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Major discoveries have been made of new type-I and type-III peptidomimetic inhibitors of peptide-derived systems. Innovative reversible inhibitors of cysteine proteases and renin, and additional examples of peptidomimetic inhibitors of interleukin-1 beta-converting enzyme, neutral endopeptidase, herpes simplex virus protease, thrombin, HIV protease, Ras farnesyltransferase, the RGD motif, Factor Xa and various aspartic proteases have been discovered. 相似文献
233.
Pax3 contains two structurally independent DNA-binding domains, a paired domain (PD) and a homeodomain (HD). Biochemical and mutagenesis studies have shown that both domains are functionally interdependent. In particular, it has been shown that the PD can regulate the DNA-binding specificity and dimerization potential of the HD. To delineate Pax3 protein segments that are involved in the regulation of HD DNA-binding, a series of chimeric proteins were created in which the HD and linker region were gradually replaced with corresponding sequences from a heterologous HD protein, Phox. Characterization of chimeric proteins by electrophoretic mobility shift analysis (EMSA) suggests that a portion of the linker region contributes to the functional interaction between the PD and HD. In addition, stepwise removal of sequences from the Pax3 PD was used to define regions within this domain that are involved in the regulation of HD DNA-binding. EMSA of these proteins in the context of the chimeric Pax3/Phox backbone provided two key findings: (i) the C-terminal subdomain of the PD does not play a major role in the regulation of HD DNA-binding and (ii) the N-terminal subdomain and, in particular, the second alpha-helix are essential for modulation of HD DNA-binding. Significantly, deletion of helix 2 was found to be sufficient to uncouple regulation of HD DNA-binding by the PD. 相似文献
234.
Although the importance of the father for the development of the child is well known and although an increased presence of the father in the family system is often demanded, processes of active shutting out the father occur. The deterioration of relation between father and child is not seen as a result of pathological male personality, but rather as a result of family or couple system. The special situation for counsellors of such cases is discussed. 相似文献
235.
BACKGROUND: Chymotrypsin (CT) and CT-like enzymes contribute to the dynamics of metabolism by their participation in digestion, peptide hormone generation and catabolism, fertilization of ova and inhibition of thrombin-induced platelet aggregation, among other processes. The frequency of pancreatitis is observably higher in alcoholics, and pancreatic enzymes have been associated with localized vascular damage, thrombosis and pancreatic necrosis. METHODS: Since CT is a major pancreatic enzyme and may serve as a link between pancreatitis, coagulopathy, and alcoholism, the affect of acetaldehyde (AcH) the primary metabolite of ethanol, upon the enzyme and upon the influence of human serum thereon was studied. RESULTS: It was observed that CT activity upon glutaryl-L-phenylalanine-b-naphthylamide was inhibited to the extent of 23.7%, 52.5%, and 96.7% by 44.7, 89.4, and 447 mmol/L AcH in a fluorometric assay whereby the enzyme was dialyzed to remove excess AcH prior to assay. The p values were < 0.04. Aliquots of human serum (10 microL, 20 microL, 30 microL, 40 microL, 50 microL, and 100 microL) inhibited 40 micrograms of CT by 13%, 37.7%, 65.3%, 89.8%, and 92.8%, respectively (n = 6; p = < 0.05). The serum did not hydrolyze the fluorogenic substrate. On the other hand, AcH added to serum at 447, 224, 112, or 56 mmol/L resulted in 42.6%, 42.6%, 52.9%, and 60.3% inhibition of CT relative to a 69.1% inhibition of the enzyme by serum alone (n = 6; = p < 0.01). CONCLUSIONS: These data show that AcH clearly decreases the antichymotryptic activity of serum (consisting of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, and alpha 2-macroglobulin). The incomplete inactivation of chymotrypsin by serum and partial inactivation of CT inhibitor(s) by AcH suggest the possibility that CT leaked into the circulation, (in alcoholic pancreatitis) may be available in blood to lower the clotting potential induced by thrombin-activated platelets, and that a greater amount of CT might be available in the blood of alcoholics, thereby contributing, in part, to the prolongation of clotting times. 相似文献
236.
GM McCarthy JA Augustine AS Baldwin PA Christopherson HS Cheung PR Westfall RI Scheinman 《Canadian Metallurgical Quarterly》1998,273(52):35161-35169
237.
L Beck AC Karaplis N Amizuka AS Hewson H Ozawa HS Tenenhouse 《Canadian Metallurgical Quarterly》1998,95(9):5372-5377
Npt2 encodes a renal-specific, brush-border membrane Na+-phosphate (Pi) cotransporter that is expressed in the proximal tubule where the bulk of filtered Pi is reabsorbed. Mice deficient in the Npt2 gene were generated by targeted mutagenesis to define the role of Npt2 in the overall maintenance of Pi homeostasis, determine its impact on skeletal development, and clarify its relationship to autosomal disorders of renal Pi reabsorption in humans. Homozygous mutants (Npt2(-/-)) exhibit increased urinary Pi excretion, hypophosphatemia, an appropriate elevation in the serum concentration of 1,25-dihydroxyvitamin D with attendant hypercalcemia, hypercalciuria and decreased serum parathyroid hormone levels, and increased serum alkaline phosphatase activity. These biochemical features are typical of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a Mendelian disorder of renal Pi reabsorption. However, unlike HHRH patients, Npt2(-/-) mice do not have rickets or osteomalacia. At weaning, Npt2(-/-) mice have poorly developed trabecular bone and retarded secondary ossification, but, with increasing age, there is a dramatic reversal and eventual overcompensation of the skeletal phenotype. Our findings demonstrate that Npt2 is a major regulator of Pi homeostasis and necessary for normal skeletal development. 相似文献
238.
239.
240.
S Houston 《Canadian Metallurgical Quarterly》1994,40(2):48-52
BACKGROUND: The validity of excluding bereavement-related depressive episodes which satisfy all the criteria of major depression is examined in this community study. METHOD: A total of 658 subjects were interviewed in their homes using the Diagnostic Interview Schedule. The length of the episodes of depression, the dysfunction they caused, and the frequency of seeking and receiving treatment were assessed. RESULTS: The risk of recurrence did not differ whether the depressive episodes that satisfy the DSM-III-R criteria of major depression were or were not related to bereavement. CONCLUSIONS: Excluding from the repertoire of depressions all those related to external stressors might need more research, but singling out those related to bereavement does not seem to be supported by our community-based data. 相似文献