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Biomedical subjects

P Gupta

Publications and source records attributed to P Gupta.

At least 127 records · Page 7Linked to original sources
PubMed1999

Binding and displacement of vascular endothelial growth factor (VEGF) by thrombospondin: effect on human microvascular endothelial cell proliferation and angiogenesis.

Vascular endothelial growth factor (VEGF) is a specific angiogenic factor, and thrombospondin (TSP), is a potent inhibitor of angiogenesis. To better understand the role of TSP as an anti-angiogenic agent, we have identified its specific domains that participate in its anti-angiogenic activity and examined the mechanism of its inhibitory effect on VEGF(165) induced angiogenesis. Exogenously added TSP inhibited VEGF(165) induced angiogenesis (proliferation and tube formation of human dermal microvascular endothelial cells [HDMEC] and neovascular outgrowth from human arterial rings). Although both VEGF(165) and TSP are heparin binding proteins, TSP had a higher affinity for (125)I-heparin than VEGF(165) (K(d1) 4 nM and K(d2) 14 nM for TSP; K(d) 91 nM for VEGF(165)). TSP displaced 36% of (125)I-VEGF(165) from HDMEC and this was comparable to the 27% reduction in (125)I-VEGF(165) binding to HDMEC upon cleavage of cell surface heparan sulfate (HS). About 35% of the mitogenic activity of VEGF(165) was attributable to its heparin binding region. These results indicate that a proportion of the mitogenic activity of VEGF(165) is inhibited by TSP via competition for cell surface HS. Further, (125)I-VEGF(165) bound directly to TSP in a saturable, concentration dependent manner, and heparin modulated this binding. The mAbs to the heparin binding domain to the type 1 and type 3 repeats of TSP inhibited the binding of VEGF(165) to TSP, and also blocked the inhibitory effect of TSP on VEGF(165) induced HDMEC proliferation. We conclude that (i) the anti-angiogenic activity of TSP is localized in its heparin binding domain and type 1 and type 3 repeats (ii) TSP inhibits angiogenesis by at least two separate mechanisms, (a) displacement of VEGF(165) from endothelial cell HS and (b) direct binding to VEGF(165).

Journal Article↗
PubMed1999

Efficacy of supratarsal dexamethasone versus triamcinolone injection in recalcitrant vernal keratoconjunctivitis.

PURPOSE: To compare the efficacy of supratarsal injection of short acting dexamethasone sodium phosphate versus intermediate acting triamcinolone acetonide as a new therapeutic modality for treating eyes with recalcitrant vernal keratoconjunctivitis (VKC). METHODS: The study was a prospective, randomized, double blind, case controlled trial, including 38 eyes of 19 patients with recalcitrant VKC. Except for two initial patients who received supratarsal injection of triamcinolone acetonide in both the eyes, one eye of each patient was randomly assigned to receive either 2 mg of dexamethasone sodium phosphate or 20 mg of triamcinolone acetonide. RESULTS: Both the drugs were equally effective with no statistically significant difference in the mean time of resolution of cobblestone papillae, limbal edema, shield ulcer, SPK and relief of symptoms. The recurrence rate of disease was, however, lower following triamcinolone acetonide injection. CONCLUSIONS: Supratarsal injection of corticosteroid is a cheap, effective and safe modality of treatment for managing eyes with recalcitrant VKC. Both short acting dexamethasone and intermediate acting triamcinolone acetonide are equally effective.

Adolescent↗
PubMed1999

Fas ligand expression in the bone marrow in myelodysplastic syndromes correlates with FAB subtype and anemia, and predicts survival.

Increased apoptosis in the bone marrow (BM) may contribute to the cytopenias that occur in myelodysplastic syndromes (MDS). The Fas receptor, Fas ligand (FasL) pathway is a major mechanism of apoptosis. Since hematopoietic progenitors can express the Fas receptor, they may be susceptible to apoptosis induced by FasL-expressing cells. We examined FasL expression in the BM of patients with MDS (n = 50), de novo acute myeloid leukemia (AML; n = 10), AML following prior MDS (n = 6), and normal controls (n = 6). Compared to controls, FasL expression was increased in MDS, and was highest in AML. In MDS, FasL expression was seen in myeloid blasts, erythroblasts, maturing myeloid cells, megakaryocytes and dysplastic cells, whereas in AML, intense expression was seen in the blasts. FasL expression correlated with the FAB subtype groups of MDS, and also correlated directly with the percentage of abnormal metaphases on cytogenetic analysis. The FasL expressed in MDS BM inhibited the growth of clonogenic hematopoietic progenitors. This inhibition could be blocked by a soluble recombinant FasFc protein. In MDS, FasL expression in the initial diagnostic BM was higher in patients who were more anemic, correlated directly with red cell transfusion requirements over the subsequent course of the disease, and was predictive of survival. These studies indicate that FasL expression in MDS is of prognostic significance, and suggest that pharmacological blockade of the Fas-FasL pathway may be of clinical benefit.

Acute Disease↗
PubMed1999

Factor(s) secreted by AFT024 fetal liver cells following stimulation with human cytokines are important for human LTC-IC growth.

Soluble factors produced by human marrow stroma or the murine marrow derived M2-10B4 cell line support ex vivo maintenance for 5-8 weeks of 50% of human long-term culture initiating cells (LTC-IC). As the AFT024 cell line supports LTC-IC cultured in contact conditions better than M2-10B4 feeders, we evaluated LTC-IC support in non-contact conditions above AFT024 feeders. We show that only 15% of LTC-IC were maintained for 5 weeks in AFT024 non-contact cultures (n=6, P<0.05). As AFT024-conditioned media added to M2-10B4 non-contact cultures did not inhibit LTC-IC maintenance, AFT024 cells do not secrete factors that inhibit LTC-IC growth. We next characterized heparan sulfate glycosaminoglycans (HS-GAGs) and cytokines produced by AFT024 cells, which are both required for LTC-IC maintenance in M2-10B4 non-contact cultures. The size and extent of O-sulfation of HS-GAGs in AFT024 and M2-10B4 conditioned medium were similar, indicating that absence of hematopoietic specific HS-GAGs is not responsible for the lack of hematopoietic in AFT024 non-contact cultures. Levels of 13 different cytokines secreted in AFT024- and M2-10B4-conditioned medium were similar. However, addition of human SCF, G-CSF, GM-CSF, LIF, MIP-1alpha and IL-6 in concentrations found in human marrow stroma-conditioned medium to AFT024 non-contact cultures increased LTC-IC-maintenance to 72% at 5 weeks. These cytokines improved LTC-IC maintenance in part through interaction with the progenitors and in part, through interaction with the AFT024 feeder. Thus, although LTC-IC maintenance is poor in AFT024 non-contact cultures, addition of human cytokines enhances LTC-IC maintenance in part through indirect effects on the AFT024 feeder. Characterization of known or novel growth factors secreted by AFT024 cells before and after cytokine stimulation may lead to the identification of cytokines that support growth of human hematopoietic stem cells.

Biological Factors↗
PubMed1999

Enterobacter aerogenes outbreak in a neonatal intensive care unit.

BACKGROUND: Enterobacter aerogenes, a Gram-negative bacterium, is an important, although infrequent, cause of nosocomial bacteremia in the hospitalized pediatric and neonatal population. Enterobacter aerogenes was isolated for the first time in our neonatal intensive care unit (NICU) from blood culture of a 5-day-old neonate; 12 more cases were discovered in the next 70 days. The present report summarizes the clinico-bacteriological spectrum and outcome of the affected neonates. Efforts made to find the source of infection and curb the outbreak are also presented. METHODS AND RESULTS: Thirteen newborns, including seven preterms, acquired E. aerogenes septicemia. Perinatal risk factors were present in all the neonates. The mean birthweight of affected infants was 1880 +/- 540 g. Symptoms appeared at a mean age of 3.5 +/- 1.5 days (range 3-8 days). The clinical presentation was indistinguishable from septicemia caused by other Gram-negative organisms. Complications encountered included sclerema, bleeding diathesis, meningitis and shock. The organism, isolated from blood in all and from the cerebrospinal fluid in two cases, was found to be resistant to all antibiotics in the first five cases, but turned sensitive to gentamicin, cefotaxime and amikacin during the latter half of the epidemic. The bacterium in the last case (no. 13) was again found to be resistant to all the antibiotics. Overall mortality was 46.2%; the mean interval between onset of symptoms and death being 2.3 +/- 1.8 days. The organism was traced to the rubber pipe attached to a foot-operated suction machine in the NICU. The neonatal unit was temporarily closed, fumigated and reopened with strict instructions to follow proper hand washing protocol and ensure cohort nursing of infected infants. CONCLUSIONS: Enterobacter aerogenes is capable of causing nosocomial outbreaks of septicemia in NICU. Low birthweight infants with associated perinatal risk factors appear to be predisposed. The sensitivity patterns of the isolates highlight the capability of E. aerogenes to acquire or lose resistance to antibiotics rapidly during treatment. A high mortality rate coupled with a short interval between onset of symptoms and death, suggested high virulence of the strain.

Cross Infection↗
PubMed1999

Effects of anticoagulant, processing delay, and assay method (branched DNA versus reverse transcriptase PCR) on measurement of human immunodeficiency virus type 1 RNA levels in plasma.

We conducted two studies to determine the potential influence of delays in blood processing, type of anticoagulant, and assay method on human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma. The first was an experimental study in which heparin- and EDTA-anticoagulated blood samples were collected from 101 HIV-positive individuals and processed to plasma after delays of 2, 6, and 18 h. HIV-1 RNA levels in each sample were then measured by both branched-DNA (bDNA) and reverse transcriptase PCR (RT-PCR) assays. Compared to samples processed within 2 h, the loss (decay) of HIV-1 RNA in heparinized blood was significant (P < 0.05) but small after 6 h (bDNA assay, -0.12 log(10) copies/ml; RT-PCR, -0.05 log(10) copies/ml) and after 18 h (bDNA assay, -0.27 log(10) copies/ml; RT-PCR, -0.15 log(10) copies/ml). Decay in EDTA-anticoagulated blood was not significant after 6 h (bDNA assay, -0.002 log(10) copies/ml; RT-PCR, -0.02 log(10) copies/ml), but it was after 18 h (bDNA assay, -0.09 log(10) copies/ml; RT-PCR, -0.09 log(10) copies/ml). Only 4% of samples processed after 6 h lost more than 50% (>/=0.3 log(10) copies/ml) of the HIV-1 RNA, regardless of the anticoagulant or the assay that was used. The second study compared HIV-1 RNA levels in samples from the Multicenter AIDS Cohort Study (MACS; samples were collected in heparin-containing tubes in 1985, had a 6-h average processing delay, and were assayed by bDNA assay) and the British Columbia Drug Treatment Program (BCDTP) (collected in EDTA- or acid citrate dextrose-containing tubes in 1996 and 1997, had a 2-h maximum processing delay, and were assayed by RT-PCR). HIV-1 RNA levels in samples from the two cohorts were not significantly different after adjusting for CD4(+)-cell count and converting bDNA assay values to those corresponding to the RT-PCR results. In summary, the decay of HIV-1 RNA measured in heparinized blood after 6 h was small (-0.05 to -0.12 log(10) copies/ml), and the minor impact of this decay on HIV-1 RNA concentrations in archived plasma samples of the MACS was confirmed by the similarity of CD4(+)-cell counts and assay-adjusted HIV-1 RNA concentrations in the MACS and BCDTP.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection.

To understand the high variability of the asymptomatic interval between primary human immunodeficiency virus type 1 (HIV-1) infection and the development of AIDS, we studied the evolution of the C2-V5 region of the HIV-1 env gene and of T-cell subsets in nine men with a moderate or slow rate of disease progression. They were monitored from the time of seroconversion for a period of 6 to 12 years until the development of advanced disease in seven men. Based on the analysis of viral divergence from the founder strain, viral population diversity within sequential time points, and the outgrowth of viruses capable of utilizing the CXCR4 receptor (X4 viruses), the existence of three distinct phases within the asymptomatic interval is suggested: an early phase of variable duration during which linear increases ( approximately 1% per year) in both divergence and diversity were observed; an intermediate phase lasting an average of 1.8 years, characterized by a continued increase in divergence but with stabilization or decline in diversity; and a late phase characterized by a slowdown or stabilization of divergence and continued stability or decline in diversity. X4 variants emerged around the time of the early- to intermediate-phase transition and then achieved peak representation and began a decline around the transition between the intermediate and late phases. The late-phase transition was also associated with failure of T-cell homeostasis (defined by a downward inflection in CD3(+) T cells) and decline of CD4(+) T cells to </=200 cells/microliter. The strength of these temporal associations between viral divergence and diversity, viral coreceptor specificity, and T-cell homeostasis and subset composition supports the concept that the phases described represent a consistent pattern of viral evolution during the course of HIV-1 infection in moderate progressors. Recognition of this pattern may help explain previous conflicting data on the relationship between viral evolution and disease progression and may provide a useful framework for evaluating immune damage and recovery in untreated and treated HIV-1 infections.

Base Sequence↗
PubMed1999

Systemic brucellosis with chronic meningitis: A case report.

A young adult presenting with 11 months history of fever, headache, vomiting was found to have CSF lymphocytic pleocytosis with increased protein. His serum tested strongly positive for Brucella (standard tube agglutination titre 1: 320) whereas CSF was weakly positive. He became asymptomatic on treatment with tetracycline, rifampicin and streptomycin with significant CSF response. This case is reported because of its rarity.

Adult↗
PubMed1999

Brainstem auditory evoked potentials among rubber factory workers.

The study was conducted on 27 rubber factory workers for the functional assessment of brainstem auditory pathway. Neurobehavioural questionnaire was administered to the workers and the personal sampler was used to evaluate the respirable particulate load inhaled per day of each worker along with qualitative analysis for PAH compounds. Evoked potential recording was carried out for brainstem auditory responses. Chest X-rays of workers exhibited varied abnormal features. Multiple regression analysis of data showed definite prolongation of latencies with increasing concentration of respirable particulate load though it was not statistically significant. Comparison with normative data indicated prolongation of latencies of rubber factory workers.

Adult↗
PubMed1999

Ventilatory functions in stone quarry workers of Rajasthan.

Ninety two stone quarry workers from nearby villages of Jodhpur town were, assessed for their lung functions which included measurement of Forced vital capacity (FVC), Forced expiratory volume in Ist second (FEV1), and Peak expiratory flow rate (PEFR). A detailed questionnaire was administered to all the workers, who were divided into group I (cutting the stone) and group II (loading and unloading the stone) depending on the nature of their Job. The presenting complaints included cough with sputum (55%), chest pain (79%), bodyache (31%) and 21% gave the history as suffering from tuberculosis. Comparison of the lung function results between two groups indicated a significant decrement of FEV1 and PEFR in group II as compared to group I workers. The observed lung functions were also found to be lower on comparison with the normative data from Rajasthan. However, no difference in observed lung function results of smokers and nonsmokers were obtained. Thus the reported lower values of lung functions independent of smoking habits, may be due to occupational stone dust exposure.

Adult↗
PubMed1999

Inverted mesiodens--a case report.

A nine and a half years old female school child was examined in a during routine dental examination. The patient had swelling over maxillary midline area just near the labial frenum. Both the central incisors were in position. Radiographic examination revealed presence of an inverted supernumerary tooth between the roots of the central incisors. Surgical extraction of the supernumerary was planned. A unique case of inverted (upside down) mesiodens is presented.

Child↗
PubMed1999

Impact of a multi-method promotional package on awareness and knowledge about STD and AIDS among the trainees of an industrial training institute in a resettlement colony of Delhi, India.

To design and apply a multi-method promotional package for enhancing awareness and knowledge on STD and AIDS among ITI trainees, and evaluate its impact, an intervention study, using pre and post assessment of the subjects for comparison was carried out. The study was carried out in the Industrial Training Institute (ITI), in a resettlement colony of Delhi. Urethral/vaginal discharge, genital ulcer and pain on micturition were identified as symptoms of STD by a significantly higher number of respondents in the post package sample. A sizable number of subjects included inguinal swelling and lower abdominal pain also as STD symptoms. The IEC intervention showed a significant improvement in knowledge about all four major routes of transmission of HIV/AIDS. Using condoms and avoiding sex with Commercial Sex Workers were reported as measures to prevent STD/AIDS by a significantly higher number of subjects after the intervention. A sizable number of subjects also included other measures (using safe blood/not sharing needles etc.) as well. There was a significant decline in the subjects preferring self treatment or treatment from a chemist shop in case one suffered with an STD. A significant increase was observed in those preferring treatment from govt. facilities or private allopathic doctors. However, the intervention did not seem to result in preference for alternative systems of medicine. The study demonstrated that exposure to intensive promotional intervention, even for a brief period can significantly raise awareness and knowledge of young people even on sensitive topics like STD and AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Structurally specific heparan sulfates support primitive human hematopoiesis by formation of a multimolecular stem cell niche.

Stem cell localization, conservation, and differentiation is believed to occur in niches in the marrow stromal microenvironment. Our recent observation that long-term in vitro human hematopoiesis requires a stromal heparan sulfate proteoglycan (HSPG) led us to hypothesize that such HSPG may orchestrate the formation of the stem cell niche. We compared the structure and function of HS from M2-10B4, a hematopoiesis-supportive cell line, with HS from a nonsupportive cell line, FHS-173-We. Long-term culture-initiating cell (LTC-IC) maintenance was enhanced by PG from supportive cells but not by PG from nonsupportive cells (P <.005). The supportive HS were significantly larger and more highly sulfated than the nonsupportive HS. Specifically, supportive HS contained higher 6-O-sulfation on the glucosamine residues. In agreement with these observations, purified 6-O-sulfated heparin and highly 6-O-sulfated bovine kidney HS similarly maintained LTC-IC. In contrast, completely desulfated heparin, N-sulfated heparin, and unmodified heparin did not support LTC-IC maintenance. Moreover, the supportive HS promoted LTC-IC maintenance but not differentiation of CD34(+)/HLA-DR- cells into colony-forming cells (CFCs) and mature blood cells. The supportive HS but not the nonsupportive HS bound both cytokines and matrix components critical for hematopoiesis, including interleukin-3 (IL-3), macrophage inflammatory protein-1 (MIP-1), and thrombospondin (TSP). Significantly more CD34(+) cells adhered directly to immobilized O-sulfated heparin than to N-sulfated or desulfated heparin. Thus, hematopoiesis-supportive stromal HSPG possessing large, highly 6-O-sulfated HS mediate the juxtaposition of hematopoietic progenitors with stromal cells, specific growth-promoting (IL-3) and growth-inhibitory (MIP-1 and platelet factor 4 [PF4]) cytokines, and extracellular matrix (ECM) proteins such as TSP. We conclude that the structural specificity of stromal HSPG that determines the selective colocalization of cytokines and ECM components leads to the formation of discrete niches, thereby orchestrating the controlled growth and differentiation of stem cells. These findings may have important implications for ex vivo expansion of and gene transfer into primitive hematopoietic progenitors.

Antigens, CD34↗
PubMed1998

Anti-HIV type 1 memory cytotoxic T lymphocyte responses associated with changes in CD4+ T cell numbers in progression of HIV type 1 infection.

We investigated memory cytotoxic T lymphocyte (CTLm) responses to HIV-1 as a determinant of HIV-1 disease progression, in relation to plasma HIV-1 load and T lymphocyte numbers in a longitudinal study of 14 homosexual men with incident HIV-1 infection. Study participants were selected who exhibited failure of T cell homeostasis, i.e., a downward inflection in CD3+ T cells that occurs in >75% of persons 1.5 to 2.5 years before development of AIDS, and compared with participants who developed low CD4+ T cell counts associated with possible T cell homeostasis failure, a subject who progressed rapidly to AIDS without well-defined T cell inflection, and subjects who had long-term preservation of T cell homeostasis (nonprogressors). High CTLm responses against Gag, but not Pol or Env, soon after seroconversion were associated with a slower loss of CD4+ T cells 1-4 years after seroconversion. Anti-Env CTLm responses decreased in most subjects around the time that T cell homeostasis failed. Plasma HIV-1 RNA increased exponentially (1.59-fold per year) over the 5 years preceding failure of T cell homeostasis, and there was a shift from a non-syncytium-inducing/CCR5 coreceptor phenotype of HIV-1 to a syncytium-inducing/CXCR4 phenotype, regardless of high or increasing levels of anti-HIV-1 CTLm during this time. These observations suggest that decreases in CTLm and increasing virus load are independent factors contributing to HIV-1 disease progression.

CD4 Lymphocyte Count↗
PubMed1998

Re-expression of p16INK4a in mesothelioma cells results in cell cycle arrest, cell death, tumor suppression and tumor regression.

Absence of expression of the p16IKN4a gene product is commonly observed in mesothelioma tumors and cell lines, while wild-type pRB expression is maintained. We have examined the biologic and potential therapeutic role of re-expressing p16INK4a gene product in mesothelioma cells and tumors. Following transduction with a p16INK4a expressing adenovirus (Adp16), over-expression of p16INK4a in mesothelioma cells resulted in cell cycle arrest, inhibition of pRB phosphorylation, diminished cell growth, and eventual death of the transduced cells. Expression of p16INK4a protein was accompanied by decreased expression of pRB as detected by immunoblot and immunohistochemistry. Experiments in mesothelioma xenografts demonstrated inhibition of tumor formation, tumor growth arrest and diminished tumor size and spread. p16INK4a gene product expression was also demonstrated in intraperitoneal xenografts of human mesothelioma cells. These results demonstrate that p16INK4a gene transfer may play a therapeutic role in the treatment of mesothelioma.

Animals↗
PubMed1998

The lordotic effect of the OSI frame on operative adolescent idiopathic scoliosis patients.

STUDY DESIGN: A prospective evaluation of adolescent idiopathic scoliosis patients undergoing operative treatment on the Orthopedic Systems Incorporated (OSI; Jackson) frame. OBJECTIVES: To investigate prospectively thoracic, thoracolumbar, and lumbar sagittal alignments in patients with adolescent idiopathic scoliosis who undergo an instrumented posterior spinal fusion on the OSI frame. SUMMARY OF BACKGROUND DATA: In several studies, it has been shown that patient positioning on various operative frames is an important component of ultimate lumbar sagittal alignment. However, these studies have all concentrated on the lumbar spine, and no sagittal plane alignment data in adolescent idiopathic scoliosis patients have been reported in the thoracic and thoracolumbar junction as it relates to intraoperative positioning, correction maneuvers and correlative postoperative results. METHODS: Thirty-nine patients with operative adolescent idiopathic scoliosis treated with an instrumented posterior spinal fusion on the OSI frame were prospectively evaluated. Standing preoperative, intraoperative, and postoperative long-cassette lateral radiographs were reviewed with regional and segmental Cobb measurements of the thoracic, thoracolumbar junction, and lumbar spine obtained. RESULTS: Thoracic kyphosis (T1-T12) measured +34 degrees before surgery, +28 degrees during surgery, and +30 degrees after surgery, Thus, a statistically significant decrease was noted in thoracic kyphosis secondary to prone positioning on the OSI frame ( P < 0.05). Thoracolumbar spine measurements from T10 to L2 also showed a lordotic trend from +2 degrees before surgery, to -4 degrees during surgery, to -8 degrees after surgery, which was also statistically significant (P < 0.05). Total lumbar lordosis from T12 to S1 remained relatively unchanged from -60 degrees before surgery, to -59 degrees during surgery, to -60 degrees after surgery. However, segmental lumbar lordosis measured from T12 to the lowest instrumented vertebra showed a statistically significant increase in lordosis from -17 degrees before surgery, to -19 degrees during surgery, to -23 degrees after surgery (P < 0.05). Those patients in whom lumbar pedicle screws were used (vs. hooks alone) had the greatest increase in lumbar instrumented lordosis. CONCLUSIONS: Performing adolescent idiopathic scoliosis correction on the OSI frame tends to decrease thoracic kyphosis, increase thoracolumbar lordosis, and increase segmental instrumented lumbar lordosis, while it maintains total lumbar lordosis.

Adolescent↗