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Biomedical subjects

Y Muto

Publications and source records attributed to Y Muto.

At least 343 records · Page 19Linked to original sources

Clinical significance of human hepatocyte growth factor in blood from patients with fulminant hepatic failure.

We have recently found the presence of human hepatocyte growth factor in sera of patients with fulminant hepatic failure and have purified human hepatocyte growth factor from plasma of a patient with fulminant hepatic failure. In this paper, we report the clinical significance of human hepatocyte growth factor in blood from patients with fulminant hepatic failure. The effect of sera or plasma from 17 patients with fulminant hepatic failure on liver cell growth was examined by use of adult rat hepatocytes in primary cultures. Sera or plasma from 16 of the 17 patients with fulminant hepatic failure stimulated DNA synthesis in hepatocytes more effectively than normal human serum. The mean growth-promoting activity for the 17 patients with fulminant hepatic failure was about 16 times higher than that obtained for normal human serum. This growth-promoting activity of the patients' blood was not related to sex, age, clinical outcome of the patients or type of fulminant hepatic failure, but was intimately related to the clinical grade of hepatic coma. Sera or plasma with Grade III and IV coma showed stimulatory activity on DNA synthesis more markedly than sera or plasma from patients with coma of less than Grade II. In the surviving group, this activity decreased as the hepatic coma of patients improved. In fact, this activity of sera from patients at the recovery stage showed no significant increase compared with that of normal human serum. In the group of terminal patients, this activity increased as the coma developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Production of leukotriene B4 in parenchymal and sinusoidal cells of the liver in rats treated simultaneously with D-galactosamine and endotoxin.

A study was conducted to investigate production rate of leukotriene B4 (LTB4) in parenchymal and sinusoidal liver cells of rats with acute hepatic failure (AHF). AHF was induced by simultaneous administration of D-galactosamine (GalN) and endotoxin (LPS), and parenchymal as well as sinusoidal liver cells were isolated by collagenase perfusion method. Following preincubation for 15 min, isolated cellular fractions were incubated with Ca-ionophore (2 microM) for 5 min, and levels of LTB4 in culture media before and 5 min after addition of Ca-ionophore were analyzed by HPLC. Following results were obtained: The production rate of LTB4 was found to be the highest in Kupffer cells (7.2ng/10(6) cells/5 min), followed by endothelial cells (1.1), stellate cells (0.2) and parenchymal cells (not detectable). The production rate of LTB4 in both Kupffer cells and endothelial cells was found to reach a maximum in the fraction isolated 60 min after administration of GalN and LPS. Treatment with AA861, one of the selective inhibitors of 5-lipoxygenase, was shown to reduce the production of LTB4 in Kupffer cells to 53% at 10(-7)M and above 99% at higher than 10(-5)M. In conclusion, the majority of LTB4 generated in the liver of rats with AHF was found to be synthesized in Kupffer cells and, to a lesser extent, in endothelial cells, and the enhanced production of LTB4 was found to be greatly inhibited by treatment with AA861.

Acute Disease↗

Effect of long-term oral supplementation with branched-chain amino acid granules on the prognosis of liver cirrhosis.

A study was conducted to investigate the cumulative survival rates among groups of patients with liver cirrhosis who were stratified by plasma branched-chain amino acid (BCAA)/aromatic amino acid (AAA) molar ratio (BCAA/AAA), and to evaluate the effect of long-term oral supplementation with BCAA on the prognosis of cirrhotics with noticeably lower BCAA/AAA molar ratio. When 104 patients with liver cirrhosis were divided into three groups on the basis of BCAA/AAA molar ratio, i.e., BCAA/AAA greater than or equal to 1.8 (Group 1), 1.8 greater than or equal to BCAA/AAA greater than or equal to 1.0 (Group 2), and 1.0 greater than BCAA/AAA (Group 3), Group 1 showed the highest cumulative survival rate, followed, respectively, by Groups 2 and 3 (P less than 0.05). In 20 cases of non-alcoholic liver cirrhosis having BCAA/AAA less than 1.8, oral supplementation with branched-chain amino acid granules (BCAA-G) for 6 months or more (median 27 months, range 7-62 months) brought about significant increase of plasma BCAA concentration, BCAA/AAA molar ratio, and serum albumin concentration. Furthermore, the 20 cases with BCAA-G supplementation showed significantly higher cumulative survival rate during 2-4 years as compared to the control cases matched for age, sex, and etiology (involvement of hepatitis B virus). These findings indicate that long-term oral supplementation with BCAA to cirrhotic patients provides beneficial effect on the prognosis by improving protein malnutritional status and consequently delaying fatal complications such as hepatic failure and gastrointestinal bleeding.

Adult↗

Electron microscopic study of the blood-brain barrier in rats with brain edema and encephalopathy due to acute hepatic failure.

An electron microscopy study was conducted to investigate structural as well as functional changes of the blood-brain barrier in hepatic encephalopathy. Hepatic encephalopathy was induced in rats by two-stage hepatic devascularization producing ischemic liver damage. The permeability of the blood-brain barrier to lanthanum, horseradish peroxidase and [3H]inulin was determined, with electron microscopy performed on capillaries from different regions of rat brain. Marked swelling of the perivascular astroglial foot process and dilatation of extracellular spaces were observed in the cerebral cortex, pons, basal ganglia and cerebellar cortex in rats with acute hepatic failure. Diffusion of lanthanum and reaction products of horseradish peroxidase were completely restricted by intercellular tight junctions, but there was a significant increase in the amount of [3H]inulin leaking out of the capillaries in the cerebral cortex in rats with acute hepatic failure as compared with controls. [3H]inulin was found mainly in vesicles, vacuoles and endoplasmic reticulum. Our results indicate that brain edema in acute hepatic encephalopathy is mainly of the cytotoxic type and, to a lesser extent, of the vasogenic type, due to the increase of vascular permeability via the vesicle system.

Animals↗

Determination of the integrated CT number of the whole liver in patients with severe hepatitis: as an indicator of the functional reserve of the liver.

A study was conducted to estimate the functional reserve of the liver of patients with severe hepatitis by computed tomography (CT), in particular employing the integrated CT number of the whole liver (ICTN). ICTN was calculated by integrating the product of "area" times "mean CT number" of the liver in each CT slice for the entire height of the liver. The following results were obtained: 1) In patients with fulminant hepatitis (FH) as well as those with subacute hepatitis (SAH), ICTN was found to be significantly lower as compared to that of patients with acute hepatitis (AH) or non-hepatic diseases. In addition, in FH and SAH patients, ICTN showed a larger degree of decrease when compared with such conventional parameters as either estimated liver volume or mean hepatic CT number. Thus, ICTN seems to more sensitively reflect the changes in functional reserve of the liver. 2) ICTN showed significant positive correlations with prothrombin time and plasma BCAA/AAA ratio, and a significant negative correlation with plasma methionine level. 3) Time course of changes in ICTN correlated well with the clinical features of severe hepatitis. In particular, patients with initial ICTN values above 20 l.HU/m2 of body surface area showed significantly higher survival rate than those with initial ICTN below 20. In conclusion, ICTN well indicates the functional reserve of the liver, and is further suggested to be valuable as a parameter to predict the prognosis of patients with severe hepatitis.

Acute Disease↗

Tetramer Bence Jones protein in the immunoproliferative diseases. Angioimmunoblastic lymphadenopathy, primary amyloidosis, and multiple myeloma.

The authors report the clinical features and the results of immunochemical studies of patients with angioimmunoblastic lymphadenopathy, primary amyloidosis, and multiple myeloma, each of whom had in the serum and urine multiple forms of Bence Jones protein (BJP). The BJPs were isolated and purified and were shown by electrophoretic, gel filtration, and ultracentrifugal analyses to exist as tetramers and dimers. The components in two cases were kappa type and in one lambda type. The kappa tetramers consisted of two covalent dimers and the lambda tetramer two noncovalently bound dimers present in both serum and urine.

Aged↗

Proton nuclear magnetic resonance study of the solution conformation of C3a-Arg69, a 69-residue N-terminal fragment of the third component of complement.

A proton nuclear magnetic resonance (NMR) study is reported of human C3a-Arg69, which is a 69-residue fragment obtained by the tryptic cleavage of human C3. It has been shown that the combined use of a CPase/digestion difference spectroscopy method (Endo and Arata (1985) Biochemistry 24, 1561-1568) with a variety of two-dimensional NMR techniques is effective in advancing spectral assignments for structural analyses. On the basis of the results of the NMR measurements, we have concluded that: 1) the N-terminal region of the C3a molecule plays a crucial role in stabilizing the conformation of the C-terminal segment Leu63-Arg69 and 2) the existence of the core region, which is formed by segment Tyr15-Tyr59 (Huber et al. (1980) Hoppe Seyler's Z. Physiol. Chem. 361, 1389-1399), is essential in maintaining this conformation. We also suggest that the disorder of the N-terminal region, which is invisible by the X-ray crystallographic study, is due to dimerization of this molecule in the crystal.

Amino Acid Sequence↗

Behenoyl cytosine arabinoside, aclacinomycin A, 6-mercaptopurine, and prednisolone combination therapy for acute non-lymphocytic leukaemia in adults.

38 consecutive, previously untreated adult patients with acute non-lymphocytic leukaemia (ANLL) were treated with BHAC-AMP (N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine, aclacinomycin A, 6-mercaptopurine, and prednisolone) therapy between March 1980 and February 1985. 25 patients (65.8%) achieved complete remission (CR). Median CR duration and median survival of patients who achieved CR were 14, and 24 months, respectively. The Kaplan-Meier analysis revealed a probability for remaining in CR of 18.0% at 5 years. Analysis of failure cases revealed that most of them were due to resistant disease. Major toxicities were infection, diarrhoea, liver dysfunction, nausea and vomiting but these were acceptable. The results indicate that BHAC-AMP therapy is comparable to the regimen with daunorubicin and cytosine arabinoside and a further clinical trial is necessary for previously untreated adult patients with ANNL.

Aclarubicin↗

[Gastric microflora in patients receiving H2-blocker].

The gastric microflora of 21 cases receiving histamine H2-receptor antagonists (H2-blocker) were studied. Patients not given H2-blocker were also examined for gastric microflora. The gastric pH of patients who were receiving H2-blocker ranged from 1.91 to 6.51 (mean, 4.32). The gastric pH of over 5.00 was seen in 10 cases. Aerobic bacteria were isolated from 20 cases (95%). Aerobic bacterial counts per ml of gastric aspirates correlated positively with the pH of those aspirates but was little correlation between the pH of the gastric aspirates and the number of anaerobic bacteria of the samples, which were positive in 7 cases (33%). Candida and Staphylococcus were predominant isolates with positive rates of 82% and 41%, respectively. While Fusobacterium was isolated from 33% of the samples, none of the Bacteroides fragilis group organisms were isolated. It was also observed in the control group that aerobic and anaerobic bacteria were isolated from the gastric aspirates with high pH. These results suggest that in patients receiving H2-blocker anaerobes as well as aerobes may have the possibility to become pathogen for aspirate pneumonia and so on because of the overgrowth of anaerobic bacteria in the gastric fluid.

Aged↗

Macrolide accumulation by Bacteroides fragilis ATCC 25285.

The accumulation of macrolide antibiotics in Bacteroides fragilis ATCC 25285 was increased in the order erythromycin, josamycin, and rokitamycin, depending on hydrophobicity. The half-times of efflux were also prolonged in the same order. Furthermore, MICs of the antibiotics were correlated with the extent of hydrophobicity. These findings suggest that the macrolide antibiotics are accumulated in B. fragilis by means of their hydrophobic properties, and the efficient accumulation of the drugs may explain the susceptibility of this gram-negative bacterium to macrolides.

Anaerobiosis↗

[A high risk group of hepatocellular carcinoma in man, with special reference to its clinical significance for the screening of early liver cancer. Gifu Study Group for Early Liver Cancer].

A high risk group of hepatocellular carcinoma (HCC) was statistically established using multiple regression analysis of 331 cases with liver cirrhosis (LC), in which 78 cases later developed HCC. Highly contributing factors to hepatocarcinogenesis were found to be positive HBsAg, age, drinking history, sex (male), history of blood transfusion, history of acute hepatitis (or jaundice) and elevated plasma levels of alpha-fetoprotein. A prospective study was initiated in April, 1985 employing another 122 LC patients to clinically evaluate the significance of the high risk group of HCC. 28 cases with small HCC (less than 3 cm in diameter) were newly found: 4 with chronic hepatitis and 24 with LC, among whom 22 developed from the high risk group (sensitivity 92%, specificity 44%). Three year survival rate of 28 cases thus found was 56%, and causes of death of 9 fatal patients were 4 cancer death, 4 hepatic failure and 1 gastrointestinal bleeding. In conclusion, the high risk group is valuable for the screening of early liver cancers, and treatments of hepatic failure as well as of HCC itself are important to improve the prognosis of HCC patients thus diagnosed.

Carcinoma, Hepatocellular↗

[Enzymatic determination of a molar ratio of free branched-chain amino acids to tyrosine (BTR) and its clinical significance in plasma of patients with various liver diseases].

A molar ratio of free branched-chain amino acids to tyrosine (BTR) was determined in the plasma of patients with liver diseases using a new enzymatic method. In addition, clinical significance of BTR was studied by comparing particularly with that of Fischer's ratio (a molar ratio of branched-chain amino acids to aromatic amino acids (tyrosine+phenylalanine], which was obtained by conventional HPLC (Amino acid autoanalyzer, Hitachi 835). Following results were obtained: 1) Enzymatically determined branched-chain amino acids and tyrosine showed significant correlations with respective results obtained by HPLC (r = 0.937, 0.972). 2) Significant correlation was also found between enzymatically determined BTR and Fischer's ratio obtained by HPLC. Changes of BTR in clinical courses were found to be in parallel with those of Fischer's ratio. 3) BTR as well as Fischer's ratio correlated significantly with ICG R15, KICG, prothrombin time (%) and serum albumin level. 4) BTRs in patients with decompensated liver cirrhosis or with fulminant hepatitis were significantly lower than those in patients with acute or chronic hepatitis. In conclusion, new enzymatic assay of branched-chain amino acids and tyrosine as described here is quite simple method, and is also considered to be very useful parameter of the clinical conditions of patients with liver diseases, particularly representing the severity of liver diseases and the protein nutritional status.

Amino Acids, Branched-Chain↗

[Effects of supplementation with branched-chain amino acids on protein-nutritional status in rats treated by carbon tetrachloride].

A study was conducted to investigate effects of oral supplementation with branched-chain amino acids (BCAA) on protein-nutritional status in rats with liver cirrhosis. Liver cirrhosis was induced in male strain Sprague-Dawley rats by simultaneously administrating carbon tetrachloride (500 mg/kg, twice a week, intracutaneously) and phenobarbital (0.05% in drinking water, ad libitum) for 30 weeks. Following treatment with carbon tetrachloride and phenobarbital, cirrhotic rats received oral supplementation of BCAA with varying ratio among isoleucine (Ile), leucine (Leu) and valine (Val), or with varying content of total BCAA in the diet (Final content of total nitrogen was kept consistent by addition of glutamine). Nutritional efficacies of diets as described above were evaluated employing those protein-nutritional parameters as nitrogen balance and plasma levels of total protein, albumin and free neutral amino acids. Following results were obtained: 1. Compositional ratio of Ile:Leu:Val at 1:2:1.2 or at 2:1:1 was found to be more effective on diets which contained ILe:Leu:Val at 1:1:2 or either Val, Ile or Leu alone. 2. As to content of total BCAA in the diet (0, 2.5, 5, 10%), supplementation level of 2.5% was found to be most appropriate in terms of effects on nitrogen balance and on plasma protein concentration. In conclusion, 2.5% BCAA in the diet with the ratio of Ile:Leu:Val at 1:2:1.2 or 2:1:1 seems to be recommended to improve the impaired protein-nutritional status in liver cirrhosis.

Amino Acids, Branched-Chain↗

[Photodynamic therapy--its application for the treatment of esophageal cancer].

Effect of Photodynamic therapy (PDT) for esophageal cancer was discussed in this study. PDT has been performed on 9 cases of superficial esophageal cancer. All cases were followed periodically by endoscopy for 2 years 2 months to 6 years and no case has any local recurrence. But in 2 cases invaded submucosal layer, lymph node metastasis was recognized. We think PDT is one of the very effective therapies in the treatment of intramucosal cancer.

Aged↗