Assembly of an abundant endogenous major histocompatibility complex class II/peptide complex in class II compartments

To identify the intracellular site(s) of formation of an endogenous class II/peptide complex in a human B cell line, we employed kinetic pulse-chase labeling experiments followed by subcellular fractionation by Percoll density gradient centrifugation and immunogold labeling on ultrathin cryosections. For direct demonstration of assembly of such complexes, we used the monoclonal antibody YAe, which detects an endogenous complex of the mouse class II molecule I-Ab with a 17-amino acid peptide derived from the alpha chain of HLA-DR (DR alpha52-68). We show that in human B lymphocytes, these class II/peptide complexes assemble and transiently accumulate in major histocompatibility complex class II-enriched compartments before reaching the cell surface.     

15 beta-hydroxysteroids (Part IV). Steroids of the human perinatal period: the synthesis of 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one and its A/B-ring configurational isomers

In recent years several 15 beta-hydroxysteroids have emerged pathognomonic of adrenal disorders in human neonates of which 3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) was the first to be identified in the urine of newborn infants affected with congenital adrenal hyperplasia. In this investigation we report the synthesis of the three remaining 3 xi,5 xi-isomers, namely 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (3), 3 beta,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (7) and 3 beta,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (8) for their definitive identification in pathological conditions in human neonates. 3 beta,15 beta-Diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (11), a product of chemical synthesis was converted to the isomeric 3 and 7, while conversion of 15 beta,17 alpha-dihydroxy-4-pregnen-3,20-dione (4), a product of microbiological transformation, resulted in the preparation of 8. In brief, selective acetate hydrolysis of 11 gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5-pregnen-20-one (12) which on catalytic hydrogenation gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5 alpha-pregnan-20-one (13) a common intermediate for the synthesis of the 3 beta(and alpha),5 alpha-isomers. Hydrolysis of the 15 beta-acetate gave 7, whereas oxidation with pyridinium chlorochromate gave 15 beta-acetoxy-17 alpha-hydroxy-5 alpha-pregnan-3,20-dione (14) which on reduction with L-Selectride and hydrolysis of the 15 beta-acetate gave 3. Finally, hydrogenation of 4 gave 15 beta, 17 alpha-dihydroxy-5 beta-pregnan-3,20-dione (10) which on reduction with L-Selectride gave 8.     

Depression without sadness: functional outcomes of nondysphoric depression in later life

OBJECTIVES: We hypothesized that depressive symptoms not meeting full standard criteria for Major Depression would be associated with significant functional impairment among older adults over the course of a 13-year follow-up interval. Specifically, we developed criteria for a form of depression whose core symptoms did not include sadness or dysphoria. DESIGN: Population-based 13-year follow-up survey. SETTING: Community-dwelling adults living in East Baltimore in 1981. PARTICIPANTS: Subjects were the 1612 participants of the Baltimore sample of the Epidemiologic Catchment Area Program aged 50 years and older at the initial interview in 1981. MEASUREMENTS: The subjects were sorted into four categories based on their responses at baseline: (1) persons meeting standard criteria for Major Depression; (2) persons meeting alternative criteria for depression with dysphoria or (3) without dysphoria; and (4) a comparison category of persons not meeting any criteria for depression ("noncases"). The mortality and functional status of each group were compared after a 13-year follow-up interval. RESULTS: Compared with non-cases, participants aged 50 years and older who reported depressive symptoms but who denied sadness or dysphoria (nondysphoric depression) were at increased risk for death (relative risk (RR) = 1.70; 95% confidence interval (CI) (1.09, 2.67)), impairment in activities of daily living (RR = 3.76; 95% CI (1.73, 8.14)), impairment in instrumental activities of daily living (RR = 5.07; 95% CI (2.24, 11.44)), psychologic distress (RR = 3.68; 95% CI (1.47, 9.21)), and cognitive impairment (RR = 3.00; 95% CI (1.31, 6.89)) after a 13-year follow-up interval. The findings were not wholly explained by potentially influential baseline characteristics such as age, education, selected comorbid medical conditions, and functional status. CONCLUSION: Among adults aged 50 years and older, nondysphoric depression may be as important as Major Depression in relation to the development of functional disability and other long-term outcomes.     

氧饱和煤焦和二氧化碳气化煤焦的TPD—MS谱分析

氧饱和煤焦的TPD-MS谱中的CO_2脱附曲线是宽阔带状,在683K附近有一个脱附峰,CO脱附曲线有一个由963K主峰和1083K的肩峰组成的巨大脱附峰及一个在1473K附近的脱附峰。CO_2气化煤焦的TPD—MS谱只有一条CO脱附曲线,在1253和1473K附近突出两个脱附峰。用CO处理的煤焦样品的TPD-MS谱与CO_2气化煤焦样品的TPD-MS谱相似。由此推测仅有两种分别具有半醌型和环醚型结构的碳表面氧化物参与气化反应,并从结构角度解释了煤焦CO_2气化反应的机理。     

Stress-induced tau phosphorylation in mouse strains with different brain Erk 1 + 2 immunoreactivity

BACKGROUND: To our knowledge, the contribution of prothrombotic conditions to cerebral thromboembolism has never been prospectively studied in a large series of pediatric patients. METHODS: The Hospital for Sick Children, Toronto, Ontario, established a program in January 1992 to diagnose and treat children (term newborn to 18 years old) with arterial ischemic stroke or sinovenous thrombosis. The routine evaluation for prothrombotic conditions included plasminogen, antithrombin, protein C, free protein S, activated protein C resistance, IgG and IgM anticardiolipin antibody, and lupus anticoagulant. We analyzed samples taken within 2 years of the event. We report results on patients seen from January 1, 1992, to January 1, 1997. RESULTS: Ninety-two patients (47 males and 45 females) entered the program during the study interval. Patients ranged from newborn to 18 years in age. Arterial ischemic stroke occurred in 78% of patients while sinovenous thrombosis occurred in 22%. All were tested for prothrombotic disorders. One or more abnormal results were present in 35 (38%) of the 92 patients. The majority (21/35) had multiple abnormal test results. The abnormal test results were anticardiolipin antibody (33%), plasminogen (9.5%), activated protein C resistance (9%), protein C (7%), antithrombin (12.5%), lupus anticoagulant (8%), and free protein S (11.5%). Male sex predicted the presence of prothrombotic abnormalities (relative risk, 1.7; 95% confidence interval, 1.2-2.5), but stroke type (relative risk, 0.8; 95% confidence interval, 0.7-1.1), age group, and presence of other risk factors did not predict abnormal testing. CONCLUSIONS: A significant proportion (38%) of children with cerebral thromboembolism had evidence of prothrombotic conditions. In particular, there was a predominance of children with anticardiolipin antibody (33%). These data support a recommendation that children with cerebral thromboembolism be evaluated for prothrombotic disorders.     

Effect of cervical carcinoma in situ and its management on pregnancy outcome

Small decreases in hydration status can result in a dramatic decrement in athletic performance and greatly increase the risk of thermal injury. Because of its osmotic properties, which enable greater fluid retention than the ingestion of water alone, glycerol has been proposed as a hyperhydrating agent. In fact, glycerol is now commercially available and marketed as a sport supplement to be ingested with water or sport drinks; thus, dietitians need to be cognizant of this new addition to the sports nutrition table. The results of glycerol-induced hyperhydration research have been equivocal, most likely because of methodologic differences between studies, such as variations in the intensity of exercise, environmental conditions, and concentration or dose of glycerol administered. Although the suggested dosage of glycerol depends on body size and varies between manufacturers, 1 g/kg body weight with an additional 1.5 L fluid taken 60 to 120 minutes before competition is standard. Some test subjects reported feeling bloated or nauseated after ingesting glycerol. This review examines glycerol-induced hyperhydration research and the safety of ingesting glycerol, discusses commercial availability of glycerol, and makes recommendations for glycerol-induced hyperhydration research.