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Biomedical subjects

A Pande

Publications and source records attributed to A Pande.

At least 19 recordsLinked to original sources
PubMed2005

The glycosylation pattern of baculovirus expressed envelope protein E2 affects its ability to prevent infection with bovine viral diarrhoea virus.

We have investigated the role of glycosylation of the envelope glycoprotein E2 of bovine viral diarrhoea virus (BVDV), produced in insect cells, in BVDV infection. When amino acids predicated to code for the C-terminal N-linked glycosylation site were mutated the resulting protein was less efficient than wild type protein at preventing infection of susceptible cells with BVDV. In addition, mutational analysis showed that a further two predicted N-terminal N-linked glycosylation sites of E2 are required for efficient production of recombinant protein.

Animals↗
PubMed2001

Enhanced crystallization of the Cys18 to Ser mutant of bovine gammaB crystallin.

The cysteine residues of the gamma crystallins, a family of ocular lens proteins, are involved in the aggregation and phase separation of these proteins. Both these phenomena are implicated in cataract formation. We have used bovine gammaB crystallin as a model system to study the role of the individual cysteine residues in the aggregation and phase separation of the gamma crystallins. Here, we compare the thermodynamic and kinetic behavior of the recombinant wild-type protein (WT) and the Cys18 to Ser (C18S) mutant. We find that the solubilities of the two proteins are similar. The kinetics of crystallization, however, are different. The WT crystallizes slowly enough for the metastable liquid-liquid coexistence to be easily observed. C18S, on the other hand, crystallizes rapidly; the metastable coexisting liquid phases of the pure mutant do not form. Nevertheless, the coexistence curve of C18S can be determined provided that crystallization is kinetically suppressed. In this way we found that the coexistence curve coincides with that of the WT. Despite the difference in the kinetics of crystallization, the two proteins were found to have the same crystal forms and almost identical X-ray structures. Our results demonstrate that even conservative point mutations can bring about dramatic changes in the kinetics of crystallization. The implications of our findings for cataract formation and protein crystallization are discussed.

Amino Acid Substitution↗
PubMed2001

Crystal cataracts: human genetic cataract caused by protein crystallization.

Several human genetic cataracts have been linked recently to point mutations in the gammaD crystallin gene. Here we provide a molecular basis for lens opacity in two genetic cataracts and suggest that the opacity occurs because of the spontaneous crystallization of the mutant proteins. Such crystallization of endogenous proteins leading to pathology is an unusual event. Measurements of the solubility curves of crystals of the Arg-58 to His and Arg-36 to Ser mutants of gammaD crystallin show that the mutations dramatically lower the solubility of the protein. Furthermore, the crystal nucleation rate of the mutants is enhanced considerably relative to that of the wild-type protein. It should be noted that, although there is a marked difference in phase behavior, there is no significant difference in protein conformation among the three proteins.

Cataract↗
PubMed2001

Defibrillation via the elimination of spiral turbulence in a model for ventricular fibrillation.

Ventricular fibrillation, the major reason behind sudden cardiac death, is turbulent cardiac electrical activity in which rapid, irregular disturbances in the spatiotemporal electrical activation of the heart make it incapable of any concerted pumping action. Methods of controlling ventricular fibrillation include electrical defibrillation as well as injected medication. Electrical defibrillation, though widely used, involves subjecting the whole heart to massive, and often counterproductive, electrical shocks. We propose a defibrillation method that uses a very low-amplitude shock (of order mV) applied for a brief duration (of order 100 ms) and over a coarse mesh of lines on our model ventricle.

Defibrillators, Implantable↗
PubMed2000

PANORAMA: an integrated Web-based sequence analysis tool and its role in gene discovery.

As the exponential growth of DNA sequence information in databases continues, the task of converting this deposited information into knowledge becomes more dependent on integrative sequence analysis and visualization tools. PANORAMA is an Internet-accessible software package that performs a variety of informatics analyses on a given DNA sequence and returns a visual and interactive representation of the results. Its design is modular, so that further sequence analysis tools can be integrated with minimal effort. The utility of PANORAMA is demonstrated in the analysis of 650 kb of human genomic DNA from chromosome region 3p21.3, a region of potential tumor suppressor genes involved in lung cancer, breast cancer, and other forms of cancer. PANORAMA aided in the discovery of genes and alternate splice forms of known exons, in the demarcation of intron-exon boundaries, and in the identification of promoter regions and polymorphisms, all of which contributed to a better understanding of the region. PANORAMA is available on the World Wide Web at http://atlas.swmed.edu.

Animals↗
PubMed2000

Molecular basis of a progressive juvenile-onset hereditary cataract.

In a recent paper, patients with a progressive juvenile-onset hereditary cataract have been reported to have a point mutation in the human gammaD crystallin gene (Stephan, D. A., Gillanders, E., Vanderveen, D., Freas-Lutz, D., Wistow, G., Baxevanis, A. D., Robbins, C. M., VanAuken, A., Quesenberry, M. I., Bailey-Wilson, J., et al. (1999) Proc. Natl. Acad. Sci. USA 96, 1008-1012). This mutation results in the substitution of Arg-14 in the native protein by a Cys residue. It is not understood how this mutation leads to cataract. We have expressed recombinant wild-type human gammaD crystallin (HGD) and its Arg-14 to Cys mutant (R14C) in Escherichia coli and show that R14C forms disulfide-linked oligomers, which markedly raise the phase separation temperature of the protein solution. Eventually, R14C precipitates. In contrast, HGD slowly forms only disulfide-linked dimers and no oligomers. These data strongly suggest that the observed cataract is triggered by the thiol-mediated aggregation of R14C. The aggregation profiles of HGD and R14C are consistent with our homology modeling studies that reveal that R14C contains two exposed cysteine residues, whereas HGD has only one. Our CD, fluorescence, and differential scanning calorimetric studies show that HGD and R14C have nearly identical secondary and tertiary structures and stabilities. Thus, contrary to current views, unfolding or destabilization of the protein is not necessary for cataractogenesis.

Adolescent↗
PubMed2000

Spatiotemporal chaos and nonequilibrium transitions in a model excitable medium

We present a detailed study of the statistical steady states of a model for CO oxidation on Pt(110) proposed by Bar and co-workers. We show that the stability diagram of this model depends sensitively on the boundary conditions. We elucidate several novel properties of a state with meandering spirals (M) briefly mentioned by Bar and co-workers. (1) We show that, with periodic boundary conditions, M is the state MP, a binary mixture displaying a coexistence of quasiperiodically rotating spirals and chaotically moving pointlike defects. We show that the transition from MP to the turbulent state T1 is continuous; the transition line marks the locus where the two phases cease to be distinct. (2) With Neumann boundary conditions M is the state MN, a single quasiperiodically rotating spiral. We show that the MN-T1 transition is discontinuous or first order. We also characterize the transitions from MP and MN to the state S, which has quasiperiodically rotating spirals. We also propose qualitative mechanisms for these transitions.

Journal Article↗
PubMed1998

Computerized polymorphic marker identification: experimental validation and a predicted human polymorphism catalog.

A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called POMPOUS (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by POMPOUS to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75%) of the tumor lines using these markers. POMPOUS provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use POMPOUS to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved.

Computer Communication Networks↗
PubMed1998

ZFX and ZFY loci in water buffalo (Bubalus bubalis): potential for sex identification.

In the present study a small region of ZFX and ZFY loci in buffalo have been amplified by polymerase chain reaction (PCR). Restriction fragment length polymorphism (RFLP) was also uncovered that can distinguish between male and female buffalo DNA. The study also found a second copy of the ZFX loci (ZFXR) present in both male and female. Sequence analysis showed that ZFXR has a single base deletion that results in a redundant putative protein.

Amino Acid Sequence↗
PubMed1997

Drug use in Nepal: the view from the street.

This study uses qualitative research techniques to examine heroin use in Nepal. It explores the life histories of 16 heroin users in Kathmandu, the country's capital, emphasizing those who are street children or who are otherwise displaced. The cases document that the initiation of use in Nepal is a complex process which includes: certain personality traits; an early history of culturally acceptable use of alcohol, tobacco, marijuana, or hashish; peer influence; and the specific social setting of users. Outside (i.e., foreign) influences are included in the mix, but never as a single determinant of drug use. Factors specific to the Nepali scene include the traditional association of forms of marijuana with certain religious contexts and the availability of heroin. An additional factor is the poverty of the urban setting. The approach in Nepal to dealing with drugs primarily involves a realization of the role played by the interaction between personality and social setting in the fullest meaning of that term.

Adolescent↗
PubMed1995

Coronary angioplasty for the control of intractable ventricular arrhythmia.

Ventricular arrhythmias (VAs) that occur following an acute extensive anterior myocardial infarction (MI) usually respond to conventional antiarrhythmic regimes of treatment. Rarely, the VA may prove intractable to therapy. This report is of three patients who presented at varying time frames (3 h to 10 weeks) following an anterior MI. They exhibited sustained monomorphic ventricular tachycardia and hemodynamic instability despite multiple antiarrhythmic drug therapy, intravenous magnesium, direct-current cardioversion (DCCV), overdrive pacing (in one case), and intra-aortic balloon counterpulsation (IABP). Although there was no clinical evidence of continuing ischemia and although coronary angiography that was done in each case showed the infarct-related artery (IRA) to subtend akinetic areas on left ventricular (LV) angiogram, percutaneous transluminal coronary angioplasty (PTCA) of the IRA was done in all three cases. Reestablishing patency of the IRA helped in controlling the VA dramatically with average therapeutic doses of antiarrhythmic drugs. All three patients showed this control to have been maintained over a follow-up period of more than 1 year, with partial improvement in LV function and signal-averaged electrocardiogram negative for late potentials. Thus, in patients with extensive infarction and intractable VA, PTCA of the IRA may provide control of VA even in the absence of clinical signs of active ischemia or viable muscle mass.

Angioplasty, Balloon, Coronary↗
PubMed1994

Increased evening activation of the hypothalamic-pituitary-adrenal axis in depressed patients.

OBJECTIVE: To determine whether depressed patients demonstrate hypothalamic-pituitary-adrenal (HPA) axis activation during the late afternoon and evening, a time when the HPA axis is usually quiescent in normal subjects. METHODS: We administered metyrapone, an 11-beta-hydroxylase inhibitor of cortisol synthesis, to normal controls and depressed patients between 4 and 10 PM. Metyrapone blockade of cortisol secretion would amplify any HPA axis secretion. RESULTS: In 10 normal control subjects, administration of metyrapone lowered plasma cortisol levels to a mean of 36 nmol/L. No rebound corticotropin or beta-endorphin secretion was seen in these normal controls between 4 and 10 PM, supporting the existence of a period of minimal endogenous corticotropin releasing factor drive. Compared with a group of placebo-treated depressed patients (n = 10), metyrapone-treated depressed subjects (n = 17) had significantly decreased plasma cortisol concentrations. However, in contrast to normal controls treated with metyrapone, metyrapone-treated depressed patients demonstrated rebound corticotroph secretion, particularly between 7:30 and 10 PM (P = .036 for patients vs normal controls for beta-endorphin secretion from 4:30 to 10 PM). CONCLUSION: These data support the hypothesis of increased corticotropin releasing factor drive in the evening in depressed subjects and are in agreement with the longstanding observation of "early escape" from dexamethasone suppression between 4 and 11 PM in depressed patients.

Adrenocorticotropic Hormone↗
PubMed1992

Intermolecular protein interactions in solutions of calf lens alpha-crystallin. Results from 1/T1 nuclear magnetic relaxation dispersion profiles.

From analyses of the magnetic field dependence of 1/T1 (NMRD profiles) of water protons in solutions of calf lens alpha-crystallin at several concentrations, we find two regimes of solute behavior in both cortical and nuclear preparations. Below approximately 15% vol/vol protein concentration, the solute molecules appear as compact globular proteins of approximately 1,350 (cortical) and approximately 1,700 (nuclear) kD. At higher concentrations, the effective solute particle size increases, reversibly, as evidenced by the appearance of spectra-like 14N peaks in the NMRD profiles and a change in the field and temperature dependence of 1/T1. At these higher concentrations, the profiles are very similar to those of calf gamma II-crystallin, a crystallin that undergoes an analogous transition near approximately 15% protein (Koenig, S. H., C.F. Beaulieu, R. D. Brown III, and M. Spiller, 1990. Biophys. J. 57:461-469). By comparison with recent analyses of NMRD results for solutions of immobilized proteins as models for the transition from protein solutions to tissue (Koenig, S. H., and R. D. Brown III. 1991. Prog. NMR Spectr. 22:487-567), we argue that alpha-crystallin solute behaves as aggregates approximately greater than 50,000 kD as protein concentration is progressively increased above 15%. Finally, the concentration dependence of the NMRD profiles of alpha- and gamma II-crystallin can readily explain recent osmotic pressure data, in particular the intersection of the respective pressure curves at approximately 23% vol/vol (Vérétout, F., and A. Tardieu. 1989. Eur. Biophys. J. 17:61-68).

Animals↗
PubMed1992

A longitudinal evaluation of dexamethasone pharmacokinetics in depressed patients and normal controls.

Ten depressed patients and eight control subjects received 1 mg of dexamethasone intravenously at two different time points. Depressed patients were studied when they were depressed and following an improvement in their depression. In control subjects the first and second studies were performed approximately 1 month apart. Dexamethasone and cortisol were determined at 0, 5, 15, and 30 minutes, then at 1, 1.2, 2, 3, 4, 5, 6, 7, 9, 12, 17, and 24 hours following dexamethasone administration. Data from each patient was fit using a computer to a two compartment pharmacokinetic model and area under the time versus plasma concentration curve, elimination half-life, and clearance were also determined. Depressed patients exhibited a slower dexamethasone clearance and a larger area under the curve than control subjects at the first time point, but not at the second time point. The groups did not differ significantly in any of the other pharmacokinetic parameters (including distribution half-life, elimination half-life, or volume of distribution) at either time point. The possible causes and implications of these findings are discussed.

Adult↗
PubMed1991

An Indian hospital study of viral causes of acute respiratory infection in children.

From Sept. 1986 to Jan. 1989, a hospital-based study was conducted on 736 children, under 5 years of age, with acute respiratory infection. Nasopharyngeal secretions were examined for viruses by culture and by immunofluorescence. Viruses were detected in 22% of specimens: respiratory syncytial (5%), parainfluenza (5%), influenza A (4%), influenza B (2%), adenovirus (3%), measles (3%). The highest rates of detection were with patients diagnosed clinically as pneumonia or upper respiratory tract infection. The case fatality rate was very high (43%) in children with measles virus infection.

Child, Preschool↗
PubMed1990

Viral aetiology of acute respiratory infections in children in north India.

Two hundred and thirty children clinically diagnosed as suffering from acute respiratory infection were tested for four major groups of viral aetiological agents, i.e. influenza para-influenza, respiratory syncytial virus (RSV) and adenoviruses using indirect immunofluorescence technique. At least one of the respiratory viruses was identified in 51 (22 per cent) specimens, which included influenza A in 6 (3 per cent), influenza B in 3 (1 per cent), para-influenza type 1 in 3 (1 per cent), para-influenza type 3 in 13 (6 per cent), RSV in 11 (5 per cent) adenovirus in 12 (5 per cent), and dual virus infections in 3 (1 per cent) cases. Maximum number of virus identification was noted in children below 1 year of age, particularly infection with RSV followed by para-influenza and adenoviruses. Value of rapid diagnosis by indirect immunofluorescence technique is stressed.

Child, Preschool↗
PubMed1990

A longitudinal evaluation of dexamethasone and cortisol plasma concentrations in the dexamethasone suppression test before and during treatment with antidepressant drugs.

Thirty depressed in- and outpatients received serial dexamethasone suppression tests (DSTs). Plasma dexamethasone and cortisol concentrations were drawn at 1600 on the day following a 1-mg oral dose of dexamethasone. The first DST was performed after patients were drug-free for a period of 1 week; the second, third, and fourth DSTs while patients received antidepressant medication. Dexamethasone and cortisol concentrations drawn in the drug-free period correlated significantly. The cortisol to dexamethasone ratio changed significantly with time in DST nonsuppressors, suggesting that nonsuppression is associated with an altered pharmacodynamic response of the hypothalamopituitary-adrenal axis to dexamethasone during depression. When dexamethasone concentrations from the drug-free period were compared with those drawn during antidepressant treatment, no significant differences were noted.

Adult↗