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N Kundu

Publications and source records attributed to N Kundu.

35 records · Page 2Linked to original sources

Sequential determination of serum human placental lactogen, estriol, and estetrol for assessment of fetal morbidity.

Serial measurements were made of the concentrations of maternal serum human placental lactogen (hPL) (300 determinations), estriol (E3) (460 determinations), and estetrol (E4) (275 determinations) in normal human pregnancy during the third trimester period. Simultaneous determinations of serum hPL, E3, and E4 were also made sequentially on blood samples from 6 diabetic and 5 toxemic pregnant women to ascertain the relative usefulness of these parameters as indicators of fetal welfare. In uncomplicated diabetic patients controlled with insulin, all parameters increased with gestational age. In three pregnancies complicated by severe toxemia in which fetal distress progressed to intrauterine fetal death, both serum E3 and E4 levels decreased progressively, but E4 concentration started to decrease at least 1 day earlier than E3 prior to fetal death. In other women, the E4 levels appeared to drop or decrease significantly whereas the E3 levels remained almost unchanged. Daily hPL levels remained low in chronic fetal distress and, therefore, appeared to be of minimal value for predicting either intrauterine death or acute fetal distress. Therefore, serum E4 measurement seems to provide a more sensitive and reliable indicator of fetal morbidity than the measurement of serum E3 during toxemic pregnancies.

Estetrol↗

Production of antisera against contraceptive steroids.

A four step synthesis of 6-(0-carboxymethyl) oximinoethynylestradiol is reported. This compound, 6-(0-carboxymethyl) oximinomestranol, the 3-(0-carboxymethyl) oximes of norethindrone and norgestrel and the 3-hemisuccinate of ethynylestradiol were synthesized and conjugated with bovine serum albumin. Rabbits were immunized at 3 dose levels of haptene (20, 66 and 200 nmoles) and eight weeks later with a booster containing 66 nmoles of haptene. The antibody titer and association constant of responding rabbits was nearly independent of dose although most antibody production occurred after the booster injection. Antibodies to mestranol crossreacted more than 100 percent with ethynylestradiol and to a small extent with norethindrone and norgestrel.

Animals↗

Radioimmunoassay of 15alpha-hydroxyestriol (estetrol) in pregnancy serum.

A more specific antisera against 15alpha-hydroxyestriol (estetrol) was produced in rabbits by immunization with 6-oxoestetrol-6-carboxy-methyloximino-bovine serum albumin. The synthesis of estetrol tetraacetate was greatly improved. Characterization of estetrol antisera revealed that it is more specific than those formerly obtained. A simple method of extraction of estetrol with alcohol from serum with high recovery is described. A radioimmunoassay method for pregnancy serum is characterized in regard to its specificity, accuracy, sensitivity and precision. The method is able to measure as little as 50 pg/tube or 167 pg/ml of serum. The intraassay coefficient of variation is 7.8% and that for interassay including personnel variation is 14.2%. Accuracy of the method, as determined by the recovery of non-radioactive estetrol (1 ng/ml) added to non-pregnancy serum, is found to be 89 +/- 8 (SD)%, CV = 8.7%, without correction for experimental losses. One hundred twelve pregnancy sera were analysed; the values obtained from normal subjects in the third trimester ranged from 240-950 pg/ml. The values obtained by this method are somewhat lower than those reported previously, presumably due to the higher specificity of the antibody.

Chemical Phenomena↗

Distribution of serum selenium, copper, and zinc in normal human pregnancy.

The distribution of the serum levels of selenium, zinc, and copper in human pregnancy at various gestational ages were determined from two ethnically and geographically different populations (Rosebud Indian Reservation and southeastern South Dakota) of 410 normal subjects. As gestation age increased, there was a significant increase and a slight decrease in the mean levels of copper and zinc, respectively. No change in the levels of selenium was observed. Significantly higher levels of both pregnancy and non-pregnancy serum copper were observed in the Rosebud population compared to that in southeastern South Dakota, possibly due to the significantly higher level of copper in the Rosebud water. No differences were observed in the zinc or selenium levels between the two populations. Serial measurements of these trace metals during the third trimester of pregnancy were performed on 18 subjects, and supported the trends described for copper and selenium. No decrease in zinc was observed in the individual subjects.

Copper↗

Essential role of nitric oxide and interferon-gamma for tumor immunotherapy with interleukin-10.

Several laboratories have reported anti-tumor activity for high levels of interleukin-10 (IL-10) expressed as a transgene or administered as recombinant protein. The authors have reported a positive correlation for nitric oxide production and anti-tumor activity of IL-10 in a murine model of breast cancer. In the current study, they sought evidence of a mechanistic role for nitric oxide in IL-10-mediated tumor growth inhibition. They wanted to determine whether pharmacologic inhibition of nitric oxide synthase (NOS) activity reverses the therapeutic effect of IL-10. Administration of either of two NOS inhibitors, aminoguanidine (AG) or L-lysine,N6-1-iminoethyl-dihydrochloride, appears to abrogate in part the tumor growth inhibition observed when IL-10 is overexpressed as a transgene in two murine mammary tumor cell lines. Nitric oxide levels were assessed at the tumor site by measuring nitrosylated heme levels by electron spin resonance spectroscopy. Nitric oxide hemoglobin levels were lower in tumors from aminoguanidine-treated mice, indicating that effective inhibition of nitric oxide production occurred at the tumor site. Previous investigations showed that the inducible form of NOS protein (iNOS), but not constitutive NOS, was expressed at higher levels in IL-10-expressing tumors. Because iNOS is regulated at the transcriptional level, the authors compared iNOS mRNA levels in IL-10 and control tumors. Northern analysis revealed strong iNOS message expression in all six IL-10-expressing tumors examined, whereas message was faintly detected in parental or 66-neo tumors. The inducible form of NOS is responsive to induction by interferon-gamma (IFN-gamma). The role of IFN-gamma in IL-10-mediated tumor inhibition and iNOS mRNA induction was determined. When tumors were transplanted to IFN-gamma mutant mice, the tumor-inhibitory activity of IL-10 was lost. Furthermore, iNOS mRNA was no longer induced in the absence of host expression of IFN-gamma. These data indicate that nitric oxide contributes to the anti-tumor activity of IL-10 and that expression of iNOS in this context depends on IFN-gamma.

Animals↗

Expression of the chemokines IP-10 and Mig in IL-10 transduced tumors.

Several laboratories have reported marked tumor inhibition when the cytokine interleukin-10 (IL-10) is overexpressed as a transgene in a variety of tumor cells. To identify critical effector molecules, we compared the expression of the chemokine crg-2, the murine homolog of human inducible protein 10 (human IP-10) in murine mammary tumors derived from the transplantation of six IL-10 expressing clones of tumor cell line 66.1, parental 66.1, or 66-neo-cells. We observed increased levels of IP-10 mRNA in all IL-10-expressing tumors examined in comparison to 66-neo. IP-10 mRNA was not detected in parental 66.1 tumors. The closely related chemokine Mig (monokine induced by interferon-gamma [IFN-gamma]) was also induced in all IL-10-expressing tumors. Studies of cultured tumor cells in vitro show that mammary epithelial tumor cells, in the absence of host elements, can express IP-10 and Mig in response to induction with either lipopolysaccharide (LPS) or IFN-gamma alone. The combination of LPS plus IFN-gamma resulted in even greater induction of IP-10 RNA. The kinetics of induction differ somewhat for the two chemokines, with IP-10 showing slower induction and less rapid decline. Because both Mig and IP-10 are chemotactic for tumor-infiltrating lymphocytes, we examined the presence of CD4+ and CD8+ lymphocytes in these tumors. Consistent with the upregulation of Mig and IP-10, we saw significantly increased numbers of CD8+ cells and a lesser increase in CD4+ cells in tumors with elevated levels of both chemokines.

Animals↗

Individualized cosinor assessment of circadian hormonal variation in third trimester human pregnancy.

Two clinically healthy pregnant women were studied in a single 24-h span during the third trimester. Blood drawn every 20 min was assayed for cortisol (F), dehydroepiandrosterone sulfate (DHEA-S), estriol (E3), and prolactin (PRL). Blood drawn hourly was assayed for progesterone (P), human placental lactogen (HPL) and 15alpha-hydroxyestriol (E4). Breast temperature (BT) was continuously monitored. Single cosinor analysis demonstrated statistically significant circadian rhythms for plasma concentrations of F, DHEA-S, and BT for both subjects, and of E3 for one subject. Statistically significant circadian rhythms in plasma concentrations of P, HPL, E4 or PRL could not be demonstrated in our third trimester subjects. However, analysis of data from subjects sampled at earlier gestational ages revealed highly significant PRL circadian rhythms. These results suggest that plasma concentrations of PRL show a progressive decrease in circadian amplitude despite a progressive increase in mesor with advancing gestational age. Frequent sampling and cosinor data analysis permit identification of circadian rhythms in BT. The use of BT as a potential marker for rhythms in plasma concentration of certain hormones awaits further scrutiny. The demonstration of several circadian endocrine rhythms in individual subjects in the third trimester of human pregnancy facilitates the usefulness of such marker rhythms.

Body Temperature↗