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T J Spira

Publications and source records attributed to T J Spira.

At least 19 recordsLinked to original sources
PubMed1996

Seroconversion to antibodies against Kaposi's sarcoma-associated herpesvirus-related latent nuclear antigens before the development of Kaposi's sarcoma.

BACKGROUND: If Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi's sarcoma, serologic evidence of infection should be present in patients before the disease develops. METHODS: Using an immunoblot assay for two latent nuclear antigens of KSHV, we tested serum samples from homosexual male patients with the acquired immunodeficiency syndrome (AIDS) with and without Kaposi's sarcoma (HIV-infected men with hemophilia), HIV-seronegative blood donors, and HIV-seronegative patients with high titers of antibodies against Epstein-Barr virus (EBV). Serial serum samples obtained from patients with Kaposi's sarcoma before the diagnosis of the disease were tested for evidence of seroconversion. RESULTS: Of 40 patients with Kaposi's sarcoma, 32 (80 percent) were positive for antibodies against KSHV antigens by the immunoblot assay, as compared with only 7 of 40 homosexual men (18 percent) without Kaposi's sarcoma immediately before the onset of AIDS. Of 122 blood donors, 22 EBV-infected patients, and 20 HIV-infected men with hemophilia, none were seropositive. When studied by the immunoblot assay over a period of 13 to 103 months, 21 of the 40 patients with Kaposi's sarcoma (52 percent) seroconverted 6 to 75 months before the clinical appearance of Kaposi's sarcoma. The median duration of antibody seropositivity for KSHV-related latent nuclear antigens before the diagnosis of Kaposi's sarcoma was 33 months. CONCLUSIONS: In most patients with kaposi's sarcoma and AIDS, seroconversion to positivity for antibodies against KSHV-related nuclear antigens occurs before the clinical appearance of Kaposi's sarcoma. This supports the hypothesis that Kaposi's sarcoma results from infection with KSHV.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Mechanisms of human immunodeficiency virus Type 1 (HIV-1) neutralization: irreversible inactivation of infectivity by anti-HIV-1 antibody.

An assay for the neutralization of human immunodeficiency virus type 1 (HIV-1) is described in which the reduction in infectious titer of HIV-1 after preincubation at 37 degrees C with antibody-positive serum is the measure of neutralization. The assay format and its controls allow several experimental manipulations that, taken together, indicate an effect of antibody on HIV-1 infectivity that occurs before or independently of HIV-1 attachment. The direct inactivation of HIV-1 infectivity by antibody is irreversible and temperature dependent, requires a bivalent antibody directed against accessible envelope determinants, and does not require a heat-labile or (Ca2+)- or (Mg2+)-dependent cofactor. The mechanism of inactivation cannot be explained by agglutination of virus, nor is it associated with disruption or dissociation of envelope protein from virions. Rather, the antibody is likely to perturb some metastable property of the envelope that is required for entry. Laboratory-adapted HIV-1 isolates were more sensitive to the inactivating effects of sera than were primary patient isolates. The latter were particularly resistant to inactivation by contemporary autologous sera, a feature not explained by blocking antibodies. Additional studies showed a weak relationship between disease course and serum inactivation of the reference LAI laboratory strain of HIV-1. Heteroduplex analysis and autologous inactivation assays of sequential specimens from individual patients indicate that over time, the viral quasispecies that emerge and dominate are resistant to the inactivating effects of earlier sera.

Animals↗
PubMed1995

Is Kaposi's-sarcoma-associated herpesvirus detectable in semen of HIV-infected homosexual men?

We explored a possible route of transmission of Kaposi's-sarcoma-associated herpes virus (KSHV) with nested and unnested PCR techniques. We looked for KSHV DNA sequences in semen of HIV-positive homosexual men and HIV-negative healthy semen donors. With unnested primers we found KSHV sequences in 21 of 33 (64%) homosexual men and in none of 30 healthy donors. With a nested PCR assay, 30 of 33 (91%) specimens from the homosexual men and 7 of 30 (23%) specimens from healthy donors had detectable KSHV sequences. Over 5 years of follow-up, 13 of 30 KSHV-positive homosexual men (43%) developed KS compared with none of the 3 KSHV-negative homosexual men.

DNA, Viral↗
PubMed1995

Detection of reverse transcriptase by a highly sensitive assay in sera from persons infected with human immunodeficiency virus type 1.

In an ultrasensitive assay for reverse transcriptase (RT), an in vitro-transcribed heteropolymeric RNA sequence was used as a template and polymerase chain reaction (PCR) amplification with Southern blot hybridization served as a detection system for the cDNA reaction product. The assay, called Amp-RT, detected 9 tested retroviruses in unconcentrated culture supernatants diluted 10(2)- to 10(5)-fold. A comparative analysis using human immunodeficiency virus type 1 (HIV-1) revealed that Amp-RT was 100,000 times more sensitive than the standard RT assay, 10,000 times more sensitive than p24 antigen capture and branched DNA assays, and 100 times more sensitive than RT-PCR or TCID50 assays. Analysis of serum specimens from 42 HIV-1-infected persons by Amp-RT showed that 36 samples (85.7%) were RT-positive. In contrast, 41 serum specimens from persons seronegative for HIV-1 and human T lymphotropic virus types I and II were all Amp-RT-negative.

Animals↗
PubMed1995

CD4+ T lymphocytopenia in children: lack of evidence for a new acquired immunodeficiency syndrome agent.

We investigated children with CD4+ T lymphocytopenia to determine the magnitude and public health impact of this condition and to investigate possible causes. Children < 13 years old with CD4+ T lymphocyte counts below age-adjusted cutoffs (age < 24 months, 1000 cells/microliters; age > or = 24 months, 300 cells/microliters) or < 20% on 2 separate measurements were considered to have CD4+ T lymphocytopenia. We solicited information from clinicians and public health departments on these children and their families and collected blood for immunologic and retroviral testing. We identified 18 children (10 boys; 14 African-Americans) with a median age of 10 months at their first low CD4+ T lymphocyte measurement. Three children had had opportunistic infections and two still had low CD4+ T lymphocyte counts 5 and 7 years later. Of the 11 children born to human immunodeficiency virus (HIV)-infected mothers 7 were asymptomatic. Specimens from all children were negative for HIV and human T lymphotropic virus antibodies and negative for HIV by culture or polymerase chain reaction. Among 12 families interviewed no other HIV-seronegative family or household member had illnesses suggestive of immunosuppression. We conclude that negative retroviral tests and lack of illness among their family members do not support the hypothesis that a retrovirus causes CD4+ T lymphocytopenia among these children.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗
PubMed1994

Subpopulations of T and B cells in perinatally HIV-infected and noninfected age-matched children compared with those in adults.

Peripheral blood mononuclear cells were quantified for the subsets of CD4, CD8, and CD19 lymphocytes by using CD45RA (2H4), CD29(4B4), CD57, CD5, CD10, Leu8, HLA-DR, and TCR gamma delta-1 monoclonal antibodies and dual color immunofluorescence. A comparative analysis of lymphocyte subpopulations was made among 52 HIV-infected and 50 age-matched control children and 30 HIV-seropositive and 27 negative control adults. A significant decrease in the CD4+CD45RA+ "naive" cells was much more marked in HIV-infected children than in HIV-infected adults. A significant percentage increase in the CD4+CD29+ "memory" cells was observed in HIV-infected children but not in infected adults; however, the absolute numbers were usually decreased in all age groups. The mean percentage and absolute numbers of CD4+CD7+ and CD4+Leu8+ cells were decreased in HIV-infected children, although usually not significantly. The CD3+TCR gamma delta-1+ did not show any change in the infected children tested. The mean percentage and absolute number of the CD8+HLA-DR+ cells increased significantly in HIV-infected persons of all ages. The CD8+CD57+ cells were increased in percentage and absolute number in HIV-infected children ages 1-4 and 4-8 years. In the adults, no change was noted in either the percentage or absolute number of CD19+CD5+ B cells, a finding similar to that noted in HIV-infected children above 1 year of age. Although adults showed a significant decrease in both percentage and numbers of CD5- B cells, an increase was noted in the 7- to 12-month-old HIV-infected children. The CD19+CD10+ cells showed a slight but significant decrease in the youngest age group and a significant increase in the older age groups of HIV-infected children. These findings indicate that several lymphocyte subpopulations are altered differentially during HIV infection in children of varying ages and in adults.

Adult↗
PubMed1994

Idiopathic CD4+ T-cell lymphocytopenia with verrucae, basal cell carcinomas, and chronic tinea corporis infection.

Idiopathic CD4+ T lymphocytopenia should be considered in HIV-negative patients with skin lesions commonly associated with HIV infection. Patients with idiopathic CD4+ T lymphocytopenia are presumably rare, often have dermatologic lesions, always have low CD4+ T lymphocyte counts, and lack all evidence of HIV-1 infection. We describe a young man with verrucae, basal cell carcinomas, chronic tinea corporis, and laboratory evidence supporting a diagnosis of idiopathic CD4+ T lymphocytopenia.

Adult↗
PubMed1993

Protein S deficiency in men with long-term human immunodeficiency virus infection.

Decreases in protein S levels have recently been reported in some human immunodeficiency virus (HIV)-infected patients. To examine predisposing factors, 25 men randomly selected from a long-term study of HIV-infected patients were studied. The minimum mean duration of HIV seropositivity in this group was 106.6 months (range 15 to 143 months). No patients were anticoagulated at the time of the study. Three of the 25 randomly selected patients gave a history of thrombosis, in each instance occurring after the onset of HIV positivity. Two of the 3 patients with thrombosis had more than one episode. Coagulation studies showed that 3 of 3 (100%) of the patients with thrombosis and 16 of 22 (72.7%) of those without previous thrombosis had decreased free protein S. Mean-free and total protein S levels were statistically lower for HIV-infected patients with and without previous thrombosis compared with healthy male controls. C4b-binding protein was not increased in study patients with decreased protein S levels. Decreases in protein S levels did not correlate with CD4+ cell levels, CDC class, p24 antigen positivity, zidovudine (AZT) use, or Pneumocystis carinii prophylaxis. The duration of disease statistically correlated with decreases in protein S levels (r = .37, P < .05). A linear correlation existed between increasing IgG anticardiolipin antibody levels and decreasing free protein S antigen (r = .67, P < .005). This study shows that protein S deficiency is common in long-term HIV-infected patients and is caused by a decrease in the free protein, rather than by changes in the bound complex. The data suggest that protein S deficiency is not correlated with HIV disease severity but may predispose patients to thromboembolic complications.

Adult↗
PubMed1993

Idiopathic CD4+ T-lymphocytopenia--an analysis of five patients with unexplained opportunistic infections.

BACKGROUND: Although patients with idiopathic CD4+ T-lymphocytopenia and serious opportunistic infections have been described previously, the clinical and immunologic features of this condition have not been well defined. METHODS: We studied in detail five patients with idiopathic CD4+ T-lymphocytopenia. The studies included serologic testing, culture, and polymerase chain reaction for the human immunodeficiency virus (HIV) types 1 and 2, serologic testing for the human T-cell lymphotropic virus (HTLV) types I and II, lymphocyte phenotyping, immunoglobulin quantitation, and lymphocyte-transformation assays, as well as attempts to isolate a retroviral agent. The results were compared with those in HIV-infected persons matched for CD4+ T-cell counts and with those in normal controls. We also studied the spouses of patients and the blood donors for one patient. RESULTS: In these five patients, there was no evidence of either HIV or HTLV infection. All the patients had both low percentages and low counts of CD4+ T cells, with relative increases in percentages, but not counts, of CD8+ cells. Numbers of B cells and natural killer cells were generally normal. As compared with HIV-infected persons, our patients had lower percentages and counts of CD8+ cells and more lymphopenia. CD4+ counts were relatively stable over time. Instead of the high immunoglobulin levels seen in HIV infection, these patients had normal or slightly low levels of immunoglobulins. The lymphocyte-transformation response to mitogens and antigens was depressed. Results in spouses and blood donors were normal. CONCLUSIONS: Idiopathic CD4+ T-lymphocytopenia differs from HIV infection in its immunologic characteristics and in its apparent lack of progression over time. Nothing about the immunologic or viral-culture studies performed in these patients or about their family members or blood donors suggests that a transmissible agent causes this condition.

Adult↗
PubMed1992

Ten-year follow-up of HIV-infected homosexual men with lymphadenopathy syndrome: evidence for continuing risk of developing AIDS.

Seventy-five homosexual men with lymphadenopathy syndrome (LAS), subsequently shown to be seropositive for the human immunodeficiency virus (HIV), were enrolled in a prospective study in Atlanta in 1982 and 1983. Subjects have been followed up at 3- to 6-month intervals with clinical and immunologic evaluations, including analysis of T-cell subsets. As of February 28, 1991, AIDS had developed in 36 (48%) of the 75 men. The AIDS cases continued to occur through the 10th year after onset of LAS; the 10-year cumulative incidence of AIDS was 56.6% (Kaplan-Meier survival analysis). Six-year incidence rates following the first observation of a T-helper cell count greater than or equal to 500/mm3, 400-499/mm3, 300-399/mm3, 200-299/mm3, and less than 200/mm3 were 29, 35, 50, 58, and 88%, respectively. Among individual symptoms and signs, only thrush conferred a poorer prognosis (odds ratio = 5.80; 95% confidence interval, 2.93, 11.39, p less than 0.001, Mantel-Byar analysis). The risk of AIDS persists 10 years after the onset of LAS. The AIDS incidence is related directly to T-helper cell depletion; with the exception of thrush, the presence or absence of symptoms and signs appears to be of lesser prognostic significance.

AIDS-Related Complex↗
PubMed1991

Longitudinal evaluation of neuropsychological function in homosexual men with HIV infection: 18-month follow-up.

Subjects were 21 men with persistent generalized lymphadenopathy (PGL, n = 13) or AIDS-related complex (ARC, n = 8), who were not receiving anti-retroviral medication, and 21 controls. At baseline, mild cognitive impairment was detected in language, memory, attention, and visual and auditory processing, primarily in patients with ARC. On follow-up, the ARC group showed continued impairment and abnormalities on new measures of distractibility and activities of daily living. Although mild decline in verbal memory was noted for some patients, overall neuropsychological profiles did not show deterioration. Nomenclature for the pattern of mild, stable neuropsychological changes in patients with cognitive symptoms is discussed. Two interdisciplinary panels have recommended the term HIV-1-associated minor cognitive/motor disorder. Unlike the term AIDS dementia, it does not imply progression or a diagnosis of AIDS.

AIDS Dementia Complex↗
PubMed1991

Individual probability for onset of full-blown disease in patients infected with human immunodeficiency virus type 1.

Increased concentrations of neopterin, a marker for cell-mediated immune activation, and decreased numbers of CD4+ T cells, are predictors for progression of disease after infection with human immunodeficiency virus type 1. Previous studies have demonstrated different rates of onset of full-blown acquired immunodeficiency syndrome (AIDS) for groups of patients, defined by laboratory marker values, who were initially symptom-free. By re-analysis of one such study, we demonstrate how for an individual patient, the individual marker values, together with a prior risk estimate, can be converted into current or accumulated post-test probability of onset of AIDS at a certain time. We used a statistical technique suggested by Albert et al. (Clin Chem 1984;30:69-76), which allows incorporation of fixed and time-dependent covariates. Besides allowing individual projections, the method shows that the predictive abilities of CD4+ T cell numbers and of neopterin concentrations do not vary greatly with regard to time of observation; both laboratory markers independently modulate the underlying prior probability of AIDS onset, which is significantly increased with the passage of time.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Lack of correlation between human herpesvirus-6 infection and the course of human immunodeficiency virus infection.

Human herpesvirus-6 (HHV-6) and human immunodeficiency virus (HIV) are both tropic for CD4+ lymphocytes. To determine whether HHV-6 infection affects the susceptibility to or the course of HIV infection, HHV-6 titers were measured by an anticomplement immunofluorescence assay in serum of three groups of homosexual or bisexual men: (1) those with AIDS (n = 78), (2) those with HIV-associated lymphadenopathy (LAS; n = 81), and (3) those who were HIV-seronegative (n = 55). Early and late serum samples were available for 45 men with LAS (median interval 49 months). Men with early LAS did not differ from HIV-seronegative men in either the percentage that were HHV-6-seropositive or in the distribution of titers. There was a significantly lower percentage of seropositives in AIDS patients than in the other two groups (P less than .01). LAS patients who progressed to AIDS did not differ in percentage seropositivity or distribution of titers from nonprogressors. HHV-6 titers tended to decrease over time. HHV-6 titers late in LAS were similar to those in AIDS patients. These findings suggest that it is unlikely that previous exposure to HHV-6 either predisposes to or affects the course of HIV infection.

AIDS-Related Complex↗
PubMed1989

Human T-cell lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia-lymphoma in a patient infected with human immunodeficiency virus type 1 (HIV-1).

A patient had adult T-cell leukemia-lymphoma in the unusual setting of coinfection with human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus type I (HTLV-I). The leukemic cells were CD4 positive and showed clonal genetic rearrangement of the T-cell receptor complex. Cytogenetic analysis showed three clonal karyotypic abnormalities: trisomy 3 and two translocations [t(1;15), (X;1)]. The patient was seropositive for HIV and HTLV-I; HTLV-I and HIV-1 DNA sequences were detected in peripheral blood leukocytes by the polymerase chain reaction. The HTLV-I sequences were detected in a relatively high proportion of mononuclear cells (at least 1 in 30 cells), whereas HIV-1 sequences were detected in a smaller proportion of cells (at least 1 in 3000 cells). Clinical remission was achieved after chemotherapy. There was a decrease in the proportion of HTLV-I positive mononuclear cells (at least 1 in 1000 cells), whereas the proportion of HIV-1 positive cells was relatively unchanged (at least 1 in 1000 cells). Adult T-cell leukemia-lymphoma in the setting of HIV coinfection may become increasingly common because asymptomatic retroviral coinfections are frequent.

Adult↗
PubMed1989

Deterioration in immunologic status of human immunodeficiency virus (HIV)-infected homosexual men with lymphadenopathy: prognostic implications.

Changes in immunologic parameters were followed in members of a cohort of human immunodeficiency virus (HIV)-positive homosexual or bisexual men with lymphadenopathy and were analyzed for differences between those who have and those who have not progressed to the acquired immunodeficiency syndrome (AIDS) (progressors, nonprogressors). T helpers and the Th/Ts ratio were lower in progressors than in nonprogressors both at entry into the study and at the latest visit. T suppressors were not different in the two groups at entry but were higher in nonprogressors at the latest visit. Evaluation of the patterns of change over time showed that T helpers and Th/Ts ratios tended to decrease over time in both nonprogressors and progressors, while T suppressors increased in nonprogressors and decreased in progressors. Although progressors had a greater deterioration in immunologic parameters over time, nonprogressors also had significant deterioration when compared with controls. Based on the respective percentages of men with abnormal or normal T helpers or Th/Ts ratio at entry who have already progressed to AIDS, we would conservatively estimate, considering their latest T helpers and Th/Ts ratio, that at least an additional 16 (32%) of our nonprogressors will develop AIDS in the next 5 years.

AIDS-Related Complex↗