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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 52 (1974), S. 559-567 
    ISSN: 1432-1440
    Keywords: Progressive myoclonus epilepsy (Lafora's disease) ; Type I (Unverricht, Lundborg) ; Type II ; Liver findings ; Clinical aspects ; Histology ; Ultrastructure ; Histochemistry ; Biochemistry ; Glycogenosis type IV ; Progressive Myoklonusepilepsie (Laforasche Erkrankung) ; Typ I (Unverricht, Lundborg) ; Typ II ; Leberbefunde ; Klinik ; Histologie ; Ultrastruktur ; Histochemie ; Biochemie ; Glykogenose Typ IV
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Dem klinischen Bild der progressiven Myoklonusepilepsie (Lafora's disease) liegt eine kongenitale Stoffwechselanomalie mit Ablagerung pathologischer Stoffwechselprodukte vorwiegend im Zentralnervensystem zugrunde. Der häufigere Typ I (Typ Unverricht, Typ Lundborg) zeigt eine regelmäßige Mitbeteiligung von Leber und Myokard sowie teilweise der Muskulatur, der seltenere Typ II ist mit seiner Speicherung nur auf das Zentralnervensystem beschränkt. Die Kenntnis der charakteristischen Leberbefunde kann einmal eine Hilfe sein für die klinische Unterscheidung von Typ I und Typ II, unspezifisch degenerativen Formen der Myoklonusepilepsie sowie gegenüber der myoklonischen Variante der amaurotischen Idiotie. Als eine weitere Möglichkeit könnte das bisher unbekannte Speicherprodukt und der auslösende spezifische Enzymdefekt auf diesem Wege identifiziert werden. Lichtmikroskopisch zeigen die Leberzellen — vorwiegend der Läppchenperipherie — und gelegentlich auch die Kupfferschen Sternzellen eine PAS-positive homogene Speichersubstanz, die in Übereinstimmung mit den Befunden am Zentralnervensystem und am Myocard elektronenoptisch aus granulärem und filamentärem Material aufgebaut ist. Die Deutung der einzelnen Untersucher hinsichtlich der histochemischen und biochemischen Ergebnisse variiert: die Natur des Ablagerungsproduktes wird als Mucopolysaccharid aber auch als Polyglucosan angesprochen. Übereinstimmend sieht man aber die Hauptstörung im Bereich des Kohlenhydratstoffwechsels. Die hier demonstrierten bemerkenswerten licht- und elektronenmikroskopischen Übereinstimmungen mit der Glykogenose Typ IV lassen nach unserer Auffassung nahe Beziehungen zur Gruppe der Glykogenosen annehmen. Als Thesaurismose ist die Laforasche Erkrankung eine potentielle Vorstufe der Cirrhose. Es entwickelt sich eine mehr oder minder ausgeprägte Mesenchymbeteiligung im Sinne einer chronischen Hepatitis. Eine komplette Cirrhose ist jedoch selbst bei den Spätfällen nicht nachzuweisen. Eine Hepatomegalie als Folge der Speicherung fehlt. Spezifische Leberproben fallen negativ aus. Das klinische Bild wird nicht von Seiten der Leber, sondern ausschließlich von der progredienten neurologisch-psychiatrischen Symptomatik der Myoklonusepilepsie geprägt.
    Notes: Summary The cause of clinical manifestations of progressive myoclonus epilepsy (Lafora's disease) is an inborn error of metabolism characterised by deposition of pathologic metabolic products in the central nervous system. In the most common type I (Type Unverricht, Type Lundborg) these deposits are regularly located in liver and myocard, and in some cases also in sceletal muscle. In the less common type II they are found only in the central nervous system. The characteristic liver findings might help to distinguish type I, type II, unspecific degenerative forms of myoclonic epilepsy and the myoclonic form of amaurotic idiocy. They also might be valuable in identification of yet unknown specific enzyme defect leading to tissue deposits. Our light microscopy observations demonstrate deposits of a PAS-positive homogene substance in liver cells—especially in the periphery of lobule— and sometimes in Kupffer cells. By electron microscopy this substance is identified as granular and filamentary material. This corresponds to our findings in the central nervous system and myocard. The interpretation of existing histochemical and biochemical studies did not yet solve the question, if the mentioned deposits are mucopolysaccharides or polyglucosanes, however, it is recognized that the main disorder is an error in carbohydrate metabolism. The notable similarity of our light- and electronmicroscopic observations to results obtained in glycogenosis type IV suggest that Lafora's disease might be another form of glycogenosis. As a thesaurismosis Lafora's disease can predispose to cirrhosis. The activation of mesenchyme, less or more pronounced, corresponds to chronic hepatitis. And even in the late forms a complete cirrhosis is not found. This thesaurismosis does not lead to hepatomegaly. Specific liver function tests are negative. The clinical course is characterised not by liver symptoms but by the neurologic and psychiatric symptoms of progressive myoclonic epilepsy.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 30 (1974), S. 345-354 
    ISSN: 1432-0533
    Keywords: Fabry's Disease ; Autopsy ; Histochemistry ; Biochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pathological and biochemical studies were performed on a patient with Fabry's disease. Abnormal deposits in the nervous system were restricted mainly to neurons of the autonomic nervous system. Affected neurons were found in the supraoptic and paraventricular nuclei, the midline nucleus, substriatal grey, nucleus amygdalae, presubiculum of hippocampus, fifth and sixth cortical layers of the parahippocampus and inferior temporal gyrus, dorsal motor nucleus of the vagus, superior and inferior salivatory nuclei, Edinger-Westphal nucleus, reticular formation of the pons and medulla oblongata, trigeminal ganglia, non-pigmented cells of the substantia nigra, intermediolateral column, spinal dorsal root ganglia, sympathetic ganglia and the submucous and myenteric plexuses. Abnormal deposits were found also in the periventricular glial cells, perineurium, the endothelial and smooth muscle cells of blood vessels throughout the body, the heart, kidneys and reticuloendothelial cells of many organs. The histogram of the sural nerve showed a decrease in the smaller myelinated and unmyelinated fibers. The abnormal deposits were glycolipids, CTH and CDH. Although there were two distinct staining characteristics of the deposited material with Luxol fast blue and PAS in paraffin section, these differently stained deposits could not be differentiated by histochemical and biochemical studies.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 27 (1974), S. 225-232 
    ISSN: 1432-0533
    Keywords: GM2 Gangliosidosis ; Juvenile Type ; Biochemistry ; Hexosaminidase A ; Altered Substrate Specifity ; Galactosaminidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The N-acetyl-β-d-hexosaminidases A and B were extracted from the liver tissue of a patient who died from juvenile GM2-gangliosidosis at the age of $$14{1 \mathord{\left/ {\vphantom {1 2}} \right. \kern-\nulldelimiterspace} 2}$$ years. The enzymes were separated from each other and studied in comparison to enzyme preparations from normal tissue. The kinetic parameters studied (pH profiles, Michaelis constants, heat lability) and the substrate specificity of the B-enzyme appeared normal. The activity of the A-enzyme against two artificial substrates was lowered in the pathological tissue to 53% and 41% of the control and to 27% of the control against the storage compound trihexosylceramide (ceramide-glucose-galactose-N-acetylgalactosamine). Furthermore, using the main storage compound ganglioside GM2 (ceramide-glucose-galactose-[N-acetylneuraminic acid]-N-acetylgalactosamine) as substrate, no N-acetyl-β-d-galactosaminidase activity was found in the extracts from pathological liver tissue.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 32 (1974), S. 115-130 
    ISSN: 1432-0738
    Keywords: Enzyme Induction ; Lindane ; Functional Tests ; Biochemistry ; Morphology ; Enzyminduktion ; Lindan ; Funktionelle Tests ; Biochemie ; Morphologie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach kurzzeitiger oraler Lindanapplikation (5 mg/kg, 20 mg/kg) wurden an männlichen Ratten verschiedene funktionelle, biochemische, histochemische und elektronenmikroskopische Untersuchungen angestellt. Dabei wurde keine Beeinflussung der Motilität und Exploration (open field-Test), der Lebergewichte und der histochemisch dargestellten Enzyme durch die Lindanmedikation gefunden. Die Schlafzeit, gemessen nach Pentobarbital i.p., war dosisund zeitabhängig reduziert. Der Leberglykogengehalt von behandelten und Kontrolltieren unterschied sich nicht, wenn die Tiere Futter ad libitum aufnehmen konnten. Nach 24 Std Futterentzug wurde bei den behandelten Tieren eine Tendenz zur Glykogenverminderung in der Leber festgestellt. Die Ascorbinsäureausscheidung im Urin war um ein Vielfaches erhöht, während das Blutserum eine Verdoppelung der Ascorbinsäurekonzentration aufwies (als Transporteffekt gedeutet). Elektronenmikroskopisch fand sich eine deutliche Vermehrung des glatten, endoplasmatischen Reticulum, besonders in Hepatocyten der Intermediärzone. Die gefundene Zunahme freier Ribosomen wird mit der verstärkten Bildung von mikrosomalem Protein in Verbindung gebracht. Die auch elektronenoptisch dargestellte Glykogenverminderung einzelner Zellen läßt sich als Folge des unter der Enzyminduktion veränderten Metabolismus (erhöhte Glucuronsäurebildung, verstärkte Ascorbinsäuresynthese) erklären. Insgesamt konnte mit der gegebenen Versuchsanstellung kein Hinweis auf hepatotoxische Wirkungen der Prüfsubstanz gefunden werden, so daß sich die funktionellen und morphologischen Äquivalente der Enzyminduktion als adaptative Veränderungen interpretieren lassen.
    Notes: Abstract Following short-term oral administration of Lindane (5 mg/kg, 20 mg/ kg) to male rats, various functional, biochemical, histochemical and electronmicroscope investigations were performed. No effects of the Lindane medication were found in movement and exploration (open-field test), liver weight, and the histochemically presented enzymes. A dose-dependent and time-dependent reduction in the duration of sleep was measured after i.p. pentobarbital. There were no differences in the liver glycogen levels of treated and control animals when food was available to the animals ad libitum. After food had been withdrawn for 24 h, a tendency to reduced liver glycogen was observed in the treated animals. The excretion of ascorbic acid in the urine was several times higher than normal, while the ascorbic acid concentration in blood serum was doubled (attributed to transport effect). The electron microscope revealed a distinct increase in the smooth endoplasmic reticulum, particularly in hepatocytes of the intermediary zone. The observed increase in free ribosomes was thought to be connected with the intensified formation of microsomal protein. The reduced glycogen of individual cells, also observed with the electron microscope, was explained as a result of the change in metabolism caused by enzyme induction (increase in formation of glucuronic acid, increased ascorbic acid synthesis). In all, no hepatotoxic effects of the test substance were found with the given experimental procedure, so the functional and morphological equivalents of enzyme induction can be interpreted as adaptive changes.
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  • 5
    ISSN: 1432-1106
    Keywords: Hypothalamo-neurohypophyseal system ; Dehydration ; Acid phosphatases ; Biochemistry ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activities of acid orthophosphoric-monoester-phosphohydrolases in the supra-opticus nucleus and the neurohypophysis of the rat were measured at pH 4.1 and 5.3 by biochemical assay and by histospectrophotometric method after a thirsting period of 1–12 days. For the neurohypophysis the biochemical and histophotometrical results are convergent. These enzymatic activities increase during the entire experimental period but if the biochemical results are expressed for 100 μg of proteins the elevation is only significant at pH 4.1. For the supra-optic nucleus, changes in enzymatic activities are different by histophotometric and biochemical methods. It is assumed that in the rat hypothalamo-neurohypophyseal system the acid phosphatases are distributed between two separate pools: (1) one strongly bound to cytoplasmic membrane structures, particulary abundant in the perikarya of the supra-optic nucleus, and (2) another pool of “free” or easily discharged enzyme, the major component in the neurohypophysis; our biochemical assay measures only this “free pool”. The role of these pools in the synthesis and release of vasopressin is presumably different.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 30 (1974), S. 91-107 
    ISSN: 1432-0533
    Keywords: Pierre Robin Syndrome ; Neuropathology ; Biochemistry ; Undernutrition ; Cerebral Hypoxia ; Cerebral Development ; Mental Retardation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical, light and electron-microscopic, and biochemical observations are presented in an 11 years old boy with Pierre Robin Syndrome; micrognathia, cleft palate and glossoptosis. Respiratory distress and feeding difficulties were early and serious complications of the glossoptosis. “Cachexia”, a striking physical underdevelopment, profound psychomotor retardation and epilepsy constituted the prominent clinical features. The neuropathology of the syndrome was characterized by the following: 1. Arrest in cerebral growth and maturation; 2. Mild diffuse and laminar cortical neuronal losses and astrocytic fibrosis; and 3. Minor histogenetic anomaly in the cerebellar cortex. The arrest in cerebral development was reflected grossly by microencephaly and, histologically by “immaturity” of numerous cortical neurons, poverty of intracortical fibrillary plexuses, poor establishment of cytoarchitectonic characteristics and hypoplasia of hemispheric white matter. At subcellular level, there was diminution of cytoplasmic organelles, particularly the rough endoplasmic reticulum. A marked deficiency in myelin lipids and severe diminution of total ganglioside concentration in the cerebral cortex were the major biochemical findings. In the pathogenesis of cerebral alterations congenital factors and the complications of “glossoptosis” were considered. It was suggested that the early undernutrition played an important role in the impediment of cerebral growth and maturation. The cerebral hypoxic insults further curtailed the development of already compromised neurons and depressed their functional activities, particularly in the more susceptible cerebral cortex. It was proposed that the arrested brain development provided a substantial structural basis for the psychomotor retardation.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 26 (1973), S. 93-106 
    ISSN: 1432-0533
    Keywords: Leucodystrophy, Metachromatic, Juvenile ; Sulfatide Accumulation ; Biochemistry ; Myelination ; Metabolic Derangement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical history, histopathological, ultrastructural and biochemical observations are presented in a juvenile MLD with onset at 8 years and death at 20 years. The findings are compared with related ones in different age groups, and current views on sulfatide metabolism and enzymatic pathogenesis in MLD are briefly entertained. It is postulated that the relatively well established morphological and chemical stability of the nervous tissue at the time of appearance of the metabolic derangement was an important factor in the pathomechanism of the disease process in this particular variant.
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  • 8
    ISSN: 1432-0878
    Keywords: Neurosecretory tract (eel) ; Transport of hormones ; Arginine-vasotocin ; Ichthyotocin ; Biochemistry ; light microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Résumé Une étude pharmacologique et histologique des transformations enregistrées le long du tractus neurosécrétoire est réalisée chez l'anguille européenne après hypophysectomie totale. Les animaux, sacrifiés entre 8 jours et 150 jours après hypophysectomie, sont d'abord examinés sur le plan quantitatif en suivant le devenir de l'arginine-vasotocine et de l'istotocine dans les parties antérieure (noyau préoptique) et caudale du tractus neurosécrétoire. L'étude est ensuite effectuée sur un plan qualitatif, en suivant, pour les mêmes territoires et les mêmes périodes de temps, les transformations notées pour le neurosécrétat. Les résultats obtenus au moyen de ces deux techniques d'investigation sont comparés. 1. Sur le plan quantitatif, l'expérience montre que l'évolution de l'arginine-vasotocine est différente de celle de l'isotocine, et qu'une distinction peut être faite entre les parties antérieure et caudale du tractus neurosécrétoire. En règle générale, et particuhèrement pour le premier peptide, lorsqu'il y a chute de concentration au niveau préoptique il y a augmentation de concentration dans la partie caudale, ce qui permet de traduire le cheminement des hormones. 2. L'expérience montre également que les hormones sont toujours présentes, mais subissent des chutes de concentration très importantes. 3. Le contrôle histologique confirme les résultats précédents, et montre des variations importantes dans la quantité et la colorabilité du neurosécrétat.
    Notes: Summary A pharmacological and histological study of the transformations of the neurosecretory material observed along the neurosecretory tract of the hypophysectomized eel has been performed. The animals, sacrificed within a period of 8 to 150 days after hypophysectomy, have been first examined on a quantitative level by registrating the concentration of arginine-vasotocin and ichthyotocin in the anterior (preoptic nucleus) and caudal parts of the neurosecretory tract. The study was then transferred to a qualitative level for the same regions and post-operative times, to follow up the transformations of the neurosecretory material. The results obtained with these two approaches of investigation are compared. 1. On the quantitative level, the experiments showed that the arginine-vasotocin behaves differently if compared with ichthyotocin, and that a difference exists between the anterior and caudal parts of the neurosecretory tract. In general, a decrease of concentration in the preoptic nucleus is followed by an increase of concentration in the caudal part. This is particularly obvious in the case of the arginine-vasotocin. This result speaks in favour of the transport of hormones along the neurosecretory tract. 2. The experiment showed also that the hormones are always present, but show an important decrease in concentration. 3. The histological control confirmed the pharmacological results, showing great variations of the quantity and stainability of the neurosecretory material.
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  • 9
    ISSN: 1432-0878
    Keywords: Intestine, Lampetra fluviatilis ; Serotonin-, dopamine-, noradrenaline-containing neurons ; Identification by histochemistry ; Electron microscopy ; Biochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Monoamine-containing neurons in the gut of Lampetra fluviatilis are characterized by histochemical, electron microscopical and biochemical methods. Strongly yellow fluorescent, probably serotonin-containing intrinsic neurons are found along the entire length of the intestine. Their processes aggregate to form large bundles of mainly non-terminal axons, constituting a subepithelial fibre plexus. This subepithelial, ganglion cell comprising plexus is connected to a wide-meshed subserosal plexus which has ganglion cells of different size and few varicose, single axons. Intermingled with both plexus there occur — in the anterior and middle but not in the preanal portion of the lamprey intestine — scattered green fluorescent intrinsic perikarya, emanating faintly green fluorescent, poorly varicosed axons. The formaldehyde-induced neuronal fluorophores conform to serotonin (yellow fluorescent compound), noradrenaline, and dopamine (green fluorescent substance), as revealed in microspectrofluorimetric recordings. The electron microscopical analysis of the yellow fluorescent intrinsic neurons in the terminal hindgut shows nerve cell pericarya and axons equipped with a typical population of occasional small granular and many large granular vesicles (750–1600 Å). The number and opacity of cores of the small and the osmiophilia of the cores of the large granular vesicles are significantly increased following short-term treatment with 5,6-dihydroxytryptamine. Long-term treatment with 5,6- or 5,7-dihydroxytryptamine provokes severe signs of ultrastructure impairment and eventual degeneration in the supposed serotonin-containing axons, besides indications of piling-up of organelles in the non-terminal axons due to arrest of axonal transport. Chromatography of acid extracts from the lamprey intestine, gills and kidney reveals the presence of serotonin (besides another unidentified indoleamine) and dopamine and noradrenaline in the gut, but only dopamine in the brain. The detection of serotonin, noradrenaline and dopamine in the lamprey gut is confirmed by chemical determinations. The occurrence of intrinsic serotonin-, noradrenaline- and dopamine-containing neurons in the gut of Lampetra fluviatilis deviates from the established pattern of innervation of the vertebrate intestine and is considered to be a remnant of an autonomic innervation principle common in invertebrates.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 114 (1971), S. 365-389 
    ISSN: 1432-0878
    Keywords: Forestomach epithelium ; Goat ; ATPases ; Cytochemistry ; Ultrastructure ; Biochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Am Epithel der drei Vormägen der Ziege wurden licht- und elektronenmikroskopische Untersuchungen über den Nachweis der Mg++-, (Mg++-Na+-K+)- und der Ca++-aktivierbaren ATPasen durchgeführt. Bereits an lichtmikroskopischen Präparaten wurde festgestellt, daß sich deutliche Unterschiede in der Enzymaktivität der Mg++- und Ca++ stimulierbaren ATPasen sowohl für die einzelnen Epithelschichten als auch für die verschiedenen Bereiche der Vormägen nachweisen lassen; die tiefen Epithellagen reagieren stets stärker als die oberflächlichen. Ferner ist die in hohem Maße von der Inkubationszeit abhängige Reaktionsstärke im Epithel des Blättermagens größer als in der Lamina epithelialis des Netzmagens und vor allem in jener des Pansens. Bei dem elektronenmikroskopisch geführten Nachweis der ATPasen zeigt sich, daß die Reaktionsprodukte an der Außenseite der Zellmembranen liegen. Frei von Niederschlägen sind alle Zellmembranabschnitte, die sich an der Bildung der Desmosomen und Halbdesmosomen beteiligen sowie die basalen Abschnitte der Basalzellen. Im Hinblick auf die Verteilung und feinstrukturelle Lokalisation konnten keine Unterschiede zwischen den Mg++-, Ca++- und (Mg++-Na+-K+)-aktivierbaren ATPasen beobachtet werden. In Anlehnung an die Methode nach Coleman u.a. (1967) wurden Zellmembranen von Pansenepithelzellen isoliert und an diesen biochemische Enzymbestimmungen durchgeführt. Die Ausbeute der gewonnenen Zellmembranen betrug, gemessen anhand der 5′-Nukleotidase, dem Leitenzym für Plasmamembranen, gegenüber dem eingesetzten Gesamthomogenat 0,3%. Die mit diesem Verfahren durchgeführten biochemischen Enzymbestimmungen erbrachten den Nachweis, daß in den Plasmamembranen der Pansenepithelzellen neben der Mg++- und Ca++-aktivierbaren auch eine (Na+-K+)-abhängige Transport-ATPase vorkommt.
    Notes: Summary Light- and electron microscopical studies were carried out to demonstrate ATPases activated by Mg++, by (Mg++-Na+-K+), and by Ca++. Histological sections showed clear differences of the activity of Mg++- and Ca++-stimulated ATPases in the light microscope in different layers of the epithelium as well as in different areas of the forestomach. The deeper layers reacted more intensely than the superficial ones. The intensity of the reaction (which depends on incubation time) in the omasal epithelium was stronger than in the lamina epithelialis of the reticulum and much stronger than in the lamina epithelialis of the rumen. In the electron microscope, the reaction products of the ATPase appeared on the outer surface of cell membranes (plasmalemmata). No deposits of the reaction products were observed on those areas of the cell membranes, which are involved in the formation of desmosomes and semidesmosomes. The basal parts of the basal cells were also free from reaction products. As for the distribution and ultrastructural localisation of the deposits, no differences were observed among the ATPase stimulated by Mg++, (Mg++-Na+-K+), and Ca++. Using the technique of Coleman et al. (1967), the cell membranes of ruminal epithelium were isolated. Biochemical assays of the enzymes were carried out. The quantity of cell membranes obtained was 0.3% of the whole homogenate, when compared with 5′-nucleotidase, which is the typical enzyme of plasmalemmata. The biochemical enzyme assays showed that, besides Mg++- and Ca++-dependent ATPases, a (Na+-K+)-dependent transport ATPase exists in the cell membranes of ruminal epithelial cells.
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