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1.
Artigo em Inglês | MEDLINE | ID: mdl-32109631

RESUMO

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the CATCH-LIFE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n=2600 patients) and July 2018 through January 2019 (n=1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P=.04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared to patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P<.001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P<.001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension.

2.
J Transl Med ; 18(1): 40, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000807

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms. METHODS: GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein-protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan-Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. RESULTS: In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes. CONCLUSION: CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.

3.
Obstet Gynecol ; 132(6): 1421-1429, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30399093

RESUMO

OBJECTIVE: To develop an effective, low-cost, single-visit cervical screening strategy incorporating a modified Pap test and visual inspection with acetic acid and Lugol's iodine for low-income settings. METHODS: We conducted a prospective cohort trial. Two low-income Muslim Uyghur communities in China's far western Kashi Prefecture served as pilot and validation study sites, respectively, and 4,049 women (aged 30-59 years) were screened. The conventional Pap test was modified using a cotton swab to collect cervical cells without scraping the cervix using an Ayre spatula, allowing visual inspection with acetic acid (and visual inspection with Lugol's iodine if visual inspection with acetic acid was negative) to be performed in a single visit. Results from both tests were available within 1-2 hours. Women positive for either or both underwent same-day biopsy that was shipped by a courier service to a central pathology laboratory. RESULTS: Single-visit screening incorporating both a modified Pap test and visual inspection achieved a sensitivity of 96.0% (95% CI 91.6-100), which was superior to Pap testing (76%, 95% CI 66.3-85.7; P<.001) or visual inspection with acetic acid-visual inspection with Lugol's iodine (48%, 95% CI 36.7-59.3; P<.001) alone in detecting cervical intraepithelial neoplasia (CIN) 2 or worse lesions. Rapid interpretation of both diagnostic procedures facilitated efficient same-day biopsy that achieved a negative predictive value of 98.2% in detecting CIN 2 or worse lesions. The increased sensitivity and minimized loss of follow-up allowed this approach to identify an extremely high prevalence of CIN 1 (2,741/100,000, 95% CI 2,238-3,245/100,000), CIN 2 or 3 (1,457/100,000, 95% CI 1,088-1,826/100,000), and cervical cancer (395/100,000, 95% CI 202-589/100,000) among these underscreened, at-risk women. CONCLUSION: Single-visit cervical screening with both a modified Pap test and visual inspection has greater sensitivity to detect high-grade CINs, reduces loss of follow-up, and could be an efficient low-cost strategy for low-resource settings.


Assuntos
Neoplasia Intraepitelial Cervical/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias do Colo do Útero/diagnóstico , Ácido Acético , Adulto , Biópsia , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/patologia , China , Corantes , Detecção Precoce de Câncer/economia , Feminino , Exame Ginecológico , Humanos , Iodetos , Pessoa de Meia-Idade , Teste de Papanicolaou , Projetos Piloto , Áreas de Pobreza , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal
4.
J Dig Dis ; 19(10): 614-625, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30226019

RESUMO

OBJECTIVE: This research sought to verify whether acute-on-chronic liver failure (ACLF) develops in hepatitis B virus (HBV)-related cirrhotic patients with previous decompensation and to identify the similarity between assumed ACLF patients and those with ACLF that developed from compensated cirrhosis. METHODS: Patients with HBV-related cirrhosis were retrospectively screened and divided into the cirrhotic patients with first acute decompensation (AD) group and those with previous decompensation. Patients' characteristics, changes in laboratory results during hospitalization such as serum levels of total bilirubin (TB), creatinine (Cr) and white blood cell (WBC) counts, the Model for End-Stage Liver Disease (MELD) score and the 28-day and 1-year mortality rates were compared. RESULTS: Altogether 890 patients were enrolled and divided into the compensated cirrhotic group with first AD (n = 400; 157 of whom diagnosed as ACLF within 28 days after admission according to the European Association for the Study of the Liver-Chronic Liver Failure [EASL-CLIF] criteria) and those with previous decompensation (n = 490; of whom 143 met the ACLF criteria [assumed ACLF]). There was no significant difference in 28-day mortality between the assumed ACLF group with previous decompensation and ACLF group with first AD. The WBC count, TB and Cr levels, international normalized ratio and MELD score exhibited similar variations in both groups at days 1, 7 and 28; however, these values in both ACLF groups significantly differed from the non-ACLF group. CONCLUSION: HBV-related cirrhotic patients with previous decompensation who met the ACLF criteria had similar characteristic to ACLF patients with first AD.


Assuntos
Insuficiência Hepática Crônica Agudizada/etiologia , Hepatite B/complicações , Cirrose Hepática/complicações , Insuficiência Hepática Crônica Agudizada/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
5.
Am J Epidemiol ; 187(9): 1829-1839, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29762630

RESUMO

Definitions and descriptions of acute-on-chronic liver failure (ACLF) vary between Western and Eastern types, and alcoholism and hepatitis B virus (HBV) are, respectively, the main etiologies. To determine whether there are unified diagnostic criteria and common treatment programs for different etiologies of ACLF, a multicenter prospective cohort with the same inclusion criteria and disease indicators as those used in the European Consortium Acute-on-Chronic Liver Failure in Cirrhosis Study is urgently needed in Asia, where the prevalence of HBV is high. A multicenter prospective cohort of 2,600 patients was designed, drawing from 14 nationwide liver centers from tertiary university hospitals in China, and 2,600 hospitalized patients with chronic liver disease (both cirrhotic and noncirrhotic) of various etiologies with acute decompensation or acute hepatic injury were continuously recruited from January 2015 to December 2016. Data were collected during hospitalization, and follow-ups were performed once a month, with plans to follow all patients until 36 months after hospital discharge. Of these patients, 1,859 (71.5%) had HBV-related disease, 1,833 had cirrhotic disease, and 767 had noncirrhotic disease. The numbers and proportions of enrolled patients from each participating center and the baseline characteristics of the patients with or without cirrhosis are presented.


Assuntos
Insuficiência Hepática Crônica Agudizada/epidemiologia , Sistema de Registros , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Clin Exp Pharmacol Physiol ; 45(7): 675-682, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29575169

RESUMO

Synovial sarcoma (SS) is a mesenchymal malignant neoplasm showing characteristics of epithelial-mesenchymal biphasic differentiation. SS is of uncertain cellular origin; however, studies have suggested that SS originates from a somatic stem cell population. In this study, we aim to determine whether differential morphological features of the epithelial-mesenchymal transition (EMT) contributed to the tumourigenesis of SS invasion and metastasis. Twelve paraffin-embedded formalin-fixed tissue (FFPE) SS tissue specimens were obtained, and laser capture microdissection (LCM) with the ArcturusXT system and small chip method (SCM) were used to isolate and purify spindle and epithelial cells from SS specimens. The TRIzol method was used to extract RNA, and the mRNA levels of EMT-related genes in epithelial and spindle cells of SS specimens were measured using real-time fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results show that collection of about 2 × 104 cells from FFPE samples using LCM was sufficient for qRT-PCR, with an efficiency of 75%. Compared with LCM, 72.2% (13 of 18) RNA samples were successfully extracted using SCM to isolate cells from FFPE SS tissues. In the 16 samples (11 spindle cell samples and 5 epithelial cell samples), Snail mRNA was significantly upregulated in spindle cell areas compared with that in epithelial cell areas (P = .001). Expression levels of the epithelial marker E-cadherin and the mesenchymal marker N-cadherin were not significantly different between epithelial and spindle cell areas. In spindle cells of recurrent SS samples, the mRNA levels of E-cadherin, N-cadherin, Snail, and Slug were higher in primary SS samples than in recurrent samples. Taken together, our results indicated that in SS samples, Snail mRNA was upregulated in spindle cell areas compared with that in epithelial cell areas and that the expression of EMT-related genes was increased in primary SS. LCM could be used to isolate and purify RNA from FFPE samples.


Assuntos
Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Microdissecção e Captura a Laser , Sarcoma Sinovial/genética , Sarcoma Sinovial/patologia , Formaldeído , Humanos , Inclusão em Parafina , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Recidiva , Fixação de Tecidos
7.
J Dig Dis ; 18(5): 292-301, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28485081

RESUMO

OBJECTIVE: Acute-on-chronic liver failure (ACLF) is a distinct syndrome that develops in patients with cirrhosis and acute decompensation (AD). This study focused on the precipitating events (PEs) of hepatitis B virus (HBV)-related cirrhotic patients diagnosed as ACLF based on the Chronic Liver Failure Consortium organ failure (CLIF-C OF) score. METHODS: Hospitalized patients with HBV-related cirrhosis and AD were retrospectively included. The patients' characteristics, laboratory test results, PEs, CLIF-C OF score and short-term prognosis were evaluated. RESULTS: Of the 890 patients enrolled 300 (33.7%) were diagnosed as ACLF and 590 (66.3%) without ACLF. ACLF patients had a higher incidence of PEs than those without ACLF. The ACLF patients were more prone to having PEs of bacterial infection (P < 0.001), HBV reactivation (P < 0.001), active alcoholism (P = 0.036) and superimposed hepatitis virus infection (P = 0.031), whereas portal vein thrombosis (P = 0.002) were less common in the non-ACLF group. ACLF patients with the top four single PEs had diverse types of organ failures. However, they shared a similar short-term prognosis. While in patients without PEs the ACLF group had higher systemic inflammation and deterirated outcomes compared with the non-ACLF group. CONCLUSIONS: PEs of bacterial infection, HBV reactivation, active alcoholism and superimposed hepatitis virus infection, but not GI hemorrhage or portal vein thrombosis, were risk factors for ACLF. There may be two types of patients with ACLF based on the differences in the clinical manifestation of the disease.


Assuntos
Insuficiência Hepática Crônica Agudizada/etiologia , Hepatite B Crônica/complicações , Cirrose Hepática/complicações , Adulto , Alcoolismo/complicações , Infecções Bacterianas/complicações , Progressão da Doença , Feminino , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Ativação Viral
8.
Sci Rep ; 5: 14139, 2015 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-26420475

RESUMO

Of the two cultivated species of allopolyploid cotton, Gossypium barbadense produces extra-long fibers for the production of superior textiles. We sequenced its genome (AD)2 and performed a comparative analysis. We identified three bursts of retrotransposons from 20 million years ago (Mya) and a genome-wide uneven pseudogenization peak at 11-20 Mya, which likely contributed to genomic divergences. Among the 2,483 genes preferentially expressed in fiber, a cell elongation regulator, PRE1, is strikingly At biased and fiber specific, echoing the A-genome origin of spinnable fiber. The expansion of the PRE members implies a genetic factor that underlies fiber elongation. Mature cotton fiber consists of nearly pure cellulose. G. barbadense and G. hirsutum contain 29 and 30 cellulose synthase (CesA) genes, respectively; whereas most of these genes (>25) are expressed in fiber, genes for secondary cell wall biosynthesis exhibited a delayed and higher degree of up-regulation in G. barbadense compared with G. hirsutum, conferring an extended elongation stage and highly active secondary wall deposition during extra-long fiber development. The rapid diversification of sesquiterpene synthase genes in the gossypol pathway exemplifies the chemical diversity of lineage-specific secondary metabolites. The G. barbadense genome advances our understanding of allopolyploidy, which will help improve cotton fiber quality.


Assuntos
Evolução Biológica , Fibra de Algodão , Genoma de Planta , Genômica , Gossypium/genética , Gossypium/metabolismo , Metabolômica , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Cromossomos de Plantas , Análise por Conglomerados , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Estudos de Associação Genética , Genômica/métodos , Metabolômica/métodos , Anotação de Sequência Molecular , Fenótipo , Filogenia , Poliploidia , Característica Quantitativa Herdável , Sesquiterpenos/metabolismo , Translocação Genética
9.
EBioMedicine ; 2(6): 583-90, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26288819

RESUMO

Air pollution has been classified as Group 1 carcinogenic to humans, but the underlying tumorigenesis remains unclear. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China attributed to severe air pollution generated by combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis of air pollution. Here we analyzed the somatic mutations of 164 non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used. Whole genome sequencing revealed a mean of 289 somatic exonic mutations per tumor and the frequent C:G â†’ A:T nucleotide substitutions in Xuanwei NSCLCs. Exome sequencing of 2010 genes showed that Xuanwei and CR NSCLCs had a mean of 68 and 22 mutated genes per tumor, respectively (p < 0.0001). We found 167 genes (including TP53, RYR2, KRAS, CACNA1E) which had significantly higher mutation frequencies in Xuanwei than CR patients, and mutations in most genes in Xuanwei NSCLCs differed from those in CR cases. The mutation rates of 70 genes (e.g., RYR2, MYH3, GPR144, CACNA1E) were associated with patients' lifetime benzo(a)pyrene exposure. This study uncovers the mutation spectrum of air pollution-related lung cancers, and provides evidence for pollution exposure-genomic mutation relationship at a large scale.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Benzo(a)pireno/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Idoso , Sequência de Bases , Carcinoma Pulmonar de Células não Pequenas/induzido quimicamente , Transformação Celular Neoplásica , Carvão Mineral/efeitos adversos , Exposição Ambiental/efeitos adversos , Feminino , Frequência do Gene/genética , Genoma/genética , Humanos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Mutação/genética , Taxa de Mutação , Análise de Sequência de DNA , Fumaça/efeitos adversos
10.
Gene ; 530(2): 315-22, 2013 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-23981775

RESUMO

Although recent genome-wide association studies of esophageal squamous cell carcinoma (ESCC) identified a susceptibility locus in phospholipase C epsilon 1 (PLCE1) in Chinese Han populations, few studies further confirmed these findings in pure Kazakh population in which there are higher incidence and mortality of ESCC. Here, we investigated the potential associations between 19 SNPs of PLCE1 and susceptibility to ESCC in 222 cases and 326 controls from a pure ethnic population of Kazakh. Real-time PCR and immunohistochemistry were performed to detect the PLCE1 expression levels and evaluate their association with PLCE1 polymorphism. We found that only 4 SNPs (rs753724, rs11187842, rs2274223, and rs12263737) with moderate linkage disequilibrium (LD) confer significantly increased risk of ESCC, with the ORs ranging from 1.43 to 2.04, and there was a risk allele dose-dependent increase in ESCC risk (P-trend=0.043). Especially, the risk effects of rs2274223 were more evident in poor differentiation and advanced clinical stages of Kazakh ESCC. Additionally, the significantly lowest PLCE1 mRNA expression was found in the KYSE-150 cell line having no risk alleles compared with other three cell lines having risk alleles, and the normal tissues of both homozygous mutant type of PLCE1 rs12263737 and rs2274223 had a higher PLCE1 staining score than that of homozygous wild type. Our findings suggested that genetic variants in PLCE1 might serve as candidate markers for Kazakh ESCC susceptibility, and these LD variants might influence ESCC risk individually and jointly by promoting the messenger RNA and protein expression of the gene.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Expressão Gênica , Predisposição Genética para Doença , Fosfoinositídeo Fosfolipase C/genética , Polimorfismo Genético , Idoso , Alelos , Carcinoma de Células Escamosas/etnologia , Estudos de Casos e Controles , Linhagem Celular , China/epidemiologia , Neoplasias Esofágicas/etnologia , Feminino , Frequência do Gene , Humanos , Cazaquistão/etnologia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Risco
11.
APMIS ; 121(10): 908-18, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23659763

RESUMO

Three recent large-scale genome-wide association studies (GWAS) in Chinese Han populations have identified an esophageal squamous cell carcinoma (ESCC) susceptibility locus within phospholipase C epsilon 1 (PLCE1) gene, which encodes a phospholipase involved in intracellular signaling. The expressed PLCE1 in ESCC, however, are inconsistent. This study examined PLCE1 expression by immunohistochemistry (IHC) from 110 ethnic Kazakh ESCC patients and 50 from adjacent normal esophageal tissues (NETs). The expressed PLCE1 was localized in cytoplasm, especially in the peripheral layers of cancer cell nests, which was significantly higher in tumors than in NETs (p < 0.001). Increased expression of PLCE1 was correlated with advanced tumor-node-metastasis (TNM) stages (p = 0.015) and lymph node metastasis (p = 0.003) in patients with ESCC. Of the 110 patients, we examined 50 paired ESCC tissues and corresponding NETs by quantitative RT-PCR (polymerase chain reaction) and the mean mRNA level of PLCE1 in ESCC was 1.85-fold higher compared with those in corresponding NETs (p = 0.0012). Meanwhile, 4 of 5 ESCC cell lines also showed elevated expression of PLCE1 mRNA. Furthermore, elevated expression of PLCE1 mRNA in Kazakh ESCC was associated with its immunoreactivity (ρ = 0.297, p = 0.040), lymph node metastasis (p < 0.001), and advanced TNM stages of ESCC (p = 0.013). To our knowledge, this study demonstrates for the first time that PLCE1 overexpression correlates with lymph node metastasis and advanced TNM stages of Kazakh ESCC, implicating a role of PLCE1 in cancer metastasis and aggressiveness in ethnic Kazakh patients with ESCC. Furthermore, the current findings may warrant investigations into whether inhibiting PLCE1 could be a strategy for targeted anticancer therapy particularly for Kazakh ESCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Fosfoinositídeo Fosfolipase C/genética , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , China/epidemiologia , Neoplasias Esofágicas/etnologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Esôfago , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Cazaquistão/etnologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico
12.
Mol Cell Biol ; 25(19): 8643-55, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16166644

RESUMO

By establishing mouse primary keratinocytes (KCs) in culture, we were able, for the first time, to express papillomavirus major capsid (L1) proteins by transient transfection of authentic or codon-modified L1 gene expression plasmids. We demonstrate in vitro and in vivo that gene codon composition is in part responsible for differentiation-dependent expression of L1 protein in KCs. L1 mRNA was present in similar amounts in differentiated and undifferentiated KCs transfected with authentic or codon-modified L1 genes and had a similar half-life, demonstrating that L1 protein production is posttranscriptionally regulated. We demonstrate further that KCs substantially change their tRNA profiles upon differentiation. Aminoacyl-tRNAs from differentiated KCs but not undifferentiated KCs enhanced the translation of authentic L1 mRNA, suggesting that differentiation-associated change to tRNA profiles enhances L1 expression in differentiated KCs. Thus, our data reveal a novel mechanism for regulation of gene expression utilized by a virus to direct viral capsid protein expression to the site of virion assembly in mature KCs. Analysis of two structural proteins of KCs, involucrin and keratin 14, suggests that translation of their mRNAs is also regulated, in association with KC differentiation in vitro, by a similar mechanism.


Assuntos
Capsídeo/química , Códon , Regulação Viral da Expressão Gênica , Queratinócitos/citologia , Queratinócitos/virologia , Vírus/metabolismo , Animais , Biolística , Northern Blotting , Western Blotting , Diferenciação Celular , Células Cultivadas , Cromatografia Líquida de Alta Pressão , DNA/metabolismo , Dactinomicina/farmacologia , Técnicas In Vitro , Queratina-14 , Queratinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Hibridização de Ácido Nucleico , Papillomaviridae/genética , Plasmídeos/metabolismo , Biossíntese de Proteínas , Precursores de Proteínas/metabolismo , RNA/metabolismo , RNA Mensageiro/metabolismo , RNA de Transferência/química , RNA de Transferência/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Transfecção
13.
Genome Res ; 15(6): 757-67, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15899963

RESUMO

Xanthomonas campestris pathovar campestris (Xcc) is the causative agent of crucifer black rot disease, which causes severe losses in agricultural yield world-wide. This bacterium is a model organism for studying plant-bacteria interactions. We sequenced the complete genome of Xcc 8004 (5,148,708 bp), which is highly conserved relative to that of Xcc ATCC 33913. Comparative genomics analysis indicated that, in addition to a significant genomic-scale rearrangement cross the replication axis between two IS1478 elements, loss and acquisition of blocks of genes, rather than point mutations, constitute the main genetic variation between the two Xcc strains. Screening of a high-density transposon insertional mutant library (16,512 clones) of Xcc 8004 against a host plant (Brassica oleraceae) identified 75 nonredundant, single-copy insertions in protein-coding sequences (CDSs) and intergenic regions. In addition to known virulence factors, full virulence was found to require several additional metabolic pathways and regulatory systems, such as fatty acid degradation, type IV secretion system, cell signaling, and amino acids and nucleotide metabolism. Among the identified pathogenicity-related genes, three of unknown function were found in Xcc 8004-specific chromosomal segments, revealing a direct correlation between genomic dynamics and Xcc virulence. The present combination of comparative and functional genomic analyses provides valuable information about the genetic basis of Xcc pathogenicity, which may offer novel insight toward the development of efficient methods for prevention of this important plant disease.


Assuntos
Proteínas de Bactérias/genética , Genoma Bacteriano , Fatores de Virulência/genética , Xanthomonas campestris/genética , Xanthomonas campestris/patogenicidade , Brassica/genética , Brassica/microbiologia , Elementos de DNA Transponíveis , Dados de Sequência Molecular , Mutagênese Insercional , Regiões Operadoras Genéticas , Doenças das Plantas/genética , Análise de Sequência de DNA
14.
Nature ; 422(6934): 888-93, 2003 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-12712204

RESUMO

Leptospirosis is a widely spread disease of global concern. Infection causes flu-like episodes with frequent severe renal and hepatic damage, such as haemorrhage and jaundice. In more severe cases, massive pulmonary haemorrhages, including fatal sudden haemoptysis, can occur. Here we report the complete genomic sequence of a representative virulent serovar type strain (Lai) of Leptospira interrogans serogroup Icterohaemorrhagiae consisting of a 4.33-megabase large chromosome and a 359-kilobase small chromosome, with a total of 4,768 predicted genes. In terms of the genetic determinants of physiological characteristics, the facultatively parasitic L. interrogans differs extensively from two other strictly parasitic pathogenic spirochaetes, Treponema pallidum and Borrelia burgdorferi, although similarities exist in the genes that govern their unique morphological features. A comprehensive analysis of the L. interrogans genes for chemotaxis/motility and lipopolysaccharide synthesis provides a basis for in-depth studies of virulence and pathogenesis. The discovery of a series of genes possibly related to adhesion, invasion and the haematological changes that characterize leptospirosis has provided clues about how an environmental organism might evolve into an important human pathogen.


Assuntos
Genes Bacterianos/genética , Genoma Bacteriano , Leptospira interrogans/genética , Leptospira interrogans/patogenicidade , Aderência Bacteriana/genética , Quimiotaxia , Cromossomos Bacterianos/genética , Humanos , Leptospira interrogans/citologia , Leptospira interrogans/metabolismo , Lipopolissacarídeos/biossíntese , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Virulência/genética
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