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Biomedical subjects

S Basu

Publications and source records attributed to S Basu.

At least 253 records · Page 14Linked to original sources

Involvement of a 70-kb plasmid of the epidemic Shigella dysenteriae type 1 (Dt66) strain in drug-resistance, lipopolysaccharide synthesis, and virulence.

The present work characterizes a 70 kb plasmid of the Indian epidemic isolate Shigella dysenteriae type 1 strain Dt66 in relation to virulence and drug-resistance characters. Curing of the plasmids of Dt66 strain by acriflavine (AF) yielded seven groups of AF-cured derivatives. One group of derivatives containing 5 plasmids (70-2.5 kb) as against 6 (120-2.5 kb) in the wild type showed resistance to chloramphenicol, pivmecillinam, streptomycin, and tetracycline (CmrPivrSmrTcr) but sensitivity for ampicillin and nalidixic acid (AmsNals). This derivative when used as donor in conjugation experiments with a plasmidless E. coli KL318 strain (AmsCmsPivsSmrTcsNalr) as recipient, transferred only its 70 kb plasmid into the recipient with concomitant transfer of the CmrPivr phenotype. Both the donor and the transconjugant exhibited a diffuse pattern of adherence and produced keratoconjunctivitis in guinea pigs. Transconjugants contained a 42 kDa lipopolysaccharide band which was absent in recipient. Moreover, both donor and transconjugants showed Congo red binding ability. The results suggest that the 70 kb plasmid of S. dysenteriae Dt66 strain encodes not only Cmr,Pivr character but also is associated with virulence-related characters such as Congo red binding, LPS-biosynthesis, HeLa cell adherence, and keratoconjunctivitis related to virulence.

Animals↗

Predictors of the rate of renal function decline in non-insulin-dependent diabetes mellitus.

A multivariate analysis of 263 Mexican-American, African-American, and Non-Hispanic white non-insulin-dependent diabetes mellitus patients with end-stage renal disease revealed that in subjects following a linear course of decline of renal function, Mexican-American ethnicity (p = 0.0503) and female sex (p = 0.0036) hasten the rate of decline of renal function, while age (p = 0.0004), hypertension duration (p = 0.0058), and diabetes duration (p = 0.0587) slow the rate of decline of renal function. Blood pressure and glycemic control do not predict the rate of decline. These data suggest that ethnicity and sex-related factors may be as important as blood pressure and glycemic control during the course of non-insulin-dependent diabetic nephropathy.

Age Factors↗

Value of thallium-201 imaging in detecting adverse cardiac events after myocardial infarction and thrombolysis: a follow up of 100 consecutive patients.

OBJECTIVE: To determine the prognostic role of thallium-201 imaging compared with that of exercise electrocardiography in patients with acute myocardial infarction treated by thrombolysis. DESIGN: Patients who remained free of adverse cardiac events six weeks after myocardial infarction had stress and rest 201TI imaging and exercise electrocardiography and were followed up for 8-32 months. Adverse cardiac events (death, reinfarction, unstable angina, and congestive heart failure) were documented. SETTING: Large district general hospital, Middlesex. SUBJECTS: 100 consecutive male and female patients who were stable six weeks after thrombolysis for myocardial infarction. MAIN OUTCOME MEASURES: Prediction of occurrence of adverse cardiac events after myocardial infarction by exercise cardiography and 201TI myocardial perfusion imaging. RESULTS: Reversible ischaemia on 201TI imaging predicted adverse cardiac events in 33 out of 37 patients with such events during follow up (hazard ratio 8.1 (95% confidence interval 2.7 to 23.8), P < 0.001). Exercise electrocardiography showed reversible ischaemia in 33 patients, of whom 13 had subsequent events, and failed to predict events in 24 patients (hazard ratio 1.1 (0.56 to 2.2), P = 0.8). CONCLUSION: 201TI imaging is a sensitive predictor of subsequent adverse cardiac events in patients who have received thrombolysis after acute myocardial infarction, whereas exercise electrocardiography fails to predict outcome.

Adult↗

The Current State of Solar Modeling

Data from the Global Oscillation Network Group (GONG) project and other helioseismic experiments provide a test for models of stellar interiors and for the thermodynamic and radiative properties, on which the models depend, of matter under the extreme conditions found in the sun. Current models are in agreement with the helioseismic inferences, which suggests, for example, that the disagreement between the predicted and observed fluxes of neutrinos from the sun is not caused by errors in the models. However, the GONG data reveal subtle errors in the models, such as an excess in sound speed just beneath the convection zone. These discrepancies indicate effects that have so far not been correctly accounted for; for example, it is plausible that the sound-speed differences reflect weak mixing in stellar interiors, of potential importance to the overall evolution of stars and ultimately to estimates of the age of the galaxy based on stellar evolution calculations.

Journal Article↗

The Seismic Structure of the Sun

Global Oscillation Network Group data reveal that the internal structure of the sun can be well represented by a calibrated standard model. However, immediately beneath the convection zone and at the edge of the energy-generating core, the sound-speed variation is somewhat smoother in the sun than it is in the model. This could be a consequence of chemical inhomogeneity that is too severe in the model, perhaps owing to inaccurate modeling of gravitational settling or to neglected macroscopic motion that may be present in the sun. Accurate knowledge of the sun's structure enables inferences to be made about the physics that controls the sun; for example, through the opacity, the equation of state, or wave motion. Those inferences can then be used elsewhere in astrophysics.

Journal Article↗

Characterization of two glycolipid: alpha 2-3sialyltransferases, SAT-3 (CMP-NeuAc:nLcOse4Cer alpha 2-3sialyltransferase) and SAT-4 (CMP-NeuAc:GgOse4Cer alpha 2-3sialyltransferase), from human colon carcinoma (Colo 205) cell line.

Sialyltransferase activities, SAT-3 (CMP-NeuAc:nLcOse4Cer alpha 2-3sialyltransferase) and SAT-4 (CMP-NeuAc:GgOse4Cer alpha 2-3sialyltransferase), in Colo 205 cells catalyze the transfer of sialic acid to the terminal galactose of GlcNc-- and GalNAc-containing glycolipid substrates, respectively. Competition kinetic studies with nLcOse4Cer and GM1 as substrates in a sialyltransferase assay show that these two activities are catalyzed by two different catalytic entities. The two enzymes were co-solubilized with taurochlorate and resolved by DEAE--Cibacron Blue--Sepharose column chromatography into two elution peaks. The column eluent with SAT-3 activity failed to transfer sialic acid to asialo alpha(1)-acid glycoprotein, indicating that this enzyme is different from the sialyltransferase (ST3N) that synthesizes NeuAc alpha 2-3Gal linkage in asparagine-linked oligosaccharides of glycoprotein. However, SAT-3 activity can be immunoprecipitated with a polyclonal antibody produced against a protein expressed in Escherichia coli as GST-fusion protein from an ECB cDNA homolog of an alpha 2-3 sialyltransferase SAT-3 or STZ) the has been cloned from human melanoma cell and human placenta. Thus a concentration-dependent decrease in the residual SAT-3 activity relative to SAT-4 activity was observed in the supernatant after precipitation of the immune complex. Expression of SAT-3 (STZ) cDNA was also detected in Colo 205 cell by RT-PCR, followed by sequence analysis of the RT-PCR product. Characterization of the catalytic reaction products of SAT-3 and SAT-4 with thin-layer chromatography, sialidase treatment, and binding to specific antibodies indicates that both SAT-3 and SAT-4 catalyze the formation of alpha 2-3 linkage between sialic acid and terminal galactose of glycolipid substrates.

Base Sequence↗

Biosynthesis in vitro of neolactotetraosylceramide by a galactosyltransferase from mouse T-lymphoma: purification and kinetic studies; synthesis of neolacto and polylactosamine core.

The galactosyltransferase, GalT-4, which catalyses the biosynthesis in vitro of neolactotetraosylceramide, nLcOse4Cer (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc-Cer) from lactotriaosylceramide, LcOse3Cer (Glc NAc beta 1-3Gal beta 1-4Glc-Cer), and UDP-galactose has been purified 107 500-fold from a mineral oil induced mouse T-lyphoma P-1798, using affinity columns. The purified enzyme is partially stabilized in the presence of phospholipid liposomes. Two closely migrating protein bands of apparent molecular weights 56 kDa and 63 kDa were observed after sodium dodecyl sulfate polyacrylamide gel electrophoresis of highly purified mouse GalT-4. These two protein bands, when subjected to limited proteolysis, resulted in three peptides with identical mobilities indicating amino acid sequence identity between the proteins. Both protein bands from P-1798 gave a positive immunostain when tested with polyclonal antibody against bovine lactose synthetase (UDP-Gal:Glc beta 4-galactosyltransferase) following Western blot analysis on nitrocellulose paper. The enzyme has a pH optimum between 6.5 and 7.0 and like all other galactosyltransferases, GalT-4 has absolute requirements for divalent cation (Mn2+). The K(m) values for the substrate LcOse3Cer and donor UDP-galactose are 110 and 250 microM, respectively. Substrate competition studies with LcOse3Cer and either asialo-agalacto-alpha 1-acid glycoprotein or N-acetylglucosamine revealed that these reactions might be catalysed by the same protein. The only other glycolipid which showed acceptor activity toward the purified GalT-4 was iLcOse5Cer (GlcNAc beta 1-1-3Gal beta 1-4Lc3), the precursor for polylactosamine antigens. However, competition studies with these two active substrates using the most purified enzyme fraction, revealed that these two reactions might be catalysed by two different proteins since the experimental values were closer to the theoretical values calculated for two enzymes. Interestingly however, it seems that the GalT-4 from P-1798 has an absolute requirement for an N-acetylglucosamine residue in the substrate since the lyso-derivative (GlcNH2 beta 1-3Gal beta 1-4Glc-sphingosine) of the acceptor glycolipid LcOse3Cer is completely inactive as substrate while the K(m) and Vmax of the reacetylated substrate (GlcNAc beta 1-3Gal beta 1-4Glc-acetylsphingosine) was comparable with LcOse3Cer. Autoradiography of the radioactive product formed by purified P-1798 GalT-4 confirmed the presence of nLcOse4Cer, as the product cochromatographed with authentic glycolipid. The monoclonal antibody IB-2, specific for nLcOse4Cer, also produced a positive immunostained band on TLC as well as giving a positive ELISA when tested with radioactive product obtained using a highly purified enzyme from mouse P-1798 T-lymphoma.

Animals↗

Neuropeptide Y modulation of sympathetic activity in myocardial infarction.

OBJECTIVES: We examined the possible effect of neuropeptide Y in modulating central sympathetic activity after myocardial infarction in rats. BACKGROUND: Previous studies have shown the coexistence of neuropeptide Y and norepinephrine in the brain and a possible functional interaction between the two. Neuropeptide Y inhibits the release of norepinephrine at the presynaptic level and can be considered to act as a neuromodulator. METHODS: Two groups of rats were examined in this study-an experimental group, defined as those rats undergoing left coronary artery ligation, and a sham group without coronary artery ligation, serving as the control group. The animal in both groups underwent microdialysis in the paraventricular nucleus at 2, 4 and 8 weeks after operation. Microdialysis samples were collected with and without injecting neuropeptide Y in the paraventricular nucleus. The concentration of norepinephrine was determined by injecting purified microdialysate samples during high performance liquid chromatography. To explore the receptor's possible role, autoradiographic localization of neuropeptide Y receptors in the paraventricular nucleus was also carried out in the experimental and sham groups. RESULTS: The concentration of norepinephrine measured in the samples was decreased by 50% with neuropeptide Y in 2- and 4-week old rats after infarction, but by only 20% (p < 0.05) in 8-week old rats after infraction. The diminished inhibitory effects of neuropeptide Y on norepinephrine release was associated with increased sympathetic activity, as reflected by plasma norepinephrine; 8-week old rats after infarction had almost a 100% (p < 0.05) increase in their plasma norepinephrine level compared with the sham group. Autoradiography revealed a significant decrease in density of neuropeptide Y receptors in the paraventricular nucleus in 8-week old rats after infarction (p < 0.05). CONCLUSIONS: The data presented in this report suggest that the reduction of the inhibitory activation of neuropeptide Y on sympathetic release may contribute to elevated norepinephrine levels after myocardial infarction.

Animals↗

Development of a radioimmunoassay for latanoprost and its application in a long-term study in monkeys.

13,14-Dihydro-17-phenyl-18,19,20-trinor-PGF2 alpha-isopropyl ester (latanoprost) is a new prostaglandin drug developed for the treatment of glaucoma. In clinical trials a daily dose of 1.5 micrograms is effective in reducing the intraocular pressure. In toxicological studies doses from 2 micrograms/eye to 100 micrograms/eye have been used in various species. This paper reports the development and validation of a radioimmunoassay of latanoprost acid (PhXA85) and its application to toxicokinetic studies performed in monkeys. An antiserum was raised in rabbits by immunization with PhXA85 coupled to BSA at the carboxylic acid by the mixed anhydride method. The antibody titre was found to be about 1:2000 to 1:3000. The cross-reactivity with 13,14-dihydro-15(R,S)-17-phenyl-trinor-PGF2 alpha, 13,14-dihydro-15(S)-17-phenyl-trinor-PGF2 alpha, dinor-PhXA85. 17-phenyl-trinor-PGF2 alpha, latanoprost and PGF2 alpha was 46.4, 4.2, 7.6, 2.2, 0.1 and 0.039%, respectively. The intra-assay precision was between +/-7.7 and 11.7% (CV) at the level of 320 pg/ml and +/-8.3 and 9.7% with 1280 pg/ml in plasma samples from man, monkey, rat and aqueous humour from human and rabbit. Similarly, the intra-assay accuracy varied between 95.9 and 102.5% and 89.0 and 109.0% for the low and high standards, respectively. The inter-assay precision and accuracy were between +/- 6.0 and 13.4% and 91.0 and 92.8% in the monkey plasma samples. The limit of detection was 3 pg/tube or 30 pg/ml. In a long-term study, the acid of latanoprost was rapidly cleared from plasma in monkeys treated with eye drops of latanoprost (2 x 3 micrograms/day) over a period of 1 year.

Animals↗

Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation.

Ocular retardation (or) is a murine eye mutation causing microphthalmia, a thin hypocellular retina and optic nerve aplasia. Here we show that mice carrying the OrJ allele have a premature stop codon in the homeobox of the Chx10 gene, a gene expressed at high levels in uncommitted retinal progenitor cells and mature bipolar cells. No CHX10 protein was detectable in the retinal neuroepithelium of orJ homozygotes. The loss of CHX10 leads both to reduced proliferation of retinal progenitors and to a specific absence of differentiated bipolar cells. Other major retinal cell types were present and correctly positioned in the mutant retina, although rod outer segments were short and retinal lamination was incomplete. These results indicate that Chx10 is an essential component in the network of genes required for the development of the mammalian eye, with profound effects on retinal progenitor proliferation and bipolar cell specification or differentiation. off

Alleles↗

The association between cardiac events and myocardial ischaemia following thrombolysis in acute myocardial infarction and the impact of carvedilol.

The majority of post-myocardial infarction studies with beta-blocking drugs involved earlier generations. Newer drugs of this family with additional vasodilating and free-radical suppression properties, such as carvediol, are now available which may improve the prognosis still further. This double-blind, randomized, placebo-controlled, parallel group study was designed to assess the extent of myocardial ischaemia in clinically stable patients 6 weeks after acute myocardial infarction and thrombolysis, and to determine the influence of carvedilol on ischaemic events during the subsequent 6 months. One hundred and one patients who remained event free at 6 weeks post myocardial infarction underwent rest and exercise thallium-201 (TI-201) imaging. Reversible ischaemia was detected in 70 of the patients and there were 13 events in this group compared to one event in the 31 patients without ischaemia (P = 0.07). Four of the 56 patients on carvedilol and 10 of the 45 on placebo had adverse cardiac events (P = 0.04). In patients with reversible ischaemia carvedilol was more effective in reducing these events than was placebo (P = 0.03). These studies demonstrate that reversible myocardial ischaemia detected by TI-201 imaging is present in a large proportion of clinically stable patients following thrombolysis. In these patients, there is an increased cardiac event rate which is significantly reduced by carvedilol.

Adult↗

Diagnostic accuracy of dobutamine stress echocardiography for detection of coronary heart disease in hypertensive patients.

To compare the diagnostic accuracy between dobutamine echocardiography and treadmill exercise electrocardiography in detecting coronary artery disease in hypertensive patients, 43 patients without electrocardiographic evidence of left ventricular hypertrophy and basal ST-T changes, who had also undergone coronary angiography, were further evaluated by dobutamine echocardiography. The patients also underwent treadmill exercise echocardiography. Left ventricular mass index was calculated by echocardiography. Twenty-nine patients had coronary artery disease, of whom 22 had multi-vessel disease and 14 a normal coronary anatomy. Twenty-eight patients had an increased left ventricular mass index. The sensitivities of dobutamine echocardiography and exercise electrocardiography for detecting coronary artery disease were 93% and 72% (P = 0.08), respectively, and the specificities were 100% and 29% (P < 0.005), respectively. Logistic regression analysis showed exercise electrocardiography to be a poor predictor of coronary artery disease (P < 0.09) but dobutamine echocardiography was significantly better (P < 0.001). When patients with increased left ventricular mass index were excluded, prediction of coronary anatomy by exercise electrocardiography improved only marginally (p = 0.4) while dobutamine echocardiography was significantly better (P < 0.001). Thus dobutamine echocardiography is superior to exercise electrocardiography for diagnosis of coronary artery disease in hypertensive patients.

Aged↗