ABSTRACT
BACKGROUND: In the pathology of sporadic inclusion body myositis (sIBM), the relevance of cell stress molecules such as the heat shock protein alphaB-crystallin, particularly in healthy appearing muscle fibres, has remained elusive. METHODS: 10 muscle biopsies from sIBM patients were serially stained for haematoxylin-eosin, trichrome and multi-immunohistochemistry for neural cell adhesion molecule (NCAM), alphaB-crystallin, amyloid precursor protein (APP), desmin, major histocompatibility complex I, beta-amyloid and ubiquitin. Corresponding areas of all biopsies were quantitatively analysed for all markers. Primary myotube cultures were exposed to the proinflammatory cytokines interleukin (IL)-1beta and interferon (IFN)-gamma. RESULTS: In human myotubes exposed to IL-1beta+IFN-gamma, overexpression of APP was accompanied by upregulation of alphaB-crystallin. In sIBM muscle biopsies, over 20% of all fibres displayed accumulation of beta-amyloid or vacuoles/inclusions. A clearly larger fraction of the fibres were positive for alphaB-crystallin or APP. In contrast with the accumulation of beta-amyloid in atrophic fibres, a major part of fibres positive for APP or alphaB-crystallin showed no morphological abnormalities. Expression of APP and alphaB-crystallin significantly correlated with each other and most double positive fibres displayed accumulation of beta-amyloid, vacuoles or an atrophic morphology. In almost all of these fibres, other markers of degeneration/regeneration such as NCAM and desmin were evident as additional indicators of a cell stress response. Some fibres double positive for APP and alphaB-crystallin displayed infiltration by inflammatory cells. CONCLUSION: Our results suggest that alphaB-crystallin is associated with overexpression of APP in sIBM muscle and that upregulation of alphaB-crystallin precedes accumulation of beta-amyloid. The data help to better understand early pathological changes and underscore the fact that a network of cell stress, inflammation and degeneration is relevant to sIBM.
Subject(s)
Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Myositis, Inclusion Body/metabolism , alpha-Crystallin B Chain/biosynthesis , Cells, Cultured , Desmin/metabolism , Humans , Inflammation/metabolism , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/pathology , Myositis, Inclusion Body/pathology , Neural Cell Adhesion Molecules/metabolism , Stress, Physiological , Ubiquitin/metabolismABSTRACT
Spectrophotometric and microspectrophotometric measures of relative spectral transmission were obtained from the cornea, lens, and vitreous body and from the whole eye of young and adult pigeons. Transmission was above 90% throughout the visible spectrum and was maintained at or above 50% into the near-UV at 310 nm. No age-related changes in transmission were found. The results concur with the pigeon's behavioral UV-detection abilities.
