Effects of zidovudine in 30 patients with mild to end-stage AIDS dementia complex.

OBJECTIVE: Zidovudine (ZDV) is an inhibitor of HIV replication that may have a beneficial effect on patients with AIDS dementia complex (ADC). However, little is known about the association between long-term ZDV treatment and severity of ADC, ZDV dose or clinical and laboratory response to therapy. DESIGN: An open study on ZDV administration in 30 consecutive patients with ADC. SETTING: An infectious diseases hospital. PATIENTS: Thirty consecutive patients followed-up for 12 months. INTERVENTIONS: Three oral ZDV doses were used: 1000 mg (nine patients), 750 mg (eight patients) and 500 mg (13 patients) per day, depending on haematological status. MAIN OUTCOME MEASURES: Clinical and neurological examinations, neuropsychological evaluations, high-field brain magnetic resonance imaging (MRI) and 99mTc-HM-PAO single photon emission computerized tomography (SPECT). RESULTS: A favourable clinical response, defined as reversal to a less severe ADC stage (Price and Brew's criteria), was observed after 1, 3, 6, 9 and 12 months in 15, 22, 25, 19 and 14 patients, respectively. Neither severity of ADC at entry nor ZDV dose correlated with response to treatment. Seven patients died during the 12-month follow-up. The only factor associated with longer survival was ADC severity at entry (12-month survival, 0.94 and 0.53, in patients in stages 1 or 2 and in stages 3 or 4, respectively; P < 0.01). After 6-12 months of ZDV treatment six patients who initially responded to therapy showed a relapse in initial ADC stage, and two patients a less severe neurological deterioration. Neuropsychological evaluations showed significant improvement in the Wisconsin Card-Sorting test (P = 0.006 for categories, P = 0.029 for perseverative errors), which is particularly sensitive to cognitive and frontal-lobe type functions. Brain MRI revealed a reduction of the extent of white matter lesions in six out of 13 patients, who also showed clinical improvement. SPECT scanning revealed a reduction in the extent of uptake defects concomitant with clinical response in nine out of 14 patients. CONCLUSIONS: ZDV is effective in most patients with mild to end-stage ADC, although the benefit is sometimes only transient; several relapses and deaths occurred after the sixth month of treatment.

Identification of a CD21 receptor-deficient, non-Ig-secreting peripheral B lymphocyte subset in HIV-seropositive drug abusers.

We have studied 61 HIV-seropositive heroin addicts (18 asymptomatic, 20 ARC, and 23 AIDS cases), 26 HIV-seronegative heroin addicts, and 45 healthy blood donors, matching the groups each other for age and sex. We have focused on the phenotypic characteristics of B subpopulations in the peripheral blood of HIV-seropositive and -seronegative drug abusers, paying particular attention to the consistence of the "CD20+" B cell subset, which poorly expresses the CD21 membrane receptor for the C3d and Epstein-Barr virus (EBV) (referred to as "CD20 + CD21-" subset). In healthy blood donors, the ratio CD20 + CD21-/CD20+ x 100 is extremely low (mean +/- SEM = 8.1 +/- 0.9) and rarely exceeds the value of 20. On the contrary, in HIV seropositives, the values are much more dispersed, with higher mean values (mean +/- SEM = 25.8 +/- 1.8) ranging from 50 to 60. An intermediate situation characterizes the class of HIV-seronegative heroin addicts, whose values are slightly higher and more dispersed than that of normal controls (mean +/- SEM = 11.6 +/- 1.3). The extent of the amplification of the CD20 + CD21- subset in HIV-seropositive individuals does not apparently correlate with the progression of the disease and represents an early event in the clinical course of HIV infection. For each subject of the study group, the number of CD20 + CD21- B lymphocytes is not correlated to other early markers of HIV infection, as the T4 lymphocyte number, or total Ig levels in sera. A functional characterization of the CD20 + CD21- B cell subset indicates that, in HIV-seropositive patients, these cells are unable to produce specific and nonspecific immunoglobulins (Ig's), either spontaneously or after pokeweed mitogen stimulation. Furthermore, this cell subset is characterized by poor expression of surface Ig's. The data reported suggest that this cell subset can be regarded as situated at an early level of B cell lineage differentiation.

Sendai virus replication in Friend erythroleukemia cells. I. Acutely and persistently infected cells become resistant to virus-induced lysis.

Friend leukemia cells (FLC) are susceptible to infection by Sendai virus, a member of the paramyxovirus group. FLC constitute a most suitable model to study virus-host cell interactions, because they grow in suspension (thus avoiding the use of trypsin), and provide an easy way of deriving single-cell clones. When FLC are infected with Sendai virus at high m.o.i., a direct, extensive lysis of the cells ensues, whereas lower doses of virus result in a cytocidal infection whose lethality depends mainly on the virus used, standard or defective interfering egg-grown Sendai virus (EGSV), and on the multiplicity of infection (m.o.i). At later times after infection, FLC become resistant to the Sendai induced lysis (SIL). The SIL resistance can be maintained in single-cell clones that had survived the first infection. The maintenance of the resistant phenotype of the clones requires the serial subcultivation of the cells in the presence of activated EGSV. The mechanisms that presumably regulate the appearance of SIL resistance in Sendai infected FLC are discussed.

A nonneutralizing human IgM monoclonal antibody inhibiting hemagglutination of H3N2 influenza A strains.

A mouse-human hybridoma has been produced by fusing human splenocytes from a Cooley's anemia patient with the murine myeloma P3-NS1/1-Ag 4-1. The hybridoma is stable after 18 months and secretes human IgM. The antibody reacts with some H3N2 influenza A strains and detects an epitope that is part of the hemagglutinin antigen, but does not affect virus infectivity.