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Biomedical subjects

S Reddy

Publications and source records attributed to S Reddy.

At least 253 records · Page 14Linked to original sources

Electrical impedance in assessing human body composition: the BIA method.

Fundamental aspects of the body impedance analysis (BIA) method were investigated to determine limitations. This method measures body impedance with a low-level (800 microA) 50-KHz current conducted through the tissues. A linear regression equation was proposed to relate impedance measurements to total body fat. The hydrostatic densitometric method (underwater weighing) was used to validate the proposed mathematical expression. A correlation coefficient of 0.98 between these two methods was obtained. The overall results from this study indicate the usefulness of the BIA method in determining percent body fat in humans provided body fluids are not perturbed several hours before the measurements.

Adipose Tissue↗

An immunofluorescent study of insulin-, glucagon-, pancreatic polypeptide- and somatostatin-containing cells in the early ovine fetal pancreas.

Using antisera to insulin, glucagon, pancreatic polypeptide (PP) and somatostatin, the localization and cellular distribution of the four hormones were investigated in the sheep fetal pancreas of day 40-45 gestation by immunofluorescence. All four hormones were immunolocalized at this early gestational period. The endocrine cell types had a characteristic distribution and were present in different numbers. Insulin and glucagon immunoreactive cells were seen in larger numbers compared to fetal PP and somatostatin cells and were located either in the developing islets or as single scattered cells in the epithelium of the embryonic ductules. These cells became more confined to the developing islets at later stages of gestation. In the pancreas of day 40-45 fetuses PP cells were less numerous than glucagon and insulin cells while somatostatin cells were seen rarely. However, PP and somatostatin cells became more numerous at later stages of gestation. Our studies demonstrate the presence of insulin, glucagon, PP and somatostatin within distinct cell types in the early sheep fetal pancreas.

Animals↗

v-src mutations outside the carboxyl-coding region are not sufficient to fully activate transformation by pp60c-src in NIH 3T3 cells.

Previous studies have shown that carboxyl-terminal mutation of pp60c-src can activate its transforming ability. Conflicting results have been reported for the transforming ability of pp60c-src mutants having only mutations outside its carboxyl-terminal region. To clarify the effects of such mutations, we tested the activities of chimeric v(amino)- and c(carboxyl)-src (v/c-src) proteins at different dosages in NIH 3T3 cells. The focus-forming activity of Rous sarcoma virus long terminal repeat (LTR)-src expression plasmids was significantly reduced when the v-src 3' coding region was replaced with the corresponding c-src region. This difference was masked when the Rous sarcoma virus LTR was replaced with the Moloney murine leukemia virus LTR, which induced approximately 20-fold more protein expression, but even focus-selected lines expressing v/c-src proteins were unable to form large colonies in soft agarose or tumors in NFS mice. This suggests that pp60c-src is not equally sensitive to mutations in its different domains and that there are at least two distinguishable levels of regulation, the dominant one being associated with its carboxyl terminus. v/c-src chimeric proteins expressed with either LTR had high in vitro specific kinase activity equal to that of pp60v-src but, in contrast, were phosphorylated at both Tyr-527 and Tyr-416. Total cell protein phosphotyrosine was enhanced in cells incompletely transformed by v/c-src proteins to the same extent as in v-src-transformed cells, suggesting that the carboxyl-terminal region may affect substrate specificity in a manner that is important for transformation.

Animals↗

Additive and synergistic interaction of atrial natriuretic peptide and volume expansion.

To investigate whether atrial natriuretic peptides (ANP) are entirely responsible for the natriuresis of volume expansion (VE), we studied the natriuresis from acutely snared and nonsnared kidneys of rats undergoing sustained saline VE and subsequent infusion of maximal doses of ANP (atriopeptin II), or vice versa. Fractional excretion of Na (FENa) was increased from control (0.15 +/- 0.03%) to 4.6 +/- 0.6% by VE and to 10.9 +/- 1.5% by subsequent ANP infusion. With ANP alone FENa increased from control (0.24 +/- 0.04%) to 2.6 +/- 0.3%, and to 10.8 +/- 0.9% with VE, showing additive effects by both. Natriuresis with VE was significantly greater than with ANP alone (P less than 0.01) and both exhibited synergism, producing significantly greater natriuresis in the presence of the other than alone (P less than 0.05 for both). A reduction in perfusion pressure inhibited the effects of ANP and reduced that of VE. Natriuresis was produced by ANP independently of changes in glomerular filtration rate. It is concluded that 1) VE and ANP produce natriuresis by different renal mechanisms and that therefore, ANP can only account for part of the natriuresis of sustained VE; 2) the two have a synergistic interaction on natriuresis, probably through an intrarenal mechanism.

Animals↗

Continuous infusion of etoposide, bolus administration of cisplatin, and simultaneous radiation therapy in previously treated patients with small cell bronchogenic carcinoma.

Thirty-one patients with previously treated small cell bronchogenic carcinoma were treated with split-course radiation therapy and concurrent cisplatin and etoposide. Twenty-four patients (78%) had clinical partial or complete responses. Median survival from the time of salvage was 6.3 months. Fifty-eight percent of the patients failed on therapy initially in sites outside the radiation port. Hematologic toxicity was moderate. Concurrent cisplatin, etoposide, and split-course radiation therapy is feasible and active in the treatment of small cell bronchogenic carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Concomitant therapy with infusion of cisplatin and 5-fluorouracil plus radiation in stage III non-small cell lung cancer.

Based on our experience with head and neck cancer, we have developed an every-other-week, split-course schedule for giving combined cisplatin and 5-fluorouracil infusion and radiation to patients with regionally advanced non-small cell lung cancer for a limited number of cycles prior to planned resection. Sixty-four patients having stage III disease without distant metastases were treated with 4 cycles of combined chemotherapy and radiation to 40 Gy and were offered surgical resection. Thirty-nine patients (61%) underwent surgery. Nine had no residual cancer. No correlation was noted between clinical and histologic responses in the surgery group, but histologic response correlated with subsequent outcome. Survival was 58% at 1 year, 33% at 2 years, and 22% at 3 years. Although encouraging, the overall dismal prognosis of this disease has led us to pursue further improvements in protocol design prior to phase III testing of this concept. To this end, etoposide has been added to the above regimen, extending the cycles from every other week to every third week.

Antineoplastic Combined Chemotherapy Protocols↗

Phase II trial of therapy with etoposide, 5-fluorouracil by continuous infusion, cisplatin, and simultaneous split-course radiation in stage III non-small cell bronchogenic carcinoma.

Survival of patients who have clinical stage IIIM0 non-small cell bronchogenic carcinoma remains relatively short despite treatment with either surgery or radiation. Results from a phase II study of simultaneous continuous infusion of 5-fluorouracil, cisplatin, and split-course radiation with or without surgery indicate that median survival duration in patients treated with this combined modality approach may be better than the median survival for patients treated with radiation alone. Etoposide has been added to this regimen, and 32 stage IIIM0 non-small cell lung cancer patients have been treated with the 3-drug regimen resulting in a 73% clinical partial remission rate. No residual tumor was found in 6 of 12 patients who had pulmonary resection after 4 courses of chemotherapy and radiation. The sites of failure in 8 patients with recurrent disease are as follows: local only, 3; distant only, 4; and local and distant, 1. The major toxicities have been leukopenia, nausea, and vomiting. The median leukocyte nadir was 2,400/mm3. A leukocyte count less than 1,000/mm3 was observed in 2 patients (7%), 1 of whom died of progressive pneumonia. All patients experienced nausea, vomiting, and anorexia. Severe esophagitis, dermatitis, and pneumonitis were not observed. Survival analysis has not been done because median follow-up time (326 days) is relatively short.

Antineoplastic Combined Chemotherapy Protocols↗

Human lung tumor growth established in the lung and subcutaneous tissue of mice with severe combined immunodeficiency.

We report here that a mouse mutant (C.B-17 scid) which lacks functional B- and T-lymphocytes can be used to propagate a human lung tumor. The heterotransplanted tumor cells generated palpable s.c. tumors by 18 days in 100% of the mice inoculated s.c. with greater than 4 X 10(6) cells. All tumors grew progressively with no sign of regression. A portion of the scid mice given injections i.v. of the human lung tumor cells developed multiple tumor nodules in the lung by 15 weeks after the inoculation of tumor cells. The tumor nodules were shown by karyotype analysis to be human cells, and the histopathology of the tumor nodules revealed a pattern of growth that was consistent with that of the original tumor. The human lung tumor used in the study expresses an Mr 160,000 cell surface glycoprotein that has been shown to occur on a large proportion of human lung tumors and tumor cell lines. A monoclonal antibody specific for Mr 160,000 glycoprotein was used to demonstrate that this tumor-associated antigen is stably expressed by the s.c. tumors and the lung tumor nodules in the scid mice. The mutant mice with this severe combined immunodeficiency represent a new and viable model for propagating human tumors and for evaluating the efficacy of novel drug delivery protocols in the treatment of human cancer.

Animals↗

Radiation therapy in primary carcinoma of the vagina.

A retrospective analysis of 32 patients with carcinoma of the vagina treated with curative radiotherapy between 1965 and 1981 is presented. Squamous cell carcinoma was the most common histologic type, found in 78% of the patients. Patients were staged according to the FIGO system. Stage I and II disease was found in 8 and 18 patients, respectively. Six patients had either Stage III or IV disease. The absolute survival rate was 100% for Stage I and 72% for Stage II patients. The pattern of failure was analyzed. All patients who failed had done so within 14 months of completion of treatment. Treatment failure in the pelvis occurred only in 16% of the patients with early disease (Stages I and II) while 81% of the patients with late stage had failed in the pelvis.

Adult↗

Simultaneous cisplatin fluorouracil infusion and radiation followed by surgical resection in regionally localized stage III, non-small cell lung cancer.

Sixty-four patients with stage III (M omicron) non-small cell lung cancer were treated with cisplatin fluorouracil infusion chemotherapy and simultaneous radiation therapy for 5 days every other week. A total of 4 cycles (40 Gy) was followed by attempted surgical resection. Clinical response to the preoperative treatment included 5 (8%) complete and 32 (48%) partial responses. Thirty-nine (61%) underwent the planned operation, and in 9 (23%) of these patients the resected specimens were histologically negative. Clinical assessment failed to predict histological response. With 17 months median follow-up (range, 2.4-29 months), estimated 1-year survival was 61% and median survival was 16 months for all patients.

Adult↗

Analysis of polyomavirus middle-T-antigen-transformed rat cell variants expressing different levels of pp60c-src.

We characterize two independent variant cellular clones which arose following in vitro passage of polyomavirus middle-T-antigen (MTAg)-transformed FR3T3 cells expressing RNA complementary to c-src mRNA. These clones were initially flat and underwent morphologic transformation at a high frequency to a phenotype indistinguishable from that of parental MTAg-transformed FR3T3 cells. Biochemical analysis of the flat clones prior to phenotypic conversion revealed that these cells synthesized little detectable pp60c-src and had correspondingly low levels of pp60c-src protein kinase activity and MTAg-associated protein kinase activity. The flat cell clones did not possess detectable focus-forming activity, were not capable of detectable anchorage-independent growth, and had saturation densities and doubling times below those normally observed for FR3T3 cells. Following conversion of the flat clones to a shape resembling that of typical MTAg-transformed cells, the abundance of pp60c-src, pp60c-src kinase activity, and MTAg-associated in vitro protein kinase activity were all restored to the levels found in the parental MTAg transformants. These cells had growth rates, focus-forming activities, anchorage-independent growth rates, and saturation densities similar to those of the parental MTAg-transformed rat cells. These data provide additional evidence that maintenance of a transformed phenotype by polyomavirus MTAg in established rat cell lines depends, at least in part, on a minimal threshold level of pp60c-src.

Animals↗

Ovarian carcinoma: adjuvant treatment with P-32.

Twenty-eight patients with ovarian carcinoma received 555 MBq of labeled chromic phosphate (P-32) intraperitoneally. Indications for treatment included a high-grade tumor, extracapsular involvement, positive cytologic findings, or residual tumor. Fifteen patients (group 1) had stage I, II, or III completely resected tumor; 13 patients (group 2) had microscopic or less than 3-mm lesions at second-look laparotomy following combination chemotherapy. A major complication occurred in one patient; two patients had minor complications. Overall, 24 of 28 patients (85.7%) were alive at 11-77 months; 23 (82.1%) had no evidence of tumor. Fifteen of 15 (100%) group 1 patients and eight of 13 (61.5%) group 2 patients did not have tumor relapse after 30 months and 28 1/2 months, respectively. P-32 was found to be an effective adjuvant treatment in a select group of patients with ovarian carcinoma who were at high risk for intraabdominal recurrence.

Brachytherapy↗

Longitudinal study of first phase insulin release in the BB rat.

First phase insulin release was measured in response to intravenous glucose given weekly from approximately day 40 in 6 BB rats which subsequently developed diabetes and in age-matched non-diabetic (n = 15) and normal Wistar rats (n = 8) until day 180. The mean sequential insulin responses in BB rats with and without diabetes were significantly lower (p = 0.008 and less than 0.0001, respectively) than in normal rats from an early age. Five diabetic BB rats showed a progressive decline in first phase insulin release immediately prior to glycosuria, with the impaired phases ranging from 25-50 days. However, protracted periods of low first phase responses were also seen in several aglycosuric BB rats, which showed histological evidence of insulitis and B-cell loss. Our findings demonstrate that, although most BB rats with diabetes show a progressive impairment of B-cell function preceding the disease, this aberrant phase can also be present in BB rats which remain aglycosuric. Impaired first phase insulin release in response to serial intravenous glucose tolerance tests may not be a reliable predictor of Type 1 (insulin-dependent) diabetes in this animal model.

Animals↗

Immunolocalization of insulin, glucagon, pancreatic polypeptide, and somatostatin in the pancreatic islets of the possum, Trichosurus vulpecula.

Antibodies to insulin, glucagon, pancreatic polypeptide (PP), and somatostatin were used in the immunofluorescence procedure to demonstrate localization of the four hormones in cells of the pancreatic islets of the brushtailed possum, Trichosurus vulpecula. Most pancreatic islets revealed some differences in the topographical distribution and cell number of each endocrine cell type. Insulin immunoreactive cells were observed in most islets where they occurred as groups of cells peripherally and within the islet. In several islets glucagon cells were the predominant cell population and were distributed peripherally as well as centrally. Pancreatic polypeptide cells were fewer in number and usually occurred as single cells within the islet. Cells immunoreactive to antisomatostatin serum were observed in varying numbers in the peripheral and central regions of the islet. The present immunofluorescence study demonstrates differences in the topographical distribution of the four major pancreatic hormones between a marsupial species and several of the eutherian mammals.

Animals↗