Navegando por Palavras-chave "Antibodies"

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    Abordagens inovadoras para o desenvolvimento de vacinas
    (Universidade Federal de São Paulo, 2021-01-29) Carrieri, Carolina Roberto [UNIFESP]; Xander, Patricia [UNIFESP]; http://lattes.cnpq.br/3620553457348403; http://lattes.cnpq.br/1892792741999704
    O sistema imunológico é capaz de eliminar corpos estranhos, como patógenos, para manter a homeostasia do corpo. Contudo, alguns desses patógenos são capazes de escapar dos mecanismos das respostas imunológicas. Por isso, a vacinação foi desenvolvida e utilizada para imunizar as pessoas contra doenças. Entretanto, a vacinação ainda não é uma prática sustentável contra qualquer patógeno. Doenças como AIDS e malária ainda permanecem sem vacinas. Por isso, novas técnicas estão sendo estudadas como alternativas para a produção de vacinas seguras e eficazes contra doenças que os métodos convencionais não abrangem. Este estudo tem o objetivo de discutir sobre as principais técnicas que têm se mostrado promissoras nesse processo de desenvolvimento de vacinas para melhor compreensão do atual quadro de pesquisas e o que a tecnologia conseguiu proporcionar até hoje. Foi realizada revisão bibliográfica de estudos publicados em plataformas científicas a partir do ano de 2010. As técnicas de obtenção de vacina mantidas como promissoras em seus estudos clínicos foram selecionadas e são devidamente apresentadas neste trabalho, a saber: desenvolvimento a partir de ácidos nucleicos, vetores virais, nanopartículas e vesículas extracelulares. O desenvolvimento deste estudo possibilitou visualizar o quadro atual das pesquisas dessas tecnologias, em qual estágio de estudo cada uma se encontra, a fim de entender melhor seus mecanismos, vantagens e desvantagens.
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    Antibodies as Crypts of Antiinfective and Antitumor Peptides
    (Bentham Science Publ Ltd, 2009-06-01) Magliani, W.; Conti, S.; Cunha, Rodrigo Luiz Oliveira Rodrigues [UNIFESP]; Travassos, Luiz Rodolpho [UNIFESP]; Polonelli, L.; Univ Parma; Universidade Federal de São Paulo (UNIFESP); Dept Microbiol Imunol & Parasitol
    Antibodies (Abs), often associated with antimicrobial and antitumor agents, have emerged as an important class of novel drugs for antigen-driven therapeutic purposes in diverse clinical settings, including oncology and infectious diseases. Abs commonly give rise in the treated host to anti-Ab responses, which may induce adverse reactions and limit their therapeutic efficacy. Their modular domain architecture has been exploited to generate alternative reduced formats (Fabs, scFvs, dAbs, minibodies, multibodies), essentially devoid of the Fc region. The presence of complementarity determining regions (CDRs) ensures the maintenance of selective binding to antigens and supports their use for biotechnological and therapeutic applications. Paradigmatic Abs mimicking the wide-spectrum antimicrobial activity of a yeast killer toxin (killer Abs) have revealed the existence of a family of Abs exerting a direct in vitro and/or in vivo microbicidal activity. Based on the variable sequence of an antiidiotypic recombinant killer Ab, CDR-related peptides have been synthesized, engineered by alanine-scanning and selected according to antimicrobial, antiviral and immunomodulatory properties. Irrespective of the native Ab specificity, synthetic CDRs from unrelated murine and human monoclonal Abs, have shown to display differential in vitro, in vivo and/or ex vivo antifungal (Candida albicans), antiviral (HIV-1) and antitumor (melanoma cells) activities. Alanine substitution of single residues of synthetic CDR peptides resulted in further differential increased/unaltered/decreased biological activity. The intriguing potential of Abs as source of antiinfective and antitumor therapeutics will be discussed, in light of recent advances in peptide design, stability and delivery.
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    Antibodies to intimin and Escherichia coli-secreted proteins EspA and EspB in sera of Brazilian children with hemolytic uremic syndrome and healthy controls
    (Elsevier B.V., 2013-03-15) Guirro, Mirian [UNIFESP]; Souza, Renato Lopes de [UNIFESP]; Piazza, Roxane M. F.; Guth, Beatriz E. C. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Inst Butantan
    Enterohemorrhagic Escherichia coli (EHEC) strains can cause hemolytic uremic syndrome (HUS), a leading cause of childhood renal failure. the adhesin intimin and the secreted proteins A (EspA) and B (EspB) contribute to the occurrence of EHEC attaching and effacing lesions. in this study, immunoblot assays were performed to determine immunoglobulin G (IgG) antibodies reactive with these proteins in sera from 13 children diagnosed with HUS and in sera from 54 healthy Brazilian children. in general, high frequencies of serum IgG antibodies reactive with EspA, EspB and the conserved region of intimin were observed in both HUS patients and controls with no statistically significant differences. However, a marked difference in immune response to these proteins was observed in HUS patients compared to controls in infants less than two years of age. in addition, IgG against the variable region of intimin was more frequently detected in HUS patients than in children with no signs of infection (p < 0.05) regardless of age, suggesting that the detection of antibodies directed to the variable region of intimin gamma can be useful in serodiagnostic tests of EHEC-infected patients. the immune response against intimin and structural proteins encoded by the locus of enterocyte effacement pathogenicity island in patients with HUS has previously not been described in Brazil. the results presented here may contribute to the development of diagnostic tools and complement information concerning EHEC epidemiology in our setting. (C) 2012 Elsevier B.V. All rights reserved.
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    Anticorpos monoclonais
    (Universidade Federal de São Paulo, 2021-02-05) Conceição, Ana Beatriz Alves da [UNIFESP]; Xander, Patricia [UNIFESP]; http://lattes.cnpq.br/3620553457348403; http://lattes.cnpq.br/6687689950877389
    Anticorpos monoclonais (mAbs) são moléculas de imunoglobulinas idênticas produzidas para um antígeno específico. Anticorpos são estruturalmente compostos por 2 cadeias leves e 2 cadeias pesadas que contém o sítio de ligação ao antígeno e a região que se liga à receptores das células do sistema imunológico. O primeiro anticorpo monoclonal foi produzido em 1975 com a técnica de produção de hibridoma, onde há fusão de uma célula de mieloma com uma célula B de um animal previamente imunizado. Porém, anticorpos murinos apresentam diferenças em relação aos anticorpos humanos e, por isso, foram relatadas reações de hipersensibilidade e rápida eliminação do organismo, comprometendo sua função terapêutica. Desde então, várias técnicas surgiram com o objetivo de aumentar a segurança e eficácia do mAbs. Essas técnicas incluem: anticorpos humanizados e quiméricos, produzidos pela tecnologia de DNA recombinante, por Phage Display, ou animais transgênicos; e anticorpos monoclonais humanos, produzidos por tecnologia de célula B única. Atualmente, há mais de 80 anticorpos monoclonais aprovados para a clínica, sendo a maior parte deles para tratamento de doenças, como câncer. Neste trabalho, foi realizada revisão bibliográfica com o objetivo de identificar e discutir as principais técnicas para obtenção de anticorpos monoclonais e suas aplicações.
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    Anticorpos séricos contra doenças preveníveis através de imunização em adolescentes atendidos no Ambulatório de Adolescentes da Universidade Federal de São Paulo
    (Universidade Federal de São Paulo (UNIFESP), 2004) Dinelli, Maria Isabel Saraiva [UNIFESP]; Moraes-Pinto, Maria Isabel de [UNIFESP]
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    Avaliação da suplementação com L-glutamina sobre a modulação do perfil inflamatório e dos níveis de IgA salivares e séricas em idosos vacinados contra o vírus Influenza
    (Universidade Federal de São Paulo (UNIFESP), 2021) Paixao, Vitoria Da [UNIFESP]; Vaisberg, Mauro Walter [UNIFESP]; Universidade Federal de São Paulo
    Background: Although glutamine has demonstrated the capacity to improve immunity, its action on the immune response, both systemic and in the upper airways, in elderly subjects is unclear. Therefore, we aimed to evaluate the L-glutamine supplementation effect on the response of cytokines and immunoglobulin A, both systemic and present in the airway mucosa, in elderly people vaccinated against the Influenza virus. Methods: Saliva and blood sampling from 83 physically active elderly were collected pre and post 30 days after Influenza virus vaccination and also supplementation with L-glutamine (Gln, n=42) or placebo (PL, n=41). It was evaluated the salivary levels of the pro [interleukin (IL) 6, IL-17, and tumor necrosis factor (TNF-α) and anti inflammatory (IL-10 and IL-37) cytokines, as well as the total and specific immunoglobulin A secretory (IgAs) for the vaccine against the Influenza virus. In addition, vaccine-specific serum IgA levels were also assessed. Results: Higher serum levels of specific-IgA were observed in both groups post-vaccination as compared to pre-vaccination values. In relation to the response in the mucosa, higher levels of IL-17 and IgAs, both total and specific for the vaccine, were found post vaccination in the Gln group compared to the values observed pre-vaccination and in the PL group after vaccination. In addition, higher salivary levels of IL-6 and IL-10 were observed post-vaccination in the Gln group than pre-vaccination values, while lower levels of IL-37 were found post-vaccination in both groups as compared to the pre vaccination values. TNF-α levels were unchanged. Positive correlations between IL-6 and IL-10 were found in the two volunteer groups pre and post-vaccination and also between IL-17 and IL-6 or IL-10 in the Gln group post-vaccination. A negative correlation between IL-37 and IL-10 was found pre- and post-vaccination in the PL group. Conclusion: In this study we were able to demonstrate, for the first time, that Gln supplementation modulates mucosal immunity, through IgAs and cytokines, improving the response to vaccination against the influenza virus in the elderly subjects.
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    Cellular and humoral immune responses against the Plasmodium vivax MSP-1(19) malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil
    (Biomed Central Ltd, 2013-09-16) Riccio, Evelyn K. P.; Totino, Paulo R. R.; Pratt-Riccio, Lilian R.; Ennes-Vidal, Vitor; Soares, Irene S.; Rodrigues, Mauricio Martins [UNIFESP]; Souza, Jose Maria de; Daniel-Ribeiro, Claudio Tadeu; Ferreira-da-Cruz, Maria de Fatima; Fiocruz MS; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); SVS
    Background: Plasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen considered to be one of the leading malaria vaccine candidates. PvMSP-1 is highly immunogenic and evidences suggest that it is target for protective immunity against asexual blood stages of malaria parasites. Thus, this study aims to evaluate the acquired cellular and antibody immune responses against PvMSP-1 in individuals naturally exposed to malaria infections in a malaria-endemic area in the north-eastern Amazon region of Brazil.Methods: the study was carried out in Paragominas, Para State, in the Brazilian Amazon. Blood samples were collected from 35 individuals with uncomplicated malaria. Peripheral blood mononuclear cells were isolated and the cellular proliferation and activation was analysed in presence of 19 kDa fragment of MSP-1 (PvMSP-1(19)) and Plasmodium falciparum PSS1 crude antigen. Antibodies IgE, IgM, IgG and IgG subclass and the levels of TNF, IFN-gamma and IL-10 were measured by enzyme-linked immunosorbent assay.Results: the prevalence of activated CD4(+) was greater than CD8(+) T cells, in both ex-vivo and in 96 h culture in presence of PvMSP-1(19) and PSS1 antigen. A low proliferative response against PvMSP-1(19) and PSS1 crude antigen after 96 h culture was observed. High plasmatic levels of IFN-gamma and IL-10 as well as lower TNF levels were also detected in malaria patients. However, in the 96 h supernatant culture, the dynamics of cytokine responses differed from those depicted on plasma assays; in presence of PvMSP-1(19) stimulus, higher levels of TNF were noted in supernatant 96 h culture of malaria patient's cells while low levels of IFN-gamma and IL-10 were verified. High frequency of malaria patients presenting antibodies against PvMSP-1(19) was evidenced, regardless class or IgG subclass. PvMSP-1(19)-induced antibodies were predominantly on non-cytophilic subclasses.Conclusions: the results presented here shows that PvMSP-1(19) was able to induce a high cellular activation, leading to production of TNF and emphasizes the high immunogenicity of PvMSP-1(19) in naturally exposed individuals and, therefore, its potential as a malaria vaccine candidate.
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    Detection of hepatitis A antibodies by ELISA using saliva as clinical samples
    (Instituto de Medicina Tropical, 2000-08-01) Oba, Isabel Takano; Spina, Angela Maria Miranda; Saraceni, Cláudia Patara; Lemos, Marcílio Figueiredo; Senhoras, Rita De Cássia Ferreira Andrade; Moreira, Regina Célia; Granato, Celso Francisco Hernandes [UNIFESP]; Instituto Adolfo Lutz Department of Virology; Health Center; Universidade Federal de São Paulo (UNIFESP)
    The possibility of detecting acute infection and immunity using body fluids that are easier to collect than blood, mainly in children, would facilitate the investigation and follow-up of outbreaks of hepatitis A (HAV). Our study was carried out to evaluate the detection of anti-HAV IgM, IgA and total antibodies in saliva using serum samples as reference. Forty three paired serum and saliva samples were analyzed. From this total, 24 samples were obtained from children and 1 from one adult during the course of acute hepatitis A; an additional 18 samples were obtained from health professionals from Adolfo Lutz Institute. The sensitivity to detect anti-HAV IgM was 100% (95%CI: 79.1 to 100.0%), employing saliva as clinical samples. In detecting anti-HAV IgA, the sensitivity was 80.8% (95%CI: 60.0 to 92.7%) and for the total antibodies was 82.1% (95%CI: 62.4 to 93.2%). The specificity was 100% for each. The rate of agreement was high comparing the results of serum and saliva samples for detecting HAV antibodies. We conclude that saliva is an acceptable alternative specimen for diagnosing acute hepatitis A infection, and for screening individuals to receive hepatitis A vaccine or immunoglobulin.
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    Doença de Chagas: aspectos gerais e imunopatogenia com foco para a atuação das células B-1 durante a infecção - uma revisão bibliográfica
    (Universidade Federal de São Paulo, 2022-12-07) Queiroz, Júlia Fonseca [UNIFESP]; Batista, Patricia Xander [UNIFESP]; http://lattes.cnpq.br/3620553457348403
    A doença de Chagas é uma zoonose negligenciada causada pelo protozoário Trypanosoma cruzi, que apresenta grande importância epidemiológica e que nos últimos anos tem se disseminado para fora da área endêmica. Ainda há diversos questionamentos acerca da imunopatogenia da doença de Chagas e a relação parasita-hospedeiro. Estudos realizados demonstram que é muito importante o balanço entre citocinas pró- e anti-inflamatórias para uma resposta imunológica mais efetiva ao parasito, mas não só isso, os efeitos protetivos dependem do background genético do hospedeiro, da virulência da cepa e do inóculo, o que denota grande desafio para o desenvolvimento de novas terapias. Diversos estudos já demonstraram que pacientes na fase crônica exibem anticorpos autorreativos que levam a piora do quadro clínico, mas ainda não se sabe como esses anticorpos são gerados. As células B-1, ainda pouco estudadas, dentre diversas funcionalidades, são capazes de produzir citocinas e anticorpos, incluindo autoanticorpos. Na fase aguda da doença de Chagas os anticorpos aparecem com baixa especificidade e podem perdurar durante longos períodos em mecanismo similar ao que acontece no lúpus eritematoso sistêmico, o que levanta o questionamento sobre a implicação desses anticorpos na evolução da doença. Na fase crônica, uma maior frequência de células B-1 e seu perfil anti-inflamatório parecem ser favoráveis para o hospedeiro. O presente estudo pretende conectar os aspectos gerais da doença de Chagas e a sua imunopatogenia, com foco para a atuação células B-1 durante a infecção, mesmo que poucos estudos tenham sido realizados acerca das implicações dessas células na patologia em questão. Essas células têm papel relevante na doença de Chagas e podem ser protagonistas ou mesmo direcionadoras para o desenvolvimento de novas estratégias terapêuticas no combate a T. cruzi se mais esforços forem realizados para estudá-las no contexto dessa parasitose.
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    Efeitos bioquímicos e imunológicos da terapia anti-hipertensiva
    (Universidade Federal de São Paulo (UNIFESP), 2009) Brandão, Sergio Augusto Bueno [UNIFESP]; Fonseca, Francisco Antonio Helfenstein [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objetivos: Lipoproteínas oxidadas e anticorpos (Abs) anti-LDL oxidada (antiLDLox) foram detectados no plasma em resposta à elevação da pressão arterial, sugerindo a participação do sistema imune adaptativo. Postulamos que o tratamento da hipertensão possa modificar a resposta imune diminuindo o estímulo oxidativo. Analisamos os títulos de Abs anti-LDLox após adequado controle da hipertensão arterial. Métodos: Títulos de Abs anti-LDLox foram examinados em pacientes com hipertensão arterial no estágio 1 (n=94), sem manifestação clínica prévia de aterosclerose ou fatores de risco clássicos para a doença coronariana e isentos de medicações anti-hipertensivas. Pacientes foram distribuídos aleatoriamente para terapia com perindopril, hidroclorotiazida ou indapamida por 12 semanas, com adição de perindopril, se necessário para adequado controle pressórico. Títulos de Abs anti-LDLox foram mensurados por ELISA. Resultados: O tratamento anti-hipertensivo reduziu as pressões arteriais casuais e as obtidas pela MAPA (p<0,0005), diminuiu os níveis plasmáticos de substâncias reativas ao ácido tiobarbitúrico (p<0,05) e aumentou os títulos dos Ab anti-LDLox (p<0,005) e a dilatação mediada pelo fluxo (p<0,0005), independentemente do tratamento instituído. Conclusões: Aumento nos títulos de Abs anti-LDLox após terapia anti-hipertensiva ao lado de melhor função endotelial e diminuição do estresse oxidativo sugerem que a despeito de maior estímulo oxidativo estar presente na hipertensão, os Abs anti-LDLox podem ser potenciais biomarcadores protetores para monitorizar o tratamento da hipertensão.
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    Hepatitis B vaccine - proposal for a standardized assessment of immune response
    (Instituto de Medicina Tropical, 1992-04-01) Ferraz, Maria Lucia Cardoso Gomes [UNIFESP]; Silva, Antonio Eduardo Benedito [UNIFESP]; Yamamoto, Marico [UNIFESP]; Guimaråes, Rubens Xavier [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The authors developed a comparative study of the various methods of assessment of immune response to Hepatitis B vaccine. Eighty-six health care professionals underwent a vaccination programme with three doses of plasma-derived vaccine against Hepatitis B (H-B-Vax, Merck, Sharp & Dohme) given intra-muscularly. Assessment of immune response was carried out three months after the end of the programme, by radioimmunoassay (RIA) and enzymeimmunoassay (EIA). The results showed that the semi-quantitative assessment of Anti-HBs antibodies by RIA or EIA was perfectly comparable to the reference method (quantitative determination of antibodies by RIA). In view of these findings, the authors suggest a standardization of assessment of immune response to the vaccine, thus permitting correct planning of booster doses and easier comparison between different studies
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    High circulating autoantibodies against human oxidized low-density lipoprotein are related to stable and lower titers to unstable clinical situation
    (Elsevier B.V., 2009-08-11) Santos, Andreza O. [UNIFESP]; Fonseca, Francisco A. H. [UNIFESP]; Fischer, Simone M. [UNIFESP]; Monteiro, Carlos M. C. [UNIFESP]; Brandao, Sergio A. B. [UNIFESP]; Povoa, Rui M. S. [UNIFESP]; Bombig, Maria T. N. [UNIFESP]; Carvalho, Antonio C. [UNIFESP]; Monteiro, Andrea M. [UNIFESP]; Ramos, Eduardo [UNIFESP]; Gidlund, Magnus; Figueiredo Neto, Antonio M. [UNIFESP]; Izar, Maria C. O. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Background: Oxidized lipoproteins and antibodies anti-oxidized low-density lipoprotein (anti-oxLDL) have been detected in human plasma and in atherosclerotic lesions. However, the role of these autoantibodies in the maintenance of vascular health or in the pathogenesis of acute vascular insults remains unclear. We examined the relationship of human immunoglobulin G (IgG) anti-oxLDL antibodies with cardiovascular disease risk markers in stable subjects and in patients after an acute coronary syndrome (ACS).Methods: Titers of human anti-oxLDL antibodies were measured in hypertensive subjects in primary prevention (n = 94), without other risk factors, and in individuals after a recent ACS event who also had metabolic syndrome (n = 116). Autoantibodies against copper ion oxidized LDL were measured by enzyme-linked-immunosorbent assay.Results: Anti-oxLDL titers were higher in hypertensive patients and these subjects presented lower high sensitivity C-reactive protein (hs-CRP) than those with ACS (p < 0.0001). We found significant correlations between anti-oxLDL and hs-CRP (r = -0.284), body mass index (r = -0.256), waist circumference (r = -0.368), apolipoprotein B (r = -0.191), glucose (r = -0.303), systolic blood pressure (r = 0.319), diastolic blood pressure (r = 0.167), high-density lipoprotein cholesterol (r = 0.224) and apolipoprotein A1 (r = 0.257) (p < 0.02 for all). After multiple linear regression hs-CRP, fasting glucose and waist circumference remained independently and inversely associated with anti-oxLDL.Conclusions: Acute inflammatory and metabolic conditions decrease titers of human antibodies of IgG class against oxidized LDL, and that circulating anti-oxLDL antibodies could be associated with a protective role in atherosclerosis. (C) 2009 Elsevier B.V. All rights reserved.
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    Hormone replacement therapy increases levels of antibodies against heat shock protein 65 and certain species of oxidized low density lipoprotein
    (Associação Brasileira de Divulgação Científica, 2003-04-01) Uint, Luciana; Gebara, Otávio Celso Eluf; Pinto, Lígia B.; Wajngarten, Maurício; Boschcov, Paulo [UNIFESP]; Luz, Protásio Lemos da; Gidlund, Magnus; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Hormone replacement therapy (HRT) reduces cardiovascular risks, although the initiation of therapy may be associated with transient adverse ischemic and thrombotic events. Antibodies against heat shock protein (Hsp) and oxidized low density lipoprotein (LDL) have been found in atherosclerotic lesions and plasma of patients with coronary artery disease and may play an important role in the pathogenesis of atherosclerosis. The aim of the present study was to assess the effects of HRT on the immune response by measuring plasma levels of antibodies against Hsp 65 and LDL with a low and high degree of copper-mediated oxidative modification of 20 postmenopausal women before and 90 days after receiving orally 0.625 mg equine conjugate estrogen plus 2.5 mg medroxyprogesterone acetate per day. HRT significantly increased antibodies against Hsp 65 (0.316 ± 0.03 vs 0.558 ± 0.11) and against LDL with a low degree of oxidative modification (0.100 ± 0.01 vs 0.217 ± 0.02) (P<0.05 and P<0.001, respectively, ANOVA). The hormone-mediated immune response may trigger an inflammatory response within the vessel wall and potentially increase plaque burden. Whether or not this immune response is temporary or sustained and deleterious requires further investigation.
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    Immunohistochemical analysis of retinoblastoma cell phenotype using neuronal and glial cell markers
    (Consel Brasil Oftalmologia, 2016) Orellana, Maria Eugenia; Belfort, Rubens Neto [UNIFESP]; Antecka, Emilia; Burnier Júnior, Miguel Noel Nascente [UNIFESP]
    Purpose: The cellular origin of retinoblastoma is uncertain as constituent tumor cells heterogeneously express markers of both immature and mature retinal cells. An immunohistochemical analysis of cellular origin may yield valuable insights into disease progression and treatment options. This study aimed to determine the cellular origin of retinoblastoma in a large case series and correlate these findings with histopathological prognostic factors. Methods: Thirty-nine retinoblastoma cases were histopathologically diagnosed and analyzed by immunohistochemistry using monoclonal antibodies against the immature neural cell marker SRY-box containing gene 2 (SOX-2), the mature neuronal cell marker microtubule-associated protein 2 (MAP2), and the mature glial cell marker glial fibrillary acidic protein (GFAP). Histopathological features were also evaluated, including patterns of growth, differentiation, vitreous see-ding, and choroidal/scleral, optic nerve, and anterior chamber invasion. Two retinoblastoma cell lines, WERI-1 and Y79, were studied by immunocytochemistry using the same antibodies. Results: Expression of SOX-2 was strong in 97.4% of retinoblastoma cases, while MAP-2 was expressed in 59% of cases. Immunostaining for GFAP was positive only in reactive stromal astrocytes interspersed amongst tumor cells and in peritumoral tissue. There was no correlation between histopathological prognostic factors and immunohistochemical markers. Retinoblastoma cell lines showed strong positivity for SOX2 (90% of WERI-1 cells and 70% of Y79 cells) and MAP2 (90% of cells in both lines). GFAP was completely negative in both cell lines. Conclusion: The majority of retinoblastomas and both RB cell lines expressed an immature neural and/or a mature neuronal cell marker, but not a glial marker. These results indicate a typical neuroblast or neuronal origin and eliminate astrocyte differentiation from neural stem cells as the source of retinoblastoma.
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    Imunodeficiência e ativação imune no lupus eritematoso sistêmico juvenil, na infecção e na exposição vertical ao vírus da imunodeficiência humana
    (Universidade Federal de São Paulo (UNIFESP), 2009-06-24) Miyamoto, Maristela [UNIFESP]; Moraes-Pinto, Maria Isabel de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introdução: O uso da terapia de alta potência tem aumentado a sobrevida dos pacientes infectados pelo HIV e permitido uma reconstituição imune desses indivíduos. A avaliação dessa reconstituição imune e suas consequências são de especial relevância para crianças e adolescentes. Métodos: Avaliamos 41 crianças e adolescentes infectados, com idade de 6 a 21 anos e 25 crianças e adolescentes sadios não expostos ao HIV, com idade semelhante (Controle). O grupo HIV foi dividido em HIV Indetectável (Carga Viral <400cópias/mL) e HIV Detectável (Carga Viral>400cópias/mL). Foi realizada imunofenotipagem dos linfócitos, incluindo avaliação de ativação imune e apoptose através de CD38 QuantiBRITE e caspase-3 ativa, respectivamente. Imunoglobulinas (IgA, IgG, IgM) e anticorpos contra sarampo e tétano também foram avaliados. Resultados: Pacientes infectados pelo HIV apresentaram menor expressão de CD28 em células T em relação aos indivíduos do grupo Controle (CD4+CD28+ - Controle: 98.3%. vs. HIV Indetectável: 96.3%. Tukey, p=0.02. CD8+CD28+ - Controle: 70.4%, HIV Indetectável: 56.7%, HIV Detectável: 50.3%. Controle vs. HIV Indetectável e Controle vs. HIV Detectável. Tukey, p=0.01 para ambas comparações). A média de CD38/célula T CD8+ foi mais elevada no HIV Detectável quando comparado com HIV Indetectável e Controle (Controle: 1725.8, HIV Indetectável: 1638.5, HIV Detectável: 3502.0. Controle vs. HIV Indetectável e Controle vs. HIV Detectável. Tukey, p=0.01 para ambas comparações). HIV Detectável teve níveis de apoptose mais elevados em células T CD8+ do que o HIV Indetectável (HIV Indetectável: 4.8% vs. HIV Detectável: 10.2%. Tukey, p=0.03). Os grupos HIV tiveram menores títulos de anticorpos contra sarampo e tétano do que o grupo Controle (Sarampo – Controle: 0.86 UI/mL vs. HIV Detectável: 0.05 UI/mL. Tukey. p=0.01. Tétano: Controle: 0.88 UI/mL vs. HIV Detectável: 0.14 UI/mL. Tukey. p=0.03). Conclusões: Mesmo após uso da terapia de alta potência, crianças e adolescentes infectados pelo HIV mantêm ativação imune e apoptose de células T CD8+, assim como baixa expressão de CD28, o que pode contribuir para uma baixa resposta a antígenos vacinais
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    Microdensidade vascular no leito placentário em pacientes portadoras de Pré-eclâmpsia: estudo transversal descritivo comparativo
    (Universidade Federal de São Paulo (UNIFESP), 2006-03-29) Coelho, Tarcisio Mota [UNIFESP]; Sass, Nelson [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    CONTEXT AND OBJECTIVE Morphological changes in the spiral arteries of the placental bed have been studied in patients with preeclampsia one of de most cause of maternal and perinatal morbidly and mortality. According to the reports, vasospasm and vascular endothelial injury are two major pathological conditions of preeclampsia. OBJECTIVE: The aim of the study was to investigate microvessel density of spiral arteries in the placental bed in pregnancies complicated by hypertension and proteinuria as well as in normal pregnancy. DESIGN AND SETTING: A cross-sectional survey of imunohistochemical study using CD 34, of placental bed biopsies containing spiral arteries based on women undergoing caesarean sections for clinical and obstetrical reasons performed at the Universidade Federal de São Paulo, São Paulo, Brazil. METHODS: Placental bed biopsies were obtained during caesarean section after placental removal, under direct visualization of central area of placental insertion and measurement of microvessel density spiral arteries by immunohistochemical in decidual and miometrial segments, using antibody CD34. RESULTS: Biopsies containing spiral arteries were obtained from 34 hypertensive pregnant women with proteinuria, and 26 normotensive pregnant women. Microvessel density in decidual and miometrial segments of placental bed was compared in both groups. It was observed that, with the increase of blood pressure and proteinuria, microvessel density dropped gradually. CONCLUSION: The presence and elevations of high levels of hypertension and proteinuria may
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    Molecular characterization and intracellular distribution of the alpha 5 subunit of Trypanosoma cruzi 20S proteasome
    (Elsevier B.V., 2009-12-01) Gutierrez, Bessy; Osorio, Luis; Motta, Maria Cristina M.; Huima-Byron, Telervo; Erdjument-Bromage, Heydeie; Munoz, Christian; Sagua, Hernan; Mortara, Renato A. [UNIFESP]; Echeverria, Alex; Araya, Jorge E.; Gonzalez, Jorge; Univ Antofagasta; Universidade Federal do Rio de Janeiro (UFRJ); New York Blood Ctr; Mem Sloan Kettering Canc Ctr; Universidade Federal de São Paulo (UNIFESP); N Catholic Univ
    Three different monoclonal antibodies were produced against Trypanosona cruzi proteasomes. These antibodies were shown to react with a single 27-kDa hand on immunoblots of purified proteasomes. Using a 7E5 monoclonal antibody (IgG1) that recognized the alpha 5 subunit of protozoan protease we have studied the intracellular distribution of the T cruzi 20S proteasome. Contrary to all cell types described to date, T cruzi 20S proteasome was found not only in the cytoplasm and nucleus but also in the kinetoplast. As revealed by confocal microscopy, the reactivity of monoclonal antibody 7E5 was highly specific for protozoan proteasome because the antibody recognized only the proteasomes from parasites and not those from the mammalian host in T. cruzi infected cells. These findings were confirmed by immunoblots or immunoprecipitations, followed by chymotrypsin-like activity detection in kinetoplasts isolated by differential centrifugation and sucrose density gradients. Proteasome 20S was present in all T cruzi stages and only slight differences in terms of relative abundance were found. the potential role of the proteasome in kinetoplast remodeling remains to be determined. (C) 2009 Published by Elsevier Ireland Ltd.
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    Mucin-like molecules form a negatively charged coat that protects Trypanosoma cruzi trypomastigotes from killing by human anti-alpha-galactosyl antibodies
    (Company Of Biologists Ltd, 2000-04-01) Pereira-Chioccola, Vera Lucia [UNIFESP]; Serrano, Alvaro Acosta; Almeida, Igor Correia de [UNIFESP]; Ferguson, Michael AJ; Souto-Padron, Thais Cristina; Rodrigues, Mauricio Martins [UNIFESP]; Travassos, Luiz Rodolpho [UNIFESP]; Schenkman, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Inst Dante Pazzanese Cardiol Estado Sao Paulo; Johns Hopkins Univ; Univ Dundee; Universidade Federal do Rio de Janeiro (UFRJ)
    In the presence of sialic acid donors Trypanosoma cruzi acquires up to 10(7) sialic acid residues on its surface, in a reaction catalyzed by its unique trans-sialidase. Most of these sialic acid residues are incorporated into mucin-like glycoproteins. To further understand the biological role of parasite sialylation, we have measured the amount of mucin in this parasite, We found that both epimastigote and trypomastigote forms have the same number of mucin molecules per surface area, although trypomastigotes have less than 10% of the amount of glycoinositol phospholipids, the other major surface glycoconjugate of T. cruzi, Based on the estimated surface area of each mucin, we calculated that these molecules form a coat covering the entire trypomastigote cell, The presence of the surface coat is shown by transmission electron microscopy of Ruthenium Red-stained parasites, The coat was revealed by binding of antibodies isolated from Chagasic patients that react with high affinity to a-galactosyl epitopes present in the mucin molecule, When added to the trypomastigote, these antibodies cause an extensive structural perturbation of the parasite coat with formation of large blebs, ultimately leading to parasite lysis, Interestingly, lysis is decreased if the mucin coat is heavily sialylated, Furthermore, addition of MgCl2 reverses the protective effect of sialylation, suggesting that the sialic acid negative charges stabilize the surface coat, Inhibition of sialylation by anti-trans-sialidase antibodies, found in immunized animals, or human Chagasic sera, also increase killing by anti-a-galactosyl antibodies, Therefore, the large amounts of sialylated mucins, forming a surface coat on infective trypomastigote forms, have an important structural and protective role.
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    Padronização da técnica de neutralização para quantificação de anticorpos dirigidos contra poliovírus empregando vírus vacinais
    (Universidade Federal de São Paulo (UNIFESP), 2010-11-24) Lima, Elaine dos Santos [UNIFESP]; Granato, Celso Francisco Hernandes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Even after many decades of efforts to eradicate poliomyelitis this disease is still endemic in some Asian and African countries, representing a threat to all other countries due to international travels. Recently new measures to control viral stocks of poliovirus have been proposed to the health community. Among these the use of wild strains of polio in testing can compromise WHOs aim of absolute poliomyelitis virus eradication. The present study proposes to change the present methodology for one adapted test using vaccine viruses. For this, we used the oral vaccine Sabin and HEp-2 neutralization methodology. We tested 64 samples from patients sera previously titrated antibodies from wild poliovirus strains, considered the gold standard. Results of neutralization with vaccine strains were compared and the parameters were calculated as sensitivity, specificity, prevalence, accuracy, positive predictive value and negative predictive value for the three viral serotypes. Results showed a very close approximation between the results with the vaccine strain and the gold standard. We conclude that this evaluation demonstrates a good performance of the alternative diagnostic procedure, confirmed the immune status of the patients, and provides a great alternative to replace the wild type strain. Thus, we minimize the risks in laboratory procedures, to continue to perform the serological diagnosis of polio, especially in immunocompromised patients and transplant recipients.