SEARCH · Search PubMed

Results for “Inclusion”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources

PubMed1984

Intranuclear inclusions in muscle, nervous tissue, and adrenal gland.

A 30-year-old man had had chronic progressive wasting and weakness of muscles for 17 years. A muscle biopsy 5 years prior to death revealed myopathic changes were rimmed vacuoles and intranuclear inclusions which corresponded to "inclusion body myositis". At autopsy, intranuclear inclusions were observed in neurons, oligodendroglia, and in parenchymal cells of the adrenal medulla. Ultrastructurally, the inclusions in muscles, nervous tissue, and adrenal medulla were identical and consisted of abnormal tubulolinear structures measuring 10-20 nm in diameter. Similar inclusions have been reported in muscles with "inclusion body myositis" and in the nervous system with "neuronal intranuclear hyaline inclusion disease", respectively. Absence of clinical symptoms related to the CNS and adrenal gland, and well-preserved parenchymal cells in these organs of our patient suggest a benign nature of the disease except in the muscular system. Attempts to isolate a virus from the brain were fruitless . This patient may serve to connect both diseases in muscles and the nervous system, and to disclose the etiology of these inclusions.

Adrenal Glands↗

PubMed1996

An appraisal of the banded and paracrystalline cytoplasmic inclusions induced in cymbidium mosaic potexvirus- and odontoglossum ringspot tobamovirus infected orchid cells using confocal laser scanning microscropy.

The cymbidium mosaic potexvirus (CyMV) banded inclusions and the odontoglossum ringspot tobamovirus (ORSV) paracrystalline inclusions were studied in flowers and leaves of nine orchid cultivars using the confocal laser scanning microscope. The inclusions varied in length and width and were mostly located adjacent to the cell walls. Some ORSV inclusions fully extended across entire infected cells. We propose that the CyMV banded inclusion was formed from virus aggregates which aligned as periodical stacked layers, appearing as cross bands. The virus aggregates were folded into flexible inclusions, giving rise to various shapes and forms. The ORSV paracrystalline inclusions were observed as needle-like crystals. The confocal laser scanning microscope is an effective tool for the study of the three-dimensional structures of plant virus induced inclusions.

Enzyme-Linked Immunosorbent Assay↗

PubMed2004

alpha-Internexin aggregates are abundant in neuronal intermediate filament inclusion disease (NIFID) but rare in other neurodegenerative diseases.

Abnormal neuronal aggregates of alpha-internexin and the three neurofilament (NF) subunits, NF-L, NF-M, and NF-H have recently been identified as the pathological hallmarks of neuronal intermediate filament (IF) inclusion disease (NIFID), a novel neurological disease of early onset with a variable clinical phenotype including frontotemporal dementia, pyramidal and extrapyramidal signs. alpha-Internexin, a class IV IF protein, a major component of inclusions in NIFID, has not previously been identified as a component of the pathological protein aggregates of any other neurodegenerative disease. Therefore, to determine the specificity of this protein, alpha-internexin immunohistochemistry was undertaken on cases of NIFID, non-tau frontotemporal dementias, motor neuron disease, alpha-synucleinopathies, tauopathies, and normal aged control brains. Our results indicate that class IV IF proteins are present within the pleomorphic inclusions of all cases of NIFID. Small subsets of abnormal neuronal inclusions in Alzheimer's disease, Lewy body diseases, and motor neuron disease also contain epitopes of alpha-internexin. Thus, alpha-internexin is a major component of the neuronal inclusions in NIFID and a relatively minor component of inclusions in other neurodegenerative diseases. The discovery of alpha-internexin in neuronal cytoplasmic inclusions implicates novel mechanisms of pathogenesis in NIFID and other neurological diseases with pathological filamentous neuronal inclusions.

Adult↗

PubMed2000

Advanced glycation endproduct-modified superoxide dismutase-1 (SOD1)-positive inclusions are common to familial amyotrophic lateral sclerosis patients with SOD1 gene mutations and transgenic mice expressing human SOD1 with a G85R mutation.

To clarify the biological significance of the neuronal Lewy body-like hyaline inclusions and astrocytic hyaline inclusions characteristically found in patients with familial amyotrophic lateral sclerosis with superoxide dismutase-1 (SOD1) gene mutations and in transgenic mice expressing human SOD1 with G85R mutation, the detailed protein composition in both types of inclusions was immunohistochemically analyzed using 45 different antibodies. Both types of inclusions had very strong immunoreactivity for SOD1. The SOD1-positive inclusions in both cell types were also immunoreactive for the insoluble advanced glycation endproducts (AGEs) such as Nepsilon-(carboxymethyl)lysine (CML), pyrraline and pentosidine: both inclusions in both conditions were ultrastructurally composed of the granule-coated fibrils that had immunoreactivities to CML and pyrraline. Both types of inclusions were negative for stress-response proteins (SRPs), 4-hydroxy-2-nonenal (HNE), acrolein, nitric oxide synthases (NOSs) and nitrotyrosine as representative markers of oxidative stress. The neurons and astrocytes of the normal individuals and non-transgenic mice showed no significant immunoreactivity for SOD1, AGEs, SRPs, HNE, acrolein, NOSs or nitrotyrosine. Our results suggest that a portion of the SOD1 composing both type of inclusions, probably toxic mutant SOD1, is modified by the AGEs, and that the formation of the AGE-modified SOD1 is one of the mechanisms responsible for the aggregation involving no significant oxidative mechanisms.

Adult↗

PubMed1987

Lead-induced inclusion bodies in rat kidney after perinatal treatment with lead and disulfiram.

The presence of inclusion bodies in renal proximal tubules was studied in rats exposed to lead and/or disulfiram (tetraethylthiuram disulfide). Pregnant rats were treated with only lead acetate (0.25% Pb in the drinking water), only disulfiram (0.1 mmol/kg p.o. twice a week) or with both lead acetate and disulfiram from day 1 of pregnancy and until the offspring were 4 weeks of age. After parturition the disulfiram was given s.c. directly to the offspring instead of to the dams. Treatment was discontinued at weaning and tissue samples from renal cortex were studied by electron microscopy. In lead-treated dams inclusions were present in nuclei of renal proximal tubule cells in the 3 segments with the highest incidence in the middle segment. Inclusions were also present in the cytoplasm. In the offspring, indirectly exposed to lead via the dams, inclusions were present in all 3 segments. No inclusions were present in control rats or in disulfiram-treated rats. Combined treatment with lead and disulfiram resulted in a marked decrease in the incidence of inclusion bodies both in the dams and in the offspring compared to in rats treated with only lead. Diethyldithiocarbamate, a major metabolite of disulfiram, forms a lipophilic complex with lead, and is known to cause pronounced effects on the tissue distribution of lead. The present investigation shows that lead inclusion bodies are formed in the offspring indirectly exposed to lead via the dams during gestation and lactation. Concurrent exposure to disulfiram reduces the incidence of inclusion bodies in renal proximal tubules, probably due to formation of a lead-dithiocarbamate complex.

Animals↗

PubMed1975

Pancreatic inclusions and its relation to boric acid poisoning: review of the literature and report of a case.

It is known among forensic and pediatric pathologists that the demonstration of pancreatic inclusions is considered to have diagnostic significance in cases of boric acid poisoning. Fisher was the first to suggest a causal relationship between the inclusions and boric acid toxicity. Valdes-Dapena and Arey paid particular attention to the pancreatic inclusions in reviewing the literature of cases of boric acid poisoning. They found the inclusions in 6 of the 55 autopsies. This paper describes the finding of pancreatic inclusions in a fatal case of gastro-enteritis not associated with boric acid intoxication. The nature of the inclusion bodies was studied by light and electron microscopy. Ultrastructurally, the cytoplasmic inclusions represent a non-specific autophagic cell degenerative process. Toxicological examination of postmortem blood and viscera showed no evidence of boric acid toxicity. The desirability of toxicological analysis in cases of boric acid poisoning and the restricted value of pancreatic inclusions as a diagnostic tool are emphasised.

Boric Acids↗

PubMed2005

Neuronal inclusions in degenerative disorders Do they represent static features or a key to understand the dynamics of the disease?

This brief paper analyzes a few degenerative diseases expressing as movement disorders and featuring at sub-cellular level the presence of neuronal inclusions in selective brain regions. We will first draw a short draft of representative neurological diseases featuring inclusion bodies by describing the type of inclusions occurring in various disorders and analyzing both common features and distinctive aspects. As a further step, we move from the bed to the bench side discussing recent developments obtained from experimental models of these disorders which shed new light into the cause and progression of neuronal inclusions, thus helping to understand the pathophysiology of neuronal degeneration underlying movement disorders. In line with this, we will focus on recent studies which led to reproduce neuronal inclusions in vivo and in vitro by manipulating selective cellular structures/enzymatic pathways. In this way, we will try to encompass the dynamics of inclusion formation based on their fine ultrastructure and the analysis of the molecular components as well as their subcellular compartmentalization trying to relate the dynamics of inclusion formation and the pathophysiology of the disease process. An emphasis will be made on the ubiquitin proteasome system and Parkinson's disease where the analysis of neuronal inclusions enlightened potential therapeutic strategies to occlude the progression of this neuronal degeneration featured by movement disorders.

Animals↗

PubMed2005

Effects of non-contractile inclusions on mechanical performance of skeletal muscle.

Glycogen storage disease II is an inherited progressive muscular disease in which the lack of functional acid 1-4 alpha-glucosidase results in the accumulation of lysosomal glycogen. In the present study, we examine the effect of these non-contractile inclusions on the mechanical performance of skeletal muscle. To this end, force developed in an isometrically contracting slice of a muscle was calculated with a finite element model. Force was calculated at several inclusion densities and distributions and compared to muscle lacking inclusions. Furthermore, ankle dorsal flexor torque was measured in situ of alpha-glucosidase null mice of 6 months of age and unaffected litter mates as was inclusion density in the dorsal flexor muscles. The calculated force loss was shown to be almost exclusively dependent on the inclusion density and less on the type of inclusion distribution. The force loss predicted by the model (6%) on the basis of measured inclusion density (3.3%) corresponded to the loss in mass-normalized strength in these mice measured in situ (7%). Therefore, we conclude that the mechanical interaction between the non-contractile inclusions and the nearby myofibrils is a key factor in the loss of force per unit muscle mass during early stages of GSD II in mice. As glycogen accumulation reaches higher levels in humans, it is highly probable that the impact of this mechanical interaction is even more severe in human skeletal muscle.

Animals↗

PubMed2006

Ultrastructural analysis of chlamydial antigen-containing vesicles everting from the Chlamydia trachomatis inclusion.

Several chlamydial antigens have been detected in the infected epithelial cell cytosol and on the host cell surface prior to their presumed natural release at the end of the 72-96 h developmental cycle. These extra-inclusion antigens are proposed to influence vital host cell functions, antigen trafficking and presentation and, ultimately, contribute to a prolonged inflammatory response. To begin to dissect the mechanisms for escape of these antigens from the chlamydial inclusion, which are enhanced on exposure to antibiotics, polarized endometrial epithelial cells (HEC-1B) were infected with Chlamydia trachomatis serovar E for 36 h or 48 h. Infected cells were then exposed to chemotactic human polymorphonuclear neutrophils not loaded or pre-loaded in vitro with the antibiotic azithromycin. Viewed by electron microscopy, the azithromycin-mediated killing of chlamydiae involved an increase in chlamydial outer membrane blebbing followed by the appearance of the blebs in larger vesicles (i) everting from but still associated with the inclusion as well as (ii) external to the inclusion. Evidence that the vesicles originated from the chlamydial inclusion membrane was shown by immuno-localization of inclusion membrane proteins A, F, and G on the vesicular membranes. Chlamydial heat shock protein 60 (chsp60) copies 2 and 3, but not copy 1, were released from RB and incorporated into the everted inclusion membrane vesicles and delivered to the infected cell surface. These data represent direct evidence for one mechanism of early antigen delivery, albeit membrane-bound, beyond the confines of the chlamydial inclusion.

Amino Acid Sequence↗

PubMed2006

Neuronal inclusions in sporadic motor neuron disease are negative for alpha-synuclein.

Alpha-synuclein has been implicated in neurodegenerative diseases characterized by Lewy bodies. However, we have only scanty information on the immunoreactivity of alpha-synuclein in other inclusion bodies such as the Lewy body-like inclusions and the skein-like inclusions observed in motor neuron disease (MND). In this report, we immunocytochemically investigated inclusion bodies observed in the anterior horn neurons of the spinal cord in 29 patients with sporadic MND. Sixteen age-matched patients without any neurological disease served as controls. In MND patients, we recognized Lewy body-like hyaline inclusions, skein-like inclusions, Bunina bodies, basophilic inclusions, and intracytoplasmic hyaline (colloid) inclusions, but none of them were immunostained for alpha-synuclein. Our findings in this study do not support the hypothesis that MND could be classified as one of the diseases grouped as alpha-synucleinopathies.

Adult↗

PubMed2005

Parkin-mediated lysine 63-linked polyubiquitination: a link to protein inclusions formation in Parkinson's and other conformational diseases?

Most, if not all, neurodegenerative diseases are marked by the presence of ubiquitin-positive protein inclusions. How proteins within these inclusion bodies escape proteasomal degradation despite being enriched with ubiquitin remains a conundrum. Current evidence suggests a relationship between proteasomal impairment and inclusion formation, a persuasive explanation for the inability of the cell to remove ubiquitinated protein aggregates. Alternatively, the formation of ubiquitin-enriched inclusion may be uncoupled from the proteasome. Supporting this, we recently uncovered a novel, proteasomal-independent, catalytic activity for the Parkinson disease (PD)-linked ubiquitin ligase, parkin, that significantly enhances the formation of Lewy body (LB)-like inclusions generated in cultured cells by the co-expression of alpha-synuclein and synphilin-1. This unique activity of parkin mediates a non-classical, lysine (K) 63-linked ubiquitin multichain assembly on synphilin-1 that is distinct from the classical, degradation-associated, K48-linked ubiquitination. Interestingly, two other PD-linked gene products, alpha-synuclein and UCHL1, have recently also been associated with K63-linked ubiquitination. Inclusive of parkin, there are therefore now three PD-related gene products that are known to potentiate K63-linked ubiquitination, thus signalling an important functional relationship between this unique mode of ubiquitin tagging and PD pathogenesis. Mechanistically, the involvement of a "non-degradative" mode of ubiquitination in protein inclusion formation is an attractive explanation for how proteins are seemingly stabilized within inclusions.

Animals↗

PubMed1999

Formation of GFAP cytoplasmic inclusions in astrocytes and their disaggregation by alphaB-crystallin.

In several neuropathological conditions, alphaB-crystallin and glial fibrillary acidic protein (GFAP) accumulate and form cytoplasmic inclusions in astrocytes. To explore the pathogenesis of the inclusions and the possible functions of the accumulated alphaB-crystallin, GFAP and alphaB-crystallin were overexpressed in cultured astrocytes by transient transfection. Human GFAP formed filamentous, cytoplasmic inclusions in mouse astrocytes, NIH3T3 cells, rat C6 glioma cells, and human U251 glioma cells. These human GFAP inclusions did not contain the endogenous vimentin or beta-tubulin, and the intermediate filament and microtubular networks of the transfected cells appeared normal. alphaB-crystallin and hsp25 were associated with the GFAP inclusions. Increasing intracellular alphaB-crystallin levels using recombinant adenoviruses, either before or after GFAP inclusions were formed, decreased the number of inclusion-bearing astrocytes and converted the human GFAP from an inclusion to a spread, filamentous form. These results suggest that alphaB-crystallin reorganizes abnormal intermediate filament aggregates into the normal filamentous network.

3T3 Cells↗

PubMed2003

Proteasome inhibition induces inclusion bodies associated with intermediate filaments and fragmentation of the Golgi apparatus.

The ubiquitin-proteasome system is involved in a variety of biological processes. Inclusion bodies associated with intermediate filaments (IFs) and ubiquitin are observed in various diseases; however, the precise mechanisms of formation and the pathological significance of inclusion bodies have not been fully understood. We examined the effect of proteasome inhibitors on the structure of IF using anti-cytokeratin antibodies or transfection of green fluorescent protein-fused cytokeratin 18 in a hepatoma cell line, Huh7. Intracellular organelles were visualized by immunofluorescent and electron microscopies. Proteasome inhibitors induced IF inclusions associated with ubiquitin. Electron microscopic examination revealed inclusion bodies surrounded by filamentous structures. Autophagic vacuoles and lysosomes were frequently observed, and the organization of the Golgi apparatus was disrupted in these cells. After the removal of the proteasome inhibitors, the IF network and organization of the Golgi apparatus were restored. The IF inclusions could be induced by inhibition of the proteasome function. IF inclusions induced fragmentation of the Golgi apparatus and might inhibit the function of this important station of membrane traffic. The IF inclusions disappeared by restoring proteasome function, and autophagy and lysosomal degradation might be, at least in part, associated with the elimination of inclusion bodies.

Autophagy↗

PubMed2000

Asymmetrical temporal lobe atrophy with massive neuronal inclusions in multiple system atrophy.

This report concerns a rare association of asymmetrical temporal lobe atrophy with multiple system atrophy (MSA). A 53-year-old Japanese woman developed cerebellar ataxia and parkinsonism and was diagnosed as olivopontocerebellar atrophy (OPCA). This patient showed forgetfulness and subsequent disorientation even in the early stage of the disease. She fell into a decorticate state at the age of 64, and died a year later. The autopsy showed MSA with asymmetrical atrophy of temporal lobes, intraneuronal globular inclusions mostly confined to the hippocampus, amygdaloid nucleus, and most abundant in the granule cells in the dentate fascia. These inclusions were intensely argyrophilic and expressed marked immunoreactivity to ubiquitin, but not to neurofilament (NF), tau and paired helical filaments (PHF). Ultrastructurally, they were composed of scattered short filamentous structures of 15 to 30 nm in diameter, ribosome-like granules, mitochondria and lipofuscin. The lack of immunoreactivity against tau, NF and PHF suggests that the inclusions are distinct from Pick bodies. To our knowledge, MSA in association with asymmetrical temporal lobe atrophy with the present neuronal inclusions has not been reported. This case is distinct from MSA combined with atypical Pick's disease in the distribution and immunohistochemical properties of neuronal inclusions, and may present a new variant of MSA since the neuronal inclusions are similar, in many respects, to those of neuronal inclusions reported in MSA. Globular inclusions are also discussed in variants of Pick's disease, amyotrophic lateral sclerosis and Alzheimer's disease.

Atrophy↗

PubMed1983

Two types of paracrystalline inclusions in the Leydig cell of the Chinese hamster (Cricetulus griseus).

The ultrastructure of two types of paracrystalline inclusions is described, for the first time, in the Leydig cell of the Chinese hamster (Cricetulus griseus). The subunit of both types of inclusions consists of 5-nm-wide microfilaments differing only in the arrangement and shape of the microfilaments. The electron-dense microfilaments of the type A inclusion are usually in a serrated pattern with an equidistant 5-nm interval separating them. The type B inclusion has pairs of straight microfilaments separated by a 5-nm interval. Other microfilaments course at right angles to the paired units. Both types of inclusions are absent in the newborn, rarely found in the sexually immature, and commonly found in the sexually mature and aged animals. Both inclusions are found in the cytoplasm of Leydig cells, but only the A inclusion is found in the nucleoplasm. Their functional role is not yet determined, but the inclusions are commonly found in Leydig cells whose ultrastructural characteristics indicate normal steroidogenesis.

Aging↗

PubMed2003

Preliminary analysis of polyhydroxyalkanoate inclusions using atomic force microscopy.

Atomic force microscopy analysis of polyhydroxyalkanoate (PHA) inclusions isolated from sonicated Ralstonia eutropha cells revealed that they exhibit two types of surface structure and shape; rough and ovoid, or smooth and spherical. Smooth inclusions possessed linear surface structures that were in parallel arrays with 7-nm spacing. Occasionally, cracks or fissures could be seen on the surface of the rough inclusions, which allowed a measurement of approximately 4 nm for the thickness of the boundary layer. When the rough inclusions were imaged at higher resolution, globular structures, 35 nm in diameter, having a central pore could be seen. These globular structures were connected by a network of 4-nm-wide linear structures. When the inclusions were treated with sodium lauryl sulfate, the boundary layer of the inclusion deteriorated in a manner that would be consistent with a lipid envelope. When the boundary layer was largely gone, 35-nm globular disks could be imaged laying on the surface of the filter beside the inclusions. These data have facilitated the development of a preliminary model for PHA inclusion structure that is more advanced than previous models.

Cupriavidus necator↗

PubMed2000

Unique astrocytic inclusion in a 2 month-old baby showing Leigh-like brain lesions with lactic acidosis.

An unique cytoplasmic inclusion was found in astrocytes of a 2-month-old female baby who showed Leigh-like brain lesions with lactic acidosis, hypoglycemia and hepatomegaly. Although a defective enzyme was not determined, a metabolic disorder was suggested from clinicopathological observations. Symmetrically distributed lesions consisting of marked gliosis and proliferation of capillaries were observed in the basal ganglia, thalami and tegmentum. The astrocytic cytoplasmic inclusion was exclusively found in the cerebral and cerebellar white matter, where myelination was immature. The inclusion was round and eosinophilic, and positive for glial fibrillary acidic protein, vimentin, alphaB-crystallin, S-100 protein and microtubule associated protein 1B, immunohistochemically. An electron microscopic examination revealed an accumulation of intermediate filaments, ribosome and rough endoplasmic reticulum in the inclusion. The characteristic of this inclusion is different from that of other reported inclusions. The inclusion showed positive immunoreaction against CuZn superoxide dismutase, catalase, advanced glycation end-product and 4-hydroxy-2-nonenal antibodies, which suggest that oxidative stress is involved in the genesis of the inclusion.

Acidosis, Lactic↗

PubMed2000

Mitochondrial DNA variants in inclusion body myositis.

Mitochondrial DNA variants have been shown to be associated with many diseases. Mutations at mitochondrial DNA nucleotide positions 3192, 3196, 3397 and 4336 have been described in association with late-onset Alzheimer's disease. The pathological similarities between inclusion body myositis and Alzheimer's disease prompted an analysis of the relationship between the reported mutations and sporadic inclusion body myositis. The 4336G variant was not significantly increased in patients with inclusion body myositis or Alzheimer's disease when compared to controls. None of the patients with inclusion body myositis carried mutations at nucleotide positions 3192, 3196 and 3397. A transition at nucleotide position 4580 was detected in some patients with inclusion body myositis and Alzheimer's disease but was not significantly higher in frequency when compared to controls. Phylogenetic analysis showed that the 4336G and 4580A variants clustered together in their respective group. A group of patients with inclusion body myositis also clustered together on a separate branch of the phylogenetic tree. Closer investigation of this group revealed a common polymorphism at nucleotide position 16311. The frequency of the 16311C variant was higher in inclusion body myositis than in Alzheimer's disease and controls, although when only caucasian patients were considered the increased frequency was not statistically significant. Further studies will be required to determine whether this variant plays a role in the pathogenesis of inclusion body myositis.

Adult↗