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T Ouchi

Publications and source records attributed to T Ouchi.

At least 37 records · Page 2Linked to original sources
PubMed1998

BRCA1 regulates p53-dependent gene expression.

Mutations in BRCA1 are present in 45% of families that segregate with susceptibility for breast cancer and in 80-90% of families with both breast and ovarian cancer. Here we report that BRCA1 stimulates artificial and genomic promoter constructs containing p53-responsive elements. This activity of BRCA1 depends on the presence of wild-type p53, which was shown by using mouse fibroblasts expressing temperature-sensitive forms of p53, or p53(+/+) and p53(-/-) fibroblasts obtained from p53 knockout mice. Furthermore, mutant forms of BRCA1 lacking the C-terminal second BRCA1 C-terminal (BRCT) domain showed reduced p53-mediated transcriptional activation. Finally, we found that BRCA1 coimmunoprecipitates with p53, in vitro and in vivo. These findings suggest a function of BRCA1 as a p53 coactivator.

Animals↗
PubMed1998

Heterotopic pancreas of the esophagus associated with a rare type of esophageal atresia.

An infant with a rare type of esophageal/tracheal anomaly associated with heterotopic pancreas of the esophagus is herein reported. The upper pouch containing heterotopic pancreas reached 1.5 cm below the tracheal carina, and the distal esophagus connected to the trachea 2 cm above the tracheal carina and thus formed a partial duplication of the esophagus. Heterotopic pancreas of the esophagus is extremely rare, with only 7 cases previously reported. Here we report the combination of heterotopic pancreas and esophageal atresia with tracheoesophageal fistula.

Anastomosis, Surgical↗
PubMed1998

[Implementing HPN in an SEP case following long-term CAPD].

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is one of the most serious complications in continuous ambulatory peritoneal dialysis (CAPD). SEP causes severe bowel obstruction leading to malnutrition and eventually to a high mortality rate. The basic strategy for the care of SEP is to sustain the rest of the bowel, i.e., long-term TPN. We report a case successfully restored to a useful life through HPN. CASE PRESENTATION: The patient is a 26-year-old man, diagnosed as primary nephrotic syndrome in 1980. He had to begin hemodialysis (HD), which was immediately switched to CAPD, due to uremia in 1983. He had been on CAPD for 12 years since that time. He developed SEP as a serious complication of CAPD in July, 1995. CAPD was discontinued, and maintenance HD was started three times a week. Although only liquid diet (such as Renalen and Ensure-Liquid) was allowed as a meal, he often developed intermittent bowel obstruction and repeated hospitalizations were needed to relieve the symptoms. Home parenteral nutrition (HPN) was implemented in May, 1997, in the hope of improving his quality of life. No hospitalization has been needed since then. At present, he is working as an active pharmacist utilizing the HPN system developed by Terumo Co., Ltd. So far a few HPN pump failures have been encountered, but they were promptly handled by the Home Health Care Business Project staff at Terumo Co., Ltd. CONCLUSION: Although further improvements of the present HPN system are necessary, HPN can be a useful tool to effectively manage SEP patients who are suffering from persistent or intermittent bowel obstruction.

Adult↗
PubMed1997

Downstream of Crk adaptor signaling pathway: activation of Jun kinase by v-Crk through the guanine nucleotide exchange protein C3G.

Crk, which belongs to the adaptor family of proteins composed of Src homology 2 (SH2) and SH3 domains, has a putative role in signaling. However, the downstream events of Crk signaling remain unclear. In this study, we found that Jun kinase (JNK) is moderately activated by v-Crk in both NIH 3T3 cells and chicken embryo fibroblasts. Transient expression of v-Crk, c-Crk-I, or c-Crk-II activated JNK1 in human embryo kidney cells, 293T. Coexpression of a guanine nucleotide exchange protein C3G, which specifically binds to Crk's SH3 domain, further enhanced the JNK activity as well as growth rate and anchorage-independent growth of v-Crk NIH 3T3 cells. Furthermore, overexpression of a dominant-negative form of C3G lacking the guanine nucleotide exchange domain abolished both the JNK activity and the colony forming potential of v-Crk NIH 3T3 cells. The requirement for JNK activation in v-Crk induced transformation was demonstrated by the suppression of colony forming activity of v-Crk NIH 3T3 cells when a dominant-negative form of JNK kinase, Sek1/MKK4 is expressed in these cells. These data strongly suggest the existence of a novel signaling cascade involving an adaptor protein v-Crk, which transmits signals through C3G toward JNK activation.

3T3 Cells↗
PubMed1997

Effect of dimerization of the D-glucose analogue of muramyl dipeptide on stimulation of macrophage-like cells.

N-Acetylmuramyl-L-alanyl-D-isoglutamine (MDP) is the minimum required structure responsible for the immunoadjuvant activity of the bacterial cell wall. The D-glucose analogue of MDP (GADP) was reported to show a higher immunoadjuvant activity than MDP itself. Although the mechanism of activation by MDP and the existence of receptor against MDP are not clear, the patch formation and cluster formation of receptors are important steps on the signal transduction by such bioactive molecules. It is expected that the cluster effect such as antennary oligosaccharides reported by Lee et al. increased the affinity of ligand against receptor and accelerated the patch formation and cluster formation of receptors. In order to discuss the effect of multivalent-ligand formation of GADP on the activation of immunocompetent cells in more detail, we have synthesized GADP dimers combined through various lengths of alkyl and poly(ethylene glycol) (PEG) spacer groups as the simple models of multivalent-ligand molecule of GADP and evaluated their immunological enhancement activities in vitro. The GADP dimers showed a higher level stimulatory activities against macrophage-like cells than free GADP and monomeric GADP derivatives.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

Design of macromolecular biological response modifier by immobilizing of D-glucose analogue of muramyl dipeptide on carboxymethyl-dextran having mannose branches.

It is well known that muramyl dipeptide is a minimum required structure of bacterial peptidoglycan responsible for immunoadjuvant activity. Since mannose receptors exist on the surface of macrophages, polymers with branched mannose residues are expected to target moieties to macrophages. To achieve an efficient delivery of D-glucose analogue of muramyl dipeptide (GADP) via receptor-mediated endocytosis by mannose receptors on the surface of macrophages, GADP/carboxymethyl-dextran (CM-Dex)/Man conjugate was synthesized. Moreover, to study the effect of the introduction of mannose residues, we also synthesized GADP/CM-glucomannan (CM-GM) and GADP/CM-Dex conjugates. The immunological enhancement activities of their conjugates were evaluated by measurements of glucose consumption and beta-D-glucuronidase activity from macrophage-like cells. The GADP/CM-Dex/Man and GADP/CM-GM conjugates showed higher immunological enhancement activity than the GADP/CM-Dex conjugate. The immunological enhancement activity of GADP/CM-Dex/Man and GADP/CM-GM conjugates was decreased to the same level of immunological enhancement activity of GADP/CM-Dex conjugate under the presence of excess mannose. These results suggested that the introduction of mannose residues into GADP/CM-Dex conjugate could increase the affinity against macrophage and the immunological enhancement activity of GADP/CM-Dex conjugate itself.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1996

Synthesis and cytotoxic activity of dextran carrying cis-dichloro(cyclohexane-trans-l-1,2-diamine)platinum(II) complex.

cis-Dichloro(cyclohexane-trans-l-1,2-diamine)platinum(II) (Dach-Pt(chlorato)), is a platinum complex which is expected to exhibit higher antitumor activity than, and show no cross resistance with, cisplatin. However, its strong side-effects and low water-solubility have also been cited. We report that polymer/antitumor drug conjugates shows reduced side-effects and high antitumor activity. In order to provide a macromolecular prodrug of Dach-Pt having reduced side-effects and high water-solubility, we synthesized polymer conjugates of Dach-Pt and dextran derivatives having carboxylic acid groups, oxidized-dextran (OX-Dex)/Dach-Pt conjugate, and carboxymethyl-dextran(CM-Dex)/Dach-Pt conjugate. The cytotoxic activities of the conjugates were investigated against p388D1 lymphocytic leukemia cells in vitro. The OX-Dex/Dach-Pt conjugate showed almost the same level of cytotoxic activity as free Dach-Pt(chlorato). Although the cytotoxic activity of free Dach-Pt(chlorato) was decreased by incubation in medium with serum, the OX-Dex/Dach-Pt conjugate kept its cytotoxic activity in higher level after 24 h incubation in medium with serum. These results suggested that the stability of Dach-Pt molecule in the medium was increased and cytotoxic activity of Dach-Pt was not decreased by fixing to OX-Dex.

Animals↗
PubMed1992

Synthesis and antitumor activity of 6-O-carboxymethyl chitin fixing 5-fluorouracils through pentamethylene, monomethylene spacer groups via amide, ester bonds.

In order to provide the water-soluble and biodegradable macromolecular prodrug of 5-fluorouracil (5FU), the fixation of 5FUs to 6-O-carboxymethyl chitin(CM-chitin) through pentamethylene, monomethylene spacer groups via amide, ester bonds was carried out. The obtained CM-chitin/5FU conjugate showed the slow release of 5FU and exhibited remarkable antitumor activity against P388 lymphocytic leukemia in mice by intraperitoneal(i.p.) implantation/i.p. injection.

Animals↗
PubMed1992

Synthesis and antitumor activity of poly(ethylene glycol)s linked to 5-fluorouracil via a urethane or urea bond.

In order to provide a macromolecular prodrug of 5-fluorouracil (5FU) with reduced side-effects and exhibiting strong antitumor activity, 5FU was covalently linked to poly(ethylene glycol) (PEG) via a urethane or urea bond. For the purpose of evaluating the release behavior of 5FU, the hydrolysis of the urethane or urea bond in the obtained conjugate of PEG-end capped with 5FU was investigated in vitro at 37 degrees C in aqueous solution media. The survival effect for the conjugate was assessed in vivo against p388 lymphocytic leukemia in female CDF1 mice by intraperitoneal (i.p.) transplantation/i.p. injection. The effects of a hydrophobic hexamethylene spacer group, the end group and the number n of ethylene oxide (EO) units in PEG on the release behavior of 5FU and the survival effect were investigated. The release rate of 5FU from the 5FU-terminated PEG conjugates via urethane or urea bond was very fast. However, it became slow with increasing n of EO units in PEG and was depressed by the introduction of hydrophobic spacer group. The 5FU-terminated PEG conjugates obtained exhibited significant survival effects against p388 leukemia mice i.p./i.p. Especially, the methoxy PEG (n = 113)/urethane/hexamethylene/urea/5FU conjugate showed the strongest survival effect among the synthesized 5FU-capped PEG conjugates via urethane or urea bond compared to free 5FU against p388 leukemia mice. These conjugates obtained did not display an acute toxicity even in high dose ranges.

Animals↗
PubMed1990

Synthesis and antitumor activity of conjugates of 5-fluorouracil and chito-oligosaccharides involving a hexamethylene spacer group and carbamoyl bonds.

With the object of providing an oligomeric prodrug of 5-fluorouracil (5FU) with reduced side-effects, affinity for tumor cells and high antitumor activity, 5FU was covalently attached to three chito-oligosaccharides (COS) through hexamethylene spacer groups via carbamoyl bonds. The ability of these conjugates to prolong the life of lymphocytic leukemia mice (following their intraperitoneal administration) and their tumor-inhibitory effects on Meth-A fibrosarcoma or MH-134 hepatoma mice (following their subcutaneous administration) were assessed. The conjugates caused a significant increase in the survival time of the p-388 leukemia mice, and higher growth-inhibitory effects against the solid tumor than either 5FU, COS, or blends of 5FU and COS. At the highest dose levels, the conjugates did not cause acute toxicity, and did not cause rapid decrease in body weight.

Animals↗
PubMed1989

[Clinical application of Sonolith 2000 type B on extracorporeal shock wave lithotripsy for upper urinary tract calculi].

This report describes the results of clinical trials of the second generation extracorporeal shock wave lithotriptor (Sonolith 2000 Type B) in patients with upper urinary tract stones. The studies were carried out on 101 cases at the Departments of Urology, Juntendo University School of Medicine, Kanto Teishin Hospital and General Daiyukai Hospital from Nov. 1987 to Jun. 1988. The location of stones were renal calyx and pelvis in 84 cases, ureteropelvic junction in 7 cases and upper ureter in 12 cases (2 of them had multiple stones at different levels). The average number of treatment per a patient was 1.25, and that of shock waves delivered per treatment was 1798. Ultrasound localization has been effective in all cases. The rate of destruction of the stones was 100% in the kidney, 66.7% in the upper ureter, with an overall average of 95.0%. On the X-ray film obtained six weeks after ESWL treatment, the stone free rate was 53.5%, and the effectiveness rate was 89.1%, including the cases of stone free and cases with fragments smaller than 5 mm. No serious adverse effect was observed, although there were mild transient hematuria in all cases and pyrexia (more than 38.0 degrees C) in 7 cases (6.9%). The procedure was performed safely in the majority of patients without anesthesia. In 10 cases, we applied anesthesia (epidural anesthesia in 3 cases, and local anesthesia in 7 cases) for the prevention of pain. It is concluded that ESWL treatment using Sonolith 2000 Type B is as effective as other types of shock wave lithotriptor previously applied to urolithiasis without serious clinical complication.

Adult↗
PubMed1987

[High-risk group--colorectal cancer].

The environmental factor, pathogenic factor, host factor and others can be assumed as high-risk factors of colon carcinoma. Histopathologically, in most cases, colon carcinoma is recognized as an adenoma-carcinoma sequence that originates based on the adenoma. In this study, in addition to the adenoma and adenomatosis (familial polyposis, Gardner syndrome, Turcot syndrome), the hamartoma (Peutz-Jeghers syndrome, juvenile polyp), inflammatory bowel diseases (ulcerative colitis, Crohn's disease, fistel ani and others) and the origin of the carcinoma were examined. The oncogenesis based on the tubular adenoma, tubulovillous adenoma, villous adenoma and genetic adenomatosis of the large intestine could be found in many cases, thereby requiring a wide range of examinations and treatments. Concerning the oncogenesis of several kinds of inflammatory bowel diseases, much attention should be paid to diseases such as ulcerative colitis, Crohn's diseases, and fistel ani extending over a period of 10 years. In addition, it is necessary to study the connection and promotion among factors of the environmental, pathogenic and host factors.

Adenomatous Polyposis Coli↗
PubMed1985

NMR imaging of congenital intracranial germinal layer neoplasms.

NMR images in five patients with surgically proved, congenital germinal layer intracranial neoplasms (two dermoid and three epidermoid tumors) were reviewed. The dermoids were typically midline (suprasellar or parapineal) masses with sharply-defined margins. Relaxation times were variable, but if fat was present, T1 was decreased, and T2 was increased. The epidermoids were off the midline (cerebellopontine angle, temporal lobe, frontal lobe) masses with generally long T1 and T2 relaxation times. Obstructive hydrocephaly was noted in one patient, and tumor to ventricular communication was demonstrated in another.

Adolescent↗
PubMed1984

[Effect of radiotherapy against advanced carcinoma of the rectum].

In treating advanced carcinoma of the rectum, we have actively used radiotherapy as an adjunct to surgery to enlarge the group of patients indicating surgery and improve the remote results. Of total 423 patients with rectal cancer treated by us in the past 16 years, 202 patients (47.8%) received radiotherapy. Preoperative radiotherapy was performed on 90 of these patients, postoperative radiotherapy on 73 patients, preoperative plus postoperative radiotherapy on 15 patients, and radiotherapy alone on 24 patients. The present study is mainly concerned with preoperative radiotherapy. The purpose of preoperative radiotherapy is to increase the number of patients suitable for surgery. We selected Dukes-C cases without distant metastasis as indications for preoperative radiotherapy, and treated them by 2-step irradiation with 3,000-6,000 rads using Linac after 2 weeks of preoperative observation. The gross and histologic evaluation of the results of irradiation permitted us to conclude that over 3,000 rads was necessary for preoperative radiotherapy. Comparison of the results between preoperative radiotherapy and control groups showed that local recurrence occurred in 6.7% of the radiotherapy group and 9.0% of the control, and 5-year-survival rate was 62.7% and 53.2% respectively, with prognosis improved in the radiotherapy group.

Combined Modality Therapy↗