Search PubMed⌕ Search

Biomedical subjects

C R Rinaldo

Publications and source records attributed to C R Rinaldo.

At least 55 records · Page 3Linked to original sources
PubMed1996

Occurrence of cytomegalovirus retinitis after human immunodeficiency virus immunosuppression.

OBJECTIVE: To estimate the incidence and prevalence of cytomegalovirus retinitis (CMV-R) in late-stage human immunodeficiency virus type 1 disease. DESIGN: Cohort study. SETTING: The Multicenter AIDS Cohort Study, an ongoing 10-year study of human immunodeficiency virus type 1-infected homosexual men with semiannual visits and CD4+ cell testing. STUDY PARTICIPANTS: Three hundred sixty-seven human immunodeficiency virus type 1-infected men from the Multicenter AIDS Cohort Study who were receiving zidovudine and Pneumocystis carinii prophylaxis and who had CD4+ cell counts fall below 0.10 x 10(9)/L (100/microL). MAIN OUTCOME MEASURES: Kaplan-Meier-type estimates for various longitudinal quantifications of incidence and prevalence of CMV-R were obtained. RESULTS: Among these 367 individuals, cytomegalovirus disease developed in 103, of whom 73 (71%) had ocular complications. At 4 years after the first CD4 cell count ( < 0.10 x 10(9)/L), the probability for these subjects to have (1) remained living without CMV-R was 11%, (2) died without experiencing CMV-R was 66%, (3) experienced CMV-R and be living was 6%, and (4) experienced CMV-R and died was 18%. During these 4 years, there was a 25% chance for the development of CMV-R and, on average, 0.211 person-years of CMV-R morbidity. Among those subjects in whom CMV-R developed, about 19% did have CMV-R before a CD4+ cell count of less than 0.05 x 10(9)/L ( < 50/microL) was observed, and 81% had CMV-R after the CD4+ cell count reached this threshold. CONCLUSION: These estimates may be relevant to current clinical practice and help in allocating resources and planning for treatment and prophylaxis against cytomegalovirus disease.

AIDS-Related Opportunistic Infections↗
PubMed1996

KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma.

A major controversy regarding Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) is whether or not it is a ubiquitous infection of humans. Immunoassays based on KSHV- and Epstein-Barr virus (EBV)-coinfected cell lines show that most US AIDS-KS patients have specific antibodies to KSHV-related antigens. We have developed a sensitive indirect immunofluorescence assay (IFA) based on an EBV-negative, KSHV-infected cell line, BCP-1. When we used this IFA assay, KSHV-related antibodies were found in 71-88% of serum samples from US, Italian and Ugandan AIDS-KS patients, as well as all serum samples examined from HIV-seronegative KS patients. Although none of the US blood donors examined were KSHV seropositive by IFA, intermediate and high seroprevalence rates were found in Italian and Ugandan control populations. Antibody kinetics showed that more than half of the AIDS-KS patients who were examined IgG-seroconverted before KS development, and antibody levels did not decline after seroconversion. For these patients, seropositivity rates increased linearly with time, suggesting that the rate of infection was constant and that the risk of developing KS once infected with KSHV is not highly dependent on the duration of infection. These data strongly suggest that KSHV is not ubiquitous in most populations and that the virus may be under strict immunologic control in healthy KSHV-infected persons.

AIDS-Related Opportunistic Infections↗
PubMed1996

Hepatitis C virus infection in a male homosexual cohort: risk factor analysis.

BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of morbidity throughout the world. Parenteral exposure to infected blood accounts for the majority of cases. Sexual transmission is suggested by the higher prevalence of infection in sex workers and homosexual men. Sexual practices which contribute to HCV infection need to be identified. METHODS: The social and medical history, and HCV serostatus of 1058 homosexual men in the Pittsburgh arm of the Multicenter AIDS Cohort Study were analysed. Multivariate analysis was used to determine risk factors for HCV seropositivity. RESULTS: 31 men were HCV seropositive by enzyme immunoassay and recombinant immunoblot assay (2.9%). They were more likely to be HIV seropositive (39%) than the HCV seronegative men (19%). Needle sharing and illegal drug use were the most important risk factors for HCV seropositivity. Statistically significant sexual factors (p < 0.05) included a history of syphilis, rectal gonorrhea, anal insertive intercourse with ejaculation, and douche or enema use before anal receptive intercourse. The number of sexual partners was not a significant risk factor. CONCLUSIONS: HCV infection is associated with specific sexually transmitted diseases (STDs) and sexual practices in the male homosexual population. The evidence of high risk behavior should be incorporated into ongoing educational efforts to decrease the incidence of STDs.

Adult↗
PubMed1995

Long-term survivors with HIV-1 infection: incubation period and longitudinal patterns of CD4+ lymphocytes.

To characterize long-term survival with HIV-1, we need to estimate the proportion of seroconverters remaining free from clinical AIDS for long periods. We predict that approximately 13% of homosexual/bisexual men infected at a young age may remain so for > 20 years. Since studies have not followed individuals for such periods, long-term survivors must be characterized using stability of immunologic markers. In a cohort of 1,809 seropositive men followed since 1984-85, 15% (187/1,214) of those with at least two consecutive visits early in the study showed no decline in CD4+ cell count. From these, 67 men with long follow-up and no use of zidovudine were identified as cases to investigate correlates of protection against HIV-1-induced immunodepletion. Two matched control subgroups, one with moderate and one with rapid CD4+ lymphocyte decline, produced 56 triplets of individuals to be contrasted. Analysis of data from early in the study on demographics, sexual behavior, and sexually transmitted diseases revealed no significant differences among the three groups. Men showing no decline in CD4+ lymphocytes persistently showed a healthier profile with respect to onset of clinical AIDS, survival, and concomitant hematologic variables. Moderate decliners had rates of clinical AIDS and death significantly higher than those in the stable group but lower than the fast decliners.

CD4 Lymphocyte Count↗
PubMed1995

Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion.

OBJECTIVE: To investigate the relation between the quantity of human immunodeficiency virus type 1 (HIV-1) RNA in plasma and the risk for the acquired immunodeficiency syndrome (AIDS) or a decline in the CD4+ T-cell count after seroconversion. DESIGN: Prospective study. PATIENTS: 62 homosexual men with documented HIV-1 seroconversion. SETTING: University outpatient setting. MEASUREMENTS: Clinical status, CD4+ T-cell counts, and plasma and serum samples were obtained every 6 months. Human immunodeficiency virus RNA in plasma was quantitated with a branched-DNA (bDNA) assay. Serum samples were assayed for neopterin, beta 2-microglobulin, and immune complex dissociated HIV-1 p24 antigen. RESULTS: 18 of 62 (29%) men developed AIDS; 21 (34%) had a significant decline in the CD4+ T-cell count without AIDS; and 23 (37%) had a stable CD4+ T-cell count. For each participant, HIV-1 RNA results were categorized into one of four groups: 1) detection of HIV-1 RNA (> 1 x 10(4) genome equivalents/mL [Eq/mL]) in all samples; 2) detection in most samples (> or = 50%); 3) detection in fewer than 50% of samples; and 4) detection in none of the samples. Detection of HIV-1 RNA in all or most samples was strongly associated with AIDS (16 of 18 patients) and a decline in the CD4+ T-cell count (13 of 21 patients) compared with a stable CD4+ T-cell count (4 of 23 patients; P < 0.001). Conversely, the absence of HIV-1 RNA (< 1 x 10(4) Eq/mL) in all or most samples was associated with stable CD4+ T-cell counts (19 of 23 patients) and a lower risk for AIDS or decline in the CD4+ T-cell count (10 of 39 patients; P < 0.001). In multivariate analysis of all laboratory values at the seroconversion visit, a plasma HIV-1 RNA level greater than 1 x 10(5) Eq/mL was the most powerful predictor of AIDS (odds ratio, 10.8; P = 0.01). CONCLUSIONS: Plasma HIV-1 RNA is a strong, CD4+ T-cell-independent predictor of a rapid progression to AIDS after HIV-1 seroconversion.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Comparison of monoclonal antibodies for immunostaining in the cytomegalovirus shell vial assay on 4,388 specimens.

The shell vial assay is a sensitive, rapid test for the detection of cytomegalovirus (CMV) in a variety of specimens. The sensitivity of this assay is dependent on a number of factors including the antibodies used for immunostaining. Monoclonal antibodies to the CMV major immediate-early antigen (p72) from Chemicon (MAB810) and Dupont (NEA-9221) were assessed side by side in duplicate vials on 4,388 specimens from a patient population consisting of > 90% organ transplant recipients. A total of 240 specimens (5.5%) were CMV positive in either one or both vials. Positivity rates were variable across different specimen types but highest (12.9%) in urine specimens. Of the positive specimens, 175 (72.9%) tested positive in both vials, 43 (17.9%) tested positive in the Chemicon-stained vial only, and 22 (9.2%) tested positive in the Dupont-stained vial only (P < 0.01, McNemar's chi-square test). This gave an overall positivity rate of 5.0% for Chemicon antibodies and 4.5% for Dupont. There was no difference in the fluorescent focus counts produced by the two antibody sets. It is concluded that use of the Chemicon antibodies provides increased sensitivity of detection of CMV in the shell vial assay above that afforded by the Dupont antibody.

Antibodies, Monoclonal↗
PubMed1995

Apoptosis parallels lymphopoiesis in bone marrow transplantation and HIV disease.

Apoptosis has been implicated in a variety of physiological processes ranging from tissue modeling to deletion of autoreactive T lymphocytes during thymic development. The recent finding that a large proportion of peripheral T cells from HIV-infected subjects (corrected from subjects) apoptose in culture raises an important issue: does this represent a pathologic mechanism by which the virus disrupts the immune system, or a normal physiologic response to virus-mediated T-cell loss? To study the potential relationship between apoptosis and lymphopoiesis, we compared apoptosis rates in unstimulated lymphocyte cultures from healthy subjects, HIV+ gay men, and bone marrow transplant (BMT) recipients undergoing immune reconstruction. BMT recipients were chosen because they undergo massive regeneration of lymphocytes following marrow ablation and graft infusion. The data obtained in BMT recipients suggests that elevated apoptosis accompanies, and is the consequence of, elevated lymphopoiesis. We also found a strong inverse relationship between in vitro T-cell apoptosis rates and peripheral T-cell counts. These results provide new interpretation for elevated apoptosis observed in HIV-infected individuals--that it reflects increased T-cell turnover consequent to virus-mediated destruction of CD4+ T-cells.

Apoptosis↗
PubMed1995

Anti-HIV type 1 cytotoxic T lymphocyte effector activity and disease progression in the first 8 years of HIV type 1 infection of homosexual men.

Cytotoxic T lymphocytes (CTL) may play an important role in host defense against HIV-1 infection. In this study, we examined the responses of circulating effector CTL (CTLe) specific for Gag, Pol, Env, and Tat in 57 HIV-1-infected men, 49 of whom were asymptomatic and had documented time since seroconversion of < 8 years. CTLe responses to at least one of the four HIV-1 gene products were detected in 83% of the subjects. The magnitude and prevalence of the anti-Tat responses were significantly less than the responses to Gag, Pol, and Env. Cell depletion studies indicated that the lytic activity against the HIV-1 structural proteins was mediated by CD8+ T cells, although 30% of Env-specific lysis was mediated by CD16+ natural killer cells. Anti-HIV-1 CTLe responses against Gag and Pol were significantly less in subjects infected for over 6 years as compared to those infected for shorter periods of time. We found no correlation, however, between anti-HIV-1 CTLe responses and either CD4+ or CD8+ T cell counts, rates of CD4+ T cell loss, HIV-1 infectious viral load, use of antiviral medications, or subsequent progression to AIDS. Our results indicate that anti-HIV-1 CTLe activity is relatively stable in asymptomatic subjects infected < 6 years, and is not an early marker for risk of disease progression.

Adult↗
PubMed1995

T cell proliferative responses to five human cytomegalovirus proteins in healthy seropositive individuals: implications for vaccine development.

Cell-mediated immunity plays an important role in the host response against human cytomegalovirus (HCMV) infection. For the development of HCMV subunit vaccines it is essential to identify which HCMV proteins can induce protective immune responses in humans. We have studied the T cell proliferative responses to five HCMV proteins (IE1, IE2, pp71, gpUL18 and gB). These five proteins were produced using the maltose-binding protein (MBP) fusion protein system. T cell proliferative responses in 23 seropositive and six seronegative individuals were evaluated. None of the six seronegative individuals showed significant responses to any of the proteins. Of the 23 seropositive individuals, five responded to all five proteins, 14 responded to between one and four proteins and four responded to none of the proteins. The most commonly recognized proteins were gB (17/23, 74%) and IE2 (16/23, 70%). pp71 and IE1 were recognized by 10 of 23 (43%) individuals. Nine of 22 (41%) individuals tested responded to gpUL18, providing evidence that this protein is produced during infection. Our data indicate that a subunit vaccine composed of gB alone may not be sufficient to induce protective immunity in all individuals. The combination of two or three proteins may be more efficient as a potential vaccine.

Capsid↗
PubMed1995

Incidence of human immunodeficiency virus-related and nonrelated malignancies in a large cohort of homosexual men.

PURPOSE: To determine if the rates of malignancies other than Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) are increased in human immunodeficiency virus (HIV)-infected homosexual men. SUBJECTS AND METHODS: From 1984 through 1993, 1,199 homosexual men were studied in the Pittsburgh component of the Multicenter AIDS Cohort Study (MACS), an examination of the natural history of HIV infection. The cohort consisted of 769 HIV-seronegative (SN) participants and 430 seropositive (SP) members who were either seroprevalent at the time of enrollment or who seroconverted during the study. Cancer incidence data were collected through semiannual visits, phone interviews, medical records, and death certificates. Five thousand seven hundred eight person-years and 2,344 person-years were contributed to the study by the SN and SP men, respectively. RESULTS: In addition to 44 cases of KS, 13 NHLs, and 3 CNS lymphomas (CNSLs), 27 other malignancies occurred (three nonmelanoma skin cancers and eight other malignancies in the SP group, eight nonmelanoma skin cancers, and eight other malignancies in the SN group). Age-adjusted rates were calculated for both groups and compared with each other and with rates for the general male population in Pennsylvania. There were no differences between the SN group and the general population. Among the SP group, the combined frequency of all cancers other than KS, NHL, CNSL, and nonmelanoma skin cancers was statistically significantly increased in comparison to both the SN group and the general population. This increase was secondary to an unusually increased frequency of both seminoma and Hodgkin's disease. CONCLUSION: These findings support the hypothesis that the incidences of cancers other than KS and lymphoma are moderately increased in the setting of HIV infection and immunosuppression.

Adolescent↗
PubMed1994

CD4+ blood dendritic cells are potent producers of IFN-alpha in response to in vitro HIV-1 infection.

We determined the relative abilities of cell subpopulations from all major PBMC lineages of normal donors to produce IFN-alpha in response to in vitro stimulation with lymphocytotropic HIV-1 (IIIb and RF), monocytotropic HIV-1 (BaL), Sendai virus, and HSV-1. Active and inactive cell-free preparations of HIV-1 IIIb and cell-associated HIV-1 IIIb, and active cell-free preparations of the other viruses, induced comparable, maximal levels of acid-stable IFN-alpha in PBMC by 18 to 24 h. Negative selection and enrichment experiments indicated that HLA-DR+ "null" cells produced the majority of the IFN-alpha. A positive selection protocol using flow cytometric sorting enriched these HLA-DR+ CD3- CD19- CD16- CD56- CD14- cells to > 95% purity. These were identified as dendritic cells by their phenotype, large size, and veiled and ruffled morphology. The purified dendritic cells produced as much as 60-fold more IFN-alpha compared with purified, HLA-DR+ CD14+ monocytes in response to the viruses. IFN-alpha was not produced by CD3+ T cells or CD56+ NK cells. Purified CD19+ B cells produced a minimal amount of IFN-alpha in response to Sendai virus, and no IFN-alpha in response to the other viruses. Of significance, the dendritic cells expressed CD4 at a density similar to monocytes, and induction of IFN-alpha by HIV-1 could be blocked by HIV-1 gp120 anti-serum or anti-CD4 mAb. We conclude that the production of IFN-alpha constitutes a previously unrecognized major function of blood dendritic cells. This may be a mechanism of innate immunity mediated by dendritic cells against HIV-1 and other viral infections.

CD4 Antigens↗
PubMed1994

A phase I study of subcutaneous recombinant interleukin-2 in patients with advanced HIV disease while on zidovudine.

OBJECTIVE: A Phase I study of subcutaneous recombinant interleukin-2 (rIL-2). DESIGN: Sixteen patients with advanced HIV infection receiving 600-1200 mg zidovudine per day were divided into three groups, which received sequentially 0.2 x 10(6), 0.7 x 10(6) or 2 x 10(6) units/m2 per day of rIL-2 subcutaneously 5 consecutive days. SETTING: Five-day admission to an academic tertiary care hospital. PATIENTS, PARTICIPANTS: Sixteen unblinded, non-randomized volunteers. INTERVENTIONS: Subcutaneous rIL-2. MAIN OUTCOME MEASURES: Tolerance, toxicity, hematologic, immunologic and antiviral responses. RESULTS: rIL-2 was well-tolerated at the highest dosage, except in two patients who developed significant lymphopenia by the second day of rIL-2 administration, with rebound within 48 h after rIL-2 therapy. The number of eosinophils, CD4+ and CD8+ cells, and percentage of CD16+ (natural killer) cells, remained elevated above baseline for up to 10 weeks. Circulating rIL-2 receptor levels increased transiently during and immediately following rIL-2 administration. A twofold increase in natural killer cell activity against uninfected and HIV-infected targets was observed, but did not persist beyond 10 weeks following rIL-2 administration. There was a transient decrease in blastogenesis to phytohemagglutinin of patients receiving the highest dose of r-IL-2, but no significant change in viral burden. CONCLUSIONS: Subcutaneous rIL-2 in advanced HIV-infected patients on zidovudine was tolerated with side-effects similar to intravenous IL-2.

Adult↗
PubMed1994

The T-cell receptor V beta repertoire in naive and human immunodeficiency virus-1 (HIV-1) infected chimpanzees.

Using a panel of human T-cell receptor (TCR) variable region beta chain (V beta) polymerase chain reaction (PCR) primers, we performed cross-sectional and longitudinal analyses of the TCR V beta repertoire in naive and HIV-1 infected chimpanzees. We demonstrate that our TCR PCR primer panel will support amplification of chimpanzee cDNA from most of the TCR V beta families. However, no differences in TCR V beta expression were found between the naive and HIV-1 infected chimpanzees, unlike the TCR V beta repertoire perturbation found in HIV-1 infected human subjects. This finding suggests that a complete TCR repertoire in HIV-1 infected chimpanzees is associated with the maintenance CD4+ T-cell numbers and lack of progression to AIDS.

Animals↗
PubMed1994

Effects of enhancing agents on detection of cytomegalovirus in clinical specimens.

Dimethyl sulfoxide, dexamethasone, and calcium were tested in combination for their enhancing effects on cytomegalovirus detection in shell vial cultures on 1,579 clinical specimens obtained primarily from adult solid-organ transplant recipients. Fluorescent-focus counts were elevated for the cytomegalovirus-positive urine specimens (P < 0.01) and throat washings (P < 0.05) but not for the tissue biopsy or blood samples. Epidermal growth factor also increased focus counts but provided no additional benefit when used in combination with the other agents. The triple-combination treatment did not increase the number of positive specimens identified.

Adult↗
PubMed1994

Resistance to HIV-1 infection. Multicenter AIDS Cohort Study.

Men from the Multicenter AIDS Cohort Study were classified as "susceptible" and "resistant" to HIV infection. Resistant men were still HIV antibody negative in 1993 and were estimated to have had > 45 different anal intercourse partners (median, 92; range, 46-504) in the 2.5 years before visit 2 (1985). Susceptible men were seroconverters who were estimated to have had < 13 different anal partners (median, 4; range, 0-12). Leukocyte groups were compared between the two groups of men. Values were excluded for 12 months before the first antibody-positive visit in the susceptible men. White blood cells, polymorphonuclear neutrophils, total lymphocyte count, CD8+ percentage and number, and CD3+ and CD4+ number were higher in the resistant men. Logistic regression analyses were used to develop 50 bivariate models. Higher levels of neutrophils and CD8+ cells were included in four of the six best-fitting bivariate models, suggesting that each is associated with resistance to HIV-1 infection. These results support the hypothesis that CD8+ cells may modulate the outcome of HIV-1 exposure.

CD8-Positive T-Lymphocytes↗
PubMed1994

Detection of cytomegalovirus in formalin-fixed paraffin-embedded donor, native and allograft liver tissue using a multiplex polymerase chain reaction-liquid hybridization assay.

A multiplex polymerase chain reaction (PCR)-liquid hybridization assay detecting a minimum 10 fg of cytomegaloviral (CMV) DNA has been developed. This assay successfully detected viral nucleic acids in 25/26 (96.2%) routinely embedded allograft liver biopsies with CMV hepatitis. No CMV DNA was detected in 15 native and 12 donor liver tissues sampled at the time of liver transplantation. These results indicate that archived formalin-fixed, paraffin-embedded liver tissues obtained from patients with significant liver disease can be successfully analyzed for CMV by PCR, retrospectively. Failure to detect CMV in native and donor livers implies that any latent virus present within these tissues is very focally distributed, or is below the threshold of detection applicable to PCR.

Base Sequence↗