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Biomedical subjects

T A Smith

Publications and source records attributed to T A Smith.

At least 127 records · Page 7Linked to original sources

Respiratory infections in coal miners exposed to nitrogen oxides.

Coal miners working underground may be exposed chronically to low levels of nitric oxide and nitrogen dioxide from diesel engine emissions and from the use of explosives for blasting. The aims of this study were to establish whether long-term exposures to low concentrations of these gases at nine British coal mines had been associated with increased susceptibility to respiratory infections and, if so, to estimate the relative risks for different levels of exposure. The nine mines concerned had been involved, since 1954, in a prospective epidemiological study of coal miners' health. Median levels of nitrogen oxides in 4,933 pairs of full-shift samples, taken at the mines during the years 1976 through 1982 were 0.2 ppm nitric oxide and 0.03 ppm nitrogen dioxide; 10 percent of the concentrations exceeded 1.1 ppm nitric oxide and 0.08 ppm nitrogen dioxide. Multiple regression estimates of concentrations associated with different underground locations, types of work, and mining conditions at each mine were combined with detailed records of miners' attendance at work at similar locations in earlier years. These retrospective estimates of individuals' underground exposures to nitrogen oxides referred to between five- and 16-year periods of exposure. Also available for study were records of the men's exposures to respirable mine dusts and information from five-yearly medical surveys about their smoking habits, respiratory symptoms, and questionnaire-elicited reports of sickness absences attributed, among other things, to respiratory infections. The reliability of the latter reports was examined in a sample of 471 of the men by comparing the answers to the questionnaire with physicians' diagnoses on certified sickness absence records. Miners' references to bronchitis, influenza, or colds as the cause of prolonged sickness absence during the three years preceding the surveys did, in general, reflect real spells of absence from work, lasting at least seven days, that had been diagnosed by doctors as due to respiratory infections. But only about 20 percent of the men whose colliery records indicated that there had been such an absence acknowledged them in the survey as due to a "chest illness". Most of the under-reporting was of absence certified as due to influenza, colds, or "upper respiratory tract infection", and this under-reporting was not related to the men's ages or smoking habits. The main analyses referred to 5,408 reports of colds, influenza, or bronchitis at a total of 40,071 interviews involving nearly 20,000 miners.(ABSTRACT TRUNCATED AT 400 WORDS)

Absenteeism↗

DNA repair in lymphocytes from young and old individuals and from patients with Alzheimer's disease.

Lymphocytes from patients with ataxia telangiectasia and Down's syndrome show a greater frequency of chromosome aberrations after ionising radiation than do lymphocytes from normal people. The connection between Down's syndrome and Alzheimer's disease (AD) is well-known. In view of this and of a study showing a greater sensitivity of AD than of normal lymphoblastoid cells to X-irradiation (measured by viability), we have examined repair of AD lymphocytes (hydroxyurea-treated) by measuring [3H]thymidine incorporation after gamma-irradiation. We have found no difference in incorporation between AD and normal lymphocytes from age-matched individuals. However, incorporation decreases with age in gamma-irradiated cells and to a lesser extent in unirradiated cells.

Adult↗

Clones defective in metabolic cooperation selected from a pluripotent feeder-dependent mouse embryonal carcinoma cell line.

Starting from embryonal carcinoma (e.c.) cells capable of extensive differentiation in culture, the technique of thioguanine 'kiss of death' has been used to select four independent metabolic cooperation-defective variants. The communication ability of these variant cell lines has been quantified by autoradiographic measurement of the transfer of uridine nucleotides, and also by an assay of the extent of junction-mediated rescue from ouabain toxicity by resistant fibroblasts. The cell lines which are defective in ability to transfer nucleotides, as measured by the uridine nucleotide transfer assay, are also defective in their ability to differentiate into endoderm and to form the cavitated 'embryoid bodies' which are produced by the parental cell line when grown in suspension culture. However, it is not clear whether this is related to the defects in metabolic cooperation, since clones which had been subjected to the same selective conditions but which cooperate normally have also lost some of the capacity to undergo this differentiation. Endoderm differentiation was classified into two categories, one being visceral endoderm and the other, primary plus parietal endoderm, on the basis of morphology, immunocytochemical staining for alpha-fetoprotein, and basement membrane formation. With the exception of correlations arising from variations between experiments and differences between cell lines, there is no statistical association between these two categories of differentiation. The formation of cavities was observed only in embryoid bodies with endoderm differentiation: the present of either category was a sufficient condition for cavitation to occur.

Animals↗

Selection of a mouse embryonal carcinoma clone resistant to the inhibition of metabolic cooperation by retinoic acid.

A novel selection for cell lines resistant to the blocking of metabolic cooperation by chemical inhibitors is described. The selection has been used to isolate a pluripotent embryonal carcinoma clone which cooperates in retinoic acid (RA), an inhibitor of junctional communication in all other cell lines tested to date. The selected cells require higher levels of RA to induce differentiation, but show little or no increase in resistance to toxic effects of RA.

Animals↗

Growth cones of developing retinal cells in vivo, on culture surfaces, and in collagen matrices.

The outgrowth of axons from the early retina in vivo is compared with that from retinal explants in two types of culture systems. The normal time course of axonal growth along the primordial optic pathway to the optic tectum is characterized, using tritiated proline and horseradish peroxidase (HRP) as anterograde tracers. The rate of axonal elongation in vivo is estimated to be about 32 micron/hr at 22 degrees C. The HRP technique allows visualization of retinal growth cones in vivo. Observations can thus be made on their microanatomy and on the environment through which they navigate. The growth cones of retinal ganglion cells in the embryo have lamellipodia and fairly short filopodia (approximately 10 micron) which are directed forward. The growth cones are found near the pial surface of the brain but do not seem to maintain contact with it. Two culture systems were developed to investigate axonal pathways in vitro. In the first, different substrates and culture media were explored. Results indicate that growth cones prefer a polyornithine substrate over a collagen one. The media that promotes the best neurite outgrowth consists of L15 (60%), fetal calf serum (10%) and Xenopus embryo extract (1 mg/ml). Time-lapse video monitoring of substrate cultures reveals an average rate of outgrowth of about 18 micron/hr with great variability. The growth cones in these cultures are large, flattened, and complex compared to those in vivo, and their filopodia extend in many different directions. The second culture system is a collagen gel infiltrated with growth medium. In these conditions neurite outgrowth more closely mimics that in vivo. The rate is faster than on substrates, and the growth cones appear morphologically similar to those in the embryo. Preliminary experiments using the gel culture system to test for chemotaxis of retinal axons toward their targets failed to demonstrate such an effect.

Animals↗

Repair and recombination of nonreplicating UV-irradiated phage DNA in E. coli II. Stimulation of RecF-dependent recombination by excision repair of cyclobutane pyrimidine dimers and of other photoproducts.

Three aspects of recombination of UV-irradiated nonreplicating lambda phage DNA were addressed: the photoproduct(s) responsible, the role of UvrABC-mediated excision repair, and the dependence on RecF function. Cyclobutane pyrimidine dimers appeared responsible for some recombination because photoreactivation reduced the frequency of 254-nm-stimulated recombination and because photosensitized 313-nm irradiation stimulated recombination. Other photoproducts seemed recombinogenic as well, because high fluences of 254-nm irradiation stimulated recombination considerably more, per cyclobutane dimer induced, than photosensitized 313-nm irradiation, and because photoreactivation did not eliminate 254-nm stimulated recombination. For both treatments, much, but not all, of the recombination was UvrABC-dependent. Recombination was mostly RecF-dependent, but was not affected by recB recC or recE mutations

Bacteriophage lambda↗

A three-frequency audiogram for use in industry.

Some form of audiometric screening forms part of any comprehensive hearing conservation programme, but because of the large numbers of workers exposed to noise, it is suggested that routine audiometry using an 8-frequency test preceded by history and examination makes undue demands on limited resources. It is proposed that a simple 3-frequency test without prior preparation of subjects is adequate for the purposes of industrial audiometry. Men whose hearing threshold was worse than 20 dB at 1, 2, or 4 kHz were considered to have failed the 3-frequency test and 150 such cases were randomly selected and subjected to a full 8-frequency audiogram. The results were then assessed for numerical accuracy and diagnostic reliability. The results of the 3-frequency test were marginally worse than the 8-frequency audiogram by 2.33 to 4.98 dB, and the comparison of the two tests as a diagnostic tool gave a concordance rate of 79%-80% (p = 0.00001) between the two physicians who examined the results and a level of interpersonal agreement of 87% for the 3-frequency test and 89% for the full audiogram. If audiometric screening is to be offered to the whole population at risk it should be simple, rapid, and accurate enough to detect hearing loss before disability develops so that those individuals may be counselled. It is suggested that the 3-frequency test fulfils this purpose, demonstrates the "reasonably practicable" approach of recent legislation, and does not unnecessarily divert resources from other key tasks in the practice of occupational medicine.

Audiometry↗

Medium conditioned by feeder cells inhibits the differentiation of embryonal carcinoma cultures.

Non-dividing STO mouse fibroblasts have been used for some time as feeder cells for maintaining certain embryonal carcinoma cells in an undifferentiated state. We report here that medium conditioned by these feeders can inhibit embryonal carcinoma (ec) cell differentiation induced either by removal from feeders, or, in the case of cells not normally requiring a feeder layer, by retinoic acid treatment.

Animals↗

Hyponatremia in patients with schizophrenia.

Although there is a definite association between hyponatremia and schizophrenia, the true incidence and etiology have not been established. This report is a retrospective study of all admissions to the Baroness Erlanger Hospital over a three and one-half year period. There was a 5.8% incidence of hyponatremia in patients with schizophrenia as compared with a 0.36% incidence for all admission (P less than .01). Schizophrenic patients at risk for developing hyponatremia drank water excessively(P less than .01) and were most likely to be taking thioxanthene (P = .05(4)) antipsychotic and anticholinergic medications (P Less than .01). Most schizophrenic patients admitted with hyponatremia had dangerously low serum sodium levels (less than or equal to 120 mEq) and showed severe neurologic dysfunction. This retrospective study compares the clinical features of schizophrenic patients who develop hyponatremia and those who do not. The possible role of antidiuretic hormone is discussed

Adult↗

Sleep apnea and Q-T interval prolongation--a particularly lethal combination.

We have discovered a 20-day-old infant who possessed anatomic evidence of chronic hypoxemia with right ventricular hypertrophy and who died in hypoxic hypoxemia with a postmortem PO2 of 4 mm. Hg. Subsequently, and ECG was discovered which had been obtained at one day of age and showed Q-T interval prolongation along with T-wave alternation. We believe this case to be one of the first to substantiate the mechanism for SIDS as proposed by Schwartz, 26 with hypoxia acting synergistically with a prolonged Q-T interval causing sudden unexpected death in this infant--providing a link between cardiac and respiratory mechanisms of death.

Adult↗