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Biomedical subjects

C Rinaldo

Publications and source records attributed to C Rinaldo.

At least 19 recordsLinked to original sources
PubMed2005

High Mobility Group A1 (HMGA1) proteins interact with p53 and inhibit its apoptotic activity.

HMGA gene overexpression and rearrangements are frequent in several tumours, but their oncogenic function is still unclear. Here we report of a physical and functional interaction between High Mobility Group A1 (HMGA1) protein and p53 oncosuppressor. We found that HMGA1 binds p53 in vitro and in vivo, and both proteins are present in the same complexes bound to the Bax gene promoter. HMGA1 interferes with the p53-mediated transcription of p53 effectors Bax and p21(waf1) while cooperates with p53 in the transcriptional activation of the p53 inhibitor mdm2. This transcriptional modulation is associated with a reduced p53-dependent apoptosis in cells expressing exogenous HMGA1 and p53, or in cells expressing endogenously the proteins and in which p53 was activated by UV-irradiation. Furthermore, antisense inhibition of HMGA1b expression dramatically increases the UV-induced p53-mediated apoptosis. These data define a new physical and functional interaction between HMGA1 and p53 that modulates transcription of p53 target genes and inhibits apoptosis.

Apoptosis↗
PubMed1992

Low prevalence of HIV in high-risk seronegative homosexual men evidenced by virus culture and polymerase chain reaction.

OBJECTIVE: To assess the presence of covert HIV-1 infection. SETTING: High-risk seronegative homosexual men from the Pittsburgh portion of the Multicenter AIDS Cohort Study were examined for the presence of HIV-1 infection. PATIENTS, PARTICIPANTS: Ten men (group 1) were examined prospectively for the presence of HIV-1 in their freshly-obtained peripheral blood mononuclear cells (PBMC). Furthermore, cryopreserved PBMC from 26 men (group 2) at their first visit (1984-1985) were examined retrospectively for the presence of HIV-1. MAIN OUTCOME MEASURES: PBMC samples from groups 1 and 2 were examined for HIV-1 by polymerase chain reaction (PCR) using gag, env and strong-stop (long terminal repeat) specific primers. In addition, fresh PBMC samples from group 1 were examined for HIV-1 by virus culture. RESULTS: None of the 10 PBMC samples from group 1 were positive for virus culture and PCR. Only one of the 26 men from group 2 was positive for gag and strong-stop DNA sequences. This PCR-positive, seronegative subject was found to be negative for HIV-1 by PCR at follow-up visits up to 48 months later. None of 15 seronegative, low-risk homosexual men and 12 seronegative heterosexual men were found to be PCR-positive for HIV-1. However, six HIV-1-seropositive men were positive by PCR for gag, env, and strong-stop HIV-1 DNA sequences. CONCLUSIONS: These results suggest a low prevalence of covert HIV-1 infection in high-risk seronegative homosexual men in our geographic area.

Adult↗
PubMed1992

Proliferation of cytomegalovirus-primed lymphocytes in bronchoalveolar lavages from lung transplant patients.

Previous reports have described an association between cytomegalovirus infection and increased donor-specific alloreactivity of bronchoalveolar lavage (BAL) lymphocytes in transplanted lungs and a higher risk of bronchiolitis obliterans due to chronic rejection. We have postulated that during infection, intragraft CMV-specific lymphocytes are activated and release lymphokines that augment cellular rejection. This study deals with an analysis of CMV antigen induced proliferation of 28 BAL lymphocyte and 27 peripheral blood lymphocytes samples from 17 lung transplant patients with or without CMV infection. Kinetic studies of lymphocyte proliferation have shown that CMV infection of the lung allograft is associated with an accelerated response of BAL lymphocytes but not PBL, following in vitro exposure to CMV antigen. These findings indicate an accumulation of primed CMV-specific lymphocytes within the lung allograft during CMV infection. Evidence has also been obtained that primed CMV-specific lymphocytes may persist for months in BAL. We conclude that the CMV antigen induced proliferation assay is useful for studies of CMV infection in transplant patients.

Antigens, Viral↗
PubMed1992

The significance of western blot assays indeterminate for antibody to HIV in a cohort of homosexual/bisexual men. The Multicenter AIDS Cohort Study.

The objective of this study was to determine the frequency and significance of nondiagnostic Western blot (WB) assays in homosexual/bisexual men at risk of infection with HIV-1. The presence of a positive enzyme-linked antibody assay (EIA) confirmed by a positive WB was used as evidence of infection and seroconversion. Indeterminate WB assays were defined as reactions to only one viral gene product of HIV-1. Three analyses were conducted to (a) determine the frequency of such reactions in men who, during a 4-year period, did not develop diagnostic serologic reactions; (b) determine, retrospectively, the preseroconversion frequency of indeterminate WB assays in 286 men who seroconverted; and (c) evaluate in vitro production of specific antibody by peripheral blood mononuclear cells (PBMCs) as a method of indicating whether or not an indeterminate WB assay represents HIV-1 infection. Reactions to products of gag, pol, or env were noted in 8.0, 4.0, and 6.7% of 1,595 first-visit tests of men who remained seronegative for 4 years. Indeterminate reactions occurred in 204 men with negative EIAs who subsequently seroconverted and in 82 men with positive EIAs preconversion. Supernatants harvested from PBMCs of 2 of 36 seroconverters obtained one or two visits preseroconversion and cultured with pokeweed mitogen were antibody-positive. All were positive at the visit, with diagnostic serology. None of the supernatants from cells of 19 men with EIA-negative WB-indeterminate serologic assays were antibody-positive. Our results suggest that persistently EIA-negative homosexual/bisexual men who have indeterminate WB assays are unlikely to be infected with HIV-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Bisexuality↗
PubMed1992

Acquired immune deficiency syndrome occurring within 5 years of infection with human immunodeficiency virus type-1: the Multicenter AIDS Cohort Study.

The objective of this study is to describe participants in the Multicenter AIDS Cohort Study (MACS) with incident infection due to the human immunodeficiency virus type-1 (HIV-1) in whom AIDS developed by March 1990 and within 5 years of seroconversion (group A). Secondly, behavioral, clinical, and immunologic characteristics of these men are compared to those of matched seroconverters remaining AIDS free (group B). Between entry into the MACS (April 1984-March 1985) and July 1989, 345 seronegative homosexual/bisexual men had HIV-1 antibody; of these men, AIDS developed in 32 by March 1990. The Kaplan-Meier estimates of the proportion of men with incident HIV-1 infection with AIDS were 6 months, 0%; 12 months, 1%; 24 months, 3%; and 48 months, 10%. These 32 men engaged in receptive anal intercourse with more partners before (p less than 0.005) and after seroconversion (p less than 0.005) and reported more sexually transmitted disease preseroconversion (p = 0.05) than did group B. These findings suggest that sexually transmitted co-factors, preseroconversion and/or postseroconversion, play a role in the progression of HIV-1 infection. Alternatively, greater sexual activity could increase the hazard of exposure to a more virulent HIV-1 strain.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Human immunodeficiency virus isolates from asymptomatic homosexual men and from AIDS patients have distinct biologic and genetic properties.

Human immunodeficiency virus type 1 (HIV-1) isolates from asymptomatic homosexual men and AIDS patients were compared for their in vitro biologic and genetic properties. Most of the HIV-1 isolates from asymptomatic men, but not from AIDS patients, failed to infect CD4+ H9 cells and phytohemagglutinin-stimulated peripheral blood lymphocytes. In a longitudinal study, serial HIV-1 isolates obtained from men who seroconverted to HIV-1 and later developed AIDS were able to infect H9 cells. In contrast, longitudinal isolates from men who remained asymptomatic did not infect H9 cells. HIV-1 isolates from AIDS patients in general exhibited increased production of intracellular viral DNA, RNA, and protein as compared to isolates from asymptomatic men. Cells infected with HIV-1 isolates from asymptomatic men produced very little gp120, p24, and p55 proteins as compared to those from AIDS patients. The overall restriction patterns of HindIII, Sac-1, Pst-1, EcoR1, and BamH1 were very similar between HIV-1 isolates from asymptomatic men and those from AIDS patients. However, the restriction endonuclease pattern of BglII was quite distinct for isolates from asymptomatic men as compared to AIDS patients. Preliminary studies mapped a unique BglII site in the gag region of most of the isolates from asymptomatic men, approximately 2.0 kb from the 5' end. Thus, HIV-1 isolates from asymptomatic subjects and from AIDS patients have distinct biologic and genetic properties which may be related to the various clinical outcomes of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Augmentation of cellular immune function during the early phase of zidovudine treatment of AIDS patients.

Twenty-five patients with AIDS in AIDS Clinical Trials Group Protocol 002 were treated with either low or high dosages of zidovudine. This resulted in moderate, transient increases by 10 and 20 weeks in lymphocyte blastogenesis and interferon-gamma (IFN-gamma) production in vitro in response to phytohemagglutinin with and without recombinant interleukin-2. Immune responses to cytomegalovirus and herpes simplex virus type 1 antigens were augmented less frequently during therapy. Natural killer (NK) cell lysis of uninfected and human immunodeficiency virus-infected cells was also transiently increased by 10 and 20 weeks. IFN-gamma production, the only immune parameter directly associated with increases in numbers of CD4+ T cells, peaked at 10 weeks of treatment. The limited efficacy of zidovudine treatment in AIDS patients is associated with moderate, temporary increases in nonspecific and herpesvirus-specific T lymphocyte responses and NK cell function.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Prospective multicenter study on isolation of human immunodeficiency virus type 1 from homosexual men after seroconversion.

A prospective multicenter study was undertaken to isolate human immunodeficiency virus type 1 (HIV-1) from 45 homosexual men for a period of 30 months after seroconversion. Efficiency of HIV-1 isolation from peripheral blood mononuclear cells was relatively stable over time, ranging from 64% at the time of seroconversion to more than 82% after 18 months of seroconversion. However, Kaplan-Meier analysis of HIV-1 culture data indicates that the cumulative proportion of HIV-1 culture positivity at 3, 6, 12, and 18 months after seroconversion was 62, 65, 84, and 92%, respectively. No significant correlation was observed between the presence of HIV-1 p24 antigen in serum, or numbers of CD4+ and CD8+ blood lymphocytes, and HIV-1 isolation within this period of time. These data suggest that HIV-1 viremia in homosexual men gradually increases to almost 100% culture positivity by 18 months after seroconversion.

HIV Seropositivity↗
PubMed1990

The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS Cohort Study Group.

We assessed the risk of pneumonia due to Pneumocystis carinii in 1665 participants in the Multicenter AIDS Cohort Study who were seropositive for human immunodeficiency virus type 1 (HIV-1) but did not have the acquired immunodeficiency syndrome (AIDS) and were not receiving prophylaxis against P. carinii. During 48 months of follow-up, 168 participants (10.1 percent) had a first episode of P. carinii pneumonia. The risk was greatly increased in participants with CD4+ cell counts at base line of 200 per cubic millimeter or less (relative risk, 4.9; 95 percent confidence interval, 3.1 to 8.0). Although most participants (60.7 percent) described no HIV-1-related symptoms at the clinic visit at which a CD4+ cell count of 200 per cubic millimeter or less was first noted, this finding during follow-up was also associated with an increased risk of P. carinii pneumonia. The development of thrush or fever significantly and independently increased the risk of P. carinii pneumonia in these patients (adjusted relative risks, 1.86 and 2.15 for thrush and fever, respectively). Most participants with CD4+ cell counts above 200 per cubic millimeter who had P. carinii pneumonia within six months were symptomatic. We conclude that P. carinii pneumonia is unlikely to develop in HIV-1-infected patients unless their CD4+ cells are depleted to 200 per cubic millimeter or below or the patients are symptomatic, and therefore that prophylaxis should be reserved for such patients.

Adolescent↗
PubMed1990

A semiquantitative microassay for measurement of relative number of blood mononuclear cells infected with human immunodeficiency virus.

A simple semiquantitative microassay was developed for the measurement of relative number of infected peripheral blood mononuclear cells (PBMC) from individuals infected with human immunodeficiency virus (HIV). The assay is based on cocultivation of serially diluted PBMC of a seropositive person with phytohemagglutinin-stimulated normal PBMC. The microassay has comparable sensitivity with the standard virus culture method in detecting positive HIV cultures. Since the microassay uses only 2-3 x 10(5) patients' PBMC, the assay is also most suitable for HIV isolation from HIV-infected infants or from AIDS patients with extremely low T-cell counts. The microassay can also be used to measure antiviral effects of a drug on persistent HIV infection in vitro. Because the microassay measures the relative number of infected PBMC, it can be readily used for following the quantitative antiviral effect of a drug in a clinical trial.

AIDS-Related Complex↗
PubMed1990

Oxophenarsine, an antisyphilis drug inhibits HIV-1-specific protein synthesis in acutely and persistently infected lymphocytes.

The development of drugs that can inhibit both acute and persistent anti-human immunodeficiency virus type 1 (HIV-1) infection is a major goal in the treatment of patients with acquired immunodeficiency syndrome (AIDS). Most of the anti-HIV-1 drugs reported thus far, such as azidothymidine (AZT), inhibit acute HIV-1 infection but have no antiviral effect against persistent infection. We report here that oxophenarsine (3-amino-4 hydroxyphenylarsineoxide hydrochloride), an antisyphilus drug inhibits HIV-1 production in acutely infected peripheral blood lymphocytes (PBL) and persistently infected T cells. In acutely infected PBL and H9 T cells, the drug is effective at concentrations as low as 0.07-0.15 micrograms/ml with no significant cytotoxicity at concentrations of 6.0 micrograms/ml or below. It does not inhibit HIV-1 reverse transcriptase at doses up to 60 micrograms/ml. The drug has no effect on HIV-1-specific DNA and RNA synthesis. However, it inhibits HIV-1 protein synthesis in both acutely and persistently infected cells.

Anti-Infective Agents↗
PubMed1990

Serum IgG and IgA antibodies specific to Epstein-Barr virus capsid antigen in a longitudinal study of human immunodeficiency virus infection and disease progression in homosexual men.

A longitudinal study of serum IgG and IgA antibody titers to Epstein-Barr virus (EBV) viral capsid antigen (VCA) was carried out in 218 homosexual men at various stages of human immunodeficiency virus (HIV) infection. The serum samples tested were obtained from the following groups: 24 HIV seroconverters, 41 persistently HIV-seropositive asymptomatic individuals, 22 seropositives who developed AIDS-related complex (ARC), 29 HIV seropositives who developed lymphadenopathy syndrome (LAS), 35 HIV seronegatives with LAS, 36 asymptomatic HIV seronegatives, and 31 AIDS patients. Blind-tested samples were titrated for IgG and IgA EBV-VCA antibodies by immunoperoxidase assay (IPA). Cross-sectional analysis indicated that all HIV-seropositive subjects exhibited significantly elevated EBV IgG and IgA antibody titers compared with HIV-seronegative subjects. The proportions with EBV-VCA IgA antibodies at a titer of greater than or equal to 128 rose during the course of HIV infection and progression of the disease: 8% in HIV seronegatives, 11% in HIV seronegatives with LAS, 25% in HIV seronegatives prior to HIV seroconversion, 44% in asymptomatic HIV seropositives, 34% in LAS, 50% in ARC, and 58% in AIDS patients. An increase in EBV-VCA IgG and IgA titers was detected following HIV seroconversion and in samples obtained 6 months before disease progression to LAS. These data suggest the possible involvement of EBV in the natural history of HIV infection and disease progression. The possibility that EBV-VCA IgA antibody levels would be of value in prediction of progression of HIV-related illness is discussed.

AIDS-Related Complex↗
PubMed1989

Development of antibodies to HIV-1 is associated with an increase in circulating CD3+CD4-CD8- lymphocytes.

This study investigated whether seroconversion with respect to human immunodeficiency virus, type 1 (HIV-1) was associated with an increase in lymphocytes expressing the CD3+CD4-CD8- phenotype. Proportions and absolute numbers of CD3+, CD4+, and CD8+ lymphocytes were determined prospectively over a 2.5-year period on 4954 homosexual and/or bisexual men participating in the Multicenter AIDS Cohort Study. Of the 4808 men whose serostatus at entry could be verified, 1745 were seropositive (SP) for antibodies to HIV-1 at entry into study, 2795 were uniformly seronegative (SN) for HIV-1 for 30 months, and 268 were seroconverters (SC) with respect to HIV-1 during this period. For each of six semiannual evaluations, proportions and numbers of CD3+CD4-CD8- lymphocytes (calculated as CD3- (CD4 + CD8] were both significantly greater in the SP group than in the SN group (P less than 0.001). Mean CD3+CD4-CD8- levels in the SC group were indistinguishable from those in the SN group before seroconversion, but by 3-9 months after seroconversion the SC group demonstrated absolute numbers of CD3+CD4-CD8- lymphocytes which were significantly increased (P less than 0.001) compared to the SN group using linear regression methods with adjustment for correlation of measurements within an individual over time. An additional significant increase occurred by 21-27 months after seroconversion (P = 0.006). These results are consistent with an association of HIV-1 seroconversion with an increase in circulating T lymphocytes expressing the CD3+CD4-CD8- phenotype (double negative T cells), a decrease in CD3-CD4-CD8+ natural killer cells, or both. An increase in double negative T cells could reflect a host defense mechanism against HIV-1 or effects of HIV-1 on T cell development.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Up-regulation of natural killer activity of human immunodeficiency virus-infected patients by in vitro-differentiated macrophages.

Patients with acquired immunodeficiency syndrome (AIDS)-related complex and asymptomatic individuals seropositive for human immunodeficiency virus (HIV) have depressed natural killer (NK) activity. Normal human macrophages cultured for 3-7 days significantly up-regulated the NK activity of mononuclear cells obtained from the blood of asymptomatic HIV-seropositive individuals and patients with AIDS. Following a 4-hr incubation of patients' cells with in vitro-differentiated macrophages, the greatest augmentation of NK activity was seen in asymptomatic HIV-seropositive individuals who were receiving treatment with azidothymidine. Stimulation of macrophage immunoregulatory activities or adoptive immunotherapy with ex vivo-activated monocytes may be beneficial in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Association of human immunodeficiency virus (HIV) p24 antigenemia with decrease in CD4+ lymphocytes and onset of acquired immunodeficiency syndrome during the early phase of HIV infection.

Human immunodeficiency virus (HIV) p24 antigenemia was assessed in a longitudinal study of 52 homosexual men who developed serum antibody to HIV. Antibody seroconversion to HIV as defined by a positive HIV enzyme immunoassay (EIA) confirmed by Western (immuno-) blot was associated with three major patterns of HIV antigenemia. In the first pattern, a transient antigenemia was noted 6 (six subjects) and 12 (one subject) months prior to detection of antibody by HIV EIA and Western blot in 7 (13.5%) of the 52 men. Use of an EIA employing a recombinant envelope protein (ENV9) was able to detect antibody in four of these seven men at the time of this early antigenemia. In the second pattern, HIV p24 antigenemia occurred in 8 (15.4%) of the 52 subjects within the first 12 months after HIV antibody seroconversion. No p24 antigen was detected in the 37 (71.1%) remaining subjects. CD4+ cell numbers were lower in antigen-positive men before and after antibody seroconversion. Development of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was strongly associated with evidence of persistent p24 antigenemia during the early, postseroconversion period. HIV p24 antigenemia may be of value in determining appropriate cohorts for drug therapy trials for subjects with early-phase HIV infection.

AIDS-Related Complex↗
PubMed1989

Cell-to-cell transmission of human immunodeficiency virus type 1 in the presence of azidothymidine and neutralizing antibody.

Very few peripheral blood lymphocytes of seropositive individuals are presumably actively infected with human immunodeficiency virus type 1 (HIV-1). During coculture of lymphocytes of a seropositive individual with mitogen-stimulated normal peripheral blood lymphocytes, the number of infected cells becomes amplified such that detectable HIV-1 is produced. We report here that in addition to transmission by extracellular virus, cell-to-cell transmission is responsible for spreading HIV-1 infection from infected to uninfected cells. Azidothymidine and virus-neutralizing antibody had no effect on cell-to-cell transmission of HIV-1. Monoclonal antibodies to the CD4 receptor, but not to the CD3 receptor, prevented cell-to-cell transmission, which suggests that CD4 receptor-mediated cell fusion is involved in cell-to-cell transmission. Spread of infection in a cell-to-cell manner may be important in development of drug therapies for HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

HIV-1-specific production of IFN-gamma and modulation by recombinant IL-2 during early HIV-1 infection.

Specific cellular immune responses to human immunodeficiency virus type 1 (HIV-1) were assessed in mononuclear leukocyte cultures from homosexual men with documented, early phase HIV-1 infection. Cell cultures from men with a mean duration of 1.3 yr (range, 0.3 to 2.2 yr) of HIV-1 infection were treated with UV-inactivated, whole, purified HIV-1 Ag together with various concentrations of rIL-2. Cell supernatants were harvested after 5-day incubation and assayed for IFN activity against encephalomyocarditis virus in human WISH cells. IFN subtypes were characterized by neutralization of antiviral activity with antiserum specific for human IFN-gamma and IFN-alpha. Results showed that cultures from 68% (17 of 25) of the HIV-1-seropositive subjects produced "immune" IFN-gamma in response to whole HIV-1 Ag plus rIL-2. IFN-gamma was induced in only 20% (5 of 25) of cultures treated with HIV-1 Ag alone. Enhancement of HIV-1-specific IFN-gamma production by rIL-2 was synergistic rather than additive in that titers induced by the mixture were consistently higher than the sum of IFN titers induced by HIV-1 or rIL-2 alone. This effect was not demonstrable in cultures from 18 HIV-1-seronegative men. Similarly, HIV-1-immune specific augmentation of IFN-gamma production by rIL-2 was noted for PENV9, a recombinant HIV-1 envelope glycoprotein gp41 and gp120 fragment. Production of IFN-gamma may be an important, HIV-1-immune specific parameter in the host response to this retrovirus.

Acquired Immunodeficiency Syndrome↗