[Anterior orbital ischemia secondary to type 1 cryoglobulinemia: A case report and literature review]. / Ischémie du segment antérieur de l'œil secondaire à une cryoglobulinémie de type 1 : à propos d'un cas et revue de la littérature.

INTRODUCTION: Type 1 cryoglobulinemia is characterized by a large number of clinical signs. The lack of specificity of these signs can make diagnosis difficult. Ocular manifestations are rarely described across medical literature. Only 15 cases of ophthalmological involvement secondary to cryoglobulinaemia have been reported. COMMENT: We report the case of a 69-year-old patient with cutaneous type 1 cryoglobulinaemia. He presented with bilateral anterior segment ischemia without retinal involvement with unilateral neovascularisation. Treatment of the B lymphocyte clone with rituximab and bendamustine and plasma exchange were initiated with successfully. Two similar cases describing ischaemic damage to the iris during type 1 cryoglobulinemia have been reported in the literature. CONCLUSION: Irial ischaemia should be considered as a potential in type 1 cryoglobulinaemia.

Repair of the in vitro HIV-1-induced immunosuppression and blockade of the generation of functional suppressive CD8 cells by anti-alpha interferon and anti-Tat antibodies.

The acute human immunodeficiency virus type 1 (HIV-1) infection of activated peripheral blood mononuclear cells (PBMCs) from normal donors results in inhibition of cell proliferation and generation of functional suppressive T cells. Cultured HIV-1 infected PBMCs but not uninfected PBMCs, following irradiation, can inhibit the proliferation of antigen-activated autologous T cells in a dose-dependent way. CD8+ cell subpopulation is responsible for this inhibition. The presence of anti-alpha interferon (IFN alpha) and anti-Tat antibodies in the culture medium counteracts the HIV-1-induced immunosuppression and prevents the generation of suppressive T cells by these PBMCs. The reported data should have major implications for strategies of AIDS treatment which, in association with antiviral drugs, aim at targetting immune disorders.

Which nutrient supplements for optimal HIV-1 production by cultured human lymphocytes?

Under standard conditions, all established cell-lines of HIV-1-infected lymphocytes are cultured in a medium containing a high percentage of serum. We have found that whilst partial or total serum depletion impedes their cell growth, it dramatically increases their virus production. Serial subcultures in serum-depleted medium are necessary to insure permanent cell growth and a relatively high reverse transcriptase activity. Following optimization of culture conditions, both HIV-infected and uninfected H9 cells have been regularly grown in a new protein-free medium. Such chemically defined culture conditions were required to detect the effect of minor components, such as vitamins, on host cell-virus interactions.

Evidence for an antiviral effect and interferon neutralizing capacity in human sera; variability and implications for HIV infection.

The antiviral effect (AVE) and interferon neutralizing capacity (INC) of sera originating from either seronegative or HIV-infected individuals were determined. As a rule, sera from seropositive subjects exhibited higher AVE titers than sera from seronegative individuals. Similarly, the INC of sera from HIV-infected patients, was most often stronger than that of sera from seronegative individuals. Furthermore, sera from HIV-infected patients actively immunized with i-IFN alpha invariably expressed INC in response to treatment, which was not the case for sera from control unimmunized patients. All sera from HIV-infected patients were found by ELISA to contain antibodies specifically directed to IFN alpha.

Biological effect of active anti-IFN alpha immunization in HIV-infected patients.

Circulating interferon (IFN) was investigated in HIV-1 seropositive patients by measuring the IFN alpha antiviral effect in the serum. While serum of healthy seronegative individuals exhibits an antiviral effect, not due to IFNs, considered as background, serum of seropositive patients showed an additional antiviral effect due to the abnormal presence of IFN alpha. Increased titers of IFN alpha were found in the course of the HIV infection and seemed to correlate with the evolution of AIDS disease. Furthermore, patients immunized against IFN alpha had both stabilized CD4 cell count and decreased IFN alpha in their serum. HIV-1-infected patients also exhibited higher titers of natural anti-IFN antibodies than seronegative controls and the level of specific antibodies (Abs) markedly increased in immunized patients. Finally, serum from immunized patients, when compared to seronegative controls, exhibits an interferon neutralizing capacity.

Antioxidant system in rat testicular cells.

The activity of the enzymes involved in the antioxidant defence--superoxide dismutase (SOD), glutathione peroxidase (GPx), reductase (GR), S-transferase (GST)--as well as the glutathione (GSH) levels were measured in different rat testicular cell populations. A differential distribution of these components among testicular cell types was clearly observed. Sertoli and peritubular cells had elevated SOD and GSH-dependent enzyme activities associated with a high GSH content. Compared with the somatic cells, pachytene spermatocytes (PS) and round spermatids (RS) presented a different antioxidant system characterized by higher SOD activity and GSH content associated with very low GSH-dependent enzyme activity. Spermatozoa exhibited the same enzymatic system as PS and RS but were devoid of GSH. Interstitial tissue displayed high GSH content, moderate SOD and GSH-related enzyme activity except for GPx which was very elevated. It is concluded that the different categories of testicular cells probably display a highly variable susceptibility to oxidative stress.

Effect of purified IgGs from HIV-1-infected and non infected individuals on immune activation.

The purification and analysis of IgGs from sera of HIV-1-infected and non infected individuals are reported. The effect of antibodies purified from sera of infected individuals on antigen-induced T cell proliferation was investigated in relation to their possible involvement in an autoimmune reaction in AIDS, in view of the previously unravelled striking peptide similarities between HIV-1 gp120 and the immunoregulatory CD4 and Fas molecules. However, our data do not allow definite conclusions to be drawn. The necessity of purifying antibodies against specific peptides to show their direct effect on T-cell activation is further stressed.

Lisinopril versus atenolol: decrease in systolic versus diastolic blood pressure with converting enzyme inhibition.

In a multicenter, parallel, double-blind study, lisinopril, a new converting enzyme inhibitor, was compared with atenolol in the treatment of mild to moderate essential hypertension. Four hundred ninety patients were randomized to once-a-day treatment with lisinopril 20 mg or atenolol 50 mg for 4 weeks, and the doses of lisinopril or atenolol were increased at 4-week intervals up to 80 mg or 200 mg, respectively, if sitting diastolic blood pressure (SDBP) was not well controlled. Lisinopril and atenolol reduced SDBP to a similar extent. All reductions from baseline in sitting diastolic and systolic blood pressure were significant (p less than 0.01). Lisinopril produced a significantly greater reduction (p less than 0.01) in sitting systolic blood pressure (SSBP) than atenolol. The predominant reduction in SSBP could not be explained on the basis of age, race, or severity of hypertension. It is suggested that the increase in arterial compliance reported for converting enzyme inhibitors could explain the predominant decrease in systolic blood pressure.

Discriminating between protective and enhancing HIV antibodies.

Most attempts to produce a vaccine against HIV-1 infection are utilizing envelope protein components. Hypothetically such vaccine candidates could stimulate production of antibodies that enhance HIV-1 infection via the macrophage route of entry and, consequently, cannot be detected in the conventional neutralization assay. To study this hypothesis we report an assay designed to evaluate the protective/enhancing activity of serum from seropositive immunized or infected individuals. Highly purified activated FcR-bearing monocytes-macrophages were infected with HIV-1 in the presence of the sera, then washed and cocultured with activated peripheral blood mononuclear cells (PBMC) from a normal donor. Productive viral infection, as evaluated by p24 antigen semiquantitative assay in the culture supernatants, allow evaluation of protective/enhancing activity of the sera. The data clearly show that protective rather than enhancing activity is present in the serum of env protein-immunized individuals.

Persistent HIV-2 infection of rhesus macaque, baboon, and mangabeys.

Six monkeys of three different species (mangabey, macaque and baboon) were infected with human immunodeficiency type 2 (HIV-2) NIH-DZ using intraperitoneal or intravenous injections of cell-free HIV-2 or autologous HIV-2-infected cells with no prior immunostimulation. Viral expression was demonstrated by reverse transcriptase activity in cells after coculture with human peripheral blood lymphocytes or by electron microscopy. Serum was analyzed by western blot, enzyme-linked immunosorbent assay (detection of antigen and antibody), and neutralization assay carried out using immunofluorescence techniques. The 6 inoculated animals seroconverted during the 1st month after inoculation and remained persistently infected after 6-11 months. We also observed proviral DNA by genomic analysis in the six tested samples. No sign of immunodeficiency disease has been observed so far. The data suggest that HIV-2 infection of nonhuman primates provides an acceptable animal model to investigate vaccination or specific immunotherapeutic procedures.

Even transcriptionally competent proviruses are silent in bovine leukemia virus-induced sheep tumor cells.

To investigate the role of proviral integration and expression in cellular transformation induced by bovine leukemia virus (BLV), three BLV-induced tumors harboring a single proviral copy were selected upon restriction and hybridization analysis. Tumors 344 and 395 were shown to contain a full-size proviral copy, whereas in tumor 1345 the provirus appeared to be heavily deleted. RNA gel blot hybridization with an antisense RNA probe showed no transcription of the viral sequences in the fresh tumors or in sheep tumor cells growing in vitro. The proviruses were cloned and transfected in mammalian cell lines. Transient-expression experiments revealed that the complete proviruses were still able to express the trans-activating protein (Tat) as well as structural proteins, demonstrating that the nonexpression of a provirus in a tumor cell does not necessarily imply a structural alteration of the viral information. In contrast, sequence analysis of the provirus with a large deletion and transient-expression assays proved that this truncated provirus, isolated from a tumor, was unable to code for viral proteins. These data indicate that expression of viral genes, including tat, is not required for the maintenance of the transformed state.

Inflammatory lesions of peripheral nerve in a patient with human T-lymphotropic virus type I--associated myelopathy.

In a patient with tropical spastic paraparesis associated with a positive titer for human T-lymphotropic virus type I, electrophysiological study detected a mixed, axonal and demyelinating, multifocal neuropathy. Perineural and perivascular infiltrates, moderate axon loss, wallerian degeneration, and demyelinating lesions of isolated fibers were present in the nerve biopsy specimen. These inflammatory lesions resembled those found in the central nervous system of patients with tropical spastic paraparesis.

A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS.

The first experimental immunization of humans against the AIDS retrovirus, HIV-1, was started in a series of HIV seronegative, healthy volunteers in November 1986. For the primary vaccination recombinant vaccinia virus (V25) expressing the complete gp160 env protein of the HTLV-IIIB strain of HIV-1 was introduced by scarification. This elicited a weak primary response which we subsequently attempted to enhance by additional immunizations (boosting), using four different immunization protocols. We report here that intravenous injection of paraformaldehyde-fixed autologous cells infected in vitro with V25 (individual D.Z.) gave the best results. This individual received second and third boosts of intramuscular gp160 derived from an HTLV-IIIB clone using the hybrid vaccinia virus/bacteriophage T7 expression system. An anamnestic humoral and cellular immune reaction was achieved for over one year after the original vaccination, with high levels of antibodies to the viral envelope, and neutralizing antibodies against divergent HIV-1 strains such as HTLV-IIIB and HTLV-IIIRF (also called HTLV-III HAT) after the first boost. In addition, group-specific cell-mediated immunity and cell-mediated cytotoxicity against infected T4 cells were obtained after the primary vaccine and enhanced by the boosts. Finally, skin tests showed both immediate and delayed hypersensitivity to gp160 in vivo. Although this protocol is not practical for a large scale vaccine trial, our results show for the first time that an immune state against HIV can be obtained in man.

Rationale for ACE inhibition in the elderly: treatment of arterial hypertension with enalapril.

A randomized, double-blind, placebo-controlled trial was conducted with 32 elderly patients (aged 75-97 years) with uncomplicated essential hypertension, to evaluate the efficacy and tolerance of enalapril, an angiotensin-converting enzyme inhibitor. It was given over an 8-week period in doses from 20 to 40 mg/day and was compared with an identical placebo. Enalapril caused a significant reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by the 2nd week, an effect that persisted through to the 8th week (190 +/- 16/102 +/- 7 to 151 +/- 19/85 +/- 11 mm Hg); 67% of patients had their pressures normalized (less than 160/95 mm Hg). BP was also significantly decreased by the 8th week under placebo (183 +/- 16/101 +/- 9 to 165 +/-21/91 +/- 13 mm Hg), but only 35% of patients attained a normal pressure. Heart rate did not change with treatment. Enalapril caused an increase in plasma renin activity (1.22 +/- 0.08 to 3.66 +/- 2.50 ng/ml/h), whereas aldosterone levels remained unchanged. There was a mild, significant elevation of creatinine level with enalapril but other laboratory parameters, including serum potassium, were unaltered. Two deaths occurred in the enalapril group, but were not considered to be treatment-related. The drug was otherwise well tolerated. Serum enalapril concentration was assessed in 10 patients taking 20 mg/day over an 8-day period. At equilibrium, the level was 22.3 +/- 5.0 ng/l and it correlated both with converting enzyme inhibition and with renal function. Enalapril is shown to be an effective and well-tolerated antihypertensive medication in elderly patients.

Evidence for HTLV-III/LAV expression by primary cultures of T8 cells.

The selective targets for HTLV-III/LAV, the causal infectious agent of AIDS and AIDS-related complex (ARC), are T4 cells, apparently because the virus receptor is associated with T4 antigen determinants. This accounts for T4 cell depletion in AIDS and for a decrease of IL-2 production by AIDS peripheral blood lymphocytes (PBL) after in vitro PHA activation. By contrast, T8 cells are not targets for HTLV-III/LAV, since T8 cells from PBL and from long-term cultured T cells (CTC) could not be infected by the virus. We describe 2 samples of PBL from Zairian patients with HTLV-III infection in which HTLV-III was expressed by T8 cells. Evidence that T8 cells were expressing virus was obtained by complement cytotoxicity experiments performed in the presence of OKT8 monoclonal antibody (MAb), which removed HTLV-III-positive cells from cultured T cells producing the virus, and by double labelling experiments, in which some cells exhibit both T8 antigens detected either by IFA (rhodamine) or by rosetting in presence of OKT8 MAbs and HTLV-III antigens detected by IFA (fluorescein) with of anti-HTLV-III p24 and p15 MAbs. Since normal T cells have previously been shown to undergo antigenic diversity, we think these results can be explained by HTLV-III infection of T4 cells which later lost T4 antigens and acquired the T8 phenotype.