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Biomedical subjects

B Volk

Publications and source records attributed to B Volk.

At least 91 records · Page 5Linked to original sources
PubMed1991

In-vitro matured human macrophages express Alzheimer's beta A4-amyloid precursor protein indicating synthesis in microglial cells.

Microglia which are consistently associated with Alzheimer's disease (AD) senile plaques are part of the mononuclear phagocyte system. In-vitro matured human monocyte-derived macrophages feature many immunological characteristics of microglia. We found strong constitutive expression of Alzheimer's beta A4-amyloid precursor protein (APP) in human mononuclear phagocytes after terminal in-vitro maturation from monocytes to macrophages. Amyloid has previously been found to be associated with microglia in AD brains, however, it remained unclear whether the material was synthesized in or had been phagocytosed by the cells. The findings presented here support the assumption that brain microglia may contribute to APP synthesis in AD brain.

Amyloid beta-Peptides↗
PubMed1991

Alpha 2-macroglobulin synthesis in interleukin-6-stimulated human neuronal (SH-SY5Y neuroblastoma) cells. Potential significance for the processing of Alzheimer beta-amyloid precursor protein.

Cultured human neuronal (SH-SY5Y neuroblastoma) cells synthesize and secrete the potent protease inhibitor alpha 2-macroglobulin (a2M) upon stimulation with interleukin-6 (IL-6) indicating that alpha 2-macroglobulin behaves as an acute-phase protein in the human central nervous system. Exogenous addition of a2M to the cultured neuronal cells resulted in only a slight inhibition of Alzheimer beta A4-amyloid precursor protein (APP) synthesis, but markedly inhibited its secretion pointing to the possibility that a2M may affect the proteolytic APP processing. Evidence is provided that IL-6 and a2M are involved in Alzheimer's disease pathogenesis.

Alzheimer Disease↗
PubMed1991

Gliomatosis cerebri: bioptical approach and neuropathological verification.

Gliomatosis cerebri is rarely encountered and its intra vitam diagnosis has remained difficult. We present biopsy and autopsy findings in three cases that are representative of diffuse glioma, gliomatosis cerebri and diffuse glioblastosis, a modification of the subclassification proposed by Zülch31. Stereotactic biopsy in conjunction with nuclear magnetic resonance tomography (MRT) is recommended as the diagnostic procedure in suspected cases. Immunohistochemical examination with a panel of neuroectodermal markers is helpful in the differential diagnosis but has to take into account that reactive astrocytes may be closely intermingled with the neoplastic glial cells.

Adult↗
PubMed1991

Pancreatic lesions in the von Hippel-Lindau syndrome.

Common manifestations of the von Hippel-Lindau syndrome, an autosomally dominant inherited cancer-prone disorder, include retinal angiomatosis, hemangioblastoma of the central nervous system, renal cysts, renal cancer, pheochromocytoma, and epididymal cystadenoma. Multiple cysts and microcystic (serous) cystadenomas of the pancreas have also been reported occasionally in patients afflicted with this syndrome. In the large Freiburg study of the von Hippel-Lindau syndrome composed of 66 affected individuals, pancreatic lesions were systematically studied. Fifty-five living individuals were examined by abdominal ultrasound imaging. Abnormal findings were confirmed by computed tomographic scan and/or magnetic resonance imaging. For an additional 11 decreased patients autopsy data were available. Cystic lesions of the pancreas were found in 10 patients (15%). One of these patients presented with multiple pancreatic cysts as the only manifestation of the syndrome. In one patient, a malignant islet-cell tumor was found at autopsy. Because multiple pancreatic cysts did not cause major clinical symptoms and because follow-up examinations over an average period of 5 years did not show significant progression of the lesions, it is concluded that these patients usually do not require surgical treatment. Abdominal ultrasound screening is recommended for patients at risk as a tool to identify potential von Hippel-Lindau syndrome gene carriers with pancreatic manifestations. In all patients with multiple pancreatic cysts, the von Hippel-Lindau syndrome should be included in the differential diagnosis.

Adolescent↗
PubMed1991

Mapping of phenytoin-inducible cytochrome P450 immunoreactivity in the mouse central nervous system.

The distribution of phenytoin-inducible cytochrome P450 in non-treated mouse brain and spinal cord was analysed immunohistochemically using polyclonal antibodies against phenytoin-induced mouse cerebral microsomal P450. This P450 protein was proved in Ouchterlony [Volk B. et al. (1988) Neurosci. Lett. 84, 219-224], Western blot, and immunohistochemical analyses to be reactive to the specific antibodies and an IgG fraction raised against phenobarbital-induced rat liver microsomal P450IIB1. The phenytoin-induced P450 is designated P450IIB1* because immunologically it is comparable with P450IIB1; however, it has not yet been analysed for other characteristics of this enzyme. Immunocytochemistry was performed on acetone-fixed serial cryosections of the whole brain using the avidin-biotin-peroxidase detection system. Negative controls included incubations with preimmune serum of the immunized animal instead of the primary antibody and preabsorption of the antibody with the corresponding immunogen. The pattern of immunoreactive sites indicates that P450IIB1* is not distributed evenly throughout the CNS. It was found to be restricted to only some cellular populations. The most striking aspect of immunostaining was a predominant reactivity in the evolutionary old brain parts. Neuropil and neuronal staining was found in the spinal cord (motor neurons of the ventral horn), medulla oblongata (hypoglossal nuclei, magnocellular part of the lateral reticular nuclei), pons (trigeminal, facial, cochlear and pontine nuclei), cerebellum (granule cells), midbrain (dorsal raphe nucleus) and limbic lobe (hippocampal pyramidal cells). Neuropil reactivity alone appeared in cerebellar nuclei, midbrain, thalamus, basal ganglia, neopallium and olfactory brain. Generally, pia mater/arachnoid, ependyma, choroid plexus, vascular system and some astrocytic populations were found to be strongly P450IIB1* immunoreactive. In comparison with astroglia, which is characterized by glial fibrillary acidic protein-positiveness, the astrocytes, which are also P450IIB1* reactive, occurred only in subpial and subependymal layers, and in large fiber tracts of the spinal cord and brainstem, where they were attached to the vascular system. Otherwise, the glial fibrillary acidic protein-positive astrocytes were not P450IIB1* immunoreactive in the cerebellar molecular layer (fibers of Bergmann glia), in remaining neuropils and in white matter areas.

Animals↗
PubMed1989

Cerebellar injury due to phenytoin. Identification and evolution of Purkinje cell axonal swellings in deep cerebellar nuclei of mice.

The present study describes the identification and the ultrastructural and numerical evolution of Purkinje cell axonal swellings induced by phenytoin. Thirty male C57Bl/6J mice received phenytoin orally in doses up to 100 mg/kg daily and were killed after 3, 6, 10, 14, and 48 days of treatment. Light and electron microscopic investigations as well as morphometric analysis of cut surface area and numerical density of axonal swellings were performed. The swellings appeared as early as 6 days after initiation of treatment and gradually increased in size and frequency. Use of an anti-lymphocyte monoclonal antibody (CD 3), specifically cross-reacting with Purkinje cells, identified the swellings as dystrophic Purkinje cell axons. On grounds of their ultrastructural appearance they were classified into three distinct types occurring at different time intervals after phenytoin exposure. At 6 days, most axonal swellings contained loosely aggregated membranous vesicles and tubules in a finely granulated matrix (type 1). At 14 days, larger axonal swellings appeared characterized by the presence of three-dimensional networks of branched and anastomosing membranous tubules (type 2). At 48 days, even larger axons contained bodies of highly condensed membranous material of sometimes paracrystalline appearance (type 3). It is suggested that phenytoin-induced axonal pathology of Purkinje cells is a dynamic process characterized by the progressive accumulation of proliferating membranous material arranged in an increasingly complex fashion.

Animals↗
PubMed1989

Disseminated human neurocysticercosis. A morphologic analysis of two cases.

This study was based on two cases of disseminated human neurocysticercosis from India. The material available was examined grossly, and by light microscopy, histochemistry, immunomorphology and electron microscopy. The results showed that the parasites commonly embolized to the anatomically discernable gray-white matter junction of the brain and were located in cavities, the walls of which were dilated vascular channels. The parasite-nutrition process was through endocytosis and microtrichal activity. To camouflage themselves from the host-defense mechanisms, the parasites apparently covered themselves with host-tissue-like material. Host reactivity to the parasite was heralded morphologically by the physical anchoring of the parasite by activated endothelial cells, loss of the host-tissue-like cover and an acute polymorphonuclear leucocytic response.

Brain Diseases↗
PubMed1989

Cell loss in the cerebellum and hippocampal formation of adult rats after long-term low-protein diet.

Whereas quite a number of previous reports have shown that the developing brain is vulnerable to protein deprivation, the mature CNS is usually considered resistant to this condition. To explore this assumption the present experimental model was built on groups of 2-month-old rats fed with a low-protein diet (8% casein) for 6, 12, and 18 months and respective age-matched controls fed for the same periods with a standard laboratory chow (27% casein). The numerical density of cerebellar granule cells was estimated using three different stereological procedures (classical, unfolding, and disector). By all methods a significant cell loss was demonstrated. In the hippocampal region the numerical densities of dentate gyrus granule cells and the CA3 pyramidal cells were estimated using the unbiased disector method. A significative and progressive loss of neurons was likewise found. The occurrence of cell loss after lengthy periods of undernutrition in adulthood is thus an issue of paramount importance if extrapolation can be made to the human brain.

Animals↗
PubMed1989

[KI-67 PAP stain for histologic grading of brain tumors by squash preparations].

Using Ki-67 monoclonal antibody to the nuclear antigen of proliferating cells, the squash preparations of 141 brain tumors and the 36 frozen sections from corresponding tumor tissues were stained with peroxidase-antiperoxidase method. The staining indices in squash preparations correlated well to those in the corresponding frozen sections. There were good correlations between the percentage of stained cells and the histologic grade in agreement with known biologic behavior. In order of decreasing malignancy, the averages of Ki-67 staining indices were 26.7% for metastatic carcinomas, 12.6% for glioblastomas, and less than 2.8% for benign mesodermal tumor groups. Ki-67 staining with squash preparations could be applied to small tissues obtained by transsphenoidal surgery and stereotactic surgery as valuable adjuncts to intraoperative histologic diagnosis and the estimation of histologic malignancy.

Adenoma↗
PubMed1989

[The significance of stereotaxic brain biopsy in atypical multiple sclerosis].

Multiple sclerosis (MS) is one of the most common diseases of the central nervous system. Up to now, there is no pathognomonic test to ascertain the diagnosis and in 10 to 15% of MS cases there are problems in differential diagnosis. We report 15 bioptically diagnosed MS cases with atypical clinical, C.S.F. and neuroradiological findings. In each case the diagnosis of MS was made by CT/MRI-stereotactic brain biopsy. Neoplastic and other non-tumorous lesions could be excluded. Indications for and significance of stereotactic brain biopsy in atypical cases of MS are discussed.

Adult↗
PubMed1989

Blood-derived phagocytes in the cerebellar cortex of the rat after chronic alcohol consumption.

Past work showed that chronic alcohol consumption induces massive degeneration in the rat cerebellar cortex. To study the subsequent process of nervous tissue repair, followed itself by a remodelling activity, groups of alcohol-treated rats for 3 and 6 months were used and the results compared with the respective age-matched controls. From the wide variety of cells which display phagocytic activity in the mammalian brain it was found, based on qualitative observations, that two types were clearly involved in the removal of the alcohol-induced degenerated debris: the resident microglial cells and the non-resident brain macrophages. This assumption was corroborated by the study of their origin, using carbon particles and latex beeds intravenously injected, which showed that brain macrophages were the sole population to be labelled. These observations fit with the multiple origin concept for neural phagocytosis which postulates that different cell types can be recruited for the removal of the damaged neural tissue depending on the severity of the lesions and on the extension of the blood vessels damage.

Alcoholism↗
PubMed1988

First evidence of cytochrome P-450 induction in the mouse brain by phenytoin.

Long-term administration of phenytoin (60 mg/kg) to male C57Bl/6J mice causes an average drug serum level of 16-19 micrograms/ml. Cytological changes consisting of focal axonal swellings in the deep cerebellar nuclei are characterized by an increasing accumulation of vesiculotubular membranes in the dense, but ribosome-deficient axoplasm. Microsomal fractions of brain and liver were prepared at intervals until the 80th day of treatment to determine their cytochrome P-450 activities and isoenzyme characteristics. The cerebellar tissue was shown to be distinguished by a 15-fold enhancement of cytochrome P-450 PB3a activity, that means twice the extent of that found in liver and cerebrum.

Animals↗
PubMed1988

An extended HLA-D region haplotype associated with celiac disease.

Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. We previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II beta-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. We now report the isolation of this beta-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP beta chain. This celiac disease-associated HLA-DP beta-chain gene was flanked by HLA-DP alpha-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP alpha-chain genes of celiac disease patients also were studied by RFLP analysis; 84% of HLA-DR3, -DQw2 patients had a 16-kb Xba I fragment that was present in only 36% of HLA-DR3, -DQw2 controls. Moreover, 79% of these patients had both alpha- and beta-chain polymorphisms in contrast to 27% of controls. Thus, celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP alpha- and beta-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion.

B-Lymphocytes↗