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1.
J Health Commun ; 21(2): 257-65, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26735927

RESUMEN

Research suggests that communications about racial health disparities may adversely affect Blacks. In this study, we varied the message content (Black-White cardiovascular-related disparities + neutral health topics vs. neutral health topics only) embedded in public service announcements given to Black and White participants (N = 86) and had them complete a purported health self-assessment. We used the number of items completed as a measure of task persistence. Our results showed that participants in the disparities condition completed fewer items on average than participants in the neutral condition (p < .01). Planned contrasts revealed that this effect was driven by the responses of Blacks who completed fewer items in the disparities condition (p < .01), though Whites evinced a comparable condition-based trend (p = .12). We found no Black-White differences in the number of items completed in either of our experimental conditions (ps ≥ .53). Although preliminary, our findings suggest that Blacks and Whites exposed to comparative racial disparities messaging about cardiovascular diseases could experience reduced task persistence. Research implications and study limitations are also discussed.


Asunto(s)
Negro o Afroamericano/psicología , Comunicación en Salud/métodos , Disparidades en el Estado de Salud , Análisis y Desempeño de Tareas , Adolescente , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/etnología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Población Blanca/psicología , Población Blanca/estadística & datos numéricos , Adulto Joven
2.
Epilepsy Behav ; 48: 88-95, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26136184

RESUMEN

BACKGROUND: A primary brain tumor (PBT) is often a fatal disease of the nervous system and has a serious impact on health-related quality of life (HRQOL). Presence of epilepsy and adverse reactions from tumor and epilepsy treatments may cause additional decline in HRQOL. OBJECTIVES: We aimed to study the impact of epileptic seizures on cognition, mood, and HRQOL in patients with brain tumor-related epilepsy. MATERIALS AND METHOD: Patients were grouped on an ordinal scale according to epilepsy burden from none to severe based on the presence of epileptic seizures and seizure frequency: L1, no epilepsy; L2, with epilepsy, seizure-free in the last 6 months with antiepileptic drugs; and L3, with epilepsy, at least one seizure in the last 6 months with AEDs. Health-related quality of life was measured by Functional Assessment of Cancer Therapy-Brain (FACT-Br) and Quality of Life in Epilepsy-31 (QOLIE-31) tools, cognition by the Montreal Cognitive Assessment (MoCA) tool and Frontal Assessment Battery (FAB), mood by the Hospital Anxiety and Depression Scale (HADS), activities of daily living (ADLs) by the Barthel Index (BI), and performance status by the Karnofsky Performance Status (KPS) scale in patients with primary brain tumors at least one month following neurosurgery with or without radiotherapy and chemotherapy. RESULTS: Eighty-one patients with a diagnosis of primary brain tumors were recruited. Sixty-eight percent of patients were diagnosed with primary brain tumor-related epilepsy, 50.61% patients had cognitive impairment, 33% had abnormal scores in the anxiety scale, and 34% had abnormal scores in the depression scale. There were no statistically significant differences in these scores among L1, L2, and L3 groups. There were statistically significant differences in duration of disease and KPS and BI scores between L1 and L3 groups. The L3 group has significantly longer duration of disease and scored low in both the BI and KPS scale when compared to the L1 group. All patients with primary brain tumors scored significantly low in FACT-Br 'physical well-being' (PWB) and 'emotional well-being' (EWB) and high in 'social well-being' (SWB) when compared to healthy controls. When scores of each group were individually compared to healthy controls, the L3 group showed the lowest scores in PWB, EWB, and 'functional well-being'. In SWB, L1 and L2 groups showed statistically significantly high scores when compared to normative data. The QOLIE-31 applied to groups with epilepsy showed statistically significantly lower scores in the L3 group when compared to the L2 group in 'cognitive' and 'social functioning' domains. On multivariate analysis, both poor performance status and frequency of seizures were found to be independent risk factors for poor HRQOL when FACT-Br mean scores were compared. Level of seizures was found to be an independent risk factor for poor HRQOL when QOLIE-31 scores were compared between L2 and L3 groups. DISCUSSION: Presence of brain tumors could be attributed to cognitive impairment irrespective of the presence of epilepsy in our cohort. High seizure burden is an independent risk factor for poor HRQOL in patients with primary brain tumors. The QOLIE-31 is a more sensitive tool than the FACT-Br because of the presence of a seizure-related questionnaire.


Asunto(s)
Afecto , Anticonvulsivantes/uso terapéutico , Neoplasias Encefálicas/complicaciones , Trastornos del Conocimiento/etiología , Cognición/fisiología , Epilepsia/tratamiento farmacológico , Calidad de Vida/psicología , Actividades Cotidianas/psicología , Adulto , Anciano , Anciano de 80 o más Años , Anticonvulsivantes/efectos adversos , Ansiedad/psicología , Neoplasias Encefálicas/psicología , Neoplasias Encefálicas/cirugía , Trastornos del Conocimiento/diagnóstico , Epilepsia/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurocirugia , Escalas de Valoración Psiquiátrica , Convulsiones/tratamiento farmacológico , Convulsiones/psicología , Índice de Severidad de la Enfermedad , Ajuste Social , Encuestas y Cuestionarios
3.
Lupus ; 22(6): 639-43, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23651859

RESUMEN

We report a female with infantile onset of systemic lupus erythematosus secondary to C1q deficiency, in whom we identified a novel homozygous mutation in C1qB. The patient developed a progressive encephalopathy associated with spasticity, and suffered several arterial ischaemic strokes. Cerebral imaging demonstrated acquired intracranial calcification and a cerebral vasculopathy reminiscent of moyamoya. This case demonstrates overlap with some features of Aicardi-Goutières syndrome which, like C1q deficiency, is a monogenic cause of inflammation involving dysregulation of the innate immune system and stimulation of a type I interferon response.


Asunto(s)
Complemento C1q/deficiencia , Lupus Eritematoso Sistémico/etiología , Enfermedad de Moyamoya/fisiopatología , Adolescente , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/fisiopatología , Isquemia Encefálica/etiología , Isquemia Encefálica/patología , Calcinosis/etiología , Calcinosis/patología , Complemento C1q/genética , Femenino , Humanos , Lupus Eritematoso Sistémico/fisiopatología , Enfermedad de Moyamoya/etiología , Mutación , Malformaciones del Sistema Nervioso/diagnóstico , Malformaciones del Sistema Nervioso/fisiopatología
4.
Cureus ; 15(8): e43582, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37719562

RESUMEN

Pyomyositis is a skeletal muscle infection mainly found in tropical regions. It commonly affects larger muscles, especially those of the hips. MRI tends to be the gold standard for diagnosis. Staphylococcus aureus remains the predominant causal organism in most cases of pyomyositis. Immunocompromised patients are more likely to be susceptible to this infection. In our case, an immunocompetent 27-year-old male in rural southwest Virginia was found to have a large abscess in his upper arm. Contrast-enhanced CT scan was acquired prior to drainage, leading to the diagnosis of pyomyositis. Empiric treatment with IV vancomycin 1 g q 24 hours and piperacillin/tazobactam 3.375 mg q 8 hours, prompt incision and drainage, and negative pressure wound VAC led to a complete resolution of the infection.

5.
J Clin Neurosci ; 59: 265-269, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30314922

RESUMEN

INTRODUCTION: Seizures are an important cause of morbidity in patients with low grade gliomas with approximately 40% of cases drug resistant. The pathogenesis is quite complex and poorly understood. The treatment aims vary between almost purely epilepsy considerations and those that are primarily oncologic. AIM: To determine whether patients who present with seizures and are found to have a low grade glioma have better outcomes when managed through a specialized epilepsy unit compared to the general neurosurgical service. METHODS: A review of the prospectively collected database was performed over a 10 year period to identify 48 adult patients who present with a seizure and were subsequently found to have a low grade glioma. These patients were analysed with respect to management through the specialized epilepsy service or the general neurosurgical service. The primary outcome was Engel classification between the two groups. Secondary outcomes included recurrence, postoperative deficits, delay to surgery, histology, grade and extent of resection. OUTCOMES: The patients managed through the epilepsy service had significantly higher rate of favourable Engel outcomes (I and II) compared to the general neurosurgery service (OR: 13.2, 95% CI: 1.239-140.679; P = 0.033). The epilepsy surgery group patients had a significantly higher delay to surgery (P < 0.001). The patients in the epilepsy service had a significantly higher resection ratio compared to the general neurosurgery service (73% vs 127%, P = 0.014). Rates of recurrence were not different between the two groups. CONCLUSION: Patients with tumour related epilepsy who undergo an intensive presurgical evaluation may obtain better seizure related outcomes.


Asunto(s)
Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/cirugía , Epilepsia/etiología , Glioma/complicaciones , Glioma/cirugía , Adulto , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Procedimientos Neuroquirúrgicos/métodos , Estudios Retrospectivos , Resultado del Tratamiento
6.
J Dev Behav Pediatr ; 39(6): 508-515, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29782387

RESUMEN

OBJECTIVE: Informed by the family stress and family investment models, this study investigated whether income is indirectly related to adherence and glycemic control through parenting constructs among youth with type 1 diabetes (TID). METHODS: Youth and their families (n = 390) from 4 geographically dispersed pediatric endocrinology clinics in the United States were participants in a multisite clinical trial from 2006 to 2009 examining the efficacy of a clinic-integrated behavioral intervention targeting family disease management for youth with TID. Baseline data were collected from youth aged 9 to 14 years and their parents. Parents reported family income and completed a semistructured interview assessing diabetes management adherence. Parents and children reported diabetes-specific parent-child conflict. Children completed measures of collaborative parent involvement and authoritative parenting. Hemoglobin A1c (HbA1c), a biomarker of glycemic control, was analyzed centrally at a reference laboratory. The relations of income, parenting variables, regimen, adherence, and HbA1c were examined using structural equation modeling. RESULTS: Lower family income was associated with greater parent-child conflict and a less authoritative parenting style. Authoritative parenting was associated with more collaborative parent involvement and less parent-child conflict, both of which were associated with greater adherence, which was associated with more optimal glycemic control (p < 0.05 all associations). Indirect effects of family income on adherence and glycemic control through parenting constructs were significant (p < 0.001). CONCLUSION: Findings lend support for the family stress and family investment models, suggesting that lower family income may negatively impact parent-child constructs, with adverse effects on diabetes management.


Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Renta/estadística & datos numéricos , Relaciones Padres-Hijo , Responsabilidad Parental , Cooperación del Paciente/estadística & datos numéricos , Automanejo/estadística & datos numéricos , Adolescente , Niño , Diabetes Mellitus Tipo 1/sangre , Femenino , Hemoglobina Glucada , Humanos , Masculino
7.
J Clin Neurosci ; 50: 262-267, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29398196

RESUMEN

Monitoring optic nerve sheath meningiomas (ONSM) in Neurofibromatosis type 2 (NF2) patients remains difficult. Other ocular manifestations of NF2 may obscure ophthalmic assessment of optic nerve function in these patients. Serial magnetic resonance imaging (MRI) used to assess the optic nerve is not without limitations, being expensive and often requiring general anaesthetic in children, with associated risks. This study was undertaken to describe the use of multifocal visual evoked potentials (multifocal VEP, mfVEP) in the regular monitoring of NF2 patients with ONSM. This study involved three NF2 patients with ONSM who undertook mfVEP testing at an academic ophthalmic centre. Same day mfVEP and routine ophthalmic testing were undertaken. Topographical function of the optic nerve was assessed, utilising tools such as asymmetry deviation and accumap severity index. Results were assessed alongside MRI and visual acuity (VA). From the three patients, five eyes had ONSMs, of which two caused unilateral blindness. The remaining three affected eyes had initial VAs 6/6, 6/24, and 6/18. Over follow up, ranging from 5 to 12 years, all tumours progressed, and VA declined for all patients. Multifocal VEP detected optic nerve functional loss corresponding with visual decline. This case series suggests mfVEP is effective in the objective topographic monitoring of optic nerve function in NF2 patients with ONSM. Due also to its safety in a paediatric population, the test may be considered in the routine monitoring of these patients, to be used to assist regular ophthalmic review and MRI scans.


Asunto(s)
Potenciales Evocados Visuales , Neoplasias Meníngeas/patología , Meningioma/patología , Neurofibromatosis 2/complicaciones , Enfermedades del Nervio Óptico/diagnóstico , Trastornos de la Visión/diagnóstico , Adulto , Niño , Femenino , Humanos , Imagen por Resonancia Magnética/efectos adversos , Masculino , Neoplasias Meníngeas/complicaciones , Meningioma/complicaciones , Persona de Mediana Edad , Enfermedades del Nervio Óptico/etiología , Enfermedades del Nervio Óptico/patología , Trastornos de la Visión/etiología , Campos Visuales
8.
Mol Cell Biol ; 9(12): 5746-9, 1989 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2586530

RESUMEN

At least two separate but interdependent events are required to attain autonomous growth as a consequence of ectopic expression of the multilineage colony-stimulating factor gene in hematopoietic progenitor cells. The rate at which the second event occurs is more than 3 orders of magnitude higher in precursor cell lines (FDC-P1 or FDC-P2) than in stem cell lines (FDC-Pmix). Autonomous, but not density-dependent, growth is tightly coupled to tumorigenicity in precursor cells; however, neither growth-factor-independent nor autonomously growing stem cell lines are tumorigenic.


Asunto(s)
Transformación Celular Neoplásica , Factores Estimulantes de Colonias/genética , Expresión Génica , Células Madre Hematopoyéticas/citología , Mutación , Animales , División Celular/efectos de los fármacos , Línea Celular , Factores Estimulantes de Colonias/inmunología , Factores Estimulantes de Colonias/farmacología , Vectores Genéticos , Células Madre Hematopoyéticas/metabolismo , Sueros Inmunes , Cinética , Ratones
10.
J Stud Alcohol ; 67(4): 519-28, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16736071

RESUMEN

OBJECTIVE: Despite minimum-purchase-age laws, young people regularly drink alcohol. This study estimated the magnitude and costs of problems resulting from underage drinking by category-traffic crashes, violence, property crime, suicide, burns, drownings, fetal alcohol syndrome, high-risk sex, poisonings, psychoses, and dependency treatment-and compared those costs with associated alcohol sales. Previous studies did not break out costs of alcohol problems by age. METHOD: For each category of alcohol-related problems, we estimated fatal and nonfatal cases attributable to underage alcohol use. We multiplied alcohol-attributable cases by estimated costs per case to obtain total costs for each problem. RESULTS: Underage drinking accounted for at least 16% of alcohol sales in 2001. It led to 3,170 deaths and 2.6 million other harmful events. The estimated $61.9 billion bill (relative SE = 18.5%) included $5.4 billion in medical costs, $14.9 billion in work loss and other resource costs, and $41.6 billion in lost quality of life. Quality-of-life costs, which accounted for 67% of total costs, required challenging indirect measurement. Alcohol-attributable violence and traffic crashes dominated the costs. Leaving aside quality of life, the societal harm of $1 per drink consumed by an underage drinker exceeded the average purchase price of $0.90 or the associated $0.10 in tax revenues. CONCLUSIONS: Recent attention has focused on problems resulting from youth use of illicit drugs and tobacco. In light of the associated substantial injuries, deaths, and high costs to society, youth drinking behaviors merit the same kind of serious attention.


Asunto(s)
Consumo de Bebidas Alcohólicas/economía , Trastornos Relacionados con Alcohol/economía , Costo de Enfermedad , Costos de la Atención en Salud , Problemas Sociales/economía , Accidentes de Tránsito/economía , Accidentes de Tránsito/mortalidad , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/mortalidad , Trastornos Relacionados con Alcohol/epidemiología , Trastornos Relacionados con Alcohol/mortalidad , Encuestas Epidemiológicas , Humanos , Modelos Económicos , Años de Vida Ajustados por Calidad de Vida , Estados Unidos/epidemiología , Violencia/economía
11.
J Safety Res ; 37(4): 385-93, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17020771

RESUMEN

INTRODUCTION: Young unlicensed drivers' involvement in fatal crashes is a recurrent problem in the United States. METHODS: This descriptive study extracted cross-sectional data on fatal crashes from the Fatality Analysis Reporting System from 1998 to 2002. Young unlicensed driver fatal crashes are examined by age, gender, and region. RESULTS: There were 2,452 young unlicensed driver fatal crashes representing 10.8% of all young drivers' fatal crashes. By age, 72.5% are over 15 years, males are involved in 74.5%, and southern and western states have a higher percent of young unlicensed driver fatal crashes. CONCLUSIONS: Subgroups of young people based on their age, gender, and region are over-represented in fatal crashes as unlicensed drivers. Further studies are needed to investigate the context and factors of young unlicensed drivers, essential to tailor interventions. IMPACT ON INDUSTRY: Young unlicensed drivers circumvent the established licensing process and pose a serious threat to themselves and other road users.


Asunto(s)
Accidentes de Tránsito/mortalidad , Conducta del Adolescente , Conducta Infantil , Concesión de Licencias/estadística & datos numéricos , Vehículos a Motor/estadística & datos numéricos , Asunción de Riesgos , Accidentes de Tránsito/psicología , Adolescente , Factores de Edad , Examen de Aptitud para la Conducción de Vehículos , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Vehículos a Motor/legislación & jurisprudencia , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiología
12.
Physiol Behav ; 86(3): 407-14, 2005 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-16165169

RESUMEN

First-order kinetics is based on simple exponential decay, usually expressed in base e (Naperian) notation. "Nonexponential" processes, for example, S-shaped functions, are frequently modeled as sums of that elemental construct, and the number of rate constants increases with the number of such terms. A powerful descriptive alternative to sums of simple exponentials is the Gompertz function. In Gompertz kinetics, the rate coefficient of an exponential process is assumed to change exponentially with the independent variable. Nonexponential processes are easily modeled, more efficiently and more accurately than is possible with standard kinetics. Application of Gompertz kinetics to neuroscience research topics ranging from cognitive to molecular is presented to illustrate the power of the model: distribution of nerve fiber diameters, conditioning-testing responses of excitable nerve, psychophysical estimates of taste intensity magnitude, time course of synaptic current, and behavior of membrane conductance during voltage clamp of squid axon.


Asunto(s)
Cinética , Modelos Biológicos , Neurociencias , Animales , Interpretación Estadística de Datos , Humanos , Potenciales de la Membrana/fisiología , Neuronas/fisiología , Neurociencias/métodos
13.
Suicide Life Threat Behav ; 35(4): 425-35, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16184697

RESUMEN

Responses to the 1999 Youth Risk Behavior Survey including suicide ideation, attempt, medically treated attempt, and six problem behaviors were analysed. Youth across the spectrum ideated. Overwhelmingly, the 17% of youth with more than three problem behaviors were the youth who acted; they accounted for 60% of medically treated suicidal acts. Compared to adolescents with zero problem behaviors, the odds of a medically treated suicide attempt were 2.3 times greater among respondents with one, 8.8 with two, 18.3 with three, 30.8 with four, 50.0 with five, and 227.3 with six. A count of problem behaviors offers a reliable way to identify suicide risk.


Asunto(s)
Intento de Suicidio/psicología , Adolescente , Femenino , Humanos , Modelos Logísticos , Masculino , Vigilancia de la Población/métodos , Medición de Riesgo , Encuestas y Cuestionarios
14.
Exp Hematol ; 19(4): 282-7, 1991 May.
Artículo en Inglés | MEDLINE | ID: mdl-2055293

RESUMEN

Combinations of murine recombinant interleukin 3 (IL-3), purified murine macrophage colony-stimulating factor (M-CSF), and human recombinant interleukin 1 alpha (IL-1 alpha) were used to determine the effects of growth factors on the measured radiosensitivity of different populations of murine colony-forming cells (CFC). The data showed that combinations of growth factors resulted in different values of CFC radiosensitivity, being less than values observed when colony growth was stimulated using a single factor. For various combinations of growth factors, Do values ranged from 106 +/- 8 to 175 +/- 24 cGy for progenitor cells in normal bone marrow; 74 +/- 3 to 171 +/- 18 cGy for primitive multipotent CFC enriched using fluorescence-activated cell sorting; and from 46 +/- 4 to 131 +/- 10 cGy for more mature granulocyte-macrophage CFC, enriched by counterflow centrifugal elutriation. Only combinations of three factors produced the high values of Do reported in experiments using unpurified conditioned medium as a stimulus for colony formation.


Asunto(s)
Interleucina-3/farmacología , Factor Estimulante de Colonias de Macrófagos/farmacología , Tolerancia a Radiación , Células Madre/fisiología , Animales , Médula Ósea/fisiología , Combinación de Medicamentos , Femenino , Citometría de Flujo , Interleucina-3/administración & dosificación , Factor Estimulante de Colonias de Macrófagos/administración & dosificación , Masculino , Ratones , Células Madre/efectos de los fármacos
15.
Am J Prev Med ; 49(6): 930-4, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26231856

RESUMEN

INTRODUCTION: Youth with Type 1 diabetes and lower family income typically have poorer glycemic control. This post hoc analysis examines whether a family-oriented behavioral intervention for this population is differentially effective across income levels. METHODS: Families of youth aged 9-15 years with Type 1 diabetes (N=390; 49.2% female; age, 12.4 [1.7] years; hemoglobin A1c [HbA1c], 8.4 [1.2]; pump, 33.8%) at four U.S. pediatric endocrinology clinics participated in a 2-year RCT (data collected 2006-2011) of a clinic-integrated behavioral intervention designed to improve diabetes management by facilitating problem-solving skills, communication skills, and responsibility sharing. HbA1c was analyzed centrally. Family income was categorized as <$50,000 (low); $50,000 to <$100,000 (middle); and ≥$100,000 (high). Treatment effect was defined as the change in HbA1c from baseline to 2-year follow-up. A linear model tested the interaction of treatment effect with family income, controlling for race, insulin regimen, and site (analyzed in 2014). RESULTS: Baseline HbA1c was significantly poorer (p=0.004) in the low-income group. There was a significant overall effect of treatment group on change in HbA1c from baseline to follow-up (p=0.04). The interaction term for treatment by income group was not significant (p=0.44). Within each income category, a smaller deterioration in glycemic control was observed for the treatment group relative to controls. CONCLUSIONS: This clinic-integrated behavioral intervention was similarly effective in improving glycemic control among youth with Type 1 diabetes across income levels. This family-oriented problem-solving approach offers flexibility in addressing families' needs and may optimize impact on health outcomes across income groups.


Asunto(s)
Terapia Conductista , Diabetes Mellitus Tipo 1/prevención & control , Evaluación de Resultado en la Atención de Salud , Clase Social , Adolescente , Glucemia/análisis , Niño , Femenino , Humanos , Masculino , Estados Unidos
16.
Hum Gene Ther ; 2(1): 61-70, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1863641

RESUMEN

Retroviral vectors are considered to be the most suited vehicles for somatic gene therapy with hematopoietic stem cells as targets. Retrovirus-mediated gene transfer into differentiation-restricted hematopoietic precursor (FDC-P1, FDC-P2) and multipotent progenitor (stem) cell lines (FDC-Pmix) is inefficient. Two cellular restrictions are involved. One is specific for stem but not precursor cells and is at the level of transcription. Due to a unique property of the transcriptional control region of the myeloproliferative sarcoma virus (MPSV), vectors derived from MPSV are not affected by this block. The second restriction occurs before proviral DNA synthesis and integration. This inhibition of effective viral infection depends on the state of differentiation, being more pronounced in multipotent clonogenic blast cells. This block to retroviral infection affects all retroviral vectors tested.


Asunto(s)
Virus Defectuosos/genética , Regulación de la Expresión Génica , Vectores Genéticos , Células Madre Hematopoyéticas/microbiología , Virus del Sarcoma Murino de Moloney/genética , Transfección , Animales , Diferenciación Celular , Línea Celular , ADN Viral/genética , Virus Defectuosos/fisiología , Fibroblastos/metabolismo , Células Madre Hematopoyéticas/citología , Ratones , Virus del Sarcoma Murino de Moloney/fisiología , Provirus/genética , Provirus/metabolismo , Receptores Virales/metabolismo , Transcripción Genética , Transformación Genética
17.
Cancer Gene Ther ; 7(5): 721-31, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10830719

RESUMEN

Expression of the Escherichia coli enzyme nitroreductase (NTR) in mammalian cells enables them to activate the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), leading to interstrand DNA cross-linking and apoptosis in both proliferating and quiescent cells. In the work reported here, we used human hepatocellular carcinoma and squamous carcinoma cell lines constitutively expressing NTR to demonstrate that the ntr/CB1954 system results in potent, long-lasting antitumoral effects in mice. We also demonstrate that this enzyme/prodrug combination results in antitumoral effects in vivo when only a minority of tumor cells express the enzyme, using either cells constitutively expressing NTR or ntr gene delivery in situ.


Asunto(s)
Aziridinas/uso terapéutico , Escherichia coli/enzimología , Escherichia coli/genética , Neoplasias Experimentales/terapia , Nitrorreductasas/genética , Profármacos/uso terapéutico , Animales , Apoptosis , Aziridinas/toxicidad , Carcinoma Hepatocelular/terapia , Carcinoma de Células Escamosas/terapia , Reactivos de Enlaces Cruzados , Relación Dosis-Respuesta a Droga , Neoplasias de Cabeza y Cuello/terapia , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/terapia , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Necrosis , Trasplante de Neoplasias , Neoplasias Experimentales/patología , Profármacos/toxicidad , Inducción de Remisión , Factores de Tiempo , Células Tumorales Cultivadas
18.
Immunol Lett ; 16(3-4): 171-7, 1987 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-3127331

RESUMEN

We outline recent work in our laboratories on thymus progenitors, lineages within the thymus, interactions between regulatory and effector lymphocytes, splitting the CD4 (T4) T cell subset, and Ir and Is genes. We highlight the possibilities for future research opened up by the demonstration that certain marrow-derived cell lines can repopulate thymic lobes in culture, and also the deep insight into the logical structure of the lymph node provided by our ability to make an exact comparison between two-cell-type and three-cell-type immunoregulatory clusters.


Asunto(s)
Linfocitos T , Animales , Células Presentadoras de Antígenos/inmunología , Antígenos de Diferenciación de Linfocitos T , Genes MHC Clase II , Células Madre Hematopoyéticas/citología , Tolerancia Inmunológica , Ratones , Linfocitos T/clasificación , Linfocitos T/citología , Linfocitos T/inmunología
19.
Toxicol Sci ; 77(1): 135-41, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14600286

RESUMEN

The mechanisms of toxicant-mediated lung injury and repair are influenced by the considerable spatial heterogeneity that exists within the conducting airways of the lungs. As a result of this heterogeneity, significant differences and similarities in gene expression are observed throughout lung subcompartments. RNA-based technologies such as real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and cDNA microarray analysis of gene expression provide valuable clues to understanding the mechanisms of toxicant-induced injury. Isolating RNA from lung subcompartments has previously involved considerable time and labor-intensive processes that limit the number of animals that could be processed in a day. The aim of this study was to determine if intact, high-quality RNA could be preserved in situ over a period of time to delay the need to immediately perform site-specific lung subcompartment microdissections and RNA isolations. Two hours after 1-nitronaphthalene treatment, rat lungs were inflated with and stored in RNA preservation solution and stored at 4 degrees C for 7 days. RNA was isolated from the lung subcompartments isolated by microdissection. After 7 days of storage, the RNA was intact, of high quality, and could be used for real-time RT-PCR to examine heterogeneous gene expression in the lung subcompartments. In summary, this simplified technique of in situ RNA preservation and site-specific lung subcompartment microdissection allows the isolation of intact, high-quality RNA that may be used with molecular RNA-based technologies that will significantly accelerate our understanding of pulmonary injury and repair mechanisms.


Asunto(s)
Expresión Génica , Pulmón/metabolismo , ARN Mensajero/aislamiento & purificación , Conservación de Tejido/métodos , Animales , Artefactos , Cartilla de ADN/química , Sondas de ADN/química , Electroforesis en Gel de Agar , Fijadores , Expresión Génica/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Microdisección , Naftalenos/toxicidad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley
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