Phytotoxins from the Septoria spp. plant pathogenic fungus on leafy spurge.
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Biomedical subjects
Publications and source records attributed to S Yoshida.
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The tumor of the thoracic cavity, which arose from the ribs, was diagnosed as mesenchymal chondrosarcoma. No distant metastasis was observed. Histologically, the tumor was characterized by the nests of well-defined cartilaginous tissue within a proliferation of primitive mesenchymal cells. Additionally, the deformed blood vessels compressed by the proliferating mesenchymal cells exhibited clear stag-horn appearance. Immunohistochemically, most neoplastic cells that formed multifocal cartilaginous islands were positive for S-100 protein, while the surrounding mesenchymal cells were negative. This is the first report of canine mesenchymal chondrosarcoma of the ribs.
We reviewed retrospectively the MRI examinations of 108 knees of 80 children to identify the prevalence of a high signal in the menisci of those without symptoms. There were 51 boys and 29 girls with a mean age of 12.2 years (8 to 15). The prevalence of a high signal within the menisci was 66%, significantly higher than that in an adult group (29%). The prevalence decreased with age: grade-2 and grade-3 changes were observed in 80% of menisci at ten years of age, in 65% at 13 years and in 35% at 15 years. The prevalence of high signals also decreased with increased skeletal maturity at the knee. We emphasise the importance of awareness of the high prevalence of a high signal intensity in the menisci of children, especially in early adolescence.
Total-body irradiation (TBI) is an accepted modality to treat patients with disseminated tumors. The influence of the treatment on normal tissues is evaluated using mice by measuring the rate of the induction and distribution of apoptosis, as well as DNA fragmentation which occurs in the murine liver within hours of irradiation. Unanesthetized female C3H/He mice were exposed to gamma-ray TBI of 2, 7, and 20 gray (Gy) delivered from 60Co at a dose rate of 114 cGy/min. Frozen sections of livers which were excised from the animals at various times after irradiation were stained by hematoxylin-eosin (H-E) to count numbers of apoptotic cells, or were examined to detect DNA fragmentation. The percentages of apoptotic cells and length of the period during which the maximum levels of the percentages were exhibited showed a dose-dependent increase in the sections stained with H-E. No positive cells for 3'-OH ends of fragmented DNA were found in the liver before TBI, whereas positive cells were observed immediately after irradiation without dose-dependency, these positive cells returned to nearly basal levels after several hours. Positive cells were observed prior to showing apoptosis, suggesting that DNA fragmentation occurs immediately after TBI independent of apoptosis. The difference in the time courses between induction of DNA fragmentation and of apoptosis was not observed in other organs or in the samples treated with the detergent. These results suggested that the 3'-OH ends newly generated by TBI were masked by a detergent-soluble DNA-binding molecule which might be preferentially present in the murine liver.
OBJECTIVE: This study investigated the relationship between maxillary dental arch form and distribution of postsurgical scar tissue on previously denuded bone in isolated cleft palate patients. METHOD: The palatal blood flow of 21 Japanese isolated cleft palate patients (6 males, 15 females) was examined by laser doppler flowmetry to determine the scar tissue areas. All had undergone pushback operations for palatal repair at around 18 months of age. Tissue blood flow was examined at a time ranging from 11 years, 5 months to 19 years, 9 months of age. To evaluate the maxillary dental arch form, dental casts obtained at the start of orthodontic treatment (a mean age of 8 years, 4 months) were analyzed. RESULTS/CONCLUSIONS: Scar tissue distribution in the 21 cases was classified into five types. Characteristic features in the maxillary dental arch form were found in each of the five types according to the extent of the scar tissue. It was evident that the severity of the maxillary dental arch constriction was closely related to the scar tissue distribution on palates.
A 66-year-old man was admitted with destructive arthropathy, and calcium pyrophosphate dihydrate was demonstrated in the synovial fluid specimen. He was found to have a hyponatremia. The serum sodium concentration was 121 mmol/l, plasma arginine vasopressin (AVP) 6.6 pmol/l, and serum interleukin (IL)-6 96 pg/l. The clinical findings suggest the diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). However, destructive arthropathy with increased values of C-reactive protein and IL-6 is the only background of SIADH in this patient. We suggest the possibility that IL-6 produced at inflammatory lesions may have stimulated an excessive release of AVP resulting in the hyponatremia and hypochloremia of SIADH.
Brain metastasis in patients with disseminated nonseminomatous germ cell tumor (NSGCT) has been considered to occur rarely. The authors present the case of a 43-year-old man with an enlarged left testicle, a palpable inguinal tumor, multiple lung tumors, and a large cerebellar tumor. In separate operations, performed 1 month apart, the large cerebellar tumor and the testicular tumor were excised. Elements of teratocarcinoma, embryonal carcinoma, and choriocarcinoma were present in both the brain and testicular tumors. After chemotherapy in which bleomycin, etoposide, and cisplatin were used, the lung tumors and also the surrounding metastasis disappeared; the patient now leads a useful life and remains free from cancer in all organs. The authors suggest that surgical removal of tumor before initiating radiotherapy and chemotherapy for large brain metastasis from NSGCT will produce better results than using the nonsurgical treatments alone.
Bredinin is an immunosuppressive drug which is used clinically in Japan. In this study, we investigated bredinin's molecular mode of action to clarify its immunosuppressive effects. We focused on the DNA polymerases in the somatic DNA synthesis which may be required in the process of lymphocyte differentiation. We found that bredinin-5'-monophosphate (breMP) could be a potent inhibitor of mammalian DNA polymerase alpha(pol.alpha) and (pol.beta) in vitro, although bredinin itself has no such effects. BreMP inhibited the pol. alpha activity at less than 7 micrograms/ml and the pol. activity at 7 micrograms/ml. Neither breMP nor bredinin influenced the activities of a plant DNA polymerase, prokaryotic DNA polymerases such as E. coli DNA polymerase I and Taq DNA polymerase, or DNA-metabolic enzymes such as DNase I, indicating that breMP selectively suppressed the activities of the mammalian DNA polymerases. For pol., beta breMP acted by competing with both the substrate and template-primer. For pol. alpha, it acted by competing only with the substrate, and non-competitively with the template-primer. The ribose of bredinin is quickly and quantitatively converted to its ribose-5'-phosphate form in vivo as soon as it is incorporated into cells. The action mode of bredinin and its use as an immunosuppressive drug are discussed based on these results.
Telomerase activity has been evaluated for many kinds of malignancies, and it has been clarified that the activity reflected the malignant potential of the tumor. With regard to radiation therapy for cancer, simple and reliable assays for the prediction of therapeutic effect have not been fully developed yet. Therefore, we aimed to determine whether telomerase activity is changed by radiotherapy for advanced head and neck malignancies, and to clarify the possible correlation of telomerase activity with the therapeutic effect of radiation therapy and patients' clinical outcomes. Twenty-five patients with advanced cancers of the oral cavity and oropharynx were examined. All the cancers were confirmed histopathologically as squamous cell carcinomas. Biopsies were performed before treatment and at doses of 4 and/or 10 Gy, and 20 Gy of radiotherapy. To semi-quantitate telomerase activity, a highly sensitive PCR-based telomeric repeat amplification protocol assay was performed. Nineteen of the 21 cancers (90.1%) showed telomerase activity of varied extents prior to radiation therapy. Nine of the 25 patients showed continuous elevations of telomerase activity (> 10 TPG units/microg protein) in their tumors during radiation therapy, and these nine showed 13.8-216.9 TPG units/microg protein at 20 Gy of radiotherapy. In eight of the nine patients, tumors did not respond well to radiotherapy and relapsed locally in a short period after the treatment. On the other hand, in another group of 11 patients, who showed low (< 10) and/or no activity of telomerase in their tumors at 20 Gy of radiotherapy, there were nine patients whose tumors responded well to radiotherapy (p < 0.025 by the chi2 test). None of them relapsed locally in the follow-up period of approximately 21 months, and the difference was statistically significant (p < 0.025 by the chi2 test). It is concluded that the high activity of telomerase in tumor tissue at 20 Gy of radiotherapy can predict a poor therapeutic effect of radiation therapy and unfavorable patients' outcomes for advanced cancers of oral cavity and oropharynx.
The mechanism by which radiation induces human peripheral T cell apoptosis is not known. We examined sequential changes in post-irradiated peripheral blood mononuclear cells (PBMC(S)) taken from normal volunteers, by using flow-cytometer and an anti-CD3 monoclonal antibody, annexin V, propidium iodide, anti-Fas antibody, and anti-Fas ligand antibody. After 5 or 10 Gy of irradiation with a 60Co radiation therapy unit, most of the human peripheral T cells showed positivity against annexin V in 15 h, and positivity against propidium iodide in 23 h after irradiation. On a microscopy-video system, approximately 80% of mononuclear cells revealed apoptotic changes in 24 h after irradiation. Because of its proposed role in activation-induced cytotoxicity, we also examined the Fas (CD95/Apo-1) pathway in killing T cells by irradiation. Irradiated PBMC, displayed no increase in surface Fas expression and caspase-3 activity relative to non-irradiated cells. In addition, the anti-Fas ligand failed to eliminate the apoptotic death of PBMC, after irradiation. These results suggest that irradiation induces direct apoptosis of T cells by a Fas-independent mechanism.
Fas antigen, also termed APO-1 or CD95, is a transmembrane protein and a member of the tumor necrosis factor receptor/nerve growth factor receptor superfamily which mediates apoptosis upon oligomerization. The Fas/Fas ligand system is considered to be a key regulator of apoptosis. Recently, we have demonstrated that Fas antigen expression is induced by low-dose irradiation of some types of lymphomas, and we also demonstrated that irradiation-induced Fas antigen expression increased with the passage of time until peaking at 48 h after irradiation in CML-C1, CML-C2, DL-40, and DL-95 cell lines. In this study, we also examined the potential cytotoxicity of Fas ligand peptide against several types of lymphoma/leukemia cell lines that showed induction of Fas antigen expression under irradiation. Flow cytometry analysis was performed at 6, 24 and 48 h after irradiation. Samples (1 x10(6) cells/ml) from irradiated and non-irradiated cells of each cell line were incubated with or without 5 microg/ml of Fas ligand peptide for 2 h at 37 degrees C in a humidified atmosphere of 5% carbon dioxide (CO2) in air. The killing effect of Fas ligand against cell lines of CML-C1, DL-40, and DL-95 were clearly identified as the percentage of cells with Fas antigen expression induced by irradiation. Concerning HD-70 cell line, for which soluble Fas antigen has been identified, the killing effects were clearly observed in samples pre-treated with PBS washings. To our knowledge, this is the first report describing a possible application of the Fas/Fas ligand system in treatment of certain types of malignancies in which Fas antigen is inducible by irradiation.
The effect of high-dose irradiation on telomerase activity was examined in some human lymphoma (DL40, DL95, DL110) and myeloma (U266) cell lines. The survival rate was reduced in DL40, DL110 and U266 by irradiation. Irradiation, however, showed no effect on the rate of DL95. Telomerase activity was detected in non-irradiated samples of all cell lines, as measured by PCR-based telomeric repeat amplification protocol assay. The telomerase activity increased 2-6.5 fold by irradiation. Especially in DL110, the activation increased in a dose-dependent manner. In the early phase after irradiation, we observed no correlation between telomerase activity and cell viability, suggesting that telomerase-mediated chromosome healing might not be a major cause and/or not sufficiently effective to protect the cells from irradiation.
The anti-tumor effect and its mechanism of the herbal medicine sho-saiko-to were investigated on a murine malignant melanoma cell line (Mel-ret). Sho-saiko-to induced apoptotic cell death of Mel-ret cells with a definite increase of cell surface Fas antigen and Fas ligand (FasL). Sho-saiko-to arrested Mel-ret cells in G1 phase by decreasing the expression of cyclin-dependent kinase (cdk) 4 and its homologue cdk6. Kinase activities of cdk4 and cdk6 were identified to be downregulated by sho-saiko-to. Ingredient analysis revealed that baicalin is likely the main active constituent in the upregulation of Fas antigen and Fas ligand, while glycyrrhizin is the main constituent in the inhibition of cdks.
The abilities of 9 kinds of human biliary tract carcinoma cell lines to invade through basement membrane or type I collagen were examined using an in vitro invasion assay system. The correlations between invasiveness and morphologic characteristics of the carcinoma cells in 3 dimensional collagen gel were also examined. most of the biliary tract carcinoma cell lines kept the abilities of glandular differentiation and basement membrane formation of the original tumor. Their invasiveness, however, correlated with the degree of in vitro morphologic differentiation regardless of their original morphology.
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Our indications of endoscopic mucosal resection (EMR) for early gastric cancer (EGC) as a radical treatment are as follows: 1) histology: intestinal type; 2) macroscopic type: IIa and IIc; 3) without ulcerative change. We do not put restrictions on the size of the lesion. EMR is performed on lesions which are suspected to have submucosal invasion for a diagnostic purpose. The ratio of EMR cases to the total EGC cases is increasing in recent years and amounted to about 40% of EGCs treated at the National Cancer Center Hospital in '96. From '87-'96, we had 440 cases of EGCs (intestinal type, histologically) at the National Cancer Center Hospital and National Cancer Center Hospital East. Eighty-five cases (19.3%) turned out to have submucosal invasion and judged non-curative resection. The overall rate of cut-end-free cases was 72.3%, while the overall rate of curative resection (excluding cases with submucosal invasion) was 63.0%. Though we had 37 cases of recurrence after EMR, there were no cases of death from the original disease with additional treatment or observation (due to complication or age). The cut-end-free rates of each period ('87-'90, '91-'93, '94-'96) were 53.1%, 61.3% and 81.6%, respectively. The mean diameter of the lesion of each period became larger, at 11.9 mm, 12.0 mm and 14.0 mm, respectively. To resect a larger lesion in one piece, we began EMR with cutting the mucosa around the lesion using a newly improved endoscopic device called an insulation-tipped diathermic knife (IT knife) from '95. With this IT knife, we could resect 75% of the lesions sized 11-20 mm in one piece, while we could resect 29% with the conventional method (strip biopsy). Though the results of EMR are improving in recent years, new endoscopic technics of EMR to resect easily and surely are expected.
PURPOSE: Glutamate immunoreactivity in the mammalian retina has generally been observed using immersion fixation. The authors investigated glutamate immunoreactivity in the detached cat retina and reevaluated this activity in the normal retina using rapid fixation by perfusion. METHODS: Unilateral retinal detachment was produced in cats by injecting 0.25% sodium hyaluronate into the subretinal space using a glass micropipet. The eyes were fixed by perfusion with a mixture of 1% glutaraldehyde and 4% formaldehyde 10 minutes and 60 minutes after detachment, and then they were examined by conventional light and electron microscopic immunocytochemistry. RESULTS: In contrast to previous reports based on immersion fixation, the inner segment was not glutamate immunopositive in the normal retina. The inner segment showed intense glutamate immunoreactivity 10 minutes and 60 minutes after retinal detachment. CONCLUSIONS: Glutamate immunoreactivity in photoreceptor inner segments may be a postmortem change induced by strong ischemia. Perfusion fixation is of critical importance when studying the immunocytochemical distribution of glutamate in the retina.
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