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Biomedical subjects

M Gotoh

Publications and source records attributed to M Gotoh.

At least 217 records · Page 12Linked to original sources

[The efficacy of transarterial immuno-embolization therapy in patients with unresectable hepatocellular carcinoma].

We devised a new therapeutic modality for multiple hepatocellular carcinoma (HCC) consisting of transarterial immuno-embolization (TIE) using OK-432 and fibrinogen, and applied the treatment to 22 patients with advanced HCC who had been insensitive to TAE, and 21 patients who had no treatment. Nineteen patients had a high AFP level of more than 200 ng/ml. The serum AFP level decreased in 15 patients after TIE, and in 7 patients the AFP level decreased to less than 30%. Furthermore, a marked reduction in tumor size was observed in 69% after TIE. We report 61% 1-year, and 3-year survival rate for cases who had been insensitive to TAE, and 86% 2-year survival rate for those who selected TIE as the first choice. A high fever of more than 38 degrees C occurred in all cases, and hypotension less than 80 mmHg was observed in 42% patients. No deterioration of liver function and no disturbance of the coagulation-fibrinolysis system due to TIE except in one patient with liver failure after TIE.

Carcinoma, Hepatocellular↗

High prevalence of anti-phospholipid antibodies and anti-thyroglobulin antibody in patients with hepatitis C virus infection treated with interferon-alpha.

OBJECTIVES AND METHODS: We investigated the prevalence rate of beta 2-glycoprotein I (beta 2-GPI)-dependent antiphospholipid antibodies (aPL)[anti-cardiolipin antibody (aCL), anti-phosphadidylserine antibody (aPS), and anti-phosphatidic acid antibody (aPA)], antinuclear antibody (ANA), anti-deoxyribonucleic acid antibody (aDNA), anti-thyroglobulin antibody (aTG), and anti-thyroid peroxidase antibody (aTPO) in 56 patients with hepatitis C virus (HCV) infection and correlated the results with inteferon-alpha (IFN) treatment. RESULTS: aCL, aPS, and aPA were positive in, respectively, 7/56 (13%), 12/56 (21%), and 13/56 (23%) patients before treatment. aPS and aPA appeared in 6/44 and 9/43 and disappeared in 6/12 and 2/13 patients, respectively, after IFN treatment; the differences were statistically significant. The changes in OD readings were higher in the group of patients who became positive for aPS and aPA than in those who became negative after treatment. The positive rates of aTG and aTPO in the patient group were statistically higher than in the healthy controls, and aTG developed in four patients and disappeared in two. No obvious changes in aTPO were observed; however, the aTPO titer was increased in four previously positive patients. None of the patients positive for any antibodies developed an abnormality associated with these antibodies during an observation period of up to 1 yr. CONCLUSIONS: The pathogenesis of production and clinical significance of aPL, ATG/aTPO in this clinical setting are unclear, but immunological disturbances, such as the effects of HCV infection and/or IFN treatment, were considered to be a possibility. Further investigation is needed to clarify whether HCV/aPL- and/or aTG/aTPO-positive patients treated with IFN might develop aPL-associated complications and/or autoimmune disease(es), in the future and to confirm whether IFN treatment justifies the outcome in this clinical setting.

Adult↗

Use of a biosensor based on surface plasmon resonance and biotinyl glycans for analysis of sugar binding specificities of lectins.

We have developed a new method for analysis of the interaction between lectins and biotin-derivatized oligosaccharides involving a biosensor based on surface plasmon resonance. Complex type asialo-bi-, tri-, and tetra-antennary oligosaccharides were quantitatively converted into their biotin derivatives by incubating them with 6-(D-biotinyl)-aminohexanoyl hydrazide. This method was also applicable to sialyl sugar chains without any removal of sialic acid residues. The reaction mixture could be directly injected onto the streptavidin pre-immobilized surface of a sensor chip without any purification because of its fairly low reagent/carbohydrate molar ratio. The amounts of sugar chains required for interaction analysis by this method were as low as 1 pmol. The binding specificities of Sambucus sieboldiana lectin, Maackia amurensis lectin, Ricinus communis agglutinin-120 (RCA120), and concanavalin A could be rapidly determined qualitatively by this method. Furthermore, kinetic analysis of the interaction between RCA120, and complex type asialo-bi-, tri-, and tetra-antennary oligosaccharides revealed that both the association rate constant and the dissociation rate constant (kdiss) decreased with increasing numbers of terminal galactosyl residues. Because the tendency observed for kdiss paralleled the elution order of these oligosaccharides on RCA120 immobilized affinity chromatography, kiss might hold the key to determination of the elution order on affinity chromatography.

Agglutinins↗

Adrenocorticotropin and growth hormone secretions after intracerebroventricular administration of neostigmine in rats: their relationships to hypothalamic monoaminergic neuronal activities.

Serum adrenocorticotropic hormone (ACTH) and growth hormone (GH) concentrations were assessed simultaneously with hypothalamic neuronal activities of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) 60 min after the third cerebroventricular administration of neostigmine (a cholinesterase inhibitor) in awake rats. Serum ACTH and GH concentrations were significantly increased and decreased, respectively. Neostigmine caused significant increases in hypothalamic NE and DA activities and a significant decrease in hypothalamic 5-HT activity. The reciprocal changes of serum ACTH and GH concentrations were similar to those of hypothalamic NE and 5-HT activities. Multiple regression analyses with stepwise procedure revealed that hypothalamic NE and 5-HT activities were respectively significant determinants of serum ACTH and GH concentrations. Apart from the direct influence of neostigmine on ACTH and GH secretions, it is suggested that the changes in hypothalamic monoaminergic activities play an important role in modulating ACTH and GH secretions following the administration of neostigmine.

Adrenocorticotropic Hormone↗

Association of plakoglobin with APC, a tumor suppressor gene product, and its regulation by tyrosine phosphorylation.

Plakoglobin is a cytoplasmic protein localized in both adherens junctions and desmosomes. Little is known about its function, but it may play a role in maintaining cell junction integrity. A partly homologous protein, beta catenin, is localized mainly in adherens junctions and plays a key role in cell adhesion by associating with cadherins, a family of Ca2+ dependent cell-to-cell adhesion molecules. Recently the product of APC, a tumor suppressor gene, was found to associate with beta catenin. In this study we demonstrated that plakoglobin also associates with APC and that tyrosine phosphorylated plakoglobin associates with cadherins but not with APC. These results suggest that plakoglobin could play a role in mediating the signals of APC by mutual interaction and that this may be regulated by tyrosine phosphorylation.

Adenocarcinoma↗

Electron spin resonance signals of non-heme iron as an indicator of ischemia-reperfusion injury of the liver.

Although many different methods have been proposed to assess the viability of preserved or reperfused liver, none of them are definitive. In this study, we investigated the usefulness of electron spin resonance (ESR) spectrometry in the rat liver ischemia model. Ischemia was induced in Wistar rats weighing 250-300 g by clamping the portal triad. At 15, 30, 60, or 90 min after the clamping, the liver was reperfused by removing the clamp. Liver specimens obtained before and after the clamping and also 30 min after reperfusion were frozen with liquid nitrogen and analyzed at 140K by ESR spectrometry. Two significant signals of g-values of 2.0 and 1.96 were observed with the fresh liver. The former was thought to be a mixture of CoQ, flavin, and succinate radicals. The intensity of this signal did not change throughout the experimental period. The latter was regarded as the signal from non-heme irons of mitochondria. The intensity of this signal decreased as the ischemic time became longer (the ratio to the signal intensity of the fresh liver was 0.69 +/- 0.19, 0.22 +/- 0.08, 0.20 +/- 0.05, and 0.18 +/- 0.09 at the end of 15, 30, 60, and 90 min of ischemia, respectively). After reperfusion, each ratio recovered to 0.95 +/- 0.12, 0.77 +/- 0.06, 0.56 +/- 0.15, and 0.37 +/- 0.20, respectively. This suggests that detectable signals with Fe(II)-Fe(III) decreased and became undetectable as the reduced form of non-heme irons under the anoxic state. Then, after reperfusion, the reduced form of non-heme irons decreased and the oxidized form increased. Incomplete recovery was thought to be due to decrease in the viability or function of liver cells. ATP and energy charge had the same tendency as the non-heme iron signal observed with ESR. There was a significant correlation between the non-heme iron signal and energy charge (y = 0.73x + 0.32, r = 0.78, P < 0.001), demonstrating that the signal intensity reflects the viability or function of liver cells. This study suggests that the signal from non-heme irons detected by ESR can be a good parameter of the metabolic state of the liver in ischemia and reperfusion. This method is simple and quick and should be applicable in clinical liver transplantation.

Adenosine Diphosphate↗

Improved synthesis and the crystal structure of methyl 4,6-dideoxy-4-(3-deoxy-L-glycero-tetronamido)-alpha-D-mannopyrano side, the methyl alpha-glycoside of the intracatenary repeating unit of the O-polysaccharide of Vibrio cholerae O:1.

The crude product of deamination of the commercially available L-homoserine was acetylated and the 2-O-acetyl-3-deoxy-L-glycero-tetronolactone (18) formed was used to N-acylate methyl perosaminide (methyl 4-amino-4,6-dideoxy-alpha-D-mannopyranoside, 12) and its 2,3-O-isopropylidene derivative. The major product isolated from the reaction was the crystalline methyl 4-(4-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-alpha-D-+ ++mannopyranoside (1, 70-75%) resulting from acetyl group migration in the initially formed 2'-O-acetyl derivative. O-Deacetylation of 1 gave the title amide 2. Compound 2, obtained crystalline for the first time, was fully characterized, and its crystal structure was determined. Deoxytetronamido derivatives diastereomeric with 1 and 2, respectively, were obtained by the acylation of 12 with 2-O-acetyl-3-deoxy-D-glycero-tetronolactone (prepared from D-homoserine), and subsequent deacetylation. Structures of several byproducts of the reaction of 12 with 18 have been deduced from their spectral characteristics. Since these byproducts were various O-acetyl derivatives of 2, the title compound could be obtained in approximately 90% yield by deacetylating (Zemplén) the crude mixture of N-acylation products, followed by chromatography.

Carbohydrate Conformation↗

Corticotropin-releasing factor stimulates Ca2+ influx in cultured rat astrocytes.

Corticotropin-releasing factor (CRF) increased intracellular Ca2+ concentration in single astrocytes. The effect in increasing intracellular Ca2+ was not observed in Ca2(+)-free solution. Furthermore, CRF at concentrations more than 10 nM stimulated 45Ca2+ uptake in cultured rat astrocytes. The action was blocked by alpha-helical CRF(9-41) in a competitive manner, but not by nifedipine and 3,4-dichlorobenzamil. On the other hand, CRF did not stimulate cAMP formation, cGMP formation and phosphoinositide hydrolysis in astrocytes. These results indicate that CRF increases Ca2+ influx via an activation of CRF receptors in a cAMP-independent mechanism in cultured astrocytes.

1-Methyl-3-isobutylxanthine↗