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Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 451 records · Page 25Linked to original sources
PubMed1982

Occurrence of drug resistance in human tumor implanted in nude mice.

A line of human breast tumor xenograft in nude mouse, MX-1, acquired resistance to vincristine or mitomycin C during multiple treatments; both drugs were effective against the parent line of this tumor. If the treatment was started when the tumor was smaller than 500 mm3 in size, MX-1 was responsive to the initial treatment with vincristine (0.8 mg/kg) or mitomycin C (3.4 mg/kg), and some animals survived with complete regression of the tumor. However, some of the recurrent tumors were able to tolerate multiple treatments with either of these agents, and finally acquired apparent resistance to the agent. On the other hand, when tumors larger than 5,000 mm3 were treated with vincristine, the occurrence of resistance was observed with much higher frequency than when small tumors were treated. Resistant tumors thus obtained exhibited significant refractoriness to each agent when they were reimplanted in new mice and treated in the same manner. This suggests that the occurrence of resistance can be ascribed to changes not in metabolic functions of the host animal but in the tumor cell populations.

Animals↗
PubMed1982

Biochemical characteristics of a 5-fluorouracil-resistant subline of P388 leukemia.

A 5-fluorouracil (5-FU)-resistant cell line of P388 mouse leukemia was established by intraperitoneal treatment with the drug. The activities of enzymes responsible for the formation of 5-fluoro-2'-deoxyuridine 5'-monophosphate and 5-fluorouridine 5'-monophosphate from 5-FU, the quantities of 5-FU metabolites, and the permeability to 5-FU were determined in both the 5-FU-sensitive and the resistant cell lines. It was found that the activities of uridine kinase and uracil phosphoribosyltransferase, the initial uptake of 5-FU, and the intracellular levels of 5-FU-nucleotides were all decreased in the resistant cells. However, the initial uptake of 5-FU into cells preincubated with KCN was the same in the sensitive and the resistant cells. These results support the view that the ineffectiveness of 5-FU against the resistant cell line of P388 leukemia can be attributed to decreases in the activities of enzymes responsible for the formation of 5-FU-nucleotides and probably also decreased transport of 5-FU in the resistant cells.

Animals↗
PubMed1981

Regeneration of axillary hairs after plucking.

Studies on the regeneration of axillary hairs after plucking are described. Regeneration of axillary hairs after plucking was recognized as originating in a special region of the upper isthmus of the hair apparatus, from which point solid pegs of epithelial cells grow downward and form inner root sheaths. New hairs form in their centers. At this stage, the lower parts of the hair follicles descend while the new hairs grow from the centers of the pegs by vigorous mitosis of germinal cells. Eventually, the epithelial cells wrap around masses of mesenchymal cells and form new bulbs from which hair shafts grow upward. The new matrices acquire new complements of functioning melanocytes.

Axilla↗
PubMed1981

Clinical observations on the development and eventual character of hair in the axillae of human beings.

The authors examined clinically growth and patterns of axillary hair of Japanese males and females of various ages with a specific interest in the differences between vellus and coarse hairs. One notable finding was that in the axillae of children, vellus hairs are equidistant and solitary, whereas the coarse hairs that replace them emerge during puberty as solitary hairs and in bundles or groups. A statistical summary and speculation as to why growth of vellus hair and growth of coarse hair differ are the substance of this report.

Adolescent↗
PubMed1981

Effects of adrenal demedullation and peripheral noradrenaline-depleting agents on adrenocortical function and spleen in rats.

Adrenocortical functions of adrenal-demedullated rats (ADMx rats) and peripherally chemical-sympathectomized ADMx rats were studied by examining changes in the levels of serum and adrenal corticosteroids (CS). Resting levels of serum and adrenal CS were not influenced by adrenal-demedullation and peripheral chemical-sympathectomy with 6-hydroxydopamine. Diurnal variation in serum CS concentration was also unchanged, suggesting that peripheral adrenergic systems do not influence the basal function of hypothalamo-pituitary-adrenocortical axis. Exposure of ADMx rats to the stressful stimuli, however, resulted in lowered adrenocortical response with a lesser increase in serum CS concentration, while peripheral chemical-sympathectomy of ADMx rats with 6-hydroxydopamine or guanethidine caused a significant enhancement of adrenocortical response to the stress with elevation of the serum CS concentrations. These findings suggest that increased peripheral adrenergic activity may suppress the activation of the hypothalamo-pituitary-adrenocortical system as the animals were exposed to the stressful stimuli. Adrenal-demedullation produced no increase in spleen weight while chemical-sympathectomy by peripheral administration of 6-hydroxydopamine did produce a significant increase in the weight of this organ. Histological features following chemical-sympathectomy are described.

Adrenal Cortex↗
PubMed1981

Antitumor activity of 7-n-(p-hydroxyphenyl)-mitomycin C in experimental tumor systems.

The antitumor activity of 7-N-(p-hydroxyphenyl)-mitomycin C (M-83) was compared with that of mitomycin C (MMC) in rodent tumor systems. M-83 exhibited more potent activity than MMC against the ascitic form of lymphocytic leukemia P388 and fibrosarcoma Meth 1, and doses of over 5 mg/kg of M-83 (1/6 LD50) resulted in some 60-day survivors. The chemotherapeutic ratio (optimal dose/MED) of M-83 was around 64 and was estimated to be approximately 5 to 8 times higher than that of MMC. Upon intravenous administration, M-83 also gave a better survival and showed a higher chemotherapeutic ratio than MMC against intravenously implanted P388. M-83 inhibited the growth of solid form of sarcoma 180 to the same extent as MMC at an equivalent dose, but showed a higher safety margin than MMC. M-83 was as effective as MMC against Lewis lung carcinoma at dose levels giving the same degree of toxicity. In vitro studies on tumor growth inhibition demonstrated that the cytotoxic effects of M-83 against leukemia P388 and fibrosarcoma Meth 1 cells were similar to and stronger than those of MMC, respectively.

Animals↗
PubMed1981

Comparison of the hematologic toxicity of 7-N-(p-hydroxyphenyl),-mitomycin C and mitomycin C.

7-N-(p-Hydroxyphenyl)-mitomycin C (M-83), a new analog of mitomycin C (MMC) with equivalent or greater antitumor potencies against various experimental tumors, was investigated to determine its hematologic toxicity in mice. M-83 showed a significantly lower toxicity than MMC with respect to myelosuppression and leukopenia when compared at equivalent effective doses. In M-83-treated mice, the damage to the bone marrow was much milder at the nadir point and the recovery from myelosuppression to the normal level was faster as compared with that in the case of MMC. As a result, the number of white blood cells in the peripheral blood of the M-83-treated groups was considerably greater than that in the MMC-treated ones. These findings suggest that M-83 may be effective in clinical use.

Animals↗
PubMed1981

Mechanism of natural resistance to vincristine in rat ascites hepatoma AH66.

It was found that AH66, a rat ascites hepatoma inherently refractory to vincristine, exhibited definite resistance to a different class of antitumor agents- adriamycin and actinomycin D. In comparative studies with AH13, a sensitive strain of rat hepatoma, significantly lower levels of cellular retention as well as uptake of these drugs were observed with AH66 cells. However, in the presence of 2, 4-dinitrophenol in glucose-free medium, the uptake of vincristine by AH66 cells was remarkably increased, and addition of glucose induced a spontaneous efflux of drug that had been taken up. These results, in good accord with those for a subline of P388 mouse leukemia which acquired resistance to either adriamycin or vincristine, suggest that there exists an active efflux system common to these different kinds of antitumor agents in naturally resistant rat tumor cells. Further studies revealed that Tween 80 also enhanced the uptake of vincristine by AH66 cells by interfering with the efflux of this drug and thus partially restored the sensitivity in vitro of AH66 cells to vincristine.

2,4-Dinitrophenol↗
PubMed1981

Preferential action of liposome-entrapped 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea on lung metastasis of Lewis lung carcinoma as compared with the free drug.

Lipid vesicles entrapping a lipophilic antitumor agent, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU), within the membrane phase were prepared and their antimetastatic activity was compared with that of free MeCCNU using intravenously inoculated Lewis lung carcinoma. It was found that the liposome preparation exhibited more potent inhibitory activity than the free drug on colony formation in the lung, when administered intravenously as well as intraperitoneally. Superior life-prolongation effect was also observed with liposome preparations as compared with the free drug in this system. However, the two forms of MeCCNU showed almost the same activity against not only Lewis lung carcinoma but also P388 leukemia inoculated subcutaneously and intraperitoneally, respectively. These results suggest that the superior effect of liposome-entrapped MeCCNU on lung metastasis might be due, at least in part, to preferential distribution of liposomes to the lung as compared with the free drug.

Animals↗
PubMed1980

Antitumor activities of newly synthesized 5-carbamoyl-1 H-imidazol-4yl 1-adamantanecarboxylate and 5-carbamoyl-1H-imidazol-4yl piperonylate.

In synthetic studies on the chemical modification of the nucleoside antibiotic bredinin, two new derivatives, 5-carbamoyl-1H-imidazol-4-yl 1-adamantanecarboxylate and 5-carbamoyl-1H-imidazol-4-yl piperonylate, were found to possess a potent antitumor activity in several experimental tumor systems, even though bredinin itself shows only in vitro cytotoxicity and thus lacks therapeutic effectiveness. These two derivatives of bredinin exhibited antitumor activity against a wide variety of tumors, including leukemias L1210 and P388, Lewis lung carcinoma, B16 melanoma, Colon 26 and 38 adenocarcinomas. Ehrlich carcinoma, and Sarcoma 180. It is noteworthy that these agents showed good therapeutic effects not only against ascitic types of tumors but also against a number of slow-growing solid tumor lines, particularly the ascitic and solid forms of Ehrlich carcinoma. At their optimal doses, both compounds effected a complete cure of all or most of the mice treated. Although the mechanisms of action of these compounds remain unknown, they are able to suppress in vivo tumor growth, presumably by being slowly anabolized in vivo to an active form and inhibiting purine de novo synthesis as bredinin does.

Animals↗
PubMed1979

Enhanced efflux of actinomycin D, vincristine, and vinblastine in adriamycin-resistant subline of P388 leukemia.

In vitro cross-resistance of adriamycin-resistant subline of P388 leukemia to non-anthracycline agents-actinomycin D, vincristine and vinblastine was elucidated. Decreased uptake of these 3 drugs was observed with the resistant cells. In addition, 2,4-dinitrophenol, a metabolic inhibitor, greatly enhanced the uptake of these drugs by the sensitive and resistant cell lines, particularly by the latter, abolishing a difference in drug uptake between the 2 which was observed under the normal condition. These results suggest that adriamycin-resistant cells are endowed with an enhanced capacity for outward transport of not only anthracycline antibiotics, but chemically and pharmacologically dissimilar agents such as the aforementioned agents.

Animals↗
PubMed1979

Synthesis and antibacterial activity of 2'-substituted chelocardin analogues.

Chelocardin (1) was condensed with numerous hydrazines, hydrazides, and anilines, yielding 2'-substituted derivatives with antibacterial spectra similar to the parent antibiotic. The hydrazone derivatives 9 and 10 and the two anilino derivatives 42 and 44 had more in vivo antibacterial activity than chelocardin.

Animals↗
PubMed1979

Histologic study of the regeneration of axillary hair after removal with subcutaneous tissue shaver.

It was observed that after subcutaneous tissue shaving for the radical therapy of hircismus and hyperhidrosis axillary hair often regrew. Histologic study of this phenomenon showed that hair bulb and most of the follicle up to a level near the sebaceous duct opening had been removed. Hair regrows from remnant outer root sheath, but only when sebaceous glands are preserved, that is when the upper portion of the follicular isthmus is intact. One or several solid epithelial pegs grow downward from the cut end of the trichilemma, and inner root sheath and new young hair are formed in its center. In hair peg stage, the lower tip of the hair follicle descends while new hair is growing in its center through the mitotic activity is growing in its center through the mitotic activity of hair germ cells and is prevented from pushing toward the skin surface by interlocking fusion between hair cuticula and sheath cuticula. Eventually, the epithelial cells wrap around a mass of mesenchymal cells and form a new bulb from which the terminal hair grows upward. The new matrix acquires a new complement of functioning melanocytes.

Adult↗