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K Jellinger

Publications and source records attributed to K Jellinger.

At least 91 records · Page 5Linked to original sources
PubMed1987

Histochemistry of MAO-A and MAO-B in the locus coeruleus of the Mongolian gerbil.

A coupled peroxidation technique for localization of monoamine oxidase (MAO-A and MAO-B), applied to post-mortem fixed tissue of the locus coeruleus of the Mongolian gerbil is demonstrated. Tyramine hydrochloride, beta-phenylethylamine and 5-hydroxytryptamine creatinine sulphate were used as substrates, 1-deprenyl and clorgyline served as specific inhibitors. All three substrates stained the neurons of locus coeruleus in the absence of inhibitor. In the presence of 1-deprenyl, tyramine hydrochloride and 5-hydroxytryptamine creatinine sulphate were metabolized, whereas in the presence of clorgyline no reaction with either substrate could be observed. Immunocytochemical staining of tyrosine hydroxylase (TH) was employed as comparison.

Animals↗
PubMed1987

Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's, Parkinson's, and Huntington's diseases.

Because dopamine D2 receptors are known to be elevated in schizophrenic brain striata, this study examined whether a similar dopamine receptor elevation occurred in other diseases including neuroleptic-treated Alzheimer's and Huntington's diseases. The average D1 density in postmortem striata from Alzheimer's patients was 17.6 +/- 0.1 pmol/g, similar to an age-matched control density of 16.6 +/- 0.4 pmol/g. The average D1 density in schizophrenia patients was 19.0 +/- 0.6 pmol/g, similar to the age-matched control density of 17.9 +/- 0.6 pmol/g. In Parkinson's disease patients, however, the D1 receptor density was elevated, with values of 22.8 +/- 1.2 pmol/g (in patients not receiving L-DOPA) and 19.6 +/- 1.5 pmol/g (in patients receiving L-DOPA) compared to the age-matched control density of 16.0 +/- 0.4 pmol/g. The D2 receptors in Alzheimer's striata averaged 13.4 +/- 0.6 pmol/g (in patients who had not received neuroleptics), almost identical to the control density of 12.7 +/- 0.3 pmol/g. The average D2 density in neuroleptic-treated Alzheimer's striata was 16.7 +/- 0.7 pmol/g, an elevation of 31%, the individual values of which had a normal distribution. In Parkinson's disease patients, the D2 densities were elevated in tissues from patients not receiving L-DOPA (19.9 +/- 1.5 pmol/g in putamen and 14.8 +/- 1.2 pmol/g in striatum) compared to the age-matched control values of 13.0 +/- 0.4 pmol/g and 12.6 +/- 0.3 pmol/g, respectively. In Huntington's disease patients, the D2 density averaged 7.5 +/- 0.4 pmol/g in patients who had not received neuroleptics, but was 10.3 +/- 0.6 pmol/g in those who had. Although all of the D1 and D2 densities in each of the above diseases and subgroups revealed a normal distribution pattern, the D2 densities in schizophrenia displayed a bimodal distribution pattern, with 48 striata having a mode at 14 pmol/g, and the other 44 striata having a mode at 26 pmol/g. Thus, compared to the neuroleptic-induced and unimodal elevations in D2 of 31% in Alzheimer's disease and 37% in Huntington's disease, the schizophrenic striata with a mode of 26 pmol/g (105% above control) appear to contain more D2 receptors than can be accounted for by the neuroleptic administration alone.

Adult↗
PubMed1987

Neuropathological aspects of infantile spasms.

A review of the neuropathological findings in 50 personal autopsy cases and in the available literature (214 confirmed cases) of infantile spasms demonstrates that this type of early infantile epilepsy occurs in a wide range of cerebral lesions caused by various noxae during different stages of brain development. With regard to morphology and the presumed time of occurrence of the CNS lesions, four groups can be distinguished: (1) embryofetal lesions, including a) cerebral malformations or developmental disorders-agyria-pachygyria (lissencephaly), micrencephaly, micropolygyrias, (hemi)megalencephaly, agenesis of corpus callosum, tuberous sclerosis, heterotopias, cortical microdysplasias, b) metabolic disorders (leukodystrophies, neurolipidoses, spongy dystrophies, Leigh and Alpers diseases, aminoacidopathies); (2) perinatal and postnatal encephalopathies, e.g. polycystic brain, diffuse and lobar sclerosis, ulegyrias, white matter and basal ganglia scars, status marmoratus, hippocampal sclerosis, and cerebellar atrophy; (3) combined embryofetal (developmental) and perinatal or postnatal brain lesions, particularly association of microdysplasias with secondary anoxic or vascular changes; (4) acute vascular and inflammatory brain injuries; (5) cases without definite brain pathology. Evaluation of the available data indicates that embryo-fetal lesions alone or accompanied and/or superimposed by perinatal or postnatal lesions account for about 61% of the cases confirmed by autopsy, in which infantile spasms can be regarded as fetal epilepsies, while a smaller group is featured by perinatal or postnatal lesions occurring in early age, i.e. affecting the immature brain. Similar lesions are observed in cases showing transition of West syndrome to Lennox syndrome. Negative pathology findings in a small number of cases do not necessarily implicate negative pathobiology.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1987

Neuropathological substrates of Alzheimer's disease and Parkinson's disease.

The pathology of Alzheimer's disease (AD) and Parkinson's disease (PD) is characterized by degeneration of certain vulnerable neuronal populations that display several types of cytoskeletal abnormalities (Alzheimer-type lesions and Lewy bodies, respectively). These may serve as diagnostic markers, although they can be found in both types of disorders and, less frequently, in brains of normal aged individuals. AD pathology shows a preponderance for hippocampal, neocortical, and forebrain cholinergic systems; the hallmark of PD is damage to the nigrostriatal dopaminergic system. Both disorders show frequent involvement of subcortical projection systems that can be similar in quality and distribution, with similar multiple neuromediator dysfunction. The results of morphometric studies of some subcortical nuclei in AD and PD are reported and related with neurochemical data. In addition to classical forms of AD and PD, both types of lesions can coexist suggesting an increased risk of PD in patients with AD and vice versa. The basis for an association between the two disorders is unknown. Many AD cases with signs of PD have additional PD pathology, while cortical Alzheimer lesions may be seen in demented PD patients. However, dementia in PD does not imply coexistent cortical AD pathology; prominent subcortical lesions alone, or in combination with cortical AD pathology, may occur. AD and PD may show some differences in the primary locus of degenerative changes in specific cortical and subcortical neuronal systems, but the causative factors, mutual relations, and relative contributions to the clinical syndromes remain to be elucidated.

Aged↗
PubMed1987

Cellular action of MAO inhibitors.

Sites of action of monoamine oxidase (MAO) inhibitors in the human brain were analyzed by studying the distribution of the respective MAO subtype, MAO-A or -B. Blood brain barrier (BBB), glial cells and neurons of several brain areas were examined with biochemical and immunocytochemical methods. Whereas MAO-A was localized in microvessels and neurons of locus ceruleus, MAO-B was present predominantly in neuronal cells of dorsal raphe nucleus. The neurons of substantia nigra revealed no immunohistochemically detectable MAO. Astrocytes expressed both subtypes and were observed in all cortical areas examined and all over the brain stem including medulla reticular formation, pontine reticular formation, reticular formation of mesencephalon, midbrain reticular formation, red nucleus, substantia nigra, caudate nucleus and putamen (sections according to DeArmond et al., 1976). MAO activity in several brain areas seems mostly to be due to astrocytes rather than to neuronal cells. As MAO inhibitors have beneficial effects in the treatment of malfunctions of aminergic transmitter systems (Johnstone and Marsh, 1973; Robinson et al., 1973; Birkmayer et al., 1977; Knoll, 1981; Zarifian, 1984; Riederer and Youdim, 1986) and a large amount of MAO activity seems to be localized in brain astrocytes, the function of glial cells especially with regard to their neuromodulating capacity should be focused in more detailed research in future.

Aged↗
PubMed1986

Neuropathology of Rett syndrome.

Autopsy studies in 8 girls with the Rett syndrome dying between 4 and 15 years showed: Diffuse cerebral atrophy/micrencephaly, with a decrease in brain weight by 13.8 to 33.8% of age-matched controls, apparently related to the duration of the disorder; Mild, but inconsistent diffuse cortical atrophy without developmental disorders apart from occasional microdysgenesis (three cases), but increased amounts of neuronal lipofuscin, and occasional mild astrocytic gliosis; Mild, but inconsistent spongy changes in cerebral and cerebellar white matter, optic nerve (two cases), and myelinated fascicles of the brainstem tegmentum, without signs of dys- or demyelination, and apparently different from the spongy myelinopathy common to aminoacidopathies; Most conspicuous was an underpigmentation of the substantia nigra which contained many fewer well-pigmented neurons for age (53-73%), and fewer pigmented granules per neuron, while the total number of nigral neurons and the triphasic substructure of neuromelanin were normal for age. No pathologic changes were seen in locus coeruleus, nucleus basalis of Meynert, and nucleus dorsalis raphe; Electron microscopy of autopsy material from an 11-year-old girl showed increased amounts of neuronal lipofuscin without signs of a storage disorder. Reactive and degenerating axons in the caudate nucleus were possibly related to the nigral changes, suggesting some dysfunction of the dopaminergic nigro-striatal system, while the synaptic organization of the neostriatum appeared unaffected. Peripheral nerve from a patient dying in advanced stage showed increased numbers of unmyelinated (regenerated?) axons, with almost no demyelination and few remyelinated axons, suggesting axonal degeneration rather than hypomyelination, but exogenous factors (malnutrition) cannot be excluded. The pathogenetic mechanisms of the morphologic brain lesions and their relations to clinical and neurochemical findings in Rett syndrome are unknown and deserve further intensive investigations.

Adolescent↗
PubMed1986

Dopamine D2 receptor density remains constant in treated Parkinson's disease.

D2 dopamine receptor densities were measured in postmortem samples of the caudate nucleus and putamen from 36 parkinsonian patients. The relationship between the age of the patient, duration of the disease, and duration of L-dopa therapy versus density of brain D2 dopamine receptors was examined using [3H]spiperone. Receptor density in parkinsonian tissues was constant over the age range of 56 to 90 years, as was the case for control tissues. Density did not change with duration of disease up to 24 years. Treatment with L-dopa did not cause progressive reduction in receptor density. The diminished clinical response in the final stages of Parkinson's disease is not due to receptor dropout, and must depend on other factors.

Age Factors↗
PubMed1986

Multifocal spinal angiosarcoma after chordotomy.

A male aged 60 is reported who, 5 years after chordotomy at the Th 2/3 level, developed acute paraplegia of the legs and a sensory transverse lesion due to an extradural tumour of the Th 1-4 level. Neuropathology revealed transverse necrosis of the thoracic spinal cord (Th 1-4) due to an intradural tumour at the upper thoracic and lumbar spinal levels, the thoracic malignancy arising at the site of the previous chordotomy, with a suture being observed within the tumour mass. Histology, positive immunostaining of tumour cells with Factor VIII antigen, a specific marker of endothelial cells and the ultrastructural demonstration of Weibel-Palade bodies in endothelial cells of the tumour vessels suggested a malignant mesenchymal tumour of angiosarcoma type presumably arising from the spinal meninges, and broadly invading the spinal cord. The usual relation of this extremely rare intraspinal vasoformative malignancy to previous chordotomy is discussed.

Antigens↗
PubMed1986

Vascular malformations of the central nervous system: a morphological overview.

Vascular malformations of the central nervous system (C.N.S.) are classified by size, location, and morphologic type, distinguishing capillary telangiectasias, cavernous malformations, venous angiomas, arteriovenous malformations (AVMs) including varix of the great vein of Galen, and other vascular malformations (e.g. Sturge-Weber syndrome). The morphology and predominant location pattern of the different types of vascular malformations in the brain and spinal cord, and their embryology are reviewed. In the brain and its coverings, all types mainly AVMs and venous angiomas do occur, representing 5-9% of all intracranial space-occupying lesions and 20-40% of the sources of surgically treated intracranial hemorrhages. 50-80% of the angiomas are located in the cerebral hemispheres, 10-18% in central brain areas (basal ganglia, internal capsule, choroid plexus), and 10-30% in the posterior fossa. The major types of cerebral vascular malformations are described with reference to their anatomical features, location, chief arterial and venous supply, and prominent complications. Spinal vascular malformations, accounting for 3 to 12% of spinal space-occupying lesions, include vertebral, extradural, dural, subpial and intramedullary angiomas which occur as isolated or complex vascular anomalies and may involve various covering layers at the same level. The preferential occurrence of angiomas on the dorsal surface of the cord and in the caudal regions is related to the embryologic development of spinal vasculature. Frequent association of spinal angiomas (20-25%) with other vascular anomalies and dysplasias emphasizes their hamartomatous nature and developmental origin. Spinal angiomas include capillary telangiectasias with extra- or intradural and, rarely, intramedullary location, cavernomas, mainly arising in vertebral bodies, venous angiomas, mainly located in vertebral bodies and in the extradural space, and AVMs constituting the commonest type, that may affect both the pial and radicular vessels and can penetrate into the cord. They present as simple AV fistulas, cirsoid angiomas with localized vascular plexuses and large complex convolutions ("juvenile" type). The complications of spinal angiomas include subarachnoid hemorrhage, rare epidural hematoma, hematomyelia, compression lesions of the cord and roots, and ischemic changes causing chronic progressive radiculomyelopathy, previously referred to as Foix-Alajouanine syndrome. Chronic damage to the cord and spinal roots results from pressure effects, thrombosis of the abnormal vessels, disorders of venous drainage, and "steal" phenomena related to the vascular anomalies.

Arteriovenous Malformations↗
PubMed1985

Multifocal neuropathy with vasculitis in hypereosinophilic syndrome. An entity or drug-induced effect?

A 56-year-old male with a 2-year history of bronchial asthma, together with pulmonary infiltration and marked eosinophilia, developed a subacute multifocal sensorimotor neuropathy. Electrodiagnostic studies demonstrated both multifocal and generalized nerve involvement. Sural nerve and muscle biopsies revealed axonal degeneration with almost complete loss of myelinated fibres, lymphomononuclear vasculitis of interstitial vasa nervorum without eosinophils, and neurogenic atrophy of muscle without angiitis. Although eosinophilia decreased drastically with corticosteroid treatment, neuropathy rapidly progressed to total disability. The patient died from pulmonary embolism 4 months after the onset of neurological signs. Autopsy disclosed vasculitis of epineurial vessels of peripheral nerves and severe axonal neuropathy, particularly of the lower limbs, without vasculitis or other inflammatory lesions in any other organ system, including the lungs. Retrospective analysis revealed that the onset of pulmonary infiltration and eosinophilia coincided with the administration of cromolyn sodium (Intal), which is known to produce PIE syndrome (pulmonary infiltration and eosinophilia), vasculitis and allergic granulomatosis, while multifocal neuropathy with vasculitis appears not to have been reported in connection with this substance.

Biopsy↗
PubMed1985

Gliosarcomas: histological, immunohistochemical, ultrastructural, and tissue culture studies.

Thirty-nine cases of gliosarcomas, two initiating as fibrosarcomas, 25 as mixed gliomas and sarcomas, and 12 as anaplastic gliomas with secondary sarcomas, were studied by light microscopy, immunohistochemistry, using GFAP, factor VIII/RAg, and Ulex europaeus I agglutinin (UEA I), electron microscopy and tissue culture. GFAP was found variably positive in the glial areas; F VIII/RAg and UEA I, markers of both normal and neoplastic endothelial cells and their derivatives, were found in vessels of both gliomatous and sarcomatous parts of GS, less intensive in hyperplastic glomeruloid structures and, with decreasing intensity, in adjacent fibrosarcomatous areas, while UEA I, giving stronger reaction than F VIII/RAg, was occasionally demonstrated in sarcomatous cells. In vitro studies confirmed previous data of a separate growth of glial and mesenchymal cells with a divergent migratory speed. Electron microscopy demonstrated the frequent close admixture of glial and mesenchymal tumor cells, which showed the feature of either fibrosarcoma or angiosarcoma. The frequent resemblance of the latter with endothelial cells was supported by the occasional demonstration of Weibel-Palade-like bodies in both vascular endothelial and adjacent sarcomatous cells. These observations confirm the hypothesis that at least part of the sarcomatous components in many GS originate from vascular endothelial proliferation and obviously represent the final stage of a process starting with the endothelial hyperplasia in anaplastic gliomas.

Adolescent↗
PubMed1985

Comparison of benzodiazepine receptor binding in membranes from human or rat brain.

Specific high affinity binding of [3H]flunitrazepam to membranes from human brain was stimulated by gamma-aminobutyric acid (GABA), pentobarbital, 1-ethyl-4-(isopropylidene-hydrazino)-1H-pyrazolo[3,4b]pyridine-5-carboxy lic acid ethyl ester hydrochloride (SQ 20009) and avermectin B1a and was unaffected by 2 microM 4'-chlorodiazepam (Ro 5-4864) indicating that [3H]flunitrazepam in human brain as well as in rat brain predominantly binds to benzodiazepine receptors specific to brain, which was associated with a GABA receptor and several modulatory binding sites for drugs. The potency of several selective and non-selective ligands for benzodiazepine receptors for inhibition of the binding of [3H]flunitrazepam was compared in membranes from human or rat brain cerebellum, hippocampus and cerebral cortex. It was demonstrated that all these compounds, derived from different chemical structures, had a remarkably similar potency for inhibition of the binding of [3H]flunitrazepam in the corresponding regions of the human or rat brain. However, irreversible labelling of benzodiazepine binding sites with [3H]flunitrazepam and subsequent SDS-polyacrylamide gel electrophoresis and fluorography revealed more photolabelled protein bands in human than in rat cerebellum and hippocampus. The results seem to indicate that, although the pharmacological properties of reversible binding of [3H]flunitrazepam are remarkably similar in membranes from rat or human brain, the molecular heterogeneity of benzodiazepine binding sites is even greater in human than in rat brain.

Animals↗
PubMed1985

[Changes in and modulation of receptor activity in hepatic encephalopathy].

In hepatic encephalopathy (HE) brain uptake of large neutral amino acids is impaired with tryptophan crossing the blood brain barrier (BBB) to a much larger extent than all other competing amino acids (AA). The disturbance in the steady-state of transmitter is paralleled to the change of their kinetic data. This is reflected by an increase in serotonin (5-HT) synthesis and turnover, while the number of post-synaptic 5-HT1-binding sites is decreased, 5-HT2-receptor activity is dropping to a much smaller extent. On the other hand, presynaptic dopaminergic activity remains unchanged with no change in D2-receptor activity. Valine (VAL) improves the postsynaptic 5-HT function via modulating activity due to a regulatory mechanism at the membranal level in vitro and ex vivo. Furthermore, VAL leads to a significant reduction of serum ammonia (NH4+) and brain NH4+ concentration. VAL is able to antagonize the binding density diminishing effects of NH4+ on 5-HT binding sites. This effect could be characterized by the measurement of VAL binding sites being 5 to 10 fold higher than the number of leucin (LEU)-sites. Considering the chemical bonds involved in the attachment of biogenic amines and aminoacids (Schiff-bases equilibria) the modulating action of NH4+ on neural transmission may be clarified. Tryptamine can displace the postsynaptic binding of 5-HT in brain tissue and is a possible antagonist to physiological and pharmacological effects of 5-HT. The dynamic changes of the kinetic behaviour of tryptamine-binding might demonstrate a compensating effect as shown in an increase of tryptaminergic receptor activity. As a working hypothesis, the different relative strengths of electron-pair donor and -acceptor sites of both compounds are suggested to their complementary physiological interaction. GABA, an inhibitory transmitter of the CNS is diminished in its maximal binding capacity in severe HE and is independent of NH4+ influence. Furthermore, glutamate and aspartate-receptors decrease in experimentally induced hepatic coma. L-LEU shows modulating effects of glutamine binding. Glycin-activity is increased, while naloxone- and D-ala2-methionine-encephalinamid binding are not different from controls. These data demonstrate a different influence of various brain receptors and binding sites by HE and indicate a differentiated disturbance of (neuronal) membrane activity. Therefore disturbed interneuronal dynamics might be important pathophysiological mechanisms underlying hepatic coma.

Ammonia↗
PubMed1984

Bimodal distribution of dopamine receptor densities in brains of schizophrenics.

The dopamine hypothesis of schizophrenia was examined by measuring the density of dopamine receptors in the postmortem brains of 81 control subjects and 59 schizophrenics from four different countries. The densities of dopamine receptors in the tissues from the schizophrenic patients had a bimodal distribution in the caudate nucleus, putamen, and nucleus accumbens. One mode occurred 25 percent above the control density, and a second mode occurred at a density 2.3 times that of the control density for all three regions. Although almost all the patients had been medicated with neuroleptics, the two modes had the same dissociation constant for the labeled ligand used, suggesting that the neuroleptic doses were similar for the two populations of schizophrenics. The results thus provide direct evidence for two distinct categories of schizophrenia.

Antipsychotic Agents↗
PubMed1984

Cerebral granulomatous angiitis with atypical features.

A case of cerebral granulomatous angiitis of the left temporal lobe mimicking a brain tumour is presented. Following surgical removal of a glioma-imitating mass, histological examination disclosed a granulomatous vasculitis. Treatment consisted of dexamethasone given in tapering doses for 5 days after surgery. Clinical and morphological differences from other reported cases of granulomatous angiitis of the nervous system are described.

Adult↗
PubMed1984

Metastasis of solid tumors in extraocular muscles.

Three autopsy cases with discrete metastatic involvement of one or several extraocular orbital muscles by disseminated amelanotic melanoma (one case) and lobular mammary adenocarcinoma (two cases) associated with extensive meningeal involvement are reported. Clinical ocular symptoms including pain, exophthalamus, and diplopia occurred 6 months to almost 5 years after resection of the primary tumor; in two cases CT scan showed spindle-like enlargement of orbital muscles. Pathologic examination disclosed solid localized metastatic deposits in several extraocular muscles of one (breast carcinomas) or both orbits (melanoma), with diffuse invasion of striated muscle, but without necrosis, inflammation, or involvement of other orbital adnexa, eye ball, optic nerves, or orbital bone. Since no continuous invasion of orbital or intraocular structures by diffuse meningeal blastomatosis was histologically observed, rare metastatic involvement of extraocular muscles via hematogenic route is suggested.

Breast Neoplasms↗