Human T-lymphotropic virus type III infection in previously immunocompromised hosts.

The human T-lymphotropic virus type III (HTLV-III) is the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). HTLV-III infection in patients with prior underlying immune deficiency states such as cancer has not yet been studied. We report on the occurrence of clinically atypical opportunistic infections in previously immunocompromised patients that resulted from transfusion-acquired HTLV-III infection.

Serological characterization of HTLV-III infection in AIDS and related disorders.

Current efforts to test blood donors and other persons for exposure to the human T cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome (AIDS), are based on the measurement of serum antibodies to viral antigens. We studied presence of serum antibodies to HTLV-III-related antigens from 767 individuals with AIDS or AIDS-related complex (ARC) or asymptomatic persons at risk for AIDS by using ELISA and immunoblot techniques. Of the 280 specimens from AIDS and ARC subjects that were tested, 99% were ELISA reactive and 96% were immunoblot reactive.

A new HTLV-III/LAV protein encoded by a gene found in cytopathic retroviruses.

The DNA of the HTLV-III/LAV group of retroviruses contains certain additional open reading frames that are not found in typical avian or mammalian retroviruses. The role of these sequences in encoding for gene products that may be related to pathogenesis remains to be resolved. An open reading frame whose 5' end overlaps with the pol gene, but is unrelated to the env gene, has been observed in HTLV-III/LAV and visna virus, both cytopathic mammalian retroviruses.

Antibodies to human T-lymphotropic virus type III (HTLV-III) in saliva of acquired immunodeficiency syndrome (AIDS) patients and in persons at risk for AIDS.

Whole saliva samples collected from available people at risk in Boston for infection with human T-lymphotropic virus type III (HTLV-III/LAV), from late 1984 through early 1985, were analyzed for the presence of antibodies to viral proteins. Fourteen of 20 (70%) acquired immunodeficiency syndrome (AIDS) patients and 14 of 15 (93%) AIDS-related complex (ARC) patients had salivary antibodies that reacted with the virus-encoded glycoproteins gp160 and gp120 of HTLV-III infected cells. All of the AIDS and ARC patients had serum antibodies to the same antigens.

Association of human T lymphotropic virus type III antibodies with sexual and other behaviors in a cohort of homosexual men from Boston with and without generalized lymphadenopathy.

Forty asymptomatic homosexually active men seen at a Boston community health center and 39 men with generalized lymphadenopathy were interviewed and filled out detailed epidemiologic questionnaires. Twenty percent of the asymptomatic men and 92 percent of those with lymphadenopathy had antibodies to human T lymphotropic virus type III (HTLV-III). None of the men have subsequently had the acquired immune deficiency syndrome (AIDS).

Pathogenesis of B cell lymphoma in a patient with AIDS.

Lymphoma occurs at increased frequency in patients with the acquired immunodeficiency syndrome (AIDS). We studied, using serologic and molecular techniques, one such lymphoma for (a) evidence of infection with human T lymphotropic virus, type III (HTLV-III), and Epstein-Barr virus (EBV), (b) monoclonal rearrangement of immunoglobulin and T cell receptor genes, and (c) rearrangement of the c-myc oncogene. Immunoglobulin and T cell receptor gene studies demonstrated that the tumor was of monoclonal B cell origin.

Human T-lymphotropic virus type III in high-risk, antibody-negative homosexual men.

A cohort of 215 asymptomatic homosexually active men from a Boston community health center are being prospectively followed to assess the natural history of the human T-lymphotropic virus type III (HTLV-III) infection. To determine if certain asymptomatic persons who are HTLV-III antibody negative may be viremic, an algorithm was developed that defined high-risk characteristics (a sexual partner with the acquired immunodeficiency syndrome [AIDS]; more than 100 homosexual partners; or leukopenia, lymphopenia, neutropenia, or thrombocytopenia). Of 33 asymptomatic homosexual men who did not have antibody to HTLV-III and whose cases have not been previously reported, 2 had HTLV-III recovered from their lymphocytes.

Intra-blood-brain-barrier synthesis of HTLV-III-specific IgG in patients with neurologic symptoms associated with AIDS or AIDS-related complex.

Intra-blood-brain-barrier production of virus-specific antibody is good evidence of infection within the blood-brain barrier. Patients with the acquired immuno-deficiency syndrome (AIDS) have an increased incidence of neurologic abnormalities--i.e.

Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome.

We conducted virus-isolation studies on 56 specimens from the nervous system of 45 patients in order to determine whether human T-cell lymphotropic virus Type III (HTLV-III) is directly involved in the pathogenesis of the neurologic disorders frequently encountered in the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex. We recovered HTLV-III from at least one specimen from 24 of 33 patients with AIDS-related neurologic syndromes. In one patient, HTLV-III was isolated from the cerebrospinal fluid during acute aseptic meningitis associated with HTLV-III seroconversion.

Therapeutic options in hairy-cell leukemia.

Hairy-cell leukemia is a well-characterized, pathologic disorder. The majority of cases are B lymphocyte in origin with circulating hairy cells, splenomegaly, and, not infrequently, pancytopenia included in the clinical findings. Observation, splenectomy, glucocorticoids (ie, for vasculitic manifestations), and alkylating agents are the currently recommended treatment for this disease.

A new HTLV-III/LAV encoded antigen detected by antibodies from AIDS patients.

A newly identified protein from HTLV-III/LAV, the virus implicated as the etiologic agent of the acquired immune deficiency syndrome, was studied. This protein, which has a molecular weight of 27,000 (p27), was shown by amino acid sequencing to have a coding origin 3' to the env gene on the HTLV-III genome. The presence of antibodies to p27 in virus-exposed individuals indicated that this gene is functional in the natural host.

Bacterial expression of the acquired immunodeficiency syndrome retrovirus p24 gag protein and its use as a diagnostic reagent.

A retrovirus [lymphoadenopathy-associated virus, human T-cell leukemia virus type III, acquired immunodeficiency syndrome (AIDS)-related virus] suspected of causing AIDS has been isolated recently. The detection of exposure to this retrovirus in donors of various blood products is important to prevent transmission of the disease from these donors to recipients. In the majority of cases, the detection of antibodies directed against either the viral core protein, a Mr approximately equal to 24,000 protein termed p24 gag, or the viral envelope antigen is proof of previous viral infection.

HTLV-III infection among health care workers. Association with needle-stick injuries.

Health care workers are caring for an increasing number of persons infected with human T-cell lymphotropic virus type III (HTLV-III), the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). We studied 361 health care and clinical laboratory personnel from institutions in several metropolitan areas with both high and moderate levels of HTLV-III infection among high-risk group members to evaluate routes of exposure to and seropositivity for HTLV-III. Protection of the privacy of subjects and prospective determination of risk factors were integral components of the study design.

Aflatoxin metabolism in humans: detection of metabolites and nucleic acid adducts in urine by affinity chromatography.

A high-affinity IgM monoclonal antibody specific for aflatoxins was covalently bound to Sepharose 4B and used as a preparative column to isolate aflatoxin derivatives from the urine of people and experimental animals who had been exposed to the carcinogen environmentally or under laboratory conditions. Aflatoxin levels were quantified by radioimmunoassay and high-performance liquid chromatography after elution from the affinity column. In studies on rats injected with [14C]aflatoxin B1, we identified the major aflatoxin-DNA adduct, 2,3-dihydro-2-(N7-guanyl)-3-hydroxy-aflatoxin B1 (AFB1-N7-Gua), and the oxidative metabolites M1 and P1 as the major aflatoxin species present in the urine.

Antibody seronegative human T-lymphotropic virus type III (HTLV-III)-infected patients with acquired immunodeficiency syndrome or related disorders.

The human T-lymphotropic virus type III (HTLV-III) is the primary cause of the acquired immunodeficiency syndrome (AIDS) and related disorders (ARC). Prior studies have reported that nearly all symptomatic patients with AIDS or ARC manifest antibody to HTLV-III. This observation has engendered efforts to screen for HTLV-III, especially prior to blood donation, with assays for antibody to HTLV-III.

Clinical spectrum of HTLV-III in humans.

We have studied the clinical and laboratory manifestations of infection with human T-cell lymphotropic virus type III in various epidemiological cohorts. The spectrum of infection ranges from an asymptomatic but apparently contagious carrier state to severe immunodeficiency with opportunistic infections and neoplasms. Study of virus structure-function relationships and host response to viral infection in hosts with different clinical manifestations should provide strategies for therapeutics and vaccine development as well as enhance our understanding of the biology of human retroviruses.

Virus envelope protein of HTLV-III represents major target antigen for antibodies in AIDS patients.

In this study, two glycoproteins (gp160 and gp120) that are encoded by human T-cell lymphoma virus type III (HTLV-III) were the antigens most consistently recognized by antibodies found in patients with the acquired immune deficiency syndrome (AIDS) and with the AIDS-related complex (ARC) and in healthy homosexual males. The techniques used to detect the glycoproteins were radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (RIP/SDS-PAGE). Although most antibody-positive samples from ARC patients and from healthy homosexual males also reacted with the virus core protein p24, less than half of the AIDS patients revealed a positive band with p24 under the same conditions.

Modification of aflatoxin B1 binding to DNA in vivo in rats fed phenolic antioxidants, ethoxyquin and a dithiothione.

The effects of dietary administration of 3,5-di-tert-butyl-4-hydroxytoluene (BHT), 2(3)-tert-butyl-4-hydroxyanisole (BHA), ethoxyquin (EQ) and 5-(2-pyrizinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) on aflatoxin B1 (AFB1) - DNA adduct formation in vivo in livers and kidneys of rats were investigated. Male F344 rats were treated with 1 mg/kg AFB1 by i.p.

Substrate specificity of human liver cytochrome P-450 debrisoquine 4-hydroxylase probed using immunochemical inhibition and chemical modeling.

A significant population of humans (5 to 10%) are phenotypic poor metabolizers of debrisoquine. We have isolated the cytochrome P-450 isozyme from rat liver responsible for this activity and have shown that antibodies raised against the protein are able to inhibit this catalytic activity in human liver microsomes (Distlerath, L. M.

Seroepidemiology of human T-lymphotropic virus type III among homosexual men with the acquired immunodeficiency syndrome or generalized lymphadenopathy and among asymptomatic controls in Boston.

We studied a cohort of 45 homosexual men with the acquired immunodeficiency syndrome, 78 with persistent unexplained generalized lymphadenopathy, and 160 asymptomatic homosexual controls for serologic evidence of infection with human T-lymphotropic virus type III (HTLV-III). Study participants were recruited from a community-based health center and a university hospital practice. Ninety-eight percent of men with the syndrome and greater than 90% of men with generalized lymphadenopathy had antibody to HTLV-III, while 21% of the controls were positive (p less than 0.

Isolation and functional analysis of human B cell populations. I. Characterization of the B1+B2+ and B1+B2- subsets.

Distinct populations of human B lymphocytes can be identified by their expression and/or co-expression of the B cell-restricted antigens B1 and B2. Dual fluorochrome staining and flow cytometric cell sorting permitted the isolation of the B1+B2+ and B1+B2- cells to homogeneity. In contrast, very few B1-B2+ cells were obtainable from normal lymphoid organs.