Potentiation of Rho-A-mediated lysophosphatidic acid activity by hyperinsulinemia.

We have shown previously that insulin promotes phosphorylation and activation of farnesyltransferase and geranylgeranyltransferase (GGTase) II. We have now examined the effect of insulin on geranylgeranyltransferase I in MCF-7 breast cancer cells. Insulin increased GGTase I activity 3-fold and augmented the amounts of geranylgeranylated Rho-A by 18%.

Effects of insulin on prenylation as a mechanism of potentially detrimental influence of hyperinsulinemia.

To investigate the cause and effect relationship between hyperinsulinemia and the increased amounts of farnesylated p21Ras, we performed hyperinsulinemic euglycemic clamps in normal weight volunteers as well as in normal mice and dogs. Insulin infusions significantly raised the amounts of farnesylated p21Ras in the white blood cells of humans, in liver samples of mice and dogs, and in aorta samples of mice. Obese hyperinsulinemic individuals and dogs (made hyperinsulinemic by surgical diversion of the pancreatic outflow from the portal vein into the vena cava) displayed increased amounts of farnesylated p21Ras before the hyperinsulinemic clamps.

Preliminary evaluation of platinum transferrin (MPTC-63) as a potential nontoxic treatment for breast cancer.

Transferrin receptors on proliferating and malignant cells are well documented. Faulk et al. demonstrated transferrin receptors in breast carcinoma by immunofluorescence.

Analysis of plume emissions after papovavirus irradiation with the carbon dioxide laser.

This study was undertaken to evaluate potential inhalation hazards to operating room personnel after irradiation of tumors with the carbon dioxide laser. Cellular debris was analyzed for viability using labeled nucleotides and labeled glucose. In this way the plume was investigated for the presence of material with oncogenic potential.

Binding of platinum to human transferrin.

A complex of platinum and human transferrin has been formed by appropriately combining apotransferrin (metal free protein) and potassiumchloroplatinate (K2PtCl4). Atomic absorption spectroscopy indicated that both primary bind sites on the protein participated in the complex. Electron paramagnetic resonance (EPR) examination showed that the bound platinum was not paramagnetic, and thus it is highly probable that the Pt ion is in the +2 oxidation state.

Electron paramagnetic resonance investigation of high-spin iron (III) in cancer.

The concentration of iron (III)-transferrin (IT) in whole blood and serum, along with another high-spin (five unpaired electrons) iron complex (probably IT) accumulated by tumor tissue, was investigated by electron paramagnetic resonance (EPR) spectroscopy during the development of Murphy-Sturm rat lymphosarcoma. The observed changes in concentration (microgram/ml) of IT in sera/blood were generally complementary to those from tissue and the character of the modifications suggested the existence of three distinct phases of systemic response to the implantation: (1) an initial response, evidenced by a sharp reduction in serum IT and somewhat high tissue-IT concentration (microgram/g); (2) a period in which the tumor is (2) a period in which the tumor is becoming established, indicated by relatively constant tissue IT levels and near normal serum IT; and (3) the onset of rapid cell multiplication, characterized by increased total tissue-IT accumulation that rises to above 200% of normal available serum iron, increasing tissue-IT concentration, and rapidly declining serum-IT concentration. The results suggest that, in the face of an implanted tumor there are two detectable abnormal serum-IT responses: (1) an initial change, probably due to systemic blockage of iron reutilization; and (2) extraction of IT from serum by multiplying tumor cells, which is probably a major contributor to reduced serum-IT levels and ultimately anemia.

Correlation of metabolic and chemiluminescent responses of granulocytes from three female siblings with chronic granulomatous disease.

Polymorphonuclear leukocytes (PMNL) from children with atypical chronic granulomatous disease (CGD), their mother and siblings, and normal controls were studied in regard to glycolytic and hexose monophosphate shunt activities in the resting, methylene blue-stimulated, and phagocytizing states. PMNL from the patients with CGD had normal glycolytic and hexose monophophate shunt activities in the resting state and after stimulation with methylene blue. However, stimulation of the hexose monophosphate shunt after phagocytosis was greatly decreased.

Factors affecting filamentation in Candida albicans: changes in respiratory activity of Candida albicans during filamentation.

Glucose metabolism and respiration of Candida albicans were compared under conditions which permitted either maximal filamentous or maximal yeast growth. Changes in metabolism were monitored by comparing the quantities of ethanol produced, CO2 evolved, and oxygen consumed. Filamenting cultures produced more ethanol and less CO2 than yeasts, with oxygen consumption in the former concomitantly slower than that of the latter.

Cytochalasin B: effect on phospholipid metabolism and lysosomal enzyme release by leukocytes;

The effect of cytochalasin B on phospholipid metabolism and beta-glucuronidase extrusion by polymorphonuclear leukocytes from guinea pid peritoneal exudates has been studied. Cytochalasin B inhibited the engulfing of starch granules by leukocytes, but it enhanced the incorporation of 32-Pi into phosphatidic acid and the phosphoinositidesmit also stimulated the release of beta-glucuronidase into the incubation medium in the presence or absence of starch granulesmkinetic studies showed that the effects of cytochalasin B on 32-Pi incorporation into phosphatidic acid and the phosphoinositides, and the release of beta-glucuronidase into the extracellular medium were comparablempulse-chase experiment revealed that cytochalasin B did not stimulate the isotopic decay of prelabeled lipids, indicating that cytochalasin B increased the radiophosphorus activity of phosphatidic acid and the phosphoinositides by increasing the synthesis of these lipidsmthe incorporation of myo-[2-3H]inositol into the phosphoinositides was also enhanced in the presence of cytochalasin B, but the incorporation of [methyl-14-C] choline into phosphatidylcholine and sphingogonyelin was unchanged;

Factors affecting filamentation in Candida albicans: relationship of the uptake and distribution of proline to morphogenesis.

When glucose was present in high concentration, Candida albicans formed filaments in a phosphate-buffered medium, regardless of the nitrogen source. In lower concentrations of glucose, filamentation occurred only when various members of the glutamate, succinyl, or acetoacetyl-coenzyme A families of amino acids were used as sole nitrogen sources. Yeast morphology could be maintained either by replacing the amino acids in the medium with ammonium chloride or by making the medium high in phosphate or biotin.

Impaired chemiluminescence during phagocytosis of opsonized bacteria.

A simple technique is presented for rapid screening of leukocytes of patients suspected of having a defective intracellular mechanism for the bactericidal and digestive disposal of bacteria.