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1.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-33753512

RESUMEN

Island Southeast Asia has recently produced several surprises regarding human history, but the region's complex demography remains poorly understood. Here, we report ∼2.3 million genotypes from 1,028 individuals representing 115 indigenous Philippine populations and genome-sequence data from two ∼8,000-y-old individuals from Liangdao in the Taiwan Strait. We show that the Philippine islands were populated by at least five waves of human migration: initially by Northern and Southern Negritos (distantly related to Australian and Papuan groups), followed by Manobo, Sama, Papuan, and Cordilleran-related populations. The ancestors of Cordillerans diverged from indigenous peoples of Taiwan at least ∼8,000 y ago, prior to the arrival of paddy field rice agriculture in the Philippines ∼2,500 y ago, where some of their descendants remain to be the least admixed East Asian groups carrying an ancestry shared by all Austronesian-speaking populations. These observations contradict an exclusive "out-of-Taiwan" model of farming-language-people dispersal within the last four millennia for the Philippines and Island Southeast Asia. Sama-related ethnic groups of southwestern Philippines additionally experienced some minimal South Asian gene flow starting ∼1,000 y ago. Lastly, only a few lowlanders, accounting for <1% of all individuals, presented a low level of West Eurasian admixture, indicating a limited genetic legacy of Spanish colonization in the Philippines. Altogether, our findings reveal a multilayered history of the Philippines, which served as a crucial gateway for the movement of people that ultimately changed the genetic landscape of the Asia-Pacific region.


Asunto(s)
Migración Humana/historia , Grupos de Población/historia , Agricultura , Asia Sudoriental/etnología , Australia/etnología , Femenino , Flujo Genético , Genómica , Historia Antigua , Humanos , Masculino , Oryza , Filipinas , Grupos de Población/genética , Taiwán/etnología
2.
Mol Biol Evol ; 38(10): 4149-4165, 2021 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-33170928

RESUMEN

The Taiwanese people are composed of diverse indigenous populations and the Taiwanese Han. About 95% of the Taiwanese identify themselves as Taiwanese Han, but this may not be a homogeneous population because they migrated to the island from various regions of continental East Asia over a period of 400 years. Little is known about the underlying patterns of genetic ancestry, population admixture, and evolutionary adaptation in the Taiwanese Han people. Here, we analyzed the whole-genome single-nucleotide polymorphism genotyping data from 14,401 individuals of Taiwanese Han collected by the Taiwan Biobank and the whole-genome sequencing data for a subset of 772 people. We detected four major genetic ancestries with distinct geographic distributions (i.e., Northern, Southeastern, Japonic, and Island Southeast Asian ancestries) and signatures of population mixture contributing to the genomes of Taiwanese Han. We further scanned for signatures of positive natural selection that caused unusually long-range haplotypes and elevations of hitchhiked variants. As a result, we identified 16 candidate loci in which selection signals can be unambiguously localized at five single genes: CTNNA2, LRP1B, CSNK1G3, ASTN2, and NEO1. Statistical associations were examined in 16 metabolic-related traits to further elucidate the functional effects of each candidate gene. All five genes appear to have pleiotropic connections to various types of disease susceptibility and significant associations with at least one metabolic-related trait. Together, our results provide critical insights for understanding the evolutionary history and adaption of the Taiwanese Han population.


Asunto(s)
Pueblo Asiatico , Genoma , Pueblo Asiatico/genética , Estudio de Asociación del Genoma Completo , Haplotipos , Humanos , Polimorfismo de Nucleótido Simple
3.
BMC Evol Biol ; 19(1): 64, 2019 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-30813905

RESUMEN

BACKGROUND: Despite attempts in retracing the history of the Thao people in Taiwan using folktales, linguistics, physical anthropology, and ethnic studies, their history remains incomplete. The heritage of Thao has been associated with the Pazeh Western plains peoples and several other mountain peoples of Taiwan. In the last 400 years, their culture and genetic profile have been reshaped by East Asian migrants. They were displaced by the Japanese and the construction of a dam and almost faced extinction. In this paper, genetic information from mitochondrial DNA (mtDNA), Histoleucocyte antigens (HLA), and the non-recombining Y chromosome of 30 Thao individuals are compared to 836 other Taiwan Mountain and Plains Aborigines (TwrIP & TwPp), 384 Non-Aboriginal Taiwanese (non-TwA) and 149 Continental East Asians. RESULTS: The phylogeographic analyses of mtDNA haplogroups F4b and B4b1a2 indicated gene flow between Thao, Bunun, and Tsou, and suggested a common ancestry from 10,000 to 3000 years ago. A claim of close contact with the heavily Sinicized Pazeh of the plains was not rejected and suggests that the plains and mountain peoples most likely shared the same Austronesian agriculturist gene pool in the Neolithic. CONCLUSIONS: Having been moving repeatedly since their arrival in Taiwan between 6000 and 4500 years ago, the Thao finally settled in the central mountain range. They represent the last plains people whose strong bonds with their original culture allowed them to preserve their genetic heritage, despite significant gene flow from the mainland of Asia. Representing a considerable contribution to the genealogical history of the Thao people, the findings of this study bear on ongoing anthropological and linguistic debates on their origin.


Asunto(s)
Pueblo Asiatico/genética , Cromosomas Humanos Y/genética , Variación Genética , Antígenos HLA/genética , ADN Mitocondrial/química , ADN Mitocondrial/genética , Flujo Génico , Genética de Población , Haplotipos , Humanos , Masculino , Filogeografía , Análisis de Secuencia de ADN , Taiwán
4.
BMC Evol Biol ; 19(1): 212, 2019 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-31747896

RESUMEN

Following publication of the original article [1], we have been notified that Additional file 3 was published with track changes.

5.
BMC Surg ; 19(1): 135, 2019 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-31510991

RESUMEN

BACKGROUND: Poorly differentiated neuroendocrine carcinomas (NECs) originating from the gastrointestinal (GI) tract are rare and very highly malignant disease with a poor prognosis. Poorly differentiated NECs most commonly arise in the esophagus and the large bowel; however, they may occur within virtually any portion of the GI tract. It is known, however, that they do not typically occur in the small intestine. CASE REPORT: A 21-year-old woman visited an emergency room with acute abdominal pain that commenced 2 days prior to her presentation. Thereafter, a computed tomography (CT) scan was notable for a small-intestine perforation, and huge masses were observed in the small intestine and the mesentery. The mass that was located at the ileum site is approximately 100 cm above the ileocecal (IC) valve, and while it is located on the anti-mesenteric border and it seems that luminal narrowing had occurred, an obstruction is absent. Also, a same-nature mass is on the mesentery. The pathologic reports confirmed a small-cell-type NEC with a mass size of 7.5 × 6.5 cm. The mitotic count is up to 24/10 high-power fields (HPFs), the results of the immunohistochemical stain are positive for CD56 and synaptophysin, and the Ki-67 level is 50%. %. After the operation, she was treated with Etoposide-Cisplatin (EP) chemotheraphy. Stable disease was seen during Etoposide-Cisplatin chemotheraphy. Liver metastasis was also confirmed after chemotheraphy. Additionally, Irinotecan and cisplatin were used for 3 cycles, but progression of disease, neutropenic fever, thrombocytopenia, general weakness persisted. Eventually, she died 1 year and 6 months after surgery. CONCLUSION: Ileum-located NECs are diagnosed very rarely. The most common locations for these tumors along the GI tract are the esophagus and the large intestine, but they can arise anywhere. The prognosis for NECs is poor due to the metastatic disease of most patients at the time of diagnosis. The role of adjuvant treatment requires further evaluation for the attainment of a better understanding of the overall treatment effect.


Asunto(s)
Carcinoma Neuroendocrino/diagnóstico , Carcinoma de Células Pequeñas/diagnóstico , Neoplasias Hepáticas/secundario , Carcinoma Neuroendocrino/patología , Femenino , Humanos , Íleon/patología , Pronóstico , Tomografía Computarizada por Rayos X , Adulto Joven
7.
Hum Genet ; 135(3): 309-26, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26781090

RESUMEN

There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The "out-of-Taiwan" model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion.


Asunto(s)
Pueblo Asiatico/genética , ADN Mitocondrial/genética , Genoma Humano , Asia Sudoriental , Cromosomas Humanos Y/genética , Bases de Datos Genéticas , Femenino , Estudios de Asociación Genética , Sitios Genéticos , Humanos , Masculino , Modelos Genéticos , Filogenia , Filogeografía , Polimorfismo de Nucleótido Simple , Reproducibilidad de los Resultados
8.
Pharmacology ; 96(1-2): 68-75, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26089136

RESUMEN

AIMS: To compare the pharmacokinetics, pharmacodynamics, and safety of sarpogrelate between controlled-release (CR) and immediate-release (IR) formulations after multiple-dose administration. METHODS: This study was a randomized, open-label, 2-period, 2-treatment, crossover study in healthy subjects. All subjects received CR sarpogrelate 300 mg once daily and IR sarpogrelate 100 mg three times daily by random order each for 3 days with a 7-day washout period. Serial blood sampling was performed over 24 h. Pharmacokinetic parameters were determined by noncompartmental methods. Platelet aggregation to collagen, measured by light transmission aggregometry, was reported as maximal platelet aggregation. RESULTS: Thirty-two subjects completed the study. CR sarpogrelate increased rapidly, reaching Cmax in 1.25 h (vs. 1.00 h in IR sarpogrelate) and declined with a t1/2 of 3.59 h (vs. 1.12 h in IR sarpogrelate). The 90% CIs for the geometric mean ratio of AUCτ and Cmax,ss between IR and CR formulations were 1.18 to 1.40 and 0.99 to 1.29, respectively. The degree of inhibition of platelet aggregation was similar between two formulations. CONCLUSIONS: CR sarpogrelate showed slightly higher systemic exposure and similar peak concentration compared with IR sarpogrelate. The profiles of pharmacodynamics and safety were comparable between two formulations.


Asunto(s)
Preparaciones de Acción Retardada , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/farmacocinética , Succinatos/administración & dosificación , Succinatos/farmacocinética , Adulto , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Femenino , Humanos , Masculino , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/farmacología , Succinatos/efectos adversos , Succinatos/farmacología , Adulto Joven
9.
Am J Hum Genet ; 88(2): 239-47, 2011 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-21295281

RESUMEN

The "Polynesian motif" defines a lineage of human mtDNA that is restricted to Austronesian-speaking populations and is almost fixed in Polynesians. It is widely thought to support a rapid dispersal of maternal lineages from Taiwan ~4000 years ago (4 ka), but the chronological resolution of existing control-region data is poor, and an East Indonesian origin has also been proposed. By analyzing 157 complete mtDNA genomes, we show that the motif itself most likely originated >6 ka in the vicinity of the Bismarck Archipelago, and its immediate ancestor is >8 ka old and virtually restricted to Near Oceania. This indicates that Polynesian maternal lineages from Island Southeast Asia gained a foothold in Near Oceania much earlier than dispersal from either Taiwan or Indonesia 3-4 ka would predict. However, we find evidence in minor lineages for more recent two-way maternal gene flow between Island Southeast Asia and Near Oceania, likely reflecting movements along a "voyaging corridor" between them, as previously proposed on archaeological grounds. Small-scale mid-Holocene movements from Island Southeast Asia likely transmitted Austronesian languages to the long-established Southeast Asian colonies in the Bismarcks carrying the Polynesian motif, perhaps also providing the impetus for the expansion into Polynesia.


Asunto(s)
ADN Mitocondrial/genética , Flujo Génico , Genética de Población , Haplotipos/genética , Nativos de Hawái y Otras Islas del Pacífico/genética , Polimorfismo Genético/genética , Asia Sudoriental , Humanos , Indonesia , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa , Polinesia , Taiwán
10.
Proc Biol Sci ; 281(1774): 20132072, 2014 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-24225453

RESUMEN

We present, to our knowledge, the first quantitative evidence that music and genes may have coevolved by demonstrating significant correlations between traditional group-level folk songs and mitochondrial DNA variation among nine indigenous populations of Taiwan. These correlations were of comparable magnitude to those between language and genes for the same populations, although music and language were not significantly correlated with one another. An examination of population structure for genetics showed stronger parallels to music than to language. Overall, the results suggest that music might have a sufficient time-depth to retrace ancient population movements and, additionally, that it might be capturing different aspects of population history than language. Music may therefore have the potential to serve as a novel marker of human migrations to complement genes, language and other markers.


Asunto(s)
Evolución Molecular , Lenguaje , Música , Pueblo Asiatico/genética , ADN Mitocondrial/química , Haplotipos , Migración Humana , Humanos , Datos de Secuencia Molecular , Dinámica Poblacional , Taiwán
11.
BMC Genet ; 15: 77, 2014 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-24965575

RESUMEN

BACKGROUND: Much of the data resolution of the haploid non-recombining Y chromosome (NRY) haplogroup O in East Asia are still rudimentary and could be an explanatory factor for current debates on the settlement history of Island Southeast Asia (ISEA). Here, 81 slowly evolving markers (mostly SNPs) and 17 Y-chromosomal short tandem repeats were used to achieve higher level molecular resolution. Our aim is to investigate if the distribution of NRY DNA variation in Taiwan and ISEA is consistent with a single pre-Neolithic expansion scenario from Southeast China to all ISEA, or if it better fits an expansion model from Taiwan (the OOT model), or whether a more complex history of settlement and dispersals throughout ISEA should be envisioned. RESULTS: We examined DNA samples from 1658 individuals from Vietnam, Thailand, Fujian, Taiwan (Han, plain tribes and 14 indigenous groups), the Philippines and Indonesia. While haplogroups O1a*-M119, O1a1*-P203, O1a2-M50 and O3a2-P201 follow a decreasing cline from Taiwan towards Western Indonesia, O2a1-M95/M88, O3a*-M324, O3a1c-IMS-JST002611 and O3a2c1a-M133 decline northward from Western Indonesia towards Taiwan. Compared to the Taiwan plain tribe minority groups the Taiwanese Austronesian speaking groups show little genetic paternal contribution from Han. They are also characterized by low Y-chromosome diversity, thus testifying for fast drift in these populations. However, in contrast to data provided from other regions of the genome, Y-chromosome gene diversity in Taiwan mountain tribes significantly increases from North to South. CONCLUSION: The geographic distribution and the diversity accumulated in the O1a*-M119, O1a1*-P203, O1a2-M50 and O3a2-P201 haplogroups on one hand, and in the O2a1-M95/M88, O3a*-M324, O3a1c-IMS-JST002611 and O3a2c1a-M133 haplogroups on the other, support a pincer model of dispersals and gene flow from the mainland to the islands which likely started during the late upper Paleolithic, 18,000 to 15,000 years ago. The branches of the pincer contributed separately to the paternal gene pool of the Philippines and conjointly to the gene pools of Madagascar and the Solomon Islands. The North to South increase in diversity found for Taiwanese Austronesian speaking groups contrasts with observations based on mitochondrial DNA, thus hinting to a differentiated demographic history of men and women in these populations.


Asunto(s)
Cromosomas Humanos Y/genética , Genética de Población , Haplotipos , Asia Sudoriental , Flujo Genético , Sitios Genéticos , Migración Humana , Humanos , Masculino , Repeticiones de Microsatélite , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Taiwán
13.
Int J Clin Pharmacol Ther ; 51(2): 114-9, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23073143

RESUMEN

OBJECTIVE: Sarpogrelate hydrochloride is a selective 5-hydroxytryptamine receptor subtype 2A (5HT(2A)) antagonist that blocks serotonin-induced platelet aggregation. The aim of this study was to compare the pharmacokinetics of sarpogrelate and its metabolite after dosing with a controlledrelease (CR) formulation or an immediaterelease (IR) formulation. METHODS: In this open-label, 2-period, 2-treatment crossover study, 36 healthy male subjects were evenly allocated to two groups in a sequence-randomized manner. In the first period, the first group received 100-mg sarpogrelate IR 3 times at a 6-h interval, and the second group received 300-mg sarpogrelate CR once. After a 7-day washout, the two groups switched their dosing schedule. Serial blood sampling was performed up to 24 hours after the first drug administration during each period. Plasma concentrations of sarpogrelate and its metabolite (M-1) were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods. RESULTS: There were no significant differences between two formulations in the pharmacokinetic properties in the time to reach maximum plasma concentration (C(max)) of sarpogrelate and its metabolite. The CR-to-IR geometric mean ratios, as measured by area under the plasma concentration-time curve (AUC) were 1.31 (90% confidence interval, 1.22 - 1.41) for sarpogrelate and 1.21 (1.14 - 1.29) for M-1. The C(max) was 0.98 (0.85 - 1.12) for sarpogrelate and 1.07 (0.96 - 1.19) for M-1. CONCLUSIONS: After the administration of sarpogrelate hydrochloride CR and IR formulations using the same daily dose, AUCs were slightly higher for the CR formulation than for the IR formulation for both sarpogrelate and its metabolite M-1, but the C(max) values were similar.


Asunto(s)
Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/farmacocinética , Succinatos/administración & dosificación , Succinatos/farmacocinética , Adulto , Análisis de Varianza , Área Bajo la Curva , Cromatografía Liquida/métodos , Estudios Cruzados , Preparaciones de Acción Retardada/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/sangre , Valores de Referencia , República de Corea , Succinatos/sangre , Espectrometría de Masas en Tándem/métodos , Adulto Joven
14.
Virol J ; 9: 133, 2012 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-22824586

RESUMEN

BACKGROUND: Virus subtype H13N2, A/mallard/Kr/SH38-45/2010 (H13N2), was first isolated from a mallard fecal sample in South Korea. RESULTS: Phylogenetic analysis of all eight viral genes revealed that this virus emerged by genetic mixing between Eurasian and North American gene pools, and possibly between wild ducks and gulls. The H13 and N2 surface genes clustered together in a group with Eurasian isolates from gulls and wild birds, respectively. The PB2, PA, NP, M and NS segments belonged to the Eurasian lineage, whereas the PB1 gene clustered in the North American lineage. Furthermore, they showed a bird-dependent pattern in phylogenetic analysis: the M gene was similar to subtype H13 viruses within gulls, whereas other segments were similar to avian influenza viruses of other subtypes from wild ducks. CONCLUSIONS: The data suggests that the novel reassortant H13N2 virus isolated in South Korea might have emerged by genetic reassortment between intercontinental and interspecies transmission in wild birds.


Asunto(s)
Anseriformes/virología , Heces/virología , Virus de la Influenza A/aislamiento & purificación , ARN Viral/genética , Virus Reordenados/aislamiento & purificación , Animales , Análisis por Conglomerados , Virus de la Influenza A/genética , Datos de Secuencia Molecular , Filogenia , Virus Reordenados/genética , República de Corea , Análisis de Secuencia de ADN , Proteínas Virales/genética
15.
Artículo en Inglés | MEDLINE | ID: mdl-23346193

RESUMEN

This study was designed to determine the therapeutic efficacy and safety of the Shi-cha capsule, a Chinese herbal formula, in the treatment of patients with wind-cold type common cold. In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with wind-cold type common cold received 0.6 g of Shi-cha capsule plus 0.6 g placebo (group A), 1.2 g of Shi-cha capsule (group B), or 1.2 g placebo (group C), three times daily for 3 days and followed up to 10 days. The primary end point was all symptom duration. The secondary end points were main symptom duration, minor symptom duration, the changes in cumulative symptom score, main symptom score, and minor symptom score 4 days after the treatment, as well as adverse events. A total of 377 patients were recruited and 360 met the inclusive criteria; 120 patients constituted each treatment group. Compared with patients in group C, patients in groups A and B had significant improvement in the all symptom duration, main symptom duration, minor symptom duration, as well as change from baseline of cumulative symptom score, main symptom score, and minor symptom score at day 4. The symptom durations and scores showed slight superiority of group B over group A, although these differences were not statistically significant. There were no differences in adverse events. The Shi-cha capsule is efficacious and safe for the treatment of patients with wind-cold type common cold. Larger trials are required to fully assess the benefits and safety of this treatment for common cold.

16.
Avian Dis ; 56(1): 218-23, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22545549

RESUMEN

A Newcastle disease surveillance program was conducted at live bird markets in Korea to expand our epidemiologic understanding of the disease in Korea. During the surveillance program, 10 lentogenic Newcastle disease viruses (NDVs) were isolated and identified from apparently healthy chickens and ducks at live bird markets. The lentogenic viruses had sequence motifs of either 112GKQGRL117 (n = 8) or 112GRQGRL117 (n = 2) at the F0 cleavage site. Sequencing and phylogenetic analyses of NDV isolates based on the hypervariable region of the F protein revealed two different genotypes: genotypes I (n = 8) and II (n = 2). Genotype I viruses were most closely related to the NDV V4 strain (n = 7) or the NDV Ulster 2C strain (n = 1). In contrast, genotype II viruses clustered with the NDV vaccine strains (LaSota and VG/GA) that are commonly used as live vaccines in Korea. The epidemiologic importance of NDV at live bird markets in Korea is discussed.


Asunto(s)
Pollos , Patos , Enfermedad de Newcastle/epidemiología , Virus de la Enfermedad de Newcastle/genética , ARN Viral/genética , Animales , Datos de Secuencia Molecular , Enfermedad de Newcastle/virología , Virus de la Enfermedad de Newcastle/clasificación , Virus de la Enfermedad de Newcastle/aislamiento & purificación , Filogenia , República de Corea/epidemiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
17.
Mol Diagn Ther ; 26(6): 679-688, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36125657

RESUMEN

BACKGROUND: The PD-L1 IHC 22C3 pharmDx used on the Dako Autostainer Link 48 (ASL48) staining platform is an established method for assessing programmed death-ligand 1 (PD-L1) expression in tumor tissue and determining patient eligibility for pembrolizumab treatment; however, the availability of this platform is limited in Europe and Asia. OBJECTIVES: The aims of this study were to develop and optimize protocols for the PD-L1 22C3 antibody concentrate with multiple immunohistochemistry staining platforms and to validate these protocols using PD-L1 combined positive score (CPS) with a cut-off of ≥ 1 in gastric or gastroesophageal junction adenocarcinoma. DESIGN: The 22C3 antibody concentrate was tested and optimized protocols were developed for use with three staining platforms: Dako ASL48, Ventana BenchMark ULTRA, and Leica BOND-MAX. Tumor specimens (N = 120) from patients with gastric or gastroesophageal junction adenocarcinoma were used for the validation study; these specimens were evaluated independently by three pathologists for PD-L1 CPS as a continuous variable and using a cut-off of ≥ 1. PD-L1 IHC 22C3 pharmDx used on the Dako ASL48 platform served as the reference or gold standard. RESULTS: The intraclass correlation coefficient of CPS as a continuous variable between the gold standard and each staining platform assessed was 0.910-0.989. When CPS was dichotomized based on a cut-off of ≥ 1, depending on the pathologist and the platform used, positive percentage agreement was 81-99% and negative percentage agreement was 90-100%. Interobserver agreement using the gold standard showed substantial agreement (κ = 0.779). CONCLUSION: The PD-L1 22C3 antibody concentrate can potentially be used with the laboratory-developed test on three commercially available immunohistochemistry staining platforms to determine PD-L1 expression in tumor samples from patients with gastric or gastroesophageal junction adenocarcinoma.


Asunto(s)
Adenocarcinoma , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/patología , Biomarcadores de Tumor/uso terapéutico , Unión Esofagogástrica/metabolismo , Unión Esofagogástrica/patología
18.
Mol Biol Evol ; 27(1): 21-31, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19755666

RESUMEN

Relatively little is known about the genetic diversity of the Philippine population, and this is an important gap in our understanding of Southeast Asian and Oceanic prehistory. Here we describe mitochondrial DNA (mtDNA) variation in 423 Philippine samples and analyze them in the context of the genetic diversity of other Southeast Asian populations. The majority of Philippine mtDNA types are shared with Taiwanese aboriginal groups and belong to haplogroups of postglacial and pre-Neolithic origin that have previously been identified in East Asian and Island Southeast Asian populations. Analysis of hypervariable segment I sequence variation within individual mtDNA haplogroups indicates a general decrease in the diversity of the most frequent types (B4a1a, E1a1a, and M7c3c) from the Taiwanese aborigines to the Philippines and Sulawesi, although calculated standard error measures overlap for these populations. This finding, together with the geographical distribution of ancestral and derived haplotypes of the B4a1a subclade including the Polynesian Motif, is consistent with southward dispersal of these lineages "Out of Taiwan" via the Philippines to Near Oceania and Polynesia. In addition to the mtDNA components shared with Taiwanese aborigines, complete sequence analyses revealed a minority of lineages in the Philippines that share their origins--possibly dating back to the Paleolithic--with haplogroups from Indonesia and New Guinea. Other rare lineages in the Philippines have no closely related types yet identified elsewhere.


Asunto(s)
Pueblo Asiatico/genética , ADN Mitocondrial/genética , Variación Genética , Geografía , Haplotipos , Humanos , Indonesia , Filipinas , Filogenia , Taiwán
19.
BMC Genet ; 12: 21, 2011 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-21281460

RESUMEN

BACKGROUND: Yami and Ivatan islanders are Austronesian speakers from Orchid Island and the Batanes archipelago that are located between Taiwan and the Philippines. The paternal genealogies of the Yami tribe from 1962 monograph of Wei and Liu were compared with our dataset of non-recombining Y (NRY) chromosomes from the corresponding families. Then mitochondrial DNA polymorphism was also analyzed to determine the matrilineal relationships between Yami, Ivatan, and other East Asian populations. RESULTS: The family relationships inferred from the NRY Phylogeny suggested a low number of paternal founders and agreed with the genealogy of Wei and Liu (P < 0.01). Except for one Y short tandem repeat lineage (Y-STR), seen in two unrelated Yami families, no other Y-STR lineages were shared between villages, whereas mtDNA haplotypes were indiscriminately distributed throughout Orchid Island. The genetic affinity seen between Yami and Taiwanese aborigines or between Ivatan and the Philippine people was closer than that between Yami and Ivatan, suggesting that the Orchid islanders were colonized separately by their nearest neighbors and bred in isolation. However a northward gene flow to Orchid Island from the Philippines was suspected as Yami and Ivatan peoples both speak Western Malayo-Polynesian languages which are not spoken in Taiwan. Actually, only very little gene flow was observed between Yami and Ivatan or between Yami and the Philippines as indicated by the sharing of mtDNA haplogroup B4a1a4 and one O1a1* Y-STR lineage. CONCLUSIONS: The NRY and mtDNA genetic information among Yami tribe peoples fitted well the patrilocal society model proposed by Wei and Liu. In this proposal, there were likely few genetic exchanges among Yami and the Philippine people. Trading activities may have contributed to the diffusion of Malayo-Polynesian languages among them. Finally, artifacts dating 4,000 YBP, found on Orchid Island and indicating association with the Out of Taiwan hypothesis might be related to a pioneering stage of settlement, as most dating estimates inferred from DNA variation in our data set ranged between 100-3,000 YBP.


Asunto(s)
Pueblo Asiatico/genética , ADN Mitocondrial , Asia Oriental , Femenino , Genealogía y Heráldica , Humanos , Masculino , Nativos de Hawái y Otras Islas del Pacífico , Filipinas/etnología , Filogenia , Polimorfismo Genético , Taiwán/etnología
20.
Virus Genes ; 42(1): 55-63, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20960044

RESUMEN

H1 avian influenza viruses (AIVs) isolated from migratory birds and domestic ducks from 2003 to 2007 were analyzed to determine their genetic relationship. Phylogenic analysis with nucleotide sequences of all eight gene segments showed that 13 H1 AIVs from migratory birds and domestic ducks belonged to Eurasian avian lineages and were closely related to each other. Compared with H1 influenza viruses of swine or human origin in Korea, there was no evidence of reassortment among the human, swine, and avian hosts. Our results show that H1 AIVs isolated in Korea from 2003 to 2007 were genetically stable. However, continued surveillance is needed considering the role of migratory birds and domestic duck as a source of AIVs.


Asunto(s)
Aves/virología , Patos/virología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Virus de la Influenza A/genética , Filogenia , Animales , Heces/virología , Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/virología , ARN Viral/genética , República de Corea , Análisis de Secuencia de ARN
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