Biomedical subjects

M A Versnel

Publications and source records attributed to M A Versnel.

At least 37 records · Page 2Linked to original sources

PubMed1996

Regulation of differential expression of platelet-derived growth factor alpha- and beta-receptor mRNA in normal and malignant human mesothelial cell lines.

In earlier studies we showed that the expression of patterns of platelet-derived growth factor (PDGF) alpha- and beta-receptors differ between normal and malignant mesothelial cell lines. Normal mesothelial cells predominantly express PDGF alpha-receptor mRNA and protein, whereas most malignant mesothelioma cell lines produce PDGF beta-receptor mRNA and protein. In this paper we studied regulation of this differential PDGF receptor mRNA expression. Such an analysis is of importance in view of the suggested PDGF autocrine activity involving the PDGF beta-receptor mesothelioma cells. The results obtained in this study demonstrate that malignant mesothelioma cell lines are not only capable of PDGF beta-receptor transcription but of alpha-receptor transcription as well, as evidenced from run off analysis and RT-PCR using alpha-receptor specific primers. However, the fact that PDGF alpha-receptor mRNA could not be detected by Northern blot analysis, even after cycloheximide treatment, suggests a difference in steady-state PDGF alpha-receptor mRNA expression levels between normal and malignant mesothelial cell lines, which is likely to be caused by a post-transcriptional mechanism. In normal mesothelial cells a half-life of more than 6 h was observed for PDGF alpha-receptor mRNA. In the majority of malignant mesothelioma cell lines clear PDGF beta-receptor mRNA expression was seen. The half-life of the PDGF beta-receptor transcript was at least 6 h in these cells. In contrast, hardly any PDGF beta-receptor transcription was observed in run off assays in normal mesothelial cells, suggesting that differences in beta-receptor transcriptional initiation most probably account for the inability to clearly detect PDGF beta-receptor transcripts in these cells. Transforming growth factor beta-1 (TGF-beta 1), which is being produced in active form by mesothelial cells was evaluated for its potential role in regulation of the differential PDGF receptor expression in these cells. Stimulation with TGF-beta 1 revealed decreased PDGF alpha-receptor mRNA expression in normal mesothelial cells. The effect on PDGF beta-receptor mRNA in the malignant mesothelioma cell lines was variable. Although the TGF-beta 1 effect cannot entirely explain the differential PDGF receptor expression pattern, TGF-beta 1 may nevertheless play a role in downregulation of an (already) low PDGF alpha-receptor mRNA level in malignant mesothelioma cell lines.

Base Sequence↗

PubMed1996

Expression of platelet-derived growth factor (PDGF) and PDGF receptors in human malignant mesothelioma in vitro and in vivo.

The expression of platelet-derived growth factor (PDGF) and PDGF receptors was studied in human normal and malignant mesothelial cells in vitro and in vivo. Staining with anti-cytokeratin and ME1 antibodies and ultrastructural analysis confirmed the mesothelial nature of the cell lines used to study PDGF and PDGF receptor expression in vitro. Using antibodies, mesothelioma cell lines were found to express PDGF and both the PDGF alpha- and the PDGF beta-receptor, whereas cultured normal mesothelial cells expressed PDGF and PDGF alpha-receptor. This PDGF and PDGF receptor staining pattern largely reflects the earlier described mRNA expression in these cell lines. The only exception was the immunocytochemical detection of PDGF alpha-receptors in the mesothelioma cell lines, which is different from the inability to detect alpha-receptor transcripts on Northern blots. Expression was also investigated in mesothelial cells in vivo. Expression of PDGF was observed in malignant mesothelioma cells on frozen tissue sections. In pleural effusions, a double immunofluorescence staining procedure for PDGF and epithelial membrane antigen (EMA) revealed PDGF expression by EMA-positive malignant mesothelioma cells. PDGF beta-receptors and occasionally PDGF alpha-receptors were detected in frozen tissue sections of malignant mesotheliomas, whereas mesothelioma cells in effusions showed faint expression of only the PDGF beta-receptor. In contrast, in effusions containing non-malignant mesothelial cells, only a very low level of PDGF alpha-receptor could be detected. Taken together, these results indicate that the pattern of PDGF and PDGF receptor expression in mesothelial cells in vivo largely corresponds to expression of PDGF and its receptors in vitro. Malignant mesothelioma cell lines thus constitute a good model system for studies on the role of PDGF in this malignancy. Furthermore, the data reported in this paper are consistent with the idea that an autocrine growth stimulatory effect of PDGF via PDGF receptors may play a role in the pathogenesis of malignant mesothelioma.

Cryopreservation↗

PubMed1996

Expression of ICAM-1 and VCAM-1 in human malignant mesothelioma.

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are cytokine-inducible adhesion molecules which recognize ligands that are highly expressed on leukocytes. Expression of ICAM-1 and VCAM-1 was investigated in tissue sections of 16 cases of malignant mesothelioma (seven epithelial, eight biphasic, and one sarcomatoid) using immunohistochemistry. Neoplastic cells were diffusely and intensely stained for ICAM-1 in all cases. VCAM-1 was detected in 14 of 16 cases. The percentage of VCAM-1-positive tumour cells was more than 50 per cent in eight cases and the staining was observed mainly in epithelial-like cells. VCAM-1 was rarely expressed in other malignant tumours of epithelial origin, being present in only 1 of 58 cases of carcinoma originating from different anatomical sites. At the cellular level, ICAM-1 and VCAM-1 appeared co-distributed, the staining for both being cytoplasmic with a membrane reinforcement. The regulation of VCAM-1 expression by neoplastic mesothelial cells was investigated in vitro using 14 mesothelioma cell lines. ICAM-1 was expressed by cultured cells of all mesothelioma cell lines, even in the absence of cytokines. VCAM-1 was detected in 10-50 per cent of the cells in three non-stimulated mesothelioma cell lines (mero-95, mero-96, and mero-134), and was absent or poorly expressed in the remaining 11. Exposure of a negative cell line (mero-48a) to an optimal concentration of tumour necrosis factor alpha (TNF alpha) or interleukin-13 (IL-13) for 6-18 h resulted in the induction of VCAM-1 mRNA synthesis and in VCAM-1 expression at the membrane level in 60-70 per cent of the cells. These findings are consistent with the possibility that TNF alpha, IL-13, or other activating signals are released in the tumour micro-environment and regulate the expression of VCAM-1 in malignant mesothelioma cells.

Blotting, Northern↗

PubMed1996

Modulation of glucocorticoid receptor expression in human bronchial epithelial cell lines by IL-1 beta, TNF-alpha and LPS.

Bronchial epithelium plays a major role in the regulation of inflammatory reactions in the airways. It is thought to be a possible target for glucocorticoid therapy. Glucocorticoid responsiveness requires the presence of specific glucocorticoid receptors (GR). Until now, little was known about the presence of such receptors in the human bronchial epithelium. In this study we demonstrated the expression of GR messenger ribonucleic acid (mRNA) in two simian virus (SV)-40/adenovirus-transformed human bronchial epithelial cell lines, BEAS S6 and BEAS 2B. In a whole cell dexamethasone binding assay, BEAS S6 and BEAS 2B cells were found to possess (mean +/- SEM) 28.9 +/- 4.4 x 10(3) and 32.1 +/- 5.7 x 10(3) binding sites per cell, respectively, with dissociation constant (Kd) values of 8.2 +/- 1.5 and 8.6 +/- 2.4 nM, respectively. Using electrophoretic mobility shift assays we demonstrated the binding of nuclear translocated GR to specific sites on deoxyribonucleic acid (DNA), named glucocorticoid responsive elements (GRE). Lipopolysaccharide (LPS) and interleukin-1 beta (IL-1 beta) significantly increased the number of GR per cell (median = 312% and 171% of control, respectively; p < 0.05), but significantly reduced the ligand affinity of these receptors, i.e. increased the Kd (median = 410% and 145% of control, respectively; p < 0.05) in BEAS 2B cells. These results indicate that the bronchial epithelium may be an actual target for glucocorticoid therapy. Inflammatory mediators, such as IL-1 beta and LPS, modulate the number and ligand affinity of these GR. Therefore, the response of bronchial epithelium to glucocorticoid therapy may be modulated by airway diseases associated with inflammation.

Adenoviridae↗

PubMed1995

Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression.

Mutations in the WT1 tumor suppressor gene are known to contribute to the development of Wilms' tumor (WT) and associated gonadal abnormalities. WT1 is expressed principally in the fetal kidney, developing gonads, and spleen and also in the mesothelium, which lines the coelomic cavities. These tissues develop from mesenchymal components that have subsequently become epithelialized, and it has therefore been proposed that WT1 may play a role in this transition of cell types. To test the possible involvement of this gene in malignant mesothelioma, we have first studied its expression in a panel of human normal and malignant mesothelial cell lines. WT1 mRNA expression levels varied greatly between the cell lines and no specific chromosomal aberration on 11p, which could be related to the variation in WT1 expression in these cell lines, was observed. Furthermore, no gross deletions rearrangements, or functionally inactivating point mutations in the WT1 coding region were identified. All four WT1 splice variants were observed at similar levels in these cell lines. The WT1 gene encodes a zinc-finger transcription factor and the four protein isoforms are each believed to act as transcriptional repressors of certain growth factor genes. Lack of WTI expression in thus predicted to result in growth stimulation of tumor cells. Binding of one particular WT1 isoform construct to the insulin-like growth factor 2 (IGF2) and platelet-derived growth factor A (PDGFA) gene promoters has been demonstrated to result in repression of these genes in transient transfection studies. Analysis of IGF2 and PDGFA mRNA expression levels compared with WTI mRNA expression levels failed to demonstrate an inverse correlation in the mesothelial cell lines, which endogenously express these genes. Finally, the putative role of WT1 in the transition of cell types was investigated. No obvious correlation between WT1 expression levels and cell morphology of the malignant mesothelial cell lines was evident from this study. Moreover, no change in WT1 expression was observed in normal mesothelial cells which were, by alteration of culture conditions, manipulated to switch from the mesenchymal to epithelial morphology.

Base Sequence↗

PubMed1994

Human ovarian tumors of epithelial origin express PDGF in vitro and in vivo.

In human malignant mesothelioma cell lines an elevation of the expression of the genes for the PDGF A-chain, PDGF B-chain, and PDGF beta-receptor was found compared to normal mesothelial cells. As ovarian epithelial tumors originate from the ovarian surface epithelium, which is of mesothelial origin, we investigated PDGF chain and PDGF receptor mRNA expression in six human ovarian cell lines of epithelial origin and a granulosa tumor cell line. All six investigated ovarian epithelial tumor cell lines expressed the PDGF A- and B-chain genes, while the granulosa tumor cell line expressed the PDGF A-chain gene only. Expression of PDGF receptors was not found in the epithelial or granulosa tumor cell lines. Cytogenetic and molecular biological studies did not provide evidence for rearrangement or genomic amplification of the PDGF B-chain. Expression of PDGF was also demonstrated in ovarian tumors in vivo. Frozen sections of six serous ovarian carcinomas stained positive with an antibody against PDGF and negative with antibodies against the PDGF alpha- and beta-receptors. These results suggest that PDGF expression might be a useful marker for ovarian carcinomas.

Blotting, Southern↗

PubMed1993

Human mesothelioma cells produce factors that stimulate the production of hyaluronan by mesothelial cells and fibroblasts.

The hyaluronan production by three human malignant mesothelioma cell lines and nine primary human mesothelial cell types was determined. The mesothelioma cell lines produced only minute amounts of hyaluronan (less than 0.1 microgram/10(6) cells/48 h) whereas mesothelial cells synthesized large quantities of hyaluronan (10-72 micrograms/10(6) cells/48 h). Conditioned media from the mesothelioma cell lines were investigated for their ability to stimulate hyaluronan production by fibroblasts and mesothelial cells in vitro, and in all cases stimulatory effects were found. The factor(s) in the conditioned medium of the mesothelioma cell line Mero-25 that were responsible for hyaluronan stimulation were heat stable and partially trypsin resistant. The stimulatory activity was partially inhibited by an antiserum against platelet-derived growth factor and basic fibroblast growth factor. Our data suggest that the increased hyaluronan synthesis seen in patients with mesothelioma is due to the release of factors from mesothelioma cells that stimulate other cells to produce hyaluronan.

Culture Media↗

PubMed1992

Splicing of the platelet-derived-growth-factor A-chain mRNA in human malignant mesothelioma cell lines and regulation of its expression.

Platelet-derived-growth-factor (PDGF) A-chain transcripts differing in the presence or absence of an alternative exon-derived sequence have been described. In some publications, the presence of PDGF A-chain transcripts with this exon-6-derived sequence was suggested to be tumour specific. However, in this paper it was shown by reverse-transcription polymerase-chain-reaction (PCR) analysis that both normal mesothelial cells and malignant mesothelioma cell lines predominantly express the PDGF A-chain transcript without the exon-6-derived sequence. This sequence encodes a cell-retention signal, which means that the PDGF A-chain protein is most likely to be secreted by both cell types. In cultured normal mesothelial cells, the secreted PDGF A-chain protein might be involved in autocrine growth stimulation via PDGF alpha receptors. However, human malignant mesothelioma cell lines only possess PDGF beta receptors. If this also holds true in vivo, the PDGF A-chain protein produced and secreted by malignant mesothelial cells might have a paracrine function. In a previous paper, we described elevated expression of the PDGF A-chain transcript in human malignant mesothelioma cell lines, compared to normal mesothelial cells. In this paper, the possible reason for this elevation was studied. First, alterations at the genomic level were considered, but cytogenetic and Southern-blot analysis revealed neither consistent chromosomal aberrations, amplification nor structural rearrangement of the PDGF A-chain gene in the malignant cells. Possible differences in transcription rate of the PDGF A-chain gene, and stability of the transcript between normal and malignant cells, were therefore studied. The presence of a protein-synthesis inhibitor, cycloheximide, in the culture medium did not significantly influence the PDGF A-chain mRNA level in normal mesothelial and malignant mesothelioma cell lines. Furthermore, nuclear run-off analysis showed that nuclear PDGF A-chain mRNA levels varied in both cell types to the same extent as the levels observed in Northern blots. Taken together, this suggests that increased transcription is the most probable mechanism for the elevated mRNA level of the PDGF A-chain gene in human malignant mesothelioma cell lines.

Base Sequence↗

PubMed1992

Hydrocortisone-induced increase of PDGF beta-receptor expression in a human malignant mesothelioma cell line.

The effect of hydrocortisone (HC) on PDGF beta-receptor expression was studied in the human malignant mesothelioma cell line Mero-14. HC was found to induce a time- and dose-dependent increase of PDGF beta-receptor mRNA. Nuclear run off analysis revealed that HC induced increased transcription of the PDGF beta-receptor gene. The expression of PDGF beta-receptor protein was also elevated by HC as demonstrated with an immunoblotting assay. However, the number of PDGF-BB binding sites on the cell surface of Mero-14 remained unchanged upon HC treatment. These results suggest that steroid hormones can regulate PDGF receptor expression in vivo.

Binding Sites↗

PubMed1991

Human malignant mesothelioma cell lines express PDGF beta-receptors whereas cultured normal mesothelial cells express predominantly PDGF alpha-receptors.

In human malignant mesothelioma cell lines elevated expression of the platelet-derived growth factor (PDGF) beta-chain (c-sis) gene was previously reported, while normal mesothelial cells barely express this gene. Expression of the PDGF A-chain gene was only slightly elevated in these cell lines compared with normal mesothelial cells. For a putative autocrine function of the produced PDGF, in these cells expression of PDGF receptors is a prerequisite. In this paper we report on the expression of PDGF alpha- and beta-receptors in normal and malignant mesothelial cells. Cultured normal mesothelial cells expressed PDGF alpha-receptor mRNA and protein and had weak to undetectable levels of the PDGF beta-receptor mRNA and protein. In contrast, malignant mesothelioma cell lines were found to express PDGF beta-receptor mRNA and protein, while PDGF alpha-receptor expression was not detectable by Northern blotting and immunoprecipitation. Binding experiments with [125I]-PDGF-AA and [125I] PDGF-BB to normal and malignant mesothelial cell lines confirmed these observations. These results suggest that autocrine stimulation of growth may occur both in cultured normal mesothelial cells (PDGF-AA acting via the alpha-receptor) and in malignant mesothelioma cell lines (PDGF-BB acting via the beta-receptor).

Blotting, Northern↗

PubMed1990

Cytogenetic analysis of malignant mesothelioma.

Cytogenetic analyses of 40 confirmed malignant mesotheliomas (MMs) are reported. Pleural effusion cells were studied in 90% of the cases by direct method or after culture or both. Biopsy and ascites fluid were also analyzed in some patients. A normal karyotype was found in nine cases, and complex karyotypic abnormalities were observed in 30 cases. In one case, analyzable metaphases were not obtained. The chromosomal changes were all complex and heterogeneous; no consistent presumably specific abnormality was detected. Nevertheless, two main patterns of nonrandom abnormalities were observed: 1) loss of chromosomes 4 and 22, 9p, and 3p in the most of the abnormal cases and corresponding to a hypodiploid and/or hypotetraploid modal chromosome number; and 2) gain of chromosomes 7, 5, and 20 with deletion or rearrangement of 3p as well in the hyperdiploid cases, which were a minority in our series. These findings are discussed in view of other reported cytogenetic studies of MM, asbestos exposure, and possible mechanisms of malignant transformation.

Adult↗

PubMed1990

Cytopathology of malignant mesothelioma. Reappraisal of the diagnostic value of collagen cores.

The identification of malignant mesothelial cells in cytological smears prepared from serous effusions is still hampered by the lack of features specific for mesothelial differentiation. We examined the diagnostic value of collagen cores within clusters of tumour cells in cytological smears prepared from effusions from 43 patients with malignant mesothelioma and of 62 cases of metastatic adenocarcinoma. In Giemsa-stained smears collagen cores were detected in 51% of the cases of malignant mesothelioma and in none of the smears with metastatic adenocarcinoma. Using the Azan stain, collagen cores were detected in 64% of the malignant mesotheliomas and 4% of the adenocarcinomas. Immunoelectron microscopy demonstrated that the collagen cores are largely composed of collagen type III fibrils and some elastin embedded in a homogenous extracellular matrix. It can be concluded that the presence of collagen cores within clusters of tumour cells is highly suggestive of mesothelial differentiation and a common finding in malignant mesothelioma.

Adenocarcinoma↗

PubMed1989

Characterization of three human malignant mesothelioma cell lines.

Three human malignant mesothelioma cell lines, designated Mero-14, Mero-25, and Mero-41, have been isolated from effusions and from autopsy material of confirmed cases of malignant mesothelioma. Light and electron microscopy, cytogenetics, growth requirements, and intermediate filament expression of these cell lines were studied and, where possible, compared with the original tumor material of the patient. Cytologic and ultrastructural morphology was consistent with the mesothelial nature of the cells. All cell lines displayed a hyperdiploid karyotype similar to that of the tumor cells obtained directly from the patient. All three malignant mesothelioma cell lines had marker chromosomes 1, 3, 9, and 22, as well as other markers that were occasionally present in these cell lines and in other malignant mesotheliomas studied. Growth kinetic studies in medium supplemented with epidermal growth factor (EGF) showed increased proliferation and a decreased proliferation in medium supplemented with hydrocortisone (HC) or EGF plus HC. The three malignant mesothelioma cell lines were positive for the cytokeratins 7, 8, 18, and 19 based on immunofluorescence and immunoblotting tests with chain-specific monoclonal antibodies. The characteristics of these cell lines support the assumption that Mero-14, Mero-25 and Mero-41 are derived from malignant mesotheliomas and have retained their original character.

Aged↗

PubMed1989

Establishment of human malignant mesothelioma cell lines.

Seventeen human malignant mesothelioma cell lines were isolated from 61 samples (46 effusions, 9 biopsies and 6 tumors obtained at autopsy) collected from patients with a confirmed malignant mesothelioma. The method used is given in detail. Cytogenetic analysis of growing cultures is the best indicator to determine whether the observed proliferation concerns malignant or normal mesothelial cells. The addition of epidermal growth factor (EGF) and hydrocortisone (HC), or EGF alone, to the culture medium increases the chances of successful isolation of a malignant mesothelioma cell line.

Animals↗

PubMed1989

Malignant peritoneal mesothelioma: a series of 19 cases.

The clinical data, diagnostic procedures and survival are reported in 19 cases diagnosed as malignant peritoneal mesothelioma. All patients were men and 74% had an occupational exposure to asbestos, whereas in 26% no information about asbestos exposure was available. The median interval between asbestos exposure and the diagnosis appeared to be 44.7 years (range 18-49 years). The most common presenting symptoms were abdominal pain, weight loss and dysphagia. Most patients presented with a large amount of ascites. In the majority of patients no therapy except pain relief was given and the median survival from the time of diagnosis was 6 months (range: 0-29 months). Some patients received surgery or chemotherapy, which however did not prolong survival. Only in 2 patients survival exceeded 1 year, although these patients did not receive therapy. The autopsy findings of some patients showed that there were positive abdominal lymph nodes in 2 of them, while in no case positive thoracic lymph nodes were found. The relative short survival period from the time of the first diagnosis in contrast to malignant pleural mesotheliomas is probably the reason for the absence of distant metastases. In this series only in a minority of patients cytology of the ascites was positive and often a laparotomy had to be done. Since cytologic specimens are often negative, we suggest that in patients suspected of a malignant peritoneal mesothelioma, laparoscopy with directed biopsies is the diagnostic procedure of first choice.

Adult↗

PubMed1989

Malignant pleural mesothelioma in the southwestern part of The Netherlands.

This report is the result of an analysis of the medical records of 124 patients presenting with a malignant pleural mesothelioma. Information about asbestos exposure was available in 104 of them, which appeared to be positive in 95 (91%). The median duration of exposure was 34 yrs. The median latent period was 41 yrs. The median survival was 11 months while different ways of treatment could not prolong survival. The most common radiologic findings were pleural effusions, while in some patients contralateral effusions or pleural thickening was found. Pleural plaques or asbestosis were seen in a minority of the patients. In this series a relatively high percentage of mixed type mesotheliomas was found (56%). Large biopsies will often show both epithelial and connective tissue type elements. Concerning diagnostic procedures we recommend beginning with cytology of pleural fluid, which can easily be obtained together with an Abrams biopsy. If this does not give a definite diagnosis thoracoscopy or thoracotomy will be indicated.

Aged↗

PubMed1988

Expression of c-sis (PDGF B-chain) and PDGF A-chain genes in ten human malignant mesothelioma cell lines derived from primary and metastatic tumors.

Ten human malignant mesothelioma cell lines from primary and metastatic sites were studied for the expression of c-sis (PDGF B-chain) and PDGF A-chain genes. Malignant mesothelioma cell lines expressed strongly the c-sis oncogene which is barely detectable in normal mesothelial cells. The PDGF A-chain gene expression was slightly elevated in malignant mesothelioma cell lines compared to the expression in normal mesothelial cells. Cytogenic and Southern blot analysis did not provide evidence for genomic amplification or rearrangement of the c-sis oncogene. These results suggest that malignant mesothelioma cell lines show constitutively enhanced expression of the c-sis and PDGF A-chain genes that could play a role in the etiology of this type of malignancy.

Chromosomes, Human, Pair 22↗

PubMed1986

Construction of human-mouse T cell hybrids that express human T cell-associated surface antigens and allow the chromosomal localization of these antigens.

We have constructed somatic cell hybrids between the murine T cell line BW5147 and cells from patients suffering from T cell acute lymphoblastic leukemia. The obtained hybrid clones were analyzed for expression of human T cell antigens and presence of human chromosomes. T cell hybrids derived from fusion between the BW5147 cell line and bone marrow cells from a patient with pre-T acute lymphoblastic leukemia (TdT+/HLA-DR+/Tp41+/T11+/T1-/T6-/T4-/T8-/T3-) appeared to express the human T cell antigen Tp41, which can be recognized by the monoclonal antibodies 3A1 and WT1. Although this panel of hybrid cells contained all human chromosomes, no other T cell antigens were expressed. Fusion of the BW5147 cell line with peripheral blood cells from a patient with a more mature T cell acute lymphoblastic leukemia (TdT+/HLA-DR+/Tp41+/T11+/T1+/T6-/T4+/T8+/T3-) resulted in a panel of hybrid clones that expressed not only the Tp41 antigen, but also the human T cell antigens T1 and T4; two hybrids even expressed the T3 antigen. This panel of hybrids also contained the whole human genome. The two panels of human-mouse T cell hybrids allowed us to assign the genes coding for the human T cell antigens Tp41, T1, and T4 to human chromosomes 17, 11, and 12, respectively. Furthermore, these data support our previous suggestion that the expression of human lymphoid differentiation antigens in human-mouse lymphoid hybrids is influenced by the differentiation stage of the fusion partners.

Adult↗