PubMed Health⌕ Search

Biomedical subjects

K Jellinger

Publications and source records attributed to K Jellinger.

At least 73 records · Page 4Linked to original sources
PubMed1989

Tau and ubiquitin immunoreactivity at different stages of formation of Alzheimer neurofibrillary tangles.

In his original 1911 publication Alois Alzheimer classified neurofibrillary tangles (ANT) into three morphologically defined subgroups according to their stage of maturation. The present study shows that changes in the morphological appearance of ANT during their maturation process are accompanied by changes in their antigenic profile. As shown by several immunocytochemical studies these abnormal phosphorylated microtubule-associated protein tau and of ubiquitin. In this study, immunoreactivity for the altered tau is not only seen in a subset of tangles but also in the cytoplasm of some nerve cells lacking ANT, which we believe to be at a stage of neuronal alteration preceding the formation of compact tangles (Stage 0 tangles). Similar numbers of Stage 0 tangles are present in the brains of age-matched non-demented individuals as in Alzheimer cases, but are absent in young controls lacking ANT. In extracellular "ghost tangles", the ultimate stage of neurofibrillary degeneration, immunoreactivity for tau is accessible to antibodies only when tissue sections are pretreated with formic acid to uncover the binding sites. In contrast to tau, presence/accessibility of an epitope residing on residues 50-65 of ubiquitin recognized by a monoclonal antibody raised to paired helical filaments (3-39) increases during the maturation of ANT and is most pronounced in "ghost tangles". Appearance/uncovering of the 3-39 epitope and masking of tau reactivity during tangle maturation may reflect degradation or conformational changes in the pathological filaments due to their aging and the final loss of their parent nerve cells.

Aged↗
PubMed1988

[Infantile form of nemaline (rod inclusion) myopathy].

This paper reports the first Austrian case of infantile nemaline myopathy in a girl aged 19 years, presenting with congenital skeletal dysplasia, reduced body weight and slowly progressive limb girdle muscular atrophy, myopathic face and difficulty in swallowing. Electromyography revealed a combination of myopathic and neurogenic lesions, while electron microscopy of a muscle biopsy established the diagnosis. The patient's mother and two elder brothers showed no clinical features of the disease, but neurophysiological abnormalities were present, indicating an asymptomatic form of illness. The aetiology and pathogenesis of nemaline myopathy are unknown, but neurogenic factors cannot be excluded.

Adult↗
PubMed1988

Neuropathology of Rett syndrome.

Rett syndrome is an increasingly recognized progressive disorder in females, commencing in infancy and characterized by autistic behavior, gait ataxia, stereotyped movements, seizures and generalized growth and mental retardation, possibly associated with disorders of central biogenic amine synthesis. The gene locus and pathogenesis of Rett syndrome are unknown. Autopsy studies in nine girls dying between 4 and 17 years, and sural nerve and muscle biopsies from two girls aged 3 and 17 years showed: (1) diffuse cortical atrophy/micrencephaly, with a decrease in brain weight by 12% to 34% of age-matched controls, apparently related to the duration of the disorder; (2) mild diffuse cortical atrophy with increased amounts of neuronal lipofuscin and occasional mild gliosis, but without signs of a storage disorder; (3) underpigmentation of the zona compacta nigrae, which showed fewer well-pigmented neurons for age and fewer melanin granules per neuron, while total numbers of nigral neurons and the substructure of neuromelanin were normal for age. No pathological changes were seen in other transmitter-specific brain stem nuclei; (4) immunoreactivity for tyrosine hydroxylase was slightly reduced in nigral and hypothalamic neurons, and the pituitary gland showed decreased immunoreaction for prolactin and growth hormone; (5) ultrastructurally, in frontal cortex and caudate nucleus, isolated abnormal neurites and reactive or degenerative axonal swellings were seen; the latter are possibly related to the nigral changes, suggesting some dysfunction of the dopaminergic nigrostriatal system, which is supported by neurochemical data; (6) preliminary biochemical studies revealed increased beta-endorphines in thalamus and cerebellum; (7) peripheral nerves demonstrated increase in small fibers without demyelination and increased numbers of neurofilaments in axons, suggesting distal axonopathy, while skeletal muscle showed alterations in the sarcoplasmic reticulum with circular profiles in the Z-filaments. These nonspecific changes may be interpreted as early signs of denervation. The variety of lesions in the central, neuroendocrine and peripheral neuromuscular systems in Rett syndrome are discussed with regard to their clinical and biochemical significance.

Adolescent↗
PubMed1988

Reactivity of circulating antineuronal antibodies (CANA) on peripheral nervous system structures.

The appearance of circulating antineuronal antibodies (CANA) in patients with malignant tumors has been correlated with the occurrence of paraneoplastic neurological syndromes. However, the effect of CANA on the peripheral nervous system is poorly understood. The reactivity of sera from CANA-positive and -negative patients were investigated on cryostat sections of peripheral nerves and skeletal muscle, and on nerve tease-fiber preparations. Only CANA-positive sera showed staining of Schwann cell nuclei on cryostat sections, whereas nerve tease-fiber preparations and sections of skeletal muscle remained negative. Positive direct immunofluorescence of small cell lung cancer (SCLS) cells was confined to CANA-positive patients only. These findings suggest the existence of a common antigen between SCLC and Schwann cells.

Autoantibodies↗
PubMed1988

Homospecific activity (activity per enzyme protein) of tyrosine hydroxylase increases in parkinsonian brain.

Tyrosine hydroxylase (TH) contents in the caudate nucleus, putamen, and substantia nigra from control and parkinsonism brains were measured for the first time by a sandwich enzyme immunoassay. Both the TH protein content and TH activity (Vmax) were decreased in parallel in the parkinsonian brains as compared with those of the control brains. In contrast, TH "homospecific activity" (activity per enzyme protein) was significantly increased in the parkinsonian brains. The results indicate that the decrease of TH activity in parkinsonian brains is due to the decrease of TH protein content as a result of cell death. The increase in the "homospecific activity" of residual TH in parkinsonian brain suggests such molecular changes in TH molecules as result in a compensatory increase in TH activity.

Brain Chemistry↗
PubMed1988

Meningeal melanocytoma. Report of a case and review of the literature.

A primary localized, partly encapsulated melanotic tumour broadly attached to the occipital dura and tentorium was removed from a 27 year-old woman. It recurred almost four years later in the posterior fossa and was resected again. Although grossly resembling a meningioma, the tumour lacked the histological, immunocytochemical and ultrastructural features of meningiomas and was characterized by the presence of numerous melanosomes and premelanosomes in the cytoplasm of tumour cells and macrophages and was, therefore, classified as "meningeal melanocytoma". The clinical and pathological features of this and 15 other cases in the literature are reviewed. The neoplasm, mainly occurring in the posterior cranial fossa and spinal canal, may cause neurological deficits through expanding, but non-invasive growth. Its biological behaviour is variable, and recurrence may occur after incomplete resection, but transition into malignant melanoma has not been observed. Total resection of this rare pigmented tumour arising from the pial melanocytes is recommended.

Adult↗
PubMed1988

Topographic immunocytochemical mapping of monoamine oxidase-A, monoamine oxidase-B and tyrosine hydroxylase in human post mortem brain stem.

Immunocytochemical demonstration of monoamine oxidase-A, monoamine oxidase-B and tyrosine hydroxylase was performed in the human brain stem using monoclonal antibodies to monoamine oxidase-A and monoamine oxidase-B and polyclonal antibodies to tyrosine hydroxylase. In most of the brain areas examined, except the serotonergic dorsal nucleus of raphe, the noradrenergic locus coeruleus and the dorsal efferent nucleus of vagus, tyrosine hydroxylase-positive neurons were in greater number than monoamine oxidase-A-stained or monoamine oxidase-B-stained neurons. The dorsal nucleus of raphe showed no tyrosine hydroxylase immunoreactivity, but reacted positively to serotonin- and monoamine oxidase-B antibodies, while monoamine oxidase-A staining was moderate. In none of the investigated brain areas did neurons exclusively react with monoamine oxidase-B antibodies without expressing monoamine oxidase-A in a few neurons, while in some areas neurons expressed both monoamine oxidase-A and tyrosine hydroxylase (locus coeruleus; dorsal efferent nucleus of vagus). The oculomotor nucleus stained only with monoamine oxidase-A antibodies, substantia nigra neurons reacted only with tyrosine hydroxylase antibodies. Glial staining in most of the brain areas examined seemed, with slight differences, to have the same intensity with monoamine oxidase-A and monoamine oxidase-B antibodies used. No glial staining was obtained with tyrosine hydroxylase antibodies.

Aged↗
PubMed1988

Tyrosine hydroxylase activity in caudate nucleus from Parkinson's disease: effects of iron and phosphorylating agents.

Tyrosine hydroxylase (TH) activity of human postmortem brain tissues from controls and patients with Parkinson's disease (PD) was examined in the presence of Fe2+ and phosphorylation agents, such as cyclic AMP, exogenous protein kinase, calcium plus calmodulin (Ca2+-CaM), and ATP. TH activity from parkinsonian tissue was increased by 48% with statistical significance in the presence of exogenous protein kinase. Cyclic AMP alone had no effect, whereas Ca2+-CaM increased the activity by only 10%. The presence of acetylcholine resulted in a slight decrease in enzyme activity. Human TH was stimulated 13.17-fold in the presence of 1 mM Fe2+. For iron dependence, no significant differences could be shown for the Km values of TH in striata of PD, while the activity of TH was half of that of controls. Here stimulation with 1 mM Fe2+ raised the activity of TH 11-fold. Stimulation of rat, gerbil, pig, and human caudate nucleus TH with Fe2+ shows remarkable species differences. In particular, the sensitivity of human TH to stimulating processes is noteworthy. H2O2 decreases TH activity only at high concentrations. Species differences are noted for the combined incubation of Fe2+ and H2O2. In the gerbil caudate nucleus, H2O2 does not prevent the stimulating properties of Fe2+, while the pig shows a dose-dependent decline of TH activity. In conclusion, there are no significant changes in the stimulating properties of human caudate nucleus TH activity with Fe2+ in PD, while such differences are noted by using exogenous protein kinase. Furthermore, experimental evidence shows that TH activity declines at high concentrations of H2O2 only. Potentiation of this effect by Fe2+ seems to be species-dependent.

Aged↗
PubMed1988

Changes in cerebral receptors for gamma aminobutyric acid in patients with hepatic encephalopathy.

If the gamma-aminobutyric acid (GABA) inhibitory neurotransmitter system plays an important role in the mediation of hepatic encephalopathy (HE) in man, changes in the status of receptors for GABA in the brain may occur in patients with HE. To test this possibility, brains were obtained at autopsy from 11 patients who had died of causes unrelated to liver disease and from 11 patients who had died with chronic liver disease. Eight of the liver disease group had overt HE at the time of death. The specific binding of GABA to synaptic membranes isolated from frontal cortex was determined. Mean specific binding of GABA for patients with cirrhosis without overt HE was similar to that for control patients. In contrast, corresponding means for patients who had mild HE (stages I-III) and for patients who had severe HE (stage IV) were 45% higher (p less than 0.05) and 43% lower, respectively, than that for control patients. The mean specific binding of GABA was significantly greater for patients with mild HE than in patients with severe HE (p less than 0.025). Scatchard plots of the GABA binding data were curvilinear and consistent with a model of GABA receptors with two independent binding sites. Computer-assisted analysis of the binding data indicated that the altered GABA binding observed in patients with HE is attributable to changes in the affinity rather than the density of both GABA receptors (increased affinities in mild HE, and decreased affinities in hepatic coma). These findings are compatible with the hypothesis that alterations in GABAergic neurotransmission are associated with and contribute to the syndrome of HE in man.

Aged↗
PubMed1988

The pedunculopontine nucleus in Parkinson's disease, progressive supranuclear palsy and Alzheimer's disease.

Significant loss of neurons in the pedunculopontine nucleus pars compacta (PPNc), a putative cholinergic nucleus involved in modulating somatic motor activities, has been demonstrated in progressive supranuclear palsy (PSP) and Parkinson's disease but not in Alzheimer's disease. A morphometric study of this nucleus was performed in two cases of PSP and in a cohort of cases of Parkinson's disease, Alzheimer's disease, senile dementia of Alzheimer type (SDAT), and age-matched controls. In PSP a significant 60% neuronal loss in PPNc was associated with neurofibrillary tangles in 40 to 64% of the remaining neurons. In Parkinson's disease there was a significant decrease in cell numbers and density by 53 and 51%, respectively, with Lewy bodies involving 6 to 39% of all neurons. In Alzheimer's disease and SDAT, large neurons were reduced by 29 and 33.8%, respectively, with tangles in 9 to 38% of the remaining cells. The selective affection of this putative cholinergic nucleus in PSP and Parkinson's disease appears to be related to motor dysfunctions in these disorders.

Aged↗
PubMed1987

[Lisuride in the combination treatment of Parkinson disease].

Lisuride, a semisynthetic dopaminergic ergot derivative, was administered in 34 patients with Parkinson's disease (mean age 67.5 years, average duration of illness 7.1 years, mostly stage IV) in an average oral dosage of 1.2 to 1.5 mg (range 0.4 to 3.0 mg) in addition to basic treatment with levodopa and decarboxylase inhibitor. Duration of combined treatment was 3 to 44 months. Daily dose of levodopa could be reduced by 13 to 34%. In the short-term group (3 months) the total disability score improved by 50%, and in the long-term group (up to 44 months) by 46%, with improvement of rigidity, tremor, speech and repeated movements, less of bradykinesia. Similar to treatment with dopamine agonists, after 18 to 24 months, despite increased dosage of levodopa, a slight increase of some clinical features of parkinsonism, particularly bradykinesia and gait disorders, were observed. Daily fluctuation and on-off symptoms often improved in intensity, but were eliminated only in a small number of patients. Discontinuation of lisuride due to adverse effects was necessary in 17.6%. Often, however, preexisting adverse effects of levodopa therapy, particularly psychiatric complications, responded favorably. Lisuride is a new effective agent in the combination treatment of advanced stages of parkinsonism.

Adult↗
PubMed1987

Human brain dopamine receptors in children and aging adults.

Since spontaneous oral dyskinesias are more prevalent in the elderly, and since these movements may be controlled by the balance of brain dopamine D1 and D2 dopamine receptors, we measured the densities of these receptors in 247 postmortem brain striata. In childhood, the densities of D1 and D2 dopamine receptors in the brain striatum rise and fall together. After age 20 years, D1 receptors disappear at 3.2% per decade while D2 receptors disappear at about 2.2% per decade. Overall, therefore, the D1/D2 ratio falls with age. Since perioral motion in rats is dominated by a high D1/D2 ratio, the observed decline in the human D1/D2 ratio with age suggests that the perioral control mechanisms for humans and rats may be different.

Aged↗
PubMed1987

Adjuvant treatment of Parksinson's disease with budipine: a double-blind trial versus placebo.

Budipine, a new 4,4-diphenylpiperidine derivative, and placebo were administered three times daily to 31 patients with Parkinson's disease over a period of 12 weeks. All patients in the two treatment groups received levodopa (plus benserazide) at an optimum and constant dose for at least 2 months before the start of the study and throughout the trial. The additional administration of budipine (daily dose 60 mg) was excellently tolerated by 14 patients, while 2 patients left the study because of mental confusion at an early stage of the trial. The budipine group showed a 22% improvement on the Columbia Rating Scale (median score). Compared with the placebo group (4% improvement), there was a highly significant difference (P less than 0.01, one-tailed test). Of the three main symptoms of Parkinson's disease, the best effect was seen on tremor, and less pronounced effects on bradykinesia and rigidity. Owing to its long half-life (31 h) with little plasma level fluctuations, budipine appears to be an effective agent in the treatment of Parkinson's disease.

Aged↗
PubMed1987

Antineuronal antibodies in small cell lung carcinoma--a significance for paraneoplastic syndromes?

In recent years a cause-effect relationship between the existence of circulating antineuronal antibodies (CANA) and neurological paraneoplastic syndromes has been described by several authors suggesting specifity of such antibodies for paraneoplastic syndromes. The present study is a systematic approach to elucidate the significance of CANA in tumor patients. Forty patients with biopsy-proven small cell cancer of the lung (SCLC) were compared to 70 non-SCLC patients and 20 controls in respect to clinical and neurophysiological findings. CANA were found in 17 patients with SCLC. However, only one of these patients with SCLC and positive CANA displayed a sensory neuropathy of the Denny-Brown type, which appeared to be unrelated to CANA titers and oncological course. Contrary to recent reports, we were not able to confirm an association between the existence of CANA and an increased incidence of paraneoplastic neurological syndromes. These data suggest that the antineuronal antibodies appear to be specific for SCLC, but are not necessarily related to paraneoplastic neurological syndromes.

Aged↗