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Biomedical subjects

K K Tsuboi

Publications and source records attributed to K K Tsuboi.

35 records · Page 2Linked to original sources
PubMed1978

Antiproliferative agents and differential survival between normal and cancer cells.

A basic difference in response between normal cells (primate fibroblasts) and colonic cancer cells (human and rodent) to the antiproliferative action of both N-(phosphonacetyl)-L-aspartate and thymidine is described in this report. Both normal and colonic cancer cells, when cultured in the presence of these agents, cease to increase their cell numbers. Evidence is presented to show that the normal cells respond to deprivation of pyrimidine nucleotide induced by these agents by simple growth arrest, in which a quiescent state may be maintained for prolonged periods without cell death. Cancer cells are shown to respond in a characteristically different manner in which cell division continues accompanied by limited cell survival, with the surviving population representing a balance of these opposing processes. The extent to which these in vitro findings, based on a limited number of comparisons under restrictive artificial conditions, relate to the in vivo state remains to be established.

Adenocarcinoma↗
PubMed1977

Alteration of human placental lactogen by mammary gland.

Human placental lactogen was prepared in high purity and in good yield applying a minimum of purification steps. The isolated hormone was characterized with respect to isoelectric and electrophoretic properties, molecular size (estimated mol. wt. 23 000) and stability to heat, pH and organic solvents. Investigation of in vitro interaction between placental lactogen and mammary gland (mouse, rat) revealed a rapid alteration of hormone with loss of immunoreactivity resulting. The target organ as a selective alteration site of placental lactogen was suggested by a lack of similar action on the hormone by a number of other tissues tested, including liver, kidney and lung. The reaction involving hormone alteration by mammary gland was localized to a particulate-bound enzyme, sedimentable at 10 000 X g and undissociated by sonication in 0.5% Triton X-100. Examination of the reaction products revealed hormone degradation with formation of diffusible components and loss of original electrophoretic identity as well as immunoreactive properties. The reaction characteristics included: pH optimum between 7.5 and 8.0, an absolute salt requirement (NaCl, KCl, at concentration greater than 0.15 M for maximal activation), inhibition by Cleland's reagent and lack of reaction interference by pituitary prolactin.

Animals↗
PubMed1977

Selective inhibition of pyrimidine biosynthesis and effect on proliferative growth of colonic cancer cells.

A highly selective inhibition of de novo pyrimidine synthesis in the intact cell has been demonstrated by the action of N-(phosphonacetyl)-L-aspartate (PALA), a transition-state analog inhibitor of the reaction catalyzed by asparate transcarbamylase. The effect of pyrimidine deprivation induced by this agent on the viability and survival of human normal (WI-38) and colonic cancer cells (HT-29) was examined. The PALA-treated, pyrimidine-deprived cells failed to grow but demonstrated a normal rate of glucose utilization with impaired glycogen synthesis. Pyrimidine deprivation and lack of cell growth were maintained long after PALA removal. Growth inhibition of HT-29 cells by PALA was found to reflect an apparent steady state between newly formed and dying cells induced by limited pyrimidine availability. The highly selective nature of PALA action was confirmed by the ability of an exogenous source of pyrimidine to restore the normal growth pattern of the cell. Significant antitumor activity of PALA was found against a transplantable colonic tumor (line 26) carried in mice.

Animals↗
PubMed1975

Adenylate kinase of human erythrocyte. Isolation and properties of the predominant inherited form.

Adenylate kinase exists in the human erythrocyte in a number of molecular forms with two allels at a single polymorphic locus coding for most of the enzyme forms. The predominant enzyme form, AK a, was purified to constant specific activity in excess of 3000 and appeared homogeneous by chromatography, electrophoresis, and ultracentrifugation. Sedimentation velocity and partial specific volume measurments of AK a yielded values of s20,w = 2.1 S and 0.722 cm-3per g. The molecular weight of the native enzyme was estimated to be 22,500 by sedimentation equilibrium and gel filtration analyses. The molecular weight of the denatured enzyme did not differ, indicating an absence of subunit structure in confirmation of genetic evidence of a single locus coding for the enzyme. The isolated enzyme demonstrated remarkable stability to denaturants (heat, guanidine HCl, urea) in the presence of appropriate stabilizing agents and could not be distinguished from rabbit muscle enzyme on this basis (as well as by a number of other kinetic and physicochemical parameters). The erythrocyte adenylate kinases have a common molecular size but differ in their charge properties. They demonstrate anomalous electrophoretic behavior, migrating anionic to hemoglobin in starch gel, yet exhibit isoelectric points considerably alkaline to hemoglobin (e.g. AK a, pI = 9.0) by isoelectric focusing.

Animals↗
PubMedDate not supplied

Growth and differentiative maturation of the rat enterocyte.

Cells of the intestinal mucosa of the infant and adult rat maintain a pattern of continuous growth, accumulating structural and functional proteins and lipids while migrating the length of the villus column. Cells of jejunal and ileal segments were fractionated sequentially from villus tip to inner crypt and distribution patterns were determined for DNA, total protein, cholesterol, phospholipid, and disaccharidases. Patterns of increasing ratios of protein, lipids, and disaccharidases to DNA were maintained to villus tips, with only slight fall-off of enzymes observed. Distribution profiles of disaccharidases, when computed relative to protein (as seen in previous reports), show distortion of the true cellular distribution pattern of these enzymes as determined by the DNA content of the fractions. Wide variation in cell protein concentrations was evident between jejunal and ileal segments in pre- and postweaned rats. Ileal cells of the suckling rat contained particularly high protein concentrations, which appeared to be largely transitory in nature and related to food intake. Cholesterol and phospholipids were found to be concentrated in the microvillus membrane and account for a significantly large fraction of the cellular content of these lipids.

Animals↗