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G Pallesen

Publications and source records attributed to G Pallesen.

At least 37 records · Page 2Linked to original sources
PubMed1993

Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells.

Epstein-Barr virus (EBV) is associated with a number of different human tumors and appears to play different pathogenetic roles in each case. Thus, immunoblastic B cell lymphomas of the immunosuppressed display the full pattern of EBV latent gene expression (expressing Epstein-Barr nuclear antigen [EBNA]1, 2, 3A, 3B, 3C, and -LP, and latent membrane protein [LMP]1, 2A, and 2B), just as do B lymphoblastoid cell lines transformed by the virus in vitro. In contrast, those EBV-associated tumors with a more complex, multistep pathogenesis show more restricted patterns of viral gene expression, limited in Burkitt's lymphoma to EBNA1 only and in nasopharyngeal carcinoma (NPC) to EBNA1 and LMP1, 2A, and 2B. Recent evidence has implicated EBV in the pathogenesis of another lymphoid tumor, Hodgkin's disease (HD), where the malignant Hodgkin's and Reed-Sternberg (HRS) cells are EBV genome positive in up to 50% of cases. Here we extend preliminary results on viral gene expression in HRS cells by adopting polymerase chain reaction-based and in situ hybridization assays capable of detecting specific EBV latent transcripts diagnostic of the different possible forms of EBV latency. We show that the transcriptional program of the virus in HRS cells is similar to that seen in NPC in several respects: (a) selective expression of EBNA1 mRNA from the BamHI F promoter; (b) downregulation of the BamHI C and W promoters and their associated EBNA mRNAs; (c) expression of LMP1 and, in most cases, LMP2A and 2B transcripts; and (d) expression of the "rightward-running" BamHI A transcripts once thought to be unique to NPC. This form of latency, consistently detected in EBV-positive HD irrespective of histological subtype, implies an active role for the virus in the pathogenesis of HD and also suggests that the tumor may remain sensitive to at least certain facets of the EBV-induced cytotoxic T cell response.

Antigens, Viral↗
PubMed1993

Expression of human recombination activating genes (RAG-1 and RAG-2) in angioimmunoblastic lymphadenopathy and anaplastic large cell lymphoma of T-type.

In order to determine the genotypic maturation status of the proliferating lymphoid cells in angioimmunoblastic lymphadenopathy (AILD) and in anaplastic large cell lymphoma of T-type (T-ALC), recombinase activating gene (RAG-1 and RAG-2) expression was assessed in six AILD and five T-ALC cases using a sensitive reverse transcriptase (RT) and competitive (C) polymerase chain reaction (PCR). RAG transcripts were not detectable in nine cases with high proliferating activity, suggesting that in most cases the proliferating cells are derived from mature (rearranged) lymphocytes. However, low levels of RAG transcripts were detected in one AILD and one T-ALC case and are consistent with either an involvement of immature lymphoid precursors in the proliferating pool or a deregulated T-cell maturation pathway with persistence of RAG expression. An association between RAG gene expression and poor response to therapy is possible but has to be tested in larger prospective series.

Animals↗
PubMed1993

Heterogeneity of CD3 antigen expression in T-cell lymphoma.

CD3 antigen expression was studied in a series of 98 T-cell lymphomas, using polyclonal antibodies which recognize this molecule in routinely processed, paraffin-embedded, tissue. We identified 40 cases in which CD3 was present on only a proportion of the neoplastic cells. This phenomenon of heterogeneous CD3 expression was commonest in pleomorphic T-cell lymphomas (22/42 cases) and in CD30 (Ki-1)-positive lymphomas (5/11 cases), and was less frequently observed in mycosis fungoides (4/18 cases) and not seen in T-cell lymphoblastic lymphoma (0/9 cases). CD3 expression was often related to cell morphology, with CD3 antigen being present on the smaller neoplastic cells but absent from the larger ones. The diagnostic significance of these observations is that, on occasion, it may be possible to diagnose a lymphoma as being of T-cell origin in paraffin sections by demonstrating a minor subpopulation of CD3-positive neoplastic cells.

CD3 Complex↗
PubMed1993

Retrovirus-like particles in an Epstein-Barr virus-producing cell line derived from a patient with chronic progressive myelopathy.

A B-lymphoblastoid cell line (LCL) of polyclonal origin was isolated from a 30-year-old male patient with a chronic progressive myelopathy clinically resembling multiple sclerosis (MS). The LCL expresses Epstein-Barr virus (EBV) encoded proteins and on transmission electron microscopy (EM) the LCL was shown to produce both EBV particles and retrovirus-like particles spontaneously. The LCL was negative for human retrovirus (HIV-I and HTLV-I) sequences by polymerase chain reaction (PCR). Furthermore the patient was seronegative to these retroviruses including HTLV-II and HIV-II. We, therefore, suggest that the LCL is double-infected with EBV and a hitherto uncharacterized human retrovirus. The possible implications of these two viruses on development of diseases are discussed.

Adult↗
PubMed1993

Influence of Epstein-Barr virus encoded latent membrane protein 1 on the expression of CD23 antigen, ICAM-1 and LFA-3 in Hodgkin and Reed-Sternberg cells. A morphometric analysis.

Epstein-Barr virus (EBV) latent membrane protein 1 (LMP 1) is expressed in Hodgkin and Reed-Sternberg (HRS) cells in about one half of Hodgkin's disease (HD) cases. In vitro, LMP 1 induces B-cell expression of CD23 antigen, ICAM-1 and LFA-3. To evaluate the influence of LMP 1 on the expression of these molecules in HRS cells in vivo, we performed a quantitative frozen section immunohistological study comparing the numerical density (cells per unit area) of HRS cells expressing the CD23 antigen, ICAM-1 and LFA-3 in 14 LMP 1-positive and 13 LMP 1-negative HD cases. CD23 antigen was demonstrated in HRS cells in five LMP 1-positive and three LMP 1-negative cases (not significant). The relative density of HRS cells tended to be lower in the LMP 1-positive than in the LMP 1-negative cases, but this did not reach significance (0.2 > 2p > 0.1). All recognizable HRS cells expressed ICAM-1 and LFA-3 irrespective of LMP 1 status. We conclude that expression of CD23 antigen and LMP 1 are not coordinated in HD. Although LMP 1 may have some influence on CD23 antigen expression, it is unlikely that the latter is of importance in the putative EBV induced growth transformation of HRS cells in vivo.

Antigens, CD↗
PubMed1993

Epstein-Barr virus-latent gene expression and tumor cell phenotype in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. Correlation of lymphoma phenotype with three distinct patterns of viral latency.

We investigated 49 acquired immunodeficiency syndrome-related lymphomas (ARLs) for Epstein-Barr virus (EBV) by Southern blotting and in situ hybridization and, in positive cases, used cryostat immunohistology to compare EBV-latent gene expression (EBV encoded small RNA-1 [EBER-1], EBV nuclear antigen-2 [EBNA-2], latent membrane protein-1 [LMP-1] and host cell immunophenotype (CD11a, CD18, CD54, CD58, CD21, CD23, CD30, CD39, CDw70, immunoglobulin) patterns with those reported in other EBV infections. EBV+ immunoblast-rich/large cell ARLs (n = 22) showed three patterns of latency: broad (EBER+EBNA-2+/LMP-1+; n = 9), reminiscent of a lymphoblastoid cell line phenotype; restricted (EBER+/EBNA-2-/LMP-1-; n = 6), similar to endemic Burkitt's lymphoma; and intermediate (EBER+/EBNA-2-/LMP-1+; n = 7), a pattern rarely described in vitro but seen in certain EBV-related malignancies. EBNA-2 expression was associated with extranodal lymphomas. EBV+ Burkitt-type ARLs (n = 11) usually showed the restricted latency pattern (n = 8), but some expressed the intermediate form (n = 3). Adhesion (CD54, CD58) and activation (CD30, CD39, CDw70) molecule expression varied with morphology (immunoblast-rich/large cell versus Burkitt-type), but was not independently correlated with EBV-positivity. CD30 and LMP-1 expression were associated. ARLs show heterogeneity regarding both the presence of EBV and latency pattern. Comparison of these phenotypically distinct lymphoma groups with known forms of EBV infection provides clues to their possible pathogenesis.

Adult↗
PubMed1992

Frequent expression of Epstein-Barr virus latent membrane protein-1 in tumour cells of Hodgkin's disease in HIV-positive patients.

Epstein-Barr virus (EBV) is believed to be implicated in the aetiology of non-Hodgkin's lymphomas developing in immunodeficient individuals including AIDS patients. EBV has also been associated with Hodgkin's disease (HD), where the genomes have been demonstrated in the Hodgkin and Reed-Sternberg cells in some of the cases. Recent evidence has shown that EBV genomes are transcribed in these cells, because the EBV-encoded latent membrane protein-1 (LMP-1) can be demonstrated in the tumour cells in about half of the HD cases in HIV-negative patients using immunohistochemistry. LMP-1 is of special interest as a possible oncogenic agent because of its strong transforming capacity in vitro. In this study we have examined the expression of LMP-1 in HD of HIV-positive patients compared with HD in HIV-negative patients. We investigated 18 lymph nodes from 16 HIV-positive patients with HD (eight mixed cellularity, nine nodular sclerosis, one unclassified) using the CS.1-4 anti-LMP-1 monoclonal antibodies, which can usually be applied successfully to archival biopsy material. In each case, 50-90 per cent of the tumour cells were labelled. Staining was excellent for both fixatives used (4 per cent buffered formalin, Bouin's fluid). It is concluded that EBV-encoded LMP-1 is firmly associated with HD of HIV-positive patients. This is most conspicuous in the nodular sclerosing subtype HD in HIV-positive patients, in which 100 per cent were LMP-1 positive as compared with 32 per cent of nodular sclerosis HD in HIV-negative cases in a previously published series. This difference is statistically significant (P < 0.001). The possible biological and clinical significance of this difference should therefore be studied in larger series.

Adult↗
PubMed1992

Distribution of the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein in human tissues.

The hepatic alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor-related protein (LRP) binds and endocytoses alpha 2-macroglobulin-proteinase complexes in plasma. In addition, it binds lipoproteins, a novel 40 kDa protein, and complexes between plasminogen activators and plasminogen activator inhibitor type-1. This study shows, for the first time, the tissue distribution of alpha 2MR/LRP as determined by immunohistochemistry with specific monoclonal antibodies. The analysis revealed alpha 2MR/LRP-expression in a restricted spectrum of cell types, including neurons and astrocytes in the central nervous system, epithelial cells of the gastrointestinal tract, smooth muscle cells, fibroblasts, Leydig cells in testis, granulosa cells in ovary, and dendritic interstitial cells of kidney. Monocyte-derived cells displayed marked alpha 2MR/LRP expression in the phagocytes of liver, lung and lymphoid tissues, but no or low expression in antigen-presenting cells including Langerhans' cells of the skin. The high abundance of alpha 2MR/LRP in certain cell types of most organs suggests two main routes for alpha 2MR/LRP-mediated ligand clearance: (1) systemic removal in liver of circulating ligands, and (2) non-hepatic interstitial removal in different organs, including the brain.

Antibodies, Monoclonal↗
PubMed1992

Hodgkin's disease and Epstein-Barr virus.

Seroepidemiological and molecular biological studies have established an association of Hodgkin's disease with Epstein-Barr virus (EBV). Recently, EBV genomes and gene products, most notably the latent membrane protein (LMP), have been detected in approximately 50% of the cases. The findings suggest that EBV may contribute to the pathoetiology of a sizable proportion of Hodgkin's disease cases.

Antigens, CD↗
PubMed1992

Analysis of African Burkitt's and high-grade B cell non-Burkitt's lymphoma for Epstein-Barr virus genomes using in situ hybridization.

We investigated the association of Epstein-Barr virus (EBV) with African cases of Burkitt's lymphoma (BL) and high grade B cell non-Burkitt's lymphoma (non-BL) occurring in areas where BL is endemic. The presence of EBV genomes was analysed in 24 cases using in situ hybridization with a 35S-labelled EBV probe applied to paraffin sections. EBV DNA was detected in each of 10 cases of BL in which technically satisfactory results were obtained, the virus being homogeneously distributed in all identifiable tumour cells. Two other cases of BL could not be evaluated because of technical problems. In contrast, EBV DNA was not detected in any case of high-grade non-BL (10 centroblastic and two immunoblastic lymphomas). These results confirm previous reports of the strong association of EBV with endemic BL, but suggest that the virus is not important in the pathogenesis of other types of African high-grade B cell lymphoma from regions where BL is endemic.

Burkitt Lymphoma↗
PubMed1992

Epstein-Barr virus latent and replicative gene expression in oral hairy leukoplakia.

Oral hairy leukoplakia is an epithelial lesion of the tongue associated with productive infection by Epstein-Barr virus (EBV). However, no data concerning the pattern of EBV latent gene expression have been reported, and it remains unresolved whether true latent infection occurs in basal cell layers of oral hairy leukoplakia. We have studied six cases of oral hairy leukoplakia using monoclonal antibody immunohistology for EBV latent--EB nuclear antigen (EBNA) 1, EBNA 2 and latent membrane protein 1 (LMP 1); immediate-early (BZLF1); and replicative (EA, VCA, MA) proteins, and for the EBV-receptor (CD21 antigen). EBV DNA was demonstrated by nucleic acid in situ hybridization. Mid- to upper-zone keratinocytes contained EBV DNA and co-expressed EBNA 1, EBNA 2 (5 of 6 cases), LMP 1, BZLF1 protein, EA, VCA and MA. No EBV genome or gene expression could be demonstrated in basal or parabasal cells. Spinous keratinocytes were labelled by anti-CD21 antibodies HB5 and B2, but did not express the EBV-receptor as defined by reactivity with OKB7. The co-expression of latent and replicative infection-associated antigens is striking, indicating possible functional roles for latent proteins during the productive cycle. Our results suggest that oral hairy leukoplakia is caused by repeated direct infection of upper epithelial cells with virus from saliva or adjacent replicatively infected cells, rather than by a latent EBV infection of basal epithelial cells with a differentiation-dependent switch to productive infection as previously proposed.

Adult↗
PubMed1992

Insulin-like growth factor I in initial renal hypertrophy in potassium-depleted rats.

We investigated insulin-like growth factor I (IGF-I) in the kidney during the initial renal enlargement induced by dietary K depletion in rats. Kidney weight increase was significant after 3 days of K depletion and amounted to 29% after 7 days compared with pair-fed controls [839 +/- 34 vs. 648 +/- 17 mg (SE), P less than 0.01]. The kidney growth occurred despite almost complete arrest in body weight gain in K-depleted animals (8 +/- 3 vs. 34 +/- 4 g/7 days in controls, P less than 0.01). Whole kidney protein, RNA, and DNA estimations indicated that cellular hypertrophy during the first 4 days was followed by hyperplasia. Immunoassayable kidney IGF-I concentration increased by 106% (673 +/- 30 vs. 327 +/- 14 ng/g, P less than 0.01) in K-depleted animals 24 h after induction of K depletion, stayed elevated until day 4, and returned to control levels on day 7. After K depletion for 24 h, IGF-I immunostaining was markedly increased in the medullary parts of the collecting ducts from K-depleted animals, whereas kidney IGF-I gene expression (IGF-I mRNA) had decreased by 36%. The increase in total kidney IGF-I concentration and immunostainable IGF-I in collecting ducts in kidneys from K-depleted rats precedes the renal hypertrophy and thereby suggests a renotropic role for IGF-I. The increase in kidney IGF-I concentration is not associated with increased IGF-I mRNA levels, indicating that non-transcriptional mechanisms may be responsible for the renal IGF-I accumulation.

Animals↗
PubMed1992

A survey of Epstein-Barr virus gene expression in sporadic non-Hodgkin's lymphomas. Detection of Epstein-Barr virus in a subset of peripheral T-cell lymphomas.

This study analyzes the association of Epstein-Barr virus (EBV) with non-Hodgkin's lymphoma (NHL) arising in patients without pre-existing overt immunodeficiency. The authors examined 201 lymphomas (105 high-grade B-cell, 82 peripheral T-cell, 7 high-grade non-B-cell, non-T-cell, and 7 hairy-cell leukemia) for EBV gene expression by immunohistologic procedures using monoclonal antibodies to EBV latent, immediate early, and replicative infection antigens. Transformation-associated EBV latent membrane protein 1 (LMP 1) was detected in 13 (6%) NHL, comprising 4 (4%) high-grade B-cell, 8 (10%) peripheral T-cell, and 1 non-B-cell, non-T-cell lymphomas. Anaplastic large-cell lymphoma of T-cell type was consistently LMP 1-negative. EBV nuclear antigen 2 was demonstrated in only three (1%) cases. Induction of replication as defined by expression of the immediate early BamHI Z leftward reading frame 1 (BZLF1) protein was detected in five cases, but early (EA) and late (VCA and MA) lytic cycle antigens were only found in two cases and in one case, respectively. The presence of EBV was confirmed by in situ DNA hybridization in 9 of 11 EBV antigen-positive lymphomas. This study shows the surprisingly frequent presence of EBV in peripheral T-cell NHL in European patients without pre-existing overt immunodeficiency. Interestingly, most sporadic B-cell NHL are not associated with the virus. Furthermore, the usefulness of selected monoclonal antibodies for the routine immunohistological diagnosis of EBV infection was confirmed.

Antigens, Viral↗
PubMed1992

[The EBNA2 coding region in the viral genome of Epstein-Barr virus (EBV)-positive cases of Hodgkin's disease].

Epstein-Barr virus (EBV)-genome containing cases of Hodgkin's disease (HD) are known to express latent membrane protein (LMP) of EBV but no EBV nuclear antigen 2 (EBNA2). We investigated 35 cases of HD for the presence of EBV genome sequences to know whether EBNA2 coding region is deleted in HD. 27 cases had general EBV sequences, none had evidence of a deletion of EBNA2. 26 cases turned out to harbour EBV type 1, one case had EBV type 2. The absence of EBNA2 protein expression in HD can not be explained by a deletion of EBNA2 coding region. EBV type 1 is the prevalent subtype of EBV in our series of HD.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Immunologic observations in close relatives of two sisters with mammary Burkitt's lymphoma. Mammary Burkitt's lymphoma in sisters.

In a sibship of four sisters, two had Burkitt's lymphoma localized to the breast. Their pretreatment Epstein-Barr virus (EBV) serology were not examined. No EBV genome was demonstrated in the tumors using an in situ hybridization technique. The mother showed an abnormal antibody response to EBV infection consisting of elevated IgA and IgG antibody titers to viral capsid antigen (VCA) and high IgG antibody titer to early antigen. Furthermore, one of the two healthy sisters showed elevated IgG antibody titer to VCA. The EBV serology is mimicking the findings in female carriers of the X-linked lymphoproliferative syndrome.

Adolescent↗