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1.
Polymers (Basel) ; 14(10)2022 May 11.
Article in English | MEDLINE | ID: mdl-35631835

ABSTRACT

Starch-based biodegradable foams with a high starch content are developed using industrial starch as the base material and supercritical CO2 as blowing or foaming agents. The superior cushioning properties of these foams can lead to competitiveness in the market. Despite this, a weak melting strength property of starch is not sufficient to hold the foaming agents within it. Due to the rapid diffusion of foaming gas into the environment, it is difficult for starch to maintain pore structure in starch foams. Therefore, producing starch foam by using supercritical CO2 foaming gas faces severe challenges. To overcome this, we have synthesized thermoplastic starch (TPS) by dispersing starch into water or glycerin. Consecutively, the TPS surface was modified by compatibilizer silane A (SA) to improve the dispersion with poly(butylene adipate-co-terephthalate) (PBAT) to become (TPS with SA)/PBAT composite foam. Furthermore, the foam-forming process was optimized by varying the ratios of TPS and PBAT under different forming temperatures of 85 °C to 105 °C, and two different pressures, 17 Mpa and 23 Mpa were studied in detail. The obtained results indicate that the SA surface modification on TPS can influence the great compatibility with PBAT blended foams (foam density: 0.16 g/cm3); whereas unmodified TPS and PBAT (foam density: 0.349 g/cm3) exhibit high foam density, rigid foam structure, and poor tensile properties. In addition, we have found that the 80% TPS/20% PBAT foam can be achieved with good flexible properties. Because of this flexibility, lightweight and environment-friendly nature, we have the opportunity to resolve the strong demands from the packing market.

2.
Rev. Fac. Med. Hum ; 22(2): 225-227, Abril.- Jun. 2022.
Article in English, Spanish | LILACS-Express | LILACS | ID: biblio-1371478

ABSTRACT

El trasplante de médula ósea, conocido actualmente como trasplante de progenitores hematopoyéticos (TPH), implica la infusión de células progenitoras hematopoyéticas sanas a pacientes con médula ósea disfuncional, disminuida o comprometida por neoplasias hematológicas. Desde su primera exploración en seres humanos en la década de 1950 basados en los resultados obtenidos en modelos animales, en la actualidad, en Europa y países colaboradores se han realizado más de un millón de procedimientos, gracias además a una red internacional de registro de donantes de medula ósea y al avance de la tecnología en cuanto al tratamiento de soporte, la detección temprana de complicaciones y la tipificación de la histocompatibilidad (HLA) con las que se puede seleccionar mejor a los donante potenciales.


Bone marrow transplantation, currently known as hematopoietic stem cell transplant (HSCT), involves the infusion of stem cells healthy hematopoietic cells to patients with dysfunctional bone marrow, diminished or compromised by hematological neoplasms. Since its rst exploration in humans in the 1950s based on the results obtained in animal models, more than one million procedures have now been performed in Europe and collaborating countries. Early detection of complications and histocompatibility typing (HLA) with which potential donors can be better-selected thanks to an international donor registry network of bone marrow and the advancement of technology in terms of support treatment.

3.
Polymers (Basel) ; 15(1)2022 Dec 28.
Article in English | MEDLINE | ID: mdl-36616479

ABSTRACT

Biodegradable foams are a potential substitute for most fossil-fuel-derived polymer foams currently used in the cushion furniture-making industry. Thermoplastic starch (TPS) and poly(butylene adipate-co-terephthalate) (PBAT) are biodegradable polymers, although their poor compatibility does not support the foam-forming process. In this study, we investigated the effect of polyethylene glycol (PEG) with or without silane A (SA) on the foam density, cell structure and tensile properties of TPS/PBAT blends. The challenges in foam forming were explored through various temperature and pressure values under supercritical carbon dioxide (CO2) conditions. The obtained experimental results indicate that PEG and SA act as a plasticizer and compatibilizer, respectively. The 50% (TPS with SA + PEG)/50% PBAT blends generally produce foams that have a lower foam density and better cell structure than those of 50% (TPS with PEG)/50% PBAT blends. The tensile property of each 50% (TPS with SA + PEG)/50% PBAT foam is generally better than that of each 50% (TPS with PEG)/50% PBAT foam.

4.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1367800

ABSTRACT

Introducción: La carmustina es un agente antineoplásico alquilante utilizado en el tratamiento de mielomas, linfomas y otros tipos de cáncer. La cardiotoxicidad por carmustina es una reacción adversa muy rara, por lo que debe ser identificada oportunamente para prevenir desenlaces fatales. Reporte de caso: Se presenta un caso inusual de una paciente con cardiotoxicidad aguda grave reversible posterior a la administración endovenosa de carmustina. Al suspenderla exposición a este producto e iniciar tratamiento sintomatológico, la paciente se recupera satisfactoriamente sin nueva manifestación cardiaca. El caso fue notificado como reacción adversa medicamentosa y al evaluarse la causalidad entre la cardiotoxicidad y la carmustina, resultó probable (puntaje final =7). Conclusiones: El presente caso puede ser considerado una señal en farmacovigilancia, por lo que, los clínicos deben ser conscientes del riesgo potencial de cardiotoxicidad en pacientes expuestos a carmustina. Se recomienda realizar farmacovigilancia activa a los fármacos oncológicos.


Background: Carmustine is an alkylating agent used in the treatment of myeloma, lymphomas and other cancers. Cardiotoxicity due to carmustine is a rare adverse reaction that must be identified early to prevent fatal outcomes. Report case: We present an unusual case of acute cardiac toxicity related to the intravenous administration of carmustine. After stopping the carmustine, patient received symptomatic treatment and, finally was fully recovered. The case was reported as adverse drug reaction and we performed a pharmacovigilance causality assessment between carmustine and cardiotoxicity, resulting in probable (final score = 7). Conclusions: This case might be considered as a signal in pharmacovigilance. Clinicians should be aware of the potential risk of cardiotoxicity in patients exposed to carmustine. It is recommended to implement active pharmacovigilance to chemotherapy.

5.
Transpl Immunol ; 63: 101332, 2020 12.
Article in English | MEDLINE | ID: mdl-32927096

ABSTRACT

INTRODUCTION: Antibody mediated rejection is the leading cause of kidney transplant failure. Not all antibodies are harmful and some may be protective. Immunoglulin Gs, of which there are four subtypes, are detected by single antigen bead testing. The aims of this study were to characterise the IgG subclass profiles for class I HLA-specific antibodies in an uncensored post-transplant population and to determine the underlying relationship between reactivity patterns and MFI cut-offs with the pan-IgG assay. METHODS: Patients were recruited to the study who were transplanted in our centre between 2009 and 2014. Prospectively stored post-transplant serum initially underwent a Labscreen Mixed assay and those positive for class I HLA-specific antibody underwent standard SAB testing, EDTA, 1 in 10 dilution and IgG subclass modifications using the Luminex platform. A total of 4947 bead reactions from 51 patients were analysed. RESULTS: A 1 in 10 dilution was used as a comparator pan-IgG assay for summed subclass and individual subclass linear regression analyses. Using a dilution to standard assay ratio we characterised all reactions for prozone potential i.e. how likely there is to be inhibition related to complement complex formation. We stratified samples into degrees of association and were able to determine suggested MFI thresholds of Log 5.35 for the dilution assay and Log 5.05 for the summed subclass assay when considering a Log MFI of 6.9 (1000) in the standard assay. Using individual subclass dominant reactions (>70%) we were able to determine linear relationships between the 1 in 10 dilution pan-IgG assay and the individual subclass assays (excluding prozone potential reactions for IgG1/3) enabling us to suggest Log MFI thresholds of 5.03, 3.58, 4.3 and 4.05 respectively for IgG1-4. DISCUSSION: We recommend a 1 in 10 dilution as the optimum pan-IgG comparator assay for a subclass analysis. We advocate the utilisation of the summed subclass assay to determine overall relationships and potential subclass failures. Following others, we recommend serum pre-treatment of the subclass assays to mitigate prozone. We suggest cut-offs for each IgG subclass which should be used with caution given the many inhibitory influences which may include competitive inhibition for bead binding, IgM and IgA interference and under-representation of specific subclasses on the bead panel.


Subject(s)
HLA Antigens/immunology , Histocompatibility Antigens Class I/immunology , Immune Sera/chemistry , Immunoglobulin G/analysis , Immunoglobulin Isotypes/analysis , Immunosorbent Techniques , Kidney Transplantation , Complement System Proteins/metabolism , Cross Reactions , Humans , Immune Sera/metabolism , Isoantigens/immunology , Microspheres , Transplant Recipients
6.
Transpl Immunol ; 62: 101310, 2020 10.
Article in English | MEDLINE | ID: mdl-32574596

ABSTRACT

INTRODUCTION: Single antigen bead testing (SAB) for HLA-specific antibody enables efficient organ allocation and aids in the diagnosis of antibody mediated rejection. In this retrospective cohort study, a population of kidney transplant recipients possessing HLA Class I antibodies was used to evaluate the best method for resolving complement interference, the so called "prozone" effect. The aim was to compare the use of EDTA versus a Biotin-Streptavidin Complex as methodological approaches for abating the prozone effect using a fixed 1 in 10 dilution as validation. METHODS: One hundred and seventeen patients transplanted in our centre between 2009 and 2014 were identified as having class I HLA-specific antibody(-ies) using a Labscreen® Mixed assay. Positive sera underwent class I HLA-specific SAB testing; for comparison a standard SAB with and without EDTA, BSC and dilution (1 in 10) modifications were utilised. Samples were processed on the Luminex platform generating 11,349 bead reactions for analysis. RESULTS: We identified sera from 23 patients giving rise to 170 bead reactions showing complement interference. Using linear modelling, we observed slightly higher MFIs on average in both EDTA and BSC modifications when compared to the standard assay, allowing the nominal threshold MFI of 2000 in the standard assay to be adjusted to 2097 and 2033 in the EDTA and BSC assays respectively. We calculated 99% prediction intervals to establish outlier bead reactions for each assay. The 1 in 10 dilution was used as a crosscheck for determining which prozone reactions were overcome by EDTA and BSC. Using ROC curve analysis, EDTA was found to be ~90% sensitive and 100% specific compared to BSC which was ~60% sensitive and 100% specific in ameliorating prozone positive reactions at the thresholds defined by linear models. DISCUSSION: Our data indicates that both EDTA and BSC are suitable assays in overcoming CMI. We recommend that all clinical laboratories adopt a validated assay designed specifically to abrogate CMI for all potential renal transplant recipients, as the standard assay is inhibited in nearly 20% of a post-transplant cohort.


Subject(s)
Bacterial Proteins/metabolism , Biotin/analogs & derivatives , Edetic Acid/metabolism , Epitopes , Graft Rejection/immunology , Histocompatibility Testing/methods , Isoantibodies/blood , Kidney Transplantation , Biotin/metabolism , Cohort Studies , Complement System Proteins/metabolism , Epitopes/immunology , Graft Rejection/diagnosis , HLA Antigens/immunology , Histocompatibility Antigens Class I/immunology , Humans , Predictive Value of Tests , Prognosis , Retrospective Studies
7.
Int J Environ Health Res ; 29(4): 430-440, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30479158

ABSTRACT

Oysters can accumulate potentially pathogenic bacteria, such as Vibrio cholerae, V. parahaemolyticus, and V. vulnificus. The aim of this study was to detect the presence of these Vibrio species and their toxigenic variants in oysters from the Gulf of Mexico sold in Mexico City. Oyster samples were studied using traditional culture and molecular polymerase chain reaction analysis. V. cholerae was present in 30.4% of the samples and its toxigenic variant chxA+ in 26.1%. It was isolated only in deshelled oysters, mainly in the dry season. V. parahaemolyticus was present in 95.7% of the samples and the toxigenic variant was found in 17.4%. V. vulnificus was identified in 60.9% of the samples, 38% of which corresponded to the environmental genotype and 21.7% to the clinical genotype, mainly in the cold season. Consumption of the oysters analyzed poses health risks due to the presence of Vibrio species, especially in deshelled oysters.


Subject(s)
Food Microbiology , Ostreidae/microbiology , Seafood/microbiology , Vibrio/isolation & purification , Animals , Bacterial Toxins/genetics , Bacterial Toxins/metabolism , Colony Count, Microbial , Genotype , Gulf of Mexico , Mexico , Polymerase Chain Reaction , Seasons , Vibrio/genetics
8.
Faraday Discuss ; 202: 61-77, 2017 09 21.
Article in English | MEDLINE | ID: mdl-28671209

ABSTRACT

A family of monomers, including 2,5-hexandiol, 2,7-octandiol, 2,5-furandicarboxylic acid (FDCA), terephthalic acid (TA), and branched-chain adipic and pimelic acid derivatives, all find a common derivation in the biomass-derived platform molecule 5-(chloromethyl)furfural (CMF). The diol monomers, previously little known to polymer chemistry, have been combined with FDCA and TA derivatives to produce a range of novel polyesters. It is shown that the use of secondary diols leads to polymers with higher glass transition temperatures (Tg) than those prepared from their primary diol equivalents. Two methods of polymerisation were investigated, the first employing activation of the aromatic diacids via the corresponding diacid chlorides and the second using a transesterification procedure. Longer chain diols were found to be more reactive than the shorter chain alternatives, generally giving rise to higher molecular weight polymers, an effect shown to be most pronounced when using the transesterification route. Finally, novel diesters with high degrees of branching in their hydrocarbon chains are introduced as potential monomers for possible low surface energy materials applications.


Subject(s)
Adipates/chemistry , Dicarboxylic Acids/chemistry , Furans/chemistry , Glycols/chemistry , Phthalic Acids/chemistry , Pimelic Acids/chemistry , Polyesters/chemistry , Biomass , Molecular Structure , Polyesters/chemical synthesis
9.
PLoS One ; 12(1): e0169722, 2017.
Article in English | MEDLINE | ID: mdl-28099500

ABSTRACT

Vibrio parahaemolyticus is an important human pathogen that has been isolated worldwide from clinical cases, most of which have been associated with seafood consumption. Environmental and clinical toxigenic strains of V. parahaemolyticus that were isolated in Mexico from 1998 to 2012, including those from the only outbreak that has been reported in this country, were characterized genetically to assess the presence of the O3:K6 pandemic clone, and their genetic relationship to strains that are related to the pandemic clonal complex (CC3). Pathogenic tdh+ and tdh+/trh+ strains were analyzed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Also, the entire genome of a Mexican O3:K6 strain was sequenced. Most of the strains were tdh/ORF8-positive and corresponded to the O3:K6 serotype. By PFGE and MLST, there was very close genetic relationship between ORF8/O3:K6 strains, and very high genetic diversities from non-pandemic strains. The genetic relationship is very close among O3:K6 strains that were isolated in Mexico and sequences that were available for strains in the CC3, based on the PubMLST database. The whole-genome sequence of CICESE-170 strain had high similarity with that of the reference RIMD 2210633 strain, and harbored 7 pathogenicity islands, including the 4 that denote O3:K6 pandemic strains. These results indicate that pandemic strains that have been isolated in Mexico show very close genetic relationship among them and with those isolated worldwide.


Subject(s)
Vibrio parahaemolyticus/genetics , Vibrio parahaemolyticus/pathogenicity , Disease Outbreaks , Electrophoresis, Gel, Pulsed-Field , Genome, Bacterial , Genomic Islands , Humans , Mexico/epidemiology , Multilocus Sequence Typing , Vibrio Infections/epidemiology , Vibrio Infections/microbiology , Vibrio parahaemolyticus/isolation & purification
10.
ChemSusChem ; 10(1): 166-170, 2017 Jan 10.
Article in English | MEDLINE | ID: mdl-27873475

ABSTRACT

Electrolysis of biomass-derived carbonyl compounds is an alternative to condensation chemistry for supplying products with chain length >C6 for biofuels and renewable materials production. Kolbe coupling of biomass-derived levulinic acid is used to obtain 2,7-octanedione, a new platform molecule only two low process-intensity steps removed from raw biomass. Hydrogenation to 2,7-octanediol provides a chiral secondary diol largely unknown to polymer chemistry, whereas intramolecular aldol condensation followed by hydrogenation yields branched cycloalkanes suitable for use as high-octane, cellulosic gasoline. Analogous electrolysis of an itaconic acid-derived methylsuccinic monoester yields a chiral 2,5-dimethyladipic acid diester, another underutilized monomer owing to lack of availability.


Subject(s)
Biofuels , Biomass , Levulinic Acids/chemistry , Polymers/chemistry , Aldehydes/chemistry , Catalysis , Cycloparaffins/chemistry , Electrochemistry , Ketones/chemistry , Polyesters/chemistry
11.
Environ Monit Assess ; 188(11): 602, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27709461

ABSTRACT

Oysters can accumulate potentially pathogenic water bacteria. The objective of this study was to compare two procedures to quantify Vibrio species present in oysters to determine the most sensitive method. We analyzed oyster samples from the Gulf of Mexico, commercialized in Mexico City. The samples were inoculated in tubes with alkaline peptone water (APW), based on three tubes and four dilutions (10-1 to 10-4). From these tubes, the first quantification of Vibrio species was performed (most probable number (MPN) from tubes) and bacteria were inoculated by streaking on thiosulfate-citrate-bile salts-sucrose (TCBS) petri dishes. Colonies were isolated for a second quantification (MPN from dishes). Polymerase chain reaction (PCR) was used to determine species with specific primers: ompW for Vibrio cholerae, tlh for Vibrio parahaemolyticus, and VvhA for Vibrio vulnificus. Simultaneously, the sanitary quality of oysters was determined. The quantification of V. parahaemolyticus was significantly higher in APW tubes than in TCBS dishes. Regarding V. vulnificus counts, the differences among both approaches were not significant. In contrast, the MPNs of V. cholerae obtained from dishes were higher than from tubes. The quantification of MPNs through PCR of V. parahaemolyticus and V. vulnificus obtained from APW was sensitive and recommendable for the detection of both species. In contrast, to quantify V. cholerae, it was necessary to isolate colonies on TCBS prior PCR. Culturing in APW at 42 °C could be an alternative to avoid colony isolation. The MPNs of V. cholerae from dishes was associated with the bad sanitary quality of the samples.


Subject(s)
Environmental Monitoring/methods , Ostreidae/microbiology , Shellfish/microbiology , Vibrio cholerae/isolation & purification , Vibrio parahaemolyticus/isolation & purification , Vibrio vulnificus/isolation & purification , Animals , Gulf of Mexico , Mexico , Polymerase Chain Reaction/veterinary , Shellfish/standards , Vibrio cholerae/genetics , Vibrio parahaemolyticus/genetics , Vibrio vulnificus/genetics
12.
Int J Environ Health Res ; 25(6): 614-27, 2015.
Article in English | MEDLINE | ID: mdl-25651067

ABSTRACT

Vibrio vulnificus strains were isolated from oysters that were collected at the main seafood market in Mexico City. Strains were characterized with regard to vvhA, vcg genotype, PFGE, multilocus sequence typing (MLST), and rtxA1. Analyses included a comparison with rtxA1 reference sequences. Environmental (vcgE) and clinical (vcgC) genotypes were isolated at nearly equal percentages. PFGE had high heterogeneity, but the strains clustered by vcgE or vcgC genotype. Select housekeeping genes for MLST and primers that were designed for rtxA1 domains divided the strains into two clusters according to the E or C genotype. Reference rtxA1 sequences and those from this study were also clustered according to genotype. These results confirm that this genetic dimorphism is not limited to vcg genotyping, as other studies have reported. Some environmental C genotype strains had high similarity to reference strains, which have been reported to be virulent, indicating a potential risk for oyster consumers in Mexico City.


Subject(s)
Ostreidae/microbiology , Vibrio vulnificus/genetics , Animals , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Mexico , Molecular Sequence Data , Multilocus Sequence Typing , Phylogeny , Sequence Analysis, DNA , Vibrio vulnificus/classification , Vibrio vulnificus/isolation & purification , Vibrio vulnificus/physiology
13.
Nucleic Acids Res ; 40(22): 11189-201, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23066108

ABSTRACT

The study of cell-population heterogeneity in a range of biological systems, from viruses to bacterial isolates to tumor samples, has been transformed by recent advances in sequencing throughput. While the high-coverage afforded can be used, in principle, to identify very rare variants in a population, existing ad hoc approaches frequently fail to distinguish true variants from sequencing errors. We report a method (LoFreq) that models sequencing run-specific error rates to accurately call variants occurring in <0.05% of a population. Using simulated and real datasets (viral, bacterial and human), we show that LoFreq has near-perfect specificity, with significantly improved sensitivity compared with existing methods and can efficiently analyze deep Illumina sequencing datasets without resorting to approximations or heuristics. We also present experimental validation for LoFreq on two different platforms (Fluidigm and Sequenom) and its application to call rare somatic variants from exome sequencing datasets for gastric cancer. Source code and executables for LoFreq are freely available at http://sourceforge.net/projects/lofreq/.


Subject(s)
Genetic Variation , High-Throughput Nucleotide Sequencing/methods , Computer Simulation , Dengue Virus/genetics , Escherichia coli/genetics , Genomics/methods , High-Throughput Nucleotide Sequencing/standards , Humans , Mutation , Sensitivity and Specificity , Stomach Neoplasms/genetics , Viral Proteins/chemistry , Viral Proteins/genetics
14.
Article in English | MEDLINE | ID: mdl-20390836

ABSTRACT

Crassostrea virginica is an epibentic filter-feeding bivalve of economical importance in coastal lagoons of the Gulf of Mexico, locations with increasing inputs of heavy metals such as cadmium that have become environmental stressors. In this study, feeding and assimilation of the species were evaluated as physiological indicators of cadmium exposure. For this purpose, the filtration rate (FR), food assimilation (A) and assimilation efficiency (AE) of oysters from the Mandinga Lagoon, Veracruz, Mexico, were examined under sublethal and environmentally realistic cadmium concentrations (95 and 170 micro gCd L(-1)). Semi-static, 12-day bioassays were conducted with organisms placed into individual chambers and fed daily with Tetraselmis suecica. FR was calculated by measuring the depletion in algal density. Caloric contents of food and feces produced were also obtained. Condition Index (CI) and morphometric parameters were evaluated at the beginning and at the end of the assay. Total cadmium concentrations were quantified in water and tissue, and the metal bioconcentration factor (BCF) was calculated. Cadmium exposure significantly reduced FR in oysters (mean value: 0.64 L h(-1) and 0.44 L h(-1)) from control values (1.17 L h(-1)). Extreme values among results demonstrate the existence of a high FR (over 4 L h(-1)) mainly in control oysters, and this was associated with a better physiological condition; a low FR (under 2.5 L h(-1)) indicated metabolic stress as a consequence of Cd exposure. A and AE were significantly modified due to cadmium external levels, and time of exposure. FR and A were linearly related, and both decreased as metal BCF increased. Cadmium bioaccumulation was linearly related with external metal levels. The physiological deterioration of native C. virginica from Mandinga Lagoon was reflected in the alteration of FR, A and AE due to cadmium exposure in concentrations considered sublethal, lowering the feeding and assimilation capability of the organisms. The weight loss and mortality recorded in the oysters exposed to the highest metal concentration, was the final consequence of the overall adverse effect of cadmium exposure.


Subject(s)
Cadmium Compounds/toxicity , Chlorophyta/drug effects , Crassostrea/drug effects , Food Chain , Shellfish , Water Pollutants, Chemical/toxicity , Animals , Biological Assay , Body Weight/drug effects , Cadmium Compounds/analysis , Chlorophyta/metabolism , Crassostrea/metabolism , Environmental Monitoring , Longevity/drug effects , Mexico , Seasons , Toxicity Tests , Water Pollutants, Chemical/analysis
15.
Forensic Sci Int ; 192(1-3): 53-5, 2009 Nov 20.
Article in English | MEDLINE | ID: mdl-19709828

ABSTRACT

We analyzed the coding regions of the cardiac calcium-handling genes, ryanodine receptor 2 (RyR2) and calsequestrin 2 (CASQ2) for genetic variants in a healthy Chinese population (n=95) and in a cohort of 28 sudden unexplained death victims. Mutations in RyR2 and CASQ2 have been shown to alter calcium homeostasis during excitation-contraction coupling and predispose individuals to fatal cardiac arrhythmias. The genetic screening was accomplished by denaturing high-performance liquid chromatography and DNA sequencing methods. Genetic analysis revealed the following non-synonymous genetic variations: two reported RyR2 polymorphisms; 5654G>A (G1885E) and 5656G>A (G1886S), two reported CASQ2 polymorphisms; 196A>G (T66A) and 226G>A (V76M) and one novel CASQ2 mutation; 529G>C (E177Q). The functional significance of the novel CASQ2 mutation has not been evaluated and characterized. This study shows that multiple genetic variations of the RyR2 and CASQ2 genes exist in the two study populations. The inter-individual genetic variability may underlie the different susceptibility of individuals to developing ventricular tachycardia. The research results will be valuable for which future work involving clinical and forensic samples can be based upon to distinguish potential disease-associated mutations from common polymorphisms.


Subject(s)
Asian People/genetics , Calsequestrin/genetics , Mutation , Polymorphism, Genetic , Ryanodine Receptor Calcium Release Channel/genetics , Adolescent , Adult , Chromatography, High Pressure Liquid , Cohort Studies , Death, Sudden , Female , Forensic Genetics , Genetics, Population , Humans , Male , Middle Aged , Sequence Analysis, DNA , Singapore , Young Adult
16.
Life Sci ; 81(25-26): 1659-67, 2007 Dec 14.
Article in English | MEDLINE | ID: mdl-17963788

ABSTRACT

Sulfotransferases (SULTs) play an important role in the detoxification and bioactivation of endogenous compounds and xenobiotics. Studies on rat sulfotransferases had shown that SULT genes, like cytochrome P450 genes, can be regulated by ligands that bind nuclear receptors. For human SULT genes, the regulation of human SULT2A1 expression is currently the best characterized. In this study, we systematically examined the regulation of human SULT1A genes by glucocorticoids. Treatment of the human hepatocellular carcinoma derived HepG2 cells with 10(-7) M dexamethasone did not affect the SULT1A1 activity toward p-nitrophenol. In contrast, SULT1A3 activity toward dopamine was significantly induced. Transient transfection of the SULT1A3 5'-flanking region/luciferase reporter construct showed that SULT1A3 was responsive to dexamethasone and prednisolone in a concentration-dependent manner with maximal induction at 10(-7) M dexamethasone or 1 microM prednisolone. In addition, induction by dexamethasone was dependent on the level of expression of the glucocorticoid receptor. Analysis of the 5'-flanking region led to the identification of a putative glucocorticoid response element at position (-1211 to -1193) upstream of the transcription start site and deletion or mutation of this element resulted in a loss of response. In summary, the data from this study shows that the human SULT1A3 gene is inducible by glucocorticoids through a glucocorticoid receptor-mediated mechanism and the glucocorticoid response element at position (-1211 to -1193) is necessary for this induction.


Subject(s)
Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Enzymologic/genetics , Glucocorticoids/metabolism , Glucocorticoids/pharmacology , Sulfotransferases/genetics , Animals , Dexamethasone/metabolism , Dexamethasone/pharmacology , Hepatocytes/metabolism , Humans , Luciferases , Prednisolone/metabolism , Prednisolone/pharmacology , Rats , Receptors, Glucocorticoid/genetics , Response Elements/genetics , Sulfotransferases/drug effects , Transfection , Tumor Cells, Cultured
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