ヒストン修飾酵素JMJD1AとSWI/SNF複合体による熱産生遺伝子の発現機構に関する研究

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 酒井 寿郎, 東京大学教授 児玉 龍彦, 東京大学教授 油谷 浩幸, 東京大学教授 伊庭 英夫, 東京大学特任准教授 田中 十志也University of Tokyo(東京大学

The effect of Jati Belanda (Guazuma ulmifolia Lamk) leaves extract on histopathology of rat’s kidney

Introduction: “Jati Belanda”(Guazumaulmifolia Lamk) is a common tropical plant that its leaves extract has long been used traditionaly to treat some tropical diseases and also to reduce body weight as slimming herbs in some of tropical countries. However, the side effect of the administration of“Jati Belanda”leaves extract on themost sensitive excretory organ, the kidney is still notwell documented.Objectives: To study the effect of the oral administration of “Jati Belanda” (Guazuma ulmifolia Lamk.) leaves extract on the histopathology of the kidney.Methods: The study was a pretest and posttest experimental design using four groups of three rat. The study was a pretest and posttest experimental design using four groups of three rat. The exctract of “Jati Belanda” leaves was prepared by boilling of a certain weight of dried “Jati Belanda” leaves in 200 ml of destilated water until the volume of the water became 100 ml. Rat in group I was a control group which were given destilated water, group II were given 0,53 g/100 ml extract, group III were given 1,06 g/100 ml extract and group IV were given 2,12 g/100 ml extract, and the histopathological changes of the rat kidney before, 1 day and 7 days after administration of the extract were compared.Results: Histopathological changes were found in rat kidney following single dose treatment while the control group was not. At one day after administration, mesangial cells proliferation was found in 33,3% of rat in group II and 33,3% of rat in group III, while congestion of blood vessels was found in 66,6% of rat in group III and all rats at the highest dose, group IV. Meanwhile, after 7 days, congestion of micro-vessels was found in all rats of group II, III and IV. Moreover, necrosis of cells was found in 33,3% of rat in group III and infiltration of inflammation cell was found in 66,6% of rat in group IV.Conclusion: A single dose treatment of “Jati Belanda” leaves extract caused histopathological changes on rat kidney. The changes include increased in mesangial cell proliferation, congestion of renal blood vessels in the glomerulus or tubulus, inflamatory cell infiltration and tissue necrosis.Keywords: herbal medicine, “Jati Belanda” Guazuma ulmifolia Lamk. Histopathology, kidney

Seasonal changes in the antibody responses against Plasmodium falciparum merozoite surface antigens in areas of differing malaria endemicity in Indonesia.

BACKGROUND: The transmission of malaria in Indonesia is highly heterogeneous spatially and seasonally. Anti-malaria antibody responses can help characterize this variation. In the present study antibody responses to Plasmodium falciparum MSP-1 and AMA-1 were measured to assess the transmission intensity in a hypo-endemic area of Purworejo and a meso-endemic area of Lampung during low and high transmission seasons. METHODS: Filter-paper blood spot samples collected from Purworejo and Lampung by cross-sectional survey during high and low transmission season were stored at -20°C. Indirect ELISA assays were carried out using PfMSP1-19 and PfAMA1 antigens. A positivity threshold was determined by samples from local unexposed individuals, and the differences in seroprevalence, antibody level and correlation between antibody level and age in each site were statistically analysed. RESULTS: Prevalence of antibodies to either PfMSP1-19 or PfAMA1 was higher in Lampung than in Purworejo in both the low (51.3 vs 25.0%) and high transmission season (53.9 vs 37.5%). The magnitude of antibody responses was associated with increasing age in both sites and was higher in Lampung. Age-adjusted seroconversion rates showed an approximately ten-fold difference between Lampung and Purowejo. Two different seroconversion rates were estimated for Lampung suggesting behaviour-related differences in exposure. In both settings antibody responses to PfMSP1-19 were significantly lower in the low season compared to the high season. CONCLUSION: Seasonal changes may be detectable by changes in antibody responses. This is particularly apparent in lower transmission settings and with less immunogenic antigens (in this case PfMSP1-19). Examination of antibody levels rather than seroprevalence is likely to be a more sensitive indicator of changes in transmission. These data suggest that sero-epidemiological analysis may have a role in assessing short-term changes in exposure especially in low or seasonal transmission settings

Correlation between Apolipoprotein B/Apolipoprotein A-I Ratio with Atherogenic Index of Plasma among Acute Myocardial Infarction Patients

BACKGROUND: Acute myocardial infarction (AMI) is the most common cause of death in the world. One preventive attempt to reduce AMI is early detection of blood lipid profile. A simple method of lipid profile assessment is the measurement of atherogenic index of plasma (AIP), meanwhile more accurate method of lipid profile assessment is the measurement of apolipoprotein B/apolipoprotien A-I (ApoB/ApoAI) ratio. However, whether both measurements are interchangeable is need to be investigated. This study aims to investigate the correlation between AIP value and ApoB/ApoAI ratio in patients with AMI. METHODS: The study design was cross-sectional study. The blood samples of consecutively enrolled AMI patients had been selected after inclusion and exclusion criteria. The blood samples were taken within 24 hours of patient admission to the hospital. The blood concentration of high-density lipoprotein (HDL) and triglycerides (TG) were measured using turbidimetric method. The AIP was calculated as logarithmic of TG/HDL ratio (log10.[TG:HDL]) The concentration of ApoB and ApoAI were measured using immunoturbidimetric method. The correlation between these measurements was analyzed with Pearson correlation test. RESULTS: The blood samples of 76 subjects were collected and analyzed. The subjects were dominated by male (n=67, 88%) and those whose age ≥55 years old (n=54, 71%). The mean ApoB value was 88.66 mg/dL and ApoAI was 97.39 mg/dL. The AIP value was 0.05. The Pearson correlation test between AIP and ApoB/ApoAI ratio showed a significant positive correlation with the strength of correlation was moderate (r=0.51, p-value<0.01). CONCLUSION: There was a significantly positive and moderate correlation between AIP value and ApoB/ApoAI ratio in acute myocardial infarction patients. KEYWORDS: atherogenic index of plasma, acute myocardial infarction, apolipoprotein B/apolipoprotein A-I rati

NKX2-5 variants screening in patients with atrial septal defect in Indonesia

Background: NKX2-5 variant in atrial septal defect patients has been reported. However, it is not yet been described in the Southeast Asian population. Here, we screened the NKX2-5 variants in patients with atrial septal defect (ASD) in the Indonesian population. Method: We recruited 97 patients with ASD for genetic screening of the NKX2-5 variant using Sanger sequencing. Results: We identified three variants of NKX2-5: NM004387.4:c.63A>G at exon 1, NM004387.4:c.413G>A, and NM004387.4:c.561G>C at exon 2. The first variant is commonly found (85.6) and benign. The last two variants are heterozygous at the same locus. These variants are rare (3.1) and novel. Interestingly, these variants were discovered in familial atrial septal defects with a spectrum of arrhythmia and severe pulmonary hypertension. Conclusion: Our study is the first report of the NKX2-5 variant in ASD patients in the Southeast Asian population, including a novel heterozygous variant: NM004387.4:c.413G>A and NM004387.4:c.561G>C. These variants might contribute to familial ASD risk with arrhythmia and severe pulmonary hypertension. Functional studies are necessary to prove our findings. © 2022, The Author(s)