RESUMEN
ABSTRACT Staphylococcus aureus pandemic clone USA300 has, in addition to its constitutive arginine catabolism (arc) gene cluster, an arginine catabolism mobile element (ACME) carrying another such cluster, which gives this clone advantages in colonisation and infection. Gene arcR, which encodes an oxygen-sensitive transcriptional regulator, is inside ACME and downstream of the constitutive arc gene cluster, and this situation may have an impact on its activation. Different relative expression behaviours are proven here for arcRACME and the arcACME operon compared to the constitutive ones. We also show that the artificially expressed recombinant ArcRACME protein binds to the promoter region of the arcACME operon; this mechanism can be related to a positive feedback model, which may be responsible for increased anaerobic survival of the USA300 clone during infection-related processes.
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Humanos , Operón/genética , Arginina/genética , Staphylococcus aureus/genética , Proteínas Bacterianas/genética , Proteínas de Unión al ADN/genética , Arginina/metabolismo , Staphylococcus aureus/metabolismo , Regulación Bacteriana de la Expresión Génica/genética , Secuencias Repetitivas Esparcidas/genética , Genes Bacterianos/genéticaRESUMEN
ABSTRACT Objective: To evaluate the association between p53 polymorphisms and human papillomavirus (HPV) E6/E7 mRNA expression. Methods: We analyzed 175 cervical samples from women aged 16-69 years old who were tested for HPV E6/E7 mRNA expression (NucliSENS® EasyQ® HPV). The samples were divided into three groups: positive (n = 75) those with positive HPV E6/E7 mRNA expression and positive high-risk HPV Hybrid Capture (HR-HC) test; negative (n = 52) those with negative HPV E6/E7 mRNA expression and positive HR-HC; and control (n = 48) those with negative HPV E6/E7 mRNA expression and negative HR-HC. The p53 polymorphisms at codons 11, 72, and 248 were evaluated through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of the arginine/arginine homozygous genotype at codon 72 was significantly higher in the positive (49.3%) than in the negative (32.7%) and control groups (20.8%, p = 0.002*). The frequency of the arginine allele was also significantly higher in the positive (67.3%) than in the negative (53.8%) and control groups (38.5%, p < 0.001*). The arginine/arginine homozygous genotype was significantly associated with positive HPV E6/E7 mRNA expression (positive group) compared with negative and control groups (odds ratio: 2.633; 95% CI, 1.399-4.954, p = 0.003). The frequency of arginine/arginine homozygous genotype at codon 72 remained significantly more frequent in the positive group of women aged ≥30 years than in the other two groups. Conclusion: The presence of the p53 arginine/arginine homozygous genotype at codon 72 was significantly associated with the positive HPV E6/E7 mRNA expression.
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Humanos , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Papillomaviridae/genética , ARN Mensajero/metabolismo , Proteínas Oncogénicas Virales/genética , Displasia del Cuello del Útero/virología , Infecciones por Papillomavirus/virología , Proteínas E7 de Papillomavirus/genética , Arginina/genética , Polimorfismo de Longitud del Fragmento de Restricción , Codón , ARN Viral , Neoplasias del Cuello Uterino/virología , Reacción en Cadena de la Polimerasa , Proteína p53 Supresora de Tumor/genética , GenotipoRESUMEN
The mandible condylar process cartilage (CP) of Wistar rats is a secondary cartilage and acts as a mandibular growth site. This phenomenon depends on adequate proteins intake and hormone actions, including insulin. Objectives The present study evaluated the morphological aspects and the expression of the insulin receptor (IR) in the cartilage of the condylar process (CP) of rats subjected to protein undernourishment. Material and Methods The nourished group received a 20% casein diet, while the undernourished group (U) received a 5% casein diet. The re-nourished groups, R and RR, were used to assess the effects of re-nutrition during puberty and adulthood, respectively. CPs were processed and stained with picro-sirius red, safranin-O and azocarmine. Scanning electron microscopy and immunohistochemistry were also performed. Results The area of the CP cartilage and the number of cells in the chondroblastic layer decreased in the U group, as did the thickness of the CP layer in the joint and hypertrophic layer. Renourishment during the pubertal stage, but not during the adult phase, restored these parameters. The cell number was restored when re-nutrition occurred in the pubertal stage, but not in the adult phase. The extracellular matrix also decreased in the U group, but was restored by re-nutrition during the pubertal stage and further increased in the adult phase. IR expression was observed in all CPs, being higher in the chondroblastic and hypertrophic cartilage layers. The lowest expression was found in the U and RR groups. Conclusions Protein malnutrition altered the cellularity, the area, and the fibrous cartilage complex, as well as the expression of the IRs. .
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Animales , Ratones , Antiinflamatorios no Esteroideos/metabolismo , Ciclooxigenasa 1/metabolismo , /metabolismo , Inhibidores de la Ciclooxigenasa/metabolismo , Piroxicam/análogos & derivados , Tiazinas/metabolismo , Tiazoles/metabolismo , Sustitución de Aminoácidos , Antiinflamatorios no Esteroideos/química , Arginina/química , Arginina/genética , Arginina/metabolismo , Sitios de Unión , Dominio Catalítico , Ciclooxigenasa 1/química , Ciclooxigenasa 1/genética , /química , /genética , Inhibidores de la Ciclooxigenasa/química , Enlace de Hidrógeno , Leucina/química , Leucina/genética , Leucina/metabolismo , Mutación , Piroxicam/química , Piroxicam/metabolismo , Estructura Secundaria de Proteína , Serina/química , Serina/genética , Serina/metabolismo , Tiazinas/química , Tiazoles/química , Tirosina/química , Tirosina/genética , Tirosina/metabolismo , AguaRESUMEN
Polymorphisms of the p53 gene, which participates in DNA repair, can affect the functioning of the p53 protein. The Arg and Pro variants in p53 codon 72 were shown to have different regulation properties of p53-dependent DNA repair target genes that can affect various levels of cytogenetic aberrations in chronic hepatitis B patients. The present study aimed to examine the frequency of chromosomal aberrations and the mitotic index in patients with chronic hepatitis B and their possible association with p53 gene exon 4 codon 72 Arg72Pro (Ex4+119 G>C; rs1042522) polymorphism. Fifty-eight patients with chronic hepatitis B and 30 healthy individuals were genotyped in terms of the p53 gene codon 72 Arg72Pro polymorphism by PCR-RFLP. A 72-h cell culture was performed on the same individuals and evaluated in terms of chromosomal aberrations and mitotic index. A high frequency of chromosomal aberrations and low mitotic index were detected in the patient group compared to the control group. A higher frequency of chromosomal aberrations was detected in both the patient and the control groups with a homozygous proline genotype (13 patients, 3 control subjects) compared to patients and controls with other genotypes [Arg/Pro (38 patients, 20 control subjects) and Arg/Arg (7 patients, 7 control subjects)]. We observed an increased frequency of cytogenetic aberrations in patients with chronic hepatitis B. In addition, a higher frequency of cytogenetic aberrations was observed in p53 variants having the homozygous proline genotype compared to variants having other genotypes both in patients and healthy individuals.
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Adulto , Femenino , Humanos , Masculino , Codón/genética , Hepatitis B Crónica/genética , Polimorfismo Genético/genética , /genética , Arginina/genética , Estudios de Casos y Controles , Aberraciones Cromosómicas , Predisposición Genética a la Enfermedad , Genotipo , Índice Mitótico , Prolina/genéticaRESUMEN
Background : Oral submucous fibrosis (OSF) may be considered a collagen metabolic disorder resulting from areca-nut alkaloid exposure and individual variation in collagen metabolism. Due to the complexity of OSF pathogenesis, it is important to elucidate independent and interactive effects of polymorphisms of collagen-related genes on OSF risk. Materials and Methods : This study is focused on seven polymorphisms (SNPs) of transforming growth factor-beta-1 (TGF-beta-1) gene in patients with oral submucous fibrosis (OSF), belonging to south Indian ethnic extraction. The mean age at presentation was 43.9 years, range 23-72 years (n=50, M:F ratio, 2.6:1). DNA samples from 50 subjects of the same ethnic group and comparable demographic features who have had practiced the habit of areca-chewing of almost equal duration, but remained free of disease constituted the controls. All DNA samples were collected progressively and purified from peripheral blood employing standard protocols and tested for SNPs. They included two polymorphisms in the promoter region (C-509T and G-800A), three polymorphisms in exon-1 (Arg25Pro(G915C), Leu10Pro(T869C), Glu47Gly(A979G) and two in 5 ͲUTR regions (C→T(rs13306708) and G→A (rs9282871). The extracted DNA samples along with the primers underwent PCR amplification and the genotypic and allelic frequencies were calculated. All calculations were performed using the SPSS software. The PCR products were purified and subsequently sequenced using Flour S™ multi-imager system (Biorad). The sequenced data were analyzed using the BioEdit sequence analysis software. Results : Out of the seven polymorphisms analyzed, six such as two in the promoter region, three in exon-1 and one in 5¢UTR were found to have a " P" value above 0.05 and hence were not significant. The C→T transition (rs13306708) in the 5¢UTR region recorded a " P" value of 0.03 on comparison and hence was found to be significant. The allelic frequencies for this C→T transition in patients were 68.7% C and 31.2% T (27CC, 15CT, 8TT) and that in controls were 89.5% C and 10.4% T (42CC, 6CT, 2TT). Conclusions : The polymorphism in 5¢UTR C-T in TGF beta 1 gene has a significant association with OSF, being a prime determinant in the pro-angiogenic pathway which has got direct bearing with the pathophysiology of the disease. The proximity of this polymorphism to the transcription site and the associated risk involved is discussed.
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Regiones no Traducidas 5'/genética , Adenina , Adulto , Anciano , Areca , Arginina/genética , Mapeo Cromosómico , Citosina , Etnicidad/genética , Exones/genética , Femenino , Frecuencia de los Genes/genética , Genotipo , Glutamina/genética , Glicina/genética , Guanina , Humanos , India , Leucina/genética , Masculino , Persona de Mediana Edad , Fibrosis de la Submucosa Bucal/genética , Fibrosis de la Submucosa Bucal/inmunología , Polimorfismo de Nucleótido Simple/genética , Prolina/genética , Regiones Promotoras Genéticas/genética , Timina , Factores de Tiempo , Factor de Crecimiento Transformador beta1/genética , Adulto JovenRESUMEN
Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of diabetes within the first six months of life and insulin dependence life long. It has been recently discovered that mutation in KCNJ11 gene encoding Kir6.2, the pore forming subunit of ATP sensitive potassium channel (K ATP) is the most common cause and such patients may respond better to oral sulphonylurea drugs than insulin. Here is a rare case of permanent neonatal diabetes due to R20IC mutation in KCNJ11 gene.
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Sustitución de Aminoácidos/genética , Arginina/genética , Glucemia/metabolismo , Cisteína/genética , Análisis Mutacional de ADN , Diabetes Mellitus Tipo 1/diagnóstico , Cetoacidosis Diabética/sangre , Femenino , Gliburida/administración & dosificación , Tamización de Portadores Genéticos , Humanos , Hipoglucemiantes/administración & dosificación , Lactante , Recién Nacido , Insulina/administración & dosificación , Lesión Renal Aguda/sangre , Canales de Potasio de Rectificación Interna/genéticaRESUMEN
Over 50% of all human cancers involve p53 mutations,which occur mostly in the sequence-specific DNA-binding central domain (p53c), yielding little/non-detectable af?nity to the DNA consensus site.Despite our current understanding of protein-DNA recognition,the mechanism(s) underlying the loss in protein-DNA binding afnity/ specificity upon single-point mutation are not well understood. Our goal is to identify the common factors governing the DNA-binding loss of p53c upon substitution of Arg 273 to His or Cys,which are abundant in human tumours. By computing the free energies of wild-type and mutant p53c binding to DNA and decomposing them into contributions from individual residues, the DNA-binding loss upon charge/noncharge -conserving mutation of Arg 273 was attributed not only to the loss of DNA phosphate contacts, but also to longer-range structural changes caused by the loss of the Asp 281 salt-bridge. The results herein and in previous works suggest that Asp 281 plays a critical role in the sequence-specific DNA-binding function of p53c by (i)orienting Arg 273 and Arg 280 in an optimal position to interact with the phosphate and base groups of the consensus DNA, respectively, and (ii) helping to maintain the proper DNA-binding protein conformation.
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Sustitución de Aminoácidos/genética , Arginina/genética , Sitios de Unión/genética , Cisteína/genética , ADN/genética , Humanos , Mutación Puntual , Unión Proteica/genética , Termodinámica , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Com o uso da ultra-sonografia de alta resolução, a prevalência de nódulos tem aumentado e, conseqüentemente, o número de punção aspirativa por agulha fina (PAAF), que é o método de escolha para diagnóstico inicial. Um dos maiores dilemas clínicos para o citologista é o diagnóstico diferencial das lesões foliculares comumente agrupadas na classe padrão folicular. Neste artigo de revisão, discutiremos quais são as lesões que podem ser assim classificadas e os marcadores moleculares, identificados por nós ou por outros grupos, que são capazes de distinguir as lesões benignas das malignas.
There are an increasing number of thyroid nodules found by ultrasound and sampled by fine needle aspiration (FNA). A clinical problem is the accurate distinction between benign and malignant forms of follicular lesion. In this review we discuss the thyroid lesions that are common sources of diagnostic error, and grouped together as follicular patterned lesion, and the molecular markers identified by us and others, and that are able to distinguish the benign from the malignant ones.
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Humanos , Adenocarcinoma Folicular/diagnóstico , Adenoma/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/diagnóstico , Biomarcadores de Tumor/análisis , Adenocarcinoma Folicular/genética , Adenoma Oxifílico/diagnóstico , Adenoma Oxifílico/genética , Adenoma/genética , Arginina/genética , Biopsia con Aguja Fina , Diagnóstico Diferencial , Perfilación de la Expresión Génica , Inmunohistoquímica , Proteínas de la Membrana/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Factores de Transcripción Paired Box , PPAR gamma/genética , Sensibilidad y Especificidad , Factor de Transcripción CHOP , Neoplasias de la Tiroides/genética , Nódulo Tiroideo/genética , Biomarcadores de Tumor/genéticaRESUMEN
RACIONAL: Polimorfismos genéticos são variações genéticas que podem ocorrer em seqüências codificadoras e não-codificadoras, levando a alterações qualitativas e/ou quantitativas das proteínas em questão. O p53 é o gene mais comumente alterado no câncer humano. O polimorfismo desse gene no códon 72 ocorre por substituição de uma base e tem sido associado a maior risco de câncer. OBJETIVO: Determinar a possível associação entre o polimorfismo no códon 72 (72 arginina/prolina) do gene p53 e câncer colorretal. CASUíSTICA E MÉTODOS: Foram avaliados em 100 pacientes com câncer colorretal e em 100 indivíduos sem câncer, pareados quanto ao sexo idade, o hábito de fumar, o etilismo e no grupo caso o estádio, o grau de diferenciação e a evolução da doença. O genótipo (72 arginina/prolina) foi determinado por PCR, utilizando-se primers (seqüências de nucleotídeos) específicos. RESULTADOS: O genótipo homozigoto arginina/arginina foi prevalente em 56 por cento no grupo controle e em 58 por cento no grupo caso. Não se observou diferença entre os dois grupos. No estádio IV este genótipo foi mais freqüente quando comparado ao estádio I (80 por cento versus 14 por cento). Não se observou diferença entre as variações do genótipo e fumo, álcool, evolução clínica ou grau de diferenciação. CONCLUSAO: A prevalência do genótipo arginina/arginina foi a mais freqüente nos dois grupos. Não foi encontrada correlação entre maior risco de câncer e o polimorfismo no códon 72 prolina/arginina do gene p53. Apesar do pequeno número de doentes com câncer em estádio avançado (IV), estes tiveram maior prevalência do genótipo arginina/arginina.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Arginina/genética , Neoplasias Colorrectales/genética , /genética , Polimorfismo Genético , Prolina/genética , Alelos , Estudios de Casos y Controles , Codón , Genotipo , Predisposición Genética a la Enfermedad/genética , Estilo de Vida , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Prevalencia , Biomarcadores de Tumor/genéticaRESUMEN
Venous thrombosis is a multicausal disease, more than one genetic risk factor may cooperate to effect thrombotic risk. Factor V Leiden is found to be an important hereditary risk factor for venous thromboembolism. Analogous to factor V Leiden, a point mutation at amino acid positions Arg336 and Arg562 in factor VIII may predispose patients to thrombosis. Eighty-one Thai patients with venous thrombosis and 100 Thai healthy volunteers have been studied. Neither heterozygous nor homozygous mutations were detected both thrombosis patients or normal volunteers. However, further studies with larger samples of venous thrombosis patients are recommended.
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Adulto , Anciano , Sustitución de Aminoácidos , Arginina/genética , Secuencia de Bases , Estudios de Casos y Controles , Cartilla de ADN , Factor VIII/genética , Femenino , Heterocigoto , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa , Proteína C/química , Tailandia , Trombosis de la Vena/genéticaRESUMEN
A common polymorphism of the wild type p53 is known at codon 72 of exon 4, with 2 alleles encoding either arginine (CGC, p53Arg) or proline (CCC, p53Pro). A recent study suggested that this polymorphism affects the susceptibility of p53 protein to human papillomavirus E6 oncoprotein mediated degradation and that individuals homozygous for p53Arg are seven times more susceptible to HPV-associated carcinogenesis of the cervix than heterozygotes. To examine whether the p53Arg genotype could be a risk factor for HPV-associated cervical carcinomas in the Korean population, we analyzed the p53 codon 72 polymorphism status of HPV-positive invasive cervical carcinomas from 52 Korean women and 103 healthy control samples. The proportion of individuals homozygous for p53Arg, homozygous for p53Pro, and heterozygous for the two alleles were 40%, 19%, and 41% in normal healthy controls; 42%, 17%, and 40% in women with HPV-positive invasive cervical carcinoma. There were no significant differences in the distribution of p53 genotypes between controls and cervical carcinomas. This finding indicates that the p53Arg genotype is not associated with an increased susceptibility to cervical carcinoma in Korean women.
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Femenino , Humanos , Alelos , Arginina/genética , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/genética , Codón/genética , Genes p53/genética , Predisposición Genética a la Enfermedad , Genotipo , Papillomaviridae/genética , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Prolina/genética , Proteína p53 Supresora de Tumor/genética , Factores de RiesgoRESUMEN
We report a Korean family case of beta-thalassemia minor and Hb Queens. This is the first case report of Hb Queens in Korea. A 43-year-old male and his four family members had beta-thalassemia minor which is very rare in Korea. Incidentally, an alpha chain variant with a high isoelectric point was also found in two other family members without clinical problems and was finally identified as alpha 34 (B15) Leu-Arg or Hemoglobin Queens.