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Biomedical subjects

T Sakaguchi

Publications and source records attributed to T Sakaguchi.

At least 91 records · Page 5Linked to original sources
PubMed1999

[A case of advanced gastric cancer successfully treated by neoadjuvant chemotherapy with CPT-11, CDDP and 5-FU].

A patient with advanced gastric cancer was treated with combined administration of CPT-11 CDDP and 5-FU before operation. CPT-11 was given intravenously at a dose of 30 mg/m2/day on day 1 and day 8. At the same time, 5 mg/m2/day CDDP and 350 mg/m2/day 5-FU were infused for 2 weeks. The patient experienced no other adverse reaction than a mild degree of nausea. Histological examination of the resected specimen revealed complete disappearance of cancer cells both in the stomach and the regional lymphnodes.

Adult↗
PubMed1998

Prognostic value of cyclin E and p53 expression in gastric carcinoma.

BACKGROUND: Cyclins and wild-type p53 are prime cell cycle regulators and may be involved in tumorigenesis. Cyclin E is a late G1 cyclin and its abnormalities have been reported in several cancers. The authors investigated the correlation between cyclin E expression and progression of gastric carcinoma. METHODS: The expression of cyclin E and p53 proteins was investigated retrospectively in 116 patients with gastric carcinoma. Immunohistochemical staining of the paraffin sections was performed using monoclonal antibodies to cyclin E and p53. RESULTS: The total cyclin E positive rate was 44.0% (51 of 116) of all cases, 26 of which were strongly positive. Strong cyclin E expression frequently was observed in deeply invasive tumors, tumors with lymph node metastasis, and tumors of advanced stage. The incidence of p53 expression was higher in the cyclin E positive tumors than in the other tumors. With regard to prognosis, patients whose tumors had both strong positivity for cyclin E and positivity for p53 had significantly poorer prognosis. In multivariate analysis, the combined variable of cyclin E and p53 was an independent prognostic indicator together with serosal invasion and tumor size. CONCLUSIONS: These data suggest the cyclin E expression correlates with p53 expression and may contribute to the progression of gastric carcinoma. The combined variable of cyclin E and p53 expression could be a useful prognostic indicator in patients with gastric carcinoma.

Adult↗
PubMed1998

Pathophysiological appraisal of a rat model of total hepatic ischemia with an extracorporeal portosystemic shunt.

BACKGROUND: Animal models of total hepatic ischemia (THI) and reperfusion injury are restricted by concomitant splanchnic congestion. This study was performed to determine the requirement suitable for an extracorporeal portosystemic shunt (PSS) to maintain the intestinal integrity in a rat model of THI. MATERIALS AND METHODS: Using a polyethylene tube (0.86 or 1 mm i.d.), PSS was placed between the mesenteric and jugular veins. Comparison was done between THI models with or without PSS and a partial ischemia model with hepatectomy of the nonischemic lobes. Well-tolerated hepatic ischemic period, portal pressure after 10 min of hepatic ischemia, portal endotoxin levels at 1 h after reperfusion, histological features of the small bowel just before reperfusion, and local jejunal and ileal blood hemoglobin oxygen saturation index (ISO2) were compared among the models. RESULTS: Animals without PSS poorly tolerated 30 min of THI. Animals receiving THI with PSS or partial hepatic ischemia tolerated a longer ischemic period (60 min) with a significantly higher small bowel ISO2, lower portal pressure and endotoxin levels (P < 0.01), and less histological damage of the small bowel when compared to those receiving THI without PSS. Portal endotoxin levels after THI with PSS using a 1-mm i.d. tube as well as partial hepatic ischemia were significantly lower than those after THI with PSS using a 0.86-mm i.d. tube. CONCLUSIONS: THI with PSS using a 1-mm i.d. tube was strikingly similar to partial hepatic ischemia in the pathophysiological profile during hepatic ischemia. PSS with a tube 1 mm or more in inner diameter offers pathophysiological advantages in experiments on THI and reperfusion.

Animals↗
PubMed1998

Crucial role of N-terminal residue of binding peptides in recognition of the monoclonal antibody specific for the peptide-HLA-B5, -B35 complex.

The monoclonal antibody (mAb) 4D12 specific for the HLA-B5, -B35 cross-reacting group (CREG) bound to a fraction of HLA-B*3501 and HLA-B*5101 molecules carrying self-peptides. Analysis of the binding of mAb 4D12 to HLA-B*3501 and -B*5101 molecules pulsed with chemically synthesized peptides revealed that this mAb recognizes a restricted number of peptides and that P1 of the bound peptides critically influences its binding. The 4D12 mAb bound only to HLA-B*3501 molecules carrying peptides with Asn, Asp, Glu, Ser, and Val at P1. Analysis using an HLA-B*3501 crystallographic model suggested that 4D12 may recognize the side chain of the P1 residue that is pointing to the solvent. On the other hand, 4D12 bound only to HLA-B*5101 molecules carrying peptides with Asn or Asp at P1, suggesting that the 4D12 epitope formed by Glu, Ser, or Val at P1 and the A-pocket was changed by the substitution of His for Tyr at residue 171 of HLA-B*3501 molecules. This was confirmed by testing the binding of mAb 4D12 to HLA-B*3501 mutant molecules at residue 171 carrying these peptides. These results together suggest that the conformation of the A-pocket and its hydrogen bound network with the P1 residue is also critical for the binding of mAb 4D12. The present study shows the molecular basis of the specificity of 4D12 for the peptide-HLA class I complex.

Amino Acid Sequence↗
PubMed1998

Properties of a cold-active protease from psychrotrophic Flavobacterium balustinum P104.

Protease activity was detected in the culture medium of Flavobacterium balustinum P104 grown at 10 degrees C, which was isolated from salmon (Oncorhynchus keta) intestine. The enzyme, designated as CP-70 protease, was purified to homogeneity from the culture broth by ion exchange and gel filtration chromatographyies. The molecular mass of the protease was 70 kDa, and its isoelectric point was close to 3.5. Maximal activity toward azocasein was observed at 40 degrees C and from pH 7.0 to 9.0. The activity was strongly inhibited by phenylmethylsulfonyl fluoride, suggesting that the enzyme is a serine protease. The N-terminal amino acid sequence was Asp-Thr-Arg-Gln-Leu-Leu-Asn-Ala-Asn-Ser-Asp-Leu-Leu- Asn-Thr-Thr-Gly-Asn-Val-Thr-Gly-Leu-Thr-Gly-Ala-Phe-Asn-Gly-Gly-Asn. A search through the database for sequence homology yielded no significant match. The initial cleavage sites for oxidized insulin B-chain were found to be the Glu13-Ala14 and Phe24-Phe25 bonds. The result of the cleavage pattern of oxidized insulin B-chain suggests that CP-70 protease has a broader specificity than the other cold-active proteases against the peptide substrate.

Amino Acid Sequence↗
PubMed1998

Characteristics and clinical outcome of proximal-third gastric cancer.

BACKGROUND: It is generally accepted that the prognosis of patients with proximal gastric cancer (PGC) is worse than that of patients with more distal gastric cancer. STUDY DESIGN: The aim of this study was to compare the clinical features and outcomes of PGC with those of middle- and distal-third gastric cancers. A total of 646 primary gastric cancers was analyzed as a retrospective study. RESULTS: Proximal gastric cancer occurred in 21.8% of the 646 cancers analyzed, and approximately 21% of PGCs had esophageal invasion. The 5-year survival rate for patients with PGC was significantly lower than that of patients with more distal tumors. When the PGC group was divided into patients with esophageal invasion and without esophageal invasion, patients with esophageal invasion had significantly worse outcomes. When corrected for depth of invasion, lesions with esophageal invasion had significantly worse outcomes than those of other sites in T2 curative cancers. Proximal gastric cancer with esophageal invasion was characterized by a larger tumor, deeper penetration, and a higher incidence of lymph node metastasis compared with tumors in other sites, and in multivariate analysis of all curative cases, these variables were independent prognostic factors for survival. The frequency of positive proximal margins of PGC was higher than those of other sites. CONCLUSIONS: The relatively poor prognosis associated with PGC is mainly from advanced tumor stages of esophageal invasion. Early detection is the most important strategy to improve the survival of patients with PGC. In addition, aggressive lymph node dissection and chemotherapy for esophageal invasion should be considered even if the tumor invasion is moderate (T2 tumor), and a tumor-free margin is important.

Adult↗
PubMed1998

Staging of gastric cancer with endoscopic ultrasonography and endoscopic mucosal resection.

Since it was found that the gastrointestinal wall is visualized as a five-layered structure corresponding to the histological layers of the wall, endoscopic ultrasonography (EUS) has become recognized clinically as the most accurate method for diagnosing and assessing the local staging of gastric cancer. However, some problems have remained, including how to differentiate between cancer invasion and ulcer fibrosis, how to detect microinvasion, and how to recognize malignant lymph nodes. Using the pattern analysis for depressed-type gastric cancer, it is usually possible to distinguish between cancer invasion and ulcer fibrosis, except in cases of microinvasion into ulcer fibrosis or inadequate scanning. However, the sensitivity of EUS for evaluating metastatic lymph nodes is still problematic. Endoscopic mucosal resection (EMR) for early gastric cancer has been widely accepted as a standard treatment in Japan due to its minimal invasiveness. According to our data, the overall rate of radical resection was 68.3% (168 of 246), and 31.7% of the remaining patients additionally received laser treatment, surgery, or heater-probe treatment. There were no deaths owing to gastric cancer. Some lesions in which there was microinvasion of the submucosa were incorrectly diagnosed by EUS. It may be possible to solve this problem using three-dimensional EUS (3D-EUS) in the near future.

Endoscopy↗
PubMed1998

Expression of interferon receptor genes (IFNAR1 and IFNAR2 mRNA) in the liver may predict outcome after interferon therapy in patients with chronic genotype 2a or 2b hepatitis C virus infection.

Hepatitis C virus (HCV) genotype 2a or 2b is associated with a favorable outcome after interferon therapy. However, 19% to 33% of patients do not respond to therapy. We investigated whether interferon receptor gene (IFNAR1 and IFNAR2 mRNA) expression in the liver before interferon therapy predicts long-term response to therapy in patients with genotype 2a or 2b HCV infection. Twenty-seven patients who subsequently received interferon-alpha therapy underwent liver biopsies before interferon therapy. Hepatic IFNAR1 and IFNAR2 mRNA were determined using a reverse transcription-polymerase chain reaction assay. Twenty (74%) patients responded to interferon therapy, while the remaining seven (26%) patients were nonresponders. The expression rates of IFNAR1 and IFNAR2 mRNA in the liver were significantly higher in responders than nonresponders (p < 0.01, by chi-square test). The presence of either IFNAR1 or IFNAR2 mRNA predicted complete response to interferon treatment, with a positive predictive value of 100%. Multiple logistic regression analysis showed that IFNAR1 and/or IFNAR2 mRNA expression was the only significant predictor of the effectiveness of IFN therapy (p = 0.0002). We conclude that expression of interferon receptor genes in the liver is a useful index for predicting the long-term efficacy of interferon therapy in patients with chronic genotype 2a or 2b HCV infection.

Adult↗
PubMed1998

Identification and characterization of a cytotoxic T cell epitope of hepatitis C virus presented by HLA-B*3501 in acute hepatitis.

In order to clarify the role of cytotoxic T lymphocytes (CTL) in hepatitis C virus (HCV) infection, an HLA-B35-restricted cytotoxic T cell epitope of HCV was identified using a strategy called reverse immunogenetics. Twenty-eight of 53 HCV peptides carrying two anchor residues were selected as HLA-B*3501 binding peptides. These peptides were used to induce the specific cytotoxic T cells in peripheral blood lymphocytes from a patient with acute hepatitis C. Six HLA-B*3501 binding peptides induced the peptide-specific CTL. One (HPNIEEVAL) of five peptides was confirmed as the epitope by the specific T cell clones. A sequence identical to the epitope was detected in isolates of the virus from the patient and a strong CTL response to this epitope was observed in the acute phase of hepatitis C but not in the recovery phase. The specific CTL for this epitope were not detected in peripheral blood lymphocytes from patients with chronic hepatitis C. Together these results suggest that the CTL specific for this epitope have an important role in the elimination of the virus in the patient.

Acute Disease↗
PubMed1998

[Immunotoxicity of beryllium].

The lymphocyte transformation test and the macrophage migration inhibition test are quantitative methods invaluable for examination of beryllium (hereafter referred to as Be) effects on cell-mediated immunity. We recognized that the Be sensitizing ability was related to active as well as passive cell-mediated immunity in mice subcutaneously injected with Be once a week over a 6-week period. Be also affects B cells, and it increases the amount of immunoglobulins in sera. In the study of immunological health surveys of Be workers in a copper-beryllium casting factory, the serum complement titer tended to be lower in Be workers than in the controls. In mice, injected with Be once a week over a 12-week period, serum complement titers decreased. Correlation coefficients of the experimental parameters showed a significant negative correlation between the complement titers and the prothrombin time or the coagulation time for factor VII, using mice injected with 5 micrograms of Be. It was suggested that increases in the complement titers after Be administration may be induced by temporarily-activated plasma serin protease, which is a component of blood coagulation factor VII. The delta-aminolevulinic acid dehydratase and porphobilinogen deaminase activities were significantly elevated in the pregnant untreated group, compared with the nonpregnant mice (the control group). However, it was noted that these values in the pregnant mice injected with 50 micrograms of Be were almost the same as the values of the controls. It suggests that Be suppressed the expected pregnancy-induced increase in hematopoietic function. There are at least two risk factors induced in the effects of beryllium on organisms-exposure to the metal and inheritance of the genetic marker. It is necessary to reduce exposure, to give preventive education and to carry out periodic health examinations for the prevention of disease induced by Be.

Animals↗
PubMed1998

[Intra-arterial infusion of SMANCS for treatment of patients with hepatocellular carcinoma--adverse reactions and complications].

Although intra-arterial infusion of SMANCS has been demonstrated to be highly effective for treatment of patients with hepatocellular carcinoma, it is reported to cause critical adverse reactions and complications. We examined the adverse reactions of SMANCS on the hepatic artery in 78 patients with hepatocellular carcinoma, who were infused with SMANCS from right, left or proper hepatic artery at our hospital. SMANCS caused right hepatic artery occlusion in 15 patients (19%) and the average amount of infused SMANCS was 6.8 mg. The tumor volume in the artery occluded patients was smaller than that in the artery non-occluded patients. Then, the mechanism by which SMANCS caused arterial occlusion was its induction of arterial injuries by excess infusion. When SMANCS was infused to whole liver, it induced decreased hepatic functional reserve and liver atrophy, followed by delayed liver failure. Other adverse reactions were no different from those in patients infused with epirubicin-lipiodol emulsion.

Adult↗
PubMed1998

[Evaluation of hepatic artery occlusion after intra-arterial infusion of SMANCS in patients with hepatocellular carcinoma].

Although intra-arterial infusion of SMANCS is effective for the treatment of hepatocellular carcinoma, injury of the hepatic artery is occasionally encountered. We analyzed 78 patients with hepatocellular carcinoma who received intraarterial infusion of SMANCS. Twenty-seven patients who were treated by epirubicin were used as a control. Complete occlusion of the right hepatic artery was induced in 15 patients who received SMANCS infusion. The average number of administrations was 1.9 in the occluded group, 1.5 in the non-occluded group, and 1.6 in the epirubicin group. There was no statistically significant difference in the dose of drugs in a single session between the three groups (3.5 +/- 1.5 ml in the occluded group, 3.6 +/- 1.5 ml in the non-occluded group and 4.2 +/- 1.2 ml in the epirubicin group), and there was no statistically significant difference in total dose between the three groups (6.8 +/- 2.6 ml in the occluded group, 5.5 +/- 3.6 ml in the non-occluded group and 6.8 +/- 4.3 ml in the epirubicin group). However, total dose per tumor volume was significantly larger in the occluded group (1.1 +/- 1.0 cm3) than in the non-occluded group (0.5 +/- 0.5 cm3) (p < 0.05). Excess infusion of SMANCS for small hepatocellular carcinomas appears to be an important factor in vascular injury.

Aged↗
PubMed1997

Alteration of reticuloendothelial phagocytic function and tumor necrosis factor-alpha production after total hepatic ischemia.

BACKGROUND: This study was conducted to determine whether the duration of total hepatic ischemia influences reticuloendothelial phagocytic activity and tumor necrosis factor (TNF)-alpha production after reperfusion. METHODS: Male rats pretreated with either normal saline (NS group) or gadolinium chloride (7 mg/kg) for 2 days to inhibit Kupffer cell function (GC group) were subjected to 30, 60, or 90 min of total hepatic ischemia. RESULTS: The animals tolerated hepatic ischemia well for 30 and 60 min. Although the 7-day survival rate of the NS group decreased to 28% after 90 min of hepatic ischemia, that of the GC group improved significantly to 68% (P<0.01). In the NS group, plasma alanine transaminase and TNF-alpha levels after reperfusion increased with the length of hepatic ischemia. The phagocytic index (PI) after 60 min of reperfusion following 90 min of hepatic ischemia showed significant depression compared with the preischemic level and the value after 30 or 60 min of ischemia. The GC group had significantly lower plasma alanine transaminase and TNF-alpha levels as well as significantly less polymorphonuclear leukocyte infiltration in the liver compared with the NS group. The preischemic PI was significantly inhibited in the GC group when compared with that in the NS group, but PI in the GC group did not change significantly after reperfusion, irrespective of the ischemic time. CONCLUSIONS: This study demonstrated that warm ischemia of up to 60 min is tolerable for normal rat liver without a detrimental effect on phagocytic activity. Modulation of Kupffer cell function may have the potential to prevent reperfusion injury after hepatic ischemia, which may allow safe prolongation of the ischemic time.

Alanine Transaminase↗
PubMed1997

Simultaneous topographic and fluorescence imagings of recombinant bacterial cells containing a green fluorescent protein gene detected by a scanning near-field optical/atomic force microscope.

A scanning near-field optical/atomic force microscope (SNOAM) system was applied for simultaneous topographic and fluorescence imaging of biological samples in air and liquid. The SNOAM uses a bent optical fiber simultaneously as a dynamic mode atomic force microscopy cantilever and as a scanning near-field optical microscopy probe. Optical resolution of this system was about 50-100 nm in fluorescence mode for fluorescent latex beads on a quartz glass plate. Green fluorescent protein (GFP) is a convenient indicator of transformation and should allow cells to be separated by fluorescence-activated cell sorting. The gene coding to GFP was cloned in recombinant Escherichia coli. The SNOAM system used 458- or 488-nm irradiation from a multiline Ar ion laser for excitation of GFP, since a native GFP has been known to give a maximum at 395 nm and a broad absorption spectrum until 500 nm. Topographic and fluorescence images of recombinant E. coli were obtained simultaneously with a high spatial resolution which was apparently better than that of a conventional confocal microscope. A nanoscopic GFP fluorescence spectrum was obtained by positioning the optical fiber probe above the bright area of the E. coli cells. Comparing topographic and fluorescence images, it can be seen that individual E. coli cells expressed different fluorescence intensities. Fluorescence obtained by SNOAM indicated that GFP oxidation possibly occurred near the cell surface. A SNOAM system also indicated the possibility of precise imaging of native cells in liquid.

Escherichia coli↗
PubMed1997

Phosphorylation of the Sendai virus M protein is not essential for virus replication either in vitro or in vivo.

A large proportion of intracellular Sendai virus (SeV) M proteins is phosphorylated, but in mature virions the M protein is not phosphorylated or dephosphorylated. Phosphorylated M protein in cells is bound to the cytoskeletal components more firmly than unphosphorylated M protein. Thus it has been hypothesized that M protein phosphorylation plays an important role in the virus life cycle, especially in the step of maturation. Here, a transient expression-mutation experiment of the M gene demonstrated that a change of the Ser residue at the 70th position from the N-terminus to Ala (S70A) totally abolished M protein phosphorylation, strongly suggesting that this residue is phosphorylated. The mutated M gene was then placed in the corresponding region in the cDNA plasmid which generates a full-length antigenome SeV RNA, and a mutant SeV M-S70A was successfully recovered from the cDNA. This mutant virus was indeed defective in M protein phosphorylation but did not differ at all from the wild-type SeV recovered from the parental cDNA either in the replication kinetics and plaque morphology in cultured cells or in in vivo replication and pathogenicity for mice. We thus concluded that no phosphorylation of the M protein was required for SeV replication either in vitro or in vivo.

Animals↗