An ITAM-signaling pathway controls cross-presentation of particulate but not soluble antigens in dendritic cells

Dendritic cells (DC) possess a unique capacity for presenting exogenous antigen on major histocompatibility class I, a process that is referred to as cross-presentation, which serves a critical role in microbial and tumor immunity. During cross-presentation, antigens derived from pathogen-infected or tumor cells are internalized and processed by DCs for presentation to cytotoxic T lymphocytes (CTLs). We demonstrate that a signaling pathway initiated by the immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptors DAP12 and FcRgamma utilizes the Vav family of Rho guanine nucleotide exchange factors (GEFs) for processing and cross-presentation of particulate, but not soluble, antigens by DCs. Notably, this novel pathway is crucial for processing and presentation of particulate antigens, such as those associated with Listeria monocytogenes bacteria, yet it is not required for antigen uptake. Mechanistically, we provide evidence that in DCs, Vav GEFs are essential to link ITAM-dependent receptors with the activation of the NOX2 complex and production of reactive oxygen species (ROS), which regulate phagosomal pH and processing of particulate antigens for cross-presentation. Importantly, we show that genetic disruption of the DAP12/FcRgamma-Vav pathway leads to antigen presentation defects that are more profound than in DCs lacking NOX2, suggesting that ITAM signaling also controls cross-presentation in a ROS-independent manner.     

Clinical significance of healthcare-associated infections in community-onset Escherichia coli bacteraemia

BACKGROUND: The increasing antimicrobial resistance of Escherichia coli infection is of great concern, even for community-onset infections. METHODS: We conducted a retrospective cohort study of patients with E. coli bacteraemia who visited the emergency department of the Samsung Medical Center from February 2002 to December 2005 to identify the risk factors for mortality and association between healthcare-associated (HCA) infection and mortality. We classified community-onset E. coli bacteraemia into community-acquired (CA) and HCA infections. RESULTS: A total of 508 patients with E. coli bacteraemia were enrolled (mean age, 61.8 +/- 14.3 years; male/female, 191:317). The HCA E. coli bacteraemia had significantly higher severity of illness and higher antimicrobial resistance rate than CA bacteraemia. The overall 30-day mortality rate was 13.6% (69/508) and the mortality of HCA infections was significantly higher than that of CA infections (26.4% versus 9.6%, P < 0.001). In multivariate analysis, high Charlson's co-morbidity index (OR 4.84, 95% CI 2.14-10.95, P < 0.001), high Pitt bacteraemia score (OR 32.03, 95% CI 13.08-74.43, P < 0.001), presentation with acute renal failure (OR 4.11, 95% CI 1.90-8.89, P < 0.001) and HCA bacteraemia (OR 2.34, 95% CI 1.09-5.01, P = 0.030) were found to be the significant risk factors for 30-day mortality in E. coli bacteraemia. CONCLUSIONS: The mortality rate of HCA E. coli bacteraemia was higher than twice that of CA bacteraemia and HCA bacteraemia was one of the significant risk factors for mortality, even after adjusting for a large number of potential confounders.     

A survey of community-associated methicillin-resistant Staphylococcus aureus in Korea

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA), originally restricted to hospitals, has emerged as a significant pathogen in the community. Although MRSA accounts for over 60% of S. aureus in tertiary hospitals in Korea, little is known about the epidemiology of community-associated MRSA (CA-MRSA). METHODS: From January to July 2005, a hospital laboratory-based survey was conducted in seven community-based or tertiary hospitals. The medical records and Health Insurance Review Agency databases were reviewed and MRSA isolated from patients without apparent risk factors was defined as CA-MRSA. Susceptibilities to 12 antibiotics were tested by the disc diffusion method. SCCmec typing, Panton-Valentine leucocidin (PVL) gene detection and multilocus sequence typing (MLST) were performed according to published protocols. RESULTS: Of 3,251 S. aureus, 1,900 (58.4%) were MRSA. CA-MRSA accounted for 112 (5.9%) of the MRSA. Of the 112 CA-MRSA isolates, 27 and 33 were found to be pathogens and colonizers, respectively. Fifty-two isolates from the patients with chronic otitis media were classified as 'undetermined'. Most of the 27 CA-MRSA patients had skin and soft tissue infections or acute ear infections. None of the patients died during the study period. Among 72 isolates tested, 64% were multidrug-resistant. SCCmec type IVa was the most common type among the colonizers and pathogens. On MLST analysis, ST72 was predominant, but ST5 and ST239 were prevalent in the 'undetermined' group. None possessed the PVL gene. CONCLUSIONS: Despite MRSA-endemic hospital settings, CA-MRSA infections are not common in Korea. A new clone of CA-MRSA, ST72-SCCmec type IVa without the PVL gene, is the most common form.     

俯卧位双钢板内固定材料置入治疗肱骨中下段粉碎性骨折19例

选择2005-01/2007-06中南大学湘雅三医院骨科应用俯卧位双钢板内固定材料置入治疗肱骨中下段骨折患者19例.男12例,女7例;年龄19～65岁,平均35.63岁.左侧10例,右侧9例.单纯骨折13例,合并桡神经挫伤6例.均为闭合性粉碎性骨折.所使用的内固定材料为肱骨金属解剖型接骨板,生产型号为YJQⅠ(重建).平均随访10个月,所有病例均获骨性愈合,平均愈合时间3个月,没有延迟愈合、骨不连及伤口感染等并发症.Aitken和Rorabeek评分:优14例,良3例,可2例,差0例.优良率达到89.47%.     

Ultrasonic signs of pneumothorax: Preliminary work

Ultrasonography is considered to have limited application in respiratory diseases because air reflects sound waves. Twenty-four patients with radiologically confirmed pneumothorax and 100 healthy subjects underwent sonography. In all normal subjects, the hyperechoic pulmonary interface showed respiratory motions termed the “gliding sign” with some comet-tail artifacts. Sonographic signs were shown in all pneumothoraces: disappearance of the gliding sign and no comet tails. The extent of collapse cannot be evaluated, but it is possible to determine its area in partial pneumothorax (N = 5). The follow-up (N = 8) showed the reappearance of the gliding sign. Ultrasonography may be helpful in diagnosing pneumothorax in certain cases. © 1993 John Wiley & Sons, Inc.     

The contralateral effect conferred by intra-articular adenovirus-mediated gene transfer of viral IL-10 is specific to the immunizing antigen

We have demonstrated previously that local, adenoviral-mediated gene transfer of vIL-10 to a single joint of rabbits and mice with experimental arthritis can suppress disease in both the treated and untreated contralateral joints. These therapeutic effects observed in distant untreated joints following local intra-articular gene delivery have been termed the 'contralateral effect'. To begin to understand the underlying immunologic mechanism that confers this effect, a dual-antigen model of antigen-induced arthritis (AIA) in rabbit knee joints was utilized. Rabbits were immunized against two antigens, ovalbumin and keyhole limpet hemocyanin, and AIA generated by intra-articular injection of each antigen into contralateral knees. Intra-articular adenovirus-mediated gene transfer of vIL-10 significantly reduced intra-articular leukocytosis and cartilage matrix degradation, while preserving near normal levels of cartilage matrix synthesis within treated joints. However, no antiarthritic effect was conferred in the contralateral control joints that received only a marker gene, in contrast to the results seen in a single-antigen AIA model. These results suggest that the distant antiarthritic effects associated with local gene delivery to joints are antigen-specific, and not due to vIL-10-induced generalized immunosuppression of the animal.     

50例尿道会师牵引术病人的护理

[目的]探讨临床护理在减少尿道会师牵引术并发症中的作用。[方法]回顾性分析50例尿道会师牵引术病人的护理,并与外院相同病人的并发症发生率做对比。[结果]50例病人中,10例发生尿道狭窄,行定期尿道扩张术,随诊1年排尿正常;2例发生暂时性尿失禁;3例发生阳痿,6个月后恢复;其余35例无并发症发生。[结论]加强尿道会师牵引术病人的护理有助于降低手术并发症的发生。     

Protein tyrosine phosphatase conjugated with a novel transdermal delivery peptide,astrotactin 1–derived peptide recombinant protein tyrosine phosphatase (AP-rPTP), alleviates both atopic dermatitis–like and psoriasis-like dermatitis

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