The role of platelet activating factor (PAF) in the pathogenesis of gastric ulcers.
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Animals↗
Biomedical subjects
Y Sameshima
Publications and source records attributed to Y Sameshima.
Prognosis of unresectable hepatocellular carcinoma: an evaluation based on multivariate analysis of 90 cases.
A multivariate analysis of data from 90 patients with unresectable hepatocellular carcinoma was performed using Cox's regression model to identify factors possibly affecting their prognoses. Thirty-one patients underwent arterial anticancer chemotherapy, and the remaining 59 patients received transcatheter arterial embolization with anticancer agents. Four of 27 variables tested for all the patients (i.e., encapsulation [p less than 0.05], gross appearance of hepatocellular carcinoma [p less than 0.01], clinical stage [p less than 0.01] and therapy [p less than 0.01]) were found to be prognostically significant. Five of 27 variables tested were prognostically significant for the transcatheter arterial embolization group; they were an extension rate of hepatocellular carcinoma (p less than 0.01), encapsulation (p less than 0.01), alpha-fetoprotein (p less than 0.01), prothrombin time (p less than 0.01) and serum sodium (p less than 0.01). Regression equations were used to describe a prognostic index. A prognostic index was defined as the regression equation derived from the results of a total of 90 patients; PI-1 = eY, where PI-1 = prognostic index 1 Y = 1.549 (gross appearance of hepatocellular carcinoma - 1.344) + 0.778 (encapsulation - 1.622) + 0.818 (clinical stage - 1.800) + 1.760 (therapy - 1.344) and prognostic index 2, the regression equation derived from the results of the transcatheter arterial embolization group of patients; PI-2 = eY, where PI-2 = prognostic index 2 Y = 1.210 (extension rate of hepatocellular carcinoma - 1.576) + 1.179 (encapsulation - 1.475) + 0.0001277 (alpha-fetoprotein - 1420.792) -0.039 (prothrombin time - 72.237) - 0.214 (serum sodium - 138.427).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Tumor suppressor genes involved in metastasis of lung and colorectal carcinomas.
Inactivation of tumor suppressor genes is now believed to play an important role in various progression stages of human cancers. To clarify the possible involvement of tumor suppressor gene inactivation in the acquisition of metastatic potential in lung and colorectal carcinoma cells, we examined various genetic alterations in both primary tumors and metastases obtained from patients with lung and colorectal carcinomas. In lung carcinoma, loss of heterozygosity on chromosomes 3p, 13q, and 17p is a common genetic alteration, and both RB and p53 genes are inactivated as a result of chromosome 13q and 17p losses. In some cases, allelic loss on chromosome 11p and amplification of myc family oncogenes occur during tumor progression. In colorectal carcinoma, p53 and DCC alterations were detected in 100% of metastases, and sequential accumulation of allelic losses on chromosomes 13q, 14q, and 18q in the process of metastasis was observed. These results indicate that a subset of tumor suppressor genes is involved in metastasis of lung and colorectal carcinomas.
Colorectal Neoplasms↗
Point mutation of the p53 gene resulting in splicing inhibition in small cell lung carcinoma.
The p53 gene is functionally inactivated mostly by point mutations resulting in amino acid substitutions in a wide variety of human cancers. We found a novel mutation of the p53 gene in a small cell lung carcinoma cell line, Lu-143. One of the allelic p53 genes was lost accompanied by loss of heterozygosity for chromosome 17. In the remaining allelic p53 gene, there was a single-base substitution of G to T at position 1 within the splice donor site of intron 7, and the mutated intron was not spliced out during the mRNA maturation process. As a result of this mutation, larger sized p53 mRNA was expressed and no p53 specific protein was detected in this cell line. These results suggest that mutations causing splicing abnormalities are one of the molecular mechanisms for the p53 gene inactivation in human cancer.
Alleles↗
Characterization of ferrochelatase in kidney and erythroleukemia cells.
Ferrochelatase from bovine kidney mitochondria has been purified 1600-fold with a 6.5% yield, exhibiting a specific activity of 490 nmol mesoheme formed/mg of protein per min. The Km values for mesoporphyrin IX and protoporphyrin IX with iron were 12.5 and 12.7 microM, respectively. The Km values for iron and zinc with mesoporphyrin IX were 3.51 and 3.17 microM, respectively. The purified enzyme showed a single band with an apparent molecular mass of 42,000 daltons (42 kDa) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The rabbit antibody against the purified enzyme markedly inhibited activities of the enzyme from both the kidney and liver. Immunoblot analysis showed that the antibody reacted with the renal as well as the hepatic enzymes showing the same molecular weight. Peptide mapping with trypsin or alpha-chymotrypsin showed that digested peptides of renal enzyme were similar to those of hepatic enzyme. Ferrochelatase activity in mouse erythroleukemia (MEL) cells increased in parallel with an increase of heme synthesis by treatment with dimethylsulfoxide. Using immunoblotting techniques, the amount of the enzyme in the MEL cells has been shown to increase by the induction, showing a molecular mass of 41 kDa which was the same as that of the mouse hepatic enzyme. Comparative structural analysis of the enzyme of MEL cells and that of mouse liver by peptide mapping showed that the partial digestive peptides of both enzymes exhibited a similar pattern. These results strongly suggest that ferrochelatase in kidney, liver and erythroid cells can be of one type.
Animals↗
Depression of drug metabolizing activity in the human liver by interferon-alpha.
The depressant effect of interferon-alpha on drug metabolizing activity in the liver has been investigated in 12 patients with chronic active hepatitis B. 7-methoxy-coumarin (7-MC) O-demethylase and 7-ethoxycoumarin (7-EC) O-deethylase, in specimens obtained by liver biopsy, were measured before and after interferon treatment. 7-MC and 7-EC O-dealkylase activity were significantly reduced after interferon treatment, from 13.4 to 9.24 nmol.g-1 liver.min-1, and from 3.22 to 2.16 nmol.g-1 liver.min-1, respectively. The magnitude of the fall varied widely between individual patients. The study provides the first direct evidence that interferon-alpha can impair the activity of drug metabolizing enzymes in the human liver.
7-Alkoxycoumarin O-Dealkylase↗
Gastric hemodynamic disturbance induced by hemorrhagic shock in rats. Role of platelet-activating factor.
The role of platelet-activating factor (PAF) in the induction of rat gastric mucosal damage by ischemia-reperfusion was examined with reference to hemodynamic characteristics. Gastric mucosal hemodynamics was measured continuously, using laser-Doppler flowmetry and reflectance spectrophotometry. Not only gastric mucosal damage but also characteristic hemodynamic change--that is, ischemia with congestion--was observed in the PAF infusion and reperfusion periods of the ischemia-reperfusion model. CV-6209, a specific PAF antagonist, significantly alleviated gastric mucosal damage and hemodynamic disturbance induced by ischemia-reperfusion. These results strongly suggest that PAF is a potent mediator of gastric mucosal damage during reperfusion in the ischemia-reperfusion model.
Animals↗
Profiles of plasma amino acids in fasted patients with various liver diseases.
We examined the level of plasma amino acids, glucose, immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) of patients in the fasted state with acute hepatitis in the actual acute stage (AHa), acute hepatitis in the convalescent stage (AHc), chronic active hepatitis (CAH), chronic persistent hepatitis (CPH) and liver cirrhosis (LC). In AHa patients, the plasma glucose (FPG), plasma alanine (Ala), tryptophan (Trp) and histidine (His) levels were significantly lower and plasma cystine (Cys) level significantly higher than the control levels. This however, was not the case in the other patients. The glutamic acid (Glu) concentration was significantly higher in AHa (p less than 0.02), CAH (p less than 0.001) and CPH (p less than 0.001) and the tyrosine (Tyr) concentration was significantly higher in AHa (p less than 0.02), CPH (p less than 0.001), CAH (p less than 0.001) and LC (p less than 0.001) than they were in the controls. The lysine (Lys) concentration was significantly raised in the AHa (p less than 0.02) and CPH (p less than 0.05) cases. The IRG level was significantly higher in AHa (p less than 0.001), in AHc (p less than 0.01) and LC (p less than 0.01). Valine (Val) showed a significant decrease in concentration in AHa (p less than 0.01) and LC (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Use of a specific monoclonal antibody to detect Mallory bodies in liver disease.
Mallory bodies (MBs), which are common in alcoholic hepatitis, primary biliary cirrhosis and liver disease associated with Type II diabetes mellitus, are often difficult to find on liver biopsy specimens or to predict from clinical or biochemical studies. Immunofluorescence studies with anti-NMB-1, a Mallory body-specific monoclonal antibody, indicate that this is a sensitive method for recognizing Mallory bodies in cryostat sections of liver from griseofulvin-treated mice or patients with liver disease. Validity of the leukocyte migration test, which facilitates detection and monitoring of patients who harbor Mallory bodies, is confirmed by pretreatment of Mallory bodies with anti-NMB-1. Prevention of Mallory body-induced migration inhibition by addition of anti-NMB-1 indicates that this effect is not due to inactivation of leukocytes by a Mallory body contaminant. Anti-NMB-1, developed using standard hybridoma techniques, does not react with normal hepatocytes or other cells. Investigations with SDS polyacrylamide gel electrophoresis and western blotting reveal that it exhibits binding with 62, 55, 42 kd peptides, and four other bands in the range from 40 to 30 kd from the Mallory bodies. The NMB-1 epitope which facilitates morphologic and clinical detection of Mallory bodies is distinct from cytokeratin and appears to be responsible for its immunogenicity.
Animals↗
A case of hilar cholangiocarcinoma treated by microwave tissue coagulation therapy via percutaneous transhepatic choledochoscopy.
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Adenoma, Bile Duct↗
[A case of calcified gastric cancer--review of Japanese literature].
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Adenocarcinoma, Mucinous↗
Variable mutations of the RB gene in small-cell lung carcinoma.
Loss of heterozygosity for chromosome 13q including the RB locus is a common genetic alteration in small-cell lung carcinoma (SCLC) as well as in retinoblastoma. We examined the RB cDNA sequences of exon 13 to 18 and exon 19 to 23 in 9 SCLC cell lines to detect mutations which cause inactivation of the remaining allele of the RB gene. Internal deletions of RB cDNA were observed in 3 of the 9 SCLC cell lines. In the Lu-24 cell line, a 114 base pairs (bp) deletion corresponding to exon 22 was due to abnormal splicing, which probably resulted from a two-base mutation within genomic exon 22, and aberrant 105 kilodaltons RB protein was detected by immunoprecipitation analysis. A base pair deletion within exon 20 in the Lu-135 cell line and a 1 bp deletion within exon 23 in the Lu-141 cell line were due to the deletions of the corresponding genomic DNA, and each deletion resulted in formation of a premature termination codon. These results indicate that both alleles of the RB genes are inactivated in SCLC by several different mechanisms, including small deletion, mutation and chromosomal loss.
Alleles↗
[A case of liver cystadenoma--significance of tumor marker level of the cyst fluid in differentiating pathological nature].
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Adult↗
Occurrence of platelet-activating factor (PAF) in normal rat stomach and alteration of PAF level by water immersion stress.
We detected platelet-activating substance in gastrointestinal areas, which was confirmed to be platelet-activating factor (PAF) on the basis of the following findings: 1) it comigrated with authentic PAF on thin-layer chromatography; 2) it did not aggregate PAF-desensitized platelets; and 3) its activity was completely antagonized by the receptor antagonists CV3988 and L-652,731. The level of PAF was determined with a bioassay method based on the release of [3H]serotonin from washed rabbit platelets. In the normal rat stomach, the level of PAF was high in the antrum (940 +/- 200 nmol PAF/mol phosphorus of original phospholipids), especially in the antral mucosa (1801 +/- 426 nmol/mol phosphorus of original phospholipids). The stomach PAF level was significantly altered by water immersion stress. Stress for a period of 1 h was associated with a decrease in the antral PAF level to 39 +/- 7% of that of untreated controls. This low PAF level persisted during stress. On the other hand, in the corpus, stress for periods of 1 and 3 h was associated with decreases in the PAF content, and further stress (7 h) resulted in restoration of the PAF level to normal. Furthermore, 7 h of stress was associated with distinct hemorrhagic lesions, which were prevented by CV3988 infused i.v. before the stress. This is the first report of an association between a decrease of the endogenous PAF level in animal tissues and tissue damage.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Comparison of the effects of various inducers on 7-alkoxycoumarin O-dealkylase activities in liver microsomes.
The effects of six inducers and malotilate on 7-alkoxycoumarin O-dealkylase activities in rat liver microsomes were examined. Phenobarbital (PB) (100 mg/kg) was administered intraperitoneally to rats for 6 days; 3-methylcholanthrene (3-MC) (40 mg/kg), beta-naphthoflavone (beta-NF) (40 mg/kg), isosafrole (150 mg/kg) and polychlorinated biphenyls (PCB) (100 mg/kg) were administered intraperitoneally for 3 days; isoniazid (INH) (50 mg/kg) was administered intraperitoneally for 10 days; and malotilate (500 mg/kg) was administered orally for 3 days. The O-dealkylase activities toward 7-methoxycoumarin (7-MC), 7-ethoxycoumarin (7-EC) and 7-propoxycoumarin (7-PC) were examined 24 hr after the final administration of the drugs. The ratios of 7-EC O-deethylase and 7-PC O-depropylase to 7-MC O-demethylase activity in the control and six inducer-treated groups were compared. The ratios in the groups treated with the six compounds, each of which induces a different form(s) of cytochrome P-450 (P-450), were clearly different from each other. Therefore, the measurement of 7-alkoxycoumarin O-dealkylase activities should be extremely useful for the routine determination of the molecular species of P-450. On the other hand, the ratio in the malotilate-treated group was different from that in any other inducer-treated group, so that there might be a possibility that malotilate induced a form(s) of P-450 that is different from any of the already known species.
7-Alkoxycoumarin O-Dealkylase↗
Serum platelet-activating factor acetylhydrolase activity in rats with gastric ulcers induced by water-immersion stress.
Platelet-activating factor (PAF) acetylhydrolase is an enzyme which hydrolyzes PAF to yield inactive lysoPAF. This study focused on the influence of water-immersion stress on serum PAF acetylhydrolase activity. The enzyme activity was determined by measurement of [3H]acetate produced from 1-O-alkyl-2-[3H]acetyl-sn-glycero-3-phosphocholine upon precipitation of the complex of the radioactive substrate and albumin with trichloroacetic acid. The onset of water-immersion stress caused the development of gastric lesions associated with a significant increase in serum PAF acetylhydrolase activity. Serum PAF acetylhydrolase may leak into the blood from some tissues in rats with gastric injury induced by water-immersion stress and might control the action of PAF.
1-Alkyl-2-acetylglycerophosphocholine Esterase↗
Gastric mucosal damage induced in rats by intravenous administration of platelet-activating factor.
We examined the time courses for gastric mucosal hemodynamics and lipid peroxides after intravenous infusion of PAF (platelet-activating factor). The gastric mucosal hemodynamics were continuously monitored by laser-Doppler flowmetry and reflectance spectrophotometry during 20 min infusion of PAF and the subsequent 60 min. Gastric mucosal damage was assessed by microscopical scoring and measurement of thiobarbituric acid (TBA) reactants. Intravenous infusion of PAF caused macroscopical gastric mucosal damage, hemodynamic disturbance, a reduction in blood pressure and elevation of TBA reactants. These changes did not recover to control levels, even at 60 min after PAF infusion. The mucosal injury caused by the hemodynamic disturbance (congestion) was related to the elevation of TBA reactants, that reflect lipid peroxidation and oxygen-derived free radicals.
Animals↗
Ultrasonically guided percutaneous ethanol injection therapy for hepatocellular carcinoma.
Ultrasonically guided percutaneous ethanol injection therapy (US-PEIT) was performed in 26 patients with hepatocellular carcinomas (HCC) in whom neither surgery nor transcatheter arterial embolization (TAE) was indicated, or TAE had proved ineffective. Comparison of results by various diagnostic imaging techniques with histopathological findings revealed that tumor necrosis after US-PEIT was correlated with increased echogenicity of the tumor by US, decreased density of the tumor and disappearance of contrast enhancement by computed tomography (CT), and change to a lower signal in the tumor by magnetic resonance imaging [MRI, 0.15 T permanent magnet, spin-echo sequence, repetition time (TR)/echo time (TE) = 2000/80 ms]. Thus, findings by imaging are useful in evaluating the initial effect of US-PEIT. Of three specimens obtained by liver resection and three obtained at autopsy, four showed complete necrosis after US-PEIT (maximum tumor diameter, 3 cm). This method also appeared to be effective in cases of capsular invasion. In this study, the 2-yr survival rate of patients with HCC was 75%. Although this study was not a controlled clinical trial, we conclude that US-PEIT may be a potentially effective treatment for HCC.
Administration, Cutaneous↗