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1.
Diabetes Spectr ; 31(4): 310-319, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30510385

RESUMO

IN BRIEF In 2017, 30 million Americans had diabetes, and 84 million had prediabetes. In this article, the authors focus on the journey people at risk for type 2 diabetes take when they become fully engaged in an evidence-based type 2 diabetes prevention program. They highlight potential drop-off points along the journey, using behavioral economics theory to provide possible reasons for most of the drop-off points, and propose solutions to move people toward making healthy decisions.

2.
J Asthma ; 53(2): 133-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26308287

RESUMO

BACKGROUND: Dust mite allergens can induce allergic sensitization and exacerbate asthma symptoms. Although dust mite reduction and control strategies exist, few asthmatics employ them. OBJECTIVES: We examined whether an in-home test kit, which quantifies dust mite allergen levels, resulted in behavioral changes in implementation and maintenance of mite reduction strategies and helped reduce allergen levels in homes of dust mite-sensitive children. METHODS: We enrolled 60 households of children aged 5-15 with parent-reported dust mite allergy into a randomized controlled trial. Intervention homes (N = 30) received educational material about reducing dust mites and test kits at 1, 2, 5 and 8 months. Control homes (N = 30) received only educational material. At baseline, 6 and 12 months, study staff visited all homes, collected dust samples from three locations and obtained information about parents' mite reduction behaviors by questionnaire. Allergen concentrations (Der f 2/Der p2) in dust were assessed by immunoassays. After adjusting for visit and location, allergen concentrations in intervention and control homes were compared using mixed effects model analysis. RESULTS: In the intervention homes, allergen concentrations in the child's bedroom and living room floors were significantly reduced over time compared to control homes. Although not all location-specific differences in allergen concentrations were statistically significant, combining data across locations, there was a differential reduction in allergen concentrations in the intervention group versus the control group (p = 0.02). CONCLUSION: The use of in-home test kits along with education may beneficially influence behaviors and attitudes toward dust mite reduction strategies and help reduce residential dust mite allergen levels.


Assuntos
Poluição do Ar em Ambientes Fechados/prevenção & controle , Alérgenos/análise , Antígenos de Dermatophagoides/análise , Proteínas de Artrópodes/análise , Cisteína Endopeptidases/análise , Poeira/análise , Monitoramento Ambiental/instrumentação , Adolescente , Poluição do Ar em Ambientes Fechados/análise , Criança , Pré-Escolar , Educação em Saúde , Habitação , Humanos , Projetos Piloto
3.
Proc Natl Acad Sci U S A ; 107(22): 10280-4, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20479243

RESUMO

Although multiple follicles are present in mammalian ovaries, most of them remain dormant for years or decades. During reproductive life, some follicles are activated for development. Genetically modified mouse models with oocyte-specific deletion of genes in the PTEN-PI3K-Akt-Foxo3 pathway exhibited premature activation of all dormant follicles. Using an inhibitor of the Phosphatase with TENsin homology deleted in chromosome 10 (PTEN) phosphatase and a PI3K activating peptide, we found that short-term treatment of neonatal mouse ovaries increased nuclear exclusion of Foxo3 in primordial oocytes. After transplantation under kidney capsules of ovariectomized hosts, treated follicles developed to the preovulatory stage with mature eggs displaying normal epigenetic changes of imprinted genes. After in vitro fertilization and embryo transfer, healthy progeny with proven fertility were delivered. Human ovarian cortical fragments from cancer patients were also treated with the PTEN inhibitor. After xeno-transplantation to immune-deficient mice for 6 months, primordial follicles developed to the preovulatory stage with oocytes capable of undergoing nuclear maturation. Major differences between male and female mammals are unlimited number of sperm and paucity of mature oocytes. Thus, short-term in vitro activation of dormant ovarian follicles after stimulation of the PI3K-Akt pathway allows the generation of a large supply of mature female germ cells for future treatment of infertile women with a diminishing ovarian reserve and for cancer patients with cryo-preserved ovaries. Generation of a large number of human oocytes also facilitates future derivation of embryonic stem cells for regenerative medicine.


Assuntos
Oócitos/fisiologia , Folículo Ovariano/citologia , Folículo Ovariano/fisiologia , Animais , Animais Recém-Nascidos , Transferência Embrionária , Feminino , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/metabolismo , Humanos , Técnicas In Vitro , Masculino , Camundongos , Oócitos/citologia , Oócitos/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Folículo Ovariano/efeitos dos fármacos , Ovário/transplante , PTEN Fosfo-Hidrolase/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transplante Heterólogo
4.
Biol Reprod ; 84(4): 707-14, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21178173

RESUMO

Development of ovarian follicles is regulated by pituitary-derived gonadotropins together with local ovarian paracrine factors. Based on DNA microarray data, we performed RT-PCR and immunostaining to demonstrate the expression of interleukin 7 transcripts in oocytes of preantral, antral, and preovulatory follicles in rats. We also found the expression of interleukin 7 receptor and the coreceptor interleukin 2 receptor gamma in granulosa cells, cumulus cells, and preovulatory oocytes. In cultured rat granulosa cells obtained from early antral and preovulatory follicles, treatment with interleukin 7 stimulated the phosphorylation of AKT, glycogen synthase kinase (GSK3B), and STAT5 proteins in a time- and dose-dependent manner. Furthermore, measurement of mitochondrial reductase activity indicated that treatment with interleukin 7, similar to gonadotropins, increased the number of viable granulosa cells during a 24-h culture period. Furthermore, monitoring of the activities of apoptotic enzymes (caspase 3/7) indicated that treatment with interleukin 7 suppressed apoptosis of cultured granulosa cells from both antral and preovulatory follicles following serum withdrawal. The apoptosis-suppressing actions of interleukin 7 were blocked by an inhibitor of the phosphoinositol-3-kinase (PIK3)/AKT pathway. Furthermore, treatment of cultured preovulatory follicles with interleukin 7, like treatment with human chorionic gonadotropin, induced germinal vesicle breakdown of oocytes. The stimulatory effect of interleukin 7 was also blocked by inhibitors of the PIK3/AKT pathway. The present findings suggest that oocyte-derived interleukin 7 could act on neighboring granulosa cells as a survival factor and promote the nuclear maturation of preovulatory oocytes through activation of the PIK3/AKT pathway.


Assuntos
Células da Granulosa/citologia , Células da Granulosa/fisiologia , Interleucina-7/genética , Interleucina-7/fisiologia , Oócitos/crescimento & desenvolvimento , Oócitos/fisiologia , Animais , Apoptose/efeitos dos fármacos , Sequência de Bases , Células Cultivadas , Primers do DNA/genética , Feminino , Expressão Gênica , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Células da Granulosa/efeitos dos fármacos , Subunidade gama Comum de Receptores de Interleucina/genética , Interleucina-7/farmacologia , Oócitos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-7/genética , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais
5.
Mol Endocrinol ; 22(6): 1464-75, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18337590

RESUMO

Obestatin was identified as a brain/gut peptide hormone encoded by the ghrelin gene and found to interact with the G protein-coupled receptor, GPR39. We investigated target cells for obestatin based on induction of an early-response gene c-fos in different tissues. After ip injection of obestatin, c-fos staining was found in the nuclei of gastric mucosa, intestinal villi, white adipose tissues, hepatic cords, and kidney tubules. Immunohistochemical analyses using GPR39 antibodies further revealed cytoplasmic staining in these tissues. In cultured 3T3-L1 cells, treatment with obestatin, but not motilin, induced c-fos expression. In these preadipocytes, treatment with obestatin also stimulated ERK1/2 phosphorylation. Because phenotypes of GPR39 null mice are partially consistent with a role of GPR39 in mediating obestatin actions, we hypothesized that inconsistencies on the binding of iodinated obestatin to GPR39 are due to variations in the bioactivity of iodinated obestatin. We obtained monoiodoobestatin after HPLC purification and demonstrated its binding to jejunum, stomach, ileum, pituitary, and white adipose tissue. Furthermore, human embryonic kidney 293T cells transfected with plasmids encoding human or mouse GPR39 or a human GPR39 isoform, but not the ghrelin receptor, exhibited high-affinity binding to monoiodoobestatin. Binding studies using jejunum homogenates and recombinant GPR39 revealed obestatin-specific displacement curves. Furthermore, treatment with obestatin induced c-fos expression in gastric mucosa of wild-type, but not GPR39 null, mice, underscoring a mediating role of this receptor in obestatin actions. The present findings indicate that obestatin is a metabolic hormone capable of binding to GPR39 to regulate the functions of diverse gastrointestinal and adipose tissues.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Grelina/farmacologia , Receptores Acoplados a Proteínas G/fisiologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Células Cultivadas , Feminino , Trato Gastrointestinal/metabolismo , Genes fos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Fatores de Tempo , Transcrição Gênica/efeitos dos fármacos
6.
Am J Ind Med ; 52(2): 99-104, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19016305

RESUMO

BACKGROUND: Home care/hospice nurses may be at elevated risk of blood exposure because of the nature of their work and work environment. However, little is known about the incidence of blood exposure in this population. METHODS: A mail survey (n = 1,473) was conducted among home care/hospice nurses in North Carolina in 2006. RESULTS: The adjusted response rate was 69%. Nine percent of nurses had at least one exposure/year. Overall incidence was 27.4 (95% confidence interval: 20.2, 34.6)/100,000 visits. Nurses who had worked in home care < or =5 years had higher exposure rates than other nurses-seven times higher for needlesticks and 3.5 times higher for non-intact skin exposures. Nurses who worked part time/contract had higher exposure rates than nurses who worked full time-seven times higher for needlesticks and 1.5 times higher for non-intact skin exposures. The rates for part-time/contract nurses with < or =5 years experience were extremely high. Sensitivity analysis showed that it is unlikely that response bias had an important impact on these results. CONCLUSIONS: Approximately 150 North Carolina home care/hospice nurses are exposed to blood annually. If these results are representative of other states, then approximately 12,000 home care/hospice nurses are exposed each year nationwide. Improved prevention efforts are needed to reduce blood exposure in home care/hospice nurses. Am. J. Ind. Med. 52:99-104, 2009. (c) 2008 Wiley-Liss, Inc.


Assuntos
Patógenos Transmitidos pelo Sangue , Assistência Domiciliar/estatística & dados numéricos , Cuidados Paliativos na Terminalidade da Vida/estatística & dados numéricos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Exposição Ocupacional/efeitos adversos , Adulto , Feminino , Humanos , Incidência , Transmissão de Doença Infecciosa do Paciente para o Profissional/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Fatores de Risco , Sensibilidade e Especificidade , Inquéritos e Questionários , Local de Trabalho/estatística & dados numéricos
7.
Mol Endocrinol ; 20(10): 2528-38, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16762976

RESUMO

In addition to gonadotropins, many ovarian paracrine factors are crucial for optimal follicle rupture, oocyte maturation, and luteinization. Based on DNA microarray analyses, we found that transcripts for the fibroblast growth factor-inducible-14 (Fn14) receptor are increased after LH/human chorionic gonadotropin (hCG) treatment of gonadotropin-primed immature mice or rats. Fn14 is the cognate receptor for TNF-related weak inducer of apoptosis (TWEAK), a TNF superfamily member. TWEAK transcripts also were detected in the ovary; however, their levels were not regulated by gonadotropins. In situ hybridization analyses indicated that the Fn14 receptor is expressed in the granulosa and cumulus cells of preovulatory follicles and, to a lesser extent, in theca cells. In contrast, in situ hybridization analyses revealed that TWEAK is primarily expressed in theca cells. In cultured granulosa cells pretreated with hCG to induce Fn14 receptor expression, treatment with TWEAK suppressed progesterone synthesis without accompanying changes in cAMP production. Furthermore, intrabursal injection of TWEAK suppressed ovarian progesterone content in gonadotropin-primed rats. In contrast, preovulatory follicles cultured in the presence of the Fn14 decoy, a recombinant protein containing the ligand-binding domain of Fn14, led to increases in progesterone production, presumably by antagonizing the actions of endogenous TWEAK. Likewise, ip injection of the Fn14 decoy enhanced serum progesterone levels with accompanying increases in transcript levels for several key steroidogenic enzymes. The present findings demonstrate a suppressive role of the TWEAK/Fn14 signaling system in the ovary. Following gonadotropin induction of ovulation, Fn14 is induced and could protect preovulatory follicles from excessive luteinization.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Luteinização/metabolismo , Folículo Ovariano/metabolismo , Ovário/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Fatores de Necrose Tumoral/metabolismo , Animais , Western Blotting , Gonadotropina Coriônica/farmacologia , Citocina TWEAK , Primers do DNA , Feminino , Hibridização In Situ , Análise em Microsséries , Folículo Ovariano/fisiologia , Progesterona/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Necrose Tumoral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor de TWEAK , Células Tecais/metabolismo , Fatores de Necrose Tumoral/genética
8.
J Assoc Nurses AIDS Care ; 28(4): 491-503, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28442187

RESUMO

Engaging and retaining persons with HIV in care and treatment is key to reducing new HIV infections in the United States. Understanding the experiences, barriers, and facilitators to engaging and retaining persons in HIV care from the perspective of HIV care providers could help provide insight into how best to achieve this goal. We present qualitative data from 30 HIV care providers in three cities. We identified three facilitators to HIV care: providing a medical home, team-based care and strategies for engaging and retaining patients in HIV care, and focus on provider-patient relationships. We identified two main barriers to care: facility-level policies and patient-level challenges. Our findings suggest that providers embrace the medical home model for engaging patients but need support to identify aspects of the model that promote engagement in long-term HIV care, improve the quality of the provider-patient relationship, and address persistent logistical barriers, such as transportation.


Assuntos
Continuidade da Assistência ao Paciente , Infecções por HIV/epidemiologia , Pessoal de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Assistência Centrada no Paciente , Relações Profissional-Paciente , Adulto , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Acessibilidade aos Serviços de Saúde , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Pesquisa Qualitativa , Estigma Social , Apoio Social
9.
Contraception ; 73(1): 65-71, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16371298

RESUMO

BACKGROUND: Assessing the psychological acceptability of technologies designed to assist couples in achieving pregnancy is complex. OBJECTIVE: The current study developed measures relating to the impact of one such technology on 52 couples' relationships, their feelings relating to pregnancy status and their feelings about the technology itself. METHODS: Pregnancy status and daily logs of sexual activity were recorded for four menstrual cycles, in addition to the completion of acceptability questionnaires. RESULTS: Baseline acceptability measures were more favorable among couples eventually achieving pregnancy. For couples not becoming pregnant, acceptability declined over time and relationships became more strained. Behavioral data clearly indicated a "targeting" and focusing of sexual activity in response to the information displayed by the monitor. CONCLUSION: Expectations of success, couple disagreements about prior failure and partner communication patterns appear to be related to pregnancy success when using such technology.


Assuntos
Infertilidade/terapia , Detecção da Ovulação/instrumentação , Detecção da Ovulação/psicologia , Adulto , Coito , Emoções , Feminino , Humanos , Relações Interpessoais , Masculino , Ciclo Menstrual , Pessoa de Meia-Idade , Satisfação do Paciente , Gravidez , Inquéritos e Questionários
10.
Mol Endocrinol ; 19(11): 2824-38, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16002435

RESUMO

Calcitonin, alpha- and beta-calcitonin gene-related peptides, amylin, and adrenomedullin belong to a unique group of peptide hormones important for homeostasis maintenance. We recently identified intermedin (IMD) as a novel member of the calcitonin/calcitonin gene-related peptide family expressed in the pituitary, digestive tract, and other organs of vertebrates. Real-time PCR and immunohistochemical analysis of pituitaries from rats at different stages of development showed that IMD is expressed in the intermediate lobe and select adrenocorticotrophs in the anterior lobe, suggesting that IMD could function as a paracrine factor regulating anterior pituitary hormone secretion. In support of a paracrine role for IMD in the pituitary, quantitative and in situ hybridization analyses showed the expression of IMD receptor transcripts including the calcitonin receptor-like receptor and receptor activity-modifying proteins in the pituitary. Treatment with IMD leads to a dose-dependent increase of prolactin release in cultured rat pituitary cells. In contrast, IMD treatment has negligible effects on the release of GH, FSH, or ACTH. Likewise, in vivo treatment with IMD leads to an elevation of plasma prolactin levels in conscious rats. Based on these functional characteristics, we hypothesized that IMD could represent one of the intermediate lobe-derived prolactin-releasing factors important for prolactin regulation during reproduction. In support of this hypothesis, studies of IMD expression in lactating and ovariectomized rats showed that pituitary IMD transcripts in lactating animals increased to more than 2-fold over nonlactating controls whereas ovariectomy leads to a 90% reduction of IMD expression in the pituitary. Of importance, subsequent treatment with 17beta-estradiol or diethylstilbestrol increased pituitary IMD expression in ovariectomized rats. In addition, analysis of the proximate region of the IMD gene promoter showed that the IMD gene promoter contains consensus estrogen response element sequences, and estrogen treatments up-regulate the promoter reporter activity in transfected pituitary cells. Collectively, the present study indicates that IMD represents a novel estrogen-dependent intermediate lobe-derived prolactin-releasing factor and could play important roles in the regulation of prolactin release during reproduction in females.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Neuropeptídeos/fisiologia , Adeno-Hipófise/metabolismo , Prolactina/metabolismo , Hormônio Adrenocorticotrópico/análise , Hormônio Adrenocorticotrópico/metabolismo , Adrenomedulina , Sequência de Aminoácidos , Animais , Proteína Semelhante a Receptor de Calcitonina , Células Cultivadas , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lactação/metabolismo , Proteínas de Membrana/genética , Dados de Sequência Molecular , Neuropeptídeos/análise , Neuropeptídeos/genética , Comunicação Parácrina , Adeno-Hipófise/química , Adeno-Hipófise/crescimento & desenvolvimento , Transporte Proteico , Ratos , Proteínas Modificadoras da Atividade de Receptores , Receptores da Calcitonina/genética , Transcrição Gênica
11.
Mol Endocrinol ; 18(8): 2085-96, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15131261

RESUMO

Stanniocalcin (STC) in fish maintains calcium and phosphate homeostasis, whereas mammalian STC1 shows a diverse tissue expression pattern with ovary exhibiting the highest level. Based on the known expression of STC1 in theca/interstitial cells of the ovary, we generated recombinant N-glycosylated STC1 protein and tested its ability to modulate granulosa cell differentiation. In cultured rat granulosa cells obtained from early antral follicles, treatment with STC1 suppressed FSH-stimulated progesterone biosynthesis with minimal effects on estradiol and cAMP production. In mature granulosa cells, treatment with STC1 also suppressed human chorionic gonadotropin-induced progesterone production. The inhibitory effect of STC1 was accompanied by a pronounced suppression of the CYP11A transcripts and the FSH induction of functional LH receptors. In addition, STC1 was found to act downstream of adenyl cyclases in suppressing progesterone biosynthesis. We also tested the regulation of STC1 gene expression by gonadotropins. Treatment with pregnant mare serum gonadotropin decreased STC1 transcript levels in theca cells of maturing follicles, whereas subsequent treatment with human chorionic gonadotropin led to sustained suppression in the corpora lutea. Using radiolabeled recombinant STC1, receptor assays showed specific STC1 binding with a high affinity to granulosa cells. Because STC1 is expressed in ovarian theca/interstitial cells, the present demonstration of receptor binding and the specific actions of STC1 in granulosa cells suggest the existence of a follicular paracrine system in which theca cell-derived STC1 dampens the gonadotropin stimulation of granulosa cell differentiation. The observed STC1 suppression of progesterone, but not estradiol, production further suggests the potential role of this paracrine hormone as a luteinization inhibitor.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Glicoproteínas/farmacologia , Células da Granulosa/efeitos dos fármacos , Comunicação Parácrina/efeitos dos fármacos , Receptores de Superfície Celular/metabolismo , Animais , Células Cultivadas , Gonadotropina Coriônica/farmacologia , AMP Cíclico/biossíntese , AMP Cíclico/metabolismo , Estradiol/metabolismo , Feminino , Hormônio Foliculoestimulante/biossíntese , Hormônio Foliculoestimulante/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas/genética , Glicoproteínas/isolamento & purificação , Células da Granulosa/citologia , Células da Granulosa/metabolismo , Humanos , Progesterona/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores do LH/metabolismo
12.
Mol Endocrinol ; 18(3): 653-65, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14684852

RESUMO

Growth differentiation factor-9 (GDF-9) is an oocyte-derived growth factor and a member of the TGF-beta superfamily that includes TGF-beta, activin, and bone morphogenetic proteins (BMPs). GDF-9 is indispensable for the development of ovarian follicles from the primary stage, and treatment with GDF-9 enhances the progression of early follicles into small preantral follicles. Similar to other TGF-beta family ligands, GDF-9 likely initiates signaling mediated by type I and type II receptors with serine/threonine kinase activity, followed by the phosphorylation of intracellular transcription factors named Smads. We have shown previously that GDF-9 interacts with the BMP type II receptor (BMPRII) in granulosa cells, but the type I receptor involved is unknown. Using P19 cells, we now report that GDF-9 treatment stimulated the CAGA-luciferase reporter known to be responsive to TGF-beta mediated by the type I receptor, activin receptor-like kinase (ALK)5. In contrast, GDF-9 did not stimulate BMP-responsive reporters. In addition, treatment with GDF-9 induced the phosphorylation of Smad2 and Smad3 in P19 cells, and the stimulatory effect of GDF-9 on the CAGA-luciferase reporter was blocked by the inhibitory Smad7, but not Smad6. We further reconstructed the GDF-9 signaling pathway using Cos7 cells that are not responsive to GDF-9. After overexpression of ALK5, with or without exogenous Smad3, the Cos7 cells gained GDF-9 responsiveness based on the CAGA-luciferase reporter assay. The roles of ALK5 and downstream pathway genes in mediating GDF-9 actions were further tested in ovarian cells. In cultured rat granulosa cells from early antral follicles, treatment with GDF-9 stimulated the CAGA-luciferase reporter activity and induced the phosphorylation of Smad3. Furthermore, transfection with small interfering RNA for ALK5 or overexpression of the inhibitory Smad7 resulted in dose-dependent suppression of GDF-9 actions. In conclusion, although GDF-9 binds to the BMP-activated type II receptor, its downstream actions are mediated by the type I receptor, ALK5, and the Smad2 and Smad3 proteins. Because ALK5 is a known receptor for TGF-beta, diverse members of the TGF-beta family of ligands appear to interact with a limited number of receptors in a combinatorial manner to activate two downstream Smad pathways.


Assuntos
Receptores de Ativinas Tipo I/metabolismo , Receptores de Ativinas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteína Smad2 , Receptores de Ativinas/efeitos dos fármacos , Receptores de Ativinas/genética , Receptores de Ativinas Tipo I/efeitos dos fármacos , Receptores de Ativinas Tipo I/genética , Ativinas/metabolismo , Ativinas/farmacologia , Animais , Proteína Morfogenética Óssea 15 , Proteínas Morfogenéticas Ósseas/metabolismo , Células COS/efeitos dos fármacos , Células COS/metabolismo , Células Cultivadas , Proteínas de Ligação a DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Fator 9 de Diferenciação de Crescimento , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Fosforilação , Regiões Promotoras Genéticas , Proteínas Serina-Treonina Quinases , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/efeitos dos fármacos , Receptores de Fatores de Crescimento Transformadores beta/genética , Transdução de Sinais , Proteínas Smad , Proteína Smad3 , Proteína Smad6 , Proteína Smad7 , Transativadores/efeitos dos fármacos , Transativadores/genética , Transativadores/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia
13.
Mol Endocrinol ; 18(9): 2241-54, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15192078

RESUMO

Leucine-rich repeat-containing, G protein-coupled receptors (LGRs) belong to the largest mammalian superfamily of proteins with seven-transmembrane domains. LGRs can be divided into three subgroups based on their unique domain arrangement. Although two subgroups have been found to be receptors for glycoprotein hormones and relaxin-related ligands, respectively, the third LGR subgroup, consisting of LGR4-6, are orphan receptors with unknown physiological roles. To elucidate the functions of this subgroup of LGRs, LGR4 null mice were generated using a secretory trap approach to delete the majority of the LGR4 gene after the insertion of a beta-galactosidase reporter gene immediately after exon 1. Tissues expressing LGR4 were analyzed based on histochemical staining of the transgene driven by the endogenous LGR4 promoter. LGR4 was widely expressed in kidney, adrenal gland, stomach, intestine, heart, bone/cartilage, and other tissues. The expression of LGR4 in these tissues was further confirmed by immunohistochemical studies in wild-type animals. Analysis of the viability of 250 newborn animals suggested a skewed inheritance pattern, indicating that only 40% of the expected LGR4 null mice were born. For the LGR4 null mice viable at birth, most of them died within 2 d. Furthermore, the LGR4 null mice showed intrauterine growth retardation as reflected by a 14% decrease in body weight at birth, together with 30% and 40% decreases in kidney and liver weights, respectively. The present findings demonstrate the widespread expression of LGR4, and an essential role of LGR4 for embryonic growth, as well as kidney and liver development. The observed pre- and postnatal lethality of LGR4 null mice illustrates the importance of the LGR4 signaling system for the survival and growth of animals during the perinatal stage.


Assuntos
Retardo do Crescimento Fetal/etiologia , Leucina/genética , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/fisiologia , Sequência de Aminoácidos , Animais , Células Epiteliais/imunologia , Feminino , Expressão Gênica/genética , Genes Letais , Genes Reporter/genética , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Rim/citologia , Rim/imunologia , Rim/metabolismo , Leucina/análise , Fígado/imunologia , Fígado/metabolismo , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Mutagênese Insercional/genética , Gravidez , Regiões Promotoras Genéticas/genética , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Receptor IGF Tipo 1/genética , Receptores Acoplados a Proteínas G/análise , Sequências Repetitivas de Aminoácidos , Distribuição Tecidual , beta-Galactosidase/análise , beta-Galactosidase/genética
14.
Pers Soc Psychol Bull ; 31(2): 267-75, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15619598

RESUMO

Research shows that people display a downward shift in their predictions in anticipation of performance and feedback. The authors used a misattribution paradigm to explore whether anxiety serves as a signal for predictions. Participants (N = 108) anticipating results from an important test either immediately or in a few days were or were not encouraged to attribute any arousal they experienced to coffee they consumed earlier. Consistent with predictions, participants encouraged to attribute their arousal to the coffee were optimistic in their predictions even when anticipating immediate test feedback. In addition, the more participants attributed their arousal to the coffee, the more optimistic they were in their predictions. Ancillary analyses suggest that anxiety can be a cause rather than a consequence of less optimistic predictions.


Assuntos
Ansiedade , Nível de Alerta , Atitude , Retroalimentação Psicológica , Logro , Adulto , Feminino , Previsões , Humanos , Masculino , Distribuição Aleatória , Assunção de Riscos , Análise e Desempenho de Tarefas
15.
Endocrinology ; 145(7): 3424-33, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15059956

RESUMO

Premature ovarian failure in a subgroup of women with blepharophimosis-ptosis-epicanthus inversus type 1 syndrome has been associated with nonsense mutations in the gene encoding a Forkhead transcription factor, Forkhead L2 (FOXL2). However, the exact function of FOXL2 in the ovary is unclear. We investigated the expression of FOXL2 in the mouse ovary during follicular development and maturation by RT-PCR and in situ hybridization. The FOXL2 mRNA is expressed in ovaries throughout development and adulthood and is localized to the undifferentiated granulosa cells in small and medium follicles as well as cumulus cells of preovulatory follicles. FOXL2 belongs to a group of transcription factors capable of interacting with specific DNA sequences in diverse gene promoters. With the presence of multiple putative forkhead DNA consensus sites, the promoter of the human steroidogenic acute regulatory (StAR) gene was used to test for regulation by FOXL2. Cotransfection studies revealed that wild-type FOXL2 represses the activity of the StAR promoter, and the first 95 bp upstream of the transcriptional start site of the StAR gene is sufficient for FOXL2 repression. EMSAs confirmed that FOXL2 interacts directly with this region. Analyses using FOXL2 mutants also demonstrated the importance of the entire alanine/proline-rich carboxyl terminus of FOXL2 for transcriptional repression. Furthermore, these mutations produce a protein with a dominant-negative effect that disables the transcriptional repressor activity of wild-type FOXL2. Dominant-negative mutations of FOXL2 could increase expression of StAR and other follicle differentiation genes in small and medium follicles to accelerate follicle development, resulting in increased initial recruitment of dormant follicles and thus the premature ovarian failure phenotype.


Assuntos
Proteínas de Ligação a DNA/genética , Ovário/embriologia , Ovário/fisiologia , Fosfoproteínas/genética , Insuficiência Ovariana Primária/fisiopatologia , Fatores de Transcrição/genética , Alanina/metabolismo , Animais , Animais não Endogâmicos , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Feminino , Proteína Forkhead Box L2 , Fatores de Transcrição Forkhead , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Mutagênese , Peptídeos/genética , Peptídeos/metabolismo , Fenótipo , Gravidez , Domínios Proteicos Ricos em Prolina , Regiões Promotoras Genéticas , Estrutura Terciária de Proteína , RNA Mensageiro/análise , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Transcrição Gênica/fisiologia
16.
Health Psychol ; 22(2): 166-77, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12683737

RESUMO

This meta-analysis examined the validity of various theoretical assumptions about cognitive and behavioral change following a communication recommending condom use. The synthesis comprised 82 treatment and 29 control groups included in 46 longitudinal reports with measures of perceived severity and susceptibility, attitudes and expectancies, norms, perceptions of control, intentions, knowledge, behavioral skills, or condom use. Results indicated that across the sample of studies, communications taught recipients about facts related to HIV and also induced favorable attitudes and expectancies, greater control perceptions, and stronger intentions to use condoms in the future. Moreover, messages that presented attitudinal information and modeled behavioral skills led to increased condom use. Results are discussed in the context of theories of human behavior and change and in reference to HIV-prevention interventions.


Assuntos
Síndrome da Imunodeficiência Adquirida/prevenção & controle , Cognição , Soropositividade para HIV/transmissão , Comportamentos Relacionados com a Saúde , Educação em Saúde , Comunicação Persuasiva , Seguimentos , Humanos , Comportamento Sexual
17.
J Soc Psychol ; 142(1): 87-96, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11915857

RESUMO

A new contraceptive technology may advance the science of family planning but may do little to affect health if potential users do not deem it an acceptable method. The authors conducted an acceptability study of a newly developed contraceptive method--personal hormone monitoring. A sample of 480 English volunteers present at the 6th month of a 13-month longitudinal study completed surveys regarding their attitudes toward a personal hormone monitor for the purpose of contraception. The authors used the participants' responses to determine (a) the extent to which the participants accepted the monitor, (b) how their ratings of acceptability changed over time, (c) the extent to which contextual variables predicted changes in acceptability over time, and (d) whether those contextual variables predicted final acceptability of the monitor. Results suggested that no single method of family planning is best for everyone and specified the people for whom personal hormone monitoring may be most suitable.


Assuntos
Atitude Frente a Saúde , Comportamento Contraceptivo , Serviços de Planejamento Familiar , Mulheres/psicologia , Adulto , Comportamento do Consumidor , Anticoncepcionais Femininos , Inglaterra , Serviços de Planejamento Familiar/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores Sexuais , Inquéritos e Questionários , Fatores de Tempo
18.
Patient Prefer Adherence ; 7: 15-20, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23319854

RESUMO

BACKGROUND: Stem cell transplant (SCT) is a treatment choice for many hematological malignancies. There is currently a lack of evidence regarding the self-reported concerns of SCT patients before and after SCT. AIM AND DESIGN: This exploratory study performed a secondary analysis of self-reported, written concerns of SCT patients before and after transplant to determine patients' concerns. METHODS: Content analysis of text box entries of SCT patients collected between 2005 and 2007 at the Seattle Cancer Care Alliance. Text box entries were collected as part of symptom assessment using the Electronic Self-Report Assessment - Cancer instrument. The assessment was presented to 137 patients undergoing SCT at two time points: prior to ambulatory visits before any therapy had begun (T1) and at the first visit after hospital discharge following SCT (T2). RESULTS: Text box entries were made before (n = 52) and after (n = 87) the transplant, resulting in 139 text box entries made by 137 patients representing 133 concerns. Using content analysis, the entries were categorized and ranked according to frequency. After symptom concerns, patients ranked work and financial issues the most frequent concerns prior to SCT. After SCT, symptoms remained the most frequently entered area of concern, followed by survival. CONCLUSION: Oncology providers need to assess SCT patients for work and financial concerns before and after transplant. Appropriate and timely referrals may ease the burden of these concerns for patients. Thus, assessment of financial and work concerns by the oncology team should be an integral part of quality health care for patients undergoing SCT.

19.
Epidemiol Health ; 33: e2011008, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21977337

RESUMO

OBJECTIVES: Formative research can serve as a means of obtaining important information for designing an epidemiologic study, but descriptions of this approach in the epidemiologic literature are lacking. The objective of this paper is to describe the use of three formative research techniques in designing a survey of home care and hospice nurses. METHODS: We conducted two focus groups, seven key informant interviews, and approximately fifteen hours of direct observation among home care and hospice nurses recruited by word of mouth in North Carolina in 2006. RESULTS: We used information obtained from the formative research to decide which survey design would likely be most successful with this population (mail survey, as opposed to Internet survey or in-person interviews), which measure to use for the denominator of the blood exposure incidence rates (number of visits, as opposed to patient-time), and which items and response options to include in the questionnaire, as well as to identify specific survey techniques that would likely increase the response rate (emphasizing the regional focus of the study; sending the questionnaire to the home address). CONCLUSION: When particular information for planning a study is unavailable from the literature or the investigator's experience, formative research can be an effective means of obtaining that information.

20.
J Sch Health ; 80(3): 112-8, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20236412

RESUMO

BACKGROUND: To reduce the number of sports-related concussions, the Centers for Disease Control and Prevention (CDC), with the support of partners and experts in the field, has developed a tool kit for high school coaches with practical, easy-to-use concussion-related information. This study explores the success of the tool kit in changing knowledge, attitudes, and practices related to the prevention and management of concussions. METHODS: A mail questionnaire was administered to all eligible high school coaches who received the tool kit. Follow-up focus groups were conducted for additional information. Both quantitative data from the surveys and qualitative data from the focus groups were analyzed to support the objectives of the study. RESULTS: Respondents self-reported favorable changes in knowledge, attitudes, and practices toward the prevention and management of concussions. Qualitative responses augmented the quantitative data. CONCLUSION: Barriers to concussion prevention and management are complex; however, these results highlight the role that coaches can play in school settings in establishing a safe environment for their athletes.


Assuntos
Conscientização , Concussão Encefálica/prevenção & controle , Centers for Disease Control and Prevention, U.S. , Instituições Acadêmicas , Adolescente , Traumatismos em Atletas/prevenção & controle , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Desenvolvimento de Programas , Esportes , Inquéritos e Questionários , Ensino/métodos , Estados Unidos
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