Fear of AIDS. A communication from biologists to psychologists/sociologists.
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Biomedical subjects
Publications and source records attributed to P Ebbesen.
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The long-term effects of seropositivity for human T-lymphotropic virus type III (HTLV-III) on T-lymphocyte subsets and health status were evaluated in longitudinal studies of 250 initially healthy homosexual men. The relative risk of having an inverted T-lymphocyte helper-to-suppressor ratio rose from 14.3-fold among short-term seropositive subjects (less than 19 months) to 46.9-fold among long-term seropositive subjects (greater than 29 months) in comparison with the risk among seronegative subjects. Overall, 91.7% of long-term seropositive men had inverted ratios, compared with 12.9% of seronegative men. None of the seropositive men who developed an inverted ratio later reestablished a normal ratio. Both decreased T-helper cell number and percentage (p = 0.003) and increased T-suppressor cell number and percentage (p = 0.03) were significantly correlated with duration of seropositivity. Among seropositive persons, lymphadenopathy was a highly significant short-term as well as long-term consequence, whereas diarrhea, oral thrush, and herpes zoster were correlated with long-term seropositivity. Overall, 50% of long-term seropositive men compared with 16% of seronegative men developed at least one of five clinical symptoms (p less than 0.003). We conclude that a high proportion of persons infected with HTLV-III will develop measurable immunologic and clinical abnormalities.
Serum samples from 40 Danish patients with familial polyposis coli and 105 normal blood donors were typed for eight Gm and one Km markers. The distribution of all Gm phenotypes as a group was significantly different in the patient population as compared to the controls. Examination of individual Gm phenotypes showed an increased frequency of Gm3;5,13 in the patients.
Recent changes in sexual habits have likely contributed to the emergence of a new sexually transmissible agent, acquired immune deficiency syndrome (AIDS) virus. This virus may have been present in central Africa as early as 1959; however, frequent infection did not produce an epidemic until the late 1970's. Migration of Africans from rural to urban areas may have contributed to the transmission of AIDS virus. An estimated 1.7 million Americans and 5,000,000 Africans are infected. An incubation period of five years +/- 36 months to onset of disease is estimated. Development of AIDS during a three-year period after detection of AIDS virus antibodies has occurred in 30% of homosexual males in Manhattan and 10% of infected men in Denmark. Conservatively, in excess of 20% of seropositive will likely develop AIDS. Although modification of sexual behavior is recommended, those who will develop AIDS in the near future are already infected. Public health workers ought to be preparing for additional pandemics of infectious diseases which may arise from changing cultural habits.
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Trichosporon beigelii was isolated from the anal region in 45 (13%) of 343 Danish homosexual men. T. beigelii was also present on the scrotal skin of six anal carriers who were accessible for re-examination, and white piedra of the genital hair was observed in two cases. Because T. beigelii may cause systemic infections in compromised hosts it may pose a threat to homosexuals infected by HTLVIII/LAV virus.
Sera of native inhabitants of Arctic regions were assayed for antibodies to HTLV-I by the ELISA technique followed by competition experiments to confirm antibody specificity. Residents of 7 widely separated Alaskan villages exhibited prevalence rates of 0 to 12% for HTLV-I antibodies. Less than 1% of Greenland Eskimos were HTLV-I antibody-positive. Residents of 3 northern Swedish regions ranged in HTLV-I antibody prevalence from 0 to 5%. Sera of healthy native inhabitants of Alaska and northern Sweden were similarly assayed for antibodies to HTLV-II. No additional sera were shown to be positive for HTLV-II antibodies. While some of the HTLV-I antibody-positive sera exhibited cross-reactivity with HTLV-II antigens, competition experiments using disrupted HTLV-II or purified HTLV-I p24 as test antigens indicated that the primary antibody response in all cases tested was elicited by HTLV-I. Our results show that HTLV-I distribution is not restricted to endemic areas in warm, humid climates, but extends to Arctic regions. Within these regions, HTLV-I exhibits the same restricted distribution seen in other areas where virus infection is prevalent. The Arctic does not seem to be a reservoir for HTLV-II infection. The origin of HTLV-I in Arctic areas is not known. One may speculate that foreign visitors introduced the virus into Aleut and Lapp populations, and that it has been maintained there and restricted in its distribution as a result of close familial relationships.
Western blot analysis was used to document the development and changes in human T lymphotropic virus III (HTLV-III) antibody among Danish homosexual men followed longitudinally over three years. Reactivity against p15, p24, and p55 appeared earliest. After seroconversion the antibody concentration fluctuated, but in one instance a steady decline in banding intensity was seen during the 18 months before onset of the acquired immune deficiency syndrome (AIDS) and throughout the remaining eight months of his life.
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Female hairless inbred hr/hr mice were exposed to UV-B irradiation from Philips TL 40W/12 fluorescent tubes. Fractionated irradiation, given as single daily doses 5 days a week, was gradually increased from 0.04 to 0.4 J/cm2 over 2 weeks. Irradiation at 0.4 J/cm2 was continued for 20 weeks. Selenium supplementation given as sodium selenite in the drinking water at 2, 4 and 8 mg/l began 3 weeks before UV-irradiation and continued thereafter. Development of skin tumors was followed by weekly examinations. Statistical analyses revealed significant dose-dependent selenium-mediated protection against UV-light-induced skin cancer. Leukemia developed in 5 of 150 UV-irradiated mice as opposed to none in a group of 60 unirradiated mice.
A series of derivatives of 5-(aminomethyl)-8-methoxypsoralens, 8-[(3-aminopropyl)oxy]psoralens, and 5-[[[3-(tri-methylammonio)propyl]methyl]-8-methoxypsoralen has been synthesized and their potential as PUVA reagents examined. While the DNA association constants of selected psoralens were found to be 10(5)-10(6)L mol-1, corresponding to efficient binding, flow linear dichroism studies indicated that only the 8-substituted psoralens bind to DNA by intercalation. Furthermore, the ability to photoinduce interstrand cross-links in calf thymus DNA, in vitro, was as efficient as that of 8-methoxypsoralen for the 8-substituted psoralens, which were up to 25 times as efficient as the 5-substituted psoralens. Four of the psoralens studied were radiolabeled and used to study photobinding to DNA. Analogously to the cross-binding results, the 8-substituted psoralens were more efficiently photobound than the 5-substituted, while only slight differences were found in the photobinding-cross-linking ratio. The photoreactivity of the aminopsoralens toward cyclohexene and 2'-deoxythymidine was enhanced compared to that of 8-methoxypsoralen, the effect being most pronounced when the amino group is close to the furocoumarin ring system. Most of the new compounds were less photocytotoxic than 8-methoxypsoralen to NHIK 3025 cells, in vitro, and they caused less light-induced DNA interstrand cross-linking, in situ, in these cells. A clear correlation between the photocytotoxicity and the DNA cross-linking ability of the psoralens was observed. Several of the derivatives showed more pronounced effects in the light-dependent skin thickening (inflammatory) test on mice than 8-methoxypsoralen. No correlation between DNA cross-linking capacity, in vitro, and skin phototoxicity was found for this series of psoralens.
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In a comparative study of populations at high and low risk of nasopharyngeal carcinoma (NPC), sera from 442 Eskimo and 770 Danish children and adolescents were tested for the presence of antibodies against Epstein-Barr virus (EBV). Eskimo children in Greenland were seropositive at an early age and showed significantly higher titers of IgG antibody to the viral capsid antigen (VCA) (p less than 0.0001) and soluble (S) antigen (p less than 0.005) than Danes matched for age and sex, but had similar levels of IgA antibody to VCA and IgG antibody to the early antigen (EA). The high geometric mean VCA (IgG) titers found in certain age groups of Eskimo children were as high as those previously reported from areas in Africa highly endemic for Burkitt's lymphoma. In Greenland, neither location nor household size was a determining factor for prevalence or titer of VCA (IgG). The high antibody titers among Eskimo children probably reflect exposure to a large inoculum of EBV at the time of primary infection, infection early in life and/or re-exposure due to the higher incidence of EBV infection in Greenland. In view of the high incidence of NPC in Greenland and the known association of this tumor with EBV, we speculate that the time and quantitative aspects of the primary infection are also factors of relevance in the etiology of NPC.
Sera taken from 250 Danish homosexual men in December 1981 as part of a prospective study of the acquired immunodeficiency syndrome (AIDS) were examined for the presence of HTLV-III antibody with an enzyme-linked immunosorbent assay. Antibody was present in 22 (8.8%) of the men. Seropositivity was most strongly associated with sexual exposure to men in the United States (relative risk 3.5; p less than 0.007). Increased frequency of anal receptive intercourse was also independently associated with seropositivity (p less than 0.05), but age, years of homosexual experience, number of homosexual partners, and use of nitrite inhalant were not independent risk factors. The frequency of seroconversion from absence to presence of HTLV-III antibody appeared to be about 1% a month in this community during December 1981 to February 1983. Of the 22 men who were originally seropositive, two (9%) subsequently developed AIDS as defined by the Centre for Disease Control and two (9%) others the AIDS related complex. Blood was taken in addition from two of the men to develop AIDS earliest in Denmark (diagnosed 1981) at the same time as the initial survey in 1981; both were seropositive. The spread of HTLV-III from high to low risk areas and the subsequent appearance of illnesses related to AIDS in the seropositive group support the hypothesis that HTLV-III is causally related to the development of AIDS.
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To investigate risk factors for immunologic abnormalities among homosexual men, T-lymphocyte helper/suppressor (OKT4/OKT8) ratios were determined in 78 healthy Danish homosexual men. Ratios in 26 men (33%) were low (less than 1.00). Visiting the United States in 1980 to 1981 was a strong (7.7-fold) risk factor for having a ratio less than 1.00. Among nine travelers who visited only once, the risk of having a low ratio increased significantly if the visit had occurred in 1981. A risk of similar magnitude (6.9-fold) was found among the three men who had not been to the United States but who reported homosexual contact with a Danish man who became ill with Kaposi's sarcoma. Risk of low ratios did not correlate with age or years of homosexual activity. Promiscuity was not a significant risk factor, but these men generally had fewer sex partners than that which has been reported from the United States. Neither nitrite inhalant use nor cytomegalovirus antibody (prevalence or titer) was associated with low ratios. These data support the hypothesis that a transmissible biologic agent may be etiologically responsible for the low helper/suppressor ratios in homosexual men.
Interviewed to obtain the first quantitative data from Scandinavia on lifestyle factors of possible importance for their health were 259 Danish male homosexuals. The frequency of various sex acts, frequency of change in partner, visits to the United States, sexual contacts with victims of the immune suppression syndrome, education, smoking and drug habits, and recent medical problems were recorded. Of those interviewed, 170 were from the Danish capital, Copenhagen, and 89 were from a smaller provincial town, Aarhus. Sexual habits and most other factors were very similar in men from the two cities. Furthermore, the sex habits of those who had visited a venereal disease clinic were similar to those of the group as a whole except for a frequent change of partners. Our data on level of sexual activity resemble those available for the San Francisco Bay area of 1970. The Copenhagen men, however, had more partners per year, had more sexual contact with U.S. citizens and immune suppression syndrome victims, and more had used nitrite inhalation than the men in Aarhus. The frequency of venereal disease was the same in the two groups, but the Danish cases of Kaposi's sarcoma and the acquired immune deficiency syndrome all have come from the Copenhagen area. Two of those interviewed have developed AIDS subsequent to homosexual contact with a case of Kaposi's sarcoma.