The structure and mode of action of different botulinum toxins

The seven serotypes (A–G) of botulinum neurotoxin (BoNT) are proteins produced by Clostridium botulinum and have multifunctional abilities: (i) they target cholinergic nerve endings via binding to ecto‐acceptors (ii) they undergo endocytosis/translocation and (iii) their light chains act intraneuronally to block acetylcholine release. The fundamental process of quantal transmitter release occurs by Ca²⁺‐regulated exocytosis involving sensitive factor attachment protein‐25 (SNAP‐25), syntaxin and synaptobrevin. Proteolytic cleavage by BoNT‐A of nine amino acids from the C‐terminal of SNAP‐25 disables its function, causing prolonged muscle weakness. This unique combination of activities underlies the effectiveness of BoNT‐A haemagglutinin complex in treating human conditions resulting from hyperactivity at peripheral cholinergic nerve endings. In vivo imaging and immunomicroscopy of murine muscles injected with type A toxin revealed that the extended duration of action results from the longevity of its protease, persistence of the cleaved SNAP‐25 and a protracted time course for the remodelling of treated nerve–muscle synapses. In addition, an application in pain management has been indicated by the ability of BoNT to inhibit neuropeptide release from nociceptors, thereby blocking central and peripheral pain sensitization processes. The widespread cellular distribution of SNAP‐25 and the diversity of the toxin's neuronal acceptors are being exploited for other therapeutic applications.     

胶质细胞瘤复发前后Cyclin D1和P16的表达

目的　探讨CyclinD1,P16在胶质瘤复发前后表达改变及其意义。方法　采用免疫组织化学LsABC法对 4 5例复发胶质瘤瘤组织、瘤旁脑组织和 10例正常脑组织CyclinD1,P16蛋白表达进行检测 ,统计分析CyclinD1,P16表达水平与胶质瘤分级、肿瘤复发的关系。结果　正常脑组织 ,瘤旁脑组织和胶质瘤组织CyclinD1表达依次升高 ,而P16的表达依次下降 ;肿瘤复发CyclinD1表达增强 ,P16的表达减弱。结论　CyclinD1与P16的表达与胶质瘤恶性进程和复发密切相关。     

卡托普利对.OH所致异常血流动力学的保护作用

．ＯＨ生成液０．０５ｍｌ．１００ｇ＾－１经胶静脉注入心脏，可使麻醉大鼠的左心室收缩压力、左心室压力与心率乘积、左心室压力上升最大速率和左心室压力下降最大速率明显下降。     

Humeral skeletal development and plasma constituent changes in fetuses of ewes maintained on a low calcium diet from 60 days of gestation

Summary The objective of this study was to evaluate the effects of a long-term, low-calcium diet on fetal calcium metabolism and fetal skeleton skeleton development in ewes. Eleven pregnant sheep were assigned to two groups, fed either a diet low in calcium (0.26% total dry matter) or normal in calcium (0.8% total dry matter) for 2 months, starting at 60 days gestational age. The ewes fed the low calcium diet showed lower plasma levels of calcium and higher plasma levels of hydroxyproline, parathyroid hormone, and 1,25 (OH)₂D compared with the ewes fed the normal calcium diet. There were no differences in these variables between the two groups of fetuses. These observations suggest that the plasma components of calcium homeostasis measured in the fetal lamb in the present study are independent of the ewe and are not significantly affected by the presence of lowere maternal calcium for many weeks during pregnancy. Despite the ability of the fetus of the ewe on the low calcium diet to maintain relatively normal circulating plasma components of calcium homeostasis, long-term maternal hypocalcemia delayed fetal skeletal ossification as shown by histological examination of the fetal humerus. The fetal humerus from low calcium-fed ewes showed a lower proportion of bone versus cartilage (45.6±5.9 versus 57.4±4.6%, mean ±SD) lower ash content (15.4±1.5 versus 17.4±1.0%), and lower specific gravity (1.19±0.2 versus 1.22±0.02) (P<0.05) than the humerus from fetuses of normal calcium-fed ewes. This study shows that the long-term calcium intake of the ewe does affect fetal skeletal development, despite a lack of observable effects on fetal plasma concentrations of calcium or known calcium regulating hormones such as 1,25(OH)₂D or parathyroid hormone.     

CT angiography in carotid stenosis

Purpose: Prospective evaluation of the accuracy of CT angiography (CTA) with different postprocessing for extracranial carotid artery in comparison with DSA. Method: one hundred patients were studied with standarized CTA. For postprocessing, MPR, MIP, and 3D reconstruction based on segmentation with upper and lower threshold were used. Intravascular density profiles were considered. All CTA studies were correlated with intra-arterial angiography. The degree and classification of stenoses was determined using the guidelines established by the NASCET collaborators. Results: Measurement of stenosis was possible by MPR in 82.5 %, by MIP in 85 %, and 3D in 100 %. Correct classification was found in 65.5 % for MPR, 66 % for MIP and 88.5 % for 3D. The sensitivity for severe stenoses was 74 % for MPR, 82 % for MIP, and 93 % for 3D. The specificity of these methods was 98 %, 96 %, and 97 %, respectively. All carotid occlusions were correctly identified, no carotid artery was wrongly classified as occluded. Conclusions: CT angiography allows reliable examinations in carotid artery stenoses and occlusions. 3D reconstruction based on threshold segmentation is superior to MPR and MIP. In some circumstances, e.g., carotid occlusion, further investigation by invasive procedures is not necessary.      

微量元素锌在佝偻病治疗中的效果观察

目的 :探讨补充锌 +维生素D +钙剂治疗佝偻病的效果。方法 :随机分为 3组 ,每组各 5 3例。对照组给予常规治疗 (即维生素D +钙剂 ) ,治疗 1组先给予锌治疗 1个月后 +常规治疗 ,治疗 2组同时给予锌 +常规治疗。 3个月为 1疗程。治疗前后检测血清微量元素及骨碱性磷酸酶 (BALP)等项目。结果 :治疗 1、2组疗效好于对照组 ,差异非常显著 (P <0 0 1) ;治疗1组疗效好于治疗 2组 ,差异有显著性 (P <0 0 5 )。结论 :治疗大多数伴低锌的佝偻病先补锌 1个月 ,再加常规治疗 ,疗效更佳。     

Enhanced stimulus-reward learning by intra-amygdala administration of a D3 dopamine receptor agonist

The amygdala is considered to be a critical neural substrate underlying the formation of stimulus-reward associations, and is known to receive substantial innervation from dopaminergic neurons located within the ventral mesencephalon. However, relat- ively little is known about the function of the mesoamygdaloid dopamine projection in stimulus-reward learning. Recently, we have found post-session intra-amygdala microinjections of d-amphetamine to enhance appetitive Pavlovian conditioning as assessed in a discriminative approach task. In the present study, we have examined the effects of dopamine receptor agonists possessing relative selectivity for the D₁, D₂ and D₃ receptor subtypes in order to examine more fully the role of the mesoamygdaloid dopamine projection in stimulus-reward learning. Thus, subjects were trained to associate an initially neutral stimulus (CS⁺) with 10% sucrose reward (US). A second, control stimulus (CS⁻) was also presented but never paired with sucrose reward. In order to measure specifically the conditioned response to CS⁺/CS⁻ presentation, responding during CS and US presentations was measured separately. Immediately following each training session, subjects received bilateral intra-amygdala infusion of 0.1, 1 or 10 nmol/side of SKF-38393, quinpirole or 7-OH-DPAT. Infusions of SKF-38393 or quinpirole were without effect on CS⁺ approach. However, post-session intra-amygdala infusions of 7-OH-DPAT enhanced selectively CS⁺ approach in a dose-dependent fashion. No dose of any drug affected CS⁻approach, US behaviours, or measures of extraneous behaviour. Subsequent acquisition of a novel conditioned instrumental response was also unaffected. Thus, the present data indicate a selective involvement of the D₃ dopamine receptor subtype in the modulation of stimulus-reward learning by the mesoamygdaloid dopamine projection. Received: 12 December 1996 / Final version: 9 April 1997     

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T₂-weighted fast spin-echo (FSE), and T₁-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T₁ based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.     

胃复春片对慢性胃病患者窦D细胞的影响

目的：探讨胃复春片治疗慢性胃病患者前后生长抑素内分泌细胞(D细胞)数量变化。方法：用免疫组化酶链亲合素过氧化酶复合技术(SABC)对患者治疗前后胃粘膜组织的D细胞染色，观察治疗前后D细胞的形态和数量变化。结果：经胃复春片治疗后，患者胃窦粘膜D细胞阳性数及强阳性率均明显下降，有显著意义。结论：胃复春片对慢性胃病患者生长抑素D细胞有调整作用。     

[H](+)S 14297: A novel, selective radioligand at cloned human dopamine D3 receptors

The selective dopamine D₃ receptor antagonist [³H](+)S 14297 ((+)-[7-(N,N-dipropylamino)-5,6,7,8-tetrahydro-naphtho(2,3b)dihydro,2,3-furane]), labelled to high specific activity (145 Ci/mmol), bound to cloned human dopamine D₃ receptors but displayed negligible binding to cloned human D₂ receptors. [³H](+)S 14297 exhibited rapid association and dissociation, high affinity saturable binding (K_d = 7.0 nM) and a competition binding profile highly correlated with that of [¹²⁵I]iodosulpride (r = 0.98).