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Biomedical subjects

Y Tsuji

Publications and source records attributed to Y Tsuji.

At least 91 records · Page 5Linked to original sources

Transcriptional regulation of the mouse ferritin H gene. Involvement of p300/CBP adaptor proteins in FER-1 enhancer activity.

We previously identified a major enhancer of the mouse ferritin H gene (FER-1) that is central to repression of the ferritin H gene by the adenovirus E1A oncogene (Tsuji, Y., Akebi, N., Lam, T. K., Nakabeppu, Y., Torti, S. V., and Torti, F. M. (1995) Mol. Cell. Biol. 15, 5152-5164). To dissect the molecular mechanism of transcriptional regulation of ferritin H, E1A mutants were tested for their ability to repress FER-1 enhancer activity using cotransfection with ferritin H-chloramphenicol acetyltransferase (CAT) reporter constructs. Here we report that p300/CBP transcriptional adaptor proteins are involved in the regulation of ferritin H transcription through the FER-1 enhancer element. Thus, E1A mutants that failed to bind p300/CBP lost the ability to repress FER-1, whereas mutants of E1A that abrogated its interaction with Rb, p107, or p130 were fully functional in transcriptional repression. Transfection with E1A did not affect endogenous p300/CBP levels, suggesting that repression of FER-1 by E1A is not due to repression of p300/CBP synthesis, but to E1A and p300/CBP interaction. In addition, we have demonstrated that transfection of a p300 expression plasmid significantly activated ferritin H-CAT containing the FER-1 enhancer, but had a marginal effect on ferritin H-CAT with FER-1 deleted. Furthermore, both wild-type p300 and a p300 mutant that failed to bind E1A but retained an adaptor function restored FER-1 enhancer activity repressed by E1A. Sodium butyrate, an inhibitor of histone deacetylase, mimicked p300/CBP function in activation of ferritin H-CAT and elevation of endogenous ferritin H mRNA, suggesting that the histone acetyltransferase activity of p300/CBP or its associated proteins may contribute to the activation of ferritin H transcription. Recruitment of these broadly active transcriptional adaptor proteins for ferritin H synthesis may represent an important mechanism by which changes in iron metabolism are coordinated with other cellular responses mediated by p300/CBP.

3T3 Cells↗

Laparoscopic adrenalectomy for solitary metachronous adrenal metastasis from lung cancer: report of a case.

We report herein the case of a 69-year-old man who underwent laparoscopic adrenalectomy for a solitary adrenal metastasis 10 months after a left lower lobectomy for T2N1M0 lung cancer. A 30 x 20 mm tumor was found in the left adrenal gland, and dissected using an ultrasonically activated scalpel. Histological examination revealed metastatic squamous cell carcinoma. The patient recovered uneventfully and his condition is now stable 18 months after the second operation, with no evidence of local recurrence or metastatic disease. Although laparoscopic resection for malignant adrenal tumors is still controversial, we consider that laparoscopic adrenalectomy may be an optional treatment for metastatic adrenal tumors, provided the tumor is solitary, small in size, and well-localized. To our knowledge, only 14 cases of laparoscopic adrenalectomy for malignant tumors have been reported to date; however, this is the first case of successful laparoscopic adrenalectomy for a metastasis from lung cancer.

Adrenal Gland Neoplasms↗

Transabdominal inguinal hernioplasty combined with abdominal aortic aneurysm repair.

The number of patients being encountered with abdominal aortic aneurysm (AAA) and inguinal hernia is increasing. We describe herein a technique of performing a concomitant one-stage operation for both disorder. After conventional transperitoneal AAA repair, transabdominal preperitoneal hernia repair is carried out through the same incision using a prosthesis made from the same material as the graft used for AAA. The maneuver is similar to that of laparoscopic hernioplasty. We employed this technique in the treatment of four patients, none of whom developed any complications such as infection or recurrence of the inguinal hernia. Thus, we conclude that this one-stage operation for AAA and inguinal hernia may bring physical and economic benefits to patients who have both diseases concomitantly.

Aged↗

Combined resection of the thoracic esophagus and thoracic descending aorta.

We conducted combined resection of the thoracic esophagus and thoracic descending aorta in 2 patients, one with advanced esophageal cancer with aortic invasion and the other aortoesophageal fistula caused by a false aortic aneurysm. Combined resection of esophageal tumor and adjacent involved organs was conducted in 14 patients with A3:T4 esophageal cancer but none survived 3 years and resecting tumor-invaded organs did not improve patient survival. One major problem of combined resection of the esophagus and aorta is contamination of the posterior mediastinum. In 1 patient, 2-stage surgery for the esophagus and in situ aortic replacement was conducted to reduce operative risk and avoiding infection of the prosthetic vascular graft. With thoracic descending aortic aneurysm adjacent to the esophagus on the increase, cardiovascular surgeons should prepared to undertake combined resection of both the aorta and esophagus.

Aged↗

Intraabdominal nonvascular operations combined with abdominal aortic aneurysm repair.

The therapeutic approach to a patient who has an abdominal aortic aneurysm (AAA) and an intraabdominal nonvascular surgical disorder simultaneously remains controversial. To establish guidelines for the management of those patients, a retrospective review of patients who had concomitant AAA and intraabdominal nonvascular surgical disorders was undertaken. During the period January 1988 to December 1997 a series of 162 patients underwent surgical repairs of AAA in our hospital. Among them 16 patients (9.9%) had several kinds of intraabdominal nonvascular surgical disorders, and 13 underwent one-stage operation for both diseases. That is, cholelithiasis coexisted in five patients, inguinal hernia in four, gastric cancer in two, and retroperitoneal tumor and renal tumor in one each. All AAAs were the infrarenal type, and there were no inflammatory or ruptured aneurysms. In cases of cholelithiasis coexistent with AAA, aneurysmectomy was performed first. After tight closure of the retroperitoneum, cholecystectomy was done. In cases of cholelithiasis coexistent with AAA, aneurysmectomy was performed first. After tight closure of the retroperitoneum, cholecystectomy was done. In cases of inguinal hernia coexistent with AAA, the AAA was first replaced with a prosthetic vascular graft and a residual piece of the graft was used as a patch for hernioplasty. This procedure was similar to laparoscopic hernioplasty. In two cases of gastric cancer concomitant with AAA, the AAA was first replaced. Subtotal gastrectomy with D2 lymphatic dissection was done after tight closure of the retroperitoneum. A drain was inserted into the epiploic foramen to detect anastomotic leakage. A retroperitoneal tumor coexisting with AAA was dissected and resected en bloc with the aneurysmal wall because the tumor firmly adhered to the aneurysm. The abdominal aorta was then replaced with a prosthetic graft. In a case of renal tumor concomitant with AAA, nephrectomy was done first to perform a complete lymphatic dissection around the renal artery. Then AAA repair was performed with a conventional procedure. There were no fatal complications, such as pneumonitis, hemorrhage, anastomotic leakage, or graft infection. All 13 patients were discharged from our hospital and are currently free from recurrence of malignancy or hernia. In summary, properly selected one-stage operations for intraabdominal nonvascular surgical disorders and AAA may be safe and bring physical and economic benefit to the patient.

Aged↗

Autosomal dominant onychodystrophy and congenital sensorineural deafness.

The disease "deafness and onychodystrophy" (DOD) is characterized by congenital hearing impairment and dystrophic or absent nails and teeth. The autosomal dominant form of the disorder has been previously reported only in one family. We describe here another family in which three members in three generations (a girl, her mother, and her maternal grandfather) were affected with DOD. Our finding is consistent with an autosomal dominant mode of inheritance and confirms autosomal dominant DOD (DDOD, MIM *124480) as a recognizable clinical entity.

Adult↗

Transaortic video-assisted removal of a left ventricular thrombus.

A mobile and pedunculated left ventricular thrombus was developed after acute myocardial infarction in a 59-year-old man, and was successfully removed surgically through the aortic valve using a video-assisted thoracoscope. Transaortic video-assisted thoracoscopy greatly facilitated exposure of the interior of the left ventricle and preserved left ventricular function by avoiding ventriculotomy.

Endoscopy↗

Heterogeneous distribution of the two components of delayed rectifier K+ current: a potential mechanism of the proarrhythmic effects of methanesulfonanilideclass III agents.

OBJECTIVE: To elucidate the regional difference of the K+ current blocking effects of methanesulfonanilide class III agents. METHODS: Regional differences in action potential duration (APD) and E-4031-sensitive component (IKr) as well as -insensitive component (IKs) of the delayed rectifier K+ current (IK) were investigated in enzymatically isolated myocytes from apical and basal regions of the rabbit left ventricle using the whole-cell clamp technique. RESULTS: At 1 Hz stimulation, APD was significantly longer in the apex than in the base (223.1 +/- 10.6 vs. 182.7 +/- 14.5 ms, p < 0.05); application of 1 microM E-4031 caused more significant APD prolongation in the apex than in the base (32.5 +/- 6.4% vs. 21.0 +/- 8.8%, p < 0.05), resulting in an augmentation of regional dispersion of APD. In response to a 3-s depolarization pulse to +40 mV from a holding potential of -50 mV, both IK tail and IKs tail densities were significantly smaller in apical than in basal myocytes (IK: 1.56 +/- 0.13 vs. 2.09 +/- 0.21 pA/pF, p < 0.05; IKs: 0.40 +/- 0.15 vs. 1.43 +/- 0.23, p < 0.01), whereas IKr tail density was significantly greater in the apex than in the base (1.15 +/- 0.13 vs. 0.66 +/- 0.11 pA/pF, p < 0.01). The ratio of IKs/IKr for the tail current in the apex was significantly smaller than that in the base (0.51 +/- 0.21 vs. 3.09 +/- 0.89; p < 0.05). No statistical difference was observed in the voltage dependence as well as activation and deactivation kinetics of IKr and IKs between the apex and base. Isoproterenol (1 microM) increased the time-dependent outward current of IKs by 111 +/- 8% during the 3-s depolarizing step at +40 mV and its tail current by 120 +/- 9% on repolarization to the holding potential of -50 mV, whereas it did not affect IKr. CONCLUSIONS: The regional differences in IK, in particular differences in its two components may underlie the regional disparity in APD, and that methanesulfonanilide class III antiarrhythmic agents such as E-4031 may cause a greater spatial inhomogeneity of ventricular repolarization, leading to re-entrant arrhythmias.

Action Potentials↗

Production and some properties of salt-tolerant beta-xylosidases from a shoyu koji mold, Aspergillus oryzae in solid and liquid cultures.

Beta-xylosidase production from a shoyu (soy sauce) koji mold, Aspergillus oryzae HL15, cultured in solid and liquid media was examined and some properties of the enzymes were studied. Three beta-xylosidases (Xy11, Xy12 and Xy13) were easily extracted with 0.5% NaCl from a solid medium and purified homogeneously on SDS-PAGE by chromatography. On the other hand, in a liquid medium, A. oryzae HL15 produced mainly cell-wall-bound beta-xylosidases which could not be extracted with 0.5% NaCl or any detergent. Cell-wall-bound beta-xylosidases, Xy11-CB and Xy12-CB, were liberated by digestion of mycelia with Yatalase and purified to a homogeneous state on SDS-PAGE by HPLC column chromatography. Four beta-xylosidases (Xy11, Xy12, Xy11-CB and Xy12-CB) exhibited not only high activity at high NaCl concentrations, but also similar properties; on the other hand, Xy13 differed in terms of thermostability and halophilic properties. The salt tolerance of beta-xylosidases in A. oryzae suggests that these enzymes are highly active and involved in releasing xylose in shoyu moromi mash.

Journal Article↗

Augmentation of immune response by altered peptide ligands of the antigenic peptide in a human CD4+ T-cell clone reacting to TEL/AML1 fusion protein.

The 12;21 chromosomal translocation occurs in leukemic cells from 20(30% of patients with B-lineage childhood acute lymphoblastic leukemia, the result being the TEL/AML1 fusion gene carrying a sequence different from TEL or AML1. Because the protein newly formed by TEL/ AML1 fusion is probably not tolerated by human immune system, the fusion region is a good candidate for tumor antigen expressed only in TEL/ AML1-positive leukemic cells. We established two human CD4+ alphabeta T-cell clones (T31.1 and Y41.2) reacting to the TEL/AML1 fusion region, from two unrelated healthy donors. In order to do this, we stimulated peripheral blood mononuclear cells with synthetic peptides corresponding to the TEL/ AML1 fusion region. Both T31.1 and Y41.2 proliferated in response to TEL/ AML1 fusion protein as well as to a peptide IGRIAECILGMNPSR, in the context of HLA-DP5 and DP17, respectively, and killed B lymphoblastoid cells pulsed with the peptide. Furthermore, these T-cell clones proliferated in response to several altered peptide ligands carrying a single residue substitution in the TEL/AML1 peptide, and some induced augmentation of proliferation and production of Th1-type cytokines. These superagonistic altered peptide ligands can be given consideration for anti-leukemic immunotherapy.

Adjuvants, Immunologic↗

Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase.

The hallmark of type 2 diabetes, the most common metabolic disorder, is a defect in insulin-stimulated glucose transport in peripheral tissues. Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro, its role in vivo and the molecular link between activation of PI3K and translocation has not yet been elucidated. To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). Pik3r1-/- mice showed increased insulin sensitivity and hypoglycaemia due to increased glucose transport in skeletal muscle and adipocytes. Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice. This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) in Pik3r1-/- adipocytes and facilitation of Glut4 translocation from the low-density microsome (LDM) fraction to the plasma membrane (PM). This mechanism seems to be responsible for the phenotype of Pik3r1-/- mice, namely increased glucose transport and hypoglycaemia. Our work provides the first direct evidence that PI3K and its regulatory subunit have a role in glucose homeostasis in vivo.

Animals↗

A comparative study of endoscopic trigonoplasty for vesicoureteral reflux in children and in adults.

BACKGROUND: Endoscopic trigonoplasty is an experimental therapy for vesicoureteral reflux. We investigated differences in surgical results between children and adults. METHODS: Endoscopic trigonoplasty was performed on 51 patients and 15 pediatric and 21 adult patients were included in this study. The children accounted for 27 cases of refluxing ureter (grade II, 8; III, 14; IV, 4; V, 1) and the adults for 28 cases (I, 4; II, 18; III, 4; IV, 2). There was a greater proportion of bilateral disease and a higher average degree of reflux in the children's group. RESULTS: We found no significant differences in operative time, complications, analgesics usage, the duration of the indwelling catheter and hospital stay. Our follow up at 3 months showed that the reflux had ceased in 19 of 27 cases (70%) in the children's group and in 27 of 28 cases (96%) in the adults' group. The next follow up at 12 months showed that there was no reflux in 16 of 27 cases (59%) in 15 children and in 17 of 23 adult cases (74%). Trigonal splitting caused recurrence of reflux greater than grade II, in two children (13%) affecting four ureters and in three adults (14%) affecting four ureters. CONCLUSIONS: Endoscopic trigonoplasty has proved to be equally less invasive in children and in adults, but vesicoureteral reflux was less often resolved in children. This suggests that the greater original distance between the ureteral orifices and the greater thickness of the detrusor muscle favor the adult patient. For children, a new surgical concept is needed to increase cessation rate of vesicoureteral reflux.

Adult↗

Closure of mouth of bladder diverticulum via endoscopic transvesico-transurethral approach.

We successfully treated bladder diverticula in two patients using the endoscopic transvesico-transurethral approach. The mouth of the diverticulum was closed in two layers under pneumobladder, using two percutaneous ports placed into the bladder as well as the urethral route. This operation was performed 2 to 3 months after the bladder outlet obstruction was relieved by transurethral resection or incision of the prostate. The patients were able to void with a minimum of residual urine. The endoscopic transvesico-transurethral approach provided satisfactory vision.

Aged↗

A pilot study of CPT-11 and cisplatin for ovarian clear cell adenocarcinoma.

BACKGROUND: Ovarian clear cell adenocarcinoma is known to have poorer prognosis than ovarian serous cystadenocarcinoma. Cyclophosphamide plus cisplatin has been the standard therapy for ovarian cancer, but ovarian clear cell adenocarcinoma dose not respond to this therapy. The treatment for ovarian clear cell adenocarcinoma has not been established. We planned a pilot study of CPT-11 and cisplatin for the treatment of ovarian clear cell adenocarcinoma. METHODS: First, three patients were administered 70 mg/m2 of cisplatin intravenously on day 1 and 60 mg/m2 of CPT-11 intravenously on days 1, 8 and 15. Treatment was repeated every 4 weeks. Other patients were administered 75 mg/m2 of cisplatin intraperitoneally on day 1 and 60 mg/m2 of CPT-11 intravenously on days 1, 8 and 15. Treatment was repeated every 4 weeks. RESULTS: A total of 10 patients were entered in this study and a total of 43 courses were administered. 1 CR, 1 PR and 1 PD were observed in patients with measurable lesion. Grade 3 leukopenia was experienced in seven patients, grade 3 thrombocytopenia in two and grade 3 anemia in five. Grade 3 liver toxicity was observed in one patient and grade 3 diarrhea in one patient. No grade 4 toxicity was experienced. CONCLUSION: CPT-11 plus cisplatin is feasible and has efficacy for ovarian clear cell adenocarcinoma. This regimen should be explored in a phase II study.

Adenocarcinoma, Clear Cell↗

Peak position of dissipation spectrum in turbulent boundary layers.

The peak locations of energy dissipation spectrum (y(+)(kp)) are investigated experimentally in the low Reynolds number (R(theta)<5000) zero-pressure-gradient turbulent boundary layers. These peaks are scaled by the relation y(+)(kp)=2(u(*)delta/nu)(1/2)=2R(1/2)(*), where u(*) is friction velocity and delta is the boundary layer thickness. They are located close to the peak positions of the Reynolds shear stress (y(+)(p)), that is, y(+)(kp) approximately equal to y(+)(p). This result predicts that the small-scale structures residing in high-energy dissipation regions concentrate around y(+)(p).

Journal Article↗