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1.
Biochem Biophys Res Commun ; 517(4): 755-761, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31402117

RESUMO

Ras proteins are highly conserved small GTPases in eukaryotes. GTP-bound Ras binds to effectors to trigger signaling cascades. In order to understand how extensive is the functional homology between the highly homologous proteins, S. cerevisiae Ras2 and C. albicans Ras1, we examined whether ScRas2 could functionally complement CaRas1 in activating hyphal morphogenesis as well as GPI anchor biosynthesis. We show that ScRas2 functionally complements CaRas1 in rescuing growth as well as activating hyphal growth, a process that involves plasma membrane localized Ras activating cAMP/PKA signaling via Cyr1. However, ScRas2 is unable to activate the GPI-N-acetylglucosaminyl transferase (GPI-GnT) which catalyzes the first step of GPI biosynthesis. That CaRas1 alone activates GPI-GnT and not ScRas2 suggests that this process is cAMP independent. Interestingly, CaRas1 transcriptionally activates CaGPI2, encoding a GPI-GnT subunit that has been shown to interact with CaRas1 physically. In turn, CaGPI2 downregulates CaGPI19, encoding another GPI-GnT subunit. This has direct consequences for expression of CaERG11, encoding the target of azole antifungals. This effect too is specific to CaRas1 and ScRas2 is unable to replicate it.

3.
J Assist Reprod Genet ; 36(4): 621-628, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30645703

RESUMO

PURPOSE: In vitro fertilization with trophectoderm embryo biopsy and pre-implantation genetic screening with comprehensive chromosomal screening (PGS-CCS) for aneuploidy is becoming increasingly more popular. Embryos are cryopreserved and implanted in a subsequent frozen thawed embryo transfer cycle (FET). No studies have investigated differences in pregnancy outcomes by timing of trophectoderm biopsy relative to stages of blastocyst development. METHODS: Retrospective study of all patients (n = 363) at a single IVF center between January 1, 2013 and December 31, 2016 undergoing single embryo transfer with PGS-CCS where embryos were cryopreserved with subsequent FET. Embryo expansion and grading was assessed both at the time of biopsy and transfer. Pregnancy rates were analyzed by embryo expansion and embryo grading. RESULTS: Implantation, clinical pregnancy, and live birth rates improved significantly with increased embryo expansion at the time of embryo biopsy (P < 0.001). Pregnancy loss decreased with increases in embryo expansion prior to biopsy (P < 0.001). Superior live birth rates with PGS-CCS were seen when embryos were hatching at the time of biopsy (p < 0.001). For fresh and frozen embryo transfers without PGS-CCS, embryo expansion did not affect pregnancy outcomes. CONCLUSIONS: PGS-CCS significantly increases implantation and live birth rates only if embryos are hatching at the time of biopsy. The embryo biopsy itself on a non-hatching embryo significantly damages the embryo in ways which are not reflected in future embryo expansion. IVF labs should wait until embryos hatch before performing trophectoderm biopsy.


Assuntos
Biópsia/métodos , Testes Genéticos/métodos , Diagnóstico Pré-Implantação/métodos , Aborto Espontâneo/diagnóstico , Aborto Espontâneo/fisiopatologia , Adulto , Aneuploidia , Coeficiente de Natalidade , Blastocisto/metabolismo , Criopreservação , Ectoderma/diagnóstico por imagem , Ectoderma/patologia , Implantação do Embrião/fisiologia , Desenvolvimento Embrionário/genética , Feminino , Fertilização In Vitro , Humanos , Gravidez , Resultado da Gravidez , Transferência de Embrião Único
4.
Rev. colomb. biotecnol ; 20(2): 6-18, jul.-dic. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-985440

RESUMO

ABSTRACT Biofertilizers have become an effective, eco-friendly and low cost alternative to chemical fertilizers. Process engineering and cost models for a biofertilizer plant with a production capacity of 44 tons of liquid biofertilizer per year (568 kg/batch) were developed. The models were obtained using process simulator (SuperPro Designer®), version 8.5 (Intelligen, 2012), while the 3D conceptual design and layout of the biofertilizer plant was developed with (OptiPlant®) software (ASD Global, 201 5). The total capital investment required to erect the plant is $ 3 975 000, the unit production cost of one 1.5 L bottle of liquid biofertilizer is $ 24.009, while the economic indicators Net Present Value (NPV) and Internal Rate of Return (IRR) had values of $ 716 000 and 2.55%, respectively. Also, the total revenues are $ 985 000/year, the Return on Investment (ROI) is 14.93 %, and the payback time is 6.70 years.


RESUMEN Los biofertilizantes se han convertido en una alternativa de bajo costo, efectiva y amigable con el medio ambiente en comparación con los fertilizantes químicos. En el presente trabajo se desarrollaron los modelos de ingeniería de proceso y costo de una planta de biofertilizantes líquidos con una capacidad de 44 toneladas por año (568 kg/lote). Los modelos fueron obtenidos empleando el simulador de procesos SuperPro Designer® versión 8.5 (Intelligen, 2012), mientras que el diseño conceptual en 3D y dimensionamiento de la planta se desarrolló mediante el software OptiPlant (ASD Global, 2015). Se requiere una inversión total de USD $ 3 975 000 para erigir la planta, el costo de producción unitario de una botella de 1,5 L de biofertilizantes líquido es de USD $ 24,009, mientras que los indicadores económicos Valor Actual Neto (VAN) y Tasa Interna de Retorno (TIR) tuvieron valores de USD $ 716 000 y 2,55 %, respectivamente. También se obtienen ganancias totales de USD $ 985 000/año y un valor del Período de Retorno de la Inversión de 6,70 años.

5.
Infect Immun ; 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30455194

RESUMO

Macrophages are important orchestrators of inflammation during bacterial infection acting both as effector cells and as regulators of neutrophil recruitment and life span. Differently activated macrophage populations with distinct inflammatory and microbicidal potential have been described. Our previous work unveiled a positive and a negative correlation between levels of IFN-γ and IL-17A, respectively, and lung function in cystic fibrosis, particularly in patients chronically infected with P. aeruginosa This study sought to define key parameters in human anti-bacterial immunity under Th1- and Th17-dominated inflammatory conditions; the final aim was to identify unique characteristics that could be fine-tuned therapeutically to minimise tissue damage while maximising bacterial clearance. Towards this aim neutrophils were incorporated into cultures of macrophages treated with IFN-γ or IL-17A and infected with P. aeruginosa The intent of this design was to model (i) initiation of inflammation by infected macrophages and (ii) delayed arrival of neutrophils and their exposure to macrophage-derived cytokines. Under these conditions IFN-γ decreased bacterial killing and promoted production of the monocyte chemoattractant MCP-1. In contrast, IL-17A promoted bacterial killing but did not affect MCP-1 production. Secretion of the pyrogen IL-1ß was significantly lower in the presence of IFN-γ compared to IL-17A and correlated with levels of IL1B transcript in infected macrophages. These findings support the validity of this model to investigate human anti-bacterial immunity. Based on these observations, the protective and damaging roles of IFN-γ and IL-17A, respectively, during P. aeruginosa infection could be caused by their contrasting effects on IL-1ß and MCP-1 production.

6.
J Biol Chem ; 293(31): 12222-12238, 2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-29907567

RESUMO

The ability of Candida albicans to switch between yeast to hyphal form is a property that is primarily associated with the invasion and virulence of this human pathogenic fungus. Several glycosylphosphatidylinositol (GPI)-anchored proteins are expressed only during hyphal morphogenesis. One of the major pathways that controls hyphal morphogenesis is the Ras-signaling pathway. We examine the cross-talk between GPI anchor biosynthesis and Ras signaling in C. albicans. We show that the first step of GPI biosynthesis is activated by Ras in C. albicans This is diametrically opposite to what is reported in Saccharomyces cerevisiae Of the two C. albicans Ras proteins, CaRas1 alone activates GPI-GnT activity; activity is further stimulated by constitutively activated CaRas1. CaRas1 localized to the cytoplasm or endoplasmic reticulum (ER) is sufficient for GPI-GnT activation. Of the six subunits of the GPI-N-acetylglucosaminyltransferase (GPI-GnT) that catalyze the first step of GPI biosynthesis, CaGpi2 is the key player involved in activating Ras signaling and hyphal morphogenesis. Activation of Ras signaling is independent of the catalytic competence of GPI-GnT. This too is unlike what is observed in S. cerevisiae where multiple subunits were identified as inhibiting Ras2. Fluorescence resonance energy transfer (FRET) studies indicate a specific physical interaction between CaRas1 and CaGpi2 in the ER, which would explain the ability of CaRas1 to activate GPI-GnT. CaGpi2, in turn, promotes activation of the Ras-signaling pathway and hyphal morphogenesis. The Cagpi2 mutant is also more susceptible to macrophage-mediated killing, and macrophage cells show better survival when co-cultured with Cagpi2.

7.
Obstet Gynecol ; 131(2): 364-369, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29324612

RESUMO

OBJECTIVE: To compare pertussis antibody concentrations in maternal venous serum (at the time of delivery) and umbilical cord arterial serum among women vaccinated with the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine from either 27-30 6/7 weeks of gestation or from 31-35 6/7 weeks of gestation. METHODS: We conducted a prospective cohort study of pregnant women divided into two groups based on when Tdap was administered: 27-30 6/7 weeks of gestation and 31-35 6/7 weeks of gestation. Paired maternal and umbilical cord samples were obtained at the time of delivery to determine immunoglobulin G (IgG) concentrations to pertussis toxin and pertactin. RESULTS: Eighty-eight pregnant women were enrolled. Cord serum pertussis toxin IgG concentrations were approximately twice maternal serum pertussis toxin IgG concentrations (91.6 vs 48.6 enzyme-linked immunoassay [ELISA] units/mL, P<.01) and were significantly correlated (Pearson correlation coefficient=0.85, P<.01). There was no significant difference in maternal serum pertussis toxin IgG concentrations (48.6 vs 48.6 ELISA units/mL, P=.99), cord serum pertussis toxin IgG concentrations (92.1 vs 90.7 ELISA units/mL, P=.95), and cord serum pertactin IgG concentrations (798 vs 730 international units/mL, P=.73) between the two groups. Furthermore, there was no correlation between time from vaccination to delivery and these three parameters. Cord serum pertussis toxin IgG concentrations were greater than 10 ELISA units/mL (ie, in the protective range) in 87% and 97% of those vaccinated from 27-30 6/7 weeks of gestation and from 31-35 6/7 weeks of gestation, respectively (P=.13). CONCLUSION: Maternal vaccination against pertussis between 27 and 36 weeks of gestation was associated with a high percentage of newborns with antibody concentrations conferring protection and did not vary by gestational age at vaccination.


Assuntos
Anticorpos Antibacterianos/sangue , Bordetella pertussis/imunologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular , Terceiro Trimestre da Gravidez , Vacinação , Feminino , Sangue Fetal , Humanos , Recém-Nascido , Gravidez , Coqueluche/prevenção & controle
8.
Adv Healthc Mater ; 6(21)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28782184

RESUMO

Adverse immune reactions prevent clinical translation of numerous implantable devices and materials. Although inflammation is an essential part of tissue regeneration, chronic inflammation ultimately leads to implant failure. In particular, macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. Here, this paper demonstrates that macrophage polarity within biomaterials can be controlled through integrin-mediated interactions between human monocytic THP-1 cells and collagen-derived matrix. Surface marker, gene expression, biochemical, and cytokine profiling consistently indicate that THP-1 cells within a biomaterial lacking cell attachment motifs yield proinflammatory M1 macrophages, whereas biomaterials with attachment sites in the presence of interleukin-4 (IL-4) induce an anti-inflammatory M2-like phenotype and propagate the effect of IL-4 in induction of M2-like macrophages. Importantly, integrin α2ß1 plays a pivotal role as its inhibition blocks the induction of M2 macrophages. The influence of the microenvironment of the biomaterial over macrophage polarity is further confirmed by its ability to modulate the effect of IL-4 and lipopolysaccharide, which are potent inducers of M2 or M1 phenotypes, respectively. Thus, this study represents a novel, versatile, and effective strategy to steer macrophage polarity through integrin-mediated 3D microenvironment for biomaterial-based programming.


Assuntos
Materiais Biocompatíveis/química , Hidrogéis/química , Integrina alfa2beta1/metabolismo , Antígeno B7-2/metabolismo , Materiais Biocompatíveis/farmacologia , Biomarcadores/metabolismo , Linhagem Celular , Polaridade Celular/efeitos dos fármacos , Microambiente Celular/efeitos dos fármacos , Força Compressiva , Citocinas/metabolismo , Citoesqueleto/efeitos dos fármacos , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-4/química , Interleucina-4/metabolismo , Lectinas Tipo C/metabolismo , Ligantes , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Lectinas de Ligação a Manose/metabolismo , Microscopia Confocal , Receptores de Superfície Celular/metabolismo , Vinculina/genética , Vinculina/metabolismo
9.
J Assist Reprod Genet ; 34(10): 1333-1340, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28639180

RESUMO

PURPOSE: Few published articles have compared initial hCG values across all different types of ART cycles, including cycles with fresh or frozen embryo transfer. No articles have compared initial hCG values in cycles utilizing preimplantation genetic screening (PGS). The purpose of this study is to compare initial hCG values after fresh embryo transfer, frozen embryo transfer, and after PGS. METHODS: This was a single-center retrospective cohort study at an academically affiliated private IVF center. All fresh and frozen embryo transfers between January 2013 and December 31, 2015 were included. We compared mean initial serum hCG values 14 days after oocyte retrieval for fresh cycles and 9 days after frozen embryo transfer. We examined cycles of single embryo transfer (SET) and double embryo transfer (DET). RESULTS: Two hundred elven IVF (fresh embryo transfer), 128 FET (frozen embryo transfer cycles, no PGS), and 111 PGS cycles (ovarian stimulation with embryo cryopreservation, PGS, and frozen transfer in a subsequent estrogen-primed cycle) with initial positive hCG values were analyzed. In patients achieving a positive hCG after SET, initial hCG values were higher after PGS compared to FET (182.4 versus 124.0 mIU/mL, p = 0.02) and IVF (182.4 versus 87.1 mIU/mL, p < 0.001) as well as FET compared to IVF (124.0 versus 87.1 mIU/mL, p < 0.01). After DET, initial hCG values were higher after PGS (222.8 mIU/mL) compared to FET (182.1 mIU/mL, p = 0.02) and IVF (131.1 mIU/mL, p = 0.001). CONCLUSIONS: Our study suggests that initial serum hCG values are higher after using PGS and higher after the transfer of a frozen embryo compared to a fresh embryo. This suggests that initial hCG values relate to the chromosomal status of embryos. Initial hCG values may help determine intervention and monitoring later in pregnancy.


Assuntos
Gonadotropina Coriônica/sangue , Transferência Embrionária/métodos , Diagnóstico Pré-Implantação/métodos , Adulto , Criopreservação/métodos , Feminino , Fertilização In Vitro/métodos , Humanos , Recuperação de Oócitos , Indução da Ovulação , Gravidez , Estudos Retrospectivos
10.
Immunobiology ; 221(11): 1237-46, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27349596

RESUMO

Macrophages are innate immune cells that have a central role in combating infection and maintaining tissue homeostasis. They exhibit remarkable plasticity in response to environmental cues. At either end of a broad activation spectrum are pro-inflammatory (M1) and anti-inflammatory (M2) macrophages with distinct functional and phenotypical characteristics. Macrophages also play a crucial role in orchestrating immune responses to biomaterials used in the fabrication of implantable devices and drug delivery systems. To assess the impact of different surface chemistries on macrophage polarisation, human monocytes were cultured for 6 days on untreated hydrophobic polystyrene (PS) and hydrophilic O2 plasma-etched polystyrene (O2-PS40) surfaces. Our data clearly show that monocytes cultured on the hydrophilic O2-PS40 surface are polarised towards an M1-like phenotype, as evidenced by significantly higher expression of the pro-inflammatory transcription factors STAT1 and IRF5. By comparison, monocytes cultured on the hydrophobic PS surface exhibited an M2-like phenotype with high expression of mannose receptor (MR) and production of the anti-inflammatory cytokines IL-10 and CCL18. While the molecular basis of such different patterns of cell differentiation is yet to be fully elucidated, we hypothesise that it is due to the adsorption of different biomolecules on these surface chemistries. Indeed our surface characterisation data show quantitative and qualitative differences between the protein layers on the O2-PS40 surface compared to PS surface which could be responsible for the observed differential macrophage polarisation on each surface.


Assuntos
Adesão Celular/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Propriedades de Superfície , Adesão Celular/genética , Diferenciação Celular/imunologia , Células Cultivadas , Citocinas/biossíntese , Expressão Gênica , Humanos , Interações Hidrofóbicas e Hidrofílicas , Mediadores da Inflamação/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Complexo Antígeno L1 Leucocitário/genética , Complexo Antígeno L1 Leucocitário/metabolismo , Ativação de Macrófagos/genética , Macrófagos/citologia , Lectinas de Ligação a Manose/genética , Lectinas de Ligação a Manose/metabolismo , Monócitos/citologia , Monócitos/imunologia , Monócitos/metabolismo , Poliestirenos/química , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo
11.
Biomacromolecules ; 17(6): 2189-98, 2016 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-27183396

RESUMO

This study aims to design an optimal polyelectrolyte multilayer film of poly-l-lysine (PLL) and hyaluronic acid (HA) as an anti-inflammatory cytokine release system in order to decrease the implant failure due to any immune reactions. The chemical modification of the HA with aldehyde moieties allows self-cross-linking of the film and an improvement in the mechanical properties of the film. The cross-linking of the film and the release of immunomodulatory cytokine (IL-4) stimulate the differentiation of primary human monocytes seeded on the films into pro-healing macrophages phenotype. This induces the production of anti-inflammatory cytokines (IL1-RA and CCL18) and the decrease of pro-inflammatory cytokines secreted (IL-12, TNF-α, and IL-1ß). Moreover, we demonstrate that cross-linking PLL/HA film using HA-aldehyde is already effective by itself to limit inflammatory processes. Finally, this functionalized self-cross-linked PLL/HA-aldehyde films constitutes an innovative and efficient candidate for immunomodulation of any kind of implants of various architecture and properties.


Assuntos
Reagentes para Ligações Cruzadas/química , Citocinas/administração & dosagem , Ácido Hialurônico/química , Imunomodulação/efeitos dos fármacos , Inflamação/tratamento farmacológico , Polieletrólitos/química , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/química , Humanos , Inflamação/imunologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Propriedades de Superfície
12.
Taiwan J Ophthalmol ; 6(4): 206-209, 2016 Oct-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29018745

RESUMO

Treacher Collins syndrome is a congenital disorder with bilaterally symmetric anomalies of the structures developing from the first and second branchial arches. The ocular and orbital features are an obligatory component for the diagnosis. We presented a case of typical, complete syndrome and also reviewed the varied ophthalmological manifestations of the disease in the literature. Antimongoloid slanting of palpebral fissures and lower lid colobomas are constant features of the syndrome. However, varied ocular and lacrimal drainage anomalies are also associated. TCS is a syndrome with multiple ocular and orbital features, a knowledge of which will help in the diagnosis of incomplete forms of the syndrome.

13.
PLoS One ; 10(2): e0117447, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25706389

RESUMO

Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF) patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN)-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1) and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human macrophages infected with P. aeruginosa: untreated < treated with GM-CSF < treated with IFN-γ < treated with GM-CSF and IFN-γ.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Interferon gama/metabolismo , Macrófagos/metabolismo , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/fisiologia , Adolescente , Adulto , Fibrose Cística/metabolismo , Fibrose Cística/microbiologia , Citocinas/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Macrófagos/microbiologia , Masculino , Pseudomonas aeruginosa/crescimento & desenvolvimento , Adulto Jovem
14.
J Biol Chem ; 286(15): 13033-40, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21335554

RESUMO

Dendritic cells are professional antigen-presenting cells that are specialized in antigen uptake and presentation. Allergy to cat has increased substantially in recent years and has been shown to be positively associated with asthma. We have recently shown that the mannose receptor (MR), a C-type lectin expressed by dendritic cells, recognizes various glycoallergens from diverse sources and is involved in promoting allergic responses to a major house dust mite allergen in vitro. Here we investigated the potential role of MR in allergic responses to Fel d 1, a major cat allergen. Fel d 1 binding to MR was confirmed by ELISA. Using blocking, gene silencing (siRNA) experiments, and MR knock-out (MR(-/-)) cells, we have demonstrated that MR plays a major role in internalization of Fel d 1 by human and mouse antigen-presenting cells. Intriguingly, unlike other glycoallergens, recognition of Fel d 1 by MR is mediated by the cysteine-rich domain, which correlates with the presence of sulfated carbohydrates in natural Fel d 1. WT and MR(-/-) mice were used to study the role of MR in allergic sensitization to Fel d 1 in vivo. MR(-/-) mice sensitized with cat dander extract and Fel d 1 produced significantly lower levels of total IgE, Fel d 1-specific-IgE and IgG1, the hallmarks of allergic response, compared with WT mice. Our data show for the first time that Fel d 1 is a novel ligand of the cysteine-rich domain of MR and that MR is likely to play a pivotal role in allergic sensitization to airborne allergens in vivo.


Assuntos
Asma/imunologia , Células Dendríticas/imunologia , Glicoproteínas/imunologia , Lectinas Tipo C/imunologia , Lectinas de Ligação a Manose/imunologia , Receptores de Superfície Celular/imunologia , Animais , Especificidade de Anticorpos/imunologia , Asma/genética , Asma/metabolismo , Gatos , Células Dendríticas/metabolismo , Inativação Gênica , Glicoproteínas/metabolismo , Glicoproteínas/farmacologia , Humanos , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/genética , Lectinas de Ligação a Manose/metabolismo , Camundongos , Camundongos Knockout , Ligação Proteica , Estrutura Terciária de Proteína , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo
15.
J Biol Chem ; 286(10): 7822-9, 2011 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-21205820

RESUMO

The mannose receptor (MR) is an endocytic type I membrane molecule with a broad ligand specificity that is involved in both hemostasis and pathogen recognition. Membrane-anchored MR is cleaved by a metalloproteinase into functional soluble MR (sMR) composed of the extracellular domains of intact MR. Although sMR production was initially considered a constitutive process, enhanced MR shedding has been observed in response to the fungal pathogen Pneumocystis carinii. In this work, we have investigated the mechanism mediating enhanced MR shedding in response to fungi. We show that other fungal species, including Candida albicans and Aspergillus fumigatus, together with zymosan, a preparation of the cell wall of Saccharomyces cerevisiae, mimic the effect of P. carinii on sMR production and that this effect takes place mainly through ß-glucan recognition. Additionally, we demonstrate that MR cleavage in response to C. albicans and bioactive particulate ß-glucan requires expression of dectin-1. Our data, obtained using specific inhibitors, are consistent with the canonical Syk-mediated pathway triggered by dectin-1 being mainly responsible for inducing MR shedding, with Raf-1 being partially involved. As in the case of steady-state conditions, MR shedding in response to C. albicans and ß-glucan particles requires metalloprotease activity. The induction of MR shedding by dectin-1 has clear implications for the role of MR in fungal recognition, as sMR was previously shown to retain the ability to bind fungal pathogens and can interact with numerous host molecules, including lysosomal hydrolases. Thus, MR cleavage could also impact on the magnitude of inflammation during fungal infection.


Assuntos
Fungos/metabolismo , Lectinas Tipo C/metabolismo , Macrófagos Peritoneais/metabolismo , Lectinas de Ligação a Manose/metabolismo , Proteínas de Membrana/metabolismo , Micoses/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Fungos/imunologia , Lectinas Tipo C/imunologia , Macrófagos Peritoneais/imunologia , Lectinas de Ligação a Manose/imunologia , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Micoses/imunologia , Proteínas do Tecido Nervoso/imunologia , Receptores de Superfície Celular/imunologia
16.
J Natl Med Assoc ; 97(6): 808-14, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16035580

RESUMO

PURPOSE: We conducted a cross-sectional study examining potentially modifiable factors associated with cognitive impairments (mild or severe) in older whites, African Americans and Hispanics attending an outpatient eye clinic. METHODS: In-clinic interviews and physical examinations assessed social, demographic and health information from 100 consecutive Hispanic, African-American and white adults aged > or = 55. Our primary outcome was presence of any cognitive impairment (mild or severe) using the St. Louis University Mental Status Examination (SLUMS) scale. RESULTS: Of the 100 subjects, 65 screened positive for cognitive impairments on the SLUMS cognitive instrument: 46 with mild cognitive impairment and 19 with severe impairment (possible dementia). African-American and Hispanic adults (nonwhites) were significantly more likely to have cognitive impairment compared to white adults (OR 2.80: 95% CI = 1.05-7.44), independent of age, years of education and systolic blood pressure. Subjects with diabetes also had increased odds of cognitive impairments (OR 3.28, 95% CI = 1.21-8.90) even after adjusting for relevant confounders. There was a nonsignificant trend between visual acuity impairment and cognitive impairment (p = 0.059). CONCLUSIONS: Sixty-five percent of adults aged > or = 55 attending the eye clinic screened positive for cognitive impairments, with higher rates among nonwhites and adults living with diabetes.


Assuntos
Transtornos Cognitivos/diagnóstico , Oftalmopatias/diagnóstico , Programas de Rastreamento/métodos , Afro-Americanos/estatística & dados numéricos , Idoso , Transtornos Cognitivos/etnologia , Estudos Transversais , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Oftalmopatias/etnologia , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Ambulatório Hospitalar , Prevalência
17.
South Med J ; 96(8): 796-8, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14515921

RESUMO

Cellulitis is usually caused by organisms such as beta-hemolytic streptococci and Staphylococcus aureus. Citrobacter are gram-negative bacilli that can cause opportunistic infections in immunocompromised hosts. They are rarely implicated in skin or soft tissue infections. The genus Citrobacter has been respeciated according to genetic relatedness. Citrobacter braakii refers to the genomospecies 6 of the Citrobacter freundii complex. There are no detailed studies of infections caused by the newly formed specific genetic species. We report a case of C. braakii infection in a renal transplant patient receiving immunosuppressive therapy. The patient's lower extremity cellulitis did not respond to conventional antibiotic therapy. Blood cultures grew C. braakii. Sensitivity studies and treatment with appropriate antibiotics resulted in prompt recovery. Immunosuppressive therapy in renal transplant recipients predisposes to infection by unusual pathogens, and this should be suspected when lack of a clinical response to conventional antibiotics is observed. We believe this is the first reported case of C. braakii cellulitis and bacteremia in a renal transplant recipient.


Assuntos
Bacteriemia/etiologia , Celulite (Flegmão)/etiologia , Citrobacter freundii/classificação , Infecções por Enterobacteriaceae/etiologia , Hospedeiro Imunocomprometido/imunologia , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Infecções Oportunistas/etiologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Aztreonam/uso terapêutico , Bacteriemia/tratamento farmacológico , Celulite (Flegmão)/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Resistência a Medicamentos , Quimioterapia Combinada/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Humanos , Transplante de Rim/imunologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ofloxacino/uso terapêutico , Infecções Oportunistas/tratamento farmacológico , Sorotipagem , Imunologia de Transplantes , Resultado do Tratamento
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