Membrane-associated guidance cues direct the innervation of forebrain and midbrain by dorsal raphe-derived serotonergic axons

Unlike many neurons that extend an axon precisely to a single target, individual dorsal raphe 5-HT neurons project to multiple brain regions and their axon terminals often lack classical synaptic specializations. It is not known how 5-HT axon collaterals select between multiple target fields, or even if 5-HT axons require specific guidance cues to innervate their targets. Nor is it known how these axon collaterals are restrained within specific innervation target regions. To investigate this, we challenged explants of dorsal raphe with co-explants, or cell membrane preparations of ventral midbrain, striatum or cerebral cortex. We provide evidence for membrane-associated cues that promote 5-HT axon growth into each of these three target regions. The axon growth-promoting activity was heat-, protease- and phosphatidylinositol-phospholipase-C (PI-PLC)-sensitive. Interestingly, 5-HT axons specifically lost the ability to grow in heterotypic explants, or membrane carpets, following contact with ventral midbrain or striatal, but not cortical, explants or membranes. This inductive activity associated with striatal and ventral midbrain membranes was sensitive to both high salt extraction and PI-PLC treatment. By contrast, the activity that inhibited 5-HT axon growth onto heterotypic membranes was sensitive only to high salt extraction. These results provide evidence that a glycosylphosphatidylinositol (GPI)-linked membrane protein promotes 5-HT axon growth, and that short-range membrane-bound, as well as GPI-linked, molecules contribute to the guidance of 5-HT axon collaterals. These findings suggest that 5-HT axon collaterals acquire a target-induced growth-inhibitory response to alternative targets, increasing their selectivity for the newly innervated field.     

Nucleotide Sequences of the 3′ Terminal Region of Onion Yellow Dwarf Virus Isolates from Allium Plants in Japan

The 2032 nucleotide sequence of the 3′ terminal region of onion yellow dwarf virus (OYDV) isolated from Allium wakegi, bearing the genes for viral coat protein (CP) and a truncated RNA-dependent RNA polymerase, has been determined. Respecive homologies of the nucleotide sequence in the corresponding region and the deduced amino acid sequence of CP with the equivalents of leek yellow stripe virus (LYSV) from garlic were 68.0 and 59.3%. Variation in the nucleotide sequence is concentrated in the boundary region between the putative RNA-dependent RNA polymerase gene and the CP gene as well as in the 3′ noncoding region. These sequence divergencies, including the deletion of 79 nucleotides, resulted both in alterations to the amino acid sequence and the absence of 28 amino acid residues in the amino terminal region of OYDV CP in comparison with LYSV CP. In addition, the lenght of the 3′ noncoding sequence of OYDV was one-third that of LYSV. Comparison of the 3′ terminal 1197 nucleotides sequence of OYDV with sequences of the respective cDNAs cloned by RT-PCR directly from the total RNA of infected Allium plants that included two varieties of A. fistulosum, “Wakenegi' and “Shimonita-negi”, and A. chinense, showed 90.7% overall identities, even though they have long been cultivated in locally restricted area in Japan. These findings appear to suggest that a single strain of OYDV invaded Japanese Allium plants long ago and spread throughout them. This revised version was published online in July 2006 with corrections to the Cover Date.     

�����ɺ͸�����ֲ���ҩ���ƿ�ǻ�����ͱ�ƽ̦޺����Ч�۲�

目的观察氟美松和甘美达局部用药治疗口腔斑纹型扁平苔藓的疗效。方法选择2006年10月至2007年10月中国医科大学口腔医学院综合急诊科就诊的口腔斑纹型扁平苔藓患者185例,随机分成4组,各组采用不同药物患处涂抹。A组用氟美松与甘美达凝胶混合均匀后患处涂抹,B组用氟美松患处涂抹,C组用甘美达凝胶患处涂抹,D组用口腔溃疡散患处涂抹,观察1～3周,对各组白色斑纹面积、充血面积的变化以及有效率进行对比分析。结果1周后A组斑纹面积缩小率达到48.68%,充血面积缩小率达到50.25%,有效率达到70.0%,斑纹面积缩小率和有效率与其他各组比较,差异有统计学意义(P<0.05),充血面积缩小率与其他各组比较差异无统计学意义(P>0.05)。2周后A组斑纹面积缩小率达到89.73%,充血面积缩小率达到84.69%,有效率达到92.0%,与其他组比较差异均有统计学意义(P<0.05)。结论氟美松和甘美达联合患处涂抹治疗口腔斑纹型扁平苔藓具有良好的临床疗效。     

Fumonisin B1 and the kidney: Modes of action for renal tumor formation by fumonisin B1 in rodents

The mycotoxin fumonisin B₁ (FB₁) is an important contaminant of maize and maize-based products. In rodent toxicity studies, FB₁ was shown to be hepato- and nephrotoxic, and to induce renal tumors in rats when administered via the diet. Of particular note are the aggressive growth characteristics of FB₁-induced tumors with a high potential to metastasize. While genotoxicity does not appear to contribute to FB₁ carcinogenicity, it is well established that FB₁-mediated disruption of sphingolipid metabolism plays a key role in FB₁ toxicity. This review provides an overview on human dietary exposure to FB₁, FB₁ toxicity and carcinogenicity, and potential mechanisms involved in FB₁-mediated tumor formation, with a particular focus on cellular functions of sphingolipids and biological consequences of FB₁-mediated perturbation of sphingolipid metabolism.     

Influence of endothelin 1 on human atrial myocardium—myocardial function and subcellular pathways

The influence of endothelin 1 on isometrically contracting human atrial muscle strip preparations was investigated under physiological conditions (37°C, 1 Hz, Ca²⁺ 2.5 mM). Endothelin dose-dependently increased isometric tension from 3×10^–10M to 1×10^–7M. At 1×10^–7M the inotropic effect of endothelin was maximum with isometric tension being increased by 32±6% (n=11, p<0.05). At 1×10^–7M endothelin the positive inotropic effect was preceded by a transient negative inotropic effect with a decline in tension by –5±1% (n=11, p<0.05). Endothelin prolonged time from peak tension to 50% relaxation (RT50) by 29±5%. With BQ123 a competitive antagonist of the ET_A receptor positive inotropic effect and the prolongation of relaxation was significantly reduced and initial negative inotropic effect was abolished, indicating a ET_A receptor mediated effect. Preincubation with phorbolmyristateacetate (10^–5M) to downregulate proteinkinase C (PKC) eliminated the positive inotropic effect of endothelin. Similarly, N-5,5-dimethylamiloride (10^–5M) which inhibits Na⁺/H⁺-exchanger activity, abolished the positive inotropic effect of ET. However, with either PMA or DMA the initial transient negative inotropic effect was still present (–13±7%, n=9, p<0.05 and –3±1%, n=6, p<0.05). Furthermore, both substances did not abolish the prolongation of twitch time parameters observed under endothelin. After preincubation with PMA, endothelin prolonged RT50 by 18±6% and with DMA by 11±2%. Using the photoprotein aequorin as an indicator for intracellular calcium concentrations showed that the positive inotropic effect was mainly mediated by an increase of systolic intracellular calcium concentrations. Thus, the present data indicate that the positive inotropic effect of endothelin in human atrial myocardium results from activation of PKC with a subsequent activation of the Na⁺/H⁺-exchanger. However, the initial negative inotropic effects as well as the prolongation of relaxation seem to result from a different intracellular mechanism of endothelin.     

眶骨膜瓣矫治固定性内斜视

目的 探讨固定性内斜视的手术治疗方式.方法 采用眼眶骨膜瓣锚定术加强外直肌矫治固定性内斜视18例(24眼).通过内直肌断腱术外直肌缩短联合眶骨膜瓣锚定术加强外直肌的综合手术治疗方式,矫治固定性内斜视眼位.结果 18例(24眼)均取得良好效果.除2眼内斜欠矫5°～10°外,其他术后眼位居中,眼位均较术前明显改善.其中12眼术后矫正视力0.2 ～0.4,基本恢复了视功能,其余则达到了美容效果,术眼可轻度外转,眼球运动灵活且自然.无1例过矫或发生垂直性斜视,随访1～5年,无1例复发,无感染等并发症.结论 由于眶骨膜作为有良好血运活体的组织瓣,而且眶骨膜是自身组织,不具有抗原性,又临近术区,具备良好的取材优势.质地坚韧,不会发生吸收变形,眶骨膜瓣矫治固定性内斜视是一种安全有效的治疗方式,美容效果显著而且自然,近远期效果稳定良好.     

Eph receptor–ligand interactions are necessary for guidance of retinal ganglion cell axons in vitro

Previous results of an in vitro guidance test, the stripe assay, have demonstrated the presence of a repulsive axon guidance activity for temporal retinal axons in the posterior part of the vertebrate optic tectum. Ephrin-A5 and Ephrin-A2 are ligands for the EphA subfamily of Eph receptor tyrosine kinases, which are expressed in overlapping gradients in the posterior part of the tectum. When recombinantly expressed, both proteins have been shown to guide retinal ganglion cell axons in the stripe assay. While these results suggest that Ephrin-A5 and Ephrin-A2 form part of the posterior repulsive guidance activity, they do not elucidate whether they are necessary components. Here we report that soluble forms of the ligands at nanomolar concentrations completely abolish this repulsive activity. Similar results were obtained with the soluble extracellular domain of EphA3, which is a receptor for Ephrin-A2 and Ephrin-A5, but not with the corresponding domain of EphB3, a receptor for the transmembrane class of Eph ligands. These experiments show that the repulsive axon guidance activity seen in the stripe assay is mediated by Ephrin-A ligands.     

Stripe sign in pulmonary embolism: A review of the causes

The most common indication for radionuclide imaging of lungs is the evaluation of suspected pulmonary thromboembolism (PE). Scintigraphically PE classically produces ventilation/perfusion mismatch, that is perfusion defects in areas showing normal ventilation. Stripe sign refers to the visualization a stripe at normally perfused lung interposed between a defect and adjacent pleural surfaces as originally described by Gottschalk. In the present case the authors describe a patient with a ventilation/perfusion scan suggesting PE. She also had a stripe sign on the perfusion scan with normal ventilation. On the follow-up perfusion scintigraphy, normal perfusion was seen in the corresponding area. The literature on stripe sign is also reviewed.     

乳化型鼻用纱条的研制及临床作用

 目的制备乳化型止鼻血纱条，建立质量控制标准，观察其对各种原因所致的鼻出血的止血、抗炎效果。方法筛选合理的处方，制备止血纱条，以鉴别和主药含量测定控制其质量，临床验证600例并设两组对照组观察其疗效。结果治疗组(600例)总有效率为98.83%，对照一组(156例)总有效率为76.28%(P＜0.01)；对照二组(123例)总有效率为73.17%(P＜0.01)。结论乳化型鼻用纱条止鼻血疗效确切，抗炎作用明显，临床应用前景广阔。