RESUMO
Hypersensitivity reaction to abacavir (ABC hypersensitivity syndrome, AHS) is strongly associated with the presence of the HLA-B*57:01 allele. This study was designed to estimate the prevalence of HLA-B*57:01 allele in Argentinean HIV-1 infected patients. We analyzed the presence of HLA-B*57:01 allele in 1646 HIV-1 infected patients from different regions of Argentina. This allele was detected in 81 patients; most of them corresponded to patients living in the central region of the country. The prevalence of HLA-B*57:01 was 4.9%, similar to other Caucasian populations and higher than other data reported for South American populations. This strongly supports screening for the presence of HLA-B*57:01 in abacavir treatment of HIV-1 in our country.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/genética , Infecções por HIV/genética , Antígenos HLA-B/genética , Adulto , Alelos , Fármacos Anti-HIV/administração & dosagem , Argentina , Didesoxinucleosídeos/administração & dosagem , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/imunologia , Feminino , Expressão Gênica , Frequência do Gene , Testes Genéticos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Antígenos HLA-B/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Gel-based electrodes are employed to record sEMG signals for prolonged periods. These signals are used for the control of myoelectric prostheses, clinical analysis, or sports medicine. However, when the gel dries, the electrode-skin impedance increases considerably. Using dry active electrodes (AEs) to compensate variations of impedance is an alternative for long-term recording. This work describes the optimization of the electronic design of a conventional AE by removing the impedance coupling stage and two filters. The proposed work consisted of 5 stages: electrodes, amplification (X250), 2.2 Vdc offset, low-pass filter, and ADC with USART communication. The device did not need the use of electrolytic gel. The measurements of CMRR (96 dB), amplitude of the output sEMG signal (â¼1.6 Vp-p), and system bandwidth (15-450 Hz) were performed in order to confirm the reliability of the device as an sEMG signal acquisition system. The SNR values from seven movements performed by eleven volunteers were compared in order to measure the repeatability of the measurements (average 30.32 dB for a wrist flexion). The SNR for wrist flexion measured with the proposed and the commercial system was compared; the values were 49 dB and 60 dB, respectively.
Assuntos
Cobre , Eletrodos , Eletroencefalografia/métodos , Eletromiografia/métodos , Dispositivos Eletrônicos Vestíveis , Articulação do Punho/fisiologia , Zinco , Adulto , Comunicação , Impedância Elétrica , Eletrônica , Feminino , Géis , Humanos , Masculino , Movimento , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , PunhoRESUMO
This study aim to determine the proportion of traffic rule infractions in Cali, Colombia, in places where a road traffic injury (RTI) occurred. Description of videotaping of sites where a person was injured in an RTI in 2009. Counts of road users and infractions were established for each road user group and were compared using a Z-test. They were found 13,491 users, distributed as follow: 8.9% were pedestrians, 4.6% cyclists, 24.6% motorcyclists, and 61.8% were automobile drivers. The most frequent traffic violation among motorcyclists was transiting on lines designated for other vehicles (55.2%). Among cyclists, the most frequent violations were transiting without a helmet (99.2%) and not wearing the designated vest (100%). Among pedestrians, crossing streets at prohibited places (77.3%), even at sites where a pedestrian bridge was present (72.7%), represented two common violations. Vulnerable road users committed more traffic infractions than automobile drivers (p < 0.001). High rates of traffic rule infractions among vulnerable road users were observed. Studies to better understand the occurrence of these behaviours and the promotion of effective interventions are warranted.
Assuntos
Acidentes de Trânsito , Condução de Veículo , Regulamentação Governamental , Colômbia/epidemiologia , Humanos , Motocicletas , Prevalência , Segurança , Gravação de Videoteipe , Ferimentos e LesõesRESUMO
We describe an EBV-driven lytic system (LySED) that can be used to specifically target therapy to EBV- containing tumors. This system takes advantage of the transactivating properties of EBNA-1, a latency protein expressed in all EBV-containing cells, to drive the expression of Zta, a gene sufficient for inducing the EBV lytic cycle. Thus, EBV provides both the target and the executor for mediating tumor-specific cell death, markedly increasing the specificity of the system. Transfection of EBV-positive cell lines with the LySED construct resulted in a switch to lytic cycle and subsequent cell death, even in the presence of an inhibitor of EBV thymidine kinase (acyclovir) without an increase in virion production. In contrast, growth of EBV-negative B-cell lines was not affected.
Assuntos
Antígenos Virais/genética , Proteínas de Ligação a DNA/genética , Herpesvirus Humano 4/genética , Neoplasias/terapia , Sequência de Bases , Morte Celular , Antígenos Nucleares do Vírus Epstein-Barr , Humanos , Dados de Sequência Molecular , Neoplasias/genética , Neoplasias/patologia , Neoplasias/virologia , Ativação Transcricional , Transfecção , Latência ViralRESUMO
An invariant genetic lesion in mouse plasmacytomas is deregulated expression of c-myc as a consequence of chromosomal translocation. However, retroviral and transgenic studies suggest that additional genetic lesions may contribute to the genesis of plasmacytomas. The p53 tumor suppressor gene is a likely contributor to this genetic lesion, since there is a high incidence of p53 mutation in Burkitt's lymphomas and B-ALL (L3), both of which contain translocations involving c-myc analogous to those in plasmacytomas. In addition, p53 has been shown to be a transcriptional modulator of c-myc expression. In a survey of 27 mouse plasmacytomas by single-strand conformation polymorphism, we identified a single mutation (3.7% incidence), suggesting that p53 lesions are not frequent contributors to plasmacytomagenesis. A similar study of macrophage-monocyte tumors generated by a c-myc-containing retrovirus also indicates a lack of p53 involvement in deregulated c-myc expression. These results suggest that the specific maturation stage of transformed B-lymphocytes, independent of c-myc deregulation, may be the critical factor which determines the involvement of mutant p53.
Assuntos
Regulação Neoplásica da Expressão Gênica , Genes myc , Genes p53 , Mutação , Plasmocitoma/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Éxons , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos , Oligonucleotídeos Antissenso , Reação em Cadeia da Polimerase , Polimorfismo GenéticoRESUMO
Available evidence suggests that, among hematological malignancies, p53 is most often mutated in Burkitt's lymphoma (BL). However, much of the published data is based on cell lines. We have, therefore, analyzed BL biopsies to determine more accurately the frequency and pattern of p53 mutations in primary tumors and to determine whether there are differences among the various subtypes of BL. Among 27 BL biopsies from South Africa, we have observed mutations in the p53 gene (exons 5 through 8) in 37% of tumors. The higher frequency of mutations in cell lines (70%) suggests that mutation of p53 may be associated with tumor progression. Summarizing available data we conclude that the presence of mutated p53 in BL is independent of the geographic origin of the tumor, the 8;14 chromosomal breakpoint locations and Epstein-Barr virus association. We also find that the mutational spectrum of p53 in BL differs from that observed in nonlymphoid tumors. More than 50% of mutations in BL are clustered in a small stretch of 33 amino acids (codons 213 to 248). Interestingly, codon 213 appears to be as frequently mutated as codon 248. Conversely, codon 273, often mutated in solid tumors, is rarely involved in BL.
Assuntos
Linfoma de Burkitt/genética , Genes p53 , Mutação , Neoplasias/genética , Sequência de Aminoácidos , Sequência de Bases , Códon/genética , Éxons , Humanos , Íntrons , Polimorfismo Genético , América do Sul , Proteína Supressora de Tumor p53/genéticaRESUMO
We have analyzed the Fas-mediated death pathway in a panel of 11 Epstein-Barr virus (EBV)-negative and 10 EBV-positive Burkitt's lymphoma (BL) cell lines. We show that the increased expression of Fas in EBV-positive cell lines is mediated via LMP-1. Four of the 21 BL cell lines are readily responsive to Fas-mediated cell death signals. Of the remaining 17 cell lines, 10 can be sensitized by up-regulating Fas either via exogenous expression of LMP-1 or via treatment with CD40L. These same cell lines can also be sensitized by treatment with cycloheximide (CHX), which, however, does not result in up-regulation of Fas. Neither up-regulation of Fas, nor treatment with CHX, restore Fas sensitivity in seven BL cell lines. Further analyses indicated that 5 of the 7 cell lines (and none of the 14 responsive cell lines) were also compromised in the integrity/expression of the proapoptotic gene Bax. Thus, in most BL cell lines, the Fas pathway seems to be inhibited, although the mechanism of inhibition varies. The correlation between Bax mutation and irreversible (by CD40L or CHX) Fas resistance raises the possibility, for the first time, that Bax may play a critical function in Fas-mediated cell death in BL.
Assuntos
Apoptose/fisiologia , Linfoma de Burkitt/patologia , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas/fisiologia , Receptor fas/fisiologia , Animais , Apoptose/efeitos dos fármacos , Linfócitos B/metabolismo , Linfócitos B/patologia , Linfoma de Burkitt/imunologia , Linfoma de Burkitt/virologia , Ligante de CD40 , Cicloeximida/farmacologia , Herpesvirus Humano 4/metabolismo , Humanos , Glicoproteínas de Membrana/farmacologia , Camundongos , Inibidores da Síntese de Proteínas/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , Sensibilidade e Especificidade , Células Tumorais Cultivadas , Infecções Tumorais por Vírus/metabolismo , Infecções Tumorais por Vírus/patologia , Proteínas da Matriz Viral/biossíntese , Proteína X Associada a bcl-2 , Receptor fas/biossínteseRESUMO
Burkitt's lymphoma (BL) cell lines carry a translocated c-myc gene and, in 60-80% of cases, exhibit mutations in the p53 tumor suppressor gene. We examined the potential role of the p53 gene in BL tumorigenicity using an in vitro assay that measures p53-dependent cell cycle arrest in the G1 phase of the cell cycle and an in vivo athymic murine model that detects differences in the tumorigenicity of BL cell lines. A highly significant inverse correlation was found between the ability of BL cells to arrest in G1 after irradiation and their tumorigenicity in athymic mice, consistent with the notion that loss of p53 function is associated with increased tumorigenicity. Inactivation of wild-type (wt) p53 function by expression of the human papillomavirus E6 protein in the AG876V BL cell line, which carries both wt and mutant p53 proteins, rendered the cell line significantly more tumorigenic in athymic mice. Transfection of the wt p53 gene into the p53 mutant and highly tumorigenic BL-41 cell line caused it to acquire wt p53 function and rendered it less tumorigenic in mice. In addition to confirming a role for the loss of p53 function in tumor progression, the data demonstrate that wt p53 protein can reduce BL tumorigenicity in vivo.
Assuntos
Linfoma de Burkitt/genética , Ciclo Celular/fisiologia , Genes p53/genética , Animais , Biópsia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mutação , Transplante de Neoplasias , Nocodazol/farmacologia , Polimorfismo Conformacional de Fita Simples , Transfecção , Células Tumorais Cultivadas/efeitos da radiaçãoRESUMO
Objectives. To present a quantitative comparison of thermal patterns produced by the piston-in-a-baffle approach with those generated by a physiotherapy ultrasonic device and to show the dependency among thermal patterns and acoustic intensity distributions. Methods. The finite element (FE) method was used to model an ideal acoustic field and the produced thermal pattern to be compared with the experimental acoustic and temperature distributions produced by a real ultrasonic applicator. A thermal model using the measured acoustic profile as input is also presented for comparison. Temperature measurements were carried out with thermocouples inserted in muscle phantom. The insertion place of thermocouples was monitored with ultrasound imaging. Results. Modeled and measured thermal profiles were compared within the first 10 cm of depth. The ideal acoustic field did not adequately represent the measured field having different temperature profiles (errors 10% to 20%). Experimental field was concentrated near the transducer producing a region with higher temperatures, while the modeled ideal temperature was linearly distributed along the depth. The error was reduced to 7% when introducing the measured acoustic field as the input variable in the FE temperature modeling. Conclusions. Temperature distributions are strongly related to the acoustic field distributions.
Assuntos
Modelos Biológicos , Modalidades de Fisioterapia , Terapia por Ultrassom/métodos , Animais , HumanosRESUMO
It has previously been demonstrated that chicken red cells have a receptor with the capacity to bind aggregated IgG, IgM 7 S or antigen-complex IgG. This receptor was isolated from Nonidet P-40 soluble extracts of chicken red cells by immunoadsorption with either immobilized aggregated IgG or monomeric IgM (IgM 7 S) and further gel filtration through a Sephacryl S-300 column. The Fc binding material was characterized as a glycoprotein with a molecular weight of 30,000 which retained its Fc receptor activity after the isolation procedure. This was demonstrated by its capacity to inhibit the binding of 125I-IgM 7 S or 125I-labelled aggregated IgG to chicken red cells. After Bacillus cereus phospholipase C treatment the Fc receptor activity remained unchanged, but the molecular weight (15,000) did not, suggesting that the phospholipids cleaved by this treatment were not essential for the interactions of the receptor with specific ligands. However, this Fc-binding component was shown to have a molecular weight of 13,000 and a diminished Fc receptor activity after reduction with dithiothreitol, suggesting the presence of at least one disulphide bridge, necessary to maintain the total ligand-binding activity.
Assuntos
Eritrócitos/metabolismo , Receptores Fc/isolamento & purificação , Animais , Fenômenos Químicos , Físico-Química , Galinhas , Cromatografia em GelRESUMO
Multiple genes have been shown to be independently hypermethylated in lymphoid malignancies. We report here on the extent of concurrent methylation of E-cadherin, Dap-kinase, O(6)MGMT, p73, p16, p15 and p14 in 129 pediatric ALL cases. While most of these genes demonstrated methylation in a proportion of cases, O(6)MGMT, p16 and p14 were infrequently methylated (11, 7 and 3%, respectively). Methylation of at least one gene was found in the vast majority (83%) of cases. To determine the extent and concordance of methylation we calculated a methylation index (MI=number of methylated genes/number of studied genes) for each sample. The average MI was 0.28, corresponding to 2/7 methylated genes. MI was correlated with standard prognostic factors, including immunophenotype, age, sex, WBC and presence of specific translocations (TEL-AML1, BCR-ABL, E2A-PBX1 or MLL-AF4). We determined that children >/=10 years old and children presenting with high WBC (>/=50 x 10(9)/l) both associated with a higher MI (P<0.01 and <0.05, respectively). T-ALLs demonstrated a lower MI (median=0.17) than precursor B ALLs (median=0.28). Among the different molecular subgroups, MLL-ALLs had the highest MI (mean=0.35), while ALLs carrying the t(1;19) had the lowest MI (mean=0.07). The most common epigenetic lesion in childhood ALL was methylation of E-cadherin (72%) independent of the molecular subtype or other clinicopathological factors.
Assuntos
Proteínas de Ciclo Celular , Metilação de DNA , DNA de Neoplasias/genética , Proteínas Nucleares/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Supressoras de Tumor , Adolescente , Proteínas Reguladoras de Apoptose , Caderinas/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Criança , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core , Ilhas de CpG , Inibidor de Quinase Dependente de Ciclina p15 , Inibidor p16 de Quinase Dependente de Ciclina/genética , Primers do DNA/química , Reparo do DNA , Proteínas de Ligação a DNA/genética , Proteínas Quinases Associadas com Morte Celular , Feminino , Genes Supressores de Tumor , Genes p53/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , O(6)-Metilguanina-DNA Metiltransferase/genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Fenótipo , Reação em Cadeia da Polimerase , RNA Neoplásico/genética , Fatores de Transcrição/genética , Translocação Genética , Proteína Tumoral p73 , Proteína Supressora de Tumor p14ARF/genéticaRESUMO
PCR was used to screen EBV-positive lymphomas from endemic and sporadic Burkitt's lymphoma patients, including EBV-positive lymphomas derived from patients with HIV infection. Only 10% of sporadic lymphomas from either North America (1/15) or South America (2/14) were associated with the type 2 EBV strain, whereas 50% (8/16) of lymphomas from equatorial Africa and 46% (10/22) of HIV-associated lymphomas were positive for the type 2 strain. These data, in conjunction with previous reports, suggest that the proportions of strain types in Burkitt's lymphoma reflect the proportions of strain types in peripheral lymphocytes, and not simply the prevailing regional strain. The increased association of the type 2 strain in lymphocytes and lymphomas from HIV-infected individuals and from Africa may be a result of intermittent (malaria) or continuous (HIU) compromise of immune function in these populations.
Assuntos
Linfoma de Burkitt/microbiologia , Herpesvirus Humano 4/genética , Linfoma Relacionado a AIDS/microbiologia , Infecções Tumorais por Vírus/microbiologia , África/epidemiologia , Sequência de Bases , Linfoma de Burkitt/epidemiologia , Genótipo , Herpesvirus Humano 4/classificação , Humanos , Dados de Sequência Molecular , América do Norte/epidemiologia , Reação em Cadeia da Polimerase , América do Sul/epidemiologiaRESUMO
PURPOSE: To evaluate the effects of thermal dependence of speed of sound (SOS) and acoustic absorption of biological tissues during noninvasive focused ultrasound (US) hyperthermia therapy. METHODS: A finite element (FE) model was used to simulate hyperthermia therapy in the liver by noninvasive focused US. The model consisted of an ultrasonic focused transducer radiating a four-layer biological medium composed of skin, fat, muscle, and liver. The acoustic field and temperature distribution along the layers were obtained after 15 s of hyperthermia therapy using the bio-heat equation. The model solution was found with and without the thermal dependence of SOS and acoustic absorption of biological tissues. RESULTS: The inclusion of the thermal dependence of the SOS generated an increment of 0.4 mm in the longitudinal focus axis of the acoustic field. Moreover, results indicate an increment of the hyperthermia area (zone with temperature above 43 °C), and a maximum temperature difference of almost 3.5 °C when the thermal dependence of absorption was taken into account. CONCLUSION: The increment of the achieved temperatures at the treatment zone indicated that the effects produced by the thermal dependence of SOS and absorption must be accounted for when planning hyperthermia treatment in order to avoid overheating undesired regions.
Assuntos
Hipertermia Induzida , Modelos Biológicos , Terapia por Ultrassom , Acústica , Som , TemperaturaRESUMO
Epstein-Barr virus (EBV) is linked to a spectrum of human diseases including epithelial and lymphoid malignancies in which it exists predominantly in a latent state. EBV is capable of establishing replicative infection at oropharyngeal and genital sites. Replicative EBV infection also occurs in oral hairy leukoplakia, in EBV associated lymphoproliferative disorders, and to a minor degree in nasopharyngeal carcinomas. Recent evidence also suggests that EBV replication, also, may be associated with AIDS related lymphomas and Hodgkin's disease. However it is widely believed that virus in circulating B-lymphocytes and in B-cell malignancies is stringently latent. We now show that by Southern blot analysis we can detect replicative forms of virion DNA in 14.5% (8 of 55) of EBV-positive Burkitt's lymphoma biopsies. This may be the explanation for the elevation of the titres of lytic cycle EBV antigens that is associated with presentation and relapse of EBV associated Burkitt's lymphoma.
Assuntos
Linfoma de Burkitt/microbiologia , Replicação do DNA/fisiologia , DNA Viral/fisiologia , Herpesvirus Humano 4/fisiologia , Replicação Viral/fisiologia , Biópsia , Linfoma de Burkitt/patologia , DNA Viral/genética , Genoma Viral , Herpesvirus Humano 4/genética , Humanos , Linfoma Relacionado a AIDS/microbiologia , Plasmídeos/genéticaRESUMO
The clinical presentation of Burkitt's lymphoma (BL) and it's association with the Epstein-Barr virus (EBV) varies in different geographic areas, BL in developing countries being "intermediate" between the sporadic and endemic types, both in it's clinical presentation and it's association with EBV, which varies from 25-80%. In this study we have analysed the clinical features, EBV association, subtype and prevalence of the deleted variant of the Latent Membrane Protein-1 (LMP-1) of EBV in forty-two cases from two developing countries- India (n = 25) and Argentina (n = 17). In both countries the abdomen was the site most commonly involved while jaw involvement was rare. EBV was detected by in-situ hybridization using the EBER-1 RNA probe. 47% of cases from Argentina and 80% of cases from India were EBER positive. EBV typing using EBNA-3C primers showed a predominance of Type A in both countries (India-13/16 and Argentina-(7/8)). The 30bp deletion of the LMP-1 gene was detected in all evaluated cases from Argentina while the wild type of the gene was seen in all the evaluable Indian cases. Our study highlights the similarities and differences in the clinical presentation and EBV association of BL in two developing countries and also indicates that the subtype of EBV and prevalence of the LMP-1 deletion may reflect the predominant subtype in a particular population.
Assuntos
Linfoma de Burkitt/virologia , Herpesvirus Humano 4 , Adolescente , Adulto , Argentina/epidemiologia , Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , DNA Viral/sangue , Países em Desenvolvimento , Feminino , Secções Congeladas , Herpesvirus Humano 4/classificação , Herpesvirus Humano 4/genética , Humanos , Imunofenotipagem , Índia/epidemiologia , Lactente , Masculino , Proteínas da Matriz Viral/genéticaRESUMO
Epstein-Barr virus (EBV) associated with lymphoid neoplasms demonstrates preferential association with certain viral strains. Previous subtyping studies have however been confined to analysis of sequence variability within a single locus in EBV. Variations have now been reported for several latently expressed EBV genes, including, EBNAs-1, 2 and LMP-1. Variant EBNA-1 strains have been identified in Burkitt's lymphomas and clustering of subtypes for LMP and EBNA-2 have been associated with either malignancy and/or clinical disease. To investigate the linkage between the variability in these three loci in EBV associated with lymphoid malignancies, we subclassified EBV-associated lymphoproliferations (9 reactive and 24 malignant) from HIV-negative and HIV-positive patients by analysis of the EBNA-1, LMP1, and EBNA-2 genes. Our results demonstrate that (1) EBV identical to the prototype B95.8 strain (Type 1 EBNA-2, wild type EBNA-1 and LMP-1) is very rarely associated with tumors. (2) The EBNA-1 variant V-leucine, restricted to malignant lymphomas in immunocompetent patients, was readily identified in non-malignant lesions in HIV infected patients. (3) Variations of EBNA-1 occur independent of variations at other loci.
Assuntos
Soronegatividade para HIV , Soropositividade para HIV/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Linfoma/virologia , Antígenos Virais/genética , Linfoma de Burkitt/genética , Linfoma de Burkitt/virologia , Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/genética , Marcadores Genéticos , Genótipo , Soronegatividade para HIV/genética , Soropositividade para HIV/genética , Humanos , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/virologiaRESUMO
Starting from a pool of 10(13) RNA sequences, we isolated a number of TAR RNA variants after nine rounds of selection by binding to recombinant Tat in vitro (SELEX procedure). Sequence analysis of part of the selected molecular species indicated that two TAR variants (clones A and B) were, respectively, represented five and four times. These two groups of sequences constituted approximately 25% of the total number of analyzed clones (9/34). As far as the primary and presumptive secondary structures of the wild-type TAR are concerned, the selected A and B variants showed an almost complete sequence conservation of the Tat-binding domain, but the configuration of this nucleotide region differed within the secondary structure. Despite this difference, as verified by gel retardation and filter binding assays, both the A and B variants bound Tat in vitro with an affinity that was very close to that of the wild-type TAR. Conversely, neither variant sustained Tat-mediated trans-activation in vivo when they replaced the wild-type TAR inside the long terminal repeat of HIV_1. Taken together, our results suggest that these TAR variants have lost the ability to bind cell factor(s) in vivo and may therefore represent useful decoys for the inhibition of HIV-1 replication.
Assuntos
Produtos do Gene tat/genética , Variação Genética , HIV-1/genética , RNA Viral/genética , Sequência de Bases , Sítios de Ligação/genética , Biotecnologia , Clonagem Molecular , Primers do DNA/genética , Produtos do Gene tat/metabolismo , Repetição Terminal Longa de HIV , HIV-1/metabolismo , Humanos , Técnicas In Vitro , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Reação em Cadeia da Polimerase , RNA Viral/química , RNA Viral/metabolismo , Ativação Transcricional , Transfecção , Produtos do Gene tat do Vírus da Imunodeficiência HumanaRESUMO
Loss of heterozygosity of chromosome 12p in human precursor B-cell ALL invariably results in loss of TEL coding sequences. Accompanied by a 12;21 translocation, such loss of heterozygosity ensures complete loss of the wild-type TEL. No inactivating mutations of the retained TEL allele have been reported in leukemias with hemizygous deletion. However, only minimal data reported the expression of the wild-type TEL in ALL. We now demonstrate that quantitative real-time RT-PCR from leukemic RNA samples could be indicative of compromised TEL expression in childhood ALL and therefore loss of TEL function.
Assuntos
Biomarcadores Tumorais , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Adolescente , Alelos , Southern Blotting , Criança , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core , Metilação de DNA , DNA Complementar/metabolismo , Proteínas de Ligação a DNA , Feminino , Deleção de Genes , Humanos , Lactente , Perda de Heterozigosidade , Masculino , Mutação , Proteínas Nucleares , Proteínas de Fusão Oncogênica/biossíntese , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-ets , RNA/metabolismo , Proteínas Repressoras , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Temperatura , Translocação Genética , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
PURPOSE: During arthroscopy of the shoulder, the ability to pass the arthroscope easily between the humeral head and the glenoid at the level of the anterior band of the inferior glenohumeral ligament is considered a positive drive-through sign. The drive-through sign has been considered diagnostic of shoulder instability and has been associated with shoulder laxity and with SLAP lesions. The goal of this study was to examine the prevalence of the drive-through sign in patients undergoing shoulder arthroscopy and to determine its relationship to shoulder instability, shoulder laxity, and to SLAP lesions. TYPE OF STUDY: Case series. METHODS: We prospectively studied 339 patients undergoing arthroscopy of the shoulder for a variety of diagnosis from 1992 to 1998. The drive-through sign was performed with the patients in a lateral decubitus position and under general anesthesia. The drive-through sign was correlated with preoperative physical findings, intraoperative laxity testing, and with intra-articular pathology at the time of arthroscopy. RESULTS: The arthroscopic evaluation showed that drive-through sign was positive in 234 (69%) shoulders. For the diagnosis of instability, the drive-through sign had a sensitivity of 92%, a specificity of 37. 6%, a positive predictive value of 29.9%, a negative predictive value of 94.2%, and an overall accuracy of 49%. There was an association between the drive-through sign and increasing shoulder laxity, but not with SLAP lesions. CONCLUSIONS: This study shows that a positive drive-through sign is not specific for shoulder instability but is associated with shoulder laxity. This arthroscopic sign should be incorporated with other factors when considering the diagnosis of instability.
Assuntos
Artroscopia/métodos , Instabilidade Articular/diagnóstico , Lesões do Ombro , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Período Intraoperatório , Instabilidade Articular/cirurgia , Masculino , Manipulação Ortopédica , Pessoa de Meia-Idade , Exame Físico , Valor Preditivo dos Testes , Estudos Prospectivos , Amplitude de Movimento Articular , Lesões do Manguito Rotador , Sensibilidade e Especificidade , Ombro/fisiopatologia , Ombro/cirurgiaRESUMO
BACKGROUND: Popliteal arterial injuries carry a high risk of amputation. The currently available literature from both civilian and military experiences is characterized by a wide variation of recommendations for surgical management. We questioned how these recommendations have been applied in our practice. Therefore, we aimed to identify predictors of amputation after popliteal arterial injury. METHODS: We conducted an observational study of 175 patients with popliteal arterial injuries who underwent surgical treatment from 1992 to 2006 at a level I trauma center in Cali, Colombia. Information on demographic characteristics, clinical information, and surgical management was collected from clinical records. The outcome measure was amputation within 30 days following the first surgical intervention. RESULTS: The amputation rate was 17.1%. A multivariable logistic regression model indicates that blunt mechanism (odds ratio [OR] 4.79, 95% confidence interval [CI] 1.49-15.42), signs of ischemia (OR 5.29, 95% CI 1.48-18.91), ligation of the popliteal vein of the compromised limb during surgical exploration (OR 3.83, 95% CI 1.20-12.18), and the development of arterial thrombosis (OR 56.51, 95% CI 12.36-258) were found to be independent predictors of amputation. Fractures, popliteal venous injuries, prolonged time between injury and surgery, fasciotomies, and graft arterial repair were not statistically significant predictors of amputation. CONCLUSIONS: Emphasis on the early assessment and prompt identification of signs of ischemia after popliteal arterial injury continue to be the most important factor for reducing the risk of amputation, especially in blunt trauma. Vascular trauma teams must emphasize the need for the specialized management of popliteal veins. Clinical research is needed in order to identify means of decreasing arterial thrombosis after popliteal repair.