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H Asakura

Publications and source records attributed to H Asakura.

At least 289 records · Page 16Linked to original sources
PubMed1993

Fucosylation index of alpha-fetoprotein, a possible aid in the early recognition of hepatocellular carcinoma in patients with cirrhosis.

We report here on three patients with cirrhosis for whom an early recognition of hepatocellular carcinoma was made possible by the measurement of the degree of fucosylation (fucosylation index) of alpha-fetoprotein. Increased levels of this index associated with a moderate increment of serum concentration of alpha-fetoprotein were observed in three patients with cirrhosis who showed no indication of hepatocellular carcinoma by several imaging modalities. Four years after the onset of an increase in the fucosylation index, small hepatocellular carcinoma with a tumor diameter less than 2 cm was revealed in case 1. In cases 2 and 3, small hepatocellular carcinomas were detected 24 mo and 9 mo, respectively, after the first sign of the increase in the index. However, the development to hepatocellular carcinoma was not detected in five patients with cirrhosis in whom continuous increments of serum concentration of alpha-fetoprotein with low levels of fucosylation index were observed during the prospective follow-up from 3 to 9 yr. These findings indicated that the fucosylation index of alpha-fetoprotein can be used as an aid in an early recognition of hepatocellular carcinoma, especially in patients with cirrhosis during the follow-up process in which the moderate increment of serum concentration of alpha-fetoprotein is noted.

Carcinoma, Hepatocellular↗
PubMed1993

Exocrinopathy resembling Sjögren's syndrome induced by a murine retrovirus.

BACKGROUND: Sjögren's syndrome (SS) is characterized by lymphocytic infiltration into, and destruction of exocrine glands, resulting in dryness of the mouth and eyes. The disease is considered to have an autoimmune etiology, however, its etiopathogenesis remains largely unknown. Recently, retrovirus is suggested to participate in the pathogenesis of SS, because SS-like lesions are reported in HIV infection or in human T cell leukemia virus type I infection. Moreover, human intracisternal A-type retroviral particles are reported to be detected in SS patients. During the course of our study on the histopathology of mice infected with a murine retrovirus, we happened to find SS-like exocrinopathy in those mice. EXPERIMENTAL DESIGN: Four-week-old C57BL/6 (B6) mice were injected intraperitoneally with LP-BM5 murine leukemia virus. This virus is known to induce splenomegaly, lymphadenopathy followed by lymphoid malignancy, and profound immunodeficiency in sensitive strains of mice. From 4 to 16 weeks after the virus inoculation, the infected mice were sacrificed and their submandibular and lacrimal glands were analyzed light and electron microscopically and immunohistochemically. The existence of the virus in the lesion in situ was also analyzed by the same method, and additionally by a polymerase chain reaction method. RESULTS: Periductal lymphocytic infiltration into the submandibular and lacrimal glands was observed in all the virus-infected mice at 4 weeks after the infection and progressed with time. Extraglandular lymphocytic infiltration was also observed in liver, kidney, lung, and pancreas. Immunohistochemical examination revealed that most infiltrating cells into the glands were composed of CD3+ T cells (CD4-dominant), Mac-1+ cells, and B220+ cells. The virus genome was detected in submandibular glands by immunohistochemistry or by polymerase chain reaction. In addition, retroviral particles were secreted into the lumen of exocrine ducts of submandibular glands. CONCLUSIONS: This might be an SS animal model that is induced by a certain defined retrovirus. This experimental system might provide us with valuable information for analyzing the mechanisms of how a retrovirus could induce SS.

Animals↗
PubMed1993

Detailed characterization of gamma delta T cells within the organs in mice: classification into three groups.

gamma delta T cells are known to localize preferentially in the epithelial regions and the hepatic sinusoids, and exhibit highly restricted V gene usage depending on their location. In the present study, gamma delta T cells in mice were further characterized in terms of their expression of the interleukin-2 receptor beta-chain (IL-2R beta), CD4 and CD8, and CD8 alpha and beta. This experiment was arranged to investigate whether gamma delta T cells have different properties depending on the organs and how gamma delta T cells are different from extrathymic alpha beta T cells, i.e. alpha beta T cells in the liver and intraepithelial lymphocytes in the intestine, in terms of the above phenotypes. Three-colour immunofluorescence tests using monoclonal antibodies revealed that gamma delta T cells can be classified into three groups: gamma delta T cells of the liver type are all IL-2R beta+, are comprised of double-negative (DN) CD8-CD4- and single-positive CD8+ (no CD4+) cells, and express CD8 alpha+ beta-; gamma delta T cells of the thymus type are a mixture of IL-2R beta+ and IL-2R beta-, are mainly DN, and express CD8 alpha+ beta+ if they carry CD8 antigens; and gamma delta T cells of the intestine type are also IL-2R beta+ or IL-2R beta-, are all CD8+, and express CD8 alpha+ beta-. gamma delta T cells in the spleen of normal mice are of the thymus type, while gamma delta T cells in the spleen of athymic nude mice seem to be of the liver type. All these properties of gamma delta T cells resemble those of extrathymic alpha beta T cells rather than regular alpha beta T cells of thymic origin. The present results reveal that gamma delta T cells and other extrathymic alpha beta T cells have many properties in common as primitive lymphocytes in phylogenetic development.

Animals↗
PubMed1992

Prothrombin Himi: a compound heterozygote for two dysfunctional prothrombin molecules (Met-337-->Thr and Arg-388-->His).

A congenitally dysfunctional form of prothrombin, Prothrombin Himi, shows reduced fibrinogen clotting activity, although it retains full hydrolytic activity toward synthetic substrates. To elucidate the structural abnormality of the variant prothrombin, we first performed genetic analysis of dysprothrombin. Polymerase chain reaction amplification of the exons 8 through 14 of the proband and her family members' prothrombin genes, which code the thrombin moiety, followed by single-strand conformation polymorphism analysis, identified two variant conformers in exon 10 specific to this family. One variant allele detected in the father was inherited by the proband and one of her sisters, and the other detected in the mother was also inherited by them. This result indicates that the proband has two different base pair changes in the gene. Sequencing showed two novel point mutations in the proband's gene. One is a T to C transition at position 8751, resulting in the substitution of threonine for methionine at codon 337 (Thrombin Himi I). The other is a G to A transition at 8904, resulting in the substitution of histidine for arginine at codon 388 (Thrombin Himi II). By sequencing analysis of her parents, it was determined that Thrombin Himi I was inherited from the father and Thrombin Himi II from the mother. These results confirm that Prothrombin Himi is compound heterozygous for two dysfunctional prothrombin molecules.

Amino Acid Sequence↗
PubMed1992

Increased levels of plasma thrombomodulin in chronic myelogenous leukemia.

Circulating blood plasma contains proteinase-degraded forms of thrombomodulin that are soluble. We quantitatively assayed the plasma levels of thrombomodulin in 15 patients with chronic myelogenous leukemia (CML) in chronic phase by method of an enzyme-linked immunosorbent assay using a monoclonal antibody to protease-degraded products of thrombomodulin. Plasma levels of thrombomodulin in patients with CML at diagnosis were significantly increased (19.5 +/- 6.2 ng/ml: means +/- SD) compared with the levels in normal controls (8.0 +/- 1.9 ng/ml, n = 20) (P less than 0.001). Fibrin degradation products (D-dimer), thrombin-antithrombin III complex, and plasmin alpha 2-antiplasmin complex were almost normal, suggesting that intravascular coagulation or plasmin-mediated fibrinolysis little occurred in these patients. On the other hand, the plasma levels of elastase-alpha 1-proteinase inhibitor (E-alpha 1PI) complex, which was the indicator of released leukocyte elastase, were significantly increased in CML (P less than 0.0001). The plasma levels of thrombomodulin and E-alpha 1PI complex were decreased in parallel with decline of leukocyte counts in 10 patients with CML following anti-leukemic therapy. Furthermore, a statistically significant correlation was observed between the plasma levels of thrombomodulin and E-alpha 1PI complex obtained at 39 time points in 15 patients with CML (r = 0.81, P less than 0.001). These results suggest that the increased plasma levels of thrombomodulin in CML may be partly caused by leukocyte elastase, which may split the surface thrombomodulin and release protease-degraded fragments of it into the circulation.

Antineoplastic Agents↗
PubMed1992

Role of endothelin in disseminated intravascular coagulation.

We examined the changes in plasma levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, in 47 cases of disseminated intravascular coagulation (DIC) to investigate the role of ET-1 in DIC and its relation to multiple organ failure (MOF). A significant elevation of plasma levels of ET-1 was observed in some cases of DIC, especially in patients with sepsis, blastic crisis of chronic myelogenous leukemia, and cancer. However, no such significant elevation was observed in patients with acute promyelocytic leukemia (APL), acute leukemias except for APL, or non-Hodgkin lymphoma. Plasma levels of ET-1 were higher in patients with DIC with MOF than in those without MOF. Although the levels of ET-1 were decreased or remained low with clinical improvement in most DIC patients, the levels were further increased or remained high in patients who showed no improvement in DIC. It is suggested that ET-1 must play an important role in further progression of MOF with the vasoconstriction and microcirculatory disorders.

Disseminated Intravascular Coagulation↗
PubMed1992

Treatment of hepatocellular carcinoma with a CDDP-epirubicin-lipiodol suspension: a pilot clinico-pharmacological study.

Lipiodol injection is a useful method for detecting liver tumors, especially hepatocellular carcinoma (HCC). We therefore prepared and tested a new emulsion of lipiodol containing epirubicin and cis-diammine-dichloroplatinum (CDDP), drugs that are very effective against HCC. This CDDP-epirubicin-lipiodol suspension (CELS) was injected into 18 HCC patients via a celiac angiographic catheter. In 11 of these patients, CELS was followed by transcatheter arterial embolization (TAE) therapy. Clinical and pharmacological investigations were performed in all 18 patients, and the following results were obtained. CELS is pharmacologically and chemically stable, and both the results of the dissolution test and the serum levels of these two drugs indicate that slow release can be obtained. After the injection of CELS, serum levels of AFP and PIVKA-II decreased immediately, and no fatal clinical side effects were encountered. Although no statistically significant difference was observed, the survival (Kaplan-Meier method) of patients injected with CELS in the presence or absence of TAE therapy can be estimated to be much longer than that of patients receiving CDDP-lipiodol suspension injection in the presence (16 patients) or absence (6 patients) of TAE therapy. A combination of CELS injection and TAE therapy might be effective and useful for the treatment of HCC.

Aged↗
PubMed1992

Changes in plasma levels of thrombomodulin during haemodialysis.

We studied the changes in plasma levels of thrombomodulin (TM) known to be present on vascular endothelial cells and released into circulating blood following damage to endothelial cells, during haemodialysis in 49 patients with end-stage chronic glomerulonephritis maintained on haemodialysis. After a single haemodialysis, plasma levels of TM were significantly elevated from 38.4 +/- 13.8 ng/ml to 46.8 +/- 14.6 ng/ml (p less than 0.05). Plasma levels of TM before haemodialysis were significantly higher in the cases of long-term haemodialysis than in those of short-term haemodialysis (p less than 0.01). From these observations, increased plasma levels of TM may be due to decreased clearance of TM by renal insufficiency, or damage to endothelial cells induced by the recurrent haemodialysis. In those patients with a greater residual blood volume in a dialyser, the changes in plasma levels of thrombin-antithrombin III complex and TM during a single haemodialysis were significantly higher. From these findings, it was suggested that endothelial cell damage is more severe in patients with greater residual blood volume.

Adult↗
PubMed1992

Tenascin expression in human chronic liver disease and in hepatocellular carcinoma.

Tenascin is an oligomeric glycoprotein of the extracellular matrix synthesized during embryonic development. It is prominently expressed in a variety of tumors. The role of tenascin in liver tissue is, however, unknown. We used immunocytochemistry to define the localization of tenascin and compare this with the localization of non-collagenous proteins, such as laminin and fibronectin, in normal human liver and pathological liver from patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. In normal liver, tenascin expression was localized along the sinusoidal and vascular wall. In fibrotic liver, tenascin was also observed in the region between the hepatic parenchyma and the fibrosing portal tracts, especially in areas of piecemeal necrosis in chronic hepatitis. Immuno-EM study of liver tissue in chronic hepatitis strongly suggested the synthesis and secretion of tenascin by fat-storing cells into the space of Disse. In hepatocellular carcinoma, tenascin was expressed in both the capsule and lobular septa, but not in the sinusoidal walls of the tumors. These results led us to postulate a close relationship between the occurrence of this protein and disease processes such as fibrosis and cancer invasion.

Carcinoma, Hepatocellular↗
PubMed1992

Appearance of hepatocytelike cells in the interlobular bile ducts of human liver in various liver disease states.

Among 1,098 liver biopsy specimens obtained from patients with various liver diseases characterized by liver injury, 58 epithelial cells whose cytoplasms stained positively by the periodic acid-Schiff stain (digested with diastase) were recognized in the interlobular bile ducts of 37 specimens from 36 patients. Light microscopic study revealed that the cytoplasms of these cells were clear or stained weakly eosinophilic on hematoxylin and eosin staining and that the cell limits were distinct. From their reaction with periodic acid-Schiff stain and from electron microscopic observation it was clear that these cells contained an abundance of glycogen and were located among the normal bile duct cells surrounded by basement membrane. On electron microscopy, these cells had microvilli of equal sizes on their luminal surfaces and many irregularly sized microvilluslike cell membrane projections on their basal surfaces. They rested on basement membrane with basal spaces. These cells varied in size from 25.0 to 452.2 microns 2 (mean = 212.2 microns 2). In contrast, the sizes of normal bile duct cells and hepatocytes ranged from 20.0 to 69.3 microns 2 (mean = 34.2 microns 2) and from 113.0 to 860.3 microns 2 (mean = 447.0 microns 2), respectively. Immunohistochemical study with antiserum to cytokeratin 19, albumin and alpha 1-antitrypsin on serially cut frozen sections showed that some of these cells expressed markers of bile duct cells and hepatocytes. Some cells expressed only the markers of hepatocytes. Computer graphic three-dimensional reconstruction clearly demonstrated that these cells were located sparsely (but sometimes in groups) among normal interlobular bile duct cells, without any connection to the surrounding parenchymal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Prothrombin fragment F1 + 2 and thrombin-antithrombin III complex are useful markers of the hypercoagulable state in atrial fibrillation.

It is well known that atrial fibrillation (AF) is one of the most important diseases that predispose patients to thrombosis. We have attempted to identify patients with AF in the hypercoagulable state by measuring molecular markers such as thrombin-antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (PTF) and determining the effect of antithrombotic therapy on these markers; 83 patients with AF were studied. Increased levels of plasma TAT and PTF were more frequently observed in patients with AF and associated mitral stenosis than in patients with AF alone. In cases of AF without mitral stenosis, plasma levels of TAT and PTF were significantly lower in those patients receiving antithrombotic agents (aspirin or warfarin) than in those receiving no antithrombotic agents. Furthermore, plasma levels of PTF were significantly lower in patients given warfarin than in those receiving aspirin. These results suggest that (1) patients with AF and mitral stenosis who are not given warfarin are in an extremely hypercoagulable state and (2) some patients with AF without mitral stenosis who are not given antithrombotic agents are also moderately hypercoagulable. In vivo activation of blood coagulation was more effectively controlled in patients receiving warfarin than in those taking aspirin.

Aged↗
PubMed1991

Prothrombin Himi; an abnormal prothrombin characterized by a defective thrombin activity.

An abnormal prothrombin has been detected in a 26-year-old female, who had no history of excessive bleeding. Prothrombin activity was approximately 10% when measured using either the classical one-stage assay or the assay with Echis carinatus venom, whereas prothrombin antigen level was normal. In keeping with current nomenclature practices, the abnormal prothrombin was designated "Prothrombin Himi". The electrophoretic behavior and calcium binding properties of Prothrombin Himi did not differ significantly from normal. Prothrombin Himi was isolated by chromatography on Q-Sepharose. Electrophoretic migration of the purified abnormal prothrombin on SDS-PAGE was normal. Upon prothrombin activation by Echis carinatus venom, the clotting activity produced from Prothrombin Himi was only 37% of the normal level after 90 minutes of the activation time, where as the amidolytic activity was almost the same as normal. The cleavage patterns of Prothrombin Himi by factor Xa or Echis carinatus venom investigated by SDS-PAGE, were found to be normal. These results indicate that Prothrombin Himi was characterized by a defective thrombin enzymatic activity.

Adult↗
PubMed1991

The usefulness of simultaneous determinations of glucosaminylation and fucosylation indices of alpha-fetoprotein in the differential diagnosis of neoplastic diseases of the liver.

The degrees of glucosaminylation (glucosaminylation index) and fucosylation (fucosylation index) of alpha-fetoprotein (AFP) were determined in serum samples of 351 patients with hepatocellular carcinoma (HCC), 47 with carcinoma metastatic to the liver from digestive organs, five with mixed cholangiocellular and HCC, and 176 with benign liver diseases. The glucosaminylation index of AFP in patients with carcinoma metastatic to the liver (42 +/- 23%, mean +/- SD) was significantly higher than that in patients with HCC (5 +/- 7%, P less than 0.001) or that in patients with benign liver diseases (2 +/- 4%, P less than 0.001). The fucosylation indices of AFP in patients with carcinoma metastatic to the liver, with HCC, and with benign liver diseases were 76 +/- 25%, 42 +/- 30%, and 4 +/- 6%, respectively. Thus, the fucosylation indices of AFP were high in two neoplastic liver diseases (carcinoma metastatic to the liver and HCC) and low in benign liver diseases, whereas the glucosaminylation indices were high in carcinoma metastatic to the liver but low in HCC and benign liver diseases. When the values of 30% and 80% were used as the level of the glucosaminylation and fucosylation indices, respectively, to discriminate carcinoma metastatic to the liver from HCC, 40 of 47 patients with carcinoma metastatic to the liver (85%) were able to be discriminated from HCC (sensitivity). The specificity, the positive predictive value, and the overall accuracy were 86% (302/351), 45% (40/40 + 47 + 3 - 2) and 86% (40 + 302/47 + 351), respectively. These data suggest that the combined information in these two indices provides a potent criterion for the diagnosis of neoplastic diseases of the liver.

Adenoma, Bile Duct↗
PubMed1991

Changes in plasma levels of tissue-plasminogen activator/inhibitor complex and active plasminogen activator inhibitor in patients with disseminated intravascular coagulation.

Plasma levels of tissue-plasminogen activator.plasminogen activator inhibitor (t-PA.PAI) complex and active PAI were assayed in 58 cases of disseminated intravascular coagulation (DIC). A significant elevation of both parameters was observed in most cases of DIC, especially in patients with non-Hodgkin lymphoma, sepsis, or some patients with acute leukemia, but no such elevation was observed in patients with acute promyelocytic leukemia (APL). The levels of both parameters were higher in cases of DIC with multiple organ failure (MOF) than in those without MOF. Since no elevation of t-PA.PAI complex was observed in most cases of APL, t-PA did not seem to play an important role in the activation of fibrinolytic system in APL. Active PAI, which reflects the inhibitory regulation in fibrinolytic system, was considered to play a role in the progression of MOF. Plasma levels of active PAI were low in the cases of APL, which had no complication of MOF.

Disseminated Intravascular Coagulation↗
PubMed1991

Plasma levels of soluble thrombomodulin increase in cases of disseminated intravascular coagulation with organ failure.

We examined the changes in plasma levels of soluble thrombomodulin in 66 cases of disseminated intravascular coagulation (DIC), to investigate the damage to vascular endothelial cells and its relationship to multiple organ failure. A significant elevation of plasma levels of soluble thrombomodulin was observed in most cases of DIC, especially in patients with sepsis. However, no such significant elevation was observed in patients with acute promyelocytic leukemia. Plasma levels of both soluble thrombomodulin and active plasminogen activator inhibitor were higher in the cases of DIC with multiple organ failure than in those without multiple organ failure. The levels of soluble thrombomodulin were decreased with the clinical improvement in most cases of DIC but were further increased or remained at high levels in patients who showed no improvement of DIC. It was suggested that an increase in soluble thrombomodulin indicates the damage to the vascular endothelial cells in cases of DIC and that the damage to vascular endothelial cells plays some role in further progression of multiple organ failure.

Disseminated Intravascular Coagulation↗