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1.
Front Neurosci ; 17: 1113843, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36968508

RESUMO

Changes in ambient temperature affect all biological processes. However, these effects are process specific and often vary non-linearly. It is thus a non-trivial problem for neuronal circuits to maintain coordinated, functional output across a range of temperatures. The cardiac nervous systems in two species of decapod crustaceans, Homarus americanus and Cancer borealis, can maintain function across a wide but physiologically relevant temperature range. However, the processes that underlie temperature resilience in neuronal circuits and muscle systems are not fully understood. Here, we demonstrate that the non-isolated cardiac nervous system (i.e., the whole heart: neurons, effector organs, intrinsic feedback systems) in the American lobster, H. americanus, is more sensitive to warm temperatures than the isolated cardiac ganglion (CG) that controls the heartbeat. This was surprising as modulatory processes known to stabilize the output from the CG are absent when the ganglion is isolated. One source of inhibitory feedback in the intact cardiac neuromuscular system is nitric oxide (NO), which is released in response to heart contractions. We hypothesized that the greater temperature tolerance observed in the isolated CG is due to the absence of NO feedback. Here, we demonstrate that applying an NO donor to the isolated CG reduces its temperature tolerance. Similarly, we show that the NO synthase inhibitor L-nitroarginine (LNA) increases the temperature tolerance of the non-isolated nervous system. This is sufficient to explain differences in temperature tolerance between the isolated CG and the whole heart. However, in an intact lobster, the heart and CG are modulated by an array of endogenous peptides and hormones, many of which are positive regulators of the heartbeat. Many studies have demonstrated that excitatory modulators increase temperature resilience. However, this neuromuscular system is regulated by both excitatory and inhibitory peptide modulators. Perfusing SGRNFLRFamide, a FLRFamide-like peptide, through the heart increases the non-isolated nervous system's tolerance to high temperatures. In contrast, perfusing myosuppressin, a peptide that negatively regulates the heartbeat frequency, decreases the temperature tolerance. Our data suggest that, in this nervous system, positive regulators of neural output increase temperature tolerance of the neuromuscular system, while modulators that decrease neural output decrease temperature tolerance.

2.
J Mol Cell Cardiol ; 170: 34-46, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35661621

RESUMO

AIMS: Cardiac contractility, essential to maintaining proper cardiac output and circulation, is regulated by G protein-coupled receptor (GPCR) signaling. Previously, the absence of regulator of G protein signaling (RGS) 2 and 5, separately, was shown to cause G protein dysregulation, contributing to modest blood pressure elevation and exaggerated cardiac hypertrophic response to pressure-overload. Whether RGS2 and 5 redundantly control G protein signaling to maintain cardiovascular homeostasis is unknown. Here we examined how the dual absence of RGS2 and 5 (Rgs2/5 dbKO) affects blood pressure and cardiac structure and function. METHODS AND RESULTS: We found that Rgs2/5 dbKO mice showed left ventricular dilatation at baseline by echocardiography. Cardiac contractile response to dobutamine stress test was sex-dependently reduced in male Rgs2/5 dbKO relative to WT mice. When subjected to surgery-induced stress, male Rgs2/5 dbKO mice had 75% mortality within 72-96 h after surgery, accompanied by elevated baseline blood pressure and decreased cardiac contractile function. At the cellular level, cardiomyocytes (CM) from Rgs2/5 dbKO mice showed augmented Ca2+ transients and increased incidence of arrhythmia without augmented contractile response to electrical field stimulation (EFS) and activation of ß-adrenergic receptors (ßAR) with isoproterenol. Dual loss of Rgs2 and 5 suppressed forskolin-induced cAMP production, which was restored by Gi/o inactivation with pertussis toxin that also reduced arrhythmogenesis during EFS or ßAR stimulation. Cardiomyocyte NCX and PMCA mRNA expression was unaffected in Rgs2/5 dbKO male mice. However, there was an exaggerated elevation of EFS-induced cytoplasmic Ca2+ in the presence of SERCA blockade with thapsigargin. CONCLUSIONS: We conclude that RGS2 and 5 promote normal ventricular rhythm by coordinating their regulatory activity towards Gi/o signaling and facilitating cardiomyocyte calcium handling.


Assuntos
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP , Miócitos Cardíacos , Proteínas RGS , Animais , Arritmias Cardíacas/metabolismo , Cardiomegalia/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Masculino , Camundongos , Miócitos Cardíacos/metabolismo , Proteínas RGS/genética , Proteínas RGS/metabolismo , Transdução de Sinais
3.
J Craniofac Surg ; 31(7): 2088-2091, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32649556

RESUMO

Spring-assisted surgery (SAS) has been shown to be an effective technique for correction of isolated sagittal craniosynostosis in patients less than 6 months of age. At their institution, the authors adopted a minimally invasive technique in 2010, using a shorter incision and an endoscope. A retrospective chart review of 101 patients with isolated, nonsyndromic, sagittal craniosynostosis, who underwent SAS, was performed in order to compare perioperative and clinical outcomes of the open (n = 51) and minimally-invasive (n = 50) approaches. Surgeries were performed by 2 neurosurgeons and 3 plastic surgeons, between 2005 and 2018. The pre and postoperative cephalic indices were not significantly different in both groups. Minimally-invasive spring placement required a longer operative time than the open approach, with the mean minimally-invasive operative time at 65 minutes, compared to 53 minutes (P < 0.0001). Spring removal operative time was not significantly different, with the minimally-invasive operative time at 31 minutes versus 29 minutes (P = 0.48). There were no significant differences in major or minor complications when comparing the open and minimally-invasive approaches. In conclusion, both the open and the minimally-invasive SAS techniques are effective for early correction of isolated sagittal craniosynostosis, although the minimally-invasive approach requires a longer operative time for spring placement.


Assuntos
Craniossinostoses/cirurgia , Craniotomia , Humanos , Lactente , Neuroendoscopia/métodos , Complicações Pós-Operatórias , Procedimentos de Cirurgia Plástica , Estudos Retrospectivos , Equipamentos Cirúrgicos , Resultado do Tratamento
4.
Plast Reconstr Surg ; 146(4): 833-841, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32590513

RESUMO

BACKGROUND: Spring-assisted surgery is an accepted alternative to cranial vault remodeling for treatment of sagittal craniosynostosis. The long-term safety and efficacy profiles of spring-assisted surgery have not been established. METHODS: This study is a retrospective examination of all patients treated with spring-assisted surgery (n = 175) or cranial vault remodeling (n = 50) for sagittal craniosynostosis at the authors' institution from 2003 to 2017. Data collected included demographic and operative parameters, preoperative and postoperative Cephalic Indices, and complications. Whitaker grades were assigned blindly by a craniofacial surgeon not involved in patients' care. RESULTS: The mean age at surgery was significantly lower for the spring-assisted surgery group compared with the cranial vault remodeling group (4.6 months versus 22.2 months; p < 0.001). Even when combining spring placement with spring removal operations, total surgical time (71.1 minutes versus 173.5 minutes), blood loss (25.0 ml versus 111.2 ml), and hospital stays (41.5 hours versus 90.0 hours) were significantly lower for the spring-assisted surgery cohort versus the cranial vault remodeling group (p < 0.001 for all). There were no differences in infection, reoperation rate, or headaches between the groups. The percentage improvement in Cephalic Index was not significantly different at 1 (p = 0.13), 2 (p = 0.99), and 6 (p = 0.86) years postoperatively. At 12 years postoperatively, the spring-assisted surgery group had persistently improved Cephalic Index (75.7 preoperatively versus 70.7 preoperatively). Those undergoing spring-assisted surgery had significantly better Whitaker scores, indicating less need for revision surgery, compared with the cranial vault remodeling group (p = 0.006). CONCLUSION: Compared with the authors' cranial vault remodeling technique, spring-assisted surgery requires less operating room time and is associated with less blood loss, but it has equivalent long-term Cephalic Indices and subjectively better shape outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Craniossinostoses/cirurgia , Crânio/cirurgia , Humanos , Lactente , Procedimentos Ortopédicos/instrumentação , Procedimentos Ortopédicos/métodos , Procedimentos de Cirurgia Plástica/instrumentação , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
5.
Biometals ; 32(3): 545-561, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31209680

RESUMO

Oncolytic viruses rewire the immune system and can lead to long-lasting antitumor defenses against primary and metastatic tumors. However, results from clinical studies have shown heterogeneity in responses suggesting that multiplexed approaches may be necessary to consistently generate positive outcomes in patients. To this end, we explored the combination of oncolytic rhabdovirus VSV∆51 with vanadium(V) dipicolinate derivatives, which have already been explored for their antidiabetic properties in animal models. The combination of vanadium-based dipicolinate compounds with VSV∆51 significantly increased viral replication and cytotoxicity in the human renal cell carcinoma cell line 786-0. The effects of three vanadium(V)-dipicolinate coordination complexes ([VO2dipic]-, [VO2dipic-OH]- and [VO2dipic-Cl]- with -OH or -Cl in the para position) were compared to that of the simple salts using spectroscopy and speciation profiles. Like the vanadate salts and the vanadyl cation, all dioxovanadium(V) dipicolinate complexes tested were found to increase viral infection and cytotoxicity when used in combination with VSV∆51. Viral sensitization is dependent on the vanadium since free dipicolinate ligands exerted no effect on viral infection and viability. The ability of these complexes to interact with interfaces and the stability of the complexes were evaluated under physiological conditions. Results indicate that these complexes undergo hydrolysis in cell culture media thereby generating vanadate. The vanadium dipicolinate derivatives in the context of immunovirotherapy shares similarities with previous studies exploring the antidiabetic properties of the compounds. The synergy between vanadium compounds and the oncolytic virus suggests that these compounds may be valuable in the development of novel and effective pharmaco-viral therapies.


Assuntos
Antivirais/farmacologia , Complexos de Coordenação/farmacologia , Terapia Viral Oncolítica , Vírus Oncolíticos/efeitos dos fármacos , Ácidos Picolínicos/farmacologia , Compostos de Vanádio/farmacologia , Viroses/terapia , Antivirais/síntese química , Antivirais/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Humanos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ácidos Picolínicos/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Compostos de Vanádio/química , Viroses/tratamento farmacológico
6.
J Neurosci ; 38(17): 4146-4162, 2018 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-29610439

RESUMO

Cardiovascular disease and susceptibility to infection are leading causes of morbidity and mortality for individuals with spinal cord injury (SCI). A major contributor to these is autonomic dysreflexia (AD), an amplified reaction of the autonomic nervous system (hallmarked by severe hypertension) in response to sensory stimuli below the injury. Maladaptive plasticity of the spinal sympathetic reflex circuit below the SCI results in AD intensification over time. Mechanisms underlying this maladaptive plasticity are poorly understood, restricting the identification of treatments. Thus, no preventative treatments are currently available. Neuroinflammation has been implicated in other pathologies associated with hyperexcitable neural circuits. Specifically, the soluble form of TNFα (sTNFα) is known to play a role in neuroplasticity. We hypothesize that persistent expression of sTNFα in spinal cord underlies AD exacerbation. To test this, we intrathecally administered XPro1595, a biologic that renders sTNFα nonfunctional, after complete, high-level SCI in female rats. This dramatically attenuated the intensification of colorectal distension-induced and naturally occurring AD events. This improvement is mediated via decreased sprouting of nociceptive primary afferents and activation of the spinal sympathetic reflex circuit. We also examined peripheral vascular function using ex vivo pressurized arterial preparations and immune function via flow cytometric analysis of splenocytes. Diminishing AD via pharmacological inhibition of sTNFα mitigated ensuing vascular hypersensitivity and immune dysfunction. This is the first demonstration that neuroinflammation-induced sTNFα is critical for altering the spinal sympathetic reflex circuit, elucidating a novel mechanism for AD. Importantly, we identify the first potential pharmacological, prophylactic treatment for this life-threatening syndrome.SIGNIFICANCE STATEMENT Autonomic dysreflexia (AD), a disorder that develops after spinal cord injury (SCI) and is hallmarked by sudden, extreme hypertension, contributes to cardiovascular disease and susceptibility to infection, respectively, two leading causes of mortality and morbidity in SCI patients. We demonstrate that neuroinflammation-induced expression of soluble TNFα plays a critical role in AD, elucidating a novel underlying mechanism. We found that intrathecal administration after SCI of a biologic that inhibits soluble TNFα signaling dramatically attenuates AD and significantly reduces AD-associated peripheral vascular and immune dysfunction. We identified mechanisms behind diminished plasticity of neuronal populations within the spinal sympathetic reflex circuit. This study is the first to pinpoint a potential pharmacological, prophylactic strategy to attenuate AD and ensuing cardiovascular and immune dysfunction.


Assuntos
Disreflexia Autonômica/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Animais , Disreflexia Autonômica/fisiopatologia , Células Cultivadas , Feminino , Artérias Mesentéricas/fisiopatologia , Ratos , Ratos Wistar , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Baço/imunologia , Baço/fisiopatologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia
7.
Environ Int ; 107: 154-162, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28735152

RESUMO

BACKGROUND: Black carbon (BC) is a ubiquitous component of particulate matter (PM) emitted from combustion-related sources and is associated with a number of health outcomes. OBJECTIVES: We conducted a systematic review to evaluate the potential for cardiovascular morbidity and mortality following exposure to ambient BC, or the related component elemental carbon (EC), in the context of what is already known about the associations between exposure to fine particulate matter (PM2.5) and cardiovascular health outcomes. DATA SOURCES: We conducted a stepwise systematic literature search of the PubMed database and employed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting our results. STUDY ELIGIBILITY CRITERIA: Studies meeting inclusion criteria (i.e., include a quantitative measurement of BC or EC used to characterize exposure and an effect estimate of the association of the exposure metric with ED visits, hospital admissions, or mortality due to cardiovascular disease) were evaluated for risk of bias in study design and results. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias evaluations assess some aspects of internal validity of study findings based on study design, conduct, and reporting and identify potential issues related to confounding or other biases. RESULTS: The results of our systematic review demonstrate similar results for BC or EC and PM2.5; that is, a generally modest, positive association of each pollutant measurement with cardiovascular emergency department visits, hospital admissions, and mortality. There is no clear evidence that health risks are greater for either BC or EC when compared to one another, or when either is compared to PM2.5. LIMITATIONS: We were unable to adequately evaluate the role of copollutant confounding or differential spatial heterogeneity for BC or EC compared to PM2.5. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Overall, the evidence at present indicates that BC or EC is consistently associated with cardiovascular morbidity and mortality but is not sufficient to conclude that BC or EC is independently associated with these effects rather than being an indicator for PM2.5 mass. SYSTEMATIC REVIEW REGISTRATION NUMBER: Not available.


Assuntos
Poluentes Atmosféricos/análise , Doenças Cardiovasculares/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Fuligem/análise , Poluição do Ar/análise , Carbono/análise , Humanos
8.
Regul Toxicol Pharmacol ; 88: 332-337, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28526659

RESUMO

To inform regulatory decisions on the risk due to exposure to ambient air pollution, consistent and transparent communication of the scientific evidence is essential. The United States Environmental Protection Agency (U.S. EPA) develops the Integrated Science Assessment (ISA), which contains evaluations of the policy-relevant science on the effects of criteria air pollutants and conveys critical science judgments to inform decisions on the National Ambient Air Quality Standards. This article discusses the approach and causal framework used in the ISAs to evaluate and integrate various lines of scientific evidence and draw conclusions about the causal nature of air pollution-induced health effects. The framework has been applied to diverse pollutants and cancer and noncancer effects. To demonstrate its flexibility, we provide examples of causality judgments on relationships between health effects and pollutant exposures, drawing from recent ISAs for ozone, lead, carbon monoxide, and oxides of nitrogen. U.S. EPA's causal framework has increased transparency by establishing a structured process for evaluating and integrating various lines of evidence and uniform approach for determining causality. The framework brings consistency and specificity to the conclusions in the ISA, and the flexibility of the framework makes it relevant for evaluations of evidence across media and health effects.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Monóxido de Carbono/toxicidade , Causalidade , Humanos , Chumbo/toxicidade , Óxidos de Nitrogênio/toxicidade , Ozônio/toxicidade , Estados Unidos , United States Environmental Protection Agency
9.
Infant Child Dev ; 25(4): 339-351, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27516728

RESUMO

We examined the longitudinal associations between prenatal tobacco smoke exposure (PSE) and attention-deficit hyperactivity disorder (ADHD) symptom domains in adolescence and young adulthood. A sample of girls with ADHD combined presentation (N=93), ADHD predominantly inattentive presentation (N=47), and matched comparisons (N= 88) was assessed prospectively. Symptoms of hyperactivity/impulsivity (HI), inattention (IA), and oppositionality (oppositional defiant disorder) were measured via multiple informants 5 (M age =14 years; retention rate =92%) and 10 years (M age =20 years; retention rate =95%) following childhood ascertainment. PSE was captured via maternal self-report. We used linear regressions to examine the prediction from PSE to both HI and IA in adolescence and early adulthood after stringent control of relevant confounding variables. PSE significantly predicted HI during adolescence and young adulthood across multiple informants but did not predict IA at either wave. Symptoms of HI may have partial etiological independence from IA symptoms.

10.
Int J Public Health ; 58(5): 707-24, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23892931

RESUMO

OBJECTIVES: Recent interest has developed in understanding the health effects attributable to different components of particulate matter. This review evaluates the effects of black carbon (BC) on cardiovascular disease in individuals with pre-existing disease using evidence from epidemiologic and experimental studies. METHODS: A systematic literature search was conducted to identify epidemiologic and experimental studies examining the relationship between BC and cardiovascular health effects in humans with pre-existing diseases. Nineteen epidemiologic and six experimental studies were included. Risk of bias was evaluated for each study. RESULTS: Evidence across studies suggested ambient BC is associated with changes in subclinical cardiovascular health effects in individuals with diabetes and coronary artery disease (CAD). Limited evidence demonstrated that chronic respiratory disease does not modify the effect of BC on cardiovascular health. CONCLUSIONS: Results in these studies consistently demonstrated that diabetes is a risk factor for BC-related cardiovascular effects, including increased interleukin-6 and ECG parameters. Cardiovascular effects were associated with BC in individuals with CAD, but few comparisons to individuals without CAD were provided in the literature.


Assuntos
Poluição do Ar/análise , Doenças Cardiovasculares/epidemiologia , Exposição Ambiental/análise , Material Particulado/análise , Fuligem/análise , Asma/epidemiologia , Diabetes Mellitus/epidemiologia , Humanos , Saúde Pública , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Medição de Risco
11.
J Clin Child Adolesc Psychol ; 42(6): 762-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23581554

RESUMO

Among two large, independent samples of girls with attention-deficit/hyperactivity disorder (ADHD), we examined associations between specific (maternal gestational smoking and drug use, early labor, low birth weight, and infant breathing problems at birth) and cumulative prenatal and perinatal risk factors and psychiatric comorbidity during childhood. Data from the (a) Multimodal Treatment Study of Children with ADHD, a randomized clinical trial with 579 children aged 7 to 9.9 years with combined-type ADHD, and the (b) Berkeley Girls ADHD Longitudinal Sample, a naturalistic study of 140 girls with ADHD (93 combined-type and 47 inattentive-type) who were first seen when they were 6 to 12 years old, were analyzed separately. In each sample, perinatal risk factors were assessed retrospectively by maternal report, and current childhood psychiatric comorbidity was assessed using maternal report on the Diagnostic Interview Schedule for Children. Consistent findings across these two studies show that infant breathing problems, early labor, and total perinatal problems predicted childhood comorbid depression but not comorbid anxiety or externalizing disorders. These associations remained significant, in both samples, with control of family socioeconomic status (SES) and maternal symptoms of ADHD and depression. Results attenuated slightly with control of the number of child comorbidities plus SES and maternal symptoms. Accumulating evidence suggests that perinatal risk factors are important precursors of childhood psychiatric comorbidity and that the association between these risk factors and detrimental psychiatric outcomes cannot be explained by maternal psychiatric symptoms or SES during childhood.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtornos Mentais/epidemiologia , Mães/psicologia , Efeitos Tardios da Exposição Pré-Natal , Ansiedade/epidemiologia , Criança , Comorbidade , Depressão/epidemiologia , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Mães/estatística & dados numéricos , Trabalho de Parto Prematuro/epidemiologia , Gravidez , Transtornos Respiratórios/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Classe Social , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
12.
Am J Surg ; 198(4): 575-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19800471

RESUMO

BACKGROUND: The value of breast self-examination (BSE) to detect early breast cancer is controversial. METHODS: Within an institutional review board-approved prospective study, 147 high-risk women were enrolled from 2004 to 2007. Yearly clinical examination, BSE teaching, and mammography were performed simultaneously followed by interval breast magnetic resonance imaging (MRI). Women underwent additional BSE teaching at 6 months. Women reporting a mass on BSE underwent clinical evaluation. RESULTS: Fourteen breast cancers were detected in 12 women. BSE detected 6/14 breast cancers versus 6/14 detected by MRI and 2/14 by mammography. Of 24 masses detected by BSE, 6/24 were malignant. The sensitivity, specificity, and predictive value of BSE to detect breast cancer were 58.3%, 87.4%, and 29.2%, respectively. The sensitivity, specificity, and predictive value of a Breast Image Reporting and Data System (BI-RADS) score of >or=4 on MRI were 66.7%, 88.9%, and 34.8%, respectively. CONCLUSIONS: BSE detects new breast cancers in high-risk women undergoing screening mammogram, CBE, and yearly breast MRI.


Assuntos
Neoplasias da Mama/diagnóstico , Autoexame de Mama , Adulto , Estudos de Coortes , Detecção Precoce de Câncer , Feminino , Humanos , Imageamento por Ressonância Magnética , Mamografia , Pessoa de Meia-Idade , Estudos Prospectivos
13.
J Proteome Res ; 8(7): 3675-88, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19459691

RESUMO

Elucidation of protein-protein interactions can provide new knowledge on protein function. Enrichments of affinity-tagged (or "bait") proteins with interaction partners generally include background, nonspecific protein artifacts. Furthermore, in vivo bait expression may introduce additional artifacts arising from altered physiology or metabolism. In this study, we compared these effects for chromosome and plasmid encoding strategies for bait proteins in two microbes: Escherichia coli and Rhodopseudomonas palustris. Differential metabolic labeling of strains expressing bait protein relative to the wild-type strain in each species allowed comparison by liquid chromatography tandem mass spectrometry (LC-MS-MS). At the local level of the protein complex, authentic interacting proteins of RNA polymerase (RNAP) were successfully discerned from artifactual proteins by the isotopic differentiation of interactions as random or targeted (I-DIRT, Tackett, A. J.; et al. J. Proteome Res. 2005, 4, 1752-1756). To investigate global effects of bait protein production, we compared proteomes from strains harboring a plasmid encoding an affinity-tagged subunit (RpoA) of RNAP with the corresponding wild-type strains. The RpoA abundance ratios of 0.8 for R. palustris and 1.7 for E. coli in plasmid strains versus wild-type indicated only slightly altered expression. While most other proteins also showed no appreciable difference in abundance, several that did show altered levels were involved in amino acid metabolism. Measurements at both local and global levels proved useful for evaluating in vitro and in vivo artifacts of plasmid-encoding strategies for bait protein expression.


Assuntos
Isótopos/química , Metabolômica/métodos , Proteômica/métodos , Cromatografia Líquida/métodos , Cromossomos , RNA Polimerases Dirigidas por DNA/química , Escherichia coli/metabolismo , Íons , Espectrometria de Massas/métodos , Peptídeos/química , Plasmídeos/metabolismo , Proteínas/química , Proteoma , Rodopseudomonas/metabolismo
14.
Cancer Epidemiol Biomarkers Prev ; 18(5): 1379-85, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19383884

RESUMO

BACKGROUND: Random periareolar fine needle aspiration (RPFNA) is a research technique developed to assess short-term breast cancer risk in women at increased risk of breast cancer. Although there is increasing acceptance of RPFNA, neither the reproducibility nor the inter-institutional compatibility of RPFNA has been established. To address these key limitations, the Cancer and Leukemia Group B (CALGB) Prevention Group tested the reproducibility of RPFNA in a multi-institutional cross-sectional study. METHODS: Sixty-three high-risk women from five CALGB institutions (Duke, Ohio State, Roswell Park, Dana Farber, and Vermont) underwent RPFNA from July 1, 2007 to June 30, 2008. Duplicate bilateral RPFNA was performed on each woman by a single investigator on a single day. Masood Cytology Index score was assessed by a single blinded cytopathologist. RESULTS: There was a high degree of statistical agreement in the Masood Cytology Index scores of duplicate RPFNA samples from the same breast, with a Spearman correlation coefficient of 0.8312 (P < 0.0001). Importantly, although there was agreement in duplicate samples from the same breast, there was lack of agreement between duplicate samples from the opposite breast. CONCLUSIONS: This multi-institutional study shows that RPFNA is a highly reproducible measure of breast cytology in a cooperative group cross-sectional trial. RPFNA did not show a high degree of agreement between breasts, suggesting that breast cancer risk and progression may occur at different rates in individual breasts from a single woman. These studies provide proof-of-principle for future RPFNA-based cooperative group prevention studies.


Assuntos
Biópsia por Agulha Fina , Neoplasias da Mama/diagnóstico , Adulto , Análise de Variância , Neoplasias da Mama/patologia , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Mamilos , Reprodutibilidade dos Testes , Medição de Risco/métodos
15.
Bull Environ Contam Toxicol ; 83(1): 4-7, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19214356

RESUMO

Dietary changes are an attractive means of protecting against environmental chemical exposure. Exposure to benzo[a]pyrene (B[a]P) is a risk factor for cardiovascular disease events. It has recently been shown that B[a]P can increase intercellular adhesion molecule-1 (ICAM-1) in endothelial cells, a possible means of promoting cardiovascular disease. This study investigated the ability of flavonoids to protect against B[a]P-induced ICAM-1. It was shown that only flavonoids that contain a 4' B-ring hydroxyl substitution and a 2-3 C-ring double bond were protective. These data suggest that selected bioactive compounds can decrease proinflammatory properties of environmental chemicals such as B[a]P.


Assuntos
Antioxidantes/farmacologia , Benzo(a)pireno/toxicidade , Carcinógenos Ambientais/toxicidade , Flavonoides/farmacologia , Molécula 1 de Adesão Intercelular/biossíntese , Antioxidantes/química , Células Cultivadas , Citoproteção , Dieta , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Flavonoides/química , Humanos , Modelos Biológicos
16.
Mutat Res ; 613(1): 17-64, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16828334

RESUMO

From a literature survey, 86 chemicals are tabulated that have been evaluated in 121 assays for their clastogenic effects in Zea mays. Eighty-one of the 86 chemicals are reported as giving a positive reaction (i.e. causing chromosome aberrations). Of these, 36 are reported positive with a dose response. In addition, 32 assays have been recorded for 7 types of radiation, all of which reacted positively. The results of 126 assays with 63 chemicals and 12 types of radiation tested for the inductions of gene mutations are tabulated, as well as 63 chemicals and/or radiation in combined treatments. Three studies reported positive results for mutations on Zea mays seed sent on space flights. The Zea mays (2n=20) assay is a very good plant bioassay for assessing chromosome damage both in mitosis and meiosis and for somatic mutations induced by chemicals and radiations. The carcinogenicity and Salmonella assays correlate in all cases. The maize bioassay has been shown to be as sensitive and as specific an assay as other plant genotoxicity assays, such as Hordeum vulgare, Vicia faba, Crepis capillaris, Pisum sativum, Lycopersicon esculentum and Allium cepa and should be considered in further studies in assessing clastogenicity. Tests using Zea mays can be made for a spectrum of mutant phenotypes of which many are identifiable in young seedlings.


Assuntos
Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Zea mays/efeitos dos fármacos , Zea mays/efeitos da radiação , Bioensaio , Cariotipagem , Metanálise como Assunto , Zea mays/genética
17.
IEEE Trans Nanobioscience ; 4(2): 196-200, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16117027

RESUMO

Photosynthetic reaction centers are integral plant membrane protein complexes and molecular photovoltaic structures. We report here that addition of Photosystem I (PSI)-proteoliposomes to retinoblastoma cells imparts photosensitivity to these mammalian cells, as demonstrated by light-induced movement of calcium ions. Control experiments with liposomes lacking PSI demonstrated no photosensitivity. The data demonstrate that PSI, a nanoscale molecular photovoltaic structure extracted from plants, can impart a photoresponse to mammalian cells in vitro.


Assuntos
Sinalização do Cálcio/fisiologia , Complexo de Proteína do Fotossistema I/metabolismo , Complexo de Proteína do Fotossistema I/efeitos da radiação , Folhas de Planta/metabolismo , Retina/metabolismo , Retina/efeitos da radiação , Spinacia oleracea/metabolismo , Sinalização do Cálcio/efeitos da radiação , Linhagem Celular , Relação Dose-Resposta à Radiação , Humanos , Luz , Fotobiologia/métodos , Doses de Radiação
18.
Rev Environ Health ; 20(1): 1-13, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15835495

RESUMO

Seven higher plant species (Allium cepa, Arabidopsis thaliana, Glycine max, Hordeum vulgaris. Tradescantia paludosa, Vicia faba, and Zea mays) were reviewed for their ability to detect genotoxicity of chemical agents under the U.S. Environmental Protection Agency (U.S. EPA) Gene-Tox program in the late 1970s. Six bioassays-Allium and Vicia root tip chromosome breaks, Tradescantia chromosome break, Tradescantia micronucleus, Tradescantia-stamen-hair mutation, and Arabidopsis-mutation bioassays- were established from four plant systems that are currently in use for detecting the genotoxicity of environmental agents. Under the Gene-Tox program, the Crepis capillaris-chromosome-aberration test was added to the existing six bioassays. The current review is limited to chemical agents that exhibit a positive response to any of these seven plant bioassays. From 158 articles reviewed, 84 chemicals were compiled in three categories: carcinogens, clastogens, and mutagens. As none of these plant bioassays can detect tumor initiation or cancerous growth, the chemicals were categorized as carcinogens based on their characteristics defined by the U.S. EPA's Superfund Priority 1 List and/or by the chemical listings of the Sigma and Aldrich Chemical Companies. Certain mutagens were categorized in the same manner in addition to the agents detected as mutagens by these plant bioassays.


Assuntos
Carcinógenos/toxicidade , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Plantas/genética , Bioensaio/métodos , Aberrações Cromossômicas , Dano ao DNA , Plantas/efeitos dos fármacos
19.
Mutat Res ; 511(3): 207-37, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12088718

RESUMO

From a literature survey, 21 chemicals are tabulated that have been evaluated in 39 assays for their clastogenic effects in Lycopersicon. Nineteen of the 21 chemicals are reported as giving a positive reaction (i.e. causing chromosome aberrations). Of these, five are reported positive with a dose response. In addition, 23 assays have been recorded for six types of radiation, all of which reacted positively. The results of 102 assays with 32 chemicals and seven types of radiation tested for the induction of gene mutations are tabulated, as well as 20 chemicals and/or radiation in combined treatments. The Lycopersicon esculentum (2n=24) assay is a very good plant bioassay for assessing chromosome damage both in mitosis and meiosis and for somatic mutations induced by chemicals and radiations. The Lycopersicon bioassay has been shown to be as sensitive and as specific an assay as other plant genotoxicity assays, such as Hordeum vulgare, Vicia faba, Crepis capillaris, Pisum sativum and Allium cepa and should be considered in further studies in assessing clastogenicity. Tests using L. esculentum can be made for a spectrum of mutant phenotypes of which many are identifiable in young seedlings.


Assuntos
Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/efeitos da radiação , Aberrações Cromossômicas , Poluentes Ambientais/toxicidade , Cariotipagem , Solanum lycopersicum/genética , Mutação , Poliploidia , Sementes/efeitos dos fármacos , Sementes/genética , Sementes/efeitos da radiação , Especificidade da Espécie
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