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Biomedical subjects

H Asakura

Publications and source records attributed to H Asakura.

At least 307 records · Page 17Linked to original sources
PubMed1991

Hepatic lesions in alcoholic HBV carriers.

Liver biopsies were taken from 54 alcoholic HBV carriers with liver dysfunction to assess whether HBV infection or habitual drinking was the main cause of their illness. In 28 cases, ultrastructural studies were done. Results showed that 50% of the cases predominantly displayed virus-related histological changes, whereas 13% of them mainly had alcohol-related ones. Both pathological changes were evenly distributed in four cases. The remaining 15 cases showed nonspecific or other histological changes. Electron microscopy revealed that HBV core and Dane particles were seen with Mallory bodies in the same hepatocytes. Thus, we postulate that HBV-related changes are more often encountered than alcoholic ones in alcoholic HBV carriers and that HBV replication can occur even in hepatocytes bearing Mallory bodies.

Adult↗
PubMed1991

L3T4+ T cells induce hepatic lesions resembling primary biliary cirrhosis in mice with graft-versus-host reactions due to major histocompatibility complex class II disparity.

We had shown that the appearance of hepatic lesions such as epithelioid granulomas and chronic nonsuppurative destructive cholangitis (CNSDC)-like bile duct changes characteristic of primary biliary cirrhosis (PBC) in mice undergoing MHC class II-disparate graft-versus-host reactions (GVHR). To further examine the pathogenesis of the disease, we examined in the present study which T cell subset, i.e., L3T4+ or Lyt-2+ T lymphocytes, had an ability to induce such hepatic lesions. (B6 x bm12)F1 recipients were injected with unseparated T cells, L3T4+, or Lyt2+ T cells of B6 mice and on various days postinjection liver specimens were obtained. At Day 14 postinjection, livers of mice injected with whole T cells or L3T4+ T cells showed PBC-like histological changes, but none of the lesions were induced by Lyt-2+ T cells. Immunohistochemical studies revealed that Lyt-2+ as well as L3T4+ T cells were detected around bile ducts and some of them were infiltrating among bile duct epithelial cells. Kinetic studies showed that shortly after injection of L3T4+ T cells, L3T4+ T cells appeared around bile ducts and then Mac-1+ cells emerged. Lyt-2+ T cells and surface IgM+ B cells were detected on Day 5 and increased thereafter. Hepatic granulomas consisted of both L3T4+ and Lyt-2+ T cells with a few B cells. The aberrant expression of MHC class II (Ia) antigen was detected mainly at the lateral surface of bile duct epithelial cells by Day 14 postinjection. Based on these findings, the developmental mechanism of PBC-like hepatic lesions induced in mice with GVHR was discussed.

Animals↗
PubMed1991

Participation of cytoplasmic organelles in E-rosette formation.

To elucidate the mechanism of E-rosette formation between T cells and sheep red blood cells (SRBC), the effect of various agents affecting the function of cytoplasmic structures (microtubules and microfilaments) and organelles (mitochondria and rough endoplasmic reticulum) was investigated. E-rosette formation was greatly inhibited by agents that block either the energy producing system (KCN and NaN3) or the integration of microfilaments (cytochalasin B, dihydrocytochalasin B and cytochalasin D). On the other hand, there was little or no suppression by either inhibitors of protein synthesis (cycloheximide and puromycin), agents that block the polymerization of microtubules (colchicine, podophyllotoxin and vinblastine), or chemicals disconnecting surface membrane proteins from the intracellular structural proteins (chlorpromazine, dibucaine, hydrocortisone, and propranolol). The calcium ionophore A23187, which transports Ca2+ into the cytosol, inhibited the E-rosette formation in the presence of Ca2+, but not in its absence. From these results, we concluded that new synthesis of ATP and the structural integration of microfilaments are indispensable for the E-rosette formation, which is triggered by an interaction between the ligand (T11TS) and its corresponding receptor (CD2). A certain level of intracellular Ca2+ is also involved in the E-rosette formation.

Actin Cytoskeleton↗
PubMed1991

The course of disseminated intravascular coagulation is predicted by changes in thrombin-antithrombin III complex levels--is there any difference between treatment with standard heparin or low-molecular-weight heparin?

Changes in thrombin-antithrombin III complex (TAT) over a one week period studied in 42 cases of disseminated intravascular coagulation (DIC); 19 treated with standard (or unfractionated) heparin (UFH) and 23 treated with low-molecular-weight heparin (LMWH). Closer examination of short term changes in TAT (determined 2, 6, 12, 24, 48, and 72 h after starting anticoagulant therapy) was performed in ten cases of DIC; six treated with UFH and four treated with LMWH. In twelve of the 19 cases of DIC treated with UFH and 19 of the 23 cases treated with LMWH, plasma levels of TAT decreased one day after starting anticoagulant therapy, and no exacerbation of DIC was observed for the following week. In the other cases, these levels further increased and most patients had persistently high levels of TAT for the next week. Plasma levels of TAT were significantly lower in patients treated with LMWH than in those treated with UFH, which may suggest that LMWH is more beneficial in DIC. A transient increase in plasma levels of TAT was observed 6 h after the start of anticoagulant therapy in two of the six cases treated with UFH and one of the four cases treated with LMWH. From these results we conclude that fluctuation of TAT was not influenced by the type of heparin (UFH or LMWH), and that the course of DIC for the following week can be predicted by the changes in plasma TAT levels one day after starting anticoagulant therapy.

Antithrombin III↗
PubMed1991

Transient lupus anticoagulant induced by Epstein-Barr virus infection.

A 25-year-old woman presented with an episode of left calf deep vein thrombosis and pulmonary thrombosis. She was found to have a lupus anticoagulant with anticardiolipin antibodies, some autoimmune antibodies and antibodies for primary Epstein-Barr (EB) virus infection. Six months later, lupus anticoagulant and other autoimmune antibodies were found to be negative and EB virus antibodies were shown to be seroconverted. We suggest that the transient presence of lupus anticoagulant was due to EB virus infection caused by activation of polyclonal B-lymphocytes.

Adult↗
PubMed1991

Changes in plasma adenosine during simulated birth of fetal sheep.

Adenosine is known to inhibit nonshivering thermogenesis in adult brown fat. These experiments were undertaken to test whether fetal adenosine, normally present in high concentrations, suppresses lipolysis in utero and then falls after birth, permitting thermogenesis to begin. To test this hypothesis, we measured fetal plasma adenosine concentration [ADO] using high-performance liquid chromatography in 11 fetal sheep at 135-140 days gestation during simulated birth. During an initial control period, fetal [ADO] averaged 1.9 +/- 0.3 microM, about four times maternal [ADO] (0.4 +/- 0.1 microM, P less than 0.001). The fetus was then cooled by circulating cold water through a plastic coil encircled about the fetal torso. One hour later, when fetal core temperature had decreased 2.3 degrees C, fetal [ADO] averaged 2.8 +/- 0.5 microM, a 50% increase (P less than 0.05), while thermogenesis remained inactive. Next the fetal lungs were ventilated with O2 to raise arterial Po2 to greater than or equal to 150 Torr. Fetal [ADO] decreased only slightly, and thermogenic responses were modest. Finally, the umbilical cord was occluded. Fetal [ADO] decreased rapidly and 60 min later averaged 1.1 +/- 0.2 microM, 40% below initial control (P less than 0.05) and 57% below the previous period (P less than 0.001). As [ADO] fell, strong thermogenic responses became apparent, as indicated by seven- to eightfold increases in plasma glycerol (P less than 0.001) and a doubling in fetal O2 consumption (P less than 0.001). These results are consistent with the hypothesis that high fetal [ADO] inhibits thermogenesis before birth but then decreases after cord occlusion, allowing thermogenesis to begin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1991

Point mutation, allelic loss and increased methylation of c-Ha-ras gene in human hepatocellular carcinoma.

Somatic alterations of the c-Ha-ras gene were examined in 21 Japanese patients with hepatocellular carcinoma. Restriction endonuclease analysis by double digestion with MspI and HpaII revealed that DNAs from two of 21 hepatocellular carcinoma tissues were affected by nucleotide substitution at the twelfth amino acid coding sequence of the c-Ha-ras gene. DNAs from cirrhotic noncancerous liver tissue, but not leukocytes, of one of these patients possessed the mutation, whereas DNAs from noncirrhotic liver tissue and leukocytes of the other patient did not. In one of the nine patients harboring heterozygosity for c-Ha-ras-related BamHI-fragments, the loss of one allele was demonstrated as a somatic change not only in DNA from the tumor tissue but also in DNA from the cirrhotic nontumorous tissue. In two of the 19 patients comparatively examined for digestion patterns of c-Ha-ras locus with HpaII and MspI, extensive methylation was observed as a somatic modification in both DNAs from the tumor and the cirrhotic nontumorous tissues. These results thus indicate that the genetic lesions affecting the c-Ha-ras gene do occur in human hepatocellular carcinoma and probably serve as one of the multiple steps in the process of hepatic carcinogenesis.

Adult↗
PubMed1991

Fibrinogen Kanazawa: a congenital dysfibrinogenaemia with delayed polymerization having a replacement of proline-18 by leucine in the A alpha-chain.

Congenital dysfibrinogenaemia was found in a 39-year-old female and her two children. The proposita, apparently heterozygous for this abnormality, had no episode of bleeding or thrombosis. The abnormal fibrinogen showed normal release of fibrinopeptides A and B but impaired polymerization of the fibrin monomer. Amino acid sequence analysis of the whole A alpha-chain isolated from fibrinogen Kanazawa showed a substitution of Leu for Pro at position 18 in the A alpha-chain. This substitution was corroborated by the analysis of the amino acid sequence which demonstrated the lysyl endopeptidase peptides derived from the A alpha-chain of fibrinogen Kanazawa. The minimal genetic exchange responsible for this substitution was a C----T transition in the middle position of the Pro codon. We conclude that Pro-18 in the A alpha-chain is crucial for the polymerization of the fibrin monomer.

Adult↗
PubMed1991

Thymectomy in ulcerative colitis: a report of cases over a 13 year period.

Seventy eight patients with ulcerative colitis were treated by thymectomy combined with conventional therapy. An interim analysis was made after a median follow-up of 40 months in the thymectomized group and after 25 months in 173 from a non-thymectomized group. The percentage of remission periods in the thymectomized group was significantly higher than that in the non-thymectomized group as estimated by the "patient-month" method. Histological examination of the excised thymus revealed hyperplasia of the thymic epithelial cells and/or the formation of lymphoid follicles. Anticolon antibody activity of the serum from the thymectomized patients decreased gradually and disappeared in 5 years or more. "Thymectomy via the suprasternal notch with parasternal incision" which was applied in this study, is simple and not invasive. Therefore, it is recommended that thymectomy should be considered as one of the treatment for patients who are resistant to conventional therapy.

Adolescent↗
PubMed1991

[Clinical significance of antibodies against calmodulin in patients with various liver diseases].

The sera from patients with various liver diseases were investigated for the antibody against calmodulin (CaM) extracted from bovine brain by the enzyme linked immunosorbent assay. The specificity and purity of CaM were confirmed by the Western blot technique using anti-CaM antibody (anti-CaM) positive sera. IgA class antibody was frequently detected in patients with hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH) and chronic active hepatitis (CAH). On the other hand, IgG class antibody was very often present in patients liver cirrhosis, AIH and acute viral hepatitis (AVH). Sixty seven percent of patients with AVH in the acute phase were positive for IgM class anti-CaM and 33% of patients with AVH in the convalescent phase positive respectively. In AVH, the titer of anti-CaM reached its peak on 26.3 days after the onset. The titer of anti-CaM in fulminant hepatitis was higher than that in AVH. Seventy percent of type A hepatitis patients were positive for IgM class anti-CaM, 33% of type B and 33% of type non-A non-B. These results suggest that the frequency and titer of anti-CaM may depend upon the type of hepatitis and the degree of liver cell injury.

Autoantibodies↗
PubMed1990

Depletion of CD8+ cells exacerbates organ-specific autoimmune diseases induced by CD4+ T cells in semiallogeneic hosts with MHC class II disparity.

Autoimmune diseases are known to be induced in some donor-recipient combinations of mice undergoing the graft-vs-host reaction (GVHR). In this paper, we report on the development of primary biliary cirrhosis (PBC)-like hepatic lesions and also on pancreatic insulitis in (B6 x bm12)F1 mice injected with B6 CD4+ T cells. At the sites of these lesions, cellular infiltration around ductal structure was observed. Immunohistochemical studies revealed that both CD4+ and CD8+ T cells were present in the lesions of the liver and pancreas. To clarify the role of the CD8+ T cells, which were probably of host origin, we used a mAb against the Lyt-2 molecule. Both the PBC-like hepatic lesions and pancreatic insulitis were exacerbated by eliminating CD8+ T cells from mice with MHC class II GVHR. Also, autoantibodies against the pyruvate dehydrogenase-E2 component, which has been recently found to contain an immunodominant site (autoepitope) for B cell reactivity in patients with PBC, were detected in the sera of these mice by ELISA and their presence was confirmed by immunoblotting procedures. Our findings suggest that similar mechanisms as in GVHR caused by MHC class II disparity are active in the development of PBC. It should also be noted that, in addition to the hepatic lesions, insulitis closely resembling that seen in the nonobese diabetic mouse was induced in our experimental system. The results suggest that our model provides a unique opportunity to study organ-specific autoimmune diseases. Because the effector in our experimental system was defined to be CD4+ T cells responding to Iabm12 Ag, our findings support the hypothesis that an excessive immune response directed against Ia Ag can produce autoimmune disease.

Animals↗
PubMed1990

Alkaline phosphatase of rat intestinal lymph: its characterization and the effect of fat administration.

Biological characteristics of alkaline phosphatase (ALP) from rat intestine were compared among four various fractions (brush border, cytosol, luminal and lymph) to clarify the source and route of ALP appeared in intestinal lymphatics. ALP of each fraction had the same Km values and the same heat stability and all were of intestinal type. However, lymph and cytosol ALP showed similar affinity to three kinds of lectins and were distinct from membrane and luminal ALP. On polyacrylamide gel electrophoresis (PAGE), there seems to be two types of charge isomers of intestinal ALP, namely brush border type and lymph type. On sodium dodecyl sulfate (SDS)-PAGE, the molecular weight of principal band for each form was: 130,000 for brush border type, and 160,000 for lymph type. Fat administration significantly increased the ALP activity in intestinal lumen and intestinal lymph. However, it did not change biological characteristics of ALP including binding ability to lectins and electrophoretic mobility in any of these four fractions. These results suggest that lymphatic ALP may be transported from cytosol of intestinal cells and that fat administration seems to induce quantitative change of intestinal ALP, but not to change its physiological route of transportation into intestinal lymph.

Alkaline Phosphatase↗
PubMed1990

A comparison of the molecular structure of integrated hepatitis B virus genomes in hepatocellular carcinoma cells and hepatocytes derived from the same patient.

To elucidate critical genetic elements in the development of hepatocellular carcinoma associated with hepatitis B virus DNA integration, a single integrant in hepatocellular carcinoma cells and one species of multiple integrants in hepatocytes, both obtained from the same patient, were compared structurally using molecular cloning techniques. Both hepatitis B virus integrants showed similar inverted repeat sequences consisting of two defective virus genomes. The recombination of viral DNAs seemed to be mediated by short regions of base homology near the direct repeat 1 and at other regions of the virus genomes in both integrants. The virus component in the junction with host DNAs was the cohesive end region in each identical end of the viral integrant in hepatocellular carcinoma cells and in one end of the viral integrant in hepatocytes. The structure of the integrant in hepatocellular carcinoma cells was characterized by an inverted, duplicated conformation composed not only of integrated virus genomes but also of flanking cellular sequences. It was shown to be the so-called "alpha dimer" of satellite DNA. In contrast, the flanking, nonreiterated cellular DNA in the hepatocyte-derived clone did not show discernible rearrangement. These findings suggest that a common mechanism underlies the integration of hepatitis B virus DNA so that a similar organization of inverted repeat genomes is found in hepatocellular carcinoma cells and in hepatocytes. The unstable nature of cellular DNA where DNA integration occurs may be important in generating chromosome alterations found in hepatocellular carcinoma.

Adult↗
PubMed1990

Ductal lesions of exocrine glands and insulitis induced by L3T4+ T cells following graft-versus-host reaction due to major histocompatibility complex class II disparity.

Recently, we have demonstrated characteristic hepatic lesions resembling primary biliary cirrhosis (PBC) in semiallogeneic F1 hybrid mice with major histocompatibility complex (MHC) class II-disparate graft-versus-host reaction (GVHR). In the present study, we tried to reveal other ductal lesions in extrahepatic organs, including salivary glands and pancreas. Murine strains used are C57BL/6 (B6), B6 mutant bm1, and bm12. bm1 carries a mutant gene at the H-2K locus of MHC and bm12 carries a mutant gene at the I-A locus of MHC of the B6 strain. The (B6 x bm1)F1, (B6 x bm12)F1, and (bm1 x bm12)F1 mice were injected intravenously with 1 x 10(7) B6 L3T4+ or Lyt-2+ T cells and were sacrificed on the 14th day postinjection for histological examinations. Mononuclear cell infiltration was detected around the ducts of salivary glands only in (B6 x bm12)F1 mice injected with B6 L3T4+ T cells. A moderate to marked level of cell infiltration was demonstrated in pancreas of (B6 x bm12)F1 recipients similar to nonobese diabetic (NOD) mice. By immunohistochemical examinations, infiltrating cells were shown to consist not only of L3T4+ but also of Lyt-2+ T cells, even after the inoculation of L3T4+ cells. These results are discussed in reference to mechanisms of organ-specific autoimmune diseases, especially insulitis in NOD mice which show insulin-dependent diabetes mellitus.

Animals↗
PubMed1990

A familial factor XIII subunit B deficiency.

A 32-year-old woman with a bleeding tendency born of a consanguineous marriage, was found to have factor XIII subunit B deficiency. An abnormally low level of factor XIII activity was initially noticed and this finding led to further studies of the proband and her family. The notable features were: undetectable subunit B of factor XIII in the proband and her brother and reduced levels of subunit B, 34-52%, in her parents and children. The proband's brother had a markedly decreased level of subunit A protein. The level of factor XIII subunit A in platelets of the proband was normal. The half-life of subunit A determined from the disappearance curve of infused factor XIII subunit A concentrate was approximately 3 d and this is the shortest estimate of the half-life of factor XIII to date. From these results, it is suggested that subunit A is unstable in plasma deficient in subunit B and subunit B stabilizes the A protein. This is the first report of congenital deficiency of factor XIII subunit B and this disorder is thought to be inherited as an autosomal recessive trait.

Adult↗
PubMed1990

Rate of disappearance of glycerol from plasma of fetal and newborn sheep.

The disappearance of glycerol from plasma was studied after a single intravenous injection to estimate its volume of distribution (Vdist), plasma clearance rate, and rate constant for irreversible loss (kd). Studies were repeated before and after birth of the lamb to test whether loss of the placenta could account for rapidly increasing plasma concentrations in the newborn. The disappearance of glycerol was closely described by a double-exponential model in each instance. In fetal sheep Vdist averaged 0.41 +/- 0.15 (SD) 1/kg fetal wt (n = 15). This volume decreased to 0.33 +/- 0.11 l/kg (n = 8) soon after functionally removing the placenta (by snaring the umbilical cord and maintaining the fetus with intrauterine ventilation), but the change was not significant. In newborn lambs 1-3 days of age, Vdist averaged 0.45 +/- 0.11 l/kg (n = 5, NS). Plasma clearance rate also did not change significantly, averaging 7.9 +/- 2.9, 7.9 +/- 3.8, and 9.0 +/- 5.9 ml.min-1.kg-1 in the fetus, after simulated birth, and in the newborn lamb, respectively, kd also was not altered measurably and averaged 0.020 +/- 0.006, 0.024 +/- 0.007, and 0.019 +/- 0.007 min-1 during the same time periods. Similar results were obtained by using three widely different amounts of infused glycerol. The results indicate that removal of glycerol does not depend on placental function to an appreciable extent. It is concluded that plasma glycerol concentration reflects principally glycerol turnover and, hence, lipolysis before and after birth.

Animals↗