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Biomedical subjects

R Hehlmann

Publications and source records attributed to R Hehlmann.

At least 235 records · Page 13Linked to original sources

Antigens and circulating immune complexes related to the primate retroviral glycoprotein SiSV gp70: prevalence and distribution in human sera.

We have shown previously that antigens and also circulating immune complexes related to the primate retroviral envelope glycoprotein SiSV gp70 correlate with early mortality and survival of 56 patients with acute leukemias and chronic myelogenous leukemia in blast crisis. The prevalence and general distribution of these antigens and immune complexes in human sera was therefore of obvious interest. We now report an analysis of a total of 200 sera from 166 patients. Of these 113 sera were obtained from 84 patients with acute or chronic leukemias and 87 from 82 non-leukemic subjects, including laboratory workers and patients with non-leukemic neoplasias. Antigens and immune complexes were determined by enzyme-linked immunosorbent assays (ELISA). The anti-SiSV gp70 antiserum used predominantly recognized the protein moieties of the glycoproteins. The distribution of SiSV gp70-related antigens and immune complexes was similar among leukemic and non-leukemic sera. The prevalence of SiSV gp70-related antigens was 53% and of SiSV gp70-related immune complexes 49% in all sera. SiSV gp70-related antigens were detected in a somewhat higher proportion of non-leukemic (69%) than leukemic sera (40%), whereas SiSV gp70-related immune complexes and cross-reactive antibodies were more evenly distributed in leukemic and non-leukemic sera (in 46 and 51% of leukemic and 54 and 51% of non-leukemic sera). Presence of antigens correlated with presence of SiSV gp70-related immune complexes in 71% of all sera, but in 13% of all sera antigens were detectable only by determining SiSV gp70-related immune complexes. Total circulating immune complexes did not correlate with SiSV gp70-related immune complexes. The origin and pathophysiological role of the antigens are discussed.

Acute Disease↗

Immunopathology of AIDS (acquired immune deficiency syndrome) observations in 75 patients with pre-AIDS and AIDS.

Sequential changes in the morphology of immunocompetent and other organs, in the accompanying immunocytological and immunovirological measurements are described in 75 patients with lymphadenopathy syndrome and with AIDS. The data presented demonstrate a stepwise development of the disease from a hyperimmunization syndrome to T-cell immune deficiency. Excessive antigenic stimulation by a large number of infectious organisms or by transfusion of blood and blood products account for antigenic overloading and hyperimmunization. Among such infectious organisms are certain viruses which per se interfere with cells of the immune system as for instance Epstein-Barr virus, cytomegalovirus, and HTLV3. Developing immunological incompetence will favor the persistence of these and other infectious organisms enhancing the damage of the immune reactivity and finally allow lethal infections or malignant tumors to occur.

Acquired Immunodeficiency Syndrome↗

Prevalence of antibodies to HTLV-III in AIDS risk groups in West Germany.

The prevalence of antibodies to human T-lymphotropic virus III was determined in acquired immunodeficiency syndrome (AIDS) risk groups by an enzyme linked immunosorbent assay and confirmatory tests in four different areas in West Germany. Twenty-four of 28 homosexual AIDS patients (86%), 24 of 33 homosexual patients with lymphadenopathy syndrome or AIDS related complex (73%), and 44 of 113 asymptomatic homosexuals at risk for AIDS (39%) were seropositive. In three groups of hemophiliacs, 8 of 35 in 1983 (23%), 25 of 65 in early 1984 (39%), and 19 of 23 in late 1984 (83%) showed positive results. Two sera from 36 polytransfused patients were also positive, whereas 36 selected blood donors, and 32 healthy laboratory and clinical personnel were all negative. Also no human T-lymphotropic virus III antibodies were detected in sera of 187 prostitutes in the Munich area.

Acquired Immunodeficiency Syndrome↗

Antigens and circulating immune complexes related to the primate retroviral glycoprotein SiSVgp70. Indicators of early mortality in human acute leukemias and chronic myelogenous leukemias in blast crisis.

Human sera contain antigens and also circulating immune complexes that are related to the primate retroviral envelope glycoprotein gp70 of simian sarcoma/simian sarcoma associated virus (SiSV) and of gibbon ape leukemia virus (GaLV). SiSVgp70 related antigens (AG) and immune complexes (IC) are detected both in leukemic and in nonleukemic sera. In a further analysis of these data, the prognostic significance of SiSVgp70 related AG and IC in leukemic patients was examined. The data show that the presence of SiSVgp70 related AG and IC indicates an unfavorable clinical course and a shorter survival time in acute leukemias (AL) and in chronic myelogenous leukemia in blast crisis (CML-BC). Survival data of 56 of 64 patients tested were analyzed (38 patients with AL and 18 patients with CML-BC). Patients with AL whose sera were positive for SiSVgp70 related AG and IC had a median survival time of 9.5 months after diagnosis versus 16 months for patients negative for such AG and IC. This difference in survival time was more pronounced for patients with acute nonlymphocytic leukemia (ANLL) (6.5 versus 19 months). The difference in survival between SiSVgp70 related AG- and IC-negative and positive groups as tested by life table analysis (log-rank test) is significant (P less than 0.05). Patients with AL of the AG- and/or IC-positive group had fewer complete remissions. Patients who had no remissions belong to the AG- and/or IC-positive group (P = 0.06). Patients with CML-BC whose sera were positive for SiSVgp70 related AG and/or IC had a median survival time of 2 months after diagnosis versus 7 months for patients with sera negative for such AG and IC. As tested by log-rank test, survival curves between the two groups are significantly different (P less than 0.05). These findings suggest that SiSVgp70 related AG and IC may play an important role in the course of acute leukemia and can provide useful prognostic information.

Acute Disease↗

[Arthropathy as an early symptom of hemochromatosis. Overview of the literature and 7 case reports].

In seven patients with hemochromatosis, arthropathy was an early symptom, or first clinical symptom, of the hemochromatosis. In all seven patients, serum iron, transferrin saturation, and parameters of storage iron (serum ferritin, Desferal-test) were clearly elevated. In 5 patients hemochromatosis was associated with the HLA loci A3 and B7. Bone scan proved a sensitive detection method for hemochromatosis arthropathy. In one case joint involvement was detected by bone scan prior to clinical symptoms. Parameters of iron metabolism correlated well with other organ manifestations of hemochromatosis. In contrast, joint involvement did not correlate with parameters of iron metabolism or severity of hemosiderosis of other organs, and was not relieved by phlebotomy. These 7 cases confirm that joint symptoms can be an early or leading symptom of hemochromatosis, can lead to early therapy and thereby prevent major organ damage. It remains undecided, however, whether the arthropathy is a consequence of iron storage or an independent disease which is genetically associated with hemochromatosis.

Female↗

Relapsing acute febrile neutrophilic dermatosis and essential thrombocythemia.

Relapsing acute febrile neutrophilic dermatosis ( AFND ) is reported in a patient with essential thrombocythemia representing the first case of this kind described in the literature. The patient presented with fever, malaise, neutrophilic leukocytosis, dysproteinemia, and coalescing bluish-red painful plaques and papules at palms, forehead, lid, forearm, and thigh. There was a dramatic response to steroids, or indomethacin, with no scarring. AFND was preceded by sore throat and an upper respiratory infection and was accompanied by conjunctivitis and arthritis of knees and ankle-joint. The association of AFND with essential thrombocythemia and with other neoplastic disorders is discussed.

Dermatitis↗

RNA-tumorviruses, oncogenes, and their possible role in human carcinogenesis.

The detection and characterization of oncogenes via RNA tumor viruses (or retroviruses) and the recognition of their location at breakpoints of chromosomal translocations which are frequently found in certain human neoplasms has promoted present understanding of molecular mechanisms underlying carcinogenesis. Oncogenes are cellular genes which can be transduced by RNA tumorviruses and induce malignant transformation under experimental conditions in vivo and in vitro. A role of retroviruses in human leukemogenesis is suggested by epidemiological observations and by the isolation of such viruses from several human T-cell leukemias and lymphomas (human T-cell leukemia/lymphoma virus or HTLV) as well as by biochemical association of retroviral markers with human leukemias. A role of HTLV has been suggested also in a human immune deficiency syndrome (AIDS). In view of the well known role of many factors in carcinogenesis the concept of carcinogenesis as a multistep process as well as the concept of cocarcinogenesis and the role of cofactors other than viruses, such as radiation and chemicals, aging, hormones, graft vs host reaction, environmental factors etc., will have to be carefully considered.

Acquired Immunodeficiency Syndrome↗

Idiopathic refractory sideroachrestic anemia (IRSA) progressing to acute mixed lymphoblastic-myelomonoblastic leukemia. Case report and review of the literature.

A longitudinal observation of a patient with idiopathic refractory sideroachrestic anemia (IRSA) progressing to acute mixed lymphoblastic-myelomonoblastic leukemia is reported. The leukemia was characterized by morphology, immunological cell markers, and dissociated clinical responsiveness to vincristine/prednisone and arabinosylcytosine/6-thioguanine. Attention is paid to the hematological changes prior to leukemia development. Acute leukemia was best heralded in this patient by a severe deterioration of dyserythropoiesis and by an increase of blasts in the marrow to more than 5%. The observed preleukemic features are compared to those described in the literature.

Aged↗

Detection and biochemical characterization of antigens in human leukemic sera that cross-react with primate C-type viral proteins (Mr 30,000).

Antigens have been detected in 35 to 40% of sera from patients with leukemia that cross-react with the Mr 30,000 core proteins (p30) of baboon endogenous virus (BaEV) and/or of simian sarcoma-simian sarcoma-associated virus (SiSV) in a solid-phase enzyme immunoassay using anti-SiSV p30 and anti-BaEV p30 antisera. These antigens could not be found in sera from nonleukemic persons. Fetal calf serum; normal chicken, goat, rabbit, and rhesus sera; and normal human serum components like albumin, immunoglobulins, and transferrin did not react with the anti-SiSV p30 and anti-BaEV p30 antisera. The reactivity in the leukemic sera was abolished by treatment with protease, but not with glycosidases. The antigens purified by immunoaffinity chromatography showed essentially one band with an apparent molecular weight of 70,000 on sodium dodecyl sulfate: polyacrylamide gel electrophoresis. In competition enzyme-linked immunosorbent assays the leukemia-associated antigens competed out SiSV p30 in the anti-SiSV p30 system. Peptide mapping experiments with antigens from sera of two different leukemic patients showed that the two antigens were identical concerning numbers of peptides and their position. Eleven of 21 major peptides of SiSV p30 and 10 of 20 major peptides of BaEV p30 (50 to 60% of major peptides) showed mobilities identical with those of the major peptides of the human antigens. The data suggest the presence in human sera of retroviral antigens closely associated with leukemia.

Animals↗

Detection of group and interspecies reactivities of mammalian C-type virus p30 proteins by an enzyme-linked immunosorbent assay (ELISA): enhancement of interspecies reactivity by denaturation.

The applicability of the enzyme immunoassay technique to the detection of group and interspecies determinants of C-type retroviral proteins was tested. For this purpose four groups of C-type retroviruses (MuLV, FeLV, SiSV/GaLV, and BaEV/RD114) were assayed for group-specific and interspecies reactivities of their p30 proteins by an enzyme-linked immunosorbent assay (ELISA). We found that the ELISA can detect group-specific as well as interspecies determinants with sensitivity and reproducibility in purified p30 proteins, disrupted viruses, and cell extracts if an anti-p30 interspecies antiserum is used. If monospecific antisera against MuLV p30, SiSV p30, or BaEV p30 were used, only group-specific reactivities were detected reproducibly, whereas the detectability of interspecies determinants depended on the antisera used and varied even with the same antisera. In assays in which the reactivity of native and denatured p30 proteins was compared the detectability of sodium dodecyl sulphate-denatured MuLV p30 was better than that of native MuLV p30 suggesting that some of the most broadly cross-reactive sequences are localized inside the protein molecule and are freed by the denaturation process. Antisera raised against native and denatured p30 proteins showed identical spectra of reactivity.

Antigens, Viral↗