Major Histocompatibility Complex Class I Viral Antigen Processing in the Secretory Pathway Defined by the trans-Golgi Network Protease Furin

Classical antigen presentation by major histocompatibility complex class I molecules involves cytosolic processing of endogenously synthesized antigens by proteasomes and translocation of processed peptides into the endoplasmic reticulum (ER) by transporters associated with antigen presentation (TAP). Alternative pathways for processing of endogenous antigens, generally involving the ER, have been suggested but not fully proved. We analyzed the potential for class I presentation of proteolytic maturation of secretory antigens in the exocytic pathway. We found that hepatitis B (HB) virus secretory core protein HBe can efficiently deliver COOH-terminally located antigenic peptides for endogenous class I loading in the absence of TAP. Antigen presentation to specific cytotoxic T lymphocytes correlates with protein maturation at the COOH terminus, since modification of maturation and transport of HBe through the secretory pathway alters antigen presentation. Both maturation and a necessary processing step occur in the Golgi or post-Golgi compartment. Antigen presentation is independent of proteasome activity, but inhibitors of the trans-Golgi network resident protease furin inhibit both HBe maturation and antigen presentation. These results define a new antigen processing pathway located in the secretory route, with a central role for proteolytic maturation mediated by the subtilisin protease family member furin as an efficient source for antigen presentation.     

Psoas abscess

A psoas abscess is infrequently diagnosed on initial presentation. This report reviews the presentation of a patient with a complicated psoas abscess. The pathophysiology and the clinical and laboratory presentation of patients with this disease entity are reviewed.     

Circadian patterns of emergency asthma presentations: implications for staffing and treatment

Are there circadian patterns for time of presentation and clinical status in asthmatic patients admitted to an emergency department for acute exacerbations? DESIGN: Prospective observational study. SETTING: Urban community teaching hospital emergency department. PARTICIPANTS: 279 consecutive patients who presented a total of 310 times with asthma exacerbations between October 19 and December 31, 1993. We grouped patients aged 16 years and above as adults and patients younger than 16 years of age as children. INFORMATION COLLECTED: Time of emergency department presentation, time attack began (for adult patients), peak expiratory flowrate prior to emergency department treatment (for adult patients), need for hospital admission, ventilatory failure during an acute attack, and death during an acute attack. RESULTS: Circadian patterns were demonstrated for time of presentation. For the total study group, the peak time of presentation was 8:00 PM to 11:59 PM (p < 0.05) and the trough time of presentation was 4:00 AM to 7:59 AM (p < 0.01). There were differences in peak time of presentation for patients grouped by age. For adult patients only, the peak time of presentation was 8:00 AM to 11:59 AM (p < 0.01), whereas for children only, the peak time of presentation was 8:00 PM to 11:59 PM (p < 0.001). No statistically significant patterns in time of attack onset, hospital admission rates, or peak flow measurements were observed. CONCLUSIONS: There are circadian patterns for the time at which patients with acute asthmatic exacerbations present to our emergency department. Adult patients have a peak time of presentation between 8:00 AM and 11:59 AM, whereas children have an apparent peak time of presentation between 8:00 PM and 11:59 PM. For all age groups, there is a trough in presentation between 4:00 AM and 7:59 AM.     

手法处理头位难产在少数民族偏远地区的意义

目的 探讨经阴道徒手旋转胎头处理头位难产的临床应用价值.方法 回顾性分析经阴道徒手旋转胎头处理头位难产的病例,分析其异常头先露、先露高低、宫口扩张及胎儿体重与徒手旋转胎头处理后分娩情况.结果 头位难产1356例,占分娩总数的20.56%.对其中1030例孕妇进行了经阴道徒手旋转纠正头先露异常,顺产842例,成功率81.75%;剖宫产141例(13.69%),阴道助产47例(4.56%),失败188例,失败率18.52%.持续性枕后位与枕横位徒手旋转胎头成功率明显高于前不均倾位及高直位(P<0.01);先露S+1以下徒手旋转胎头成功率明显高于S+1以上者(P<0.01);宫口开大4cm以上徒手旋转胎头成功率明显高于宫口开大4cm以下者(P<0.01);胎儿体重3750g以下时,徒手旋转胎头成功率明显高于胎儿体重3750g以上者(P<0.01).结论 重视头盆评分及产程观察,适时经阴道徒手旋转异常头先露,能有效提高头位难产的阴道分娩率,降低剖宫产率,对少数民族偏远地区有重要意义.     

An endogenous processing pathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class II-restricted T cells

The recognition of virus-infected cells by class I MHC-restricted cytotoxic T cells requires endogenous processing of antigen for presentation. It is still unclear whether endogenous processing of antigen can be utilized by class II MHC molecules for presentation. To test this possibility, a human B cell line expressing HLA-A2 and HLA-DR1 was infected with a recombinant vaccinia virus expressing the Influenza A virus M1 matrix protein (VAC-M1) and was assayed for lysis by different M1-specific cytolytic T cell lines, restricted by either HLA-A2 or by HLA-DR1. Class II-restricted lysis of VAC-M1-infected cells did occur. This lysis required de novo M1 synthesis and was not due to exogenous antigen. Several properties of the endogenous processing pathway for class II-restricted presentation were different from those of the pathway utilized by class I molecules. First, class II-mediated recognition of VAC-M1 infected cells was less efficient, requiring higher doses of virus and longer infection times, than the class I-mediated recognition. Second, chloroquine completely blocked presentation of endogenous M1 to class II-restricted T cells but had no effect on the class I-restricted presentation. Third, the class II-restricted presentation of M1 was only mildly affected by Brefeldin A, a drug that prevents transport from the endoplasmic reticulum to the Golgi, whereas the class I-restricted presentation of M1 was completely abrogated by this drug. These data demonstrate the existence of an endogenous processing pathway for the presentation of cytosolic antigen by class II molecules and show that this pathway is distinct from the one used for presentation by class I molecules.     

Adeno-associated virus capsid antigen presentation is dependent on endosomal escape

Adeno-associated virus (AAV) vectors are attractive for gene delivery-based therapeutics, but data from recent clinical trials have indicated that AAV capsids induce a cytotoxic T lymphocyte (CTL) response that eliminates transduced cells. In this study, we used traditional pharmacological agents and AAV mutants to elucidate the pathway of capsid cross-presentation in AAV-permissive cells. Endosomal acidification inhibitors blocked AAV2 antigen presentation by over 90%, while proteasome inhibitors completely abrogated antigen presentation. Using mutant viruses that are defective for nuclear entry, we observed a 90% decrease in capsid antigen presentation. Different antigen presentation efficiencies were achieved by selectively mutating virion nuclear localization signals. Low antigen presentation was demonstrated with basic region 1 (BR1) mutants, despite relatively high transduction efficiency, whereas there was no difference in antigen presentation between BR2 and BR3 mutants defective for transduction, as compared with wild-type AAV2. These results suggest that effective AAV2 capsid antigen presentation is dependent on AAV virion escape from the endosome/lysosome for antigen degradation by proteasomes, but is independent of nuclear uncoating. These results should facilitate the design of effective strategies to evade capsid-specific CTL-mediated elimination of AAV-transduced target cells in future clinical trials.     

An investigation of factors that determine when men with erectile disorder present for treatment

This study by Sangan Sookdeb explored the factors that determine the time interval between men suffering the onset of erectile disorder and their presentation for treatment. As prognosis is considered to be related negatively to the length of time a man suffers erectile disorder understanding factors that delay presentation may identify changes in practice methods that will encourage earlier presentation.     

The effectiveness of palliative care education delivered by videoconferencing compared with face-to-face delivery

As part of a four-year study into the use of videoconferencing in palliative care, the delivery of workshops on palliative care to community nurses was evaluated by the Open University. Twenty nurses were randomly allocated to alternating videoconferencing and face-to-face modes of presentation. The quantitative study measured the amount of learning that occurred in each workshop with pre-tests and post-tests, and the mode of presentation. Forty-nine workshop attendances were analysed. The qualitative study used observation and analysis of videorecordings to assess the activity and attention spans in interactive communication during workshops, while a combination of interviews and questionnaires was used to assess the participants' level of satisfaction with presentation. The results showed that the nurses' level of satisfaction with the instructional presentation was high in both modes of presentation. Despite difficulties at the start of the project in the videoconferencing presentation, there was little difference between the modes of presentation in achievement scores or the gain in achievement scores. Although the learners preferred face-to-face workshops, they learnt as much from a videoconferenced workshop. Videoconferencing was less suitable for psychological or emotional discussions, but this may have been due to the time constraints on the workshops. Some features of videoconferencing suggest it could be used effectively in helping learners discuss sensitive issues. The Current Learning in Palliative Care (CLiP) worksheets were found to be an effective means of delivering learning.     

Child health education for the foreign-born parent

Providing child health education for the foreign-born parent presents unique concerns related to language and culture. An innovative approach in a transcultural format used a presentation of basic child health information in English, with translators as facilitators. Foreign-born parents who need partial or complete language interpretation have ready access to translation support. The parents offer questions, comments, suggestions and evaluate the presentation through the translator. Each presentation can accommodate more than one language, since participants are grouped with the appropriate translator. The presentation is done in English and paced to allow for translation to be completed as material is offered. This type of presentation allows discussion of child health in a forum apart from the pediatric care setting. Because the presentation is the only focus, parents do not have the additional concern of immediate care of the child added to communication issues. Vocabulary relative to health care is developed from English into the parents' primary language, with the support of the translator. The pediatric nurse presenter has an opportunity to review health care practices that parents prefer, as well as interpret safety and efficacy.     

Effect of Delay in Hospital Presentation on Clinical and Imaging Findings in Acute Pulmonary Thromboembolism

Background

There is limited information on the extent and clinical importance of the delay in hospital presentation of acute pulmonary thromboembolism (PTE).

Objective

The aim of this study was to investigate the delay in hospital presentation of PTE and its association with clinical and imaging findings in PTE.

Methods

This prospective study was conducted on patients admitted to our hospital with a diagnosis of acute PTE between September 2007 and September 2011. Relationships between delay in hospital presentation and clinical findings, risk factors, imaging findings, and in-hospital mortality were analyzed.

Results

Of the 195 patients enrolled, 84 (43.1%) patients presented 3 days after the onset of symptoms. Patients with chest pain, history of immobility for more than 3 days, recent surgery, and estrogen use had significantly less delayed presentation. Right ventricular dysfunction was significantly more frequent in patients with delayed presentation (odds ratio [OR] = 2.38; 95% confidence interval [CI] 1.27−4.44; p = 0.006); however, no relationship was found between delay in presentation and pulmonary computed tomographic angiography or color Doppler sonography findings. Patients with delayed presentation were at higher risk of in-hospital mortality (OR = 4.32; 95% CI 1.12−16.49; p = 0.021).

Conclusions

Our study showed that a significant portion of patients with acute PTE had delayed presentation. Also, patients with delayed presentation had worse echocardiographic findings and higher in-hospital mortality.     

经阴道彩色多普勒超声诊断早期异位妊娠的研究

目的 评价经阴道彩色多普勒超声诊断早期异位妊娠的作用.方法 回顾性分析26例宫内妊娠、22例异位妊娠患者经阴道彩色多普勒超声诊断仪测量子宫内膜厚度、比较螺旋动脉显示率.结果 宫内妊娠组子宫内膜厚度比异位妊娠组厚,有显著性差异(P<0.05).宫内妊娠组中,18例子宫内膜内显示螺旋动脉,显示率为69%;22例异位妊娠患者中,1例内膜中有螺旋动脉血流信号显示,显示率为4.5%;两组螺旋动脉显示率差异有统计学意义(P<0.05).结论 经阴道彩色多普勒超声检测早期妊娠期间子宫内膜厚度、螺旋动脉显示率可明显提高异位妊娠的诊断率;可为异位妊娠的诊断提供更多的临床信息.     

Measurement of nuchal skin fold thickness in the second trimester: influence of imaging angle and fetal presentation.

OBJECTIVE: To assess the effect of imaging angle and fetal presentation on the measurement of nuchal skin fold thickness (NFT) in the second trimester. METHODS: Fetal NFT was prospectively measured in 921 women at 18-21 weeks' gestation. The population was divided into two groups according to fetal presentation. Group A comprised 643 fetuses in cephalic or transverse presentation and Group B comprised 278 fetuses in breech presentation. To determine whether there was a difference in NFT depending on imaging angle, in Group A the NFT was measured on the standard axial horizontal images and then on images obtained after moving the transducer about 30 degrees toward the occiput. In Group B an assessment was made as to whether NFT changed with fetal presentation. Initial measurements were made with the fetuses in breech presentation. Repeat NFT measurements were made after 15 min in 64 fetuses that had converted to cephalic or transverse presentation. Statistical analysis was performed using a paired t-test. RESULTS: The mean NFT on the standard horizontal image was 5.2 mm, while that on the 30 degrees occiput image was 4.0 mm. The difference was significant (P < 0.001). One hundred and twenty-three (19.1%) fetuses had a NFT greater than 6 mm on the standard image, but only two (0.3%) had an NFT of > 6 mm on the 30 degrees occiput image. There were no chromosomal or structural abnormalities in the 123 fetuses in which the NFT was > 6 mm. The mean NFT of 64 fetuses in the breech presentation was 4.4 mm, while it was 3.9 mm when they had converted to other presentations. The difference was statistically significant (P = 0.001). In breech presentation, 13/64 (20.3%) fetuses had a NFT greater than 6 mm compared to only one (1.6%) fetus in the other presentations. There were no structural or chromosomal abnormalities in any fetus with a NFT > 6 mm in either group. CONCLUSIONS: In this study the NFT measurement varied with scan direction and fetal presentation. To avoid falsely thickened NFT measurements the scan should be directed to image the posterior surface of the occipital bone. This can be achieved by scanning from a 30 degrees occipital direction. Also, NFT is greater in fetuses in a breech presentation. Attention to these details can reduce false-positive NFT measurements.     

以皮肤病变为首发表现的糖尿病误诊分析

目的 探讨以皮肤病变为首发表现的糖尿病的临床特点。以期能为早期诊断糖尿病提供线索。方法 总结分析以皮肤病变为首发表现的13例糖尿病的临床资料。结果 所有病例首疹就诊均误诊，主要是对糖尿病的皮肤病变缺乏认识，对无糖尿病典型表现的患忽视了检查血糖。结论 临床上糖尿病的皮肤病变较常见。对有反复真菌感染，化脓性皮肤病，顽固性皮肤瘙痒的中老年人，应重视血糖测定。避免误诊糖尿病。     

Delayed presentation for human immunodeficiency virus (HIV) care among veterans: a problem of access or screening?

BACKGROUND: Despite the effectiveness of antiretroviral therapy, nearly half of patients entering human immunodeficiency virus (HIV) care have advanced disease. Many attribute this delay to poor access to healthcare. Others argue that delays will persist until routine screening is adopted. The Veterans Health Administration (VA) is a unique laboratory to examine whether access to comprehensive health benefits results in earlier entry into HIV care. METHODS: Retrospective observational study of 4368 HIV-positive patients entering HIV care during 1998-2002 at VA medical centers nationwide. Outcomes of interest: rates of acquired immune deficiency syndrome in year of presentation; duration of VA utilization before HIV presentation; presence of "clinical triggers," signaling greater risk of HIV infection, before presentation. RESULTS: Fifty-one percent (n = 2211) of all patients presented with CD4 counts of < 200 cells/mm. Thirty-nine percent (n = 1697) of all patients used other VA services before presentation for HIV care, with median duration of 3.6 years (interquartile range 25-75: 2.2-5.1 year) and 6 physician visits [interquartile range (IQR), 25-75: 2-18 visits] between first utilization and HIV presentation. No difference existed in the percentage presenting with CD4 counts <200 cells/mm among those with and without prior VA healthcare (50% vs. 51%, P = 0.76). Only 13% of those with prior VA healthcare demonstrated a clinical trigger before HIV presentation. CONCLUSIONS: More than half of veterans entered HIV care with an acquired immune deficiency syndrome diagnosis at presentation irrespective of whether they had previously established healthcare in the VA. Access to care does not seem to be the primary cause of delayed HIV presentation. Widespread HIV screening is needed to improve rates of early detection.     

脉象波强与瞬时加速度波强(W_1)的相关性研究及其意义

目的分析桡动脉脉象波强与颈动脉瞬时加速度波强(W1)的相关性,探讨其物理学定义及生理学上的意义。方法纳入53例正常人,应用ALOKA Prosoundα10彩色多普勒超声诊断仪进行W1和桡动脉血流加速度测定,应用DDMX-100脉象仪进行桡动脉压力波曲线测定,脉象波强为桡动脉压力上升平均速率与桡动脉血流平均加速度的乘积,研究桡动脉脉象波强与颈动脉瞬时加速度波强的相关性。结果 W1与h1、△P、△U和WI(P)均呈正相关(P0.01)。结论脉象波强具有明确的物理学定义和潜在的临床应用价值,可以作为脉象研究的新方法之一。     

Complementary role of CD4+ T cells and secondary lymphoid tissues for cross-presentation of tumor antigen to CD8+ T cells

MHC class I-restricted tumor antigens can be presented to CD8+ T cells by two distinct pathways: via direct and indirect presentation. The relative contribution of these two pathways toward the initial activation of tumor antigen-specific CD8+ T cells and their subsequent tumor rejection is still vigorously debated. Using a tumor model able to dissect the relative contributions of direct and indirect presentation, we show unequivocally the inefficiency of direct presentation and the essential requirement of indirect presentation for the priming of naive tumor antigen-specific T cells leading to tumor rejection. Moreover, we characterize the essential environment under which indirect presentation occurs, and find efficient cross-priming of tumor-specific CD8+ T cells in the complete absence of secondary lymphoid tissues. The independence of this process from local lymph nodes is compromised, however, in the absence of CD4+ T cell help. Therefore, our paper demonstrates that effective immune protection against tumors requires the cross-priming of CD8+ T cells under conditions that require either CD4+ T cell help, or draining lymph nodes.     

Efficient Communication: Assessment-oriented Oral Case Presentation

OBJECTIVE: To introduce and assess the time savings from and effectiveness of assessment-oriented (AO) oral case presentation as a model of interphysician communication. METHODS: This was a prospective, interventional study of all 10 on-site faculty and 36 residents in a postgraduate year 1 to 3 format emergency medicine residency training program. Residents were requested to perform all oral case presentations in either the traditional or AO formats. Presentations were timed, and residents and faculty rated essential measures of oral case presentation effectiveness: data content, expression of decision making, organization, and overall satisfaction. RESULTS: A total of 199 oral case presentations were sampled-112 traditional and 87 AO. Mean length of presentation for traditional presentations was 117 seconds versus 71 seconds for AO presentations (p < 0.001), a clinically significant difference, without significant differences in the essential measures of case presentation effectiveness. CONCLUSIONS: AO oral case presentation may provide a means for emergency medicine residents to "get to the point" and to communicate effectively and efficiently.