uu.seUppsala University Publications
Change search
Refine search result
1234 151 - 179 of 179
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 151.
    Stridsberg, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Pettersson, Ann
    Hagman, Ragnvi
    Westin, Christoffer
    Höglund, Odd
    Chromogranins can be measured in samples from cats and dogs2014In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 7, article id 336Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Methods for objective evaluation of stress in animals are important, but clinically difficult. An alternative method to study the sympathetic activity may be to investigate Chromogranin A (CGA), Chromogranin B (CGB) and Secretogranin II (SG2). The aim of this study was to investigate the cross-reactivity of CGA, CGB and SG2 between man, cat and dog and to explore possibilities to measure these proteins in samples from cats and dogs.

    RESULTS: Adrenal gland extracts from feline and canine species were measured by region-specific radioimmunoassays in different dilution steps to explore possible inter species cross reactivity. High cross reactivity was found for cats in the CGA17-38, CGA324-337, CGA361-372, CGB and SG2 assays. High cross reactivity was found for dogs in the CGA17-38, CGA361-372, CGB and SN assays. The method measuring the intact CGA was not useful for measurements in cats and dogs.

    CONCLUSIONS: Region-specific assays measuring defined parts of CGA, CGB and SG2 can be used for measurements in samples from cats and dogs. These results are promising and will allow for further studies of these proteins as possible clinical biomarkers in cats and dogs.

  • 152.
    Stridsberg, Mats
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Clinical Chemstry.
    Tiensuu Janson, Eva
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Portela-Gomes, Guida M.
    Department of Genetics and Pathology.
    Cellular localisation of chromogranins and processed products in the diffuse neuroendocrine system and related tumours2004In: Curr. Med. Chem., Vol. 4, p. 149-160Article in journal (Refereed)
  • 153.
    Stridsberg, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tjälve, Hans
    Wilander, Erik
    Whole-body autoradiography of 123I-labelled islet amyloid polypeptide (IAPP) Accumulation in the lung parenchyma and in the villi of the intestinal mucosa in rats1993In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 32, no 2, p. 155-9Article in journal (Other academic)
    Abstract [en]

    Islet amyloid polypeptide (IAPP) in a 37 amino-acid pancreatic islet polypeptide, displaying about 50% amino-acid homology with neuropeptide calcitonin gene-related peptide (CGRP). IAPP is co-stored with insulin in the beta-cell secretory granules and co-released with insulin upon stimulation. Human IAPP has the ability to precipitate in the shape of amyloid in patients with type II (non-insulin dependent) diabetes but otherwise its functional or pathophysiological role is enigmatic. In the present study 125I-labelled rat IAPP was injected i.v. into female Sprague-Dawley rats and the distribution of the peptide was examined by whole-body autoradiography at intervals from 2 to 30 min after administration. Already after 2 min high radioactivity occurred in the lung parenchyma and in the villi of the small intestinal mucosa. The high radioactivity in these tissues persisted at 10 min but at 30 min the radioactive labelling had decreased to a level only slightly higher than that observed in the blood. A high uptake of radioactivity was also seen in the cortex of the kidney. In other tissues, including the liver, the skeletal muscle, and the exocrine and endocrine pancreas, the radioactivity was low and did not exceed that of the blood. The uptake of 125I-IAPP in the lungs and in the small intestine was inhibited by simultaneous injections of either an excess of unlabelled rat IAPP or unlabelled rat CGRP. This indicates that the labelled structures observed in the lung and the small intestine after injection of 125I-IAPP alone was due to binding to receptors for IAPP or CGRP in these tissues. The accumulation of radioactivity in the kidneys was not affected by pretreatment with high doses of unlabelled IAPP or CGRP. This unspecific uptake of radioactivity may be due to reabsorption of labelled IAPP in the proximal tubuli. Our results indicate the presence of receptors binding IAPP in the lung parenchyma and in the villi of the small intestinal mucosa. This, in turn, may imply prominent biological activities of IAPP at these sites.

  • 154.
    Sundberg, Isak
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Ramklint, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Papadopoulos, Fotios C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Cunningham, Janet L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Salivary Melatonin in Relation to Depressive Symptom Severity in Young Adults.2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 4, article id e0152814Article in journal (Refereed)
    Abstract [en]

    Reduced levels of melatonin have been associated with severe depression. The aim was to investigate the correlation between salivary melatonin and dimensional measures of depressive symptom severity in young adult psychiatric patients. Levels of melatonin were analyzed in six saliva samples during waking hours from 119 young adult patients under outpatient psychiatric care. Melatonin levels were tested for association with the severity of depressive symptoms using the self-rating version of the Montgomery Åsberg Depression Rating Scale (MADRS-S). Where possible, depressive symptoms were assessed again after 6±2 months of treatment. Response was defined as decrease in MADRS-S by ≥50% between baseline and follow-up. Patients with levels of melatonin in the lowest quartile at bedtime had an increased probability of a high MADRS-S score compared to those with the highest levels of melatonin (odds ratio 1.39, 95% CI 1.15-1.69, p<0.01). A post hoc regression analysis found that bedtime melatonin levels predicted response (odds ratio 4.4, 95% CI 1.06-18.43, p<0.05). A negative relationship between salivary melatonin and dimensional measures of depressive symptom severity was found in young patients under outpatient psychiatric care. Bedtime salivary melatonin levels may have prognostic implications.

  • 155.
    Sundin, J.
    et al.
    Gothenburg Univ, Dept Internal Med, Gothenburg, Sweden..
    Bennet, S.
    Gothenburg Univ, Dept Internal Med, Gothenburg, Sweden..
    Le Neve, B.
    Danone Nutricia Res, Palaiseau, France..
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Tornblom, H.
    Gothenburg Univ, Dept Internal Med, Gothenburg, Sweden..
    Ohman, L.
    Gothenburg Univ, Dept Internal Med, Gothenburg, Sweden..
    Simren, M.
    Gothenburg Univ, Dept Internal Med, Gothenburg, Sweden..
    Increased fecal levels of granins in IBS patients: relationship to symptoms and intestinal inflammation?2016In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 28, p. 44-44Article in journal (Other academic)
  • 156. Sundqvist, Pernilla
    et al.
    Feuk, Ulla
    Häggman, Mikael
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Urologi.
    Persson, A Erik G
    Department of Medical Cell Biology.
    Stridsberg, Mats
    Department of Medical Sciences. Clinical Chemstry.
    Wadström, Jonas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Hand-assisted retroperitoneoscopic live donor nephrectomy in comparison to open and laparoscopic procedures: a prospective study on donor morbidity and kidney function.2004In: Transplantation, ISSN 0041-1337, Vol. 78, no 1, p. 147-53Article in journal (Refereed)
  • 157. Svartberg, J
    et al.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Andersson, D
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Tumour-induced hypoglycaemia in a patient with insulin-dependent diabetes mellitus1996In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 239, no 2, p. 181-185Article in journal (Refereed)
    Abstract [en]

    We report on a case of malignant insulinoma occurring in a patient with genuine insulin-dependent diabetes mellitus (IDDM). A review of cases concerning patients with diabetes mellitus and insulinomas is presented, and reveals only patients with non-insulin-dependent diabetes mellitus (NIDDM). Our case appears to be the first in showing the combination of IDDM and a functioning malignant insulinoma.

  • 158.
    Swenne, Ingemar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Bone metabolism in adolescent girls with eating disorders and weight loss: independent effects of weight change, insulin-like growth factor-1 and oestradiol2015In: Eating and Weight Disorders, ISSN 1124-4909, E-ISSN 1590-1262, Vol. 20, no 1, p. 33-41Article in journal (Refereed)
    Abstract [en]

    Adolescents with eating disorders (ED) are at risk of developing osteoporosis if weight is not recovered. Previous investigations do not separate the effects of weight change per se from those of concomitant hormonal changes. In this investigation serum osteocalcin (OC), C-terminal telopeptide of collagen (CTX), insulin-like growth factor-1 (IGF-1) and oestradiol were measured at assessment of 498 girls with ED and during weight gain of 59 girls. At assessment, OC concentrations were associated independently with weight (change), IGF-1 and oestradiol. Low weight, a high rate of weight loss and the hormone concentrations were associated with low OC. Low weight and high rate of weight loss were associated with high CTX concentrations but there were no associations independent of weight (change) with the hormones. During weight recovery, OC and CTX were independently and positively associated with weight, weight gain, IGF-1 and oestradiol. Bone metabolism markers are related to weight change independently of IGF-1 and oestradiol during both weight loss and weight gain. During weight gain, when pubertal development and growth are resumed there is an additional independent positive association between the markers and IGF-1 and oestradiol. These relationships are strongest in premenarcheal girls.

  • 159.
    Swenne, Ingemar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Bone metabolism markers in adolescent girls with eating disorders and weight loss: effects of growth, weight trend, developmental and menstrual status2012In: Archives of Osteoporosis, ISSN 1862-3514, Vol. 7, no 1-2, p. 125-133Article in journal (Refereed)
    Abstract [en]

    SUMMARY:

    Serum concentrations of osteocalcin (OC) decrease and those of C-terminal telopeptide of type 1 collagen (CTX) increase during weight loss in adolescent girls with eating disorders (ED). The impact of weight loss on bone metabolism markers is greatest in premenarcheal girls.

    INTRODUCTION:

    Adolescents with ED stand a risk of not reaching optimal peak bone mass and develop osteoporosis. Previous investigations are contradictory as to how markers of bone formation and resorption change during weight loss and nutritional rehabilitation.

    METHODS:

    Serum OC and CTX were measured at assessment of 461 adolescent girls with ED and during treatment of 55 girls with anorexia nervosa. Bone metabolism was related to weight, weight change and growth rate.

    RESULTS:

    At assessment, OC concentrations were positively correlated with growth rate and inversely with age and (rate of) weight loss. Growth rate was the only predictor of CTX concentrations in premenarcheal girls. In postmenarcheal girls, CTX concentrations were inversely correlated with age and rate of weight loss. During weight gain, there was an increase of OC concentrations. CTX concentrations decreased at the onset of weight gain and increased when near normal weight was reached.

    CONCLUSIONS:

    Bone formation markers decrease and resorption markers increase during weight loss. The effects are independent of menstrual status but the impact on bone formation markers is greater in young, premenarcheal girls. Markers are normalised during weight gain but it is conceivable that repeated and/or prolonged weight loss in adolescents reduces peak bone mass.

  • 160. Swärd, Christina
    et al.
    Bernhardt, Peter
    Johanson, Viktor
    Schmitt, Anneli
    Ahlman, Hakan
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Forssell-Aronsson, Eva
    Nilsson, Ola
    Kolby, Lars
    Comparison of [177Lu-DOTA0,Tyr3]-Octreotate and [177Lu-DOTA0,Tyr3]-Octreotide for Receptor-Mediated Radiation Therapy of the Xenografted Human Midgut Carcinoid Tumor GOT12008In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 23, no 1, p. 114-120Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare the tumor uptake versus time and the tumor response in nude mice transplanted with a human midgut carcinoid (GOT1), when treated with either [177Lu-DOTA0,Tyr3]-octreotide or [177Lu-DOTA0,Tyr3]-octreotate and to evaluate if plasma chromogranin A (P-CgA) was a reliable marker of tumor response. The tumor uptake and retention of activity of a single intravenous (i.v.) dose (15 MBq) of [177Lu-DOTA0,Tyr3]-octreotate or [177Lu-DOTA0,Tyr3]-octreotide were compared in nude mice xenografted with GOT1. The activity concentration 24 hours after injection was significantly higher in animals given [177Lu-DOTA0,Tyr3]-octreotate versus [177Lu-DOTA0,Tyr3]-octreotide (16% ± 1.4% of injected activity per gram [%IA/g] vs. 8.1% ± 2.1% IA/g, mean ± standard error of the mean) (p = 0.00061). The mean absorbed dose was higher in animals given [177Lu-DOTA0,Tyr3]-octreotate (46 ± 4.3 vs. 17 ± 3.4 Gy). The reduction of tumor volume was accordingly more prominent in animals given [177Lu-DOTA0,Tyr3]-octreotate than in animals given [177Lu-DOTA0,Tyr3]-octreotide (p = 0.003). The mean tumor volume for animals given [177Lu-DOTA0,Tyr3]-octreotate was reduced to 3% of its initial value. P-CgA values were strongly correlated with tumor volume. Octreotate seems to be a more suitable somatostatin analog than octreotide for receptor-mediated radiation therapy. P-CgA is a simple, accurate method for the estimation of tumor response in this animal model.

  • 161.
    Söderquist, Fanny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Rasmusson, Annica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Alit, Abir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Cunningham, Janet L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Melatonin Immunoreactivity in Malignant Small Intestinal Neuroendocrine Tumours2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, article id e0164354Article in journal (Refereed)
    Abstract [en]

    Background/ Aims Small intestinal neuroendocrine tumours (SI-NETs) are derived from enterochromaffin cells. After demonstrating melatonin in enterochromaffin cells, we hypothesized that SI-NETs may express and secrete melatonin, which may have an impact on clinical factors and treatment response. Methods Tumour tissue from 26 patients with SI-NETs, representing paired sections of primary tumour and metastasis, were immunohistochemically stained for melatonin and its receptors, MT1 and MT2. Plasma melatonin and immunoreactivity (IR) for melatonin, MT1 and MT2 in tumour cells were compared to other tumour markers and clinical parameters. Melatonin was measured at two time points in fasting morning plasma from 43 patients with SI-NETs. Results Melatonin IR was found in all SI-NETS. Melatonin IR intensity in primary tumours correlated inversely to proliferation index (p = 0.022) and patients reported less diarrhoea when melatonin IR was high (p = 0.012). MT1 IR was low or absent in tumours. MT2 expression was medium to high in primary tumours and generally reduced in metastases (p = 0.007). Plasma-melatonin ranged from 4.5 to 220.0 pg/L. Higher levels were associated with nausea at both time points (p = 0.027 and p = 0.006) and flush at the second sampling. In cases with disease stabilization or remission (n = 34), circulating melatonin levels were reduced in the second sample (p = 0.038). Conclusion Immunoreactive melatonin is present in SI-NETs. Circulating levels of melatonin in patients with SI-NETs are reduced after treatment. Our results are congruent with recent understanding of melatonin's endocrine and paracrine functions and SI-NETs may provide a model for further studies of melatonin function.

  • 162. Tartaglia, Andreas
    et al.
    Portela-Gomes, Guida M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Oberg, Kjell
    Department of Medical Sciences. Onkologisk endokrinologi.
    Vezzadini,
    Foschini,
    Stridsberg, Mats
    Department of Medical Sciences. Clinical Chemistry.
    Chromogranin A in gastric neuroendocrine tumours: an immunohistochemical and biochemical study with region-specific antibodies.2006In: Virchows Arch, ISSN 0945-6317, p. 1-8Article in journal (Refereed)
  • 163. Tiensuu Janson, E
    et al.
    Stridsberg, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Gobl, A
    Westlin, J E
    Oberg, K
    Determination of somatostatin receptor subtype 2 in carcinoid tumors by immunohistochemical investigation with somatostatin receptor subtype 2 antibodies.1998In: Cancer Res, ISSN 0008-5472, Vol. 58, no 11, p. 2375-8Article in journal (Other scientific)
  • 164.
    Tiensuu Janson, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Theodorsson, E
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center1997In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 8, no 7, p. 685-690Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Little is known about factors related to prognosis in patients with carcinoid disease. In this study we have tried to identify such factors.

    PATIENTS AND METHODS:

    We have evaluated 301 consecutive carcinoid patients (256 midgut, 39 foregut and six hindgut) referred during 15 years for medical treatment with respect to tumor distribution, hormone production, prognostic factors and survival.

    RESULTS:

    Survival was significantly shorter in midgut carcinoid patients with > or = 5 liver metastases or with high levels of urinary 5-hydroxyindoleacetic acid, plasma chromogranin A or neuropeptide K. By univariate analysis, these variables together with the presence of carcinoid syndrome were related to a higher risk of dying. In multivariate analyses, performed in the 71 patients with full information on all variables, advanced age and plasma chromogranin A > 5000 micrograms/l were independent predictors of overall survival.

    CONCLUSIONS:

    Poor prognostic factors for midgut carcinoid patients were multiple liver metastases, presence of carcinoid syndrome and high levels of the tumor markers studied. In this study the only independent predictors of bad prognosis in midgut, carcinoid patients were advanced age, which however is inherently related to overall survival, and plasma chromogranin A > 5000 micrograms/l. Thus, chromogranin A may prove to be an important prognostic marker for patients with carcinoid tumors.

  • 165.
    Tsolakis, Apostolos V.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Granerus, Goran
    Linkoping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden..
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Falkmer, Sture E.
    Ryhov Cty Hosp, Dept Pathol, SE-55185 Jonkoping, Sweden..
    Janson, Eva T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 47, p. 13240-13249Article in journal (Refereed)
    Abstract [en]

    AIM:

    To study histidine decarboxylase (HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite.

    METHODS:

    Control tissues from fundus (n = 3) and corpus (n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours (GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2 (VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid (U-MeImAA) was determined using high-performance liquid chromatography in 27 of the 64 patients.

    RESULTS:

    In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cell population co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-MeImAA excretion was detected, but only two of the patients exhibited related endocrine symptoms.

    CONCLUSION:

    Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Co-expression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.

  • 166.
    Tsolakis, Apostolos V.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Falkmer, Sture E.
    Waldum, Helge L.
    Saras, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Obestatin/ghrelin cells in normal mucosa and endocrine tumours of the stomach2009In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 160, no 6, p. 941-949Article in journal (Refereed)
    Abstract [en]

    Objective:

    Obestatin and ghrelin are derived from the same gene and co-expressed in the same endocrine cells. Vesicular monoamine transporter-2 (VMAT-2), a marker for enterochromaffin-like (ECL) cells, is considered to be expressed in ghrelin cells. The aim was to establish if the two peptides and the transporter are co-expressed, both in normal gastric mucosa and in gastric endocrine tumours.

    Design:

    An immunohistochemical study was performed on gastric biopsy material and on surgical specimens from 63 patients with gastric endocrine tumours and from individuals with normal gastric mucosa. Cells displaying obestatin immunoreactivity were examined regarding co-localization with ghrelin and VMAT-2. Both single- and double-immunostaining techniques were applied. Obestatin concentration in blood was measured in a subgroup of these patients. The results were correlated to various clinico-pathological parameters.

    Results:

    In the normal mucosa, obestatin/ghrelin-immunoreactive cells rarely co-expressed VMAT-2. In most tumour tissue specimens, only a fraction of neoplastic cells displayed immunoreactivity to obestatin, and these cells always co-expressed ghrelin. Neoplastic obestatin-/ ghrelin-IR cells invariably expressed VMAT-2, except for two ghrelinomas. The obestatin concentrations in blood were consistently low and did not correlate to clinico-pathological data.

    Conclusions:

    Obestatin and ghrelin immunoreactivity always occurred in the same endocrine cells in the gastric mucosa but these cells only occasionally co-expressed VMAT-2, opposite to the findings in tumours. These results indicate that endocrine cells expressing obestatin and ghrelin mainly differ from VMAT-2 expressing cells (ECL-cells) and can develop into pure ghrelinomas. Plasma concentrations of obestatin did not correlate to cellular expression.

  • 167. Vaahersalo, Jukka
    et al.
    Skrifvars, Markus B.
    Pulkki, Kari
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Rosjo, Helge
    Hovilehto, Seppo
    Tiainen, Marjaana
    Varpula, Tero
    Pettila, Ville
    Ruokonen, Esko
    Admission interleukin-6 is associated with post resuscitation organ dysfunction and predicts long-term neurological outcome after out-of-hospital ventricular fibrillation2014In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 85, no 11, p. 1573-1579Article in journal (Refereed)
    Abstract [en]

    Aim of the study: To study plasma concentrations of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and S-100B during intensive care after out-of-hospital cardiac arrest from ventricular fibrillation (OHCA-VF), and their associations with the duration of ischemia, organ dysfunction and long-term neurological outcome.

    Materials and methods: A 12-month prospective observational multicentre study was conducted in 21 Finnish intensive care units in 2011. IL-6, hs-CRP and S-100B were measured at 0-6 h, 24 h, 48 h and 96 h after ICU admission. Associations with the time to return of spontaneous circulation (ROSC), sequential organ failure assessment (SOFA) scores divided into tertiles and 12-month cerebral performance category (CPC) were tested.

    Results: Of 186 OHCA-VF patients included in the study, 110 (59.1%) patients survived with good neurological outcome (CPC 1-2) 12 months after cardiac arrest. Admission plasma concentrations of IL-6 but not hs-CRP were higher with prolonged time to ROSC (p < 0.001, 0.203, respectively), in patients with subsequent higher SOFA scores (p < 0.001, 0.069) and poor long-term neurological outcome (CPC 3-5) (p < 0.001, 0.315). S-100B concentrations over time were higher in patients with CPC of 3-5 (p < 0.001). The area under the curve for prediction of poor 12-month outcome for admission levels was 0.711 IL6, 0.663 for S-100B and 0.534 for hs-CRP. With multivariate logistic regression analysis only admission IL-6 (p = 0.046, OR 1.006, 95% CI 1.000-1.011/ng/L) was an independent predictor of poor neurological outcome.

    Conclusion: Admission high IL-6, but not hs-CRP or S-100B, is associated with extra-cerebral organ dysfunction and along with age and time to ROSC are independent predictors for 12-month poor neurologic outcome (CPC 3-5).  

  • 168.
    Wagner, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Peterson, Christer G B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lampinen, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Increased Fecal Levels of Chromogranin A, Chromogranin B and Secretoneurine in Collagenous Colitis2013In: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 36, no 4, p. 855-861Article in journal (Refereed)
    Abstract [en]

    Interactions between the enteric nervous system and the immune system are suggested to play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aims to determine if chromogranin A (CgA), chromogranin B (CgB), and secretoneurin (SN) are detectable in feces (F) from patients with collagenous colitis (CC) and to compare the levels found in patients with ulcerative colitis (UC) and Crohn’s disease (CD) before and during treatment. Patients with CC (n = 12) were studied before and after 3, 7, 28, and 56 days of treatment. Patients with IBD (UC, n = 21; CD, n = 11) were studied before and after 28 and 56 days of treatment. Clinical data were recorded, and fecal samples were collected at each occasion. F-CgA, F-CgB, and F-SN were measured by RIA. Eleven patients with CC, 21 with UC, and 10 with CD achieved remission. On inclusion, CC patients had higher levels of F-CgA, F-CgB, and F-SN than patients with IBD and controls. Patients with IBD expressed markedly lower levels of F-SN than controls. During treatment, F-SN in CC patients decreased to control levels but remained low in IBD patients. No change was found in F-CgA or F-CgB in any of the groups. In conclusion, CgA, CgB, and SN are detectable in feces, and CC patients express higher values than patients with IBD and controls. During treatment, F-SN decreased to control levels in CC. These findings suggest that the enteric nervous system is clearly involved in the pathophysiology of CC.

  • 169.
    Wallentin, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ärnström, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Husted, Steen
    Hosp Unit West, Dept Med, Herning Holstebro, Denmark..
    Janzon, Magnus
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.;Linkoping Univ, Div Hlth Care Anal, Dept Med & Hlth Sci, Ctr Med Technol Assessment, Linkoping, Sweden..
    Johnsen, Sören Paaske
    Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark..
    Kontny, Frederic
    Stavanger Univ Hosp, Dept Cardiol, Stavanger, Norway.;Drammen Heart Ctr, Drammen, Norway..
    Kempf, Tibor
    Hannover Med Sch, Dept Cardiol & Angiol, Hannover, Germany..
    Levin, Lars-Åke
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.;Linkoping Univ, Div Hlth Care Anal, Dept Med & Hlth Sci, Ctr Med Technol Assessment, Linkoping, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Wollert, Kai C.
    Hannover Med Sch, Dept Cardiol & Angiol, Hannover, Germany..
    Swahn, Eva
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised, multicentre study2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, no 10054, p. 1903-1911Article in journal (Refereed)
    Abstract [en]

    Background The FRISC-II trial was the first randomised trial to show a reduction in death or myocardial infarction with an early invasive versus a non-invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome. Here we provide a remaining lifetime perspective on the effects on all cardiovascular events during 15 years' follow-up. Methods The FRISC-II prospective, randomised, multicentre trial was done at 58 Scandinavian centres in Sweden, Denmark, and Norway. Between June 17, 1996, and Aug 28, 1998, we randomly assigned (1:1) 2457 patients with non-ST-elevation acute coronary syndrome to an early invasive treatment strategy, aiming for revascularisation within 7 days, or a non-invasive strategy, with invasive procedures at recurrent symptoms or severe exercise-induced ischaemia. Plasma for biomarker analyses was obtained at randomisation. For long-term outcomes, we linked data with national health-care registers. The primary endpoint was a composite of death or myocardial infarction. Outcomes were compared as the average postponement of the next event, including recurrent events, calculated as the area between mean cumulative count-of-events curves. Analyses were done by intention to treat. Findings At a minimum of 15 years' follow-up on Dec 31, 2014, data for survival status and death were available for 2421 (99%) of the initially recruited 2457 patients, and for other events after 2 years for 2182 (89%) patients. During follow-up, the invasive strategy postponed death or next myocardial infarction by a mean of 549 days (95% CI 204-888; p= 0.0020) compared with the non-invasive strategy. This effect was larger in non-smokers (mean gain 809 days, 95% CI 402-1175; p(interaction) = 0.0182), patients with elevated troponin T (778 days, 357-1165; p (interaction) = 0.0241), and patients with high concentrations of growth differentiation factor-15 (1356 days, 507-1650; p (interaction) = 0.0210). The difference was mainly driven by postponement of new myocardial infarction, whereas the early difference in mortality alone was not sustained over time. The invasive strategy led to a mean of 1128 days (95% CI 830-1366) postponement of death or next readmission to hospital for ischaemic heart disease, which was consistent in all subgroups (p< 0.0001). Interpretation During 15 years of follow-up, an early invasive treatment strategy postponed the occurrence of death or next myocardial infarction by an average of 18 months, and the next readmission to hospital for ischaemic heart disease by 37 months, compared with a non-invasive strategy in patients with non-ST-elevation acute coronary syndrome. This remaining lifetime perspective supports that an early invasive treatment strategy should be the preferred option in most patients with non-ST-elevation acute coronary syndrome.

  • 170.
    Welin, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lavenius, Erik
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours2004In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 151, no 1, p. 107-112Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    High-dose somatostatin analogue treatment has shown an antiproliferative effect in one study including patients with neuroendocrine tumours. To explore this therapeutic strategy further, we have studied the effect of a high-dose formula of octreotide, octreotide pamoate, in midgut carcinoid patients.

    DESIGN AND METHODS:

    Twelve patients with advanced midgut carcinoid tumours with a median duration of disease of more than 5 years were included. All were in a progressive state despite several previous treatment modalities. Octreotide pamoate (160 mg) was given as an intramuscular injection every 2 weeks for 2 months and then monthly. Radiological and biochemical responses were monitored.

    RESULTS:

    Tumour size and biochemical markers were stabilised for a median of 12 months in 75% of the patients. Ten patients had symptomatic improvement of flush and diarrhoea.

    CONCLUSION:

    In this group of patients with advanced midgut carcinoid tumours and progressive disease, octreotide pamoate managed to improve symptoms, and stabilise hormone production and tumour growth in 75% of the patients. We believe that high-dose treatment with somatostatin analogues can be an important addition to the therapeutic arsenal for patients with advanced progressive midgut carcinoid tumours.

  • 171.
    Welin, Staffan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Elevated Plasma Chromogranin A is the First Indication of Recurrence in Radically Operated Midgut Carcinoid Tumours2009In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 89, no 3, p. 302-307Article in journal (Refereed)
    Abstract [en]

    Background:

    Patients with malignant midgut carcinoids are occasionally diagnosed with limited tumor spread, and surgery with radical intention is performed. Despite curative intent, recurrences occur frequently, motivating long-term biochemical and radiological follow-up. This study aimed to compare the usefulness of various methods in detecting such recurrences.

    Methods:

    This retrospective study included 56 patients with radically operated midgut carcinoids referred to our University Hospital for evaluation and follow-up between 1985 and 2004. Patients were monitored 1-3 times per year using plasma-chromogranin A (P-CgA), urinary 5-hydroxyindoleacetic acid (U-5HIAA) concentrations as well as radiological examinations, including ultrasonography, computerized tomography or magnetic resonance investigation. In a subset of cases, somatostatin receptor scintigraphy and/or positron emission tomography with 5-hydroxytryptophan was performed. Time from operation until established recurrence was recorded.

    Results:

    Tumor recurrence was established in 33 of 56 patients after a median of 32 months (range 6-217). Elevated P-CgA was the first marker to become pathologically elevated in 28 of these 33 patients (85%). In 3 of these 28 patients, radiology was simultaneously positive for a recurrence.

    Conclusion:

    P-CgA was the first marker to indicate tumor recurrence in the majority of radically operated midgut carcinoid patients. To avoid unnecessary and costly examinations in asymptomatic patients, we suggest that follow-up should comprise measurements of P-CgA twice a year and annual ultrasonography until P-CgA is elevated or clinical symptoms occur, at which time all efforts should be made to identify recurrent tumor lesions in order to give the patient the best possible treatment which, if possible, should be surgical removal of the recurrence.

  • 172. Wen, Gen
    et al.
    Mahata, Sushil K
    Cadman, Peter
    Mahata, Manjula
    Ghosh, Sajalendu
    Mahapatra, Nitish R
    Rao, Fangwen
    Stridsberg, Mats
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Smith, Douglas W
    Mahboubi, Payam
    Schork, Nicholas J
    O'Connor, Daniel T
    Hamilton, Bruce A
    Both rare and common polymorphisms contribute functional variation at CHGA, a regulator of catecholamine physiology.2004In: Am J Hum Genet, ISSN 0002-9297, Vol. 74, no 2, p. 197-207Article in journal (Other scientific)
  • 173. Wen, Gen
    et al.
    Wessel, Jennifer
    Zhou, Weidong
    Ehret, Georg B
    Rao, Fangwen
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Mahata, Sushil K.
    Gent, Peter M.
    Das, Madhusudan
    Cooper, Richard S.
    Chakravarti, Aravinda
    Zhou, Huilin
    Schork, Nicholas J.
    O'connor, Daniel T.
    Hamilton, Bruce A.
    An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension2007In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 16, no 14, p. 1752-1764Article in journal (Refereed)
    Abstract [en]

    Granins regulate secretory vesicle formation in neuroendocrine cells and granin-derived peptides are co-released with neurotransmitters as modulatory signals at sympathetic sites. We report evidence for association between a regulatory polymorphism in Secretogranin II (SCG2) and hypertension in African-American subjects. The minor allele is ancestral in the human lineage and is associated with disease risk in two case-control studies and with elevated blood pressure in a separate familial study. Mechanistically, the ancestral allele acts as a transcriptional enhancer in cells that express endogenous Scg2, whereas the derived allele does not. ARIX (PHOX2A) and PHOX2B are identified as potential transactivating factors by oligonucleotide affinity chromatography and mass spectrometry and confirmed by chromatin immunoprecipitation. Each of these transcription factors preferentially binds the risk allele, both in vitro and in vivo. Population genetic considerations suggest positive selection of the protective allele within the human lineage. These results identify a common regulatory variation in SCG2 and implicate granin gene expression in the control of human blood pressure and susceptibility to hypertension.

  • 174.
    Westerberg, Per-Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Tobias E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Regulation of fibroblast growth factor-23 in chronic kidney disease2007In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 22, no 11, p. 3202-3207Article in journal (Refereed)
    Abstract [en]

    Background

    Fibroblast growth factor-23 (FGF23) is a circulatingfactor that regulates the renal reabsorption of inorganic phosphate(Pi) and is increased in chronic kidney disease (CKD). The aimof the current investigation was to study the regulation ofFGF23 in CKD subjects with various degree of renal function.As such, we analysed the relationship between FGF23, Pi, calcium,parathyriod hormone (PTH), 25(OH) vitamin D3(25(OH)D3), 1,25(OH)2vitamin D3(1,25(OH)2D3) and estimated glomerular filtrationrate (eGFR).

    Methods

    Intact FGF23 and other biochemical variables were analysedin 72 consecutive adult out-patients with various stages ofCKD (eGFR ranging from 4–96 ml/min.) Association studieswere performed using linear univariate and multivariate analysis.

    Results

    FGF23 was significantly elevated at CKD stage 4 (266± 315 pg/ml, P < 0.001) and 5 (702 ± 489 pg/ml,P < 0.001) compared with CKD 1–2 (46 ± 43 pg/ml).In CKD 4–5 an independent association between log FGF23and Pi (P < 0.001), 25(OH)D3 (P < 0.05) as well as eGFR(P < 0.01) was observed. In contrast, in CKD 1–3 logPTH (P < 0.05) was the only independent predictor of logFGF23 in multivariate analysis. In CKD 1–5, Pi (P <0.00001) and log PTH (P < 0.01) were explanatory variablesfor log FGF23 in multivariate analysis.

    Conclusions

    We conclude that serum FGF23 increases in CKD 4–5,in parallel with the emerging hyperphosphataemia. Serum Pi isthe most important predictor of FGF23 when GFR is less than30 ml/min. In contrast, our data suggest that Pi may not bean important determinant of FGF23 in normophosphataemic CKDsubjects. Finally, the association between FGF23 and PTH inCKD may suggest a co-regulation that remains to be further elucidated.

  • 175. Willis, Michael
    et al.
    Prokesch, Manuela
    Hutter-Paier, Birgit
    Windisch, Manfred
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Mahata, Sushil K.
    Kirchmair, Rudolf
    Wietzorrek, Georg
    Knaus, Hans-Günther
    Jellinger, Kurt
    Humpel, Christian
    Marksteiner, Josef
    Chromogranin B and Secretogranin II in transgenic mice overexpressing human APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in Alzheimer patients2008In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 13, no 2, p. 123-135Article in journal (Refereed)
    Abstract [en]

    Chromogranin B and secretogranin II are major soluble constituents of large dense core vesicles of presynaptic structures and have been found in neuritic plaques of Alzheimer patients. We examined the distribution and expression of these peptides in both transgenic mice over expressing human amyloid-beta protein precursor APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in human post-mortem brain. In transgenic mice, the number of amyloid-beta plaques and chromogranin immunopositive plaques increased from 6 to 12 months. About 60% of amyloid-beta plaques were associated with chromogranin B and about 40% with secretogranin II. Chromogranin immunoreactivity appeared mainly as swollen dystrophic neurites. Neither synaptophysin- nor glial fibrillary acidic protein- immunoreactivity was expressed in chromogranin immunoreactive structures at any timepoint. Density of chromogranin peptides in hippocampal structures did not change in transgenic animals at any timepoint, even though animals had a poorer performance in the Morris water maze task. In conclusion, our findings in transgenic animals partly resembled findings in Alzheimer patients. Chromogranin peptides were associated with amyloid-beta plaques, but were not reduced in specific brain areas as previously reported by our group. Therefore specific changes of chromogranin peptides observed in Alzheimer patients can be related to amyloid-beta pathology only.

  • 176. Zhang, Kuixing
    et al.
    Rao, Fangwen
    Miramontes-Gonzalez, Jose Pablo
    Hightower, C. Makena
    Vaught, Brian
    Chen, Yuhong
    Greenwood, Tiffany A.
    Schork, Andrew J.
    Wang, Lei
    Mahata, Manjula
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Khandrika, Srikrishna
    Biswas, Nilima
    Fung, Maple M.
    Waalen, Jill
    Middelberg, Rita P.
    Heath, Andrew C.
    Montgomery, Grant W.
    Martin, Nicholas G.
    Whitfield, John B.
    Baker, Dewleen G.
    Schork, Nicholas J.
    Nievergelt, Caroline M.
    O'Connor, Daniel T.
    Neuropeptide Y (NPY): Genetic Variation in the Human Promoter Alters Glucocorticoid Signaling, Yielding Increased NPY Secretion and Stress Responses2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. 1678-1689Article in journal (Refereed)
    Abstract [en]

    Objectives

    This study sought to understand whether genetic variation at the Neuropeptide Y (NPY) locus governs secretion and stress responses in vivo as well as NPY gene expression in sympathochromaffin cells.

    Background

    The NPY is a potent pressor peptide co-released with catecholamines during stress by sympathetic axons. Genome-wide linkage on NPY secretion identified a LOD (logarithm of the odds ratio) peak spanning the NPY locus on chromosome 7p15.

    Methods

    Our approach began with genomics (linkage and polymorphism determination), extended into NPY genetic control of heritable stress traits in twin pairs, established transcriptional mechanisms in transfected chromaffin cells, and concluded with observations on blood pressure (BP) in the population.

    Results

    Systematic polymorphism tabulation at NPY (by re-sequencing across the locus: promoter, 4 exons, exon/intron borders, and untranslated regions; on 2n = 160 chromosomes of diverse biogeographic ancestries) identified 16 variants, of which 5 were common. We then studied healthy twin/sibling pairs (n = 399 individuals), typing 6 polymorphisms spanning the locus. Haplotype and single nucleotide polymorphism analyses indicated that proximal promoter variant ∇−880Δ (2-bp TG/—, Ins/Del, rs3037354) minor/Δ allele was associated with several heritable (h2) stress traits: higher NPY secretion (h2 = 73 ± 4%) as well as greater BP response to environmental (cold) stress, and higher basal systemic vascular resistance. Association of ∇−880Δ and plasma NPY was replicated in an independent sample of 361 healthy young men, with consistent allelic effects; genetic variation at NPY also associated with plasma NPY in another independent series of 2,212 individuals derived from Australia twin pairs. Effects of allele −880Δ to increase NPY expression were directionally coordinate in vivo (on human traits) and in cells (transfected NPY promoter/luciferase reporter activity). Promoter −880Δ interrupts a novel glucocorticoid response element motif, an effect confirmed in chromaffin cells by site-directed mutagenesis on the transfected promoter, with differential glucocorticoid stimulation of the motif as well as alterations in electrophoretic mobility shifts. The same −880Δ allele also conferred risk for hypertension and accounted for approximately 4.5/approximately 2.1 mm Hg systolic BP/diastolic BP in a population sample from BP extremes.

    Conclusions

    We conclude that common genetic variation at the NPY locus, especially in proximal promoter ∇−880Δ, disrupts glucocorticoid signaling to influence NPY transcription and secretion, raising systemic vascular resistance and early heritable responses to environmental stress, eventuating in elevated resting BP in the population. The results point to new molecular strategies for probing autonomic control of the human circulation and ultimately susceptibility to and pathogenesis of cardiovascular and neuropsychiatric disease states.

  • 177. Ärnlöv, J
    et al.
    Lind, L
    Stridsberg, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Andren, B
    Lithell, H
    N-terminal atrial natriuretic peptide and left ventricular geometry and function in a population sample of elderly males.2000In: J Intern Med, ISSN 0954-6820, Vol. 247, no 6, p. 699-708Article in journal (Other scientific)
  • 178.
    Öberg, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Stridsberg, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Neuroendocrine tumors2002In: Tumor markers: physiology, pathobiology, technology and clinical applications, 2002, p. 339-349Chapter in book (Other scientific)
  • 179. Öhman, Lena
    et al.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Isaksson, Stefan
    Jerlstad, Pernilla
    Simrén, Magnus
    Altered Levels of Fecal Chromogranins and Secretogranins in IBS: Relevance for Pathophysiology and Symptoms?2012In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 107, no 3, p. 440-447Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Chromogranins (Cg) and secretogranins (Sg) are proteins ubiquitous in secretory cells of the enteric, endocrine, and immune systems, and may reflect activity of these systems. We therefore performed a hypothesis generating study to evaluate the association between fecal levels of CgA, CgB, SgII, and SgIII, with the clinical and pathophysiological phenotype of irritable bowel syndrome (IBS) patients.

    METHODS:

    Analyses of CgA, CgB, SgII, SgIII, and calprotectin in fecal samples of 82 IBS patients and 29 healthy controls were performed. All IBS subjects completed validated questionnaires to assess gastrointestinal and psychological symptom severity, and underwent rectal barostat test and colonic transit time measurement.

    RESULTS:

    IBS patients demonstrated higher levels of fecal CgA (P=0.009), SgII (P<0.001), and SgIII (P<0.001), but lower levels of CgB (P<0.001) compared with controls. SgII had good discriminative validity to positively identify IBS patients, with an area under the receiver operating characteristics (ROC) curve (AUROC) of 0.86 (95% confidence interval (CI): 0.78-0.94). SgIII and CgB both had fairly good discriminative validity to positively identify IBS patients, with an AUROC of 0.79 (95% CI: 0.71-0.87) and 0.78 (95% CI: 0.69-0.87), respectively. There were negative correlations between the colonic transit time and fecal levels of CgA (r=-0.53, P<0.001), SgII (r=-0.55, P<0.001), and SgIII (r=-0.28, P=0.03). Perceived abdominal pain was moderately associated with levels of CgA (r=0.32, P=0.004), SgII (r=0.31, P=0.006), and SgIII (r=0.24, P=0.04). Calprotectin levels were not associated with the levels of granins or with the clinical or pathophysiological phenotype of IBS patients.

    CONCLUSIONS:

    Fecal levels of Cg and Sg may be related to the underlying pathophysiology of IBS and of potential importance for symptoms of the patients. Granins also show promise to serve as future biomarkers of IBS. Further studies are needed to explore the potential role of granins in IBS patients.

1234 151 - 179 of 179
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf