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Patients with chronic hepatitis C frequently have serum and hepatic iron overload, but the mechanism is unknown. Recently identified hepcidin, exclusively synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. This study was conducted to determine the hepatic hepcidin expression levels in patients with various liver diseases. We investigated hepcidin mRNA levels of liver samples by real-time detection-polymerase chain reaction; 56 were hepatitis C virus (HCV) positive, 34 were hepatitis B virus (HBV) positive, and 42 were negative for HCV and HBV (3 cases of auto-immune hepatitis, 7 alcoholic liver disease, 13 primary biliary cirrhosis, 9 nonalcoholic fatty liver disease, and 10 normal liver). We analyzed the relation of hepcidin to clinical, hematological, histological, and etiological findings. Hepcidin expression levels were strongly correlated with serum ferritin (P < 0.0001) and the degree of iron deposit in liver tissues (P < 0.0001). Hepcidin was also correlated with hematological parameters (vs. hemoglobin, P = 0.0073; vs. serum iron, P = 0.0012; vs. transferrin saturation, P < 0.0001) and transaminase levels (P = 0.0013). The hepcidin-to-ferritin ratio was significantly lower in HCV(+) patients than in HBV(+) patients (P = 0.0129) or control subjects (P = 0.0080). In conclusion, hepcidin expression levels in chronic liver diseases were strongly correlated with either the serum ferritin concentration or degree of iron deposits in the liver. When adjusted by either serum ferritin values or hepatic iron scores, hepcidin indices were significantly lower in HCV(+) patients than in HBV(+) patients, suggesting that hepcidin may play a pivotal role in the pathogenesis of iron overload in patients with chronic hepatitis C.

Background and aim Low-grade fasting hyperbilirubinemia is a common observation in healthy subjects (HS), whereas high-grade fasting hyperbilirubinemia is believed to be a characteristic finding of Gilbert's syndrome. This study was undertaken to assess the role of mutation in bilirubin UDP- glycosyltransferase gene (UGT1A1) on fasting hyperbilirubinemia. Methods Analysis of UGT1A1 and a caloric restriction test (400 kcal for 24 h) were performed in 56 healthy subjects (25 males, 31 females), and 28 patients with Gilbert's syndrome (18 males, 10 females). There were 29 healthy subjects with no mutation in UGT1A1, and 27 healthy subjects and 26 Gilbert's syndrome patients with mutations in the coding and/or promoter (TATA box) regions of UGT1A1. Results The mean increment of serum bilirubin (DeltaSB) was 7.6 micromol/L [corrected] (males) and 4.1 micromol/L (females) in subjects with no UGT1A1 mutation. Subjects with mutation in UGT1A1 showed higher levels of DeltaSB than individuals without mutation. Among healthy subjects, gender difference in DeltaSB values was observed only in individuals with the wild type of UGT1A1, but not in those with mutations in this gene. Conclusion The results of the present study suggest that UGT1A1 mutation has a role in the development of high-grade fasting hyperbilirubinemia after caloric restriction.

In continuous billet casting, keeping the mold level steady is one of the most important technologies for maintaining steel quality. Using conventional methods, it is difficult to attain precise control of the mold level because of the nonlinear characteristics of the process. We have developed a control system using a neural network model to overcome this problem. In this paper, control problems of a continuous caster are introduced first. Next, the structure of the control system is proposed. In our proposed system, the neural network model recognizes the temporal patterns of inlet flow and controls the stopper stroke for a main control loop with a PI controller. The problems involved in construction of a valid neural network model that has good generalization and robust properties, are discussed from the viewpoint of optimizing the number of hidden layer units by the information criterion. Finally some results of its application are described.

The branched‐chain amino acid (BCAA)/tyrosine (Tyr) ratio (BTR) recently has been reported to be a good indicator of the severity of hepatic parenchymal injury in patients with chronic liver disease. In the present study, sequential changes of BTR after BCAA administration were determined in patients with chronic liver disease to evaluate the value of BTR as a marker of the clinical response to nutritional therapy in these patients. This study comprised 75 patients with chronic hepatitis and 96 with liver cirrhosis. BTR was significantly decreased in patients with cirrhosis and hepatitis compared with healthy subjects. BTR was significantly correlated with the Child‐Pugh score and with other liver function tests. BCAA increased significantly 2 hr after BCAA administration and decreased gradually thereafter. Tyr significantly decreased 4 hr after BCAA administration. BTR significantly increased 2 and 4 hr after BCAA therapy. The increase in BTR 3 hr after BCAA administration was low in patients with decreased basal BTR. The results of this study showed that BTR is a good index of the hepatic parenchymal damage and that it may be a useful marker for monitoring response to nutritional therapy in patients with chronic liver disease. J. Clin. Lab. Anal. 13:31–34, 1999. © 1999 Wiley‐Liss, Inc.

The magnetisation transfer ratio (MTR), a quantitative tissue characteristic, and the pallidal index were measured in the globus pallidus of 37 patients with hepatic cirrhosis and 37 control subjects. The MTR decreased with severity of the disease, as indicated by the serum total bililubin, indocyanine green 15-min retention rate, and plasma ammonia. The pallidal index correlated significantly with haematological parameters, although the correlation coefficients tended to be lower than those between MTR and haematological parameters. This change in MTR corresponded to the results of the manganese chloride experiments. T1 shortening in the pallidum of patients with cirrhosis is presumably caused by paramagnetic effects, and possibly attributed to manganese deposition.

The effect of 6 h transportation on plasma levels of catecholamines, cortisol, glucose and the number of eosinophils before, during and after the transportation was studied in adult male Japanese native Tokara goats. Blood was obtained via indwelling catheters in the jugular and femoral veins. During transportation, various behaviors apparently indicated nervousness or excitement. Plasma epinephrine levels increased immediately after the start, from a base value of 7.5 pmol ml −1 to 25.9 pmol ml −1 ( P −1 before transport and rose immediately after the start to a peak value of 166 ng ml −1 ( P −1 before the start to 165 mg dl −1 ( P −1 ( P

合鴨農法における家鴨類の適性品種を選定するため,マガモ,チェリバレーおよびF1(マガモ×チェリバレー)の3品種の行動および除草•防虫能力について比較検討した。試験田を3つの放飼区(マガモ,チェリバレーおよびF1)に分け,田植え1週間後にそれぞれ3品種の0日齢の雛を放飼し,放飼期間は稲の出穂期までの11週齢とした。結果を要約すると以下のとおりである。1. 水田内における労働時間(摂食行動と移動時間の合計)は,マガモが最も長く,次いでチェリバレー,F1の順であった。2. 水田内における休息時間は,F1,チェリバレーおよびマガモの順に長い傾向を示した。3. 1時間当たりの摂食行動回数は,マガモがF1およびチェリバレーに比較して多い傾向を示した。4. 水田内の発生状況調査から見た家鴨類の除草および防虫能力には,3品種間に有意な差は認められなかった。

The noninvasive determination of effective hepatic blood flow, intrahepatic shunted blood flow, intrahepatic shunt index, and total hepatic blood flow was investigated by using the sequential single photon emission computed tomography. This method was performed for a period of 10 minutes following an intravenous injection of 99mTc-(Sn)-N-pyridoxyl-5-methyltryptophan and a venous blood sampling. This study comprised 8 healthy volunteers, 16 patients with chronic hepatitis, and 33 patients with liver cirrhosis. The intrahepatic shunt index measured with this method coincided with the intrahepatic shunt index determined by catheterization, indicating the high reliability of this procedure. The effective hepatic blood flow in patients with liver cirrhosis was significantly lower than that in the healthy controls and the chronic hepatitis group. The intrahepatic shunted blood flow was significantly higher in patients with liver cirrhosis compared with the flow in healthy controls. The intrahepatic shunt index was also significantly higher in patients with liver cirrhosis compared with the index of healthy controls and those with chronic hepatitis. No substantial differences were noted in the total hepatic blood flow among the three groups. The effective hepatic blood flow, the intrahepatic shunted blood flow, and the intrahepatic shunt index, correlated with the serum albumin concentration, the serum cholinesterase level, and the plasma indocyanine green attenuation rate. From these results, it was concluded that the present procedure constitutes a reliable and effective method for the noninvasive determination of hepatic blood flows. Consequently, it will be of high clinical value for assessing the functional and the pathological alterations of the liver.

輸送開始時のストレッサーに対する反応に知覚-心理的経路が関与する可能性を明らかにするため,頸静脈と股静脈に残置カテーテルを装着した雄トカラヤギ3頭を用いて,ブランコ実験と実際の路上輸送試験を行なった.ブランコ実験ではケージにいれたままの自然の振動を組み合せた1セット15分間の振動を6回繰り返した.実際の輸送試験ではケージに入れたヤギをトラックに乗せて公道を3時間走った.ブランコ振動の間ヤギはあわててくずれた姿勢を直そうとし,また落ち着きのない行動を示した.ブランコ振動が始まるとすぐに,不規則で激しい振動のときヤギは急性で一過性の心拍数増加を示した.これと対照的に呼吸数はブランコ振動と関係がみられず,実際の経過時間と関係していた.ブランコ実験開始後30分には,血漿中のコルチゾールとグルコースがそれぞれ基礎値の4倍と3倍に上がっていた.プランコ運動終了時にはコルチゾールは同じく4倍に上昇した.そして,これらはプランコ終了後3時間で基礎値にもどった.ブランコによって好酸球は明らかに減少し開始後4.5時間で最小値を示した.白血球数は振動開始後漸増し,振動終了後3時間と12時間にピークを示した.トラック輸送では反応の大きさと持続時間がより明らかであったが,コルチゾールとグルコースは本質的にブランコ実験と同じ反応を示した.好酸球の減少は2頭にみられた.白血球数は輸送開始時から増加し,2時間後にピークを示した.コルチゾール,グルコースおよび白血球数の増加と好酸球数の減少のタイミングは,緊密に同期して実験開始直後から起っており,また,これらの反応はプランコ実験と実際の輸送試験の両方に認められた.今回の試験開始時における,実験動物の行動,コルチゾール,血液学的反応は,知覚-心理的経路の関与によって,動物が未知の処置と環境に対する恐怖と不安のために,驚愕反応を起しているにとを示唆している.

塩味(塩化ナトリウム),酸味(酢酸),甘味(ショ糖),苦味(カフェイン),旨味(グルタミン酸ナトリウム)およびアルコール(エタノール)に対する牛の味覚反応を2瓶選択法で調べた.これらの味物質を水道水に溶かしてそれぞれ7段階の濃度を設定し,低濃度から高濃度へ向けて実験を行なった.各濃度における総飲水量に対する試験液の摂取割合を選好指数とし,濃度上昇に伴う選好指数の推移を味覚反応曲線として表し,味覚反応を推察した.χ2-検定により,選好指数39.7%以上から60.3%未満は不弁別範囲,60.3%以上は選好範囲,39.7%未満は拒絶範囲と定義した.塩味物質は濃度1.25%で弱い拒絶反応を示した以外はほとんど水と弁別されなかった.牛は酸味物質に対して全体的に拒絶反応を示し,特に濃度0.08%以上では強い拒絶反応を示した.甘味物質は濃度0.16%から1.25%まではほとんど水と弁別されなかったが,2.5%以上では嗜好を示し,5.0%で最も強い嗜好を示した.苦味物質は濃度0.01%で弱い嗜好を示した以外はほとんど水と弁別されなかった.旨味物質は濃度0.08%以上では嗜好を示し,濃度0.63%で最も強い嗜好を示した.牛はアルコール物質に対して濃度1.6%で弱い嗜好を示した以外はほとんど水と弁別せず,濃度の上昇ににつれて強い拒絶反応を示した.

The antiviral effect of natural interferon (IFN)-α on chronic hepatitis C virus (HCV) infection was estimated by determining quantitative changes in serum HCV-RNA compared with the serum alanine aminotransferase (sALT) improvement; the relationships of responses to IFN according to the dose and period of IFN therapy were defined to determine an appropriate IFN therapy protocol. Twenty-two patients with chronic hepatitis C were given natural IFN-α and in 16 (72.7%) patients the viraemia was suppressed during therapy. Five (27.7%) of them sustained the disappearance of HCV-RNA for more than 6 months after therapy accompanied with a prolonged sALT improve-ment. Pre-treatment viraemia levels in 5 complete responders with "complete suppression" of viraemia were significantly lower than in 11 patients with a transient loss or a decline of HCV-RNA. Afavorable antiviral response was closely associated with a high total dose of IFN-α and a long duration of IFN therapy.(Internal Medicine 32: 523-529, 1993)

塩味(塩化ナトリウム),酸味(酢酸),甘味(ブドウ糖),苦味(塩酸キニーネ),旨味(グルタミン酸ナトリウム)に対する鶏•鶉の味覚反応を2瓶選択法で調べた.これらの味物質を水道水に溶かしてそれぞれ11段階の濃度を設定し,低濃度から高濃度へ向けて実験を行なった.各濃度における総飲水量に対する試験液の摂取割合を選好指数とし,濃度上昇に伴う選好指数の推移を味覚反応曲線として表し,味覚反応を推察した.X2-検定により,選好指数39.7%から60.3%は不弁別範囲,60.3%以上は嗜好範囲,39.7%以下は拒絶範囲と定義した.塩味の濃度は鶏が0.64%,鶉が1.28%まで弁別せず,鶏が1.28%,鶉が2.5%以上で拒絶反応を示した.酸味の濃度は鶏が0.04%,鶉が0.16%まで弁別せず,鶏が0.08%,鶉が0.32%以上で拒絶反応を示した.甘味の濃度は鶏が20%まで弁別せず,鶉は1.28%と2.5%で弱い嗜好を示した.苦味の濃度は鶏が0.02%まで弁別せず0.04%以上で拒絶反応を示し,鶉は0.32%まで弁別しなかった.旨味の濃度は鶏が0.64%,鶉が5%まで弁別せず,鶏が1.28%以上,鶉が10%で拒絶反応を示した,以上の結果より,鶏と鶉は特に強い嗜好を示す味物質はないことと,鶏は鶉より味覚が敏感であることが明らかとなった.

特発性急性妊娠脂肪肝(Idiopathic acute fatty liver of pregnancy, IAFLP)の1救命例を経験し,その経時的な肝容積の変化と肝組織所見とを比較検討したので報告する.症例は36歳3回経妊3回経産婦.妊娠38週より黄疸,意識障害が出現.男児を分娩後,当科に緊急入院となった.CTスキャンによる肝容積は第2病日に約703cm3と減少を認めたが,肝機能の改善とともに第8病日には約1,390cm3と急速に正常化した.第12病日の肝組織所見では,肝細胞の壊死・脱落は軽微であり,肝容積の変化はおもに,個々の肝細胞の萎縮から腫大への変化に起因するものと考えられた.IAFLPの経過予後の判定に肝CTスキャンによる経時的な肝容積の測定は有用であった.

Many patients with porphyria cutanea tarda (PCT) have been reported to be hepatitis C virus (HCV) carriers, suggesting that HCV infection plays a role in the pathogenesis of this type of porphyria. In this study, we report a patient with chronic hepatitis C-associated PCT. Therapy with interferon (IFN) transiently decreased HCV RNA levels, but levels of urinary porphyrins and serum transaminases and ferritin remained unchanged. Serum ferritin and urinary porphyrin levels improved after phlebotomy, but this therapy was not effective in improving serum transaminase levels. Although a physiopathological association between HCV infection and PCT has been suggested previously, IFN was not effective in this patient. The transient decrease in HCV RNA levels was a factor independent of porphyrin metabolism.

The clinical and histologic changes in 116 Japanese patients with persistent HBs-antigenemia and chronic liver diseases were analyzed after the patients were divided into three groups depending on the history of alcohol consumption. Group 1 consisted of 45 nondrinkers, Group 2 of 51 social drinkers, and Group 3 of 20 habitual drinkers with a daily intake of more than 60 g of ethanol for at least ten years. The frequency of chronic active hepatitis (CAH) in Group 3 was higher than in Groups 1 and 2 (P less than 0.05). The histologic comparison of patients with CAH between the three groups revealed that only the inflammatory changes at/near portal tracts, such as piecemeal necrosis and inflammatory cell infiltration in Group 3, were more prominent than those in Groups 1 and 2. The alcohol-related changes except for fatty change were not found in any specimens. These findings suggest that alcohol intake, particularly of more than 60 g of ethanol a day, may enhance the viral inflammatory changes of the liver in patients with persistent HBs-antigenemia.

Although bacteremia caused by non-typhoidal salmonella is frequently observed in immunocompromised hosts, it is rare to find this condition in healthy subjects. In this report, we present a case of bacteremia due to Salmonella enteritidis detected in a healthy man. A 59-year-old man was admitted to our hospital with a fifty-day history of fever on May 18, 1985. On admission, he showed no symptoms except high body temperature (38.8 degrees C). In the laboratory data, C-reactive protein was 3+, white- cell count was 9600, and erythrocyte sedimentation rate was 12 mm/h. Culture in blood and stool yielded Salmonella enteritidis. However, no abnormal findings were found in UGIS, barium enema, OC + DIC, abdominal CT and echography. As soon as Ampicillin was administered, the fever was gone and the blood culture yielded nothing. After six months, the stool culture was negative for pathological intestinal bacterial flora and he was in good physical condition. Generally, bacteremia develops mainly in the immunocompromised hosts, such as patients with neoplastic disease, AIDS, leukemia or collagen disease. The literature provides so far twenty three adult cases of bacteremia due to non-typhoidal salmonella in Japan. Only two of them had no systemic disease as well as our case. Although it is unknown why bacteremia developed in this healthy man, we reported that bacteremia developed rarely in subjects with healthy condition.

Background: Oxidative stress plays an important role in the pathogenesis of chronic liver diseases. The plasma level of 8-isoprostane, a product of lipid peroxidation, is a marker of oxidative stress in vivo. The aim of the present study was to clarify whether the degree of lipid peroxidation, as measured by the plasma level of 8-isoprostane, influences the progression of chronic liver diseases and hepatocarcinogenesis. Methods: Plasma 8-isoprostane levels were investigated in 14 patients with non-alcoholic fatty liver disease (NAFLD), 75 with chronic hepatitis C (CH-C), 14 with cured CH-C, 14 with HCV-positive hepatocellular carcinoma (HCC-C) and 38 healthy volunteers. 8-Isoprostane was measured by enzyme immunoassay after affinity column purification. Results: Plasma 8-isoprostatne was significantly elevated in NAFLD (11.9 [3.8–56.8] pg/mL), CH-C (10.1 [4.2–134.5] pg/mL) as compared to controls (6.3 [3.6–11.1] pg/mL). Plasma 8-isoprostane values were positively correlated with body mass index in NAFLD (P

An association of hepatitis C virus (HCV) with low-density lipoproteins (LDL) in serum of patients with chronic hepatitis C (CHC) has been suggested. We conducted a prospective study in CHC patients complicated with hyperlipidaemia, to examine whether bezafibrate, which is commonly used for treatment of hyperlipidaemia, reduces serum HCV-RNA titre and improves liver dysfunction. Fifteen patients received daily oral bezafibrate treatment (400 mg/day) for 8 weeks, and its effects on serum lipids, transaminases, HCV-RNA titres, and HCV-RNA titres bound to LDL were evaluated. Fifteen untreated patients with CHC and hyperlipidaemia were used as controls. The mean serum alanine aminotransferase levels and HCV-RNA titres significantly decreased at the end of bezafibrate therapy in the treated group (105 +/- 34 to 80 +/- 32 IU/L, P = 0.02 and 2.23 +/- 2.71 to 1.78 +/- 2.38 x 10(7) copies/mL, P < 0.01 respectively), but no changes were observed in the control group. Serum HCV-RNA titres bound to LDL, as quantified by immunoprecipitation using anti-LDL antibody, also decreased in all 15 treated patients [5.55 +/- 6.59 to 1.07 +/- 1.58 x 10(6) copies/ml, P < 0.01 (mean reduction rate was -78.5 +/- 17.0%)]. Sucrose density-gradient ultracentrifugation study revealed that HCV-RNA-decreased density fractions after the bezafibrate were identical to LDL-density fractions (1.015-1.062 g/mL). Eight CHC patients were treated with bezafibrate, interferon, and ribavirin triple therapy for 32 weeks, and four patients achieved sustained virological response to therapy. This pilot study provides further evidence of an association between HCV and LDL in serum and suggests the potential usefulness of bezafibrate as an anti-HCV reagent for the treatment of CHC patients.

Backgrounds: It has been reported that histological activity index and piecemeal necrosis are good factors to evaluate the prognosis in patients with chronic hepatitis C (CHC). Thus, there is a need for simple and noninvasive means to assess disease activity and piecemeal necrosis in patients with CHC. In this study, we measured the serum concentrations of large splice variants of tenascin-C (cTN-C) in patients with CHC, and examined their correlation with the degree of inflammatory activity and fibrosis as evaluated in liver biopsy specimens. Methods: The serum levels of cTN-C in 150 patients with CHC and 50 healthy volunteers were measured by enzyme-linked immunosorbent. The histology of liver biopsy specimens was also evaluated following the Desmet's grading/staging system and the Ishak's classification. Liver specimens obtained by biopsy were also immunohistochemically evaluated with anti-human tenascin-C antibodies. Results: Serum cTN-C concentrations were significantly higher in CHC patients than in healthy volunteers (P

Hepatitis C virus (HCV) has been reported to exist in the circulation of patients in various forms such as free virions, immune complexes, and nucleocapsids. To clarify the clinical significance of serum HCV titers according to the forms of virus particles, we evaluated the immune complexed (IC) and nonimmune complexed (NIC) HCV RNA titers in 77 chronic hepatitis patients treated with interferon (IFN).IC and NIC forms in pretreatment serum were separated by immunoprecipitation using antihuman immunoglobulin antibody, and quantified by reverse transcription polymerase chain reaction.Serum titers of NIC HCV RNA were correlated with those of whole serum HCV RNA (r = 0.96, p0.01) and IC HCV RNA (r = 0.98, p0.01), but they were not with the aminotransferase levels, gamma-globulin concentration, and grading or staging of liver histology. Nonresponders to IFN had significantly high NIC HCV RNA titers compared with sustained responders (10(4.93 +/- 0.81) copies/ml vs 10(4.06 +/- 0.69) copies/ml, p0.01). It is noteworthy that the relative amount of NIC HCV RNA to whole serum HCV RNA was also significantly higher in nonresponders than in sustained responders (0.66 +/- 0.10 vs 0.50 +/- 0.11, p0.0001). Multivariate analysis showed that low NIC HCV RNA titer (p0.01) and genotype 2 (p = 0.02) were independent variables contributing to sustained response to IFN, but the whole serum HCV RNA titer was not.Pretreatment NIC HCV RNA titer is a more reliable predictive marker than genotype or whole serum HCV RNA of a sustained response to IFN monotherapy. This finding suggests that humoral immunity may affect the response to IFN.

Objective Alterations of regional cerebral blood flow (rCBF) in subjects with liver cirrhosis have not been fully evaluated. We evaluated quantitative changes in rCBF using single photon emission computed tomography (SPECT). Methods Twenty-eight Japanese patients with liver cirrhosis were enrolled in this study. None of them exhibited advanced hepatic encephalopathy at the time of examination. The cause of liver cirrhosis was viral infection in 26 patients; the cause was unknown in two patients. Child-Pugh classification of the patients was as follows: Group A, 12 patients; Group B, 12 patients; and Group C, four patients. The control group consisted of 25 age-matched healthy subjects. Radionuclide angiography was performed by rapid injection of Tc-99m ethyl cysteinate dimer (ECD) (740 MBq) via the right cubital vein, and then SPECT brain images were taken. Using the Patlak graphical method, rCBF values (ml/100 g per min) were calculated in the frontal, parietal, temporal and occipital lobes and cerebellum on SPECT images. Results The rCBF values were lower in cirrhotic patients than in controls, i.e. by 15% in the frontal lobe, by 12% in the parietal lobe, by 10% in the temporal and occipital lobes, and by 7% in the cerebellum. They decreased concomitantly with the severity of liver disease. A significant negative correlation was noted between rCBF values and Child-Pugh score in the frontal (P < 0.01), parietal (P < 0.05) and occipital lobes (P < 0.01). rCBF values of each region were not correlated with age or with results of neuropsychological test. The degree of association between rCBF values and results of laboratory examination was generally poor. Conclusion Patients with liver cirrhosis without advanced encephalopathy showed widespread reduction in rCBF; this reduction was particularly evident in the frontal lobe. Tc-99m ECD SPECT may be useful for evaluating cerebral functional changes in patients with liver cirrhosis.

Background Many patients with hepatocellular carcinoma are positive for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C virus (anti-HCV). Recently, transfusion-transmitted virus (TTV) DNA was identified in the serum of patients with non-B, non-C posttransfusion hepatitis. In this study, the prevalence of TTV DNA in the serum of patients with non-B, non-C hepatitis-associated hepatocellular carcinoma was evaluated. Methods Fifteen patients with hepatocellular carcinoma negative for HBsAg, antibodies to hepatitis B core antigen (anti-HBc), and anti-HCV antibodies were enrolled in this study (non-B, non-C group). Fifteen patients positive for HBsAg and negative for anti-HCV antibody (HBV group) and another group of patients negative for HBsAg but positive for anti-HCV antibody (HCV group) were also enrolled in this study. Data obtained from 27 healthy subjects negative for both HBsAg and anti-HCV antibody and normal levels of serum alanine aminotransferase represented controls. The healthy control group, the non-B, non-C group, and the HCV group were age-matched. TTV DNA was detected by heminested polymerase chain reaction in which specific primers were used. Results TTV DNA was detected in 10 of 15 patients (67%) in the non-B, non-C group. This prevalence rate in the non-B, non-C group was significantly higher than that in the HBV group (3 of 15 patients, 20%) and the control group (9 of 27 patients, 33%), but it was not significantly different from that in the HCV group (7 of 15 patients, 47%). The noncancerous hepatic tissue samples of 10 TTV-DNA positive patients in the non-B, non-C group included 2 with chronic hepatitis and 8 with cirrhosis. Conclusions This study showed that TTV DNA is frequently detected in the serum of patients with non-B, non-C hepatocellular carcinoma. This result suggests a potential pathogenetic association between hepatocellular carcinoma and TTV infection.

We report a case of alanine aminotransferase (ALT) deficiency in a 68-year-old Japanese female with chronic hepatitis C. The serum was positive for antibody to hepatitis C virus (HCV) and HCV-RNA. Liver biopsy showed histological evidence of chronic active hepatitis. The level of serum aspartate aminotransferase (sAST) was elevated, but sALT was extremely low. The patient was followed up for her serum aminotransferase levels for 1.5 years under the treatment with ursodeoxycholic acid. The low sALT level persisted during all the follow-up period. The ALT activity in liver tissue was also decreased. Based on these findings, ALT deficiency was suspected. sALT activity was also found to be low in her two sons. This latter finding suggests the hereditary character of this abnormality.

By using commercially available ELISA kits, serum IL‐6 and TNF‐α levels in healthy adults, and the levels of various cytokines in patients with primary biliary cirrhosis or chronic viral liver diseases, were investigated. IL‐6 levels of healthy subjects were distributed in a wide range, and the distribution pattern was similar to those of the patients. TNF‐α levels tended to be low in females in their 30s, but there were no abnormalities in the patients. Characteristic findings, in the primary biliary cirrhosis patients, were an increase of IFN‐γ and IL‐2 levels, and a decrease of GM‐CSF levels (P

Prepuberal gilts were injected intramuscularly with human chorionic gonadotropin (HCG)(6 IU/kg of body weight) 72 hr after receiving pregnant mare serum gonadotropin (PMS) (12 IU/kg of body weight) and ovulation was verified by laparotomy. Changes in concentrations of prostaglandins (PGs) and steroids in peripheral plasma, ovarian vein plasma and follicular fluid were examined. Ovulation occurred 32 to 48 hr after HCG administration. Progesterone levels were low at the time of HCG administration, but markedly increased after ovulation. Estradiol-17β and testosterone levels which reached maximum values 72 hr after PMS administration, decreased after HCG administration and remained low until about 36 hr after ovulation. Levels of PGF2α in ovarian vein reached maximum values near the time of ovulation. Concentrations of PGE1, PGF2α and 6-keto-PGF1α in follicular fluid remained relatively low until 18 hr after HCG injection followed by an increase 36 to 42 hr after HCG administration and reached maximum values as expected time of ovulation approached. In gilts given indomethacin 24 hr after HCG injection, ovulation was inhibited in a dose-dependent manner. But patterns of steroid secretion in indomethacin-treated gilts were similar to those of controls. Levels of PGE1 and PGF2α in the follicular fluid were low 48 and 72 hr after HCG injection. These results suggest that PGs play an important role in process of ovulation in gilts as well as in other animals.