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Biomedical subjects

P Wesseling

Publications and source records attributed to P Wesseling.

70 records · Page 4Linked to original sources
PubMed1996

Choroid plexus carcinoma: a report of two cases and review of the literature.

Choroid plexus carcinoma is a rare intracranial neoplasm, affecting mainly very young children. The most common site of origin is within one of the lateral ventricles. The diagnosis of choroid plexus carcinoma is based on histological examination. Frequently subarachnoid seeding occurs and investigation at diagnosis should include examination of the cerebrospinal fluid and magnetic resonance imaging of the spinal cord. Extraneural metastases are rare. Prognosis for long-term survival ameliorates. Total surgical resection of the tumor should be attempted. Both radiotherapy and chemotherapy are used as adjuvant therapies for primary tumors. No clear difference in effectiveness of these therapies could be found. However craniospinal irradiation seems to be more effective when leptomeningeal seeding is present.

Biomarkers, Tumor↗
PubMed1996

Mitochondrial cytopathy presenting as hereditary sensory neuropathy with progressive external ophthalmoplegia, ataxia and fatal myoclonic epileptic status.

We present six adult patients from three separate families, with a remarkably uniform heredo-ataxic syndrome, developing in three stages and ending in early death. The initial stage is determined by severe sensory neuropathy. The second stage is characterized further by progressive external ophthalmoplegia (PEO), probably caused by ocular myopathy, and progressive ataxia. During a short last stage there is epilepsia, and particularly myoclonic status epilepticus, of which four patients died unexpectedly. Sural nerve biopsies showed severe loss of myelinated fibres in a rather early stage of disease. Skeletal muscle biopsies (and a specimen of ocular muscle) revealed ragged-red fibres. Autopsy examination in two patients revealed multisystemic involvement of the nervous system, with, in particular, degeneration of spinal dorsal columns and spinocerebellar tracts. Pedigree data were compatible with an autosomal recessive disorder. Additional findings, particularly elevation of CSF lactate, suggested mitochondrial cytopathy as an essential feature of the multisystem degeneration in these patients.

Adolescent↗
PubMed1995

A lysosomal marker for activated microglial cells involved in Alzheimer classic senile plaques.

One of the major histopathological lesions in brains of patients with dementia of the Alzheimer type (DAT) is the senile plaque. Although previous studies have shown that senile plaques are often accompanied by microglial cells, the role of these cells in DAT pathology is still unclear. In an immunohistochemical and immunoelectron microscopical analysis of DAT and control brain tissues we addressed this issue using two monoclonal antibodies (mAbs KP1 and 25F9) directed against lysosomal antigens in monocytes and macrophages. Whereas KP1 stained lysosomes in both resting and activated microglial cells, 25F9-staining was predominantly found in lysosomes of activated microglial cells in classic senile plaques. The number and size of 25F9-positive lysosomes in activated microglial cells was increased compared to 25F9-staining in unaffected areas in DAT and control sections. We conclude that mAb 25F9 is a unique and useful lysosomal marker, with a higher specificity than other known markers, for activated microglial cells associated with classic, but not with diffuse, senile plaques.

Aged↗
PubMed1995

Conventional radiotherapy combined with carbogen breathing and nicotinamide for malignant gliomas.

High grade malignant gliomas are among the most radioresistant human tumors and total doses up to 80 Gy are inadequate to achieve long-term local control in most of the patients. Hypoxia has been demonstrated in primary brain tumors and may be one of the reasons for their radioresistance. In experimental models carbogen breathing and nicotinamide have been shown to act against hypoxia by different mechanisms and both modalities were tested in 16 patients with supratentorial malignant gliomas in combination with a conventional radiotherapy scheme (50 Gy in 25 daily fractions). The present study was performed to determine the feasibility and toxicity of conventional radiotherapy combined with carbogen breathing and nicotinamide. The unexpectedly high incidence of acute liver toxicity, the possible increase of subacute and late CNS toxicity, and the absence of a higher effectivity led us to reconsider this new treatment modality for patients with malignant gliomas.

Administration, Inhalation↗
PubMed1995

Hypokinesia and presenile dementia in a Dutch family with a novel insertion in the prion protein gene.

The clinical features and disease course of six patients from a family with autosomal dominant inheritance of presenile dementia and a hypokinetic syndrome are described. In the past, these patients have carried diagnoses of Pick's disease, Huntington's disease, Parkinson-dementia, and one patient was described as suffering from a 'peculiar type of presenile dementia' in a case report. In the two cases examined, the most distinctive neuropathological features were extensive globular deposits of periodic acid-Schiff plus diastase (PAS)-positive material, having tinctural properties of amyloid only to a limited degree, in the cerebellum and cerebral cortex. These globules stained positively with antibodies against prion protein. Southern blot of MspI-digested genomic DNA showed an abnormal band of approximately 950 bp in all three patients from which material was available. Direct sequencing of the abnormal allele revealed an insert consisting of eight extra 24-nucleotide repeats in the patients, which was absent in a healthy first degree relative who was considered well beyond the age of onset of symptoms in this family. The nucleotide sequence of the abnormal insert of 192 bp was different from that of a previously described insert of equal length. Adding to previous descriptions of mutations in the prion protein gene, this report emphasizes the clinical, neuropathological and genetic heterogeneity of inherited prion disease.

Adult↗
PubMed1995

Early and extensive contribution of pericytes/vascular smooth muscle cells to microvascular proliferation in glioblastoma multiforme: an immuno-light and immuno-electron microscopic study.

Although florid microvascular proliferation (MVP) in glioblastoma multiforme (GBM) has long been considered as proliferation of endothelial cells (EC), recent immuno-light microscopic studies demonstrated many alpha-smooth muscle actin (alpha-sm actin)-positive cells in this MVP, suggesting a major contribution of pericytes and/or vascular smooth muscle cells (VSMC). Under certain culture conditions, however, alpha-sm actin expression has also been described in EC. In order to further investigate to what extent pericytes/VSMC participate in MVP in GBM, we performed an immunohistochemical study at both the light and electron microscopic levels with anti-alpha-sm actin, with an antibody against EC (EN-4) and with an antibody recently described to react with "activated" pericytes in conditions with neovascularization (anti-high molecular weight-melanoma associated antigen). In this detailed study of MVP in GBM, two distinct cell types could be recognized on the basis of a consistent ultrastructural localization and immunophenotype: EC and pericytes/VSMC; no transitional forms were found between these two cell types. The contribution of pericytes/VSMC to MVP in GBM was extensive and already present in many delicate tumor capillaries, suggesting not only an essential but also an early role of these cells in this type of tumor angiogenesis.

Antigens, Neoplasm↗
PubMed1994

Quantitative immunohistological analysis of the microvasculature in untreated human glioblastoma multiforme. Computer-assisted image analysis of whole-tumor sections.

Because histologically prominent microvascular proliferation is frequently present in glioblastoma multiforme, it has been hypothesized that this neoplasm is particularly dependent on neovascularization for its continued growth and that antiangiogenic therapy might be especially useful. To quantify the histological aspects of microvascular proliferation in glioma, a feasible and reproducible method was developed for computer-assisted image analysis of the visualized microvasculature in glial tissue. This method was used to compare several vascular parameters in histological whole-tumor sections of untreated human glioblastoma multiforme with those in histologically normal cerebral cortex and white matter. There was a significant increase in mean number, area, and perimeter of blood vessels per microscopic field in glioblastoma multiforme compared to normal cerebral white matter. In a substantial number of tumor fields, however, the vascular density was in the same range as that of normal cerebral white matter. The striking heterogeneity of the microvasculature within glioblastoma multiforme was illustrated by the significantly higher standard deviation for the vascular parameters in tumor tissue. The results of this study suggest that many regions of glioblastomas multiforme are not overtly angiogenesis dependent and may be difficult to treat by antiangiogenic therapy alone.

Adult↗
PubMed1994

Accumulation of intercellular adhesion molecule-1 in senile plaques in brain tissue of patients with Alzheimer's disease.

The still unsolved pathogenesis of Alzheimer's disease (AD) has been the subject of extensive speculation. Some years ago, a local acute phase reaction involving production of interleukin-1 (IL-1) and IL-6 was proposed as the triggering event in AD. Since it has been reported that these cytokines induce expression of intercellular adhesion molecule-1 (ICAM-1), we analyzed AD brain tissue cryosections for the presence of ICAM-1 by immunostaining and for ICAM-2 expression as a control. In senile plaques a marked diffuse or granular staining for the ICAM-1 domains 1, 4, and 5 was observed, whereas ICAM-2 expression was observed in microglial cells. Immunoprecipitation analysis demonstrated the presence of a 85 kd ICAM-1 molecule in AD frontal cortex. Our findings indicate that ICAM-1 accumulates in senile plaques as a complete 5-domain molecule at a relatively early stage of senile plaque formation. Our results are in support of a cytokine-mediated pathogenesis of senile plaque formation.

Adolescent↗
PubMed1994

Induction of alpha-smooth muscle actin expression in cultured human brain pericytes by transforming growth factor-beta 1.

Pericytes are cells localized at the abluminal side of the microvascular endothelium and completely enveloped by a basement membrane. Pericytes have close contact with endothelial cells and are probably involved in the regulation of endothelial cell functions. Previous studies suggested a role for pericytes in microvascular proliferation in tumors. To study this cell type, we isolated human brain pericytes from microvessel segments derived from autopsy brain tissue. These cells were characterized in vitro using a panel of monoclonal antibodies. Human brain pericytes were reactive with monoclonal antibodies directed against the high molecular weight-melanoma associated antigen and intercellular adhesion molecule-1, but only a minority of the cells expressed alpha-smooth muscle actin (alpha-SMA, 0 to 10%) or vascular cell adhesion molecule-1 (10 to 50%). In histologically normal human brain microvessels in situ, pericytes consistently lacked staining for these four markers. Tissue with microvascular proliferation, however, showed a marked pericyte staining for both alpha-SMA and high molecular weight-melanoma associated antigen. The expression of alpha-SMA in vitro could be slightly up-regulated by incubation with serum-containing medium. An increase in alpha-SMA expression up to 40% of the total cell population was seen when pericytes were treated with transforming growth factor-beta 1, whereas basic fibroblast growth factor slightly inhibited alpha-SMA expression. Incubation with other factors (platelet-derived growth factor-AA, heparin, interferon-gamma, tumor necrosis factor-alpha) had no effect on the alpha-SMA expression at all. Transforming growth factor-beta 1 thus induces smooth muscle-like differentiation in pericytes in vitro and might play a role in the activation of pericytes during angiogenesis in vivo.

Actins↗
PubMed1993

Cellular components of microvascular proliferation in human glial and metastatic brain neoplasms. A light microscopic and immunohistochemical study of formalin-fixed, routinely processed material.

Since the origin of cells contributing to microvascular proliferation (MVP) in glial neoplasms is unsettled, a light microscopic and immunohistochemical study for vascular smooth muscle cells and endothelial cells was performed in formalin-fixed, routinely processed brain tumor biopsy material. MVP in glial neoplasms was compared with that in intracerebral metastatic carcinomas and in intracranial granulation tissue. On the basis of the degree of hyperplasia of hypertrophic cells in the microvascular wall, MVP was subjectively divided into mild, moderate, and glomeruloid (marked) proliferation. The relative contribution of vascular smooth muscle cells and endothelial cells to different degrees of MVP was estimated immunohistochemically using antibodies against alpha-smooth muscle actin and von Willebrand factor, respectively. Glomeruloid MVP occurred in 50% of the malignant glial neoplasms. Moderate MVP was found in most malignant gliomas and in some pilocytic astrocytomas. Glomeruloid MVP was present in peritumoral glial tissue in 4 out of 15 intracerebral metastatic carcinomas, while only mild to moderate MVP was found within these tumors. In granulation tissue MVP was mild. In glomeruloid and moderate MVP vascular smooth muscle cells were more hypertrophic and more numerous than endothelial cells. The contribution of hypertrophic vascular smooth muscle cells to mild MVP was variable. MVP in glial neoplasms was generally not accompanied by a matrix of fibrous stroma but was directly embedded in glial tissue. The architecture of this MVP suggested "in situ" proliferation of microvascular cells without migration of these cells into the surrounding tissue.

Actins↗
PubMed1988

Double-blind comparison of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid suppositories in patients with idiopathic proctitis.

Suppositories containing 300 mg 5-aminosalicylic acid (1.96 mmol) or 425 mg acetyl-5-aminosalicylic acid (1.96 mmol) were used in 40 patients with idiopathic proctitis to determine the efficacy of acetyl-5-aminosalicylic acid in treating this bowel inflammation. Each patient was treated with 5-aminosalicylic acid or acetyl-5-aminosalicylic acid suppositories twice daily for 4 weeks in a double-blind trial. Four patients were included twice in the trial. The second time they were treated with the alternative regimen. Six patients in the acetyl-5-aminosalicylic acid group did not complete the trial, four of them because of diarrhoea. Complete clinical remission with normal rectal mucosa on sigmoidoscopy was achieved in 10 out of 18 patients on 5-aminosalicylic acid and in only two out of 15 in the acetyl-5-aminosalicylic acid group (P = 0.03). A favourable histological improvement was demonstrated with 5-aminosalicylic acid suppositories, but the difference with acetyl-5-aminosalicylic acid was not significant (P = 0.059). Three of the four patients who received both drugs recovered with 5-aminosalicylic acid; in none of them was acetyl-5-aminosalicylic acid effective. The results from this study and from previous investigations show that acetyl-5-aminosalicylic acid is not superior to placebo.

Adult↗
PubMedDate not supplied

Postmortem findings in the Nijmegen breakage syndrome.

Autopsy findings for two patients with the Nijmegen breakage syndrome (NBS) are presented. This syndrome has the same type of immunologic and cytogenetic abnormalities as ataxia telangiectasia (AT). In NBS, however, microcephaly is found and progressive cerebellar ataxia and oculocutaneous telangiectasia are lacking. We demonstrate a clear neuropathologic difference between these two syndromes, as the diffuse cortical cerebellar degeneration characteristic of AT was absent in NBS. In the thymus the histologic picture was suggestive of simple dysplasia. Lymphoid tissues were slightly atrophic but otherwise structurally normal. In one of the two presented cases an extranodal diffuse large cell malignant non-Hodgkin lymphoma of B cell immunoblastic type was found in Waldeyer's ring, in the small and large intestines, and in the brain, whose sequelae had caused death. Six of the 19 patients known with certainty to have this syndrome have developed lymphoid malignancy, which indicates that these patients are prone to develop malignancies.

Abnormalities, Multiple↗
PubMedDate not supplied

A case of Joubert's syndrome with extensive cerebral malformations.

Joubert's syndrome is a relatively rare, autosomal-recessive syndrome defined by vermis hypoplasia, hypotonia, developmental delay and at least one of two additional manifestations: abnormal breathing pattern or abnormal eye movements. Detailed descriptions of the neuropathological findings in this syndrome are scarce. We present a radiological and pathological correlation of a case of Joubert's syndrome in which, apart from the classic vermis aplasia and some malformations of the brain stem and the spinal cord, extensive malformations of the cerebrum were found. The dentate nuclei were broken into islands and showed a few heterotopias within the superior cerebellar pedunculi, the inferior olives were plump and dysplastic, and an almost complete absence of the pyramidal decussation was found. In the spinal cord, the dorsal columns were located in a dorsal position within the spinal grey matter. In the cerebrum, absence of the corpus callosum was found. Many nodular heterotopias of the cerebral cortex and of the basal ganglia, the amygdala and the diencephalon were observed. The present case is compared to previous pathological descriptions of the Joubert syndrome and to other syndromes with comparable malformations of the posterior fossa.

Abnormalities, Multiple↗
PubMedDate not supplied

Myelopathy due to spinal epidural abscess without cord compression: a diagnostic pitfall.

Spinal epidural abscess (SEA) is a neurological emergency that requires urgent diagnosis and treatment. We report 2 patients with SEA, in whom, on neuropathological examination, the neurological signs were found to be caused by spinal cord ischemia due to thrombosis of leptomeningeal vessels and compression of spinal arteries, respectively, while evidence of spinal cord compression was absent. Clinicians and neuropathologists should be aware of the variable mechanisms underlying the neurological involvement in SEA. Absence of spinal cord compression by the abscess may hamper early diagnosis and treatment.

Aged↗