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Biomedical subjects

S Tiwari

Publications and source records attributed to S Tiwari.

At least 37 records · Page 2Linked to original sources

The latex agglutination test: standardization and comparison with direct agglutination and dot-ELISA in the diagnosis of visceral leishmaniasis in India.

Laboratory diagnosis of visceral leishmaniasis (VL) is usually based on the detection of Leishmania amastigotes in samples of bone marrow or splenic aspirate obtained by invasive procedures. Serological tests serve as a useful adjunct and are especially valuable in early or highly immune cases where amastigotes may be too scanty to be seen easily. The direct agglutination test (DAT) is generally considered the most suitable of the four types of tests currently employed (IFAT, counter immuno-electrophoresis, ELISA and DAT). However, the latex agglutination test (LAT) was recently reported to be a rapid and sensitive screening tool for VL and one which could be carried out at the patient's bedside. Further standardization and evaluation of LAT has now revealed that although it is comparable with DAT and dot-ELISA in terms of sensitivity it is far inferior because of cross-reactivity with other infections. This lack of specificity makes LAT unsuitable for routine diagnosis of VL even though it is rapid and sensitive. DAT still appears to be the best choice as a diagnostic tool, as it is very specific and does not require expensive equipment or reagents or much technical competence and the result can be visually interpreted. These merits make DAT very suitable for the diagnosis of VL in endemic areas of India.

Agglutination Tests↗

MEICPS: substitution mutations to engineer intracellular protein stability.

UNLABELLED: In MEICPS, results from earlier analyses are utilized to suggest possible substitution point mutations to engineer intracellular stability using a given sequence or structure of the protein. AVAILABILITY: From bvbreddy@ccmb.ap.nic.in. This program needs data from other software, PSA and SSTRUC, available from sali@tamika.rockefeller.edu and tom@cryst.bioc.cam.ac.uk, respectively. CONTACT: bvbreddy@ccmb.ap.nic.in

Computational Biology↗

Use of propensities of amino acids to the local structural environments to understand effect of substitution mutations on protein stability.

Advances in site-directed mutagenesis and other genetic engineering techniques have made it possible to create novel proteins of interest. A challenging aspect of these studies is to understand the effect of substitution mutations on folding and stability of natural proteins. We present an analysis of protein structure data, available from the literature, for which substitution mutations have been made and changes in stability characteristics are reported. Amino acid structural environment parameters have been computed for a set of 304 non-homologous best resolved protein structures. The structural environment parameters were used to calculate each of the 20 amino acid propensities to a given structural environment. The observed increase or decrease in stability upon mutation was found to be correlated with the average residue structural environment propensity of wild-type residue versus mutant residue. The analysis presented here helps identification of less optimally placed residues in a given protein structure, and suggests possible substitution mutations to a residue with higher propensity to the corresponding local structural environment. We propose that such substitution mutations, suggested based on amino acid propensities to local structural environments, should bestow higher stability to the protein structure.

Amino Acid Substitution↗

Pulmonary functions in Indian sportsmen playing different sports.

Regular exercise has proved to be beneficial for the human body and the lungs are no exception. The present study was undertaken to assess the relation between the quality of exercise performed and the quantitative effect of these exercises on the lungs. Pulmonary function tests of sportsmen engaged in various sports were compared with each other and with that of the controls. Players playing football (n=18), hockey (n=19), volleyball (n=20), swimming (n=20) and basketball (n=18) were chosen for this study. Medical students (n=20) were chosen as controls. The parameters taken into account in this study were forced vital capacity (FVC), forced expiratory volume (FEV-1), and peak expiratory flow rate (PEFR). The results indicate that all the sportspersons had a higher values of lung functions compared to the controls. Among the various groups of players chosen for this study, the swimmers showed the maximum increase in their lung functions.

Adult↗

Prediction of probable genes by Fourier analysis of genomic sequences.

MOTIVATION: The major signal in coding regions of genomic sequences is a three-base periodicity. Our aim is to use Fourier techniques to analyse this periodicity, and thereby to develop a tool to recognize coding regions in genomic DNA. RESULT: The three-base periodicity in the nucleotide arrangement is evidenced as a sharp peak at frequency f = 1/3 in the Fourier (or power) spectrum. From extensive spectral analysis of DNA sequences of total length over 5.5 million base pairs from a wide variety or organisms (including the human genome), and by separately examining coding and non-coding sequences, we find that the relative-height of the peak at f = 1/3 in the Fourier spectrum is a good discriminator of coding potential. This feature is utilized by us to detect probable coding regions in DNA sequences, by examining the local signal-to-noise ratio of the peak within a sliding window. While the overall accuracy is comparable to that of other techniques currently in use, the measure that is presently proposed is independent of training sets or existing database information, and can thus find general application. AVAILABILITY: A computer program GeneScan which locates coding open reading frames and exonic regions in genomic sequences has been developed, and is available on request.

Algorithms↗

A study of peripheral nerve function in neonates and infants.

Motor and sensory nerve conduction velocity, H-reflex and F-response have been studied in the age group showing maximum changes i.e. neonates and infants. The nerve conduction velocity in upper and lower limbs was 25 M/S and 23.75 M/S respectively in neonate age group; 34.4 M/S and 32.4 M/S respectively in infant group. A significant relationship of age with nerve conduction parameters (velocity, terminal latency) has been observed in infants group but not so in neonate group. H-reflex (late response) was elicited in both Abductor Pollicis Brevis and Soleus. It was present in small muscles of hand (i.e. APB) in all the neonates and 55% of the infants only. This could be attributed to immaturity of nervous system. However, in the lower limb, H-reflex could be elicited in 100% of infants and neonates. In the present study, the relationship of age and height with different nerve conduction parameters as well as H-reflex (latency) has been highlighted.

Aging↗

Quality of life survey among long-stay mentally ill patients: patient and staff perspectives.

In order to improve the quality of life of the chronically mentally ill patients, their treatment programmes must be individualised to address their multiple disabilities and social impairment. The patient's perception of his quality of life (QoL) can be used as an organising framework for long-term care. Subjects in the study included staff and inpatients from the 10 rehabilitation wards in New Woodbridge Hospital which offers a wide range of rehabilitation activities. Using subjective indices, patient and staff perception of patients' quality of life were compared across several life domains. Significant differences between the 2 groups were noted in areas including living conditions, relationship with others and sense of purpose in life. Most patients found the new hospital a better place in terms of its physical comfort and the medical and psychiatric care received. The implications of these findings for improving existing care for our patients are discussed.

Chronic Disease↗

Inhibitors of blood platelet cAMP phosphodiesterase: a QSAR analysis.

A quantitative structure-activity relationship (QSAR) analysis of two related series of the derivatives of 7-substituted imidazo [4,5-b]-quinolin-2-one active as inhibitors of human blood platelet cAMP phosphodiesterase (PDE) is presented with a view to reflecting upon the parametric requirements of the side chain as well as of the N-1 and N-3 substitutions on the heterocycle. For the first series (Figure 1) consisting of 114 congeners and having a more flexible functionalized side chain at the 7-position and only binary variations (Me or H) at N-1 and N-3, it has been shown that bulk (Vw), of the functionalized side chain tends to potentiate the inhibitory activity of a derivative while positions N-1 and N-3 should better remain unsubstituted, as reflected through the dummy variables. A similar analysis of the compounds of the second series (Figure 2), where a less flexible side chain is linked through a basic nitrogen, has provided a parabolic dependence of inhibition activity on Vw. From this relationship, a limiting size of the side chain, seems to be necessary for triggering a minimal response.

3',5'-Cyclic-AMP Phosphodiesterases↗

Into and out of G1: the control of cell proliferation.

Progression of cells through G1 is an orderly process which is regulated by a series of key proteins. Over the past few years a number of these proteins have been identified and their mode of action has been studied in detail. This review will concentrate on the current knowledge about the function in G1 of cyclins, cyclin dependent kinases, the retinoblastoma protein and other related 'pocket' proteins. Mutations or deregulation of some of these proteins confer a growth advantage and their role in malignant transformation will be discussed.

Animals↗

Graft-versus-host disease following interferon therapy for relapsed chronic myeloid leukaemia post-allogeneic bone marrow transplantation.

The combination of donor leucocytes, with or without interferon, has produced encouraging responses in patients with haematological relapse following allogeneic BMT for chronic myeloid leukaemia (CML). A 25-year-old male received low-dose interferon-alpha alone for haematological relapse occurring 10 months following an allogeneic BMT for Ph-positive CML. Interferon therapy was complicated by severe GVHD requiring immunosuppressive therapy. The patient was subsequently found to be in complete haematological and cytogenetic remission, raising the possibility of an immune-mediated antileukaemic action.

Adult↗

Neonatal behavior in full-term small for date.

Fifty newborns, 25 full term SFDs (small for date) and 25 full term AGAs (appropriate for gestational age) were taken up for comparative study of their behavior using BNBAS (Brazelton's neonatal behavior assessment scale). The study revealed that full term SFDs performed significantly poorly on all items under cluster interactive processes compared to their counterparts full term AGAs on day 1. They also showed similar poor performance in clusters of motor processes and organizational processes (State control). Follow up assessment on day 30 revealed significantly better performance in these clusters. However, the performance of SFD babies in all items of cluster of organizational processes (physiological response) was comparable to that of AGA babies in the initial as well as follow up assessments.

Birth Weight↗

A quantitative structure-activity relationship study of ligands exhibiting agonist and antagonist actions with cholecystokinin-receptors.

Observed biological activities of substituted phenyl urea/thiourea tetrapeptides as agonists with the cholecystokinin-alimentary canal (CCK-A) receptor, and (R)-4-benzamido-5-oxopentanoic acid derivatives with both peripheral (CCK-A) and the central (CCK-B) (brain) receptors have been shown to be correlated with various physicochemical, e.g. pi, sigma, and structural, e.g. Vw and dummy, I, parameters. These results were, then interpreted to predict promising criteria for having ligands with better affinity with the CCK receptors.

Amino Acid Sequence↗

A quantitative analysis of binding affinities of ligands active at adenosine receptors.

Binding affinities, pKi's, of 1,3-dipropyl-8-phenylxanthines and 8-substituted xanthines as selective antagonists at A(1)- and A(2)- adenosine receptors, were quantitatively analysed in terms of hydrophobic parameter, pi, and van der Waals volume, Vw. For ligands of the first series, the hydrophobicity of para-substituents and the bulk of meta-substituents are shown to be the deciding factors. Similarly, for the other series, the binary substitutions at X-, Y- and R-positions, highlighted by respective dummy variables, and the bulk rendered by groups at R(1)-position, are found to be significantly correlated with A(1)- and A(2)-receptor affinities. Additionally, the Free-Wilson study of this series resulting into individual substituent contribution, provides similar inferences to these, but in a more exact manner. This study also hints at the possibility of a different accommodation site at the receptor for the R(1)-substituents of the congeners on account of conformational dissimilarity of A(1)- and A(2)-receptors.

Chemical Phenomena↗

Quantitative structure-activity relationship study of some benzodiazepine-receptor ligands having inverse agonist/antagonist and agonist actions.

Quantitative structure-activity relationship (QSAR) analyses of three different series of benzodiazepine ligands, pyridodiindoles, and beta-carbolines, having inverse agonist/antagonist and agonist actions have been performed with a view to understanding their likely mode of action at the benzodiazepine-receptor (BzR). From this study, the in vitro radioligand displacement activities of substituted 7,12-dihydropyrido[3,2-b: 5,4-b']diindoles (Figure 1) were found to be significantly correlated with resonance effect of R-substituents, van der Waals volumes at positions-1 and -3, hydrophobic constant at position-2 and field effect at position-4 of X-substituents. For 3-substituted beta-carbolines, a similar analysis has established that R-substituents at position-3 of beta-carbolines (Figure 2) are involved in strong hydrophobic interaction with some hydrophobic pocket on the receptor. For the analogues of 6-(benzyloxy)-4-(methoxymethyl)-beta-carbolines-3-carboxylic acid ethyl ester (Figure 3), however, the combined hydrophobicities of 6- and 4-substituents were shown to be important in determining ligand binding behaviour. The significant correlations so obtained are in agreement with the proposed models (Figures 4 and 5) of pharmacophores of inverse agonist/antagonist and of agonist sites at the BzR.

Carbolines↗

Schmidt's syndrome: a rare cause of puberty menorrhagia.

Schmidt's syndrome, also known as polyglandular deficiency syndrome, is the presence of Addison's disease and hypothyrodism in a single patient. It is usually associated with other autoimmune disorders like vitiligo, diabetes mellitus, myasthenia gravis. A rare case of an 18-year-old girl having Schmidt's syndrome and vitiligo who presented with puberty menorrhagia is reported. A brief review of the literature is also given.

Addison Disease↗