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Tubule-containing inclusions in the epithelial cells of the mouse epididymal duct.

The mouse epididymis, consisting of a head, body and tail, was examined by electron microscopy. The principal cells of the epididymal duct in the epididymal body have rod-shaped inclusions, 0.3 to 1.0 microns in diameter and 2 to 5 microns in height. The inclusions contain a bundle of tubules, about 40 nm in diameter, with a wall about 6 nm in thickness. The tubules are regularly arranged in a hexagonal pattern. A goniometric study of the inclusions shows evidence that the wall of the tubules consists of filament-like subunits which run parallel to each other and are inclined at about 25 degrees to the axis of the tubules, forming loose spirals. The inclusions occasionally contain material similar to that in the lysosomal bodies. These inclusions were observed in every epididymis examined, and seem to be related to the specific functions of the principal cells in the epididymal body.

Animals↗

Shape variation of bilayer membrane daughter vesicles induced by anisotropic membrane inclusions.

A theoretical model of a two-component bilayer membrane was used in order to describe the influence of anisotropic membrane inclusions on shapes of membrane daughter micro and nano vesicles. It was shown that for weakly anisotropic inclusions the stable vesicle shapes are only slightly out-of-round. In contrast, for strongly anisotropic inclusions the stable vesicle shapes may significantly differ from spheres, i.e. they have a flattened oblate shape at small numbers of inclusions in the membrane, and an elongated cigar-like prolate shape at high numbers of inclusions in the vesicle membrane.

Anisotropy↗

Demyelinative process associated with atypical intranuclear glial inclusions.

This case study documents a demyelinating process associated with atypical glial intranuclear inclusions. The patient, a 38-year-old woman, presented with acute onset of headaches and weakness. Magnetic resonance imaging revealed two discrete intrahemispheric lesions. Light microscopic examination showed small, homogeneous, eosinophilic inclusions chiefly in astroglial nuclei. By electron microscopy these inclusions were shown to be clusters of filamentous structures. Attempts to identify the particles with an antibody to measles virus and in situ hybridization to JC virus were negative. The morphologic appearance of the inclusions in this case is similar to that described in neuronal intranuclear inclusion disease.

Adult↗

[Benign epithelial inclusions in pelvic lymph nodes. 2 case reports].

A large number of lymph node inclusions excluding endometriosis have been described in a variety of anatomical sites; they are usually epithelial and only rarely non-epithelial. Their presence can give rise to an erroneous diagnosis of metastasis. Recently the staging laparotomy has become a frequent procedure in the management of neoplasms of the female genital tract, and involves abdominal lymphadenectomy, inspection of the peritoneal surface, multiple biopsies and the resection of suspicious lesions. During the surgery, and among the lesions excised, the occasional presence of lymph node inclusions can lead to a diagnostic error. In order to avoid this problem, it is necessary to be adequately informed about these inclusions, including their anatomic sites, their histologic characteristics and the knowledge that they can present in lymph nodes related to an inflammatory process or a tumour. This revision is to alert pathologist towards a group of lesions which can imitate metastatic carcinoma, and specially towards those inclusions which present together with malignant neoplasias of the female genital tract. Recently we received two cases of pelvic lymph nodes, initially diagnosed as metastatic carcinoma, and eventually found to correspond to mesothelial cell hyperplasia in one case, and to lymph node inclusions in the other.

Adult↗

Mesothelial paracrystalline inclusions in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: Uremia is known to be followed by changes in the serous membranes of pleura, pericardium, and peritoneum. During continuous ambulatory peritoneal dialysis (CAPD), the peritoneum is exposed to altered body conditions as well as to the influence of dialysate. The aim of the present study was to examine the ultrastructure of the mesothelial cells in CAPD patients, and to compare the findings with those from studies of the peritoneum in uremic controls. Paracrystalline intracytoplasmic inclusions in mesothelial cells were objects of special interest. METHODS: Biopsies of human parietal peritoneum were studied. These were taken from 12 uremic patients during catheter implantation before the start of CAPD, and from 7 CAPD patients during catheter removal for infection or malfunction. The samples were prepared in the standard way to be studied by transmission electron microscopy (TEM). RESULTS: Paracrystalline intracytoplasmic inclusions were seen in mesothelial cells only by TEM. They appear as filamentous structures at the outer part of the inclusions, and as pearl-like structures at the core of the inclusions. Sacculate dilatations of rough endoplasmic reticulum cisternae with partly destroyed membranes and only few ribosomes were also seen, with and without densely osmiophilic filaments within the cisternae. We have found paracrystalline intracytoplasmic inclusions in mesothelial cells from uremic and CAPD patients both. According to the literature, these changes are present in one third of biopsies from uremic patients. Until now, however, they have not been mentioned in CAPD patients.

Crystallization↗

[Oligodendroglial inclusions, a marker of multisystemic atrophies].

Nine cases of multiple system atrophy and 1 case of autosomal dominant olivopontocerebellar atrophy (neuropathological diagnosis) were retrospectively examined for the presence of oligodendroglial inclusions. Clinical diagnosis in the first 9 cases had been: olivopontocerebellar atrophy (3 cases), atypical Parkinson's disease (2 cases), Shy-Drager syndrome (2 cases) and multiple system atrophy (1 case); one of the patients could not be included in any of the above mentioned groups. The oligodendroglial inclusions were argyrophilic and located in the cytoplasm around the nucleus. They were revealed by Bodian's method in all cases of multiple system atrophy. They were not found in the case of autosomal dominant olivopontocerebellar atrophy. They were labelled by anti-ubiquitin antibodies, and were negative with anti-tau antibodies. At electron microscopy, they consisted of rectilinear profiles coated with a fuzzy material (diameter: 20-33 nm); this aspect was compatible with microtubules. Oligodendroglial inclusions were prominent in regions selectively vulnerable in multiple system atrophy (tegmentum pontis, putamen, inferior olives, substantia nigra and cerebellar white matter), even in those areas where neuronal loss or fascicular atrophy were minimal or absent. They were also observed in regions considered to be spared in multiple system atrophy, such as the motor cortex and the corpus callosum. Argyrophilic oligodendroglial inclusions are an early and specific marker of multiple system atrophy. It is suggested that autosomal dominant olivopontocerebellar atrophy lacking oligodendroglial inclusions does not belong to multiple system atrophy.

Adult↗

Fine structure and biochemical mechanisms underlying nigrostriatal inclusions and cell death after proteasome inhibition.

Mutation of genes encoding for various components of a metabolic pathway named the ubiquitin-proteasome system (UP) leads to inherited forms of Parkinson's disease (PD), whereas various components of the UP are constantly present within neuronal inclusions, Lewy bodies, that characterize most genetic and sporadic forms of PD. It has been hypothesized that impairment of this metabolic pathway might be a common mechanism for the onset of PD, and a recent study demonstrated a dysfunction of the UP system within the substantia nigra of patients affected by sporadic PD. In search for the mechanisms underlying the selective toxicity for nigral neurons after inhibition of the UP system, we explored the selective effects after striatal microinfusions of lactacystin or epoxomycin and potential retrograde changes within the ipsilateral substantia nigra. We found that neurotoxicity was selective for striatal dopamine (DA) components and led to retrograde apoptosis within nigral DA cells, which developed neuronal inclusions staining for antigens of the UP system. We found the same ultrastructural features characterizing inclusions obtained in vivo and in vitro after UP inhibition. In vivo, lactacystin-epoxomycin-induced toxicity was suppressed by inhibiting DA synthesis. Similarly, in vitro inclusions and apoptosis were prevented by reducing endogenous DA. On the other hand, toxicity of proteasome inhibition was enhanced by drugs augmenting DA availability: l-3,4-dihydroxyphenylalanine, monoamine oxidase blockers, and DA beta-hydroxylase blockers. These findings demonstrate that impairment of the UP system produces cell death and neuronal inclusions selectively for DA-containing neurons that depend on the occurrence of endogenous DA.

3,4-Dihydroxyphenylacetic Acid↗

Neurofilament inclusion body disease with early onset frontotemporal dementia and primary lateral sclerosis.

A small number of patients have recently been described with a sporadic neurodegenerative disease, associated with the neuropathological finding of neurofilament-immunoreactive neuronal inclusions. The clinical and pathological spectrum of this new disease entity has yet to be fully defined. We describe an additional case of "neurofilament inclusion body disease" (NIBD) with several unusual features. This young woman, who suffered from rapidly progressive frontotemporal dementia (FTD) and features of primary lateral sclerosis (PLS), died at age 29. Neuropathological examination disclosed numerous neuronal cytoplasmic inclusions in many regions of the central nervous system. The inclusions varied in morphology with some being immunoreactive for ubiquitin while others showed strong positivity for neurofilament proteins. Intranuclear neuronal inclusions were also present. There was no significant tau or alpha-synuclein pathology. There was severe degeneration of the corticospinal tracts but lower motor neurons were normal in number and morphology. This case confirms that NIBD should be considered in the differential diagnosis of FTD, particularly in young patients. In addition, it extends the clinical phenotype of NIBD to include PLS and better defines the anatomical distribution and morphology of the pathological lesions.

Adult↗

Inclusion proteins of Chlamydiaceae.

Chlamydiaceae are obligate intracellular pathogens with family members among the etiological agents of several human diseases, such as blinding trachoma, sexually transmitted disease (Chlamydia trachomatis) and pneumonia (Chlamydophila pneumoniae, Chlamydophila psittaci). The bacteria replicate intracellularly in a membrane-bound vacuole termed inclusion. The chlamydial inclusion is effectively separated from eukaryotic endocytic pathways. More than two decades ago it was already speculated that Chlamydiae might modify the inclusion membrane through the insertion of chlamydial-derived components. However, because the classical genetic approaches cannot be applied to manipulate these bacteria, it took more than 10 years before definitive proof was obtained that Chlamydiae indeed actively modify the inclusion membrane by the insertion of proteins of chlamydial origin, first observed by Rockey et al. in 1995. This review will focus on the structural and functional aspects of inclusion proteins of Chlamydiaceae, thereby summarizing data obtained by in vitro studies and comparative genomics.

Bacterial Proteins↗

Crystalline muscle inclusions in atypical postinfectious polyradiculoneuropathy.

Crystalline inclusions were found in the muscle of a previously healthy 63 year old male with atypical postinfectious polyradiculoneuropathy. Approximately 12 days after the onset of the illness, biopsy of biceps femoris and vastus lateralis muscles revealed, in addition to changes consistent with early neurogenic atrophy, inclusions measuring 22 micronm in greatest dimensions. In plastic-embedded toluidine blue stained sections the translucent ovoid to angular inclusions were seen in a subsarcolemmal position, adjacent to nuclei. Ultrastructural examination revealed a crystalline structure consisting of parallel dense lines measuring approximately 70 A in diameter with an axial periodicity of 130 A. Unlike rods, the crystalline inclusions were not continuous with Z-discs; rather they displaced contractile and other cellular elements. Their appearance was similar to intramuscular crystals in diabetic amyotrophy and to vincristine-induced and naturally occurring intracytoplasmic crystalline structures. The nature of the crystalline inclusions and their relationship to the basic disease process was not established.

Crystallization↗

The occurrence of beta-glucuronidase in erythrocyte inclusions.

This study presents erythrocytic inclusion bodies exhibiting histochemically a strong beta-glucuronidase activity. The unique occurrence of this enzyme in cells of the erythropoietic series has never been described before and characterizes a novel type of erythrocyte inclusions mainly observed in patients suffering from liver damage but also from myelodysplasia and congenital dyserythropoietic anemia type I. Since it is known that hepatocytes contain high activities of beta-glucuronidase, we supposed a relationship between an increased breakdown of liver cells and the appearance of beta-glucuronidase positive inclusions in the red cells. To prove this hypothesis, we determined the beta-glucuronidase plasma levels of 99 unselected patients suffering from various liver disorders in comparison with 19 healthy controls by use of the umbelliferone technique. Our results indicate that in cases with liver diseases beta-glucuronidase plasma levels are significantly increased as compared with normal persons. The availability of a sufficient amount of beta-glucuronidase, thus, seems to be one prerequisite for the appearance of these inclusions in erythrocytes. As demonstrated by our investigations on congenital dyserythropoietic anemia, in which the red cells also show beta-glucuronidase positive inclusions, another premise seems to be an elevated autophagolysosomal activity in the erythrocytes.

Adult↗

Paracrystalline inclusions in various isolates of the blue-green bacteria Nostoc and Anabaena.

A number of different crystalline inclusions were observed in various isolates of Anabaena and Nostoc. Membrane-limited crystalline bodies were observed in 7 of 20 isolates of Anabaena and 19 of 29 isolates of Nostoc. These are spherical, single membrane-limited bodies from 0.6 to 0.1 micron in diameter. In most of the isolates they contained needle-like crystals 20 A in thickness and up to 80 nm in length. In 9 of the isolates the inclusions contained granular and fibrillar material. The number of bodies per cell varied in the different isolates from only a few, observed in many sections, up to 5 in a single section of A. subtropica (B1618). Crystalloids were observed in the cytoplasm of Anabaena sp. (1551), N. calcicola (B382), Nostoc sp. (588), and N. punctiforme (1629). In Anabaena sp. (1551) the roughly cuboidal inclusions 0.6 micron in diameter were composed of 100 A thick osmiophilic striations spaced to produce a 150 A periodicity. In Nostoc sp. (588) the elongate, 0.1 micron by 2.5 micron, crystalloids were composed of 100 A thick osmiophilic striations spaced to produce a 200 A periodicity. N. punctiforme (1629) and N. calciola (B382) contained intrathylakoidal crystalloids which consisted of short curved segments with 100 A thick osmiophilic striations producing a 200 A periodicity. Granular areas were observed in 2 isolates of Anabaena and 5 of Nostoc. These bodies found in various locations in the cells, were interpreted to be elongate structures 0.2 micron thick, 1.2 micron long and about 5 micron in depth. These inclusions were composed of 15 nm diameter granules which in some section planes appeared in rows spaced 20 nm apart. Spherical bodies up to 0.7 micron in diameter and of medium electron density were observed in 4 isolates of Anabaena and 2 of Nostoc. Convoluted inclusions were found in N. calcicola (B382) and Anabaena sp. (1551). These roughly spherical bodies up to 0.8 micron in diameter contain lighter swirled areas.

Crystallization↗

Neuronal intranuclear hyaline inclusion disease associated with premature coronary atherosclerosis.

Neuronal intranuclear hyaline inclusion disease (NIHID) has been recognized in 14 patients. It usually occurs in the first and second decades but has been seen in the sixth. Both sexes are affected by this sporadic multisystem degenerative disorder that has involved the central and peripheral nervous systems with fibrillar and granular intranuclear inclusions. NIHID appears to be several variants of a multisystem degenerative disease as illustrated by the combination of a spontaneous, degenerative central and peripheral nervous system disorder with neuronal intranuclear inclusions and severe atherosclerotic coronary artery disease in a 23-year-old white man. Beginning at 11 years of age, this patient had experienced diffuse muscle spasms, dysarthria, dysphagia, tremors, ataxia, oculogyric crises, progressive muscle weakness, and atrophy. At autopsy, neuronal intranuclear hyaline inclusions and neuronal loss were seen in his brain, brainstem, cerebellum, spinal cord, bowel, bladder, and esophagus. These fibrillary and granular Cowdry type A and B intraneuronal inclusions were consistent with the diagnosis of NIHID associated with severe coronary atherosclerosis.

Adult↗

Occurrence of intracytoplasmic inclusion bodies in the digestive epithelium of fallow deer (Dama dama L).

Intracytoplasmic inclusion bodies were observed in the digestive epithelium of fallow deer (Dama dama L) suffering from bovine virus diarrhea/mucosal disease. Similar inclusion bodies were also found in the ruminal epithelium of fallow deer subjected to overfeeding by supplementary food. Inclusion bodies were not found in the upper alimentary mucosa of clinically healthy deer but were frequently found when these tissues were subjected to autolysis. At electron microscopical studies the inclusion bodies were found to consist of granular protein-like material encircled by a single membrane. Such inclusion bodies may constitute a non-specific degenerative cell response which could be elicited by diverse factors including autolysis.

Animals↗

The significance of müllerian inclusions found at second-look laparotomy in patients with epithelial ovarian neoplasms.

When no visible tumor is identified at second-look laparotomy, selected biopsy specimens or cytologic washings may reveal microscopic tumor or benign pathologic atypia. The pathology material from 311 patients with epithelial ovarian carcinoma who had no macroscopic tumor at second-look laparotomy was evaluated for psammoma bodies, müllerian inclusions (benign glandular inclusions), microscopic tumor, and either inflammation or fibrosis. Progression-free intervals and survival rates were influenced by the presence of müllerian inclusions (favorably), tumor or positive cytology (unfavorably), and inflammation or fibrosis (unfavorably). Multivariate analysis (proportional hazards model) demonstrated that both the progression-free interval and survival rates were influenced significantly by the presence of microscopic tumor and tumor grade. Of 51 patients with müllerian inclusions and no microscopic tumor, 23 received additional treatment after second-look laparotomy. No differences were noted in the progression-free interval or survival rates when these patients were compared with the 28 nontreated patients. Of the treated patients, three died from chemotherapy toxicity, whereas there were no chemotherapy-related deaths in the nontreated group. These findings indicate that the presence of müllerian inclusions at second-look laparotomy does not justify treatment, and that further treatment after misinterpretation of these benign pathologic entities may lead to harmful results.

Antineoplastic Agents↗

Isolated cilia and crystalloid inclusions in murine bone marrow stromal cells.

Bone marrow stromal cells, especially reticular cells and macrophages, are thought to have important functions in the hematopoietic inductive microenvironment (HIM). In order to define the details of their fine structure, the femoral bone marrow of 50 C 57 BL mice was examined by electron microscopy after fixation by vascular perfusion. Almost all the structures of the murine bone marrow stromal cells were similar to those previously reported. Murine bone marrow reticular cells had some isolated cilia (with a frequency of 6.0%) of 9 + 0 pattern in their axoneme. The murine bone marrow macrophages had crystalloid inclusions (CI) that revealed characteristic periodic substructure. These periodic structures could be classified into four types (types A-D). Type A inclusions had a rather amorphous structure and were the most common (with a frequency of 61.9%). Type B inclusions had a periodic lamellar structure oblique to the long axis of the CI itself at intervals of about 3.5 nm. Type C inclusions had a periodic lattice structure at intervals of about 3.7 nm, and were the least frequent (with a frequency of 6.0%). Type D inclusions had periodic laminated structure parallel to the long axis of CI at intervals of about 3.5 nm. Although the true significance of isolated cilia of murine bone marrow reticular cells and the periodic internal structures of CI in murine bone marrow macrophages remains unknown, they must not be ignored as only incidental findings: they may be useful to the understanding of the relationship between function and structure in future research on HIM.

Animals↗

Presence of intranuclear inclusions in the principal cells of the epididymis of the garden dormouse Eliomys quercinus L.

Globular inclusions are present in the nuclei of the columnar epithelial cells lining the ductus epididymidis in the garden dormouse, Eliomys quercinus L. Such inclusions have been reported in the dog where they are very abundant, in the stallion and in man. They have been found to be absent from sheep, cat, rabbit, guinea pig, rat and mouse. We have now found them in the garden dormouse, an ascrotal hibernator, but have been unable to detect them in another hibernator, the thirteen-lined ground squirrel Citellus tridecemlineatus, this time a scrotal mammal. The globular inclusions are first seen in the perinuclear space formed by the two membranes of the nuclear envelope; they are then invested by the inner membrane of the nuclear envelope and transferred into the nucleus. They later disintegrate and the vacuole is finally left with an electron-transparent content. The number of inclusions varies with the hormonal status of the animal: the granules are always present as soon as there is a rise in plasma testosterone. Electron energy-loss spectroscopy in the electron microscope (EELS) shows that inclusions contain C, N, O, Fe, Mg, P and S. This suggests that the intranuclear granules are made of protein cross-linked by disulphur bonds and contain iron, magnesium and phosphorus.

Animals↗

Intranuclear helioid inclusions.

We have coined the term 'helioid inclusion' to describe a new type of single-membrane-bound intranuclear inclusion which contains one or more rounded bodies with radiating filaments (helioid bodies). Helioid bodies were not found in the rough endoplasmic reticulum in the cytoplasm, or in the cytoplasmic matrix, but a helioid body was seen in dilated rough endoplasmic reticulum included in a double-membrane-bound intranuclear pseudoinclusion. No firm conclusion regarding the genesis of helioid inclusions has emerged from our studies, but two possibilities exist: 1) that helioid bodies derive from modification of serous secretory granules sequestrated in an intranuclear inclusion; or 2) that they develop by condensation of the contents of the perinuclear cistern or rough endoplasmic reticulum subsequent to its sequestration in an intranuclear inclusion.

Adenoma↗