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Biomedical subjects

H Mizuo

Publications and source records attributed to H Mizuo.

17 recordsLinked to original sources
PubMed2000

Circular double-stranded forms of TT virus DNA in the liver.

TT virus (TTV) is an unenveloped, circular, and single-stranded DNA virus commonly infecting human beings worldwide. TTV DNAs in paired serum and liver tissues from three viremic individuals were separated by gel electrophoresis and characterized biophysically. TTV DNAs in sera migrated in sizes ranging from 2.0 to 2.5 kb. TTV DNAs in liver tissues, however, migrated at 2.0 to 2.5 kb as well as at 3.5 to 6.1 kb. Both faster- and slower-migrating forms of TTV DNAs in the liver were found to be circular and of the full genomic length of 3.8 kb. TTV DNAs migrating at 2.0 to 2.5 kb, from either serum or liver tissues, were sensitive to S1 nuclease but resistant to restriction endonucleases, and therefore, they were single-stranded. By contrast, TTV DNAs in liver tissues that migrated at 3.5 to 6.1 kb were resistant to S1 nuclease. They migrated at 3.7 to 4.0 kb after digestion with EcoRI, which suggests that they represent circular, double-stranded replicative intermediates of TTV. When TTV DNAs were subjected to strand-specific primer extension and then amplified by PCR with internal primers, those in serum were found to be minus-stranded DNAs while those in liver tissues were found to be a mixture of plus- and minus-stranded DNAs. These results suggest that TTV replicates in the liver via a circular double-stranded DNA.

Base Sequence↗
PubMed1999

[Detection of TT virus (TTV) in non-B, non-C hepatitis patients with hepatocellular carcinoma, and clinical features of these patients].

A novel human DNA virus, TTvirus (TTV), was identified from a patient with posttransfusion hepatitis of unknown etiology. It is thought to be a new hepatitis virus, but the clinical significance of this virus is uncertain. We investigated the frequency of TTV viremia by PCR in 39 non-B, non-C hepatitis (NBNC) patients with hepatocellular carcinoma (HCC), and clinical features of these patients. TTV viremia was detected in 20 (51.3%) of 39 NBNC hepatitis patients with HCC. Liver cirrhosis (LC) were found in 11 (55%) of 20 TTV-positive patients and 16 (84%) of 19 TTV-negative patients (p < 0.05). The levels of AST, LDH, LAP, gamma GTP in TTV-positive patients were significantly higher than those in TTV-negative patients (p < 0.05). (AST: 58 +/- 26 vs 42 +/- 23 IU/l, LDH: 468 +/- 127 vs 366 +/- 123 IU/l, LAP: 339 +/- 242 vs 206 +/- 80 IU/l, gamma GTP: 207 +/- 207 vs 105 +/- 107 IU/l) These results suggest clinical differences between TTV-positive and TTV-negative patients in NBNC hepatitis patients with HCC.

Aged↗
PubMed1998

Second toe plantar flap for partial finger reconstruction.

Utilizing the tissue obtained from the plantar surface (metatarsophalangeal-distal interphalangeal region) of the second toe is an ideal procedure for reconstruction of partial finger tissue defects. The major advantage of this method is that it provides satisfactory aesthetic and functional improvement at the recipient site: furthermore, good results from the aesthetic point of view and minimum morbidity at the donor site are obtained. Our procedure utilizes the free neurovascular skin flap (second toe plantar flap) and full-thickness skin graft. As for the free flap, artery and nerve are obtained from the plantar neurovascular bundle and vein from the dorsal or plantar vein. All cases reconstructed with this procedure revealed satisfactory sensory restoration and aesthetic appearance. The donor sites also revealed no contracture and visible scar. In this paper, we discuss the application of this procedure for finger tissue reconstruction.

Child, Preschool↗
PubMed1995

Graves' hyperthyroidism following transient thyrotoxicosis during interferon therapy for chronic hepatitis type C.

We report a case of Graves' hyperthyroidism induced by long-term interferon (IFN) therapy. A 52-year-old woman suffered from chronic active hepatitis type C and was treated with a total of 456 x 10(6) units of IFN-alpha for 23 weeks. During the 12th week of treatment she showed transient thyrotoxicosis. One week after the termination of IFN therapy, TSH-receptor antibodies became positive and subsequently she showed Graves' hyperthyroidism. This case showed sequential manifestation from transient thyrotoxicosis to the appearance of TSH-receptor autoantibodies, and then the occurrence of Graves' hyperthyroidism during IFN therapy. The course of this case may be useful in the understanding of the pathogenesis of autoimmune hyperthyroidism.

Autoantibodies↗
PubMed1994

Thrombolysis of canine femoral artery thrombus by a novel modified tissue-type plasminogen activator (E6010).

The thrombolytic activity of a novel modified tissue-type plasminogen activator (t-PA) (E6010) was examined in a canine model with copper coil-induced femoral artery thrombus. This model, in which thrombolytic activity can be easily and directly quantified by determining changes in thrombus weight, should be useful for comparing the activities of various thrombolytic agents. Using this model, the present study showed that the thrombolytic activity of bolus intravenous injection of E6010 was identical to that of continuous intravenous infusion of recombinant t-PA at the same dose. This thrombolytic activity can be explained by changes in blood concentrations of the administered thrombolytic agents. On the other hand, administration of the thrombolytic agents dose-dependently caused significant changes in the levels of hemostatic and fibrinolytic factors. These changes were not so marked with administration of E6010, and therefore we concluded that E6010 is unlikely to cause bleeding complications after administration.

Animals↗
PubMed1991

Thrombolytic properties of a novel modified human tissue-type plasminogen activator (E6010): a bolus injection of E6010 has equivalent potency of lysing young and aged canine coronary thrombi.

The thrombolytic properties of a novel modified human tissue plasminogen activator (E6010), in which cystein 84 in the epidermal growth factor domain is replaced by serine and that has a prolonged biological half-life, were examined. The thrombolytic efficacies of E6010 and recombinant human tissue plasminogen activator (rt-PA) on the duration of coronary artery thrombus were evaluated in a canine model (123 anesthetized dogs) with copper coil-induced left anterior descending coronary artery thrombus. Thrombi established for periods of 1, 3, or 6 h, as documented by coronary arteriography, were employed. A single bolus i.v. injection of E6010 or rt-PA and an i.v. infusion of rt-PA over 60 min were compared (n = 6). Thrombolytic efficacy was evaluated by three criteria: time to reperfusion (TR), reperfusion rate at 60 min (RR), and reocclusion rate at 60 min after reperfusion (OR). With a bolus i.v. injection of E6010 at a dose of 0.2 mg/kg or an i.v. infusion of rt-PA at a dose of 0.6 mg/kg/h, these parameters were as follows: TR, 30.0 +/- 15.3 and 27.5 +/- 4.8 min; RR, 100 and 100%; OR, 17 and 33% for 1-h aged thrombi; TR, 30.0 +/- 9.5 and 35.0 +/- 8.2 min; RR, 83 and 50%; OR, 20 and 67% for 6-h aged thrombi. These data indicate that a bolus injection of E6010 is almost equally efficacious in lysing thrombi aged both 1 and 6 h. On the other hand, in the case of rt-PA, the thrombi aged 6 h were lysed significantly less than the thrombi aged 1 h. Plasma half-lives of E6010 were t1/2 alpha, 4.8 +/- 0.95 (estimated by antigen level) and 3.0 +/- 0.78 min (estimated by activity), and t1/2 beta, 51 +/- 5.4 (antigen level) and 22 +/- 7.0 min (activity). The half-lives of rt-PA were t1/2 alpha, 3.6 +/- 0.23 (antigen level) and 2.1 +/- 0.61 min (activity), and t1/2 beta, 36 +/- 2.3 (antigen level) and 7.0 +/- 3.5 min (activity). We conclude that a bolus injection of E6010 may have a more potent and longer-lasting effect than i.v.-infused rt-PA in clot lysis therapy.

Aging↗
PubMed1989

[Preparation of monoclonal antibodies against duck hepatitis B core antigen and analysis of the monoclonal antibodies].

Mice were immunized against duck hepatitis B virus core (DHBc) particles isolated from the liver of asymptomatic carrier ducks of duck hepatitis B virus (DHBV) by ultracentrifugation. Their spleen cells were fused with mouse myeloma (NS-1) cells, and 12 clones of hybridoma cells secreting antibodies against DHBc (anti-DHBc) were isolated. According to the reactivity to core particles and core peptide obtained from DHBc particles treated with SDS-2ME, the 12 antibodies were classified into two groups. Two monoclonal antibodies reacted against both core particles and core peptide (B-type), the other ten monoclonal antibodies reacted against core particles but did not react against core peptide obtained from DHBc particles treated with SDS-2 ME. (A-type). Solid phase enzyme immuno assay (EIA) using these two types of antibodies could detect core antigenisity not only in the liver homogenate but also in the DHBV infected serum. Sucrose gradient analysis and gel filtration analysis revealed this DHBc antigenisity in the serum is not carried by core particles but carried by core peptide, equivalent to HBe antigen in the serum of Hepatitis B virus (HBV) carrier. This EIA may provide sensitive test monitoring both serum DHBe antigen levels and DHBc antigen levels in the liver during DHBV infection.

Animals↗
PubMed1986

Clonal origin of human hepatoma determined by integration of hepatitis B virus DNA.

The hepatitis B virus genome is integrated in cellular DNA of human hepatocellular carcinoma from hepatitis B surface antigen-positive patients. Using this phenomenon, we determined the clonal origin of hepatocellular carcinoma from the integration mode of hepatitis B virus DNA. The molecular size and the number of restriction fragments of integrated hepatitis B virus DNA in several parts of tumors in the same liver and in metastatic tumors were compared by Southern blot analysis. Of 14 cases of hepatoma, 13 cases were monoclonal; in one case, a different clone of hepatoma was found in one part of the tumor. In three of 13 cases of monoclonal hepatoma, metastatic tumors in lymph nodes and the lung were also examined and found to be the same clone as the liver tumors. These results indicate that hepatocellular carcinomas were usually generated from a single tumor cell even though tumor cells spread in the liver and invaded other organs for a long time. Development of different clones of tumor was apparently unusual but was observed in one case of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1984

Kinetics and mechanism of in vitro uptake of amino-beta-lactam antibiotics by rat small intestine and relation to the intact-peptide transport system.

By utilizing the everted jejunum of rats, the initial uptake rates of several antibiotics were measured over a wide range of concentrations. The uptakes followed mixed-type kinetics involving saturable and non-saturable processes in parallel. The pertinent kinetic parameters for the uptake of each antibiotic were determined. The effect of cephalexin on the uptake of cyclacillin obeyed competitive inhibition kinetics, and the inhibition constant Ki was found to be equal to the Michaelis constant Kt for the uptake of cephalexin itself. In a similar way, the uptake of cephalexin was inhibited by cyclacillin. Uptakes of both cyclacillin and cephalexin were reduced significantly by several metabolic inhibitors. From the effect of temperature on the uptakes of cyclacillin and cephalexin, activation energies of 24.8 and 23.1 kcal/mole were obtained respectively. These results indicate the involvement of an active transport mechanism for cyclacillin and cephalexin. It was found that several dipeptides markedly inhibited the uptakes of cyclacillin and cefadroxil. Furthermore, the uptake of glycylglycine, a typical dipeptide, was inhibited by cyclacillin, cefadroxil, cephalexin, and cephradine. The kinetics of mutual inhibition of the uptakes of cyclacillin and glycylglycine were consistent with competitive-type inhibition. This is the first report which establishes, from a kinetic point of view, the involvement of a common transport system in the in vitro uptakes of the dipeptides and the antibiotics.

2,4-Dinitrophenol↗
PubMed1983

Inhibition by Diazepam and γ-Aminobutyric Acid of Depolarization-Induced Release of [¹⁴C]Cysteine Sulfinate and [³H]Glutamate in Rat Hippocampal Slices.

Effects of diazepam and γ-aminobutyric acid-related compounds on the release of [¹⁴C]cysteine sulfinate and [³H]glutamate from preloaded hippocampal slices of rat brain were examined by a superfusion method. Diazepam markedly inhibited the release of cysteine sulfinate and glutamate evoked either by high K⁺ or veratridine without affecting that of other neurotransmitter candidates, e.g., γ-aminobutyric acid, acetylcholine, noradrenaline, and dopamine; IC₅₀ values for the release of cysteine sulfinate and glutamate were about 20 and 7 μM, respectively. γ-Aminobutyric acid (1 to 10 μM) and muscimol (100 μM) significantly reduced high K⁺-stimulated release of glutamate. Bicuculline, which had no effect on the release at a concentration of 50 μM by itself, antagonized the inhibitory effects of diazepam and γ-aminobutyric acid on glutamate release. Similar results were obtained with the release of cysteine sulfinate except that a high concentration (100 μM) of γ-aminobutyric acid was required for the inhibition. These results indicate the modulation by γ-aminobutyric acid innervation of the release of excitatory amino acids in rat hippocampal formation, and also suggest that some of the pharmacological effects of diazepam may be a consequence of inhibition of excitatory amino acid transmission.

Animals↗
PubMed1982

Cysteine sulfinic acid in the central nervous system: uptake and release of cysteine sulfinic acid by a rat brain preparation.

Uptake and release of cysteine sulfinic acid by synaptosomal fractions (P2) and slices of rat cerebral cortex were investigated. The P2 fraction had a Na+-dependent high-affinity uptake system for cysteine sulfinic acid (Km, 12 microM), which was restricted to the synaptosomes. High-affinity uptake of cysteine sulfinic acid was competitively inhibited by glutamate, aspartate, and cysteic acid. None of the various centrally acting drugs tested specifically inhibited this transport system. Release of [14C]cysteine sulfinic acid from preloaded cortical slices or P2 fractions was examined by a superfusion method, which avoided reuptake of released [14C]cysteine sulfinic acid. High K+ (56 mM) and veratridine (10 microM) stimulated the release of cysteine sulfinic acid from slices and the P2 fraction in a partly Ca2+-dependent manner. Diazepam at concentrations of 10 and 100 microM markedly inhibited the stimulated release, but not the spontaneous release, by cortisol slices. On the contrary, it had no effect on the stimulated release of cysteine sulfinic acid from the P2 fraction.

Animals↗
PubMedDate not supplied

Mass screening for hepatocellular carcinoma: experience in Hokkaido, Japan.

Mass screening for liver cancer based mainly on abdominal ultrasound was begun in major cities of Hokkaido, Japan, in November 1981, to enable early detection and treatment of hepatocellular carcinoma (HCC). Serum alpha-fetoprotein levels were also measured to minimize false negative studies. Examinees included those who sought liver disease screening as well as high risk individuals: hepatitis B surface antigen carriers and those with a past or current liver disease, history of blood transfusion, family history of liver cancer, and more recently those with positive anti-hepatitis C antibodies. The examination was carried out on each Saturday and Sunday as one round, and by February 1992 48 rounds had been performed. A total of 8090 individuals were investigated, and HCC was detected in 91 with a detection rate of 1.12%. This rate was 1.6% among 5684 individuals who were selected for high risk. Cumulative rates of survival among these patients were 79.0% at 1 year, 43.8% at 3 years, 19.3% at 5 years and 15.4% at 7 years. These survival rates were comparable with those for the patients with HCC diagnosed during follow-up of chronic liver disease and treated at our hospital. The cost for detecting one HCC patient in this programme was 2,660,000 yen (approximately US$25,000), which was less than those for some other types of cancer in a similar setting. Considering the high detection rate in this programme, we feel that similar programmes should be encouraged and supported.

Carcinoma, Hepatocellular↗