Biomedical subjects
Publications and source records attributed to V L Kumar.
Steroids produce anaesthesia besides producing the well known metabolic and hormonal effects. A number of anaesthetic steroids have been synthesized and tried clinically. Hydroxydione, althesin, minaxolone and pregnanolone are among those studied in detail. They act through GABAergic mechanism and are known to be advantageous over barbiturates.
Explore the source record for details and available documents.
Cytosolic and nuclear androgen, estrogen and progesterone receptor content was measured in the groups of 11 prostatic carcinoma (PCA) and 32 benign prostatic hypertrophy (BPH) samples. All BPH cases were positive for the cytosolic progesterone (PRc) and estrogen receptor (ERc), whereas only 85% of cases (23/27) contained the androgen receptor (ARc). Only those five patients who received estrogen treatment in the PCA group had detectable ARc. PRc was present in all of the PCA cases, whereas ERc could be detected in only 82% (9/11) of cases. Cytosolic contents of all three steroid receptors, however, were higher in the PCA group. The level of nuclear steroid receptors, although present in fewer cases in both groups, was higher than the cytoplasmic receptors. The serum profile of estradiol, cortisol, and prolactin was normal in both groups, whereas LH, FSH, and progesterone levels were higher than in normal adults. Serum testosterone level was within normal range in the BPH group, but it was significantly below normal (P less than 0.005) in PCA patients.
The methylation of the human oestrogen receptor (ER) gene was analysed by restriction enzymes in normal and neoplastic human breast tissues and cell lines. CCGG sequences in regions inside the gene, which are methylated both in normal breast and in tissues that are not the target of the oestrogen, are hypomethylated in 30% of tumours, both ER+ and ER- carcinomas. Moreover, 5' sequences of the gene, which are hypomethylated in normal breast and not in tissues not the target of oestrogen, are methylated to a lower degree in ER+ carcinomas, whereas they are methylated to a greater degree in ER- carcinomas. However, the same region is equally hypomethylated in both ER+ and ER- cancer cell lines. Our results indicate that in breast carcinomas ER DNA methylation is deranged, and in cancer cell lines is different from that observed in primary tumours. Furthermore, the abnormal methylation in the 5' end seems to be related to abnormal expression, namely diffuse hypomethylation in carcinomas with high ER content and hypermethylation in carcinomas without ER. These findings support our previous hypothesis that DNA methylation could be involved in the control of ER gene expression and demonstrate that abnormal ER gene methylation is a typical feature of breast cancers.
Demethylation of specific sites or restricted genomic regions has been reported to correlate with gene activation and also with carcinogenesis. As abnormal expression of Estrogen Receptor (ER) could be involved in the genesis or progression of tumors in estrogen target tissues, the methylation of ER gene has been compared in 8 endometrial carcinomas and 29 normal endometria. In order to look for a correlation between methylation and expression, levels of ER RNA were also measured. While the 5' region of ER gene was found to be demethylated in both normal and carcinomatous tissues, there was demethylation of some specific sites in the internal part of the gene only in the carcinomas examined. In addition, in the carcinomatous tissues the levels of ER RNA were low, indicating that an increase of ER gene hypomethylation does not raise, and even may reduce, the ER expression in endometrium. The abnormal undermethylation observed in ER gene appears to be unrelated to general DNA hypomethylation which is frequently present in neoplastic tissues; nor has it been found in ER DNA isolated from breast carcinomas. These data strongly support the hypothesis that such a methylation is specifically related to endometrial transformation and therefore it can be considered an additional marker of this disease.
Estrogen Receptor (ER) RNA has been studied in ER positive and ER negative cells, grown in alpha medium and fetal calf serum (FCS), with and without estrogen addition. ER mRNA was detected only in ER positive cells. When cells were grown without estrogen addition, a progressive and transient increase of ER RNA levels was observed. When cells were cultured with estradiol, the ER RNA increase took place early and ER RNA levels remained 2 times higher than in untreated cells. Therefore, a down-regulation of ER RNA is not apparent in neoplastic breast cells. We hypothesize that the increase of ER expression is caused by stabilization of ER transcripts, due to the estrogen induced ER cytoplasmic depletion.
Latex of Calotropis procera was studied for its inflammatory reactions using pedal oedema and air pouch models of inflammation in rats. Subcutaneous injection of aqueous solution (0.1 ml of 1%) of dry latex (DL) into the plantar surface of paw produced significant inflammation. Maximum inflammatory response was obtained 1 h after the injection and was maintained for a further 1 h. The inflammatory response was accompanied by an increase in vascular permeability that reached its maximum within 15 min. Inflammation was also induced in the 6-day-old rat air pouch by injecting a 2.5% solution of DL. The latter model was characterized for the exudate volume and its protein concentration, and wet and dry weights of granuloma. A time-course study indicated that both the exudate volume and the weight of granuloma were at maximum on day 5 after DL injection while the protein concentration peaked on the third day. Further, the two models were also studied for the anti-inflammatory effect of various drugs. It was observed that in the pedal oedema model, phenylbutazone was more effective than prednisolone while almost complete inhibition was produced by mepyramine and cyproheptadine. On the other hand, in the air pouch model, prednisolone was more effective than phenylbutazone in inhibiting the inflammation. Thus, the DL-induced inflammation in different models could be used to evaluate anti-inflammatory drugs.
Gene therapy replaces or supplements the activity of a resident defective or missing gene by a cloned functional one. A functional gene may be delivered to the target tissues ex vivo or in vivo using various physical methods and several chemical and biological vehicles. In this article we present an overview of different experimental models and the progress made in clinical studies on gene therapy and discuss the prospects of the antisense approach and the ethical concerns related to the technique.
Explore the source record for details and available documents.