Search PubMed⌕ Search

Biomedical subjects

P Gupta

Publications and source records attributed to P Gupta.

At least 19 recordsLinked to original sources
PubMed2000

Dependence of CD8+ T-cell-mediated suppression of HIV type 1 on viral phenotypes and mediation of phenotype-dependent suppression by viral envelope gene and not by beta-chemokines.

CD8+ T-cell-mediated HIV-1 suppressive activity has been shown against a number of strains of HIV-1 and HIV-2. In this study using a semiquantitative assay, we showed that CD8+ T cells from seropositive subjects and herpes virus saimiri transformed CD8+ T-cell clones from HIV-1-infected subjects exhibited 5 to 100-fold higher suppressive activity against slow replicating nonsyncytia-inducing strains (Slow/NSI) as compared to fast replicating syncytia-inducing strains (Fast/SI) of HIV-1. Such differential suppressive activity was not due to beta-chemokines as evidenced by the lack of blocking activity of antibodies to RANTES, MIP-1beta, and MIP-1alpha on the antiviral activities of CD8+ T cells. Moreover, there was no correlation between the level of CD8+ T-cell suppression and the level of these beta-chemokines in culture supernatant. Results from the CD8+ T-cell-mediated suppressive activity against two molecular cloned virus ME1 (Slow/NSI), ME46 (Fast/SI), and their interstrain recombinants indicate that the envelope gene carries a major genetic determinant responsible for this phenotypic-dependent differential suppressive activity.

CD4-Positive T-Lymphocytes↗
PubMed2000

Human LTC-IC can be maintained for at least 5 weeks in vitro when interleukin-3 and a single chemokine are combined with O-sulfated heparan sulfates: requirement for optimal binding interactions of heparan sulfate with early-acting cytokines and matrix proteins.

We have shown that stromal O-sulfated heparan sulfate glycosaminoglycans (O-S-GAGs) regulate primitive human hematopoietic progenitor cell (HPC) growth and differentiation by colocalizing heparin-binding cytokines and matrix proteins with HPC in stem cell "niches" in the marrow microenvironment. We now show that long-term culture-initiating cells (LTC-IC) are maintained for 5 weeks in the absence of stroma when O-S-GAGs are added to IL-3 and either MIP-1alpha or PF4 (LTC-IC maintenance without GAGs, 32 +/- 2%; with GAGs, 95 +/- 7%; P <.001). When cultured with 5 additional cytokines, O-S-GAGs, IL-3, and MIP-1alpha, LTC-IC expanded 2- to 4-fold at 2 weeks, and 92 +/- 8% LTC-IC were maintained at 5 weeks. Similar results were seen when PF4 replaced MIP-1alpha. Although O-S-GAG omission did not affect 2-week expansion, only 20% LTC-IC were maintained for 5 weeks. When O-S-heparin was replaced by completely desulfated-, N-sulfated (O-desulfated), or unmodified heparins, LTC-IC maintenance at week 5 was not better than with cytokines alone. Unmodified- and O-S-heparin, but not desulfated- or N-sulfated heparin, bound to MIP-1alpha, IL-3, PF4, VEGF, thrombospondin, and fibronectin. However, the affinity of heparin for thrombospondin and PF4, and the association and dissociation rates of heparin for PF4, were higher than those of O-S-heparin. We conclude that (i) although cytokines may suffice to induce early expansion, adult human LTC-IC maintenance for longer than 1 month requires O-S-GAGs, and (ii) HPC support may depend not only on the ability of GAGs to bind proteins, but also on optimal affinity and kinetics of interactions that affect presentation of proteins in a biologically active manner to progenitors. (Blood. 2000;95:147-155)

Adult↗
PubMed2000

Diagnostic value of lymph node fine needle aspiration cytology: an institutional experience of 387 cases observed over a 5-year period.

Lymph node fine needle aspiration (LNFNA) cytology is valuable in solving the diagnostic problems of clinical adenopathy. The usefulness of the procedure in the staging and diagnosis of various malignant and lymphoproliferative tumours, as well as its role in distinguishing reactive hyperplastic lymph nodes from lymphoma, has been documented in the literature generally on an individual basis. We report our cumulative 5 year experience of LNFNA representing 387 cases. Approximately half (n = 182) were diagnosed as either metastatic carcinoma or melanoma; in 54 cases (30%) excisional biopsy or tissue study was performed to confirm the diagnosis; there was only one false-positive diagnosis of a metastatic squamous carcinoma rendered on a submandibular lymph node. Sixty-one lymphoma cases were successfully diagnosed via LNFNA with no false positives; concurrent flow cytometry was utilized in 51% (n = 31) of the 61 cases and supported the cytologic diagnosis of lymphoma in 27 of the 31 cases (87%). A benign or reactive lymph node process was also diagnosed via LNFNA alone or in combination with flow cytometry in 48 cases with only five false negatives, which included four cases of mantle cell lymphoma and one case of melanoma. Unsatisfactory cases accounted for 12%, and represented specimens obtained by 'Wang needle' or other emerging techniques. Our study demonstrates that LNFNA can be an accurate, economical and rapid diagnostic procedure.

Adult↗
PubMed2000

Hydatiduria.

Explore the source record for details and available documents.

Child↗
PubMed1999

The quantification of low back disorder using motion measures. Methodology and validation.

STUDY DESIGN: Trunk angular motion features were used as a means to quantify the extent of a low back disorder in healthy people and patients with chronic low back disorders. OBJECTIVE: To refine and validate a previously reported means of quantifying the extent of a low back disorder. SUMMARY AND BACKGROUND: Many assessment tools of low back disorder are subjective. A quantitative assessment tool would facilitate the tracking of the recovery and help document the appropriateness of treatments. METHODS: The trunk motion characteristics of 374 healthy people and 335 patients with chronic low back disorders of varying severity were documented as they flexed and extended their trunks in five different planes of motion. The trunk motion features were normalized as a function of age and gender. Four classification techniques were used to assess the ability of the quantitative motion measure to identify those with and without low back disorders. In addition, 31 patients were observed longitudinally to determine whether the motion measures agreed with observed changes in back pain symptoms. RESULTS: The quantitative trunk motion measure distinguished between people with low back disorders and healthy people between 88% and 94% of the time, depending on which classification system was used. Sensitivity and specificity varied between 83% and 97%. The quantitative measure also showed promise as a means to distinguish between muscle-based and structure-based low back disorders. Prospective findings indicated that the quantification system agreed well with clinical observations of progress. CONCLUSIONS: The quantification of trunk motion can serve as a measure of the extent of a low back disorder. When considered along with other clinical information, the ability to assess and treat low back disorders is enhanced.

Adult↗
PubMed1999

VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling.

Vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, promotes endothelial cell survival and angiogenesis. We recently showed that VEGF can support the growth of human dermal microvascular endothelial cells (HDMEC) and human umbilical vein endothelial cells in serum-free medium. Reasoning that VEGF might be modulating apoptotic signal transduction pathways, we examined mechanisms involved in the anti-apoptotic effect of VEGF on starvation- and ceramide-induced apoptosis in HDMEC. We observed that VEGF ameliorated the time-dependent increase in apoptosis, as demonstrated by morphologic observations, TUNEL assay, and DNA fragmentation. On the other hand, basic fibroblast growth factor only partially prevented apoptosis in serum-starved HDMEC; platelet-derived growth factor-BB was completely ineffective. VEGF activated the phosphorylation of extracellular signal regulated kinase (ERK)1 (p44 mitogen-activated protein kinase; MAPK) and ERK2 (p42 MAPK) in a time- and concentration-dependent manner. Both the VEGF-induced activation and its anti-apoptotic effect were prevented by the specific MAPK/ERK inhibitor PD98059. The presence of VEGF also inhibited the sustained activation of stress-activated protein kinase/c-jun-NH2-kinase (SAPK/JNK) caused by serum starvation and ceramide treatment. Activation of the MAPK pathway together with inhibition of SAPK/JNK activity by VEGF appears to be a key event in determining whether an endothelial cell survives or undergoes programmed cell death.

Apoptosis↗
PubMed1999

Cervical dysplasia on cervicovaginal Papanicolaou smear among HIV-1-infected pregnant and nonpregnant women. Women and Infants Transmission Study.

OBJECTIVE: To assess the association of squamous intraepithelial lesions (SIL) on cervicovaginal Papanicolaou (Pap) smear among women infected with HIV-1 and their pregnancy status, and historical and clinical factors. METHODS: Study enrollment Pap smears of 452 pregnant and 126 nonpregnant HIV-infected women had cytologic evaluation. The rates of SIL were compared with pregnancy status, immunosuppression, presence of sexually transmitted diseases (STDs) and demographic features. RESULTS: Rates of low grade SIL were similar for pregnant and nonpregnant HIV-1-infected women (17% and 23.8%, respectively; p = .09). Of them, 12 women, 9 pregnant and 3 nonpregnant, had high grade SIL. None had invasive cervical cancer. Low CD4 percentage (odds ratio, [OR] = 3.8; 95% confidence interval [CI], 2.0-7.3) and inflammation (OR = 2.8; 95% CI, 1.8-4.3) were associated with SIL. An association between herpes simplex and SIL (OR = 3.3; 95% CI, 1.1-9.5) was less certain due to clinical diagnosis and low prevalence of herpes simplex (17 of 456 women). CONCLUSIONS: Pap smears for a cohort of HIV-infected pregnant and nonpregnant women revealed a high prevalence of LGSIL but a low prevalence of HGSIL and no cases of cervical cancer. Although pregnancy may not affect the rate of Pap smear abnormalities, SIL is associated with immunosuppression, cervical inflammation, and herpes simplex. Closer surveillance of HIV-1-infected women with these risk factors may be warranted.

Adolescent↗
PubMed1999

Characterisation of the contractile activity of eletriptan at the canine vascular 5-HT1B receptor.

The functional activity of eletriptan ((R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]- 1 H-indole) at the contractile serotonin (5-hydroxytryptamine; 5-HT) '1B-like' receptor in dog isolated saphenous vein and basilar artery was investigated. Eletriptan, like 5-HT and sumatriptan potently contracted saphenous vein (pEC50: 6.3, 6.9 and 6.1, respectively) and basilar artery (pEC50 7.2, 7.5 and 6.8, respectively). The maximum responses evoked by eletriptan was, unlike sumatriptan, significantly lower than that to 5-HT (intrinsic activity saphenous vein: eletriptan 0.57, 5-HT 1.0, sumatriptan 0.85; basilar artery: eletriptan 0.77, 5-HT 0.98, sumatriptan 0.89). Contractions evoked by eletriptan were antagonised by the 5-HT1B/1D receptor antagonist GR125743 (N-[4-methoxy-3-(4-methyl piperazin-1-yl)phenyl]-3-methyl-4-(4-pyridyl)benzamide) with pA2 values of 9.1 in saphenous vein and 9.4 in basilar artery. Affinity estimates (pKA) for 5-HT and sumatriptan determined from receptor alkylation studies in saphenous vein were 6.6 and 6.3, respectively, compared to the apparent equilibrium dissociation constant (pKp) for eletriptan of 6.8. The rank order of relative intrinsic efficacies (epsilon) was 5-HT > sumatriptan > eletriptan. Thus, eletriptan required greater receptor occupancy (4.4-fold) to evoke an equivalent contraction to 5-HT and sumatriptan in dog isolated saphenous vein. These data demonstrate that eletriptan is a potent partial agonist at the canine vascular 5-HT1B receptor.

Alkylation↗
PubMed1999

Mechanism of interaction of thrombospondin with human endothelium and inhibition of sickle erythrocyte adhesion to human endothelial cells by heparin.

Thrombospondin (TSP) mediates sickle erythrocyte adhesion to endothelium, but the mechanism remains unknown. Since TSP is comprised of heterogeneously distinct domains, this adhesion may depend on the interaction of specific regions of TSP with different cell surface receptors. To examine the mechanisms of interaction of TSP with human umbilical vein endothelial cells (HUVEC), we performed binding studies using soluble [125I]TSP. Our data showed that (i) monoclonal antibodies (MoAbs) against cell surface heparan sulfate (HS) or the heparin-binding domain of TSP, or cleavage of HS on HUVEC by heparitinase reduced TSP binding by 28-40%, (ii) the RGD peptide or MoAbs against integrin alpha v beta 3 or the calcium binding region of TSP inhibited binding by 18-28%, and (iii) a MoAb against the cell-binding domain of TSP inhibited binding by 36%. Unmodified heparin inhibited the binding of TSP to endothelial cells by 70% and did so far more effectively than selectively desulfated heparins, HS or chondroitin sulfate. Heparin inhibited TSP binding to HUVEC at much lower concentrations than were required to inhibit TSP binding to sickle erythrocytes. Unmodified heparin effectively inhibited the TSP-mediated adhesion of sickle erythrocytes to HUVEC. These data imply that cell surface HS-mediated mechanisms play a key role in TSP-mediated sickle erythrocyte adhesion to endothelium, and heparin may be of use for inhibition of this adhesion.

Anemia, Sickle Cell↗
PubMed1999

Expression and purification of the recombinant protective antigen of Bacillus anthracis.

Protective antigen (PA) is a major component of the vaccine against anthrax. The structural gene for the 83-kDa PA was expressed as fusion protein with 6x Histidine residues in Escherichia coli. Expression of PA in E. coli under the transcriptional regulation of the T5 promoter yielded an insoluble protein aggregating to form inclusion bodies. The inclusion bodies were solubilized in 6 M guanidine-HCl and the protein was purified under denaturing conditions using nickel nitrilotriacetic acid (Ni-NTA) affinity chromatography. The denatured protein was renatured by gradual removal of the denaturant while immobilized on the Ni-NTA column. The protein was then purified using Mono-Q column on FPLC. The yield of the purified recombinant PA (rPA) from this procedure was 2 mg/liter of the culture. The rPA had an apparent molecular mass of 83 kDa as determined by SDS-PAGE. Antisera to native PA recognized the fusion protein. The rPA was biologically as well as functionally active. Thus, the recombinant PA may be used to develop an effective recombinant vaccine against anthrax.

Animals↗
PubMed1999

Long-term blood product transfusion support for patients with myelodysplastic syndromes (MDS): cost analysis and complications.

Patients with myelodysplastic syndromes (MDS) frequently become dependent on blood transfusions. We analyzed the total transfusion support required, and its complications and cost, following the diagnosis of MDS (total period = 79.7 patient-years) in 50 patients followed at the Minneapolis VA Medical Center. From diagnosis of MDS to transformation to AML or death (the MDS phase), 41 patients (82%) required transfusions. The median numbers of transfused blood products per patient per year of follow-up in the MDS phase were: packed red blood cells (pRBC), 11.1 (range, 0-91.3) units, random donor platelets (RDP), 6.8 (range, 0-581) units, and single donor apheresis platelet packs (SDP): 0 (range, 0-40) collections. In the AML phase (time from diagnosis of secondary AML to death or last follow-up), median transfusion requirements per patient (n = 5) were 24 (range, 8-88) units pRBC, 94 (range, 24-480) units RDP and 3 (range, 0-19) collections of SDP. Overall, 80% of patients required either special processing or selection of blood products, had reactions to blood products or required premedications (specified/complicated transfusions); 94% of all pRBC and 97% of all platelet transfusions were specified/complicated. The median cost of transfusions per patient was $4048 (range, $0-73210) during the MDS phase and $13210 (range, $5288-59010) during the AML phase. During the MDS phase, the median cost was $4877 (range, $0-67050) per patient-year of follow-up; the major proportion of this cost was for pRBC transfusions. Long-term support with frequent transfusions for MDS usually requires specially selected or processed blood products, and is associated with a high incidence of transfusion reactions. This study provides baseline data on the costs of transfusion support for MDS, and can be used for comparing resource utilization and costs of long-term transfusion support (supportive care) with growth factor therapy or disease-modifying modalities such as allogeneic transplantation.

Blood Transfusion↗
PubMed1999

Cadmium induced thyroid dysfunction in chicken: hepatic type I iodothyronine 5'-monodeiodinase activity and role of lipid peroxidation.

Administration of cadmium chloride (2.5 mg/kg body weight/day) to chickens daily for 15 days decreased serum triiodothyronine (T3) concentration (by 68.75%) without altering the levels of serum thyroxine (T4). Hepatic 5'-monodeiodinase (5'D-I) and superoxide dismutase (SOD) activities were also decreased (by 90.47% and 20.81% respectively) with a concomitant increase in lipid peroxidation (LPO, by 206.25%). Administration of the antioxidant vitamin E (alpha-tocopherol, 5 mg/kg body weight on alternate days) to cadmium intoxicated chickens restored thyroid function by maintaining normal hepatic 5'D-I activity and serum thyroid hormone concentrations. It also prevented cadmium-induced increase in LPO. We conclude that the metal-induced inhibition in hepatic 5'D-I activity is mediated through LPO.

Animals↗
PubMed1999

Activation of phospholipase C and protein kinase C is required for expression of anthrax lethal toxin cytotoxicity in J774A.1 cells.

Anthrax lethal toxin (LT) comprises two proteins: the protective antigen (PA) and the lethal factor (LF). The LT is cytotoxic to macrophage-like cell line J774A.1. Pre-treatment of these cells with neomycin, a phospholipase C inhibitor, protected them against anthrax LT cytotoxicity. Protection obtained with neomycin indicated that LT stimulates phospholipase C in these cells. It was found that levels of inositol 1,4,5-triphosphate (IP3) dramatically increased in toxin-treated cells. The rise in IP3 levels was proportional to the dose of LF that was allowed to bind to receptor-bound PA. By using protein kinase C (PKC) inhibitors, we found that the activation of PKC is required for mediating anthrax LT cytotoxicity. Activation of phospholipase C or PKC is not required for the binding of PA to the cell surface receptors or for the uptake or internalisation of the toxin. In this study, we demonstrate that the IP3 signalling cascade is initiated by anthrax lethal toxin in J774A.1 cells. The second messengers generated during the cascade aid LF in mediating lethality only after its translocation into the cytosol.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
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↗