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T Yahata

Publications and source records attributed to T Yahata.

At least 55 records · Page 3Linked to original sources
PubMed1997

The role of phorbol ester-sensitive protein kinase C isoforms in lymphokine-activated killer cell-mediated cytotoxicity: dissociation between perforin-dependent and Fas-dependent cytotoxicity.

Treatment of lymphokine-activated killer (LAK) cells with phorbol ester (PMA) caused the downmodulation of LAK activity concomitantly with the inhibition of serine esterase (SE) release, which has been shown as a marker for perforin-dependent cell-mediated cytotoxicity. The reduction of perforin-dependent LAK activity by PMA-treatment appeared to be due to the disappearance of PMA-sensitive protein kinase C (PKC) isoforms such as PKC alpha, gamma, epsilon, theta. In contrast, Fas-mediated LAK activity was refractory against PMA-induced downregulation. Treatment of LAK cells with PMA caused a disappearance of cytotoxicity against Fas L5178Y tumor cells, while cytotoxicity against Fas+ transfectants was not affected by PMA treatment. Moreover, Fas-mediated LAK activity of perforin-knockout mice was not inhibited by PMA treatment. These results clearly demonstrated that Fas-mediated cytotoxicity could be dissociated from perforin-mediated cytotoxicity by their different requirement of PMA-sensitive PKC isoforms.

Animals↗
PubMed1997

Involvement of IL-4-producing Vbeta8.2+ CD4+ CD62L- CD45RB- T cells in non-MHC gene-controlled predisposition toward skewing into T helper type-2 immunity in BALB/c mice.

It was found that freshly isolated BALB/c CD4+ T cells produced high levels of IL-4 and IL-10 in response to immobilized anti-CD3 mAb, while C57BL/6 CD4+ T cells produced low amounts of IL-4 and IL-10. The high IL-4-producing ability of BALB/c mice was demonstrated to be genetically dominant and it was controlled by non-MHC gene (or genes). The cells responsible for IL-4 production in BALB/c mice were defined as TCRVbeta8.2+ CD4+ CD62L- CD45RB- memory-type T cells, which were distinct from NK1.1+ CD4+ NKT cells. Although these memory-type T cells were also detected in C57BL/6 mouse spleen at the same frequency, they showed a functionally different property from BALB/c CD4+ CD62L- CD45RB- T cells in terms of IL-4 production. The fact that germfree BALB/c mouse spleen cells also produced high levels of IL-4 suggested that the IL-4 producer in BALB/c mice might be developed under the influence of unknown factors other than environmental Ags. The CD4+ CD62L- CD45RB- T cells obtained from BALB/c mice accelerated the development of IL-4-producing memory-type CD4+ T cells from CD4+ CD62L+ CD45RB+ naive T cells prepared from OVA-specific TCR-transgenic mice. Therefore, IL-4-producing CD4+ CD62L- CD45RB- T cells might play an important role in the preferential induction of Th2-dominant immunity in BALB/c mouse strain.

Animals↗
PubMed1997

Primary choriocarcinoma of the uterine cervix: clinical, MRI, and color Doppler ultrasonographic study.

Primary choriocarcinoma of the uterine cervix was diagnosed in a 38-year-old Japanese woman 4 months after a normal vaginal, term delivery. The patient had experienced irregular genital bleeding for several weeks. A cervical polypoid tumor was detected by visual inspection 4 months after delivery. Magnetic resonance imaging (MRI) and color Doppler ultrasonography revealed a hypervascular tumor (6 cm) in the uterine cervix. The patient's urinary level of human chorionic gonadotropin (hCG) was 128,000 IU/L. Histological examination of a biopsy of the cervical tumor showed choriocarcinoma. After completion of 2 courses of chemotherapy, the patient underwent a total abdominal hysterectomy. Histological examination of uterus showed no evidence of choriocarcinoma. At present, the patient is free of disease. MRI and color Doppler ultrasonography were useful for diagnosis by detecting the abundant blood flow and central necrosis of the cervical tumor.

Adult↗
PubMed1997

The capillarity of the subendocardium of left ventricle in rats reared at a low temperature for many generations.

The cardiac capillarity in adult rats reared at 5 degrees C for 68 generations was studied with a double staining method of alkaline phosphatase and dipeptidylpeptidase IV. Capillary density, proportions of arteriolar, intermediate and venular capillary portions and capillary domain area were measured in the left ventricular wall. Compared with the control rats which had been brought back from the low temperature at the 12th generation and reared at 25 degrees C since then, the heart and the cardiac cells were hypertrophied, total capillary density increased and the capillary domain areas were reduced along the capillary path from the arteriolar to venular capillary portions. The number of the venular capillary portions showed no significant change but the arteriolar and intermediate capillary portions significantly increased. All these changes suggest that the cardiac capillary network was better developed in the cold-reared rats than in control rats. In the cold-adapted rats the hypertrophic changes in cardiac cells are thus accompanied by improvements in the oxygen delivery capacity. This adaptation provides a basis for the maintenance of increased thermogenesis in many organs. The changes cannot be established by several weeks exposure to low temperature, but only after rats have been bred in a cold room for generations.

Adaptation, Physiological↗
PubMed1997

Capillary geometry in the soleus muscle of rats cold-acclimatized for 68 generations.

The effects of chronic cold exposure on soleus muscle capillarity were examined, particularly in terms of the distribution of arteriolar and venular capillaries and their capillary domain area (CDA) in adult rats exposed to cold for 68 generations (CG; n = 6). These parameters were compared with those obtained from control rats (CON; n = 5) and deacclimatized rats (DCG; n = 4), reared in thermoneutral temperature after being reared for 11 generations in cold. Morphometric data were obtained from muscle cross sections exposed to a double-staining method that stained the arteriolar and venular portions of capillaries blue and red, respectively. In CG, the capillary densities of arteriolar and venular capillaries were significantly greater than that of both CON and DCG (P < 0.05). The CDA of arteriolar, intermediate and venular portions in CG was significantly smaller by 15, 14 and 13%, respectively, than those of respective portions in CON (P < 0.05). Although CDA of arteriolar and venular capillary portions was also smaller in DCG than in CON, the degree of reduction was less in DCG than in CG. The succinate dehydrogenase activity of soleus muscle was significantly greater in CG than in both CON and DCG (P < 0.05). These results suggest that adaptive changes in the oxygen transport system, identified as an increase in the number of arteriolar capillaries and a reduction in the diffusion distance for oxygen, were observed in the soleus muscle after chronic cold exposure. These changes may improve the effective oxygen supply to muscle tissues and enable muscle tissues to promote thermogenesis in the cold atmosphere.

Acclimatization↗
PubMed1997

Direct intratumoral gene transfer of the herpes simplex virus thymidine kinase gene with DNA-liposome complexes: growth inhibition of tumors and lack of localization in normal tissues.

To constitute the site-specific expression of the herpes simplex virus thymidine-kinase (HSV-TK) gene in tumor cells, we have assessed the promoter function of the simian virus 40 (SV40) promoter and the 5'flanking region of c-erbB-2 gene using a luciferase-expressing reporter plasmid. After the transfection of the luciferase plasmid directed by the promoter region of c-erbB-2 gene, a large amount of luciferase activity was observed in c-erbB-2-expressing cells (Colo201, MCF-7, and HEC1-A), while none was detected in cells with no expression of c-erbB-2 protein (HRA and KF cells). On the other hand, a high level of luciferase activity was detected in all tumor cell lines tested, when the transfection was performed with SV40 promoter. The repeated transfection of the liposome-conjugated HSV-TK gene regulated by the SV40 promoter or by the promoter region of c-erbB-2 gene with cultivation in 100 micrograms/ml of aciclovir for 5 days in vitro resulted in growth inhibition for all four cell lines examined or for only c-erbB-2-expressing cells in the presence of SV40 promoter or c-erbB-2 promoter, respectively. Finally, direct injection of the DNA-liposome complex into established tumors in the presence of 50 mg/kg of aciclovir led to significant tumor volume reduction in all three tumors tested when SV40 promoter was employed. However, this anti-tumor effect was noted only in c-erbB-2-positive cells (Colo201 cells) upon intratumoral injection of HSV-TK gene regulated by c-erbB-2 promoter. In the case of intratumoral gene transfer, foreign DNA was detected in only one of seven mice by polymerase chain reaction (PCR) analysis performed 7 days following injection. When PCR analysis was carried out at 14 or 21 days following injection, no DNA signal was found at all. However, DNA was detected in several normal tissues at all three times tested in the case of intravenous injection. No abnormalities were seen in histologic examinations of normal tissues or in serum biochemical parameters following DNA liposome delivery. These results suggest that the direct gene transfer of HSV-TK gene regulated by tumor-specific transcriptional units may be one of the most clinically promising of the selective genetic strategies against cancer.

Acyclovir↗
PubMed1997

Bronchial responsiveness to inhaled histamine in canine pulmonary congestion.

To elucidate the role of bronchial hyperresponsiveness (BHR) in pulmonary congestion, an inhaled histamine provocation test was performed in dogs with acute pulmonary congestion, and the role of vagal nerve activity and arachidonic acid metabolites on bronchial responsiveness was evaluated. We assessed BHR with the provocation concentration of histamine causing a 100% increase in pulmonary resistance (PC100) in an openchest anesthetized and tracheotomized canine model before and after left atrial balloon inflation. Twenty-two mongrel dogs (8-14 kg) were anesthetized with sodium thiopental (15-20 mg/kg) and mechanically ventilated with positive end-expiratory pressure at 3 cmH2O. A Foley catheter was inserted into the left atrium to cause pulmonary congestion, in which mean left atrial pressure was increased to 18 mmHg. In 6 dogs, histamine provocation was examined before and after pulmonary congestion was effected. Intravenous indomethacin (1 mg/kg) administration and vagotomy were performed in 5 dogs. In pulmonary congestion, PC100 was significantly decreased both before and after vagotomy and after indomethacin administration. We conclude that pulmonary congestion augments bronchial responsiveness to inhaled histamine and that neither vagotomy nor indomethacin administration prevents bronchial hyperresponsiveness in pulmonary congestion. These findings suggest that bronchial hyperresponsiveness in pulmonary congestion is related to another factor such as bronchial edema.

Administration, Inhalation↗
PubMed1996

Functional characterization of NK1.1 + Ly-6C+ cells.

It was found that NK1.1+ cells were subdivided by their different expression pattern of Ly-6C antigen. To characterize their functional significance in immunoregulation, we separated NK1.1 + Ly6C+ cells and NK1.1 + Ly-6C- cells from C57BL/6 mouse nylon-passed spleen cells by FACStar. Both NK1.1 + Ly-6C+ and NK1.1 + Ly-6C- cells responded to the stimulation with IL-2 plus IL-12 and showed strong cytotoxicity against YAC-1 cells. However, these cells revealed different ability in terms of IFN-gamma production. Only NK1.1 + Ly-6C+ cells, but not NK1.1 + Ly-6C- cells, cultured with IL-12 alone or IL-2 plus IL-12, produced high levels of IFN-gamma. Flow cytometric analysis demonstrated that NK1.1 + Ly-6C+ cells consisted of NK1.1 + CD3-Ly-6C+ NK cells and NK1.1 + CD3 + Ly-6C+ NKT cells. Therefore, we further separated these two populations from NK1.1 + Ly-6C+ cells to define their functions. Although, both NK1.1 + CD3-Ly-6C+ NK cells and NK1.1 + CD3+ NKT cells showed the same level of cytotoxicity. It was clearly demonstrated that NK1.1 + CD3+Ly-6C+ NKT cells were major immunoregulatory cells to produce IFN-gamma in respond to IL-12 alone or IL-2 plus IL-12.

Animals↗
PubMed1996

Physiological dose of estrogen regulates extrathymic T cells in female mice.

Bilateral ovariectomy was performed in female C57BL/6 mice to investigate whether extrathymic T cells in the liver are regulated by physiological doses of estrogen or progesterone. Extrathymic T cells were identified using a two-color immunofluorescence test for CD3 and interleukin-2 receptor beta-chain (IL-2R beta) antigens. The T cells were identified as intermediate CD3+ cells with a high expression of IL-2R beta. It was further demonstrated that the proportion and number of intermediate CD3+ cells decreased in response to ovariectomy, an effect that was countered by estrogen administration. These results suggest that the activation of extrathymic T cells may be regulated by physiological levels of estrogen.

Animals↗
PubMed1996

Recurrent placental site trophoblastic tumor of the uterus: clinical, pathologic, ultrastructural, and DNA fingerprint study.

Placental site trophoblastic tumor is a rare disease. Most benign cases of this disease show a few mitotic figures of the tumor while recurrent cases usually have more than 5 mitoses per 10 high-power fields. The present case was primarily treated by hysterectomy and chemotherapy and had 2 mitoses in 10 high-power fields. After 1 years and 4 months of therapy the patients was diagnosed as ovarian metastasis because of gradually increasing serum beta-human chorionic gonadotropin (hCG) level and abnormally high fluid levels of beta-hCG and human placental lactogen (hPL) punctured from her cystic ovarian tumor. This recurrent case was further treated with another regimen of chemotherapy for 7 courses, and the serum beta-hCG level had decreased at present. This report describes the recurrent case and discusses the histology of a few mitotic figures, electron microscopic findings, and results of the DNA fingerprint analysis of the primary tumor.

Adult↗
PubMed1996

Application of interleukin 12 to antitumor cytokine and gene therapy.

In vivo administration of interleukin 12 (IL-12) at 2000 U/mouse induced IL-12-activated killer (IL-12AK) cells in parallel with an elevation in serum interferon-gamma (IFN-gamma) activity. Although NK1.1+CD3- natural killer cells are the major precursor of IL-12AK cells, asialoGM1+CD8+ T-cells were also demonstrated to be novel precursors. Such anomalous killer cells may play an important role in the early stages of the host defense mechanisms against tumors. It was also shown that IL-12 is effective in inducing tumor-specific cytotoxic T-lymphocytes. Consistent with these data, IL-12 had marked activity against various kinds of established tumors when given systemically. Mice cured of tumors by IL-12 treatment acquired tumor-specific T-cell immunity. Moreover, we initially demonstrated that IL-12 was effective in preventing and inhibiting the growth of primary tumors induced by the chemical carcinogen methylnitrosourea using c-Ha-ras transgeneic mice. Finally, we investigated the application of IL-12 to antitumor gene therapy. Transfer of the IL-12 gene into A20 B-lymphoma cells resulted in the continuous production of IL-12 and caused abrogation of in vivo tumorigenicity. Tumor cells transfected with the IL-12 gene are potentially a good tool as a tumor vaccine, as they effectively induced IL-12AK cells, IFN-gamma production, and tumor-specific protective immunity. Although B16-BL-6 melanoma cells, which are a highly metastatic subclone of B16 melanoma cells, showed resistance to IL-12 gene therapy, combination therapy with the B7-1 gene and systemic IL-12 administration almost completely inhibited tumor metastasis. Similar results were obtained using B16-BL-6 melanoma cells transfected with both B7-1 and IL-12 genes. These results suggest that IL-12 is a promising cytokine for antitumor cytokine and gene therapy.

Animals↗
PubMed1996

A pivotal role of IL-12 in Th1-dependent mouse liver injury.

Intravenous injection of Propionibacterium acnes and lipopolysaccharide (LPS) with a 7 day interval caused CD4+ T cell-dependent severe liver injury in the C57BL/6 (H-2b) mouse strain. In contrast, BALB/c (H-2d) mice were resistant to P. acnes and LPS-induced liver injury. The different susceptibilities of the two mouse strains to liver injury appeared to be closely correlated with their different abilities to produce IFN-gamma after P. acnes priming. Namely, the sensitive C57BL/6 mouse strain produced a significant level of IFN-gamma 7-10 days after P. acnes injection, whereas no significant amount of serum IFN-gamma was detected in the resistant BALB/c mouse strain. The important role of IFN-gamma in liver injury was demonstrated from the finding that in vivo administration of anti-IFN-gamma mAb abrogated P. acnes and LPS-induced liver injury in C57BL/6 mice. Moreover, it was demonstrated that in vivo administration of recombinant IL-12, a key cytokine for the induction of IFN-gamma, into mice induced P. acnes and LPS-induced liver injury in the resistant BALB/c mouse strain. Conversely, in vivo administration of anti-IL-12 mAb blocked the development of liver injury in the sensitive C57BL/6 mouse strain. Moreover, it was demonstrated that the failure of the induction of liver injury in BALB/c mice appeared to be derived from the lack of expression of IL-12 at the local site of liver in P. acnes-primed mice. These results strongly indicated that endogenous IL-12, which stimulates Th1-dominant cellular immunity and IFN-gamma production, may be an essential cytokine on the course of T cell-dependent liver injury.

Animals↗
PubMed1996

Case report: an exaggerated placental site with a cervical pregnancy.

An exaggerated placental site (EXPS) is an exuberant nonneoplastic proliferation of the intermediate trophoblast at the implantation site. We had a case of an EXPS with a cervical pregnancy. We report on this case, including the patient's clinical course and immunohistological findings.

Adult↗
PubMed1995

Phenotypic and functional characteristics of in vivo-induced interleukin-12-activated killer cells.

A single i.p. administration of IL-12 (2000 U/mouse) into the mice caused the elevation of serum IFN-gamma activity and the generation of killer cells which can lyse various kinds of tumor cells including both NK-sensitive and -resistant tumor cells. Such in vivo induced killer cells were not detected in the mice treated with the same dose of IL-2. The generation of IL-12-activated killer cells (IL-12AK) peaked at day 1 and sustained their cytotoxicity until day 3 after IL-12 administration. The generation of IL-12AK was inhibited by in vivo administration of anti-asialo GM1 (ASGM1) Ab but not anti-CD4 or anti-CD8 mAbs, suggesting that the precursor cells for IL-12AK were ASGM1+CD4-CD8- NK cells. The phenotypic characterization of in vivo induced effector cells with IL-12AK activity was carried out by separating the cells with FACStar. The IL-12AK activity was highly enriched in ASGM1+CD4-8- or NK1.1+CD4-8- NK cells, but not in CD8+ T cells and CD4+ T cells. The IL-12AK cells were also generated in tumor-inoculated mice. In parallel with the in vivo generation of IL-12AK generation, the growth of i.p. inoculated MBL-2 lymphoma cells was markedly inhibited by the administration with IL-12. The in vivo antitumor activity of IL-12 was blocked by the administration of anti-ASGM1 but not anti-CD4 or anti-CD8 mAbs in concomitant with the decrease of IL-12AK generation. From these results, it was indicated that ASGM1+NK1.1+CD4-8- NK type IL-12AK cells might play an important role in IL-12-induced local therapy of tumor in vivo.

Animals↗