Publications by authors named "Nghia Huynh"

13 Publications

  • Page 1 of 1

Novel compound heterozygous stop-gain mutations of LRBA in a Vietnamese patient with Common Variable Immune Deficiency.

Mol Genet Genomic Med 2020 05 10;8(5):e1216. Epub 2020 Mar 10.

Functional Genomic Unit, DNA Medical Technology, Ho Chi Minh City, Vietnam.

Background: Lipopolysaccharide-responsive and beige-like anchor (LRBA) deficiency is a rare autosomal recessive common variable immunodeficiency (CVID), affecting 1:25,000-1:50,000 people worldwide. Biallelic mutations in the gene LRBA have been implicated in affected individuals.

Methods: We report a 16-year-old Vietnamese, male patient with recurrent CVID symptoms including chronic diarrhea, interstitial pneumonia, cutaneous granulomatous lesions, hepatosplenomegaly, and finger clubbing. Immunological analyses and whole exome sequencing (WES) were performed to investigate phenotypic and genotypic features.

Results: Immunological analyses revealed hypogammaglobulinemia and low ratios of CD4+/CD8+ T cells. Two novel compound heterozygous stop-gain mutation in LRBA were identified: c.1933C > T (p.R645X) and c.949C > T (p.R317X). Sanger sequencing confirmed the segregation of these variants from the intact parents. The abolished LRBA protein expression was shown by immunoblot analysis. Subsequent treatment potentially saves the child from the same immune thrombocytopenia which led to his brother's untimely death; likely caused by the same LRBA mutations.

Conclusion: This first report of LRBA deficiency in Vietnam expands our knowledge of the diverse phenotypes and genotypes driving CVID. Finally, the utilization of WES shows great promise as an effective diagnostic for CVID in our setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216813PMC
May 2020

Clinical and Hematological Relevance of JAK2V617F, CALR, and MPL Mutations in Vietnamese Patients with Essential Thrombocythemia.

Asian Pac J Cancer Prev 2019 09 1;20(9):2775-2780. Epub 2019 Sep 1.

Department of Hematology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.

Background: The picture of Vietnamese patients with essential thrombocythemia (ET) remains mostly undetermined. Our study intended to determine the frequency of JAK2V617F, CALR exon 9, and MPL exon 10 mutations as well as to analyze clinical characteristics associated with different mutational status in Vietnamese ET patients. Methods: We explored mutations of JAK2V617F, MPL, and CALR from 395 patients using allele specific oligonucleotide – polymerase chain reaction and Sanger sequencing techniques; then, the clinical and hematological features were compared according to mutation patterns. Results: We found that JAK2V617F, CALR exon 9, and MPL exon 10 mutations were present in 56.2%, 27.6%, and 1% of the 395 patients with ET, respectively. Twelve different types of CALR mutation were detected in 109 patients, with the CALR type 1 mutation (c.1099_1150del; L367fs*46) was the most common, followed by CALR type 2 mutation (c.1154_1155insTTGTC; K385fs*47). The JAK2V617F-positive patients had older age, higher white blood cell counts and higher hemoglobin levels but lower platelet counts than patients with CALR mutations or patients negative for triple tests. There was no significant difference regarding sex ratio, white blood cell counts, platelet counts and hemoglobin levels among CALR mutation subtypes. Conclusion: we reported high frequency of JAK2V617F, CALR, and MPL mutations in Vietnamese patients with ET and underscored the importance of combined genetic tests for diagnosis and classification of ET into different subtypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.31557/APJCP.2019.20.9.2775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976857PMC
September 2019

Continuous scavenging of broadband vibrations via omnipotent tandem triboelectric nanogenerators with cascade impact structure.

Sci Rep 2019 Jun 3;9(1):8223. Epub 2019 Jun 3.

Department of Mechanical Engineering, Kyung Hee University, 1732 Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 17104, South Korea.

Ambient vibration energy is highly irregular in force and frequency. Triboelectric nanogenerators (TENG) can convert ambient mechanical energy into useable electricity. In order to effectively convert irregular ambient vibrations into electricity, the TENG should be capable of reliably continuous operation despite variability in input forces and frequencies. In this study, we propose a tandem triboelectric nanogenerator with cascade impact structure (CIT-TENG) for continuously scavenging input vibrations with broadband frequencies. Based on resonance theory, four TENGs were explicitly designed to operate in tandem and cover a targeted frequency range of 0-40 Hz. However, due to the cascade impact structure of CIT-TENG, each TENG could produce output even under non-resonant conditions. We systematically studied the cascade impact dynamics of the CIT-TENG using finite element simulations and experiments to show how it enables continuous scavenging from 0-40 Hz even under low input accelerations of 0.2 G-0.5 G m/s. Finally, we demonstrated that the CIT-TENG could not only scavenge broadband vibrations from a single source such as a car dashboard, but it could also scavenge very low frequency vibrations from water waves and very high frequency vibrations from air compressor machines. Thus, we showed that the CIT-TENG can be used in multiple applications without any need for redesign validating its use as an omnipotent vibration energy scavenger.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-44683-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547642PMC
June 2019

Effects of Embedded TiO Nanoparticles on Triboelectric Nanogenerator Performance.

Micromachines (Basel) 2018 Aug 17;9(8). Epub 2018 Aug 17.

Department of Mechanical Engineering, Kyung Hee University, 1732 Deogyeong-daero, Giheung-gu, Yongin-Si, Gyeonggi-do 446-701, Korea.

Triboelectric nanogenerators (TENGs) are used as self-power sources for various types of devices by converting external waves, wind, or other mechanical energies into electric power. However, obtaining a high-output performance is still of major concern for many applications. In this study, to enhance the output performance of polydimethylsiloxane (PDMS)-based TENGs, highly dielectric TiO nanoparticles (NPs) were embedded as a function of weight ratio. TiO NPs embedded in PDMS at 5% showed the highest output voltage and current. The improved output performance at 5% is strongly related to the change of oxygen vacancies on the PDMS surface, as well as the increased dielectric constant. Specifically, oxygen vacancies in the oxide nanoparticles are electrically positive charges, which is an important factor that can contribute to the exchange and trapping of electrons when driving a TENG. However, in TiO NPs containing over 5%, the output performance was significantly degraded because of the increased leakage characteristics of the PDMS layer due to TiO NPs aggregation, which formed an electron path.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/mi9080407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187469PMC
August 2018

Biomechanical Effects of Bonding Pericervical Dentin in Maxillary Premolars.

J Endod 2018 Apr 16;44(4):659-664. Epub 2018 Feb 16.

University of Toronto, Toronto, Canada. Electronic address:

Introduction: Pericervical dentin (PCD) loss may increase root fracture propensity in root-filled teeth. This study evaluated the impacts of bonding PCD with composite resin (CR) on radicular microstrain distribution and load at failure of root-filled maxillary premolars.

Methods: Ten single-canal maxillary premolars decoronated 2 mm coronal to the cementoenamel junction (CEJ) had canals enlarged with ProTaper Universal instruments (Dentsply Tulsa Dental Specialties, Tulsa, OK) to F3. They were root filled with gutta-percha (GP) to the CEJ and restored with Cavit (3M Deutschland GmbH, Neuss, Germany) (GP group, n = 5) or 6 mm apical to the CEJ and restored with bonded CR to simulate bonding of PCD (bonded PCD group, n = 5). Digital moiré interferometry was used to evaluate pre- and postoperative whole-field microstrain distribution in the root dentin under physiologically relevant loads (10-50 N). Another 30 premolars, similarly treated as groups 1 and 2 or left untreated as controls (n = 10/group), were subjected to cyclic loads (1.2 million cycles, 45 N, 4 Hz) followed by uniaxial compressive load to failure. Mechanical data were analyzed with 1-way analysis of variance and the post hoc Tukey test at a 5% level of significance.

Results: Microstrain distribution showed bending and compressive patterns at the coronal and apical root dentin, respectively. In the GP group, microstrain distribution was unaltered. In the bonded-PCD group, different microstrain distribution suggested stiffening at the PCD. The load at failure did not differ significantly for the GP, bonded PCD, and control groups (P > .05).

Conclusions: CR bonding of PCD might impact the biomechanical responses in maxillary premolar roots at low-level continuous loads. The effect of this impact on root fracture loads when subjected to cyclic load warrants further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joen.2018.01.002DOI Listing
April 2018

Mineral and Bone Disorder in Chronic Kidney Disease: A Case Report from Vietnam.

Blood Purif 2017 5;44 Suppl 1:46-51. Epub 2017 Sep 5.

Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam.

We report a case of calcium pyrophosphate dihydrate deposition disease (CPDD) involving a patient on maintenance hemodialysis (MHD). The 32-year-old man presented in August 2016 with a complaint of left shoulder swelling of 8 months' duration with no trauma or fever. He was diagnosed with nephrotic syndrome in 1998, which progressed to ESRD. He commenced MHD in 2012. Examination at our hospital revealed a soft nontender swelling of the left shoulder. Blood biochemistry showed elevated serum urate, phosphate, β2 microglobulin, and parathyroid hormone. Imaging revealed joint effusion and dense heterogenous deposition. Aspirate analysis showed urate crystals 3+, and culture yielded no growth. Following rheumatology review, the working diagnosis was periarticular tissue tuberculosis, after excluding pseudogout and amyloidosis. Following 1 month of colchicine and allopurinol, synovial fluid microscopy showed CPDD crystals. Symptoms gradually resolved over the course of 6 months. In this rare case, a diagnosis of CPDD was made with a multidisciplinary approach that included imaging and biochemical investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000479619DOI Listing
July 2018

Comparison of the Treatment Efficiency of Bone Marrow-Derived Mesenchymal Stem Cell Transplantation via Tail and Portal Veins in CCl4-Induced Mouse Liver Fibrosis.

Stem Cells Int 2016 29;2016:5720413. Epub 2015 Dec 29.

Laboratory of Stem cell Research and Application, University of Science, VNU-HCM, Ho Chi Minh City 700000, Vietnam; Biology Faculty, University of Science, VNU-HCM, Ho Chi Minh City 700000, Vietnam.

Because of self-renewal, strong proliferation in vitro, abundant sources for isolation, and a high differentiation capacity, mesenchymal stem cells are suggested to be potentially therapeutic for liver fibrosis/cirrhosis. In this study, we evaluated the treatment effects of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) on mouse liver cirrhosis induced by carbon tetrachloride. Portal and tail vein transplantations were examined to evaluate the effects of different injection routes on the liver cirrhosis model at 21 days after transplantation. BM-MSCs transplantation reduced aspartate aminotransferase/alanine aminotransferase levels at 21 days after injection. Furthermore, BM-MSCs induced positive changes in serum bilirubin and albumin and downregulated expression of integrins (600- to 7000-fold), transforming growth factor, and procollagen-α1 compared with the control group. Interestingly, both injection routes ameliorated inflammation and liver cirrhosis scores. All mice in treatment groups had reduced inflammation scores and no cirrhosis. In conclusion, transplantation of BM-MSCs via tail or portal veins ameliorates liver cirrhosis in mice. Notably, there were no differences in treatment effects between tail and portal vein administrations. In consideration of safety, we suggest transfusion of bone marrow-derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/5720413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709782PMC
February 2016

A comparison of the chemical and liver extract-induced hepatic differentiation of adipose derived stem cells.

In Vitro Cell Dev Biol Anim 2015 Nov 15;51(10):1085-92. Epub 2015 Aug 15.

Laboratory of Stem Cell Research and Application, University of Science, VNU-HCM, HCM City, Vietnam.

Adipose-derived stem cells (ADSCs) have been put forward as promising therapeutics for end-stage liver disease (ESLD). In the present study, we compared the effects of defined chemicals and liver extract on the hepatic differentiation of ADSCs. ADSCs were isolated according to the method described in our previously published study. Subsequently, the differentiation of ADSCs was induced separately by chemicals (including hepatic growth factor (HGF), fibroblast growth factor (FGF), and oncostatin M (OSM)) and liver extract (30 μg/ml) in a total period of 21 d. The efficiency of hepatic differentiation was evaluated by changes in the cell morphology, gene expression, and cellular function. The results showed that the liver extract promoted the hepatic differentiation of ADSCs to a significantly greater extent than the chemicals. In the group of ADSCs treated with liver extract, changes in the cell morphology began sooner, and the expression of alpha-FP and albumin genes was higher than that in the chemically treated group. The ADSCs in both the groups stained positive for anti-alpha trypsin (AAT) and albumin markers. The cells also exhibited glycogen storage capacity. Therefore, we concluded that the liver extract could efficiently induce the differentiation of ADSCs into hepatocyte-like cells. This study reveals the potential of mesenchymal stem cell differentiation in the liver extract, which supports further preclinical and clinical research on the application of ADSCs in ESLD treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11626-015-9939-2DOI Listing
November 2015

Comparative pharmacogenetic analysis of risk polymorphisms in Caucasian and Vietnamese children with acute lymphoblastic leukemia: prediction of therapeutic outcome?

Br J Clin Pharmacol 2015 Mar;79(3):429-40

Centre de Technologies Moléculaires Appliquées (CTMA), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL), Brussels, Belgium; Service d'hématologie et oncologie pédiatrique, Cliniques universitaires Saint-Luc, Université catholique de Louvain (UCL), Brussels, Belgium; Pham Ngoc Thach University of Medecin, Ho Chi Minh city, Vietnam; Blood Transfusion and Hematology Hospital, Ho Chi Minh city, Vietnam.

Aims: Acute lymphoblastic leukemia (ALL) is the most common of all paediatric cancers. Aside from predisposing to ALL, polymorphisms could also be associated with poor outcome. Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and/or thiopurine metabolic pathways, i.e. cyclin D1 (CCND1-G870A), γ-glutamyl hydrolase (GGH-C452T), methylenetetrahydrofolate reductase (MTHFR-C677T and MTHFR-A1298C), thymidylate synthase promoter (TYMS-TSER), thiopurine methyltransferase (TPMT*3A and TPMT*3C) and inosine triphosphate pyrophosphatase (ITPA-C94A), in Caucasian (n = 94, age < 20) and Vietnamese (n = 141, age < 16 years) childhood ALL and (b) to assess the impact of a multilocus genetic risk score (MGRS) on relapse-free survival (RFS) using a Cox proportional-hazards regression model.

Results: The prevalence of MTHFR-677TT genotype was significantly higher in Caucasians (P = 0.008), in contrast to the prevalence of TYMS-TSER*3R/3R and ITPA-94AA/AC genotypes which were significantly higher in Vietnamese (P < 0.001 and P = 0.02, respectively). Compared with children with a low MGRS (≤ 3), those with a high MGRS (≥ 4) were 2.06 (95% CI = 1.01, 4.22; P = 0.04) times more likely to relapse. Adding MGRS into a multivariate Cox regression model with race/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC from 0.682 to 0.709 at 24 months).

Conclusion: Including MGRS into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatric ALL. Whether variants on other genes associated with folate metabolism can substantially improve the predictive value of current MGRS is not known but deserves further evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.12481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345953PMC
March 2015

Comparison of long-term outcome between white and Vietnamese children treated for acute lymphoblastic leukemia according to the FRALLE 2000 protocol.

J Pediatr Hematol Oncol 2014 Oct;36(7):534-40

*Department of Pediatric Hematology and Oncology, Cliniques universitaires Saint-Luc †Centre de Technologies Moléculaires Appliquées (CTMA) ∥Epidemiology and Biostatistics Department, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL) ¶Defence Laboratories Department, Belgian Armed Forces, Brussels, Belgium ‡Pham Ngoc Thach University of Medecin §Blood Transfusion and Hematology Hospital, Ho Chi Minh City, Vietnam.

Aim Of This Study: To compare the relapse-free survival (RFS) in Vietnamese (n=141) and white (n=94) children living in Vietnam and Belgium, respectively, and treated in their own country for acute lymphoblastic leukemia according to the same FRALLE 2000 protocol.

Results: RFS was significantly worse in Vietnamese children (hazards ratio=4.48; 95% confidence interval [CI], 2.16-9.3; P<0.01). The 5-year RFS was 83.8% (95% CI, 76.3%-92.0%) and 47.8% (95% CI, 35.6%-64.2%) for white and Vietnamese children, respectively. In the latter group, relapses occurred in bone marrow and cerebrospinal fluid at a much earlier stage. The outcome was compared at first relapse only because of different treatments afterward, according to the country. Both series were similar for sex, age at diagnosis, initial white blood cell count, cytogenetic abnormalities, and corticosensitivity at day 8. Higher frequency of L2-acute lymphoblastic leukemia (P<0.001) but lower frequency of T-acute lymphoblastic leukemia (P=0.004) were observed in Vietnamese children.

Conclusions: Several factors may contribute to the poor RFS in Vietnamese children, which include the time interval before the first intrathecal therapy and differences in the management of drug-related toxicity. However, additional contribution of socioeconomic factors and/or variations in pharmacogenetic polymorphisms in Vietnamese patients cannot currently be ruled out.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPH.0000000000000062DOI Listing
October 2014

Unique secondary chromosomal abnormalities are frequently found in the chronic phase of chronic myeloid leukemia in southern Vietnam.

Cancer Genet Cytogenet 2006 Jul;168(1):59-68

Division of Ultrafine Structure, Department of Pathology, Research Institute of International Medical Center of Japan, Toyama 1-21-1, Shinjuku-ku, Tokyo, 162-0052, Tokyo, Japan.

During the Vietnam War, southern Vietnam was exposed to a large amount of dioxin, a strong human carcinogen. Although we have observed much shorter survival in southern Vietnamese chronic myeloid leukemia (CML) patients, the cause remains to be clarified. Here, we report cytogenetic and molecular findings for 47 CML patients. Cytogenetically, the Philadelphia (Ph) chromosome was found in 44 patients (93.6%); of the remaining 3 patients with Ph-negative CML, 2 exhibited BCR/ABL transcripts but no BCR/ABL FISH fusion signals, suggesting the existence of two clones, with and without the BCR/ABL fusion gene. Surprisingly, in 17 patients (36.2%) (4 at diagnosis, 11 during chronic phase, and 2 in accelerated phase), we found several unique secondary chromosome abnormalities including trisomy 13, partial trisomy 13, and abnormalities of 1p, 3p, 6p, 7p, 10p, and 11p, which are different from the so-called additional chromosome abnormalities (extra Ph, +8, i(17q), +19, and +21) observed in blastic phase CML. FISH analysis revealed the Ph translocation with der(9) deletion in 11 patients (23.4%). Of these, 2 had two clones, with and without der(9) deletion, suggesting that der(9) deletion would occur in a subset of patients during disease progression. These observations point to preexisting genetic instability that induces various secondary chromosome abnormalities and multiple clones, resulting in shorter survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cancergencyto.2005.12.010DOI Listing
July 2006

Coexistence of Philadelphia chromosome positive cells with and without der(9) deletion in a patient with chronic myelogenous leukemia.

Cancer Genet Cytogenet 2006 Jan;164(2):122-7

Division of Ultrafine Structure, Department of Pathology, Research Institute of International Medical Center of Japan, Toyama 1-21-1, Shinjuku-ku, Tokyo 162-0052, Japan.

Recently, large deletions adjacent to the Philadelphia (Ph) translocation breakpoint on the derivative chromosome 9 have been reported to be found in a substantial number of patients with chronic myelogenous leukemia (CML). The existence of der(9) deletion is reported as a powerful indicator of a poor prognosis. So far, der(9) deletion is considered to be generated when the Ph translocation occurs, because when der(9) deletion is found, it is detected in all the Ph-positive (Ph+) cells of a particular CML patient. On FISH examination of 47 Vietnamese CML patients, we found 11 patients carrying der(9) deletion. Among these, two patients harbored Ph+ metaphase cells with der(9) deletion and also Ph+ cells without it. In CML patients with der(9) deletion, reportedly no ABL/BCR transcript is detected. In these two patients, the proportion of Ph+ cells without der(9) deletion was much smaller than that of the cells with der(9) deletion. Nevertheless, we detected a ABL/BCR (1b-b4) transcript in the two patients. This is further evidence for the existence of Ph+ cells without der(9) deletion. It is possible that in some CML patients, der(9) deletion is generated in the progression of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cancergencyto.2005.07.012DOI Listing
January 2006

Anti-atherogenic effect of insulin in vivo.

J Vasc Res 2005 Nov-Dec;42(6):455-62. Epub 2005 Sep 6.

Department of Physiology, University of Toronto, Toronto, Canada.

Metabolic syndrome is a risk factor for atherosclerosis and restenosis. In metabolic syndrome, insulin resistance coexists with hyperinsulinemia and hyperlipidemia. Hyperlipidemia has growth-promoting effects, whereas insulin has both growth-promoting and growth-inhibitory effects on vascular smooth muscle cells in vitro. The objective of this study was to investigate the effects of hyperlipidemia and hyperinsulinemia on vascular cell growth in vivo after arterial injury. Rats fed a low-fat diet were treated with either subcutaneous blank (LFC) or insulin (LFI) implants. Rats fed a high-fat diet also received blank (HFC) or insulin (HFI) implants. After 3 days, rats received balloon carotid injury, and 14 days later they were sacrificed to measure neointimal area and proliferation. Hyperinsulinemia was present in LFI and HFI and hyperlipidemia was present in HFC and HFI. Neointimal area was higher in HFC (0.153 +/- 0.009 mm(2), p < 0.05) but lower in LFI (0.098 +/- 0.005, p < 0.01) than LFC (0.127 +/- 0.005). In HFI (0.142 +/- 0.008, p < 0.05) neointimal area was not different from HFC or LFC. In conclusion, insulin reduced neointimal growth, but the effect of insulin was diminished by the high-fat diet. Thus, our results demonstrate an anti-atherogenic effect of insulin in vivo and suggest that in metabolic syndrome insulin resistance rather than hyperinsulinemia is the atherogenic risk factor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000088099DOI Listing
December 2005