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Biomedical subjects

J D Stewart

Publications and source records attributed to J D Stewart.

At least 73 records · Page 4Linked to original sources

Characterization of the in vitro unscheduled DNA synthesis assay in primary lung cells of the rat.

The in vitro unscheduled DNA synthesis (UDS) assay has been evaluated in rat primary lung cells with known genotoxicants. The autoradiographic method was employed to detect UDS in both alveolar macrophages and primary pulmonary cells. Data of a time course study revealed that a high radioactive labeling of DNA repair was achieved after a 16-h incubation with [3H]thymidine. Coupled with low serum (1%), hydroxyurea at the concentration of 20 mM inhibited regular DNA synthesis in primary lung cells in a satisfactory manner (81-88% inhibition). With this protocol, a dose-related increase in UDS was induced by N-methyl-N'-nitro-N-nitrosoguanidine and 2-aminoanthracene in both rat alveolar macrophages and primary lung cells. The results suggest that primary rat lung cells in culture possess DNA-repair ability and that the UDS assay may be useful for assessing the pulmonary genotoxic effect of chemicals in this cell system.

Animals↗

Common peroneal neuropathy: A study of selective motor and sensory involvement.

We performed a prospective clinical and electrophysiologic study of common peroneal (CP) neuropathy to evaluate the extent of involvement of the muscles and cutaneous areas supplied by this nerve. In 22 patients, seven had more weakness clinically in muscles innervated by the deep peroneal nerve than in those innervated by the superficial peroneal nerve; the reverse never occurred. Statistical paired comparisons confirmed the tendency in the entire group of patients for weakness to be greater in muscles supplied by the deep peroneal nerve. On EMG, denervation was more often present and of more marked degree in muscles supplied by the deep peroneal nerve. Motor nerve conduction studies indicated axonal damage and focal demyelination with similar frequency. Sensory deficits varied in the three areas supplied by the cutaneous branches of the CP nerve: five patients had involvement of all three areas, 11 of two areas, two of one area, and four had no sensory deficit. The most likely explanation for these findings is differing degrees of damage to individual fascicles within the CP nerve.

Adolescent↗

Effect of bromocriptine in patients with apomorphine-responsive erectile impotence: an open study.

An open pilot study was undertaken to investigate the therapeutic effect of the dopaminergic agent, bromocriptine (BC), in impotent patients who developed an erectile response to the dopamine receptor agonist, apomorphine. Eight out of 17 patients reported improvement in ability to obtain an erection; five of these 8 subjects were able to achieve penetration. The optimum dose of BC was 2.5 - 11.25 mg/day. A double-blind placebo-controlled study is merited.

Adult↗

Use of rat primary lung cells for studying genotoxicity with the sister-chromatid exchange and micronucleus assays.

Primary culture of lung cells from CD rats was established for pulmonary genotoxicity studies using two genetic endpoints, sister-chromatid exchange (SCE) and micronucleus formation (MN). In the cell isolation study, a combined enzyme separation of rat lungs with trypsin (1.3 mg/ml) plus collagenase (50 U/ml) gave the highest yield of viable and colony-forming cells. For the MN assay, the cytokinesis block induced by cytochalasin B (CYB) was employed to enumerate MN in binucleated (BN) cells. Treatment of primary lung cells with 2 micrograms CYB/ml for two days appeared to be optimal for scoring micronuclei in CYB-induced BN cells. By this procedure, mitomycin C (MMC), triethylenemelamine, and benzo[a]pyrene caused a dose-related increase in micronucleated BN cells in vitro without metabolic activation. In the SCE assay, maximum second-division metaphases were obtained after cells were incubated with bromodeoxyuridine for 48-54 h. After this incubation time, high frequencies of SCE induced by MMC and 3-methylcholanthrene after in vitro exposure (without S9 activation) or in vivo exposure were observed. The results indicate that rat primary lung cells can metabolize polycyclic aromatic hydrocarbons and that this lung cell system is potentially useful for the detection of pulmonary genotoxicants.

Animals↗

A syndrome of asymmetric limb weakness with motor conduction block.

We describe 3 patients with asymmetric limb weakness, fasciculations (2 patients), relatively preserved reflexes, normal cranial nerves, and few or no sensory abnormalities. The symptoms had been progressive over 1 to 15 years. Detailed motor nerve conduction studies showed conduction block and slowing localized to sharply circumscribed areas 30 to 100 mm long in several nerves in each patient. By contrast, the sensory conduction studies over the same nerve segments were normal, indicating very selective involvement of motor fibers. Sural nerve biopsies showed minor changes that varied among the patients. One patient had high levels of anti-GM1 antibodies, 1 had mildly elevated levels, and 1 had high levels of only asialo-GM1 antibodies. Treatment with immune suppressive therapy has produced minimal improvement in 1 patient.

Electrophysiology↗

Use of bacterial assay system for monitoring genotoxic complex mixtures in the occupational setting.

Workplace environmental genotoxicity assessments, which may be carried out either by laboratory analysis or using an in-situ assay system, are potentially useful for health hazard evaluations, for industrial hygiene and biological (genetic) monitoring. Whenever possible, genotoxicity assays should be performed in conjunction with industrial hygiene studies to assess the biological activity of workplace contaminants. Efforts should continue to be made to establish a simple and reliable in-situ assay system for the detection and monitoring of genotoxic complex mixtures in the occupational setting.

Animals↗

Diabetic truncal neuropathy: topography of the sensory deficit.

The distributions of sensory abnormalities in 17 episodes of diabetic truncal neuropathy among 7 patients with diabetes mellitus are described. The patterns are highly variable: the distribution of adjacent main spinal nerves may be involved, resulting in a complete dermatomal band of dysesthesia, but almost two-thirds of the episodes were restricted to the distribution of the ventral or dorsal rami of the spinal nerves or branches of these rami or varying combinations of these distributions.

Aged↗

Auditory agnosia: apperceptive or associative disorder?

Neuropsychological testing of a patient with auditory agnosia showed that certain difficulties in the initial analysis of sounds may be the cause of his inability to understand spoken words and other sounds. Abnormalities included a slow reaction time to brief auditory stimuli (but not to equally brief visual stimuli or to longer auditory stimuli) and the need for approximately 1/4 sec of silence between two tones before the patient was able to hear them as separate. He could identify words and word associations if he was able to view the object whose name or word associate he was hearing. The findings imply that this patient's deficit in comprehending speech was probably apperceptive rather than associative in origin.

Agnosia↗

Comparative antimutagenicity of 5 compounds against 5 mutagenic complex mixtures in Salmonella typhimurium strain TA98.

Using the Ames Salmonella/microsome assay, we compared the antimutagenic activities of chlorophyllin, retinol, beta-carotene, vitamin C, and vitamin E against solvent extracts of coal dust, diesel emission particles, airborne particles, fried beef, and tobacco snuff. The results show that chlorophyllin inhibited 69% of the mutagenic activity of tobacco snuff and over 90% of that of the other 4 complex mixtures. Retinol inhibited 29-48% of the mutagenic activity of all 5 complex mixtures. beta-Carotene, vitamin C, and vitamin E inhibited, if any, less than 39% of the activity of the complex mixtures studied. Vitamin C enhanced the mutagenicity of airborne particles. These results indicate that for these dietary and environmental complex mixtures chlorophyllin is a more effective antimutagen than retinol, beta-carotene, vitamin C, and vitamin E.

Air↗

Genotoxicity and genotoxic enhancing effect of tetrandrine in Salmonella typhimurium.

Tetrandrine has been used for the treatment of silicosis in China. The potential genotoxic and carcinogenic hazards of this drug were studied using the Salmonella/histidine reversion assay and the SOS/Umu test. The results show that tetrandrine was weakly mutagenic to Salmonella typhimurium TA98 with metabolic activation and did not induce SOS response. However, tetrandrine increased the mutagenic activity of benzo[alpha]pyrene, trinitrofluorenone (TNF), 2-aminoanthracene (2AA), diesel emission particles, airborne particles, and cigarette smoke condensate by more than 100%; the activity of aflatoxin B1 and fried beef was increased by over 75%. It also increased the 2AA and TNF-induced SOS response by more than 300%. These results indicated that tetrandrine was a weak promutagen inducing frameshift mutations and was a potent genotoxic enhancer. The mechanism for the genotoxic enhancement is not known. However, the fact that the increase in mutagenicity was noted only in TA98 and not in TA1538 suggested that the enhancement of genotoxicity by tetrandrine may result from an increase in error-prone DNA repair.

Alkaloids↗

Distal sciatic nerve compression by a popliteal artery aneurysm.

A 77-year-old man developed progressive sensory and motor symptoms in the right lower leg. Examination showed neurological deficits in the distribution of the right tibial and common peroneal nerves. Swellings in both popliteal fossae were palpated. Investigation showed these to be large thrombosed aneurysms. On surgical examination on the right, the aneurysm was found to be compressing the distal sciatic nerve.

Aged↗

Interferon induction inhibition and mutagenic activity of nitrosated coal dust extract.

Specified cytotoxicity and mutagenicity of coal dust extract (mixture of solvent extractions of bituminous coal nitrosated by NaNO2) were investigated because of the association of an excess risk of gastric cancer in coal miners. The effect of nitrosated coal dust on a cellular defense component of the interferon system, the induction of interferon (alpha/beta) in mammalian cell cultures by influenza virus, and mutagenicity, using the Salmonella/microsome assay, were determined. Nitrosated coal dust extract contained both bioactivation-independent and -dependent (microsome enzymatic activation) compounds that significantly inhibited the viral induction of interferon by greater than 50%. Nitrosated extract was mutagenic but exhibited no increase in mutagenic activity in the presence of microsomal enzymes. With further extraction of nitrosated coal dust extract by horse serum and fractionation thereof, the soluble chemical complexes formed with fractions of high molecular weight without bioactivation were dominant in both mutagenicity and inhibition of interferon induction. Low-molecular-weight fractions, with or without a metal chelator, and with or without bioactivation, all inhibited interferon induction comparably and significantly. There was no mutagenic activity manifested by these serum fractions. Metal-serum complexes were either not formed, or, if present, were ineffectual according to the biologic criteria employed. The findings of this study are discussed in terms of the association between nitrosated coal dust and gastric carcinogenesis.

Animals↗

Drug-induced modifications of the immune response. 12. 4,5-Dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids and derivatives as novel antiallergic agents.

The synthesis of a series of novel 4,5-dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids, salts, esters, and amides is described. The title compounds when tested in the mediator-induced dermal vascular permeability and active anaphylaxis assays in rats demonstrated moderate to potent antiallergic activity. The [2-trans-(4-methylphenyl)cyclopropyl]amino analogue 53 emerged as the most active derivative. Thus, when administered intraperitoneally to rats at a dose of 100 mg/kg, it inhibited the action of the mediators serotonin, histamine, and bradykinin by 100%. In the active anaphylaxis assay in rats, compound 30 suppressed the edema by 81% at a dose of 100 mg/kg, following intraperitoneal administration.

Animals↗

Is the message getting through? Nutritional knowledge of pregnant women in Edinburgh and London.

This paper reports the results of a survey in which pregnant women in London and Edinburgh were asked about their knowledge and understanding of the recent recommendations of expert committees (James, 1983; DHSS, 1984). In general, Londoners had a better understanding, although in both regions manual groups were less knowledgeable, with the Edinburgh manual group the least well informed.

Adolescent↗

Acid-mediated mutagenicity of tobacco snuff: its possible mechanism.

Polar solvent extracts of tobacco snuff under acidic conditions were mutagenic in Salmonella typhimurium. Using the Griess reagent test, nitrite ranging from approximately 1.8 to 5.4 mg/g of snuff was found in the polar fraction of extracts. After acid treatment, nitroso compounds in the amount corresponding to the nitrite concentration were detected. The mutagenic potency of the acid-treated extracts was consistent with the content of nitroso compounds generated. Formation of nitroso compounds and the mutagenic activity under acidic conditions was inhibited by ascorbic acid. The results indicate that a nitrosation process was involved in snuff extracts during acid treatment. Studies related to the source of nitrite in tobacco snuff demonstrated that snuff contained bacteria which were able to reduce nitrate to nitrite and that the amount of nitrite in snuff extracts could be further increased by incubation of the extracts with the bacteria. Since snuff contains a considerable amount of nitrate, it seems that reduction of nitrate in snuff to nitrite by bacteria, and nitrosation of certain constituents in snuff by nitrite under acidic conditions to form mutagenic nitroso compounds are possible mechanisms responsible for the acid-mediated mutagenicity of snuff extracts.

Ascorbic Acid↗