A novel de novo point mutation of the OCT-binding site in the IGF2/H19-imprinting control region in a Beckwith-Wiedemann syndrome patient.

The IGF2/H19-imprinting control region (ICR1) functions as an insulator to methylation-sensitive binding of CTCF protein, and regulates imprinted expression of IGF2 and H19 in a parental origin-specific manner. ICR1 methylation defects cause abnormal expression of imprinted genes, leading to Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS). Not only ICR1 microdeletions involving the CTCF-binding site, but also point mutations and a small deletion of the OCT-binding site have been shown to trigger methylation defects in BWS. Here, mutational analysis of ICR1 in 11 BWS and 12 SRS patients with ICR1 methylation defects revealed a novel de novo point mutation of the OCT-binding site on the maternal allele in one BWS patient. In BWS, all reported mutations and the small deletion of the OCT-binding site, including our case, have occurred within repeat A2. These findings indicate that the OCT-binding site is important for maintaining an unmethylated status of maternal ICR1 in early embryogenesis.

Transcription factor AP-2beta inhibits expression and secretion of leptin, an insulin-sensitizing hormone, in 3T3-L1 adipocytes.

BACKGROUND: We have previously reported an association between the activator protein-2beta (AP-2beta) transcription factor gene and type 2 diabetes. This gene is preferentially expressed in adipose tissue, and subjects with a disease-susceptible allele of AP-2beta showed stronger AP-2beta expression in adipose tissue than those without the susceptible allele. Furthermore, overexpression of AP-2beta led to lipid accumulation and induced insulin resistance in 3T3-L1 adipocytes. RESULT: We found that overexpression of AP-2beta in 3T3-L1 adipocytes decreased the promoter activity of leptin, and subsequently decreased both messenger RNA (mRNA) and protein expression and secretion. Furthermore, knockdown of endogenous AP-2beta by RNA-interference increased mRNA and protein expression of leptin. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed specific binding of AP-2beta to leptin promoter regions in vitro and in vivo. In addition, site-directed mutagenesis of the AP-2-binding site located between position +34 and +42 relative to the transcription start site abolished the inhibitory effect of AP-2beta. Our results clearly showed that AP-2beta directly inhibited insulin-sensitizing hormone leptin expression by binding to its promoter. CONCLUSION: AP-2beta modulated the expression of leptin through direct interaction with its promoter region.

Age-related and intelligence-related differences in implicit memory: effects of generation on a word-fragment completion test.

In two experiments, subjects either read a bracketed word in a sentence or generated a word in response to its definition. A word-fragment completion test was then carried out. In Experiment 1, children's priming under the generate condition was substantial, as compared with baseline performance, but was significantly lower than that under the read condition, whereas there was no difference in adults' priming between these two conditions. Furthermore, prior generation induced an age-related increase in priming despite no age difference under the read condition. In Experiment 2, mentally retarded persons exhibited a profile similar to that of children. These results suggests that there are two different components in implicit memory, one that shows no developmental difference and heavily relies on perceptual processing and the other that shows an age-related or intelligence-related increase and heavily relies on conceptual processing.

[The effects of fitness-type exercise on iron status and hematological status for female college students].

Forty-two female college students underwent fitness-type exercise over a 13 week period. The students exercised an average of two times a week for 30 minute periods at 50% levels of VO2 . max. Iron status and hematological laboratory data were monitored at three points in time; at the initiation of exercise, at the termination of exercise and 3 months later. Serum ferritin levels in a third of the students were lower than 12ng/ml. Red blood cell counts decreased during exercise, and returned to the pre-exercise levels 3 months later. The number of circulatory reticulocytes and mean corpuscular hemoglobin concentration were increased significantly after the exercise and the effects were still observed 3 months later, independent of the iron status. In the lower ferritin group, erythropoietin levels decreased significantly during the post-exercise period. The average serum ferritin levels while showing no significant changes during exercise, increased significantly during the post-exercise period, in the normal ferritin group. We discussed possible mechanisms, among them iron metabolism, by which physical training may facilitate erythropoiesis. However, no definite conclusions have been reached.

[Effects of breathing high concentrations of oxygen on changes in blood indices during bicycle exercise].

The purpose of this study is to examine effects of hyperoxic gas mixtures on changes of blood indices during bicycle exercise of human. Oxygen-enriched gases (30% O2) were inspired during the ramp load exercise of 25 watt/min. Changes of blood indices were analyzed with Sequential Multiple Analyzer with the computer (SMAC). The improvement of exercise performance were discussed about relationship between function of hyperoxic gas and physiological mechanism. Three experimental conditions were set as follows (I) 30% O2 +N2 gases balance, (II) air (21% O2), and (III) 30% O2 +2% CO2 +N2 gases balance. Arterial blood were sampled from the radial artery of the forearm in order to analyze following items; 1) pH level, PaO2, PaCO2, and HCO3 of these blood gases, 2) Blood sugar, TG, and F-CH of the blood contents, 3) red blood corpuscle, white blood corpuscle, Hb, and Ht values, 4) LDH, CK, GOT, and GPT of the blood enzymes, 5) TP, ALB, Na, K, Ca and Cl of the electric ions. In the case of inspiring hyperoxic gases, the recovery rate of blood indices increased after this ramp load exercise remarkably, and the whole exercise metabolism were removed from acidosis tendency to alkalosis value of the resting condition significantly. At hyperoxic experimental conditions, the blood sugar and oxygen consumption were much more decreased than these at normal oxygen content one during both states of exercise and recovery times. These data of the blood indices would support strongly to the hypothesis that improvement of oxygen delivery should be depended upon the enhanced performance with the hyperoxic gases. There might be effects of the hyperoxia on the cellular metabolism and on function of the vascular muscle during those aerobic exercise.