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1.
Data Brief ; 8: 1387-90, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27583346

RESUMO

The data presented in this article are related to the article entitled "Assessing Resilience in Emerging Adulthood: The Resilience Scale (RS), Connor Davidson Resilience Scale (CD-RISC), and Scale of Protective Factors (SPF)" (Madewell and Ponce-Garcia, 2016) [1]. The data were collected from a sample of 451 college students from three universities located in the Southwestern region of the United States: 374 from a large public university and 67 from two smaller regional universities. The data from the three universities did not significantly differ in terms of demographics. The data represent participant responses on six measurements to include the Resilience Scale-25 (RS-25), Resilience Scale-14 (RS-14), Connor Davidson Resilience Scale-25 (CD-RISC-25), Connor Davidson Resilience Scale-10 (CD-RISC-10), Scale of Protective Factors-24 (SPF-24), and the Life Stressor Checklist Revised (LSC-R).

2.
Curr Cancer Drug Targets ; 11(8): 976-86, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21834757

RESUMO

In an effort to develop strategies that improve the efficacy of existing anticancer agents, we have conducted a siRNA-based RNAi screen to identify genes that, when targeted by siRNA, improve the activity of the topoisomerase I (Top1) poison camptothecin (CPT). Screening was conducted using a set of siRNAs corresponding to over 400 apoptosisrelated genes in MDA-MB-231 breast cancer cells. During the course of these studies, we identified the silencing of MAP3K7 as a significant enhancer of CPT activity. Follow-up analysis of caspase activity and caspase-dependent phosphorylation of histone H2AX demonstrated that the silencing of MAP3K7 enhanced CPT-associated apoptosis. Silencing MAP3K7 also sensitized cells to additional compounds, including CPT clinical analogs. This activity was not restricted to MDA-MB-231 cells, as the silencing of MAP3K7 also sensitized the breast cancer cell line MDA-MB-468 and HCT-116 colon cancer cells. However, MAP3K7 silencing did not affect compound activity in the comparatively normal mammary epithelial cell line MCF10A, as well as some additional tumorigenic lines. MAP3K7 encodes the TAK1 kinase, an enzyme that is central to the regulation of many processes associated with the growth of cancer cells (e.g. NF- κB, JNK, and p38 signaling). An analysis of TAK1 signaling pathway members revealed that the silencing of TAB2 also sensitizes MDA-MB-231 and HCT-116 cells towards CPT. These findings may offer avenues towards lowering the effective doses of Top1 inhibitors in cancer cells and, in doing so, broaden their application.


Assuntos
Neoplasias da Mama/terapia , Neoplasias do Colo/terapia , Resistencia a Medicamentos Antineoplásicos , MAP Quinase Quinase Quinases/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Interferência de RNA , Inibidores da Topoisomerase/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Camptotecina/farmacologia , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Feminino , Técnicas de Transferência de Genes , Terapia Genética , Humanos , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Interferente Pequeno
3.
Cell Death Differ ; 18(3): 452-64, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20885445

RESUMO

The anti-apoptotic Bcl-2 protein, which confers oncogenic transformation and drug resistance in most human cancers, including breast cancer, has recently been shown to effectively counteract autophagy by directly targeting Beclin1, an essential autophagy mediator and tumor suppressor. However, it remains unknown whether autophagy inhibition contributes to Bcl-2-mediated oncogenesis. Here, by using a loss-of-function mutagenesis study, we show that Bcl-2-mediated antagonism of autophagy has a critical role in enhancing the tumorigenic properties of MCF7 breast cancer cells independent of its anti-apoptosis activity. A Bcl-2 mutant defective in apoptosis inhibition but competent for autophagy suppression promotes MCF7 breast cancer cell growth in vitro and in vivo as efficiently as wild-type Bcl-2. The growth-promoting activity of this Bcl-2 mutant is strongly correlated with its suppression of Beclin1-dependent autophagy, leading to sustained p62 expression and increased DNA damage in xenograft tumors, which may directly contribute to tumorigenesis. Thus, the anti-autophagic property of Bcl-2 is a key feature of Bcl-2-mediated oncogenesis and may in some contexts, serve as an attractive target for breast and other cancer therapies.


Assuntos
Apoptose , Autofagia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Regulação para Baixo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1 , Neoplasias da Mama/ultraestrutura , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Dano ao DNA , Feminino , Proteínas de Choque Térmico/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Nus , Proteínas Mutantes/metabolismo , Células NIH 3T3 , Ligação Proteica , Estrutura Secundária de Proteína , Proteínas Proto-Oncogênicas c-bcl-2/química , Proteína Sequestossoma-1 , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Food Sci ; 74(4): E191-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19490324

RESUMO

The effect of pH on inactivation of Escherichia coli K12 by sonication at 100 kPa/40 degrees C, manosonication (MS) at 400 kPa/40 degrees C, thermosonication (TS) at 100 kPa/61 degrees C, and manothermosonication (MTS) at 400 kPa/61 degrees C at acoustic energy density of 3 W/mL and 6 W/mL was investigated. Five linear and nonlinear kinetic models were used to examine the inactivation kinetics. At all pH levels, the inactivation rates of E. coli K12 in a buffer by TS and MTS were significantly higher than those by sonication and MS. A 5 log reduction of E. coli K12 population by TS and MTS was achieved in 0.5 and 0.25 min, respectively. With an initial count of 10(8) CFU/mL, no colonies were detected at pH 3 after a 0.25-min MTS treatment. The lethal effect of MTS was enhanced at low pH (pHs 3 and 4), whereas at nonlethal temperature of 40 degrees C, no increased killing was observed. Regardless of pH, the treatment by MTS, TS, and MS exhibited a rapid initial reduction followed by tailing-off on the inactivation curves. The biphasic linear, log-logistic, and modified Gompertz kinetic models allowed better fitting of the inactivation data for MTS, TS, and MS treatments than the 1st-order and Weibull models. The survival counts of sonication-treated E. coli K12 at all pH levels fitted well to a 1st-order kinetic model.


Assuntos
Bebidas/microbiologia , Escherichia coli K12/crescimento & desenvolvimento , Sonicação/métodos , Contagem de Colônia Microbiana , Frutas , Temperatura Alta , Concentração de Íons de Hidrogênio , Cinética , Viabilidade Microbiana , Pressão
5.
Br J Cancer ; 98(9): 1515-24, 2008 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-18382425

RESUMO

Understanding the mechanisms of multidrug resistance (MDR) could improve clinical drug efficacy. Multidrug resistance is associated with ATP binding cassette (ABC) transporters, but the factors that regulate their expression at clinically relevant drug concentrations are poorly understood. We report that a single-step selection with low doses of anti-cancer agents, similar to concentrations reported in vivo, induces MDR that is mediated exclusively by ABCG2. We selected breast, ovarian and colon cancer cells (MCF-7, IGROV-1 and S-1) after exposure to 14 or 21 nM doxorubicin for only 10 days. We found that these cells overexpress ABCG2 at the mRNA and protein levels. RNA interference analysis confirmed that ABCG2 confers drug resistance. Furthermore, ABCG2 upregulation was facilitated by histone hyperacetylation due to weaker histone deacetylase 1-promoter association, indicating that these epigenetic changes elicit changes in ABCG2 gene expression. These studies indicate that the MDR phenotype arises following low-dose, single-step exposure to doxorubicin, and further suggest that ABCG2 may mediate early stages of MDR development. This is the first report to our knowledge of single-step, low-dose selection leading to overexpression of ABCG2 by epigenetic changes in multiple cancer cell lines.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Epigênese Genética , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Acetilação , Antineoplásicos/farmacologia , Western Blotting , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Humanos , Mitoxantrona/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , RNA Mensageiro/isolamento & purificação , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
6.
J Food Sci ; 73(2): E69-81, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18298728

RESUMO

Mold growth is a common problem during the equilibration of food materials at high relative humidity values using the standard saturated salt slurry method. Exposing samples to toluene vapor and mixing samples with mold inhibitor chemicals are suggested methods for preventing mold growth while obtaining isotherms. However, no published research was found that examined the effect of mold growth on isotherm performance or the efficacy of various mold inhibitor methods, including their possible effect on the physicochemical properties of food materials. Therefore, the objectives of this study were to (1) explore the effect of mold growth on isotherm performance in a range of food materials, (2) investigate the effectiveness of 4 mold inhibitor methods, irradiation, 2 chemical inhibitors (potassium sorbate and sodium acetate), and toluene vapor, on mold growth on dent corn starch inoculated with A. niger, and (3) examine the effect of mold inhibitor methods on the physicochemical properties of dent corn starch, including isotherm performance, pasting properties, gelatinization temperature, and enthalpy. Mold growth was found to affect starch isotherm performance by contributing to weight changes during sample equilibration. Among the 4 mold inhibitor methods tested, irradiation and toluene vapor were found to be the most effective for inhibiting growth of A. niger on dent cornstarch. However, both methods exhibited a significant impact on the starches' physiochemical properties, suggesting the need to probe the efficacy of other mold inhibitor methods and explore the use of new rapid isotherm instruments, which hamper mold growth by significantly decreasing measurement time.


Assuntos
Antifúngicos/farmacologia , Aspergillus niger/crescimento & desenvolvimento , Contaminação de Alimentos/prevenção & controle , Conservação de Alimentos/métodos , Zea mays/microbiologia , Adsorção , Contaminação de Alimentos/análise , Manipulação de Alimentos/métodos , Irradiação de Alimentos , Microbiologia de Alimentos , Tecnologia de Alimentos/métodos , Humanos , Umidade , Amido , Termodinâmica , Fatores de Tempo , Tolueno/farmacologia , Zea mays/química
7.
QJM ; 100(6): 361-7, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17525132

RESUMO

BACKGROUND: Predictive equations have been proposed as a simpler alternative to hypoxic challenge testing (HCT) for determining the risk of in-flight hypoxia. AIM: To assess agreement between hypoxic challenge testing (HCT) and predictive equations for assessment of in-flight hypoxia. DESIGN: Retrospective study. METHODS: Patients with chronic obstructive pulmonary disease (COPD) (n = 15), interstitial lung disease (ILD) (n = 15) and cystic fibrosis (CF) (n = 15) were studied. Spirometry was recorded prior to hypoxic inhalation and oxygen saturations (SpO2) were recorded before, after and during hypoxic inhalation. Blood gases were analysed before and after hypoxic inhalation and when SpO2 = 85%. An HCT was performed using the Ventimask method. The PaO2 at altitude was estimated for each group using four published predictive equations, which use values of PaO2 (ground) and lung function measurements to predict altitude PaO2. Results were interpreted using the BTS recommendations for prescription of in-flight oxygen post HCT. The Stuart Maxwell test of overall homogeneity was used to assess agreement between HCT results and each of the predictive equations. RESULTS: Ground PaO2 was significantly greater in patients with CF than either ILD or COPD (p < 0.05). PaO2 in all three groups significantly decreased following HCT. With the exception of equation 3, significantly fewer patients in each group would require in-flight O2 if prescription was based on HCT, compared to predictive equations (p < 0.05). DISCUSSION: Predictive equations considerably overestimate the need for in-flight O2, compared to HCT.


Assuntos
Fibrose Cística/fisiopatologia , Hipóxia/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Medicina Aeroespacial/métodos , Pressão do Ar , Aeronaves , Fibrose Cística/sangue , Feminino , Previsões/métodos , Humanos , Hipóxia/sangue , Doenças Pulmonares Intersticiais/sangue , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Doença Pulmonar Obstrutiva Crônica/sangue , Estudos Retrospectivos , Espirometria , Viagem
8.
Rev Latinoam Microbiol ; 48(3-4): 260-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-18293660

RESUMO

This work was conducted to identify indigenous LAB capable of antimicrobial activity, present in traditional Mexican-foods with potential as natural preservatives. A total of 27 artisan unlabeled Mexican products were evaluated, from which 94 LAB strains were isolated, and only 25 strains showed antimicrobial activity against at least one pathogen indicator microorganism. Most of the inhibitory activity showed by the isolated LAB strains was attributed to pH reduction by organic acids. Lactobacillus and Lactococcus strains were good acid producers, depending on the substrate, and may enhance the safety of food products. Cell free cultures of Leuconostoc mesenteroides CH210, and PT8 (from chorizo and pulque, respectively) reduced the number of viable cells of enteropathogenic E. coli in broth system. Lb. plantarum CC10 (from "madre" of vinegar) showed significant inhibitory effect against S. aureus 8943. E. faecium QPII (from panela cheese) produced a bacteriocin with wide anti-L. monocytogenes activity. Selected LAB from traditional Mexican foods showed good potential as bio-preservatives.


Assuntos
Ácidos/metabolismo , Anti-Infecciosos/metabolismo , Bacteriocinas/metabolismo , Microbiologia de Alimentos , Lactobacillus/isolamento & purificação , Lactococcus/isolamento & purificação , Leuconostoc/isolamento & purificação , Bebidas Alcoólicas/microbiologia , Queijo/microbiologia , Meios de Cultivo Condicionados/farmacologia , Manipulação de Alimentos/métodos , Conservação de Alimentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Lactobacillus/metabolismo , Lactococcus/metabolismo , Leuconostoc/metabolismo , Produtos da Carne/microbiologia , México , Testes de Sensibilidade Microbiana
9.
Curr Microbiol ; 51(2): 110-5, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15991053

RESUMO

Artisan fresh Mexican-style cheeses are commonly made from raw milk that provides not only rich flavors, but also a diversity of associated lactic acid bacteria (LAB) strains. Enterococcus faecium UQ31 was isolated from panela cheese and produced bacteriocin-like inhibitory substances (BLIS) with a strong anti-Listeria activity. A modified pH-mediated adsorption-desorption purification process resulted in (after SDS-PAGE) two bands showing antimicrobial activities, where most of the activity corresponded to the band with an estimated molecular weight of 7.5 kDa. The BLIS produced by E. faecium UQ31 were heat resistant, stable at ambient storage conditions, and active in the pH range 5--9. The BLIS antimicrobial activities were detected during logarithmic growth phase and remained constant until the end of incubation time (19 h). These BLIS showed a wide anti-Listeria monocytogenes spectra. The E. faecium UQ31 strain or their BLIS represent a promising potential as antimicrobial food preservatives.


Assuntos
Bacteriocinas/isolamento & purificação , Bacteriocinas/farmacologia , Enterococcus faecium/metabolismo , Microbiologia de Alimentos , Listeria monocytogenes/efeitos dos fármacos , Animais , Bacteriocinas/biossíntese , Queijo/microbiologia , Estabilidade de Medicamentos , Leite/microbiologia
12.
Alcohol Res Health ; 25(1): 72-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11496970

RESUMO

Data collected in the Arrestee Drug Abuse Monitoring (ADAM) program on alcohol and other drug use among arrestees provide a valuable opportunity to examine the relationship between alcohol use and violence. The data are used to explore the combined use of alcohol and other drugs among offenders and the relationships between substance use and the offenders' demographic characteristics and offenses. These findings are used to identify changes in the offenders' alcohol and other drug use over time.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Crime/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/psicologia , Feminino , Humanos , Drogas Ilícitas , Masculino , Pessoa de Meia-Idade , Autoavaliação (Psicologia) , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estados Unidos/epidemiologia
13.
Am J Addict ; 10(2): 136-58, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11444156

RESUMO

Many studies indicate that alcohol abuse and dependence are closely linked with the criminal justice system (CJS). Alcohol was consumed prior to about half of all homicides and assaults, and nearly 40 percent of state prisoners report committing their current offense under the influence of alcohol. Alcohol abuse cost approximately $13 billion in 1992 non-health related costs. This article seeks to address this burden on the CJS and society. It presents a conceptual framework for explaining the alcohol-crime nexus, reviews empirical evidence of the complex associations between alcohol consumption and crime, and links these with promising intervention strategies to reduce alcohol-related crime.


Assuntos
Alcoolismo/epidemiologia , Crime , Direito Penal , Adulto , Alcoolismo/prevenção & controle , Terapia Cognitivo-Comportamental , Relações Comunidade-Instituição , Crime/prevenção & controle , Crime/estatística & dados numéricos , Feminino , Humanos , Masculino
14.
J Subst Abuse ; 13(4): 563-81, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11775083

RESUMO

PURPOSE: To explore the associations between violent and other crimes, and alcohol intoxication and recent use of cocaine, marijuana, and other drugs among men and women arrestees and examine gender differences in these relationships. METHODS: We conducted a secondary analysis of 1998 using Arrestee Drug Abuse Monitoring (ADAM) system data using a sample of 9242 male and 2594 women arrested for violent and property offenses in 35 cities. Logistic regression was used to predict arrest for a violent offense (rather than a property crime) from drug- and alcohol-related, and other variables. RESULTS: Both gender and alcohol intoxication are significantly related to arrest for a violent offense. However, the intoxication effects (in the absence of cocaine) are more than three times as great for female (Exp(beta) = 5.59) as male arrestees (Exp(beta) = 1.74), while the combined effects of alcohol and cocaine predict a property offense for women but are insignificant for men. IMPLICATIONS: To achieve further reductions in violent crime, intervention strategies need to focus on reducing alcohol intoxication as well as illicit drug use. Research on the role of alcohol on women's aggression and violence also is suggested.


Assuntos
Intoxicação Alcoólica/psicologia , Drogas Ilícitas , Prisioneiros/psicologia , Detecção do Abuso de Substâncias , Adulto , Intoxicação Alcoólica/epidemiologia , Intoxicação Alcoólica/urina , Alcoolismo/urina , Crime , Feminino , Humanos , Drogas Ilícitas/urina , Masculino , Prisioneiros/estatística & dados numéricos , Distribuição por Sexo , Detecção do Abuso de Substâncias/estatística & dados numéricos , Estados Unidos/epidemiologia , Violência
15.
Anal Chem ; 72(18): 4266-74, 2000 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-11008759

RESUMO

Subfemtomole peptide sequence analysis has been achieved using microcapillary HPLC columns, with integrated nanoelectrospray emitters, coupled directly to a Fourier transform ion cyclotron resonance mass spectrometer. Accurate mass (+/-0.010 Da) peptide maps are generated from a standard six-protein digest mixture, whose principle components span a concentration dynamic range of 1000:1. Iterative searches against approximately 189000 entries in the OWL database readily identify each protein, with high sequence coverage (20-60%), from as little as 10 amol loaded on-column. In addition, a simple variable-flow HPLC apparatus provides for on-line tandem mass spectrometric analysis of tryptic peptides at the 400-amol level. MS/MS data are searched against approximately 280000 entries in a nonredundant protein database using SEQUEST. Accurate precursor and product ion mass information readily identifies primary amino acid sequences differing by asparagine vs aspartic acid (deltam = 0.98 Da) and glutamine vs lysine (deltam = 0.036 Da).


Assuntos
Peptídeos/análise , Algoritmos , Sequência de Aminoácidos , Animais , Cromatografia Líquida de Alta Pressão , Ciclotrons , Análise de Fourier , Dados de Sequência Molecular , Proteínas Musculares/química , Mapeamento de Peptídeos , Coelhos , Análise de Sequência , Espectrometria de Massas por Ionização por Electrospray
16.
Am J Hematol ; 65(2): 141-8, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10996832

RESUMO

Bernard-Soulier syndrome (BSs) is a rare bleeding disorder characterized by circulating giant platelets, thrombocytopenia, and a prolonged bleeding time. BSs usually has an autosomal recessive inheritance pattern, with a preponderance of Caucasian and Japanese ancestry when the ethnic background has been reported. Underlying this disorder of platelet function is a defect in the platelet glycoprotein (GP) Ib-IX-V complex, composed of four polypeptides, GP Ib alpha, GP Ib beta, GP IX, and GP V. Molecular characterization of individuals with BSs has identified mutations in the GP Ib alpha, GP Ib beta, and GP IX genes responsible for the expressed phenotype. In this study, we report a family of African-American descent, with autosomal recessive BSs showing a point mutation in codon 129 of the GP Ib alpha gene. This mutation, CTC:wild-type to CCC:mutant, is similar to that of another African American family where the resulting leucine to proline substitution in the 5(th) leucine-rich repeat of GP Ib alpha is responsible for the observed BSs phenotype. Comparison of the intragenic polymorphisms of GP Ib alpha, as well as microsatellite markers in a 17.5 cM region of chromosome 17p12 that contains the GP Ib alpha gene, suggests that, although socially unrelated, the Leu129Pro mutation in these two families has a common founder.


Assuntos
Síndrome de Bernard-Soulier/genética , África/etnologia , População Negra/genética , Cromossomos Humanos Par 17 , Sequência Consenso , Análise Mutacional de DNA , Saúde da Família , Feminino , Homozigoto , Humanos , Repetições de Microssatélites , Pessoa de Meia-Idade , Linhagem , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Mutação Puntual/genética , Polimorfismo Genético/genética , Estados Unidos
17.
Mol Cell Neurosci ; 16(2): 141-56, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10924257

RESUMO

The POU domain transcription factor Brn-3b (also called Brn-3.2) is essential for the normal development of retinal ganglion cells (RGCs) in the mouse. Without Brn-3b, RGCs commit to their fate and migrate to the ganglion cell layer, but most cells die during fetal development. An earlier report (L. Gan et al., 1999, Dev. Biol. 210, 469-480) suggested that cell death was caused by abnormal axon formation. Here, we use retinal explants from wild-type and mutant embryos to show that brn-3b-deficient RGCs are not properly polarized and tend to form dendrites rather than axons. Compared with wild-type explants, neurites of RGCs from brn-3b-deficient retinal explants grew slower, were shorter, and did not fasciculate properly. Mutant neurites had more microtubules than wild-type controls, and the arrangement of microtubules and neurofilaments was characteristic of dendrites rather than axons. Neurites from individual mutant RGCs displayed abnormal polarity and had dendrite-like branches extending outward from their main axis. Most mutant RGCs exhibited abnormal migratory behavior, and their neurites labeled intensely with the dendrite marker MAP-2. A small number of mutant RGCs were not migratory, and their neurites were longer and labeled positively for the axon marker tau-1, suggesting that some RGCs were not as severely affected by the absence of Brn-3b as others. Although tau-1 was not observed in most mutant neurites, it did accumulate in mutant cell bodies, implying that the absence of Brn-3b caused a defect in axon transport. Thus, Brn-3b appears to control the activity of genes that function in establishing RGC polarity, and without Brn-3b, RGCs cannot extend normal axons.


Assuntos
Axônios/fisiologia , Polaridade Celular/fisiologia , Proteínas de Ligação a DNA/genética , Células Ganglionares da Retina/ultraestrutura , Fatores de Transcrição/genética , Animais , Axônios/química , Células Cultivadas , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/química , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica , Proteínas Associadas aos Microtúbulos/análise , Proteínas Associadas aos Microtúbulos/genética , Microtúbulos/genética , Neuritos/fisiologia , Proteínas de Neurofilamentos/fisiologia , Fatores do Domínio POU , Estrutura Terciária de Proteína , Células Ganglionares da Retina/química , Fator de Transcrição Brn-3 , Fator de Transcrição Brn-3B , Fatores de Transcrição/análise , Fatores de Transcrição/química , Proteínas tau/análise , Proteínas tau/genética
18.
Sleep ; 23 Suppl 4: S102-8, 2000 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-10893080

RESUMO

The magnitude, determinants and reversibility of cognitive deficits associated with the sleep apnea/hypopnea syndrome (SAHS) are of clinical and research interest. A quantitative overview of impairment effect sizes (ESs) from case-control studies of cognitive performance in SAHS suggests that deficits broadly worsen with disease severity, with large average values for attentional (ES approximately 1.0 SD units) and executive (ES approximately 0.9 SD units) cognitive scores, and moderate values for memory-related (ES approximately 0.6 SD units) performance scores. A study of determinants of cognitive outcomes conducted in 150 patients with SAHS (AHI 5+ and > or =2 symptoms) showed significant but weak associations between a cognitive 'intellectual ability' component score (CS) and both AHI (r=-0.14) and minimum oxygen saturation (r = 0.15), linking increasing disease severity with poorer performance. A somewhat stronger correlation between a cognitive 'response slowing' CS and a 'wakefulness' CS was observed (r=-0.34). That sleepiness as well as hypoxemia might contribute to cognitive deficit has also been suggested by experimental sleep fragmentation in normals, producing small to moderate impairments (average ES approximately 0.3 SD units) in attention-biased scores. The reversibility of attentional cognitive deficits has been investigated through a meta-analysis of randomized placebo-controlled crossover studies of CPAP treatment, involving 98 SAHS patients (AHI 5+ and > or =2 symptoms). While cognitive outcomes showed at least trends towards better performance on CPAP than on placebo (p< or =0.1), the ESs of cognitive enhancements following CPAP were small (average ES approximately 0.2 SD units). This may be due either to the relatively mild study population, suboptimal CPAP use or to an irreversible component in cognitive impairment in SAHS.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Síndromes da Apneia do Sono/complicações , Estudos de Casos e Controles , Estudos Cross-Over , Eletroencefalografia , Humanos , Metanálise como Assunto , Testes Neuropsicológicos , Respiração com Pressão Positiva/métodos , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/terapia , Vigília/fisiologia
19.
Diagn Cytopathol ; 23(1): 46-50, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10907933

RESUMO

Metaplastic carcinomas of the breast are uncommon breast tumors with aberrant cellular differentiation, most commonly showing ductal, squamous, and mesenchymal components. A breast carcinoma composed of both epithelial and melanocytic differentiation is rare, with only four previously reported cases in the literature. We present the fifth reported case, where the diagnosis was suggested by fine-needle aspiration (FNA) and later confirmed after the surgical specimen was excised. Histologically, this neoplasm revealed multidirectional differentiation, consisting primarily of squamous and melanocytic cell types, with focal glandular and osseous metaplasia. Based on the morphologic, immunohistochemical, and ultrastructural findings, we conclude that such tumors fall within the spectrum of metaplastic carcinomas of the breast. We believe that this case will further contribute to the understanding of this enigmatic tumor.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Adenoescamoso/patologia , Carcinoma Ductal de Mama/patologia , Antígenos de Neoplasias , Biópsia por Agulha , Mama/química , Mama/patologia , Mama/ultraestrutura , Neoplasias da Mama/química , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Carcinoma Adenoescamoso/química , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/cirurgia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/cirurgia , Diferenciação Celular , Feminino , Humanos , Imuno-Histoquímica/métodos , Metástase Linfática , Mastectomia Radical Modificada , Melanócitos/química , Melanócitos/citologia , Melanoma/diagnóstico , Melanoma/patologia , Antígenos Específicos de Melanoma , Melanossomas , Microscopia Eletrônica/métodos , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Proteínas S100/análise
20.
Proc Natl Acad Sci U S A ; 97(9): 4742-7, 2000 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-10758156

RESUMO

To investigate the role of the Fhit gene in carcinogen induction of neoplasia, we have inactivated one Fhit allele in mouse embryonic stem cells and produced (129/SvJ x C57BL/6J) F(1) mice with a Fhit allele inactivated (+/-). Fhit +/+ and +/- mice were treated intragastrically with nitrosomethylbenzylamine and observed for 10 wk posttreatment. A total of 25% of the +/+ mice developed adenoma or papilloma of the forestomach, whereas 100% of the +/- mice developed multiple tumors that were a mixture of adenomas, squamous papillomas, invasive carcinomas of the forestomach, as well as tumors of sebaceous glands. The visceral and sebaceous tumors, which lacked Fhit protein, were similar to those characteristic of Muir-Torre familial cancer syndrome.


Assuntos
Hidrolases Anidrido Ácido , Neoplasias Primárias Múltiplas/genética , Proteínas/genética , Adenoma/genética , Animais , Carcinógenos , Dimetilnitrosamina/análogos & derivados , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Proteínas de Neoplasias/deficiência , Proteínas de Neoplasias/genética , Neoplasias Primárias Múltiplas/induzido quimicamente , Neoplasias Primárias Múltiplas/patologia , Papiloma/genética , Proteínas/metabolismo , Mapeamento por Restrição , Neoplasias das Glândulas Sebáceas/genética , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Síndrome
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