利用独特型——抗独特型理论检测Graves病患者血清中异常免疫球蛋白

根据体外放射分析的原理及独特型——抗独特型理论,利用抗TSH抗体作为结合剂,放射性碘标记的金黄色葡萄球菌A蛋白(~(125)I-SPA)作为定量的示踪剂,建立一种新的检测 Graves病(GD)患者血清中的异常免疫球蛋白(aIgG)的方法,进行了有关方法学的初步研究,探索了TSHAb与aIgG反应的最适反应条件,并与以神经节苷脂为结合剂的酶联免疫吸附分析法(ELISA)作了比较.探讨了aIgG与甲状腺刺激性免疫球蛋白(TSI)的关系.结果显示:TSHAb与GD患者血清中aIgG在体外能够发生特异性结合,而与正常人血清中的IgG、系统性红班狼疮(SLE)患者IgG及糖尿病(DM)患者IgG不发生结合反应.在以aIgG指数作为评价指标时,29名正常人血清aIgG指数为1.06±0.17,其正常范围上限为1.39,在以大于1.39作为阳性时,72名不同临床时期GD患者,初发组阳性率为83%(n=24),临床缓解组阳性率为12%(n=25),复发组阳性率为82%(n=23).正常人血清aIgG指数值与GD初发患者及GD复发患者相比,差异具有极显著性(P<0.001).我们认为本法能较好检出该类aIgG,可用于反映GD患者免疫状况,鉴别诊断及预测治疗缓解后复发的有用指标.     

Immunological distribution of one form of insulin-like growth factor (IGF)-binding protein and IGF peptides in human fetal tissues

Insulin-like growth factors (IGFs) are expressed by, and are biologically active on, human fetal cells. The mitogenic actions of IGF-I are modulated by the 21-41 kDa class of IGF-binding proteins (IGF-BPs). Using a rabbit anti-human IGF-BP antibody raised against a highly pure 26 kDa IGF-BP derived from amniotic fluid, we have compared the cellular location of IGF-BP and IGF peptides in tissue sections from prostaglandin-induced human abortuses of 14-16 weeks of gestation. The monoclonal and polyclonal antibodies used were raised against human IGF-I, but did not distinguish between IGF-I and IGF-II. Positive staining for IGF-BP was seen in every tissue except brain, spleen and thyroid. With the exception of skin, the cellular distribution of IGF-BP was similar to that of IGF peptides. Strong immunostaining was found in hepatocytes, hepatic erythropoietic cells, pulmonary epithelium, the tubular epithelium of kidney, intestinal epithelia, the fetal adrenal cortex and cardiac and skeletal muscle fibres. In skin, IGF-BP was located throughout the dermis and in the germinal layer of the epidermis. IGF peptide in skin was restricted to the deeper dermal layers. In the tibial epiphyseal growth plate both IGF-BP and IGF peptide were located in chondrocytes throughout the proliferation and hypertrophic zones. The similarity in distribution of IGF-BP and IGF peptides in fetal tissues suggests that the latter may exist predominantly complexed to IGF-BP in or on the surfaces of cells in vivo. The distribution of IGF-BP may define the sites of biological action of IGF peptides.     

Haemostatic disturbances in patients bitten by Russell''s viper (Vipera russelli siamensis) in Burma

Patients who are severely envenomed by Russell's viper develop DIC which is frequently associated with spontaneous bleeding and incoagulable blood. These haemostatic disturbances may be responsible for death or organ/tissue damage both through haemorrhage and microvascular occlusion by fibrin thrombi. The most striking laboratory features of the coagulopathy developing after Russell's viper bite in the 42 patients studied were depletion of fibrinogen (mean 0.09 g/l, range 0-0.6), factor V (6.5 u/dl, range 0-17), factor X (35 u/dl, range 1-85), factor XIIIa (57 u/dl, range 15-82), plasminogen (61 u/dl, range 10-92), antiplasmin (36 u/dl, range 14-62). Protein C (49 u/dl, range 15-100) and platelets (104 x 10(9)/l, range 25-197). Intense fibrinolytic activity was detected in all cases with marked elevation of FDPs (1614 micrograms/ml, range 350-3000), a large proportion of which were cross-linked (1058 micrograms/ml, range 38-3000). The monospecific Burmese antivenom appeared to be very effective in neutralizing the venom procoagulants and in restoring blood coagulability. Moreover, the unexpectedly normal level of AT III provides a theoretical basis for the use of heparin to enhance the inactivation of those serine proteases present before antivenom administration.     

Enzyme enhancement for the measurement of protein C

Protein C measurement is now a necessary work-up of a patient with thrombosis. We described an enzyme enhancement of Laurell's immunoelectrophoresis for assay of protein C antigen. With this modification, the rockets are well defined and easily visualized and the sensitivity of the assay increased (2.5%). Samples with low protein C antigen are easily assayed.     

Anatomical Variations in Stylopharyngeus Muscle Insertions Suggest Interindividual and Left/Right Differences in Pharyngeal Clearance Function of Elderly Patients: A Cadaveric Study

The stylopharyngeus plays a critical role in the clearance of the piriform recess. We dissected 78 sides of the pharynx from 55 donated cadavers and observed histology of another seven sides of the pharynx from seven cadavers. The stylopharyngeus consistently comprised (1) a descending muscle bundle surrounding the piriform recess and (2) an additional short sheet inserting into the tonsillar bed. Histologically, the former bundle connected to a thick fascia providing the lateral glossoepiglottic fold, extending along the submucosa of the piriform recess, and covering the thyroid cartilage, whereas the latter sheet intermingled with other pharyngeal wall muscles at and near the tonsillar bed. Notably, in 44.4% of female specimens, the additional sheet occupied a greater proportion in cross section than the descending muscle bundle. Given the different directions, the additional sheet seemed to check clearance function of the descending bundle for the piriform recess. Thus, particularly in women, interindividual differences in pharyngeal clearance were likely to depend on whether the additional sheet is strong or weak. Chin down in combination with tilting and rotating the head may represent effective exercises of the stylopharyngeus that could compensate for the disadvantages of additional insertion.     

Standardized <Emphasis Type="Italic">Citrus unshiu</Emphasis> peel extract ameliorates dexamethasone-induced neurotoxicity and depressive-like behaviors in mice

Dried Citrus unshiu peel, also known as Chinpi, have been commonly used as a traditional medicine to improve for allergy, inflammation and hepatopathy. Many previously studies have reported that citrus flavonoids show neuroprotective activities. However, the antidepressant-related effects of C. unshiu peels have not been well characterized. Here, the antidepressant-like effects of standardized C. unshiu peel extract (SCP) were evaluated in in vivo and in vitro depression models induced by dexamethasone (DEX), a synthetic glucocorticoid. Male ICR mice (9-week-old) were injected the DEX (40 mg/kg) and were orally given SCP daily (30, 100, and 300 mg/kg) for 14 consecutive days. The depressive-like behaviors were determined by use of open filed test (OFT), sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST). We show that treatment with SCP significantly alleviated DEX-induced depressive-like behaviors and reduced neurotoxicity in a concentration dependent manner in SH-SY5Y cells. Additionally, repeated DEX injection markedly decreased brain derived neurotrophic factor (BDNF) level, tropomyosin receptor kinase B (TrkB), and cyclic AMP-response element-binding protein (CREB), while SCP treatment improved these levels in the cerebral cortex and hippocampus regions. Our findings suggest that SCP exhibits significant antidepressant-like effects in the DEX-induced depressive animal model, and this activity may be mediated by preventing corticosterone-induced neurotoxicity.     

Genetic insight into cytochrome P450 in Chinese from the Chinese Millionome Database

Genetic variations of cytochrome P450 (CYP) influence the inter‐individual differences in drug response. Here, we collected 8682 variants of 57 CYP genes and cytochrome P450 oxidoreductase (POR) from a large‐scale sequencing project in Chinese, Chinese Millionome Database (CMDB). In addition, 52 294 variants from the Genome Aggregation Database (gnomAD) had been simultaneously identified and analysed. Rare variants with a variant allele frequency (VAF) < 0.01 comprised 41.4% (3594/8682) of identified variations in the CMDB, while 98.1% (51 320/52 294) in the gnomAD were rare. Out of 8682 variants in the CMDB, 66.9% (5808/8682) were in introns and only 4.3% (377/8682) were missense variants. In contrast, 36.2% (18 929/52 294) variants in the gnomAD were missense. The common alleles with a VAF over 0.1 were found in CYP1A2*1C, CYP1A2*1F, CYP2C19*2, CYP2D6*2, CYP2D6*10, CYP3A5*3 and CYP4F2*3, with a VAF of 0.161, 0.6, 0.27, 0.274, 0.678, 0.92 and 0.233, respectively. The growing number of genetic variations in CYP genes as more genomes are sequenced would increase the power to predict drug metabolism and response based on the genotype of the particular individual.