| 1. |
- Adamsson, Jenni, 1977, et al.
(author)
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Immune Responses Against Helicobacter pylori in Gastric Cancer Patients and in Risk Groups for Gastric Cancer.
- 2013
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In: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 18:1, s. 73-82
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Journal article (peer-reviewed)abstract
- BACKGROUND: It has previously been reported that weak serum IgG but elevated IgA antibody responses against H.pylori may be associated with risk of gastric cancer (GC) development. To search for potential immunologic markers for GC, we analyzed antibody responses against H.pylori in risk groups of cancer development. MATERIAL AND METHODS: Sera and stomach biopsies collected from H.pylori-infected GC patients as well as from patients with gastric ulcer (GU), atrophic gastritis, intestinal metaplasia (IM) and duodenal ulcer and from H.pylori-infected control subjects without atrophy or IM, and in addition from H.pylori-negative subjects were analyzed for IgG and IgA antibodies against three different H.pylori antigen preparations, that is, membrane protein (MP), urease, and CagA. RESULTS: We observed an increased serum IgA/IgG titer ratio against H.pylori anti-MP in GC and GU patients, and against CagA in Hp-infected GC patients and risk groups. Female patients with GC had a higher serum anti-MP IgA/IgG titer ratio and a higher proportion of poorly differentiated cancer compared with male patients. As earlier observed, the non-tumorous mucosa of H.pylori-infected GC patients contained considerably lower levels of total IgA and H.pylori-specific IgA compared with H.pylori-infected controls. Similarly, we observed decreased specific mucosal anti-MP IgA response in patients with IM. CONCLUSION: We observed several differences in local and systemic immunologic responses against H.pylori in H.pylori-infected GC patients and putative GC risk group patients compared with H.pylori-infected controls. These findings may be of importance in efforts to identify risk groups of GC or early stages of GC.
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| 2. |
- Adrian, Gabriel, et al.
(author)
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Primary tumor volume and prognosis for patients with p16-positive and p16-negative oropharyngeal squamous cell carcinoma treated with radiation therapy
- 2022
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In: Radiation Oncology. - : Springer Nature. - 1748-717X. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The prescribed radiation dose to patients with oropharyngeal squamous cell carcinoma (OPSCC) is standardized, even if the prognosis for individual patients may differ. Easy-at-hand pre-treatment risk stratification methods are valuable to individualize therapy. In the current study we assessed the prognostic impact of primary tumor volume for p16-positive and p16-negative tumors and in relationship to other prognostic factors for outcome in patients with OPSCC treated with primary radiation therapy (RT). Methods: Five hundred twenty-three OPSCC patients with p16-status treated with primary RT (68.0 Gy to 73.1 Gy in 7 weeks, or 68.0 Gy in 4.5 weeks), with or without concurrent chemotherapy, within three prospective trials were included in the study. Local failure (LF), progression free survival (PFS) and overall survival (OS) in relationship to the size of the primary gross tumor volume (GTV-T) and other prognostic factors were investigated. Efficiency of intensified RT (RT with total dose 73.1 Gy or given within 4.5 weeks) was analyzed in relationship to tumor volume. Results: The volume of GTV-T and p16-status were found to be the strongest prognostic markers for LF, PFS and OS. For p16-positive tumors, an increase in tumor volume had a significantly higher negative prognostic impact compared with p16-negative tumors. Within a T-classification, patients with a smaller tumor, compared with a larger tumor, had a better prognosis. The importance of tumor volume remained after adjusting for nodal status, age, performance status, smoking status, sex, and hemoglobin-level. The adjusted hazard ratio for OS per cm3 increase in tumor volume was 2.3% (95% CI 0–4.9) for p16-positive and 1.3% (95% 0.3–2.2) for p16-negative. Exploratory analyses suggested that intensified RT could mitigate the negative impact of a large tumor volume. Conclusions: Outcome for patients with OPSCC treated with RT is largely determined by tumor volume, even when adjusting for other established prognostic factors. Tumor volume is significantly more influential for patients with p16-positive tumors. Patients with large tumor volumes might benefit by intensified RT to improve survival.
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| 3. |
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| 4. |
- Bajor, Antal, 1962, et al.
(author)
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Indirect evidence for increased mechanosensitivity of jejunal secretomotor neurones in patients with idiopathic bile acid malabsorption.
- 2009
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In: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 197:2, s. 129-37
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Journal article (peer-reviewed)abstract
- The interdigestive motor rhythm, the migrating motor complex (MMC), is accompanied by active secretion of chloride during periods of distally propagating maximal motor activity (MMC phase III). We studied the behaviour of this system in bile acid malabsorption (BAM), a relative common cause of chronic diarrhoea. We measured motor activity and transmucosal potential difference (PD, reflecting active chloride secretion), in the proximal jejunum in healthy controls (n = 18) and in a group of patients with BAM (n = 11). The phase III-generated voltage was related to the degree of BAM quantified by the (75)SeHCAT test.
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| 5. |
- Bajor, Antal, 1962, et al.
(author)
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Normal or increased bile acid uptake in isolated mucosa from patients with bile acid malabsorption.
- 2006
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In: Eur J Gastroenterol Hepatol. - 0954-691X. ; 18:4, s. 397-403
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Journal article (peer-reviewed)abstract
- Introduction: Bile acid malabsorption as reflected by an abnormal 75Se-labelled homocholic acid-taurine (75SeHCAT) test is associated with diarrhoea, but the mechanisms and cause-and-effect relations are unclear. Objectives: Primarily, to determine whether there is a reduced active bile acid uptake in the terminal ileum in patients with bile acid malabsorption. Secondarily, to study the linkage between bile acid malabsorption and hepatic bile acid synthesis. Methods: Ileal biopsies were taken from patients with diarrhoea and from controls with normal bowel habits. Maximal active bile acid uptake was assessed in ileal biopsies using a previously validated technique based on uptake of 14C-labelled taurocholate. To monitor the hepatic synthesis, 7[alpha]-hydroxy-4-cholesten-3-one, a bile acid precursor, was assayed in blood. The 75SeHCAT-retention test was used to diagnose bile acid malabsorption. Results: The taurocholate uptake in specimens from diarrhoea patients was higher compared with the controls [median, 7.7 (n=53) vs 6.1 [mu]mol/g per min (n=17)] (P<0.01) but no difference was seen between those with bile acid malabsorption (n=18) versus diarrhoea with a normal 75SeHCAT test (n=23). The 75SeHCAT values and 7[alpha]-hydroxy-4-cholesten-3-one were inversely correlated. Conclusions: The data do not support bile acid malabsorption being due to a reduced active bile acid uptake capacity in the terminal ileum. (C) 2006 Lippincott Williams & Wilkins, Inc.
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| 6. |
- Bajor, Antal, 1962, et al.
(author)
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The bile acid turnover rate assessed with the (75)SeHCAT test is stable in chronic diarrhoea but slightly decreased in healthy subjects after a long period of time.
- 2008
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In: Digestive diseases and sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 53:11, s. 2935-40
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Journal article (peer-reviewed)abstract
- The stability of bile acid turnover rate was evaluated retrospectively using repeat SeHCAT tests in patients with chronic diarrhoea and prospectively for 16 years in healthy subjects. The SeHCAT values were stable in 39 patients with chronic diarrhoea, as shown by a comparison of the test results [data presented as median and (25th-75th percentile)]: 18% (8-23) in the first test versus 14% (9-21) in the second test [n = 39, P = 0.37, time interval 44 months (16-68), repeatability index >95%]. In contrast, they were reduced after 16 years in healthy subjects: 38% (30-49.5) in the first test versus 31% (21-49.5) in the second test (P < 0.03). In healthy subjects, the body mass index increased by 13% from 23.2 kg/m(2) (21-24.6) to 26.2 kg/m(2) (22.5-27.8) (P < 0.01) during the 16 years. There was a negative correlation between hepatic bile acid synthesis and the SeHCAT values (r = -0.615, P = 0.02, n = 14). In conclusion, the turnover rate of bile acids is stable over a long period of time in patients with chronic diarrhoea irrespective of bile acid malabsorption, suggesting that a repeat SeHCAT test is dispensable. There is a significant negative correlation between bile acid synthesis and SeHCAT test results in healthy subjects. The SeHCAT test values are slightly reduced in healthy subjects after 16 years.
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| 7. |
- Bergh, Christina, 1953, et al.
(author)
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Regionalt HTA-arbete kan ge bra genomslag i vården. Goda exempel från Västra Götaland : [Regional HTA work can have a good impact on health care. Good examples form Vastra Gotaland].
- 2010
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In: Läkartidningen. - 0023-7205. ; 107:29-31, s. 1780-1783
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Journal article (peer-reviewed)abstract
- HTA (health technology assessment) innebär en systematisk granskning av det vetenskapliga underlaget för en viss teknik. Ett väl definierat PICO (patients, intervention, comparison, outcome) är en grundförutsättning för att få fram den dokumentation som ska granskas. En fokuserad fråga är central i HTA-processen. En teknik granskas med avseende på effektivitet och risker, etiska och organisatoriska aspekter samt kostnader. I en systematisk litteraturöversikt granskas vetenskapliga artiklar med avseende på kvalitet och relevans. Slutsatserna evidensgraderas enligt GRADE. I Västra Götalandsregionen har inrättats ett HTA-centrum som arbetar med regional medicinsk utvärdering. Regionalt HTA-arbete har flera fördelar; en är att den praktiska omsättningen av de nyvunna kunskaperna troligen kan ske snabbare.
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| 8. |
- Bornstein, JC, et al.
(author)
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Enteric Neural Regulation of Mucosal Secretion
- 2012
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In: Physiology of the Gastrointestinal Tract. 5th Edition. Volume 1. - London : Elsevier. - 9780123820266 ; , s. 769-791
-
Book chapter (peer-reviewed)abstract
- Transport of water and salt across the intestinal mucosa is a major function of the gastrointestinal tract and is regulated by the enteric nervous system. The details of this regulation vary between intestinal regions and between species. However, there are many common elements including that the major output neurons of the secretomotor pathways contain vasoactive intestinal peptide and are located in the submucosal plexus and that there are secretomotor circuits in both the myenteric and submucosal plexuses. These circuits are not simple feed-forward pathways, but include recurrent excitatory networks of intrinsic sensory neurons in both myenteric and submucosal plexuses. These neurons are excited by many sensory stimuli including major nutrients acting via mucosal enteroendocrine cells, and their excitability is enhanced in various diarrheal diseases, which often show disturbed coupling between secretion and motility, suggesting a central role for these circuits.
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| 9. |
- Brynjólfsson, Siggeir Fannar, et al.
(author)
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An Antibody Against Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Dampens Proinflammatory Cytokine Secretion by Lamina Propria Cells from Patients with IBD.
- 2016
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In: Inflammatory bowel diseases. - 1536-4844. ; 22:8, s. 1803-11
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Journal article (peer-reviewed)abstract
- Triggering receptor expressed on myeloid cells 1 (TREM-1) is a potent amplifier of inflammation. Recently, the antimicrobial peptide PGLYRP-1 was shown to be the ligand of TREM-1. Here, the ability of an anti-TREM-1 antibody to dampen the release of proinflammatory cytokines by colon lamina propria cells (LPCs) from patients with IBD was investigated and correlated with PGLYRP-1 levels.Biopsies from patients with ulcerative colitis (UC, n = 45) or Crohn's disease (CD, n = 26) were compared with those from individuals undergoing colonoscopy for other reasons (n = 17). TREM-1 expression was analyzed on myeloid cells by flow cytometry. Cell culture experiments with LPCs were used to analyze PGLYRP-1 and inflammatory cytokine levels and assess the effect of anti-TREM-1 on cytokine secretion.The frequency of TREM-1-expressing neutrophils and recruited macrophages was higher in inflamed than in noninflamed biopsies. The PGLYRP-1 level in inflamed tissue was higher than in noninflamed tissue; it was produced primarily by neutrophils, and its level correlated with the secretion of proinflammatory cytokines. Secretion of myeloperoxidase, tumor necrosis factor-α, interleukin-1β, and interleukin-8 by LPCs stimulated with the potent TREM-1 agonist consisting of PGLYRP-1 complexed with peptidoglycan was reduced in the presence of anti-TREM-1. Moreover, a blocking effect of anti-TREM-1 was apparent when LPCs from a subset of inflamed individuals with elevated PGLYRP-1 were stimulated with killed bacteria.An anti-TREM-1 antibody can dampen secretion of proinflammatory cytokines in inflamed patients with elevated PGLYRP-1. Moreover, PGLYRP-1 + myeloperoxidase is a potential biomarker for predicting the effect of anti-TREM-1 therapy.
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| 10. |
- Dahlén, Rahil, et al.
(author)
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Infliximab Inhibits Activation and Effector Functions of Peripheral Blood T Cells in vitro from Patients with Clinically Active Ulcerative Colitis
- 2013
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475. ; 78:3, s. 275-284
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Journal article (peer-reviewed)abstract
- Many patients with inflammatory bowel disease (IBD) are undergoing therapy with infliximab, an antibody specific for TNF. However, the exact mechanisms of action of infliximab are not completely understood. The aim of this study was to determine the in vitro effects of infliximab on blood T cells derived from anti-TNF therapy-naive ulcerative colitis (UC) patients with clinically active disease. Peripheral blood mononuclear cells were stimulated polyclonally or by antigen in the presence or absence of infliximab. The T cell phenotype was investigated by flow cytometry, cytokine secretion was determined by ELISA, and cell proliferation was determined by thymidine assay or CFSE dye. Presence of infliximab resulted in reduced expression of CD25 in CD4(+) and CD8(+) T cell populations and inhibited secretion of IFN-, IL-13, IL-17A, TNF as well as granzyme A. Infliximab also suppressed CD4(+) and CD8(+) T cell proliferation. These effects of infliximab were recorded both in T cells activated by polyclonal and antigen-specific stimulation. The effects of infliximab on T cell apoptosis and induction of FOXP3(+)CD4(+) T regulatory cells were ambiguous and depended on the originating cellular source and/or the stimulation mode and strength. In conclusion, infliximab is able to reduce T cell activation as measured by CD25, proliferation and cytokine secretion in vitro from UC patients with clinically active disease. These data suggest that suppression of T cell activity may be important for infliximab-mediated disease remission in patients with UC.
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