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Biomedical subjects

S George

Publications and source records attributed to S George.

At least 19 recordsLinked to original sources
PubMed1979

Topography of a flexible ribonucleoprotein helix: protein-protein contacts in Sendai virus nucleocapsids.

Contacts among the three polypeptide species in the flexible helical nucleocapsids of a paramyxovirus were examined with bifunctional protein cross-linking reagents. Polypeptides L and P, minor components of Sendai virus nucleocapsids implicated in viral RNA polymerase activity, were efficiently cross-linked into large complexes, indicating that they enjoy abundant contacts with neighboring protein molecules in the helix. Less reactivity was found in the case of the major structural polypeptide, NP; about half of all molecules of NP formed large cross-linked complexes, most of the rest remaining as monomers along with a small proportion of homodimers and low-order oligomers. Marked heterogeneity in the cross-linking reactivity of NP molecules, which may reflect the conformational quasi-equivalence inherent in a flexible helix, was indicated by the production of several conformers of homodimers and other low-order oligomers of NP, and by failure of the kinetics of NP cross-linking to conform to a simple statistical model of random polmerization. The validity of the statistical model was shown by cross-linking experiments with the rigid helical virus, tobacco mosaic virus.

Capsid↗
PubMed1979

Phase II study demonstrating failure of both a five-drug continuous-therapy regimen and a two-drug pulse-therapy regimen in the treatment of metastatic neuroblastoma: Southwest Oncology Group Study 822.

Twenty-six children greater than 1 year of age with previously untreated stage IV neuroblastoma were randomized to receive either a five-drug regimen (prednisone, cyclophosphamide, actinomycin D, vincristine, and daunorubicin) or a two-drug regimen (cyclophosphamide and vincristine). Complete response rates were 6% and 9% for the five-drug and the two-drug regimens respectively. Partial response rates were 13% and 27% for the five-drug and the two-drug regimens respectively. The mean duration of the seven responses was 9 months, and all 26 patients had died within 2 years. Neither regimen was effective for long-term disease control in these children with neuroblastoma.

Antineoplastic Agents↗
PubMed1978

Metabolic effects of clofibrate in insulin-dependent ketosis-prone diabetic man.

This study examined the effects of clofibrate therapy on basal plasma substrate and hormone concentrations in ketosis-prone insulin-dependent diabetic man. A double-blind crossover design was utilized during a 3-mo period in which clofibrate treatment (1 g b.i.d.) was compared to that of a lactose placebo (1 g b.i.d.). Our results demonstrate that clofibrate treatment resulted in a significant reduction in the concentration of plasma glucose, ketone bodies, free fatty acids, triglyceride, and cholesterol in diabetic man. These beneficial effects were observed without demonstrable changes in circulating concentrations of insulin and glucagon. These observations suggest that in ketosis-prone diabetic man, clofibrate therapy may provide an adjunct to exogenous insulin administration.

Adult↗
PubMed1978

Combination chemotherapy for osteosarcoma.

Because of the great risk for development of pulmonary metastases following amputation for osteosarcoma, 24 consecutive patients with "clinically localized" osteosarcoma of an extremity were given adjuvant combination chemotherapy with adriamycin-cyclophosphamide-high-dose methotrexate-citrovorum factor. Thirteen of these patients remain free of tumor from 11 to 48 months following amputation. The median disease-free survival is estimated to be 18 months and the median survival 27 months. No relapses have been observed in any patients surviving free of disease beyond 23 months. Combination chemotherapy was also given to 16 patients whose disease was not localized; eight with pulmonary metastases at or following diagnosis, one with nodal metastases at diagnosis, two with osteosarcoma following radiation therapy for other malignant tumors, three with osteosarcoma of flat bones, one with parosteal osteosarcoma, and one with multifocal osteosarcoma. Three of this latter group of patients are surviving free of tumor at 8, 17, and 19 months from diagnosis. Two young patients died from complications of methotrexate and adriamycin toxicity.

Adolescent↗
PubMed1977

Pretreatment cytokinetic studies in 94 children with acute leukemia. Relationship to other variables at diagnosis and to outcome of standard treatment.

The relationship of the pretreatment bone marrow mitotic index (MI) and in vitro 3H-thymidine labeling index (LI) to other variables present at diagnosis and to the outcome of standard therapy was examined in a series of 94 children with acute leukemia (71 ALL, 23 AML). The range of observed values at diagnosis was extremely broad, from less than 1% labeled cells to more than 25%. The median LI% for all patients studied was 5.2%; the median MI% was 0.3%. The values for AML and ALL did not differ significantly despite older age, higher initial white blood cell (WBC) counts, and poorer response to therapy of AML patients. The initial MI and LI were positively correlated with each other, but unrelated to age or initial WBC count in either ALL or AML. However, the LI and MI were significantly higher (p less than 0.01) in the group of 10 children of 54 studied with ALL whose blasts formed spontaneous rosettes with sheep red blood cells at 37 degrees C. The initial LI and MI were not shown to be related to the likelihood of attaining a complete response or to the length of remission in either ALL or AML. There was thus no evidence that either the initial MI or LI% of marrow blasts was of any prognostic significance in children with acute leukemia.

Age Factors↗
PubMed1976

Evaluation of dose and schedule of L-asparaginase in multidrug therapy of childhood leukemia.

Six regimens utilizing L-asparaginase in doses of 6,000 IU/M2, 2,000 IU/M2, and 500 IU/M2 in two separate schedules (consecutive and intermittent) along with vincristine and prednisone yielded remarkably similar response rates, approximating 70%, in 306 previously treated children with acute leukemia in relapse. The addition of daunorubicin to one regimen did not alter the response rate. Hypersensitivity reactions occurred in 5% and hyperglycemia in 7%. Lower doses of L-asparaginase significantly reduced the hypersensitivity rate but no such pattern was noted for hyperglycemia. A history of prior resistance to prednisone and vincristine significantly reduced the response rate.

Acute Disease↗
PubMed1976

Metabolism of 3-(hydroxymethyl)-8-methoxychromone in the rat. II. Classification and identification of urinary drug metabolites.

1. Five metabolites were isolated from the urine of dogs dosed with 3-(hydroxymethyl)-8-methoxy[4-14C]chromone. These were identified as 8-methoxychromone, 2-hydroxy-3-methoxyacetophenone, 3-(hydroxymethyl)-8-hydroxychromone, 8-hydroxychromone and 2,3-dihydroxyacetophenone. 2. These compounds were also present in the urine of rats treated with labelled drug, together with unchanged drug and two intermediate metabolites, 3-carboxy-8-methoxychromone and 3-(carboxymethyl)-8-hydroxychromone. 3. In addition to the unconjugated labelled compounds, glucuronides and sulphates were identified. 4. Quantitative data were obtained for all of the 20 labelled compounds in rat urine. 5. A scheme is presented for the biotransformation of 3-(hydroxymethyl)-8-methoxychromone in rats and dogs, and a mechanism for scission of the gamma-pyrone ring is suggested.

Animals↗
PubMed1975

Comparison of prednisolone, vincristine, methotrexate, and 6-mercaptopurine vs. vincristine and prednisone induction therapy in childhood acute leukemia.

This was designed to compare vincristine-prednisone (VP) vs. prednisolone, vincristine, methotrexate, and 6-mercaptopurine (POMP) with respect to response rates and toxicity for induction therapy in acute leukemia. Children with acute lymphoblastic, acute undifferentiated, or acute stem cell leukemia were stratified on the basis of initial leukocyte count and age, then randomly assigned to POMP or VP induction therapy. On the POMP regime, 19/34 (56%) achieved complete remission (CR), 7 achieved partial remission (PR), and 5 did not respond (NR). Three died prior to day 25 of the study. On the VP regime, 37/39 (95%) had CR, and 2 NR. On the VP regime neither sepsis nor toxicity were significant problems. The POMP regime had a higher incidence of sepsis and other toxicities frequently causing therapy interruption, but not enequivocally causing the poor response rate. Several other factors were evaluated as possible causes for the lack of response to POMP therapy.

Acute Disease↗
PubMed1975

Adriamycin in the treatment of childhood acute leukemia. A Southwest Oncology Group study.

Sixty-six children with acute leukemia, in advanced stages of their disease and resistant to conventional chemotherapy, received adriamycin for remssion induction. Seventeen of 46 (37%) evaluable children with acute lymphocytic leukemia achieved a complete remission, and 5 (11%) achieved a partial remission. Two of 12 evaluable children with acute myelogenous leukemia achieved a complete remission, while an additional 3 achieved a partial remission. Two children with erythroleukemia also achieved a complete remission. Previous therapy with daunorubicin did not affect the response rate. The main toxicities observed with adriamycin were myelosuppression, fever, nausea and vomiting, stomatitis, alopecia, and cardiac toxicity (ST segment changes and arrhythmias).

Adolescent↗
PubMed1975

Adriamycin in the treatment of childhood solid tumors. A Southwest Oncology Group study.

Ninety-eight children with solid tumors resistant to conventional chemotherapy received adriamycin 90 mg/m2, either as a single intravenous injection or in 6 divided doses administered every 6 hours. Of the 88 evaluable children, 6 (7%) achieved a complete response and 26 (29%) achieved a partial response. Tumors which demonstrated significant response rates were: neuroblastoma (9/18), Wilms' tumor (7/13), rhabdomyosarcoma (4/11), and lymphoma (4/8). The toxicities observed with this regimen included: alopecia, leukopenia, thrombocytopenia, nausea, vomiting, stomatitis, febrile episodes, and ST-segment changes.

Adolescent↗
PubMed1975

Unfavorable prognosis of acute leukemia in infancy.

Pretreatment characteristics of 48 infants (under 2 years of age) with leukemia treated over a period of 18 years at a single institution were studied in relation to response to therapy, extramedullary involvement, and survival. In order to provide a basis of comparison, 45 of the infants were each paired with an older (2-9 years of age) leukemic child, who had the same race, and disease type, who was treated within the same period of time and received similar suportive care and chemotherapy, and when possible, was of the same sex. The overall median survival times of infants and their pairmates were 211 days and 445 days, respectively. Initial status of the spleen was the single significant factor in relation to the length of survival. Median survival time for infants with splenomegaly was 186 days compared to a median survival time of 414 days for infants without splenomegaly. The complete response rate was 75% for infants and 80% for the pairmates. Median duration of remission was 84 days for infants and 280 days for their pairmates. Initial peripheral leucocyte count was significantly related to the duration of remission; patients with very high leucocyte counts had the shortest remissions. The duration of remission increased throughout the period covered by this study, however, prognosis relative to pairmates remained poor. Central nervous system leukemia occurred in 44% of infants and 40% of the pairmates; incidence of CNS leukemia was much higher (70%) in infants under one year of age than in infants one year old (37%). Extramedullary leukemia occurred at other sites in 46% of the infants and 31% of the pairmates. The only pretreatment characteristic of prognostic importance for predicting extramedullary involvement was the patient's age at diagnosis.

Acute Disease↗
PubMed1975

Analysis of traditional strategies to combat world hunger and their results.

The traditional strategies proposed for development of the agricultural production of the underdeveloped countries are examined in this article. It is shown that the application of these strategies in the past has proven insufficient to eliminate world hunger. The limitations of these strategies are discussed and proposals are made for achieving the agricultural development in the underdeveloped world that will be necessary to eliminate hunger in the near future.

Agriculture↗
PubMed1975

Assessment of the world food situation-present and future.

The widespread bad harvests of 1972 in various regions of the world, the consequent reduction in grain reserves, the rapid rise in food prices almost everywhere and its impact on inflation, all have served to draw renewed attention to the problem of hunger which affects millions of human beings in the world today. During the 1974 United Nations World Food Conference many important matters relating to this problem were debated: the creation of international grain reserves; problems concerning world trade of foodstuffs; the current difficulties with certain key agricultural production factors, such as fertilizers; the necessity for organizing a worldwide information system on the situation; and prospects of various harvests and threats of famine in underdeveloped countries. It is often the case that discussion of the hunger problem does not correspond to the gravity of the crisis; true causes of the present situation are not examined, and measures are not adopted that will once and for all--for the first time--abolish hunger. In view of the prospect that the real issues are often ignored, the Transnational Institute provides this analysis in an attempt to clarify what must be done to abolish hunger in the belief that this is within the reach of humanity when and if we are determined to end the irrationalities of the present economic system and the relations of domination which some individuals and countries seek to continue.

Agriculture↗