Blood supply of early hepatocellular carcinoma.
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Biomedical subjects
Publications and source records attributed to S Bhattacharya.
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By differential hybridization, we identified a number of genes in Saccharomyces cerevisiae that are activated by addition of cyclic AMP (cAMP) to cAMP-depleted cells. A majority, but not all, of these genes encode ribosomal proteins. While expression of these genes is also induced by addition of the appropriate nutrient to cells starved for a nitrogen source or for a sulfur source, the pathway for nutrient activation of ribosomal protein gene transcription is distinct from that of cAMP activation: (i) cAMP-mediated transcriptional activation was blocked by prior addition of an inhibitor of protein synthesis whereas nutrient-mediated activation was not, and (ii) cAMP-mediated induction of expression occurred through transcriptional activation whereas nutrient-mediated induction was predominantly a posttranscriptional response. Transcriptional activation of the ribosomal protein gene RPL16A by cAMP is mediated through a upstream activation sequence element consisting of a pair of RAP1 binding sites and sequences between them, suggesting that RAP1 participates in the cAMP activation process. Since RAP1 protein decays during starvation for cAMP, regulation of ribosomal protein genes under these conditions may directly relate to RAP1 protein availability. These results define additional critical targets of the cAMP-dependent protein kinase, suggest a mechanism to couple ribosome production to the metabolic activity of the cell, and emphasize that nutrient regulation is independent of the RAS/cAMP pathway.
Twenty-two X-linked cosmid clones have been localised by fluorescence in situ hybridisation (FISH). Twelve map to the long arm of the X chromosome and 10 to the short arm. Seven of the latter cosmids and an additional one were mapped by two colour FISH relative to reference markers DXS7 and DXS426 in proximal Xp. Finer localisation of one of the cosmids, namely HX43 was achieved by isolation of a microsatellite followed by genetic mapping with respect to reference markers in the region.
Complement-mediated pulmonary edema results from increases in lung capillary hydraulic conductivity (Lp), possibly by receptor-mediated mechanisms. We considered the Lp effects of vitronectin and the vitronectin-containing complement complex SC5b-9, which ligate the integrin alpha v beta 3. Vitronectin, SC5b-9, and SC5b-9-enriched zymosan-activated serum all rapidly increased Lp, as determined by the split-drop technique in single lung capillaries of rat lung. The Lp increases were inhibited by a monospecific (LM609) and a polyclonal (R838) antibody against the alpha v beta 3 integrin but not by an irrelevant monoclonal antibody isotype matched with LM609, by a monoclonal antibody against the alpha v beta 5 integrin, or by preimmune rabbit serum. Vitronectin monomers failed to increase Lp. The tyrosine kinase blockers genistein and methyl 2,5-dihydroxycinnamate caused significant concentration-dependent inhibitions of Lp increases due to vitronectin and zymosan-activated serum. By contrast, the protein kinase C blocker calphostin C had no major effect. We conclude that (1) multivalent ligation of the luminally located alpha v beta 3 integrin of lung capillary endothelium increases transcapillary liquid flux, and (2) the dominant signal transduction pathway for this effect occurs through tyrosine kinase activation.
The impact of Methyl parathion and Carbaryl was evaluated on an ecologically important soil Collembola, Cyphoderus sp. Enzyme characteristics demonstrate substrate optimum at 1 10(-2) mol/L temperature optimum at 30 degrees C with a pH requirement of 8.0. In vivo inhibition of whole body AChE reveals higher degree of inhibition by LD50 dose of Methyl parathion as compared to that of Carbaryl where maximum inhibition was noticed at the agricultural dose.
Seven cases of tuberculous cervicitis were detected out of 91 culturally and histologically established cases of uterine tuberculosis. There was simultaneous infection of cervix and endometrium in 4 cases and only cervical lesion in 3 cases. Two women gave a definite past history of primary extragenital tuberculosis-peritonitis in one and pulmonary lesion in the other. Clinically, cervix was predominantly hypertrophied in 4 cases and predominantly ulcerative in 3 cases. Acid-fast bacilli (Myco tuberculosis) were recovered from 5 cases, in abundance from 2 hypertrophied lesions and in sparse number from the 3 predominantly ulcerative lesions. Histological examination revealed pseudo-epitheliomatous hyperplasia with poor cellular response in the hypertrophied cervix and non-caseating tuberculous granuloma in predominantly ulcerative cervix. All the patients were from Darjeeling hills where endemic tuberculosis is high. An awareness of this entity is necessary while dealing with the cervical lesion of these patients.
Arterially administered iodized oil (Lipiodol) localizes selectively in HCCs for prolonged periods. Lipiodol-based intra-arterial chemotherapy and chemoembolization have yielded tumor response rates and survival benefits better than those offered by other therapies for unresectable Okuda Stage I and II HCC. Further trials are indicated to compare the different Lipiodol-cytotoxic-embolic regimens available. Early results of Lipiodol-targeted radiotherapy are available. This is a promising therapeutic development, and warrants comparison with chemoembolization in a large prospective randomized trial.
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The toxicity of cypenhymustine, a potential anticancer compound 1 (Cancer Letters, 70 (1993) 1-6), was assessed in normal as well as in Ehrlich ascites carcinoma (EAC), Sarcoma-180 (S-180) and Dalton's lymphoma (DL)-bearing Swiss male mice by measuring drug-induced changes in (1) hematological parameters and (2) femoral bone marrow cellularity on day 9 following drug treatment at the optimum dose of 3.0 mg/kg body weight from days 1 to 7. Detailed studies were also made by noting sequential changes in the above parameters in normal and EAC-bearing mice on days 12, 15, 18 and 21, respectively. The results indicate that the compound did not adversely affect hematopoiesis. From the sequential studies, it was observed that after a mild initial decrease in hematological counts, particularly in EAC-bearing treated mice, normalcy was reached within 11-14 days after termination of drug therapy. Drug induced hepatotoxicity and nephrotoxicity were also sequentially evaluated in normal and EAC-bearing mice on days 9, 12 and 15 but no such toxicities were detected. Also, body weight, skin and hair texture, and behavioural pattern (food and water intake and activity) did not reflect any toxic reaction in the host mice at this optimum dose.
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When injected into the hepatic artery the contrast agent Lipiodol (iodized poppy seed oil) is selectively retained by hepatocellular carcinoma (HCC) for a prolonged period of time. Liver computed tomography (CT) performed after Lipiodol angiography is more sensitive than ordinary CT at imaging HCC. Arterial administration of cytotoxic drugs and radioisotopes conjugated to Lipiodol has been shown to be reasonably safe in patients with irresectable HCC. These therapies, often combined with embolization, provide effective palliation, better tumour response and improved survival compared with other available treatments. Their use as a preoperative adjunct to surgical resection of HCC is controversial.
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The chief aim of this study was to maximize flap survival by counteracting the pathophysiological changes occurring during ischemia-reperfusion. Rabbit epigastric skin flaps given 21 hours of ischemia were infused intra-arterially with selected drugs at the start of reperfusion. Compared with control infused ischemic flaps, which had a 33% survival rate on day 7 post-ischemia, significant improvement was found with vasodilators nitrendipine (61%) and prostacyclin (65%) and the thrombolytic agent urokinase (65%); marginal improvement with the free radical scavenger desferrioxamine (53%); but no change with streptokinase (44%), heparin (21%), and ATP-MgCl2 (35%). A drug mixture comprising all of these agents except streptokinase and urokinase produced 87% survival, suggesting an additive effect. Biochemical assays on skin homogenates and blood implicated oxygen free radicals, neutrophil infiltration, and thromboxane in flap failure. These results imply that multiple factors are responsible for ischemic flap failure and that a mixture of drugs needs to be infused to counteract all of the detrimental changes.
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Histopathological changes in the head and trunk kidneys of Channa punctatus induced by chronic nonlethal levels of Elsan (211 ppb), mercuric chloride (16.7 ppb), and aqueous ammonia (15.64 ppm) were studied on 7, 28, 63, and 90 days of exposure. The pathology of the head kidney was characterized by degeneration and dispersion of interrenal and chromaffin tissue and necrosis in the haemopoietic elements. Kidney lesions were observed throughout the entire experimental period in fish exposed to Elsan and mercuric chloride. In contrast, the lesion induced by exposure to aqueous ammonia began to heal during the first phase of treatment. Marked abnormalities in trunk kidney histology were also found. Renal lesions consisted of minimal to mild multifocal, acute tubular epithelial degeneration, karyolysis, and dilation or shrinkage of Bowman's capsule and glomerulus. Elsan treatment resulted in a highly significant decrease in the dimension of Bowman's capsule and glomerulus at all days of sampling, except on Day 28. The response of the fish trunk kidney tissue to mercuric chloride was similar to that observed with Elsan exposure in terms of the alteration in the mean dimensions of Bowman's capsule and glomerulus. The response to ammonia was significant reduction in the size of Bowman's capsule and glomerulus throughout the experimental period except at Day 28. Little dilation of Bowman's capsule and a significant dilation of glomerulus were found at Day 28 of ammonia exposure. This study demonstrated that a chronic nonlethal exposure to Elsan, mercuric chloride affect both endocrine and excretory parts of the kidney while ammonia specifically damages the excretory part of the kidney of C. punctatus.