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Biomedical subjects

C Kao

Publications and source records attributed to C Kao.

At least 73 records · Page 4Linked to original sources
PubMed1993

A molecular genetic model of human bladder carcinogenesis.

Human bladder carcinogenesis stands as a paradigm for research on the molecular genetic mechanisms of chemical carcinogenesis. The pathogenesis of bladder cancer is multistage with a typical onset later in life. Epidemiological studies associate occupational exposure to aromatic amines with increased bladder cancer risk. Biochemical studies show aromatic amine metabolism, covalent binding, and DNA adduct formation in human uroepithelial cells (HUC). Smoking increases bladder cancer risk. A possible link with certain strains of human papilloma virus (HPV) infection has recently been suggested. Molecular analyses of bladder cancers reveal multiple genetic alterations, including mutational activation of oncogenes and inactivation of suppressor genes. A working hypothesis proposes that bladder carcinogens cause mutations in cancer genes (oncogenes and suppressor genes) in HUC that, possibly together with HPV infection and viral DNA integration, lead to the development of bladder cancer. In this review, we describe how this model is currently being tested using a multistep HUC in vitro transformation system.

Female↗
PubMed1992

Nosocomial pneumonia in patients having bone marrow transplant. Attributable mortality and risk factors.

The authors performed a matched historic cohort study to determine the attributable mortality and risk factors for nosocomial pneumonia in bone marrow transplant (BMT) recipients. All patients with nosocomial pneumonia at a university tertiary care center were identified by a prospective surveillance system between 1980 and 1988. Control patients were selected from the population of BMT patients. The crude mortality for 55 patients with nosocomial pneumonia was 74.5% (95% confidence interval [CI95], 63% to 86%). The excess or attributable mortality was 61.8% (CI95, 43.7% to 80%). Aspergillus species represented the most frequent etiologic agent in this series, causing 20 of the 55 (36%) episodes. The attributable mortality of Aspergillus species pneumonia alone was 85% (CI95, 58.6% to 100%). For death in the hospital, the risk ratio for all 55 case patients relative to control patients was 9.5 (CI95, 4.1 to 22.1). To evaluate several risk factors simultaneously, a multiple logistic regression analysis using a conditional likelihood method was performed. A mathematical model with three variables best predicted nosocomial pneumonia in our patients: the occurrence of other nosocomial infections before the diagnosis of pneumonia, allogeneic BMT, and the use of methotrexate. The presence of other nosocomial infections before the diagnosis of pneumonia remained a significant independent risk factor, with an odds ratio of 13.27 (CI95, 2.51 to 70.2) after adjustment for the use of methotrexate and allogeneic BMT. Most importantly, effective methods for preventing nosocomial pneumonias in BMT recipients will have an enormous effect on crude mortality.

Bone Marrow Transplantation↗
PubMed1992

Losses of 3p, 11p, and 13q in EJ/ras-transformable simian virus 40-immortalized human uroepithelial cells.

Five independent clones of Simian virus 40 (SV40)-immortalized human uroepithelial cells (CK/SV-HUC) were established after transfection of HUC cultures from the same tissue donor with plasmids encoding SV40 large T and small t antigen genes. Each CK/SV-HUC clone contained a unique SV40 integration site, and all expressed similar levels of SV40 mRNA. All five clones were nontumorigenic, but clones 2, 4, and 5 tumorigenically transformed after transfection at P19 with mutant EJ/ras and also spontaneously after 40 serial passages in vitro. In contrast, CK/SV-HUC clones 1 and 3 did not transform when either approach was used. These differences in transformability among CK/SV-HUC clones could not be predicted based on differences in SV40 gene expression nor on any in vitro growth property tested. In cytogenetic analyses, a transformable clone showed losses of three chromosome arms containing putative cancer suppressor gene regions, including 3p14----pter, 13q, and 11p, whereas the nontransformable clones showed none of these losses. Thus these data indicate that genetic losses on 3p, 11p, and 13q may contribute to tumorigenic transformation of SV40-immortalized human uroepithelial cells.

Cell Division↗
PubMed1992

Chromosome losses in tumorigenic revertants of EJ/ras-expressing somatic cell hybrids.

Tumorigenic transformation of SV40-immortalized human uroepithelial cells (SV-HUC) after transfection with EJ/ras was previously reported to be a rare event. To test the hypothesis that ras transformation requires loss of suppressor genes, somatic cell hybrids were generated between a rare tumorigenic transformant and an isogeneic nontumorigenic EJ/ras transfectant obtained in the same experiment. Both parental cell lines, as well as all hybrid progeny, expressed mutant p21 ras protein, but injections of three such independent hybrids into athymic nude mice at passage (P) 4 demonstrated that tumorigenicity was suppressed at 20 of 22 sites. Two tumors developed, after a relatively long 17-week latent period, as compared with a 4-week latent period for the tumorigenic parent. All three hybrids produced tumors at P8, but these showed different latent periods (3-14 weeks). Revertant hybrid tumors were high-grade carcinomas. Cell lines derived from these tumors expressed mutant p21 ras and retained at least 1 EJ/ras integration site. Karyotypic analysis of six independent hybrid tumor revertants showed that each had a unique clonal karyotype. Losses of two or more homologues of 1p, 3p, 4, 8, 10p, 11p, 13q, and 18 were identified in one or more tumorigenic revertants. Losses of all these chromosomes were previously associated with transformation of SV-HUC by EJ/ras, but were also associated with chemical transformation of SV-HUC in tumors that did not express mutant ras. Genetic losses involving most of these chromosomes have also been identified in clinical bladder cancers (i.e., 1p, 3p, 8, 11p, 13 and 18q). These data show that expression of EJ/ras does not negate or significantly alter requirements for multiple genetic losses in HUC tumorigenesis.

Animals↗
PubMed1992

Different neuroendocrine systems modulate pulsatile luteinizing hormone secretion in photosuppressed and photorefractory ewes.

The objective of this study was to determine whether two photoperiod regimens that induce anestrus in the ewe-short-day photorefractoriness (SDPR) and long-day photosuppression (LDPS)--act by different neuronal mechanisms. In separate experiments, ovary-intact (INTACT), ovariectomized (OVX), and ovariectomized estradiol-treated (OVX + E) ewes were subjected to three different photoperiodic regimens that resulted in reproductive quiescence: (1) exposure to long days (16L:8D), which caused photosuppression (INTACT, n = 9; OVX, n = 6; OVX + E, n = 5; (2) prolonged exposure to short days (10L:14D)), which caused photorefractoriness (INTACT, n = 10; OVX, n = 6; OVX + E, n = 5); (3) exposure to natural photoperiod, which induced seasonal anestrus (INTACT, n = 11; OVX, n = 6; OVX + E, n = 5). Effect of photoregimen was monitored by measuring progesterone or LH. Drug challenges were made after two sequential estrous cycles were missed in INTACT ewes, after mean LH concentrations dropped below 1 ng/ml in OVX + E ewes, and after LH interpulse intervals increased in OVX ewes. Effects of drug on LH pulse pattern were determined by taking blood samples at 12-min intervals for 8 h after i.v. diluent injection; then for 8 h after i.v. injection of cyproheptadine, a serotonin antagonist (3 mg/kg); and again 7 days later after i.v. injection of diluent or pimozide, a dopamine antagonist (0.25 mg/kg). Cyproheptadine had little effect except to decrease (p = 0.05) mean LH in INTACT anestrous ewes and decrease (p less than 0.01) pulse amplitude in OVX + E SDPR ewes. Pimozide did not affect LH pulse frequency in LDPS ewes. However, pimozide increased LH pulse frequency (p less than 0.005) and mean concentrations (p less than 0.005) in SDPR OVX + E ewes, whereas it suppressed LH pulse frequency (p less than 0.05) and amplitude (p less than 0.03) in SDPR INTACT and SDPR OVX ewes. The results suggest that (1) the role of the dopaminergic system differs in SDPR and LDPS ewes, and that different neuronal systems may effect SDPR and LDPS, (2) the effect of pimozide in SDPR ewes is altered by ovarian steroids, and (3) the serotonergic system has relatively little role in regulating pulsatile LH secretion in any of the three different states of anestrus.

Animals↗
PubMed1990

A site in the T4 bacteriophage major head protein gene that can promote the inhibition of all translation in Escherichia coli.

The cryptic DNA element, e14, synthesizes a protein, Lit, which can inhibit gene expression late in T4 bacteriophage development. This inhibition is due to the interaction between the Lit protein and a short region, the gol region, within gene 23, the major head protein gene of phage T4. We have constructed plasmids in which the gol region is transcribed from the lac promoter and fused translationally and transcriptionally to lacZ and cat (chloramphenicol acetyltransferase). These fusion plasmids were used to demonstrate that, in the presence of Lit protein, the gol region inhibits the expression of genes downstream in the same transcription unit. This local inhibition does not require the gene 23 polypeptide from the gol region. In addition, inducing the transcription and translation of the gol region in the presence of Lit protein causes an immediate global inhibition of all translation in Escherichia coli. This global inhibition does require the gene 23 polypeptide. No more than 75 base-pairs of DNA from the gol region are required for both the local and global inhibitions. The gol region sequence contains a short dyad symmetry. However, it is the sequence of bases in the region of dyad symmetry and not the ability to form a hairpin in the RNA that is required for gol region activity.

Amino Acid Sequence↗
PubMed1990

Continuous exposure of Suffolk ewes to an equatorial photoperiod disrupts expression of the annual breeding season.

The objective was to determine if "clamping" ewes onto a 12L:12D photoperiod resulted in expression of circannual rhythms of reproductive activity. On 24 February, 1986, two groups of 6 yearling ewes each were placed in isolated adjacent photochambers under a 12L:12D photoperiod and controlled temperature. Six control ewes were kept outdoors. Blood samples taken thrice weekly were analyzed for progesterone. Data from Days 0-1056 are reported. The mean number of cycles by control and 12L:12D ewes did not differ (32.8 +/- 1.7 vs. 29.7 +/- 4.0). The ranges were 27-39 vs. 4-51, respectively. Ten 12L:12D ewes started cycling coincidentally or later than the controls, and then cycled either regularly or irregularly throughout the study. Two of the 12L:12D ewes cycled continuously. The mean number of cycles during the period 15 April-15 August (anestrus) in Years 1, 2, and 3 were 0.7, 0.7, 0.2 for controls versus 0.3, 5.1, and 4.5 for 12L:12D ewes. The mean number of cycles during the period 15 September-15 January (breeding season) in Years 1, 2, and 3 were 7.3, 7.7, and 7.3 for controls versus 2.8, 4.8, and 4.0 for 12L:12D ewes. All controls showed distinct, alternating annual periods of anestrus and ovarian cycles whereas only two 12L:12D ewes showed a similar pattern. Estrous cycles were distributed nonrandomly in all controls and in 2 ewes exposed to 12L:12D. In the 12L:12D ewes, melatonin concentrations rose immediately after the lights-off and fell immediately after on. Lengths of the luteal phases of the cycles did not differ between groups. In summary, estrous cycles of most ewes clamped on a 12L:12D photoperiod occurred throughout the year at variable intervals rather than in distinct breeding seasons.

Anestrus↗