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C J Meijer

Publications and source records attributed to C J Meijer.

At least 19 recordsLinked to original sources
PubMed1996

Transition of human papillomavirus type 16 and 18 transfected human foreskin keratinocytes towards immortality: activation of telomerase and allele losses at 3p, 10p, 11q and/or 18q.

This study aimed at resolving cellular genetic alterations in the process of in vitro immortalization of human keratinocytes by human papillomavirus (HPV) types 16 and 18. Four cell lines of primary human foreskin keratinocytes transfected with HPV 16 and HPV 18, respectively, were analysed during the transition from the mortal to immortal state. All cell lines showed strong telomerase activity at the immortal state, whereas no or only weak telomerase activity was detected in mortal precursor cells. This was consistent with telomere stabilization or restoration only observed in immortal cells. HPV physical state and copy number appeared constant during immortalization and HPV E6/E7 transcripts were present throughout. Immortalization was associated with clonal allele losses at 3p combined with either 11q or 18q or at 10p, dependent on the cell line. Moreover, a correlation was evident between the onset of telomerase activity and allele loss at 3p or 10p. All immortalized cells retained the capability to differentiate after growth in the presence of physiological calcium and serum. Moreover, one of the immortal cell lines displayed terminal differentiation after organotypic culturing on collagen rafts. The data suggest that (a) several pathways exist for HPV mediated immortalization that may involve genes residing at 3p, 10p, 11q and/or 18q; (b) 3p and 10p may encode genes involved in telomerase regulation; and (c) immortalization in vitro can be correlated with a spectrum of morphological changes varying from mild to severe dysplasia.

Alleles↗
PubMed1996

Prevalence of mucosotropic human papillomaviruses in squamous-cell carcinoma of the head and neck.

The prevalence of mucosotropic human papillomavirus (HPV) DNA in 63 squamous-cell carcinomas (SCC) from different anatomic sites in the head and neck was determined by general primer-mediated polymerase chain reaction (GP-PCR). HPV DNA was detected in 20.6% of SCC. Additional type-specific PCR for HPV 6, 11, 16, 18, 31 and 33 demonstrated the presence of HPV 16 alone in these carcinomas. HPV 16 was also detected in normal epithelium from the resection margins of the majority of HPV-positive SCC. HPV status did not correlate with tumour site, whether primary or recurrent, TNM stage, metastases, degree of differentiation, smoking or alcohol history, fate or survival.

Alcohol Drinking↗
PubMed1996

Analysis of major histocompatibility complex class I expression on Reed-Sternberg cells in relation to the cytotoxic T-cell response in Epstein-Barr virus-positive and -negative Hodgkin's disease.

To get insight into the failure of the immune system to eradicate Epstein-Barr virus (EBV) harboring Hodgkin and Reed-Sternberg cells (H-RS cells), expressing the latent membrane protein 1 (LMP1), we analyzed major histocompatibility complex (MHC) class I expression on H-RS cells in relation to the presence of activated cytotoxic cells, i.e., granzyme-B-expressing lymphocytes. H-RS cells in EBV+ cases of Hodgkin's disease (HD) were found to express significantly higher levels of MCH class I heavy- and light-chain molecules compared with EBV- HD cases. When low levels of MHc class I expression were found (mainly in EBV- cases), these were not associated with low levels of the transporter protein associated with antigen presentation 1 (TAP-1). The relatively high levels of MHC class I expression in H-RS cells in EBV+ HD cases were accompanied by significantly higher numbers of activated cytotoxic T lymphocytes (CTLs) as shown by the presence of increased numbers of CD8 and granzyme B+ lymphocytes. However, these cells were only sporadically detected in the close vicinity of the H-RS cells. These data suggest that mechanisms other than downregulation of MHC class I or TAP-1 expression on H-RS cells are involved in the failure of the immune system to eradicate EBV harboring H-RS cells. Probably, the function of activated CTLs is locally inhibited by the H-RS cells or by reactive cells in the vicinity of the H-RS cells.

Adolescent↗
PubMed1996

Human papillomavirus--the most significant risk determinant of cervical intraepithelial neoplasia.

Sexual behavior has been consistently identified as a major risk factor for cervical cancer. Population-based studies have demonstrated that risk related to sexual activity is mediated by human papillomavirus (HPV) infection. We conducted a case-control study of 199 cases with low-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions as defined by cytology and 1000 control women selected from an ongoing prospective cohort study in Copenhagen, Denmark. Furthermore, 131 women with equivocal smears (atypical squamous cells of undetermined significance) were examined as a separate borderline case group. At enrollment, all women had a personal interview and a gynecological examination including cervical swabs for HPV testing and a Pap smear. HPV testing was performed using a combination of general primer 5/6-mediated and type-specific polymerase-chain-reaction-based methods. Cervical HPV infection was by far the most significant risk factor for cervical squamous intraepithelial lesions. The relationship with HPV was observed for all grades, while strength of association was greater for more severe lesions. The importance of the previously identified epidemiological risk factors for cervical neoplasia was also demonstrated. However, most of the effect of these factors could be explained by taking HPV infection into account, except for schooling and smoking. Non-use of barrier contraceptives and smoking were the only significant risk factors in HPV-positive women. In HPV-negative women, a residual effect existed for different measures of sexual activity, and use of oral contraceptives and smoking constituted significant risk determinants Overall, 66% of cases could be attributed to HPV; however, if the results were restricted to histologically confirmed high-grade lesions, the proportion of cases that could be attributed to HPV infection increased to 80%.

Adult↗
PubMed1996

Expression of HOXC4, HOXC5, and HOXC6 in human lymphoid cell lines, leukemias, and benign and malignant lymphoid tissue.

Besides their regulatory role in embryogenesis, homeobox (HOX) genes are expressed in a specific manner in hematopoietic cell lineages, implying a role in the molecular regulation of hematopoiesis. Some HOX C cluster genes are found to be expressed in lymphoid cells of mice and humans. Their function and expression in normal hematopoiesis are still largely unknown. We have studied the mRNA expression of HOXC4, HOXC5, and HOXC6 in several stages of lymphocyte maturation by reverse transcriptase-polymerase chain reaction (RT-PCR) and RNA in situ hybridization (RISH). We examined CD34+/CD38low and CD34+/CD38high cells obtained from normal donor bone marrow (BM), a panel of 19 lymphoid cell lines, several types of leukemias and non-Hodgkin's lymphomas (NHL), and lymphocytes isolated from tonsillar tissue and peripheral blood (PB). HOXC4 and HOXC6 were found to be expressed during maturation in B- and T-lymphoid cells. The expression of each gene was found to be initiated at different cell maturation stages. HOXC4 transcripts were present in CD34+/CD38low cells, which are thought to comprise stem cells and noncommitted progenitor cells, and in subsequent stages to terminally maturated lymphoid cells. HOXC6 expression is initiated in equivalents of prothymocyte and pre-pre-B cell stage and remains present in mature cells. However, HOXC5 is only expressed in neoplastic cell lines and in neoplastic cells of NHL, but not in CD34+ BM cells, nor in resting or activated lymphoid cells isolated from tonsil, PB, or in leukemia cells. In cell lines, weak expression of HOXC5 is initiated in equivalents of pre-B cell and common thymocyte stage and is continuously expressed in mature cell lines. Semi-quantitative RT-PCR showed that expression levels of HOXC5 were much lower than those of HOXC4 and HOXC6; furthermore an increase of expression of HOXC4, HOXC5, and HOXC6 during lymphoid cell differentiation was demonstrated. Thus, mainly mature lymphoid cell lines and neoplastic cells of NHL do express HOXC5, in contrast to the lack of expression in normal lymphoid cells and leukemias. These findings suggest involvement of HOXC5 in lymphomagenesis.

Base Sequence↗
PubMed1996

A non-radioactive PCR enzyme-immunoassay enables a rapid identification of HPV 16 and 18 in cervical scrapes after GP5+/6+ PCR.

In previous studies, general primer mediated PCR (GP5+/6+ PCR) was applied successfully to detect a broad spectrum of human papillomaviruses (HPV) in cervical scrapes. In order to facilitate PCR based HPV detection and typing, a colourimetric microtitre plate based hybridisation assay was developed. The method utilised one biotinylated primer (bio-GP6+) in the GP-PCR. Biotinylated PCR products were captured on streptavidin coated microtitre plates, denaturated and hybridised to digoxigenin (DIG) labelled HPV specific internal oligo probes. The DIG labelled hybrids were detected using an enzyme immunoassay (EIA). Since HPV 16 and 18 are the most common HPV types found in cervical carcinomas, this approach was initiated for these two types. Cross-hybridisation reactions were not detected when the specificity of this PCR-EIA for HPV 16 and 18 was tested on a panel of 20 different HPV genotypes. The sensitivity of the assay was found to be between 10 and 100 HPV 16 and 18 viral genomes in a background of 100 ng cellular DNA. This was similar to the detection limit of Southern blot analysis of PCR products with radioactively labelled oligonucleotides. A group of cytomorphologically normal (n = 89) and abnormal (n = 96) cervical scrapes were composed of HPV 16 and HPV 18 positive and HPV negative scrapes. All HPV 16 and 18 positive smears were detected by PCR-EIA. These results indicate that PCR-EIA has the potential for a rapid and sensitive HPV DNA test for day-to-day routine examination of cervical scrapes.

Antibodies, Viral↗
PubMed1996

Extracellular matrix and beta 1 integrin expression in nodal and extranodal T-cell lymphomas.

Since non-Hodgkin's lymphoma (NHL) cells interact with surrounding structures similarly to their normal counterparts, micro-environmental changes and the aberrant expression of adhesion molecules are considered to be of importance in lymphomagenesis. In this immunohistochemical study, the composition of several extracellular matrix (ECM) components and the expression of their beta 1 integrin receptors were examined in nodal and extranodal T-cell NHLs. Except for the T-lymphoblastic NHLs, almost all T-NHLs displayed abundant deposition of matrix and considerable expression of the alpha 4 and beta 1 integrin chains. This is in contrast to B-cell NHLs, which show ECM patterns comparable to those in reactive lymphoid tissue or, in cases of high-grade malignancy, active matrix degradation and very low expression or absence of beta 1 integrins, as previously described. This difference is probably based on distinct cytokine production in B- and T-cell malignancies. As in B-NHL, nodal and extranodal T-NHLs of the same morphological subtype exhibit identical ECM patterns, which suggests that malignant lymphoid cells of both B and T origin create at least part of their own specific micro-environment.

Collagen↗
PubMed1996

Distinctive adhesion pathways are involved in epitheliotropic processes at different sites.

Intraepithelial migration of lymphoid cells (epitheliotropism) is a biological process that can be observed under various physiological and pathological conditions. Recently, epitheliotropism was proposed to be a multi-step process, involving interactions of lymphoid cells with both epithelial basement membrane (EBM) and epithelial cells. In the present study we analysed by immunohistochemistry the adhesion mechanisms that are potentially involved in epitheliotropism of lymphoid cells in various disorders, such as tonsillar hyperplasia, coeliac disease, malignant lymphomas of mucosa-associated lymphoid tissue (MALTomas), and mycosis fungoides (MF). The combinations of adhesion molecules expressed on the participating lymphoid and epithelial cells varied among these disorders. These findings suggest that the adhesion pathways utilized in epitheliotropism may be associated with the nature of the lymphoid cell (reactive or neoplastic/B or T) and/or the site of the epithelium involved. In some cases the specificity of the process was determined by the adhesion mechanism involved in the lymphocyte-EBM interaction, as in the case of alpha 3 beta 1 integrin/laminin-5 in MF, and in others by the adhesion mechanisms involved in the interaction between lymphoid and epithelial cells, such as alpha 4 integrin/VCAM-1 in tonsillar hyperplasia and alpha E beta 7/E-cadherin in coeliac disease.

Celiac Disease↗
PubMed1996

Epstein-Barr virus and human T-cell lymphomas.

Epstein-Barr virus has been classically associated with certain B-lymphocytic benign and malignant proliferations. However, using molecular biological techniques it becomes clear that EBV is also associated with several T-NHL in non-immunocompromised patients. The distribution of EBV-associated T-NHL seems to be site-restricted, i.e. in about 100% of the nasal T-NHL and in 20% of the lung and gastrointestinal lymphomas and rarely in primary cutaneous T-cell lymphomas. Moreover, the expression of the LMP1 protein seems to be associated with a poor prognosis. In this section the role of EBV in the pathogenesis of T-NHL will be discussed.

Gastrointestinal Neoplasms↗
PubMed1996

Age-dependence of human papillomavirus DNA presence in oral squamous cell carcinomas.

The aetiology of oral cancer is thought to be multifactorial. Apart from the two known major risk factors (tobacco and alcohol), a viral aetiology has been proposed, with special reference to human papillomavirus (HPV). 35 cases of oral squamous cell carcinoma (OSCC), seen at the Departments of Oral & Maxillofacial Surgery and Oral Pathology and Otolaryngology of the Free University of Amsterdam, were analysed as well as 12 biopsies of clinically and histologically normal gingival mucosa collected from healthy individuals after tooth extractions, using the polymerase chain reaction (PCR) and two different sets of primers that are able to detect a broad spectrum of HPV types. An overall HPV positivity of 54.3% in OSCC was found, the majority of positive cases (78.9%) harbouring HPV type 16. In contrast, no positivity for HPV was detected in the clinically normal oral mucosal samples analysed. Furthermore, a significant association between HPV presence and age was found: patients older than 60 years showed a lower prevalence of the virus (29.4%) compared with patients below this age (77.8%) (P < 0.05). The results from the present study suggest an association between HPV and OSCC, particularly in patients under the seventh decade.

Adult↗
PubMed1996

Conization for cervical intraepithelial neoplasia is followed by disappearance of human papillomavirus deoxyribonucleic acid and a decline in serum and cervical mucus antibodies against human papillomavirus antigens.

OBJECTIVE: Our purpose was to investigate whether conization for cervical intraepithelial neoplasia eliminates human papillomavirus deoxyribonucleic acid and effects the levels of serum and cervical mucus antibodies against human papillomavirus antigens. STUDY DESIGN: Analysis of paired cervical brush and serum samples taken from 23 women with cervical intraepithelial neoplasia before and 16 to 27 months after conization was performed for presence of human papillomavirus deoxyribonucleic acid by polymerase chain reaction and for human papillomavirus antibodies by enzyme-linked immunosorbent assay. RESULTS: Four women had recurrent cervical intraepithelial neoplasia, whereas 19 women were disease free. Eighteen of 23 women were positive for human papillomavirus deoxyribonucleic acid before treatment. At follow-up only the 4 women with recurrent cervical intraepithelial neoplasia were positive. Serum immunoglobulin G levels and A levels and immunoglobulin A levels in cervical mucus against most of the tested human papillomavirus antigens had declined at follow-up. CONCLUSIONS: Human papillomavirus deoxyribonucleic acid was regularly eliminated and human papillomavirus antibody levels, especially local immunoglobulin A, declined after efficient treatment, suggesting that conization may be effective for treating the underlying human papillomavirus infection.

Adult↗
PubMed1996

Primary signet-ring cell carcinoma of the urinary bladder.

Signet-ring cell carcinoma of the urinary bladder is a rare tumour, accounting for approximately 0.24% of all bladder malignancies. In this study, the clinicopathological findings in 13 cases are described. This malignancy is far more common in men than in women (ratio 11:2). The distribution by age and clinical symptoms can not distinguish it from transitional cell carcinoma. The tumour behaves like other high grade malignancies, presenting frequently at an advanced stage, and having an unfavourable clinical outcome. No special therapy seems superior to another.

Adult↗
PubMed1996

The incidence of micrometastases in neck dissection specimens obtained from elective neck dissections.

Although modern imaging techniques become more accurate for the assessment of lymph node metastases in the neck as criteria and technology evolve, micrometastases remain occult with any technique. Even the routine histopathological examination of neck dissection specimens is unable to detect all micrometastases. Because knowledge on the incidence of micrometastases in the clinically NO neck might be of importance for decision making regarding elective treatment, a retrospective study on 96 elective neck dissections was conducted. Meticulous histopathological examination of the neck dissection specimens yielded 3092 lymph nodes of which 67 (2.2%) were tumor-positive. Twenty-six of these 67 lymph node metastases were micrometastases. Of the 36 tumor-positive neck dissection specimens, 21 contained micrometastases. In 9 tumor-positive specimens only micrometastases were found. This high incidence of micrometastases has important implications for the diagnostic work-up, the treatment, and histopathological examination of the NO neck.

Carcinoma, Squamous Cell↗
PubMed1996

T cell proliferative responses against human papillomavirus type 16 E7 oncoprotein are most prominent in cervical intraepithelial neoplasia patients with a persistent viral infection.

T cell proliferative responses against human papillomavirus type 16 (HPV-16) E7 protein were studied in relation to HPV status over time in 51 women originally diagnosed with abnormal cervical cytology and participating in a follow-up study. HPV-16-positive patients were grouped as having either a persistent, a cleared or a fluctuating HPV-16 infection as determined by PCR in consecutive cervical smears up until the moment of testing. Positive proliferative responses against HPV-16 E7 were found in 15/26 patients with a persistent, cleared or fluctuating HPV-16 infection (57.7%). In contrast, 0/15 patients who had been typed HPV-negative during follow-up showed positive responses (P = 0.0005). Further analysis showed positive responses to be more frequent in patients with persistent HPV-16 infections and stable or progressing cervical lesions (8/9 patients reactive, 88.9%) as compared to patients with cleared or fluctuating HPV-16 infections and stable or regressing cervical lesions (7/17, 41.1%, P = 0.04). The relatively strong T cell proliferative responses against HPV-16 E7 observed in patients with a persistent HPV-16 infection and progressive cervical lesions indicate that the effectivity of such responses cannot be predicted and apparently depends on additional factors.

Adult↗
PubMed1996

RNA amplification by nucleic acid sequence-based amplification with an internal standard enables reliable detection of Chlamydia trachomatis in cervical scrapings and urine samples.

In the present study, the suitability of RNA amplification by nucleic acid sequence-based amplification (NASBA) for the detection of Chlamydia trachomatis infection was investigated. When comparing different primer sets for their sensitivities in NASBA, use of both the plasmid and omp1 targets resulted in a detection limit of 1 inclusion-forming unit (IFU), while the 16S rRNA appeared to be the most sensitive RNA target for amplification (10(-3) IFU). In contrast, for DNA amplification by PCR, the plasmid target was optimal (10(-2) IFU), which is 10 times less sensitive than rRNA NASBA. To exclude false negativity in NASBA detection because of inhibition of amplification and/or inefficient sample preparation, an internal standard was developed. The internal control was added prior to sample preparation. This 16S rRNA NASBA with an internal control was compared with a plasmid DNA PCR by using a group of C. trachomatis-negative (n = 41) and -positive (n = 37) cervical scrapings, as determined by enzyme immunoassay (EIA). In addition, urine samples from the EIA-positive women were tested (n = 17). Both NASBA and PCR assays were able to detect C. trachomatis in all EIA-positive cervical scrapings, the corresponding urine samples, and two samples from the EIA-negative group. The internal NASBA standard was found clearly in all EIA-negative samples. In conclusion, these results indicate that detection of C. trachomatis by RNA amplification by NASBA with an internal standard is a suitable and highly sensitive detection method, with potential use in the diagnosis of urogenital C. trachomatis infections with cervical scrapings as well as urine specimens.

Bacterial Outer Membrane Proteins↗
PubMed1996

Expression of Epstein-Barr virus encoded latent genes in nasal T cell lymphomas.

AIMS: To determine the expression of Epstein-Barr (EB) virus encoded latent genes in nasal T-cell lymphomas in The Netherlands. METHODS: Seven europid (Dutch) cases of nasal T cell lymphoma were investigated for the presence of EB virus by RNA in situ hybridisation (EBER). The expression of the EB virus encoded genes BARF0, EBNA1, EBNA2, LMP1, LMP2A, LMP2B, and ZEBRA was studied at the mRNA level using reverse transcriptase polymerase chain reaction. At the protein level the expression was investigated of EBNA2 and LMP1 by immunohistochemistry. RESULTS: In all seven nasal T cell lymphomas EBER was detected in the nuclei of virtually all tumour cells. BARF0 mRNA was detected in all samples. EBNA1 mRNA was found in six cases, LMP1 mRNA in five, LMP2A mRNA in three, LMP2B mRNA in one, and ZEBRA mRNA in one. EBNA2 mRNA was not found in any case. At the protein level occasional LMP1 positive tumour cells were seen in only one case. The EBNA2 protein was not detected. CONCLUSIONS: Nasal T cell lymphomas in The Netherlands are strongly associated with EB virus. The virus shows a type II latency pattern (EBNA1+, LMP1+, EBNA2-) that seems to be similar to the EB virus associated nasal T cell lymphomas in oriental countries.

Base Sequence↗
PubMed1996

Expression of epstein-barr virus encoded nuclear antigen 1 in benign and malignant tissues harbouring EBV.

AIMS: To determine levels of expression of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) in benign and malignant tissues harbouring EBV in relation to EBNA1 promoter usage. METHODS: Expression of EBNA1 was investigated by means of immunohistochemistry using a mixture of two EBNA1 specific monoclonal antibodies, 1H4-1 and 2B4-1. The presence of EBV was detected by EBER1/2 RNA in situ hybridisation. Detection of promoter specific EBNA1 transcripts was by RT-PCR analysis. RESULTS: EBNA1 positive cells were detected in all 20 EBV associated B cell lymphomas, 18 of which had arisen in immunocompromised patients; in eight of nine EBV associated T cell lymphomas; in 11 of 27 EBV positive cases of Hodgkin's disease; and in reactive lymphoid tissue harbouring EBV, including four cases of infectious mononucleosis. A diffuse EBNA1 staining pattern was observed in most of the EBV associated B cell lymphomas and was comparable with the EBER1/2 staining pattern. In the T cell lymphomas the number of EBNA1 positive cells was usually considerably less than the number of EBER1/2 positive ones. RT-PCR analysis revealed that in tumours with restricted EBNA1 expression-that is, T cell lymphomas and Hodgkin's disease lesions, EBNA1 transcripts were usually generated only by the F/Q promoter, whereas in B cell lymphomas EBNA1 transcripts were usually generated by both the C/W and F/Q promoters. CONCLUSIONS: EBNA1 is expressed in all types of tissue harbouring EBV, but the level of expression varies greatly. This may be the result of differential promoter usage.

Antigens, Viral↗