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Biomedical subjects

A N Jha

Publications and source records attributed to A N Jha.

At least 19 recordsLinked to original sources
PubMed2001

Fitness parameters and DNA effects are sensitive indicators of copper-induced toxicity in Daphnia magna.

This study compared the effects occurring at molecular and population levels in Daphnia magna exposed to copper concentrations in the range of 15-120 microg/l. The qualitative and quantitative modifications arising in random amplified polymorphic DNA (RAPD) profiles as a measure of DNA effects were compared with a number of key ecological fitness parameters, namely, the age-specific survival, age-specific fecundity, net reproductive rate, and intrinsic rate of population increase. Results suggested that growth, reproduction, and most of the fitness parameters as well as genomic template stability (a qualitative measure reflecting changes in RAPD profiles) were significantly affected at copper concentrations of 90 and 120 microg/l. Among the fitness parameters, the age-specific fecundity and net reproductive rate were the most sensitive parameters of toxicity. Changes in RAPD patterns generally occurred at copper concentrations of 90 and 120 microg/l, but with one primer, changes significantly arose at all copper concentrations. Overall, molecular and population parameters compared well and represented a sensitive means to measure toxicity induced by copper in Daphnia magna. In conclusion, the measurement of parameters at both molecular and population levels is valuable for investigating the specific effects of agents interacting with DNA. Ultimately, this methodology may allow the ecotoxicological examination of the link between molecular alterations and measurable adverse effects at higher levels of biological organization.

Animals↗
PubMed2000

Detection of genotoxins in the marine environment: adoption and evaluation of an integrated approach using the embryo-larval stages of the marine mussel, Mytilus edulis.

In genetic ecotoxicology or eco-genotoxicology, there is lack of well-validated systems which could demonstrate the utility of multiple endpoints in environmental quality assessment. For an evaluation of genotoxic potential of heterogeneous marine sediment samples collected from a small fishing harbour in the UK, an in vivo test system using embryo-larval stages of the common mussel, Mytilus edulis was validated against direct and indirect acting reference mutagens. The system appeared to be sensitive and reproducible for cytogenetic endpoints analysed (sister chromatid exchanges (SCEs) and chromosomal aberrations (CAbs)). Following validation and chemical characterisation of the environmental samples, multiple endpoints were measured. Determination of the maximum tolerated dose (MTD) was carried out as a measure to determine cytotoxic effects as a confounding factor for genotoxicity, based on developmental and cytotoxic (in terms of proliferative rate index or PRI) effects. Evaluation of the genotoxic potential of the samples gave a positive response for all the endpoints tested, linking different levels of biological organisation (i.e., chromosomal, cellular and organismal) for the observed effects. The study also emphasises the need for the assessment of the short and long-term impacts of dredge disposal on marine biota by including laboratory-based bioassays and incorporating an integrated approach which could yield as much useful information as possible in overall hazard and risk assessment for aquatic genotoxicity.

Animals↗
PubMed2000

Tributyltin induces cytogenetic damage in the early life stages of the marine mussel, Mytilus edulis.

Using an integrated approach, the genotoxic potential of bis(tri-n-butyltin), an antifouling agent known to disrupt endocrine system in marine invertebrates, has been evaluated in the embryo-larval stages of the edible mussel, Mytilus edulis. While evaluating the genotoxic potential, the toxicity of tributyltin was also taken into account by determining the maximum tolerated dose. The study suggested that tributyltin is capable of inducing cytogenetic damage (sister chromatid exchanges and chromosomal aberrations) in this target species. The study emphasises the need for further investigations of the potential genotoxic effects of this and other endocrine disrupters on ecologically relevant aquatic invertebrates, which contribute to the maintenance of ecosystems and that could potentially be harmful to human health via the food chain.

Animals↗
PubMed2000

Primary fibrosarcoma of brain.

This is a case presentation of a young patient with an intracranial space-occupying lesion following multiple episodes of generalised tonic clonic seizures for the last 20 years. Such a long latency period between the onset of fits and the discovery of an intracranial lesion is highly unusual in malignant brain tumours. This lesion was excised completely and proved to be a primary lesion of the brain - fibrosarcoma. These rare tumours of mesenchymal origin in the central nervous system are very rare.

Adult↗
PubMed1998

Assessment of developmental effects, cytotoxicity and genotoxicity in the marine polychaete (Platynereis dumerilii) exposed to disinfected municipal sewage effluent.

While sodium hypochlorite is widely used as a disinfectant for municipal sewage effluents and power station cooling waters discharged into coastal environments, there is limited information on the potential in vivo genotoxicity of such disinfection procedures to marine organisms. Using a recently developed test system based on the marine polychaete Platynereis dumerilii, we have evaluated impacts based on embryo-larval development, cytotoxicity and genotoxicity following exposure to disinfected settled (primary) effluent from a municipal sewage treatment works (STW). Sewage samples were collected from Newton Abbot STW, Devon, UK and then disinfected with sodium hypochlorite based on standard operational procedures. Exposure of polychaetes to dilutions of disinfected sewage in seawater (20 +/- 1 degree C) led to a marked reduction in normal embryo-larval development (7 h EC50 from 0.57-1.88% (v/v), n = 4), with a simultaneous increase in cytotoxicity. Following the calculation of the Maximum Tolerated Dose (MTD), based on developmental and cytotoxic effects, the organisms were also analysed for the induction of chromosomal aberrations. This investigation demonstrated the absence of genotoxicity in polychaetes exposed in vivo to sewage disinfected with sodium hypochlorite. These observations extend our previously published studies in which polychaetes exposed to non-disinfected sewage, while showing developmental toxicity and cytotoxicity, did not exhibit any evidence of cytogenetic damage.

Animals↗
PubMed1997

Evaluation of the genotoxicity of municipal sewage effluent using the marine worm Platynereis dumerilii (Polychaeta: Nereidae).

Samples of settled (primary) effluent were collected from a municipal sewage treatment works at Newton Abbot, Devon, UK, a site which discharges primary effluent via long sea pipeline into the English Channel (minimum of 200-fold initial dilution). Sewage samples were collected during the period February-April 1995 and were analysed for standard physico-chemical parameters (ammonia, chemical oxygen demand, conductivity, non-purgeable organic carbon and settled solids). Samples were also tested for cytotoxicity, genotoxicity, and for developmental effects in the embryo-larval stages of the marine worm, Platynereis dumerilii. Exposure to sewage concentrations of > or = 10% (v/v) in seawater at 20 +/- 1 degrees C led to a marked reduction in normal embryo-larval development (7 h EC50 values from 10% to 18% v/v, n = 5). There was also evidence of a simultaneous delay in the cell cycle progression (as determined by sister chromatid differential staining) following embryo-larval exposures to sewage concentrations of > or = 10% (v/v). Following the calculation of the Maximum Tolerated Dose (MTD), based on cytotoxic and developmental effects, cells from the same embryo-larvae were analysed for chromosomal aberrations (CAs). Results were consistent for all samples tested, demonstrating the absence of cytogenetic damage following the in vivo exposure of polychaete embryo-larvae to settled sewage.

Animals↗
PubMed1997

A simple technique to limit ICP catheter infection.

Infection of intracranial catheters is a common complication of ICP monitoring. The introduction of a simple technique of ensheathing the entire length of the external segment of the catheter in a sterile plastic sheath resulted in a decreased infection rate. In the study year, one of 78 patients developed catheter-induced meningitis, compared with seven of 64 patients in the year prior to the introduction of the protective plastic sheath. The use of a plastic sheath resulted in a low rate of infection.

Asepsis↗
PubMed1996

Development of an in vivo genotoxicity assay using the marine worm Platynereis dumerilii (Polychaeta: Nereidae).

An in vivo genotoxicity test system has been developed using the embryo-larval stages of the marine annelid, Platynereis dumerilii (Polychaeta: Nereidae). This species is representative of an ecologically important group of marine invertebrates, it is amenable to laboratory culture and has a well defined and stable karyotype (2n=28) which is suitable for the analysis of a range of cytogenetic endpoints, including chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). An evaluation of the cell cycle kinetics using the embryo-larval stages allowed selection of exposure times for cytogenetic work. Subsequently, 12-h-old embryos were exposed to reference mutagens, dissolved in sea water, in the presence of 5-bromodeoxyuridine (BrdU) for 12 h (SCE analysis) or 8 h (CA analysis) at 15 +/- 1 degree C, by which time they had reached the first larval stage (20-24h). Dose response-relationships for cytotoxicity, SCEs and CAs were observed for both direct acting mutagens (methyl methanesulfonate, mitomycin C) and mutagens which require metabolic activation (cyclophosphamide, benzo[a]pyrene). The sensitivity of the embryo-larval stages of P. dumerilii to both direct and indirect acting mutagens, their suitability for laboratory culture, together with the presence of a good karyotype and chromosome morphology for cytogenetic analyses, makes this species a potentially valuable in vivo model for marine genotoxicity testing.

Animals↗
PubMed1996

Simultaneous lumbar and intraventricular manometry to evaluate the role and safety of lumbar puncture in raised intracranial pressure following subarachnoid haemorrhage.

We report a prospective investigation of a bedside test to evaluate the role and safety of lumbar puncture in raised intracranial pressure in patients with subarachnoid haemorrhage. Fourteen patients who underwent aneurysm clipping following subarachnoid haemorrhage were studied. All patients had intraventricular drains and needed high volume cerebrospinal fluid (CSF) drainage to maintain the normal intracranial pressure. A lumbar puncture was performed in these patients and the simultaneous opening lumbar and ventricular pressures noted, CSF was then drained via the lumbar puncture, and the simultaneous closing lumbar and ventricular pressures noted. In all patients, the opening lumbar pressure was close to the ventricular pressure. In 13 of 14 patients, CSF drainage resulted in an equivalent and simultaneous fall of ventricular pressure. We concluded that simultaneous measurement of lumbar and ventricular CSF pressure before and after lumbar CSF drainage allows identification of candidates with differential cranial and lumbar pressures and therefore indicates safety or risk of lumbar CSF drainage.

Cerebral Ventricles↗
PubMed1995

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↗
PubMed1995

Localization of a vertebrate telomeric sequence in the chromosomes of two marine worms (phylum Annelida: class polychaeta).

Using the fluorescence in situ hybridization (FISH) technique, the presence of the vertebrate telomeric sequence (TTAGGG)n was found in the chromosomes of two marine polychaetes belonging to two separate orders: one errant, Platynereis dumerilii (family Nereidae), and the other sessile, Pomatoceros lamarckii (family Serpulidae). This sequence was exclusively present at the ends of the chromosomes in both species.

Animals↗
PubMed1995

Mimosine is a potent clastogen in primary and transformed hamster fibroblasts but not in primary or transformed human lymphocytes.

The cytogenetic effects of mimosine, a naturally occurring plant amino acid known to arrest cell-cycle progression at the G1-S border in cultured cells, have been studied. It was found that mimosine inhibits the cell-cycle progression in a dose-dependent manner in primary and transformed Chinese hamster fibroblasts as well as primary lymphocytes and transformed lymphoblastoid cells of human origin. In the Chinese hamster fibroblast cells, the first division metaphases analysed were found to be highly damaged or pulverized. The damaged cells which could pass through the next cell division, showed very high frequencies of sister chromatid exchanges (SCEs) compared with untreated second division cells. No such cytogenetic alterations could be detected in the human cells. The absence of clastogenic effect in cells of lymphoid origin appears to be related to the known capacity of these cells to undergo apoptosis, thereby efficiently eliminating cells with high frequencies of chromosomal aberrations. Our study demonstrates the clastogenic potency of mimosine and suggests the need for a careful interpretation of the results while using mimosine for cellular or molecular studies pertaining to cell cycle events.

Animals↗
PubMed1993

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↗
PubMed1993

Evaluation of intraoperative ultrasound in neurosurgery.

The value of real-time ultrasonography as a means of guidance during neurosurgical operations was assessed in a prospective study comprising 89 cases. There were 75 cranial and 14 spinal cases. After every such operation involving the ultrasonographic guidance, the operating surgeon subjectively assessed its usefulness vis-a-vis the information and/or help provided by it, on a scale ranging from 0 (no use) to 3 (invaluable). The intraoperative ultrasonographic guidance has been found to be extremely helpful in quickly and easily locating a small, deep-seated supratentorial lesion as also in certain spinal cases. In the absence of the much costlier CT/MRI-guidance system, intraoperative use of ultrasonography offers the desired help in majority of neurosurgical cases requiring intraoperative guidance. Additionally, it has got certain distinct advantages over the CT/MRI-guidance system.

Adolescent↗
PubMed1992

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↗
PubMed1992

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↗