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Biomedical subjects

Ora Shovman

Publications and source records attributed to Ora Shovman.

14 recordsLinked to original sources

Lymphocyte resistance to lysophosphatidylcholine mediated apoptosis in atherosclerosis.

OBJECTIVE: Apoptosis is being increasingly regarded as a key component in the development and progression of atherosclerosis. Since it has become apparent that the immune system plays a predominant role in mediating atherogenesis, there has been a growing recognition that the evaluation of lymphocyte apoptosis may contribute to understanding a persistent altered immune and inflammatory response. The aim of the present study was to evaluate the apoptotic effect of lysophosphatidylcholine (LPC) on peripheral blood lymphocytes (PBL) derived from unstable angina (UA) patients, as compared to healthy donors. METHODS: PBL isolated from 27 healthy donors and 25 age matched UA patients were examined. Early apoptotic events induced by LPC in resting and phytohemagglutinin (PHA)-activated lymphocytes were evaluated by several apoptotic assays. The levels of intracellular reactive oxygen species (ROS) and the expression of apoptotic regulated proteins (Bcl-2 and Bax) were measured. RESULTS: LPC was found to induce apoptosis in normal activated lymphocytes, in a dose- and time-dependent manner, in association with an increase in intracellular ROS. In UA patients, an exposure of PHA-activated PBL to LPC triggered neither an increase in ROS generation, nor in the apoptotic manifestations, and was associated with a significantly lower ratio of Bax/Bcl-2 expression. CONCLUSION: Our results indicate that PBL isolated from UA patients may be resistant to apoptosis induction by LPC, resulting from oxidative stress challenge and dysregulation of apoptosis-related protein expression.

Adult↗

Pathogenic role and clinical relevance of antineutrophil cytoplasmic antibodies in vasculitides.

Within the last year, a growing body of evidence for a distinct role of antineutrophil cytoplasmic antibodies (ANCA) in the pathogenesis of ANCA-associated vasculitides (AAV) has developed. An experimental model of myeloperoxidase (MPO)-ANCA-associated vasculitis provided direct and convincing in vivo evidence that MPO-ANCA are primary pathogenic factors in small-vessel vasculitis by augmenting of leukocyte-vessel wall interaction and leukocyte-mediated vascular injury. Determination of bacterial lipopolysaccharide (LPS) effects on disease severity in a mouse model of anti-MPO-induced glomerulonephritis showed that ANCA and other proinflammatory stimuli of infectious origin acted in synergism in the development of destructive inflammation.

Animals↗

An outbreak of Phialemonium infective endocarditis linked to intracavernous penile injections for the treatment of impotence.

BACKGROUND: In March 2002, a patient in Tel Aviv, Israel, died of endocarditis caused by Phialemonium curvatum. As part of his therapy for erectile dysfunction, the patient had been trained to self-inject a compound of vasoactive drugs provided by an impotence clinic into his penile corpus cavernosous. METHODS: We identified the used prefilled syringes as the source of his infection. Similar cases were investigated as a putative outbreak of P. curvatum invasive disease among customers of this impotence clinic. P. curvatum isolates, cultured from samples obtained from the patients and from prefilled syringes, were compared by DNA sequencing of the nuclear ribosomal internal transcribed spacer. RESULTS: We identified 2 additional customers at the impotence clinic who had P. curvatum endocarditis. In addition, cultures of unused, prefilled syringes and bottles provided by the same clinic to 5 asymptomatic customers tested positive for pathogenic molds (P. curvatum in 4 cases and Paecilomyces lilacinus in 1). All P. curvatum isolates were of a single genetic type that is known only from this outbreak but is closely related to 3 other P. curvatum genotypes associated with pathogenicity in humans. CONCLUSIONS: P. curvatum is an emerging pathogen that can be readily isolated from blood. We identified an outbreak of P. curvatum endocarditis among men who had erectile dysfunction treated by intracavernous penile injections from contaminated prefilled syringes.

Aged↗

Statins and autoimmune diseases.

Inhibitors of 3-hydroxy-3methylglytaryl coenzyme A (HMG-CoA) reductase or statins are effective lipid lowering drugs widely used in cardiovascular disease. In the recent years, pleotropic effects of statins have been reported, which include anti-inflammatory and immunomodulatory properties. This review discusses the anti-inflammatory and immunomodulatory roles of statins and their possible use for the treatment of other inflammatory diseases or conditions with the involvement of the immune system.

Animals↗

The homogeneous multiplexed system--a new method for autoantibody profile in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease leading to immunological aberrations and excessive multiple autoantibody production. The aim of this study was to investigate the prevalence of multiple autoantibodies in SLE patients utilizing the multiplex system method. We analyzed the presence of elevated titers of anti-Ro, anti-La, anti-RNP, anti-Sm, anti-Jo1, anti-centromere, anti-Scl-70, anti-histone, and anti-dsDNA antibodies in 199 serum samples (113 SLE patients, 86 healthy donors). We compared the type, level and number of autoantibodies and the correlation between the autoantibody profile and disease severity utilizing the SLEDAI score. Elevated titers of at least one autoantibody were detected in 48% of 42 SLE patients. Elevated titers of anti-Ro antibodies were most commonly detected. The distribution of specific autoantibodies was: anti-Ro- 23.8%, anti-dsDNA- 19%, antihistone- 19%, anti-RNP- 14.2%, anti-La antibodies- 11.9%, anti-Sm- 7.1%, anti-Scl 70-4.7%, and anti-centromere- 2.4%. Utilizing ROC analysis, the sensitivity and specificity of anti-DNA antibodies at a cutoff value of 34 IU/ml were 87.1% and 79.4% respectively. Elevated titers of anti-Jo1 antibody were not detected. There was a correlation with the titer of anti-Ro antibodies and disease activity by the SLEDAI score. Seven patients harbored one autoantibody only, 15 patients harbored 2-3 autoantibodies, 3 patients harbored 4-5 autoantibodies, and one patient harbored 6 autoantibodies. A correlation between the number of autoantibodies per patient and disease severity was found. One patient with a multitude of autoantibodies had severe lupus and a myriad of clinical manifestations. In conclusion, the multiplex system is specific and sensitive, provides an autoantibody profile in a single test, and may be useful as a diagnostic test for SLE. Elevated anti-Ro antibodies are associated with severe disease. An autoantibody load may be indicative of more severe disease.

Antibodies, Antinuclear↗

Low levels of heat shock proteins-60 and -65 autoantibodies in Sjögren's syndrome.

BACKGROUND: Heat shock proteins are highly conserved immunodominant antigens found in various species. Humoral immune responses to mycobacterial HSP65 and human HSP60 have been established in a number of human autoimmune diseases. OBJECTIVE: To assess the prevalence of antibodies to HSP60 kDa and HSP65 kDa in patients with Sjögren's syndrome as compared to normal subjects. METHODS: Thirty-seven patients with SS were compared with normal controls. The antibodies against human HSP60 were measured by the Anti-Human (IgG/IgM) HSP60 ELISA kit. IgGs and IgMs to mycobacterial HSP65 were determined using an enzyme-linked immunosorbent assay with mycobacterial recombinant HSP65 antigens. RESULTS: The levels of both anti-HSP60 and -HSP65 were lower in patients compared with controls. IgG autoantibodies to HSP60 were significantly different between groups: 162 +/- 55.1 ng/ml in controls versus 112.3 +/- 30.6 ng/ml in SS patients (P < 0.001). The levels among controls of anti-HSP65 IgM isotype were also significantly higher than among the SS patients: 111.6 +/- 33.4 U/ml versus 96.1 +/- 8.9 U/ml (P= 0.01). CONCLUSIONS: The results of the present study show that the levels of different isotypes of anti- HSP60 and HSP65 antibodies were lower in patients with SS than in normal subjects. Additional studies in larger patient populations are required to evaluate the prevalence of these autoantibodies in SS patients.

Autoantibodies↗

Pericarditis following permanent pacemaker insertion.

BACKGROUND: The appearance of pericarditis following insertion of a permanent pacemaker is not widely acknowledged in the literature. OBJECTIVES: To describe our experience with pericarditis following 395 permanent pacemaker implantations over 2 years. METHODS: We retrospectively reviewed the medical records of 395 consecutive patients in whom new pacing systems or pacemaker leads had been implanted over a 2 year period. We searched the records for pericarditis that developed within 1 month after pacemaker implantation according to the ICD-9 code. The incidence, clinical picture, response to treatment, and relationship to lead design and location were studied. RESULTS: Eight cases (2%) of pericarditis following implantation were detected. Clinical manifestations in all patients were similar to those of post-pericardiotomy syndrome and included chest pain (n = 7), friction rub (n = 1), fever (n = 2), fatigue (n = 2), pleural effusion (n = 2), new atrial fibrillation (n = 2), elevated erythrocyte sedimentation rate (n = 4), and echcardiographic evidence of pericardial effusion (n = 8). All affected patients had undergone active fixation (screw-in) lead implantation in the atrial position. The incidence of pericarditis with screw-in atrial leads was 3% compared to 0% in other cases (P < 0.05). CONCLUSIONS: Pericarditis is not uncommon following pacemaker implantation with active fixation atrial leads. Special attention should be paid to identifying pericardial complications following pacemaker implantation, especially when anticoagulant therapy is resumed or initiated. The use of passive fixation leads is likely to reduce the incidence of pericarditis but this issue should be further investigated.

Adrenal Cortex Hormones↗

Antiinflammatory and immunomodulatory properties of statins.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase or statins constitute the most powerful class of lipid lowering drugs, widely used in medical practice. During the past several years additional actions of statins unrelated to cholesterol reduction have been identified which includes antiinflammatory and immunomodulatory properties. Since atherosclerosis is a form of inflammation and the immune system play an important role in its pathogenesis, pleiotropic effect of statins may provide complementary explanation to their clinical benefit. This article reviews the data regarding the antiinflammatory and immunomodulatory properties of the statins that are available in the treatment of atherosclerosis and possibly may be applicable in other inflammatory diseases or conditions with the involvement of the immune system.

Animals↗