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Biomedical subjects

T Yahata

Publications and source records attributed to T Yahata.

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

The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells.

The natural killer T (NKT) cell ligand alpha-galactosylceramide (alpha-GalCer) exhibits profound antitumor activities in vivo that resemble interleukin (IL)-12-mediated antitumor activities. Because of these similarities between the activities of alpha-GalCer and IL-12, we investigated the involvement of IL-12 in the activation of NKT cells by alpha-GalCer. We first established, using purified subsets of various lymphocyte populations, that alpha-GalCer selectively activates NKT cells for production of interferon (IFN)-gamma. Production of IFN-gamma by NKT cells in response to alpha-GalCer required IL-12 produced by dendritic cells (DCs) and direct contact between NKT cells and DCs through CD40/CD40 ligand interactions. Moreover, alpha-GalCer strongly induced the expression of IL-12 receptor on NKT cells from wild-type but not CD1(-/-) or Valpha14(-/-) mice. This effect of alpha-GalCer required the production of IFN-gamma by NKT cells and production of IL-12 by DCs. Finally, we showed that treatment of mice with suboptimal doses of alpha-GalCer together with suboptimal doses of IL-12 resulted in strongly enhanced natural killing activity and IFN-gamma production. Collectively, these findings indicate an important role for DC-produced IL-12 in the activation of NKT cells by alpha-GalCer and suggest that NKT cells may be able to condition DCs for subsequent immune responses. Our results also suggest a novel approach for immunotherapy of cancer.

Adjuvants, Immunologic↗
PubMed1999

The essential role of phorbol ester-sensitive protein kinase C isoforms in activation-induced cell death of Th1 cells.

Th1 and Th2 cells, which were induced from naive T cells of TCR-transgenic mice, showed differential sensitivity to activation-induced cell death (AICD) triggered by stimulation with anti-CD3 monoclonal antibody. The Th1 cells showed more rapid AICD than Th2 cells. This accelerated AICD of Th1 cells was strongly blocked by protein kinase C (PKC) inhibitors (H-7 or GF 109203X). Moreover, long-term treatment of Th1 cells with phorbol 12-myristate 13-acetate (PMA) caused the abrogation of anti-CD3-induced AICD in parallel with the disappearance of PMA-sensitive PKC isoforms such as PKC alpha, gamma, epsilon and theta. Therefore, it was clearly demonstrated that PMA-sensitive PKC isoforms are essential for AICD of Th1 cells. The different susceptibility to AICD between Th1 and Th2 cells was not due to their differential expression levels of PMA-sensitive PKC isoforms but appeared to be due to their differential requirement for PMA-sensitive isoforms in the up-regulation of Fas ligand which is involved in suicide killing of activated Th1 cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Association of vitamin D and estrogen receptor gene polymorphism with the effect of hormone replacement therapy on bone mineral density in Japanese women.

OBJECTIVE: We studied whether vitamin D receptor and estrogen receptor gene polymorphism is associated with the effect of hormone replacement therapy on lumbar-spinal bone mineral density in Japanese women. STUDY DESIGN: The subjects were 82 Japanese women aged 40 to 64 years (49.7 +/- 0.6 years, mean +/- SEM) who had taken hormone replacement therapy for >1 year. Genomic deoxyribonucleic acid was extracted from blood and analyzed for restriction fragment length polymorphism with the restriction endonucleases Taq I, Apa I, and Fok I for vitamin D receptor and Pvu II and Xba I for estrogen receptor. RESULTS: The subjects with genotype TT had a significantly higher percentage change in bone mineral density per year than those with the Tt genotype (2.8% +/- 0.6% vs -0.8% +/- 1.4%, P =.019). The serum level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen decreased by 13% during 1 year of hormone replacement therapy in subjects with the TT genotype (P =. 001) but did not change in women with the Tt genotype. In multiple regression analysis including age, height (centimeters), weight (kilograms), and polymorphisms of the vitamin D receptor and estrogen receptor genes, only age and Taq I polymorphism of the vitamin D receptor gene were associated independently with change in bone mineral density (P =.001 and.004, respectively). CONCLUSION: Taq I polymorphism of the vitamin D receptor gene is associated with the effect of hormone replacement therapy on lumbar-spinal bone mineral density and bone resorption markers in Japanese women. Analysis of the vitamin D receptor alleles may prove useful for selection of the optimum therapy for osteoporosis management.

Adult↗
PubMed1999

The quantitative and qualitative defect of CD4+ CD45RO+ memory-type T cells are involved in the abnormality of TH1 immunity in atopic dermatitis patients.

Peripheral blood mononuclear cells (PBMCs) obtained from atopic dermatitis (AD) patients produced low levels of IFN-gamma in response to Dermatophagoides farinae antigen (Der f Ag) plus IL-2 or OKT3 MoAb in contrast with PBMCs obtained from healthy donors. The reduced IFN-gamma production in AD patients' T cells appeared to be derived from the defect of CD4+ T cells but not CD8+ T cells. Indeed, from the cytoplasmic staining analysis of cytokines, it was demonstrated that the frequency of IFN-gamma producing CD4+ T cells (TH1 cells) in AD patients was markedly lower than that of healthy donors. From the phenotypic analysis using flow cytometry, it was also found that the number of CD4+ CD45RO+ memory type T cells was significantly reduced in AD patients compared with that of healthy donors. In addition to quantitative defect of memory type CD4+ T cells, functional defect of CD4+ CD45RO+ memory type T cells was also demonstrated in AD patients. Enriched CD4+ CD45RO+ T cells obtained from AD patients, who exhibited greatly reduced delayed-type hypersensitivity (DTH) response in tuberculin test, showed no significant TH1 immunity in terms of IFN-gamma production by stimulation with OKT3 MoAb or purified protein derivative (PPD). Thus, the immunological abnormality of TH1 immunity in AD patients appeared to be induced in concomitant with both the quantitative and qualitative defect of memory type CD4+ T cells.

Antibodies, Monoclonal↗
PubMed1999

Thermoregulatory responses of the inbred heat-tolerant FOK rat to cold.

The responses of inbred heat-tolerant FOK rats to cold were compared with those of Wistar King A/H (WKAH) and Std:Wistar (WSTR) strains. The fall of colonic temperature during cold exposure was unexpectedly smaller in FOK than in other groups, but the onset of shivering was delayed in FOK. Norepinephrine (NE)-induced in vivo oxygen consumption and the mitochondrial uncoupling protein 1 level of brown adipose tissue (BAT) were not different among the groups, but the cold-induced increases in in vivo oxygen consumption as well as plasma glycerol and free fatty acids were higher in FOK than in other groups. In vitro NE-induced oxygen consumption of BAT was less in FOK than WSTR, but not WKAH. The magnitude of the NE-induced increase in blood flow through BAT was higher in FOK than in other groups. These results suggest that FOK paradoxically have a high capacity for nonshivering thermogenesis in spite of their high capacity for heat tolerance, probably due to an increased lipid utilization and improved circulation of BAT.

Adaptation, Physiological↗
PubMed1999

[Extravasation of contrast media in acute subdural hematoma during three-dimensional CT angiography: a case report].

We report a case of acute subdural hematoma in which extravasation of contrast medium was demonstrated using three-dimensional computed tomographic angiography (3D-CTA). An 83-year-old man was found lying down on the floor but he was conscious. Thirty minutes later, he lost consciousness and was transferred to our hospital in a comatose state with right hemiparesis. Plain CT scan showed a left temporoparietal acute subdural hematoma with subarachnoid hemorrhage. CT scan also demonstrated an iso-density area beneath a high-density around the left Sylvian fissure. We performed an emergent 3D-CTA to rule out ruptured aneurysm as the cause of hemorrhage. However, 3D-CTA revealed no cerebral aneurysm, but extravasation of contrast medium from the cortical artery of the left temporal cortex was noted. The patient immediately underwent total evacuation of subdural hematoma by small temporoparietal craniectomy under local anesthesia. We found 3D-CTA to be a useful, less-invasive method for diagnosing the hemorrhagic cause and localizing the bleeding point. It is expected that with more routine use of 3D-CTA in patients with acute subdural hematoma, extravasation of the contrast medium will be seen more frequently. Subdural hematoma with extravasation of contrast medium required emergent surgery, and 3D-CTA findings facilitated the selection of the surgical method according to the bleeding point.

Acute Disease↗
PubMed1998

Transcriptional activating activity of Smad4: roles of SMAD hetero-oligomerization and enhancement by an associating transactivator.

Smad4 plays a pivotal role in signal transduction of the transforming growth factor beta superfamily cytokines by mediating transcriptional activation of target genes. Hetero-oligomerization of Smad4 with the pathway-restricted SMAD proteins is essential for Smad4-mediated transcription. We provide evidence that SMAD hetero-oligomerization is directly required for the Smad4 C-terminal domain [Smad4(C)] to show its transcriptional transactivating activity; this requirement obtains even when Smad4(C) is recruited to promoters by heterologous DNA-binding domains and in the absence of the inhibitory Smad4 N-terminal domain. Defined mutations of GAL4 DNA-binding domain fusion of Smad4(C) that disrupt SMAD hetero-oligomerization suppressed transcriptional activation. Importantly, we found that an orphan transcriptional activator MSG1, a nuclear protein that has strong transactivating activity but apparently lacks DNA-binding activity, functionally interacted with Smad4 and enhanced transcription mediated by GAL4 DNA-binding domain-Smad4(C) and full-length Smad4. Transcriptional enhancement by MSG1 depended on transforming growth factor beta signaling and was suppressed by Smad4(C) mutations disrupting SMAD hetero-oligomerization or by the presence of Smad4 N-terminal domain. Furthermore, Smad4(C) did not show any detectable transactivating activity in yeast when fused to heterologous DNA-binding domains. These results demonstrate additional roles of SMAD hetero-oligomerization in Smad4-mediated transcriptional activation. They also suggest that the transcriptional-activating activity observed in the presence of Smad4 in mammalian cells may be derived, at least in part, from endogenously expressed separate transcriptional activators, such as MSG1.

3T3 Cells↗
PubMed1998

Bone structural and metabolic changes at the end of pregnancy and lactation in rats.

OBJECTIVE: The objective of this study was to elucidate the net change of bone structure and metabolism in the lumbar trabecular bone of rats at the end of the pregnancy and lactation. STUDY DESIGN: Female virgin Sprague-Dawley rats aged 200 days were mated, and bone mineral density by dual-energy x-ray absorptiometry, bone histomorphometry, and serum bone metabolic markers were measured at the end of pregnancy (day 22 of pregnancy), after delivery (day 5 post partum), and at the end of lactation (day 21 post partum). RESULTS: At the end of pregnancy bone mineral density, bone volume, trabecular thickness, and serum calcium decreased; serum parathyroid hormone increased; and the histomorphometric parameters indicated that bone resorption were higher than those variables in nonpregnant rats, but bone formation was suppressed, as demonstrated by the low histomorphometric parameters and by the low serum alkaline phosphatase levels. After delivery the bone mineral density of nonlactating rats recovered rapidly, as in nonpregnant rats, but nonlactating rats showed more bone formation by histomorphometry than nonpregnant rats did. At the end of lactation, bone mineral density and serum calcium levels decreased considerably, and lactating rats showed substantial bone formation, bone resorption, and high serum alkaline phosphatase levels. The correlation between the number of pups (x) of the lactating and nonlactating groups and the bone mineral density (y, in grams per square centimeter) showed simple linear regression (y = -0.0067 . x +0.2517, r = 0.949, p < 0.0001). CONCLUSIONS: These results indicate that significant decreases occur in the trabecular bone of rats at the end of pregnancy and lactation and that lactational intensity is related to bone mineral density.

Absorptiometry, Photon↗
PubMed1998

Effect of long-term hormone replacement therapy on the bone in ovariectomized women with cancer.

OBJECTIVE: To evaluate longitudinally the effectiveness of long-term hormone replacement therapy (HRT) in preserving the bone mineral density (BMD) over a 5-year period in ovariectomized patients treated for gynecologic malignancies. METHODS: A total of 70 pre-menopausal women ovariectomized for gynecologic malignancies at our hospital were divided non-randomly into two groups: HRT (+) group (n = 59) and HRT (-) group (n = 11). HRT was administered in a sequential regimen of 0.625-1.25 mg conjugated estrogen for 24 days and 5-10 mg medroxyprogesterone acetate for 10 days. RESULTS: The BMD of the lumbar vertebrae decreased significantly in the HRT (-) group (pre-operative BMD was 91.8%, 91.0% and 91.3% at 1, 2 and 3 years post-ovariectomy), but no decrease in the BMD was observed in the HRT (+) group (pre-operative BMD was 98.4%, 99.0%, 99.4%, 98.8% and 98.7% at 1, 2, 3, 4 and 5 years post-ovariectomy); the difference in BMD between the two groups was statistically significant (P < 0.01). Serum alkaline phosphatase levels were significantly lower in the HRT (+) group than in the HRT (-) group (P < 0.01). There were four recurrences of cancer in the HRT (+) group. CONCLUSION: HRT appeared to have beneficial effects on bone metabolism by maintaining BMD for 5 years in ovariectomized patients for gynecologic malignancies.

Adult↗
PubMed1998

Lumbar bone mineral density changes during pregnancy and lactation.

OBJECTIVE: To elucidate the change of bone metabolism in the lumbar trabecular and its relationship with serum hormonal changes in pregnancy and lactation. STUDY DESIGN: In a cross-sectional study, we measured the bone mineral density (BMD) of 2-4 lumbar vertebrae of 571 puerperae at days 3-5 postpartum and 341 healthy, non-pregnant women (control subjects) of approximately the same age by dual energy X-ray absorptiometry. In a longitudinal study, we also measured the BMD of 111 puerperae at 3 and 6 months after delivery. RESULTS: The mean BMD at days 3-5 postpartum was significantly lower than that of the control (1.013+/-0.005 vs. 1.032+/-0.006 g/cm2, P = 0.019). The lactating group showed BMD decrement to 95.1+/-0.5% (n = 69) and 94.1+/-0.7% (n = 61) at 3 and 6 months postpartum, respectively, compared with days 3-5 postpartum, and the amenorrhea group showed the same tendency. The non-lactating group and resumption of menses group did not show a BMD decrement postpartum. In the lactating group, serum estradiol was significantly lower than in the non-lactating group at 3 months postpartum, serum prolactin and bone alkaline phosphatase levels were higher than in the non-lactating group at 3 and 6 months postpartum. CONCLUSIONS: Pregnancy may cause a decrease of lumbar BMD, and the lactation and amenorrhea also cause a decrease of BMD. In addition to lactation status, the ovarian dysfunction is one of the factors in bone loss during lactation.

Absorptiometry, Photon↗
PubMed1998

Decrease in the proportion of granulated CD56+ T-cells in patients with a history of recurrent abortion.

We investigated levels of CD56+ T-cells (CD3+ CD56+ cells) in peripheral circulation, which express one of the natural killer (NK) cell markers, by flow cytometry and with monoclonal antibodies in patients with a history of recurrent abortion. We compared these values with those obtained in normal women who were not pregnant as well as in normal pregnant subjects. The percentage of CD56+ T-cells in the peripheral blood of patients with a history of recurrent abortion was less than that in the non-pregnant or pregnant women. These results suggest that CD56+ T-cells with extrathymic properties may be associated with the maintenance of normal pregnancy in humans.

Abortion, Habitual↗
PubMed1998

Accumulation of IL-12-activated antitumor effector cells into lymph nodes of tumor-bearing mice.

Simultaneous administration of high dose of IL-12 into tumor-inoculated mice resulted in a marked reduction of tumor growth in parallel with the augmented generation of cytotoxic T-cells, natural killer (NK) cells and IFN-gamma-producing Th cells. We found that these IL-12-activated antitumor effector cells preferentially accumulated in peripheral lymph nodes concomitantly with lymphadenopathy. However, IL-12 rather induced disappearance of antitumor effector cells including CD4+ T, CD8+ T and NK cells from spleen in spite of inducing splenomegaly. Lymph node cells obtained from IL-12-treated B16F0-bearing mice showed a marked IFN-gamma production in response to not only IL-2, IL-12, anti CD3 mAb but also B16F0 melanoma cells. Moreover, they could lyse B16F0 melanoma cells in a long-term cytotoxicity assay. It was also confirmed that IL-12-activated IFN-gamma producing Th1 cells were accumulated in tumor local site. Thus, IL-12 appeared to have a capability of stimulating selective migration of antitumor cells into lymph nodes and tumor local sites.

Animals↗
PubMed1998

The restraint stress drives a shift in Th1/Th2 balance toward Th2-dominant immunity in mice.

When mice were physically restrained in 50-ml tubes for 24 h, a marked decrease of NK activity was demonstrated in parallel with the elevation of serum corticosterone levels. The release of mice from restraint stress resulted in the recovery of NK activity, with a decrease of serum corticosterone levels within 48 h. Using this stress model, we also investigated the influence of restraint stress on mouse Th1/Th2 balance. Consistent with the decrease of NK activity, IFN-gamma production of mouse spleen cells greatly reduced after suffering from restraint stress. In contrast, the IL-4 producing ability of spleen cells was not so much affected by restraint stress. These results initially indicated that stress may induce the skewing of the Th1/Th2 balance toward Th2-dominant immunity, which stimulates the occurrence of infectious diseases and allergic disorders.

Animals↗
PubMed1998

Reconstitution of immune systems in RAG2-/- mice by transfer with interleukin-12-induced splenic hematopoietic progenitor cells.

The administration of a high dose of IL-12 into the mice resulted in the induction of splenomegaly. From the flow cytometry analysis of cellularity in an enlarged spleen, it was demonstrated that Thyl.2-CD45RB-c-Kit + Sca-1 + Lin- hematopoietic progenitor cells markedly increased in IL-12-administered mouse spleen compared with untreated mouse spleen. The IL-12-induced hematopoietic progenitor cells showed a greatly enhanced colony-forming activity in CFU-granulocyte/macrophage (CFU-GM), blast-forming units-erythroid (BFU-E) and CFU-spleen (CFU-S) assay. Moreover, it was initially demonstrated that the transfer of IL-12-induced splenic hematopoietic progenitor cells into immunodeficient RAG2-/- mice caused a complete reconstitution of their immune functions including T- and B-cell-mediated immunity. Thus, the evidence that IL-12 has a capability of inducing hematopoietic progenitor cells possessing stem cell-like activity in vivo, indicated another important immunomodulating activity of IL-12 in immunotherapy.

Animals↗
PubMed1998

Effects of progestins on the metabolism of cancellous bone in aged oophorectomized rats.

The effects of progestins on bone loss in female oophorectomized (ovx) rats were evaluated. One-year-old Sprague-Dawley rats were divided into eight groups: (1) beginning controls (control); (2) sham-operated controls (sham); (3) ovx; (4) ovx treated with estrogen (ovx + E); (5) ovx treated with progesterone (ovx + P); (6) ovx treated with estrogen and progesterone (ovx + E + P); (7) sham group treated with estrogen (sham + E); and (8) sham group treated with progesterone (sham + P). Immediately after surgery, the rats in the hormone injected groups were subcutaneously (s.c.) injected daily for 15 weeks with estrogen (17-beta-estradiol, 0.01 mg/kg in ethanol), or progesterone (4-pregnene-3,20-dione, 0.1 mg/kg in ethanol), or both. At the end of 15 weeks, the bone mineral density (BMD) and bone histomorphometry of the rats' lumbar vertebrae and serological parameters were measured. In the sham, ovx, and ovx + P groups, treatment with progesterone alone did not maintain the BMD in the lumbar vertebrae, but in the ovx + E and ovx + E + P, sham + E, and sham + P groups, progesterone did not inhibit the action of estrogen in the aged ovx rat model. BMD in the sham + P group was significantly higher than in the sham group (270.8+/-10.8 mg/cm2 versus 253.6+/-10.2 mg/cm2; p < 0.01). Bone histomorphometry revealed that bone volume (BV/TV) increased more in the ovx + E + P group than in the ovx + E group and more in the sham + P group than in the sham group, but not significantly. The ovx + E, ovx + E + P, sham + E, and sham + P groups showed no significant differences in the bone formation and resorption parameters, but the bone formation variables tended to increase in the ovx + E + P and sham + P groups. We concluded that progesterone alone cannot prevent bone loss or the increase in turnover after ovx and that estrogen, not progesterone, accounted for all of the bone activity in this study. It seems doubtful that progesterone inhibits the action of estrogen, and in fact may have a beneficial effect on bone metabolism.

Animals↗
PubMed1998

Laparoscopic management of rudimentary horn pregnancy. A case report.

BACKGROUND: Rudimentary uterine horn pregnancy is a very rare condition. Removal of a rudimentary horn is required as soon as a pregnancy is confirmed because most pregnancies in a rudimentary uterine horn rupture in the first or second trimester. CASE: A 22-year-old woman was admitted to our hospital because an ectopic pregnancy was suggested by ultrasonographic examination at another hospital. A rudimentary uterine horn pregnancy was suspected from transvaginal ultrasonography. The patient was treated with laparoscopic surgery at 7 weeks of gestation. The pregnant rudimentary horn was removed laparoscopically by use of an automatic stapling device. The postoperative course was uneventful. CONCLUSION: This is the first report of laparoscopic resection of a pregnant rudimentary uterine horn. Laparoscopic management of such a pregnancy may reduce operating time and peritoneal damage.

Abortion, Induced↗
PubMed1997

Manipulation of Th1/Th2 balance in vivo by adoptive transfer of antigen-specific Th1 or Th2 cells.

We have investigated the possibility that the Th1/Th2 balance in vivo may be modulated by adoptive transfer of Th1 or Th2 cells induced in vitro. Thl cells were induced from I-Ad-binding OVA323-339-specific T-cell receptor-transgenic (TCR-Tg) mouse spleen cells by culturing with OVA323-339 peptide and antigen presenting cells (APC) in the presence of IL-2, IL-12 and anti-IL-4 mAb. Th2 cells were induced from TCR-Tg mouse spleen cells by culturing with IL-2, IL-4 and anti-IL-12 mAb in addition to OVA323-339 plus APC. Immunomodulating activities of both Th1 and Th2 cells were determined by their effect on delayed type hypersensitivity (DTH) responses or cytokine production. No significant DTH responses (footpad swelling) were observed in untreated BALB/c mice following a single injection of OVA323-339-pulsed syngeneic spleen cells. However, adoptive transfer of Th1 cells into BALB/c mice induced strong dose dependent DTH responses in response to I-Ad-bound OVA323-339 but not unrelated peptide. In contrast, only slight DTH responses were detected in BALB/c mice transferred with Th2 cells. In parallel with the DTH responses, increased levels of serum IFN-gamma were demonstrated in mice adoptively transferred with Th1, while no significant increase was observed in Th2-transferred mice. In vitro analysis also demonstrated that both spleen cells and popliteal lymph node cells prepared from Th1-transferred mice showed Th1-type cytokine production, while cells obtained from Th2-transferred mice revealed Th2-dominant cytokine production. Such immune deviation induced by antigen-specific Th1 cells was demonstrated up to three months after cell transfer. Therefore, it may be possible to manipulate the Th1/Th2 balance in vivo by adoptive transfer of antigen-specific Th1 or Th2 cells.

Adoptive Transfer↗