[Malignant neoplasms and AIDS. Review of the literature and critical considerations on a case of epidermoid carcinoma of the anus]. / Neoplasie maligne e AIDS. Rassegna della letteratura e considerazioni critiche su un caso di carcinoma epidermoide dell'ano.

During the past few years the neoplasms defining the diagnosis of AIDS are in apparent evolution and a new distribution of specific tumors is currently reported in the literature. Besides the Kaposi's sarcoma, non-Hodgkin's lymphomas, and uterine cervical carcinoma, other malignancies are frequently diagnosed in HIV+ population, particularly during the advanced stages of the infection. The pathogenesis of such an increase of tumor diffusion is apparently related to the persistence of several herpes viruses including HHV8 and HPV whose molecular interaction with HIV may contribute to the genetic variations suitable for tumor development. The epidermoid anal carcinoma is a tumor whose appearance is increasingly recurrent in HIV+ patients, although it is not considered as an AIDS-defining neoplasia. This tumor is prevalent in HIV+ homosexual men, in particular during the full-blown immunodeficiency disease. Here we report the case of a patient whose diagnosis of AIDS was emphasized by the concurrent presence of the anal tumor.

[Methods for assessing programmed cell death]. / Metodiche di valutazione della morte cellulare programmata.

Apoptosis, namely programmed cell death, is a fundamental mechanism involved in both organogenesis and tissue homeostasis. Since this process is genetically controlled, its defective regulation plays a role in the pathogenesis of several diseases including inflammatory and degenerative disorders, autoimmunity and neoplasia. Several methods have been suggested to identify the cellular events including the modification of cell size, cytoplasmic condensation and nuclear degradation occurring during this phenomenon. The cell morphologic changes can be observed in detail by electronic microscopy, while the chromatin cleavage is well detected by both electrophoretic and flow cytometry techniques, using various fluorochromes able to bind specifically the double-stranded DNA. Here we review the different techniques to evaluate apoptosis with respect to their sensitivity in both qualitative and quantitative analyses.

Antiphosphatidylserine antibodies in human immunodeficiency virus-1 patients with evidence of T-cell apoptosis and mediate antibody-dependent cellular cytotoxicity.

Serum reactivities to a panel of phospholipid antigens, including cardiolipin (CL), phosphatidylserine (PS), sphingomyelin, phosphatidylcholine, and phosphatidylethanolamine, were measured by enzyme-linked immunosorbent assay in 196 human immunodeficiency virus-l+ (HIV-1+) patients with CDC II to IVC clinical disease. Significant levels of IgG to CL, PS, or both were observed in 23 patients lacking evidence of thrombophilic events or any peculiar clinical feature of HIV-1 infection. Fluorescence-activated cell sorting analyses showed that in vitro apoptosis of T cells was increased in patients with high serum anti-PS IgG, whereas the overexpression of Fas/Apo-1 marker was detected in all patients regardless of their antiphospholipid reactivities. Macrophages from patients with significant titers of anti-PS IgG antibodies were not activated by the presence of apoptotic CEM lymphoblasts or by purified anti-PS IgG from the same patients. By contrast, these antibodies greatly improved the effector functions of autologous macrophages in antibody-dependent cellular cytotoxicity (ADCC) assays using 51Cr-labeled CEM cells, whereas polyspecific IgG were unable to induce an equivalent cytotoxicity in all instances. An increasing effect on ADCC was also observed in tests using macrophages from healthy controls to CEM coated with anti-PS IgG. These results support a potential correlation of anti-PS specificity with T-cell apoptosis in HIV-1 infection. Because PS is exteriorized by apoptotic lymphocytes, its persistence may stimulate antibodies which cooperate with macrophages in the clearance of dead cells by an enhanced ADCC mechanism. This interpretation could explain the absence of thrombophilia in HIV-1+ patients with serum elevations of antiphospholipid reactivities.

Distribution and antigenic analysis of circulating F(ab')2-reactive IgG in patients with HIV-1 infection.

Serum titers and molecular specificity of anti-F(ab')2 antibodies were investigated in human immunodeficiency virus type 1 (HIV-1) infection with respect to their supposed cytopenic role on CD4+ cells. The levels of antibodies to F(ab')2 fragment and to HIV-1 glycoprotein epitopes were measured by immunoenzymatic methods in an HIV-1+ population, including 86 drug addicts, 12 sexually infected patients, and 1 hemophiliac, grouped into Walter Reed (WR) clinical stages 2 to 6 of HIV-1 infection. Monoclonal F(ab')2-reactive IgM and IgG from cloned Epstein-Barr B cell transformants of selected patients were also investigated in regards to their HIV-1 glycoprotein specificities and cytotoxicity to the CD4+ cell membrane antigens (CEM) lymphoblasts by a Terasaki assay. Group A (51 sera from WR2 patients) showed the highest titers of IgG anti-F(ab')2 with no correlation to positivities to gp120, whereas sera with undetectable anti-F(ab')2 levels from group B (37 WR5 and WR6 patients) and from group C (11 WR3-WR6 patients with lymphocytotoxin-associated lymphopenia) were reactive to the virus envelope. Both anti-F(ab')2 monoclonal IgM and IgG failed to cross-react with the HIV-1 glycoproteins and the CD4+ CEM. Based on our data, anti-F(ab')2 antibodies are apparently unrelated to the CD4+ lymphopenia occurring in HIV-1-infection. In addition, their inability to bind the HIV-1 gp120 as sequence homologue of the CH1 domain of IgG suggests that their molecular target could include a few epitopes located within the VH and VL regions, thus supporting their potential role of antiidiotype molecules as described in autoimmunity.