Biomedical subjects

N Kundu

Publications and source records attributed to N Kundu.

At least 19 recordsLinked to original sources

PubMed2005

Geochemistry of soil around a fluoride contaminated area in Nayagarh District, Orissa, India: factor analytical appraisal.

Fluoride contamination in soil was studied in the vicinity of a hot spring in Nayagarh district of Orissa. Both bulk soil from 0 to 30 cm depth and profile soils from 0 to 90 cm depth were analyzed for total fluoride (F(t)) and 0.01 M CaCl(2) extractable fluoride (F(ca)), major elements, pH, EC and Organic Carbon (OC). High concentrations of both F(t) and F(ca) were observed in the area surrounding the hot spring and the village of Singhpur. Principal factor analysis (PFA) on the parameters of the bulk soils suggests that two major chemical processes due to three factors, control the soil geochemistry of the area. Factor-1 contributes 37.11% of the total variance and is strongly loaded with Al, Si, Fe, F(t)and F(ca), and explains the fluoride enrichment of the soil, whereas the second and the third factors contribute 16.6 and 12.2%, respectively and explain the controlling process of carbonate precipitation and soil alkalinity. Multiple regression analysis of the scores of the factors was performed to derive a fluoride contamination index in soil. The magnitude of the factor effect on the contamination index follows the order of Factor-1 > Factor-2 > Factor-3. The spatial distribution of the contamination index is used to classify the area into highly contaminated, moderately contaminated and uncontaminated zones.

Environmental Monitoring↗

PubMed2005

Frequency-dependent prey-selection of predacious water bugs on Armigeres subalbatus immatures.

BACKGROUND & OBJECTIVES: The predatory behaviour with reference to the frequency-dependent prey-selection of the water bugs Sphaerodema annulatum Fabricius and S. rusticum Fabricius was studied in the laboratory using the IV instar larvae and pupae of Armigeres subalbatus as prey to ascertain their efficacy as predator of mosquito immatures. METHODS: Field collected adult morphs of the water bugs were allowed to predate on larvae and pupae provided in different ratios and densities as per the model of Greenwood and Elton' for a fixed time period. The data obtained on their predation rate were analysed with respect to the model parameters, lnV--the frequency independent component and b--the frequency dependent component of selection. RESULTS: It was found that the prey-selection was dependent on the relative numbers of prey available, favouring apostatic selection. The b values and lnV values for S. annulatum were 0.54 +/- 0.01 and 0.92 +/- 1.04 respectively whereas the corresponding values for S. rusticum were 0.71 +/- 0.03 and 0.17 +/- 1.57 respectively. INTERPRETATION & CONCLUSION: The selection of preys by the water bugs was dependent on the relative number of the prey forms and thus they are expected to predate on the form more abundant in a heterogeneous prey population and adversely affect the adult emergence.

Animals↗

PubMed2004

Predatory efficiency of the water bug Sphaerodema annulatum on mosquito larvae (Culex quinquefasciatus) and its effect on the adult emergence.

The daily number of IV instar larva of Culex quinquefasciatus killed, rate of pupation and adult emergence was noted in presence of the predatory water bug Sphaerodema annulatum for a period of seven consecutive days, experimentally, in the laboratory. The rate of IV instar larva killed by the water bugs on an average was 65.17 per day. The rate of pupation ranged between 7.6 and 48 in control while in presence of water bugs it ranged between 6 and 35. The rate of adult emergence in control experiments varied between 1.4 and 4.8 per day, which was reduced to only 0.4-28.8 per day in case of the water bugs. The results clearly indicate that the water bugs on its way of predation reduces the rate of pupation and adult emergence of Cx. quinquefasciatus significantly which calls for an extensive field trials.

Animals↗

PubMed2001

Increased cyclooxygenase-2 (cox-2) expression and activity in a murine model of metastatic breast cancer.

Elevated prostaglandin E(2) (PGE(2)) production is a common feature of human malignancies. This activity has often been attributed to increased metabolic activity of the cyclooxygenase enzymes, although a direct comparison of these 2 parameters i.e., prostaglandin production and cox protein expression, is rarely performed in the same malignant tissue. Using a murine model of metastatic breast cancer, we show that PGE(2) levels are positively correlated with increased tumorigenic and metastatic potential. Because prostaglandin synthesis is a product of 2 isoforms of the cyclooxygenase enzyme, we examined the expression and activity of both isoforms. All tumor cell lines examined, regardless of phenotype, express both cox-1 and cox-2 proteins in vitro. In contrast to the uniform cox-2 expression in vitro, only tumors resulting from the transplantation of metastatic cell lines express cox-2 in vivo. Cox-1 is detected in both metastatic and nonmetastatic tumors. Thus, this is the first evidence that, in the tumor milieu, cox-2 expression can be regulated differently in metastatic vs. nonmetastatic lesions. Examination of PGE(2) synthesis in vitro reveals that nearly complete inhibition of prostaglandin synthesis occurs in the presence of either indomethacin, which inhibits both isoforms, or NS398, which is selective for the cox-2 isoform. Thus, even though cell lines express both isoforms, the majority of the prostaglandin synthesis stems from the activity of the inducible, cox-2 isoform. Likewise, cell growth is inhibited by both indomethacin and NS398 in a dose-dependent manner, albeit at higher drug concentrations than required to ablate PGE(2) synthesis. Despite the inhibition of prostaglandin synthesis, the cox-2 enzyme levels (protein and mRNA) were increased by either indomethacin or NS398.

Animals↗

PubMed1999

Interleukin-10 gene transfer activates interferon-gamma and the interferon-gamma-inducible genes Gbp-1/Mag-1 and Mig-1 in mammary tumors.

Expression of IL-10 as a transgene inhibits murine mammary tumor growth and metastasis. Using differential display methodology, we sought genes whose expression was modulated by IL-10. We compared mRNA isolated from parental murine mammary 66.1 tumors, as well as tumors derived from neo(r)-transfected cells and 6 different IL-10-expressing cell lines. We identified 2 cDNA products that were up-regulated in all 6 IL-10-expressing tumors in comparison to parental and 66-neo tumors. One cDNA corresponds to the murine guanylate-binding protein gene Gbp-1/Mag-1. The other cDNA corresponds to the chemokine Mig-1 (monokine induced by IFN-gamma). Both genes were originally identified in IFN-gamma-activated macrophages or macrophage cell lines. We now report that cultured mammary epithelial tumor cell lines also express both genes in response to treatment with IFN-gamma and LPS. Furthermore, IFN-gamma mRNA is elevated in IL-10-expressing tumors in comparison with parental or neo-transfected tumors. Thus, high-level expression of IL-10 as a transgene results in activation rather than suppression of IFN-gamma as well as 2 IFN-gamma-inducible genes. Up-regulation of host IFN-gamma is critical to anti-tumor activity since IL-10 no longer inhibits tumor growth in hosts with a deletion in the IFN-gamma gene. Additionally, Gbp-1/Mag-1 and Mig-1 gene induction no longer occur in IFN-gamma mutant mice.

Animals↗

PubMed1998

IL-10 gene transfer to intracranial 9L glioma: tumor inhibition and cooperation with IL-2.

This study examines the effects of interleukin-10 (IL-10) and combination IL-10 + IL-2 gene transfer on experimental brain tumor growth in vivo. 9L gliosarcoma cells were engineered to stably express murine IL-10 (9L-IL-10 cells) and implanted subcutaneously or to the caudate/putamen of syngeneic rats. The growth of tumors expressing IL-10 was substantially reduced compared to that of control tumors (p < 0.05). Intracranial tumors expressing IL-10 and IL-2 were established by co-implanting 9L-IL-10 cells with endothelial cells engineered to express IL-2. At 14 days post-implantation, tumors expressing IL-10 + IL-2 were 99% smaller than control-transfected tumors (p < 0.0001). This extent of anti-tumor effect could not be achieved by expression of IL-10 or IL-2 alone within tumors. Neither IL-10 nor a combination of IL-10 + IL-2 gene delivery inhibited tumor growth in severe combined immunodeficient (SCID-Beige) mice (p > 0.05). Immunohistochemical analysis revealed that IL-10 + IL-2 gene delivery markedly increased T-cell infiltration within the striatum ipsilateral to tumor cell implantation. These findings establish that IL-10 expression, particularly in combination with IL-2 expression, can have significant immune-dependent anti-tumor actions within intracranial gliomas.

Animals↗

PubMed1998

Interleukin-10 gene transfer inhibits murine mammary tumors and elevates nitric oxide.

Transfection of cDNA for IL-10 into line 66.1 murine mammary tumor cells results in marked suppression of tumor growth and metastasis. Others have reported that nitric oxide has potent antitumor activity and IL-10 is known to regulate the inducible isoform of nitric oxide synthase (iNOS) expressed in macrophages. We identified nitric oxide production in mammary tumors as indicated by electron paramagnetic resonance detection of nitric oxide-hemoglobin (NO-Hb). IL-10 expression resulted in elevated levels of NO-Hb in mammary tumors. Immunohistochemical examination of mammary tumors for iNOS protein revealed few positively staining cells in parental or control neo-transfected tumors but strong iNOS staining in all IL-10 transfected tumors, consistent with the NO-Hb data. To determine if mammary epithelial tumor cells themselves, express nitric oxide synthase activity, cultured tumor cells were treated with pro-inflammatory cytokines and nitrite accumulation was assessed in the conditioned medium. All IL-10 producing cell lines accumulated uM concentrations of nitrite in response to short term (24 hr) cytokine stimulation. Cells not expressing IL-10 (parental and neo-transfectants) accumulated no nitrite under similar culture conditions. After longer stimulation (48 hr), parental and 66-neo cells accumulated lower amounts of nitrite. IL-10 gene transfer is associated with increased iNOS protein expression and enzymatic activity detected both in vitro and in vivo. Our findings suggest that the antimetastatic and antitumor activity of IL-10 is related to enhanced production of nitric oxide.

Adenocarcinoma↗

PubMed1997

Interleukin-10 inhibits tumor metastasis, downregulates MHC class I, and enhances NK lysis.

We have engineered highly aggressive murine mammary tumor cell line 410.4 to express interleukin-10 (IL-10) and compared the behavior in vivo of these cells to parental 410.4 and 410.4 transfected with the control plasmid (410.4-neo). Transplantation of parental 410.4 and 410.4-neo tumor cells to syngeneic mice resulted in progressive growth and death from pulmonary metastases. In contrast, both subcutaneous growth and metastatic disease were completely inhibited by IL-10 expression. We had shown previously that the antimetastatic activity of IL-10 is expressed in T-cell-deficient mice but is lost when NK activity is suppressed. This study confirms that IL-10 is dependent on NK activity, since no therapeutic effect is seen in C.B-17/IcrCrl-SCID/Beige mice which lack T, B, and NK cell function. We compared the sensitivity to NK lysis of four IL-10-expressing clones with 410.4 and 410.4-neo and found that IL-10 expression resulted in enhanced NK lysis of all four clones. Furthermore, IL-10 expression was correlated with decreased surface expression of MHC class I Kd, Ld, and Dd. Pretreatment of IL-10-expressing cell lines with IFN-gamma reversed the class I downregulation and reduced the sensitivity of these cells to NK lysis. Taken together, these studies in vitro and in vivo are consistent with a mechanism by which IL-10 expression downregulates class I expression, leading to enhanced NK lysis of tumor cells, resulting in control of metastatic disease.

Animals↗

PubMed1997

Expression of the RET/PTC fusion gene as a marker for papillary carcinoma in Hashimoto's thyroiditis.

Hashimoto's thyroiditis is an inflammatory disease of the thyroid gland with autoimmune etiology. Patients afflicted with Hashimoto's have a higher risk of thyroid malignancies such as papillary thyroid carcinoma. In the present study, we investigated the frequency of papillary thyroid carcinoma specific genes in patients diagnosed with Hashimoto's disease. The newly identified oncogenes RET/PTC1 and RET/PTC3 provide useful and specific markers of the early stages of papillary carcinoma as they are highly specific for malignant cells. Using a sensitive and specific reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we found messenger RNA (mRNA) expression for the RET/PTC1 and RET/PTC3 oncogenes in 95% of the Hashimoto's patients studied. All Hashimoto's patients presenting without histopathologic evidence of papillary thyroid cancer showed molecular genetic evidence of cancer. These data suggest that multiple, independent occult tumors exist in these patients at high frequency.

Adult↗

PubMed1996

Antimetastatic and antitumor activities of interleukin 10 in a murine model of breast cancer.

BACKGROUND: Interleukin 10 (IL-10) is a potent immunoregulatory cytokine. It inhibits some cell functions, including T-helper (Th1) cell activity (i.e., interleukin 2 and interferon gamma production), and stimulates other functions such as a natural killer (NK) activity. In mice, IL-10 suppresses tumorigenicity in a xenograft system using a nonmetastasizing hamster cell line. PURPOSE: We evaluated the antitumor and antimetastatic properties of IL-10 in syngeneic immunocompetent and immunocompromised murine hosts. METHODS: Using the plasmids pBMGneo and pBMGneo.IL-10, we transfected the highly malignant murine mammary tumor cell lines 410.4 and 66.1 (transfectants designated as 410.4-IL10 and 66.1-IL10, respectively) to stably express IL-10 (2-100 U IL-10/2.5 x 10(5) cells per 48 hours). Tumorigenic and metastatic activities of the parent and transfected cells w ere measured in immunocompetent, syngeneic BALB/cByJ mice as well as in immunocompromised C.B-17/IcrCrl-SCID/Beige mice. RESULTS: Tumor growth was completely inhibited following inoculations of 5 x 10(6)410.4-IL10 cells in immunocompetent, syngeneic BALB/cByJ mice. This inoculum contains 100 times the minimum cell number required for 100% tumor incidence. In contrast, tumor growth following the inoculation of parental 410.4 or 410.4-neo cells was progressive, resulting in death of animals from pulmonary metastases at days 40-50 and transplantation. The tumorigenicity of 66.1-IL-10, compared with that of its parent cell line, was also significantly abrogated by IL-10 expression. Furthermore, in immunocompetent mice, the metastatic potential of both 410.4-IL10 and 66.1-IL10 was also completely inhibited. In immunocompromised C.B-17/IcrCrl-SCID/BR or C.B-17/IcrCrl-SCID/Beige mice, subcutaneous implants of 410.4-IL10 grew progressively, but growth was inhibited significantly in comparison to that produced by the parental 410.4 or 410.4-neo cells. In spite of the more limited efficacy of IL-10 against tumor growth in immunocompromised mice, spontaneous metastasis of 410.4-IL10 cells in C.B-17/IcrCrl-SCID/BR mice was inhibited by 90%. When NK activity was suppressed by asialoGM1 ganglioside antibody in BALB/cByJ mice or in C.B-17/IcrCrl-SCID/Beige mice, the antimetastatic effect of IL-10 was lost. CONCLUSIONS: These data show for the first time that IL-10 is a potent antimetastatic agent that is effective in immunocompromised hosts. This effect thus appears to be relatively independent of T-cell function but is dependent on NK activity. In contrast, the inhibitory effect of IL-10 on tumorigenicity relies on T-cell function. IMPLICATIONS: Based on the recent observation of others that IL-10 has little toxicity when administered systemically to human volunteers and also on the findings of this study that it has antitumor and antimetastitic properties in mice, possible use of IL-10 in the treatment of human metastatic cancers deserves consideration.

Animals↗

PubMed1995

Sublethal oxidative stress inhibits tumor cell adhesion and enhances experimental metastasis of murine mammary carcinoma.

We have postulated that murine mammary tumor progression is fueled, in part, by tumor-associated macrophages that deliver sub-lethal oxidative stress to tumor cells. In the present study, we determined whether oxidative stress would affect murine mammary tumor cell attachment to laminin and fibronectin, critical functions in the metastatic process. Sublethal oxidative stress generated by exposure of cells to hydrogen peroxide (H2O2, 1-1000 microM/L) inhibited tumor cell attachment to immobilized laminin or fibronectin. This oxidant effect was blocked in the presence of catalase which removes H2O2. The inhibitory effect on attachment was rapid, with significant inhibition occurring at 5 min; total inhibition was achieved at 60 min with 1 mM H2O2. The oxidative stress effect was partially reversible at 20 h post-treatment and occurred at concentrations of H2O2 that do not adversely affect cell viability or growth. Pretreatment of tumor cells with H2O2 or hypoxanthanine and xanthine oxidase (to generate superoxide radical and H2O2) prior to intravenous injection, enhanced experimental lung tumor colony formation. The enhancement of experimental metastatic potential with enzyme-generated oxidative stress was completely reversed by catalase; the H2O2-mediated enhancement was only partially reversed with catalase. Thus, treatments that inhibit tumor cell attachment to extracellular matrix proteins in vitro enhance experimental metastasis in vivo.

Adenocarcinoma↗

PubMed1993

Normal thrombin binding leads to greater fibrinogen binding and increased platelet aggregation in spontaneously hypertensive rats.

This study was conducted to determine the mechanisms of increased platelet reactivity to thrombin in hypertension. Thrombin induced significantly greater platelet aggregation in spontaneously hypertensive (SHR) than in normotensive (Wistar Kyoto, WKY) rats. Fibrinogen and thrombin binding to platelets was determined using [125I]-fibrinogen and [125I]-thrombin respectively. Increased platelet aggregation in SHR correlated with thrombin-induced greater binding of fibrinogen to SHR than to WKY platelets. However, the number of thrombin receptors (binding sites/platelet) in WKY (19,500 +/- 3,000) and SHR (23,100 +/- 3,000) as well as thrombin dissociation constants were statistically similar in WKY (1.17 +/- 0.2 microM) and SHR (1.62 +/- 0.27 microM) platelets. Fura 2/AM, a fluorescent calcium indicator, loaded platelets were used to quantify the platelet ionized calcium ([Ca2+]i). The [Ca2+]i in unstimulated SHR and WKY platelets was essentially the same. In a calcium poor medium, thrombin-induced a 35% greater increase in [Ca2+]i in SHR than in WKY platelets. These data, taken together with our earlier observations that thrombin induces a significantly greater hydrolysis of phosphoinositide (Thromb. Res. 49, 5-21, 1988), lead us to suggest that thrombin-induced increased generation of inositol 1,4,5-trisphosphate and diacylglycerol induces greater fibrinogen binding and consequently increased aggregation in SHR than WKY platelets. The finding that the thrombin binding isotherms are similar in WKY and SHR platelets suggests that increased platelet sensitivity to thrombin in hypertension may be due to altered signal transduction and not due to changes in the number or affinity of thrombin receptors.

Animals↗

PubMed1986

Effect of the oxytocin challenge test on levels of maternal serum unconjugated serum estriol and estetrol pre- and post-test in high-risk pregnancies.

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Estetrol↗

PubMed1984

A multifactorial pregnancy outcome index.

In the present study pregnancy outcome is defined as a combination of seven relatively independent factors. Outcome scores were assigned to each subject on the basis of the number of pregnancy and labor-related factors that were satisfied. An outcome index of seven indicated an excellent outcome, and an index value of zero indicated the poorest outcome. Clinical data for 821 subjects, including a selected sample of 102 high-risk patients, were recorded using the Hollister Record System forms. The contribution of each of these factors to the overall outcome was estimated by statistical analysis of all data from the 821 subjects. Validation of this multifactor index of pregnancy outcome was obtained by correlation analysis with established factors such as the number of previous term pregnancies, live births, abortions, and present preexisting risk factors. In addition, retrospective analyses relating pregnancy outcome index with maternal serum unconjugated estriol, zinc, and copper obtained from 102 high-risk patients, revealed that copper level at all third trimester gestations was systematically and significantly related to outcome level while no such relationship emerged from comparisons with estriol and zinc. Good and poor outcomes were related to low and high copper values, respectively. The results of this exploratory study suggest that maternal serum copper levels may be an alternative predictor of pregnancy outcome.

Abortion, Spontaneous↗

PubMed1983

Salivary unconjugated estriol levels in normal third trimester pregnancy - direct correlation with serum levels.

A radioimmunoassay for salivary unconjugated estriol concentration during the third trimester of normal pregnancy is described. The performance characteristics of the method were established by determining the non-specific binding, the blank value of the endogenous estriol free ("stripped") saliva, the recovery experiment and intra- and interassay coefficient of the variations. The corresponding serum samples were also analyzed by the same method. An excellent correlation was found between salivary and serum estriol concentrations.

Estriol↗

PubMed1981

Comparison of serum unconjugated estriol and estetrol in normal and complicated pregnancies.

It has been reported that determinations of maternal serum unconjugated estriol (E3) and estetrol (E4) concentrations provide clinicians with more or less identical information on fetal status. If this is true, then theoretically the levels of E3 should be equally correlated with those of E4 in all conditions of pregnancy. To resolve this question, a study of the relationship between E3 and E4 was performed before labor in normal and complicated pregnancies. In normal pregnancy, they were highly correlated (r = .683, P less than .0001); in complicated cases, they were still correlated, but at a lower level (r = .522, P less than .003). To determine the effect of labor on this correlation, E3 and E4 levels were measured in normal subjects during labor as well as in the corresponding fetuses. The correlations between material E3 and E4, maternal and fetal E4, maternal and fetal E3, and fetal E3 and E4 were highly significant. A similar study with complicated pregnancies, however, indicated no such correlation except between fetal E3 and E4. In addition, day-to-day variability of serial measurements of E3 and E4 on an individual basis was determined in normal and diabetic subjects. The variability was qualitatively determined graphically and quantitatively determined algorithmically. The results of calculated individual variabilities indicated that the variability of E4 was less than that of E3 in most cases. It is therefore concluded that complications in pregnancy and the onset of labor have some effect on E3-E4 correlations, and that measurement of E4 has an additional advantage due to less variability.

Estetrol↗

PubMed1981

Fetal and maternal serum copper levels before and during labor in normal and complicated pregnancies.

The effect of labor on maternal serum copper levels was determined in normal and complicated pregnancies. The mean value +/- SD (3.16 +/- 0.48 micrograms/ml) in 82 clinically normal subjects at term during labor was compared with that (2.22 +/- 0.49 micrograms/ml) obtained from 50 controls matched for gestational age who were not in labor. Similarly, the mean value in labor (3.56 +/- 0.46 micrograms/ml) in 25 subjects with a complicated pregnancy was compared with that (2.87 +/- 0.43 micrograms/ml) obtained from 25 similar subjects prior to labor. A statistically significant difference (P less than .001) was observed in both comparisons. Copper levels in the corresponding fetal serum from the subjects in labor (normal and complicated) were compared with those of the maternal serum samples. The mean value of fetal serum samples in mothers with complications was higher than that in normal mothers, but the difference was not statistically significant. This trend of a rise in serum copper level during labor was further confirmed by analysis of the same subject during and before labor in normal (12 subjects) and complicated pregnancies (9 subjects). Moreover, maternal serum estriol and estetrol levels were determined from the same samples in the 4 groups to find a possible relationship with the corresponding copper levels. No statistically significant correlation was noted. A possible explanation for the rise of the serum copper level with the onset of labor and its clinical implications are also discussed.

Copper↗

PubMed1980

Endocrine assessment of high-risk pregnancies.

For critical obstetrical judgment, no single laboratory test or biophysical technique has proved completely effective in preventing fetal deaths. Endocrine assessment of high-risk pregnancies has proved helpful in managing pregnancies with diabetes, hypertension, third trimester bleeding, suspected IUGR, and postdate pregnancies. No single endocrine test has proved to be effective in all cases, and much research remains to be done. Of the current endocrine factors being evaluated when all factors are considered, serum unconjugated estriol would appear to be the best predictor of fetal distress or well-being. However, it must be remembered that interpretation of laboratory values is difficult, and that there are many false positives and false negatives. Perhaps the greatest problem with estriol interpretation is short-term and daily fluctuations. If the estriol values are used as the only indicator for following high-risk pregnancies, there is a very likely possibility of delivering a normal premature infant that was wrongly diagnosed as having fetal distress. In the following high-risk pregnancies with estriols, the delivery decision should not be based on a single factor. Rather, the decision to deliver should be based on the estriol values, monitoring of the fetal heart rate (rhythm strip or OCT), amniotic fluid evaluation for fetal lung maturity, and clinical judgment.

Adrenal Glands↗