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S Nambu

Publications and source records attributed to S Nambu.

At least 19 recordsLinked to original sources
PubMed1999

Functional B-cell response in intrahepatic lymphoid follicles in chronic hepatitis C.

Intrahepatic lymphoid follicle (ILF) formation is one of the most characteristic and commonly observed histological features in patients with chronic hepatitis C. However, little is known regarding whether follicles in the liver belong to functional lymphoid tissues, where B cells are activated, differentiated, and proliferated, or if the lymphocytes are merely infiltrated after recruitment from the secondary lymphoid organs. To ascertain this possibility, we examined the expression of markers for B-cell activation, differentiation, and proliferation in ILFs in patients with chronic hepatitis C using surgically resected specimens, and compared them with specimens of perihepatic lymph nodes by an immunohistochemical technique. Germinal center (GC) formation in the ILFs was frequently found in HCV-positive cases. The distribution of immunoglobulin M (IgM)-, IgD-, and IgG-positive cells and the expression patterns of Ki-67, CD23, or bcl-2 and bcl-6 gene products in the follicles with GC formation in the liver of patients with chronic hepatitis C were similar to those of lymph nodes, indicating that B cells are activated, proliferated, and differentiated in the ILFs with GC formation in patients with chronic hepatitis C. Oligoclonal expansion of B cells in the livers with ILFs was confirmed by an analysis of immunoglobulin heavy chain (IgH) gene rearrangement determined by polymerase chain reaction (PCR). These data strongly suggest that ILFs with GC formation, which are frequently found in patients with chronic hepatitis C, may functionally be the same as those found in lymph nodes with respect to B-cell expansion and maturation.

Adult↗
PubMed1999

[Method for remnant lipoproteins--quantitative analysis of serum remnant-like particle cholesterol (RLP-C)].

The important role of remnant lipoprotein, which is linked up to serum insulin, in the development of atherosclerosis is well known. So, measurement of remnant has a benefit as the indicator of cardiovascular disease-risk. Recently, Nakajima et al have developed a simple, rapid assay method, using a immunoaffinity gel mixture of anti-apo B-100 and anti-apo A1 monoclonal antibodies coupled with Sepharose 4B. The apoprotein composition of RLP which is unbound with mixed gel is as similar to apo-E rich VLDL. Clinical significance of RLP-C has been already indicated by many reports.

Apolipoproteins↗
PubMed1998

A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in vivo growth of murine and human hepatoma: implication for immunotherapy of human hepatocellular carcinoma.

Although treatment for hepatocellular carcinoma (HCC) has recently improved, most patients still relapse and die from this disease. The development of new therapeutic and preventive strategies for HCC is, therefore, required. A novel mutant protein (mutein) of human tumor necrosis factor alfa (TNF-alpha mutein F4614, 1SSSRGDSD... 29V ... 155L) was developed to decrease several adverse effects of TNF-alpha. F4614 is known to lack hypotensive effects of human TNF-alpha without losing its anti-tumor effect in mice transplanted with Meth-A sarcoma. Our study investigated the anti-tumor effects of F4614 against hepatoma cells in vitro and in vivo. F4614 significantly inhibited growth of all four tumor cells in vitro. A murine hepatoma cell line, MH134, when incubated in the presence of F4614, exhibited upregulation of surface major histocompatibility complex (MHC) class-I, intercellular adhesion molecule-1 (ICAM-1) and B7-1 molecules, and a decreased proportion of cells in the G2/M phase of the cell cycle. In addition, F4614 induced apoptosis in a significant number of MH134 cells. TNF-alpha and F4614 (5 microg/mouse daily for 5 days) showed similar anti-tumor activities in syngeneic MH134-bearing mice and heterogeneic PLC/PRF/5-bearing athymic nude mice. Intratumoral injection of F4614 or TNF-alpha was more effective than intravenous injection. Immunohistochemical analysis of the tumors treated by F4614 revealed that tumors were surrounded with a large number of Mac-1+ cells and a small number of CD4+ and CD8+ T cells; that suggests that intratumoral injection of F4614 elicited host immunoreactions. Thus, F4614 may be a new strategy for immunotherapy of HCC.

Animals↗
PubMed1998

Case report: intrahepatic portal-hepatic venous shunts associated with a huge pelvic leiomyoma.

We present a case of portal-systemic encephalopathy due to intrahepatic multiple portal-hepatic venous shunts. A 71-year-old woman was admitted to our hospital because of recurrent episodes of disturbed consciousness. She showed no clinical signs of portal hypertension. Liver function was normal, except for an indocyanine green retention rate of 34% at 15 min and blood ammonia level of 282 microg/dL. Portal venography revealed dilatation of the portal vein and multiple portal-hepatic venous shunts, and a liver biopsy specimen revealed almost normal liver. Further clinical examination revealed a huge pelvic tumour. At laparotomy, two dilated veins were seen to arise from the pelvic tumour with blood flow into the mesentery. The tumour was resected successfully and a histological diagnosis of leiomyoma was made. The blood ammonia concentration decreased to the normal range postoperatively. A follow-up portal venogram demonstrated decreased portal vein dilatation and minor portal-hepatic venous shunts, considered to be congenital in origin. It is concluded that hepatic encephalopathy was produced in this patient due to an excess portal blood flow from the huge pelvic leiomyoma via the mesentery, with portosystemic shunting through pre-existent (probably congenital) intrahepatic anastomoses.

Aged↗
PubMed1998

Evaluation of fasting serum insulin levels among Japanese school-age children.

We examined the physical constitution, serum lipids, fasting serum insulin (IRI), food intake, and physical activity in 1,330 children in three age groups (6-7, 9-10, and 12-13) in Nagao village for the period 1994-1996. Serum total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) levels were positively correlated, and HDL-C and TG were negatively correlated in all age groups. IRI was significantly higher among the elder children, and it was also higher in girls than in boys. IRI was positively correlated with the body mass index (BMI) and triceps skinfold thickness in ages 9-10 and 12-13, but no significant correlation was noted with waist/hip ratio (W/H ratio). In ages 12-13, IRI was positively correlated with TC and TG and negatively correlated with HDL-C. In high-IRI children (above 11.4 microU/mL) ages 12-13, the high-fat diet (fat-energy ratio above 30%) and low physical activity children (physical activity score below 10 points) were more frequent, and the mean levels of triceps skinfold were higher. The positive correlation between TC and HDL-C was not significant among high-IRI children. We concluded that a high-fat diet, low physical activity, and body fat accumulation influence the IRI level, which is closely related to serum lipid levels.

Adolescent↗
PubMed1998

Nine patients with hepatocellular carcinoma surviving for more than six years after treatment, including two patients who have survived without recurrence after hepatic lobectomy.

Of patients treated for hepatocellular carcinoma (HCC) accompanied by liver cirrhosis at our University Hospital between 1985 and 1990, clinical background factors in nine patients (7.0% of all patients) who survived for more than six years were examined to clarify the conditions that facilitate long-term survival. In particular, we describe two cases among these patients who have survived without the recurrence of a liver tumor for more than six years after hepatic lobectomy. In eight of nine patients, surgery was performed as the initial treatment. In seven patients, HCC was solitary and there was no portal invasion. Six patients were evaluated as Stage I according to clinical staging. Furthermore, the two patients without recurrence after treatment have been taking immunostimulators since their initial treatment until the present. The above observations suggest that surgical treatment should be considered in patients in whom hepatic reserve capacity is well maintained despite a tumor size greater than 2 cm. Subsequent recurrence should be detected earlier, and percutaneous ethanol injection therapy (PEIT) with a focus on maintaining liver function should be repeated. In addition, multi-disciplinary treatment including medication with immunostimulators is beneficial.

Aged↗
PubMed1997

Dual expression of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase in fibrotic human livers.

We have previously reported increased expression of matrix metalloproteinase-2 (MMP-2) using a rat model of liver fibrosis. However we did not clarify how the precursor of MMP-2 (proMMP-2) was activated. Therefore, we used human liver specimens with chronic hepatitis (CH) and liver cirrhosis (LC) to examine expression of membrane-type-1-MMP (MT1-MMP), which has recently been determined to activate proMMP-2. Northern hybridization studies showed a 5.4- and 1.4-fold increase in MMP-2 expression in CH and LC, respectively, as compared with normal liver. MT1-MMP gene expression simultaneously increased 4.0- and 1.4-fold in CH and LC, respectively. In situ hybridization using 35S-cRNA probes of MMP-2 and MT1-MMP showed prominent silver granules in elongated cells found in the lobules, periportal areas, and fibrous septa of CH and LC samples. These elongated cells expressed alpha-smooth muscle actin by immunohistochemistry. Immunoelectron microscopic examination localized MMP-2 and MT1-MMP to the rough endoplasmic reticulum of stellate cells located in the lobules and periportal areas, or to fibroblasts in the fibrous septa, suggesting that MMP-2 and MT1-MMP were produced by these cells. In addition, cytoplasmic and membranous immunodeposits of both MMPs were found in endothelial cells, Kupffer cells, capillary endothelial cells, and lymphocytes, indicating that activation of proMMP-2 occurs locally. Increased expression of MMP-2 and MT1-MMP was detected in CH and LC, while dual over-expression was found in stellate cells and fibroblasts, possibly resulting in the increase of active MMP-2 in and around these cells. These findings suggest that activated MMP-2 may remodel liver parenchyma during the process of liver fibrosis.

Adult↗
PubMed1997

Analysis of T-cell receptor Vbeta repertoire in liver-infiltrating lymphocytes in chronic hepatitis C.

BACKGROUND/AIMS: To examine the T-cell repertoire which is involved in the immunopathogenesis of chronic hepatitis, we analyzed the T-cell receptor Vbeta gene usage in liver-infiltrating lymphocytes by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical technique. METHODS: Complementary DNA was synthesized from RNA which was extracted from 26 liver biopsy specimens and from peripheral blood lymphocytes from eight subjects, and amplified by RT-PCR. Radioactivity of each amplified product using 32P-labeled primers was measured and the percentage of each Vbeta expression was calculated. RESULTS: The mean frequency of Vbeta5.1 (11.1%) in liver-infiltrating lymphocytes of chronic hepatitis C was highest among those of all Vbeta regions, and was significantly higher than that in both peripheral blood lymphocytes of chronic hepatitis C and liver-infiltrating lymphocytes of chronic hepatitis B. In the immunohistochemical analysis, Vbeta5.1-positive cells were mostly observed in portal areas where inflammatory reactions occurred. The sequences of the complementarity determining region (CDR)3 on T-cell receptor expressing Vbeta5.1 were examined in six patients with chronic hepatitis C. The sequences were similar to each other and all had one common amino acid (valine) irrespective of different HLA haplotype. CONCLUSIONS: These data suggest that Vbeta5.1-positive cells are preferentially accumulated in the liver of chronic hepatitis C and are involved in the immunopathogenesis of the disease. Sequence analysis showed that Vbeta5.1-positive cells recognize a common conventional antigen and valine recognized at the same position of the CDR3 may be a key residue in determining an antigen/major histocompatibility complex contact point.

Adult↗
PubMed1994

Reproducibility of major diagnoses in a binational study of lung cancer in uranium miners and atomic bomb survivors.

A binational panel of four Japanese and four American pathologists examined 208 pulmonary neoplasms, according to the World Health Organization (WHO) recommendations, second edition, for the histologic typing of lung tumors. The study design included independent evaluations by pathologists working alone, followed by group reviews. The individual evaluations, and their implications for reproducibility of the WHO recommendations, are reported. Consensus (agreement by six or more pathologists) with respect to major (ie, first digit) diagnosis was obtained for 76.4% of the cases. Consensus was obtained for 72.5% of the cases with any major diagnosis of small cell cancer; the comparable figures for adenocarcinoma and squamous cell carcinoma were 56% and 48%, respectively. American pathologists were twice as likely as Japanese pathologists to diagnose large-cell cancer, the only significant national difference. Consensus was far less frequent with the minor (ie, second digit) diagnosis categories. This study shows that lung cancers continue to be difficult to classify reproducibly.

Carcinoma↗
PubMed1993

Radiation-associated lung cancer: a comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki.

A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference.

Adenocarcinoma↗
PubMed1992

Evaluation of transcatheter arterial embolization with epirubicin-lipiodol emulsion for hepatocellular carcinoma.

A total of 18 patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) with a 4'-epi-doxorubicin (EDX)-lipiodol emulsion. Infusion of the EDX-lipiodol emulsion (EDX-L) via the hepatic artery was followed by the injection of gelatin sponge in 12 cases. The response and survival of these 12 patients following EDX-L treatment were compared with those of 42 subjects treated with a doxorubicin-lipiodol emulsion (DX-L) and those of 23 patients treated by TAE with gelatin sponge (GS) only. In the group treated with EDX-L, nine cases were AFP-positive in sera and four showed a decrease in serum AFP values to less than 10% of the pretreatment level. Seven cases showed a partial response, and nine cases showed no change in the size of the tumor. In the group treated with EDX-L, nine cases are alive, and the oldest has survived for more than 431 days since the treatment. The half-year survival value was 57%, and the 1-year survival value was 49%. These values did not differ significantly from those calculated for the group treated with DX-L. The 1-year survival value determined for patients treated with a lipiodol emulsion (EDX-L or DX-L) followed by GS was 65%, and the 2-year survival value was 39%. These results rates are significantly better than those obtained in patients treated with GS only (1-year survival, 39%; 2-year survival, 13%.

Aged↗