Annals of neurology
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Annals of neurology · Dec 2001
Clinical TrialEffect of therapeutic ionizing radiation on the human brain.
We test a hypothesis that fractionated radiation therapy within a therapeutic dose range is associated with a dose-related change in normal brain, detectable by quantitative magnetic resonance imaging. A total of 33 patients were examined by quantitative magnetic resonance imaging to measure brain tissue spin-lattice relaxation time (T1) before treatment, and at various times during and after radiation therapy. A T1 map was generated at each time point, and radiation therapy isodose contours were superimposed on the corresponding segmented T1 map. ⋯ Human white matter T1 is not sensitive to radiation therapy of less than 20 Gy, and gray matter T1 is unchanged over the dose range used to treat human brain tumor. The reduction of gray matter T1 near the tumor could result from compression of cortical parenchyma near the growing tumor mass, or from tumor cell invasion directly into the parenchyma. If brain T1 is a surrogate for radiation effect, reducing the volume of normal white matter receiving more than 20 Gy could be an important treatment planning goal.
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Annals of neurology · Oct 2001
Monocyte activation and differentiation augment human endogenous retrovirus expression: implications for inflammatory brain diseases.
Human endogenous retroviruses (HERVs) have been implicated as causative agents in diseases characterized by inflammation and macrophage activation, such as multiple sclerosis. Because monocyte activation and differentiation influence retroviral transcription and replication, we investigated the contribution of these processes to the expression of four HERV families (HERV-W, HERV-K, HERV-E, and HERV-H) in human monocytes, and autopsied brain tissue from patients with brain diseases associated with increased macrophage activity. Reverse transcriptase-polymerase chain reaction analysis of primary macrophages and U937 monocytoid cells stimulated with phorbol-12-myristate-13-acetate or lipopolysaccharide revealed three- to ninefold increases in HERV-W, HERV-K, and HERV-H RNA levels. ⋯ Compared with controls, HERV-W and HERV-K expression was increased in brain tissue from patients with multiple sclerosis or human immunodeficiency virus infection or AIDS, with concomitant elevated tumor necrosis factor-alpha levels. Similarly, elevated HERV-W levels were detected in patients with Alzheimer's dementia only when tumor necrosis factor-alpha expression was also evident (2 of 6 cases). The detection of several HERVs in inflammatory brain diseases and the capacity to augment HERV expression in monocytes with compounds that influence cellular activity suggest that increased expression of these viruses is a consequence of increased immune activity rather than causative of distinct diseases.
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We report 143 Australian and North American cases of primary nemaline myopathy. As classified by the European Neuromuscular Centre guidelines, 23 patients had severe congenital, 29 intermediate congenital, 66 typical congenital, 19 childhood-onset, and 6 adult-onset nemaline myopathy. Inheritance was autosomal recessive in 29 patients, autosomal dominant in 41, sporadic in 72, and indeterminate in 1. ⋯ Arthrogryposis, neonatal respiratory failure, and failure to achieve early motor milestones were associated with early mortality. Morbidity from respiratory tract infections and feeding difficulties frequently diminished with increasing age. Aggressive early management is warranted in most cases of congenital nemaline myopathy.