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Biologic Mechanisms (biologic + mechanism)
Selected AbstractsHelicobacter pylori Infection and Iron Stores: A Systematic Review and Meta-analysisHELICOBACTER, Issue 5 2008Khitam Muhsen Abstract Background and Aims:, We carried out a systematic literature review and meta-analysis to evaluate the existing evidence on the association between Helicobacter pylori infection and iron stores. Methods:, Twelve case reports and case series, 19 observational epidemiologic studies and six intervention trials were included in the review. Results:, Although only few studies controlled for multiple potential confounders, most studies reported a positive association, linking between H. pylori and decreased body iron stores in symptomatic and asymptomatic H. pylori -infected subjects. H. pylori infection may be regarded as a risk factor for reduction in body iron stores and also for iron deficiency or iron deficiency anemia, especially in high-risk groups. The results of the meta-analysis of thoroughly designed and analyzed studies revealed an increased risk for iron deficiency anemia; pooled odds ratio (OR) 2.8 (95% confidence interval (CI) 1.9, 4.2) and also for iron deficiency; pooled OR 1.38 (95%CI 1.16,1.65) among H. pylori -infected subjects. The biologic mechanism by which H. pylori induces the alteration in the iron stores is not fully understood, but it seems to involve several pathways, including gastrointestinal blood loss, decrease in the absorption of dietary iron, and enhanced uptake of the iron by the bacterium. Conclusions:,H. pylori is associated with reduced iron stores. Future research is needed to determine whether this relationship is a causal association and to better understand its biologic mechanism. The impact of anti- H. pylori therapy on improvement of iron stores needs to be further evaluated in large and well-controlled trials. [source] Clinical risk factors for portopulmonary hypertension,HEPATOLOGY, Issue 1 2008Steven M. Kawut Portopulmonary hypertension affects up to 6% of patients with advanced liver disease, but the predictors and biologic mechanism for the development of this complication are unknown. We sought to determine the clinical risk factors for portopulmonary hypertension in patients with advanced liver disease. We performed a multicenter case-control study nested within a prospective cohort of patients with portal hypertension recruited from tertiary care centers. Cases had a mean pulmonary artery pressure > 25 mm Hg, pulmonary vascular resistance > 240 dynes · second · cm,5, and pulmonary capillary wedge pressure , 15 mm Hg. Controls had a right ventricular systolic pressure < 40 mm Hg (if estimable) and normal right-sided cardiac morphology by transthoracic echocardiography. The study sample included 34 cases and 141 controls. Female sex was associated with a higher risk of portopulmonary hypertension than male sex (adjusted odds ratio = 2.90, 95% confidence interval 1.20-7.01, P = 0.018). Autoimmune hepatitis was associated with an increased risk (adjusted odds ratio = 4.02, 95% confidence interval 1.14-14.23, P = 0.031), and hepatitis C infection was associated with a decreased risk (adjusted odds ratio = 0.24, 95% confidence interval 0.09-0.65, P = 0.005) of portopulmonary hypertension. The severity of liver disease was not related to the risk of portopulmonary hypertension. Conclusion: Female sex and autoimmune hepatitis were associated with an increased risk of portopulmonary hypertension, whereas hepatitis C infection was associated with a decreased risk in patients with advanced liver disease. Hormonal and immunologic factors may therefore be integral to the development of portopulmonary hypertension. (HEPATOLOGY 2008.) [source] The risk of pancreatic cancer in patients with gastric or duodenal ulcer diseaseINTERNATIONAL JOURNAL OF CANCER, Issue 2 2007Juhua Luo Abstract Although Helicobacter pylori (H. pylori) seropositivity is linked to an excess risk of pancreatic cancer, the biologic mechanism is unknown. Gastric ulcer is primarily associated with corpus colonization of H. pylori, atrophic gastritis and formation of N -nitrosamines. Duodenal ulcer is a marker of antral colonization, hyperacidity and uninhibited secretin release. We estimated relative risks for pancreatic cancer among patients with gastric or duodenal ulcer, based on a register-based retrospective cohort study with 88,338 patients hospitalized for gastric ulcer and 70,516 patients for duodenal ulcer recorded in the Swedish Inpatient Register between 1965 and 2003. Following operation, the 14,887 patients who underwent gastric resection and 8,205 with vagotomy were analyzed separately. Multiple record-linkages allowed complete follow-up and identification of all incident cases of pancreatic cancer until December 31, 2003. Standardized incidence ratios (SIRs) estimated relative risks. During years 3,38 of follow-up, we observed a 20% excess risk (95% confidence interval [CI] 10,40%) for pancreatic cancer among unoperated gastric ulcer patients. The excess increased to 50% (95% CI 10,110%) 15 years after first hospitalization (p for trend = 0.03). SIR was 2.1 (95% CI 1.4,3.1) 20 years after gastric resection. Unoperated duodenal ulcer was not associated with pancreatic cancer risk, nor was vagotomy. Our results lend indirect support to the nitrosamine hypothesis, but not to the hyperacidity hypothesis in the etiology of pancreatic cancer. © 2006 Wiley-Liss, Inc. [source] Biological foundation for periodontitis as a potential risk factor for atherosclerosisJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2005Yong-Hee P. Chun Objectives:, Links between periodontal diseases and systemic diseases have been well documented by epidemiological studies. Recently, research has shifted to elucidating the biologic mechanism for a causal relationship. One focus of interest is atherosclerosis, the underlying event of cardiovascular diseases due to its serious health impact. However, it is still not clear whether periodontopathic pathogens are truly etiologic agents or ubiquitous bystanders. This article reviews the current understanding about the molecular biological interactions between periodontal disease and atherosclerosis and the biological plausibility of periodontitis as a potential risk factor for cardiovascular disease. Materials and methods:, The current literature regarding periodontal diseases and atherosclerosis and coronary vascular disease was searched using the Medline and PubMed databases. Results:,In vitro experiments and animal models are appropriate tools to investigate the biological interactions between periodontal disease and atherosclerosis at the cell molecular level. The concepts linking both pathologies refer to inflammatory response, immune responses, and hemostasis. In particular, Porphyromonas gingivalis appears to have unique, versatile pathogenic properties. Whether or not these findings from isolated cells or animal models are applicable in humans with genetic and environmental variations is yet to be determined. Likewise, the benefit from periodontal therapy on the development of atherosclerosis is unclear. Approaches targeting inflammatory and immune responses of periodontitis and atherosclerosis simultaneously are very intriguing. Conclusion:, An emerging concept suggests that a pathogenic burden from different sources might overcome an individual threshold culminating in clinical sequela. P. gingivalis contributes directly and indirectly to atherosclerosis. [source] Selective cyclooxygenase-2 inhibition suppresses basic fibroblast growth factor expression in human esophageal adenocarcinomaMOLECULAR CARCINOGENESIS, Issue 12 2007Mark Baguma-Nibasheka Abstract Inhibition of cyclooxygenase (COX)-2 is reported to suppress growth and induce apoptosis in human esophageal adenocarcinoma (EADC) cells, although the precise biologic mechanism is unclear. In this study we tested the hypothesis that the antitumor activity of COX-2 inhibitors may involve modulation of basic fibroblast growth factor (FGF-2), which is overexpressed in EADC. We evaluated the effects of NS-398, a selective COX-2 inhibitor, on FGF-2 expression and proliferation of EADC cell lines that express COX-2 and those that do not. We also correlated COX-2 and FGF-2 expression with clinico-pathologic findings and outcome in a well-characterized series of surgically resected EADC tissues. Seg-1 cells robustly expressed COX-2 and FGF-2, whereas Bic-1 cells expressed neither transcript. FGF-2 was reduced to undetectable levels in Seg-1 cells following NS-398 treatment, but increased within 4 h of drug removal. NS-398 significantly inhibited the growth of Seg-1 cells, and this effect was ameliorated by addition of exogenous FGF-2. In contrast, NS-398 had no effect on Bic-1 cell proliferation and FGF-2 alone had no effect on proliferation of either cell line. NS-398, or a neutralizing anti-FGF-2 antibody, induced apoptosis in Seg-1 cells, and these effects were inhibited by addition of exogenous FGF-2. COX-2 protein was strongly expressed in 46% (10/22) of EADCs, and was associated with a trend towards reduced disease-free survival. These findings indicate that the antitumor effects of COX-2 inhibition in EADC cells may be mediated via suppression of FGF-2, and that COX-2 may be a clinically relevant molecular marker in the management of human EADC. © 2007 Wiley-Liss, Inc. [source] An Approach to Interdisciplinary Training in Postgraduate EducationEUROPEAN JOURNAL OF DENTAL EDUCATION, Issue 2 2006P Brodin Aims, A primary goal for clinical graduate training is to provide the student with the expertise required for specialist treatment in the actual discipline. At the same time there is an increasing need for a broader perspective on specialist care and the students should be aware of the limitations inherent in own specialty. In order to plan treatment in the best interest of the patient, and to be prepared to take part in treatments involving other specialties, the students should be exposed to interdisciplinary cooperation throughout the training. An approach to joint academic and clinical training with the purpose of providing graduate students with a broader perspective on specialist care is described and discussed. Material and methods, During their first year graduate students in the 7 different disciplines complete a joint Core Curriculum consisting of 8 different courses to stimulate a scientific approach to their profession and understanding of basic biologic mechanisms. To create a learning environment focusing on the development of interdisciplinary competence, a joint clinic has been established. Teams of students from different disciplines have been organized in order to establish ,partnership' for the treatment of patients with complex problems. The students also take part in the sessions held by a faculty Team of experts for assessment and treatment planning of referred patients with complex problems. Furthermore, faculty members conduct courses and seminars for students from other disciplines and students also participate in selected parts of the regular program in other disciplines. Results, Formal evaluation has so far been conducted for the Core Curriculum. Most students respond that they are satisfied with the courses, and the curriculum has also been adjusted based on the comments. The students report that treatment of patients in need of interdisciplinary treatment has been facilitated by having ,partners' in other disciplines. Participation in the Team of expert's sessions has been appreciated, and the attendance at interdisciplinary courses and seminars has been good. Conclusions, Based on the experience over the last 5 years, the interdisciplinary aspects of graduate training should be expanded to stimulate a holistic approach also to specialist treatment. [source] Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriersINTERNATIONAL JOURNAL OF CANCER, Issue 1 2006André Nkondjock Abstract Although there are several plausible biologic mechanisms whereby coffee consumption might influence the risk of breast cancer, epidemiologic evidence is limited. We assessed the association between coffee consumption and breast cancer risk among high-risk women who carry BRCA mutations. We performed a matched case-control analysis on 1,690 women with a BRCA1 or BRCA2 mutation from 40 centers in 4 countries. Average lifetime coffee consumption was estimated via a self-administered questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for potential confounders, the ORs for breast cancer in BRCA carriers who habitually drank 0, 1,3, 4,5 and 6 or more cups of coffee were 1.00, 0.90 (95% CI 0.72,1.12), 0.75 (95% CI 0.47,1.19) and 0.31 (95% CI 0.13,0.71; p -trend = 0.02). The effect was limited to the consumption of caffeinated coffee. These results suggest that among women with BRCA gene mutation, coffee consumption is unlikely to be harmful and that high levels of consumption may in fact be related to reduced breast cancer risk. © 2005 Wiley-Liss, Inc. [source] Exclusive Breast-feeding: Does It Have the Potential to Reduce Breast-feeding Transmission of HIV-1?NUTRITION REVIEWS, Issue 11 2000Melanie M. Smith M.N.S. Exclusive breast-feeding is unambiguously the optimal infant feeding practice and is universally promoted in the absence of human immunodeficiency virus (HIV-1). It is associated with reduced morbidity and mortality from diarrheal and respiratory diseases. Recent findings suggest that exclusive breast-feeding may pose less risk of HIV-1 transmission than the more common practice of mixed feeding (i.e., breast-feeding concurreptwith the feeding of water, other fluids, and foods), which has important infant feeding policy implications for low-resource settings. This paper reviews the biologic mechanisms associated with exclusive breast-feeding that provide protection against gastrointestinal, respiratory, and atopic diseases, and evaluates the relevance of these mechanisms for HIV-1 transmission. Potential mechanisms include reduction in dietary antigens and enteric pathogens that may maintain integrity of the intestinal mucosal barrier and limit inflammatory responses of the gut mucosa; promotion of beneficial intestinal microflora that may increase resistance to infection and modulate the infant's immune response; alteration in specific antiviral or anti-inflammatory factors in human milk that may modulate maternal hormonal or immunologic status; and maintenance of mammary epithelial integrity that may reduce viral load in breast milk. [source] Analysis of maternal,offspring HLA compatibility, parent-of-origin effects, and noninherited maternal antigen effects for HLA,DRB1 in systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 6 2010Paola G. Bronson Objective Genetic susceptibility to systemic lupus erythematosus (SLE) is well established, with the HLA class II DRB1 and DQB1 loci demonstrating the strongest association. However, HLA may also influence SLE through novel biologic mechanisms in addition to genetic transmission of risk alleles. Evidence for increased maternal,offspring HLA class II compatibility in SLE and differences in maternal versus paternal transmission rates (parent-of-origin effects) and nontransmission rates (noninherited maternal antigen [NIMA] effects) in other autoimmune diseases have been reported. Thus, we investigated maternal,offspring HLA compatibility, parent-of-origin effects, and NIMA effects at DRB1 in SLE. Methods The cohort comprised 707 SLE families and 188 independent healthy maternal,offspring pairs (total of 2,497 individuals). Family-based association tests were conducted to compare transmitted versus nontransmitted alleles (transmission disequilibrium test) and both maternally versus paternally transmitted (parent-of-origin) and nontransmitted alleles (using the chi-square test of heterogeneity). Analyses were stratified according to the sex of the offspring. Maternally affected offspring DRB1 compatibility in SLE families was compared with paternally affected offspring compatibility and with independent control maternal,offspring pairs (using Fisher's test) and was restricted to male and nulligravid female offspring with SLE. Results As expected, DRB1 was associated with SLE (P < 1 × 10,4). However, mothers of children with SLE had similar transmission and nontransmission frequencies for DRB1 alleles when compared with fathers, including those for the known SLE risk alleles HLA,DRB1*0301, *1501, and *0801. No association between maternal,offspring compatibility and SLE was observed. Conclusion Maternal,offspring HLA compatibility, parent-of-origin effects, and NIMA effects at DRB1 are unlikely to play a role in SLE. [source] Liver X receptor agonism promotes articular inflammation in murine collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 9 2009Darren L. Asquith Objective Liver X receptors (LXRs) have previously been implicated in the regulation of inflammation and have, in general, been ascribed an antiinflammatory role. This study was therefore undertaken to explore the biologic mechanisms of LXRs in vivo and in vitro in an experimental inflammatory arthritis model. Methods Male DBA/1 mice were immunized with type II collagen and treated from an early or established stage of arthritis with 2 different concentrations of the LXR agonists T1317 and GW3965 or vehicle control. The mice were monitored for articular inflammation and cartilage degradation by scoring for clinical signs of arthritis, histologic examination of the joints, and analysis of serum cytokine and antibody levels. In vitro, primary human monocytes and T cells were cultured in the presence of GW3965 or T1317, and the concentrations of proinflammatory cytokines were measured by multiplex assay. Results Contrary to expectations, LXR agonism with the use of 2 discrete, specific molecular entities led to substantial exacerbation of articular inflammation and cartilage destruction in this murine collagen-induced arthritis model. This was associated ex vivo with elevated cytokine expression, with enhanced Th1 and Th17 cellular responses, and with elevated collagen-specific autoantibody production. In vitro, LXR agonists, in concert with lipopolysaccharide, promoted cytokine and chemokine release from human monocytes, and similar effects were observed in a T cell,macrophage coculture model that closely recapitulates the pathways that drive synovial cytokine release. Conclusion Since LXRs are present in rheumatoid arthritis (RA) synovium, these results suggest that LXR-mediated pathways could exacerbate the chronic inflammatory response typical of RA. [source] Clinical responses to tumor necrosis factor , antagonists do not show a bimodal distribution: Data from the Stockholm Tumor Necrosis Factor , Followup RegistryARTHRITIS & RHEUMATISM, Issue 6 2003Ronald F. van Vollenhoven Objective To study the distribution of clinical responses to treatment with the tumor necrosis factor , (TNF,) antagonists etanercept and infliximab, and in particular, to determine whether there is a biologically meaningful distinction between responders and nonresponders. Methods Among patients in the Stockholm TNF, Followup Registry, we analyzed the clinical responses to etanercept and infliximab, using the American College of Rheumatology (ACR) core set of outcome measures. For each parameter, the absolute change (value at baseline , current value) and the percentage change ([absolute change]/[value at baseline] × 100) from baseline were calculated. The results were plotted as histograms and inspected visually, and the distributions were statistically compared with computer-generated normal distributions. Results Absolute and relative changes in outcomes on the ACR core set of measures in 406 patients receiving etanercept or infliximab were studied. All but a few of these analyses yielded normal or somewhat skewed distributions. The statistical analyses did not detect any non-normal distributions, and visually, the distributions did not appear to be bimodal. Conclusion The clinical response to TNF, blockade displays a normal or skewed, but not bimodal, distribution. The frequently encountered perception that a clear distinction can be made between responders and nonresponders is not borne out. These relatively straightforward findings imply that the biologic mechanisms determining responsiveness to TNF, blockade are multifactorial and may also have important implications for regulatory guidelines pertaining to treatment with these biologic agents. [source] | ||||||||||