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1.
J Supercomput ; 78(17): 18777-18824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35729898

RESUMO

The Internet of Things (IoT) is increasingly becoming widespread in different areas such as healthcare, transportation, and manufacturing. IoT networks comprise many diverse entities, including smart small devices for capturing sensitive information, which may be attainable targets for malicious parties. Thus security and privacy are of utmost importance. To protect the confidentiality of data handled by IoT devices, conventional cryptographic primitives have generally been used in various IoT security solutions. While these primitives provide just an acceptable level of security, they typically neither preserve privacy nor support advanced functionalities. Also, they overly count on trusted third parties because of some limitations by design. This multidisciplinary survey paper connects the dots and explains how some advanced cryptosystems can achieve ambitious goals. We begin by describing a multi-tiered heterogeneous IoT architecture that supports the cloud, edge, fog, and blockchain technologies and assumptions and capabilities for each layer. We then elucidate advanced encryption primitives, namely wildcarded, break-glass, proxy re-encryption, and registration-based encryption schemes, as well as IoT-friendly cryptographic accumulators. Our paper illustrates how they can augment the features mentioned above while simultaneously satisfying the architectural IoT requirements. We provide comparison tables and diverse IoT-based use cases for each advanced cryptosystem as well as a guideline for selecting the best one in different scenarios and depict how they can be integrated.

2.
Mymensingh Med J ; 30(4): 1131-1138, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34605487

RESUMO

The objective of this study was to determine whether Magnetic Resonance Imaging is a sensitive and specific alternative method to clinical FIGO criteria in the staging of cervical carcinoma. This prospective cross-sectional study was conducted in the Department of Radiology and Imaging, BSMMU, Dhaka during the period of September 2018 to August 2020. A total of 60 patients were selected purposively and all are staged clinically by EUA. Then all samples underwent MRI in Department of Radiology and Imaging, BSMMU. Images of uterine cervix, corpus, vagina and parametrium were taken with a prefixed standard protocol (TIWI axial, T2WI axial and sagittal, DWI axial & DCE) and reporting was done by Radiologist. Comparison was done between the MRI and clinical FIGO criteria of staging of cervical carcinoma. P value <0.05 was considered as significant. Sensitivity & specificity of the MRI was measured. Data were analyzed by using Statistical Package for Social Sciences (SPSS) software version 23.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Out of 60 patients in this study the mean age was found 47.5±10.1 years with range from 22 to 60 years. Positive correlation (r=0.993; p=0.001) between histopathological size and MRI size of tumour. Positive correlation (r=0.950; p=0.001) between histopathological size and FIGO size of tumour. MRI findings more correlates with histopathology than clinically detected tumor size. The sensitivity, specificity, accuracy, positive and negative predictive values of MRI diagnosis evaluation for vaginal extension was 100.00%, 95.20%, 100.00%, 98.30% and 97.50% respectively. Sensitivity, specificity, accuracy, positive and negative predictive values of MRI diagnosis evaluation for parametrial invasion was 100.00%, all. In this study we observed that MRI staging was more likely to be concordant with pathological stage in comparison to the clinical stage. There was a concordance rate of 95.00% in MRI and 65.00% in clinical staging respectively. Out of 3 non-concordant cases in MRI, 2 were upstaged and 1 case was down staged in histopathology. FIGO staging concurred with histopathology in 39(65.00%) cases and differed in 21(35.00%) cases. Magnetic resonance imaging (MRI) is a sensitive and specific modality for accurate staging of cervical carcinoma in comparison with clinical FIGO criteria considering histopathology as gold standard.


Assuntos
Carcinoma , Neoplasias do Colo do Útero , Adulto , Bangladesh , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias do Colo do Útero/diagnóstico por imagem , Adulto Jovem
3.
Arch Razi Inst ; 76(2): 385-390, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34223736

RESUMO

Spiders are one of the most important orders of Arachnida comprising more than 48,000 species in the world. Except for families Uloboridae and Holarchaeidae, all others are classified as the venomous spider. However, only about 200 species are medically relevant and cause public health problems or even death. In Iran, there are 51 families and 763 species of spiders, of which the families, Theridiidae and Sicariidae are dangerous for the human being, and the first one is more prevalent. The Latrodectus is considered one of the most poisonous spiders in the world and Iran. This genus has five species in Iran, among which Latrodectus tredecimguttatus (black widow spider or &ldquo;Dolmak&rdquo;) is considered one of the most poisonous spiders in Iran. Therefore, this study aimed to investigate this species in the Northwest of Iran (West Azerbaijan, East Azerbaijan, and Ardabil provinces, Iran). Spatial distribution maps were prepared using GIS 9.4. In the current study, five adult female spiders were collected from Germi and Ardabil cities (Ardabil Province), Ahar County (East Azerbaijan province), and Urmia city (West Azerbaijan province) of Iran. These species were first observed in Ardabil province, Iran. Therefore, the presence of Latrodectus species under the rocks in wheat farms in this corner of Iran may be a threat to farms and visitors. People in these areas should wear gloves and avoid any activity that disturbs the spiders and make them aggressive.


Assuntos
Aranhas , Animais , Feminino , Irã (Geográfico)/epidemiologia , Aranhas/classificação
4.
Int J Psychol ; 55(1): 76-82, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30536800

RESUMO

Studies have shown that repressors tend to respond to self-report tools in a positive fashion which distorts the findings of studies based on questionnaires. The present study aimed to examine the way repressors respond to "Self-relevant" scales (which assess variables related to adaptive self-function) in comparison to "Health-relevant" scales (which assess physical and psychological health). Iranian university students (N = 271) responded to the Weinberger Adjustment Inventory (to differentiate between repressors and self-assured individuals), Mindful Attention and Awareness Scale, Self-control Scale, Integrative Self-knowledge Scale and Self-compassion Scale (to measure self-relevant variables), Bartone Symptoms checklist and the Depression and Anxiety Subscales of Depression, Anxiety and Stress Subscale (DASS-21) (to measure health-relevant variables). Based on responses to the Weinberger Adjustment Inventory, 101 participants fell into two groups, including repressors and self-assured individuals, and their data were further analysed. Multivariate analysis of variance showed no difference in repressors' scores in health-relevant scales compared to the self-assured group (healthy individuals), but they reported higher scores in adaptive self-relevant scales compared to the self-assured individuals. This study provides new evidence that compared to self-assured individuals, repressors differ in the way they respond to self-relevant versus health-relevant scales.


Assuntos
Autoavaliação Diagnóstica , Autorrelato , Adulto , Viés , Feminino , Humanos , Masculino , Inquéritos e Questionários , Estudos de Validação como Assunto , Adulto Jovem
7.
J Hosp Infect ; 85(2): 134-40, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23958153

RESUMO

BACKGROUND: Elizabethkingia meningoseptica is a nosocomial-adapted Gram-negative bacillus intrinsically resistant to antibiotics commonly used in the intensive care setting. An outbreak investigation commenced when five patients developed E. meningoseptica infection in two intensive care units (ICUs). METHODS: Analysis of laboratory data, case reviews, ICU workflows and extensive environmental sampling were undertaken. Molecular typing was performed using repetitive element palindromic polymerase chain reaction. Follow-up studies after interventions included environmental monitoring and a survey of staff compliance with interventions. FINDINGS: Laboratory data revealed increasing incidence of E. meningoseptica colonization or infection in ICU patients compared with preceding years. E. meningoseptica was cultured from 44% (35/79) of taps, but not from other sources. Hand hygiene sinks were used for disposal of patient secretions and rinsing re-usable patient care items. Sinks misused in this way were contaminated more often than sinks that were not misused (odds ratio 4.38, 95% confidence interval 1.68-11.39; P = 0.004). Molecular typing revealed that patient isolates had identical patterns to several isolates from hand hygiene taps. An urgent education programme was instituted to change these practices. Taps were cleaned systematically and aerators were changed. A temporary reduction in case numbers was achieved. Recolonization of taps was demonstrated on follow-up environmental screening, and cases recurred after two months. A survey revealed that 77.3% (163/213) of nursing staff still misused sinks due to time constraints or other problems adhering to the interventions. CONCLUSION: Introduction of non-sanctioned practices due to suboptimal unit design may have unintentional consequences for ICU patients. Room design and staff workflows must be optimized for patient safety as lapses in procedure can inadvertently put patients at risk.


Assuntos
Surtos de Doenças , Infecções por Flavobacteriaceae/epidemiologia , Flavobacteriaceae/isolamento & purificação , Controle de Infecções/métodos , Cuidados Críticos/métodos , Cuidados Críticos/organização & administração , Microbiologia Ambiental , Flavobacteriaceae/classificação , Flavobacteriaceae/genética , Infecções por Flavobacteriaceae/microbiologia , Genótipo , Humanos , Unidades de Terapia Intensiva , Epidemiologia Molecular , Tipagem Molecular , Quartos de Pacientes/organização & administração
8.
Oncogene ; 26(13): 1941-8, 2007 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-17001312

RESUMO

DNA-hypermethylation of SOCS genes in breast, ovarian, squamous cell and hepatocellular carcinoma has led to speculation that silencing of SOCS1 and SOCS3 genes might promote oncogenic transformation of epithelial tissues. To examine whether transcriptional silencing of SOCS genes is a common feature of human carcinoma, we have investigated regulation of SOCS genes expression by IFNgamma, IGF-1 and ionizing radiation, in a normal human mammary epithelial cell line (AG11134), two breast-cancer cell lines (MCF-7, HCC1937) and three prostate cancer cell lines. Compared to normal breast cells, we observe a high level constitutive expression of SOCS2, SOCS3, SOCS5, SOCS6, SOCS7, CIS and/or SOCS1 genes in the human cancer cells. In MCF-7 and HCC1937 breast-cancer cells, transcription of SOCS1 is dramatically up-regulated by IFNgamma and/or ionizing-radiation while SOCS3 is transiently down-regulated by IFNgamma and IGF-1, suggesting that SOCS genes are not silenced in these cells by the epigenetic mechanism of DNA-hypermethylation. We further show that the kinetics of SOCS1-mediated feedback inhibition of IFNgamma signaling is comparable to normal breast cells, indicating that the SOCS1 protein in breast-cancer cells is functional. We provide direct evidence that STAT3 pathways are constitutively activated in MCF-7 and HCC1937 cells and may drive the aberrant persistent activation of SOCS genes in breast-cancer cells. Our data therefore suggest that elevated expression of SOCS genes is a specific lesion of breast-cancer cells that may confer resistance to proinflammatory cytokines and trophic factors, by shutting down STAT1/STAT5 signaling that mediate essential functions in the mammary gland.


Assuntos
Neoplasias da Mama/genética , Citocinas/fisiologia , Regulação Neoplásica da Expressão Gênica , Substâncias de Crescimento/fisiologia , Mediadores da Inflamação/fisiologia , Proteínas Supressoras da Sinalização de Citocina/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , Transdução de Sinais , Proteína 1 Supressora da Sinalização de Citocina , Proteína 3 Supressora da Sinalização de Citocinas , Transcrição Gênica
9.
Artigo em Inglês | MEDLINE | ID: mdl-19238663

RESUMO

The borderline of Iran with Azerbaijan, Armenia and Turkey had been considered a malaria free region. However, in 1991, after the independence of the southern countries of the former Soviet Union, a new threat of malaria importation emerged from those countries into Iran, which was affected by serious epidemics of Plasmodium vivax malaria. Various factors can affect malaria resurgence in this region, such as socioeconomic conditions, especially the displacement of massive populations from war-stricken zones in the Republic of Azerbaijan. Accordingly, in some parts of West-Azerbaijan, East-Azerbaijan, Ardebile and Gilan provinces of Iran, several malaria foci were observed. Construction of dams, people traveling from neighboring countries to Iran, urbanization, irrigation projects, lack of malaria vector control, shortage of drug supplies are also major factors in malaria outbreaks in the region. An investigation was carried out on the bionomics of the main malaria vectors in the region. The result showed that Anopheles sacharovi plays an important role in malaria transmission and An. maculipennis and An. superpictus can be secondary vectors. Larvae were found in slow flowing water and channels with water plants. They were more abundant in June. The parity rate of blood-fed females was high in May. An. sacharovi is active from May to October with two peaks of activity, which occur in August and October. The population of this species is higher in animal shelters with a zoophicity of 95%. About 90% of bites took place in the second half of the night. A CDC light trap can also catch this species. Susceptibility testing using the WHO-recommended diagnostic doses of insecticides, revealed that this species is resistant to DDT and dieldrin, but susceptible to malathion, fenitrothion, propoxur, bendiocarb, lambdacyhalothrin, permethrin, cyfluthrin, etofenprox and deltamethrin.


Assuntos
Anopheles/parasitologia , Insetos Vetores/parasitologia , Malária/epidemiologia , Animais , Surtos de Doenças , Humanos , Inseticidas/uso terapêutico , Malária/prevenção & controle , Malária/transmissão , Oriente Médio/epidemiologia , Estações do Ano , Fatores Socioeconômicos , Transcaucásia/epidemiologia
10.
Eur J Radiol ; 39(2): 100-3, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11522418

RESUMO

To assess the value of accurate preoperative CT-guided needle localization of occult breast lesions, we reviewed a total of 39 needle-directed biopsies of breast tumors in 24 women. The average age was 52.9 years (range 31-67). All lesions were nonpalpable and mammographically, as well as sonographically occult. They were solely seen on MR-images. After demonstrating the suspicious region on CT scans, a hookwire was inserted. The correct position was confirmed by a control scan. The subsequent histopathological examination showed that 28 of the lesions (71.8%) were benign, among them mastopathy, fibrosis, fibroadenoma, papilloma, intramammary lymph node, liponecrosis and epitheliosis. Eleven lesions (28%) were malignant and showed either lobular, ductal or tubular cancer. Our results endorse that CT guided needle localization is a helpful method that allows a precise surgical excision of the suspect area with the removal of a minimal amount of breast tissue.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Mama/patologia , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Adulto , Idoso , Biópsia por Agulha , Feminino , Fibroadenoma/diagnóstico por imagem , Fibroadenoma/patologia , Humanos , Pessoa de Meia-Idade , Papiloma/diagnóstico por imagem , Papiloma/patologia , Cuidados Pré-Operatórios , Saúde da Mulher
11.
Clin Immunol ; 91(2): 196-205, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10227812

RESUMO

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that has been implicated in immunopathogenic mechanisms of a number of inflammatory diseases of autoimmune or infectious disease etiology. However, its exact role is still a matter of debate. In experimental mouse models, IFN-gamma has been shown to exacerbate autoimmune thyroiditis, insulin-dependent diabetes mellitus, and autoimmune neuritis while it confers protection against experimental allergic encephalomyelitis and experimental uveitis. In this study, we generated transgenic rats with constitutive expression of IFN-gamma in the eye to study its paracrine effects and to investigate whether local production of IFN-gamma also confers protection against uveitis in the rat species. We show here that chronic exposure of ocular cells to IFN-gamma results in apoptotic death of retinal ganglion cells, development of chronic choroiditis, formation of retinal in-foldings, and activation of proinflammatory genes. In contrast to its protective systemic effect in the mouse, constitutive secretion of IFN-gamma in the rat eye was found to predispose the development of severe anterior uveitis and induction of retinal degenerative processes that impair visual acuity. Our data underscore the danger in extrapolation of cytokine effects in the mouse to humans without corroborating evidence in other species.


Assuntos
Interferon gama/imunologia , Cristalino/imunologia , Degeneração Retiniana/imunologia , Uveíte Anterior/imunologia , Animais , Animais Geneticamente Modificados , Cristalinas/genética , Olho/imunologia , Olho/patologia , Feminino , Interferon gama/genética , Interferon gama/metabolismo , Cristalino/patologia , Masculino , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Uveíte Anterior/patologia
12.
J Immunol ; 162(1): 510-7, 1999 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-9886427

RESUMO

Experimental autoimmune uveitis (EAU) is a predominantly Th1-mediated intraocular inflammatory disease that serves as a model for studying the immunopathogenic mechanisms of uveitis and organ-specific autoimmune diseases. Despite the well-documented role of IFN-gamma in the activation of inflammatory cells that mediate autoimmune pathology, recent studies in IFN-gamma-deficient mice paradoxically show that IFN-gamma confers protection from EAU. Because of the implications of these findings for therapeutic use of IFN-gamma, we sought to reexamine these results in the rat, another species that shares essential immunopathologic features with human uveitis and is the commonly used animal model of uveitis. We generated transgenic rats (TR) with targeted expression of IFN-gamma in the eye and examined whether constitutive ocular expression of IFN-gamma would influence the course of EAU. We show here that the onset of rat EAU is markedly accelerated and is severely exacerbated by IFN-gamma. In both wild-type and TR rats, we found that the disease onset is preceded by induction of ICAM-1 gene expression and is characterized by selective recruitment of T cells expressing a restricted TCR repertoire in the retina. In addition, these events occur 2 days earlier in TR rats. Thus, in contrast to the protective effects of IFN-gamma in mouse EAU, our data clearly show that intraocular secretion of IFN-gamma does not confer protection against EAU in the rat and suggest that IFN-gamma may activate distinct immunomodulatory pathways in mice and rats during uveitis.


Assuntos
Doenças Autoimunes/etiologia , Interferon gama/fisiologia , Uveíte/imunologia , Animais , Animais Geneticamente Modificados , Doenças Autoimunes/patologia , Cristalinas/genética , Modelos Animais de Doenças , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/genética , Interferon gama/genética , Masculino , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Retina/imunologia , Retina/metabolismo , Subpopulações de Linfócitos T/metabolismo , Ativação Transcricional , Uveíte/etiologia , Uveíte/patologia
13.
Ann Trop Med Parasitol ; 92(2): 173-9, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9625913

RESUMO

An epidemiological survey to characterize Entamoeba histolytica/E dispar isolates from 123 human subjects was carried out in the Wonji area of Central Ethiopia, where an increased incidence of amoebic infection has been reported. In a randomized, coproparasitological study, 93 (75.6%) of the subjects were found positive for at least one species of intestinal parasite: 14 (15.1%) harboured only one species and 79 (84.9%) were infected with at least two species. In-vitro culture in Robinson's medium revealed amoebic parasites in 52 (82.5%) of the 63 cases tested. Of the 29 amoebic isolates successfully stabilized, cloned and characterized by Sargeaunt's electrophoretic technique, 27 (93.1%) were of E. dispar zymodemes (19 of zymodeme I, two each of zymodemes III, V and XI, and one each of zymodemes X and XV) and two (6.9%) were of E. histolytica (zymodeme XIII).


Assuntos
Entamebíase/epidemiologia , Adolescente , Adulto , Animais , Criança , Ensaios Enzimáticos Clínicos , Entamoeba histolytica/classificação , Entamebíase/enzimologia , Etiópia/epidemiologia , Fezes/parasitologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Ocul Immunol Inflamm ; 4(2): 105-12, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-22827415

RESUMO

Experimental autoimmune uveoretinitis (EAU) is a T cell mediated autoimmune disease that serves as a model of human intraocular inflammatory disease (uveitis). It is initiated in susceptible animals by immunization with retinal antigens, such as interphotoreceptor retinoid binding protein (IRBP) and S-Antigen (SAg) or by adoptive transfer of ocular Ag-specific uveitogenic T cells. Previous studies of T cell receptor (TCR) usage by uveitogenic T cells have implicated Vß8(+) -expressing T cells in the pathogenesis of EAU. Here, the authors have analyzed the TCR Vγ repertoire in the retinas of Lewis rats with and without EAU as well as the repertoire of several SAg- or IRBP-specific T cell lines. They detected Vγ2 transcripts in all four pathogenic lines and in the retinas of Lewis rats with EAU but not in the two non-pathogenic lines nor in the retinas of naive rats. Vγ7 transcripts were detected in RNAs obtained from the retina, regardless of whether the rat had EAU or not. However, the authors could not detect Vγ4, Vγ5 or Vγ6 TCR transcripts in any of the samples analyzed. Taken together, their data suggests a correlation between recruitment of Vγ2(+) T cells and EAU pathogenesis.

15.
Dev Biol ; 166(2): 557-68, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7813776

RESUMO

We previously generated an animal model for the study of autoimmune diseases of the eye by targeting gamma interferon (gamma IFN) expression to the lens of transgenic mice. Here, we have studied the effect of constitutive lens expression of gamma IFN on eye development of these transgenic mice. By Day 18 of embryonic development, lens and retinal differentiation programs are completely disrupted; normal lens epithelia and fibers are replaced by balloon-like cells and retinal differentiation into inner and outer neuroblastic layers is already affected. The mRNA levels of gamma E- and/or gamma F-crystallin and MIP, markers of lens cell differentiation, are drastically reduced, while expression of ICSBP, a gamma IFN-inducible transcriptional factor, is induced in the alpha ACry-gamma IFN transgenic mouse eyes. Taken together, our results suggest that constitutive expression of gamma IFN and its induction and activation of gamma IFN-inducible transcriptional factors in the eye altered the developmental fate of cells destined to become lens fiber cells by altering the pattern of lens gene expression.


Assuntos
Interferon gama/fisiologia , Cristalino/embriologia , Retina/embriologia , Animais , Sequência de Bases , Diferenciação Celular/efeitos dos fármacos , Cristalinas/genética , Primers do DNA/química , Proteínas do Olho/genética , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Interferon gama/farmacologia , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , Morfogênese/efeitos dos fármacos , RNA Mensageiro/genética
16.
Invest Ophthalmol Vis Sci ; 35(2): 332-41, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8112978

RESUMO

PURPOSE: To direct the expression of gamma IFN to the eyes of transgenic mice as a means of investigating the possible role of this lymphokine in ocular pathogenesis. METHODS: Transgenic mouse strains were generated by injection of a DNA fragment containing the murine alpha A-crystallin promoter fused to the coding sequence of murine gamma IFN gene. PCR and RT-PCR were used to screen for the presence of the transgene and mRNA analyses, respectively. Methacrylate-embedded eye sections were analyzed for morphology and cryosections for immunoperoxidase antibody staining. RESULTS: The most notable effects of gamma IFN in these transgenic mice include cataract, microphthalmia, blepharophimosis, microphakia, impairment of lens fiber formation, arrest of retinal differentiation, serous retinal detachment with presence of macrophages in the subretinal space, persistent hyperplastic primary vitreous, and corneal vascularization. MHC class II mRNA levels were significantly increased in the transgenic eyes and MHC class II proteins were expressed in their cornea, iris, ciliary body, choroid, lens and RPE. CONCLUSIONS: Ectopic expression of gamma IFN in the lens affected the growth of the whole eye, resulting in microphthalmia and microphakia. The author's data suggest that alpha ACry-gamma IFN transgenic mouse ocular cells express functional gamma IFN receptors and that interaction of gamma IFN with its receptor induced biochemical and morphologic changes in the transgenic eyes. These mice provide an animal model for the study of the linkage between aberrant MHC expression and predisposition to autoimmune diseases.


Assuntos
Oftalmopatias/imunologia , Genes MHC da Classe II , Antígenos de Histocompatibilidade Classe II/biossíntese , Interferon gama/biossíntese , Cristalino/imunologia , Animais , Sequência de Bases , Southern Blotting , Cristalinas/genética , Cristalinas/imunologia , DNA/genética , Oftalmopatias/patologia , Expressão Gênica , Técnicas Imunoenzimáticas , Interferon gama/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Dados de Sequência Molecular , Hibridização de Ácido Nucleico
17.
J Immunol ; 151(3): 1627-36, 1993 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-8393049

RESUMO

Experimental autoimmune uveoretinitis (EAU) is a T cell-mediated autoimmune disease that serves as a model of human intraocular inflammatory disease (uveitis) and is initiated in susceptible animals by immunization with retinal Ag, such as interphotoreceptor retinoid binding protein (IRBP) and S-Ag (SAg). Previous studies of TCR usage by uveitogenic T cells suggested a possible connection between pathogenicity of T lymphocytes and usage of V beta 8 family genes. Here, we have analyzed the T cell repertoire at the autoimmune site by examining V beta gene expression in the retinas of rats with SAg- or IRBP-induced uveitis. Our data show the following: 1) T cell response to SAg or IRBP is clonally heterogeneous: at least 15 of the 20 known rat TCR families were detected in the retinas of rats with EAU. 2) V beta 8+T cells were selectively increased in retina during the early stage of EAU, and the pattern of V beta 8 subfamily member utilization in the retina was Ag-dependent: V beta 8.2+ and V beta 8.3+ T cells were found in the retina of rats immunized with IRBP but only V beta 8.2+ cells in SAg-induced EAU. V beta 8.1 cells were not detected in any of the samples. 3) Kinetic change in the proportions of V beta 8.2+ and V beta 8.3+ T cells was observed in IRBP-EAU: on the day of clinical onset of disease, V beta 8.3+ cells were the only member of the V beta 8 family detected, but 24 h later, V beta 8.2+ T cells appeared and became the dominant V beta 8 clonotype in the retina. 4) The pattern of V beta 8 family member usage by T cells in uveitogenic lines specific to the corresponding Ag was similar to their utilization in the uveitic response in the retina. DNA sequence analysis of 75 V beta 8 cDNA clones from uveitogenic T cell lines revealed that, of 20 V beta 8 clones isolated from SAg-specific T cell lines, all were V beta 8.2 TCR, whereas among 55 V beta 8 clones from IRBP-specific lines, 36 were V beta 8.2 and 19 were V beta 8.3. In similarity to the retina, no V beta 8.1+ T cells were detected from these T cell lines. Taken together, our data suggest a bias towards usage of V beta 8+ cells in EAU and, depending on the autoantigen mediating the disease, particular V beta 8 subfamily member(s) were preferentially utilized or excluded from the autoimmune response.


Assuntos
Doenças Autoimunes/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Retinite/imunologia , Subpopulações de Linfócitos T/imunologia , Uveíte/imunologia , Animais , Antígenos/imunologia , Arrestina , Autoantígenos/imunologia , Sequência de Bases , Proteínas do Olho/imunologia , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Masculino , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos/química , Ratos , Ratos Endogâmicos Lew , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Retina/imunologia , Proteínas de Ligação ao Retinol/imunologia
18.
Clin Immunol Immunopathol ; 65(2): 152-60, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1382911

RESUMO

Experimental autoimmune uveoretinitis (EAU) is a T cell-mediated autoimmune disease induced in animals by immunization with retinal proteins (or synthetic fragments derived from them) in adjuvant, and it is considered a model of human autoimmune diseases of the eye. To study the T cell clonotypes that may be involved in EAU, we analyzed the T cell repertoire of three related T cell lines: the pathogenic line LR16, specific to the major uveitogenic epitope of IRBP; its pathogenic subline J; and its nonpathogenic subline A. We examined the expression of the genes coding for the variable regions of the 20 known Lewis rat T cell antigen receptor (TCR) V beta families. The nonpathogenic subline was found to contain mostly T cells expressing V beta 5, V beta 8.2, and V beta 19 while the pathogenic subline consisted mainly of cells expressing V beta 8.3 TCRs. Genomic Southern blot analysis of DNA from the pathogenic subline showed that V beta 8.3-expressing T cells were the dominant clonotype, and DNA sequence analyses of V beta 8.3 cDNAs revealed that two V beta 8.3 TCRs were expressed in the pathogenic subline. One of the V beta 8.3 cDNAs encoded a variable region gene segment identical to previously reported rat V beta 8.3 TCR while the other differed by two amino acids in the second complementarity determining region (CDR2). Taken together with previous data showing overrepresentation of V beta 8-expression in T cell lines that induce EAU, but not in nonuveitogenic T cell lines, our results suggest that V beta 8.3-expressing T cells represent a pathogenic clonotype in IRBP-induced EAU.


Assuntos
Doenças Autoimunes/imunologia , Proteínas do Olho , Receptores de Antígenos de Linfócitos T alfa-beta/biossíntese , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Linfócitos T/imunologia , Uveíte/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Southern Blotting , Linhagem Celular , DNA/análise , Olho/patologia , Expressão Gênica , Imunoterapia Adotiva , Ativação Linfocitária/imunologia , Dados de Sequência Molecular , RNA/isolamento & purificação , Ratos , Ratos Endogâmicos Lew , Proteínas de Ligação ao Retinol/genética , Proteínas de Ligação ao Retinol/imunologia , Homologia de Sequência de Aminoácidos , Transcrição Gênica , Uveíte/induzido quimicamente
19.
J Autoimmun ; 4(2): 315-24, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1652969

RESUMO

Genomic rearrangements to the T-cell receptor (TCR) V beta 8 gene locus were examined in T cells derived from the lymph nodes of Lewis rats immunized with either S-Antigen or peptides derived from interphotoreceptor retinoid binding protein (IRBP). The cells used in these studies are from T-cell lines that have been selected by several cycles of antigen/IL-2 stimulations, or clones isolated from these lines. No apparent rearrangement of the V beta 8 gene was observed by Southern analysis, suggesting that if indeed there are T cells using V beta 8 gene elements they represent small proportions of the cells in these T-cell lines that induce EAU (uveitogenic T cells) and that the lines may consist of large numbers of clones. On the other hand, we have demonstrated V beta 8 gene expression in uveitogenic T-cell populations by Northern analysis and by polymerase chain reaction (PCR). Although V beta 8 gene transcripts were detectable in pathogenic, but not in non-pathogenic, T-cell lines using a V beta 8 cDNA probe, RNA from pathogenic T cell lines did not hybridize to another probe specific for rat V beta 8.2. Taken together, these results suggest that, unlike the T-cell lines that mediate experimental allergic encephalomyelitis (EAE), some T-cell lines that induce EAU do not predominantly express V beta 8.2 gene but other member(s) of the V beta 8 family.


Assuntos
Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T Citotóxicos/imunologia , Uveíte Posterior/imunologia , Animais , Antígenos/imunologia , Antígenos/toxicidade , Arrestina , Sequência de Bases , Linhagem Celular , Proteínas do Olho/imunologia , Proteínas do Olho/toxicidade , Imunização , Imunoterapia Adotiva , Dados de Sequência Molecular , Família Multigênica , Ratos , Ratos Endogâmicos Lew/genética , Ratos Endogâmicos Lew/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta , Proteínas de Ligação ao Retinol/imunologia , Proteínas de Ligação ao Retinol/toxicidade , Linfócitos T Citotóxicos/transplante , Uveíte Posterior/etiologia , Uveíte Posterior/genética
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