Paracrystalline Inclusions Research Articles

Ultrastructure of Paracriny/Steroidogenesis in Principal Cells of the Marmoset Epididymis

The ultrastructural features of the principal cell in the epididymal epithelium of the marmosets are distinguished by an intercellular exchange of substances contained within cytoplasmic vesicles and the presence of paracrystalline bodies. The possibility of the exchange of substances constituting paracriny and the paracrystalline inclusion having a role in steroidogenic activity is discussed.

Neuroepithelial Endocrine Cells in the Lung of the Lungfish Protopterus aethiopicus

The occurrence and distribution of neuroepithelial endocrine (NEE) cells was demonstrated electron- and fluorescence-microscopically in the lungfish Protopterus aethiopicus. They were only found to occur solitarily in the basal part of the cilio-mucous epithelium which is restricted to the pneumatic duct and adjacent parts of the common anterior chamber. The NEE cells show a yellow, formaldehyde-induced fluorescence. Electron-microscopically, all the NEE cells are characterized by membrane-bound electron-dense secretory granules with varying diameters, ranging from 75 to 150 nm. These granules are distributed throughout the cytoplasm with a higher concentration in the basal region. The NEE cells were regularly found to contain paracrystalline inclusions with a tubule-like substructural arrangement. A small part of the NEE cells appeared to reach the luminal surface by means of a long slender process bearing specialized beaded microvilli on its apical pole. Intraepithelial nerve fibres, with the ultrastructural characteristics of afferent fibres, were found running parallel to the airway surface. Nerve profiles, largely resembling the latter, can be seen in the proximity of the basolateral plasma membrane of the NEE cells. In addition, nerve terminals containing an aggregation of small clear vesicles are in close contact with the NEE cells. In conclusion, it appears that, as has so far been assumed in higher vertebrates, the NEE cells in the lung of Protopterus may perceive changes in the airway gases whereupon they could respond by releasing a chemical modulator, influencing contacting afferent nerve terminals or nearby smooth muscle bundles. Furthermore, intraepithelial nerve fibres or NEE cells might be stretch-sensitive.

The fate of intramitochondrial paracrystalline inclusion bodies in germ line cells of water frogs (Amphibia, Anura)

Numerous intramitochondrial paracrystalline inclusion bodies (ICIB) were observed in the germinal plasm of a mid-blastula, and in primordial germ cells (PGCs) after their migration to the germinal ridges, in Rana ridibunda, R. lessonae and R. esculenta. In oogonia the number of ICIB decreases rapidly. Single ICIB are observed in the germ cells up to the leptotene stage; they have never been observed in pachytene oocytes. In diplotene oocytes that have reached a diameter of about 100 microns ICIB are visible again, and their number increases concomitantly with oocyte growth.

Clinico - pathological features of mitochondrial cytopathy - a study of 8 cases in hong kong

Eight patients with mitochondrial cytopathy are discussed. This presentation documents the occurrence of the disease 1n Chinese as well as exemplifies many of the recognised syndromes. Two patients presented with myoclonus epilepsy associated with ragged red fibres (MERRF), one with mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS), one with external ophthalmoplegia, retinitis pigmentosa and congenital heart block (Kearns Sayre Syndrome) and four patients with less well-defined syndromes. The diagnosis 1s essentially a pathological one» established by muscle biopsy examination 1n an appropriate clinical setting. Ragged red fibres and intramitochondrial paracrystalline inclusions are found each case. The clinical heterogeneity of mitochondrial cytopathy 1n the presence of identical pathological changes in skeletal muscle 1s emphasized.

White matter ultrastructural pathology of experimental Creutzfeldt-Jakob disease in mice

Creutzfeldt-Jakob disease (CJD), previously regarded as a neurodegenerative disorder strictly of the gray matter, occasionally occurs as a panencephalopathic form which is characterized by severe white matter damage. An ultrastructural study of the white matter pathology in mice experimentally infected with the Fujisaki strain of CJD virus revealed: (1) vacuoles within myelin sheaths, formed by splitting either at the major dense or intraperiod lines, or within axons; (2) macrophages filled with numerous myelin figures, lipid droplets and paracrystalline inclusions; (3) astrocytes actively digesting myelin debris; (4) unusual wrapping of several axons by a common myelin sheath; (5) vesicular degeneration of myelin sheaths; (6) close contact between numerous coated pits and outer myelin lamellae; and (7) proliferation of inner mesaxons. Our data indicate that the damage to myelinated axons in the panencephalopathic type of CJD is accomplished primarily by active degradation of myelin by macrophages and astrocytes and by formation of intra-axonal and intra-myelin vacuoles. The myelin vacuolation is most consistent with that produced by leukolysins released from activated macrophages and astrocytes.

Membranous changes in primary malignant CNS lymphomas.

Ultrastructural studies of 17 primary malignant CNS lymphomas revealed 6 tumors with abnormal intracytoplasmic and/or intranuclear membranous structures, most frequently associated with the endoplasmic reticulum or perinuclear envelope. In most cases, tubuloreticular inclusions and paired cisternae were present. Less frequent were accumulation of microtubules, concentric lamellar bodies, and rod-like or paracrystalline intranuclear inclusions. The specificity and significance of these membranous structures remain questionable because of their frequent occurrence in a variety of normal and pathological conditions. Some of these changes may be considered as cellular reactions to viral infections, others may indicate cellular activity or degeneration.

Myoclonic epilepsy and ragged‐red fibers with cytochrome oxidase deficiency: Neuropathology, biochemistry, and molecular genetics

A 36-year-old man with myoclonic epilepsy and ragged-red fibers (MERRF) died after more than 18 years of follow-up study. He was 1 of 3 affected siblings and the offspring of an affected mother, suggesting maternal transmission. At autopsy, there was neuronal loss and gliosis in the dentate nucleus of the cerebellum and in the inferior olivary nucleus. Skeletal muscle showed ragged-red fibers, and paracrystalline inclusions in mitochondria by electron microscopy. Biochemical analysis showed a generalized partial defect of cytochrome c oxidase (COX) in mitochondria isolated from all tissues, including brain, heart, skeletal muscle, kidney, and liver. The Michaelis constant (Km) for cytochrome c was abnormally low, suggesting a defect of the mitochondrially encoded subunit II of COX. Immunological studies (enzyme-linked immunosorbent assay, dot-blot, Western blot, and immunohistochemistry) showed that the holoenzyme was decreased but subunit II was decreased more than the holocomplex or the nuclearly encoded subunit IV. However, Northern and Southern blots showed that the gene for subunit II, as well as the genes for subunits I, III, IV, and VIII, were of normal size and were normally transcribed. A point mutation or a small deletion of mitochondrial DNA, probably affecting the COX-II gene, may be responsible for the COX deficiency in this case of MERRF.

3,4,3',4'-Tetrachlorobiphenyl-Induced Effects in the Rat Liver. I. Serum and Hepatic Retinoid Reduction and Morphologic Changes

The distribution of 3,4,3',4'-tetrachlorobiphenyl (TCB), its effects on serum and hepatic retinoid, content and liver morphology were investigated in adult female WAG/Rij rats. Animals received a single intraperitoneal injection of either a corn oil vehicle, 15 or 200 mg TCB/kg body weight and were killed at 1, 3, 7, and 14 days after treatment. One rat of the high-dose group that had received 200 mg TCB/kg containing 1.85 mCi of 3H-TCB was sacrificed at each sampling time. There was a significant increase in liver weight when expressed as a percentage of body weight in the high-dose group at day 3 (122% of controls), day 7 (116% of controls), and day 14 (110% of controls). There was a rapid rise in the amount of 3H-TCB present in the liver that peaked at day 7 followed by a rapid decline in the amount of radiolabelled material by day 14. Greater than 90% of the radiolabelled material in the liver was parent compound. TCB treatment induced a significant decrease in serum retinol content in the high-dose group at day 3 (39% of controls) and day 7 (46% of controls) following exposure. There was a significant decrease in hepatic retinol content in the high-dose group at day 3 (34% of controls), day 7 (25% of controls), and day 14 (42% of controls) following exposure. TCB treatment induced a significant decrease in hepatic retinyl palmitate content in the high-dose group at day 7 (56% of controls) following exposure. Ultrastructural alterations in hepatocytes included the proliferation and vesiculation of endoplasmic reticulum, and mitochondrial enlargement with paracrystalline inclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4,3,4'-Tetrachlorobiphenyl-Induced Effects in the Rat Liver. II. Electron Microscopic Autoradiographic Localization of H-TCB

Recent results (3) indicate that 200 mg 3,4,3',4'-tetrachlorobiphenyl induces hepatomegaly accompanied by significant decreases in serum and hepatic retinoid content and hepatocyte morphologic alterations of proliferated and vesiculated endoplasmic reticulum and megamitochondria with paracrystalline inclusions. There was also an associated change in the number, size, and distribution of lipid droplets in hepatocytes and fat-storing cells. Electron microscopic autoradiographic techniques were utilized to determine the cellular and subcellular distribution of 3H-3,4,3',4'-tetrachlorobiphenyl (3H-TCB) in the adult rat liver and determine if there is any relationship between subcellular morphologic change and radiolabel localization. Adult female WAG/Rij rats received a single intraperitoneal injection of 200 mg TCB/kg containing 1.85 mCi of 3H-TCB and were sacrificed at 1, 3, 7, and 14 days following exposure. The vast majority of 3H-TCB-derived radioactivity was located in the hepatocyte at all time points examined, ranging from 79-86% of the total number of autoradiographic grains counted over the liver cells. Sequential order of radiolabel localization per liver cell type at 1, 3, and 7 days was hepatocyte much greater than Kupffer cell greater than fat-storing cell greater than endothelial cell. At day 14, the sequential order of radiolabel localization per liver cell type was hepatocyte much greater than fat-storing cell greater than Kupffer cell greater than endothelial cell, which indicates that there was some shift movement of label over time. The lipid droplet, mitochondria, and endoplasmic reticulum were the subcellular structures or organelles of hepatocytes having the highest number of 3H-TCB-derived grains at all time periods examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Paracrystalline inclusions in metaplastic ciliated cells of the human gastric mucosa

Unusual electron-dense paracrystalline inclusions were found in metaplastic ciliated cells in the stomachs of three Japanese male patients with gastric carcinoma. These patients had not been given antitumour drugs before surgery and ethrane (enflurane) was used as the anaesthetic. Ciliated cells in the gastric mucosa are found not infrequently in the pyloric glands in association with intestinal metaplasia in elderly Japanese patients. Paracrystalline inclusions were found only in the ciliated cells and never in any other types of gastric mucosal cell. These inclusions were located in the apical portion of the ciliated cells in intimate association with the basal bodies. They consisted of twisted strings about 27 nm wide with a regularly repeated spacing of about 30 nm. On highly magnified electron micrographs, granules about 4 nm in diameter were detected. These paracrystalline inclusions have never been reported previously, although their location in ciliated cells and their morphological characteristics suggest an intimate relationship with the ciliogenesis of metaplastic ciliated cells in the human stomach.

Mitochondrial abnormalities in extraocular muscles in myotonic dystrophy

This is the first description of ‘ragged red fibers’ in extraocular muscles of myotonic dystrophy. Muscle biopsies were obtained from the biceps brachii and superior rectus of a 53-year-old man who had suffered from chronic progressive myotonia and muscular weakness in limbs, blepharoptosis, external ophthalmoparesis, myotonic cataract, and foveal pigmentary dystrophy. The extraocular as well as skeletal muscle cells showed centrally placed multiple nuclei with type 1 fiber predominance and increased intermyofibrillary connective tissue. About 20% of extraocular muscle fibers were identified as ‘ragged red fibers’ with the modified Gomori trichrome stain, most of which showed reduced activity in the cytochrome c oxidase reaction. An increased number of enlarged mitochondria were clustered beneath the sarcolemma and between the myofibrils, some of which contained irregularly or circularly arranged cristae and paracrystalline inclusions. Biochemical assessments showed in both skeletal and extraocular muscle...

Ultrastructural analysis of leucocyte interaction with tumour targets in a teleost, Cyprinus carpio L

The first step in natural killer activity, target cell binding, was investigated ultrastructurally in order to identify presumptive cytotoxic cells. After incubation of unfractioned peripheral blood cells of the carp, Cyprinus carpio L. , with HeLa tumour cells as targets, regular conjugate forming was observed. Targets were surrounded by cells bearing features either of lymphocyte or monocyte/macrophage types. Cells with the usual lymphocytic characteristics contained acid phosphatase positive granules of various density and — after two hours of incubation — paracrystalline inclusions were observed. Cells with monocyte/macrophage morphology were characterized by abundant organelles, varying granules and occasional phagolysosomes. In both cell types development of the contact area was similar to those events known from mammalian cytotoxic cells: development of interdigitating microvilli and increase in the reoriented secretory apparatus (both more intense in the monocyte / macrophage cells than in the lymphocytes). The possibility of several cytotoxic cell types instead of one primitive cytotoxic precursor type proposed earlier in literature is discussed.

Muscle in Hallux Valgus

Muscle imbalance is cited widely as a major factor in the production of hallux valgus deformity. The authors, therefore, performed muscle biopsies in 57 patients (53 women and four men; average age, 45.3 years) to examine the histology and ultrastructure of the intrinsic muscles about the great toe. The biopsy study was correlated with gait analysis. In 53 biopsy specimens the muscles were found to be histologically abnormal, presenting myogenic and neurogenic alterations. Furthermore, ultrastructural examination showed enlarged mitochondria with paracrystalline inclusions in 31 of the 57 cases. Gait analysis showed an abnormal rollover pattern in 70% of the gait cycles examined in 19 symptomatic hallux valgus patients (18 women and one man), while in 19 asymptomatic volunteers (16 women and three men) 80% of the cycles examined were normal. The surface electromyographic (EMG) activity of the intrinsic muscles also was abnormal in the patient group when compared with the volunteer group; five different patterns of electrical activity were found. These findings may be interpreted as a result of chronic ischemia caused by the elevated pressure occurring within the foot during gait.

High molecular weight microtubule-associated proteins bind to actin lattices (Hirano bodies).

Hirano bodies are filamentous, paracrystalline inclusions that are found in dendrites and cell bodies of neurons in Alzheimer's and other neurodegenerative diseases. Actin appears to be a major component of these structures. We present evidence that tropomyosin and high molecular weight microtubule-associated proteins (MAPs) are also components of Hirano bodies. Although an association between actin and MAPs has been noted in vitro, interactions in vivo have not heretofore been demonstrated. Since microtubules are not present in Hirano bodies, and anti-tubulin and anti-neurofilament antibodies do not bind to Hirano bodies, the association between MAPs and these inclusions is likely a result of interactions between MAPs and actin, and not MAPs and microtubules or neurofilaments.

Ultrastructural Features of Ontogeny of Pollen inCapparis SpinosaL. VAR.Inermis

SUMMARYThe pollen ontogeny of Capparis spinosa L. var. inermis was studied under the light and electron microscopes. Paracrystalline inclusions are present in plastids of the microspore mother cells during meiosis. Microspore tetrads are isobilateral with moderately proliferating dictyosomes, poorly structured plastids and lipid bodies in the cytoplasm. In the late tetrad period, the nuclear envelope is apparently the site of protein synthesis and storage. Release and microspore development in the free period are normal. The mature pollen grain is bi-celled, spindle-shaped and tricolpate with smooth exine. Dictyosomes are numerous and preferentially clustered in the pore regions. Ergastoplasm cisternae are more common in the peripheral cytoplasm. The plastids do not contain starch which is also absent from the sporogenous cells, during microsporogenesis and in all stages of microspore development.

Hirano bodies contain tau protein

Hirano bodies are intraneuronal inclusions whose frequency increases with age and Alzheimer's disease. These paracrystalline inclusions have been shown previously using immunocytochemistry to share epitopes with actin, tropomyosin, α-actinin and vinculin. Hirano bodies have not previously been demonstrated to share components with neurofibrillary tangles, another intraneuronal inclusion characteristic of Alzheimer's disease. In this study, we show that Hirano bodies bind antibodies to the microtubule-associated protein tau, a component of Alzheimer neurofibrillary tangles.

Peripheral neuropathy in mitochondrial disease

Clinical, electrophysiological, histological and biochemical studies of two patients with mitochondrial disease revealed a moderately advanced axonal neuropathy with mitochondrial paracrystalline inclusions in Schwann cells, fibroblasts and muscle fibers. In addition there was a myopathy, and the activity of muscle cytochrome c oxidase was diminished by more than 50%. There were electrophysiological signs of myopathy, neuropathy and failure of excitation-contraction coupling in both patients. The partial enzyme deficiency raises some questions as to its pathogenetic role in these neuromyopathies.

Hepatic ultrastructural changes and liver dysfunction in amyotrophic lateral sclerosis.

Ultrastructural changes of hepatocytes were studied in liver biopsy specimens obtained from 21 patients with amyotrophic lateral sclerosis (ALS). In all specimens, one or more of the following abnormal findings were made: bizarre giant mitochondria; intramitochondrial paracrystalline inclusions; disorganization of the lamellar structure of rough endoplasmic reticulum; increased numbers of smooth endoplasmic reticulum; and/or parasinusoidal fibrosis. Above all, paracrystalline inclusions appeared to be a highly specific finding in ALS. In light of the above pathologic findings, we evaluated the liver function tests of 37 patients (including the above-mentioned 21 patients) with ALS, and found a high incidence of mild liver dysfunction. In spite of its subtleness, these ultrastructural changes of hepatocytes were consistently found in such patients, and offer further insight into the intrahepatic metabolic abnormalities in ALS.

The digital structural analysis of helical hirano bodies obtained by electron microscopy

A digital structural analysis method with the aid of a scanning densitometer was successfully applied to paracrystalline inclusion bodies which have been found in the brains of humans exhibiting senile dementia. Based on Fourier techniques involving noise removal and enhancement for structural analysis from a computer-generated diffractogram, it is proposed that the crystalline bodies from thin sections of the specimen constitute a stranded helix of 18.5 nm pitch. From the digital processed data obtained from the various different electron micrographs obtained by the use of a tilting device, a three-dimensional model and Fourier synthetic images representing the precise arrangement of the Hirano body stranded helix are derived and graphically demonstrated.

Peripheral neuropathy associated with mitochondrial myopathy

Twenty patients with mitochondrial myopathy were investigated for the presence of peripheral neuropathy. There were clinical features of a mild sensorimotor neuropathy in 5 patients (25%) and nerve conduction studies were abnormal in 10 patients (50%). Electrophysiological studies of the whole group showed significant impairment of motor and sensory conduction, compared with controls. Sural nerve biopsy and morphometric studies were performed on 4 patients with clinical neuropathy. There was a reduction in density of myelinated fibers and electron microscope features of axonal degeneration affecting myelinated and unmyelinated fibers. Abnormal mitochondria containing paracrystalline inclusions were seen in the Schwann cell cytoplasm of two nerves.