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Biomedical subjects

Y Uchimura

Publications and source records attributed to Y Uchimura.

At least 19 recordsLinked to original sources

Serum vascular endothelial growth factor levels in various liver diseases.

The clinical significance of circulating vascular endothelial growth factor (VEGF) in patients with various liver diseases was investigated. Twenty-one patients with acute hepatitis (AH), 40 with chronic hepatitis (CH), 34 with cirrhosis (LC), 16 with fulminant hepatitis (FH), 10 with primary biliary cirrhosis (PBC), 12 with autoimmune hepatitis (AIH), and 120 healthy individuals were included. Serum VEGF levels were measured by a chemiluminescence enzyme-linked immunosorbent assay. The mean values of serum VEGF levels in the patients with AH, CH, LC, FH, AIH, PBC, and control were 172.7, 58.0, 44.1, 37.3, 49.7, 74.9, and 65.0 pg/ml, respectively. The patients with AH had a level of serum VEGF significantly higher than that of the control group (P < 0.001). The serum VEGF levels in survivors of FH were significantly increased, but not in the nonsurvivors in the recovery phase compared with the levels on admission (P < 0.05). In the LC patients, serum VEGF levels were significantly lower than those of the control group (P < 0.05). These findings suggest that serum VEGF level may be associated with hepatocyte regeneration grade.

Acute Disease

Two cases of adult varicella accompanied by hepatic dysfunction.

Varicella is a typical acute exanthematous viral infection caused by varicella-zoster virus (VZV). In recently years, as far as hepatic dysfunction caused by viruses other than the hepatitis virus is concerned, there have been a few reports on hepatic dysfunction accompanying varicella following organ transplantation of Europe and America and another report on an immunocompromized adult following treatment for Systemic lupus erythematosis (SLE) in Japan. Nonetheless, we searched the MEDLINE and J MEDICINE listing the publications between 1986 and 1996 and found one report on healthy adults with varicella accompanied by hepatic dysfunction in Europe and America and two reports in Japan. Only Noguchi et al. dealt with the findings of liver biopsy. We examined two healthy adults with varicella and mild-to-moderate hepatic dysfunction, and referred to the results of their liver biopsies. The present paper discusses this issue, citing some references.

Adult

Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan.

Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.

Adolescent

Transmission routes and clinical courses in sporadic acute hepatitis C.

Between March 1994 and March 1996 we studied transmission routes and clinical courses in eight patients with sporadic acute hepatitis C (two men, six women). Of the eight patients, three were treated for another illness 1-2 months before the onset of hepatitis, one was a parenteral drug abuser, one had an accidental needlestick injury and two had sexual contact with a partner with chronic hepatitis C virus (HCV) infection. Clinical courses included four women whose HCV RNA and alanine aminotransferase (ALT) became persistently negative without treatment, and four men and two women with the same results following interferon (IFN) treatment. It is thought that IFN therapy may prevent the progression to chronic liver disease. Results from this study might be useful in the future management of patients with sporadic acute hepatitis C.

Acute Disease

Effects of interferon alpha 2a on incidence of hepatocellular carcinoma in chronic active hepatitis without cirrhosis. Hepatitis Treatment Study Group.

To determine the incidence of hepatocellular carcinoma among patients with chronic hepatitis C who received interferon (IFN) therapy, 63 patients with chronic hepatitis C who underwent IFN therapy (IFN alpha 2a 9 x 10(6) IU daily for 2 weeks and followed 9 x 10(6) IU three times weekly for 14 weeks) from January to December 1992, were studied. Selection criteria were as follows: within six months before IFN therapy patients were diagnosed with chronic active hepatitis without cirrhosis by hepatic histological examination, and were hepatitis C virus antibody positive. Furthermore, patients had records of follow-up liver function tests (once a month) for more than six months after IFN therapy completion, and of ultrasound scanning (once in three to four months) before and for at least more than six months after the therapy completion. An average period of observation was 2.7 years (0.6 to 3.8 years). Twenty five of 63 patients (39.7%) returned to normal values of serum ALT, whereas 38 of 63 (60.3%) still showed abnormal values at six months after IFN therapy completion. Nine of 63 (14.2%) and 6/63 (9.5%) developed cirrhosis and hepatocellular carcinoma, respectively. All patients who developed cirrhosis and hepatocellular carcinoma were from those (n = 38) that showed abnormal ALT values after therapy completion. The five of six patients that progressed to hepatocellular carcinoma were associated with cirrhosis. No patients who returned to normal ALT values developed hepatocellular carcinoma during the period of observation. These results suggest that IFN therapy is effective to prevent the development of hepatocellular carcinoma.

Adult

A case of malignant lymphoma with hemophagocytic syndrome presenting as hepatic failure.

We report the case of a 50-year-old female with malignant lymphoma presenting hemophagocytic syndrome and liver failure. She developed high fever, marked jaundice, and progressive liver failure, followed by evidence of disseminated intravascular coagulation (DIC). The course was complicated by severe hepatitis and the patient died six days after admission. Pathological diagnosis on autopsy specimens of the lung hilar lymph nodes was non-Hodgkin's T cell lymphoma, of the diffuse small cell type. Histopathologic examination of the liver demonstrated diffuse liver cell destruction with prominent T lymphocyte infiltration in the portal and periportal area. In addition to marked lymphoma cell infiltration, hemophagocytosis by prominent infiltrative macrophages was observed in various organs, such as the liver and bone marrow, indicating the hemophagocytic syndrome. The hemophagocytic syndrome characterized in the present case may have been responsible for the extremely rapid and fulminant course.

Fatal Outcome

Laparoscopic pylorus-preserving gastrectomy with intracorporeal hand-sewn anastomosis.

To prevent stapled stenosis after laparoscopic local gastric resection by using autosuturing devices, we developed a technique for laparoscopic pylorus-preserving gastrectomy with intracorporeal hand-sewn anastomosis. We describe this procedure and present two case reports. The intracorporeal hand-sewn anastomotic technique is an important advance in the field of minimally invasive laparoscopic surgery.

Aged

Hepatic iron stainings in chronic hepatitis C patients with low HCV RNA levels: a predictive marker for IFN therapy.

OBJECTIVES: Interferon (IFN) therapy is ineffective in about 20-30% of chronic hepatitis C (CH-C) patients who have low HCV RNA levels. Besides the serum HCV RNA level or HCV genotype, hepatic iron concentrations are thought to be correlated with the subsequent response to IFN therapy. Our objective in the present study was to evaluate serum iron, ferritin, and hepatic iron staining in patients with low HCV RNA levels, as predictive markers for IFN therapy. METHODS: We evaluated 75 CH-C patients whose serum HCV RNA levels were below 1 million genome equivalent (mEq)/ml as shown by a bDNA assay. RESULTS: There were no significant differences in age, sex, serum aminotransferase levels, or serum iron concentrations between responders and nonresponders. The total iron scores (TIS) were significantly higher in responders (p < 0.01). The TIS was an independent factor relating to the response to IFN therapy by multivariate analysis (p = 0.0062). The TIS significantly correlated with serum ferritin levels (r = 0.637, p < 0.001), but not with any other parameter. bi] CONCLUSIONS: Among CH-C patients within the limits of low HCV RNA levels, TIS of the liver may be used as a predictive marker for IFN therapy.

Adult

Hepatitis C virus infection in patients with clinically diagnosed alcoholic liver diseases.

To determine the incidence of hepatitis C virus (HCV) infection in patients with alcoholic liver disease (ALD), serum samples from 252 patients with ALD were tested for anti-HCV and HCV RNA. Serial sera of these patients were collected and stored under optimal conditions to allow exact quantification of HCV RNA. Fifteen patients who visited our hospital during the same period of time with chronic HCV infections served as controls. In those with ALD, anti-HCV and HCV RNA were positive in 55.5% and 41.2%, respectively. Patients with histologically diagnosed chronic hepatitis and hepatocellular carcinoma had much higher prevalence rates of HCV RNA (84% and 100%, respectively) compared to those with fatty liver (4.3%), hepatic fibrosis (10.1%) and alcoholic hepatitis (22.2%) (P < 0.01). Although no difference in serum HCV RNA levels was observed between the patients with both ALD and chronic HCV infection and those with chronic HCV infection alone, HCV RNA levels significantly (10-fold) dropped after abstinence in nearly half of the patients (P < 0.01). These data indicate that HCV infection in patients with ALD promotes progression of liver disease, and abstinence from alcohol is associated with a reduction in serum HCV RNA levels.

Adult

Sequential interferon-alpha and beta treatment in patients with chronic hepatitis C.

To assess the effectiveness and side effects of sequential interferon (IFN)-alpha and beta treatment for patients with chronic hepatitis C, 25 patients were enrolled in a trial of this regimen. The patients were given 6 million units (MU) of natural human INF-beta daily for 2 weeks followed by 6 MU of natural human IFN-alpha three times a week for 10 to 22 weeks. Serum alanine aminotransferase (ALT) levels normalized for at least 24 weeks in 10 patients (40%), of whom 4 (40%) had no detectable serum hepatitis C virus (HCV) RNA. Three variables were significant in predicting a sustained response: a low serum HCV RNA level, a low Knodell's fibrosis score, and a low indocyanine green retention rate at 15 minutes. Elevated serum ALT and proteinurea were observed with IFN-beta treatment but these side effects were mild and disappeared when INF-beta treatment ended. While all patients completed the entire regimen, we concluded that sequential IFN-alpha and beta treatment provides no additional antiviral effects in chronic hepatitis C.

Alanine Transaminase

An experimental animal model of primary biliary cirrhosis induced by lipopolysaccharide and pyruvate dehydrogenase.

Previously, we found that the antibody titer belonging to the IgM class produced against the bacterial antigen (Lipid A) was elevated in sera from patients with primary biliary cirrhosis (PBC). On the other hand, the targets of the mitochondrial autoantibodies have been identified as being components of the pyruvate dehydrogenase complex (PDH). We tried to produce an experimental animal model for the investigation of the association between hepatic bile duct alteration and bacterial infection. Female C57/BL mice, aged 4 weeks, were used. An emulsion consisting of lipopolysaccharide (LPS) derived from Salmonella minnesota Re595, PDH, and Freund's adjuvant was prepared. This emulsion was subcutaneously injected on the back of the mice. The mice were divided into a control group (n = 5), a group given LPS (n = 5) alone, those given PDH alone (n = 5), and those given a combination of LPS and PDH (n = 5). The antigens were administered once a week every week with a maximum duration of administration of 24 weeks. The serum levels of IgM after 24 weeks in the LPS and LPS + PDH groups were 2.5 times higher than those in the control and PDH groups. The light microscopic findings of liver tissue revealed that infiltration of lymphocytes and plasma cells in the portal area, proliferation of the bile duct, and degeneration of the biliary epithelial cells were more prominent in the PDH and LPS + PDH groups than in the other groups. These results indicate that our animal model may be useful in investing the pathogenesis of PBC.

Animals

A patient with chronic hepatitis C and a history of abuse of analeptic drugs, who showed hallucination and delusion with interferon administration.

We experienced a case of chronic hepatitis type C accompanied with hallucination and delusion induced by interferon (IFN) therapy positive. The case was a 47-year-old male, whose laboratory data showed positive for anti-Hepatitis C Virus (HCV) and elevated transaminase level. He was treated with 6 MU/day of natural-type IFN-alpha (HLBI). Sleeplessness and delusions of persecution developed about 2 months after the start of IFN therapy. The interview of the psychiatrist disclosed that the patient had a history of addiction to drugs, and these psychiatric symptoms were diagnosed as being of "the flashback phenomenon." These side effects were improved after the administration of psychotropics and it was suggested that we had to take care of the development of flashback phenomenon during the treatment of IFN in cases of chronic hepatitis with a history of addiction to drugs.

Delusions

A histopathological study of alcoholics with chronic HCV infection: comparison with chronic hepatitis C and alcoholic liver disease.

To clarify the relationship between hepatitis C virus infection and excessive alcohol intake, we carried out histological examination of the liver in 46 alcoholics with chronic hepatitis C virus infection and compared the findings in 55 patients with chronic hepatitis C, 38 with alcoholic liver disease, and 27 with chronic hepatitis B. The majority of alcoholics with chronic hepatitis C virus infection displayed virus-related histological changes very similar to those in chronic hepatitis C, including frequent lymphoid follicles (34.7%) or aggregates (93.3%) in the portal tracts, mild necroinflammatory change (76.1%) in the parenchyma, and lymphocytosis in sinusoids (83.7%). Liver cell dysplasia and irregular regenerative activity of hepatocytes were rarely observed. The effects of alcohol on the liver were found to be minimal in the majority. These findings could suggest that the hepatic injury in the majority of alcoholics with chronic hepatitis C virus infection in Japan is due to persistent hepatitis C virus infection rather than to alcoholic injury. In addition, our study disclosed that the perivenular fibrosis which is designated as a histological characteristic of alcoholic liver disease is frequently observed in chronic hepatitis C. These similarities suggest that a similar fibrogenesis is present in chronic hepatitis C and alcoholic liver disease.

Adult

Decrease of interferon-induced 2',5'-oligoadenylate synthetase activity in cirrhotic rat liver.

We evaluated the effect of hepatic fibrosis on the induction of hepatic 2',5'-oligoadenylate synthetase (2-5AS) by interferon (IFN) in a rat model of liver cirrhosis, induced with thioacetamide. Although there was no difference in serum 2-5AS activity between the control and cirrhotic rats given murine IFN, 2-5AS activity in the liver homogenates of cirrhotic rats was significantly lower than in the controls (105 +/- 18.5 vs. 171 +/- 10.2 pmol/micrograms, p < 0.01). These results suggested that hepatic fibrosis attenuated the effect of IFN and one of the reasons for this may be the decreased induction of hepatic 2-5AS activity after IFN administration in the presence of a cirrhotic liver.

2',5'-Oligoadenylate Synthetase

A case of acute exacerbation of chronic hepatitis B accompanied by antibody to HBeAg with remission of liver damage after long-term treatment with interferon.

The patient was a 47-year-old female with chronic hepatitis B having antibody to HBe antigen (HBeAg). She was admitted to our hospital in March, 1994, because of acute exacerbation of chronic hepatitis B. Laboratory data revealed the elevated serum transaminase and DNA-polymerase levels, and decreased prothrombin activity. The histological examination of the liver showed chronic active hepatitis with severe hepatic necrosis. Point mutation of the precore region of HBV-DNA (pre-C mutant) was observed in clones from this case by polymerase chain reaction method. The patient was treated with recombinant interferon alpha-2a 9 MU daily for 2 weeks and thereafter 3 times weekly for 6 months. After interferon therapy, the pre-C mutant disappeared with the improvement of transaminase levels and prothrombin activity. These findings suggest the possibility that long-term treatment with interferon therapy is effective for the acute exacerbation of chronic hepatitis B accompanied by antibody to HBeAg.

Chronic Disease

[Application of AmpliType PM kit to forensic sciences].

Five genetic loci, low density lipoprotein (LDLR), glycophorin A (GYPA), hemoglobin G gammaglobin (HBGG), D7S8 and group specific component (GC), can be identified in a single step by the AmpliType PM kit. The kit uses multiplex PCR amplification and hybridization by a reverse dot blot method. To introduce the new marker system in forensic caseworks in Japan, a relevant Japanese population database must be established. In this context, the allele frequencies of the 5 genetic loci were determined for 246 unrelated Japanese. The allele frequencies were LDLR*A 0.173, LDLR*B 0.827, GYPA*A 0.528, GYPA*B 0.472, HBGG*A 0.352, HBGG*B 0.648, HBGG*C 0.000, D7S8*A 0.612, D7S8*B 0.388, GC*A 0.258, GC*B 0.504 and GC*C 0.238, respectively. In all 5 systems, the genotype frequencies are in good accordance with the Hardy-Weinberg expectations. The power of discrimination (PD) of LDLR, GYPA, HBGG, D7S8 and GC were 0.449, 0.624, 0.600, 0.612 and 0.788, respectively, resulting in a combined PD of 0.993, while these 5 DNA types could be determined from slaiva and semen. And the GYPA or GC genotypes were observed to have good relations with the MN and serum Gc phenotypes. The AmpliType PM kit was confirmed to be a reliable DNA typing system which was well suited for use in forensic sciences.

Alleles