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Biomedical subjects

K Doherty

Publications and source records attributed to K Doherty.

29 records · Page 2Linked to original sources

Tobacco, alcohol, and marijuana use among black adolescents: a comparison across gender, grade, and school environment.

Self-report measures of tobacco, alcohol, and marijuana use were administered to 2,748 black adolescents, grades 7 through 12. The proportion of students who had tried any of the substances increased by grade. Males and females were not significantly different in their use of cigarettes and alcohol. Males were more likely to have tried smokeless tobacco, smoked marijuana, and used combinations of substances. Females who reported using more than one substance preferred the combination of cigarettes and alcohol. Significant effects of school environment were noted. Increasing age-related experimentation is exacerbated by school setting (junior high versus senior high). Given that blacks have disproportionately high cancer prevalence and mortality rates, intervention programs may also need to consider school environment, substance specific initiation points, and combined use preferences in order to maximize the desired effect within this population.

Adolescent↗

The in vitro proliferative response of lymphoid cells of mice infected with Salmonella enteritidis 11RX.

Intraperitoneal injection of (BALB/c x C57BL/6) F1 mice with live, but not killed Salmonella enteritidis 11RX (11RX) induced T cells in the spleen and peritoneal cavity which were able to proliferate in vitro in response to two different forms of 11RX antigens. The majority of cells which proliferated were L3T4+ T cells and most of the response was restricted by the I-A locus of the H-2 major histocompatibility complex, although a smaller K region restricted response was also detected. T cells able to respond to 11RX antigens could only be demonstrated when non-adherent lymphoid cell suspensions from immunized mice were used, and usually a limited response was obtained unless small numbers of adherent cells present in normal peritoneal cell suspensions were added. Cells cultured in vitro for 3 days were able to mediate local transfer of delayed type hypersensitivity and secondary immunization did not enhance the reactivity of responding cells to 11RX antigens.

Animals↗

Bioavailability of low-dose vs high-dose 6-mercaptopurine.

The bioavailability of oral 6-mercaptopurine (6MP) at standard doses is very low, largely as a result of extensive first-pass metabolism by xanthine oxidase. Fewer than one third of patients achieve 6MP plasma concentrations known to be cytocidal in vitro (greater than 1 mumol/L). Studies in vitro have suggested that first-pass metabolism can be saturated at higher doses of 6MP. To determine whether saturation occurs in vivo at clinically used doses and whether bioavailability can be enhanced by increasing the dose, the bioavailability of different doses of 6MP was studied first in rhesus monkeys and then in children with acute lymphoblastic leukemia in remission. In monkeys a higher dose of 6MP resulted in enhanced bioavailability, whereas in patients the mean relative bioavailability at the higher dose was significantly less. However, all patients achieved cytocidal (greater than 1 to 10 mumol/L) plasma concentrations at the higher dose without manifesting significant clinical toxicity. Therefore cytocidal levels of 6MP can be achieved in patients with oral 6MP without the risk of unexpectedly high levels caused by saturation of first-pass metabolism.

Adolescent↗

Mitral and aortic blood flows during spontaneous respiration in dogs.

Left sided hemodynamic events during respiration remain a controversial subject. Left ventricular (LV) hemodynamic events were evaluated during obstructed and partially obstructed inspiration in anesthetized dogs acutely instrumented with mitral (Qm) and ascending aortic (Qa) flow probes. This allows classification of the inspiratory decrease in LV stroke volume as either a diastolic event (e.g., ventricular interdependence) in which case the LV inflow volume (integral of Qm) should decrease before the LV outflow volume (integral of Qa), or a systolic event (e.g., afterload or contractility) in which case outflow (integral of QA) should decrease before inflow (integral of Qm). During either unobstructed (n =8) or partially obstructed (n = 5 spontaneous ventilation, Qm reached both its inspiratory minimum and expiratory maximum prior to the associated minimum and maximum values for integral of in 80% or more of the respiratory cycles. Thus, a diastolic event dominates both in reducing the subsequent LV outflow during the expiratory increase in intrathoracic pressure. However, because a diastolic event did not occur first at all times, a systolic event must occur first at all times, a systolic event must also be present. If a rapid change in intrathoracic pressure occurred during diastole, integral of Qm invariably immediately increased. If a rapid in intrathoracic pressure occurred during systole, integral of Qa could change independently of the preceding integral of Qm. Both systolic and diastolic mechanisms contribute to the inspiratory fall in LV output. These mechanisms will not be clearly delineated without evaluating the effects of intrathoracic pressure within a single cardiac cycle.

Airway Obstruction↗

Effects of changes in left ventricular loading and pleural pressure on mitral flow.

The cause of the fall in left ventricular (LV) stroke volume (SV) during a fall in pleural pressure (Pp1) has been in dispute for over a century. We have defined the changes in the temporal relationship between LV inflow (Qm) and outflow (Qa) in a canine preparation to test the mutually exclusive hypotheses that the fall in LVSV is caused only by changes during diastole (e.g., ventricular interdependence) or only by changes during systole (e.g., afterload). The ability of the experimental preparation to measure the results of acute changes in right heart volume or output and acute changes in LV afterload was validated in open-chest studies with and without pericardial constraint. In closed-chest studies, with a fall in Pp1 during a Mueller maneuver Qm reached both its inspiratory minimum and expiratory maximum before Qa in 80% of the Mueller maneuvers, invalidating both hypotheses, which each required that one flow lead the other in 100% of the Mueller maneuvers. Review of individual records suggested that if the rapid changes in Pp1 occurred during systole, Qa could vary in a manner independent of the preceding Qm. These studies suggest that both diastolic and systolic events may contribute to the fall in SV, while causing opposite changes in LV volumes.

Animals↗

Phosphorylation of a 75,000 molecular weight cytosol protein induced by platelet derived growth factor and tumor promoter in BALB/c-3T3 cells.

In order to identify common mechanisms of action by which both the platelet-derived growth factor (PDGF) and the tumor promoter tetradecanoyl phorbol acetate (TPA) initiate cell growth, the effects of PDGF and TPA on phosphorylation of cellular proteins were examined in density-inhibited Balb/c-3T3 cells. Cultures were incubated with 32Pi and growth factor, and 32P-labeled cellular proteins were examined after separation by SDS-polyacrylamide gel electrophoresis and autoradiography. TPA and PDGF each induced phosphorylation of a major cytosol protein of approximately 75,000 molecular weight (pp75). Phosphorylation of this protein was not induced by either epidermal growth factor or insulin, neither of which initiate 3T3 cell growth but enhance growth later in the 3T3 cell cycle. pp75 was a single band under reduced and non-reduced conditions, and a single spot was seen on two-dimensional gels. Phosphorylation did not occur at 4 degrees C. Phosphorylation of the protein was observed within 3 min and reached a maximum in 10-30 min. Submitogenic doses of TPA and PDGF induced submaximal phosphorylation. The phosphoprotein was labeled only on serine. Cell free phosphorylation of pp75 occurred at 4 degrees C in the presence of Mg++ and Ca2+. Homogenates from cultures pretreated with TPA phosphorylated pp75 in the presence or absence of Ca2+. Phosphorylation of this protein may possibly be related to activation of the Ca2+-dependent, phospholipid sensitive protein kinase C.

Animals↗

Social class and chronic illness in Dublin.

Information on the social class distribution of illness is scarce in Ireland. The aim of this study was to document the social class distribution of 12 common chronic conditions in middle-aged persons in Dublin. Data were collected on 3,111 individuals attending three large general practices over the course of a calendar year, and 1,024 individuals living in the same areas. Ten out of the 12 conditions studied were significantly more common in those from social classes five and six, than those from social classes one and two. Persons from social classes three and four, classes five and six, had an overall excess morbidity rate of 21% and 70% respectively. The distribution of chronic illness in middle-aged residents of Dublin is social class related.

Chronic Disease↗