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
The squamous cell carcinoma (SCC) antigen was determined by radioimmunoassay in the serum of 40 untreated patients with SCC of the oromaxillofacial region. The mean (+/- SEM) serum concentration for these patients (3.8 +/- 0.8 ng/ml) was significantly higher than that of 52 disease-free patients coming to routine postoperative care (1.2 +/- 0.1 ng/ml) and of 74 healthy controls (1.1 +/- 0.07 ng/ml). Using a arbitrary limit of 2.2 ng/ml, pathologic serum levels of SCC were observed in 15 (38%) of 40 untreated patients, whereas only four (7.7%) of 52 tumor-free patients revealed an elevated serum SCC. Serial measurements of SCC were pretherapeutically available in 28 patients as well as during individual therapy and further follow-up. All but one of these patients had a normal serum SCC postoperatively. The authors' results demonstrate that the clinical value of SCC lies mainly in monitoring the course of the disease. Careful follow-up studies should be undertaken to determine whether serial determination of SCC is promising in early prediction of tumor reoccurrence.
Subject(s)
Antigens, Neoplasm/analysis , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/immunology , Facial Neoplasms/immunology , Mouth Neoplasms/immunology , Serpins , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Facial Neoplasms/diagnosis , Facial Neoplasms/therapy , Female , Follow-Up Studies , Humans , Male , Mouth Neoplasms/diagnosis , Mouth Neoplasms/therapy , RadioimmunoassayABSTRACT
In a randomized, double-center, double-blind, parallel group study the analgesic effect of a single dose of paracetamol (1000 mg) and acetyl salicylic acid (1000 mg) was compared with placebo in patients with moderate to severe postoperative pain following the surgical removal of a wisdom tooth. The most important finding was the statistically significantly shorter period until the onset of the action of paracetamol as against acetyl salicylic acid.
