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1.
Medicine (Baltimore) ; 98(38): e16991, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567936

RESUMO

BACKGROUND: Interleukin 12 (IL-12) and interleukin 12 receptor (IL12R), key inflammatory cytokines in the immune system, participate in bridging the innate immunity and adaptive immunity. No previous work has reported the role of IL-12 and IL12R in high-risk human papillomavirus (hrHPV) susceptibility. The purpose of this study was to investigate the association of IL-12, IL12R polymorphisms, and serum IL-12 levels with hrHPV susceptibility in rural women from Luohe, Henan, China. METHODS: Two hundred sixty cases with hrHPV infection and 260 healthy controls were selected. Enzyme-linked immunosorbent assays were used to detect the serum IL-12 levels, and the polymorphisms of IL12B rs3212227, IL12RB1 rs393548, and IL12RB1 rs436857 were determined using DNA sequencing. RESULTS: The serum IL-12 levels were significantly lower in cases with hrHPV infection compared with those in healthy controls (P < .01).There was no significant difference in IL12 rs3212227, IL12RB1rs436857, and IL12RB1rs393548 genotype and allele frequencies between cases and controls (P > .05). Furthermore, with respect to the IL12 rs3212227 polymorphism with serum IL-12 levels, although serum IL-12 levels were lower in cases than in controls, we did not find any differences between serum IL-12 levels and genotypes in cases(P > .05). CONCLUSIONS: Our data demonstrates that low serum IL-12 levels may be associated with hrHPV susceptibility but are not associated with IL-12 gene polymorphisms; furthermore, IL-12 and IL12R gene polymorphisms may not contribute susceptibility to hrHPV in rural women from Luohe, Henan, China.


Assuntos
Predisposição Genética para Doença , Subunidade p40 da Interleucina-12/genética , Infecções por Papillomavirus/genética , Receptores de Interleucina-12/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Subunidade p40 da Interleucina-12/sangue , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-12/sangue , População Rural
2.
Medicine (Baltimore) ; 98(38): e17224, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567981

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a common autoimmune disease of the central nervous system (CNS), and is associated with genetic factors. FOXP3 gene polymorphism has been reported as the risk factor for MS, however, previous studies have showed conflicting results. The purpose of this study is to investigate the association between FOXP3 gene polymorphism and the susceptibility to MS. METHODS: Pubmed, Embase, library of Cochrane, and Web of Science were used to search the eligible articles from January 1980 up to October 2018. The odds ratio (ORs) and its 95% confidence intervals (CI) were used to evaluate the strength of association. Allele model, homozygote model, heterozygote model, dominant model, and recessive model were used to evaluate the association between FOXP3 gene polymorphism and MS. RESULTS: A total of 5 studies contained 1276 MS patients and 1447 controls (for rs3761548) and 600 MS patients and 640 controls (for rs2232365) were enrolled in this meta-analysis. The association showed significant differences in allele and dominant model for rs3761548 polymorphism. In addition, a clear tendency to significance was detected in homozygote and recessive model for rs3761548 (P = .052). Subgroup analysis indicated a significant risk of MS in all genotype models but heterozygotes in Asians. CONCLUSION: FOXP3 gene polymorphism rs3761548 was associated with a higher MS risk, especially in Asians. This conclusion needs to be validated in more large samples and multiracial studies. LEVEL OF EVIDENCE: Level III diagnostic study.


Assuntos
Fatores de Transcrição Forkhead/genética , Predisposição Genética para Doença/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética , Genes/genética , Humanos , Esclerose Múltipla/etiologia
3.
Medicine (Baltimore) ; 98(38): e17225, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567982

RESUMO

The present study is to analyze the difference of gene methylation in early cervical adenocarcinoma and to find molecular markers for predicting the occurrence and development of cervical adenocarcinoma.A total of 15 cases of primary cervical adenocarcinoma and 10 cases of primary cervical squamous cell carcinoma at stages IB1 or IIA1 were included in the study. Infinium MethylationEPIC BeadChip (850K) was used to screen specifically expressed genes in cervical adenocarcinoma tissues. Bisulfite sequencing polymerase chain reaction (BSP) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to verify the methylation levels in cervical adenocarcinoma, cervical squamous cell carcinoma, and normal cervical tissues.Sex determining region Y-box 1 (SOX1) and cyclin D1 (CCND1) genes participated in multiple signaling pathways, being the central nodes of gene regulatory networks. SOX1 gene, but not CCND1 gene, was a specifically methylated gene in cervical adenocarcinoma according to BSP. According to qRT-PCR, methylation level of SOX1 in cervical adenocarcinoma tissues is significantly different from that in cervical squamous cell carcinoma tissues or normal cervical tissues, and the methylation level of CCND1 in cervical adenocarcinoma tissues or cervical squamous cell carcinoma tissues is significantly different from that in normal cervical tissues.The present study demonstrates that tumor-suppressor gene SOX1 is a methylation-specific expression gene of cervical adenocarcinoma and is expected to become a specific molecular marker for the diagnosis of cervical adenocarcinoma. However, CCND1 gene was not proven to be a specific methylation expression gene in cervical adenocarcinoma in the present study.


Assuntos
Adenocarcinoma/genética , Metilação de DNA/genética , Fatores de Transcrição SOXB1/genética , Neoplasias do Colo do Útero/genética , Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Colo do Útero/metabolismo , Ciclina D1/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , Marcadores Genéticos/genética , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias do Colo do Útero/metabolismo
4.
Water Sci Technol ; 80(3): 551-562, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31596266

RESUMO

Exposure to antibiotics, biocides, chemical preservatives, and heavy metals in different settings such as wastewater treatment plants (WWTPs) may apply selective pressure resulting in the enrichment of multiple resistant, co- and cross-resistant strains of bacteria. The purpose of this study was to identify and characterize potentially pathogenic triclosan (TCS) - and/or, chloroxylenol (PCMX) tolerant bacteria from sewage and river water in the North-West, Potchefstroom, South Africa. Several potential pathogens were identified, with Aeromonas isolates being most abundant. Clonal relationships between Aeromonas isolates found at various sampling points were elucidated using ERIC-PCR. Selected isolates were characterized for their minimum inhibitory concentrations against the biocides, as well as antibiotic resistance profiles, followed by an evaluation of synergistic and antagonistic interactions between various antimicrobials. Isolates were also screened for the presence of extracellular enzymes associated with virulence. High-performance liquid chromatography revealed the presence of both biocides in the wastewater, but fingerprinting methods did not reveal whether the WWTP is the source from which these organisms enter the environment. Isolates exhibited various levels of resistance to antimicrobials as well as several occurrences of synergy and antagonisms between the biocides and select antibiotics. Several isolates had a very high potential for virulence but further study is required to identify the specific virulence and resistance genes associated with the isolates in question.


Assuntos
Desinfetantes , Eliminação de Resíduos Líquidos , Águas Residuárias/microbiologia , Antibacterianos , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Rios , Esgotos , África do Sul
5.
Anticancer Res ; 39(10): 5525-5530, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570446

RESUMO

BACKGROUND/AIM: Basal cell carcinoma (BCC) has been genetically associated with an increased expression of angiotensin-converting enzyme (ACE), an important factor of the renin-angiotensin system which produces vasoconstrictor angiotensin II. Other factors of this system include angiotensinogen (AGT) and angiotensin receptors AGTR1, AGTR2. We investigated the possible association of BCC with genetic variability in the AGT, AGTR1 and AGTR2 genes. MATERIALS AND METHODS: DNA samples of 190 Greeks were studied, including 91 patients with BCC and 99 matched healthy controls. Molecular genotyping of patients and controls was performed for the polymorphisms AGT M235T, AGTR1 A1166C and AGTR2 G1675A. RESULTS: The mutant T allele that increases AGT gene expression was detected in two-fold increased frequency in BCC patients in comparison to healthy controls (p <0.001). On the contrary, no significant difference was observed in AGTR1 and AGTR2 variants between patients and controls. CONCLUSION: Increased expression of AGT may be associated with BCC.


Assuntos
Carcinoma Basocelular/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Angiotensinogênio/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/genética
6.
Anticancer Res ; 39(10): 5573-5579, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570452

RESUMO

BACKGROUND/AIM: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer, frequently infected with Merkel cell polyomavirus (MCPyV). H3K27me3 acts as a repressive histone modification that epigenetically controls gene transcription. The aim of this study was to examine H3K27me3 expression in MCC. MATERIALS AND METHODS: H3K27me3 expression levels were immunohistochemically analyzed in 20 MCPyV-positive MCCs, 15 MCPyV-negative MCCs with squamous cell carcinoma (SCC) (combined MCCs), and six MCPyV-negative pure MCCs. RESULTS: Reduced H3K27me3 expression was variously observed in MCCs. H3K27me3 H-score was significantly lower in MCPyV-negative MCCs than in MCPyV-positive MCCs (p=0.002). H3K27me3 expression was significantly lower in MCPyV-negative combined MCC component than in MCPyV-positive MCCs (p<0.001), MCPyV-negative pure MCCs (p=0.036), or pure MCC histology (p<0.001). Kaplan-Meier analysis showed no association of H3K27me3 with outcome. CONCLUSION: Differential reduction in H3K27me3 expression was observed based on MCPyV status and morphological type. These results implicate H3K27me3-mediated epigenetic changes in tumorigenesis of MCC, especially in MCPyV-negative MCC combined with SCC.


Assuntos
Carcinoma de Célula de Merkel/genética , Carcinoma de Células Escamosas/genética , Histonas/genética , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/genética , Carcinoma de Célula de Merkel/virologia , Carcinoma de Células Escamosas/virologia , Epigênese Genética/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Poliomavírus das Células de Merkel/patogenicidade , Pessoa de Meia-Idade , Infecções por Polyomavirus/genética , Infecções por Polyomavirus/virologia , Neoplasias Cutâneas/virologia , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/virologia
7.
Anticancer Res ; 39(10): 5623-5630, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570459

RESUMO

BACKGROUND: This study aimed to investigate p16 and COX2 expression in oropharyngeal squamous cell carcinoma (OPSCC), and evaluate the prognostic role of COX2 expression under the new TNM classification. MATERIALS AND METHODS: Biopsy specimens obtained from 75 patients with OPSCC were stained for p16 and COX2 expression immunohistochemically. The results and clinical records were analyzed retrospectively. RESULTS: Fifty-nine patients (79%) were positive for p16. COX2 expression was correlated with poor relapse-free survival in patients overall, and in p16-positive patients. Smoking was positively associated with COX2 expression. Moreover, both positive COX2 expression and anterior wall tumor subsite were independently correlated with lymph node metastasis, which was the only independent prognostic factor in p16-positive OPSCC. CONCLUSION: The p16-positive rate in this study was comparable with that in the USA and Europe, and higher than that in other Asian countries. COX2 expression might affect the prognosis of p16-positive OPSCC through promoting lymph node metastasis.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Metástase Linfática/genética , Metástase Linfática/patologia , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Ciclo-Oxigenase 2/genética , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
8.
J Chem Phys ; 151(12): 125101, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575173

RESUMO

Gene regulation is one of the most important fundamental biological processes in living cells. It involves multiple protein molecules that locate specific sites on DNA and assemble gene initiation or gene repression multimolecular complexes. While the protein search dynamics for DNA targets has been intensively investigated, the role of intermolecular interactions during the genetic activation or repression remains not well quantified. Here, we present a simple one-dimensional model of target search for two interacting molecules that can reversibly form a dimer molecular complex, which also participates in the search process. In addition, the proteins have finite residence times on specific target sites, and the gene is activated or repressed when both proteins are simultaneously present at the target. The model is analyzed using first-passage analytical calculations and Monte Carlo computer simulations. It is shown that the search dynamics exhibit a complex behavior depending on the strength of intermolecular interactions and on the target residence times. We also found that the search time shows a nonmonotonic behavior as a function of the dissociation rate for the molecular complex. Physical-chemical arguments to explain these observations are presented. Our theoretical approach highlights the importance of molecular interactions in the complex process of gene activation/repression by multiple transcription factor proteins.


Assuntos
DNA/química , Modelos Químicos , Simulação por Computador , DNA/genética , DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Cinética , Método de Monte Carlo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
9.
Adv Exp Med Biol ; 1164: 119-139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576545

RESUMO

Alternative splicing, the process of removing introns and joining exons of pre-mRNA, is critical for growth, development, tissue homeostasis, and species diversity. Dysregulation of alternative splicing can initiate and drive disease. Aberrant alternative splicing has been shown to promote the "hallmarks of cancer" in both hematological and solid cancers. Of interest, recent work has focused on the role of alternative splicing in prostate cancer and prostate cancer health disparities. We will provide a review of prostate cancer health disparities involving the African American population, alternative RNA splicing, and alternative splicing in prostate cancer. Lastly, we will summarize our work on differential alternative splicing in prostate cancer disparities and its implications for disparate health outcomes and therapeutic targets.


Assuntos
Processamento Alternativo , Resistência a Medicamentos , Disparidades nos Níveis de Saúde , Neoplasias da Próstata , Afro-Americanos/estatística & dados numéricos , Processamento Alternativo/genética , Resistência a Medicamentos/genética , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/fisiopatologia
10.
Mem Inst Oswaldo Cruz ; 114: e190149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576902

RESUMO

Human polycystic echinococcosis is a parasitic infection caused by the larval stage of Echinococcus vogeli, which occurs in rural areas of Central and South America. Until now, little information on the genetic variability of E. vogeli is available. Here, 32 samples from human-excised E. vogeli cysts had a 396-bp sequence of the mitochondrial cytochrome oxidase I (COI) gene sequenced and compared to another 17 COI sequences representing nine Echinococcus species. A Bayesian COI tree revealed that all E. vogeli sequences formed a monophyletic and well-supported clade with an E. vogeli reference sequence. The occurrence of geographically restricted E. vogeli COI haplotypes suggests retention of ancestral polymorphisms with little migration in Acre, Brazil.


Assuntos
Echinococcus/genética , Variação Genética/genética , Animais , Teorema de Bayes , Brasil , Equinococose/parasitologia , Echinococcus/isolamento & purificação , Haplótipos , Humanos
11.
Mem Inst Oswaldo Cruz ; 114: e190184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576903

RESUMO

American visceral leishmaniasis (AVL) has two main scenarios of transmission as follows: scattered cases in rural areas and urban outbreaks. Urban AVL is in active dispersion from the northeastern border of Argentina-Paraguay-Brazil to the South. The presence of Lutzomyia longipalpis was initially reported in urban environments in the northwestern border of the country. The presence of Lu. longipalpis, environmental variables associated with its distribution, and its genetic diversity were assessed in Salvador Mazza, Argentina, on the border with Bolivia. The genetic analysis showed high haplotype diversity, low nucleotide diversity, and low nucleotide polymorphism index. We discuss the hypothesis of an expanding urban population with introgressive hybridisation of older haplogroups found in their path in natural forest or rural environments, acquiring a new adaptability to urban environments, and the possibility of changes in vector capacity.


Assuntos
Distribuição Animal , Variação Genética/genética , Insetos Vetores/genética , Psychodidae/genética , Animais , Argentina , Bolívia , Brasil , DNA Mitocondrial/genética , Genes de Insetos/genética , Haplótipos , Insetos Vetores/classificação , Leishmaniose Cutânea/transmissão , Masculino , Filogeografia , Psychodidae/classificação
12.
Microb Cell Fact ; 18(1): 162, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581942

RESUMO

BACKGROUND: Efficient and convenient genome-editing toolkits can expedite genomic research and strain improvement for desirable phenotypes. Zymomonas mobilis is a highly efficient ethanol-producing bacterium with a small genome size and desirable industrial characteristics, which makes it a promising chassis for biorefinery and synthetic biology studies. While classical techniques for genetic manipulation are available for Z. mobilis, efficient genetic engineering toolkits enabling rapidly systematic and high-throughput genome editing in Z. mobilis are still lacking. RESULTS: Using Cas12a (Cpf1) from Francisella novicida, a recombinant strain with inducible cas12a expression for genome editing was constructed in Z. mobilis ZM4, which can be used to mediate RNA-guided DNA cleavage at targeted genomic loci. gRNAs were then designed targeting the replicons of native plasmids of ZM4 with about 100% curing efficiency for three native plasmids. In addition, CRISPR-Cas12a recombineering was used to promote gene deletion and insertion in one step efficiently and precisely with efficiency up to 90%. Combined with single-stranded DNA (ssDNA), CRISPR-Cas12a system was also applied to introduce minor nucleotide modification precisely into the genome with high fidelity. Furthermore, the CRISPR-Cas12a system was employed to introduce a heterologous lactate dehydrogenase into Z. mobilis with a recombinant lactate-producing strain constructed. CONCLUSIONS: This study applied CRISPR-Cas12a in Z. mobilis and established a genome editing tool for efficient and convenient genome engineering in Z. mobilis including plasmid curing, gene deletion and insertion, as well as nucleotide substitution, which can also be employed for metabolic engineering to help divert the carbon flux from ethanol production to other products such as lactate demonstrated in this work. The CRISPR-Cas12a system established in this study thus provides a versatile and powerful genome-editing tool in Z. mobilis for functional genomic research, strain improvement, as well as synthetic microbial chassis development for economic biochemical production.


Assuntos
Edição de Genes/métodos , Genoma Bacteriano , Zymomonas/genética , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Endonucleases/metabolismo , Francisella/enzimologia , Plasmídeos/genética , Plasmídeos/metabolismo , RNA Guia/genética , RNA Guia/metabolismo , Zymomonas/metabolismo
13.
Microb Cell Fact ; 18(1): 163, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581944

RESUMO

BACKGROUND: Sustainable production of microbial fatty acids derivatives has the potential to replace petroleum based equivalents in the chemical, cosmetic and pharmaceutical industry. Most fatty acid sources for production oleochemicals are currently plant derived. However, utilization of these crops are associated with land use change and food competition. Microbial oils could be an alternative source of fatty acids, which circumvents the issue with agricultural competition. RESULTS: In this study, we generated a chimeric microbial production system that features aspects of both prokaryotic and eukaryotic fatty acid biosynthetic pathways targeted towards the generation of long chain fatty acids. We redirected the type-II fatty acid biosynthetic pathway of Escherichia coli BL21 (DE3) strain by incorporating two homologues of the beta-ketoacyl-[acyl carrier protein] synthase I and II from the chloroplastic fatty acid biosynthetic pathway of Arabidopsis thaliana. The microbial clones harboring the heterologous pathway yielded 292 mg/g and 220 mg/g DCW for KAS I and KAS II harboring plasmids respectively. Surprisingly, beta-ketoacyl synthases KASI/II isolated from A. thaliana showed compatibility with the FAB pathway in E. coli. CONCLUSION: The efficiency of the heterologous plant enzymes supersedes the overexpression of the native enzyme in the E. coli production system, which leads to cell death in fabF overexpression and fabB deletion mutants. The utilization of our plasmid based system would allow generation of plant like fatty acids in E. coli and their subsequent chemical or enzymatic conversion to high end oleochemical products.


Assuntos
Arabidopsis/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/biossíntese , Engenharia Metabólica , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/síntese química , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/genética , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Arabidopsis/enzimologia , Proteínas de Arabidopsis/síntese química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Vias Biossintéticas , Escherichia coli/enzimologia , Proteínas de Escherichia coli/genética , Ácido Graxo Sintases/genética , Ácidos Graxos/química , Isoenzimas/síntese química , Isoenzimas/genética , Isoenzimas/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo
14.
Med Clin North Am ; 103(6): 1005-1019, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582001

RESUMO

Heritable thoracic aortic disease (HTAD) can have life-threatening consequences if not diagnosed early. Affected individuals and at-risk family members benefit from both cardiology and genetic evaluations, including genetic testing. Important information can be obtained through family history, medical history, and genetic testing to help guide management and assess risk. A genetic diagnosis can guide cardiovascular management (type and frequency of vascular imaging, timing of surgical intervention), risk assessment for arterial aneurysm/dissection, evaluation of nonvascular features, and familial testing.


Assuntos
Aorta Torácica/anormalidades , Doenças da Aorta , Testes Genéticos/métodos , Administração dos Cuidados ao Paciente/métodos , Doenças da Aorta/genética , Doenças da Aorta/terapia , Humanos , Medicina de Precisão/métodos
15.
Med Clin North Am ; 103(6): 1021-1033, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582002

RESUMO

Joint hypermobility may be syndromic or nonsyndromic, asymptomatic or symptomatic. However, asymptomatic joint hypermobility can cause repetitive use injury, alter biomechanics, or become symptomatic later in life. Symptomatic joint hypermobility can result from soft tissue injury or muscular strain caused by muscular imbalance. Treatment is straightforward once joint hypermobility is recognized. Generalized joint hypermobility can be assessed using a standardized in-office examination. Generalized joint hypermobility may also be a feature of a heritable connective tissue disorder with other systemic findings. Therefore, assessing joint hypermobility in the context of musculoskeletal complaints may lead to recognizing systemic manifestations and allow treatment accordingly.


Assuntos
Síndrome de Ehlers-Danlos , Instabilidade Articular , Síndrome de Ehlers-Danlos/classificação , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Instabilidade Articular/etiologia , Instabilidade Articular/fisiopatologia , Instabilidade Articular/terapia , Administração dos Cuidados ao Paciente/métodos
16.
Med Clin North Am ; 103(6): 1055-1075, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582004

RESUMO

This article presents a nongeneticist's guide to understanding the genetics of Parkinson disease (PD), including clinical diagnostic criteria, differential diagnoses, symptom management, when to suspect a hereditary factor, a summary of autosomal dominant and recessive PD genes, and proposed algorithm for genetic testing. There is increasing availability of genetic testing for PD but there are few recommendations on how these tests should be used in clinical practice. This article guides clinicians on the overall management of patients with PD, with emphasis on determining which patients should have genetic testing and how to interpret the results.


Assuntos
Testes Genéticos/métodos , Doença de Parkinson , Algoritmos , Gerenciamento Clínico , Predisposição Genética para Doença , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Doença de Parkinson/terapia
17.
Med Clin North Am ; 103(6): 977-990, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582008

RESUMO

Pharmacogenomics (PGx) is a powerful tool that can predict increased risks of adverse effects and sub-therapeutic response to medications. This article establishes the core principles necessary for a primary care provider to meaningfully and prudently use PGx testing. Key topics include in which patients PGx testing should be considered, how PGx tests are ordered, how the results are translated into clinical recommendations, and what further advancements are likely in the near future. This will provide clinicians with a foundational knowledge of PGx that can allow incorporation of this tool into their practice or support further personal investigation.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacogenética/métodos , Medicina de Precisão , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Atenção Primária à Saúde/métodos
18.
Med Clin North Am ; 103(6): 991-1003, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582009

RESUMO

Genetic causes of liver disease lead to a wide range of presentations. This article describes hereditary hemochromatosis, Gilbert syndrome, alpha-1 antitrypsin deficiency, Wilson disease, PFIC, BRIC, and LAL-D. The most common cause of hereditary hemochromatosis is a C282Y mutation in the HFE gene. Gilbert syndrome is a benign cause of indirect hyperbilirubinemia. Alpha-1 antitrypsin deficiency causes both lung and liver disease. Wilson disease can cause neurologic disease and liver disease. Progressive familial intrahepatic cholestasis and benign recurrent intrahepatic cholestasis are rare causes of cholestasis. LAL-D is a rare disease that can appear similar to NAFLD in adults.


Assuntos
Testes Genéticos , Hepatopatias , Administração dos Cuidados ao Paciente/métodos , Humanos , Hepatopatias/genética , Hepatopatias/terapia
19.
Adv Exp Med Biol ; 1141: 13-100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571164

RESUMO

The transport of specific molecules across lipid membranes is an essential function of all living organisms. The processes are usually mediated by specific transporters. One of the largest transporter families is the ATP-binding cassette (ABC) family. More than 40 ABC transporters have been identified in human, which are divided into 7 subfamilies (ABCA to ABCG) based on their gene structure, amino acid sequence, domain organization, and phylogenetic analysis. Of them, at least 11 ABC transporters including P-glycoprotein (P-GP/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2) are involved in multidrug resistance (MDR) development. These ABC transporters are expressed in various tissues such as the liver, intestine, kidney, and brain, playing important roles in absorption, distribution, and excretion of drugs. Some ABC transporters are also involved in diverse cellular processes such as maintenance of osmotic homeostasis, antigen processing, cell division, immunity, cholesterol, and lipid trafficking. Several human diseases such as cystic fibrosis, sitosterolemia, Tangier disease, intrahepatic cholestasis, and retinal degeneration are associated with mutations in corresponding transporters. This chapter will describe function and expression of several ABC transporters (such as P-GP, BCRP, and MRPs), their substrates and inhibitors, as well as their clinical significance.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Fenômenos Fisiológicos Celulares , Resistência a Múltiplos Medicamentos/genética , Regulação da Expressão Gênica , Humanos , Filogenia
20.
Adv Exp Med Biol ; 1141: 293-340, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571168

RESUMO

Hepatic drug transporters are mainly distributed in parenchymal liver cells (hepatocytes), contributing to drug's liver disposition and elimination. According to their functions, hepatic transporters can be roughly divided into influx and efflux transporters, translocating specific molecules from blood into hepatic cytosol and mediating the excretion of drugs and metabolites from hepatic cytosol to blood or bile, respectively. The function of hepatic transport systems can be affected by interspecies differences and inter-individual variability (polymorphism). In addition, some drugs and disease can redistribute transporters from the cell surface to the intracellular compartments, leading to the changes in the expression and function of transporters. Hepatic drug transporters have been associated with the hepatic toxicity of drugs. Gene polymorphism of transporters and altered transporter expressions and functions due to diseases are found to be susceptible factors for drug-induced liver injury (DILI). In this chapter, the localization of hepatic drug transporters, their regulatory factors, physiological roles, and their roles in drug's liver disposition and DILI are reviewed.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Proteínas de Membrana Transportadoras , Preparações Farmacêuticas , Transporte Biológico , Variação Genética , Hepatócitos , Humanos , Proteínas de Membrana Transportadoras/genética , Preparações Farmacêuticas/metabolismo
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