Toshiyuki Nakamura

Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma

Background. In patients with hepatocellular carcinoma (hepatoma), the rate of recurrent and second primary hepatomas is high despite surgical resection and percutaneous ethanol-injection therapy. We developed an acyclic retinoid, polyprenoic acid, that inhibits hepatocarcinogenesis in the laboratory and induces differentiation and apoptosis in cell lines derived from human hepatoma. In a randomized, controlled study, we tested whether the compound reduced the incidence of recurrent and second primary hepatomas after curative treatment. Methods. We prospectively studied 89 patients who were free of disease after surgical resection of a primary hepatoma or the percutaneous injection of ethanol. We randomly assigned the patients to receive either polyprenoic acid (600 mg daily) or placebo for 12 months. We studied the remnant liver by ultrasonography every three months after randomization. The primary end point of the study was the appearance of a histologically confirmed recurrent or new hepatoma. Results. Treatment with polyprenoic acid significantly reduced the incidence of recurrent or new hepatomas. After a median follow-up of 38 months, 12 patients in the polyprenoic acid group (27 percent) had recurrent or new hepatomas as compared with 22 patients in the placebo group (49 percent, P = 0.04). The most striking difference was in the groups that had second primary hepatomas-7 in the group receiving polyprenoic acid as compared with 20 in the placebo group (P=0.04 by the log-rank test). Cox proportional-hazards analysis demonstrated that as an independent factor, polyprenoic acid reduced the occurrence of second primary hepatomas (adjusted relative risk, 0.31 ; 95 percent confidence interval, 0.12 to 0.78). Conclusions. Oral polyprenoic acid prevents second primary hepatomas after surgical resection of the original tumor or the percutaneous injection of ethanol.

Electron microscopic study of the blood-brain barrier in rats with brain edema and encephalopathy due to acute hepatic failure

SummaryAn electron microscopy study was conducted to investigate structural as well as functional changes of the blood-brain barrier in hepatic encephalopathy. Hepatic encephalopathy was induced in rats by two-stage hepatic devascularization producing ischemic liver damage. The permeability of the blood-brain barrier to lanthanum, horseradish peroxidase and [3H]inulin was determined, with electron microscopy performed on capillaries from different regions of rat brain. Marked swelling of the perivascular astroglial foot process and dilatation of extracellular spaces were observed in the cerebral cortex, pons, basal ganglia and cerebellar cortex in rats with acute hepatic failure. Diffusion of lanthanum and reaction products of horseradish peroxidase were completely restricted by intercellular tight junctions, but there was a significant increase in the amount of [3H]inulin leaking out of the capillaries in the cerebral cortex in rats with acute hepatic failure as compared with controls. [3H]inulin was found mainly in vesicles, vacuoles and endoplasmic reticulum. Our results indicate that brain edema in acute hepatic encephalopathy is mainly of the cytotoxic type and, to a lesser extent, of the vasogenic type, due to the increase of vascular permeability via the vesicle system.

Synthesis of silicon carbide fibers by sol-gel processing

Silica-phenolic resin hybrid fibers with carbon-to-silicon atomic ratios of 2.6 to 5.4 have been prepared from ethanol solutions of tetraethoxysilane, phenolic resins, water, and hydrochloric acid with a tetraethoxysilane-H2O−HCl molar ratio of 1:2:0.01 by sol-gel processing. The hybrid fibers have been heated at 1500°C in Ar for carbothermal reduction to convert them into silicon carbide fibers. The effects of the holding time at 1500°C and the carbon-to-silicon atomic ratio of the hybrid fibers on the free carbon content in the silicon carbide fibers have been investigated. It has been found that the conversion is complete by the heat-treatment for more than 2 h. The silicon carbide fibers with a free carbon content of ca. 2 wt% have been obtained from the hybrid fibers with the ratios of 2.6 to 4.3.

Erectile dysfunction in patients with chronic viral liver disease: its relevance to protein malnutrition

BackgroundIn patients with chronic liver disease (CLD), quality of life is generally accepted as poor, especially for physical function. However, sufficient data regarding erectile function has not been shown in patients with CLD. The international index of erectile function (IIEF) is widely used to assess erectile function, and a short form of the IIEF was recently developed (IIEF-5). Using this questionnaire, we evaluated erectile dysfunction (ED) in patients with CLD.MethodsA total of 117 Japanese patients (64 with chronic hepatitis [CH] and 53 with liver cirrhosis [LC]) were analyzed. The etiologies were hepatitis B virus (HBV) in 21, HCV in 94, and non-B non-C in 2. The IIEF-5 and Medical Outcomes Study Short Form 36 (SF-36) were administered to the patients, and biochemical analyses for items serum albumin, prothrombin time, bilirubin, and ammonia were also performed.ResultsThe incidence of ED was 85% in the total cohort with CLD, 78% in those with CH, and 92% in those with LC (P < 0.05 between CH and LC). ED was found in 50% of CLD patients under age 50 years, in 79% aged 50–59, and in 100% aged over 60 (P, overall <0.001). The scores for ED severity correlated with increasing grades of a modified Child-Pugh classification (P < 0.05). Simple regression analysis showed age (P < 0.01), physical function (P < 0.001), role physical (P < 0.001), and social functioning (P < 0.05) on the SF-36, and serum albumin (P < 0.001) as significant determinants of ED. Multiple regression analysis identified age (P < 0.001) and serum albumin (P < 0.001) as independent significant factors that determined ED.ConclusionsThese data clearly demonstrate that liver disease is the cause of ED in patients with CLD, and serum protein status could be relevant to this condition in these patients.

Silica gel-phenolic resin hybrid fibres: new precursors for continuous β-silicon carbide fibres

Silica gel-phenolic resin hybrid fibres have been synthesized by hydrolysis and polycondensation of tetraethoxysilane [Si(OC2H5)4, TEOS] in the presence of phenolic resins in ethanol under acidic conditions. The fibres had C : Si atomic ratios of 2.6–5.4 and could be converted into β-silicon carbide (SiC) fibres by carbothermal reduction at 1500 °C under an argon atmosphere.

Esophageal metastasis from prostate cancer: Diagnostic use of reverse transcriptase-polymerase chain reaction for prostate-specific antigen

An extremely rare case of esophageal metastasis from prostate cancer is reported. A 65-year-old man presented with anorexia and back pain. Upper gastrointestinal X-ray fluoroscopy and endoscopy revealed a shallow longitudinal ulcer, with converging mucosal folds, approximately 5 cm above the esophagogastric junction. The histological diagnosis of the biopsied specimen was adenocarcinoma. Blood biochemistry revealed elevated serum prostatespecific antigen (PSA) and γ-seminoprotein levels. Ultrasonography of the prostate disclosed a hypoechoic lesion in the left lobe, and needle biopsy led to the diagnosis of prostatic adenocarcinoma. Since there was no finding suggestive of a primary lesion, apart from that in the prostate, we conducted reverse transcriptase-polymerase chain reaction (RT-PCR) for PSA. PSA-positive mRNA was demonstrated in the tissue of the esophageal tumor. There are three reports on metastasis to the esophagus from prostate cancer, but this is the first case of esophageal metastasis from prostate cancer without any evidence of metastasis to other organs. The importance of RT-PCR for the diagnosis of primary lesions of metastatic cancer is discussed.

Synthesis of continuous silicon carbide-titanium carbide hybrid fibers through sol-gel processing

Abstract Silica-titania-phenolic resin hybrid fibers have been prepared from ethanol solutions of tetraethoxysilane (TEOS), titanium tetrakis(2,4-pentanedionate) (TTP), and novolac-type phenolic resins, where water and HCl have been added at a (TEOS + TTP):water:HCl molar ratio of 1:2:0.01, by sol-gel processing. The Si-to-Ti atomic ratio of the hybrid fibers was varied down to 10.4 by changing the amounts of TEOS and TTP in the starting solutions. Carbothermal reduction of both silica and titania components of the hybrid fibers has taken place at 1500 °C in an Ar flow, resulting in the formation of continuous β-silicon carbide-titanium carbide hybrid fibers with Si-to-Ti atomic ratios varied down to 9.9.

Changes in brain monoamine metabolism in rats with acute ischemic hepatic failure under artificial cardiopulmonary management

SummaryA study was conducted to investigate changes in monoamine metabolism in the brain of rats with acute ischemic hepatic failure (AHF) induced by two-stage hepatic devascularization. Strict artificial cardiopulmonary management was used to exclude possible confounding effects of hypotension, hypothermia and hypoxemia that often appear in AHF. Rats were put in an incubator at 34°C before the ligation of the hepatic artery (second stage operation), tracheotomized and ventilated artificially throughout the remaining experimental periods. No significant difference was observed in physiological parameters, including body temperature, pulse rate and systolic arterial blood pressure or PaO2 between AHF and sham operated rats. Brain levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), and serotonin (5-hydroxytryptamine, 5HT) and its metabolite 5-hydroxyindoleacetic acid (5HIAA) were determined by HPLC-voltametry. AHF rats showed significantly higher MHPG, DOPAC, 5HIAA and lower NE levels in the brain compared to controls. In addition, a significant negative correlation between NE and tyrosine (Tyr), a significant positive correlation between MHPG and Tyr or phenylalanine (Phe), and a significant positive correlation between DOPAC and Tyr or Phe were observed. In conclusion, the changes in monoamine metabolism in the brain of AHF rats are clearly induced specifically by hepatic failure itself, possibly through an altered metabolism of amino acids.

メチシリン耐性黄色ブドウ球菌 (MRSA) の検出: 気道と消化管との関連性

The study was conducted to elucidate the possibility of hospital infection of methicillin-resistant Staphylococcus aureaus (MRSA) through feces. Fecal cultures of 12 inpatients positive for MRSA in the respiratory tract and 11 inpatients negative for MRSA in the respiratory tract were performed from April to October in 1993. Fecal cultures of inpatients positive for MRSA in the respiratory tract were continued until September in 1996, finally a total of 50 cases were enrolled. MRSA was isolated from feces of 7 patients (58.3%) of the 12 patients positive for MRSA in the respiratory tract, while no MRSA was isolated from feces of 11 patients negative for MRSA in the respiratory tract. Twenty-seven patients (54.0%) of 50 patients positive for MRSA in the respiratory tract yielded MRSA in the feces. Twenty-three patients (85.2%) of the 27 patients positive for MRSA in the fecal flora had received H2-blocker, while 11 patients (47.8%) of the 23 patients negative for MRSA in the fecal flora received H2-blocker; these differences were statistically significantly (p < 0.01). These findings suggest the possible role of feces in hospital infection with MRSA and the necessity for careful administration of H2-blocker to patients positive for MRSA in the respiratory tract.

Effects of benzodiazepine on neurotransmitter receptors in the brain of rats with acute ischemic hepatic failure: With special relations to the kinetics of .GAMMA.-aminobutyric acid binding.

肝不全時の脳内神経伝達物質レセプターに対するベンゾジアゼビン(BDZ)投与の影響をGABA結合能を指標として検討した.対照ラットより調製した脳シナプス膜では,BDZ10-12MでBDZ非添加時に比し14%と最大のGABA結合能の増強を示し,より高濃度ではむしろ増強効果の減弱を認めた.一方,肝不全ラットでは,10-12Mで7%, 10-11Mで32%とGABA結合能は濃度依存性に増強効果を示し,10-10～10-8Mで34%と平衡に達した.この結合能の増強はkinetic studyの結果,対照ラットでは低親和性結合部位のaffinityの増強,肝不全ラットでは同部位のaffinityのより強い増強とdensityの増加の両者によることが判明した.以上より肝不全時には,BDZ投与によりGABA結合能が対照群に比し,より増強すること,すなわち脳内神経伝達物質レセプターレベルでの異常が存在する可能性が強く示唆された.