Predictive Factors for the Development or Regression of Fatty Liver in Japanese Adults

Fatty liver is commonly associated with alcohol or metabolic syndrome. We aimed to examine the longitudinal aspects of fatty liver, and clarify the independent predictors for the development or regression of fatty liver. In the present study, the clinical features of 1578 Japanese adults (1208 men and 370 women; 35 to 69 years of age) who visited our center both in 2000 and 2007–2008 were recorded and compared, including liver status diagnosed by ultrasonography. Of the 1578 participants, 217 (13.8%) showed fatty liver development, and 74 (4.7%) showed fatty liver regression. Logistic regression analysis revealed that body mass index and percentage body fat were strongly associated with the development or regression of fatty liver. Metabolic syndrome-related disorders such as serum levels of total cholesterol, triglyceride, uric acid, and fasting blood glucose were also associated with clinical course to some degree. However, the history of alcohol intake, the presence of metabolic syndrome, blood pressure, and habitual physical exercise were not independent predictors for the development or regression of fatty liver. Our present data suggest that control of body weight in men and the percentage body fat in women are particularly important for the prevention or treatment of fatty liver.     

Cianidanol therapy for HBe-antigen-positive chronic hepatitis: a multicentre, double-blind study

The effect of cianidanol on the HBeAg/anti-HBe system in 338 patients with HBeAg-positive chronic hepatitis was studied in a double-blind, randomised, placebo-controlled, multicentre clinical trial. 174 patients received cianidanol in a daily dose of 1.5 g for 2 weeks, followed by 2.25 g for a further 14 weeks. 164 patients received a placebo for the same period: patients were followed up for a further 8 weeks. HBeAg and anti-HBe antibody titers were measured by R.I.A. at 4-week intervals and the results were expressed as a "cut-off index" and "inhibition percent", respectively. Liver function tests were also monitored at the same intervals. The HBeAg titer decreased by at least 50% in 44 of 144 cases treated with cianidanol (21 of 140 cases treated with placebo). The difference was significant (p less than 0.01). The HBeAg disappeared in 16 of the cianidanol cases and four of the placebo (p less than 0.05) and a seroconversion was observed in six cianidanol patients and three placebo patients. The mean HBeAg titer in the cianidanol group was significantly lower than that in the placebo group at the end of the 16 weeks of therapy (p less than 0.05). The patients whose HBeAg titer was lowered were largely those with chronic active hepatitis and had higher initial values of SGPT, SGOT and gamma-globulin than the patients whose HBeAg titers remained unchanged. The mean values for these liver function tests also fell significantly in the former sub-group. The drug was well tolerated, the only notable side effect being a transient febrile reaction in 13 patients. It is concluded that cianidanol is a useful and well-tolerated drug for improving the HBeAg/anti-HBe system in patients with HBeAg-positive chronic active hepatitis.     

Analysis of K-<Emphasis Type="Italic">ras</Emphasis> Codon 12 Mutation in Flat and Nodular Variants of Serrated Adenoma in the Colon

PURPOSE: The developmental process of serrated adenomas is obscure, and the importance of genetic alterations has not been elucidated clearly. The possibility that the developmental process and genetic alterations of serrated adenomas could differ from those of ordinary tubular adenomas was explored in this work. METHODS: Serrated adenomas were obtained by endoscopic resection (n = 57) and divided into two groups: flat (n = 10) and nodular (n = 47). Mutation of the K-ras gene was analyzed by enriched polymerase chain reaction–enzyme-linked mini-sequence assay, which can detect not only the presence of a mutation but also the mutation type of K-ras codon 12 with high sensitivity. Methylation-specific polymerase chain reaction was performed with specific primers for the DNA repair gene O6-methylguanine-DNA methyltransferase. RESULTS: Serrated adenomas located in the rectum were more likely to have a K-ras mutation (9/12, 75 percent), whereas serrated adenomas of the flat type were less likely to have one (1/10, 10 percent). Furthermore, nodular serrated adenomas that occurred in the rectum possessed a high frequency of K-ras gene codon 12 point mutation (8/10, 80 percent) despite an overall frequency of 46.8 percent (22/47). A mutation of the K-ras codon 12 gene was detected in 23 (40.4 percent) of 57 serrated adenomas. Three types of point mutations of codon 12 were detected, with the mutation of GAT being observed most frequently. CONCLUSIONS: This study shows that development of nodular serrated adenomas may depend on the mutation of the K-ras codon 12 gene, whereas development of flat serrated adenomas may not. Additionally, serrated adenomas that occur in the rectum are closely related to the mutation of the K-ras codon 12 gene. K-ras mutations in serrated adenomas may be unaffected by the epigenetic silencing of O6-methylguanine-DNA methyltransferase by promoter hypermethylation.     

Different outcomes of vertical transmission of hepatitis C virus in a twin pregnancy

The risk of vertical transmission of hepatitis C virus (HCV) from mother to infant has been well documented, but the exact mode of transmission is still unclear. In a set of monochorionic diamniotic monozygous twins, only the second baby was infected with HCV from the mother who was positive for serum HCV-RNA. The babies had an uncomplicated vaginal delivery 3 min apart and they were both bottle fed from the outset. The second baby developed clinical hepatitis that persisted to 30 months follow up. The intrauterine environment should have been identical for these twins, and therefore, the maternal HCV factors, including viral load are not the sole determining factors for mother-to-infant transmission of HCV.     

Successful treatment of spinocerebellar ataxia 6 with medicinal herbs

A case of familial spinocerebellar ataxia 6 with typical symptoms is presented. A 60-year-old Japanese female suffered from gait disturbance, ataxia and dizziness. Head magnetic resonance imaging revealed a typical atrophic image in cerebellum. Genetic tests revealed an expanded allele of 22 CAG repeats at the spinocerebellar ataxia type 6 locus. She was diagnosed with spinocerebellar ataxia 6. Her mother was also diagnosed with the same disease. A mixture of 18 medicinal herbs (modified Zhengan Xifeng Tang) was given according to the differential diagnosis based on the guidelines of traditional Chinese medicine. All of the symptoms were remarkably improved after 60 days of the herbal treatment. One year after discontinuation of the treatment, she complained of gait ataxia. She was treated with the modified Zhengan Xifeng Tang for 60 days. Gait ataxia was markedly improved by the second treatment. Fifteen months after discontinuation of the second treatment, she complained of gait ataxia again. The same remedy was given for 60 days. Gait ataxia was remarkably reduced again. The results may imply therapeutic potential of the medicinal herbs for spinocerebellar ataxia 6.     

Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians

OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. RESULTS: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.     

Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast

It is well known that sex steroids play important roles in the development of invasive ductal carcinoma (IDC) of the human breast. However, biological significance of sex steroids remains largely unclear in ductal carcinoma in situ (DCIS), regarded as a precursor lesion of IDC, which is partly due to the fact that the intratumoral concentration of sex steroids has not been examined in DCIS. Therefore, in this study, we first examined the intratumoral concentrations of estradiol and 5alpha-dihydrotestosterone (DHT) using liquid chromatography/electrospray tandem mass spectrometry in DCIS. Intratumoral concentrations of both estradiol and DHT were threefold higher in DCIS than non-neoplastic breast tissues and estrogen-producing enzymes (aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1)), and androgen-producing enzymes (17betaHSD5 and 5alpha-reductase type 1 (5alphaRed1)) were abundantly expressed in DCIS by real-time PCR and immunohistochemical analyses. The intratumoral concentration of DHT was significantly lower in IDC than DCIS, while the expression of aromatase mRNA in carcinoma cells and intratumoral stromal cells was significantly higher in IDC than those in DCIS. Immunohistochemistry for sex steroid-producing enzymes in DCIS demonstrated that 5alphaRed1 immunoreactivity was positively correlated with Ki-67 labeling index and histological grade and was also associated with an increased risk of recurrence in patients with DCIS examined. Results of our study suggest that intratumoral concentrations of estradiol and DHT are increased in DCIS, which is possibly due to intratumoral production of these steroids. Therefore, estradiol and DHT may play important roles in the development of DCIS of the human breast.