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The experience with the treatment of malignant histiocytosis has been disappointing. Despite modest treatment success with a combination of cyclophosphamide, Adriamycin (doxorubicin), vincristine and prednisone, the overall prognosis remains poor. There are only a few reports of prolonged complete remissions in pediatric patients. The following report describes two children who have had long-term remission with an aggressive combination chemotherapy program that included intrathecal prophylaxis. The chemotherapeutic regimen described merits further evaluation in a larger number of patients. 相似文献
104.
High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain. 总被引:12,自引:0,他引:12
Michael T Lin David K Simon Colette H Ahn Lauren M Kim M Flint Beal 《Human molecular genetics》2002,11(2):133-145
The mitochondrial theory of aging proposes that mitochondrial DNA (mtDNA) accumulates mutations with age, and that these mutations contribute to physiological decline in aging and degenerative diseases. Although a great deal of indirect evidence supports this hypothesis, the aggregate burden of mtDNA mutations, particularly point mutations, has not been systematically quantified in aging or neurodegenerative disorders. Therefore, we directly assessed the aggregate burden of brain mtDNA point mutations in 17 subjects with Alzheimer's disease (AD), 10 elderly control subjects and 14 younger control subjects, using a PCR-cloning-sequencing strategy. We found that brain mtDNA from elderly subjects had a higher aggregate burden of mutations than brain mtDNA from younger subjects. The average aggregate mutational burden in elderly subjects was 2 x 10(-4) mutations/bp. The bulk of these mutations were individually rare point mutations, 60% of which changed an amino acid. Control experiments ensure that these results were not due to artifacts arising from PCR error, mistaken identification of nuclear pseudogenes or ex vivo oxidation. Cytochrome oxidase activity correlated negatively with increasing mutational burden. These findings significantly bolster the mitochondrial theory of aging. 相似文献
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Heat shock protein hsp72 induction in cortical and striatal astrocytes and neurons following infarction 总被引:3,自引:0,他引:3
F R Sharp D Lowenstein R Simon K Hisanaga 《Journal of cerebral blood flow and metabolism》1991,11(4):621-627
Transient global and transient focal ischemia induced the 72 kDa heat shock protein (hsp72) in neurons in cortex, striatum, and other regions known to be injured during transient ischemia. A novel finding was the induction of hsp72 in islands (cylinders in three dimensions) of cells composed of astrocytes around the perimeter and neurons in the interior. Since histology showed pale staining in these regions, it is proposed that these islands represent areas of focal infarction in the distribution of small cortical and lenticulostriate arteries. Although the factors responsible for hsp72 induction during ischemia and infarction are unknown, these results suggest differences in mechanisms of hsp72 induction in astrocytes compared to neurons. 相似文献
107.
Delineating the sites and progression of in vivo atrophy in multiple system atrophy using fluid-registered MRI. 总被引:1,自引:0,他引:1
Jonathan M Schott Jessica E Simon Nick C Fox Andrew P King M Nadeem Khan Lisa Cipolotti Dominic C Paviour John M Stevens Martin N Rossor 《Movement disorders》2003,18(8):955-958
We describe the pattern and progression of atrophy delineated using fluid registration of serial magnetic resonance imaging scans in a case of multiple system atrophy (MSA). The in vivo findings were consistent with those found at postmortem, including significant supratentorial atrophy concurrent with an unusual degree of cognitive impairment for MSA. 相似文献
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