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Biomedical subjects

J Antonen

Publications and source records attributed to J Antonen.

At least 19 recordsLinked to original sources

Oral candidal infection as a sign of HIV infection in homosexual men.

The oral mucosae of 66 homosexual men were examined clinically and by means of cultivation to determine the presence of Candida infection. In addition, clinically detected mucosal changes were recorded and a biopsy specimen was obtained for the histopathologic classification. A total of forty one subjects (62%) showed clinical evidence of candidiasis. Fourteen (21%) of the sixty-six men were seropositive for human immunodeficiency virus (HIV). A total of thirteen of fourteen (93%) of the seropositive men and twenty-six of fifty-two (50%) of the HIV seronegative men had culture-confirmed oral candidiasis. In the latter group, oral candidiasis was clearly correlated to cigarette smoking. Clinical mucosal changes other than candidiasis were found in forty-five of the sixty-six subjects studied. The most frequent finding was trauma resulting from biting, which was usually localized on the cheek. Leukoplakia was found in twelve of sixty-six subjects, while cauliflower-like condylomas were present in 4 persons. The results emphasize the frequent occurrence of different oral lesions in subjects seropositive for HIV and in those at high risk for HIV infection. Oral examination in search for potential early manifestations of HIV infection in homosexual men is advocated.

Alcohol Drinking

Human milk fat globule antigen III D 5, steroid receptors and histopathologic parameters in breast cancer.

Immunohistochemical reactivity of mammary carcinomas with the monoclonal human milk fat globule (HMFG) antibody III D 5, and the estrogen receptor (ER) and progesterone receptor (PR) status were compared with the histopathology of primary breast cancer. The reactivity with III D 5 has earlier been shown to be associated with the estrogen receptor status of tumours and with a favourable prognosis. The reactivity of tumours with III D 5, as well as the presence of ER and PR correlated significantly with the histological features of differentiation; histological grade, nuclear grade, tumour necrosis and lymphoid infiltration. Reactivity with III D 5 correlated with all these parameters, while the presence of ER did not correlate with the nuclear grade and that of PR correlated only with the nuclear grade and the lymphoid infiltration of tumours. Reactivity of III D 5 may thus have prognostic and therapeutic implications in the management of breast cancer.

Adult

Defective autologous mixed leukocyte reaction in newly diagnosed type 1 diabetes mellitus.

We studied autologous mixed leukocyte reaction (AMLR) in type 1 (insulin-dependent) diabetes mellitus (IDDM) patients, their healthy siblings and healthy schoolchildren, Blood samples from the patients were drawn within 1 week after hospitalization and 2 months later. AMLR was significantly depressed in the patients when compared to healthy siblings or other healthy controls. In addition, the mean AMLR responsiveness of the healthy control group exceeded that of healthy siblings. The production of IL-2 in AMLR was impaired in the patient group and the defective AMLR could be restored by addition of exogenous IL-2 in 7-10 patient cultures. However, in 3-10 patients addition of IL-2 induced no enhancement of proliferation. While the patients in general had raised levels of activated T lymphocytes these three patients had higher numbers of activated T cells than other patients. Defective AMLR and presence of activated T cells may be related and may play a role in the pathogenesis of IDDM.

Adolescent

Long latency precedes overt seroconversion in sexually transmitted human-immunodeficiency-virus infection.

Signs of latent HIV infection were sought in stored serum samples collected before overt seroconversion, confirmed by enzyme-linked immunosorbent assay (ELISA), from 9 subjects with human-immunodeficiency-virus (HIV) infection, in serum from 25 seronegative sexual partners of HIV-seropositive men and from 23 other seronegative, homosexually active men. Free HIV antigen and/or low-titre antibodies to recombinant structural (core, env) or non-structural (3' orf, sor, tat) proteins were seen 6-14 months before seroconversion in all 9 subjects who seroconverted. Antibodies against core proteins detected by western blot were usually the first sign of latent HIV infection. 5 of the 25 ELISA-negative exposed partners have shown HIV antigenaemia and antibodies against core proteins for 16-34 months. By in-situ hybridisation, HIV-specific RNA was detected in peripheral-blood non-lymphoid mononuclear cells in some of the latently infected partners. All subjects with latent HIV infection had normal numbers of T4 lymphocytes but half of them lost their in-vitro proliferative T-cell response to a recall antigen (purified protein derivative of tuberculin). Early HIV infection, characterised by a low-level and restricted antibody response towards HIV core and regulatory proteins, seems mainly to affect antigen-presenting cells.

Acquired Immunodeficiency Syndrome

The use of an HTLV-I-infected human T-cell line (ATH8) in an interleukin-2 bioassay.

Biological interleukin-2 (IL-2) assays require cells that proliferate only in the presence of IL-2. The most often used human cells for this purpose have been phytohaemagglutinin (PHA)-stimulated buffy coat lymphocytes made dependent on IL-2. The results obtained by this T-blast method have not been easily reproducible and/or comparable due to differences in individual buffy coat batches. Murine cytotoxic T-cell lines (CTLL and CTLL-2) have been widely used in human IL-2 assays, but there remains a need for a human cell line. We have developed an IL-2 bioassay, based on the use of a human HTLV-I-infected Th-cell line, ATH8. These cells express IL-2 receptor and are totally dependent on extrinsic IL-2 for proliferation. The results of the ATH8 IL-2 assay were reproducible and comparable to those obtained with successful T-blast assays. ATH8 cells do not require a prolonged culture period before they are suitable for the IL-2 assay as do T-blasts.

Biological Assay

Acute multiple sclerosis exacerbations are characterized by low cerebrospinal fluid suppressor/cytotoxic T-cells.

The present study describes peripheral blood (PB) and CSF T-lymphocyte subpopulations in 55 MS patients with and without acute exacerbation and compares the results with those obtained from 8 with CNS infections and 45 with other neurological disorders or symptoms (OND). The MS patients were most strongly characterized by a decline of their CSF suppressor/cytotoxic T-cells, which was most profound during acute exacerbations. The proportional amount of CSF helper/inducer T-cells (Th) was higher in both MS group than in the OND group, but not different from that of the CNS infection group. No statistically significant change in the CSF Th-cells during exacerbations was seen. MS patients without an exacerbation had somewhat higher levels of their PB Th-cells than the patients with OND, but otherwise no differences in the PB T-cell subsets were seen.

Cerebrospinal Fluid

The validity of immunological studies in human immunodeficiency virus infection: a three-year follow-up of 235 homo- or bisexual persons.

During a three-year follow-up study of 235 risk-group people living in Finland, we found a slow increase in the proportion of HIV seropositives (from 9.8% to 14.0%) and a slow but continuous advance in symptoms typical of HIV infection among them. The first immunological changes after HIV seroconversion were an increase in Ts-cells and a decline in antigen-induced T-cell functions (proliferation, IL-2 production). A further decline in antigen-induced responses was seen before early clinical symptoms and signs of HIV infection developed. During later phases of HIV infection the decrease of Th-cells and the elevation of serum Beta-2 microglobulin correlated most strongly with the progression of HIV infection. The mitogen-induced lymphocyte functions of the HIV-infected correlated to Th-cell levels, while the antigen-induced proliferation and IL-2 production showed correlation neither to Th-cells nor to Ts-cells. The poor antigen-induced T-cell responses might be caused by abnormally functioning monocytes, known to be infected by HIV. Our results suggest that in HIV infection there is a continuous but slow disease progression, although individual variation may be great. The immunological parameter best predicting the prognosis of an infected person in the early phases of infection was the antigen-induced lymphocyte functions, and later the amount of Th-cells.

Acquired Immunodeficiency Syndrome

T-lymphocyte subpopulation levels and immunoglobulin changes in the cerebrospinal fluid of patients with neurologic disorders.

Immunologic mechanisms are thought to play an important role in the pathogenesis of multiple sclerosis (MS). In this study we examined cerebrospinal fluid (CSF) samples of 29 patients with MS and of 24 patients with other neurological disorders. An elevated T-helper (Th)/T-suppressor (Ts) ratio was typical for the CSF of patients with MS. There was a clear positive correlation between the percentage of Th cells and the existence of oligoclonal bands in the CSF. On the other hand, the percentage of Ts cells correlated negatively with the existence of oligoclonal bands in the CSF. The imbalance of CSF T-lymphocyte subpopulations may be one of the fundamental defects in MS, and the observed alterations in CSF immunoglobulin synthesis pattern might only reflect these changes.

Cerebrospinal Fluid Proteins

Neutralizing antibodies in HIV (HTLV-III) infection: correlation with clinical outcome and antibody response against different viral proteins.

Sequential serum samples, collected over a 2-3 year follow-up period, of 28 HIV-infected individuals were tested for the presence of neutralizing antibodies against one HIV isolate, HTLV-IIIB, and titrated, by Western blotting, against different HTLV-III specific proteins. Neutralizing antibodies were found in 66% of the samples tested and highest neutralization titres observed in cases with lymphadenopathy syndrome. Antibody titres against the viral proteins also seemed to be highest in cases with LAS. Neutralization titres correlated well with antibodies to envelope glycoproteins gp41 and gp120 and to one of the core proteins, p17. An increase in neutralization titre during the follow-up period was associated with a stable clinical course. Furthermore, the occurrence of antibodies directed against the external envelope glycoprotein (gp120) in the initial serum sample correlated well with a stable clinical course. The results suggest that neutralizing activity in the serum, particularly that evoked against gp120, may have some prognostic significance, and that several distinct antigenic epitopes on the virus may be a target for neutralizing antibodies.

Acquired Immunodeficiency Syndrome

Seropositivity to LAV/HTLV-III in 11 European countries.

The ECP Working Group on AIDS has evaluated data on seropositivity to LAV/HTLV-III supplied by members in II Western European countries. The period covered is 1981-84. The rise in LAV/HTLV seropositivity parallels the incidence of cases of AIDS in the different countries. LAV/HTLV now spreads freely within Europe and spread has become less dependent upon promiscuity. The epidemic is about to enter Eastern Europe. Intravenous drug abusers appear to be the risk group experiencing the most rapid spread at present. Furthermore, seropositivity in males and females outside the traditional risk groups seems on the rise, and as in the US the percentage seronegative in individuals with PGL is quite high. AIDS is rapidly becoming a major cause of cancer in young adults. A coordinated European preventive effort is urgently needed.

Acquired Immunodeficiency Syndrome

Interleukin 2 production in HTLV-III/LAV infection: evidence of defective antigen-induced, but normal mitogen-induced IL-2 production.

We studied mitogen- and antigen-induced interleukin 2 (IL-2) production in HTLV-III/LAV infected and non-infected individuals and compared the results with T cell subpopulations, and with mitogen- and antigen-induced DNA synthesis and production of leucocyte migration inhibitory factor (LIF) in order to understand the controversial findings related to IL-2 production in HTLV-III/LAV infection. The HTLV-III/LAV antibody positive group showed immunological defects: low T helper (Th) cells, high T-suppressor (Ts) cells, reduced mitogen- and antigen-induced DNA-synthesis, but LIF production comparable to the HTLV-III/LAV antibody negative group. The total amount of IL-2, produced either as a response to a mitogenic stimulus or as a response to a soluble antigenic (purified protein derivative of tuberculin, PPD) stimulus, was lower in the HTLV-III/LAV antibody positive group. However, adjusting the IL-2 production to the amount of Th-cells showed that the IL-2 produced by a standard number of Th-cells after mitogen induction was similar in HTLV-III/LAV infected and non-infected individuals. In contrast, the ability of Th-cells of infected persons to produce IL-2, or to proliferate as a response to a soluble antigenic stimulus, was considerably diminished. We conclude that HTLV-III infection leads to a selective incapability to mount a specific Th-cell response either due to an intrinsic defect in the Th-cell population or due to metabolic and/or functional disturbances in antigen-processing and presenting accessory cells.

Acquired Immunodeficiency Syndrome

Diversity of clinical spectrum of HTLV-III infection.

In a prospective follow-up volunteer study lasting 4 to 16 months, 17 of 200 homosexual men living in Finland had antibodies to human T-lymphotrophic virus type III (HTLV-III). 1 man who initially had a low titre of HTLV-III antibodies became seronegative within 6 months without any symptoms developing, and a seronegative man became seropositive. 14 men had high titres of HTLV-III antibodies when they first joined the study and during the study titres rose in all other HTLV-III-positive men except those with AIDS. Initially 9 men were symptom-free, 3 had lymphadenopathy syndrome (LAS), 3 had AIDS-related complex (ARC), and 2 had AIDS. During follow-up LAS developed in 3 symptom-free HTLV-III positive men but none of those with LAS or ARC progressed to AIDS. Most HTLV-III-positive men, including those who were otherwise symptom-free, had mucocutaneous lesions generally associated with immune deficiency. Regardless of the symptoms, those with increasing HTLV-III antibody titres showed lowered T helper/T suppressor ratios, decreased numbers of T helper cells, and/or diminished responses to tuberculin antigen (PPD). These results suggest that the clinical spectrum of HTLV-III infection ranges from transient infection through chronic provirus state, asymptomatic virus producer state, LAS or ARC, and rarely full-blown AIDS. Cofactors probably determine the final outcome of infection in the individual.

Acquired Immunodeficiency Syndrome

Immune functions in homosexual men with antibodies to HTLV-III in Finland.

The occurrence of HTLV-III antibodies in a voluntary group of 175 homosexual men in a low risk AIDS area was studied, and the findings were correlated to clinical, virological, immunological and lifestyle parameters. Fifteen of 175 men had HTLV-III antibodies; two of these had AIDS, five had LAS and two had enlarged lymph nodes. In the HTLV-III antibody negative group, no signs of AIDS or pre-AIDS were seen during a 10 month follow-up. In HTLV-III antibody positive individuals, low TH/TS ratio was mainly due to decreased number of TH cells. Most HTLV-III antibody positive cases had low responses to a specific antigen, PPD, while responses to the mitogens PHA and PWM were only slightly affected. In HTLV-III antibody negative cases, 13% had a low TH/TS ratio, mostly due to elevation of TS cells. In this group, mitogen and antigen responses were normal or only slightly affected. The results reinforce the causal relationship between HTLV-III and AIDS and suggest that the cells primarily affected by the virus infection are TH cells, responsible for antigen specific responses. Longitudinal studies are required to find out, what is the relationship of immune response to the development of clinical AIDS in HTLV-III infected individuals.

Acquired Immunodeficiency Syndrome

Clinical and immunological findings in HTLV-III infection.

Clinical, immunological, microbiological, virological, and lifestyle parameters were followed in 200 homosexual men living in Finland. The subjects were seen at 3- to 6-month intervals starting in summer 1983. Human T-cell lymphotropic virus III (HTLV-III) antibodies detected by enzyme immunoassay and confirmed by Western blotting were seen in 18 (9%) of the cases. Initially two cases had acquired immunodeficiency syndrome, three had acquired immunodeficiency syndrome-related complex, three had lymphadenopathy syndrome, and ten were asymptomatic. During the follow-up two asymptomatic cases developed lymphadenopathy syndrome and three developed enlarged lymph nodes. Immunological studies revealed decreased T-helper cell values and/or T-helper/suppressor ratios in all clinical categories, the findings being more severe and progressive in the symptomatic cases. The finding most clearly distinguishing HTLV-III antibody positive cases from the antibody negative ones was a decreased response to a specific recall antigen, purified protein derivative of tuberculoprotein. Responses to mitogens phytohemagglutinin and pokeweed mitogen were also decreased, but to a lesser extent. The primary immunological defect associated with helper T-cell infection by HTLV-III thus seems to be loss of antigen specific immune responses. It is suggested that this is the result of previous antigenic stimulation of HTLV-III infected T-helper cells and that the cellular destruction is associated with initial mitotic activity.

Acquired Immunodeficiency Syndrome

Immunological findings associated with HTLV-III antibody positivity.

In order to evaluate the immunological findings associated with HTLV-III virus infection, T-lymphocyte subpopulations and lymphocyte stimulation responses were studied in a voluntary group of 174 homosexual men living in Finland. Antibodies against HTLV-III were found in 17 individuals. Decreased T-helper/T-suppressor ratio and low responses to mitogens (phytohaemagglutinin, pokeweed mitogen) and a specific antigen (purified protein derivative of tuberculin) were typical for HTLV-III antibody positive individuals. The reason for this decreased Th/Ts ratio was the low level of T-helper cells. In the HTLV-III antibody negative group, where a low Th/Ts ratio was occasionally seen, it was due to elevated T-suppressor cells. The low T-helper cell values were in good correlation with the poor clinical status of these persons and with low stimulation responses.

Acquired Immunodeficiency Syndrome

Immunosuppression in homosexual men seronegative for HTLV-III.

Clinical, microbiological, and lifestyle patterns in homosexual men showing in vitro immunological abnormalities were studied and related to the susceptibility to human T-lymphotropic virus type III (HTLV-III) infection. In a cohort of male homosexual volunteers in Finland, 90% were HTLV-III antibody negative. Ten % of the HTLV-III negative cases showed decreased T-helper/suppressor cell ratios, mostly due to elevated numbers of T-suppressor cells. In this immunosuppressed group, more signs of diarrhea, intestinal giardiasis, genital warts, and hepatitis B were observed than in the other HTLV-III antibody-negative study subjects. The type of sexual practice was not associated with the in vitro immune abnormalities. During a follow-up of up to 16 months, 4 initially HTLV-III antibody negative cases showed seroconversion. Three of these had inverted T-helper/suppressor cell ratios prior to the seroconversion. It is concluded that persons showing in vitro immunosuppression are more susceptible to HTLV-III infection when being exposed to the virus or else alteration in T-cell subsets signals a pre-antibody-positive or early phase of HTLV-III infection.

Antibodies, Viral