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J A Hainfellner

Publications and source records attributed to J A Hainfellner.

At least 19 recordsLinked to original sources
PubMed1999

Deposition of disease-associated prion protein involves the peripheral nervous system in experimental scrapie.

There is some evidence that the peripheral nervous system (PNS) is involved in the pathogenesis of transmissible spongiform encephalopathies (TSEs). The TSE-specific abnormal prion protein (PrP(sc)) is considered as surrogate marker for infectivity. We traced the deposition of PrP(sc) by immunocytochemistry in sheep and hamsters inoculated intraperitoneally with scrapie. The trigeminal, dorsal root, celiac, thoracic, and nodose ganglia contained ganglion cells and fewer satellite cells with prominent granular PrP(sc) deposition. As a novel deposition pattern, punctate deposits in adaxonal location were seen along nerve fibers of peripheral nerve adjacent to ganglia. Such prominent involvement of the PNS in two different experimental scrapie models emphasizes the need to consider the PNS in natural scrapie and other TSEs including bovine spongiform encephalopathy as potential source of infectivity.

Animals↗
PubMed1999

Disease associated prion protein may deposit in the peripheral nervous system in human transmissible spongiform encephalopathies.

There is increasing evidence indicating involvement of the peripheral nervous system (PNS) in the pathogenesis of transmissible spongiform encephalopathies (TSEs). Immunocytochemically detectable deposits of TSE-specific abnormal prion protein (PrP(sc)) are considered as a surrogate marker for infectivity. We used anti-PrP immunocytochemistry to trace PrP(sc) deposition in spinal and enteric ganglia, and peripheral nerve in Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia. Discrete PrP(sc) deposits were detectable only in a few posterior root nerve fibers in an adaxonal location in one of nine CJD and the one GSS patients examined. Follicular dendritic cells of the gut and enteric nervous system were not labeled. Thus, PrP(sc) may spread to the PNS in different forms of human prion disease. In contrast to our observations in experimental scrapie (Groschup et al., Acta Neuropathol, this issue), the deposits were scant. Possible explanations for this discrepancy comprise strain difference, or centripetal (experimental scrapie) versus centrifugal (sporadic and genetic human prion diseases) spread of PrP(sc), resulting in different patterns and amounts of PrP(sc) accumulation in the PNS.

Adult↗
PubMed1999

Deposition of the prion protein (PrP) during the evolution of experimental Creutzfeldt-Jakob disease.

We studied the immunocytochemical distribution of the prion or proteinase-resistant protein (PrP) during the evolution of experimental Creutzfeldt-Jakob disease (CJD) in mice. Fifty-one brains were collected up to 22 weeks following intracerebral inoculation with the Fujisaki strain of the CJD agent. Slides were also immunostained for apolipoprotein E (apoE) and glial fibrillary acidic protein. Vacuolar changes with focal astrocytosis first occurred around the needle track at week 2 and later spread along white matter tracks. Until week 12, changes were asymmetrical, affecting more the side of inoculation. Spongiform change and astrogliosis spread subsequently to the gray matter. Time course and intensity of spongiform change and immunocytochemistry for PrP were discrepant: in most brain regions, severe vacuolation preceded immunocytochemically detectable PrP accumulation. PrP deposits in form of small dots were first detectable at week 6 in the area surrounding the needle track. After week 7, plaque-like amorphous PrP deposits were observed in white matter pathways. Finally, PrP was detectable also in basal ganglia and in the dorsal hippocampus (week 13) and in the neocortex (week 17), as the synaptic type of PrP immunopositivity. In the hippocampus, diffuse PrP deposits paralleled spongiform change, while in the cortex severe vacuolation was accompanied only by weak synaptic PrP deposits. Immunocytochemically detectable apoE was restricted to compact plaque-type PrP deposits after week 15. We conclude that disease-specific neuropathology spreads from the needle track along white matter pathways towards the gray matter; in this model, there is some discrepancy between development of tissue pathology and immunocytochemically detectable deposition of PrP. Immunocytochemically detectable apoE deposition follows PrP accumulation.

Animals↗
PubMed1999

Fatal familial insomnia: a new Austrian family.

We present clinical, pathological and molecular features of the first Austrian family with fatal familial insomnia. Detailed clinical data are available in five patients and autopsy in four patients. Age at onset of disease ranged between 20 and 60 years, and disease duration between 8 and 20 months. Severe loss of weight was an early symptom in all five patients. Four patients developed insomnia and/or autonomic dysfunction, and all five patients developed motor abnormalities. Analysis of the prion protein (PrP) gene revealed the codon 178 point mutation and methionine homozygosity at position 129. In all brains, neuropathology showed widespread cortical astrogliosis, widespread brainstem nuclei and tract degeneration, and olivary 'pseudohypertrophy' with vacuolated neurons, in addition to neuropathological features described previously, such as thalamic and olivary degeneration. Western blotting of one brain and immunocytochemistry in four brains revealed quantitative and regional dissociation between PrP(res)(the protease resistant form of PrP) deposition and histopathology. In the cerebellar cortex of one patient, PrP(res) deposits were prominent in the molecular layer and displayed a peculiar patchy and strip-like pattern with perpendicular orientation to the surface. In another patient, a single vacuolated neuron in the inferior olivary nuclei contained prominent intravacuolar granular PrP(res) deposits, resembling changes of brainstem neurons in bovine spongiform encephalopathy.

Adult↗
PubMed1999

No complementation between TP53 or RB-1 and v-src in astrocytomas of GFAP-v-src transgenic mice.

Human low-grade astrocytomas frequently recur and progress to states of higher malignancy. During tumor progression TP53 alterations are among the first genetic changes, while derangement of the p16/p14ARF/RB-1 system occurs later. To probe the pathogenetic significance of TP53 and RB-1 alterations, we introduced a v-src transgene driven by glial fibrillary acidic protein (GFAP) regulatory elements (which causes preneoplastic astrocytic lesions and stochastically astrocytomas of varying degrees of malignancy) into TP53+/- or RB-1+/- mice. Hemizygosity for TP53 or RB-1 did not increase the incidence or shorten the latency of astrocytic tumors in GFAP-v-src mice over a period of up to 76 weeks. Single strand conformation analysis of exons 5 to 8 of non-ablated TP53 alleles revealed altered migration patterns in only 3/16 tumors analyzed. Wild-type RB-1 alleles were retained in all RB-1+/-GFAP-v-src mice-derived astrocytic tumors analyzed, and pRb immunostaining revealed protein expression in all tumors. Conversely, the GFAP-v-src transgene did not influence the development of extraneural tumors related to TP53 or RB-1 hemizygosity. Therefore, the present study indicates that neither loss of RB-1 nor of TP53 confer a growth advantage in vivo to preneoplastic astrocytes expressing v-src, and suggests that RB-1 and TP53 belong to one single complementation group along with v-src in this transgenic model of astrocytoma development. The stochastic development of astrocytic tumors in GFAP-v-src, TP53+/- GFAP-v-src, and RB-1+/- GFAP-v-src transgenic mice indicates that additional hitherto unknown genetic lesions of astrocytes contribute to tumorigenesis, whose elucidation may prove important for our understanding of astrocytoma initiation and progression.

Animals↗
PubMed1999

A novel phenotype in familial Creutzfeldt-Jakob disease: prion protein gene E200K mutation coupled with valine at codon 129 and type 2 protease-resistant prion protein.

A novel phenotype of familial Creutzfeldt-Jakob disease (CJD) with mutated codon 200 of the prion protein gene (PRNP) coupled with the valine codon 129 (E200K-129V haplotype) has two features never observed in subjects carrying the pathogenic mutation coupled with the methionine codon 129 (E200K-129M haplotype): (1) plaque-like prion protein (PrP) deposits in the cerebellum and (2) type 2 protease-resistant prion protein (PrP(res)). This observation further underlines the role of codon 129 on the mutated PRNP allele in modulating the phenotype of familial prion diseases.

Aged↗
PubMed1999

[Acute symptom transverse laminectomy for a benign osteoclastoma of thethoracic spine--case report and review of the literature].

Benign osteoclastomas of the spine above the sacrum are uncommon lesions. Acute paraparesis as the presenting sign of disease is unusual and rarely described in the literature. We report on the case of a 41 yrs old male who underwent acute T3-5 laminectomy for spinal cord decompression from a T4 expansive mass lesion with locally destructive growth. Although a malignant lesion was suspected, definitive histologic examination disclosed a benign osteoclastoma. Therefore, elective trans-thoracic total vertebrectomy T4 with ventral stabilization was performed to allow for marginal total resection of the tumor and reconstruction of the spine. Twenty-four months after the procedure the patient has made a good neurologic recovery with no evidence of tumor recurrence.

Acute Disease↗
PubMed1998

Development of HIV encephalitis in AIDS and TNF-alpha regulatory elements.

Tumor necrosis factor-alpha (TNF-alpha) appears to play an important role in HIV encephalitis (HIVE). TNF2, a polymorphism of TNF-alpha, associates with higher levels of TNF-alpha and severe manifestations of some infections. We studied 44 acquired immunodeficiency syndrome (AIDS) patients with autopsy-proven HIVE and/or HIV leukoencephalopathy (HIVLE) (HIVE/LE) and 30 AIDS patients without HIVE/LE. TNF2 did not associate with presence of HIVE/LE (p > 0.5). Moreover, the TNF-alpha regulatory element TTATTTAT within the 3'-untranslated region was intact in HIVE/LE brains, and HLA-DR3 did not associate with HIVE/LE. Other host factors or, more likely, viral factors may be responsible for the development of HIVE/LE.

AIDS Dementia Complex↗
PubMed1998

[Creutzfeldt-Jakob disease in a dura transplant recipient: first observation in Austria].

Dura mater grafts can lead to Creutz-feldt-Jakob disease (CJD) as late complication (dura-CJD). So far 61 dura-CJD cases have been described worldwide. We report here the first dura-CJD case in Austria. A 50-year-old man had a traumatic open frontobasal skull fracture with tearing of dura mater in 1977. Reconstructive surgery used Lyodura (braun Melsungen AG, BRD). Lyodura was derived from pooled cadaveric dura. Ten years after the dural transplantation, the patient developed gait ataxia, paresthesia of both legs, myoclonus and visual disturbance. CT was unremarkable. EEG showed diffuse unspecific changes. The patient died 5 months after onset of disease. Neuropathological examination showed typical histopathology of CJD. Immunocytochemistry detected typical type prion protein (PrP) deposits and scattered PrP plaques in cerebral and cerebellar cortex, basal ganglia and spinal cord. Cerebellar white matter contained numerous PrP miniplaques. This pattern is unusual for sporadic CJD, but is similar to that in CJD after human growth hormone treatment. In our patient and 13/19 earlier described cases with dural graft covering the cerebrum ("central inoculation"), cerebellar disturbance was the initial symptom. Therefore, cerebellar signs are characteristic as initial symptoms in iatrogenic CJD, irrespective of central (cerebral dura mater graft) or peripheral inoculation (e.g., human growth hormone treatment). These data do not support the hypothesis that primary cerebellar symptoms in iatrogenic CJD after peripheral inoculation reflect migration of the infectious agent from the periphery via spinal cord and cerebellum to the cerebrum.

Brain↗
PubMed1998

Coexistence of Alzheimer-type neuropathology in Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease (AD) share clinical, neuropathological, and pathogenetic features. To investigate eventual mutual influences, we screened prominently affected neocortex from 110 neuropathologically proven CJD patients for Alzheimer-type pathology with anti-beta/A4, Bielschowsky and anti-tau (immuno)stains. The neuropathological classification of Alzheimer-type pathology was made according to the CERAD criteria. Results were controlled by comparison with Alzheimer-type changes in sections from the same cortical areas in 110 sex- and age-matched non-demented control patients. For comparison, the control patients were also classified according to the CERAD neuropathology criteria as if they had been demented. Alzheimer-type tissue changes as in definite and probable CERAD AD occur in 10.9% of the CJD patients and 19.1% of control patients (P=0.11). The median age of CJD and control patients with CERAD AD is 72 and 68 years, respectively, which differs significantly from the median ages of 64 and 63 years, respectively, in the non-AD/CJD and non-AD control patients. Since CERAD criteria include "presence of other neuropathological lesions likely to cause dementia", an AD diagnosis in CJD patients (all of whom are demented) is solely based on densities of neuritic plaques. Similar Alzheimer-type changes in even higher frequency, however, are also present in elderly non-demented controls. Thus, the coexistence of Alzheimer-type pathology in CJD most likely represents an age-related change. Deposits of prion protein (PrP) frequently accumulate at the periphery of beta/A4 plaques. The presence of beta/A4 amyloid in the brain may influence PrP morphogenesis.

Aged↗
PubMed1998

Frameless stereotactic-directed tissue sampling during surgery of suspected low-grade gliomas to avoid histological undergrading.

Detection of anaplastic tumor foci for precise grading of gliomas is crucial for prognostic assessment and appropriate postoperative treatment planning. To avoided undergrading in large suspected low-grade gliomas, we employed frameless sterotaxy during open surgery for tissue sampling of radiologically suspected anaplastic foci. In nine patients (mean age 44 years, range 10-67) with large supratentorial suspected low-grade gliomas (32.4 ccm mean vol, range 17.9-68.6 ccm) with small contrast enhancing areas (7.7% mean of total volume, range 0.7-15.3%), a neuronavigation system with a pointer device (Easy Guide System Philips) or a navigating microscope (MKM System Zeiss) was used to target small enhancing tumor parts for cytological investigation during open surgery. Consecutive cytological smears revealed anaplastic tumor foci in all patients, correlating with neuroradiologically demonstrated small contrast enhancing areas, although biopsies from all other tumor parts showed low-grade tumors. Final neuropathological diagnosis confirmed anaplasia within the neuroradiologically suspected low-grade gliomas in all patients (2 grade IV, 5 WHO grade III and 2 grade II-III tumors, WHO classification). In our experience frameless stereotactic-directed intraoperative tissue sampling during open surgery of large suspected low-grade gliomas helps to identify small anaplastic areas in mostly large low-grade tumors, and therefore, permits optimum planning of postoperative treatment.

Adolescent↗
PubMed1998

Transgenic mice as research tools in neurocarcinogenesis.

Transgenic animal models for neurocarcinogenesis have provided significant insights into the molecular mechanisms underlying carcinogenic processes, including those which affect the nervous system. In view of the very rapid pace of acquisition of knowledge, it is not possible to cover all transgenic mouse models for neural tumors. Instead, this article discusses some of the most important technical innovations for manipulation of the mammalian genome (notably the various methods for targeted genome modifications, as well as the technology for introducing large DNA fragments into the germ line of mice), and presents a selection of the transgenic mouse models which are proving most promising for furthering our understanding of the pathogenetic basis of cancer in the nervous system.

Animals↗
PubMed1998

[Epidemiology of transmissible spongiform encephalopathies (prion diseases) in Austria].

Between 1969 and 1996, transmissible spongiform encephalopathy was definitely diagnosed by autopsy and/or biopsy in 98 Austrian patients. The yearly incidence increased significantly in past years (1996: 1.41 cases per million inhabitants). This increase likely results from increased awareness in the medical community and effectuation of the diagnostic autopsy. The new variant of Creutzfeldt-Jakob disease (CJD), probably transmitted from bovine spongiform encephalopathy (BSE), has not occurred in Austria. The percentage of patients older than 70 years increased until 1989 and declined slightly thereafter. One patient received a dura mater graft 11 years before death. Another patient had familial CJD with a glutamatelysin mutation on codon 200 of the prion protein (PrP) gene PRNP. One more patient died from Gerstmann-Sträussler-Scheinker disease (GSS), three patients from fatal familial insomnia (FFI). Another patient received intramuscular injections of a purified RNA preparation (Regeneresen) produced from various organs including brain. The age at death symmetrically distributes around a median of 64 years. Two CJD patients were unusually young (27 and 30 years). Most patients (72.7%) died within 6 months of disease. Retrospectively, 81% of patients had clinical diagnostic criteria of probable or possible CJD (52% probably and 29% possible). In 19%, clinical criteria for CJD were not fully met. There is no case clustering with specific professional groups or geographic areas. However, residents of Vienna, or Vienna and Lower Austria, respectively, had CJD diagnosed twice or three times more frequently than the rest of the country, indicating regionally differing qualities of case retrieval.

Adolescent↗
PubMed1997

Progressive multifocal leukoencephalopathy in AIDS: initial and follow-up CT and MRI.

We sought to determine the value of follow-up CT and MRI in patients with acquired immuno-deficiency syndrome (AIDS) and progressive multifocal leukoencephalopathy (PML). We reviewed 50 CT and 19 MRI examinations performed in 21 biopsy- or autopsy-proven cases of PML; 17 patients had follow-up examinations (mean time 5.9 weeks). The radiological examinations were correlated with pathological findings at autopsy. On initial imaging studies, 73 lesions were found. On follow-up, the most striking feature was rapid progression in both size and number of the lesions (from a mean of 3.2 to 6.9 per patient). One third of the patients showed increasing mass effect. A central area suggesting necrosis, of variable size, was found in 12/16 patients. Autopsy revealed macroscopic necrotic changes in the lesions in 11/16 patients.

AIDS Dementia Complex↗
PubMed1997

Distribution of parvalbumin-immunoreactive neurons in brain correlates with hippocampal and temporal cortical pathology in Creutzfeldt-Jakob disease.

There is a distinctive pattern of hippocampal involvement in Creutzfeldt-Jakob disease (CJD) and evidence for selective vulnerability of GABAergic neurons in experimental and human prion disease. We studied hippocampus and temporal cortex from human CJD and control autopsy brains and surgical cryptogenic temporal lobe epilepsy specimens for distribution and density of parvalbumin (PV) and calbindin-D28K (Cal) -positive neurons that are subpopulations of GABAergic neurons. Pathology was evaluated semiquantitatively in 8 regions in 23 CJD brains for severity of spongiform change, astrogliosis and pathological prion protein deposition. In CJD, pathology was severe in pre-parasubiculum and temporal cortex, and little or absent in CA1-4; PV+ neurons were severely reduced or absent in all cases, whereas Cal+ neurons were largely preserved. In controls, the density of PV+ neurons was highest in pre-parasubiculum and temporal cortex, and lowest in CA1-4. In cTLE, loss of PV+ neurons was seen only in CA1-4. The diffuse and severe loss of PV+ neurons in CJD, and the topographical correlation of tissue lesioning in CJD with density of PV+ neurons in controls suggest selective vulnerability and early loss of this subset of inhibitory neurons in CJD. This might relate to characteristic CJD symptoms such as myoclonus and the distinctive EEG pattern.

Adult↗
PubMed1997

Pathology and immunocytochemistry of a kuru brain.

We report here results of modern staining techniques including anti-prion protein (PrP) immunocytochemistry to a set of archival brain specimens of a 16 year-old male who died from kuru in 1967. Brain suspensions transmitted disease to chimpanzees and New World monkeys. The PrP gene is homozygous for valine at the polymorphic codon 129. Histology shows neuronal loss, spongiform change, and astrogliosis. Lesions are maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, striatum, and thalamus, and are accentuated in middle and deep cerebral cortical layers. PrP accumulates as diffuse synaptic type deposits and mostly unicentric plaques. PrP deposition is maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, basal ganglia, and cerebellar cortex. Plaques are prominent in the striatum, thalamus, and granular layer of cerebellar cortex. Meticulous examination reveals only rare "florid" plaques with surrounding vacuolation. We conclude that 1) pathology including immunomorphology of PrP deposition in this kuru brain is within the lesion spectrum of Creutzfeldt-Jakob disease although plaques are unusually prominent and widespread; 2) kuru does not share the neuropathological hallmarks of the new Creutzfeldt-Jakob disease variant recently reported in the UK and France; 3) topographic prominence of PrP deposition parallels that of spongiform change and/or astrogliosis.

Adolescent↗