[Role of TH1 and TH2 in the pathogenesis of AIDS and various other diseases].
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
Z Bentwich
Publications and source records attributed to Z Bentwich.
Urinary organ specific neoantigen. A potentially diagnostic test for colorectal cancer.
Urinary organ-specific neoantigen from colorectal cancer patients has been used to make a monoclonal antibody, BAC 18.1. In this study we assessed the potential of this antibody for the diagnosis of colorectal cancer. We evaluated binding in both urine and effluent samples and compared it with effluent carcinoembryonic antigen standardized for both volume (nanograms per milliliter) and protein. Urinary organ-specific antigen as detected by BAC 18.1 was significantly greater in 29 cancer patients (A405: 0.717 +/- 0.500) vs 27 controls [0.121 +/- 0.273 (P < 0.05)]. Considerable overlap of binding of BAC 18.1 was observed in the colonic effluent of patients with CRC (N = 13), adenomas (N = 26), inflammatory bowel disease (N = 8), or having a normal colonoscopic examination (N = 24). CEA levels (nanograms per milliliter) were significantly elevated in the effluent samples of patients with a past history of colorectal cancer, as compared to that of normal individuals (P < 0.05). The presence of the M(r) 30,000 organ-specific neoantigen in colonic effluent was also demonstrated by western blot. Organ-specific neoantigen originates in the colon and is excreted into the urine, so the BAC 18.1 binding levels in the urine may be a diagnostic aid for CRC.
Adult↗
Immune activation is a dominant factor in the pathogenesis of African AIDS.
The AIDS epidemic in Africa is very different from the epidemic in the West. As suggested here by Zvi Bentwich, Alexander Kalinkovich and Ziva Weisman, this appears to be primarily a consequence of the over-activation of the immune system in the African population, owing to the extremely high prevalence of infections, particularly helminthic, in Africa. Such activation shifts the cytokine balance towards a T helper 0/2 (Th0/2)-type response, which makes the host more susceptible to infection with human immunodeficiency virus (HIV) and less able to cope with it.
Acquired Immunodeficiency Syndrome↗
Increased soluble tumor necrosis factor receptor expression and release by human immunodeficiency virus type 1 infection.
High levels of circulating soluble tumor necrosis factor receptors (sTNF-R) are associated with HIV-1 infection and disease. To understand better this association, we have investigated p55 and p75 TNF-R expression on peripheral blood mononuclear cell (PBMC) subsets and in the promonocytic cell line U937, with or without HIV infection. Using flow cytometry and monoclonal antibodies both to sTNF-R and to PBMC subsets, TNF-R were found to be expressed mostly by monocytes and in decreasing amounts and intensity in the following order: CD14+ cells > CD8+ cells > CD4+ cells. Expression of TNF-R was higher on cells obtained from HIV-infected than from noninfected subjects, and expression of p75 sTNF-R was much higher than that of p55 sTNF-R. Studying the U937 cells revealed that over 80% of the cells expressed both sTNF-R, but with greater fluorescence intensity in the HIV-1 chronically infected cells (U-937-IIIB). Treatment of the cells with PMA caused an accelerated release into the medium of both sTNF-R, with a sharp decline in their cell surface expression. Basal levels of mRNA transcripts for p75 TNF-R were higher in the U-937-IIIB cells than in the uninfected cells, but p55 TNF-R mRNA was expressed only in the HIV-1-infected cells. These findings show that HIV-1 infection is accompanied by predominant elevation of p75 TNF-R surface expression on monocytes and CD8+ lymphocytes, and results in both increased message and expression of these receptors in monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Acquired Immunodeficiency Syndrome↗
Pending problem of "silent" human immunodeficiency virus infection.
The problem of "silent" HIV infection is reviewed. Overall, the number of proven "silent" infection in several at-risk populations, including HIV exposed health-care workers, homosexuals, IV drug addicts and children born to HIV-infected mothers, has been very low. Contrary to these observations, we describe a very high prevalence of HIV specific immunity and positive HIV specific PCR signals in an Ethiopian immigrant population recently arrived in Israel. The interpretation of these findings is not entirely clear but we suggest that host immunity and probably different handling of the infection may account for the longer persistence of viral components in the body. Further studies are required to determine the amount and nature of these viral elements and, most importantly, whether they are still infectious.
Acquired Immunodeficiency Syndrome↗
Immune activation, a co-factor for HIV transmission in Thailand?
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Acquired Immunodeficiency Syndrome↗
Chlamydia trachomatis and HIV infection.
To study the interactions between Chlamydia trachomatis (CT) and human immunodeficiency virus (HIV) infections, we examined CT serologies in sequential serum samples of male homosexuals (MHS), followed over a mean period of 4 years. Of the MHS studied, 77 were HIV(-), 18 were HIV(+) and 10 patients seroconverted during the study period. Seventy matched heterosexual controls were tested concomitantly. CT-specific antibodies of both IgG and IgA isotypes were determined by an immunoperoxidase assay, indicating past and active infection respectively. Anti-CT IgG was frequently observed in both HIV(-) and HIV(+) MHS (40-50% vs. 23% of controls) and IgA antibodies were also common in both MHS groups (15-20% vs. 1.5% of controls). After HIV infection, no increase in CT antibodies occurred. We found serological data suggestive of active CT infection preceding seroconversion in 3 of 10 seroconverters vs. 5% of matched MHS controls who remained HIV(-) (P < 0.025), indicating a possible effect of CT infection on the acquisition of HIV should be further studied.
AIDS-Related Opportunistic Infections↗
A sex comparison of rates of new AIDS-defining disease and death in 2554 AIDS cases. AIDS in Europe Study Group.
OBJECTIVES: To compare the development rate of new AIDS-defining diseases between 566 women and 1988 men with AIDS who were infected with HIV via the same routes (mainly by sharing drug injecting equipment and heterosexual sex). DESIGN: Information on patient follow-up after AIDS diagnosis was obtained by retrospectively reviewing case notes. METHODS: The 2554 men and women were followed from the time of AIDS diagnosis as part of the multicentre AIDS in Europe study, which examined AIDS cases diagnosed at 52 centres in 17 European countries between 1979 and 1989. Incidence of AIDS-defining diseases and demographic variables were recorded for all patients and CD4 lymphocyte count at the time of AIDS diagnosis for approximately half the patients. RESULTS: Only toxoplasmosis and herpes simplex virus ulceration showed statistically significant differences in occurrence rate between women and men [relative risks (RR), 1.51 and 3.44; 95% confidence interval (CI), 1.51 1.09-2.08 and 3.44 1.92-6.23, respectively] which remained after adjusting for imbalances in other variables. For both diseases, the additional absolute rate in women was approximately three per 100 person-years at risk. Survival after AIDS diagnosis was also similar between the two sexes (RR, 0.96; 95% CI, 0.86-1.08). CONCLUSION: There appears to be little difference between women and men in the clinical course of AIDS.
AIDS-Related Opportunistic Infections↗
Increased p43-isoferritin in Ethiopian immigrants in Israel--a marker for immune activation.
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Biomarkers↗
The beneficial effect of the estrogen antagonist, tamoxifen, on experimental systemic lupus erythematosus.
OBJECTIVE: To determine the effects of the estrogen antagonist, tamoxifen, on the development and the course of experimental murine systemic lupus erythematosus (SLE). METHODS: SLE was induced in naive BALB/c female mice by injection of the human monoclonal anti-DNA antibody bearing the 16/6 idiotype (Id). Six weeks following immunization, when high levels of autoantibodies were demonstrated, the mice were treated with tamoxifen (200-800 micrograms/mouse twice a week) up to a period of 8 months. In several mouse groups tamoxifen treatment was started as late as one year following the immunization with the 16/6 Id when overt disease was already observed. RESULTS: Tamoxifen treatment had no effect on the 16/6 Id induced autoantibody production. However, the 16/6 Id immunized and tamoxifen treated mice demonstrated normal numbers of white blood cells (WBC) and thrombocytes while the untreated groups had significant leukopenia and thrombocytopenia. Similarly, persistent proteinuria and immune complex deposits in the kidneys were observed in the 16/6 Id immunized mice whereas no such deposits were found in kidney sections of 16/6 Id immunized mice that were treated with tamoxifen. Delayed tamoxifen treatment (starting a year following the immunization) also demonstrated beneficial therapeutic effects. CONCLUSION: These studies demonstrate therapeutic effects of tamoxifen on murine experimental SLE suggesting a possible role for this estrogen antagonist in the treatment of human SLE and related disorders.
Animals↗
[Nutrition and HIV infection].
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Acquired Immunodeficiency Syndrome↗
From HIV infection to AIDS: are the manifestations of effective immune resistance misinterpreted?
Viewing the immune system as part of an adaptive communication network, rather than merely a coalition of effectors, we argue that the alterations in the immune system that occur in HIV-infected patients, generally considered to be "abnormalities," cannot be attributed directly to deleterious effects of the virus on CD4+ T cells or other particular cells. Rather, many of the functional changes that occur during the asymptomatic phase reflect a normal mode of immune resistance to chronic infection, different from the "stereotypic" immune response, whereby patterns of signals are recognized and classified and evoke selective activities. The relative stability of the virus-host relationship in this phase involves a degree of mutual adaptation. However, an excessively perturbed microenvironment is the core of unstable cellular organization in which the resistance to infection gradually deteriorates. We suggest that this is due to "overadaptation" of lymphocytes and accessory cells to the infectious agent(s). We further speculate that a key factor underlying this process is a reduced rate of replacement of CD4+ T cells, which are sequestered at the sites of infection, by fresh unprimed or memory T cells. Direct and local viral effects are amplified and propagated by "affected" cells, which are not necessarily infected. The collective profile of gene expression in various types of affected cells might adequately reflect tissue organization and the overall functional status of the immune system and thus could serve as a guide to therapy. This would require collection of a more extensive array of immunologic data than is now gathered, and novel approaches to analyzing such data.
Acquired Immunodeficiency Syndrome↗
The leukocyte adherence inhibition test (LAI) in preoperative diagnosis of epithelial ovarian cancer.
One hundred two women admitted for evaluation of an adnexal mass were tested prior to surgery by the computerized tube leukocyte adherence inhibition (LAI) assay. The test was positive in 24/35 (69%) patients, diagnosed after surgery as epithelial ovarian cancer while 50/67 (75%) of those diagnosed as benign masses were negative. Only 2/38 (5%) of normal control subjects showed a false-positive result. The LAI test described in this report showed a sensitivity of 88% and a specificity of 75% in stage I ovarian cancer; thus it may be useful for early diagnosis of ovarian malignancy.
Adnexal Diseases↗
Monoclonal anticardiolipin antibodies derived from mice with experimental lupus erythematosus: characterization and the induction of a secondary antiphospholipid syndrome.
The primary antiphospholipid syndrome and the antiphospholipid syndrome in systemic lupus erythematosus (SLE) patients (defined as secondary antiphospholipid syndrome) are characterized by the presence of anticardiolipin antibodies, thrombosis, thrombocytopenia, and recurrent fetal loss. To determine the role of anticardiolipin antibodies in the pathogenesis of antiphospholipid syndrome, monoclonal anticardiolipin antibodies were derived from mice in which experimental lupus was induced by a murine monoclonal anti-16/6 Id antibody. Two murine monoclonal anticardiolipin antibodies (2C4C2, 2C4D1) were generated and characterized. The 2C4C2, but not the 2C4D1, monoclonal antibody demonstrated remarkable lupus anticoagulant activity. Furthermore, these murine anticardiolipin monoclonal antibodies appear to recognize antigenic epitopes similar to those recognized by anticardiolipin antibodies found in sera of SLE patients. The monoclonal anticardiolipin antibody 2C4C2 was injected into naive female mice. Following immunization, the mice developed high titers of autoantibodies reacting with cardiolipin, DNA, nuclear extract, 16/6 and anti-16/6 Id, and anticardiolipin antibodies. As early as 8 weeks after immunization these mice exhibited significant leukopenia, thrombocytopenia, and proteinuria with immune complex glomerulonephritis. Moreover, mating of 2C4C2-injected mice with allogenic males resulted in low pregnancy rates and a low number of fetuses with a high percentage of fetal loss. These studies provide a new experimental model for secondary antiphospholipid syndrome demonstrating the role of anticardiolipin antibodies in the pathogenesis of this syndrome.
Animals↗
Soluble tumour necrosis factor receptors (sTNF-R) and HIV infection: correlation to CD8+ lymphocytes.
The objective of this study was to determine sTNF-R, type I (p55) and type II (p75) in sera of HIV-infected male homosexuals and correlate them to T lymphocyte subpopulations and course of HIV infection. Serum samples were obtained from 39 HIV-1+ asymptomatic male homosexuals, 10 symptomatic (ARC and AIDS) male homosexuals and 44 HIV- non-homosexual healthy controls. sTNF-R levels were determined by ELISA with specific MoAbs and polyclonal antibodies to the sTNF-R proteins. sTNF-RI and II levels were significantly elevated in 72% and 74% respectively of HIV+ asymptomatic male homosexuals and in all of the symptomatic male homosexuals. In sequential studies a highly significant positive correlation was found between sTNF-RI and sTNF-RII (r = 0.8, P < 0.001) and between both sTNF-R and CD8+ lymphocyte counts (r = 0.6 and 0.92, respectively, P < 0.01-0.001) during the asymptomatic stage of the infection. All these correlations were lost, however, during the symptomatic phase of the disease. These results suggest that: (i) HIV infection is associated with elevation of sTNF-R serum levels; (ii) sTNF-R levels are strongly correlated to CD8+ lymphocytes during the asymptomatic stage of HIV infection.
Adult↗
HIV resistance to anti-viral drugs.
The use of zidovudine (ZDV) and other forms of nucleoside therapy, including dideoxyinosine (ddI), to treat HIV-infected individuals has led to both longer survival and improved quality of life. However, ZDV-resistant variants of HIV-1 can be isolated from patients undergoing prolonged therapy with this drug. HIV drug resistance against ZDV, ddI and other nucleosides is attributable to a series of point mutations within the pol gene of HIV-1 that encodes the viral enzyme, reverse transcriptase (RT). This is not surprising, since the virus is known to replicate at high rates in infected individuals; moreover the RT which mediates transcription of proviral DNA from viral genomic RNA is known to be highly error-prone. Thus, mutants of HIV-1, which possess a drug resistance phenotype and genotype, may be expected to emerge under the selective pressure of long-term anti-viral chemotherapy. HIV drug resistance occurs most commonly in individuals with low CD4 counts, who have progressed to more serious forms of disease. Moreover, viruses obtained from patients with AIDS generally display higher levels of resistance, relative to pre-treatment isolates, than do viruses from patients with more limited illness. Although observations of drug resistance can be correlated with disease progression and a weakened immune system, it is still unclear whether a cause and effect relationship exists. Current clinical research is designed to answer this question while testing the notion that combinations of nucleosides and immuno-stimulatory drugs may provide important clinical benefits.
Cross Reactions↗
Clinical, epidemiological and natural history study of HIV-1 infection among seropositive homo/bisexuals in Israel, 1986-92. A collaborative study in three medical centers.
The clinical and epidemiological aspects of HIV-1 seropositive homo/bisexuals at three AIDS screening clinics in Israel were analyzed retrospectively for the 4-year period 1986-92. Of 1,526 individuals who attended the clinics a total of 238 (15.5%) were found to be HIV-1 seropositive; 182 seropositives were followed for a mean of 3.3 (+/- 2.6) person-years. The incidence of AIDS in this cohort was 33% over 4 years, a rate of 9.8/100 person-years. Half of all HIV-1 seropositives are estimated to have been infected outside Israel. On initial presentation 144 (62%) were asymptomatic and 94 (38%) were symptomatic. CD4 levels were > 500 ml3 in 87 (36%), 200-500 ml3 in 66 (28%) and < 200 ml3 in 45 (19%) individuals. The pattern of clinical presentations was similar to that seen in the West, but mycobacterial infections were rare. A cohort of 86 homo/bisexuals with full-blown AIDS was followed for a mean of 2.2 person-years. The mortality rate in this group was 53.5% over 4 years, a rate of 26/100 person-years. Thus, HIV infection among Israeli homosexuals ceased to be a rarity as it took the pattern of AIDS in the West, with some special features such as the late presentation of patients for medical treatment and the paucity of mycobacterial diseases complicating the disease.
AIDS-Related Opportunistic Infections↗
Host immunity and the course of HIV infection.
HIV infection and disease are determined to a large extent by the host's immune response. Exposure to the virus alone does not lead necessarily to long-lasting infection and the progress of HIV infection once established varies in different individuals. The development of host immunity, while either "protective" or "enhancing," will determine all these outcomes.
Acquired Immunodeficiency Syndrome↗