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1.
J Laryngol Otol ; 131(7): 614-619, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28502258

RESUMO

BACKGROUND: Eustachian tube dysfunction is a poorly defined condition associated with various symptoms and it can predispose to middle-ear disease. Balloon dilation Eustachian tuboplasty has been proposed as a treatment for Eustachian tube dysfunction. OBJECTIVE: To evaluate the subjective and objective outcomes of balloon dilation Eustachian tuboplasty in patients with recurrent, previously treated chronic Eustachian tube dysfunction. METHODS: The study was conducted on 11 patients (13 ears) who had undergone previous unsuccessful medical and surgical treatment. Tympanometry was the primary outcome measure. Secondary outcome measures included pure tone audiogram assessment and seven-item Eustachian Tube Dysfunction Questionnaire score. RESULTS: Balloon dilation Eustachian tuboplasty resulted in significant improvements in 11 patients' subjective but not objective outcome measures. CONCLUSION: The objective abnormality and subjective symptoms in Eustachian tube dysfunction may represent two distinct pathological processes, which may nevertheless influence and exacerbate each other.


Assuntos
Dilatação/métodos , Otopatias/terapia , Tuba Auditiva , Adulto , Cateterismo/métodos , Otopatias/diagnóstico , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Resultado do Tratamento
2.
J Med Life ; 6(3): 244-8, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-24155782

RESUMO

Respiratory diseases are responsible for a significant number of deaths and considerable suffering in humans. Accumulating evidence suggests that oral disorders, particularly periodontal disease, may influence the course of respiratory infections like bacterial pneumonia and chronic obstructive pulmonary disease (COPD). Oral periodontopathic bacteria can be aspirated into the lung causing aspiration pneumonia. The teeth may also serve as a reservoir for respiratory pathogen colonization and subsequent nosocomial pneumonia. The overreaction of the inflammatory process that leads to the destruction of the connective tissue is present in both periodontal disease and emphysema. This overreaction may explain the association between periodontal disease and chronic obstructive pulmonary disease. The mechanisms of infection could be the aspiration into the lung of oral pathogens capable of causing pneumonia, colonization of dental plaque by respiratory pathogens followed by aspiration, or facilitation of colonization of the upper airway by pulmonary pathogens by periodontal pathogens. The present article briefly reviews the epidemiologic evidence & role of periodontopathogens in causing respiratory infections.


Assuntos
Doenças Periodontais/complicações , Doenças Periodontais/microbiologia , Doenças Respiratórias/etiologia , Doenças Respiratórias/microbiologia , Citocinas/metabolismo , Humanos , Aspiração Respiratória/complicações , Aspiração Respiratória/microbiologia , Mucosa Respiratória/microbiologia , Mucosa Respiratória/patologia , Fatores de Risco
3.
Clin Exp Immunol ; 172(2): 217-27, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23574318

RESUMO

Nuclear factor (NF)-κB is a transcription factor implicated in the pathogenesis of autoimmune disorders such as rheumatoid arthritis (RA). Here we have examined the effect of intra-articular administration of the IKK inhibitor, NEMO-binding domain peptide (NBD), on the severity of collagen-induced arthritis (CIA). NBD peptides were injected intra-articularly into the knee joints of DBA/1J mice after the onset of disease. Collagen-injected mice given a scrambled peptide served as controls. Arthritis severity was determined by visual examination of paws. Intra-articular NBD injection reduced the arthritis score and ameliorated morphological signs of bone destruction compared to the controls. Serum levels of type-II collagen-specific immunoglobulin (Ig)G2a antibodies were lower in NBD-treated mice versus the control mice, whereas the levels of type-II collagen-specific IgG1 antibodies were increased by NBD treatment. NBD treatment diminished the proinflammatory cytokines interleukin (IL)-17 and interferon (IFN)-γ in serum, but increased the regulatory cytokine IL-10. NBD-treated CIA mice exhibited significantly higher percentages and numbers of forkhead box protein 3 (FoxP3(+)) CD4(+) CD25(+) regulatory T cells than controls. Immunofluorescence analysis of NBD-treated mice revealed that FoxP3 and Ym1, a marker of alternatively activated macrophages, were juxtaposed to each other within draining inguinal lymph nodes. Intra-articular administration of NBD peptide is effective as an experimental therapy in a murine model of RA. Nevertheless, the intra-articular treatment modality is still associated with systemic effects on the immune system.


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Macrófagos/imunologia , NF-kappa B/antagonistas & inibidores , Linfócitos T Reguladores/imunologia , Animais , Artrite Experimental/metabolismo , Autoimunidade , Antígenos CD4/biossíntese , Colágeno , Fatores de Transcrição Forkhead/biossíntese , Imunoglobulina G/imunologia , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-17/biossíntese , Subunidade alfa de Receptor de Interleucina-2/biossíntese , Lectinas , Ativação Linfocitária , Ativação de Macrófagos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos DBA , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Linfócitos T Reguladores/metabolismo , beta-N-Acetil-Hexosaminidases
4.
J Contemp Dent Pract ; 13(4): 571-3, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23151712

RESUMO

UNLABELLED: Fluorosis can cause enamel degeneration to varying extent depending on the fluoride levels prevalent in that particular area. It can range from slight mottling of enamel to severe degeneration leading to demineralization and resultant discoloration. In the latter case, treatment options are limited to bonding of the outer surface of teeth either with composite or porcelain. CLINICAL SIGNIFICANCE: Porcelain laminates offer an excellent solution to enhance esthetics in a patient with fluorosis as it combines the advantage of being highly esthetic along with being conservative in its penetration to enamel.


Assuntos
Porcelana Dentária/uso terapêutico , Facetas Dentárias , Fluorose Dentária/terapia , Humanos , Masculino , Preparo Prostodôntico do Dente , Adulto Jovem
5.
J Contemp Dent Pract ; 13(1): 80-4, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22430699

RESUMO

The present study was undertaken to assess the skeletal craniofacial asymmetry in South Indian population by a posteroanterior cephalometric radiographic method. The skeletal craniofacial structures on one side of the face were compared with that of the other, by drawing various triangles representing different craniofacial regions. The sample consisted of 60 subjects (30 males and 30 females) aged between 18 to 25 years, who were mainly dental college students from South India. Overall 52 X-rays were obtained, with four errors each in the male and the female groups. The results revealed that the total facial structures in the South Indian population were larger on the left side (statistically insignificant). The cranial base area exhibited a greater degree of asymmetry than any other component area of the face, which might be due to the inaccuracy at the condylar point.


Assuntos
Cefalometria/métodos , Assimetria Facial/diagnóstico , Ossos Faciais/patologia , Crânio/patologia , Adolescente , Adulto , Queixo/patologia , Oclusão Dentária Central , Feminino , Humanos , Incisivo/patologia , Índia , Masculino , Mandíbula/patologia , Côndilo Mandibular/patologia , Processo Mastoide/patologia , Dente Molar/patologia , Osso Nasal/patologia , Sela Túrcica/patologia , Adulto Jovem , Zigoma/patologia
6.
J Dent Res ; 91(2): 142-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21876032

RESUMO

Cigarette smoke (CS) causes considerable morbidity and mortality by inducing cancer, chronic lung and vascular diseases, and oral disease. Despite the well-recognized risks associated with smoking, the habit remains unacceptably prevalent. Several toxins present in CS have immunomodulatory effects. CS also contains trace amounts of microbial cell components, including bacterial lipopolysaccharide. These and other CS constituents induce chronic inflammation at mucosal surfaces and modify host responses to exogenous antigens. The effects of CS on immunity are far-reaching and complex; both pro-inflammatory and suppressive effects may be induced. The net effect of CS on immunity depends on many variables, including the dose and type of tobacco, the route and chronicity of exposure, and the presence of other factors at the time of immune cell stimulation, such as Toll receptor ligands or other inflammatory mediators. CS impairs innate defenses against pathogens, modulates antigen presentation, and promotes autoimmunity. CS also impairs immunity in the oral cavity and promotes gingival and periodontal disease and oral cancer. The recognition of specific mechanisms by which CS affects host immunity is an important step toward elucidating mechanisms of tobacco-induced disease and may identify novel therapeutic approaches for the management of diseases that afflict smokers.


Assuntos
Fumar/imunologia , Apresentação de Antígeno/imunologia , Autoimunidade/imunologia , Misturas Complexas/imunologia , Humanos , Imunidade nas Mucosas/imunologia , Fatores Imunológicos/imunologia , Imunossupressores/imunologia , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Doenças da Boca/imunologia , Neoplasias Bucais/imunologia , Doenças Periodontais/imunologia , Toxinas Biológicas/imunologia
7.
Child Care Health Dev ; 31(6): 703-6, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16207228

RESUMO

BACKGROUND: We have previously reported the developmental gains achieved, after introducing a simple programme of structured play to stimulate children in an orphanage. It was envisaged that the caregivers could continue the programme. However, the enthusiasm of the caregivers waned over the year the programme was entrusted to them. After 1 year, a full time play therapist was recruited to rejuvenate the play programme. METHODS: Children's development was assessed using the Indian adaptation of the Bayley Scales of Infant Development. The first assessment was done when the play therapist joined. Subsequently, three-monthly assessments were done and the scores achieved were recorded. RESULTS: The initial mean motor and mental scores, when the play therapist joined, were 66.14 and 56.95, respectively (similar to the pre-intervention scores of the pilot study reported in an earlier paper). The scores improved to 81.84 and 78.25 within 3 months of restarting the play programme. CONCLUSION: The schedule of the 'Not by Bread Alone' project can accelerate the motor and mental development of children in orphanages. However, it requires a highly motivated and dedicated person to sustain this programme over long periods.


Assuntos
Desenvolvimento Infantil , Orfanatos , Ludoterapia/métodos , Atitude Frente a Saúde , Criança Institucionalizada/psicologia , Pré-Escolar , Humanos , Lactente , Inteligência , Destreza Motora/fisiologia
8.
Cell Mol Biol (Noisy-le-grand) ; 49(2): 193-207, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12887102

RESUMO

Autoantibodies directed against variable domain epitopes of the alpha/beta T cell receptor (TCR) occur in sera of man, mouse and other vertebrates. Here, we focus upon autoantibodies expressed in human rheumatoid arthritis (RA) and systemic erythematosus (SLE) with parallel studies involving collagen induced arthritis (CIA) in mice transgenic for human HLA-DR conferring resistance or susceptibility to autoimmune disease. We report specificity characterization of polyclonal and monoclonal IgM and IgG autoantibodies from SLE and for IgM monoclonal autoantibodies of RA patients. The data suggests that autoantibodies directed against "public" idiotopes present in the first complementarity determining region (CDR1) and the third framework (FR3) of the Vbeta gene products are generated in response to over-production of autodestructive T cells bearing particular Vbeta gene products and function to modulate (downregulate) the expression of these T cells. Since antibodies of these specificities are present in polyclonal IgG immunoglobulin (IVIG) preparations used for therapeutic purposes, the immunomodulatory effects of antibodies directed against TCR variable domains may account, at least in part, for the efficacy of IVIG preparations in therapy of autoimmune diseases and in the prevention of graft versus host reactions.


Assuntos
Autoanticorpos/imunologia , Idiótipos de Imunoglobulinas/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Animais , Artrite Reumatoide/imunologia , Humanos , Interleucina-2/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Linfócitos T
9.
Child Care Health Dev ; 28(1): 95-100, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11856192

RESUMO

BACKGROUND AND OBJECTIVES: In developing countries, caring for the large number of babies in orphanages is very hard work. Whereas the physical needs of most of the children are met, play often gets neglected. Studies have repeatedly shown that babies in such institutionalized settings suffer from severe psychomotor retardation. The aim of this project was to develop an intervention programme of structured play. We hypothesized that such an intervention would result in acceleration of psychosocial development in otherwise healthy institutionalized children. DESIGN: Prospective longitudinal. SETTING: Mother Teresa's Orphanage, run by Missionaries of Charity. SUBJECT AND METHODS: All 30 children in the orphanage aged 6 months-2.5 years, were assessed for their Motor, Mental and Social Quotients, using the Indian adaptation of Bailey's Scale of Infant Development(DASII) and the Vineland's Social Maturity Scale. A structured 'Regime of Play' was then built into the routine of the orphanage. A repeat developmental assessment was performed at the end of 3 months to assess the impact. RESULTS: Out of the original cohort of 30, 19 children were available for post-intervention assessments. The remainder were adopted before their assessments. Their mean Motor Quotient rose from 63.7 to 81.7, mean Mental Quotient rose from 65.8 to 89.6 and the mean Social Quotient rose from 61.9 to 91.3, a gain of 18, 23 and 30 points respectively (p < 0.0001). There was also an overall change in the environment of the orphanage. Children became more active, playful, responsive and independent. Contrary to what caretakers assumed, their workload actually decreased. The responsiveness in the children awakened as a result of play, acted as a positive feedback for caretakers to continue the play sessions. CONCLUSIONS: This study shows that short daily sessions of play can significantly improve the development of children in such institutions. It is vital to remember that children grow 'Not by Bread Alone'.


Assuntos
Desenvolvimento Infantil , Criança Institucionalizada/psicologia , Cuidados no Lar de Adoção , Ludoterapia , Pré-Escolar , Estudos de Coortes , Países em Desenvolvimento , Humanos , Índia , Lactente , Avaliação de Resultados em Cuidados de Saúde
12.
Arthritis Res ; 2(3): 205-7, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11094430

RESUMO

Human leucocyte antigen (HLA) class II molecules have been shown to be associated with predisposition to rheumatoid arthritis (RA). We generated HLA-DR and DQ transgenic mice that lacked endogenous class II molecules to study the interaction between the DR and DQ molecules and define the immunologic mechanisms in rheumatoid arthritis. Using collagen-induced arthritis (CIA) as an experimental model for inflammatory polyarthritis, we show that both DQ and DR are involved in predisposition or resistance to arthritis. Our studies suggest that polymorphism in DQB1 genes may determine predisposition to RA while the DRB1 polymorphism may dictate severity/protection of the disease. These mice provide powerful tools to develop immunotherapeutic protocols.


Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Knockout
14.
Hum Immunol ; 61(12): 1383-9, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11163096

RESUMO

On the basis of our extensive studies on collagen induced arthritis in HLA class II transgenic mice, we proposed a hypothesis to explain role of shared epitope in rheumatoid arthritis (RA) association. According to our hypothesis, complementation between both DQ and DR molecules is required for susceptibility or protection from disease. While certain DQ alleles predispose individuals to RA, DRB1 molecule can modulate disease by shaping T-cell repertoire in the thymus by providing self-peptides and presented by DQ molecules. Using A beta o.DQ8 transgenic mice, we tested ability of peptides derived from HV3 of DR molecules, implicated in RA positively or negatively, to activate T cells. While the peptides derived from RA susceptible DR molecule were poor binders and poor in activating T cells, the peptides derived from RA resistant DR molecules were high affinity binders and efficient T-cell activators. Our experiments suggest that high affinity DR peptides could induce tolerance to autoimmunity while the low affinity peptides could be permissive to autoimmunity. Using peptide from DRB1*0402 molecule, known to be associated with resistance to RA, prior to induction of collagen induced arthritis prevents the onset of disease. Thus, self-peptides derived from HLA molecules could potentially generate tolerance or autoimmunity depending on their binding affinity with HLA molecules.


Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Doenças Autoimunes/genética , Tolerância Imunológica/genética , Animais , Artrite Reumatoide/terapia , Doenças Autoimunes/terapia , Colágeno/administração & dosagem , Colágeno/imunologia , Predisposição Genética para Doença , Antígenos HLA-DQ/biossíntese , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Camundongos , Camundongos Transgênicos , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/uso terapêutico , Homologia de Sequência de Aminoácidos , Linfócitos T/imunologia
15.
Hum Immunol ; 60(9): 816-25, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10527388

RESUMO

We generated transgenic mice with DRB1*0401 gene with mutation in the beta2 domain (aa 110 and 139) for better interaction with mCD4. The DR4 transgene was introduced into H2-Aq (B10RQB3) and H2-Af (B10RFB3) to examine the role of DR4 in collagen arthritis. The HLA-DR molecules in these mice were found to be functional on the basis of their positive/negative selection of the Vbeta T cell repertoire. H2-Aq mice are resistant to porcine CII-induced arthritis. The RQB3/DR4 mice (H2Aq/DR4) developed severe collagen induced arthritis (CIA) when immunized with Porcine type II collagen while the negative littermates were resistant. RQB3.DR4 mice were also highly susceptible to CIA induced by Human CII while negative littermates got only mild disease. However, RFB3/DR4 mice (H2Af/ DR4) did not get CIA with any type II collagen. Therefore, the DR4 gene in the context of H2-Aq predisposes to severe arthritis but not in the context of H2-Af. Antibodies to renatured cyanogen bromide (CB) cleaved fragments of PII in RQB3/DR4 mice and negative littermates suggest that the presence of DR4 does not result in any differences in specificity of antibody response to CB fragments. These results indicate that a specific gene complementation occurring between DR4 and H2.Aq but not DR4 and H2Af promotes the induction of arthritis with PII and HII in these mice. A similar interaction may be involved between DR and DQ molecules in human RA.


Assuntos
Artrite Reumatoide/imunologia , Antígenos H-2/imunologia , Antígenos HLA-DR/imunologia , Antígeno HLA-DR4/imunologia , Animais , Artrite Experimental/imunologia , Artrite Reumatoide/induzido quimicamente , Colágeno/imunologia , Modelos Animais de Doenças , Resistência a Medicamentos , Expressão Gênica , Antígenos HLA-DR/biossíntese , Antígenos HLA-DR/genética , Antígeno HLA-DR4/biossíntese , Antígeno HLA-DR4/genética , Cadeias HLA-DRB1 , Humanos , Interferon gama/imunologia , Camundongos , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos T alfa-beta/biossíntese , Suínos
16.
Immunol Rev ; 169: 67-79, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10450509

RESUMO

Predisposition to develop various autoimmune disorders has been associated with certain HLA class II molecules but there is a lack of information on the pathophysiological role of HLA genes in conferring susceptibility. Various experimental animal models of autoimmune disease have been studied to address the role of immune response genes. To study the interactions involved between class II molecules (DQ and DR) and define the immunologic mechanisms in various diseases, we generated HLA-DR and DQ transgenic mice that lacked endogenous class II molecules. The HLA molecules in these mice are expressed on the cell surface and can positively select CD4+ T cells expressing various V beta T-cell receptors (TCR). A peripheral tolerance is maintained to transgenic HLA molecules thus indicating that these molecules act as self. Mouse co-stimulatory and accessory molecules can interact with the HLA-peptide-TCR complex leading to efficient T-cell activation. In this review, we describe immunogenetic models for human diseases using these transgenic mice. Our studies show that HLA class II transgene-restricted T cells recognize the immunodominant antigens and peptide epitopes, similar to HLA class II-restricted human T cells. Thus these mice provide powerful tools to understand the role of HLA class II molecules in predisposition and onset of human diseases and to develop immunotherapy and vaccines.


Assuntos
Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Genes MHC da Classe II , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Sequência de Aminoácidos , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Modelos Animais de Doenças , Humanos , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Camundongos , Camundongos Transgênicos , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Miastenia Gravis/genética , Miastenia Gravis/imunologia , Policondrite Recidivante/genética , Policondrite Recidivante/imunologia , Seleção Genética , Tireoidite Autoimune/genética , Tireoidite Autoimune/imunologia , Vacinas/genética , Vacinas/imunologia
17.
Biochim Biophys Acta ; 1433(1-2): 272-80, 1999 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-10446377

RESUMO

A non-specific acid phosphatase (APase) hydrolysing L-tyrosine-O-phosphate and 3'-AMP was purified to electrophoretic homogeneity from mature lentil seeds with apparent native molecular mass of 100 kDa and subunit molecular mass of 24 kDa. These activities appear to reside on the same protein which shows a single band in native and SDS-PAGE. The pH optimum is 5.5, while the K(m) (mM) and V(max) (micromoles/min/mg protein) for p-nitrophenyl phosphate (pNPP) are 0.7 and 9.2 and for L-tyrosine-O-phosphate 1.4 and 10.1, respectively, at 30 degrees C and for 3'-AMP, 2 and 4.4 at 37 degrees C. The protein also hydrolyses other phosphomonoesters to a lesser extent. L-Tyrosine-O-phosphate, 3'-AMP and pNPP hydrolysis is potently inhibited by micromolar orthovanadate and also to nearly the same extent by sodium fluoride, potassium tartrate and metal ions. Histidine and cysteine are likely to be involved in the catalysis. Thermal inactivation studies indicate that the active site conformations for pNPP and 3'-AMP hydrolytic activities are different. The enzyme shows the characteristics of the animal protein tyrosine phosphatase.


Assuntos
Fabaceae/enzimologia , Plantas Medicinais , Proteínas Tirosina Fosfatases/química , Monofosfato de Adenosina/metabolismo , Compostos de Anilina/metabolismo , Sítios de Ligação , Cromatografia Líquida/métodos , Cisteína/análise , Eletroforese em Gel de Poliacrilamida , Inibidores Enzimáticos/farmacologia , Histidina/análise , Cinética , Peso Molecular , Compostos Organofosforados/metabolismo , Conformação Proteica , Proteínas Tirosina Fosfatases/isolamento & purificação , Proteínas Tirosina Fosfatases/metabolismo , Sementes/enzimologia , Especificidade por Substrato
18.
Int Immunol ; 10(10): 1449-57, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9796911

RESUMO

Mouse class II-deficient HLA-DQB1*0302, DQA1*0301 (DQ8) transgenic mice are susceptible to severe collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis. To examine whether polymorphism at the DRB1 locus can modulate DQ-restricted arthritis, we generated double-transgenic (DR/DQ) mice. HLA-DRB1*1502 (DR2) and DRB1*0301 (DR3) were introduced separately into CIA susceptible DQ8.Abeta transgenic mice to generate DQ8/DR2.Abeta and DQ8/ DR3.AbetaO mice. The HLA-DR molecules in these mice were found to be functional on the basis of their positive/negative selection of the Vbeta T cell repertoire. Introduction of the DR2 gene led to a significant decrease in disease incidence in DQ8.Abeta mice, while the DR3 transgene had no effect. In vitro T cell proliferative responses against bovine Cll collagen in primed mice were higher in DQ8/DR3 mice compared with DQ8/DR2 mice. Cytokine analysis showed a Th2 profile in DQ8/DR2 mice, while DQ8/DR3 mice showed a Th1 profile. These results suggest that DRB1 polymorphism can modulate the disease.


Assuntos
Artrite/induzido quimicamente , Antígenos HLA-DQ/imunologia , Antígenos HLA-DR/genética , Animais , Artrite Reumatoide/induzido quimicamente , Colágeno/farmacologia , Modelos Animais de Doenças , Antígenos HLA-DQ/biossíntese , Antígenos HLA-DR/biossíntese , Cadeias HLA-DRB1 , Imunoglobulina G/sangue , Interleucina-4/biossíntese , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos , Camundongos Transgênicos , Peptídeos/farmacologia , Polimorfismo Genético/fisiologia , Receptores de Antígenos de Linfócitos T alfa-beta/biossíntese , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
19.
Biochem Biophys Res Commun ; 250(3): 629-34, 1998 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-9784397

RESUMO

A germination specific isozyme of acid phosphatase (EC 3.1.3.2) hydrolysing O-phospho-L-Tyrosine, pH optima 5.5 is induced in lentil seeds. When seeds at 0 h, 24 h and 36 h of germination are electrophorezed, native PAGE on specific enzyme staining shows several constitutive isozymes of acid phosphatases. At 48 h, an isozyme is induced which gradually decreases and then disappears at 108 h of germination. The short lived, induced isozyme is present in the embryo and seed-coat but not in the plumule and the radical. Induction of this isozyme is inhibited by cycloheximide and actinomycin-D and increased by plant growth regulators such as heteroauxin and gibbrellic acid treatment during germination. The induced isozyme is a single 30 kD polypeptide, with subunit molecular mass of 25 kD, shows activity for O-phospho-L-Tyrosine. It is strongly inhibited by vanadate (microM), molybdate, tungustate as also by iodoacetate, p-chloromercuribenzoate and diethylpyrocarbonate. This study shows for the first time that the germination induced low molecular weight Acid phosphatase is a Tyrosine phosphatase super family class IV enzyme, having a role in cellular differentiation and development during seed germination.


Assuntos
Fosfatase Ácida/metabolismo , Fabaceae/enzimologia , Isoenzimas/metabolismo , Plantas Medicinais , Indução Enzimática , Proteínas Tirosina Fosfatases/metabolismo , Sementes/enzimologia
20.
Proc Natl Acad Sci U S A ; 95(18): 10797-802, 1998 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-9724784

RESUMO

T helper 1 cells play a major role in protective immunity against mycobacterial pathogens. Since the antigen (Ag) specificity of CD4(+) human T cells is strongly controlled by HLA class II polymorphism, the immunogenic potential of candidate Ags needs to be defined in the context of HLA polymorphism. We have taken advantage of class II-deficient (Ab0) mice, transgenic for either HLA-DRA/B1*0301 (DR3) or HLA-DQB1*0302/DQA*0301 (DQ8) alleles. In these animals, all CD4(+) T cells are restricted by the HLA molecule. We reported previously that human DR3-restricted T cells frequently recognize heat shock protein (hsp)65 of Mycobacterium tuberculosis, and only a single hsp65 epitope, p1-20. DR3.Ab0 mice, immunized with bacillus Calmette-Guérin or hsp65, developed T cell responses to M. tuberculosis, and recognized the same hsp65 epitope, p1-20. Hsp65-immunized DQ8.Ab0 mice mounted a strong response to bacillus Calmette-Guérin but not to p1-20. Instead, we identified three new DQ8-restricted T cell epitopes in the regions 171-200, 311-340, and 411-440. DR3.Ab0 mice immunized with a second major M. tuberculosis protein, Ag85 (composed of 85A, 85B, and 85C), also developed T cell responses against only one determinant, 85B p51-70, that was identified in this study. Importantly, subsequent analysis of human T cell responses revealed that HLA-DR3+, Ag85-reactive individuals recognize exactly the same peptide epitope as DR3.Ab0 mice. Strikingly, both DR3-restricted T cell epitopes represent the best DR3-binding sequences in hsp65 and 85B, revealing a strong association between peptide-immunodominance and HLA binding affinity. Immunization of DR3.Ab0 with the immunodominant peptides p1-20 and p51-70 induced T cell reactivity to M. tuberculosis. Thus, for two different Ags, T cells from DR3.Ab0 mice and HLA-DR3+ humans recognize the same immunodominant determinants. Our data support the use of HLA-transgenic mice in identifying human T cell determinants for the design of new vaccines.


Assuntos
Proteínas de Bactérias/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Mycobacterium tuberculosis/imunologia , Sequência de Aminoácidos , Animais , Vacina BCG , Epitopos/imunologia , Humanos , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , Linfócitos T/imunologia
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