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Biomedical subjects

M Omata

Publications and source records attributed to M Omata.

At least 505 records · Page 28Linked to original sources
PubMed1986

Pathological spectrum of liver diseases in sickle cell disease.

Most pathologic studies of liver disease in sickle cell anemia and its variants were performed retrospectively on autopsy specimens, and, because of the prominent histologic features of intrasinusoidal sickling and Kupffer cell erythrophagocytosis, hepatic dysfunction was attributed to the intrahepatic sickling of erythrocytes in this hemoglobinopathy. We compared the liver histology from 19 patients who had liver biopsies to the autopsy specimens from 32 patients who succumbed to the complications of the hemoglobinopathy. In the former, nine patients had histological evidence of viral hepatitis. Four of these patients had both serological and immunohistochemical evidence of hepatitis B surface antigen. The features of biliary tree obstruction were found in two cases and alcoholic cirrhosis and sarcoid granuloma in one case each. Only one patient, who had recovered from septic shock, showed ischemic necrosis. In five patients incidentally biopsied during cholecystectomy, no significant lesions were found. Fourteen of the autopsy specimens showed ischemic necrosis, a result which was significantly different from the biopsy group. Ten cases had no significant morphologic changes other than heavy iron deposits. There were two cases with chronic active hepatitis, two with diffuse fibrosis, and one case each of cirrhosis, acute viral hepatitis, cholestasis, and giant cell hepatitis. Intrahepatic sickling and erythrophagocytosis were seen in almost all specimens and did not correlate with liver disease or transaminase elevation. Other than the patient with septic shock, ischemic necrosis was found only in postmortem material. These histological features may represent red cell destruction rather than the etiology of liver disease in these patients.

Adolescent↗
PubMed1986

Resolution of diffuse granulomatous fibrosis of the liver with antituberculous chemotherapy.

A 71-yr-old man with pulmonary tuberculosis developed jaundice, and an ultrasound examination suggested hepatolithiasis. The liver was markedly enlarged and of stony consistency. Two 2.5-cm biopsy specimens of the liver each disclosed diffuse fibrosis with giant cells; practically no normal parenchyma was seen. Ultrasonography and computed tomography disclosed multiple intrahepatic calcifications, and percutaneous cholangiography revealed stenosis of the right hepatic duct. One year after treatment with antituberculous drugs, liver biopsy specimens taken from the same areas of the liver showed nearly normal histology.

Aged↗
PubMed1986

Foscarnet decreases serum and liver duck hepatitis B virus DNA in chronically infected ducks.

Foscarnet (trisodium phosphonoformate) is a new antiviral compound with in vitro inhibitory effects against the DNA polymerases of hepadna viruses. To study the effects of the drug in chronic hepadna virus infection, we treated ducks chronically infected with duck hepatitis B virus for 10 days with either low-dose foscarnet (50 mg/kg i.p. b.i.d.), high-dose foscarnet (250 mg/kg i.p. b.i.d.), or sterile water injections. Serum duck hepatitis B virus DNA and intrahepatic replicative forms of the virus were measured using molecular biological techniques with both a double-stranded radiolabeled DNA probe and a plus-strand (noncoding) specific RNA probe. We found a dose-related decrease in serum and intrahepatic duck hepatitis B virus DNA during treatment, with a rapid return toward baseline values after the cessation of treatment. There was a disproportionate decrease in the plus strand of viral DNA with treatment. We conclude that foscarnet exerts its effect in hepadna virus infection through inhibition of viral DNA polymerase. Further study is necessary to determine whether foscarnet, by itself or in combination with other treatment modalities, has a role to play in the treatment of chronic hepatitis B infections in humans.

Animals↗
PubMed1986

In vivo study of the mechanism of action of antiviral agents against hepadna virus replication in the liver. Resistance of supercoiled viral DNA.

The mode of action of antiviral agents (interferon and adenine arabinoside) was studied in human and in animals chronically infected with hepadna virus. Interferon (36-100 megaunits) was given to 20 carrier patients, and hepatitis B virus (HBV)-DNA replicative forms were studied in pre- and post-treatment biopsies. ARA-A was given intravenously to duck hepatitis B virus (DHBV)-infected ducks. Changes in intrahepatic viral replicative forms were studied by Southern blotting using 32P-labelled HBV or DHBV probe. Our study indicates that both interferon and ARA-A seem to effectively decrease 'mature' forms of viral DNA by an effect on either mRNA or DNA polymerase. However, the supercoiled viral DNA tends to resist the treatment, and may become the transcribing template for a new cycle of viral replication after cessation of the drugs.

Animals↗
PubMed1986

Combination of prednisolone withdrawal and antiviral agents (adenine arabinoside, interferon) in chronic hepatitis B. A long-term follow-up study.

In 1981, we initiated combination therapy of short-term prednisolone withdrawal and adenine arabinoside (ARA-A) or interferon (IF) for the treatment of chronic hepatitis B. Long-term follow up (range 12-48 months) of 79 HBeAg-positive patients showed that at 24 months serum HBeAg was still positive in 77% of controls, 73% of patients receiving ARA-A or IF alone, 38% of patients receiving prednisolone withdrawal alone, and 25% of those receiving the combination therapy. The long-term follow up study revealed that the combination of an immunomodulating therapy and antiviral agents appears more effective in reducing hepatitis B virus replication than single agent treatment.

Antiviral Agents↗
PubMed1986

Ultrastructural study of a clear cell chondrosarcoma.

A lesion in the left humeral head of a 15-year-old Japanese boy was light-microscopically diagnosed as clear cell chondrosarcoma. Fresh tissues from the lesion were studied ultrastructurally. In most tumor cells, that is, clear cells, paucity of organelles, sparse free ribosomes, and low protein content in cytosol were most striking. Tumor cells had many microvilli characteristic of cartilage cells. Among scanty organelles, vesicles or cisternae of dilated rough endoplasmic reticulum were rather conspicuous, and well-developed Golgi complexes were sparse. Intercellular matrix was scanty. These results suggest that intercellular matrix substance may be synthesized substantially by rough endoplasmic reticulum, whereas the synthesized substance perhaps cannot be transported smoothly into extracellular spaces because of scanty well-developed Golgi complexes.

Adolescent↗
PubMed1986

Effects of adenine arabinoside and corticosteroid on replication of duck hepatitis B virus DNA in the liver.

Adenine arabinoside (Ara-A) therapy and abrupt withdrawal of corticosteroids have both been used in the treatment of chronic infections due to hepatitis B virus (HBV). In order to better understand the effects and mechanism of action of these treatments, we treated ducks chronically infected with duck hepatitis B virus (DHBV) with different dosage regimens of the two therapies. We measured endogenous DNA polymerase activity and used sensitive molecular biological techniques to monitor serum and intrahepatic viral replicative forms during and after drug treatment. Ara-A had a transient, dose related inhibitory effect on DHBV replication. Viral plus strand synthesis was disproportionately affected. Following the cessation of Ara-A treatment markers of viral replication returned to their baseline values. We conclude that Ara-A exerts its effect through inhibition of viral DNA polymerase. Corticosteroid treatment results in an increase in DHBV replication, but steroid withdrawal results in a short-lived transient decrease in markers of viral replication to below pretreatment values. Our results suggest that steroid withdrawal decreases hepadna virus replication through a mechanisms of immune modulation. On the basis of these results and previous trials in HBV infected patients, we predict that neither agent will efficiently eliminate viral replication in chronic hepadna virus infection when used as the sole therapeutic modality. We suggest that the differences in the mechanisms of action of Ara-A treatment and corticosteroid withdrawal be exploited, and the use of combination therapy be explored.

Adrenal Cortex Hormones↗
PubMed1985

Discordance of hepatitis B e antigen/antibody and hepatitis B virus deoxyribonucleic acid in serum. Analysis of 1063 specimens.

Hepatitis B virus DNA was determined in 1063 serum samples from 252 patients with hepatitis B surface antigen by the spot hybridization technique. The results were correlated with hepatitis B e antigen and antibody. Hepatitis B virus DNA was detected in 87% of hepatitis B e antigen-positive patients, in 18% of hepatitis B e antibody-positive patients, and in 18% of those negative for both. Discordance of antigen/antibody and hepatitis B virus DNA, i.e., the presence of the DNA in antibody-positive sera or the absence of the DNA in antigen-positive sera, was observed in 209 of 997 (21%) samples. Of 121 patients with histologic diagnosis, this discordance was observed in none of 20 patients with nonspecific changes, in 13% of 39 with chronic persistent hepatitis, in 21% of 38 with chronic active hepatitis, and in 38% of 24 with cirrhosis. Thus, hepatitis B e antigen/antibody testing alone failed to predict the presence or absence of circulating hepatitis B virion in a significant proportion of patients with advanced chronic liver disease.

Adult↗
PubMed1985

Combination of short-term prednisolone and adenine arabinoside in the treatment of chronic hepatitis B. A controlled study.

The efficacy of adenine arabinoside (Ara-A) alone or in combination with prednisolone utilizing its withdrawal effect was studied in 43 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis. Ten patients were treated with 10 mg/kg body wt of Ara-A alone for 4-8 wk. In 9 cases, prednisolone (40 mg/day) was given at a constant dosage for 4 wk before Ara-A treatment. Fourteen patients received oral prednisolone alone for 4 wk, and 10 patients served as untreated controls. Six of 9 patients (67%) undergoing the combination therapy became seronegative for hepatitis B e antigen, whereas only 4 of 24 patients (17%) treated either with Ara-A alone or prednisolone alone lost the antigen. Two of the 10 untreated patients became seronegative for hepatitis B e antigen during the same follow-up period of 9 mo. This prospective controlled study suggests that the combination of immunomodulation by steroid withdrawal and subsequent Ara-A is more effective in the treatment of patients with chronic liver disease and active hepatitis B virus replication than treatment with Ara-A alone.

Adult↗
PubMed1985

Active and inactive replication of hepatitis B virus deoxyribonucleic acid in chronic liver disease.

Little is known about the replicative forms of hepatitis B virus (HBV) in the liver in chronic liver disease. We therefore analyzed HBV DNA and the changes in DNA signals after endonuclease digestion in liver tissues taken from 64 patients with hepatitis B surface antigen-positive chronic liver disease. The "active" replication pattern, which included various replicative intermediates, was seen in 36 of 38 (95%) hepatitis B e antigen-seropositive patients. This pattern was also found in 5 of 26 (19%) hepatitis B e antigen-seronegative patients who showed the highest mean serum alanine aminotransferase level (403 +/- 184 mU/ml). Most of them had advanced liver disease. Episomal viral DNA of an "inactive" type having only the supercoiled form was found in 3 patients; they showed the lowest mean serum alanine aminotransferase level (27 +/- 7 mU/ml) and only mild liver disease. As with duck HBV infection, episomal replicative forms of human HBV could be resolved by Southern blot analysis and seem to have clinical implications in human HBV infection.

Adult↗
PubMed1985

Recombinant leukocyte a interferon treatment in patients with chronic hepatitis B virus infection. Pharmacokinetics, tolerance, and biologic effects.

Large doses of recombinant leukocyte A interferon were administered to 20 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis B to study the maximum tolerated dose, its pharmacokinetics, and its antiviral activity. The first group of 5 patients received a constant dose of 36 X 10(6) U/day for 28 consecutive days. When it was well tolerated, the second, third, and fourth groups (5 patients each) received 50, 72, and 100 X 10(6) U/day, respectively. All 20 patients completed the 28-day treatment. Hourly and daily profile of serum interferon level showed a dose-dependent effect with an increasing dosage, and cumulative effects during the treatment. The mean peak serum interferon concentration ranged from 93 U/ml on day 1 in the first group to 1271 U/ml on day 28 in the fourth group. Inhibition of serum deoxyribonucleic acid polymerase activity and hepatitis B virus-deoxyribonucleic acid during the treatment was compared between the groups with low doses (36 and 50 X 10(6) U) and high doses (72 and 100 X 10(6) U). Low doses of interferon suppressed deoxyribonucleic acid polymerase activity to the same extent as did the high doses. Prednisolone withdrawal was combined with interferon in 5 patients. Three patients treated with such combination became seronegative for hepatitis B e antigen during the treatment, whereas all 15 with interferon alone remained seropositive. These results suggest that a maximum antiviral effect of recombinant leukocyte A interferon is below the maximum tolerated doses.

Adult↗
PubMed1985

Duck hepatitis B virus DNA in liver and serum of Chinese ducks: integration of viral DNA in a hepatocellular carcinoma.

The presence of duck hepatitis B virus (DHBV) DNA in liver and serum and its state (integrated vs. free) were studied in 23 ducks from Chi-tung county in China by spot hybridization and Southern blot hybridization, respectively. In 16 of 23 (70%), DHBV DNA was detected in serum and/or in liver tissue. These infected ducks showed a variety of pathological changes including advanced chronic disease in the liver. In contrast, none of the virus-negative ducks had advanced hepatic changes. One DHBV DNA-seropositive duck had a large hepatocellular carcinoma. Southern blot analysis demonstrated integrated DHBV DNA in neoplastic tissue and abundant episomal DHBV DNA in non-neoplastic tissue of the liver. In one noninfected duck with a small adenoma, no viral DNA was detected in tumor or non-neoplastic tissue. The detection of integrated DHBV DNA in hepatocellular carcinoma suggests that DHBV behaves like human and woodchuck hepatitis viruses in relation to chronic liver disease and hepatocarcinogenesis.

Animals↗
PubMed1985

Liver involvement in sickle cell disease.

In an effort to clarify the features of hepatic dysfunction in sickle cell disease, we obtained serial tests of liver function in 100 consecutive patients with sickle cell anemia and in 30 consecutive patients with hemoglobinopathy SC during a five-year period. There were 32 patients with chronic abnormalities in tests of liver function. These abnormal tests were explained by a variety of lesions in 30 cases, and the liver disease remained unexplained in only 2 patients who declined liver biopsy. The diagnoses in these 30 patients included hepatitis, chronic passive congestion, common duct obstruction, alcoholic liver disease, pregnancy, collagen-vascular disease, and sarcoidosis. Evidence for hepatitis B infection was present in 19 of those with sickle cell anemia and in 6 of those with hemoglobinopathy SC. The bilirubin levels in sickle cell anemia appeared to have a trimodal distribution, with six patients exhibiting markedly elevated levels of indirect bilirubin suggesting a difference in bilirubin metabolism. There was no evidence of liver disease in 72 patients with sickle cell anemia, nor in 24 patients with hemoglobinopathy SC, as these patients exhibited only mild elevation of their serum indirect bilirubin levels owing to chronic hemolysis. Intrasinusoidal sickling and Kupffer cell erythrophagocytosis were nearly universal findings at liver biopsy, irrespective of the clinical disorder, and were not related to the degree of liver test abnormalities. Liver and biliary tract dysfunction in sickle cell disease have been attributed to anoxia secondary to sinusoidal obstruction by sickled erythrocytes and Kupffer cell erythrophagocytosis. However, some causes of liver disease in sickle cell patients can be explained by clinical disorders other than the hemoglobinopathy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1985

Early events in duck hepatitis B virus infection. Sequential appearance of viral deoxyribonucleic acid in the liver, pancreas, kidney, and spleen.

Early events in duck hepatitis B virus infection were studied in 1-day-old ducklings following inoculation. Group A ducklings (n = 26) were inoculated intraperitoneally with 10 microliter of infective serum, and group B ducklings (n = 29) were inoculated with 50 microliter. Samples of the serum, liver, pancreas, kidney, and spleen were taken, starting 3 h after inoculation and continuing through the 14th day. In group A, relaxed circular double-stranded deoxyribonucleic acid (DNA) did not appear in serum until day 10, whereas single-stranded DNA, indicative of active replication of the virus, was already demonstrable in the liver on day 6. In group B, single-stranded DNA was first detected in the liver on day 3, and relaxed circular double-stranded DNA became detectable in the liver and serum on day 6. The pancreas started to have single-stranded DNA on day 10 in group A and on day 6 in group B, suggesting active viral replication in this organ soon after it occurred in the liver. In the spleen, relaxed circular double-stranded DNA was detectable when serum became positive for viral DNA, probably due to contamination by serum DNA. However, single-stranded DNA became detectable on day 14 in group A and on day 6 in group B, suggesting a delayed but active viral replication in the constituent tissues of the spleen. These results have demonstrated that active replication of duck hepatitis B virus starts in the liver after infection, and is followed by the pancreas, the kidney, and the spleen. The incubation period is shortened when larger amounts of virus are inoculated, but the sequential occurrence of viral replication in these organs remains the same.

Animals↗
PubMed1985

Infection with delta agent in Japan.

It is estimated that approximately 70 to 80% of the world's HBsAg carriers live in Southeast Asia, but studies of delta infection in this area are still limited. We studied 323 HBsAg seropositive patients in Japan, and 4 (1.2%) of them were found to be positive for anti-delta antibody, with none positive for delta antigen. These four patients did not belong to the known high-risk groups for delta infection. One HBeAg positive female gave birth to a baby girl, and perinatal transmission of hepatitis B virus and delta was successfully blocked by a combination of hepatitis B immunoglobulin and vaccine. This study in the Tokyo-Chiba area showed delta infection, though low in frequency, among ordinary Japanese citizens. It has been reported that delta antigen is highly infectious to HBsAg carriers and that its infection will cause severe liver damage. Once introduced, it could become epidemic among non-drug users in a country where hepatitis B virus infection is endemic. At this moment, the only way of preventing such a disaster appears to be to reduce the number of chronic carriers by interruption of vertical transmission.

Adolescent↗