Journal of neuropathology and experimental neurology
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J. Neuropathol. Exp. Neurol. · Sep 2005
Comparative StudyInhibition of type 1 diabetic hyperalgesia in streptozotocin-induced Wistar versus spontaneous gene-prone BB/Worchester rats: efficacy of a selective bradykinin B1 receptor antagonist.
Insulin-dependent type 1 diabetes (T1D) is linked to a series of complications, including painful diabetic neuropathy (PDN). Several neurovascular systems are activated in T1D, including the inducible bradykinin (BK) B1 receptor (BKB1-R) subtype. We assessed and compared the efficacy profile of a selective BKB1-R antagonist on hyperalgesia in 2 models of T1D: streptozotocin (STZ) chemically induced diabetic Wistar rats and spontaneous BioBreeding/Worchester diabetic-prone (BB/Wor-DP) rats. ⋯ BB/Wor-DP rats also developed hyperalgesia over time that preceded hyperglycemia, starting at the age of 6 weeks (9% decrease in the hot plate reaction time) and stabilizing over the age of 16 to 24 weeks to a maximum (60% decrease in the hot plate reaction time). Single, acute subcutaneous administration of the selective BKB1-R antagonist induced significant time- and dose-dependent attenuation of hyperalgesia in both STZ diabetic and BB/Wor-DP rats. Thus, selective antagonism of the inducible BKB1-R subtype may constitute a novel and potential therapeutic approach for the treatment of PDN.
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J. Neuropathol. Exp. Neurol. · May 2005
Comparative StudyThe p15(INK4b)/p16(INK4a)/RB1 pathway is frequently deregulated in human pituitary adenomas.
Pituitary adenomas are common benign intracranial neoplasms. However, their tumorigenesis is not yet clearly defined. Inactivation of genes involved in the negative cell-cycle regulatory p15(INK4b) - p16(INK4a) -cyclin D/CDK4-RB1-mediated pathway (RB1 pathway) is one of the most common and important mechanisms in the growth advantage of tumor cells. ⋯ Thus, the vast majority of the adenomas (38 of 42, 90.5%) displayed alterations of the RB1 pathway. None of the clinicopathologic features, including the proliferation cell index, was significantly correlated with any particular methylation status. Our results suggest that inactivation of the RB1 pathway may play a causal role in pituitary tumorigenesis, with hypermethylation of the p16(INK4a) gene being the most common deregulation, and further provide evidence that RB1 and p16(INK4a) methylations tend to be mutually exclusive but occasionally coincide with p15(INK4b) methylation.
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J. Neuropathol. Exp. Neurol. · Apr 2005
Accreditation council for graduate medical education (ACGME) competencies in neuropathology training.
The Accreditation Council for Graduate Medical Education (ACGME) has defined 6 core competencies for all physicians: patient care; medical knowledge; practice-based learning and improvement; interpersonal and communication skills; professionalism; and systems-based practice. However, the specific wording of the descriptions often assumes that the physician is a clinician rather than a pathologist. Therefore, the American Association of Neuropathologists, Inc. asked its Professional Affairs Committee to examine the core competencies and determine how they relate to training in neuropathology. ⋯ Each of the defined competencies is then followed by possible assessment tools, selected from those recommended in the ACGME's "toolbox." Specific suggestions are given for designing tools that apply to neuropathology. Many of the suggested activities and documentation methods can be combined into efficient, carefully formulated training/evaluation exercises. Different tools may be more applicable in some training programs.
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J. Neuropathol. Exp. Neurol. · Mar 2005
ReviewRecent advances in hereditary spinocerebellar ataxias.
In recent years, molecular genetic research has unraveled a major part of the genetic background of autosomal dominant and recessive spinocerebellar ataxias. These advances have also allowed insight in (some of) the pathophysiologic pathways assumed to be involved in these diseases. For the clinician, the expanding number of genes and genetic loci in these diseases and the enormous clinical heterogeneity of specific ataxia subtypes complicate management of ataxia patients. In this review, the clinical and neuropathologic features of the recently identified spinocerebellar ataxias are described, and the various molecular mechanisms that have been demonstrated to be involved in these disorders are discussed.
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J. Neuropathol. Exp. Neurol. · Mar 2005
Comparative StudyCorticospinal regeneration into lumbar grey matter correlates with locomotor recovery after complete spinal cord transection and repair with peripheral nerve grafts, fibroblast growth factor 1, fibrin glue, and spinal fusion.
Knowledge of which tracts are essential for the recovery of locomotor function in rats after repair is unknown. To assess the mechanism of recovery, we examined the correlation between functional recovery and axonal regeneration. All rats underwent complete cord transection and repair with peripheral nerves, fibroblast growth factor 1, fibrin glue, and spinal fixation. ⋯ To determine which long tracts correlated with recovery, a novel technique of simultaneous bidirectional axonal tracing and immunohistochemical examination of axonal type was used to quantitate the regeneration of corticospinal, rubrospinal, reticulospinal, vestibulospinal, raphespinal, propriospinal, serotonergic, and calcitonin gene-related peptide containing axons. Multiple linear regression analysis revealed recovery of function correlated only with regeneration of corticospinal axons into the gray matter of the lumbar spinal cord (R = 0.977, p < 0.02). For the first time, we show that regeneration of the corticospinal tract into the lumbar gray matter is a mechanism of functional locomotor recovery after complete cord transection and repair.