T辅助细胞在疫苗研制中的作用

发展感染性疾病疫苗之关键挑战在于利用确定的抗原以刺激产生能引起保护作用的合适的免疫反应。肽类疫苗的运用得到了极大的关注，其意义在于，已知不同的多表位构成单一结构以诱导出所希望的免疫反应所表现出的灵活性。这一般比利用减毒的活疫苗要安全并且相对而言比制造亚单位疫苗要容易。然而，多肽疫苗的发展面临巨大挑战。这一方法在诱导遗传背景复杂的人群免疫反应方面受到限制，这与主要组织相溶性复合物(MHC)多态性有关。因同样的理由，肽类免疫应答常因缺乏适当的辅助T淋巴细胞(HIL)而引导出不充分的细胞毒素T淋巴细胞(CTL)和抗体反应。另一个运用线性肽链结构的可能缺点是：为了引导出合适抗体反应，表面免疫球蛋白受体簇对于激活静息的B细胞就成为必须因素。由WHC多肽性引起的问题可由运用不加区别的T细胞表位来解决。从麻疹病毒F蛋白(氨基酸288到302)中得到的不加区别的T细胞表位和鼠的确定结合在多种MHC分子上的辅助T细胞表位(v1EB，aa191-209)已被定性并且被用于能极大激发免疫应答的结构中，以克服单一限制型免疫应答的缺陷。合成的，非自然Pan DR表位(PADRE)具有退化的结合几种通常HLA—DR的能力，能以绝对效价和抗体反应质量两种形式来增强激发短肽链的免疫应答。另外，一些所谓的从流感病毒血凝素(HA)来的“不加区别的”T细胞表位，恶性疟疟原虫红细胞前期抗原和分枝杆菌蛋白被报道能激发广泛的免疫应答。为了不加区别地结合于几种同型和同种异型的MHCⅡ类分子，这些肽类应显示出部重叠MHC结合形式或应利用保存于配体中的固定位点和应缺失等位基因特异性固定残基，以防止结合于其它Ⅱ类分子。了解MHCⅡ类分子对肽链的不加区别及特异性识别的生物物理学基础将为在疫苗设计中突破遗传限制的策略提供分子水平的依据。     

Acute pancreatitis combined with acute Budd-Chiari syndrome as the initial manifestation of small cell lung cancer.

Tumor metastasis to the pancreas is a rare but recognized cause of acute pancreatitis. Autopsy series have reported a 24-40% of pancreatic involvement in small cell lung cancer. However, only a very few cases of tumor-induced acute pancreatitis have been described. Budd-Chiari syndrome complicating lung cancer is a rarely reported condition. We report a 68-year-old woman with extensive small cell lung cancer with the unusual initial presentation of both acute pancreatitis and acute Budd-Chiari syndrome. This patient suffered from progressive epigastralgia for 3 weeks. Severe epigastralgia with radiation to back and progressive jaundice developed 2 days prior to admission. After admission, the liver enlarged rapidly and the ascites increased markedly. Chest roentgenogram showed a mass lesion over the left lower lung field. Poorly differentiated carcinoma cells were found in ascites and bone marrow. The patient died on the ninth day of hospitalization before chemotherapy was initiated. Prompt diagnosis of extensive-stage small cell lung cancer may allow early chemotherapy treatment which favorably influences recovery when the pancreatitis is mild. Although prolonged survival might have been expected had this patient recovered from pancreatitis and received chemotherapy, diagnosis was delayed due to difficulty in immunohistochemical diagnosis of the tumor and the unusual clinical presentation. The use of stains employing antibodies against neurofilament and neuron-specific enolase cell antigens is important for early diagnosis of poorly differentiated metastatic tumor cells.     

Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma.

The present study aimed to determine the alterations of antioxidant activities in erythrocytes from patients with nonsmall cell lung carcinoma (NSCLC). A comparative study of the systemic antioxidant activities in red blood cell lysate from subjects with NSCLC and healthy control subjects was conducted. The antioxidants catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured using chemical kinetic reactions under spectrophotometry. In total, 189 cases of mostly advanced-stage IIIB or stage IV NSCLC and 202 healthy controls were studied. In subjects with lung cancer, there was similar catalase activity, lower SOD activity (median (interquartile range) 13.4 (9.0-27.2) versus 48.7 (27.0-64.3) U x (ghaemoglobulin(Hb)(-1)), and higher GPx activity (175.2 (126.6-288.3) versus 49.2 (39.5-59.2) mU x (gHb)(-1)) compared with controls. The antioxidant activities in lung cancer subjects were not associated with age, sex, smoking status, or tumour cell types. However, more advanced disease (stage IV compared with stage IIIB) was associated with lower SOD activity. Using multivariable analysis, the presence of lung cancer independently predicted SOD and GPx activities. In conclusion, nonsmall cell lung carcinoma in Chinese subjects is associated with alterations in systemic antioxidant activities, which may play an important role in carcinogenesis.     

Pleuroperitoneal shunt for recurrent malignant pleural effusions.

The therapeutic options available for the management of malignant pleural effusions associated with a restricting malignant cortex remain unsatisfactory. The efficacy of pleuroperitoneal shunts was evaluated in 16 patients with recurrent malignant effusions. There were no operative deaths; one patient died on the third postoperative day as a result of lymphangitis carcinomatosa. The median hospital stay was five (range 3-21) days. Palliation was obtained in all but one of the other 15 patients. There was no appreciable reaccumulation of pleural fluid as judged by radiography. Two patients developed occlusion of the shunt. In one case this was due to blood clots in the pleural catheter and necessitated insertion of a new shunt. The other shunt was removed because of obstructing infected fibrin debris, and a rib resection was performed. There were eight deaths related to the underlying malignancy after a mean interval of 7.3 (range 1.5-23) months. The other six patients are still alive, with a mean survival of 11.0 (range 5-20) months, and have achieved good symptomatic relief. The insertion of a pleuroperitoneal shunt can offer effective palliation for patients with recurrent malignant pleural effusions.     

Severe hypokalemia in thyrotoxic periodic paralysis

Thyrotoxic hypokalemic periodic paralysis is an uncommon but sometimes fatal disease in which early recognition and therapy may prevent untoward complications. The case of a 26-year-old Chinese man who presented to the emergency department with rapidly progressive profound weakness and severe hypokalemia (serum potassium, 1.2 mEq/L) is presented. The patient required endotracheal intubation, ventilatory assistance, and intravenous potassium administration. Emergency medical evaluation and management of this entity are discussed.     

Serological diagnosis of infection by Shigella dysenteriae-1 in patients with bacillary dysentery

A total of 192 samples of serum from 113 Sri Lankan patients with clinical dysentery was examined for antibodies of the IgM class to the lipopolysaccharides (LPSs) of Shigella dysenteriae-1 and Escherichia coli O157:H7. By means of ELISA and immunoblotting, 59 patients were found to have serum antibodies to the LPS of S. dysenteriae-1 only. Four samples from one patient were found to contain serum antibodies to the LPSs of both S. dysenteriae-1 and E. coli 0157: H7. Antibodies to the LPS of S. dysenteriae-1 were also detected in 16 samples from 25 children, from Sri Lanka, with no previous history of dysentery; one of these children also had antibodies to the LPS of E. coli 0157: H7. Analysis of 16 samples from apparently healthy children in the U.K. showed that only one serum contained antibodies to the LPS of S. dysenteriae-1. This patient had a history of recent travel to Pakistan. The isolation of S. dysenteriae-1 remains the preferred test for the diagnosis of bacillary dysentery. The use of serology as a means of providing evidence of infection with S. dysenteriae-1, however may prove to be a useful adjunct to cultural techniques but needs to be validated in an area where this organism is endemic.     

Diffraction tomography by a method of image projections

A method of three-dimensional diffraction tomography based on image projections is derived. Inversion methods based on projections generally are inaccurate due to the spreading nature of the scattered wave. By backpropagating the field onto a single plane in the image region, diffraction effects are reduced and a projection of the weakly scattering object is generated. Consequently, conventional X-ray inversion techniques may be used to image the object. The relationship between the backpropagated field and the projection is derived both for high frequency incident waves and low spatial frequency scatterers. The generalized image kernel allows the use of curved or misaligned recording surfaces. Numerical results are included.