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Biomedical subjects

N Raab-Traub

Publications and source records attributed to N Raab-Traub.

At least 73 records · Page 4Linked to original sources
PubMed1991

Expression of the Epstein-Barr virus BamHI A fragment in nasopharyngeal carcinoma: evidence for a viral protein expressed in vivo.

A family of mRNAs that are transcribed rightward through the BamHI A fragment have been detected in C15, a nasopharyngeal carcinoma (NPC) which has been passaged in nude mice. Northern (RNA) blot hybridizations indicate that these RNAs are also expressed in three other NPCs which have been established in nude mice and in an NPC obtained at biopsy. Moreover, hybridization in situ detected transcription from BamHI A in 12 NPCs and 1 Epstein-Barr virus (EBV)-containing carcinoma of the parotid gland. In each case, transcription was detected in all of the malignant epithelial cells. Transcription was not detected in two cases of EBV-positive lymphoma biopsies by in situ hybridization nor in latently infected EBV-positive lymphoblastoid cell lines by Northern blot hybridization. The consistent transcription of these sequences in latently infected epithelial malignancy but not in lymphoid cells suggests that this viral function is associated with latent EBV infection of epithelial cells. Sequence analysis of a cDNA synthesized from the C15 tumor, representing the 3' end of BamHI A messenger RNA, revealed an open reading frame (ORF). Translation of this ORF in vitro produced several peptides that were immunoprecipitated with antisera from patients with NPC. The detection of antibodies to the protein encoded by the ORF present in the BamHI A cDNA indicates that BamHI A encodes a protein which is expressed in vivo and is antigenic.

Animals↗
PubMed1991

Epstein-Barr virus infection in carcinoma of the salivary gland.

Undifferentiated carcinoma of the parotid gland contains clonal Epstein-Barr virus episomes without ladder arrays of restriction enzyme fragments representing virion DNA. Analysis of Epstein-Barr virus transcription in situ in parotid carcinoma specimens revealed that the EBER RNAs, latent membrane protein mRNA, and the BamHI-A rightward reading frame, BARF0, are expressed in the malignant epithelial cells.

Alaska↗
PubMed1991

Epstein-Barr virus and malignant lymphoepithelial lesions of the salivary gland.

This report describes the results of histopathologic and virologic studies in six patients with undifferentiated carcinoma (malignant lymphoepithelial lesions) of the salivary glands. Epstein-Barr virus (EBV) was detected in tumors from all six patients by DNA hybridization, while adjacent non-tumorous salivary gland tissue was negative for EBV in two patients tested for DNA and in three patients tested for Epstein-Barr nuclear antigen (EBNA). These findings add more evidence that these unusual salivary gland tumors are EBV-associated, and that EBV is specific to the tumor.

Adolescent↗
PubMed1991

Establishment and characterization of an Epstein-Barr virus spontaneously transformed lymphocytic cell line derived from a hairy cell leukemia patient.

Hairy cell leukemia is a rare, B-cell malignancy uniquely sensitive to the antitumor effects of alpha and beta interferons (IFN). In order to further study the effects of IFN in this disease, we derived a cell line (HC1) from the peripheral blood mononuclear cells of a patient with hairy cell leukemia (HCL). Cells exhibited the typical morphological features of HCL, including the characteristic cytoplasmic projections by light, transmission, and scanning electron microscopy. HC1 cells were of B-cell lineage, as evidenced by immunophenotypic analysis. Although originally TRAP positive, HC1 cells lost this biochemical marker following 3 months in culture. Monoclonality of the cell line was confirmed by a clonal karyotypic abnormality characteristic of B-cell malignancies, and the presence of a single, distinctive fused terminal EBV fragment. The cells formed colonies in soft agar and were tumorigenic in irradiated nude mice. HC1 cells were sensitive to the antiproliferative effects of IFN-a and IFN-beta, but only moderately sensitive to the growth inhibitory effects of IFN-gamma. Incubating the cells in the presence of Type 1 IFN resulted in stabilization of cell numbers, without cellular proliferation or loss. Cell cycle analysis revealed that IFN-alpha resulted in a build-up of cells in the S phase of the cell cycle, suggesting a cytostatic effect of IFN on the growth of these cells. The HC1 cell line provides a model system which will be useful for in vitro studies of the biology and treatment of this disease.

Animals↗
PubMed1990

Oral hairy leukoplakia.

Oral hairy leukoplakia occurs almost exclusively in human immunodeficiency virus (HIV)-infected patients and is predictive for the development of acquired immunodeficiency syndrome (AIDS). It presents as a white plaque with a rough surface, most commonly on the sides of the tongue. The eruption is frequently overlooked, and, because it is commonly mistaken for oral candidiasis, its true incidence is unknown. The leukoplakia is the result of permissive infection of epithelial cells by the Epstein-Barr virus. Antiviral therapy that inhibits Epstein-Barr virus replication can result in clinical improvement. Oral hairy leukoplakia provides a unique clinical model for investigations on the pathogenesis of Epstein-Barr virus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Epstein-Barr virus small nuclear RNAs are not expressed in permissively infected cells in AIDS-associated leukoplakia.

Epstein-Barr virus (EBV) DNA structure and gene expression were analyzed in tissue specimens from oral hairy leukoplakia (HLP), a mucocutaneous lesion that develops in patients infected with human immunodeficiency virus (HIV). The structure of the terminal restriction enzyme fragments of EBV revealed that HLP is a permissive infection without a predominant, detectable population of EBV episomal DNA. In RNA preparations from this uniquely permissive infection, EBV replicative mRNAs could be identified by Northern analysis; however, the virally encoded small nuclear RNAs, the EBERs, were not detected in most HLP RNA preparations. In situ hybridization detected EBER expression in very rare cells. These data indicate that unlike other viral small nuclear RNAs, the EBERs are not expressed during viral replication and must participate in the complex maintenance of latent EBV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Defective viral DNA in Epstein-Barr virus-associated oral hairy leukoplakia.

Defective Epstein-Barr virus (EBV) has a deleted and rearranged genome (termed het DNA) that disrupts latency and induces standard EBV to replicate in vitro. We used the polymerase chain reaction to detect, in 2 of 10 patient samples, the junction of abnormally juxtaposed EBV DNA fragments BamHI W and Z, a genomic rearrangement responsible for the biologic activity of het DNA. By sequence analysis, the junction in wild-type defective DNA appears to be similar but not identical to the recombination in the DNA of laboratory strain P3HR-1. The presence of this marker for het DNA in the epithelial lesions of two patients suggests a role for defective EBV in a human pathologic process.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Novel transcription from the Epstein-Barr virus terminal EcoRI fragment, DIJhet, in a nasopharyngeal carcinoma.

Transcription of Epstein-Barr virus (EBV) genes in epithelial tissue, one of the two principal cell types infected by EBV, is not well characterized. EBV transcription in a nasopharyngeal carcinoma established in nude mice, C15, has been analyzed by using strand-specific RNA probes and sequence analysis of a C15 cDNA library. In C15, two equally abundant mRNAs of 3.7 and 2.8 kilobases (kb) are encoded by the sequences that encode latent membrane protein (LMP). Hybridization with probes specific for the 3' end of the LMP mRNA to Northern (RNA) blots and sequence analysis of cDNAs representing the messages indicated that the 3.7- and 2.8-kb mRNAs are 3' coterminal. Sequence analysis of additional cDNAs revealed an mRNA that is spliced identically to the LMP mRNA but is initiated 5' to the promoter for LMP. A probe representing the sequences contained within the cDNA which are 5' to the LMP promoter identified the 3.7-kb mRNA in C15 and a low-abundance 3.7-kb mRNA in B95-8 RNA. These data indicate that transcription of the LMP-encoding sequences is complex and that LMP can be expressed from an additional RNA in both nasopharyngeal carcinoma and lymphoid cells. Hybridization with BamHI-A identified a predominant 4.8-kb mRNA and two less abundant larger-molecular-weight mRNAs transcribed in C15. These mRNAs are consistently expressed in all passages in nude mice of the C15 tumor. Hybridization with strand-specific probes and sequence analysis of three cDNAs revealed that these mRNAs are transcribed from left to right. Sequence analysis of cDNAs representing the 3' end of the mRNAs identified an open reading frame that could potentially encode a protein of 174 amino acids. In situ hybridization of a 35S-labeled RNA probe homologous to the BamHI-A cDNA to tissue sections revealed that the BamHI-A mRNA is not focally expressed and is transcribed in all cells within the C15 tumor. Linear forms of EBV DNA were not detected in any of the C15 tumors, and replicative viral antigens have not been detected. These data suggest that the C15 tumor represents a latently infected tumor and that the transcription from BamHI-A, which is expressed in all cells, is not associated with virus replication.

Amino Acid Sequence↗
PubMed1990

Concatameric replication of Epstein-Barr virus: structure of the termini in virus-producer and newly transformed cell lines.

The linear form of Epstein-Barr virus (EBV) DNA has homologous direct tandem repeats of approximately 500 bp at each terminus (TR). After infection, EBV DNA circularizes via the TR to form the intracellular episomal DNA. To analyze the mechanism of the synthesis of linear DNA through possible replicative intermediates, the terminal fragments were identified in the total intracellular DNA and the covalently closed circular DNA from a productively infected cell line after induction of replication or after treatment with an inhibitor of viral DNA synthesis. These studies indicate that some of the fused terminal fragments detected in the total intracellular DNA are replication-dependent forms which are selectively excluded from the covalently closed circular fraction and are eliminated after treatment with acyclovir. The EBV terminal restriction enzyme fragments were identified in three producer cell lines, each with a characteristic number of TR in the intracellular episomal DNA. Identification of the termini in cell lines established with the three virus strains revealed that the newly transformed cell lines had a greater number of TR than did the template DNA in the producer cell line. The increase in the number of TR in progeny episomes indicates that linear DNA is produced from concatameric replicative intermediates rather than from amplified catenated circular intermediates.

Cell Line↗
PubMed1989

Transforming activity of nasopharyngeal carcinoma DNA detectable in mouse JB6 cells.

A JB6 mouse epidermal recipient cell line has been used to detect nasopharyngeal carcinoma (NPC) DNA-associated transforming activity that is not detectable in the NIH 3T3 focus assay. NPC DNA showed both transforming activity and activity for transferring sensitivity to tumor-promoter-induced neoplastic transformation, assayed in 2 different variants of mouse JB6 cells. Comparison of DNAs from various NPC sources that did or did not harbor EBV DNA and that varied in degree of differentiation showed similar transforming activities and similar activities for transferring promotion sensitivity. Thus both a NPC DNA-associated promotion sensitivity and an oncogenic activity function independently of concurrent EBV gene expression.

Animals↗
PubMed1989

The human DNA tumor viruses: human papilloma virus and Epstein-Barr virus.

HPV and EBV are common infectious agents that persist after primary infection in a latent state with occasional shedding of virus. Therefore, one of the fundamental questions in the etiology of those cancers that are linked to infection with such ubiquitous viruses is why cancer develops in a few people when many are infected. Because only a small subset of infected people will develop specific cancers, it has been suggested that the presence of the viral genomes in the malignancies merely indicates a persistent or latent infection. However, if the viral infection was not an etiologic factor in the development of the specific cancers, then one would predict that the proportion of cancers that contained the viral genome would reflect the proportion of infected people and that the same cancers could develop in uninfected people. The sporadic detection from nonendemic areas of Burkitt's lymphoma without EBV initially suggested that EBV infection was not etiologic. However, the rate of incidence of BL in infected populations of children is disproportionately greater than the very low incidence in uninfected children, which suggests that EBV infection is an important contributing factor. Moreover, the development of EBV-induced lymphomas in the immunocompromised and the consistent detection of EBV in specific epithelial malignancies such as NPC suggest that EBV infection is essential in the induction of specific cancers. Similarly, the consistent detection of particular HPV types in certain types of cancer suggests that HPV is also an etiologic factor. There are several strikingly similar aspects of infection with HPV and EBV. In latent infection, both of the viral genomes persist as an extrachromosomal episome with an origin of replication that is activated by binding to a virally encoded polypeptide. The state of viral infection appears to be linked with the state of cellular differentiation such that latent infections are activated into a replicative state as the cells differentiate. Moreover, elevated levels of expression of the putative transforming genes are linked to transformation. However, perhaps most importantly, the malignancies are clonal with regard to the viral infection; HPV-associated malignancies have unique integrative events and EBV-associated malignancies have clonal episomal forms. This reveals that the specific cancers are clonal cellular proliferations that developed after viral infection. In vitro, the initially polyclonal cell lines produced by EBV infection rapidly evolve to oligoclonality or monoclonality. This could be due to a slightly faster rate of growth such that the progeny of one clone rapidly predominate.(ABSTRACT TRUNCATED AT 400 WORDS)

Burkitt Lymphoma↗
PubMed1989

Comparison of the efficacy of surgery and acyclovir therapy in oral hairy leukoplakia.

To compare the therapeutic effects of surgical excision and orally administered acyclovir therapy on symptomatic oral hairy leukoplakia, 45 homosexual men who were seropositive for human immunodeficiency virus participated in a 3-month open-label study. In the 14 patients who had surgical excision, pain resolved in four symptomatic patients and the leukoplakia did not recur in the areas of excision. New foci of leukoplakia, however, appeared in 10 patients after 3 months. Of the 16 patients who received acyclovir therapy, 12 had a clinical regression, although recurrences were noted in all patients after 3 months. Three patients had resolution of pain while taking acyclovir; in two the pain recurred after acyclovir was discontinued. No spontaneous remissions of the leukoplakia occurred in the 15 patients who refused therapy. We conclude that surgical excision is effective in patients with symptomatic oral hairy leukoplakia.

Acyclovir↗
PubMed1989

Latent and replicating forms of Epstein-Barr virus DNA in lymphomas and lymphoproliferative diseases.

Epstein-Barr virus (EBV) is associated with lymphomas and lymphoproliferative diseases that occur mainly in immunocompromised patients, but the role EBV plays in their pathogenesis is unclear. The evidence linking EBV etiologically to these disorders includes the presence of EBV DNA and nuclear antigens in the lesions and serologic evidence that some patients with these lesions are experiencing primary or reactivated EBV infections. These syndromes may represent proliferation of cells latently infected with EBV, but the possibility of viral replication has not been rigorously studied. DNA extracted from biopsies of 35 lymphoproliferative diseases was probed with regions of the EBV genome capable of distinguishing circular, episomal DNA found in latency from linear, replicating EBV DNA. All samples contained restriction fragments characteristic of fused termini, indicative of circular, latent genomes. Thirteen samples contained additional restriction fragments diagnostic of linear EBV DNA. Therefore, replicating EBV DNA is found in approximately 40% of EBV-associated lymphoproliferative disorders.

Acyclovir↗
PubMed1989

Epstein-Barr virus with transforming and early antigen-inducing ability originating from nasopharyngeal carcinoma: mapping of the viral genome.

Epstein-Barr virus (EBV) from a human hybrid epithelial cell line (NPC-KT), derived from the fusion of human adenoidal cells and EBV genome-containing primary nasopharyngeal carcinoma cells (NPC) has both transforming and early antigen (EA)-inducing abilities. EBV DNA from NPC-KT cells was partially digested with TaqI and ligated to the cloning vector pJB8 at the ClaI site. This cosmid library encompassed the whole genomic DNA of the virus except for several kb of the terminal fragments. The identification and location of each of the cloned DNA fragments have been defined by hybridization to blots prepared with B95-8 and NPC-KT virion DNA. Defective heterogeneous restriction enzyme fragments of the viral DNA were not identified in any of the cosmid clones nor detected in hybridizations to virion DNA, which indicates that a single virus population derived from the NPC tissue has both transforming and EA-inducing activities.

Antigens, Viral↗
PubMed1988

Expression of the c-fgr related transcripts in Epstein-Barr virus-associated malignancies.

The proto-oncogene c-fgr is expressed at high levels in cell lines derived from lymphomas which are infected with Epstein-Barr virus (EBV) (Cheah et al., 1986). mRNA extracted directly from biopsies of EBV-infected tissues was analyzed on Northern blots to determine if c-fgr is expressed during lympho-proliferations induced in vivo by EBV and in nasopharyngeal carcinoma (NPC), the epithelial malignancy associated with the virus. Elevated levels of c-fgr expression were detected in all EBV-positive lympho-proliferations in vivo but not in cell lines established by EBV infection in vitro. This indicates that the induction of the c-fgr proto-oncogene is not an essential component of EBV-induced transformation. Although no c-fgr expression was detected in EBV-positive or -negative epithelial cell lines, the 3.0-kb c-fgr mRNA was detected at low levels in mRNA obtained from NPC biopsy specimens. However, NPC tissue, after passage in nude mice (which eliminates infiltrating lymphoid and myeloid cells) did not contain the 3.0-kb c-fgr mRNA. The absence of expression of c-fgr in the malignant epithelial cells infected with EBV contrasts with the elevated level of the proto-oncogene in EBV-infected lymphoma tissue and cell lines established from lymphomas. This suggests differences in the expression of cellular functions in EBV-induced malignancies of these 2 distinct cell types.

Genes, Viral↗
PubMed1988

Amplification of Epstein-Barr virus (EBV) DNA by superinfection with a strain of EBV derived from nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) from a nasopharyngeal carcinoma (NPC) hybrid cell line (NPC-KT) lacking defective viral DNA molecules superinfected Raji cells and induced EBV early antigens (EA), as did virus from P3HR-1 cells, which contained defective molecules. The EBV polypeptides induced by NPC-KT appeared to be identical to those induced by P3HR-1 virus. The ability of NPC-KT virus to induce EA was enhanced more than 10-fold by treatment of superinfected cells with dimethyl sulfoxide; however, dimethyl sulfoxide treatment did not enhance superinfection by P3HR-1 virus. After infection, DNA synthesis of both the superinfecting NPC-KT virus and the resident Raji viral genome was induced. In addition to amplified Raji EBV episomal DNA, a fused terminal fragment of NPC-KT viral DNA was detected. The detection of fused terminal DNA fragments suggests that the superinfecting virion DNA either circularizes or polymerizes after superinfection and is possibly amplified through circular or concatenated replicative intermediates.

Antigens, Viral↗
PubMed1987

The differentiated form of nasopharyngeal carcinoma contains Epstein-Barr virus DNA.

Immunologic studies of Epstein-Barr virus (EBV) have implicated EBV in undifferentiated and partially differentiated, non-keratinizing nasopharyngeal carcinoma (NPC). Patients with the well-differentiated, keratinizing form of NPC have EBV serologic patterns similar to those of control populations. In addition, viral DNA has not been detected in the differentiated tumors using viral cRNA probes to DNA immobilized on filters. In this study we have tested for EBV DNA using recombinant DNA probes to Southern blots of DNA from 33 NPC specimens. The 24 undifferentiated and 4 partially differentiated specimens generally contained a relatively high number of EBV genome equivalents, while the 5 well-differentiated NPC all contained detectable EBV, but at low copy number. The viral DNA from one of the well-differentiated specimens was cloned into a cosmid vector. Five recombinant clones representing the fused viral termini were obtained, indicating the presence of episomal, intracellular DNA in the tumor. These findings indicate that all histologic subsets of NPC contain EBV DNA.

Antibodies, Viral↗