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Unusual nuclear inclusions in four nerve biopsies. An ultrastructural study.

The authors have reported four cases where the study of peripheral nerve biopsy revealed the presence of abnormal cells in the endoneurial space. Their bulky nuclei contain in fact numerous deposits more or less tubular reminiscent of the intranuclear structures observed in the multiple sclerosis brains, and other very rare diseases. Exceptionally it seems have these images been described in peripheral nerves. It must be stressed that only one patient had an inflammatory type disease. The meaning of these images is discussed, though no definite conclusion could be reached.

Aged↗

Paracrystalline structures in the epithelial principal cells of the epididymis of water buffalo (Bubalus bubalis).

The ultrastructure of many principal cells in the cauda epididymis of water buffaloes with ages varying between 4, 18, 24, 30 and 36 months, revealed, in many cells, the presence of long, curved paracrystalline structures that are quite large and frequently encountered in the cytoplasm, usually near the nucleus. Concomitantly or not, smaller rod-like, hexagonal or curled structures can be found in the nucleus. Both structures, cytoplasmic and intranuclear, are made up of a sheath of parallel filaments. These paracrystals may appear as thin, regularly spaced filaments that are associated with fine, evenly spaced subunits. Occasionally, the association of paracrystalline structures with membranes similar to the endoplasmic reticulum was observed, but no membranes were consistently found in close contact with the nuclear crystalloids. It is postulated that both structures are proteinaceous and may represent stored enzymes or substances present in the intraluminal fluid, which are absorbed and initially stored in numerous intraepithelial vacuoles of the corpus and cauda of the buffalo epididymis.

Animals↗

Mitosis in the fission yeast Schizosaccharomyces pombe as revealed by freeze-substitution electron microscopy.

Nuclear division in Schizosaccharomyces pombe has been studied in transmission electron micrographs of sections of cells fixed by a method of freeze-substitution. We have found cytoplasmic microtubules in the vicinity of the spindle pole bodies and two kinds of microtubules, short discontinuous ones and long, parallel ones in the intranuclear mitotic spindle. For most of the time taken by nuclear division the spindle pole bodies face each other squarely across the nuclear space but early in mitosis they briefly appear twisted out of alignment with each other, thereby imparting a sigmoidal shape to the bundle of spindle microtubules extending between them. This configuration is interpreted as indicating active participation of the spindle in the initial elongation of the dividing nucleus. It is proposed that mitosis is accompanied by the shortening of chromosomal microtubules simultaneously with the elongation of the central pole-to-pole bundle of microtubules of the intranuclear spindle. Daughter nuclei are separated by the sliding apart of interdigitating microtubules of the spindle at telophase. Some of the latter bear dense knobs at their ends.

Cell Nucleus↗

Functional role of intrahypothalamic release of oxytocin and vasopressin: consequences and controversies.

This brief review of vasopressin (VP) and oxytocin (OT) release into the extracellular space of the supraoptic (SON) and paraventricular (PVN) nuclei focuses on recent data illustrating the significance of their intranuclear release and the potential functional consequences. With the use of in vitro techniques, it has been demonstrated that administration of exogenous OT causes local peptide release and that, in vivo, this facilitates the milk ejection reflex. These findings lead to the idea that endogenous peptides are released into the hypothalamic nuclei. Microperfusion techniques have been used to monitor the dynamics of intranuclear OT and VP release in response to distinct stimuli. It is clear that intranuclear release of OT plays a role during reproductive states (parturition and lactation) and that intranuclear release of VP and OT is involved in osmoregulation. This review discusses 1) the origin of the intranuclearly released peptides, 2) stimuli which cause release into the hypothalamic nuclei, and 3) the function of intranuclear VP and OT, e.g., regulation of local morphology, feedback mechanisms and synchronization, and the possible role in regulating autonomic function and behavior.

Animals↗

Intranuclear inclusions in a myopathy of late onset.

Filamentous intranuclear inclusions in a case of myopathy of late onset are described. The filaments were usually in parallel array although occasionally they were haphazardly arranged in bundles ranging up to 5 mu in length. The filaments were approximately 120 A in diameter and were separated by a space measuring 180-220 A. Possible explanations of their occurrence in the nucleoplasm are discussed, including possible origin from the cytoplasm as a result of invagination of nuclear membrane and intranuclear entrapment of myofibrils from the cytoplasm. Their appearance does not suggest any recognizable structure such as myofilaments or virus. It is possible that the filaments are protein newly synthesized as a direct result of virus infection with invasion of the nuclei of the muscle cell.

Aged↗

Egress of alphaherpesviruses: comparative ultrastructural study.

Egress of four important alphaherpesviruses, equine herpesvirus 1 (EHV-1), herpes simplex virus type 1 (HSV-1), infectious laryngotracheitis virus (ILTV), and pseudorabies virus (PrV), was investigated by electron microscopy of infected cell lines of different origins. In all virus-cell systems analyzed, similar observations were made concerning the different stages of virion morphogenesis. After intranuclear assembly, nucleocapsids bud at the inner leaflet of the nuclear membrane, resulting in enveloped particles in the perinuclear space that contain a sharply bordered rim of tegument and a smooth envelope surface. Egress from the perinuclear cisterna primarily occurs by fusion of the primary envelope with the outer leaflet of the nuclear membrane, which has been visualized for HSV-1 and EHV-1 for the first time. The resulting intracytoplasmic naked nucleocapsids are enveloped at membranes of the trans-Golgi network (TGN), as shown by immunogold labeling with a TGN-specific antiserum. Virions containing their final envelope differ in morphology from particles within the perinuclear cisterna by visible surface projections and a diffuse tegument. Particularly striking was the addition of a large amount of tegument material to ILTV capsids in the cytoplasm. Extracellular virions were morphologically identical to virions within Golgi-derived vesicles, but distinct from virions in the perinuclear space. Studies with gB- and gH-deleted PrV mutants indicated that these two glycoproteins, which are essential for virus entry and direct cell-to-cell spread, are dispensable for egress. Taken together, our studies indicate that the deenvelopment-reenvelopment process of herpesvirus maturation also occurs in EHV-1, HSV-1, and ILTV and that membrane fusion processes occurring during egress are substantially different from those during entry and direct viral cell-to-cell spread.

Alphaherpesvirinae↗

Pseudorabies in a dog.

Pseudorabies was diagnosed in a 5-year-old female crossbred dog by histologic examination and virus isolation. The clinical signs were depression, salivation, head pressing, and emesis. There were no gross pathologic findings. The microscopic findings in the brain stem consisted of mononuclear cell infiltrates in the leptomeninges, subarachnoid space, and neuropil. In addition, there were mononuclear cell perivascular cuffs, focal areas of gliosis, neuronal degeneration, and acidophilic intranuclear inclusions in neurons and astrocytes. Other microscopic findings were edema of lungs and fatty change in the liver. The virus was isolated from the brain and tonsils and identified by fluorescent antibody technique. Pseudorabies virus was isolated from pigs on the farm.

Animals↗

Putative site for the acquisition of human herpesvirus 6 virion tegument.

The virion of human herpesvirus 6 (HHV-6) contains a very distinct tegument layer, occupying the space between the nucleocapsid and the virion envelope. Ultrastructural analyses of thymocytes infected with HHV-6 revealed the presence of intranuclear spherical compartments, approximately 1.5 microns in diameter, in which tegumentation seems to take place. These compartments, termed tegusomes, were bounded by two membranes and contained ribosomes, consistent with their derivation by cytoplasmic invagination into the nucleus. Capsids located within the nucleus outside the tegusomes were all naked, while those located in the cytoplasm were uniformly tegumented. In contrast, capsids present inside the tegusomes contains teguments of variable thicknesses. In addition, nucleocapsids were documented in the process of budding into the tegusomes. We thus suggest that the tegusomes represent a cellular site in which HHV-6 virions acquire their tegument.

Cell Nucleus↗

Does lead acetate intoxication damage acinar cell nuclei in the rat pancreas? ultrastructural observations.

The aim of the paper is to make an ultrastructural analysis of the nuclei of the pancreatic acinar cells in the rat in the course of lead acetate intoxication. The experiment used 84 Wistar rats, divided into 3 experimental groups, and a control group. The experimental rats were given aqueous solution of lead acetate in a dose of 50 mg/dm3 in group I, 500 mg/dm3 in group II and 1000 mg/dm3 in group III. The control rats were given tap water. The animals were killed 2,4 and 6 weeks after the experiment. The pancreatic tissue was collected for ultrastructural analysis and lead level was determined in the blood and in dry pancreatic mass in an atomic absorption spectrometer. After 6 weeks of lead acetate administration the levels increased 5 to 10-fold compared with the control group. It was ultrastructurally demonstrated that a low dose of lead caused chromatin margination, extension of perinuclear space and folding of acinar cell nucleus contours. Chronic administration of high lead doses resulted in the formation of pseudoinclusions and intranuclear real inclusions of the lead-protein complex. The alterations provided evidence of the toxic effect of lead upon the acinar cells nuclei in the pancreas.

Animals↗

The lung in tropical eosinophilia compared to that in pulmonary hypertension. Fine structural basis of respiratory disability.

Light and electronmicroscopic changes in lung biopsies were studied in six patients with tropical pulmonary eosinophilia, aged 20 to 37 years, of varying duration, and with severe haematologic (blood eosinophil count of 3,600 to 18,200 per mm3), and respiratory changes. On light microscopy the main pathologic reaction consisted of large mononuclear cells and eosinophils in and around the alveoli and blood vessels, and proliferated reticulin. Fine structural changes probably being described for the first time, included the presence of many alveolar macrophages characterised by abundant cytoplasm, irregular or stunted microvilli, increased phagolysosomes with ingested debris, and depletion of other organelles. Eosinophils bearing typical old and young granules, were encountered in and around the alveoli and blood vessels in all case, and collagenosis around alveolar cells in a few. Subacute pneumonitis producing compression and disorganisation of alveoli and blood vessels, and lack of normal apposition of air and blood spaces, appear responsible for the respiratory disability. The detection of mycobacteria, cocci or chlamydia-like bodies in two specimens and of intranuclear virus-like particles in another, could either indicate secondary infection or have an immunogenic significance, in the absence of detection of filarial elements in any of the specimens. Lung biopsies from two additional patients (aged 13 & 32) who had mitral stenosis probably due to rheumatic heart disease, and secondary pulmonary hypertension, were studied as "control" specimens. Both at light and electronmicroscopy these specimens did not show any eosinophils or neutrophils, and fewer macrophages in the lung parenchyma. In contrast to tropical eosinophilia and, as expected, there was considerably more fibrosis of the lung parenchyma, especially in the alveolar subepithelial region and in the vessel walls. This, together with fibroblasts full of endoplasmic cisterns, noted particularly in the younger patient with shorter duration, probably represented an earlier change in this condition.

Adolescent↗

Intranuclear filamentous inclusion in human oedematous cerebellar Golgi cells.

The presence of intranuclear filamentous inclusions in cerebellar Golgi cells is reported in three patients with cerebellar tumours. Samples of cerebellar cortex were processed for conventional transmission electron microscopy. Cerebellar biopsies were performed according to the basic principles of Helsinki declaration. Intranuclear inclusions observed in oedematous Golgi cells, appeared as straight rodlets up to 3 microm in length and up to 0.4 microm in width, characterized by a periodic or crystalloid structure formed by dense bands, 9.2 nm thick separated by clear spaces, 5.4 nm in width. These structures are considered abnormal protein aggregates apparently induced by excitotoxicity, oxidative stress and impaired energy metabolism.

Cerebellar Neoplasms↗

[Ultrastructure of B-cell tumors of the pancreas (insulinomas - insular carcinoid tumors)].

The subcellular organization of 6 B-cell tumours of the human pancreas was studied. The tumour parenchyma consisted of processed light, dark, and moderately electron dense cells containing insulin granules. The presence of villi in the cytoplasm of tumour cells and intranuclear fibrills was demonstrated. The participation of tumour cells in formation of amyloid-like thin-fiber substance filling the intercellular and perivascular spaces was established. The similarity between endothelial cells of tumour vessels and parenchymatous cells was shown. A hypothesis on neuroectodermal origin of the endocrine tissue of the pancreas is supported.

APUD Cells↗

Ca(2+)-independent isoforms of protein kinase C differentially translocate in smooth muscle.

It is generally assumed that smooth muscle contraction is dependent on changes in intracellular Ca2+ concentration ([Ca2+]i); however, we have previously reported that alpha-agonist-induced contraction of aorta smooth muscle cells can occur in the absence of changes in [Ca2+]i [Collins, E. M., M. P. Walsh, and K. G. Morgan. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H754-H762, 1992]. The mechanism of this [Ca2+]i-independent contraction is controversial. We have now identified the Ca(2+)-independent protein kinase C (PKC) isoforms epsilon and zeta in ferret aorta and have used digital imaging microscopy to determine their subcellular distribution. At rest, epsilon-PKC is diffusely distributed in the cytosol, whereas zeta-PKC is concentrated in the perinuclear region; both isoforms are excluded from the nuclear space. Agonist stimulation causes a [Ca2+]i-independent translocation of epsilon-PKC to the surface membrane and of zeta-PKC to the intranuclear compartment. In comparison, ferret portal vein cells, which display a totally Ca(2+)-dependent agonist contraction, are lacking in epsilon-PKC but display perinuclear zeta-PKC, which translocates intranuclearly on activation. Thus the Ca(2+)-independent vascular contraction appears to be associated with plasmalemmal translocation of epsilon-PKC; in contrast, the intranuclear translocation of zeta-PKC may function in control of gene expression.

Animals↗

[Intranuclear and cytoplasmic annulate lamellae in the polyploid giant cells of the trophoblast].

Intranuclear and cytoplasmic annulate lamellae in polyploid giant cells of the trophoblast have been studied in rat placenta on days 12--17 of development. The annulate lamellae are present in the cytoplasm within a limited time, being visible on day 12 only. These are arranged in bundles near the nucleus to be moving then to the cytoplasm. The end parts of annulate lamellae are broadened to make cisterns of rough endoplasmic reticulum. Unlike the cytoplasmic annulate lamellae, those found within the nucleus are seen in part of the nuclei investigated throughout the whole period examined to look as single structures (not gathered in bundles), they can be branching, separating closed spaces within the nucleus (making local swellings in the loci of branching; the latter having electron dense or transparent vesicles). Association with nuclear chromatin in some regions is a peculiar feature of the intranuclear annulate lamellae. This association is especially obvious at endoprophase in the cycle ofthe polytene nucleus during the somatic conjugation--chromonemes unite in a bundle and condense. Ultrastructural changes of the annulate lamellae is noted throughout the polytene nucleus cycle and during the cell differentiation. It is supposed that in the case of temporary labile chromosome polyteny in the nuclear cycle, which is characteristic of mammalian trophoblasts, annulate lamellae can well compare, in their function, with the synaptonemal complex--these prevent from too tight associations of homologues in the course of somatic conjugation of chromosomes.

Animals↗

Pleomorphic hyalinizing angiectatic tumor of soft parts.

A case of recently described pleomorphic hyalinizing angiectatic tumor (PHAT) of soft parts is reported. The subcutaneous solid tumor arising in the axilla of a 58-year-old man was histologically characterized by sheets of mitotically inactive oval and pleomorphic cells, intranuclear cytoplasmic inclusions, and clusters of ectatic vessels with perivascular hyalinization. Mono- and multinucleated giant cells were also present. A hemangiopericytoma-like pattern of vascularity, pseudovascular spaces, stromal collagen with degenerative changes, and immunoreactivity for CD34 were observed. Since these features were very similar to those of solitary fibrous tumors of various sites and newly categorized giant cell angiofibroma, it is considered that PHAT, solitary fibrous tumor, and giant cell angiofibroma may be in the same family of tumor. The tumor was diploid with a low S-phase fraction. The patient was well with no evidence of disease for 23 months.

Antigens, CD34↗

Adenovirus tubulointerstitial nephritis presenting as a renal allograft space occupying lesion.

This report describes a case of adenovirus infection in a renal allograft 36 days after transplantation that presented with transient macroscopic hematuria, prominent systemic features and acute renal dysfunction. The patient had persistent high fevers despite broad antibiotic cover. A CT scan demonstrated a new discrete space occupying lesion in the allograft, which was devoid of blood flow on Doppler sonography. A targeted renal biopsy showed florid and focal necrotizing interstitial nephritis with intranuclear tubular viral inclusions. Treatment with ganciclovir and reduction in immunosuppression resulted in a rapid improvement. Immunohistochemistry and electron microscopy confirmed adenovirus infection. This case demonstrates an uncommon presentation of necrotizing adenoviral nephropathy, which should be considered in cases of renal allograft mass lesions.

Adenoviridae↗

A model of chromosome aberration induction: applications to space research.

A mechanistic model and Monte Carlo code simulating chromosome aberration induction in human lymphocytes is presented. The model is based on the assumption that aberrations arise from clustered DNA lesions and that only the free ends of clustered lesions created in neighboring chromosome territories or in the same territory can join and produce exchanges. The lesions are distributed in the cell nucleus according to the radiation track structure. Interphase chromosome territories are modeled as compact intranuclear regions with volumes proportional to the chromosome DNA contents. Both Giemsa staining and FISH painting can be simulated, and background aberrations can be taken into account. The good agreement with in vitro data provides validation of the model in terms of both the assumptions adopted and the simulation techniques. As an application in the field of space research, the model predictions were compared with aberration yields measured among crew members of long-term missions on board Mir and ISS, assuming an average radiation quality factor of 2.4. The agreement obtained also validated the model for in vivo exposure scenarios and suggested possible applications to the prediction of other relevant aberrations, typically translocations.

Chromosome Aberrations↗

RNA metabolism in nuclei: adenovirus and heat shock alter intranuclear RNA compartmentalization.

Nuclear RNA compartmentalization has received little attention as an area where regulation of gene expression could occur. RNA transcription and processing occur in association with the nuclear matrix, a salt-insoluble proteinaceous network that fills the nuclear space and is contiguous with the peripheral lamina and pore complexes. Described here are experiments that determine the fate of nuclear RNA after it has completed these matrix-associated maturation steps. Continuous label experiments indicate that after nuclear RNA is processed it changes its state of attachment in the nucleus so that it is now removed from the nucleus in the high salt extraction step of matrix isolation. It is this salt-extractable RNA that will be transported to the cytoplasm. Late in adenovirus infection and following heat shock, when transport of cellular RNA is decreased, cellular transcripts do not make the transition from the matrix-associated to the salt-extractable nuclear pool. The implication of these data for the regulation of gene expression is discussed.

Adenoviruses, Human↗