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OBJECTIVE: This experiment evaluated the effect of dietary supplementation levels of rapeseed meal (RSM) in gestation diets on reproductive performance, blood profiles, milk composition of sows, and growth of their progeny. METHODS: A total of 55 mixed-parity sows (Yorkshire×Landrace; average parity = 3.82) with an initial body weight (BW) of 193.0 kg were used in this experiment. Sows were allotted to one of 5 treatments at breeding based on BW and backfat thickness in a completely randomized design. Treatments consisted of dietary RSM supplementation levels (0%, 3%, 6%, 9%, and 12%) in gestation diets. During lactation all sows were fed a common lactation diet with no RSM supplementation. RESULTS: Body weight, backfat thickness, litter size, lactation feed intake, and milk composition of sows, and growth of their progeny were not different among dietary treatments. In blood profiles, a quadratic increase (Quadratic, p<0.05) in serum triiodothyronine (T3) concentration and a linear increase (Linear, p<0.01) in serum thyroxine (T4) concentration were observed at d 110 of gestation as dietary RSM supplementation levels increased. However, serum T3 and T4 concentrations in lactating sows and their piglets were not affected by RSM supplementation of gestation diets. Concentrations of serum total cholesterol and low density lipoprotein cholesterol in sows were not influenced by dietary treatments, whereas serum glucose level in sows decreased linearly at d 110 of gestation (Linear, p<0.05) by increasing dietary RSM supplementation in gestation diets. CONCLUSION: The RSM could be supplemented to gestation diets up to 12% with no detrimental effects on reproductive performance and growth of their progeny. However, increasing supplementation levels of RSM in gestation diets may increase serum T3 and T4 concentrations and decrease serum glucose concentration of sows in late gestation.
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This study was conducted to investigate the influence of dietary rapeseed meal (RSM) on growth performance, blood profiles, nutrient digestibility and economic benefit of growing-finishing pigs. A total of 120 growing pigs ([Yorkshire×Landrace] ×Duroc) with an initial body weight (BW) 29.94±0.06 kg were used in this experiment. Pigs were randomly allotted into 1 of 5 treatments in a randomized complete block design and 6 replicates with 4 pigs per pen. Treatments were divided by dietary RSM supplementation levels (0%, 3%, 6%, 9%, or 12%) in growing-finishing diets. A linear decrease (p<0.05) of BW and average daily gain (ADG) were observed at 13th wk of finishing and overall periods of pigs. Additionally, gain-to-feed ratio (G/F) tended to decrease by dietary RSM supplementation in growing-finishing diets (linear, p = 0.07 and quadratic, p = 0.08). Concentrations of serum triiodothyronine and thyroxine were not influenced by dietary RSM treatments whereas thyroid gland and liver weight were increased at 13th wk of finishing period (linear, p<0.05; p<0.01) by increasing dietary RSM supplementation level. In blood profiles, serum total cholesterol and low density lipoprotein cholesterol concentrations were not differed by dietary treatments at 13th wk of finishing period whereas concentration of serum high density lipoprotein cholesterol was affected by the supplementation level of RSM, resulting in a linear RSM level responses (p<0.05). Serum blood urea nitrogen concentration tended to decrease (linear, p = 0.07; p = 0.08) at 6th wk of growing and 13th wk of finishing periods and digestibility of dry matter tended to decrease by dietary RSM (linear, p = 0.09). Crude protein, crude fat and nitrogen retention, whereas, were not affected by dietary RSM supplementation level. In the economic analysis, feed cost per weight gain was numerically decreased when RSM was provided up to 9%. Consequently, RSM could be supplemented to growing-finishing diets up to 9% (3.07 µmol/g Gls) without detrimental effects on growth performance of growing-finishing pigs.
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The role of major histocompatibility complex (MHC) class I chain-related gene A (MICA), a ligand of NKG2D, has been defined in human diseases by its allele associations with various autoimmune diseases, hematopoietic stem cell transplantation (HSCT) and cancer. This study describes a practical system to develop MICA genotyping by allele-specific primer extension (ASPE) on microarrays. From the results of 20 control primers, strict and reliable cut-off values of more than 30,000 mean fluorescence intensity (MFI) as positive and less than 3000 MFI as negative, were applied to select high-quality specific extension primers. Among 55 allele-specific primers, 44 primers could be initially selected as optimal primer. Through adjusting the length, six primers were improved. The other failed five primers were corrected by refractory modification. MICA genotypes by ASPE on microarrays showed the same results as those by nucleotide sequencing. On the basis of these results, ASPE on microarrays may provide high-throughput genotyping for MICA alleles for population studies, disease-gene associations and HSCT.
Assuntos
Alelos , Técnicas de Genotipagem , Antígenos de Histocompatibilidade Classe I/classificação , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Primers do DNA/química , Genótipo , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Reação em Cadeia da Polimerase/métodos , Polimorfismo GenéticoRESUMO
INTRODUCTION: Intersphincteric resection (ISR) is the ultimate anal-sparing technique as an alternative to abdominoperineal resection in selected patients. Oncological safety is still debated. This study analyses long-term oncological results and evaluates risk factors for local recurrence (LR) and overall survival (OS) after minimally-invasive ISR. MATERIALS AND METHODS: Retrospective single-center data were collected from a prospectively maintained colorectal database. A total of 161 patients underwent ISR between 2008 and 2018. OS and local recurrence-free survival (LRFS) were assessed using Kaplan-Meier analysis (log-rank test). Risk factors for OS and LRFS were assessed with Cox-regression analysis. RESULTS: Median follow-up was 55 months. LR occurred in 18 patients. OS and LRFS rates at 1, 3, and 5 years were 96%, 91%, and 80% and 96%, 89%, and 87%, respectively. Tumor size (p = 0.035) and clinical T-stage (p = 0.029) were risk factors for LRFS on univariate analysis. On multivariate analysis, tumor size (HR 2.546 (95% CI: 0.976-6.637); p = 0.056) and clinical T-stage (HR 3.296 (95% CI: 0.941-11.549); p = 0.062) were not significant. Preoperative CEA (p < 0.001), pathological T-stage (p = 0.033), pathological N-stage (p = 0.016) and adjuvant treatment (p = 0.008) were prognostic factors for OS on univariate analysis. Preoperative CEA (HR 4.453 (95% CI: 2.015-9.838); p < 0.001) was a prognostic factor on multivariate analysis. CONCLUSIONS: This study confirms the oncological safety of minimally-invasive ISR for locally advanced low-lying rectal tumors when performed in experienced centers. Despite not a risk factor for LR, tumor size and, locally advanced T-stage with anterior involvement should be carefully evaluated for optimal surgical strategy. Preoperative CEA is a prognostic factor for OS.
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Adenocarcinoma/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Protectomia/métodos , Neoplasias Retais/cirurgia , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Idoso , Canal Anal , Antígeno Carcinoembrionário/sangue , Quimiorradioterapia Adjuvante , Feminino , Hospitais com Alto Volume de Atendimentos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Análise Multivariada , Terapia Neoadjuvante , Tratamentos com Preservação do Órgão/métodos , Neoplasias Retais/sangue , Neoplasias Retais/patologia , Fatores de Risco , Taxa de Sobrevida , Carga TumoralRESUMO
Single nucleotide polymorphisms of minor histocompatibility antigens (mHags) have been genotyped by allele-specific polymerase chain reaction with sequence-specific primers (PCR-SSP). Because discriminating the genotype of HB-1 Y by PCR-SSP under various PCR conditions was difficult, we optimized the use of oligonucleotides complementary to the allele-specific forward primer to improve the specificity of the HB-1 Y PCR-SSP. Specific allele discrimination was possible with an annealing temperature between 61°C and 63°C and in the presence of a threefold excess of a 15-bp complementary oligonucleotide. In conclusion, the inclusion of a complementary oligonucleotide in the PCR-SSP assay may improve its specificity and selectivity for genotyping several mHags for which optimizing PCR conditions have been difficult.
Assuntos
Alelos , Primers do DNA/genética , Antígenos HLA-B/genética , Reação em Cadeia da Polimerase/métodos , Primers do DNA/imunologia , Genótipo , Antígenos HLA-B/imunologia , Humanos , Antígenos de Histocompatibilidade Menor , Sensibilidade e EspecificidadeRESUMO
AIM: Colorectal cancer is associated with inflammatory bowel disease. The mechanisms of how different genetic make-ups of cytokines might influence the individual susceptibility to develop particular types of tumours are still unknown. The authors analysed the association between genetic polymorphisms in cytokine/cytokine receptor genes and the risk of colorectal cancer in a Korean population. METHOD: The authors assessed polymorphisms of the interleukin: IL-1, IL-1R, IL-2, IL-4, IL-4R, IL-10, transforming growth factor (TGF)-ß1, IFN-γ genes in Korean patients with colorectal cancer (n = 170) and in a normal healthy control group (n = 130) to investigate the association between theses cytokine gene polymorphisms and the risk of colorectal cancer. RESULTS: The IL-4R 1902*T allele was found to be associated with an increased risk of colon cancer (P < 0.01, OR = 2.0) and rectal cancer (P < 0.05, OR = 1.8). The IL-4R 1902*C allele was associated with a decreased risk of both colon cancer (P < 0.01, OR = 0.51) and rectal cancer (P < 0.05, OR = 0.5). The TFG-ß1 10*T allele was found to be associated with an increased risk of colon cancer (P < 0.00, OR = 2.3) and the TFG-ß1 10*C allele with a decreased risk of colon cancer (P < 0.00, OR = 0.43). CONCLUSION: These results suggest that the genetic polymorphisms of IL-4R and TGF-ß1 are associated with the risk of colorectal cancer in a Korean population.
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Neoplasias Colorretais/genética , Receptores de Interleucina-4/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-1/genética , Interleucina-10/genética , Interleucina-2/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fator de Crescimento Transformador beta1/genéticaRESUMO
Minor histocompatibility antigens (mHags) are polymorphic peptides presented to T lymphocytes restricted by the MHC molecule. It has been reported that disparities of mHags are a potential risk factor for GVHD after hematopoietic SCT (HSCT). Here we observed allelic frequencies of HA-1, -2 and -8 in 139 Korean healthy individuals using PCR-sequence-specific primers, and analyzed the correlation between disparity of these mHags and acute GVHD (aGVHD) in 54 patients who underwent HSCT from unrelated HLA-identical donors. The allelic frequencies in Korean healthy individuals were 39.6 and 60.4% for HA-1(H) and HA-1(R), 92.4 and 7.6% for HA-2(M) and HA-2(V), 36.7 and 63.3% for HA-8(R) and HA-8(P), respectively. The frequencies of mHags incompatibility known to be associated with aGVHD were 16.7% in HA-1, 0% in HA-2 and 25.9% in HA-8. However, the statistically significant association of aGVHD with these mHags incompatibility was not found between healthy donors and leukemia patients after unrelated HSCT. This first report about mHags in Koreans may be helpful in further defining the clinical impact of mHags disparities in HSCT and in comparing with other populations.
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Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Antígenos de Histocompatibilidade Menor/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Frequência do Gene , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Coreia (Geográfico)/epidemiologia , Leucemia/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Oligopeptídeos/genética , Doadores de Tecidos/estatística & dados numéricosRESUMO
The combination effects of minocycline (MC), a second-generation tetracycline compound and pyruvate (PY), a glycolysis end metabolite with antioxidant activity were investigated in the rat striatum following an excitotoxic insult. Striatal injection of quinolinic acid (QUIN) resulted in marked inflammation characterized by microgliosis, astrogliosis and enhanced expressions of pro-inflammatory enzymes inducible nitric oxide synthase and cyclooxygenase-2. Inflammatory responses were attenuated with administration of either MC or PY, however, the combination of both compounds was significantly more effective in reducing inflammation relative to MC or PY applied alone. Immunohistochemical analysis at 7 days post-intrastriatal QUIN injection showed extensive oxidative stress evident as lipid peroxidation, oxidative DNA damage and reactive oxygen species formation which was partially decreased by each agent applied separately but markedly inhibited with the combination of the two compounds. In addition, combination treatments significantly reduced neuronal loss in QUIN-injected striatum compared with the agents applied separately. Furthermore, long-term combination treatment decreased striatal lesions and inflammation after QUIN injection. These results demonstrate that MC and PY confer a considerably enhanced anti-inflammatory and neuroprotective efficacy when applied together and suggest this combinatorial procedure as a novel therapeutic strategy in neurodegenerative disorders such as Huntington's disease which exhibit excitotoxic insults.
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Doença de Huntington/tratamento farmacológico , Inflamação/tratamento farmacológico , Minociclina/uso terapêutico , Neurônios/efeitos dos fármacos , Ácido Pirúvico/uso terapêutico , Análise de Variância , Animais , Western Blotting/métodos , Morte Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Sinergismo Farmacológico , Doença de Huntington/induzido quimicamente , Doença de Huntington/patologia , Doença de Huntington/fisiopatologia , Imuno-Histoquímica/métodos , Inflamação/etiologia , Masculino , Proteínas do Tecido Nervoso/metabolismo , Neurônios/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácido Quinolínico/toxicidade , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fatores de TempoRESUMO
Recent work from this laboratory has demonstrated that purinergic-mediated depolarization of human microglia inhibited a store-operated pathway for entry of Ca2+. We have used Fura-2 spectrofluorometry to investigate the effects on store-operated Ca2+ influx induced by replacement of NaCl with Na-gluconate in extracellular solutions. Three separate procedures were used to activate store-operated channels. Platelet activating factor (PAF) was used to generate a sustained influx of Ca2+ in standard physiological saline solution (PSS). The magnitude of this response was depressed by 70% after replacement of PSS with low Cl- PSS. A second procedure used ATP, initially applied in Ca2+-free PSS solution to deplete intracellular stores. The subsequent perfusion of PSS solution containing Ca2+ resulted in a large and sustained entry of Ca2+, which was inhibited by 75% with low Cl- PSS. The SERCA inhibitor cyclopiazonic acid (CPA) was used to directly deplete stores in zero-Ca2+ PSS. Following the introduction of PSS containing Ca2+, a maintained stores-operated influx of Ca2+ was evident which was inhibited by 77% in the presence of the low Cl- PSS. Ca2+ influx was linearly reduced with cell depolarization in elevated K+ (7.5 to 35 mM) suggesting that changes in external Cl- were manifest as altered electrical driving force for Ca2+ entry. However, 50 mM external KCl effectively eliminated divalent entry which may indicate inactivation of this pathway with high magnitudes of depolarization. Patch clamp studies showed low Cl-PSS to cause depolarizing shifts in both holding currents and reversal potentials of currents activated with voltage ramps. The results demonstrate that Cl- channels play an important role in regulating store-operated entry of Ca2+ in human microglia.
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Sinalização do Cálcio , Cálcio/metabolismo , Canais Iônicos/fisiologia , Microglia/metabolismo , Trifosfato de Adenosina/farmacologia , Ânions/metabolismo , Soluções Tampão , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Células Cultivadas , Embrião de Mamíferos , Inibidores Enzimáticos/farmacologia , Espaço Extracelular/metabolismo , Gluconatos/farmacologia , Humanos , Indóis/farmacologia , Técnicas de Patch-Clamp , Fator de Ativação de Plaquetas/farmacologia , Potássio/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Cloreto de Sódio/farmacologiaRESUMO
Erythropoietin (EPO) is a hematopoietic growth factor that stimulates proliferation and differentiation of erythroid precursor cells and is also known to exert neurotrophic activity in the central nervous system (CNS). However, little is known about expression of EPO and EPO receptor (EPOR) in human CNS tissues. In the present study, we investigated the effects of proinflammatory cytokines on EPO and EPOR expression in highly purified cultures of human neurons, astrocytes, microglia, and oligodendrocytes using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). EPO mRNA was demonstrated only in human astrocytes, while EPOR expression was found in human neurons, astrocytes, and microglia. Neither EPO nor EPOR expression was found in oligodendrocytes. In human astrocytes, EPO mRNA and secreted EPO protein levels were downregulated after exposure to proinflammatory cytokines (IL-1beta, IL-6, or TNF-alpha). In human neurons, TNF-alpha treatment markedly increased EPOR expression. These results suggest that proinflammatory cytokines regulate expression of EPO and EPOR in human neurons, astrocytes, and microglia and further facilitate interactions among different cell types in the human CNS.
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Astrócitos/metabolismo , Eritropoetina/biossíntese , Microglia/metabolismo , Neurônios/metabolismo , Oligodendroglia/metabolismo , Receptores da Eritropoetina/biossíntese , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Células Cultivadas , Sistema Nervoso Central/citologia , Sistema Nervoso Central/embriologia , Sistema Nervoso Central/metabolismo , Citocinas/farmacologia , Ensaio de Imunoadsorção Enzimática , Eritropoetina/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Microglia/citologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Oligodendroglia/citologia , RNA Mensageiro/metabolismo , Receptores da Eritropoetina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
The effects of acute application of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) on levels of intracellular Ca(2+) ([Ca(2+)]i) and on whole-cell outward and inward K(+) currents were studied in cultured human microglia. TNFalpha elicited a linear increase in [Ca(2+)]i to a plateau level in microglia bathed in either standard physiological saline solution or Ca(2+)-free physiological saline solution. The rate of increase of [Ca(2+)]i or the level of [Ca(2+)]i attained was not significantly altered in the absence of external Ca(2+) indicating that Ca(2+) influx did not contribute appreciably to the cytokine-induced rise in [Ca(2+)]i. This point was directly confirmed using Mn(2+) quenching where no change in signal fluorescence was observed with TNFalpha treatment of microglia in Ca(2+)-free physiological saline solution. The rate of increase of [Ca(2+)]i induced by TNFalpha in Ca(2+)-free physiological saline solution was not altered by prior application of ATP to deplete inositol triphosphate stores indicating that these stores did not contribute to the cytokine response. In whole-cell patch clamp recordings, the acute treatment of human microglia with TNFalpha led to the expression of an outward K(+) current in one-third (14 of 41) of cells. This current was activated at potentials positive to -30 mV, showed rapid kinetics of activation with no evident inactivation and had an I-V relation exhibiting outward rectification. Analysis of tail currents showed reversal of the outward K(+) current near -70 mV and tetraethylammonium (10 mM) inhibited the outward K(+) current to 24% of control level. Acute application of TNFalpha had no effect to alter inward rectifier currents generated from voltage ramps. The signaling pathways involving TNFalpha modulation of [Ca(2+)]i and K(+) channels in human microglia may contribute to functional and pathological actions of the cytokine in the brain.
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Canais de Cálcio/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Encefalite/metabolismo , Líquido Intracelular/efeitos dos fármacos , Microglia/efeitos dos fármacos , Canais de Potássio/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Cálcio/deficiência , Canais de Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Relação Dose-Resposta a Droga , Encefalite/fisiopatologia , Inibidores Enzimáticos/farmacologia , Feto , Humanos , Indóis/farmacologia , Líquido Intracelular/metabolismo , Manganês/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Microglia/metabolismo , Microscopia de Fluorescência , Técnicas de Patch-Clamp , Canais de Potássio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Espectrometria de Fluorescência , Tetraetilamônio/farmacologiaRESUMO
We examined the distribution of polymorphic elements within the tumor necrosis factor (TNF) gene cluster in 133 normals and in 20 Korean families and compared our data with the results of Caucasians. The genotypes that are shown frequently are TNF a6 (33.8%), TNF b5 (46.6%), TNF c1 (79.3%), TNF d3 (34.6%), TNF e3 (86.5%), TNFB*2 (51.5%), and TNF(-308) A (91.4%). In comparison, TNFa 6 (33.8%), TNFa 13 (4.1%), TNFb 5 (46.6%), TNFd 1 (7.5%), TNFd 3 (34.6%), TNFe 3 (86.5%), TNFe 4 (6.8%), and TNF(-308) A (91.3%) were found more frequently in Koreans than Caucasians (p < 0.01). TNFa 14, TNFa 15, TNFd 8, and TNFe 4 alleles were found only in Korean controls. However, TNFb 6 and TNFb 7 alleles were not found in this study. From the TNF gene of TNFa, TNFb, TNFc, TNFn, TNF(-308), TNFd, and TNFe, 49 different TNF haplotypes were found in 20 Korean families. These data suggest that the TNF microsatellite haplotypes constitute a highly polymorphic system and that will provide useful information on the association between the TNF marker and the immune disease.
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Haplótipos/imunologia , Família Multigênica/imunologia , Polimorfismo de Fragmento de Restrição , Fator de Necrose Tumoral alfa/genética , Alelos , Povo Asiático/genética , Família , Marcadores Genéticos/imunologia , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Coreia (Geográfico)RESUMO
To evaluate the association of TNFB NcoI polymorphism with SLE in the Korean population, we investigated the frequencies of the TNFB and HLADRB1 alleles in 281 controls and 97 SLE patients, including 56 patients with nephritis and 41 patients without nephritis. The frequency of the TNFB*2 homozygote in SLE was significantly increased over controls (43.3% vs 28.5%, RR = 1.9,p < 0.01). In SLE with nephritis, the TNFB*2 homozygote was more significantly increased (57.1% vs 28.5%, RR = 3.4,p < 0.0001), whereas there was no significant difference between SLE without nephritis and controls. The study of HLA-DRB 1 alleles revealed the increased frequencies of DRB1*02 and *03 (30.9% vs 18.2%, RR = 2.0,p < 0.01; 8.2% vs 2.1%, RR = 4.1,p < 0.05). There was no significantly different distribution of HLA-DRB1 alleles between SLE patients with nephritis and without nephritis. We found positive LD between TNFB*1 and HLA-DR1B1*13, and between TNFB*2 and the particular DRB1 allele: *15, *04, and *07 in controls and/or in SLE patients. After stratification for each HLADRB1 allele, SLE with nephritis showed a higher frequency of TNFB*2 homozygote compared with the corresponding controls in DRB1*15, *08, and *09 positives. Our results suggest that the TNFB*2 homozygote may be a strong susceptibility gene of SLE with nephritis in the Korean population.
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Doenças Autoimunes/genética , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Linfotoxina-alfa/genética , Alelos , Povo Asiático/genética , Doenças Autoimunes/epidemiologia , Canadá/epidemiologia , Suscetibilidade a Doenças , Feminino , Alemanha/epidemiologia , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Homozigoto , Humanos , Coreia (Geográfico)/epidemiologia , Desequilíbrio de Ligação , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/epidemiologia , Masculino , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , População Branca/genéticaRESUMO
We have characterized the profile of membrane currents in an immortalized human neural stem cell line, HB1.F3 cells, using whole-cell patch clamp technique. Human neural stem cell line generated from primary cell cultures of embryonic human telencephalon using a replication-incompetent retroviral vector containing v-myc expresses nestin, a cell type-specific marker for neural stem cells. The human neural stem cells expressed both outward and inward K(+) currents with no evidence for Na(+) currents. The density of the outward, delayed rectifying type K(+) current was 1.8 +/- 0.015 nA/pF, and that of the inwardly rectifying K(+) current was 0.37 +/- 0.012 nA/pF (at 30 mM of [K(+)](o)). In order to induce neuronal differentiation of the neural stem cells, a full-length coding region of NeuroD, a neurogenic transcription factor, was transfected into HB1.F3 cells. Introduction of NeuroD induced expression of Na(+) currents with the current density of 0.042 +/- 0.011 nA/pF. The presence of two types of K(+) currents and expression of Na(+) currents induced by NeuroD appear to reflect the characteristic physiological features of human neural stem cells.
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Neurônios/fisiologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/fisiologia , Células-Tronco/fisiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Células Cultivadas , Eletrofisiologia , Embrião de Mamíferos , Humanos , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Proteínas do Tecido Nervoso/farmacologia , Proteínas do Tecido Nervoso/fisiologia , Canais de Sódio/fisiologia , Células-Tronco/efeitos dos fármacos , Telencéfalo/citologia , Telencéfalo/efeitos dos fármacos , Telencéfalo/fisiologia , Transfecção/métodosRESUMO
OBJECTIVE: To investigate the association of HLA class II alleles with the susceptibility to sudden sensorineural hearing loss and with the results of corticosteroid treatment in the Korean population. DESIGN: HLA-DRB1, -DQA1, -DQB1, and -DPB1 genotyping by the sequence-specific oligonucleotide probes method in 41 patients with sudden sensorineural hearing loss and in 206 healthy control subjects. Initial hearing levels at the onset of hearing loss and final hearing levels after treatment were evaluated for the association with HLA class II alleles. SETTING: Tertiary care referral center, ambulatory and hospitalized care. SUBJECTS: Forty-one patients (24 men and 17 women; mean age, 49.2 years) were compared with 206 controls. Patients were divided into 2 groups according to their response to corticosteroid therapy (good response vs nonresponse). RESULTS: The frequencies of HLA-DRB1, -DQA1, -DQB1, and -DPB1 alleles were not significantly different between patients and controls (P>.05). When an association between the results of corticosteroid treatment and the frequency of HLA alleles was evaluated, the frequencies of HLA-DRB1*14 (relative risk [RR] = 3.5, P<.02), -DQA1*03 (RR = 4.2, P<.02), and -DQA1*05 (RR = 3.1, P<.03) were significantly increased, but HLA-DQA1*01 (RR = 0.2, P<.004) and -DQB1*06 (RR = 0.2, P<.009) were decreased in the group nonresponsive to corticosteroid therapy, compared with the controls. The distribution of HLA-DQA1*01 (P<.04), -DQB1*06 (P<.02), and -DQA1*03 (P<.003) was significantly different between the responsive and the nonresponsive groups. HLA-DQA1 allelic combination analysis showed that the frequencies of DQA1*03 and *05 had a high RR value in patients with sudden sensorineural hearing loss (RR = 4.1, P<.003) and in patients in the nonresponsive group (RR = 8.9, P<.001), compared with the controls. CONCLUSION: The presence of HLA class II alleles may be a useful genetic marker in forecasting a prognosis in Korean patients with sudden sensorineural hearing loss.
Assuntos
Alelos , Glucocorticoides/uso terapêutico , Antígenos HLA-D/genética , Perda Auditiva Neurossensorial/genética , Perda Auditiva Súbita/genética , Prednisona/uso terapêutico , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Súbita/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do TratamentoAssuntos
Antígenos HLA/genética , Leucemia Mieloide/genética , Reação em Cadeia da Polimerase/métodos , Quimeras de Transplante/genética , Doença Aguda , Adulto , Criança , Estudos de Viabilidade , Feminino , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Teste de Histocompatibilidade/métodos , Humanos , Leucemia Mieloide/imunologia , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Sensibilidade e Especificidade , Quimeras de Transplante/imunologiaAssuntos
Alelos , Cromossomos Humanos Par 6/genética , Cisteína Endopeptidases , Complexos Multienzimáticos , Proteínas/genética , Povo Asiático/genética , Sequência de Bases , Frequência do Gene , Humanos , Coreia (Geográfico) , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Complexo de Endopeptidases do Proteassoma , Alinhamento de Sequência , Homologia de Sequência do Ácido NucleicoAssuntos
Alelos , Doenças Autoimunes/genética , Genes MHC da Classe II , Antígenos HLA-D/genética , Antígenos de Histocompatibilidade Classe II , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Povo Asiático/genética , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Sequência de Bases , Éxons/genética , Humanos , Coreia (Geográfico)/epidemiologia , Dados de Sequência Molecular , Polimorfismo Conformacional de Fita Simples , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Espondilite/genética , Espondilite/imunologia , Tireoidite Autoimune/genética , Tireoidite Autoimune/imunologiaRESUMO
Interactions between killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen class I ligands influence the development of the natural killer cell repertoire and the responses to infection, cancer, and allogeneic tissue. In this study, the association of KIR genes with acute graft-vs-host disease (GVHD) was investigated in 44 pairs of leukemia patients and their unrelated donors for hematopoietic stem cell transplantation (HSCT). Donors with more than 12 KIR genes showed significantly decreased frequencies of severe acute GVHD compared with donors with less than 11 KIR genes (P < 0.05). The distribution of KIR genotypes was not different between severe and mild acute GVHD in patients and donors, respectively. These results suggest that the number of KIR genes in donors could influence the occurrence of acute GVHD after unrelated HSCT.