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[diagnosis of epstein-barr virus infection]. 19902162418
accessory signals in t-t cell interactions between antigen- and alloantigen-specific, human memory t cells generated in vitro.the potential of activated hla class ii-positive t cells as antigen-/alloantigen-presenting cells remains controversial. in our model system we use in vitro-primed, hla class ii-specific t cells of the memory t-cell phenotype, cd4+, cd29+ (4b4+), and cd45ro+ (uchl-1). we have previously shown that alloactivated, hla class ii-positive t cells (ta) are unable to stimulate proliferative responses in naive and primed allospecific t cells when 'back-stimulation' is avoided. the explanation of this fe ...19902162555
igm autoantibodies against two cellular antigens always appear in acute epstein-barr virus infection.in the course of infectious mononucleosis, igm antibodies are formed against 2 proteins present in nucleated and non-nucleated vertebrate cells. antibodies were found in sera of all patients suffering from acute epstein-barr virus infection. in 40% of the cases these antibodies are monoclonal. persons with former epstein-barr virus infection were negative. the antibodies against the 2 proteins were first detected in raji cells with an igm-specific immunofluorescence test. the proteins were demon ...19902162556
preliminary study on specificity of iga released from lymphocytes by eb virus transformation in patients with iga nephropathy.a study on the specificity of iga in the supernatant of epstein-barr virus (ebv) transformed lymphocytes obtained from patients with iga nephropathy is described. renal biopsy specimens were obtained from nine patients with iga nephropathy and nine patients with other glomerular diseases. mononuclear cells obtained from two patients with iga nephropathy and two healthy adults were transformed with ebv and the supernatant of such transformed cell culture was applied to acid (ph 3.2)-treated renal ...19902162626
western thymomas lack epstein-barr virus by southern blotting analysis and by polymerase chain reaction.the authors investigated 16 western thymomas, 9 from the united states and 7 from europe, for the presence of epstein-barr virus (ebv) dna sequences by both southern blot hybridization analysis and polymerase chain reaction using ebv-specific dna probes that detect the long internal repeat and terminal repeat regions and the ebna-1 gene. none of the 16 thymomas contained evidence of the ebv genome, even though we could detect ebv by southern blotting when ebv dna represents less than or equal to ...19902162629
visualization of single copies of the epstein-barr virus genome by in situ hybridization.conditions have been established for demonstrating small numbers of genes of the epstein-barr virus (ebv) in b-lymphoid cells by in situ hybridization using biotinylated ebv-specific dna from cloned bamhi fragments of the viral genome. single copies of ebv genomes were successfully visualized with minimal background when the probe concentration was 0.2 micrograms/ml, the dna denaturation step was performed at 100 degrees c, and the immunochemical detection system employed a three-layer peroxidas ...19902162636
viral antibodies in multiple sclerosis. a nationwide co-twin study.serum viral antibody titers against 21 viruses were studied in 19 of 23 same-sex twin pairs with multiple sclerosis derived from the finnish twin cohort. thorough neurologic examinations showed two monozygotic pairs to be concordant, whereas all dizygotic pairs were discordant. special attention was given to measles, mumps, and rubella viruses, against which the antibody levels were determined with the complement fixation, hemagglutination inhibition, hemolysis-ingel, and enzyme immunoassay meth ...19902162658
alternative splicing dictates translational start in epstein-barr virus transcripts.of the 10 viral genes known to be expressed during epstein-barr virus (ebv) latency, six encode nuclear antigens (ebnas), all of which are expressed from a long primary transcript by means of alternative splicing and alternative polyadenylation sites. the primary transcript is generated by either of two promoters which operate in a mutually exclusive fashion in different clonal cell lines. all mrnas from either promoter have exons in common from the bamhi w viral genomic fragment (the major inte ...19902162768
interleukin 2 production by a marmoset b cell line.several b cell lines constitutively secreting interleukin (il) 2 were derived from the epstein-barr virus-positive marmoset b cell line, b95-8. a representative line, krc-18, was cloned by limiting dilution and found to be 40% surface igm+, 60% cytoplasmic igm+, greater than 95% dr+, weakly tac+ and devoid of t cell, monocyte and nk cell surface antigens. supernatant from krc-18 cells supported the long-term growth of an il 2-dependent murine t cell line, ht-2, and contained 7-8 units/ml of il 2 ...19902162776
transcription, translation and secretion of both iga subclasses in polyclonally activated human lymphocytes.to analyze human iga subclass-specific mrna we have developed rna probes for quantitation of alpha 1 and alpha 2 heavy chain constant region genes by solution hybridization. under our assay conditions, we can detect as little as 3 pg of specific mrna and there is less than 2% cross-reactivity between the two iga subclasses. using this method, the relative proportions of iga1 and iga2 mrna in pokeweed mitogen (pwm)-stimulated cells were found to be 66% and 34%, respectively, while in the epstein- ...19902162779
viral infections associated with bone marrow transplantation.bone marrow transplantation is complicated by a sequential occurrence of viral infections, the predictability of which influences disease management. among these infections are herpes simplex virus, cytomegalovirus, varicella zoster virus, epstein-barr virus, respiratory viral infections, hepatitis viral infections, and gastrointestinal infections. the approach to the treatment and prevention of these infections is discussed.19902162815
expression of an exogenous interleukin 6 gene in human epstein barr virus b cells confers growth advantage and in vivo tumorigenicity.the biological role of interleukin 6 (il-6) molecules in human b cell tumorigenesis was studied by using an episomal expression vector, phebosv-il6, to introduce stably the human il-6 gene into human epstein barr virus (ebv)-transformed b lymphoblasts. the gene was present in the il-6-transfected cells in a high copy number and was efficiently expressed, resulting in the secretion of consistent levels of il-6 molecules. the constitutive expression of the il-6 gene led to an altered pattern of gr ...19902162905
establishment and characterization of two nasopharyngeal carcinoma cell lines.two human nasopharyngeal carcinoma (npc) cell lines have been established. one derived from a 64-year-old male, and the other from a 36-year-old female chinese patient living in taiwan. both were keratinizing squamous cell carcinoma in nature and designated as npc-tw039 and npc-tw076. both have been grown in culture system for more than 100 passages. single cells from both cell lines could form colonies in 0.3% soft agar. in the nude mouse transplantation experiment, both cell lines could produc ...19902162997
studies of in vitro red cell autoantibody production in normal donors and in patients with autoimmune hemolytic anemia.the in vitro production of red cell autoantibodies (rbc auabs) has been investigated for better understanding of the pathogenesis of autoimmune hemolytic anemia (aiha). peripheral blood mononuclear cells (pbmncs) were isolated and cultured for 14 days with or without added pokeweed mitogen (pwm), autologous rbcs, methyldopa, procainamide, and alpha-methylnorepinephrine. also, isolated b cells were infected with epstein-barr virus (ebv) to produce polyclonal b-cell lines. supernatants were tested ...19902163127
epstein-barr virus--determined clonality in posttransplant lymphoproliferative disease.analysis of the genomic termini of epstein-barr virus can provide valuable insight into the cofactor role of ebv in the development of b cell lymphomas and lymphoproliferative disease. we report ebv genomic findings in pathologic specimens from 10 patients who developed lymphoma or lymphoproliferative disease after renal or bone marrow transplantation. endonuclease restriction patterns of ebv genomic termini are highly variable in size in both the episomal and linear configuration. this variabil ...19902163133
cyclosporin abrogates virus-specific t-cell control of ebv-induced b-cell lymphoproliferation.renal and cardiac recipients undergoing aggressive immunosuppressive therapy with cyclosporin a have been reported to have unusually high incidences of epstein-barr virus (ebv) genome-positive lymphomas. t cells have been shown to be of critical importance in controlling the lymphoproliferative potential of the eb virus. ebv-specific t cell clones were generated in vitro by repeated antigenic restimulation in the presence of interleukin-2 (il-2). these virus-specific cells were used to study cyc ...19902163257
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 ...19902163409
burkitt's lymphoma and the role of epstein-barr virus.burkitt's lymphoma is the most common childhood cancer in africa. most prevalent in areas endemic for malaria, the disease, a malignant growth of lymphoid tissue, usually presents itself as a large tumour of the jaw. when first characterized in the 1950s, the lymphoma was thought to spread by some infectious agent. subsequent research indicates that the frequent involvement of an infectious agent is but one factor in a more complex aetiology. today, burkitt's lymphoma is considered an example of ...19902163460
lymphoepithelial carcinoma of the stomach with epstein-barr virus demonstrated by polymerase chain reaction.epstein-barr virus dna was detected by polymerase chain reaction in a paraffin-embedded block of an undifferentiated lymphoepithelial gastric carcinoma but was absent in a poorly differentiated gastric adenocarcinoma which also had pronounced lymphoid stroma. this is the first report, to our knowledge, of a lymphoepithelial carcinoma of the stomach. the association with epstein-barr virus and the distinctive histologic appearance justify the separate classification of undifferentiated lymphoepit ...19902163534
detection of epstein-barr virus genomes in archival tissues by polymerase chain reaction.we used oligonucleotide primers designed from dna sequences unique to the long internal direct repeated region of epstein-barr virus (ebv) to enzymatically amplify this segment of the ebv genome in formalin-fixed, paraffin-embedded tissues. the products amplified from ebv templates were detected by hybridization with a labeled probe specific for this highly conserved, reiterated region. epstein-barr virus-related sequences were detected in the spleen of a patient with infectious mononucleosis, i ...19902163603
detection of epstein-barr virus genome in benign polyclonal proliferative t cells of a young male patient.epstein-barr virus (ebv) dna was detected in polyclonal t cells that proliferated transiently in a 21-year-old male (referred to as h.j.) who underwent an apparently benign lymphocytosis (white blood cells, 31 x 10(6)/microl; lymphocyte, 79%) with fever, tonsillar swelling, lymphadenopathy, and hepatosplenomegaly. the symptoms and signs subsided mostly within a month of hospitalization. the major population of the lymphocytes at admission was positive for cd3, cd8 (4/8 ratio, 0.16), wt31, and dr ...19902163693
oral hairy leukoplakia in an hiv-seronegative heart transplant patient.while oral hairy leukoplakia has been observed predominantly in patients with hiv-infection at various stages, recent reports have shown that hl may also occur in patients immunosuppressed for other reasons. this report describes oral hairy leukoplakia in a heart transplant recipient with negative hiv serology. the histopathologic diagnosis of hl was confirmed by immunohistochemical detection of ebv-vca in the surface epithelium of the lesion and by negative staining electron microscopy.19902164104
antibodies to epstein-barr virus in 50 patients with thymic tumor. 19902164111
[a senile case of b-cell lymphoma with high titers of an eb virus-associated antibodies].an 83-year-old man suffering from general malaise and discomfort in the epigastrium was admitted to hospital. on testing, peripheral blood and bone marrow smears disclosed a number of abnormal lymphocytoid cells, and a ct and a linear echo scan revealed splenomegaly and a multiple intraperitoneal lymphadenopathy, although no superficial lymph nodes were palpable. further, abnormal lymphocytoid cells were positive for b1, b4, okia1, leu1, tac, anti-igm, anti-igd, and anti-lambda. thus, a diagnosi ...19902164114
[clinical approach to herpesviruses. a composite overview].this review article describes the lesions due to herpesviruses: herpes simplex, chickenpox, herpes zoster (shingles), and infections due to cytomegalovirus and epstein-barr virus. based on current literature, clinical signs, diagnostic methods and therapeutic possibilities are given for each type of infection. b virus infections of humans are also briefly described.19902164319
identification of the cross-reactive antigens between marek's disease virus and pseudorabies virus by monoclonal antibodies.among the 33 monoclonal antibodies (mabs) against pseudorabies virus (prv) examined, three mabs (24-17, 74-26, and 8) were found to react with cells infected with marek's disease virus (mdv)-related viruses by immunofluorescence test. two of the mabs (24-17 and 74-26) reacted with the nuclei of cells infected with mdv serotype 1 (mdv1), mdv serotype 2 (mdv2), and herpesvirus of turkeys (hvt), whereas mab 8 reacted with the cytoplasm of mdv2- and hvt-infected cells. however, none of the mabs agai ...19902164393
altered immune response to glycine-rich sequences of epstein-barr nuclear antigen-1 in patients with rheumatoid arthritis and systemic lupus erythematosus.prior studies have shown that patients with rheumatoid arthritis (ra) have an increased number of circulating epstein-barr virus-infected b lymphocytes and elevated titers of antibody to epstein-barr nuclear antigen-1 (ebna-1), the major nuclear antigen expressed in latently infected b cells. however, it is not known whether antibodies from ra patients recognize the same epitopes as antibodies from normal subjects. are directed at the glycine-alanine repeating region of the molecule. antibodies ...19902164400
high-frequency transfection of cultured human epidermal basal cells that differentiate to form a multilayered tissue.primary cultures of human keratinocytes form a multilayered tissue. by incubating the tissue cultures in ca2(+)-free medium the differentiated cell layers can be stripped off leaving a basal cell monolayer. we have developed a method for high-frequency transfection of these epidermal basal cells with genes inserted into epstein-barr virus-based expression vectors. using the escherichia coli lac z gene as a marker gene, the transient and long-term expression and the fate of the transfected cells ...19902164480
the epstein-barr virus (ebv) bmrf1 promoter for early antigen (ea-d) is regulated by the ebv transactivators, brlf1 and bzlf1, in a cell-specific manner.the epstein-barr virus early antigen diffuse component (ea-d) is essential for epstein-barr virus dna polymerase activity, and its activity is suppressed during latent infection. we investigated the regulation of the promoter (bmrf1) for this early gene by studying its responsiveness in vitro to two immediate-early viral transactivators, bzlf1 (z) and brlf1 (r), focusing on the differences in response in lymphoid cells and epithelial cells. in lymphoid cells, z or r alone produced only small inc ...19902164595
[the other types of viral hepatitis].hepatitis due to viruses other than a, b, c, d, e are numerous but uncommon in adults. among the group of herpesviridae (hsv, cmv, ebv, vzv), clinical hepatitis is usually suggestive of disseminated viral infection. fulminant hepatitis occasionally observed in immunocompromised hosts are due to hsv, and vzv, but exceptionally to ebv. many new techniques using specific monoclonal antibodies permit an accurate and fast diagnosis. three drugs (vidarabine, acyclovir, ribavirine) have been shown to b ...19902164704
intrafamilial transmission of symptomatic epstein-barr virus infection among six adult members of one family.the contagiousness of epstein-barr virus (ebv) is low, and transmission of the disease from infected persons within a family or to other contacts is rare. we report of 6 adult members of 1 family who over a period of 6 months showed symptoms and laboratory findings compatible with acute ebv infection. four patients examined for ebv specific antibodies had serology typical of primary ebv infection. three of the 6 patients--1 of them serologically confirmed--were 60 years old or more, an age in wh ...19902164708
high incidence of epstein-barr virus genomes in hodgkin's disease.tissue specimens from 198 cases of hodgkin's disease and 151 non-hodgkin lymphomas, as well as 34 nonmalignant lymph node biopsies were examined for the presence of epstein-barr virus (ebv) dna by polymerase chain reaction. epstein-barr virus-specific dna sequences were detected in dna extracts from frozen and/or paraffin-embedded tissues of 58% of hodgkin's disease cases. high and low grade non-hodgkin lymphomas as well as chronic lymphocytic leukemia biopsies contained ebv dna in 26%, 14%, and ...19902164775
deficiencies of human c3 complement receptors type 1 (cr1, cd35) and type 2 (cr2, cd21).cr1 (cd35) and cr2 (cd21) are structurally related integral transmembrane glycoproteins that function as cellular receptors for human c3b and c3dg, respectively. the primary sequence of the most common structural allotype of cr1 and that of cr2 have been established, and ligand binding on the molecules has been mapped. cr1 and cr2 genes are located in close vicinity in the rca locus of chromosome 1. cr1 has a wide cellular/tissular distribution and mediates a variety of biologic functions, inclu ...19902164822
ebv and hodgkin's cells. 19902164840
specific lysis of mycobacterial antigen-bearing macrophages by class ii mhc-restricted polyclonal t cell lines in healthy donors or patients with tuberculosis.the cytolytic capacity of mycobacterial antigen-stimulated peripheral blood mononuclear cells, from healthy mantoux-positive volunteers and from patients with tuberculosis was investigated. polyclonal t cell lines induced by 7 days of stimulation in vitro with ppd or a sonicate of mycobacterium tuberculosis lysed both autologous macrophages and epstein-barr virus (ebv) transformed b cell lines which had been pulsed with mycobacterial antigens, to a greater extent than unpulsed target cells or ta ...19902164902
cd4+ cytolytic t cell clones that recognize polymorphism of hla-dr beta 3 chains.we have investigated hla-dr beta 3-associated functional polymorphism using selected epstein-barr virus (ebv) specific human t cell clones and ebv-transformed b cell (ebv-b) lines. to study the relationship between t cell recognition and the gene products of the three alleles of the dr beta 3 locus, dw24, 25 and 26 (these were previously called drw52a, b and c, respectively), cd4+ cytolytic t cell clones (cd4+ ctl) were isolated by repeated stimulation of peripheral blood mononuclear cells (hla ...19902164903
cell surface alteration in epstein-barr virus-transformed cells from patients with extreme insulin resistance.an abnormality was detected in the morphology of the cell surface of epstein-barr virus-transformed lymphocytes of patients with genetic forms of insulin resistance. in cells from two patients with leprechaunism and two patients with type a extreme insulin resistance, scanning electron microscopy demonstrated a decrease in the percentage of the cell surface occupied by microvilli in cells from the patients with leprechaunism and type a insulin resistance compared with control cells. when cells f ...19902165004
a monoclonal antibody that neutralizes epstein-barr virus dna polymerase activity.an epstein-barr virus (ebv) specific monoclonal antibody (mab), designated 55h3, was produced after immunizing balb/c mice with 12-o-tetradecanoylphorbol-13-acetate (tpa) activated b95-8 cells. it was possible to demonstrate that this mab detected an ebv-specific antigen(s) in the ebv genome-positive producer cell lines b95-8 and m-aba by immunofluorescence. immunoglobulin prepared from ascites fluid neutralized the activity of the ebv-encoded dna polymerase, but not the alkaline dnase. by weste ...19902165046
production of human monoclonal igg antibodies reacting with cytomegalovirus (cmv).a human monoclonal antibody (moab) reacting with cytomegalovirus (cmv) has been produced using somatic cell hybridization between epstein-barr virus (ebv) infected b lymphocytes and a human-mouse heteromyeloma cell line (shm-d33). the hybrids were selected in hat medium containing 5 x 10(-7) ouabain. the median level of ig production was 5 (0.1-20) micrograms/10(6) cells/day. one selected hybridoma (ib-8e9h5) has been maintained in continuous culture for more than 30 months with a stable igg2, l ...19902165098
different epstein-barr virus-b cell interactions in phenotypically distinct clones of a burkitt's lymphoma cell line.epstein-barr virus (ebv)-positive burkitt's lymphoma (bl) biopsy cells and early passage bl cell lines have been reported as showing an unusual type of virus-cell interaction; at least two ebv latent proteins appear not to be expressed. serial passage of such lines is often accompanied by a broadening of virus latent gene expression and a corresponding change in the cell surface/growth phenotype towards that shown by in vitro transformed lymphoblastoid cell lines (lcls). the sequence of events, ...19902165133
immunohistologic identification of epstein-barr virus-induced hepatitis reactivation after okt-3 therapy following orthotopic liver transplant.reactivated epstein-barr virus infection associated with hepatitis appeared in a liver transplant patient receiving monoclonal okt-3 antibody for rejection. the histologic findings in liver biopsy specimens characteristic of allograft rejection were observed prior to and during the initial phase of antirejection therapy. however, failure of a complete response to antirejection therapy promoted rebiopsy. the specimen showed portal infiltrates composed predominantly of plasma cells and immunoblast ...19902165351
influence of chain length of pyrene fatty acids on their uptake and metabolism by epstein-barr-virus-transformed lymphoid cell lines from a patient with multisystemic lipid storage myopathy and from control subjects.the uptake and intracellular metabolism of 4-(1-pyrene)butanoic acid (p4), 10-(1-pyrene)decanoic acid (p10) and 12-(1-pyrene)dodecanoic acid (p12) were investigated in cultured lymphoid cell lines from normal individuals and from a patient with multisystemic lipid storage myopathy (mlsm). the cellular uptake was shown to be dependent on the fatty-acid chain length, but no significant difference in the uptake of pyrene fatty acids was observed between mlsm and control lymphoid cells. after incuba ...19902165389
association of epstein-barr virus with polymorphic reticulosis.we report a case of polymorphic reticulosis (pr) associated with pharyngeal replication of epstein-barr virus (ebv). a 78-year-old man with necrotic inflammatory granulations in the nasal cavities and ulcerative tissue of the tonsils was found to have pr after an initial diagnosis of lethal midline granuloma and was found to have high antibody titers to ebv. ebv-determined nuclear antigen (ebna) was demonstrated in pharyngeal biopsy specimens by the anti-complement immunofluorescent technique, f ...19902165414
[the determination of the level of antibodies to epstein-barr virus antigens in organizing groups at high risk for lung cancer disease].titers of antibodies against epstein-barr virus (ebv) antigen were measured in 450 subjects aged 40 years and older. the group included patients with lung cancer, cases of non-specific chronic lung pathology and healthy subjects (150 persons in each subset). a significant increase in the level of antibodies to capsid ebv antigen was established in patients with lung cancer and chronic non-specific lung pathology as compared to healthy controls. parameters of specific immunologic response to epst ...19902165702
severe chronic active epstein-barr virus infection syndrome and adenovirus type-2 infection.four patients from 4 to 24 years of age (3 males, 1 female) with generalized lymphadenopathy, hepatosplenomegaly, and intermittent fever associated with chronic active epstein-barr virus (ebv) infection were investigated. laboratory data showed polyclonal gammopathy and a tendency for bone marrow suppression. noteworthy were the extremely elevated immunoglobulin g (igg) antibody titers to epstein-barr viral capsid antigen (vca) (range, 10,240-81,920) and early antigen (ea) (range, 1,280-40,960). ...19902165745
epstein-barr virus infection in chediak-higashi syndrome mimicking acute lymphocytic leukemia.we have had the opportunity to study a case of chediak-higashi syndrome (chs) in the accelerated phase that was associated with epstein-barr virus (ebv) infection. the clinical course of a 12-year-old boy was characterized by fever, lymphadenopathy, hepatosplenomegaly, and pancytopenia. however, in the terminal stage, the appearance of an atypical lymphoblastic leukocytosis was morphologically indistinguishable from acute lymphocytic leukemia, accompanied by benign histiocytosis with hemophagocy ...19902165746
stress-induced modulation of the immune response. 19902165759
a potential for mutual regulation of proopiomelanocortin gene and epstein-barr virus expression in human lymphocytes. 19902165763
other common types of viral hepatitis and exotic infections.this chapter discusses two distinct sets of viruses which cause hepatitis. the first include common virus infections which cause mild hepatitis rarely in individuals with normal immunity but which may cause severe life-threatening hepatitis in the increasing number of patients with depressed cell mediated immune responses. the second comprise exotic virus infections which are prevalent in particular geographical areas and which frequently involve the liver with high mortality. for each of these ...19902165845
tumor-promoting activity of staurosporine, a protein kinase inhibitor on mouse skin.staurosporine, which is a potent inhibitor of protein kinases, such as protein kinase c, inhibited both inductions of adhesion of human promyelocytic leukemia cells (50% effective dose = 9.0 nm) and epstein-barr virus early antigen in raji cells (50% effective dose = 3.4 nm) by teleocidin. however, staurosporine induced irritation on mouse ear and histidine decarboxylase activity in mouse skin. it did not induce ornithine decarboxylase activity in mouse epidermis. the two-stage carcinogenesis ex ...19902165851
classification of patients with common variable immunodeficiency by b cell secretion of igm and igg in response to anti-igm and interleukin-2.we have classified patients with common variable immunodeficiency (cvi) on the basis of the ability of their b cells to respond to anti-igm and interleukin (il)-2 in vitro. group a had cells unable to secrete igm or igg, group b secreted igm alone, and group c secreted both igm and igg. a separate small group of patients lacked peripheral b cells. where ig secretion was present with anti-igm and il-2, ebv increased it, but where it was absent, ebv only induced igm secretion in two out of eight g ...19902165880
the antiperinuclear factor. ii. variability of the perinuclear antigen.since the antiperinuclear factor (apf) test on human buccal cells is rather unpredictable, we have investigated the possible factors determining the expression of appropriate antigens by the cells. we failed to find any relationship of the expression of perinuclear antigens to the donor's smoking habits, the degree of contamination with saprophytic bacteria, the presence or absence of blood group substances in saliva, or the titers of serum antibodies to epstein-barr virus. family studies were a ...19902165883
immunologic abnormalities in chronic fatigue syndrome.the chronic fatigue syndrome (cfs), formerly known as chronic epstein-barr virus syndrome, is a clinical state of some complexity and uncertain etiology. in order to characterize in a comprehensive manner the status of laboratory markers associated with cellular immune function in patients with this syndrome, 30 patients with clinically defined cfs were studied. all of the subjects were found to have multiple abnormalities in these markers. the most consistent immunological abnormality detected ...19902166084
[cyclic neutropenia complicated of non-hodgkin lymphoma].this paper reports a case of non-hodgkin's lymphoma concurrent with cyclic neutropenia. a 59-year-old man who exhibited a neutropenia at a periodicity of 14-20 days from july 1986 was diagnosed as having cyclic neutropenia, and was re-admitted to our hospital because of an abdominal tumor in april 1988. gastroscopy revealed a borrmann ii-like elevated lesion, and abdominal ct scanning showed a low density area in the liver and swelling of the para-aortic lymph nodes. according to histological ex ...19902166174
[identification of human herpesvirus hhv-6 sequence in a case of hodgkin's disease by polymerase chain reaction].in the last decades new approaches to the diagnosis and treatment of hodgkin's disease (hd) have contributed to improved rates of survival and cure but the pathogenesis of the disease still remains unknown. data have been collected suggesting a relationship between viral infections and hd. hd patients with evidence of epstein-barr virus genomes in their affected tissues have been recently reported. human herpes virus six (hhv-6) is a newly isolated virus, derived from patients with lymphoprolife ...19902166207
in vitro analysis of epstein-barr virus: host balance in patients with acute plasmodium falciparum malaria. i. defective t-cell control.peripheral blood lymphocytes from healthy, epstein-barr virus (eb-virus)-seropositive donors and from patients with acute plasmodium falciparum malaria were tested for their cytotoxicity towards autologous eb-virus-infected b-cells using an in vitro regression assay. of the 18 cultures from control donors, 88.8% showed the normal pattern of regression. of the 20 malaria patients in the study, 40% failed to exhibit the normal pattern observed in the control group. analysis of the lymphocyte subse ...19902166284
possible role of epstein-barr virus infection in cutaneous t-cell lymphomas.although cutaneous t-cell lymphoma (ctcl) is a neoplastic helper t-cell disorder of unknown etiology, prolonged antigenic stimulation has been postulated to contribute to the development of this disease. because epstein-barr virus (ebv) infection has been associated with several different lymphomas, the sera of 21 ctcl patients were examined for antibodies to ebv antigens. by using complement immunofluorescence (cif) techniques, 13 of 21 ctcl patients had detectable antibodies to epstein-barr nu ...19902166768
epstein-barr virus types 1 and 2 differ in their ebna-3a, ebna-3b, and ebna-3c genes.the two epstein-barr virus (ebv) types, ebv-1 and ebv-2, are known to differ in their ebna-2 genes, which are 64 and 53% identical in their nucleotide and predicted amino acid sequences, respectively. restriction endonuclease maps and serologic analyses detect few other differences between ebv-1 and ebv-2 except in the ebna-3 gene family. we determined the dna sequence of the ag876 ebv-2 ebna-3 coding region and have compared it with known b95-8 ebv-1 ebna-3 sequences to delineate the extent of ...19902166806
contrasts in codon usage of latent versus productive genes of epstein-barr virus: data and hypotheses.epstein-barr virus (ebv) has two different modes of existence: latent and productive. there are eight known genes expressed during latency (and hardly at all during the productive phase) and about 70 other ("productive") genes. it is shown that the ebv genes known to be expressed during latency display codon usage strikingly different from that of genes that are expressed during lytic growth. in particular, the percentage of s3 (g or c in codon site 3) is persistently lower (about 20%) in all la ...19902166815
epstein-barr virus bzlf1 trans activator induces the promoter of a cellular cognate gene, c-fos.the epstein-barr virus bzlf1 gene product zebra is a dna-binding protein that is partially homologous to c-fos, binds specifically to ap-1 sites, and can induce the lytic cycle in latently infected b lymphocytes. induction of the viral lytic cycle can also be achieved by treatment with the phorbol ester 12-o-tetrade-canoylphorbol-13-acetate, a reagent which activates gene expression in part through ap-1 (jun/fos). in this article the interrelationship between zebra and ap-1 is extended by the de ...19902166830
cycling of cell-surface mhc glycoproteins through primaquine-sensitive intracellular compartments.class ii major histocompatibility complex (mhc) glycoproteins associate with peptides derived from material endocytosed by antigen-presenting cells and processed along the endocytotic pathway. no consensus exists as to what extent class ii molecules themselves are endocytosed and it is not known whether endocytosed mhc class ii molecules can be recycled again to the cell surface--an itinerary which might allow a single cell-surface mhc molecule to associate with different peptides during its lif ...19902166918
hot spot mutations in adenosine deaminase deficiency.we have previously characterized mutant adenosine deaminase (ada; adenosine aminohydrolase, ec 3.5.4.4) enzymes in seven children with partial ada deficiency. six children shared common origins, suggesting a common progenitor. however, we found evidence for multiple phenotypically different mutant enzymes. we hypothesized that many of the mutations would be at cpg dinucleotides, hot spots at which spontaneous deamination of 5-methylcytosine results in c to t or g to a transitions. digestion of d ...19902166947
the pathogenesis of burkitt's lymphoma. 19902166998
nucleotide sequence of a 3.5 kilobase fragment of malignant catarrhal fever virus strain wc11.a 3.5 kilobase dna fragment of the malignant catarrhal fever virus (mcfv), strain wc11, was mapped with a number of restriction enzymes, subcloned and sequenced. the fragment was subcloned into plasmid vector, puc19, for direct sequencing. a complete open reading frame of 2,058 base pairs and a partial open reading frame of 630 base pairs were identified. the sequence of 3,389 nucleotides was compared to other herpesviruses. a 310 base pairs sequence in gene a was 57% homologous to a sequence in ...19902167059
composite hodgkin's and non-hodgkin's lymphoma in a patient with acquired immune deficiency syndrome. in-situ demonstration of epstein-barr virus.a 44-year-old man infected with human immunodeficiency virus had hodgkin's disease, mixed cellularity, and malignant non-hodgkin's lymphoma, diffuse large cell type. colorimetric in-situ hybridization showed the epstein-barr virus (ebv) genome in the cells of the large cell non-hodgkin's lymphoma and in the reed-sternberg cells and reactive lymphocytes of the hodgkin's lymphoma. these results suggest that ebv may play a similar causative role in both neoplasms. this colorimetric method of hybrid ...19902167145
chromosome and gene rearrangements in immortalized human lymphocytes infected with human t-lymphotropic virus type i.karyotypes of 26 human lymphocyte cultures, infected or noninfected with human t-lymphotropic virus type i (htlv-i), with or without epstein-barr virus infection, were analyzed by g-banding. hypodiploidy and structural abnormalities were seen more frequently in htlv-i-infected cultures (30%) than in virus noninfected cultures (10%) propagated for less than 200 days. in all of six immortalized cell lines infected with htlv-i alone or with both htlv-i and epstein-barr virus, clonal chromosomal abn ...19902167166
assessment of the potential malignancy of epstein-barr virus (ebv)-infected b cells in aids-related disorders.spontaneous lymphoblastoid cell lines (lcls) were established from the peripheral blood of ten human immunodeficiency virus (hiv)-seropositive patients in order to investigate whether or not a progression of the cells toward a malignant state could be traced. the lcls studied displayed no differences in their surface phenotype, karyotype, or tumorigenicity in nude mice when compared with a wide panel of control lcls. however, four of the ten lcls derived from hiv-seropositive patients formed col ...19902167168
possible cofactors for the development of aids-related neoplasms.because of the various neoplastic manifestations of human immunodeficiency virus (hiv) and the variable period between hiv infection and the development of tumors related to acquired immunodeficiency syndrome (aids), it is possible that certain behaviors, toxins, genes, or infectious agents--particularly viruses--may act as cofactors in the pathogenesis of aids-related neoplasms. most epidemiologic and laboratory investigations of possible cofactors have been directed toward kaposi's sarcoma (ks ...19902167169
significance of viral coinfections by hiv, htlv-i, epstein-barr virus, and cytomegalovirus for immunological abnormalities in hemophiliacs.in order to clarify the influence of viral coinfection on the immunological abnormalities of hemophiliacs infected with human immunodeficiency virus (hiv), 69 patients were examined. of the 69, 35 (50.7%) were hiv-antibody positive (hiv-ab+). two of them were acquired immunodeficiency syndrome (aids) and the remaining 33 were asymptomatic carriers (ac). anti-htlv-i was found in 6 of 43 (14.3%), and 2 of these 6 were also hiv-ab+. the frequencies of positive anti-viral capsid antigen (vca) igg ag ...19902167171
detection of herpes viral genomes in normal and diseased corneal epithelium.herpetic ocular disease is one of the major causes of corneal blindness. clinical diagnosis of corneal disease is based principally on corneal appearance. however, abnormal morphology of the corneal epithelium (ce) is not an indicator for the presence of a herpes virus. further, it has not been established if herpes viruses are present in normal corneal epithelial tissue. in these studies, the polymerase chain reaction was used to evaluate normal and diseased corneal epithelium for the presence ...19902167192
ige-dependent antigen focusing by human b lymphocytes is mediated by the low-affinity receptor for ige.in this study we investigated the role of the low-affinity receptor for ige (fc epsilon rii, cd23) on epstein-barr virus (ebv)-transformed human b cells in the uptake and presentation to t cells of antigen after complexing with ige. cloned ebv-transformed b cells were incubated for 5 h with (4-hydroxy-3-iodo-5-nitrophenyl)acetyl (nip)-haptenized tetanus toxoid (nip-tt) or nip-tt complexed with a chimeric human ige/mouse anti-nip monoclonal antibody (ige x nip-tt) and then contacted for 2 min wit ...19902167225
nasopharyngeal carcinoma in children--a retrospective review and demonstration of epstein-barr viral genomes in tumor cell cytoplasm: a report of the pediatric oncology group.twenty-seven nasopharyngeal carcinomas were entered in the pediatric oncology group rare tumor registry from 1973 to 1988 (15 males, 12 females; 10 white, 15 black, two unknown; aged 8 to 17 years). eight tumors were non-keratinizing carcinomas (world health organization 2) and 19 were undifferentiated (world health organization 3). the overall 3-year survival rate was 70% (se 11%). nine children developed distant metastases and two were salvaged. we found that localized tumor (p = .02) and blac ...19902167287
coinfection with a- and b-type epstein-barr virus in human immunodeficiency virus-positive subjects.a possible cofactor in human immunodeficiency virus (hiv) infection is the epstein-barr virus (ebv), which is divided into two primary types that differ significantly in their transformation efficiency. the b-type ebv cell line is much more difficult to establish than the a-type. the extent of systemic b-type ebv infection was assessed in hiv-positive subjects and controls. lymphoblastoid cell lines were established from 26 hiv-positive subjects and analyzed for the presence of a- or b-type ebv ...19902167337
high levels of epstein-barr virus in the oropharynx: a predictor of disease progression in human immunodeficiency virus infection.the role of epstein-barr virus (ebv) on the progression of human immunodeficiency virus (hiv) infection is not well defined. the objective of this prospective study was to determine the prevalence of ebv excretion and the role that ebv might have on hiv disease progression. fifty-two homosexual males were studied, all of whom had positive ebv serology. twenty-four of the 27 hiv-seropositive and 14 of the 25 hiv-seronegative subjects had detectable levels of ebv dna in oropharyngeal cells. in add ...19902167351
[type 6 human herpes virus and chronic asthenic syndrome].chronic asthenia syndrome has been associated with epstein-barr virus (ebv). to investigate the possible role in this syndrome of human herpesvirus type 6 (hhv-6), a new herpesvirus discovered in 1986, we performed a serological study of 44 patients diagnosed of chronic asthenia syndrome and 50 controls. fifty healthy controls (34%) and 44 patients (54.5%) had positive serological tests for hhv-6. this difference was significant (p less than 0.05). the rate of positive serological studies for cm ...19902167413
virus detection by dna in situ hybridization in renal transplantation--a new perspective for differential diagnosis of virus infection versus rejection. 19902167532
interaction of epstein-barr viral (ebv) origin of replication (orip) with ebna-1 and cellular anti-ebna-1 proteins.we have previously shown that 12-o-tetradecanoylphorbol-13-acetate (tpa) which activates expression of the latent genome of the epstein-barr virus (ebv) in burkitt lymphoma cells induces the synthesis of two cellular anti-ebna-1 competitor proteins, anti-ebna-1.1 and anti-ebna-1.2. both anti-ebna-1 proteins can uncouple the specific binding of the ebna-1 to the region required for ebv plasmid maintenance (orip). here, we show by dnase i footprinting that the binding sites on orip for the ebna-1 ...19902167556
type-c virus-like particles in a human b-cell lymphoma cell line.type-c virus-like particles (vlps) were found in an epstein-barr (eb) virus-infected human b-cell lymphoma cell line, sp-50b, that was established from a patient with non-hodgkin lymphoma. the cell line continuously produces a small number of type-c vlps, 150-200 nm in diameter, over 1 year. sp-50b cells were negative for htlv-i and htlv-ii antigens and did not contain the htlv-i genome. in addition, two eb virus nuclear antigen (ebna)-positive b-cell lines, sp-54-cord and sp-57-cll, were establ ...19902167609
inhibitory effects of kampo medicine on epstein-barr virus antigen induction by tumor promoter.we have investigated the possible interaction of japanese kampo medicine; shosaiko-to with epstein-barr virus (ebv) induction by tpa (12-o-tetra-decanoyl-phorbol-13-acetate) in ebv-genome harboring cells. the effect of ether extract of shosaiko-to was also studied on the induction of ebv by superinfection with ebv from p3hr-1 cells (p3h-ebv). concomitant treatment of ebv-latently-infected cells (raji and a2l/ah) with tpa and ether extract resulted in effective inhibition of ebv-antigen induction ...19902167654
characterization of the specificity of peptide binding to four dr haplotypes.this study describes the establishment of a peptide-binding assay for purified, detergent-solubilized dr molecules. for each of the dr specificities and peptides studied, a unique pattern of interaction was observed. excellent correlation was detected between the dr1-, 2-, 5-, and 52a-binding capacities and the known dr restrictions of a panel of synthetic peptides. this supports the immunologic relevance of the binding assay, and emphasizes the importance of determinant selection in defining th ...19902167910
the nucleotide sequence of an equine herpesvirus 4 gene homologue of the herpes simplex virus 1 glycoprotein h gene.the equine herpesvirus 4 (ehv-4) gene glycoprotein h (gh) gene homologue was localized by virtue of the conserved genomic position of this gene throughout members of the herpesvirus family. the gene maps immediately downstream of the thymidine kinase gene at approximately 0.49 to 0.51 map units within genomic fragment bamh1 c. the ehv-4 gh primary translation product is predicted to be a polypeptide of mr 94,100, 855 amino acids long, which possesses features characteristic of a membrane glycopr ...19902167933
flow cytometric analysis of epstein-barr virus (ebv) latent membrane protein expression in ebv-infected raji cells.in cultures of the latently epstein-barr virus (ebv)-infected burkitt's lymphoma cell line raji, the detectable amount of the ebv-encoded latent membrane protein (lmp) is transiently increased after addition of fresh nutrient medium containing foetal calf serum. in the current study, the relative amount of lmp and dna in raji cells was determined by biparametric flow cytometry analysis at different times after the addition of fresh medium with 10% foetal calf serum to a dense raji culture. a tra ...19902167935
comparison of the classical immunofluorescent antibody tests for epstein-barr virus with commercially available test kits.twenty reference sera with previously reported titers plus 10 normal seropositive and 10 seronegative sera were used to determine which assay for the detection of antibodies to epstein-barr virus should be utilized in our laboratory. by three commercially available test systems and by slides prepared in our laboratory, all techniques detected the same number of samples positive for igg antibodies to viral capsid antigen (vca) and epstein-barr virus-determined nuclear antigen (ebna), but the geom ...19902167958
ribosome-lamella complexes observed in an epstein-barr virus-producing b-cell line, infected with human t-lymphotropic virus type i.co-cultivation of peripheral blood mononuclear cells, from a 4-year-old boy with infectious mononucleosis, with a human t lymphotrophic virus type i (htlv-i)-producing t-cell line resulted in the establishment of an htlv-i infected epstein-barr virus (ebv)-producing b-cell line. ultrastructural examination revealed the presence of ribosome-lamella complexes (rlcs), in a small proportion of long-term cultured cells. evidence is presented of continuity between rlc and the rough endoplasmic reticul ...19902167960
demonstration of epstein-barr viral dna in formalin-fixed, paraffin-embedded samples of hodgkin's disease.the presence of epstein-barr virus (ebv) dna in formalin-fixed, paraffin-embedded samples of hodgkin's disease (hd) was investigated by southern blot hybridization using a specific ebv bam h1w fragment probe. dna from 16 samples of hd in children and young adults was compared with that from ten samples in adults older than 45 years. a further eight cases of dna extracted from fresh samples of hd were also studied, in order to compare the results obtained with fresh and fixed tissue samples. hybr ...19902167963
epstein-barr virus involvement in salivary gland lesions associated with sjögren's syndrome.recently, epstein-barr virus (ebv) has gained increasing attention as a potential causative agent of sjögren's syndrome, which is an autoimmune disorder characterized by lymphocytic infiltration of salivary and lacrimal glands. to determine the association between sjögren's syndrome and ebv, we re-evaluated the salivary gland biopsies from patients previously diagnosed to have sjögren's syndrome. altogether, 20 cases of sjögren's syndrome were reviewed from the files of the university central ho ...19902168026
synthesis of digoxigenin-labelled dna probe by polymerase chain reaction: application to epstein-barr virus and chlamydia trachomatis. 19902168087
cardiomyopathy associated with nonendemic selenium deficiency in a caucasian adolescent.we describe a girl aged 17 y who died after a cardiac arrest secondary to septic shock. at autopsy, the enlarged, soft, and flabby heart showed microscopic evidence of acute myocardial infarction, myocardial edema, myocardiocyte loss, replacement fibrosis in the interventricular septum, and right and left ventricular hypertrophic nucleomegaly. the pathological diagnosis was that of cardiomyopathy due to prolonged selenium deficiency. the patient had been on total parenteral nutrition for 17 mo, ...19902168125
structures of euglobal-g1, -g2, and -g3 from eucalyptus grandis, three new inhibitors of epstein-barr virus activation.three new euglobals with acylphloroglucinol-monoterpene structures, named euglobal -g1 (1), -g2 (2), and -g3 (3) were isolated from the chloroform extract of the juvenile leaves of eucalyptus grandis (myrtaceae). the structures of these new compounds were determined on the basis of their spectral data. the compounds strongly inhibited the epstein-barr virus activation.19902168298
severe chronic ebv infection associated with specific ebv immunodeficiency and an ebna+ t-cell lymphoma containing linear, ebv dna.a patient with severe chronic epstein-barr virus (ebv) infection (cebvi) of 6 years duration developed an ebv+ t-cell lymphoma. to determine whether the development of the t-cell tumor was linked to ebv, we studied this patient's ebv-specific immune response and her t-cell tumor tissue for evidence of ebv infection. peripheral blood lymphocytes from this patient were systematically studied for immune function and response to ebv. tumor tissue was examined for ebv genome and for evidence of ebv r ...19902168301
purification of epstein-barr virus associated dnase with affinity chromatography of nasopharyngeal carcinoma patient serum.epstein-barr virus associated dnase in the homogeneous form can be purified by chromatographys using ch-sepharose 4b column conjugated with nasopharyngeal carcinoma patient serum, dna cellulose and phosphocellulose in that sequence. the molecular weight of this enzyme is shown to be 51 kilo-daltons in silver-staining and immunostains. among various methods for keeping dnase activity, the addition of bsa and dialysis in glycerol or ethylene glycol immediately after the enzyme purification is sugg ...19902168313
lymphokine-activated killer (lak) cells discriminate between epstein-barr virus (ebv)-positive burkitt's lymphoma cells.we have generated in vitro lymphokine-activated killer (lak) cells from healthy donors by stimulating their mononuclear leukocytes with recombinant interleukin-2 (ril-2) (100 u/ml). after 6 days in culture, the lytic properties of the lak cells were analyzed in the 51cr-release assay by utilizing a target panel of 6 paired lines consisting of an epstein-barr virus (ebv)-positive burkitt's lymphoma (bl) cell line and an ebv-transformed lymphoblastoid cell line (lcl) from the same donor, the raji ...19902168343
construction of human monoclonal antibodies against rabies ns-protein antigen by epstein-barr virus transformation.a human monoclonal antibody against rabies ns-protein was developed using peripheral blood lymphocytes. a special immunization protocol was used in order to achieve maximal cell numbers of active secreting b cells. these b cells were subjected to epstein-barr virus transformation and the transformed cells were cloned stepwise by limiting dilution using supernatant of stimulated macrophages. active anti-rabies-igg secreting cell clones were adapted to serum-free conditions producing stably for mo ...19902168706
enhanced ptosis in fisher's syndrome after epstein-barr virus infection.a 20-year-old woman presented with bilateral ptosis, total ophthalmoplegia, cerebellar symptoms, and hyporeflexia, indicating fisher's syndrome. she had been diagnosed with infectious mononucleosis 2 months previously. increased epstein-barr virus (ebv) titer was noted, and the epstein-barr virus-associated nuclear antigen (ebna) became positive during the clinical course. apparent light-near dissociation of the pupils was noted and accommodation was intact. during pharmacological tests with top ...19902168901
oral hairy leukoplakia.oral hairy leukoplakia, usually observed on the lateral border of the tongue, may herald the development of symptomatic human immunodeficiency virus infection. this paper reviews the pertinent clinical features and differential diagnosis, histology, methods of establishing a definitive diagnosis, and management of the patient with this epstein-barr virus-associated lesion.19902168906
ebna size polymorphism can be used to trace epstein-barr virus spread within families.the epstein-barr virus (ebv)-determined nuclear antigens ebna 1, 2, 3, 4, and 6, regularly expressed in ebv-transformed lymphoblastoid cell lines, vary in size among viral strains. we have used this characteristic to trace the spread of the virus within seven families by using an approach called ebnotyping. among 33 evaluable individuals, 3 were ebv seronegative, and 17 different ebv strains could be isolated from the peripheral blood or throat washes of the remaining 30. all unrelated persons c ...19902168960
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 ...19902168978
[subclinical course of epstein-barr virus infection in infants with transient hepatitis].epstein-barr-virus-(ebv)-infections are well known to cause acute infectious mononucleosis in adolescents and young adults. however in early infancy and childhood these infections are usually mild and clinically inapparent. in the following we describe a case of a primary ebv-infection in infancy, which led to a transient hepatitis, identified by pathologically elevated liver enzymes.19902169026
emotional repression, stress disclosure responses, and epstein-barr viral capsid antigen titers.based on the theory of psychosomatic inhibition, we hypothesized that subjects who abstained from disclosing emotional material on a laboratory task would have poorer control of latent epstein-barr virus (as evidenced by high titers for the viral capsid antigen), and similarly, those subjects with psychometrically derived repressive interpersonal styles would show the highest epstein-barr viral capsid antigen titers (ebv-vca). eighty first-year undergraduates completed a personality inventory an ...19902169064
detection of human papillomavirus and epstein-barr virus dna sequences in oral mucosa of hiv-infected patients by the polymerase chain reaction.the presence of human papillomavirus (hpv) and epstein-barr virus (ebv) was analyzed in 21 oral biopsy specimens of hiv-infected patients using the polymerase chain reaction (pcr) method. biopsies were categorized as hairy leukoplakia (hl) (n = 12), candidiasis (n = 3), oral warts (n = 2), and clinically normal epithelium (n = 4). for hpv detection a modified general primer-mediated pcr method (gp-pcr), which detects a broad spectrum of hpv genotypes at sub-picogram levels, was used. human papil ...19902169191
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