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Biomedical subjects

S Rao

Publications and source records attributed to S Rao.

At least 19 recordsLinked to original sources

Direct photoaffinity labeling of tubulin with taxol.

BACKGROUND: Taxol is a potent inhibitor of the replication of eukaryotic cells and has significant antitumor activity in human malignancies. The drug induces the formation of bundles of stable microtubules and blocks cells in the mitotic phase of the cell cycle. In vitro, taxol enhances the polymerization of tubulin to microtubules that are resistant to depolymerization. Although it is evident that taxol interacts with the tubulin-microtubule system, no information has been available on the binding site for the drug on the microtubule. PURPOSE: Our purpose was to determine if taxol binds to one or both of the tubulin subunits. METHODS: In the absence of a photoaffinity-labeled analogue of taxol, [3H]taxol was used directly to photolabel tubulin. A complex of microtubule protein and [3H]taxol was irradiated by ultraviolet light and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. RESULTS AND CONCLUSIONS: The radiolabeled drug preferentially binds covalently to the beta-subunit of tubulin, and the binding can be competed with unlabeled taxol. IMPLICATIONS: This observation is the first step in a study to determine the binding site for taxol on the microtubule.

Affinity Labels

Climate and admissions for mania in the tropics.

Seasonality of admissions for mania has been commonly reported. Most reports are from temperature zones. We analyzed admissions for mania covering a 9 year period and looked for any seasonal trends using existing methods. No seasonal variation was found. The hospital lies in the tropical zone with a relatively constant climate. This may influence the seasonal pattern of relapses in affective disorder.

Adult

Metastatic malignancy of the cervical spine. A nonoperative history.

Of 48 patients with spinal metastases treated at the Kenneth J. Norris Cancer Center at The University of Southern California Medical Center in Los Angeles, California between 1984 and 1987, 19 consecutive patients with cervical metastatic disease were identified and followed until death or remission. Prostate, breast, and lung neoplasms accounted for 57% of the cervical metastases. Associated nonspinal skeletal, extraskeletal, or multiple-level spinal metastases were seen in 95% of patients. Mean time from diagnosis of primary tumor to cervical metastasis was 29 months and mean survival after that was 14.7 months. Pain was the initial symptom in 89% of cases. No patient had neurologic deficit and three (16%) had slight radiographic collapse and deformity. Only one (5%) patient had documented instability. All patients had nonoperative treatment with radiotherapy, chemotherapy, or a combination. Irrespective, the pain recurred in all patients by 6 months. Nonoperative treatment may be appropriate in the absence of significant neurologic deficit or instability. The return of symptoms by 6 months warrants alternative modes of therapy.

Breast Neoplasms

Radiotherapy and verrucous carcinoma of the oral cavity. A study of 107 cases.

One hundred and seven cases of oral verrucous carcinoma treated primarily with radiotherapy at Kasturba Hospital, Manipal, India between 1977 and 1987 were analysed concerning location within the oral cavity, clinical extent, and effectiveness of radiotherapy. The most common site was the buccal mucosa followed by the buccogingival sulcus. Only 13.2% of the patients presented with T1 or T2 tumours and 32.7% had clinically negative nodes. Biopsy had to be repeated more than once in 22 patients to get confirmation of invasive carcinoma. The 5-year survival rate was 35% for stage III and 26% for stage IV. The treatment results with radiotherapy were comparable with those for ordinary squamous cell carcinoma of the oral cavity. It is felt that the treatment policy for verrucous carcinoma can be the same as for ordinary squamous cell carcinoma. In order to prevent delay in diagnosis and treatment, proper cooperation between the treating oncologist and the pathologist is essential.

Adult

Breastfeeding and weaning practices in relation to nutritional status of infants.

During the critical period of infancy, breastfeeding and weaning practices play an important role in determining the growth of an infant. The present study investigates the issue by observing 225 infants from Low Socio Economic (LSE) class (n = 150) and High Socio Economic (HSE) class (n = 75) for weight, height, and feeding practices. Almost all artificially fed (AF) infants in LSE class were malnourished while this was not so in the HSE class. However, the proportion of malnourished children in the LSE class for partially breastfed (BF + AF) group was comparable with exclusively breastfed (BF) group and was significantly lower (p < 0.01) than AF group indicating protective effect of partial breastfeeding against risks of contamination associated with weaning foods in such communities: The real bottleneck thus appears to be the lack of knowledge of handling and giving weaning foods in adequate quantities. Educating mothers appears to be the meaningful solution for improving the nutritional status of infants in poor communities.

Breast Feeding

Blood viscosity parameter correlation with types of leukemia.

We investigated the hemorheological, hematological and biochemical parameters in 30 cases of acute lymphocytic leukemia (ALL), 21 cases of acute myelogenous leukemia (AML) and 30 cases of chronic myelogenous leukemia (CML). The parameters studied include whole blood viscosity, plasma viscosity, erythrocyte sedimentation rate (ESR), red cell filterability, hematocrit, platelet count and aggregation, fibrinogen, hemoglobin, leucocyte count, bleeding time and lactate dehydrogenase activity (LDH). In the cases of ALL we observed significant decrease in whole blood viscosity, hemoglobin, hematocrit and platelet count but an increase in plasma viscosity, fibrinogen, bleeding time and LDH activity. In the cases of AML, we observed increase in whole blood viscosity, plasma viscosity, ESR, fibrinogen, leucocyte count, bleeding time and LDH activity but decrease in the hemoglobin, hematocrit and platelet count. In the cases of CML, we observed an increase of whole blood viscosity, plasma viscosity, ESR, fibrinogen elevation but decreases in bleeding time. In all cases, red cell filterability was unaffected.

Blood Sedimentation

Carcinoma of the ampulla of vater after curative treatment for Hodgkin's disease.

A 43-yr-old woman developed carcinoma of the ampulla of Vater 20 yr after being successfully treated for Hodgkin's disease with radiotherapy and chemotherapy. Conditions related to the chronic effect of radiation, such as narrowing and fibrosis of abdominal tissue, hampered her diagnosis and treatment. After a total pancreatectomy to remove the carcinoma, the patient recovered. However, 15 months later, she developed severe digestive disturbances, adrenal insufficiency, pulmonary emboli, and vasculitis. She died the next month of sepsis and adult respiratory distress syndrome. Although her complications probably were related to residual effects from therapy and surgery, she had no clinical evidence of tumor recurrence.

Adenocarcinoma, Papillary

Population-derived comparisons of ambulatory and office blood pressures. Implications for the determination of usual blood pressure and the concept of white coat hypertension.

BACKGROUND: Ambulatory blood pressures (BPs) have generally been reported to be lower than office blood pressures, but population-based data are lacking. METHODS: To better characterize ambulatory and office BP relationships, we explored the interrelationships of BPs measured in the office by mercury sphygmomanometry, 24-hour ambulatory BP measured with a portable device, and echocardiographic left ventricular mass in a random sample of 50 men aged 51 to 72 years drawn from a much larger pool. Office BP was based on the mean of 10 measurements performed over five visits. RESULTS: Among all participants, mean 24-hour ambulatory and mean office BPs were highly correlated: r (systolic/diastolic) = .90/.79; and both mean 24-hour and mean awake ambulatory BPs were significantly higher than mean office BPs. For the subsample not receiving antihypertensive therapy, mean ambulatory and office BPs were similar in terms of their associations with Penn left ventricular mass index (LVMI). No association between BP and left ventricular mass was observed among the subjects receiving antihypertensive medication. CONCLUSIONS: We conclude that a single session of 24-hour ambulatory BP monitoring is unlikely to improve the determination of usual BP in older white men beyond that achievable with BP carefully measured over five separate office visits; and that white coat hypertension is rare in this population.

Aged

Prolonged breast-feeding and malnutrition among rural Indian children below 3 years of age.

Long periods of exclusive as well as partial breast-feeding in poor communities are of considerable importance from a nutritional standpoint, as it is in these communities that malnutrition is predominant. Although benefits of exclusive breast feeding have been well documented, those for partial breast-feeding have not been examined. The present study in particular examines the effects of prolonged breast-feeding, i.e. exclusive breast-feeding beyond 6 months or partial breast-feeding up to 2-3 years, in terms of prevalent malnutrition and morbidity among rural children. A total of 395 children were observed for weight, height, information on duration of breast-feeding, age at weaning and morbidity in terms of recent illness in the 7 days prior to the day of visit. Exclusive breast-feeding beyond 6 months and up to 12 months appeared beneficial in terms of reduced morbidity. Beyond infancy, there was no evidence of any protective effect of partial breast-feeding. This could be due to poor lactational performance of mothers and their unawareness about it resulting in inadequate weaning foods being offered to partially breast-fed children. Significant differences in male and female children in the extent of malnutrition pointed towards discrimination against girls even in respect of exclusive breast-feeding. The study highlights the need for advocating proper weaning practices while recommending prolonged breast-feeding in poor communities.

Age Factors

Importance of periodic measurements in evaluating feeding programmes.

Attempts were made to show that periodic measurements are important for evaluating impact of feeding programmes as considerable "within variation" in increments exists which cannot be overlooked. From two socio-economic classes two kindergartens were selected one of which was implementing a feeding programme while the other was not. A total of 273 children were measured for weight and height, three times during the period of 7 months. Normal children showed significant gain in weight while malnourished children showed significant gain in height. The significance in weight (or height) increment at the end of the feeding programme did not necessarily mean that the significance could be obtained in each period even of equal time interval. Simple and cross correlations in increment revealed that weight increment in one period was significantly associated with height increment in the following period suggesting alternating priorities of the body for growth. Carefully planned longitudinal growth studies are therefore necessary for better understanding of growth process and thereby for proper evaluation of feeding programmes.

Body Height

Cell-cycle-dependent, differential prenylation of proteins.

Isoprenylated proteins related to cell growth have been detected during proliferation. Since cholesterogenesis (isoprenoid synthesis) is mandatory for cell proliferation, the observation of a temporally coordinated protein prenylation during the cell division cycle might constitute obligatory processes in the signalling pathway for initiating DNA replication and/or in maintaining the growing state. We have found such a definitive cell-cycle-phase-dependent pattern of prenylation for various classes of cytosolic and nuclear matrix proteins in synchronized HepG2 cells. Characteristic [3H]mevalonate incorporation began to increase during mid-to-late G1, just after cholesterol synthesis reached its apex, and peaked just prior to or coincident with mid S. Incorporation then declined subsequent to S (during G2) as cells approached mitosis. Prior to the rise in mevalonate incorporation into proteins, during early-to-mid G1, steady-state [14C]acetate incorporation into chromatographically resolved cholesterogenic lipid intermediates displayed a maximum only into cholesterol. However, during the late-G1/S interval, a singular peak of 14C incorporation was found for the farnesyl moiety (farnesol/nerolidol plus farnesyl diphosphate). Except for the farnesyl moiety, none of the other polyisoprenoids detected by our procedures showed any fluctuation in 14C incorporation subsequent to mid G1. These results support the proposal that subsequent to peak cholesterol synthesis in early-to-mid G1, the generation of a cholesterol-pathway-dependent set of post-translationally modified, polyisoprenylated proteins could constitute an obligatory step leading to the duplication of the cellular genome, thereby impelling transit through the cell cycle. The well known high flux through cholesterogenesis in tumors, which manifests an intrinsic lack of sensitivity to feedback inhibition and operates continuously, is consonant with this proposal.

Alkylation

Automatic memory processes in patients with multiple sclerosis.

To better understand the nature of the memory deficit in patients with multiple sclerosis, we designed a study to compare automatic vs effortful memory processes. Forty-one patients with definite multiple sclerosis and 45 demographically matched normal control subjects were administered two tasks designed to assess both automatic (monitoring frequency and modality) and effortful (free and cued-recall) processing. Results indicated that patients with multiple sclerosis, as expected, were significantly impaired on memory measures requiring effort, but performed normally on automatic measures. Performance on the memory indexes did not correlate with self-reported depression. The implications of these findings for delineating the locus of the memory impairment in multiple sclerosis is discussed.

Adult