Epstein-Barr virus genotypes in AIDS-associated lymphomas are similar to those in endemic Burkitt's lymphomas.

PCR was used to screen EBV-positive lymphomas from endemic and sporadic Burkitt's lymphoma patients, including EBV-positive lymphomas derived from patients with HIV infection. Only 10% of sporadic lymphomas from either North America (1/15) or South America (2/14) were associated with the type 2 EBV strain, whereas 50% (8/16) of lymphomas from equatorial Africa and 46% (10/22) of HIV-associated lymphomas were positive for the type 2 strain. These data, in conjunction with previous reports, suggest that the proportions of strain types in Burkitt's lymphoma reflect the proportions of strain types in peripheral lymphocytes, and not simply the prevailing regional strain. The increased association of the type 2 strain in lymphocytes and lymphomas from HIV-infected individuals and from Africa may be a result of intermittent (malaria) or continuous (HIU) compromise of immune function in these populations.

Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. OBJECTIVE: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. PATIENTS AND METHODS: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. RESULTS: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). CONCLUSIONS: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).

Neutralization of Epstein-Barr virus-induced ribonucleotide reductase with antibody to the major restricted early antigen polypeptide.

A previous study had established a relationship between the major polypeptide of the Epstein-Barr Virus (EBV)-induced restricted (R) component of the early antigen (EA) complex and the large subunit of ribonucleotide reductase. This association was confirmed in this study by the observation that a monoclonal antibody prepared against the 85-kDa R component reacted in immunoblotting with the protein product (molecular weight approximately 93 kDa) encoded by the Xbal fragment of the B-95-8 strain of EBV. This fragment encodes for both the small and large subunits of this virus-induced enzyme. This size of the reactive protein indicated that it was the large subunit. Direct evidence that the 85-kDa EA-R component was associated with the viral-induced ribonucleotide reductase was provided by enzyme inhibition studies. Two monoclonal antibodies prepared against the tertiary structure of the 85-kDa EA-R antigen significantly inhibited the in vitro activity of the viral-specified enzyme but had no effect on ribonucleotide reductase activity derived from two different cellular preparations. A monoclonal antibody prepared against the denatured form of this antigen was ineffective in neutralizing the virus-specific ribonucleotide reductase as were antibodies to different EBV polypeptides. These results therefore conclusively demonstrate that the 85-kDa EA-R polypeptide is associated with the large subunit of this viral-specified enzyme and further suggest that the active site of the enzyme is associated with the tertiary structure of the large subunit.

Perspectives from the National Institute of Mental Health: Preventing or living with aids.

This article provides a succinct overview of the history and current and future research priorities of the Office on AIDS at the National Institute of Mental Health (NIMH). Throughout its history and currently, the Office on AIDS has encouraged and supported research on primary prevention of human immunodeficiency virus (HIV) transmission, effects of HIV disease on the central nervous system, and coping with the sequelae of infection. Future directions for the NIMH include the dissemination of research fmdings to the community, investigation of mechanisms for involving and retaining participants in large-scale vaccine trials, and continued attention to the prevention of HIV transmission through behavior change.

Tumour-specific inhibition of lymphoma growth by an antisense oligodeoxynucleotide.

In a high proportion of Burkitt lymphomas, transcription of the c-myc gene is initiated from a cryptic promoter in the first intron, creating abnormal messenger RNA molecules in which intron sequences, normally spliced out of the nascent transcripts, persist. An antisense oligodeoxynucleotide directed against these intron sequences greatly inhibited the proliferation of Burkitt lymphoma cell lines containing the abnormal transcripts (ST486 and JD38), but not that of cell lines containing normal c-myc transcripts (KK124). Flow cytometry showed a pronounced reduction in intracellular c-myc protein levels in cell lines containing aberrant myc transcripts, but no change in other cellular proteins. Control oligonucleotide did not inhibit c-myc protein expression or growth. These experiments provide evidence that antisense oligonucleotides targeted against tumour-specific, aberrant RNA species could be effective in controlling the proliferation of tumour cells without affecting normal cells.