Biomedical subjects
Publications and source records attributed to H Shisa.
A case of pulmonary adenocarcinoma with numerous calcified metastatic nodules of the brain is reported. Autopsy revealed about 400 metastatic nodules in the central nervous system, most of which were calcified.
The gene dosage change of nucleolar cistrons (rDNA) in tumor cells has not been extensively studied. The present studies showed that increased dosage, as well as abnormal distribution of rDNA, was frequently associated with leukemia cells of SL/Ni and AKR mice. In normal SL cells, 37%, 39%, and 25% of rDNA was located in nucleolar organizer regions (NOR) of chromosomes #12, #18, and #19, respectively. Increase of rDNA/DNA was shown by hybridization on filter membranes in SL1, SL2, SL3, and M1 leukemia cells. Direct measurement of rDNA/DNA in G1 cells revealed an 11% increase in synchronized M1 cells. The increased rDNA dosage was explained by trisomy 12 in SL1 and SL2, the ectopic NOR of #9 in SL3, and the double t(X;19) marker chromosomes in M1. On the other hand, in normal AKR cells, 27%, 29%, and 45% of rDNA was assigned to NORs of chromosomes #15, #16, and #18, respectively. The relative rDNA distribution among NORs estimated by autoradiographic grain counting was suggested to be abnormal in AKR leukemia cells despite their normal karyotype; 36% rDNA was shown to be in chromosomes #15 and #16, respectively, by relative reduction in chromosome #18 in AKR1; the trisomy 15 explained the increased rDNA in AKR2; a relative increase was found in chromosome #15 in AKR3. These results were discussed with reference to the reported NOR involvement in chromosome translocation and amplification in tumor cells.
The effect of nude gene heterozygosity on spontaneous AKR thymic lymphomagenesis was studied by comparing female littermates of AKR/Ms-nu/+ and +/+. As previously reported in nude gene heterozygotes with genetic background other than AKR, AKR/Ms-nu/+ mice had a significantly smaller thymus than the +/+ littermates. Overall incidences of thymic lymphomas were comparable in the two genotypes, but the mean latent period for lymphoma development was significantly shorter in the nu/+ mice (266.3 +/- 11.6 days) than in the +/+ mice (319.3 +/- 7.9 days). Both genotypes of mice expressed a high level of XC+-ecotropic murine leukemia virus. Expression of xenotropic virus was more variable, but there was no consistent difference in onset of virus expression or in virus titer that could explain accelerated lymphomagenesis in the nude gene heterozygotes.
The role of the thymus in propylnitrosourea (PNU)-induced thymic lymphomagenesis was studied in F344 rats with genetically determined high susceptibility. The thymus was absolutely required for thymic lymphomagenesis, since thymectomy prior to or after PNU treatment abolished lymphomagenesis, whereas grafting of a normal neonatal thymus before PNU treatment restored it. Exposure to PNU for 42 days resulted in the appearance of potentially lymphomatous cells first in the thymus, and overt T-lymphomas subsequently appeared. Such cells seemed to be thymus-dependent, since intrathymic transfer of the thymus cells from 42-day PNU-treated rats induced T-lymphomas much more efficiently than intravenous transfer. Further, grafting of the thymus from 42-day PNU-treated rats into thymectomized rats resulted in T-lymphomas of donor origin without additional PNU treatment. Cells from the spleen or bone marrow from the same donors did not give rise to T-lymphomas irrespective of the route of cell transfer and sublethal irradiation of the recipients. Morphologically atypical cell foci were detected first on the 28th day in the thymus and were most pronounced during the 35th-42nd days. Therefore, the thymus is the essential organ in which the early events of PNU-induced rat T-lymphomagenesis take place.
Administration of propylnitrosourea p.o. by our protocol induced a high incidence of hematolymphatic neoplasms in all six rat strains studied. Remarkable strain differences in susceptibility to thymic lymphomas were observed. The incidence of thymic lymphomas was high in Fischer 344 (98%) and Wistar/Furth (71%) but low in Sprague-Dawley (29%), ACI/Ms (23%), Donryu (24%), and Long-Evans (10%) strains. Segregation of thymic lymphoma incidence among crosses between highly susceptible Fischer and poorly susceptible Long-Evans rats indicated that the increased susceptibility to thymic lymphomas of Fischer rats was determined by a dominant gene TIs-1 (thymic lymphoma susceptible) and that this gene was linked to the coat color loci, p and c, in Linkage Group I in the order of TIs-1 - c - p. The presence of another independently assorting dominant gene, TIs-2, was also suggested to accelerate the thymic lymphoma-genesis. Expression of the group-specific antigen of murine leukemia virus as well as infectious viruses was not detected in nine propylnitrosourea-induced thymic lymphomas of Fischer rats.
Developing thymic leukemias of the mouse have been assumed to form symbiotic complexes with thymic microenvironments. This symbiosis is morphologically based on pseudoemperipolesis (PEMP). The mechanism of the association of microenvironment-dependent leukemia cells with thymic epithelial reticular cells (TER) was analyzed in vitro by scanning electron microscopy, microcinematography, and a quantitative assessment of PEMP. PEMP was a consequence of active locomotion of the leukemia cells, with TER passively accepting the leukemia cells "crawling" under their cytoplasm. The integrity of the cytoskeletal system of both cells was essentially required for PEMP, since cytochalasins and colchicine were highly inhibitory to PEMP. The mechanism of action of these compounds was probably dual: inhibition of the locomotive movements of the leukemia cells. A similar inhibition of PEMP was also observed with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.
A new human cell line, Br-NHF-1, was established from the pleural effusion of a patient with advanced mammary carcinoma. The cells survived 52 subcultivations during more than 33 months. The cells possess epithelial features, showing rosettes, acinar formation and domes in or among the compact colonies. The modal chromosome number is 51 with some marker chromosomes. Xenografted tumors retained a similar histology to the original tumor. No estrogen-binding protein was detectable in the culture, but there was a significant amount of basic fetoprotein. Production of casein in the cells was detected by immuno-fluorescence testing.
Early changes in the esophageal mucosa of dogs induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) were studied. Seven one-year-old beagle dogs were given a solution of 250 micrograms ENNG/ml to drink ad libitum for 4 months. Three different kinds of lesions (10 erosive carcinomas, 4 slightly elevated microcarcinomas and 19 leukoplakias) were recognized. These three kinds of lesions were not located adjacent to one another, and were surrounded by almost normal stratified squamous epithelium. The foci of the carcinomas revealed an abrupt transition to normal epithelium and were considered to have arisen abruptly from normal esophageal epithelium. The histogenesis of squamous cell carcinomas of the esophagus in dogs may differ from that in man.
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The leukaemogenic effect of N-butyl-N-nitrosourea (BNU) was studied in normal and thymectomized AKR mice which were lethally irradiated and restored with either bone-marrow (BM) or spleen cells from (AKR X AKR/T1ALD)F1 donors. In some instances T1ALD thymic cells were added to the restorative inoculum. It was possible to determine the origin of the leukemic cells by the metacentric marker chromosomes of T1ALD. The T- or B-cell characteristics were further ascertained by the cytotoxicity test for theta antigen and the EAC rosette test. All leukaemias whether thymic (TLS) or extra-thymic (ETL), developed from donor bone-marrow or spleen cells and never from the injected thymic cells. In non-thymectomized animals BNU increased the percentage of TLS and shortened their latency. Most of TLS which occurred after BNU treatment of BM-restored mice were theta-negative whereas the majority of TLS which occurred in controls and in spleen-restored animals were theta-positive. This suggests that during their maturation process BM-derived T precursors transit through a theta-negative compartment. This compartment does not reach a similar size during the maturation process of the spleen-derived precursors. Adding thymic cells to the restorative inoculum enhanced leukaemogenesis and suppressed theta-negative TLS in BM-restored mice. Thymectomized mice, restored either by BM or spleen, had a low incidence of ETL which was not significantly increased by BNU treatment except in the case of mice restored with spleen cells. The leukaemic cells of one ETL were theta-positive whereas all the other leukaemias had no detectable T or B marker. The percentage of ETL was higher in thymectomized mice treated with BNU alone than in those previously subjected to irradiation and restoration. These results strongly suggest that a theta-negative T precursor could be involved in extra-thymic leukaemogenesis but the possible involvement of a B precursor cannot be rule out unless experiments are carried out with specific markers of T- and B-cell sub-classes.
Karyotype difference between the AKR/TIALD strain (T1) that bears 2 metacentric markers, and the AKR strain (no marker) was used to follow the thymic repopulation of lethally irradiated (AKR X T1) F1 hybrids restored by AKR bone marrow (BM) or spleen cells. Eleven days following radiation exposure, 40-50% of the thymic cells were BM-derived in the mice restored with BM cells whereas spleen-derived cells remained below 10% in those restored with spleen cells. The thymic repopulation by spleen-derived elements was enhanced either by injecting a larger munber of spleen cells or by adding thymic cells to the spleen inoculum; however in both cases the appearance of the spleen-derived karyotypes still required a delay of about 11 days. The thymic cells could either recruit thymic precursor cells or trigger their multiplication. On the opposite, it has not been possible to demonstrate a favorable effect of the injected thymic cells on the repopulation of the thymus by BM-derived elements.
Administration of N-butylnitrosourea (BNU) induces leukemia in thymectomized C57BL/6J and C3Hf/Bi mice with almost the same high frequency as in non-thymectomized mice. Thymectomized and BNU-treated (C3Hf/Bi times CBA/H-T6T6)F1 mice receiving neonatal thymus tissues from C3Hf donors developed leukemias with or without marked enlargement of the grafts. The origin of leukemic cells was analysed by T6 marker chromosome and thymus allo-antigen theta in this hybrid system. Cells from leukemia with enlarged thymus grafts possessed the sigma-antigen detected by cytotoxicity tests. Cells from leukemia without thymus involvement had no sigma antigen. The leukemic cells arising at the site of thymus grafts were derived from the graft itself (C3Hf) or from the host (C3Hf times CBA/H-T6T6)F1 cells, most probably bone marrow cells which are repopulating into the graft. When the mice were treated with BNU after the lymphoid elements in the grafted thymus had been replaced by host cells, leukemia mainly composed of host-origin cells developed. Leukemia in which neoplastic cells in the thymus grafts were of donor origin and those in other hematopoietic tissues were of host origin was found not infrequently. The present results mean that the target cells in BNU leukemogenesis are distributed within and outside the thymus and that some leukemias are of multifocal tissue origin.
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Explore the source record for details and available documents.
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