Pub Date : 2019-11-01DOI: 10.4103/0976-9668.275607
Hariyono Winarto
It can not be prevented that we are now somewhere in the starting era of Precision Medicine. We are still adapting and trying to apply for precision medicine in every aspect of human health in our country, Indonesia. Thus, “Precision Medicine: Leading Medical Research to Change Life Results” was chosen as the theme of the 3rd International Conference and Exhibition on Indonesian Medical Education and Research Institute (3rd ICE on IMERI). The conference was held in Jakarta, Indonesia, from 4th to 6th November 2018. Numerous topics of the 3rd ICE on IMERI, covering (1) Drug Development, (2) Sport and Exercise Studies, (3) Metabolic, cardiovascular and aging, (4) Human Nutrition, (5) Human Reproductive, fertility and family planning, (6) Human Genetic, (7) Cancer, (8) Infectious Disease and Immunology, (9) Neuroscience and Brain Development, (10) Occupational and Environment Health, (11) Stem cell, (12) Medical Technology, (13) Hypoxia and Oxidative Stress Study, (14) Hydration, (15) Clinical Research, (16) Molecular Biology, (17) Animal Research, (18) Bioinformatics, and (19) Medical Education.
{"title":"Precision medicine: Leading medical research to change life results","authors":"Hariyono Winarto","doi":"10.4103/0976-9668.275607","DOIUrl":"https://doi.org/10.4103/0976-9668.275607","url":null,"abstract":"It can not be prevented that we are now somewhere in the starting era of Precision Medicine. We are still adapting and trying to apply for precision medicine in every aspect of human health in our country, Indonesia. Thus, “Precision Medicine: Leading Medical Research to Change Life Results” was chosen as the theme of the 3rd International Conference and Exhibition on Indonesian Medical Education and Research Institute (3rd ICE on IMERI). The conference was held in Jakarta, Indonesia, from 4th to 6th November 2018. Numerous topics of the 3rd ICE on IMERI, covering (1) Drug Development, (2) Sport and Exercise Studies, (3) Metabolic, cardiovascular and aging, (4) Human Nutrition, (5) Human Reproductive, fertility and family planning, (6) Human Genetic, (7) Cancer, (8) Infectious Disease and Immunology, (9) Neuroscience and Brain Development, (10) Occupational and Environment Health, (11) Stem cell, (12) Medical Technology, (13) Hypoxia and Oxidative Stress Study, (14) Hydration, (15) Clinical Research, (16) Molecular Biology, (17) Animal Research, (18) Bioinformatics, and (19) Medical Education.","PeriodicalId":16373,"journal":{"name":"Journal of Natural Science, Biology, and Medicine","volume":"18 1","pages":"1 - 1"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83822038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-01DOI: 10.4103/jnsbm.JNSBM_44_19
Anggia Kusno Putri, R. Priambodo, Y. Ariani, S. Arianto, D. Sjarif
Objective: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a rare, recessive, X-linked lysosomal storage disorder caused by a deficiency of lysosomal enzyme iduronate-2-sulfatase (IDS), encoded by IDS gene. I2S plays an important role in the lysosomal degradation of dermatan sulfate and heparan sulfate, with I2S deficiency leading to the accumulation of these glycosaminoglycans in the tissues. Materials and Methods: Exon-specific analyses of IDS exon 8 from eight Indonesian patients with MPS II from Cipto Mangunkusumo Hospital, Jakarta, Indonesia, were performed using polymerase chain reaction and sequencing-based methods. Results: Two novel mutations and a deletion variant of exon 8 were identified among the patients. A single-nucleotide deletion variant (c.1023delA), causing a frameshift in the corresponding amino acid sequence (p.Glu341AspfsTer19), was observed in all patients. In addition, a novel missense mutation (c.1033T>C) resulting in a tryptophan to arginine substitution (p.Trp345Arg), along with a single-nucleotide deletion (c.1041delA) resulting in a second frameshift in the amino acid sequence (p.Lys347AsnfsTer13), was also observed in one patient. Conclusion: This study provides the first mutation analysis of exon 8 of IDS and successfully identified mutations within the IDS gene that may be associated with MPS II. These findings will be added to the IDS gene profile database and may help in the diagnosis of MPS II in future.
{"title":"Mutation analysis of exon 8 of the iduronate-2-sulfatase gene in mucopolysaccharidosis type II patients in Indonesia","authors":"Anggia Kusno Putri, R. Priambodo, Y. Ariani, S. Arianto, D. Sjarif","doi":"10.4103/jnsbm.JNSBM_44_19","DOIUrl":"https://doi.org/10.4103/jnsbm.JNSBM_44_19","url":null,"abstract":"Objective: Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a rare, recessive, X-linked lysosomal storage disorder caused by a deficiency of lysosomal enzyme iduronate-2-sulfatase (IDS), encoded by IDS gene. I2S plays an important role in the lysosomal degradation of dermatan sulfate and heparan sulfate, with I2S deficiency leading to the accumulation of these glycosaminoglycans in the tissues. Materials and Methods: Exon-specific analyses of IDS exon 8 from eight Indonesian patients with MPS II from Cipto Mangunkusumo Hospital, Jakarta, Indonesia, were performed using polymerase chain reaction and sequencing-based methods. Results: Two novel mutations and a deletion variant of exon 8 were identified among the patients. A single-nucleotide deletion variant (c.1023delA), causing a frameshift in the corresponding amino acid sequence (p.Glu341AspfsTer19), was observed in all patients. In addition, a novel missense mutation (c.1033T>C) resulting in a tryptophan to arginine substitution (p.Trp345Arg), along with a single-nucleotide deletion (c.1041delA) resulting in a second frameshift in the amino acid sequence (p.Lys347AsnfsTer13), was also observed in one patient. Conclusion: This study provides the first mutation analysis of exon 8 of IDS and successfully identified mutations within the IDS gene that may be associated with MPS II. These findings will be added to the IDS gene profile database and may help in the diagnosis of MPS II in future.","PeriodicalId":16373,"journal":{"name":"Journal of Natural Science, Biology, and Medicine","volume":"27 1","pages":"109 - 112"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83352357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-01DOI: 10.4103/jnsbm.JNSBM_46_19
Ramadhan Karsono, A. Perdana, Fahreza Saputra, Yulia Pratiwi, Ayu Sari, A. Abinawanto
Objective: Exon 8 estrogen receptor 1 (ESR1) mutations in the ligand-binding domain play an important role in mechanisms of hormonal therapy resistance in breast cancer. Identification of ESR1 mutations is very important in determining the appropriate steps of therapy. In this study, we evaluate Sanger sequencing technique to detect the ESR1 mutation. Methods: This retrospective study was conducted using 49 advanced breast cancer patients with estrogen receptor positive. Deoxyribonucleic acid (DNA) material was extracted from primary breast tumor samples. Exon 8 ESR1 gene mutation was analyzed by Sanger sequencing method using BigDye Direct Sequencing Kit (Applied Biosystem) with gBlock synthesis gene fragment (Integrated DNA Technologies) D538G as a positive control. Results: The mean age of patients was 46.14 (±9.6) years, and 61.2% were in stage 4. There are no exon 8 ESR1 gene mutations detected in 49 primary tumor samples, whereas the gBlock-positive control showed base substitution in 1613A>G (D538G) indicating the success of sequencing reaction. Conclusion: Sanger sequencing has failed to detect ESR1 mutation in primary tumor breast samples. Other advanced molecular techniques should be performed for diagnosis of primary breast tumors.
目的:雌激素受体1 (ESR1)配体结合域外显子8突变在乳腺癌激素治疗耐药机制中发挥重要作用。鉴定ESR1突变对于确定适当的治疗步骤非常重要。在这项研究中，我们评估了Sanger测序技术检测ESR1突变。方法:对49例雌激素受体阳性的晚期乳腺癌患者进行回顾性研究。从乳腺原发肿瘤样本中提取脱氧核糖核酸(DNA)物质。采用BigDye Direct sequencing Kit (Applied Biosystem)，以gBlock合成基因片段(Integrated DNA Technologies) D538G为阳性对照，采用Sanger测序法分析外显子8 ESR1基因突变。结果:患者平均年龄46.14(±9.6)岁，4期占61.2%。49份原发肿瘤样本未检测到ESR1基因外显子8突变，而gblock阳性对照在1613A>G (D538G)出现碱基置换，表明测序反应成功。结论:Sanger测序未能检测到乳腺原发肿瘤样本中的ESR1突变。其他先进的分子技术应用于原发性乳腺肿瘤的诊断。
{"title":"Evaluation of sanger sequencing method for ESR1 mutation detection in primary breast tumor","authors":"Ramadhan Karsono, A. Perdana, Fahreza Saputra, Yulia Pratiwi, Ayu Sari, A. Abinawanto","doi":"10.4103/jnsbm.JNSBM_46_19","DOIUrl":"https://doi.org/10.4103/jnsbm.JNSBM_46_19","url":null,"abstract":"Objective: Exon 8 estrogen receptor 1 (ESR1) mutations in the ligand-binding domain play an important role in mechanisms of hormonal therapy resistance in breast cancer. Identification of ESR1 mutations is very important in determining the appropriate steps of therapy. In this study, we evaluate Sanger sequencing technique to detect the ESR1 mutation. Methods: This retrospective study was conducted using 49 advanced breast cancer patients with estrogen receptor positive. Deoxyribonucleic acid (DNA) material was extracted from primary breast tumor samples. Exon 8 ESR1 gene mutation was analyzed by Sanger sequencing method using BigDye Direct Sequencing Kit (Applied Biosystem) with gBlock synthesis gene fragment (Integrated DNA Technologies) D538G as a positive control. Results: The mean age of patients was 46.14 (±9.6) years, and 61.2% were in stage 4. There are no exon 8 ESR1 gene mutations detected in 49 primary tumor samples, whereas the gBlock-positive control showed base substitution in 1613A>G (D538G) indicating the success of sequencing reaction. Conclusion: Sanger sequencing has failed to detect ESR1 mutation in primary tumor breast samples. Other advanced molecular techniques should be performed for diagnosis of primary breast tumors.","PeriodicalId":16373,"journal":{"name":"Journal of Natural Science, Biology, and Medicine","volume":"28 1","pages":"131 - 135"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90526376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-01DOI: 10.4103/jnsbm.JNSBM_51_19
N. Muna, B. Wiweko, P. Iffanolida, O. Riayati, K. Mutia, R. Febri, E. Mansur, T. Yuningsih, A. Hestiantoro
Objective: Selecting embryos is an important step in the in vitro fertilization process before transferring them to the uterus. There are some invasive methods for choosing a good quality embryo, such as embryo grading. This method evaluates the equality and fragmentation of an embryo. However, this method does not adequately evaluate the chromosomal status of the embryos, which is often necessary for high-risk embryos. Here, we evaluated embryo fragmentation and chromosomal numbers using next-generation sequencing. Materials and Methods: Each embryo was biopsied on the 3rd or 5th culture day to obtain a single blastomere cell. DNA was then extracted from each blastomere and whole-genome amplification was carried out. Amplification products were then sequenced to obtain a ploidy number. Results: Among the 30 embryos that were evaluated, 19 embryos had no fragments, 10 embryos had small fragments, and 1 embryo had moderate fragments. However, 12 of 19 embryos, 57.9% with no fragments were detected to have chromosomal abnormality. Aneuploidy was increased in 7 of 10 embryos (70%) with mild fragments. One moderately fragmented embryo included was surprisingly found to have normal ploidy (100%). Gamma correlation test showed that there was no correlation between fragmentation and the incidence rate of aneuploidy (P > 0.05). Although there was no correlation, the study's result exemplifies that aneuploidy rate increased along with higher fragmentation. Conclusion: This research concluded that embryo fragmentation was not correlated with aneuploidy.
{"title":"Embryo fragmentation and its relationship with aneuploidy","authors":"N. Muna, B. Wiweko, P. Iffanolida, O. Riayati, K. Mutia, R. Febri, E. Mansur, T. Yuningsih, A. Hestiantoro","doi":"10.4103/jnsbm.JNSBM_51_19","DOIUrl":"https://doi.org/10.4103/jnsbm.JNSBM_51_19","url":null,"abstract":"Objective: Selecting embryos is an important step in the in vitro fertilization process before transferring them to the uterus. There are some invasive methods for choosing a good quality embryo, such as embryo grading. This method evaluates the equality and fragmentation of an embryo. However, this method does not adequately evaluate the chromosomal status of the embryos, which is often necessary for high-risk embryos. Here, we evaluated embryo fragmentation and chromosomal numbers using next-generation sequencing. Materials and Methods: Each embryo was biopsied on the 3rd or 5th culture day to obtain a single blastomere cell. DNA was then extracted from each blastomere and whole-genome amplification was carried out. Amplification products were then sequenced to obtain a ploidy number. Results: Among the 30 embryos that were evaluated, 19 embryos had no fragments, 10 embryos had small fragments, and 1 embryo had moderate fragments. However, 12 of 19 embryos, 57.9% with no fragments were detected to have chromosomal abnormality. Aneuploidy was increased in 7 of 10 embryos (70%) with mild fragments. One moderately fragmented embryo included was surprisingly found to have normal ploidy (100%). Gamma correlation test showed that there was no correlation between fragmentation and the incidence rate of aneuploidy (P > 0.05). Although there was no correlation, the study's result exemplifies that aneuploidy rate increased along with higher fragmentation. Conclusion: This research concluded that embryo fragmentation was not correlated with aneuploidy.","PeriodicalId":16373,"journal":{"name":"Journal of Natural Science, Biology, and Medicine","volume":"10 1","pages":"154 - 157"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85455726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-01DOI: 10.4103/jnsbm.JNSBM_32_19
S. Yuliani, Aulia Rizka, C. Pitoyo, M. Muhadi
Objective: Various studies have documented the cases of failure to thrive among elderly patients following admission to the emergency department (ED), leading to early mortality. However, studies determining the predictors of 3-month mortality in elderly patients visiting the ED in Indonesia are lacking. Materials and Methods: A retrospective cohort study was performed using secondary data of elderly patients in the ED at Dr. Cipto Mangunkusumo National Hospital between September 2016 and January 2017. We gathered 3-month mortality data using medical records and telephone interviews. Functional status decline, cognitive function impairment, polypharmacy, delirium, frailty, hypoalbuminemia, malnutrition risk, and Rapid Emergency Medicine Score were analyzed using the Chi-square test. Multivariate logistic regression analysis was performed to identify independent predictors of mortality. Results: From the 501 patients studied, 36 (7.2%) were lost to follow-up. A total of 465 patients were evaluated, with a median age of 67 years old (60–89). The overall 3-month mortality of elderly patients admitted to the ED was 32.5%. The independent predictors of 3-month mortality obtained from the multivariate analysis were functional status decline (odds ratio [OR]: 3.05; 95% confidence interval [CI]: 1.63–5.73), polypharmacy (OR: 2.65; 95% CI: 1.74–4.04), delirium (OR: 2.01; 95% CI: 1.26–3.21), and hypoalbuminemia (OR: 1.89; 95% CI: 1.02–3.50). Conclusion: Functional status decline, polypharmacy, delirium, and hypoalbuminemia are independent predictors of 3-month mortality among elderly patients in the ED.
{"title":"Predictors of 3-month mortality in elderly patients visiting the emergency department: A retrospective cohort study","authors":"S. Yuliani, Aulia Rizka, C. Pitoyo, M. Muhadi","doi":"10.4103/jnsbm.JNSBM_32_19","DOIUrl":"https://doi.org/10.4103/jnsbm.JNSBM_32_19","url":null,"abstract":"Objective: Various studies have documented the cases of failure to thrive among elderly patients following admission to the emergency department (ED), leading to early mortality. However, studies determining the predictors of 3-month mortality in elderly patients visiting the ED in Indonesia are lacking. Materials and Methods: A retrospective cohort study was performed using secondary data of elderly patients in the ED at Dr. Cipto Mangunkusumo National Hospital between September 2016 and January 2017. We gathered 3-month mortality data using medical records and telephone interviews. Functional status decline, cognitive function impairment, polypharmacy, delirium, frailty, hypoalbuminemia, malnutrition risk, and Rapid Emergency Medicine Score were analyzed using the Chi-square test. Multivariate logistic regression analysis was performed to identify independent predictors of mortality. Results: From the 501 patients studied, 36 (7.2%) were lost to follow-up. A total of 465 patients were evaluated, with a median age of 67 years old (60–89). The overall 3-month mortality of elderly patients admitted to the ED was 32.5%. The independent predictors of 3-month mortality obtained from the multivariate analysis were functional status decline (odds ratio [OR]: 3.05; 95% confidence interval [CI]: 1.63–5.73), polypharmacy (OR: 2.65; 95% CI: 1.74–4.04), delirium (OR: 2.01; 95% CI: 1.26–3.21), and hypoalbuminemia (OR: 1.89; 95% CI: 1.02–3.50). Conclusion: Functional status decline, polypharmacy, delirium, and hypoalbuminemia are independent predictors of 3-month mortality among elderly patients in the ED.","PeriodicalId":16373,"journal":{"name":"Journal of Natural Science, Biology, and Medicine","volume":"1 1","pages":"48 - 52"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89660042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-01DOI: 10.4103/jnsbm.JNSBM_28_19
R. Soenarto, Aditya Arbi
Introduction: Brain's decreased oxygen delivery is proposed as a risk factor for postoperative cognitive dysfunction (POCD). This study's objective was to investigate the effect of arterial oxygen content (CaO2) on POCD in patients undergoing open-heart surgery. Subjects and Methods: Adult patients listed for elective open-heart surgery at Cipto Mangunkusumo General Hospital were enrolled. The patients' cognitive function was tested using the Rey Auditory Verbal Learning Test, trail-making test, and digit span test (forward–backward) before and 5 days after surgery. The hemoglobin level, arterial saturation (SaO2), and arterial oxygen partial pressure (PaO2) were measured at the following five time points: before induction, 10 min after the commencement of cardiopulmonary bypass (CPB), 10 min after the cessation of CPB, 6 h postoperatively, and 1 day postoperatively. The CaO2 was calculated as follows: CaO2= 1.36 × hemoglobin × SaO2 + 0.003 × PaO2. Data were compared using Student's t-test or the Mann–Whitney test with SPSS software version 20.0 (IBM Corp., Armonk, NY, USA). Results: POCD was found in nine patients (47.4%). The CaO was significantly lower in patients with POCD than those without POCD at 10 min after the cessation of CPB (12.1 ± 2.6 vs. 14.5 ± 1.7, respectively; P = 0.03). The hemoglobin level appeared to be the cause of the decreased CaO2 in the POCD group (8.5 ± 2.3 vs. 10.2 ± 1.2, P = 0.06). Decreased oxygen content after CPB cessation may impair brain tissue oxygenation that causes POCD. Conclusion: Hemoglobin level may play an important role in POCD development after open-heart surgery.
{"title":"Effect of oxygen content on postoperative cognitive dysfunction in patients undergoing open-heart surgery","authors":"R. Soenarto, Aditya Arbi","doi":"10.4103/jnsbm.JNSBM_28_19","DOIUrl":"https://doi.org/10.4103/jnsbm.JNSBM_28_19","url":null,"abstract":"Introduction: Brain's decreased oxygen delivery is proposed as a risk factor for postoperative cognitive dysfunction (POCD). This study's objective was to investigate the effect of arterial oxygen content (CaO2) on POCD in patients undergoing open-heart surgery. Subjects and Methods: Adult patients listed for elective open-heart surgery at Cipto Mangunkusumo General Hospital were enrolled. The patients' cognitive function was tested using the Rey Auditory Verbal Learning Test, trail-making test, and digit span test (forward–backward) before and 5 days after surgery. The hemoglobin level, arterial saturation (SaO2), and arterial oxygen partial pressure (PaO2) were measured at the following five time points: before induction, 10 min after the commencement of cardiopulmonary bypass (CPB), 10 min after the cessation of CPB, 6 h postoperatively, and 1 day postoperatively. The CaO2 was calculated as follows: CaO2= 1.36 × hemoglobin × SaO2 + 0.003 × PaO2. Data were compared using Student's t-test or the Mann–Whitney test with SPSS software version 20.0 (IBM Corp., Armonk, NY, USA). Results: POCD was found in nine patients (47.4%). The CaO was significantly lower in patients with POCD than those without POCD at 10 min after the cessation of CPB (12.1 ± 2.6 vs. 14.5 ± 1.7, respectively; P = 0.03). The hemoglobin level appeared to be the cause of the decreased CaO2 in the POCD group (8.5 ± 2.3 vs. 10.2 ± 1.2, P = 0.06). Decreased oxygen content after CPB cessation may impair brain tissue oxygenation that causes POCD. Conclusion: Hemoglobin level may play an important role in POCD development after open-heart surgery.","PeriodicalId":16373,"journal":{"name":"Journal of Natural Science, Biology, and Medicine","volume":"166 1","pages":"7 - 10"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76873264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-01DOI: 10.4103/jnsbm.JNSBM_38_19
R. Aji, R. Priambodo, C. Hafifah, D. Sjarif
Objective: Gaucher disease (GD) is the most common lysosomal storage disorder. It is caused by a deficiency of β-glucocerebrosidase (GCase, encoded by GBA) and its inheritance is autosomal recessive. Analyses of common mutations in GBA have been performed in China, Singapore, Taiwan, and Thailand, but not previously in Indonesia. The objective of this study was to identify a common exonic mutation in exons 9–11 of GBA in GD patients in Indonesia. Materials and Methods: Genetic analysis was performed using blood samples from two GD patients and thirty non-GD patients. Peripheral leukocyte samples were collected at the Dr. Cipto Mangunkusumo Referral Hospital, Jakarta, Indonesia. The polymerase chain reaction was performed to amplify exons 9–11 of the GBA gene using specific primers, then the product was digested with Nci I restriction enzyme, and the sequence confirmed by sequence analysis. Results: This identified an L444P mutation located in exon 10. This missense mutation changes amino acid 483 of GCase from leucine to proline and is categorized as a pathogenic variant. Conclusion: This identification of the L444P mutation adds to a database for determining the prevalence of GD in Indonesia. However, further research is needed to ascertain the impact of the L444P mutation on the structure of GCase and to explore any mutations in the other exons.
{"title":"Screening for exonic mutation L444P in Indonesian patients with gaucher disease using exons 9–11","authors":"R. Aji, R. Priambodo, C. Hafifah, D. Sjarif","doi":"10.4103/jnsbm.JNSBM_38_19","DOIUrl":"https://doi.org/10.4103/jnsbm.JNSBM_38_19","url":null,"abstract":"Objective: Gaucher disease (GD) is the most common lysosomal storage disorder. It is caused by a deficiency of β-glucocerebrosidase (GCase, encoded by GBA) and its inheritance is autosomal recessive. Analyses of common mutations in GBA have been performed in China, Singapore, Taiwan, and Thailand, but not previously in Indonesia. The objective of this study was to identify a common exonic mutation in exons 9–11 of GBA in GD patients in Indonesia. Materials and Methods: Genetic analysis was performed using blood samples from two GD patients and thirty non-GD patients. Peripheral leukocyte samples were collected at the Dr. Cipto Mangunkusumo Referral Hospital, Jakarta, Indonesia. The polymerase chain reaction was performed to amplify exons 9–11 of the GBA gene using specific primers, then the product was digested with Nci I restriction enzyme, and the sequence confirmed by sequence analysis. Results: This identified an L444P mutation located in exon 10. This missense mutation changes amino acid 483 of GCase from leucine to proline and is categorized as a pathogenic variant. Conclusion: This identification of the L444P mutation adds to a database for determining the prevalence of GD in Indonesia. However, further research is needed to ascertain the impact of the L444P mutation on the structure of GCase and to explore any mutations in the other exons.","PeriodicalId":16373,"journal":{"name":"Journal of Natural Science, Biology, and Medicine","volume":"114 1","pages":"59 - 61"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79911996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-01DOI: 10.4103/jnsbm.JNSBM_79_19
R. Aji, I. Lestari, R. Priambodo, C. Hafifah, D. Sjarif
Objective: Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by the accumulation of the glycolipid glucosylceramide encoded by the GBA gene in certain organs. At present, more than 460 GBA intronic mutations have been reported in several subpopulations worldwide, but many have never been reported in Indonesia. Here, we aimed to screen for intronic mutations of GBA that might be present in patients with GD in Indonesia. Materials and Methods: Blood samples from patients with and without GD were obtained from the National Dr. Cipto Mangunkusumo Referral Hospital, Jakarta, Indonesia. Genomic DNA samples from peripheral leukocytes were extracted, purified, and amplified using the polymerase chain reaction (PCR) with specific primers. Products of PCR were visualized by gel electrophoresis and were further sequenced to analyze the presence of mutations in intron (intervening sequence [IVS]) 9 of GBA. Results: A mutant allele was identified at IVS9+141A>G, discovered at nucleotide 9335 in IVS 9. This mutation had been reported in India before and was categorized as nonpathogenic. Conclusion: Our study may be used as supplemental information for the GD database in Indonesia and will also open new research opportunities for predicting splicing processes in other intronic variants among patients with GD in Indonesia.
{"title":"Screening of intronic mutation IVS9+141A>G in an Indonesian patient with Gaucher disease","authors":"R. Aji, I. Lestari, R. Priambodo, C. Hafifah, D. Sjarif","doi":"10.4103/jnsbm.JNSBM_79_19","DOIUrl":"https://doi.org/10.4103/jnsbm.JNSBM_79_19","url":null,"abstract":"Objective: Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by the accumulation of the glycolipid glucosylceramide encoded by the GBA gene in certain organs. At present, more than 460 GBA intronic mutations have been reported in several subpopulations worldwide, but many have never been reported in Indonesia. Here, we aimed to screen for intronic mutations of GBA that might be present in patients with GD in Indonesia. Materials and Methods: Blood samples from patients with and without GD were obtained from the National Dr. Cipto Mangunkusumo Referral Hospital, Jakarta, Indonesia. Genomic DNA samples from peripheral leukocytes were extracted, purified, and amplified using the polymerase chain reaction (PCR) with specific primers. Products of PCR were visualized by gel electrophoresis and were further sequenced to analyze the presence of mutations in intron (intervening sequence [IVS]) 9 of GBA. Results: A mutant allele was identified at IVS9+141A>G, discovered at nucleotide 9335 in IVS 9. This mutation had been reported in India before and was categorized as nonpathogenic. Conclusion: Our study may be used as supplemental information for the GD database in Indonesia and will also open new research opportunities for predicting splicing processes in other intronic variants among patients with GD in Indonesia.","PeriodicalId":16373,"journal":{"name":"Journal of Natural Science, Biology, and Medicine","volume":"30 1","pages":"123 - 125"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77583212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-01DOI: 10.4103/jnsbm.JNSBM_40_19
N. Prakoso, R. Priambodo, Y. Ariani, C. Hafifah, D. Sjarif
Objective: Mucopolysaccharidosis IVA (MPS IVA), or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of galactosamine (N-acetyl)-6-sulfatase (GALNS) enzyme that leads to the accumulation of keratan sulfate and chondroitin-6-sulfate in the lysosome and eventually in the tissue or organ damaged. This enzyme deficiency occurs because of mutations in the galactosamine (N-acetyl)-6-sulfatase (GALNS) gene located at locus 16q24.3. GALNS comprises 14 exons, has a size of ~43 kb, and encodes 522 amino acids. Currently, 47 of 368 mutations have been detected in exon 5, indicating that this region is a hotspot of mutations. The objective of this study was to analyze the mutations in exon 5 of GALNS in MPS IVA patients in Indonesia. Materials and Methods: Genomic DNA was isolated from fresh blood samples obtained from patients with MPS IVA and normal individuals at Cipto Mangunkusumo Hospital. Exon 5 of GALNS was amplified using a pair of specific primers, and polymerase chain reaction products were sequenced using an automated sequencing technique. Results: We found a novel missense mutation c.503G>T that alters the amino acid at position 168 from glycine to valine (G168V). Three previously reported variations identified in this study are c.510T>C (Y170), c.566 + 5T>C, and IVS5 + 134G>A. Conclusion: This finding provides new data about variants in exon 5 of GALNS. Further, research is needed to identify variations in other exons and to map the mutation profile in MPS IVA patients in Indonesia.
{"title":"Identification of a novel variant in exon 5 of galactosamine (N-acetyl)-6-sulfatase gene in mucopolysaccharidosis IVA patients in Indonesia","authors":"N. Prakoso, R. Priambodo, Y. Ariani, C. Hafifah, D. Sjarif","doi":"10.4103/jnsbm.JNSBM_40_19","DOIUrl":"https://doi.org/10.4103/jnsbm.JNSBM_40_19","url":null,"abstract":"Objective: Mucopolysaccharidosis IVA (MPS IVA), or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of galactosamine (N-acetyl)-6-sulfatase (GALNS) enzyme that leads to the accumulation of keratan sulfate and chondroitin-6-sulfate in the lysosome and eventually in the tissue or organ damaged. This enzyme deficiency occurs because of mutations in the galactosamine (N-acetyl)-6-sulfatase (GALNS) gene located at locus 16q24.3. GALNS comprises 14 exons, has a size of ~43 kb, and encodes 522 amino acids. Currently, 47 of 368 mutations have been detected in exon 5, indicating that this region is a hotspot of mutations. The objective of this study was to analyze the mutations in exon 5 of GALNS in MPS IVA patients in Indonesia. Materials and Methods: Genomic DNA was isolated from fresh blood samples obtained from patients with MPS IVA and normal individuals at Cipto Mangunkusumo Hospital. Exon 5 of GALNS was amplified using a pair of specific primers, and polymerase chain reaction products were sequenced using an automated sequencing technique. Results: We found a novel missense mutation c.503G>T that alters the amino acid at position 168 from glycine to valine (G168V). Three previously reported variations identified in this study are c.510T>C (Y170), c.566 + 5T>C, and IVS5 + 134G>A. Conclusion: This finding provides new data about variants in exon 5 of GALNS. Further, research is needed to identify variations in other exons and to map the mutation profile in MPS IVA patients in Indonesia.","PeriodicalId":16373,"journal":{"name":"Journal of Natural Science, Biology, and Medicine","volume":"19 1","pages":"99 - 102"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79410336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-01DOI: 10.4103/jnsbm.JNSBM_69_19
Dewi Irawati Soeria Santoso, Trimar Handayani, Delima Mareta, N. Paramita, S. Jusman, Ermita I. Ibrahim Ilyas
Introduction: Mitochondrial biogenesis is affected by peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and can be induced through physical exercise. Lactate from the skeletal muscle produced in the heart during exercise can be used as an energy source through conversion by lactate dehydrogenase B (LDH B). This study compared the effects of continuous training (CT) and interval training (IT) on PGC-1α and LDH B levels in the adult rat hearts. Materials and Methods: Fifteen male adult Wistar rats (12 months old) were randomly divided into three groups as follows: A control Group (c), a CT group and an IT group. Training was conducted using a rodent treadmill, 5 days/week for 8 weeks. The duration was 50 min for the CT group. In the IT group, training consisted of 4 bouts of 4 min of exercise, followed by rest intervals of 1 min. Speed was increased each week. After 8 weeks of training, the rats were sacrificed, and the levels of PGC-1α and LDH B in heart tissue were measured using enzyme-linked immunosorbent assay. Results: Differences in PGC-1α levels between groups were statistically significant (P = 0.008), while differences in LDH B levels were not statistically significant (P = 0.063). Levels of PGC-1α and LDH B were higher in the CT group than in the IT group. Conclusion: We concluded that CT has a greater effect on energy metabolism in the heart than IT.
{"title":"Effect of interval and continuous training on proliferator-activated receptor gamma coactivator-1α and lactate dehydrogenase B levels in adult rat heart","authors":"Dewi Irawati Soeria Santoso, Trimar Handayani, Delima Mareta, N. Paramita, S. Jusman, Ermita I. Ibrahim Ilyas","doi":"10.4103/jnsbm.JNSBM_69_19","DOIUrl":"https://doi.org/10.4103/jnsbm.JNSBM_69_19","url":null,"abstract":"Introduction: Mitochondrial biogenesis is affected by peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and can be induced through physical exercise. Lactate from the skeletal muscle produced in the heart during exercise can be used as an energy source through conversion by lactate dehydrogenase B (LDH B). This study compared the effects of continuous training (CT) and interval training (IT) on PGC-1α and LDH B levels in the adult rat hearts. Materials and Methods: Fifteen male adult Wistar rats (12 months old) were randomly divided into three groups as follows: A control Group (c), a CT group and an IT group. Training was conducted using a rodent treadmill, 5 days/week for 8 weeks. The duration was 50 min for the CT group. In the IT group, training consisted of 4 bouts of 4 min of exercise, followed by rest intervals of 1 min. Speed was increased each week. After 8 weeks of training, the rats were sacrificed, and the levels of PGC-1α and LDH B in heart tissue were measured using enzyme-linked immunosorbent assay. Results: Differences in PGC-1α levels between groups were statistically significant (P = 0.008), while differences in LDH B levels were not statistically significant (P = 0.063). Levels of PGC-1α and LDH B were higher in the CT group than in the IT group. Conclusion: We concluded that CT has a greater effect on energy metabolism in the heart than IT.","PeriodicalId":16373,"journal":{"name":"Journal of Natural Science, Biology, and Medicine","volume":"41 1","pages":"140 - 143"},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76072377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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