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71.
JD Gilbert TF Greber JD Ellis A Barrish TV Olah C Fernández-Metzler AS Yuan CJ Burke 《Canadian Metallurgical Quarterly》1995,13(8):937-950
An analytical method based on radioimmunoassay (RIA) has been developed for the determination of the antiarrhythmic agent, MK-0499, in plasma and urine. Owing to the potency of the drug, the specificity of this assay in human plasma could not be adequately determined using conventional RIA procedures. A highly specific procedure, based on LC/MS-MS, was developed to cross-validate the RIA. The lower quantifiable limits of the RIA and LC/MS-MS-based methods were 0.05 and 0.013 ng ml-1, respectively. Cross-validation data, compared using paired student's t-test regression analysis, showed excellent correlation between methods. The mass spectrometric assay was also used to simultaneously measure plasma concentrations of unlabeled and 14C-labeled MK-0499 following administration of the drug at high specific activity to volunteers. 相似文献
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Past analysis of dysbaric-induced cerebral perfusion defects, demonstrated by 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) single photon emission tomography in divers using quantitative and/or univariate techniques, has resulted i considerable controversy regarding the significance of these lesions compared to those seen in control subjects, correlations with clinical findings and the role of 99Tcm-HMPAO as a prognostic indicator in decompression sickness. We tried to address these problems by using a multivariate approach to a voxel-by-voxel analysis, involving the use of principal components, to determine ranges of normality in 50 reference controls. In subsequent images, abnormality was defined as 10 spatially connected voxels at an appropriate significance level of three standard deviations. The images of 50 divers with clinically diagnosed 'bends' were compared with those of a further 40 normal population controls with no previous history of loss of consciousness, head injury or dysbarism. The results showed that 19 of 50 divers with 'bends' and 3 of 40 population controls had significant perfusion defects, representing a significant difference between divers with dysbarism and population controls at the level P < 0.002. It is concluded that dysbarism causes significant cerebral cortical perfusion defects in affected divers both in 'silent' and symptomatic (clinically correlated) areas. 相似文献
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Pathfinding mechanisms underlying retinal ganglion cell (RGC) axon growth from the optic chiasm into the optic tract are unknown. Previous work has shown that mouse embryos deficient in GAP-43 have an enlarged optic chiasm within which RGC axons were reportedly stalled. Here we have found that the enlarged chiasm of GAP-43 null mouse embryos appears subsequent to a failure of the earliest RGC axons to progress laterally through the chiasm-tract transition zone to form the optic tract. Previous work has shown that ventral diencephalon CD44/stage-specific embryonic antigen (SSEA) neurons provide guidance information for RGC axons during chiasm formation. Here we found that in the chiasm-tract transition zone, axons of CD44/SSEA neurons precede RGC axons into the lateral diencephalic wall and like RGC axons also express GAP-43. However unlike RGC axons, CD44/SSEA axon trajectories are unaffected in GAP-43 null embryos, indicating that GAP-43-dependent guidance at this site is RGC axon specific or occurs only at specific developmental times. To determine whether the phenotype results from loss of GAP-43 in RGCs or in diencephalon components such as CD44/SSEA axons, wild-type, heterozygous, or homozygous GAP-43 null donor retinal tissues were grafted onto host diencephalons of all three genotypes, and graft axon growth into the optic tract region was assessed. Results show that optic tract development requires cell autonomous GAP-43 function in RGC axons and not in cellular elements of the ventral diencephalon or transition zone. 相似文献
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C Bais B Santomasso O Coso L Arvanitakis EG Raaka JS Gutkind AS Asch E Cesarman MC Gershengorn EA Mesri MC Gerhengorn 《Canadian Metallurgical Quarterly》1998,391(6662):86-89
The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a gamma-2 herpesvirus that is implicated in the pathogenesis of Kaposi's sarcoma and of primary effusion B-cell lymphomas (PELs). KSHV infects malignant and progenitor cells of Kaposi's sarcoma and PEL, it encodes putative oncogenes and genes that may cause Kaposi's sarcoma pathogenesis by stimulating angiogenesis. The G-protein-coupled receptor encoded by an open reading frame (ORF 74) of KSHV is expressed in Kaposi's sarcoma lesions and in PEL and stimulates signalling pathways linked to cell proliferation in a constitutive (agonist-independent) way. Here we show that signalling by this KSHV G-protein-coupled receptor leads to cell transformation and tumorigenicity, and induces a switch to an angiogenic phenotype mediated by vascular endothelial growth factor, an angiogenesis and Kaposi's-spindle-cell growth factor. We find that this receptor can activate two protein kinases, JNK/SAPK and p38MAPK, by triggering signalling cascades like those induced by inflammatory cytokines that are angiogenesis activators and mitogens for Kaposi's sarcoma cells and B cells. We conclude that the KSHV G-protein-coupled receptor is a viral oncogene that can exploit cell signalling pathways to induce transformation and angiogenesis in KSHV-mediated oncogenesis. 相似文献
79.
AS Lages KC Silva AL Miranda CA Fraga EJ Barreiro 《Canadian Metallurgical Quarterly》1998,8(2):183-188
OBJECTIVE: To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma. DESIGN: A randomized controlled trial. SETTING: A tertiary referral center. PATIENTS: During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months. INTERVENTION: Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m2 each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment. MAIN OUTCOME MEASURES: Recurrence rate and disease-free survival. RESULTS: A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20%) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P=.01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P=.03). The respective disease-free survival rates at 1, 2, and 3 years were 50%,36%, and 18% for the treatment group and 69%, 53%, and 48% for the control group (P=.04). CONCLUSION: In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome. 相似文献
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