神经细胞营养（诱向）因子与运动神经元疾病

本文从神经营养（诱向）因子有选择地保障运动神经元健康存活和执行功能，防止它凋亡和损伤所引起的神经元退变及促进其再生等生物学效应，结合运动神经元病的病理退变的主要特点及本实验室对运动神经元营养（诱向）因子的工作，综述了这方面的新进展，期望对探索运动神经元病的病因和治疗提供新的线索和可能性。     

Brushing with and without dentifrice on gingival abrasion

OBJECTIVES: This study was designed to evaluate two factors possibly influencing incidence of gingival abrasion during toothbrushing: (1) the abrasiveness of a dentifrice and (2) the possible influence of feedback of oral sensory perception. MATERIAL AND METHODS: For this purpose, two separate, single blind, randomized clinical experiments were performed. The two groups of subjects were requested not to brush their teeth 48 h, prior to the experiments. After staining with disclosing solution gingival abrasion sites were recorded as small (< or =5 mm) and large (>5 mm), both before and after brushing. The dentifrice experiment was a split-mouth design, including 36 subjects, brushing their teeth in two randomly selected contra-lateral quadrants, either with or without dentifrice, whereas the remaining two quadrants were brushed, using the alternative choice. The sensory perception feedback experiment was a full-mouth design, including 43 subjects and two separate brushing exercises with use of dentifrice. The first brushing-exercise was performed by a dental hygienist, excluding the feedback of oral sensory perception of the brusher. After a 4 weeks period of familiarization to the manual toothbrush, subjects brushed themselves in the same random order as the hygienist, using a fresh brush, thus including oral sensory perception. RESULTS: In the dentifrice experiment, the increment of small abrasion sites was 5.86 for brushing with and 5.75 without dentifrice. There was no statistically significant difference between brushing with and without dentifrice. Both with and without dentifrice, more small abrasions were found vestibular, (3.78 and 4.22, respectively) as compared with lingual (2.22 and 1.42, respectively) (p=0.027, p<0.001). In the sensory perception feedback experiment, the increment in small gingival abrasion sites was larger for the subjects brushing themselves (8.86) as compared with the professional brushing (2.94, p <0.0001). Subjects caused more abrasion on the vestibular surfaces (6.28) as compared with the lingual (0.60, p=0.0001), where the professional did not show this difference (vestibular: 1.88, lingual: 1.30, p=0. 1388). CONCLUSIONS: No statistically significant difference in the incidence of gingival abrasion was found between brushing with dentifrice or without dentifrice. Neither did oral sensory perception seem to affect the incidence of gingival abrasion.     

Heterogeneity of heparan sulfates in human lung

Heparan sulfates (HS), a class of glycosaminoglycans, are long linear complex polysaccharides covalently attached to a protein core. The HS molecules are made up of repeating disaccharides onto which modification patterns are superimposed. This results in a large structural heterogeneity and forms the basis of specific interactions of HS toward a vast array of proteins, including growth factors and proteases. To study HS heterogeneity in the lung, we used phage display technology to select seven antibodies against human lung HS. Antibodies reacted with HS/heparin, but not with other glycosaminoglycans or polyanions. Sulfate groups were essential for antibody binding. The amino acid sequence of the antibodies was established, the complementarity determining region 3 of the heavy chain containing basic amino acids. The antibodies defined HS epitopes with a characteristic tissue distribution. Antibody EV3A1 primarily stained macrophages. Other antibodies primarily stained basement membranes, but with different preference toward type of basement membrane. Antibody EV3C3 was the only antibody which clearly reacted with bronchiolar epithelial cells. In human lung parenchyma, basic fibroblast growth factor and vascular endothelial growth factor were largely bound by HS. Some antibodies blocked a basic fibroblast growth factor-binding site of HS, and one antibody blocked a vascular endothelial growth factor-binding site of heparin. Taken together, these data suggest a specific role for HS epitopes in human lung. The antibodies obtained may be valuable tools to study HS in pulmonary diseases.     

Blood coagulation and the risk of atherothrombosis: a complex relationship

The principles of Virchov's triad appear to be operational in atherothrombosis or arterial thrombosis: local flow changes and particularly vacular wall damage are the main pathophysiological elements. Furthermore, alterations in arterial blood composition are also involved although the specific role and importance of blood coagulation is an ongoing matter of debate. In this review we provide support for the hypothesis that activated blood coagulation is an essential determinant of the risk of atherothrombotic complications. We distinguish two phases in atherosclerosis: In the first phase, atherosclerosis develops under influence of "classical" risk factors, i.e. both genetic and acquired forces. While fibrinogen/fibrin molecules participate in early plaque lesions, increased activity of systemic coagulation is of no major influence on the risk of arterial thrombosis, except in rare cases where a number of specific procoagulant forces collide. Despite the presence of tissue factor - factor VII complex it is unlikely that all fibrin in the atherosclerotic plaque is the direct result from local clotting activity. The dominant effect of coagulation in this phase is anticoagulant, i.e. thrombin enhances protein C activation through its binding to endothelial thrombomodulin.The second phase is characterized by advancing atherosclerosis, with greater impact of inflammation as indicated by an elevated level of plasma C-reactive protein, the result of increased production influenced by interleukin-6. Inflammation overwhelms protective anticoagulant forces, which in itself may have become less efficient due to down regulation of thrombomodulin and endothelial cell protein C receptor (EPCR) expression. In this phase, the inflammatory drive leads to recurrent induction of tissue factor and assembly of catalytic complexes on aggregated cells and on microparticles, maintaining a certain level of thrombin production and fibrin formation. In advanced atherosclerosis systemic and vascular wall driven coagulation becomes more important and elevated levels of D-dimer fragments should be interpreted as markers of this hypercoagulability.     

沙苑子化学成分的研究Ⅱ

沙苑子为豆科黄芪属植物扁茎黄芪(Astragalus complanatus R.Brown)的种子,有益肾固精、补肝明目之功能。有关沙苑子的化学成分,除本文作者曾从水溶液中分离得到氨基酸外,其他化学成分的研究尚未见报道。本文从脱脂沙苑子的乙醇提出物中分得一新的黄酮甙,确定为鼠李柠檬素-3,4′-O-β-D-双葡萄糖甙,命名为沙苑子甙(complanatuside)。     

落新妇和岩菖蒲中岩白菜素的高效液相色谱测定法

本文报道用高效液相色谱法测定落新妇和岩菖蒲中岩白菜素的含量。样品用甲醇以超声波法提取,通过YWG-C₁₈H₃₇键合相柱,用甲醇—乙醚—乙腈—水(30:2:3:65)为流动相,在275nm波长检测,用对氨基苯磺酸为内标,峰面积内标法定量。方法简便,快速,结果较好。     

Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers

The effect of hematoporphyrin derivative photoradiation on tumor and normal tissue microcirculation was studied microscopically in vivo on rats with mammary carcinomas transplanted into subcutis in transparent observation chambers. One day after i.p. injection of hematoporphyrin derivative (15 mg/kg), chambers were exposed to red light (632 +/- 2 nm, eight light dose values, 0 to 270 J/cm2). After an initial blanching (ischemia) of the tumor accompanied by apparent vasoconstriction, reperfusion was observed with a slowing down of the tumor circulation, vasodilatation, and eventually a complete stasis, together with diffuse hemorrhages and subsequent necrosis. Besides, in large normal tissue vessels, platelet aggregates were observed, but no hemorrhage. Tumor regrowth occurred unless the tumor circulation and the adjacent normal tissue circulation were both destroyed. Tumor cell viability after treatment was assessed by transplanting the tumor from the chamber into the flank of the same animal. Even after a combined porphyrin and light dose 4 times the lethal dose for all tissues in the chamber, five of five transplanted tumors did regrow. This leads to the conclusion that, in our model system, tumor cell death after photoradiation occurs secondary to destruction of the microcirculation. In order to obtain additional information on normal tissue damage, rat ears were also irradiated. For the same light dose, the biological effect was only slightly larger than that of the normal tissue in the observation chambers, even though the measured ratio of porphyrin concentrations in ears and normal tissue in the chambers (subcutis) was about six.     

Intra-aortic balloon pump in patients with ischaemic heart disease undergoing oesophagogastrectomy

Background Oesophagogastrectomy for carcinoma has a high operative mortality rate. Patients are elderly and ischaemic heart disease (IHD) is a recognised and frequent risk factor. Aim To illustrate the use of the intra-aortic balloon pump (IABP) as prophylaxis against cardiac complications in a group of such patients. Methods Five patients aged from 63 to 78 years were presented with operable adenocarcinoma of the oesophagus. They had IHD of a severity thought to pose a risk of myocardial infarction (MI) and/or failure at the time of oesophagogastrectomy. With the induction of anaesthesia, the IABP was inserted and left in situ for up to 24 hours. Results There were no major adverse perioperative cardiac events. Four patients were discharged from hospital on the eighth and one on the tenth postoperative day. Conclusion The prophylactic use of IABP has a potential role in the prevention of cardiac complications in patients with IHD undergoing high risk non-cardiac surgery.     

MPP5 recruits MPP4 to the CRB1 complex in photoreceptors

PURPOSE: Mutations in the human Crumbs homologue 1 (CRB1) gene are a frequent cause of Leber congenital amaurosis (LCA) and various forms of retinitis pigmentosa. CRB1 is thought to organize an intracellular protein scaffold in the retina that is involved in photoreceptor polarity. This study was focused on the identification, subcellular localization, and binding characteristics of a novel member of the protein scaffold connected to CRB1. METHODS: To dissect the protein scaffold connected to CRB1, the yeast two-hybrid approach was used to screen for interacting proteins. Glutathione S-transferase (GST) pull-down analysis and immunoprecipitation were used to verify protein-protein interactions. The subcellular localization of the proteins was visualized by immunohistochemistry and confocal microscopy on human retinas and immunoelectron microscopy on mouse retinas. RESULTS: A novel member of the scaffold connected to CRB1, called membrane palmitoylated protein (MPP) subfamily member 4 (MPP4), a membrane-associated guanylate kinase (MAGUK) protein, was identified. MPP4 was found to exist in a complex with CRB1 through direct interaction with the MPP subfamily member MPP5 (PALS1). 3D homology modeling provided evidence for a mechanism that regulates the recruitment of both homo- and heterodimers of MPP4 and -5 proteins to the complex. Localization studies in the retina showed that CRB1, MPP5, and MPP4 colocalize at the outer limiting membrane (OLM). CONCLUSIONS: These data imply that MPP4 and -5 have a role in photoreceptor polarity and, by association with CRB1, pinpoint the cognate genes as functional candidate genes for inherited retinopathies.