CNS 7065 is a high-affinity and selective ligand for the benzodiazepine site on the GABAA receptor. CNS 7056 does not show selectivity between GABAA receptor subtypes. CNS 7056 is a potent sedative in rodents with a short duration of action. Inhibition of substantia nigra pars reticulata firing and the inhibition of the effects of CNS 7056 by flumazenil show that it acts at the brain benzodiazepine receptor.
Two ovarian cell lines were derived from the ascites of a patient before and after the onset of resistance to chemotherapy involving cis-platinum, chlorambucil and 5-fluorouracil. Characterization of these lines shows them to have various features in common and some significant differences. Cytologically the lines cannot be distinguished and they both contain high concentrations of oestrogen receptor. However, they do differ with respect to their growth characteristics, karyotype, glutathione content and sensitivity to cis-platinum. The karyotypes of the 2 lines show several marker chromosomes in common but the resistant line contained a chromosome 8 and a 17 which were absent from the earlier sensitive line. This suggests a clonal origin with subsequent divergence to a heterogeneous population.
Alginate-polylysine microencapsulation has been proposed as a method of protecting transplanted pancreatic islets against immunological attack. Using this technique, prolonged graft survival has been reported in some diabetic animals. However, in the spontaneously diabetic insulin-dependent BB/E rat we found that intraperitoneal implantation of microencapsulated islets had only a short-lived effect on hyperglycaemia. Recovered microcapsules (both those implanted empty and containing islets) were surrounded by a foreign body type cellular overgrowth and, although many capsules remained intact, encapsulated islets were observed to be disintegrating. Loss of Beta cells was confirmed by immunohistology. Various polymer materials used in artificial membranes have been shown to activate macrophages involved in foreign body reactions and induce synthesis of interleukin-1 beta, a known Beta-cell toxin. Reduced secretion of insulin and progressive islet damage (indicated by a significant reduction in residual islet insulin and DNA content) were demonstrated when microencapsulated islets were incubated with interleukin-1 beta in vitro for 9 days. Similar effects were seen following exposure to a combination of gamma interferon and alpha tumour necrosis factor. Successful use of microencapsulation in islet transplantation depends upon the development of biocompatible membranes. The exclusion of smaller molecules, such as cytokines, which may be involved in foreign body mediated damage and microencapsulated islet graft rejection, could also be important.
Signal phase variations caused by physiology are a major source of instability in fMRI images produced by multiple RF pulses. k-Space phase variation maps show cyclic phase variations at the frequency of respiration combined with a cardiac variation of lower amplitude. The amplitude of the variation increases with gradient echo time and proximity to the chest, suggesting that the dominant cause of the phase variation is a B0 shift (approximately 0.01 ppm) produced by movement of organs in the chest. A simple k-space phase correction method is proposed and demonstrated for FLASH fMRI. The retrospective method requires no pulse sequence modification, and is more effective than navigator echo correction. Physiological noise is dramatically reduced, especially at inferior slice locations.
To determine the source of a nosocomial outbreak of Legionella pneumophila serogroup 1 infection and the efficacy of control measures, clinical and environmental isolates were characterized by molecular subtyping and disease surveillance was conducted. The outbreak involved 32 cases (relative risk, 4.0; P less than .001 vs. previous period). Water colonization with L. pneumophila serogroup 1 and patients' exposure to faucet use incriminated the water system as the environmental source. Monoclonal antibody typing showed that patient isolates belonged mainly to type Pontiac and water isolates mainly to type Bellingham (P less than .001). By four genotypic techniques, outbreak-related isolates from patients and the water system were found to be clonally related and distinct from control strains (P less than .001). Heat and UV light treatment of the water system showed a protective efficacy of 88% (95% confidence interval, 75%-94%). These findings indicate that phenotypic variation may interfere with monoclonal antibody typing of legionellae and that waterborne legionellosis can be controlled by physical disinfection.
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