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1.
J Radiol Prot ; 44(2)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38657574

RESUMO

Nuclear energy is crucial for achieving net-zero carbon emissions. A big challenge in the nuclear sector is ensuring the safety of radiation workers and the environment, while being cost-effective. Workplace monitoring is key to protecting workers from risks of ionising radiation. Traditional monitoring involves radiological surveillance via installed radiation monitors, continuously recording measurements like radiation fields and airborne particulate radioactivity concentrations, especially where sudden radiation changes could significantly impact workers. However, this approach struggles to detect incremental changes over a long period of time in the radiological measurements of the facility. To address this limitation, we propose abstracting a nuclear facility as a complex system. We then quantify the information complexity of the facility's radiological measurements using an entropic metric. Our findings indicate that the inferences and interpretations from our abstraction have a firm basis for interpretation and can enhance current workplace monitoring systems. We suggest the implementation of a radiological complexity-based alarm system to complement existing radiation level-based systems. The abstraction synthesized here is independent of the type of nuclear facility, and hence is a general approach to workplace monitoring at a nuclear facility.


Assuntos
Exposição Ocupacional , Monitoramento de Radiação , Proteção Radiológica , Local de Trabalho , Monitoramento de Radiação/métodos , Exposição Ocupacional/análise , Humanos , Centrais Nucleares
2.
Int J Biol Macromol ; 220: 307-315, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35961561

RESUMO

The research endeavour to synthesize a novel, non-toxic, eco-friendly guar gum based biopolymeric macromolecule, [2-(methacryloyloxy) ethyl] trimethyl ammonium chloride grafted guar gum (GG-g-P (MAETMAC)) that has been optimized as a flocculant for mineral ore processing. The synthesis was performed using non-radiation and microwave assisted technique to compare and ensure the superiority of the latter. The intended grafting of monomer[2-(methacryloyloxy) ethyl] trimethyl ammonium chloride on to the biological macromolecule (guar gum) was confirmed through standard physico-chemical characterization techniques namely X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-visible) spectroscopy, intrinsic viscosity study, etc. The flocculation efficacy of the synthesized novel graft copolymer was thoroughly investigated in kaolin, coal fine, and iron ore suspensions. We have explored a graft copolymer, [2-(methacryloyloxy) ethyl] trimethyl ammonium chloride grafted guar gum that has not been studied yet to the best of our knowledge. To establish the superiority of the synthesized biomaterial, the flocculation study revealed that the best grade of the synthesized novel graft copolymer showed flocculation efficacy of 90 % in kaolin, 69 % in Iron ore, and 29 % in coal fine suspensions which was significantly higher than using alum as a coagulant which provided 36 % efficacy in kaolin, 29 % in iron ore and 10 % in coal fine suspensions.


Assuntos
Caulim , Micro-Ondas , Cloreto de Amônio , Materiais Biocompatíveis , Carvão Mineral , Floculação , Galactanos , Ferro , Caulim/química , Mananas , Gomas Vegetais , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier , Suspensões
3.
Int J Biol Macromol ; 120(Pt A): 255-262, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30134189

RESUMO

Tropical tasar silkworm Antheraea mylitta is a wild sericigenous insect which is distributed in different geographical regions and named as different ecoraces. In the present study, we investigated the molecular characterisation and cosmeceutical properties of sericin extracted from different ecoraces of tasar cocoons. The surface morphology and molecular weight of cocoons were determined by scanning electron microscope (SEM) and SDS-PAGE, respectively. Characterisation of sericin was performed by various methods such as FTIR, CHNS, TGA and amino acid analyzer. The anti-tyrosinase, anti-elastase, glutathione-S-transferase inhibition, free radical scavenging potential and inhibition of oxidative damages were measured in tasar ecoraces sericin. SEM images have revealed the removal of sericin from the surface of cocoons. SDS-PAGE of sericin depicted the presence of diverse molecular weight of proteins. Structural determination by FTIR revealed the presence of both α-helical and ß-sheet structures. Thermal properties of sericin were studied by TGA which showed a 50% weight loss at temperature 410 °C-430 °C. Additionally, ecoraces sericin contains 17 amino acids in which serine, aspartic acid and glycine are predominantly present (55.68-59.61%). Further, anti-tyrosinase, anti-elastase, inhibition of glutathione-S-transferase activity, free radical scavenging potential and inhibition of lipid peroxidation were also observed in ecoraces sericin. Our findings suggest that the present study appear to be helpful in exploiting sericin as potential biomaterial in cosmeceutical and allied field.


Assuntos
Cosméticos/química , Sequestradores de Radicais Livres/química , Mariposas/química , Sericinas/química , Animais , Temperatura Alta , Estrutura Secundária de Proteína
4.
Int J Biol Macromol ; 114: 1102-1108, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29550421

RESUMO

The present study investigates the properties of sericin extracted from tasar silk fiber waste (TSFW). The surface morphology of TSFW was observed by scanning electron microscope (SEM). SEM images revealed the removal of residual sericin over the surface of TSFW. The molecular weight distribution of sericin was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results suggested that TSFW sericin represented a family of proteins with wide-ranging molecular weight distribution (11-245 kDa). Structural determination by FTIR revealed the presence of both α-helical and ß-sheet structures. The colour was studied by colorimeter indicating less brightness, more red and yellow colour intensities. The carbon: nitrogen ratio (C:N) was studied by CHNS element analyzer and the ratio is 5.15-7.85. Thermal properties of TSFW sericin have been studied by thermogravimetric analysis (TGA) method. TGA curve showed higher thermal stability and variable degradation profiles. Furthermore, TSFW sericin contains 17 amino acids where serine, aspartic acid and glycine are the more significant compounds (54.34-60.49%). In addition, sericin was found to inhibit tyrosinase, elastase and glutathione-S-transferase activity, and had apparent radical scavenging impacts on 2.2­diphenyl­1­picryl­hydrazil (DPPH), hydrogen peroxide and inhibition of lipid peroxidation. Result suggested that TSFW sericins might be a valuable ingredient for cosmoceutical products.


Assuntos
Antioxidantes/química , Inibidores Enzimáticos/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Elastase Pancreática/antagonistas & inibidores , Sericinas/química , Monofenol Mono-Oxigenase/química , Elastase Pancreática/química
5.
J Environ Biol ; 37(4): 543-50, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27498499

RESUMO

The present study provides information about the concentrations of Vitamin B (thiamine, riboflavin, pyridoxine and niacin) in polished brown rice treated with xylanase. Xylanase enzyme was produced from Aspergillus awamori MTCC 9166. Brown rice was treated with 60-100% enzyme (40 ml of buffer -undiluted) for 30 to 150 min (with variation of 30 min) at 30 degrees C to 50 degrees C (with variation of 5 degrees C) to attain a saturated moisture level of 35.5 g100(-1)g .The enzyme acted upon selective degradation (polishing time 10-50 sec) of bran layer facilitating retention of more vital nutrients along with the vitamins. Vitamin B content, detected through HPLC and optimized by response surface methodology (RSM) with central composite design (CCRD), demonstrated that selective degradation of bran layers for polished rice facilitated increase of thiamine (57%), riboflavin (48%), pyridoxine (90%) and niacin (55%) concentration in bio polished rice over normally milled rice.Enzyme treated bio-polished rice was considered to be better source of vitamin B complex than mechanically milled rice, hence more nutritionally efficacious.


Assuntos
Oryza/química , Complexo Vitamínico B/análise , Xilosidases/análise , Grão Comestível/química
6.
Clin Exp Immunol ; 182(3): 289-301, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26332605

RESUMO

VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 µg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 µg/ml for the same two doses. Over the 5-40 mg/kg i.v. dose range (n = 18), the clearance was 0.016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.


Assuntos
Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Anti-HIV , Infecções por HIV , HIV-1 , Adolescente , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Amplamente Neutralizantes , Relação Dose-Resposta a Droga , Feminino , Anticorpos Anti-HIV/administração & dosagem , Anticorpos Anti-HIV/efeitos adversos , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade
7.
Clin Exp Immunol ; 178(1): 75-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24852823

RESUMO

Cyclin B1 is a checkpoint protein that regulates cell division from G2 to the M phase. Studies in mice have shown that cyclin B1 vaccine-induced immunity significantly delayed or prevented the spontaneous cancer development later in life. We hypothesized that if these results showing a protective effect of anti-cyclin B1 antibodies could be extrapolated to the human condition, cancer-free individuals should have higher levels of endogenous antibodies than patients with cancers characterized by the over-expression of this tumour-associated antigen. To test this hypothesis, we characterized a large (1739 subjects) number of multi-ethnic patients with breast cancer (which over-expresses cyclin B1) and matched controls for anti-cyclin B1 immunoglobulin (Ig)G antibodies. Multivariate analyses, after adjusting for the covariates, showed that cancer-free individuals had significantly higher levels of naturally occurring IgG antibodies to cyclin B1 than patients with breast cancer (mean ± standard deviation: 148·0 ± 73·6 versus 126·1 ± 67·8 arbitrary units per ml; P < 0·0001). These findings may have important implications for cyclin B1-based immunotherapy against breast cancer and many other cyclin B1-over-expressing malignancies.


Assuntos
Anticorpos/imunologia , Antígenos de Neoplasias/imunologia , Neoplasias da Mama/imunologia , Ciclina B1/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia
8.
Clin Exp Immunol ; 176(1): 78-83, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24304136

RESUMO

GM (γ marker) allotypes, genetic variants of immunoglobulin γ chains, have been reported to be associated strongly with susceptibility to lung cancer, but the mechanism(s) underlying this association is not known. One mechanism could involve their contribution to humoral immunity to lung tumour-associated antigens. In this study, we aimed to determine whether particular GM and KM (κ marker) allotypes were associated with antibody responsiveness to XAGE-1b, a highly immunogenic lung tumour-associated cancer-testis antigen. Sera from 89 patients with non-small cell lung cancer (NSCLC) were allotyped for eight GM and two KM determinants and characterized for antibodies to a synthetic XAGE-1b protein. The distribution of various GM phenotypes was significantly different between XAGE-1b antibody-positive and -negative patients (P = 0·023), as well as in the subgroup of XAGE-1b antigen-positive advanced NSCLC (P = 0·007). None of the patients with the GM 1,17 21 phenotype was positive for the XAGE-1b antibody. In patients with antigen-positive advanced disease, the prevalence of GM 1,2,17 21 was significantly higher in the antibody-positive group than in those who lacked the XAGE-1b antibody (P = 0·026). This phenotype also interacted with a particular KM phenotype: subjects with GM 1,2,17 21 and KM 3,3 phenotypes were almost four times (odds ratio = 3·8) as likely to be positive for the XAGE-1b antibody as the subjects who lacked these phenotypes. This is the first report presenting evidence for the involvement of immunoglobulin allotypes in immunity to a cancer-testis antigen, which has important implications for XAGE-1b-based immunotherapeutic interventions in lung adenocarcinoma.


Assuntos
Antígenos de Neoplasias/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Imunidade Humoral/imunologia , Cadeias gama de Imunoglobulina/imunologia , Cadeias kappa de Imunoglobulina/imunologia , Neoplasias Pulmonares/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Frequência do Gene , Haplótipos , Humanos , Imunidade Humoral/genética , Alótipos Gm de Imunoglobulina/genética , Alótipos Gm de Imunoglobulina/imunologia , Cadeias gama de Imunoglobulina/genética , Cadeias kappa de Imunoglobulina/genética , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Testículo/imunologia , Testículo/metabolismo
9.
Lett Appl Microbiol ; 57(1): 63-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23574004

RESUMO

UNLABELLED: Organophosphate hydrolase (OPH), the product of an organophosphate-degrading (opd) gene cloned from Brevundimonas diminuta, hydrolyses the triester linkage found in neurotoxic organophosphate (OP) insecticides and nerve agents. Despite the fact that OPHs have a broad substrate range, OP compounds with a P-S linkage, such as insecticides like acephate, are poor substrates for the enzyme. Expression of OPH in acephate-utilizing Pseudomonas sp. Ind01 generated a live biocatalyst capable of degrading a wide range of OP insecticides. The heterologously expressed OPH, which is a substrate of twin arginine transport (Tat) pathway, successfully targeted to the membrane of Pseudomonas sp. Ind01. The membrane-associated OPH had a size that coincided with the mature form of OPH (mOPH), suggesting successful processing and targeting of the expressed OPH to the membrane. Pseudomonas sp. Ind01 expressing OPH degraded a variety of OP insecticides besides using acephate as sole carbon source. SIGNIFICANCE AND IMPACT OF THE STUDY: A biocatalyst capable of degrading a wide range of organophosphate (OP) insecticides was generated by expressing an organophosphate degradation gene in Pseudomonas sp. Ind01 involved in mineralization of acephate. The biocatalyst can be used to eliminate a wide range of OP insecticide residues from the environment.


Assuntos
Inseticidas/metabolismo , Compostos Organofosforados/metabolismo , Monoéster Fosfórico Hidrolases/genética , Pseudomonas/metabolismo , Biodegradação Ambiental , Caulobacteraceae/enzimologia , Caulobacteraceae/genética , Hidrólise , Compostos Organotiofosforados/metabolismo , Resíduos de Praguicidas , Fosforamidas/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Pseudomonas/classificação , Pseudomonas/enzimologia , Pseudomonas/genética
10.
Clin Exp Immunol ; 171(3): 273-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23379433

RESUMO

Tumour-associated antigen human epidermal growth factor receptor 2 (HER2) is over-expressed in 25-30% of breast cancer patients and is associated with poor prognosis. Naturally occurring anti-HER2 antibody responses have been described in patients with HER2 over-expressing tumours. There is significant interindividual variability in antibody responsiveness, but the host genetic factors responsible for this variability are poorly understood. The aim of the present investigation was to determine whether immunoglobulin genetic markers [GM (genetic determinants of γ chains)] and Fcγ receptor (FcγR) alleles contribute to the magnitude of natural antibody responsiveness to HER2 in patients with breast cancer. A total of 855 breast cancer patients from Japan and Brazil were genotyped for several GM and FcγR alleles. They were also characterized for immunoglobulin (Ig)G antibodies to HER2. In white subjects (n = 263), GM 23-carriers had higher levels of anti-HER2 antibodies than non-carriers of this allele (p = 0·004). At the GM 5/21 locus, the homozygotes for the GM 5 allele had higher levels of anti-HER2 antibodies than the other two genotypes (P = 0·0067). In black subjects (n = 42), FcγRIIa-histidine/histidine homozygotes and FcγRIIIa-phenylalanine/valine heterozygotes were associated with high antibody responses (P = 0·0071 and 0·0275, respectively). FcγR genotypes in white subjects and GM genotypes in black subjects were not associated with anti-HER2 antibody responses. No significant associations were found in other study groups. These racially restricted contributions of GM and FcγR genotypes to humoral immunity to HER2 have potential implications for immunotherapy of breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Imunidade Humoral/genética , Alótipos Gm de Imunoglobulina/genética , Grupos Raciais/genética , Receptor ErbB-2/imunologia , Receptores de IgG/genética , Alelos , Povo Asiático/genética , População Negra/genética , Brasil , Neoplasias da Mama/terapia , Feminino , Genótipo , Humanos , Imunoterapia , Japão , População Branca/genética
11.
Clin Exp Immunol ; 166(3): 361-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22059994

RESUMO

Antibody-dependent cell-mediated cytotoxicity (ADCC), which links the innate and the adaptive arms of immunity, is a major host immunosurveillance mechanism against tumours, as well as the leading mechanism underlying the clinical efficacy of therapeutic antibodies such as cetuximab and trastuzumab, which target tumour antigens, human epidermal growth factor receptor (HER)1 and HER2, respectively. Immunoglobulin (Ig)G antibody-mediated ADCC is triggered upon ligation of Fcγ receptor (FcγR) to the Fc region of IgG molecules. It follows that genetic variation in FcγR and Fc could contribute to the differences in the magnitude of ADCC. Genetic variation in FcγR is known to contribute to the differences in the magnitude of ADCC, but the contribution of natural genetic variation in Fc, GM allotypes, in this interaction has hitherto not been investigated. Using an ADCC inhibition assay, we show that IgG1 expressing the GM 3+, 1-, 2- allotypes was equally effective in inhibiting cetuximab- and trastuzumab-mediated ADCC of respective target cells, in the presence of natural killer (NK) cells expressing either valine or phenylalanine allele of FcγRIIIa. In contrast, IgG1 expressing the allelic GM 17+, 1+, 2+ allotypes was significantly more effective in inhibiting the ADCC - mediated by both monoclonal antibodies - when NK cells expressed the valine, rather than the phenylalanine, allele of FcγRIIIa. These findings have important implications for engineering antibodies (with human γ1 constant region) against malignancies characterized by the over-expression of tumour antigens HER1 and HER2 - especially for patients who, because of their FcγRIIIa genotype, are unlikely to benefit from the currently available therapeutics.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais/farmacologia , Citotoxicidade Celular Dependente de Anticorpos , Alótipos Gm de Imunoglobulina/genética , Células Matadoras Naturais/imunologia , Anticorpos Monoclonais/imunologia , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Linhagem Celular Tumoral , Cetuximab , Genótipo , Humanos , Alótipos de Imunoglobulina , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Alótipos Gm de Imunoglobulina/biossíntese , Células Matadoras Naturais/metabolismo , Neoplasias , Receptores de IgG/química , Receptores de IgG/genética , Trastuzumab
12.
Orthod Craniofac Res ; 12(2): 129-40, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19419456

RESUMO

OBJECTIVES: To investigate genetic, biologic, and mechanical factors that affect speed of human tooth movement. Setting and Sample Population - Sixty-six maxillary canines in 33 subjects were translated distally for 84 days. MATERIAL AND METHODS: Distal compressive stresses of 4, 13, 26, 52, or 78 kPa were applied to maxillary canines via segmental mechanics. Dental casts and gingival crevicular fluid (GCF) samples were collected nine to 10 times/subject over 84 days at 1- to 14-day intervals. Three-dimensional tooth movements were measured using a microscope and each subject's series of dental casts. GCF samples were analyzed for total protein, interleukin-1beta (IL-1beta), and interleukin-1 receptor antagonist (IL-1RA). Cheek-wipe samples from 18 subjects were typed for IL-1 gene cluster polymorphisms. RESULTS: Average speeds of distal translation were 0.028 +/- 0.012, 0.043 +/- 0.019, 0.057 +/- 0.024, 0.062 +/- 0.015, and 0.067 +/- 0.024 mm/day for 4, 13, 26, 52, and 78 kPa, respectively. Most teeth moved showed no lag phase (63/66). Three factors significantly affected speed (p = 0.0391) and provided the best predictive model (R(2) = 0.691): Activity index [AI = experimental (IL-1beta/IL-1RA)/control (IL-1beta/IL-1RA)], IL-1RA in GCF, and genotype at IL-1B. CONCLUSIONS: Increased AI and decreased IL-1RA in GCF plus having > or =1 copy of allele 2 at IL-1B(+3954) were associated with faster tooth movement in humans.


Assuntos
Líquido do Sulco Gengival/imunologia , Interleucina-1/genética , Polimorfismo Genético/genética , Técnicas de Movimentação Dentária , Adolescente , Adulto , Alelos , Pareamento de Bases/genética , Criança , Dente Canino/patologia , Feminino , Genótipo , Líquido do Sulco Gengival/metabolismo , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Proteína Antagonista do Receptor de Interleucina 1/análise , Interleucina-1alfa/análise , Interleucina-1beta/análise , Masculino , Repetições Minissatélites/genética , Proteínas/análise , Rotação , Estresse Mecânico , Fatores de Tempo , Coroa do Dente/patologia , Torque , Adulto Jovem
13.
Tissue Antigens ; 73(4): 353-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19317746

RESUMO

To examine the role of genetic factors in development of immune thrombocytopenic purpura (ITP) in association with Helicobacter pylori infection, gene polymorphisms within the loci for human leukocyte antigen class II, interleukin (IL)-1beta (-511), tumor necrosis factor-beta (+252), immunoglobulin (Ig)G1 heavy chain (+643), and Igkappa light chain (+573) were determined in 164 adults with ITP and 75 healthy controls. Of these gene polymorphisms, the IL-1beta (-511) T allele was less frequently detected in H. pylori-infected than in H. pylori-uninfected (58% vs 81%, P = 0.01, odds ratio = 0.31) ITP patients diagnosed before age 50. These findings suggest that a single nucleotide polymorphism within the IL-1beta (-511) may affect susceptibility to early-onset ITP associated with H. pylori infection.


Assuntos
Infecções por Helicobacter/genética , Helicobacter pylori/patogenicidade , Interleucina-1beta/genética , Polimorfismo de Nucleotídeo Único , Púrpura Trombocitopênica Idiopática/genética , Adolescente , Adulto , Feminino , Predisposição Genética para Doença , Infecções por Helicobacter/etiologia , Humanos , Interleucina-1beta/imunologia , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/imunologia , Adulto Jovem
14.
Sarcoidosis Vasc Diffuse Lung Dis ; 25(2): 125-32, 2008 12.
Artigo em Inglês | MEDLINE | ID: mdl-19382531

RESUMO

Sarcoidosis is a systemic granulomatosis of unknown etiology despite being described over 100 years ago. While both genetic predisposition and environmental exposures have been proposed as playing a role in this disease, there have not been any systematic investigations of gene-environmental interaction in this disease. In the ACCESS dataset, detailed environmental histories and high resolution HLA class II typing were performed on 476 cases of newly diagnosed sarcoidosis and 476 matched controls from the patients' community. We evaluated gene-environmental interactions in exposures or HLA class II alleles that were present in > 5% of the population and had an odd ratio of > 1.0. Four exposures and four HLA Class II alleles met these criteria and were evaluated. Significant interaction was observed between HLA DRB1*1101 and insecticide exposure at work (p < 0.10) and suggestive interaction was observed between HLA DRB1*1101 and exposure to mold and musty odors and DRB1*1501 and insecticide exposure at work (P < 0.15). In addition, HLA DRB1*1101 and insecticide exposure at work was associated with extrapulmonary sarcoidosis, specifically cardiac sarcoidosis and hypercalcemia (p<0.05) and HLA DRB1*1101 and exposure to molds and musty odors was associated with pulmonary only sarcoidosis (P < 0.05). These studies suggest that sarcoidosis is due to an interaction of genetic predisposition and environmental exposure in at least some cases of sarcoidosis. Future studies in defined phenotypes of sarcoidosis may be necessary to define environmental and genetic associations with sarcoidosis.


Assuntos
Autoimunidade/genética , DNA/genética , Exposição Ambiental , Genes MHC da Classe II/genética , Predisposição Genética para Doença , Sarcoidose/genética , Adulto , Alelos , Feminino , Seguimentos , Genes MHC da Classe II/imunologia , Humanos , Masculino , Estudos Prospectivos , Sarcoidose/imunologia , Sarcoidose/patologia
15.
Clin Exp Immunol ; 150(3): 518-22, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17924968

RESUMO

Particular alleles of human leucocyte antigen (HLA) and immunoglobulin gamma (GM) and immunoglobulin kappa (KM) allotypes (polymorphic determinants of IgG heavy chains and kappa-type light chains, respectively) are associated with the outcome of several infections. To examine their role in the outcome of hepatitis C virus (HCV) infection, we genotyped 50 individuals with resolved and 117 with persistent HCV infection. None of the GM, KM or HLA-C genotypes by themselves were associated with the resolution or persistence of HCV infection. However, particular combinations of HLA and GM genotypes were associated significantly with the outcome of HCV infection. Subjects with the HLA C1C1 genotype, in the absence of GM ff, were more than seven times [odds ratio (OR) 7.15] as likely to have persistent infection as the subjects who lacked both these genotypes. The presence of GM ff, in the absence of HLA C1C2, was associated with the resolution of infection (OR 0.27). The absence of GM fz, in the presence of HLA C2C2, was also associated with the resolution of infection (OR 0.27). Compared to the subjects who lacked both these genotypes, subjects with GM fz, in the absence of HLA C1C2, were almost four times as likely to have persistent infection (OR 3.91); similarly, subjects with HLA C1C2, in the absence of GM fz, were almost three times as likely to have persistent infection (OR 2.80). These results show, for the first time, interactive effects of GM and HLA genotypes in the outcome of HCV infection.


Assuntos
Antígenos HLA-C/genética , Hepatite C Crônica/genética , Alótipos Gm de Imunoglobulina/genética , Epistasia Genética , Feminino , Genes de Imunoglobulinas , Predisposição Genética para Doença , Genótipo , Hepatite C Crônica/imunologia , Teste de Histocompatibilidade , Humanos , Alótipos Km de Imunoglobulina/genética , Masculino
16.
Parasite Immunol ; 29(5): 267-9, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17430550

RESUMO

Fulani and Masaleit, sympatric tribes in eastern Sudan, are characterized by marked differences in susceptibility to Plasmodium falciparum malaria. To determine whether the two tribes differ in the frequency of immunoglobulin GM/KM allotypes, which are associated with immunity to several pathogens, serum samples from 50 Fulani and 50 age- and sex-matched Masaleit subjects were allotyped for several GM/KM determinants. The distribution of GM phenotypes as a whole, as well as a particular combination of KM and GM phenotypes, differed significantly between the two tribes (P = 0.03). These data suggest that GM allotypes may contribute to the genetic aetiology of malaria.


Assuntos
Alótipos Gm de Imunoglobulina/sangue , Alótipos Km de Imunoglobulina/sangue , Malária/imunologia , Suscetibilidade a Doenças , Humanos , Alótipos Gm de Imunoglobulina/genética , Alótipos Km de Imunoglobulina/genética , Desequilíbrio de Ligação , Fenótipo
17.
Rheumatol Int ; 27(3): 219-24, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16944158

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex deposition. We genotyped immunoglobulin allotypes of G1M (f,z), G2M (n+,n-), G3M (b,g) and KM (1,3) in 142 Korean patients with SLE and 200 healthy controls to investigate the role of the allotypes in SLE. The allele frequency of G1M (z) was significantly higher in patients with SLE as compared to the healthy controls (94.6% vs. 84.3%, corrected P = 0.0004, OR 3.30, 95% CI 1.71-6.88). The frequency of G2M (n-) allele was also higher in patients with SLE (95.3% vs. 88.3%, corrected P = 0.008, OR = 2.71, 95% CI 1.38-5.72). Distribution of the tested allele frequencies for G3M and KM were not different between the patients and controls. In the respect of antibody production, there was increased genotype frequency of G1M (z/z) in anti-Sm(-) SLE (P = 0.023 vs. control, P = 0.042 vs. anti-Sm (+) SLE). In conclusion, particular genotypes at G1M (f,z) and G2M (n+,n-) loci are significantly associated with SLE. These immunoglobulin genes may contribute to the etiology of SLE and production of autoantibodies.


Assuntos
Alótipos Gm de Imunoglobulina/genética , Alótipos Km de Imunoglobulina/genética , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Coreia (Geográfico) , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Pessoa de Meia-Idade
18.
Clin Exp Rheumatol ; 24(2): 176-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16762154

RESUMO

OBJECTIVE: To determine whether elevated levels of antibodies to HCMV protein UL83 were present in patients with SSc and if their prevalence was associated with major SSc-associated autoantibodies. METHODS: The study population consisted of 253 Caucasian subjects (110 SSc patients and 143 controls). IgG antibodies to UL83 were measured by an enzyme-linked immunosorbent assay (ELISA). Antibodies to centromere and RNA polymerase (RNAP) were determined by indirect immunofluorescence and immnoprecipitation methods, respectively. RESULTS: The mean level of anti-UL83 antibodies in the sera of SSc patients as a whole was significantly higher than that in control subjects (14.75 vs 10.6 units/microl, p = 0.002). Both subgroups of patients contributed to this variation: compared to controls, anti-UL83 antibody levels were higher in diffuse (16.32 vs 10.6 units/microl, p = 0.012) as well as in those with the limited form of the disease (13.95 vs 10.6 units/microl, p = 0.015). Anti-UL83 antibodies were not associated with major SSc associated autoantibodies. CONCLUSION: Humoral immunity to HCMV protein UL83 may be relevant to the etiopathogenesis of scleroderma.


Assuntos
Autoanticorpos/sangue , Infecções por Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Imunoglobulina G/sangue , Fosfoproteínas/imunologia , Escleroderma Sistêmico/imunologia , Proteínas da Matriz Viral/imunologia , Centrômero/imunologia , Citomegalovirus/imunologia , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/complicações , DNA Topoisomerases Tipo I/imunologia , RNA Polimerases Dirigidas por DNA/imunologia , Humanos , Escleroderma Sistêmico/virologia
19.
Genes Immun ; 6(3): 274-8, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15772682

RESUMO

Systemic sclerosis (SSc; scleroderma) is a connective tissue disease, characterized by fibrotic, immunological, and vascular abnormalities. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that modulates collagen production and B-cell survival. To determine if certain IL-10 genotypes are risk factors for the development of SSc and influence disease-associated autoimmune responses, 248 Caucasian and 264 Japanese SSc patients and controls were genotyped for three loci: -3575, -2849, and -2763. Sera from patients were characterized for SSc-associated autoantibodies. In Caucasians, at -3575 and -2763, the frequency of AA homozygotes was higher in patients as compared with controls (P=0.0005; P=0.002). In Japanese subjects, the frequency of AC heterozygotes at -2763 was higher, and that of CC homozygotes lower, in patients with diffuse SSc as compared to controls (P=0.04). Particular IL-10 genotypes were associated with SSc-related autoantibodies. These results suggest that IL-10 genotypes contribute to the etiology of scleroderma.


Assuntos
Autoimunidade/genética , Interleucina-10/genética , Escleroderma Sistêmico/genética , Autoimunidade/imunologia , Distribuição de Qui-Quadrado , Genótipo , Heterozigoto , Homozigoto , Humanos , Japão , Escleroderma Sistêmico/imunologia , População Branca
20.
Fish Physiol Biochem ; 31(2-3): 271-4, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20035469

RESUMO

Effect of experimentally induced thyroxine overdose on the testis and seminal vesicles was studied in the air-breathing catfish, Clarias gariepinus during the preparatory and the pre-spawning phase. The present study revealed a marked reduction in testosterone level in serum, testis and seminal vesicles (SV). Histological examination showed a considerable reduction in the number of spermatozoa/spermatids in the seminiferous tubular lumen as well as depletion of fluid in the loculi of SV. SDS-PAGE analysis of SV fluid proteins demonstrated a significant decrease in the level of a ~27 kDa protein in thyroxine treated fishes. Evidences are presented here to indicate that thyroid hormone plays a role in regulating testis and SV function in catfish.

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