RÉSUMÉ
Objective: To establish the threshold value of human leukocyte antigen (HLA) mixed antigen reagent screening test results, and to verify it by HLA single antigen reagent confirmation test results. Methods: The results of 2 255 serum samples tested for HLA antibodies by HLA mixed antigen reagent in the department of HLA Laboratory, the First Affiliated Hospital of Soochow University from October 2017 to December 2021 were retrospectively analyzed. Among them, 1 139 samples were also tested by single antigen HLA Class-â reagent and 1 116 samples were also tested by single antigen HLA Class-â ¡ reagent. Based on the same antigens coated with both reagents, the Mean Fluorescence Intensity (MFI) and Nomalized Background ratio (NBG ratio) of 12 HLA Class-â beads and 5 HLA Class-â ¡ beads in the HLA mixed antigen reagent and the MFI of 77 anti-HLA class-â antibodies and 35 anti-HLA class-â ¡ antibodies detected by HLA single antigen reagent were recorded. The MFI and NBG ratio of HLA mixed antigen reagent beads in 1 139 or 1 116 samples were segmented according to the positive rate of antibodyies detected by the single antigen reagent corresponding to the antigens coated with each HLA mixed antigen reagent bead, and the results of the HLA mixed antigen screening test were verified by the HLA single antigen reagent confirmation test. Results: The threshold values of MFI and NBG ratio of HLA mixed antigen reagent's 17 beads were established. The MFI of No. 1 to No. 17 beads of HLA mixed antigen reagent ranged from 26.86 to 21 925.58, and the NBG ratio ranged from 0 to 434.65. According to the positive detection rate of HLA single antigen reagent corresponding to the coated antigens, the MFI and NBG ratio of the beads of HLA mixed antigen reagent were divided into positive interval, suspicious positive interval, suspicious negative interval and negative interval. The positive rates of anti-HLA class-â antibodies by HLA mixed antigen reagent and single antigen HLA Class-â reagent were 87.5% (997/1 139) and 66.3% (755/1 139). The positive rates of anti-HLA class-â ¡ antibodies were 63.4% (707/1 116) and 44.9% (501/1 116). In the samples with suspicious negative, suspicious positive and positive results of HLA class-â ãâ ¡ antibodies detected by HLA mixed antigen reagent, the positive detection rates of single antigen HLA Class-â reagent were 14.9% (17/114), 41.3% (145/351) and 91.3% (590/646), respectively. The positive detection rates of single antigen HLA Class-â ¡ reagent were 15.5% (58/375), 26.5% (81/306) and 88.8% (356/401), respectively. Conclusions: In this study, the threshold values of MFI and NBG ratio of HLA mixed antigen reagent screening test are established, and the threshold values are verified by the results of HLA single antigen reagent confirmation test. HLA mixed reagent screening test can be used for screening of HLA antibodies, and if necessary, it should be combined with HLA single antigen confirmatory test for clinical detection of HLA antibodies.
Sujet(s)
Antigènes HLA , Antigènes d'histocompatibilité de classe II , Humains , Indicateurs et réactifs , Études rétrospectives , Test d'histocompatibilité/méthodes , Antigènes d'histocompatibilité de classe I , Alloanticorps , Rejet du greffonRÉSUMÉ
OBJECTIVE: Linezolid is commonly used in intensive care units (ICU) but has the potential to interact with other drugs. This study aimed to evaluate the prevalence of potential drug-drug interactions in ICU patients receiving linezolid. PATIENTS AND METHODS: Data of ICU patients receiving linezolid were extracted and included in the Hospital Prescription Analysis Program of China, and the risk of potential drug-drug interactions between concomitant drugs and linezolid was evaluated using the Lexicomp database. RESULTS: A total of 3,712 ICU patients from 59 hospitals were included in the analysis, and patients received an average of 17 concomitant drugs. A total of 67.9% of patients had potential drug-drug interactions. Patients receiving concomitant drugs with risk ratings of "X", "D", and "C" categories were 20.8%, 30.4%, and 35.1%, respectively. Opioids were the most frequently prescribed drug class with drug-drug interactions (DDIs) in the "X" category, whereas butorphanol, metoclopramide, and sufentanil were the most contraindicated concomitant drugs. CONCLUSIONS: ICU patients receiving linezolid have a high prevalence of potential drug-drug interactions, and efforts should be made to better recognize and manage this risk.
Sujet(s)
Unités de soins intensifs , Humains , Linézolide/effets indésirables , Études transversales , Prévalence , Interactions médicamenteusesRÉSUMÉ
Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1â¶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.
Sujet(s)
Syndrome coronarien aigu , Fibrillation auriculaire , Accident vasculaire cérébral ischémique , Infarctus du myocarde , Intervention coronarienne percutanée , Accident vasculaire cérébral , Humains , Fibrillation auriculaire/complications , Fibrillation auriculaire/traitement médicamenteux , Antiagrégants plaquettaires/usage thérapeutique , Antiagrégants plaquettaires/effets indésirables , Syndrome coronarien aigu/complications , Syndrome coronarien aigu/traitement médicamenteux , Fibrinolytiques/usage thérapeutique , Études rétrospectives , Résultat thérapeutique , Anticoagulants , Infarctus du myocarde/complications , Hémorragie , Accident vasculaire cérébral ischémique/complications , Accident vasculaire cérébral ischémique/traitement médicamenteuxRÉSUMÉ
Population ageing has become a major social issue of concern worldwide in recent years, with significant implications for national economic and social development. Globally, Singapore is one of the first countries to address ageing as a population issue and has implemented relatively well-developed initiatives to promote healthy ageing. Similar to China, Singapore has a sharp decline in the total fertility rate, resulting in changes in the population structure. This paper briefly introduces Singapore's healthy ageing measures, summarizes Singapore's practical measures and coping concepts in scientific research on ageing, healthcare programs for the elderly, elderly -friendly environment construction, artificial intelligence big data application, and puts forward that China should pay attention to the effectiveness of population growth incentive measures, pay attention to the scientific and technological response, increase the development and application of artificial intelligence, improve primary health care and long-term health care, and update scientific concepts.
Sujet(s)
Vieillissement en bonne santé , Sujet âgé , Intelligence artificielle , Chine , Humains , Politique (principe) , SingapourRÉSUMÉ
BACKGROUND: The rampant spread of the novel coronavirus disease (COVID-19) has assumed pandemic proportions across the world. Attempts to contain its spread have entailed varying early screening and triage strategies implemented in different countries and regions. AIM: To share the experience of scientific and standardized management of fever clinics in China, which provide the first effective checkpoint for the prevention and control of COVID-19. INTRODUCTION: A fever clinic was established at our hospital in Tianjin, China, for initially identifying suspected cases of COVID-19 and controlling the spread of the disease. METHODS: The management system covered the following aspects: spatial layout; partitioning of functional zones; a work management system and associated processes; management of personnel, materials and equipment; and patient education. RESULTS: Within two months of introducing these measures, there was a comprehensive reduction in the number of new COVID-19 cases in Tianjin, and zero infections occurred among medical staff at the fever clinic. DISCUSSION: The fever clinic plays an important role in the early detection, isolation and referral of patients presenting with fevers of unknown origin. Broad screening criteria, an adequate warning mechanism, manpower reserves and staff training at the clinic are essential for the early management of epidemics. CONCLUSION: The spread of COVID-19 has been effectively curbed through the establishment of the fever clinic, which merits widespread promotion and application. IMPLICATIONS FOR NURSING AND HEALTH POLICIES: Health managers should be made aware of the important role of fever clinics in the early detection, isolation and referral of patients, and in the treatment of infectious diseases to prevent and control their spread. In the early stage of an epidemic, fever clinics should be established in key areas with concentrated clusters of cases. Simultaneously, the health and safety of health professionals require attention.
Sujet(s)
Établissements de soins ambulatoires/organisation et administration , COVID-19/soins infirmiers , Fièvre d'origine inconnue/soins infirmiers , Pneumopathie virale/soins infirmiers , COVID-19/épidémiologie , Chine/épidémiologie , Conception et construction de locaux , Fièvre d'origine inconnue/épidémiologie , Fièvre d'origine inconnue/virologie , Humains , Pandémies , Pneumopathie virale/épidémiologie , Pneumopathie virale/virologie , SARS-CoV-2RÉSUMÉ
Objective: To explore the effects of endoplasmic reticulum stress-induced apoptosis in thyroid injury of rats caused by excessive fluoride intake. Methods: All 40 Wistar rats were randomly divided into four groups, control group, low fluoride group, medium fluoride group and high fluoride group. The rats in control group were fed with tap water (fluoride concentration=0.344 mg/L) and the experimental rats were fed with the water contaminated fluoride with the dose of 5, 10 and 20 mg/L. 10 rats (female: male=1â¶1) in each group were sacrificed after 8 months of exposure through drinking water. The contents of urine fluoride were detected by fluorine ion selective electrode method. Morphology of thyroid was observed through light microscope and apoptosis in thyroid were detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The mRNA and protein expressions of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were analyzed by RT-PCR and immunohistochemistry respectively, and results were compared among groups. Results: The contents of urine fluoride in all fluoride treated groups were separately (4.74±1.88), (7.70±2.82) and (10.50±2.92) mg/L, which were gradually higher than that of control group (2.23±0.54) mg/L (P<0.05). Morphological changes were found in thyroid tissues of fluoride treated groups, thyroid follicular hyperplasia or even no cavity cell clusters were observed. Apoptosis in thyroid were notably increased in fluoride treated groups. The mRNA expression levels of GRP78 in all fluoride treated groups were separately 1.30±0.42, 1.39±0.29 and 1.50±0.27, which were significantly higher than that of control group (0.93±0.24) (P<0.05). And the mRNA expression levels of CHOP in medium and high fluoride groups were separately 1.17±0.29 and 1.30±0.26, which were significantly higher than that of control group (0.91±0.20) (P<0.05). The protein expression levels of GRP78 and CHOP in medium and high fluoride groups were respectively 29.68±4.04, 29.90±3.74 and 4.05±1.62, 4.44±1.81, which were significantly higher than those in the control group (separately 23.80±6.36, 2.27±0.89) (P<0.05). Conclusion: Excessive-fluoride intake can induce thyroid injury, and endoplasmic reticulum stress-induced apoptosis might be involved in the injury.
Sujet(s)
Apoptose , Stress du réticulum endoplasmique , Fluorures/toxicité , Glande thyroide/traumatismes , Animaux , Femelle , Mâle , Répartition aléatoire , Rat WistarRÉSUMÉ
The treatment for laryngopharyngeal reflux diseases consist of general treatment, medical therapy and surgical treatment, among which, drug therapy is still the main effective way. Proton pump inhibitor is adopted as the first drug for patients with laryngopharyngeal reflux disease only caused by acid reflux. With standardized treatment, the majority of symptoms in laryngopharyngeal reflux disease could be alleviated effectively. PPI therapy, while seeming logical, is less useful in patients with reflux hypersensitivity, weak acid or non acid reflux, neuropsychic factors and gastroesophageal reflux disease. This article aims to investigate bewilderment and challenge faced by clinicians when managing adult laryngology reflux disease with medical therapy.
Sujet(s)
Reflux laryngopharyngé/traitement médicamenteux , Inhibiteurs de la pompe à protons/usage thérapeutique , Adulte , Femelle , Reflux gastro-oesophagien/complications , Reflux gastro-oesophagien/traitement médicamenteux , Reflux gastro-oesophagien/chirurgie , Humains , Reflux laryngopharyngé/étiologie , Reflux laryngopharyngé/chirurgie , MâleRÉSUMÉ
Aldolase is a key enzyme involved in glycolysis, gluconeogenesis, and the pentose phosphate pathway. To establish the expression patterns of all three aldolase isozyme genes in different tissues and during early embryogenesis in lower vertebrates, as well as to explore the functional differences between these three isozymes, the grass carp was selected as a model owing to its relatively high glucose-metabolizing capability. Based on the cDNA sequences of the aldolase A, B, and C genes, the expression patterns of these three isozymes were analyzed in different tissues and during early embryogenesis using quantitative real-time polymerase chain reaction (qRT-PCR). Sequence analysis of cDNAs indicated that aldolase A, B, and C (GenBank accession numbers: KM192250, KM192251, and KM192252) consist of 364, 364, and 363 amino acids, respectively. The qRT-PCR results showed that the expression levels of aldolase A, B, and C were highest in the muscle, liver, and brain, respectively. Aldolase A and C exhibited similar expression patterns during embryogenesis, with high levels observed in unfertilized and fertilized eggs and at the blastocyst stage, followed by a decline and then increase after organogenesis. In contrast, aldolase B transcript was not detected during the unfertilized egg stage, and appeared only from gastrulation; the expression increased markedly during the feeding period (72 h after hatching), at which point the level was higher than those of aldolase A and C. These data suggest that the glucose content of grass carp starter feed should be adjusted according to the metabolic activity of aldolase B.
Sujet(s)
Carpes (poisson)/génétique , Protéines de poisson/génétique , Fructose bisphosphate aldolase/génétique , Régulation de l'expression des gènes au cours du développement , Animaux , Blastocyste/enzymologie , Blastocyste/métabolisme , Carpes (poisson)/embryologie , Carpes (poisson)/croissance et développement , Protéines de poisson/métabolisme , Fructose bisphosphate aldolase/métabolisme , Spécificité d'organeRÉSUMÉ
Total RNA isolated from the brain, muscle, liver, gonad, and intestinal tissues of grass carp was pooled to construct cDNA libraries. Using 454 pyrosequencing, a total of 738,604 high-quality reads were generated from the normalized cDNAs of the pooled individuals. Clustering and assembly of these reads produced a set of 37,086 all-unigene sequences after BLAST. Of these, 24,010 (64.74%) were annotated in the National Center for Biotechnology Information database, and 3715 simple sequence repeats and 2008 single nucleotide polymorphisms were identified in this EST dataset as potential molecular markers. This study provides new data for functional genomic and biological research on grass carp. The markers identified in this study will enrich the currently used molecular markers and facilitate marker-assisted selection in grass carp-breeding programs. These results also demonstrate that transcriptomic analysis based on 454 sequencing is a powerful tool for gene discovery and molecular marker development in non-model species.
Sujet(s)
Carpes (poisson)/génétique , ADN complémentaire/génétique , Polymorphisme de nucléotide simple , Analyse de séquence d'ADN/méthodes , Transcriptome , Animaux , Encéphale/métabolisme , Analyse de regroupements , Étiquettes de séquences exprimées , Femelle , Analyse de profil d'expression de gènes , Banque de gènes , Marqueurs génétiques , Gonades/métabolisme , Séquençage nucléotidique à haut débit , Muqueuse intestinale/métabolisme , Foie/métabolisme , Mâle , Répétitions microsatellites , Annotation de séquence moléculaire , Muscles/métabolismeRÉSUMÉ
Growth hormone releasing hormone (GHRH) regulates the secretion of growth hormone (GH) in the pituitary gland. A 66-bp deletion (c.-923_-858del) was detected in the 5'-flanking sequence of the largemouth bass (Micropterus salmoides) GHRH gene. In two cultured random populations of adult individuals (A: n = 170 and B: n = 150), the genotype ratios of +/+:+/- were 2.5:1 and 2.8:1 respectively. Only one -/- fish was detected. A Largemouth bass family was constructed with two heterozygous individuals (+/-) as parents. The genotype ratio of +/+:+/-:-/- in the filial generation embryos was 1:1.6:0.1 at the neurula and 1:2:0 at hatched larvae stages. This indicated that the 66-bp deletion was a recessive lethal site and that homozygous individuals (-/-) died off in embryonic development. The growth traits (body weight, body length and body depth) were measured, and the GHRH mRNA expression levels in brain tissue were detected using real-time PCR. The effects of genotype (+/-) on growth traits and GHRH mRNA expression were not significant. Although the cause of death was not clear, the results hint that the 66-bp deletion site in GHRH 5'-flanking sequence significantly affects the livability in largemouth bass embryonic development.
Sujet(s)
Séquence nucléotidique , Serran/génétique , Protéines de poisson/génétique , Hormone de libération de l'hormone de croissance/génétique , Délétion de séquence , Animaux , Serran/métabolisme , Protéines de poisson/métabolisme , Hormone de libération de l'hormone de croissance/métabolisme , Données de séquences moléculaires , Réaction de polymérisation en chaine en temps réel/médecine vétérinaireRÉSUMÉ
BACKGROUND: This study was to investigate the effects of the novel cannabinoid receptor - G protein-coupled receptor 55 (GPR55) - and its ligands O-1602 and cannabidiol (CBD) on gastrointestinal (GI) motility in rodents. METHODS: Lipopolysaccharide (LPS) was used in vivo to produce the model of septic ileus. The intestinal motility was measured by recording myoelectrical activity of jejunum in rats, and by measuring GI transit with a charcoal marker in mice, in presence of O-1602 or CBD. Inflammatory response was assessed serologically and histologically. The expression and distribution of GPR55 in the different parts of rat intestine were investigated by real-time PCR and immunohistochemistry. In vitro, the effects of the drugs on the GI movement were investigated by measuring the contraction of the intestinal muscle strips in organ bath, and the intracellular responses of the muscle cells with microelectrode technique. KEY RESULTS: G protein-coupled receptor 55 was expressed in different parts of rat intestine. Lipopolysaccharide significantly inhibited the intestinal motility, increased inflammatory cytokines and GPR55 expression. Pretreatment with CBD normalized LPS-induced hypomotility and improved the inflammatory responses serologically and histologically. Both O-1602 and CBD counteracted LPS-induced disturbances of the gut contraction, but had no effect on the membrane potential of the muscle cells, while cannabinoid type 1 receptor antagonist AM251 and cannabinoid type 2 receptor antagonist AM630 increased the potential. CONCLUSIONS & INFERENCES: G protein-coupled receptor 55 existed throughout the whole intestine of rats. O-1602 or CBD selectively normalized the motility disturbances. Possible mechanisms involved systemic anti-inflammation and the regulation of myoelectrical activity of the intestine.
Sujet(s)
Cannabidiol/analogues et dérivés , Cannabidiol/métabolisme , Motilité gastrointestinale/physiologie , Ligands , Récepteurs de cannabinoïdes/métabolisme , Récepteurs couplés aux protéines G/métabolisme , Animaux , Électromyographie , Motilité gastrointestinale/effets des médicaments et des substances chimiques , Transit gastrointestinal/effets des médicaments et des substances chimiques , Transit gastrointestinal/physiologie , Indoles/métabolisme , Inflammation/induit chimiquement , Inflammation/métabolisme , Interleukine-6/sang , Intestins/cytologie , Intestins/effets des médicaments et des substances chimiques , Intestins/anatomopathologie , Intestins/physiologie , Lipopolysaccharides/pharmacologie , Potentiels de membrane/physiologie , Souris , Souris de lignée C57BL , Myocytes du muscle lisse/physiologie , Pipéridines/métabolisme , Pyrazoles/métabolisme , Répartition aléatoire , Rats , Rat Sprague-Dawley , Récepteurs de cannabinoïdes/génétique , Facteur de nécrose tumorale alpha/sangRÉSUMÉ
In the present study, samples representing Orientobilharzia turkestanicum from cattle, sheep, and cashmere goat in Daqing District, Heilongjiang Province, China, were characterized and grouped genetically by sequences of mitochondrial cytochrome c oxidase subunit 1 gene (cox1) and nicotinamide adenine dinucleotide dehydrogenase subunit 1 gene (nad1). Genomic DNAs were extracted from parasites isolated from individual host by sodium dodecyl sulfate-protease K treatment. The cox1 and nad1 genes were amplified by polymerase chain reaction and then sequenced and compared with that of other members of the Schistosomatidae available in GenBank, and phylogenetic relationships between them were re-constructed using the neighbor-joining method. The results showed that the lengths of cox1 and nad1 sequences were 1,125 and 518 bp, respectively, for all O. turkestanicum samples sequenced. The identities of cox1 sequences of O. turkestanicum from cattle, sheep, and cashmere goat in Daqing, China with that of O. turkestanicum from sheep in Iran were 99.4%, 99.7%, and 99.8%, respectively. The identities of nad1 sequences of O. turkestanicum from cattle, sheep, and cashmere goat in Daqing, China with that of O. cheni from cashmere goat at Fuyu, Heilongjiang Province, China were 99.4%, 99.0%, and 100%, respectively. Phylogenetic analyses based on the cox1 and nad1 sequences revealed that O. turkestanicum is placed within the African schistosomes, and O. turkestanicum should be considered the sister species of Schistosoma spp.
Sujet(s)
Gènes de mitochondrie , Phylogenèse , Schistosomatidae/classification , Analyse de séquence d'ADN , Infections à trématodes/médecine vétérinaire , Animaux , Bovins/parasitologie , ADN des helminthes/analyse , Complexe I de la chaîne respiratoire/génétique , Complexe IV de la chaîne respiratoire/génétique , Capra/parasitologie , Données de séquences moléculaires , Schistosomatidae/génétique , Ovis/parasitologie , Infections à trématodes/parasitologieRÉSUMÉ
Critical interactions between the nervous system and the immune system during experimental autoimmune myasthenia gravis (EAMG) were examined in an animal model for human MG after immunization of adult female Lewis rats with Torpedo acetylcholine receptor (AChR) and complete Freund's adjuvant. Immunized rats depicted marked clinical severity of the disease. Using enzyme-linked immunospot (ELISPOT) assay and in situ hybridization techniques, immune responses in these animals were examined and showed elevated numbers of anti-AChR IgG secreting B cells and AChR reactive interferon (IFN)-gamma-secreting cells, enhanced mRNA expression of the proinflammatory cytokines IFN-gamma and tumour necrosis factor (TNF)-alpha as Th1 subset and the anti-inflammatory cytokines interleukin (IL)-4 and IL-10 as a Th2 subset, and transforming growth factor (TGF)-beta as a Th3 cytokine. Corticosterone and prostaglandin E(2) (PGE(2)) levels were measured by radioimmunoassay and illustrated increased production after immunization. Surgical denervation of the spleen reduced significantly the clinical severity of the disease, suppressed the numbers of IgG and IFN-gamma-secreting cells, down-regulated the mRNA expression for cytokines and reduced corticosterone and PGE(2) production. As controls, sham-operated rats were used and showed results as the EAMG non-denervated control rats. The data present herein, and for the first time, substantial effects of the nervous system on immune responses that may influence the outcome of EAMG. These effects were not dependent on cytokine inhibitory mediators such as prostaglandins or stress hormones. IL-10 and TGF-beta, the two potent immunosuppressive cytokines, were also suppressed, indicating a general suppression by splenic denervation. More investigations are initiated at our laboratories to understand the evident neural control over the immune system during challenges leading to the break of tolerance and development of autoimmunity, which may assist in innovative therapeutic approaches.
Sujet(s)
Dénervation/méthodes , Myasthénie auto-immune expérimentale/chirurgie , Rate/chirurgie , Animaux , Lymphocytes B/immunologie , Corticostérone/sang , Dinoprostone/immunologie , Femelle , Immunoglobuline G/immunologie , Interféron gamma/immunologie , Interleukine-4/immunologie , Myasthénie auto-immune expérimentale/immunologie , ARN messager/analyse , Rats , Rats de lignée LEW , Récepteurs cholinergiques/immunologie , Rate/innervation , Lymphocytes T/immunologie , Facteur de croissance transformant bêta/immunologie , Facteur de nécrose tumorale alpha/immunologieSujet(s)
Diabète expérimental/chirurgie , Transplantation d'ilots de Langerhans/immunologie , Transplantation d'ilots de Langerhans/physiologie , Glycoprotéines membranaires/génétique , Transplantation hétérologue/immunologie , Animaux , Ligand de Fas , Humains , Ilots pancréatiques/cytologie , Transplantation d'ilots de Langerhans/méthodes , Mâle , Souris , Souris de lignée C57BL , Souris transgéniques , Modèles animaux , Rats , Rat Sprague-Dawley , RT-PCR , Prélèvement d'organes et de tissus/méthodesRÉSUMÉ
We have identified and characterized N-Bak, a neuron-specific isoform of the pro-apoptotic Bcl-2 family member Bak. N-Bak is generated by neuron-specific splicing of a novel 20-base pair exon, which changes the previously described Bak, containing Bcl-2 homology (BH) domains BH1, BH2, and BH3, into a shorter BH3-only protein. As demonstrated by reverse transcription-polymerase chain reaction and RNase protection assay, N-Bak transcripts are expressed only in central and peripheral neurons, but not in other cells, whereas the previously described Bak is expressed ubiquitously, but not in neurons. Neonatal sympathetic neurons microinjected with N-Bak resisted apoptotic death caused by nerve growth factor (NGF) removal, whereas microinjected Bak accelerated NGF deprivation-induced death. Overexpressed Bak killed sympathetic neurons in the presence of NGF, whereas N-Bak did not. N-Bak was, however, still death-promoting when overexpressed in non-neuronal cells. Thus, N-Bak is an anti-apoptotic BH3-only protein, but only in the appropriate cellular environment. This is the first example of a neuron-specific Bcl-2 family member.
Sujet(s)
Épissage alternatif , Apoptose/physiologie , Variation génétique , Protéines membranaires/génétique , Neurones/physiologie , Protéines proto-oncogènes c-bcl-2/génétique , Séquence d'acides aminés , Animaux , Séquence nucléotidique , Encéphale/cytologie , Encéphale/physiologie , Cellules COS , Cellules cultivées , Chlorocebus aethiops , Cellules HeLa , Humains , Protéines membranaires/composition chimique , Protéines membranaires/métabolisme , Souris , Données de séquences moléculaires , Neurones/cytologie , Spécificité d'organe , Isoformes de protéines/composition chimique , Isoformes de protéines/génétique , Isoformes de protéines/métabolisme , Protéines proto-oncogènes c-bcl-2/composition chimique , Protéines proto-oncogènes c-bcl-2/métabolisme , Protéines recombinantes/métabolisme , Alignement de séquences , Similitude de séquences d'acides aminés , Ganglion cervical supérieur/cytologie , Ganglion cervical supérieur/physiologie , Transfection , Protéine Bak , Domaine d'homologie SRCRÉSUMÉ
The damage of acetylcholine receptor (AChR) at neuromuscular junctions of experimental autoimmune myasthenia gravis (EAMG), an animal model of human MG, is mediated by B cells which require T cell help. The Th2 associated cytokine IL-10 suppresses production of cytokines released by Th1 cells and is considered for treatment of human autoimmune diseases. To evaluate the role of IL-10 in EAMG, rhIL-10 was administered daily to Lewis rats by the subcutaneous route starting at the day of immunization and continued for 7 weeks. IL-10 failed to abrogate EAMG at low dose (0.1 or 1 microg/day) and at the dose of 3 microg/day caused earlier onset and aggravated clinical signs of EAMG when compared to EAMG rats injected with PBS only. Although Th1 responses reflected by AChR-induced lymphocyte proliferation and levels of IFN-gamma secreting cells, as well as AChR-induced Th1 cytokine mRNA expression was suppressed, augmented IL-4 mRNA expression and AChR-specific B cell responses may play an important role in the failure of IL-10 to abrogate EAMG. This study implicates a critical precaution in planning immunotherapy of IL-10 in antibody-mediated autoimmune diseases, e.g. MG.
Sujet(s)
Acétylcholine/immunologie , Lymphocytes B/immunologie , Interleukine-10/pharmacologie , Myasthénie auto-immune expérimentale/immunologie , Lymphocytes auxiliaires Th2/immunologie , Animaux , Lymphocytes B/effets des médicaments et des substances chimiques , Division cellulaire/immunologie , Femelle , Expression des gènes/immunologie , Humains , Immunoglobuline G/sang , Interleukine-10/génétique , Interleukine-10/immunologie , Faiblesse musculaire/immunologie , ARN messager/analyse , Rats , Rats de lignée LEW , Récepteurs cholinergiques/immunologie , Lymphocytes auxiliaires Th2/effets des médicaments et des substances chimiques , TorpedoRÉSUMÉ
OBJECTIVE: To provide bacteriological basis for curing infected root canals with sensitive drugs. METHODS: We have made bacterial cultivation for 56 cases with infected root canals and drug sensitive test with agar dilution. RESULTS: The rates of bacteria detection and positive rates from infected root canals were high. Anaerobia and aerobia were sensitive to different kinds of antibiotics. CONCLUSION: Bacteria have close relation to infected root canals. Sensitive drugs should be selected in clinical treatment.
RÉSUMÉ
The distributions and functions of NK cell subsets, as defined by the expression of Ly49 NK cell receptors, were examined in murine CMV (MCMV)-infected mice. MCMV induced a reduction in NK1.1+ cell number in the spleen and an increase in the peritoneal exudate cells. Within the splenic NK1.1+ population, proportional increases in Ly49A+ and Ly49G2+ cells but decreases in Ly49C+ and Ly49D+ cells were observed 3 days post-MCMV infection, but within the peritoneal NK1.1+ cell populations there were proportional decreases in Ly49A+ cells and increases in Ly49C+, Ly49D+, and Ly49G2+ cells. Lymphocytic choriomeningitis virus did not elicit a comparable NK cell subset distribution. Lymphokine-activated killer cells were sorted into different Ly49 NK cell subsets and adoptively transferred into C57BL/6 suckling mice. Regulation of MCMV synthesis in these suckling mice was shown to be an IFN-gamma-dependent, perforin- and Cmv-1-independent process, and each NK cell subset mediated anti-viral activity. In adult C57BL/6 mice, the control of MCMV in the spleen is mediated by a perforin-dependent mechanism, regulated in part by the Cmv-1 gene, which maps closely to the Ly49 family. In vivo depletions of either one or two of the Ly49 subsets in adult mice did not affect the ability of the residual NK cells to regulate MCMV synthesis. These data provide evidence of NK cell subset distribution and function in MCMV infection, but no individual subset was required for the Cmv-1-like regulation of MCMV synthesis.