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Biomedical subjects

I H Frazer

Publications and source records attributed to I H Frazer.

At least 91 records · Page 5Linked to original sources

Immunology of anogenital human papillomavirus (HPV) infection.

A subgroup of human papillomaviruses (HPVs) is implicated in the aetiology of neoplastic change in anogenital epithelium. Although abundant circumstantial evidence exists for the involvement of the immune system in the control of HPV infection, restriction of infection to epithelium and the lack of a viral productive phase pose problems for immune response induction, and for immunological effector mechanisms. In this article we discuss how HPV antigens may be presented to the immune system on the surface of keratinocytes as well as, or in addition to, presentation by 'classical' antigen presenting cells, and outline putative roles for non-specific and specific (B- and T-cell) effector functions. We discuss the prospects for a vaccine and the use of anti-HPV antibodies in immunodiagnosis.

Antigen-Presenting Cells↗

Male partners of women with genital human papillomavirus infection. An assessment of colposcopic abnormalities by histological examination and human papillomavirus hybridization.

Men whose female sexual partners showed histological evidence of human papillomavirus infection were examined. Human papillomavirus DNA was identified in 29 of 35 biopsy samples of colposcopically-identified penile lesions. Human papillomavirus strains that were related to human papillomavirus genotypes 6/11 were observed most commonly (seven of eight patients) in the partners of patients with warty atypia or condylomata, while human papillomavirus strains that were related to human papillomavirus genotypes 16/18 were most-commonly (eight of 15 patients) observed in tissue from the partners of patients with cervical intraepithelial neoplasia. Measurement of human papillomavirus DNA in lesions by the filter in-situ hybridization technique more-frequently indicated human papillomavirus infection (29 of 35 lesions) than did conventional histopathological assessment (21 of 35 lesions) in this "high-risk" group. We conclude that colposcopically-identifiable lesions in male sexual partners are likely to contain human papillomavirus DNA, even if is no definite histological evidence of human papillomavirus infection is present, and that such lesions frequently contain strains of human papillomavirus that have been associated with the development of anogenital carcinoma.

Colposcopy↗

Cerebral dysfunction with evidence of cerebral HIV infection amongst asymptomatic HIV seropositive subjects.

Twelve asymptomatic HIV seropositive subjects ages 21 to 40 years were examined for serologic evidence of cerebral HIV infection, for cerebral structural abnormalities, and for neuropsychologic evidence of cerebral dysfunction using standard methods. Eleven of the 12 had antibody to HIV in the cerebrospinal fluid (CSF). Nine subjects had oligoclonal immunoglobulins in the CSF, of whom five had some for which there were no corresponding serum oligoclonal immunoglobulins ('unique' oligoclonal immunoglobulins). Intracerebral synthesis of HIV specific antibodies was demonstrated for four subjects. Significant deficits of memory and frontal lobe function were found in five of the 12 subjects. Subjects who had oligoclonal immunoglobulins unique to the CSF all had significant neuropsychological abnormalities. No structural cerebral abnormalities were demonstrated using CT scanning for any subject tested. These results support other evidence that HIV is neurotropic and capable of directly inducing brain damage even in immunologically normal subjects. Tests of memory and frontal lobe function are frequently abnormal in patients with early HIV infection, and identify as abnormal a similar group of patients to immunological or biochemical tests which might indicate cerebral HIV infection.

Acquired Immunodeficiency Syndrome↗

Depressed activities of purine enzymes in lymphocytes of patients infected with human immunodeficiency virus.

Enzyme activities were studied in peripheral blood lymphocytes from patients infected with, or at risk for, infection with human immunodeficiency virus (HIV). No significant differences were observed in the HIV-infected and HIV-seronegative high-risk patients with regard to enzyme activities of hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) and purine nucleoside phosphorylase (EC 2.4.2.1) in peripheral blood. Adenosine deaminase (EC 3.5.4.4) was significantly (P less than 0.02) depressed in asymptomatic HIV-seropositive patients and HIV-seronegative patients at high risk of HIV infection as compared with a healthy HIV-seronegative population. Adenosine kinase (AK, EC 2.7.1.20) was significantly increased in the asymptomatic seropositive (P less than 0.02) and also in the HIV-seronegative high-risk groups (P = 0.01) compared with the normal controls. AK activity was significantly lower in subjects with AIDS than in the asymptomatic (P less than 0.002) and high-risk groups (P less than 0.01). Taken together, these results indicate that adenosine deaminase and AK activities are influenced by the health of the patient, and that measurement of AK activity may prove useful in monitoring the clinical progress of patients with HIV infection.

Acquired Immunodeficiency Syndrome↗

Influence of human immunodeficiency virus antibody testing on sexual behaviour in a "high-risk" population from a "low-risk" city.

A survey was undertaken of homosexual and bisexual men in Brisbane to establish whether knowledge of their human immunodeficiency virus (HIV)-antibody status had influenced any sexual behaviour that was likely to spread HIV type 1 (HIV-1). Of the 318 respondents, 123 respondents knew their HIV serological status, and 13 of these were HIV seropositive. Of the 195 respondents who previously had not been tested, 10 individuals proved to be HIV seropositive. Eighty-two per cent of subjects stated that they had reduced their sexual activity because of their awareness of the acquired immunodeficiency syndrome (AIDS); this reduction was equally common among those who had or had not previously had their HIV serological status checked. Anal intercourse was practised most frequently by those subjects who were HIV seropositive and were not aware of it; nevertheless, unprotected anal intercourse was common among subjects who knew their HIV serological status, including those who knew that they were HIV seropositive. Eighty-nine of 208 subjects who were practising anal intercourse had never used a condom. Usage of a condom was marginally more common among those subjects who previously had been tested for the presence of HIV antibodies (P = 0.06), and this was particularly so for those subjects who knew that they were HIV seropositive (P less than 0.01). Condom usage was no more common among those subjects who knew that they were HIV seronegative, when compared with those subjects who did not know their status. These data show that knowledge of a negative HIV-antibody test-result has no substantial association with safer sexual behaviour and suggest that whereas targeted information programmes have had some impact on behaviour in high-risk groups in Brisbane, by the end of July 1986, these programmes had not yet resulted in safer sexual practices by the majority of homosexual and bisexual men.

AIDS Serodiagnosis↗

Human papillomavirus--a study of male sexual partners.

Male sexual partners of a cohort of women with genital-tract abnormalities which were associated with human papillomavirus infection were examined for evidence of infection with human papillomavirus. Of the 214 male partners who were examined, 93.5% had visible genital lesions. Of the 196 lesions that were biopsied, 72.5% showed histological evidence of infection with human papillomavirus, and only 20.4% of subjects with histological evidence of human papillomavirus were aware of a lesion. An unexpectedly high proportion (6.1%) of lesions on which a biopsy was performed, particularly those with flat, red, indurated morphology, also showed histological evidence of penile intraepithelial neoplasia. This was not significantly more common among the partners of the women with cervical intraepithelial neoplasia than it was among the partners of the women with other evidence of genital human papillomavirus infection. Penile intraepithelial neoplasia was significantly (P less than 0.001) more common among subjects with no history of non-genital warts. We conclude that the male partners of women with human papillomavirus-associated lesions are very likely to be infected with human papillomavirus, and thus may act as a significant reservoir for the reinfection of their female partners. As the awareness of human papillomavirus-associated lesions was low among the male partners, colposcopic examination and treatment of their male partners, and/or barrier contraception, may be a necessary part of the management of women who are undergoing treatment for human papillomavirus-associated genital disease.

Adult↗

Some adverse reactions to allopurinol may be mediated by lymphocyte reactivity to oxypurinol.

Six of 9 patients with previously documented adverse reactions to allopurinol exhibited transformation of their peripheral blood lymphocytes when these were exposed in vitro to the allopurinol metabolite, oxypurinol. In 2 of these subjects, intradermal skin challenge was positive at 48 hours with either allopurinol or oxypurinol. The evidence presented suggests that some adverse reactions to allopurinol represent delayed-type hypersensitivity to oxypurinol.

Allopurinol↗

Intramuscular versus low-dose intradermal hepatitis B vaccine. Assessment by humoral and cellular immune response to hepatitis B surface antigen.

The capacity of hepatitis B surface antigen (HBsAg) vaccine (which was administered by the conventional intramuscular route or as a one-tenth dose by the intradermal route) to elicit an antibody or delayed-type hypersensitivity response to HBsAg was compared for 40 paired healthy subjects, 20 per group, of whom 38 completed the vaccination protocol. The 40 subjects were allocated at random to receive three doses of 20 micrograms of vaccine intramuscularly, or three doses of 2 micrograms of vaccine intradermally. Titres of antibody to HBsAg (anti-HBs) were expressed in a radioimmunoassay by sample ratio (signal-to-noise) units (SRU). The maximal mean levels of anti-HBs (maximal one month after the third injection) were 108 SRU for the intramuscular group and 51 SRU for the intradermal group, and the levels for the intramuscular group were significantly higher at all other time-points. The levels of anti-HBs declined equally with time over 18 months in both groups. More subjects in the intramuscular group (17 of 19 subjects) showed a response to anti-HBs than in the intradermal group (14 of 19 subjects). Non-respondents in either group responded with similar frequency to further intramuscularly-administered vaccine. The frequency of delayed-type hypersensitivity to HBsAg was similar for both groups. Thus, immunization with HBsAg, when administered intradermally in a dose that is one-tenth of that recommended for intramuscular administration, induces an immune response in healthy subjects. However, since the level of antibody is lower than that after intramuscular injection, revaccination might be needed at more frequent intervals.

Adult↗

Association between anorectal dysplasia, human papillomavirus, and human immunodeficiency virus infection in homosexual men.

Cells from the anorectal mucosa of 61 homosexual men were examined microscopically for evidence of papillomavirus infection and dysplastic changes. There was cytological evidence of dysplasia with concomitant features of human papillomavirus (HPV) infection on at least one occasion in 24 men and of papillomavirus infection without dysplasia on at least one occasion in a further 26: dysplasia was present for over one year in 9 of 14 men who were re-examined. Dysplasia was associated with a history of anal warts, frequent receptive anal intercourse, presence of serum antibody to human immunodeficiency virus (HIV), and immune dysfunction as judged by a low CD4/CD8 ratio, but not with the lifetime number of sexual partners. The association of longlasting dysplasia with anti-HIV was independent of the association with immune dysfunction. Thus infection of anorectal mucosal cells with papillomavirus seems to be frequent among homosexual men and may predispose to dysplasia.

Acquired Immunodeficiency Syndrome↗

'Acute' autoimmune hepatitis.

A previously well young woman presented with an acute hepatitis resembling viral hepatitis and a liver biopsy after 5 weeks showed features of acute hepatitis. Infection with identifiable viruses or other organisms known to cause hepatitis was excluded. Evidence for autoimmune chronic active hepatitis ab initio included prolonged fever, lymphadenopathy, urticaria, arthralgia, Coombs' positive hemolytic anemia, lymphopenia, a markedly raised level of immunoglobulin G and a positive antinuclear antibody test. Liver biopsies after 4 and 28 months showed typical histologic features of autoimmune chronic active hepatitis and the subsequent clinical course was typical, being marked by relapses and remissions responsive to prednisolone. Thus, described here is a woman in whom an acute onset of autoimmune chronic active hepatitis was clinically and histologically identified.

Adult↗

Cell-mediated immunity to hepatitis B virus antigens in mice: correlation of in vivo and in vitro assays.

Cell mediated immunity (CMI) to hepatitis B viral antigens was studied in BALB/mice after immunization with purified hepatitis B surface antigen (HBsAg), or core antigen (HBcAg), with adjuvants. The two in vitro assays for cell-mediated immunity (CMI), utilizing lymph node cells, were release of interferon after exposure to antigen, and blast transformation of lymphocytes, and the in vivo assay was ear swelling at 24 h after local injection of antigen. Immunization with HBsAg or HBcAg with adjuvants induced antigen-specific cutaneous reactivity; if no adjuvants were given, immunization with HBcAg, but not HBsAg, induced cutaneous reactivity. CMI could be adoptively transferred by lymph node cells, but for only a limited period after immunization with HbsAg or HBcAg. The ability of lymph node cells from mice immunized with HBV antigens to transfer adoptively CMI correlated well with their production of interferon after challenge with antigen in vitro, but less well with blastogenesis after challenge with antigen in vitro, or with cutaneous reactivity to antigen in the donor mouse. Reliable antigen-specific lymphokine release assays, rather than blast transformation of lymphocytes or cutaneous reactivity after antigen challenge, are required to assess CMI to HBV antigens in the mouse and, by inference, in man.

Adjuvants, Immunologic↗

Immunological abnormalities in asymptomatic homosexual men: correlation with antibody to HTLV-III and sequential changes over two years.

A prospective study on 100 homosexual male volunteers was designed to examine immunological function in relation to sexual activity and infection with the human T cell lymphotropic virus Type III (HTLV-III). Complete data were available for 71 men. In a comparison with 100 age-matched heterosexual men, the study group of 100 men had a significantly higher mean serum IgG level (12.1 +/- SD 2.7 g/l vs. 10.9 +/- 2.4 g/l, p less than 0.01) and a significantly lower mean number of CD4 (T4) cells (845 +/- 310 X 10(-6)/l vs. 1128 +/- 375; p less than 0.01). For the study group, seropositivity for anti-HTLV-III was present initially in 22 per cent and was associated with a higher mean level of serum IgG and lower mean number of CD4 cells. Among seropositive homosexual men a low CD4/8 ratio was attributable to low numbers of CD4 cells in those without lymphadenopathy and to high numbers of CD8 cells in those with lymphadenopathy. For the seronegative homosexual men, a low CD4/8 ratio as a result of an increased CD8 cell count was present in 12 of 60, and was associated with numerous sexual partners and semen culture positive for cytomegalovirus. In two seropositive subjects a low CD4/8 ratio due to a decrease in the CD4 cell count was predictive of the development of AIDS by some two years. For the 71 men with complete data over two years, indices of cell-mediated immunity, including mean counts of CD4 cells, the CD4/8 ratio, and score for recall of cutaneous delayed type hypersensitivity increased during the first year but not during the second year in both seropositive and seronegative subjects. These increases occurred in association with changes in sexual practices and activity, but could not be attributed to any one particular factor.

AIDS-Related Complex↗