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951.
Histopathological features of Alzheimer's disease (AD) include extracellular deposits of amyloid beta (A beta) fibrils in the cores of senile plaques, intracellular neurofibrillary tangles (NFT) which are composed of paired helical filaments (PHF), and neuronal cell loss. The main component of PHF is highly phosphorylated tau protein. We identified a protein kinase converting normal tau into a PHF-like state. The kinase is tau protein kinase (TPK) I/glycogen synthase kinase (GSK)-3 beta. Using a neuronal cell culture system as an AD model, it was recognized that TPK I/GSK-3 beta plays a central role in AD pathology. We hypothesize that A beta-induced neuronal cell death occurs by the following mechanism. A beta inactivates PI3-kinase and activates TPK I/GSK-3 beta, which in turn phosphorylates and inactivates both tau and pyruvate dehydrogenase (PDH). After the ability of tau to promote microtubule assembly is diminished by phosphorylation, soluble tau molecules aggregate into PHF by an unknown mechanism. Destabilization of microtubule arrays causes inhibition of axonal transport and accumulation of amyloid precursor protein (APP). Phosphorylation of PDH inhibits the reaction converting pyruvate to acetyl-CoA, resulting in inhibition of energy metabolism and a decrease in acetylcholine, both of which are also characteristics of AD. These changes may lead to neuronal cell death.  相似文献   
952.
The kinetics of controlled release of basic fibroblast growth factor (bFGF) from polymers (sutures, polycarbonate, Hydron, and Elvax), biopolymers (alginate), and biomatrices (lens capsules), and conditions for storage of bFGF (temperature, plastic type, heparin) were evaluated in vitro. Tissue culture proliferation bioassays with 3T3 fibroblasts, showed that only lens capsules with bFGF had a sustained release of bFGF for up to three weeks. The other materials released all of the 'bound' bFGF with two hours or produced an inflammatory response in vivo. Therefore, the lens tissue had the most potential for controlled long-term delivery of bFGF in vivo. These studies emphasise the importance of in vitro analysis of release kinetics of growth factors from a range of materials as a basis for potential in vivo applications.  相似文献   
953.
954.
Theoretic basis of cooperation relationship between organizations are reviewed. Second one, these theoretic concepts are applied to the relationship between district and reference medical Centers and Services, focusing on main problems of that relationship. The relevant role of communication and its new technologies are also discussed.  相似文献   
955.
The common neural network modeling practice of representing the elements of a task domain in terms of a set of features lacks justification if the features are derived through some form of ad hoc preabstraction. By examining a featural similarity model related to established multidimensional scaling techniques, a neural network is developed that generates features from similarity data and attaches weights to these features. The network performs a constrained search of a continuous solution space to determine the features and uses a previously developed regularization technique to minimize the number of features it derives. The network is demonstrated on artificial data, from which it recovers known features and weights, and on two real data sets involving the similarity of a set of geometric shapes and the abstract conceptual similarities of the 10 Arabic numerals. On the basis of these results, the relationship between the multidimensional scaling approach adopted by the network and an alternative additive clustering approach to feature extraction is discussed.  相似文献   
956.
OBJECTIVE: To determine the techniques used for the etiological diagnosis of community-acquired pneumonia in patients admitted to the intensive care unit (ICU) and to describe the predominant causative organisms as well as prognostic factors of ICU mortality. PATIENTS AND METHODS: A total of 262 patients with community-acquired pneumonia admitted to 26 ICUs between 1 November of 1991 and 31 October of 1992 were included in a prospective, open, multicenter study. RESULTS: The diagnostic techniques most frequently used were blood culture (243 cases) and simple tracheal aspirate (166 cases). Simple tracheal aspirate (58.4%), bronchoalveolar lavage (47.7%), and protected-specimen brush (44.2%) were the techniques that showed the highest diagnostic reliability. In 220 cases, techniques considered of high diagnostic probability were employed. With the use of these procedures, the most frequent causative pathogens were Streptococcus pneumoniae (13.6%) and Legionella pneumophila (9.5%). In 100 cases (45.5%), no pathogen was isolated. A total of 88 patients (33.6%) died during the ICU stay. Predictive variables of poor outcome selected by means of a multivariate analysis were as follows: multisystemic failure (OR = 28.6; 95% CI: 12.8-65.1; p = 0.0001), APACHE II at the time of ICU admission (OR = 5.3; 95% CI: 2.5-11.3; p = 0.0001), progression and/or spread of lung infection (OR = 4.5; 95% CI: 2.4-8.4; p = 0.0001), and shock on admission (OR = 8.48; 95% CI: 4.5-15.9; p = 0.0001). CONCLUSIONS: In 45.5% of patients with community-acquired pneumonia admitted to ICU, no causative pathogen was identified. The prognosis of these patients was influenced by the severity of disease assessed by APACHE II score and presence of multisystemic failure and shock at the time of ICU admission.  相似文献   
957.
Among the spliceosomal snRNAs, U2 has the most extensive modifications, including a 5' trimethyl guanosine (TMG) cap, ten 2'-O-methylated residues and 13 pseudouridines. At short times after injection, cellularly derived (modified) U2 but not synthetic (unmodified) U2 rescues splicing in Xenopus oocytes depleted of endogenous U2 by RNase H targeting. After prolonged reconstitution, synthetic U2 regenerates splicing activity; a correlation between the extent of U2 modification and U2 function in splicing is observed. Moreover, 5-fluorouridine-containing U2 RNA, a potent inhibitor of U2 pseudouridylation, specifically abolishes rescue by synthetic U2, while rescue by cellularly derived U2 is not affected. By creating chimeric U2 molecules in which some sequences are from cellularly derived U2 and others are from in vitro transcribed U2, we demonstrate that the functionally important modifications reside within the 27 nucleotides at the 5' end of U2. We further show that 2'-O-methylation and pseudouridylation activities reside in the nucleus and that the 5' TMG cap is not necessary for internal modification but is crucial for splicing activity. Native gel analysis reveals that unmodified U2 is not incorporated into the spliceosome. Examination of the U2 protein profile and glycerol-gradient analysis argue that U2 modifications directly contribute to conversion of the 12S to the 17S U2 snRNP particle, which is essential for spliceosome assembly.  相似文献   
958.
This study examines ethnic differences in sexual socialization and attitudes, sexual history and current practices, and the effects of treatment in 147 African American and White breast cancer survivors. Sex-related research in younger healthy populations has shown that cultural values associated with ethnicity influence sexual functioning, but small numbers of African American participants in previous research in breast cancer survivors has limited what we know about that population. In this study, there were few differences between the 2 ethnic groups in a predominantly well-educated, high-income, highly functional sample. However, African American women were significantly less likely to be comfortable with and to practice oral sex, self-touching, and masturbatory behaviors. White women were more likely to report that breast cancer had a negative impact on their sex lives. These differences in sexual repertoire and functioning should be noted by health care practitioners treating the sexual sequelae of breast cancer treatment.  相似文献   
959.
960.
The relationship between adolescent egocentrism and post-formal thinking was examined in 163 college undergraduates. Participants were administered the Imaginary Audience Scale and the Social Paradigm Belief Inventory. Results showed that females had higher levels of adolescent egocentrism than did males. A weak negative correlation between egocentrism and cognitive reasoning was found for females during late adolescence. The findings are consistent with Peterson and Roscoe's (1991) study of egocentrism in older adolescent females.  相似文献   
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