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Biomedical subjects

K Hirashima

Publications and source records attributed to K Hirashima.

At least 127 records · Page 7Linked to original sources
PubMed1985

General pharmacological studies of hydroxypropylmethylcellulose acetate succinate in experimental animals.

Extensive general pharmacological studies of hydroxypropylmethylcellulose acetate succinate (HPMCAS) were carried out in mice, rats, guinea pigs, rabbits, dogs and frogs. HPMCAS appeared to have no significant effect on the central nervous system, autonomic nervous system and cardiovascular system. Various biological analyses of the blood (including hemolysis and coagulation properties) and urine were unaffected, and the compound showed no significant local anesthetic or vascular permeability. At higher doses of HPMCAS, an increase in secretion of saliva in guinea pigs, a decrease in gastric juice secretion in rats and an increase in rectal temperature in rats were observed, but these effects did not show clear dose-dependence.

Animals↗
PubMed1985

Toxicological studies of hydroxypropylmethylcellulose acetate succinate--acute toxicity in rats and rabbits, and subchronic and chronic toxicities in rats.

The acute toxicity (in rabbits and rats) and the subchronic and chronic toxicities (in rats) of Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a potentially useful pharmaceutical excipient, were investigated. 1) In the acute toxicity study (single oral dose of 2.5 g/kg), no deaths or behavioral abnormalities were observed. Thus, LD50 is higher than 2.5 g/kg. 2) In the subchronic toxicity study (0.63, 1.25 or 2.5 g/kg daily as a single oral dose in the morning, 6 days per week (not Sunday) for 2 months), no significant behavioral abnormality was observed. There was some decrease in body weight gain in rats of both sexes, but the effect was not statistically significant. 3)In the chronic toxicity study (1.25 or 2.5 g/kg daily as a single oral dose in the morning, 6 days per week (not Sunday) for 6 months), no significant behavioral abnormality was observed. There was some decrease in body weight gain in male rats, but it was not statistically significant. 4)Various biochemical and physiological abnormalities in rats were noted in all groups (including the control groups) in the toxicity studies, but there appeared to be no significant dose-related finding attributable to the administration of HPMCAS.

Administration, Oral↗
PubMed1984

Relationship between fibroblastoid colony-forming units (CFU-f) and hemopoietic precursor cells in normal human bone marrow.

To clarify the relationship between fibroblastoid colony-forming units (CFU-f) and hemopoietic precursor cells, simultaneous assays of CFU-f, CFU-e, BFU-e, and CFU-c from the bone marrow of 10 healthy volunteers were performed. The number of CFU-f correlated positively with CFU-e (r = 0.905, P less than 0.001) and BFU-e (r = 0.842, P less than 0.005), but not with CFU-c (r = 0.530, P greater than 0.1). These findings support the hypothesis that CFU-f is related to erythropoiesis in the steady state of hemopoietic tissue. Further studies of the relationship between CFU-f and erythroid precursor cells in patients with hematological diseases may help clarify their pathophysiology.

Adult↗
PubMed1984

Reduction of granulocyte-macrophage progenitor cells (CFU-C) and fibroblastoid colony-forming units (CFU-F) by leukemic cells in human and murine leukemia.

The number of bone marrow granulocyte-macrophage progenitor cells (CFU-C) and fibroblastoid colony-forming units (CFU-F) was significantly smaller in acute leukemia patients. To analyze the mechanism by which CFU-C and CFU-F were reduced, the study on murine myeloid leukemia was carried out. In murine leukemia, bone marrow CFU-C and CFU-F decreased in number in correlation with the proliferation of leukemic cells. Murine leukemic cells suppressed the growth of CFU-C and CFU-F in the mixed culture of leukemic cells and normal murine marrow cells. Furthermore, leukemic cell-conditioned medium inhibited the growth of CFU-F. The results show that murine leukemic cells themselves and/or humoral factors produced by them give inhibitory effects on the growth of not only CFU-C but also CFU-F.

Animals↗
PubMed1984

Poor response of Wv/Wx mice to a grafted neutrophilia-inducing, colony-stimulating-factor-producing tumor.

Although mice possessing two mutant genes at the W locus have a defect in multipotential hematopoietic stem cells that form macroscopic colonies in the spleen of irradiated mice, the number of neutrophils in the blood of these mutant mice is normal or nearly normal. We investigated neutrophil production using the NFSA fibrosarcoma of C3H mouse origin, which induces neutrophilia accompanied by production of a neutrophil-macrophage colony-stimulating factor by the tumor. When the NFSA tumor was transplanted to (C57BL/6 X C3H/He)F1-Wv/Wx or to congenic +/+ mice, neutrophilia developed in mice of both genotypes. However, there was a significant difference between the degree of neutrophilia that developed in them; there was a 107-fold increase in the +/+ mice, but only a 28-fold increase in the Wv/Wx mice four weeks after tumor transplantation. This result is consistent with the concept that doubly heterozygous W mice have multipotential stem cells with diminished ability to respond to stimulation. The unperturbed condition may not provide a sufficient stimulus to demonstrate the defect in neutrophil production in doubly heterozygous W mutant mice.

Anemia↗
PubMed1984

Stimulation of human and murine bone marrow cell colony formation by colony-stimulating factors obtained from the urine of mice bearing leukocytosis-inducing fibrosarcoma.

Dialyzed urine of mice bearing leukocytosis-inducing fibrosarcoma stimulated granulocyte colony formation in semisolid agar culture of human bone marrow cells. Removal of phagocytic cells prior to stimulation did not interfere with the formation of these colonies in the culture. On the other hand, macrophage colonies were predominantly produced when murine bone marrow cells were stimulated by the dialyzed mouse urine. The activity of colony-stimulating factor (CSF) in the urine of normal mice was less than 1/100 of that in the urine of tumor-bearing mice. DEAE-cellulose column chromatography separated the activity stimulating human granulocyte colony formation from that stimulating murine macrophage colony formation. Further purification showed that a sialoglycoprotein with an apparent molecular weight of 80,000 corresponded to the macrophage CSF, which was devoid of activity toward human cells. The molecular properties of the human-active granulocyte CSF could not be studied further, because it was quite unstable.

Animals↗
PubMed1984

Single cell origin of radiation-induced thymic lymphoma in mice with cellular mosaicism.

The clonal origin of radiation-induced thymic lymphoma was studied in mice with cellular mosaicism for phosphoglycerate kinase (PGK). Repeated whole-body X-irradiations (4 doses, 1.7 Gy each) with intervals of 7 days resulted in development of thymic lymphomas in the mosaic mice. PGK from all lymphomas gave only a single spot on electrophoresis. The results demonstrate the single cell origin of the thymic lymphoma.

Animals↗
PubMed1984

Macrophage colony-stimulating factor and granulocyte colony-stimulating factor separated from fibrosarcoma tissue in mice.

Large increases of granulocytes and monocytes were found in the blood of mice bearing fibrosarcoma. Extraction of the tumor tissue with isotonic saline yielded a colony-stimulating factor (CSF). Further extraction of the saline-insoluble materials with 0.1% sodium dodecyl sulfate afforded another pool of CSF. Incubation of the tumor cells in vitro resulted in the accumulation of CSF activity in the culture medium. The CSF from these sources produced both granulocyte colonies and macrophage colonies in murine bone marrow cell culture. Subsequently, the activity producing granulocyte colonies was separated from that producing macrophage colonies by isoelectrofocusing and repeated gel-filtration chromatography. It was also shown that anti-L cell CSF antiserum neutralized the macrophage CSF activity but not the granulocyte CSF activity. These results show that the granulocytosis-inducing tumor produces two types of CSF.

Animals↗