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Biomedical subjects

P Gupta

Publications and source records attributed to P Gupta.

At least 145 records · Page 8Linked to original sources
PubMed1998

Human CD34(+) bone marrow cells regulate stromal production of interleukin-6 and granulocyte colony-stimulating factor and increase the colony-stimulating activity of stroma.

Cytokines produced by stromal cells induce the proliferation and differentiation of hematopoietic cells in the marrow microenvironment. We hypothesized that cross-talk between hematopoietic cells at different stages of differentiation and stromal cells influences stromal cytokine production and is responsible for maintaining steady-state hematopoiesis and responding to stress situations. We show that coculture of primitive CD34(+) cells in contact with or separated by a transwell membrane from irradiated human bone marrow stromal layers induces a fourfold to fivefold increase in interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) levels in the stromal supernatant (SN) during the first week. Levels of both cytokines decreased to baseline after coculture of CD34(+) cells for 3 to 5 weeks. Coculture of more mature CD15(+)/CD14(-) myeloid precursors induced only a transient 1.5- to 2-fold increase in IL-6 and G-CSF at 48 hours. Neither CD34(+) nor CD15(+)/CD14(-) cells produced IL-6, G-CSF, IL-1beta, or tumor necrosis factor alpha. When CD34(+) cells were cultured in methylcellulose medium supplemented with cytokines at concentrations found in stromal SN or supplemented with stromal SN, a fourfold to fivefold increase in colony formation was seen over cultures supplemented with erythropoietin (EPO) only. When cultures were supplemented with the increased concentrations of IL-6 and G-CSF detected in cocultures of stroma and CD34(+) cells or when CD34(+) cells were cocultured in methylcellulose medium in a transwell above a stromal layer, a further increase in the number and size of colonies was seen. The colony-forming unit-granulocyte-macrophage-stimulating activity of stromal SN was neutralized by antibodies against G-CSF or IL-6. These studies indicate that primitive CD34(+) progenitors provide a soluble positive feedback signal to induce cytokine production by stromal cells and that the observed increase in cytokine levels is biologically relevant.

Antigens, CD34↗
PubMed1998

Evolution of human immunodeficiency virus type 1 envelope sequences in infected individuals with differing disease progression profiles.

Sequence variation displayed by the human immunodeficiency virus type 1 (HIV-1) has been proposed to be linked to the pathogenesis of acquired immunodeficiency syndrome (AIDS). To assess viral evolution during the course of infection, we evaluated sequence variability in the env variable domains in four HIV-1-infected individuals exhibiting differing profiles of CD4+ T cell decline when followed from seroconversion until the development of AIDS or loss of followup. Proviral sequences encoding the V3-V5 region of gp 120 were obtained following PCR amplification of peripheral blood mononuclear cell DNA and cloning. Virus in each patient was relatively homogeneous early in infection and then diverged with time, more consistently at its nonsynonymous sites. Just prior to or coincident with a rapid decline in CD4+ T cell numbers, sequences were found with basic amino acid substitutions clustered within and downstream of the gp 120 V3 domain. Within the constraints of the current data set, we conclude that the virus appears to continually accumulate changes in its amino acid sequences well into the time of marked CD4+ T cell decline.

Amino Acid Sequence↗
PubMed1998

Incidence of neural axis abnormalities in infantile and juvenile patients with spinal deformity. Is a magnetic resonance image screening necessary?

STUDY DESIGN: A prospective and retrospective review of patients 10 years and younger with idiopathic scoliosis evaluated with a total spine magnetic resonance imaging (MRI) scan. OBJECTIVES: To determine the incidence of neural axis abnormalities in infantile and juvenile patients with idiopathic scoliosis without neurologic findings on history and examination, to determine the need for a screening MRI in this age group. SUMMARY OF BACKGROUND DATA: In previous studies, a 19.2% and 26% incidence of neural axis abnormalities were found in infantile and juvenile patients with "idiopathic" scoliosis, respectively, raising the question of routine MRI screening of the spinal canal in these patients. METHODS: A prospective study included 34 consecutive patients newborn to 10 years of age treated between 1992 and 1996 at a spinal deformity clinic with idiopathic scoliosis > 20 degrees without neurologic findings. In addition, a retrospective review of 64 patients age newborn to 10 years of age with idiopathic scoliosis was performed. All patients were evaluated by a total spine MRI protocol for examination of neural axis abnormalities. RESULTS: The incidence of neural axis abnormalities in the prospective group of 34 patients was 17.6% (6 of 34); the incidence of neural axis abnormalities was 20.3% (13 of 64) in the retrospective group. Of 6 patients in the infantile age range, 3 (50%) had neural axis abnormalities. CONCLUSIONS: A total spine MRI is recommended at presentation in patients with juvenile onset idiopathic scoliosis (> 20 degrees) because of the high incidence of neural axis abnormalities. Further study appears warranted to establish the incidence of neural axis abnormalities in infantile idiopathic scoliosis to determine the need for total spine MRI screening in this age group.

Arnold-Chiari Malformation↗
PubMed1998

Effect of denaturant and protein concentrations upon protein refolding and aggregation: a simple lattice model.

We present a study of the competition between protein refolding and aggregation for simple lattice model proteins. The effect of solvent conditions (i.e., the denaturant concentration and the protein concentration) on the folding and aggregation behavior of a system of simple, two-dimensional lattice protein molecules has been investigated via (dynamic Monte Carlo simulations. The population profiles and aggregation propensities of the nine most populated intermediate configurations exhibit a complex dependence on the solution conditions that can be understood by considering the competition between intra- and interchain interactions. Some of these configurations are not even seen in isolated chain simulations; they are observed to be highly aggregation prone and are stabilized primarily by the aggregation reaction in multiple-chain systems. Aggregation arises from the association of partially folded intermediates rather than from the association of denatured random-coil states. The aggregation reaction dominates over the folding reaction at high protein concentration and low denaturant concentration, resulting in low refolding yields at those conditions. However, optimum folding conditions exist at which the refolding yield is a maximum, in agreement with some experimental observations.

Models, Chemical↗
PubMed1998

Differential behavioral and endocrinological effects of corticotropin-releasing hormone (CRH) in the Syracuse high- and low-avoidance rats.

The Syracuse high- and low-avoidance rats, which have been selectively bred for good (SHA/Bru) or poor (SLA/Bru) avoidance learning in a two-way shuttle box, differ in emotionality. This experiment investigated the effect of corticotropin-releasing hormone (CRH), administered centrally (0, 0.1, 0.5, and 1.0 microg), on conditioned suppression and on the hypothalamic-pituitary-adrenocortical system. Three groups of animals were used: SHA/Bru rats conditioned at 0.21 or 0.43 mA and SLA/Bru rats conditioned at 0.21 mA. The results confirm those of previous studies which found that SLA/Bru rats show greater conditioned suppression than the SHA/Bru rats at the low shock intensity and that at 0.43 mA, the SHA/Bru animals acquire a level of conditioning comparable to that of the SLA/Bru animals at 0.21 mA. The results show that the nonlinear behavioral effect of CRH is independent of strain and produces comparable effects in animals of both strains, but only when level of conditioning is equated. Adrenal and plasma concentrations of corticosterone increased in all three groups of animals as a direct linear function of dose of CRH. Both greater levels of conditioning and larger amounts of CRH increase the synthesis of corticosterone more in SHA/Bru animals than in the SLA/Bru animals. Thus, genetic variation, which differentiates the behavioral and endocrinological characteristics of these animals, shows that these effects of CRH can be independent of each other and suggests that some minimal level of conditioned fear is necessary for CRH to exert its anxiogenic effect.

Acoustic Stimulation↗
PubMed1998

Interaction of calyx fluid and venom from Microplitis croceipes (Braconidae) on developmental disruption of the natural host, Heliocoverpa zea, and two atypical hosts, Galleria mellonella and Spodoptera exigua.

Polydnaviruses of many braconid and ichneumonid endoparasitoids play an important role in the successful parasitism of their hosts. The host's development is altered and its immune response is also suppressed. In this study, we compared the effects of calyx fluid and venom on the development of the natural host, Helicoverpa zea, and two atypical hosts that the parasitoid does not normally attack in nature, Galleria mellonella and Spodoptera exigua. The levels of calyx fluid and\or venom injected was 0.05, 0.1 and 0.2 female equivalents (FE)/larva. In H. zea, calyx fluid significantly reduced larval growth on day 5 post injection. Venom alone did not affect larval growth but it synergized the action of calyx fluid by reducing growth earlier and for a longer period after injection. Other effects of calyx fluid on the host, either alone or in combination with venom, were an increase in developmental period, and a reduction in percent emergence and weight of adult moths. The percentage of H. zea larvae that pupated was not affected by calyx fluid or venom. In Galleria mellonella, venom alone reduced larval growth comparable to calyx fluid and both tissues induced the effects on day 1 post injection. Other effects caused by calyx fluid or venom alone or the combination were a reduction in percent pupation and emergence, and the average adult weight. In S. exigua, high mortality occurred when 4th instar larvae were injected. Although the injection of larger fifth instars reduced overall mortality, the sham-injected larvae only gained weight during the first 24 hours after injection (from day 0 to day 1). However, adults were produced at all doses of calyx fluid or venom. The effects of the virus on development in this species were a prolongation of the larval stage and reduction of adult weight by calyx fluid in combination with venom. In conclusion, injections of calyx fluid and venom of Microplitis croceipes can differentially affect the growth and development of its natural host H. zea, and atypical host, G. mellonella, but only a minimal effect was observed in S. exigua.

Journal Article↗
PubMed1998

Current perspectives on pain upon injection of drugs.

A limitation in the administration of parenteral products is the pain caused upon injection. Injection site pain has been predominately associated with intravenous, intramuscular, and subcutaneous administration. It becomes important for the formulation scientist to have a basic understanding of the physiology underlying the pain process, as well as the pharmaceutical factors associated with injection site pain. Initially, this review will provide the reader with a primer on the mediation of pain in the periphery and a compilation of those drugs that have been associated with pain on injection. In addition, this review will present important considerations and general formulation approaches or methods that have been used to overcome pain on injection. Finally, a brief overview of the various experimental systems used to investigate injection site pain is discussed.

Humans↗
PubMed1998

Inhibition of postvitrectomy fibrin using troxerutin.

PURPOSE: To evaluate the efficacy of intraocular infusion of troxerutin in the inhibition of fibrin formation after vitrectomy in a rabbit model. METHODS: Lensectomies and vitrectomies were performed in a masked fashion on seven eyes treated with a 10-mM infusion of troxerutin and on seven control eyes that received only a balanced salt solution infusion. Masked grading of intraocular fibrin formation and intravitreal hemorrhage was performed for 1 week. RESULTS: On postoperative days 1 and 2, the control group exhibited a greater mean fibrin index (MFI) percentage than the troxerutin-treated group (day 1, 27.7% versus 19.5% MFI; day 2, 14.5% versus 6.1% MFI, respectively). On postoperative day 3, both groups showed an MFI of 1.8%. On postoperative days 5 and 7, both groups showed only minimal presence of fibrin. Neither of the two groups had an increased rate of intraocular hemorrhage. CONCLUSIONS: Infusion of 10 mM troxerutin resulted in a relative decrease in the amount of fibrin produced without an increased risk of intraocular hemorrhage in treated eyes compared with controls, but the difference was not statistically significant. Further studies may be warranted to evaluate the optimal dose of troxerutin alone or a possible role for its use in conjunction with other drugs employing a different mechanism of action in the prevention of fibrin formation.

Animals↗
PubMed1998

Leopard syndrome: a tropical rarity.

This is a case report of a classical presentation of the Leopard syndrome from the Indian subcontinent. The male patient had progressively increasing generalised multiple lentiginosis, ocular hypertelorism, pulmonary stenosis, short stature, cryptorchidism, and pectus excavatum. The case is documented for its rarity in this part of the world and typical clinical presentation.

Abnormalities, Multiple↗
PubMed1998

Expression and purification of the recombinant lethal factor of Bacillus anthracis.

The structural gene for the 90-kDa lethal factor (LF) isolated from Bacillus anthracis was expressed as a fusion protein with six histidine residues in Escherichia coli. Expression of LF in E. coli under the transcriptional regulation of the T5 promoter yielded a soluble cytosolic protein with an apparent molecular mass of 90 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Recombinant LF reacted with anti-LF antibodies. The protein was purified to homogeneity by nickel nitrilotriacetic acid affinity chromatography and gel filtration on a Sephacryl S-200 column followed by anion exchange on a fast-performance liquid chromatograph with a Resource-Q column. The yield of purified LF from this procedure was 1.5 mg/liter. In solution, trypsin cleaved protective antigen bound to native and recombinant LF with comparable affinities. In macrophage lysis assays, native and recombinant LF exhibited identical potencies. The results suggest that large amounts of biologically active LF can be purified by this procedure.

Animals↗
PubMed1998

Human immunodeficiency virus type 1 populations in blood and semen.

Transmission of human immunodeficiency virus type 1 (HIV-1) usually results in outgrowth of viruses with macrophage-tropic phenotype and consensus non-syncytium-inducing (NSI) V3 loop sequences, despite the presence of virus with broader host range and the syncytium-inducing (SI) phenotype in the blood of many donors. We examined proviruses in contemporaneous peripheral blood mononuclear cells (PBMC) and non-spermatozoal semen mononuclear cells (NSMC) of five HIV-1-infected individuals to determine if this preferential outgrowth could be due to compartmentalization and thus preferential transmission of viruses of the NSI phenotype from the male genital tract. Phylogenetic reconstructions of approximately 700-bp sequences covering the second constant region through the fifth variable region (C2 to V5) of the viral envelope gene revealed distinct variant populations in the blood versus the semen in two patients with AIDS and in one asymptomatic individual (patient 613), whereas similar variant populations were found in both compartments in two other asymptomatic individuals. Variants with amino acids in the V3 loop that predict the SI phenotype were found in both AIDS patients and in patient 613; however, the distribution of these variants between the two compartments was not consistent. SI variants were found only in the PBMC of one AIDS patient but only in the NSMC of the other, while they were found in both compartments in patient 613. It is therefore unlikely that restriction of SI variants from the male genital tract accounts for the observed NSI transmission bias. Furthermore, no evidence for a semen-specific signature amino acid sequence was detected.

Acquired Immunodeficiency Syndrome↗
PubMed1998

The biochemistry of gene therapy for AIDS.

Gene therapy has enormous potential and could in the near future involve the clinical biochemist in monitoring its efficacy. The involvement of clinical biochemists in this field could be not only in evaluating the impact of a gene-based strategy on disease progression, but also in measuring the expression of the products of therapeutic genes in treated individuals. Indeed, gene therapy presents new possibilities for the treatment of many diseases and, in particular, merits consideration in the treatment of a fatal disease like AIDS. The aim of this paper is to review the biochemical basis and clinical relevance of the gene therapy approaches directed towards the inhibition of human immunodeficiency virus type-1. We discuss the goals which have been achieved, the problems which have occurred and the efforts that are being made to solve them. In this regard, particular attention is paid to new strategies targeting 'therapeutic' enzymes to human immunodeficiency virus type-1 nucleic acids.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Educational status and dietary fat and anti-oxidant intake in urban subjects.

To assess correlation of dietary atherogenic and anti-atherogenic factors with socio-economic status (SES) we performed nutritional survey among 182 (122 men, 60 women) randomly selected individuals using 24 hour diet recall and a food-frequency questionnaire. SES was assessed by educational level which strongly correlated with occupational class (r = 0.55) and income levels (r = 0.88). There was significant (p < 0.05) positive correlation (r values) of educational level with intake of calories (0.55), proteins (0.19), fat (0.45), fat derived energy (en%) (0.14), saturated fat en% (0.45), linoleic acid (0.17), vitamin A (0.14), vitamin C (0.16), vitamin E (0.44), fruits and vegetables (0.34) and fibre (0.24) and negative correlation with intake of linolenic acid (-0.35), monounsaturated fat (MUFA) en% (-0.15), polyunsaturated fat (PUFA)/saturated fat (SFA) (-0.33) and MUFA/SFA (-0.42). In persons of highest educational level (> 15 years education) vs illiterates, the daily intake of SFA (29.1 +/- 15 vs 7.8 +/- 6), SFA en% (13.2 +/- 5 vs 6.7 +/- 4), linoleic acid en% (5.4 +/- 3 vs 3.9 +/- 2) and n6/n3 (24.0 +/- 58 vs 4.5 +/- 5) was more and intake of linolenic acid en% (0.7 +/- 1 vs 1.6 +/- 1), MUFA en% (8.6 +/- 7 vs 15.6 +/- 9), PUFA/SFA (0.6 +/- 1 vs 1.0 +/- 1) and MUFA/SFA (0.7 +/- 1 vs 4.0 +/- 5) was less. Intake of antioxidant vitamins A, C and E and fruits and vegetables was significantly more in better educated.

Adult↗
PubMed1998

Prevalence & etiology of nutritional anaemias in early childhood in an urban slum.

The present study was carried out to find out the prevalence and etiology of nutritional anaemia among preschool children from an urban slum. Randomly selected 300 children aged 3 months-3 yr were analysed over a period of one year for estimating prevalence of nutritional anaemia. Prevalence was also assessed by the rise in haemoglobin after 8 wk of haematinic supplementation in 159 of the 300 subjects. Ninety anaemic children were evaluated for the etiology of anaemia. Prevalence of anaemia, as judged by WHO recommended 'cut-off' value of haemoglobin < 11 g/dl, was 76 per cent while comparable value of 74.8 per cent was derived by response to haematinic supplementation. Pure iron deficiency anaemia (IDA) was detected in 41.4 per cent (37/90) of anaemic children. Vitamin B12 deficiency alone or in combination with iron was diagnosed in 14.4 and 22.2 per cent anaemic children respectively. Similarly folate deficiency, IDA with infection and anaemia of chronic diseases (ACD) was diagnosed in 2.2, 3.3 and 12.2 per cent cases respectively. Childhood anaemia continues to be a significant public health problem in preschoolers and iron deficiency is by far the commonest nutritional cause of anaemia. Vitamin B12 deficiency per se or in combination with iron is an important yet not commonly recognised cause of anaemias in preschool children in the community.

Anemia↗