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1.
Nat Immunol ; 11(9): 836-45, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20676093

RESUMEN

BAFF and APRIL are innate immune mediators that trigger immunoglobulin G (IgG) and IgA class-switch recombination (CSR) in B cells by engaging the receptor TACI. The mechanism that underlies CSR signaling by TACI remains unknown. Here we found that the cytoplasmic domain of TACI encompasses a conserved motif that bound MyD88, an adaptor that activates transcription factor NF-kappaB signaling pathways via a Toll-interleukin 1 (IL-1) receptor (TIR) domain. TACI lacks a TIR domain, yet triggered CSR via the DNA-editing enzyme AID by activating NF-kappaB through a Toll-like receptor (TLR)-like MyD88-IRAK1-IRAK4-TRAF6-TAK1 pathway. TACI-induced CSR was impaired in mice and humans lacking MyD88 or the kinase IRAK4, which indicates that MyD88 controls a B cell-intrinsic, TIR-independent, TACI-dependent pathway for immunoglobulin diversification.


Asunto(s)
Linfocitos B/inmunología , Cambio de Clase de Inmunoglobulina/inmunología , Factor 88 de Diferenciación Mieloide/inmunología , Proteína Activadora Transmembrana y Interactiva del CAML/inmunología , Animales , Células Cultivadas , Humanos , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Transducción de Señal
2.
J Clin Immunol ; 41(3): 639-657, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33417088

RESUMEN

PURPOSE: Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown. METHODS: We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives. RESULTS: We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mycobacterial disease and were also heterozygous, resulting in 18 patients in total. Mycobacterial infection was the first clinical manifestation in 11 patients, at a mean age of 22.5 years (range: 12 to 42 years). Most patients also suffered from other infections, monocytopenia, or myelodysplasia. Strikingly, the clinical penetrance was incomplete (32.9% by age 40 years), as 16 heterozygous relatives aged between 6 and 78 years, including 4 older than 60 years, were completely asymptomatic. CONCLUSION: Clinical penetrance for mycobacterial disease was found to be similar to other GATA2 deficiency-related manifestations. These observations suggest that other mechanisms contribute to the phenotypic expression of GATA2 deficiency. A diagnosis of autosomal dominant GATA2 deficiency should be considered in patients with mycobacterial infections and/or other GATA2 deficiency-related phenotypes at any age in life. Moreover, all direct relatives should be genotyped at the GATA2 locus.


Asunto(s)
Deficiencia GATA2/diagnóstico , Deficiencia GATA2/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haploinsuficiencia , Penetrancia , Fenotipo , Adolescente , Adulto , Alelos , Línea Celular , Niño , Análisis Mutacional de ADN , Bases de Datos Genéticas , Femenino , Deficiencia GATA2/epidemiología , Genes Dominantes , Estudios de Asociación Genética/métodos , Genotipo , Mutación de Línea Germinal , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/etiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/etiología , Evaluación de Resultado en la Atención de Salud , Linaje , Secuenciación del Exoma , Adulto Joven
3.
Dermatol Online J ; 23(3)2017 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-28329526

RESUMEN

Chronic granulomatous disease (CGD) is a primaryimmunodeficiency disorder that affects the phagocyticcells of the innate immune system. It is characterizedby recurrent or persistent infections with granulomaformation. Lupus-like lesions have been reported incarriers of CGD and less frequently, in patients withCGD. Immunological study in these patients areusually negative. We describe the case of an 8-yearoldboy with CGD who developed chronic and acutecutaneous lupus erythematous with angular cheilitis,oral ulcers, Raynaud phenomenon, and positiveserologies for antinuclear, anticentromere, and anti-Saccharomyces cerevisiae antibodies.


Asunto(s)
Dermatosis Facial/diagnóstico , Dermatosis del Pie/diagnóstico , Enfermedad Granulomatosa Crónica/inmunología , Lupus Eritematoso Cutáneo/diagnóstico , Anticuerpos Antinucleares/inmunología , Anticuerpos Antifúngicos/inmunología , Queilitis/complicaciones , Queilitis/diagnóstico , Queilitis/inmunología , Niño , Dermatosis Facial/complicaciones , Dermatosis Facial/inmunología , Dermatosis Facial/patología , Dermatosis del Pie/complicaciones , Dermatosis del Pie/inmunología , Dermatosis del Pie/patología , Enfermedad Granulomatosa Crónica/complicaciones , Humanos , Lupus Eritematoso Cutáneo/complicaciones , Lupus Eritematoso Cutáneo/inmunología , Lupus Eritematoso Cutáneo/patología , Masculino , Úlceras Bucales/complicaciones , Úlceras Bucales/diagnóstico , Úlceras Bucales/inmunología , Enfermedad de Raynaud/complicaciones , Enfermedad de Raynaud/diagnóstico , Enfermedad de Raynaud/inmunología , Factores de Riesgo , Saccharomyces cerevisiae/inmunología
4.
Blood ; 120(25): 4992-5001, 2012 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-23002119

RESUMEN

We studied the distribution of peripheral B-cell subsets in patients deficient for key factors of the TLR-signaling pathways (MyD88, TIRAP/MAL, IL-1 receptor-associated kinase 4 [IRAK-4], TLR3, UNC-93B, TRIF). All TLRs, except TLR3, which signals through the TRIF adaptor, require MyD88 and IRAK-4 to mediate their function. TLR4 and the TLR2 heterodimers (with TLR1, TLR6, and possibly TLR10) require in addition the adaptor TIRAP, whereas UNC-93B is needed for the proper localization of intracellular TLR3, TLR7, TLR8, and TLR9. We found that IgM(+)IgD(+)CD27(+) but not switched B cells were strongly reduced in MyD88-, IRAK-4-, and TIRAP-deficient patients. This defect did not appear to be compensated with age. However, somatic hypermutation of Ig genes and heavy-chain CDR3 size distribution of IgM(+)IgD(+)CD27(+) B cells were not affected in these patients. In contrast, the numbers of IgM(+)IgD(+)CD27(+) B cells were normal in the absence of TLR3, TRIF, and UNC-93B, suggesting that UNC-93B-dependent TLRs, and notably TLR9, are dispensable for the presence of this subset in peripheral blood. Interestingly, TLR10 was found to be expressed at greater levels in IgM(+)IgD(+)CD27(+) compared with switched B cells in healthy patients. Hence, we propose a role for TIRAP-dependent TLRs, possibly TLR10 in particular, in the development and/or maintenance of IgM(+)IgD(+)CD27(+) B cells in humans.


Asunto(s)
Linfocitos B/inmunología , Inmunoglobulina D/inmunología , Inmunoglobulina M/inmunología , Quinasas Asociadas a Receptores de Interleucina-1/genética , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana/genética , Factor 88 de Diferenciación Mieloide/genética , Receptores de Interleucina-1/genética , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Adolescente , Adulto , Linfocitos B/patología , Niño , Preescolar , Citocinas/inmunología , Humanos , Inmunoglobulina D/análisis , Inmunoglobulina M/análisis , Mutación , Receptor Toll-Like 10/genética , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/análisis , Adulto Joven
5.
J Bodyw Mov Ther ; 38: 437-448, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38763590

RESUMEN

BACKGROUND: Easy access to the Internet enables the creation of many online applications. In this sense, questionnaires were developed to evaluate the usability of health area online applications: the National Usability-Focused Health Information System Scale (NuHISS), the Enlight, and the User Version of the Mobile Application Rating Scale (uMARS). Those scales do not have a Portuguese (Brazil) version which is adequate to Brazil's culture. As a consequence, they can not be properly used in Brazil. OBJECTIVE: To translate and cross-cultural adapt the NuHISS, Enlight, and uMARS to Portuguese (Brazil). METHODS: A methodological study involving the translation and cross-cultural adaptation of the questionnaires NuHISS, Enlight, and uMARS was conducted following international guidelines recommendations. The questionnaires pass trough an initial translation, translation synthesis, back translation, expert committee, and a pre-final version test. RESULTS: Thirdy-two health professionals analyzed NuHiss, Enlight, and uMARS translated and cross-cultural adapted Portuguese (Brazil) version. There was conceptual equivalence between the translated and original versions, and no significant adaptations were needed during the translation process. 93.8% of professionals assume that the language is cohesive and 96.9% of them consider that the content is cohesive. CONCLUSION: The NuHISS, Enlight, and uMARS were successfully translated and cross-culturally adapted to Portuguese (Brazil) and can be properly applied in Brazil. Brazilian health professionals should use the questionnaires NuHISS, Enlight, and uMARS to evaluate health area applications usability.


Asunto(s)
Comparación Transcultural , Traducciones , Humanos , Brasil , Encuestas y Cuestionarios , Lenguaje , Femenino , Sistemas de Información en Salud/normas , Masculino , Internet , Adulto
6.
J Exp Med ; 221(5)2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38557723

RESUMEN

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαß+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αß T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.


Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T Colaboradores-Inductores , Humanos , Linfocitos T CD8-positivos , Activación de Linfocitos , Antígenos HLA , Isoformas de Proteínas/metabolismo
7.
J Bodyw Mov Ther ; 35: 64-68, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37330804

RESUMEN

INTRODUCTION: Some previous studies investigated predictors of balance in individuals with Parkinson's Disease (PD). However, outcomes commonly evaluated in the rehabilitation of individuals with PD that could predict balance deficits have not yet been investigated. OBJECTIVE: To determine whether the variables muscle strength, physical activity and depression are predictors of balance in individuals with PD. MATERIAL AND METHODS: This is a cross-sectional study in which the investigated variables included: trunk and knee extensors' muscle strength (modified sphygmomanometer test - MST), physical activity level (Adjusted Human Activity Profile score) and depression (Patient Health Questionnaire-9 - PHQ-9). The outcome variable was balance, as assessed by the Mini-BESTest. Multiple regression analysis was used to determine which predictor variables explain the outcome variable. RESULTS: A total of 50 individuals with PD, mean age 67 ± 8.8 years, 68% male, 40% HY 2.5 were included. The mean value of the dominant limb extensor muscle strength was 139 ± 45 mmHg, and the mean trunk extensor muscle strength value was 81.9 ± 19 mmHg. More than half of the sample (52%, n = 26) was classified as moderately active. Most of the sample (78%) had mild depression. The average Mini-BESTest score was 21 ± 5.4. The physical activity level explained 29% of the balance variance. When depression was included in the model, the explained variance increased to 35%. The other independent variables were not included in the model. CONCLUSION: The findings of the present study showed that the physical activity level and depression were able to explain 35% of the balance variation.


Asunto(s)
Enfermedad de Parkinson , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Estudios Transversales , Rodilla , Extremidad Inferior , Ejercicio Físico , Equilibrio Postural/fisiología
8.
Int Urol Nephrol ; 55(11): 2867-2875, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37186212

RESUMEN

Diethylene glycol (DEG) is nephrotoxic, potentially resulting in high morbidity and mortality. Its main nephrotoxic by-product is diglycolic acid (DGA). This narrative overview summarizes selected literature with a focus on clinical findings, pathophysiology, diagnosis including morphological features of renal biopsies, and management. The kidney injury in DEG poisoning is secondary to proximal tubular necrosis caused by DGA. Marked vacuolization and edema of epithelial cells obstruct the lumen, reducing urine flow and, consequently, resulting in anuria and uremia. The clinical alterations due to DEG poisoning are dose-dependent. Patients may present with gastrointestinal symptoms and anion gap metabolic acidosis, followed by renal failure, and, later, encephalopathy and neuropathy. Although this three-phase pattern has been described, signs and symptoms may be overlapping. Data about DEG intoxication is scarce. Sometimes the diagnosis is challenging. The management includes supportive care, gastric decontamination, correction of acid-base disorders, and hemodialysis. The understanding of the metabolic processes related to DEG poisoning may contribute to its management, preventing death, serious sequels, or irreversible lesions.

9.
Clin Chim Acta ; 528: 56-64, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35092724

RESUMEN

BACKGROUND: Automated, technically simple analytical methods offering objective results are highly valued in clinical laboratories. Kappa free light chains (KFLC) in cerebrospinal fluid (CSF) are promising multiple sclerosis (MS) biomarkers, particularly kappa (K) index. METHODS: KFLC were determined in CSF and serum samples of patients diagnosed with MS, clinically/radiologically isolated syndrome (N, 39), and controls (N, 152; inflammatory and non-inflammatory neurological disorders). Diagnostic performance of several KFLC parameters, previously determined oligoclonal band (OCB) testing, and IgG index, was assessed. A K index decision threshold for sample screening was identified and reduction in performed OCB analyses estimated accordingly. RESULTS: Higher KFLC parameters were detected in the MS group and K index performed best among them (AUC 0.92). At a 7.25 cut-off it showed better sensitivity (85% vs. 77%) though less specificity (88% vs. 91%) than OCBs. Comparatively, IgG index's performance was inferior (AUC 0.83). A decision K index threshold of 2.55 (97% sensitivity) would reduce OCB testing by 52% in the studied population. CONCLUSIONS: The proposed 7.25 cut-off could assist MS diagnostics and identify some false negative cases from OCB studies. Sequential algorithms using K index for the decision to perform OCB detection would improve laboratory efficiency and substantially reduce costs.


Asunto(s)
Esclerosis Múltiple , Biomarcadores , Humanos , Cadenas kappa de Inmunoglobulina/líquido cefalorraquídeo , Laboratorios Clínicos , Esclerosis Múltiple/líquido cefalorraquídeo , Bandas Oligoclonales/líquido cefalorraquídeo
10.
Sci Rep ; 11(1): 12211, 2021 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-34108596

RESUMEN

The broad and heterogeneous clinical spectrum that characterizes common variable immunodeficiency (CVID) is associated with quite different disease course and prognosis, highlighting the need to develop tools that predict complications. We developed a multianalyte VISUAL score (variable immunodeficiency score upfront analytical link) aimed to predict severity using individual CVID patient data at baseline of a cohort of 50 CVID patients from two different centers in Portugal and Spain. We retrospectively applied VISUAL to the CVID clinical severity scores proposed by Ameratunga and Grimbacher after 15 years follow-up of our cohort. VISUAL score at CVID diagnosis showed adequate performance for predicting infectious and non-infectious severe complications (Cluster B). Compared to switched memory B lymphocyte phenotype alone, VISUAL provided a more accurate identification of clinically meaningful outcome, with significantly higher sensitivity (85% vs 55%, p = 0.01), and negative predictive value (77% vs 58%) and AUC of the ROC curves (0.72 vs 0.64), with optimal cut-off level of 10. For every increase of 1 point in the VISUAL scale, the odds of being in the higher risk category (Cluster B) increased in 1.3 (p = 0.005) for Ameratunga's severity score and 1.26 (p = 0.004) for Grimbacher's severity score. At diagnosis of CVID, VISUAL score ≥ 10 showed 8.94-fold higher odds of severe prognosis than below this threshold. Kaplan-Meier estimates for the VISUAL ≥ 10 points showed significantly earlier progression to Cluster B than those with VISUAL < 10 (p = 0.0002). This prognostic laboratory score might allow close monitoring and more aggressive treatment in patients with scores ≥ 10 on a personalized basis approach. Further studies are needed to prospectively validate VISUAL score.


Asunto(s)
Inmunodeficiencia Variable Común/diagnóstico , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Niño , Preescolar , Inmunodeficiencia Variable Común/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Pronóstico , Curva ROC , Estudios Retrospectivos , España/epidemiología , Adulto Joven
11.
Sci Immunol ; 6(64): eabh0891, 2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34623902

RESUMEN

Accumulation of human CD21low B cells in peripheral blood is a hallmark of chronic activation of the adaptive immune system in certain infections and autoimmune disorders. The molecular pathways underpinning the development, function, and fate of these CD21low B cells remain incompletely characterized. Here, combined transcriptomic and chromatin accessibility analyses supported a prominent role for the transcription factor T-bet in the transcriptional regulation of these T-bethighCD21low B cells. Investigating essential signals for generating these cells in vitro established that B cell receptor (BCR)/interferon-γ receptor (IFNγR) costimulation induced the highest levels of T-bet expression and enabled their differentiation during cell cultures with Toll-like receptor (TLR) ligand or CD40L/interleukin-21 (IL-21) stimulation. Low proportions of CD21low B cells in peripheral blood from patients with defined inborn errors of immunity (IEI), because of mutations affecting canonical NF-κB, CD40, and IL-21 receptor or IL-12/IFNγ/IFNγ receptor/signal transducer and activator of transcription 1 (STAT1) signaling, substantiated the essential roles of BCR- and certain T cell­derived signals in the in vivo expansion of T-bethighCD21low B cells. Disturbed TLR signaling due to MyD88 or IRAK4 deficiency was not associated with reduced CD21low B cell proportions. The expansion of human T-bethighCD21low B cells correlated with an expansion of circulating T follicular helper 1 (cTfh1) and T peripheral helper (Tph) cells, identifying potential sources of CD40L, IL-21, and IFNγ signals. Thus, we identified important pathways to target autoreactive T-bethighCD21low B cells in human autoimmune conditions, where these cells are linked to pathogenesis and disease progression.


Asunto(s)
Linfocitos B/inmunología , Receptores de Complemento 3d/inmunología , Proteínas de Dominio T Box/inmunología , Linfocitos T/inmunología , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
Immunol Lett ; 223: 78-88, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32344018

RESUMEN

INTRODUCTION: Given the wide heterogeneity of common variable immunodeficiency (CVID), several groups have proposed clinical and immunological classifications to better define follow-up and prognostic algorithms. The present study aims to validate recent clinical and laboratory algorithms, based on different combinations of CVID biomarkers, to provide more personalized treatment and follow-up strategies. METHODS: We analysed clinical and immunological features of 80 patients with suspected or diagnosed CVID, in two reference centres of Portugal and Spain. Clinical manifestations were categorized into clinical phenotyping proposed by Chapel et al. [1] that included cytopenia; polyclonal lymphocytic infiltration; unexplained enteropathy; and no disease-related complications. RESULTS: 76% of patients in our cohort entered one of the four categories of clinical phenotyping, without overlap (cytopenia; polyclonal lymphocytic infiltration; unexplained enteropathy; and no disease-related complications). The most prominent phenotype was "cytopenia" (40%) followed by "polyclonal lymphocytic infiltration" (19%). The remaining 24% patients of our cohort had overlap of 2 clinical phenotypes (cytopenia and unexplained enteropathy mainly). A delay of CVID diagnosis in more than 6 years presented 3.7-fold higher risk of developing lymphoproliferation and/or malignancy (p < 0.05), and was associated with increased CD8+CD45RO + T-lymphocytes (p < 0.05). An association between decreased switched-memory B cells with lymphoproliferation and malignancy was observed (p < 0.03 and p < 0.05, respectively). CD4 + T-lymphocytopenia correlated with autoimmune phenotype, with 30% prevalence (p < 0.05). HLA-DR7 expression was related to CVID onset in early life in our patients (13 vs 25 years), and DQ2.5 or DQ2.2 with unexplained enteropathy (p < 0.05). CONCLUSIONS: The phenotypic and genetic study is crucial for an adequate clinical orientation of CVID patients. In these two independent cohorts of patients, classification based in clinical and laboratory algorithms, provides more personalized treatment and follow-up strategies.


Asunto(s)
Biomarcadores/metabolismo , Síndromes de Inmunodeficiencia/diagnóstico , Adolescente , Adulto , Anciano , Algoritmos , Niño , Preescolar , Estudios de Cohortes , Diagnóstico Precoz , Femenino , Humanos , Linfopenia , Masculino , Persona de Mediana Edad , Fenotipo , Portugal , Medicina de Precisión , Pronóstico , Estudios Retrospectivos , España , Adulto Joven
13.
J Clin Invest ; 128(9): 3957-3975, 2018 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-29969437

RESUMEN

Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients' neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40phox deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD.


Asunto(s)
Enfermedad Granulomatosa Crónica/genética , Mutación con Pérdida de Función , Fosfoproteínas/deficiencia , Fosfoproteínas/genética , Adolescente , Adulto , Alelos , Niño , Preescolar , Femenino , Técnicas de Inactivación de Genes , Enfermedad Granulomatosa Crónica/diagnóstico , Enfermedad Granulomatosa Crónica/metabolismo , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Linaje , Fagocitos/inmunología , Fagocitos/metabolismo , Fagocitos/microbiología , Fenotipo , Fosfoproteínas/metabolismo , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción Genética , Adulto Joven
14.
Arch. Head Neck Surg ; 51: e20220008, Jan-Dec. 2022.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1401190

RESUMEN

Adenoid cystic carcinoma (ACC) is a rare form of malignant neoplasm of the salivary glands, with slow growth and late symptoms. One of the challenges presented by this tumor is its high rate of metastasis, with tropism to the nervous system, liver and bones. Treatment is based on surgical resection of the tumor, radiotherapy, and chemotherapy ­ it varies depending on the condition of each patient. In view of the low frequency of ACC, this study aims to report a case of ACC in a female patient, with anatomopathological diagnosis of basaloid cell neoplasm

15.
Artículo en Inglés | MEDLINE | ID: mdl-25152759

RESUMEN

Chemotherapy is one of most significant therapeutic approaches to cancer. Immune system functional state is considered a major prognostic and predictive impact on the success of chemotherapy and it has an important role on patients' psychoemotional state and quality of life. In Chinese medicine, chemotherapy is understood as "toxic cold" that may induce a progressive hypofunctional state of immune system, thus compromising the fast recovery of immunity during chemotherapy. In this study, we performed a standardized acupuncture and moxibustion protocol to enhance immunity in cancer patients undergoing chemotherapy and to assess if the improvement of immunity status correlates with a better psychoemotional state and quality of life.

16.
Antioxid Redox Signal ; 21(16): 2231-45, 2014 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-24787605

RESUMEN

AIMS: Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the phagocyte reactive oxygen species (ROS)-producing NOX2 enzyme complex and characterized by recurrent infections associated with hyperinflammatory and autoimmune manifestations. A translational, comparative analysis of CGD patients and the corresponding ROS-deficient Ncf1(m1J) mutated mouse model was performed to reveal the molecular pathways operating in NOX2 complex deficient inflammation. RESULTS: A prominent type I interferon (IFN) response signature that was accompanied by elevated autoantibody levels was identified in both mice and humans lacking functional NOX2 complex. To further underline the systemic lupus erythematosus (SLE)-related autoimmune process, we show that naïve Ncf1(m1J) mutated mice, similar to SLE patients, suffer from inflammatory kidney disease with IgG and C3 deposits in the glomeruli. Expression analysis of germ-free Ncf1(m1J) mutated mice reproduced the type I IFN signature, enabling us to conclude that the upregulated signaling pathway is of endogenous origin. INNOVATION: Our findings link the previously unexplained connection between ROS deficiency and increased susceptibility to autoimmunity by the discovery that activation of IFN signaling is a major pathway downstream of a deficient NOX2 complex in both mice and humans. CONCLUSION: We conclude that the lack of phagocyte-derived oxidative burst is associated with spontaneous autoimmunity and linked with type I IFN signature in both mice and humans.


Asunto(s)
Enfermedad Granulomatosa Crónica/genética , Inmunoglobulina G/inmunología , Interferón-alfa/genética , Interferón beta/genética , NADPH Oxidasas/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/inmunología , Adolescente , Adulto , Animales , Autoinmunidad/inmunología , Niño , Preescolar , Complemento C3/inmunología , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Enfermedad Granulomatosa Crónica/inmunología , Humanos , Interferón-alfa/inmunología , Interferón beta/inmunología , Glomérulos Renales/inmunología , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , Ratones , NADPH Oxidasa 2 , NADPH Oxidasas/inmunología , Adulto Joven
17.
Cad Saude Publica ; 29(11): 2251-60, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24233040

RESUMEN

This study aimed to check for any significant differences in perceived quality of life, specifically aspects of a physical nature, among volunteers who are more physically active and those less physically active in a university community. The sample consisted of 1,966 volunteers in a university community in Brazil. To assess physical activity levels, volunteers responded to the International Physical Activity Questionnaire (IPAQ), and to analyse the perception of quality of life they responded to WHOQOL-bref, which is classified into three groups according to level of physical activity, taking into account the metabolic equivalent index (MET) over a full week. For comparison, consideration was given to the first and third tertiles, respectively, namely groups of more and less active students. The results indicated that individuals who engaged in more physical activity had a more positive perception of quality of life compared to those who were less active in physical aspects related to the ability to work, energy for day-to-day activities and locomotion.


Asunto(s)
Actividad Motora , Calidad de Vida , Adulto , Brasil , Estudios Transversales , Ejercicio Físico/fisiología , Ejercicio Físico/psicología , Femenino , Humanos , Masculino , Encuestas y Cuestionarios , Universidades
18.
Clin Rev Allergy Immunol ; 43(3): 302-7, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22674017

RESUMEN

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by the reactivation of JC virus and occurs in patients with severe primary or secondary immunosuppression. Recently, PML is becoming relevant in autoimmune disorders, particularly in patients treated with biologic agents. However, systemic lupus erythematosus (SLE) appears to be associated with susceptibility to PML that cannot be entirely explained by the immunosuppressive therapy. The authors present two patients with the diagnosis of SLE and PML: One had a heavy immunosuppressive therapy history, and the other had never experienced biologic or cytotoxic therapeutics. Both patients had a profound T-CD4+ lymphopenia during their clinical history. These two cases emphasize the importance of CD4+ lymphopenia in SLE patients with and without immunosuppressors regarding opportunistic infections.


Asunto(s)
Inmunosupresores/inmunología , Leucoencefalopatía Multifocal Progresiva/etiología , Leucoencefalopatía Multifocal Progresiva/inmunología , Lupus Eritematoso Sistémico/etiología , Lupus Eritematoso Sistémico/inmunología , Linfocitopenia-T Idiopática CD4-Positiva/complicaciones , Linfocitopenia-T Idiopática CD4-Positiva/inmunología , Adulto , Femenino , Humanos , Persona de Mediana Edad
19.
Acta Med Port ; 24(5): 833-6, 2011.
Artículo en Portugués | MEDLINE | ID: mdl-22525637

RESUMEN

The Autoimmune Lymphoproliferative Syndrome (ALPS) is an impairment of lymphocyte apoptosis expressed by generalized non-malignant lymphoproliferation, lymphadenopathy and/or splenomegaly. This article describes a seven and 14 year old males. The first one was admitted at 3 years of age with fever, bicytopenia and generalized lymphadenopathy. Hystopathological analysis of lymph nodes showed reactive follicular hyperplasia and marked paracortical expansion. He was readmitted three years later presenting herpes zoster and similar clinical features. High levels of IL-10 and increasing tendency of Fas-L in plasma and serum. The second child was admitted at 13 years of age presenting thigh and gluteus cellulitis, anemia and neutropenia. T lymphocytes aß+CD4-CD8- 3,1%. Hystopathological analysis of lymph nodes showed marked paracortical hyperplasia. Both children are treated with mycophenolate mofetil with good response. ALPS is an underestimated entity that must be considered in non malign lymphoproliferation, autoimmunity and expansion of an unusual population of a/ßCD3+CD4-CD8-(double-negative T cells>1%).


Asunto(s)
Síndrome Linfoproliferativo Autoinmune , Adolescente , Síndrome Linfoproliferativo Autoinmune/diagnóstico , Niño , Humanos , Masculino
20.
Estud. interdiscip. envelhec ; 20(2): 427-440, ago. 2015. tab, graf
Artículo en Inglés | Index Psi Revistas Técnico-Científicas | ID: psi-70151

RESUMEN

Aging has a significant impact on the decrease of lean body mass and physical activity level, being related to the reduction in basal metabolic rate and the increase of overweight and obesity in the elderly. The aim of this study is to identify correlations among the risk factors of metabolic syndrome (MS) from the measurement of abdominal perimeter (AP) and body mass index (BMI) with blood parameters for fasting blood glucose (FBG), total cholesterol (TC) and triglycerides (TG) in active elderly people. Measurements of weight and height were adopted to classify criteria by the World Health Organization (WHO) and to calculate BMI. The measurement of AP was done in centimeters. Blood parameters for FBG, TC, and TG were assessed by collecting blood from the fingertip and analyzing it using the Accutrend Plus (Roche) equipment. For data analysis, the Pearson correlation coefficient between anthropometric measures (independent variables) and blood parameters (dependent variables) was calculated. Simple linear regression was applied to the significant variables (0.05%). The BMI assessment shows 71% of the elderly were overweight and 34% were obese. Over the cut-off point recommended, 57% of the sample was indicated by AP. The correlation test shows evidence regarding the existence of a significant association between FBG and AP and also between AP and TG as compared to the use of BMI. The AP measurement seems to be an efficient indication of the relationship between risk factors for MS and should be incorporated into routines to assess the elderly as an indicator of abdominal obesity. (AU)


O envelhecimento tem um impacto significativo na diminuição de massa magra e do nível de atividade física, estando relacionado à redução na taxa metabólica basal e ao aumento de sobrepeso e obesidade em idosos. O objetivo deste estudo foi identificar correlações entre os fatores de risco da síndrome metabólica (SM) e a medição do perímetro abdominal (PA) e do índice de massa corporal (IMC) com os parâmetros sanguíneos de glicemia de jejum (GJ), colesterol total (CT) e triglicerídeos (TG) em idosos ativos. Para cálculo do IMC, foram coletadas medidas de peso e altura e adotados os critérios de classificação da Organização Mundial da Saúde (OMS). A medida do PA foi efetuada em centímetros. Os parâmetros sanguíneos de GJ, CT e TGL foram avaliados pelo método de coleta de sangue na ponta de dedo com leitura em equipamento Accutrend Plus (Roche). Para análise dos resultados, foi realizado o cálculo do coeficiente de correlação de Pearson entre as medidas antropométricas (variáveis independentes) e parâmetros sanguíneos (variáveis dependentes). A regressão linear simples foi aplicada sobre as variáveis significativas (0.05%). A avaliação do IMC mostrou que 71% dos idosos estavam acima do peso e 34% eram obesos. No ponto de corte recomendado, 57% da amostra foram indicados por PA. O teste de correlação mostrou evidências sobre a existência de uma associação significativa entre GJ e PA e também entre PA e TG em comparação ao uso do IMC. A medição de PA parece seruma indicação eficaz da relação entre os fatores de risco para a SM e deve ser incorporada nas rotinas para avaliar idosos como um indicador de obesidade abdominal. (AU)


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Grasa Abdominal , Síndrome Metabólico/epidemiología , Pruebas Hematológicas , Ejercicio Físico , Factores de Riesgo
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