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Biomedical subjects

M K Gupta

Publications and source records attributed to M K Gupta.

At least 37 records · Page 2Linked to original sources
PubMed1997

Combined nested reverse transcription-PCR assay for prostate-specific antigen and prostate-specific membrane antigen in detecting circulating prostatic cells.

Accurate staging is an important issue in managing patients with prostate cancer. Current staging modalities are poor predictors for locally advanced disease. In the present study, we investigated the role of a peripheral blood-based, nested reverse transcription-PCR (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) in prostate cancer staging. Our nested RT-PCR could detect both PSA and PSM mRNA in one LNCaP cell diluted in 10(6) mononuclear cells. None of the controls, including patients with benign prostate hyperplasia, normal male subjects, and female subjects, were positive for either marker, confirming the assay's specificity for prostate cancer. In patients with bony metastases, 100% were positive by combined PSA/PSM assays (64% by PSA and 91% by PSM). In patients with clinically localized prostate cancer, 29% were positive by combined PSA/PSM assays (13% by PSA and 23% by PSM). The combined PSA/PSM assay is more sensitive than the PSA assay alone in detecting circulating prostatic cells (P = 0.0071). PSM is a more sensitive marker than PSA (P = 0.042). We also correlated preoperative nested RT-PCR results with pathological findings in prostatectomy patients. Nested RT-PCR for PSA/PSM has an odds ratio of 20 in predicting tumor extracapsular penetration (P = 0.017). These results indicate that a nested RT-PCR result may provide the staging information unavailable from other modalities, including the clinical stage, initial serum PSA, and Gleason score. Additional investigation is needed to determine the ultimate role of this assay in the management of patients with prostate cancer.

Antigens, Neoplasm↗
PubMed1996

Immunoradiometric assay measurements of insulin-like growth factor-I (IGF-I): comparison with radioimmunoassays using native or des (1-3) IGF-I as radioligands.

Insulin-like growth-factor-binding proteins (BPs) in serum interfere with the measurement of insulin-like growth factor-I (IGF-I). Various assays have been developed to overcome this interference. We evaluated an immunoradiometric (IRMA) assay and compared it with the radioimmunoassay (RIA) using both native IGF-I and a truncated form of IGF-I [des (1-3) IGF-I] as radioligands. The IRMA was simpler (one step assay) and faster (3 hr incubation) than RIA(s) (overnight incubation). Sera were extracted with acid ethanol (AE) before all three assays. Analysis of serum samples (n = 78) performed by use of the two different radioligands in the RIA assays were highly correlated (r = 0.967, P < 0.0001). Measurements of serum IGF-I by IRMA in same samples were also highly correlated with those of the RIA assays (r = 0.952 for RIA and 0.947 for triGF-I RIA, P < 0.0001 for both). To assess the effect of binding protein-3 (BP-3) levels (after AE extraction) on these assays, BP-3 levels were measured in sera from 36 healthy women. The mean BP-3 level was 3.6 +/- 0.79 (S.D.) mg/L (range 1.3-5.0), and there was no significant difference in IGF-I levels measured by the three assays. Also, BP-3 levels were inversely correlated with IGF-I levels as measured by all three methods (r = 0.73 for IRMA, 0.71 for triGF-I, and 0.75 for IGF-I RIA). To assess the effect of binding protein-1 (BP-1) levels on these assays, IGF-I was also measured by IRMA and trlGF-I RIA in 19 women with advanced breast cancer. Women with breast cancer had significantly higher (P < 0.001) BP-1 levels than age matched healthy women. IGF-I levels measured by IGF-I IRMA were slightly lower than those measured by trlGF-I RIA in breast cancer patients. However, this difference was not statistically significant (P = 0.56). These findings suggest that variations in BP-3 or BP-1 levels after AE extraction have no significant effect in any of these assays. "We conclude that trlGF-I as a radioligand provides no added advantage over the standard IGF-I RIA. We also conclude that the IRMA assay is valid for measuring IGF-I and is faster and more convenient than RIA.

Adult↗
PubMed1996

Expression of interleukin-6 in osteoarthritic chondrocytes and effects of fluid-induced shear on this expression in normal human chondrocytes in vitro.

This study tested the effect of fluid-induced shear on interleukin-6 expression in normal human articular chondrocytes in vitro. As determined by Northern blot analysis, interleukin-6 mRNA expression occurs in chondrocytes from osteoarthritic cartilage but not in normal chondrocytes. Applying fluid-induced shear stress to primary high density cultures of chondrocytes increased interleukin-6 mRNA signal 4-fold at 1 hour and 10 to 15-fold at 48 hours compared with unsheared control cultures. At 48 hours, fluid-induced shear stress increased interleukin-6 protein levels in the culture medium 9 to 10-fold compared with unsheared controls. mRNA signals for interleukin-1alpha, interleukin-1beta, and tumor necrosis factor-alpha in RNA from sheared or control chondrocytes were not detected by Northern blotting. Transforming growth factor-beta mRNA signal was detectable but was not affected by shear. In contrast, human lung fibroblasts (WI-38) responded to fluid-induced shear with increased signal for transforming growth factor-beta, but not interleukin-6, mRNA. Both cell types did respond to interleukin-1alpha with increased interleukin-6 mRNA signal. These data demonstrated that distortional forces, such as fluid-induced shear stress, alter interleukin-6 levels in normal chondrocytes in vitro and suggest that increased interleukin-6 expression in osteoarthritic cartilage may result, in part, from alterations in the mechanical loading of the tissue.

Adult↗
PubMed1996

Effect of cranial surgery and brain tumor size on emergence from anesthesia.

BACKGROUND: Knowing which neurosurgical patients are at risk for delayed awakening may lead to better utilization of intensive care resources and avoid the risk and cost of pharmacologic reversal and diagnostic tests. METHODS: The authors compared anesthetic emergence from complex spinal surgery (spine; n = 47) with that from craniotomy for supratentorial nonfrontal (n = 22), frontal (n = 34), or posterior fossa tumor (n = 28). A further comparison involved patients with small versus large (diameter > 30 mm, mass effect) tumors. The standardized anesthetic regimen consisted of induction with 2-4 mg/kg-1 thiopental and 1-2 micrograms/kg-1 sufentanil, followed by maintenance with nitrous oxide, 0.2-0.5 micrograms.kg-1.h-1 sufentanil and < or = 0.5% isoflurane. Sufentanil administration was terminated on dural or spinal muscle closure, isoflurane during skin closure, and nitrous oxide during dressing application. After discontinuing nitrous oxide, a minineurologic examination was performed every 15 min for 1 h, then hourly for 4 h and at 24 h. RESULTS: Craniotomy patients performed less well than spinal surgery patients on the minineurologic examination 15 and 30 min after discontinuing nitrous oxide. At 15 min, fewer patients with large (vs. small) tumors were oriented to time (58% vs. 87%; P < 0.01) or place (67% vs. 90%; P < 0.01). Forty-two percent of patients with large tumors still had an abnormal minineurologic examination score versus 15% of patients with small tumors. At 30 min, these values were 28% and 8%, respectively (P < 0.05). Seventy-one percent of patients with large tumors were oriented to time compared to 97% for small lesions (P < 0.01). Emergence from anesthesia was similar for spinal surgery patients and patients with small brain tumors. CONCLUSION: Patients undergoing craniotomy for large intracranial mass lesions awaken more slowly than patients after spinal surgery or craniotomy for small brain tumor.

Anesthesia↗
PubMed1996

Effect of methimazole with or without exogenous L-thyroxine on serum concentrations of thyrotropin (TSH) receptor antibodies in patients with Graves' disease.

Medical treatment of Graves' disease involves use of antithyroid drugs with or without the addition of exogenous L-T4. There have been conflicting reports as to whether the addition of T4 reduces TSH receptor antibodies and improves remission rates more than antithyroid drugs alone. To further examine the effect of drug therapy on serum concentrations of TSH receptor antibodies. 70 patients with Graves' disease were treated with methimazole (Tapazole) alone until they were euthyroid. Then they were randomized to receive either: 1) methimazole alone in a dose sufficient to normalize TSH (0.3-5.4 mIU/L; Group 1); 2) 30 mg methimazole daily plus sufficient T4 (Synthroid) to maintain TSH in the high-normal range (2.0-5.4 mIU/L; Group 2); or 3) 30 mg methimazole daily plus sufficient T4 to suppress TSH to below 0.6 mIU/L (Group 3). The duration of treatment in all groups was 18 months. At baseline and after 6 and 18 months, TSH receptor antibodies were measured both by the ability of patients' sera to stimulate cAMP production by FRTL-5 cells (thyroid-stimulating Ig) and by the ability of patients' sera to inhibit binding of radiolabeled TSH to solubilized porcine thyroid membranes (TSH-binding, inhibiting Ig). Thyroid-stimulating Ig(TSI) and TSH-binding, inhibiting Ig(TBII) concentrations were similar among the three groups at baseline. Mean baseline TSI (expressed as the percent of normal control) for all patients combined was 306 +/- 21%. Mean baseline TBII (expressed as percent inhibition of TSH binding) was 38 +/- 2%. TSI was elevated in 85% and TBII was elevated in 75% of patients at baseline. After 18 months, TSI was elevated in 64% of patients, and TBII was elevated in 28%. Serum TSI decreased by 36 +/- 5% during the study, and there was no significant difference in the degree of reduction among the three groups (P = 0.99). Serum TBII decreased by 59 +/- 3%, and there also was no significant difference among the groups (P = 0.83). At baseline, serum TBII correlated with free T4 (r = 0.33, P < 0.01), total T3 (r = 0.55, P < 0.01), and thyroid size (r = 0.35, P < 0.01). There was no correlation between TSI and any of the baseline parameters or between TSI and TBII at any timepoint. In conclusion, we found that the addition of T4 to methimazole does not result in a greater decrease in TSH receptor antibody concentrations than treatment with methimazole alone. From these results, we would predict no difference in remission rates among these patients, but confirmation of this prediction will need to await long-term follow-up of these subjects.

Adolescent↗
PubMed1996

Comparison between Centcor CA 125 and CA 125 II assays.

Second generation CA 125 assays are expected to replace the original CA 125 assays soon. This study compares the Centcor CA 125 II and the original Centcor CA 125 assays in 50 women: 34 with gynecologic cancers, 5 with benign conditions and 11 healthy. The serum values obtained by both assays were not statistically different and showed high correlation especially for values < 300 U/ml. Two patients who had false elevation of CA 125 by the original assay secondary to human antimouse antibody had normal values by the CA 125 II assay. It is concluded that CA 125 serum values obtained by the Centcor CA 125 II assay correlate well with the values obtained by the original Centcor CA 125 assay especially for values < 300 U/ml and are less likely to show elevated false positive results secondary to human antimouse antibody.

Adult↗
PubMed1995

Effects of fluid-induced shear on articular chondrocyte morphology and metabolism in vitro.

This study tested the effects of fluid-induced shear on high density monolayer cultures of adult articular chondrocytes. Fluid-induced shear (1.6 Pa) was applied by cone viscometer to normal human and bovine articular chondrocytes for periods of 24, 48, and 72 hours. At 48 and 72 hours, fluid-induced shear caused individual chondrocytes to elongate and align tangential to the direction of cone rotation. Fluid-induced shear stimulated glycosaminoglycan synthesis by 2-fold (p < 0.05) and increased the length of newly synthesized chains in human and bovine chondrocytes. In human chondrocytes, the hydrodynamic size of newly synthesized proteoglycans also was increased. After 48 hours of fluid-induced shear, the release of prostaglandin E2 from the chondrocytes was increased 10 to 20-fold. In human chondrocytes, mRNA signal levels for tissue inhibitor of metalloproteinase increased 9-fold in response to shear compared with the controls. In contrast, mRNA signal levels for the neutral metalloproteinases, collagenase, stromelysin, and 72 kD gelatinase, did not show such major changes. This study demonstrated that articular chondrocyte metabolism responds directly to physical stimulation in vitro and suggests that mechanical loading may directly influence cartilage homeostasis in vivo.

Aged↗
PubMed1995

Inhibitory effects of tamoxifen and tumor necrosis factor alpha on human glioblastoma cells.

We reported previously that tumor necrosis factor alpha (TNF alpha) inhibited proliferation and invasiveness of human malignant glial cells. Because tamoxifen, an estrogen antagonist, has also been shown to inhibit growth of such cells, we hypothesized that a combination of tamoxifen and TNF alpha might be more effective than either reagent alone. TNF alpha (1-100 ng/ml) or tamoxifen (80 ng/ml-2 micrograms/ml) alone inhibited proliferation of a human glioblastoma cell line (WITG3) in a dose-dependent fashion; in combination, tamoxifen and TNF alpha yielded additive growth inhibition. Apoptotic cells characterized by nuclear fragmentation were detectable after 48 h of TNF alpha or tamoxifen exposure and were significantly increased by combination treatment. In non-neoplastic human astroglia and fibroblasts, proliferation was unaffected by tamoxifen, and enhanced by TNF alpha as previously reported. Staurosporine (2-50 nM), which has been reported to augment the effects of TNF alpha, was less effective than tamoxifen against WITG3 and, in addition, was markedly inhibitory to non-neoplastic glial cells. Binding studies yielded no evidence of WITG3 estrogen or progesterone receptors, nor of tamoxifen effects on TNF alpha receptors. Data suggest that TNF alpha and tamoxifen in combination display growth-regulatory properties, which (a) are more inhibitory to human glioblastoma cells than either agent alone, (b) do not affect non-neoplastic glia, (c) do not require either estrogen/progesterone receptors or alteration of external TNF alpha receptors, and (d) may involve apoptosis.

Alkaloids↗
PubMed1995

Plant uptake of fluoride in irrigation water by ladyfinger (Abelmorchus esculentus).

Because of suggestions that food is a rich source of fluoride to humans and the absence of permissible and upper limits of fluoride for irrigation water, plant uptake studies were conducted using fluoride-rich irrigation water. Ladyfinger was grown in sand and soil cultures for 18 wk and the accumulation of fluoride in various plant parts was studied. The potential for ingestion of fluoride by humans through this route was also considered. The percentage uptake was greater in sand-cultured plants than in soil-cultured plants. The root accumulates most of the fluoride supplied through irrigation water and the fruit accumulates the least. Up to 120 mg fluoride/litre of irrigation water did not harm the plants. The ingestion of fluoride by humans from plants irrigated with water containing 10 mg fluoride/litre would be 0.20 mg per 100 g ladyfinger.

Fluorides↗
PubMed1995

Many component model and its parameters to fractionated irradiation.

PURPOSE: In this study, a many component model has been formulated to address the contribution of various bio-molecules in radiation induced biological damage and this model is fitted to radiation isoeffect data to evaluate the parameter alpha/beta. MATERIAL AND METHODS: Every living cell contains a number of organic and inorganic molecules which may act as targets to lead radiation induced damage. During irradiation, many kinds of physical, chemical and biological products are produced which are due to active participation of aforesaid molecules. The many component model, hereinafter called linear-quadratic-cubic (LQC) model, is an attempt to provide a better mathematical formulation which could demonstrate the contribution of various kinds of biomolecules in biological effect of radiation. This model has only one independent parameter alpha/beta and a number of dependent parameters which are the derivatives of alpha/beta. RESULTS: Three methods, for testing the fit of the proposed model and deriving the values of alpha/beta, are employed using multifractionation isoeffect data. These methods, i.e. (logDm-logDn) versus (dn-dm) plot, SFe-plot and logD versus d plot, provide their respective values of alpha/beta as 12.50 Gy, 12.51 Gy and 12.54 Gy for spleen. 7.41 Gy, 7.79 Gy and 7.42 Gy for kidney, 15.87 Gy, 15.09 Gy and 14.69 Gy for colon with 3 h interval, 12.50 Gy, 12.84 Gy and 12.45 Gy for colon with 12 h interval and 8.47 Gy, 8.84 Gy and 8.51 Gy for colon with 24 h interval. Since other parameters of the model are the derivatives of alpha/beta therefore can be derived using the values of alpha/beta. DISCUSSION: Graphical representation of afore said sets of data show that the plotted points have a certain amount of scattering which is not at the wider scale and can be well or less well described by a straight line. CONCLUSION: This model eliminates the shortcomings of LQ model and provides a satisfactory explanation of various radiobiological processes occurring during and after irradiation.

Animals↗
PubMed1994

Effect of combination therapy in Mycobacterium paratuberculosis infected rabbits.

Rabbits, infected with M paratuberculosis of caprine origin, were treated with streptomycin sulphate and rifampicin in combination with levamisole hydrochloride for a period of 2 months. Marked clinical response including significant rise in total serum protein, albumin and globulin were recorded in treated groups. Highly significant higher leucocyte migration inhibition indicating enhanced CMI reaction, occurred in rabbits treated for 4 weeks. Complete elimination of M. paratuberculosis from faeces, intestines and mesenteric lymph nodes was observed. They were also absent from spleen, kidneys, lungs and liver of rabbits treated with rifampicin and levamisole, whereas were present in lungs of the rabbits administered with streptomycin and levamisole. Absence of characteristic lesions of paratuberculosis and evidence of regenerative reaction were observed in visceral organs of rabbits treated with rifampicin and levamisole. Effectiveness of rifampicin is attributed to its effect on lymphocyte, the primary cell involved in cell mediated immunity. Rifampicin-levamisole combination appeared superior to streptomycin-levamisole in eliminating the infection of M. paratuberculosis from infected rabbits. Approximate cost of treatment was calculated to be Rs 8.50 per kg body weight. Cattle, sheep and goats, if treated in early stage of infection may recover from paratuberculosis.

Animals↗
PubMed1993

Studies on the leaching of fluoride in tea infusions.

In order to assess the levels of fluoride ingestion through intake of tea, studies were conducted with four different brands of tea leaves commonly available in the Indian market. Four most prevalent methods for the preparation of tea with various contact times (2,4,6,8 and 10 min) of tea leaves with water show that: (a) leaching of fluoride is least in case of leaf tea as compared to powdered tea (F levels increasing with decreasing grain size); (b) leaching of fluoride reaches a maximum after a contact of about 6 min; (c) there is no difference between levels of fluoride with or without addition of milk in the English style where tea leaves are not boiled, while for the Indian style, addition of milk and subsequent boiling resulted in reduction of fluoride levels and (d) ingestion of fluoride per cup of tea ranged from 1.55 mg/l to 3.21 mg/l amounting to an intake per day per person of fluoride between 0.3 to 1.9 mg.

Fluorides↗
PubMed1993

Endocrine disorders (parathyroid hormone).

In summary, precise PTH measurements have been difficult and complex as a result of low circulating concentrations of biologically active hormone and the immunoheterogeneity of circulating PTH molecules. The differences in secretion rates and metabolism of various PTH fragments in different clinical disorders further complicated the interpretation of various radioimmunoassable PTH levels. In recent years, the development of two-site or intact immunometric assays represents significant advancements in PTH measurement. These assays, for the first time, provide the long-awaited sensitivity and precision of PTH measurement. The IRMA assay has certainly overcome the difficulties in accurately diagnosing parathyroid disorders and the difficulties in the differential diagnosis of hypercalcemia. Above all, these assays are more convenient and more specific in patients with compromised renal function.

Calcium↗
PubMed1993

Dual mechanism of perturbation of thyrotropin-mediated activation of thyroid cells by antibodies to the thyrotropin receptor (TSHR) and TSHR-derived peptides.

To further define the epitopes with which anti-TSH receptor (anti-TSHR) antibodies react and mediate their biological effects, we used antibodies against the extracellular domain of TSHR (ETSHR) protein and nine peptides derived from the ETSHR. Peptides were chosen based on their predicted immunogenicity as well as their uniqueness to the TSHR. Antipeptide antibodies showed varying degrees of reactivity against ETSHR, with antipeptide-2-(352-366) and -3A-(357-372) showing relatively stronger reactivity with the receptor. Antibodies were tested for their ability to stimulate thyroid cells and were found to be ineffective in causing both cAMP release and iodide uptake. However, anti-3A and anti-ETSHR showed blocking TSHR antibody (TSHRAb) activities of 76.9% and 79.7%, respectively, which were significantly different (P < 0.005) compared to that of preimmune serum. Anti-2 and -91 (AA 32-46) also showed blocking TSHRAb activities of 37.5% and 35.6%, respectively (P < 0.05). Antisera were also tested for their ability to block TSH binding to thyroid membranes in a RRA. Anti-ETSHR, but not any of the antipeptide antibodies, displayed TSH binding inhibitory immunoglobulin activity. These findings suggest that there might be different mechanisms that mediate blocking TSHR antibody activity. One mechanism involves the inhibition of TSH binding to the receptor, and the other probably involves a step subsequent to TSH binding.

Adenylyl Cyclases↗