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BACKGROUND AND OBJECTIVE: The usefulness of the mast cell activation test (MAT) in diagnosing patients with uninterpretable basophil activation test (BAT) caused by nonresponding basophils has not yet been addressed. It should be further evaluated if the results of MAT are associated with the severity of the allergic reaction. METHODS: We recruited 39 Hymenoptera venom allergic (HVA) patients, 22 non-sensitized controls, and 37 BAT nonresponding HVA patients. Specific IgE levels for honey bee venom (HBV), yellow jacket venom (YJV) and total IgEs were quantified using the Immulite system. BAT and MAT with LAD2 cells in response to HBV and YJV were performed. RESULTS: We first optimized the susceptibility of LAD2 cells to IgE-mediated degranulation in HVA and showed that prestimulation with IL-33 and IL-6 significantly increased the LAD2 cells´ responsiveness to allergen stimulation (P<0.01). LAD2 MAT results correlated with BAT results, and patients with severe sting reactions (Mueller grades IV or III) had a median 2-fold higher LAD2 MAT than the patients with nonsevere sting reactions (Mueller grades II, I or LLR) (P<0.05). Further, LAD2 MAT provided conclusive results in 54.1% (20 of 37) of HVA patients with nonresponding basophils in the BAT. CONCLUSION: The LAD2 MAT represents a new diagnostic tool for HVA patients with nonresponding basophils. Further, LAD2 MAT can identify patients at risk of severe sting reactions and thus can help guide recommendations for venom immunotherapy and improve the management of patients with HVA.
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Antineoplásicos/uso terapéutico , Basófilos/patología , Neoplasias de la Mama/tratamiento farmacológico , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/terapia , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/terapia , Paclitaxel/uso terapéutico , Antineoplásicos/efectos adversos , Prueba de Desgranulación de los Basófilos , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/efectos adversos , Insuficiencia del TratamientoAsunto(s)
Humanos , Femenino , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/terapia , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/terapia , Insuficiencia del Tratamiento , Paclitaxel/efectos adversos , Antineoplásicos/efectos adversosRESUMEN
Prion diseases are caused by the misfolding of a host-encoded glycoprotein, PrPC, into a pathogenic conformer, PrPSc. Infectious prions can exist as different strains, composed of unique conformations of PrPSc that generate strain-specific biological traits, including distinctive patterns of PrPSc accumulation throughout the brain. Prion strains from different animal species display different cofactor and PrPC glycoform preferences to propagate efficiently in vitro, but it is unknown whether these molecular preferences are specified by the amino acid sequence of PrPC substrate or by the conformation of PrPSc seed. To distinguish between these two possibilities, we used bank vole PrPC to propagate both hamster or mouse prions (which have distinct cofactor and glycosylation preferences) with a single, common substrate. We performed reconstituted sPMCA reactions using either (1) phospholipid or RNA cofactor molecules, or (2) di- or un-glycosylated bank vole PrPC substrate. We found that prion strains from either species are capable of propagating efficiently using bank vole PrPC substrates when reactions contained the same PrPC glycoform or cofactor molecule preferred by the PrPSc seed in its host species. Thus, we conclude that it is the conformation of the input PrPSc seed, not the amino acid sequence of the PrPC substrate, that primarily determines species-specific cofactor and glycosylation preferences. These results support the hypothesis that strain-specific patterns of prion neurotropism are generated by selection of differentially distributed cofactors molecules and/or PrPC glycoforms during prion replication.
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Proteínas PrPC/metabolismo , Enfermedades por Prión/metabolismo , Priones/metabolismo , Secuencia de Aminoácidos , Animales , Arvicolinae , Encéfalo/patología , Enfermedades Transmisibles/metabolismo , Cricetinae , Glicosilación , Mesocricetus , Ratones , Ratones Endogámicos C57BL , Conformación Molecular , Proteínas PrPSc/metabolismo , Especificidad de la EspecieRESUMEN
BACKGROUND: Tranilast [N-(3,4-dimethoxycinnamoyl) anthranilic acid] has never been investigated for the prevention and treatment of acne scars. AIM: To evaluate the efficacy and safety of tranilast 8% gel in improving the final appearance of patients with acne scarring concomitantly treated by isotretinoin. METHODS: This was a prospective, double-blind, split-face study, which enrolled 40 otherwise healthy participants (aged 18-49 years) with facial acne scars. For each patient, one half of the face were treated with tranilast 8% liposomal gel and the other half with a water-based placebo. Using the Global Aesthetic Improvement Scale (GAIS), acne scars were evaluated by two dermatologists and by the patients, and the patients also rated their satisfaction with the treatment and reported adverse effects. RESULTS: In total, 32 participants completed the trial. The mean GAIS scores at 5 months post-treatment were significantly lower (better outcome) for the tranilast-treated side than the placebo-treated areas in patients concomitantly treated with isotretinoin (P < 0.001). All the isotretinoin-treated patients reported greater satisfaction and better general improvement in the skin's appearance and texture, and also greater improvement of pigment and redness on the tranilast 8% gel-treated side compared with the control side. CONCLUSION: Combined topical application of tranilast 8% gel twice daily with oral isotretinoin treatment in the active phase of acne vulgaris may result in fewer scars, finer skin texture and enhanced appearance.
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Acné Vulgar/complicaciones , Cicatriz/tratamiento farmacológico , Fármacos Dermatológicos/administración & dosificación , Isotretinoína/uso terapéutico , ortoaminobenzoatos/administración & dosificación , Administración Cutánea , Administración Oral , Adolescente , Adulto , Cicatriz/etiología , Método Doble Ciego , Quimioterapia Combinada , Femenino , Geles , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Severely debilitating plantar keratoderma pain is the most distressing clinical feature of pachyonychia congenita (PC). Several earlier publications have reported therapeutic success with plantar injections of botulinum toxin (Btx). OBJECTIVES: To describe our 4-year experience during which we administered a total of 30 plantar Btx injections to five patients with PC following an optimized protocol. METHODS: Five patients with PC (age 21-54 years) who were treated at our medical centre from April 2015 to June 2018 were included in the study. After an ultrasound-guided nerve block performed by an anaesthesiologist, the patients received plantar intradermal injections of Btx A. To ascertain the effect of the treatment, we used a dedicated quality-of-life questionnaire for patients with PC (PCQoL) and asked the patients to evaluate the intensity of eight parameters pertaining to their symptoms at baseline and before every treatment session. At study closure, patients were asked to evaluate the maximal improvement in the same eight parameters throughout the study period. RESULTS: All patients demonstrated a decrease in PCQoL scores during the follow-up period. All patients showed a significant improvement in PCQoL after the first treatment session and at the last evaluation (P = 0·043). The scores with the best improvement concerned morning feet burning and long-distance walking (> 500 m). The scores were significantly lower if the intervals between Btx injections were <100 days. CONCLUSIONS: Btx treatment of PC-associated keratoderma following an optimized protocol leads to a major change in patients' quality of life. What's already known about this topic? Plantar pain is considered by patients to be the most severe and debilitating manifestation of pachyonychia congenita (PC). Over the past few years, a number of reports have shown that plantar injections of botulinum toxin (Btx) reduce or even eliminate pain, blistering and callosities in patients with PC. However, the injection technique, doses of Btx and methods of anaesthesia varied between reports and patients. What does this study add? Here we report our 4-year experience in providing 30 treatments to five patients following an optimized protocol. Btx was found to provide a quantifiable improvement in all patients treated. What is the translational message? Btx treatment of PC-associated keratoderma using a structured approach, which includes the use of a sufficient dose of Btx (200-400 U of onabotulinumtoxinA or 500-1000 U of abobotulinumtoxinA), and regular intervals between treatment sessions (of < 100 days), leads to a major change in patients' quality of life.
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Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Paquioniquia Congénita , Adulto , Toxinas Botulínicas Tipo A/uso terapéutico , Protocolos Clínicos , Humanos , Inyecciones Intradérmicas , Persona de Mediana Edad , Paquioniquia Congénita/complicaciones , Paquioniquia Congénita/tratamiento farmacológico , Calidad de Vida , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Treatment options for atrophic acne scars include the use of various energy-based devices (EBDs) and dermal fillers. AIM: To evaluate the level of improvement and safety of four treatments for atrophic acne scars used in our centre. METHODS: We reviewed the medical records of all patients with acne scars treated between 2013 and 2016 with one of four treatments: ablative fractional CO2 laser (FACL), a radiofrequency (RF) bipolar device, a 1540 nm nonablative fractional laser (NAFL) and injection of diluted calcium hydroxylapatite (CaHA). The EBDs were used either as monotherapy or in combination with diluted CaHA. The aesthetic improvement achieved following the various treatments was evaluated by the patients and by two independent dermatologists who were not involved in the treatments. The patients also rated their satisfaction with the treatment, recorded the number of days of downtime (including time to full recovery and time for resolution of redness) and reported any adverse effects (AEs). RESULTS: In total, 352 patients (mean ± SD age 28.7 ± 8.7 years; 65.6% women, 34.4% men) were treated for acne scars. The integrated mean Global Assessment Scale by both dermatologists and patients were highest for the combined CaHA-FACL treatment at separate sessions (injection in one session; laser treatment in another) (P < 0.001). However, patients treated with FACL reported more AEs and longer downtime and duration of erythema. CONCLUSION: The combination of a diluted CaHA-based filler injection followed by FACL in separate treatment sessions yielded better aesthetic improvement compared with the other tested treatments.
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Acné Vulgar/complicaciones , Cicatriz/terapia , Rellenos Dérmicos/uso terapéutico , Durapatita/uso terapéutico , Terapia por Láser/métodos , Terapia por Radiofrecuencia/métodos , Adulto , Cicatriz/etiología , Terapia Combinada , Cara , Femenino , Humanos , Láseres de Gas/uso terapéutico , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: T cells play a major role in delayed-type hypersensitivity reactions. Their reactivity can be assessed by measuring the upregulation of the activation marker CD69, followed by assessment of proliferation and cytokine production. The aim of our study was to develop a novel, whole blood-based, quantitative, absolute count activation index (AI) for analysis of CD69 upregulation in various subsets of T cells in nickel-hypersensitive patients and compare it with previously reported approaches. METHODS: The study population comprised 10 patients with nickel allergy and 9 healthy controls. CD69 expression of CD3+, CD3+CD4+, and CD3+CD8+ T cells in heparinized blood was determined with flow cytometry after incubation with nickel sulfate for 48 hours. The absolute count of CD69+ cells was determined using microbeads. Production of the cytokines IL-2, IL-5, IL-13, and IFN-γ was determined after stimulation of peripheral blood mononuclear cells with nickel sulfate for 48 hours. RESULTS: We showed absolute AI to be the most sensitive approach. The index was calculated as the ratio of the absolute count of nickel-stimulated CD69-positive T cells to the absolute count of CD69-positive T cells in nonstimulated blood. This novel quantitative approach was more discriminative than previously reported approaches in which the T-cell CD69 percentage AI and cytokine production are measured. CONCLUSIONS: Our results demonstrated that measuring the absolute CD69 AI is a novel and accurate approach for quantification of antigen-specific T cells in the blood of patients with hypersensitivity reactions to nickel. This approach may be useful for better in vitro assessment of patients with delayed-type hypersensitivity reactions.
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Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Hipersensibilidad Tardía/diagnóstico , Hipersensibilidad Tardía/etiología , Lectinas Tipo C/metabolismo , Recuento de Linfocitos , Níquel/efectos adversos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Alérgenos/inmunología , Biomarcadores , Estudios de Casos y Controles , Citocinas/metabolismo , Humanos , Inmunofenotipificación , Activación de LinfocitosRESUMEN
BACKGROUND: Autophagy is a catabolic process involving the engulfment of cytoplasmic content within autophagosomes followed by their delivery to lysosomes. This process is a survival mechanism, enabling cells to cope with nutrient deprivation by degradation and recycling of macromolecules. Yet during continued stress such as prolonged starvation, a switch from autophagy to apoptosis is often detected. OBJECTIVE: In this work, we characterized the temporal dynamics of the transition from autophagy towards apoptosis with the aim of elucidating the molecular mechanism regulating the switch from survival autophagy to apoptotic cell death. RESULTS AND CONCLUSIONS: We defined an inverse relationship between apoptosis and autophagy spanning a period of 72 h, manifested by the sequential reduction in LC3 lipidation and the activation of caspase-3. The transition to apoptosis correlated with a selective decline in the mRNA and protein levels of two anti-apoptotic IAP family proteins, survivin and cIAP2 and a selective increase in the BH3-only protein, BimEL. This 'molecular signature' was common to several cell lines undergoing the switch from autophagy to apoptosis during prolonged starvation. Mechanistically, the increased BimEL protein levels resulted from its reduced binding to its specific E3 ligase, ßTrCP, leading to protein stabilization. Consistent with this, BimEL showed decreased phosphorylation at critical sites previously reported to be essential for binding to the E3 ligase. The decrease in the anti-apoptotic IAPs and the increase in the pro-apoptotic BimEL may thus constitute a molecular switch from autophagy to apoptosis during prolonged starvation.
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Apoptosis/fisiología , Autofagia/fisiología , Proteína 11 Similar a Bcl2/metabolismo , Proteínas Inhibidoras de la Apoptosis/metabolismo , Inanición/fisiopatología , Ubiquitina-Proteína Ligasas/metabolismo , Células A549 , Proteínas Relacionadas con la Autofagia/metabolismo , Proteína 3 que Contiene Repeticiones IAP de Baculovirus , Células Cultivadas , Humanos , Survivin , Proteínas con Repetición de beta-Transducina/metabolismoRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0154412.].
RESUMEN
The glaucomas are a group of diseases characterized by optic nerve damage that together represent a leading cause of blindness in the human population and in domestic animals. Here we report a mutation in LTBP2 that causes primary congenital glaucoma (PCG) in domestic cats. We identified a spontaneous form of PCG in cats and established a breeding colony segregating for PCG consistent with fully penetrant, autosomal recessive inheritance of the trait. Elevated intraocular pressure, globe enlargement and elongated ciliary processes were consistently observed in all affected cats by 8 weeks of age. Varying degrees of optic nerve damage resulted by 6 months of age. Although subtle lens zonular instability was a common feature in this cohort, pronounced ectopia lentis was identified in less than 10% of cats examined. Thus, glaucoma in this pedigree is attributed to histologically confirmed arrest in the early post-natal development of the aqueous humor outflow pathways in the anterior segment of the eyes of affected animals. Using a candidate gene approach, significant linkage was established on cat chromosome B3 (LOD 18.38, θ = 0.00) using tightly linked short tandem repeat (STR) loci to the candidate gene, LTBP2. A 4 base-pair insertion was identified in exon 8 of LTBP2 in affected individuals that generates a frame shift that completely alters the downstream open reading frame and eliminates functional domains. Thus, we describe the first spontaneous and highly penetrant non-rodent model of PCG identifying a valuable animal model for primary glaucoma that closely resembles the human disease, providing valuable insights into mechanisms underlying the disease and a valuable animal model for testing therapies.
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Enfermedades de los Gatos/genética , Glaucoma/veterinaria , Proteínas de Unión a TGF-beta Latente/genética , Animales , Humor Acuoso/fisiología , Enfermedades de los Gatos/congénito , Gatos , Femenino , Ligamiento Genético , Glaucoma/congénito , Glaucoma/genética , Presión Intraocular/genética , Proteínas de Unión a TGF-beta Latente/fisiología , Masculino , Mutación/genética , Linaje , Fenotipo , Células Ganglionares de la Retina/patologíaRESUMEN
Infectious prions contain a self-propagating, misfolded conformer of the prion protein termed PrPSc. A critical prediction of the protein-only hypothesis is that autocatalytic PrPSc molecules should be infectious. However, some autocatalytic recombinant PrPSc molecules have low or undetectable levels of specific infectivity in bioassays, and the essential determinants of recombinant prion infectivity remain obscure. To identify structural and functional features specifically associated with infectivity, we compared the properties of two autocatalytic recombinant PrP conformers derived from the same original template, which differ by >105-fold in specific infectivity for wild-type mice. Structurally, hydrogen/deuterium exchange mass spectrometry (DXMS) studies revealed that solvent accessibility profiles of infectious and non-infectious autocatalytic recombinant PrP conformers are remarkably similar throughout their protease-resistant cores, except for two domains encompassing residues 91-115 and 144-163. Raman spectroscopy and immunoprecipitation studies confirm that these domains adopt distinct conformations within infectious versus non-infectious autocatalytic recombinant PrP conformers. Functionally, in vitro prion propagation experiments show that the non-infectious conformer is unable to seed mouse PrPC substrates containing a glycosylphosphatidylinositol (GPI) anchor, including native PrPC. Taken together, these results indicate that having a conformation that can be specifically adopted by post-translationally modified PrPC molecules is an essential determinant of biological infectivity for recombinant prions, and suggest that this ability is associated with discrete features of PrPSc structure.
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Enfermedades Transmisibles/inmunología , Enfermedades Transmisibles/metabolismo , Proteínas PrPC/metabolismo , Proteínas PrPSc/metabolismo , Priones/metabolismo , Animales , Biocatálisis , Modelos Animales de Enfermedad , Ratones , Procesamiento Proteico-Postraduccional/inmunologíaRESUMEN
BACKGROUND: The FYB gene encodes adhesion and degranulation-promoting adaptor protein (ADAP), a hematopoietic-specific protein involved in platelet activation, cell motility and proliferation, and integrin-mediated cell adhesion. No ADAP-related diseases have been described in humans, but ADAP-deficient mice have mild thrombocytopenia and increased rebleeding from tail wounds. PATIENTS AND METHODS: We studied a previously reported family of five children from two consanguineous sibships of Arab Christian descent affected with a novel autosomal recessive bleeding disorder with small-platelet thrombocytopenia. Homozygosity mapping and exome sequencing were used to identify the genetic lesion causing the disease phenotype on chromosome 5. Bone-marrow morphology and platelet function were analyzed. Platelets were characterized by scanning electron microscopy. RESULTS: We identified a homozygous deleterious nonsense mutation, c.393G>A, in FYB. A reduced percentage of mature megakaryocytes was found in the bone marrow. Patients' platelets showed increased basal expression of P-selectin and PAC-1, and reduced increments of activation markers after stimulation with ADP, as detected by flow cytometry; they also showed reduced pseudopodium formation and the presence of trapped platelets between the fibrin fibers after thrombin addition, as observed on scanning electron microscopy. CONCLUSIONS: This is the first report of a disease caused by an FYB defect in humans, manifested by remarkable small-platelet thrombocytopenia and a significant bleeding tendency. The described phenotype shows ADAP to be important for normal platelet production, morphologic changes, and function. It is suggested that mutation analysis of this gene be included in the diagnosis of inherited thrombocytopenia.
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Proteínas Adaptadoras Transductoras de Señales/genética , Plaquetas/ultraestructura , Codón sin Sentido , Hemorragia/genética , Hemostasis/genética , Trombocitopenia/genética , Árabes/genética , Plaquetas/metabolismo , Tamaño de la Célula , Análisis Mutacional de ADN , Fosfatasa 2 de Especificidad Dual/sangre , Exoma , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Hemorragia/sangre , Hemorragia/diagnóstico , Hemorragia/etnología , Heterocigoto , Homocigoto , Humanos , Israel/epidemiología , Microscopía Electrónica de Rastreo , Selectina-P/sangre , Linaje , Fenotipo , Pruebas de Función Plaquetaria , Valor Predictivo de las Pruebas , Factores de Riesgo , Trombocitopenia/sangre , Trombocitopenia/diagnóstico , Trombocitopenia/etnologíaRESUMEN
PURPOSE: Patients with hemoglobinopathies who undergo splenectomy are at risk for invasive infections. The aim of this investigation was to present the clinical spectrum of infections in splenectomized patients. METHODS: The study cohort comprised 54 splenectomized patients with beta-thalassemia (ß-thalassemic) and sickle cell disease. The incidence of serious invasive bacterial infections was recorded. All patients received pneumococcal vaccine and all received oral prophylactic penicillin. RESULTS: A total of 22 episodes of serious bacterial infections were identified in 19 patients among the study cohort of 54 splenectomized patients (35%). The clinical spectrum included sepsis (10 patients), bacteremia (8), liver abscess (1), forearm abscess (1), and urinary tract infection (2). The most frequent pathogens were Escherichia coli (8 cases), Steptococcus pneumoniae (5), and Campylobacter (2). 22 patients with ß thalassemia died during the study period: 6 due to bacterial infection and 18 due to cardiomyopathy. The time elapsed between splenectomy and S. pneumoniae infection was significantly shorter than that between splenectomy and infections caused by other pathogens (18 ± 14 vs. 115 ± 93 months, respectively; p = 0.035). CONCLUSIONS: Splenectomized patients with ß thalassemia and sickle cell disease are predisposed to severe infections, with the majority of these infections being caused by Gram-negative microorganisms. The attending physician(s) should take these findings into consideration when deciding upon an empiric antibiotic treatment for splenectomized patients who present with fever or sepsis.
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Anemia de Células Falciformes/complicaciones , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Esplenectomía/efectos adversos , Talasemia beta/complicaciones , Adolescente , Adulto , Antibacterianos/uso terapéutico , Bacterias/clasificación , Bacterias/aislamiento & purificación , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/mortalidad , Niño , Preescolar , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Incidencia , Israel/epidemiología , Penicilinas/uso terapéutico , Vacunas Neumococicas/uso terapéutico , Factores de RiesgoRESUMEN
BACKGROUND: Studies of Glanzmann thrombasthenia (GT)-causing mutations has generated invaluable information on the formation and function of integrin αIIbß(3). OBJECTIVE: To characterize the mutation in four siblings of an Israeli Arab family affected by GT, and to analyze the relationships between the mutant protein structure and its function using artificial mutations. METHODS AND RESULTS: Sequencing disclosed a new A97G transversion in the αIIb gene predicting Asn2Asp substitution at blade 1 of the ß-propeller. Alignment with other integrin α subunits revealed that Asn2 is highly conserved. No surface expression of αIIbß(3) was found in patients' platelets and baby hamster kidney (BHK) cells transfected with mutated αIIb and WT ß(3). Although the αIIbß(3) was formed, the mutation impaired its intracellular trafficking. Molecular dynamics simulations and modeling of the αIIbß(3) crystal indicated that the Asn2Asp mutation disrupts a hydrogen bond between Asn2 and Leu366 of a calcium binding domain in blade 6, thereby impairing calcium binding that is essential for intracellular trafficking of αIIbß(3). Substitution of Asn2 to uncharged Ala or Gln partially decreased αIIbß(3) surface expression, while substitution by negatively or positively charged residues completely abolished surface expression. Unlike αIIbß(3), αVß(3) harboring the Asn2Asp mutation was surface expressed by transfected BHK cells, which is consistent with the known lower sensitivity of αVß(3) to calcium chelation compared with αIIbß(3). CONCLUSION: The new GT causing mutation highlights the importance of calcium binding domains in the ß-propeller for intracellular trafficking of αIIbß(3). The mechanism by which the mutation exerts its deleterious effect was elucidated by molecular dynamics.
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Plaquetas/metabolismo , Calcio/metabolismo , Integrina alfa2/genética , Mutación , Trombastenia/genética , Adolescente , Secuencia de Aminoácidos , Animales , Árabes/genética , Asparagina , Ácido Aspártico , Sitios de Unión , Calcio/sangre , Línea Celular , Niño , Preescolar , Cricetinae , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Glutamina , Hemostasis/genética , Herencia , Humanos , Enlace de Hidrógeno , Integrina alfa2/sangre , Integrina alfa2/química , Integrina beta3/sangre , Israel , Leucina , Masculino , Modelos Moleculares , Datos de Secuencia Molecular , Linaje , Fenotipo , Conformación Proteica , Estructura Terciaria de Proteína , Transporte de Proteínas , Trombastenia/sangre , Trombastenia/etnología , TransfecciónRESUMEN
Staphylococcus aureus is widely appreciated as an opportunistic pathogen, primarily in hospital-related infections. However, recent reports indicate that S. aureus infections can now occur in other wise healthy individuals in the community setting. The success of this organism can be attributed to the large array of regulatory proteins, including the SarA protein family, used to respond to changing microenvironments. Sequence alignment and structural data reveal that the SarA protein family can be divided into three subfamilies: (1) single domain proteins; (2) double domain proteins; (3) MarR homologs. Structural studies have also demonstrated that SarA, SarR, SarS, MgrA and thus possibly all members of this protein family are winged helix proteins with minor variations. Mutagenesis studies of SarA disclose that the winged helix motifs are important for DNA binding and function. Recent progress concerning the functions and plausible mechanisms of regulation of SarA and its homologs are discussed.
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Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/patogenicidad , Secuencia de Aminoácidos , Humanos , Datos de Secuencia Molecular , Estructura Secundaria de Proteína , Alineación de Secuencia , Staphylococcus aureus/metabolismo , VirulenciaAsunto(s)
Western Blotting/métodos , Glicosilfosfatidilinositoles/metabolismo , Proteínas/análisis , Fosfolipasas de Tipo C/metabolismo , Animales , Western Blotting/instrumentación , Cricetinae , Proteínas PrPC/análisis , Proteínas PrPC/genética , Proteínas PrPC/metabolismo , Proteínas/genética , Proteínas/metabolismo , Proteínas Recombinantes/análisis , Proteínas Recombinantes/metabolismo , Reproducibilidad de los ResultadosRESUMEN
The specificity of management of quality work of nurses during providing medical care to patients in an intensive care unit is considered in the article. It is noticed, that the quality of getting medical care to critically ill patients depends on psychological state of the staff. The key factors providing the qualitative work of the medical personnel with critically ill patients are follows as: preliminary occupational selection, team interaction, trainings, moral and financial work motivation, effective system of control of medical care and consideration of mistakes. The instruments for quality control and reasons raising risks of nurse mistakes are presented in the article.
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Enfermedad Crítica/enfermería , Atención a la Salud , Personal de Enfermería en Hospital/normas , Gestión de la Calidad Total/métodos , Atención a la Salud/organización & administración , Atención a la Salud/normas , Humanos , UcraniaRESUMEN
OBJECTIVE: To examine the possible usefulness of simple and quick criteria for identifying febrile neonates with low risk for serious bacterial infection (SBI). DESIGN: All febrile neonates who were admitted between August 1998 and August 2003 to the Pediatric Emergency Department, HaEmek Medical Center, Afula, Israel, and to the Poriya Hospital, Tiberias, Israel, were included in the study. The recommended evaluation of each neonate included details of medical history and a complete physical examination, including blood culture, erythrocyte sedimentation rate (ESR), white cell count (WBC), and analysis and culture of urine and cerebrospinal fluid. Other tests were carried out as necessary. Patients who met all the following criteria were considered to have low risk for SBI: (1) unremarkable medical history; (2) good appearance; (3) no focal physical signs of infection; (4) ESR <30 mm at the end of the first hour; (5) WBC 5000-15 000/mm(3); (6) a normal urine analysis by the dipstick method. RESULTS: Complete data were available for 386 neonates. SBI was documented in 108 (28%) neonates, of whom 14% had a urinary tract infection, 9.3% had acute otitis media, 2.3% had pneumonia, 1.3% had cellulitis, 0.5% had bacterial meningitis and 0.5% had bacterial gastroenteritis. The overall incidence of SBI was 1 in 166 (0.6%) neonates who fulfilled the criteria compared with 107 in 220 (48.6%) in the neonates who did not fulfil the criteria (p<0.001). The negative predictive value for SBI of the combination of the low-risk criteria was 99.4% (95% confidence interval 99.35% to 99.45%). CONCLUSIONS: Fulfillment of the criteria for low risk might be a reliable and useful tool for excluding SBI in febrile neonates.