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Biomedical subjects

B Volk

Publications and source records attributed to B Volk.

At least 73 records · Page 4Linked to original sources
PubMed1994

Increased levels of nerve growth factor (NGF) protein and mRNA and reactive gliosis following kainic acid injection into the rat striatum.

After excitotoxic lesion of the rat striatum, the time courses of local nerve growth factor (NGF) and NGF mRNA contents were investigated using a sensitive immunoassay (ELISA) and reverse transcription coupled to polymerase chain reaction (RT/PCR). To investigate a possible correlation of increased NGF expression and excitotoxin-induced reactive gliosis, striata were also analysed by immunohistochemistry with glial markers. We found elevated striatal NGF protein after lesion over the whole observation period. NGF mRNA showed a biphasic increase 10 h and 10 days after lesion, the latter co-inciding with an increased astrogliosis. These results indicate that NGF accumulation after excitotoxin-induced neurodegeneration is partly due to local reactive astrocytes.

Animals↗
PubMed1994

Long-term effects of intermittent versus continuous ethanol exposure on hippocampal synapses of the rat.

The hippocampus is known to be very sensitive to a large spectrum of different neurotoxins including ethanol. Ethanol administered continuously or intermittently may affect the hippocampus in different ways. Intermittent administration of ethanol has many features in common with the low level electrical stimulation protocols which lead to the functional changes associated with the phenomenon of kindling. In this study, the differential effects of intermittent intraperitoneal ethanol injections (3 g/kg twice daily) and continuously administered ethanol in drinking water (20%) on hippocampal synapses in the rat were studied using ethanolic phosphotungstic acid staining and electron microscopy. After 1 month of intermittent exposure a significant reduction (18%) of synapses was seen in the stratum lucidum of the CA3 region. Continuously treated animals showed no significant change over this time despite a higher total ethanol intake. In the dentate gyrus, a compensatory increase in supragranular synaptic number was seen only in continuously treated animals. These findings demonstrate the sensitivity of synapses of the hippocampus to the presence of ethanol and the larger effects of peaking ethanol concentrations compared to more constant levels. These results emphasize the need to consider the differential effects of various types of ethanol consumption also on the human brain.

Animals↗
PubMed1994

Interstitial 125-iodine radiosurgery of low-grade gliomas of the insula of Reil.

Between 1979 and 1991 67 patients with low-grade gliomas of the insula (of Reil) were treated with 125-iodine interstitial radiosurgery. Retrospective analysis with a median follow-up of 55 months demonstrated a 5- and 10-year survival rate of 54% and 47%, respectively, for all low-grade gliomas treated and a 5- and 10-year survival rate of 57% for 49 patients with astrocytomas WHO grade II analysed separately. The median Karnofsky performance status of survivors was 90%. Malignant change was the cause of death in 85%, failure to control tumour growth in the remaining cases. Multivariate analysis with a Cox proportional hazard model identified solely the pre-operative Karnofsky performance score of 70-80 vs. 90% as a prognostic factor for outcome (p = 0.001, risk ratio 3.62), but not age, gender, tumour volume, length of disease before treatment, mode of implantation, or major vs. moderate or no shrinkage of tumour volume after interstitial radiosurgery. Thus, 125-iodine radiosurgery yielded survival rates in these deep-seated insular gliomas comparable to those reported after surgery and radiation therapy of lobar tumours. This was achieved with a low peri-operative mortality and morbidity and at low costs.

Adolescent↗
PubMed1994

Polymorphous high-grade B cell lymphoma is the predominant type of spontaneous primary cerebral malignant lymphomas. Histological and immunomorphological evaluation of computed tomography-guided stereotactic brain biopsies.

In this retrospective study, a series of 54 patients (1982-1989) with sporadic primary cerebral malignant lymphomas is presented. All diagnoses were uniformly done on computed tomography-guided stereotactic brain biopsies according to histological criteria and immunomorphological data. In this series, the tumors were predominantly (25 of 48; 52%) classified as polymorphous high-grade blastic B cell lymphomas. This lymphoma type is therefore regarded as the most common type of sporadic primary cerebral non-Hodgkin's lymphoma. Severe regression (++/ ), which may dramatically alter the morphological appearance of a brain lymphoma, was found in 24 of 28 (86%) of cases with glucocorticoid administration prior to stereotactic brain biopsy.

Adolescent↗
PubMed1994

[A case of paraneoplastic limbic encephalitis in autoptic occult primary malignancy].

We report a case of limbic encephalitis in a 71-year-old male who presented with amnesia, confusion and disorientation. The patient's history of long standing alcoholism suggested the diagnosis of Korsakow syndrome. Autopsy, however, revealed a regional lymph-node metastasis of a small-cell bronchial carcinoma. No primary malignoma could be detected. These findings indicate that in cases of limbic encephalitis without detectable primary malignoma a paraneoplastic syndrome cannot be excluded. This has to be taken into consideration when discussing the etiology of limbic encephalitis (paraneoplastic versus virus-induced).

Aged↗
PubMed1994

Kainate receptor gene expression in the developing rat brain.

Kainate-preferring receptors are a subclass of ionotropic glutamate receptors that might play a role in brain development. The expression of the five known genes encoding kainate receptor subunits (GluR-5, -6, -7, KA-1, and KA-2) was studied by in situ hybridization during pre- and postnatal development of the rat brain. We compared the combined expression patterns of these genes with autoradiography using 3H-kainate in the developing brain from embryonic day 12 (E12) through to adult. Although mRNAs for the receptor subunits (except KA-1) can be detected at stage E12, 3H-kainic acid binding (as an index of receptor protein) is not found at this stage. However, by E14 high-affinity kainate sites are found throughout the gray matter, but particularly in spinal cord, primordial cerebellum, and ventral forebrain structures. All genes undergo a peak in their expression in the late embryonic/early postnatal period. GluR-5 expression during development shows the most interesting features because the changes are qualitative. The GluR-5 gene shows peaks of expression around the period of birth in the sensory cortex (layers II, III, and IV), in CA1 hippocampal interneurons in the stratum oriens, in the septum, and in the thalamus. GluR-6 shows a prenatal expression peak in the cingulate gyrus of the neocortex. KA-1 transcripts appear with the development of the hippocampus and remain largely confined to discrete areas such as the CA3 region, the dentate gyrus, and subiculum. KA-2 transcripts are found throughout the CNS from as early as E12 and remain constant until adulthood. The GluR-5 and GluR-6 genes are coexpressed in multiple peripheral ganglia (e.g., cranial nerve ganglia, dorsal root ganglia, and mural ganglia) at E14.

Aging↗
PubMed1993

Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease.

BACKGROUND: Pheochromocytoma is a feature of two disorders with an autosomal dominant pattern of inheritance--multiple endocrine neoplasia type 2 (MEN-2) (with medullary thyroid carcinoma and hyperparathyroidism) and von Hippel-Lindau disease (with angioma of the retina, hemangioblastoma of the central nervous system, renal-cell carcinoma, pancreatic cysts, and epididymal cystadenoma). The frequency of these syndromes in patients with pheochromocytoma is not known. METHODS: In an unselected group of patients with pheochromocytoma, we performed pentagastrin tests, parathyroid hormone assays, computed tomography (CT) or magnetic resonance imaging (MRI) of the brain, ophthalmoscopy, CT imaging of the abdomen, and ultrasonography of the testes. We also screened members of families with MEN-2 or von Hippel-Lindau disease for pheochromocytoma by measuring plasma and urine catecholamines and plasma chromogranin A and by performing abdominal ultrasonography, CT and MRI, and metaiodobenzylguanidine scintigraphy. RESULTS: Nineteen of 82 unselected patients with pheochromocytomas (23 percent) were carriers of familial disorders; 19 percent had von Hippel-Lindau disease and 4 percent had MEN-2. Prospectively, in 36 of 79 subjects at risk for pheochromocytoma (46 percent), 42 unsuspected pheochromocytomas were found. Overall, there were 130 patients with 185 pheochromocytomas; 43 had von Hippel-Lindau disease, 24 had MEN-2, and 63 had sporadic tumors. The patients with familial and those with sporadic pheochromocytomas differed in mean age at diagnosis (32 vs. 46 years, P < 0.001), multifocal localization (55 vs. 8 percent, P < 0.001), and cancer (0 vs. 11 percent, P = 0.005); but not in the frequency of extraadrenal tumors (24 vs. 16 percent). Thirty-eight percent of carriers of von Hippel-Lindau disease and 24 percent of carriers of MEN-2 had pheochromocytoma as the only manifestation of their syndrome. CONCLUSIONS: All patients with pheochromocytomas should be screened for MEN-2 and von Hippel-Lindau disease to avert further morbidity and mortality in the patients and their families. All patients in families with MEN-2 or von Hippel-Lindau disease should be screened for pheochromocytoma, even if they are asymptomatic.

Adolescent↗
PubMed1993

Intrastriatal cerebellar grafts: differentiation of cerebellar anlage and sprouting of Purkinje cell axons.

Pieces of cerebellar primordia were obtained from G16 (day 16 of gestation) rat fetuses and stereotaxically injected into the striatum of adult Wistar rats. The transplants were allowed to integrate with the host brain for 2 h up to 6 months after implantation. Ninety four out of 105 transplants perfectly integrated with the host brain (90%) and established the typical trilaminar histoarchitecture of cerebellar cortex. The transplants were sufficiently vascularized. Vessels seen within the grafts provided all ultrastructural elements of a blood-brain barrier. Light microscopic evaluation of graft development showed no considerable retardation of cerebellar histogenesis. Electron microscopic examination disclosed normal ultrastructure of cerebellar neurons, as well as elements of regular synaptic organization. The topic of efferent graft-to-host projections was investigated 2.5 months after transplantation using the monoclonal Purkinje cell marker anti-Leu-4 (CD3). This method allowed us to detect immunoreactive, morphologically intact axons of grafted Purkinje cells running over long distances (at least 500 microns) within the host striatum. Whilst afferent but in no case efferent connections of heterotopic cerebellar transplants had been demonstrated elsewhere, we could now prove the reciprocal modus of graft-host interaction with heterotopic cerebellar grafts.

Animals↗
PubMed1993

Influence of phenytoin on cytoskeletal organization and cell viability of immortalized mouse hippocampal neurons.

Phenytoin (PHT) is a commonly used anticonvulsant drug; several side effects have been described, including morphological changes in brain cortex and cerebellar neurons and teratogenic lesions in infants of epileptic mothers. Evidence of other authors indicate that PHT may exert its action through the modification of phosphorylation patterns of cytoskeletal polypeptides. We have studied the influence of the anticonvulsant drug phenytoin on immortalized mouse hippocampal neurons in culture. This was done by means of MTT-assays, immunocytochemical and immunoblot analyses, measurements of cell metabolism, measurements of the length of neuronal processes, and electron microscopy. A distinct and pronounced effect of PHT could be characterized with regard to the formation of neuronal processes, involving malfunction of an assembly-mechanism of cytoskeletal constituents. These accumulated within appendages (blebs) or cytoplasmic condensations, instead of forming normally organized processes. However, PHT did not interfere with bulk synthesis of cell proteins and specific cytoskeletal components.

Animals↗
PubMed1993

Effects of perinatal hypo- and hyperthyroidism on the levels of nerve growth factor and its low-affinity receptor in cerebellum.

Deficits or excesses of thyroid hormones during critical periods of mammalian cerebellar development can lead to profound biochemical and morphological abnormalities in this system. The goal of this study was to investigate the effects of perinatal hypo- and hyperthyroidism on the ontogeny of nerve growth factor (NGF) and its low-affinity receptor (p75NGFR) in the rat cerebellum. The concentration of NGF and of p75NGFR immunoreactivity (IR) were measured, several days after birth, in cerebella of rats which had received propylthiouracil (PTU) or thyroxine. NGF concentration was markedly enhanced only on postnatal day 2 (P2) in hyperthyroid rats, whereas in hypothyroid (PTU-treated) rats NGF values were similar to age-matched controls. These observations suggest that thyroid hormone affects NGF synthesis during early periods of cerebellar development. In Purkinje cells of control animals, p75NGFR IR peaked at P10. In hypothyroid rats, the expression of p75NGFR was retarded, peaking at P15, whereas in hyperthyroid rats it was advanced, peaking at P8. The increased p75NGFR IR found in Purkinje cell bodies and the delayed disappearance of p75NGFR IR from the external granular layer of hypothyroid rats suggest different roles for thyroid hormone in the developing cerebellum. We conclude that p75NGFR and NGF are independently regulated by thyroid hormone during critical periods of cerebellar development. The effect of thyroid hormone deficiency on p75NGFR content in Purkinje cells may involve complex mechanisms such as impaired efficiency of axonal transport.

Animals↗
PubMed1993

Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor.

Since immunohistochemical studies indicated the presence of interleukin-6 in the cortices of patients with Alzheimer's disease, we were interested in the eventual biological effects of this cytokine on neuronal cells. We found that interleukin-6 and interleukin-1 induced metallothionein expression in a human neuronal (SH-SY5Y neuroblastoma) cell line. In contrast to metallothionein, amyloid precursor protein expression was unaffected by both cytokines. When searching in the same cell line for the expression of the classical 80-kDa interleukin-6 binding protein, which is part of the dimeric interleukin-6 receptor, we were unable to detect the respective mRNA. Our findings either indicate that the interleukin-6 receptor in these cells is expressed in extremely low levels or that interleukin-6 may act upon neuronal cells via a different, yet unknown neuronal receptor.

Amyloid beta-Protein Precursor↗
PubMed1993

Cytoplasmic expression of the leu-4 (CD3) antigen in developing Purkinje cells in the rat cerebellum.

Although commonly known to represent a T cell receptor (CD3) associated polypeptide, the leu-4 (CD3) antigen occurs in cerebellar Purkinje cells (PCs) of many species. The monoclonal pan T lymphocyte marker anti-leu-4 (CD3) recognizes both the lymphocytic and the Purkinje cell type of this antigen [22]. To obtain more information about the merit of anti-leu-4 (CD3) as an investigational tool, we evaluated the expression of leu-4 (CD3) in PCs of the developing rat cerebellum (in situ) by light microscopy. Positive anti-leu-4 (CD3) immunoreaction of PCs did not occur prior to post-natal day (D) 4. The analysis of immunostaining during cell differentiation revealed three major phases of post-natal PC maturation including antigenic development of cell somata (phase 1: until D6), dendrites (phase 2: D7-D11), and axons (phase 3: D12-D14). A massive post-weaning expansion of the dendritic arborization led then to the mature PC architecture. Additionally, the leu-4 (CD3) antigen was observed in ectopic PC dendrites (D10) and in ectopic (mature) PCs. Throughout post-natal development as well as in mature PCs, the leu-4 (CD3) antigen was found to be cytoplasmic. Due to its labile nature, neither an ultrastructural localization nor molecular characterization could be achieved. For the same reason, its application is basically restricted to cryo-fixed cerebellar tissue. However, at the level of light microscopy, the monoclonal human T cell marker anti-leu-4 (CD3) proved to be a useful tool for specific and sensitive labelling of differentiated cerebellar PCs in the rat.

Aging↗
PubMed1992

CT and MRI: prognostic tools in patients with AIDS and neurological deficits.

To determine the prognostic value of CT and MRI in AIDS we studied the survival of patients with neurological involvement, in relation to the initial imaging results. Twenty-six initial CT and 15 MRI examinations of 41 patients were reviewed for the presence of cerebral atrophy and/or focal lesions. The mean survival time of patients with initially normal imaging was longer (700 +/- 89 days) than that of patients with isolated cerebral atrophy (326 +/- 65) or isolated focal lesions (202 +/- 97). The shortest survival (78 +/- 44 days) was found in patients with both cerebral atrophy and focal lesions. The risk of death in patients with atrophy alone was 3.6 times higher, that in patients with focal lesions alone 6.4 times higher, and in patients with both changes 19.3 times higher than in patients with initially normal imaging. Cerebral imaging with CT and/or MRI thus allows identification of AIDS-related cerebral changes and may contribute to assessment of prognosis.

AIDS Dementia Complex↗
PubMed1992

Primary cerebral malignant non-Hodgkin's lymphomas: a retrospective clinical study.

In this retrospective study a series of 54 patients (seen from 1982 to 1989) with sporadic primary cerebral malignant lymphomas (PCML), which were uniformly classified with the support of immunocytochemical data, is presented. The analysis shows that on CT PCML are shown as cirumscribed, homogeneous, contrast-enhanced multifocal (70%) or solitary (30%) mass lesions within the subcortical white matter; they were found mainly close to the ventricular system or the subarachnoid space. To prove the histological diagnosis and for the purposes of differential diagnosis, low-risk CT-stereotactic biopsy is necessary and is the method of choice. Immunomorphological techniques are valuable adjuncts to confirm the histological diagnosis of PCML. In the series presented these tumours have been predominantly classified as high-grade blastic B-cell lymphomas. For this reason, this type should be regarded as the prevalent variant of malignant brain lymphomas. The evaluation of possible prognostic factors suggests that age at admission and morphological features of regression are relevant determinants of survival time. A correlation between neuroradiological evidence of a decrease in tumour size, morphological signs of regression and glucocorticoid administration has been found. Thus, patients suspected of having PCML require rapid diagnosis prior to corticosteroid administration. PCML have been shown to be radioresponsive, but not curable. Because of the lack of uniformity in management of this rate brain neoplasm, the different treatment protocols are not comparable, and hence the optimum therapy has not been satisfactorily determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1992

Central nervous system lesions in von Hippel-Lindau syndrome.

CNS manifestations were studied in 97 gene carriers of von Hippel-Lindau syndrome (HLS). Haemangioblastomas of the CNS were found in 43 patients (44%), 23 females and 20 males. The mean age at diagnosis was 39 years (12-73 years). A total of 93 haemangioblastomas were detected of which 74% were intracranial and 26% were located in the spinal cord; 75% were predominantly cystic and 25% presented as solid lesions. Multiple lesions were found in 42% of HLS-associated haemangioblastomas, but in none of 51 patients with CNS haemangioblastoma without HLS. Haemangioblastoma was the cause of death in 82% of patients with HLS. Although microsurgery has considerably improved post-operative results, multifocal tumour development and recurrence remain a serious problem in the clinical management of HLS gene carriers.

Adolescent↗
PubMed1992

Detection of interleukin-6 and alpha 2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer's disease patients.

We examined brains from Alzheimer's disease (AD) patients by immunohistochemistry for the presence of protease inhibitors. Immunoreactivity for alpha 2-macroglobulin (alpha 2-M), the most potent of the known human protease inhibitors, was found in a subgroup of cortical and hippocampal AD senile plaques. In addition, large hippocampal neurons in AD brains displayed intracellular alpha 2-M immunoreactivity which was consistently stronger than in normal aged brains. In cultured human cells of neurogenic origin (SH-SY5Y neuroblastoma cells), alpha 2-M synthesis could be strongly induced by the inflammatory cytokine interleukin-6 (IL-6) indicating that human alpha 2-M behaves as an acute-phase protein in the nervous system. Therefore, we also examined AD brains for the presence of IL-6 and found strong immunostaining in and around a subgroup of senile plaques as well as around large cortical neurons. Only very few senile plaques also stained for C-reactive protein, an acute phase protein known to be inducible by IL-6. We propose that the presence of IL-6 and alpha 2-M immunoreactivity in AD brains is functionally linked and that a sequence of immunological events is part of the pathology of AD.

Aged↗
PubMed1991

A clinicopathologic and immunomorphologic study of 13 cases of ganglioglioma.

The authors present the clinical, histopathologic, and immunomorphologic data of 13 intracranial gangliogliomas. Preoperative computed tomography scans showed a commonly cystic tumor of variable density. Six tumors were completely excised and seven were subtotally resected. After a mean follow-up of 4.5 +/- 2.6 years, 11 patients are asymptomatic or only slightly incapacitated. All tumors were examined with a panel of neuronal and neuroendocrine markers. Immunoreactivity (IR) to anti-neurofilament polypeptide (clone 2F11) was observed in neuronal processes in ten cases and in neuronal perikarya in five. With anti-synaptophysin (clone SY38), IR was present along the lining of ganglion cell perikarya and processes in 11 tumors whereas staining of the perinuclear cytoplasm was prominent in two. IR to anti-chromogranin A (clone LK2H10) was observed within the neuronal perikarya in eight cases. Only one ganglioglioma of the brain stem showed IR for tyrosine-hydroxylase (clone 2/40/15) and dopamine-beta-hydroxylase in some neoplastic ganglion cells. In this study, synaptophysin was the most reliable neuronal marker. For immunocytochemical identification of neoplastic neurons in ganglioglioma as well as other tumors with neuronal differentiation the authors propose a panel of well-characterized monoclonal antibodies against neurofilament polypeptides, synaptophysin, and chromogranin A to support the histomorphologic diagnoses.

Adolescent↗