Functional deficits in phonological working memory in children with intellectual disabilities

Recent studies indicate that children with intellectual disabilities have functional limitations primarily in the phonological loop of working memory (Baddeley, 1986). These findings are indicative of a specific structural deficit. Building on this research, the present study examines whether it is possible to identify specific phonological subfunctions as causal factors in these qualitative deviations from typical development found in children with intellectual disabilities. In a three-group design, specific subfunctions of phonological working memory were examined in students of the same mental age (one group of 15-year-olds with mild intellectual disability [IQ 50-69], one group of 10-year-olds with borderline intellectual disability [IQ 70-84], and one group of 7-year-olds of average intelligence [IQ 85-115]). The automatic activation of the subvocal rehearsal process was operationalized by the word-length effect; the size of the phonological store, by a task involving repetition of nonwords of differing syllable length; and accuracy of processing, by both the phonological similarity effect and the quality of acoustic presentation of the nonword repetition task (distorted vs. undistorted item presentation). The results revealed impairment of the phonological store only in terms of reduced storage capacity, and showed that this deficit increased with length of the item sequences to be remembered. However, this deficit was observed only in children with mild intellectual disability; the performance of children with borderline intellectual disability corresponded with that of a control group of 7-year-olds matched for mental age. The findings are discussed in the context of the two-component model of the phonological loop. They indicate that deficits in storage capacity are associated with deficits in language development and thus seem to be one of the causes of cognitive impairment in individuals with mild intellectual disability.     

Effect of lidoflazine (R 7904) on uptake and release of serotonin by human platelets in vitro

Summary At low concentrations in vitro (starting at 5×10^–8 M), lidoflazine reduces the velocity of serotonin uptake by human platelets suspended in Tyrodealbumin. Inhibition is of a non-competitive type and is not enhanced by prolonged compound incubation.At higher concentrations (starting at 1.6×10^–6 M) lidoflazine causes release of radioactive serotonin from platelets. The extent of release is dependent on concentration, duration of incubation and temperature and is not reduced by calcium chelation or papaverine pre-treatment. Similar but less pronounced effects on uptake and release reactions occur with dipyridamole. The possible mode of action of lidoflazine on platelet storage of serotonin is discussed.     

The nature of storage deficits and state-dependent retrieval under marihuana

To explore the nature of the storage deficit produced by marihuana intoxication and to determine if retrieval is state dependent for this drug, 48 subjects were presented 10–20-word lists before receiving an oral dose of marihuana and another 10 lists following drug administration. Subjects studied half of each set of 10 pre-drug and 10 post-drug lists using an overt fixed-rehearsal procedure and half using their normal covert free-rehearsal procedure. On Day 1 of the experiment an immediate-recall test followed each of the 20 lists presented. The marihuana-induced deficit in immediate-recall performance on Day 1 for free-rehearsal lists was not eliminated when the fixed-rehearsal procedure was used. Thus, marihuana intoxication impaired the storage of information even when overt rehearsal in the drug and no-drug states was equated. Three days later (Day 4) subjects returned, half receiving marihuana (Drug Group) and half receiving placebo (Placebo Group). All subjects were then administered delayed recall, recognition, and order tests on the words presented on Day 1. Delayed recall performance was asymmetrically state dependent, whereas delayed recognition performance was not state dependent.This research was supported by the van Ameringen Foundation and National Institutes of Mental Health grant 21747.The authors thank Caroline Bowker, Claire Darley, Glenn Huntsherger, Saul Kantor, Frances Moore, Patricia Murphy, Peggy Murphy, and Margaret Rosen-bloom for their technical assistance.     

Isolated chromaffin granules maintenance of ATP content during incubation at 31 degrees C

Chromaffin granules incubated at 31°C, lose 30% of their catecholamines and nucleotides in 4 hr. However, in the presence of ATP and Mg²⁺ less than 10% of the catecholamines and nucleotides are released. Apparently the ATP-stimulated uptake of catecholamines prevents both the loss of catecholamines and that of nucleotides.     

Atypical CLN2 with later onset and prolonged course: a neuropathologic study showing different sensitivity of neuronal subpopulations to TPP1 deficiency

This is the first neuropathology report of a male patient (born 1960-died 1975) with an extremely rare, atypical variant of CLN2 that has been diagnosed only in five families so far. The clinical history started during his preschool years with relatively mild motor and psychological difficulties, but with normal intellect and vision. Since age six there were progressive cerebellar and extrapyramidal symptomatology, amaurosis, and mental deterioration. Epileptic seizures were absent. The child died aged 15 years in extreme cachexy. Neuropathology revealed neurolysosomal storage of autofluorescent, curvilinear and subunit c of mitochondrial ATP synthase (SCMAS) rich material. The neuronal storage led to laminar neuronal depopulation in the cerebral cortex and to a practically total eradication of the cerebellar cortical neurons. The other areas of the central nervous system including hippocampus, which are usually heavily affected in classical forms of CLN2, displayed either a lesser degree or absence of neuronal storage, or storage without significant neuronal loss. Transformation of the stored material to the spheroid like perikaryal inclusions was rudimentary. The follow-up, after 30 years, showed heterozygous values of TPP1 (tripeptidylpeptidase 1) activity in the white blood cells of both parents and the sister. DNA analysis of CLN2 gene identified a paternal frequent null mutation c.622C > T (p.Arg208 X) in the 6th exon and a maternal novel mutation c.1439 T > G in exon 12 (p.Val480Gly). TPP1 immunohistochemistry using a specific antibody gave negative results in the brain and other organs. Our report supports the notion that the spectrum of CLN2 phenotypes may be surprisingly broad. The study revealed variable sensitivities in neuronal subpopulations to the metabolic defect which may be responsible for the variant's serious course.     

Ultrastructure of myocardium in the hurler syndrome

Summary Cardiac tissues obtained at post mortem examination of eight patients with the Hurler syndrome, who ranged in age from 5 to 23 years, were examined by histochemical methods and electron microscopy. Extensive myocardiocytic vacuolization and increased interstitial fibrous tissue were noted by light microscopy in all hearts. The cytoplasmic (perinuclear) vacuoles contained Luxol-fast-blue-positive substance. At the ultrastructural level, abnormal cytoplasmic organelles were present within the myocardiocytes in all patients. These organelles were of three types: zebra bodies (ZB), membranous cytoplasmic bodies (MCB) and granulomembranous bodies (GMB). As ZB and MCB are believed to represent the morphological counterpart of accumulated gangliosides, these substances rather than glycosaminoglycans appear to be stored within myocardiocytes of patients with the Hurler syndrome. The accumulation of gangliosides and the consequent damage to the myocardial substratum probably contributes to the clinically evident cardiac disease, so often observed in the patients with this disorder.Supported in part by grants-in-aid T.3-11 and 3-3 from the Ontario Heart Foundation, No. 766 from the Ontario Mental Health Foundation, Toronto, and a Special Research Fund, University Hospital, London, Ontario, CanadaPresented in part at the Annual Meeting of the Canadian Association of Pathologists, Quebec City, Quebec, Canada, June 16–20, 1979Recipient of a Medical Research Council of Canada Fellowship, 1978–1980     

Physico-chemical characterisation of PLGA nanoparticles after freeze-drying and storage

Nanoparticles represent promising carriers for controlled drug delivery. Particle size and size distribution of the particles are important parameters for the in vivo behaviour after intravenous injection and have to be characterised precisely. In the present study, the influence of lyophilisation on the storage stability of poly(d,l lactic-co-glycolic acid) (PLGA) nanoparticles, formulated with several cryoprotective agents, was evaluated. Nanoparticles were prepared by a high pressure solvent evaporation method and freeze-dried in the presence of 1%, 2%, and 3% (m/v) sucrose, trehalose, and mannitol, respectively. Additionally, to all samples containing 3% of the excipients, l-arginine hydrochloride was added in concentrations of 2.1% or 8.4% (m/V). Dynamic light scattering (DLS), analytical ultracentrifugation and transmission electron microscopy (TEM) were used for particle characterisation before and after freeze-drying and subsequent reconstitution. In addition, glass transition temperatures were determined by differential scanning calorimetry (DSC), and the residual moisture of the lyophilisates was analysed by Karl Fischer titration. It was demonstrated that 1% sucrose or 2% trehalose were suitable to maintain particle integrity after reconstitution of lyophilised PLGA nanoparticles. The storage stability study over 3 months showed notable changes in mean particle size, size distribution, and residual moisture content, depending on the composition of the formulation.     

基于IP的医院信息系统存储策略

分析了医院存储系统特点，在比较现有各种存储技术的基础上，提出了基于IP的网络存储策略。     

The 5-HT 1A receptor antagonist WAY 100635 improves rats performance in different models of amnesia evaluated by the object recognition task

The effects of the 5-HT(1A) receptor antagonist WAY 100635 on recognition memory were investigated in two different amnestic models in the rat by using the object recognition task. WAY 100635 at 1 mg/kg, but not at 0.3 mg/kg, counteracted scopolamine-induced performance deficits in the acquisition version of this behavioral paradigm. At the same dose, WAY 100635 antagonized extinction of recognition memory in the normal rat, suggesting that it affected acquisition, storage and retrieval of information. These results support and extend prior findings that interactions between the serotonergic and cholinergic systems are relevant to cognition and indicate that WAY 100635 modulates different aspects of recognition memory.     

储存温度与时间对血清标本生化检验结果的影响

目的探讨血清标本在不同温度与时间下储存对生化检验结果的影响。方法将血清标本分不密封、密封分别放置35、20、4℃的环境中保存1、2．4h后，检测150例病人11项生化指标ALT、AST、CK、TB、TP、Alb、TC、BUN、UA、Glu、P的值，并与放置前测定的值进行比较。结果血清密封放置在各个温度下2h后无显著性改变；而无密封放置20℃4h后有9项结果增高，有显著性差异（p〈0．05）。结论做好分析前标本质量控制，血清标本应及时检测，如不能及时检测应将分离的血清放置于冰箱4℃密封保存。