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Biomedical subjects

S Dogra

Publications and source records attributed to S Dogra.

At least 19 recordsLinked to original sources
PubMed1999

Asymmetric distribution of phosphatidylethanolamine in C. albicans: possible mediation by CDR1, a multidrug transporter belonging to ATP binding cassette (ABC) superfamily.

By using two molecular probes, we demonstrate that only 4% of total phosphatidylethanolamine (PtdEtn) in the plasma membrane (PM) of a human pathogenic yeast, Candida albicans, is present in its external half. Evidence is presented to show that the availability of PtdEtn could be related to the expression of a multidrug transporter CDR1 of C. albicans, and the process is energy-dependent. A homozygous CDR1 disruptant strain of C. albicans shows almost 23% reduction in the external labelling of PtdEtn. This report shows that, similar to human MDRs, yeast multidrug transporter could also be involved in aminophospholipid translocation.

ATP-Binding Cassette Transporters↗
PubMed1997

Tuberculous osteomyelitis.

Tuberculous osteomyelitis which does not involve a joint is uncommon and may fail to be diagnosed by an orthopaedic surgeon. We treated 28 lesions of tuberculous osteomyelitis in 25 patients between 1988 and 1995. The duration of symptoms was from two to 39 months, and most of our patients had been treated initially with non-steroidal anti-inflammatory drugs which failed to provide relief. Bone pain which does not promptly respond to analgesic medication is often due to infection or neoplasia. In the early stages, when plain radiographs are normal, MRI or CT may help to localise lesions. On plain radiographs, more advanced lesions may mimic chronic pyogenic osteomyelitis, Brodie's abscess, tumours or granulomatous lesions. Biopsy is mandatory to confirm the diagnosis, and antituberculous drugs are the mainstay of treatment. When operative findings at biopsy have the features of skeletal tuberculosis curettage of the affected bone may promote earlier healing.

Adolescent↗
PubMed1996

Pulmonary clearance of Candida albicans: effect of exposure to native and metal-coated fly ash.

The viability of Candida albicans was tested at various intervals in the lungs of rats following single intratracheal inoculation of the yeast cells. Most of the inoculated cells were cleared from lungs within 48 hr after exposure. Clearance was enhanced in lungs exposed to metal-coated fly ash than in those exposed to native fly ash. The validity of these studies was verified in vitro using peritoneal macrophages of mice exposed in vivo to native and metal-coated fly ash. An increase in phagocytic and intracellular killing of macrophages harvested from animals exposed to native or metal-coated fly ash was observed.

Animals↗
PubMed1995

Alterations in the pulmonary and systemic immune response in rats exposed to coal fly ash.

The effect of intratracheally injected fly ash on the development of pulmonary and systemic immunity was studied in rats. Following intratracheal and intraperitoneal immunisation with sheep red blood cells (SRBC) there was an appearance of antibody forming cells (AFC) in lung associated lymph nodes (LALN) of animals exposed to either fly ash or physiological saline. Enumeration of AFC in LALN after immunisation by either of the routes, revealed a reduction in the number of AFC in LALN of fly ash exposed rats in comparison to saline exposed animals. The reduction in the number of AFC was more pronounced after exposure of Cd-coated fly ash. The AFC appeared in the spleen only after immunisation through intraperitoneal route and the number of AFC in spleen of the fly ash and saline exposed group of animals did not show any significant difference. These results demonstrate that fly ash burden of lungs results in an impairment of the local immune response of the lungs without an associated effect on the systemic immunity.

Air Pollutants↗
PubMed1995

Effect of long and short fibre amosite asbestos on in vitro TNF production by rat alveolar macrophages: the modifying effect of lipopolysaccharide.

The influence of long and short fibre amosite on the generation of tumor necrosis factor (TNF) by rat alveolar macrophages was investigated in vitro. TNF rich supernatants were prepared from macrophages cultured in F10 medium +2% Bovine Serum Albumin (BSA). Spontaneously released TNF from unstimulated macrophages and TNF rich supernatants from macrophages exposed to Lipopolysaccharide (LPS) and fibres were stored at -70 degrees C and then tested for their cytotoxicity towards L929 cells. Maximum spontaneously released TNF was obtained from 24 hour macrophage cultures. Short amosite fibres had no significant effect in stimulating alveolar macrophages to release TNF while the 50 micrograms dose of long fibres resulted in significantly increased release of TNF. Cotreatment of alveolar macrophages with LPS and fibres further enhanced the TNF production and maximum production was obtained with LPS +50 micrograms dose of long fibre resulted in significantly increased release of TNF. Co-treatment of alveolar macrophages with LPS and fibres further enhanced the TNF production and maximum production was obtained with LPS +50 micrograms of long fibre amosite. The present study indicates that fibre dimension is a major factor in in vitro dust activity and TNF has a possible active role to play in dust induced inflammation in vivo.

Animals↗
PubMed1995

Pattern of injuries in a hydro-electric project.

A study of work-related injuries at a hydro-electric project site (May 1991-April 1992) was undertaken to determine the incidence and pattern of the injuries out of a total number of 119 injuries in the year. A significant proportion of these were orthopaedic in nature and the commonest site of injury was limbs (both upper and lower limbs) like auto-amputations and head injuries. A large proportion of these accidents (24.37%) resulted in permanent disability likely to interfere in the normal activities or locomotion of those injured.

Accidents, Occupational↗
PubMed1994

Stable heterologous expression of hydroxysteroid sulphotransferase in Chinese hamster V79 cells and their use for toxicological investigations.

Various benzylic alcohols are metabolically activated to electrophilic, potentially mutagenic and carcinogenic sulphuric acid esters. The involved sulphotransferases are not expressed in the cell lines in culture which are commonly used for mutagenicity testing. The liver of adult female rats is very efficient in the bioactivation of 1-hydroxymethylpyrene. The major enzyme involved was purified and identified as hydroxysteroid sulphotransferase a. Its cDNA was stably expressed in Chinese hamster V79 cells, which are particularly suited for the quantitative detection of various types of mutations and other genotoxic and cytotoxic effects. The mRNA, protein and enzyme activity levels in the constructed cell lines (V79rSTa-1 and V79rSTa-2) were measured, and the cells were also used in mutagenicity and cytotoxicity investigations with benzylic alcohols. 1-Hydroxymethylpyrene, 9-hydroxymethylanthracene and 6-hydroxymethylbenzo[a]pyrene showed enhanced cytotoxicity in V79rSTa-1 and V79rSTa-2 cells, as compared with sulphotransferase-deficient control cells. In addition, 1-hydroxymethylpyrene induced sister chromatid exchanges, and 6-hydroxymethylbenzo[a]pyrene induced gene mutations in V79rSTa-1 cells. We intend carrying out more investigations with other chemicals on these cell lines. Their advantages, as compared with systems with external metabolising systems, include the formation of the active metabolites within the target cell, as in ST-proficient cells in vivo, eliminating the problems which may result from restricted intercellular transport of reactive and ionized sulphuric acid conjugates. Furthermore, cells expressing other sulphotransferases, including human enzymes, may be constructed and used for comparative investigations.

Animals↗
PubMed1992

Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization.

Fibre length has been shown to be an important factor in the ability of respirable fibres to cause lung fibrosis and cancer. We have reported that a long sample of amosite asbestos is more carcinogenic and fibrogenic than a short sample of similar diameter. These amosite asbestos samples were studied with regard to their ability to stimulate the release of the pro-inflammatory cytokine tumour necrosis factor (TNF) from rat alveolar macrophages in vitro. The long fibre sample was found to stimulate substantially greater release of the cytokine than the short sample. Furthermore, on treatment of the fibres with rat immunoglobulin G (IgG), there was an increase in the ability of both the long and the short sample to stimulate TNF secretion, although the long sample retained by far the greatest activity. Coating of the fibres with a range of other proteins had no substantial effect on their ability to stimulate TNF secretion. Quartz and titanium dioxide (TiO2) were included as control particles and the TNF-stimulating activity of quartz was notably increased by opsonization with IgG. TiO2 showed a similar low activity to that of the short fibre sample of amosite but this again could be modestly increased by opsonization with IgG. The simulation of TNF release caused by treatment with immunoglobulin-opsonized long fibre amosite could be inhibited by treatment of the macrophages with the protein kinase C-inhibitor staurosporine. The study demonstrates a fibre length-related ability to stimulate cytokine secretion by alveolar macrophages, and its enhancement by opsonization with IgG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Stable expression of rat cytochrome P450IA2 cDNA and hydroxylation of 17 beta-estradiol and 2-aminofluorene in V79 Chinese hamster cells.

In continuation of our work toward the establishment of a working cell bank for metabolic and toxicological studies, V79 Chinese hamster cells were genetically engineered for stable expression of rat cytochrome P450IA2. Full-length cDNA encoding rat P450IA2 was obtained by searching a cDNA library made from Aroclor 1254-induced rat liver mRNA and by joining a small 5'-end fragment to a fragment containing the rest of the cDNA. The sequence of the cDNA was confirmed by DNA sequencing and comparison to a previously published cDNA sequence. The reconstructed full-length cDNA was inserted into a simian virus 40 early promoter-containing eukaryotic expression vector and cotransferred with the neomycin phosphotransferase gene as a selective marker into V79 cells by the calcium/phosphate-coprecipitation technique. G418-resistant V79 cell clones were checked for chromosomal integration of the cDNA by Southern blotting, for expression of authentic mRNA and protein by northern and western blotting, and for P450IA2-specific enzymatic activities such as hydroxylation of 17 beta-estradiol and 2-aminofluorene.

Amino Acid Sequence↗
PubMed1991

The use of genetically engineered V79 Chinese hamster cultures expressing rat liver CYP1A1, 1A2 and 2B1 cDNAs in micronucleus assays.

We have undertaken a comparative study of the bioactivation of a panel of promutagens by V79 Chinese hamster cells genetically engineered to metabolic competence. In vitro micronucleus assays of the test agents in V79 cultures in the presence of an Aroclor induced rat S9 yielded positive results. In the genetically engineered cell lines, benzo[a]pyrene was metabolized specifically by the 3-methylcholanthrene inducible rat liver CYP1A1 (cell line XEM2) whereas cyclophosphamide increased the micronucleus frequency only in cultures expressing the phenobarbital inducible CYP2B1 (SD1). Following exposure to the mycotoxin sterigmatocystin, elevated frequencies of micronucleated cells were recorded in XEM2, SD1 and XEMd-MZ (expresses the isosafrole inducible CYP1A2) cells. The aromatic amine 2-amino-anthracene elicited a weak response in the cell line XEMd-MZ which expressed CYP1A2. This response was enhanced when this cDNA was expressed in a V79 variant cell strain which also possessed endogenous acetyltransferase activity. Upon exposure to tobacco particulate matter, a greater induction of micronuclei was observed in the XEM2 cell line compared to V79 cultures, implicating polycyclic aromatic hydrocarbons in addition to direct-acting compounds as causal agents in the genotoxicity of tobacco particulate matter. The cytokinesis blocked in vitro micronucleus assay provides a faster, simpler alternative to metaphase analysis, and kinetochore labelling techniques enable the discernment of both structural and numerical chromosome changes. The inclusion of metabolically competent test strains in the in vitro micronucleus assay therefore creates a powerful system for detecting genotoxins and may be extended to elucidate both mechanisms of bioactivation and modes of genotoxic insult.

Animals↗
PubMed1990

Successful difficult intubation. Tracheal tube placement over a gum-elastic bougie.

A randomised study was carried out to assess the effect of tracheal tube rotation on the passage of a tube over a gum-elastic bougie into the trachea in 100 patients. The effect of the presence or absence of a laryngoscope on successful tube placement was also assessed. A grade 3 difficult intubation was simulated in patients with a laryngoscope. There was a significant difference in the rates for successful first-time intubation in those patients with tube orientation of -90 degrees (with the bevel facing posteriorly) as compared with a tube orientation of 0 degrees (the normal orientation with the bevel facing left). The unsuccessful first-time intubations with a 0 degree orientation were frequently converted to successful intubations with the -90 degrees position at a second attempt. The presence of a laryngoscope in the mouth while rail-roading a tube over the bougie also made a significant difference to the rate of successful first-time intubations. The most successful method was to leave the laryngoscope in the mouth and rotate the tube to -90 degrees.

Adolescent↗
PubMed1990

Stable expression of rat cytochrome P-450IA1 cDNA in V79 Chinese hamster cells and their use in mutagenicity testing.

V79 Chinese hamster cells genetically engineered to express cytochrome P-450IA1 are reported. A full length cDNA encoding rat cytochrome P-450IA1 was obtained from a cDNA library prepared from rat liver mRNA. The cDNA was recombined with the SV40 early promoter and expressed in V79 cells. Three V79-derived P-450IA1-expressing cell lines (XEM1, XEM2, and XEM3) were established. The presence of the rat cytochrome P-450IA1 cDNA in these hamster cells was confirmed by Southern blotting. The transcription of the cDNA into mRNA and translation into the desired cytochrome P-450 protein was detected by Northern and Western blotting. The enzymatic activity was determined by the cytochrome P-450IA1-dependent oxidation of benzo[a]pyrene and 7-ethoxycoumarin. After exposure to benzo[a]pyrene, the mutant frequency increased in XEM1 and XEM2 cells and was higher than in V79 cells in the presence of an exogenous activating system. The mutant frequency was even more increased when XEM1 and XEM2 cells were exposed to the proximate mutagen (trans)-7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene.

Animals↗
PubMed1990

Alterations in in vitro functional activities of alveolar macrophages exposed in vivo to mineral dusts.

To determine whether macrophages exposed to mineral dusts are altered, rats were exposed intratracheally to one of several mineral dusts, held 8 days, their lungs washed and the cellular composition of the fluid characterized morphologically and functionally. The number of cells recovered from lung washings of exposed rats increased 2 to 5 times relative to control rats; however, the percentage of such cells that were macrophages, or were capable of phagocytosis, adherence to glass or metabolism of carbohydrates via the hexose monophosphate shunt as indicated by reduction of nitroblue tetrazolium, were reduced. Silica dust produced the greatest effect, corresponding qualitatively to earlier in vivo studies.

Aluminum Oxide↗
PubMed1989

Genetically engineered V79 Chinese hamster cell expression of purified cytochrome P-450IIB1 monooxygenase activity.

Chinese hamster V79 fibroblasts, frequently used as target cells in short-term tests for mutagenicity, do not possess measurable monooxygenase activity; in particular, enzymatic oxidation of testosterone (T) cannot be demonstrated. If these V79 cells, however, had been transfected with the cDNA-encoding rat liver cytochrome P-450IIB1 under control of the SV40 early promoter, they stably expressed monooxygenase activity. These so-called SD1 cells then oxidatively metabolized T at a rate of 27 pmol/mg protein/min, converting it to 16 alpha- and 16 beta-hydroxy-T as well as 4-androsten-3,17-dione as sole metabolites in a ratio of 1.1:1.0:1.6. The regio- and stereoselective conversion of T by SD1 cells, as well as the quantitative distribution of the metabolites, corresponds well with the results reported for pure cytochrome P-450IIB1 in a reconstituted system.

Animals↗