Biomedical subjects

F J van Kemenade

Publications and source records attributed to F J van Kemenade.

15 recordsLinked to original sources

PubMed2006

Implementation of human papillomavirus testing in cervical screening without a concomitant decrease in participation rate.

Adding high-risk human papillomavirus (hrHPV) testing to screening increases the efficacy of cervical screening programmes. However, hrHPV testing may result in a lower participation rate because of the perceived association with sexually transmitted infections. We describe how testing for hrHPV was added to cervical screening in the POpulation-BAsed SCreening study AMsterdam (POBASCAM) trial. Participation rates of the screening programme before and after hrHPV implementation were evaluated in the region where the POBASCAM trial was carried out. The participation rate was 58.7% before and 61.4% after the addition of hrHPV testing to screening (p<0.001). An inventory of frequently asked questions is presented. Thus, hrHPV testing can be added to cervical screening by cytology without a decrease in participation rate.

Adult↗

PubMed2006

Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands.

We present the type-distribution of high-risk human papillomavirus (HPV) types in women with normal cytology (n=1467), adenocarcinoma in situ (ACIS) (n=61), adenocarcinoma (n=70), and squamous cell carcinoma (SCC) (n=83). Cervical adenocarcinoma and ACIS were significantly more frequently associated with HPV18 (OR(MH) 15.0; 95% CI 8.6-26.1 and 21.8; 95% CI 11.9-39.8, respectively) than normal cytology. Human papillomavirus16 was only associated with adenocarcinoma and ACIS after exclusion of HPV18-positive cases (OR(MH) 6.6; 95% CI 2.8-16.0 and 9.4; 95% CI 2.8-31.2, respectively). For SCC, HPV16 prevalence was elevated (OR(MH) 7.0; 95% CI 3.9-12.4) compared to cases with normal cytology, and HPV18 prevalence was only increased after exclusion of HPV16-positive cases (OR(MH) 4.3; 95% CI 1.6-11.6). These results suggest that HPV18 is mainly a risk factor for the development of adenocarcinoma whereas HPV16 is associated with both SCC and adenocarcinoma.

Adenocarcinoma↗

PubMed2004

HPV testing and monitoring of women after treatment of CIN 3: review of the literature and meta-analysis.

According to the current guidelines in most western countries, women treated for cervical intraepithelial neoplasia grade 3 (CIN 3) are followed for at least 2 years after treatment by cytology.High-risk human papillomavirus (hrHPV) infections are necessary for the development and maintenance of CIN 3. HrHPV testing could be used to improve monitoring of women treated for CIN 3. This has prompted numerous studies for the implementation of hrHPV testing in monitoring of women treated for CIN 3. Included in this review are 20 studies, published between 1996 and 2003, comparing hrHPV testing with either resection margins or cervical cytology to predict recurrent/residual disease, and 11 of them could be used in a meta-analysis. In the meta-analysis of the 11 studies, the negative predictive value (NPV) for recurrent/residual disease of hrHPV testing was 98% (95% CI 97-99%), that of resection margins 91% (95% CI 87-94%), and that of cervical cytology 93% (95% CI 90-95%). When hrHPV testing was performed in conjunction with cytology, the sensitivity was 96% (95% CI 89-99%), specificity was 81% (95% CI 77-84%), the associated positive predictive value (PPV) was 46% (95% CI 38-54%), and the NPV was 99% (95% CI 98-100%). Combined hrHPV and cytology testing yielded the best test characteristics. We propose to include hrHPV testing in conjunction with cytology for monitoring women treated for CIN 3. Some follow-up visits for women testing negative for both hrHPV and cytology can be skipped. In western countries, this could mean that for women double negative at 6 months, retesting at 12 months should be skipped while keeping the 24-month follow-up visit.

Cervix Uteri↗

PubMed2003

[Sarcoidosis: immunopathogenesis and the potential of immunotherapy].

Sarcoidosis is a multi-systemic disease of unknown aetiology, immunopathologically and histologically characterised by a macrophage/T-helper I cell-mediated non-caseating granulomatous inflammation process. In the development of granulomas, an imbalance between pro-inflammatory and anti-inflammatory cytokines plays an important role, possibly initiated by an as yet unidentified (exogenous) stimulus. The clinical outcome of the disease process is unpredictable, and appears to be determined by the cytokine production of the inflammatory cells in the granuloma. Fifty to seventy percent of the patients recover without medication within a period of time which cannot be predicted, the other 30 to 50% of patients are treated during the course of the disease with corticosteroids (with varying degrees of success), either alone or in combination with cytostatic or immunosuppressive agents. Based on recent developments in the field of immunomodulation and on current knowledge of the immunopathogenesis of sarcoidosis, there appear to be opportunities for specific immunotherapy which should be evaluated in controlled studies.

Anti-Inflammatory Agents↗

PubMed2001

Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma.

Polycomb-group (PcG) proteins, such as BMI-1 and EZH2, form multimeric gene-repressing complexes involved in axial patterning, hematopoiesis, and cell cycle regulation. In addition, BMI-1 is involved in experimental lymphomagenesis. Little is known about its role in human lymphomagenesis. Here, BMI-1 and EZH2 expression patterns are analyzed in a variety of B-cell non-Hodgkin lymphomas (B-NHLs), including small lymphocytic lymphoma, follicular lymphoma, large B-cell lymphoma, mantle-cell lymphoma, and Burkitt lymphoma. In contrast to the mutually exclusive pattern of BMI-1 and EZH2 in reactive follicles, the neoplastic cells in B-NHLs of intermediate- and high-grade malignancy showed strong coexpression of BMI-1 and EZH2. This pattern overlapped with the expression of Mib-1/Ki-67, a marker for proliferation. Neoplastic cells in B-NHL of low-grade malignancy were either BMI-1(low)/EZH2(+) (neoplastic centroblasts) or BMI-1(low)EZH2(-) (neoplastic centrocytes). These observations show that low-, intermediate-, and high grade B-NHLs are associated with increased coexpression of the BMI-1 and EZH2 PcG proteins, whose normal expression pattern is mutually exclusive. This expression pattern is probably caused by a failure to down-regulate BMI-1 in dividing neoplastic cells, because BMI-1 expression is absent from normal dividing B cells. These observations are in agreement with findings in studies of Bmi-1 transgenic mice. The extent of BMI-1/EZH2 coexpression correlated with clinical grade and the presence of Mib-1/Ki-67 expression, suggesting that the irregular expression of BMI-1 and EZH2 is an early event in the formation of B-NHL. This points to a role for abnormal PcG expression in human lymphomagenesis. (Blood. 2001;97:3896-3901)

Adolescent↗

PubMed2001

Distinct BMI-1 and EZH2 expression patterns in thymocytes and mature T cells suggest a role for Polycomb genes in human T cell differentiation.

BMI-1 and EZH2 Polycomb-group (PcG) proteins belong to two distinct protein complexes involved in the regulation of hematopoiesis. Using unique PcG-specific antisera and triple immunofluorescence, we found that mature resting peripheral T cells expressed BMI-1, whereas dividing blasts were EZH2(+). By contrast, subcapsular immature double-negative (DN) (CD4(-)/CD8(-)) T cells in the thymus coexpressed BMI-1 and EZH2 or were BMI-1 single positive. Their descendants, double-positive (DP; CD4(+)/CD8(+)) cortical thymocytes, expressed EZH2 without BMI-1. Most EZH2(+) DN and DP thymocytes were dividing, while DN BMI-1(+)/EZH2(-) thymocytes were resting and proliferation was occasionally noted in DN BMI-1(+)/EZH2(+) cells. Maturation of DP cortical thymocytes to single-positive (CD4(+)/CD8(-) or CD8(+)/CD4(-)) medullar thymocytes correlated with decreased detectability of EZH2 and continued relative absence of BMI-1. Our data show that BMI-1 and EZH2 expression in mature peripheral T cells is mutually exclusive and linked to proliferation status, and that this pattern is not yet established in thymocytes of the cortex and medulla. T cell stage-specific PcG expression profiles suggest that PcG genes contribute to regulation of T cell differentiation. They probably reflect stabilization of cell type-specific gene expression and irreversibility of lineage choice. The difference in PcG expression between medullar thymocytes and mature interfollicular T cells indicates that additional maturation processes occur after thymocyte transportation from the thymus.

CD4-Positive T-Lymphocytes↗

PubMed2001

Endothelial cell chimerism after renal transplantation and vascular rejection.

BACKGROUND: The blood vessels of a transplanted organ are the interface between donor and recipient. The endothelium in the blood vessels is thought to be the major target for graft rejection. Endothelial cells of a transplanted organ are believed to remain of donor origin after transplantation. We aimed to verify this concept. METHODS: We studied biopsy samples from 12 renal transplants for the presence of endothelial cells of recipient origin. We used three different techniques: immunohistochemistry for MHC class-I antigens, immunohistochemistry for ABO-blood-group antigens, and in-situ hybridisation for X and Y chromosomes. After we had confirmed that these techniques did identify endothelial cells of recipient origin, tests were done in a second group of 26 patients to find out whether endothelial chimerism correlated with graft rejection. FINDINGS: We found a strong correlation between the percentage of recipient endothelial cells in the peritubular capillaries and the type of graft rejection (r = 0.71, p < 0.0001). These cells were found mainly in grafts of patients who had had rejection, especially among patients with vascular rejection. In grafts of patients without rejection only sporadically recipient endothelial cells were detectable. INTERPRETATION: Our data show that endothelial cells of the recipient can replace those of the donor. This replacement is associated with graft rejection. We postulate that endothelium that is damaged by vascular rejection is repaired by endothelial cells of the recipient.

ABO Blood-Group System↗

PubMed2001

Low arginine plasma levels do not aggravate renal blood flow after experimental renal ischaemia/reperfusion.

BACKGROUND: Ischaemic renal dysfunction is present in many clinical settings, including cardiovascular surgery. Renal hypoperfusion seems to be the most important pathophysiologic mechanism. Arginine plasma levels are rate limiting for NO synthesis, and low arginine plasma levels are seen after major vascular surgery. OBJECTIVE: to establish the effects of low arginine plasma levels on renal blood flow after renal ischaemia/reperfusion. DESIGN: Wistar rats were used in this unilateral renal ischaemia/reperfusion model. After 70 min of ischaemia, the kidney was reperfused for 150 min. Arginase infusion was used to lower arginine plasma levels. Blood flow measurement was performed at the end of the experiment using radiolabelled microspheres. Additional experiments were performed for histopathology. RESULTS: Arginase efficiently decreased arginine plasma levels to about 50% of normal. There was a lower blood flow in the ischaemic kidney than the contralateral (non-ischaemic) kidney. Lowering arginine plasma levels did not reduce renal blood flow in the ischaemic kidney. Renal histopathology was not influenced by lowered arginine plasma levels. CONCLUSIONS: Lowering arginine plasma levels did not affect blood flow or histology following renal ischaemia and reperfusion.

Animals↗

PubMed2000

Cutting edge: polycomb gene expression patterns reflect distinct B cell differentiation stages in human germinal centers.

Polycomb group (Pc-G) proteins regulate homeotic gene expression in Drosophila, mouse, and humans. Mouse Pc-G proteins are also essential for adult hematopoietic development and contribute to cell cycle regulation. We show that human Pc-G expression patterns correlate with different B cell differentiation stages and that they reflect germinal center (GC) architecture. The transition of resting mantle B cells to rapidly dividing Mib-1(Ki-67)+ follicular centroblasts coincides with loss of BMI-1 and RING1 Pc-G protein detection and appearance of ENX and EED Pc-G protein expression. By contrast, differentiation of centroblasts into centrocytes correlates with reappearance of BMI-1/RING1 and loss of ENX/EED and Mib-1 expression. The mutually exclusive expression of ENX/EED and BMI-1/RING1 reflects the differential composition of two distinct Pc-G complexes. The Pc-G expression profiles in various GC B cell differentiation stages suggest a role for Pc-G proteins in GC development.

B-Lymphocyte Subsets↗

PubMed2000

Coexpression of BMI-1 and EZH2 polycomb group genes in Reed-Sternberg cells of Hodgkin's disease.

The human BMI-1 and EZH2 polycomb group (PcG) proteins are constituents of two distinct complexes of PcG proteins with gene regulatory activity. PcG proteins ensure correct embryonic development by suppressing homeobox genes, and they also contribute to regulation of lymphopoiesis. The two PcG complexes are thought to regulate different target genes and probably have different tissue distributions. Altered expression of PcG genes is linked to transformation in cell lines and induction of tumors in mutant mice, but the role of PcG genes in human cancers is relatively unexplored. Using antisera specific for human PcG proteins, we used immunohistochemistry and immunofluorescence to detect BMI-1 and EZH2 PcG proteins in Reed-Sternberg cells of Hodgkin's disease (HRS). The expression patterns were compared to those in follicular lymphocytes of the lymph node, the normal counterparts of HRS cells. In the germinal center, expression of BMI-1 is restricted to resting Mib-1/Ki-67(-) centrocytes, whereas EZH2 expression is associated with dividing Mib-1/Ki-67(+) centroblasts. By contrast, HRS cells coexpress BMI-1, EZH2, and Mib-1/Ki-67. Because HRS cells are thought to originate from germinal center lymphocytes, these observations suggests that Hodgkin's disease is associated with coexpression of BMI-1 and EZH2 in HRS cells.

Adolescent↗

PubMed1999

Sharing cross-reactive groups of MHC class I improves long-term graft survival.

BACKGROUND: Renal transplant loss from chronic rejection remains substantial. To increase our understanding of this syndrome, we identified risk factors predicting late graft loss, with a special emphasis on the impact of human lymphocyte antigen (HLA) matching. METHODS: We studied all 654 cadaveric kidney transplants performed in our center between 1983 and 1996 that had survived for more than six months. Eighty-two transplants, lost because of chronic rejection, were used as the outcome variable. The influence of HLA mismatches and shares on long-term graft survival was evaluated at the level of private antigens and cross-reactive groups (CREG) of multiple histocompatibility complex (MHC) class I. HLA and other recipient, donors and transplant parameters were studied using univariate and multivariate Cox regression analysis. RESULTS: The cohort had a mean number of 1.9 HLA mismatches. Because of the homozygosity of HLA antigens, HLA mismatches were not reciprocal to shares. CREG and HLA-A-B mismatches had a relative risk for graft loss of 1.19 (95% CI, 0.97 to 1.45) and 1.05 (0.84 to 1.32) per mismatch. In contrast, the relative risk per shared CREG and broad HLA-A-B antigen was 0.76 (0.63 to 0.92) and 0.79 (0.61 to 1.03). Multivariate analysis revealed that individuals sharing less than four CREGs had a relative risk of 2.13 (1.29 to 3.75) for late graft loss. Other independent predictors were a recipient age of less than 50 years, relative risk 1.95 (1.02 to 3.71); a donor age of more than 50 years, relative risk 1.68 (1.01 to 2.80); acute rejection (vascular vs. no rejection), relative risk 3.52 (1.72 to 7.18); proteinuria (dipstick > 1+ vs. negative), relative risk 2.86 (1.29 to 6.35); and a serum creatinine concentration of more than 150 micromol/liter at six months, relative risk 3.41 (1.96 to 5.94). CONCLUSION: We identified several coexisting recipient-, donor-, and transplant-related risk factors for graft loss from chronic rejection. In this well-matched group of renal transplants, HLA mismatches and shares had a nonreciprocal relationship. Sharing of HLA antigens, especially CREG of MHC class I, was associated with improved long-term survival.

Adult↗

PubMed1994

Simultaneous regulation of CD2 adhesion and signaling functions by a novel CD2 monoclonal antibody.

Accessory molecules on T cells can support adhesion and transduce agonistic signals that facilitate Ag receptor-induced T cell activation. The T cell differentiation Ag CD2 may exert both functions, as has been amply demonstrated in studies with CD2 mAbs. In addition, experiments in which either purified ligand (CD58) or transfected CD2 and CD58 molecules were used have confirmed this notion. However, controversy exists as to whether CD2 alters its affinity for CD58 in the course of T cell stimulation, and whether this putative affinity change affects CD2-mediated activation signals. We now describe a CD2 mAb (HIK27) that recognizes an epitope constitutively expressed on resting T cells and induces increased adhesiveness of CD2 toward CD58. Addition of HIK27 to a stimulatory but nonmitogenic pair of CD2 mAbs induces a strong proliferative response. Finally, HIK27 was found to be co-mitogenic with CD58 expressed on sheep erythrocytes, B cell lines, and CD58-transfected L cells. The simultaneous modulation of CD2 adhesion and signaling on HIK27 binding suggests that both functions of the molecule may be enhanced in the course of T cell stimulation.

Animals↗

PubMed1994

Glucosidase trimming inhibitors preferentially perturb T cell activation induced by CD2 mAb.

Glycosidase trimming inhibitors may be used to study contribution of N-linked glycan moieties in T cell function. We have studied the effects of castanospermine (Cas), swainsonine (Swain), 1-deoxynojirimycin (dNM), and 1-deoxymannojirimycin (dMM) on T cell activation and differentiation. Our analysis included a new dNM derivative, N-pentyl-1-deoxynojirimycin (pentyldNM). Previous reports showed inhibitory action of trimming inhibitors, such as Swain and Cas, on pokeweed mitogen-driven immunoglobulin (Ig) production. We extend these findings for pentyldNM and observed that glucosidase inhibitors, Cas and pentyldNM were effective in inhibiting CD2 and CD3 monoclonal antibody (mAb) driven Ig production. The pattern of inhibition by mannosidase and glucosidase inhibitors correlated with inhibitory action on T cell activation: only glucosidase trimming inhibitors (Cas and pentyldNM with comparable potency) perturbed mAb-induced T cell activation, in particular if induced by CD2 mAb. Expression of the early activation marker CD69 was not decreased in the presence of these inhibitors, while addition of exogenous recombinant interleukin-2 partially overcame inhibitory effects during proliferation. These findings suggest that glucosidase, but not mannosidase, trimming inhibitors interfere with a late phase of T cell activation. In addition, the enhanced sensitivity of CD2 mAb-induced proliferation for glucosidase trimming inhibitors suggests dependence on N-linked glycans during CD2-mediated adhesion and triggering functions.

1-Deoxynojirimycin↗

PubMed1993

Skewing to the LFA-3 adhesion pathway by influenza infection of antigen-presenting cells.

The effect of influenza (FLU) infection on heterotypic conjugate formation between antigen-presenting cells and T lymphocytes has been studied with FLU-specific T cell clones and FLU-infected B-lymphoblastoid cells (B-LCL). Conjugate formation between FLU-infected B-LCL (FLU+ B-LCL) and T cells was found to be consistently enhanced in comparison with peptide-sensitized or uninfected B-LCL. Treatment of B-LCL with exogenous neuraminidase (NA-NAse) similarly enhanced conjugate formation indicating that increased conjugate formation may be mediated by the viral neuraminidase. Monoclonal antibody blocking experiments revealed that the contribution by CD2/LFA-3 is increased relative to that of LFA-1/ICAM-1 in conjugates between FLU+ B-LCL or NANAse-treated B-LCL and T cell clones. In contrast, both pathways of adhesion contributed equally to conjugate formation between peptide-sensitized B-LCL or control B-LCL and T cell clones. Thus, FLU infection causes increased conjugate formation between antigen-presenting cells and T cells and skews towards CD2/LFA-3-dependent adhesion, independent of T cell receptor signalling.

Antigen-Presenting Cells↗

PubMed1992

HLA class I and II molecules present influenza virus antigens with different kinetics.

Human leukocyte antigen (HLA) class I and class II molecules differ with respect to their intracellular pathways and the compartments where they associate with processed antigen. To study possible consequences of these differences for the kinetics of antigen presentation by HLA class I and class II molecules, we analyzed changes in the concentrations of free intracellular calcium ions in influenza virus-specific T cell clones after recognition of specific antigen/HLA complexes. HLA class II-restricted viral antigen presentation by Epstein-Barr virus-transformed B lymphoblastoid cell lines (B-LCL) to CD4+ T cell clones started within 1 h and showed little variability, irrespective of antigen specificity or restriction element tested. In contrast, kinetics of viral antigen presentation by HLA class I molecules to CD8+ T cell clones were slower and differed for three antigen/HLA class I complexes tested. While B-LCL presented antigen by HLA-A2 and by HLA-B37 after at least 2 h, they only started to present antigen in the context of HLA-B7 after more than 4 h. This difference in kinetics did not correlate with differences in bulk transport rates of HLA-A2, HLA-B37, and HLA-B7, but seemed greatly influenced by differential rates of peptide generation. Brefeldin A treatment of B-LCL showed for both HLA class I and class II that de novo synthesized HLA molecules were involved in antigen presentation. Thus, differences between intracellular pathways of HLA class I and class II molecules may result in different kinetics of antigen presentation.

Antigens, Viral↗