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T Yamamura

Publications and source records attributed to T Yamamura.

At least 109 records · Page 6Linked to original sources
PubMed1998

[Significance of p53 and VEGF expression in liver metastasis from colorectal cancer].

We examined the significance of expression of p53 and vascular endothelial growth factor (VEGF) on the liver metastasis in 155 patients with colorectal cancer. The expression of p53, VEGF, and microvessel density (MVD) were immunohistochemically studied. There were significant differences between patients positive for p53 and patients negative for p53, between patients positive for VEGF and patients negative for VEGF, with respect to the occurrence of liver metastases. The frequency of patients positive for both p53 and VEGF in the liver metastases group was significantly higher than that in the control group. The frequency of patients positive for both p53 and v, both VEGF and v in the liver metastases group, was significantly higher than in the control group. MVD in patients positive for VEGF was significantly higher than that negative for VEGF. Thus, p53 and VEGF expression affects the formation of liver metastases from colorectal cancer by the activation of neovascularization followed by feasibility of the extravasation of tumor cells in the tumor tissue.

Colorectal Neoplasms↗
PubMed1998

[Clinicopathological significance of p53 overexpression in elderly patients with colorectal cancer].

The purpose of this study was to elucidate the clinicopathological significance of p53 overexpression in elderly patients with colorectal cancer. p53 positivity for elderly patients and control was 41% and 57%, respectively. There was a significant difference between these two groups. Regarding the rate of hematogenic metastases, there was no significant difference between patients with positive for p53 and negative for p53 in the elderly group (44% vs 39%), on the other hand, there was a significant difference between patients with positive for p53 and negative for p53 in the control group (70% vs 48%). Regarding prognosis, there was no significant difference between patients with positive for p53 and negative for p53 in the elderly group (73.3% vs 72%), on the other hand, there was a significant difference between patients with positive for p53 and negative for p53 in the control group (51.2% vs 68.7%). These results suggest that the significance of p53 overexpression was negligible in elderly patients with colorectal cancer.

Adult↗
PubMed1997

Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells.

In this report, we establish a regulatory role of natural killer (NK) cells in experimental autoimmune encephalomyelitis (EAE), a prototype T helper cell type 1 (Th1)-mediated disease. Active sensitization of C57BL/6 (B6) mice with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide induces a mild form of monophasic EAE. When mice were deprived of NK cells by antibody treatment before immunization, they developed a more serious form of EAE associated with relapse. Aggravation of EAE by NK cell deletion was also seen in beta 2-microglobulin-/- (beta 2m-/-) mice, indicating that NK cells can play a regulatory role in a manner independent of CD8+ T cells or NK1.1+ T cells (NK-T cells). The disease enhancement was associated with augmentation of T cell proliferation and production of Th1 cytokines in response to MOG35-55. EAE passively induced by the MOG35-55-specific T cell line was also enhanced by NK cell deletion in B6, beta 2m-/-, and recombination activation gene 2 (RAG-2)-/- mice, indicating that the regulation by NK cells can be independent of T, B, or NK-T cells. We further showed that NK cells inhibit T cell proliferation triggered by antigen or cytokine stimulation. Taken together, we conclude that NK cells are an important regulator for EAE in both induction and effector phases.

Amino Acid Sequence↗
PubMed1997

Cathepsin K antisense oligodeoxynucleotide inhibits osteoclastic bone resorption.

Cathepsin K is a recently identified cysteine protease which is abundantly and selectively expressed in osteoclasts. To evaluate the contribution of cathepsin K to bone resorption processes, we investigated the effect of cathepsin K antisense phosphothiorate oligodeoxynucleotide (S-ODN) on the bone-resorbing activity of osteoclasts. Rabbit osteoclasts were cultured on dentine slices for 24 h in the presence or absence of antisense S-ODN in a medium containing 100 nM TfxTM-50, polycationic liposome, as a carrier of the S-ODN. Uptake of the S-ODN by osteoclasts was confirmed microscopically using fluorescein-labeled S-ODN. The treatment with antisense significantly decreased the amount of cathepsin K protein in osteoclasts. The antisense inhibited the osteoclastic pit formation in a concentration-dependent fashion. At 10 microM the antisense reduced the total pit number and area and average pit depth by 46, 52, and 30%, respectively. The sense and mismatch S-ODNs, which were used as negative controls, had no effect on either the cathepsin K protein level or the pit formation. A nonspecific cysteine protease inhibitor, E-64, also reduced pit formation in a concentration-dependent manner with maximum reductions at 1 microM of 46, 48, and 35% in the above pit parameters. The inhibitory effect of the antisense almost equal to that of E-64 demonstrates that cathepsin K is a cysteine protease playing a crucial role in osteoclastic bone resorption.

Animals↗
PubMed1997

Results of preoperative intraluminal brachytherapy combined with radical surgery for middle and lower rectal carcinomas.

BACKGROUND: Radiation therapy in the treatment of rectal carcinoma has received attention. We attempted to learn whether preoperative intraluminal brachytherapy (IBT) gives an advantage in local control and/or prolongation of survival. METHODS: One hundred and fifteen patients with middle and lower rectal carcinoma with penetration into or through the rectal wall were consecutively treated with preoperative IBT and radical operation. Patients were divided into the moderate-dose group (group A: 16-40 Gy; n = 96) and the high-dose group (group B: 40-80 Gy; n = 19). A control group of 115 rectal carcinoma patients who received no radiation prior to radical surgery was compared (group C). RESULTS: The rate of sphincter-saving resection was 72% in group A, 63% in group B, and 42% in group C (group A vs. group C; P < 0.0001). The local recurrence rate at 5 years was 11% in group A, 6% in group B, and 26% in group C (group A vs. group C; P = 0.005). The 5-year survival rate was similar among the three groups. CONCLUSIONS: These results suggested that IBT contributed to the improvement of local control but not survival after radical resection of rectal carcinomas. The application of IBT might be useful in preserving the intestinal continuity for rectal carcinomas.

Adult↗
PubMed1997

Nitric oxide-related neural components in the rat small intestine after transplantation.

The changes in nitric oxide (NO)-related neural components in the transplanted small intestine are unknown. In this study, the NO neural component was examined using electrophysiological and NADPH-diaphorase histochemical techniques in a rat small bowel transplantation model. Syngeneic total small bowel transplantation was performed in 26 male Lewis rats using microsurgical techniques. The rats were divided into four groups: an untreated control group and animals at 1 (G1), 2 (G2), and 4 (G4) weeks after transplantation. Jejunal strips were mounted in a superfusion apparatus for examination. In the presence of atropine and guanethidine, the effect of the NO synthesis inhibitor L-NG-nitro-arginine (L-NNA, 100 microM) relaxation mediated by the nonadrenergic, noncholinergic (NANC) neural system was assessed following electrical stimulation at 2Hz. The inhibitory effect of L-NNA on relaxation was taken as an indicator of NO production. The percentage of inhibition in the control group, and in G1, G2, and G4 was 43.30% +/- 6.08% (mean +/- SE), 42.10% +/- 6.69%, 43.62 +/- 10.00%, and 52.46% +/- 6.00%, respectively. Inhibition in G4 was significantly higher than in the other groups (P < 0.01). The percentage of NADPH-diaphorase-positive fibers in the control group, G1, G2, and G4 was 25.06% +/- 4.70% (mean +/- SE), 26.27% +/- 2.17%, 24.73% +/- 2.87%, and 30.76% +/- 3.19%, respectively. Again, G4 showed a significantly higher level than the other groups (P < 0.01). We conclude that increased NO production may play a significant role in maintaining the intrinsic nervous system of the small intestine after transplantation.

Animals↗
PubMed1997

Multivariate analysis of the prognostic factors of patients with unresectable synchronous liver metastases from colorectal cancer.

PURPOSE: It frequently is observed that widely varying prognoses are given for patients with the same extent of liver metastases from colorectal cancer, even though the same treatment is performed on these patients. One of the reasons for this variance is that prognostic factors for these patients have not been defined. This study was designed to elucidate which clinicopathologic factors were the most important in the prognosis of 73 patients with unresectable synchronous liver metastasis from colorectal cancer. METHODS: Univariate and multivariate analysis of 11 clinicopathologic factors were performed using the Cox proportional hazard model. Survival curves were generated using the Kaplan-Meier method. RESULTS: Extent of liver metastases was the most significant variable in this survival analysis, although the extent of lymph node metastases of the primary lesion also was significant. However, the method of treatment was not a significant determinant in the survival for patients with unresectable liver metastases. Median survival of patients with H1, H2, and H3 was 13, 12, and 6 months, respectively, and there was a significant difference between survival curves for patients with H1 and patients with H3. Median survival of patients with n0, n1, and n2 was 13, 7, and 7 months respectively, and there was a significant difference between survival curves for patients with n0 and patients with n2. Median survival of 6 patients with H1 and n0 and of 17 patients with H3 and n2 was 28 and 4 months, respectively. There was a significant difference in survival curves between these two groups. CONCLUSION: Longevity of patients with unresectable synchronous liver metastases from colorectal cancer is affected adversely by the presence of nodal metastases and extent of liver metastases. This should be considered in the planning treatment.

Adult↗
PubMed1997

Functional results after "high" coloanal anastomosis and "low" coloanal anastomosis with a colonic J-pouch for rectal carcinoma.

The aim of this study was to determine the postoperative function of neorectoanal components using two different types of very low coloanal reconstruction. The two groups of patients assessed were 22 who underwent abdominal rectal resection and stapled "high" coloanal anastomosis without a pouch, being the HCAA-P group; and 34 who underwent anoabdominal rectal resection and "low" coloanal anastomosis with a colonic J-pouch, being the LCAA + P group. Manometric examination was performed 1, 3, 6, and 12 months postoperatively, and the patients were also assessed by a questionnaire. The LCAA + P group had remarkably less daily stool frequency and urgency, but there were no significant differences in the other functional parameters. Maximum resting pressure (MRP) was significantly less, while threshold volume (TV) and maximum tolerable volume (MTV) were greater in the LCAA + P group than in the HCAA-P group. The colonic J-pouch compensated for decreased MRP. Thus, when HCAA-P is performed, 3.0 cm of residual rectum with internal anal sphincter may be required, and construction of the pelvic pouch is desirable in low coloanal anastomosis.

Adult↗
PubMed1997

Stapled fistulectomy to treat enteroenteric fistulas in Crohn's disease.

We report herein our technique of performing stapled fistulectomy as minimum surgery for the resection of nine entero-enteric fistulas in six patients with Crohn's disease. The surgical outcome was successful in all patients. It would seem that fistulous sites without a severe affected lesion are a favorable indication for this procedure and we recommend this simplified fistulectomy for selected conditions in Crohn's disease.

Adult↗
PubMed1997

Early expression of proteolipid protein in human fetal and infantile cerebri.

Proteolipid protein (PLP) is the major myelin protein of the central nervous system and is widely believed to play an important structural role in maintaining the myelin compaction. We have studied the early developmental changes of PLP with immunohistochemical methods. Our data demonstrate for the first time a comparable scheme for the development of PLP during myelination in human fetal and infant cerebrum. Expression of PLP was first detected in the pallidothalamic fibers and globus pallidus at 20 weeks; it then extended to the striatum at 28 weeks, pericentral gyri and optic radiation at 35 weeks, and acoustic radiation at 40 weeks. Compared to the expression of myelin basic protein (MBP), another major myelin protein in the central nervous system, the developmental changes of PLP is in the same order as MBP, but the PLP immunoreactivity revealed greater and earlier appearance in the cerebrum than that of MBP in the fetal period. These results imply that PLP is a sensitive and useful marker for early myelination and its disorders.

Brain↗
PubMed1997

Pharmacological characterization of endothelin-induced rat pulmonary arterial dilatation.

1. The aim of study was to characterize endothelin (ET)-induced vasodilation in isolated extrapulmonary rat arteries (EPA) and in intrapulmonary arteries (IPA) preconstricted with 1 microM phenylephrine. 2. The ET-3 (1 nM-100 nM)- and ET-1 (10 nM-100 nM)-induced transient vasodilatations in EPA were more potent than those in IPA. The vasodilatation induced by ET-3 (100 nM) was larger than that induced by ET-1 (100 nM). 3. Both the ETB antagonist, BQ788 (3 microM) and or endothelium denudation, but not the ETA antagonist, BQ123 (3 microM), abolished the vasodilation induced by ET-1 or ET-3 (100 nM each) in EPA and in IPA. The ATP-sensitive K + channel blocker, glibenclamide (20 microM) and the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 1 mM) suppressed the ET-induced vasodilatation in EPA and in IPA. 4. We conclude that the vasodilatation induced by endothelins is markedly reduced in rat isolated IPA, and suggest that the endothelial ETB-mediated vasodilatation varies depending on rat pulmonary arterial regions. Furthermore, ETB-mediated vasodilatation involves activation of ATP-sensitive K+ channels and of nitric oxide synthase in rat isolated EPA and IPA.

Animals↗
PubMed1997

Phagocytic degradation of chylomicron remnants by fibroblasts from subjects with homozygous familial hypercholesterolaemia.

1. Familial hypercholesterolaemia is a common genetic abnormality in man characterized by premature atherogenesis as a consequence of disturbed lipoprotein metabolism. Chylomicrons, which represent intestinally derived lipoproteins, are cleared poorly in familial hypercholesterolaemia which may explain the increased retention of chylomicron remnants in arterial fatty lesions. However, cellular uptake of chylomicron remnants in familial hypercholesterolaemia remains unclear. This study determined the quantitative significance of non-low-density lipoprotein receptor-mediated uptake in fibroblasts from subjects with homozygous familial hypercholesterolaemia. 2. The metabolism of chylomicron remnants was assessed in fibroblasts from subjects with homozygous familial hypercholesterolaemia who lack low-density lipoprotein receptors. Compared with fibroblasts from normolipidaemic subjects, binding and degradation of chylomicron remnants was reduced by about two-thirds. Nevertheless, degradation of chylomicron remnants in cells from subjects with familial hypercholesterolaemia persisted in the absence of functioning low-density lipoprotein receptors. 3. Binding of chylomicron remnants to fibroblasts from subjects with familial hypercholesterolaemia was saturable. Unlabelled chylomicron remnants competed efficiently for binding but unlabelled low-density lipoprotein or a monoclonal antibody specific to the human low-density lipoprotein receptor had little effect on binding or degradation. 4. Polyinosinic acid did not alter binding and degradation of chylomicron remnants by fibroblasts from subjects with familial hypercholesterolaemia, ruling out involvement of the scavenger receptor. Lactoferrin was found to inhibit binding and degradation of chylomicron remnants by fibroblasts from subjects with familial hypercholesterolaemia by approximately 50%, implicating involvement of the alpha 2-macroglobulin receptor. 5. Cytochalasin D blocked degradation of chylomicron remnants at 37 degrees C in fibroblasts from subjects with familial hypercholesterolaemia by more than 80% but had no effect on binding at 4 degrees C, consistent with a phagocytic uptake pathway. Collectively, the data suggest that chylomicron remnants bind to a cell-surface protein which initiates phagocytosis and that lactoferrin interferes with binding to this putative cell-surface protein. Phagocytic uptake of chylomicron remnants provides an additional mechanism whereby cells from subjects with familial hypercholesterolaemia can accumulate lipid.

Adult↗
PubMed1997

Pharmacological heterogeneity of constrictions mediated by endothelin receptors in rat pulmonary arteries.

The endothelin (ET) receptors mediating rat pulmonary arterial constrictions were investigated. ET-1 and ET-3 constricted both isolated intrapulmonary artery (IPA) and extrapulmonary artery (EPA), with ET-1 having a potency approximately 10 times that of ET-3. The ET(B) selective agonist IRL-1620 produced constriction of only IPA. The ET(B) selective antagonist BQ-788 suppressed the ET-1-induced constriction of IPA only. The ET(A) selective antagonist BQ-123 more effectively antagonized the ET-1-induced constriction of EPA than that of IPA. The combination of BQ-123 and BQ-788 increased the antagonistic response to ET-1 in IPA but not in EPA. Then, large constriction remained in IPA and EPA. The receptor nonselective antagonist PD-145065 almost completely inhibited the ET-1-induced constriction of IPA and EPA. BQ-123 completely inhibited the ET-3-induced constriction of EPA; however, it partially suppressed that of IPA. The combination of BQ-123 and BQ-788 completely inhibited the ET-3-induced constriction of IPA. These results demonstrate that the ET-1-induced constrictions are mediated by both ET(A) and ET(B) in IPA and by ET(A) in EPA. Because of differences in sensitivity to ET receptor antagonists for ET-1- and ET-3-induced constrictions, pharmacological heterogeneity of ET(A) is suggested. Additionally, endothelial denudation affected the ET-3-induced constriction of EPA, but not of IPA, and it didn't affect the response to ET-1. This suggests that the vasodilatory effect of endothelium on ET-3-induced vasoconstrictions varies depending on pulmonary vascular regions.

Animals↗
PubMed1997

Effects of neuropeptides on smooth muscle contraction after small bowel transplantation.

We have previously shown that increased intestinal contraction after small bowel transplantation was associated with marked enhancement in the nonadrenergic, noncholinergic (NANC) intrinsic neural component. In the present study, we examined the effect of three NANC neurotransmitters (substance P, neurotensin, and cholecystokinin-octapeptide, CCK-OP) on jejunal longitudinal muscle strips after syngeneic total small bowel transplantation in rats. Fourteen rats were divided into a normal control group (n = 7) and a group tested 4 weeks after transplantation (n = 7). A superfusion system was used to evaluate the in vitro effects of the three neuropeptides in the presence of atropine and guanethidine. In the control group, maximum contractile response to substance P, neurotensin, and CCK-OP was 5.16 +/- 0.30, 1.46 +/- 0.15, and 1.13 +/- 0.17 mg tension/mg wet weight, respectively, while the values for the transplanted group were 5.71 +/- 0.29, 2.52 +/- 0.17, and 1.20 +/- 0.18 mg tension/mg wet weight. These results show that neurotensin-induced contraction increased significantly after transplantation, but substance P appeared to be the dominant NANC neurotransmitter in both normal and transplanted small bowel.

Animals↗
PubMed1997

[Acute toxicity studies of taltirelin tetrahydrate in mice, rats, and dogs].

The acute toxicity studies of taltirelin tetrahydrate (TA-0910), a new thyrotropin-releasing hormone (TRH) analogue, were performed in Slc:ddY mice, Slc:Wistar rats and beagle dogs of both sexes. The drug was administered to mice and rats by oral (p.o.), intravenous (i.v.) and subcutaneous (s.c.) routes, and to dogs by the p.o. and i.v. routes. LD50 values were more than 5,000 mg/kg in mice and rats of both sexes by the p.o. and s.c. routes. Some mice and rats died immediately after i.v. injection, the LD50 values were more than 2,000 mg/kg in mice of both sexes and calculated as 799 and 946 mg/kg in male and female rats, respectively. The minimum lethal doses were more than 2000 mg/kg in dogs of both sexes by the p.o. route. Though all dogs treated intravenously with 1000 mg/kg could survive during the observation period, a female dog with 500 mg/kg died on the day after administration. In general condition, hyperactivity, tremor and straub tail, that reflected central stimulatory effects of TA-0910, were observed in mice and rats, and also wet dog shaking in only rats. Vomiting and hyperactivity were seen in dogs by the p.o. route, and exaltation (during the dosing) and sedation by the i.v. route. In addition, salivation and transient tachycardia were observed in the both routes. In blood chemical examination, the transient changes of glucose, protein, lipid and/or serum enzyme were shown. In autopsy, no notable changes were seen in mice, rats and dogs.

Administration, Oral↗
PubMed1997

Oncogenicity studies of taltirelin tetrahydrate (TA-0910) by oral (GAVAGE) administration in CD-1 mice and CD rats.

Oncogenicity studies of taltirelin tetrahydrate (TA-0910), a new thyrotropin-releasing hormone (TRH) analogue, were carried out on CD-1 mice and CD rats. Groups of 60 male and 60 female CD-1 mice received TA-0910, by oral gavage, at dosages of 5, 15 or 50 mg/kg/day. Treatment continued for a minimum period of 104 weeks. Groups of 55 male and 55 female CD rats received TA-0910, by oral gavage, at dosages of 20, 60 or 200 mg/kg/day. Treatment continued for a minimum period of 90 or 94 weeks for males and females, respectively. Of the treatment-related behavioral changes noted, the majority were considered to be directly related to the known pharmacological activity of the test substance and, as such, to be of questionable direct toxicological significance. In mice, there was no evidence of a treatment-related effect on the incidence of neoplasms. In rats, slightly higher incidences of pituitary adenoma, in males given 60 or 200 mg/kg/day, and thyroid follicular adenoma, in females given 200 mg/kg/day, were noted. However, in neither case was statistical significance attained in pair-wise comparisons, and the incidences were within expectation from background data. There was no evidence of any oncogenic potential of TA-0910 in these studies.

Adenoma↗
PubMed1997

[TCR peptide vaccination for autoimmune diseases: involvement of T-T interaction between autoimmune T cells presenting TCR peptide and CD4-CD8- regulatory T cells].

TCR peptide vaccination has been recently regarded as a future therapy for autoimmune diseases. In spite of the potential value, its underlying mechanisms have not been clearly established. M. F. Kozovska, T. Tabira and I have recently analyzed the immune regulation triggered by V beta 17a-50-68 peptide vaccine in SJL/J mice and desciribed a novel T-T interaction between encephalitogenic T cells presenting TCR peptide and CD4-CD8- regulatory T cells (Journal of Immunology 157:1781, 1996). In this brief review, I discuss how anti-idiotypic regulation can be triggered by the exogenous TCR peptide, and what we have learned from the animal experiments with regard to the natural regulation in human autoimmune diseases such as multiple sclerosis.

Animals↗