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  • 1.
    Aanestad, Øystein
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Quantitative electromyographic studies of the perineal muscles in normal subjects and patients suffering from anal or urinary incontinence1998Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The aims of the study were to characterize the interference pattern in perineal muscles in healthy subjects with the use of quantitative EMG techniques, to evaluate if prostatic surgery had any effect on the interference pattern and furthermore to examine the interference pattern in the perineal muscles in patients suffering from urinary or anal incontinence.

    The interference pattern in the perineal muscles was examined with a computerized analysis, the Turns and Amplitude (T/A) analysis, and the innervation pattern of the muscles was examined with single fiber electromyography measuring the fiber density. Reference values were collected from 30 normal subjects. The patient material consisted of 20 males subjected to transurethral prostatectomy (TUR-P), 10 males who underwent radical retropubic prostatectomy (RRP), 20 patients suffering from anal incontinence and 24 women withurinary incontinence.

    T/A analysis of the interference pattern in the perineal muscles in normal subjects showed a significant increase in number of turns/sec and mean amplitude correlating to increasing force but no age-related changes.

    TUR-P and RRP did effect the innervation of the distal urethral sphincter muscle as shown by increased fiber density indicating a peripheral nerve lesion. T/A analysis did not shown any increased activation of the distal urethral sphincter as a compensation for the loss in bladder neck sphincter function but rather signs of decreasedcentral activation.

    Patients with idiopathic faecal incontinence showed signs of impaired innervation of the external anal sphincter muscle. A decreased interference pattern at maximal contraction indicated a reduced central activation of perineal muscles, in particular for patients with partial rupture of the external anal sphincter muscle. The reduced central activation could play a role for the aetiology of faecal incontinence.

    Patients with urinary stress incontinence also showed signs of impaired innervation of the external anal sphincter muscle as well as reduced interference pattern at maximal contraction and during continuous recording of the EMG activity during cystometry. A reduced central activation of the motor units was predicted as one factor involved in the aetiology.

  • 2.
    Aarts, Clara
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Exclusive breastfeeding-Does it make a difference?: A longitudinal, prospective study of daily feeding practices, health and growth in a sample of Swedish infants2001Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The concept of exclusive breastfeeding in relation to daily feeding practices and to health and growth of infants in an affluent society was examined. In a descriptive longitudinal prospective study 506 mother-infant pairs were followed from birth through the greater part of the first year. Feeding was recorded daily, and health and growth were recorded fortnightly.

    Large individual variations were seen in breastfeeding patterns. A wide discrepancy between the exclusive breastfeeding rates obtained from "current status" data and data "since birth" was found.

    Using a strict definition of exclusive breastfeeding from birth and taking into account the reasons for giving complementary feeding, the study showed that many exclusively breastfed infants had infections early in life, the incidence of which increased with age, despite continuation of exclusive breastfeeding. However, truly exclusively breastfed infants seem less likely to suffer infections than infants who receive formula in addition to breast milk. Increasing formula use was associated with an increasing likelihood of suffering respiratory illnesses. The growth of exclusively breastfed infants was similar to that of infants who were not exclusively breastfed.

    The health of newborn infants during the first year of life was associated with factors other than feeding practices alone. Some of these factors may be prenatal, since increasing birth weight was associated with an increasing likelihood of having respiratory symptoms, even in exclusively breastfed infants. However, exclusive breastfeeding was shown to be beneficial for the health of the infant even in an affluent society.

    Fulltekst (pdf)
    FULLTEXT01
  • 3.
    Acosta, Stefan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    On Acute Thrombo-Embolic Occlusion of the Superior Mesenteric Artery2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) with intestinal infarction is a lethal disease, difficult to diagnose in time, with unknown incidence and cause-specific mortality. The aim of this thesis was to characterize the disease and to develop diagnostic methods.

    Two laboratory studies were conducted on patients with suspected acute SMA occlusion. A pilot-study showed that the fibrinolytic marker D-dimer was elevated in six patients with the disease. In the subsequent study including 101 patients, D-dimer was the only elevated coagulation marker in nine patients with the disease. In a prospective study 24 patients (median age 84 years) were identified, of whom four were diagnosed at autopsy, despite an autopsy-rate of 10%. One-fourth were initially nursed in non-surgical wards. Length of the intestinal infarction was a predictor for death. An analysis of patients from the three studies showed that D-Dimer was elevated in all 16 tested patients with the disease.

    Sixty patients with acute SMA occlusion underwent intestinal revascularisation and were registered in the Swedish Vascular Registry (SWEDVASC). One-year survival-rate was 40%. Previous vascular surgery was a negative risk-factor.

    A population-based study was conducted in Malmö, based on an autopsy-rate of 87%. Among 270 patients with the disease, 2/3 were diagnosed only at autopsy and 1/2 were managed in non-surgical wards. The incidence was 8.6 per 100000 person years. The age-standardized incidence increased exponentially without gender differences. The diagnosis was the cause of death in 1.2% among octogenarians and beyond. Thrombotic occlusions were located proximally within the SMA and associated with extensive intestinal infarctions. Synchronous embolism, often multiple, occurred in 2/3 of the patients with embolic occlusions.

    Conclusions: A normal D-dimer at presentation most likely excludes the diagnosis. Acute SMA occlusion was more frequent than previously estimated from clinical series. The patients were often nursed in non-surgical wards.

    Delarbeid
    1. Preliminary study of D-dimer as a possible marker of acute bowel ischaemia
    Åpne denne publikasjonen i ny fane eller vindu >>Preliminary study of D-dimer as a possible marker of acute bowel ischaemia
    2001 Inngår i: Br J Surg, Vol. 88, s. 385 - 388Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91561 (URN)
    Tilgjengelig fra: 2004-04-14 Laget: 2004-04-14bibliografisk kontrollert
    2. D-dimer testing in patients with suspected acute thromboembolic occlusion of the superior mesenteric artery
    Åpne denne publikasjonen i ny fane eller vindu >>D-dimer testing in patients with suspected acute thromboembolic occlusion of the superior mesenteric artery
    2004 (engelsk)Inngår i: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 91, nr 8, s. 991-994Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND:

    There is no accurate non-invasive method available for the diagnosis of acute thromboembolic occlusion of the superior mesenteric artery (SMA). The aim of this study was to assess the diagnostic properties of the fibrinolytic marker D-dimer.

    METHODS:

    From September 2000 to April 2003 consecutive patients aged over 50 years admitted to hospital with acute abdominal pain were studied. Patients with possible acute SMA occlusion at presentation had blood samples taken within 24 h of the onset of the pain for analysis of D-dimer, plasma fibrinogen, activated partial thromboplastin time, prothrombin time and antithrombin. The value of D-dimer testing to diagnose SMA occlusion was assessed by means of likelihood ratios.

    RESULTS:

    Nine of 101 patients included had acute SMA occlusion. The median D-dimer concentration was 1.6 (range 0.4-5.6) mg/l, which was higher than that in 25 patients with inflammatory disease (P = 0.007) or in 14 patients with intestinal obstruction (P = 0.005). The combination of a D-dimer level greater than 1.5 mg/l, atrial fibrillation and female sex resulted in a likelihood ratio for acute SMA occlusion of 17.5, whereas no patient with a D-dimer concentration of 0.3 mg/l or less had acute SMA occlusion.

    CONCLUSION:

    D-dimer testing may be useful for the exclusion of patients with suspected acute SMA occlusion.

    Emneord
    Abdominal Pain/*etiology, Aged, Aged; 80 and over, Female, Fibrin Fibrinogen Degradation Products/*analysis, Humans, Male, Mesenteric Artery; Superior, Mesenteric Vascular Occlusion/*diagnosis, Middle Aged, Sensitivity and Specificity, Thromboembolism/*diagnosis
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-91562 (URN)10.1002/bjs.4645 (DOI)15286959 (PubMedID)
    Tilgjengelig fra: 2004-04-14 Laget: 2004-04-14 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    3. Acute thrombo-embolic occlusion of the superior mesenteric artery: A prospective study in a well defined population
    Åpne denne publikasjonen i ny fane eller vindu >>Acute thrombo-embolic occlusion of the superior mesenteric artery: A prospective study in a well defined population
    2003 Inngår i: Eur J Vasc Endovasc Surg, Vol. 26, s. 179-183Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91563 (URN)
    Tilgjengelig fra: 2004-04-14 Laget: 2004-04-14bibliografisk kontrollert
    4. Revascularization of the superior mesenteric artery after acute thromboembolic occlusion
    Åpne denne publikasjonen i ny fane eller vindu >>Revascularization of the superior mesenteric artery after acute thromboembolic occlusion
    Vise andre…
    2002 Inngår i: Br J Surg, Vol. 89, s. 923-927Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91564 (URN)
    Tilgjengelig fra: 2004-04-14 Laget: 2004-04-14bibliografisk kontrollert
    5. Incidence of acute thrombo-embolic occlusion of the superior mesenteric artery - a population-based study
    Åpne denne publikasjonen i ny fane eller vindu >>Incidence of acute thrombo-embolic occlusion of the superior mesenteric artery - a population-based study
    Vise andre…
    2004 Inngår i: Eur J Vasc Endovasc Surg, Vol. 27, s. 145 - 150Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91565 (URN)
    Tilgjengelig fra: 2004-04-14 Laget: 2004-04-14bibliografisk kontrollert
    6. Autopsy findings in 213 patients with fatal acute thrombo-embolic occlusion of the superior mesenteric artery
    Åpne denne publikasjonen i ny fane eller vindu >>Autopsy findings in 213 patients with fatal acute thrombo-embolic occlusion of the superior mesenteric artery
    Vise andre…
    (engelsk)Artikkel i tidsskrift (Fagfellevurdert) Submitted
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-91566 (URN)
    Tilgjengelig fra: 2004-04-14 Laget: 2004-04-14 Sist oppdatert: 2013-08-14bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 4.
    Adalberth, Gunnar
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Total knee arthroplasty: Alternative aspects on fixation, design and postoperative treatment2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Total knee arthroplasty as a treatment of severe gonarthrosis has become a great success, but tibial component loosening is still a major reason for failure. When total knee arthroplasty was introduced, only all-polyethylene (AP) tibial components were available. Based on mostly theoretical data, AP components were more or less abandoned during the 1980:ies in favor of metal-backed (MB) tibial components. The aim of the present study was to evaluate whether insufficient fixation would result, using an all-polyethylene tibial component instead of a more costly metal-backed prosthesis. Further, to compare different antibiotic loaded bone cements, and to investigate whether post- operative drainage is beneficial in total knee arthroplasty. Radiostereometric analysis (RSA) was used to obtain accurate and standardized evaluations facilitating comparison between prosthetic designs.

    Magnitude and pattern of migration of a moderately conforming AP tibial component was analyzed in 22 patients. Migration was on par with a more conforming previously used frequently, AP component, indicating a favorable prognosis regarding future aseptic loosening. Another 34 arthroplasties with a flat on flat (non-conforming) articulating geometry were randomized to an AP or MB cemented tibial component. There were no differences in migration between the groups. None of the AP implants displayed any continuous migration between 1 and 2 years postoperative. In a similar randomized series of 38 arthroplasties with a semiconstrained articulation, fixation measured with RSA was not inferior for AP implants compared with MB. Both studies indicate a good long-term prognosis using an AP component. A new antibiotic loaded bone cement was prospectively randomized against a more commonly used bone cement in a series of 51 arthroplasties. Neither fixation of the tibial component nor the radiographic and clinical results differed between the cements, indicating a good prognosis for the new cement. Postoperative drainage of knee arthroplasty is widely used. 90 patients were prospectively randomized into three groups: no drain, ordinary drain system and a retransfusable drain system. Postoperative drainage in knee arthroplasty has no adverse clinical consequences but seems not to be necessary.

  • 5.
    Adamiak, Grazyna Teresa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Hälso- och sjukvårdsforskning.
    Påverkan av organisatoriska och miljömässiga faktorer på tillgänglighet till akutsjukvården2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The settings investigated were departments of internal medicine (IM), orthopaedics and surgery in acute care hospitals in Sweden. The objective was to identify exogenous and endogenous determinants of accessibility of health care. Both qualitative and quantitative analysis of utilisation was performed on national and regional level of data aggregation. The study proposes that accessibility to acute health services is influenced by exogenous factors, partly outside the control of health care professionals, such as season, physical proximity and overall supply. Organisational properties such as availability of inpatient beds, hospital and physician specialisation and the degree of system integration between provides of emergency care have effects on the quality of care. The novel finding is the strong association between acute readmissions and remaining inpatient utilisation indicating effects of bed supply on global use within IM. These conclusions follow:

    § structural changes on system level work as a method of prioritisation between patient groups by changes in criteria of accessibility;

    § the natural and organisational environments determine waiting times in EDs in hospitals by fluctuations of demand;

    § geographical accessibility coincides with the supply in terms of over- or underutilisation mirrored in the outcome of medical care;

    § effective access is determined by the divide of resources between inpatient and outpatient care and the total supply of inpatient care;

    § increasing demands on inpatient care in IM may be derived from deficiencies in the care of chronically ill, elderly patients;

    § transition of information and communication among care givers and patients varies in efficiency depending on vehicles for coordination and system integration;

    § the level of training of the admitting physician has effects on effective accessibility to inpatient care.

    There are conflicts between accessibility, efficiency and appropriateness of settings calling for attention to capacity to benefit in addition to needs as priority criteria.

    Delarbeid
    1. Integrated care for the elderly.: The background and effects of the reform of Swedish care of the elderly.
    Åpne denne publikasjonen i ny fane eller vindu >>Integrated care for the elderly.: The background and effects of the reform of Swedish care of the elderly.
    2000 Inngår i: International Journal of Integrated Care, ISSN 1568-4156, nr 1Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91354 (URN)
    Tilgjengelig fra: 2004-02-13 Laget: 2004-02-13bibliografisk kontrollert
    2. Lack of inegration and seasonal variation in demand explained performance problems and waiting times for patients at emergency departments: A 3 years evaluation of the shift of responsibility between primary and secondary care by closure of two acute hospitals
    Åpne denne publikasjonen i ny fane eller vindu >>Lack of inegration and seasonal variation in demand explained performance problems and waiting times for patients at emergency departments: A 3 years evaluation of the shift of responsibility between primary and secondary care by closure of two acute hospitals
    2001 Inngår i: Health Policy, Vol. 55, s. 187-207Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91355 (URN)
    Tilgjengelig fra: 2004-02-13 Laget: 2004-02-13bibliografisk kontrollert
    3. Impact of proximity and hospital specialisation on appropriateness of emergency readmissions
    Åpne denne publikasjonen i ny fane eller vindu >>Impact of proximity and hospital specialisation on appropriateness of emergency readmissions
    (engelsk)Inngår i: Journal of Evaluation in Clinical PracticeArtikkel i tidsskrift (Fagfellevurdert) Accepted
    Identifikatorer
    urn:nbn:se:uu:diva-91356 (URN)
    Tilgjengelig fra: 2004-02-13 Laget: 2004-02-13 Sist oppdatert: 2010-05-24bibliografisk kontrollert
    4. Situation in Sweden
    Åpne denne publikasjonen i ny fane eller vindu >>Situation in Sweden
    2003 Inngår i: Integrated Care in Europe.: Description and comparison of integrated care in six EU countries., 2003, s. 41-68Kapittel i bok, del av antologi (Annet vitenskapelig) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91357 (URN)90 352 2605-4 (ISBN)
    Tilgjengelig fra: 2004-02-13 Laget: 2004-02-13bibliografisk kontrollert
    5. The impact of physician training level on emergency readmissions within internal medicine
    Åpne denne publikasjonen i ny fane eller vindu >>The impact of physician training level on emergency readmissions within internal medicine
    2004 (engelsk)Inngår i: International Journal of Technology Assessment in Health Care, ISSN 0266-4623, E-ISSN 1471-6348, Vol. 20, nr 4, s. 516-23Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objectives: The research question was whether training level of admitting physicians and referrals from practitioners in primary health care (PHC) are risk factors for emergency readmission within 30 days to internal medicine.

    Methods: This report is a prospective multicenter study carried out during 1 month in 1997 in seven departments of internal medicine in the County of Stockholm, Sweden. Two of the units were at university hospitals, three at county hospitals and two in district hospitals. The study area is metropolitan–suburban with 1,762,924 residents. Data were analyzed by multiple logistic regression.

    Results: A total of 5,131 admissions, thereby 408 unplanned readmissions (8 percent) were registered (69.8 percent of 7,348 true inpatient episodes). The risk of emergency readmission increased with patient's age and independently 1.40 times (95 percent confidence interval [CI], 1.13–1.74) when residents decided on hospitalization. Congestive heart failure as primary or comorbid condition was the main reason for unplanned readmission. Referrals from PHC were associated with risk decrease (odds ratio, 0.53; 95 percent CI, 0.38–0.73).

    Conclusion: The causes of unplanned hospital readmissions are mixed. Patient contact with primary health care appears to reduce the recurrence. In addition to the diagnoses of cardiac failure, training level of admitting physicians in emergency departments was an independent risk factor for early readmission. Our conclusion is that it is cost-effective to have all decisions on admission to hospital care confirmed by senior doctors. Inappropriate selection of patients to inpatient care contributes to poor patient outcomes and reduces cost-effectiveness and quality of care.

    Emneord
    Emergency readmission; Clinical experience; Training level; Internal medicine; Referrals.
    Identifikatorer
    urn:nbn:se:uu:diva-91358 (URN)10.1017/S0266462304001448 (DOI)
    Tilgjengelig fra: 2004-02-13 Laget: 2004-02-13 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 6.
    Afrakhte, Mozhgan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Growth control mechanisms in normal and neoplastic mammalian cells1998Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The main theme of the studies presented in this thesis is, the growth control mechanisms whose loss in normal cells predispose to or cause cancer. The balance between growth inhibitory and stimulatory mechanisms is crucial for the development and maintenance of a normal animal.

    PDGF, a growth factor for cells of mesenchymal origin, is implicated in normal developmental processes as well as neoplasia. The alternative splicing of exon 6 in PDGF-A gene transcripts gives rise to two different proteins with different compartmentalization properties. The PDGF-A chain homodimers, PDGF-AAL, encoded PDGF A-splice variant remain associated with the cell membrane. Studies of a human fibrosarcoma cell line, U-2197, revealed a high expression level of the cell associated PDGF-AAL which upon release increased autophosphorylation of the endogenous PDGF receptors, suggesting an autocrine loop. PDGF-A gene and PDGFR-α gene found to be co-amplified in the U-2197, indicating an optimised system for growth in these cells, i.e. amplified growth factor receptor as well as a local autocrine supply of the mitogen.

    Members of TGFβ superfamily are potent regulators of the growth and differentiation of a wide range of cell types. Intracellular mediators of TGF-β signalling, SMADs, transduce signals from serine/threonine kinase receptors to the nucleus where they affect transcription of target genes. A new class of SMAD proteins has been identified whose members, the inhibitory SMADS, antagonise TGF-β signals by interfering with agonistic SMADs activity. Smad6 and Smad7 are two closely related TGF-β antagonists identified in mammalian cells. Overexpression of Smad7 inhibited the cellular response to TGF-β whereas expression of an anti-sense Smad7 construct showed an enhancing effect on this response. The inhibitory SMADs may act in a negative feedback loop, as their expression is induced by the same ligands whose action they antagonise.

    Density dependent growth inhibition is a growth control mechanism often lost in transformed and malignant cells. Cells in dense culture are refractory to the mitogen stimulation although, the mitogenic signals were shown to be processed to some extent. The expression of immediate-early genes in dense culture stimulated with mitogen was induced. The activity of cyclin dependent kinases (CDKs), the pivotal kinases in G1/S transition, showed to be density dependent and decreased by increasing cell density. pRb, a tumour suppressor and growth regulatory protein, remained unphosphorylated in mitogen treated dense culture. The cessation of CDKs kinase activity in dense cultures was shown to be accompanied with increasing expression of inhibitory proteins of these kinases, CKIs. The impaired expression of a positive regulator of CDKs, Cdc25A phosphatase, was another feature of dense cultures.

  • 7.
    Agréus, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    The abdominal symptom study: an epidemiological survey of gastrointestinal and other abdominal symptoms in the adult population of Östhammar, Sweden1993Doktoravhandling, med artikler (Annet vitenskapelig)
  • 8.
    Ahlgren, Johan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Studies on Prediction of Axillary Lymph Node Status in Invasive Breast Cancer2002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Breast cancer is the most common malignancy among females in Sweden. Axillary lymph-node dissection is a standard procedure in the management of breast cancer, aiming at obtaining prognostic information for adjuvant therapy decisions. Axillary dissection entails considerable morbidity. The aims of this study were to establish more selective surgical approaches and to investigate angiogenesis, a potential predictor for lymph-node metastases and prognosis.

    Clinical nodal status, tumour size and S-phase were associated with nodal metastases in cohort of 1145 women. The proportion of nodal metastases was 13% in the subgroup with the lowest risk.

    In a study from two registries, 675 and 1035 breast cancers ≤10 mm diagnosed by screening mammography had nodal metastases in 6,5% and 7%, respectively. Clinically detected cancers had a risk of 16% and 14%, respectively.

    In a study on 415 women, a 5-node biopsy of the axilla had a sensitivity of 97,3% and a false negative rate of 2,7% in comparison with axillary dissection.

    Six sections from 21 breast cancers were analysed for microvessel density (MVD). The inter-section variation contributed more to the total variance than inter-tumour variation, 45,0% and 37,3%, respectively.

    In a cohort of 315 women, breast cancers with high MVD more frequently had p53 mutations (27,1%) compared with cases with low MVD (18,4%). This difference was not statistically significant (p=0,075). p53 mutations were associated with a worse outcome, whereas MVD was not.

    In conclusion, women with screening detected ≤10 mm breast cancers have a low risk of lymph node metastases and some may not need axillary dissection in the future. The 5-node biopsy could be an alternative to axillary dissection. MVD is associated with methodological weaknesses and routine use is not recommended.

    Fulltekst (pdf)
    FULLTEXT01
  • 9.
    Ahlström, Gerd
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Consequences of muscular dystrophy: impairment, disability, coping and quality of life1994Doktoravhandling, med artikler (Annet vitenskapelig)
  • 10.
    Ahmad, Abdulbaghi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Childhood trauma and posttraumatic stress disorder: A developmental and cross-cultural approach1999Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis aims to identify child-specific cross-cultural protecting and vulnerability factors regarding traumatic experiences and posttraumatic stress reactions. Children between 6-18 years were interviewed from three different socio-cultural backgrounds. In Iraqi Kurdistan, 20 participants in a mass-escape tragedy (MET), 54 orphans and 45 survivors of the genocide operation "Anfal" were interviewed. In Sweden, a sample of 32 Kurdistanian refugee children and a comparable Swedish sample were included. The frequencies of posttraumatic stress disorder (PTSD) were 20%, 43%. 87%, 9,7% and 12.5% respectively.

    The relatively low frequencies of PTSD in the follow-up sample 2 months, 4 months, 14 months and 26 months after the MET suggest the child functioning in a complete, authoritative family, as a protecting factor. The significant of this developmentally based child-specific functioning level within the supportive family system can also explain the fluctuating PTSD-related symptom scores in this sample parallel to the changes in the socio-economic situation in the region. The over time decrease in behavioural problems among fostercare orphans and their low PTSD frequencies as compared with the increase in behavioural problems and the high PTSD frequencies among orphanage samples further support this suggestion. Child trauma scores and captivity duration predicted for PTSD in "Anfal" survivors, irrespective of parents' trauma scores and PTSD or fathers re-union with the family, suggesting child-specific vulnerability more than contagion effect. Despite PTSD, children in Kurdistan performed high functioning levels, probably indicating a child-specific manifestation of hypervigilance. The Kurdistanian refugee sample revealed lower lifetime reexperiencing PTSD symptom scores than the Swedish sample, indicating a healing effect on the former coming to Sweden and a resilience deficit for the later growing up in a highly sheltered society.

    There are more similarities than differences between children from Kurdistan and Sweden in reporting traumatic experiences and exhibiting posttraumatic stress symptoms. Developmentally based child characteristics have a determinant role as protective or vulnerability factors in childhood trauma and PTSD, even if socio-cultural factors also play a role.

  • 11.
    Ahmad, Abdulbaghi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Childhood trauma and posttraumatic stress disorder: A developmental and cross-cultural approach1999Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis aims to identify child-specific cross-cultural protecting and vulnerability factors regarding traumatic experiences and posttraumatic stress reactions. Children between 6-18 years were interviewed from three different socio-cultural backgrounds. In Iraqi Kurdistan, 20 participants in a mass-escape tragedy (MET), 54 orphans and 45 survivors of the genocide operation "Anfal" were interviewed. In Sweden, a sample of 32 Kurdistanian refugee children and a comparable Swedish sample were included. The frequencies of posttraumatic stress disorder (PTSD) were 20%, 43%. 87%, 9,7% and 12.5% respectively.

    The relatively low frequencies of PTSD in the follow-up sample 2 months, 4 months, 14 months and 26 months after the MET suggest the child functioning in a complete, authoritative family, as a protecting factor. The significant of this developmentally based child-specific functioning level within the supportive family system can also explain the fluctuating PTSD-related symptom scores in this sample parallel to the changes in the socio-economic situation in the region. The over time decrease in behavioural problems among fostercare orphans and their low PTSD frequencies as compared with the increase in behavioural problems and the high PTSD frequencies among orphanage samples further support this suggestion. Child trauma scores and captivity duration predicted for PTSD in "Anfal" survivors, irrespective of parents' trauma scores and PTSD or fathers re-union with the family, suggesting child-specific vulnerability more than contagion effect. Despite PTSD, children in Kurdistan performed high functioning levels, probably indicating a child-specific manifestation of hypervigilance. The Kurdistanian refugee sample revealed lower lifetime reexperiencing PTSD symptom scores than the Swedish sample, indicating a healing effect on the former coming to Sweden and a resilience deficit for the later growing up in a highly sheltered society.

    There are more similarities than differences between children from Kurdistan and Sweden in reporting traumatic experiences and exhibiting posttraumatic stress symptoms. Developmentally based child characteristics have a determinant role as protective or vulnerability factors in childhood trauma and PTSD, even if socio-cultural factors also play a role.

    Delarbeid
    1. Symptoms of post-traumatic stress disorder among displaced Kurdish children in Iraq; victims of a man-made disaster after the Gulf war.
    Åpne denne publikasjonen i ny fane eller vindu >>Symptoms of post-traumatic stress disorder among displaced Kurdish children in Iraq; victims of a man-made disaster after the Gulf war.
    1992 (engelsk)Inngår i: Nordic Journal Psychiatry, Vol. 46, nr 5, s. 315-319Artikkel i tidsskrift (Fagfellevurdert) Published
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-26241 (URN)
    Tilgjengelig fra: 2007-02-15 Laget: 2007-02-15 Sist oppdatert: 2020-03-10
    2. The socioemotional development of orphans in orphanages and traditional foster care in Iraqi Kurdistan
    Åpne denne publikasjonen i ny fane eller vindu >>The socioemotional development of orphans in orphanages and traditional foster care in Iraqi Kurdistan
    1996 (engelsk)Inngår i: Child Abuse & Neglect, Vol. 20, s. 1161-Artikkel i tidsskrift (Fagfellevurdert) Published
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-55922 (URN)
    Tilgjengelig fra: 2008-10-17 Laget: 2008-10-17 Sist oppdatert: 2020-03-10
    3. A 26-month follow-up of posttraumatic stress symptoms in children after the mass-escape tragedy in Iraqi Kurdistan
    Åpne denne publikasjonen i ny fane eller vindu >>A 26-month follow-up of posttraumatic stress symptoms in children after the mass-escape tragedy in Iraqi Kurdistan
    1998 (engelsk)Inngår i: Nord J Psychiatry, Vol. 52, s. 357-Artikkel i tidsskrift (Fagfellevurdert) Published
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-56716 (URN)
    Tilgjengelig fra: 2008-10-17 Laget: 2008-10-17 Sist oppdatert: 2020-03-10
    4. Reliability and validity of a child-specific cross-cultural instrument for assessing posttraumatic stress disorder
    Åpne denne publikasjonen i ny fane eller vindu >>Reliability and validity of a child-specific cross-cultural instrument for assessing posttraumatic stress disorder
    Vise andre…
    2000 (engelsk)Inngår i: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 9, nr 4, s. 285-294Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The Posttraumatic Stress Symptoms in Children (PTSS-C) was developed as a cross-cultural semi-structured interview to diagnose posttraumatic stress disorder (PTSD) and to identify PTSD-non-related posttraumatic stress symptoms in children after various traumatic experiences. The psychometric properties were studied in two different child populations in Iraqi Kurdistan (the survivors of the military operation “Anfal”, and the orphans), in a sample of Kurdistanian refugee children in Sweden, and in a comparison sample of Swedish children. The instrument yielded satisfactory internal consistency, high interrater agreement, and excellent validity on cross-validation with the Child Posttraumatic Stress Disorder Reaction Index (CPTSD-RI) and the Diagnostic Interview for Children and Adolescents (DICA) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-56320 (URN)10.1007/s007870070032 (DOI)
    Tilgjengelig fra: 2008-10-17 Laget: 2008-10-17 Sist oppdatert: 2020-03-10bibliografisk kontrollert
    5. Posttraumatic stress disorder in children after the military operation "Anfal" in Iraqi Kurdistan
    Åpne denne publikasjonen i ny fane eller vindu >>Posttraumatic stress disorder in children after the military operation "Anfal" in Iraqi Kurdistan
    2000 (engelsk)Inngår i: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 9, nr 4, s. 235-243Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

     Five years after the military operation “Anfal” in Iraqi Kurdistan, 45 families were randomly selected among the survivors in two displacement camps. The Posttraumatic Stress Symptoms for Children (PTSS-C) and the Harvard Trauma Questionnaire (HTQ) were administered to the oldest child and the caregiver in each family, respectively. Posttraumatic stress disorder (PTSD) was reported in 87% of children and 60% of their caregivers. While childhood PTSD was only significantly predicted by child trauma score and the duration of captivity, it was neither predicted by maternal PTSD nor did it disappear after the reunion with the PTSD-free father. However, the small sample size makes the results hypotheses rather than conclusive.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-56319 (URN)10.1007/s007870070026 (DOI)
    Tilgjengelig fra: 2008-10-17 Laget: 2008-10-17 Sist oppdatert: 2020-03-10bibliografisk kontrollert
  • 12.
    Ahmed, Meftun
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Oscillatory Ca2+ signaling in glucose-stimulated murine pancreatic β-cells: Modulation by amino acids, glucagon, caffeine and ryanodine2001Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Oscillations in cytoplasmic Ca2+ concentration ([Ca2+]i) is the key signal in glucose-stimulated β-cells governing pulsatile insulin release. The glucose response of mouse β-cells is often manifested as slow oscillations and rapid transients of [Ca2+] i. In the present study, microfluorometric technique was used to evaluate the role of amino acids, glucagon, ryanodine and caffeine on the generation and maintenance of [Ca2+] i oscillations and transients in individual murine β-cells and isolated mouse pancreatic islets. The amino acids glycine, alanine and arginine, at around their physiological concentrations, transformed the glucose-induced slow oscillations of [Ca2+] i in isolated mouse β-cells into sustained elevation. Increased Ca2+ entry promoted the reappearance of the slow [Ca2+] i oscillations. The [Ca2+] i oscillations were more resistant to amino acid transformation in intact islets, supporting the idea that cellular interactions are important for maintaining the oscillatory activity. Individual rat β-cells responded to glucose stimulation with slow [Ca2+] i oscillations due to periodic entry of Ca2+ as well as with transients evoked by mobilization of intracellular stores. The [Ca2+] i oscillations in rat β-cells had a slightly lower frequency than those in mouse β-cells and were more easily transformed into sustained elevation in the presence of glucagon or caffeine. The transients of [Ca2+] i were more common in rat than in mouse β-cells and often appeared in synchrony also in cells lacking physical contact. Depolarization enhanced the generation of [Ca2+] i transients. In accordance with the idea that β-cells have functionally active ryanodine receptors, it was found that ryanodine sometimes restored oscillatory activity abolished by caffeine. However, the IP3 receptors are the major Ca2+ release channels both in β-cells from rats and mice. Single β-cells from ob/ob mice did not differ from those of lean controls with regard to frequency, amplitudes and half-widths of the slow [Ca2+] i oscillations. Nevertheless, there was an excessive firing of [Ca2+] i transients in the β-cells from the ob/ob mice, which was suppressed by leptin at close to physiological concentrations. The enhanced firing of [Ca2+] i transients in ob/ob mouse β-cells may be due to the absence of leptin and mediated by activation of the phospholipase C signaling pathway.

    Fulltekst (pdf)
    FULLTEXT01
  • 13.
    Ahn, Chul Min
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Thrombin-induced pulmonary injury in the rat: role of neutrophil elastase and arachidonic acid metabolites1996Doktoravhandling, med artikler (Annet vitenskapelig)
  • 14.
    Ahrenstedt, Örjan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Immunologic characterization of Crohn's disease by segmental intestinal perfusion1991Doktoravhandling, med artikler (Annet vitenskapelig)
  • 15.
    Akyürek, M. Levent
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Transplant arteriosclerosis: experimental studies in the rat1996Doktoravhandling, med artikler (Annet vitenskapelig)
  • 16.
    Albinsson, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    A Palliative Approach to Dementia Care: Leadership and organisation, existential issues and family support2002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The main purpose of this thesis was to apply the WHO and NHS palliative care approach to dementia care.

    Thirty-one staff-members in mid-Sweden (studies I and II) and 20 next-of- kin (study IV) were interviewed. In study III, 316 staff-members from dementia care and 121 staff-members from palliative cancer care responded to a questionnaire about family support. The interviews were tape-recorded and analysed with a qualitative phenomenographic (I and II) and a hermeneutic approach (IV). The questionnaires (III) were analysed using qualitative and quantitative content analysis.

    The staff-members stated almost unanimously that daily leadership was lacking, and consequently clear goal formulations and care planning were rare (I). Proper teamwork between the doctor and the staff who worked on a daily basis with the patients was absent (I). With respect to existential issues, education and staff discussions were lacking (II). The staff were at a loss concerning how to deal with these issues. Nevertheless, these issues are central to family-members who have to deal with an existential crisis (IV). Important questions emerged about obligation and guilt, faithfulness, responsibility, and paying back what you once received. Existential isolation could be identified e.g. in the reversal of roles experienced as "being a parent to your parent" and in the burden of "visiting a living dead person".

    There were no routines for bereavement visits. The type of support suggested for dementia family members is partly similar to support in palliative cancer care, but it also differs in other respects such as feelings of guilt because the early signs of the disease are misunderstood, the need for respite because of the long trajectory of dementia diseases, and the occurrence of anticipatory grief because in the late phase family members can no longer make any contact at all with the patient (III).

    A palliative approach can improve the quality of life for the dementia patient and for the family. It can be used as a basis for a clear goal formulation. Some of the suggestions listed in this thesis for improving the quality of care are more a reflection of the need for a change in attitudes rather than the need for substantial budget increases.

    Fulltekst (pdf)
    FULLTEXT01
  • 17.
    Alderborn, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    On the switch from a latent to an amplification mode of plasmid DNA replication of a papillomavirus1994Doktoravhandling, med artikler (Annet vitenskapelig)
  • 18.
    Alemi, Mansour
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Molecular biological techniques as a tool in diagnostic pathology: Applications in B-cell lymphoproliferative disease, medullary thyroid carcinoma and cervical carcinoma2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Identification of malignancy associated with mutations in gene sequences requires detection ofas little as a single base difference. A powerful technique in mutation detection is polymerasechain reaction (PCR) followed by single-strand conformational polymorphism (SSCP) andsequencing.

    The present investigation is focused on improving tests for the following diagnostic questions:(i) clonality in malignancy of lymphoid origin by developing simple laboratory methodsbased on PCR in which the monoclonal B-cell lineage can be distinguished from thepolyclonal, (ii) presence of mutations in RET proto-oncogene involved in sporadic medullarythyroid carcinoma (MTC), and (iii) development of a simple test which can distinguishbetween prototype human papillomavirus 16 (HPV16) and variant HPV16 containing a pointmutation at codon 83 of the E6 gene.

    The rearrangement of the immunoglobulin heavy chain gene can be used as a marker of B-celllineage and clonality. By using PCR with specific primers corresponding to the variable and joining regions, it is possible to detect the rearrangement of a small amount of clonal B-cells ina polyclonal background. This study has shown that the SSCP analysis of PCR fragmentsincreases the sensitivity and the specificity of the test.

    Oncogenic activation of the RET related to somatic missense mutations has been shown insporadic MTC. These mutations are believed to play an important role in the tumorigenesis ofMTC. By combining microdissection of tumor cells followed by PCR-SSCP, fragment sizeanalysis and sequencing, a small proportion of cells with mutation in a subpopulation of cellswithin a tumor can be detected. A variant of HPV 16 has previously been shown to be moreprevalent in invasive cervical carcinoma than in preinvasive lesions. In the present study asimple, rapid PCR-SSCP assay has been developed to identify women who are at increasedrisk of progression to invasive cervical carcinoma.

  • 19.
    Ali, Liaquat
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Effects of glucose and sulfonylureas on sodium in pancreatic islets1990Doktoravhandling, med artikler (Annet vitenskapelig)
  • 20.
    Allen, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Genetic typing of HLA polymorphism: application to studies of disease association and forensic medicine1995Doktoravhandling, med artikler (Annet vitenskapelig)
  • 21.
    Almegård, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Studies on iris sphincter and ciliary muscle contraction in primates: effects of cholecystokinin and other sensory neuropeptides1993Doktoravhandling, med artikler (Annet vitenskapelig)
  • 22.
    Almgren, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Nonthrombotic deep venous incompetence: with special reference to anatomic, hemodynamic and therapeutic aspects1990Doktoravhandling, med artikler (Annet vitenskapelig)
  • 23.
    Alston-Smith, James
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Hepatic extraction and synthesis of hyaluronan in endotoxic rats1992Doktoravhandling, med artikler (Annet vitenskapelig)
  • 24.
    Althini, Susanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Experimental Studies of BMP Signalling in Neuronal Cells2003Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The developing nervous system depends largely on extracellular cues to shape its complex network of neurons. Classically, neurotrophins are known to be important mediators in this process. More recently, Bone Morphogenetic Proteins (BMPs), belonging to the Transforming Growth Factor beta (TGFβ) superfamily of secreted cytokines, have been shown to exert a wide range of effects, such as cellular growth, differentiation, survival and apoptosis, both in the developing and adult nervous system. They signal via serine/threonine kinase receptor essentially to the Smad pathway, which carries the signal to the nucleus where the transcription of target genes is regulated.

    This thesis investigates the functions of BMPs in the nervous system, using a set of different models. Firstly, a targeted deletion of GDF10 (BMP3b) in the mouse was established to evaluate the role of this growth/differentiation factor in the hippocampal formation, a brain area known to be involved in memory processing. Other members of the TGFβ superfamily likely compensate for the lack of GDF10, since no detectable alterations in hippocampal function or gene transcription profile have been found. Secondly, a mouse model was set up, with the aim to study impaired BMP-signalling in dopaminergic neurons. The tyrosine hydroxylase (TH) locus was used to drive the expression of dominant negative BMP receptors by means of bicistronic mRNAs. TH is the rate-limiting enzyme in the biosynthesis of catecholamine and the mice described, show a graded decrease of TH-activity resulting in severe to mild dopamine deficiency. The contribution of the dominant negative BMP receptors to the phenotype is however secondary to the apparent TH hypomorphism. The final theme of this thesis is the potentiating effects of BMPs on neurotrophin-induced neurite outgrowth as studied in explanted ganglia from chick embryos and in the rat phaeochromocytoma cell line PC12. A number of pharmacological inhibitors of intracellular signalling kinases were applied to the cultures in order to reveal the contribution of different pathways to the enhanced neurite outgrowth. We made the unexpected finding that inhibition of MEK signalling mimicked the potentiating effects of BMP stimulation in the chick system. The underlying mechanisms for the synergistic effects, however, are still an enigma.

    Delarbeid
    1. Targeted Deletion of GDF10 has no Effect on Long Term Potentiation, Contextual Learning Ability or Gene Transcription in the Hippocampus
    Åpne denne publikasjonen i ny fane eller vindu >>Targeted Deletion of GDF10 has no Effect on Long Term Potentiation, Contextual Learning Ability or Gene Transcription in the Hippocampus
    Vise andre…
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-90335 (URN)
    Tilgjengelig fra: 2003-04-24 Laget: 2003-04-24 Sist oppdatert: 2010-01-13bibliografisk kontrollert
    2. Normal Nigrostriatal Innervation but Dopamine Dysfunction in Mice Carrying Hypomorphic Tyrosine Hydroxylase Alleles
    Åpne denne publikasjonen i ny fane eller vindu >>Normal Nigrostriatal Innervation but Dopamine Dysfunction in Mice Carrying Hypomorphic Tyrosine Hydroxylase Alleles
    Vise andre…
    2003 (engelsk)Inngår i: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 72, nr 4, s. 444-453Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We investigated the use of the mouse tyrosine hydroxylase (TH) gene to drive knock-in constructs in catecholaminergic neurons. Two targeting constructs representing truncated forms of either of the BMP receptors ALK-2 or BMPR-II preceded by an internal ribosome entry site (IRES) were introduced into the 3' untranslated region of TH. An frt-flanked neomycin-resistance (neo(r)) cassette was placed in the 3' end of the targeting constructs. Mice homozygous for the knock-in alleles showed various degrees of hypokinetic behavior, depending mainly on whether the neo(r) cassette was removed. In situ hybridization and immunohistochemistry showed that TH mRNA and protein were variously down-regulated in these mouse strains. Reduced levels of dopamine and noradrenalin were found in several brain areas. However, number and morphology of neurons in substantia nigra and their projections to striatum appeared normal in the neo(r)-positive TH hypomorphic mice as examined by markers for L-aromatic amino acid decarboxylase and the dopamine transporter. Elimination of the neo(r) cassette from the knock-in alleles partially restored TH and dopamine levels. The present neo(r)-positive TH hypomorphic mice show that nigrostriatal innervation develops independently of TH and should find use as a model for conditions of reduced catecholamine synthesis, as seen in, for example, L-dihydroxyphenylalanine-responsive dystonia/infantile parkinsonism.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-91750 (URN)10.1002/jnr.10606 (DOI)12704806 (PubMedID)
    Merknad

    De två första författarna delar första författarskapet.

    Tilgjengelig fra: 2004-04-21 Laget: 2004-04-21 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    3. Blocked MAP kinase activity selectively enhances neurotrophic growth responses
    Åpne denne publikasjonen i ny fane eller vindu >>Blocked MAP kinase activity selectively enhances neurotrophic growth responses
    Vise andre…
    2004 (engelsk)Inngår i: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 25, nr 2, s. 345-354Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Bone morphogenetic proteins (BMPs) 4 and 6 as well as MEK inhibitors PD98059 and U0126 potentiate neurotrophin 3 (NT3)- and neurturin (NTN)-induced neurite outgrowth and survival of peripheral neurons from the E9 chicken embryo. Preexposure to BMP4 or PD98059 was sufficient to prime the potentiation of subsequently added NT3. Phosphorylation of Erk2, induced by NT3, was reduced by MEK inhibition but unaffected by BMP signaling. Real-time PCR showed that neither BMP stimulation nor MEK inhibition increased Trk receptor expression and that the BMP-induced genes Smad6 and Id1 were not upregulated by PD98059. In contrast, both MEK inhibition and BMP signaling suppressed transcription of the serum-response element (SRE)-driven Egr1 gene. A reporter assay using NGF-stimulated PC12 cells demonstrated that MEK/Erk/Elk-driven transcriptional activity was inhibited by Smad1/5 and by PD98059. Thus, suppression of SRE-controlled transcription represents a likely convergence point for pathways regulating neurotrophic responses.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-90337 (URN)10.1016/j.mcn.2003.10.015 (DOI)15019950 (PubMedID)
    Tilgjengelig fra: 2003-04-24 Laget: 2003-04-24 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    4. Bone morphogenetic protein signalling in NGF-stimulated PC12 cells
    Åpne denne publikasjonen i ny fane eller vindu >>Bone morphogenetic protein signalling in NGF-stimulated PC12 cells
    Vise andre…
    2003 (engelsk)Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 307, nr 3, s. 632-639Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Bone morphogenetic proteins (BMPs) are shown to potentiate NGF-induced neuronal differentiation in PC12 phaeochromocytoma cells grown on collagen under low-serum conditions. Whereas, cell bodies remained rounded in control medium or with only BMPs present, addition of BMP4 or BMP6 robustly increased the neuritogenic effect of NGF within 2 days. NGF-increased phosphorylation of p44(Erk1) and p42(Erk2) between 2 and 24h was unaffected by addition of BMP6. PC12 cells transfected with the SBE(4x)-luc reporter showed that BMP4 significantly increased receptor-activated Smad activity. Expression of constitutively active BMP receptor ALK2 activating Smad1 and Smad5 resulted in a strong increase in the SBE(4x)-luc reporter response. Adding the inhibitory Smad7 drastically reduced this signal. In contrast to wild-type (wt) Smad5, a Smad5 variant lacking five Erk phosphorylation sites in the linker region (designated Smad5/5SA) showed a strong background transcriptional activity. A fusion construct (Gal4-Smad5/5SA) was also highly transcriptionally active. Addition of the MEK inhibitor U0126 to PC12 cells expressing Gal4-Smad5/wt did not increase background transcriptional activity. However, upon activation by constitutively active ALK2 both Gal4-Smad5/wt and Gal4-Smad5/5SA strongly stimulated transcription. The data show that serine residues of the linker region of Smad5 reduce spontaneous transcriptional activity and that NGF-activated Erk does not antagonise BMP signalling at this site. Hence, NGF and BMP signals are likely to interact further downstream at the transcriptional level in neuronal differentiation of the PC12 cells.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-90338 (URN)10.1016/S0006-291X(03)01236-1 (DOI)12893270 (PubMedID)
    Tilgjengelig fra: 2003-04-24 Laget: 2003-04-24 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 25.
    Alting-Mees, Michelle A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Biomolecular recognition: recombinant antibodies, phage display and eukaryotic cloning systems1993Doktoravhandling, med artikler (Annet vitenskapelig)
  • 26.
    Al-Windi, Ahmad
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Determinants of health care and drug utilisation: The causes of health care utilisation study2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The costs of health care and medicines are a considerable and rapidly increasing part of the gross national product in Sweden. like in many other countries.

    The purpose of this study was to identify factors that influenced the we of health care and drugs in subjects aged 16 years and above in Håbo, a Swedish municipality. The study population consisted of 827 men and women from a random age-stratified population sample of 1,312 subjects. A postal questionnaire was used to collect information on sociodemographic characteristics. well-being variables. symptoms and chronic disease, and on the use of health care (including alternative medicine), drugs (including herbal medicines) and self-care products.

    Several sociodemographic characteristics, such as as sex, marital status, household size, educational level and occupational status, were related to many of the well-being variables and symptoms. These sociodemographic characteristic were also independently related to the use of health care. drugs and self-care products.

    Well-being variables (particularly bad perceived health), a high number of symptom (six or more) and chronic disease were also independently related to the use of health care, drugs and self-care products. Combinations of certain independent variables could explain, or "predict", special patterns of health care and drug use. For example, the likelihood of consulting a physician frequently (three times or more per year] was very high in subjects with a certain profile, viz. high age. female sex, sick leave or disability pension bad perceived health. high number of symptoms and chronic disease. Indeed, 31-92% of appointments to a physician could be attributed to these factors, depending on the model used. The same combination of factors, except high age, explained 21 to 91% of the number of patients using prescribed pharmaceuticals. Between 6% and 85% of the number of days in hospital were attributable to the combination of sick-leave or disability pension and bad perceived health, chronic disease.

    Using information on the most important variables, i.e. those with the strongest independent relationships to the use of health care and drugs. in the population of a specific district may be of value in estimating the demand for health care resources in that district. and in the allocation of resources. It may also provide a basis for preventive efforts aiming at reducing the needs.

  • 27.
    Amin, Kawa
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    The relationship between inflammation and structural changes in the airways of the lower and upper respiratory tract: Studies in patients with asthma, Sjögren's syndrome, rhinitis and children with otitis media with effusion2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The pathophysiology of asthma, Sjögrens syndrome (SS), rhinitis, and otitis media with effusion (OME) in children has been extensively investigated in upper and lower respiratory tract, respectively, and shown to comprise structural changes in the airways and involvement of inflammatory cells. By comparing diseases that have bronchial hyperresponsivenses or mucosal inflammation as a common denominator, it may be possible to learn more about the mechanisms underlying inflammation in the upper and lower respiratory tract.

    With immunohistochemical techniques and a panel of monoclonal antibodies, inflammatory cells were identified and structural changes of the airway were quantitatively studied in the bronchial, nasal and middle ear mucosa and submucosa.

    The highest number of eosinophils and mast ceils in bronchial, nasal or middle ear biopsies was found in patients with atopic asthma (AA), perennial non-allergic rhinitis (PNAR) and children with OME. The number of the neutrophils was highest in SS, non-atopic asthma (NAA) and children with OME. The number of T lymphocytes in SS and AA was significantly higher than in NAA and healthy controls (HC). The degree of epithelial damage was higher in the AA group andin patients with perennial allergic rhinitis where the biopsy was taken within the pollen season (PARSEASON) group compared to the other patient groups. The tenascin- and Iaminin-positive layers in AA and SS were thicker than other groups. In AA, and PARSEASON a significant negative correlation was found between epithelial integrity and the count for eosinophils or neutrophils. The most pronounced epithelial damage was observed in patients with allergic rhinitis in areas characterized by an increased number of inflammatory cells. Eosinophils in asthmatic and PARSEASON patients and neutrophils in SS were found in the area of epithelial damage.

    This work has demonstrated a quantitatively different inflammatory profile in AA, NAA and SS, different profiles in perennial allergic and non-allergic rhinitis and a specific inflammatory profile in the middle ear of children with OME suggesting differences in the pathogenesis of respiratory tract diseases.

  • 28.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Hodgkin Lymphoma: Studies of Advanced Stages, Relapses and the Relation to Non-Hodgkin Lymphomas2002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The relationship between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is not entirely elucidated and a clonal relation may be present more often than previously believed. Mechanisms of tumour progression and resistance to therapy are poorly understood.

    Between 1974 and 1994 all individuals in Sweden with both HL and NHL were identified. Thirty-two cases were studied using clinical, histopathological and immunohistochemical methods. The second lymphoma often appeared in an aggressive clinical form and a significant correlation between the expression of p53 and LMP-1 in the first and second lymphoma was demonstrated.

    The treatment outcome for 307 patients with advanced stages of HL, in an unselected population was in accordance with the treatment results of large centres world-wide. Some patients were successfully selected for a shorter chemotherapy-regimen without inferior treatment results.

    In 124 patients with relapse, the survival of those primarily treated with radiotherapy according to the National guidelines was in accordance with the survival of patients of initially advanced stages. A worse outcome was found for those who received both chemotherapy and radiotherapy initially, probably because of a higher frequency of bulky disease in this group.

    Immunohistochemical analysis of the tumour suppressor protein p53 and retinoblastoma protein (Rb) of paired samples at diagnosis and at relapse in 81 patients did not reveal any specific staining pattern affecting survival.

    A novel B-cell line (U-2932) was established from a patient with a diffuse large B-cell lymphoma previously treated for advanced stage and subsequent relapses of HL. An identical rearranged IgH gene was demonstrated in tumour cells from the patient and in U-2932. A p53 point mutation was detected and over-expression of the p53 protein was found. A complex karyotype with high-level amplifications of the chromosomal regions 18q21 and 3q27, i.e. the loci for bcl-2 and bcl-6 were demonstrated.

    Delarbeid
    1. Patients suffering from both Hodgkin's disease and non-Hodgkin's lymphoma: a clinico-pathological and immuno-histochemical population-based study of 32 patients
    Åpne denne publikasjonen i ny fane eller vindu >>Patients suffering from both Hodgkin's disease and non-Hodgkin's lymphoma: a clinico-pathological and immuno-histochemical population-based study of 32 patients
    1997 (engelsk)Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 71, nr 4, s. 510-516Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) appearing in the same individual indicates a closer relationship between the 2 diseases than previously believed. The purpose of our study was to analyze cases of HD and NHL in a defined population clinically, histopathologically and immunohistochemically to look for similarities indicating a common cellular origin. Between 1974 and 1994, 77 individuals were identified from the Swedish Cancer Registry and the National Health Care Programme for HD as potentially having both diagnoses. Thirty-two patients who had both HD and NHL were available for histo-pathological re-examination and immunohistochemical staining with CD30, CD15, LMP, p53, CD45 (LCA), CD3, CD45R0 (UCHL-1), L26, MB2 and CD45R (4KB5). The most common relation was HD preceding a high-grade malignant NHL (16 of 32 patients), unexpectedly often of T-cell phenotype (7 of 16 patients). The next common association was NHL of B-CLL type followed by HD (7 of 32 patients). At clinical presentation, the first lymphoma did not differ from lymphomas not associated with a second lymphoma, whereas the second one often appeared with a disseminated and aggressive clinical form. There was a significant correlation between the expression of p53 and LMP in first and second lymphomas. CD3 antibody was frequently expressed both in HD and NHL, whereas positivity for B-cell-related antibodies, CD30, CD15 and CD45R0, was less frequent and generally lower than previously described. The occurrence of HD and NHL in an individual is unusual. Tumour biological features common to both HD and NHL may indicate a similar cellular origin, regardless of the time interval between the diagnoses, and may contribute to the understanding of the pathogenesis of lymphoma.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89775 (URN)10.1002/(SICI)1097-0215(19970516)71:4<510::AID-IJC2>3.0.CO;2-X (DOI)9178801 (PubMedID)
    Tilgjengelig fra: 2002-04-05 Laget: 2002-04-05 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    2. Treatment outcome in patients younger than 60 years with advanced stages (IIB-IV) of Hodgkin's disease: the Swedish National Health Care Programme experience
    Åpne denne publikasjonen i ny fane eller vindu >>Treatment outcome in patients younger than 60 years with advanced stages (IIB-IV) of Hodgkin's disease: the Swedish National Health Care Programme experience
    Vise andre…
    2000 (engelsk)Inngår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 65, nr 6, s. 379-389Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: Despite improved treatment results achieved in Hodgkin's disease (HD), only about 70% of patients with advanced stages are cured. The primary aim of this study was to evaluate the outcome of advanced stages (IIB-IVB) of HD in younger patients in an unselected population-based group of patients. The patients were recommended individualized treatment with respect to number of chemotherapy (CT) courses and post-CT radiotherapy (RT) based on pretreatment characteristics and tumour response. Secondly, we investigated if variables of prognostic importance could be detected.

    PATIENTS AND METHODS: Between 1985-92, 307 patients between 17-59 yr of age (median 36) were diagnosed with HD in stages IIB-IVB in 5/6 health care regions in Sweden. Median follow-up time was 7.8 yr (1.3-13). Retrospectively, laboratory parameters were collected.

    RESULTS: In total, 267 (87%) patients had a complete response (CR). The overall and disease-free 10-yr survivals in the whole cohort were 76% and 67%, respectively. There was no difference in survival between the groups of patients who received 6 or 8 cycles of CT. Survival was not higher for patients in CR after CT when RT was added. For those in PR after CT, additional RT raised the frequencies of CR. A selected group of pathologically staged patients was successfully treated with a short course (2 cycles) of CT + RT. In univariate analyses survival was affected by age, stage IVB, bone-marrow involvement, B-symptoms, S-LDH, S-Alb and reaching CR or not after 2, 4 and 6 cycles of CT. In a multivariate analysis, age and reaching CR after 6 cycles of CT remained statistically significant.

    CONCLUSIONS: The lack of difference in survival between the groups of patients who received 6 versus 8 cycles of CT indicates a successful selection of patients for the shorter treatment. Reaching a rapid CR significantly affected outcome. Whether some patients need less CT than the generally recommended 8 courses can properly only be evaluated in a randomised study. Additional RT may play a role in successful outcome, particularly if residual tumours are present, but its precise role can also only be defined in prospectively randomised studies. Reaching CR after CT was the most important variable affecting survival besides age.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89776 (URN)10.1034/j.1600-0609.2000.065006379.x (DOI)11168495 (PubMedID)
    Tilgjengelig fra: 2002-04-05 Laget: 2002-04-05 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    3. A population-based study of the outcome for patients with first relapse of Hodgkin lymphoma
    Åpne denne publikasjonen i ny fane eller vindu >>A population-based study of the outcome for patients with first relapse of Hodgkin lymphoma
    Vise andre…
    2002 (engelsk)Inngår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 68, nr 4, s. 225-232Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND:

    Our aims were to evaluate the response to salvage treatment in relation to initial treatment and to evaluate prognostic factors at the time of relapse in an unselected population of relapsing patients with Hodgkin's lymphoma (HL).

    PATIENTS AND METHODS:

    In total, 124 patients younger than 60 yr of age with initial diagnosis of HL in Sweden relapsed between 1985 and 1995.

    RESULTS:

    Fifty-eight patients relapsed after initial treatment with radiotherapy (RT) only, 62 after combination chemotherapy (CT), of whom 30 had received additional involved-field RT, and four after a short course of CT followed by extended-field RT. For 37 patients among the 58 relapsers after initial RT treated according to the recommendations of the National guidelines, the 5-yr Hodgkin-specific survival (HLS) was 85%, overall survival (OS) 73% and event-free survival (EFS) 62%, which is not inferior to survival in patients with primarily advanced stages. It was poorer in the 21 patients who initially had received RT only, even though they had been recommended for more extensive treatment. For patients initially treated with a full course (6-8 cycles) of CT the 5-yr HLS was 60%, OS 58% and EFS 22%. Bulky disease and age at diagnosis strongly affected survival in a multivariate analysis.

    CONCLUSIONS:

    Patients initially treated with RT who relapse have a favourable outcome, provided they have been treated according to the recommendations of the guidelines at the time of diagnosis. Initially bulky disease and, as a consequence, additional RT as part of the initial treatment negatively affect survival at relapse in patients initially treated with a full course of CT.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89777 (URN)10.1034/j.1600-0609.2002.01565.x (DOI)12071938 (PubMedID)
    Tilgjengelig fra: 2002-04-05 Laget: 2002-04-05 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    4. Relapsed Hodgkin's lymphoma: immunostaining patterns in relation to survival
    Åpne denne publikasjonen i ny fane eller vindu >>Relapsed Hodgkin's lymphoma: immunostaining patterns in relation to survival
    Vise andre…
    2002 (engelsk)Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 43, nr 6, s. 1253-1260Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Patients with relapsing Hodgkin's lymphoma (HL) have a rather poor prognosis and mechanisms that lead to resistance to therapy are poorly understood. Our aims were to investigate the immunohistochemical staining patterns of Rb (retinoblastoma protein) and the p53 tumour suppressor protein in HL at initial presentation and at relapse in order to elucidate a possible role in disease progression and resistance to therapy. Further to evaluate the presence and prognostic importance of Epstein-Barr virus (EBV) and anaplastic lymphoma kinase (ALK). Eighty-one cases of relapsing HL were reexamined histopathologically and immunostained for the expression of p53, Rb, ALK and CD30. EBV was detected with LMP-1 stainings and in situ hybridisation for EBER. Clinical data were extracted from the Swedish National Health Care Programme for HL. Median follow-up time was six years (range 0-12) from the date of relapse. The majority of cases were positive for p53 and Rb both at presentation and at relapse, though to a different extent. Both an increase and a decrease in the proportion of stained tumour cells were observed. None of our cases was ALK-positive and 44% were EBV-positive. No specific staining pattern was directly correlated to survival. In 12 patients a switch in HL subtype from diagnosis to relapse was observed and the five-year Hodgkin-specific survival (HLS) was statistically significantly inferior, 37 vs 81% (p = 0.002), in those patients. We found a significant relation between the expression of p53 and EBV at diagnosis and relapse, indicating a clonal relationship. We were unable to find any specific staining pattern of p53 or Rb, affecting survival.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89778 (URN)10.1080/10428190290026303 (DOI)12152993 (PubMedID)
    Tilgjengelig fra: 2002-04-05 Laget: 2002-04-05 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    5. A novel B-cell line (U-2932) established from a patient with a diffuse large B-cell lymphoma following Hodgkin lymphoma
    Åpne denne publikasjonen i ny fane eller vindu >>A novel B-cell line (U-2932) established from a patient with a diffuse large B-cell lymphoma following Hodgkin lymphoma
    Vise andre…
    2002 (engelsk)Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 43, nr 11, s. 2179-2189Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Little is known about mechanisms leading to secondary non-Hodgkin lymphomas (NHL) in patients treated for Hodgkin lymphoma (HL). Our aim was to characterise in detail a cell line derived from a diffuse large B-cell lymphoma (DLBCL) that had developed in a patient with relapsing HL. The cell line U-2932 was established from ascites in a patient suffering from DLBCL previously treated for HL with multiple chemotherapy regimens. Characterisation was based on morphology, immunophenotype, Epstein-Barr virus (EBV)-status, IgH gene rearrangement status, tumourigenicity, p53 sequencing, and immunohistochemical expression of p53, BCL-2 and BCL-6. The karyotype was investigated using G-banding, comparative genomic hybridisation (CGH) and spectral karyotype (SKY) analysis. This cell line shows typical morphological features of a DLBCL and grows as colonies in nude mice. It expresses a B-cell phenotype with a somatically hypermutated V(H)4-39 gene and is negative for EBV. The origin of U-2932 was confirmed by demonstrating an identical V(H)4 rearrangement in ascites from the patient. A point mutation of the tumour-suppressor gene p53 was detected in amino acid position 176 and immunohistochemical over-expression of the p53 protein was also demonstrated. U-2932 carries a complex karyotype including high-level amplifications of the chromosomal bands 18q21 and 3q27 and expresses aberrant BCL-2 and BCL-6 immunohistochemically. We were unable to investigate the clonal relationship between the original HL and U-2932. In conclusion, U-2932 is a unique B cell line established from a patient suffering from HL followed by NHL. Overexpression of BCL-2, BCL-6 and p53 may play a role in the tumourigenesis and drug resistance. This cell line may become a useful tool to better understand the mechanisms responsible for development of secondary NHL in patients treated for HL.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89779 (URN)10.1080/1042819021000032917 (DOI)12533045 (PubMedID)
    Tilgjengelig fra: 2002-04-05 Laget: 2002-04-05 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 29.
    Anderberg, Ulla Maria
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Fibromyalgia syndrome in women - a stress disorder?: Neurobiological and hormonal aspects1999Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The FMS is almost exclusively a female disorder, as 90% of the patients struck by it are women. About 7% of all women in modern society have this disorder.

    The studies in this thesis demonstrated that variations in the female sex hormones over the menstrual cycle and in different hormonal states are important with respect to the severity of pain and other symptoms, global functioning and well being of FMS patients. The hormonal state is also of importance in the inter-connection with the monoaminergic systems, stress systems and pain processing systems. Besides the symptoms, this also appears as perturbed levels of neuropeptide Y (NPY), nociceptin and oxytocin in plasma.

    The importance of estrogen to pain processing peptides was shown in an animal study. In that study it was revealed that estrogen increase reduces pain sensitivity, and that estrogen is also able to change the levels of pain processing peptides such as substance P (SP) and met-enkephalin-Arg-Phe (MEAP) in certain brain areas, spinal cord and serum. It is suggested that stress may elicit pain through several neuroendocrinological mechanisms.

    All FMS patients scored higher than healthy women on mood and tension related symptoms, which is interpreted as an increased sensitivity and reaction to stress. FMS patients at the time of menstruation, and older, postmenopausal FMS patients were the most sensitive to these changes.

    The increased sensitivity to stress was also demonstrated in a personality study using the Temperament and Character Inventory (TCI), which showed that many female FMS patients are more anxious and worried and therefore also become easily fatigued.

    It is likely that development of the FMS is due to numerous biological events occurring in response to long-term stress. Women with stressful life experiences and anxious personality traits are probably more prone to develop this disorder, although various and sufficient stressful events of different origins can most likely lead to this disorder in any woman over the long run.

  • 30.
    Andershed, Birgitta
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Att vara nära anhörig i livets slut: Delaktighet i ljuset - delaktighet i mörkret1998Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The aims of the present dissertation were: 1. To describe how the establishment of an inpatient hospice ward affected dying cancer patients' utilisation of care at a Medical Centre Hospital; 2. To analyse the involvement of the relative in the care of gravely ill cancer patients in different care cultures; 3. To analyse obstacles to and possibilities for relatives' involvement: 4. To develop a theoretical framework of understanding concerning the involvement of relatives. For the first aim, data was collected via register studies. The basic research design for the other aims was the hermeneutic method.

    The results show that during the first three years 315 patients died at the newly opened hospice ward. The year before the ward opened 82% of the cancer patients died in acute care compared with 59% during the third year of the hospice ward.

    The involvement of relatives in the patients' care was categorised into three main categories: "to know", " to be" and "to do". The studies show that the involvement can be described either as involvement in the light or involvement in the dark. Involvement in the light and in the dark illustrates relatives' understanding of the situation, their possibilities for involvement, and the attitude of the staff toward the relatives. Factors that promoted involvement in the light were a humanistic attitude of the staff, a stronger sense of coherence of relatives, an appropriate course of illness, and other available resources such as other relatives and one's own health.

    A surprising result was that the time between diagnosis and death was three months or less for 49% of 67 patients. In those cases where the course of illness was short there was no time to lose, and it was important that caring delays were avoided.

    The results from the substudies were summarised in five statements, which together form a theoretical framework of understanding for the involvement of relatives.

  • 31.
    Andersson, Agneta
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Fatty Acid Composition in Skeletal Muscle: Influence of Physical Activity and Dietary Fat Quality2001Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Insulin sensitivity is related to the fatty acid profile of skeletal muscle. The aim of this thesis was to investigate whether physical activity and dietary fat quality, independent of each other, influence the fatty acid composition of the skeletal muscle lipids. In an intervention study where middle-aged men were exercising for six weeks, and in a cross-sectional study comparing sedentary with endurance trained young men, it was demonstrated that the fatty acid composition of skeletal muscle lipids differed between physical active and inactive men. In brief, a lower proportion of palmitic acid (16:0) and total n-6 polyunsaturated fatty acids (PUFA) and a higher proportion of stearic (18:0) and oleic acid (18:1n-9) and total n-3 PUFA in the muscle phospholipids were associated with physical activity, despite similar fatty acid composition of the diet. In the second study, that included a larger training volume, differences in the fatty acid profile were also found in the skeletal muscle triglycerides.

    In contrast, after short-term supra-maximal exercise we found no significant changes in the proportion of the fatty acids in skeletal muscle.

    Furthermore, after a treatment period of three months, with diets with various dietary fat quality, the proportions of saturated fatty acids (14:0, 15:0 and 17:0) were higher and the proportion of 18:1 n-9 lower in subjects with a high intake of saturated fatty acids compared with subjects with a high intake of monounsaturated fatty acids. In addition subjects given n-3 supplementation had a higher proportion of total n-3 PUFA and lower n-6 PUFA in the skeletal muscle phospholipids than controls. Differences similar to those observed in the phospholipids were found in the triglycerides.

    In summary, these results suggest that regular aerobic physical activity and dietary fat quality influence the fatty acid composition of the skeletal muscle lipids, which may affect insulin sensitivity and glucose homeostasis.

    Delarbeid
    1. Effects of physical exercise on phospholipid fatty acid composition in skeletal muscle
    Åpne denne publikasjonen i ny fane eller vindu >>Effects of physical exercise on phospholipid fatty acid composition in skeletal muscle
    1998 (engelsk)Inngår i: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 274, nr 37, s. E432-E438Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The effects of low-intensity exercise on the fatty acid composition in skeletal muscle and in serum were studied in 19 sedentary, middle-aged Swedish men. During a 10-wk period, all subjects were given a standardized diet with an identical fat composition. After 4 wk on this diet, they were randomly allocated to a daily exercise program (55% peak oxygen uptake) or to continue to live a sedentary life for the remaining 6 wk. Aerobic capacity (submaximal bicycle test) and peripheral insulin sensitivity (hyperinsulinemic euglycemic clamp) improved with training, whereas the body weight as well as the body composition (underwater weighing and bioimpedance) were unchanged. The proportions of palmitic acid (16:0) and linoleic acid [18:2(n-6)] and the sum of n-6 fatty acids [18:2(n-6), 20:3(n-6), 20:4(n-6)] were decreased in skeletal muscle phospholipids, whereas the proportion of oleic acid [18:1(n-9)] was increased, by training. The fatty acid profile in skeletal muscle triglycerides remained unchanged. We conclude that regular low-intensity exercise influences the fatty acid composition of the phospholipids in skeletal muscle, which hypothetically may contribute to changes of the skeletal muscle membrane fluidity and influence the peripheral insulin sensitivity.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89436 (URN)9530125 (PubMedID)
    Tilgjengelig fra: 2001-09-19 Laget: 2001-09-19 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    2. Fatty acid profile of skeletal muscle phospholipids in trained and untrained young men
    Åpne denne publikasjonen i ny fane eller vindu >>Fatty acid profile of skeletal muscle phospholipids in trained and untrained young men
    Vise andre…
    2000 (engelsk)Inngår i: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 279, nr 4, s. E744-E751Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Endurance trained (n = 14) and untrained young men (n = 15) were compared regarding the fatty acid profile of the vastus lateralis muscle after 8 wk on diets with a similar fatty acid composition. The skeletal muscle phospholipids in the trained group contained lower proportions of palmitic acid (16:0) (-12.4%, P < 0.001) and di-homo-gamma-linolenic acid [20:3(n-6)] (-15.3%, P = 0.018), a lower n-6-to-n-3 ratio (-42.0%, P = 0.015), higher proportions of stearic acid (18:0) (+9.8%, P = 0.004) and sum of n-3 polyunsaturated fatty acids (+33.8%, P = 0.009), and a higher ratio between 20:4(n-6) to 20:3(n-6) (+18.4%, P = 0.006) compared with those in the untrained group. The group differences in 16:0, 20:3(n-6), 18:0/16:0, and 20:4(n-6)/20:3(n-6) were independent of fiber-type distribution. The trained group also showed a lower proportion of 16:0 (-7.9%, P < 0.001) in skeletal muscle triglycerides irrespective of fiber type. In conclusion, the fatty acid profile of the skeletal muscle differed between trained and untrained individuals, although the dietary fatty acid composition was similar. This difference was not explained by different fiber-type distribution alone but appears to be a direct consequence of changes in fatty acid metabolism due to the higher level of physical activity.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89437 (URN)11001754 (PubMedID)
    Tilgjengelig fra: 2001-09-19 Laget: 2001-09-19 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    3. Unchanged proportion of polyunsaturated fatty acids in skeletal muscle phospholipids after supra-maximal exercise
    Åpne denne publikasjonen i ny fane eller vindu >>Unchanged proportion of polyunsaturated fatty acids in skeletal muscle phospholipids after supra-maximal exercise
    Vise andre…
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-89438 (URN)
    Tilgjengelig fra: 2001-09-19 Laget: 2001-09-19 Sist oppdatert: 2010-01-13bibliografisk kontrollert
    4. Fatty acid composition of skeletal muscle reflects dietary fat compositionin humans
    Åpne denne publikasjonen i ny fane eller vindu >>Fatty acid composition of skeletal muscle reflects dietary fat compositionin humans
    2002 (engelsk)Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 76, nr 6, s. 1222-1229Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: It is still unknown whether the fatty acid composition of human skeletal muscle lipids is directly influenced by the fat composition of the diet.

    Objective: We investigated whether the fatty acid composition of the diet is reflected in the fatty acid profile of skeletal muscle phospholipids and triacylglycerols.

    Design: Thirty-two healthy adults (25 men and 7 women) included in a larger controlled, multicenter dietary study were randomly assigned to diets containing a high proportion of either saturated fatty acids (SFAs) [total fat, 36% of energy; SFAs, 18% of energy; monounsaturated fatty acids (MUFAs), 10% of energy] or MUFAs (total fat, 35% of energy; SFAs, 9% of energy; MUFAs, 19% of energy) for 3 mo. Within each diet group, there was a second random assignment to supplementation with fish oil capsules [containing 3.6 g n−3 fatty acids/d; 2.4 g eicosapentaenoic acid (20:5n−3) and docosahexaenoic acid (22:6n−3)] or placebo. A muscle biopsy sample was taken from the vastus lateralis muscle after the diet period. Parallel analyses of diet and supplementation effects were performed.

    Results: The proportions of myristic (14:0), pentadecanoic (15:0), heptadecanoic (17:0), and palmitoleic (16:1n−7) acids in the skeletal muscle phospholipids were higher and the proportion of oleic acid (18:1n−9) was lower in the SFA group than in the MUFA group. The proportion of total n−3 fatty acids in the muscle phospholipids was ≈2.5 times higher, with a 5 times higher proportion of eicosapentaenoic acid (20:5n−3), in subjects supplemented with n−3 fatty acids than in those given placebo. Similar differences were observed in the skeletal muscle triacylglycerols.

    Conclusion: The fatty acid composition of skeletal muscle lipids reflects the fatty acid composition of the diet in healthy men and women.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89439 (URN)
    Tilgjengelig fra: 2001-09-19 Laget: 2001-09-19 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 32.
    Andersson, Ann-Catrin
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Studies on Human Endogenous Retroviruses (HERVs) with Special Focus on ERV32002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Human endogenous retroviruses (HERVs) represent approximately 7% of the human genome. This investigation was focused on one particular HERV, ERV3, with the main purpose of characterising its gene expression patterns and genomic distribution of ERV3-like sequences. Furthermore, this careful expression study should provide insights into the biological role of HERVs. The impact of HERVs in health and disease is not yet clarified. ERV3 is expressed as three envelope (env) transcripts, of which two also contain a cellular gene, H-plk (human proviral linked Krüppel). ERV3 env expression was mainly investigated at the RNA level. The gene expression of two other HERVs, HERV-K and HERV-E was analysed and compared with ERV3 activity.

    Real-time PCRs were developed and in combination with in situ hybridisation, it was found that ERV3 is expressed in a tissue- and cell-specific way. High levels of ERV3 mRNA (up to six times over Histone3.3) were demonstrated in placenta, sebaceous glands, foetal and adult adrenal glands, brown adipose tissue, corpus luteum, pituitary gland, thymus and testis. In monocytic cells including both normal monocytes and malignant U-937 cells, elevated mRNA levels were observed after retinoic acid (RA)-induced differentiation. ERV3-encoded Env protein was detected in selected cases, one following RA-treatment. In addition, several new ERV3-like sequences were discovered in the human genome.

    ERV3 was found to have conserved open reading frames in contrast to other ERV3-like sequences in the human genome. This suggests that ERV3 may be involved in important cellular processes such as differentiation, cell fusion, immunomodulation and protection against infectious retroviruses. The developed techniques and obtained results will allow further studies of HERV expression to better correlate HERV activity to both normal development and disease.

    Delarbeid
    1. Elevated levels of the human endogenous retrovirus ERV3 in human sebaceous glands
    Åpne denne publikasjonen i ny fane eller vindu >>Elevated levels of the human endogenous retrovirus ERV3 in human sebaceous glands
    Vise andre…
    1996 (engelsk)Inngår i: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 106, nr 1, s. 125-128Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. Long terminal repeat-envelope (env) gene spliced mRNAs of 9 and 3.5 kb are widely expressed in human tissues and cells, but gag-pol mRNAs have not been found. Furthermore, the env gp70 gene contains an open reading frame throughout its length. The highest expression of ERV3 mRNA detected so far is in placenta and the lowest in choriocarcinoma cell lines. We have previously shown that the human monoblastic cell line U-937 and some normal and neoplastic tissues also express high levels of ERV3 env message by Northern blot analysis; however, this method does not distinguish between mRNA expression in different cell types in tissues. In this report, we have studied the ERV3 mRNA expression in specific cell types of human skin by in situ hybridization. We found high levels expression of ERV3 env mRNA in human sebaceous glands in normal skin and dermoid cysts of the ovary. In all glands, the expression is maximal in the periphery of the lobule and ceases towards the center in the region of characteristic holocrine secretion. Since it is known that the regulation of sebaceous glands is primarily via steroid hormones, particularly androgens, it is possible that expression of ERV3 is hormone dependent.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89897 (URN)10.1111/1523-1747.ep12329612 (DOI)8592062 (PubMedID)
    Tilgjengelig fra: 2002-05-10 Laget: 2002-05-10 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    2. Expression of the endogenous retrovirus ERV3 (HERV-R) during induced monocytic differentiation in the U-937 cell line
    Åpne denne publikasjonen i ny fane eller vindu >>Expression of the endogenous retrovirus ERV3 (HERV-R) during induced monocytic differentiation in the U-937 cell line
    Vise andre…
    1996 (engelsk)Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 67, nr 3, s. 451-456Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. LTR-env-gene-spliced mRNA of 9 and 3.5 Kb is widely expressed in human tissues and cells, but gag-pol mRNA has not been found. Further, the env gp70 gene contains an open reading frame throughout its length and its expression has recently been detected as a full-length protein. The highest expression of ERV3 detected so far is in placenta and the lowest in cytotrophoblasts and choriocarcinoma cell lines. In this report we have studied ERV3 mRNA and protein expression in the human monoblastic cell line U-937 during differentiation into monocytes/macrophages. Differentiation of U-937 cells was induced by 1,25a-dihydroxyvitamin D3 (vitD3), retinoic acid (RA), gamma interferon (IFN-gamma) and phorbol-myristate-acetate (PMA-TPA). The expression of ERV3 env mRNA was found to be differentiation-associated, with high expression detected in the late stages of monocytic development. Using TPA, the expression of ERV3 env was detected as 9- and 3.5-kb transcripts by Northern blotting, as mRNA by in situ hybridization and as a cytoplasmic 65-kDa protein by immunofluorescence and Western blots. Low levels of basal expression were found, with up-regulation of both message and protein at 24 to 48 hr after addition of TPA. Induction with vitD3, IFN-gamma and RA produced higher levels of mRNA at earlier time points. It is concluded that the U-937 cell line represents an excellent model system for further studies to study the relationship between ERV3 expression and cellular differentiation.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89898 (URN)10.1002/(SICI)1097-0215(19960729)67:3<451::AID-IJC23>3.0.CO;2-9 (DOI)8707424 (PubMedID)
    Tilgjengelig fra: 2002-05-10 Laget: 2002-05-10 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    3. Developmnental expression of HERV-R (ERV3) and HERV-K in human tissue
    Åpne denne publikasjonen i ny fane eller vindu >>Developmnental expression of HERV-R (ERV3) and HERV-K in human tissue
    Vise andre…
    2002 (engelsk)Inngår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 297, nr 2, s. 220-225Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The human endogenous retroviruses (HERVs), ERV3 (HERV-R) and HERV-K, are both known to be transcriptionally active in human placenta. In the case of ERV3 there is also indirect evidence for its participation in cellular differentiation. In this study we examined the expression of ERV3 (HERV-R) and HERV-K in human normal fetal tissues by in situ hybridization. The highest level of ERV3 env expression was detected in primitive adrenal cortex. Elevated levels of expression were also found in the following developing tissues: kidneys (tubules), tongue, heart, liver, and central nervous system. Tissue-specific expression was found for HERV-K rec (former cORF) but not for pol/int transcripts. The highest rec expression was found in placenta and levels slightly higher than sense control were found in the rest of the tissues examined. Pol/Int was not possible to quantitate. It appears that ERV3 is expressed in an organ-specific way during embryogenesis and might suggest a possible role in the development and differentiation of human tissues.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89899 (URN)10.1006/viro.2002.1428 (DOI)12083821 (PubMedID)
    Tilgjengelig fra: 2002-05-10 Laget: 2002-05-10 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    4. ERV3 and related sequences in humans; studies of RNA expression by real-time PCR and in situ hybridisation
    Åpne denne publikasjonen i ny fane eller vindu >>ERV3 and related sequences in humans; studies of RNA expression by real-time PCR and in situ hybridisation
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-89900 (URN)
    Tilgjengelig fra: 2002-05-10 Laget: 2002-05-10 Sist oppdatert: 2010-01-13bibliografisk kontrollert
    5. ERV3 in relation to cell differentiation in normal and neoplastic monocytes
    Åpne denne publikasjonen i ny fane eller vindu >>ERV3 in relation to cell differentiation in normal and neoplastic monocytes
    Vise andre…
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-89901 (URN)
    Tilgjengelig fra: 2002-05-10 Laget: 2002-05-10 Sist oppdatert: 2010-01-13bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 33.
    Andersson, Annika K.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Role of Inducible Nitric Oxide Synthase and Melatonin in Regulation of β-cell Sensitivity to Cytokines2003Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The mechanisms of β-cell destruction leading to type 1 diabetes are complex and not yet fully understood, but infiltration of the islets of Langerhans by autoreactive immune cells is believed to be important. Activated macrophages and T-cells may then secrete cytokines and free radicals, which could selectively damage the β-cells. Among the cytokines, IL-1β, IFN-γ and TNF-α can induce expression of inducible nitric synthase (iNOS) and cyclooxygenase-2. Subsequent nitric oxide (NO) and prostaglandin E2 (PGE2) formation may impair islet function.

    In the present study, the ability of melatonin (an antioxidative and immunoregulatory hormone) to protect against β-cell damage induced by streptozotocin (STZ; a diabetogenic and free radical generating substance) or IL-1β exposure was examined. In vitro, melatonin counteracted STZ- but not IL-1β-induced islet suppression, indicating that the protective effect of melatonin is related to interference with free radical generation and DNA damage, rather than NO synthesis. In vivo, non-immune mediated diabetes induced by a single dose of STZ was prevented by melatonin.

    Furthermore, the effects of proinflammatory cytokines were examined in islets obtained from mice with a targeted deletion of the iNOS gene (iNOS -/- mice) and wild-type controls. The in vitro data obtained show that exposure to IL-1β or (IL-1β + IFN-γ) induce disturbances in the insulin secretory pathway, which were independent of NO or PGE2 production and cell death. Initially after addition, in particular IL-1β seems to be stimulatory for the insulin secretory machinery of iNOS –/- islets, whereas IL-1β acts inhibitory after a prolonged period. Separate experiments suggest that the stimulatory effect of IL-1β involves an increased gene expression of phospholipase D1a/b. In addition, the formation of new insulin molecules appears to be affected, since IL-1β and (IL-1β + IFN-γ) suppressed mRNA expression of both insulin convertase enzymes and insulin itself.

    Delarbeid
    1. Melatonin protects against streptozotocin, but not Interleukin-1β-induced damage of rodent pancreatic β-cells
    Åpne denne publikasjonen i ny fane eller vindu >>Melatonin protects against streptozotocin, but not Interleukin-1β-induced damage of rodent pancreatic β-cells
    2001 Inngår i: J. Pineal Res., ISSN 0742-3098, Vol. 30, nr 3, s. 157-165Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-90711 (URN)
    Tilgjengelig fra: 2003-09-03 Laget: 2003-09-03bibliografisk kontrollert
    2. Cytokine-induced inhibition of insulin release from mouse pancreatic β-cells deficient in inducible nitric oxide synthase
    Åpne denne publikasjonen i ny fane eller vindu >>Cytokine-induced inhibition of insulin release from mouse pancreatic β-cells deficient in inducible nitric oxide synthase
    2001 Inngår i: Biochem. Biophys. Res. Commun., ISSN 0006-291, Vol. 281, nr 2, s. 396-403Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-90712 (URN)
    Tilgjengelig fra: 2003-09-03 Laget: 2003-09-03bibliografisk kontrollert
    3. Cytokine-induced prostaglandin E2 formation is reduced from mouse pancreatic islets deficient in inducible nitric oxide synthase
    Åpne denne publikasjonen i ny fane eller vindu >>Cytokine-induced prostaglandin E2 formation is reduced from mouse pancreatic islets deficient in inducible nitric oxide synthase
    (engelsk)Manuskript (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-90713 (URN)
    Tilgjengelig fra: 2003-09-03 Laget: 2003-09-03 Sist oppdatert: 2018-01-13
    4. Role of phospholipase D, insulin and proinsulin convertase gene expression in altered insulin secretion from β-cells deficient in inducible nitric oxide synthase following IL-1β and IFN-γ exposure
    Åpne denne publikasjonen i ny fane eller vindu >>Role of phospholipase D, insulin and proinsulin convertase gene expression in altered insulin secretion from β-cells deficient in inducible nitric oxide synthase following IL-1β and IFN-γ exposure
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-90714 (URN)
    Tilgjengelig fra: 2003-09-03 Laget: 2003-09-03 Sist oppdatert: 2010-01-13bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 34.
    Andersson, Charlotte
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Towards Pharmacological Treatment of Cystic Fibrosis2002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    S-nitrosogluthatione is an endogenous substance, present at decreased levels in the lungs of CF patients and was recently found to induce mature CFTR in airway epithelial CF cell lines. We show that S-nitrosoglutathione in physiological concentrations increases the presence of ΔF508 CFTR in the cell membrane and induces cAMP dependent chloride transport in cystic fibrosis airway epithelial cells. The properties of S-nitrosoglutathione include other potential benefits for the CF patient and make this agent an interesting candidate for pharmacological treatment of CF that needs to be further evaluated.

    Genistein was found to increase the chloride efflux in both normal and ΔF508 cells without stimulation of cAMP elevating agents and without prior treatment with phenylbutyrate. Genistein, in concentrations close to those that can be detected in plasma after a high soy diet, could induce chloride efflux in cells with the ΔF508 CFTR mutation and its possible use in the treatment of CF should therefore be further investigated.

    Studies on nasal epithelial cells from CF patients showed cAMP dependent chloride efflux in some of the patients with severe genotypes. This may complicate in vitro evaluation of clinical treatment of these patients. The presence of cAMP dependent chloride transport did not necessarily lead to a milder phenotype. Other factors than CFTR may influence the clinical development of the disease.

    Cystic fibrosis (CF) is the most common monogenetic disease among Caucasians. A defective cAMP regulated chloride channel (cystic fibrosis transmembrane conductance regulator, CFTR) in epithelial cells leads to viscous mucus, bacterial infections, inflammation and tissue damage in the lungs that cause death in 95% of the cystic fibrosis patients. There is no cure for the disease although existing treatment has dramatically prolonged the life expectancy. The aim of this thesis was to study pharmacological agents for their ability to restore the cellular deficiency in CF airway epithelial cells. X-ray microanalysis, MQAE fluorescence and immunocytochemistry were used to evaluate the effects.

    Delarbeid
    1. Activation of deltaF508 CFTR in a cystic fibrosis respiratory epithelial cell line by 4-phenylbutyrate, genistein and CPX
    Åpne denne publikasjonen i ny fane eller vindu >>Activation of deltaF508 CFTR in a cystic fibrosis respiratory epithelial cell line by 4-phenylbutyrate, genistein and CPX
    2000 Inngår i: Eur Respir J., Vol. 15, nr 5, s. 937-41Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-89966 (URN)
    Tilgjengelig fra: 2002-10-11 Laget: 2002-10-11bibliografisk kontrollert
    2. Activation of CFTR by genistein in human airway epithelial cell lines
    Åpne denne publikasjonen i ny fane eller vindu >>Activation of CFTR by genistein in human airway epithelial cell lines
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-89967 (URN)
    Tilgjengelig fra: 2002-10-11 Laget: 2002-10-11 Sist oppdatert: 2010-01-13bibliografisk kontrollert
    3. S-Nitrosoglutathione induces functional ?F508-CFTR in airway epithelial cells
    Åpne denne publikasjonen i ny fane eller vindu >>S-Nitrosoglutathione induces functional ?F508-CFTR in airway epithelial cells
    2002 Inngår i: Biochem Biophys Res Commun., Vol. 297, s. 552-557Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-89968 (URN)
    Tilgjengelig fra: 2002-10-11 Laget: 2002-10-11bibliografisk kontrollert
    4. Determination of chloride efflux by X-ray microanalysis versus MQAE-fluorescence
    Åpne denne publikasjonen i ny fane eller vindu >>Determination of chloride efflux by X-ray microanalysis versus MQAE-fluorescence
    2002 (engelsk)Inngår i: Microscopy research and technique (Print), ISSN 1059-910X, E-ISSN 1097-0029, Vol. 59, nr 6, s. 531-355Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The importance of chloride channels for the cell is demonstrated by a number of serious human diseases that are due to mutations in chloride channels. The most well-known of these diseases is cystic fibrosis. Investigations into the mechanisms of the disease and possible treatments require the study of chloride fluxes at the level of individual cells. The present study compares two methods for studies of chloride transport: X-ray microanalysis and MQAE fluorescence with image analysis. As an experimental system, the cAMP-activated chloride channel in cultured respiratory epithelial cells was chosen. Both methods showed that stimulation with the cAMP-elevating agents forskolin and IBMX decreased the chloride content of the cells by about 20-27%. Inducing a driving force for chloride by replacing extracellular chloride by nitrate resulted in a chloride efflux that was significantly increased in the presence of forskolin and IBMX. This study shows that X-ray microanalysis and MQAE fluorescence are adequate and comparable methods for measuring cAMP-dependent chloride transport in individual cells.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-89969 (URN)10.1002/jemt.10234 (DOI)12467030 (PubMedID)
    Tilgjengelig fra: 2002-10-11 Laget: 2002-10-11 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    5. Assessment of chloride secretion in human nasal epithelial cells by X-ray microanalysis
    Åpne denne publikasjonen i ny fane eller vindu >>Assessment of chloride secretion in human nasal epithelial cells by X-ray microanalysis
    2001 Inngår i: J Microsc., Vol. 203, nr 3, s. 277-84Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-89970 (URN)
    Tilgjengelig fra: 2002-10-11 Laget: 2002-10-11bibliografisk kontrollert
    6. CFTR) activity in nasal epithelial cells from cystic fibrosis patients with severe genotypes
    Åpne denne publikasjonen i ny fane eller vindu >>CFTR) activity in nasal epithelial cells from cystic fibrosis patients with severe genotypes
    2002 Inngår i: Clin Sci., Vol. 103, s. 417-424Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-89971 (URN)
    Tilgjengelig fra: 2002-10-11 Laget: 2002-10-11bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 35.
    Andersson, Dan K. G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Diabetes mellitus in a defined population: a longitudinal study with special reference to early diagnosis, occurrence and mortality1994Doktoravhandling, med artikler (Annet vitenskapelig)
  • 36.
    Andersson, Gerhard
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Clinical Aspects of Tinnitus- Course, Cognition, PET, and the Internet2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The purpose of this thesis was to develop novel ways to study tinnitus, to investigate the course of tinnitus, and to study the effects of cognitive-behaviour therapy on tinnitus related distress. Data from 377 tinnitus patients were collected.

    A group of 216 patients completed audiological measures and were assessed in a structured interview. The Klockhoff and Lindblom's grading system was used and its inter-rater reliability assessed in a subsample showing a high degree of correspondence. A discriminant analysis showed that a substantial proportion of patients could be correctly classified into grade II or III, by measures of pitch, minimal masking level of tinnitus, avoidance of situations because of tinnitus, and tolerance in relation to onset.

    Using tests developed in cognitive psychology, it was found that tinnitus patients had impaired performance. There was no evidence for an attentional bias towards tinnitus related words using a computerized emotional Stroop task, but masking sounds of an "on-and-off" character were more disruptive than constant masking when patients performed the digit-symbol test. It is suggested that tinnitus distress may be increased by the 'changing-state' character of the tinnitus signal, or alternatively by intermittent masking sounds.

    In a case-study a patient received an i.v. injection of lidocaine while Positron Emission Tomograpy was conducted. The brain activity associated with tinnitus included the left primary, secondary and integrative auditory brain areas, as well as right paralimbic areas related to negative feelings. The precuneus (Brodmann area 7) might be a brain area involved in the aversiveness associated with tinnitus.

    Using a tinnitus questionnaire as the dependent measure it was found that tinnitus maskability at admission predicted distress at follow-up for an average of five years following admission. Some improvement in tinnitus occurred over time, but this was more evident in patients who had received a cognitive-behavioural treatment program.

    The effect of an Internet based cognitive-behavioural self-help treatment program for tinnitus was investigated showing a high dropout rate, but with positive results in that the treated patients improved.

    Fulltekst (pdf)
    FULLTEXT01
  • 37.
    Andersson, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Concerted evolution of human class II major histocompatibility genes1987Doktoravhandling, med artikler (Annet vitenskapelig)
  • 38.
    Andersson, Jesper
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Functional neuroimaging with PET: methodological aspects1995Doktoravhandling, med artikler (Annet vitenskapelig)
  • 39.
    Andersson, Jonas
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Complement Activation Triggered by Biomaterial Surfaces: Mechanisms and Regulation2003Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Today there are a vast number of medical devices in temporary or permanent contact with human tissues. Blood-biomaterial contact is known to trigger the complement system and results in generation of fluid phase anaphylatoxins C3a and C5a, and surface-bound C3b and iC3b. All these products together are able to attract and activate leukocytes and trigger release of inflammatory mediators leading to a systemic inflammation indirectly causing hemostatic problems and even organ failure. The aim of this study was to identify how complement is triggered on a biomaterial surface and to find ways to regulate this activation.

    The finding that complement activation on biomaterials can be divided into initiation and amplification will facilitate regulation of complement activation biomaterial surfaces. This concept is also compatible with the two techniques to regulate complement activation on a surface.

    Delarbeid
    1. Complement activation on a model biomaterial surface: Binding of C3b via the alternative pathway amplification loop to plasma proteins adsorbed to the surface
    Åpne denne publikasjonen i ny fane eller vindu >>Complement activation on a model biomaterial surface: Binding of C3b via the alternative pathway amplification loop to plasma proteins adsorbed to the surface
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-90375 (URN)
    Tilgjengelig fra: 2003-04-24 Laget: 2003-04-24 Sist oppdatert: 2010-01-13bibliografisk kontrollert
    2. C3 Adsorbed to a Polymer Surface Can Form an Initiating Alternative Pathway Convertase
    Åpne denne publikasjonen i ny fane eller vindu >>C3 Adsorbed to a Polymer Surface Can Form an Initiating Alternative Pathway Convertase
    Vise andre…
    2002 Inngår i: Journal of Immunology, ISSN 0022-1767, Vol. 168, nr 11, s. 5786-5791Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-90376 (URN)
    Tilgjengelig fra: 2003-04-24 Laget: 2003-04-24bibliografisk kontrollert
    3. Binding of a model regulator of complement activation (RCA) to a biomaterial surface: surface-bound factor H inhibits complement activation
    Åpne denne publikasjonen i ny fane eller vindu >>Binding of a model regulator of complement activation (RCA) to a biomaterial surface: surface-bound factor H inhibits complement activation
    Vise andre…
    2001 Inngår i: Biomaterials, ISSN 0142-9612, Vol. 22, nr 17, s. 2435-2443Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-90377 (URN)
    Tilgjengelig fra: 2003-04-24 Laget: 2003-04-24bibliografisk kontrollert
    4. Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro
    Åpne denne publikasjonen i ny fane eller vindu >>Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro
    Vise andre…
    2003 (engelsk)Inngår i: Journal of Biomedical Materials Research, ISSN 0021-9304, E-ISSN 1097-4636, Vol. 67, nr 2, s. 458-466Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Contact between blood and a biomaterial surface takes place in many applications and is known to activate the coagulation and complement systems. Heparin surface coatings have been shown to reduce blood activation upon contact with artificial surfaces. To establish the optimal heparin surface concentration, blood was incubated in a tubing loop model at 37 degrees C. The tubing was coated with different surface concentrations of heparin and rotated at three different velocities. We demonstrate that the blood compatibility of a surface with regard to coagulation, complement, and platelet activation can be improved by increasing the heparin surface concentration in the 6-12 pmol antithrombin/cm2 concentration interval. The binding of factor H is not influenced by the increased heparin surface concentration, suggesting that this factor is not the primary regulator of complement on heparin surfaces. In addition, the heparin coating has no effect on the complement activation that occurs on gas surfaces in extracorporeal circuits.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-90378 (URN)10.1002/jbm.a.10104 (DOI)14566786 (PubMedID)
    Tilgjengelig fra: 2003-04-24 Laget: 2003-04-24 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 40.
    Andersson, Karl
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Characterization of Biomolecular Interactions Using a Multivariate Approach2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis presents a novel bioinformatic methodology denoted the bio-chemometric approach. The methodology is designed for generation of detailed descriptions and predictions of biomolecular interactions. It is based on multivariate analysis of the sensitivity of a biomolecular interaction to multiple minor changes in the experimental conditions. In this work, either the chemical environment where the interaction takes place, or the molecular structure of one of the interacting molecules, was varied. The sensitivity of the interaction to the performed variations was presented as a vector called the sensitivity fingerprint. The bio-chemometric approach was tested on several biomolecular interactions. Useful descriptions of the interactions were obtained by measuring binding kinetics for each interaction in 12-20 different buffers and correlating buffer composition to binding kinetics. The obtained chemical sensitivity fingerprints were reproducible, significantly different and showed a weak correlation to binding site properties for the tested interactions. The results indicate that the fingerprints contained useful information about the binding site. The predictive ability of the bio-chemometric approach was tested on two different biomolecular interactions where one of the binding partners was slightly modified into multiple analogues by amino acid exchanges. In one example, interactions of 18 peptide analogues with an antibody gave data that could be used for accurate prediction of the dissociation rates of novel analogues. Reliable predictions of binding kinetics and affinity were also obtained for single domain camel antibody analogues binding to a protein antigen. By using the three-dimensional structure of camel antibodies and data obtained using the bio-chemometric approach, even the importance of non-exchanged amino acids for the binding could be estimated. The bio-chemometric approach can potentially improve the development of peptides and proteins for therapeutic and diagnostic use. It is suggested to be valid for general use in biochemistry.

    Delarbeid
    1. Identification and Optimization of Regeneration Conditions for Affinity-Based Biosensor Assays. A Multivariate Cocktail Approach
    Åpne denne publikasjonen i ny fane eller vindu >>Identification and Optimization of Regeneration Conditions for Affinity-Based Biosensor Assays. A Multivariate Cocktail Approach
    1999 Inngår i: Analytical Chemistry, Vol. 71, s. 2475-2481Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91945 (URN)
    Tilgjengelig fra: 2004-06-02 Laget: 2004-06-02bibliografisk kontrollert
    2. Kinetic Characterization of the Interaction of the Z-fragment of Protein A With Mouse-IgG3 in a Volume in Chemical Space
    Åpne denne publikasjonen i ny fane eller vindu >>Kinetic Characterization of the Interaction of the Z-fragment of Protein A With Mouse-IgG3 in a Volume in Chemical Space
    Vise andre…
    1999 Inngår i: Proteins: Structure, Function, and Genetics, Vol. 37, s. 494-498Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91946 (URN)
    Tilgjengelig fra: 2004-06-02 Laget: 2004-06-02bibliografisk kontrollert
    3. Predicting the kinetics of peptide-antibody interactions using a multivariate experimental design of sequence and chemical space
    Åpne denne publikasjonen i ny fane eller vindu >>Predicting the kinetics of peptide-antibody interactions using a multivariate experimental design of sequence and chemical space
    Vise andre…
    2001 (engelsk)Inngår i: Journal of Molecular Recognition, Vol. 14, s. 62-71Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91947 (URN)
    Tilgjengelig fra: 2004-06-02 Laget: 2004-06-02 Sist oppdatert: 2010-09-14bibliografisk kontrollert
    4. Kinetic and affinity predictions of a protein-protein interaction using multivariate experimental design
    Åpne denne publikasjonen i ny fane eller vindu >>Kinetic and affinity predictions of a protein-protein interaction using multivariate experimental design
    Vise andre…
    2002 Inngår i: Journal of Biological Chemistry, Vol. 277, nr 33, s. 29897-29907Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91948 (URN)
    Tilgjengelig fra: 2004-06-02 Laget: 2004-06-02bibliografisk kontrollert
    5. Structural Modeling Extends QSAR Analysis of Antibody-Lysozyme Interactions to 3D-QSAR
    Åpne denne publikasjonen i ny fane eller vindu >>Structural Modeling Extends QSAR Analysis of Antibody-Lysozyme Interactions to 3D-QSAR
    2003 Inngår i: Biophysical Journal, Vol. 84, s. 2264-2272Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-91949 (URN)
    Tilgjengelig fra: 2004-06-02 Laget: 2004-06-02bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 41.
    Andersson, Lars-Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Renal function in hypothermic cardiac surgery: a clinical study with special reference to perfusion and metabolism1994Doktoravhandling, med artikler (Annet vitenskapelig)
  • 42.
    Andersson, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Structural and functional studies of platelet-derived growth factor1994Doktoravhandling, med artikler (Annet vitenskapelig)
  • 43.
    Andersson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Human transplantation antigens: studies on their genetic polymorphism and on viral regulation of their expression1986Doktoravhandling, med artikler (Annet vitenskapelig)
  • 44.
    Andersson, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Self reactivity and tolerance in the immune system: studies on T cells in murine type II collagen-induced arthritis1990Doktoravhandling, med artikler (Annet vitenskapelig)
  • 45.
    Andersson, Sven E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Sensory neuropeptides: species variations in effects on the blood-aqueous barrier, regional blood flows and pupillary sphincter muscle1990Doktoravhandling, med artikler (Annet vitenskapelig)
  • 46.
    Andersson, Swen-Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Epidemiological studies on prostate cancer1996Doktoravhandling, med artikler (Annet vitenskapelig)
  • 47.
    Andersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Studies in tardive dyskinesia1988Doktoravhandling, med artikler (Annet vitenskapelig)
  • 48.
    Andræ, Johanna
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    PDGF in cerebellar development and tumorigenesis2001Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Medulloblastoma is a highly malignant cerebellar childhood tumor. As in many other brain tumors, expression of platelet-derived growth factor (PDGF) and its receptors has been shown in medulloblastoma. To reveal the importance of this growth factor in cerebellar development and tumorigenesis, analyses were performed on human medulloblastoma cell lines and on tissue from normal mouse brain at different stages of development. The in vivo effect of a forced expression of PDGF-B in the cerebellar primordium was examined in transgenic mice.

    In the normal mouse embryo, we found PDGF receptor-α-positive cells in the early neuroepithelium and on neuronal precursors. In the postnatal cerebellum, cells in the external germinal layer and Purkinje cells expressed the receptor. In the medulloblastoma cells, expression of all the three PDGF isoforms and PDGF receptors was seen and correlated to neuronal differentiation. Endogenously activated, i.e. tyrosine phosphorylated, PDGF receptors were identified. To reveal the role of PDGF in normal cerebellar development, we established transgenic mice where a PDGF-B cDNA was introduced via homologous recombination into the engrailed-1 gene. Engrailed-1 is specifically expressed at the mid-/hindbrain boundary of the early neural tube, i.e. in an area from which the cerebellar primordium develops. The ectopic expression of PDGF-B caused a disturbance of cerebellar development. Midline fusion of the cerebellar primordium did not occur properly, which resulted in cerebellar dysplasia in the adult mouse.

    In a parallel study, the expression pattern of a glial fibrillary acidic protein (GFAP)-lacZ transgene was followed in the embryonic mouse central nervous system. It was shown that the human GFAP promoter was already active by embryonic day 9.5 and as development proceeded, expression occured in different, independent cell populations. Among these cell populations were the radial glial cells in the neocortex.

    Fulltekst (pdf)
    FULLTEXT01
  • 49.
    Andrén, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Left ventricular morphology and function in a population sample of elderly men: an echocardiographic study1996Doktoravhandling, med artikler (Annet vitenskapelig)
  • 50.
    Andrén, Maria
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    The Role of Fc Gamma Receptors in Experimental Arthritis2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Induction of collagen-induced arthritis (CIA), an animal model for human rheumatoid arthritis, is dependent on anti-collagen type II (CII) antibodies. The effector mechanism by which autoantibodies contribute to inflammatory reactions in autoimmune diseases is not well understood. In this thesis I have studied the effector pathways used by IgG anti-CII antibodies to initiate arthritis, namely the IgG Fc receptors (FcγRs) and the complement system. We have found that FcγRIII is crucial for development of CIA, as CII-immunized mice lacking this receptor do not develop arthritis and IgG1 and IgG2b anti-CII antibodies require FcγRIII to trigger arthritis when transferred to naïve mice. The antibody-mediated arthritis was further enhanced in mice deficient in the inhibitory FcγRIIB, indicating that FcγRIIB regulates the activation of FcγRIII. Furthermore, we demonstrate that FcγRIII exist as three distinct haplotypes in mice, FcγRIII:H, FcγRIII:V and FcγRIII:T. Mice expressing the FcγRIII:H haplotype are more susceptible to CIA than mice expressing the FcγRIII:V haplotype, indicating that certain FcγRIII haplotype predisposes for CIA. We also show that the most likely FcγRIII-expressing effector cell in CIA is the macrophage, since FcγRIII-expressing macrophages exclusively can induce arthritis in FcγRIII-deficient mice challenged for CIA.

    The complement system was also investigated in development of CIA. We found that this effector pathway is also necessary for onset of arthritis, as CIA was inhibited by treatment with anti-complement factor 5 (C5) antibodies. C5-deficient mice could neither develop CIA unless provided with C5-containing sera.

    Taken together, the work presented in this thesis indicates that FcγRs and the complement system are crucial for the induction of experimental arthritis. These findings are important for understanding the mechanisms behind rheumatoid arthritis and blocking of these effector pathways may in the future be used as treatment of rheumatoid arthritis.

    Delarbeid
    1. Expression of FcγRIII is required for development of collagen-induced arthritis
    Åpne denne publikasjonen i ny fane eller vindu >>Expression of FcγRIII is required for development of collagen-induced arthritis
    Vise andre…
    2002 Inngår i: European Journal of Immunology, Vol. 32, s. 2915-2922Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-92480 (URN)
    Tilgjengelig fra: 2005-01-14 Laget: 2005-01-14bibliografisk kontrollert
    2. FcγRIII-expressing macrophages are essential for the development of collagen-induced arthritis
    Åpne denne publikasjonen i ny fane eller vindu >>FcγRIII-expressing macrophages are essential for the development of collagen-induced arthritis
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-92481 (URN)
    Tilgjengelig fra: 2005-01-14 Laget: 2005-01-14 Sist oppdatert: 2010-01-13bibliografisk kontrollert
    3. Induction of arthritis by single monoclonal IgG anti-collagen type II antibodies and enhancement of arthritis in mice lacking inhibitory FcγRIIB
    Åpne denne publikasjonen i ny fane eller vindu >>Induction of arthritis by single monoclonal IgG anti-collagen type II antibodies and enhancement of arthritis in mice lacking inhibitory FcγRIIB
    Vise andre…
    2003 Inngår i: European Journal of Immunology, Vol. 33, s. 2269-2277Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-92482 (URN)
    Tilgjengelig fra: 2005-01-14 Laget: 2005-01-14bibliografisk kontrollert
    4. IgG Fc receptor polymorphisms and C5 influence susceptibility to collagen-induced arthritis
    Åpne denne publikasjonen i ny fane eller vindu >>IgG Fc receptor polymorphisms and C5 influence susceptibility to collagen-induced arthritis
    Artikkel i tidsskrift (Fagfellevurdert) Submitted
    Identifikatorer
    urn:nbn:se:uu:diva-92483 (URN)
    Tilgjengelig fra: 2005-01-14 Laget: 2005-01-14bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
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