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Biomedical subjects

H Budka

Publications and source records attributed to H Budka.

At least 127 records · Page 7Linked to original sources
PubMed1995

Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases).

Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD--sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immunoreactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Sträussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population). Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spongiosis. This includes status spongiosus ("spongiform state"), comprising irregular cavities in gliotic neuropil following extensive neuronal loss (including also lesions of "burnt-out" CJD), "spongy" changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission.

Creutzfeldt-Jakob Syndrome↗
PubMed1994

Patterns of oligodendroglia pathology in multiple sclerosis.

Patterns of inflammation, demyelination and oligodendrocyte pathology were studied in acute multiple sclerosis and during early and late exacerbations of chronic multiple sclerosis. Cells within lesions were identified by immunocytochemistry with markers for T lymphocytes, macrophages, oligodendrocytes and astrocytes. In addition, in situ hybridization for proteolipid protein mRNA was used to identify myelinating and myelin supporting oligodendrocytes. Degenerating cells in the lesions were detected by DNA fragmentation in cell nuclei. The inflammatory reaction in all three types of multiple sclerosis lesions was shown to be dominated by T lymphocytes and macrophages. In late chronic multiple sclerosis lesions, a significant increase in the number of immunoglobulin producing plasma cells was found in infiltrates as compared with acute and early multiple sclerosis lesions. In all three types of multiple sclerosis, confluent plaques of demyelination were found to be present. In acute multiple sclerosis, demyelination was found to be associated with extensive destruction of other tissue elements, including oligodendrocytes, astrocytes and axons, but even in these destructive lesions a considerable number of oligodendrocytes was preserved and at disposal therefore, for rapid remyelination. During early exacerbations of chronic multiple sclerosis, selective demyelination was associated with almost complete preservation of oligodendrocytes in the majority of cases. Correspondingly, a high number of remyelinating lesions was present at that stage of disease. In lesions developing late after onset of multiple sclerosis, demyelination generally accompanied extensive destruction and loss of oligodendrocytes. In these lesions, remyelination was sparse and restricted to lesional borders. The observed patterns of cell death suggest that in some cases oligodendrocytes, in others myelin sheaths are the primary target of the destructive process. Our data indicate that the type and amount of inflammation, de- and remyelination, and of tissue damage vary between different forms of multiple sclerosis and between different stages of the disease, possibly reflecting different pathogenic mechanisms in a disease spectrum.

Adult↗
PubMed1993

Clonal expansion of hypermutated measles virus in a SSPE brain.

Nucleotide sequence analysis was carried out to study genes encoding the matrix (M) protein of measles virus (MV) from several regions of the brain of a case of subacute sclerosing panencephalitis. This analysis revealed the presence of MV with "wild-type" sequences as well as variants which had undergone at least five biased hypermutation events (U to C and A to G in the positive strand sequences). Despite the presence of MV variants with genes encoding the intact matrix protein open reading frame, M protein could not be detected in any of the brain regions. The distribution of virus variants was studied by cDNA cloning and sequence analysis and by in situ hybridization. The hypermutated viruses appeared to expand clonally throughout the brain of patient B.

Adult↗
PubMed1993

Neuronal damage in the cerebral cortex of AIDS brains: a morphometric study.

Using stereological methods, two cerebral cortical areas from AIDS brains were investigated. Neuronal density, profile area of neurons, and perikaryon volume fraction were measured and compared to age-matched control brains. In the fronto-orbital cortex (area 11) of AIDS brains, a significant loss of neurons was seen. The perikaryon volume fraction was likewise decreased. The size of neurons did not differ between control and AIDS brains. In patients with clinical signs of progressive dementia and in brains with human immunodeficiency virus (HIV)-specific neuropathology (HIV-leukoencephalopathy and/or HIV-encephalitis) as compared to patients lacking these features, a small decrease in neuronal density was noted but this difference did not reach the level of statistical significance (P = 0.16). In the superior parietal lobule (area 7) of AIDS brains, no loss of nerve cells was noted. AIDS patients with progressive dementia and brains with HIV-specific neuropathology showed no difference in neuronal densities as compared to those without such features. We conclude that the fronto-orbital cortex, in contrast to the parietal cortex, is mainly damaged in AIDS brains. Neuronal loss was not significantly correlated with development of dementing symptoms and of HIV-specific neuropathology.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Uncommon types of polyglucosan bodies in the human brain: distribution and relation to disease.

The significance of the development of polyglucosan bodies (PBs) in the CNS is incompletely understood. We present the clinicopathological features of three autopsy cases with numerous PBs other than the common corpora amylacea or Lafora bodies. The first patient had pleomorphic PBs in the neuronal processes of pallidum and substantia nigra which, thus, are consistent with Bielschowsky bodies. Bielschowsky bodies involved also the hypothalamus and tegmentum of midbrain and medulla. The present case was the first not associated with any clinical symptoms. The second patient also had incidental Bielschowsky bodies in the external pallidum, substantia nigra, and pallidothalamic, pallidonigral and nigrostriatal tracts. Additionally, unique clusters of small PBs appeared in the cerebral cortex, putamen, pallidum, and caudate nucleus. Immunostaining suggested that these small clustered PBs were located in the cytoplasm and processes of astrocytes. Ultrastructurally, these clustered PBs were in agreement with previous descriptions of PBs. The third patient had adult polyglucosan body disease. Most PBs in the white matter were corpora amylacea situated in astrocytic processes or axons. In the gray matter, many pleomorphic PBs resembling Bielschowsky bodies occurred in neuronal processes. In the peripheral nervous system, a few PBs were seen in myelinated axons.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Immunostaining for proliferating cell nuclear antigen: its role in determination of proliferation in routinely processed human brain tumor specimens.

Alcohol- and formalin-fixed, paraffin-embedded samples of 71 brain tumors (35 gliomas, 22 metastatic carcinomas, 8 meningiomas and 6 other tumors) were investigated by immunocytochemistry with three different monoclonal antibodies against proliferating cell nuclear antigen (PCNA)/cyclin (19A2; 19F4; PC10). PC10 was found to work best; it is applicable to both alcohol- and formalin-fixed tumor samples. PCNA labeling indices (LIs) were compared in the same tumors with LIs obtained by Ki-67 immunostaining of frozen sections and by in vitro incubation with bromodeoxyuridine (BrdUrd); in the latter preparations, BrdUrd LIs could be compared with PCNA LIs in the very same areas of serial sections. In gliomas, PCNA LIs were 0.7-80.2% (mean 31.7%), in metastases 0-76.0% (mean 47.8%), and in meningiomas 0-53.0% (mean 19.3%). In general, PCNA LIs were highly significantly correlated with Ki-67 LIs (P = 0.0002) and BrdUrd LIs (P = 0.0001). However, when tumor subgroups are considered, only gliomas show a significant correlation with Ki-67 and BrdUrd LIs. Despite this statistical correlation, PCNA expression was out of proportion to proliferation indices as determined by both other methods in almost one third of all brain tumors. Immunocytochemistry for PCNA produces a broad spectrum of staining intensity of labeled nuclei, whose number is dependent upon the sensitivity of the immunocytochemical technique used. Thus, inter-observer and inter-laboratory variabilities in PCNA LI determination may occur. Overlapping of PCNA LIs between tumor subgroups of varying malignancy further limits the informational value for the individual case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Microglia is a component of the prion protein amyloid plaque in the Gerstmann-Sträussler-Scheinker syndrome.

The microglial cell has been demonstrated as component of the cerebral amyloid plaque of Alzheimer's disease. Involvement of microglia in plaques of another cerebral amyloidosis, the Gerstmann-Sträussler-Scheinker syndrome (GSS), has found little attention. We examine here the presence of microglia in GSS plaques by immunohistochemistry and transmission electron microscopy. Paraffin sections from five brains of patients with GSS were immunolabelled with antibodies against prion protein, A4/beta amyloid protein, ferritin, leukocyte common antigen, HLA-DR, CD 68, and the MAC387 epitope for microglia and monocytes/macrophages; microglia was also labelled with the Ricinus communis agglutinin-1 lectin. Such (immuno)labelling demonstrated many delicate cell processes and occasional somata within and around prion protein plaques in all GSS brains. Microglial immunoreactivity was strongest with anti-ferritin and variable with anti-macrophage antibodies. Ultrastructural examination of brain tissue from one autopsy and one biopsy of GSS identified microglial cells in close proximity of amyloid plaque fibrils. Our observations demonstrate microglia as an important component of the amyloid plaque in GSS and suggest a major role for microglia in processing and deposition, or at least organization, of prion protein amyloid. Thus, plaques in both transmissible and non-transmissible cerebral amyloidoses seem to develop via similar pathogenetic mechanisms, irrespective of differences in etiology and molecular composition of the amyloid.

Brain↗
PubMed1993

Fatal encephalitis caused by concomitant infection with tick-borne encephalitis virus and Borrelia burgdorferi.

We describe a 38-year-old farmer from the southwestern archipelago of Finland where both tick-borne encephalitis (TBE) virus and Borrelia burgdorferi are endemic. He presented with fever and headache, developed severe meningoencephalitis in 3 days, and, after 1 month, died without regaining consciousness. High titers of IgG and IgM antibodies to TBE virus were present in both serum and CSF. Serology for Borrelia was negative. Autopsy revealed necrotizing encephalitis and myelitis with involvement of the dorsal root ganglion. With use of polymerase chain reaction tests, segments of two separate genes of B. burgdorferi were amplified from the patient's CSF. This case demonstrates that the possibility of dual infection should be considered for patients residing in geographic areas where Ixodes ticks may carry both the TBE virus and B. burgdorferi. We believe that the most severe damage in this case was caused by TBE virus rather than by B. burgdorferi. Nevertheless, the coinfection might have contributed to the fatal outcome that has not been previously observed in Finnish patients with TBE.

Adult↗
PubMed1993

Astroglial changes in the cerebral cortex of AIDS brains: a morphometric and immunohistochemical investigation.

Astroglial changes in the cerebral cortex of AIDS brains were analysed by means of morphometry. Astrocytes with and without immunoreactivity for glial acidic protein (GFAP) were counted and their size was measured. In the two investigated cortical areas (frontal and parietal), a similar reaction pattern of astroglia was observed. The total number of astrocytes (i.e. GFAP-positive and GFAP-negative astrocytes) did not differ between control and AIDS brains. However, the number of GFAP-positive astrocytes was significantly increased in AIDS brains, while the number of GFAP-negative cells was significantly reduced. Nuclear size of GFAP-negative and GFAP-positive astrocytes was significantly increased. The reaction pattern of cortical astrocytes in AIDS seems to be characterized by GFAP production in protoplasmic astroglia as well as by hypertrophy of all astrocytes.

AIDS Dementia Complex↗
PubMed1993

[Hypernephroma and associated AL-amyloidosis with polyneuropathy in monoclonal gammopathy].

Malignant neoplasms may have secondary (reactive, AA), amyloidosis as a sequel. Among carcinomas, this is most frequent with hypernephroma. We report a 60-year-old male patient with progressive polyneuropathy and monoclonal gammopathy of the kappa type. A renal tumor was histologically diagnosed as hypernephroma at nephrectomy. The patient did not improve postoperatively and died three and a half months later from pulmonary embolism. Autopsy revealed a systemic amyloidosis, predominantly with prominent deposits in peripheral nerves. Immunohistochemical staining demonstrated the amyloidosis as of the primary (AL) type, rather than of the expected AA type. A plasmocytoma was not detected, either clinically or at autopsy. We assume here a coincidental rather than causal connection between the hypernephroma and the monoclonal gammopathy with AL amyloid and the neuropathy.

Amyloid↗
PubMed1992

Tubulovesicular structures in Creutzfeldt-Jakob disease.

By electron microscopy tubulovesicular structures (TVS) have been consistently observed in brain tissue of transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy and experimentally induced, but not naturally occurring, Creutzfeldt-Jakob disease (CJD). For the first time we report here the presence of TVS in human brains with CJD as detected by transmission electron microscopy. TVS were observed in all three CJD specimens (two biopsies, one autopsy), but they were rare and were found only in one or two location(s) per grid. TVS were seen in distended pre- and postsynaptic terminals and measured approximately 35 nm in diameter; they were smaller and of higher electron density than synaptic vesicles. Their occurrence in all types of transmissible spongiform encephalopathies irrespective of the affected host and the strain of the infectious agent suggests their biological significance.

Aged↗
PubMed1992

Subacute diencephalic angioencephalopathy: an entity similar to angiodysgenetic necrotizing encephalopathy and Foix-Alajouanine disease.

A previously healthy 58-year-old man developed neurological illness with progressive dementia, hallucinations, central motor and vegetative impairment which led to death in 14 weeks. Autopsy revealed lesions in a symmetrical centrencephalic distribution. Inner cerebral veins and arteries were surrounded by extravasation of plasma and perivascular haemorrhage and were thickened by fibrous scarring and muscle fibre proliferation. Necrotized blood vessels were also found. The parenchyma was damaged by incomplete to complete necrosis. The age and sex of the patient, the progressive clinical course, the increase of cerebrospinal fluid protein, and the histopathology of the lesion show some similarities to angiodysgenetic necrotizing encephalopathy and spinal Foix-Alajouanine disease.

Angiodysplasia↗
PubMed1992

Presence, distribution and spread of productive varicella zoster virus infection in nervous tissues.

Nervous tissue lesions were retrospectively studied for detection of productive varicella zoster virus (VZV) infection in 33 autopsied cases, including 19 herpes zoster (HZ) (10 trigeminal, nine spinal) and 14 cases of nodular brainstem encephalitis without HZ. Immunocytochemistry for VZV antigens and in situ hybridization with a biotinylated VZV DNA probe were used on formol-fixed paraffin sections. Peripheral and central nervous system, skin and striated muscle were investigated in serial sections; available tissue blocks, however, varied between cases. Varicella zoster virus production (both antigen and DNA) in nervous tissue was found in HZ cases but only of short survival after a rash of up to 7 wks (eight out of 12 patients). Varicella zoster virus was visualized in nerve cells, glial cells, Schwann cells and blood vessels. In the central nervous system (CNS), VZV was detected in trigeminal nuclei (one out of 10 brains) or disseminated nodular brainstem lesions (one out of 10 brains), in subependymal microvessels (one out of 10 brains) or vasculitic arteries (two out of 19 brains or spinal cords). In the peripheral nervous system (PNS), VZV (DNA and antigen) was found in neurons and satellite cells of sensory ganglia (four out of seven cases with sampling of ganglia), and in damaged nerve fibres including a muscle nerve in one case; myositis with VZV in affected muscle fibres was found in the latter case. In nodular brainstem encephalitis, one case contained VZV within nodular lesions. We conclude that (i) VZV neural spread is suggested by detectable virus in ganglia, nerve fibres and CNS target nuclei; (ii) haematogenous spread of VZV is suggested by detection of virus in CNS microvessels and in disseminated brainstem encephalitis; (iii) VZV myositis may occur in zosteric myotomes; and (iv) VZV is a possible agent in nodular brainstem encephalitis.

Adult↗
PubMed1992

Morphological spectrum, distribution and clinical correlation of white matter lesions in AIDS brains.

This paper analyses the histopathological characteristics and the topographical distribution of 'pure' HIV-associated white matter lesions of the brain in 18 AIDS patients at autopsy; it includes a time-controlled correlation of neuropathology to clinical staging of the AIDS dementia complex. Three distinct lesion types can be delineated: 1 Vacuolar myelin damage (n = 15) in the hemispheric and interhemispheric white matter, in projection fibre tracts, and in intracerebral segments of cranial nerves III, VII, and VIII; 2 Angiocentric foci (n = 14), disseminated randomly in the white matter; 3 HIV leukoencephalopathy (n = 14), as previously defined, seen predominantly in the hemispheric white matter. As a sole lesion type, HIV leukoencephalopathy is found in two cases, while vacuolar myelin damage and angiocentric foci always occur in combination with one or both other types of pathology. Patients with advanced AIDS-dementia complex consistently show severe and combined white matter pathologies at autopsy. We conclude that, in addition to the previously defined features of diffuse HIV leukoencephalopathy, vacuolar myelin damage and angiocentric foci are significant and frequent components of white matter pathology in AIDS autopsies. This reflects the multitude of pathogenetic factors which co-operate in damaging the brain in AIDS. The advanced AIDS dementia complex correlates with the combined and severe white matter lesions.

Acquired Immunodeficiency Syndrome↗