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1.
Eur Radiol ; 31(3): 1738-1747, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33001310

RESUMO

OBJECTIVES: To assess the combined role of tumor vascularity, estimated from perfusion MRI, and MGMT methylation status on overall survival (OS) in patients with glioblastoma. METHODS: A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships between MGMT and perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored by MGMT methylation in terms of OS. RESULTS: rCBV distributions did not differ significantly (p > 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV < 10.73), MGMT methylation was a positive predictive factor for OS (HR = 2.73, p = 0.003, AUC = 0.70). In patients with highly vascularized tumors (rCBV > 10.73), however, there was no significant effect of MGMT methylation (HR = 1.72, p = 0.10, AUC = 0.56). CONCLUSIONS: Our results indicate the existence of complementary prognostic information provided by MGMT methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from MGMT methylation. Not considering this information may lead to bias in the interpretation of clinical studies. KEY POINTS: • MRI perfusion provides complementary prognostic information to MGMT methylation. • MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile. • Failure to consider these relations may lead to bias in the interpretation of clinical studies.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Humanos , Prognóstico , Regiões Promotoras Genéticas , Temozolomida/uso terapêutico , Proteínas Supressoras de Tumor/genética
2.
Rev Esp Enferm Dig ; 113(4): 269-271, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33233909

RESUMO

BACKGROUND: the autonomic dysfunction defines the neuropathy of the autonomic nervous system. The prevalence of the gastric dysmotility and its relationship with the autonomic dysfunction in patients with alcohol chronic liver disease is not well known. METHODS: thirty-six patients with alcohol chronic liver disease and 25 healthy controls were evaluated, in order to detect an autonomic dysfunction through different cardiovascular reflexes and gastric emptying tests. RESULTS: ninety-four per cent of the patients showed an impaired R index (variations in heart rate during six deep inspirations-expirations per minute) and/or S/S-HR (variations in heart rate when standing from a supine position). Seventy-five per cent of the patients showed gastroparesis (T1/2: gastric half-emptying time was delayed). There was a correlation between the R index and T1/2 (r = -0.49; p < 0.01). CONCLUSIONS: we suggest that gastroparesis detected in alcoholic chronic liver disease is another clinical manifestation of the autonomic parasympathetic dysfunction.


Assuntos
Doenças do Sistema Nervoso Autônomo , Gastroparesia , Hepatopatias , Sistema Nervoso Autônomo , Doenças do Sistema Nervoso Autônomo/etiologia , Esvaziamento Gástrico , Gastroparesia/etiologia , Humanos , Hepatopatias/complicações
3.
Rev. argent. reumatolg. (En línea) ; 31(3): 40-50, set. 2020. ilus, tab
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1149675

RESUMO

Introducción: La artritis reumatoidea se caracteriza por inflamación de la membrana sinovial debido al infiltrado de células inmunitarias que secretan citocinas relacionadas a perfil Th17 como IL-22 e IL-6. La dinámica de estas citocinas durante el tratamiento permanece incomprendida. El objetivo fue evaluar los niveles séricos y en líquido sinovial (LS) de IL-22 e IL-6, correlacionarlos con diferentes parámetros bioquímicos y clínicos y medir sus cambios post-tratamiento. Material y métodos: Se estudiaron 77 pacientes con AR y 30 controles. A 30 pacientes se los evaluó nuevamente luego de 3 meses de tratamiento y a 12 se les extrajo LS. Se midió VSG, PCR, FR, anti-CCPhs, IL-22 e IL-6. Se evaluó la actividad con DAS28 y respuesta al tratamiento con criterios EULAR. Resultados: IL-22 e IL-6 fueron similares entre pacientes y controles. Sus niveles disminuyeron luego del tratamiento, principalmente en pacientes respondedores. IL-22 fue menor e IL-6 mayor en LS que en sangre. IL-6 correlacionó positivamente con PCR y anti-CCPhs. Los niveles de VSG, PCR y DAS28 fueron mayores en pacientes con valores dosables de IL-6 que en no dosables. Conclusión: En pacientes con valores basales dosables de IL-22 e IL-6, los niveles de estas citocinas podrían utilizarse como marcador adicional de respuesta al tratamiento.


Introduction: Rheumatoid arthritis is characterized by synovium inflammation due to the infiltration of immune cells that secrete Th17 cytokines like IL-22 and IL-6. The dynamics of these cytokines during the treatment remain unknown. The aim of this study was to evaluate the levels of IL-22 and IL-6 serum and synovial fluid (SF) in correlation with different biochemical and clinical parameters and treatment-associated changes. Material and methods: Seventy-seven RA patients and 30 controls were recruited. Thirty patients were evaluated after 3 months of treatment and SF was collected of 12 patients. ESR, CRP, RF, anti-CCP hs, IL-22 e IL-6 were measured. DAS28 was used to assess disease activity and response to treatment followed EULAR criteria. Results: There were not differences in serum IL-22 and IL-6 levels between patients and controls. Cytokine levels decreased after treatment, mainly in responder patients. IL-22 was decreased and IL-6 was increased in SF compared to serum. IL-6 correlated positively with CRP and anti-CCPhs. ESR, CRP and DAS28 were increased in patients with detectable IL-6 compared to those with undetectable IL-6. Conclusion: In patients with detectable serum IL-22 and IL-6 levels before treatment initiation, follow-up of cytokine levels could be an useful additional tool to evaluate treatment response.


Assuntos
Artrite Reumatoide , Terapêutica , Interleucinas , Interleucina-6 , Inflamação
4.
Arch. bronconeumol. (Ed. impr.) ; 55(1): 17-22, ene. 2019. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-175187

RESUMO

Objetivos: Analizar las características clinicorradiológicas y del líquido pleural (LP) de los pacientes con derrame pleural tuberculoso (DPT). Métodos: Análisis retrospectivo de los DPT atendidos en nuestro centro durante los últimos 23 años. Resultados: Se estudiaron 320 pacientes con DPT (70% varones; mediana de edad 3 3años). En el 36% de los casos se identificó Mycobacterium tuberculosis en esputo o LP mediante examen microscópico, cultivos en medios sólidos y líquidos, o amplificación de ácidos nucleicos. El mayor porcentaje de identificaciones microbiológicas se relacionó con una co-infección por el virus de la inmunodeficiencia humana (VIH) (OR: 3,27) y con la presencia en LP de unas proteínas < 4g/dl (OR: 3,53), neutrófilos > 60% (OR: 3,23) o glucosa < 40 mg/dl (OR: 3,17). Una adenosina desaminasa pleural < 35 U/l se asoció con DPT que ocupaban < 1/2 del hemitórax (OR: 6,36) y con niveles de lactato deshidrogenasa < 500U/l (OR: 8,09) en LP. Las opacidades pulmonares radiológicas (30%) fueron más comunes si el DPT no alcanzaba la mitad del hemitórax (OR: 2,73), era bilateral (OR: 4,48) o los pacientes tenían mayor edad (OR: 1,02). Los factores predictores de mortalidad fueron: una co-infección VIH (OR: 24), proteínas en LP < 5g/dl (OR: 10) y una mayor edad (OR: 1,05). Conclusiones: Los pacientes con DPT co-infectados por VIH o que presentan concentraciones bajas de proteínas en LP tienen mayor frecuencia de aislamientos microbiológicos y fallecimientos. Asimismo, los pacientes de mayor edad muestran más opacidades pulmonares y mortalidad


Objectives: To analyze the clinical and radiological characteristics and features of pleural fluid (PF) in patients with tuberculous pleural effusion (TPE). Methods: Retrospective analysis of TPEs treated in our clinic over the last 23 years. Results: We included 320 patients with TPE (70% men; median age 33 years). Mycobacterium tuberculosis was identified in the sputum or PF of 36% of the patients by microscopic examination, solid and liquid media cultures, or nucleic acid amplification tests. The greatest percentage of positive microbiological findings were associated with human immunodeficiency virus (HIV) co-infection (OR: 3.27), and with the presence in PF of proteins < 4 g/dL (OR: 3.53), neutrophils > 60% (OR: 3.23), and glucose < 40 mg/dL (OR: 3.17). Pleural adenosine deaminase < 35U/L was associated with TPEs that occupied less than half of the hemithorax (OR: 6.36) and with PF lactate dehydrogenase levels < 500 U/L (OR: 8.09). Radiological pulmonary opacities (30%) were more common in TPE occupying less than half of the hemithorax (OR: 2.73), in bilateral TPE (OR: 4.48), and in older patients (OR: 1.02). Factors predicting mortality were: HIV co-infection (OR: 24), proteins in PF < 5 g/dL (OR: 10), and greater age (OR: 1.05). Conclusions: Patients with TPE and HIV co-infection and those with lower concentrations of proteins in PF had higher rates of positive microbiological results and death. Moreover, older patients had more pulmonary opacities and a higher incidence of death


Assuntos
Humanos , Masculino , Feminino , Adulto , Derrame Pleural , Tuberculose Pleural , Estudos Retrospectivos , Escarro/microbiologia
5.
Arch Bronconeumol (Engl Ed) ; 55(1): 17-22, 2019 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29801681

RESUMO

OBJECTIVES: To analyze the clinical and radiological characteristics and features of pleural fluid (PF) in patients with tuberculous pleural effusion (TPE). METHODS: Retrospective analysis of TPEs treated in our clinic over the last 23years. RESULTS: We included 320 patients with TPE (70% men; median age 33years). Mycobacterium tuberculosis was identified in the sputum or PF of 36% of the patients by microscopic examination, solid and liquid media cultures, or nucleic acid amplification tests. The greatest percentage of positive microbiological findings were associated with human immunodeficiency virus (HIV) co-infection (OR: 3.27), and with the presence in PF of proteins <4g/dL (OR: 3.53), neutrophils >60% (OR: 3.23), and glucose <40mg/dL (OR: 3.17). Pleural adenosine deaminase <35U/L was associated with TPEs that occupied less than half of the hemithorax (OR: 6.36) and with PF lactate dehydrogenase levels <500U/L (OR: 8.09). Radiological pulmonary opacities (30%) were more common in TPE occupying less than half of the hemithorax (OR: 2.73), in bilateral TPE (OR: 4.48), and in older patients (OR: 1.02). Factors predicting mortality were: HIV co-infection (OR: 24), proteins in PF <5g/dL (OR: 10), and greater age (OR: 1.05). CONCLUSIONS: Patients with TPE and HIV co-infection and those with lower concentrations of proteins in PF had higher rates of positive microbiological results and death. Moreover, older patients had more pulmonary opacities and a higher incidence of death.


Assuntos
Derrame Pleural/metabolismo , Tuberculose Pleural , Adenosina Desaminase/análise , Adulto , Fatores Etários , Feminino , Glucose/análise , Infecções por HIV/complicações , Infecções por HIV/mortalidade , Humanos , L-Lactato Desidrogenase/análise , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Neutrófilos , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/microbiologia , Derrame Pleural/mortalidade , Prognóstico , Radiografia Torácica , Estudos Retrospectivos , Escarro/microbiologia , Tuberculose Pleural/diagnóstico por imagem , Tuberculose Pleural/metabolismo , Tuberculose Pleural/microbiologia , Tuberculose Pleural/mortalidade
6.
Case Rep Oncol ; 11(3): 638-647, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30483091

RESUMO

Gastrointestinal bleeding in HIV patients secondary to coinfection by HHV8 and development of Kaposi's sarcoma (KS) is a rare complication even if no skin lesions are detected on physical examination. This article indicates which patients might develop this type of clinical sign and also tries to recall that absence of skin lesions never rules out the presence of KS, especially if gastrointestinal involvement is documented. Gastrointestinal bleeding in terms of hematemesis has rarely been reported in the literature. We review some important clinical findings, diagnosis, and treatment approach. We present the case of an HIV patient who presented to the emergency department with hematemesis and gastrointestinal signs of KS on upper gastrointestinal endoscopy without any dermatological involvement.

7.
Front Immunol ; 9: 2241, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30327652

RESUMO

Background: B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients. Objective: To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy. Methods: Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells. Results: The frequencies of CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1+ B cells (CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24hiCD38hi B cells decreased. CD19+ B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, in vitro, CD8+ T cell proliferation and cytokine production in a PD-L1-dependent manner. Conclusions: Our results show that PD-L1+ B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated in vitro and PD-L1+ B cells could thus provide new perspectives for future treatment strategies.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Linfócitos B Reguladores/efeitos dos fármacos , Linfócitos B Reguladores/imunologia , Antígeno B7-H1/metabolismo , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD19/metabolismo , Artrite Reumatoide/sangue , Antígeno CD24/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Cultivadas , Técnicas de Cocultura , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Estatísticas não Paramétricas , Adulto Jovem
8.
Arthritis Rheumatol ; 70(9): 1429-1439, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29648684

RESUMO

OBJECTIVE: Inhibitory receptors are essential for the regulation of effector immune responses and may play critical roles in autoimmune diseases. We evaluated whether inhibitory receptor expression on T cells from patients with rheumatoid arthritis (RA) were correlated with immune activation, disease activity, and response to treatment, as well as whether inhibitory receptor-mediated pathways were functional. METHODS: Using flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+ and CD8+ T cells from the blood and synovial fluid (SF) of RA patients ex vivo and after culture. The relationship of each parameter with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and response to treatment was examined. RESULTS: In RA patients with low levels of T cell activation, inhibitory receptor expression showed an inverse relationship with the DAS28-ESR. The frequency of T cells expressing multiple inhibitory receptors was reduced in untreated RA patients but returned to normal levels in treated patients. RA patients who responded to treatment showed an augmented frequency of inhibitory receptor-expressing T cells that correlated with reduced inflammatory cytokine production in comparison to nonresponders. Higher frequencies of effector and memory T cells that expressed multiple inhibitory receptors were seen in SF than in peripheral blood. Notably, inhibitory pathways were operative in blood and synovial T cells from all RA patients, although cells from nonresponder patients were less sensitive to inhibition. CONCLUSION: Inhibitory receptor expression on T cells from RA patients is inversely correlated with effector T cell function and disease activity and may predict response to treatment. Furthermore, different inhibitory pathways are functional and cooperatively suppress synovial T cells, providing a rationale for new treatment strategies to regulate acute local inflammation.


Assuntos
Artrite Reumatoide/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Receptores Coestimuladores e Inibidores de Linfócitos T/metabolismo , Índice de Gravidade de Doença , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Biomarcadores/metabolismo , Sedimentação Sanguínea , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Inflamação , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Líquido Sinovial/metabolismo , Adulto Jovem
9.
Reumatol. clín. (Barc.) ; 13(6): 338-343, nov.-dic. 2017. graf
Artigo em Espanhol | IBECS | ID: ibc-167208

RESUMO

Introducción. La artritis reumatoidea (AR) es una enfermedad autoinmune y crónica caracterizada por la presencia de autoanticuerpos como factor reumatoide (FR) y anticuerpos antiproteínas citrulinadas. Una población de células T helper foliculares (Tfh), que expresan CD4+CXCR5+, colabora con las células B para la producción de anticuerpos. La expresión diferencial de CXCR3 y CCR6 dentro de las células CD4+CXCR5+ define 3 subpoblaciones mayores: CXCR3+CCR6− (Tfh1), CXCR3-CCR6− (Tfh2) y CXCR3-CCR6+ (Tfh17). El objetivo del estudio fue evaluar si existe asociación entre el porcentaje de estas células y la AR, y la correlación de las mismas con actividad de la enfermedad. Material y métodos. Participaron 24 pacientes con AR, 22 controles saludables (CS) y 16 pacientes con artritis indiferenciada (AI). Los porcentajes de las células CD4+CXCR5+ y sus subpoblaciones fueron analizados por citometría de flujo. Resultados. No hubo diferencias en los porcentajes de células CD4+CXCR5+ entre los pacientes con AR y CS o entre AR y AI. Tampoco en las subpoblaciones Tfh1, Tfh2 y Tfh17. No hubo correlación entre las células T CD4+CXCR5+, Tfh1, Tfh2 y Tfh17 y el «Disease Activity Score in twenty-eigth joints» (DAS28), así como tampoco con la velocidad de sedimentación globular. Sorpresivamente, hubo una correlación positiva entre las células Tfh17 y la proteína C reactiva. Finalmente, no hubo correlación entre las células TCD4+CXCR5+ o cualquiera de las subpoblaciones y antivimentina mutada citrulinada así como tampoco entre dichas células y el FR. Conclusión. No se hallaron diferencias entre los porcentajes de las células T CD4+CXCR5+ y sus subpoblaciones en sangre periférica de los pacientes con AR y las células de los grupos controles. Esto no descarta un papel patogénico de estas células en el desarrollo y actividad de la AR (AU)


Introduction. Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by the presence of different autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies. CD4T cells expressing CXCR5, referred as follicular helper T cells (Tfh), collaborate with B cells to produce antibodies. Differential expression of CXCR3 and CCR6 within CD4+CXCR5+ T cells defines three mayor subsets: CXCR3+CCR6− (Tfh1), CXCR3-CCR6− (Tfh2) and CXCR3-CCR6+ (Tfh17). The aim of the study was to assess whether there is an association between the percentage of these cells and RA and whether there is a correlation with disease activity. Material and methods. Twenty-four RA patients, 22 healthy controls (HC) and 16 undifferentiated arthritis (UA) patients were included. Percentage of CD4+CXCR5+ T cells and their subsets were analyzed by flow cytometry. Results. No differences were found in the percentages of CD4+CXCR5+ T cells in the comparison of RA vs HC or RA vs UA patients. Tfh1, Tfh2 and Tfh17 subsets showed no differences either. There was no correlation between CD4+CXCR5+T cells, Tfh1, Tfh2 and Tfh17, and Disease Activity Score in twenty-eight joints (DAS28) or erythrocyte sedimentation rate. Surprisingly, there was a positive correlation between Tfh17 cells and C-reactive protein. Finally, there was no correlation between CD4+CXCR5+ T cells, or their subsets, and anti-mutated citrullinated vimentin, or between the cells and RF. Conclusion. There were no differences between the percentages of CD4+CXCR5+ T cells and their subsets in peripheral blood of RA patients and the percentages of cells in the control groups. This finding does not rule out a pathogenic role of these cells in the development and activity of RA (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Citometria de Fluxo/métodos , Estudos de Casos e Controles , Receptores CXCR3/administração & dosagem , Receptores CCR6/administração & dosagem , Autoanticorpos/análise , Antígenos CD4/análise , Estudos Transversais/métodos , Ácido Edético/análise , Imunoensaio/métodos , Análise de Variância , Análise Estatística
10.
Alerg. inmunol. clin ; 36(3/4): 4-10, nov. 2017. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-884602

RESUMO

Estudiamos la influencia del factor de crecimiento endotelial tipo A en pacientes con dermatitis atópica, que es una enfermedad inflamatoria, crónica, recidivante de la piel, que altera la calidad de vida. Se ha visto que el VEGF A podría estar relacionado con la fisiopatología de esta enfermedad. Otro de los objetivos fue determinar el nivel plasmático de Ig E en pacientes enfermos y sanos. Es un estudio clínico, observacional, transversal y analítico en el cual se determinó el valor de VEGF A en suero en 10 paciente con diagnóstico de DA y 10 paciente correspondiente al grupo control. Otras variables estudiadas fueron sexo, edad, antecedentes patológicos alérgicos, antecedentes familiares alérgicos, inicio de la enfermedad, sintomatología mucocutánea, síntomas sistémicos acompañante, valores de Ig E sérica total, pruebas de Prick test, pruebas de hipersensibilidad retardada Parches Cutáneos. Se analizó el VEGF-A sérico mediante inmunoensayo enzimático siguiendo las instrucciones del fabricante (Human VEGF-A Platinum) ELISA. Como conclusión en este trabajo se pudo observar que no hubo relación con el aumento de VEGF A sérico en pacientes con DA, probablemente porque se produzca en región local de la lesión inflamatoria. Se requiere un mayor estudio para su análisis.


We studied the influence of endothelial growth factor type A on patients with atopic dermatitis, which is an inflammatory, chronic, recurrent disease of the skin, which alters the quality of life. It has been shown that VEGF A may be related to the pathophysiology of this disease. Another objective was to determine the plasma level of IgE in sick and healthy patients. It is a clinical, observational, transversal and analytical study in which the value of VEGF A in serum was determined in 10 patients with diagnosis of AD and 10 patients corresponding to the control group. Other variables were sex, age, allergic pathological history, allergic family history, onset of disease, mucocutaneous symptomatology, accompanying systemic symptom, total serum IgE values, Prick test, delayed hypersensitivity tests Skin Patches. Serum VEGF- A was analyzed by enzyme immunoassay following the manufacturer's instructions (Human VEGF-A Platinum) ELISA. As conclusion, in this work it was observed that there was no relationship with the increase of serum VEGF A in patients with AD probably because it occurs in the local region of the inflammatory lesion. Further study is required for analysis.

11.
Reumatol Clin ; 13(6): 338-343, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27595364

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by the presence of different autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies. CD4T cells expressing CXCR5, referred as follicular helper T cells (Tfh), collaborate with B cells to produce antibodies. Differential expression of CXCR3 and CCR6 within CD4+CXCR5+ T cells defines three mayor subsets: CXCR3+CCR6- (Tfh1), CXCR3-CCR6- (Tfh2) and CXCR3-CCR6+ (Tfh17). The aim of the study was to assess whether there is an association between the percentage of these cells and RA and whether there is a correlation with disease activity. MATERIAL AND METHODS: Twenty-four RA patients, 22 healthy controls (HC) and 16 undifferentiated arthritis (UA) patients were included. Percentage of CD4+CXCR5+ T cells and their subsets were analyzed by flow cytometry. RESULTS: No differences were found in the percentages of CD4+CXCR5+ T cells in the comparison of RA vs HC or RA vs UA patients. Tfh1, Tfh2 and Tfh17 subsets showed no differences either. There was no correlation between CD4+CXCR5+T cells, Tfh1, Tfh2 and Tfh17, and Disease Activity Score in twenty-eight joints (DAS28) or erythrocyte sedimentation rate. Surprisingly, there was a positive correlation between Tfh17 cells and C-reactive protein. Finally, there was no correlation between CD4+CXCR5+ T cells, or their subsets, and anti-mutated citrullinated vimentin, or between the cells and RF. CONCLUSION: There were no differences between the percentages of CD4+CXCR5+ T cells and their subsets in peripheral blood of RA patients and the percentages of cells in the control groups. This finding does not rule out a pathogenic role of these cells in the development and activity of RA.


Assuntos
Artrite Reumatoide/sangue , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adulto , Anticorpos Anti-Proteína Citrulinada/sangue , Artrite Reumatoide/imunologia , Sedimentação Sanguínea , Proteína C-Reativa/análise , Estudos de Casos e Controles , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Receptores CCR6/análise , Receptores CXCR3/análise , Subpopulações de Linfócitos T/química , Linfócitos T Auxiliares-Indutores/química , Células Th17/química , Células Th17/imunologia , Vimentina/imunologia
12.
J Zoo Wildl Med ; 46(3): 553-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26352960

RESUMO

In 2012, 543 harbor seals (Phoca vitulina) and 124 grey seals (Halichoerus grypus) were admitted to the Seal Rehabilitation and Research Centre in Pieterburen, The Netherlands. In 19 seals (3%), signs of infection in a hind flipper were observed. Initial treatment consisting of antibiotics and anti-inflammatory drugs resolved the symptoms in 15 animals. In four harbor seals, estimated to be 3 to 4 mo old, a necrotizing infection developed that resulted in osteoarthritis of the tarsus or tibiotarsal joint or both. Bacterial culture revealed the presence of polymicrobial infection in three of the four animals. Treatment consisted of amputation of the hind flipper under general anesthesia combined with tumescent anesthesia in the operation field. Amputations were done at the diaphysis of the tibia and fibula. After resecting these bones, the flipper was discarded, leaving a good muscle-skin cuff to cover the edges of the bones and close the skin without tension. The estimated blood loss varied between <50 to 150 ml. Healing was uneventful, and both antibiotics and analgesics were gradually reduced according to the individual response. The seals did not show any functional impairment 1 mo postoperatively. After release to the sea, scrutinous revision of all radiographs showed signs of osteomyelitis in at least one animal in the proximal part of the tibia, also present preoperatively. It is concluded that tumescent anesthesia in seals may reduce perioperative blood loss and that a lower leg amputation is a surgically easy and clean approach for the treatment of osteoarthritis of the hind flipper of seals, giving good functional results (diving, catching fish, exiting a pool, and moving on land).


Assuntos
Amputação/veterinária , Infecções Bacterianas/veterinária , Membro Posterior/patologia , Osteoartrite/veterinária , Phoca , Animais , Antibacterianos/uso terapêutico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Membro Posterior/cirurgia , Osteoartrite/microbiologia , Osteoartrite/cirurgia
13.
MAbs ; 4(4): 488-96, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22647435

RESUMO

The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the stable expression and biological evaluation of an anti-CD20 biosimilar antibody. While rituximab is produced in fed-batch culture of recombinant Chinese hamster ovary (CHO) cells, our biosimilar antibody expression process consists of continuous culture of recombinant murine NS0 myeloma cells. The ability of the purified biosimilar antibody to recognize the CD20 molecule on human tumor cell lines, as well as on peripheral blood mononuclear cells from humans and primates, was demonstrated by flow cytometry. The biosimilar antibody induced complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and apoptosis on human cell lines with high expression of CD20. In addition, this antibody depleted CD20-positive B lymphocytes from peripheral blood in monkeys. These results indicate that the biological properties of the biosimilar antibody compare favorably with those of the innovator product, and that it should be evaluated in future clinical trials.


Assuntos
Anticorpos Monoclonais Murinos/imunologia , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos/imunologia , Antígenos CD20/imunologia , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Murinos/genética , Anticorpos Monoclonais Murinos/farmacologia , Afinidade de Anticorpos/imunologia , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Antígenos CD20/genética , Antígenos CD20/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Células CHO , Linhagem Celular Tumoral , Células Cultivadas , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Cricetinae , Cricetulus , Citotoxicidade Imunológica/efeitos dos fármacos , Citotoxicidade Imunológica/imunologia , Citometria de Fluxo , Humanos , Células K562 , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Macaca fascicularis , Engenharia de Proteínas/métodos , Rituximab
14.
MAbs ; 4(3): 398-402, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22531446

RESUMO

Multispecificity is not a well-understood property of some antibodies. Different functions have been attributed to multispecific natural antibodies, commonly associated with the neutralization and clearance of antigens. Much less is known about the role of antibodies like these, based on their idiotypic connectivity. B7Y33 is a chimeric IgG1 version of a polyreactive α anti-idiotype antibody that is able to interact with different immunoglobulin and non-immunoglobulin antigens. Here we report the capacity of this antibody to enhance the immunogenicity of several autologous IgMs in adjuvant-free conditions. Our results suggest that the formation of immune complexes seems to be necessary, but not sufficient, to this activity. The potential involvement of the interaction of B7Y33 with the FcγRIIb is discussed.


Assuntos
Anticorpos Anti-Idiotípicos/uso terapêutico , Imunoglobulina G/uso terapêutico , Imunoterapia , Receptores de IgG/metabolismo , Proteínas Recombinantes de Fusão/uso terapêutico , Anticorpos Anti-Idiotípicos/imunologia , Autoantígenos/imunologia , Epitopos , Humanos , Imunoglobulina G/imunologia , Imunomodulação , Ligação Proteica , Proteínas Recombinantes de Fusão/imunologia
15.
Immunobiology ; 216(12): 1239-47, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21802167

RESUMO

Gangliosides containing the N-glycolyl (NGc) form of sialic acid are tumor-associated antigens and promising candidates for cancer therapy. We previously generated the murine 14F7 monoclonal antibody (mAb), specific for the N-glycolyl-GM3 ganglioside (NGcGM3), which induced an oncosis-like type of cell death on malignant cell lines expressing this antigen and recognized breast carcinoma by immunoscintigraphy in cancer patients. As humanization is expected to enhance its use for human cancer therapy, herein we describe the design and generation of two humanized versions of the 14F7 mAb by disrupting potential human T cell epitopes on its variable region. No differences in antigen reactivity or cytotoxic properties were detected among the variants tested and with respect to the chimeric counterpart. Humanized 14F7 genes were transfected into the NGcGM3-expressing NS0 cell line. Therefore, in the industrial scaling-up of the transfectoma in serum-free medium, cell viability was lost due to the cytotoxic effect of the secreted antibody. This shortcoming was solved by knocking down the CMP-N-acetylneuraminic acid hydroxylase enzyme, thus impairing the synthesis of NGc-glycoconjugates. Humanized 14F7 mAb is of potential value for the therapy of NGcGM3-expressing tumors.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antígenos de Neoplasias/imunologia , Neoplasias da Mama/tratamento farmacológico , Gangliosídeo G(M3)/imunologia , Imunoterapia , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Anticorpos Monoclonais Humanizados/genética , Anticorpos Monoclonais Humanizados/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Citotoxicidade Imunológica/genética , Epitopos de Linfócito T/genética , Feminino , Gangliosídeo G(M3)/análogos & derivados , Humanos , Hibridomas , Camundongos , Oxigenases de Função Mista/genética , Terapia de Alvo Molecular , Mutagênese Sítio-Dirigida , Engenharia de Proteínas , RNA Interferente Pequeno/genética
16.
Mol Immunol ; 48(8): 1059-67, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21306777

RESUMO

Gangliosides are sialic acid-containing glycosphingolipids present in the plasma membrane of most mammalian cells. In humans, the expression of the N-glycolylated (Neu5Gc) variant of the sialic acid has been associated with malignant transformation, constituting therefore an attractive target for cancer immunotherapy. P3 monoclonal antibody (mAb) recognizes Neu5Gc-containing gangliosides, as well as sulfatides. Heavy chain CDR3 (H-CDR3) arginine residues have been shown to be crucial for ganglioside recognition, but less important for anti-idiotypic antibody binding. Here, we describe the effect on antibody reactivity of different mutations involving a single H-CDR3 acid residue. Substitution of glutamate 99 (Kabat numbering) by arginine, aspartate or serine residues resulted in no differences in anti-idiotype binding. However, the first mutation caused increased reactivity with the antigen, including a cytotoxic effect of the antibody on ganglioside-expressing cells previously unseen for the wild type antibody. Another antibody that recognizes N-glycolyl-GM3 ganglioside (GM3(Neu5Gc)), but not other glycolipids, named 14F7, exhibits also an arginine-enriched H-CDR3 and a complement-independent cell death activity. Unlike 14F7 mAb, the cytotoxicity of the P3 E(99)→R mutant antibody did not exclusively depend on ganglioside expression on tumor cells.


Assuntos
Anticorpos Monoclonais/imunologia , Gangliosídeo G(M2)/imunologia , Gangliosídeo G(M3)/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Mutação , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Regiões Determinantes de Complementaridade/genética , Regiões Determinantes de Complementaridade/imunologia , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Idiótipos de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Camundongos , Dados de Sequência Molecular , Ligação Proteica/imunologia
17.
Rev Alerg Mex ; 58(4): 192-9, 2011.
Artigo em Espanhol | MEDLINE | ID: mdl-24007829

RESUMO

BACKGROUND: Allergic rhinitis and asthma are the most common chronic inflammatory diseases affecting the respiratory tract. A subgroup of regulatory T cells, CD4+CD25+, participates in the control of allergic diseases. OBJETIVE: To determine if there is a difference in the number of peripheral blood regulatory T cells, identified as CD4+CD25+CD127low, of patients with rhinitis compared to healthy controls; if there is correlation of the number of these cells with other manifestations of the disease and if that number changes in the same individual after immunotherapy. METHODS: In 37 patients with allergic rhinitis CD4+CD25+CD127low T cells were quantified by flow cytometry, percentages of eosinophils in blood and nasal secretions were determined in smear, total serum IgE concentrations were measured by ELISA and serum PCR concentrations using a immunoturbidimetric assay. RESULTS: At baseline the percentage of CD4+CD25+CD127low T cells was higher in patients than in controls (8.031 ± 1.507 vs. 7.316 ± 1.309, p = 0.03). After a year of immunotherapy, the number of regulatory T cells did not show any significant difference respect to the initial value (7.39 ± 1.43 vs. 7.36 ± 1.22; p = 0.9387). The number of regulatory T cells after a year of immunotherapy showed correlation with the eosinophils percentage in nasal secretion (r = 0.7178, p = 0.0234). CONCLUSIONS: The number of regulatory T cells in allergic rhinitis is increased probably due to induced generation in response to the chronic inflammation of the nasal mucosa.


Assuntos
Subunidade alfa de Receptor de Interleucina-2 , Linfócitos T Reguladores , Contagem de Células , Fatores de Transcrição Forkhead , Humanos , Imunoterapia , Rinite Alérgica
18.
Mol Immunol ; 48(1-3): 98-108, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20952071

RESUMO

Detailed information on the immunological relevance of α-type anti-idiotypic antibodies is lacking after more than 30 years since Jerne postulated his Idiotypic Network Theory. The B7Y33 mutant is a mouse-human chimeric version of the B7 MAb, a polyreactive α-type anti-idiotypic antibody, generated against an anti-GM2 ganglioside IgM Ab1 antibody. It retained the unusual self-binding activity and multispecificity of the parental murine antibody, being able to recognize several anti-ganglioside IgM antibodies as well as non-immunoglobulin antigens. Previous work with the murine B7 MAb suggested that this antibody might have immunoregulatory properties, and therefore we investigated the possible interaction of B7Y33 with immune cells. We found that B7Y33 binds to human and murine B lymphocytes. Inhibition assays using flow cytometry indicated that this antibody is capable of binding the Fc γ receptor II (FcγRII). The recognition of FcγRII-expressing K562, Raji and Daudi human cell lines, together with the capability of inhibiting the binding of an anti-human FcγRII antibody to these cells, suggest that B7Y33 interacts with both the FcγRIIa and FcγRIIb isoforms. We evaluated the contribution to the binding of different surface-exposed residues at the top of the heavy chain variable region (VH) CDR loops through the construction of mutants with substitutions in the three conventional VH CDRs (HCDRs) and the "HCDR4", located in the framework 3 (HFR3). In addition, we assessed the involvement of the Fc region by performing key mutations in the CH2 domain. Furthermore, chimeric hybrid molecules were obtained by combining the B7Y33 heavy chain with unrelated light chains. Our results indicate that the multispecificity and self-binding properties of B7Y33 are not linked to its recognition of B lineage cells, and that this phenomenon occurs in a non-classical way with the participation of both the variable and constant regions of the antibody. Two possible models for this interaction are proposed, with B7Y33 binding to two FcγRIIb molecules through the Fc and Fv regions, or simultaneously to FcγRIIb and another unknown antigen on B cells. The FcγRIIb has recently received great attention as an attractive target for therapies directed to B lymphocytes. The recognition of peripheral B lymphocytes from B cell chronic lymphocytic leukemia (B-CLL) patients by B7Y33 suggests its potential application for the treatment of B cell malignancies.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Especificidade de Anticorpos/imunologia , Linfócitos B/imunologia , Receptores de IgG/imunologia , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos/genética , Linhagem Celular , Separação Celular , Regiões Determinantes de Complementaridade/genética , Regiões Determinantes de Complementaridade/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Receptores de IgG/genética
19.
Rev. neurol. (Ed. impr.) ; 51(3): 129-134, 1 ago., 2010. tab
Artigo em Espanhol | IBECS | ID: ibc-86703

RESUMO

Introducción. La extensa aplicación de estudios de resonancia magnética (RM) conlleva un aumento en la detección de alteraciones de la sustancia blanca del sistema nervioso central. Objetivo. Investigar la evolución de pacientes sin síntomas neurológicos previos, con hallazgos de RM altamente sugestivos de esclerosis múltiple (EM). Pacientes y métodos. Estudio descriptivo de once pacientes con RM sugestiva de EM. Mediante seguimiento longitudinal se determinaron la progresión radiológica y la conversión a síndrome neurológico aislado y EM clínicamente definida. Resultados. Se identificó a 11 pacientes (7 mujeres y 4 varones), con una edad media de 36 años (rango: 28-48 años), sometidos a RM por cefalea (n = 2), prolactinoma (n = 2), radiculalgia (n = 3), traumatismo craneoencefálico (n = 1), síncope (n = 1), patología nerviosa periférica (n = 1) y crisis epiléptica (n = 1). El número medio de criterios Barkhof-Tintoré en la RM inicial fue de 3. El estudio de bandas oligoclonales fue positivo en 6 casos y en 9 pacientes se realizaron potenciales evocados visuales (3 patológicos). El seguimiento medio fue de 2,9 años (rango: 2 meses-11,9 años). El tiempo medio entre la primera y la segunda RM fue de 2,03 años. Se identificó una progresión radiológica en 7 casos (5 de ellos con captación de gadolinio). Cinco pacientes convirtieron a síndrome neurológico aislado, con un tiempo medio desde la RM inicial de 4,13 años. De ellos, tres pacientes presentaron conversión a EM clínicamente definida, dos en forma recurrenteremitente (tras 8,54 años de media desde la RM inicial) y otro en forma primaria progresiva. Conclusión. La identificación de lesiones incidentales altamente sugestivas de EM podría ayudar a constituir un grupo de sujetos con riesgo aumentado de desarrollar EM (AU)


Introduction. The widespread application of magnetic resonance imaging (MRI) has brought with it an increase in the detection of alterations in the white matter of the central nervous system. Aim. To investhighly suggestive of multiple sclerosis (MS). Patients and methods. We conducted a descriptive studigate the evolution of patients with no previous neurological symptoms, but in whom MRI findings are y of 11 patients with MRI findings suggesting MS. A longitudinal follow-up was used to determine the radiological progression and conversion into an isolated neurological syndrome and clinically defined MS. Results. Eleven patients (seven females and four males) were identified, with a mean age of 36 years (range: 28-48 years), who had been submitted to an MRI scan due to headache (n = 2), radiculalgia (n = 3), traumatic brain injury (n = 1), syncope (n = 1), peripheral nervous pathology (n = 1) and epileptic seizures (n = 1). The mean number of Barkhof-Tintoré criteria in the initial MRI scan was three. The oligoclonal band study was positive in six cases and in nine patients visual evoked potentials were performed (three pathological). The mean follow-up time was 2.9 years (range: 2 months-11.9 years). The mean amount of time elapsed between the first and the second MRI scan was 2.03 years. A radiological progression was identified in seven cases (five of them with gadolinium uptake). Five patients became cases of isolated neurological syndrome, with a mean amount of time since the initial MRI scan of 4.13 years. Of these, three patients presented conversion into clinically defined MS, two into the relapsing-remitting form (after an average of 8.54 years since the initial MRI scan) and another into the primary progressive form (AU)


Assuntos
Humanos , Doenças Desmielinizantes/diagnóstico , Esclerose Múltipla/diagnóstico , Doenças do Sistema Nervoso/complicações , Achados Incidentais , Espectroscopia de Ressonância Magnética/métodos
20.
Rev Neurol ; 51(3): 129-34, 2010 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-20645263

RESUMO

INTRODUCTION: The widespread application of magnetic resonance imaging (MRI) has brought with it an increase in the detection of alterations in the white matter of the central nervous system. AIM. To investigate the evolution of patients with no previous neurological symptoms, but in whom MRI findings are highly suggestive of multiple sclerosis (MS). PATIENTS AND METHODS: We conducted a descriptive study of 11 patients with MRI findings suggesting MS. A longitudinal follow-up was used to determine the radiological progression and conversion into an isolated neurological syndrome and clinically defined MS. RESULTS: Eleven patients (seven females and four males) were identified, with a mean age of 36 years (range: 28-48 years), who had been submitted to an MRI scan due to headache (n = 2), radiculalgia (n = 3), traumatic brain injury (n = 1), syncope (n = 1), peripheral nervous pathology (n = 1) and epileptic seizures (n = 1). The mean number of Barkhof-Tintore criteria in the initial MRI scan was three. The oligoclonal band study was positive in six cases and in nine patients visual evoked potentials were performed (three pathological). The mean follow-up time was 2.9 years (range: 2 months-11.9 years). The mean amount of time elapsed between the first and the second MRI scan was 2.03 years. A radiological progression was identified in seven cases (five of them with gadolinium uptake). Five patients became cases of isolated neurological syndrome, with a mean amount of time since the initial MRI scan of 4.13 years. Of these, three patients presented conversion into clinically defined MS, two into the relapsing-remitting form (after an average of 8.54 years since the initial MRI scan) and another into the primary progressive form. CONCLUSIONS: The identification of incidental lesions that are highly suggestive of MS could help to constitute a group of subjects with an increased risk of developing MS.


Assuntos
Encéfalo/patologia , Doenças Desmielinizantes/patologia , Achados Incidentais , Imageamento por Ressonância Magnética/métodos , Adulto , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/patologia
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