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1.
Int J Infect Dis ; 139: 59-68, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38029834

RESUMO

OBJECTIVE: The invasion of dengue virus (DENV)-2 Cosmopolitan genotype into the Philippines, where the Asian II genotype previously circulated challenges the principle of dengue serotype-specific immunity. Assessment of antibodies in this population may provide a mechanistic basis for how new genotypes emerge in dengue-endemic areas. METHODS: We evaluated the neutralizing antibody (nAb) and antibody-dependent enhancement (ADE) responses against the two genotypes using archived serum samples collected from 333 patients with confirmed dengue in Metro Manila, Philippines, before, during, and after the introduction of the Cosmopolitan genotype. We quantified nAb titers in baby hamster kidney (BHK-21) cells with or without the Fcγ receptor IIA (FcγRIIA) to detect the capacity of virus-antibody complexes to neutralize or enhance DENV. RESULTS: The nAb potency of the archived serum samples against the two genotypes was greatly affected by the presence of FcγRIIA. We found significant differences in nAb titers between the two genotypes in BHK-21 cells with FcγRIIA (P <0.0001). The archived serum samples were incapable of fully neutralizing the Cosmopolitan genotype, but instead strongly promoted its ADE compared to the Asian II genotype (P <0.0001). CONCLUSION: These results reinforce the role of pre-existing immunity in driving genotype shifts. Our finding that specific genotypes exhibit differing susceptibilities to ADE by cross-reactive antibodies may have implications for dengue vaccine development.


Assuntos
Vírus da Dengue , Dengue , Animais , Cricetinae , Humanos , Anticorpos Antivirais , Sorogrupo , Filipinas , Estudos Retrospectivos , Anticorpos Neutralizantes , Genótipo
2.
World J Gastrointest Oncol ; 13(12): 2101-2113, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-35070045

RESUMO

BACKGROUND: Colorectal cancer (CRC) ranks third in terms of incidence and second in mortality worldwide. In CRC, the silencing of mismatch repair genes, including the mutL homolog 1 (hMLH1) has been linked to microsatellite instability (MSI), the lengthening or shortening of microsatellite repeats. Very limited data have been presented so far on the link of hMLH1 methylation and MSI in Southeast Asia populations with sporadic CRC, and on its clinical significance. AIM: To investigate the significance of the MSI status and hMLH1 methylation in CRC Filipino patients. METHODS: Fifty-four sporadic CRC patients with complete clinical data were included in this study. Genomic DNA from CRC tumor biopsies and their normal tissue counterparts were profiled for MSI by high resolution melting (HRM) analysis using the Bethesda Panel of Markers (BAT25, BAT26, D2S123, D5S346, and D17S250). hMLH1 methylation screening was performed using bisulfite conversion and methylation specific polymerase chain reaction. Statistical analysis was conducted to calculate their associations to clinicopathological characteristics and survival relevance (Kaplan-Meier curves and the log-rank test). RESULTS: hMLH1 methylation was observed in 9% and 35% of CRC and normal samples, respectively. Higher incidence of consistently methylated hMLH1 found in both normal and CRC was noticed for relation to location of tumor (P < 0.05). As for MSI status, D2S123 the most common unstable microsatellite and MSI-high (MSI-H) was the most common MSI profile, counted for 46% and 50% of normal and CRC tissues, respectively. The presence of MSI-low (MSI-L) and microsatellite stable (MSS) was 43% and 11% for normal, and 31% and 19% for CRC samples. The mean month of patients' survival was shorter in patients whose normal and tumor tissues had methylated compared to those with unmethylated hMLH1 and with MSI-H compared to those with MSI-L/MSS (P < 0.05). This was supported by significant difference in Kaplan-Meier with log-rank analysis. This data indicated that hMLH1 methylation and high MSI status have prognostic value. CONCLUSION: This study showed the clinical significance of hMLH1 methylation and MSI status in sporadic CRC Filipino patients, especially in the normal part of the tumor.

4.
Jpn J Infect Dis ; 73(2): 176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32213721

RESUMO

Volume 72 no 6, p.413-419, 2019. Page 418, Acknowledgments "We would like to thank all staff and members of the Department of Virology, NEKKEN, Nagasaki University, Japan for providing technical support and advice. Our special thanks to the staff of the Pavilion II and the Central Laboratory of San Lazaro Hospital for their kind assistance during patient recruitment and data collection. We are also very grateful for the support of the Senior Vice President and Head of Research and Biotechnology (R&B) Group of St. Luke's Medical Center, Dr. Isaac David E. Ampil II. Finally, our sincere thanks to the members of R&B's dengue research group for kindly preparing the samples to be transported to NEKKEN." should read "This research was supported by grants from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP18fm0108001, JP19fm0108001 (Japan Initiative for Global Research Network on Infectious Diseases (J-GRID)), AMED Research on Emerging and Re-emerging Infectious Diseases (19fk0108035j0003) and e-ASIA Joint Research Program and; Philippine Council for Health Research and Development (PCHRD) of the Department of Science and Technology (DOST), Philippines, with partial support from the Research and Biotechnology of St. Luke's Medical Center (R&B-SLMC), Philippines (Project No. 07-024). Funders have no role in the study design, data collection, and interpretation, or the decision to submit this work for publication. We would like to thank all staff and members of the Department of Virology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan, for providing technical support and advice. Our special thanks to the staff of the Pavilion II and the Central Laboratory of San Lazaro Hospital for their kind assistance during patient recruitment and data collection. We are also very grateful for the support of the Senior Vice President and Head of Research and Biotechnology (R&B) Group of St. Luke's Medical Center, Dr. Isaac David E. Ampil II. Finally, our sincere thanks to the members of R&B's Dengue Research Group for kindly preparing the samples to be transported to NEKKEN."

5.
Jpn J Infect Dis ; 72(6): 413-419, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31474703

RESUMO

Dengue remains a major public health problem in the Philippines. In this study, we determined the circulating dengue serotypes in the Philippines during the 2015-2017 outbreaks using a total of 678 serum samples from 537 individual dengue patients. Following an increase in the number of DENV-4 patients in recent years, we conducted a comprehensive molecular and epidemiology analysis on the DENV-4 strains isolated recently in the Philippines. Two genotypes of DENV-4 have been isolated in the Philippines since 1956: GI and GIIa. The GIIa DENV strains that were isolated in the present study were closely related to a distinct group of GIIa strains that were isolated from the Philippines in 2004. A majority of the isolates of this sub-group have been identified in the Philippines, suggesting that this lineage may have been introduced in the Philippines, and evolved to form the distinct sub-group within GIIa strains. The increase in DENV-4 activity also coincided with the appearance of the GIIa subgroup and the phasing-out of the GI lineage in the Philippines. Overall, our study demonstrates a shift in DENV-4 genotype and epidemic dynamics in a hyperendemic region, suggesting the importance of DENV genetic evolution in establishing and sustaining transmission.


Assuntos
Vírus da Dengue/genética , Dengue/epidemiologia , Epidemias/estatística & dados numéricos , Adolescente , Adulto , Criança , Dengue/virologia , Vírus da Dengue/imunologia , Evolução Molecular , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Filipinas/epidemiologia , Filogenia , RNA Viral/genética , Análise de Sequência de DNA , Sorogrupo , Adulto Jovem
6.
Leuk Lymphoma ; 58(5): 1178-1183, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27724056

RESUMO

Addressing the global burden of cancer, understanding its diverse biology, and promoting appropriate prevention and treatment strategies around the world has become a priority for the United Nations and International Atomic Energy Agency (IAEA), the WHO, and International Agency for Research on Cancer (IARC). The IAEA sponsored an international prospective cohort study to better understand biology, treatment response, and outcomes of diffuse large B-cell lymphoma (DLBCL) in low and middle-income countries across five UN-defined geographical regions. We report an analysis of biological variation in DLBCL across seven ethnic and environmentally diverse populations. In this cohort of 136 patients treated to a common protocol, we demonstrate significant biological differences between countries, characterized by a validated prognostic gene expression score (p < .0001), but International Prognostic Index (IPI)-adjusted survivals in all participating countries were similar. We conclude that DLBCL treatment outcomes in these populations can be benchmarked to international standards, despite biological heterogeneity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/epidemiologia , Adulto , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Biomarcadores Tumorais , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Saúde Global , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prednisona/uso terapêutico , Prognóstico , Rituximab , Resultado do Tratamento , Vincristina/uso terapêutico
7.
Oncotarget ; 7(50): 83319-83329, 2016 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-27825111

RESUMO

As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S. Korea, Thailand and Turkey). Using the Kaplan-Meier and log rank test on patients (n=162) and two mortality risk groups (with those above and below the mean representing high and low risk groups) confirmed that the 6-gene predictor score correlates significantly with overall survival (OS, p<0.01) but not with event free survival (EFS, p=0.18). Adding the International Prognostic Index (IPI) shows that the 6-gene predictor score correlates significantly with high IPI scores for OS (p<0.05), whereas those with low IPI scores show a trend not reaching significance (p=0.08). This study defined an effective and economical qRT-PCR strategy and validated the 6-gene score as a predictor of OS in an international setting.


Assuntos
Biomarcadores Tumorais/genética , Fixadores/química , Formaldeído/química , Perfilação da Expressão Gênica/métodos , Linfoma Difuso de Grandes Células B/genética , Inclusão em Parafina , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fixação de Tecidos/métodos , Transcriptoma , Idoso , Ásia , Biópsia , Intervalo Livre de Doença , Europa (Continente) , Feminino , Perfilação da Expressão Gênica/normas , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real/normas , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , América do Sul , Fatores de Tempo
8.
mBio ; 6(2)2015 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-25900650

RESUMO

UNLABELLED: Cholera continues to be a global threat, with high rates of morbidity and mortality. In 2011, a cholera outbreak occurred in Palawan, Philippines, affecting more than 500 people, and 20 individuals died. Vibrio cholerae O1 was confirmed as the etiological agent. Source attribution is critical in cholera outbreaks for proper management of the disease, as well as to control spread. In this study, three V. cholerae O1 isolates from a Philippines cholera outbreak were sequenced and their genomes analyzed to determine phylogenetic relatedness to V. cholerae O1 isolates from recent outbreaks of cholera elsewhere. The Philippines V. cholerae O1 isolates were determined to be V. cholerae O1 hybrid El Tor belonging to the seventh-pandemic clade. They clustered tightly, forming a monophyletic clade closely related to V. cholerae O1 hybrid El Tor from Asia and Africa. The isolates possess a unique multilocus variable-number tandem repeat analysis (MLVA) genotype (12-7-9-18-25 and 12-7-10-14-21) and lack SXT. In addition, they possess a novel 15-kb genomic island (GI-119) containing a predicted type I restriction-modification system. The CTXΦ-RS1 array of the Philippines isolates was similar to that of V. cholerae O1 MG116926, a hybrid El Tor strain isolated in Bangladesh in 1991. Overall, the data indicate that the Philippines V. cholerae O1 isolates are unique, differing from recent V. cholerae O1 isolates from Asia, Africa, and Haiti. Furthermore, the results of this study support the hypothesis that the Philippines isolates of V. cholerae O1 are indigenous and exist locally in the aquatic ecosystem of the Philippines. IMPORTANCE: Genetic characterization and phylogenomics analysis of outbreak strains have proven to be critical for probing clonal relatedness to strains isolated in different geographical regions and over time. Recently, extensive genetic analyses of V. cholerae O1 strains isolated in different countries have been done. However, genome sequences of V. cholerae O1 isolates from the Philippines have not been available for epidemiological investigation. In this study, molecular typing and phylogenetic analysis of Vibrio cholerae isolated from both clinical and environmental samples in 2011 confirmed unique genetic features of the Philippines isolates, which are helpful to understand the global epidemiology of cholera.


Assuntos
Cólera/epidemiologia , Cólera/microbiologia , Surtos de Doenças , Genes Bacterianos , Vibrio cholerae O1/genética , Vibrio cholerae O1/isolamento & purificação , Análise por Conglomerados , Farmacorresistência Bacteriana , Genoma Bacteriano , Genótipo , Repetições Minissatélites , Dados de Sequência Molecular , Tipagem Molecular , Filipinas/epidemiologia , Filogenia , Recombinação Genética , Análise de Sequência de DNA , Homologia de Sequência , Vibrio cholerae O1/classificação
9.
Mol Biol Rep ; 42(3): 673-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25391769

RESUMO

Hepatitis B virus (HBV) is one of the most prevalent viral infections worldwide. Nearly 400 million individuals are chronic carriers of HBV. The aim of the present study was to determine the frequency of human interleukin 28B (IL28B) variants among treatment naive Filipino patients clinically diagnosed with chronic hepatitis B (CHB), and to compare the IL28B frequency distribution with various ethnic populations. Fifty-seven CHB patients and 43 normal controls were enrolled in this study. Real-time PCR was performed using the TaqMan genotyping assay for IL28B rs12979860. The allelic frequencies among normal controls were 0.94 and 0.06 for the IL28B rs12979860 C and T alleles, respectively. Eighty-eight percent were identified as homozygous for the IL28B C/C genotype and 12% were identified as heterozygous for the IL28B C/T genotype. Among CHB patients, the allelic frequencies were 0.90 for the IL28B C allele and 0.10 for the IL28B T allele. No IL28B T/T genotype was observed between the two groups. No significant difference in the distribution of IL28B genotypes was observed between normal controls and CHB patients. Allelic frequencies of IL28B among Filipinos were similar with other Asian populations but significantly different from Caucasians. The frequency of rs12979860 C>T variants among Filipino CHB patients has not yet been reported. These data provided new insight into the geographical frequency distribution of IL28B variants. Further studies are needed to determine the possible association between IL28B variants and response to pegylated-interferon-α plus ribavirin combination therapy among Filipino patients chronically infected with HBV.


Assuntos
Povo Asiático/genética , Frequência do Gene , Vírus da Hepatite B , Hepatite B Crônica/genética , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Sequência de Bases , Estudos de Casos e Controles , Craniossinostoses , Feminino , Predisposição Genética para Doença , Vírus da Hepatite B/genética , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Holoprosencefalia , Humanos , Interferons , Masculino , Pessoa de Meia-Idade , Filipinas , Adulto Jovem
10.
Int J Clin Exp Med ; 7(8): 2129-36, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25232397

RESUMO

Genome-wide association studies have shown that a non-synonymous single nucleotide polymorphism characterized by a C-to-G change encoding an isoleucine-to-methionine substitution at amino acid position 148 in the human patatin-like phospholipase 3 (PNPLA3) gene was found to be associated with non-alcoholic fatty liver disease (NAFLD) and advanced liver damage. A hospital-based study was conducted to determine the distribution of PNPLA3 genotypes among patients clinically diagnosed and histologically confirmed with NAFLD and among normal controls. We also compared the allelic frequencies of PNPLA3 with different ethnic populations. More importantly, we evaluated the association between PNPLA3 genetic variation and risk of developing NAFLD among Filipinos. Real-time PCR was performed using the Taqman SNP genotyping assay for rs738409. Nucleotide sequencing was performed to confirm the PNPLA3 genotypes. Allelic frequencies among normal controls were 0.83 and 0.17 for the PNPLA3 C and PNPLA3 G alleles, respectively. Calculated frequencies in Hardy Weinberg Equilibrium were 72% for PNPLA3 C/C, 22% for PNPLA3 C/G, and 6% for PNPLA3 G/G genotype. There is a significant difference in the distribution of PNPLA3 genotypes between normal controls and NAFLD patients (p = 0.0172). However, there was no significant association found between PNPLA3 genotypes and risk of developing NAFLD after controlling for possible confounding effects (p = 0.0574). Allelic frequencies of PNPLA3 among Filipinos were statistically different from Hispanics, Japanese, and Han Chinese. In conclusion, genetic variation in PNPLA3 rs738409 C>G seems to be associated with NAFLD among Filipinos. Further studies are needed to replicate our observations in an independent larger population.

11.
Genome Announc ; 2(3)2014 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-24970822

RESUMO

Chikungunya virus is an alphavirus of the Togaviridae family, which causes a febrile illness with arthralgia in humans. We report here on the complete genome sequence of chikungunya virus strain CHIKV-13-112A isolated from a patient in the Philippines who was suspected to have dengue virus. Phylogenetic analysis revealed that the strain is of the Asian genotype.

12.
J Gen Virol ; 95(Pt 6): 1390-1395, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24646751

RESUMO

In 2005, we isolated a new species of virus from mosquitoes in the Philippines. The virion was elliptical in shape and had a short single projection. The virus was named Tanay virus (TANAV) after the locality in which it was found. TANAV genomic RNA was a 9562 nt+poly-A positive strand, and polycistronic. The longest ORF contained putative RNA-dependent RNA polymerase (RdRP); however, conserved short motifs in the RdRP were permuted. TANAV was phylogenetically close to Negevirus, a recently proposed taxon of viruses isolated from haemophagic insects, and to some plant viruses, such as citrus leprosis virus C, hibiscus green spot virus and blueberry necrotic ring blotch virus. In this paper, we describe TANAV and the permuted structure of its RdRP, and discuss its phylogeny together with those of plant viruses and negevirus.


Assuntos
Culicidae/virologia , Vírus de Insetos/isolamento & purificação , Vírus de RNA/isolamento & purificação , Vírus não Classificados/isolamento & purificação , Sequência de Aminoácidos , Animais , Culex/virologia , Genoma Viral , Vírus de Insetos/classificação , Vírus de Insetos/genética , Microscopia Eletrônica de Transmissão , Dados de Sequência Molecular , Fases de Leitura Aberta , Filipinas , Filogenia , Vírus de Plantas/genética , Vírus de RNA/classificação , Vírus de RNA/genética , RNA Polimerase Dependente de RNA/genética , Homologia de Sequência de Aminoácidos , Proteínas Virais/genética , Vírion/ultraestrutura , Vírus não Classificados/classificação , Vírus não Classificados/genética
13.
J Med Virol ; 86(2): 209-16, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24009186

RESUMO

Point mutations and multiple variants across the "a" determinant can destroy the antigenicity and immunogenicity of hepatitis B virus (HBV) leading to false negative assay and vaccine escape. In this study, the presence of surface gene variants of HBV was investigated among patients clinically diagnosed with chronic hepatitis B and positive for HBV DNA from 2002 to 2009. Sequence analysis of the surface gene of HBV showed that 23 (43%) of the 53 isolates had variations. Out of the 23 isolates, 15 (65%) exhibited single or multiple substitutions, which resulted to specific amino acid changes. The remaining 8 (35%) isolates had silent mutations. The amino acid substitution M133T which was associated with failure of HBsAg detection was found in one isolate (7%, 1/15), while the amino acid substitution D144A which was associated with vaccine escape was observed in one isolate (7%, 1/15). No G145R mutation was observed. Of the 15 isolates with identified single or multiple substitutions, 6 (40%) were found to have unique sequences which caused changes in the hydrophobicity profile in the protein. Unique sequence variants at amino acid positions M103I, L109P, S117R, F134I, and S136L found in this study have not yet been reported. These data should be taken into account when developing next generation HBV assays to detect both common and unique variants, and when new HBV vaccines will be designed.


Assuntos
Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/virologia , Substituição de Aminoácidos , DNA Viral/química , DNA Viral/genética , Erros de Diagnóstico , Genótipo , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/classificação , Vírus da Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/prevenção & controle , Humanos , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Filipinas , Mutação Puntual , Análise de Sequência de DNA
14.
Trop Med Health ; 42(4): 145-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25589879

RESUMO

We report the case of a 76-year old Filipino male who presented with pain, redness, and blurring of vision of the right eye. Corneal scraping was done and sent to the St. Luke's Research and Biotechnology Group for detection and identification of the infectious agent. Morphological detection was performed by allowing the organism from the scraping to grow in 1.5% non-nutrient agar plate with heat-killed E. coli. Trophozoites with acanthopodia and double-walled cysts characteristic of Acanthamoeba were observed within the first and second week of observations, respectively. Molecular identification of the amoebae at the genus level based on the presence of Acanthamoeba-specific amplimer S1, ASA.S1 confirmed the morphological identification. Genotyping through sequence revealed that the organism belonged to T4, which is the genotype commonly present in the eye of keratitis patients.

15.
Acta Medica Philippina ; : 17-22, 2014.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-633713

RESUMO

OBJECTIVE: This study aimed to detect the presence of microsatellite (MSI) and loss of heterozygosity (LOH) of the Deleted in Colorectal Cancer (DCC) gene in normal and tumor tissues of Filipino colorectal cancer patients and examine its correlation with age, gender, tumor grade, tumor stage and site of lesion.METHODS: Paired frozen normal and tumor tissues from thirtynine (39) patients with colorectal adenocarcinoma were used by polymerase chain reaction (PCR). Single strand conformation polymorphism - polyacrylamide gel electrophoresis (SSCP - PAGE) was used to determine MSI and restriction fragment length polymorphism (RFLP) was used to study LOH.RESULTS: Based on our data, out of the 39 patients, 10 showed LOH of the DCC gene using the LOH markers VNTR, M2 and M3, while no MSI was detected in the samples using the MSI markers BAT25 and BAT26. Correlation with clinicopathological characteristics showed that there is significance for the site of lesion. The LOH has correclation with tumor samples from the colon but not with those from the rectum.CONCLUSION: Preliminary screening for MSI and LOH of the DCC gene shows that occurrences of colorectal cancer among Filipino patients can be correlated with LOH of the DCC gene with colorectal cancer in a Filipino sample population.


Assuntos
Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Adulto , Genes DCC , Polimorfismo Conformacional de Fita Simples , Neoplasias Colorretais , Adenocarcinoma , Perda de Heterozigosidade
16.
J Med Virol ; 85(7): 1258-66, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23595687

RESUMO

In Myanmar, dengue fever (DF)/dengue hemorrhagic fever (DHF) is one of the leading causes of morbidity and mortality among children. From Pyinmana Hospital in 2004 and Mandalay Children Hospital in 2006, 160 patients diagnosed clinically to have DHF/dengue shock syndrome (DSS) were examined for immunoglobulin M (IgM) and IgG levels. A focus reduction neutralization test was also used to determine primary or secondary dengue virus (DENV) infection. By using IgM-capture ELISA, 139 cases were confirmed as DENV infections. Of these IgM-positives, 94 samples were collected 7-24 days from the onset of illness, to which 13 (14%) and 81 (86%) were determined to be primary and secondary DENV infections, respectively. The 13 primary DENV infection cases were spread among the various severity groups (DHF grade I-IV and DSS) and represented age groups ranging from <1 year of age to 9 years of age. The patients in these primary infection cases showed a remarkably high IgM with a low IgG titer response compared with the secondary infection cases. No significant differences were observed in IgG titers with clinical severity. The data obtained in this study suggest that primary DENV infection cases exist certainly among DHF/DSS cases in Myanmar, and that additional mechanism(s) aside from the antibody-dependent enhancement mechanism could have influenced the clinical severity in DHF/DSS cases.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Dengue/imunologia , Dengue/imunologia , Dengue/patologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Masculino , Mianmar , Testes de Neutralização
17.
Int J Mol Epidemiol Genet ; 3(2): 115-21, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22724048

RESUMO

A hospital-based cross-sectional study was conducted to determine the allelic and genotype frequencies in the genes encoding for catechol-O-methyltransferase and CYP2D6*10 among healthy volunteers and patients clinically diagnosed with cancer pain. PCR-RFLP was used to identify COMT and CYP2D6*10 genotypes. Allelic frequencies among healthy volunteer Filipinos were 0.83 and 0.17 for the COMT Val and COMT Met alleles, respectively. Calculated frequencies in Hardy-Weinberg equilibrium (HWE) were 73% for COMT Val/Val, 26% for COMT Val/Met, and 1% for COMT Met/Met genotype. For CYP2D6*10, allelic frequencies in HWE among volunteers were 0.46 for the C allele and 0.54 for the T allele. Twenty percent were identified as homozygous for the wild-type C/C genotype, 56% were identified as heterozygous for the C/T genotype, and 24% were identified as homozygous for the T/T variant genotype. No significant differences in COMT and CYP2D6*10 allele frequencies between cancer patients and healthy volunteers were noted. Our data demonstrated that the allele frequencies of COMT and CYP2D6*10 in the Filipino healthy volunteers were similar with other Asians but markedly different from Caucasian populations.

18.
Int J Mol Epidemiol Genet ; 3(2): 153-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22724052

RESUMO

The glutathione S-transferase (GST) supergene family is made up of four gene families responsible for the biotransformation of drugs and other xenobiotics. Genetic variations in this supergene family influence individual detoxification levels and may contribute to the development of cancer. A hospital-based case-control study was conducted to evaluate the association between GST polymorphism among Filipino patients positive for hepatitis B virus (HBV DNA) and clinically diagnosed as either with chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma as well as normal individuals negative for HBV infection. Multiplex PCR was used to detect the presence or absence of the GSTT1 and GSTM1 polymorphisms in peripheral blood. DNA sequencing of the S gene region of the virus was used to determine the predominant genotype found among HBV-infected patients. Our results showed that the odds of having a chronic liver disease is only 0.95 (95% CI 0.58-1.57) among those with GSTT1 null genotype compared to those with GSTT1+ genotype. On the other hand, the odds of chronic liver disease is 17.85 times (95% CI 7.34-43.45) for those with GSTM1 null genotype compared to those with GSTM1+ genotype. Using the GSTT1+/GSTM1+ genotype as the reference, both GSTT1+/GSTM1- (OR 16.61; 95% CI 6.69-41.22) and GSTT1-/GSTM1- (OR 11.91; 95% CI 4.48-31.66) genotypes seem to be risk factors for chronic liver disease. From our observations, we conclude that polymorphism in GSTM1 null genotype (OR 17.85; 95% CI 7.34-43.45) seem to be associated with an increased risk of chronic liver disease among Filipinos.

19.
J Infect Dis ; 205(8): 1321-9, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22383677

RESUMO

BACKGROUND: The mechanisms of thrombocytopenia and platelet phagocytosis in dengue illness are not fully understood. METHODS: A prospective hospital-based study was conducted to examine the relationships between platelet counts, serum thrombopoietin (TPO) levels, and platelet apoptosis and phagocytosis in 81 patients with secondary dengue virus (DV) infections and 38 healthy volunteers. The apoptosis and phagocytosis of cultured platelets after exposure to DV were also examined. RESULTS: Platelet apoptosis, platelet phagocytosis, and serum TPO levels were increased significantly in patients during the acute and early convalescence phases compared with levels observed in patients during the convalescence phase and in healthy volunteers. A significant correlation between platelet apoptosis and platelet phagocytosis was also observed in these patients. Platelet phagocytosis was inhibited significantly by the D89E mutant, which carries a point mutation in the RGD motif of milk fat globule-epidermal growth factor 8, a phosphatidylserine-recognizing bridge molecule. DV-induced platelet apoptosis and increased phagocytosis of DV-induced apoptotic platelets was confirmed using in vitro assays. CONCLUSIONS: Our data suggest an increased phagocytosis of DV-induced apoptotic platelets by macrophages via a phosphatidylserine-recognizing pathway in secondary DV infection. Accelerated platelet clearance, however, was overcome by TPO-induced enhanced thrombopoiesis in these patients. CLINICAL TRIALS REGISTRATION: UMIN000004835.


Assuntos
Apoptose/fisiologia , Plaquetas/citologia , Dengue/patologia , Macrófagos/fisiologia , Adulto , Plaquetas/fisiologia , Estudos de Casos e Controles , Humanos , Contagem de Plaquetas , Trombopoetina , Adulto Jovem
20.
J Bacteriol ; 194(2): 542-3, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22207747

RESUMO

The first shotgun genome sequence of a microbial pathogen from the Philippines is reported. Yersinia enterocolitica subsp. palearctica strain PhRBD_Ye1 is the first Y. enterocolitica strain sequenced from an animal source, swine, which is a natural source of yersiniosis. The closest phylogenetic match is a human clinical isolate from Germany.


Assuntos
Genoma Bacteriano , Yersiniose/microbiologia , Yersinia enterocolitica/genética , Gastroenteropatias/epidemiologia , Gastroenteropatias/microbiologia , Humanos , Dados de Sequência Molecular , Filipinas/epidemiologia , Yersiniose/epidemiologia
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