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Jyoji Yamate

Publications and source records attributed to Jyoji Yamate.

28 records · Page 2Linked to original sources

Angioarchitecture of tumors induced by two different cloned cell lines established from a transplantable rat malignant fibrous histiocytoma.

Angiogenesis, a biologic process whereby endothelial cells divide and migrate to form new blood vessels, is a key step in tumor growth, invasion, and metastasis. In the present study, we investigated the differences in angioarchitecture between two different tumors induced by cloned cell lines (MT-8 and MT-9), derived from a transplantable rat malignant fibrous histiocytoma, by scanning electron microscopy of vascular corrosion casts. During a 3-week observation period after implantation, the growth of MT-8 tumors appeared to be faster than that of MT-9 tumors. Histologically, MT-8 tumors were of the uniformly undifferentiated sarcoma type arranged in characteristic organoid structures, and MT-9 tumors showed a storiform growth pattern. In MT-8 tumors, neovascularization occurred by sprouting at postimplantation (PI) week 1, and the newly formed capillaries gradually became more tortuous. In MT-9 tumors, at PI week 1, the corrosion casts of newly formed capillaries mainly showed a wavy course but no finger-like outgrowths of capillaries were seen. At PI weeks 2 and 3, the sprouting was seen specifically in MT-9 tumors, forming basket-like structures and glomeruloid structures of capillaries. These results indicate that angiogenesis or angioarchitecture of MT-8 tumors is different from that of MT-9 tumors, depending on the differences in their tumor histology and by the features like absence or presence of basket-like structures and glomeruloid structures of capillaries.

Animals↗

Relationship of interstitial edema with L-cysteine-induced sperm granulomas in the pubertal rat epididymis.

Although the pathogenesis of sperm granulomas is complicated, the leakage of spermatozoa into extraluminal tissues is regarded as a crucial event. It has been previously shown that pubertal rats injected with L-cysteine develop interstitial edema followed by sperm granulomas in the epididymis. In this study we investigated the relationships between these two lesions in 6-week old rats given daily intraperitoneal injections of L-cysteine (1,000 mg/kg body weight) for 4 weeks. Rats were examined during weeks 0, 1, 2, 3 and 4 after the first injection. Interstitial edema (moderate or severe) and sperm granulomas were seen in the corpus and cauda epididymis of L-cysteine-treated rats in study weeks 2, 3, and 4. There was no marked alteration of basement membrane of the epididymal ducts in the edematous tissues as shown by immunohistochemistry with an antilaminin antibody. However, the extravasation of Evans blue dye given I hour before necropsy suggested that the severe interstitial edema was due to increased vascular permeability. In addition, a small number of neutrophils were seen in the edematous tissues, suggesting that they might play a role in the increased vascular permeability and leakage of epididymal fluid. Interestingly, slight interstitial edema was observed in the caput epididymis in both control and L-cysteine-treated rats in early study weeks 0, 1, and 2. It is speculated that this change was related to the leakage of epididymal fluid due to increased intraluminal pressure depending on rat epididymal maturation. Taken together, these findings suggest that the severe interstitial edema results from increased vascular permeability. This, along with increased intraluminal pressure, might be the trigger for duct rupture, the prerequisite for sperm granuloma formation associated with excessive doses of L-cysteine.

Animals↗

Preferential induction of mammary tumors in p53 hemizygous BALB/c mice by fractionated irradiation of a sub-lethal dose of X-rays.

BALB/c mice are susceptible to radiation-induced mammary tumors as well as lymphomas. We investigated the effects of the p53 deficient allele and of X-irradiation on the tumor spectrum in the BALB/c background. Substantially all p53 -/-animals died of thymic lymphomas before 36 weeks of age, while none of the p53 +/+ animals died during that period. At this age, mortalities of p53 +/- females and males were 5% (1/22) and 11% (1/9), respectively, due to non-thymic lymphoma and sarcoma. When exposed to 4 Gy of X-irradiation, 100% (44/44) and 95% (18/19) of p53 +/- mice died with tumors within 36 weeks. Among these, the predominant cause of death was lymphoma in either sex [26/44 (59%) in females; 13/19 (68%) in males]; mammary adenocarcinoma (15/44, 34%) and sarcoma (3/19, 16%) were semi-dominant in females and males, respectively. The mortalities of similarly treated p53 +/+ mice were 16% (5/31) in females and 17% (3/18) in males: virtually all deaths were due to thymic lymphomas in either sex. When exposed to 4 currency 0.7 Gy of X-irradiation at weekly intervals, 23/23 (100%) of the p53 +/-females died of tumors within 36 weeks. In these animals, mammary adenocarcinoma (15/23, 65%), instead of lymphoma (7/23, 30%), was dominant. None of the similarly treated p53 +/+ females developed malignant tumors during the period. Mammary adenocarcinomas generated in p53 +/- females exposed or non-exposed to radiation showed a frequent loss of the p53 wild-type allele. Hence, we provided a useful experimental system to study radiation-induced mammary tumors in mice.

Adenocarcinoma↗

Immunophenotypical changes of neoplastic cells and tumor-associated macrophages in a rat dendritic cell sarcoma-derived transplantable tumor line (KB-D8).

Basically, dendritic cell-derived sarcomas are characterized by expression of major histocompatibility complex class-II molecules, but the biological properties of the tumor cells remain to be elucidated. Recently, we established a novel transplantable cell line (KB-D8) from a dendritic cell sarcoma found in an F344 rat. In the present study, we investigated immunophenotypical changes of KB-D8 tumor cells and tumor-associated macrophages (TAMs) appearing in relation to tumor development in syngeneic F344 rats. A number of neoplastic cells in 0.5-cm-diameter KB-D8 tumors showed immunoreactions to OX6 (specific for rat antigen-presenting cells), ED1 (for rat exudate macrophages), and ED2 (for rat resident macrophages), and 72% and 11% of the OX6+ cells were double-immunostained with ED1 and ED2, respectively. Interestingly, the immunoreactions to these antibodies were gradually reduced with increasing size of KB-D8 tumors of 1-, 2-, and 3-cm diameter. These findings indicated that immunophenotypes of dendritic cell-derived sarcomas may be changeable depending on microenvironmental conditions in vivo. Many TAMs seen outside KB-D8 tumors reacted to OX6, ED1, and ED2; the numbers of TAMs immunopositive for these antibodies also decreased as the tumor grew. Similarly, the earlier temporary increase and subsequent gradual decrease in ED2+ and OX6+ cell numbers were observed in the spleen and liver of KB-D8-bearing rats. The reverse-transcription polymerase chain reaction showed mRNA expressions of granulocyte/macrophage-colony stimulating factor, monocyte-chemoattractant protein-1, and osteopontin in KB-D8 tumor tissues. Although the functional roles (biphasic roles: suppressing or promoting) of these factors should be investigated further in relation to tumor development, the factors might be partially responsible for the TAM reactions. KB-D8 would be a useful experimental model to investigate the biological characteristics of dendritic cell sarcomas and tumor immunology in the host.

Animals↗

Protective effect of taurine against renal interstitial fibrosis of rats induced by cisplatin.

This study was undertaken to investigate the effect of taurine on the infiltration of macrophages and the progression of renal interstitial fibrosis in the kidneys of rats treated with cisplatin (CDDP). Male rats in different groups were treated as follows: (1) saline as control, (2) CDDP and (3) CDDP plus taurine in drinking water. At weeks 2, 4 and 6 after the fifth CDDP injection, we examined platinum content, the kinetics of macrophages and the areas of fibrosis. In the histologic analyses, fibrotic areas were found to have developed around dilated or atrophic tubules in the corticomedullary junction in the kidneys of CDDP-treated rats, while CDDP-plus-taurine-treated rats showed a reduction of the extent and magnitude of damage. These findings reflect the fact that the percentage of fibrotic areas in the kidney of CDDP-plus-taurine-treated rats was significantly lower than in that of CDDP-injected rats throughout the recovery period ( P<0.05). Compared with normal rats, the macrophages in CDDP-injected rats showed significant increases in number at weeks 2, 4 and 6 ( P<0.05). In contrast, the number of macrophages in CDDP-plus-taurine-treated rats was significantly smaller than that of CDDP-injected rats. These results suggested that taurine suppressed the increase of infiltrating macrophages, and led to the attenuation of renal interstitial fibrosis ( P<0.05).

Animals↗

Establishment and characterization of transplantable tumor line (KB) and cell lines (KB-P and KB-D8) from a rat thymus-derived dendritic cell sarcoma.

A transplantable tumor line (KB) was established in syngeneic rats from a naturally occurring sarcoma that had arisen in the thymus of a 24-month-old male F344 rat. Further, a cell line (KB-P) was induced from KB and a cloned cell line (KB-D8) was isolated from KB-P. The primary thymic tumor and KB tumors showed heterogeneous histological growth patterns such as sheet-like, ill-defined bundle, fascicular and interwoven fashions, consisting of spindle cells, oval cells and histiocytic large round cells. Immunohistochemically, neoplastic cells in KB tumors and KB-P and KB-D8 cultures reacted to vimentin and were labeled with antibodies of OX6 (for rat major histocompatibility complex class-II antigens), ED5 (for rat follicular dendritic cells; FDCs) and RED-1 (for interdigitating dendritic cells) in varying degrees, indicating that neoplastic cells exhibited the immunophenotypes of rat dendritic cells. In addition, neoplastic cells were immunoreactive to ED1 (for rat monocytes/macrophages) and ED2 (for rat tissue macrophages), and also showed positive reactions to histiocytic lysosomal enzymes such as acid phosphatase and non-specific esterase. Ultrastructurally, neoplastic cells had cell surface projections, cisterna-like structures and variously developed lysosomes in the cytoplasm. Based on these findings, the present tumor was regarded as dendritic cell-derived sarcoma capable of expressing macrophage-like and histiocytic nature. A reverse-transcription polymerase chain reaction method revealed that the addition of lipopolysaccharide dose dependently increased the expression of mRNA of transforming growth factor-beta1, a proinflammatory factor, in KB-D8 cells. The transplantable line (KB) and cell lines (KB-P and KB-D8) may become useful tools for studying the histogenesis and pathobiological functions of dendritic cells.

Animals↗

Establishment of a transplantable tumor line (IP) derived from rat pulmonary carcinoma, developing humoral hypercalcemia of malignancy in IP-bearing rats.

A transplantable tumor line (IP) was established in syngeneic rats from a spontaneous pulmonary carcinoma found in a male F344 rat aged 25 months. A tissue fragment of IP grew into a nodule, 2-3 cm in diameter, 2-3 weeks after implant, and IP has been serially passed through 26 generations. Lined by cuboidal or columnar epithelial cells, the primary tumor consisted of completely alveolar architecture. However, IP tumors developed various growth patterns such as glandular, acinar, trabecular, cord, and solid, and consisting of epithelial cells showing cellular atypia. Ultrastructurally, neoplastic cells had microvilli, basement membranes, and desmosomes, and occasional cells possessed dense cytoplasmic granules. Interestingly, it was shown by the immunohistochemistry, the RT-PCR method, and immunoradiometric assay that IP tumor cells produce parathyroid hormone-related protein (PTHrP). During a 3-week observation period after implant, IP-bearing rats showed severe emaciation, hypercalcemia, and hypophosphatemia, as well as an increase in osteoclastic areas and a decrease in shaft thickness of the femurs. These were considered to be due to a marked elevation of plasma PTHrP levels. Furthermore, IP-bearing rats developed calcification in various organs including the kidneys, lungs, and heart. These findings in IP-bearing rats were similar to those of humoral hypercalcemia of malignancy (HHM) reported in human cancer patients. PTHrP plays a central role in the development of HHM, but the mechanisms of HHM remain poorly understood. IP may become a useful model for studying the pathogenesis of HHM and the pathophysiological role of PTHrP.

Actins↗

The myelin vacuolation (mv) rat with a null mutation in the attractin gene.

We recently found a spontaneous tremor mutant in an outbred colony of Sprague-Dawley rats. The tremor behavior was exhibited from around 3 weeks of age and inherited as an autosomal recessive trait. The mutant rats had variously sized vacuoles in the neuropil and white matter throughout the central nervous system, especially in the brain stem, cerebellum, and spinal cord. Ultrastructurally these vacuoles mainly consisted of splitting of myelin lamella both in the periaxonal and intermyelinic spaces. Linkage analysis using intercross progeny between the myelin vacuolation (mv) rat, named after the pathologic characteristics, and normal control rat strains showed that the mv phenotypes were cosegregated with polymorphic markers adjacent to the Atrn (Attractin, formerly zi [zitter]) locus on rat chromosome 3. A test for allelism suggested that the mv mutation was a new allele in ATRN: In comparison with a marked decrease of Atrn(zi)/Arn(zi), Northern blot analysis revealed no expression of Atrn mRNA in the brain of the mv rats. Finally, a genomic deletion including exon 1 of the mv rats was detected by genomic and sequence analyses. Discovery of the rat null mutation Atrn(mv), different from Atrn(zi), provides a new animal model for studying the functions of the attractin protein.

Animals↗

Development of sperm granulomas in the epididymides of L-cysteine-treated rats.

We investigated the histopathological effects of excess L-cysteine on the male rat reproductive tract during sexual maturation. Male 6-week-old Sprague-Dawley rats were injected intraperitoneally daily with L-cysteine, 1,000 mg/kg body weight, for 1, 2, 3, and 4 weeks. L-Cysteine-treated rats developed sperm granulomas in the epididymides at an incidence of 0% (0/6), 50% (3/6), 83% (5/6), and 100% (6/6) in rats examined at study weeks 1, 2, 3, and 4, respectively. These sperm granulomas were unilateral or bilateral, and most frequently involved the proximal cauda region of the epididymides. Interestingly, small ducts, indicative of immaturity, were seen frequently in L-cysteine-treated rats. These findings suggest that the maturation of epididymides in L-cysteine-treated rats might be delayed. Additionally, dilated ducts and interstitial edema, suggestive of an increase in intraluminal pressure, were seen often in the epididymides of L-cysteine-treated rats. Labeling spermatozoa and epithelial cells with monobromobimane indicated no influence of the thiol-disulfide status of L-cysteine to the epididymides. The testes and prostate glands also showed no effects, suggesting that inhibited epididymis maturation was not a result of hormonal deficiencies. We speculate that defective development of the ducts might result in aberrant fluid flow, leading to ductal rupture in the epididymides. In that case, sperm granulomas might form around leaked spermatozoa.

Animals↗

Establishment of a transplantable rat pulmonary carcinoma-derived cell line (IP-B12) as a new model of humoral hypercalcemia of malignancy and bone metastasis.

A cloned cell line (IP-B12) derived from a transplantable rat pulmonary carcinoma (IP), of which neoplastic cells produce parathyroid hormone-related protein (PTHrP), was established. Tumors induced in syngeneic F344 rats by intraperitoneal injection of IP-B12 cells had features of pulmonary adenocarcinomas, consisting of neoplastic cells immunopositive to PTHrP. The IP-B12 tumor-bearing rats developed severe emaciation and hypercalcemia, with a marked elevation of plasma PTHrP level; there was an increase in osteoclastic areas of the femur and calcium depositions in systemic organs, indicating progression to humoral hypercalcemia of malignancy (HHM) in the tumor-bearing rats. In addition, the injection of IP-B12 cells into the left cardiac ventricle of syngeneic rats resulted in osteolytic skeletal metastases in the long bones and vertebrae. In the metastatic lesions, histologically, neoplastic cells showed an immunopositive reaction to PTHrP, and a prominent osteoclastic activity was seen; bone lesions, including osteolysis, fracture, and nerve compression as well as replacement of bone marrow cells by proliferated tumor cells were similar to those reported in human cancer patients with bone metastases. IP-B12 is a new animal model for HHM and osteolytic bone metastases, and will become a useful tool for studies on the pathogenesis and therapeutic strategies for such conditions.

Animals↗