Search PubMed⌕ Search

Biomedical subjects

C Harris

Publications and source records attributed to C Harris.

At least 217 records · Page 12Linked to original sources
PubMed1986

Rabbit pulmonary cytochrome P-450 monooxygenase system: isozyme differences in the rate and stereoselectivity of styrene oxidation.

The rate and stereoselectivity of the cytochrome P-450 (P-450)-dependent oxidation of styrene to styrene 7,8-oxide (SO) were determined in rabbit pulmonary microsomes and with purified rabbit pulmonary P-450 isozymes in reconstituted monooxygenase systems. Stereoselectivity was determined by separation of the diastereomeric SO-glutathione adducts by high-performance liquid chromatography; these four compounds accounted for more than 95% of the SO formed. Pulmonary microsomes preferentially formed (R)-SO [(R)-SO/(S)-SO = 1.6] at a rate of 7.5 nmol of SO formed/min/nmol of P-450. Antibodies to NADPH-P-450 reductase (antireductase) inhibited SO formation in pulmonary microsomes by greater than 98%. In the presence of antibodies to P-450 form 2 (anti-2), pulmonary microsomes oxidized styrene to equal amounts of (R)- and (S)-SO at a rate of 4.2 nmol of SO/min/nmol of total P-450; in the presence of antibodies to P-450 form 5 (anti-5), styrene was stereoselectively oxidized to (R)-SO [(R)-SO/(S)-SO = 2.0] at a rate of 6.5 nmol of SO/min/nmol of total P-450. In reconstituted monooxygenase systems, P-450 forms 2, 5 and 6 oxidized styrene to SO at rates of 10.0, 4.7 and 4.5 nmol of SO formed/min/nmol of P-450, respectively. The relative amounts of (R)-SO and (S)-SO produced were 2.0, 1.0 and 0.9, respectively. Predicted values for rate and stereoselectivity of styrene oxidation by pulmonary microsomes, calculated from the values obtained in the reconstitution experiments and the relative concentrations of the different P-450 isozymes, agreed well with experimentally determined values.

Animals↗
PubMed1986

A new method to study glutathione adduct formation in periportal and pericentral regions of the liver lobule by micro-reflectance spectrophotometry.

A method was developed to measure the formation of glutathione adducts of 1-chloro-2,4-dinitrobenzene (CDNB) and 2,4-dichloro-1-nitrobenzene (DCNB) in periportal and pericentral regions of the liver lobule in the isolated perfused rat liver by surface reflectance spectrophotometry. Conjugates of DCNB and CDNB are released from livers of normal and phenobarbital-treated rats during perfusion in either the anterograde or the retrograde direction at maximal rates around 13-15 mumol/g/hr. The formation of S-(1-chloro-4-nitrophenyl)-glutathione and S-(2,4-dinitrophenyl)-glutathione by the liver decreased the amount of 366-nm light reflected from the liver surface detected with a large-tipped (2 mm) fiberoptic light guide. Initial rates of decrease in reflected light correlated highly with maximal rates of conjugate formation by the liver. Subsequently, micro-light guides were placed on periportal and pericentral regions of the liver lobule. Rates of glutathione adduct formation were calculated from the proportion of the total change in rate of reflected 366-nm light which occurred in each region and the overall rate of product formation by the liver. Changes in the reflectance signal require reduced glutathione (GSH) and were shown to originate from intracellular conjugate formation and not from adducts in the bile canaliculus. Livers from normal rats produced conjugated products from DCNB (100 microM) at maximal rates of 14 and 15 mumol/g/hr in periportal and pericentral regions of the liver lobule, respectively. With CDNB as substrate, changes in reflected light at 366 nm were detected nearly exclusively in periportal regions of the lobule in livers from normal rats. In sharp contrast, CDNB and DCNB were conjugated exclusively in periportal regions of the lobule at rates of 21-22 mumol/g/hr in livers from phenobarbital-treated rats (i.e., the reflectance signal was not altered by these substrates in pericentral areas). When CDNB and DCNB were infused into livers from phenobarbital-treated rats perfused in the retrograde direction, decreases in reflected light at 366 nm were detected initially in pericentral areas followed in about 12 min by changes in periportal regions. Maximal rates of adduct formation in both regions reached 25 mumol/g/hr during perfusion in the retrograde direction. Thus, pericentral regions indeed possess the capacity to conjugate both CDNB and DCNB. When glutathione synthesis was inhibited with L-buthionine sulfoximine treatment (6 mmol/kg), which partially depletes GSH, CDNB was conjugated in both periportal and pericentral regions of the liver lobule in livers from phenobarbital-treated rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Attenuated response to nomifensine in rats during a swim test following lesion of the habenula complex.

Male Lister rats with bilateral lesions of the habenula nuclei were observed during two consecutive phases of a swim test. During the first phase of the test, when escape was not possible, lesioned animals demonstrated fewer changes of behaviour. Lesioned animals failed to utilise an introduced external cue and escape route in the second part of the test. Control rats treated with the antidepressant nomifensine showed few changes of behaviour during the inescapable phase of the test but an enhanced ability to escape. Nomifensine produced no improvement of escape behaviour in lesioned animals, suggesting that this behavioural effect of nomifensine in controls is dependent on the habenula relay. The data also suggest that more than one response in swim tests can serve as an index of depression.

Analysis of Variance↗
PubMed1985

Interoceptive stimuli produced by an anxiogenic drug are mimicked by benzodiazepine antagonists in rats pretreated with isoniazid.

Treatments which increase gamma-aminobutyric acid (GABA) neurotransmission or those which cause stimulation of benzodiazepine receptors, produce anxiolytic effects; but the converse (anxiogenic) effects have not been reported after suppression of either system alone. We report here that simultaneous inhibition of these two systems produces anxiogenic effects. After partial depletion of GABA by isoniazid, the benzodiazepine antagonists, RO 15-1788 and CGS8216, produced pentobarbital reversible anxiogenic effects in the pentylenetetrazol discrimination assay. These results support the hypothesis that GABA and endogenous anxiolytics mutually facilitate modulation of anxiety. They also indicate that there may exist endogenous anxiogenics which act at non-benzodiazepine recognition sites.

Animals↗
PubMed1985

Intravenous drug abusers and the acquired immunodeficiency syndrome (AIDS). Demographic, drug use, and needle-sharing patterns.

We studied the demographic characteristics, drug use patterns, and sexual habits of intravenous (IV) drug abusers to further define this population at risk for acquired immunodeficiency syndrome (AIDS). Sixteen IV drug abuser patients with AIDS, 24 IV drug abuser patients with AIDS-related complex (ARC), and 14 IV drug abuser controls without evidence of AIDS or ARC were evaluated. The subjects in each group were similar demographically, in drug use practice, and in sexual orientation and experience. Of the AIDS and ARC patients, 34 (88%) of 40, including all seven homosexual men, shared needles, as did all drug abusers without AIDS or ARC. Seventy-four percent of patients, including all homosexual men, attended "shooting galleries," where anonymous multiple-partner needle sharing took place. Needle sharing supports the hypothesis of AIDS transmission by a blood-borne route, can explain the spread of AIDS and the high rate of seropositivity to the putative AIDS agent among IV drug abusers, and is a logical link between IV drug abusers and male homosexuals, the two largest groups with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Findings on a relationship between type A behavior and headaches.

Based on answers to a headache questionnaire college women were classified on a two-dimensional array according to their relative frequencies of both vascular (migraine) and tension (muscle contraction) pain. The various groups were then compared on a measure of the coronary-prone Type A behavior pattern. In two independent surveys, one with 237 respondents and one with 206 respondents, increasing frequencies of both types of headaches were significantly associated with higher scores on the Type A scale from the Jenkins Activity Survey. The findings support prior data from a client population, also reported, and suggest appropriate therapeutic interventions for headache relief. They also clearly show that a behavior pattern which has been associated with coronary artery disease now can be considered to have implications for other problems as well.

Coronary Disease↗
PubMed1984

In vitro activities of amphotericin B in combination with four antifungal agents and rifampin against Aspergillus spp.

Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility with a microtiter plate system in buffered yeast-nitrogen base and in buffered minimal essential medium. Isolates were tested against amphotericin B, flucytosine, rifampin, ketoconazole, ICI 153,066, and Bay n 7133 and against combinations of amphotericin B with each of the other five drugs. Combinations of amphotericin B and rifampin were the most active against all three species of Aspergillus. Flucytosine combined with amphotericin B produced little or no reduction of the MICs at which 90% of the strains were inhibited compared with amphotericin B alone. With one exception, the addition of ketoconazole, ICI 153,066, or Bay n 7133 to amphotericin B did not consistently alter the MICs. The addition of ICI 153,066 markedly increased the MICs of amphotericin B against the A. flavus isolates in both media. When the azoles were tested alone, Bay n 7133 was the most active against A. fumigatus, but was two- to fivefold less active against A. flavus. Ketoconazole was the most active azole against A. flavus.

Amphotericin B↗
PubMed1984

Enhancement of the in vitro activity of amphotericin B against Aspergillus spp. by tetracycline analogs.

Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility to amphotericin B alone and in combination with fixed concentrations of tetracycline, doxycycline, or minocycline, using buffered minimal essential medium in microtiter plates. Enhanced inhibitory activity was seen, especially with combinations of amphotericin B and minocycline. Synergistic activity between amphotericin B and minocycline was observed in each of five isolates of each species when tested in a checkerboard dilution scheme. Time-kill curves demonstrated killing an A. fumigatus isolated at concentrations of amphotericin B that were four- or eightfold lower in the presence of 5 or 15 micrograms of minocycline per ml than with amphotericin B alone. Of the tetracycline analogs tested, minocycline has the greatest activity against A. fumigatus, A. flavus, and A. niger conidia when potentiated by amphotericin B.

Amphotericin B↗
PubMed1983

Immunodeficiency in female sexual partners of men with the acquired immunodeficiency syndrome.

Because the current outbreak of acquired immunodeficiency syndrome (AIDS) among previously healthy adults may be caused by a transmissible biologic agent, and because it may be preceded by immunologic abnormalities with or without a prodromal illness, we studied seven female sexual partners of male patients with the syndrome. The male patients were all drug abusers. One of the seven women was found to have the full-blown syndrome, a second had an illness consistent with the prodrome of AIDS (generalized lymphadenopathy, lymphopenia, and a decreased ratio of helper to suppressor T cells), and four others had generalized lymphadenopathy or lymphopenia, with or without a decreased ratio of helper to suppressor T cells. Only one woman had no abnormalities. These findings suggest that AIDS may be transmitted between heterosexual men and women.

Acquired Immunodeficiency Syndrome↗
PubMed1983

A geographic cluster of testicular seminomas.

There have been many reports of space-time clusters of patients with Hodgkin's disease, childhood leukemia and Burkitt's lymphoma. We present a tight space cluster of 4 men with pathologically confirmed testicular seminomas. None of the men had any known reason to be at increased risk for testicular cancer. They all lived in the same immediate neighborhood for at least 7 years. There were 2 sources of potential carcinogens in the area. It is concluded that testicular cancer may have developed in these men as a result of exposure to environmental carcinogens.

Adult↗