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51.
Stein TP; Oram-Smith JC; Leskiw MJ; Wallace HW; Long LC; Leonard JM 《The American journal of physiology》1976,230(5):1321-1325
52.
53.
Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases 总被引:5,自引:2,他引:5
Huang JQ; Trasler JM; Igdoura S; Michaud J; Hanal N; Gravel RA 《Human molecular genetics》1997,6(11):1879-1885
Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative
diseases resulting from the inability to catabolize GM2 ganglioside by
beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit
(Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B
(beta beta homodimer) is also defective in Sandhoff disease. We previously
developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs)
mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff)
mice succumb to a profound neurodegenerative disease by 4-6 months of age.
Here we find that neuron death in Hexb-/- mice is associated with apoptosis
occurring throughout the CNS, while Hexa-/- mice were minimally involved at
the same age. Studies of autopsy samples of brain and spinal cord from
human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances,
in keeping with the severe expression of both diseases. We suggest that
neuron death is caused by unscheduled apoptosis, implicating accumulated
GM2 ganglioside or a derivative in triggering of the apoptotic cascade.
相似文献
54.
P S Bass A F Drake Y Wang J H Thomas D R Davies 《Laboratory investigation; a journal of technical methods and pathology》1990,62(2):185-188
The molecular charge on bovine serum albumin (BSA) was modified by substituting carboxyl groups on the protein with ethylenediamine, thereby producing a highly cationic derivative with a pI of 9.3 to 9.5. Gel-filtration studies showed that the molecular weight of BSA was not significantly altered after cationization. When the cationized BSA was administered to rabbits using a chronic serum sickness schedule of injections, the animals developed a membranous glomerulopathy similar to the human disease, except that approximately one-third of the animals also showed focal and segmental endocapillary proliferation. Comparison of the circular dichroism spectra of native and cationized BSA showed that the substitution of the carboxyl groups resulted in a 50% reduction in the alpha-helical content of the native molecule. This conformational change should be considered as a possible determinant of the different immune response and immunopathology associated with the cationized molecule compared with native BSA. 相似文献
55.
56.
R L Drake 《The Anatomical record》1988,220(3):300-304
Insulin treatment of diabetic rats fed a high-carbohydrate, fat-free diet produces a dramatic accumulation of hepatic lipids. However, this increase in hepatic lipids may only be a response to injections of exceptionally high doses of insulin. This study addresses this possibility. Alloxan-diabetic rats, fed a high-carbohydrate, fat-free diet, were given insulin every 12 h for 60 h at the following dosages: 1/2 unit each, 1 unit each, 2 units each, and 4 units each of regular and NPH insulins. At the end of the treatment period, liver samples were collected and used for morphological and biochemical analyses. Histologic examination revealed hepatic lipid accumulations at all insulin doses; the amount of lipid increased until maximal levels were reached at an insulin dosage of 1 + 1, which was maintained at doses of 2 + 2 and 4 + 4. Thus, hepatic lipid accumulation occurs regardless of the dosage of insulin administered to the diabetic animal. It is not simply an abnormal cellular response to excessive hormone levels. Similarly, the activity of the hepatic lipogenic enzyme, malic enzyme, increased at initial insulin dosages and reached maximal levels at 2 + 2. However, in contrast to lipid accumulation, enzyme activity decreased at the final insulin dosage of 4 + 4. Thus, there appears to be a direct relationship between increasing insulin levels and malic enzyme activity until an optimal insulin concentration is reached. After this point, excessive insulin levels do inhibit malic enzyme activity. 相似文献
57.
From 1990 through 1994, we fortuitously isolated Histoplasma capsulatum from six patients with AIDS whose specimens of blood were processed by the BACTEC system using Middlebrook broth selective for acid-fast bacilli (13A medium). Growth indices became positive after an average of 17 days of incubation (range, 11 to 20 days). No acid-fast bacilli were seen, but small budding yeasts characteristic of H. capsulatum were present. 相似文献
58.
59.
Dennis M Edelstein K Copeland K Frederick JA Francis DJ Hetherington R Blaser SE Kramer LA Drake JM Brandt ME Fletcher JM 《Neuropsychology》2005,19(4):456-465
Inhibition of return (IOR) refers to an increase in time to react to a target in a previously attended location. Children with spina bifida meningomyelocele (SBM) and hydrocephalus have congenital dysmorphology of the midbrain, a brain region associated with the control of covert orienting in general and with IOR in particular. The authors studied exogenously cued covert orienting in 8- to 19-year-old children and adolescents (84 with SBM and 37 age-matched, typically developing controls). The exogenous cue was a luminance change in a peripheral box that was 50% valid for the upcoming target location. Compared with controls, children with SBM showed attenuated IOR in the vertical plane, a deficit that was associated with midbrain dysmorphology in the form of tectal beaking but not with posterior brain volume loss. The data add to the emerging evidence for SBM deficits in attentional orienting to salient information. 相似文献
60.
Visual and auditory evoked potentials in migraine 总被引:2,自引:0,他引:2
M E Drake A Pakalnis S A Hietter H Padamadan 《Electromyography and clinical neurophysiology》1990,30(2):77-81
We recorded visual (VEP) and brainstem auditory (BAEP) evoked potentials in 50 patients with clinically diagnosed common migraine attended by visual obscuration or sensory symptoms but no neurologic deficit. VEPs were recorded from Oz, 01, and 02 referenced to Fz, with replication of 200 repetitions of 1.88 per second checkerboard stimuli subtending a 56 minute retinal arc. Analysis time was 250 ms., and filter band pass was 1-250 Hz. BAEPs utilized rarefaction stimulation at 70 dB SL, with 150-3,000 Hz filter band pass and 10 ms. analysis time. Two thousand averages were recorded and replicated from Cz-A1 and Cz-A2. VEP N1, P1 and N2 latencies were longer in migraine patients than in controls, and VEP amplitudes were minimally greater. No significant differences were found between patients and controls, however. BAEP I-V and III-V interpeak latencies were significantly prolonged in migraine patients, and the degree of prolongation was greater on the left. Neither VEPs nor BAEPs exceeded clinical norms in migraine patients. VEPs and BAEPs are likely to add little to the clinical assessment of headache patients. BAEP differences may indicate dysfunction of brainstem centers, possibly related to endorphin or serotonin neurotransmission, and possibly related to the pathogenesis of migraine. The left sided asymmetry has been described previously and is of uncertain significance, but may also support a central mechanism for migraine. 相似文献