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Biomedical subjects

I Ernberg

Publications and source records attributed to I Ernberg.

At least 91 records · Page 5Linked to original sources
PubMed1986

Lymphoblastoid cell lines and Burkitt-lymphoma-derived cell lines differ in the expression of a second Epstein-Barr virus encoded nuclear antigen.

Twenty-seven Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and 27 EBV-carrying Burkitt-lymphoma-derived lines were analyzed for expression of the second EBV-encoded nuclear antigen (EBNA-2) by immunoblotting and anticomplement immunofluorescence with EBNA-2-specific sera. While all lymphoblastoid cell lines expressed EBNA-2, only 10 of the 27 BL lines were EBNA-2-positive. Comparison of the EBNA-2 coding BamHI W-, Y- and H-fragments of EBV-DNA in the different cell lines by restriction enzyme analysis suggests that EBNA-2 negativity is due either to sequence diversity or to a deletion in the BamHI WYH region.

Antigens, Viral↗
PubMed1986

An Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA5) partly encoded by the transformation-associated Bam WYH region of EBV DNA: preferential expression in lymphoblastoid cell lines.

Four peptides were synthesized on the basis of amino acid sequences deduced from a highly spliced transcript encoded by the Bam W, Y, and H fragments of the Epstein-Barr virus (EBV) genome [Bodescot, M., Chambraud, J. B., Farrell, P. J. & Perricaudet, M. (1984) EMBO J. 3, 1913-1917]. Rabbit antisera against three of the four peptides identified a nuclear polypeptide that varied between 22 and 70 kDa in molecular size. Four of 20 EBV-positive human sera contained antibodies against this polypeptide. Since this is the fifth EBV-determined nuclear antigen (EBNA) discovered in growth-transformed cells, it is designated EBNA5. The antigen was detected in virus nonproducer lines (less than 0.01% EBV early antigen expression) and is thus not dependent on the viral cycle. It was differentially expressed depending on the origin of the lines. All 10 lymphoblastoid cell lines tested expressed EBNA5, but it could not be detected in 10 of 11 EBV-carrying Burkitt lymphoma lines. Infection of tonsillar lymphocytes with the B95-8 strain of EBV induced six EBNA5-specific polypeptides that varied between 41 and 70 kDa in molecular size with regular increments of 6 kDa. This may be due to the fact that the EBNA5 coding sequence includes the Bam W internal repeat. Parallel infection of the EBV-negative Burkitt lymphoma line Ramos with the same viral substrain did not induce detectable levels of EBNA5, nor was this antigen present in permanently EBV-converted Ramos sublines. These findings imply that the expression of the viral genome varies among B cells having different phenotypes.

Antibodies, Viral↗
PubMed1986

Four virally determined nuclear antigens are expressed in Epstein-Barr virus-transformed cells.

The expression of Epstein-Barr virus (EBV)-determined antigens associated with growth-transformation of B cells was studied by immunoblotting with human sera from healthy donors. Four antigens were detected in EBV-carrying cell lines and in B lymphocytes early after infection with the transforming B95-8 substrain of virus. They were not found in uninfected cells, nor could they be demonstrated with sera lacking antibodies to EBV antigens. All four antigens were nuclear. Each of them varied in size in the different cell lines. The two antigens with the lowest molecular weight were identified as EBV-determined nuclear antigens (EBNAs) 1 and 2. The two high molecular weight antigens (140-160 kDa and 150-180 kDa, respectively) were detected with 6 of 16 EBV antibody-positive sera. These proteins appeared to be antigenically unrelated to each other and to EBNAs 1 and 2 and were designated EBNAs 3 and 4. Like EBNAs 1 and 2, they bound to double- and single-stranded DNA in vitro.

Antigens, Viral↗
PubMed1986

Effect of acyclovir on infectious mononucleosis: a double-blind, placebo-controlled study.

Thirty-one patients with clinical and laboratory diagnoses of infectious mononucleosis who had had symptoms for seven or fewer days were randomized for intravenous treatment with acyclovir (10 mg/kg) or placebo at 8-hr intervals for seven days in a double-blind trial. Clinical signs and symptoms were registered, and excretion of virus in the saliva as well as antibody responses in sera and saliva were assessed before, during, and at regular intervals in the six months after treatment. Acyclovir significantly (P less than .001), but reversibly, inhibited oropharyngeal shedding of Epstein-Barr virus. The humoral and cellular immune responses, however, did not differ between the two groups; nor did the development of viral latency. There were no significant (P greater than .05) differences in individual clinical symptoms or in laboratory parameters between the two groups; however, when data concerning duration of fever, weight loss, tonsillar swelling, pharyngitis, and self-assessment by the patient were combined, a significant (P less than or equal to .01) effect of treatment with acyclovir was evident.

Acyclovir↗
PubMed1986

Acyclovir efficiently inhibits oropharyngeal excretion of Epstein-Barr virus in patients with acute infectious mononucleosis.

Shedding of Epstein-Barr virus (EBV) into saliva was studied in 31 patients with verified acute infectious mononucleosis. The patients had been randomized for intravenous treatment with acyclovir (ACV) at 10 mg/kg body weight at 8 h intervals for 7 days, or placebo, in a double-blind trial. EBV in centrifuged throat washings was detected by transformation of umbilical cord lymphocytes and by immunofluorescence staining for EBV-associated nuclear antigen in fixed cell smears. Saliva samples were obtained before and during treatment, and after 4 weeks and 6 months, respectively. ACV effectively but transiently interrupted EBV production (P less than 0.001), but virus shedding resumed at the initial level within 3 weeks of cessation of the treatment. Initially, 93.5% of the patients had detectable EBV in the saliva compared with 83% in the 4th week and 58% after 6 months.

Acute Disease↗
PubMed1986

An EBV genome carrying pre-B cell leukemia in a homosexual man with characteristic karyotype and impaired EBV-specific immunity.

A Burkitt-like lymphoma/leukemia confined to bone marrow was detected in a human T cell leukemia virus (HTLV)-III/LAV- and Epstein-Barr virus (EBV)-seropositive homosexual man. The tumor cells were EBNA-positive and contained at least 22 EBV genomes per cell. They were totally immunoglobin negative, but showed other markers for B cells detected with monoclonal antibodies. The patient had an impaired cellular immunity to EBV antigens and EBV-infected cells at diagnosis, but these reactions normalized during treatment. Cell clones derived from the bone marrow tumor in vitro also carried EBV and had six different marker chromosomes, including the typical 14q+ chromosome and a t(8 - ;8), which resulted in trisomy for the largest part of 8q. Partial trisomy for 12q was also observed. The patient completed six courses of combination chemotherapy and remains in excellent health after 34 months of follow-up.

Adult↗
PubMed1986

Evidence of tinidazole interference in the oropharyngeal inflammatory process during infectious mononucleosis.

The efficacy of tinidazole was studied in 24 patients with infectious mononucleosis (IM), 13 of whom were randomized for 5 days of tinidazole treatment and 11 for control without placebo. In judging the comparability of the 2 groups not only was the distribution of confounding factors such as age, sex or duration of symptoms before admission considered, but also the distribution of the Epstein-Barr virus (EBV) serological stage at entry. In these respects the groups were well matched. The duration of sore throat and pharyngotonsillitis after admission was significantly shorter for the patients treated with tinidazole than for the controls. Orosomucoid and lactodehydrogenase concentrations normalized more readily in IM patients with a short duration of sore throat after admission and in patients treated with tinidazole compared to those with a long duration of sore throat and to the tinidazole controls. Clinical and laboratory findings were thus parallel and showed a clinical effect of tinidazole, believed to be mediated via the well-known activity of this drug against anaerobic bacteria. The EBV serological stage of each patient at entry could not predict the duration of symptoms. The results showed that the course of the angina was not primarily dependent on the virus host interaction but probably on other factors, still unknown. One such factor could be the balance between the mucosal defence and the normal oropharyngeal microflora.

Adolescent↗
PubMed1986

Differences in EBV-specific antibody patterns at onset of infectious mononucleosis.

The EBV-specific antibody patterns of infectious mononucleosis (IM) patients were analyzed in relation to the onset of symptoms and clinical parameters during the acute phase of the disease. The antibody patterns varied considerably on admission. Three groups of patients were identified: one had not yet attained peak antibody titers, the second was at the peak and the third had passed the peak pattern. Patients with a "peak" current pattern had significantly higher lymphocyte counts, ASAT, ALAT, serum IgG and serum IgA concentrations than patients of the third group. Unexpectedly, there was no difference between the groups with regard to duration of sore throat and general malaise before admission. It thus seems that the lymphocyte proliferation during IM closely parallels the course of the EBV-specific antibody responses, whereas the onset of IM does not closely correlate to a specific stage of the antibody pattern.

Adolescent↗
PubMed1986

IgA antibodies to Epstein-Barr virus in infectious mononucleosis.

The IgA anti-EBV (Epstein-Barr virus) response during the course of IM (infectious mononucleosis) was investigated. The IgA anti-VCA (viral capsid antigen) response was found not to be restricted to the early acute phase of the EBV infection as is the IgM anti-VCA response. Some patients with normal total serum IgA levels did not respond with measurable EBV specific IgA. These patients and those with low titers of IgA anti-VCA had shorter duration of sore throat than responders with high titers indicative of a strong correlation between the IgA anti-VCA titers and the duration of sore throat. In this way the EBV specific IgA response is unique since recent observations show that local oropharyngeal symptoms during IM appear poorly synchronized with the IgM and the IgG antibody responses. As EB virus is excreted into the oropharynx during IM, antigens are available for local EBV immunization. The results of the present study imply a possible local immunization process as a positive correlation was found between serum IgA anti-VCA and total salivary IgA.

Adolescent↗
PubMed1985

Effect of cyclosporin-A (CsA) on the ability of T lymphocyte subsets to inhibit the proliferation of autologous EBV-transformed B cells.

We have analyzed the effect of Cyclosporin-A (CsA) on the in vitro suppression of Epstein-Barr virus (EBV)-induced B-cell proliferations separated on the basis of cell density. CsA abolished the growth-inhibitory capacity of high-density T cells but influenced only marginally the activity of low-density lymphocytes; this suggested that different mechanisms mediate suppression in the two subsets. Stimulation with irradiated EBV-transformed cells had a different impact on the activity of low- and high-density lymphocytes. Proliferative and cytotoxic responses were inversely correlated, i.e. high-density cells proliferated but exerted low cytotoxicity, while the lytic activity of the low-density subset was stronger in the absence of significant cell proliferation. Proliferation and generation of cytotoxicity were abrogated by CsA in both subsets. The activities could be restored by addition of exogenous IL-2, suggesting that the drug may interfere with the cascade of lymphokine--cell interactions which leads to activation of immune responses. From the analysis of athe CsA effects on the two subsets it seems that the high-density one contains specific memory T cells which are activated and proliferate upon encounter with EBV-infected cells. On the other hand, low-density lymphocytes are induced to release soluble factors with antiproliferative activity. The secretory function was resistant to the suppressive effect of CsA.

B-Lymphocytes↗
PubMed1985

Capacity of B-lymphocytic lines of diverse tumor origin to produce and respond to B-cell growth factors: a progression model for B-cell lymphomagenesis.

Human cell lines established from cases of acute lymphoblastic leukemia, lymphosarcoma, Burkitt's lymphoma and multiple myeloma and representing stages of B-lymphocyte development ranging from pre-B through to plasma cells, were assessed for their ability to produce and respond to B-cell growth factors (BCGF). All B-cell lines studied were found to be constitutive producers of a growth activity which assisted the S-phase entry of normal activated B-cells and provided growth support for lymphoblastoid cells transformed by Epstein-Barr virus. Furthermore, all lines responded by enhanced proliferation to supernatants from a BCGF-producing T-cell hybridoma. Not all lines, however, displayed autostimulation to their own supernatants and no tumor B-cell line appeared totally dependent on soluble factors for its growth. Non-tumorigenic B-cell lines, by contrast, revealed a strict dependency on homologous growth factor for their continued proliferation in suspension culture. The findings support a progression model of lymphomagenesis based upon the utilization, production and, ultimately, emancipation from growth-promoting soluble factors.

B-Lymphocytes↗
PubMed1985

Acyclovir treatment in primary Epstein-Barr virus infection. A double-blind placebo-controlled study.

Acyclovir (ACV), which effectively inhibits in vitro Epstein-Barr virus (EBV) production, was tested in 31 patients with clinical and laboratory diagnosis of infectious mononucleosis (IM) in a double-blind trial. Patients with symptoms not exceeding 7 days were randomised to intravenous ACV 10 mg/kg or placebo (PLO) treatment every 8 h for 7 days. Clinical, virological and immunological parameters were followed in each patient before, during and after treatment. There were no significant differences (p greater than 0.05) between the treatment groups for any single clinical symptom between the treatment groups. If data concerning duration of fever, weight loss, tonsillar swelling, sore throat and patient self-assessment of general health were combined, a significant effect (p less than or equal to 0.01) favouring ACV treatment was determined. ACV significantly inhibited oropharyngeal EBV shedding (p less than or equal to 0.001), but the salivary EBV titer returned within 3 weeks after cessation of treatment. Specific cellular and humoral immunity was not affected, nor was the development of virus latency.

Acyclovir↗
PubMed1984

Epstein-Barr virus (EBV)-specific cell-mediated and humoral immune responses in ataxia-telangectasia patients.

As a part of studies on cell-mediated immune (CMI) responses of immunocompromised, Epstein-Barr virus (EBV)-infected patients who can or cannot restrict the proliferation of EBV-transformed B cells, we have studied 16 Turkish patients with ataxia-telangectasia (AT). Fifteen were EBV seropositive; one was seronegative. Among the seropositives, eight had no or only low anti-EBV-determined nuclear antigen (EBNA) antibody titers, while seven had normal anti-EBNA levels. EBV-seropositive and -seronegative healthy Turkish children were used as controls. We have particularly asked the question whether low EBNA antibody titers can be correlated with the level of EBV-specific and -nonspecific cell-mediated immunity. Non-EBV-specific tests included cell count, phenotypical characterization with monoclonal antibodies, assessment of natural killer (NK)-cell activity, and ability to suppress mitogen-induced immunoglobulin production. Two EBV-specific CMI tests were used: outgrowth inhibition (OI) and leukocyte migration inhibition (LMI). The majority of the patients of the low-EBNA antibody group was IgA deficient and had high levels of alpha-fetoprotein (a-FP). Cells reacting with OKT8 monoclonal antibody predominated in both AT patient groups. In contrast, the suppressor activity was present in only a few patients and NK and interferon-activated killing (IAK) activities were normal. EBV-specific cell-mediated responses were defective in seven of eight patients in the low-anti-EBNA group and five of seven patients in the group with normal anti-EBNA titers. It is concluded that AT patients are often defective in their EBV-specific cell-mediated immune responses and with regard to their EBNA antibody levels. These defects are associated with a predominance of T cells reacting with OKT8 monoclonal antibody.

Adolescent↗
PubMed1984

Virologic, immunologic, and clinical observations on a patient during the incubation, acute, and convalescent phases of infectious mononucleosis.

One patient with infectious mononucleosis (IM) was studied from the probable time of Epstein-Barr virus (EBV) infection (38 days before the onset of clinically overt disease), during the incubation and acute phases, until 6 months after clinical remission. Analysis of spontaneous outgrowth of EBV-carrying lymphoblastoid cells, by limiting dilution on feeder layer cultures, showed that virus containing B lymphocytes are already present early during the incubation period. Also low interferon serum levels were detected early after infection, and only before the onset of clinical disease. All other studied clinical laboratory and virus-associated variables were within normal range during the incubation phase, but changed to a pattern characteristic of IM in parallel to the clinical symptoms. During the acute disease EBV-associated nuclear antigen (EBNA)-positive cells could be directly detected among the lymphocytes, and antibodies to EBV antigens appeared. Lymphocytes stained by monoclonal antibodies, detecting Ia-like determinants (activated cells) and suppressor cells, increased dramatically, in parallel to a strong increase of functional suppressor cell activity, measured by inhibition of blastogenesis and PWM-induced immunoglobulin production. During the acute phase there was also a decrease of spontaneous cytotoxicity against the NK-sensitive cell line K562, while cytotoxicity (spontaneous) against an autologous EBV-positive lymphoblastoid cell line (LCL) was detected only during this phase. These reactions correlated to the presence of blasts, and the autologous reaction was exerted mainly by Fc-receptor-negative cells. Lymphokine production in response to EBV antigens was also initiated during the acute phase. During the convalescence period the serological and cellular immune parameters adjusted to the pattern of a normal EBV-seropositive person.

Adolescent↗
PubMed1984

The effect of tinidazole on primary EBV infection and immunocompetence.

Tinidazole and metronidazole have been reported beneficial in the treatment of acute anginose infectious mononucleosis. As this disease is caused by the Epstein-Barr virus (EBV), the effect of tinidazole on EBV infection of human B-lymphocytes was investigated. Tinidazole had no effect on induction of EBV determined nuclear antigen (EBNA) or DNA synthesis, while immunoglobulin synthesis was increased in the presence of the drug. Cytotoxicity directed against EBV positive cell lines and long term T-lymphocyte mediated anti-EBV memory, were not affected by tinidazole. In view of these findings we suggest that tinidazole does not act directly on the primary EBV infection in vitro. Nor do our findings indicate any adverse effects of tinidazole on the virus-host relation.

Antigens, Viral↗
PubMed1984

Immunological characterization of Hodgkin's and non-Hodgkin's lymphoma patients with high antibody titers against Epstein-Barr virus-associated antigens.

We have studied nine Hodgkin's lymphoma (HD) and ten non-Hodgkin's lymphoma (NHL) patients with extraordinarily high anti-viral capsid antigen (VCA) titers (greater than 5120). Controls were 13 HD and 23 NHL patients with anti-VCA titers between 40 and 2560. High anti-VCA titers were present in NHL patients at the time of diagnosis or within 16 months, whereas the rise of anti-VCA titers in HD patients appeared to be a late event during the clinical course of the disease (mean time from diagnosis, 68 months). In particular, we have asked whether the exceptionally high anti-Epstein-Barr virus (EBV) titers in some HD and NHL patients can be correlated to some of the EBV-specific and -nonspecific parameters of cell-mediated immunity. The battery of non-EBV-specific immunological tests included the assessment of natural killer cell activity and the analysis of T-lymphocyte subclasses according to surface markers, together with spontaneous and mitogen-induced DNA synthesis and their helper or suppressor activity on PWM-generated immunoglobulin synthesis. Outgrowth inhibition (Ol) and leukocyte migration inhibition were used to assess EBV-specific cell-mediated immunity. The majority of the high-titer HD and NHL patients showed a drastically reduced OKT4:OKT8 ratio in their peripheral lymphocyte population. Low-titer HD and NHL patients showed no such reduction. There was no strict correlation between the number of OKT8-positive cells and suppressor activity in the functional PWM-induced immunoglobulin production test. Part of the high-titer HD patients showed defective cellular responses in the outgrowth inhibition test, directed against the proliferation of EBV-transformed (EBV-determined nuclear antigen-positive) cells. Some of them showed also a deficient leukocyte migration inhibition response to EBV-determined nuclear antigen but, interestingly, not to early antigen-VCA. In the NHL group, only one of the high-titer patients showed a similar defect. None of the low-titer HD and NHL patients showed such defects.

Adult↗