PubMed Health⌕ Search

Biomedical subjects

C J Meijer

Publications and source records attributed to C J Meijer.

At least 19 recordsLinked to original sources
PubMed1995

Integrated human papillomavirus type 16 and loss of heterozygosity at 11q22 and 18q21 in an oral carcinoma and its derivative cell line.

A human papillomavirus (HPV) type 16 containing oral squamous cell carcinoma cell line 93VU147T at early passage was demonstrated to match its primary tumor with regard to HPV status and loss of heterozygosity at loci potentially involved in HPV-mediated carcinogenesis. DNA in situ hybridization of the cell line and the primary tumor revealed the presence of HPV 16 DNA clonally associated with the neoplastic cells. One- and two-dimensional Southern blot hybridization suggested HPV 16 to be integrated in the host genome at over hundred copies/cell. An identical restriction enzyme profile was observed for the tumor and the cell line. Viral DNA integration was confirmed by fluorescence in situ hybridization on metaphase spreads of the cell line, which revealed six stained loci comprising one at 15q14-15 and five at cytogenetically unidentifiable chromosomes. In addition, the tumor and the cell line displayed mRNA expression of the E6/E7 region encoding the viral oncoproteins, as determined by reverse transcription-PCR. Northern blot analysis of the cell line revealed three major and three minor transcripts harboring E6/E7 sequences. Both the primary tumor and cell line showed loss of heterozygosity at the 11q22 (D11S35) and 18q21 (DCC) loci. These data support a role for HPV 16 in the development of a subset of oral cancers, presumably in concert with loss of function of tumor suppressor genes at 11q and 18q.

Carcinoma, Squamous Cell↗
PubMed1995

BHRF1, the Epstein-Barr virus (EBV) homologue of the BCL-2 protooncogene, is transcribed in EBV-associated B-cell lymphomas and in reactive lymphocytes.

BHRF1, one of many Epstein-Barr virus (EBV)-encoded proteins, shows strong functional homology to the human bcl-2 proto-oncogene product, a protein involved in the pathogenesis of a subset of B-cell lymphomas, ie, follicle center cell lymphomas (FCCL). We have investigated the presence of possible latent and lytic transcripts of BHRF1 using a reverse transcriptase-polymerase chain reaction (RT-PCR)-based assay in a group of EBV-associated B-cell lymphomas in patients with (N = 5) or without overt immunodeficiency (N = 4), in T-cell lymphomas (N = 9), and in cases of Hodgkin's disease (N = 6). BHRF1 transcription was found consistently in EBV-associated (ie, diffuse EBER 1/2-positive) B-cell lymphomas in patients with or without immune deficiency, whereas in EBV-associated T-cell lymphomas or in EBV-associated Hodgkin's disease, BHRF1 transcription was only detected in two T-cell lymphomas and one case of Hodgkin's disease, which also harbored EBER 1/2-positive reactive cells. Moreover, weak BHRF1 signals were found in two T-cell lymphomas where EBER 1/2 expression was detected mainly in sporadic reactive lymphocytes and in one reactive tonsil with sporadic EBER 1/2-positive lymphocytes. BHRF1 transcripts were found to be generated by the C or W promoter (associated with viral latency) and/or by the H promoter (associated with the virus lytic cycle). In all cases with H promoter-derived BHRF1 transcripts, transcripts encoding ZEBRA were also detected, suggesting a reactivation of the virus lytic cycle. Analysis of other EBV genes revealed transcription of BARFO in all tested EBV-harboring tissues. Transcription of EBNA1 and LMP1 was usually detected, whereas EBNA2 transcription was found exclusively in B-cell lymphomas in immunocompromised patients. These data demonstrate that BHRF1 transcripts are exclusively found in EBV-associated B-cell lymphomas. When BHRF1 transcripts are detected in T-cell lymphomas or in Hodgkin's disease, it is probably due to the presence of reactive EBER 1/2-positive lymphocytes. The consistent transcription of BHRF1 in EBV-associated B-cell lymphomas suggests a possible pathogenic role for this gene product in EBV-positive B-cell lymphomas analogous to bcl-2.

Base Sequence↗
PubMed1995

The presence of persistent high-risk HPV genotypes in dysplastic cervical lesions is associated with progressive disease: natural history up to 36 months.

To evaluate the clinical significance of HPV genotyping for the prediction of progressive cervical intraepithelial neoplasia (CIN) in women with cytomorphologically abnormal smears, a prospective, blind, non-intervention study was performed. A total of 342 patients screened with cytomorphologically abnormal cervical smears were monitored every 3-4 months by cervical cytology, colposcopy and HPV testing using PCR. Women with progressive CIN disease were defined as patients developing lesions with a colposcopic impression of CIN III over more than 2 quadrants or resulting in a cytological smear equivalent to Pap 5. These patients were subsequently treated according to standard procedures. If any doubt arose about the true status of the patients (n = 75) these patients were censored and biopsied. The mean follow-up time was 16.5 months (range 3-36 months). Nineteen women showed progressive CIN disease and all appeared to be continuously HPV-positive from the start of the study. At biopsy, all these patients were histologically classified as CIN III. Seventeen of these women were positive for high-risk HPV types. Two cases were classified as still unidentified HPV. No progression was seen in the absence of HPV DNA or in the presence of low-risk HPV types. In life-table analysis the cumulative rate of progressive, histologically verified CIN disease was 17% after 36 months. Further analyses showed that other risk factors such as age, sexarche, number of sexual partners or smoking hardly influenced the effect of HPV on progression. The results show that the continuous presence of high-risk HPV types in women with cytomorphologically abnormal smears is a strong marker for progressive CIN disease.

Adolescent↗
PubMed1995

HPV prevalence in cytomorphologically normal cervical scrapes of pregnant women as determined by PCR: the age-related pattern.

Diverging data exist on human papillomavirus (HPV) prevalence in cytomorphologically normal scrapes during pregnancy. The prevalence of HPV was therefore investigated by polymerase chain reaction method (PCR) in cytomorphologically normal scrapes of 709 pregnant women and 3,948 non-pregnant women visiting the same hospital during the same time period. The prevalence of all types of HPV among pregnant women was 9.6% (68/709) and the high risk HPV types of 16 and 18 were found in 3.1% (22/709). In the non-pregnant women the prevalence of all types of HPV was 10.9% (432/3,948) with 2.9% (116/3,948) HPV types 16 and 18. The highest prevalence of HPV was present in women at younger ages in both groups. With increasing age the prevalence declines from about 19% (15-25 yrs) to 5% (40-49 yrs). The age-adjusted odds ratio of prevalence of all types of HPV in pregnant versus non-pregnant women was 0.73 (95% CI 0.56-0.96, P = 0.025) and statistically significant. When HPV types 16 and 18 were considered, significant differences were not found. HPV of all types and types 16/18 prevalence was higher in the second half of pregnancy than in the first part but did not reach statistical significance. High HPV copy numbers in the scrapes were found during the first half of the pregnancy and not during the second half using a semi-quantitative HPV 16/18 PCR detection method. Since the difference in HPV prevalence between non-pregnant and pregnant women is very small, it is concluded that HPV prevalence in cytomorphologically normal smears is hardly influenced by pregnancy.

Adolescent↗
PubMed1995

Neuroendocrine neoplasms of the larynx. Importance of the correct diagnosis and differences between atypical carcinoid tumors and small-cell neuroendocrine carcinoma.

Findings in the present study have confirmed that the diagnosis of neuroendocrine tumors of the larynx (NETL) requires that a panel of neuroendocrine markers and electron microscopy be performed. This means that the clinician must be aware of the clinical presentations of such patients and should send fresh biopsy specimens to the clinical laboratory for optimal tissue studies. As shown in this study, the possibility of misdiagnosis of an atypical carcinoid tumor (ACT) is rather high. In establishing a diagnosis, a part of the material should be fixed for conventional histology, a part for immunohistochemistry and a part for electron microscopy. The correct diagnosis of NETL is obviously of great importance for subsequent treatment and prognosis. Patients with the diagnosis of ACT of the larynx require surgical treatment. Our findings also show that small-cell neuroendocrine carcinomas of the larynx should be considered to be a disseminated disease at initial presentation. A metastatic workup is necessary, but radical surgical procedures should be avoided. The combination of radiotherapy and chemotherapy is always indicated.

Aged↗
PubMed1995

Peripheral primitive neuroectodermal tumour and extra-osseous Ewing's sarcoma; a histological, immunohistochemical and DNA flow cytometric study.

Although peripheral primitive neuroectodermal tumour (pPNET) and extra-osseous Ewing's sarcoma (EES) are thought to be closely related neoplasms, their clinical behaviour differs considerably. To determine the clinical relevance of the Schmidt classification scheme for differentiating pPNET and EES, 20 tumour specimens of poorly differentiated round cell tumours were evaluated. In addition, the diagnostic value of several neural markers and the prognostic value of quantitative morphological variables (DNA ploidy, S-phase fraction, and the mitotic activity) were assessed. Homer-Wright rosettes were present in 9 tumours. Neuron specific enolase (NSE) was expressed in 11 tumours, 8 of which expressed a second neural marker (CD57, S100, or neurofilament). According to the Schmidt classification, 11 pPNET and 5 EES were distinguished. HBA-71 was exclusively expressed in pPNET and EES. The remaining tumours were classified as sarcoma not otherwise specified (n = 2), rhabdomyosarcoma (n = 1), and desmoplastic tumour with divergent differentiation (n = 1). EES611 patients fared significantly better than the pPNET patients (100% versus 42% 5-year survival). Neither DNA ploidy nor S-phase fraction assessed in 12 evaluative histograms (9 pPNET and 3 EES), nor mitotic activity yielded information of additional prognostic value. On the basis of this study and the Schmidt classification scheme, it can be concluded that if the diagnosis of EES and pPNET is based on light microscopy (Homer-Wright rosettes) and/or immunohistochemistry (at least two neural markers, i.e. NSE, S-100, CD57, and neurofilament), the classification provides important clinical information. Furthermore, positivity for HBA-71 is helpful in differentiating pPNET and EES from all other small round cell tumours.

Adolescent↗
PubMed1995

Processing of long-stored archival cervical smears for human papillomavirus detection by the polymerase chain reaction.

The efficiency of a freeze-thaw method, a proteinase K/Tween 20 lysis method and a guanidinium isothiocyanate/silica beads method for DNA extraction from fixed and Papanicolaou-stained cells from the cervical cancer cell line Siha was measured by beta-globin polymerase chain reaction (PCR). The GTC/silica beads method, which appeared superior, revealed a human papillomavirus (HPV) general primer-mediated PCR sensitivity of 50-500 copies of HPV 16 per sample using dilutions of fixed and stained Siha cells. Application to archival cervical smears (n = 116) revealed that the yield and size of amplifiable DNA decreases with storage time. The longer the storage time, the more repetitions of the whole procedure, including the lysis step, were required to extract sufficient amplifiable DNA. In this way, an overall beta-globin PCR positivity for 98% of the smears was reached. Further analysis revealed that a maximum size of 200 bp could be amplified from smears stored for up to 9 years. The method was validated by demonstrating by PCR the same HPV types in archival smears and corresponding cervical biopsies of cervical cancer patients. In conclusion, the GTC/silica beads method appears suitable to process archival cervical smears for HPV detection by PCR. provided that stepwise adjustments are made until beta-globin PCR positivity is obtained and primers are chosen which amplify a maximum of about 200 bp.

Base Sequence↗
PubMed1995

The drug resistance-related protein LRP is the human major vault protein.

Multidrug-resistant cancer cells frequently overexpress the 110-kD LRP protein (originally named Lung Resistance-related Protein). LRP overexpression has been found to predict a poor response to chemotherapy in acute myeloid leukaemia and ovarian carcinoma. We describe the cloning and chromosome localization of the gene coding for this novel protein. The deduced LRP amino acid sequence shows 87.7% identity with the 104-kD rat major vault protein. Vaults are multi-subunit structures that may be involved in nucleo-cytoplasmic transport. The LRP gene is located on chromosome 16, close to the genes coding for multidrug resistance-associated protein and protein kinase C-beta, and may mediate drug resistance, perhaps via a transport process.

Amino Acid Sequence↗
PubMed1995

Localization and identification of granzymes A and B-expressing cells in normal human lymphoid tissue and peripheral blood.

Cytoplasmic granules from activated natural killer (NK) and cytotoxic T lymphocytes (CTL) contain a pore-forming protein, perforin, and several homologous serine proteinases called granzymes. Expression of these proteins correlates with the cytolytic potential of cytotoxic lymphocytes. Using a panel of MoAbs specific for human granzyme A and B, respectively, expression of these proteinases in non-pathological lymphoid tissue and peripheral blood lymphocyte (PBL) subpopulations was investigated. Using immunohistochemistry and double stainings, the phenotype of granzyme-expressing cells in lymphoid tissue was investigated. Granzyme-positive cells were detected in all lymphoid tissues tested. No large differences in the number and distribution between granzyme A- and granzyme B-positive cells were observed. The highest number of positive cells was located in the red pulp of the spleen. Significant numbers were detected in tonsil, lymph nodes, liver and thymus. Low numbers were present in the lamina propria of non-inflamed stomach, small intestine and colon. Phenotypic analysis and cell sorting showed that most of the granzyme-positive cells in lymphoid tissue and PBL consisted of CD3-CD16+CD56+ lymphocytes. Hardly any granzyme-positive CD3+CD8+ CTL were present in peripheral blood. The synthesis of granzyme A as well as B by both CD3+CD16+CD56+ and CD3+CD8+ cells in peripheral blood was increased upon IL-2 stimulation. These results indicate that in normal lymphoid tissue the predominant cytolytic cell population is formed by the NK cells, and activated CTL are rare.

Antibodies, Monoclonal↗
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↗
PubMed1995

Group-specific differentiation between high- and low-risk human papillomavirus genotypes by general primer-mediated PCR and two cocktails of oligonucleotide probes.

In recent years, general primer-mediated PCR assays have been developed to detect a broad spectrum of human papillomavirus (HPV) genotypes. In this study, a procedure enabling a simple group-specific differentiation of high-risk (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -54, -56, and -58) and low risk (HPV-6, -11, -34, -40, -42, -43, and 44) HPVs following an HPV general primer-mediated (GP5+/GP6+) PCR is presented. By computer-assisted sequence analysis, oligonucleotides (30-mers) specific for 19 different HPV genotypes were selected from the internal part of the 150-bp GP5+/GP6(+)-amplified region. These oligo probes were tested for specificity in a Southern blot analysis of PCR products derived from the same panel of HPV types. No cross-hybridizations were found. The sensitivities of the oligo probes varied from the femtogram level for the well-amplified HPV types like HPV-16 and -18 to the picogram level for the less-well amplified HPV types like HPV-39 and -51. These sensitivities were reached when the oligo probes were applied both individually and in a cocktail. On the basis of these results, two cocktail oligo probes that enabled a specific and sensitive differentiation between low- and high-risk HPV types were composed.

Base Sequence↗
PubMed1995

Immunohistochemical demonstration of different latent membrane protein-1 epitopes of Epstein-Barr virus in lymphoproliferative diseases.

AIM: To compare the immunoreactivity of monoclonal antibodies S12 and CS1-4, which recognise different epitopes of the Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1), in EBV associated benign and malignant lymphoproliferative disorders and control tissues processed using different methods. RESULTS: Both monoclonal antibodies gave comparable results on frozen tissue sections and formalin fixed, paraffin wax embedded samples from cases with Hodgkin's disease and infectious mononucleosis. In all cases S12 stained more cells than CS1-4. For EBV associated B and T non-Hodgkin's lymphomas, frozen tissue sections yielded better LMP-1 staining results than formalin fixed material. Again, in all these cases S12 stained more cells and gave stronger results than CS1-4. For EBV negative tissues, both monoclonal antibodies showed cross-reactivity with melanocytic-like cells in the basal cell layer of the skin, synaptophysin-like staining in layers three and four of the cortex of the brain, and myelin-like staining in peripheral nerves and peripheral ganglion cells. Staining with S12 was always much stronger. Moreover, in contrast to CS1-4, S12 stained pancreatic islands in formalin fixed material but not in frozen tissue sections and sporadically stained solitary epithelial cells in the large bowel especially in formalin fixed tissue sections. CS1-4 also cross-reacted with myoepithelial cells around hair follicles and other adnexa of the skin. CONCLUSION: The results indicate that for optimal detection of LMP-1, S12 yields better results than CS1-4 and that tissue processing is very important especially when B and T non-Hodgkin's lymphomas are examined.

Antibodies, Monoclonal↗
PubMed1995

Distribution of OV-TL 3 and MOv18 in normal and malignant ovarian tissue.

AIMS: To analyse the distribution of OV-TL 3 and MOv18 in normal ovarian tissue to determine which antibody is most suitable for (radio)immunotherapy of ovarian carcinoma. METHODS: The distribution of OV-TL 3 and MOv18 was determined using immunohistochemistry and flow cytometry. RESULTS: Epithelial and other cells in many tissues, and leucocytes in peripheral blood, bone marrow and spleen stained positively with OV-TL 3. The staining pattern of MOv18 in normal tissues was more restricted and was confined to epithelial cells in the lung, kidney, pancreas, salivary gland, ovary, Fallopian tubes, and cervix. Reactivity was also observed with pneumocytes in the lung, tubuli in the kidney, acinar cells in the salivary gland and pancreas, in the placenta, and with Kupffer cells in the liver. The staining pattern of chimeric MOv18 was identical with the murine form. OV-TL 3 and MOv18 reacted with 100% and 98% (45/46) of the 46 tested epithelial ovarian cancers, respectively. In ovarian carcinoma tissue homogeneous staining of epithelial cells was observed with OV-TL 3 and more heterogeneous staining with MOv18. In 12 and nine patients, respectively, a difference in staining intensity for OV-TL 3 and MOv18 was observed between various tumour samples from the same patient. CONCLUSION: MOv18 has greater therapeutic potential because of its restricted reactivity with normal tissues and especially, in contrast to OV-TL 3, its lack of reactivity with haematopoietic cells.

Antibodies, Monoclonal↗
PubMed1995

Human papillomavirus in false negative archival cervical smears: implications for screening for cervical cancer.

AIM: To assess the value of detecting human papillomavirus (HPV) DNA in false negative archival cervical smears in population based screening programmes for cervical cancer. METHODS: Cytomorphologically classified false negative archival Pap smears (n = 27) taken from 18 women up to six years before cervical cancer was diagnosed were blindly mixed with 89 smears from hospital patients with a variety of gynaecological complaints and tested for HPV by the polymerase chain reaction (PCR). Corresponding cervical cancer biopsy specimens were also available for HPV analysis. Neither the examining cytopathologist nor the molecular biologist was aware of the study design. RESULTS: HPV DNA was detected in the smears of 16 patients with cervical cancer missed previously by cytology. HPV 16 and 18 were found predominantly in those smears taken up to six years before the diagnosis of cervical cancer. The smears of the two remaining patients were reclassified as inadequate for cytology or contained no suitable DNA for PCR. In 15 patients the same HPV type could be found in the smears and the cervical cancer biopsy specimens. CONCLUSIONS: The results indicate that high risk HPV types can be detected in archival smears classified as false negative on cytology and that cytological screening errors may be reduced if combined with PCR testing for HPV.

DNA, Viral↗
PubMed1995

Chlamydia trachomatis and ectopic pregnancy: retrospective analysis of salpingectomy specimens, endometrial biopsies, and cervical smears.

AIMS: To examine the role of Chlamydia trachomatis in ectopic pregnancy by detection of DNA in archival salpingectomy specimens, and in their preceding cervical specimens and endometrial biopsies, by using the polymerase chain reaction (PCR). METHODS: Archival paraffin embedded salpingectomy tissues (n = 48) from 37 women with ectopic pregnancy were examined for the presence of C trachomatis plasmid and omp1 DNA by PCR. In addition, preceding cervical specimens (n = 58) stored either as cervical cell suspensions or as archival cervical smears, and preceding endometrial biopsies (n = 18), taken 0-5.8 years before the ectopic pregnancy, were examined by PCR for the presence of C trachomatis. RESULTS: C trachomatis DNA was detected in only one of the 48 salpingectomy specimens from 37 women. However, in six of the 37 women, C trachomatis DNA was detected in the genital specimens (cervix and/or endometrial) taken before salpingectomy. C trachomatis infections were mostly found in endometrial or cervical specimens taken more than three years before ectopic pregnancy. No chlamydial DNA was found in endometrial or cervical specimens taken at the same time of the ectopic pregnancy. CONCLUSIONS: Although no C trachomatis DNA was found in salpingectomy specimens, several women with ectopic pregnancy had C trachomatis infections in endometrial and cervical specimens in the past. This suggests that at least in these cases the ectopic pregnancy is a late post-inflammatory complication of an ascending C trachomatis infection resulting in a scarred fallopian tube.

Adult↗