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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 163 records · Page 9Linked to original sources
PubMed1997

Subtypes of HIV-1 and the impact of dual infections of HIV-1 and measles virus on micronutrient levels of pregnant women in Harare, Zimbabwe.

OBJECTIVE: To determine subtypes of HIV-1, simultaneous prevalence of HIV-1 and measles virus antibodies and their impact on micronutrient levels of pregnant women in Harare, Zimbabwe. DESIGN: Cross sectional. SETTING: Budiriro and Edith Opperman Antenatal Clinics Harare; Departments of Medical Microbiology, Medical Laboratory Technology and Institute of Food, Nutrition and Family Sciences, University of Zimbabwe. SUBJECTS: Pregnant women attending antenatal clinics in Harare, Zimbabwe. MAIN OUTCOME MEASURES: HIV-1 subtypes, measles virus seropositivities and levels of micronutrients among the pregnant women. RESULTS: Results showed that 101 (22.7%) out of a total of 444 pregnant women screened were HIV-1 positive. A separate group of 238 (inclusive of the 444) were screened for measles antibody and 118 (49.5%) were positive, whereas 41 (17.2%) were HIV-1 positive. Thirty five (29.7%) were seropositive for both HIV-1 and measles virus (simultaneous infection). HIV-1 subtypes revealed subtype C (70.4%) as the predominant subtype. HIV-1 subtypes B, A and D accounted for 40.8%, 39.8% and 22.4% respectively whereas HIV-1 subtypes E and F were not detected. Dual infections showed that 37.7%, 36.7%, 7.1% and 4.4% harboured subtypes A and C; B and C; A and D and B and D respectively. Multiple infections with subtypes A, B, C and D (5.1%) were also recorded whereas 9.2% were non-reactive. Results on micronutrients portrayed that HIV-1 positive pregnant women had significantly lower zinc than the control but co-infection with measles virus did not cause further decrease. Infection by either HIV-1 or measles virus increased serum copper (p < 0.05) but co-infection by the two viruses reduced the copper level significantly (p < 0.05). HIV-1 seropositivity did not affect serum magnesium level but was lower (p < 0.05) in women positive for both HIV-1 and measles virus. CONCLUSION: This is a single report on HIV-1 infection, HIV-1 subtypes, simultaneous prevalence of HIV-1 and measles virus antibodies and their impact on micronutrient levels of pregnant women in Harare, Zimbabwe. The study is of nutritional, clinico-epidemiologic importance.

Amino Acid Sequence↗
PubMed1997

HIV infection and HIV-1 clades among pregnant women in Harare, Zimbabwe.

OBJECTIVE: To determine HIV-1 seropositivity and HIV-1 clades/subtypes among pregnant women attending different clinics in Harare, Zimbabwe. DESIGN: A prospective study. SUBJECTS: 206 pregnant women attending Edith Opperman and Budiriro clinics in Harare. MAIN OUTCOME MEASURES: Frequency distribution of the various HIV-1 clades and rate of HIV-1 seropositivity. RESULTS: Results obtained showed that out of the 206 pregnant women screened, 60 (29.1%) were HIV-1 seropositive. The most predominant clade was HIV-1 clade C (66.6%) whereas HIV-1 clades A and B accounted for 48.3% and 33.3% of HIV-1 clades respectively. Results also revealed dual infections with clades A and C (45%), A and D (10%), B and C (30%) and multiple infections with A, B, C and D (6.6%) whereas two (3.3%) were non-reactive. CONCLUSION: Finally, the data on HIV-1 clades are of immense immunological, molecular and epidemiological importance in Harare, Zimbabwe and should serve as base line data for future investigations in the country.

Amino Acid Sequence↗
PubMed1996

Conserved secondary structure in the actinorhodin polyketide synthase acyl carrier protein from Streptomyces coelicolor A3(2) and the fatty acid synthase acyl carrier protein from Escherichia coli.

The acyl carrier protein (ACP) of Streptomyces coelicolor A3(2) functions as a molecular chaperone during the biosynthesis of the polyketide actinorhodin (act). Here we compare structural features of the polyketide synthase (PKS) ACP, determined by two-dimensional 1H-NMR, with the Escherichia coli fatty acid synthase (FAS) ACP. The PKS ACP contains four helices (residues 7-16 [A], 42-53 [B], 62-67 [C], 72-86 [D]), and a large loop (residues 17-41) having no defined secondary structure with the exception of a turn between residues 21 and 24. The act ACP shows 47% sequence similarity with the E. coli FAS ACP and the results demonstrate that the sequence homology is extended to the secondary structure of the proteins.

Acyl Carrier Protein↗
PubMed1996

Effects of metyrapone on expression of CYPs 2C11, 3A2, and other 3A genes in rat hepatocytes cultured on matrigel.

Hepatocytes cultured on matrigel express many liver-specific functions, but the levels and activities of the predominant male-specific rat hepatic CYPs, 3A2 and 2C11, decline rapidly in culture. Metyrapone maintains the level of total cytochrome P450 of rat hepatocytes in primary culture, but the mechanism underlying this effect has not been completely elucidated. The present study sought to determine whether metyrapone acts solely to stabilise CYP proteins in rat hepatocytes cultured on matrigel, or whether it also influences mRNA levels of the encoding genes. Metyrapone maintained the level of total cytochrome P450 in cultured hepatocytes so that values were > 200% of those found in untreated control cells 24 hr after isolation. At this time, CYP3A2-mediated testosterone 6 beta-hydroxylation was approximately 7-fold higher in hepatocytes cultured in the presence of metyrapone than in control cells, and CYP2C11-dependent testosterone 2 alpha- and 16 alpha-hydroxylation activities were between 2 and 3-fold greater. The results inferred from catalytic activities were supported by immunoquantitation of CYP3A and 2C11 proteins. The trend of increased CYP protein levels in metyrapone-treated cells continued throughout the 48-hr culture period. In control cells, CYP3A2 and 2C11 mRNA levels fell abruptly in culture to reach values at 24 hr that were < 30% of those in freshly isolated cells; addition of metyrapone failed to arrest this fall. However, treatment of cells with metyrapone considerably elevated levels of one or more CYP3A subfamily mRNA species, as detected by a riboprobe based on the cDNA for CYP3A1 ("CYP3A1-like mRNA') that were demonstrated, by another riboprobe, not to be CYP3A2 or RNCYP3AM. RT-PCR of mRNA prepared from cultured hepatocytes, followed by restriction mapping of the cloned cDNAs was used to characterise the CYP3A induced by metyrapone. This revealed that elevated levels of the CYP3A1-like mRNA were attributable to induction of RL33/cDEX mRNA; there were no CYP3A1 cDNAs isolated from these cells. These data are interpreted as indicating that metyrapone stabilises the expression of cytochrome P450 in culture by both pre- and posttranslational mechanisms. The particular mechanism employed is gene-specific, whereby even the highly homologous genes CYP3A2, RL33/cDEX and, possibly, RNCYP3AM are subject to different types of regulation in the presence of metyrapone.

Animals↗
PubMed1996

Expression of a phosphorylated isoform of MAP1B is maintained in adult central nervous system areas that retain capacity for structural plasticity.

Microtubule-associated protein IB (MAP1B) is the first MAP to be detected in the developing nervous system, and it becomes markedly down-regulated postnatally. Its expression, particularly that of its phosphorylated isoform, is associated with axonal growth. To determine whether adult central nervous system (CNS) areas that retain immunoreactivity for MAP1B are associated with morphological plasticity, we compared the distribution of a phosphorylated MAP1B isoform (MAP1B-P) to the distribution of total MAP1B protein and MAP1B-mRNA. Although they were present only at very low levels, both protein and message were found ubiquitously in almost all adult CNS neurons. The intensity of staining, however, varied markedly among different regions, with only a few nuclei retaining relatively high levels. MAP1B-P was restricted to axons, whereas total MAP1B was present in cell bodies and processes. Relatively to total MAP1B protein and its mRNA, MAP1B-P levels decreased more dramatically with maturation, and they were detectable in only a few specific areas that underwent structural modifications. These included primary afferents and motor neurons, olfactory tubercles, habenular and raphe projections to interpeduncular nuclei, septum, and the hypothalamus. The distribution pattern of MAP1B-P was compared to that of the embryonic N-CAM rich in polysialic acid (PSA-NCAM). We found that the PSA-NCAM immunostaining was largely overlapped with that of MAP1B-P in the adult CNS. These results suggest that, like PSA-NCAM, MAP1B may be one of the molecules expressed during brain development that also plays a role in structural remodeling in the adult.

Animals↗
PubMed1996

Characterization of the in vivo inhibition of rat hepatic microsomal aldehyde dehydrogenase activity by metyrapone.

Microsomal aldehyde dehydrogenase (mALDH; EC 1.2.1.3) has been proposed to catalyze the oxidation of various aldehydic products of lipid peroxidation, but the regulation of the enzyme has not been characterized. Metyrapone administration (100 mg/kg, i.p.) produced a rapid decline in the rates of mALDH-catalyzed decanal dehydrogenation; other xenobiotics were generally without effect. Thus, a 22% decrease in activity was detected 2 hr following metyrapone administration, and 52% of the activity remained at 6 hr. The decrease in microsomal decanal dehydrogenation was also dose-dependent with 70, 43, and 12% of the control activity remaining following pretreatment with 25, 100, and 250 mg/kg metyrapone, respectively. This disease in microsomal decanal dehydrogenase activity occurred without a change in mALDH immunoreactive protein, and metyrapone did not inhibit the activity in vitro. The kinetic analysis revealed similar decreases in the maximal reaction velocities (Vmax) for both decanal and NAD in the metyrapone-treated group (200 +/- 10 and 190 +/- 20 nmol NADH produced/min/mg protein, respectively) compared with the untreated group (330 +/- 10 and 350 +/- 20 nmol NADH produced/min/mg protein, respectively), but the Michaelis constants (Km) were unchanged. These data are consistent with the in vivo inactivation of a portion of the mALDH enzyme. A possible consequence of the in vivo inhibition of this enzyme by metyrapone could be the accumulation of toxic aldehydes in the vicinity of the microsomal membrane following lipid peroxidation.

Aldehyde Dehydrogenase↗
PubMed1996

Inhibition of microsomal cytochromes P450 in rat liver by the tricyclic antidepressant drug desipramine and its primary oxidized metabolites.

N-Monoalkyl substituted tricyclic antidepressants like desipramine (DES) undergo cytochrome P450 (P450)-mediated biotransformation in liver to produce inhibitory metabolite-intermediate (MI) complexes with the enzyme. However, additional oxidation pathways that generate isolable metabolites have also been identified, so that the relationship between MI complexation and total oxidative metabolism is unclear. The present study investigated the capacity of DES and three putative metabolites (2-hydroxy- and 10-hydroxy-DES and N,N-didesmethylimipramine; DIDES) to elicit MI complexation and inhibit P450-dependent activities in rat liver. MI complexation of P450 was produced by DES, but not with the three metabolites, in NADPH-supplemented microsomes. Consistent with this finding, inhibition of testosterone hydroxylation pathways was enhanced markedly by prior incubation of DES with NADPH and microsomes. Direct addition of DIDES to incubations resulted in significant inhibition of P450 activities (IC50s of 35 and 29 microM against estradiol 6 beta- and 16 alpha-hydroxylation mediated by P450s 3A2 and 2C11, respectively). Neither 2-hydroxy- nor 10-hydroxy-DES directly inhibited testosterone hydroxylation (IC50s > 100 microM). However, after a preincubation step between these metabolites and NADPH-fortified microsomes, enhanced inhibition of reactions mediated by P450 3A2 and P450 2C11/2A1 was produced by 2-hydroxy-DES and 10-hydroxy-DES, respectively. Metabolism of DES to DIDES and 2-hydroxy-DES was estimated as 7.77 +/- 0.48 nmol/mg protein/hr (10-hydroxy-DES was not detected). It is likely that secondary oxidized metabolites derived from 2-hydroxy-DES, as well as the primary metabolite DIDES, may contribute to the inhibition of P450 activity during DES biotransformation. These results indicate that the 2-hydroxy-, 10-hydroxy-, and N-desmethyl-metabolites of DES are not involved in MI complexation, but complexation is not the sole mechanism by which DES inhibits microsomal drug oxidation that may lead to pharmacokinetic drug interactions.

Animals↗
PubMed1996

The importance of 2,3-dimercaptopropinol (British anti-lewisite, BAL) in the trypanocidal activity of topical melarsoprol.

Both melarsomine dichlorhydrate (mel Cy, Cymelarsan) and melarsen oxide can be dissolved in dimethylsulfoxide and converted into a gel by the addition of hydroxypropylcellulose. When Trypanosoma brucei brucei-infected mice are treated topically with these gels the circulating trypanosomes are rapidly cleared from the circulation but the infections relapse soon after the last application. However, when these two compounds are allowed to react with 2,3-dimercaptopropinol (British anti-lewisite, BAL) and form "melarsoprol" their efficacy, especially in the case of mel Cy, is restored to that of commercial melarsoprol (Arsobal) and trypanosomes in the central nervous system (CNS) can be eliminated. This would indicate that the dimercaptopropinol portion of the molecule does not act solely as an "antidote" to arsenic toxicity, but also plays an important role in the absorption of melarsoprol through the skin and/or blood-brain barrier into the CNS and/or into the trypanosome.

Administration, Topical↗
PubMed1996

Influence of soyabean meal supplementation on the resistance of Scottish blackface lambs to haemonchosis.

Protein supplementation improves the resistance of sheep to haemonchosis. This experiment investigated the Scottish blackface breed to establish whether dietary protein supplementation is still beneficial in a genetically resistant breed. Lambs were given either a basal diet or a diet supplemented with soyabean meal to give an additional 80 g crude protein kg dry matter-1. The lambs were given an initial loading dose of Haemonchus contortus, followed by a trickle infection for 10 weeks. The weight gains of the lambs given the supplemented diet were greater and their carcases were leaner, irrespective of infection status. Infected animals on the basal diet were more anaemic and hypoalbuminaemic than animals receiving the supplemented diet, although there were no statistically significant differences in mean worm burdens or faecal egg counts.

Analysis of Variance↗
PubMed1996

Lesion of the habenular efferent pathway produces anxiety and locomotor hyperactivity in rats: a comparison of the effects of neonatal and adult lesions.

Recent studies have implicated the habenula in modulating states of arousal and chronic responses to stress. We examined whether lesion of the habenula efferent pathway, the fasciculus retroflexus (FR), at either 3 (P3) or 70 (P70) days of age affects stress-related anxiety (elevated plus-maze test) and activity levels (open-field test) in rats tested as adults. Both P3- and P70-lesioned rats showed chronically elevated plasma levels of corticosterone. Rats receiving FR lesions as neonates (P3) exhibited greater open arm avoidance on the elevated plus-maze than controls 2 months postoperatively, suggesting a heightened state of anxiety. In contrast, P70-lesioned rats behaved similarly to controls on the plus-maze, but showed increased locomotion and increased grooming in the open field, effects not observed in P3-lesioned rats. When an additional stressful condition was imposed (5 days of social isolation plus 24 h food deprivation) before testing, both FR-lesion groups showed an attenuation of the normal behavioral responses (decreased open-arm entries/time in open arms, increased freezing). The effects of FR lesions on activity and behavioral indices of anxiety may be due to disruption of lateral habenular projections to dopaminergic neurons in the ventral tegmentum and/or projections to regions containing high concentrations of benzodiazepine receptors, the median and dorsal raphe and dorsal periaqueductal gray. Behavioral differences observed as a function of lesion age suggest differential capabilities of P3- and P70-lesioned rats to utilize compensatory mechanisms to correct FR lesion-induced deficits.

Aging↗
PubMed1996

Case management: a new practice model for ET nurses.

An examination of wound, ostomy, and continence nursing practice provides ideas for improving patient care and for role development of the ET nurse. During this period of rapid health care reform, opportunities to expand ET nursing practice must be explored. For many ET nurses, care of the patient with an ostomy remains a primary focus. The fitting of prosthetic equipment and patient education concerning ostomy care may not, however, be enough to demonstrate the impact of ET nursing care on the outcome of patients with an ostomy. Caring for the patient undergoing gastrointestinal surgery by means of a case management model is a new option for ET nurses. Nurse case managers focus on the patient and the impact of illness from admission until discharge. They are accountable for coordinating the multidisciplinary team who cares for the patient and for the evaluation of outcomes. ET nurses must evaluate the outcomes of their care to demonstrate the continued need for our specialty practice. This article describes the efforts of ET nurses at a tertiary care center in the Midwest to develop a case management system for patients undergoing gastrointestinal surgery within their practice. The process of developing a critical pathway, or care map, is also described.

Case Management↗
PubMed1996

All-trans-retinoic acid 4-hydroxylation in human liver microsomes: in vitro modulation by therapeutic retinoids.

All-trans retinoic acid (ATRA) induces remission in patients with acute promyelocytic leukaemia. Other retinoids, including 9-cis- and 13-cis-retinoic acid (9-cis- and 13-cis-RA), are now being evaluated for their therapeutic potential. The elimination of ATRA is partially dependent on cytochrome P450 (P450)-mediated 4-hydroxylation, but the interaction of other retinoids with P450 has not yet been assessed. In the present study 9-cis- and 13-cis-RAs, as well as all-trans-retinol and three isomeric retinals were found to inhibit ATRA 4-hydroxylation in human hepatic microsomes, but the arotinoids acitretin and etretinate were not inhibitors 9-cis- and 13-cis-RA were competitive inhibitors of ATRA 4-hydroxylation (Ki:Km ratios 3.5 +/- 0.8 and 6.3 +/- 0.5, respectively) suggesting that these retinoids are alternate, but inferior, substrates for the P450 enzyme(s) that mediate the activity. The biotransformation of therapeutic retinoids containing the beta-ionone ring system is likely to involve the microsomal ATRA 4-hydroxylase P450.

Antineoplastic Agents↗
PubMed1996

Topical chemotherapy for experimental African trypanosomiasis with cerebral involvement: the use of melarsoprol combined with the 5-nitroimidazole, megazol.

Megazol, one of a number of related 5-nitroimidazoles, can be dissolved in dimethylsulphoxide and the solution can be converted into a gel by the addition of hydroxypropylcellulose which facilitates the ease and accuracy of administration. This megazol gel, when used in combination with melarsoprol (3.6%) in propylene glycol gel, will cure experimental CNS-trypanosomiasis in mice. A single application of 0.1 ml of melarsoprol (3.6%) gel plus 0.1 ml of either 8 or 16 mg/ml megazol gel successfully treated experimental CNS-trypanosomiasis while two consecutive days' treatment with 0.05 ml melarsoprol and 0.1 ml of 16 or 32 mg/ml megazol gels also produced satisfactory cures.

Administration, Topical↗
PubMed1996

Effects of traumatic brain injury on the cholinergic system in the rat.

Rats subjected to a mild to moderate fluid percussion injury exhibit memory deficits that are similar to rats that have received lesions of the septohippocampal system. Because the cholinergic system plays a major role in septohippocampal function, we studied the kinetics of the synthetic enzyme for acetylcholine, choline acetyltransferase (ChAT), at 1 h, 24 h, or 5 days after a fluid percussion injury. Decreases in ChAT activity were found in the dorsal hippocampus (25%), frontal (32%), and temporal (23%) cortices 1 h after injury. In the parietal cortex, a greater than 50% increase in ChAT activity was observed at all time intervals assessed. At 5 days after TBI, there was an 18% increase in ChAT activity in the medial septal area. These data provide evidence that a mild to moderate fluid percussion injury produces changes in the cholinergic system in brain areas related to memory.

Analysis of Variance↗
PubMed1996

Restoration of cytochrome P450 2C11 in vitamin A-deficient rat liver by exogenous androgen.

Down-regulation of microsomal androgen-dependent CYP2C11 is produced in male rat liver by dietary vitamin A deficiency. Decreased circulating androgen concentrations also occur in vitamin A-deficient male rats. Both effects are prevented by addition of all-trans-retinoic acid to the diet. The present study evaluated directly whether androgen deficiency may be responsible for the down-regulation of 2C11 in vitamin A-deficient male rats. The major finding was that subcutaneous administration of the androgen methyltrienolone (MT) during the final week of the study restored CYP2C11 protein and its associated steroid 16alpha-hydroxylation activities to control levels; CYP2C11 mRNA was also restored. Despite the efficient restoration of CYP2C11 at a pretranslational level, no alteration in vitamin A status was apparent and animals remained vitamin A deficient after MT treatment. The possibility was assessed that vitamin A can maintain the microsomal content of CYP2C11 in normal liver. However, in contrast to MT, administration of ATRA to gonadectomized male rats did not restore 2C11 in liver. These findings establish that the major effect of vitamin A deficiency on CYP2C11 in male rat liver is mediated indirectly by androgen deficiency.

Androstenedione↗
PubMed1996

Prevention and treatment of alcohol-related problems: an international medical education model.

Alcohol abuse and alcoholism are among the world's most pressing public health concerns. Research has shown that while primary care physicians are in a good position to screen for alcohol-use disorders and to aid in treating these problems, they tend to identify only a small percentage of patients with such disorders and they rarely intervene with these persons. This situation is probably attributable to the fact that medical students worldwide are taught very little about alcohol-related problems. Clearly there is an urgent need to educate the world's doctors about preventing, diagnosing, and treating alcohol abuse and addiction. In this paper, the authors describe a model international program for educating physicians about alcohol-related problems that was developed by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in cooperation with the Center for Addiction Research and Education (CARE) at the University of Wisconsin-Madison. They describe the components of the initiative's "trainer-development" approach and critical issues in implementing the program in other countries. Finally, they discuss how the program was successfully implemented in Poland and describe the NIAAA's plans for introducing the model in several other countries.

Alcoholism↗
PubMed1996

Using patient feedback for quality improvement.

This article describes the results of a study designed to understand h how health care organizations use patient feedback. The article examines the organizational factors and the barriers that influence patient feedback use and concludes with propositions that can serve to guide future action and research in this area.

Data Collection↗