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161.
By homology to the mgt gene (encoding a macrolide glycosyltransferase) from Streptomyces lividans, a 3.3-kb DNA fragment from the oleandomycin producer, Streptomyces antibioticus, was cloned and sequenced. Analysis of the sequence revealed the presence of the 3' end of a gene (ORF1) and two complete ORFs (ORF2 and oleD), all of them translationally coupled. The deduced product of the sequenced region of ORF1 contained the typical signature of integral membrane proteins responsible for the translocation of substrates across the membrane. The ORF2 product did not show significant similarity with proteins in databases, but contains an N-terminus leader peptide region characteristic of secreted proteins, and a lipid attachment site motif characteristic of membrane lipoproteins synthesized with a precursor signal peptide. The oleD product showed clear similarity with several UDP-glucuronosyl- and UDP-glycosyl-transferases from different origins and particularly with the mgt gene from S. lividans, and might encode a glycosyltransferase activity capable of inactivating macrolides. It is proposed that these three genes could participate in the intracellular glycosylation of oleandomycin and its secretion during antibiotic production. 相似文献
162.
HR Franklin GP Simonetti AC Dubbelman WW ten Bokkel Huinink BG Taal G Wigbout IA Mandjes OB Dalesio NK Aaronson 《Canadian Metallurgical Quarterly》1994,5(2):113-117
Human neutrophil PLD activity stimulated with GTP-gamma-S was reconstituted with recombinant ARF1 in cytosol-depleted cells. PMA-pretreatment of intact cells greatly enhanced the subsequent reconstitution of the ARF1-regulated PLD activity. This enhancement was only observed provided that the intact cells were pretreated with PMA, suggesting the stable recruitment of a cytosolic component, presumably protein kinase C, to the membranes. rARF1-reconstituted PLD activity was not dependent on MgATP, but could be considerably enhanced by MgATP. Maximal effects of MgATP were seen at 1 mM. This enhancement by MgATP could not be attributed to protein kinase C. Neomycin was found to inhibit ARF1-regulated PLD activity suggesting the requirement for polyphosphoinositides. We conclude: (i) that many of the observed effects of PMA may be dependent on the presence of the small GTP-binding protein, ARF, and (ii) polyphosphoinositides are required for ARF1-stimulated PLD activity. 相似文献
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WW Menninger 《Canadian Metallurgical Quarterly》1993,57(2):208-217
Violence is the ultimate maladaptive coping behavior manifested by a small but significant number of psychiatric patients. The management of the aggressive and dangerous patient depends on recognition of predisposing developmental experiences, cognitive and behavioral factors, and situational circumstances that potentiate a violent outburst. The author presents management guidelines, which stem from an understanding of the paranoid process, respect for the limited coping skills of the individual, and appropriate use of verbal, physical, and chemical interventions. 相似文献
165.
MP Thomas WW Webster RB Norgren DT Monaghan RA Morrisett 《Canadian Metallurgical Quarterly》1998,85(2):615-626
An important general question in neurobiology concerns the development and expression of the rich context of neuronal phenotypes, especially in relation to the diverse patterns of connectivity. Organotypic cultures of brain slices may offer distinct advantages for such studies if such a preparation survives, maintains a wide diversity of neuronal phenotypes and displays appropriate synaptic connections between regions. To address these requirements, we utilized long-term organotypic cultures of intact horizontal slices of rat forebrain and midbrain and assessed a variety of markers of phenotype in combination with functional tests of connectivity. This explant preparation displayed a distinct viability requirement such that the greatest explant survival was seen in slices taken from pups of less than postnatal day 7 and was independent of N-methyl-D-aspartate channel blockade. The anatomical features of the major brain regions (e.g., neocortex, striatum, septum, hippocampus, diencephalon and midbrain) were observed in their normal boundaries. The presence of cholinergic and catecholaminergic neurons was demonstrated with acetylcholinesterase histochemistry and tyrosine hydroxylase immunohistochemistry. Labelled neurons displayed multiple, regionally-appropriate cytoarchitectures and, in some cases, could be seen to project to brain regions in a manner quite similar to that seen in vivo. Finally, the direct demonstration of spontaneous and evoked interregional excitatory synaptic transmission was made using whole-cell patch-clamp recordings from striatal neurons which revealed an intact glutamate-using corticostriatal pathway. This simple explant preparation appears to contain a rich diversity of neuronal types and synaptic organization. Therefore, this preparation appears to have several distinct advantages for basic neurobiologic research since it combines long-term culture viability and many features of mature brain including complex interregional neuronal systems. 相似文献
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LS Dean M Mickel R Bonan DR Holmes WW O'Neill IF Palacios S Rahimtoola JN Slater K Davis JW Kennedy 《Canadian Metallurgical Quarterly》1996,28(6):1452-1457
OBJECTIVES: This study reports the long-term outcome of patients undergoing percutaneous balloon mitral commissurotomy who were enrolled in the National Heart, Lung, and Blood Institute (NHLBI) Balloon Valvuloplasty Registry. BACKGROUND: The NHLBI established the multicenter Balloon Valvuloplasty Registry in November 1987 to assess both short- and long-term safety and efficiency of percutaneous balloon mitral commissurotomy. METHODS: Between November 1987 and October 1989, 736 patients > or = 18 years old underwent percutaneous balloon mitral commissurotomy at 23 registry sites in North America. The maximal follow-up period was 5.2 years. RESULTS: The actuarial survival rate was 93 +/- 1% (mean +/- SD), 90 +/- 1.2%, 87 +/- 1.4% and 84 +/- 1.6% at 1, 2, 3 and 4 years, respectively. Eighty percent of the patients were alive and free of mitral surgery or repeat balloon mitral commissurotomy at 1 year. The event-free survival rate was 80 +/- 1.5% at 1 year, 71 +/- 1.7% at 2 years, 66 +/- 1.8% at 3 years and 60 +/- 2.0% at 4 years. Important univariable predictors of actuarial mortality at 4 years included age > 70 years (51% survival), New York Heart Association functional class IV (41% survival) and baseline echocardiographic score > 12 (24% survival). Multivariable predictors of mortality included functional class IV, higher echocardiographic score and higher postprocedural pulmonary artery systolic and left ventricular end-diastolic pressures (p < 0.01). CONCLUSIONS: Percutaneous balloon mitral commissurotomy has a favorable effect on the hemodynamic variables of mitral stenosis, and long-term follow-up data suggest that it is a viable alternative with respect to surgical commissurotomy in selected patients. 相似文献
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Bradykinin (BK) is an endogenous nonapeptide with potent vasodilator properties of the visceral circulation. BK alters vascular tone via two BK receptor subtypes, B1 and B2. Current experimental evidence suggests that the dilator action of BK in some vessels is mediated primarily by B2 receptor activation. In addition, there are reports that BK increases endothelial generation of vasodilator factors, such as nitric oxide (NO). The present study had two aims. First, to explore the role of BK-receptors in the pancreatic vasodilatatory and metabolic responses to BK. Second aim was to examine whether endogenous NO play a role in the mediation of BK-receptors induced pancreatic circulatory and metabolic activity. In anesthetized dogs, the superior pancreatico-duodenal artery blood flow (SPBF) was measured by ultrasonic blood flowmeter (Transonic System T-206), pancreatic microcirculatory blood flow (PBF) was determined by laser Doppler flowmetry (Periflux 4001 Master). Pancreatic oxygen consumption (PVO2) was calculated as the product of the arteriovenous oxygen difference (AVO2) across the pancreatic circulation and SPBF. Drugs were infused into the superior pancreatico-duodenal artery. BK (0.01-1.0 mg/kg/min) increased maximally SPBF by 180 +/- 15%, PBF by 208 +/- 22% and PVO2 by 145 +/- 11%, respectively. Pretreatment with B2-subtype receptor antagonist, D-Arg, [Hyp3, Thi5,8, D-Phe7] BK inhibited significantly BK-induced increase in SPBF, PBF and PVO2 by 86 +/- 8%, 73 +/- 7% and 85 +/- 6%, respectively. A nitric oxide synthesis inhibitor (L-NNA) administered i.v. at dose of 25 mg/kg 20 min before BK, inhibited significantly the pancreatic hyperemic and metabolic responses. The results presented emphasize an important role of B2 receptors in the mediation of pancreatic circulatory and metabolic responses to bradykinin. Endogenous NO plays a mediatory role in the pancreatic vascular and metabolic responses due to stimulation of B2-receptors. 相似文献