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Biomedical subjects

R Seshadri

Publications and source records attributed to R Seshadri.

At least 145 records · Page 8Linked to original sources

Enumeration of thioguanine-resistant lymphocytes using autoradiography.

Strauss and Albertini (1979) proposed a method whereby the frequency of thioguanine-resistant lymphocytes could be measured by an autoradiographic technique and suggested that it would provide a measure of in vivo mutation frequency. A number of variables influencing the method were studied and concentration of thioguanine and duration of assay found to be particularly important. The modified method finally arrived at involved culture of PHA-stimulated lymphocytes for 64 h in the presence of 40 microgram/ml of thioguanine, lysis of cells with Nonidet and collection of nuclei on Nucleopore membranes. The frequency of TG-resistant cells was 1.5 x 10(-6) - 1.7 x 10(-5) in young adults and it showed an increase with age. The technique was also adapted for use with continuously cultured lymphocytes, by using a concentration of 60 microgram/ml of thioguanine and an incubation time of 72 h. The frequency of TG-resistant continuously cultured cells was less than 10(-6) - 2 x 10(-5). Consideration of the effect of different variables on the assay suggested that the above estimates for TG-resistant lymphocytes were more valid than the previously published substantially higher estimates.

Autoradiography↗

Effect of age on sensitivity of human lymphocytes to radiation. A brief note.

Survival of human lymphocytes after X-ray and ultraviolet irradiation was studied in individuals of various ages using a technique of cloning in soft agar. There was no effect of age on survival after ultraviolet irradiation but lymphocytes from elderly individuals were approximately twice as sensitive to X-radiation as lymphocytes from young individuals. The results are relevant to the possible importance of DNA damage and repair in cellular ageing.

Adolescent↗

Sister-chromatid exchange (SCE) analysis in mothers exposed to DNA-damaging agents and their newborn infants.

The incidence of SCE in the lymphocytes of mothers and their newborn infants was determined. A detailed antenatal history of parental habits such as smoking, alcohol consumption and possible exposure to DNA-damaging agents was documented. The results showed that the SCE rate in the newborn is significantly less than that of their mothers. Mothers who consumed alcohol, but not cigarette smokers, had a significantly increased SCE rate compared to control mothers. However, these maternal habits did not affect the SCE rate of their infants. Neonates with neural tube defects showed a significantly increased SCE rate compared to normal babies.

Abnormalities, Multiple↗

Sister chromatid exchange in aplastic anemia.

The incidence of sister chromatid exchanges (SCE) in the lymphocytes of patients with aplastic anemia (AA) was determined before and after exposure to mitomycin C (MMC). The "baseline" SCE rate was significantly higher in AA, but MMC-induced SCE rate was not different compared to controls. It is suggested that some patients with AA may have an underlying DNA damage.

Adolescent↗

Oestradiol and progesterone receptors in the mammary tissue and tumours of female Holtzman rats following 7,12-dimethylbenz(a)anthracene administration.

A single dose of the carcinogen 7,12-dimethylbenz(a)-anthracene (DMBA) when administered to 55-day-old female Holtzman rats did not produce any change in the pattern or amount of oestradiol receptors in the breast tissues, when compared to age-matched control animals. The period of observation extended up to 280 days of age. Following DMBA administration to 102 animals, only 60% developed carcinomas of the breast, of which 59 and 50% were ER- an PgR-positive, respectively. This lower yield of steroid receptor-positive tumours in this strain of rats was also reflected in a very low incidence of regression of tumours to ovariectomy. Plausible explanations for both these findings have been offered.

9,10-Dimethyl-1,2-benzanthracene↗

Chronic myeloid leukemia. A possible new variant in a child.

A case of Philadelphia (Ph') chromosome negative chronic myeloid leukemia (CML) in a child is reported. The age of onset (7 years) and duration of survival (40 months) are not typical of juvenile CML and the relatively low leukocyte and hemoglobin F concentrations are more akin to the findings in Ph' negative CML in adults. There was refractoriness to chemotherapy with the exception of a dramatic response to a combination of prednisone and vincristine, despite the absence of terminal transferase activity in circulating blood cells. Splenic irradiation, splenectomy, and leukapheresis were ineffective. Transition to a terminal aggressive phase caused a marked change in the growth characteristics of peripheral blood cells in vitro. This patient may represent a new variant in the spectrum of childhood CML.

Child↗

Hormone dependency of rat mammary carcinoma--a comparison of two assay systems.

Succinic dehydrogenase activity of the DMBA induced tumor explants cultured with or without hormones was assessed histochemically while receptors for estrogen (ER) and progesterone (PgR) were estimated from the cytosol fraction of the tumor tissue. Tumor regression following ovariectomy (OVX) was kept as the end point for determining hormone dependency. By in vitro method positive correlation was observed in 5 of 6 responsive or hormone dependent tumors, and 13 out of 14 independent tumors. Presence of receptors (ER + PgR, PgR) correlated with responsiveness in 4 of 6 tumors while their absence in the non-responsive group correlated in 6 of 14 tumors. Prolactin responsive tumors did not regress following OVX even if ER + PgR or ER/PgR were present. Using the same tumor tissue the results of hormone dependency by the two methods were identical in only 9 of 20 tumors.

9,10-Dimethyl-1,2-benzanthracene↗

Is aplastic anaemia due to abnormality of D.N.A.?

Lymphocytes from eleven patients with aplastic anaemia were cultured with various agents which interact with D.N.A., and the proliferative responses to phytohaemagglutinin were measured. Lymphocytes from seven of the eleven patients were unduly sensitive to bleomycin, an agent causing strand breaks in D.N.A. The findings suggest that D.N.A. in these seven patients was abnormal, possibly as a result of an abnormality of D.N.A. repair. It is suggested that in aplastic anaemia D.N.A. damage in stem cells may lead to a failure of proliferation.

Adolescent↗

Oestradiol receptors and histogenesis in normal female breast of Holtzman rat.

This paper embodies observations on the specific oestrogen receptor concentrations and histogenesis in the breast tissues of female Holtzman rat from day 10 of birth to day 260. It is noted that up to day 60, even though the normal differentiation and morphological growth of mammary tissue is in progress, oestradiol receptors are not detected. On the contrary, during this period maximum receptor concentrations have been observed in another target tissue viz. uterus. After day 60, it is the uterus which shows minimal amounts of receptors, while the breast tissue has appreciable amounts of receptor proteins. During this period, the morphological growth of the breast is maximum and this ceases apparently by day 90. Repeated estimations fail to reveal any receptors between days 73 to 87 and this phenomenon cannot be explained at present. Similarly from day 140 onwards no oestradiol receptors are evident. This probably is the cut off point for the receptors in the normal rat breast tissue.

Aging↗