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11.
We compared the biological activity of a new group of keto-C-glycosides to that of a narrow spectrum of unsaturated ketonucleosides in a panel of non-small-cell lung cancer (NSCLC) cells with various levels of intrinsic resistance to standard chemotherapy drugs. Unlike cisplatin, etoposide, adriamycin, or taxol, for which a significant difference in the cytotoxic effect was observed between sensitive cell lines (H460, H125, and MGH4) and drug-resistant cell lines (H661, MGH7, and FADU), nucleoside analogs were equally cytotoxic in NSCLC cell lines, with compound 92 being 10-fold more active than compound 43, 44, 81, or 161, while compound 3 was the least active. Apoptotic measurements with flow cytometric analysis of terminal uridine deoxynucleotide nick end-labeled cells revealed that the cytotoxic activity of these nucleosides correlated with their potency to induce apoptosis. Compound 92 triggered death in cells with wild-type p53, mutated p53, or p53 gene deletion. Our findings suggest that keto-C-glycosides may be promising alternative anticancer agents which merit further studies in in vivo cancer models refractory to standard chemotherapy drugs.  相似文献   
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BACKGROUND: A low-flow situation in arterial and venous grafts has been associated with high rates of perioperative infarction and mortality. This study was designed to look at intraoperative graft flow and resistance in patients with coronary artery disease. METHODS: Coronary artery bypass graft flow was measured in 46 patients. Transit-time flow was used for coronary flow measurements at rest as well as after maximal vasodilation with adenosine infusion. RESULTS: Forty-three of the 46 patients showed normal internal mammary artery graft flow (>20 mL/min); 3 patients had no or minimal graft flow. Redoing the graft anastomosis in these 3 patients resulted in normalization of graft flow. The mean flow increased significantly after correction from 0.5 +/- 0.7 mL/min to 15.7 +/- 9.6 mL/min (p < 0.02). Conversely, vascular resistance decreased significantly from 138 +/- 10 to 4.8 +/- 1.8 Ohmv (p < 0.0001), as did the pulsatility index (from 146.9 +/- 95.7 to 3.4 +/- 1.8; p < 0.001). After correction, coronary flow reserve was 2.5 +/- 1.1. CONCLUSIONS: Measurements of intraoperative flow and resistance as well as derived variables allow assessment of early graft function and thus help prevent graft failure and reduce perioperative infarction. Transit-time volume flow might be a simple tool for quality control in coronary bypass procedures.  相似文献   
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The authors propose a comprehensive approach to laboratory diagnosis of seasonal transmissible infections, based on modern methods permitting etiological deciphering of disease. A universal diagnostic algorithm notably accelerated the laboratory diagnosis due to cutting the period between collection of material from a patient and consecutive screening for antibodies to agents of tick-borne encephalitis, Lyme disease, and California encephalitis.  相似文献   
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The Escherichia coli Fpg protein is involved in the repair of oxidized residues. We examined, by targeted mutagenesis, the effect of the conserved lysine residue at position 57 upon the various catalytic activities of the Fpg protein. Mutant Fpg protein with Lys-57-->Gly (K57G) had dramatically reduced DNA glycosylase activity for the excision of 7,8-dihydro-8-oxo-guanine (8-oxoG). While wild type Fpg protein cleaved 8-oxoG/C DNA with a specificity constant ( k cat/ K M) of 0.11/(nM@min), K57G cleaved the same DNA 55-fold less efficiently. FpgK57G was poorly effective in the formation of Schiff base complex with 8-oxoG/C DNA. The efficiency in the binding of 8-oxoG/C DNA duplex for K57G mutant was decreased 16-fold. The substitution of Lys-57 for another basic amino acid Arg (K57R) had a slight effect on the 8-oxoG-DNA glycosylase activity and Schiff base formation. The DNA glycosylase activities of FpgK57G and FpgK57R using 2,6-diamino-4-hydroxy-5N-methylformamidopyrimidine residues as substrate were comparable to that of wild type Fpg. In vivo, the mutant K57G, in contrast to the mutant K57R and wild type Fpg, only partially restored the ability to prevent spontaneously induced transitions G/C-->T/A in E.coli BH990 ( fpg mutY ) cells. These results suggest an important role for Lys-57 in the 8-oxoG-DNA glycosylase activity of the Fpg protein in vitro and in vivo.  相似文献   
15.
We systematically examined relations among 6 measures of child language derived from 3 sources, including observations of the child's speech with mother, experimenter assessments, and maternal reports. A total of 184 20-month-olds and their mothers contributed complete information about child language comprehension and expression. Correlations of child language measures with socioeconomic status and maternal education were accounted for, as were correlations of child language measures with mothers' verbal intelligence, maternal report measures with mothers' tendency to respond in a socially desirable fashion, and experimenter assessments with child social competence. Structural equation modeling supported (1) strong relations among child language measures derived from observations of the child's speech with mother, experimenter assessments, and maternal reports; (2) the loading of multiple measures of child language from different sources on a single latent construct of vocabulary competence; and (3) the predictive validity of the vocabulary competence latent variable at 20 months, as well as receptive vocabulary specifically, for both verbal and performance IQ (verbal better than performance) at 48 months. Neither an index of child monologing (a nonvocabulary language measure) nor symbolic play (a nonlinguistic representational measure) covaried with vocabulary competence. Girls consistently outperformed boys on individual language measures, but no differences emerged in any model in the fit for boys and girls.  相似文献   
16.
We report construction and characterization of tetracycline-controlled hepatitis B virus pX-expressing hepatocyte (AML12) cell lines. These cell lines were constructed in AML12 clonal isolates (clones 3 and 4), which express constitutively the tetracycline-controlled transactivator. Since pX is implicated in HCC, this immortalized hepatocyte model system was used to investigate the mechanism of pX in transformation. Clonal isolates of 3pX and 4pX lineages display conditional synthesis of pX mRNA and protein and a 2-fold increase in growth saturation density following tetracycline removal, implicating pX in monolayer overgrowth. Interestingly, only 3pX clones display pX-dependent anchorage independence. Clone 3 lineages express hepatocyte nuclear factor-1alpha and hepatocyte-specific marker genes; clone 4 lineages express hepatocyte nuclear factor-1beta and reduced levels of hepatocyte-specific marker genes, suggesting the importance of the differentiated hepatocyte in pX-mediated oncogenic transformation. Importantly, 3pX and 4pX lineages display differential expression of immediate early genes c-fos and ATF3. The pX-transforming 3pX lineage displays early, pX-dependent induction of ATF3 and prolonged induction of c-fos. The nontransforming 4pX cells display an absence of pX-dependent ATF3 induction and transient induction of c-fos. Our results support the direct link of pX expression to oncogenic transformation in 3pX lineage clones and underscore the advantage of this conditional cellular model system for studying mechanisms of pX-mediated oncogenesis.  相似文献   
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The authors report the case of a chronic myeloid leukemia (CML) patient submitted to allogenic bone marrow transplantation, who had probably never entered complete remission. The disease was reactivated as a granulocytic sarcoma, next to a platinum plate installed to correct a tibia fracture 11 years earlier. Its final event was a myeloid Ph1 + blastic crisis that was unsuccessfully treated with high doses of sc interferon and citarabine.  相似文献   
20.
BACKGROUND: The distinction between malignant mesothelioma (MM) and adenocarcinoma (ACA) in cytologic specimens frequently is difficult, often requiring immunocytochemistry to support the diagnosis. Recent reports have proposed the utilization of antibodies to mesothelial cell clone HBME-1 and thrombomodulin (TM), because they are immunoreactive in MM and less commonly reactive in ACA. Immunoreactivity for the monoclonal antibody CA 19-9 has been observed in many ACAs and reportedly is absent in MM. METHODS: In this study, immunostaining was performed on formalin fixed, paraffin embedded cell blocks from effusions or fine-needle aspirations using the avidin-biotin-peroxidase method. Thirty-eight MMs and 49 ACAs were tested using antibodies to CA 19-9, HBME-1, and TM. RESULTS: Anti-CA 19-9 stained only 1 of the 37 cases of MM tested (3%), but stained 24 of the 49 cases of ACA (49%). Anti-HBME-1 stained 34 of 38 cases of MM (89%), and 28 of 43 cases of ACA tested (65%). Anti-TM stained 24 of 36 cases of MM (67%), and 21 of 40 cases of ACA tested (53%). CONCLUSIONS: CA 19-9 has utility as part of an immunocytochemical panel for distinguishing ACA from MM, because a positive staining reaction would make the diagnosis of MM unlikely. Although HBME-1 and TM can identify MM positively, each frequently is detected in ACA, thus limiting the utility of these antibodies in cytologic specimens.  相似文献   
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