CD57+ T cells augment IFN-gamma production in a one-way mixed lymphocyte reaction and their expansion after stem cell transplantation in paediatric patients.

To clarify the immune response of CD57+ T cells (most of them are CD8+) in peripheral blood (PB) against alloantigens in order to elucidate the T helper 1 (Th 1) immune response, we assessed the role of CD57+ T cells in IFN-gamma (one of the representative Th 1 cytokines) production in a one-way mixed lymphocyte reaction (MLR). In this study, we showed that CD57+ T cells in responder cells were essential for effective IFN-gamma production in allogeneic MLR due partly to the augmentation of the alloresponse of regular T cells. Furthermore, IFN-gamma production in MLR correlated with the proportions of CD57+ T cells in PB regardless of the responders' age. We also showed that the extent of the expansion of CD57+ T cells in paediatric patients after haematopoietic stem cell transplantation (HSCT) was markedly lower than that in adult patients. In addition, CD57+ T cells purified and activated with a combination of cytokines showed a greater cytotoxicity than regular T cells against human umbilical vein endothelial cells. Because IFN-gamma production in one-way MLR is a useful predictor of graft-versus-host disease (GVHD), especially in the acute phase that occurs after allogeneic HSCT, our findings suggested that CD57+ T cells play a role in the development of GVHD and thus may explain the reason as to why a higher donor age is associated with an increased risk of developing GVHD while, in addition, the incidence of severe GVHD in paediatric patients is lower than that in adult patients.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.

Long-term outcome of chronic hepatitis B in adolescents or young adults in follow-up from childhood.

BACKGROUND: It has not yet been defined whether children with chronic hepatitis B are likely to develop severe liver disease in the future. The purpose of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood. METHOD: Fifty-two children in the age range of 0 to 15 years who were positive for hepatitis B surface antigen and hepatitis B e antigen in serum for at least 6 months were enrolled in this study. In the majority of the 52 children, hepatitis B virus infection was acquired by perinatal transmission. All 52 showed abnormal liver function test findings for more than 6 months before enrollment, and the subjects were followed up longitudinally for 3 to 22 years (mean, 11 years). They are now more than 15 years of age (15-27 years old). RESULTS: During the follow-up period, 26 (50%) children had spontaneous seroconversion to anti-hepatitis B e. Serum levels of alanine aminotransferase normalized in these 26 children. In one child of these children, hepatocellular carcinoma developed at the age of 21 years, 16 years after seroconversion, although his liver function profiles remained normal. The other 26 children remained hepatitis B e antigen positive, most with unchanged biochemical features. Sixteen (62%) children among these 26 children were treated with interferon-alpha. Eleven (69%) children had seroconversion to anti-hepatitis B e within the first year after the cessation of therapy. Hepatocellular carcinoma developed in 1 of these 11 children at the age of 16 years, 6 years after interferon therapy. Thus, hepatocellular carcinoma developed in two children in an anti-hepatitis B e positive phase. CONCLUSION: All children carrying hepatitis B surface antigen should be observed carefully to monitor the possible development of hepatocellular carcinoma, especially in the antihepatitis B e-positive phase after spontaneous seroconversion or even after interferon treatment.

Study to establish normal values for portal vein blood flow in children using a duplex ultrasound system.

Portal vein blood flow in healthy children was measured using a duplex ultrasound system consisting of a B mode linear scanner and a single Doppler transducer. Portal blood flow volume (PBFV) correlated with age, height, weight and body surface area. Increases in PBFV with age were greater in boys than girls. A correlation was noted between the diameter of the portal vein and PBFV (r = 0.89). However, the maximum portal blood flow velocity (Vmax) did not correlate with age, height, weight or body surface area. Increases in PBFV in accordance with physical development was thought to depend mainly on widening of the portal vein and not on acceleration of portal blood flow velocity. The formula for calculating PBFV by multivaliate statistical analysis is as follows: PBFV(ml/min) = 30.1 x age(yrs) - 1.07 x height(cm) = 3.31 x weight(kg). Portal vein flowmetry using a duplex ultrasound system may be useful for evaluation of the hepatic circulation in children.

Changes of anti-HB core antibody in children with positive HB surface antigen.

To elucidate the clinical courses of children chronically infected with HB virus (HBV), RIA values of anti-HBc were surveyed in 88 cases with positive HBs antigen. Among 56 children with positive HBe antigen, 20 had negative, indefinite or low titers of anti-HBc, and 18 (90%) of them had no liver malfunction. Out of 30 cases with abnormal liver function tests, 28 (93%) had high titers of anti-HBc. Follow-up study for a period of over 12 months reveals that serum HBe antigen disappeared in 10 out of the 40 cases who were positive for this antigen. All of the 10 cases had liver malfunction and high levels of anti-HBc. Among 12 children with initially positive anti-HBe, five had high titers of anti-HBc. Out of 13 children who once had high levels of anti-HBc, 3 showed reduction in titers of anti-HBc during the follow-up period in accordance with decrease in activity of hepatitis. Four out of 16 who initially had HBe antigen and low titers of anti-HBc showed high titers of anti-HBc during the observation period, while only one of 33 who had HBeAg and a high titer of anti-HBc went to the low titer group of anti-HBc, though continuously positive for HBe antigen. We presume that high levels of anti-HBc indicate previous or current liver damage due to HBV infection, while low titers of anti-HBc indicate that HBV-derived liver damage has not yet occurred or that a long time has passed since the last episode of liver damage subsided.

Effect of diabetes on the free polyol pattern in cataractous lenses.

To obtain information about the effects of lenticular polyols on the prevention, initial stages, and development of diabetic cataracts, we identified and determined with gas-liquid chromatography or gas-liquid chromatography/mass spectrometry eight polyols in cataractous lenses of non-insulin-dependent diabetes mellitus patients and nondiabetic subjects. In the diabetics' lenses, the concentrations of polyols (e.g., sorbitol, fructose, mannitol, and adonitol) were higher than in the nondiabetics' lenses, whereas the concentration of 1-deoxyglucose was lower. The mean concentration of myo-inositol in lenses of diabetics was lower than that of nondiabetics, but this difference was statistically not significant. The total content of eight polyols in the diabetics' lenses did not differ significantly from that in the nondiabetics. In the lenses of diabetics, the content of glucose correlated positively with that of adonitol, fructose, and sorbitol. In the lenses of nondiabetics, the content of glucose correlated positively with that of mannitol and inversely with that of 1-deoxyglucose and myo-inositol. In diabetics, hemoglobin A1 (%) correlated positively with the concentration of adonitol in the lenses and inversely with the concentration of lens myo-inositol; however, it did not correlate with the concentration of glucose in lenses. Regulation of both the metabolism of lenticular polyols and the pattern of polyols in serum may be necessary for normalizing lenticular polyol content.