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PubMed1976

Ultrastructural and x-ray analytical studies on intranuclear bismuth inclusions.

Parenteral administration of bismuth subnitrate produced intranuclear inclusions in the rabbit kidney tubules. In glutaraldehyde fixed material these inclusions had a homogeneous appearance but in osmicated material some of these inclusions showed a granular and fibrillar substructure. In relatively thick unstained sections prepared from unosmicated tissues, it was found that the inclusions were electron-dense, but they vanished from view when the electron beam was focussed on them. This phenomenon is thought to be due to the presence of bismuth, which is a mental with a high electrical resistance and low thermal conductivity. With the aid of electron-probe analysis the presence of bismuth was demonstrated in these inclusions and it seems possible that sulphur may be present here.

Animals↗
PubMed2000

NACP/alpha-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson's disease brains.

The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP), also called alpha-synuclein, is a major component of Lewy bodies in Parkinson's disease (PD) as well as of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. We previously reported argyrophilic, tau-negative glial inclusions in the midbrains of patients with PD and have now conducted immunocytochemical and ultrastructural examinations. The PD glial inclusions also are immunoreactive for NACP/alpha-synuclein, but not for beta-synuclein, and ultrastructurally are composed of filamentous structures about 25-40 nm in diameter. Double immunolabeling showed that the inclusions were present in both astrocytic and oligodendroglial cells. They were located within the substantia nigra in 13 of 30 patients with PD and outside the nigra in 24. The number of inclusions was correlated with the severity of nigral neuronal loss. These findings indicate that abnormal accumulation of NACP/alpha-synuclein in glial cells is a pathological feature of PD related to its progression.

Aged↗
PubMed1997

Localization and characterization of inclusion bodies in recombinant Escherichia coli cells overproducing penicillin G acylase.

Various concentrations of isopropyl beta-D-thiogalactopyranoside (IPTG) were used to induce production of the enzyme penicillin G acylase by recombinant Escherichia coli harboring plasmid pQEA11. The plasmid pQEA11 carries a wild-type pga gene, which is under the control of the tac promoter and lacIq. At low IPTG concentrations (0.025-0.1 mM), enzyme activity increased with increasing IPTG concentrations. At higher IPTG concentrations (0.2 and 0.5 mM), enzyme activity declined progressively. Examination of induced recombinant E. coli cells by transmission electron microscopy showed the presence of only periplasmic inclusion bodies at low IPTG concentrations (up to 0.1 mM) and both periplasmic and cytoplasmic inclusion bodies at high IPTG concentrations (0.2 mM and 0.5 mM). Results from sodium dodecyl sulfate/polyacrylamide gel electrophoresis and immunoblots of whole-cell proteins, membrane proteins and inclusion body proteins in these cells indicated that cytoplasmic inclusion bodies constituted an accumulation of preproenzyme (i.e., precursor polypeptide containing a signal peptide) and that periplasmic inclusion bodies constituted an accumulation of proenzyme (i.e., precursor polypeptide lacking a signal peptide).

Bacterial Proteins↗
PubMed2000

Spherical parasporal inclusions of the lepidoptera-specific and coleoptera-specific Bacillus thuringiensis strains: a comparative electron microscopic study.

Four Lepidoptera-specific Bacillus thuringiensis strains that belong to the four H serogroups (serovars sumiyoshiensis, fukuokaensis, darmstadiensis, and japonensis) and a Coleoptera (Scarabaeidae)-specific strain belonging to serovar japonensis were examined for comparative ultrastructure of spherical parasporal inclusions. The prominent feature of the inclusions of the Lepidoptera-specific strains was the existence of thick, highly electron-dense envelopes surrounding a homogeneous protein matrix. The envelopes were 15.0-66.7 nm thick and consisted of 5-12 layers of membrane. This is also the case with inclusions of a Coleoptera-specific strain. The ultrastructure of inclusions from the five strains was in marked contrast to that of the bipyramidal parasporal inclusions produced by a Lepidoptera-specific serovar sotto strain.

Animals↗
PubMed2005

[PM-Scl antibody positive systemic sclerosis associated with inclusion-body myositis].

We describe a 72- year-old patient with a ten year history of anti-PM-Scl positive systemic sclerosis associated with inclusion-body myositis. While the association of dermatomyositis and polymyositis with anti-PM-Scl positive systemic sclerosis is frequently reported, inclusion-body myositis was, to the best of our knowledge, only previously described once in association with anti-PM-Scl-positive systemic sclerosis. The distinction between inclusion-body myositis and other forms of inflammatory myopathy, like the histopathologically well distinguishable polymyositis or dermatomyositis, is relevant because of the poor response of inclusion- body myositis to immunosuppressive treatment. Our case underlines that in patients with anti-PM-Scl-positive systemic sclerosis and treatment resistant progressive myopathy the diagnosis of inclusion body myositis should be considered.

Aged↗
PubMed2002

Ubiquitin-positive neuronal and tau 2-positive glial inclusions in frontotemporal dementia of motor neuron type.

Attempts at classification of fronto-temporal dementias have not yet been completely successful. We report ten cases of sporadic fronto-temporal dementia (FTD) with ubiquitin-positive neuronal inclusions in cortex or in motor neurons in brain stem or spinal cord, which may contribute to the classification of FTD. Marked variation in clinical presentation as well as in pathological findings was the rule in all cases. Dementia was a prominent feature. Only one case had clinical features suggestive of motor neuron disease. Three of four younger onset cases displayed an especially severe atrophy of the temporal lobes, the basal ganglia and the substantia nigra. This contrasted with the other seven cases in which the fronto-temporal atrophy and changes in basal ganglia and substantia nigra were variable and sometimes mild. In addition to the presence of ubiquitin-reactive, but tau-and silver impregnation-negative neuronal inclusions, all cases demonstrated tau 2-positive glial inclusions, similar to those recently reported in three motor neuron disease cases with dementia. The glial inclusions were not visible with antibody to tau 1. Reaction with antibody to alpha-synuclein was invariably negative. If the combination of ubiquitin-positive neuronal and tau 2-positive glial inclusions is found to be consistently present in FTD of motor neuron type, this feature will provide a firmer basis for this diagnosis than previously available.

Adult↗
PubMed2005

Pediatric embryonal tumor of the cerebellum with rhabdoid cells and novel intracytoplasmic inclusions: distinction from atypical teratoid/rhabdoid tumor.

We report a case of embryonal tumor with novel inclusion bodies occurring in the cerebellum of a 12-year-old girl. The tumor was histopathologically composed of small undifferentiated cells intermingled with a small number of rhabdoid cells, which had an ultrastructural feature of intermediate filament whorls. Immunohistochemically, the neoplasm showed a polyphenotype, including glial fibrillary acidic protein (GFAP), S-100, synaptophysin, chromogranin A, cytokeratin, vimentin, smooth muscle actin, and desmin. However, epithelial membrane antigen (EMA) immunoreactivity was absent. The MIB-1 labeling index was high (25.6%). Ultrastructurally, there was no evidence of neuronal or myogenic differentiation. The small neoplastic cells contained numerous small intracytoplasmic inclusions stained pink by eosin and red by Masson's trichrome stain. The inclusion body was a densely packed, granulovesicular structure at the electron microscopic level, and was immunoreactive for vimentin, GFAP, desmin, and actin. Reverse transcription-PCR and immunohistochemistry showed the expression of INI1 at the RNA and protein levels, respectively. In conclusion, this tumor was differentiated from atypical teratoid/rhabdoid tumor by the absence of EMA and the presence of INI1 mRNA and protein, and diagnosed as an unclassified, embryonal tumor. Eosinophilic, granulovesicular inclusions of the tumor cells are novel cytoplasmic inclusions in the brain tumor.

Biomarkers, Tumor↗
PubMed1996

Comparative study of chronic aluminum-induced neurofilamentous aggregates with intracytoplasmic inclusions of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterized neuropathologically by chromatolysis, Bunina bodies, hyaline inclusions, skein-like inclusions and axonal spheroids. Aluminum, a known neurotoxin, is the cause of dialysis encephalopathy and is considered to be a causative agent in high incidence foci of ALS in the western Pacific. We have developed an experimental model of motor neuron degeneration in New Zealand white rabbits using chronic low-dose intracisternal administration of aluminum and compared the clinical and neuropathological changes to those of human ALS. Aluminum-inoculated rabbits developed progressive hyperreflexia, hypertonia, limb splaying, gait impairment, muscle wasting, hindlimb paralysis and impaired tonic immobility responses without overt encephalopathic features over a 14-month period. Examination of spinal cords from these animals demonstrated the frequent occurrence and progressive development of anterior horn cell lesions that included small, round, argentophilic perikaryal inclusions similar to hyaline inclusions seen in human ALS. Other inclusions were more condensed and eosinophilic, while still others had neurofibrillary tangle-like morphologies. Axonal spheroids and neuritic thickenings were also prominent and were identical to those seen in human ALS. We believe that the similar and progressive development of neuropathological changes observed in the chronic aluminum-intoxication model, compared to human ALS, warrants further study to aid in understanding the cellular and molecular mechanisms of human motor neuron disease.

Aluminum↗
PubMed1999

Astrocytic hyaline inclusions contain advanced glycation endproducts in familial amyotrophic lateral sclerosis with superoxide dismutase 1 gene mutation: immunohistochemical and immunoelectron microscopical analyses.

To clarify the neuropathological significance of the deposition of N(epsilon)-carboxymethyl lysine (CML), an advanced glycation endproduct, in astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis (FALS), autopsy specimens from five members of two different families who had the superoxide dismutase 1 (SOD1) gene mutations were analysed. Immunohistochemically, most of the neuronal and astrocytic hyaline inclusions were intensely stained by the antibody against CML. The distributions and intensities of the immunoreactivities for CML and SOD1 were similar in the inclusions in both cell types. Immunoelectron microscopy showed that both inclusions consisted of CML-positive granule-coated fibrils and granular materials. No significant CML or SOD1 immunoreactivity was observed in the neurons and astrocytes of the normal control subjects. Our results suggest that astrocytic hyaline inclusions contain CML and SOD1 in FALS patients with SOD1 gene mutations, and that the formation of CML-modified protein (probably CML-modified SOD1) is related to the cell degeneration.

Adult↗
PubMed2000

Glial intranuclear inclusion bodies in a patient with Alzheimer's disease.

We report a case of dementia in an elderly woman with the pathological findings of Alzheimer's disease and numerous intranuclear inclusions in astrocytes and occasionally in neurons. These inclusions were seen in the cerebral cortex, limbic areas, basal ganglia, thalamus, brain stem and cerebellum. They expressed ubiquitin and were ultrastructurally composed of haphazardly arranged straight filaments. The presence of similar intranuclear inclusions in previous cases of adult-onset dementia without other neuropathological changes suggests an important link between these kind of inclusions and dementia. To our knowledge, this type of intranuclear inclusions has not been previously described in association with Alzheimer pathology.

Aged↗
PubMed2001

Evidence for pathological involvement of the spinal cord in motor neuron disease-inclusion dementia.

Fronto-temporal dementia (FTD), characterised pathologically by ubiquitinated inclusions in the hippocampal dentate fascia and fronto-temporal cortex, may develop in association with motor neuron disease (MND). However, FTD with identical pathological hallmarks may occur in isolation and has been termed motor neuron disease-inclusion dementia (MND-ID). We studied the pathology of three cases of MND-ID including the spinal cord, which has not previously been examined in this condition. The ages of the patients at death were 53, 70 and 68 years and the onset of FTD 10, 15 and 9 years before death. Neuropathological findings in all cases included micro-vacuolation in cortical layer II and ubiquitinated intraneuronal inclusions in fronto-temporal cortex and hippocampal dentate fascia. One case showed unusual basophilic, ubiquitinated neuronal cytoplasmic inclusions in the brain stem. Qualitative assessment of the spinal cord was normal in two cases, while the third showed mild pallor of the lateral cortico-spinal tracts and ubiquitinated inclusions in motor neurons typical of MND. Morphometry did not reveal any significant loss or decrease in size of anterior horn motor neurons. The results of this study are consistent with the hypothesis that the pathological changes of pure MND and MND-ID form a spectrum and demonstrate that pathological involvement of the motor system may occur in MND-ID without clinical evidence of MND.

Aged↗
PubMed2003

Biological functions of the cytoplasmic TGBp1 inclusions of bamboo mosaic potexvirus.

The TGBp1 protein encoded by the first open reading frame of the triple-gene-block (TGB) of bamboo mosaic potexvirus (BaMV) plays important roles in virus movement; one of them is to shape the viral RNA before its being transported from cell to cell. However, TGBp1 mainly forms cytoplasmic inclusions which are devoid of the RNA-binding activity. With the purified TGBp1 inclusions of BaMV, we analyzed the possibility of dissociation of functional TGBp1 from the inclusions. Our data showed that the cytoplasmic inclusions were able to dissociate continuously functional TGBp1, which possessed ATP-binding, ATPase, and RNA-binding activities. Moreover, the dissociation of TGBp1 was significantly enhanced by the presence of viral RNA and capsid protein (CP), consistent with the finding that TGBp1 are able to form ribonucleoprotein complex with viral RNA and CP. Taken together, these results support the idea that the cytoplasmic TGBp1 inclusions are active pools of TGBp1, upon which viral RNA can be shaped into a transferable form.

Adenosine Triphosphatases↗
PubMed2006

Ultrastructural study of nuclear inclusions immunohistochemically positive for surfactant protein A in pulmonary adenocarcinoma with special reference to their morphogenesis.

To investigate the fine-structural nature of nuclear inclusions immunopositive for surfactant protein A (SP-A) antibody staining, a detailed ultrastructural study was performed, as well as immunohistochemical examination of pulmonary adenocarcinomas. Surgically resected tumor specimens from 31 patients were examined by immunohistochemistry focused on reactivity to SP-A and thyroid transcription factor 1 (TTF-1) antibodies. Only cases with >5% positive nuclear inclusions in cancer cells were considered positive, some of which were examined by electron microscopy. Immunohistochemically, 6 of 31 cases were doubly positive for SP-A and TTF-1 antibodies. On electron microscopy, SP-A-positive nuclei contained diffuse or globular fine granular substance as inclusions. Both types of globular and diffuse inclusions were sometimes connected to the inner nuclear membrane, in association with fragmented or stacked membranous structures. The findings of this study suggested that nuclear inclusions positive for SP-A antibody staining in adenocarcinomas of the lung were derived from accumulated content in the perinuclear cistern resembling pseudoinclusion processes and composed of proteins antigenically cross-reactive with SP-A.

Adenocarcinoma↗
PubMed1986

Ultrastructural morphology of thalamic cytoplasmic inclusion bodies in El mouse.

The established hereditary El mouse, clinically characterized by intermittent seizures of the grand mal type, has been investigated mainly from biochemical or electrophysiologic points of view. The present paper provides morphologic details on neuronal inclusion bodies occurring in the thalamus of the El mouse. Numerous intracytoplasmic inclusion bodies, 1 to 10 microns in diameter, were observed in the thalamic neuronal cells even in the young or seizure-free El mouse. Although such inclusion bodies were also studied in aging normal mice, their number in the El mouse was significantly higher than the number seen in aged mice. In addition to the thalamic inclusions, there were other changes observed, such as hippocampal neuronal loss and ischemic or chromatolytic neurons in the temporal cortex. We suggest that the neuronal changes in hippocampus and cortex were not primary to the El mouse epileptogenesis. We discuss the correlation between thalamic neuronal inclusions and convulsive seizures in the El mouse.

Animals↗
PubMed1981

Morphology and distribution of cytoplasmic inclusions in adrenoleukodystrophy.

We report some additional observations on the pathognomonic cytoplasmic inclusions in a typical case of adrenoleukodystrophy (ALD). Study of the linear inclusions by means of tilt-stage electron microscopy indicated that they represent trilaminar sheet-like structures distinct from materials seen in various other storage disorders. This study emphasizes that the inclusions in the adrenal and testicular parenchymal cells morphologically differ from those in the brain macrophages. In the latter they occur as membrane-bound discrete structures while in the parenchymal cells they are always seen lying free in the cytoplasm and associated with cleft-like spaces. This morphologic variation of the inclusions is noteworthy and probably reflects a biochemical difference in the storage materials in these two most severely affected organs. In addition, this study demonstrates the presence of linear inclusions within macrophages in otherwise normal-appearing liver, spleen, thymus and also in the renal tubular cells. These findings suggest that the abnormal materials containing very long chain fatty acids enter the blood stream and become sequestered in the reticuloendothelial system and possibly are also excreted in the urine. Detection of these abnormal fatty acids in blood and urine may simplify diagnosis of ALD.

Adolescent↗
PubMed1975

Intranuclear inclusions in mammotrophs of the Mongolian gerbil: effect of low doses of estradiol benzoate and a study of females before weaning.

The effect of dose of estrogen on induction of intranuclear inclusions was studied in mammotrophs of the Mongolian gerbil. The number of inclusions per high power field increased significantly with 0-5 and 1-0 mug/day of estradiol benzoate but not with the 0-05 mug dose. A form of inclusion was seen in young female gerbils before weaning which suggests that inclusions arise from the cytoplasm. Intranuclear inclusions develop soon after weaning of gerbils (0-06 +/- 0-01 vs. 0-19 +/- 0-03 for young mature females).

Animals↗
PubMed1991

Inclusion body myositis and paramyxoviruses.

Inclusion body myositis (IBM) is a distinct type of muscle disease. The characteristic electron microscopic findings, intranuclear or intracytoplasmic inclusions composed of microtubular filaments, morphologically resemble paramyxovirus nucleocapsids. These findings and the reported immunoreactivity of the inclusions with mumps virus antibodies have suggested that inclusion body myositis is a chronic virus infection. We analyzed skeletal muscle specimens from three patients with characteristic light microscopic features and electron microscopically verified inclusions of IBM by immunocytochemistry using antibodies raised against members of the paramyxovirus group, and by in situ hybridization with a cRNA probe representing the mumps virus nucleocapsid gene. The specificity of the reactions was demonstrated with infected and uninfected cultured cells. No immunocytochemical staining or hybridization signal was observed in biopsy specimens from IBM patients. These findings speak against a paramyxovirus etiology of IBM.

Aged↗
PubMed1993

The value of polyclonal carcinoembryonic antigen immunostaining in the diagnosis of microvillous inclusion disease.

Microvillous inclusion disease is a specific disorder recognized as a cause of intractable diarrhea of infancy. We studied three cases by light microscopy, electron microscopy, and immunostaining for polyclonal carcinoembryonic antigen (CEA). Histologically, all cases had villous atrophy and abnormal accumulation of periodic acid-Schiff-positive material in surface enterocytes. Ultrastructurally, poorly developed brush-border and intracytoplasmic inclusions lined by intact microvilli were present in surface enterocytes. Crypt cells showed well-preserved surface microvilli. Carcinoembryonic antigen immunostaining showed prominent intracytoplasmic reactivity in surface enterocytes and linear brush-border reactivity in crypt cells. Normal and diseased small bowel biopsy specimens used as controls revealed linear brush-border reactivity without intracytoplasmic staining. Intracytoplasmic positivity for carcinoembryonic antigen in microvillous inclusion disease is explained by its presence in the glycocalyx within the microvillous inclusions. The demonstration of a distinct staining pattern for polyclonal carcinoembryonic antigen in routinely processed small bowel biopsy specimens provides a new useful criterion that complements other established techniques for accurate diagnosis of microvillous inclusion disease.

Antibodies↗