Insulin and insulin-like growth factor I binding to cultured rat glomerular mesangial cells.

The potential effects of insulin and insulin-like growth factor I (IGF-I) on mesangial cell (MC) metabolism and growth were examined. Radiolabeled insulin or IGF-I were incubated with cell membranes from rapidly proliferating (subconfluent) or nonproliferating (confluent) MC in the presence of increasing concentrations of unlabeled heterologous and homologous ligands (0-10(-6) M). Insulin binding to MC was specific and saturable, with Scatchard analysis of binding data showing the characteristic curvilinear plot. The predicted insulin binding maximum of 4.2 X 10(-12) M/100 micrograms protein for a theoretical high affinity site was consistent with a relatively low density of receptors, which were the same in proliferating and nonproliferating cell preparations. Specific binding of IGF-I to MC was also demonstrated. Binding data for membranes from proliferating cultures generated a linear Scatchard plot, which predicted a binding maximum of 3.5-9.7 X 10(-11) M/100 micrograms protein and a Kd of 2.0-3.2 X 10(-9) M. In contrast, membranes from nonproliferating cultures had no demonstrable specific binding of IGF-I. Covalent cross-linking of radiolabeled IGF-I to membranes from subconfluent cells demonstrated specific binding to a 145K membrane protein. A 95K membrane protein from a partially purified receptor preparation demonstrated autophosphorylation when incubated with 5 X 10(-9) M IGF-I. Incubation of MC with 10(-9) M IGF-I doubled cellular growth rates, an effect that could be duplicated only with high concentrations (10(-6) M) of insulin. These observations indicate that MC express predominantly receptors for IGF-I, and that growth stimulatory effects of physiological concentrations of IGF-I and pharmacological concentrations of insulin are probably mediated through the IGF-I receptor.

External irradiation in the management of stage II endometrial carcinoma.

Twenty-nine patients with stage II endometrial carcinoma were reviewed and the possible risk factors involved in state II disease are presented. Twenty-four patients received external irradiation as part of their treatment with or without intracavitary or intravaginal radium and/or TAH BSO. The 5-year actuarial survival in our series was 81.4%. The data showed that preoperative external irradiation can be effectively administered without undue complication. A strong argument against the traditional use of preoperative intracavitary radium is presented. Preoperative external irradiation administered with a 4-field box technique to deliver a minimum dose of 5000 rad in 5--6 weeks to all the structures at risk is the recommended treatment for stage II endometrial carcinoma.

Localization of pyruvate kinase isozymes in bovine kidney and comparison of these patterns with those of lactate dehydrogenases and aldolases.

Electrophoretic and immunofluorescence analysis were used to study the distribution of pyruvate kinase isozymes in the bovine kidney. Electrophoretic analysis demonstrated the presence of large amounts of K4 plus small amounts of K-M hybrids in cortical, medullary, and papillary sections cut from the kidney. Nearly all of the K-L hybrids seen in whole kidney extracts were found in cortical sections. Immunofluorescence of frozen sections revealed the presence of type L subunits in the tubules but the complete absence of this subunit type in flomeruli. Glomeruli do contain large quantities of pyruvate kinase isozymes, probably K4 and K-M hybrids, that cross-react with antibodies produced against type M pyruvate kinase. Type L-containing forms of pyruvate kinase and aldolase type B both appear to be found in cell types thought to be capable of catalyzing of gluconeogenesis, while type K pyruvate kinase and type A aldolase are found in predominantly glycolytic cell types of the kidney. Lactate dehydrogenase isozymic patterns appear to be less closely correlated with glycolytic versus gluconeogenic functions of the kidney but may be determined more directly by other metabolic functions.