Search PubMed⌕ Search

Biomedical subjects

K O'Neill

Publications and source records attributed to K O'Neill.

70 records · Page 4Linked to original sources
PubMed1989

Dominant yeast and mammalian RAS mutants that interfere with the CDC25-dependent activation of wild-type RAS in Saccharomyces cerevisiae.

Two mutant alleles of RAS2 were discovered that dominantly interfere with wild-type RAS function in the yeast Saccharomyces cerevisiae. An amino acid substitution which caused the dominant interference was an alanine for glycine at position 22 or a proline for alanine at position 25. Analogous mutations in human H-ras also dominantly inhibited RAS function when expressed in yeast cells. The inhibitory effects of the mutant RAS2 or H-ras genes could be overcome by overexpression of CDC25, but only in the presence of wild-type RAS. These results suggest that these mutant RAS genes interfere with the normal interaction of RAS and CDC25 proteins and suggest that this interaction is direct and has evolutionarily conserved features.

Alleles↗
PubMed1989

Characterization of the ros1-gene products expressed in human glioblastoma cell lines.

Most glioblastoma-derived cell lines express an 8.3 kb ros1 transcript and a 280 kD glycoprotein designated gp280ros1, which can be specifically immunoprecipitated with an anti-ROS antibody. This 280 kD protein possesses in vitro autokinase activity and was observed in four independent glioblastoma cell lines. In a fifth glioblastoma cell line, U-118 MG, a smaller ros1 transcript of 4.0 kb was observed. Immunoprecipitation analysis reveals that the U-118 MG expressed a smaller, 116 kD ros1 gene product. cDNA cloning and sequencing of the U-118 MG ros1 transcript indicates it encodes the entire tyrosine kinase domain and two amino acids of the transmembrane domain of ros1 at its 3' end. Sequences at its 5' end likely arise from another gene.

Amino Acid Sequence↗
PubMed1988

Trial of high-dose Edmonston-Zagreb measles vaccine in the Gambia: antibody response and side-effects.

In a randomised trial, infants living in a large village in The Gambia were immunised either at 4 months of age with 40,000 plaque forming units (PFU) of the Edmonston-Zagreb (EZ) measles vaccine or at the usual age of 9 months with 6000 TCID50 of a conventional Schwarz measles vaccine. Measles developed in 2 of 119 children who received the EZ vaccine, in 1 before and in the other after 9 months of age. In the Schwarz group measles developed in 7 of 120 children--in 5 before and in 2 after 9 months of age. Serological responses measured at 5 months after vaccination and at 18 months of age were satisfactory in both groups although in the Schwarz group levels were on average 2-fold higher than in the EZ group. The frequencies of fever, cough, vomiting, and diarrhoea were no higher in the EZ vaccinees in the 3 weeks following vaccination than in age-matched non-immunised controls. Long-term morbidity as assessed by clinic attendances and weight at 18 months of age was much the same in the two groups. The EZ measles vaccine is thus safe and clinically and serologically effective when used in a high dose to immunise young Gambian infants.

Age Factors↗
PubMed1988

Effects of dose and strain of vaccine on success of measles vaccination of infants aged 4-5 months.

Small-scale trials of the Edmonston-Zagreb (E-Z) measles vaccine were undertaken to determine the dose necessary to immunise 4-6-month-old infants. Antibody responses, measured 16 weeks after vaccination, were dose dependent: 40,000 plaque forming units given subcutaneously resulted in positive responses in all infants and higher antibody levels than doses of 20,000 or 10,000 units (10,000 units gave a failure rate of 25%). In further trials the E-Z vaccine was compared with the Schwarz vaccine, both being given in subcutaneous doses of 40,000 plaque forming units. In infants aged 20 weeks the E-Z vaccine produced higher levels of measles antibody and in those aged 18 weeks its superiority showed in a lower proportion failing to respond (3 of 39 versus 19 of 35).

Clinical Trials as Topic↗
PubMed1988

Increased adherence of human granulocytes to herpes simplex virus type 1 infected endothelial cells.

We studied the interaction of human polymorphonuclear leukocytes (PMNs) with umbilical vein endothelial cells infected with herpes simplex virus (HSV) type 1. PMNs labeled with 51Cr were added to endothelial monolayers at varying times after infection and their adherence assessed 1 h later. Granulocyte adherence (GA) to uninfected cells averaged 26.5 +/- 1.9%. Increased adherence began 6 h postinfection and rose to a maximum at 20 to 24 h. HSV-1 glycoproteins seemed to mediate the increase in GA: tunicamycin treatment of infected monolayers for 18 h abolished the increased GA as did incubation of infected cells with F(ab')2 fragments prepared from human antiserum containing HSV-1 antibody.

Cell Adhesion↗
PubMed1988

Characterization of the rat mas oncogene and its high-level expression in the hippocampus and cerebral cortex of rat brain.

The human mas oncogene was originally detected by its ability to transform NIH 3T3 cells. We previously showed that the protein encoded by this gene is unique among cellular oncogene products in that it has seven hydrophobic potential transmembrane domains and shares strong sequence similarity with a family of hormone-receptor proteins. We have now cloned the rat homolog of the mas oncogene, determined its DNA sequence, and examined its expression in various rat tissues. A comparison of the predicted sequences of the rat and human mas proteins shows that they are highly conserved, except in their hydrophilic amino-terminal domains. Our examination of the expression of mas, determined by RNA-protection studies, indicates that high levels of mas RNA transcripts are present in the hippocampus and cerebral cortex of the brain, but not in other neural regions or in other tissues. This pattern of expression and the similarity of mas protein to known receptor proteins suggest that mas encodes a receptor that is involved in the normal neurophysiology and/or development of specific neural tissues.

Amino Acid Sequence↗
PubMed1986

Azacytidine induces reversion of thymidine kinase deficiency in Friend erythroleukemia cells.

Cells of the Friend erythroleukemia cell line show a high frequency of variants which have lost thymidine kinase activity. We have exposed a thymidine kinase-deficient clone of this cell line to a series of concentrations of azacytidine and found a dose-dependent induction of thymidine kinase-positive revertants. Maximum reversion occurred with 0.9 micrograms/ml azacytidine where the frequency of revertants amongst survivors was increased by a factor of 10(6) compared to that of control cultures. Revertants were found to have varying levels of thymidine kinase activity. We conclude that DNA methylation of one or both alleles of the thymidine kinase gene is largely responsible for the instability of this gene in Friend erythroleukemia cells.

Alleles↗
PubMed1986

Ethanol inhibition of granulocyte adherence.

Ethanol inhibits granulocyte adherence (GA) in whole blood. To determine the mechanism, GA was measured by the nylon fiber assay. In vitro addition of 300 mg/dl ethanol to whole blood caused a 28.1% decrease of GA compared with the control value (p less than 0.009) but did not affect GA of pure PMNs suspended in plasma or in HBSS. Similarly, GA measured in whole blood from intoxicated rabbits fell 48.8% from preintoxication values, but adherence of isolated postintoxication PMNs suspended in postintoxication plasma was not inhibited. Therefore, inhibition of GA by ethanol requires the presence of other cellular components of whole blood. To determine which cell(s) mediate the inhibition, PMNs were suspended with isolated blood components: platelet-rich and platelet-poor plasma, with and without the addition of mononuclear leukocytes and RBCs. Although the reconstitution of whole blood from its components allowed alcohol-induced inhibition of GA (decrease of 32.9%), none of the incomplete blood component mixtures demonstrated this effect. It was concluded that inhibition of GA by ethanol is mediated by an interaction between the components of whole blood.

Adult↗
PubMed1983

Effect of low-level lead exposure on antibody-dependent and natural killer cell-mediated cytotoxicity.

Splenic antibody-dependent, cell-mediated cytotoxicity against chicken red blood cell targets [ADCC (CRBC)] and natural killer cell-mediated cytotoxicity (NKMC) were determined in C57BL/6 mice given 1300 ppm lead acetate (827 ppm lead) in their drinking water for 8 weeks. ADCC in lead exposed mice was significantly lower than controls at effector to target cell ratios of 100:1, 50:1, and 25:1. In contrast, no significant difference in unstimulated NKMC was seen in lead exposed mice and control mice at effector to target cell ratios of 200:1, 100:1, and 50:1. Moreover, in vivo poly I:C-enhanced NKMC in lead-treated mice was similar to controls at an effector to target cell ratio of 200:1. Blood lead levels averaged 40.5 +/- 1.2 micrograms% in lead-exposed mice and 1.9 +/- 0.3 micrograms% in controls. These findings suggest that chronic low-level lead exposure in mice results in significant suppression of ADCC (CRBC) but does not alter natural killer activity.

Animals↗
PubMedDate not supplied

The stability of deoxynivalenol and 3-acetyl deoxynivalenol to gamma irradiation.

The stability of deoxynivalenol and 3-acetyl deoxynivalenol to irradiation by 60Co-gamma radiation under various conditions was investigated. Deoxynivalenol and 3-acetyl deoxynivalenol were irradiated on maize, in aqueous solution and in the dry state. Breakdown of the toxins was monitored by high performance liquid chromatography. Both deoxynivalenol and 3-acetyl deoxynivalenol were more sensitive to irradiation when irradiated in aqueous solution than when irradiated on maize. Breakdown of deoxynivalenol and 3-acetyl deoxynivalenol in aqueous solution began at 1 kGy and 5 kGy respectively and both toxins were completely destroyed by 50 kGy. When irradiated on maize, breakdown of the toxins only began after irradiation to 20 kGy and 80-90% of the toxins remained after irradiation to 50 kGy. Irradiation of the toxins did not cause the formation of new compounds of increased toxicity to baby hamster kidney cells. Both DON and 3-A DON were stable to irradiation to 50 kGy when irradiated in the dry condition. The use of low dose gamma irradiation to destroy preformed toxins present on grain does not appear to be a suitable method for the detoxification of grain contaminated with deoxynivalenol and 3-acetyl deoxynivalenol because of the high irradiation dose that would be required for their destruction (> 50 kGy).

Animals↗
PubMedDate not supplied

Perceived barriers to physical activity by older adults.

The purpose of this study was to investigate the perceived barriers to physical activity by older adults. 199 volunteers responded to the Perceived Barriers Questionnaire (PBQ). The subjects resided in apartment residences for independent, healthy, older adults. Older adults perceived as many as 17 barriers to physical activity. The number of barriers per subject was significantly related to age and illness or handicap. The remaining factors, gender, income, activity and educational levels, were not related to the number of barriers. There was a significant difference among four specific types of barriers (i.e. Psychological, Administrative, Physical/Health, Knowledge) with barriers of the knowledge dimension being most often identified.

Aged↗