Search PubMed⌕ Search

Biomedical subjects

M Nakamuta

Publications and source records attributed to M Nakamuta.

64 records · Page 4Linked to original sources

Hepatic epithelioid hemangioendothelioma.

Epithelioid hemangioendothelioma (EHE) is a rare neoplasm of vascular origin with unpredictable malignant potential. We describe two patients with primary EHE of the liver and review 34 cases previously published in Japan and compare them with those in Western countries. The clinical aspects of EHE and relevant treatment results in Japanese patients were similar to those found in Western countries, the exception being the matter of difference in incidence between genders. Although this tumor type has been reported to be more frequent among women, there was no significant difference in incidence between men and women. Hepatic EHE generally behaves as a low-grade malignant tumor with a slow progression phenotype; however, this disease seems to be resistant to chemotherapy and to be lethal in some cases. Surgical resection or liver transplantation is recommended after rapid diagnosis by radiologic examination and histologic findings, including positive staining of tumor cells for factor VIII-related antigen.

Adult↗

Oral contraceptive-dependent growth of focal nodular hyperplasia.

A 22 year old woman was incidentally found to have a hepatic small haemangioma-like mass, measuring 1.4 cm in diameter, by an ultrasonographic examination. The mass demonstrated no change in size or appearance for 6 months until the patient began to take oral contraceptives. Eventually, the mass increased to 2.0 cm in diameter after using oral contraceptives for 6 months. A histological examination suggested the mass to be typical focal nodular hyperplasia, and not hepatic adenoma. There was no further change in either size or appearance in the ensuing 1 year after the discontinuation of oral contraceptives.

Adult↗

Rise of plasma myeloperoxidase during interferon therapy.

The plasma myeloperoxidase (MPO) level was evaluated using a specific radio-immunoassay (RIA) for MPO in alpha 2b-interferon (IFN)-treated patients with chronic viral hepatitis. The plasma MPO was checked before and after the initial 2 weeks use of IFN at a dose of 6 x 10(6) U/day. The mean concentration of plasma MPO was found to be markedly higher after IFN therapy than that before the therapy (421.7 +/- 34.3 vs 242.9 +/- 23.0 ng/mL, P < 0.001). The plasma MPO negatively correlated with the granulocyte count (r = -0.37, P < 0.02) and the platelet count (r = 0.49, P < 0.01, while it positively correlated with serum alkaline phosphatase (ALP; r = 0.41, P < 0.03). The plasma MPO also showed a strong correlation with plasma polymorphonuclear granulocyte elastase (PMN elastase; r = 0.73, P < 0.001). Our study thus suggests that the increased release of MPO from destroyed granulocytes is responsible for the high concentrations of the plasma MPO in patients during IFN therapy, because the plasma MPO, PMN elastase and ALP abundant in granulocytes all increased in spite of a decrease in the granulocyte count. Granulocytopenia during IFN therapy may therefore be due to the increased destruction of granulocytes in addition to a direct suppression of the bone marrow by IFN.

Agranulocytosis↗

Clinical significance of urinary N1,N12-diacetylspermine levels in patients with hepatocellular carcinoma.

BACKGROUND/AIM: N1,N12-diacetylspermine (DiAcSpm), a diacetylpolyamine which was recently identified in urine, appeared to be a useful tumor marker for urogenital cancers. Here we examined the clinical significance of urinary DiAcSpm as a tumor marker for hepatocellular carcinoma (HCC). METHODS: Urine samples were collected from patients with HCC and benign liver diseases. Urinary levels of DiAcSpm were measured by ELISA, which was newly developed in order to analyze large numbers of samples. RESULTS: The appropriate threshold value was set at 325 nM/g x creatinine. The sensitivity of the DiAcSpm assay for HCC was 65.5% and the specificity calculated between HCC and liver cirrhosis was 76.0%. The percentage of DiAcSpm-positive HCC patients was similar to that for AFP or PIVKA-II. At more advanced clinical stages, the positive percentage of these three markers increased but the DiAcSpm levels appeared to move independently of AFP and PIVKA-II. In HCC patients, the DiAcSpm levels reflected the progression of disease or the effect of treatment. CONCLUSIONS: DiAcSpm levels were found to reflect the severity, activity or viability of HCC. Urinary DiAcSpm can therefore be considered one of the useful indexes for patients with HCC.

Biomarkers↗

Predictors of the efficacy of intravenous natural interferon-beta treatment in chronic hepatitis C.

INTRODUCTION: Several pretreatment factors have been reported to be useful in predicting patients with a high probability for a sustained response to IFN-alpha treatment, however, predictors of the efficacy of interferon-beta treatment in chronic hepatitis C have not been fully assessed. MATERIAL AND METHODS: To clarify this issue, a prospective study of 52 patients with chronic hepatitis C was conducted. Patients were treated with human natural interferon-beta by drip infusion at doses of 6 MU/day for 8 weeks. The following characteristics were compared between patients with sustained response (SR) and no response (NR): gender, age, source of HCV infection, mean pretreatment serum ALT levels, liver histology, pretreatment serum HCV-RNA levels and HCV genotype. RESULTS: Seventeen of 52 patients (32.7%) demonstrated SR. The proportion of patients with undetectable HCV-RNA levels determined by branched DNA assay (< 0.5 x 10(6) eq/ml) was higher in patients with SR than in those with NR (88.2% vs. 22.9%; p = 0.0001). Pretreatment HCV RNA levels determined by multicyclic reverse transcriptase polymerase chain reaction were lower in patients with SR than in those with NR (10(5.1 +/- 1.5) vs. 10(7.1 +/- 1.3) copies/ml; p = 0.0001). The rate of SR was higher in patients with genotype 2a or 2b than in genotype 1b (43.8% vs. 15.0%; p = 0.0382). Multivariate stepwise logistic regression analysis showed that a younger age and low pretreatment serum levels of HCV RNA were independent predictors of SR to treatment. This prospective study demonstrated that a younger age, low pretreatment viral load and HCV genotype 2a or 2b were factors influencing the SR to interferon-beta treatment, but a younger age and low pretreatment viral load were most important predictors of the efficacy of the treatment.

Adolescent↗

Beta-lipoproteins influence the serum level of hepatitis C virus.

Low density lipoprotein receptor (LDLR) has been proposed as a candidate receptor for hepatitis C virus (HCV). According to previous reports, free beta-lipoproteins in a human serum may regulate the rate of hepatocyte infection by competing with the virus. Therefore, serum HCV levels should be regulated by the rise and fall of serum beta-lipoproteins since the infection rate of virions influences HCV replication in hepatocytes and release of virions by hepatocytes. In this study, we examined the relationship between serum beta-lipoproteins and HCV-antigen (Ag) levels in patients with chronic type C hepatitis. Patients were selected based on strict criteria to eliminate other factors that might influence serum HCV levels. Serum concentrations of beta-lipoproteins and HCV-Ag were measured two or more times within 3 months for each patient. The result showed that HCV-Ag levels were negatively correlated with the increased beta-lipoproteins. The results support the concept that LDLR is a HCV receptor and that beta-lipoproteins competitively inhibit the infection of hepatocytes with HCV through the LDLR.

Binding, Competitive↗

Analysis of HBs antigen negative variant of hepatitis B virus: unique substitutions, Glu129 to Asp and Gly145 to Ala in the surface antigen gene.

We analyzed the surface gene (S gene) of a hepatitis B virus (HBV) isolate with mutations of envelope protein that rendered it undetectable by both a monoclonal hepatitis B surface antigen (HBsAg) enzyme-linked immunosorbent assay (ELISA) and polyclonal HBsAg radioimmunoassay (RIA). Sequencing of independently cloned products of HBV polymerase chain reaction revealed several point mutations within the S gene. Rare substitution was identified both at positions 129 (glutamine to asparagine) and at position 145 (glycine to alanine) in the 'a' determinant region, which is considered to be within a larger antigenic area known as the major hydrophilic region (MHR). A computer-assisted analysis of protein secondary structure could not find any significant difference between this mutant and wild-type HBsAg. However, the substitution of substitution glycine to alanine at position 129 introduce a putative glycosylation site (Asn-Gly-Thr), which may interfere with the antigenicity of HbsAg. Also, HBV variant with substitution at position 145 (Gly to Ala) has been recently reported to be antigenically altered and to show impaired recognition by polyclonal hepatitis B hyperimmune globulin in vitro. These genetic mutations in the S gene inside MHR may allow to escape detection by standard HBsAg assays.

Amino Acid Sequence↗

Serum leptin levels in patients with nonalcoholic chronic liver disease.

BACKGROUND/AIMS: The elevated serum leptin level of patients with alcoholic cirrhosis has been reported, however, the precise mechanism is still unknown. Leptin expression and protein synthesis have also been detected in activated hepatic stellate cells in cell cultures, which play a major role in hepatic fibrosis. We evaluated the serum leptin levels of patients with nonalcoholic liver diseases including cirrhosis and chronic hepatitis. We also investigated the hepatic clearance of leptin by determining the serum leptin level in blood samples obtained from the portal and hepatic veins. METHODOLOGY: The serum leptin level of 44 patients with nonalcoholic chronic liver disease (male/female = 21/23, cirrhosis/chronic hepatitis = 30/14) and 40 control subjects (male/female = 20/20) was determined in blood samples obtained from the antecubital vein by enzyme-linked immunosorbent assay. We also assessed the relationship between the leptin level and various biochemical tests of liver function. Additionally, we determined the leptin levels in the portal and the hepatic venous blood (nonalcoholic cirrhosis = 10, nonhepatic disease = 4). RESULTS: There were positive correlations between the serum leptin level and body mass index among males and among females in the liver disease group and in the control group. However, the serum leptin level of the liver disease group and control group did not differ significantly. Among the 44 liver disease patients, only the serum cholesterol level was significantly correlated with the serum leptin level after adjusting for sex and body mass index by multiple regression analysis. Furthermore, the leptin level in hepatic venous blood was significantly lower than that in portal venous blood. However, the ratio of [leptin level in hepatic venous blood]/[leptin level in portal venous blood] in the cirrhosis group, and that in the nonhepatic disease group, did not significantly differ. CONCLUSIONS: The serum leptin level of patients with nonalcoholic liver diseases is not elevated. On the other hand, the serum leptin level of patients with alcoholic cirrhosis has been reported to be elevated. The difference in the serum leptin level of patients with nonalcoholic liver disease and that of patients with alcoholic cirrhosis may be due to a difference in factors such as the levels of cytokines or sex steroids, and/or nutrition. Furthermore, it is likely that leptin is cleared in part by the portosystemic circulation through the liver.

Adult↗

Primary hepatic carcinoid tumor: case report and review of 53 cases.

BACKGROUND: Primary hepatic carcinoid tumor (PHCT) is a extremely rare. The authors describe a patient with PHCT and review previously published cases of the disease. CASE REPORT: A 75-year-old man, presenting with weight loss and pain in the right upper abdomen, had multiple masses in both lobes of the liver. He was diagnosed as PHCT by radiological examination, laboratory findings with high levels of 5-hydroxyindoleacetic acid (5-HIAA) in the serum and urine, and histological findings including positive staining of tumor cells for Grimelius and chromogranin A. The patient received totally transcatheter arterial chemoembolization (TACE) five times over 27 months; this treatment provided excellent palliation and caused a decrease in urinary 5-HIAA levels. Fifty-three cases of PHCT have been reported in the English-language literature. RESULTS: Analysis of these published cases revealed that PHCT occurs in the middle age (mean age = 48.2 years) and is more frequent in females (males/females = 20/33 cases). Of the symptomatic patients, the major findings is abdominal pain, fullness, and/or a palpable mass (56% of symptomatic patients). In contrast, only 2 cases out of 53 presented with symptoms of typical carcinoid syndrome. In most cases, PHCT was detected as a hypervascular lesion by radiological examination. By histological analysis, 80% and 84% of the cases were positive for Grimelius silver stain and immunohistochemically positive for chromogranin A, respectively. Surgical resection is the treatment primarily recommended with an 18% of recurrence rate and a 74% of a survival rate after 5 years. For unresectable and recurrent cases, TACE may be recommended.

Aged↗