Tacrine restores cholinergic nicotinic receptors and glucose metabolism in alzheimer patients as visualized by positron emission tomography

Three patients with Alzheimer's disease, a 68-year-old woman with mild dementia and 2 men (aged 64 and 72 years) with moderate dementia were treated orally with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine), 80 mg daily, for several months. The patients were investigated using positron emission tomography (PET) prior to, and after 3 weeks and 3 months of treatment. The PET studies involved a multi-tracer system consisting of [¹⁸F]-fluoro-deoxy-glucose (¹⁸F-FDG) (tracer for glucose metabolism); ¹¹C-butanol (cerebral blood flow) and (S)(−)- and (R)(+)-[N-¹¹C-methyl]-nicotine (nicotinic receptors; cholinergic neural activity). Tacrine treatment increased the uptake of ¹¹C-nicotine to the brain. Significant reduced difference in uptake between the two enantiomers (S)(−)- and (R)(+)¹¹C-nicotine was observed in the frontal and temporal cortices after tacrine treatment in all three patients. The kinetic analysis indicated increased binding of (S)(−)¹¹C-nicotine in brain compatible with a restoration of nicotinic cholinergic receptors. The most pronounced effect was observed after 3 weeks and 3 months treatment in the patient with mild dementia. An increase in cerebral glucose utilization was found in the 68-year-old patient with mild dementia but also slightly in the 64-year-old man with moderate dementia when treated with tacrine for 3 months. Tacrine administration did not affect cerebral blood flow. The PET data obtained after 3 weeks of tacrine treatment was paralleled by improvement in neuropsychological performance. This study shows in vivo by PET neurochemical effects induced in brain by treatment with tacrine to Alzheimer patients. Intervention with tacrine in the early course of the disease might be necessary for clinical improvement.     

Effects of convergent strabismus on spatio-temporal response properties of neurons in cat area 18

Summary Single-cell recording experiments were carried out to determine whether rearing kittens with surgically induced convergent strabismus (esotropia) alters the development of receptive field (RF) properties of neurons in area 18. In agreement with previous work on kittens with divergent strabismus (exotropia), there was a marked loss of binocularly driven cells in area 18 of esotropic cats. In contrast to the striate cortex of strabismic cats, the spatial properties of area 18 neurons, including receptive-field size and spatial frequency tuning, did not differ from those in normal controls. On the other hand, we found that contrast thresholds, measured at an optimal spatial frequency, were significantly elevated, and that the contrast gain in many cells was reduced in strabismic cats. These deficits were observed in both eyes, though the cells dominated by the deviating eye had a lower response amplitude at all contrasts. Furthermore, temporal frequency tuning curves were abnormal in strabismic cats in that the optimal frequencies and temporal resolutions were shifted to lower values. These effects were also bilateral. Velocity tuning, measured with a high-contrast bar stimulus, revealed that area 18 neurons in strabismic cats were unable to respond to very high velocities compared to normals. This reduced response was more severe when measured with the deviating eye in spite of the bilateral nature of the deficit. Finally, latencies to electrical stimulation of the optic chiasm or the optic radiation were significantly longer in strabismic cats. The magnitude of these effects was virtually the same for both eyes. From these observations, we conclude that the temporal properties of area 18 neurons, particularly the cells abilities to follow fast temporal modulations, are affected by raising kittens with surgically induced convergent strabismus.     

IL-18、ICE在人卵巢癌组织中的表达

目的:分析卵巢癌组织中白细胞介素18(IL-18)及白细胞介素1β转化酶(ICE)的基因及蛋白表达水平,探讨其与卵巢癌临床特性之间的关系.方法:分别采用RT-PCR及免疫组化染色法检测正常卵巢(n=10)、卵巢良性肿瘤(n=6)、卵巢癌(n=32)组织中IL-18、ICE的mRNA及蛋白表达;分析卵巢癌不同病理类型、临床分期及发病年龄患者之间表达是否具有差异.结果:①正常、良性肿瘤及卵巢癌组织中均有IL-18 mRNA表达(分别为1.30±0.48、1.02±0.17、0.77±0.35);ICE mRNA在正常及良性肿瘤组织中均有表达,卵巢癌组织中有29例(90.63%)表达(分别为0.96±0.51、0.73±0.34、0.63±0.34).②IL-18及ICE蛋白均表达于卵巢上皮细胞浆内.正常、良性肿瘤及卵巢癌组织的IL-18阳性表达率分别为83.3%、80.0%和31.3%;ICE阳性表达率分别为80.0%、50.0%和37.5%.③卵巢癌组织中IL-18、ICE mRNA及蛋白表达均较正常及良性肿瘤组织明显减少(均P＜0.05),良性与正常组织之间相比差异均无显著性(均P＞0.05).卵巢癌组织中IL-18与ICE的mRNA、蛋白表达之间呈显著正相关(分别为r=0.37,P=0.036;r=0.45,P=0.009).④IL-18、ICE mRNA及蛋白表达在不同病理类型、临床分期及发病年龄患者之间均未见显著性差异(均P＞0.05).结论:卵巢癌患者局部癌组织IL-18、ICE表达减弱,可能与卵巢癌的发生发展有着一定的关系.     

Differentiation markers of Sertoli cells and germ cells in fetal and early postnatal human testis

The definition of the temporal sequence of appearance of fetal markers during prenatal and early postnatal development in Sertoli and germ cells may be important for understanding the mechanisms underlying their reexpression in disorders of the adult testis. For this reason, we studied the expression of Sertoli and germ cell markers in 25 human testes spanning a period from 8 gestational weeks to 4 years. Well-characterized antibodies were employed to anti-Müllerian hormone (AMH), cytokeratin 18 (CK18), vimentin (VIM), M2A-antigen (M2A), germ cell alkaline phosphatase (GCAP), and somatic angiotensin-converting enzyme (sACE) on formalin-fixed and microwave-pretreated paraffin sections. In Sertoli cells, AMH and VIM were consistently present. While VIM and CK18 were coexpressed in embryonic testes, CK18 was progressively downregulated and completely absent from the 20th gestational week. M2A was absent or moderately expressed in fetal Sertoli cells but increased during further development. In germ cells, M2A was consistently found in primordial germ cells (PGCs) as well as in M- and T₁-prespermatogonia. In contrast, sACE and GCAP were absent from PGCs but were a distinct feature of late M- and early T₁-prespermatogonia and appeared predominantly between the 18th and the 22nd gestational weeks. Both T₂-prespermatogonia and postnatal prespermatogonia were devoid of any marker. While CK18 represents a differentiation marker for fetal Sertoli cells, M2A, GCAP, and sACE can be used as differentiation markers for the discrimination of different germ cell types during human prespermatogenesis. Because various immunophenotypes reflect distinct differentiation stages, this knowledge may be important for understanding adult testicular pathology.     

pcDNA3.1/hIL-18真核表达载体的构建及表达

目的 :构建重组真核表达质粒pcDNA3.1/IL 18,并在哺乳动物细胞COS 7和Rlc310中进行瞬时和稳定性表达。方法 :从含hIL 18基因的中介载体 pGEM TEasy( pGEM T/hIL 18)中 ,以限制性内切酶酶切方法获得目的片段 ,克隆入真核表达质粒 pcDNA3.1( )中。以脂质体法转染COS 7和Rlc310细胞 ,用RT PCR检测IL 18mRNA的水平 ,免疫组化染色法检测蛋白表达。结果 :构建了hIL 18基因的重组真核表达质粒pcDNA3.1/IL 18,并可在哺乳动物细胞中瞬时、稳定表达 ,获得了可稳定表达hIL 18基因的Rlc310细胞株。结论 :pcDNA3.1/IL 18的构建及表达 ,为IL 18抗肿瘤作用的研究奠定了基础     

卡巴胆碱抑制肿瘤坏死因子所致微血管内皮细胞通透性增高

目的探讨卡巴胆碱对肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）诱导的增加微血管通透性的作用。方法采用FITC标记白蛋白漏出法、考马斯亮蓝染色法观察卡巴胆碱对TNF-α诱导微血管内皮细胞通透性，细胞形态和细胞骨架变化的影响。结果与对照组比较，TNF-α明显增加微血管内皮细胞通透性（P〈0．05），诱导细胞皱缩，细胞间隙增大和细胞骨架排列紊乱。给予卡巴胆碱可以明显抑制TNF-α诱导微血管内皮细胞通透性增加，并呈剂量依赖性，同时可以使细胞间隙明显减小，细胞骨架排列有序。结论卡巴胆碱可能通过抑制TNF-α对细胞骨架的损伤，进而抑制微血管通透性增加。     

Activation of human neutrophils by the pollutant sodium sulfite: effect on cytokine production,chemotaxis, and cell surface expression of cell adhesion molecules

In chronic beryllium disease (CBD), a granulomatous lung disease characterized by hypersensitivity to beryllium salts (BE), BE challenge of bronchoalveolar lavage cells induces IFNgamma. Although nitric oxide (NO) is elevated in CBD airways, the effects of NO on CBD IFNgamma responses are unknown. Here we report that BE-stimulated IFNgamma production in CBD lavage cells was markedly reduced (74%) by the NO generator DETA NONOate. Investigation of IFNgamma-stimulatory cytokine involvement indicated that lavage cell IL-18 was significantly increased (fourfold) by BE and reduced (64%) by DETA NONOate but IL-12 was undetectable. IL-18 production was caspase-1-dependent but caspase 1 inhibition reduced IFNgamma only partially (43%). Specific antibody depletion of lavage cell IL-18 yielded marginal reduction (19%) of IFNgamma. Data are the first to show that: (1) BE stimulates IL-18 as well as IFNgamma in CBD; (2) BE cytokine responses are NO-sensitive; and (3) NO down-regulation of IFNgamma involves other sites in addition to IL-18.     

Postnatal development of somatostatin-containing neurons in the visual cortex of normal and dark-reared rats

Summary The distribution of somatostatin (SRIF)-immunoreactive neurons in the visual cortical areas 17, 18 and 18a of Wistar rats from birth to adulthood was followed in both normal and dark-reared animals. The SRIF neurons show difference in distribution amongst the three cortical areas studied as early as the first postnatal week. Area 17 was distinguished by fewer SRIF cells in the upper layers (I–III), which results in a lower overall density. The SRIF neurons in all areas appeared to increase in numbers up to about 3 weeks and then decline dramatically to adult levels, which were 14–19% of the peak levels. Although this decline was still obvious, it moderated to 25–31% in dark-reared animals. The greatest effect was seen in area 18 where, at 60 days of age, there were twice as many SRIF cells in darkreared as in normal controls. It is suggested that, under conditions of dark rearing, the overall pattern of development of SRIF neurons, being uninfluenced by extrinsic factors, reveals the cells' genetic potential.     

严重烧伤患者血清IL-18、sFas和sFasL水平的变化规律及其相关性研究

目的 :探讨严重烧伤患者血清IL 18、sFas和sFasL水平间的变化及其与病情的关系。方法 :选择烧伤总面积(TBSA)≥ 30 %的严重烧伤患者 30例 ,其中死亡 3例 ;正常对照组 4 5例。采用ELISA法对不同时相点 (伤后 1、3、5、7、14、2 1、2 8和 35天 )患者血中IL 18、sFas和sFasL水平进行检测。结果 :与正常对照组比较 ,患者血清IL 18、sFas和sFasL水平均呈显著性上升 (P <0 0 1～ 0 0 5 ) ,并分别持续至伤后 2 8,2 1和 2 1天 ;感染组患者血清IL 18、sFas和sFasL水平均显著地高于非感染组 (P <0 0 1～ 0 0 5 ) ;死亡组患者血清IL 18水平下降 ,而sFasL水平则升高。患者血清IL 18和sFasL水平与烧伤面积相关 ;患者血清IL 18、sFas和sFasL之间也呈显著正相关 (P <0 0 1)。结论 :患者血清IL 18、sFas和sFasL水平与烧伤严重程度及伤后感染密切相关 ,在烧伤后免疫功能及凋亡调控中可能起一定作用。