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2.
Biomacromolecules ; 16(2): 564-77, 2015 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-25531946

RESUMO

Electrostatically self-assembling hybrid microparticles derived from novel cationic unsaturated arginine-based poly(ester amide) polymers (UArg-PEA) and anionic hyaluronic acid (HA) were fabricated into sub-micron-sized particles in aqueous medium with subsequent UV crosslinking treatment to stabilize the structure. These hybrid microparticles were characterized for size, charge, viscosity, chemical structure, morphology, and biological properties. Depending on the feed ratio of cationic UArg-PEA to anionic HA, the crosslinked microparticles formed spherical structures of 0.772-22.08 µm in diameter, whereas the uncrosslinked microparticles formed a core with an outer petal-like structure of 2.49-15 µm in diameter. It was discovered that the morphological structure of the self-assembled microparticles had a profound influence on their biological properties. At a 1:1 feed ratio of UArg-PEA to HA, the uncrosslinked microparticles showed no cytotoxicity toward NIH 3T3 fibroblasts at concentrations up to 20 µg/mL, and the crosslinked particles exhibited no cytotoxicity at concentrations up to 10 µg/mL. The UArg-PEA/HA hybrid microparticles exhibited a significantly lower macrophage-induced proinflammatory response (via TNF-α) than that from a pure hyaluronic acid control while retaining the beneficial anti-inflammatory IL-10 production by HA. The UArg-PEA/HA microparticles also stimulated size-dependent induction of arginase activity. Therefore, self-assembling these two types of biomaterials in a favorable nontoxic aqueous environment, having complementary biological properties like those of the currently reported UArg-PEA/HA hybrid microparticles, may provide a new class of biomaterials to improve the overall tissue microenvironment for promoting wound healing.


Assuntos
Materiais Biocompatíveis/química , Ácido Hialurônico/química , Polissacarídeos/química , Eletricidade Estática , Animais , Materiais Biocompatíveis/metabolismo , Ácido Hialurônico/metabolismo , Macrófagos/metabolismo , Camundongos , Células NIH 3T3 , Polissacarídeos/metabolismo , Propriedades de Superfície , Viscosidade
4.
Genes Immun ; 15(1): 47-53, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24285177

RESUMO

Previously we reported significant associations of the human leukocyte antigen (HLA)-DPB1 05:01 with memory against hepatitis B (HB) vaccination. However, the effects of HLA-DPB1 on antibodies to hepatitis B surface antigen (anti-HBs) kinetics were not explored. We followed up a cohort of 1974 HB booster recipients and quantified their 1-month and 1-year post-booster anti-HBs titers. A total of 681 subjects were randomly selected and typed for HLA-DPB1. We found that male subjects, undetectable pre-booster titers, and 05:01 homozygotes led to significantly lower post-booster anti-HBs titers. The geometric means (95% confidence interval (CI)) of 1-month post-booster anti-HBs titers were 4.68 (2.69-8.12), 23.01 (14.96-35.40) and 50.06 (27.20-92.13) mIU ml(-1) for subjects carrying two, one and no HLA-DPB1 05:01 allele. The corresponding figures for 1-year post-booster anti-HBs titers were 1.26 (0.73-2.18), 4.72 (3.08-7.25) and 7.32 (3.75-13.56) mIU ml(-1). There were significant associations of post-booster anti-HBs titers with the number of HLA-DPB1 risk and protective alleles. Among booster responders, anti-HBs decay rates were significantly reduced in subjects who had detectable pre-booster anti-HBs titers and the HLA-DPB1 05:01 allele. Our results indicated that HLA-DPB1 influences the kinetics of anti-HBs. The long-term memory against hepatitis B surface antigen (HBsAg) and the residual serum titers of anti-HBs after HB vaccination may be influenced by different mechanisms as evidenced by their inverse trend of associations with the 05:01 allele.


Assuntos
Cadeias beta de HLA-DP/genética , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Imunização Secundária , Adolescente , Alelos , Estudos de Coortes , Feminino , Heterozigoto , Humanos , Memória Imunológica , Lactente , Cinética , Modelos Lineares , Masculino
5.
Vox Sang ; 106(4): 316-21, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24877234

RESUMO

BACKGROUND: Source reduction is important in minimizing bacterial-contaminated risk of blood products, but previous evaluation of chlorhexidine (CHX) was confounded by inability of Tween and lecithin to neutralize CHX. The study aims to address this limitation and also evaluates the effectiveness of two CHX­alcohol-based skin disinfectants in blood donation setting. METHODS: A two-stage observational study was conducted. A single step 2% chlorhexidine gluconate/70% isopropyl alcohol brush (CHX/IPA-1) was first compared with current skin disinfection procedure consisting of sequential application of 10% povidone-iodine and 70% isopropyl alcohol (PI/IPA). Standard plates with conventional neutralizers (0·3% Tween-80, 0·1% lecithin) were used to enumerate residual bacterial counts. Then, CHX/IPA-1 was compared with another applicator CHX/IPA-2 with identical disinfectant contents using in-house plates with neutralizers (3% Tween-80, 0·3% lecithin, 0·1% histidine, 0·5% sodium thiosulphate, 3% saponin, 1% ether sulphate) having enhanced ability to neutralize CHX. RESULTS: All three products were found to reduce plate counts by > 2 log10 after disinfection. The CHX/IPA-1 group gave fewer residual bacterial growth on standard plates than PI/IPA group (5·9% vs. 61·7%, P < 0·001). With the use of in-house plates, residual bacterial growth was of no difference in both CHX/IPA-1 and CHX/IPA-2 groups (42·5% vs. 49·4%, P = 0·26). CONCLUSION: Good efficacy was observed with one-stage application of CHX/IPA in predonation skin disinfection and it could replace PI/IPA. However, the efficacy of CHX/IPA could be grossly overestimated in testing with standard plates because of insufficient neutralization


Assuntos
Álcoois/farmacologia , Doadores de Sangue , Clorexidina/análogos & derivados , Desinfetantes/farmacologia , Povidona-Iodo/farmacologia , Pele/microbiologia , Clorexidina/farmacologia , Desinfecção/métodos , Humanos
6.
Tissue Antigens ; 82(1): 77-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23581528

RESUMO

HLA-DPA1*02:02:04 is identical to DPA1*02:02:03 except for a synonymous change at nucleotide position 138 (C to G) in exon 2.


Assuntos
Alelos , Cadeias alfa de HLA-DP/genética , Sequência de Bases , Éxons/genética , Humanos , Dados de Sequência Molecular , Alinhamento de Sequência
7.
Tissue Antigens ; 82(1): 60-2, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23574607

RESUMO

The new allele, HLA-B*07:162, is identical to HLA-B*07:12 in exon 2 but has a non-synonymous substitution at position 419 (A to C) in exon 3.


Assuntos
Alelos , Povo Asiático/genética , Antígeno HLA-B7/genética , Sequência de Bases , Éxons/genética , Humanos , Dados de Sequência Molecular , Alinhamento de Sequência , Taiwan/etnologia
8.
Mult Scler ; 19(3): 299-307, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22829325

RESUMO

OBJECTIVES: Longitudinally extensive transverse myelitis (LETM) with spinal cord lesions spanning three or more vertebral segments is a key feature of neuromyelitis optica (NMO). However, the role of anti-aquaporin 4 (anti-AQP4) antibody, a sensitive biomarker of NMO, in the conversion of LETM to NMO remains uncertain. METHODS: Thirty first-ever LETM patients were retrospectively analysed and divided into two groups according to the presence of anti-AQP4 antibodies. RESULTS: Eighteen (60%) patients presented with anti-AQP4 antibodies. Fifteen (83.33%) anti-AQP4 (+) LETM patients converted to NMO, while only three of 12 (25%, p = 0.002) anti-AQP4 (-) LETM patients progressed to NMO, over a mean follow-up period of 5.63 years. Seven (38.89%) anti-AQP4 (+) and one (8.33%) anti-AQP4 (-) LETM patients received interferon-ß1a treatment, respectively. Anti-AQP4 (+) LETM patients demonstrated a higher immunogamma globulin (IgG) index (0.68 ± 0.43 versus 0.47 ± 0.19, p = 0.018), annual relapse rate (0.72 ± 0.31 versus 0.42 ± 0.17, p = 0.01) and Kurtzke Expanded Disability Status Scale (4.28 ± 2.22 versus 2.67 ± 2.26, p = 0.031), than anti-AQP4 (-) LETM patients. In spinal magnetic resonance imaging (MRIs), more than half (58.33%) of the anti-AQP4 (+) LETM patients were observed to have central grey matter-predominant involvement in the axial view, while peripheral white matter-predominant involvement (51.85%) was the most common pattern observed in the anti-AQP4 (-) LETM patients. CONCLUSION: Anti-AQP4 (+) LETM demonstrated a high conversion rate to NMO (83.33%), suggesting that anti-AQP4 (+) LETM may represent an early, isolated syndrome of NMO spectrum disorder. The greater number of patients receiving interferon-ß treatment in anti-AQP4 (+) LETM may contribute to its high annual relapse rate.


Assuntos
Aquaporina 4/imunologia , Autoanticorpos/biossíntese , Mielite Transversa/diagnóstico , Mielite Transversa/imunologia , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/imunologia , Adulto , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Mielite Transversa/patologia , Neuromielite Óptica/patologia , Estudos Retrospectivos
9.
Tissue Antigens ; 80(3): 224-30, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22731780

RESUMO

Graves disease (GD) is an autoimmune thyroid disease with a female preponderance and a wide range of ages at onset, and human leukocyte antigen (HLA) gene plays a primary role in the susceptibility to GD. We aim to investigate the associations between HLA-DRB1 alleles and Taiwanese children with GD by both case-control and family-based studies. A total of 241 unrelated children with GD, 539 healthy controls, 115 trios of affected patients and their parents, and 121 trios of unaffected siblings and their parents were recruited. HLA-DRB1 genotyping was performed by polymerase chain reaction and sequence-based typing assays. We found that DRB1*09:01 (OR=2.60, 95% CI 2.02-3.35, Pc=6.55×10(-13)) was associated with GD risk, while DRB1*12:02 (OR=0.32, 95% CI 0.20-0.53, Pc=4.55×10(-5)) was protective against GD. Transmission/disequilibrium test further confirmed an overtransmission of the DRB1*09:01 (OR 3.37, 95% CI 2.13-6.22, Pc=1.0×10(-5)) and an undertransmission of the DRB1*12:02 (OR 0.21, 95% CI 0.05-0.42, Pc=1.7×10(-3)). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA-DRB1*09:01 confers susceptibility to GD and DRB1*12:02 exerts protection against GD development in Taiwanese children.


Assuntos
Predisposição Genética para Doença , Doença de Graves/genética , Doença de Graves/imunologia , Cadeias HLA-DRB1/genética , Adolescente , Alelos , Aminoácidos/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Família , Feminino , Frequência do Gene/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Irmãos , Taiwan/etnologia , Adulto Jovem
10.
Tissue Antigens ; 80(5): 431-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23020308

RESUMO

Hashimoto disease (HD) is an autoimmune thyroid disease resulting from complex interactions between genetic and environmental factors. The human leukocyte antigen (HLA) gene has been established to be involved in the susceptibility to HD. We aim to investigate the associations between HLA-B alleles and Han Chinese children with HD by both case-control and family-based studies. A total of 108 unrelated children with HD, 380 unrelated healthy controls, 58 trios of affected patients and their parents, and 75 trios of unaffected siblings and their parents were recruited. HLA-B genotyping was performed by polymerase chain reaction and detected with a sequence-specific oligonucleotide probes system. We found that B*46:01 allele (OR = 2.31, 95% CI 1.60-3.34, P(c) = 9.99 × 10(-5)) and carrier (OR = 3.28, 95% CI 2.10-5.11, P(c) = 1.35 × 10(-6)) were associated with HD risk. Transmission/disequilibrium test further confirmed an overtransmission of the B*46:01 (OR 2.55, 95% CI 1.36-6.10, P = 6.5 × 10(-3)). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA-B*46:01 confers susceptibility to HD in Han Chinese children. Further studies with larger children cohort are required to confirm the role of B*46:01 in the development of HD.


Assuntos
Povo Asiático , Predisposição Genética para Doença , Antígenos HLA-B/genética , Doença de Hashimoto/genética , Polimorfismo Genético , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Família , Feminino , Frequência do Gene , Antígenos HLA-B/imunologia , Haplótipos , Doença de Hashimoto/imunologia , Teste de Histocompatibilidade , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Irmãos
11.
J Chem Phys ; 137(5): 054315, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22894356

RESUMO

Fluorescence excitation spectra produced through photoexcitation of N(2) using synchrotron radiation in the spectral region between 50 and 62.5 nm have been obtained with a resolution of 0.004 nm. A broadband detector (in the 115-180 nm region) was employed to monitor fluorescence originated from neutral excited atomic nitrogen fragments which are produced through direct dissociation processes and predissociation from the well-known many-electron excited Rydberg states. We have identified a new Rydberg series (2 (2)Π(g)) 4sσ, a better resolved Rydberg (D (2)Π(g)) npσ series, and also the prominent Codling series converging to the D (2)Π(g), and C (2)Σ(u)(+) states of N(2)(+), respectively. By normalizing our relative fluorescence intensities to previously measured absolute fluorescence cross-section data we obtain the cross-section data of undispersed fluorescence in the 115-180 nm region. The fluorescence quantum yields for the present photodissociative excitation processes are found to be less than 0.05. The present results may provide important data for our understanding of competitions among the various decay channels of the many-electron transition states of N(2).

12.
Int J Immunogenet ; 39(6): 524-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22536940

RESUMO

According to the IMGT/HLA Database, the DNA sequence of A*11:53 is identical to A*11:02:01 in exons 2, 3, 4 and 5 except at codon 276. A*11:53 was reported as a rare variant of A*11, while A*11:02:01 was understood to be the second most frequently observed variant of A*11 after A*11:01:01 in Taiwanese. We sequenced HLA-A locus exons 2, 3, 4 and 5 of Taiwanese blood donors (n = 50) previously typed to carry A*11:02:01. We found out all of their sequences are identical to A*11:53 in exons 2, 3, 4 and 5' part of exon 5 including codon 276.


Assuntos
Alelos , Antígeno HLA-A11/genética , Sequência de Bases , Doadores de Sangue , Bases de Dados Genéticas , Frequência do Gene/genética , Humanos , Dados de Sequência Molecular
14.
Eur J Neurol ; 18(2): 252-259, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20561038

RESUMO

BACKGROUND: Patients with acute disseminated encephalomyelitis (ADEM) may relapse and some may ultimately convert to multiple sclerosis (MS); however, no criteria that can predict MS conversion are available to date. Our aim was to describe the clinical and magnetic resonance imaging (MRI) features of patients with an initial ADEM attack and evaluate which MRI criteria can predict conversion to MS. METHODS: We retrospectively reviewed the records of 36 patients diagnosed with ADEM. We determined clinical signs/symptoms, examined the cerebrospinal fluid (CSF), and performed brain MRI scans and compared the findings between patients who did and did not convert to MS. RESULTS: Clinical signs/symptoms, and CSF analysis show no significant difference between the two groups. The rate of conversion to MS from ADEM in Taiwanese patients is low (11%) after a mean follow-up period of 28.36 months. Modified McDonald criteria were fulfilled in 19/36 patients: 21% (4/19) of those patients developed MS according to Poser criteria subsequently. Of the other patients (17/36) who did not fulfill these criteria, none converted to MS. (log rank test; P=0.027). CONCLUSIONS: It is difficult to predict from initial clinical presentations to address which patients with ADEM will convert to MS. Patients with ADEM whose brain MRI findings met the modified McDonald criteria may have clinically isolated syndrome because they have a significantly higher probability of conversion to MS. In contrast, patients whose brain MRI findings did not meeting these criteria may be considered as having classic ADEM because they have a lower probability of conversion to MS.


Assuntos
Encefalomielite Aguda Disseminada/complicações , Encefalomielite Aguda Disseminada/patologia , Esclerose Múltipla/etiologia , Esclerose Múltipla/patologia , Adulto , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan
15.
Eur J Clin Microbiol Infect Dis ; 30(2): 265-71, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20953652

RESUMO

This study investigated the correlation between antibiotic consumption and resistance among Staphylococcus aureus and enterococci causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009. Overall, the trend of total consumption (defined daily dose [DDD] per 1,000 patient-days) of glycopeptides, including vancomycin and teicoplanin, significantly increased during 2000 to 2003 and remained stable during 2004-2009. Vancomycin consumption significantly increased during 2003 and decreased after 2004. A significant decrease in the resistance rate with time was found for oxacillin- and gentamicin-resistant S. aureus. In contrast, the rates of vancomycin- and teicoplanin-resistant enterocci increased significantly. A significant correlation was found between the increased use of extended-spectrum cephalosporins, ß-lactam-ß-lactamase inhibitor combinations, carbapenems and the decreased prevalence of methicillin-resistant S. aureus (MRSA). In contrast, the increased use of teicoplanin, extended-spectrum cephalosporins, ß-lactam-ß-lactamase inhibitor combinations, and carbapenems was correlated with the increased prevalence of vancomycin-resistant enterococci (VRE). In conclusion, this 10-year study in a single institution identified different correlations between the prescription of antibiotics and the resistance rates of MRSA and VRE. Strict implementation of infection control policy based on these correlates would be helpful in decreasing the presence of these multidrug-resistant pathogens in hospitals.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Uso de Medicamentos/estatística & dados numéricos , Enterococcus/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Glicopeptídeos/uso terapêutico , Humanos , Staphylococcus aureus/isolamento & purificação , Taiwan , Teicoplanina/uso terapêutico , Vancomicina/uso terapêutico , beta-Lactamas/uso terapêutico
16.
Br J Anaesth ; 106(4): 590-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21307008

RESUMO

BACKGROUND: Lipopolysaccharide (LPS) may activate hypoxia-inducible factor (HIF)-1α, which up-regulates cytokine expression and the lethality of LPS-induced shock. We investigated the effect of propofol on HIF-1α expression and acute lung injury in LPS-treated mice. METHODS: A series of both positive and negative control experiments were performed. We injected BALB/C mice with propofol or vehicle i.p. immediately and 12 h after an LPS challenge. After 24 h, we examined the lung wet/dry weight ratio, neutrophil infiltration, and HIF-1α mRNA expression and inflammatory cytokines in the lung tissue. Survival was determined for 48 h after LPS injection. In vitro, we determined the responses of A549 cells, with and without HIF-1α silenced, to treatment with LPS alone and LPS plus propofol. RESULTS: Propofol prolonged survival and attenuated acute lung injury and decreased the expression of HIF-1α, interleukin (IL)-6, keratinocyte-derived chemokine, and tumour necrosis factor-alpha (TNF-α) in the lungs of endotoxaemic mice. In HIF-1α knockdown-A549 cells, LPS-induced TNF-α, IL-6, and the pro-apoptotic gene, BNIP3 expression and apoptosis were reduced. Propofol, but not an inhibitor of nuclear factor κB, reduced HIF-1α expression in LPS-stimulated A549 cells. Propofol also down-regulated, in A549 cells, the expression of IL-6, IL-8, and TNF-α, Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), and apoptosis. CONCLUSIONS: Propofol reduces apoptosis in LPS-stimulated lung epithelial cells by decreasing HIF-1α, BNIP3, and cytokine production. Using propofol to inhibit HIF-1α expression may protect against the acute lung injury caused by LPS-induced sepsis.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anestésicos Intravenosos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Propofol/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Anestésicos Intravenosos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Citocinas/biossíntese , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Endotoxemia/induzido quimicamente , Endotoxemia/metabolismo , Endotoxemia/prevenção & controle , Células Epiteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Lipopolissacarídeos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Propofol/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
17.
Int J Immunogenet ; 38(1): 69-71, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21040492

RESUMO

We here report sequence confirmation and analysis of the variant HLA-DRB1*14:01:03 on three voluntary bone marrow donors and the conserved haplotype carrying DRB1*14:01:03 allele in Taiwanese population. In exon 2, the DNA sequence of DRB1*14:01:03 is identical to HLA-DRB1*14:01:01 except a silent nucleotide substitution at position 192. However, sequence specific primer (SSP) reaction pattern of DRB1*14:01:03 matched with the pattern of DRB1*14:54 instead of DRB1*14:01:01, 14:01:02 or 14:01:03. In exon 3, at position 421, DRB1*14:01:03 has an identical nucleotide as DRB1*14:54 but differs from DRB1*14:01:01. We think the discrepancy of the allele assignment by SSP typing protocol and by sequence-specific oligonucleotide probe (SSO) and sequence-based typing methods should be addressed. We assume DRB1*14:54 is probably the parental allele for DRB1*14:01:03.


Assuntos
Antígenos HLA-A/genética , Cadeias HLA-DRB1/genética , Polimorfismo Genético , Povo Asiático/genética , Sequência de Bases , Haplótipos , Humanos , Dados de Sequência Molecular , Alinhamento de Sequência
18.
Int J Immunogenet ; 38(4): 277-80, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21382176

RESUMO

Using sequence-based typing method we discovered two new HLA-B*40 variants, B*40:137 and B*40:158, in Taiwanese individuals. The sequence of B*40:137 has three nucleotide (nt) changes from B*40:21 at nt 353 (C→T), nt 355 (C→A) and nt 369 (C→T) resulting two coding changes at residue 94 (T→I) and residue 95 (L→I), whereas the sequence of B*40:158 differs from B*40:01:01 with five nt substitutes at nt 463 (C→A), nt 477 (C→G), nt 499 (T→A), nt 512 (T→G) and nt 527 (T→A) causing five amino acid exchanges at codons 140 (Y→S), 155 (R→S), 168 (S→T), 171 (L→W) and 179 (V→E). Our hypotheses on the generation of the two novel alleles are presented.


Assuntos
Alelos , Povo Asiático/genética , Antígenos HLA-B/genética , Substituição de Aminoácidos/genética , Sequência de Bases , Antígeno HLA-B40 , Haplótipos , Humanos , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único/genética , Alinhamento de Sequência
19.
J Exp Med ; 175(2): 597-607, 1992 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-1732418

RESUMO

An antisense phosphorothioate (S)-oligonucleotide to a sequence in the intervening (I) region of the gamma 2b immunoglobulin (Ig) heavy chain gene inhibits Ig secretion by B cells stimulated with lipopolysaccharide (LPS) or LPS plus interleukin 4. It is also a striking stimulant of DNA synthesis by resting B cells. The antisense S-oligonucleotide causes a 10-20-fold increase in the expression of the gamma 2b germline transcript. Among mutants of the antisense S-oligonucleotide, some show all the effects whereas others are inactive. A similar hierarchy exists in the quantitative biological activities of mutant S-oligonucleotides and in their capacity to hybridize to the sense oligonucleotide, strongly suggesting that an I gamma 2b sequence in the RNA transcript or in the noncoding strand of the DNA is the target of the antisense S-oligonucleotide. The possible relationship of the overexpression of the germline gamma 2b transcript to the biological functions of the I gamma 2b antisense S-oligonucleotide is discussed.


Assuntos
Linfócitos B/imunologia , DNA/biossíntese , DNA/genética , Regulação da Expressão Gênica/imunologia , Genes de Imunoglobulinas/genética , Imunoglobulina G/biossíntese , Oligonucleotídeos Antissenso/imunologia , Animais , Sequência de Bases , Northern Blotting , Eletroforese em Gel de Poliacrilamida , Feminino , Genes de Imunoglobulinas/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , RNA Mensageiro/metabolismo , Tionucleotídeos
20.
J Exp Med ; 178(4): 1381-90, 1993 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-8376941

RESUMO

During immune responses, B lymphocytes may switch from the expression of immunoglobulin M (IgM) to the expression of another isotype (e.g., IgG, IgE, IgA). In stable hybridomas and myelomas expressing a "switched" (S) isotype, DNA deletions between S mu and a "downstream" S region (S region recombination) have been found. In primary B cells, studies of the molecular basis of switching have been limited by the ability to sensitively quantitate the amount of DNA deletion; such studies would be of interest because other nondeletional mechanisms (trans-splicing, alternative processing of a long transcript) have been proposed to account for isotype switching in certain circumstances. We have applied the digestion-circularization polymerase chain reaction (DC-PCR) technique to measure the amount of S region recombination that occurs in the course of class switching in primary B lymphocytes. Resting B cells were cultured in lipopolysaccharide (LPS) and interleukin 4 (IL-4) to stimulate switching to IgG1. These cells begin to express membrane IgG1 at day 2.5 of culture and reach maximum expression by day 4.5. DNA was prepared from cultured cells and analyzed for S mu-S gamma 1 rearrangement by DC-PCR. Chimeric switch regions, indicating S mu-S gamma 1 recombination, were detected in amounts that, in most cases, correlated with surface expression. Furthermore, when cells were sorted on the basis of surface IgG1 expression, a mean of at least one S mu-S gamma 1 rearrangement per cell was seen in five out of seven experiments. In general, the IgG1+ cells obtained at 4.5 and 5.5 d of culture had close to 2 S mu-S gamma 1 rearrangements per cell. In IgG1- cells, S mu-S gamma 1 rearrangements were detectable, but at frequencies substantially lower that in IgG1+ cells. Thus, these results indicate that DNA deletion accompanies class switching in normal B cells stimulated with LPS and IL-4.


Assuntos
Linfócitos B/imunologia , Rearranjo Gênico do Linfócito B , Imunoglobulina G/genética , Região de Troca de Imunoglobulinas/genética , Animais , Linfócitos B/efeitos dos fármacos , Sequência de Bases , Células Cultivadas , DNA , Feminino , Interleucina-4/farmacologia , Cinética , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/imunologia , Receptores Nicotínicos/genética
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