Acquired anaemias and polycythaemia.
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Biomedical subjects
Publications and source records attributed to J M Durand.
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OBJECTIVE: Recent studies have shown that in vitro endothelial cells are activated by antiphospholipid antibodies and may support leukocyte adhesion. We studied levels of soluble intercellular adhesion molecule 1 (sICAM-1, sCD54), soluble vascular cell adhesion molecule 1 (sVCAM-1, sCD106), and soluble E-selectin (soluble endothelial leukocyte adhesion molecule 1 [sELAM-1, sCD62E]) in sera from patients with primary antiphospholipid syndrome (primary APS), and compared them with those from patients with systemic lupus erythematosus-associated APS (SLE-APS) or pure SLE, as well as with those from 2 control groups composed of healthy volunteers and patients with thrombosis unrelated to autoimmune diseases. METHODS: Serum samples from 24 patients with primary APS, 15 patients with SLE-APS, 22 patients with pure SLE, 48 control patients with thrombosis, and 18 healthy volunteers were examined using enzyme-linked immunosorbent assays specific for sICAM-1, sVCAM-1, and sELAM-1. RESULTS: Serum levels of sVCAM-1, but not sICAM-1 or sELAM-1, were significantly increased in all patient study groups compared with thrombosis control patients and healthy volunteers, but did not differ between the groups of patients with primary APS, SLE-APS, or pure SLE. Concentrations of sVCAM-1 were significantly higher in primary APS or SLE-APS patients with severe, recurrent thrombosis and were negatively correlated with platelet counts in primary APS patients. In patients with primary APS, sVCAM-1 levels were higher if there was thrombotic kidney involvement and correlated with creatinemia. CONCLUSION: Serum sVCAM-1 concentrations are increased in patients with primary APS, especially those with repeated thrombotic events or kidney involvement. These findings suggest that endothelial/ monocyte interaction may be important in the pathogenesis of primary APS.
INTRODUCTION: The objective of this work was to review current data about the physiopathology, clinical features, and treatment of thrombotic thrombocytopenic purpura (Moschowitz's syndrome). CURRENT KNOWLEDGE AND KEY POINTS: Thrombotic thrombocytopenic purpura is a rare disorder characterized by widespread thrombotic injuries of platelets in the microcirculation. Its physiopathology has been elucidated recently. Evidence of a deficiency of Von Willebrand's factor-cleaving protease would be due to either IgG antibodies in the acute form of the disease or constitutional deficiency in the chronic form of the disease. FUTURE PROSPECTS AND PROJECTS: Plasma exchange is the current reference treatment. However, in the light of recent publications, either infusions of concentrates of purified enzyme or more intensive immunosuppressive therapy would be more specific.
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INTRODUCTION: Ovarian hemorrhage with hemoperitoneum is a rare but serious complication of ovulation related to rupture of either the corpus luteum or functional cyst. It is due to treatment using oral indirect anticoagulant and specifically affects young women. CURRENT KNOWLEDGE AND KEY POINTS: We review cases that were reported since the initial description by Weseley in 1957. The main indications for oral indirect anticoagulant are thrombophlebitis and valvular cardiac prosthesis. Pelvic pain with peritoneal irritation is the most common symptom in more than one third of the patients. An initial collapse is reported in 22% of the cases. Surgery is the main treatment. Mortality is 3% and recurrences occur in nearly 25% of the patients. FUTURE PROSPECTS AND PROJECTS: Potential ovarian hemorrhage should be investigated when a woman taking oral indirect anticoagulant develops acute abdominal pain. Surgery should be conservative and whenever possible, should include celioscopy. Systematic ovarian blockade should be discussed in women taking long-term oral indirect anticoagulant.
Full expression of the virulence genes of Shigella flexneri requires the presence of two modified nucleosides in the tRNA [queuosine, Q34, present in the wobble position (position 34) and 2-methylthio-N6-isopentenyladenosine (ms2i6A37, adjacent to and 3' of the anticodon)]. The synthesis of these two nucleosides depends on the products of the tgt and miaA genes respectively. We have shown that the intracellular concentration of the virulence-related transcriptional regulator VirF is reduced in the absence of either of these modified nucleosides. The intracellular concentration of VirF is correlated with the expression of the virulence genes. Overproduction of VirF in the tgt and the miaA mutants suppressed the less virulent (tgt) or the avirulent (miaA) phenotypes respectively, caused by the tRNA modification deficiency. This suggests that the primary result of undermodification of the tRNA is a poor translation of virF mRNA and not of any other mRNA whose product acts downstream of the action of VirF. Shigella showed no virulence phenotypes at 30 degrees C, but forced synthesis of VirF at 30 degrees C induced the virulence phenotype at this low temperature. In addition, removal of the known gene silencer H-NS by a mutation in its structural gene hns increased the synthesis of VirF at low temperature and thus induced a virulent phenotype at 30 degrees C. Conversely, decreased expression of VirF at 37 degrees C induced by the addition of novobiocin, a known inhibitor of gyrase, led to an avirulent phenotype. We conclude that tRNA modification, temperature and superhelicity have the same target - the expression of VirF - to influence the expression of the central regulatory gene virB and thereby the virulence of Shigella. These results further strengthen the suggestion that the concentration of VirF is the critical factor in the regulation of virulence in Shigella. In addition, they emphasize the role of the bacterial translational machinery in the regulation of the expression of virulence genes which appears here quantitatively as important as the well-established regulation on the transcriptional level.
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Transfer RNA modification improves the rate of aa-tRNA selection at the A-site and the fitness in the P-site and thereby prevents frameshifting according to a new model how frameshifting occurs [Qian et al. (1998) Mol. Cell 1, 471-482]. Evidence that the presence of various modified nucleosides in tRNA also influences central metabolism, thiamine metabolism, and bacterial virulence is reviewed.
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