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T Sakaguchi

Publications and source records attributed to T Sakaguchi.

At least 127 records · Page 7Linked to original sources
PubMed1997

[Structure and function of the influenza virus M2 ion channel protein].

The M2 protein of influenza virus A is an integral membrane protein that is expressed on the infected cell surface and incorporated into virions. This protein is a minor component in virions but plays an essential role in the viral life cycle. The M2 protein, which forms a homotetramer, has H+ ion channel activity that is sensitive to an anti-influenza virus drug, amantadine, and is activated by low pH. When the virus enters cells, the M2 ion channel is activated in endosomes to acidify inside the virion, facilitating viral uncoating. The M2 channel also modifies the pH of the intracellular compartments to protect newly synthesized hemagglutinin from irrelevant low pH-induced conformational change for some influenza viruses.

Amantadine↗
PubMed1996

Surgical treatment of patients with mixed hepatocellular carcinoma and cholangiocarcinoma.

BACKGROUND: The results of treatment of mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) remain unclear because of the rarity of this disease. METHODS: Of 218 patients with primary liver carcinoma treated from 1979 to 1995, 6 had a histologic diagnosis of mixed HCC and CC (MHC). Five had chronic liver disease. Serum carcinoembryonic antigen (CEA), CA 19-9, and alpha-fetoprotein (AFP) levels were determined and hepatic angiography was performed preoperatively. Left trisegmentectomy (with portal vein reconstruction) and extended right lobectomy were performed in one patient each, whereas selective subsegmentectomy was done in three patients, and partial resection of segment 3 in one patient. Hilar lymphadenectomy was performed in two patients. RESULTS: Mild liver dysfunction was observed in two patients. The resected tumors ranged from 2.7 to 12 cm in size and all showed intermingling of HCC and CC elements. A preoperative diagnosis of MHC was possible in one patient because of a high AFP level and hypovascularity, whereas a high CEA level and hypervascularity led to the diagnosis in another patient. High levels of AFP, CEA, and CA 19-9 were observed in three, one, and three patients, respectively. There were no metastases in the dissected lymph nodes. Although 2 patients had died by 2 years after surgery, the 5-year survival rate was 60% and there were 2 long term survivors for more than 10 years. CONCLUSIONS: A hypervascular tumor with high CEA and CA 19-9 levels or a hypovascular tumor with a high AFP level may suggest a preoperative diagnosis of MHC in patients with suspected HCC. Extensive surgery is an effective treatment for this disease, except in patients with satellite nodules. Hilar lymphadenectomy may not be necessary in selected patients.

Adult↗
PubMed1996

Proliferating cell nuclear antigen in neurones: induction by u.v. irradiation.

Proliferating cell nuclear antigen (PCNA) plays a pleiotropic role in DNA replication, excision repair of injured DNA and apoptosis. We found that PCNA protein is expressed predominantly in CA3 pyramidal neurones in hippocampal slices cultured from 1-week-old rats. Immunoblotting analysis revealed that this PCNA expression is enhanced by u.v. irradiation with no effect on neuronal viability. These results suggest that expression of PCNA in non-proliferating central neurones is associated with repair of injured DNA.

Animals↗
PubMed1996

Suppression of hepatic portal blood flow caused by carbon dioxide pneumoperitoneum can be restored after dopamine administration in pigs.

Portal venous blood flow (PVF), hepatic arterial blood flow (HAF) and systemic arterial pressure (SAP) were examined after dopamine (DA) injection into the jugular vein under carbon dioxide pneumoperitoneum in pigs. When intraabdominal pressure (IAP) was increased by 12 mmHg, PVF and HAF were reduced, but SAP was unchanged. When IAP was kept at 12 mmHg, the injection of DA at 10 micrograms/kg/min for 2 min produced an increase in PVF without causing any change in HAF or SAP. The response in PVF was dose-dependent. When IAP was increased to 16 mmHg, PVF response was diminished, and no change in HAF or SAP was seen at the same dose of DA. These observations suggest that DA is effective in increasing PVF under enhanced IAP conditions, but such circulatory improvement due to the agent would be prominent when IAP is below 12 mmHg.

Animals↗
PubMed1996

Indocyanine green disappearance enhanced by prostaglandin E1 in patients with hepatic resection.

Indocyanine green (ICG) is a reliable indicator reflecting hepatocyte function and hepatic blood flow. Prostaglandin E1 (PGE) has been indicated to increase hepatic blood flow and protect the hepatocyte. The purpose of this study is to investigate whether PGE influences the ICG disappearance rate in patients with hepatic resection. Eleven patients with hepatic resection were divided into two groups according to the presence of liver cirrhosis (LC, n = 4) and chronic hepatitis (CH, n = 7). ICG 0.1 mg/kg was given as an intravenous bolus into the cubital vein 5 min after PGE administration, then the disappearance rate of ICG (ICG-K) was determined by a finger monitoring method. PGE administration increased ICG-K in the LC and CH groups with normal liver function, and the ICG-K response was dose dependent when the dosage of PGE ranged from 0.01 to 0.05 microg/kg/min. When ICG-K relative to the ICG-K of the control was defined as the ICG-K ratio, the daily course of the ratio in the LC group was higher than in the CH group. PGE increases the ICG-K of patients with normal liver function before and after hepatic resection, and this is evident in the case of liver cirrhosis.

Aged↗
PubMed1996

Hepatic angiomyolipoma developing during the follow-up of ulcerative colitis: report of a case and review of the literature.

Hepatic angiomyolipoma is a rare tumor composed of spindle-shaped and epithelioid smooth muscle cells, adipose tissue, and proliferating blood vessels. We report the first documented case of this tumor developing in a patient with ulcerative colitis. A solitary tumor (7.5 x 7.5 x 7 cm) was detected in the left lateral segment of the liver and a left hepatic lobectomy was performed. The diagnosis of angiomyolipoma was confirmed by a pathological examination. We also review the literature on previously reported cases of hepatic angiomyolipoma.

Adult↗
PubMed1996

Enhancement of portal blood flow by ursodesoxycholic acid in partially hepatectomized rats.

Portal venous flow (PVF) was examined after portal injection of ursodesoxycholic acid (URSO) in rats that were partially hepatectomized by either 40% or 66%. URSO (10 mg/kg per minute) was injected into the portal vein and was thereafter observed to increase PVF concomitantly with a fall in portal vein and was thereafter observed to increase PVF concomitantly with a fall in portal venous pressure (PVP) in control animals. The increase in PVF in response to URSO was dose-dependent. In hepatectomized rats, the PVF response was augmented when the same dose of URSO was portally injected, and the magnitude of response was enhanced in proportion to the volume of liver resected. These results suggest that URSO increases PVF through vasodilation of the portal vessels, and therefore URSO is considered to increase PVF potently in a partially hepatectomized condition.

Animals↗
PubMed1996

Effect of prostaglandin E1 on ammonia concentration in blood of patients with hepatic resection.

Plasma concentrations of ammonia were examined following prostaglandin E1 (PGE1) administration in 16 patients who received hepatectomy for hepatocellular carcinoma. PGE1 at 0.01-0.04 microgram/kg/min was administered for approximately 24 hr during the perioperative periods. The ammonia concentration was reduced a day after the operation following intravenous administration of PGE1 in cirrhotic patients compared to noncirrhotic patients with or without PGE1 injection. Serum liver function scores, glutamic pyruvic transaminase, and total bilirubin concentrations were decreased after PGE1 administration. A similar ammonia response due to PGE1 was obtained after operation in cirrhotic patient when PGE1 0.5 microgram/kg was administered intravenously for 30 min. These results suggest that PGE1 administration is useful in reducing the enhanced ammonia concentration associated with hepatic resection, and it is particularly effective in the case of liver cirrhosis.

Alanine Transaminase↗
PubMed1996

Second cancer during long-term survival after resection of biliary tract carcinoma.

Curative surgery for biliary tract malignancy has improved the prognosis of patients; however, during long-term follow up after extensive surgery, four of our patients (two with gallbladder carcinoma and two with bile duct carcinoma) developed a second primary cancer (one each in the duodenum, skin, descending colon, and lung). Regular examination of the upper gastrointestinal tract, colorectum, and lungs, and testing for tumor markers (carcinoembryonic antigen and CA19-9) were performed as follow-up studies. As a result, the second cancers were all found at a relatively early stage and all four patients are still alive 6-14 years after the initial operation. A review of the annual autopsy reports over the last 5 years in Japan showed that the incidence of second cancer was 14.8% in patients with gallbladder carcinoma and 13.5% in those with bile duct carcinoma. Furthermore, the rate of second gastric and colorectal carcinoma was significantly higher in patients with primary bile duct cancer than in those with primary gallbladder cancer. In conclusion, the incidence of a second cancer after resection of biliary tract malignancy is more than 10%, but this second cancer can be detected relatively easily and treated at an early stage during the course of regular long-term follow up for the first cancer.

Adult↗
PubMed1996

Binding of nonamer peptides to three HLA-B51 molecules which differ by a single amino acid substitution in the A-pocket.

The interaction between 9-mer peptides and HLA-B51 molecules was investigated by quantitative peptide binding assay using RMA-S cells expressing human beta2-microglobulin and HLA-B51 molecules. Of 147 chemically synthesized 9-mer peptides possessing two anchor residues corresponding to the motif of HLA-B*5101 binding self-peptides, 27 peptides bound to HLA-B*5101 molecules. Pro and Ala at position 2 as well as Ile at position 9 were confirmed to be main anchor residues, while Gly at position 2 as well as Val, Leu, and Met at position 9 were weak anchor residues for HLA-B*5101. The A-pocket is suspected to have a critical role in peptide binding to MHC class I molecules because this pocket corresponds to the N-terminus of peptides and has a strong hydrogen bond formed by conserved Tyr residues. Further analysis of peptide binding to HLA-B*5102 and B*5103 molecules showed that a single amino acid substitution of Tyr for His at residue 171(B*5102) and that of Gly for Trp at residue 167 (B*5103) has a minimum effect in HLA-B51-peptide binding. Since previous studies showed that some HLA-B51 alloreactive CTL clones failed to kill the cells expressing HLA-B*5102 or HLA-B*5103, these results imply that the structural change of the A-pocket among HLA-B51 subtypes causes a critical conformational change of the epitope for TCR recognition rather than influences the interaction between peptides and MHC class I molecules.

Amino Acid Sequence↗
PubMed1996

Role of Kupffer cells and the spleen in modulation of endotoxin-induced liver injury after partial hepatectomy.

The hypothesis that both activated Kupffer cells and the spleen may be responsible for endotoxin-induced liver injury following partial hepatectomy was investigated. Male rats were divided into a sham group receiving laparotomy alone and three groups receiving a two-thirds hepatectomy; one group was given normal saline (NS) solution as a vehicle control, one group received intravenous gadolinium chloride (GC group) (7 mg/kg body weight) for 2 days before intravenous injection of endotoxin to inhibit Kupffer cell phagocytosis, and the third group simultaneously underwent splenectomy and partial hepatectomy (SH group). As endotoxin, lipopolysaccharide (LPS) (1 mg/kg body weight) was administered intravenously 2 days after surgery. In the GC and SH groups, phagocytic activity was reduced to approximately 40% of that in the sham group. The highest plasma tumor necrosis factor alpha (TNF-alpha) level (8,544 +/- 1,223 pg/mL) was observed in the NS group at 1 hour after LPS administration, and the level was significantly reduced by GdCl3 or splenectomy (P < 0.05). Inhibition of Kupffer cell function and splenectomy attenuated functional and structural liver damage associated with the decreased hepatic infiltration of polymorphonuclear leukocytes (PMNs) and reduced priming of circulating PMNs in the early stage of endotoxemia following partial hepatectomy. Consequently, the 24-hour survival rate of the SH and GC groups was significantly improved to 50% and 80%, respectively (P < .05), while that of the NS group was 12.5%. These findings indicate that the modification of inflammatory mediator generation by splenectomy or inhibition of Kupffer cell function may be beneficial for the prevention of endotoxin-induced liver injury after partial hepatectomy.

Animals↗
PubMed1996

The ion channel activity of the influenza virus M2 protein affects transport through the Golgi apparatus.

High level expression of the M2 ion channel protein of influenza virus inhibits the rate of intracellular transport of the influenza virus hemagglutinin (HA) and that of other integral membrane glycoproteins. HA coexpressed with M2 is properly folded, is not associated with GRP78-BiP, and trimerizes with the same kinetics as when HA is expressed alone. Analysis of the rate of transport of HA from the ER to the cis and medial golgi compartments and the TGN indicated that transport through the Golgi apparatus is delayed. Uncleaved HA0 was not expressed at the cell surface, and accumulation HA at the plasma membrane was reduced to 75-80% of control cells. The delay in intracellular transport of HA on coexpression of M2 was not observed in the presence of the M2-specific ion channel blocker, amantadine, indicating that the Golgi transport delay is due to the M2 protein ion channel activity equilibrating pH between the Golgi lumen and the cytoplasm, and not due to saturation of the intracellular transport machinery. The Na+/H+ ionophore, monensin, which also equilibrates pH between the Golgi lumen and the cytoplasm, caused a similar inhibition of intracellular transport as M2 protein expression did for HA and other integral membrane glycoproteins. EM data showed a dilation of Golgi cisternae in cells expressing the M2 ion channel protein. Taken together, the data suggest a similarity of effects of M2 ion channel activity and monensin on intracellular transport through the Golgi apparatus.

Animals↗
PubMed1996

Role of HLA-B*5101 binding nonamer peptides in formation of the HLA-Bw4 public epitope.

HLA-Bw4 is one of two HLA-B public epitopes which are discriminated by specific alloantisera and mAb. It is believed that the 77-83 of HLA-B molecules form the Bw4 epitope recognized by specific antibodies. This epitope is also recognized by NKB1 receptors on NK cells. We investigated the role of a peptide bound to HLA-B molecules on the formation of the Bw4 epitope recognized by two HLA-Bw4-specific mAb, TU109 and TU48, which recognized the difference of the Bw4 epitope among HLA-B52, -B52 and -B53. Recognition of the HLA-B*5101-peptide complex by these mAb was examined using a panel of HLA-B*5101 binding nonamer peptides. The sequence of HLA-B*5101 binding peptides has a minimum influence on the binding of TU48 mAb to HLA-B*5101 molecules. In contrast, the binding of TU109 mAb to HLA-B*5101 molecules was critically influenced by the sequence of a peptide bound to HLA-B*5101 molecules. TU109 mAb did not recognize HLA-B*5101 binding peptides carrying small or negatively charged residues at P8. The results were confirmed by a panel of mutant peptides at P8. Taken together, these results indicate that a positively charged or neutralized side chain of P8 is critical for the epitope formation of Bw4 recognized by this mAb.

Animals↗
PubMed1996

Hepatic HCV-RNA as a predictor of outcome after interferon therapy in patients with chronic hepatitis C.

Measurement of serum HCV-RNA is a useful index for evaluating the antiviral effect of interferon therapy in chronic hepatitis C. In the present study, we investigated whether the detection of hepatic HCV-RNA after interferon treatment, using a polymerase chain reaction assay, predicted long-term response to therapy in patients with chronic hepatitis C. Thirty-three patients underwent liver biopsies before and after interferon therapy. Histology and clinical courses were compared after treatment. Before therapy, serum and hepatic HCV-RNA was detected in specimens from 32 (97%) and 33 (100%) patients, respectively. Serum HCV-RNA became undetectable in samples from 22 (67%) patients; however, in 10 of these patients (45%), serum HCV-RNA levels relapsed after therapy. Hepatic HCV-RNA became undetectable in 14 patients after therapy and the serum aminotransferase concentration remained within normal limits during and following (24-92 weeks) therapy in 12 of these patients (86%). All 11 patients with detectable hepatic HCV-RNA also had serum HCV-RNA and elevated aminotransferase concentrations refractory to therapy. The absence of hepatic HCV-RNA at the end of interferon treatment thus predicted a long-term complete response to therapy with a sensitivity of 100%, a specificity of 90% and an accuracy of 94%. We conclude that hepatic rather than serum HCV-RNA is a more useful index for the prediction of the long-term efficacy of interferon therapy.

Adult↗
PubMed1996

Efficacy of ursodeoxycholic acid in combination with interferon-alpha in treating chronic hepatitis C: results of a long-term follow-up trial.

Ursodeoxycholic acid (UDCA) has recently been combined with interferon (IFN) in the treatment of individuals with chronic hepatitis C. However, whether its addition results in a long-term favourable response to IFN remains unclear. A prospective randomized trial of IFN alone versus IFN plus UDCA was therefore undertaken in 52 patients with chronic hepatitis C. All patients received a 24 week course of IFN-alpha (6 x 10(6) U/day for 2 weeks and then three times a week for 22 weeks) and half also received UDCA (600 mg/day) with IFN and then alone for 48 additional weeks. Normalization of serum alanine transaminase (ALT) concentrations at 0, 24 and 48 weeks after cessation of IFN therapy was apparent in 77, 42 and 42% of patients in the IFN-alone group and in 77, 54 and 42% of patients in the IFN plus UDCA group, respectively. There was no significant difference between the two groups with regard to response rate to IFN and the addition of UDCA to IFN treatment had no significant effect on hepatitis C virus (HCV) viraemia. During the follow-up period, 10 of 20 patients with normal serum ALT at the end of IFN treatment relapsed in the IFN-alone group compared with 11 of 20 patients in the IFN plus UDCA group. Among these relapsed patients, serum ALT concentration was significantly lower in the IFN plus UDCA group than in the IFN-alone group during the follow-up period. Twenty-four weeks after cessation of IFN therapy, the percentage of patients with HCV-RNA in their serum who showed a normalization of serum ALT concentrations was significantly higher in the IFN plus UDCA group than in the IFN-alone group (44 vs 6%). Thus, although the addition of UDCA was not associated with a favourable long-term response to HCV viraemia, it did reduce the risk and the severity of relapse following the cessation of IFN therapy.

Alanine Transaminase↗
PubMed1996

A new silicon detector telescope for measuring the linear energy transfer distribution over the range from 0.2 to 400 keV/micrometer in space.

A new telescope consisting of three two-dimensional position-sensitive silicon detectors which can measure the linear energy transfer (LET) distribution over the range from 0.2 to 400keV/micrometers has been developed as a real-time radiation monitor in manned spacecraft. First, the principle of LET measurement and its design method are described. Second, suitable electronic parameters for the LET measurement are experimentally determined. Finally the telescope performance is investigated by using, relativistic heavy ions. The first in-flight test of this type of telescope on the US Space Shuttle (STS-84) is scheduled for May, 1997.

Astronomy↗