RESUMEN
Objective: To evaluate the risk of chronic kidney disease (CKD), cardiovascular disease (CVD), and osteoporotic fractures in human immunodeficiency virus (HIV) patients utilizing data within the Veteran's Affairs (VA) Administration system.Methods: A retrospective cohort study utilizing VA system claims (January 2000-December 2016) were extracted from the VA Informatics and Computing Infrastructure (VINCI). Cases included Veterans with an ICD-9/10 for HIV who had at least one prescription for a complete antiretroviral therapy (ART) regimen. Two non-HIV controls were exactly matched on race, sex, month, and year of birth. All patients were followed until the earliest of the following: first incidence of the outcome (identified based on diagnosis codes or laboratory data), last date of VA activity, death, or December 31, 2016. Relative risks (RR) and odds ratios (ORs) were estimated from multivariable Poisson regression models (CVD and osteoporotic fractures) and multivariable logistic regression models (CKD), respectively. Models were adjusted for demographic factors/comorbidities.Results: A total of 79,578 patients (26,526 HIV and 53,052 non-HIV) met all study criteria. The average age was 49.3 years, 38% were black, 32% were white, and 97% were male for both the HIV and control cohorts. The adjusted models demonstrated that HIV was associated with a 78% increased rate of CKD (OR = 1.78, 95% CI = 1.68-1.89), a 32% increased risk of CVD (RR = 1.32, 95% CI = 1.28-1.37), and a 38% increased risk of fractures (RR = 1.38, 95% CI = 1.23-1.56) compared to non-HIV controls.Conclusions: The risk/rate of the three outcomes were significantly higher in HIV patients compared to controls.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Infecciones por VIH/epidemiología , Fracturas Osteoporóticas/epidemiología , Insuficiencia Renal Crónica/epidemiología , Adulto , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , VeteranosRESUMEN
BACKGROUND: Longitudinal studies examining the potential mediating roles of birth weight and breastfeeding duration on the pathways between maternal gestational weight gain (GWG) and offspring anthropometric outcomes are lacking. METHODS: We analyzed data from the mother-child pairs in the Infant Feeding Practices Study II (IFPS II) in late infancy (n=1548) and at the Year 6 Follow-up (n=1514) Study. Child anthropometrics included age- and sex-specific Z-scores for weight for age (WAZ), height /length for age, weight for height/length and body mass index (BMIZ). Structural equation models were used to estimate the total, direct and indirect effects of GWG on child anthropometrics through birth weight and breastfeeding duration. RESULTS: The total effect of GWG on offspring anthropometric outcomes was significant for WAZ (ß=0.107, 95% confidence interval (CI): 0.052, 0.161) at late infancy and for WAZ (ß=0.122, 95% CI: 0.066, 0.177) and BMIZ (ß=0.120, 95% CI: 0.063, 0.178) at 6 years old. The direct effects of GWG on offspring's WAZ and BMIZ were observed only at 6 years old. The indirect effects of GWG through birth weight were significant on most of the offspring's anthropometric measures. Compared to breastfeeding duration, birth weight was a stronger mediator on the pathways between GWG and all proposed anthropometric measures both in late infancy and in early childhood. Longer duration of breastfeeding was inversely associated with all offspring anthropometric outcomes at late infancy but not with those outcomes at 6 years old. CONCLUSIONS: Our findings suggest a stronger indirect rather than direct effect of GWG on children's anthropometric outcomes mainly through birth weight, independent of maternal sociodemographic and reproductive factors. Longer duration of breastfeeding might suppress the positive relationship between GWG, birth weight and anthropometric outcomes in late infancy but not among 6 years old.
Asunto(s)
Peso al Nacer/fisiología , Lactancia Materna/estadística & datos numéricos , Desarrollo Infantil/fisiología , Ganancia de Peso Gestacional/fisiología , Embarazo/estadística & datos numéricos , Antropometría , Niño , Preescolar , Femenino , Humanos , Lactante , Estudios LongitudinalesRESUMEN
INTRODUCTION: Chronic villitis of unknown etiology (CVUE) and massive chronic intervillositis (MCI) are placental lesions associated with infiltration of mononuclear cells in the chorionic villi and the intervillous spaces, respectively. It is not well known whether immune cells in CVUE and MCI have similar phenotypic characteristics. METHODS: A cross-sectional study of third trimester placentas was conducted to identify immune cell subpopulations in CVUE and MCI (n = 17/group). CVUE was diagnosed with H&E staining and antibody to CD3 in serial sections; and MCI, by the presence of massive infiltration of mononuclear cells in the intervillous spaces. Immune cells, ICAM-1 expression and nuclear factor κB (NF-κB) activation were determined immunohistochemically. RESULTS: CVUE and MCI showed similar infiltrates, mainly CD68+ and CD3+ cells. Most cells (>80%) were CD45RB+, and one third were CD45RO+ in both lesions. There were slightly more CD8+ than CD4+ cells in both CVUE and MCI. More than 90% of cells in CVUE and MCI were ICAM-1+ with NFκB nuclear localization. Syncytiotrophoblast ICAM-1 expression was significantly (p < 0.001) higher in MCI (mean of 81.0; range of 71.6-86.0) than in CVUE (52.4; 36.4-59.4) or normal placentas (0.2; 0.0-0.6). Both, failure of physiologic transformation of spiral arteries and placental atherosclerosis-like lesions of atherosis were significantly more frequent in MCI than in CVUE or normal placentas (p = 0.044 and p = 0.007, respectively). DISCUSSION: These finding suggest that MCI and CVUE have very similar infiltration of immune cells although MCI has more severe placental lesions.
Asunto(s)
Vellosidades Coriónicas/patología , Enfermedades Placentarias/patología , Linfocitos T/patología , Trofoblastos/patología , Adolescente , Adulto , Vellosidades Coriónicas/inmunología , Vellosidades Coriónicas/metabolismo , Estudios Transversales , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , FN-kappa B/metabolismo , Enfermedades Placentarias/inmunología , Enfermedades Placentarias/metabolismo , Embarazo , Tercer Trimestre del Embarazo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Trofoblastos/inmunología , Trofoblastos/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Effective care of young people with rare conditions requires ongoing coordinated medical treatment as well as educational and social support services. However, information on treatment is often lacking due to limited data. South Carolina has a repository of comprehensive health and human service data with which individuals may be tracked across the data systems of multiple state agencies and organizations. OBJECTIVE: To develop a method for studying health care of young persons with rare conditions using this repository. METHODS: We identified individuals aged 15 to 24 years diagnosed during 2000-2010 with Fragile X syndrome (FXS), spina bifida (SB), or muscular dystrophy (MD) using a series of algorithms. ICD-9-CM codes were used to initially identify the cohort from medical billing data. Demographics, medical care, employment, education, and socioeconomic status data were then extracted from linked administrative sources. RESULTS: We identified 1,040 individuals with these rare conditions: 125 with FXS, 695 with SB, and 220 with MD. The vast majority of the cases (95%) were identified in the Medicaid database. Half of the cohort was male, with a higher percentage in the FXS and MD groups. Sixty-two percent of the cohort was enrolled in the last year of high school. Over half of the cohort received support services from the state's disability and special-needs agency; 16% received food assistance. Thirty-eight percent were employed at some point during the study period. Forty-nine individuals with SB and 56 with MD died during the study period. CONCLUSIONS: We used a linked statewide data system to study rare conditions. Strengths include the diversity of information, rigorous identification strategies, and access to longitudinal data. Despite limitations inherent to administrative data, we found that linked state data systems are valuable resources for investigating important public health questions on rare conditions.
Asunto(s)
Síndrome del Cromosoma X Frágil/epidemiología , Distrofias Musculares/epidemiología , Enfermedades Raras/epidemiología , Sistema de Registros , Disrafia Espinal/epidemiología , Gobierno Estatal , Adolescente , Femenino , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/terapia , Agencias Gubernamentales , Humanos , Masculino , Distrofias Musculares/diagnóstico , Distrofias Musculares/terapia , Enfermedades Raras/diagnóstico , Enfermedades Raras/terapia , South Carolina/epidemiología , Disrafia Espinal/diagnóstico , Disrafia Espinal/terapia , Adulto JovenRESUMEN
INTRODUCTION: Massive chronic intervillositis (MCI), also known as chronic intervillositis of unknown etiology, is a placental lesion associated with massive infiltration of mononuclear cells in the intervillous space, poor perinatal outcome, and high rate of recurrence. Our previous demonstration of increased syncytiotrophoblast (st) intercellular adhesion molecule-1 (ICAM-1) expression in villitis lesions and the finding of extensive monocyte/macrophagic cells in the maternal intervillous space in MCI, led us to further investigate stICAM-1 in MCI. MATERIALS AND METHODS: A cross-sectional study of placentas from the third trimester of pregnancy (34-41 weeks gestation) was conducted to determine stICAM-1 in MCI (n = 7). MCI stICAM-1 expression was compared to stICAM-1 in villitis (n = 7) and in normal villi from placentas with (n = 7) and without (n = 7) villitis. Maternal cells within villi in MCI were identified in placentas mismatched for maternal/fetal human leukocyte antigen (HLA)-DRw52. Villitis was diagnosed with hematoxylin and eosin staining and antibody to CD3 in serial sections, and ICAM-1 in syncytiotrophoblasts was confirmed with antibodies to ICAM-1 and cytokeratin. RESULTS: Placentas with MCI had higher stICAM-1 (79.8%) than placentas with villitis (27.1%), normal villi from placentas with villitis (11.5%), and normal villi from placentas without villitis (0.3%). Maternal cells were identified within villi of placentas (n = 5) mismatched (mothers positive, fetuses negative) for HLA-DRw52. CONCLUSIONS: Placentas with MCI have more stICAM-1 than placentas with or without villitis lacking MCI. The finding that MCI and villitis have prominent stICAM-1 and maternal cells in the villi suggests that MCI and villitis could have a similar pathophysiologic mechanism.
Asunto(s)
Vellosidades Coriónicas/metabolismo , Feto/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Enfermedades Placentarias/metabolismo , Placenta/metabolismo , Adulto , Estudios Transversales , Femenino , Feto/patología , Humanos , Inmunohistoquímica , Placenta/patología , Enfermedades Placentarias/patología , Embarazo , Adulto JovenRESUMEN
At our institution surgical correction of symptomatic flat foot deformities in children has been guided by a paradigm in which radiographs and pedobarography are used in the assessment of outcome following treatment. Retrospective review of children with symptomatic flat feet who had undergone surgical correction was performed to assess the outcome and establish the relationship between the static alignment and the dynamic loading of the foot. A total of 17 children (21 feet) were assessed before and after correction of soft-tissue contractures and lateral column lengthening, using standardised radiological and pedobarographic techniques for which normative data were available. We found significantly improved static segmental alignment of the foot, significantly improved mediolateral dimension foot loading, and worsened fore-aft foot loading, following surgical treatment. Only four significant associations were found between radiological measures of static segmental alignment and dynamic loading of the foot. Weakness of the plantar flexors of the ankle was a common post-operative finding. Surgeons should be judicious in the magnitude of lengthening of the plantar flexors that is undertaken and use techniques that minimise subsequent weakening of this muscle group.
Asunto(s)
Pie Plano/fisiopatología , Pie Plano/cirugía , Adolescente , Fenómenos Biomecánicos , Niño , Femenino , Pie Plano/diagnóstico por imagen , Humanos , Masculino , Radiografía , Estudios RetrospectivosRESUMEN
Early risk-prediction is essential to prevent cardiac allograft vasculopathy (CAV) and graft failure in heart transplant patients. We developed multivariate models to identify patients likely to experience CAV, severe CAV, and failure due to CAV, at 1, 5 and 10 years. A cohort of 172 patients was followed prospectively for 6.7 ± 3.9 years. Logistic regression models were developed and cross-validated using bootstrap resampling. Predictive markers of atherothrombosis (myocardial fibrin deposition, and loss of vascular antithrombin and tissue plasminogen activator) and arterial endothelial activation (intercellular adhesion molecule-1 expression) were measured in serial biopsies obtained within 3 months posttransplant. Most markers were univariately associated with outcome. Multivariate models showed that loss of tissue plasminogen activator was the dominant and, in most cases, only predictor of long-term CAV (p < 0.001), severe CAV (p < 0.001), and graft failure due to CAV (p < 0.001). The models discriminated patients having adverse outcomes, had particularly high negative predictive values (graft failure due to CAV: 99%, 99% and 95% at 1, 5 and 10 years) and predicted event incidence and time to event. Early absence of atherothrombotic risk identifies a patient subgroup that rarely develops CAV or graft failure, implying that this low-risk subgroup could possibly be followed with fewer invasive procedures.
Asunto(s)
Biomarcadores/metabolismo , Rechazo de Injerto/diagnóstico , Insuficiencia Cardíaca/diagnóstico , Trasplante de Corazón/efectos adversos , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/etiología , Adulto , Diagnóstico Precoz , Femenino , Rechazo de Injerto/etiología , Rechazo de Injerto/metabolismo , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/metabolismo , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Trasplante Homólogo , Enfermedades Vasculares/metabolismoRESUMEN
We have reviewed our experience of the removal of deep extremity orthopaedic implants in children to establish the nature, rate and risk of complications associated with this procedure. A retrospective review was performed of 801 children who had 1223 implants inserted and subsequently removed over a period of 17 years. Bivariate analysis of possible predictors including clinical factors, complications associated with implant insertion and indications for removal and the complications encountered at removal was performed. A logistical regression model was then constructed using those predictors which were significantly associated with surgical complications from the bivariate analyses. Odds ratios estimated in the logistical regression models were converted to risk ratios. The overall rate of complications after removal of the implant was 12.5% (100 complications in 801 patients), with 48 (6.0%) major and 52 (6.5%) minor. Children with a complication after insertion of the initial implant or with a non-elective indication for removal, a neuromuscular disease associated with a seizure disorder or a neuromuscular disease in those unable to walk, had a significantly greater chance of having a major complication after removal of the implant. Children with all four of these predictors were 14.6 times more likely to have a major complication.
Asunto(s)
Remoción de Dispositivos/métodos , Extremidades/cirugía , Dispositivos de Fijación Ortopédica , Adolescente , Índice de Masa Corporal , Parálisis Cerebral/cirugía , Niño , Preescolar , Remoción de Dispositivos/efectos adversos , Femenino , Fracturas Óseas/etiología , Humanos , Lactante , Masculino , Enfermedades Neuromusculares/cirugía , Falla de Prótesis , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: Validation-study data were analyzed to investigate the effect of retention interval (time between the to-be-reported meal and interview) on accuracy of children's school-breakfast reports and school-lunch reports in 24-h recalls, and to compare accuracy of children's school-breakfast reports for two breakfast locations (classroom; cafeteria). SUBJECTS/METHODS: Each of 374 fourth-grade children was interviewed to obtain a 24-h recall using one of six conditions from crossing two target periods (prior 24 h; previous day) with three interview times (morning; afternoon; evening). Each condition had 62 or 64 children (half boys). A recall's target period included one school breakfast and one school lunch, for which the child had been observed. Food-item variables (observed number; reported number; omission rate; intrusion rate) and energy variables (observed; reported; report rate; correspondence rate; inflation ratio) were calculated for each child for school breakfast and school lunch separately. RESULTS: Accuracy for school-breakfast reports and school-lunch reports was inversely related to retention interval. Specifically, as indicated by smaller omission rates, smaller intrusion rates, larger correspondence rates and smaller inflation ratios, accuracy for school-breakfast reports was best for prior-24-h recalls in the morning, and accuracy for school-lunch reports was best for prior-24-h recalls in the afternoon. For neither school meal was a significant sex effect found for any variable. For school-breakfast reports, there was no significant school-breakfast location effect for any variable. CONCLUSIONS: By shortening the retention interval, accuracy can be improved for school-breakfast reports and school-lunch reports in children's 24-h recalls.
Asunto(s)
Ingestión de Alimentos/psicología , Entrevistas como Asunto/métodos , Entrevistas como Asunto/normas , Recuerdo Mental , Autorrevelación , Estudiantes/psicología , Niño , Estudios Cruzados , Encuestas sobre Dietas , Femenino , Humanos , Masculino , Psicología Infantil , Reproducibilidad de los Resultados , Instituciones Académicas , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
The 5'-flanking region of the rat thrombomodulin gene was cloned by polymerase chain reaction (PCR) amplification of adaptor-ligated rat genomic DNA fragment libraries, using primers derived from the coding sequences of the thrombomodulin cDNA and adaptor primers. By sequence analysis putative regulatory elements in the promoter domain were shown to include a TATA box and several conserved binding sites for stimulatory protein 1 (SP1) and activator protein 2 (AP2). The transcription factor activator protein 1 (AP1) binding site located in the 5'-flanking region may serve as a negative gene regulatory site for tumor necrosis factor-alpha (TNF-alpha). A potential retinoic acid response element (RARE) and a possible cAMP response element are located in the putative promoter region, suggesting a role for retinoic acid and cAMP in the induction of thrombomodulin gene expression. The rat thrombomodulin gene promoter sequence shows 89% homology to that of mouse and 77% homology to that of human.
Asunto(s)
Secuencias Reguladoras de Ácidos Nucleicos , Trombomodulina/genética , Animales , Secuencia de Bases , Sitios de Unión , Clonación Molecular , Secuencia Conservada , AMP Cíclico/metabolismo , Proteínas de Unión al ADN/metabolismo , Humanos , Ratones , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Ratas , Ratas Sprague-Dawley , Elementos de Respuesta , Análisis de Secuencia de ADN , Factor de Transcripción Sp1/metabolismo , TATA Box , Trombomodulina/metabolismo , Factor de Transcripción AP-1/metabolismo , Factor de Transcripción AP-2 , Factores de Transcripción/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Thrombomodulin (TM), in addition to its significance in the protein C anticoagulant pathway and cardiovascular diseases, has recently been shown to play important roles in normal embryonic development, several inflammatory conditions, as well as in tumor biology and in the pathogenesis of chronic radiation toxicity. We cloned and sequenced the cDNA encoding the complete TM protein from the Sprague-Dawley rat. The cDNA sequence consisted of a 78-bp 5' non-coding region and a 1731-bp open reading frame encoding 577 amino acids. Comparison of the deduced amino acid sequences showed Sprague-Dawley rat TM to be 87% homologous with mouse and 70.3% with human TM. In addition to the previously described highly conserved region in the lectin-like domain, another region was found which possessed significant homology among the species and may be involved in regulating cell surface expression of TM. Primers and fluorogenic probe for 5' exonuclease-based real time RT-PCR detection (TaqMan PCR) were constructed based on the cDNA sequence information and used to determine steady-state TM mRNA levels in lung, intestine, kidney, brain, and liver. The highest TM mRNA levels were found in lung and the lowest in liver. Immunohistochemistry confirmed that TM was mainly localized on the endothelium of blood vessels and lymphatics. The alveolar capillaries of lung showed the strongest immunoreactivity, whereas the endothelium of hepatic sinusoids and cerebral cortex were virtually negative.
Asunto(s)
ADN Complementario/genética , Análisis de Secuencia de ADN , Trombomodulina/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Encéfalo/metabolismo , Clonación Molecular , Expresión Génica , Humanos , Mucosa Intestinal/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Ratones , Datos de Secuencia Molecular , Ratas , Ratas Sprague-Dawley , Homología de Secuencia de Aminoácido , Distribución TisularRESUMEN
Chronic intestinal radiation injury is associated with locally increased TGF-beta1 immunoreactivity that correlates with morphological alterations. However, the underlying mechanisms are not known. This study examined changes in intestinal TGF-beta1 immunoreactivity, steady-state TGF-beta1 mRNA levels, and cellular localization of TGF-beta1 mRNA during development of chronic radiation enteropathy in a rat model. A loop of small bowel was fixed inside the scrotum of orchiectomized male rats. The intestine was subsequently exposed locally to 0, 12 or 21 Gy X radiation. Intestine was procured at 24 h and 2, 6 and 26 weeks and subjected to histopathological analysis, quantitative immunohistochemistry with computerized image analysis, assessment of steady-state TGF-beta1 mRNA levels with quantitative reverse transcriptase polymerase chain reaction, and identification of cell types expressing TGF-beta1 mRNA with in situ hybridization. Intestine from the 21-Gy group exhibited more histopathological injury and increased TGF-beta immunoreactivity 2-26 weeks after irradiation compared to the 12-Gy group and sham-irradiated controls. TGF-beta1 mRNA in irradiated intestine increased up to six times relative to controls at 24 h and 2 weeks, was less at 6 weeks, and did not differ from controls at 26 weeks. In situ hybridization detected TGF-beta1 mRNA in epithelial and Paneth cells in control intestine. Irradiated intestine exhibited additional TGF-beta1 mRNA in inflammatory and fibroblast-like cells. We conclude that there is a radiation-induced shift in the cellular sources of TGF-beta1, and that Tgfb1 gene expression is increased mainly during the early phases of radiation enteropathy, preceding the increase in immunoreactivity and histopathological injury. Translational or post-translational mechanisms are likely involved in sustaining increased TGF-beta1 immunoreactivity levels during the chronic phase of radiation enteropathy.
Asunto(s)
Intestino Delgado/lesiones , Intestino Delgado/efectos de la radiación , Traumatismos Experimentales por Radiación/etiología , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Animales , Secuencia de Bases , Cartilla de ADN/genética , Expresión Génica , Inmunohistoquímica , Hibridación in Situ , Intestino Delgado/inmunología , Masculino , Biosíntesis de Proteínas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Traumatismos Experimentales por Radiación/genética , Traumatismos Experimentales por Radiación/inmunología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Congress plays an important role in shaping U.S. health care policy, and within Congress, committees play the lead policy-making role. To determine the range and extent of committee involvement on health issues, I examine nine health issue categories over a fifteen-year period (1979-1993) to discover how both "legislative" and "nonlegislative" committee jurisdictions differ across three dimensions: congressional chambers, committees within those chambers, and specific health issue categories. Then, to capture differences across a fourth dimension, time, I also calculate annual measures of jurisdiction "concentration" for legislative and nonlegislative jurisdictions. Together, the jurisdiction differences across the four dimensions provide a comprehensive view of congressional committee jurisdiction arrangements surrounding health issues. I find that the differences in jurisdiction across each dimension follow general patterns resulting from institution-specific factors (e.g., rules, norms) and from issue-specific factors (e.g., salience, complexity). Recognizing these dimensions and their respective patterns helps us understand the power that committees exercise over health issues.
Asunto(s)
Legislación Médica , Costos de la Atención en Salud/legislación & jurisprudencia , Reforma de la Atención de Salud/legislación & jurisprudencia , Servicios de Salud/legislación & jurisprudencia , Estados UnidosRESUMEN
Glucocorticoid regulation of expression of the protooncogene fos has been examined in AtT-20 cells at both the RNA and protein levels. When cells were incubated continuously in the presence of dexamethasone, an early (30 min) rise in the expression of fos mRNA was observed, which declined by 1 h, but rose again after 2 h of hormone treatment. Six hours after hormone treatment, fos mRNA levels had returned to control levels in spite of the continued presence of dexamethasone. Serum treatment resulted in a sustained increase in fos mRNA levels; however, the glucocorticoid and serum effects were additive. Dexamethasone and/or serum both increased the steady state levels of fos protein. Glucocorticoid treatment of AtT-20 cells results in complex changes in fos expression, but does not affect their viability or growth rate; these results suggest that fos may play a role in mediation or modulation of glucocorticoid effects other than growth.
Asunto(s)
Dexametasona/farmacología , Genes fos , Animales , Western Blotting , Células Cultivadas , Cicloheximida/farmacología , Proteínas Oncogénicas v-fos/análisis , Proteínas Oncogénicas v-fos/inmunología , Pruebas de Precipitina , Biosíntesis de Proteínas , ARN Mensajero/análisisRESUMEN
Deinococcus radiodurans genomic DNA, introduced to Escherichia coli in cloning vectors, has been reported to produce radioresistant E. coli that can be selected by gamma irradiation. In this report prior results are reassessed experimentally, and additional studies are presented. Results to date suggest that the acquired radioresistance of E. coli selected by gamma irradiation does not stem from expression of stable plasmid-encoded D. radiodurans sequences, and that acquired radioresistance is not readily transmitted to naive (unirradiated) E. coli by transformation of plasmid recovered from the radioresistant isolates. Several interpretations are discussed.
Asunto(s)
ADN Bacteriano/genética , Escherichia coli/genética , Vectores Genéticos , Bacterias Grampositivas/genética , Tolerancia a Radiación/genética , PlásmidosRESUMEN
We surveyed several human cell lines for production of alpha- and beta-human chorionic gonadotropin (hCG) under a variety of conditions known to induce gene expression. alpha- and beta-hCG subunits were monitored in culture media by specific radioimmunoassays and were shown to be quite sensitive to serum refeeding and growth state of all cell types studied. The permanent line JEG-3 secreted both alpha- and beta-subunits whereas HeLa cells secreted only the alpha-subunit. Production of both subunits was augmented in these permanent cell lines, for each growth state, by pretreating cells with 5-azacytidine; in contrast, spontaneous beta-hCG production by normal human fibroblasts (four of six strains) was only rarely increased after 5-azacytidine treatment, and more often was suppressed by 30 to 40%. Three of five strains from inherited chromosomal breakage syndromes produced immunoassayable beta-hCG spontaneously, two of which increased secretion upon treatment with either UV or mitomycin C. Surprisingly, one normal cell strain of fetal origin was induced to secrete alpha-hCG, but not beta-hCG, after UV irradiation. JEG-3 and HeLa cells produced detectable cognate mRNA for alpha- or beta-hCG subunits or both by Northern and S1 nuclease protection analyses, whereas such transcripts from untransformed human fibroblasts were consistently below detectable levels. Quantitation of beta-hCG mRNA by RNA:RNA annealing kinetics indicates that even the fibroblast strain producing the highest secreted beta-hCG levels contained cognate mRNAs at only approximately 0.1 per cell. We conclude that hCG expression in human fibroblasts is strongly repressed at the transcriptional level, although a variety of conditions (growth state, serum refeeding, cell senescence, or DNA damage) can affect the level of "leaky" expression, at least in some responding fraction of cells.
Asunto(s)
Gonadotropina Coriónica/biosíntesis , Regulación de la Expresión Génica/fisiología , Hormonas Glicoproteicas de Subunidad alfa/biosíntesis , Fragmentos de Péptidos/biosíntesis , División Celular , Supervivencia Celular/fisiología , Células Cultivadas , Gonadotropina Coriónica/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta , Daño del ADN , Fibroblastos/metabolismo , Regulación de la Expresión Génica/genética , Hormonas Glicoproteicas de Subunidad alfa/metabolismo , Humanos , Cinética , Metilación , Fragmentos de Péptidos/metabolismo , Transcripción GenéticaRESUMEN
A genomic DNA library of Deinococcus radiodurans DNA has been prepared using the plasmid vector pBR322. The recombinant plasmid was used to transform a more radiation-sensitive organism, Escherichia coli RR1. Following selection of transformed organisms by their ability to grow on ampicillin, radiation-resistant organisms were selected by irradiation with 137Cs gamma radiation. Increased radiation resistance correlates with the presence of a 3-kb fragment of DNA in these cells which is derived from D. radiodurans.
Asunto(s)
Escherichia coli/genética , Bacterias Grampositivas/genética , Tolerancia a Radiación/genética , Transformación Bacteriana/genéticaRESUMEN
Control of oncogene expression has been shown to be a coordinated regulatory mechanism in normal growth and development. Overt expression of these genes also has been noted in transformed or neoplastic cell types. The ras family of oncogenes has been shown to be particularly evident among genes expressed in malignant tissues. We provide evidence, using ribonucleic acid dot analysis and Western blot analysis of gynecologic tumor extracts, that ras expression may be a common occurrence in these malignancies. Furthermore, the ras-related peptides can be detected in sera of some patients with tumors.
Asunto(s)
Genes ras , Neoplasias de los Genitales Femeninos/genética , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Immunoblotting , Neoplasias Ováricas/genética , Pruebas de Precipitina , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , ARN Mensajero/análisis , Neoplasias Uterinas/genéticaRESUMEN
The cancer antigen CA 125 is manifest by serous cystadenocarcinoma of the ovary and to a lesser extent by other gynecologic and nongynecologic tumors. Its presence was screened for in normal human fetal tissues and fluids. Appreciable quantities of CA 125 were discovered in amniotic fluid by both a dot blot assay and the commercially available immunoradiometric assay kit. The most likely source of this antigen was found not to be the developing fetus, since antigen was absent from cord blood and fetal urine, but rather the chorionic membrane, which contained significant quantities of the antigen. CA 125 was found in extracts of maternal decidua, but none was found in extracts of placenta or amnion. The CA 125 antigen was determined by gel filtration experiments to be in excess of 700,000 daltons and probably in the range of 2 to 3 X 10(6) daltons. Size heterogeneity based on gel filtration and anion heterogeneity based on anion exchange chromatography have both been demonstrated for the CA 125 molecule. The amniotic fluid antigen is composed of two subunits of approximately 240,000 and 180,000 daltons as detected by iodine 125-labeled OC 125 monoclonal antibody. The antigen may contain additional subunits not detected by the monoclonal antibody. Size and change heterogeneity as well as the poor definition of the subunit bands on polyacrylamide gels also suggest this molecule contains an appreciable carbohydrate component.
Asunto(s)
Líquido Amniótico/inmunología , Antígenos de Neoplasias/análisis , Membranas Extraembrionarias/inmunología , Amnios/inmunología , Antígenos de Carbohidratos Asociados a Tumores , Corion/inmunología , Cromatografía , Decidua/inmunología , Electroforesis en Gel de Poliacrilamida , Femenino , Sangre Fetal/inmunología , Edad Gestacional , Humanos , Recién Nacido , Placenta/inmunología , Embarazo , Embarazo Múltiple , GemelosRESUMEN
The ductus deferens smooth muscle tumor cell line (DDT1MF-2) expresses c-sis proto-oncogene poly A+ RNA transcripts which are thought to encode at least one subunit of the potent mitogen platelet derived growth factor (PDGF). We have previously demonstrated that glucocorticoids block DDT1MF-2 cells in G0/G1 stage of the cell cycle, and that exogenously applied PDGF reinitiates cell cycle progression. In this paper we document that glucocorticoids act to inhibit cell cycle progression by inhibiting the expression of c-sis poly A+ transcripts, which we suggest are encoding a PDGF-like molecule for DDT1MF-2 cells.