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Detection of Epstein-Barr virus strain variants in lymphoblastoid cell lines 'spontaneously' derived from patients with rheumatoid arthritis, infectious mononucleosis and normal controls.

'Spontaneous' lymphoblastoid cell lines (LCL) were established from patients with either rheumatoid arthritis (RA) or infectious mononucleosis (IM) or from healthy donors. Differences in Epstein-Barr virus (EBV) strains were determined by measuring the mol. wt. and expression of viral antigens in each of the LCLs. In addition to the previously reported EBV nuclear antigens, the LCLs also contained EBV-induced antigens with mol. wt. of 48K and 58K which were present in all but two of the lines. One of the differences observed between each of the groups of cell lines was their ability to produce viral antigens. Early and late antigens were identified by immunoblotting in most of the RA lines, two of the normal lines but none of the cell lines from patients with IM. Many of the IM cell lines were also found to express multiple EBNA1 antigens. The results demonstrate that a variety of wild-type EBV strains exist. However, the similarities observed in a number of the lines suggest that the diversity of strains may be limited.

Antigens, Viral↗

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↗

Inhibition of the in vitro outgrowth of Epstein-Barr virus-transformed lymphocytes by thymus-dependent lymphocytes from infectious mononucleosis patients.

Known numbers of thymus-dependent (T) lymphocytes, obtained by positive selection from the blood of acute infectious mononucleosis (IM) patients and from control donors, were added to target cultures of foetal mononuclear cells within 0-7 days of exposure of the target cells to one of a range of doses of Epstein-Barr (EB) virus. The subsequent outgrowth of virus-transformed foetal cells was markedly inhibited by the presence in the cultures of IM-derived T cells, whilst similar numbers of T cells prepared either from cord blood or from adult donors seronegative for EB virus had little or no inhibitory effect. Target foetal cells treated with papain to remove any viral envelope material remaining on the cell surface after infection, were just as sensitive as untreated cells to the addition of IM-derived T cells. It is concluded that the inhibition cannot be mediated through recognition either of viral envelope structures on the surface of infected cells or of the antigenically related virus-determined membrane antigen, MA, but must depend upon recognition of the lymphocyte-detected membrane antigen, LYDMA. The regularity with which IM-derived T cells block the outgrowth of virus-transformed foetal cells suggests that LYDMA consistently appears on the surface of infected foetal cells before the establishment of transformed foci, but is unlikely to be directly associated with the cells' existing histocompatibility antigens.

Antigens, Viral↗

An epidemiologic study of index and family infectious mononucleosis and adult Hodgkin's disease (HD): evidence for a specific association with EBV+ve HD in young adults.

Infectious mononucleosis (IM) is an established risk factor for Hodgkin's disease (HD). A substantial minority (33%) of cases of HD have Epstein-Barr virus (EBV) DNA within the malignant cells (are EBV+ve). It is unclear whether risk after IM applies specifically to EBV+ve HD. We report the results of a population-based case-control study of HD in adults (n = 408 cases of classical HD, 513 controls) aged 16-74 years; the case series included 113 EBV+ve and 243 EBV+ve HD. Analyses compared total HD, EBV+ve HD and EBV-ve HD with the controls and EBV+ve HD with EBV-ve HD cases using, mainly, logistic regression. Regression analyses were adjusted for gender, age-group and socioeconomic status, and were performed for the whole age range and separately for young (< 35 years) and old adults (> or = 35 years); formal tests of effect modification by age were included. For the young adults, reported IM in index or relative was strongly and significantly associated with EBV+ve HD when compared to controls (odds ratio [OR] = 2.94, 95% confidence interval [CI]: 1.08-7.98 and OR = 5.22, 95% CI: 2.15-12.68, respectively). These results may be interpreted as indications that late first exposure to EBV increases risk of HD, especially in young adults; this applies primarily to EBV+ve HD.

Adolescent↗

Karyotypes in infectious mononucleosis.

Using a trypsin-Giemsa banding procedure, chromosome analysis was performed on blood from 21 consecutive patients hospitalized for infectious mononucleosis. Mitoses were harvested after 2 and 24 h in vitro incubation without PHA and after 48 h with PHA. No abnormalities were seen.

Adolescent↗

Normal human serum inhibits the lymphocytotoxicity of sera from patients with infectious mononucleosis.

The inhibitory effects of normal human serum (NHS) on the lymphocytotoxic activity (LCA) of sera from patients with infectious mononucleosis (IM) were investigated. Dilution of IM serum with complement fixation diluent (CFD) caused a significant rise in LCA at 1/10 dilution (P less than 0.001) followed by a steady decline at higher dilutions. In contrast, 1/10 dilution with pooled NHS caused a gross reduction in lymphocyte killing (P less than 0.01). This reduction occurred irrespective of the order of incubation of NHS and IM serum with target lymphocytes. Pre-dilution of the NHS showed this inhibitory effect to be dose-responsive. Further characterization of the inhibitor(s) showed it to reside in the exclusion peak of Sephadex G-200, to be abolished by treatment with the sulphydryl inhibitors, 2-mercaptoethanol and iodoacetamide and to be depleted selectively by incubation with monospecific anti-IgM (but not anti-C1q or anti-alpha 2-macroglobulin). The site of the inhibitory reaction was examined by indirect immunoperoxidase staining of the lymphocyte surface with monospecific anti-IgM and peroxidase conjugated swine anti-rabbit immunoglobulin. This showed that pre-incubation of IM serum with NHS caused a significant reduction in IgM positive cells compared to that observed with IM serum diluted in CFD alone. It is concluded that certain IgM molecules, present in NHS, inhibit the complement-mediated LCA of IM sera. This inhibition occurs by fluid phase interference with surface deposition of cytotoxic IgM rather than by competitive surface binding. The presence of such serum-serum interactions emphasises the complexity of the lymphocytotoxin reaction and the need for caution in attributing abnormalities in vivo to cytotoxic phenomena measured in vitro.

Antilymphocyte Serum↗

Epstein-Barr virus-associated infectious mononucleosis and risk factor analysis for complications in hospitalized children.

The characteristics of Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM) in Chinese children are rarely reported. To evaluate the clinical presentations and risk factors for complications of EBV-associated IM in previously healthy children in Taiwan, hospitalized children with the diagnosis of IM due to EBV infection from January 1998 to December 2002 were enrolled. Patients had to fulfill the serologic criteria for the diagnosis of primary EBV infection [viral capsid antigen immunoglobulin M (IgM)-(+), viral capsid antigen IgG-(+), and anti-Epstein-Barr nuclear antigen (EBNA) antibody-(-) with exclusion of other concurrent infections or underlying diseases]. Ninety eight children were eligible, with 79% younger than 5 years old (mean, 4.0 +/- 2.3 years). The male-to-female ratio was 2:1. Nearly all patients suffered from fever (mean duration 10.3 +/- 6.0 days). Cough/rhinorrhea, tonsillopharyngitis, cervical lymphadenopathy and hepatosplenomegaly were found over half of the patients. Atypical lymphocytosis (mean, 12 +/- 13%) and elevated serum aspartate aminotransferase (AST; mean, 167 +/- 183 IU/L) and alanine aminotransferase (mean, 221 +/- 222 IU/L) were the most striking laboratory findings. Various complications, including hematologic, hepatobiliary, central nervous system, and obstructive airway problems occurred in about 20% of patients with significantly prolonged course of hospitalization. All patients recovered uneventfully under supportive and immunomodulating management. Female gender, no signs of tonsillopharyngitis, white blood cell count < or =10,000/mm3 and AST > or =150 IU/L were significant risk factors for the occurrence of complications. Clinicians should monitor such patients closely and give proper treatment to decrease possible morbidity or even mortality should complications occur.

Adolescent↗

[Trend of the CD23+ B cells in children with infectious mononucleosis caused by Epstein-Barr virus].

OBJECTIVE: Epstein-Barr virus (EBV) is a common causative agent of infectious mononucleosis (IM) and capable of efficiently immortalizing primary B cells into continuously growing lymphoblastoid cells in vitro. As B cell activation antigen, CD23 expression is induced by EBV infection of B cells and remains constitutively expressed at high levels in virtually all EBV-immortalized cells, which have been strongly linked to the development of B-cell lymphoproliferative disease and lymphoma. Whereas previous studies were performed in vivo in animals or ex vivo cultures, the present study aimed to explore the role of EBV-immortalized cells (CD23(+)/CD19(+)) in vivo analysis of children with EBV-IM. METHODS: In a prospective trial, a group of 30 patients with IM (18 boys and 12 girls) with mean age of 3.9 +/- 1.3 years (range 6 months to 8 years) were enrolled. Clinical diagnosis of IM was confirmed based on fever, lymphadenopathy, splenomegaly, lymphocytosis (> 50%), atypical lymphocytes (> 10%) in blood smears and the elevated levels of IgM antibody against EBV capsid antigen. The day of onset of fever was recognized as day 1 of illness. Blood samples taken during acute (3 - 5 days), early convalescent (about 11 - 15 days) and convalescent phase (about 30 - 45 days) were analyzed for expressions of CD19(+)/CD23(+), CD23, CD19 on peripheral blood mononuclear cells by flow cytometry (FCM) and was compared with those of control group. RESULTS: (1) The levels of CD23(+)/CD19(+) and CD23 expressions were markedly decreased in acute stage [CD23(+)/CD19(+) (2.22 +/- 1.47)%, (132 +/- 91)/mm(3); CD23 (3.12 +/- 1.88)%, (195 +/- 102)/mm(3)] and in early convalescent stage [CD23(+)/CD19(+) (4.51 +/- 2.25)%, (166 +/- 85)/mm(3); CD23 (5.55 +/- 2.76)%, (231 +/- 130)/mm(3)] in patients with IM as compared with those of the healthy controls [CD23(+)/CD19(+) (6.71 +/- 2.25)%, (215 +/- 68)/mm(3); CD23 (7.85 +/- 3.09)%, (249 +/- 86)/mm(3), respectively]. The earlier the history was, the lower the expressive levels were. The levels of CD23(+)/CD19(+) expressions returned to, but those of CD23 expressions exceeded, normal level in convalescent stage [CD23(+)/CD19(+) (6.72 +/- 2.16)%, (213 +/- 108)/mm(3); CD23 (9.46 +/- 2.73)%, (366 +/- 200)/mm(3)]. (2) There was a positive correlation in the expressions of CD23(+)/CD19(+) and CD23 among the three stages (P < 0.01). The positive correlation between the expressions of CD23(+)/CD19(+) and CD19 only occurred during acute stage (P < 0.01). There was no correlation between the expressions of CD23 and CD19 (P > 0.05). CONCLUSION: EBV-immortalized cells and CD23(+) cells were inhibited effectively during the acute and early convalescent stage of IM. With the recovery of the disease, they gradually recovered and the levels of CD23 expressions exceeded normal level in convalescent stage.

B-Lymphocytes↗

Acute cerebellar ataxia and infectious mononucleosis.

A 28-year-old man, who presented with acute cerebellar ataxia, was found to have haematological features of infectious mononucleosis. There was serological evidence of recent infection with Epstein-Barr virus. It is speculated that cerebellar dysfunction results from virus-induced inflammatory changes within the central nervous system.

Acute Disease↗

[Acute cerebellitis in infectious mononucleosis. One case (author's transl)].

A nineteen year old man present an original clinical case of acute cerebellitis in infectious mononucleosis. Eighteen months after the acute phase of the illness, there persisted a large deficit in the circulating B lymphocytes. A short review of pertinent litterature is presented and current physiopathological hypothesis are discussed. Briefly, delayed immunity and personal predisposition appear to play important etiological roles.

Adolescent↗

Infectious mononucleosis in the University Hospital of the West Indies.

The clinical features and laboratory parameters in sixteen confirmed cases of Infectious Mononucleosis (IM) seen at the University Hospital of the West Indies between 1975 and 1989 were reviewed. The common presenting features were lymphadenopathy (14/16), fever (13/16) and pharyngitis (7/16). Atypical lymphocytosis was present in 10 cases and heterophile antibodies (HA) in 9 cases. The aetiology and laboratory diagnosis of IM are briefly discussed.

Adolescent↗

[Infectious mononucleosis with skin manifestations of the Gianotti-Crosti acrosyndrome type].

A 6-year-old boy is reported with infectious mononucleosis and a monomorphous papular eruption on the face, buttocks and limbs, as described by Gianotti and Crosti. Three types of juvenile papular acrodermatitis are to be distinguished: Gianotti-Crosti's disease, the papular acrosyndrome of Gianotti-Crosti and the papular acral manifestations caused by various viral infections. But might these eruptions not rather be the cutaneous symptom of a viral affection?

Acrodermatitis↗

Central nervous system involvement in infectious mononucleosis with studies for Epstein-Barr virus.

Neurologic complications in three girls, aged four, fourteen and fifteen years, with infectious mononucleosis are reported. All three patients had meningoencephalitis, in two of them cerebellar involvement predominated, while the third patient had cerebral involvement with paresis of cerebral nerves. The diagnosis of an Epstein-Barr virus infection was established serologiccally and in the first patient also by the detection of the Epstein-Barr virus.

Adolescent↗