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1.
J Intern Med ; 287(3): 283-300, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31677303

RESUMO

Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a concerning global pathogen. hvKp is more virulent than classical K. pneumoniae (cKp) and capable of causing community-acquired infections, often in healthy individuals. hvKp is carried in the gastrointestinal tract, which contributes to its spread in the community and healthcare settings. First recognized in Asia, hvKp arose as a leading cause of pyogenic liver abscesses. In the decades since, hvKp has spread globally and causes a variety of infections. In addition to liver abscesses, hvKp is distinct from cKp in its ability to metastasize to distant sites, including most commonly the eye, lung and central nervous system (CNS). hvKp has also been implicated in primary extrahepatic infections including bacteremia, pneumonia and soft tissue infections. The genetic determinants of hypervirulence are often found on large virulence plasmids as well as chromosomal mobile genetic elements which can be used as biomarkers to distinguish hvKp from cKp clinical isolates. These distinct virulence determinants of hvKp include up to four siderophore systems for iron acquisition, increased capsule production, K1 and K2 capsule types, and the colibactin toxin. Additionally, hvKp strains demonstrate hypermucoviscosity, a phenotypic description of hvKp in laboratory conditions that has become a distinguishing feature of many hypervirulent isolates. Alarmingly, multidrug-resistant hypervirulent strains have emerged, creating a new challenge in combating this already dangerous pathogen.


Assuntos
Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/patogenicidade , Virulência , Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/epidemiologia , Farmacorresistência Bacteriana , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos
2.
Scand J Med Sci Sports ; 24(4): 678-82, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23346987

RESUMO

We aimed to determine whether a unique, ultra-high-field 7 T magnetic resonance imaging (MRI) scanner could detect occult cartilage and meniscal injuries in asymptomatic female dancers. This study had Institutional Review Board approval. We recruited eight pre-professional female dancers and nine non-athletic, female controls. We scanned the dominant knee on a 7 T MRI scanner using a three-dimensional fast low-angle shot sequence and a proton density, fast spin-echo sequence to evaluate cartilage and menisci, respectively. Two radiologists scored cartilage (International Cartilage Repair Society classification) and meniscal (Stoller classification) lesions. We applied two-tailed z- and t-tests to determine statistical significance. There were no cartilage lesions in dancers or controls. For the medial meniscus, the dancers demonstrated higher mean MRI score (2.38 ± 0.61 vs 1.0 ± 0.97, P < 0.0001) and higher frequency of mean grade 2 lesions (88% vs 11%, P < 0.01) compared with the controls. For the lateral meniscus, there was no difference in score (0.5 ± 0.81 vs 0.5 ± 0.78, P = 0.78) in dancers compared with the control groups. Asymptomatic dancers demonstrate occult medial meniscal lesions. Because this has been described in early osteoarthritis, close surveillance of dancers' knee symptoms and function with appropriate activity modification may help maintain their long-term knee health.


Assuntos
Dança/lesões , Imageamento por Ressonância Magnética/métodos , Lesões do Menisco Tibial , Adulto , Doenças Assintomáticas , Feminino , Humanos , Traumatismos do Joelho/diagnóstico , Adulto Jovem
3.
Osteoporos Int ; 24(4): 1407-17, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22893356

RESUMO

UNLABELLED: Micro-finite element analysis applied to high-resolution (0.234-mm length scale) MRI reveals greater whole and cancellous bone stiffness, but not greater cortical bone stiffness, in the distal femur of female dancers compared to controls. Greater whole bone stiffness appears to be mediated by cancellous, rather than cortical bone adaptation. INTRODUCTION: The purpose of this study was to compare bone mechanical competence (stiffness) in the distal femur of female dancers compared to healthy, relatively inactive female controls. METHODS: This study had institutional review board approval. We recruited nine female modern dancers (25.7±5.8 years, 1.63±0.06 m, 57.1±4.6 kg) and ten relatively inactive, healthy female controls matched for age, height, and weight (32.1±4.8 years, 1.6±0.04 m, 55.8±5.9 kg). We scanned the distal femur using a 7-T MRI scanner and a three-dimensional fast low-angle shot sequence (TR/TE=31 ms/5.1 ms, 0.234 mm×0.234 mm×1 mm, 80 slices). We applied micro-finite element analysis to 10-mm-thick volumes of interest at the distal femoral diaphysis, metaphysis, and epiphysis to compute stiffness and cross-sectional area of whole, cortical, and cancellous bone, as well as cortical thickness. We applied two-tailed t-tests and ANCOVA to compare groups. RESULTS: Dancers demonstrated greater whole and cancellous bone stiffness and cross-sectional area at all locations (p<0.05). Cortical bone stiffness, cross-sectional area, and thickness did not differ between groups (>0.08). At all locations, the percent of intact whole bone stiffness for cortical bone alone was lower in dancers (p<0.05). Adjustment for cancellous bone cross-sectional area eliminated significant differences in whole bone stiffness between groups (p>0.07), but adjustment for cortical bone cross-sectional area did not (p<0.03). CONCLUSIONS: Modern dancers have greater whole and cancellous bone stiffness in the distal femur compared to controls. Elevated whole bone stiffness in dancers may be mediated via cancellous, rather than cortical bone adaptation.


Assuntos
Dança/fisiologia , Fêmur/fisiologia , Adulto , Fenômenos Biomecânicos , Estudos de Casos e Controles , Diáfises/anatomia & histologia , Diáfises/fisiologia , Elasticidade/fisiologia , Epífises/anatomia & histologia , Epífises/fisiologia , Feminino , Fêmur/anatomia & histologia , Análise de Elementos Finitos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adulto Jovem
4.
Cell Death Differ ; 19(10): 1709-21, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22555457

RESUMO

The inflammasome is a signalling platform leading to caspase-1 activation. Caspase-1 causes pyroptosis, a necrotic-like cell death. AIM2 is an inflammasome sensor for cytosolic DNA. The adaptor molecule ASC mediates AIM2-dependent caspase-1 activation. To date, no function besides caspase-1 activation has been ascribed to the AIM2/ASC complex. Here, by comparing the effect of gene inactivation at different levels of the inflammasome pathway, we uncovered a novel cell death pathway activated in an AIM2/ASC-dependent manner. Francisella tularensis, the agent of tularaemia, triggers AIM2/ASC-dependent caspase-3-mediated apoptosis in caspase-1-deficient macrophages. We further show that AIM2 engagement leads to ASC-dependent, caspase-1-independent activation of caspase-8 and caspase-9 and that caspase-1-independent death is reverted upon caspase-8 inhibition. Caspase-8 interacts with ASC and active caspase-8 specifically colocalizes with the AIM2/ASC speck thus identifying the AIM2/ASC complex as a novel caspase-8 activation platform. Furthermore, we demonstrate that caspase-1-independent apoptosis requires the activation of caspase-9 and of the intrinsic pathway in a typical type II cell manner. Finally, we identify the AIM2/ASC-dependent caspase-1-independent pathway as an innate immune mechanism able to restrict bacterial replication in vitro and control IFN-γ levels in vivo in Casp1(KO) mice. This work underscores the crosstalk between inflammasome components and the apoptotic machinery and highlights the versatility of the pathway, which can switch from pyroptosis to apoptosis.


Assuntos
Apoptose , Proteínas do Citoesqueleto/metabolismo , Francisella tularensis/patogenicidade , Macrófagos/metabolismo , Proteínas Nucleares/metabolismo , Animais , Proteínas Reguladoras de Apoptose , Proteínas Adaptadoras de Sinalização CARD , Caspase 1/deficiência , Caspase 1/genética , Caspase 1/metabolismo , Caspase 3/metabolismo , Caspase 8/metabolismo , Células Cultivadas , Citocinas/metabolismo , Proteínas do Citoesqueleto/deficiência , Proteínas do Citoesqueleto/genética , Proteínas de Ligação a DNA , Células HEK293 , Humanos , Inflamassomos/metabolismo , Camundongos , Camundongos Knockout , Tularemia/metabolismo , Tularemia/microbiologia , Tularemia/patologia
5.
AIDS Behav ; 16(8): 2160-70, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22426597

RESUMO

Trauma and posttraumatic stress disorder disproportionally affect HIV-positive women. Studies increasingly demonstrate that both conditions may predict poor HIV-related health outcomes and transmission-risk behaviors. This study analyzed data from a prevention-with-positives program to understand if socio-economic, behavioral, and health-related factors are associated with antiretroviral failure and HIV transmission-risk behaviors among 113 HIV-positive biological and transgender women. An affirmative answer to a simple screening question for recent trauma was significantly associated with both outcomes. Compared to participants without recent trauma, participants reporting recent trauma had over four-times the odds of antiretroviral failure (AOR 4.3; 95% CI 1.1-16.6; p = 0.04), and over three-times the odds of reporting sex with an HIV-negative or unknown serostatus partner (AOR 3.9; 95% CI 1.3-11.9; p = 0.02) and <100% condom use with these partners (AOR 4.5; 95% CI 1.5-13.3; p = 0.007). Screening for recent trauma in HIV-positive biological and transgender women identifies patients at high risk for poor health outcomes and HIV transmission-risk behavior.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Transtornos de Estresse Pós-Traumáticos/psicologia , Pessoas Transgênero/psicologia , Violência/psicologia , Adulto , Idoso , California , Preservativos/estatística & dados numéricos , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/psicologia , Inquéritos Epidemiológicos , Humanos , Entrevistas como Assunto , Modelos Logísticos , Adesão à Medicação , Saúde Mental , Pessoa de Meia-Idade , Fatores de Risco , Assunção de Riscos , Comportamento Sexual/psicologia , Parceiros Sexuais , Fatores Socioeconômicos , Inquéritos e Questionários , Falha de Tratamento , Adulto Jovem
6.
AIDS Behav ; 16(8): 2091-100, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22249954

RESUMO

Women bear an increasing burden of the HIV epidemic and face high rates of morbidity and mortality. Trauma has been increasingly associated with the high prevalence and poor outcomes of HIV in this population. This meta-analysis estimates rates of psychological trauma and posttraumatic stress disorder (PTSD) in HIV-positive women from the United States. We reviewed 9,552 articles, of which 29 met our inclusion criteria, resulting in a sample of 5,930 individuals. The findings demonstrate highly disproportionate rates of trauma exposure and recent PTSD in HIV-positive women compared to the general population of women. For example, the estimated rate of recent PTSD among HIV-positive women is 30.0% (95% CI 18.8-42.7%), which is over five-times the rate of recent PTSD reported in a national sample of women. The estimated rate of intimate partner violence is 55.3% (95% CI 36.1-73.8%), which is more than twice the national rate. Studies of trauma-prevention and trauma-recovery interventions in this population are greatly needed.


Assuntos
Infecções por HIV/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Violência/psicologia , Feminino , Infecções por HIV/diagnóstico , Humanos , Relações Interpessoais , Prevalência , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estados Unidos/epidemiologia , Violência/estatística & dados numéricos
7.
Br J Pharmacol ; 153(5): 1062-71, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18204487

RESUMO

BACKGROUND AND PURPOSE: This study investigated the alpha(1)beta(2)delta isoform of the GABA(A) receptor that is presumably expressed in the forebrain. The functional and pharmacological properties of this receptor combination are largely unknown. EXPERIMENTAL APPROACH: We expressed alpha(1)beta(2)delta GABA(A) receptors in Xenopus laevis oocytes. GABA-activated currents, in the presence and absence of modulators, were recorded using the two-electrode voltage clamp technique. KEY RESULTS: The alpha(1)beta(2)delta isoform of the GABA(A) receptor exhibited an extremely small GABA-mediated current. Tracazolate increased the current amplitude evoked by a half-maximal concentration (EC(50)) of GABA by 59-fold. The maximum current was increased 23-fold in the presence of a saturating GABA concentration. Concomitant with the increase in the maximum, was a 4-fold decrease in the EC(50). Finally, a mutation in the second transmembrane domain of the delta subunit that increases receptor efficacy (L286S), eliminated the increase in the maximum GABA-activated current. The endogenous neurosteroid, tetrahydrodeoxycorticosterone (THDOC), also decreased the EC(50) and increased the maximum current amplitude, although to a lesser degree than that of tracazolate. CONCLUSIONS AND IMPLICATIONS: Taken all together, these findings indicate that the small GABA-mediated currents in the absence of the modulator are due to a low efficacy for activation. In the absence of modulators, alpha(1)beta(2)delta GABA receptors would be effectively silent and therefore contribute little to inhibition in the CNS. In the presence of tracazolate or endogenous neurosteroids however, this particular receptor isoform could exert a profound inhibitory influence on neuronal activity.


Assuntos
Desoxicorticosterona/análogos & derivados , Expressão Gênica , Pirazóis/farmacologia , Receptores de GABA-A/metabolismo , Animais , Desoxicorticosterona/farmacologia , Relação Dose-Resposta a Droga , Eletrofisiologia , Oócitos , Técnicas de Patch-Clamp , Isoformas de Proteínas , Subunidades Proteicas , Ratos , Receptores de GABA-A/efeitos dos fármacos , Xenopus laevis , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/farmacologia
8.
J Physiol ; 548(Pt 2): 527-40, 2003 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-12626678

RESUMO

An important feature of ligand-gated ion channels is their exquisite ability to discriminate between ions. Still, little is known about the mechanisms underlying, or structural determinates of, this ability. We examined the structural elements underlying the ionic selectivity of rho1 GABA receptors expressed in Xenopus oocytes and human embryonic kidney cells using site-directed mutagenesis and two-electrode voltage-clamp or patch-clamp techniques. The wild-type GABA receptor was chloride selective, with a small but significant permeability to potassium (PNa+ : PK+ : PCl- = 0 : 0.03 :1). Mutation of an alanine to glutamate at position 291 (thought to be located at the intracellular end of the second transmembrane domain), formed a channel that exhibited little discrimination among ions (0.70:0.87:1), while deletion of a neighbouring proline (290) was chloride selective, but had elevated cation permeabilities compared to the wild-type channel (0.12 : 0.14 : 1). Together, the two mutations (DeltaP290/A291E) caused a reversal of selectivity (2.72 : 3.59 : 1). We also examined the effects of neutralizing and reversing the charge of the adjacent, and highly conserved, arginine. Mutation of the neighbouring arginine to glutamate (R292E) increased the cation permeability similar to the DeltaP290/A291E double mutant (2.4 : 3.0 : 1), whereas neutral mutations at this position (R292M or R292C) retained chloride selectivity (0 : 0.11 : 1.0 and 0 : 0.14 : 1.0, respectively). Our experiments suggest that the effective charge near the presumed intracellular mouth of the pore is critical for ionic selectivity.


Assuntos
Mutação/fisiologia , Receptores de GABA/genética , Receptores de GABA/fisiologia , Algoritmos , Sequência de Aminoácidos , Animais , Cálcio/metabolismo , Linhagem Celular , Cloretos/metabolismo , DNA Complementar/biossíntese , DNA Complementar/genética , Eletrofisiologia , Humanos , Canais Iônicos/efeitos dos fármacos , Canais Iônicos/metabolismo , Cinética , Fígado/citologia , Fígado/metabolismo , Potenciais da Membrana/fisiologia , Microinjeções , Dados de Sequência Molecular , Oócitos/fisiologia , Técnicas de Patch-Clamp , Transcrição Gênica/genética , Xenopus laevis
9.
Biol Psychiatry ; 50(12): 952-9, 2001 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11750891

RESUMO

BACKGROUND: Previous magnetic resonance imaging studies of posttraumatic stress disorder reported hippocampal volume loss. The goals of this study were 1) to determine the relationship between hippocampal atrophy and posttraumatic stress disorder in the absence of alcohol abuse, and 2) to test if loss of N-acetylaspartate (a neuron marker) in the hippocampus of posttraumatic stress disorder occurs separate from atrophy. In addition, volume changes in the entorhinal cortex were also explored. METHODS: Eighteen male patients with combat-related posttraumatic stress disorder (mean age 51.2 +/- 2.5 years) and 19 male control subjects (mean age 51.8 +/- 3.2 years) were studied using magnetic resonance imaging and Proton magnetic resonance spectroscopic imaging. Both groups had no alcohol and drug abuse during the past 5 years. RESULTS: Posttraumatic stress disorder and control subjects had similar volumes of hippocampus and entorhinal cortex. In contrast to volume, N-acetylaspartate was significantly reduced by about 23% bilaterally in the hippocampus of posttraumatic stress disorder when compared with control subjects, and creatine-containing compounds were reduced by 26% in the right hippocampus of posttraumatic stress disorder. CONCLUSIONS: N-acetyl asparate and creatine reductions imply that there are hippocampal abnormalities in posttraumatic stress disorder. Furthermore, these metabolite changes seem to be better indicators of posttraumatic stress disorder pathology than volume losses.


Assuntos
Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Creatina/metabolismo , Hipocampo/metabolismo , Espectroscopia de Ressonância Magnética , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos de Estresse Pós-Traumáticos/patologia , Atrofia , Encéfalo/metabolismo , Estudos de Casos e Controles , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
10.
J Endotoxin Res ; 7(4): 287-91, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11717583

RESUMO

The innate immune system coordinates the inflammatory response to pathogens. To do so, cells of the innate immune system must rapidly discriminate between self and non-self. All bacteria express membrane-associated lipoproteins. These molecules activate cells of the innate immune system to initiate host defense mechanisms. However, it is currently unknown how the innate immune system recognizes bacterial lipoproteins. Here, we describe that in response to bacterial lipoprotein, human Toll-like receptor-2 activates three different cellular responses: nuclear factor-kappaB dependent transcription, programmed cell death and reactive oxygen species production. We propose that Toll-like receptor-2 fulfils multiple roles in the genesis of the immune response to bacterial pathogens.


Assuntos
Apoptose/fisiologia , Proteínas de Drosophila , Glicoproteínas de Membrana/fisiologia , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Superfície Celular/fisiologia , Transdução de Sinais/fisiologia , Anticorpos Bloqueadores/farmacologia , Anticorpos Monoclonais/farmacologia , Proteínas de Bactérias/farmacologia , Linhagem Celular , Humanos , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/farmacologia , Lipoproteínas/farmacologia , Glicoproteínas de Membrana/imunologia , NF-kappa B/biossíntese , Receptores de Superfície Celular/imunologia , Explosão Respiratória/imunologia , Receptor 2 Toll-Like , Receptores Toll-Like
11.
Psychosom Med ; 63(6): 874-80, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11719624

RESUMO

OBJECTIVE: First popularized as neurasthenia in the late 1800s by American George Beard, asthenia has been viewed by Russian psychologists and flight surgeons as a major problem that affects cosmonauts participating in long-duration space missions. However, there is some controversy about whether this syndrome exists in space; this controversy is attributable in part to the fact that it is not recognized in the current American psychiatric diagnostic system. METHODS: To address this issue empirically, we retrospectively examined the data from our 4 1/2-year, NASA-funded study of crew member and mission control interactions during the Shuttle/Mir space program. Three of the authors identified eight items of stage 1 asthenia from one of our measures, the Profile of Mood States (POMS). Scores on these items from 13 Russian and American crew members were compared with scores derived from the opinions of six Russian space experts. RESULTS: Crew members' scores in space were significantly lower than the experts' scores on seven of the eight items, and they generally were in the "not at all" to "a little" range of the item scales. There were no differences in mean scores before and after launch or across the four quarters of the missions. There were no differences in response between Russian and American crew members. CONCLUSIONS: We could not demonstrate the presence of asthenia in space as operationally defined using the POMS. However, the POMS addresses only emotional and not physiological aspects of the syndrome, and the subject responses in our study generally were skewed toward the positive end of the scales. Further research on this syndrome needs to be done and should include physiological measures and measures that are specific to asthenia.


Assuntos
Astenia/diagnóstico , Voo Espacial , Adulto , Comparação Transcultural , Erros de Diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/diagnóstico , Estudos Retrospectivos , Federação Russa , Índice de Gravidade de Doença , Fatores de Tempo , Estados Unidos
12.
Acta Astronaut ; 49(3-10): 243-60, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11669114

RESUMO

BACKGROUND: Anecdotal reports from space and results from simulation studies on Earth have suggested that space crewmembers may experience decrements in their interpersonal environment over time and may displace tension and dysphoria to mission control personnel. METHODS: To evaluate these issues, we studied 5 American astronauts, 8 Russian cosmonauts, and 42 American and 16 Russian mission control personnel who participated in the Shuttle/Mir space program. Subjects completed questions from subscales of the Profile of Mood States, the Group Environment Scale, and the Work Environment Scale on a weekly basis before, during, and after the missions. RESULTS: Among the crewmembers, there was little evidence for significant time effects based on triphasic (U-shaped) or linear models for the 21 subscales tested, although the presence of an initial novelty effect that declined over time was found in three subscales for the astronauts. Compared with work groups on Earth, the crewmembers reported less dysphoria and perceived their crew environment as more constraining, cohesive, and guided by leadership. There was no change in ratings of mood and interpersonal environment before, during, and after the missions. CONCLUSIONS: There was little support for the presence of a moderate to strong time effect that influenced the space crews. Crewmembers perceived their work environment differently from people on Earth, and they demonstrated equanimity in mood and group perceptions, both in space and on the ground. Grant numbers: NAS9-19411.


Assuntos
Adaptação Psicológica , Astronautas/psicologia , Relações Interpessoais , Voo Espacial , Ausência de Peso , Medicina Aeroespacial , Afeto , Processos Grupais , Humanos , Modelos Psicológicos , Análise de Regressão , Federação Russa , Isolamento Social/psicologia , Inquéritos e Questionários , Estados Unidos
13.
J Physiol ; 536(Pt 2): 471-8, 2001 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11600682

RESUMO

1. Recombinant rat GABA(A) (alpha1beta2, alpha1beta2gamma2, beta2gamma2) and human GABA(C) (rho1) receptors were expressed in Xenopus oocytes to examine the effect of ultraviolet (UV) light on receptor function. 2. GABA-induced currents in individual oocytes expressing GABA receptors were tested by two-electrode voltage clamp before, and immediately after, 312 nm UV irradiation. 3. UV irradiation significantly potentiated 10 microM GABA-induced currents in alpha1beta2gamma2 GABA receptors. The modulation was irradiation dose dependent, with a maximum potentiation of more than 3-fold. 4. The potentiation was partially reversible and decayed exponentially with a time constant of 8.2 +/- 1.2 min toward a steady-state level which was still significantly elevated (2.7 +/- 0.3-fold) compared to the control level. 5. The effect of UV irradiation on GABA(A) receptors varied with receptor subunit composition. UV irradiation decreased the EC50 of the alpha1beta2, alpha1beta2gamma2 and beta2gamma2 GABA(A) receptors, but exhibited no significant effect on the rho1 GABA(C) receptor. 6. UV irradiation also significantly increased the maximum current 2-fold in alpha1beta2 GABA(A) receptors with little effect on the maximum of alpha1beta2gamma2 (1.1-fold) or beta2gamma2 (1.1-fold) GABA(A) receptors. 7. The effect of UV irradiation on GABA(A) receptors did not overlap the effect of the GABA receptor- allosteric modulator, diazepam. 8. The UV effect on GABA(A) receptors was not prevented by the treatment of the oocytes before and during UV irradiation with one of the following free-radical scavengers: 40 mM D-mannitol, 40 mM imidazole or 40 mM sodium azide. In addition, the effect was not mimicked by the free-radical generator, H2O2. 9. Potential significance and mechanism(s) of the UV effect on GABA receptors are discussed.


Assuntos
Receptores de GABA-A/química , Receptores de GABA-A/genética , Regulação Alostérica/efeitos da radiação , Animais , Diazepam/farmacologia , Relação Dose-Resposta à Radiação , Feminino , Sequestradores de Radicais Livres/farmacologia , Moduladores GABAérgicos/farmacologia , Expressão Gênica/fisiologia , Luz , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/efeitos da radiação , Oócitos/fisiologia , Técnicas de Patch-Clamp , Receptores de GABA/química , Receptores de GABA/genética , Retina/efeitos da radiação , Raios Ultravioleta , Xenopus laevis
14.
J Trauma Stress ; 14(3): 461-7, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11534878

RESUMO

This study assesses the efficacy of fluvoxamine treatment on different domains of subjective sleep quality in Vietnam combat veterans with chronic posttraumatic stress disorder (PTSD). Medically healthy male Vietnam theater combat veterans (N = 21) completed a 10-week open label trial. Fluvoxamine treatment led to improvements in PTSD symptoms and all domains of subjective sleep quality. The largest effect was for dreams linked to the traumatic experience in combat. In contrast, generic unpleasant dreams showed only a modest response to treatment. Sleep maintenance insomnia and the item "troubled sleep" showed a large treatment response, whereas sleep onset insomnia improved less substantially. These therapeutic benefits contrast with published reports that have found activating effects of Selective Serotonin Reuptake Inhibitors on the sleep electroencephalogram.


Assuntos
Fluvoxamina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Adulto , Idoso , Fluvoxamina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/epidemiologia , Escalas de Graduação Psiquiátrica , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Índice de Gravidade de Doença , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Resultado do Tratamento
15.
Infect Immun ; 69(10): 6248-55, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11553567

RESUMO

Shigella spp. cause dysentery, a severe form of bloody diarrhea. Apoptosis, or programmed cell death, is induced during Shigella infections and has been proposed to be a key event in the pathogenesis of dysentery. Here, we describe a novel cytotoxic activity in the sterile-culture supernatants of Shigella flexneri. An identical activity was identified in purified S. flexneri endotoxin, defined here as a mixture of lipopolysaccharide (LPS) and endotoxin-associated proteins (EP). Separation of endotoxin into EP and LPS revealed the activity to partition exclusively to the EP fraction. Biochemical characterization of S. flexneri EP and culture supernatants, including enzymatic deactivation, reverse-phase high-pressure liquid chromatography analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a Toll-like receptor-2 (TLR2) activation assay, indicates that the cytotoxic component is a mixture of bacterial lipoproteins (BLP). We show that biologically active BLP are liberated into culture supernatants of actively growing S. flexneri. In addition, our data indicate that BLP, and not LPS, are the component of endotoxin of gram-negative organisms responsible for activating TLR2. The activation of apoptosis by BLP shed from S. flexneri is discussed as a novel aspect of the interaction of bacteria with the host.


Assuntos
Apoptose , Proteínas de Bactérias/metabolismo , Proteínas de Drosophila , Lipoproteínas/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores de Superfície Celular/metabolismo , Shigella flexneri/metabolismo , Proteínas de Bactérias/biossíntese , Linhagem Celular , Fracionamento Químico , Cromatografia Líquida de Alta Pressão/métodos , Meios de Cultura , Humanos , Metabolismo dos Lipídeos , Lipopolissacarídeos/farmacologia , Lipoproteínas/biossíntese , Fenol/farmacologia , Toxina Shiga/farmacologia , Shigella flexneri/crescimento & desenvolvimento , Transdução de Sinais , Receptor 2 Toll-Like , Receptores Toll-Like , Ácido Tricloroacético/farmacologia
16.
Am J Psychiatry ; 158(9): 1480-5, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11532735

RESUMO

OBJECTIVE: Meeting criterion A2 for the diagnosis of posttraumatic stress disorder (PTSD) in DSM-IV requires that an individual have high levels of distress during or after the traumatic event. Because of the paucity of valid and reliable instruments for assessing such responses, the authors developed a 13-item self-report measure, the Peritraumatic Distress Inventory, to obtain a quantitative measure of the level of distress experienced during and immediately after a traumatic event. METHOD: The cross-sectional study group comprised 702 police officers and 301 matched nonpolice comparison subjects varying in ethnicity and gender who were exposed to a wide range of critical incidents. RESULTS: The Peritraumatic Distress Inventory was found to be internally consistent, with good test-retest reliability and good convergent and divergent validity. Even after controlling for peritraumatic dissociation and for general psychopathology, the authors found that Peritraumatic Distress Inventory scores correlated with two measures of posttraumatic stress symptoms. CONCLUSIONS: The Peritraumatic Distress Inventory holds promise as a measure of PTSD criterion A2. Future studies should prospectively examine the ability of the Peritraumatic Distress Inventory to predict PTSD and its associated biological and cognitive correlates in other trauma-exposed groups.


Assuntos
Inventário de Personalidade/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Adulto , Estudos Transversais , Transtornos Dissociativos/diagnóstico , Transtornos Dissociativos/epidemiologia , Transtornos Dissociativos/psicologia , Etnicidade/psicologia , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Polícia/estatística & dados numéricos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria , Reprodutibilidade dos Testes , Fatores Sexuais , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estados Unidos/epidemiologia
17.
J Nerv Ment Dis ; 189(7): 442-8, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11504321

RESUMO

We studied 655 urban police officers (21% female, 48% white, 24% black, and 28% Hispanic) to assess ethnic and gender differences in duty-related symptoms of posttraumatic stress disorder (PTSD). We obtained self-report measures of: a) PTSD symptoms, b) peritraumatic dissociation, c) exposure to duty-related critical incidents, d) general psychiatric symptoms, e) response bias due to social desirability, and f) demographic variables. We found that self-identified Hispanic-American officers evidenced greater PTSD symptoms than both self-identified European-American and self-identified African-American officers. These effects were small in size but they persisted even after controlling for differences in other relevant variables. Contrary to expectation, we found no gender differences in PTSD symptoms. Our findings are of note because: a) they replicate a previous finding of greater PTSD among Hispanic-American military personnel and b) they fail to replicate the well-established finding of greater PTSD symptoms among civilian women.


Assuntos
Etnicidade/estatística & dados numéricos , Polícia/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , California/epidemiologia , Comorbidade , Transtornos Dissociativos/diagnóstico , Transtornos Dissociativos/epidemiologia , Etnicidade/psicologia , Feminino , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Acontecimentos que Mudam a Vida , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Cidade de Nova Iorque/epidemiologia , Inventário de Personalidade/estatística & dados numéricos , Fatores Sexuais , Desejabilidade Social , Transtornos de Estresse Pós-Traumáticos/diagnóstico , População Urbana/estatística & dados numéricos
18.
J Physiol ; 535(Pt 1): 145-53, 2001 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-11507165

RESUMO

1. A recombinant adenovirus was generated with the human rho1 GABA(C) receptor subunit (adeno-rho). Patch-clamp and antibody staining were employed to confirm functional expression of recombinant rho1 receptors after infection of human embryonic kidney cells (HEK293 cell line), human embryonic retinal cells (911 cell line), dissociated rat hippocampal neurons and cultured rat hippocampal slices. 2. Standard whole-cell recording and Western blot analysis using rho1 GABA(C) receptor antibodies revealed that recombinant rho1 receptors were expressed in HEK293 and 911 cells after adeno-rho infection and exhibited properties similar to those of rho1 receptors after standard transfection. 3. Cultured rat hippocampal neurons (postnatal day (P)3-P5) did not show a native GABA(C)-like current. After adeno-rho infection, however, a GABA(C)-like current appeared in 70-90 % of the neurons. 4. Five days after infection, expression of GABA(C) receptors in hippocampal neurons significantly decreased native GABA(A) receptor currents from 1200 +/- 300 to 150 +/- 70 pA (n = 10). The native glutamate-activated current was unchanged. 5. Hippocampal slices (P8) did not show a native GABA(C)-like current, although recombinant rho1 receptors could be expressed in cultured hippocampal slices after adeno-rho infection. 6. These data indicate that an adenovirus can be used to express recombinant GABA(C) receptors in hippocampal neurons. This finding could represent an important step towards the gene therapy of CNS receptor-related diseases.


Assuntos
Adenoviridae/genética , Técnicas de Transferência de Genes , Vetores Genéticos , Hipocampo/metabolismo , Neurônios/metabolismo , Receptores de GABA-B/metabolismo , Receptores de GABA/fisiologia , Animais , Linhagem Celular , Condutividade Elétrica , Hipocampo/citologia , Humanos , Técnicas In Vitro , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de GABA/genética , Receptores de GABA/metabolismo , Receptores de GABA-B/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Fatores de Tempo
19.
Aviat Space Environ Med ; 72(5): 453-61, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11346012

RESUMO

BACKGROUND: Anecdotal reports from space and results from simulation studies on Earth have suggested that space crewmembers may experience decrements in their mood and interpersonal environment during the 2nd half of the mission and that negative emotions may be displaced to outside monitoring personnel. METHODS: To evaluate these issues, we studied 5 American astronauts, 8 Russian cosmonauts, and 42 American and 16 Russian mission control personnel who participated in the Shuttle/Mir space program. Subjects completed questions from the Profile of Mood States, the Group Environment Scale (GES), and the Work Environment Scale (WES) on a weekly basis during the missions. Subscale scores from these measures were analyzed using a piecewise linear regression approach that analyzed normally distributed subscales using a mixed model and non-normally distributed subscales by dichotomizing the variables and using a generalized estimating equation. RESULTS: After protecting against possible Type I errors due to multiple significance tests, only weak support was found for the biphasic model: the only significant findings in favor of the hypothesized 2nd half decrements in the interpersonal environment were in crewmember GES Leader Support and astronaut WES Work Pressure. Strongly consistent confirmation was found on all six tested measures for the hypothesized displacement of tension and dysphoria from crewmembers to mission control personnel. The hypothesized displacement of tension and dysphoria from mission control personnel to management was found on five of the six tested measures. CONCLUSIONS: The absence of moderate to strong support for the biphasic model suggests that crewmember interpersonal functioning does not depend appreciably on 1st half/2nd half time effects. The consistent support found for the displacement of tension and dysphoria suggests that countermeasures need to be developed to deal with this phenomenon in both crewmembers and mission control personnel.


Assuntos
Astronautas/psicologia , Deslocamento Psicológico , Relações Interprofissionais , Voo Espacial , Humanos , Modelos Lineares , Inquéritos e Questionários , Fatores de Tempo
20.
Clin Orthop Relat Res ; (384): 82-100, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11249183

RESUMO

The author describes application of intraoperative neurophysiologic monitoring to surgical treatment of lumbar stenosis. Benefits of somatosensory and motor evoked potential studies during surgical correction of spinal deformity are well known and documented. Free-running and evoked electromyographic studies during pedicle screw implantation is an accepted practice at many institutions. However, the functional integrity of spinal cord, cauda equina, and nerve roots should be monitored throughout every stage of surgery including exposure and decompression. Somatosensory evoked potentials monitor overall spinal cord function. Intraoperative electromyography provides continuous assessment of motor root function in response to direct and indirect surgical manipulation. Electromyographic activities observed during exposure and decompression of the lumbosacral spine included complex patterns of bursting and neurotonic discharge. In addition, electromyographic activities at distal musculature were elicited by impacting a surgical instrument or graft plug against bony elements of the spine. All electromyographic events provided direct feedback to the surgical team and were regarded as a cause for concern. Simultaneously monitored evoked potential and electromyographic studies protect spinal cord and nerve roots during seemingly low-risk phases of a surgical procedure when neurologic injury may occur and the patient is placed at risk for postoperative myelopathy or radiculopathy.


Assuntos
Vértebras Lombares/cirurgia , Monitorização Intraoperatória , Medula Espinal/fisiologia , Raízes Nervosas Espinhais/fisiologia , Estenose Espinal/cirurgia , Descompressão Cirúrgica , Eletromiografia/métodos , Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Humanos , Monitorização Intraoperatória/métodos
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