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T Sakaguchi

Publications and source records attributed to T Sakaguchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Expression of zebrafish btg-b, an anti-proliferative cofactor, during early embryogenesis.

BTG/tob family proteins are thought to be a potential tumor suppressor due to their anti-proliferative activity. We cloned zebrafish btg-b, a member of the BTG1/2 subfamily, using in situ hybridization screening. The tissue-specific expression of btg-b is first observed in the organizer region at the early gastrula stage. Later in development, the forebrain, the hindbrain, the polster and the paraxial mesoderm transiently express btg-b. Recently, mouse Btg1 and Btg2 have been shown to be a cofactor for Hoxb9. Double in situ hybridization with zebrafish btg-b and hoxb9a indicates that the expression domains of these two genes overlap in the posterior paraxial mesoderm.

Amino Acid Sequence↗
PubMed2001

A novel sox gene, 226D7, acts downstream of Nodal signaling to specify endoderm precursors in zebrafish.

Vertebrate endoderm development has recently become the focus of intense investigation. We have identified a novel sox gene, 226D7, which is important in zebrafish endoderm development. 226D7 was isolated by an in situ hybridization screening for genes expressed in the yolk syncytial layer (YSL) at the blastula stage. 226D7 is expressed mainly in the YSL at this stage and, during gastrulation, its expression is also detected in the forerunner cells and endodermal precursor cells. The expression of 226D7 is positively regulated by Nodal signaling. The knockdown of 226D7 using morpholino antisense oligonucleotides results in a lack of sox17-expressing endodermal precursor cells during gastrulation, and, consequently, lacks endodermal derivatives such as gut tissue. The effect is strictly restricted to the endodermal lineage, while the mesoderm is normally formed, a phenotype that is nearly identical to that of the casanova mutant (Dev. Biol. 215 (1999) 343). We further demonstrate that overexpression of 226D7 increases the number of sox17-expressing endodermal progenitor cells without upregulating the expression of the Nodal genes, cyclops and squint. Region-specific knockdown and overexpression of 226D7 by injection into the YSL suggest that 226D7 in the YSL is not involved in endoderm formation and 226D7 in the endoderm progenitor cells is important for endoderm development. Taken together, our data demonstrate that 226D7 is a downstream target of Nodal signal and a critical transcriptional regulator of early endoderm formation.

Amino Acid Sequence↗
PubMed2001

Clinical application of vacuum-assisted cardiopulmonary bypass with a pressure relief valve.

OBJECTIVES: Hemodilution induced by cardiopulmonary bypass (CPB) often prevents open heart operations without blood transfusion because of a large CPB-priming volume. A vacuum-assisted venous drainage system appears to overcome this problem and our previous experimental study demonstrated the beneficial effect of a vacuum-assisted CPB with a pressure relief valve. In this study, we clinically applied this novel system, and evaluated its efficacy by comparing it with the results of a conventional siphon-dependent drainage system. METHODS: Sixty patients undergoing open heart operation were divided into Group V (vacuum-assisted system, n=30) and Group S (siphon-dependent system, n=30). The vacuum-assisted system contains a powerful vacuum generator and a pressure relief valve to keep the negative pressure in the reservoir constant when the blood suction is used. RESULTS: The CPB-priming volume was significantly smaller in Group V (V vs. S: 1071+/-88 vs. 1405+/-137 ml; P<0.01), resulting in the lower hemodilution in Group V evidenced by the minimum hemoglobin level (V vs. S: 6.83+/-1.06 vs. 5.78+/-0.79 mg/dl; P<0.01) and blood transfusion rate (V vs. S: 9 vs. 20%; P<0.01). There were no significant differences in the plasma free hemoglobin level and the reduction ratio of plasma haptoglobin between the groups. CONCLUSIONS: These data demonstrate that this vacuum-assisted CPB can provide simplification of the CPB circuit, resulting in a smaller CPB-priming volume and lower hemodilution. This vacuum-assisted CPB may attenuate the negative effect of CPB by minimizing hemodilution and appears to be a useful modification to accomplish no blood-requiring open heart operations.

Blood Transfusion↗
PubMed2001

Measurements of LET-distribution, dose equivalent and quality factor with the RRMD-III on the Space Shuttle Missions STS-84, -89 and -91.

Dosimetric measurements on the Space Shuttle Missions STS-84, -89 and -91 have been made by the real-time radiation monitoring device III (RRMD-III). Simultaneously, another dosimetry measurement was made by the Dosimetry Telescope (DOSTEL) on STS-84 and by the tissue-equivalent proportional counter (TEPC) on STS-91. First, the RRMD-III instrument is described in detail and its results summarized. Then, the results of DOSTEL and TEPC are compared with those of the RRMD-III. Also, the absorbed doses obtained by TLD (Mg2SiO4) and by RRMD-III on board STS-84 and -91 are compared.

Atlantic Ocean↗
PubMed2001

Conserved and non-conserved regions in the Sendai virus genome: evolution of a gene possessing overlapping reading frames.

We have sequenced the entire genome of a virulent field isolate of Sendai virus, the Hamamatsu strain, and compared the sequence with that of a distant related strain, the Z strain. Calculation of synonymous and non-synonymous (amino acid changing) nucleotide substitutions revealed regions where changes were permissive and non-permissive, and the experimentally determined functional region were found to be conserved, showing that important regions for function were conserved during evolution. In the cistron-overlapping regions in the P gene, one reading frame was conserved, whereas the other overlapping frame was flexible. The priority of one frame could be a strategy for evolution of an overlapping gene of RNA viruses. We found that the carboxyl two thirds of the C protein was conserved over the amino-terminal one third, possessing priority to the overlapping P polypeptide. This suggests that the carboxyl two thirds of the C protein have a functional importance. We also found a highly variable region between the L coding frame and the 5' trailer sequence. The relevance of these findings to actual viral replication should be clarified in the future.

Base Sequence↗
PubMed2001

Impact of repeat hepatectomy on recurrent colorectal liver metastases.

BACKGROUND: Hepatic recurrence is seen in approximately 40% of patients undergoing hepatectomy for colorectal metastases. This study was designed to assess the risks and clinical benefits of repeat hepatectomy for those patients. METHODS: Twenty-six patients underwent repeat hepatectomy for hepatic recurrence, and their clinical data were retrospectively reviewed for operative morbidity and mortality, performance level, and survival. RESULTS: There was no operative mortality after repeat hepatectomy. Operative bleeding was significantly increased in the second hepatectomy; but operating time, duration of hospital stay, and performance status after the second hepatectomy were comparable with those of the initial hepatectomy. The median survival time from the second hepatectomy was 31 months, and the 3- and 5-year survival rates were 62% and 32%, respectively. A short disease-free interval (6 months or less) between the initial hepatectomy and diagnosis of hepatic recurrence in the remnant liver was significantly associated with poor survival after the second hepatectomy. CONCLUSIONS: Repeat resection contributed to clinical benefits for selected patients with hepatic recurrence after the initial hepatectomy for colorectal liver metastases. However, appearance of hepatic recurrence within 6 months or less after the initial hepatectomy is a poor prognostic factor for repeat hepatectomy.

Adult↗
PubMed2001

Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes.

Liver-expressed chemokine (LEC)/CCL16 is a human CC chemokine selectively expressed in the liver. Here, we investigated its receptor usage by calcium mobilization and chemotactic assays using mouse L1.2 pre-B cell lines stably expressing a panel of 12 human chemokine receptors. At relatively high concentrations, LEC induced calcium mobilization and chemotaxis via CCR1 and CCR2. LEC also induced calcium mobilization, but marginal chemotaxis via CCR5. Consistently, LEC was found to bind to CCR1, CCR2 and CCR5 with relatively low affinities. The binding of LEC to CCR8 was much less significant. In spite of its binding to CCR5, LEC was unable to inhibit infection of an R5-type HIV-1 to activated human peripheral blood mononuclear cells even at high concentrations. In human liver sections, hepatocytes were strongly stained by anti-LEC antibody. HepG2, a human hepatocarcinoma cell line, was found to constitutively express LEC. LEC was also present in the plasma samples from healthy adult donors at relatively high concentrations (0.3--4 nM). Taken together, LEC is a new low-affinity functional ligand for CCR1, CCR2 and CCR5, and is constitutively expressed by liver parenchymal cells. The presence of LEC in normal plasma at relatively high concentrations may modulate inflammatory responses.

Animals↗
PubMed2001

Mucosal barrier and immune mediators.

The intestinal mucosa functions is an immunologic organ that plays a major role in the development of oral tolerance and host-defense mechanisms. Antigens must cross the intestinal epithelium in a controlled manner to interact with dendritic antigen-presenting cells, because bacteria or their products are a primary risk factor for the development of intestinal inflammation. Therefore, the regulation of the intestinal epithelial cell barrier is central to the development of intestinal immunity and inflammation, but the involved mechanisms are largely unknown. Intestinal barrier function relies on the formation of tight junctions at the apical contact areas of intestinal epithelial cells. Tight junctions have a highly dynamic structure whose permeability, assembly, or disassembly can be regulated by a variety of cellular and metabolic mediators, including cytokines, which have major functions in the immune system. Immune modulators control tight junction dependent intestinal barrier function during development, wound healing, and pathologic processes such as cancer, infection, and chronic inflammation.

Journal Article↗
PubMed2000

Dissociation and recombination between ligands and heme in a CO-sensing transcriptional activator CooA. A flash photolysis study.

CooA from Rhodospirillum rubrum is a transcriptional activator in which a heme prosthetic group acts as a CO sensor and regulates the activity of the protein. In this study, the electronic relaxation of the heme, and the concurrent recombination between ligands and the heme at approximately 280 K were examined in an effort to understand the environment around the heme and the dynamics of the ligands. Upon photoexcitation of the reduced CooA at 400 nm, electronic relaxation of the heme occurred with time constants of 0.8 and 1.7 ps. The ligand rebinding was substantially completed with a time constant of 6.5 ps, followed by a slow relaxation process with a time constant of 173 ps. In the case of CO-bound CooA, relaxation of the excited heme occurred with two time constants, 1.1 and 2.4 ps, which were largely similar to those with reduced CooA. The subsequent CO recombination process was remarkably fast compared with that of other CO-bound heme proteins. It was well described as a biphasic geminate recombination process with time constants of 78 ps (60%) and 386 ps (30%). About 10% of the excited heme remained unligated at 1.9 ns. The dynamics of rebinding of CO thus will help us to understand how the physiologically relevant diatomic molecule approaches the heme binding site in CooA with picosecond resolution.

Bacterial Proteins↗
PubMed2000

The roles of platelet-activating factor and endothelin-1 in renal damage after total hepatic ischemia and reperfusion.

BACKGROUND: This study was designed to verify the involvement of platelet-activating factor (PAF) in renal damage associated with hepatic ischemia and reperfusion (HIR) injury through the release of endothelin (ET)-1 and to determine the modulating effect of a specific PAF receptor antagonist on these insults in rats. METHODS: Male rats pretreated with either normal saline as a vehicle (NS group) or intravenous TCV-309, a PAF receptor antagonist (TCV group), were subjected to 120 min of total hepatic ischemia under an extracorporeal portosystemic shunt. Plasma aspartate transaminase, creatinine, blood urea nitrogen, and ET-1 levels and the relative renal wet weight were determined under nonischemic conditions and at 1, 3, and 6 hr of reperfusion after hepatic ischemia. Changes in mean arterial blood pressure and renal tissue blood flow measurements in the kidney were determined throughout the experiment. RESULTS: Increased plasma aspartate transaminase, creatinine, blood urea nitrogen, and ET-1 levels and the relative renal wet weight after HIR in the NS group were significantly suppressed by TCV-309 pretreatment. Mean arterial blood pressure and renal tissue blood flow after HIR in the TCV group were significantly improved when compared with those in the NS group. These effects resulted in attenuation of structural hepatic and renal damage with the improvement of 7-day survival (62%). CONCLUSIONS: The present study demonstrates that renal damage as well as critical liver injury is produced after reperfusion following 120 min of total hepatic ischemia. A PAF receptor antagonist may be therapeutically useful to protect against these types of damage via indirect modulation of plasma ET-1 levels.

Animals↗
PubMed2000

Early experience of aortic valve replacement with the Freestyle stentless aortic bioprosthesis in elderly patients.

OBJECTIVES: Stentless bioprostheses have been gaining popularity in recent years as hemodynamically superior alternatives to conventional stented bioprostheses. METHODS: Between July 1996 and November 1998, 13 patients with aortic valve disease, 7 males and 6 females with a mean age (+/- SD) of 68 +/- 5 years, underwent an aortic valve replacement using the Medtronic Freestyle aortic bioprosthesis. The predominant lesions were stenosis in 8 patients and regurgitation in 5, while 2 patients had endocarditis. The operation was performed by a subcoronary technique in 9, root-inclusion technique in 3, and full root technique in 1 patient. RESULTS: Throughout the follow-up periods (with average follow-up period of 20.6 months), there was no hospital mortality, though there was one late death of unknown cause. The New York Heart Association class improved in all patients. The peak transvalvular gradient decreased from 18.4 +/- 9.8 to 12.6 +/- 9.6 mmHg, and the effective valve orifice area increased from 2.30 +/- 0.96 to 2.59 +/- 1.05 cm2 between the 1-month and the 6-month follow-up examinations. In patients with aortic regurgitation, the left ventricular end-diastolic/end-systolic volume index significantly decreased from 147 +/- 36/62 +/- 19 to 73 +/- 26/33 +/- 14 ml/m2 at 1 month after the operation. The left ventricular mass index also significantly decreased from 189 +/- 26 to 143 +/- 30 g/m2 in patients with aortic regurgitation and from 171 +/- 28 to 144 +/- 30 g/m2 in those with aortic stenosis. CONCLUSIONS: Although long-term follow-up is required for further evaluation, the early results appeared to indicate that the Freestyle aortic bioprosthesis was suitable for elderly patients requiring aortic valve replacement.

Aged↗
PubMed2000

Percutaneous cardiopulmonary support with heparin-coated circuits in postcardiotomy cardiogenic shock. Efficacy and comparison with left heart bypass.

OBJECTIVE: Percutaneous cardiopulmonary support, a simplified form of venoarterial bypass, using totally heparin-coated circuits, has recently come into clinical use. To clarify its efficacy in postcardiotomy cardiogenic shock to aid weaning from cardiopulmonary bypass, we compared results of percutaneous cardiopulmonary support with those of left heart bypass using a centrifugal pump. METHODS: We reviewed 18 patients treated between 1991 and 1998 who could not be weaned from cardiopulmonary bypass. Nine were aided by totally heparin-coated percutaneous cardiopulmonary support (PCPS group), and 9 supported by left heart bypass using a centrifugal pump (LHB group). In both groups, activated clotting time was controlled at 150-200 seconds using minimal doses of heparin as needed. RESULTS: Weaning and survival rates were higher in the PCPS group than in the LHB group (100% vs 55.6%, and 66.7% vs 22.2%). The PCPS group had a smaller amount of blood loss and needed a smaller amount of blood components in the immediate postoperative period. One percutaneous cardiopulmonary support patient required surgical re-exploration for postoperative bleeding (11.1%), but no clinical thromboembolic event occurred in the PCPS group. In the LHB group, 5 patients underwent surgical re-exploration for postoperative bleeding (55.6%), and 2 underwent thrombus extirpation in the left ventricle (22.2%). CONCLUSIONS: Although this study was retrospective and historical backgrounds could have been involved, our data suggest that totally heparin-coated percutaneous cardiopulmonary support system appears more effective as an aid to weaning from cardiopulmonary bypass and in short-term circulatory support for patients in postcardiotomy cardiogenic shock.

Adult↗
PubMed2000

Marginal ulceration after pylorus-preserving pancreaticoduodenectomy.

Marginal ulceration is a serious problem after both standard pancreaticoduodenectomy (PD) and pylorus-preserving pancreaticoduodenectomy (PPPD). The relationship between this complication and the method of reconstruction after PPPD was analyzed in this study. Patients who underwent standard PD (n = 72) or PPPD (n = 28) in the 20-year period from 1978 to 1997 were retrospectively reviewed. After PPPD, 4 patients (14.3%) developed marginal ulceration on the jejunal side of the duodenojejunal anastomosis, while none of the patients had marginal ulceration after standard PD. The marginal ulcer occurred in 3 of 14 patients treated with the Roux-en-Y method, and in 1 of 9 treated with pancreatogastrostomy. In the Roux-en-Y method, the anal jejunal loop anastomosed to the bulb was directly exposed to gastric juice without neutralization by pancreatic juice from the oral jejunal limb. Of the 4 patients with marginal ulceration, 2 of those treated by the Roux-en-Y method required gastrectomy; the other 2 patients were treated medically. Our analysis of the literature showed that the Roux-en-Y method had the highest incidence of marginal ulcerations. The gastrointestinal reconstruction method without a mixture of gastric juice and pancreatic juice may be a causal factor in the marginal ulceration that occurs after PPPD. In reconstruction after PPPD, we should not create a jejunal loop that is exposed to gastric juice alone.

Aged↗
PubMed2000

Portal vein thrombosis caused by microwave coagulation therapy for hepatocellular carcinoma: report of a case.

Microwave coagulation therapy (MCT) is one of the treatment modalities for patients with hepatocellular carcinoma (HCC). A 67-year-old man with liver cirrhosis underwent MCT during a laparotomy for a deeply located HCC (2.5 cm in diameter) at the border of the anterior and posterior segments of the right hepatic lobe. Two weeks after MCT, he complained of abdominal fullness. Portal vein thrombosis (PVT) was diagnosed because he had massive ascites and an echogenic mass in the portal vein on abdominal ultrasonography. PVT was successfully treated by fibrinolytic therapy with a selective infusion of urokinase via the superior mesenteric artery (SMA). There have been few reports on PVT as a complication of MCT. Attention should be paid to the possible occurrence of PVT as a critical complication after MCT for liver tumors adjacent to the portal vein. Fibrinolytic therapy via the SMA is thus considered to be an effective approach for PVT after MCT.

Aged↗
PubMed2000

Lymphoepithelial cyst of the pancreas: report of a case.

An extremely rare case of a lymphoepithelial cyst (LEC) of the pancreas is described herein. A pancreatic cystic tumor was initially detected in a 50-year-old man at a medical checkup. On admission, his serum carbohydrate antigen (CA) 19-9 level was 8100 U/ml and a computed tomography scan revealed a well-circumscribed multilocular cystic tumor in the pancreatic head and body. Magnetic resonance cholangiopancreatography showed no communication between the pancreatic ducts and the tumor. A distal pancreatectomy with lymph node dissection was performed because the lesion was suspected to be a mucinous cystadenoma or cystadenocarcinoma of the pancreas. However, histological examination revealed that the cyst was lined by stratified squamous epithelium and surrounded by lymphoid tissue. thereby confirming the diagnosis of LEC of the pancreas. The superficial layer of squamous epithelium and the cystic contents were found to be immunohistologically positive for CA19-9. Establishing a preoperative diagnosis of LEC is quite difficult because it resembles other cystic neoplasms of the pancreas in radiographic features and is frequently associated with an elevation of serum tumor markers such as CA19-9.

Biomarkers, Tumor↗
PubMed2000

Intracystic hemorrhage of pancreatic serous cystadenoma after renal transplantation: report of a case.

Immunosuppressive therapy after transplantation increases the risk of developing neoplasms, and neoplasms of the digestive organs are very common in Asia. We experienced a patient with an intracystic hemorrhage of pancreatic serous cystadenoma during the follow-up after renal transplantation. Pancreatic cystadenomas are not frequent. Only two cases, presenting with acute abdomen, have so far been reported in the literature. The intracystic hemorrhage in our case may have been related to a rapid tumor growth due to weakened antitumor immunity and azathioprine-induced pancreatitis.

Adult↗
PubMed2000

Accelerated growth signals and low tumor-infiltrating lymphocyte levels predict poor outcome in T4 esophageal squamous cell carcinoma.

BACKGROUND: Little is known about the biological nature of T4 esophageal carcinoma growth signals and host defenses. METHODS: Paraffin-embedded sections from 78 patients with T2 to T4 esophageal squamous cell carcinoma who underwent operation were analyzed with immunohistochemistry. RESULTS: Positive cyclin A showed a significantly greater increase in T4 tumors than in those of other stages, and negative p27 showed a significantly greater decrease in T4 tumors than in large T3 stage tumors (tumor size > or = 4.0 cm). Patients with low-grade tumor-infiltrating lymphocyte (TIL) density showed a significantly greater decrease in T4 than in T2. The combination of p27 and cyclin A was a significant independent prognostic factor among T and N factors in multivariate analysis. TIL density was an independent prognostic factor among immunonutritional variables such as serum albumin concentration and the number of total blood lymphocytes. CONCLUSIONS: T4 esophageal squamous cell carcinoma has a poor prognosis, which is associated with increased p27-negative and cyclin A-positive growth signals in the tumor and with low TIL density in the host.

Apoptosis↗