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Biomedical subjects

H Budka

Publications and source records attributed to H Budka.

At least 163 records · Page 9Linked to original sources
PubMed1990

Neuropathology of AIDS dementia. A review after 205 post mortem examinations.

109 brains were selected after the exclusion of those affected by space occupying lesions or opportunistic infections. All brains with HIV specificity (nodules with multinucleated cells and, at times, two peculiar kinds of myelin involvement) were atrophic (62%); nevertheless dementia had been mentioned only in the 55% of the corresponding autopsy requests. In agreement with previous studies we conclude that HIV encephalopathy does not always give rise to neurological signs.

AIDS Dementia Complex↗
PubMed1990

Fatal encephalitis in a patient with chronic graft-versus-host disease.

A 32-year-old male patient with chronic myelocytic leukemia in accelerated phase received a bone marrow allograft from his 42-year-old HLA/MLC-identical sister. He recovered from acute graft-versus-host disease (GVHD) grade III-IV of skin, liver and gut, but chronic GVHD of progressive onset developed. On day 556 post-graft severe thrombocytopenia was resistant to prednisolone, cyclophosphamide and high dose immunoglobulin. Splenectomy was followed by a normalization of platelet counts. The subsequent clinical course was characterized by progressive muscular atrophy and weight loss. Dysphagia, dysarthria, cachexia and ultimately recurrent pneumonic episodes ensued. The cachectic patient developed a highly abnormal breathing pattern with hypoventilation and intermittent apnea requiring mechanical ventilation. Auditory evoked potentials revealed a considerable dysfunction of the brainstem. The patient died on day 1120 post-graft from pneumonia, aggravated by thoracic muscular insufficiency. Postmortem examination revealed diffuse predominantly lymphoid perivascular infiltration in meninges and CNS tissue; proliferation of activated microglial cells expressing the HLA-DR antigen was prominent in the brainstem. These histologic changes are similar to those observed in the CNS in experimental GVHD. We suggest that this case represents the first documentation of CNS involvement in chronic GVHD.

Adult↗
PubMed1989

[Stereotaxic biopsy of intracranial processes: validity of histologic diagnosis].

The diagnostic validity of stereotactic intracranial biopsies was investigated in 70 patients retrospectively. In 56 cases (80%) the presence of a neoplastic lesion as well as its grade of malignancy was proved by cytological, histological and immunohistochemical techniques. An inflammatory or vascular lesion was found in 8 patients (11.4%). In 6 patients (8.6%) the nature of the lesion remained unclear because of nonspecific histological findings. In 27 cases a correlation was found between the biopsy specimens and corresponding material obtained during open surgery or autopsy. 24 concordant results were found (88.9%). In one case a malignant tumour was classified only according to the findings obtained at operation. In two cases subsequently diagnosed as glioblastoma biopsy reported a higher differentiated astrocytoma and a non-neoplastic lesion, respectively. These results confirm stereotactic biopsy of intracranial lesions as a method with low complication rate and high diagnostic validity.

Astrocytoma↗
PubMed1989

Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease.

The intraneuronal accumulation of paired helical filaments in the form of neurofibrillary tangles is one hallmark of the brain pathology in Alzheimer's disease. At certain predilection sites, a small number of similar lesions are also present in the brains of the majority of aged non-demented individuals. As suggested by several studies before, these abnormal cytoskeletal structures contain determinants of microtubule-associated protein tau and ubiquitin. The present study uses a morphological classification of neurofibrillary tangles into different stages of maturation, as suggested by Alzheimer in 1911, and shows by quantitative immunocytochemistry that early stages of neurofibrillary degeneration contain abnormally phosphorylated tau. Immunoreactivity for the altered tau is seen not only in tangles but also in the cytoplasm of some nerve cells lacking neurofibrillary tangles. Similar numbers of such immunoreactive neurons without tangles are present in age-matched non-demented individuals as in Alzheimer cases, but are absent in young controls. In contrast, incorporation of an epitope, recognized by a monoclonal antibody (3-39) raised to paired helical filaments, which is directed against a determinant residing in the 50-65 amino acid residue region of ubiquitin occurs late in the process of tangle maturation and is most pronounced in extracellular 'ghost tangles'. It is suggested that the accumulation of abnormally phosphorylated tau is one of the earliest cytoskeletal changes in the process of tangle formation. Exposure of certain ubiquitin epitopes in the pathological fibers may reflect an unsuccessful attempt of proteolytic degradation.

Adult↗
PubMed1989

Cytomegalovirus (CMV) disease of the brain in AIDS and connatal infection: a comparative study by histology, immunocytochemistry and in situ DNA hybridization.

Brain tissues from 45 patients with AIDS and two brains with connatal cytomegalic inclusion body disease were investigated for a cytomegalovirus (CMV) etiology of encephalitic lesions. Nineteen brains showed evidence of CMV infection by histology, immunocytochemistry (ICC) using two different antibodies (mono- and polyclonal), and in situ hybridization (ISH). Fourteen cases with typical cytomegalic cells in conventional histology [eight with focally necrotizing encephalitis/ventriculitis including the two connatal infections and six with nodular encephalitis (NE)] revealed CMV with any method. In 5 of 15 AIDS cases of NE without cytomegalic cells, CMV infection was established by ISH, whereas ICC remained negative in these cases. Typical lesions of human immunodeficiency virus (HIV)-induced multi-focal giant cell encephalitis (HIV encephalitis) in 13 brains were never labeled for CMV. In necrotizing encephalitis/ventriculitis, cell types which labeled for CMV, with and without cytomegalic change, comprised neurons, astrocytes, oligodendrocytes, ependyma, choroid plexus, endothelia, and cells in peri- and endoneurium, and in leptomeninges. Both ISH and ICC were able to detect widespread non-cytomegalic CMV-infected cells in normal parenchyma, well beyond the necrotizing lesions, in two AIDS cases. Labeling patterns of nuclei versus cytoplasms varied between the three methods for CMV detection. We conclude that in CNS tissues with cytomegalic cells, ICC and ISH are of comparable sensitivity; however, a diagnosis of CMV disease is possible in such cases by conventional histology. For an in situ diagnosis of CMV infection in NE without cytomegalic cells in AIDS, ISH is the method of choice. A selective vulnerability to CMV infection of any specific cell type of the human CNS is absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Human immunodeficiency virus (HIV)-induced disease of the central nervous system: pathology and implications for pathogenesis.

Significant contributions from many different groups during the last 2 or 3 years have characterized relatively uniform neuropathological changes of the CNS in AIDS patients. They feature human immunodeficiency virus (HIV)-induced multinucleated giant cells as a histopathological hallmark and HIV demonstrable by electron microscopy, immunocytochemistry, and in situ hybridization. Unfortunately, a varying and confusing terminology is used to designate these changes which have been reported in surprisingly different incidences. Focal lesions have a microgranulomatous appearance and were designated as multifocal giant cell encephalitis or subacute encephalitis, which may be confused with the nodular encephalitis caused by cytomegalovirus. For some authors, the latter designation also covers characteristic diffuse white matter changes which have been termed progressive diffuse leukoencephalopathy by others, and which may overlap with focal lesions. Pathological features of these HIV-induced syndromes and other data do not support a major cytopathic effect of HIV on neural cells; rather, they suggest secondary pathogenetic events involving the predominant cell type in the lesion, the monocyte/macrophage/microglia. However, low-level, latent, and persisting HIV infections of neural cells cannot be excluded at present; the CNS may then serve as an early infected virus reservoir. A detailed correlation of clinical symptoms and stage of the infection to neuropathological changes is currently lacking but urgently needed. The presence of the HIV-receptor (CD4) molecule on brain cells is controversial; similarly, a putative cross-reaction of HIV proteins with trophic substances and transmitters needs to be substantiated.

Acquired Immunodeficiency Syndrome↗
PubMed1989

In situ analysis of cell kinetics in human brain tumors. A comparative immunocytochemical study of S phase cells by a new in vitro bromodeoxyuridine-labeling technique, and of proliferating pool cells by monoclonal antibody Ki-67.

A newly developed in vitro labeling method with bromodeoxyuridine (BrdU) identifies S phase cells in situ in freshly obtained surgical tissue of human brain tumors which is subsequently fixed and embedded in paraffin for BrdU immunovisualization. For the first time, the BrdU labeling index (LI) is successfully compared here with the LI obtained by immunostaining of frozen sections of the same tumors with monoclonal antibody Ki-67 which identifies all proliferating cells, i.e., the growth fraction. LIs were counted in at least five different areas with high density of labeled cells; at least 1,000 cells were counted. In 13 metastatic tumors, Ki-67 LI was 8.3%-62.6%, and BrdU LI was 5.1%-28.0%. In 18 gliomas, Ki-67 LI was 1.4%-19.3%, and BrdU LI was 0.2%-11.6%. In 7 meningiomas, Ki-67 LI was 0.3%-3.0%, and BrdU LI was 0%-2.0%. Statistical comparison of Ki-67 and BrdU LIs by linear regression analysis revealed a highly significant correlation: BrdU LI = 0.99 + 0.34 Ki-67 LI (r = 0.92, P less than 0.001). A significant heterogeneity of proliferation patterns may occur within one sample from area to area, as well as between different samples of the same tumor, especially in gliomas; thus, some subjective influence on LIs by arbitrary sampling and selection could occur in quantitative evaluation of in situ cell kinetics of human brain tumors. This study indicates that our in vitro BrdU-labeling method allows the in situ identification of S phase cells in excellently preserved fixed tumor tissue which is well suited for further histological examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1989

Vacuolar myelopathy with multinucleated giant cells in the acquired immune deficiency syndrome (AIDS). Light and electron microscopic distribution of human immunodeficiency virus (HIV) antigens.

Vacuolar myelopathy (VM) is a frequent neurological complication of the acquired immune deficiency syndrome (AIDS). A suspected connection between VM and human immunodeficiency virus (HIV) has been based only on HIV isolation from affected spinal cord tissue. We report here an AIDS patient dying after 14 months of progressive dementia, including 3 months of spinal signs and symptoms. At autopsy, the brain revealed moderate diffuse damage of the white matter compatible with HIV-induced progressive diffuse leukoencephalopathy. The spinal cord showed VM mainly in the lateral and the posterior columns. Mono- and multinucleated macrophages were localized within intramyelinic and periaxonal vacuoles. Light and electron microscopic immunocytochemistry revealed the presence of HIV antigens restricted to mono- and multinucleated macrophages within the spongy lesions. Productive HIV infection is documented for the first time within VM lesions of this case. Therefore, VM should be included among HIV-induced lesions of the central nervous system. The intimate relation of infected macrophages to vacuolar myelinopathy could suggest secretion of a myelinotoxic factor by macrophages productively infected by HIV. Immune electron microscopy appears as promising tool to detect HIV in tissue even when the density of virus may be low.

AIDS Dementia Complex↗
PubMed1989

An antigenic profile of Lewy bodies: immunocytochemical indication for protein phosphorylation and ubiquitination.

An antigenic profile of subcortical and cortical Lewy bodies was determined in the presence or absence of neurofibrillary tangles in the same brain using antisera and monoclonal antibodies to various cytoskeletal elements as well as to determinants not present in the normal cytoskeleton. The cores of many Lewy bodies were strongly reactive with a monoclonal antibody to paired helical filaments which has been shown to recognize ubiquitin. This antibody also stained Marinesco bodies in the same tissue sections. Two monoclonal antibodies to phosphorylated epitopes of neurofilament proteins (SM I 31, SM I 34) stained the peripheries of about 40% of all discernable Lewy bodies on untreated paraffin sections. Reactivity with a monoclonal antibody to neurofilaments (SM I 33) appeared only after pretreatment of the sections with phosphatase. Lewy bodies did not bind antibodies to tau protein. Our results show that, as previously shown for neurofibrillary tangles, Lewy bodies also contain ubiquitin. The uncovering of neurofilament epitopes by treatment with phosphatase indicates that abnormal phosphorylation of cytoskeletal elements may play a role in the pathogenesis of the Lewy body.

Aged↗
PubMed1989

Herpes simplex virus (HSV) DNA in microglial nodular brainstem encephalitis.

Thirty-four brains with microglial nodular brain stem encephalitis were retrospectively investigated for herpes simplex virus (HSV) and cytomegalovirus (CMV) by in situ hybridization (ISH) with biotinylated cDNA probes, and by immunocytochemistry with polyclonal and monoclonal antibodies on formalin fixed paraffin embedded serial tissue sections. In 16 cases (47%), HSV DNA was found by ISH in the nuclei of neurons in microglial nodules or in the adjacent parenchyma of the brainstem, and more rarely at various cerebellar and telencephalic sites. None of the 34 cases was labeled for CMV DNA and none revealed HSV or CMV antigens. Ten control brains without microglial nodules were not labeled. This study suggests an HSV etiology for many cases with microglial nodular brainstem encephalitis.

Brain↗
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

[Immunologic hormone detection in hypophyseal adenomas: correlation of serum hormone findings with immunocytochemical hormone levels in tumor tissue].

Forty-four out of 82 patients with neurosurgically removed pituitary adenomas showed preoperatively elevated plasma hormone levels of prolactin (PRL; 22 patients), of human growth hormone (hGH; 15 patients), and of adrenocorticotropic hormone (ACTH; 7 patients). Immunocytochemical detection of the hypersecreted hormone in paraffin sections of tumour tissue, was possible in all 7 patients (100%) with Cushing's disease, in 20 patients (90%) with hyperprolactinaemia, and in 10 patients (66%) with acromegaly. In a further 3 cases beta-TSH, in one case beta-LH, and in 8 cases alpha-HCG were demonstrated in sections of tumour tissue. No clinical evidence of endocrine disturbance was found in any of these latter cases. More than one anterior pituitary hormone was detected in sections of tumour tissue in 7 cases. An overall qualitative correlation of 85% was found between the elevated plasma hormone level and immunocytochemical hormone detection in tumour tissue sections. Since there is no correlation between conventional histological staining modalities (acidophilic, basophilic, chromophobic) on the one hand, and the level of plasma hormones or immunological hormone detection in tumour tissue on the other hand, modern histological diagnosis of a pituitary adenoma should include assessment of the functional state as found by immunocytochemical hormone determination.

Adenoma↗
PubMed1988

Comparison of in situ DNA hybridization (ISH) and immunocytochemistry for diagnosis of herpes simplex virus (HSV) encephalitis in tissue.

Formol-fixed and paraffin-embedded brain tissue of 33 cases of human necrotizing encephalitis was investigated for Herpes simplex virus (HSV) by immunocytochemistry with a polyclonal antiserum, and by in situ hybridization (ISH) with a biotinylated cDNA probe. HSV antigens (VA) were found in various types of cells in the cytoplasm, cellular processes and nuclei. Labelling by ISH was mostly restricted to nuclei and intranuclear inclusions but otherwise matched the distribution of VA. Eighteen of 25 acute cases had HSV antigen detectable by immunocytochemistry, and 18 of the acute cases contained HSV DNA detectable by our ISH technique. However, results differed somewhat between the techniques: three brains negative for VA showed hybridization, and other 3 VA-positive cases remained negative by ISH. Thus 21 brains with acute necrotizing encephalitis were labelled with one or both techniques. In 8 cases with a subacute course (duration of disease was longer than 1 month), HSV antigens were never detectable although 4 brains showed hybridization. All brains labelled by one or both techniques contained nuclear inclusions bodies. Only one case, of subacute course, with inclusion bodies remained unlabelled. Brain tissue of 11 controls, including cytomegalic inclusion body disease, was never labelled. These results demonstrate that immunocytochemistry and ISH are techniques of comparable sensitivity (72%) for detection of HSV in paraffin sections of acute necrotizing encephalitis brains; their combined use enhanced sensitivity, in our hands, to 84%. In cases with a disease course longer than one month, ISH seems to be the method of choice to demonstrate HSV in situ.

Acute Disease↗
PubMed1987

Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical, and electron microscopical study of 100 autopsy cases.

Neuropathological examination of brain tissue of 100 patients with infection by the human immunodeficiency virus (HIV), including 98 with clinically manifest acquired immune deficiency syndrome (AIDS), revealed distinct multifocal-disseminated and diffuse brain tissue lesions, which can be regarded as HIV-induced brain lesions: multifocal giant cell encephalitis (MGCE; 4) and progressive diffuse leukoencephalopathy (PDL; 25). These lesions were found in 38 brains, and in 17 in absence of infectious, necrotizing or inflammatory changes of other types. In 13 brains, a combination of MGCE with PDL was seen, suggesting a spectrum of HIV-induced brain lesions. MGCE is characterized by perivascular accumulations predominantly of rod cells, monohistiocytes and macrophages, all of which are strongly labeled with a monoclonal antibody to macrophages. Most conspicuous are multinucleated giant cells which are also labeled by anti-macrophage antibody, and which can be regarded as evidence of the local presence of HIV, as confirmed by electron microscopical detection of HIV particles in four MGCE brains, and by immunocytochemical detection of HIV proteins in two MGCE brains. PDL is characterized by a triad: diffuse myelin loss, astroglial proliferation, and infiltration by mono- and multinucleated macrophages. HIV-induced lesions can be morphologically differentiated from histopathological brain lesions known in immunosuppression, including what is called here nodular encephalitis ["subacute encephalitis" of the literature, in most cases attributable to cytomegalovirus (CMV) or toxoplasmosis], by their characteristic histopathology including the hallmark presence of multinucleated giant cells, by direct immunocytochemical and electron microscopical demonstration of HIV in the lesions, and by the absence of opportunistic agents (bacteria, fungi, Toxoplasma, CMV, HSV or papovaviruses). Diffuse poliodystrophy (diffuse proliferation of astroglia with swollen nuclei, occasionally minor neuronal loss and rod cell proliferation) was found in the cerebral cortex and other gray matter in half of all brains, including cases with gyral atrophy, and may be another correlate of HIV damage to the brain. Morphological delineation of HIV-induced brain lesions is a necessary prerequisite for a meaningful clinical definition of HIV-induced cerebral disease.

Acquired Immunodeficiency Syndrome↗