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T Murohashi

Publications and source records attributed to T Murohashi.

16 recordsLinked to original sources

Immunotherapeutic trials of murine and guinea-pig solid tumors by oral administration of BCG.

Efficacy of oral administration of BCG on the growth of various tumors in mice and guinea pigs was studied. The growth-inhibitory effect varied depending on the tumor systems and the experimental conditions. Weekly oral administrations with 5-mg doses of BCG to mice or 80-mg doses of BCG to guinea pigs were ineffective on syngeneic mouse melanoma B16 or syngeneic guinea pig hepatocarcinoma line-10 but effective on syngeneic mouse carcinoma IMC and syngeneic guinea-pig fibrosarcoma H9A. Oral BCG seemed effective also on allogeneic mouse carcinoma Ehrlich, developed with a relatively small size of tumor cell inoculum, and on guinea-pig syngeneic liposarcoma H10. On Ehrlich tumors, oral BCG given once a week seemed to have better effects than did oral BCG given twice a week or subcutaneously once or repeatedly; heat-killed BCG given orally showed no effect. However, it seems premature to draw a definite conclusion on the efficacy of oral BCG on Ehrlich and H10 tumors, because some of these tumors regressed spontaneously even in nontreated control animals. The host responses to oral BCG were studied with the following results. Weekly oral administration with 80-mg doses of BCG to guinea pigs elicited positive skin reactions to 25 TU PPD in about 65 days after the first BCG, while a single sc injection of 8 mg of BCG did so within 10 days. Orally administered BCG organisms were recovered largely from Peyer's patches, a little from the mesenteric lymph nodes, and very little from the liver and the spleen. The BCG distributive pattern was in reverse order when BCG was given subcutaneously. Histologic examinations of Peyer's patches indicated enlargement of germinal centers, in which primitive reticular cells proliferated prominently and the macrophages with tingible bodies scattered frequently.

Administration, Oral

Mouse-strain difference in immunoprophylactic and immunotherapeutic effects of BCG on carcinogen-induced autochthonous tumors.

The prophylactic and therapeutic effects of BCG on the tumors induced by 3-methylcholanthrene (MCA) were studied comparatively between two inbred mouse strains, SWM/Ms and C3H/He, the first tumor appeared 5 weeks after MCA and the cumulative tumor incidence reached almost 100% within 20 weeks. On the other hand, the first tumor appeared 8 weeks after MCA in SWM/Ms, the number of tumor-bearers increased more slowly than in C3H/He, and the final tumor incidence (at 30 weeks) was about 90-80%. Single subcutaneous injection with BCG 2 weeks prior to MCA significantly protected SWM/Ms from tumor development, but not in C3H/He. These tumors, once appeared grew progressively and killed the hosts equally in both the strains. Intratumor (i.t.) injection with BCG showed more or less therapeutic effects in SWM/Ms; most tumors regressed or retarded after BCG. The time period after tumor-appearance to tumor-death was prolonged in most of SWM/Ms mice given i.t. injection with BCG, except a few mice that died earlier than non-treated controls after BCG. Contrary, no therapeutic effect of i.t. injection with BCG was observed in C3H/He. different host responses to BCG between SWM/Ms and C3H/He were found by the peritoneal macrophage disappearance test and the footpad reaction test; SWM/Ms was a high-responder to BCG and C3H/He was a low-responder. The marked differences between SWM/Ms and C3H/He in prophylactic and therapeutic effects of BCG on the autochthonous tumors were discussed in terms of difference of the host immune response to BCG that is defined genetically.

Animals

Responses of tumors induced in inbred guinea pig strain JY=1 and strain Hartley/F to BCG.

A transplantable fibrosarcoma induced in inbred JY-1 guinea pig strain by 3-methylcholanthrene (MCA) and designated J4, an allotransplantable subline of J4 (JH4) which was obtained by the transplantation of J4 into the inbred Hartley/F guinea pig strain and maintained by passages in this strain, and a syngeneic liposarcoma H10 induced in a Hartley/F guinea pig by MCA were tested for their immunotherapeutic response with BCG. The growth of J4 and H10 tumors was suppressed in most of the animals when tumor cells were mixed with BCG before being injected sc into BCG-immune or BCG-nonimmune recipients. The growth of the JH4 tumor was suppressed at the sites of injection with a mixture of tumor cells and BCG in BCG-immune recipients but not in nonimmune animals. All guinea pigs surviving the injection of a tumor cell-BCG mixture resisted a second tumor cell challenge. When subcutaneous sarcomas grew to about 8-15 mm in diameter, BCG was injected into the tumors. The growth of JH4 tumor was not influenced by the injection in either BCG-immune or BCG-nonimmune animals, while the regression of the established J4 transplants was produced in 2 of 3 nonimmune recipients. The growth of the H10 tumor was not inhibited with an intratumor injection into nonimmune guinea pigs, while the H10 tumor regressed in BCG-immune animals for 4-5 weeks after intratumor injection and thereafter grew progressively. Skin reactions in animals that received repeated intradermal injections of the tumor cells and BCG were tested with 10(6) viable tumor cells as eliciting antigens. Typical delayed-type hypersensitivity reactions that were specific to the homologous antigens were observed. The possible reasons for the different responses to BCG among the guinea pig tumors, including line-10 hepatocarcinoma in strain-2 guinea pigs, were discussed.

Animals

Atrial myxoma associated with multiple hamartomas.

A case of cardiac myxoma associated with renal angiofibrolipomas, renal medullary fibromas, thyroid adenoma and jejunal polyp was presented. So far as we know, the combined form of cardiac myxoma and renal hamartoma has not been hitherto reported. The combination of these various complications may suggest the relationships of tuberous sclerosis, Cowden disease, lymphangiomatosis among others. Besides it is noteworthy that the three of them, i.e. cardiac myxoma, renal angiofibrolipomas and thyroid adenoma, presented considerable atypism at the same time. As to the histogenesis of cardiac myxoma, this case may be in accord with the hamartoma theory.

Autopsy

World Health Organization studies on bacteriophage typing of mycobacteria. Subdivision of the species Mycobacterium tuberculosis.

The ability of lytic mycobacteriophages to subdivide the species Mycobacterium tuberculosis reliably has been studied using a series of 100 strains isolated from cases of tuberculosis in the Netherlands. Techniques for the propagation and application of the viruses have been standardized, as have the conditions for growth and preparation of bacterial strains. On the basis of lytic results with 11 mycobacteriophages, it is proposed that the species Mycobacterium tuverculosis may be subdivided into at least 3 major phage types, A, B, and C, and into 2 subjects, Ax and A2. The reliability of the individual bacteriophage lytic result has been assessed, and the relationship between phage reliability and the degree of certainty with which a strain may be assigned to a phage type is described. The effect of rigorous standardization of techniques on the reliability of bacteriphage typing is demonstrated, and a standard protocol is proposed.

Bacteriophage Typing

Stimulating effect of leucine on the growth of M. leprae.

M-Y 16j agar slant was prepared by modifying M-Y 14b which has hitherto been used most widely in our experiments by increasing the amount of Na pantothenate and adding leucine, and the growth stimulating effect was investigated referring to the foregoing subculture experiments. The results revealed that the growth of M. leprae was stimulated remarkably in the primary isolation quite similarly to the subculture. This seemed to be resulted from stimulated biosynthesis of fatty acids by the leucine metabolism. The authors are greatly indebted to the World Health Organization and the Comité Exécutif International pour l'Assistance aux Lépreux for their financial support and to Dr. S. Ishihara, the Director of the National Suruga Leprosarium, for his kind supply of the materials to be cultured and for the lepromin test in leprosy patients carried out by himself. The main point of this study was presented to the 50th Annual Meeting of the Japanese Leprosy Association.

Agar

Isolation of M. leprae using semi-synthetic solid agar medium.

The primary isolation of M. leprae from leprous nodules was carried out using agar slant prepared by solidifying the basic compositions of M-Y series to confirm the reproducibility of the preliminary studies. Results revealed that L-Feb-75 strain represented thin membraneous growth from about 20th week and it crept up the culture tube wall at about 30th week of incubation at 37 degrees C. L-Jun-75 strain, on the other hand, exhibited numerous, white and rough colonies of submiliary size on various places of the lustreless, thin membraneous structure at the inoculation site. Thus, it was clearly demonstrated again that M. leprae could be isolated very well on the surface of agar slant of M-Y series. It is very interesting bacteriologically to note that L-Feb-75 strain formed wrinkled thin pellicle floating on the surface of liquid medium. Further, the fact that L-Jun-75 strain was isolated from a leprous nodule preserved for more than 3 months at -20 degrees C was very suggestive indicating a standard for the preservation conditions of pathological materials for at least 3 months from removal to cultivation without destroying the viability of M. leprae contained.

Agar

Drug sensitivity of M. leprae isolated from leprosy patients administered DDS for long period of time.

Drug sensitivity was tested using liquid medium on three stains isolated from the subcutaneous nodules of L-type patients who have long been administered DDS alone. The results revealed that the first strain was resistant to DDS up to the concentration of 1.0 microgram/ml suggesting as if it were DDS dependent or enhanced strain, whereas the second strain was completely sensitive to DDS even at the lowest concentration of 0.01 microgram/ml suggesting possible inactivation of this drug in the host patient. The third strain was completely resistant to 0.1 microgram/ml, but sensitive to 1.0 microgram/ml of DDS, suggesting that the therapeutic effect can not be expected any more, when the strain becomes resistant to 0.1 microgram/ml of DDS. All of the three strains were sensitive to REP at the concentration of 0.01 microgram/ml, and the host patients of the former two strains showed rapid improvement of the clinical symptomes after REP administration. That the second strain was sensitive to INH at the concentratin of 0.01 microgram/ml suggested the availability of the combined use of INH in the chemotherapy of leprosy.

Dapsone