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Biomedical subjects

Z M Sthoeger

Publications and source records attributed to Z M Sthoeger.

At least 37 records · Page 2Linked to original sources
PubMed1996

Palmar fasciitis and polyarthritis associated with ovarian carcinoma in a young patient. A case report and review of the literature.

Palmar fasciitis and polyarthritis (PFPA) is an uncommon syndrome characterized by progressive and extensive rheumatic disease. It has usually been associated with neoplasms, most commonly in elderly patients, preceding or accompanying the diagnosis of malignancy. We report a case of a 25-year-old patient with severe deforming PFPA preceding the diagnosis of carcinoma of the ovary. The histopathological findings of diffuse fibrosis, connective tissue proliferation and vasculitis with C3 and IgM deposits in subcutaneous tissue and synovia may further clarify the possible pathogenesis of this unique syndrome.

Adult↗
PubMed1996

Anticardiolipin, but not the 16/6 Id anti-DNA antibody induces pregnancy failure.

The primary antiphospholipid syndrome or the antiphospholipid syndrome in systemic lupus erythematosus patients (defined as secondary antiphospholipid syndrome) are characterized by the presence of thrombosis, thrombocytopenia and recurrent fetal loss in association with anticardiolipin antibodies. To determine the causal role of these antibodies in the pathogenesis of pregnancy failure we studied the effects of immunization with monoclonal anti-DNA antibody (designated 16/6 Id; no cardiolipin reactivity) and anticardiolipin monoclonal antibody (designated 2C4C2; binds DNA as well) on the outcome of allogeneic pregnancies in BALB/c mice. Mating of BALB/c females 4 weeks after active immunization with the 16/6 Id, anti-DNA monoclonal antibody resulted in normal pregnancy outcome, similar to control mouse groups. In contrast to that, immunization with the 2C4C2 anticardiolipin antibodies resulted in severe gestational failure with low pregnancy rate, low numbers of fetuses and high rates of resorptions. The fertility index of those mice was extremely low as compared to the 16/6 Id-immunized mice or the control groups. Furthermore, a correlation was shown between the presence of anticardiolipin antibody levels in the sera of the mice at the time of gestation and the pregnancy fate. The 2C4C2-immunized mice which produced high levels of anticardiolipin antibodies demonstrated severe pregnancy failure, whereas normal gestations were observed in the 16/6 Id primed or the control mouse groups that did not produce measurable amounts of the latter antibodies. Thus, our studies demonstrate that anticardiolipin but not the 16/6 Id anti-DNA antibodies can induce severe gestational impairment.

Abortion, Spontaneous↗
PubMed1996

Polymyositis, arthritis, and proteinuria in a patient with adult celiac disease.

A 37-year-old woman developed polymyositis and arthritis concomitantly with proteinuria and watery diarrhea. Repeated duodenal biopsies and serological evaluation established the diagnosis of adult celiac disease. Treatment with gluten-free diet resolved all clinical and laboratory abnormalities. We believe that this is the first report of adult celiac disease presenting as a multisystem disease involving kidneys, joint, and muscles.

Adult↗
PubMed1994

IgG+, CD5+ human chronic lymphocytic leukemia B cells. Production of IgG antibodies that exhibit diminished autoreactivity and IgG subclass skewing.

Several questions exist regarding CD5+ B cells. These include the ability of these cells, as compared to CD5- B cells, to undergo an Ig isotype class switch, the subclasses utilized, and the effects that switching may have on antigen binding. To address these issues, ten patients with chronic lymphocytic leukemia (CLL) whose CD5+ leukemic B cell clones produced IgG were studied. Monoclonal IgG was collected from PMA-stimulated CLL cells and from heterohybridomas constructed with these cells, and then analyzed for IgG subclass utilization, autoreactivity, and DNA idiotype expression. The monoclonal B cells from 80% of the CLL patients produced IgG1 and those from 20% produced IgG3. None produced IgG2. In contrast to the known autoreactivity of IgM-producing CD5+ CLL cells (> 50% autoreactive), none of these IgG antibodies reacted significantly with the autoantigens tested. However, three did react significantly with autoantigen after artificially increasing antibody valency by crosslinking. Whereas five of the IgG molecules expressed a cross reactive idiotypic (CRI) marker characteristic of non-mutated kappa anti-DNA antibodies, three expressed a CRI displayed primarily on mutated IgG anti-DNA antibodies. Thus, some CD5+ human B cells can undergo an isotype class switch that for these CLL cells is biased against IgG2 and in favor of the IgG1 and IgG3. In their native state the IgG molecules secreted by these isotype-switched CD5+ cells have diminished autoreactivity, as compared to IgM-producing CLL cells. Since some of the IgG antibodies could be made auto- and poly-reactive by increasing antigen-binding valency, while others expressed idiotypic markers of mutated antibodies, certain of these CD5+ B cells probably utilize non-mutated Ig V genes coding for polyreactive antibodies, whereas others may use genes that have undergone somatic mutation and that code for more restricted specificities. Therefore, both valency and VH gene mutation may account for the diminished autoreactivity of these CD5+ B cell-derived IgG antibodies.

Adult↗
PubMed1994

The beneficial effect of the estrogen antagonist, tamoxifen, on experimental systemic lupus erythematosus.

OBJECTIVE: To determine the effects of the estrogen antagonist, tamoxifen, on the development and the course of experimental murine systemic lupus erythematosus (SLE). METHODS: SLE was induced in naive BALB/c female mice by injection of the human monoclonal anti-DNA antibody bearing the 16/6 idiotype (Id). Six weeks following immunization, when high levels of autoantibodies were demonstrated, the mice were treated with tamoxifen (200-800 micrograms/mouse twice a week) up to a period of 8 months. In several mouse groups tamoxifen treatment was started as late as one year following the immunization with the 16/6 Id when overt disease was already observed. RESULTS: Tamoxifen treatment had no effect on the 16/6 Id induced autoantibody production. However, the 16/6 Id immunized and tamoxifen treated mice demonstrated normal numbers of white blood cells (WBC) and thrombocytes while the untreated groups had significant leukopenia and thrombocytopenia. Similarly, persistent proteinuria and immune complex deposits in the kidneys were observed in the 16/6 Id immunized mice whereas no such deposits were found in kidney sections of 16/6 Id immunized mice that were treated with tamoxifen. Delayed tamoxifen treatment (starting a year following the immunization) also demonstrated beneficial therapeutic effects. CONCLUSION: These studies demonstrate therapeutic effects of tamoxifen on murine experimental SLE suggesting a possible role for this estrogen antagonist in the treatment of human SLE and related disorders.

Animals↗
PubMed1993

Anti-cardiolipin antibodies induce pregnancy failure by impairing embryonic implantation.

The antiphospholipid syndrome is characterized by thrombocytopenia, thrombosis, and recurrent fetal loss in association with anti-cardiolipin antibodies (ACAs) or lupus anti-coagulants. However, the causal role of these antibodies in the disease and the mechanisms by which the ACA may induce the syndrome are not clear. Recently, we have established an experimental mouse antiphospholipid syndrome induced by the mouse IgM monoclonal ACA designated 2C4C2. In the present study, we focused on the effects of immunization with the monoclonal ACA 2C4C2 on the outcome of pregnancies in BALB/c female mice. Four weeks after active immunization with the monoclonal ACA, a severe gestational failure with low pregnancy rates, low number of fetuses, and a high rate of resorptions was observed. Moreover, embryos obtained from the ACA-immunized females on day 3.5 of pregnancy were severely impaired, demonstrating developmental delay and abnormal morphology. These abnormal embryos failed also to develop in an in vitro implantation model. Furthermore, specific binding of the 2C4C2 ACA to the trophectoderm cell lineage of in vitro implanting normal embryos was observed. Thus, our studies demonstrate that the severe ACA-induced gestational failure results from an impairment of implantation and suggest that the ACA may react directly with the preimplantation embryos.

Abortion, Habitual↗
PubMed1993

Mechanism of autoimmune hemolytic anemia in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a malignant clonal expansion of CD5+B lymphocytes. The CD5+B lymphocytes have been postulated to produce autoantibodies. CLL patients may demonstrate features of autoimmunity including autoimmune hemolytic anemia. However, the origin of the autoantibodies causing the hemolysis is not clear. The present studies were performed to determine whether these autoantibodies are the products of the neoplastic B-CLL clones. Immunoglobulins (Ig) were eluted from washed red blood cells (RBC) obtained from two CLL patients at the time they had autoimmune (DAT-direct antiglobulin test-positive) hemolytic anemia. The light chain phenotypes of these eluted autoantibodies were determined and found to be monotypic with exact correlation to the light chain expressed on the surface of the B-CLL clones. Elutions from RBC of DAT negative patients or normal volunteers failed to demonstrate measurable amounts of Ig. In contrast, Ig eluted from RBC obtained from SLE patients with DAT positive hemolytic anemia found to be polyclonal autoantibodies exhibiting both light chain types. Furthermore, CD5+B lymphocytes obtained from the same two CLL patients (DAT+) produce, in vitro understimulation with phorbal myristate acetate (PMA), monoclonal antibodies which react and bind to RBC. Thus these studies provide direct evidence demonstrating that the antibodies causing the autoimmune hemolytic anemia in our two CLL patients are the products of the B-CLL neoplastic clones.

Aged↗
PubMed1993

Monoclonal anticardiolipin antibodies derived from mice with experimental lupus erythematosus: characterization and the induction of a secondary antiphospholipid syndrome.

The primary antiphospholipid syndrome and the antiphospholipid syndrome in systemic lupus erythematosus (SLE) patients (defined as secondary antiphospholipid syndrome) are characterized by the presence of anticardiolipin antibodies, thrombosis, thrombocytopenia, and recurrent fetal loss. To determine the role of anticardiolipin antibodies in the pathogenesis of antiphospholipid syndrome, monoclonal anticardiolipin antibodies were derived from mice in which experimental lupus was induced by a murine monoclonal anti-16/6 Id antibody. Two murine monoclonal anticardiolipin antibodies (2C4C2, 2C4D1) were generated and characterized. The 2C4C2, but not the 2C4D1, monoclonal antibody demonstrated remarkable lupus anticoagulant activity. Furthermore, these murine anticardiolipin monoclonal antibodies appear to recognize antigenic epitopes similar to those recognized by anticardiolipin antibodies found in sera of SLE patients. The monoclonal anticardiolipin antibody 2C4C2 was injected into naive female mice. Following immunization, the mice developed high titers of autoantibodies reacting with cardiolipin, DNA, nuclear extract, 16/6 and anti-16/6 Id, and anticardiolipin antibodies. As early as 8 weeks after immunization these mice exhibited significant leukopenia, thrombocytopenia, and proteinuria with immune complex glomerulonephritis. Moreover, mating of 2C4C2-injected mice with allogenic males resulted in low pregnancy rates and a low number of fetuses with a high percentage of fetal loss. These studies provide a new experimental model for secondary antiphospholipid syndrome demonstrating the role of anticardiolipin antibodies in the pathogenesis of this syndrome.

Animals↗
PubMed1993

Anti-CD23 monoclonal antibodies: comparisons of epitope specificities and modulating capacities for IgE binding and production.

A large battery of anti-CD23 mAb were compared for their epitope specificities and for their abilities to alter both IgE binding to cell-associated CD23 and IgE production in vitro in response to three sets of stimulants. The nine mAb tested can be divided into four families which define four antigenic epitopes (A-D) of CD23. Of these four families, two bind antigenic sites, (A and D) that appear to lie outside the IgE ligand binding site and two bind sites (B and C) that appear to be located within or close to this site, as determined by the abilities of appropriate mAb to alter IgE binding to CD23. The effects that these mAb had on IgE secretion by normal peripheral blood mononuclear cells (PBMNC) varied depending on the stimulant employed to induce IgE production. Interactions with epitope A, which was found to lie outside the ligand binding site and to be made more accessible by binding of mAb to other epitopes, had different effects on IgE production than interactions with the other epitopes. Indeed, mAb binding to this epitope lead to as much as a 10 fold enhancement in IgE biosynthesis induced by IL-4 alone or by IL-4 + hydrocortisone whereas interactions at the other sites resulted in almost complete inhibition of IgE production. In addition, mAb reactive with epitopes B and C had minimal effects on IgE production induced by IL-4 + anti-CD40 mAb whereas interactions at epitope A consistently enhanced IgE production. Finally, no apparent direct correlation was found between the ability of individual anti-CD23 mAb to alter IgE binding to cell-associated CD23 and their ability to modulate IgE production by PBMNC. These studies suggest that IgE binding to cell-associated CD23 does not have a major role in the de novo synthesis of IgE that involves CD23 interactions. In addition, the different effects that binding to epitope A vs B or C have on IgE synthesis suggest that molecular interactions between distinct portions of the CD23 molecule and other cell surface molecules expressed on the same B cell or adjacent communicating cells may lead to divergent cellular effects on IgE production. Finally these studies imply that only epitope A is involved in the generation of an IgE response through the CD40 pathway.

Animals↗
PubMed1991

Epitopes of the p70 and p80 (Ku) lupus autoantigens.

High titer autoantibodies to the Ku Ag, a DNA-protein complex containing 70- and approximately 80-kDa protein subunits (p70 and p80, respectively), are found in sera of certain patients with systemic lupus erythematosus and related disorders. Autoepitopes of the Ku Ag were identified and partially characterized by expressing fragments of the p70 and p80 cDNA as fusion proteins in bacteria. Systemic lupus erythematosus sera reacted on immunoblots with at least three epitopes of p70 (amino acids 560-609, 506-535, and 115-467), and three epitopes of p80 (amino acids 682-732, 558-681, and 1-374). These six antigenic regions had distinct amino acid sequences, and were also immunologically distinct, as determined by using immunoaffinity-purified auto-antibodies to particular epitopes. Detailed mapping of the strongly antigenic region near the C terminus of p70 revealed a complex conformational or discontinuous epitope, the antigenicity of which was abolished by deleting either amino acids 560-571 or 601-609. The C terminus of p80 may also contain a discontinuous or conformational epitope(s). Although only some sera reacted with p70 or p80 on immunoblots, all sera that immunoprecipitated the native Ku complex reacted with native Ku by ELISA, and inhibited the binding of mAb directed at epitopes of native Ku. Taken together, these studies indicate that anti-Ku autoantibodies target a diversity of independent epitopes located on p70, p80, and the intact Ku complex, and that a significant portion of the autoantibodies in most patients' sera is directed against conformational/discontinuous epitopes.

Antibody Specificity↗
PubMed1991

[Scurvy from self-imposed diet].

Scurvy, a rare disease, is still found today in malnourished patients. We recently diagnosed a case of scurvy in a 64-year-old woman resulting from a self-imposed diet. She had severe anemia and the characteristic gingival and skin lesions, which responded dramatically to ascorbic acid therapy. We report this case to make physicians aware of the possibility of scurvy and of its clinical symptoms.

Ascorbic Acid↗