Alcohol consumption appears to protect against non-alcoholic fatty liver disease.

BACKGROUND: Moderate alcohol consumption may have certain beneficial effects against non-alcoholic fatty liver disease, which is associated with metabolic syndrome. AIM: To determine the association between drinking pattern and fatty liver in Japanese men and women. METHODS: A cross-sectional study was performed with health checkup data including information concerning alcohol consumption and ultrasonographic assessment of fatty liver. RESULTS: We analysed 4957 men and 2155 women without reported liver diseases (median age, 49 years). In men, 40% of nondrinkers and 28% of drinkers had fatty liver. Alcohol consumption was inversely associated with fatty liver (adjusted odds ratio, 0.54; 95% confidence interval, 0.46-0.63). The prevalence of fatty liver in each category of drinking frequency was 38% (1-3 days/week), 29% (4-6 days/week), and 24% (daily drinking); there was a significant inverse correlation between drinking frequency and the prevalence of fatty liver (P < 0.001). In women, 16% of nondrinkers and 10% of drinkers had fatty liver. Drinking less than 20 g on 1-3 days/week was associated with low prevalence of fatty liver (adjusted odds ratio, 0.47; 95% confidence interval, 0.23-0.96). CONCLUSIONS: Alcohol consumption appears to protect against non-alcoholic fatty liver disease.

Genetic and epigenetic alterations of Ras signalling pathway in colorectal neoplasia: analysis based on tumour clinicopathological features.

Activation of RAS signalling induced by K-ras/BRAF mutations is a hallmark of colorectal tumours. In addition, Ras association domain families 1 and 2 (RASSF1 and RASSF2), the negative regulators of K-ras, are often inactivated by methylation of the promoter region in those tumours. However, reports showing differences in the occurrence of these alterations on the basis of tumour characteristics have been scarce. We analysed K-ras/BRAF mutations and the methylation status of RASSF1 and RASSF2 promoter regions in 120 colorectal adenomas with respect to their clinicopathological features. K-ras/BRAF mutations and RASSF2 methylation were observed in 49 (41%) and 30 (25%) of the samples, respectively, while RASSF1 methylation was observed in only 3 (2.5%). Adenomas with RASSF2 methylation often carried K-ras/BRAF mutations simultaneously (22 out of 30, P<0.01). Multivariate analysis revealed that the concomitance of these alterations was frequently observed in serrated adenomas (odds ratio (OR) 11.11; 95% confidence interval (CI) 1.96-63.00), but rarely in adenomas located in the sigmoid or descending colon (OR 0.13; 95% CI 0.03-0.58). A comparison between adenomas and cancers showed a significantly higher prevalence of these alterations in cancers than in adenomas in the proximal colon (58 vs 27%, P=0.02). Frequency and the time point of the occurrence of Ras signalling disorders differ according to colorectal neoplasia's characteristics, particularly the location.

Predictive factors of efficacy of leukocytapheresis for steroid-resistant ulcerative colitis patients.

BACKGROUND: The effectiveness of leukocytapheresis against ulcerative colitis has been reported. However, the efficacy of this therapy for steroid-resistant ulcerative colitis patients has hardly been examined. AIMS: The aims of this study are to evaluate the efficacy of leukocytapheresis for steroid-resistant ulcerative colitis patients and to identify clinical factors that predict the efficacy of this therapy for these patients. METHODS: Clinical factors of 71 steroid-resistant ulcerative colitis patients who underwent leukocytapheresis analysed. RESULTS: Of those analysed, 53 (75%) patients showed an initial response to leukocytapheresis. Among cases with initial response, however, only 19 (27%) patients maintained remission for more than 6 months. Steroid-dependent course (Odds ratio =5.53, 95% confidence interval; 1.24-24.73) and a high C-reactive protein degree (Odds ratio=1.6, confidence interval; 1.09-2.35) were predictors of initial response to leukocytapheresis. Rapid response, which means remission induction within three leukocytapheresis sessions, was the only predictor of maintenance of remission for more than 6 months after successful leukocytapheresis therapy (odds ratio=8.01, confidence interval; 1.08-59.37). CONCLUSIONS: Leukocytapheresis was effective for steroid-resistant ulcerative colitis patients. However, relapse was frequently observed within short periods after the initial response to this therapy. Patients without a rapid response should be treated with alternative or additional therapies.

Helicobacter pylori eradication reduced the incidence of gastric cancer, especially of the intestinal type.

BACKGROUND: Although Helicobacter pylori infection is closely associated with gastric cancer development, follow-up studies after H. pylori eradication are still scarce. AIM: To clarify the cancer preventive effect of H. pylori eradication, with special attention to differences in effect according to histology. METHODS: Patients who underwent H. pylori eradication therapy and were followed-up endoscopically for at least 1 year were analysed. The incidence of gastric cancer and factors associated with cancer development were investigated. RESULTS: A total of 1807 patients were enrolled. Six of 1519 H. pylori eradicated and five of 288 persistent subjects developed gastric cancer. Four of the eradicated subjects developed the intestinal type and two the diffuse type, while four of the persistent subjects developed the intestinal type and one the diffuse type. Kaplan-Meier analysis indicated a significantly lower incidence in eradicated patients than in persistent patients. The incidence of intestinal type was significantly lower than in eradicated patients, while the diffuse type could not be evaluated because of the low incidence. CONCLUSIONS: Helicobacter pylori-eradicated patients had a reduced incidence of gastric cancer compared with H. pylori-persistent patients, particularly the intestinal type, suggesting that H. pylori is strongly associated with intestinal-type gastric cancer.

Clinical characteristics of synchronous colorectal cancer are different according to tumour location.

AIMS: The purpose of this study was to investigate the clinical characteristics of synchronous cancer patients, with particular attention given to variations in tumour location. METHODS: A retrospective evaluation of 249 synchronous cancer cases out of 3061 consecutive colorectal cancer patients. RESULTS: Multivariate analysis of risk factors for synchronous cancer according to tumour location revealed that male gender was a significant risk for synchronous lesions in the left colon only (odds ratio=2.05, 95% confidence interval 1.34-3.13). Meanwhile, aging was a risk factor for synchronous cancer in the right colon only (odds ratio=1.05, 95% confidence interval 1.02-1.08), and in both sides of the colon (odds ratio=1.03, 95% confidence interval 1.01-1.05), but not in the left colon only (odds ratio=0.98, 95% confidence interval 0.97-1.00). In addition, patients with synchronous lesions in the right colon only tended to have adenomas in the right colon, while those with synchronous lesions in the left colon only tended to have adenomas in the left colon (each P value <0.05). CONCLUSION: The risk factors and status of concurrent adenomas of synchronous cancer cases varied according to tumour location, suggesting that the colonic site susceptible to neoplasia varies according to patient characteristics.

Persistent elevation of serum alanine aminotransferase levels leads to poor survival and hepatocellular carcinoma development in type 1 autoimmune hepatitis.

BACKGROUND: Although the prognosis of type 1 autoimmune hepatitis is generally good with immunosuppressive treatment, the disease progresses in some patients despite the treatment. The prognosis may be determined by the clinical course. AIM: To evaluate the long-term prognosis and assess the predictive factors for a serious event, including the development of hepatocellular carcinoma or death. METHODS: Sixty-nine patients with type 1 autoimmune hepatitis were prospectively followed up regularly, with a median follow-up period of 96 months (49-201 months). RESULTS: During the follow-up period, three patients (4%) developed hepatocellular carcinoma, and two of these three patients died. Another patient died of liver failure. The 10-year survival rate was 98%, and the 10-year hepatocellular carcinoma-free rate was 93%. The four patients experiencing a serious event received higher maintenance doses of corticosteroid during their follow-up periods than those did not. However, serum alanine aminotransferase levels during the follow-up period were higher in these four patients than in the others. CONCLUSIONS: Persistent elevation of serum alanine amniotransferase levels during the follow-up period, rather than factors existing prior to medical treatment is considered to be an important prognostic factor, and it is indicated that poor outcomes may result from the resistance to immunosuppressive treatment.

Endoscopic submucosal dissection for early gastric cancer: results and degrees of technical difficulty as well as success.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a new method for the curative treatment of early gastrointestinal neoplasms, which was developed in order to increase the en bloc and R0 resection rate, especially for lesions larger than 20 mm in diameter. Drawbacks of ESD include the fact that it is technically a substantially more difficult procedure and that it is associated with a higher perforation rate. A retrospective study was therefore carried out to analyze cases in relation to the procedure time and resection success, and these factors were correlated with the characteristics of the lesions. PATIENTS AND METHODS: From January 2002 to November 2005, 196 lesions in 185 patients with early gastric cancer were treated using ESD in our hospital. The rates of curative en bloc resection, the incidence of perforation, and the procedure times were analyzed in relation to lesion size (small, 20 mm or less in diameter; large, over 20 mm), location (upper, middle, or lower third of the stomach) and the presence or absence of ulceration. RESULTS: The rate of curative en bloc resection was 84 % (93 % of the lesions overall were resected in one piece), with a perforation rate of 6.1 % (all perforations were managed endoscopically) and a mean procedure time of 68 min. The rate of curative en bloc resection differed significantly depending on the location of the lesion (upper vs. middle vs. lower, 74 % vs. 77 % vs. 91 %; P < 0.05), as well as on the size of the lesion (> 20 mm vs. 20 mm or less, 59 % vs. 89 %; P < 0.0001). There were also significant differences in the mean procedure times in relation to the location of the lesion (upper vs. middle vs. lower, 105 min vs. 81 min vs. 45 min; P < 0.0001) and the size of the lesion (> 20 mm vs. 20 mm or less, 124 min vs. 55 min; P < 0.0001), as well as the presence of ulceration (positive vs. negative, 97 min vs. 65 min; P < 0.05). With regard to perforation rates, significant differences were also observed in relation to the location of the lesion (upper vs. middle vs. lower, 22.6 % vs. 2.8 % vs. 3.2 %; P < 0.0005) and size of the lesion (> 20 mm vs. 20 mm or less, 16.2 % vs. 3.8 %; P < 0.005). No local recurrences of curatively resected lesions (n = 119) were observed after a follow-up period of 1 year. CONCLUSIONS: The difficulty of ESD depends on the location and size of the lesion, as well as on the presence of ulceration. We would recommend that trainees should begin by carrying out ESD on lesions with a diameter of less than 20 mm without ulceration that are located in the lower third of the stomach.

Clinical features of Japanese male patients with type 1 autoimmune hepatitis.

BACKGROUND: Recently, unusual patients with autoimmune hepatitis, such as male patients, have increased. AIM: To assess clinical feature of Japanese males with type 1 autoimmune hepatitis compared with females. METHODS: We investigated consecutive 160 patients with type 1 autoimmune hepatitis, who consisted of 20 males and 140 females, with a median age of 55 (16-79) years. RESULTS: Compared with females, males had a lower frequency of definite diagnosis according to the revised scoring system proposed by the International Autoimmune Hepatitis Group (40% vs. 85%) and lower serum levels of immunoglobulin G [1932 (1085-3850) mg/dL vs. 2624 (1354-6562) mg/dL]. However, they were similar in age, form of clinical onset, symptomatic concurrent autoimmune disease, human leucocyte antigen DR status and frequency of cirrhosis at the time of diagnosis. The normalization of serum alanine aminotransferase levels within 6 months after the introduction of corticosteroid treatment was lower in males compared with females (73% vs. 93%). CONCLUSIONS: In male patients, a diagnosis of autoimmune hepatitis should be made carefully. In Japanese patients with a dominant frequency of human leucocyte antigen DR4, gender may affect the response to corticosteroid treatment.

Therapeutic efficacy of leukocytapheresis in a pregnant woman with severe active ulcerative colitis.

Leukocytapheresis has recently been used to induce remission in patients with ulcerative colitis (UC) who fail to respond to corticosteroids. We could not find a report in the literature on leukocytapheresis for UC with gestational exacerbation. We have recently encountered this unique condition and report the details here. A 30-year-old Japanese woman with left-sided severe UC was corticosteroid-dependent and had recurrence of the active disease during tapering of corticosteroid. She declined any dose increase and the use of any immunosuppressive agent because she was in the 13th week of pregnancy. Then, concomitant leukocytapheresis was performed without increasing the corticosteroid dose. Recovery was rapid and dramatic. Mucous and bloody stool decreased after the first session, and she had remission 2 weeks later. She underwent a total of four sessions without complications. After 6 weeks, she was discharged from our hospital and underwent maintenance treatment as an outpatient with mesalazine and corticosteroid tapering. Subsequently, she gave birth to a healthy baby girl by an uncomplicated vaginal delivery while keeping the remitted stage of UC.

Clinical characteristics of fulminant-type autoimmune hepatitis: an analysis of eleven cases.

BACKGROUND: Although a few adult cases of fulminant-type autoimmune hepatitis have been reported, their clinical features and prognosis have remained uncertain. AIM: To assess the clinical features and prognosis of patients with fulminant-type autoimmune hepatitis. METHODS: Eleven patients (10%) diagnosed with fulminant-type autoimmune hepatitis in accordance with the 1999 criteria of the International Autoimmune Hepatitis Group were analysed. RESULTS: All 11 patients were female, with a median age of 53 years. Five patients survived without liver transplantation, one received a liver transplantation, and five died without liver transplantation. Nine patients (82%) survived for 2 weeks or more following diagnosis, without liver transplantation. Except for the patient receiving a liver transplantation, serum total bilirubin levels measured during the clinical course were significantly higher in non-survivors than in survivors, although the accompanying serum alanine aminotransferase levels measured for the two groups were similar. Most significantly, serum total bilirubin levels in non-survivors worsened during days 8-15, while levels in survivors improved during the same period. CONCLUSIONS: The short-term prognosis for patients with fulminant-type autoimmune hepatitis may be good. However, patients whose serum total bilirubin levels worsen during days 8-15 should be considered for liver transplantation.

Evaluation of covered metallic stents in malignant biliary stenosis--prominent effectiveness in gallbladder carcinoma.

BACKGROUND/AIMS: The survival time of patients with unresectable malignant biliary stenosis and the patent period of metallic biliary stents are different in each disease. The efficacy of the covered metallic stent was analyzed according to the primary disease. METHODOLOGY: Seventy-three patients with bile duct carcinoma (12 cases), gallbladder carcinoma (22 cases), and pancreas carcinoma (39 cases) were retrospectively enrolled. Covered metallic stents were used in 42 patients and uncovered metallic stents in 31 patients. The patency of covered stents was compared with that of uncovered stents for each disease. RESULTS: The patent rate at 6 months after insertion was 80.6% (95% CI [72.6%, 88.6%]) for the covered stent, and 49.5% (95% CI [37.6%, 61.4%]) for the uncovered stent. The mean patent periods of the covered stent and the uncovered stent were 14.6 and 27.6 months for bile duct carcinoma (p=0.424), 12.7 and 3.0 months for gallbladder carcinoma (p=0.003), and 11.9 and 9.6 months for pancreas carcinoma (p=0.919), respectively. CONCLUSIONS: The covered metallic stent was the most effective in patients with gallbladder carcinoma.

Eradication of Helicobacter pylori increases platelet count in patients with idiopathic thrombocytopenic purpura in Japan.

BACKGROUND: The effect of Helicobacter pylori eradication on the platelet count in patients with thrombocytopenic purpura is controversial. In this multicentre study, we prospectively assessed the effect of H. pylori eradication therapy in idiopathic thrombocytopenic purpura patients. MATERIALS AND METHODS: Thirty-five consecutive patients with chronic idiopathic thrombocytopenic purpura (11 males and 24 females, a median age of 57) were assessed for H. pylori infection by use of a urea breath test. All patients received 1-week triple therapy (amoxicillin, clarithromycin, and lansoprazole) to eradicate H. pylori. At 6 months, idiopathic thrombocytopenic purpura patients with a platelet count recovery of greater than 100 x 10(9) L(-1) were defined as idiopathic thrombocytopenic purpura responders. RESULTS: Helicobacter pylori infection was observed in 25 (71%) of the 35 patients. All infected patients were cured. Eleven patients were identified as idiopathic thrombocytopenic purpura responders; 24 were considered nonresponders. Platelet counts improved by more than 100 x 10(9) L(-1) in 11 (44%) of the 25 patients cured of H. pylori infection, while none of the 10 patients H. pylori-negative patients experienced the same improvement (P = 0.015). Univariate analysis showed that H. pylori infection and its eradication were significant factors associated with platelet recovery (P = 0.015). CONCLUSIONS: Helicobacter pylori infection played a role in the pathogenesis of idiopathic thrombocytopenic purpura in approximately 30% of all patients assessed and 45% of the patients with H. pylori infection. Eradication of H. pylori in idiopathic thrombocytopenic purpura patients led to improved disease activity.

Coronary flow reserve after coronary intervention in similar in patients with preserved viability in previous myocardial infarction and in those with angina pectoris.

The relationship between coronary flow reserve (CFR) and viability in the infarcted myocardium has not been fully clarified. We measured coronary blood flow velocity immediately after coronary intervention (with percutaneous transluminal coronary angioplasty [PTCA] or stenting) in 38 patients with previous myocardial infarction and preserved viability and 48 with angina pectoris. CFR was calculated and was similar between the two patient groups. No differences in the incidence of post-intervention CFR > 2.0 were detected; there were no differences in post-intervention CFR between patients with preserved myocardial viability and those with angina pectoris who underwent PTCA. Coronary stenting reduced the percentage diameter stenosis in both groups compared with PTCA and slightly increased the post-intervention CFR. No differences were, however, detected in post-intervention CFR between patients with preserved myocardial viability and those with angina pectoris who underwent additional stenting. These results reveal that in patients with preserved myocardial viability, post-intervention CFR was restored to values similar to those in patients with angina pectoris.

A prospective randomised study of "covered" versus "uncovered" diamond stents for the management of distal malignant biliary obstruction.

BACKGROUND AND AIM: Covered self-expandable metal stents (EMS) were recently developed to overcome tumour ingrowth in conventional EMS. However, supporting evidence for the efficacy of covered EMS is lacking. PATIENTS AND METHODS: We enrolled 112 patients with unresectable distal biliary malignancies. They were randomly assigned to polyurethane covered (n = 57) or original diamond stent (n = 55). RESULTS: Stent occlusion occurred in eight patients (14%) after a mean of 304 days in the covered group, and in 21 patients (38%) after a mean of 166 days in the uncovered group. The incidence of covered EMS occlusion was significantly lower than that of uncovered EMS (p = 0.0032). The cumulative stent patency of covered stents was significantly higher than that of uncovered stents (p = 0.0066). No tumour ingrowth occurred in the covered group while it was observed in 15 patients in the uncovered group. In subgroup analysis, the cumulative patency of the covered EMS was significantly higher in pancreatic cancer (p = 0.0363) and metastatic lymph nodes (p = 0.0354). There was no significant difference in survival between the two groups. Acute cholecystitis was observed in two of the covered group and in none of the uncovered group. Mild pancreatitis occurred in five of the covered group and in one of the uncovered group. CONCLUSIONS: Covered diamond stents successfully prevented tumour ingrowth and were significantly superior to uncovered stents for the treatment of patients with distal malignant biliary obstruction. However, careful attention must be paid to complications specific to covered self-expandable metal stents, such as acute cholecystitis and pancreatitis.

Benefit of interferon therapy in hepatocellular carcinoma prevention for individual patients with chronic hepatitis C.

BACKGROUND: An increase in the incidence of hepatocellular carcinoma (HCC) in Japan since the 1980s suggests an imminent outbreak in other countries where viral spread occurred more recently. Interferon therapy for chronic hepatitis C, in general, has been shown to prevent HCC. AIMS: To determine the scale of benefit in individual patients. SUBJECTS: Histologically proven chronic hepatitis C patients in the Inhibition of Hepatocarcinogenesis by Interferon Therapy (IHIT) cohort (Ann Intern Med 1999;131:174), as updated in March 2003. METHODS: The lifetime risk for HCC was calculated based on HCC incidence rates, stratified by sex, age, fibrosis stage, and outcome of interferon therapy. The gain in HCC free survival was defined as the difference between expected HCC free survival with sustained virological response and that without. RESULTS: The gain in HCC free survival was greater when a patient was younger and fibrosis was more advanced. For example, a 30 year old male with F3 fibrosis gained 12.4 years by attaining sustained response while a patient with F1 fibrosis older than 60 years gained less than one year. For a treatment protocol with a given sustained response rate, prior estimation of the gain can be obtained by multiplying the calculated HCC free survival for responders by the response rate. CONCLUSIONS: The gain in HCC free survival may serve as an indicator of the benefit of interferon therapy in terms of HCC prevention and be useful in the consideration of indication and selection of treatment protocol for individual patients.

Histological analysis of the papilla after endoscopic papillary balloon dilation.

BACKGROUND/AIMS: Endoscopic papillary balloon dilation is an effective procedure in the management of bile duct stones and is believed to preserve the papillary function. The papillary architecture is also considered to be preserved. However, little is known about the effects of balloon dilation on papillary structure. The present study was conducted to elucidate these effects. METHODOLOGY: Since May 1994, endoscopic papillary balloon dilation was performed in 467 patients (407 patients for removal of bile duct stone, 57 for insertion of stent and 3 for baby cholangioscope). Of those, histological examinations were undertaken in 10 patients. The indications of endoscopic papillary balloon dilation were bile duct stone removal in 2 patients, stent insertion in 8. The specimens were obtained 2 to 63 weeks after endoscopic papillary balloon dilation during surgical operation in 6 patients and autopsy in 4 patients. Serial sections through the papilla were stained by hematoxylin and eosin and Masson's trichrome. The specimens were also obtained from 4 patients without biliary disease as control. RESULTS: No smooth muscle disruption nor architectural distortion was observed except for one patient who had mild disruption of smooth muscle caused by a biliary drainage tube. However, mild to moderate inflammation and fibrosis were seen in 9 patients and in 8, respectively. CONCLUSIONS: The papillary architecture is not affected by endoscopic papillary balloon dilation. This may imply that endoscopic papillary balloon dilation preserves papillary function.

A proton-pump inhibitor, rabeprazole, improves ventilatory function in patients with asthma associated with gastroesophageal reflux.

BACKGROUND: Treatment of gastroesophageal reflux (GER) with proton-pump inhibitors (PPI) improves symptoms of asthma in some patients. However, the effects of a PPI on ventilatory function are still controversial. In this study, we measured ventilatory function in asthma patients treated with a PPI in order to identify those in whom a therapeutic effect on asthma can be expected from the acid suppression. METHODS: From a cohort of 114 consecutive patients with bronchial asthma, 53 patients agreed to participate in the study and were treated with rabeprazole 20mg daily for 8 weeks during an asymptomatic, stable period with no exacerbations of their asthma. Of the 53 patients, 22 were diagnosed as GER on the basis of the QUEST questionnaire and endoscopic examination. The patients were monitored for improvement in ventilatory function. RESULTS: Four patients dropped out because of adverse drug reactions. All the patients with GER noted an improvement in reflux symptoms with PPI treatment. An improvement of more than 20% in peak expiratory flow (PEF) was observed in 8 of 21 GER patients but in none of the non-GER patients. Factors predictive of improvement in PEF with rabeprazole therapy were the QUEST score (odds ratio: 1.47, 95% CI: 1.06-2.04, P = 0.022) and steroid-dependency of asthma (odds ratio: 0.01, 95% CI: 0.001-0.31, P = 0.008). CONCLUSIONS: Treatment with rabeprazole is expected to ameliorate asthma in non-steroid-dependent patients who have symptomatic GER defined by the QUEST score.

The enzymatic basis for the conversion of nonfucosylated to fucosylated alpha-fetoprotein by acyclic retinoid treatment in human hepatoma cells: activation of alpha1-6 fucosyltransferase.

The purpose of the present study was to investigate the mechanism by which nonfucosylated alpha-fetoprotein (AFP) is converted to fucosylated AFP in human hepatoma cell lines exposed to acyclic retinoid (AR), an effective drug for the secondary prevention of hepatocellular carcinoma. AR treatment (100 microM) of HepG2 and Hep3B cells significantly increased the activity and mRNA levels of alpha1-6 fucosyltransferase (alpha1-6 FucT), the enzyme responsible for the fucosylation of AFP, leading to an increase in fucosylated glycoproteins as evidenced by lectin binding measurements. Lectin immunoelectrophoresis of AFP obtained from culture media indicated that the relative percentage of nonfucosylated AFP (L1 fraction) was decreased and alpha1-6 fucosylated AFP (L3 fraction) was increased in these hepatoma cell lines after treatment with AR. The total AFP levels were, however, markedly suppressed by AR treatment, and therefore the absolute L3 fraction on the basis of the total AFP present was extremely low. These results demonstrate that AR enhances the conversion of the L1 to the L3 fraction due to the activation of alpha1-6 FucT in human hepatoma cell lines despite clinical outcome with AR treatment and the L3 fraction of AFP. Even though the dramatic decrease in AFP is the limiting factor in the synthesis of the L3 fraction and, therefore, the absolute value of fucosylated AFP is extremely low, the conversion from L1 to L3 as judged by lectin immunoelectrophoresis represents a good marker for the progress of AR treatment.

Presence on human chromosome 10 of omeprazole-sensitivity gene whose product mediates CYP1A1 induction.

Previously, we showed that CYP1A1 expression can be induced by omeprazole (OP) in the human cell line HepG2, but not in the mouse cell line Hepa-1. Now we show induction of CYP1A1 by alpha-naphthoflavone (alphaNF) in Hepa-1 cells. This induction was inhibited by the tyrosine kinase inhibitor herbimycin A, but not by the aromatic hydrocarbon (Ah)-receptor antagonist PD98059, suggesting the presence of a ligand-independent signal-transduction pathway in the mouse cell line too. We utilized the lack of CYP1A1 induction by OP in Hepa-1 cells to map a putative human gene for OP-respon- siveness in cell hybrids produced by fusion of Hepa-1 and HepG2 cells. OP-induced CYP1A1 expression was detected in four out of the 32 Hepa-1 x HepG2 cell hybrids analyzed. To help identify the gene locus, a radiation-hybrid cell (E11) was constructed. Use of reverse-fluorescence in situ hybridization revealed that these five cell lines commonly retained human chromosome 10p. These results suggest that the human gene for OP-responsiveness is present on chromosome 10p.