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Biomedical subjects

H Nagashima

Publications and source records attributed to H Nagashima.

At least 235 records · Page 13Linked to original sources

Tubular structures in the hepatic nuclei of a patient with delta agent.

Liver biopsy specimens obtained from a 31-year-old female with delta-positive hepatitis were studied by routine electron microscopy. In several nuclei of hepatocytes, there were filamentous or microtubular structures 15 to 20 nm in diameter, in the vicinity of which, round particles, probably cross sections of tubular ones, were seen. In these nuclei, irregular granules approximately 20 to 30 nm in diameter were also found in clusters. However, cores of Dane particles were not found in such hepatocytes. These intranuclear microtubular structures may be associated with delta agent.

Adult↗

Decreased plasma fibronectin in liver diseases correlated to the severity of fibrotic, inflammatory and necrotic changes of liver tissue.

We applied a modified enzyme-linked immunosorbent assay (ELISA) for the measurement of human plasma fibronectin and determined the level of plasma fibronectin in 90 patients with various liver diseases and 10 normal subjects. Diagnoses were made by liver biopsy under peritoneoscopy. Plasma fibronectin was significantly decreased in liver cirrhosis patients, but not in acute hepatitis or chronic hepatitis patients. Decreased plasma fibronectin was correlated poorly with 18 laboratory tests, including liver function tests, and inflammatory marker determinations performed prior to peritoneoscopy. A correlation was found between the decreased plasma fibronectin and the severity of fibrotic, inflammatory and necrotic changes of the liver. These results suggested that the level of plasma fibronectin may reflect the severity of tissue injury resulting from chronic liver diseases.

Acute Disease↗

Injurious effects of ethanol on rat Kupffer cells.

The effects of ethanol on rat Kupffer cells were studied functionally and morphologically. Eight g ethanol per kg body weight per day was intragastrically administered to rats for 7 days. An isocaloric glucose solution was administered to control rats. The phagocytic activity of the reticuloendothelial system was measured by the carbon clearance method (57 mg carbon particles per kg body weight) on the 7th day. Kupffer cells having phagocytized carbon particles were counted under the light microscope. Kupffer cells were also observed by scanning electron microscopy. Both the carbon clearance and Kupffer cell number were lower in ethanol-administered rats (32 +/- 8 X 10(-4) mg/ml; 0.6 +/- 0.3/0.01 mm2 liver lobule) as compared to control rats (63 +/- 15; 3.1 +/- 1.0). Microvilli and filopodia of Kupffer cells were fewer in ethanol-administered rats than in control rats. Carbon clearance correlated with Kupffer cell number per 0.01 mm2 liver lobule and liver weight. These results suggest that the decrease in carbon clearance induced by ethanol is due mainly to the decrease in Kupffer cell number and partly to the decrease in Kupffer cell activity as demonstrated by the disappearance of microvilli and filopodia.

Animals↗

Increased urine level of amino-terminal peptide derivatives of type III procollagen in patients with liver diseases.

The amino-terminal peptides of type III procollagen (PIIIP) in the urine of 40 patients with various liver diseases were determined with a commercial radioimmunoassay kit. The level of urinary PIIIP (uPIIIP) was correlated well with serum PIIIP (sPIIIP) in 9 patients, the coefficient of correlation being r = 0.836 (p less than 0.01) and the regression line being y = 1.42x + 24. Urinary PIIIP consisted of at least 4 different molecular species with molecular weights of 49 k, 18 k, 10 k and 4.6 k as estimated by column chromatography on Sephadex G-100. Furthermore. uPIIIP was found to be significantly elevated in acute hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma and other liver diseases, in which the elevation of sPIIIP has been reported by others. The mean values +/- standard deviations of uPIIIP were 44.0 +/- 32.0, 60.4 +/- 32.0, 62.0 +/- 46.5, 53.0 +/- 27.1 and 48.1 +/- 22.8 ng/ml for the respective liver diseases, and 13.2 +/- 4.5 for the non-hepatic disease group.

Chromatography, Gel↗

Detection of type V collagen-degrading enzyme activity in human liver.

Type V collagen-degrading enzyme activity was detected as a metalloprotease acting at neutral pH in the human liver. Type V collagen extracted from human placenta and labeled with [1-14C] acetic anhydride was used as the substrate in the assay. Four major degradation products with relatively high molecular weights were observed upon polyacrylamide gel electrophoresis of the incubation mixture of type V collagen and liver homogenate. The significance of the measurement of this enzyme activity was discussed in relation to the clarification of the mechanism of liver fibrosis.

Collagen↗

Anti-HBs antibody of normal human subjects predominantly binds 54 K and 60 K dalton HBs polypeptides.

The structure of hepatitis B virus surface antigen (HBs) recognized by anti-HBs antibody was analyzed by western blotting using anti-HBs sera obtained from normal subjects, from rabbits immunized with purified HBs and commercially available goat serum. The HBs used had 7 components of 24 K, 27 K, 33 K, 36 K, 39 K, 43 K and 67-72 K daltons. Goat anti-HBs serum bound all of these components, while human and rabbit anti-HBs sera bound only two components (60 K and 54 K daltons), which were hardly visible in the gel even by silver staining. Mixing the 24 K and 27 K components, and the 24 K and 43 K components without reducing reagent produced several polymerized forms of HBs components including 60 K and 54 K polypeptides, which were recognized by anti-HBs rabbit serum. Other combinations of HBs components did not yield any new polymeric forms. Thus, it was concluded that the formation of anti-HBs antibody in normal subjects might predominantly require an antigenic structure of polymeric forms of specific combinations of HBs polypeptides, other than previously known antigenic determinants.

Animals↗

Studies on cellular immunity against bile proteins in primary biliary cirrhosis by the leukocyte migration inhibition test (microdroplet method).

Cellular immunity against human bile proteins was investigated by the leukocyte migration inhibition test (LMIT) with 13 primary biliary cirrhosis (PBC) patients, 10 chronic aggressive hepatitis (CAH) patients and 21 healthy adults. Hepatic bile taken from patients operated on for lithiasis of the biliary tract was fractionated into five fractions with Sepharose 6B gel. A subtoxic dose of each fraction was determined in the healthy adults, and used as the antigen for LMIT. Out of the 5 fractions, only the third fraction led to an LMIT positive response in 8 out of 11 (73%) PBC patients and in 1 out of 10 (10%) CAH patients. The difference between PBC and CAH was significant (p less than 0.005). The remaining 3 PBC patients with LMIT negative responses were all under D-penicillamine treatment. Antibody to each fraction was prepared in rabbits. Using the antibodies after absorption with human serum, the localization of the antigens which were present in each fraction was investigated immunohistochemically using human liver sections. The antigen to the anti-first fraction antibody was detected specifically in the epithelial cells of the bile ducts and the ductules, and the antigen to the anti-third fraction antibody was detected specifically on the membrane of the bile canalicules. The third fraction was fractionated into three fractions by Sephadex G-200 gel. Only the first of the 3 fractions showed an LMIT positive response in 3 PBC patients, and its molecular weight was determined to be about 500,000. It is concluded that PBC patients develop cellular immunity against canalicular-antigen-containing fractions but not ductal-antigen-containing ones.

Antigens↗

Assay procedures for cathepsin B, H and L activities in rat tissue homogenates.

Cathepsin B, H and L activities in small amounts of rat tissue homogenates corresponding to 10 micrograms protein were determined with 7-amino-4-methyl-coumarin conjugates as substrates. A new procedure for serum cathepsin H activity was also developed. High cathepsin B and H activities were found in kidney, spleen and liver. Liver cathepsin B, H and L activities in D-galactosamine-injured rats were decreased concomitantly with an increase in serum cathepsin H activity.

Animals↗

Plasma level of branched chain alpha-amino acids following its alpha-keto acid administration to rats.

To detect the effective substance accelerating the conversion of branched chain alpha-keto acids (BCKA) to corresponding amino acids, some sugars, sugar alcohols, ethanol, octanoate and ATP were tested with intravenous injection of three BCKA to rats. Plasma leucine levels 30 min after BCKA injection in rats, which were infused with 2 M solution of fructose or sorbitol, reached the significantly high peak corresponding to 860% and 790% of the basal levels. Administration of ethanol (2 or 3.5 M) or octanoate (4.5 mM) also resulted in significantly high levels of leucine in plasma following BCKA injection as compared with control. Molar ratio of plasma branched chain amino acid (BCAA)/aromatic amino acid 30 min after BCKA injection increased to 12.9 in control rats. The ratios 60 and 120 min after BCKA administration were significantly higher in rats treated with ethanol (3.5 M) or octanoate (4.5 mM) than those in control. These results suggest that infusion of the metabolites inducing high NADH/NAD ratio in their metabolic pathways results in inhibition of BCKA decarboxylation and, as a result, enhancement of transamination of BCKA into BCAA.

Adenosine Triphosphate↗

Ultrastructural observation of alpha-fetoprotein producing cells in human hepatocellular carcinoma using immunoperoxidase methods--comparison with fetal liver.

The precise sites of alpha-fetoprotein (AFP) synthesis and ultrastructural features and differences of AFP-producing cells were observed in periodate-lysine-paraformaldehyde fixed, frozen liver tissues from four human hepatocellular carcinoma (HCC) patients and three human fetuses using the direct (horseradish peroxidase-labeled Fab' fraction of anti-human AFP) immunoperoxidase method. We demonstrated that AFP was located in the membrane and cisternae of rough endoplasmic reticulum, membrane-bound ribosomes, perinuclear space and Golgi apparatus. The location and intensity of immunoreaction products of AFP in hepatoma cells varied from cell to cell and case to case, while these features tended to be regular in fetal hepatocytes. We did not observe ultrastructural differences between AFP-producing and non-producing cells adjacent to each other. These observations indicate that AFP production does not occur in morphologically distinct cell populations of hepatoma tissue and that hepatoma tissue is functionally much more heterogeneous than fetal liver.

Aged↗

Hemodynamic effects of labetalol in the dog. Comparative study in the anesthetized open-chest dog and in the conscious dog.

Hemodynamic effects of labetalol, an alpha- and beta-adrenoceptor blocking drug, were investigated in the conscious dog and in the anesthetized open-chest dog. In the conscious dog, intravenous injection of labetalol, in a dose of 0.5 mg/kg, decreased the total peripheral resistance by approximately 20% (P less than 0.01) in association with falls in blood pressure and heart rate. The total peripheral resistance of the anesthetized open-chest dog was not affected by labetalol in the presence of the same extent of blood pressure fall as results of the conscious dog. In contrast, agents which have beta-adrenoceptor blocking effect alone provided substantial elevation of the total peripheral resistance in the anesthetized dog. These results indicate that the different responses of the resistance to labetalol probably result from the vascular alpha-adrenoceptor blocking action, and also show that in the conscious state alpha-adrenoceptor blocking action of labetalol is enhanced in comparison with the effect in the anesthetized open-chest dog.

Adrenergic beta-Antagonists↗

Diagnosis, treatment and prognosis of small hepatocellular carcinoma.

Diagnosis, treatment and prognosis of hepatocellular carcinoma (HCC) of small size, not larger than 5 cm in diameter, were studied in forty-three patients with underlying cirrhosis, who were detected among one-hundred-and-sixty-five HCC cases over a period of 4.5 years from 1981 to 1985. The patients included fifteen cases with tumors smaller than 3 cm in diameter which were diagnosed HCC mostly during the follow-up period of liver cirrhosis. Among various imaging procedures, real-time linear scan ultrasonography (US) had a 91% positive HCC detection rate, hepatic angiography 93% and computed tomography (CT) 88%. Surgical treatment including partial resection, subsegmentectomy and segmentectomy, was carried out in fifteen HCC cases with well-compensated cirrhosis. Transcatheter arterial embolization (TAE) was performed in nineteen cases with severe liver dysfunction and multiple location of tumors. Three-year survival was 80% in twelve patients with hepatic resection (performed since 1981) and 19% in the TAE cases; none of the other cases survived.

Adult↗

Low incidence of post-transfusion hepatitis in patients with liver cirrhosis.

A study has been undertaken to determine the incidence of post-transfusion hepatitis in 57 patients with liver cirrhosis (non-B type) and 93 cases without liver disease, who received blood transfusion during major surgery. A significantly lower incidence of post-transfusion hepatitis (5.3%) was found in patients with liver cirrhosis than in those (17.2%) without liver disease. Two out of three cirrhotic patients with post-transfusion hepatitis progressed to the clinical state of hepatic failure.

Adolescent↗

Determination of histamine concentrations in plasma by liquid chromatography/electrochemistry.

Histamine was extracted from deproteinized plasma with Amberlite CG 50 weak cation-exchange resin (analytical recovery of [3H]histamine, 60.5%). The eluate was evaporated and histamine in the redissolved sample was condensed with o-phthalaldehyde and 2-mercaptoethanol at pH 11.5. This adduct was separated by liquid chromatography under isocratic conditions and oxidized on a glassy carbon electrode at +0.4 V for electrochemical detection. 3-Methylhistamine was used as internal standard. As little as 0.45 pmol of standard histamine condensate was detected. The histamine concentration in 88 human plasma samples appeared to be normally distributed; its mean value was 7.20 (SD 2.61) nmol/L. Authentic and extracted histamine produced similar hydrodynamic voltammograms, and exogenous and endogenous histamine gave identical chromatographic characteristics with different mobile phases or different chromatographic columns. Standard and extracted histamine had similar degradation rates when samples were incubated with diamine oxidase (EC 1.4.3.6). Analytical recovery of known amounts of histamine added to pooled plasma was 97.7% (SD 22.3%). The inter- and intra-assay CVs for histamine determinations were 9.0% and 8.6%, respectively.

Adult↗

Chronic hepatitis in the geriatric patient.

The incidence and clinical characteristics of chronic hepatitis in the elderly patient over age 61 were studied in 680 biopsied cases from 1978 to 1984. Twenty four cases of chronic hepatitis in the elderly (4% of the total cases and 8% of all chronic hepatitis patients) were detected; the incidence is much lower than liver cirrhosis. Most of these cases (96%) showed active hepatitis. They had a long-term history of liver damage and negative HBsAg and HBeAg tests. Sixty seven percent of the patients showed block formation of the liver surface and low K(ICG) values (an average of 0.12). Twenty three cases are in good performance status 3 years and 3 months following the diagnosis, but ten cases still show marked fluctuation of serum GOT and GPT activities (greater than 60 IU). K(ICG) values in 16 cases improved from 0.12 to 0.14 on average 3 years after the diagnosis, suggesting that these cases might not progress to liver cirrhosis at least in the near future.

Aged↗

Elevation of plasma glucagon-like immunoreactivity (GLI) in patients with liver cirrhosis.

Plasma glucagon-like immunoreactivity (GLI) levels were increased in patients with liver cirrhosis. The levels were not significantly correlated with plasma glucagon immunoreactivity (GI) and serum insulin levels. None of the conventional liver function tests were correlated with the GLI levels, although plasma GI levels were high in cirrhotics with hyperammonemia. A significant correlation between plasma GLI and amino acid levels was not observed in these cases. The oral glucose tolerance test (OGTT) showed a significant decrease of plasma GI levels in cirrhotics but no change of plasma GLI concentrations: cirrhotic patients with diabetes mellitus or total gastrectomy showed marked increases of GLI levels. Glucagon (Glucagon Novo) injection at a dose of 10 micrograms/kg body weight to cirrhotic patients produced marked increases of both GI and GLI levels rapidly, though the mechanism of GLI elevation could not be clearly explained.

Adult↗