Kazuo Tobe

Relationship between serum leptin and fatty liver in Japanese male adolescent university students

Relationship between serum leptin and fatty liver in Japanese male adolescent university students

Relationship between periodontitis and hepatic abnormalities in young adults.

Abstract Objective. Obesity has been implicated as a risk factor for periodontitis and non-alcoholic fatty liver disease (NAFLD). In NAFLD, elevated alanine aminotransferase (ALT) is associated with obesity. Although a possible interrelationship between liver function and periodontitis has been reported among the middle-aged population, the correlation in young adults is little known. This study was designed to investigate the relationship between ALT and the presence of periodontitis in university students in Japan. Material and methods. Medical and oral health data were collected in a cross-sectional examination conducted by the Health Service Center of Okayama University. Systemically healthy, non-smoking students aged 18 and 19 years old (n = 2225) were included. The protocol of the United States National Health and Nutrition Examination Survey was applied. Subjects with probing pocket depth ≥ 4 mm were defined as having periodontitis. Logistic regression analysis was used to estimate the association between ALT, body mass index and periodontitis. Results. The number of subjects with periodontitis was 104 (4.7%). In males, having periodontitis was significantly associated with an increased level of ALT (≥ 41 IU/l) in logistic regression analysis (adjusted odds ratio 2.3; 95% confidence interval 1.0–5.2; p < 0.05). However, there was no significant association between periodontitis and ALT in female students. Conclusions. Elevated ALT could be a potential risk indicator for periodontitis among young males. Monitoring hepatic abnormalities to prevent periodontitis must be better understood, even in the young adult population.

Whole blood interferon-gamma assay for baseline tuberculosis screening among Japanese healthcare students.

Background The whole blood interferon-gamma assay (QuantiFERON-TB-2G; QFT) has not been fully evaluated as a baseline tuberculosis screening test in Japanese healthcare students commencing clinical contact. The aim of this study was to compare the results from the QFT with those from the tuberculin skin test (TST) in a population deemed to be at a low risk for infection with Mycobacterium tuberculosis. Methodology/Principal Findings Healthcare students recruited at Okayama University received both the TST and the QFT to assess the level of agreement between these two tests. The interleukin-10 levels before and after exposure to M tuberculosis-specific antigens (early-secreted antigenic target 6-kDa protein [ESAT-6] and culture filtrate protein 10 [CFP-10]) were also measured. Of the 536 healthcare students, most of whom had been vaccinated with bacillus-Calmette-Guérin (BCG), 207 (56%) were enrolled in this study. The agreement between the QFT and the TST results was poor, with positive result rates of 1.4% vs. 27.5%, respectively. A multivariate analysis also revealed that the induration diameter of the TST was not affected by the interferon-gamma concentration after exposure to either of the antigens but was influenced by the number of BCG needle scars (p = 0.046). The whole blood interleukin-10 assay revealed that after antigen exposure, the median increases in interleukin-10 concentration was higher in the subgroup with the small increase in interferon-gamma concentration than in the subgroup with the large increase in interferon-gamma concentration (0.3 vs. 0 pg/mL; p = 0.004). Conclusions/Significance As a baseline screening test for low-risk Japanese healthcare students at their course entry, QFT yielded quite discordant results, compared with the TST, probably because of the low specificity of the TST results in the BCG-vaccinated population. We also found, for the first time, that the change in the interleukin-10 level after exposure to specific antigens was inversely associated with that in the interferon-gamma level in a low-risk population.

ELECTRON MICROSCOPY OF LIVER LESIONS IN PRIMARY BILIARY CIRRHOSIS

An 80 μm bile duct with typical features of chronic non‐suppurative destructive cholangitis was examined by electron microscopy. Many inflammatory cells, including lymphocytes, macrophages and plasma cells infiltrated among epithelial cells of the bile duct. Epithelial cells were compressed and deformed by infiltrating lymphocytes. These lymphocytes were in contact with epithelial cells at small points or large areas. The intercellular distance was about 10 or 20 nm at the contact areas. The mode of contact and intercellular distance coincided with the results of in vitro experiments on lymphocyte cytotoyicity against target cells. Some epithelial cells in contact with lymphocytes showed degenerative changes. Necrotic changes were observed in bile duct epithelial cells undergoing emperipolesis. The invading lymphocyte in the epithelial cell had osmiophilic substances on the surface. These sites of emperipolesis seem to be the areas of lymphocyte cytotoxicity against epithelial cells.

Regulation of circulating immune complexes by complement receptor type 1 on erythrocytes in chronic viral liver diseases.

Background and aim: Complement receptor type 1 (CR1) is a transmembrane protein, and human erythrocyte CR1 (E-CR1) is involved in the transport of circulating immune complexes (IC) from the circulation to the reticuloendothelial system, including the liver and spleen. In chronic viral hepatitis, increased levels of IC containing viral particles and an association with various extrahepatic manifestations have been reported. However, regulatory mechanisms for IC levels are not fully understood. Patients/subjects and methods: We analysed IC, E-CR1, and quantitative polymorphism of the CR1 gene in 149 patients with chronic viral liver diseases and in 64 normal blood donors using an enzyme linked immunosorbent assay, radioimmunoassay, and polymerase chain reaction-restriction fragment length polymorphism, respectively. We also analysed the effect of CR1 gene polymorphism on IC binding to E-CR1 using molecular methods. Results: E-CR1 levels in patients with chronic hepatitis and chronic viral liver diseases as a whole correlated inversely with increased levels of IC. Moreover, significantly high levels of IC were observed in patients with chronic hepatitis C (CH-C) who were homozygous for the E-CR1 low density allele. We also found low levels of E-CR1 in liver cirrhosis and CH-C but not in CH-B. Low levels of E-CR1 in CH-C were observed, even after considering the polymorphism of the CR1 gene. Finally, we demonstrated CR1 gene polymorphism dependent binding of hepatitis virus containing IC. Conclusions: Our results emphasise the important role of E-CR1 in clearance of IC from the circulation and the acquired, rather than inherited, decrease in E-CR1 in chronic viral liver diseases, especially of type C.

Relationship between adrenomedullin and vasopressin-aquaporin system under general anesthesia.

Aim: The roles of adrenomedullin (AM) in body fluid balance under general anesthesia were investigated. Methods: Time course changes in plasma osmolality, AM, arginine vasopressin (AVP), and urinary aquaporin 2 (AQP2) in 17 patients undergoing abdominal surgery under general anesthesia were examined. Results: Increases in plasma AM levels were observed in parallel with increases in the levels of urinary AQP2/creatinine (Cr) before induction and 90 and 180 min after initiation of anesthesia. Significant correlations between plasma AM and urinary AQP2/Cr (r = 0.62, p < 0.0001) as well as urinary AVP/Cr and AQP2/Cr (r = 0.60, p < 0.0001) were uncovered. Multivariate stepwise analysis identified plasma AM as the critical independent factor affecting urinary AQP2/Cr level. Conclusion: A novel correlation of AM and AQP2 which overlays an AVP-AQP2 system may play a key role in fluid homeostasis during general anesthesia.

Testosterone modulates serum leptin concentrations in a male patient with hypothalamic hypogonadism

Serial measurements of body mass index (BMI), serum concentrations of testosterone (T), estradiol (E) and leptin (L) were performed before and after gonadotropin (Gn) therapy in an 18-year-old male subject (BMI 25.4 kg/m2) with idiopathic hypothalamic hypogonadism (IHH). We also measured the BMI and serum concentrations of L in 99 age-matched healthy subjects. Serum L correlated significantly with BMI in control subjects (r=0.84, p<0.0001). Baseline serum concentrations of L in our case were markedly high and both T and E were very low, but Gn therapy resulted in a gradual decrease in L and improvement in T and E, finally reaching the control levels of BMI-matched subjects. Our results demonstrate that T is a powerful negative modulator of serum L independent of BMI in conditions associated with low T levels, such as IHH.

Langerhans Cells among Bile Duct Epithelial Cells in Chronic Liver Disease

Langerhans cells were found among bile duct epithelial cells in a biopsy specimen from a patient with chronic liver disease showing cholangitic features. The bile duct was 90 μm In diameter and surrounded with mononuclear cell infiltration. Under the electron microscope, the cell had a clear cytoplasm and contained a deeply indented nucleus, a centriole, well‐developed Golgi complexes and many rod‐shaped bodies (Birbeck granules).

Electron microscopy of granulomatous lesions of the liver in primary biliary cirrhosis.

Three granulomas in the portal tract and 9 bile ducts with typical features of chronic non‐suppurative destructive cholangitis (CNSDC) associated with dispersed epithelioid.cells were examined by electron microscopy in 10 patients with primary biliary cirrhosis (PBC). Vesicular epithelioid cells, which contained numerous single‐membrane bound vesicles, predominated in the granulomas. On the other hand, immature epithelioid cells and activated macrophages were more often observed near epithelial cells of the bile ducts with CNSDC than in the granulomas. These macrophages seemed to be activated by epithelial cells of the bile ducts and develop into epithelioid cells. Honeycomb‐like membranous labyrinths containing electron dense substances were frequently observed in epithelioid cells and were likely a special form of phagosome. The substances in the labyrinths seemed to be derived from organellae of necrotic cells and extracellular interstitial tissues. Subplas‐malemmal linear densities (SPLD) were observed at the cytoplasmic boundary and at intracytoplasmic membranous labyrinth. The roles of SPLD were discussed. ACTA PATHOL. JPN. 35 : 1309–1318, 1985.

Clinical significance of low or negative titer of antibody to hepatitis B core antigen during the course of chronic hepatitis B virus infection in adolescents.

SummaryAntibody to hepatitis B core antigen (anti-HBc) was measured by radioimmunoassay in 127 asymptomatic hepatitis B surface antigen (HBsAg) carriers (ASC; mean age 19) who had normal serum alanine aminotrasferase (ALT) levels and 16 patients with chronic hepatitis B (CH; 19). All 16 CH patients, who were positive for hepatitis B e antigen (HBeAg) and 5 ASC cases who were negative for both HBeAg and its antibody (anti-HBe), had high anti-HBc titers. Anti-HBc titers in 27 (56.3%) of the 48 HBeAg-positive ASC and 18 (24.3%) of the 74 anti-HBe-positive ASC were relatively low. Two of the ASC were HBeAgpositive/ anti-HBc-negative. In a follow-up study of the 19 HBeAg-positive ASC with low or negative anti-HBc titers, 5 had abnormal serum ALT levels and increased anti-HBc titers. In contrast, in the other 14 of these subjects, serum ALT levels remained normal and the low anti-HBc titers remained unchanged and/or decreased. The serological profile of HBsAg-positive/low or negative anti-HBc titer and increased anti-HBc titer with abnormal serum ALT levels are not necessarily exceptional in HBeAg-positive adolescent ASC. It is suggested that anti-HBc is associated with the liver damage that occurs before adolescence in chronic hepatitis B virus infection.