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1.
Hum Reprod ; 37(9): 2087-2094, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-35906918

RESUMO

STUDY QUESTION: Are donor-conceived people (DCP) willing to utilize donor gametes themselves if unable to conceive spontaneously? SUMMARY ANSWER: The majority of DCP would consider or are undecided about utilizing donor gametes and those who would consider the utilization are more likely to have been told about their donor-conceived origins at a young age by a family member and have overall positive experiences as a DCP. WHAT IS KNOWN ALREADY: DCP view their donor conception as an important part of their self-identity and many desire contact with genetically related individuals. Additionally, many believe that sperm donation should only be practiced if identifying information on the donor is provided. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study using a Web-based survey that was disseminated from 6 March to 15 August 2021. A total of 528 participants completed the questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS: The researcher-created survey was sent to registered users of the Donor Sibling Registry (DSR) who were conceived via donor-assisted reproduction and were 18 years of age or older. The survey was optional and anonymous, and the main outcome measure was the willingness to use donated gametes if unable to spontaneously conceive. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 528 participants who completed the survey, 40.2% (212/528) have or would consider using donor gametes themselves if unable to conceive spontaneously and 24.6% (130/528) were undecided. Those who had used or were undecided about the utilization were significantly younger (26 years vs. 31 years, P < 0.001) and less likely to be married (32.7% vs. 47.3%, P < 0.001) than those who would not consider using donor gametes. They were also less likely to self-identify as female (78.9% vs. 86.6%, P = 0.03) but had no difference in sexual orientation (P = 0.13). Additionally, they were more likely to have known about their donor-conceived origins for more years (18 (0-50) vs. 11 (0-61), P = 0.004), be informed by a family member (75.5% vs. 65.6%, P = 0.001) and have overall positive feelings about being conceived using a donor (93.0% vs. 52.5%, P < 0.001). LIMITATIONS, REASONS FOR CAUTION: A major limitation is that DSR participants may not be representative of all DCP. Additionally, analyzing the DCP who stated that they were undecided about using donor gametes into the 'would consider' group may be overestimating the openness to utilization in this group. WIDER IMPLICATIONS OF THE FINDINGS: The findings from this study give new insight for health care workers to further counsel patients who are considering using third-party reproduction by providing reassurance that the majority of their future children would consider similar means, if needed, to achieve their family-building goals. STUDY FUNDING/COMPETING INTEREST(S): Funding for this study was received from the Department of Obstetrics and Gynecology Division of Reproductive Endocrinology and Infertility, University of Colorado. All authors declare that there are no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Revelação , Sêmen , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Reprodução , Doadores de Tecidos
2.
Ultrasound Obstet Gynecol ; 55(6): 776-785, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31613023

RESUMO

OBJECTIVES: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value. METHODS: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra- and extra-abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome. RESULTS: Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty-one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA-PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra- and extra-abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra-abdominal bowel diameter ≥ 97.7th percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02-2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%). CONCLUSIONS: This large prospective longitudinal study found that intra-abdominal bowel dilatation when present repeatedly during fetal development can differentiate between simple and complex gastroschisis; however, the positive predictive value is low, and therefore the clinical usefulness of this marker is limited. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Feto/diagnóstico por imagem , Gastrosquise/diagnóstico por imagem , Ultrassonografia Pré-Natal/estatística & dados numéricos , Abdome/embriologia , Biomarcadores/análise , Biometria , Diagnóstico Diferencial , Feminino , Morte Fetal/etiologia , Gastrosquise/embriologia , Idade Gestacional , Humanos , Recém-Nascido , Intestinos/embriologia , Modelos Lineares , Modelos Logísticos , Estudos Longitudinais , Artéria Mesentérica Superior/embriologia , Poli-Hidrâmnios/diagnóstico por imagem , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Fluxo Pulsátil , Medição de Risco , Natimorto
3.
Int J Pharm ; 572: 118753, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678380

RESUMO

BACKGROUND: Perfluorocarbon-nanoemulsions (PFC-NE) made of PFC and phospholipids (PL) by homogenization are optimal for in vivo-19F labelling of monocytes and subsequently of inflamed tissues in magnetic resonance imaging (MRI). Necessary requirements for in vivo use of PFC-NE are sterility, suitable droplet sizes and the absence of immune activating liposomes, which are a typical byproduct of the homogenization process. METHODS AND RESULTS: To meet these requirements, we developed an aseptic in-vial preparation technique for PFC-NE based on dual centrifugation (DC) by testing different PFC/phospholipid ratios as well as the application of additives. Two different PFC, perfluorooctylbromide (PFOB) and perfluoro-15-crown-5-ether (PFCE), were investigated. Particle sizes were assessed by dynamic light scattering and NE morphology by cryoTEM. DC homogenization was optimal when using an excess of PL (8.7 % (m/m) of utilized PFC, z-ave: 180 nm, pdi: 0.2). A purification approach by centrifugation was implemented to remove liposomes formed from the excess of PL during homogenization. The purification success was proven by phospholipid assay and PFC quantification via density and sound velocity measurements. CONCLUSION: DC in combination with a short centrifugation is a fast and reliable way of small-scale aseptic PFC-NE production for 19F MRI passive-targeting experiments of monocytes and inflamed tissues.


Assuntos
Emulsões/química , Fluorocarbonos/química , Nanopartículas/química , Centrifugação/métodos , Éteres de Coroa/química , Difusão Dinâmica da Luz/métodos , Lipossomos/química , Imageamento por Ressonância Magnética/métodos , Tamanho da Partícula , Fosfolipídeos/química
4.
Eur J Pharm Biopharm ; 142: 114-122, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220572

RESUMO

BACKGROUND: Perfluorocarbon (PFC)-nanoemulsions (NE) are a convenient tool for 19F magnetic resonance imaging in cell and animal experiments. Typical preparation methods, like high-pressure homogenization or microfluidization, produce nanoemulsions in mL-scale. However, experiments usually require only miniscule amounts of PFC-NE, several 100 µL. For site-specific imaging tissue-specific ligands, e.g. peptides or antibodies, are covalently bound to the NE surface. This requires the use of expensive functionalized phospholipids containing reactive groups (e.g. maleimide), which often deteriorate quickly in liquid storage, rendering the manufacturing process highly cost-inefficient. A technique to manufacture storage stable NE that maintain their functionality for coupling of various ligands is desired. METHODS AND RESULTS: Different PFC-NE formulations and preparation techniques were compared and the most suitable of these was tested in short-, as well as long-term stability tests. Droplet size stability was investigated by dynamic light scattering and cryogenic transmission electron microscopy over 1.5 a. Surface modifiability was assessed by a fluorescence assay. The utility of these NE was proven in an in vitro model. CONCLUSION: The established PFC-NE platform offers a cost-efficient way to produce larger amounts of long-term storable imaging agents, which can be surface-modified on demand for application in targeted 19F MRI.


Assuntos
Emulsões/química , Flúor/química , Fluorocarbonos/química , Nanopartículas/química , Nanoestruturas/química , Meios de Contraste/química , Difusão Dinâmica da Luz/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Microscopia Eletrônica de Transmissão/métodos , Tamanho da Partícula
5.
Photochem Photobiol Sci ; 17(1): 27-34, 2018 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-29143029

RESUMO

The products from the 193 nm irradiation of triphenylsulfonium nonaflate (TPS) embedded in a poly(methyl methacrylate) (PMMA) film have been characterized. The analysis of the photoproduct formation was performed using chromatographic techniques including HPLC, GPC and GC-MS as well as UV-vis and NMR spectroscopic methods. Two previously unreported TPS photoproducts, triphenylene and dibenzothiophene, were detected; additionally, GPC and DOSY-NMR spectroscopic analyses after irradiation suggested that TPS fragments had been incorporated into the polymer film. The irradiation of acetonitrile solutions containing 10% w/v PMMA and 1% w/v TPS in a 1 cm-path-length cuvette showed only a trace amount of triphenylene or dibenzothiophene, indicating that topochemical factors were important for the formation of these molecules. The accumulated evidence indicates that both products were formed by in-cage, secondary photochemical reactions: 2-(phenylthio)biphenyl to triphenylene, and diphenylsulfide to dibenzothiophene.

6.
Ned Tijdschr Geneeskd ; 160: D284, 2016.
Artigo em Holandês | MEDLINE | ID: mdl-27552936

RESUMO

- In 90% of children, blunt abdominal trauma is the cause of renal, splenic or hepatic injury or an injury affecting a combination of these organs.- Because children's kidneys are anatomically less protected than those of adults, potential renal injury following direct trauma affecting the child's flank, for example by a handlebar or knee should be considered.- Symptoms of renal trauma include excoriations or haematoma on the flank, a 'seatbelt-sign', macroscopic haematuria and fractures of the ribs and vertebra.- As haematuria does not correlate with the severity of renal injury, all children with persistent haematuria should undergo renal imaging.- Children without abnormalities on Doppler ultrasound examination and without macroscopic haematuria can be discharged from the emergency room.- Conservative management of blunt renal trauma is indicated for all haemodynamically stable children. However, haemodynamically unstable children need to undergo an urgent laparotomy. The routine use of bed rest is only indicated for grade V renal injuries.- A DMSA scan is recommended 6-12 weeks after trauma for grade IV-V renal injury.


Assuntos
Rim/lesões , Ferimentos não Penetrantes/diagnóstico , Criança , Tratamento Conservador , Hematoma/etiologia , Hematúria/etiologia , Humanos , Rim/diagnóstico por imagem
7.
Diabetes Obes Metab ; 18(1): 6-15, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26228188

RESUMO

Diabetes mellitus is a growing worldwide epidemic disease, currently affecting 1 in 12 adults. Treatment of disease complications typically consumes ∼10% of healthcare budgets in developed societies. Whilst immune-mediated destruction of insulin-secreting pancreatic ß cells is responsible for Type 1 diabetes, both the loss and dysfunction of these cells underly the more prevalent Type 2 diabetes. The establishment of robust drug development programmes aimed at ß-cell restoration is still hampered by the absence of means to measure ß-cell mass prospectively in vivo, an approach which would provide new opportunities for understanding disease mechanisms and ultimately assigning personalized treatments. In the present review, we describe the progress towards this goal achieved by the Innovative Medicines Initiative in Diabetes, a collaborative public-private consortium supported by the European Commission and by dedicated resources of pharmaceutical companies. We compare several of the available imaging methods and molecular targets and provide suggestions as to the likeliest to lead to tractable approaches. Furthermore, we discuss the simultaneous development of animal models that can be used to measure subtle changes in ß-cell mass, a prerequisite for validating the clinical potential of the different imaging tracers.


Assuntos
Diabetes Mellitus/patologia , Células Secretoras de Insulina/patologia , Imagem Molecular/métodos , Adulto , Animais , Adesão Celular , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Medições Luminescentes , Manganês , Glicoproteínas de Membrana/metabolismo , Camundongos , Ratos , Receptores de Sulfonilureias/metabolismo , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Zinco
8.
Chem Sci ; 7(4): 2506-2515, 2016 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-28660020

RESUMO

Cobalt phthalocyanine (CoPc) is a known electrocatalyst for the carbon dioxide reduction reaction (CO2RR) that, when adsorbed onto edge-plane graphite (EPG) electrodes, shows modest activity and selectivity for CO production along with co-generation of H2. In contrast, electrodes modified with CoPc immobilized in a poly-4-vinylpridine (P4VP) film show dramatically enhanced activity and selectivity compared to those modified with CoPc alone. CoPc-P4VP films display a faradaic efficiency of ∼90% for CO, with a turnover frequency of 4.8 s-1 at just -0.75 V vs. RHE. Two properties of P4VP contribute to enhancing the activity of CoPc: (1) the ability of individual pyridine residues to coordinate to CoPc and (2) the high concentration of uncoordinated pyridine residues throughout the film which may enhance the catalytic activity of CoPc through secondary and other outer coordination sphere effects. Electrodes modified with polymer-free, five-coordinate CoPc(py) films (py = pyridine) and with CoPc catalysts immobilized in non-coordinating poly-2-vinylpyridine films were prepared to independently investigate the role that each property plays in enhancing CO2RR performance of CoPc-P4VP. These studies show that a synergistic relationship between the primary and outer coordination sphere effects is responsible for the enhanced catalytic activity of CoPc when embedded in the P4VP membrane.

9.
Genes Brain Behav ; 14(8): 641-54, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26463687

RESUMO

The genome of the white-throated sparrow (Zonotrichia albicollis) contains an inversion polymorphism on chromosome 2 that is linked to predictable variation in a suite of phenotypic traits including plumage color, aggression and parental behavior. Differences in gene expression between the two color morphs, which represent the two common inversion genotypes (ZAL2/ZAL2 and ZAL2/ZAL2(m) ), may therefore advance our understanding of the molecular underpinnings of these phenotypes. To identify genes that are differentially expressed between the two morphs and correlated with behavior, we quantified gene expression and terrirorial aggression, including song, in a population of free-living white-throated sparrows. We analyzed gene expression in two brain regions, the medial amygdala (MeA) and hypothalamus. Both regions are part of a 'social behavior network', which is rich in steroid hormone receptors and previously linked with territorial behavior. Using weighted gene co-expression network analyses, we identified modules of genes that were correlated with both morph and singing behavior. The majority of these genes were located within the inversion, showing the profound effect of the inversion on the expression of genes captured by the rearrangement. These modules were enriched with genes related to retinoic acid signaling and basic cellular functioning. In the MeA, the most prominent pathways were those related to steroid hormone receptor activity. Within these pathways, the only gene encoding such a receptor was ESR1 (estrogen receptor 1), a gene previously shown to predict song rate in this species. The set of candidate genes we identified may mediate the effects of a chromosomal inversion on territorial behavior.


Assuntos
Inversão Cromossômica , Comportamento Sexual Animal/fisiologia , Pardais/genética , Vocalização Animal/fisiologia , Agressão , Animais , Comportamento Animal/fisiologia , Receptor alfa de Estrogênio/genética , Feminino , Estudos de Associação Genética , Genoma , Masculino , Comportamento Social , Transcriptoma
10.
Facts Views Vis Obgyn ; 7(2): 91-100, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26175887

RESUMO

This study explores the attitudes and experiences of 57 sperm donors who responded to a survey posted online in the United States and indicated that they had had contact with their donor-conceived offspring or the parents of their donor-conceived offspring. On average, 18 years had elapsed since the respondents donated sperm. In the interim between donating and having contact with offspring, most had become curious about their offspring. Most made contact through a bank or online registry. Most respondents had communicated with at least one offspring at least once and most had exchanged photos with offspring. Approximately two-thirds had met in person once; the same proportion had communicated over email or text. Other forms of communication were less common. Almost half of the respondents now considered their donor-conceived offspring to be like a family member. At the same time, donors are respectful of the integrity of the family in which their offspring were raised. Donors with contact are open to having their partners and children know their donor-conceived offspring. Although contact is generally positive, donors report that establishing boundaries and defining the relationship can be very difficult. Some donors also urge those who are thinking of donating to consider the consequences and some suggest avoiding anonymity. There were no significant differences in attitudes and experiences between those who donated anonymously and those who had been identity-release for their offspring when they turned 18.

11.
Genes Immun ; 15(8): 543-55, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25101797

RESUMO

Major histocompatibility class II (MHC-II) expression is critical for immune responses and is controlled by the MHC-II transactivator CIITA. CIITA is primarily regulated at the transcriptional level and is expressed from three main promoters with myeloid, lymphoid and interferon (IFN)-γ-treated non-hematopoietic cells using promoters pI, pIII and pIV, respectively. Recent studies in non-hematopoietic cells suggest that a series of distal regulatory elements may be involved in regulating CIITA transcription. To identify distal elements in B cells, a DNase I hypersensitivity screen was performed, revealing a series of potential novel regulatory elements. These elements were analyzed computationally and biochemically. Several regions displayed active histone modifications and/or enhanced expression of a reporter gene. Four of the elements interacted with pIII in B cells. These same four regions were also found to interact with pI in splenic dendritic cells (spDC). Intriguingly, examination of the above interactions in pI-knockout-derived spDC showed a switch to the next available promoter, pIII. Extensive DNA methylation was found at the pI region in B cells, suggesting that this promoter is not accessible in B cells. Thus, CIITA expression is likely mediated in hematopoietic cells by common elements with promoter accessibility having a part in promoter choice.


Assuntos
Regulação da Expressão Gênica , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/genética , Sequências Reguladoras de Ácido Nucleico/genética , Transativadores/genética , Animais , Linfócitos B/metabolismo , Sítios de Ligação/genética , Fator de Ligação a CCCTC , Linhagem Celular Tumoral , Células Cultivadas , Metilação de DNA , Células Dendríticas/metabolismo , Desoxirribonuclease I/metabolismo , Linfócitos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Genéticos , Células Mieloides/metabolismo , Ligação Proteica , Isoformas de Proteínas/genética , Proteínas Repressoras/metabolismo
12.
Exp Clin Endocrinol Diabetes ; 121(10): 567-80, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24002899

RESUMO

Lipid-lowering drug therapy with statins has become a cornerstone to reduce and prevent atherosclerosis and its detrimental complications like cardiovascular diseases and stroke. Due to the multifactorial pathogenesis of atherosclerosis the search for novel lipid-modifying drugs is still one of the most active areas in research and development in the pharmaceutical industry. Currently, the focus lies on novel LDL-cholesterol lowering drugs with a higher efficacy and improved safety profile as well as on approaches to increase plasma levels and functionality of high-density lipoproteins (HDL) based on the inverse relationship between high plasma HDL-levels and the risk for cardiovascular diseases. Whereas the today clinically used lipid-modifying drugs are predominantly small molecules for oral drug therapy a significant percentage of the drug candidates currently in development are biological drugs such as monoclonal antibodies and antisense oligonucleotides. Up-to-date around 70 novel drug molecules acting on about 20 different molecular targets are in clinical and preclinical development with antibodies inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) being the most intensively investigated and competitive approach. The clinical results reported so far with these antibodies are very promising whereas the clinical benefit for prevention of atherosclerosis and cardiovascular diseases by pharmacologically increasing of plasma high-density lipoproteins still remains to be demonstrated. However, with the recent approval of 2 innovative drugs for the treatment of familial hypercholesterolemia and the promising clinical results of several novel drug candidates for LDL cholesterol lowering and high-density lipoprotein modulation one can expect the appearance of new drug breakthroughs for the treatment of dyslipidemia in the near future.


Assuntos
Doenças Cardiovasculares , LDL-Colesterol/sangue , Descoberta de Drogas , Transtornos do Metabolismo dos Lipídeos , Lipoproteínas HDL/sangue , Animais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Transtornos do Metabolismo dos Lipídeos/sangue , Transtornos do Metabolismo dos Lipídeos/tratamento farmacológico
13.
J Matern Fetal Neonatal Med ; 26(9): 946-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23311912

RESUMO

Complete liver herniation in abdominal wall defects without a membrane is rare and its prognosis is not well documented. We present a case diagnosed at 12 weeks of gestation. At 27 weeks, a C-section was performed for fetal distress. The infant proved impossible to ventilate and died. In literature, 16 similar cases are described of whom 14 died in the neonatal period and two in infancy. This suggests that herniation of the complete liver in isolated abdominal wall defects without a remnant membrane is lethal and counselling should be provided accordingly.


Assuntos
Parede Abdominal/anormalidades , Hérnia/diagnóstico por imagem , Hepatopatias/congênito , Anormalidades Múltiplas/diagnóstico por imagem , Adulto , Evolução Fatal , Feminino , Hérnia/complicações , Hérnia/congênito , Humanos , Recém-Nascido , Gravidez , Prognóstico , Ultrassonografia Pré-Natal
14.
Reprod Biomed Online ; 25(7): 670-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23063814

RESUMO

This study investigates the motivations, views and experiences of semen donors willing to have contact with their offspring. An online questionnaire for semen donors was posted by the US-based Donor Sibling Registry in 2009. A total of 164 respondents who had previously been donors completed the questionnaire, which consisted of 45 open and closed questions covering motivations for donating, health and medical information, experiences of donating, contact with offspring and implications of donating and contact for their families. The donors' primary motivation was to help other families, although payment was also a factor. Almost all donors were open to contact with their offspring and, where donors were partnered, three-quarters of the partners also supported possible contact. Almost one-third, however, had reservations about contact or were opposed. Two-thirds of donors' own children were interested in meeting the offspring. Contact between a donor and his offspring is often seen as a coming together of these two people only. The results of this study suggest that there are important ramifications for both of the families who become linked. Understanding gamete donation in this broader family context is crucial to the contribution that health professionals can make in this area.


Assuntos
Filhos Adultos/psicologia , Comunicação , Relações Familiares , Doadores de Tecidos/psicologia , Adolescente , Adulto , Confidencialidade/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Estudos Retrospectivos , Relações entre Irmãos , Inquéritos e Questionários , Adulto Jovem
15.
Genes Immun ; 13(4): 299-310, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22218223

RESUMO

Three distinct promoters control the master regulator of major histocompatibility complex (MHC) class II expression, class II transactivator (CIITA), in a cell type-specific manner. Promoter I (pI) CIITA, expressed primarily by dendritic cells (DCs) and macrophages, expresses a unique isoform that contains a caspase-recruitment domain (CARD). The activity and function of this isoform are not understood, but are believed to enhance the function of CIITA in antigen-presenting cells. To determine whether isoform I of CIITA has specific functions, CIITA mutant mice were created in which isoform I was replaced with isoform III sequences. Mice in which pI and the CARD-encoding exon were deleted were also created. No defect in the formation of CD4 T cells, the ability to respond to a model antigen or bacterial or viral challenge was observed in mice lacking CIITA isoform I. Although CIITA and MHC-II expression was decreased in splenic DCs, pI knockout animals expressed CIITA from downstream promoters, suggesting that control of pI activity is mediated by unknown distal elements that could act at pIII, the B-cell promoter. Thus, no critical function is linked to the CARD domain of CIITA isoform I with respect to basic immune system development, function and challenge.


Assuntos
Genes MHC da Classe II , Linfócitos/imunologia , Células Mieloides/imunologia , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas , Transativadores/metabolismo , Animais , Apresentação de Antígeno , Infecções por Arenaviridae/imunologia , Infecções por Arenaviridae/virologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/imunologia , Feminino , Listeriose/imunologia , Listeriose/microbiologia , Linfócitos/citologia , Linfócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides/citologia , Células Mieloides/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína , Relação Estrutura-Atividade , Transativadores/genética , Transativadores/imunologia
16.
Lab Anim ; 46(1): 32-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22087029

RESUMO

Male obese Zucker Diabetic Fatty (ZDF) rats develop type 2 diabetes around eight weeks of age, and are widely used as a model for human diabetes and its complications. The objective of the study was to test whether the complications manifested in the kidney and nerves of ZDF rats really correspond to human diabetic complications in their being related to the hyperglycaemic state. Four groups of ZDF rats were used. One lean (Fa/?) and one obese (fa/fa) untreated group served as non-diabetic and diabetic controls. In two further groups of obese (fa/fa) rats, diabetes was prevented by pioglitazone or delayed by food restriction. All rats were monitored up to 35 weeks of age with respect to their blood glucose, HbA1c and insulin levels, their kidney function (urinary glucose excretion, renal glucose filtration, glomerular filtration rate, albumin/creatinine ratio), and their nerve function (tactile and thermal sensory threshold and nerve conduction velocity). Pioglitazone prevented the development of diabetes, while food restriction delayed its onset for 8-10 weeks. Accordingly, kidney function parameters were similar to lean non-diabetic rats in pioglitazone-treated rats and significantly improved in food-restricted rats compared with obese controls. Kidney histology paralleled the functional results. By contrast, nerve functional evaluations did not mirror the differing blood glucose levels. We conclude that the ZDF rat is a good model for diabetic nephropathy, while alterations in nerve functions were not diabetes-related.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Animais , Análise Química do Sangue , Restrição Calórica , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Humanos , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Rim/patologia , Testes de Função Renal , Masculino , Condução Nervosa , Pioglitazona , Ratos , Ratos Zucker , Limiar Sensorial , Tiazolidinedionas/administração & dosagem
17.
Injury ; 43(9): 1442-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21129741

RESUMO

Minimal invasive surgery has not yet gained wide acceptation for the care of patients that sustained an abdominal trauma. We describe the complete laparoscopic surgical treatment of two patients after a single blunt abdominal trauma. One patient sustained a handle bar injury and presented with a gastric perforation. The other sustained a duodenal rupture by falling on a sharp edge of a table. The patients were assessed and treated laparoscopically. The perforations were identified and closed. Both patients had an uneventful postoperative recovery. Therapeutic laparoscopic treatment of patients with upper gastrointestinal perforation is feasible. We would recommend this approach to experienced laparoscopic surgeons in hemodynamically stable patients.


Assuntos
Traumatismos Abdominais/cirurgia , Duodeno/cirurgia , Perfuração Intestinal/cirurgia , Laparoscopia , Ferimentos não Penetrantes/cirurgia , Traumatismos Abdominais/complicações , Traumatismos Abdominais/fisiopatologia , Ciclismo/lesões , Criança , Duodeno/lesões , Duodeno/fisiopatologia , Humanos , Perfuração Intestinal/etiologia , Perfuração Intestinal/fisiopatologia , Masculino , Resultado do Tratamento , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/fisiopatologia
18.
Phys Rev E Stat Nonlin Soft Matter Phys ; 84(2 Pt 2): 026310, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21929093

RESUMO

Statistical properties of forced two-dimensional turbulence generated in two different flow domains are investigated by numerical simulations. The considered geometries are the square domain and the periodic channel domain, both bounded by lateral no-slip sidewalls. The focus is on the direct enstrophy cascade range and how the statistical properties change in the presence of no-slip boundaries. The scaling exponents of the velocity and the vorticity structure functions are compared to the classical Kraichnan-Batchelor-Leith (KBL) theory, which assumes isotropy, homogeneity, and self-similarity for turbulence scales between the forcing and dissipation scale. Our investigation reveals that in the interior of the flow domain, turbulence can be considered statistically isotropic and locally homogeneous for the enstrophy cascade range, but it is weakly intermittent. However, the scaling of the vorticity structure function indicates a steeper slope for the energy spectrum than the KBL theory predicts. Near the walls the turbulence is strongly anisotropic at all flow scales.

19.
Hum Reprod ; 26(9): 2415-24, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21708794

RESUMO

BACKGROUND: This study examines the findings from the largest survey to date of donor-inseminated (DI) offspring and focuses on respondents' learning of the method of their conception and their desire to contact their donor. METHODS: Online questionnaires were completed by 741 DI offspring, of whom 61.8% have heterosexual parents and 38.2% have lesbian parents. Respondents were recruited via the Donor Sibling Registry, a non-profit US-based international registry that facilitates communication between donor-conceived offspring and their non-biological and biological relatives. Data were collected on family composition, offspring's feelings regarding the method of their conception, communication within families, donor anonymity and their search for their donors. This investigation focuses on the relationship between family type (single or dual-parent and lesbian or heterosexual parent/s) and offspring's reactions to learning of their DI conception. RESULTS: Offspring of lesbian parents learned of their DI origins at earlier ages than offspring of heterosexual parents. In the latter families, disclosure tended to occur earlier in single-parent than in dual-parent families. Disclosure was most likely to be confusing to offspring of heterosexual parents, particularly when it occurred at an older age. The vast majority of offspring in all types of families desired contact with their donor; however, comfort in expressing curiosity regarding one's donor was lowest in dual-parent heterosexual families, with about one-quarter reporting an inability to discuss their origins with their social father. CONCLUSIONS: Although the findings are not based on a random sample, the desire among offspring surveyed here is for greater openness and contact with their donor. A variety of strategies are needed for offspring of heterosexual couples to benefit optimally from the general trend toward openness in gamete donation.


Assuntos
Revelação , Características da Família , Inseminação Artificial Heteróloga/psicologia , Relações Pais-Filho , Espermatozoides , Doadores de Tecidos/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Confusão , Feminino , Homossexualidade Feminina , Humanos , Masculino , Pais Solteiros
20.
Hum Reprod ; 26(3): 638-45, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21177310

RESUMO

BACKGROUND: This study examined the motivations and experiences of anonymous donors who decide to make themselves open to contact with their donor offspring. METHODS: Online questionnaires were completed by 63 sperm donors and 11 oocyte donors recruited via the Donor Sibling Registry (http://www.donorsiblingregistry.com/), a US-based international registry that facilitates contact between donor-conceived offspring and their donors. RESULTS: Donors' main reasons for donating were financial payment and wanting to help others. Sperm donors had donated between 1 and 950 times (median = 100) and oocyte donors had donated between 1 and 5 times (median = 2). The majority of sperm donors and more than one-third of oocyte donors expressed concerns about having donated. These concerns were mainly about the well-being of any children conceived using their gametes and not being able to make contact with them. Most sperm and oocyte donors felt that it was important to know how many offspring had been born using their donation, and 51% of sperm donors and 46% of oocyte donors wanted identifying information. All of the donors who had contact with their donor offspring reported positive experiences and the majority continued to have regular contact. CONCLUSIONS: Although the sample may not be representative of all anonymous donors, this study highlights the importance of donors having access to information about their donor offspring and the positive consequences that may arise when contact is made.


Assuntos
Inseminação Artificial Heteróloga/psicologia , Relações Interpessoais , Doação de Oócitos/psicologia , Doadores de Tecidos/psicologia , Adulto , Idoso , Envelhecimento , Atitude Frente a Saúde , Confidencialidade/psicologia , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Motivação , Sistema de Registros , Inquéritos e Questionários , Adulto Jovem
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