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Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
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TF Leung WC Tsoi CK Li KW Chik MMK Shing PMP Yuen 《Acta paediatrica (Oslo, Norway : 1992)》1998,87(6):705-777
We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients. 相似文献
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Five female patients and one male patient with solid and papillary epithelial neoplasms of the pancreas were examined with computed tomography (CT). The mean age of the patients was 27 years (range, 13-46 years). All cases showed well-encapsulated, round or lobulated masses consisting of both cystic and solid areas. Cystic portions showed CT numbers that suggested hemorrhagic necrosis. There were no internal septations within the masses. In three tumors located in the head of the pancreas, dilatation of the biliary tree was absent or minimal, although the masses were large. Two tumors contained calcifications. One tumor demonstrated metastatic deposits in liver and lymph nodes. Metastatic masses appeared similar to the primary pancreatic mass. Solid and papillary neoplasm of the pancreas should be the primary diagnostic consideration when characteristic CT findings are detected in a young female patient. 相似文献
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G V Alexeeff M J Lipsett K W Kizer 《American Industrial Hygiene Association journal》1989,50(11):598-605
The possibility of accidental industrial chemical releases has generated considerable recent attention. One area requiring research for emergency planning is the development of safe exposure concentrations for the public in the event of an inadvertent release. The United States Environmental Protection Agency (EPA) has established a list of extremely hazardous substances and suggested that the toxicity ranking for 92 hazardous materials could be based on the "immediately dangerous to life or health" (IDLH) values developed by the National Institute for Occupational Safety and Health (NIOSH) and the Occupational Safety and Health Administration (OSHA). Eighty-four compounds with IDLH values for which published toxicologic data were available were reviewed to assess the appropriateness of applying such values to accidental release situations. When compared with 30-min animal median lethal concentrations (LC50s), 18 of the IDLHs reviewed were in the same range as lethal levels for animals. For 45 compounds the IDLH values were comparable to concentrations producing severe toxic effects (specifically, unconsciousness, incapacitation, or intolerable irritation). Where available, emergency planning guidelines for the military were compared to IDLHs, and in all 31 cases, the IDLHs exceeded the military exposure guidelines. Twenty compounds also were found to pose a potential cancer risk according to common regulatory guidelines, even under the assumption of a single, 30-min exposure at the IDLH concentration. In addition, the high degree of variability (four orders of magnitude) in the relationship of IDLH values to outcomes of lethality or severe toxicity suggests that the use of IDLH values as emergency planning guidelines for accidental releases is questionable.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes 总被引:5,自引:0,他引:5
Shuber AP; Michalowsky LA; Nass GS; Skoletsky J; Hire LM; Kotsopoulos SK; Phipps MF; Barberio DM; Klinger KW 《Human molecular genetics》1997,6(3):337-347
As more mutations are identified in genes of known sequence, there is a
crucial need in the areas of medical genetics and genome analysis for
rapid, accurate and cost-effective methods of mutation detection. We have
developed a multiplex allele-specific diagnostic assay (MASDA) for analysis
of large numbers of samples (> 500) simultaneously for a large number of
known mutations (> 100) in a single assay. MASDA utilizes
oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA
samples are immobilized on a solid support and a single hybridization is
performed with a pool of allele-specific oligonucleotide (ASO) probes. Any
probes complementary to specific mutations present in a given sample are in
effect affinity purified from the pool by the target DNA. Sequence-specific
band patterns (fingerprints), generated by chemical or enzymatic sequencing
of the bound ASO(s), easily identify the specific mutation(s). Using this
design, in a single diagnostic assay, we tested samples for 66 cystic
fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell
anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations,
four mutations in Canavan disease, four mutations in Fanconi anemia, and
five mutations in BRCA1. Each mutation was correctly identified. Finally,
in a blinded study of 106 of these mutations in > 500 patients, all
mutations were properly identified. There were no false positives or false
negatives. The MASDA assay is capable of detecting point mutations as well
as small insertion or deletion mutations. This technology is amenable to
automation and is suitable for immediate utilization for high-throughput
genetic diagnostics in clinical and research laboratories.
相似文献
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A 44-year-old Caucasian female was admitted with a subarachnoid hemorrhage owing to a multilobular tubular anterior communicating artery aneurysm. Eleven days after the original craniotomy, an epidural hematoma was evacuated. The patient was placed on empiric nafcillin antimicrobial coverage (two g every six hours). Within 24 hours, the onset of epistaxis and oozing of blood from the endotracheal tube and craniotomy site was noted. Recurrent subdural and epidural hematomas necessitated a third emergent craniotomy. The development of an acquired qualitative platelet defect was suggested by the findings of a prolonged template bleeding time and markedly abnormal platelet aggregation/ATP release studies despite a normal platelet count. Nafcillin therapy was immediately discontinued. Clinical bleeding resolved. Subsequent bleeding times and platelet aggregation studies confirmed the nafcillin-induced platelet dysfunction. 相似文献