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Biomedical subjects

G Toda

Publications and source records attributed to G Toda.

196 records · Page 11Linked to original sources
PubMed1976

An epidemic of infantile papular acrodermatitis (Gianotti's disease) in Japan associated with hepatitis-B surface antigen subtype ayw.

An epidemic of infantile papular acrodermatitis (I.P.A.) (Gianotti's disease) occurred in Matsuyama City, in south-east Japan in 1974-75. Patients ages ranged from less than one year to eight years. Hepatitis-B surface antigen (HBsAg) was detected by an immune adherence haemagglutination method in the serum samples of 48 of the 54 patients tested. HBsAg subtypes were determined by a haemagglutination-inhibition method. ayw antigens were identified in 42 patients and adr antigens in 3; it was not possible to determine subtypes in the remaining 3 patients because antigen titres were too low. Since subtype ayw and I.P.A. are extremely rare in Japan, the association of the disease with HBsAg subtype ayw is regarded as being most significant.

Acrodermatitis↗
PubMed1975

Subfractionation of rat liver plasma membrane. Uneven distribution of plasma membrane-bound enzymes on the liver cell surface.

Plasma membranes were isolated from rat liver mainly under isotonic conditions. As marker enzymes for the plasma membrane, 5'-nucleotidase and (Na+ + K+)-ATPase were used. The yield of plasma membrane was 0.6-0.9 mg protein per g wet weight of liver. The recovery of 5'-nucleotidase and (Na+ +K+)-ATPase activity was 18 and 48% of the total activity of the whole-liver homogenate, respectively. Judged from the activity of glucose-6-phosphatase and succinate dehydrogenase in the plasma membrane, and from the electron microscopic observation of it, the contamination by microsomes and mitochondria was very low. A further homogenization of the plasma membrane yielded two fractions, the light and heavy fractions, in a discontinuous sucrose gradient centrifugation. The light fraction showed higher specific activities of 5'-nucleotidase, alkaline phosphatase, (Na+ +K+)-ATPase and Mg2+-ATPase, whereas the heavy one showed a higher specific activity of adenylate cyclase. Ligation of the bile duct for 48 h decreased the specific activities of (Na2+ +K+)-ATPase and Mg2+-ATPase in the light fraction, whereas it had no significant influence on the activities of these enzymes in the heavy fraction. The specific activity of alkaline phosphate was elevated in both fractions by the obstruction of the bile flow. Electron microscopy on sections of the plasma membrane subfractions showed that the light fraction consisted of vesicles of various sizes and that the heavy fractions contained membrane sheets and paired membrane strips connected by junctional complexes, as well as vesicles. The origin of these two fractions is discussed and it is suggested that the light fraction was derived from the bile front of the liver cell surface and the heavy one contained the blood front and the lateral surface of it.

Adenosine Triphosphatases↗
PubMed1975

Phosphorylation by inorganic phosphate of sodium plus potassium ion transport adenosine triphosphatase. Four reactive states.

Native solium and potassium adenosine triphosphatase from guinea pig kidney accepted a phosphate group from radioactive inorganic phosphate to form an acyl phosphate bond at the active site in the presence or absence of sodium ion. Magnesium ion was always required. In the presence of sodium ion and absence of adenosine triphosphate, there was no phosphorylation by inorganic phosphate. Addition of unlabeled adenosine triphosphate produced a potassium-sensitive phosphoenzyme which exchanged its phosphate-group with radioactive inorganic phosphate. The dephosphoenzyme was an intermediate in this exchange. The rate constant for dephosphorylation was about 0.05 per second. Addition of rubidium ion, a congener of potassium ion, to the potassium-sensitive phosphoenzyme produced a phosphoenzyme labeled from inorganic phosphate with a corresponding rate constant of 0.26 per s. This was a rubidium-complexed phosphoenzyme. Addition of magnesium ion to potassium-sensitive phosphoenzyme converted it into insensitive phosphoenzyme, the splitting of which was not accelerated by potassium ion or by adenosine diphosphate. Its rate constant was 0.07 per s. In the absence of sodium ion and adenosine triphosphate, inorganic phosphate was incorporated directly into a similar insensitive phosphoenzyme. In the presence of potassium ion or rubidium ion, inorganic phosphate was incorporated into a potassium-complexed or rubidium-complexed phosphoenzyme which exchanged 32-P with inorganic phosphate completely in less than 3 s. Incorporation of inorganic phosphate into a complex of the enzyme with the inhibitor, ouabain, is already described in the literature. Its rate constant was about 0.02 per s. Thus there appear to be at least four reactive states of the phosphoenzyme which equilibrate measurably with inorganic phosphate, namely, potassium-sensitive phosphoenzyme, potassium-complexed phosphoenzyme, insensitive phosphoenzyme, and ouabain phosphoenzyme. Two of these reactive states are functional intermediates in native sodium and potassium ion transport adenosine triphosphatase. The results are compatible with control of the reactivity of the active site by conformational changes in the surrounding active center and with regulation of the energy level of the phosphate group according to the kind of monovalent cation bound to the enzyme.

Adenosine Triphosphatases↗
PubMed1975

Synthesis of adenosine triphosphate by way of potassium-sensitive phosphoenzyme of sodium, potassium adenosine triphosphatase.

The sodium and potassium ion pump is an intrinsic enzyme of plasma membranes. In these experiments it was driven backward in a transient two-step operation involving, first, phosphorylation of the enzyme from inorganic phosphate, and second, transfer of the phosphate group from the enzyme to ADP upon addition of a high concentration of Na+. There was no evidence of a significant concentration gradient across the membranes. Na+ presumably reached the solutions on both faces of the membrane simultaneously and provided the energy for synthesis simply as a consequence of ligand binding. An interaction free energy between the free energy of the binding of Na+ and the free energy of hydrolysis of the phosphate group on the enzyme was estimated. The experiments also suggested a feature of the transport mechanism. This is control by phosphorylation of access pathways from the solutions in contact with the faces of the membrane to an active center for cation binding. In the dephosphoenzyme access would be to the intracellular solution and in the phosphoenzyme access would be to the extracellular solution.

Adenosine Diphosphate↗
PubMedDate not supplied

Anticalmodulin autoantibody in liver diseases: a new antibody against a cytoskeleton-related protein.

An ELISA has been developed for detection of auto-antibodies against calmodulin. There was a significantly increased frequency (63.1%) of autoantibodies against calmodulin in 103 patients with chronic liver diseases as compared to that (30%) of patients with systemic lupus erythematosus and to that (6.9%) of normal subjects (p less than 0.01). IgG autoantibodies against calmodulin were detected in the patients with acute hepatitis (37.9%), chronic liver disease (45.6%) and also in the patients with systemic lupus erythematosus (30%). IgM autoantibodies against calmodulin were frequently found in patients with liver cirrhosis (52.2%), primary biliary cirrhosis (50%) and autoimmune chronic active hepatitis (38.7%), but rarely in patients with acute hepatitis (13.8%), chronic persistent hepatitis (9.5%) and systemic lupus erythematosus (0%). IgA autoantibodies against calmodulin were frequently found in liver cirrhosis (33.3%), primary biliary cirrhosis (42.9%) and autoimmune chronic active hepatitis (53.6%), but rarely in chronic persistent hepatitis (15.8%), chronic active hepatitis (14.3%) and systemic lupus erythematosus (0%). The occurrences of autoantibodies against calmodulin correlated neither with those of antismooth muscle antibody, antinuclear antibody and antimitochondrial antibody, nor with serum IgG concentrations. Autoantibodies against calmodulin did not cross-react with troponin, myosin light chain, calf thymus DNA and actin. The titer of autoantibodies against calmodulin was decreased by absorption of serum with calmodulin and the liver plasma membrane fraction. The immunoblotting experiment revealed the binding of autoantibodies against calmodulin to calmodulin. IgG fraction from a patient with autoimmune chronic active hepatitis inhibited the activation of phosphodiesterase by calmodulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMedDate not supplied

The acquired vitamin K-dependent gamma-carboxylation deficiency in hepatocellular carcinoma involves not only prothrombin, but also protein C.

Protein C, one of the vitamin K-dependent plasma proteins synthesized in the liver, was measured immunologically in normal subjects (n = 20), patients with hepatocellular carcinoma (n = 60), liver cirrhosis (n = 60), acute hepatitis (n = 16), chronic hepatitis (n = 19), malignant neoplasms other than hepatocellular carcinoma (n = 35) and patients on warfarin treatment (n = 20). We also assayed gamma-carboxyglutamic acid-complete (carboxylated) protein C in these population by using a monoclonal antibody directed against human protein C, JTC-1, which recognizes the gamma-carboxyglutamic acid domain-related conformational change induced by metal ions. We demonstrated that the plasma of patients with hepatocellular carcinoma contains considerable amounts of gamma-carboxyglutamic acid-incomplete protein C, evidenced by the significantly reduced protein C:gamma-carboxyglutamic acid/protein C:antigen ratios in hepatocellular carcinoma as compared to those seen in normal controls, other liver diseases and other malignant neoplasms (p less than 0.01). In two patients with hepatocellular carcinoma with the reduced protein C:gamma-carboxyglutamic acid/protein C:antigen ratios, successful treatment (transcatheter hepatic arterial embolization or lipiodolization of antitumor agent) led to the very rapid normalization of the ratios. Intravenous administration of vitamin K, however, induced no such effects in three other patients with hepatocellular carcinoma with the abnormality. We conclude that the impaired vitamin K-dependent gamma-carboxylation observed in patients with hepatocellular carcinoma involves not only prothrombin, but also protein C, and that the impairment is not due to vitamin K deficiency.

1-Carboxyglutamic Acid↗
PubMedDate not supplied

Detection of anti-interferon-alpha 2a antibodies in chronic liver disease.

The occurrence of antibodies to interferon-alpha 2a (anti-IFN-alpha 2a) to recombinant human IFN-alpha 2a was examined in chronic liver disease by a sensitive enzyme-linked immunosorbent assay (ELISA). Naturally occurring IgG and/or IgM anti-IFN-alpha 2a were found in one of 12 cases of chronic persistent hepatitis, four of 18 cases of chronic active hepatitis (CAH), two of 12 cases of liver cirrhosis, six of seven cases of primary biliary cirrhosis, nine of 11 cases of auto-immune CAH and none of 21 normal control subjects. Fifteen patients with viral CAH were treated with recombinant IFN-alpha 2a. Two of them were positive prior to receipt of IFN-alpha 2a and their titres increased after the therapy. Two patients became positive for anti-IFN-alpha 2a after the therapy. Absorption experiments revealed that anti-IFN-alpha 2a cross-reacted with native human leucocyte IFN-alpha and recombinant IFN-alpha 2b but not with recombinant IFN-beta and -gamma. The immunoblotting experiment confirmed the binding of antibodies to IFN. The results of anti-IFN-alpha 2a obtained by antiviral, cytopathic effect assay were in good agreement with those of IgG anti-IFN-alpha 2a, but not with those of IgM antibodies obtained by the ELISA. The ELISA described in the present study is a simple, sensitive and quantitative assay for anti-IFN-alpha 2a. It should be useful in assessing sub-specificities of anti-IFN and provide valuable information to predict the effect of IFN therapy and to elucidate the immunological abnormality in liver disease.

Antibodies↗
PubMedDate not supplied

Selectivity of serum immunoreactive prolyl 4-hydroxylase as a marker for hepatic necrosis.

To investigate the selectivity of serum immunoreactive prolyl 4-hydroxylase (S-IRPH) as a marker for hepatic necrosis, sera were taken from patients with hepatic inflammation and hepatic necrosis. The concentration of immunoreactive prolyl 4-hydroxylase in the sera was determined by radio-immunoassay, and S-IRPH and alanine aminotransferase (ALT) data were plotted. Patients with hepatic necrosis showed mainly prolyl 4-hydroxylase elevation while patients with inflammation had both prolyl 4-hydroxylase and alanine aminotransferase elevations. The addition of serum immunoreactive prolyl 4-hydroxylase to current serum markers would be useful in investigating the pathophysiology of hepatocellular damage, particularly in differentiating between hepatic necrosis and inflammation.

Adult↗
PubMedDate not supplied

Marked hypophosphatemia with decreased serum 1,25-dihydroxyvitamin D in a patient with hepatocellular carcinoma complicating liver cirrhosis.

A 61-year-old male with hepatocellular carcinoma (HCC) complicating liver cirrhosis presented hypophosphatemia progressing with HCC expansion and serum alpha-fetoprotein elevation. These changes were associated with an increased fractional excretion of phosphate and decreased theoretical phosphate threshold. There was increased nephrogenous cyclic adenosine monophosphate despite normal serum parathyroid hormone. Serum 1,25-dihydroxyvitamin D levels were markedly reduced with normal 25-hydroxyvitamin D levels. There were no symptoms of osteomalacia, however, a slightly increased osteoid seam was elicited on autopsy. The hypophosphatemia could be explained by presumed secretion from HCC of humoral factors which have a phosphaturic effect and also inhibit 25-hydroxyvitamin D-1 alpha-hydroxylase in renal tubular cells.

Biomarkers, Tumor↗