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Biomedical subjects

A N Jha

Publications and source records attributed to A N Jha.

14 recordsLinked to original sources

The polychaete Platynereis dumerilii (Audouin and Milne-Edwards): a new species for assessing the hazardous potential of chemicals in the marine environment.

The polychaete Platynereis dumerilii (Polychaeta: Nereidae) has been evaluated as a candidate bioassay species for marine ecotoxicity testing. The species conforms with many of the requirements of an ideal bioassay organism in that (i) it is amenable to laboratory culture, (ii) its relatively small size makes it convenient for handling and laboratory exposure studies, (iii) its diet is defined and can be controlled, (iv) it reproduces throughout the year and, using photoperiod manipulation, can be induced to spawn as required, and (v) it has a short life cycle (approximately 3 months at 20 degrees C) making it feasible to study the effects of xenobiotics on chronic endpoints such as reproduction. The components of the life history which have been examined to date include fertilization rate, embryo-larval development, and larval survival. These life stages were evaluated using the reference materials used in the 1991 International Paris Commission (PARCOM) Ring Test (namely, the biocides, Bioban P-1487 and Vantocil IB, and the widely used reference toxicant, 3,5-dichlorophenol). For fertilization rate, the median effect concentrations (1-h EC50 values) were 0.32 mg.liter-1 for Bioban P-1487, 1.92 [corrected] mg.liter-1 for 3,5-dichlorophenol, and 9.66 mg.liter-1 for Vantocil IB. For embryo-larval development, the median effect concentrations (48-h EC50 values) were 0.29 mg.liter-1 for Bioban P-1487, 2.13 mg.liter-1 for 3,5-dichlorophenol, and 4.81 mg.liter-1 for Vantocil IB. For larval survival, the median lethal concentrations (48-h LC50 values) were 0.32 mg.liter-1 for Bioban P-1487, 3.64 mg.liter-1 for 3,5-dichlorophenol, and 10.9 mg.liter-1 for Vantocil IB. These results (all based on nominal values) suggest that, for these reference materials, the early life stages of P. dumerilii are of similar sensitivity to other marine invertebrate species. Together with the amenability of this species to laboratory culture, these data suggest that P. dumerilii has significant potential for use in marine ecotoxicity testing.

Animals

Ionizing radiation induced DNA lesions which lead to chromosomal aberrations.

Several radiosensitive mutant cell lines of CHO and V79 cells have been studied to explore a possible correlation between radiation induced DNA lesions and chromosomal aberrations. In the xrs mutants which are deficient in DNA double strand break (DSB) repair, there is a correlation between the extent of the defect in repair and the frequencies of radiation induced chromosomal aberrations. In another type of radiosensitive mutant (V-C4), which has no detectable defect in DNA DSB repair, the frequencies of X-ray induced aberrations are high in comparison to wild type V79 cells. However, following treatment with restriction endonucleases or fission neutrons, the frequencies of aberrations are similar to those in V79, indicating that V-C4 cells are defective in repair of X-ray induced lesions other than DSBs. Though DSBs are the most important lesions leading to chromosomal aberrations, in repair deficient mutants, radiation induced lesions other than DSBs can lead to chromosomal aberrations.

Animals

Genotoxic effects of sodium arsenite on human cells.

The effects of sodium arsenite (SA) were studied either alone or in combination with X-rays in peripheral blood lymphocytes, and with short-wave ultraviolet (UV) radiation in primary human fibroblast culture systems. It was found that SA (i) inhibited the cell cycle progression of phytohaemagglutinin (PHA)-responsive lymphocytes, (ii) induced chromatid-type aberrations and sister-chromatid exchanges (SCEs) as a function of concentration and (iii) potentiated the X-ray- and UV-induced chromosomal damage. Our results suggest that SA interferes with the DNA repair process, presumably by inhibiting the ligase activity. This accounted for an increase in the DNA replication-dependent processes, chromatid aberrations and SCEs and synergistic enhancement of the X-ray- and UV-induced chromosomal damage. This ability of arsenite may be responsible for its comutagenic properties with different types of mutagens and hence its carcinogenicity.

Arsenic

Effect of storage duration on cell cycle kinetics and yield of chromosomal aberrations in PHA-responsive human peripheral blood lymphocytes.

Phytohaemagglutinin (PHA)-responsive lymphocytes from human peripheral blood samples, either irradiated or un-irradiated, showed increased frequency of first division metaphase cells (detected by fluorescence plus Giemsa (FPG) staining) as a function of duration of storage. Irradiated and subsequently stored samples showed small but significant increase for the yield of dicentrics. The yield of aberrant metaphases and deletions (excess acentrics) remained unchanged. Increasing Bromodeoxyuridine (BrdU) concentrations slowed down the cell cycle progression but did not influence the yield of aberrations including that of dicentrics.

Analysis of Variance

Relative ranking of culture media based on proliferation kinetics and spontaneous chromosomal aberrations in PHA-responsive human peripheral blood lymphocytes.

Proliferation kinetics and spontaneous yield of chromosomal aberrations phytohemagglutinin (PHA)-responsive peripheral blood lymphocytes were studied from blood samples collected from 45 individuals in 4 different synthetic media. Except for a significant difference for Eagle's MEM and RPMI 1640, the other media did not show difference for the yield of chromatid or chromosome type of aberrations. Differences were however noticed in the proliferation kinetics (mitotic and proliferative rate indices) of cells among the media used. The study indicated that (i) the intrinsic properties of media which influence proliferation rate and yield of chromosomal aberrations are independent of each other as higher proportion of first division cells do not correspond with higher frequency of chromosomal aberrations, (ii) the amount of free-radical scavengers present in the medium, apart from the genetic make-up of the individuals, may contribute to the spontaneous yield of chromosomal aberrations and (iii) RPMI 1640 medium, which showed higher transformation and faster cycling rate for the lymphocytes, may be considered as medium of choice for analysing two main cytogenetic end-points, chromosomal aberrations and sister chromatid exchanges (SCEs).

Adolescent

Distribution pattern and dose-response-relationship of chromosome aberrations in human lymphocytes induced in vitro by 60Co gamma-rays and 110 kV X-rays.

Peripheral blood lymphocyte culture system was used to construct reference dose-response curves for 60Co gamma-rays and 110 kV X-ray-induced chromosome aberrations at 6 dose points ranging from 0.25 to 4.0 Gy. Qualitative and quantitative differences between these two types of radiation for the yield of induced aberrations and their distribution pattern were analysed. Experimental data of aberration yields were compared after fitting them to five different dose-response models. The yields of chromosome aberrations in particular dicentrics, gave a good fit to linear-quadratic besides linear and power models. In this model, single-track events predominated over double-track events for both the qualities of radiation used. The pattern of distribution was mainly Poisson for dicentrics but gave a conflicting result for acentrics which was in excess.

Chromosome Aberrations

Enhanced frequency of chromosome aberrations in workers occupationally exposed to diagnostic X-rays.

To estimate the level of radiation exposure of personnel handling diagnostic X-ray machines, the yield of chromosomal aberrations was analysed in peripheral blood lymphocyte cultures. These occupationally exposed individuals showed higher frequencies of dicentrics as well as acentrics than normal controls. Absorbed radiation doses calculated by extrapolating reference in vitro dose-response curve for dicentrics ranged between 0.13 and 0.17 Gy. This implies exposure beyond the permissible limit of 0.05 Gy/year for the whole body. However, no obvious trend of increased aberrations as a function of either duration of employment or age was noticed. The increase in the aberration yields in this personnel underscores the need of adopting measures to avoid or minimise such overexposure.

Adult

Unruptured aneurysms of the intracavernous internal carotid artery: outcome following carotid ligation or conservative treatment.

Although intracranial obliteration or detachable balloon occlusion of the proximal artery has been recommended for treatment of unruptured aneurysms of the cavernous sinus, carotid artery ligation continues to be used by many neurosurgeons. This study compares the long term outcome after carotid ligation with that following conservative treatment. Nine of 13 patients treated by common carotid ligation improved, two were unchanged but two patients subsequently needed internal carotid ligation (mean FU 8.2 years). Ten patients were managed conservatively. Three improved, six were unchanged and one patient died following intracranial haemorrhage (mean FU 6.9 years). The authors conclude that carotid ligation remains an acceptable method for treating these difficult lesions.

Adult

Subdural empyema.

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Empyema, Subdural

Carotid ligation: what happens in the long term?

The authors reviewed a consecutive series of 115 patients who underwent common carotid ligation during the period 1954-1984. Average follow-up was 10 years. Seventy-three (63%) patients presented following a subarachnoid haemorrhage (SAH) and 42 (36%) presented with the mass effect of an unruptured aneurysm. Thirty-nine (34%) patients were lost to follow-up of whom 27 had had a previous SAH. Forty-six (63%) of the 73 patients traced had suffered a SAH and amongst this group, 11 patients (24%) died from a proven or suspected recurrent haemorrhage within 10 years of ligation. The fatal recurrent haemorrhage rate was, therefore, 2.4%/year. Thirty (71%) of the 42 patients who presented with unruptured aneurysms were traced. Seven of these (23%) died: two following haemorrhage, 1 year and 16 years after carotid ligation and three patients died as a direct consequence of carotid ligation. Check angiographic studies were available for 55 patients following carotid ligation, a mean of 8.4 years after the procedure. Thirteen were conventional angiograms and 42 were intravenous angiograms obtained using the digital subtraction technique. Seventy-six per cent of the aneurysms visualised on the initial studies were either smaller or had apparently disappeared. Only four new aneurysms were detected and in two of these instances, the initial angiographic studies had been incomplete. The authors conclude that the annual rate of fatal recurrent haemorrhage from an intracranial aneurysm following common carotid ligation is of a similar magnitude to that of the natural history of conservatively managed ruptured intracranial aneurysms. Moreover, carotid ligation apparently does not prevent haemorrhage from a previously unruptured aneurysm and the procedure appears to carry a significant morbidity and mortality, even in patients with an unruptured aneurysm.

Adult

Influence of milk, yoghurt and calcium on cholesterol-induced atherosclerosis in rabbits.

Five groups of rabbits were studied to determine the effect of milk, yoghurt and calcium on cholesterol-induced hypercholesterolaemia and atherosclerosis. The experiment lasted for only 16 weeks. Yoghurt, calcium and milk reduced serum cholesterol levels in rabbits fed on the cholesterol diet. There was no significant difference in the cholesterol levels in the yoghurt and calcium groups. Yoghurt caused a greater extent of hypocholesterolaemia than milk (P less than 0.001). Aortic sudanophilia was maximal in the cholesterol-fed group, while there was no sudanophilia in the yoghurt-fed group. The milk and calcium groups showed an intermediate degree of sudanophilia. Aortic sudanophilia correlated with the serum cholesterol level (r = +0.65). It is suggested that calcium is an active factor in yoghurt, but that other hypocholesterolaemic agents may also be present.

Animals