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N-Acetyl-leukotriene E4 has been identified as an endogenous, biologically less active cysteinyl leukotriene metabolite in rodents and humans. To evaluate the ratio of hepatobiliary to renal elimination of leukotrienes noninvasively by positron emission tomography (PET), we synthesized N-[11C]acetyl-leukotriene E4 by chemical N-acetylation of leukotriene E4. After the intravenous injection of N-[11C]acetyl-leukotriene E4 in normal rats and monkey, uptake by the liver and subsequent excretion into bile were largely responsible for its rapid elimination from blood. In the Cynomolgus monkey, renal excretion of the leukotriene into urine was of additional quantitative importance. Kinetic modeling indicated a mean transit time through the liver of 17 minutes and 34 minutes in rat and monkey, respectively; the corresponding hepatic excretion half-times amounted to 8.5 minutes and 16 minutes. In a mutant rat strain deficient in the hepatobiliary excretion of cysteinyl leukotrienes across the canalicular membrane, the apparent mean liver transit time was 54 minutes, and the hepatic excretion half-time was 29 minutes, indicating prolonged organ storage and metabolism. After transport from the liver back into the circulating blood of omega-oxidized and beta-oxidized metabolites of N-[11C]acetyl-leukotriene E4, renal excretion compensated for the impairment of hepatobiliary elimination in the transport mutant. Metabolite analyses in urine after intravenous injection of N-[3H]acetyl-leukotriene E4 indicated the extensive inactivation of N-acetyl-leukotriene E4 by beta-oxidation from the omega-end in the mutants. A similar shift from hepatobiliary to renal cysteinyl leukotriene elimination was monitored in rats with cholestasis due to bile duct obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
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Aliquots of serum collected in a large case-control study of cervical cancer were stored at −70°C for up to 4 years during implementation of the study. When 500 μL serum aliquots were thawed in preparation for carotenoid and vitamin A assays, volumes were noticeably variable and fell below 500 μL in the majority of the samples. We were concerned about evaporation/sublimation during storage of the samples because loss of water would concentrate the analytes of interest. We evaluated the use of density and sodium ion concentration measurements to confirm its occurrence. We found that serum density was an unreliable indicator of extent of volume loss since the anticipated increases in density due to evaporation were of the same magnitude as inter-individual variation in serum density. In contrast, Na+ concentration is tightly regulated and would rise if water had been lost from the samples. In a representative sample of serum aliquots from the case-control study, 24 of 25 vials contained less than 500 μL of serum. The mean sodium ion concentration (138.1 ± 3.6 mmol/L) was within the normal range for human serum of 136–145 mmol/L, and no correlation was observed between serum volume and Na+ concentration. These results strongly suggest that the observed low volumes were not due to evaporative losses. Instead, the variably low volumes of serum aliquots were probably due to pipetting errors in the initial aliquotting resulting from the use of air-displacement pipettes.  相似文献   
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To evaluate the diagnostic validity of new assays for bone-specific alkaline phosphatase (BAP), we compared measurements of total alkaline phosphatase (TAP) in serum with results for three different assays of serum BAP in healthy adults (n = 119), patients with chronic nonskeletal disorders (n = 123), and patients with metabolic bone diseases (n = 113). Serum TAP was determined by a standard colorimetric assay, BAP by the methods of lectin precipitation (L-BAP), enzyme immunoassay (E-BAP), and immunoradiometric assay (I-BAP). Impairment of liver function resulted in significant increases of all alkaline phosphatase (AP) measurements, with the smallest changes being exhibited by E-BAP. Compared with the results by TAP, diagnostic sensitivity (i.e., of values exceeding the reference interval) was not improved by BAP, but receiver-operating characteristic (ROC) curve analyses revealed improved discrimination for primary hyperparathyroidism by E-BAP. These results indicate that, in the presence of liver disease, the specificity of AP measurements is improved by measuring BAP. In most other clinical situations, serum TAP appears to provide sufficient clinical information; however, the cross-sectional study design used here allows no statement about the usefulness of BAP in serial measurements.  相似文献   
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Children with severe combined immunodeficiency (SCID) have profoundly diminished humoral and cellular immunity resulting in death during infancy unless immune reconstitution occurs by bone marrow transplantation (BMT). Thrombocytopenia post-bone marrow transplantation can be seen in relation to infection, graft-versus-host disease (GVHD) and rarely, as an autoimmune phenomenon due to immune dysregulation. We report two cases of severe AITP following BMT for SCID. Both cases developed large intracerebral hemorrhages from which one died. Autoimmune thrombocytopenia in this setting can be life-threatening and we recommend early and active intervention.  相似文献   
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A detailed long range restriction map of the region defined by markers D6S149 and D6S193 on chromosome 6q27 has been constructed. This was achieved by YAC cloning and contig assembling of the same region. Seven YAC clones were found to span the almost 1000 Kb region flanked by the two markers which on the genetic map resulted to be 1.9 cM apart. With some of the characterized YAC clones we undertook a molecular cytogenetic analysis of 20 benign ovarian tumors. The rationale for this was the recent mapping to a region of chromosome 6q27, flanked by markers D6281 and D6S133, of a locus for the SV40-mediated immortalization of human cells (SEN6 gene). Noteworthy we found that the the D6S149-D6S193 region (comprised in the larger D6S281-D6S133 physical interval) was altered in all samples analysed adding support to the occurrence of a immortalization step in this type of tumors.  相似文献   
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This study presents a new, simple and robust, pneumatically actuated method for the generation of liquid metal micro droplets in the nano- to picoliter range. The so-called StarJet dispenser utilizes a star-shaped nozzle geometry that stabilizes liquid plugs in its center by means of capillary forces. Single droplets of the liquid metal can be pneumatically generated by the interaction of the sheathing gas flow in the outer grooves of the nozzle and the liquid metal. For experimental validation, a print head was build consisting of silicon chips with a star-shaped nozzle geometry and a heated actuator (up to 280°C). The silicon chips are fabricated by Deep Reactive Ion Etching (DRIE). Chip designs with different star-shaped geometries were able to generate droplets with diameters in the range of the corresponding nozzle diameters. The StarJet can be operated in two modes: Either continuous droplet dispensing mode or drop on demand (DoD) mode. The continuous droplet generation mode for a nozzle with 183?μm diameter shows tear-off frequencies between 25 and 120?Hz, while droplet diameters remain constant at 210?μm for each pressure level. Metal columns were printed with a thickness of 0.5–1.0?mm and 30?mm height (aspect ratio >30), to demonstrate the directional stability of droplet ejection and its potential as a suitable tool for direct prototyping of the metal microstructures.  相似文献   
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The Swedish approach to research and development in fire protection  相似文献   
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