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Biomedical subjects

S Reddy

Publications and source records attributed to S Reddy.

At least 235 records · Page 13Linked to original sources
PubMed1990

Haematological studies on pre-menopausal Indian and Caucasian vegetarians compared with Caucasian omnivores.

Full blood counts, serum ferritin, vitamin B12 and folate, erythrocyte folate concentrations and nutrient intakes were estimated in twenty-three Indian vegetarian, twenty-two Caucasian omnivores and eighteen Caucasian vegetarian women aged 25-40 years. Energy and copper intakes were lower in the Indian women than in the Caucasians. Intakes of dietary fibre, vitamin C and folate were greater and the proportion of energy derived from fat was lower in the vegetarians than in the omnivores. Vitamin B12 and protein intakes were lower in both vegetarian groups than in the omnivores. Fe intake was similar in all the groups but haem Fe provided one-quarter of the Fe intake of the omnivores. Haemoglobin concentrations were generally inside the normal range in all groups, but were lower in the Indians as were mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH). Higher MCV, MCH and lower erythrocyte (RBC) counts were observed in Caucasian vegetarians compared with the Caucasian omnivores. In both groups of vegetarians, concentrations of serum vitamin B12 and ferritin were markedly lower than in the omnivores. RBC folate concentrations were lower in the Indians than in either of the Caucasian groups when subjects taking supplements were excluded. It is concluded that vegetarians need to ensure they have adequate intakes of Fe and vitamin B12.

Adult↗
PubMed1990

Change in circulating cyclo(His-Pro) concentrations in rats after ingestion of oral glucose compared to intravenous glucose and controls.

Changes in circulating cyclo(His-Pro) (CHP) levels after ingestion of 0.5 g/kg of glucose (oral) were measured in 32 Sprague Dawley rats at varying time points between 0 (before glucose) and 60 minutes. Each rat provided one time point. CHP levels displayed a biphasic response rising from 933 +/- 56 pg/ml to 1083 +/- 287 pg/ml (p greater than 0.05), followed by a fall to 543 +/- 46 pg/ml (p = 0.002) and then a recovery to near baseline values. To further investigate this response, a separate group of rats were sampled sequentially after 3 g/kg oral glucose (n = 7), 0.6 g/kg I.V. glucose (n = 6) or controls given saline only (n = 14). CHP levels were significantly elevated in the oral glucose group at 5 (p = 0.048) and 12 (p = 0.02) minutes compared to controls, while the i.v. glucose group was not statistically different from controls. Comparison of the mean of the highest incremental response to baseline values in each group revealed a greater excursion in CHP levels after oral (p = 0.027) glucose than after I.V. (p = 0.08) glucose. These data suggest CHP is acutely and reversibly elevated after glucose ingestion in rats and that the response is greater after oral glucose than after i.v. glucose.

Administration, Oral↗
PubMed1990

Longitudinal study of islet cell antibodies and insulin autoantibodies and development of diabetes in non-obese diabetic (NOD) mice.

We have previously shown the presence of circulating islet cell cytoplasmic antibodies (ICA) and insulin autoantibodies (IAA) in the NOD mouse before onset of insulin-dependent diabetes mellitus (IDDM). Here we have determined the levels of the two autoantibodies in 28 female NOD mice longitudinally from approximately day 40 to day 250, to examine their ontogeny, association and predictive value for diabetes. All animals (11 diabetic, 17 non-diabetic) showed varying levels of ICA at some stage, while IAA activity was found in 21 out of 28 mice. Expression of both the markers was seen in more than half of the animals by day 60, with higher levels and rates occurring subsequently in both diabetic and non-diabetic groups. The expression of ICA did not always correlate with that of IAA. There was no apparent difference in the ontogeny of ICA and IAA between the two groups. During the study period the number of animals with ICA was similar in the two groups, while the number of those with IAA was higher in the diabetic animals. In this group declining and rising levels of ICA were seen just before clinical diabetes with frequent peaks of IAA. In the same animals, eight out of 11 mice showed co-expression of high levels of both markers either intermittently or persistently prior to onset, whereas only one non-diabetic animal showed this. We conclude that the ontogeny and serum level of ICA or IAA alone could not be used to predict the clinical onset of diabetes in these animals. However, co-expression of high levels of both markers prior to onset may suggest a strong predisposition to clinical diabetes. This may have relevance to attempts to predict the onset of IDDM in humans who have one or both of these immunological markers.

Animals↗
PubMed1990

Sequence and functional differences between Schmidt-Ruppin D and Schmidt-Ruppin A strains of pp60v-src.

We show that Schmidt-Ruppin D pp60v-src kinase activity is reduced by a mutation previously shown to be associated with Schmidt-Ruppin A pp60v-src temperature sensitivity and that its reduced transforming activity is associated with a conformational change in the SH3 region. The evolutionary relationship of seven v-src strains was studied by using parsimony analysis.

Amino Acid Sequence↗
PubMed1990

Differential Na fluxes with artificial and native fluids in clip models of volume expansion.

Earlier we demonstrated significant differences in proximal tubular Na transport inhibition during saline volume expansion (VE) depending on whether artificial (AF) or native harvested tubular fluid (HTF) was used. In the present experiments the shrinking-drop technique was used to measure volume flux (Jv) in the early- and late-clip models of VE with AF alternating with HTF. In early-clip rats, with AF, Jv (x 10(4) mm3.mm-2.s-1) during the nonexpanded period was 2.92 +/- 0.105; during subsequent VE, it was 2.20 +/- 0.180 and 1.97 +/- 0.149 with HTF (for the latter two P greater than 0.3). In late-clip rats they were 2.83 +/- 0.135, 1.99 +/- 0.157, and 1.50 +/- 0.171 (for the latter two P less than 0.001), respectively. With AF, transport was inhibited equally in both models during VE. There were no significant differences in the electrolyte composition of AF and HTF during shrinkage as measured by microprobe analysis. The 47% inhibition of Jv with HTF but not AF during VE in the late-clip but not the early-clip rats strongly implies the presence of factors other than physical forces during VE, which inhibit proximal tubular Na transport. Studies of tubular transport during VE need to be performed using both AF and HTF.

Animals↗
PubMed1990

Concurrent chemotherapy and thoracic irradiation in non-small cell lung cancer.

Do results from recently reported phase II trials of combination chemotherapy and concurrent radiation warrant evaluation in a randomized study? Our bias is that only treatment regimens associated with a twofold increase in median survival should be considered for a phase III trial increase in median survival. Therefore, for stage IIIA N2 NSCLC patients median survival should increase from 12 to 24 months, and for stage IIIB patients, it should increase from 9 to 18 months. Although survival results from some combined modality trials are encouraging, thus far no concurrent chemotherapy-radiation regimen appears to have produced the preceding results.

Antineoplastic Agents↗
PubMed1990

Early nicotinamide treatment in the NOD mouse: effects on diabetes and insulitis suppression and autoantibody levels.

Nicotinamide, a vitamin B group substance, has previously been shown to prevent diabetes and suppress insulitis in the NOD mouse. In order to further understand its mode of action, we have administered the vitamin orally to female NOD mice from weaning and have examined its effect cross-sectionally (days 40, 106 and 250) on the severity of insulitis, changes in T cell subpopulations, levels of islet cell antibodies (ICA) and insulin autoantibodies (IAA) and diabetes development. At day 40, the incidence and severity of insulitis were much lower in the nicotinamide group (n = 22) than in the control mice (n = 21; 23.8% versus 57.1%, 2.9 +/- 1.4% versus 9.6 +/- 2.6%, respectively). At day 106, the incidence of insulitis increased to 82% in the nicotinamide group (n = 11) and remained similar at day 250 (n = 14). At these two age groups all control mice developed insulitis. The insulitis score increased to about 20% at day 106 in the nicotinamide mice and remained the same at day 250. In the control animals, this score increased from 9.6 +/- 2.6% at day 40 to about 33% and 60% at days 106 and 250, respectively. Diabetes was not detected in the 14 animals maintained on nicotinamide while 4/14 control mice developed the disease with severe insulitis. Most of the immune cells infiltrating the islets were T cells, with higher numbers of L3T4 than Lyt2 cells. At days 40 and 106, the L3T4:Lyt2 cell ratios remained unchanged in both the nicotinamide and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

In vitro uterine response to tetramethylpyrazine, the active constituent of chung chong (a traditional Chinese medicine).

Tetramethylpyrazine is extracted from Rhizoma ligustici wallichii, an herb used in the Chinese medicine Chung Chong. Both herb and extract have been used in the treatment of anginal pain and stroke. Animal studies in the West have shown that tetramethylpyrazine improves coronary blood flow, is short acting, and has a low toxicity. There are no clinical or animal studies on the uterine effects of tetramethylpyrazine. We present results of a preliminary study with isolated uterine strips from rats. We found that tetramethylpyrazine, in a dose-dependent manner (0.6 to 20 micrograms/ml), reduced uterine diastolic tone and inhibited the response to oxytocin (0.02 to 0.32 micrograms/ml). Higher concentrations of tetramethylpyrazine were needed to block the uterine responses to prostaglandin E2 (0.01 to 0.1 microgram/ml). On the basis of clinical and folk experience in the Far East, tetramethylpyrazine appears to have fewer systemic effects in human beings than have the beta-adrenergic agonists or calcium channel blockers. We suggest that studies in the whole animal and in the clinic might provide reasons to use tetramethylpyrazine to reduce uterine contractions and tone in pregnant women at term.

Animals↗
PubMed1989

Preoperative chemotherapy and irradiation for stage III non-small cell lung cancer.

Surgical therapy for stage III non-small cell lung cancer (NSCLC) has not resulted in substantial long-term survival. Neoadjuvant treatment programs that could down-stage the tumor and achieve increased long-term survival would be of obvious benefit. We have used preoperative simultaneous chemotherapy and irradiation in 85 patients with clinical stage III non-small cell lung cancer considered candidates for surgical resection. One group of 56 patients was treated with cisplatin, 5-fluorouracil, and simultaneous irradiation for five days every other week for a total of four cycles. After treatment, 39 patients underwent resection, and the operative mortality was 2 (5%) of 39. A second trial was undertaken in which etoposide (VP-16) was added because of its synergism with cisplatin. In this group, 29 patients were considered to have potentially resectable disease, and 23 underwent thoracotomy with 1 operative death (4%). Of the total of 62 patients having thoracotomy, 60 underwent resection (97%). Complications were major, and there were four bronchopleural fistulas. For the 85 patients eligible for surgical intervention in these two groups of patients, the Kaplan-Meier median survival estimate is 40% at 3 years. The median survival of the 62 patients having thoracotomy is 36.6 months. Combination preoperative chemotherapy and irradiation is feasible with acceptable toxicity and operative mortality in patients with clinical stage III non-small cell lung cancer. Prospective randomized studies are suggested for further evaluation of this treatment program.

Carcinoma, Non-Small-Cell Lung↗
PubMed1989

Whole-abdomen radiation therapy in ovarian carcinoma: its role as a salvage therapeutic modality.

A significant proportion of patients with epithelial ovarian carcinoma eventually fail after initial responses to chemotherapy. Further treatment with chemotherapy consisting of either the same combination or second-line regimens has been ineffective in producing durable responses. Thus, between June 1983 and June 1987, thirty patients with epithelial ovarian carcinoma who failed one or more chemotherapeutic regimens were treated with whole-abdominopelvic-cavity radiation therapy. Prior to the radiation the amount of residual disease after debulking was noted to be microscopic in 16 patients and macroscopic in 14 patients. Radiation was delivered with an open-field technique that extended from the domes of the diaphragm to the obturator foramina. Doses of 2500 cGy were planned to the whole abdomen, with a boost of another 2500 cGy to the pelvic and or paraaortic nodes when indicated. Higher doses were delivered to the areas of gross disease in the pelvis. Only 2 patients were unable to complete the planned therapy. Another 26% of the patients required interruption of the therapy secondary to hematologic toxicity but eventually completed the treatment. With an overall median follow-up of 14 months, 56% of the patients remain alive. Two-year actuarial survival and recurrence-free survival rates are 47 and 32%, respectively. The survival and recurrence-free survival rates for the group with microscopic residual disease--61 and 33%, respectively--are better than those for the patients with macroscopic residual disease--36 and 18%. The abdominopelvic cavity was the first site of failure in all but one of the 17 patients who have failed. In spite of the higher doses, pelvic failure alone or as a component occurred in 54% of the patients. Small bowel obstruction necessitating surgical intervention as a complication of therapy was seen in 13% of the patients.

Abdomen↗
PubMed1989

Stage I and II non-Hodgkin's lymphomas: long-term results of radiation therapy.

One hundred and sixteen patients with Stages I and II non-Hodgkin's lymphomas were treated with curative radiotherapy between 1964 and 1977. The initial biopsy material was classified according to the criteria of Rappaport et al. All the patients except six were followed for a minimum of 8 years or until death with ninety-two patients having been followed for 10 or more years. Histological pattern was found to be an important prognostic factor with better survival in patients with nodular histology. There were forty-three patients with an initial involvement of an extra-nodal site forming 37% of the total group. Stage I extra-nodal lymphomas had a survival and recurrence-free survival rates of 80% and 74% respectively, similar to those of nodal lymphomas. Stage II patients in both groups did worse than those with Stage I. Survival rates and disease-free survival rates for different histologic types and their pattern of recurrence are presented.

Follow-Up Studies↗
PubMed1988

The cellular src gene product regulates junctional cell-to-cell communication.

Overexpression of the cellular src gene in NIH 3T3 cells causes reduction of cell-to-cell transmission of molecules in the 400- to 700-dalton range. This down-regulation of gap junctional communication correlates with the activity of the gene product, the protein tyrosine kinase pp60c-src. The down-regulation was enhanced by point mutation of Tyr527 (a site that is phosphorylated in pp60c-src and that inhibits kinase activity) or by substitution of the viral-src for the cellular-src carboxyl-terminal coding region. Mutation of Tyr416 (a site phosphorylated upon Tyr527 mutation) suppresses both the down-regulation of communication by Tyr527 mutation and that by gene overexpression. The regulation of communication by src may be important in the control of embryonic development and cellular growth.

Animals↗
PubMed1988

Ontogenic development of peptide hormones in the mammalian fetal pancreas.

The ontogeny of insulin, glucagon, PP and somatostatin in the mammalian fetal pancreas has been examined in recent years largely by immunocytochemistry and in some instances by radioimmunoassay. Complete ontogenic data are available only for the rat, human, pig and sheep. Figure 3 compares the time of appearance of the endocrine cell-types within the fetal pancreas when the periods of gestation of the four species are converted to a uniform scale. The striking ontogenic difference in the rat probably reflects the immaturity of the rodent fetus at birth compared with the human, pig and sheep. In the fetal pancreas, differences in cell number of glucagon and PP cells in the dorsal and ventral lobes become apparent from an early gestational period. Factors responsible for the functional and structural maturation of the fetal pancreatic endocrine cells and the processes involved in pancreatic organogenesis are poorly understood. Studies in these areas would have clinical implications since it may be possible in the future to employ agents for selective replication of fetal beta-cells for transplantation in patients with Type I diabetes, bearing in mind that such cells must have the capacity to respond to normal stimuli and repressors when transplanted. The presence of the other islet cell-types may be obligatory for these appropriate responses. This would require a more complete knowledge of those factors which produce the normal selectivity of the four hormonal cell-types.

Animals↗
PubMed1988

Ontogeny of islet cell antibodies, insulin autoantibodies and insulitis in the non-obese diabetic mouse.

The predictive value of insulitis, islet cell cytoplasmic antibodies and insulin autoantibodies for insulin-dependent diabetes was studied in young female non-obese diabetic mice. The ontogeny of the three markers was examined cross-sectionally at days 15, 25, 40 and 90 while islet cell antibodies and insulin autoantibodies were studied longitudinally from day 35 or day 144-168 until approximately day 250. Insulitis was first observed at day 40 (50%) and subsequently at day 90 (70%). Islet cell antibodies and insulin autoantibodies were present at day 15 in 46% and 54% of the animals respectively. The rate of islet cell antibodies was slightly higher at day 25 (60%) than at day 40 (40%) and day 90 (54%) whereas antibodies to insulin were present in all samples from day 25-90. At day 40 and day 90 insulitis and insulin autoantibodies were present together in 42% and 70% of the animals, respectively, while insulitis and islet cell antibodies had a lower rate of concordance (17% and 42%, respectively; diabetes rate, 30%). The concordance rates for islet cell antibodies and insulin autoantibodies were 42% at day 40 and 54% at day 90. Concordance for all three markers was first observed at day 40 (17%) which increased to 38% at day 90. In longitudinal studies, islet cell antibodies and insulin autoantibodies were often present together whether or not diabetes supervened. In the islet cell antibody procedure, immunoreactive cells were shown immunohistochemically to correspond with insulin and/or glucagon cells. However, this staining was not suppressible with insulin- or glucagon- absorbed sera, implying the presence of non-hormonal autoantigens. We conclude that the three markers investigated are expressed early after birth and well before clinical symptoms appear in this animal model. Both islet cell antibodies and insulin autoantibodies preceded insulitis but the prevalence rate for each marker or their degree of concordance was different from the anticipated rate of diabetes in our colony. Consequently, the early expression of the three markers alone is not predictive of diabetes although concordance for the two, or all three markers may be of some value. However, no animal developed diabetes without the prior appearance of both islet cell antibodies and insulin autoantibodies.

Animals↗
PubMed1988

Preoperative combined modality therapy for stage III M0 non-small cell lung carcinoma.

More than 1/3 of all non-small cell lung carcinoma (NSCLC) patients present with locally advanced non-metastatic disease. Despite radiation therapy and surgery the survival of these patients remains poor. In an effort to improve upon these results 33 clinical Stage III M0 patients from April 1985 through September 1986 were entered into a Phase II study at Rush-Presbyterian-St. Luke's Medical Center. Treatment included 5-FU by continuous infusion, VP-16, cisplatin and concurrent split course radiation therapy followed by surgical resection when possible. The overall clinical response rate is 74%. Fifty-seven percent of the preoperative group of patients went to surgery with a 100% resectability rate. These patients had a 50% pathologic complete response with no tumor found in the resected specimen. All surgical margins were free of disease and there were no operative deaths. This concurrent combined modality therapy is feasible with the major toxicities being leukopenia, nausea, and vomiting. With an overall median follow-up of 15 months, 36% of the patients remain alive. Overall local control is 71%. Actuarial observed 2 yr. survival is 33% and the median survival is 15 months. Histologic complete response appears to be an early indicator of the efficacy of this treatment regime. With 83% of the resected pathologic complete responders alive without evidence of disease, this preoperative combined modality therapy offers an appealing approach.

Adenocarcinoma↗
PubMed1988

Intra-operative radiation therapy in the treatment of pelvic malignancies: a preliminary report.

Local control of advanced pelvic malignancies, particularly when complete surgical resection is not feasible, is often impeded by dosage limitations in radiation therapy and the intolerance to radiation of normal tissues. This is a preliminary report on the feasibility of improved local control in pelvic malignancies treated by intra-operative radiation therapy, as a radiation boost, in addition to conventional surgical resection and external beam radiation therapy. Fifteen gynaecological malignancies (five cervix, five uterus, four ovary, and one vulva) from Rush Medical College and the University of Navarre, as well as 36 other pelvic malignancies (32 colorectal, 4 genito-urinary) from Rush Medical College were reviewed. All tumours were advanced or recurrent, and all patients were felt to be at high risk of local failure. IORT was administered at a dose range of 10-26 Gy. Our data suggest that the probability of local control improves when IORT is used for primary and for microscopic disease, when the tumour is at least partially resectable, and when the total dose given in IORT and external beam radiation exceeds 70 Gy.

Brachytherapy↗