Ganglioside GM2-activator protein and vesicular transport in collecting duct intercalated cells.
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This study describes the molecular characterization of an antigen defined by an autoantibody from a woman with habitual abortion as GM2-activator protein. The patient showed no disorder of renal function. Accidentally with routine serum screening for autoantibodies, an immunoreactivity was found in kidney collecting duct intercalated cells. Three distinct patterns of immunostaining of intercalated cells were observed: staining of the apical pole, basolateral pole, and diffuse cytoplasmic labeling. Ultrastructurally, the immunoreactivity was associated with "studs," which represent the cytoplasmic domain of the vacuolar proton pump in intercalated cells. This pump is subjected to a shuttling mechanism from cytoplasmic stores to the cell membrane, which exclusively occurs in intercalated cells. Peptide sequences of a 23-kD protein purified from rat kidney cortex showed complete identity with corresponding sequences of GM2-activator protein. In the brain, GM2-activator protein is required for hexosaminidase A to split a sugar from ganglioside GM2. Because neither ganglioside GM2 nor GM1 (its precursor) is present in significant amounts in the kidney, the previous finding that this tissue contains the highest level of activator protein in the body was confusing. In this study, a novel role for GM2-activator protein in intercalated cells is proposed, and possible roles in the shuttling mechanism are discussed. (+info)
Factor V Leiden and antibodies against phospholipids and protein S in a young woman with recurrent thromboses and abortion.
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We describe the case of a 39-year-old woman who suffered two iliofemoral venous thromboses, a cerebral ischemic infarct and recurrent fetal loss. Initial studies showed high levels of antiphospholipid antibodies (APAs) and a moderate thrombocytopenia. After her second miscarriage, laboratory diagnosis revealed that the woman was heterozygous for the factor V Leiden mutation and had a functional protein S deficiency as well as anti-protein S and anti-beta 2-glycoprotein I antibodies. The impairment of the protein C pathway at various points could well explain the recurrent thromboses in the patient and supports the role of a disturbed protein C system in the pathophysiology of thrombosis in patients with APAs. (+info)
Possible mechanisms of immunotherapy for maintaining pregnancy in recurrent spontaneous aborters: analysis of anti-idiotypic antibodies directed against autologous T-cell receptors.
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We examined whether immunotherapy for recurrent spontaneous abortion (RSA) using paternal lymphocytes induces anti-T-cell receptor (TCR) idiotypic antibodies in RSA patients. The sera of these patients were assessed for inhibitory activity against mixed lymphocyte reactions (MLR) between maternal responder cells and paternal stimulator cells. Sera of four of the five women who maintained pregnancy successfully after immunotherapy showed significant MLR inhibition, whereas none of the five women who had unsuccessful pregnancies showed significant MLR inhibition. These sera inhibited the MLR of autologous responder T-cells, when stimulated with lymphocytes having the same HLA-DR antigens as the patient's husband, but not when stimulated with lymphocytes having unrelated HLA-DR antigens. This MLR inhibitory activity was absorbed by autologous maternal T-lymphoblasts induced by stimulation with lymphocytes having the paternal HLA-DR type but not by those induced by stimulation with lymphocytes having other HLA-DR types. The maternal serum inhibited the proliferation of autologous T-cells, but not of non-autologous T-cells, stimulated with paternal lymphocytes. These results indicate that anti-TCR idiotypic antibodies were induced in RSA patients by immunotherapy. These antibodies may contribute to maintaining pregnancy by negatively regulating maternal T-cells directed against HLA-DR antigens of the fetus. (+info)
Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study.
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The aim of this study was to evaluate the therapeutic efficacy of intravenous immunoglobulin (IVIG) in the prevention of recurrent spontaneous abortion (RSA). In a double-blind, randomized, placebo-controlled study, 41 women with a history of unexplained recurrent spontaneous abortion were treated with IVIG or saline infusions during pregnancy. The birth of a child was considered a successful outcome. The overall success rate was 77% in the IVIG group compared with 79% in the placebo group. For women with primary RSA the success rates were 82 (IVIG) and 89% (placebo), and for women with secondary RSA the rates were 73 (IVIG) and 70% (placebo). We found no statistically significant difference in treatment results between IVIG and placebo. (+info)
Neospora caninum infection and repeated abortions in humans.
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To determine whether Neospora caninum, a parasite known to cause repeated abortions and stillbirths in cattle, also causes repeated abortions in humans, we retrospectively examined serum samples of 76 women with a history of abortions for evidence of N. caninum infection. No antibodies to the parasite were detected by enzyme-linked immunosorbent assay, immunofluorescence assay, or Western blot. (+info)
Resection of uterine septum using gynaecoradiological techniques.
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This paper presents further refinements in our technique for the resection of uterine septum. Fourteen patients [infertility (n = 9) and recurrent miscarriages (n = 5)] underwent in-office resection of a uterine septum under fluoroscopic control. The main outcome measure was complete resection of uterine septum. Resections were carried out using either hysteroscopic scissors in combination with a specially designed uterine balloon catheter, or microlaparoscopy scissors in conjunction with a cervical cannula. In all patients the septum was successfully resected without any intra-operative complications. We conclude that ambulatory gynaecoradiological resection of uterine septa is a safe and simple procedure. It avoids utilization of expensive operating room time, general anaesthesia, and some complications associated with hysteroscopic resection, such as fluid retention and electrolyte imbalance. (+info)
Endometriosis and unexplained recurrent spontaneous abortion: pathological states resulting from aberrant modulation of natural killer cell function?
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The observation that natural killer (NK) cell activity is abnormally low in endometriosis patients and abnormally high in women with otherwise unexplained recurrent spontaneous abortion represents, at present, an intriguing curiosity. There is evidence suggesting that these conditions are associated with an opposite regulation of NK cell behaviour. This review discusses these observations and potential relationships. (+info)
Implications of sperm chromosome abnormalities in recurrent miscarriage.
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PURPOSE: Our purpose was to assess the existence of sperm chromosome abnormalities in recurrent pregnancy loss in an assisted reproduction program. METHODS: In this prospective study, 12 sperm samples from couples undergoing in vitro fertilization with two or more first-trimester spontaneous abortions were analyzed. Diploidy and disomy in decondensed sperm nuclei were assessed for chromosomes 13, 18, 21, X, and Y using two- and three-color fluorescence in situ hybridization. RESULTS: Sex chromosome disomy in sperm samples from recurrent abortion couples was significantly increased compared to that from internal controls (0.84% vs 0.37%). In a subpopulation of seven couples who underwent oocyte donation, mean frequencies for sex chromosome disomy (1%) were even higher and diploidy (0.43%) was also significantly increased. CONCLUSIONS: These results suggest an implication of sperm chromosome abnormalities in some cases of recurrent pregnancy loss. (+info)