Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 77
Filtrar
1.
Ir Med J ; 115(2): 546, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35420007

RESUMO

Presentation A 24-year-old newly graduated junior doctor presented to the emergency department with acute onset chest pain, haemoptysis and exertional dyspnoea following a dry needling session. Diagnosis Chest x-ray showed bilateral pneumothoraces, worse on the right side. Treatment The bilateral pneumothoraces were treated conservatively with supplemental oxygen initially. On the second day of admission, repeat chest x-ray demonstrated a worsening right sided pneumothorax. While vitally stable, the patient however had become increasingly dyspnoeic, and a needle aspiration was performed on the right side with good effect. Conclusion The anatomical location targeted along with the patients low-normal BMI makes her high-risk when considering the skin-to-pleura distance. Although the incidence of pneumothorax is low, it is imperative that we improve awareness both for the treating physician and the diagnosing clinician. We must begin to fill the distinct lack in available literature surrounding the potential adverse effects of dry needling.


Assuntos
Terapia por Acupuntura , Agulhamento Seco , Pneumotórax , Terapia por Acupuntura/efeitos adversos , Adulto , Dor no Peito/etiologia , Dispneia/etiologia , Dispneia/terapia , Feminino , Humanos , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/terapia , Adulto Jovem
2.
BJOG ; 127(12): 1548-1556, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32633022

RESUMO

OBJECTIVE: To describe differences in outcomes between pregnant women with and without coronavirus dsease 2019 (COVID-19). DESIGN: Prospective cohort study of pregnant women consecutively admitted for delivery, and universally tested via nasopharyngeal (NP) swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcription-polymerase chain reaction. All infants of mothers with COVID-19 underwent SARS-CoV-2 testing. SETTING: Three New York City hospitals. POPULATION: Pregnant women >20 weeks of gestation admitted for delivery. METHODS: Data were stratified by SARS-CoV-2 result and symptomatic status, and were summarised using parametric and nonparametric tests. MAIN OUTCOME MEASURES: Prevalence and outcomes of maternal COVID-19, obstetric outcomes, neonatal SARS-CoV-2, placental pathology. RESULTS: Of 675 women admitted for delivery, 10.4% were positive for SARS-CoV-2, of whom 78.6% were asymptomatic. We observed differences in sociodemographics and comorbidities among women with symptomatic COVID-10 versus asymptomatic COVID-19 versus no COVID-19. Caesarean delivery rates were 46.7% in symptomatic COVID-19, 45.5% in asymptomatic COVID-19 and 30.9% in women without COVID-19 (P = 0.044). Postpartum complications (fever, hypoxia, readmission) occurred in 12.9% of women with COVID-19 versus 4.5% of women without COVID-19 (P < 0.001). No woman required mechanical ventilation, and no maternal deaths occurred. Among 71 infants tested, none were positive for SARS-CoV-2. Placental pathology demonstrated increased frequency of fetal vascular malperfusion, indicative of thrombi in fetal vessels, in women with COVID-19 versus women without COVID-19 (48.3% versus 11.3%, P < 0.001). CONCLUSION: Among pregnant women with COVID-19 at delivery, we observed increased caesarean delivery rates and increased frequency of maternal complications in the postpartum period. Additionally, intraplacental thrombi may have maternal and fetal implications for COVID-19 remote from delivery. TWEETABLE ABSTRACT: COVID-19 at delivery: more caesarean deliveries, postpartum complications and intraplacental thrombi.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , COVID-19 , Teste para COVID-19 , Estudos de Casos e Controles , Cesárea , Estudos de Coortes , Infecções por Coronavirus/complicações , Feminino , Hospitalização , Humanos , Recém-Nascido , Masculino , Cidade de Nova Iorque , Pandemias , Pneumonia Viral/complicações , Gravidez , SARS-CoV-2
4.
Contemp Clin Trials Commun ; 40: 101314, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38994348

RESUMO

Background: Posttraumatic Stress Disorder (PTSD) impacts both individual and relational functioning. Veteran couples are at increased risk of relationship distress due to military stressors such as deployment, family reintegration, and traumatic stress. Although both Cognitive-Behavioral Conjoint Therapy (CBCT) and its brief version (bCBCT) consistently have large effects on reducing PTSD symptoms, these treatments have more variable effects on relational outcomes. Given the impact of relationship functioning on the overall health of veterans, improving the effect of PTSD treatments on relationship functioning is an essential area of research. One promising path is the role of MDMA (3,4-methylenedioxymethamphetamine)-assisted therapy in augmenting the relational impact of established therapeutic interventions such as bCBCT. Method/Design: This is a single site, open-label study assessing the preliminary efficacy, safety, and acceptability of MDMA-assisted therapy in combination with bCBCT in 8 veterans with PTSD and their intimate partners (N = 16). Therapy teams trained in bCBCT and MDMA-assisted therapy will deliver bCBCT combined with two MDMA sessions and two couple emotion focused integration sessions. PTSD symptom severity and relationship functioning outcomes will be evaluated. Conclusion: This is the first study to examine the efficacy of MDMA-assisted bCBCT for improving PTSD and relationship functioning among a sample of U.S. military veterans and their partners. This project could provide an opportunity to pilot a scalable model of treating PTSD within the Veterans Affairs healthcare system and leverage the benefits of MDMA for veterans with PTSD, as well as the downstream benefits to their partner on both individual and relationship functioning. ClinicalTrials.gov Identifier: NCT05979844.

5.
Br J Cancer ; 109(8): 2131-41, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24052043

RESUMO

BACKGROUND: Taxanes are routinely used for the treatment of prostate cancer, however the majority of patients eventually develop resistance. We investigated the potential efficacy of EL102, a novel toluidine sulphonamide, in pre-clinical models of prostate cancer. METHODS: The effect of EL102 and/or docetaxel on PC-3, DU145, 22Rv1 and CWR22 prostate cancer cells was assessed using cell viability, cell cycle analysis and PARP cleavage assays. Tubulin polymerisation and immunofluorescence assays were used to assess tubulin dynamics. CWR22 xenograft murine model was used to assess effects on tumour proliferation. Multidrug-resistant lung cancer DLKPA was used to assess EL102 in a MDR1-mediated drug resistance background. RESULTS: EL102 has in vitro activity against prostate cancer, characterised by accumulation in G2/M, induction of apoptosis, inhibition of Hif1α, and inhibition of tubulin polymerisation and decreased microtubule stability. In vivo, a combination of EL102 and docetaxel exhibits superior tumour inhibition. The DLKP cell line and multidrug-resistant DLKPA variant (which exhibits 205 to 691-fold greater resistance to docetaxel, paclitaxel, vincristine and doxorubicin) are equally sensitive to EL102. CONCLUSION: EL102 shows potential as both a single agent and within combination regimens for the treatment of prostate cancer, particularly in the chemoresistance setting.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Sulfonamidas/farmacologia , Toluidinas/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Docetaxel , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Humanos , Masculino , Camundongos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Distribuição Aleatória , Sulfonamidas/administração & dosagem , Taxoides/administração & dosagem , Toluidinas/administração & dosagem , Tubulina (Proteína)/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Clin Exp Allergy ; 42(7): 1028-39, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22702502

RESUMO

BACKGROUND: Acid-sensing ion channels (ASIC) are a family of acid-activated ligand-gated cation channels. As tissue acidosis is a feature of inflammatory conditions, such as allergic rhinitis (AR), we investigated the expression and function of these channels in AR. OBJECTIVES: The aim of the study was to assess expression and function of ASIC channels in the nasal mucosa of control and AR subjects. METHODS: Immunohistochemical localization of ASIC receptors and functional responses to lactic acid application were investigated. In vitro studies on cultured epithelial cells were performed to assess underlying mechanisms of ASIC function. RESULTS: Lactic acid at pH 7.03 induced a significant rise in nasal fluid secretion that was inhibited by pre-treatment with the ASIC inhibitor amiloride in AR subjects (n = 19). Quantitative PCR on cDNA isolated from nasal biopsies from control and AR subjects demonstrated that ASIC-1 was equally expressed in both populations, but ASIC-3 was significantly more highly expressed in AR (P < 0.02). Immunohistochemistry confirmed significantly higher ASIC-3 protein expression on nasal epithelial cells in AR patients than controls (P < 0.01). Immunoreactivity for EPO+ eosinophils in both nasal epithelium and submucosa was more prominent in AR compared with controls. A mechanism of induction of ASIC-3 expression relevant to AR was suggested by the finding that eosinophil peroxidase (EPO), acting via ERK1/2, induced the expression of ASIC-3 in epithelial cells. Furthermore, using a quantitative functional measure of epithelial cell secretory function in vitro, EPO increased the air-surface liquid depth via an ASIC-dependent chloride secretory pathway. CONCLUSIONS: This data suggests a possible mechanism for the observed association of eosinophils and rhinorrhoea in AR and is manifested through enhanced ASIC-3 expression.


Assuntos
Peroxidase de Eosinófilo/metabolismo , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Sistema de Sinalização das MAP Quinases , Mucosa Nasal/metabolismo , Rinite Alérgica Sazonal/metabolismo , Canais de Sódio/biossíntese , Canais Iônicos Sensíveis a Ácido , Adolescente , Adulto , Biópsia , Células Cultivadas , Células Epiteliais/patologia , Feminino , Humanos , Ácido Láctico/farmacologia , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mucosa Nasal/patologia , Reação em Cadeia da Polimerase , Rinite Alérgica Sazonal/patologia
7.
Anticancer Res ; 27(3A): 1309-17, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17593624

RESUMO

BACKGROUND: Selection of the human drug sensitive and invasive cell line (MDA-MB-435S-F) with the chemotherapeutic agent paclitaxel, resulted in the development of drug resistant cell lines displaying enhanced invasion-related characteristics. MATERIALS AND METHODS: Serum-free conditioned media from the human cancer drug-sensitive and invasive cell line (MDA-MB-435S-F) and its paclitaxel-resistant superinvasive variant (MDA-MB-435S-F/Taxol10p4pSI) were analyzed using Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). RESULTS: A differentially expressed protein was observed at 7.6 kDa, which was 4-fold up-regulated in MDA-MB-435S-F/Taxol10p4pSI. The differentially expressed protein was identified using matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS), as a fragment of bovine transferrin. The transferrin receptor was also found to be overexpressed in the superinvasive cell line. CONCLUSION: Cleavage of serum proteins such as transferrin could provide a valuable source of markers for malignant tumours and could also play a role in aspects of cancer pathogenesis, such as tumour cachexia.


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Neoplasias da Mama/química , Proteínas de Neoplasias/isolamento & purificação , Fragmentos de Peptídeos/isolamento & purificação , Transferrina/isolamento & purificação , Adulto , Biomarcadores Tumorais/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Meios de Cultivo Condicionados , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Invasividade Neoplásica , Proteínas de Neoplasias/química , Paclitaxel/farmacologia , Fragmentos de Peptídeos/química , Receptores da Transferrina/biossíntese , Receptores da Transferrina/química , Receptores da Transferrina/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Transferrina/química
8.
Sci Rep ; 7(1): 13788, 2017 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-29062098

RESUMO

Cu(In,Ga)Se2 (CIGS) is presently the most efficient thin-film photovoltaic technology with efficiencies exceeding 22%. An important factor impacting the efficiency is metastability, where material changes occur over timescales of up to weeks during light exposure. A previously proposed (V Se -V Cu ) divacancy model presents a widely accepted explanation. We present experimental evidence for the optically induced metastability transition and expand the divacancy model with first-principles calculations. Using photoluminescence excitation spectroscopy, we identify a sub-bandgap optical transition that severely deteriorates the carrier lifetime. This is in accordance with the expanded divacancy model, which predicts that states below the conduction band are responsible for the metastability change. We determine the density-capture cross-section product of the induced lifetime-limiting states and evaluate their impact on device performance. The experimental and theoretical findings presented can allow assessment of metastability characteristics of leading thin-film photovoltaic technologies.

9.
Psychoneuroendocrinology ; 82: 164-172, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28550793

RESUMO

Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known. In this study, we examined the acute effects of LEU on fear extinction, hypothesizing that increased T levels following a single administration of LEU will facilitate extinction recall by altering neuronal activity within the fear extinction circuitry. Two groups of naïve adult male rats underwent a 3-day fear conditioning, extinction, and recall experiment. The delayed group (n=15) received a single injection of vehicle or LEU (1.2mg/kg) 3weeks before behavioral testing. The acute group (n=25) received an injection one day after fear conditioning, 30min prior to extinction training. Following recall, the brains for all animals were collected for c-fos immunohistochemistry. Blood samples were also collected and assayed for T levels. Acute administration of LEU increased serum T levels during extinction training and enhanced extinction recall 24h later. This enhanced extinction memory was correlated with increased c-fos activity within the infralimbic cortex and amygdala, which was not observed in the delayed group. These results suggest that the elevation in T induced by acute administration of LEU can influence extinction memory consolidation, perhaps through modification of neuronal activity within the infralimbic cortex and amygdala. This may be an important consideration in clinical applications of LEU and its effects on anxiety and cognition.


Assuntos
Extinção Psicológica/efeitos dos fármacos , Leuprolida/farmacologia , Memória/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Condicionamento Clássico/fisiologia , Condicionamento Psicológico/efeitos dos fármacos , Extinção Psicológica/fisiologia , Medo/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Sistema Hipotálamo-Hipofisário , Leuprolida/metabolismo , Masculino , Memória/fisiologia , Neurônios/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores LHRH/agonistas , Receptores LHRH/uso terapêutico , Testosterona/sangue
10.
Arch Intern Med ; 159(13): 1485-91, 1999 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-10399901

RESUMO

BACKGROUND: To determine whether human T-lymphotropic virus type II (HTLV-II) infection is associated with an increased incidence of bacterial infections, we prospectively observed cohorts of HTLV-I- and HTLV-II-infected and seronegative subjects in 5 US cities. METHODS: Of 1340 present and former blood donors examined at enrollment, 1213 (90.5%) were re-examined after approximately 2 years, including 136 HTLV-I- and 337 HTLV-II-seropositive subjects and 740 demographically stratified HTLV-seronegative subjects. All subjects were seronegative for human immunodeficiency virus. Odds ratios (ORs) for incident disease outcomes were adjusted for covariates, including age, sex, race or ethnicity, education, and, if significantly associated with the outcome, blood center, donation type, income, smoking, alcohol intake, and injected drug use. RESULTS: Compared with seronegative status, HTLV-II infection was associated with an increased incidence of bronchitis (OR, 1.81; 95% confidence interval [CI], 1.20-2.75), bladder and/or kidney infection (OR, 1.94; 95% CI, 1.26-2.98), oral herpes infection (OR, 9.54; 95% CI, 3.33-27.32), and a borderline increased incidence of pneumonia (OR, 2.09; 95% CI, 0.92-4.76); HTLV-I infection was associated with an increased incidence of bladder and/or kidney infection (OR, 2.79; 95% CI, 1.63-4.79). One incident case of HTLV-I-positive adult T-cell leukemia was observed (incidence, 348 per 100,000 HTLV-I person-years), and 1 case of HTLV-II-positive tropical spastic paraparesis-HTLV-associated myelopathy was diagnosed (incidence, 140 per 100,000 HTLV-II person-years). CONCLUSIONS: These data support an increased incidence of infectious diseases among otherwise healthy HTLV-II- and HTLV-I-infected subjects. They are also consistent with the lymphoproliferative effects of HTLV-I, and with neuropathic effects of HTLV-I and HTLV-II.


Assuntos
Doenças Transmissíveis/complicações , Doenças Transmissíveis/epidemiologia , Infecções por HTLV-I/complicações , Infecções por HTLV-II/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Feminino , Seguimentos , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/etiologia , Infecções por HTLV-II/etiologia , Humanos , Incidência , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
11.
Rev Sci Instrum ; 86(1): 013907, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25638097

RESUMO

Fiber-fed time-resolved photoluminescence is demonstrated as a tool for immediate process feedback after deposition of the absorber layer for CuInxGa(1-x)Se2 and Cu2ZnSnSe4 photovoltaic devices. The technique uses a simplified configuration compared to typical laboratory time-resolved photoluminescence in the delivery of the exciting beam, signal collection, and electronic components. Correlation of instrument output with completed device efficiency is demonstrated over a large sample set. The extraction of the instrument figure of merit, depending on both the initial luminescence intensity and its time decay, is explained and justified. Limitations in the prediction of device efficiency by this method, including surface effect, are demonstrated and discussed.

12.
Am J Psychiatry ; 148(3): 374-5, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1992843

RESUMO

The authors used a double-blind crossover design to observe the effect of transdermally administered nicotine on the smoking behavior of 13 psychiatric patients who were not trying to stop smoking. The patients smoked significantly fewer cigarettes while receiving nicotine than while receiving placebo. These data suggest that transdermally administered nicotine can be a useful adjunct in treating nicotine-addicted psychiatric patients in a non-smoking environment.


Assuntos
Transtornos Mentais/psicologia , Nicotina/administração & dosagem , Prevenção do Hábito de Fumar , Administração Cutânea , Adulto , Método Duplo-Cego , Humanos , Transtornos Mentais/complicações , Pessoa de Meia-Idade , Nicotina/efeitos adversos , Placebos , Fumar/psicologia , Síndrome de Abstinência a Substâncias/prevenção & controle , Tabagismo/prevenção & controle , Tabagismo/psicologia
13.
Cancer Epidemiol Biomarkers Prev ; 5(7): 487-94, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8827351

RESUMO

Evidence is accumulating that folate, a B vitamin found in green leafy vegetables, may affect the development of neoplasia. We examined the relationship between folate status and colorectal cancer in a case-control study nested within the Alpha-Tocopherol Beta-Carotene Study cohort of male smokers 50-69 years old. Serum folate was measured in 144 incident cases (91 colon, 53 rectum) and 276 controls matched to cases on baseline age, clinic, and time of blood collection. Baseline dietary folate was available from a food-use questionnaire for 386 of these men (92%). Conditional logistic regression modeling was used. No statistically significant association was observed between serum folate and colon or rectal cancer. Although a 2-fold increase in rectal cancer risk was suggested for men with serum folate > 2.9 ng/ml and those in the highest quartile of energy-adjusted folate intake, there was no evidence of a monotonic dose-response, and all confidence intervals included unity. For dietary folate and colon cancer, odds ratios of 0.40 [95% confidence interval (CI), 0.16-0.96], 0.34 (95% CI, 0.13-0.88), and 0.51 (95% CI, 0.20-1.31) were obtained for the second through fourth quartiles of energy-adjusted folate intake, respectively, compared to the first (P for trend = 0.15). Furthermore, men with a high-alcohol, low-folate, low-protein diet were at higher risk for colon cancer than men who consumed a low-alcohol, high-folate, high-protein diet (OR, 4.79; 95% CI, 1.36-16.93). This study suggests a possible association between low folate intake and increased risk of colon cancer (but not rectal cancer) and highlights the need for further studies that measure dietary folate and methionine, along with biochemical measures of folate (i.e., erythrocyte and serum), homocysteine, and vitamin B12.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais , Ácido Fólico/sangue , Fumar , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/fisiopatologia , Intervalos de Confiança , Finlândia/epidemiologia , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sensibilidade e Especificidade
14.
J Med Chem ; 44(15): 2421-31, 2001 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-11448224

RESUMO

p56lck is a member of the src family of tyrosine kinases and plays a critical role in the signal transduction events that lead to T cell activation. Ligands for the p56lck SH2 domain have the potential to disrupt the interaction of p56lck with its substrates and derail the signaling cascade that leads to the production of cytokines such as interleukin-2. Starting from the quintuply charged (at physiological pH) phosphorylated tetrapeptide, AcpYEEI, we recently disclosed (J. Med. Chem. 1999, 42, 722 and J. Med. Chem. 1999, 42, 1757) the design of the modified dipeptide 3, which carries just two charges at physiological pH. Here we present the elaboration of 3 to the nonpeptidic, monocharged compound, 9S. This molecule displays good binding affinity for the p56lck SH2 domain (K(d) 1 microM) and good cell permeation, and this combination of properties allowed us to demonstrate clear-cut inhibitory effects on a very early event in T cell activation, namely calcium mobilization.


Assuntos
Permeabilidade da Membrana Celular , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Fenilalanina/síntese química , Piridonas/síntese química , Domínios de Homologia de src , Células CACO-2 , Cálcio/metabolismo , Humanos , Células Jurkat , Ligantes , Modelos Moleculares , Fenilalanina/análogos & derivados , Fenilalanina/química , Fenilalanina/farmacologia , Piridonas/química , Piridonas/farmacologia
15.
Biotechniques ; 6(5): 460-9, 1988 May.
Artigo em Inglês | MEDLINE | ID: mdl-3273407

RESUMO

Procedures are presented for reliable and accurate nucleotide sequence analysis using as template supercoiled DNA prepared by a modified rapid boiling minipreparation protocol. This method yields DNA templates suitable for sequencing within 1 h of bacterial harvest. We describe optimal reaction conditions for supercoiled miniprep DNA sequencing using a modified T7 DNA polymerase (Sequenase) in dideoxynucleotide chain termination reactions. We demonstrate that under these conditions, the sequencing data obtained with miniprep DNA is indistinguishable from that obtained with CsCl purified supercoiled DNA or from that obtained using single stranded DNA templates. We further show that the supercoiled DNA sequencing reactions can be analyzed on a commercially available automated DNA sequencing system that detects 32P labeled DNA during its electrophoretic separation. Taken together, these developments represent a significant improvement in the process of nucleotide sequence analysis.


Assuntos
DNA Super-Helicoidal/análise , DNA Polimerase Dirigida por DNA , Fagos T/genética , Eletroforese em Gel de Poliacrilamida
16.
Biotechniques ; 7(8): 866-77, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2698663

RESUMO

We describe a system for the real-time detection of radioactively labeled DNA molecules in gel matrix, and we demonstrate the application of this system to DNA sequence analysis. DNA sequencing reactions prepared by the Sanger chain termination method are resolved by electrophoresis on 8% polyacrylamide gels. During electrophoresis the 32P-labeled DNA fragments are detected by solid state detectors positioned 22 cm from the top surface of the gel. This system is able to resolve a DNA sequence of 300 bases or greater. Optimized protocols that allow sequence information to be obtained from single stranded and double-stranded templates are described. A linear relationship exists between the input dpm and the integrated peak values over a 20-fold range indicating that accurate DNA quantitation is also possible using this system.


Assuntos
DNA/análise , Técnicas Genéticas/instrumentação , Automação , Sequência de Bases , Partículas beta , DNA/genética , DNA de Cadeia Simples , DNA Super-Helicoidal , Interpretação Estatística de Dados , Eletroforese em Gel de Poliacrilamida , Desenho de Equipamento , Dados de Sequência Molecular , Radioisótopos de Fósforo , Moldes Genéticos
17.
Leuk Res ; 7(4): 557-63, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6578395

RESUMO

Cells from the spleens of Brown Norway rats made leukemic with the in vivo-passaged promyelocytic line BNML have been adapted to in vitro culture in RPMI-1640 medium supplemented with 4% rat serum and 6% fetal bovine serum. The presence of rat serum, which also was associated with suppression of fibroblasts, appeared to be required for initial growth. In contrast to the parent this new cell line (BNML-RS) was predominantly myeloblastic under standard conditions of culture with only 4-10% of cells showing granules or stainable peroxidase. However, when passaged through an animal, 60-70% contained both granules and peroxidase. Neither parent nor established line evolved to the polymorph stage when assessed for terminal maturation after exposure to dimethyl sulfoxide or retinoic acid. These cells now extend the limited number of myeloid lines available and potentially are a useful model in which to study the controlling events in early myeloblast maturation.


Assuntos
Leucemia Mieloide Aguda/patologia , Animais , Divisão Celular , Linhagem Celular , Células Cultivadas , Ratos
18.
Leuk Res ; 8(1): 81-6, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6583463

RESUMO

The characteristics of tumor cells that enable invasion into normal tissues are not well understood. We have derived variants of the promyelocytic leukemia of the Brown Norway rat (BNML) that exhibit a high incidence of growth in the epidural space and produce paralysis of the hind limbs. This unique animal model mimics a major cause of morbidity in human cancer and provides a reproducible system in which to study the determinants of metastasis localization.


Assuntos
Leucemia Mieloide Aguda/patologia , Neoplasias da Coluna Vertebral/secundário , Animais , Espaço Epidural , Metástase Neoplásica , Ratos , Ratos Endogâmicos BN
19.
J Psychiatr Res ; 28(3): 289-301, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7932288

RESUMO

The purpose of this research was to determine the relationship between schizophrenic individuals' cognitive functioning and their performance in interpersonal interactions and skills training procedures. Thirty schizophrenic individuals and 15 non-mentally ill individuals were administered two versions of the Continuous Performance Test, the Span of Apprehension Test, the Digit Span Distractibility Test, the Assessment of Interpersonal Problem Solving Skills, and three elemental skills training tasks. Vigilance level as measured by the Continuous Performance Test was substantially correlated with performance in both roleplayed interactions and skills training tasks, while recall memory as measured by the Digit Span Distractibility Test was correlated with performance in the skills training tasks independently of vigilance level. Thus, the results indicated that the cognitive dysfunctions of schizophrenia are associated with poorer social functioning and with reduced performance in the elemental procedures that constitute efforts to improve that functioning.


Assuntos
Atividades Cotidianas , Transtornos Cognitivos/diagnóstico , Relações Interpessoais , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adolescente , Adulto , Transtornos Cognitivos/reabilitação , Feminino , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Resolução de Problemas , Testes Psicológicos , Esquizofrenia/reabilitação
20.
J Am Acad Child Adolesc Psychiatry ; 38(8): 1016-23, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10434494

RESUMO

OBJECTIVE: To examine risk and protective processes for posttraumatic stress reactions and negative sequelae following the Northridge earthquake (EQ) among youths diagnosed for pre-EQ psychopathology. METHOD: Symptoms of posttraumatic stress disorder (PTSD), depression, general anxiety, and social impairment were evaluated using telephone interviews among 66 children participating in a family-genetic study of childhood-onset depression at the time of the EQ. RESULTS: Significant predictors of PTSD symptoms 1 year after the EQ included perceived stress and resource loss associated with the EQ, a pre-EQ anxiety disorder, and more frequent use of cognitive and avoidance coping strategies. PTSD symptoms were associated with high rates of concurrent general anxiety symptoms, depressive symptoms, and social adjustment problems with friends. The only significant correlation between sibling scores was on measures of sibling reports of objective exposure. CONCLUSIONS: Preexisting anxiety disorders represent a risk factor for postdisaster PTSD reactions. Postdisaster services need to attend to the needs of these youths as well as those of youths experiencing high levels of subjective stress, resource loss, and/or high exposure. That children within families show significant variation in postdisaster reactions underscores the need for attention to individual child characteristics and unshared environmental attributes.


Assuntos
Transtornos de Ansiedade/epidemiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Transtorno Depressivo/epidemiologia , Desastres , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adolescente , Análise de Variância , Transtornos de Ansiedade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Criança , Comorbidade , Transtorno Depressivo/psicologia , Feminino , Humanos , Modelos Lineares , Los Angeles/epidemiologia , Masculino , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologia
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa