Günter Ule

Morphological feedback effect on neurons of the nucl. arcuatus (sive infundibularis) and nucl. subventricularis hypothalami due to gonadal atrophy

We have correlated the light-microscopic features in the un-myelinated hypothalamus with gonadal atrophy in 15 women of 30-111 years of age and in 7 men between 29 and 82 years. In the postmenstrual cases there is a distinct concordance of gonadal atrophy and the manifestation of nucleolar changes (augmentation, multiplication and vacuolization) in many nerve ceils of the arcuate and subventricular nuclei. In younger, still fertile women this nucleolar finding was seen only rarely and sporadically, was limited to the arcuate nucleus and was absent in the subventricular nucleus. We interpret this nucleolar finding as a feedback effect. In man, too, this coincidence is obvious with age and in gonadal atrophy, with fewer nucleolar changes in old age than are seen in women. This difference is probably caused by a more rapid drop of the estradiol than of the testosterone level.-The hypertrophy of the subventricular nucleus (Sheehan and Kovacs) was also observed in our postmenstrual cases.

Maligner Granularzelltumor des Großhirnmarkes

SummaryThis is a report of the second known case of a primary malignant granular-cell tumor of the cerebral hemispherical white matter. Two cell types may be distinguished apparently representing different developmental stages of otherwise identical tumor cells. Quantitative histochemical and biochemical studies have shown that tumor cells were containing markedly elevated levels of DNA and RNA. Only few ribosomes and polysomes could be detected, however, by electron microscopy. While cytophotometry disclosed only slightly elevated cytoplasmic proteins, there was a distinct increase in total protein concentration of tumor tissue per unit weight, as measured by conventional techniques. It is suggested that this increase is mainly attributable to structural proteins of cellular and subcellular elements of multiplicating malignant cells. A ratio of RNA to DNA in excess of 1 was found for white matter derived from the central tumor, while the ratios of control tissue were lowered to values far below one due to postmortem changes greatly reducing tissue concentrations of RNA. No detailed characterization of RNA was attempted. The nuclear DNA content of tumor cells reached values equivalent to chromosomal hexadekaploidy. This was in sharp contrast to control data from an Abrikossoff tumor of the oral cavity and from a neurohypophyseal tumorette (“choristoma”), respectively, displaying diploidy only associated with a much lesser increase of cytoplasmic RNA and proteins. Qualitative lipid studies were consistent with a marked active demyelination of the tumor centre as indicated by a severe reduction of cerebrosides and sulfatides and the presence of cholesterol esters. In addition there was a striking loss of phosphatidylethanolamine and a lesser one of sphingomyelin of white matter of both the tumor-stricken and the contralateral unaffected hemispherical regions, possibly suggesting a generally disturbed metabolism of myelin. It is not clear whether these general changes were resulting from the presence of the unilateral tumor or from precocious cerebral involution.

Progressive neurogene Muskelatrophie bei neuroaxonaler Dystrophie mit Rosenthalschen Fasern

SummarySince the age of 4, a young man suffered from a slowly progressive neurogenic atrophy of muscles of the distal type. At the age of 24 he unexpectedly died in alcoholic intoxication. Anatomical findings: No damage of the large nerve-cells in the anterior horn. Generalised neuroaxonal dystrophy in the central and peripheral nervous system, which differs from all the forms of naD known up to now by their combination with uncountable Rosenthal fibers in the brainstem and the periventricular and perivascular borderregions. We suspect a dysmetabolical process concerning the neuronal as well as the glial metabolism, which in spite of tendency of generalisation has clinically (hitherto) only shown up its secondary effect of neurogenic atrophy of the distal muscles.

Experimentelle Untersuchungen zur Wernickeschen Encephalopathie

SummaryThe tissue changes, in the experimentally produced acute and subacute Wernicke-syndrome in pigeons and in rats, are characterised by primary hydropic swelling of glial and neuronal cell processes. Apparently there is no initial disturbance of the blood brain barrier. The spongy necrosis with tissue breakdown and myelin degeneration occurs specially in the advanced stages of the lesion. We did not find any obvious damage of capillary basal membrane or the specific alteration of glial cell bodies as observed byCollins in his chronic stage of experiment. From our preliminary autohistoradiographic studies it can also be concluded that there is a lack of glial proliferation in the acute stage of experimental Wernickesyndrome.ZusammenfassungDie Gewebsveränderungen beim akut bis subakut ausgelösten experimentellen Wernicke-Syndrom der Taube und der Ratte sind gekennzeichnet durch eine primäre hydropische Schwellung gliöser und neuronaler Fortsätze im Neuropil. Eineinitiale Schädigung der Bluthirnschranke liegt offenbar nicht vor. In fortgeschrittenen Stadien kommt es zu einer spongiösen Nekrose mit Zusammenbruch des Gewebszusammenhanges und Markscheiden-degeneration. Im Gegensatz zu den mehr chronischen Versuchen vonCollins haben wir weder eindeutige Veränderungen der Capillarbasalmembran noch eine primäre spezifische Alteration gliöser Perikarien festgestellt. Nach unseren bisherigen autohistoradiographischen Untersuchungen fehlt auch eine wesentliche Gliazellproliferation in diesen akuten Stadien.

Histochemische Untersuchungen an den „ghost-cells” beim experimentellen Neurolathyrismus

ZusammenfassungDer experimentelle Neurolathyrismus ruft bei Mäusen, Ratten, Kaninchen und Katzen gleichartige Veränderungen hervor. Die bausteinhistochemische Untersuchung der ”ghost-cells” ergab einen hohen Gehalt an Eiweißkörpern, die aromatische Aminosäuren und Neuraminsäure enthalten. Außerdem ließen sich geringe Mengen neutraler Mucopolysaccharide und Lipoide nachweisen. Der Kohlenhydrat- und Lipoidgehalt liegt unter dem des Cytoplasmas der Vorderhornzellen. Die fädigen Strukturen, die wahrscheinlich ein Äquivalent der elektronenmikroskopisch nachgewiesenen Hyperplasie filamentärer Strukturen in den „Geisterzellen” sind, erweisen sich als besonders eiweißreich. Fermenthistochemisch läßt sich in den körnigen Strukturen, die wahrscheinlich den Mitochondrien entsprechen, eine Aktivität der Succinodehydrogenase und ATP-ase feststellen. Die fädigen Strukturen verfügen über eine schwache Aktivität von unspezifischen Esterasen. Für die Anwesenheit von RNS und DNS ergibt sich kein Anhalt. Die histochemischen Befunde erlauben eine Abgrenzung der „Geisterzellen” gegen Auftreibungen des Axoplasmas, die bei anderen, den Stoffwechsel des Neuroplasmas schädigenden Erkrankungen auftreten. Es wird vermutet, daß der experimentelle Neurolathyrismus zu einer irreversiblen Stoffwechselschädigung im Bereich der Eiweißkörper des Neuroplasmas führt.SummaryExperimentally produced neurolathyrism shows identical changes in mice, rats, rabbits and cats. The qualitative histochemical examination of the “ghost-cells” shows high amounts of proteins including aromatic amino acids and neuroaminic acid. Also small quantities of neural mucopolysaccharides and lipids are found. The content of carbohydrates and lipids is less than that of the cytoplasm of the anterior horn cells. The thread-like structures containing high quantities of protein probably correspond to the hyperplastic filamentous structures of ghost-cells seen in electron microscopy. In the granular structures, probably corresponding to mitochondria, enzyme-histochemical activity of succinic dehydrogenase and ATP-ase is demonstrable. The thread-like structures show low activity of unspecific esterases. RNS and DNS are not present. The histochemical findings permit a differentiation between “ghost-cells” and axonal swellings as found with other metabolic disturbances of the neuroplasm. Experimental neurolathyrism is suggested producing an irreversible metabolic disorder of protoplasmic proteins.

Neurosekretorisches Ganglienzell-Choristom in der Adenohypophyse

Report on a blastomatous dysgenesia (choristoma) with dystopic accumulation of neurosecretoric nerve-cells in the anterior lobe of hypophysis of a 65 years old woman without clinical symptoms.SummaryReport on a blastomatous dysgenesia (choristoma) with dystopic accumulation of neurosecretoric nerve-cells in the anterior lobe of hypophysis of a 65 years old woman without clinical symptoms.

Ein bisher kaum bekanntes gliogenes Melanin des Gehirns („Cerebellares Gliamelanin“)

Melanosis of the dentate nucleus is an extremely rare condition in which pigment is formed within the cytoplasm and cytoplasmic processes of astrocytes in the dentate nucleus and the cerebellar granular cell layer. The pigment occurs as irregular polygonal structures of rather homogeneous appearance unlike granular neuromelanin located within neurons of the substantia nigra. The diameter of these pigment masses may reach 30 Μm or more. Their absorption of visible light increases steadily towards the shorter wavelengths, and the material is virtually opaque in the violet and ultraviolet region, resembling melanin in this respect. Since the absorption spectrum described by Rabl exhibited a small peak at 525 nm, he regarded the pigment as the hemoglobin derivative pentdyopent. We were unable, however, to confirm this observation. On X-ray diffraction the pigment produced a sharp reflex at 4.93 å as did synthetic melanin prepared from dopamine (but not melanin prepared from serotonin). These observations supported the assumption made by others based on histochemical evidence, that the pigment in the dentate nucleus may belong to the group of melanins. Presumably the glial melanin somehow arises from the metabolic pathway leading to DOPA. An astrocytic site of melanin formation other than in the cerebellum has not been previously described, and this melanin differs in appearance from the granular neuromelanin found in neurons in the substantia nigra. Thus “cerebellar glial melanin” contrasts with neuromelanin of the substantia nigra both in its site of formation and in its morphology. The underlying cause of the glial melanin formation in the cerebellum is not known. There are six cases in the world literature, 5 females and 1 male, ranging in age from 58 to 103 years. Involutional alterations in metabolism related to endocrine factors may possibly play an important part. To the best of our knowledge cerebellar melanosis is of no clinical relevance.

Morphological feedback effect on the nucleoli of the neurons in the nucleus arcuatus (infundibularis) to hypophyseal hypogonadism in juvenile haemochromatosis

SummaryCase report of a man of 22 with juvenile haemochromatosis and hypogonadotropic hypogonadism. There is evidence of siderosis of the basophil cells of the hypophysis, atrophy of the testicles with disappearance of Leydig cells and alterations in the nucleoli of the neurones with enlargement, vacuolation and multiplication limited to the nucleus arcuatus tuberis. The nucleolar changes in this hypothalamic centre are interpreted as a feedback effect. They are comparable to matching alterations in the hypertrophy of the nucleus subventricularis (Sheehan and Kovács 1966) in post-partum hypopituitarism.

[Cerebral granular cell tumor in the rat after intraperitoneal application of aflatoxin b1 during pregnancy (author's transl)].

On a rat, which has spontaneous died 12 months after 4 times i.p. application of aflatoxin during pregnancy, there has been found a frontal tumor barely of the size of a pepper-corn which came out from the leptomeninx. A comparison to the Abrikossoff tumor concerning the light- and electron-microscope as well as the nucleic-acid concentration is justified. The protein content of the granula of the tumor cells is higher than the values known in the granular-cell myoblastoma of man.On a rat, which has spontaneous died 12 months after 4 times i.p. application of aflatoxin during pregnancy, there has been found a frontal tumor barely of the size of a pepper-corn which came out from the leptomeninx. A comparison to the Abrikossoff tumor concerning the light- and electron-microscope as well as the nucleic-acid concentration is justified. The protein content of the granula of the tumor cells is higher than the values known in the granular-cell myoblastoma of man.

Chronische infantile zentrale pontine Myelinolyse vom multifokalen Typ mit sekundären Capillarcalcinosen und Hypoxieschäden

SummaryThis study reports on a case of extremely chronic course of central pontine myelinolysis (multifocal type) with proliferation of glial fibres and asiderotic calcinosis of capillaries in a 2 8/12 years old girl. Since the first weeks of life there were observed periodic states of emesis, rumination and diarrhoe with hyperpyretic toxicosis, dehydration, exsiccosis, decrease in weight, cyanosis and decentralisation of circulation. Failure of drive, apathic states, statomotoric retardation, atonicastatic symptoms changing with extrapyramidal-pyramidal signs and loss of speech developed progressively since the eighth month. There were bilateral symmetrical lesions in the spinal cord, medulla, central grisea (without pallidum), cerebellum (without dentatum), and hippocampus. Glial fibres and intramural asiderotic calcinosis in the extracellular space of the vascular walls were only found in the burnt-out lesions, but not in the florid glialdystrophic demyelinated areas. The missing of Fe2+ in the concrements is caused by the youth of the patient. Besides the glial-dystrophic process there were fresh and old hypoxic foci in the cerebral and cerebellar cortex. It is assumed, that this burnt-out process of the multifocal-lesion-type of central pontine myelinolysis was caused by the eminently chronic course of periodic states of emesis, diarrhoe, dehydration and exsiccosis, decrease of weight, hyperpyretic toxicosis and decentralisation of circulation.