Recovery of HTLV-III from contact lenses.
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Biomedical subjects
Publications and source records attributed to J Suni.
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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.
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Using a rabbit antiserum to a synthetic undecapeptide deduced from a cloned human retroviral gag-gene-related DNA sequence, we found a specific immunohistochemical reaction in all of 42 tested renal cell adenocarcinomas (RCC), while none of 17 similarly tested Wilms' tumors and 65 carcinomas at other sites were positive. The RCC included two cases that presented with distant metastases. It had not been possible to establish the origin of these until immunohistochemical staining revealed this typical reaction. Subsequent renal angiography disclosed the primary. In immunoblotting the antiserum detected an Mr 75,000 protein in RCC tissue, and this reaction was blocked by the undecapeptide. The usefulness of this protein as a tumor marker for RCC is discussed.
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.
A dot immunobinding (DIB) technique was applied to the demonstration of antibodies to human T-lymphotropic virus type III (HTLV-III). By this technique IgG antibodies to HTLV-III were demonstrated in six of six Swedish patients with acquired immune deficiency syndrome and in 37 of 39 (95%) Swedish homosexual men with persistent generalized lymphadenopathy but in none of 50 Swedish healthy blood donors. Findings obtained by this method showed complete concordance with those obtained by an enzyme-linked immunosorbent assay. All sera positive by DIB were also positive by Western blotting. The DIB assay is simple and well suited for screening of sera for HTLV-III antibodies.
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Proteins of purified rubella virus were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and immunoblotted with human sera and immunoglobulin class heavy-chain-specific peroxidase conjugates. The levels of rubella antibodies in these sera were predetermined by the radial hemolysis test, the density gradient centrifugation method for immunoglobulin M (IgM) antibodies, and IgG-, IgM-, and IgA-specific enzyme immunoassays. In immunoblotting, rubella-specific IgG antibodies reacted with both envelope glycoproteins (E1 and E2) and the capsid protein (C). In contrast, rubella IgM antibodies reacted predominantly with E1, whereas the specific reactivity of IgA antibodies was directed mainly to the capsid protein. Purified IgM rheumatoid factor added to IgG-positive, IgM-negative serum did not give false-positive reactivity in the immunoblotting test as it did in solid-phase enzyme immunoassays. The immunoglobulin class-specific reactivities with the different viral proteins are expected to have diagnostic applications.
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.
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.
The authors have previously demonstrated in syncytiotrophoblastic cells of human placenta, hydatidiform and destructive moles, and choriocarcinoma antigens reacting with antibodies to the endogenous feline retrovirus RD114 p30 and human T cell leukemia-lymphoma virus p19 proteins. The authors now report that a monoclonal IgG1 antibody (HPS-1), recognizing both syncytiotrophoblasts and RD114 p30, also reacts with an antigen in the tumor cell cytoplasm of all 27 renal cell adenocarcinomas studied. Positively stained antigenic material was also seen in the lumen of normal tubuli of tumor kidneys, suggesting its excretion into urine. None of 10 normal kidneys, 17 Wilms' tumors, 5 transitional cell carcinomas of the renal pelvis, 5 similar tumors of the urinary bladder, 20 adenocarcinomas of the cervix uteri, 20 adenocarcinomas of the corpus uteri, or 20 adenocarcinomas of the colon showed any positive staining. All 3 renal oncocytomas studied gave a positive staining reaction. In RD114 p30 radioimmunoassay antigenic activity was detected in the urine of renal cell adenocarcinoma patients in amounts up to 1.93 ng/mg protein, but not in the serum. After nephrectomy, a decline of the excreted antigen was observed, the preoperative values being 0.16 to 1.93 ng/mg protein and the postoperative ones ranging from immeasurable to 0.58 ng/mg protein. The patients with measurable postoperative urine values had clinically detectable distant metastases. The p30-related antigen may provide a marker for renal cell adenocarcinoma.
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In previous studies we detected retrovirus RD114 p30-related antigen in human placental syncytiotrophoblasts and antibodies in cord blood sera. We now report that a monoclonal IgG antibody specific for the p19 protein of human T-cell leukemia virus (HTLV) reacts with human syncytiotrophoblastic antigen. When used in the immunoperoxidase tissue-staining procedure, the monoclonal antibody reacted with the syncytiotrophoblastic cells in sections of all early placentas (less than 15 weeks of gestation), blighted ova and benign (hydatidiform mole) or malignant placental tumors (destructive mole, choriocarcinoma). In all cases the reactivity was mainly confined to the cytoplasm of the cells with syncytiotrophoblastic morphology. Normal embryonal or adult tissues tested were negative. In immunoblotting of cultured choriocarcinoma cells, anti-HTLV p19 detected a single polypeptide at mol.wt 28,000 from proteins separated by electrophoresis.
Purified retrovirus RD114 p30 was found to bind to the extracellular matrix proteins, fibronectin and laminin. The purified matrix proteins were immobilized onto polystyrene and the binding of p30 was quantitated using radioiodinated proteins and enzyme immunoassay (EIA). The dissociation constants were for the p30-fibronectin binding Kd = 5.3 X 10(-8) M and for the p30-laminin Kd = 7.3 X 10(-8) M. The molecular ratio in the binding from 4000 ng/ml of p30 was 1.9 mol per mol fibronectin and 2.5 mol per mol laminin. The interaction between fibronectin and RD114 retrovirus was also detected using a modified immunoblotting procedure.
Antibodies to a synthetic undecapeptide (NH2-Cys-Glu-Asn-Pro-Ser-Gln-Phe-Tyr-Glu-Arg-Leu-COOH), the sequence (except cysteine) of which was deduced from a previously reported cloned human retroviral gag-gene-related DNA sequence erv-1, were raised in rabbits. In immunohistochemical staining these antibodies reacted with normal human first-trimester placentas and with blighted ova and benign and malignant trophoblastic tumors (hydatidiform and destructive moles, choriocarcinomas) but not with any other normal embryonic or adult tissues tested. In all tissues the reactivity was mainly confined to cells with trophoblastic morphology. In immunoblotting the antibody detected an Mr 75,000 polypeptide in syncytiotrophoblasts isolated from first-trimester placentas and in three different lines of cultured choriocarcinoma cells. The undecapeptide blocked the reactivity of the antibody.