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1.
J Contin Educ Nurs ; 54(1): 16-24, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36595722

RESUMO

Background Many infants admitted to the neonatal intensive care unit (NICU) have genetic conditions. Previous research has shown that gaps exist in the genetics knowledge of nurses and that they lack comfort applying genetics information to clinical practice. Studies assessing the knowledge or comfort of NICU nurses with genetics have not previously been completed. Method A total of 122 NICU nurses completed a survey assessing perceived knowledge of genetics, comfort with clinical scenarios involving genetics, and desired genetics education. Results Perceived knowledge and overall comfort were correlated with highest degree received, how prepared a nurse felt by the genetics education received in their training, and having a close relationship with someone with a genetic condition. Almost all respondents (96%, n = 117) desired additional genetics education. Conclusion Gaps exist in the genetics knowledge of neonatal nurses in our cohort, and their overall comfort working with clinical scenarios involving genetics was low. There is significant interest in additional genetics education. [J Contin Educ Nurs. 2023;54(1):16-24.].


Assuntos
Unidades de Terapia Intensiva Neonatal , Enfermeiras e Enfermeiros , Recém-Nascido , Lactente , Humanos , Inquéritos e Questionários , Escolaridade , Competência Clínica
2.
J Nutr Gerontol Geriatr ; 41(2): 160-174, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34919015

RESUMO

Excessive sodium consumption is a public health issue and congregate meal programs provide a unique opportunity to reduce sodium served to a large, at-risk population. A Sodium Reduction Initiative (SRI) was implemented in a congregate meal program that serves over 3,000 older adults. Nutrient analyses conducted at baseline and post-intervention were used to calculate average sodium reduction and the number of low sodium foods; targeted foods were categorized by strategy. Customer satisfaction surveys were collected at baseline and 3- and 6-months post-intervention. Kruskal Wallis and analysis of variance were used to compare sodium reduction differences. Chi-square analysis determined associations among strategies. The SRI impacted 55 foods, low sodium foods increased by 22%, and the average sodium per menu cycle was reduced by 21%. Replacement with a lower sodium food was the most frequently used strategy and had the largest sodium reduction. Sauces and main entrees were most frequently impacted, and thirteen ingredients accounted for 75% of all reduced-sodium foods. Over 50% of the 1,424 survey respondents consumed the reduced-sodium foods and food satisfaction remained stable from baseline to post-intervention. Congregate meals programs that target commonly used foods and key ingredients can significantly reduce sodium served to older adults.


Assuntos
Serviços de Alimentação , Idoso , Humanos , Refeições , Sódio
3.
Am J Med Genet A ; 185(8): 2434-2444, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34056838

RESUMO

Cantú syndrome (CS) is caused by pathogenic variants in ABCC9 and KCNJ8 encoding the regulatory and pore-forming subunits of ATP-sensitive potassium (KATP ) channels. CS is characterized by congenital hypertrichosis, distinctive facial features, peripheral edema, and cardiac and neurodevelopmental abnormalities. Behavioral and cognitive issues have been self-reported by some CS individuals, but results of formal standardized investigations have not been published. To assess the cognitive profile, social functioning, and psychiatric symptoms in a large group of CS subjects systematically in a cross-sectional manner, we invited 35 individuals (1-69 years) with confirmed ABCC9 variants and their relatives to complete various commonly applied standardized age-related questionnaires, including the Kaufman brief intelligence test 2, the social responsiveness scale-2, and the Achenbach system of empirically based assessment. The majority of CS individuals demonstrated average verbal and nonverbal intelligence compared to the general population. Fifteen percent of cases showed social functioning strongly associated with a clinical diagnosis of autism spectrum disorder. Both externalizing and internalizing problems were also present in this cohort. In particular, anxiety, anxiety or attention deficit hyperactivity disorder, and autism spectrum behaviors were predominantly observed in the younger subjects in the cohort (≥25%), but this percentage decreased markedly in adults.


Assuntos
Comportamento , Cardiomegalia/diagnóstico , Cognição , Hipertricose/diagnóstico , Osteocondrodisplasias/diagnóstico , Fenótipo , Adolescente , Adulto , Idoso , Alelos , Cardiomegalia/genética , Criança , Pré-Escolar , Emoções , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Hipertricose/genética , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Osteocondrodisplasias/genética , Receptores de Sulfonilureias , Adulto Jovem
4.
Biotechnol Prog ; 37(4): e3158, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33891804

RESUMO

Site specific integration (SSI) expression systems offer robust means of generating highly productive and stable cell lines for traditional monoclonal antibodies. As complex modalities such as antibody-like molecules comprised of greater than two peptides become more prevalent, greater emphasis needs to be placed on the ability to produce appreciable quantities of the correct product of interest (POI). The ability to screen several transcript stoichiometries could play a large role in ensuring high amounts of the correct POI. Here we illustrate implementation of an SSI expression system with a single site of integration for development and production of a multi-chain, bi-specific molecule. A SSI vector with a single copy of all of the genes of interest was initially selected for stable Chinese hamster ovary transfection. While the resulting transfection pools generated low levels of the desired heterodimer, utilizing an intensive clone screen strategy, we were able to identify clones having significantly higher levels of POI. In-depth genotypic characterization of clones having the desirable phenotype revealed that a duplication of the light chain within the landing pad was responsible for producing the intended molecule. Retrospective transfection pool analysis using a vector configuration mimicking the transgene configuration found in the clones, as well as other vector configurations, yielded more favorable results with respect to % POI. Overall, the study demonstrated that despite the theoretical static nature of the SSI expression system, enough heterogeneity existed to yield clones having significantly different transgene phenotypes/genotypes and support production of a complex multi-chain molecule.


Assuntos
Cricetulus , Animais , Células CHO , Cricetinae , Proteínas Recombinantes/genética , Estudos Retrospectivos , Transfecção , Transgenes
5.
Am J Med Genet A ; 182(5): 1041-1052, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32100467

RESUMO

Cantú syndrome (CS) was first described in 1982, and is caused by pathogenic variants in ABCC9 and KCNJ8 encoding regulatory and pore forming subunits of ATP-sensitive potassium (KATP ) channels, respectively. It is characterized by congenital hypertrichosis, osteochondrodysplasia, extensive cardiovascular abnormalities and distinctive facial anomalies including a broad nasal bridge, long philtrum, epicanthal folds, and prominent lips. Many genetic syndromes, such as CS, involve facial anomalies that serve as a significant clue in the initial identification of the respective disorder before clinical or molecular diagnosis are undertaken. However, an overwhelming number of CS patients receive misdiagnoses based on an evaluation of coarse facial features. By analyzing three-dimensional images of CS faces, we quantified facial dysmorphology in a cohort of both male and female CS patients with confirmed ABCC9 variants. Morphometric analysis of different regions of the face revealed gender-specific significant differences in face shape. Moreover, we show that 3D facial photographs can distinguish between CS and other genetic disorders with specific facial dysmorphologies that have been mistaken for CS-associated anomalies in the past, hence assisting in an earlier clinical and molecular diagnosis. This optimizes genetic counseling and reduces stress for patients and parents by avoiding unnecessary misdiagnosis.


Assuntos
Cardiomegalia/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Hipertricose/congênito , Canais KATP/genética , Osteocondrodisplasias/genética , Receptores de Sulfonilureias/genética , Adolescente , Adulto , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/fisiopatologia , Criança , Pré-Escolar , Face , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico por imagem , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Predisposição Genética para Doença , Humanos , Hipertricose/diagnóstico por imagem , Hipertricose/genética , Hipertricose/fisiopatologia , Imageamento Tridimensional , Masculino , Mutação de Sentido Incorreto/genética , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/fisiopatologia , Análise de Componente Principal , Adulto Jovem
6.
Am J Med Genet C Semin Med Genet ; 181(4): 658-681, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31828977

RESUMO

Cantú syndrome (CS), first described in 1982, is caused by pathogenic variants in ABCC9 and KCNJ8, which encode the regulatory and pore forming subunits of ATP-sensitive potassium (KATP ) channels, respectively. Multiple case reports of affected individuals have described the various clinical features of CS, but systematic studies are lacking. To define the effects of genetic variants on CS phenotypes and clinical outcomes, we have developed a standardized REDCap-based registry for CS. We report phenotypic features and associated genotypes on 74 CS subjects, with confirmed ABCC9 variants in 72 of the individuals. Hypertrichosis and a characteristic facial appearance are present in all individuals. Polyhydramnios during fetal life, hyperflexibility, edema, patent ductus arteriosus (PDA), cardiomegaly, dilated aortic root, vascular tortuosity of cerebral arteries, and migraine headaches are common features, although even with this large group of subjects, there is incomplete penetrance of CS-associated features, without clear correlation to genotype.


Assuntos
Cardiomegalia/epidemiologia , Hipertricose/epidemiologia , Osteocondrodisplasias/epidemiologia , Sistema de Registros , Adolescente , Adulto , Cardiomegalia/genética , Criança , Fácies , Feminino , Humanos , Hipertricose/genética , Masculino , Osteocondrodisplasias/genética , Fenótipo , Adulto Jovem
7.
J Chem Ecol ; 44(7-8): 637-649, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29956046

RESUMO

We performed single-sensillum recordings from male and female antennae of the Asian longhorned beetle, Anoplophora glabripennis, that included as stimuli the two components of this species' aggregation-sex pheromone in addition to various general odorants. We compared the aggregation-sex-pheromone-component responses of olfactory sensory neurons (OSNs) to those of OSNs that responded to a variety of plant-related odorants. In the smooth-tipped, tapered, trichoid sensilla on the most distal antennal flagellomeres nos. 10 or 11 of both males and females, we found OSNs with high-amplitude action potentials that were tuned to the aldehyde and alcohol pheromone components and that did not respond to various plant-related volatiles. Because this OSN type responded to both the alcohol and aldehyde components it cannot be considered to be specifically tuned to either component. These large-spiking OSNs were co-compartmentalized in these sensilla with a second, smaller-spiking OSN responding to plant-related volatiles such as geraniol, citronellal, limonene, 1-octanol, nerol and citral. The large-spiking OSNs thus appear to be a type that will be involved in aggregation-sex pheromone pathways targeting a specific glomerulus in the antennal lobe and in generating pheromone-related behavioral responses in A. glabripennis. In other sensilla located in these distal antennal flagellomeres as well as those located more proximally, i.e., mid-length along the antenna on flagellomere nos. 4-7, we found OSNs in blunt-tipped basiconic sensilla that were responsive to other plant-related volatiles, especially the terpenoids, (E,E)-alpha farnesene, (E)-ß-farnesene, ß-caryophyllene, and eugenol. Some of these terpenoids have been implicated in improving attraction to pheromone-baited traps. Some of these same OSNs responded additionally to either of the two sex pheromone components, but because these OSNs also responded to some of the above plant volatiles as shown by cross-adaptation experiments, these OSNs will not be the types that convey sex-pheromone-specific information to the antennal lobe.


Assuntos
Besouros/fisiologia , Neurônios Receptores Olfatórios/fisiologia , Sensilas/fisiologia , Atrativos Sexuais/metabolismo , Potenciais de Ação , Animais , Besouros/citologia , Feminino , Masculino , Neurônios Receptores Olfatórios/citologia , Plantas/química , Plantas/metabolismo , Sensilas/citologia , Atrativos Sexuais/química , Comportamento Sexual Animal , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/metabolismo
9.
Environ Microbiol ; 15(7): 2043-62, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23452267

RESUMO

Knowledge of intraspecific variation in symbioses may aid in understanding the ecology of widespread insects in different parts of their range. We investigated bacterial symbionts of Adelges tsugae, a pest of hemlocks in eastern North America introduced from Asia. Amplification, cloning, and sequencing of bacterial 16S rDNA, in situ hybridizations, and electron microscopy revealed that A. tsugae harbours up to five bacterial phylotypes, according to population. Three Gammaproteobacteria species are maternally transmitted. The first, designated 'Ca. Pseudomonas adelgestsugas' resides in the haemocoel, and was detected in all populations except Taiwan. The second phylotype, 'Ca. Serratia symbiotica', resides in bacteriocytes of populations on Tsuga sieboldii in Japan and in E. North America. The third phylotype, designated 'Ca. Annandia adelgestsuga', clustered within a lineage of several insect endosymbionts that included Buchnera aphidicola. It was detected in bacteriocytes in all populations, and in salivary glands of first instars. Two Betaproteobacteria phylotypes were detected in some Japanese T. sieboldii and eastern North America populations, and were observed only in salivary glands with no evidence of maternal transmission. Our results support the ideas that symbiont gain and loss has been volatile in adelgids, and that symbionts may help to trace the source of invasive species.


Assuntos
Biodiversidade , Hemípteros/microbiologia , Espécies Introduzidas , Proteobactérias/classificação , Proteobactérias/genética , Animais , Hibridização in Situ Fluorescente , Japão , Microscopia Confocal , Microscopia Eletrônica de Transmissão , América do Norte , RNA Ribossômico 16S/genética , Simbiose , Taiwan
10.
Nat Biotechnol ; 29(11): 1028-33, 2011 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-22020385

RESUMO

Effective therapies are needed to control excessive bleeding in a range of clinical conditions. We improve hemostasis in vivo using a conformationally pliant variant of coagulation factor Xa (FXa(I16L)) rendered partially inactive by a defect in the transition from zymogen to active protease. Using mouse models of hemophilia, we show that FXa(I16L) has a longer half-life than wild-type FXa and does not cause excessive activation of coagulation. Once clotting mechanisms are activated to produce its cofactor FVa, FXa(I16L) is driven to the protease state and restores hemostasis in hemophilic animals upon vascular injury. Moreover, using human or murine analogs, we show that FXa(I16L) is more efficacious than FVIIa, which is used to treat bleeding in hemophilia inhibitor patients. FXa(I16L) may provide an effective strategy to enhance blood clot formation and act as a rapid pan-hemostatic agent for the treatment of bleeding conditions.


Assuntos
Precursores Enzimáticos/uso terapêutico , Fator Xa/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemostáticos/uso terapêutico , Animais , Coagulação Sanguínea/genética , Modelos Animais de Doenças , Precursores Enzimáticos/farmacocinética , Fator VIIa/genética , Fator VIIa/metabolismo , Fator Xa/farmacocinética , Expressão Gênica , Células HEK293 , Hemorragia/tratamento farmacológico , Hemostasia/genética , Hemostáticos/farmacocinética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Tromboelastografia , Trombina/metabolismo
11.
Shock ; 35(5): 492-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21263385

RESUMO

The RAGE (receptor for advanced glycation end products) is believed to play a role in sepsis by perpetuating inflammation. The interaction of RAGE with a variety of host-derived ligands that accumulate during stress and inflammation further induces the expression of RAGE. It was previously shown that a rat anti-RAGE monoclonal antibody protected mice from lethality in a cecal ligation and puncture model. We studied the effects of a humanized anti-RAGE monoclonal antibody in the murine pneumococcal pneumonia model of sepsis. Moreover, a gene expression analysis was performed in lung tissue of animals that underwent cecal ligation and puncture and treated with the rat anti-RAGE monoclonal antibody, compared with controls. Administration of humanized anti-RAGE mAb 6 h after intratracheal infection with Streptococcus pneumoniae improved mortality in BALB/c mice whether a 7.5 mg/kg (P < 0.01) or a 15 mg/kg dose (P < 0.01) was administered in combination with antibiotics. Gene expression analysis showed that many of the genes modulated by treatment with the anti-RAGE antibody were those that play an important role in regulating inflammation. Anti-RAGE monoclonal antibody offered a survival advantage to septic mice. This protective role in treated animals is supported by the observed gene expression profile changes of genes involved in sepsis and inflammation.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/metabolismo , Receptores Imunológicos/imunologia , Sepse/tratamento farmacológico , Sepse/metabolismo , Animais , Anticorpos Monoclonais/uso terapêutico , Modelos Animais de Doenças , Feminino , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia Pneumocócica/microbiologia , Receptor para Produtos Finais de Glicação Avançada , Sepse/microbiologia , Streptococcus pneumoniae/patogenicidade
12.
J Immunol ; 185(9): 5531-8, 2010 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-20870942

RESUMO

IL-22 is made by a unique set of innate and adaptive immune cells, including the recently identified noncytolytic NK, lymphoid tissue-inducer, Th17, and Th22 cells. The direct effects of IL-22 are restricted to nonhematopoietic cells, its receptor expressed on the surface of only epithelial cells and some fibroblasts in various organs, including parenchymal tissue of the gut, lung, skin, and liver. Despite this cellular restriction on IL-22 activity, we demonstrate that IL-22 induces effects on systemic biochemical, cellular, and physiological parameters. By utilizing adenoviral-mediated delivery of IL-22 and systemic administration of IL-22 protein, we observed that IL-22 modulates factors involved in coagulation, including fibrinogen levels and platelet numbers, and cellular constituents of blood, such as neutrophil and RBC counts. Furthermore, we observed that IL-22 induces thymic atrophy, body weight loss, and renal proximal tubule metabolic activity. These cellular and physiological parameters are indicative of a systemic inflammatory state. We observed that IL-22 induces biochemical changes in the liver including induction of fibrinogen, CXCL1, and serum amyloid A that likely contribute to the reported cellular and physiological effects of IL-22. Based on these findings, we propose that downstream of its expression and impact in local tissue inflammation, circulating IL-22 can further induce changes in systemic physiology that is indicative of an acute-phase response.


Assuntos
Reação de Fase Aguda/imunologia , Reação de Fase Aguda/fisiopatologia , Interleucinas/imunologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Interleucina 22
13.
Rheumatology (Oxford) ; 48(11): 1352-8, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19713442

RESUMO

OBJECTIVES: To investigate the expression and function of triggering receptor expressed on myeloid cells-1 (TREM-1) in the synovium of human RA patients as well as the level of soluble TREM-1 in the plasma of RA patients. METHODS: Twenty-four RA synovial samples were analysed by gene expression oligonucleotide microarrays. Expression levels of TREM-1 mRNA in murine CIA paws were determined by quantitative PCR (qPCR). TREM-1 protein expression was detected by immunohistochemistry in five RA synovial samples and two OA synovial samples. TREM-1-positive cells from five RA synovial tissues were analysed by FACS staining to determine the cell type. Activation of TREM-1 was tested in five RA synovial samples. Soluble TREM-1 was measured in serum from 32 RA patients. RESULTS: The expression of TREM-1 mRNA was found to increase 6.5-fold in RA synovial samples, whereas it was increased 132-fold in CIA paws. Increased numbers of TREM-1-positive cells were seen in RA synovium sections and these cells co-expressed CD14. Using a TREM-1-activating cross-linking antibody in RA synovial cultures, multiple pro-inflammatory cytokines were induced. The average amount of soluble TREM-1 in plasma from RA patients was found to be higher than that in plasma from healthy volunteers. CONCLUSIONS: These findings suggest that the presence of high levels of functionally active TREM-1 in RA synovium may contribute to the development or maintenance of RA, or both. Inhibiting TREM-1 activity may, therefore, have a therapeutic effect on RA. High levels of soluble TREM-1 in the plasma of RA patients compared with healthy volunteers may indicate disease activity.


Assuntos
Artrite Reumatoide/imunologia , Citocinas/biossíntese , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Membrana Sinovial/imunologia , Animais , Artrite Experimental/imunologia , Biomarcadores/metabolismo , Células Cultivadas , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos DBA , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/genética , Receptores Imunológicos/sangue , Receptores Imunológicos/genética , Receptor Gatilho 1 Expresso em Células Mieloides
14.
Environ Entomol ; 38(3): 577-87, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19508766

RESUMO

The hemlock woolly adelgid (Adelges tsugae Annand) is a small, aphid-like insect native to East Asia and western North America. First documented in the eastern United States in Richmond, VA, in 1951, it has spread to at least 17 states, where it causes increased mortality among both eastern and Carolina hemlocks (Tsuga canadensis Carrière and T. caroliniana Engelmann., respectively). Previous work has suggested low temperatures may limit northward spread of the adelgid. Using recent surveys of A. tsugae mortality across the infested latitudinal gradient of the eastern United States, we show there is a significant positive relationship between minimum winter temperatures and winter survival at the landscape scale. The strength and nature of this relationship, however, varies through time, with absolute minimum winter temperatures explaining almost one half of the tree-level variance in survival in the spring of 2004 but only 9% in 2003. Post hoc analyses of the data suggest the explanatory power of temperature can be improved in ongoing studies by examining seasonal temperature profiles. Previous studies have also suggested adelgid survival may be density dependent, and although these data support this observation, contemporary density is a poor predictor of adelgid survival at the landscape scale. Using landscape estimates of minimum winter temperature, we show two simple methods of estimating landscape-scale adelgid survival rates. Both methods suggest much of the range of T. canadensis in the eastern United States, and the entire range of T. caroliniana falls in areas where winter temperatures will not impose critical limits on A. tsugae populations.


Assuntos
Altitude , Temperatura Baixa , Hemípteros/fisiologia , Tsuga , Animais , Modelos Biológicos , Densidade Demográfica , Estações do Ano , Estados Unidos
15.
Atherosclerosis ; 201(1): 53-66, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18377911

RESUMO

OBJECTIVE: The present study was conducted to characterize the expression of the cysteine protease legumain in murine and human atherosclerotic tissues, and to explore the molecular mechanisms by which legumain may contribute to the pathophysiology of atherosclerosis. METHODS AND RESULTS: Using microarray analysis, legumain mRNA expression was found to increase with development of atherosclerosis in the aorta of aging Apolipoprotein E deficient mice while expression remained at low level and unchanged in arteries of age-matched C57BL/6 control mice. In situ hybridization and immunohistochemical analysis determined that legumain was predominantly expressed by macrophages in the atherosclerotic aorta, in lesions at the aortic sinus and in injured carotid arteries of Apolipoprotein E deficient mice as well as in inflamed areas in advanced human coronary atherosclerotic plaques. In vitro, M-CSF differentiated human primary macrophages were shown to express legumain and the protein could also be detected in the culture media. When tested in migration assays, legumain induced chemotaxis of primary human monocytes and human umbilical vein endothelial cells. CONCLUSIONS: Legumain is expressed in both murine and human atherosclerotic lesions. The macrophage-specific expression of legumain in vivo and ability of legumain to induce chemotaxis of monocytes and endothelial cells in vitro suggest that legumain may play a functional role in atherogenesis.


Assuntos
Doenças da Aorta/enzimologia , Doenças da Aorta/etiologia , Aterosclerose/enzimologia , Aterosclerose/etiologia , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Fatores Etários , Animais , Doenças da Aorta/fisiopatologia , Apolipoproteínas E/fisiologia , Aterosclerose/fisiopatologia , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Feminino , Humanos , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/fisiologia , RNA Mensageiro/metabolismo
16.
J Orthop Res ; 26(6): 764-71, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18241059

RESUMO

This study evaluated healing of equine metatarsal osteotomies and ostectomies in response to percutaneous injection of adenoviral (Ad) bone morphogenetic protein (BMP)-2, Ad-BMP-6, or beta-galactosidase protein vector control (Ad-LacZ) administered 14 days after surgery. Radiographic and quantitative computed tomographic assessment of bone formation indicated greater and earlier mineralized callus in both the osteotomies and ostectomies of the metatarsi injected with Ad-BMP-2 or Ad-BMP-6. Peak torque to failure and torsional stiffness were greater in osteotomies treated with Ad-BMP-2 than Ad-BMP-6, and both Ad-BMP-2- and Ad-BMP-6-treated osteotomies were greater than Ad-LacZ or untreated osteotomies. Gene expression of ostectomy mineralized callus 8 weeks after surgery indicated upregulation of genes related to osteogenesis compared to intact metatarsal bone. Expression of transforming growth factor beta-1, cathepsin H, and gelsolin-like capping protein were greater in Ad-BMP-2- and Ad-BMP-6-treated callus compared to Ad-LacZ-treated or untreated callus. Evidence of tissue biodistribution of adenovirus in distant organs was not identified by quantitative PCR, despite increased serum antiadenoviral vector antibody. This study demonstrated a greater relative potency of Ad-BMP-2 over Ad-BMP-6 in accelerating osteotomy healing when administered in this regimen, although both genes were effective at increasing bone at both osteotomy and ostectomy sites.


Assuntos
Proteínas Morfogenéticas Ósseas/genética , Consolidação da Fratura/genética , Fraturas Ósseas/terapia , Terapia Genética/métodos , Osteogênese/genética , Osteotomia , Fator de Crescimento Transformador beta/genética , Adenoviridae/genética , Animais , Fenômenos Biomecânicos , Proteína Morfogenética Óssea 2 , Proteína Morfogenética Óssea 6 , Calo Ósseo/diagnóstico por imagem , Calo Ósseo/fisiopatologia , Modelos Animais de Doenças , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/fisiopatologia , Regulação da Expressão Gênica , Técnicas de Transferência de Genes , Cavalos , Humanos , Óperon Lac , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Tomografia Computadorizada por Raios X , Torque , Torção Mecânica
17.
Mol Med ; 13(1-2): 40-58, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17515956

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. Currently, diagnosis of RA may take several weeks, and factors used to predict a poor prognosis are not always reliable. Gene expression in RA may consist of a unique signature. Gene expression analysis has been applied to synovial tissue to define molecularly distinct forms of RA; however, expression analysis of tissue taken from a synovial joint is invasive and clinically impractical. Recent studies have demonstrated that unique gene expression changes can be identified in peripheral blood mononuclear cells (PBMCs) from patients with cancer, multiple sclerosis, and lupus. To identify RA disease-related genes, we performed a global gene expression analysis. RNA from PBMCs of 9 RA patients and 13 normal volunteers was analyzed on an oligonucleotide array. Compared with normal PBMCs, 330 transcripts were differentially expressed in RA. The differentially regulated genes belong to diverse functional classes and include genes involved in calcium binding, chaperones, cytokines, transcription, translation, signal transduction, extracellular matrix, integral to plasma membrane, integral to intracellular membrane, mitochondrial, ribosomal, structural, enzymes, and proteases. A k-nearest neighbor analysis identified 29 transcripts that were preferentially expressed in RA. Ten genes with increased expression in RA PBMCs compared with controls mapped to a RA susceptibility locus, 6p21.3. These results suggest that analysis of RA PBMCs at the molecular level may provide a set of candidate genes that could yield an easily accessible gene signature to aid in early diagnosis and treatment.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Cromossomos Humanos Par 6/genética , Leucócitos Mononucleares/metabolismo , Adulto , Idoso , Artrite Reumatoide/patologia , Estudos de Casos e Controles , Análise por Conglomerados , Feminino , Fluorescência , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos , RNA/genética , Transcrição Gênica
18.
J Chem Ecol ; 32(11): 2389-403, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17078000

RESUMO

The terpenoid content of eastern hemlock (Tsuga canadensis) foliage was measured over an annual cycle of development from bud opening, shoot elongation, shoot maturation, to bud-break at the start of the next growing season. The objective was to determine if variation in terpenoid composition is linked with spatial and temporal feeding preferences of the hemlock woolly adelgid (HWA; Adelges tsugae). The HWA has two periods of feeding over the course of 1 yr spanning two complete generations. There are two periods of feeding separated by a nonfeeding period where the adelgid estivates. HWA prefers to feed on mature, rather than young, expanding tissue. Feeding occurs in the leaf cushion at the base of the needle. The needle is the only tissue in hemlock with resin canals that store terpenoids. The needle and leaf cushion of both the current and previous years' growth were analyzed separately over a 1-yr period to examine the variation of terpenoid composition in space and time. Terpenoids were quantified by using headspace solid-phase microextraction/gas chromatography/mass spectrometry (SPME/GC/MS). New growth needles and leaf cushions do not resemble the previous year's growth either visually or in chemical composition until October/November, when the adelgid breaks estivation and begins feeding. Nearly all of the 23 terpenoids present exceeding 0.1% varied significantly either temporally or spatially, usually with complex interactions. Ordination and factor analysis revealed that terpenoids are less variable in mature leaf cushions than in young tissue. By entering a nonfeeding diapause during the late spring and summer, HWA avoids the unstable, variable levels of terpenoids in the immature leaf cushion and needles.


Assuntos
Afídeos/fisiologia , Comportamento Alimentar , Terpenos/metabolismo , Tsuga/metabolismo , Animais , Cromatografia Gasosa-Espectrometria de Massas , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Folhas de Planta/parasitologia , Fatores de Tempo , Tsuga/crescimento & desenvolvimento , Tsuga/parasitologia
19.
J Orthop Res ; 24(6): 1279-91, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16649180

RESUMO

Bone marrow-derived mesenchymal stem cells (BMDMSC) hold promise for targeted osteogenic differentiation and can be augmented by delivery of genes encoding bone morphogenetic proteins (BMP). The feasibility of promoting osteogenic differentiation of BMDMSC was investigated using two BMP genes in monolayer and three-dimensional alginate culture systems. Cultured BMDMSC were transduced with E1-deleted adenoviral vectors containing either human BMP2 or BMP6 coding sequence under cytomegalovirus (CMV) promoter control [17:1 multiplicities of infection (moi)] and either sustained in monolayer or suspended in 1 mL 1.2% alginate beads for 22 days. Adenovirus (Ad)-BMP-2 and Ad-BMP-6 transduction resulted in abundant BMP-2 and BMP-6 mRNA and protein expression in monolayer culture and BMP-2 protein expression in alginate cultures. Ad-BMP-2 and Ad-BMP-6 transduced BMDMSC in monolayer had earlier and robust alkaline phosphatase-positive staining and mineralization and were sustained for a longer duration with better morphology scores than untransduced or Ad-beta-galactosidase-transduced cells. Ad-BMP-2- and, to a lesser degree, Ad-BMP-6-transduced BMDMSC suspended in alginate demonstrated greater mineralization than untransduced cells. Gene expression studies at day 2 confirmed an inflammatory response to the gene delivery process with upregulation of interleukin 8 and CXCL2. Upregulation of genes consistent with response to BMP exposure and osteogenic differentiation, specifically endochondral ossification and extracellular matrix proteins, occurred in BMP-transduced cells. These data support that transduction of BMDMSC with Ad-BMP-2 or Ad-BMP-6 can accelerate osteogenic differentiation and mineralization of stem cells in culture, including in three-dimensional culture. BMP-2-transduced stem cells suspended in alginate culture may be a practical carrier system to support bone formation in vivo. BMP-6 induced a less robust cellular response than BMP-2, particularly in alginate culture.


Assuntos
Proteínas Morfogenéticas Ósseas/biossíntese , Células-Tronco Mesenquimais/citologia , Osteogênese/genética , Transdução Genética , Fator de Crescimento Transformador beta/biossíntese , Adenoviridae/genética , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Proteína Morfogenética Óssea 2 , Proteína Morfogenética Óssea 6 , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/farmacologia , Calcificação Fisiológica/efeitos dos fármacos , Calcificação Fisiológica/genética , Diferenciação Celular , Quimiocina CXCL2 , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/farmacologia , Regulação para Cima , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
20.
J Public Health Manag Pract ; 11(5): 407-14, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16103814

RESUMO

San Antonio was selected as an official Mobilizing for Action through Planning and Partnerships (MAPP) demonstration site by National Association of County and City Officials in 2000. The San Antonio Metropolitan Health District, under the leadership of Dr Fernando A. Guerra, agreed to facilitate the process. The MAPP process provided the San Antonio Metropolitan Health District, the local public health authority, a defined process for community health improvement, as well as a mechanism to help bridge the gap between public health and the community. The San Antonio Metropolitan Health District organized a Core Planning Team to lead the MAPP process in April 2001. By October 2002, the Core Planning Team was expanded to a full community working group named the Alliance for Community Health in San Antonio and Bexar County (Alliance). The Alliance identified six strategic issues, which eventually became the basis of the San Antonio Community Health Improvement Plan. The strategic issues are Public Policy, Data Tracking, Healthy Lifestyles, Promoting a Sense of Community, Access to Care, and Safe Environment. San Antonio's MAPP experience has been successful in bringing together the public health system partners, and establishing public health priorities collectively. The MAPP process has resulted in the development of many new initiatives, and, most important, has opened the door to many partnership opportunities in the future. The work of the Alliance, through the MAPP process, has helped to leverage resources for public health improvement in San Antonio, and has the potential to effect positive change in public health in the future.


Assuntos
Planejamento em Saúde Comunitária/organização & administração , Planejamento em Saúde Comunitária/métodos , Avaliação de Programas e Projetos de Saúde , Prática de Saúde Pública , Texas
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