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Biomedical subjects

S Bhattacharya

Publications and source records attributed to S Bhattacharya.

At least 271 records · Page 15Linked to original sources
PubMed1996

Human liver cancer cells and endothelial cells incorporate iodised oil.

Iodised oil (lipiodol) administered via the hepatic artery localises selectively in primary liver cell cancers (hepatocellular carcinomas or HCCs) for prolonged periods and has been used as a vehicle for cytotoxic agents. Despite clinical use, the mechanism of lipiodol retention by tumours has remained unclear, embolisation of oil droplets in the tumour vasculature being the prevailing hypothesis. We have investigated the role of tumour and endothelial cells in lipiodol retention. Human liver tumour (Hep G2) cells and human umbilical vein endothelial cells in culture were exposed to lipiodol. Light microscopy using selective silver impregnation stains and transmission electron microscopy revealed lipiodol incorporation by both cell types, probably by pinocytosis. This was not associated with cellular injury in terms of cell lysis, cell replication or radio-labelled leucine uptake. Histological analysis of 24 HCCs either surgically resected or discovered incidentally at liver transplantation (with prior arterial injection of lipiodol) revealed vesicles of lipiodol in the cytoplasm of tumour cells and endothelial cells lining tumour vessels. Thus, lipiodol is likely to deliver cytotoxic agents directly into tumour cells and endothelial cells, both in vitro and in vivo. This may also apply to other lipids and to other human tumours. These findings have significant therapeutic implications.

Carcinoma, Hepatocellular↗
PubMed1996

A comparison of bladder and ovarian function two years following hysterectomy or endometrial ablation.

OBJECTIVE: To test the hypothesis that at two years bladder and ovarian function function are no different following either simple hysterectomy or endometrial ablation (transcervical resection/laser ablation). DESIGN: Randomised controlled trial comparing hysterectomy with endometrial ablation. Two years after trial entry bladder and ovarian function were evaluated subjectively by means of questionnaires and objectively by means of cystometry and estimation of serum follicle stimulating hormone respectively. SETTING: Aberdeen Royal Infirmary. PARTICIPANTS: Tow hundred and four women with dysfunctional uterine bleeding who, when recruited to the initial study two years previously, were aged less than 50 years, weighed less than 100 kg, and who would otherwise have undergone hysterectomy. RESULTS: Of the 204 women originally recruited, 101 re-attended the clinic and underwent cystometry and follicle stimulating hormone estimation. These, together with a further 59 women, completed postal questionnaires (79% of original cohort). Rates of stress incontinence (44% vs 44%, 95% CI of difference -16% to +15%), urge incontinence (21% vs 19% 95% CI of difference -11% to +14%), and hot flushes (30% vs 44%, 95% CI of difference -25% to +7%) were similar in the hysterectomy and endometrial ablation groups, respectively. Cystometry revealed 14 (31%) cases of bladder dysfunction after hysterectomy and 17 (35%) after hysteroscopic surgery (95% CI of difference -23% to +15%). Serum follicle stimulating hormone levels > 40 IU/L [corrected] were found in three (6%) women following hysterectomy and five (10%) of women after endometrial ablation. CONCLUSION: This study suggests that in comparison with endometrial ablation, simple hysterectomy for dysfunctional uterine bleeding does not compromise bladder or ovarian function, at least at two years after the operation. Due to lack of power the estimates of any differences are imprecise, and clinically significant effects cannot be ruled out.

Adult↗
PubMed1996

Replication initiates at multiple dispersed sites in the ribosomal DNA plasmid of the protozoan parasite Entamoeba histolytica.

In the protozoan parasite Entamoeba histolytica (which causes amoebiasis in humans), the rRNA genes (rDNA) in the nucleus are carried on an extrachromosomal circular plasmid. For strain HM-1:IMSS, the size of the rDNA plasmid is 24.5 kb, and 200 copies per genome are present. Each circle contains two rRNA transcription units as inverted repeats separated by upstream and downstream spacers. We have studied the replication of this molecule by neutral/neutral two-dimensional gel electrophoresis and by electron microscopy. All restriction fragments analyzed by two-dimensional gel electrophoresis gave signals corresponding to simple Y's and bubbles. This showed that replication initiated in this plasmid at multiple, dispersed locations spread throughout the plasmid. On the basis of the intensity of the bubble arcs, initiations from the rRNA transcription units seemed to occur more frequently than those from intergenic spacers. Multiple, dispersed initiation sites were also seen in the rDNA plasmid of strain HK-9 when it was analyzed by two-dimensional gel electrophoresis. Electron microscopic visualization of replicating plasmid molecules in strain HM-1:IMISS showed multiple replication bubbles in the same molecule. The location of bubbles on the rDNA circle was mapped by digesting with PvuI or BsaHI, which linearize the molecule, and with SacII, which cuts the circle twice. The distance of the bubbles from one end of the molecule was measured by electron microscopy. The data corroborated those from two-dimensional gels and showed that replication bubbles were distributed throughout the molecule and that they appeared more frequently in rRNA transcription units. The same interpretation was drawn from electron microscopic analysis of the HK-9 plasmid. Direct demonstration of more than one bubble in the same molecule is clear evidence that replication of this plasmid initiates at multiple sites. Potential replication origins are distributed throughout the plasmid. Such a mechanism is not known to operate in any naturally occurring prokaryotic or eukaryotic plasmid.

Amebiasis↗
PubMed1996

Thyroid hormone induces the generation of a novel putative protein in piscine ovarian follicle that stimulates the conversion of pregnenolone to progesterone.

Ovarian follicles were collected from the perch belonging to the vitellogenic stage and incubated in vitro for 4 h in the absence (control) or presence of triiodothyronine (T3). Addition of T3 (40 ng/ml) to the follicle incubation caused a two-fold increase of [3H] pregnenolone conversion to radiolabelled progesterone (P4) as compared to the control. The increase in P4 formation in the ovarian follicle could be blocked completely by the inhibitors of protein synthesis, actinomycin D and cycloheximide (50 micrograms/ml), suggesting a protein or peptide mediator of the T3 stimulatory effect. To search for this mediator, ovarian follicles from the control or T3 incubate were homogenized and ultracentrifuged and different fractions were added separately to fresh follicle incubations. Only the 100,000 g supernatant from T3 incubate showed a significant (p < 0.01) increase in P4 formation, while the corresponding supernatant from control follicle incubations had no such stimulatory effect. Trypsin or heat destroyed this augmentory effect. Based on its ability to stimulate the conversion of radiolabelled pregnenolone to P4 in the ovarian follicle, the T3-induced protein (TIP) was purified to homogeneity by employing Sephadex G-75 gel filtration, FPLC Mono-Q and FPLC Superose-6 chromatography. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of purified TIP showed it to be a 52 K monomer protein. Addition of TIP in increasing concentrations to follicle incubations caused a linear increase in P4 formation. Experiments with radiolabelled TIP ([125I] TIP) indicate its entry through the follicular cell membrane within the limited period of incubation. Results suggest that TIP activates ovarian 3 beta-hydroxysteroid dehydrogenase enzyme, thus effecting a greater conversion of pregnenolone to P4.

Animals↗
PubMed1996

Thyroid hormone induces the synthesis of a putative protein in the rat granulosa cell which stimulates progesterone release.

125I-3,5,3'-tri-iodothyronine (T3) binds specifically to a pure nuclear preparation from rat granulosa cells. A Scatchard analysis of T3 binding showed a Kd of 0.65 x 10(-9) mol/l and a Bmax of 1.57 pmol/mg DNA. The biological relevance of T3 binding to granulosa cells was evaluated by adding T3 (20 ng/incubation) to granulosa cells (1 x 10(6) cells/incubation) which greatly stimulated progesterone release. T3-stimulated progesterone release was significantly inhibited by actinomycin-D (P < 0.01) and cycloheximide (P < 0.01). T3 caused about a twofold increase in granulosa cell protein synthesis as compared with the control which was inhibited by actinomycin-D and cycloheximide. The addition of T3 to granulosa cell incubations also resulted in a more than 2.5-fold increase in mRNA. The results indicated that T3 stimulation of progesterone release is mediated via T3-induced protein(s) or TIP. TIP was located in the soluble supernatant fraction (100,000 g supernatant; 100 k sup) from T3-incubated cells but could not be detected in the 100 k sup from the control cells or LH-incubated cells. TIP was purified based on its biological activity, i.e. its addition to granulosa cell incubations stimulated progesterone release into the medium. The 100 k sup from T3-incubated granulosa cells was subjected to Sephadex G-75 gel filtration, FPLC Mono Q and FPLC Superose 6 chromatography which resulted a 273-fold purification over the starting material and a clearly homogeneous protein was obtained. SDS-PAGE of purified TIP showed it to be a 53 kDa monomer protein. Experiments conducted with radiolabelled TIP suggested internalization of TIP into the granulosa cell. The results therefore showed that T3 induces the synthesis of mRNA and proteins in rat granulosa cells and that one of the proteins is TIP which, in turn, stimulates progesterone release from the cell, suggesting thereby that this putative protein is a novel mediator of T3 function in the granulosa cell.

Animals↗
PubMed1996

Effects of long-term treatment with the allosteric enhancer, PD81,723, on Chinese hamster ovary cells expressing recombinant human A1 adenosine receptors.

In this study, desensitization and down-regulation of A1 adenosine receptors (A1AR) by the allosteric enhancer PD81,723 (PD) and by N6-cyclopentyladenosine (CPA) were investigated after 24-hr pretreatment of CHO-K1 cells stably expressing recombinant human A1AR. Pretreatment with 20 microM PD and 10 microM CPA caused a 1.5- and 4.0-fold, respectively, desensitization (reduced potency of CPA to lower cAMP). Pretreatment with PD and/or CPA did not modify the acute effect of PD to increase (5-fold) the potency of CPA. Radioligand binding was used to measure receptor down-regulation in cell membranes and in intact cells. Pretreatment of cells with PD had no effect on the number of membrane binding sites for the agonist [125I] N6-(3-iodo-4-aminobenzyl) adenosine or for the antagonist, [3H]8-cyclopentyl-1,3-dipropylxanthine, but the binding of these radioligands to intact cells was modestly reduced (20-37%), possibly reflecting an effect of pretreatment on receptor subcellular distribution. Pretreatment of cells with CPA produced large ( > 40%) reductions in the binding of radioligands to both membranes and intact cells. Pretreatment of cells with CPA also increased the number of presumed internalized receptors measured as [3H]8-cyclopentyl-1,3-dipropylxanthine binding sites in intact cells insensitive to blockade by the charged antagonist 8-sulfophenyltheophylline. The relatively small degree of functional desensitization and down-regulation of A1AR caused by long term exposure of cells to PD is considered to be encouraging in terms of the therapeutic potential of the allosteric enhancer class of compounds.

Adenosine↗
PubMed1996

Involvement of mercury in platelet aggregation--probable mechanism of action.

Both in vivo and in vitro Hg2+ caused dose dependent inhibition of rat platelet aggregation. However, as low a dose as 88.8 pM Hg2+ could initiate ADP-induced aggregation even in the absence of added calcium. The action of Hg2+ was found to be unaffected by antagonists such as cAMP and theophylline either alone or in combination. Hg2+ induced platelet aggregation was inhibited completely by pre-incubation with aspirin (1 mmol.L-1), but it was ineffective when added after Hg2+. The results also indicate that the normal platelet function is affected by both high and low concentrations of Hg2+.

Adenosine Diphosphate↗
PubMed1996

Comparative evaluation of somatic & excretory-secretory antigens of Entamoeba histolytica in serodiagnosis of human amoebiasis by ELISA.

The excretory-secretory antigens collected from the axenic culture medium and conventional somatic antigen prepared from the whole trophozoites of E. histolytica were compared for their efficacy in serodiagnosis of amoebiasis. A total of 280 sera collected from different clinically proven cases of amoebiasis and healthy subjects were analysed against both the antigens in ELISA. Both antigens showed a 100 per cent correlation in amoebic liver abscess cases, patients infected with enteropathogens other than amoeba and healthy subjects. However, excretory-secretory antigens showed slightly higher detection rate in patients suffering from acute amoebic dysentery and asymptomatic cyst passers groups. These results clearly suggested the use of excretory-secretory antigens by ELISA for serodiagnosis of amoebiasis due to its better or equal sensitivity, specificity and easier preparation compare to conventional antigen. The use of excretory-secretory antigen in serodiagnosis will not only help in performing more tests utilizing the same chemicals, but also save the cost, time and troubles for importing the foreign chemicals required for cultivation of E. histolytica.

Animals↗
PubMed1996

The genesis, status and future of environmental toxicology.

This century has experienced the pinnacle of industrial, agricultural and electronic revolution; at the same time the so called progress is tainted with ecological disbalance and unprecedented environmental deterioration. Human induced calamities could only be tackled by human ingenuity and the eventual phenomenon was the advent of 'Environmental Toxicology'.

Animals↗
PubMed1996

Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11) and association with a unique bimodal expressivity phenotype.

Retinitis pigmentosa (RP) is the name given to a heterogeneous group of retinal degenerations mapping to at least 16 loci. The autosomal dominant form (ARP), accounting for approximately 25% of cases, can be caused by mutations in two genes, rhodopsin and peripherin/RDS, and by at least six other loci identified by linkage analysis. The RP11 locus for adRP has previously been mapped to chromosome 19q13.4 in a large English family. This linkage has been independently confirmed in a Japanese family, and we now report three additional unrelated linked U.K. families, suggesting that this is a major locus for RP. Linkage analysis in the U.K. families refines the RP11 interval to 5 cM between markers D19S180 and AFMc001yb1. All linked families exhibit incomplete penetrance; some obligate gene carriers remain asymptomatic throughout their lives, whereas symptomatic individuals experience night blindness and visual field loss in their teens and are generally registered as blind by their 30s. This "bimodal expressivity" contrasts with the variable-expressivity RP mapping to chromosome 7p (RP9) in another family, which has implications for diagnosis and counseling of RP11 families. These results may also imply that a proportion of sporadic RP, previously assumed to be recessive, might result from mutations at this locus.

Chromosome Mapping↗
PubMed1996

Evaluation of phthalmustine, a new anticancer compound. II. Tumor inhibitory effect in murine Ehrlich ascites carcinoma and sarcoma-180.

The antitumor activity of phthalmustine (Neoplasma, 41, 1994, 35) has been evaluated in murine Ehrlich ascites carcinoma (EAC) and sarcoma-180 (S-180). The hematological changes associated with the application of phthalmustine were also evaluated in tumor bearing as well as in normal male Swiss mice. The results indicate that phthalmustine induces marked inhibition of tumor growth and substantially prolongs host survival having curative effect while it does not adversely affect hematopoiesis at the optimum dose tested. No toxic symptoms were noted with respect to external appearance, body weight changes and behavioral pattern.

Animals↗