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Biomedical subjects

T Inomata

Publications and source records attributed to T Inomata.

At least 37 records · Page 2Linked to original sources
PubMed1999

Obstructive uropathy and hydronephrosis in male KK-Ay mice: a report of cases.

Uropathy associated with hydronephrosis was observed frequently in our male KK-Ay mouse colony during a long-term study of diabetes. The lesion occurred in 24 of the 31 KK-Ay male mice and accounted for the greatest number of spontaneous deaths among them. It was observed after 4 months of age and involved about hard plugs of altered seminal material resembling the seminal vesicle secretion. The plugs became impacted in the urethral bulb and the bladder. The penile anatomy, with its flexure, pressure on the urethra from the bulbocavernosus muscle, and the characteristic ability of the seminal fluid to easily coagulate to form the vaginal plug may have contributed to the lesion. Correlation between development of the uropathy and diabetes has not been established.

Animals↗
PubMed1999

Underdevelopment of fetal thyroid follicular cells in athymic nude mouse (BALB/cAnNCrj-nu/nu) observed by electron microscopic morphometry.

Fetal thyroid follicular cells of congenitally athymic nude mouse (BALB/cAnNCrj-nu/nu) were studied with an electron microscope. The area of the entire cell, nucleus and mitochondrion were measured and compared in athymic and euthymic fetal nude mice (BALB/cAnNCrj-nu/+) at 18 days of gestation. The mean area of cytoplasm was significantly smaller in homozygous athymic nude mice than in heterozygous euthymic ones. The mean area of the mitochondrion was also smaller in homozygous athymic nude mice, but the difference was not statistically significant. There was no significant difference between the two groups in the area of the nucleus. These findings suggest that the thyroid gland of athymic nude mice is still underdeveloped at the end of gestation as compared to that of their euthymic littermates.

Animals↗
PubMed1999

An augmentation of Fas (CD95/APO-1) antigen induced by radiation: flow cytometry analysis of lymphoma and leukemia cell lines.

An augmentation of Fas antigen induced by radiation was examined using flow cytometry. Six cell lines established from lymphomas or leukemias (HD-70, FLAM-76, CML-C-1, CML-C-2, DL-40 and DL-95) were used in this study. Each cell line was distributed to two dishes. The cells in one dish were irradiated at 10 Gy with cobalt-60 gamma rays. The control cells were not irradiated. At 6 h, 24 h, and 48 h after treatment, irradiated and non-irradiated cells of each cell line were stained with fluorescein isocyanate (FITC)-conjugated anti-human Fas antibody, and analyzed with flow cytometry. Mean fluorescence intensity (MFI) values of irradiated or non-irradiated cells were examined. MFI rates (MFI value of irradiated cells/MFI value of non-irradiated cells) of each cell line were calculated at each investigated time point, and an augmentation of the Fas antigen expression with radiation was evaluated. FLAM-76 did not express Fas antigen at any time. An augmented expression of Fas antigen due to irradiation was observed in the other five cell lines. These findings strongly suggest that radiation can augment Fas antigen expression in certain tumor cells. Further studies using Fas ligand or specific anti-Fas antibody are needed.

Antibodies↗
PubMed1999

Lung metastasis suppression of the bifunctional new radiosensitizer KIN-806.

KIN-806 is one of the newly developed 2-nitroimidazole derivative hypoxic cell radiosensitizers. The tumor growth control and the suppression of lung metastasis induced by KIN-806 were evaluated. Female C3H/He mice and SCCVII tumor cells were used. 30 Gy or 40 Gy was delivered as local irradiation. 0.2 g/kg or 0.4 g/kg KIN-806 was administered 30 min before this treatment to the KIN-806 administered groups. The enhancement ratio of KIN-806 evaluated using the growth delay method was 1.8. KIN-806 showed an excellent effect as a radiosensitizer. Furthermore, KIN-806 suppressed lung metastasis regardless of radiation, and the control of the metastatic lung nodules did not depend on the irradiation dose but rather on the KIN-806 dose (0.2 g/kg < 0.4 g/kg). KIN-806 is a promising bifunctional radiosensitizer which promotes anti-tumor activity in addition to having a radiosensitizing effect.

Animals↗
PubMed1998

TX-1877: design, synthesis, and biological activities as a BRM-functional hypoxic cell radiosensitizer.

PURPOSE: 2-Nitroimidazole acetamide TX-1877 and its derivatives (TX-1877 analogs) were designed, synthesized, and evaluated by their in vitro and in vivo radiosensitization, tumor growth control, suppression of lung metastasis, and immunopotentiation, as biological response modifier (BRM)-functional hypoxic cell radiosensitizers. MATERIALS AND METHODS: TX-1877 analogs were designed and synthesized in our laboratory. In vitro radiosensitizing ability was estimated using EMT6/KU cells under hypoxic conditions. In vivo radiosensitization, antimetastasis, and immunopotentiation were evaluated using female C3H/He mice bearing the SCCVII tumor. Days (15 or 10) after the inoculation of 10(5) SCCVII tumor cells into the hinder thigh, a drug (0.4 mg/g) was administered i.p. and local irradiation of 30 Gy was given at 30 min after its administration. Tumor growth was observed for 20 days and mice were euthanized to count the number of metastatic nodules on the surface of the lungs. Tumor tissues were extirpated and stained by the ABC method at 1, 2, and 3 weeks after treatment for immunological evaluation. RESULTS: Novel types of bifunctional radiosensitizers, TX-1877 and its analogs possessing BRM-functions (i.e., antimetastatic and immunopotentiation effects) were developed. In vitro radiosensitizing abilities of TX-1877 and its analogs, with their partition coefficient values of more than 0.050, were comparable to misonidazole (MISO) at their doses of 1 mM. Tumor regrowth was suppressed evidently 20 days after the treatment in the irradiated group with TX-1877 (TX-1877 plus R) and with KIN-806 (KIN-806 plus R). The former group reduced markedly the mean number of metastatic lung nodules regardless of radiation therapy. TX-1877 and KIN-806 plus R induced helper T lymphocytes. The TX-1877, TX-1877 plus R, KIN-806, and KIN-806 plus R enhanced macrophage infiltration for 3 weeks after treatment. CONCLUSION: TX-1877 is an excellent BRM-functional hypoxic cell radiosensitizer, expected to be useful for clinical use.

Animals↗
PubMed1998

T cells with similar T-cell receptor beta-chain complementarity-determining region 3 motifs infiltrate inflammatory lesions of synthetic peptides inducing rat autoimmune myocarditis.

Experimental autoimmune myocarditis (EAM) resembles the giant cell myocarditis seen in humans, and recurrent forms lead to dilated cardiomyopathy. EAM has been shown to be a T cell-mediated autoimmune myocarditis. We have previously shown that cDNA encoding Vbeta complementarity-determining region (CDR) 3 from heart- and pericardial space-infiltrating T cells in EAM induced by rod cardiac myosin contains more restricted sequences than that from normal spleen T cells. Recently, it has become apparent that several epitopes of EAM exist in rod cardiac myosin; therefore, T cells infiltrating into lesions may recognize certain epitopes in EAM induced by rod cardiac myosin. In this study, we examined heart- and pericardial space-infiltrating T-cell clonotypes in EAM induced by synthetic peptides of cardiac myosin. EAM was produced by immunization with synthetic peptides corresponding to N-terminally acetylated amino acids 1539 to 1555 of rat cardiac myosin alpha heavy chain. Five of 12 rats receiving synthetic peptides developed macroscopic signs of myocarditis. To examine T-cell receptor (TCR) Vbeta expression and CDR3 of the TCR beta chain of lesion-infiltrating T cells in EAM, total RNA was isolated from heart, pericardial effusion, spleen, lymph node, and peripheral blood. TCR Vbeta expression of the T cells infiltrating the lesions revealed a predominance of Vbeta4. On the basis of single-strand conformation polymorphism analysis for CDR3 of the TCR Vbeta4 chain, heart- and pericardial space-infiltrating T cells were considered to be oligoclonal, whereas spleen, lymph node, and peripheral blood in a rat with EAM and spleen in a native rat were considered to be polyclonal. In the same rat, clonotypes of heart-infiltrating T cells were almost the same as those of pericardial space-infiltrating T cells. Furthermore, on sequence analysis for CDR3 of the TCR Vbeta4 chain, the amino acid motifs were similar among T cells infiltrating into lesions of different EAM rats. In the present study, TCR beta chains of heart- and pericardial space-infiltrating T cells in EAM induced by synthesized peptide consisting of 17 amino acids were examined. Vbeta4+ T cells with similar Vbeta CDR3 motifs that infiltrate the heart and pericardial space may recognize the same epitope.

Amino Acid Sequence↗
PubMed1998

Dual isotope SPECT in malignant Jacod's syndrome.

A case is presented of metastatic tumor causing Jacod's syndrome: total ophthalmoplegia, blindness, and trigeminal neuralgia. Abnormal soft tissue invading the orbital apex, anterior clinoid process, and cavernous sinus was difficult to assess by CT and MRI, but dual-isotope SPECT including Tc-99m HMDP bone imaging and Tl-201 tumor imaging strongly suggested that the cause of this rare syndrome was a small metastatic tumor. Although the therapeutic effect was also difficult to assess by anatomic imaging alone, dual-isotope SPECT after radiation therapy showed a decline of tumor viability.

Aged↗
PubMed1998

Recovery from complete atrioventricular block caused by idiopathic giant cell myocarditis after corticosteroid therapy.

Giant cell myocarditis (GCM) is a rapidly progressive disease that leads to ventricular tachycardia or high-grade atrioventricular (A-V) block, frequently requiring a pacemaker. A 64-year-old woman developed syncope as a result of idiopathic GCM with A-V block. She required both a temporary and a permanent pacemaker. Two-dimensional echocardiography showed severely reduced wall motion. There was no histologic or clinical evidence to suggest sarcoidosis. Despite treatment with diuretics and an angiotensin-converting enzyme inhibitor, exertional dyspnea persisted. She received prednisolone 4 months after the onset of complete A-V block in the late phase of GCM. Prednisolone improved A-V nodal conduction in spite of the fact that there was no influence from LV wall motion, and sinus rhythm has continued for more than 2 years. In this patient, prednisolone was effective in the treatment of GCM.

Anti-Inflammatory Agents↗
PubMed1998

Glomerular vascular changes in KK-Ay mice with early diabetes: scanning electron microscopy of vascular resin casts.

Vascular changes, the angioarchitecture of renal glomerular fine vessels in early diabetic KK-Ay mice of 4 months of age were examined by scanning electron microscopy of corrosion casts. Histologically, enlargement of glomeruli and dilation of glomerular capillaries were found. In resin cast specimens, glomeruli with diabetes were larger than normal, and an increase in diameter of the glomerular vessels was found in diabetic mice. No capillary proliferation, distortion of glomerular vessels and destruction of glomerular capillary loops were found in diabetic mice. The increased vascular diameter may explain the increase in blood flow in the glomeruli, affecting kidney function in early diabetes.

Animals↗
PubMed1998

Histological changes in the endometrial arterioles during postpartum offthe Chinese hamster (Cricetulus griceus).

The morphology of the uterine wall in the postpartum Chinese hamster (Cricetulus griceus) was studied with particular reference to the changes in the arterioles in the mesometrial endometrium. At day 0 postpartum, the endometrial arterioles were characterized by the appearance of trophoblastic giant cells plugging ruptured arterioles. On days 1 to 3 postpartum, the giant cells were replaced by epitheloid cells. On days 4 to 5 postpartum, the epitheloid cell mass was invaded by fibroblasts to occlude the arterial lumens. On days 6 to 7 postpartum, endometrial regeneration was completed. The giant cell might play a role in hemostasis immediately after parturition.

Animals↗
PubMed1998

Induction of DNA fragmentation by total-body irradiation in murine liver.

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.

Animals↗
PubMed1998

Changes in telomerase activity of advanced cancers of oral cavity and oropharynx during radiation therapy: correlation with clinical outcome.

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.

Aged↗
PubMed1998

Radiation kills human peripheral T cells by a Fas-independent mechanism.

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.

Antibodies, Monoclonal↗
PubMed1998

Cytotoxicity of Fas ligand against lymphoma cells with radiation-induced Fas antigen.

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.

Antineoplastic Agents↗
PubMed1998

Effects of irradiation on telomerase activity in human lymphoma and myeloma cell lines.

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.

Cell Line, Tumor↗
PubMed1997

Characterization of cytokine and iNOS mRNA expression in situ during the course of experimental autoimmune myocarditis in rats.

Ribonuclease protection assay was used to demonstrate mRNA expression of several cytokines as well as inducible NO synthase (iNOS), constitutive endothelial NO synthase (cNOS) and perforin in the myocardium during the course of experimental autoimmune myocarditis (EAM) in rats. Interleukin 2 (IL-2) appeared in the initial inflammatory phase (day 14), subsided in the maximum inflammatory phase (day 19) and disappeared by the recovery phase (day 25). mRNA of IL-3 beta, interferon gamma INF-gamma and tumor necrosis factor alpha (TNF-alpha) were detected only in the maximum inflammatory phase and iNOS also appeared for several days at this time. In contrast. IL-10 mRNA was detected after the maximum inflammatory stage and persisted into the recovery phase (days 25-36). Although transforming growth factor beta 1 (TGF-beta 1) could be detected in all phases, the expression was markedly enhanced in the maximum inflammatory phase and gradually diminished (around day 36) to basal levels. Perforin mRNA was not detected at any point in the disease. Besides macrophages and CD4 T cells, a number of neutrophils were found in the myocardium especially at peak inflammatory stage. We suggest that antigen (Ag) primed Ag presenting cells or macrophages interact with T cells (Th1) to produce IL-2 and subsequent IFN-gamma, which further activates macrophages in the myocardium. Consequently, TNF-alpha and iNOS may inflict tissue damage to myocardium. It is also suggested that TGF-beta) and one representative Th2 cytokine, IL-10, help inhibit inflammation. These findings suggest that Th1 and Th2 cytokines are produced at different stages of EAM and modulate the inflammation and the course of EAM.

Animals↗
PubMed1997

Expression of fas (CD95/APO-1) antigen induced by radiation therapy for diffuse B-cell lymphoma: immunohistochemical study.

Most malignant lymphomas show relatively high degrees of radiosensitivity, in which apoptosis has been shown to play an important role. Recently, the Fas (CD95/APO-1)/Fas ligand system has been identified as a key regulator of apoptosis in some types of lymphoma cell lines. In this study, we aimed to determine whether Fas antigen expression is induced by radiotherapy for malignant lymphoma and to clarify its possible correlation with the therapeutic effect of radiation therapy. Fifty-six patients with tumors of the tongue, oropharynx, and maxillary sinus were examined; four were confirmed as malignant lymphoma, and the rest were identified as squamous cell carcinoma. After obtaining the patients' informed consent, biopsies were performed before treatment and at doses of 4, 10, and 20 Gy of radiotherapy, and specimens were preserved in liquid nitrogen until further examination. Serial sectioning of 6 micrometer was performed using a cryostat, and samples were immunohistochemically stained using the streptoavidin-biotin peroxidase method and a monoclonal antibody against Fas. Two of the four patients with malignant lymphoma showed Fas antigen expression on their tumor tissue at 4 and 10 Gy of radiotherapy. These tumors showed high radiosensitivity and disappeared at a dose of 20 Gy of radiotherapy. In samples from these two patients, DNA ladder formation was identified at 10 Gy. In 52 squamous cell carcinomas, staining for the Fas antigen showed negative or only slightly positive results. However, in one of the cases of squamous cell carcinoma, lymphocytes infiltrating into cancer tissue showed Fas antigen expression at 4 Gy of irradiation, and these lymphocytes disappeared on the tumor tissue at 10 Gy. Therefore, the high radiosensitivity of malignant lymphoma among our samples could be explained by the overexpression of Fas antigen induced by small doses of radiation therapy, and Fas ligand could be produced by infiltrating lymphocytes or may be expressed simultaneously on the lymphoma cells.

Aged↗