Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

Multi-parameter prediction of HLA class Ⅰ restricted cytotoxic T lymphocyte epitopes for human proliferating cell nuclear antigen

Objective To predict the HLA class Ⅰ restricted cytotoxic T lymphocyte epitopes for human proliferating cell nuclear antigen (PCNA). Methods By using 3 epitope prediction databases which including MHC binder ( BIMAS and SYFPEITHI databases) and proteasome cutting site ( PAProC databases), the epitopes of PCNA were predicted by analyzing several parameters and methods. Results After comprehensive analysis,we have obtained two possible HLA-A0201 restricted CTL epitopes SMSAD-VPLV (228-236, score 447 633. 595 ) and LINEACWDI ( 22-28, score 127 966.779);two HLA-A24 re-stricted CTL epitopos DYEMKLMDL ( 113-121, score 563 994.9 ) and EFARICRDL ( 143-151, score 40 540.7);two HLA-A1101 restricted CTL epitopes LTSMSKILK (72-80, score 1334. 2680 ) and DVPLV-VEYK (232-240,score 736.9236). Conclusion The multi-parameter epitope prediction method is feasi-ble for cytotoxic T lymphocyte epitope prediction.     

缬沙坦加参麦注射液治疗充血性心力衰竭的临床观察

目的观察缬沙坦（Valsartan）加参麦注射液（Shenmai Injection,SI）对充血性心力衰竭（CHF）心肌损害的疗效。方法采用随机分组的方法,分别用常规治疗（31例）和缬沙坦、SI加常规治疗（31例）,并对CHF的各项实验室指标[血浆肌钙蛋白T（cTnT）、心肌酶谱]进行观察。结果在CHF进程中,cTnT浓度随着心功能恶化呈进行性增高。应用缬沙坦加SI治疗2周后,患者左室收缩功能得到明显改善,未发现严重不良反应。结论血浆cTnT可作为CHF患者预后判断的一项重要生化指标。缬沙坦加SI是治疗CHF安全有效的药物。     

影响终末期肾衰竭患者心脏扩大的因素

目的了解成都铁路分局医院血液进化中心终末期肾衰竭并维持性血液透析患者心脏扩大的影响因素,以便提高患者的血液透析质量和生存率。方法回顾本血液净化中心收治的216例终末期肾衰竭并维持性血液透析2月以上患者,根据心脏彩色多普勒检查,分为心脏扩大与心脏未扩大2组,对可能影响心脏扩大的因素:年龄、血液透析病程、每周血液透析时间、高血压、容量超负荷、血红蛋白水平、低蛋白血症等用SPSS10.0软件作Logistic回归分析。结果终末期肾衰竭并维持性血液透析患者216例,心脏扩大者183例,未扩大者33例,心脏扩大的发生率为84.72%。心脏扩大与容量超负荷呈显著正相关,P=0.002,OR值42.619;心脏扩大与高血压呈正相关,P=0.026,OR值15.353;心脏扩大与血红蛋白水平呈负相关,P=0.043,OR值0.934。心脏扩大与年龄、血液透析病程、每周血液透析时间和低蛋白血症无相关关系。结论终未期肾衰竭并维持性血液透析患者心脏扩大发生率高,而容量超负荷、高血压、血红蛋白水平是影响它的关键,高血压及容量超负荷是促进心脏扩大的独立危险因素,血红蛋白水平下降亦是促进心脏扩大的独立危险因素。     

Myocardial perfusion SPECT reconstruction: Receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.     

升主动脉成形术中期效果分析

Objective Reduction ascending aortoplasty is an alternative procdure to the replacement of the ascending aorts in case of ascending aorta dilation. However,its applicabikity is still under debate.This retrospective study was designed to evaluuate the midterm follow-up of unsupported ascending reduction aortoplasty for of the ascending aorta in petients with aortic valve dis- ease.Methods From October ,1996 to April,2007, a total of 54 patients with aortic valve disease and dilatation of the ascending aorta underwent unsupported reduction aortoplasty in combination with aortic valve replacement at our institution The diameter of the ascending aorta was measyred before and early after sugery and then later between 13 and 96 menths [mean (23 ±16)months] posto- perativeiy using echocardiography.Results Two patients were dead with thean overall perioperative mortality rate was of 3.7%. The reduction aortoplasty decreased the diameter of the aorta from (45.77±6.02) mm p～eope～afive]y to (34.67 ～4.81) mm early after surgery (P<0.01). During follow-up, the diameter d aorta increased from (34.67±4.81) mm early after surgery to (37.65± 6.35) mm after a mean follow-up of (23±16) months (P<0.01), including the diameters are greater than > 45 mm within 5 pa- tients. Aortic stenosis and an early postoperative diameter greater than 40 mm m'e independent risk factors for redilatation. Conchusion Because of the unsatisfied midterm follow-up redilation of unsupported reduction aortoplasty for dilation of the ascending aorta with aortic valve disease, this group of patients needs continued intimate fallow-up or even reoperation. The patients of stenosis is the surtable indication for RAA, and it is necessary to reduce the diameter of aorta to be lees than 40 mm to prevent redilation.     

Fluctuating PEEP (F–PEEP) versus conventional PEEP in dogs with asymmetrical lung injury

Fluctuating PEEP (F-PEEP) is a newly developed PEEP in which end-expiratory pressure (EEP) is periodically changed within a certain range. In a dog model with unilateral lung injury induced by the introduction of hydrochloric acid, F-PEEP in which the EEP was periodically changed from 0.5 to 1.5 kPa at periods of 6 min, and conventional PEEP (C-PEEP) with an optimized EEP of 1.0 kPa, were each applied for 30 min. F-PEEP produced a significantly greater improvement of PaO2 and intrapulmonary shunt (QS/QT) than C-PEEP, and at the low EEP phase, the greatest improvement accompanied by an increased dynamic compliance and a large cardiac output was obtained. These results suggest that F-PEEP provides a useful mode of artificial ventilation for the treatment of unilateral lung injury.     

Analysis of reflex activity in cardiac sympathetic nerve induced by myelinated phrenic nerve afferents

Electrical stimulation of the phrenic nerve afferents evoked excitatory responses in the right inferior cardiac sympathetic nerve in chloralose-anaesthetized cats. The reflex was recorded in intact and spinal cats. The latency and threshold of the volley recorded from the phrenic nerve as well as of the cord dorsum potentials evoked by electrical stimulation of the phrenic nerve indicated that group III afferents were responsible for this reflex. The phrenicocardiac sympathetic reflex recorded in intact cats was followed by a silent period. The maximum amplitude of the reflex discharges was 800 microV, the latency was 83 ms and the central transmission time 53 ms. Duration of the silent period lasted up to 0.83 s. In spinal cats the reflex was recorded 5.5-8 h after spinalization. The maximum amplitude of the spinal reflex discharges ranged from 22 to 91 microV and the latency from 36 to 66 ms.     

神经肽Y对免疫细胞活性的影响

神经肽Y（NPY）是广泛分布于中枢神经系统和外周神经各部位的神经肽类物质。本实验观察NPY在体外对几种免疫细胞活性的直接作用。结果表明，NPY对小鼠T淋巴细胞丝裂原反应性和NK细胞的杀伤活性均无明显影响（P＞0．05），对巨噬细胞分泌溶菌酶有明显抑制作用（P＜0．05）；而对B淋巴细胞丝裂原反应性则有明显的促进作用（P＜0．05）。上述结果提示，NPY对部分免疫细胞功能的影响因细胞种类而异。