Transmission of human immunodeficiency virus by transplantation of a renal allograft, with development of the acquired immunodeficiency syndrome.
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Biomedical subjects
Publications and source records attributed to W C Saxinger.
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Serum IgD levels in individuals infected with the human immunodeficiency viruses (HIV) were studied as a means of monitoring the character and timing of B cell activation in individuals with this infection. Significantly increased levels of IgD were characteristic of homosexual men who were HIV seropositive but asymptomatic or mildly symptomatic. The hyper IgD globulinaemia became progressively more pronounced in patients with increasingly severe infection and reached its most marked level in patients with AIDS-related complex (ARC). In ARC patients, IgD levels were increased 8.8-fold above normal which was disproportionately greater than the 2.4-fold increase in IgG, the 1.8-fold increase in IgA and the 1.6-fold increase in IgM. IgD levels declined in AIDS patients (although remained elevated compared to controls). The data suggest that an unusual type of B cell activation is responsible for the unique pattern of hypergammaglobulinaemia seen in this disease and that the B cell activation occurs early in the pathogenesis of HIV infection, often before development of symptoms, and continues throughout the course of infection.
Serum samples from feral populations of African green monkeys (Cercopithecus aethiops) were screened for antibodies to the simian T-lymphotropic virus, type I (STLV-I). Blood samples had been collected from 336 monkeys in 4 regions of central and southern Kenya in 1978 and 1979, from 114 monkeys in central Ethiopia in 1973, and from 85 monkeys from the Kampala region of Uganda in 1966. A total of 178/535 monkeys (33%) were seropositive (STLV-I+). Only 4/114 monkeys (4%) from Ethiopia were seropositive compared to 25/85 Ugandan monkeys (29%) and 149/336 Kenyan monkeys (44%). Epidemiological analysis of the Kenyan monkeys showed that 37% of the males and 54% of the females were STLV-I+, and that there was a progressive increase in the proportion of STLV-I+ monkeys of both sexes with age, rising from an average of 16% in infants (less than 9 months) to an average of 69% in adults (greater than 42 months). The proportion of STLV-I+ monkeys was higher among females in each age category. Seropositivity for antibodies to STLV-I had no apparent effect on the health of monkeys, and no association with the occurrence of Hepatocystis parasitemia was seen in this species. The analysis of data from infants of STLV-I+ mothers showed that seroconversion had occurred in 1 of 3 cases, suggesting that vertical transmission of the STLV-I virus is not an inevitable consequence for infants of seropositive mothers.
We examined the usefulness of a counterimmunoelectrophoresis (CIE) technique for detecting antibodies to HTLV-III using sera that previously had been assessed for antibodies to HTLV-III by the standard enzyme-linked immunosorbent assay (ELISA). We selected a subset of 53 sera from patients with the acquired immune deficiency syndrome (AIDS) or the generalized lymphadenopathy syndrome (GLS) in which 81.1% were initially ELISA-positive, and 96.2% were positive by Western blot technique. In our standard HTLV-III CIE technique, 58.5% were positive and repeat testing increased the yield to 67.9%. Varying several parameters of the standard CIE assay did not improve sensitivity. We also studied 20 ELISA-negative and 10 ELISA-borderline sera from normal controls; all were negative by CIE. These results indicate that CIE may be used for detection of human serum antibodies to HTLV-III, but that the present assay was less sensitive than the HTLV-III ELISA.
We studied 56 asymptomatic homosexual male volunteers in Pittsburgh for 1 1/2 yr for relationships between cytomegalovirus (CMV) and human T-lymphotropic virus type III (HTLV-III) infections. CMV was most frequently isolated from semen (8%) as compared with throat washings (5.9%) and urine (0%) on initial testing of CMV-seropositive subjects. Other viruses commonly isolated from immunosuppressed patients (herpes simplex virus, adenovirus) were rarely detected in this cohort. Seropositivity to HTLV-III was significantly associated with isolation of CMV from semen in our asymptomatic cohort (odds ratio = 9.5, p = .008). These results suggest that HTLV-III infection is associated with selective, temporal activation of CMV in the genital tract of asymptomatic homosexual men.
Homosexual men were studied for associations among human T-lymphotropic virus type III (HTLV-III) infection, Epstein-Barr virus (EBV) infection, and T cell abnormalities. The presence of IgG antibody to EBV capsid antigen and antibody to EBV early antigen was significantly associated with augmented counts of suppressor T cells in healthy HTLV-III-seronegative men. HTLV-III-seropositive asymptomatic subjects had significantly enhanced titers of antibody to EBV and lower ratios of helper to suppressor T cells compared with HTLV-III-seronegative homosexual men. Of three men who seroconverted to HTLV-III, two had a greater than fourfold increase in titer of IgG antibody to EBV capsid antigen after seroconversion. These results suggest that the interaction of HTLV-III and EBV and their immunologic perturbations are significant in the natural history of this retrovirus infection in homosexual men.
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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. Six (26%) of 23 health care workers with recognized risk factors for AIDS had HTLV-III antibodies. Thirty-nine (14%) of 278 workers at one institution as well as a total of five workers from other institutions reported possible percutaneous exposure to HTLV-III, usually injuries with needles that had been used on AIDS patients. There were three HTLV-III seropositive subjects who reported possible parenteral exposure to HTLV-III but no recognized AIDS risk factors. One was a symptomatic female, subject A, and her apparent sources of HTLV-III exposure were two puncture wounds, without injection of blood, made with needles used on AIDS patients. Human T-cell lymphotropic virus type III was cultured from her asymptomatic, seronegative long-term sexual partner, apparently representing female-to-male transmission. For the two other seropositive workers (subjects B and C) with nosocomial parenteral exposure, we could not rule out heterosexual transmission as a possible source of HTLV-III exposure. These latter two cases as well as the identification of seropositive health care providers from known risk groups point to the need for thorough case investigation to identify routes of exposure in health care workers. The risk of nosocomial HTLV-III transmission appears to be low and related to percutaneous exposure. Medical personnel should be trained systematically in the proper techniques and handling of instruments for phlebotomy and similar procedures to decrease occupational exposure to HTLV-III.
Fifty of 75 serum samples collected in the West Nile district of Uganda between August 1972 and July 1973 contained antibodies reactive with human T-cell leukemia (lymphotropic) virus type 3 (HTLV-III; mean titer, 601), while 12 of 75 samples were positive in a similar test for HTLV type 1 (HTLV-1) antibodies (mean titer, 236). The samples were screened by enzyme-linked immunosorbent assay and positive results were confirmed by a newly developed unlabeled antibody-peroxidase procedure with enhanced sensitivity for detection of antibody binding to immunoblots of HTLV-III antigen, demonstrating antibodies to proteins with molecular weights of 24,000, 41,000, and 76,000 in nearly all positive samples. Analysis of titration data indicated enhanced titers of antibody against HTLV-III and HTLV-I when coinfection occurred. The high prevalence and relatively low titers [compared to serum from patients with acquired immune deficiency syndrome (AIDS)] of antibodies recognizing HTLV-III proteins in sera from this population at a time that may predate or coincide with the appearance or spread of the AIDS agent (HTLV-III) suggest that the virus detected may have been a predecessor of HTLV-III or is HTLV-III itself but existing in a population acclimated to its presence. It further suggests an African origin of HTLV-III.
10 of 68 CTCL (cutaneous T-cell lymphoma) patients without features of ATLL had antibodies against HTLV-I (human T-cell leukaemia virus, type I). The titre of antibody in these positive patients was generally much lower than that seen in cases of ATLL (adult T-cell leukaemia/lymphoma); geometric mean of 80 for CTCL vs. 8000 for Caribbean ATLL. The presence of HTLV-I antibody was unrelated to clinical remission, relapse, or stages of the disease, and some positives were detected in the earliest phases of mycosis fungoides. Among controls and normal donors between the ages of 40 and 65, only 1 of 36 and 3 of 113, respectively, had low titre antibodies to HTLV-I in their sera. Only 5 of 354 Danish normal donors of all ages had antibody, which was identical to the rate in over 2000 US normal donors. In negative control experiments, these antibodies were unreactive with bovine leukaemia virus. These data suggest that HTLV-I or a related retrovirus crossreactive with HTLV-I occurs in a low percentage of the Danish population and patients with CTCL have such antibodies at an increased rate, but less than the rate seen for ATLL (greater than 90%).
Sera from 119 patients attending a venereal disease clinic in Copenhagen during May 1983 were screened for antibodies to the newly characterized and isolated retrovirus HTLV-III. Ten out of 45 (22%) homosexual patients and two out of 74 (2.7%) heterosexual patients were found to have antibodies against HTLV-III. The homosexual group (except one case that developed AIDS and died during one year observation period) contained otherwise healthy men some of which had no contact with individuals from high-risk areas and only a few sexual partners. These results strongly suggest that Danish homosexuals with only few contacts are also at risk and that sero-epidemiological studies should also include the healthy homosexual group and probably the heterosexual group attending venereal disease clinics.
Two of three chimpanzees given plasma from patients with acquired immune deficiency syndrome (AIDS) or pre-AIDS showed serum antibodies to type III human T-cell leukemia virus (HTLV-III) 10 to 12 weeks after transfusion. One animal also developed lymphadenopathy, transient depression of the ratio of T4 to T8 lymphocytes, and impaired blastogenic responses. No opportunistic infections occurred. Adenopathy persisted for 32 weeks, and antibody to HTLV-III persisted for at least 48 weeks. This transmission of HTLV-III by lymphocyte-poor plasma confirms the potential risk of such plasma or plasma derivatives to recipients. The susceptibility of the chimpanzee to HTLV-III infection and the ability to simulate the human lymphadenopathy syndrome in this animal makes it a valuable model for further study of AIDS.
Embryonal carcinoma (EC) cell lines established from human testicular germ-cell tumours produce, at low frequency, virions morphologically identical to type C retroviruses that have been observed by other workers in human placental tissues. The virus particles are formed while budding from the cell surface, and their numbers are increased by inducing the EC cells with 5-iodo-2'-deoxyuridine and dexamethasone. Assays for RNA-dependent DNA polymerase (reverse transcriptase) associated with purified virions suggested a low level of activity. In addition, another type of virus is occasionally produced by induced cells of three EC lines. These particles also form during the process of budding from the cell surface, but they have surface projections (spikes). Extracellular spiked virions frequently are pleomorphic, with a condensed, eccentric nucleoid, and thus morphologically resemble type B retroviruses. No virions of either type were detected with or without induction in cultures of differentiated EC cells or in cultures of yolk sac carcinoma or teratoma cells, both of which are considered malignant but differentiated derivatives of EC cells. The lack of virion production by these differentiated cells suggests developmental regulation of virus replication.
Cutaneous T-cell lymphomas (CTCL) are neoplasias of mature T-cells and comprise Sezary syndrome, mycosis fungoides and some cases of lymphomatoid papulosis. Clinically this group of disorders differ from the more aggressive neoplasias of mature T-cells known as adult T-cell leukemia/lymphoma and T-cell lymphosarcoma leukemia which are associated with human T-cell leukemia virus (HTLV). We have found that of 68 patients from Denmark with CTCL ten were positive for HTLV antibodies and that the neoplastic T-cells from skin specimens in seven of eight HTLV-antibody positive patients studied by DNA flow cytometry exhibit DNA aneuploidy. Either one or two hyperdiploid cell clones were present. Aneuploidy was found in two patients with histologically verified mycosis fungoides, in four patients with histological non-diagnostic mycosis fungoides, and in one patient with lymphomatoid papulosis. The present data indicate that further seroepidemiologic survey studies of cutaneous T-cell lymphomas should include the early histological non-diagnostic stages, especially when aneuploidy is present.
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