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Biomedical subjects

T Tsuji

Publications and source records attributed to T Tsuji.

At least 685 records · Page 38Linked to original sources
PubMed1993

Synthesis and structure-activity relationships of 7-(3'-amino-4'-methoxypyrrolidin-1'-yl)-1-cyclopropyl-6,8-difluoro-1,4- dihydro-4-oxoquinoline-3-carboxylic acids.

A new series of quinolone derivatives 3a--1 bearing 3-amino-4-methoxypyrrolidines of different configurations and chirality were synthesized and their antibacterial activities as well as some of their toxicological properties were examined. As predicted by our previous quantitative structure-activity relationships (QSAR) analysis of C-7 heterocyclic amine substituted quinolonecarboxylic acid antibacterial agents, these pyrrolidine derivatives showed higher in vitro and in vivo antibacterial activities against both gram-positive and gram-negative bacteria than the analogs bearing various 3-substituted azetidines. Furthermore, the amino and methoxy substituent groups on the pyrrolidine ring exhibited strong configurational and chiral effects on the in vitro and in vivo antibacterial activities of these compounds: (1) cis compounds showed higher antibacterial activities against most of the pathogens examined; (2) N-methylation of the 3-amino group on the pyrrolidine ring lowered in vitro but not in vivo antibacterial activities, particularly leading to superior in vivo anti-pseudomonal activity; (3) the (3'S,4'R)-derivative showed substantially higher activity that the (3'R,4'S)-one. These findings led to the selection of compound 3k for further evaluation as it possessed the highest in vivo antibacterial activity and no cytotoxicity.

Anti-Bacterial Agents↗
PubMed1993

Amino acids and peptides. XVII. Synthesis of peptides related to N-terminal portion of fibrin alpha-chain and their inhibitory effect on fibrinogen/thrombin clotting.

Various peptides related to N-terminal portion of fibrin alpha-chain were synthesized by the solution method and the solid-phase method, and their inhibitory effect on fibrinogen/thrombin clotting was examined. Extension of peptide chain from N-terminal tripeptide decreased the inhibitory effect. The most potent effect was shown by N-terminal decapeptide analog, H-Gly-Pro-Arg-Pro-Pro-Glu-Arg-His-Gln-Ser-NH2.

Amino Acid Sequence↗
PubMed1993

Auto-antibody against adenine nucleotide translocator in dilated cardiomyopathy and myocarditis--incidence and relation to cardiac function and morphology.

Using an enzyme-linked immunosorbent assay, we measured anti-adenine nucleotide translocater (ANT) antibody in control subjects and in patients with dilated cardiomyopathy (DCM), myocarditis, and other heart disease. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and immunoabsorption tests confirmed accurate purification of the ANT protein and correct measurement of anti-ANT auto-antibody. Anti-ANT antibody was detected in 6 of 37 cases (16%) of DCM and in 5 of 12 cases (42%) of myocarditis. This antibody was not positive in other heart diseases or in apparently healthy controls. There were no differences between anti-ANT autoantibody-positive and -negative DCM or myocarditis patients in any of the cardiac parameters examined (left ventricular ejection fraction, LVEF; left ventricular end-diastolic dimension, LVDd; and cardiothoracic ratio, CTR). Moreover, in patients who were positive for anti-ANT auto-antibody, no positive correlations were found between the parameters and anti-ANT antibody titers in either DCM or myocarditis. Although these results indicate that the detection of anti-ANT antibody was achieved at a high specificity and could have certain diagnostic value in DCM and myocarditis, there was no statistically significant relationship between the cardiac parameters (LVEF, LVDd, and CTR) and anti-ANT antibody titers in either DCM or myocarditis. Some compensatory mechanism of ventricular function may mask the effects of the anti-ANT auto-antibody or alternatively, this auto-antibody may have mimic effects on the pathogenesis and/or progression of DCM and myocarditis.

Adult↗
PubMed1993

Acute left main coronary artery obstruction with myocardial infarction--reperfusion strategies, and the clinical and angiographic outcome.

We studied the clinical and angiographic outcomes in 8 patients with acute left main coronary artery obstruction. Intracoronary thrombolysis with 1.2 x 10(5) units of urokinase was performed in 3 patients during preparation for percutaneous transluminal coronary angioplasty (PTCA), and failed in all 3 cases. In 2 patients, the left main coronary artery was recanalized by intracoronary thrombolysis with 3.6 and 4.8 x 10(5) units of urokinase, respectively. PTCA was attempted either before or after intracoronary thrombolysis in 5 patients and achieved reperfusion in all 5 cases. However, 2 of the 8 patients had persistent high-grade residual stenosis 69% and 89% luminal reduction, respectively. Emergency coronary artery bypass grafting was successfully performed in these 2 patients, and both are currently alive. Although intraaortic balloon counterpulsation was performed in all 8 patients, 2 died acutely from pump failure in the catheterization laboratory. One patient died later due to congestive heart failure. The factors favoring survival were right coronary artery dominance and a well-developed collateral circulation. Our findings suggest that PTCA is a useful strategy for reperfusion following acute left main coronary artery occlusion. When PTCA cannot achieve sufficient revascularization, emergency coronary artery bypass grafting should be performed. To control pump failure, intraaortic balloon counterpulsation is insufficient in some cases and more aggressive measures may be required.

Aged↗
PubMed1993

Stimulation of nerve growth factor synthesis and secretion by fellutamide A in vitro.

Fellutamide A, a tripeptide derivative from Penicillium fellutanum was found to be a potent enhancer of nerve growth factor (NGF) synthesis and secretion in vitro. This compound enhanced production of NGF in L-M cells, rat brain cells, and rat glial cells. The mode of action of this compound was suggested to be different from that of a known NGF inducer, epinephrine, as inducing activities of fellutamide A and epinephrine were additive when they were admixed at the concentration which gave saturation in its respective activity. Furthermore, fellutamide A but not epinephrine induced production of NGF in the rat brain cells. NGF-inducing activity of several tripeptides and other compounds related to fellutamide A was examined.

Amino Acid Sequence↗
PubMed1993

Analysis of asparagine-linked oligosaccharides by sequential lectin-affinity chromatography.

Various immobilized lectins can be successfully used for fractionation and for structural studies of asparagine-linked sugar chains of glycoproteins (see Note 9). This method needs < 10 ng of a radiolabeled oligosaccharide prepared from a glycoprotein by hydrazinolysis or by digestion with endo-beta-N-acetylglucosaminidases. The fractionation and the structural assessment through the use of immobilized lectins make the subsequent structural studies much easier.

Animals↗
PubMed1993

Recombinant mouse cytochromes P1-450 and P3-450: enzymatic characterization of the hemoprotein expressed in human cells infected with recombinant vaccinia virus.

We expressed mouse cytochrome P1-450 and P3-450 using recombinant vaccinia virus gene expression system in HeLa cells that were devoid of significant basal levels of P-450. HeLa cells were infected with the recombinant vaccinia virus containing either mouse cytochrome P1-450 or P3-450 cDNA, and the cell lysates were analyzed for the kinetics of P-450 enzyme activity and protein expression at the same time. 7-Ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activities were measured as an expression of the cytochrome P-450 enzyme activities. Both cell lines began to express these enzyme activities as early as 12h after infection. The activities increased linearly up to the 24 h time point, and were kept for 36 h. Western immunoblot analysis showed that these cytochrome P-450 proteins were detected at 16 h and reached maximum quantity at 24 h after infection. These data showed a good correlation between cytochrome P-450 enzyme activity and protein concentration throughout the process of P-450 gene expression by vaccinia virus vector, suggesting a complete formation of cytochrome P-450 holoenzyme from the early stage of the protein expression.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1993

Autoimmune responses as assessed by hypergammaglobulinemia and the presence of autoantibodies in patients with chronic hepatitis C.

We investigated autoimmunity, as assessed by hypergammaglobulinemia and the presence of autoantibodies including anti-nuclear antibodies (ANA) and anti-liver membrane antibodies (LMA), in 149 patients with chronic hepatitis C, 55 patients with chronic hepatitis B and 11 patients with autoimmune hepatitis. There was no significant difference in the incidence of these autoantibodies between chronic hepatitis C and chronic hepatitis B. Nine patients with chronic hepatitis C satisfied the serological criteria of autoimmune hepatitis (ANA positive and gammaglobulin or serum IgG greater than 2500 mg/dl), but none of the patients with chronic hepatitis B met the criteria. This suggests that autoimmunity is greater in chronic hepatitis C than in chronic hepatitis B. Of the 9 patients with chronic hepatitis C, all 4 patients tested for human leukocyte antigen (HLA) phenotype had HLA-DR4, which is known to be associated with autoimmune hepatitis in Japanese patients. We believe that hepatitis C virus (HCV) infection enhances the initiation and perpetuation of autoimmunity in susceptible individuals.

Adult↗
PubMed1993

Detection of negative strand RNA of hepatitis C virus in infected liver and serum.

The negative strand RNA of hepatitis C virus, supposed to be a replicative intermediate of the virus appears to indicate viral replication. In this study, we detected the negative strand RNA by using reverse transcription-polymerase chain reaction with RNase A digestion to degrade the remaining positive strand genomic sequence of the virus after complementary DNA (cDNA) synthesis. In vitro transcribed positive-stranded mutant RNA was not detected by this method. Sample sera and liver tissues of 16 patients with chronic hepatitis C virus infection (liver fibrosis, 1; chronic hepatitis, 13; liver cirrhosis, 2) were analysed for negative strand RNA of hepatitis C virus. The negative strand RNA sequence was detected in 15 (93%) of 16 liver tissues and in 11 (78%) of 14 sera. The study demonstrated that negative strand RNA of hepatitis C virus in serum and liver tissue could be specifically detected.

Adult↗
PubMed1993

Loss of ICG uptake in the process of rat hepatocarcinogenesis correlates to the disappearance of glutathione-S-transferase alpha subunit.

Reduced indocyanine green (ICG) uptake is one of the functional changes of human hepatocellular carcinoma (HCC). To clarify the mechanisms of loss of ICG uptake, and determine which subunit of glutathione-S-transferase (GST), alpha or pi, plays a role in ICG transport in hepatocytes, an experimental HCC model was developed that used nodules induced by 2-acetylamino-fluorene (2-AAF) administration. Many of the ICG stained nodules, which consisted of benign and borderline lesions, were GST-alpha positive. However, the percentage of GST-alpha positive cells tended to decrease according to the disappearance of ICG staining in the process of hepatocarcinogenesis. HCCs unstained by ICG were also GST-alpha negative. GST-pi, not detected in normal rat hepatocytes, appeared in an earlier stage of hepatocarcinogenesis before the disappearance of GST-alpha, and was not observed in HCCs. No significant relationship between ICG staining and GST-pi was recognized. These results suggest that GST-alpha synthesis is disturbed in the process of hepatocarcinogenesis and results in loss of ICG uptake in HCCs, and also indicate that GST-pi may be useful for early diagnosis of preneoplastic hepatocytes showing no roles in ICG transport.

Animals↗
PubMed1993

Survival simulation of hepatocellular carcinoma derived from follow-up studies of 450 patients.

A simulation model to predict the survival probability of individual patients with hepatocellular carcinoma (HCC) after therapy was derived from the results of various therapies and follow-up studies of 450 HCC patients. Twenty-two prognostically important variables were analyzed by Cox's proportional hazards model. The 9 significant variables that were extracted were used to build the simulation. In this model, S(t), the expected estimated survival rate for individual patient at time t (month), is calculated by the following equation: S(t) = (exp (-0.03655t) (exp [0.9479 ([portal vein invasion]-0.222) + 0.3846 ([tumor number]-2.00) + 0.2578 ([tumor size]-3.231) + 0.0742 ([loge AFP]-5.647) + 0.8184 ([metastasis]-0.036) + 0.2810 ([Child's class]-1.689)-0.7088 ([transcatheter arterial embolization]-0.578)-0.9746 ([percutaneous ethanol injection]-0.153)-0.5377 ([hepatectomy]-0.109)]) The validity of the model was assessed using a split-sample technique. This paper does not discuss the superiority or inferiority of the therapies, because some selection bias for prognostic factors among the therapies can not be completely excluded. But this model is proposed as a practical model to predict the survival of patients with HCC.

Carcinoma, Hepatocellular↗
PubMed1993

Malignant pheochromocytoma with hepatic metastasis diagnosed 20 years after resection of the primary adrenal lesion.

A 59-year-old woman developed multiple hepatic tumors 20 years after resection of pheochromocytoma of the left adrenal gland. Thin-needle aspiration biopsy of the tumor at segment 2 of the liver under ultrasound control showed histology compatible to pheochromocytoma. Then, on the basis of the diagnosis of hepatic metastasis of malignant pheochromocytoma, transcatheter arterial embolization (TAE) was performed for the purpose of the treatment of hepatic metastasis. After TAE, the size of the hepatic metastatic lesions was decreased. The present case suggests the necessity of long-term follow-up in pheochromocytoma cases.

Aclarubicin↗
PubMed1993

Evaluation of antibody against AR142, a synthetic peptide derived from the core sequence of hepatitis C virus, in the diagnosis of non-A, non-B chronic liver disease.

We evaluated serum anti-hepatitis C virus (HCV) using a synthetic peptide (AR142) which includes an epitope in the core region of HCV. The incidence of anti-AR142 in 98 patients with type non-A, non-B chronic liver diseases (NANB-CLD) was 89.8%, while all the 28 patients with non-type C chronic liver diseases were negative for anti-AR142. Among 98 NANB-CLD patients, 74 were positive for both anti-AR142 and anti-C100-3, 23 showed discordant results, and one was positive for neither. Eighty-one NANB-CLD patients underwent reverse transcription-polymerase chain reaction assay to detect viremia and 76 (93.8%) had a detectable level of HCV-RNA. Titers of anti-AR142 were not different among groups of different disease activities, genotypes of HCV, nor amount of serum HCV-RNA. These observations suggest that anti-AR142 could be a useful marker for chronic HCV infection.

Adult↗
PubMed1993

Immunological mechanism of chronic liver injury in viral hepatitis.

Chronic hepatitis B and chronic hepatitis C centering on immunohistochemical studies of the liver were investigated as possible mechanisms of the chronicity of viral hepatitis. Although liver cell injury was presumed to be caused by CTL in both chronic hepatitis B and C, other mechanisms of cell injury were also presumed with chronic hepatitis, type C, including autoimmune mechanisms.

Antigens, Viral↗
PubMed1993

Production of alpha-fetoprotein by human submandibular gland.

Alpha-fetoprotein (AFP) is a 590 amino acid polypeptide that was initially defined as an embryonal serum globulin. The yolk sac endoderm, fetal liver and fetal gut were shown to be the main sites of AFP synthesis in the embryo (Gitlin and Boesman, J. Clin. Invest. 46: 1010-1016, 1967). AFP synthesis is still continued in human adults (Ruoslahti and Seppala, Int. J. Cancer 8: 374-383, 1971) although the physiological level of serum AFP is lower than 10 ng/ml. AFP was also demonstrated in certain tumors and in various diseases or conditions such as yolk sac tumor, hepatoma, hepatoblastoma, acute and chronic liver cirrhosis, pregnancy and so on (Abelev, Adv. Cancer Res. 14: 295-358, 1971; Ruoslahti and Seppala, Cancer Res. 29: 275-346, 1979). Salivary glands have not been implicated in AFP synthesis. We investigated the expression of AFP in normal human salivary glands by immunohistochemistry with a monoclonal antibody against AFP, and documented immunoreactivity in intercalated and striated ducts of adult human submandibular glands.

Adult↗
PubMed1993

Prolongation of survival for carcinoma at the hepatic duct confluence.

BACKGROUND: Because of poor long-term results in resection for carcinoma at the hepatic duct confluence, we have adopted a more aggressive approach. METHODS: The records of 46 patients with carcinoma of the hepatic duct confluence were reviewed. Twenty-four patients underwent hepatic resection and 10 underwent local resection. The remaining 12 patients had unresectable lesions and received palliative treatment. Out of 24 patients who underwent hepatic resection, 17 underwent combined resection of the caudate lobe. Five patients who underwent hepatic resection and three patients who underwent local resection received intraoperative radiotherapy in a dose of 30 Gy of electron beam. Postoperative radiotherapy with a total dose of 50 Gy of external electron beam was performed for five patients who underwent nonradical hepatic resection and one patient who underwent nonradical local resection. RESULTS: None of the 10 patients who underwent local resection and only 1 (4.2%) of 24 patients who underwent hepatic resection died in the hospital. Among patients who underwent hepatic resection, the 1-, 3-, and 5-year survival rates were 62%, 37%, and 25%, respectively, whereas the respective survival rates in the group that underwent local resection were 50%, 20%, and 20%. The 1-, 3-, and 5-year survival rates for patients who underwent combined caudate lobectomy were 69.7%, 53.4%, and 23%, respectively, compared with 57.1%, 26%, and 14.3% for those who did not. The median survival time for patients who received radiotherapy after nonradical resection was 17 months, compared with 5 months for those who did not. CONCLUSIONS: These results suggest that major hepatic resection combined with caudate lobectomy should be performed for carcinoma of the heptic duct confluence. Postoperative radiotherapy after nonradical resection may be effective in prolonging survival.

Adult↗
PubMed1993

[Leukocyte activity and occurrence of tissue injury by G-CSF].

G-CSF (granulocyte-colony stimulating factor) is one of the cytokines which increase and activate neutrophils. These effects have been confirmed by a lot of clinical studies. Although only few side effects have been reported so far, we saw a patient with hypertension, facial edema, and severe headache after G-CSF administration. We have measured the sticking strength of leukocytes to the walls of narrow pores in modified Nuclepore filtration method of Kikuchi, in various clinical situations, and we have denoted the pore filtration time as the rheological activity of leukocytes (RAL). In this study, we tried to measure RALs of patients after G-CSF administration (60-100 micrograms) and to compare them with those of non-treated normal individuals. We also checked serum levels of granulocyte elastase in the patients. In the static state (in which neutrophils were not stimulated), RALs of the patients were 8.0 +/- 1.5sec. [N = 8], and those of the controls were 3.8 +/- 1.6sec. [N = 21] (p < 0.001). In the activated state (in which neutrophils were stimulated by formyl-methionyl-leucyl-phenylalanine), PALs of patients were quite high, i.e. those of the patients and controls were 592 +/- 322sec. and 69 +/- 62sec., respectively (p < 0.001). In all cases given G-CSF, the serum levels of granulocyte elastase were above the normal range. In view of our results, we it is possible that highly activated leukocytes would injure tissue and then induce organ failure and several symptoms, as in this study.

Adult↗