0000000000075020
AUTHOR
Dominique S. Tews
Morphology of experimentally denervated and reinnervated rat facial muscle I. Histochemical and histological findings
The morphological changes in rat facial muscles were evaluated after permanent denervation and were compared with findings after immediate reinnervation. Thirty rats underwent transection of the left and right facial nerves immediately followed by hypoglossal-facial nerve anastomosis on the right side (muscular reinnervation) and removal of 8-10 mm of the facial plexus on the left side (permanent muscular denervation). Levator labii muscle samples of both sides were collected sequentially at 2, 6, 7, 10, 20, and 24 weeks after surgery and submitted to routine histological and enzyme histochemical staining procedures. In normal levator labii muscles a typical "chessboard" pattern was found, …
DNA-fragmentation and expression of apoptosis-related proteins in experimentally denervated and reinnervated rat facial muscle
Muscle fibres may undergo apoptotic cell death in several neuromuscular disorders such as denervated muscle fibres in spinal muscular atrophies. We investigated DNA-fragmentation (in situ by the TUNEL-method) and expression of apoptosis-associated proteins in experimentally denervated and reinnervated rat facial muscle up to 24 weeks after surgery to evaluate the rate and time lapse of apoptotic muscle fibre loss. While denervated muscle displayed constantly high rates of DNA-fragmentation, denervated and immediately reinnervated muscle showed a distinct decrease of primarily elevated DNA-cleavage, finally resembling rates of normal controls. Denervated muscle fibres revealed strong immunor…
Expression of apoptosis-related proteins, p53, and DNA fragmentation in sarcomas of the pulmonary artery
Department of Molecular Cell Biology, Max-Planck Institute for Physiology and Clinical Re-search, Bad Nauheim, Germany.The results of this article were presented at theannual Meeting of the German Society of Pathol-ogy, May 26–29, 1999, Jena, Germany.The authors acknowledge the excellent technicalsupport of Sandra Gerecht and Antonietta Ras-tiello, the photographic support of Peter Pulkowskiand Thomas Bo¨hm, and the helpful comments andcritical reading of the manuscript by Dr. NorbertSpeich (Imogen, Bonn, Germany) and Dr. Ron Un-ger.Address for correspondence: Andreas Gaumann,M.D., Department of Molecular Cell Biology, Max-Planck Institute for Physiology and Clincial Re-search, W. G. Kerckh…
Expression of cell adhesion molecules in inflammatory myopathies.
We examined the expression of cell adhesion molecules in 25 cases of inflammatory myopathies. Inflammatory myopathies showed upregulation of adhesion molecules. ICAM-1 was strongly expressed on endothelial cells as well as on fibroblasts and infiltrating leukocytes while the expression of VCAM-1, similar in its distribution, was much weaker. A few muscle fibers in polymyositis revealed sarcolemmal labeling for ICAM-1. ELAM-1 showed only weak expression on vessels. The inflammatory cellular infiltrates contained varying amounts of cells bearing the VCAM-1 ligand VLA-4 and the ELAM-1 ligand SLeX as well as large amounts of cells expressing LFA-1 alpha and beta, ligands of ICAM-1.
Role of nitric oxide and nitric oxide synthases in experimental models of denervation and reinnervation.
Nitric oxide (NO) is a short-living free molecule synthesized by three different isoforms of nitric oxide synthases (NOS)—neuronal NOS, endothelial NOS, and inducible NOS—associated with neuromuscular transmission, muscle contractility, mitochondrial respiration, and carbohydrate metabolism in skeletal muscle. Neuronal NOS is constitutively expressed at the muscle fiber sarcolemma linked to the dystrophin-glycoprotein complex and concentrated at the neuromuscular endplate. There is increasing evidence that altered expression of neuronal NOS plays a role in muscle fiber damage in neuromuscular diseases such as dystrophinopathies and denervating disorders. Although there have been some previo…
Cell Death and Oxidative Damage in Inflammatory Myopathies
There is evidence that muscle fibers in denervating disorders and muscular dystrophies undergo apoptosis. In 21 patients with autoimmune inflammatory myopathies, we found no features of muscle fiber apoptosis such as DNA fragmentation or expression of apoptosis-related proteins. However, muscle fibers in myositis displayed distinct up-regulation of inducible and neuronal nitric oxide synthase (NOS). While inducible NOS was distinctly up-regulated on the sarcolemma of all kinds of muscle fibers neuronal NOS displayed increased expression in the sarcoplasm of damaged as well as atrophic muscle fibers. There were no disease-specific patterns in the different myositis subtypes. Enhanced express…
Intrinsic Expression of Drug Resistance-Associated Factors in Meningiomas
Meningiomas, commonly benign tumors, rarely display aggressive behavior by recurrences and invasion. In addition to surgery, irradiation is beneficial for recurrent, atypical, and malignant meningiomas. The role of chemotherapy, however, remains controversial, although there is evidence that meningiomas respond well to adjuvant chemotherapy. A major obstacle in chemotherapy remains drug resistance with reduced cellular drug accumulation through membrane efflux pumps, drug detoxification, and alterations in drug target specificity. In 84 classic, atypical, and malignant meningiomas, the immunohistochemical expression profile of P-glycoprotein (P-gp), multidrug resistance-associated protein (…
Hamartoma of the triceps surae muscle.
A 9-year-old, otherwise healthy girl presented with a 5-year history of pain in her right calf with retarded growth and development of an equinus contracture of her right leg. Magnetic resonance imaging showed an irregular mass with heterogeneous enhancement after contrast in her right triceps surae muscles, especially the soleus. Histological studies of this triceps surae muscle tissue revealed a haphazard distribution of adipose and connective tissue, striated and smooth muscle cells, vessels and lymphoid follicles, as well as nerve bundles which, together, were considered components of a hamartoma.
Cell death and oxidative stress in gliomas.
In gliomas, apoptosis and necrosis are determined by a number of promoting and inhibiting factors including oxidative cell stress mediated by nitric oxide synthases (NOS) and reduced by superoxide dismutases. Therefore, in 46 gliomas (including astrocytomas, oligodendrogliomas, oligo-astrocytomas, and glioblastomas), the relationship of apoptosis and necrosis and the expression of apoptosis-promoting (p53, bax, Fas, Fas-L) and inhibiting (bcl-2) factors as well as of different isoforms of NOS (NOSb, NOSe, NOSi) and manganese superoxide dismutase (MnSOD) were studied. Apoptosis was measured in situ by the TUNEL method while expression profiles of apoptosis-related and oxidative stress-associ…
Cytokine expression profile in idiopathic inflammatory myopathies.
Cytokines have been shown to be potent inducers of major histocompatibility complexes (MHC) class I and II as well as of cell adhesion molecules in muscle tissue cultures, indicating that cytokines may play a role in mediating muscle fiber damage in inflammatory myopathies. We found in 21 cases of autoimmune myositis various amounts of inflammatory cells expressing interleukin (IL)-1 alpha and -beta, IL-2, IL-4, tumor necrosis factor (TNF) -alpha and -beta, and interferon (IFN)-gamma and its receptor. Muscle fibers displayed enhanced expression of IL-1 alpha and -beta, IL-2, and TNF-alpha. Upregulation of cytokines was strongest at sites of cellular infiltration typical for the respective m…
DNA-fragmentation and expression of apoptosis-related proteins in muscular dystrophies
Although numerous sarcolemmal protein defects in muscular dystrophies have been identified, the mechanisms linking these defects and muscle fibre degeneration are not fully characterized. As there is evidence that apoptosis is part of muscle fibre loss in dystrophin-deficient mdx-mice, apoptotic muscle fibre death may also play a role in humans with muscular dystrophies. We investigated in-situ DNA-fragmentation by the TUNEL-method and expression of apoptosis-related proteins immunohistochemically in 14 children suffering from deficiencies of dystrophin, adhalin, and merosin, and found TUNEL-positive chromatin-cleavage of muscle fibre nuclei in about 10% of non-necrotic muscle fibres. DNA-f…
Apoptosis-related Proteins in Skeletal Muscle Fibers of Spinal Muscular Atrophy
There is evidence that apoptosis in spinal muscular atrophies (SMA) is not restricted to motor neurons but also affects muscle fibers. Studying the expression of several apoptosis-associated proteins we found constant expression of bax in muscle fibers, which promoted cell death. The expression of bax correlated with defective innervation of muscle fibers was also indicated by upregulation of N-CAM. While in early-onset SMA atrophic as well as normo- and hypertrophic muscle fibers displayed expression of bax, muscle fibers in late-onset SMA and peripheral neuropathies showed bax-expression only in atrophic fibers. Other investigated apoptosis-associated factors comprised interleukin-1 beta …
Expression of adhesion factors and degrading proteins in primary and secondary glioblastomas and their precursor tumors.
In tumor tissue specimens of 27 primary and 17 secondary glioblastomas and the precursor lesions, the immunohistochemical expression patterns of the membrane protein CD44s, the basal lamina proteins laminin, collagen IV, and fibronectin, the lectin galectin-3 recognizing tenascin and N-CAM as well as of the matrix-degrading enzymes matrix metalloproteinase MMP-2 and MMP-9, and cathepsin D were studied. Besides expression of basal lamina proteins in vessels, all glioblastomas and the precursor lesions showed strong immunoreactivity of CD44s, tenascin, galectin-3, and N-CAM which were restricted to solid tumor masses. Present in solid tumor areas, MMP-2, MMP-9 and cathepsin D were also strong…
Expression Profile of Stress Proteins, Intermediate Filaments, and Adhesion Molecules in Experimentally Denervated and Reinnervated Rat Facial Muscle
The immunohistochemical profiles of ubiquitin, heat shock protein 70, alpha-B-crystallin, desmin, vimentin, neural cell adhesion molecule (N-CAM), and tenascin in rat facial muscle were studied after permanent denervation by transection of the facial plexus on one side and compared with findings after immediate reinnervation by hypoglossal-facial nerve anastomosis subsequent to transection on the contralateral side. Levator labii muscle samples were collected sequentially at 2, 6, 7, 10, 20, and 24 weeks after surgery. Normal levator labii muscle fibers showed physiological expression of desmin and alpha-B-crystallin. Denervated rat facial muscle displayed distinct up-regulation of ubiquiti…
Expression of different isoforms of nitric oxide synthase in experimentally denervated and reinnervated skeletal muscle.
Denervated muscle fibers express enhanced levels of stress and apoptosis-associated proteins and undergo apoptosis. In experimentally denervated and reinnervated rat facial muscle, we now evaluate changes in the expression patterns of different isoforms of nitric oxide synthase (NOS)-generating nitric oxide (NO), which mediates oxidative stress and apoptosis. Physiological expression of NOS corresponds to a constant sarcolemmal staining pattern for neuronal NOS (nNOS) and a patchy sarcolemmal and weak sarcoplasmic labeling for the endothelial NOS-isoform, with no expression for inducible NOS (iNOS). Denervated muscle displayed distinct downregulation of nNOS with preserved expression of dys…
Adhesive and invasive features in gliomas
Summary This study aims at the in situ identification of factors mediating glioma cell invasion requiring adhesion, extracellular matrix degradation, and migration. Fortyfive gliomas (astrocytomas, glioblastomas, oligodendrogliomas, and mixed gliomas) were investigated for the immunohistochemical expression of the membrane protein CD44s, the basal lamina proteins laminin, collagen IV, and fibronectin, the lectin galectin-3 recognizing tenascin and N-CAM, as well as for the matrix-degrading enzymes metalloproteinases MMP-2, MMP-9, and cathepsin D. Besides vessels expressing basal lamina proteins, tenascin, MMP-2, MMP-9, and galectin-3, tumor cells revealed strong immunoreactivity for CD44s, …