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Biomedical subjects

Y Uchimura

Publications and source records attributed to Y Uchimura.

At least 19 recordsLinked to original sources

Full-sized RanBPM cDNA encodes a protein possessing a long stretch of proline and glutamine within the N-terminal region, comprising a large protein complex.

Previously isolated RanBPM, a Ran-binding protein in the microtubule-organizing center, which had been thought to play a role in Ran-stimulated microtubule assembly, turned out to be a truncated protein. To clarify the function of RanBPM, we cloned the full-sized RanBPM cDNA that encodes a 90 kDa protein, compared to the previously isolated cDNA that encoded a 55 kDa protein. The newly cloned 5' coding region contains a great number of cytidine and guanidine nucleotides, like the CpG island. Thus, full-sized RanBPM cDNA encodes a long stretch of proline and glutamine residues in the N-terminal region. It comprises a protein complex of more than 670 kDa. Ran was detected in this complex when RanBPM and Ran were both ectopically expressed. New antibodies to RanBPM were prepared against three different regions of RanBPM. All of them detected a 90 kDa protein that is predominantly localized both in the nucleus and in the cytoplasmic region surrounding the centrosome, but none of them stained the centrosome. In this context, our previous notion that RanBPM is a centrosomal protein should be discarded. RanBPM is well conserved in the animal kingdom. It may play an important role in uncovering Ran-dependent nuclear events.

Adaptor Proteins, Signal Transducing↗

Surfactant-lactoperoxidase complex catalytically active in organic media.

A surfactant-lactoperoxidase (LPO) complex catalytically active in organic solvents was developed by the emulsion coating method. The oxidation of 2,6-dimethoxyphenol (2,6-DMP) was conducted by the surfactant-LPO complex in organic media. The LPO complex efficiently catalyzed the oxidation of 2,6-DMP in various organic solvents, although lyophilized LPO did not display the catalytic activity at all. To optimize the preparation and reaction conditions for the surfactant-LPO complex, we examined the effects of pH value in the water pools of W/O emulsions, kinds of oxidants, and the nature of organic solvents on the oxidation reaction. Its optimum activity was obtained when the pH value of the aqueous enzyme solution was adjusted to ca. 8 at the preparation stage. The LPO complex exhibited the highest catalytic activity in chloroform when H(2)O(2) was employed as the oxidant. Furthermore, the storage stability of the surfactant-LPO complex was far better than that of the surfactant-horseradish peroxidase complex. This high storage stability of the LPO complex will be a benefit for industrial usage of peroxidases.

Journal Article↗

Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis.

BACKGROUND: To identify injured cells in the liver of patients with primary biliary cirrhosis (PBC) and to determine the effects of ursodeoxycholic acid (UDCA) on these cells, we examined the cellular expression of heat shock proteins (HSPs) in PBC both before and after treatment with UDCA. METHODS: Expression of HSP70 and ubiquitin in PBC livers (n=34) was evaluated immunohistochemically as well as by immunoblot analysis, and compared with chronic viral hepatitis type C (n= 9), primary sclerosing cholangitis (n=8), and controls (n=7). RESULTS: Immunoblot analysis demonstrated a marked expression of HSP70 and ubiquitin in PBC. Immunohistochemical staining for both HSP70 and ubiquitin was observed to be strong in biliary epithelial cells (BECs) and moderate in both hepatocytes and arteries in PBC. Cellular labelling rates for HSP70 and ubiquitin of bile ducts in PBC were significantly higher (p<0.01) than those in chronic viral hepatitis type C, primary sclerosing cholangitis, or controls. The labelling rates for HSP70 and ubiquitin in bile ducts and in hepatocytes were significantly decreased (p<0.01) after treatment with UDCA in PBC. CONCLUSIONS: The present data suggest that BECs and hepatocytes significantly express HSPs even in the early stages of PBC, and that UDCA treatment significantly improves their condition. The immunohistochemical evaluation of HSPs is a valid and sensitive means to identify injured cells in PBC.

Adult↗

Erythropoietic protoporphyria with fatal liver failure.

A 33-year-old woman with a history of photosensitivity, persistent abdominal pain, and liver dysfunction was admitted to our department because of abdominal pain and progression of liver dysfunction. On admission, levels of protoporphyrin and coproporphyrin within erythrocytes were markedly increased. Autofluorescent erythrocytes were also detected, leading to a diagnosis of erythropoietic protoporphyria. A liver biopsy specimen revealed cirrhosis with dark brown granules filling hepatocytes, bile canaliculi, and bile ductules. Transfusion of washed erythrocytes, hemodialysis, and administration of cholestyramine and beta-carotene transiently improved levels of porphyrins and liver function. The patient died of rupture of esophageal varices followed by multiple organ failure. However, the treatments were believed to have extended survival.

Adult↗

Intraspousal transmission of GB virus C/hepatitis G virus in an hepatitis C virus hyperendemic area in Japan.

OBJECTIVE: An immunoassay for antibodies against an hepatitis G virus (HGV) protein (anti-E2) was recently developed that might serve as a useful marker for diagnosing recovery from HGV infection. METHODS: We investigated the intraspousal transmission of GB virus C/hepatitis G virus (GBV-C/HGV) using both reverse transcription hemipolymerase chain reaction (RT-hemi-PCR for the 5' untranslated region) and a recently developed anti-E2. RESULTS: Thirty-two GBV-C/HGV-infected index subjects were selected from an hepatitis C virus hyperendemic area in Japan. Of the 32 subjects, seven (6.4%) were GBV-C/HGV RNA-positive, 24 (21.8%) were anti-E2-positive, and one (0.9%) was both GBV-C/HGV RNA- and anti-E2-positive. Among the 32 spouses of these subjects, GBV-C/HGV RNA, anti-E2, and both GBV-C/HGV RNA and anti-E2 positivity were detected in 0, 6, (18.8%), and one (3.1%) spouses, respectively (the total prevalence of GBV-C/HGV was 7 spouses [21.9%]). Thus, the intraspousal transmission of GBV-C/HGV was undeniable in these seven couples. The respective positive rates of 175 sex- and age-matched controls were 7 (4.0%), 26 (14.9%), and 0 (the total prevalence of GBV-C/HGV was 34 [19.4%]). No significant difference in positive rates was observed between the subjects/spouses and the controls. Five spouses among the seven couples who were positive for any of GBV-C/HGV markers had parenteral risk factors such as blood transfusion, acupuncture, and major surgery. CONCLUSION: Based on these observations, we cannot draw a definitive conclusion that intraspousal transmission of GBV-C/HGV had occurred among these seven couples.

Aged↗

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↗

Unusual accumulation of glycogen in liver parenchymal cells in a patient with anorexia nervosa.

Anorexia nervosa is an eating disorder characterized by a fear of weight gain and a preoccupation with body image. Although hepatic involvement has been reported in patients with anorexia nervosa, the mechanism is not fully understood. We describe a patient with anorexia nervosa with liver function abnormalities. Light and electron microscopic observations revealed a remarkable accumulation of glycogen in hepatocytes. These results suggest that adaptive responses to starvation may alter carbohydrate metabolism in patients with anorexia nervosa.

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↗