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Biomedical subjects

R A Wall

Publications and source records attributed to R A Wall.

70 records · Page 4Linked to original sources
PubMed1984

Metabolic fate of (E)-5-(2-bromovinyl)-2'-deoxyuridine in herpes simplex virus- and mock-infected cells.

(E)-5-(2-Bromovinyl)-2'-deoxyuridine is a potent antiherpes compound with far better activity against herpes simplex virus type 1 than type 2. To understand the role of drug metabolism in this differential antiviral activity, we examined the metabolic fate of this drug in virus-infected and mock-infected Vero cells by high-pressure liquid chromatography. After 8 h of incubation in which cells were exposed to 10 micrograms of the drug per ml, 63 pmol/10(6) cells of the parent compound was detected in acid-soluble extracts of mock-infected cells. Herpes simplex virus-infected cells, however, incorporated or metabolized, or both, up to 11,310 pmol/10(6) cells. Type 1-infected cells metabolized the drug to the triphosphate where as many as 5,565 pmol/10(6) cells were detected. In contrast, three strains of type 2-infected cells metabolized the drug to the monophosphorylated nucleotide and no further. The amount of drug getting into the cells was virus strain and inoculum dependent. These studies indicate that poor substrate acceptance of (E)-5-(2-bromovinyl)-2'-deoxyuridine monophosphate by herpes simplex virus type 2-specified thymidylate kinase is an important factor in situ in infected cells, preventing anabolism of the parent compound to its active triphosphorylated form. This may account for its type specificity.

Antiviral Agents↗
PubMed1982

Human CSF GABA concentrations: revised downward for controls, but not decreased in Huntington's chorea.

gamma-Aminobutyric acid (GABA) concentrations were measured in CSF specimens from two large groups of control subjects, one without neurological or psychiatric disease, and one with a variety of neurological disorders not known to involve altered GABAergic function in brain. CSF GABA was also measured in patients with Huntington's chorea and in patients with other choreiform disorders. GABA was measured in CSF by a modification of the ion exchange-fluorometric method that featured use of a relatively large cation exchange column, and a markedly decreased quantity of sulfosalicylic acid for deproteinization of CSF. Mean BABA concentrations in CSF were 87 and 77 nmol/liter for neurologically normal and abnormal control subjects, 82 nmol/liter for the Huntington's chorea patients, and 105 nmol/liter for patients with other forms of chorea. The mean concentration of homocarnosine was not reduced in CSF of Huntington's chorea patients as compared with controls. Mean CSF GABA concentrations found in control subjects were less than half the lowest control means previously reported. These low values are attributable in part to a reduction in on-column hydrolysis of conjugated forms of GABA in CSF, which can be produced by excessive sulfosalicylic acid, and in part to improved chromatographic resolution of GABA from other unknown o-phthalaldehyde-reactive compounds in CSF. Analysis of free GABA in CSF does not appear useful for diagnosis of suspected Huntington's chorea, nor as a possible predictive test for persons genetically at risk for Huntington's chorea.

Carbon Radioisotopes↗
PubMed1982

Comparison of ELISA, SPACE, and electron microscopy for the routine diagnosis of rotavirus infection.

Previous studies on the serological diagnosis of rotavirus infection have utilised locally produced antibodies. In this study we have compared two commercially produced assays, an ELISA (Rotazyme, Abbott) and a newly developed assay--solid phase aggregation of coupled erythrocytes (SPACE) (Wellcome Research Laboratories), with electron microscopy (EM). The SPACE test appeared less sensitive than EM. The ELISA was shown to be as sensitive as EM but more versatile. Our experience suggests that the ELISA could be successfully incorporated into the routine of any diagnostic laboratory.

Enzyme-Linked Immunosorbent Assay↗
PubMed1981

Elevation of brain GABA content by chronic low-dosage administration of hydrazine, a metabolite of isoniazid.

When gamma-aminobutyric acid aminotransferase (GABA-T) activity was measured in vitro in rat brain, neither isoniazid (INH) nor for of its known metabolites (isonicotinic acid, acetylisoniazid, acetylhydrazine, diacetylhydrazine) inhibited the enzyme in concentrations (5 mM) far higher than those likely to be achieved when INH is administered to man. In contrast, hydrazine (5 micrometers) caused a 50% inhibition of GABA-T without inhibiting glutamic acid decarboxylase (GAD). Rats were injected daily for 109 days with hydrazine (0.08 or 0.16 mmol/kg/day), after which amino acid contents and enzyme activities were measured in their brains. Both hydrazine doses caused significant elevations of whole brain GABA content and reductions of GABA-T activity, but did not affect GAD activity. Chronic administration of hydrazine at these doses did not reduce weight gain or alter rat behavior, nor did it produce any irreversible pathologic changes in liver or alterations in hepatic aryl hydrocarbon hydroxylase activity. However, hydrazine treatment caused changes in the contents of many brain amino acids besides GABA, and markedly increased concentrations of ornithine, tyrosine, and alpha-aminoadipic acid in rat plasma. Inhibition of GABA-T activity and the other biochemical alterations observed in patients given high doses of INH probably result from hydrazine formed in the metabolic degradation of INH. Thus administration of hydrazine might be a more direct means of elevating brain GABA content in patients where this seems indicated, and might not entail a greater risk of adverse effects.

4-Aminobutyrate Transaminase↗
PubMed1981

Gonococcal septicaemia presenting as a subcutaneous abscess.

In a case of disseminated gonococcal infection the diagnosis was delayed until Neisseria gonorrhoeae was grown from pus from a discharging abscess of the biceps muscle. This unusual skin manifestation appears not to have been reported before.

Abscess↗
PubMed1977

Painful ophthalmoplegia.

A syndrome of acute periorbital pain, followed by the onset of ophthalmoplegia, has, in recent years, been recognised as a distinct entity. Six patients conforming to this clinical picture are presented from Zambia, and the characteristics of the syndrome is described. Attention is drawn to the existence of the condition in Arica and to its dramatic improvement with systemic steroid treatment. Particularly in those areas with limited investigatory facilities, the use of steroids can constitute a therapeutic test.

Adult↗
PubMedDate not supplied

Chronic ethanol consumption, stress, and hypertension.

A reliable method of producing physical stress in the rat was developed using heat irradiation, and the possible interaction between chronic ethanol consumption and stress was investigated in a rat model of alcoholism. Chronic heat stress and chronic ethanol consumption each produced mild hypertension in rats. When combined, the two treatments resulted in hypertension more severe than that produced by either stress or ethanol consumption alone. The group of animals receiving both treatments also exhibited high mortality. Investigations into the mechanisms responsible for the apparent additive effects of the two treatments revealed that the animals in this group had the highest circulating norepinephrine levels. The plasma volumes, however, were not different between the stressed groups and their unstressed counterparts. As the plasma norepinephrine level usually reflects overall sympathetic tone of an animal, our results suggest that the additional hypertensive effect of chronic stress on the ethanol-treated animals is associated with increased sympathetic nervous activity and is not a result of expanded plasma volume. These findings may have clinical implications for human alcoholics and in the analysis of cardiovascular risk factors in hypertensive patients.

Alcoholism↗
PubMedDate not supplied

The acute and chronic effects of nitrendipine on plasma catecholamines in hypertensive patients.

OBJECTIVE: To investigate the acute and chronic effects of nitrendipine on plasma catecholamines in hypertensive patients. DESIGN: The variations in level of plasma noradrenaline and adrenaline were measured in the supine and standing positions before and after the initial dose, and after 12 weeks of nitrendipine therapy. Following a washout placebo period, treatment was initiated by a single 20 mg dose of nitrendipine. This was followed by a double-blind randomization into two groups: one receiving 10 mg nitrendipine twice daily, the other receiving 20 mg once daily. SETTING: Clinical investigation unit, University Hospital (University of British Columbia site), Vancouver, British Columbia. PATIENTS: Sixteen patients (seven males and nine females), mean age 51 years (range 27 to 63), with mild to moderate, uncomplicated hypertension. RESULTS: Two hours after administration of the initial 20 mg nitrendipine dose to all patients, there was a significant fall in the supine and standing systolic and diastolic blood pressure - from 164 +/- 3/102 +/- 1 to 139 +/- 2/87 +/- 2 mmHg, and from 153 +/- 4/105 +/- 1 to 139 +/- 3/90 +/- 1 mmHg, respectively. The supine and standing heart rates were unchanged. After 12 weeks of nitrendipine therapy, blood pressure was reduced (2 h after the dose) to a similar extent as that seen after the initial dose. Acute and chronic nitrendipine administration significantly increased supine and standing noradrenaline, but not adrenaline. Two hours after the initial 20 mg dose, supine noradrenaline increased from 3404 +/- 585 to 4005 +/- 644 pmol/L and standing noradrenaline increased from 3769 +/- 609 to 5821 +/- 615 pmol/L. At the end of the 12 weeks of therapy, similar dose-dependent effects were observed 2 h after the dose, but not 12 or 24 h after the dose, in both groups. The percentage increase in noradrenaline produced by nitrendipine in the standing position was consistently greater than in the supine position. CONCLUSIONS: Chronic nitrendipine therapy results in a daily increase in plasma noradrenaline (2 h after the dose), and the effect is greater in the standing position.

Blood Pressure↗