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1.
J Mol Cell Cardiol ; 187: 65-79, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38181546

RESUMO

BACKGROUND: Vascular calcification (VC) is a prevalent independent risk factor for adverse cardiovascular events and is associated with diabetes, hypertension, chronic kidney disease, and atherosclerosis. However, the mechanisms regulating the osteogenic differentiation of vascular smooth muscle cells (VSMC) are not fully understood. METHODS: Using hydrogels of tuneable stiffness and lysyl oxidase-mediated stiffening of human saphenous vein ex vivo, we investigated the role of substrate stiffness in the regulation of VSMC calcification. RESULTS: We demonstrate that increased substrate stiffness enhances VSMC osteogenic differentiation and VSMC calcification. We show that the effects of substrate stiffness are mediated via a reduction in the level of actin monomer within the nucleus. We show that in cells interacting with soft substrate, elevated levels of nuclear actin monomer repress osteogenic differentiation and calcification by repressing YAP-mediated activation of both TEA Domain transcription factor (TEAD) and RUNX Family Transcription factor 2 (RUNX2). CONCLUSION: This work highlights for the first time the role of nuclear actin in mediating substrate stiffness-dependent VSMC calcification and the dual role of YAP-TEAD and YAP-RUNX2 transcriptional complexes.


Assuntos
Actinas , Calcificação Vascular , Humanos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Músculo Liso Vascular , Osteogênese , Células Cultivadas , Miócitos de Músculo Liso
2.
J Neuroinflammation ; 19(1): 99, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35459147

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease that impacts nearly 400 million people worldwide. The accumulation of amyloid beta (Aß) in the brain has historically been associated with AD, and recent evidence suggests that neuroinflammation plays a central role in its origin and progression. These observations have given rise to the theory that Aß is the primary trigger of AD, and induces proinflammatory activation of immune brain cells (i.e., microglia), which culminates in neuronal damage and cognitive decline. To test this hypothesis, many in vitro systems have been established to study Aß-mediated activation of innate immune cells. Nevertheless, the transcriptional resemblance of these models to the microglia in the AD brain has never been comprehensively studied on a genome-wide scale. METHODS: We used bulk RNA-seq to assess the transcriptional differences between in vitro cell types used to model neuroinflammation in AD, including several established, primary and iPSC-derived immune cell lines (macrophages, microglia and astrocytes) and their similarities to primary cells in the AD brain. We then analyzed the transcriptional response of these innate immune cells to synthetic Aß or LPS and INFγ. RESULTS: We found that human induced pluripotent stem cell (hIPSC)-derived microglia (IMGL) are the in vitro cell model that best resembles primary microglia. Surprisingly, synthetic Aß does not trigger a robust transcriptional response in any of the cellular models analyzed, despite testing a wide variety of Aß formulations, concentrations, and treatment conditions. Finally, we found that bacterial LPS and INFγ activate microglia and induce transcriptional changes that resemble many, but not all, aspects of the transcriptomic profiles of disease associated microglia (DAM) present in the AD brain. CONCLUSIONS: These results suggest that synthetic Aß treatment of innate immune cell cultures does not recapitulate transcriptional profiles observed in microglia from AD brains. In contrast, treating IMGL with LPS and INFγ induces transcriptional changes similar to those observed in microglia detected in AD brains.


Assuntos
Doença de Alzheimer , Células-Tronco Pluripotentes Induzidas , Doenças Neurodegenerativas , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Técnicas de Cultura de Células , Humanos , Imunidade Inata , Células-Tronco Pluripotentes Induzidas/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/metabolismo , Doenças Neurodegenerativas/metabolismo
3.
Proc Biol Sci ; 288(1944): 20202770, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33563118

RESUMO

Studies increasingly show that social connectedness plays a key role in determining survival, in addition to natural and anthropogenic environmental factors. Few studies, however, integrated social, non-social and demographic data to elucidate what components of an animal's socio-ecological environment are most important to their survival. Female giraffes (Giraffa camelopardalis) form structured societies with highly dynamic group membership but stable long-term associations. We examined the relative contributions of sociability (relationship strength, gregariousness and betweenness), together with those of the natural (food sources and vegetation types) and anthropogenic environment (distance from human settlements), to adult female giraffe survival. We tested predictions about the influence of sociability and natural and human factors at two social levels: the individual and the social community. Survival was primarily driven by individual- rather than community-level social factors. Gregariousness (the number of other females each individual was observed with on average) was most important in explaining variation in female adult survival, more than other social traits and any natural or anthropogenic environmental factors. For adult female giraffes, grouping with more other females, even as group membership frequently changes, is correlated with better survival, and this sociability appears to be more important than several attributes of their non-social environment.


Assuntos
Girafas , Animais , Meio Ambiente , Feminino , Alimentos , Fatores Sociológicos
4.
Phytopathology ; 110(4): 822-833, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31829117

RESUMO

Phenotypic diversity among individuals defines the potential for evolutionary selection in a species. Phytophthora infestans epidemics are generally thought to be favored by moderate to low temperatures, but temperatures in many locations worldwide are expected to rise as a result of global climate change. Thus, we investigated variation among individuals of P. infestans for relative growth at different temperatures. Isolates of P. infestans came from three collections: (i) individual genotypes recently dominant in the United States, (ii) recently collected individuals from Central Mexico, and (iii) progeny of a recent sexual recombination event in the northeastern United States. In general, these isolates had optimal mycelial growth rates at 15 or 20°C. However, two individuals from Central Mexico grew better at higher temperatures than did most others and two individuals grew relatively less at higher temperatures than did most others. The isolates were also assessed for mefenoxam sensitivity and mating type. Each collection contained individuals of diverse sensitivities to mefenoxam and individuals of the A1 and A2 mating type. We then searched for genomic regions associated with phenotypic diversity using genotyping-by-sequencing. We found one single nucleotide polymorphism (SNP) associated with variability in mycelial growth at 20°C, two associated with variability in mycelial growth at 25°C, two associated with sensitivity to mefenoxam, and one associated with mating type. Interestingly, the SNPs associated with mefenoxam sensitivity were found in a gene-sparse region, whereas the SNPs associated with growth at the two temperatures and mating type were found both at more gene-dense regions.


Assuntos
Phytophthora infestans , Alanina/análogos & derivados , Estudo de Associação Genômica Ampla , México , New England , Doenças das Plantas , Polimorfismo de Nucleotídeo Único
5.
Oecologia ; 190(2): 375-385, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31155681

RESUMO

Emerging conservation efforts for the world's large predators may, if successful, restore natural predator-prey interactions. Marine reserves, where large predators tend to be relatively common, offer an experimental manipulation to investigate interactions between large-bodied marine predators and their prey. We hypothesized that southern stingrays-large, long-lived and highly interactive mesopredators-would invest in anti-predator behavior in marine reserves where predatory large sharks, the primary predator of stingrays, are more abundant. Specifically, we predicted southern stingrays in marine reserves would reduce the use of deep forereef habitats in the favor of shallow flats where the risk of shark encounters is lower. Baited remote underwater video was used to survey stingrays and reef sharks in flats and forereef habitats of two reserves and two fished sites in Belize. The interaction between "protection status" and "habitat" was the most important factor determining stingray presence. As predicted, southern stingrays spent more time interacting with baited remote underwater videos in the safer flats habitats, were more likely to have predator-inflicted damage inside reserves, and were less abundant in marine reserves but only in the forereef habitat. These results are consistent with a predation-sensitive habitat shift rather than southern stingray populations being reduced by direct predation from reef sharks. Our study provides evidence that roving predators can induce pronounced habitat shifts in prey that rely on crypsis and refuging, rather than active escape, in high-visibility, heterogeneous marine habitats. Given documented impacts of stingrays on benthic communities it is possible restoration of reef shark populations with reserves could induce reef ecosystem changes through behavior-mediated trophic cascades.


Assuntos
Ecossistema , Tubarões , Animais , Belize , Comportamento Predatório
6.
Psychooncology ; 24(3): 341-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25116753

RESUMO

OBJECTIVE: Prostate cancer is one of the mostly commonly diagnosed cancers in men. Unfortunately, the treatment for this cancer can have a number of negative side effects, both for the man himself and his partner. This study investigated the support needs of both men and partners throughout the prostate cancer journey and how this journey may be optimally managed. METHODS: Thirty-one men who had undergone prostate cancer treatment within the last 6 years and 31 partners answered a questionnaire, which explored support care issues as identified in the literature and from focus groups. RESULTS: Men and partners were moderately satisfied with information given regarding diagnosis, treatment and side effects, but partners were more satisfied with information relating to the particular chosen treatment. Men's understanding of their chosen treatment's potential side effects was significantly different from their understanding of diagnosis, cancer outcome, treatment options and selected treatment. Timing of information delivery was preferred by men at diagnosis, whereas partners preferred after the diagnosis. Men wanted more time to think about the diagnosis and treatment, whereas partners wanted an opportunity to discuss the diagnosis. The management of common side effects such as emotional changes, incontinence and erectile dysfunction was rated as 'somewhat' satisfactory. CONCLUSION: Men and partners may have different educational and supportive needs throughout the prostate cancer journey that require attention and tailored management.


Assuntos
Disfunção Erétil/psicologia , Necessidades e Demandas de Serviços de Saúde , Satisfação Pessoal , Neoplasias da Próstata/terapia , Parceiros Sexuais/psicologia , Cônjuges , Adaptação Psicológica , Idoso , Idoso de 80 Anos ou mais , Disfunção Erétil/etiologia , Feminino , Grupos Focais , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/psicologia , Qualidade de Vida , Apoio Social , Inquéritos e Questionários
7.
Pharmacopsychiatry ; 48(4-5): 170-5, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26181194

RESUMO

INTRODUCTION: Armodafinil, a moderate inducer of cytochrome P450 (CYP) 3A4, has been studied as adjunctive therapy to maintenance medications for major depressive episodes associated with bipolar I disorder. We evaluated the effect of daily dosing with armodafinil on the pharmacokinetics and safety of the CYP3A4 substrate aripiprazole, an atypical antipsychotic used to treat bipolar I disorder. METHODS: Healthy adults received 15 mg aripiprazole alone and after armodafinil (250 mg/day) pretreatment. Pharmacokinetic parameters were derived from plasma concentrations of aripiprazole and its active metabolite, dehydro-aripiprazole, obtained over 16 days after each aripiprazole administration. Steady-state pharmacokinetics of armodafinil and its 2 circulating metabolites was assessed. RESULTS: Of 36 subjects enrolled, 24 were evaluable for pharmacokinetic analysis. Armodafinil reduced systemic exposure to aripiprazole (Cmax, - 8%; AUC0-∞, -34%) and dehydro-aripiprazole, which is both formed and eliminated in part via CYP3A4 (Cmax, - 10%; AUC0-∞, - 32%). Adverse events were generally consistent with known safety profiles of each agent. DISCUSSION: Systemic exposure to aripiprazole and dehydro-aripiprazole was moderately reduced following armodafinil pretreatment. The combination was generally well tolerated under the conditions studied.


Assuntos
Antipsicóticos/farmacocinética , Aripiprazol/farmacocinética , Compostos Benzidrílicos/farmacologia , Indutores do Citocromo P-450 CYP3A/farmacologia , Promotores da Vigília/farmacologia , Adolescente , Adulto , Antipsicóticos/efeitos adversos , Área Sob a Curva , Aripiprazol/efeitos adversos , Compostos Benzidrílicos/efeitos adversos , Indutores do Citocromo P-450 CYP3A/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila , Piperazinas/metabolismo , Quinolonas/metabolismo , Promotores da Vigília/efeitos adversos , Adulto Jovem
8.
J Fish Biol ; 87(6): 1322-41, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26709210

RESUMO

This study documents and discusses recent (2002-2015) sightings and captures of smalltooth sawfish Pristis pectinata in the Bahamas. Movement patterns and habitat preferences of five P. pectinata are examined: two tracked with acoustic telemetry in Bimini and three tagged with pop-up archival transmitting tags in Andros. Historically, P. pectinata may have been distributed throughout the Bahamas; however, since 2002 only 61 encounters were recorded including: Andros (30), Bimini (19) and a handful across other Islands (12). In Bimini, all P. pectinata were >225 cm (stretched total length, LST) suggesting that it is not used as a nursery area. Pristis pectinata in Andros ranged from c. 80 to 450 cm (LST) indicating that this island might be an important nursery and breeding habitat. Pristis pectinata tracked in both islands remained at depths <3 m, often adjacent to mangrove habitats, displaying residency from 42 days (Bimini) to 180 days (Andros). These preliminary findings confirm the Bahamas as an important habitat for P. pectinata and emphasize the urgent need for national protection and management of this population.


Assuntos
Comportamento Animal , Ecossistema , Rajidae/fisiologia , Animais , Bahamas , Espécies em Perigo de Extinção , Feminino , Comportamento de Retorno ao Território Vital , Masculino , Densidade Demográfica
9.
J Fish Biol ; 85(5): 1429-45, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25131145

RESUMO

This study employed a combination of otolith microchemistry to indicate the recent habitat use, and plasma concentrations of the hormone insulin-like growth factor 1 (IGF1) as an index of recent growth rate, to demonstrate differences in growth and habitat use by Dolly Varden Salvelinus malma occupying both freshwater and estuarine habitats in south-west Alaska. Extensive sampling in all habitats revealed that fish had higher IGF1 levels in estuarine compared to lake habitats throughout the summer, and that the growth rates in different habitats within the estuary varied seasonally. In addition, otolith microchemistry indicated differentiation in estuarine habitat use among individual S. malma throughout summer months. Although growth in the estuary was higher than in fresh water in nearly all sites and months, the benefits and use of the estuarine habitats varied on finer spatial scales. Therefore, this study further illustrates the diverse life histories of S. malma and indicates an evaluation of the benefits of marine waters needs to include sub-estuary scale habitat use.


Assuntos
Ecossistema , Fator de Crescimento Insulin-Like I/química , Membrana dos Otólitos/química , Truta/crescimento & desenvolvimento , Alaska , Animais , Estuários , Água Doce , Estações do Ano , Truta/sangue
10.
Osteoarthritis Cartilage ; 20(6): 541-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22425883

RESUMO

OBJECTIVE: To assess the responsiveness of the Intermittent and Constant Osteoarthritis Pain (ICOAP) measure, Hip Disability and Osteoarthritis Outcome Score Physical Function Short Form (HOOS-PS), and the Knee Disability and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS) in a pharmacological trial. METHODS: Data were obtained from a randomized double-blind trial comparing naproxcinod with naproxen and ibuprofen in individuals with hip or knee osteoarthritis (OA) (NCT00662896). Participants completed the ICOAP, HOOS-PS/KOOS-PS, and Western Ontario and McMaster Universities OA Index (WOMAC) Likert version 3.0 before and 13 weeks after treatment. In hip and knee OA participants separately, the mean pre-post treatment change in scores, effect size (ES) and standardized response mean (SRM) were determined for each measure by treatment arm, and for all arms combined. RESULTS: Of 349 trial participants, 156 with knee OA and 48 with hip OA completed all measures at both time-points and were included (mean age 61 years; two-thirds female). Although there was both within treatment and between treatment variability in response, among knee OA participants, ICOAP intermittent, constant, and total scores and KOOS-PS scores showed, on average, moderate effects, with ESs ranging from 0.46 to 0.54 and SRMs from 0.49 to 0.56. Similar changes were seen for the WOMAC pain and function subscales (0.58 and 0.58, respectively). In those with hip OA, no significant improvement in symptoms was seen for any measure. CONCLUSION: Responsiveness to pharmaceutical intervention was demonstrated for ICOAP and KOOS-PS among participants with knee OA. Absence of treatment response precluded assessment of responsiveness in hip OA.


Assuntos
Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Índice de Gravidade de Doença , Idoso , Analgésicos não Narcóticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Avaliação da Deficiência , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Ibuprofeno/uso terapêutico , Masculino , Pessoa de Meia-Idade , Naproxeno/análogos & derivados , Naproxeno/uso terapêutico , Doadores de Óxido Nítrico/uso terapêutico , Osteoartrite do Quadril/complicações , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/fisiopatologia , Dor/tratamento farmacológico , Dor/etiologia , Medição da Dor/métodos , Resultado do Tratamento
11.
Clin Otolaryngol ; 37(5): 342-54, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22928754

RESUMO

BACKGROUND: In the UK, approximately 10 000 people have cochlear implants, more than 99% with a unilateral implant. Evidence shows that adults implanted bilaterally may benefit from binaural advantages; however, systematic review evidence is limited. OBJECTIVES OF THE REVIEW: To conduct a systematic review to discover the evidence for effectiveness and cost-effectiveness of using bilateral cochlear implants in adults with severe-to-profound hearing loss by comparing their effectiveness with unilateral cochlear implantation or unilateral cochlear implantation and acoustic hearing aid in the contralateral ear. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: This examined 16 electronic databases, plus bibliographies and references for published and unpublished studies. EVALUATION METHOD: Abstracts were independently assessed against inclusion criteria by two researchers, and disagreements were resolved. Selected papers were then retrieved and further independently assessed in a similar way. Included studies had their data extracted by one reviewer and checked by another. RESULTS: Searches yielded 2892 abstracts producing 19 includable studies. Heterogeneity between studies precluded meta-analysis. However, all studies reported that bilateral cochlear implants improved hearing and speech perception: one randomised controlled trial found a significant binaural benefit over the first ear alone for speech and noise from the front (12.6 ± 5.4%, P < 0.001) and when noise was ipsilateral to the first ear (21 ± 6%, P < 0.001); and another found a significant benefit for spatial hearing at 3 and 9 months post-implantation compared with pre-implantation [mean difference (sd) scores: 3 months = 1.46 (0.83-2.09), P < 0.01].Quality of life results varied, showing bilateral implantation may improve quality of life in the absence of worsening tinnitus. Limited cost-effectiveness evidence showed that bilateral implantation is probably only cost-effective at a willingness-to-pay threshold above £62 000 per quality adjusted life year. CONCLUSIONS: Despite inconsistency in the quality of available evidence, the robustness of systematic review methods gives weight to the positive findings of included studies demonstrating that bilateral implantation is clinically effective in adults but unlikely to be cost-effective.


Assuntos
Implantes Cocleares/economia , Surdez/economia , Surdez/reabilitação , Adulto , Análise Custo-Benefício , Humanos , Reino Unido
12.
J Environ Radioact ; 243: 106810, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34990898

RESUMO

Tritiated water (HTO), tissue free water tritium (TFWT) and organically bound tritium (OBT) activity concentrations in soil and plant leaves, collected at background areas in Ontario, were measured to quantify the current tritium baseline. Five representative background sites, based on their geological characteristics and residential populations, have been selected for this study. Undisturbed soils, plant leaves and surface water samples were collected at 5 sites (London, Kapuskasing, Thunder Bay, Elliot Lake and Cornwall areas) in 2015. Water sample HTO activity concentrations were measured using Liquid Scintillation Counting (LSC, ALOKA), and HTO activity concentrations for soil and TFWT for plant leaves were measured by LSC (Quantulus 1220) on water extracted from frozen samples using a freeze-drying vacuum system equipped with a liquid nitrogen trap. Plant leaf OBT levels were obtained by combustion of rinsed freeze-dried samples using a Parr combustion system, while soil OBT values were obtained using a tube furnace combustion system. Combustion water was distilled before being counted by LSC (Quantulus 1220). HTO activity concentrations were found to range between 1.4 and 2.0 Bq/L (MDA = 0.5 Bq/L) in surface water and soil samples. TFWT values were less than the minimum detectable activity (MDA = 3.5 Bq/L) in plant leaves. In contrast, OBT activity concentrations (MDA = 5 Bq/L) ranged from 5.7 to 17.1 Bq/L in plant leaves and 8.3-20.7 Bq/L in surface soil (0-5 cm depth). The overall OBT activity concentrations were higher in the London and the Cornwall areas. Lower levels were measured near Thunder Bay, Kapuskasing and Elliot Lake. There was no obvious relationship between soil OBT activity concentrations and soil types. The results provide the current tritium (HTO, TFWT and OBT) baseline values in Ontario. These values will be helpful for use as background locations for the evaluation of past and future environmental tritium inputs associated with nuclear facilities, and will be taken into account when evaluating the environmental impact of nuclear facilities in Ontario. Since samples in this study were primarily taken in wooded areas, some questions remain regarding the possibility that soil samples in open, non-wooded areas could show different HTO and OBT contents than those presented in this study.


Assuntos
Monitoramento de Radiação , Poluentes Radioativos do Solo , Ontário , Solo , Poluentes Radioativos do Solo/análise , Trítio/análise
13.
J Affect Disord ; 296: 541-548, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606804

RESUMO

BACKGROUND: The Affective Symptoms Scale (ASRS) is a unique instrument designed to separately measure depressive and manic symptoms in mood disorders. We validated the ASRS against the Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS-16). METHODS: A retrospective study of 258 patients who completed the PHQ-9, QIDS-16 and ASRS as part of routine clinical care. To establish meaningful clinical thresholds for the depression subscale of the ASRS, it was equated with the QIDS and the PHQ-9. RESULTS: The depression subscale of the ASRS had significant positive correlations with the QIDS-16 and the PHQ-9 (respectively, r= 0.8, t[253] = 19.8, p < 0.001, and r= 0.8, t[245] = 28.2, p < 0.001). The equipercentile equating method with the PHQ-9 indicated that the thresholds corresponded to ASRS depression subscale scores of 5.4, 10.6, 16.1, and 23. Equating with the QIDS indicated that thresholds corresponded to ASRS depression subscale scores of 5.1, 11, 18.4, and 27.5. LIMITATIONS: Limitations include a small sample size that did not allow more detailed statistical analysis, such as Item Response Theory. The population is a heterogenous population at a university outpatient setting. CONCLUSIONS: The ASRS depression subscale significantly correlated with the PHQ-9 and QIDS-16. Our proposed threshold scores for the ASRS are 5, 11, 16 and 23 to indicated mild, moderate, severe and very severe depression respectively.


Assuntos
Depressão , Depressão/diagnóstico , Humanos , Escalas de Graduação Psiquiátrica , Psicometria , Estudos Retrospectivos , Autorrelato
15.
Matern Child Health J ; 15(4): 425-30, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21472512

RESUMO

Efforts to reduce infant mortality in the United States have failed to incorporate paternal involvement. Research suggests that paternal involvement, which has been recognized as contributing to child development and health for many decades, is likely to affect infant mortality through the mother's well-being, primarily her access to resources and support. In spite of that, systemic barriers facing the father and the influence on his involvement in the pregnancy have received little attention. The Commission on Paternal Involvement in Pregnancy Outcomes (CPIPO) has identified the most important social barriers to paternal involvement during pregnancy and outlined a set of key policy priorities aimed at fostering paternal involvement. This article summarizes the key recommendations, including equitable paternity leave, elimination of marriage as a tax and public assistance penalty, integration of fatherhood initiatives in MCH programs, support of low-income fathers through employment training, father inclusion in family planning services, and expansion of birth data collection to include father information.


Assuntos
Comportamento Paterno , Formulação de Políticas , Comitês Consultivos , Emprego , Feminino , Política de Saúde , Humanos , Licença Parental/legislação & jurisprudência , Gravidez , Impostos/legislação & jurisprudência , Estados Unidos
16.
J Exp Med ; 170(6): 2081-95, 1989 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-2531194

RESUMO

A cytokine synthesis inhibitory factor (CSIF) is secreted by Th2 clones in response to Con A or antigen stimulation, but is absent in supernatants from Con A-induced Th1 clones. CSIF can inhibit the production of IL-2, IL-3, lymphotoxin (LT)/TNF, IFN-gamma, and granulocyte-macrophage CSF (GM-CSF) by Th1 cells responding to antigen and APC, but Th2 cytokine synthesis is not significantly affected. Transforming growth factor beta (TGF-beta) also inhibits IFN-gamma production, although less effectively than CSIF, whereas IL-2 and IL-4 partially antagonize the activity of CSIF. CSIF inhibition of cytokine synthesis is not complete, since early cytokine synthesis (before 8 h) is not significantly affected, whereas later synthesis is strongly inhibited. In the presence of CSIF, IFN-gamma mRNA levels are reduced slightly at 8, and strongly at 12 h after stimulation. Inhibition of cytokine expression by CSIF is not due to a general reduction in Th1 cell viability, since actin mRNA levels were not reduced, and proliferation of antigen-stimulated cells in response to IL-2, was unaffected. Biochemical characterization, mAbs, and recombinant or purified cytokines showed that CSIF is distinct from IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IFN-gamma, GM-CSF, TGF-beta, TNF, LT, and P40. The potential role of CSIF in crossregulation of Th1 and Th2 responses is discussed.


Assuntos
Fatores Biológicos/fisiologia , Linfócitos T Auxiliares-Indutores/fisiologia , Animais , Fatores Biológicos/isolamento & purificação , Células Clonais , Citocinas , Interferon gama/biossíntese , Interleucina-2/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , RNA Mensageiro/análise , Linfócitos T Auxiliares-Indutores/análise
17.
J Exp Med ; 173(2): 507-10, 1991 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-1899106

RESUMO

We have characterized the mast cell stimulating activity of murine cytokine synthesis inhibitory factor, referred to as interleukin 10 (IL-10). It was found that IL-10 alone failed to support the growth of mast cell lines and mast cell progenitors. Nevertheless, it dramatically enhanced their growth when combined with IL-3 or IL-4. Moreover, IL-4 plus IL-10 supported the proliferation of mast cells as well as IL-3, suggesting that these two factors may provide a pathway for their development independent of IL-3. However, optimal mast cell growth was stimulated by the combination of IL-10, IL-4, and IL-3. This particular set of cytokines are coordinately produced by activated T cells and may constitute an effective network regulating early and late stages of mast cell development during certain immune responses.


Assuntos
Interleucinas/fisiologia , Mastócitos/citologia , Animais , Divisão Celular , Linhagem Celular , Interleucina-10 , Interleucina-3/fisiologia , Interleucina-4/fisiologia , Mastócitos/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Endogâmicos , Proteínas Recombinantes
18.
J Exp Med ; 159(1): 179-92, 1984 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-6420495

RESUMO

Most mouse strains are able to mount a diverse antibody response against group A streptococcal carbohydrate (GAC). We have previously reported that murine anti-GAC antibodies are for the most part restricted to IgM and IgG3 subclasses. In addition, despite extensive heterogeneity in their isoelectric focusing patterns, greater than 50% of A/J anti-GAC antibodies share a common light chain defined by spectrotypic and idiotypic (VK1GAC) criteria. We have used protein and DNA sequencing strategies to examine the genetic basis of diversity in murine anti-GAC antibodies. In particular, we report that, (a) multiple, closely homologous VH gene segments contribute to the generation of anti-GAC antibodies, (b) a common framework sequence, related to the VK27 subgroup, probably defines VK1GAC, and (c) the A/J anti-GAC VH regions and BALB/c anti-inulin VH sequences are 95% homologous at the protein level and are likely encoded by overlapping VH gene families. Lastly, we discuss the genetic mechanisms that might permit the evolution of multiple, closely homologous germline VH gene segments in the context of highly divergent flanking region sequences.


Assuntos
Anticorpos Antibacterianos/genética , Código Genético , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Polissacarídeos Bacterianos/genética , Alelos , Animais , Anticorpos Antibacterianos/biossíntese , Diversidade de Anticorpos , Clonagem Molecular , Hibridomas/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/imunologia , Inulina/imunologia , Camundongos , Camundongos Endogâmicos A , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fosforilcolina/imunologia , Polissacarídeos Bacterianos/imunologia
19.
J Exp Med ; 157(1): 130-40, 1983 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-6184438

RESUMO

The combining sites of 12 mouse hybridoma antibodies to dextran B1355S have been characterized by quantitative precipitin assay. All antibodies preferentially bind the immunizing antigen B1355S and two other class I dextrans, B1498S and B1501S, but show substantial differences in the extents to which they cross react with class I dextrans, suggesting their clustering into five groups. Three myeloma proteins, CAL20 TEPC1035, J558, and MOPC104E, which bind dextran B1355S, each fall into a different group. There appears to be a substantial, but imperfect, correlation of DH region structure and individual idiotypic determinants with dextran binding patterns. Proteins with RY DH segments and IdI (J558) idiotypes are in groups 1 or 3, and proteins with YD DH segments and IdI (MOPC104E) idiotypes are exclusively in group 5. However, identical patterns of precipitin curves accompany very different sequences in CDR3. Antibodies of group 1, which react only with class II dextrans, differ the most in primary sequence, a finding suggesting that subsites responsible for cross reactivity with class I dextrans may be blocked and that this may be effected by side chains of different amino acids. This finding delineates a new aspect of the relationship of variability in amino acid sequence to antibody complementarity.


Assuntos
Anticorpos Monoclonais/imunologia , Dextranos/imunologia , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Cadeias Pesadas de Imunoglobulinas/genética , Idiótipos de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/genética , Camundongos , Proteínas do Mieloma/imunologia , Relação Estrutura-Atividade
20.
Curr Opin Obstet Gynecol ; 22(6): 525-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20930631

RESUMO

PURPOSE OF REVIEW: To review current research, policy, and practice on paternal involvement in pregnancy outcomes and suggest recommendations to improve paternal involvement in pregnancy and childbirth. RECENT FINDINGS: Although much has been written about fathers' influence on child health and development, little is known about the expectant father's role in pregnancy and childbirth. Recent studies have demonstrated the importance of paternal involvement during pregnancy, but more research is needed to identify specific contributions expectant fathers make and their impact on reducing infant mortality and associated risk factors during pregnancy and childbirth. SUMMARY: Obstetricians-gynecologists can play a greater role in promoting research, policy and practice to improve paternal involvement in pregnancy and childbirth.


Assuntos
Pai , Promoção da Saúde , Comportamento Paterno , Papel do Médico , Resultado da Gravidez , Pesquisa Biomédica , Feminino , Política de Saúde , Humanos , Masculino , Gravidez
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