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Calcium-phospholipid-dependent protein kinase (PKC) has long been suggested to play an important role in modulating synaptic efficacy. We have created a strain of mice that lacks the gamma subtype of PKC to evaluate the significance of this brain-specific PKC isozyme in synaptic plasticity. Mutant mice are viable, develop normally, and have synaptic transmission that is indistinguishable from wild-type mice. Long-term potentiation (LTP), however, is greatly diminished in mutant animals, while two other forms of synaptic plasticity, long-term depression and paired-pulse facilitation, are normal. Surprisingly, when tetanus to evoke LTP was preceded by a low frequency stimulation, mutant animals displayed apparently normal LTP. We propose that PKC gamma is not part of the molecular machinery that produces LTP but is a key regulatory component.  相似文献   
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OBJECTIVE: To determine the actual use of 'statin' therapy for primary and secondary prevention and the potential effect of using the Sheffield Table for primary prevention of coronary heart disease upon 'statin' use in a consultant-run Hypertension and Cardiovascular Risk Clinic. DESIGN: Prospective audit of the current use of cholesterol-lowering therapy and the effect of implementing the criteria used in the Sheffield Table and the Scandinavian Simvastatin Study for cholesterol lowering in 'at risk' patients upon statin use in a consultant-led cardiovascular risk clinic. SETTING: The Aberdeen Hypertension Clinic. RESULTS: A total of 1500 patients were reviewed of which 416 (27.7%) had experienced at least one clinical manifestation of atherosclerotic cardiovascular disease (CVD) and 392 (94%) of these had a total cholesterol measured of whom 298 (76%) had a total cholesterol >5.5 mmol/l. Only 11.2% of eligible patients were actually receiving lipid-lowering treatment for secondary prevention. A total of 1084 patients with no prior cardiovascular disease were identified, 97 (8.9%) were excluded because of age. Using the Sheffield Table, 92 (9.4%) of these patients were eligible for statin therapy and only six of the 92 patients were actually receiving treatment. CONCLUSIONS: The results of this study reveal that even in a consultant-led cardiovascular prevention clinic there is a significant discrepancy between optimal evidence-based management and the actual delivery of clinical care. Seventy-two per cent and 9.3% of patients attending the clinic were eligible for statin treatment for secondary and primary prevention, respectively. However, only 11.2% of patients suitable for secondary prevention and 6.5% of patients suitable for primary prevention were actually receiving appropriate lipid-lowering therapy. Considering the proven benefit of this form of medical intervention the results of this study are of real importance to practising clinicians and patients alike.  相似文献   
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Under the sponsorship of the U.S. National Science Foundation, CHI Research, Inc. developed the bibliometric indicators for the U.S. National Science Board'sScience Indicators Reports starting withScience Indicators 1972. In the work reported here, for the Commission of the European Communities, CHI has extended the Science Indicators techniques and database to a study of publication, coauthorship and citation within 28 scientific fields related to various European Community programs.Perhaps the most important finding of the research was that internationally coauthored papers — papers authored by scientists affiliated with institutions in more than one EC country — were cited two times as highly as papers authored by scientists working at a single institution within a single country. These EC-EC internationally coauthored papers were cited as highly as EC-Non EC and Non-EC papers. This indicates that the internationally linked European science is of as high impact as any other science in the world.A second key finding was that, after compensating for national scientific size, the degree of international coauthorship did not appear to be particularly dependent upon size. However, linguistic and cultural factors were found to be very strong. The patterns of coauthorship amongst the European countries are far from homogeneous, and are quite heavily affected by linguistic, historical, and cultural factors.Finally, it was found that international coauthorship is increasing steadily, both within and outside of the Community, with some evidence that international cooperation is increasing more rapidly in scientific fields that have been targeted by the Commission.This work has been sponsored by the MONITOR programme of the Commission of the European Communities.  相似文献   
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This research supports the hypothesis that the Trust Vector model can be modified to fit the CyberCraft Initiative, and that there are limits to the utility of historical data. This research proposed some modifications and expansions to the Trust Model Vector, and identified areas for future research.  相似文献   
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Tyrosine hydroxylase (TyrOH) catalyzes the conversion of tyrosine to L-DOPA, the rate-limiting step in the biosynthesis of the catecholamines dopamine, adrenaline, and noradrenaline. TyrOH is highly homologous in terms of both protein sequence and catalytic mechanism to phenylalanine hydroxylase (PheOH) and tryptophan hydroxylase (TrpOH). The crystal structure of the catalytic and tetramerization domains of TyrOH reveals a novel alpha-helical basket holding the catalytic iron and a 40 A long anti-parallel coiled coil which forms the core of the tetramer. The catalytic iron is located 10 A below the enzyme surface in a 17 A deep active site pocket and is coordinated by the conserved residues His 331, His 336 and Glu 376. The structure provides a rationale for the effect of point mutations in TyrOH that cause L-DOPA responsive parkinsonism and Segawa's syndrome. The location of 112 different point mutations in PheOH that lead to phenylketonuria (PKU) are predicted based on the TyrOH structure.  相似文献   
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A case-mix classification system for medical rehabilitation   总被引:2,自引:0,他引:2  
Dissatisfaction with Medicare's current system of paying for rehabilitation care has led to proposals for a rehabilitation prospective payment system, but first a classification system for rehabilitation patients must be created. Data for 36,980 patients admitted to and discharged from 125 rehabilitation facilities between January 1, 1990, and April 19, 1991, were provided by the Uniform Data System for Medical Rehabilitation. Classification rules were formed using clinical judgment and a recursive partitioning algorithm. The Functional Independence Measure version of the Function Related Groups (FIM-FRGs) uses four predictor variables: diagnosis leading to disability, admission scores for motor and cognitive functional status subscales as measured by the Functional Independence Measure, and patient age. The system contains 53 FRGs and explains 31.3% of the variance in the natural logarithm length of stay for patients in a validation sample. The FIM-FRG classification system is conceptually simple and stable when tested on a validation sample. The classification system contains a manageable number of groups, and may represent a solution to the problem of classifying medical rehabilitation patients for payment, facility planning, and research on the outcomes, quality, and cost of rehabilitation.  相似文献   
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Vibrio cholerae causes epidemic diarrhea throughout the world. Fluid replacement is the primary therapy for cholera; however, high mortality rates often necessitate the use of antibiotics. V. cholerae, like most bacteria, has developed resistance to some antibiotics. In the early 1990s a new serotype strain, Bengal 0139, began a new wave of cholera epidemics. Bengal isolates showed unique trends in antimicrobial resistance. Many clinical laboratories use automated antibiotic susceptibility testing for V. cholerae. It is important to know if automated susceptibility test results for V. cholerae coincide with reported trends in antibiotic susceptibility. In the present study, we used the Vitek automated susceptibility system to determine the susceptibilities of 79 V. cholerae O1 isolates, 100 O139 isolates, and 112 non-O1 isolates. Vitek susceptibilities for V. cholerae showed a good correlation with preestablished epidemiological data. Although the new O139 serogroup showed a trend of increased resistance to trimethoprim-sulfamethoxazole and nitrofurantoin, it was more susceptible to ampicillin than previous serogroup O1 and non-O1 strains. Regardless of serogroup, > or = 98% of the V. cholerae isolates tested were susceptible to most antibiotics tested by us. It is important to continue susceptibility testing of all new isolates of V. cholerae because of emerging resistant strains. However, V. cholerae remains susceptible to most of the available antibiotics.  相似文献   
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