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Biomedical subjects

R George

Publications and source records attributed to R George.

At least 127 records · Page 7Linked to original sources

Community HIV/AIDS teams.

This paper describes a consecutive series of 103 patients with HIV and AIDS related illnesses who were referred to, and remained in, the care of two community teams. The characteristics of the patients are outlined and the early experiences of the teams are described. The findings of this study should assist doctors and nurses caring for patients with HIV and AIDS related illnesses in the community, and provide valuable data for service planners.

Acquired Immunodeficiency Syndrome↗

Risk factors for HIV-2 infection in Guinea-Bissau.

To define the epidemiology of HIV-2 infection, we conducted a case-control study among hospitalized patients at an acute care hospital in Bissau, Guinea-Bissau, a country with endemic HIV-2 infection. Among 128 patients with various diagnoses, 23 (18%) were positive for HIV-2 by ELISA and Western blot. One of these patients was serologically reactive for HIV-1 also, but PCR and viral culture revealed the presence of HIV-2 only. To study risk factors, behaviors, and AIDS knowledge related to the acquisition of HIV infection, 22 HIV-2-seropositive and 21 seronegative hospitalized patients were given a physical examination and administered a questionnaire. Among women, transfusion was associated with HIV-2 infection (OR = 14.4, p = 0.02); among men, sex with a prostitute was the principal risk factor (OR = undefined, p = 0.02). Although 79% of HIV-infected patients and controls had heard of AIDS, only 17% of all study participants and 50% of males reporting sex with prostitutes had used condoms in the previous year. These data suggest that the risk factors for HIV-2 infection are similar to those for HIV-1 and support previous studies showing that HIV-2 is the predominant HIV in Guinea-Bissau. Efforts to decrease transmission of HIV-2 should include screening for HIV-2 in blood for transfusion in endemic areas (now done in Bissau) and education about the risk of sexual transmission.

Adolescent↗

The relationship of microbial pathogens to acute infectious diarrhoea of childhood.

Bacterial, viral and parasitic enteric pathogens were detected in 692 of 916 children below 36 months of age with acute diarrhoea and in 289 of 587 matched controls. The rates of identification of only four groups of pathogens, rotavirus, Shigellae, Salmonella typhimurium and enterotoxigenic E. coli, were significantly higher in the patients. The prevalence of a variety of other enteric pathogens was similar in controls of patients. Shigellosis had a characteristic clinical profile but none of the other agents could be suspected on clinical grounds. The high prevalence of pathogens in controls suggested that the population may be partially protected against a variety of enteric pathogens and that final common pathways leading to diarrhoea may be activated by changes in the microbial ecology of the gut lumen.

Acute Disease↗

An investigation of nosocomial infection with Corynebacterium jeikeium in surgical patients using a ribosomal RNA gene probe.

Twelve strains of multi-resistant Corynebacterium jeikeium isolated during a one year period in a surgical unit in Innsbruck were analyzed with regard to their plasmid content, antibiotic susceptibility, and the use of ribosomal ribonucleic acid (rRNA) to probe restriction fragment length polymorphism (RFLP). Plasmids were detected in five of the strains. Southern blotting of genomic DNA digested with HindIII or PvuII and hybridized with a biotin-labelled cDNA probe derived from total rRNA revealed characteristic banding patterns. Seven of the 12 strains showed similar RFLP profiles, consistent with them being related epidemiologically. The minor changes in RFLP profiles observed in these seven strains suggest that Corynebacterium jeikeium may be subject to genetic drift over a relatively short time span. Strains from other sources, included for comparison, differed markedly from those from Innsbruck. Patterns of antibiotic susceptibility which appeared not to be plasmid encoded, correlated broadly with RFLP profiles. This study suggests that strains of Corynebacterium jeikeium may be transferred between hospital patients.

Corynebacterium↗

Reye and Reye-like syndromes: results of a pilot study in Peninsular Malaya, 1986.

A pilot epidemiologic study of all cases of Reye and Reye-like syndromes was undertaken at 8 representative major hospitals in Peninsular Malaya from January 1st to December 31st 1986. The cases were classified as definitive Reye's syndrome, clinical Reye's syndrome and encephalo-hepatopathies. Less than 50% of cases reviewed fulfilled the National Center for Disease Control criteria for clinical Reye's syndrome. Causes of Reye-like syndromes/encephalo-hepatopathies included fulminant hepatitis, Japanese B encephalitis, dengue, septicaemia, and complex febrile fits. It was not possible to differentiate clinical Reye's syndrome from the other encephalo-hepatopathies by either the clinical features (except for jaundice) or biochemical parameters. Liver biopsy is necessary for a definitive diagnosis of Reye's syndrome in Malaysia, because of the high prevalence of Reye-like diseases. The mortality rate in the 2 groups of patients is similar. Ingestion of salicylates was not found to be significantly associated with Reye and Reye-like syndromes in this study.

Diagnosis, Differential↗

Studies on the purified Na+,Mg(2+)-ATPase from Acholeplasma laidlawii B membranes: a differential scanning calorimetric study of the protein-phospholipid interactions.

The purified Na+,Mg2(+)-ATPase from the Acholeplasma laidlawii B plasma membrane was reconstituted with dimyristoyl phosphatidylcholine and the lipid thermotropic phase behavior of the proteoliposomes formed was investigated by differential scanning calorimetry. The effect of this ATPase on the host lipid phase transition is markedly dependent on the amount of protein incorporated. At low protein/lipid ratios, the presence of increasing quantities of ATPase in the proteoliposomes increases the temperature and enthalpy while decreasing the cooperativity of the dimyristoyl phosphatidylcholine gel to liquid-crystalline phase transition. At higher protein/lipid ratios, the incorporation of increasing amounts of this enzyme does not further alter the temperature and cooperativity of the phospholipid chain-melting transition, but progressively and markedly decreases the transition enthalpy. Plots of lipid phase transition enthalpy versus protein concentration suggest that at the higher protein/lipid ratios each ATPase molecule removes approximately 1000 dimyristoyl phosphatidylcholine molecules from participation in the cooperative gel to liquid-crystalline phase transition of the bulk lipid phase. These results indicate that this integral transmembrane protein interacts in a complex, concentration-dependent manner with its host phospholipid and that such interactions involve both hydrophobic interactions with the lipid bilayer core and electrostatic interactions with the lipid polar head groups at the bilayer surface.

Acholeplasma laidlawii↗

Cholesterol-mediated regulation of HMG-CoA reductase in microsomes from human skin fibroblasts and rat liver.

3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was determined in microsomes from human skin fibroblasts and rat liver that had been variously manipulated in vivo or in tissue culture to up- and down-regulate the enzyme. The cholesterol content of these microsomal preparations was then altered by depletion to or enrichment from either cholesterol-free or cholesterol-rich lipid vesicles. Microsomes from human skin fibroblasts responded to cholesterol depletion by increasing HMG-CoA reductase activity and by decreasing it in response to cholesterol enrichment. This was independent of the initial enzyme activity or the tissue culture conditions. Alterations in cholesterol content of rat liver microsomes in vitro failed to demonstrate any significant changes in HMG-CoA reductase activity whether the microsomes started with low enzyme activity (cholesterol-fed rats) or with high enzyme activity (cholestyramine-treated rats). The results are discussed in relation to previously published data and in respect to differences in the control of the human skin fibroblast and rat liver enzymes.

Animals↗

Effects of acute and chronic administration of (+)-SKF 10,047 on body temperature in the rat: cross-sensitization with phencyclidine.

The current study investigated the effects of acute and chronic administration of (+)-SKF 10,047 on body temperature in rats. The effect of phencyclidine on body temperature in chronically (+)-SKF 10,047-treated rats was also investigated. The acute administration of (+)-SKF 10,047 at doses of 5 to 40 mg/kg s.c. did not alter body temperature; however, 80 mg/kg produced hypothermia. In contrast, chronic administration of (+)-SKF 10,047 (5-20 mg/kg) produced dose-dependent hyperthermia when tested on day 7 and 10 of chronic treatment. Moreover, sensitization to the hyperthermic effects occurred as the degree of hyperthermia was greater on day 10 compared to day 7. Phencyclidine (20 mg/kg s.c.) produced hypothermia in rats chronically treated with saline for 13 days, but hyperthermia in rats chronically treated with 20 mg/kg of (+)-SKF 10,047 for the same duration. The hyperthermic effect of chronic (+)-SKF 10,047 treatment is similar to the previously reported dose-dependent hyperthermia in chronically phencyclidine-treated animals. The cross-sensitization of chronically (+)-SKF 10,047-treated rats to the hyperthermic effects of phencyclidine supports the hypothesis that there may be common mechanisms underlying the chronic effects of these drugs on body temperature.

Animals↗

Determination of the loci of action of phencyclidine on the CNS-pituitary-adrenal axis.

Phencyclidine (PCP) markedly stimulates the pituitary-adrenal axis in the rat, inducing the release of adrenocorticotropin (ACTH) and corticosterone. However, the site or sites where PCP produces these effects is not known. This study sequentially examined the effects of PCP on the different components of the central nervous system-pituitary-adrenal axis. PCP did not produce corticosterone release in dispersed adrenal cells in vitro, nor did it stimulate the release of corticosterone in hypophysectomized rats, showing that PCP-induced corticosterone release in intact animals is secondary to the release of ACTH from the pituitary. PCP failed to alter either the basal or the corticotropin releasing factor-induced release of ACTH from superfused pituitaries in vitro, indicating that PCP does not act directly at the level of the pituitary. PCP increased plasma levels of ACTH in adrenalectomized rats, demonstrating that PCP does not stimulate the release of ACTH only by blocking glucocorticoid negative feedback mechanisms. PCP stimulated the release of both ACTH and corticosterone when given by injection directly into brain via the lateral cerebral ventricles. These results indicate that PCP activates the pituitary-adrenal axis by acting at a site or sites within the central nervous system, leading to the subsequent release of ACTH from the pituitary.

Adrenocorticotropic Hormone↗

Naloxone does not produce withdrawal hypothermia in chronically phencyclidine-treated rats.

Naloxone-induced hypothermia is a sensitive indicator of mu-type opiate dependence in the rat. The present study investigated whether naloxone produces hypothermia in chronically PCP-treated rats. Rats were given daily injections of saline or PCP (10.0 mg/kg s.c.) for 7 days, and on day 8 challenged with naloxone (2.0 mg/kg s.c.). There were no differences between chronic saline- and PCP-treated subjects, indicating that the repeated administration of 10.0 mg/kg per day of PCP does not produce mu-type opiate dependence as reflected by naloxone-precipitated hypothermia.

Animals↗

Studies on the purified, lipid-reconstituted (Na+ + Mg2+)-ATPase from Acholeplasma laidlawii B membranes. Dependence of enzyme activity on lipid headgroup and hydrocarbon chain structure.

The purified (Na+ + Mg2+)-ATPase from Acholeplasma laidlawii B membranes was successfully reconstituted with a number of different phospho- and glycolipids, and the ability of these lipids to support the function of this enzyme was evaluated by their ability to increase the specific activity of the purified enzyme and by their ability to restore its lipid-phase state-dependent properties which were lost during purification. The incorporation of this ATPase into liposomes composed of the endogenous membrane lipids of the organism, or of zwitterionic phospholipids such as phosphatidylcholine or phosphatidylethanolamine, results in a full reconstitution of its activity and its lipid-phase state-dependent properties. In contrast, anionic phospholipids alone, or in combination with zwitterionic phospholipids at concentrations higher than 10 mol % of the anionic phospholipid, cause an irreversible inhibition of this ATPase. However, when combined with neutral glycolipids, larger amounts of anionic phospholipid can be tolerated without enzyme inhibition. Phosphatidylcholines with acyl chains of 14-24 linear carbon atoms and varying degrees of branching and unsaturation successfully reconstitute the enzyme, in marked contrast to the shorter chain homologues, which were ineffective. Our results indicate that the full expression of the activity of the A. laidlawii B ATPase requires a host lipid bilayer membrane of low to moderate negative surface charge which is predominantly liquid-crystalline and of a minimal bilayer thickness. Once such requirements are met, the enzyme exhibits considerable flexibility regarding the nature of the lipids which can effectively support its function. In particular, the activity of the A. laidlawii B ATPase is not very sensitive to lipid "fluidity" in the liquid-crystalline state.

Acholeplasma laidlawii↗

Mevalonate-metabolizing enzymes in Arachis hypogaea.

The activities of the mevalonate metabolizing enzymes-HMG-CoA reductase, mevalonate kinase, mevalonate phosphokinase and mevalonate pyrophosphate decarboxylase -were assayed with the respective substrates in green seedlings of Arachis hypogaea. MVAPP decarboxylase is the rate-limiting step among these enzymes and is inhibited by phenolic acids. Its activity in the seedlings was found to decrease in the absence of light and on treatment with abscisic acid. These results suggest that regulation of isoprene pathway in groundnut seedlings may occur at the level of mevalonate decarboxylation.

Abscisic Acid↗

Characterization of the effects of the acute and repeated administration of MK-801 on the release of adrenocorticotropin, corticosterone and prolactin in the rat.

In addition to its producing profound changes in behavior, phencyclidine (PCP) disrupts neuroendocrine function in the rat. Because PCP binds to PCP as well as sigma receptors, it is not known which receptor type mediates the various effects of the drug. The purpose of the present study was to characterize the effects of the acute administration of enantiomers of MK-801, a compound with a high degree of selectivity for PCP over sigma receptors, on the release of ACTH, corticosterone and prolactin in the rat. In addition, MK-801 was administered daily for eight days in order to test whether tolerance develops to MK-801-induced ACTH and corticosterone release after repeated administration. While both enantiomers of MK-801 markedly increased plasma levels of ACTH and corticosterone, the (+) enantiomer was more potent. Tolerance developed to MK-801-induced increases in ACTH and corticosterone after repeated administration. Plasma prolactin levels were not affected by either the acute or the repeated administration of MK-801. These results suggest that the decrease in plasma levels of prolactin produced by PCP-like drugs is not mediated by PCP receptors, and may be a marker for a sigma receptor-mediated effect.

Adrenocorticotropic Hormone↗

Naloxone does not antagonize PCP-induced stimulation of the pituitary-adrenal axis in the rat.

Phencyclidine (PCP) has been shown to stimulate the pituitary-adrenal axis in the rat. The purpose of the present study was to determine whether opiate receptors are involved in this effect by testing whether pretreatment with the opiate antagonist naloxone can antagonize PCP-induced ACTH and corticosterone release. PCP (10.0 mg/kg) produced increases in plasma ACTH and corticosterone 60 min after s.c. administration. Pretreatment with naloxone (2.0 mg/kg s.c.) did not reduce the rise in plasma levels of ACTH or corticosterone produced by PCP. These results indicate that naloxone-sensitive opiate receptors are not involved in the PCP-induced stimulation of the pituitary-adrenal axis in rats.

Adrenocorticotropic Hormone↗

Metaphit antagonizes phencyclidine-induced hypothermia in the rat.

The acute administration of phencyclidine (PCP) causes hypothermia in the rat. Metaphit (1-[1-(3-isothiocyanatophenyl)cyclohexyl]-piperidine) is a derivative of PCP that has been shown to irreversibly acylate PCP receptors in vitro and in vivo and can antagonize the behavioral and electrophysiological effects of PCP in the rat. The purpose of the present study was to determine whether pretreatment with metaphit can block the hypothermic effects of PCP in the rat. Metaphit or PCP (1.0 mumol/rat) were injected into the lateral ventricles of rats, and 24 hr later the subjects were challenged with PCP (20.0 mg/kg s.c.). Pretreatment with metaphit blocked PCP-induced hypothermia; however, pretreatment with PCP did not affect the subsequent hypothermic response to PCP. These results indicate that the antagonism of PCP-induced hypothermia by metaphit was a specific effect and not due to PCP receptor desensitization.

Animals↗

Comparison of the effects of the acute administration of dexoxadrol, levoxadrol, MK-801 and phencyclidine on body temperature in the rat.

Some of the dioxolanes produce pharmacological effects that have much in common with phencyclidine and phencyclidine-like drugs. Dioxadrol can be resolved into two enantiomers, dexoxadrol and levoxadrol. Dexoxadrol has an affinity for phencyclidine receptors that is much greater than that of levoxadrol, but dexoxadrol and levoxadrol have nearly equal affinities for sigma receptors. The systematic analysis of the relative potencies of dexoxadrol and levoxadrol can be used as an approach to define effects mediated by phencyclidine vs sigma receptors. Compounds that act on phencyclidine receptors, as well as affecting behavior, alter body temperature in the rat. The purpose of the present study was to compare and contrast the effects of the acute administration of dexoxadrol, levoxadrol, MK-801 and phencyclidine on body temperature in the rat. Dexoxadrol and levoxadrol (5.0, 10.0, 20.0 or 40.0 mg/kg), MK-801 (0.12, 0.6 or 1.2 mg/kg) or phencyclidine (5.0, 10.0 or 20.0 mg/kg) were administered subcutaneously and body temperature was measured. Both dexoxadrol and MK-801 produced hyperthermia but levoxadrol did not affect body temperature. In contrast to the hyperthermic effects of dexoxadrol and MK-801, phencyclidine produced hypothermia. These findings indicate that hypothermia induced by phencyclidine is not due to interactions with phencyclidine receptors and, while dexoxadrol, MK-801 and phencyclidine may share some similar receptor binding and behavioral characteristics, they can be differentiated on the basis of their effects on body temperature.

Animals↗