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111.
JD Roberts JC Herkert J Rutberg SM Nikkel ACP Wiesfeld D Dooijes RM Gow JP van Tintelen MH Gollob 《Clinical genetics》2013,83(5):452-456
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis. 相似文献
112.
Follicular density in ovarian biopsy of infertile women: a novel method to assess ovarian reserve 总被引:4,自引:15,他引:4
Lass A; Silye R; Abrams DC; Krausz T; Hovatta O; Margara R; Winston RM 《Human reproduction (Oxford, England)》1997,12(5):1028-1031
The ageing ovary appears to be characterized by depletion of primordial
follicles. The relationship between infertility and the number of follicles
in the ovarian cortex is not known. Moreover, there are no accurate markers
or clinical methods to predict the decline in ovarian reserve. This study
investigates the correlation between early follicular follicle stimulating
hormone, ovarian size and follicular density in 60 infertile women aged
19-45 years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each
patient while performing diagnostic laparoscopy (n = 28) or laparotomy for
tubal surgery or myomectomy (n = 32). The median number of follicles was
similar in tubal and unexplained infertility patients (9.5 versus 5.5).
Increasing age showed a significant negative correlation with follicular
density and ovarian volume (r = -0.46, P = 0.0003;. r = -0.43, P = 0.0016,
respectively). In women > or = 35 years of age the ovarian volume showed
a strong correlation with follicular density (r = 0.71, P < 0.0001). Our
results indicate that infertile women in their late thirties and over have
a decreased ovarian reserve which could possibly be predicted by ovarian
volume measurement. Ovarian biopsy may have a place as part of infertility
evaluation in older women.
相似文献
113.
de Oliveira CA Alexandrino F Christiani TV Steiner CE Cunha JL Guerra AT Sartorato EL 《American journal of medical genetics. Part A》2007,(14):1574-1579
Hereditary hearing loss is a complex disorder that involves a large number of genes. In developed countries, 1 in 1,000 children is born with deafness severe enough to require special education services, and about 60% of the cases of isolated deafness have a genetic origin. Although more than 100 genes for hearing loss are known currently, only a few are routinely tested in the clinical practice. In this study, we present our findings from the molecular diagnostic screening of the GJB2 and GJB3 genes, del(GJB6-D13S1,830) and del(GJB6-D13S1,854) deletions in the GJB6 gene, Q829X mutation in the otoferlin gene (OTOF) and, the A1,555G and A7,445G mutations in the mitochondrial genome over an 8-year period. Mutations analysis in the previously mentioned genes and mutations was performed on 645 unrelated Brazilian patients with hearing loss who fell into two different testing groups. Different mutations in the GJB2 gene were responsible for most of cases studied, but deletions in the GJB6 gene as well as mitochondrial mutations were also found. While most cases of hearing loss in this country are due to environmental factors, the genetic etiology of deafness will increasingly be determined as more genetic tests become available. 相似文献
114.
Monica C. O. Campos Kelly Salomão Denise B. Castro-Pinto Leonor L. Leon Helene S. Barbosa Maria Aparecida M. Maciel Solange L. de Castro 《Parasitology research》2010,107(5):1193-1204
Croton cajucara is a plant found in the Amazon region and is known for its medicinal properties. The effects of the methanolic extract of the stem bark of C. cajucara (MCC) and of the isolated terpenes, trans-dehydrocrotonin (t-DCTN) and acetyl aleuritolic acid (AAA), were investigated using four isolates of Trypanosoma cruzi. In assays with trypomastigotes, the extract was more active than the isolated compounds, presenting IC50 in the range of 10 to 50 μg/mL. The trypanocidal effect of MCC, AAA and benznidazole was significantly higher in the GLT291 and C45 strains, which were recently isolated from wild animals. MCC and AAA caused a dose-dependent inhibition of epimastigote proliferation. In assays using intracellular amastigotes, AAA and MCC reduced the percent of infection and the endocytic index after 96 h of treatment, at concentrations that were non-toxic to the host cells. MCC inhibited the trypanothione reductase pathway in both epimastigotes and trypomastigotes of all the subpopulations. The absence of AAA activity on the trypanothione reductase pathway in epimastigotes of Dm28c suggests heterogeneity of the biochemical profile between this clone and the three strains. Epimastigotes and trypomastigotes (GLT291) were treated for 24 h with MCC or AAA, and both induced alterations of the plasma membrane, while AAA-treated epimastigotes also displayed mitochondrial damage. 相似文献
115.
Futata EA de Brito CA Victor JR Fusaro AE Oliveira CR Maciel M da Silva Duarte AJ Sato MN 《Immunobiology》2006,211(3):157-166
Durable antigen (Ag)-specific T- and B-cell anergy induced by oral tolerance is an attractive strategy for immunotherapy of allergic diseases. Here, we address the lasting effect of oral tolerance induction in na?ve or primed mice to ovalbumin (OVA) on antibody production. Single feeding with OVA prior to immunization or double feeding, before and after Ag priming, in A/Sn mice, induced a long-lasting suppression of IgE, IgG1 and IgG2a responses up to 8 months after immunization. In contrast, primed-fed mice had transient IgE inhibition. Naive and double-treated mice showed marked Ag-specific unresponsiveness and scarce cytokines production. Inhibition of IL-2 and IFN-gamma secretion in na?ve-fed mice were restored in the presence of anti-CD28 mAb plus Ag stimulation. The durable inhibition of Ab production in OVA-fed mice was related to the persistent decrease of B7.2 expression on B cells. Ag feeding in naive and primed status may be a prophylactic measure to avoid later Ag sensitization. 相似文献
116.
A role for CD4+CD25+ T cells in regulation of the immune response during human tuberculosis 总被引:12,自引:0,他引:12 下载免费PDF全文
Ribeiro-Rodrigues R Resende Co T Rojas R Toossi Z Dietze R Boom WH Maciel E Hirsch CS 《Clinical and experimental immunology》2006,144(1):25-34
Active tuberculosis (TB) is associated with prolonged suppression of Mycobacterium tuberculosis (MTB)-specific immune responses, but mechanisms involved are understood incompletely. We investigated a potential role for CD4+CD25+ regulatory T cells in depressed anti-MTB immunity by evaluating serially CD4 cell phenotype and interferon (IFN)-gamma production by mononuclear cells from patients with TB. At diagnosis, frequencies of CD4+CD25+ T cells were increased in blood from TB patients compared to healthy purified protein derivative (PPD)-positive controls (with a history of prior TB exposure), and remained elevated at completion of therapy (6 months). By contrast, expression of another activation marker, CD69, by CD4 T cells was increased at diagnosis, but declined rapidly to control levels with treatment. Among CD4+CD25+ T cells from TB patients at diagnosis those expressing high levels of CD25, probably representing regulatory T cells, were increased 2.9-fold when compared to control subjects, while MTB-stimulated IFN-gamma levels in whole blood supernatants were depressed. A role for CD4+CD25+ T cells in depressed IFN-gamma production during TB was substantiated in depletion experiments, where CD25+-depleted CD4 T cells produced increased amounts of IFN-gamma upon MTB stimulation compared to unseparated T cells. At follow-up, IFN-gamma production improved most significantly in blood from TB patients with high baseline frequencies of CD4+CD25+ T cells (more than threefold higher than controls for both total and CD25hi+ CD4 T cells), who also had a significant drop in frequencies of both total and 'regulatory' CD4+CD25+ T cells in response to treatment. Expansion of CD4+CD25+ regulatory T cells during active TB may play a role in depressed T cell IFN-gamma production. 相似文献
117.
Naira R. Maciel Priscila G. Reis Kelly C. Kato Alessandra T. Vidal Homero N. Guimarães Frederic Frézard Neila M. Silva-Barcellos Andrea Grabe-Guimarães 《Toxicology letters》2010
Trivalent antimonial drugs, including tartar emetic (TA), are known to induce important cardiotoxicity observed by electrocardiographic abnormalities. Liposome encapsulation was found to reduce the overall acute toxicity of TA. The present work investigated the cardiovascular parameters alterations of rats submitted to the treatment with free and encapsulated TA in long-circulating liposomes. Liposomes were made using lipids DSPC, DSPE-PEG and cholesterol. The cardiovascular signals, electrocardiogram (ECG) and arterial blood pressure (AP), were recorded from anaesthetized Wistar rats after intravenous (IV) administration of a single specially high dose (17 mg/kg) of TA in liposomes and in free form. The IV administration of TA solution caused significant increase of QT interval of ECG and significant reduction of AP when compared to the control group. These alterations were not observed when liposomes TA were administered and the profile of ECG and AP data was quite similar to the control groups. In conclusion, a liposomal formulation of TA showed a reduced cardiotoxic profile for TA when compared to the free form. 相似文献
118.
Objective
to review the literature around what is considered to be a good midwife and in particular what women value in a midwife, in order to identify the gaps in the evidence for future research.Design
this paper reviews the research in the area of interest over the past 30 years. The literature search focused on the concept of good midwife using synonyms and antonyms. The inclusion criteria included language (English or Italian). The examined databases were Medline, Maternity and Infant Care, Applied Social Sciences Index and Abstract and CINAHL.Setting
studies conducted in high-income countries were taken into account. A focused review of papers which explicitly investigated what a good midwife means and a thematic analysis on what women value in a midwife were carried out.Participants
different standpoints have been considered (midwives, student midwives, women and their partners), focusing in particular on women viewpoint.Findings
the literature review reveals information about what is considered to be a good midwife from a range of perspectives and what women value in a midwife. A good midwife should possess several attributes: theoretical knowledge, professional competencies, personal qualities, communication skills and moral/ethical values. According to the thematic analysis around what childbearing women value in a midwife, frequent key-themes emerging from the literature were: support, possibility of choice, feeling in control and having appropriate information.Key conclusions
the meaning of good midwife might change according to different actors involved in midwifery care and there is no agreement on the definition of what constitutes a good midwife. Furthermore, it is not clear if what women value in a good midwife corresponds to the midwives' perception of themselves as good professionals. There is a dearth of information around women's expectations and experiences specifically of a good midwife, and even less around whether this changes according to where they give birth.Implications for practice
this literature review seeks to stimulate debate and reflection among midwives and professionals involved in the childbearing event, in order to fulfil women's expectations of their midwife and increase their satisfaction with the birth experience. The identification of the gaps in the evidence provided the starting point and allowed the development of research questions and methodology for an ongoing doctoral research. On the basis of the gaps in the evidence, the doctoral research will explore and seek to explain nulliparous women's expectations and experiences of a good midwife in the context of different planned place of birth, using a Grounded Theory methodology. It is also expected that the findings of this literature review will stimulate additional research in this area to ultimately inform midwifery practice and midwifery educational programmes. 相似文献119.
120.