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91.
During slow wave sleep and consummatory behaviors, electroencephalographic recordings from the rodent hippocampus reveal large amplitude potentials called sharp waves. The sharp waves originate from the CA3 circuitry and their generation is correlated with coherent discharges of CA3 pyramidal neurons and dependent on activities mediated by AMPA glutamate receptors. To model sharp waves in a relatively large hippocampal circuitry in vitro, we developed thick (1 mm) mouse hippocampal slices by separating the dentate gyrus from the CA2/CA1 areas while keeping the functional dentate gyrus-CA3-CA1 connections. We found that large amplitude (0.3-3 mV) sharp wave-like field potentials occurred spontaneously in the thick slices without extra ionic or pharmacological manipulation and they resemble closely electroencephalographic sharp waves with respect to waveform, regional initiation, pharmacological manipulations, and intracellular correlates. Through measuring tissue O2, K+, and synaptic and single cell activities, we verified that the sharp wave-like potentials are not a consequence of anoxia, nonspecific elevation of extracellular K+ and dissection-related tissue damage. Our data suggest that a subtle but crucial increase in the CA3 glutamatergic activity effectively recruits a population of neurons thus responsible for the generation of the sharp wave-like spontaneous field potentials in isolated hippocampal circuitry. 相似文献
92.
Deconditioning is a complex process of physiological change following a period of inactivity, bedrest or sedentary lifestyle. It results in functional losses in such areas as mental status, degree of continence and ability to accomplish activities of daily living. It is frequently associated with hospitalization in the elderly. The most predictable effects of deconditioning are seen in the musculoskeletal system and include diminished muscle mass, decreases of muscle strength by two to five percent per day, muscle shortening, changes in periarticular and cartilaginous joint structure and marked loss of leg strength that seriously limit mobility. The decline in muscle mass and strength has been linked to falls, functional decline, increased frailty and immobility. The authors describe a three-pronged strategy to combat deconditioning that includes a model of care appropriate to the growing population of elderly clients, the creation of an "elder-friendly" hospital environment and an exercise program. 相似文献
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Aseffa A Brennan P Dockrell H Gillis T Hussain R Oskam L Richardus JH;Ideal Consortium 《Leprosy review》2005,76(2):147-159
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Toxicity and Cerebrospinal Fluid Levels of Carboplatin Chronically Infused into the Brainstem of a Primate 总被引:2,自引:0,他引:2
Strege RJ Liu YJ Kiely A Johnson RM Gillis EM Storm P Carson BS Jallo GI Guarnieri M 《Journal of neuro-oncology》2004,67(3):327-334
PURPOSE: Carboplatin was infused into the brainstem of cynomolgus monkeys to investigate neurotoxicity and systemic exposures following chronic local delivery. METHODS: Infusions at 0.42 microl/h were intended to deliver 0.025 (n = 2), 0.075 (n = 3), 0.25 (n = 5), and 0.75 (n = 3) mg/kg by day 30. Laboratory tests, radiographic measurements, and clinical observations were used to monitor toxicity. Blood and cerebrospinal fluid (CSF) were sampled for platinum. RESULTS: Lethargy and ataxia were observed after week 4 in the monkeys given 0.075 mg/kg, and week 2 in the monkeys given 0.25 mg/kg when the infused doses were approximately 250 and 400 microg, respectively. Rapidly progressive neurotoxicity with the 0.75 mg/kg dose required termination of the infusions at days 4-10. Hematology and chemistry values were unremarkable in all groups. Blood levels of platinum remained undetectable in 0.025 and 0.075 mg/kg dose groups. Levels in the 0.25 mg/kg group were 3.1 +/- 0.6 microg/l at 2 weeks and 5.2 +/- 0.8 microg/l at 1 month. The CSF platinum levels varied. Animals in the 0.25 mg/kg group had higher CSF levels at 2 weeks (avg. 65 microg/l, range 36-89) compared to their 1 month value (avg. 60 microg/l, range 7-170), despite the constant infusion. CONCLUSION: Carboplatin can be chronically infused into monkey brainstems. Neurotoxicity is the predominant side effect and is dose-dependent. Pharmacokinetics of local and systemic delivery are different for carboplatin. Further studies are needed to monitor toxicity at higher flow rates and to investigate drug binding to abnormal central nervous system (CNS) tissues. 相似文献
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Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system 总被引:6,自引:0,他引:6
Squire S Raymackers JM Vandebrouck C Potter A Tinsley J Fisher R Gillis JM Davies KE 《Human molecular genetics》2002,11(26):3333-3344
Duchenne muscular dystrophy results from the absence of dystrophin, a cytoskeletal protein. Previously, we have shown in a transgenic mouse model of the disease (mdx) that high levels of expression of the dystrophin-related protein, utrophin can prevent pathology. We developed a new transgenic mouse model where muscle specific utrophin expression was conditioned by addition of tetracycline in water. Transgene expression was turned on at different time points: in utero, at birth, 10 and 30 days after birth. We obtained moderate levels of expression, variable from fibre to fibre (mosaicism) but sufficient to induce a correct localization of the dystro-sarcoglycan complex. Histology revealed a reduction of necrotic foci and of the percentage of centronucleated fibres, which remained still largely above the normal level. Isometric force was not improved but the resistance to eccentric contractions was significantly stronger. When utrophin expression was activated 30 days after birth, improvements were marginal, suggesting that the age at which utrophin therapy is initiated could be an important factor. Our results also provide an unexpected insight into the pathogenesis of the dystrophinopathies. We observed a complete normalization of the characteristics of the mechano-sensitive/voltage-independent Ca(2+) channels (occurrence, open probabilities and Ca(2+) currents), while the classical markers of dystrophy were still abnormal. These observations question the role of increased Ca(2+) channel activity in initiating the dystrophic process. The new model shows that utrophin therapy, initiated after birth, can be effective, but the extent of correction of the various symptoms of dystrophinopathy critically depends on the amount of utrophin expressed. 相似文献
100.
Hemifacial microsomia in two patients further supporting chromosomal mosaicism as a causative factor
de Ravel TJ Legius E Brems H Van Hoestenberghe R Gillis PH Fryns JP 《Clinical dysmorphology》2001,10(4):263-267
We report two cases with hemifacial microsomia with body asymmetry associated with mosaic trisomies. The child with mosaic trisomy 9 had skin pigmentary changes. In the boy with mosaic trisomy 22, the extra chromosome 22 originated from a maternal meiosis I error. 相似文献