RESUMEN
This case report describes a novel mutation of the SPTB gene as a potential pathogenic cause of spherocytosis. A 3-week-old male presented with clinical and laboratory signs consistent with hemolytic spherocytosis, including jaundice, hyperbilirubinemia, anemia, reticulocytosis, negative Coombs test, no ABO or Rh incompatibility, and a peripheral blood smear notable for numerous spherocytes. His laboratory work demonstrated persistent anemia despite daily folate prompting next-generation sequencing which revealed a novel mutation in the SPTB gene resulting in a nonfunctioning protein product. Correlation of the genetic finding with clinical presentation may help guide management for this and future patients.
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Secuenciación de Nucleótidos de Alto Rendimiento , Hiperbilirrubinemia , Recién Nacido , Humanos , Masculino , Heterocigoto , MutaciónRESUMEN
PURPOSE: In this study, we evaluated the risk behaviors that are drivers of the HIV epidemic among adolescent girls and young women in Zambia using a focus group research technique. SUBJECTS AND METHODS: Eighteen adolescent couples (n=18 females and 18 males) aged 16-24 participated in six focus groups discussions (3 per gender) convened at three health facilities in Lusaka, Zambia. Focus group moderators utilized a set of open-ended questions to guide the 60-minute sessions. The focus group audio recordings were transcribed, coded, and analyzed using qualitative content analysis in Nvivo 11. RESULTS: Three themes and four subthemes were identified relating to adolescent and young adult couples' knowledge, views, and male partner attitudes toward intravaginal practices (IVPs). The first theme, knowledge and rationale for IVPs, consisted of the subthemes relating to why adolescents and young adult couples engage in IVPs and assessed their knowledge of health risks associated with IVPs. The second theme, attitudes toward IVPs, consisted of the subtheme willingness to stop or support partner to discontinue IVP and practices toward IVP and strategies for changing. The third theme, strategies for changing IVPs, consisted of the subtheme raise awareness. CONCLUSION: IVPs used for cleaning purposes were perceived as essential to enhancing hygiene, health, and sexual satisfaction for both girls and boys. However, couples expressed concern about the health effects of IVPs used for tightening and a desire for learning more about this practice as well as stopping it.
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BACKGROUND: Ag-dependent activation of IgE-bearing mast cells is a critical first step in immediate hypersensitivity and other allergic responses. Recent studies have revealed Ag-independent effects of monoclonal mouse IgE molecules on mast cell survival and activation. However, no studies have been performed on the effects of polyclonal IgE molecules. Here, we tested whether polyclonal mouse and human IgE molecules affect survival and cytokine production in mast cells. METHODS: Mast cells were cultured in the presence of polyclonal mouse and human IgE molecules, and cell survival and cytokine production were analyzed. RESULTS: Polyclonal mouse IgE molecules in sera from mice with atopic dermatitis-like allergic skin inflammation, enhanced survival and cytokine production in mast cell cultures. Similar to the effects of monoclonal IgE, the polyclonal IgE effects were mediated by the high-affinity IgE receptor, FcepsilonRI. Human polyclonal IgE molecules present in sera from atopic dermatitis patients were also capable of activating mast cells, and inducing IL-8 production in human cord blood-derived mast cells. CONCLUSIONS: These results imply that polyclonal IgE in atopic dermatitis and other atopic conditions might modulate mast cell number and function, thus amplifying the allergic response.
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Citocinas/biosíntesis , Dermatitis Atópica/inmunología , Inmunoglobulina E/inmunología , Mastocitos/inmunología , Animales , Células de la Médula Ósea , Supervivencia Celular/inmunología , Células Cultivadas , Sangre Fetal/inmunología , Humanos , Ratones , Ratones Endogámicos C57BL , Receptores de IgE/genética , Receptores de IgE/inmunologíaRESUMEN
Studies performed using cultured cells indicate that IgE functions not only to trigger degranulation of mast cells following allergen exposure, but also to enhance their survival. Such an influence of IgE on mast cell homeostasis during allergic responses in vivo has not been established. In this study, we show that inhalation of Aspergillus fumigatus extract in mice induced a dramatic rise in IgE accompanied by an increase in airway mast cells. These had an activated phenotype with high levels of FcepsilonRI. Plasma mast cell protease-1 was also increased, indicating an elevated systemic mast cell load. In addition, enhanced levels of IL-5 and eosinophils were observed in the airway. Both mast cell expansion and activation were markedly attenuated in IgE(-/-) animals that are incapable of producing IgE in response to A. fumigatus. The recruitment of eosinophils to the airways was also reduced in IgE(-/-) mice. Analyses of potential cellular targets of IgE revealed that IgE Abs are not required for the induction of mast cell progenitors in response to allergen, but rather act by sustaining the survival of mature mast cells. Our results identify an important role for IgE Abs in promoting mast cell expansion during allergic responses in vivo.
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Hipersensibilidad/inmunología , Inmunoglobulina E/inmunología , Mastocitos/inmunología , Neumonía/inmunología , Células Madre/inmunología , Traslado Adoptivo , Animales , Aspergillus fumigatus/inmunología , Quimiotaxis de Leucocito/inmunología , Quimasas/inmunología , Quimasas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Eosinófilos/inmunología , Citometría de Flujo , Homeostasis/inmunología , Hipersensibilidad/metabolismo , Interleucina-5/inmunología , Interleucina-5/metabolismo , Mastocitos/metabolismo , Ratones , Neumonía/metabolismo , Reacción en Cadena de la Polimerasa , Receptores de IgE/inmunología , Receptores de IgE/metabolismo , Células Madre/metabolismoRESUMEN
Gonadotropin-releasing hormone (GnRH) neurons migrate from the vomeronasal organ (VNO) in the nasal compartment to the basal forebrain in mice, beginning on embryonic day 11 (E11). These neurons use vomeronasal axons as guides to migrate through the nasal mesenchyme. Most GnRH neurons then migrate along the caudal branch of the vomeronasal nerve to reach the hypothalamus. We show here that stromal cell-derived factor-1 [SDF-1, also known as chemokine C-X-C motif ligand 12 (CXCL12)] is expressed in the embryonic nasal mesenchyme from as early as E10 in an increasing rostral to caudal gradient that is most intense at the border of the nasal mesenchyme and the telencephalon. Chemokine C-X-C motif receptor 4 (CXCR4), the receptor for SDF-1, is expressed by neurons in the olfactory epithelium and VNO. Cells derived from these sensory epithelia, including migrating GnRH neurons and ensheathing glial precursors of the migrating mass (MM), also express CXCR4, suggesting that they may use SDF-1 as a chemokine. In support of this, most GnRH neurons of CXCR4-/- mice fail to exit the VNO at E13, and comparatively few GnRH neurons reach the forebrain. There is also a significant decrease in the total number of GnRH neurons in CXCR4-/- mice and an increase in cell death within the VNO relative to controls. The MM is smaller in CXCR4-/- mice, suggesting that some MM cells also require SDF-1/CXCR4 function for migration and survival.