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Biomedical subjects

A Sinha

Publications and source records attributed to A Sinha.

At least 73 records · Page 4Linked to original sources
PubMed2000

Total synthesis of asimicin and bullatacin.

The efficient total synthesis of asimicin, 1, and bullatacin, 2, has demonstrated the advantages of three different strategies for the synthesis of the tricyclic intermediates 6 and 7, which represent the key fragment of the bis-THF Annonaceous acetogenins. The naked carbon skeleton strategy is based on the production of all asymmetric centers by selective placement of the oxygen functions onto an unsaturated, nonfunctionalized carbon skeleton. Diversity in this approach arises from the relative timing of highly stereoselective reactions, such as the Sharpless asymmetric dihydroxylation (AD) reaction, the Kennedy oxidative cyclization (OC) with rhenium(VII) oxide, the Mitsunobu-type alcohol epimerization reaction, and the Williamson etherification reaction. The convergent strategy, which is based on the combinatorial coupling of two series of diastereomeric fragments, to produce intermediates such as 11 and 12, enjoys the advantages of both efficiency and versatility. The third approach, which is based on partially functionalized intermediates, such as 13, combines the advantages of both the linear and the convergent strategies-synthetic efficiency and diversity.

Antineoplastic Agents, Phytogenic↗
PubMed2000

A possible origin of differences between calorimetric and equilibrium estimates of stability parameters of proteins.

To test the validity of thermodynamic parameters from the equilibrium method, we have studied the reversible heat-induced denaturations of lysozyme, ribonuclease A, cytochrome c and myoglobin at various pH values, using absorption spectral measurements. For each protein, if a linear temperature-dependence of the pre- and post-transition baselines is assumed for the analysis of the conformational-transition curve, the estimate of DeltaH (the enthalpy change on denaturation at T(m), the midpoint of denaturation) is significantly less than DeltaH, the value obtained by the calorimetric measurements. If the analysis of thermal-denaturation curves assumes that the temperature-dependence of pre- and post-transition baselines is described by a parabolic function, there exists an excellent agreement between DeltaH(m) values of all proteins obtained from equilibrium and calorimetric methods. The latter analysis is supported by the studies on model compounds, for measurements of absorption properties of tyrosine, tryptophan and haem as a function of temperature suggested that the temperature-dependencies of the optical properties are indeed non-linear. We have observed that for each protein the constant-pressure heat-capacity change on denaturation (DeltaC(p)) determined from the plots of DeltaH versus T(m) is not only independent of the method of analysis of the transition curve, but it is also in excellent agreement with calorimetric DeltaC(p). An important conclusion of this study is that for these proteins that exhibit two-state character, all stability parameters are measured with the same error as that observed with a calorimeter.

Biochemistry↗
PubMed2000

Posterior capsule tear with plate-haptic silicone intraocular lens dislocation.

We report a case of posterior capsule rupture and posterior dislocation of an intraocular lens (IOL) caused by the tip of a silicone plate-haptic lens. The dislocation occurred during IOL implantation after uneventful phacoemulsification in a patient with a small pupil. Discussed are the possible reasons for the complication and measures to prevent it.

Aged↗
PubMed2000

Clinical features and pathogenesis of thyrotoxicosis in adult Melanesians in Papua New Guinea.

OBJECTIVE: To investigate the cause of an apparent increase in the incidence of thyrotoxicosis in the Melanesian population of the coastal areas around Port Moresby, Papua New Guinea. DESIGN: Consecutive patients attending the thyroid clinic at Port Moresby General Hospital were included in the study which collected clinical and immunogenetic data. PATIENTS: One hundred and ninety-four patients with thyrotoxicosis were studied. The mean age was 31 years. The clinical features were typical for thyrotoxicosis apart from increased pigmentation, which occurred in the majority of patients and which reversed with treatment with antithyroid drugs and resolution of the thyrotoxicosis. MEASUREMENTS: Antibodies to thyroid peroxidase, thyroglobulin and the thyrotropin receptor were present in 99%, 52% and 69% of patients, respectively, confirming that all cases were caused by autoimmune thyroid disease. Fine needle aspirations in 42 of 43 patients were consistent with Graves' disease. CONCLUSIONS: The cause of this apparent sudden increase in Graves' disease in the coastal region around Port Moresby, an apparently iodine-replete area, remains unexplained.

Adult↗
PubMed2000

Thyroid hormone receptor gene expression in first trimester human fetal brain.

Maternal thyroid hormone is transferred to the fetus early in pregnancy and is postulated to regulate brain development. Thyroid hormone nuclear receptor (TR) proteins are present in fetal brain, but their isoformal composition is unknown. We therefore investigated the ontogeny of TR isoforms and related splice variants in first trimester human fetal brain (n = 9) by semi-quantitative reverse transcriptase-polymerase chain reaction analysis. Expression of the TRbeta1, TRalpha1 and c-erbAalpha2 isoforms was detected from 8.1 weeks gestation (wg). An additional truncated species was detected with the c-erbAalpha2 primer set, consistent with the c-erbAalpha3 splice variant previously described in the rat. All c-erbAalpha-derived transcripts were co-ordinately expressed and increased (ca. 8-fold) between 8.1 and 13.9 wg. A more complex ontogenic pattern was observed for TRbeta1, suggestive of a nadir between 8.4 and 12.0 wg. These findings point to an important role for the TRalpha1 isoform in mediating maternal thyroid hormone action during first trimester human fetal brain development.

Adult↗
PubMed2000

Effects of cardiac glycosides on atrial contractile dysfunction after short-term atrial fibrillation.

BACKGROUND: Despite a long history of use in the treatment of paroxysmal atrial fibrillation (AF), the efficacy of cardiac glycosides has not been established. If such drugs are beneficial in this condition, the general view is that the benefit must be related to their inotropic actions. METHODS AND RESULTS: To assess the effects of the rapid-acting cardiac glycoside, acetylstrophanthidin (AS), on AF and AF-induced right atrial (RA) "stunning," RA wall motion (with ultrasonic crystals), RA pressure, and peak first derivative of pressure (dp/dt) (with microtip transducers) were measured before and after 5 min of high-intensity rapid atrial stimulation (10 Hz; 10 mA; 1 ms) and after the cessation of poststimulation AF. Measurements were made in neurally intact and autonomically blockaded dogs both before and after the administration of AS (0.01 mg/kg IV bolus and 0.015 mg/kg/h IV infusion). AS prevented the post-AF reduction in RA peak dp/dt under neurally intact and autonomically blockaded conditions, and it prevented the post-AF increase in the RA end-systolic dimension and the decrease in the percentage of RA systolic shortening with autonomic blockade. AS was beneficial whether or not baseline inotropy was enhanced by AS. The duration of AF following atrial stimulation was the same before and after AS, but when compared to controls, AS treatment appeared to prolong AF. CONCLUSIONS: Cardiac glycosides exert a favorable effect on AF-induced RA stunning, but this action is unrelated to its effects on the duration of AF.

Animals↗
PubMed2000

An overview of telemedicine: the virtual gaze of health care in the next century.

This article considers the role of telemedicine in the production of biomedical health care using three specific theoretical constructs as lenses through which to examine this phenomenon: (1) Foucault's medical "gaze"; (2) the political economy of health; and (3) deterritorialization and multisite ethnography. This examination focuses first on the changing corporate structure of health care and changing political attitudes toward telemedicine. Second, it documents the current use of telemedicine in prisons, the military, and in cross-cultural settings. Third, it discusses responses to telemedicine of individual physicians, health care staff, and patients, finding that these responses are broadly conditioned by an individual's mode of articulation with biomedical institutions and that they are mediated by personal experience.

Anthropology, Cultural↗
PubMed1999

Typhoid fever in children aged less than 5 years.

BACKGROUND: Calculation of the incidence of typhoid fever during preschool years is important to define the optimum age of immunisation and the choice of vaccines for public-health programmes in developing countries. Hospital-based studies have suggested that children younger than 5 years do not need vaccination against typhoid fever, but this view needs to be re-examined in community-based longitudinal studies. We undertook a prospective follow-up study of residents of a low-income urban area of Delhi, India, with active surveillance for case detection. METHODS: A baseline census was undertaken in 1995. Between Nov 1, 1995, and Oct 31, 1996, we visited 8172 residents of 1820 households in Kalkaji, Delhi, twice weekly to detect febrile cases. Blood samples were obtained from febrile patients, and those who tested positive for Salmonella typhi were treated with ciprofloxacin. FINDINGS: 63 culture-positive typhoid fever cases were detected. Of these, 28 (44%) were in children aged under 5 years. The incidence rate of typhoid per 1000 person-years was 27.3 at age under 5 years, 11.7 at 5-19 years, and 1.1 between 19 and 40 years. The difference in the incidence of typhoid fever between those under 5 years and those aged 5-19 years (15.6 per 1000 person-years [95% CI 4.7-26.5]), and those aged 19-40 years (26.2 [16.0-36.3]) was significant (p<0.001 for both). The difference between the incidence of typhoid at 5-19 years and the incidence at 19-40 years was also significant (10.6 [6.3-14.8], p<0.001). Morbidity in those under 5 and in older people was similar in terms of duration of fever, signs and symptoms, and need for hospital admission. INTERPRETATION: Our findings challenge the common view that typhoid fever is a disorder of school-age children and of adults. Typhoid is a common and significant cause of morbidity between 1 and 5 years of age. The optimum age of typhoid immunisation and the choice of vaccines needs to be reassessed.

Adolescent↗
PubMed1999

Chinese hamster ovary cell mutants defective in glycosaminoglycan assembly and glucuronosyltransferase I.

The proteoglycans of animal cells typically contain one or more heparan sulfate or chondroitin sulfate chains. These glycosaminoglycans assemble on a tetrasaccharide primer, -GlcAbeta1, 3Galbeta1,3Galbeta1,4Xylbeta-O-, attached to specific serine residues in the core protein. Studies of Chinese hamster ovary cell mutants defective in the first or second enzymes of the pathway (xylosyltransferase and galactosyltransferase I) show that the assembly of the primer occurs by sequential transfer of single monosaccharide residues from the corresponding high energy nucleotide sugar donor to the non-reducing end of the growing chain. In order to study the other reactions involved in linkage tetrasaccharide assembly, we have devised a powerful selection method based on induced resistance to a mitotoxin composed of basic fibroblast growth factor-saporin. One class of mutants does not incorporate 35SO4 and [6-3H]GlcN into glycosaminoglycan chains. Incubation of these cells with naphthol-beta-D-xyloside (Xylbeta-O-Np) resulted in accumulation of linkage region intermediates containing 1 or 2 mol of galactose (Galbeta1, 4Xylbeta-O-Np and Galbeta1, 3Galbeta1, 4Xylbeta-O-Np) and sialic acid (Siaalpha2,3Galbeta1, 3Galbeta1, 4Xylbeta-O-Np) but not any GlcA-containing oligosaccharides. Extracts of the mutants completely lacked UDP-glucuronic acid:Galbeta1,3Gal-R glucuronosyltransferase (GlcAT-I) activity, as measured by the transfer of GlcA from UDP-GlcA to Galbeta1,3Galbeta-O-naphthalenemethanol (<0.2 versus 3.6 pmol/min/mg). The mutation most likely lies in the structural gene encoding GlcAT-I since transfection of the mutant with a cDNA for GlcAT-I completely restored enzyme activity and glycosaminoglycan synthesis. These findings suggest that a single GlcAT effects the biosynthesis of common linkage region of both heparan sulfate and chondroitin sulfate in Chinese hamster ovary cells.

Animals↗
PubMed1999

Glycoside primers of Psittacanthus cucullaris.

Bioassay-directed chromatographic separation of the ethyl acetate extract of the whole plant of Psittacanthus cucullaris afforded a new phenolic xyloside, ellagic acid-4-O-beta-xyloside-3,3', 4'-trimethyl ether (1) together with four known compounds, ellagic acid-4-O-beta-xyloside-3,3'-dimethyl ether (2), gallic acid, beta-sitosterol, and beta-sitosterol beta-D-glucoside. The structure of the new compound was determined by spectroscopic methods. Like other beta-D-xylosides, compounds 1 and 2 stimulated the formation of glycosaminoglycan chains when fed to the cultured Chinese hamster ovary cells.

Animals↗
PubMed1999

African trypanosomiasis in two travelers from the United States.

African trypanosomiasis is a rare but well-documented cause of fever in United States travelers returning from areas where it is endemic. We report two recently diagnosed cases that involved tourists who went on safari in Tanzania. Review of these and 29 other published cases indicates that disease in returning United States travelers is nearly always of the East African form, a fulminant illness for which prompt diagnosis is necessary. In the United States, timely and appropriate therapy for this disease has resulted in favorable outcomes for most patients. Chemoprophylaxis for East African trypanosomiasis is not recommended, but travelers visiting areas of endemicity should practice appropriate preventive measures to prevent tsetse fly bites.

Female↗