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P Van der Valk

Publications and source records attributed to P Van der Valk.

18 recordsLinked to original sources
PubMed2001

Hypothalamic lesions in multiple sclerosis.

Demyelinating lesions of fiber bundles in and adjacent to the hypothalamus (i.e. the fornix. anterior commissure, internal capsule, and optic system) may be the basis for autonomic and endocrine alterations in multiple sclerosis (MS) patients. Therefore we investigated the presence and immunological activity of lesions in hypothalamic fiber bundles of 17 MS patients and 14 controls. In the MS group, 16 of 17 patients showed demyelinated lesions. The incidence of active lesions was high (60%) and outnumbered chronic inactive lesions in the internal capsule (p = 0.005). In 4 of 17 MS patients, axonal damage was observed and in 3 of 17 MS patients grey matter lesions were apparent. Duration of MS was inversely related to the active hypothalamic MS lesion score (r = -0.72, p = 0.001). Since comparison of hypothalamic lesions with MS lesions in other areas of the brain in the same patients (n = 7) showed a great similarity both as stage and appearance was concerned, this negative relation in all likelihood reflects the clinical consequences of high disease activity throughout the whole brain. In controls no demyelinating lesions were seen but in 11 control cases HLA expression was observed that was lower than that present in MS patients (p = 0.02). In the median eminence region that lacks a blood-brain barrier, all controls showed a strong HLA expression around the blood vessels. We conclude that systematic pathological investigation of the hypothalamus in MS patients reveals an unexpected high incidence of active lesions that may impact on hypothalamic functioning.

Adult↗
PubMed1997

Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions.

The pathology of multiple sclerosis (MS) is characterised by breakdown of the blood-brain barrier accompanied by infiltration of macrophages and T cells into the central nervous system (CNS). Myelin is degraded and engulfed by the macrophages, producing lesions of demyelination. Some or all of these mechanisms might involve proteinases, and here we have studied the cellular localisation and distribution of two matrix metalloproteinases (MMPs), MMP-7 (matrilysin) and MMP-9 (92-kDa gelatinase), in the normal human CNS and active demyelinating MS lesions. Cryostat sections of CNS samples were immunostained with antisera to MMP-7 and MMP-9. In addition, non-radioactive in situ hybridisation (ISH) was performed using a digoxygenin-labelled riboprobe to detect the expression of MMP-7. MMP-7 immunoreactivity was weakly detected in microglial-like cells in normal brain tissue sections, and was very strong in parenchymal macrophages in active demyelinating MS lesions. This pattern of expression was confirmed using ISH. MMP-7 immunoreactivity was not detected in macrophages in spleen or tonsil indicating that it is specifically induced in infiltrating macrophages in active demyelinating MS lesions. MMP-9 immunoreactivity was detected in a few small blood vessels in normal brain tissue sections, whereas many blood vessels stained positive in CNS tissue sections of active demyelinating MS lesions. The up-regulation of MMPs in MS may contribute to the pathology of the disease.

Adult↗
PubMed1997

Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclerosis lesions.

The cellular localization and distribution of inducible and constitutive nitric oxide synthase (iNOS/cNOS) was determined in tissue sections from multiple sclerosis (MS) and control brain and spinal cord. Immunocytochemical techniques were applied using specific iNOS- and cNOS-directed antibodies. In addition, NADPH-diaphorase histochemistry was performed. To establish the identity of iNOS-, cNOS- and NADPH-diaphorase-positive cells single and double staining was performed on tissue sections with the macrophage marker KP1 (CD68) and with the astrocyte marker glial fibrillary acidic protein (GFAP). Areas of myelin breakdown and demyelination were determined using a staining for neutral lipids, Oil Red O (ORO). Furthermore, macrophages isolated from active demyelinating MS lesions were stained for iNOS, cNOS, KP1 and ORO. In active MS lesions strong iNOS immunoreactivity was found exclusively in perivascular and parenchymal macrophages distributed within regions of active demyelination. In these active MS lesions immunoreactivity for cNOS was also found in macrophages. Macrophages isolated from active MS lesions also showed immunoreactivity for iNOS and cNOS. Moreover, these isolated macrophages produced nitric oxide (NO; >30 microM) in vitro. NADPH-diaphorase activity was detected in KP1-positive perivascular and parenchymal macrophages and in GFAP-positive reactive astrocytes in active MS lesions and in reactive astrocytes located in the hypercellular rims of chronic active MS lesions. cNOS-positive reactive astrocytes were detected in both active and chronic active MS lesions. Inside chronic active lesions some residual macrophages were weakly iNOS-positive. In control brain and spinal cord no iNOS immunoreactivity could be detected. These results suggests an important role for human macrophages capable of producing the free radical nitric oxide (NO), which may contribute to the cytotoxicity of oligodendrocytes and destruction of myelin in MS brain and spinal cord.

Aged↗
PubMed1995

Differential expression of the c-kit proto-oncogene in germ cell tumours.

The c-kit proto-oncogene product and its ligand stem cell factor play an important role in haematopoiesis, spermatogenesis, and melanogenesis. Using an anti-c-kit antiserum raised against a synthetic peptide, we studied the immunohistochemical expression of the c-kit gene product in 60 germ cell tumours (GCTs) (53 testicular, 7 extragonadal), derived from primary GCTs in 45 cases and metastatic tumours in 15 cases. Twenty-eight out of 28 seminomas showed c-kit membranous staining in the majority of cells. A similar pattern of expression was seen in intratubular germ cell neoplasia. Nine out of 29 (32 per cent) non-seminomas displayed cytoplasmic, but not membranous, c-kit immunoreactivity in occasional cells. In three mixed GCTs, c-kit expression was limited to the seminoma component. In normal testis, c-kit expression was observed in some basal tubular cells, corresponding to undifferentiated spermatogonia. These results suggest a role for c-kit in the oncogenesis of GCT, where down-regulation of c-kit might be a critical step during progression from seminomas to non-seminomas. Immunohistochemical analysis of c-kit should be considered as a diagnostic aid for GCT and in particular may be helpful in the identification of certain extragonadal seminomas.

Adolescent↗
PubMed1995

Expression of bcl-2 protein and transcription of the Epstein-Barr virus bcl-2 homologue BHRF-1 in Hodgkin's disease: implications for different pathogenic mechanisms.

Epstein-Barr virus (EBV) is frequently found in Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Epstein-Barr virus has transforming properties in vitro and might be involved in the pathogenesis of certain types of Hodgkin's disease. One of the possible mechanisms is the upregulation of the human proto-oncogene bcl-2 by the latent membrane protein 1 of EBV in vitro. Another possibility might be the expression of the viral 'bcl-2 homologue' BHRF-1. In the present study of 64 cases of Hodgkin's disease we investigated the expression of bcl-2 at the protein level in relation to the presence of EBV. Moreover, in 10 EBV positive cases we investigated, the expression of the bcl-2 homologue, BHRF-1, by reverse-transcriptase PCR. bcl-2 was detected in 14 of 22 (64%) EBV positive and in 37 of 42 (88%) EBV negative cases. In 17 of 22 (77%) EBV positive cases Reed-Sternberg cells were negative (n = 8) or expressed the bcl-2 protein in a very low percentage ( < 5%) of cells (n = 9), whereas in 20 of 42 (43%) of the EBV negative cases the majority ( > 50%) of the neoplastic cells were bcl-2 positive. Using the reverse-transcriptase PCR with primers amplifying transcripts of BHRF-1 we were able to detect BHRF-1 transcripts in only one of the 10 tested cases of EBV positive Hodgkin's disease. Our data indicate that in EBV positive Hodgkin's disease growth advantage of Reed-Sternberg cells is not obtained by upregulation of bcl-2 or by the EBV homologue BHRF-1.

Base Sequence↗
PubMed1995

Distribution of extracellular matrix components and their receptors in human lymphoid tissue and B-cell non-Hodgkin lymphomas.

In this study the distribution patterns of various extracellular matrix components and their receptors (i.e. beta 1 integrins) in B-cell non-Hodgkin lymphomas were examined and compared to those in reactive lymphoid tissue. Neoplastic follicles within follicular lymphomas showed similar patterns to that observed in reactive follicles, which appeared to be strongly associated with the presence of follicular dendritic cells. Diffuse lymphomas of low and intermediate malignancy grade revealed features comparable to those of interfollicular areas of reactive lymphoid tissue, irrespective to which compartment the tumour cells were related. Highly malignant lymphomas, however, displayed unique extracellular matrix configurations, resulting from active matrix degradation by macrophages; this may support rapid tumour growth. Extranodal lymphomas showed virtually the same matrix patterns as their nodal counterparts, suggesting that (malignant) lymphoid cells generate (at least partly) their own specific microenvironment. In reactive lymphoid tissue beta 1 integrins were mainly found on resident cells and except for alpha 4, alpha 5 (and beta 1) the lymphoid cells expressed very little, if any, beta 1 integrins. In comparison, expression of these integrins on lymphoma cells was reduced (follicular lymphomas) or could not be detected at all (diffusely growing lymphomas); this might contribute to the growth pattern and metastatic properties of the tumours.

Cell Adhesion Molecules, Neuronal↗
PubMed1994

Decreased expression of cellular markers in Epstein-Barr virus-positive Hodgkin's disease.

Epstein-Barr virus (EBV) has been demonstrated in the Reed-Sternberg cells and their mononuclear variants (Hodgkin cells; H-RS cells) in a substantial number of Hodgkin's disease (HD) cases. Moreover, EBV can modulate both in vivo and in vitro the expression of several cellular genes, including lymphoid differentiation markers. Therefore we investigated, in 64 cases of HD, the relationship between the presence of EBV and the expression of lymphoid (CD45RB), T- (CD3, CD45RO), B- (CD20, MB2 antigen, CDw75), and myeloid-cell lineage markers (CD15), and of activation markers (CD30, EMA, and the 115D8 antigen) on the H-RS cells. EBV-positive cases, as demonstrated by the presence of EBER-1 and -2 RNA and LMP-1 protein expression, showed a significant reduction in the expression on H-RS cells of T-cell lineage (CD3, P < 0.02), B-cell lineage (CD20; P < 0.005), and activation markers (EMA; P < 0.002 and the 115D8 antigen; P < 0.001) as compared with EBV-negative cases. No differences were found in the expression of CD15, CD30, CD45RO, CD45RB, CDw75, or the MB2 antigen on H-RS cells in EBV-positive and EBV-negative HD cases. Interestingly, in 11 cases of EBV-negative HD, B- as well as T-cell lineage markers could be found on some H-RS cells. These data suggest that EBV in H-RS cells is able to down-regulate the expression of T- (CD3) and B- (CD20) cell lineage markers and lymphoid activation markers (EMA and the 115D8 antigen).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1993

Primary malignant lymphoma of the uterus: localization in a cervical polyp.

Distinction between benign and malignant lymphoid lesions of the uterine cervix can be difficult. Two patients showing atypical lymphoid tissue confined to a uterine cervical polyp are presented. In one patient a non-Hodgkin lymphoma stage IE was diagnosed. Treatment consisted of combination chemotherapy. In a second patient the lesion was classified as atypical lymphoid hyperplasia. No treatment was initiated. The presence of a non-Hodgkin lymphoma in a cervical polyp is extremely rare. Distinction between benign and malignant lymphoid tissue within a cervical polyp can be facilitated by immunohistochemical staining and application of the histological criteria for a reactive nature of such lesions.

Adult↗
PubMed1993

Detection of Epstein-Barr virus nucleic acid sequences and protein in nodal T-cell lymphomas: relation between latent membrane protein-1 positivity and clinical course.

Forty-six nodal T-cell lymphomas, classified according to the updated Kiel classification, were investigated for the presence of Epstein-Barr virus (EBV) DNA by polymerase chain reaction (PCR), EBER 1 and 2 (EBER 1/2) and latent membrane protein-1 (LMP-1) expression. A combination of RNA in situ hybridization and immunohistochemistry was used to establish the phenotype of the Epstein-Barr virus harbouring cells. In 21 of 45 cases Epstein-Barr virus DNA sequences could be detected with the polymerase chain reaction. In 15 cases (14 of 21 EBV PCR positive cases), EBER 1/2 positive cells could be demonstrated. As judged by morphology, EBER 1/2 expression was found in nonneoplastic and neoplastic lymphoid cells. Double staining revealed that more than 80% of the EBER 1/2 harbouring cells, lacked B-, T- or histiocytic markers, suggesting down regulation of T- and B-cell markers by Epstein-Barr virus. In eight of 15 cases some EBER 1/2 positive T-cells (CD3, CD45RO, CD43) morphologically resembling tumour cells were found. In nine of 14 cases tested EBER 1/2 positive non-neoplastic B-cells (CD20) were seen. Based on in situ hybridization results, four patterns of EBER 1/2 positive cells were found, i.e. single cells (< 1 per medium power field (mpf), n = 3), scattered (1-25/mpf, n = 4), clustered (26-100/mpf, n = 5) and diffuse (> 100/mpf, n = 3). In eight of 15 cases a clustered or diffuse pattern of EBER 1/2 positive cells was found and these lymphomas were therefore considered to be strongly associated with Epstein-Barr virus. In these lymphomas LMP-1 expression was found to be associated with an aggressive clinical course and hepatosplenomegaly.

Herpesvirus 4, Human↗
PubMed1992

MR imaging of skeletal metastases from medulloblastoma.

The findings of MR imaging in 3 patients with bone metastases from medulloblastoma are reported. The first patient showed focal lesions of low signal intensity on T1-weighted spin echo images at a time when bone scintigraphy was negative for metastases. This patient later developed extensive osteosclerotic lesions visible on plain films. The bone marrow of the second patient showed diffuse low signal intensity on T1-weighted images. After chemotherapy the signal intensity of the bone marrow increased which correlated with a return of normal hematopoietic tissue. A response to chemotherapy was also found on MR imaging and repeat bone marrow biopsies in a third patient. A consistent finding was a low signal intensity on pre-gadolinium images, but the pattern (focal or diffuse abnormal signal intensity) was different in each patient. To our knowledge, this is the first report on MR imaging findings in bone metastases from medulloblastoma.

Acetabulum↗
PubMed1992

Epstein-Barr virus DNA in Reed-Sternberg cells of Hodgkin's disease is frequently associated with CR2 (EBV receptor) expression.

We studied 44 cases of Hodgkin's disease for the presence of Epstein-Barr virus (EBV) DNA, its localization and the expression of the EBV receptor on the tumour cells. EBV DNA was found in 52% (16/31) of the Hodgkin's lymphomas using the polymerase chain reaction. With a very sensitive non-radioactive DNA in situ hybridization technique in combination with immunohistochemistry for CD 30 or CD 15 antigens, EBV DNA was localized to Reed-Sternberg cells and its mononuclear variants. The relationship between the presence of EBV DNA and the expression of the EBV-receptor CR2 (CD 21) on Reed-Sternberg cells was studied using the same techniques and two different monoclonal anti-CD 21 antibodies. CR2 could be detected on a substantial number of the Reed-Sternberg cells in EBV DNA positive Hodgkin's lymphomas (9/12; 75%), whereas in EBV negative cases positivity with anti-CD 21 was rare (1/13; 8%). The results indicate that CR2 expression on Reed-Sternberg cells and the presence of EBV DNA sequences are frequently associated in Hodgkin's lymphomas.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Small cell carcinoma of the urinary bladder. A clinicopathologic, morphometric, immunohistochemical, and ultrastructural study of 18 cases.

A multiinstitutional review of 3778 patients with a primary malignancy of the urinary bladder revealed 18 cases (0.48%) of small cell carcinoma which were histologically and morphometrically identical to pulmonary small cell undifferentiated carcinoma. Age, sex, and symptoms at first presentation were comparable to that known in transitional cell carcinoma. Sixteen patients (89%) developed metastatic disease, with most frequent involvement of regional lymph nodes, liver, skeleton, and abdominal cavity. The unfavorable clinical outcome was worse as compared with that reported in advanced stage poorly differentiated transitional cell carcinoma, and was similar to the rapidly fatal outcome of pulmonary small cell undifferentiated carcinoma. Fourteen patients (78%) died by tumor at a mean follow-up period of 9.4 months, and only one patient was free of recurrent disease more than 5 years after cystectomy. This apparent aggressive tumor behavior was independent of the presence of neuroendocrine differentiation characteristics at immunohistochemical (13 cases, 72%) or electron microscopic study (eight cases, 44%). The prolonged survival periods (15-38 months) of the five patients who received combination chemotherapy suggested that, just as in small cell lung carcinoma, chemotherapy may be profitable. A unified concept of histogenesis of bladder cancer with a common origin from a multipotent mucosal stem cell is proposed.

Aged↗
PubMed1988

The non-Hodgkin's lymphomas: old and new thinking.

Knowledge of non-Hodgkin's lymphomas has increased enormously in the last 10-15 years. The various types are considered to reflect the normal immunological processes that take place in the lymphoid tissue after antigenic challenge. This concept, which states that non-Hodgkin's lymphomas are neoplastic counterparts of normal processes, has implications for morphology, immunology and clinical behaviour. Based on this concept, as well as on immunohistological and functional data, a hypothetical scheme of B-cell development is proposed. The relation to normal physiology also holds for lymphomas localized outside the lymph nodes. Normal structure and function in two important extranodal lymphoid tissues, the gastrointestinal mucosa and the skin-associated lymphoid tissues, are related to the lymphomas arising in these sites. This relation and some of its implications are discussed, with special reference to the important processes of homing and recirculation of lymphocytes.

B-Lymphocytes↗
PubMed1985

Some characteristics of hyperoxia-adapted HeLa cells. A tissue culture model for cellular oxygen tolerance.

By culturing HeLa cells at stepwise increased oxygen tensions over a prolonged period of time (approximately 21 months) we selected a substrain capable of growing under 80% O2/19% N2/1% CO2, an oxygen level that is lethal to normal HeLa cells, adapted to 20% O2/79% N2/1% CO2. The 80% O2-adapted cells exhibited the following characteristics. At the ultrastructural level an abnormal mitochondrial morphology was observed: compared to normal cells, mitochondria of the hyperoxia-adapted cells exhibited a 3-fold larger mean profile area in sections and were slightly decreased in number; the relative mitochondrial volume was increased 2-fold, whereas the size of both cell types was the same. Mitochondrial matrix appeared less dense in the hyperoxia-adapted cells; no structural damage was detected. Compared to the 20% O2-adapted cells O2 consumption per cell was approximately 40% decreased in the 80% O2-adapted cells. Under hyperoxic conditions 20% O2-adapted and 80% O2-adapted cells exhibited very similar cyanide-resistant respiration rates (0.16 +/- 0.04 and 0.15 +/- 0.02 fmoles/cell/minute, respectively), suggesting that the increased O2 tolerance of the 80% O2-adapted cells was not due to a decreased cellular production of activated oxygen species at hyperoxia. Cellular levels of the enzymes directly involved in protection against activated oxygen species, i.e., superoxide dismutases, catalase, and glutathione peroxidase, were normal or slightly below normal in the 80% O2-adapted cells, implying that these enzymes were of no significance for the increased O2 tolerance. In addition, the specific activity of glucose-6-phosphate dehydrogenase, a key enzyme for cellular production of NADPH, was not related to the degree of O2 tolerance. Our results suggest that the increased O2 tolerance of the 80% O2-adapted cells is neither based on cellular properties controlling the formation or removal of intracellular activated oxygen species nor on the cellular capacity to repair or replace damaged cellular components. We speculate that the increased O2 tolerance is largely due to a genetically determined increased resistance of oxygen-sensitive cellular targets.

DNA↗
PubMed1984

Immunohistochemical studies of the spleen in hairy-cell leukemia.

Immunohistochemical studies of 10 spleens from patients with hairy-cell leukemia (HCL) with a battery of monoclonal and heterologous antibodies were performed in order to obtain information on the phenotype of the neoplastic cells and the admixture of reactive cells. The hairy cells (HCs) were shown to react with several anti-B-cell antibodies (Y29/55, Leu10, HLA-DR), but only a minority of cases showed reactivity with antibody BA-1. The cells of all cases were nonreactive with anti-T and/or anti-macrophage antibodies. In contrast with cell-suspension studies, in immunohistochemical studies the HCs did not react with antibody OKM1. The reactive T-lymphocytes showed a shift toward T helper cells in the red pulp, but not in the white pulp. It was confirmed that "pseudosinuses" and "bloodlakes" are outlined by HCs and not by sinus-lining cells: the lining cells of the blood lakes were Y29/55+ and Leu10+, but negative with antibodies known to react with sinus-lining cells (Leu2a, BA-2). These data suggest that immunohistologic studies of the spleen in patients with HCL can be helpful in differential diagnosis and can provide information concerning the reaction of splenic tissue to the infiltration by hairy cells.

Antibodies, Monoclonal↗
PubMed1982

Dendritic reticulum cell sarcoma? Four cases of a lymphoma probably derived from dendritic reticulum cells of the follicular compartment.

This paper describes the histological picture of four tumours of the follicular compartment of the lymph node, in which the proliferating cell appeared to be the dendritic reticulum cell (DRC). This assumption was based on the results of light microscopical, ultrastructural, immunological, and enzymehistochemical investigations. The tumour cells resembled DRC's closely in (1) the striking pattern of interdigitations and occasional tight junction-like contacts between the neoplastic cells on electron microscopical analysis; (2) presence of receptors for the activated third component of complement on the membrane of the cells; (3) absence of monoclonal immunoglobulins and T-cell antigen on the surface and of lysozyme, alpha 1-antitrypsin or alpha 1-antichymotrypsin in the cytoplasm of the neoplastic cells. Moreover, (4) the tumour cells showed moderate alpha-naphtyl acetate esterase, weak to absent acid phosphatase and (with one exception) strong 5-nucleotidase activity. Furthermore, (5) the neoplastic cells expressed Ia-like antigens on the surface in all four cases. The relation with follicle centre cell lymphomas, the differential diagnosis and clinical data are discussed.

Adult↗