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81.
Priapism, although uncommon in the general population, is one of the many serious complications associated with sickle cell disease (SCD). Few studies have described the clinical and hematologic characteristics of individuals with priapism and SCD. Using data from the Cooperative Study for Sickle Cell Disease, we assembled 273 case subjects with priapism and 979 control subjects. Case subjects, compared with control subjects, had significantly lower levels of hemoglobin; higher levels of lactate dehydrogenase, bilirubin, and aspartate aminotransferase; and higher reticulocyte, white blood cell, and platelet counts. These findings suggest an association of priapism with increased hemolysis. Hemolysis decreases the availability of circulating nitric oxide, which plays an important role in erectile function. 相似文献
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Christopher D. Carey Daniel Gusenleitner Bjoern Chapuy Alexandra E. Kovach Michael J. Kluk Heather H. Sun Rachel E. Crossland Chris M. Bacon Vikki Rand Paola Dal Cin Long P. Le Donna Neuberg Aliyah R. Sohani Margaret A. Shipp Stefano Monti Scott J. Rodig 《The Journal of molecular diagnostics : JMD》2015,17(1):19-30
86.
Glucose and Metformin Modulate Human First Trimester Trophoblast Function: a Model and Potential Therapy for Diabetes‐Associated Uteroplacental Insufficiency
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87.
Braden S. Jensen Tobias Willer Dimah N. Saade Mary O. Cox Tahseen Mozaffar Mena Scavina Vikki A. Stefans Thomas L. Winder Kevin P. Campbell Steven A. Moore Katherine D. Mathews 《Human mutation》2015,36(12):1159-1163
Mutations in GDP‐mannose pyrophosphorylase B (GMPPB), a catalyst for the formation of the sugar donor GDP‐mannose, were recently identified as a cause of muscular dystrophy resulting from abnormal glycosylation of α‐dystroglycan. In this series, we report nine unrelated individuals with GMPPB‐associated dystroglycanopathy. The most mildly affected subject has normal strength at 25 years, whereas three severely affected children presented in infancy with intellectual disability and epilepsy. Muscle biopsies of all subjects are dystrophic with abnormal immunostaining for glycosylated α‐dystroglycan. This cohort, together with previously published cases, allows preliminary genotype–phenotype correlations to be made for the emerging GMPPB common variants c.79G>C (p.D27H) and c.860G>A (p.R287Q). We observe that c.79G>C (p.D27H) is associated with a mild limb‐girdle muscular dystrophy phenotype, whereas c.860G>A (p.R287Q) is associated with a relatively severe congenital muscular dystrophy typically involving brain development. Sixty‐six percent of GMPPB families to date have one of these common variants. 相似文献
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Ma Y Mor G Abrahams VM Buhimschi IA Buhimschi CS Guller S 《American journal of reproductive immunology (New York, N.Y. : 1989)》2006,55(1):12-18
PROBLEM: The placental syncytium is a differentiated cell type on the surface of the villus that has the potential to release cytokines directly to maternal blood. Responsiveness of this cell type to inflammatory compounds remains largely unelucidated. METHOD OF STUDY: Response to a pro-inflammatory (lipopolysaccharide, LPS) and an anti-inflammatory (dexamethasone, DEX) compound was studied in primary cultures of syncytiotrophoblasts (SCTs). Cells were incubated with and without LPS and DEX. Cytokine levels in conditioned media were determined by enzyme-linked immunosorbent assay and proteome arrays. RESULTS: LPS treatment induced a fourfold increase in interleukin-8 (IL-8) levels in SCTs. LPS enhanced the expression of both pro- and anti-inflammatory cytokines in SCTs. DEX treatment reduced IL-8 levels in control and LPS-treated cultures by 70-90%. CONCLUSION: Cytokine expression in SCTs was enhanced by LPS treatment and this effect was suppressed by glucocorticoid treatment. This suggests that inflammatory compounds may alter cytokine expression in the syncytium throughout gestation. 相似文献
89.
Heparin prevents programmed cell death in human trophoblast 总被引:3,自引:0,他引:3
Hills FA Abrahams VM González-Timón B Francis J Cloke B Hinkson L Rai R Mor G Regan L Sullivan M Lam EW Brosens JJ 《Molecular human reproduction》2006,12(4):237-243
Heparin is used clinically for the prevention of pregnancy complications associated with prothrombotic disorders, especially antiphospholipid antibody syndrome. Recent studies have suggested that heparin may exert direct effects on placental trophoblast, independently of its anticoagulant activity. We now demonstrate that heparin abrogates apoptosis of primary first trimester villous trophoblast in response to treatment with the pro-inflammatory cytokines interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. This multifunctional glycosaminoglycan also inhibited apoptosis induced by other agents, including staurosporin, broad-spectrum kinase inhibitor and thrombin. Furthermore, heparin attenuated caspase-3 activity, a hallmark of apoptosis, in human first trimester villous and extravillous trophoblast cell lines treated with peptidoglycan, a Toll-like receptor-2 agonist isolated from Staphylococcus aureus. The ability of heparin to antagonize cell death induced by such diverse apoptotic signals suggested that it acts as a survival factor for human trophoblast. We demonstrate that heparin, like epidermal growth factor (EGF) and heparin-binding EGF (HB-EGF), elicits phosphorylation of the EGF receptor and activation of the phosphatidyl inositol 3-kinase (PI3K)-, the extracellular signal-related kinase 1/2 (ERK1/2)- and the c-Jun NH2 terminal kinase (JNK)-signal transduction pathways in primary villous trophoblast. In summary, we have demonstrated that heparin activates multiple anti-apoptotic pathways in human trophoblast. Our results suggest that heparin may be useful in the management of at-risk patients, even in the absence of an identifiable thrombophilic disorder. 相似文献
90.
Abrahams VM Schaefer TM Fahey JV Visintin I Wright JA Aldo PB Romero R Wira CR Mor G 《Human reproduction (Oxford, England)》2006,21(9):2432-2439
BACKGROUND: During pregnancy, the placenta may become exposed to micro-organisms, such as viruses, which may pose a substantial threat to the embryo/fetus well-being. Recent insight into the immunological capabilities of the trophoblast suggests that the placenta may function as an active barrier by recognizing and responding to pathogens through Toll-like receptors (TLRs). METHODS: The objective of this study was to determine whether the engagement of TLR-3 with viral dsRNA by first-trimester trophoblast could induce the production of factors necessary to generate an antiviral response. Therefore, trophoblast cells were exposed to the TLR-3 agonist, Poly(I : C). RESULTS: We report that following stimulation with Poly(I : C), first-trimester trophoblast cells produce interferon beta (IFNbeta) and secretory leukocyte protease inhibitor (SLPI), as well as the intracellular factors 2',5'-oligoadenylate synthetase (OAS), Myxovirus-resistance A (MxA) and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G). This response is TLR-3 specific because the TLR-4 ligand, lipopolysaccharide (LPS), had no effect on the production of these antimicrobial factors. Furthermore, we describe a positive feedback mechanism in which IFNbeta enhances the antiviral response by promoting the production of OAS, MxA and APOBEC3G. CONCLUSIONS: These findings suggest that trophoblast cells are able to recognize and specifically respond to viral products in a highly regulated fashion and that the placenta may be pivotal in the control of viral infections at the maternal-fetal interface. 相似文献