[Accumulation and transportation of methylmercury through the food chain reproduced in the model stream and its comparison to direct uptake from the water (author's transl)].
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Biomedical subjects
Publications and source records attributed to S Nambu.
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For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad-spectrum effectors, allogeneic cultured hepatoma cell lines (JHH-4 and HuH-6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour- and lymphokine-activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin-2 (rIL-2). The tumour-killing activity of ATLAK induced by HuH-6 was confirmed against HuH-6 and other different HCC cell lines (JHH-2, HuH-7 and PLC). These activated lymphocytes were significantly more potent than lymphokine-activated killer cells (LAK) in [51Cr]-releasing assay. The JHH-4 stimulated ATLAK was reactive not only with JHH-4 but also with JHH-2. The lysis of allogeneic targets could be partially inhibited by anti-CD8 and anti-CD3 but not by anti-CD4. Anti-tumour cytotoxicity in these cultures might be mediated by CD3+CD56- and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.
Thirteen of 81 patients with chronic hepatitis and positive hepatitis C virus (HCV) antibody developed hepatocellular carcinoma (HCC) during a follow-up period of 54 +/- 38 months. The histopathological findings in HCC-bearing liver in these patients included six cases of chronic persistent hepatitis [CPH; mean hepatitis activity index (HAI) score: 5.8] and seven cases of chronic aggressive hepatitis (CAH) 2A, or 2B (HAI) score: 13.6). Multiple biopsies of the liver in six cases revealed that five cases, including four with CPH at the time of HCC diagnosis, previously had histopathological findings identical to CAH 2A, and another case constantly had CPH during the 8-year follow-up. These findings suggest that HCV-associated HCC can occur even in patients with HCV antibody positivity and inactive or mild chronic hepatitis. This is of interest in the pathogenetic mechanisms of HCV-associated HCC.
Psychotropic action of a branched-chain-enriched amino acid solution (Aminoleban) was quantitatively and visually examined in six cirrhotic patients with mild hepatic encephalopathy (grades I and II) using electrophysiological and psychometric methods. Neurophysiological effects of the amino acid solution were observed by comparing topographic spectrum analyses of electroencephalography (EEG) before and immediately after an intravenous 3 h infusion of the solution. The delta wave in the frontal region diminished from 61 +/- 13 to 12 +/- 4% (P < 0.01) and the alpha wave in the occipital region increased from 11 +/- 3 to 51 +/- 11% (P < 0.01). Latencies of the P3 wave in visual evoked potentials, which were topographically recorded in the occipital region, shortened from 220 +/- 32 to 148 +/- 19 ms (P < 0.01). Latencies of the P300 wave in event-related potentials, which were topographically recorded in the centro-temporal region, shortened from 493 +/- 81 to 360 +/- 93 ms (P < 0.05). Topographic reaction pattern of P300 was irregular toward the occipital or parietal region in cirrhotic patients. The EEG frequency power spectrum, illustrated by the colour density spectral array of computer-aided polysomnography analysis, clearly showed a gradual increase of the alpha wave spectrum and a gradual decrease of the delta wave spectrum after initiation of the infusion. These immediate neurophysiological changes were confirmed by improvement of quantitative psychometric tests including number connection test, reaction time to sound, and digit symbol and block design tests of Wechsler Adult Intelligence Scale.(ABSTRACT TRUNCATED AT 250 WORDS)
Proliferating tumour cells in 92 patients with hepatocellular carcinoma (HCC) were identified by an immunohistochemical method using a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The rate of PCNA-positive cells in HCC tissues was positively correlated with histological grade and the tumour size and T factor of the tumour. In order to analyse the relationship between prognostic factors and cumulative survival rate after obtaining tumour specimens, 49 patients whose clinical courses could be followed after needle biopsy were selected for evaluation. These patients were treated by medical therapy alone. Analyses of prognostic factors by Cox's proportional hazard model revealed that the patient's prognosis was significantly correlated with PCNA-positive rates as well as the tumour size and mode of therapy. Moreover, the cumulative survival rates were significantly (P < 0.001) higher in patients with rates of PCNA-positive cells < 15% than in those with > or = 15%, even when tumour sizes were under 50 mm or tumours demonstrated the same degree of histological differentiation. These findings indicate that the PCNA-positive rate in biopsied tissues provides useful prognostic information in patients with HCC treated only by medical therapy.
The tumour cells of a human cholangiocarcinoma cell line, HuCC-T1, were found to express mRNA of interleukin-6 (IL-6) and to secrete a large amount of biologically active IL-6 in the culture medium at the concentration of 22.6 ng/mL. Interleukin-6 was demonstrated in the cytoplasm of the cells by immunohistochemical staining. Furthermore, these cells showed the presence of receptors for IL-6 on the surface, and DNA synthesis of the cells was stimulated by the exogenous addition of recombinant human IL-6 into the culture medium. The cell growth was significantly inhibited in the presence of anti-human IL-6 antibody in the culture medium. These findings indicate that IL-6 is one of the autocrine growth factors of this cell line in vitro.
Hypertensive diabetic patients are particularly prone to renal function impairment. A total of nine out-patients with diabetes and hypertension were, therefore, entered into this single-blind uncontrolled study on the effects of 50 mg/day atenolol on reducing blood pressure and preserving normal kidney functioning. Treatment and evaluations were continued for 12 months. Serum beta 2-microglobulin concentration was used as the index for measuring renal impairment. Atenolol significantly reduced heart rate, systolic and diastolic blood pressure, and serum beta 2-microglobulin concentrations compared with baseline. Plasma glucose and glycosylated haemoglobin levels were unchanged, and blood urea nitrogen levels were increased slightly (non-significant). Serum creatinine showed a tendency (non-significant) to reflect the changes in beta 2-microglobulin concentration. Ways in which atenolol may act to improve kidney functioning are suggested. It is concluded that atenolol is a favourable choice for the treatment of hypertension in diabetic patients with normally functioning kidneys since, even in long-term use, normal renal functioning is preserved.