Biomedical subjects

P Wesseling

Publications and source records attributed to P Wesseling.

At least 55 records · Page 3Linked to original sources

PubMed1999

Agrin is a major heparan sulfate proteoglycan accumulating in Alzheimer's disease brain.

Heparan sulfate proteoglycans (HSPGs) have been suggested to play an important role in the formation and persistence of senile plaques and neurofibrillary tangles in dementia of the Alzheimer's type (DAT). We performed a comparative immunohistochemical analysis of the expression of the HSPGs agrin, perlecan, glypican-1, and syndecans 1-3 in the lesions of DAT brain neocortex and hippocampus. Using a panel of specific antibodies directed against the protein backbone of the various HSPG species and against the glycosaminoglycan (GAG) side-chains, we demonstrated the following. The basement membrane-associated HSPG, agrin, is widely expressed in senile plaques, neurofibrillary tangles and cerebral blood vessels, whereas the expression of the other basement membrane-associated HSPG, perlecan, is lacking in senile plaques and neurofibrillary tangles and is restricted to the cerebral vasculature. Glypican and three different syndecans, all cell membrane-associated HSPG species, are also expressed in senile plaques and neurofibrillary tangles, albeit at a lower frequency than agrin. Heparan sulfate GAG side chains are also associated with both senile plaques and neurofibrillary tangles. Our results suggest that glycosaminoglycan side chains of the HSPGs agrin, syndecan, and glypican, but not perlecan, may play an important role in the formation of both senile plaques and neurofibrillary tangles. In addition, we speculate that agrin, because it contains nine protease-inhibiting domains, may protect the protein aggregates in senile plaques and neurofibrillary tangles against extracellular proteolytic degradation, leading to the persistence of these deposits.

Aged↗

PubMed1999

A new technique for the assessment of the draining area of a cerebral vein.

BACKGROUND: At present, it is not exactly clear which vein is allocated for drainage of blood to a particular area of the human brain. Knowledge of these draining areas is very important for the understanding of occlusive venous diseases. A method was developed that offers the possibility to investigate the draining area of a cerebral vein, with the help of an animal model. METHODS: Brains of sacrificed rabbits are removed and are anterogradely perfused with a coloring matter. Then a vein chosen at random is occluded and anterograde perfusion is restarted using another coloring substance. The working hypothesis is that the part of the brain that is solely dependent for its drainage of blood upon the occluded vein (the draining area of the vein) will show a deficit in staining after the second perfusion. RESULTS Using the abovementioned technique, no filling defect was seen if a vein was occluded near its entrance into the sinus (N = 8) or at a single point over the cortex (N = 7). If a longer trajectory (10-14 mm.) was obstructed, a clear staining defect was seen in 13 out of 16 hemispheres; the three remaining cases seemed to be technical failures. CONCLUSION: A new method is described to investigate the draining area of a cerebral vein. Although the validity of the method is proven in an animal model, it seems a good technique for investigation of human brains postmortem. Application of this technique will contribute to the understanding of the pathophysiology of venous diseases and also elucidate the role of the venous anastomotic pathways.

Animals↗

PubMed1999

Suramin treatment of human glioma xenografts; effects on tumor vasculature and oxygenation status.

In this study the effect of suramin on tumor growth, vascularity and oxygenation of a human glioma xenografted in the nude mouse was examined. Vascular parameters and oxygenation status of the xenografts were determined immunohistochemically in frozen sections of the tumors, using the hypoxia marker pimonidazole-hydrochloride to detect hypoxic areas. Tumor vessels in these sections were stained by an endothelial cell marker and perfusion of vessels was visualized by administration of the perfusion marker Hoechst 333342 before harvesting the tumors. The vascular parameters were quantified with an image analysis system. The results show that tumor growth was reduced considerably after suramin treatment. This growth suppression was accompanied by marked changes in vascular architecture. Although the total vascular area and perfused fraction of tumor vessels remained unchanged after suramin treatment, vascular density increased, indicating that more but smaller vessel structures had developed during therapy. These vessel structures were also more homogeneously spread over the tumor area. Control tumors showed extensive areas of hypoxia while in treated tumors hypoxic areas had mostly disappeared. This effect was probably due to the higher density of homogeneously distributed perfused vessel structures in the treated tumors, contributing to an increased oxygenation of the tumor. These observations suggest that suramin therapy can result in marked changes not only in tumor vascularity but also in tumor oxygenation status which may have important consequences for sensitivity of these tumors to other therapies such as radiation treatment.

Animals↗

PubMed1999

Spinal xanthomatosis: a variant of cerebrotendinous xanthomatosis.

We describe seven Dutch patients from six families with a slowly progressive, mainly spinal cord syndrome that remained for many years the sole expression of cerebrotendinous xanthomatosis (CTX). MRI demonstrated white matter abnormalities in the lateral and dorsal columns of the spinal cord. Post-mortem examination of one of the patients showed extensive myelin loss in these columns. An array of genotypes was found in these patients. We conclude that 'spinal xanthomatosis' is a clinical and radiological separate entity of CTX that should be included in the differential diagnosis of 'chronic myelopathy'.

Adult↗

PubMed1999

Identification of subgroups of high-grade oligodendroglial tumors by comparative genomic hybridization.

In contrast to astrocytic tumors, approximately two thirds of anaplastic oligodendrogliomas are reported to be chemosensitive. Relatively little is known about the genetic aberrations in oligodendroglial tumors (OTs). In order to elucidate oligodendroglial oncogenesis and to find specific genetic aberrations that may have prognostic and therapeutic implications, we performed comparative genomic hybridization (CGH) to detect chromosomal copy number changes in 17 low-grade OTs (LG-OTs) and 12 high-grade OTs (HG-OTs) lacking a prominent astrocytic component. Loss of chromosome 1p (79%) and 19q (76%) were most frequently detected by CGH, all LG-OTs and 50% of the HG-OTs contained -1p (including 1p36-32), -19q (including 19q13.3), or both, and the rest of the HG-OTs showed +7, -10, or both. Since losses of 1p36-32 and 19q13.3 were mutually exclusive with +7 or -10, the HG-OTs could be divided in -1p/-19q and +7/-10 tumors. While the -1p/-19q tumors can be considered as pure anaplastic oligodendrogliomas, the +7/-10 tumors may rather be glioblastomas with prominent oligodendroglial differentiation. We conclude that CGH is a powerful tool to assist in the identification of 2 major subgroups of HG-OTs with prognostic and possibly therapeutic relevance.

Chromosome Aberrations↗

PubMed1999

Meningioma of the pituitary stalk without dural attachment: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Tumors in the suprasellar region such as adenomas of the pituitary gland, craniopharyngiomas, nonneoplastic cystic lesions (especially Rathke's cleft cysts), and meningiomas are frequently encountered in neurosurgical practice. Meningiomas originate from the arachnoid layer connected to the dura of the anterior or posterior clinoidal process, or the tuberculum, dorsum, or diaphragma sellae. Tumors originating from the pituitary stalk are rare. Such lesions may include germinomas, astrocytomas, histiocytosis X, hamartomas, and sarcoidosis. We report a patient with a suprasellar meningioma originating from the pituitary stalk with no connection to the adjacent dura. CLINICAL PRESENTATION: A 50-year-old man was assessed for impotence and loss of libido. Physical examination revealed no abnormalities. Endocrinological investigations disclosed nearly complete hypopituitarism, and magnetic resonance imaging revealed a suprasellar homogeneously enhancing tumor. INTERVENTION: Complete surgical resection was performed in an endoscope-assisted right-sided supraorbital craniotomy. The tumor originated from the pituitary stalk with no connection to the surrounding dura. The histopathological diagnosis was meningioma. CONCLUSION: Although meningiomas frequently occur in the suprasellar region, this patient with a suprasellar meningioma is unique because the tumor originated from the pituitary stalk with no connection to the surrounding dura. The absence of dural attachment has been described in 43 extracerebral meningiomas, but a suprasellar location has been reported only once previously. Recognition of this phenomenon is important, because meningiomas require a different therapeutic strategy than most other tumors of the pituitary stalk.

Craniotomy↗

PubMed1999

Transalar sphenoidal encephalocele and respiratory distress in a neonate: a case report.

We present a full-term newborn infant who suffered from immediate postpartum severe respiratory distress. The infant had an inspiratory stridor as a result of a swelling of the soft palate, extending from the roof of the nasopharynx. Transoral endotracheal intubation resulted in normal saturation levels. Histologic examination after an open biopsy showed mature neuroglial tissue. Radiology demonstrated the presence of a right parapharyngeal process obstructing the nasopharynx and oropharynx and extending to the right middle and posterior fossa, via the foramen ovale. After transoral debulking, the infant was extubated successfully. After an uneventful period of 5 months, the patient was readmitted at our hospital for treatment of meningitis. Subsequently, the inspiratory stridor recurred, and staged surgery was performed. First, a transcranial approach was used to remove a large intradural part of the process and close the defect at Meckel's cave. Two weeks later the retro- and parapharyngeal part of the process were removed transorally. Given the site of the defect of the skull base and the intradural location of the process, the diagnosis is a transalar sphenoidal encephalocele. This is a rare type of basal encephalocele, and has never been reported in an infant nor known to present with respiratory distress. The pathogenesis, clinical presentation, pathology, and therapeutic implications of basal encephaloceles are discussed.

Encephalocele↗

PubMed1999

A new X linked neurodegenerative syndrome with mental retardation, blindness, convulsions, spasticity, mild hypomyelination, and early death maps to the pericentromeric region.

We report on a family with an X linked neurodegenerative disorder consisting of mental retardation, blindness, convulsions, spasticity, and early death. Neuropathological examination showed mild hypomyelination. By linkage analysis, the underlying genetic defect could be assigned to the pericentromeric region of the X chromosome with a maximum lod score of 3.30 at theta=0.0 for the DXS1204 locus with DXS337 and PGK1P1 as flanking markers.

Blindness↗

PubMed1998

Infantile motor neuron disease with autonomic dysfunction and bunina bodies.

A 2-month-old girl developed motor neuron disease (MND) with autonomic disturbances and died at the age of 5 months. Neuropathological examination revealed Bunina bodies (BBs) in the lower motor neurons of the lumbar spinal cord. The significance of the presence of BBs and the classification of the MND in this child are discussed.

Autonomic Nervous System Diseases↗

PubMed1998

Quantitative analysis of microvascular changes in diffuse astrocytic neoplasms with increasing grade of malignancy.

Because glioblastoma multiforme (GBM) frequently shows striking, glomeruloid microvascular proliferation (MVP), this tumor has become a strong candidate for anti-angiogenic therapy. However, the efficacy of anti-angiogenic treatment may rather be determined by the extent of classic angiogenesis with the formation of delicate microvascular sprouts. Therefore, this study differentially quantifies the microvascular changes in supratentorial diffuse astrocytic neoplasms by computerized image analysis of histological sections in which the microvessels were highlighted by a combined anti-collagen IV/MIB-1 staining. Four microvascular parameters (number, area, perimeter, diameter), the cellularity of the glial tissue, and the MIB-1 labeling index were assessed in biopsies of astrocytoma (A, n = 13), anaplastic astrocytoma (AA, n = 14), and GBM (n = 20), and in normal cerebral cortex (n = 7) and white matter (n = 7). In As and AAs, the microvascular parameters were not significantly different from each other, and the microvascular changes were generally limited compared with WM and CX. In contrast, in GBMs the microvascular parameters were highly variable, and their overall mean value was significantly increased compared with As and AAs (ranging from 1.3x for vessel diameter to 3.3x for vessel area). Our study indicates that not only glomeruloid MVP, but also classic angiogenesis, occurs mainly and only locally in GBMs. Thus, this study provides evidence that As and AAs are not good candidates for anti-angiogenic therapy. The efficacy of such therapy for GBMs awaits further evaluation.

Antigens, Nuclear↗

PubMed1998

Ileus in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes.

PATIENT: A 39-year-old woman with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) who developed paralytic ileus and died of irreversible shock. METHODS: Abdominal X-ray, autopsy using light microscopy, electron microscopy and mitochondrial DNA analysis. RESULTS: Paralytic ileus was diagnosed. Several hours after admission the patient died from irreversible shock. At autopsy, ultrastructural examination of the small intestine revealed abnormal accumulation of mitochondria in smooth muscle cells. DNA analysis of the intestinal tissue showed a tRNALeu(UUR) A-->G transition at nucleotide position 3243 of the mitochondrial DNA. The amount of mutated mitochondrial DNA was markedly higher in the lamina muscularis than in the mucosa: 30% vs; 8%. CONCLUSIONS: Paralytic ileus may be due to mutated mitochondrial DNA which ultimately leads to smooth muscle dysfunction in the small intestine. Recognizing mitochondrial DNA abnormalities as a new etiopathogenetic factor of paralytic ileus may become more important in clinical medicine in the near future.

Adult↗

PubMed1998

A uniform histological cluster scheme for ICD-O-coded primary central nervous system tumors.

Comparability of population-based measures of risk and prognosis for primary central nervous system (CNS) tumors, which exhibit marked histological diversity, may be hampered by differences in detection and case ascertainment and by the lack of unequivocal and uniform histological criteria for pathological diagnoses. Furthermore, many cancer registries do not include benign tumors as defined by the International Classification of Diseases for Oncology (ICD-O), such as meningiomas, schwannomas and pituitary adenomas. We propose both a detailed and a rough uniform histological cluster scheme for data coded according to the first or second edition of the ICD-O, published in 1976 and 1990, respectively. Primary CNS tumors, typed and graded according to (modified) classification systems of Bailey and Cushing, Kernohan, Ringertz, the WHO and Daumas-Duport, are clustered as clinically relevant entities on the basis of the second edition of the WHO classification system, published in 1993. The proposed scheme identifies some of the (potential) pitfalls in the descriptive epidemiology of CNS tumors and may facilitate temporal and geographical comparability of population-based data.

Central Nervous System Neoplasms↗

PubMed1997

The Aircardi-Goutières syndrome: variable clinical expression in two siblings.

We report 2 siblings with the Aicardi-Goutières syndrome (encephalopathy, basal ganglia calcifications, and persistent cerebrospinal fluid pleiocytosis). The eldest sibling is severely retarded; his younger brother has only mild, slowly progressive neurological deficits. To our knowledge, such a striking difference in clinical expression has not been reported previously.

Basal Ganglia Diseases↗

PubMed1997

Angiogenesis in brain tumors; pathobiological and clinical aspects.

Angiogenesis is the outgrowth of new blood vessels from the preexistent vasculature. In 1971, Folkman hypothesized that solid tumors are dependent on angiogenesis for sustained growth and that anti-angiogenic treatment is a potential antineoplastic therapy. Because glioblastoma multiforma (GBM) frequently shows florid microvascular proliferation (MVP), this tumor has been considered since then as a suitable candidate for such treatment that attempts to eradicate or control a neoplasm by interfering with its blood supply. Indeed, in animal models the growth of glioma xenografts can be inhibited by targeting the angiogenic process. However, unlike many glioma xenografts, human infiltrating gliomas such as GBMs have a diffuse infiltrative growth pattern, and preexistent vessels may suffice to provide many tumor cells with much of their blood supply, particularly in the critical peripheral infiltrative margins. Thus, while attractive in concept, anti-angiogenic therapy of GBM must address the anatomic vascular realities of this neoplasm. Even if anti-angiogenic therapy ultimately has a role in infiltrative neoplasms, there are a host of other intracranial neoplasms whose discrete architecture might make them attractive candidates for anti-angiogenic therapy. This review summarizes the angiogenic process in GBM and suggests other types of tumors for which the efficacy of anti-angiogenic therapy might be studied.

Brain Neoplasms↗

PubMed1997

Vascular density in melanoma xenografts correlates with vascular permeability factor expression but not with metastatic potential.

We studied the relation between tumour vascular density and tumour growth rate, metastatic incidence and vascular permeability factor (VPF) mRNA levels in a human xenograft model described previously. Vascular density was determined by automated image analysis. Xenografts derived from cell lines BLM and MV3 showed the highest mean vascular density (MVD), the highest in vivo growth rate, high VPF mRNA levels and rapid development of lung metastases. Xenografts of cell lines M14, Mel57 and MV1 showed a significantly lower degree of vascularization, lower in vivo growth rates and lower levels of VPF mRNA, but formed lung metastases with a similar incidence as those of BLM and MV3. Xenografts from cell line 1F6 did not form lung metastases, whereas tumours derived from a spontaneous mutant of 1F6, designated 1F6m, gave rise to lung metastases to the same extent as Mel57, M14 and MV1 tumours. MVD values in 1F6 and 1F6m xenografts, VPF mRNA levels and in vivo growth rates of 1F6 and 1 F6m xenografts, however, were similar. In conclusion, in the melanoma xenograft model vascular density is correlated with in vivo growth rate and with in vitro VPF mRNA levels, but not with the ability to metastasize.

Animals↗

PubMed1997

Severe keratitis due to Nocardia farcinica.

Keratitis due to Nocardia farcinica occurred in a 49-year-old female after inappropriate cleaning of her semipermeable rigid contact lenses with basin-stored water during a holiday in France. N. farcinica was differentiated from Nocardia asteroides by its growth at 45 degrees C, acid production from rhamnose, its opacification of Middlebrook 7H10 agar, and its marked degree of resistance to all cephalosporins, aminoglycosides, tetracyclins, macrolides, and trimethoprim-sulfamethoxazole. To the best of our knowledge, this is the first reported case of human N. farcinica keratitis, confirming that this microorganism can be responsible for serious human disease.

Contact Lenses↗

PubMed1996

Aminopeptidase a is a constituent of activated pericytes in angiogenesis.

Monoclonal antibody (MAb) RC38 recognizes a human renal antigen of 160 kD recently identified as human aminopeptidase A (APA; EC 3.4.11.7). This ectoenzyme is able to hydrolyse selectively N-terminal glutamyl and aspartyl residues from oligopeptides. By enzyme histochemistry, APA activity has also been localized in the microvessels of all organs in animals and man. The purpose of this study was to investigate the distribution of human APA as recognized by MAb RC38 in the microvasculature of normal human tissues and pathological conditions associated with neovascularization. Unexpectedly, in normal tissues vascular staining with MAb RC38 was generally weak and often absent, while in tumours, granulation tissue, and chronic synovitis, marked microvascular staining was demonstrated. By immuno-electron microscopy, the antigen was found on the cell membrane of activated pericytes and their processes in the tumour vasculature. RC38 expression could not be detected on cultured human endothelial cells or pericytes. These observations suggest that pericyte expression of a subtype of APA (as recognized by MAb RC38) is markedly enhanced in the vasculature of tumours and wound healing tissue as compared with normal resting tissues. This provides further evidence of the altered state of pericytes in these conditions. Pericyte APA may be involved in the metabolism of biologically active oligopeptides during neovascularization, supporting a regulatory role of pericytes in this process. In addition, MAb RC38 may be useful as a marker of pericyte activation in tissue sections.

Aminopeptidases↗

PubMed1996

Differential expression of intercellular adhesion molecule-1 (ICAM-1) in the A beta-containing lesions in brains of patients with dementia of the Alzheimer type.

Inflammatory processes have been implicated in the formation of senile plaques in the cerebral cortex of patients with dementia of the Alzheimer type (DAT), since several inflammation-induced proteins are present within these plaques. The relation between inflammatory components and other amyloid beta protein (A beta)-containing lesions of the DAT brain [cerebrovascular amyloidosis (CA) and cerebellar senile plaques] is unclear. We studied the distribution of the inflammation-inducible protein intercellular adhesion molecule-1 (ICAM-1) in CA and in senile plaques of the cerebellum, using an immunohistochemical approach. We observed striking differences in ICAM-1 reactivity between the different types of A beta-containing lesions. ICAM-1 was only expressed in classic senile plaques in the granular and Purkinje cell layer of the cerebellum, and not in diffuse senile plaques of the molecular layer. Also, ICAM-1 was not associated with CA; only when the vascular amyloid extended into the neuropil (dyshoric angiopathy) was perivascular ICAM-1 reactivity observed. This is in contrast to the putative primary involvement of inflammation in the formation of cerebrocortical classic and diffuse senile plaques. Our findings indicate that ICAM-1 expression, which may be an indicator of an inflammatory reaction, is induced in the neuropil depending on the specific site of A beta production.

Aged↗