Major Inhibitor (major + inhibitor)

Distribution by Scientific Domains

Selected Abstracts

Immune-expression of HSP27 and IL-10 in recurrent aphthous ulceration

Nelson T. Miyamoto Jr
Background:, Recently, abnormal cellular immune response has been considered responsible for the oral lesion in the recurrent aphthous ulceration (RAU). For reasons not yet defined, antigens of the oral microbiota would trigger abnormal Th1 immune response against epithelial cells. On the other hand, studies have demonstrated that heat shock proteins (HSP) can block the production of proinflammatory cytokine through inhibition of NF-,B and mitogen-activated protein kinase pathways or activate anti-inflammatory cytokines and therefore control the magnitude of the immune response. HSP27 has been considered a powerful inductor of IL-10, a major inhibitor of Th1 response. Methods:, Using immunohistochemistry, we studied the expression and location of HSP27 and IL-10 in ulcerated lesions clinically diagnosed as RAU (n = 27) and to compare it with that of oral clinically normal mucosa (CT; n = 6) and of other inflammatory chronic diseases such as oral fibrous inflammatory hyperplasia (FIH; n = 18), Crohn's disease (CD; n = 10) and ulcerative colitis (UC; n = 9). Results:, A lower proportion of HSP27-positive epithelial cells in RAU and CD were observed when compared with CT and FIH (P < 0.001**; P = 0.013**). A lower proportion of IL-10-positive interstitial cells in RAU was observed when compared with FIH, UC, CT and CD (P < 0.001**; P < 0.001**; P < 0.001**; P = 0.034*). Conclusion:, Altogether the data suggest that a reduced cellular expression of HSP27 and IL-10 in RAU might be related with the aetiopathogenesis of the ulcerated oral lesions. [source]

Plasma Antithrombin Activity as a Diagnostic and Prognostic Indicator in Dogs: A Retrospective Study of 149 Dogs

S. Kuzi
Background: Antithrombin (AT) is the major inhibitor of coagulation. In people, hypoantithrombinemia is associated with hypercoagulability, thrombosis, and poor prognosis. Veterinary studies, however, have not demonstrated similar prognostic significance. Thus, AT activity (ATA) in dogs currently is interpreted based on human medicine guidelines. Hypothesis: ATA can serve as a prognostic marker in dogs, as has been shown in people. Objectives: (1) To describe the clinical and clinicopathologic findings, diagnoses, and outcome of dogs with decreased versus normal ATA, (2) to identify diseases and mechanisms associated with hypoantithrombinemia, and (3) to assess ATA as a prognostic indicator. Animals and Methods: Retrospective study of 149 dogs with ATA measurement during their disease course. Results: Hypoantithrombinemic dogs had a higher proportion of leukocytosis, hemostatic abnormalities, hypoalbuminemia, and hyperbilirubinemia versus dogs with normal ATA. Hypoantithrombinemia commonly was present in immune-mediated hemolytic anemia (IMHA), pancreatitis, hepatopathy, and neoplasia. It was associated with higher risk of mortality in the entire study population and for specific diseases (eg, IMHA, neoplasia). The odds ratio for mortality significantly and progressively increased when ATA was <60 and <30% (9.9, 14.7, respectively). A receiver operating characteristics analysis of ATA as a predictor of mortality showed an area under the curve of 0.7, and an optimal cutoff point of 60% yielded sensitivity and specificity of 58 and 85%, respectively. Conclusions and Clinical Importance: In dogs, ATA <60% indicates increased mortality risk, similarly to human patients, but ATA has limited value as a single discriminating factor in the outcome. [source]

A-G-4G haplotype of PAI-1 gene polymorphisms ,844 G/A, HindIII G/C, and ,675 4G/5G is associated with increased risk of ischemic stroke caused by small vessel disease

M. G. Adamski
Background,,, Plasminogen activator inhibitor type 1 (PAI-1) is the major inhibitor of fibrinolysis. It was reported that PAI-1 gene polymorphisms affected PAI-1 level and might therefore influence the risk of vascular diseases, including stroke. We studied the association of three common polymorphisms in PAI-1 gene (,844 G/A, ,675 4G/5G, and HindIII G/C) with the odds of different causes of ischemic stroke. Methods,,, We studied 390 patients with ischemic stroke due to large vessel disease (n = 117), small vessel disease (n = 121), and cardioembolism (n = 152) as well as 291 controls. The etiology of ischemic stroke was established using TOAST criteria. PAI-1 polymorphisms were genotyped with restriction fragment length polymorphism and single strand conformation polymorphism method. Results,,, A-G-4G haplotype of PAI-1 gene was found more frequently in stroke patients with small vessel disease than in control subjects (44.9% vs 35.7%; P = 0.02). No association was found between investigated genotype or allele frequencies and distinct causes of ischemic stroke. Conclusions,,, Our results demonstrate that A-G-4G PAI-1 gene haplotype is associated with increased risk of small vessel disease stroke, but this study does not support an association of ,844 G/A, ,675 4G/5G, and HindIII G/C PAI-1 gene polymorphisms with particular etiology of ischemic stroke. [source]

Plasminogen activator inhibitor-1 and asthma: role in the pathogenesis and molecular regulation

Z. Ma
Summary Plasminogen activator inhibitor (PAI)-1 is a major inhibitor of the fibrinolytic system. PAI-1 levels are markedly increased in asthmatic airways, and mast cells (MCs), a pivotal cell type in the pathogenesis of asthma, are one of the main sources of PAI-1 production. Recent studies suggest that PAI-1 may promote the development of asthma by regulating airway remodelling, airway hyperresponsiveness (AHR), and allergic inflammation. The single guanosine nucleotide deletion/insertion polymorphism (4G/5G) at ,675 bp of the PAI-1 gene is the major genetic determinant of PAI-1 expression. Plasma PAI-1 level is higher in people with the 4G/4G genotype than in those with the 5G/5G genotype. A strong association between the 4G/5G polymorphism and the risk and the severity of asthma has been suggested. Levels of plasma IgE and PAI-1 and severity of AHR are greater in asthmatic patients with the 4G/4G genotype than in those with the 5G/5G genotype. The PAI-1 promoter with the 4G allele renders higher transcription activity than the PAI-1 promoter with the 5G allele in stimulated MCs. The molecular mechanism for the 4G allele-mediated higher PAI-1 expression is associated with greater binding of upstream stimulatory factor-1 to the E-box adjacent to the 4G site (E-4G) than to the E-5G. In summary, PAI-1 may play an important role in the pathogenesis of asthma. Further studies evaluating the mechanisms of PAI-1 action and regulation may lead to the development of a novel prognostic factor and therapeutic target for the treatment and prevention of asthma and other PAI-1-associated diseases. [source]