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Biomedical subjects

K Muta

Publications and source records attributed to K Muta.

At least 91 records · Page 5Linked to original sources
PubMed1990

Mechanisms involved in the development of adriamycin resistance in human leukemic cells.

We have developed three adriamycin (ADR)-resistant K562 sublines with different degrees of resistance. These sublines show a decreased accumulation and an increased efflux of ADR in proportion to the degree of resistance. Two membrane proteins (mol. wt 170,000 and 230,000) reactive with monoclonal antibody against P-glycoprotein were highly expressed in both the K562/ADR200 and the K562/ADR500 subline. Less resistant K562/ADR80 cells contained only small amounts of mol. wt 230,000 protein. Thus, the level of P-glycoprotein expression was not proportionate to the degree of ADR efflux. Verapamil treatment could not completely reverse ADR resistance. No significant change of glutathione-s-transferase activity nor in the level of DNA topoisomerase II was detected in resistant sublines. In our sublines it seems that P-glycoprotein is one of the mechanisms for resistance, but additional mechanisms may be involved.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Percutaneous penetration of acyclovir through excised hairless mouse and rat skin: effect of vehicle and percutaneous penetration enhancer.

The effects of vehicle and percutaneous penetration enhancer on the penetration of acyclovir through excised hairless mouse and rat skin were investigated. Four solvents, propylene glycol (PG), ethanol (ET), isopropanol (IPA), and isopropyl myristate (IPM), were employed as vehicles, in combination with four enhancers, 1-farnesylazacycloheptan-2-one (7FU), 1-geranylazacycloheptan-2-one (7GU), 1-geranylazacyclopentan-2-one (5GU), and 1-dodecylazacycloheptan-2-one (Azone). Acyclovir was suspended in vehicles to avoid the effect of the thermodynamic activity of acyclovir in the vehicle. The penetration of acyclovir through hairless mouse skin from IPA was enhanced by 7GU, whereas that from IPM was not affected. All combinations of vehicle and penetration enhancer were examined using rat skin. No effect of the enhancers was observed in the IPM vehicle. The estimated solubility parameters of vehicles and enhancers indicated that the polarities of IPM and the enhancers are similar, which prevents effective penetration of the enhancers from IPM. However, the penetration of acyclovir from the other vehicles was increased by the enhancers. The combination of hydrophilic vehicle and hydrophobic enhancer resulted in a large enhancing effect. The disappearance of the enhancers from the vehicle correlated with their enhancing activity, but other factors also seemed to affect the penetration enhancement of acyclovir.

Acyclovir↗
PubMed1990

Abnormality of platelet membrane glycoprotein GPIIb in a myelodysplastic syndrome with 3q inversion presenting with marked dysmegakaryopoiesis.

Platelet membrane glycoproteins were analyzed in a case of myelodysplastic syndrome with inv(3) (q21q26) presenting with prominent dysmegakaryopoiesis by three different labelling techniques for surface proteins. Markedly decreased level of platelet membrane glycoprotein GPIIb was observed in the patient's platelets by terminal sialic acid labelling method, whereas no significant changes in the levels of glycoproteins including GPIIb could be detected either by penultimate galactose labelling or by tyrosine/histidine labelling. These results indicate a decreased sialylation of GPIIb in the patient's platelets, implying aberrant process in thrombopoiesis in the disease.

Bone Marrow Examination↗
PubMed1988

Regulation of biosynthesis and phosphorylation of P210bcr/abl protein during differentiation induction of K 562 cells.

The changes of P210bcr/abl and other tyrosine phosphorylated proteins in K562 cells during growth and differentiation were studied by metabolic labeling with 32PO4 and immunoprecipitation with anti-phosphotyrosine sera. The anti-phosphotyrosine sera recognized P210bcr/abl and other phosphoproteins with mol wt of 150, 115, 100, 70 and 64 kD. The 2-day incubation of K562 cells with inducers for differentiation, hemin, sodium butyrate and TPA, decreased the level of P210bcr/abl protein and other phosphoproteins. Inhibitors of tyrosine protein kinase, amiloride and genistein, also reduced the phosphorylation of P210bcr/abl protein and other substrates, but did not induce differentiation of the cells. Although most of these additives inhibited the cell growth, cytotoxic agents such as adriamycin, vincristine and Ara-C did not affect the level of P210bcr/abl protein. The experiments using 35S-methionine labeled cells and the immunoprecipitation with anti-abl sera suggested that reduced biosynthesis but not dephosphorylation of P210bcr/abl protein mainly accounted for the reduction of P210bcr/abl protein reacting to anti-phosphotyrosine sera in differentiation-induced cells. These results indicate that the reduction of P210bcr/abl protein synthesis plays some roles in cellular differentiation of K562 cells.

Cell Differentiation↗
PubMed1988

Possible mechanism of ineffective erythropoiesis by an altered transferrin receptor cycle in erythroleukemia.

Involvement of the transferrin receptor cycle was noted in erythroblasts from a patient with erythroleukemia (FAB classification M6). The kinetics of transferrin receptor cycle in bone marrow erythroblasts was obtained by pulse-chase experiments before the initiation of therapy. Internalization of transferrin was impaired and resulted in a delayed peak of internalized transferrin, as compared with the kinetics pattern seen in healthy subjects. The subsequent exocytosis of the internalized ligand was also delayed. Thus, transferrin receptor cycle seems to be influenced all along the transferrin pathway, hence transferrin travels more slowly in erythroblasts in erythroleukemia. The altered transferrin receptor cycle led to a diminished iron uptake per surface transferrin receptor (approximately 30% of that in healthy subjects), and the incorporation of iron into heme was greatly reduced. Our observations suggest a possible role for the altered transferrin receptor cycle in the pathogenesis of defective heme synthesis and ineffective erythropoiesis in erythroleukemia.

Endocytosis↗
PubMed1987

Erythroblast transferrin receptors and transferrin kinetics in iron deficiency and various anemias.

To clarify the role of transferrin receptors in cases of altered iron metabolism in clinical pathological conditions, we studied: number of binding sites; affinity; and recycling kinetics of transferrin receptors on human erythroblasts. Since transferrin receptors are mainly present on erythroblasts, the number of surface transferrin receptors was determined by assay of binding of 125I-transferrin and the percentage of erythroblasts in bone marrow mononuclear cells. The number of binding sites on erythroblasts from patients with an iron deficiency anemia was significantly greater than in normal subjects (p less than 0.01). Among those with an aplastic anemia, hemolytic anemia, myelodysplastic syndrome, and polycythemia vera compared to normal subjects, there were no considerable differences in the numbers of binding sites. The dissociation constants (Kd) were measured using Scatchard analysis. The apparent Kd was unchanged (about 10 nmol/L) in patients and normal subjects. The kinetics of endocytosis and exocytosis of 125I-transferrin, examined by acid treatment, revealed no variations in recycling kinetics among the patients and normal subjects. These data suggest that iron uptake is regulated by modulation of the number of surface transferrin receptors, thereby reflecting the iron demand of the erythroblast.

Anemia↗
PubMed1985

Disturbed prolactin responses to dopamine-related substances in patients with acromegaly and hyperprolactinemia.

We undertook this study, because conflicting data were reported about the dopaminergic regulation of prolactin (PRL) secretion in patients with acromegaly and hyperprolactinemia. In order to clarify the dopaminergic regulation of PRL secretion in patients with acromegaly and hyperprolactinemia, the effects of nomifensine, a central dopamine agonist, FK 33-824, a centrally antidopaminergically acting agent, and domperidone, a peripheral dopamine antagonist, on plasma PRL in these patients were studied. The results were compared with those observed in normal subjects and hyperprolactinemic patients, with or without a pituitary tumor. Nomifensine did not lower the PRL levels and FK 33-824 did not raise the PRL levels in acromegalic patients. In hyperprolactinemic patients, nomifensine did not lower the PRL levels and FK 33-824 failed to raise the PRL levels. Domperidone did not increase PRL in about a third of acromegalic patients, while TRH increased PRL in the all normoprolactinemic acromegalic patients. These results suggest that in acromegalic patients there may be a disturbance in dopamine related neurotransmission and that such disorders also seem to be present in patients with hyperprolactinemia, with or without a pituitary tumor.

Acromegaly↗
PubMed1983

[The age-related changes in serum 17-hydroxyprogesterone secretion in men].

In order to clarify the age-related changes in serum 17-hydroxyprogesterone (17-OHP) secretion in men, serum basal 17-OHP levels were determined in 203 healthy male subjects from 10 months to 116 years of age, and serum 17-OHP responses to dexamethasone (Dex), fluoxymesterone (FM), HCG and ACTH were compared between the young and elderly groups. The mean basal 17-OHP level remarkably increased from pubescence to the third decade and gradually decreased with advance in age after fifty. Basal serum 17-OHP level was correlated more closely with serum testosterone (T) than cortisol (F), and was suppressed more remarkably after the administration of FM than Dex in both groups. Serum 17-OHP increased with 2 peaks at 6 and 24 hours after HCG injection, and serum 17-OHP response to HCG was significantly greater in the young than in the elderly group. Furthermore, in the aged subjects with low serum T levels, serum 17-OHP response to HCG was remarkably decreased. Within 3 hours after ACTH injection, serum 17-OHP response to ACTH was significantly lower in the elderly than in the young group. On the other hand, 12 hours after ACTH administration, serum 17-OHP response was remarkably greater in the elderly group, and the F/17-OHP ratio was significantly lower than in the young. These data indicate a decline of Leydig cell function in the testis of the elderly male and also suggest the occurrence of enzyme deficiencies, especially impaired C17, 20 lyase activity, in adrenal steroid hormone synthesis with aging.

17-alpha-Hydroxyprogesterone↗
PubMed1982

Effect of vitamin E on function of pituitary-gonadal axis in male rats and human subjects.

The role of vitamin E in the endocrine system, in particular the pituitary-gonadal axis, was studied in humans and male rats by examining the hormonal differences between vitamin E deficient and supplemented conditions. In vitamin E deficient rats, pituitary content and basal plasma level of FSH and LH were significantly lower than those of the control rats, but testicular content and basal plasma level of testosterone were not significantly changed. On the other hand, in vitamin E supplemented rats, FSH and LH content in pituitary tissue was significantly higher than that of the controls, but there was no significant rise in basal FSH and LH level in plasma. The testosterone level was significantly elevated in both testicular tissue and plasma. It was also demonstrated that basal plasma testosterone and F.T.I. were increased in normal male subjects following oral vitamin E administration and the responsiveness of plasma testosterone levels to HCG was significantly higher during vitamin E administration than before administration. These results suggest that vitamin E may play an important and potent role in hormone production in the pituitary-gonadal axis in humans and rats.

Animals↗