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1.
I briefly review spheroids observed in the anterior horns of the spinal cord in amyotrophic lateral sclerosis (ALS). Spheroids are argentophilic bodies more than 20 μm in diameter. Recently, some connections between the proximal axonal swellings including spheroids and the perikarya have been reported in some ALS patients with a short clinical course or mild depletion of anterior horn neurons. Most of the cell bodies directly connected with the axonal swellings appear normal, and spheroids are considered to be one of the hallmarks of the early histological changes in this disorder. Spheroids are strongly positive with anti-phosphorylated neurofilament antibody, and are also positive with calcitonin gene-related peptide and anti-peripherin antibody. Some spheroids are immunostained with anti-synaptophysin antibody and anti-ubiquitin antibody. Spheroids are not immunostained with anti-phosphorylated tau antibody, or high molecular weight microtubule associated proteins. Electron microscopically, spheroids are usually composed of densely packed accumulation of 10 nm neurofilaments with a variety of orientations, plus vesicles, dense bodies and mitochondria. When the swellings of the initial segment is relatively pronounced, the undercoating is obscured and the neurofilaments become interwoven in some parts. In the first internode of the myelinated axons, as the swellings become larger, the neurofilaments lose their parallel orientation and become intermingled. Large accumulation of neurofilaments resembling spheroids in the perikarya of large anterior horn cells suggests that spheroids could be derived not only from the axon including the proximal portion, but also from the perikarya. Structures apparently identical to axonal spheroids are observed at the light and electron microscopic levels in the proximal portion of axons of anterior horn cells in animal models intoxicated with β, β'-iminodipropionitrile (IDPN), or with aluminum, in hereditary canine spinal muscular atrophy (HCSMA). The pathogenetic mechanism is probably associated with an impairment in slow axonal transport which particularly affects the neurofilaments in IDPN and aluminum intoxication. Impairment of slow axonal transport of neurofilaments also plays an important role in the pathogenesis of ALS. The average diameter of even normalappearing initial segment is larger in ALS than in the controls. The perikarya connected with the swollen proximal axons and their dendrites almost always appear normal. These findings suggest that the slow axonal transport of neurofilaments is probably impaired in this portion of the axon at an early stage in ALS as well as animal models for human ALS. However, techniques to analyze slow axonal transport in humans still remain tobe developed. Recently, overexpression of neurofilament subunits in transgenic mice produces a condition resembling ALS. The transgenic model may offer an interesting perspective not only for testing therapeutic strategies but also for investigating in a systematic way the various genetic and environment factors controlling the onset and progression of the disease and might yield new insights on the etiology of ALS.  相似文献   
2.
Female rats consistently show a pattern of differences in defensive behaviors compared to males which parallel the effects of exposure to a nonpainful threat stimulus (cat or cat odor) in the same tests and measures. These indications of greater defensiveness for females are particularly common in situations involving potential, as opposed to actual and present, threat, a factor which probably also reflects ceiling or floor effects in situations involving very intense defensiveness. In addition, pharmacological studies indicate sex differences in the effects of selective serotonin (5-HT) receptor agonists and antagonists on defensive responding. These findings indicate that sex effects must be considered in studies of the pharmacological control of defensive behaviors, and suggest that responsivity to sex effects may be an additional criterion for the suitability of animal models of anxiety.  相似文献   
3.
BACKGROUND/PURPOSE: Laser-induced autofluorescence spectroscopy provides excellent possibilities for medical diagnostics of different tissue pathologies including cancer. However, to create the whole picture of pathological changes, investigators collect spectral information from patients in vivo or they study different tumor models to obtain objective information for fluorescent properties of every kind of healthy and diseased tissue. Therefore, it is very important to find the most appropriate, and close to the human skin, animal samples from the fluorescence point of view, which will allow the extrapolation of the animal data to human spectroscopic diagnostics. METHODS: In the present work, we examined the autofluorescence properties of different animal skin tissues, which are considered as the most common skin models. A nitrogen laser was used as an excitation source. Samples of healthy mouse, chicken and pig skin in vivo and/or ex vivo were studied and were compared with results obtained from investigations of healthy human skin in vivo. RESULTS AND CONCLUSION: Specific features of the recorded spectra are discussed and the possible origin of the obtained fluorescence signals is proposed. Quantitative evaluation of data extrapolation for each skin type is also depicted.  相似文献   
4.
BACKGROUND: The demand for renal replacement therapy (RRT) in England has risen steadily, although from a lower base than many other developed countries. Predicting the future demand for RRT and the impact of factors such as the acceptance rate, transplant supply and patient survival, is required in order to inform the planning of such services. METHODS: A discrete event simulation model estimates the future demand for RRT in England in 2010 for a range of scenarios. The model uses current prevalence and current and projected future acceptance rates, survival rates and the transitions between modalities to predict future patient numbers. National population and mortality data, published literature and data from the UK Renal Registry and UK Transplant, are used to estimate unmet need for RRT, the impact of changing demography and incidence of Type 2 diabetes, patient haemodialysis (HD) survival and transplant supply. RESULTS: By 2010 the predicted prevalence will have increased from about 30,000 in 2000 to between 42 and 51,000 (900-1000 p.m.p.), an average annual growth of 4.5-6%. Changing transplant supply has a small effect on overall numbers but changes the proportion of patients with functioning graft by up to 8%. Even with an optimistic increase in transplant supply (11% p.a. for 5 years), numbers on HD will continue to rise substantially, especially in the elderly. The factors most influencing future patient numbers are the acceptance rate and dialysis survival. CONCLUSION: This model predicts a substantial growth in the RRT population to 2010 to a rate approaching 1000 p.m.p., particularly in the elderly and those on HD, with a steady state not being reached for at least 25 years.  相似文献   
5.
There is now a substantial body of American research evidence demonstrating that early education programmes can have major long term effects right through into adult life. Cost-benefit analysis has enabled the data to be transformed into a compelling case for public financial investment. But insufficient attention has been paid to explaining how a short term preschool programme could have such enduring effects. The effects are best understood by applying a transactional model which shows how processes in the school and community transformed and amplified short term effects into long term outcomes. Adopting a transactional model modifies the messages for policy. The results of evaluations carried out in one society may not apply in another. In some school systems there may be more effective strategies than early education for improving educational prospects.  相似文献   
6.
The visual pursuit test is a method that collects and analyzes the characteristics of pursuit eye movements and examines the function of the eye movement system. This paper analyzes the model parameters of the smooth pursuit eye movement system in order to explore a method for improving the analysis. The input-output relationship of the smooth pursuit system can be expressed by a quasilinear model. We compute the model parameters (gain, phase, spectral purity, cross covariance) by digital signal processing. Eye movement is recorded by electrooculogram. Both eyes are tested individually. The visual target moves at frequencies of 0.2, 0.4, 0.8, 1.2, and 1.6 Hz. Ranges are gain, 1.01 to 0.70; phase, -0.1 ° to -66 °; spectral purity, 0.97 to 0.70; and cross covariance, 0.99 to 0.26. We tested 40 normal subjects as well as patients with ataxia (8), vertigo (18), and ophthalmoplegia (9). The oculomotor system of normal subjects functions as a linear system in the performance of this test at 0.2 to 0.8 Hz. The spectral purity dropped to about 0.70 at 1.6 Hz. The variability of all measures increases greatly at 1.6 Hz, which indicates that this target motion exceeds the tracking ability of many normal subjects and that the oculomotor system of normal subjects functions as a nonlinear system in this condition. Statistical tests show no significant differences between sex, age, and the two eyes. The model parameters tentatively proved effective in clinical application.  相似文献   
7.
Focal full-thickness cartilage lesions of the human medial femoral condyle (MFC) can cause pain and functional impairment. Affected middle-aged patients respond unpredictably to existing treatments and knee arthroplasty may be required, prompting risk of revision. This study assesses the safety of, and biological and functional response to, a metallic resurfacing implant which may delay or obviate the need for traditional arthroplasty. The anatomic contour of the surgically exposed MFC of six adult goats was digitally mapped and an 11 mm diameter full-thickness osteochondral defect was created. An anchor-based Co-Cr resurfacing implant, matching the mapped articular contour, was implanted. Each goat's contralateral unoperated femorotibial joint was used as a control. Postoperative outcome was assessed by lameness examination, radiography, arthroscopy, synoviocentesis, necropsy, and histology up to 26 (n = 3) or 52 (n = 3) weeks. By postoperative week (POW) 4, goats demonstrated normal range of motion, no joint effusion, and only mild lameness in the operated limb. By POW 26 the animals were sound with only occasional very mild lameness. Arthroscopy at POW 14 revealed moderate synovial inflammation and a chondral membrane extending centrally across the implant surface. Radiographs at POWs 14 to 52 implied implant stability in the operated joints, as well as subchondral bone remodeling and mild exostosis formation in the operated and contralateral unoperated joints of some goats. By POW 26, histology revealed new trabecular bone abutting the implant. At POWs 26 and 52 MFC cartilage was metachromatic and intact in the operated and unoperated femorotibial joints. Proximal tibiae of some operated and unoperated limbs demonstrated limited subchondral bone remodeling and foci of articular cartilage fibrillation and thinning. The chondral membrane crossing the prosthesis possessed a metachromatic matrix containing singular and clustered chondrocytes. Our data imply the safety, biocompatibility, and functionality of the implant. Focal articular damage was documented in the operated joints at POWs 26 and 52, but lesions were much reduced over those previously reported in untreated defects. Expanded animal or preclinical human studies are justified.  相似文献   
8.
Profound reductions in cortical acetylcholine levels together with degeneration of cholinergic neurons in the basal forebrain have been reported in patients with Alzheimer's disease. A similar loss of the cholinergic neurons of the basal forebrain and impairment of learning and memory occur in animals injected with a nerve growth factor-diphtheria toxin conjugate, suggesting that this animal model is suitable to analyze cholinergic roles on learning and memory processes, and also the pathogenesis of Alzheimer's disease. In addition, animal models constructed by electrolytic or neurotoxic lesioning of the basal magnocellular nucleus, and models made by transgenetic technology were described.  相似文献   
9.
Summary Changes in regional cerebral blood flow in anaesthetized pigs with an induced focal cerebral contusion were studied before and after two grades of hyperventilation. A reduction in arterial tension of CO2 with 0.70mmHg and a further reduction of 0.55mmHg did not change the CO2 reactivity. Reactivity in both injured and macroscopically normal regions was the same, revealing an average of 39.3% flow change per kPa change in CO2 tension. Regions with low flow after the contusion had an equally big reduction apparently leading to hypoxia because global metabolic rate was unchanged.  相似文献   
10.
Department of Pathological Anatomy, Clinical-Biological Laboratory, and Laboratory of Immunology, Bacteriology, and Clinical Pharmacology, A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR D. S. Sarkisov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 3, pp. 285–287, March, 1991.  相似文献   
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