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J Schüpbach

Publications and source records attributed to J Schüpbach.

72 records · Page 4Linked to original sources

[Retroviruses, human tumors and autoimmune diseases].

Retroviruses are known to cause a variety of naturally occurring disorders in animals. These include various types of cancer, immune deficiencies, and degenerative and autoimmune disorders. In man, retroviruses are the causal agents of adult T-cell leukemia/lymphoma and AIDS. In addition, serologic evidence suggests the involvement of retroviruses in a variety of other human disorders including leukemias and lymphomas, and autoimmune as well as psychiatric and neurologic disorders.

Acquired Immunodeficiency Syndrome↗

Evidence for HTLV-I associated with mycosis fungoides and B-cell chronic lymphocytic leukemia.

Human T-cell lymphotropic virus type I (HTLV-I) is a human retrovirus that can transform T-helper lymphocytes and is etiologically associated with adult T-cell lymphoma/leukemia. Mycosis fungoides represents a primary cutaneous lymphoma of helper T-cell origin, while chronic lymphocytic leukemia is generally considered to be a neoplastic B-lymphocyte disorder. Our patient had HTLV-I with coexistent mycosis fungoides and B-cell chronic lymphocytic leukemia. The concurrent lymphoid proliferations may represent HTLV-I-associated abnormalities of immunoregulation.

Aged↗

Specificity of human immunodeficiency virus (LAV/HTLV-III)-reactive antibodies in African sera from southeastern Tanzania.

The prevalence of antibodies to human immunodeficiency virus (HIV = LAV/HTLV-III) in a rural population from the Ifakara area in southeastern Tanzania was investigated. Sera from 286 individuals collected from 1982 to 1984 in connection with a study on liver disorders were tested by an ELISA. Fifty-two (18.2%) of the sera were found positive. While the positives were largely confirmed by one commercial ELISA, they were completely negative by two others. Confirmatory testing by Western blot and competition Western blot showed that the reactivity detected by more sensitive of these assays was largely due to IgG antibodies binding to the HIV core (gag) proteins p17, its precursor p55 and, in some cases, p24. These tests also indicated, however, that the reactive antibodies could not have been elicited by HIV, but possibly by an unknown retrovirus or another cross-reactive agent. Thus, by 1984, the area investigated was largely free of HIV infection, but a significant proportion of its population may harbor another retrovirus of unknown pathogenicity.

Acquired Immunodeficiency Syndrome↗

Intra-blood-brain-barrier synthesis of HTLV-III-specific IgG in patients with neurologic symptoms associated with AIDS or AIDS-related complex.

Intra-blood-brain-barrier production of virus-specific antibody is good evidence of infection within the blood-brain barrier. Patients with the acquired immuno-deficiency syndrome (AIDS) have an increased incidence of neurologic abnormalities--i.e., unexplained, diffuse encephalopathy manifested clinically as chronic progressive dementia. To define the role of human T-cell lymphotropic virus Type III (HTLV-III), the etiologic agent of AIDS, in the pathogenesis of neurologic dysfunction, we compared cerebrospinal fluid and serum from patients with neurologic symptoms associated with AIDS and the AIDS-related complex for the presence of antibodies directed against HTLV-III. Antibodies directed against HTLV-III antigens were detected by four immunologic tests: a fixed-cell immunofluorescence assay, an enzyme-linked immunosorbent assay, immunoblots of viral lysates, and immunoprecipitation of cellular lysates. All patients were seropositive, and 22 of 23 (96 per cent) had HTLV-III-specific antibodies in their cerebrospinal fluid. Unique oligoclonal IgG bands were detected in the cerebrospinal fluid, and the rate of IgG synthesis within the blood-brain barrier was elevated. In eight of nine patients tested, the enzyme-linked immunosorbent assay showed that the percentage of HTLV-III-specific IgG in cerebrospinal fluid was higher than in serum, suggesting that HTLV-III infection of neurologic tissue occurs in the majority of patients with neurologic disease associated with AIDS or its related complex.

Acquired Immunodeficiency Syndrome↗

[HTLV-III antibodies and risk factors for healthy homosexuals in Zurich].

Sera of 100 healthy homosexual men were tested for antibodies to AIDS virus HTLV-III. Significant differences were found between 45 seropositive and 55 seronegative men, such as a higher number of sexual partners per year, more contacts with AIDS patients, positive serological markers for syphilis, and reduced skin reaction after intradermal application of 7 recall antigens.

Adult↗

[Prevalence of antibodies against HTLV-III in various regions in Switzerland].

Acquired immune deficiency syndrome (AIDS) has been etiologically linked with the human T-cell lymphotropic virus HTLV-III. In a study on the prevalence of antibodies to this virus in Switzerland, sera from 941 individuals were collected in 5 major urban areas (Basel, Berne, Geneva, Lausanne and Zurich) in 1983 and 1984. All sera were tested by ELISA and the majority also by Western blot. We found an antibody prevalence of 100% among 22 cases of AIDS, of 94% among 48 cases of AIDS-related complex (ARC), and of 57% among 14 homosexual contacts of AIDS patients. Among 55 sera collected from i.v. drug addicts in 1984, 53% were positive, whereas the rate had been 36% among 103 sera collected in 1983. The rate was 19% among 227 sera collected from asymptomatic active homosexuals in 1984, against 10% among 40 sera collected in 1983. 8% positives were found among 98 patients with various types of viral hepatitis. In addition, 4% of 84 sera of individuals from Equatorial Africa were positive. No positives were found among 15 sera of individuals from other African regions, among 32 sera of persons from various regions of Asia, and among 203 Swiss blood donors. These results demonstrate the high and increasing rate of HTLV-III infection among groups at risk for AIDS, and suggest that HTLV-III-related diseases will be a serious problem in the years ahead.

Acquired Immunodeficiency Syndrome↗

Antibodies to HTLV-III in Swiss patients with AIDS and pre-AIDS and in groups at risk for AIDS.

We tested serum samples from Swiss subjects by three different assays based on enzyme-linked immunosorbent assay (ELISA) and Western blot techniques for antibodies to proteins associated with the recently discovered human T-cell leukemia/lymphoma virus HTLV-III, the putative etiologic agent for the acquired immunodeficiency syndrome (AIDS). Of 10 patients with AIDS and 10 with pre-AIDS, all were antibody-positive. Furthermore, 37 of 103 intravenous-drug addicts (36 per cent), 4 of 40 healthy homosexual men (10 per cent), 7 of 83 patients with various types of hepatitis (8.4 per cent), but none of 83 healthy blood donors or 10 other controls were antibody-positive. Antibodies to the major viral protein p24 were found consistently and at high titers in the seropositive members of the groups at risk and in those with pre-AIDS but were dramatically reduced in patients with AIDS. In contrast, antibodies to another virus-associated protein, p41, were present in all cases of AIDS and pre-AIDS but were absent in nearly 10 per cent of seropositive persons at risk. Whereas p41 and p24 thus appear to be the targets of choice for future screening tests, the ELISA test that is currently available is a useful screening tool.

Acquired Immunodeficiency Syndrome↗

[Acquired immunodeficiency syndrome in a child of Swiss origin whose mother died from AIDS].

Report of a now 2 8/12-year-old girl, who presented at the age of 8 months with chronic progressive pneumonia, mucocutaneous candidiasis, diarrhea, failure to thrive and a non-progressive paraplegia. The child's mother presented AIDS with pneumocystis carinii pneumonia and progressive general paralysis one year after the beginning of the child's disease and died within a few months. Additional findings in the child include lymphopenia, hyperimmunoglobulinemia, cutaneous anergy and an abnormal T helper/T suppressor cell ratio. HTLV-III antibodies were positive (ELISA and Western blot virus strip RIA). Prophylactic treatment with Co-trimoxazole relieved pulmonary infections but failure to thrive remained unchanged in spite of a continuous nutritional support. A vertical mode of transmission of AIDS from mother to child seems very probable.

Acquired Immunodeficiency Syndrome↗

Seroepidemiological studies of human T-lymphotropic retrovirus type III in acquired immunodeficiency syndrome.

In a double-blind study, sera of 34 patients with acquired immunodeficiency syndrome (AIDS), 19 patients with lymphadenopathy syndrome, and 14 homosexual men with an increased risk of AIDS were screened for antibodies to proteins of the novel human T-lymphotropic retrovirus (leukaemia virus), HTLV-III, recently isolated from cultured T cells of AIDS patients. On a combination of a convenient and rapid enzyme-linked immunosorbent assay and a more sensitive electroblot (Western) assay, 100% of the AIDS sera were scored positive. Similarly, 84% of the lymphadenopathy patients were found to have serum antibodies to HTLV-III. A lower, but significant, proportion (21%) of healthy homosexual men with an increased risk of AIDS were also positive. No heterosexual controls, including those with heterophile antibodies during the course of infectious mononucleosis and patients with T-cell or B-cell lymphoma, had antibodies to HTLV-III. The results strongly indicate that the antibodies to HTLV-III are diagnostic of AIDS or indicate significant risk of the disease, and suggest that HTLV-III is the primary cause of human AIDS.

Acquired Immunodeficiency Syndrome↗

Antigens on HTLV-infected cells recognized by leukemia and AIDS sera are related to HTLV viral glycoprotein.

Cross-reactive antigens of molecular size of 61,000 to 68,000 daltons are found on the surface of human cells infected by human T-cell leukemia-lymphoma virus (HTLV). They are recognized by antibodies from patients with adult T-cell leukemias and lymphomas, from healthy carriers of HTLV, and from patients with the acquired immunodeficiency syndrome (AIDS). The latter finding has been one of the major reasons for suggesting an association of HTLV with AIDS. However, whether these antigens are of cellular or viral origin has not been clear. These antigens have now been shown to be associated with the presence of viral proteins in the cells, and a cross-reactive glycoprotein of molecular size of 46,000 daltons has been found to be a consistent structural part of viruses purified from several HTLV-producer cell lines. The findings thus suggest a viral (HTLV) origin of these antigens.

Acquired Immunodeficiency Syndrome↗

Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS.

The two main subgroups of the family of human T-lymphotropic retroviruses (HTLV) that have previously been characterized are known as HTLV-I and HTLV-II. Both are associated with certain human leukemias and lymphomas. Cell surface antigens (p61 and p65) encoded by HTLV-I are frequently recognized, at low titers, by antibodies in the serum of patients with acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that precede AIDS (pre-AIDS). This suggests an involvement of HTLV in these disorders. Another subgroup of HTLV, designated HTLV-III, has now been isolated from many patients with AIDS and pre-AIDS. In the studies described in this report, virus-associated antigens in T-cell clones permanently producing HTLV-III were subjected to biochemical and immunological analyses. Antigens of HTLV-III, specifically detected by antibodies in serum from AIDS or pre-AIDS patients and revealed by the Western blot technique, are similar in size to those found in other subgroups of HTLV. They include at least three serologically unrelated antigenic groups, one of which is associated with group-specific antigens (p55 and P24) and another with envelope-related (p65) proteins, while the antigens in the third group are of unknown affiliation. The data show that HTLV-III is clearly distinguishable from HTLV-I and HTLV-II but is also significantly related to both viruses. HTLV-III is thus a true member of the HTLV family.

Acquired Immunodeficiency Syndrome↗

Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS.

In cats, infection with T-lymphotropic retroviruses can cause T-cell proliferation and leukemia or T-cell depletion and immunosuppression. In humans, some highly T4 tropic retroviruses called HTLV-I can cause T-cell proliferation and leukemia. The subgroup HTLV-II also induces T-cell proliferation in vitro, but its role in disease is unclear. Viruses of a third subgroup of human T-lymphotropic retroviruses, collectively designated HTLV-III, have been isolated from cultured cells of 48 patients with acquired immunodeficiency syndrome (AIDS). The biological properties of HTLV-III and immunological analyses of its proteins show that this virus is a member of the HTLV family, and that it is more closely related to HTLV-II than to HTLV-I. Serum samples from 88 percent of patients with AIDS and from 79 percent of homosexual men with signs and symptoms that frequently precede AIDS, but from less than 1 percent of heterosexual subjects, have antibodies reactive against antigens of HTLV-III. The major immune reactivity appears to be directed against p41, the presumed envelope antigen of the virus.

Acquired Immunodeficiency Syndrome↗

Demonstration of viral antigen p24 in circulating immune complexes of two patients with human T-cell leukaemia/lymphoma virus (HTLV) positive lymphoma.

Circulating immune complexes from two patients with human T-cell leukaemia/lymphoma virus (HTLV)-related lymphoma were shown to contain the major internal antigen of the virus, p24. The amount of complex-bound p24 in sequential serum samples correlated roughly with tumour cell mass. Small amounts of complex-bound p24 were detected in samples before a relapse became clinically manifest. Measurement of complex-bound p24 in patients with HTLV-associated lymphomas and leukaemias might thus be helpful in management of malignancies and offer the possibility of detecting imminent relapse and preventing it by intensification of treatment.

Antigen-Antibody Complex↗

HTLV-III: the etiologic agent of AIDS.

A retrovirus belonging to the family of human T-cell leukemia/lymphoma virus (HTLV) was isolated from several patients with acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC) and asymptomatic homosexual males at increased risk of developing AIDS. This new virus was designated HTLV-III. A serological screening procedure incorporating an enzyme-linked immunosorbent assay (ELISA) and a radioimmunoassay using a Western blot technique was developed employing disrupted HTLV-III as the antigen source. These assays identified serum antibodies to HTLV-III antigens in almost all patients with AIDS, greater than 90% patients with ARC and about 40% of homosexual males at risk for developing AIDS. In a study of transfusion associated AIDS (TA-AIDS) all 19 of the TA-AIDS cases had antibodies to HTLV-III. Similarly 31 of 35 high risk donors who donated to cases of TA-AIDS had antibodies to HTLV-III. All four of the antibody negative high risk donors donated to cases that received blood from at least one other high risk donor. In contrast only 2 of 255 other donors were antibody positive. The data clearly indicate that TA-AIDS cases developed the disease as a result of transmission of HTLV-III through contaminated blood and that HTLV-III is the primary etiologic agent of AIDS.

Acquired Immunodeficiency Syndrome↗

Antibodies against three purified structural proteins of the human type-C retrovirus, HTLV, in Japanese adult T-cell leukemia patients, healthy family members, and unrelated normals.

The immunological relationship of human T-cell leukemia/lymphoma virus (HTLV) and the virus found in Japanese adult T-cell leukemia/lymphoma (ATL) was investigated in detail by testing the specific binding of serum antibodies from Japanese ATL patients and normal Japanese donors to the purified HTLV proteins p24, p19, and p15. Sera were prescreened for antibodies to p24. Of those positive, 67% of the ATL sera and 78% of the normal sera were further shown to have antibodies against p19. In both groups 17% had antibodies to p15. Generally, the average antibody titers were twice as high in ATL as in normal sera. Competition radioimmunoprecipitation assays done with various sera and involving HTLV-producing cells, virus-positive cells from a Japanese ATL patient, and virus-positive cultured T cells of one of his healthy family members as competing materials demonstrated no differences between the p24, p19, and p15 found in these cells. These results provide strong and detailed immunological evidence that the human retrovirus isolates first made from US patients with cutaneous T-cell malignancies, and those made later in Japanese ATL are either identical or very closely related strains of the same virus, HTLV, a finding verified in other detailed analyses of the HTLV genomes of the respective isolates. To date only HTLV-II, isolated from a US case of hairy-cell leukemia of a T-cell type, is a distinct additional human retrovirus class.

Adolescent↗

Antibodies against three purified proteins of the human type C retrovirus, human T-cell leukemia-lymphoma virus, in adult T-cell leukemia-lymphoma patients and healthy Blacks from the Caribbean.

Six black patients of Caribbean origin with adult T-cell leukemia-lymphoma, 18 of their healthy family members and relatives, and 337 healthy black individuals from the Caribbean were investigated for the presence of serum antibodies against human T-cell leukemia-lymphoma virus (HTLV). Three distinct structural proteins of this virus with molecular weights of 24,000, 19,000, and 15,000 were purified, radiolabeled, and used in radioimmune precipitation assays. Five of the patients, three of the family members (two of them spouses), and 11 of the normals had specific antibodies against at least the proteins with molecular weights of 24,000 and 19,000. High antibody titers against these proteins were often associated with antibodies against the protein with a molecular weight of 15,000. In all cases, antibody titers against this protein were considerably lower than those against the proteins with molecular weights of 24,000 and 19,000. HTLV is highly associated with Caribbean adult T-cell leukemia-lymphoma and is also endemic among the normal Caribbean population. By comparison of the frequencies of anti-HTLV positives among family members of patients and the normal population, we conclude that infection by HTLV occurs in a horizontal way and at least in the West Indian black and Japanese population probably without a requirement for uncommon genetic factors.

Adult↗

[A possible new prognostic criterium for acute myelocytic leukemia: speed of the titer increase of antiviral antibodies after virus oncolysate injections].

In a study conducted by the Swiss Group for Clinical Cancer Research, 28 patients with acute myelogenous leukemia in complete remission were treated by chemotherapy and viral oncolysate (i.e. formalin treated fowl plague virus infected allogenous leukemia cells). Patients with a slow rise and low maximal titers of antiviral antibodies in the sera proved to have longer remissions than those with a prompt and high rise. Several patients showed association of antiviral antibody changes in the serum with the percentage of myeloblasts in the bone marrow. Determination of the antiviral antibody titer slope after repeated immunization by viral oncolysate can therefore be used for prognosis in patients with acute myelogenous leukemia in remission, and may be helpful in detecting inadequately treated patients.

Antibodies, Viral↗