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Biomedical subjects

H Nagashima

Publications and source records attributed to H Nagashima.

At least 217 records · Page 12Linked to original sources
PubMed1986

Glucagon-like polypeptide and insulin contents in the brain from acute hepatic failure dogs.

Insulin contents in the thalamus-hypothalamus were significantly increased in acute hepatic failure dogs treated with dimethylnitrosamine. Glucagon immunoreactivity (GI) contents also tended to increase in the same portion of the brain. However, insulin and GI contents in the cerebral cortex and midbrain did not rise. Glucagon-like immunoreactivity (GLI) contents were much higher than GI in all the brain regions tested, but the levels were not significantly altered in hepatic failure dogs. A simultaneous infusion of insulin and glucagon to hepatic failure dogs failed to produce an elevation of insulin, GI and GLI contents even in the thalamus-hypothalamus.

Animals↗
PubMed1986

Immunohistochemical study of HLA class 1 antigens on the hepatocytes of patients with chronic hepatitis B.

In order to evaluate the role of histocompatibility antigen (HLA) class 1 antigens in the pathogenesis of liver cell necrosis, HLA class 1 antigens on hepatocytes were studied in the liver biopsy materials from 20 patients with chronic hepatitis B by the peroxidase-labeled antibody method using a monoclonal antibody to human HLA-A, B, C (Cappel Laboratories). Both increased expression of HLA class 1 antigens on the hepatocytes and decreased distribution of intrahepatic hepatitis B core antigen (HBcAg) were observed in patients with an exacerbation of the inflammatory activity. These findings suggest that expression of HLA class 1 antigens on the hepatocytes may be increased when an exacerbation of inflammatory activity develops, and may be compatible with the concept that expression of these antigens plays and important role for the lysis of hepatitis B virus (HBV)-infected liver cells by cytotoxic T cells. Furthermore, in seven patients, expression of HLA class 1 antigens was studied in the liver before and after treatment with human lymphoblast interferon (IFN)-alpha, recombinant IFN-alpha or IFN-beta. Increased expression of HLA class 1 antigens was observed in patients with decreased intrahepatic HBcAg and DNA-P in sera after IFN treatment. These results also suggest that the increase of HLA class 1 antigens by IFN may be related to the immune mechanism for the effective elimination of HBV.

Adult↗
PubMed1986

Hepatitis B virus DNA in human hepatocellular carcinoma: is the integration of hepatitis B virus DNA really carcinogenic?

Hepatitis B virus-specific DNA sequences (HBVDNA) in the liver were examined in 19 patients with hepatocellular carcinoma (HCC), 5 patients with liver cirrhosis (LC) and without HCC, 3 patients with chronic hepatitis (CH), 2 patients with metastatic liver cancer (MLC), 1 patient with primary biliary cirrhosis (PBC) and 4 patients with normal liver (NL) by the Southern blot hybridization procedure. Integration of HBVDNA was found in all 4 HCC patients with serum HBsAg, of whom one patient had HBVDNA only in the non-tumor (cirrhotic) region. Integration of HBVDNA was also detected in 4 of 8 HCC patients without serum HBsAg but with serum HBV-related antibodies, and in 2 HBsAg-positive patients of 5 LC patients. All 3 HBsAg-positive CH patients had only extrachromosomal HBVDNA. No HBVDNA was detected in the other 21 patients. Although integration of HBVDNA was observed in HBsAg-positive HCC patients with a higher frequency, integrated HBVDNA could also be detected in non-tumor regions of HCC patients and cirrhotic livers without HCC. It was concluded from these observations that integration of HBVDNA was frequently associated with HCC but might not have a direct causal effect on hepatocarcinogenesis even in HBV carriers.

Adult↗
PubMed1986

Effects of adenine arabinoside on cellular immune responses in patients with chronic hepatitis B.

The lymphocyte subsets in the peripheral blood and in liver biopsies from 4 patients with chronic hepatitis B obtained about 2-7 weeks before and after treatment with adenine arabinoside (Ara-A) were studied by a peroxidase-labeled antibody method using monoclonal antibodies against Leu-1, Leu-2a, Leu-3a, Leu-7 and Leu-10 antigens. In the peripheral blood, the percentage of Leu-2a+ (cytotoxic/suppressor) cells was significantly reduced and the ratio of Leu-3a+ (helper/inducer) to Leu-2a+ cells was increased after the treatment with Ara-A. In the liver biopsies, the numbers of Leu-1+ (pan T) and Leu-2a+ cells were significantly decreased after the treatment with Ara-A. As a result, the Leu-3a+/Leu-2a+ ratio was significantly elevated in the liver after the therapy. The majority of lymphocytes distributed at sites of hepatocytic necrosis were positive for Leu-2a. The reduced numbers of Leu-1+ and Leu-2a+ cells after the treatment were mainly due to the decrease of these cells infiltrating to the sites of hepatocytic necrosis. The numbers of other subsets (Leu-3a+, Leu-7+ and Leu-10+) changed without any specific tendency both in the peripheral blood and in the liver biopsies after the treatment. With respect to viral replication, most of the patients showed a decrease of serum DNA polymerase activity or demonstrable intrahepatic HBsAg and HBcAg after the treatment. These data suggest that T cell-mediated cytotoxicity against HBV-infected hepatocytes is diminished after treatment with Ara-A.

DNA-Directed DNA Polymerase↗
PubMed1986

Development of a monoclonal antibody identifying an antigen which is segregated to the sinusoidal and lateral plasma membranes of rat hepatocytes.

We developed a monoclonal antibody to the plasma membrane of rat hepatocytes. Immunoelectron microscopic characterization of an antigen identified by our antibody revealed that the antigen was present diffusely on the sinusoidal and lateral plasma membranes of hepatocytes but absent from the bile canalicular membrane. Sinusoidal lining cells (Kupffer cells and endothelial cells) were devoid of the antigen. Within hepatocytes, the antigen was present in the Golgi complexes, segments of endoplasmic reticulum and small vesicle-like structures. The development of the monoclonal antibody to the segregated membrane antigen of the hepatocyte in this study provides a reliable marker of specific membrane domains for use of isolation of plasma membrane surfaces and is a useful tool for investigation of the transferring mechanisms of membrane proteins to their destinations.

Animals↗
PubMed1986

Purification and characterization of a liver cell membrane specific antigen.

Antibodies against human liver cell membranes were raised in rabbits by immunizing 105,000 g precipitate of normal human liver homogenates (insoluble fraction). After absorption with non-liver antigens such as human spleen, kidney, lung homogenates and serum, the anti-liver cell membrane specific antigen (LCM) IgG fraction was prepared. The antibody reacted with both 105,000 g supernatant of the liver homogenate (soluble fraction) and Triton X-100 extract of the insoluble fraction, and with the surface of Chang liver cells. Using affinity columns to conjugate this antibody and other antibodies against non-liver antigens, LCM was prepared from the soluble fraction composed of 70K, 59K, 49K, and 31K proteins. These proteins of LCM were included in liver specific lipoprotein (LSP). The number of LCM proteins was limited to 4, although that of LSP was 8 or more. Furthermore, circulating antibodies against "LCM" were detected in patients with chronic liver diseases type B and autoimmune hepatitis by an 125I-LCM-IgG-Protein A method. Therefore, LCM may be more useful than LSP to study the immunological responses involved in liver diseases.

Animals↗
PubMed1986

Molecular hybridization methods for determination of serum HBV-DNA.

Molecular hybridization methods for determination of hepatitis B virus DNA (HBV-DNA) in serum were studied. A simple method by which serum was treated with sodium hydroxide, followed by dot hybridization procedure on filter sheets provides a sensitive and direct result for detecting HBV-DNA. Another method in which DNAs extracted from Dane particle fraction were subjected to the molecular hybridization method on a filter membrane, provided similar results although this method is time consuming. The third method in which serum was directly spotted on filter sheets, followed by alkaline-treatment seems to be less sensitive. Three filter papers, NC filter, Zeta-Probe and Biodyne, on which molecular hybridization was performed, gave similar sensitivity.

DNA, Viral↗
PubMed1986

Valvuloplasty plus fundoplasty to prevent esophageal regurgitation in esophagogastrostomy after proximal gastrectomy.

To prevent regurgitation esophagitis in esophagogastrostomy after proximal gastrectomy, valvuloplasty plus fundoplasty was carried out in 17 patients with stomach cancer or cancer of the abdominal esophagus. For this purpose, an equilateral triangular flap of 2.5 cm per side was formed at the upper margin of the remaining stomach along the greater curvature. The flap was inverted into the stomach only to serve as a valve. After the esophagogastrostomy was properly performed, fundoplasty was carried out, lifting and suturing the uppermost edge of the stomach to the esophagus along the greater curvature. To prevent pylorospasm as a result of reduced gastric volume, pyloromyotomy was also performed. The results were excellent in those followed for more than 1 year. The technique is simple and effective and, we believe, deserves further clinical evaluation.

Esophagitis, Peptic↗
PubMed1986

Ammonia detoxification by accelerated oxidation of branched chain amino acids in brains of acute hepatic failure rats.

BCAA aminotransferase and BCKA dehydrogenase activities are increased in the mitochondrial fractions from the brains of hepatic failure rats treated with two-thirds removal of CCl4-injured liver. Cerebral leucine decarboxylation was accelerated, and it well correlated with arterial blood ammonia levels. Elevation of brain ammonia content following an intraperitoneal injection of ammonium acetate to hepatic failure rats could be prevented by intravenous infusion of BCAA. Significantly increased brain glutamic acid, glutamine, and alanine contents were noted. These results suggested that accelerated brain BCAA catabolism in acute hepatic failure rats reduce the neurotoxicity of ammonia by promoting the synthesis of glutamic acid and glutamine from BCAA.

Acute Disease↗
PubMed1986

Prevention of ammonia-induced brain edema in dogs infused with a branched-chain amino acid solution.

Infusion of an ammonium acetate solution into dogs during mannitol-induced reversible opening of the blood-brain barrier resulted in a marked rise in intracranial pressure (ICP). The preventive effect of a branched-chain amino acid (BCAA) solution on ammonia-induced brain edema was tested by measuring ICP and brain water content. The BCAA solution apparently prevented ammonia-induced brain edema, indicating that BCAA accelerated ammonia detoxification in the brain.

Acetates↗
PubMed1986

Human hepatocellular carcinoma-associated changes of glycosphingolipids detected by two monoclonal antibodies FH2 and IB9.

The changes of minor glycosphingolipids associated with human hepatocellular carcinomas were studied using monoclonal antibodies. Glycosphingolipids of twelve patients were isolated from the tumor tissues and their adjacent cirrhotic liver tissues. The immunoreactivities of glycosphingolipids with two monoclonal antibodies FH2 and IB9, that define x-structure (Gal beta 1-4[Fuc alpha 1-3]GlcNAc) and sialosyl alpha 2-6galactosyl residue, respectively, were studied by a solid phase enzyme-linked immunosorbent assay and a chromatogram immunobinding assay. X-structure was detected in the upper-phase neutral glycosphingolipids from both the cirrhotic liver tissues and the tumor tissues, but was generally expressed more strongly in the latter tissues. The thin-layer chromatography patterns of x-active glycosphingolipids were more complex in the tumor tissues. Sialosyl alpha 2-6galactosyl residue was detected in two ganglioside fractions. One ganglioside with faster migration on a thin-layer chromatogram was found in both the non-tumorous tissues and the tumor tissues. Another ganglioside with slower migration was more often detected in the tumor tissues. It was concluded that some of minor glycosphingolipids detected by monoclonal antibodies FH2 and IB9 could be the 'tumor-associated' antigens.

Antibodies, Monoclonal↗
PubMed1986

Active movement of synthetic myosin filaments observed by dark-field light microscopy.

Long bipolar filaments synthesized from rabbit skeletal myosin have been visualized directly under a dark-field light microscope. It was also possible to observe movements of single myosin filaments in the presence of F-actin, which was invisible. When the two kinds of filaments were mixed (final concentrations: 17 micrograms/ml myosin and 0.6 mg/ml actin) in a medium containing 0.13 M KCl, 3 mM MgCl2, and 1 mM ATP, myosin filaments did not aggregate for a long period of time but were distributed separately in the field of microscope. Under these conditions, myosin filaments intermittently moved along their length in a bidirectional manner with a maximum instantaneous velocity of 5 micron/s. Individual filaments alternated, at random, between motile and nonmotile periods of time, with the motile fraction of filaments at any moment being roughly 10%. The in vitro movement of myosin filaments may be caused by their active sliding relative to F-actin in the background.

Actin Cytoskeleton↗
PubMed1986

Induction of human interferon-gamma mRNA analyzed by cytoplasmic dot hybridization: effect of Con A, TPA, and A23187.

The cytoplasmic dot hybridization method was improved by eliminating non-specific false signals. The non-specific binding to a probe disappeared almost completely when the hybridized nitrocellulose sheet was treated with pronase. Using this improved method we demonstrated that reagents such as 12-O-tetradecanoylphorbol-13-acetate (TPA), concanavalin A (Con A) and a calcium ionophore (A23187) could induce the expression of IFN-gamma gene of a human T-lymphoblastoid cell line, TCL-Fuj 2M, where TPA functioned synergistically with Con A and A23187. However, when the cells were cultured with the ionophore for more than one day the amount of IFN-gamma mRNA was markedly reduced to a low level.

Calcimycin↗
PubMed1986

State of hepatitis B viral DNA in the liver of patients with hepatocellular carcinoma and chronic liver disease.

In order to clarify the relationship between the integration of hepatitis B virus (HBV) DNA and human hepatocellular carcinoma (HCC), the states of HBV DNA in liver tissues were examined by the Southern blot hybridization procedure. Integration of HBV DNA was found in 12 of 25 HCC cases and 5 of 12 cirrhotic cases. Of these 17 cases, 11 were positive for serum hepatitis B virus surface antigen (HBsAg) and the remaining six were positive for more than one of the serum HBV-related antibodies. In all three cases of chronic hepatitis and 18 controls, integration of HBV DNA could not be detected. Free viral DNA was found in 12 of 15 cases with serum HBsAg. One patient without serum HBsAg also had free viral DNA in the liver. Integration of HBV DNA could be observed in HCC cases positive for serum HBsAg at the highest frequency. However, there was one HCC case from an HBsAg carrier in whom integration of HBV DNA might not have a causal effect on malignant transformation, because integrated HBV DNA could be detected only in a non-tumor region. Since integrated HBV DNA could not be detected in 13 of 25 HCC cases, other etiologic factors than the integration of HBV DNA must also be taken into consideration for HCC.

Adult↗
PubMed1986

Fatigue of isolated rat diaphragm: role of impaired neuromuscular transmission.

We compared the contributions of impaired neuromuscular transmission (transmission fatigue) and impaired muscle contractility (contractile fatigue) to fatigue of the isolated rat diaphragm. To make this comparison, we measured the differences in active tension elicited by direct muscle stimulation and by indirect (phrenic nerve) stimulation before and after fatigue induced by indirect supramaximal stimulation at varying frequencies and durations. Transmission fatigue was observed after all experimental protocols. Although significant contractile fatigue was not demonstrated after brief periods of low-frequency stimulation (6 min, 15 Hz, 25% duty cycle), it was present after longer or higher frequency stimulation. We repeated the direct stimulation in the presence of neuromuscular blockade with 6 microM d-tubocurarine to demonstrate that a reduced response to stimulation of intramuscular branches of the phrenic nerve during direct stimulation was not responsible for the apparent contractile fatigue. Since we found significant decreases in the response to direct stimulation even after neuromuscular blockade, we could verify the presence of contractile fatigue. We conclude that both contractile and transmission fatigue can occur in the isolated rat diaphragm and that transmission fatigue is a much more important factor after brief periods of fatiguing contractions.

Animals↗
PubMed1986

Effect of proximal and distal coronary pressure change on the resistance of stenotic coronary segment.

While dynamic changes in the resistance of stenotic coronary segments were recently proposed by several investigators, the mechanisms of these changes are obscure. This study was conducted to correlate changes in coronary pressure distal to the stenosis to dynamic changes in the stenosis resistance in the canine heart. Coronary pressure distal to the stenosis was raised by either proximal aortic pressure elevation or intracoronary blood infusion distal to the stenosis. The pressure rise resulted in a significant fall in the stenosis resistance. Distal coronary pressure drop induced by phlebotomy or removal of blood from the distal coronary bed caused the reverse effects on resistance. Linear regression analysis revealed a close relationship between changes in distal coronary pressure (delta DCP) and those in resistance of the stenotic coronary segment (delta RL) represented by the following equation; delta RL (dyne X cm-5 X sec X 10(-3)) = 0.50 X [delta DCP (mmHg)]-6.0 X 10(-2), r = 0.86, p less than 0.01. The results suggest that dynamic changes in stenosis resistance appear largely to be a function of the pressure changes distal to the stenosis.

Animals↗