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Susan Yung Heinz Hausser Gareth Thomas Liliana Schaefer Hans Kresse Malcolm Davies 《Peritoneal dialysis international》2004,24(2):147-155
OBJECTIVE: Previous studies have shown that decorin and biglycan account for over 70% of the proteoglycans (PGs) synthesized by human peritoneal mesothelial cells (HPMCs). Since these PGs are involved in the control of cell growth, cell differentiation, and matrix assembly, we investigated their turnover in cultured HPMCs. METHODS: Confluent HPMCs were metabolically labeled with [35S]-sulfate and the labeled products isolated from the cell medium and the cell layer characterized by sensitivity to bacterial eliminases. Experiments were undertaken with exogenous labeled decorin, and its metabolic state was studied. RESULTS: In a 24-hour labeling period, 75% of the newly synthesized chondroitin sulfate/dermatan sulfate (CS/DS) PGs appeared in the culture medium, the majority of which (90%) was decorin. In the cell layer, protein-free glycosaminoglycan (GAG) chains accounted for 21% of the total CS/DS at 24 hours and exhibited constant specific activity at 12-16 hours. The latter material was turned over with a half-life of approximately 2.5 hours. Exogenous decorin underwent receptor-mediated endocytosis and subsequent intracellular degradation. Uptake but not degradation could be inhibited by heparin. CONCLUSIONS: HPMCs are distinguished by a rapid turnover of decorin. A characteristic metabolic feature is the existence of a large intracellular pool of protein-free DS-GAGs. Understanding the control of decorin turnover in HPMCs might lead to delineation of its potential role in both the physiology and pathophysiology of the membrane in PD patients. 相似文献
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Several likely precursors of schizophrenia have been identified. These range from possibly causative features, such as exposure
to perinatal insults, to features that are the effects of an underlying vulnerability, such as abnormal childhood behaviors.
Unfortunately none of these precursors is specific enough to be used in identifying individuals for targeted preventive treatment.
A more useful strategy is to combine risk factors for psychotic disorders in a population seeking help for psychiatric problems.
Thus, individuals who are possibly prodromal are identified. Research into this group has found high rates of onset of psychotic
disorders, particularly schizophrenia, within a short time frame. Preliminary treatment trials suggest that symptoms can be
reduced and psychosis onset possibly delayed or averted. 相似文献
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6.
Membrane attachment activates dnaA protein, the initiation protein of chromosome replication in Escherichia coli. 总被引:15,自引:2,他引:13 下载免费PDF全文
B Y Yung A Kornberg 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(19):7202-7205
ADP and ATP are tightly bound to dnaA protein and are crucial to its function in DNA replication; the exchange of these nucleotides is effected specifically by the acidic phospholipids (cardiolipin and phosphatidylglycerol) present in Escherichia coli membranes [Sekimizu, K. & Kornberg, A. (1988) J. Biol. Chem. 263, 7131-7135]. We now find that phospholipids derived from membranes lacking an unsaturated fatty acid (e.g., oleic acid) are unable to promote the exchange. This observation correlates strikingly with the long-known effect of 3-decynoyl-N-acetylcysteamine, a "suicide analog" that prevents initiation of a cycle of replication in E. coli by inhibiting the synthesis of oleic acid, an inhibition that can be overcome by providing the cells with oleic acid. Profound influences on the specific binding of dnaA protein to phospholipids by temperature, the content of unsaturated fatty acids, and the inclusion of cholesterol can be explained by the need for the phospholipids to be in fluid-phase vesicles. These findings suggest that membrane attachment of dnaA protein is vital for its function in the initiation of chromosome replication in E. coli. 相似文献
7.
Füst G Arason GJ Kramer J Szalai C Duba J Yang Y Chung EK Zhou B Blanchong CA Lokki ML Bödvarsson S Prohászka Z Karádi I Vatay A Kovács M Romics L Thorgeirsson G Yu CY 《International immunology》2004,16(10):1507-1514
The genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to <0.001). This haplotype is characterized by the presence of C4A null alleles and a solitary short C4B gene linked to the TNF2 allele of the promoter for TNFA gene. This haplotype occurred more frequently in the ever smokers than in the never smokers [odds ratio: 4.97 (1.96-12.62); P = 0.001], and such associations were stronger in women (odds ratio = 13.6) than in men (odds ratio = 2.79). An independent study of complement C4 protein polymorphism and smoking habits in Icelandic subjects (n = 351) yielded similar and confirmative results. Considering the documented link between olfactory stimuli and smoking in females, and the presence of a cluster of odorant receptor genes close to the MHC class I region, our findings implicate a potential role of the MHC-linked olfactory receptor genes in the initiation of smoking. 相似文献
8.
Alan Ma Sunita Gurnasinghani Edwin P. Kirk Conor McClenaghan Gautam K. Singh Dorothy K. Grange Chetan Pandit Yung Zhu Tony Roscioli George Elakis Michael Buckley Bhavesh Mehta Philip Roberts Jonathan Mervis Andrew Biggin Colin G. Nichols 《American journal of medical genetics. Part A》2019,179(8):1585-1590
Cantú syndrome (CS), characterized by hypertrichosis, distinctive facial features, and complex cardiovascular abnormalities, is caused by pathogenic variants in ABCC9 and KCNJ8 genes. These genes encode gain‐of‐function mutations in the regulatory (SUR2) and pore‐forming (Kir6.1) subunits of KATP channels, respectively, suggesting that channel‐blocking sulfonylureas could be a viable therapy. Here we report a neonate with CS, carrying a heterozygous ABCC9 variant (c.3347G>A, p.Arg1116His), born prematurely at 32 weeks gestation. Initial echocardiogram revealed a large patent ductus arteriosus (PDA), and high pulmonary pressures with enlarged right ventricle. He initially received surfactant and continuous positive airway pressure ventilation and was invasively ventilated for 4 weeks, until PDA ligation. After surgery, he still had ongoing bilevel positive airway pressure (BiPAP) requirement, but was subsequently weaned to nocturnal BiPAP. He was treated for pulmonary hypertension with Sildenafil, but failed to make further clinical improvement. A therapeutic glibenclamide trial was commenced in week 11 (initial dose of 0.05 mg–1 kg–1 day–1 in two divided doses). After 1 week of treatment, he began to tolerate time off BiPAP when awake, and edema improved. Glibenclamide was well tolerated, and the dose was slowly increased to 0.15 mg?1 kg?1day?1 over the next 12 weeks. Mild transient hypoglycemia was observed, but there was no cardiovascular dysfunction. Confirmation of therapeutic benefit will require studies of more CS patients but, based on this limited experience, consideration should be given to glibenclamide as CS therapy, although problems associated with prematurity, and complications of hypoglycemia, might limit outcome in critically ill neonates with CS. 相似文献
9.
Cells that mediate NK like cytotoxicity are present in the human delayed type hypersensitivity response. 下载免费PDF全文
D Tartof C W Yung J J Curran C Livingston Z Thalji 《Clinical and experimental immunology》1984,58(2):462-469
By inducing delayed type hypersensitivity (DTH) responses under previously formed skin blisters we determined that cells which mediate natural killer (NK) like cytotoxicity are present in the DTH response in man. Similar levels of killing were not present in cells obtained from skin blisters not associated with positive DTH responses. The DTH response associated killer cell was found to be a mononuclear cell that had presumably undergone stimulation since it not only killed NK sensitive K-562 cells, but also NK resistant Daudi target cells. 相似文献
10.
AIMS: To define epidemiology, clinical disease, and outcome of gemella bacteraemia by 16S rRNA gene sequencing. To examine the usefulness of the Vitek, API, and ATB systems in identifying two gemella species. METHODS: All alpha haemolytic streptococci other than Streptococcus pneumoniae isolated from blood cultures during a six year period were identified by conventional biochemical methods, the Vitek system, and the API system. 16S rRNA gene sequencing was performed on all isolates identified by both kits as gemella with >or= 95% confidence or by either kit as any bacterial species with < 95% confidence. The ATB expression system was used to identify the two isolates that were defined as gemella species by 16S rRNA gene sequencing. RESULTS: Of the 302 alpha haemolytic streptococci other than S pneumoniae isolated, one was identified as Gemella morbillorum, and another as Gemella haemolysans by 16S rRNA gene sequencing. The patient with monomicrobial G morbillorum bacteraemia was a 66 year old man with community acquired infective endocarditis with septic thromboemboli. The patient with G haemolysans bacteraemia was a 41 year old woman with hospital acquired polymicrobial bacteraemia during the neutropenic period of an autologous bone marrow transplant for non-Hodgkin's lymphoma, the first case of its kind in the English literature. The API and ATB expression systems only identified the second strain as G haemolysans at 94% and 99% confidence, respectively, whereas the Vitek system identified none of the two strains correctly at > 70% confidence. CONCLUSIONS: Gemella bacteraemia is uncommon. 16S rRNA gene sequencing is the method of choice for identification of gemella and gemella-like isolates. 相似文献