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51.
Ataxia-telangiectasia (A-T) is a rare hereditary syndrome involving cerebellar degeneration, immunodeficiency, cancer risk, and radiosensitivity. Since the cloning of the A-T gene, ATM, in 1995, research on this pleiotropic disease and its molecular basis has expanded tremendously. ATM is a large protein kinase that appears to be one of the primary sensors of DNA strand-break damage. The vast majority of mutations in ATM result in truncation and destabilization of the protein, but certain missense and splicing errors have been shown to result in a less severe phenotype. A-T heterozygotes have been shown to have a slightly increased risk of cancer, but their increased in vitro radiosensitivity does not seem to result in any in vivo sensitivity. ATM does seem to act as a classic tumor suppressor gene in T-prolymphocytic leukemia, and LOH at the ATM locus is a common event in some tumor types, suggesting a general role for ATM in cancer. Recent work has shown the interaction of ATM with proteins involved in cell cycle control, and the direct phosphorylation of some of these interactors by ATM. ATM knockout mice have been created by several groups, and recapitulate the immunodeficiency, radiosensitivity, cancer risk, and fertility defects of A-T, although the effect on the cerebellum is slight. These diverse topics, and their integration into a global understanding of A-T, were the basis of the 7th International A-T Workshop. 相似文献
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Growth hormone (rGH) and prolactin (rPRL) secretory profiles were obtained before and after treatment with a dopamine receptor blocking agent, (+) butaclamol, in 10 male rats chronically implanted with right atrial cannulae. Mean rGH plasma concentrations, determined by planimetry, were reduced (202 +/- 20 ng/ml vs. 135 +/- 20ng/ml, P less than .01), but the basic configuration and periodicity of rGH secretory bursts were unaltered. Mean rPRL plasma concentrations were elevated (11.1 +/- 2.1 ng/ml vs 65.5 +/- 8.1 ng/ml, P less than .0005), but rPRL episodic secretion was still apparent. It is concluded that dopaminergic neurons have a minor role in facilitating episodic rGH secretion. Furthermore, persisting episodic rPRL secretion in rats administered a dopamine antagonist suggests that rPRL feedback inhibition does not inactivitate the neural mechanism generating episodic rPRL secretion. 相似文献
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The ability of polymorphonuclear leucocytes (PMNs) to migrate into the different corneal layers in the presence or absence of a chemotactic stimulus was investigated in rabbits. The epithelial and/or endothelial surfaces were damaged in some corneas and in others they were intact. One side of the cornea was kept in contact with a viable population of rabbit PMNs and the other side with a chemotactic agent (zymosan activated human serum). The migration of PMNs into the cornea was traced histologically. The PMNs could not penetrate intact epithelium and Descemet's membrane even under the influence of a chemotactic stimulus. The stroma allowed PMN migration only when the chemotactic agent was present. The endothelium offered no resistance to PMN invasion whether the chemotactic stimulus was present or not. 相似文献
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In seven of 30 consecutive patients with the adult respiratory distress syndrome, disseminated intravascular coagulation (DIC) developed. Increasing respiratory dysfunction characterized by decreased effective static compliance and increased hypoxemia coincided with the development of DIC. Patients in whom DIC developed were characterized by a high incidence of bleeding, gangrene of the extremities, renal dysfunction, mortality and autopsy evidence of fibrin microthrombi in the lungs, kidney and skin. In 12 of 23 patients who did not meet the criteria for DIC, the platelet count decreased by at least 50 per cent of the initial values at some time during their illness. Fibrin microthrombi were found in the lungs in the majority of the patients subjected to autopsy. These data support the concept that depostion of platelet on damaged pulmonary capillary endothelium may be more common in the adult respiratory distress syndrome than the DIC syndrome. 相似文献