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M Blank

Publications and source records attributed to M Blank.

317 records · Page 18Linked to original sources
PubMedDate not supplied

Livedo reticularis is a marker for predicting multi-system thrombosis in antiphospholipid syndrome.

OBJECTIVE: Livedo reticularis (LR) is a skin vasculopathy that has been frequently described in patients with anti-phospholipid syndrome (APS) and reported to be present in association with valvular heart pathology and strokes (i.e. Sneddon's syndrome). METHODS: In a cohort of APS patients we investigated the possible association of LR with various clinical aspects of APS such as pregnancy morbidity, central nervous system (CNS) and cardiac manifestations. RESULTS: Livedo reticularis was found in 50/308 (16%) of APS patients, and there was a significant association with cerebrovascular accidents (CVA), migraines and epilepsy (p = 0.01, 0.002, and 0.02 respectively). A similar association was also detected between LR, and the presence of cardiac valve thickening and vegetations (p = 0.001). No association with venous thrombosis, recurrent fetal loss, IUGR or toxemia was found. CONCLUSION: Livedo reticularis is a frequent cutaneous manifestation in patients with APS. Its high association with cardiac and CNS thrombosis may suggest that LR-APS patients compose a subset at higher risk for thrombosis, and thus may require a closer follow-up and a more aggressive anticoagulation.

Adult↗
PubMedDate not supplied

New insights into the autoantibody-mediated mechanisms of autoimmune bullous diseases and urticaria.

The skin is a common target of cellular and/or antibody mediated pathological immune responses. Pemphigoids, pemphigus vulgaris and dermatitis herpetiformis are bullous disease due to autoantibodies targeting specific proteins of the skin. The pemphigoid autoantigens are the BP180 and the BP230 antigens, two components of the epithelial basement membrane zone. Additional antigenic targets reported in a portion of patients are laminin 5, the alpha6 subunit of the hemidesmosomal integrin alpha6beta4 and a glycoprotein termed p200. The epidermal and mucosal epithelial cells detachment (acantholysis) characteristic of pemphigus vulgaris is induced by autoantibodies directed against the desmoglein 3 and 1. The desmogleins are desmosomal cadherins, which play a major role in the cell-to-cell adhesion. Dermatitis herpetiformis is regarded as cutaneous phenotype of coeliac disease. A novel autoimmune hypothesis of coeliac disease links wheat gliadin and tissue transglutaminase (TG2) in the gut, which leads to T cell response and IgA autoantibody formation. In dermatitis herpetiformis skin the target for IgA deposition seems to be epidermal TG3. Urticaria is a complex syndrome caused by both immune and non-immune mechanisms. In a subsets of patients with chronic urticaria mast cell degranulation is induced by autoantibodies directed against the a-subunit of the high-affinity IgE receptor, and/or the IgE.

Autoantibodies↗
PubMedDate not supplied

Restricted specificity of anti-ribosomal P antibodies to SLE patients in Israel.

OBJECTIVE: Anti-ribosomal P antibodies (aRib-P Ab) are highly specific for systemic lupus erythematosus (SLE), but their correlatation with disease activity and manifestations including renal, hepatic and central nervous system (CNS) involvement is still controversial. The aim of our study was to evaluate the prevalence of aRib-P Ab and their correlation with clinical manifestations and anti-dsDNA antibodies in SLE patients from Israel. METHODS: Elevated titers of aRib-P Ab utilizing the ELISA method were analyzed in 141 sera samples from 44 SLE patients, 20 Familial Mediterranean Fever (FMF) patients, 22 primary antiphospholipid syndrome (PAPS) patients, 12 patients with infections, and 43 healthy individuals. The SLEDAI score was utilized for assessing SLE disease activity. RESULTS: Elevated titers of aRib-P Ab were present in 11% of SLE patients (n = 6). The mean SLEDAI was 7 (range: 3-10). No statistically significant association was observed between the presence of aRib-P Ab and disease manifestations present in the SLEDAI. The 6 SLE patients had renal disease (n = 1), leucopenia (n = 1), rash (n = 3), and CNS involvement manifested as psychosis (n = 1) or depression (n = 1). Elevated titers of anti-dsDNA antibodies were found in 50% of patients with elevated titers of aRib- P Ab. Patients with PAPS, FMF, infections or healthy controls did not harbor elevated titers of aRib-P Ab. CONCLUSION: Elevated titers of aRib-P Ab were restricted to SLE patients. We confirm previously reported associations of aRib-P Ab reactivity with disease activity and elevated anti-dsDNA Ab titers. No significant correlation with a specific manifestation described on the SLEDAI score was established in this small cohort of patients.

Adolescent↗
PubMedDate not supplied

D-penicillamine-induced autoantibodies in a mouse model.

OBJECTIVE: We have previously shown that the administration of D-penicillamine (D-PEN) to patients with rheumatoid arthritis induces circulating insulin autoantibodies (INSAAB). In order to gain further insight into such immune responses, we measured a battery of circulating autoantibodies in 4 strains of mice receiving D-PEN: C57BL/KsJ, BALB/c, C3H/HeJ, and C57BL/6. These rodents groups differ in their degree of susceptibility to streptozotocin (STZ)-induced immune diabetes (SIMD), which is high in the first 2 strains, and mild and nil in the third and fourth, respectively. METHODS: Randomly assigned animals from each group were given a weekly subcutaneous (SC) injection of either D-PEN 1 mg, D-PEN 3 mg, or solvent (PBS) for a period of 4 weeks. Serum levels of antibodies to insulin, single stranded DNA (ssDNA), thyroglobulin, and cardiolipin were measured weekly. RESULTS: Only the C57BL/KsJ and C3H/HeJ mice reacted to D-PEN administration. When compared to the pre-treated and solvent-treated mice, D-PEN 1 mg, and to a lesser degree D-PEN 3 mg, induced elevation of antibodies to insulin and to ssDNA in C57/KsJ mice (p < 0.001), while only ssDNA antibodies were detected in the C3H/HeJ mice (p < 0.0001 for D-PEN 1 mg; p < 0.05 for D-PEN 3 mg). D-PEN had no effect on the level of antibodies to cardiolipin or to thyroglobulin in any of the mice. CONCLUSIONS: This study showed that D-PEN induces an antigen(s)-specific humoral response only in mice already inherently prone to autoimmunity. This model suggests that the activation of autoimmunity by environmental factors is probably facilitated by genetic background, and might partly explain the diversity of autoimmune manifestations in D-PEN-treated patients.

Animals↗
PubMedDate not supplied

Circasemiseptan (about-half-weekly) and/or circaseptan (about-weekly) pattern in human mitotic activity?

This review and metachronanalysis was prompted by the presence of a circasemiseptan pattern (P < 0.05) found by population-mean cosinor in published data characterizing murine malignant growth after treatment with cyclophosphamide (1-4). For cancer chronotherapy (5-9), the analyses serve to suggest the desirability to extend the focus beyond circadian aspects of drug timing and drug effect to a broader view that takes into account as much of the body's make-up in time as is practical. Among the different components of a chronome (the time structure of rhythms with different frequencies and trends in a given variable), the 3.5-day patterns (circasemiseptans) and the 7-day patterns (circaseptans) are more readily accessible to measurement and thus to manipulation and optimization than infradians with even lower frequencies; they may also be pertinent to the scheduling of infusions covering several days, particularly those using drug administration devices, some of which are programmable. Should circaseptans and circasemiseptans characterize the host as well as the tumor, the drug administration schedule could be optimized for both treatment efficacy and host tolerance, with a view of infradian as well as of circadian and ultradian rhythms.

Chronobiology Phenomena↗
PubMedDate not supplied

Superantigens and experimental SLE induced by idiotypic dysregulation.

OBJECTIVE: The effects of the superantigens (SAgs) Staphylococcal Enterotoxin B (SEB), Toxic Shock Syndrome Toxin-1 (TSST-1) and Mycoplasma Arthritidis Mitogen (MAM) were examined on the induction and on the course of experimental SLE-like disease. METHODS: Immunization of BALB/c mice with human anti-DNA mAb (MIV-7) carrying the pathogenic idiotype 16/6 emulsified in complete Freund's adjuvant (CFA), followed by a boost of MIV-7/PBS 3 weeks later, generated an experimental SLE via an idiotypic dysregulation. RESULTS: After immunization with MIV-7/SAg, replacing the MIV-7 boost by SAg, and then injecting SAg 7 weeks after the regular induction of the SLE-like disease, the mice failed to produce anti-hIgM and dsDNA Ab up to 6 months after the induction. The mice immunized with MIV-7/CFA and boosted with the SAg had high titers of anti-hIgM but no detectable anti-dsDNA Ab. In both experimental groups low titers of anti-CL Abs developed in 25/40 (62%) and 30/38 (79%) of the mice respectively, including the control mice immunized with non-pathogenic human IgM/SAg or PBS/SAg. The mice immunized according to the "classical" protocol showed increased titers of anti-dsDNA Ab (22%) and anti-CL Ab (28%) during 10 weeks of observation. In contrast SEB, TSST-1 and MAM induced a 29%, 1% and 17% reduction in the anti-DNA titers and a 32%, 15% and 12% reduction in the anti-CL titers, respectively. CONCLUSIONS: These data suggest that the SAg tested here cannot replace the effect of CFA in the induction of the primary humoral response. The SAgs TSST-1, SEB and MAM did not induce the SLE-like disease following idiotypic modulation. Moreover, they may have had a suppressive effect on the idiotypic network in our model. The appearance of anti-CL Abs in almost all the experimental groups including the naive mice supports the possibility that microbial SAgs can induce the production of autoantibodies by different mechanisms. The SAgs TSST-1, SEB and MAM reduced autoantibody production in the serologically established idiotypic-induced experimental SLE-like murine model. This beneficial effect may indicate new directions for research on the management of SLE.

Animals↗