Desmin Dotaz Zobrazit nápovědu
Prípady náhlych a neočakávaných úmrtí z kardiálnych príčin sú častým predmetom vyšetrovania post mortem v súdnolekárskej praxi. Detekcia čerstvých ischemických zmien alebo čerstvého infarktu myokardu je, makroskopicky a mikroskopicky pri konvenčnom farbení tkanivových rezov, niekedy nemožná. Cieľom predkladanej práce je priblížiť možnosti využitia detekcie dezmínu v myokarde pomocou imunohistochemického vyšetrenia a moderných metód hodnotenia jeho výsledkov v diagnostike náhlej a neočakávanej srdcovej smrti.
Cases of sudden and unexpected deaths from cardiac causes are a frequent subject of post mortem investigation in everyday forensic practice. They occur in all age categories. Morphological findings at autopsy may reveal pathological changes in the myocardium, e.g. acute infarction, all forms of myocarditis, cardiomyopathy of various aetiologies, congenital coronary artery anomalies, lesions of the cardiac conduction system and primary heart tumours, especially in the elderly. At a younger age, the autopsy findings are mostly poor in morphological changes and the cause of death is often determined per exclusionem as a functional diagnosis of cardiac failure. Early ischemic changes or early myocardial infarction is sometimes impossible to detect macroscopically and also microscopically in tissue sections with conventional staining. Desmin is cytoplasmic structural protein found in striated muscle, associated with Z-lines in muscle cell and is sensitive to oxygen deficiency. In myocardial samples taken at autopsy, desmin can be visualized by immunohistochemistry with specific antibody-antigen reaction. The aim of the presented work is to approach the possibilities of using desmin detection in the myocardium using immunohistochemical examination and modern methods of evaluating its results using image analysis in the diagnostics of sudden and unexpected cardiac death.
Desmin mutations cause familial and sporadic cardiomyopathies. In addition to perturbing the contractile apparatus, both desmin deficiency and mutated desmin negatively impact mitochondria. Impaired myocardial metabolism secondary to mitochondrial defects could conceivably exacerbate cardiac contractile dysfunction. We performed metabolic myocardial phenotyping in left ventricular cardiac muscle tissue in desmin knock-out mice. Our analyses revealed decreased mitochondrial number, ultrastructural mitochondrial defects, and impaired mitochondria-related metabolic pathways including fatty acid transport, activation, and catabolism. Glucose transporter 1 and hexokinase-1 expression and hexokinase activity were increased. While mitochondrial creatine kinase expression was reduced, fetal creatine kinase expression was increased. Proteomic analysis revealed reduced expression of proteins involved in electron transport mainly of complexes I and II, oxidative phosphorylation, citrate cycle, beta-oxidation including auxiliary pathways, amino acid catabolism, and redox reactions and oxidative stress. Thus, desmin deficiency elicits a secondary cardiac mitochondriopathy with severely impaired oxidative phosphorylation and fatty and amino acid metabolism. Increased glucose utilization and fetal creatine kinase upregulation likely portray attempts to maintain myocardial energy supply. It may be prudent to avoid medications worsening mitochondrial function and other metabolic stressors. Therapeutic interventions for mitochondriopathies might also improve the metabolic condition in desmin deficient hearts.
- MeSH
- aminokyseliny metabolismus MeSH
- citráty metabolismus MeSH
- desmin * genetika metabolismus MeSH
- glukosa metabolismus MeSH
- hexokinasa * genetika metabolismus MeSH
- kardiomyopatie * genetika metabolismus MeSH
- kreatinkinasa, mitochondriální forma metabolismus MeSH
- mastné kyseliny metabolismus MeSH
- myokard metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- oxidativní fosforylace MeSH
- přenašeč glukosy typ 1 metabolismus MeSH
- proteomika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Autoři studovali expresi S-100 proteinu, aktinu hladké svaloviny, svalového aktinu a dezminu v kloubních chrupavkách odebraných při artroskopickém vyšetření u 8 pacientů s různým stup- něm osteoartritidy kolenního kloubu. Ve všech případech byly buňky chrupavčité tkáně zřetelně pozitivní v reakci k průkazu S-100 proteinu. Aktin pozitivní chondrocyty byly zaznamenány ve 4 vzorcích s reparativními změnami při osteoartritidě provázenými tvorbou fibrózní chrupavčité tkáně. Navíc u jednoho z těchto vzorků byly současně pozorovány dezmin pozitivní chondrocyty ve vrstvě chrupavčité tkáně vyplňující povrchový defekt v kloubní chrupavce. Expresi dezminu je možno chápat jako důsledek reakce na trauma nebo výraz vrozené abnormality. Chondrocyty prav- děpodobně získaly během hojivého procesu některé rysy buněk hladké svaloviny, neboť dezmin je do značné míry marker svalových buněk. Tento fakt by mohl podporovat původní předpoklad au- torů, že chondrocyty exprimující svalové markery by mohly být označovány v analogii s myofib- roblasty jako myochondrocyty a myochondroblasty. Je pravděpodobné, že takováto transformace imunofenotypu chondrocytů je v průběhu hojení defektů chrupavky dosti častá, i když možná pou- ze přechodného charakteru.
We studied the results of immunostaining for S-100 protein, alpha-smooth muscle actin, muscle specific actin and desmin in articular cartilage specimens obtained during an arthroscopy from eight patients with different degrees of osteoarthritis of the knee joint. In all cases, most of the cartilage cells were strongly positive for S-100 protein. Actin positive chondrocytes were present in four samples showing repair cartilage changes with occurrence of fibrocartilage tissue. Moreover, in one case, we observed typical desmin-positive chondrocytes in the layer of cartilage filling the defect of the articular cartilage surface. The expression of desmin can be regarded as a reaction to trauma or the indication of an inherent abnormality. The chondrocytes probably switched on smooth muscle features during the healing process, because desmin is to a great extent a typical muscle cell marker. This fact could probably support our previous supposition that cartilage cells expressing muscle markers could be designated as myochondroblasts and myochondrocytes analogously to the terminology of myofibroblasts. It is possible that during the healing of the cartilage defects, such a transformation of the immunophenotype of the cartilage cells is quite frequent, but it could also be only transient nature only
We describe the expression and distribution patterns of nestin, desmin and vimentin in intact and regenerating muscle spindles of the rat hind limb skeletal muscles. Regeneration was induced by intramuscular isotransplantation of extensor digitorum longus (EDL) or soleus muscles from 15-day-old rats into the EDL muscle of adult female inbred Lewis rats. The host muscles with grafts were excised after 7-, 16-, 21- and 29-day survival and immunohistochemically stained. Nestin expression in intact spindles in host muscles was restricted to Schwann cells of sensory and motor nerves. In transplanted muscles, however, nestin expression was also found in regenerating "spindle fibers", 7 and 16 days after grafting. From the 21st day onwards, the regenerated spindle fibers were devoid of nestin immunoreactivity. Desmin was detected in spindle fibers at all developmental stages in regenerating as well as in intact spindles. Vimentin was expressed in cells of the outer and inner capsules of all muscle spindles and in newly formed myoblasts and myotubes of regenerating spindles 7 days after grafting. Our results show that the expression pattern of these intermediate filaments in regenerating spindle fibers corresponds to that found in regenerating extrafusal fibers, which supports our earlier suggestion that they resemble small-diameter extrafusal fibers.
- MeSH
- desmin analýza MeSH
- financování organizované MeSH
- kosterní svalová vlákna chemie MeSH
- kosterní svaly chemie transplantace ultrastruktura MeSH
- krysa rodu rattus MeSH
- myoblasty chemie MeSH
- nervosvalová vřeténka chemie MeSH
- potkani inbrední LEW MeSH
- proteiny intermediálních filament analýza MeSH
- proteiny nervové tkáně analýza MeSH
- regenerace MeSH
- Schwannovy buňky chemie MeSH
- vimentin analýza MeSH
- zadní končetina MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- abstrakt z konference MeSH
Background: The pleomorphic clinical presentation makes the diagnosis of desminopathy difficult. We aimed to describe the prevalence, phenotypic expression, and mitochondrial function of individuals with putative disease-causing desmin (DES) variants identified in patients with an unexplained etiology of cardiomyopathy. Methods: A total of 327 Czech patients underwent whole exome sequencing and detailed phenotyping in probands harboring DES variants. Results: Rare, conserved, and possibly pathogenic DES variants were identified in six (1.8%) probands. Two DES variants previously classified as variants of uncertain significance (p.(K43E), p.(S57L)), one novel DES variant (p.(A210D)), and two known pathogenic DES variants (p.(R406W), p.(R454W)) were associated with characteristic desmin-immunoreactive aggregates in myocardial and/or skeletal biopsy samples. The individual with the novel DES variant p.(Q364H) had a decreased myocardial expression of desmin with absent desmin aggregates in myocardial/skeletal muscle biopsy and presented with familial left ventricular non-compaction cardiomyopathy (LVNC), a relatively novel phenotype associated with desminopathy. An assessment of the mitochondrial function in four probands heterozygous for a disease-causing DES variant confirmed a decreased metabolic capacity of mitochondrial respiratory chain complexes in myocardial/skeletal muscle specimens, which was in case of myocardial succinate respiration more profound than in other cardiomyopathies. Conclusions: The presence of desminopathy should also be considered in individuals with LVNC, and in the differential diagnosis of mitochondrial diseases.
- Publikační typ
- časopisecké články MeSH
Gliosarkóm (GS) je relatívne vzácny variant glioblastómu, charakterizovaný bifázickou gliálnou a mezenchymálnou diferenciáciou. Sarkomatózna časť najčastejšie pripomína fibrosarkóm alebo tzv. malígny fibrózny histiocytóm. Vzácne je v GS prítomná heterológna diferenciácia vo forme osteosarkómu, chondrosarkómu, liposarkómu, leiomyosarkómu, skvamóznej alebo žľazovej malígnej epiteliálnej diferenciácie, alebo diferenciácie pripomínajúcej primitívny neuroektodermálny tumor (PNET). Keď je v GS prítomná rabdomyosarkómová diferenciácia, je vo forme malígnych vretenovitých buniek s priečne pruhovanými bunkami alebo okrúhlymi rabdomyoblastami, pripomínajúca embryonálny rabdomyosarkóm. V kazuistike popisujeme GS s komponentou pripomínajúcou alveolárny rabdomyosarkóm. Nádor rástol v solídnych a alveolárnych formáciách a bol zložený z nediferencovaných primitívnych malých okrúhlych buniek s minimálnou cytoplazmou, nápadne zvýšenou mitotickou aktivitou a početnými apoptózami. Rabdomyosarkomatózna diferenciácia bola potvrdená pozitívnou imunohistochemickou reakciou na dezmín a myogenín. Podľa naších vedomostí, takýto histologický vzor nebol v GS doposiaľ popísaný. V krátkosti je prebraná diferenciálna diagnóza prípadu.
Gliosarcoma (GS) is a relatively rare glioblastoma variant characterized by biphasic glial and mesenchymal differentiation patterns. The sarcomatous part most commonly resembles fibrosarcoma or so-called malignant fibrous histiocytoma. Rarely, GS shows heterologous lines of differentiation in the form of osteosarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, squamous or glandular malignant epithelial differentiation, or primitive neuroectodermal tumor (PNET)-like foci. When rhabdomyoblastic differentiation occurs, it is in the form of malignant spindle cells, with cross-striated strap cells or rounded rhabdomyoblasts reminiscent of the embryonal type of rhabdomyosarcoma. We are reporting a case of GS with an alveolar rhabdomyosarcoma-like component. The tumor consisted of poorly differentiated primitive small round cells growing in a solid and alveolar pattern, with minimal cytoplasm, markedly elevated mitotic activity and numerous apoptotic nuclei. Rhabdomyosarcomatous differentiation was confirmed by desmin and myogenin immunopositivity. To the best of our knowledge, this histologic pattern has not been previously reported in GS. Differential diagnostic considerations are discussed.
- Klíčová slova
- alveolárny rabomyosarkóm,
- MeSH
- alveolární rhabdomyosarkom * imunologie patologie MeSH
- desmin diagnostické užití MeSH
- gliosarkom * imunologie patologie terapie MeSH
- imunohistochemie metody využití MeSH
- lidé MeSH
- myogenin diagnostické užití MeSH
- nádorová transformace buněk * imunologie klasifikace patologie MeSH
- radioterapie metody MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
