Widespread Horizontal Connections Arising from Layer 5/6 Border Inverted Cells in Rabbit Visual Cortex

Herein we describe the inverted cells [defined as those projection neurons having a major dendritic shaft abpially oriented (Bueno-López et al., Eur. J. Neurosci. , 3, 415, 1991)] originating a unique set of cortical connections characterized by extraordinarily widespread horizontal distribution. Single and multiple injections of wheatgerm agglutinin - horseradish peroxidase were made in areas 17 and 18 and the resulting retrograde labelling in the cortex was analysed. The findings were assessed in independent control experiments in which Fluoro-Gold was used as retrograde tracer. Following single injections in area 17 several separate patches of labelled cells comprising layers 2–6 were consistently found in area 18. In addition to these associational cells a number of labelled cells appeared at the layer 5/6 border but were distributed over most of the tangential extent of the visual occipital cortex. This widespread pattern was particularly striking in brains after multiple injections. In these brains a conspicuous band of labelled cells at the 5/6 border radiated from the injection sites, making up an apparently continuous horizontal sheet that intersected the striate - extrastriate boundary and merged with the patches of labelled cells in area 18 and beyond. Most of the cells in the 5/6 border band were inverted cells (82%; n = 2081). Injections in area 18 failed to produce such a widespread set of labelled cells in area 17. The functional significance of these connections furnished by the 5/6 border inverted cells remains to be determined, but their distribution would allow for convergent/divergent binding interactions both intra-areally (within area 17) and inter-areally (from area 18 to area 17).     

Increased senile plaques without microglia in Alzheimer's disease

Summary To clarify the association of microglia with senile plaques, the brains from 13 patients with Alzheimer's disease (AD) and 23 nondemented aged controls were investigated immunohistochemically by a double-labeling method using anti--protein antiserum and anti-ferritin antibody, which is a recently reported microglia marker. In addition, a quantitative analysis was performed. The senile plaques which appeared initially in the nondemented aged controls consisted of a diffuse type without any amyloid cores and these were found in the group aged 50–59 years. The great majority of them were found to contain no ferritin-positive microglia. The number and proportion (percentage) of microglia-containing diffuse plaques increased with age. Classical and compact plaques began to appear in the brains of the group aged 70 years and over, and practically all of them contained microglia. These results suggest that microglia are not associated with initial plaque formation, but correlate with amyloid core formation. In AD, the most prominent feature was that the diffuse plaques, which contained either no or only a few ferritin-positive microglia, increased markedly.Supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan     

Aktivierungsverhalten bei sensumotorischer regeltätigkeit in abhängigkeit von der leistung

Zusammenfassung Mit 40 Versuchspersonen wurde Kompensationstracking durchgeführt. Anhand des Leistungsparameters Regelfehler wurden 2 Gruppen gebildet, bei denen untersucht wurde, ob sie sich im Aktivierungsverhalten unterscheiden. Es wurde gefunden, daß die Herzfrequenz- und Atemfrequenzsteigerungen in allen Versuchsabschnitten bei der Gruppe mit guter Trackingleistung signifikant höher waren. Die Streuung der Herzfrequenz war bei der schlechten Gruppe geringer.Die Aktivierungsvariablen Herz- und Atemfrequenz unterscheiden sich am deutlichsten in der jeweils ersten Belastungsminute der Versuchsabschnitte, dabei spiegelt die Herzfrequenz die Aufgabenschwierigkeit besser wider als die Atemfrequenz.Die Untersuchung der Korrelation zwischen dem Leistungsparameter Regelfehler und Herzfrequenzanstieg ergibt bei der Gruppe mit schlechterer Trackingleistung immer negative Werte für r, die in 3 Belastungsabschnitten signifikant sind. Bei der Gruppe mit guter Trackingleistung besteht eine positive Korrelation zwischen Herzfrequenzanstieg und Regelfehler bei geringerer statistischer Sicherheit.Die Ergebnisse werden diskutiert und Schlußfolgerungen für die psychophysiologische Eignungsbeurteilung werden abgeleitet.     

4''-氧代乙酸-7-羟乙氧基-葛根黄豆苷元的小鼠体内分布研究

目的：制备合成了葛根4’-氧代乙酸-7-羟乙氧基-黄豆苷元(DZ18),研究DZ18在小鼠体内的分布。方法：采用HPLC法研究了DZ18静注后小鼠体内的脏器分布规律．对DZ18的血浆蛋白结合率进行了考察。结果：DZ18在心、脑、肝中浓度比较高，DZ18的血浆蛋白结含率随药物浓度的增加而减少。结论：该药主要分布在心、脑等器官，有利于发挥其治疗心脑血管疾病的作用。     

己酮可可碱对2,4,6-三硝基苯磺酸肠炎模型的影响

目的 :观察己酮可可碱 (PTX)对 2 ,4 ,6 三硝基苯磺酸 (TNBS)肠炎模型影响。方法 :通过直肠给予雄性BALB/c小鼠TNBS诱导结肠炎 ,应用PTX对其进行治疗 ,6d后收集结肠标本评价结肠炎症程度 ;采用半定量RT PCR检测肠黏膜IL 18mRNA表达 ,采用免疫组织化学染色显示IL 18阳性细胞。结果 :直肠内给予BALB/c小鼠TNBS后可造成小鼠结肠炎性改变 ;PTX治疗可使小鼠疾病活动指数、结肠重量和炎症指数均显著下降 (P <0 .0 5 ) ,结肠IL 18mRNA和肠黏膜固有层表达IL 18细胞数显著下降 (P <0 .0 5 )。结论 :PTX治疗可使TNBS肠炎模型小鼠肠黏膜局部IL 18表达显著下降 ,肠炎得以减轻。     

Synthesis and evaluation of 5,7‐dichloro‐4‐(3‐{4‐[4‐(2‐[18F]fluoroethyl)‐piperazin‐1‐yl]‐phenyl}‐ureido)‐1,2,3,4‐tetrahydroquinoline‐2‐carboxylic acid as a potential NMDA ligand to study glutamatergic neurotransmission in vivo

The neurotransmitter glutamate is thought to be crucially involved in a huge number of neurological and psychiatric disorders, such as Morbus Parkinson, Alzheimer's disease and schizophrenia. Aiming at an improved diagnostic tool for PET a new [¹⁸F]fluorine labelled NMDA receptor ligand was developed that may potentially allow the in vivo visualization of glutama‐tergic neurotransmission. The ¹⁹F‐analogue trans‐5,7‐dichloro‐4‐(3‐{4‐[4‐(2‐fluoroethyl)‐piperazin‐1‐yl]‐phenyl}‐ureido)‐1,2,3,4‐tetrahydro quinoline‐2‐carboxylic acid was synthesised to determine the binding affinity, lipophilicity and biodistribution of the ligand. This substance exhibits a K_i of 12 nM for the glycine binding site using [³H]MDL‐105,519 assays on pig cortical membranes. A logD of 1.3 was determined for this compound according to the OECD guidelines employing the HPLC method. Radiosynthesis of this ligand was achieved by labelling the precursor trans‐5,7‐dichloro‐4‐[3‐(4‐piperazin‐1‐yl‐phenyl)‐ureido]‐1,2,3,4‐tetrahydroquinoline‐2‐carboxylic acid methyl ester with 2‐[¹⁸F]fluoroethyltosylate and subsequent cleaving of the methyl ester moiety, resulting in an overall decay corrected yield of 35% of the final product trans‐5,7‐dichloro‐4‐(3‐{4‐[4‐(2‐[¹⁸F]fluoroethyl)‐piperazin‐1‐yl]‐phenyl}‐ureido)‐1,2,3,4‐tetrahydroquinoline‐2‐carboxylic acid. The biodistribution kinetics of this compound were determined with Sprague Dawley rats ex vivo for brain, liver, kidney, and bone. The ligand showed a maximum brain uptake 30 min.p.i. of about 0.1% ID/g. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of [18F]‐labeled adenosine analogues as potential PET imaging agents

The syntheses of adenosine analogues, 2′‐deoxy‐2′‐[¹⁸F]fluoro‐9‐β‐D ‐arabinofuranosyladenine ([¹⁸F]‐FAA) and 3′‐deoxy‐3′‐[¹⁸F]fluoro‐9‐β‐D ‐xylofuranosyladenine ([¹⁸F]‐FXA) are reported. Adenosine ( 1 ) was converted to its methoxytrityl derivatives 2 and 3 as a mixture. After separation, these derivatives were converted to their respective triflates 4 and 5 . Each triflate was reacted with tetrabutylammonium[¹⁸F]fluoride to produce 6b or 7b , which by acidic hydrolysis yielded compounds 8b and 9b . Crude preparations were purified by HPLC to obtain the desired pure products. The radiochemical yields were 10‐18% decay corrected (d. c.) for 8b and 30‐40% (d. c.) for 9b in 4 and 3 runs, respectively. Radiochemical purity was >99% and specific activity was >74 GBq/μmol at the end of synthesis (EOS). The synthesis time was 90‐95 min from the end of bombardment (EOB). Copyright © 2003 John Wiley & Sons, Ltd.     

Preparation of fluorine‐18‐labelled fluoromisonidazole using two different synthesis methods

¹⁸F‐labelled fluoromisonidazole [1H‐1‐(3‐[¹⁸F]fluoro‐2‐hydroxypropyl)‐2‐nitroimida‐zole; ([¹⁸F]FMISO)] is used as an in vivo marker of hypoxic cells in tumours and ischaemic areas of the heart and the brain. The compound plays an important role in evaluating the oxygenation status in tumours during radiotherapy. In this paper, we report experiments carried out in our laboratory in synthesizing [¹⁸F]FMISO using two different methods. The first method (I) for the [¹⁸F]FMISO synthesis was the fluorination of (2R)‐(?)‐glycidyl tosylate to [¹⁸F]epifluorohydrin. The subsequent nucleophilic ring opening, achieved with 2‐nitroimidazole, leads to labelled FMISO. The second method (II) was the fluorination of the protected precursor 1‐(2′‐nitro‐1′‐imidazolyl)‐2‐O‐tetrahydropyranyl‐3‐O‐toluenesulphonyl‐propanediol, followed by a rapid removal of the protecting group. With the first method, the radiochemical yield was about 10% at the end of the synthesis (EOS), and the radiochemical purity was over 99%. The radiochemical yield in the second method was 21% (EOS) on an average, and the radiochemical purity was over 97%. When an automated commercial synthesis module was used with method II, slightly better and more reproducible yields were achieved. The improvement in the synthesis yield with the automated apparatus will be valuable when working with high activities, and therefore it is under further development. Copyright © 2003 John Wiley & Sons, Ltd.     

Molecular and functional characterization of porcine LFA-1 using monoclonal antibodies to CD11a and CD18

Abstract: We describe in this report the production and characterization of monoclonal antibodies (mAb) to the swine homologues of CD11a and CD18 antigens, and their use for phenotypic and functional analysis of porcine leukocytes. Monoclonal antibodies BL1H8 and BL2F1 precipitated two bands of approximately 170 and 95 kDa, whereas mAb BA3H2 brought down three bands of 170, 155 and 95 kDa, from alveolar macrophage lysates. Clearance of macrophage lysates with mAbs BL1H8 and BL2F1 resulted in complete removal of the 170-kDa band. The cell distribution of the molecules recognized by these mAbs was similar to that of human LFA-1. It was found on all leukocytes, although its expression varied among the different leukocyte subpopulations, with monocytes, granulocytes and a subset of CD8⁺ cells expressing the highest levels. Cross-blocking studies showed that these antibodies recognize different epitopes on porcine LFA-1. Both anti-LFA-1 mAbs strongly inhibited the mitogenic response of PBMC to ConA, whereas the anti-CD18 mAb had no effect. These anti-LFA-1 mAbs also inhibited the mixed lymphocyte reaction (MLR) and the NK cell-mediated lysis of K-562 cells.     

Subependymoma of the septum pellucidum: Characterization by PET

We report the evaluation of a subependymoma of the septum pellucidum by positron emission tomography (PET) with analysis of ₁₈F-fluorodeoxyglucose (FDG)kinetics. The tumor showed exceedingly low rates of glucose metabolism (rCMRG1) and kinetic constants (K1, K2, and K3). This hypometabolism indicates low cellular density and slow growth.