Biomedical subjects

B Volk

Publications and source records attributed to B Volk.

At least 55 records · Page 3Linked to original sources

PubMed1996

Occurrence of interleukin-6 in cortical plaques of Alzheimer's disease patients may precede transformation of diffuse into neuritic plaques.

Interleukin-6 (IL-6) immunoreactivity has previously been shown in plaques in Alzheimer's disease (AD), and elevated IL-6 concentrations have been measured biochemically in brains of AD patients. In this report, we present data on the appearance of IL-6 immunoreactivity in AD plaques according to the stage of plaque formation. Diffuse plaques are found in the early stages of plaque formation, whereas primitive and classic plaques are thought to represent later stages of plaque pathology. We classified plaques using the Bielschowsky silver stain method in serial sections of paraffin-embedded cortices of clinically diagnosed and histopathologically confirmed AD patients and patients with no clinical history of dementia. In the brains of nondemented and demented persons, we found plaques using the silver staining method or immunohistochemistry with antibodies against the amyloid precursor protein. In the nondemented group, diffuse plaques were the predominant plaque type, whereas primitive plaques formed the larger proportion of lesions in the group of AD brains. IL-6 was only detectable in plaques of demented patients. In AD cases, IL-6 was found in a significantly higher ratio in diffuse plaques as would have been expected from a random distribution of IL-6 in all plaque types. We conclude that the presence of IL-6 immunoreactivity correlates with clinically detectable dementia. In addition to the ubiquitous presence of amyloid in nondemented and demented brains, an IL-6-related immunological mechanism may be involved both in the transformation from diffuse to primitive plaques in AD and in the development of dementia.

Aged↗

PubMed1996

Bilateral myoclonus of the trapezius muscles after distal lesion of an accessory nerve.

Observations of rhythmic or semirhythmic myoclonus due to a peripheral nerve lesion are exceptional. We report on a patient with thorax trauma with multiple bilateral hematomas of the paravertebral musculature. Eight years later he developed rhythmic myoclonus of both trapezius muscles and thoracic pain. Infiltration of a paramedially located scar at the level of D5-6 with a local anesthetic agent led to an intermittent relief of the myoclonus as did anesthetic blockade of the left accessory nerve. Surgical excision of the scar, which contained multiple dystrophic axons on histological examination, cured the patient's symptoms as illustrated in a videotape. This indicates that peripheral afferents contributed to the myoclonus. Ephaptic transmission, ectopic excitation, or misdirected neuronal sprouting secondary to the trauma are possible peripheral mechanisms responsible for the movement disorder. Successful blockade of the left accessory nerve with bilateral relief of the symptoms suggests a secondary, more centrally located mechanism, e.g., in the brain stem, probably driven by an altered afferent input. It is concluded that rhythmic or semirhythmic and focal myoclonus need a careful workup to look for a peripheral cause because such a condition would be accessible for surgical treatment.

Accessory Nerve↗

PubMed1996

Central pontine myelinolysis: clinical presentation and radiologic findings.

Central pontine myelinolysis (CPM) is a neurologic disorder once thought to be uniformly fatal. With the introduction of CT and MRI there was an increasing number of reports on nonfatal cases of CPM. Nearly all reports on nonfatal cases describe severe clinical syndromes with tetraparesis, bulbar palsy, and coma. We reviewed nine patients with CPM and compared the size of the pontine lesion on MRI and CT with the severity of clinical presentation. Clinical presentation of CPM was highly variable: The symptoms ranged from severe neurologic disorders to mild neurologic disturbances only. Two of nine patients died from CPM. The size of the pontine lesion did not correlate with the severity of the neurologic illness or the final outcome. Mild forms of CPM might be difficult to diagnose clinically. This applies even more for patients with underlying diseases such as Wernicke's encephalopathy, which in itself might cause a clinical picture similar to that of CPM. Central Pontine Myelinolysis is a major differential diagnosis in acute neurologic deterioration indicating pontine damage. Magnetic resonance imaging is the decisive diagnostic tool for CPM.

Adult↗

PubMed1996

Inflammatory mechanisms in Alzheimer's disease.

In recent years many studies have indicated an involvement of inflammatory mechanisms in Alzheimer's disease (AD). Acute-phase proteins such as alpha 1-antichymotrypsin and c-reactive protein, elements of the complement system, and activated microglial and astroglial cells are consistently found in brains of AD patients. Most importantly, also cytokines such as interleukin-6 (IL-6) have been detected in the cortices of AD patients, indicating a local activation of components of the unspecific inflammatory system. Up to now it has remained unclear whether inflammatory mechanisms represent a primary event or only an unspecific reaction to brain tissue damage. Therefore, we investigated whether IL-6 immunoreactivity could be found in plaques prior to the onset of neuritic changes, or whether the presence of this cytokine is restricted to later stages of plaque pathology. We confirmed our previous observation that IL-6 is detectable in a significant proportion of plaques in the brains of demented patients. In AD patients IL-6 was found in diffuse plaques in a significant higher ratio as would have been expected from a random distribution of IL-6 among all plaque types. This observation suggests that IL-6 may precede neuritic changes, and that immunological mechanism may be involved both in the transformation from diffuse to neuritic plaques in AD and in the development of dementia.

Alzheimer Disease↗

PubMed1996

Large, virus-like sinuous tubules in the endoplasmic reticulum of human neurons: report from a case of encephalopathy and brief critical review.

We report a case of a rapidly progressive, fatal non-inflammatory demyelinating disease, distinct from multiple sclerosis and lysosomal disorders, in a patient with progressive dementia. Electron microscopy of stereotactic brain biopsy samples revealed the presence in neurons of sinuous, double-walled cylindrical membranous structures within the cisterns of the endoplasmic reticulum. These structures were 75-80 nm in overall diameter, up to 1.5 mm long and had a 40- to 45-nm diameter core. The possibility that they might be viruses of the Filoviridae or Paramyxoviridae families was considered, but the inclusions differed in key morphological aspects from members of both virus families and there were no supporting clinical or pathological data. Neither was it possible to assign the structures to any other known virus family on the basis of their morphology. Such inclusions have been the subject of only three published reports over the past 20 years. Evidence suggests that they may be confined to human central nervous system neurons, but occur in unrelated disorders (Alzheimer's disease, amyotrophic lateral sclerosis, meningoencephalitis, low-pressure hydrocephalus, demyelination). The possibility that they are formed in certain neurons by an abnormal internal budding process, as a response to a variety of pathological insults, is considered most likely, although an infectious origin (such as an unrecognised virus with variable clinical effect) cannot be ruled out.

Adult↗

PubMed1996

The participation of interleukin-6, a stress-inducible cytokine, in the pathogenesis of Alzheimer's disease.

A loss of synapses in the cortices of demented persons appears to be the primary correlate of Alzheimer's disease (AD). However, it is still unclear how synaptic pathology is connected to other pathological findings such as neurofibrillary and neuritic degeneration or inflammatory markers in AD. Interleukin-6 (IL-6) immunoreactivity has previously been detected in plaques in the brains of AD patients. In addition, elevated IL-6 concentrations have been measured biochemically in the brains of AD patients. Since transgenic mice bearing additional copies of the IL-6 gene under the control of a brain-specific promoter develop a marked cortical pathology including severe alterations of the dendritic arborization of cortical neurons, an IL-6 related inflammatory event could well be connected to the synaptic pathology in AD. In this study, we investigated whether IL-6 immunoreactivity in plaques could already be found prior to the onset of neuritic changes, or whether the presence of this cytokine is restricted to the later stages of plaque formation. While diffuse plaques represent an early stage of plaque formation, primitive and classic plaques (displaying neuritic pathology) are thought to reflect later stages of plaque pathology. Using a silver-staining method, we classified plaque stages in serial sections of paraffin-embedded cortices of clinically diagnosed and histopathologically confirmed AD patients and of control persons with no clinical history of dementia. Adjacent sections were stained with an antibody directed against IL-6. IL-6 was detectable in a significant proportion of plaques, but only in the brains of demented patients. In the AD cases, IL-6 was found in diffuse plaques in a significantly higher ratio as would have been expected from a random distribution of IL-6 among all plaque types. This observation suggests that IL-6 expression may precede neuritic changes and that in AD an immunological mechanism may be involved both in the transformation from diffuse to primitive plaques and in the development of dementia. The reasons for the increased expression of IL-6 in the brains of AD patients are still unknown. Basal IL-6 levels were found to be slightly elevated along normal aging. Based on several studies indicating that IL-6 expression is inducible also by psychological stress, one could speculate whether long-lasting stressful experiences may contribute to the pathological process underlying Alzheimer's disease.

Aged↗

PubMed1996

Stereotactic management of lesions of the pineal region.

OBJECTIVE: The relevance of the computed tomography-guided stereotactic approach for the management of lesions of the pineal region is analyzed. METHODS: In a retrospective analysis conducted between 1985 and 1993, the risk profile, the diagnostic accuracy, and the therapeutic relevance of the stereotactic approach in 106 patients was studied. Survival analysis was used to assess the reliability of the stereotactically obtained diagnosis in terms of follow-up observation. RESULTS: A histological diagnosis was obtained in 103 of the 106 patients. In three patients, a conclusive diagnosis could not be established because of intraoperative complications. One lesion was misdiagnosed as a pineocytoma instead of a pineoblastoma. Two of the 106 patients died; 9 patients experienced perioperative morbidity. In 38 patients, the stereotactic approach was also useful for therapy. Cyst aspiration and/or internal drainage was performed in 18 patients with symptomatic cystic lesions, and radiosurgical treatment with use of interstitial 125iodine was performed in 16 patients with low-grade tumors and in 4 patients with solitary metastases. In 12 patients, the obtained tissue diagnosis was the basis for deferring additional therapy. In 43 patients with germ-cell tumors, pineoblastomas, or malignant gliomas, a stereotactic biopsy was the starting point for additional radiotherapy/chemotherapy. Open tumor resection played a minor role (five patients). CONCLUSION: The stereotactic approach to the pineal region is a relatively safe procedure in experienced hands. The diagnosis obtained by computed tomography-guided stereotactic biopsy is a valid basis for treatment decisions. Long-term follow-up observation of the benign lesions is necessary for a definite confirmation of diagnostic accuracy.

Adolescent↗

PubMed1996

Differentiation of Purkinje cells in cerebellar slice cultures: an immunocytochemical and Golgi EM study.

In the rat central nervous system, the cerebellar cortex has a stereotypical cytoarchitecture and a characteristic connectivity pattern, both mainly formed post-natally. Organotypic cultures of immature cerebellar tissue were used to study the formation of the cerebellar lamination and the differentiation of Purkinje cells in the absence of their extracerebellar afferents. The lamination was retained in the majority of the cerebellar cultures and most Purkinje cells were aligned. Axonal profiles of Purkinje cells, immunolabelled for UCHT1 or anti-calbindin D-28 k, followed pathways similar to those in vivo cerebellum. The dendrites were orientated towards the superficial layer except of those neurons which were ectopically positioned. Unlike in vivo, the dendritic arborization of Golgi-impregnated/gold-toned or immunostained Purkinje cells was reduced and the dendritic spines were often elongated. Somatic spines, a morphological feature of immature Purkinje cells persisted even after 4 weeks in culture. We conclude that the Purkinje cells in organotypic cultures send their axon to the correct target region independent of their local position. In contrast, the dendritic orientation and differentiation is influenced by the cellular environment and by specific synaptic interaction.

Animals↗

PubMed1996

Deafness due to bilateral endolymphatic sac tumours in a case of von Hippel-Lindau syndrome.

A case of bilateral endolymphatic sac tumours is reported. In a patient with von Hippel-Lindau syndrome, tumour growth in the right cerebellopontine angle caused deafness. The tumour was removed and classified as a metastasis from a thyroid carcinoma. However, on thyroidectomy no primary neoplasm could be found. Eight years later a similar tumour was operated on in the left petrosal bone. Histological appearance, immunocytochemical findings, and the clinical context gave evidence that the tumours had to be reclassified as endolymphatic sac tumours--extremely rare entities. The report supports the hypothesis, suggested by the few earlier case reports, that endolymphatic sac tumours could be one of the inherent tumour manifestations in von Hippel-Lindau syndrome.

Carcinoma↗

PubMed1995

Phenytoin inhibits expression of microtubule-associated protein 2 and influences cell-viability and neurite growth of cultured cerebellar granule cells.

The objective of this study was to show whether an in vitro model for Phenytoin-related cytoskeletal impairment could be helpful to investigate cerebellar side effects of Phenytoin (DPH). DPH dose-and time-dependently resulted in decreasing numbers of vital cells. Cells formed only a rarefied intercellular neuritic network. This effect was already evident 24 h after plating. Western-blot analysis revealed that the expression of the dendritic marker microtubule-associated protein 2 (MAP2) was dramatically decreased in DPH-treated cultures.

Animals↗

PubMed1995

Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients.

Interleukin-6 (IL-6) immunoreactivity has previously been shown in plaques in Alzheimer's disease (AD) and elevated IL-6 concentrations have been measured biochemically in brains of AD patients. In this study, we investigated the appearance of IL-6 immunoreactivity in AD plaques according to the stage of plaque formation. Using the Bielschowsky silver-staining method, we were able to differentiate between four types of plaques described earlier: diffuse, primitive, classic and compact. While diffuse plaques represent the early stage of plaque formation, primitive and classic plaques are thought to represent later stages of plaque development. We investigated serial sections of paraffin-embedded cortices of ten clinically diagnosed and histopathologically confirmed AD patients and ten patients with no clinical history of dementia. We found plaques in the brains of both nondemented and demented persons using the silver staining method or immunohistochemistry with antibodies against the amyloid precursor protein. In the group of clinically nondemented persons, diffuse plaques were the predominant plaque type, whereas primitive plaques formed the larger portion of lesions in the group of AD brains. IL-6 could not be detected in plaques of patients without dementia. Many IL-6-positive plaques were found in six of the AD brains and to a smaller extent in the other four AD cases. In the six cases with a large number of IL-6-positive plaques, IL-6 was found in a significantly higher ratio of diffuse plaques than expected from a random distribution of IL-6 in all plaque types.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Ascending central nervous spreading of a spinal astrocytoma.

A 43-year-old man died from the complications of astrocytoma metastasis. He first noticed symptoms of a lumbar disc prolapse in 1979. In 1987 a pilocytic astrocytoma (grade I) of the spinal cauda was removed. In 1989 a tumor recidivation at the same site was partially removed. Histology showed a grade II astrocytoma. Two months later the patient developed symptoms of increased intracerebral pressure. CSF cytology showed polymorphic giant tumor cells with hyperchromatic nuclei and a glioblastoma of the cerebral ventricles was diagnosed. The patient died from cardiovascular complications. The post-mortem investigation revealed an astrocytoma of the conus medullaris with an anaplastic ventral area (grade IV). This area was inaccessible to the biopsy. It is believed that tumor metastases from anaplastic parts spread along the spinal cord and brainstem and finally invaded the brain and cerebral ventricles.

Adult↗

PubMed1995

Localization and characterization of cytochrome P450 in the brain. In vivo and in vitro investigations on phenytoin- and phenobarbital-inducible isoforms.

The antiepileptic drug phenytoin is known to be substrate as well as inducer of cytochrome P450 (P450) in the mammalian liver. We were able to show the expression of P450 species immunorelated to the main phenytoin-induced hepatic isoforms in mice (CYP2C29) and rats (CYP2B1,2) also in the central and peripheral nervous system and primary cultures of cell types from the brain. The 2B1,2 related protein showed only a weak constitutive expression in vivo and in vitro analyzed by immunocytochemistry, in situ hybridization, Northern blot and RT/polymerase chain reaction (PCR). Contrary, the CYP2C29 related form is inducible by phenytoin at about 1.5-fold starting from an already higher constitutive level. This protein is characterized by a remarkable tendency to dissociate from the endomembranes during tissue homogenization. The supernatant of microsomal pellet is able to metabolize phenytoin in a reconstitutive system.

Animals↗

PubMed1995

Studies for estimating the biologic behavior and prognosis of paragangliomas in the head and neck.

Despite a large number of histopathologic and immunohistochemical studies, the biologic behavior and prognosis of paragangliomas (glomus tumors) of the head and neck still remain uncertain. In the present study 36 specimens from 32 patients who underwent surgery for a paraganglioma were examined. The examinations included routine histology, quantitative DNA analysis based on image cytometry, immunohistochemical detection of the proliferating cell nuclear antigen (PCNA) along with visualization of nucleolar organizer regions (AgNOR). According to LeCompte, the paragangliomas were histologically divided into three subcategories: 16 patients had a paragangliomatous tumor. 14 patients had an adenomatous tumor, and 6 patients had an angiomatous tumor. Quantitative DNA analysis revealed three categories of tumors with characteristical DNA pattern; DNA type I tumors were pure diploid, DNA type II tumors had stemlines at 2c and 4c and were therefore recognized as diploid-tetraploid. Aneuploid cells were not apparent in these two groups. DNA type III tumors had stemline ploidies exceeding 2c and 4c. Aneuploid cells were present in all of these tumors. The biologic behavior of these lesions therefore must be recognized as suspicious. DNA type III tumors and adenomatous tumors showed the highest values for the PCNA scores, indicating a higher proliferation rate and a more rapid growth pattern in these lesions. Twenty patients could be followed over a period of up to 110 months. Five of these patients developed a recurrent tumor. All of them had DNA type III tumors. The DNA indices showed significantly higher values in the recurrent tumor group. The 2c deviation index (DI) and the entropy value had the highest prognostic significance. No correlation to clinical follow-up was found for the AgNOR score. Based on these results, prognostic indices for paragangliomas were developed: patients with a tumor having a 2c DI exceeding 2.0, entropy value of more than 4.0. 5c exceeding rate more than 8.0, and a PCNA score more than 20.0% can be recognized as being at high-risk for developing recurrent disease.

Journal Article↗

PubMed1995

Interstitial radiosurgery of low-grade gliomas.

The treatment of patients with low-grade gliomas remains a subject of controversy, especially with respect to new treatment modalities such as interstitial radiosurgery (brachytherapy), radiosurgery, and stereotactic radiotherapy. In a retrospective analysis conducted between 1979 and 1991, the authors studied the results of interstitial radiosurgery in 455 patients with low-grade gliomas (World Health Organization (WHO) Grade I+WHO Grade II) with regard to survival time, quality of life, the risk of malignant transformation, and the risk profile of the treatment concept. Interstitial radiosurgery with iodine-125 was performed using permanent (1979-1985) or temporary implants (after 1985) with low-dose rates (< or = 10 cGy/hr) and a reference dose of 60 to 100 Gy calculated to the outer rim of the tumor. The 5- and 10-year survival rates in patients with pilocytic astrocytomas (97 patients) were 84.9% and 83%, and in patients with WHO Grade II astrocytomas (250 patients) 61% and 51%, respectively. Five-year survival rates for patients with oligoastrocytomas (60 patients), oligodendrogliomas (27 patients), and gemistocytic astrocytomas (21 patients) were 49%, 50%, and 32%, respectively. In the group with WHO Grade II gliomas, young age and a good performance status were associated with a better prognosis. Unfavorable factors were midline shift, enhancement on computerized tomography (CT) scan, and tumor recurrence after previous radiotherapy or surgery. Tumor location had no influence on the prognosis (247 patients in this series had deep-seated tumors). Malignant transformation was the major cause of death. Important risk factors for malignancy were the patient's age, tumor enhancement in CT scan, and tumor recurrence after previous surgery or radiotherapy. Perioperative mortality was 0.9% and perioperative morbidity was 1.7%. Radiogenic complications were observed in 2.7% of all patients, most often in larger tumors and after using permanent implants. The authors conclude that interstitial radiosurgery represents a specific treatment modality for selected patients with unifocal circumscribed low-grade gliomas with a diameter of less than 4 cm in any location. The efficacy of this treatment lies in the same range as the best results after surgery and radiotherapy.

Adolescent↗

PubMed1995

Exclusively intracranial cranial fasciitis in a child. Case report.

The authors present a case of an intracranial tumor in a 7-year-old girl leading to increasing hemiparesis. The lesion arose from the dura and consisted of fibroblasts in a myxoid matrix. The diagnosis of cranial fasciitis was made. The histological, immunohistological, and ultrastructural features of the tumor are described and the differential diagnosis is discussed.

Brain Diseases↗

PubMed1995

Intermittent ethanol exposure of adult rats: hippocampal cell loss after one month of treatment.

The effects of intermittent intraperitoneal ethanol exposure (3 g/kg body weight twice daily) on hippocampal cells of adult rats were examined after a 1-month exposure period. Continuous oral exposure to ethanol in the drinking water (20%) over the same time period was used for comparison. Pyramidal cells from the CA3 region and granule cells from the dentate gyrus were also qualitatively assessed using electron microscopy. One month of intermittent, peaking, exposure induced a significant loss of CA2-CA3 pyramidal cells and an increase in the number of lipofuscin granules in the remaining cells. A significant reduction in thickness of the dentate gyrus granule cell layer was also seen in the same animals. No significant reduction in pyramidal cell number or granule cell layer thickness was seen in continuously orally exposed animals in spite of a higher total ethanol intake. These studies thus demonstrate the harmful effect of intermittent high ethanol peaks and repeated withdrawal phases on hippocampal cells of the mammalian brain and emphasize the importance of considering the differential effects of different ethanol exposure patterns when assessing ethanol-induced cellular damage.

Administration, Oral↗

PubMed1994

Cytochrome P450 in rat astrocytes in vivo and in vitro: intracellular localization and induction by phenytoin.

Cytochrome P450IIB1,2 (nomenclature according to Nelson et al., DNA Cell Biol 12:1-51, 1993 and Volk et al., Neuroscience 42:215-235, 1991) immunoreactivity (P450-IR) is associated with astrocytes both in vivo and in vitro. Although they are unevenly distributed throughout the brain with a preference for phylogenetically elder parts, no significant differences between astrocytes prepared from different brain regions were observed in astrocyte cultures. The percentage of strongly immunoreactive astrocytes decreased from 40% after 7 days in culture to 15% after 21 days. Essentially all astrocytes have a low but significant P450-IR within this interval. Preembedding immunoelectron microscopy revealed peroxidase reaction products on the endoplasmic reticulum and on the outer membranes of mitochondrial and nuclear envelopes. Phenytoin (1 microM) added to the medium for 7 days significantly (1.22-fold) increased the amount of total P450 in astrocyte homogenates as measured by spectrophotometry. Considerably more immunoreactive cells (1.5-fold) were found in treated cultures than in controls.

Animals↗