Inclusions Dotaz Zobrazit nápovědu
We describe what we believe to be the fifth case of a degenerative condition of the brain characterized by unusual intracytoplasmic inclusions in neocortical astrocytes, and we review four previous reports of what appears to be the same condition. Whereas these previous cases were characterized by prolonged clinical mental and psychomotor retardation, our case describes a rapid onset in a previously fit and mentally able patient in whom the astrocytic inclusions showed a close association with fibrohyaline vascular degeneration and changes resembling those of Alzheimer's disease. The inclusions, which were most frequent in the second to fourth layers of the frontal, temporal, and occipital cortices but absent from subcortical regions, consisted of large, irregular hyaline bodies surrounding the nucleus and extending into the proximal parts of cell processes. Ultrastructurally they consisted of free ribosomes in a granular and filamentous matrix. They were not bound by a membrane. Lipofuscin granules were associated with them. It is suggested that the inclusions might result from a disturbance of protein metabolism in protoplasmic astrocytes, but their true significance is unknown.
- MeSH
- astrocyty patologie MeSH
- buněčná inkluze patologie MeSH
- demence patologie MeSH
- hyalin MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozek krevní zásobení MeSH
- mozková kůra patologie MeSH
- nemoci mozku patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- MeSH
- buněčná inkluze ultrastruktura MeSH
- dýchání MeSH
- hlodavci anatomie a histologie MeSH
- plíce anatomie a histologie cytologie MeSH
- tělesná hmotnost MeSH
- velikost orgánu MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- buněčná inkluze * MeSH
- epitel ultrastruktura MeSH
- epitelové buňky * MeSH
- krysa rodu Rattus MeSH
- vejcovody cytologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In the present paper we describe needle-shaped and granular cytoplasmic inclusions in the liver cells of mice and rats with experimental porphyria biochemically resembling human porphyria cutanea tarda. The inclusions were inconspicuous in routine histological slides. The ferric ferricyanide reduction reaction, however, enabled us to demonstrate their shape and location within the hepatic lobule. Needle-shaped inclusions are considered to represent a structure specifically seen in experimental porphyrias resembling porphyria cutanea tarda. These structures are similar to the inclusions seen in human porphyria cutanea tarda.
- MeSH
- benzamidy MeSH
- buněčná inkluze ultrastruktura MeSH
- ferrikyanidy chemie MeSH
- herbicidy MeSH
- hexachlorbenzen MeSH
- játra ultrastruktura MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- myši MeSH
- oxidace-redukce MeSH
- polychlorované bifenyly MeSH
- porfyrie chemicky indukované patologie MeSH
- porphyria cutanea tarda patologie MeSH
- potkani Wistar MeSH
- průmyslové fungicidy MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 2,4',5-trichlorobiphenyl MeSH Prohlížeč
- benzamidy MeSH
- ferric ferricyanide MeSH Prohlížeč
- ferrikyanidy MeSH
- fomesafen MeSH Prohlížeč
- herbicidy MeSH
- hexachlorbenzen MeSH
- polychlorované bifenyly MeSH
- průmyslové fungicidy MeSH
Spinocerebellar ataxia type-1 (SCA1) is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are somehow linked to neuronal death. However, owing to lack of a suitable cellular model, the downstream consequences of IIB formation are yet to be resolved. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1 and characterize IIB effects. Using an inducible Sleeping Beauty transposon system, we overexpressed the ATXN1(Q82) gene in human mesenchymal stem cells that are resistant to the early cytotoxic effects caused by the expression of the mutant protein. We characterized the structure and the protein composition of insoluble polyQ IIBs which gradually occupy the nuclei and are responsible for the generation of reactive oxygen species. In response to their formation, our transcriptome analysis reveals a cerebellum-specific perturbed protein interaction network, primarily affecting protein synthesis. We propose that insoluble polyQ IIBs cause oxidative and nucleolar stress and affect the assembly of the ribosome by capturing or down-regulating essential components. The inducible cell system can be utilized to decipher the cellular consequences of polyQ protein aggregation. Our strategy provides a broadly applicable methodology for studying polyQ diseases.
- Klíčová slova
- Ataxin-1, Oxidative stress, Polyglutamine, Protein network, Ribosome, Sleeping beauty transposon,
- MeSH
- ataxin-1 genetika metabolismus MeSH
- intranukleární inkluzní tělíska * metabolismus MeSH
- jaderné proteiny genetika metabolismus MeSH
- lidé MeSH
- oxidační stres MeSH
- proteiny nervové tkáně * genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ataxin-1 MeSH
- jaderné proteiny MeSH
- proteiny nervové tkáně * MeSH
Cell degradation of various origin often starts with an ubiquitinization of damaged proteins and with later production of roughly fibrillar electron-microscopical inclusions. There is a strong immunohistological positivity of ubiquitin in the early intracellular phase. It tends toward an apoptotic lysis either ending with extracellular immunohistologically inert refuse of amyloid type or representing various inter-steps of the degradation process. The ubiquitinization is the most common in neurons and paraneurons. A general importance of ubiquitinization is proved by ubiquitin fibrillar inclusions which were observed in growing old tissue cultures as an expression of programmed cell death. Immunodetection of increased ubiquitin is labour-saving as compared with some classical methods detecting similar lesions particularly in neuropathology.
- MeSH
- buněčná inkluze chemie ultrastruktura MeSH
- buněčné linie MeSH
- fibroblasty chemie ultrastruktura MeSH
- lidé MeSH
- nervová tkáň metabolismus MeSH
- stárnutí buněk MeSH
- ubikvitiny analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ubikvitiny MeSH
Crystalline cytoplasmic needle-shaped inclusions in hepatocytes are considered to represent a specific morphological feature of porphyria cutanea tarda (PCT) and experimental PCT-like porphyrias. The cytoplasmic inclusions, however, are absent in hyperplastic hepatic nodules and hepatocellular carcinomas arising in the course of these conditions. It is assumed that porphyrins and related substances accumulated in hyperplastic and neoplastic hepatic lesions differ from those found in non-neoplastic liver tissue: the highly carboxylated porphyrins are stored in both sites, the crystal-forming substance only in non-proliferating liver tissue.
- MeSH
- benzamidy toxicita MeSH
- buněčná inkluze ultrastruktura MeSH
- experimentální nádory jater chemicky indukované patologie ultrastruktura MeSH
- hepatocelulární karcinom patologie ultrastruktura MeSH
- herbicidy toxicita MeSH
- játra účinky léků patologie ultrastruktura MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- myši inbrední ICR MeSH
- myši MeSH
- nádory jater patologie ultrastruktura MeSH
- porphyria cutanea tarda chemicky indukované patologie MeSH
- zvířata MeSH
- Check Tag
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- benzamidy MeSH
- fomesafen MeSH Prohlížeč
- herbicidy MeSH
Inosine-5'-monophosphate dehydrogenase catalyzes the critical step in the de novo synthesis of guanosine nucleotides: the oxidation of inosine monophosphate to xanthosine monophosphate. This reaction can be inhibited by specific inhibitors, such as ribavirin or mycophenolic acid, which are widely used in clinical treatment when required to inhibit the proliferation of viruses or cells. However, it was recently found that such an inhibition affects the cells, leading to a redistribution of IMPDH2 and the appearance of IMPDH2 inclusions in the cytoplasm. According to their shape, these inclusions have been termed "Rods and Rings" (R&R). In this work, we focused on the subcellular localization of IMPDH2 protein and the ultrastructure of R&R inclusions. Using microscopy and western blot analysis, we show the presence of nuclear IMPDH2 in human cells. We also show that the nuclear pool has an ability to form Rod structures after inhibition by ribavirin. Concerning the ultrastructure, we observed that R&R inclusions in cellulo correspond to the accumulation of fibrous material that is not surrounded by a biological membrane. The individual fibers are composed of regularly repeating subunits with a length of approximately 11 nm. Together, our findings describe the localization of IMPDH2 inside the nucleus of human cells as well as the ultrastructure of R&R inclusions.
- Klíčová slova
- Inosine-5′-monophosphate dehydrogenase, Rods and Rings, correlative light and electron microscopy, electron tomography, inclusions, inhibitors of IMPDH, ultrastructure,
- MeSH
- aktivní transport - buněčné jádro účinky léků MeSH
- buněčné jádro enzymologie metabolismus ultrastruktura MeSH
- cytoplazma enzymologie ultrastruktura MeSH
- HeLa buňky MeSH
- IMP-dehydrogenasa antagonisté a inhibitory chemie metabolismus ultrastruktura MeSH
- inhibitory enzymů farmakologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- IMP-dehydrogenasa MeSH
- IMPDH2 protein, human MeSH Prohlížeč
- inhibitory enzymů MeSH
Cell suspensions of the haloarchaea Halorubrum sodomense and Halobacterium salinarum and the extremely halophilic bacterium Salinibacter ruber (Bacteroidetes) in saturated solutions of chlorides and sulfates (NaCl, KCl, MgSO4·7H2O, K2SO4, and (NH4)Al(SO4)2·12H2O) were left to evaporate to produce micrometric inclusions in laboratory-grown crystals. Raman spectra of these pinkish inclusions were obtained using a handheld Raman spectrometer with green excitation (532 nm). This portable instrument does not include any microscopic tool. Acceptable Raman spectra of carotenoids were obtained in the range of 200-4000 cm-1. This detection achievement was related to the mode of illumination and collection of scattered light as well as due to resonance Raman enhancement of carotenoid signals under green excitation. The position of diagnostic Raman carotenoid bands corresponds well to those specific carotenoids produced by a given halophile. To our best knowledge, this is the first study of carotenoids included in the laboratory in crystalline chlorides and sulfates, using a miniature portable Raman spectrometer. Graphical abstract ᅟ.
- Klíčová slova
- Carotenoids, Halophilic prokaryotes, Inclusions, Miniature Raman spectrometer, Salts,
- MeSH
- Bacteroidetes chemie MeSH
- chlorid draselný chemie MeSH
- chlorid sodný chemie MeSH
- Halobacterium salinarum chemie MeSH
- Halorubrum chemie MeSH
- karotenoidy analýza MeSH
- limita detekce MeSH
- Ramanova spektroskopie přístrojové vybavení MeSH
- sírany chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chlorid draselný MeSH
- chlorid sodný MeSH
- karotenoidy MeSH
- sírany MeSH