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Biomedical subjects

E Hahn

Publications and source records attributed to E Hahn.

At least 73 records · Page 4Linked to original sources

Occupational acroosteolysis in vinyl chloride workers in Israel.

Exposure to vinyl chloride monomer (VCM) may result in a bizarre syndrome, which is characterized by lytic changes in the distal phalanges, cutaneous stigmata of scleroderma, and Raynaud's phenomenon. Detailed case histories of two such patients are presented. Epidemiologic, pathogenetic and radiological aspects of occupational acroosteolysis are briefly reviewed. The possibility is emphasized that the condition may result not only from industrial (i.e., occupational) exposure to VCM but also from exposure in the home or neighborhood (i.e., nonoccupational).

Adult↗

Levamisole-induced immunostimulation in spondylarthropathies.

The term "seronegative spondylarthritis" (S.S.A.) has been assigned to rheumatic disorders with closely related clinical features, defined by seronegativity and HLA-B27 phenotype. Its pathogenesis may be linked with a genetically controlled defective immune response. Therefore, 37 men with S.S.A. were treated with levamisole (150 mg/day, 3 days/wk) to stimulate the immune reactions. In a randomised controlled crossover study these patients also received a placebo; each period ran for 12 wk. Symptomatic therapy was continued through the entire 6 mo. Serious side-effects led to withdrawal of the active drug in 9 patients. Clinical response was measured in terms of a cumulative joint index, spondylometry, morning stiffness, and a pain scale. Treatment with levamisole resulted in a significant improvement in these parameters. Radiological evidence of sacroiliitis was present in 48.6% before and after levamisole, and joint scanning with 99Tc-pyrophosphate also revealed no progress in the disease. After levamisole treatment, IgM levels fell significantly (P less than 0-014). Likewise, the previously high percentage of antibodies with weak cytotoxic activity against lymphocytes was reduced after levamisole (P less than 0-049), and an increased rate of leucocyte-migration inhibition (L.M.I) was found in the levamisole-treated group. Thus, the immunostimulating properties of levamisole may interfere with defective immunoregulation in S.S.A. and, by improving the clinical conditions, lead to a change in the course of this disease.

Adult↗

[Clinical study of the biological availability of lanatoside C and digoxin in long-term tests].

The bioavailability of digoxin and lanatoside C from tablets and dragees and from solutions of the two substances has been investigated intraindividually in patients on maintenance therapy. Plasma levels and urinary excretion were analyzed by radioimmunoassay. Both plasma concentrations and urinary excretion were significantly higher after digoxin tablets (1.5+/-0.17 ng/ml; 0.15 mg/24 h) than after lanatoside C dragees (0.98+/-0.15 ng/ml; 0.1 mg/24 h). When equimolar solutions of both drugs, corresponding to 0.5 mg digoxin, were given, plasma concentrations and urinary excretion after digoxin (1.6+/-0.08 ng/ml; 0.14 mg/24 h) were again significantly higher than after lanatoside C (1.18+/-0.09 ng/ml; 0.1 mg/24 h). These results suggest that while the absorption of lanatoside C is lower than that of digoxin, it is better than has been generally assummed. The variability in the absorption of lanatoside C between patients is no greater than with digoxin.

Adolescent↗

[Lymphocyte antigens in autoimmune thrombocytopenia].

18 patients with proven autoimmune thrombocytopenic purpura (ATP) (group A) were screened for human lymphocyte antigens (HLA) and compared with 13 patients with secondary thrombocytopenic purpura (group B). An additional comparison was made with a control panel of a European population (group C). HLA-B8 was present in 12 of 18 patients (66.6%) of group A, compared with only one of 13 patients (7.6%) of group B. HLA-B12 occured in 8 of 18 patients (44.4%) of group A, compared with, again, only one of 13 patients in group B. The alleles HLA-B8/B12 were observed in 7 of 18 patients (38.8%) of group A, whereas no patient of group B exhibited such phenotypes. The differences were statistically significant (p less than 0.001 to p less than 0.03). A high incidence of the antigens HLA-B8/B12 has been noted in a family of which three members displayed serious symptoms of ATP over three generations. Thus, it is conceivable that individuals who carry the HLA-B8/B12 alleles run an increased risk of developing the disease if they are exposed to additional causal factors which finally trigger ATP.

Adolescent↗

Requirement for T cells in the antibody response of mice to calf skin collagen.

The antibody response to triple-helical calf skin collagen is apparently regulated by T cells since nude mice (BALB/c strain) responded to this antigen only after transfer of T cells. Syngeneic transfer of B and T cells was required to prepare thymectomized and irradiated normal C57B1/10 recipients for an anti-collagen response. Reconstitution by B cells alone was unsuccessful. The results are compatible with previous evidence on the H-2 linked genetic control of the antibody response to and the non-repetitious nature of helical antigenic determinants in calf collagen.

Animals↗

Visualization of type I and II collagens in tissue sections by immunohistologic techniques.

Rabbit and rat antibodies were prepared against Type I and II collagens derived from bovine skin and articular cartilage, respectively. As judged by passive hemagglutination and radioimmune assays, these antibodies could be rendered generally specific for the type of collagen used for immunization by immunoadsorption. Thus, antibodies to Type II collagen did not cross-react with Type I and III collagens from skin. However, antibodies to Type I collagen still showed some cross-reaction with Type III collagen. Antibodies to Type I procollagen showed a negligible degree of cross-reaction with Type III procollagen. These purified antibodies reacted strongly with bovine and human tissue collagen as demonstrated by indirect immunoflourescence. Antibodies to Type I collagen stained dermal tissue, perichondral tissue, kidney stroma, aortic tissue, and annulus fibrosus. Antibodies to Type II collagen stained mainly the hyaline matrix of rib cartilage and nucleus pulposus. The staining patterns with anti-Type I procollagen were similar but not identical to that found with antibodies to Type I collagen. Neither of these antibodies reacted with kidney glomerular basement membrane. These antibody reagents are recommended as a sensitive and rapid screening tool for studying tissue distribution of collagen under normal and pathologic conditions.

Animals↗

[Comparison of digitoxin bioavailability from tablets and elixir during maintenance therapy (author's transl)].

The bioavalability of digoxin tablets and solution has been studied during maintenance therapy in a cross over study. Each preparation was given over a period of at least 7 days to patients with compensated congestive heart failure. Urine concentrations and plasma levels were analysed for digitoxin. There was no significant difference between the two preparations. Determination of steady state serum concentrations and urinary excretion during maintenance therapy as an index of bioavalability are more cumbersome than a single dose study. From a pharmacokinetic point of view however, analyses of steady-state conditions are preferable to a single dose study. In addition, steady state of drug input and output resembles the usual digitalis therapy.

Administration, Oral↗

Antigenic determinants in the disulfide regions of bovine fibrinogen.

Rabbit antibodies to bovine fibrinogen were used to study the antigenic activity of four cyanogen bromide peptides containing the disulfide regions of this molecule. In precipitation tests the highest activity was associated with the peptide F-CB3 which is exclusively derived from the alpha-chain. Reduction of the single disulfide bridge in peptide F-CB3 did not influence its serologic activity. Weaker reactions were observed with the N-terminal multichain peptide F-CB1. The antigenicity of peptide F-CB1 was not affected by removal of fibrinopeptides A and B but it was lost after reduction. The immunological activity of the multichain peptide F-CB2 was even less than that of peptide F-CB1 and the antigenic determinants were destroyed by reduction. A large fragment essentially composed of peptides F-CB1 and F-CB2 could be obtained by limited cyanogen bromide cleavage and showed considerably better immunological activity than peptides F-CB1 and F-CB2 together. Apparently no activity was associated with a mixture of small hydrophobic, disulfide-loop peptides tentatively called peptide F-CB4. The large loss of antigenic activity in cyanogen bromide digests of fibrinogen suggests that the disulfide-stabilized regions do not have an important role in maintaining conformational antigenic determinants of fibroinogen. Changes in noncovalently stabilized conformation requiring uncleaved chains is considered as a possible reason for the findings observed.

Amino Acids↗

H-2-linked genetic control of antibody response to soluble calf skin collagen in mice.

An autosomal dominant immune response gene could be demonstrated in congenic resistant strains of mice which is linked to the H-2 locus and controls the antibody response to soluble calf collagen. High responsiveness was associated with the H-2 alleles, b and f, low responsiveness with the H-2 alleles, d, k, m and r. Studies with calf procollagen, which contains an additional carrier moiety, indicated that these genetic differences might be expressed at the level of T cells.

Animals↗

Demonstration of a unique antigenic specificity for the collagen alpha1 (II) chain from cartilaginous tissue.

The rabbit antibody response to native collagen (chain composition [alpha1(II)3) from cartilaginous tissue, has been examined by agglutination assays, gel diffusion, haemagglutination-inhibition studies, and immunoadsorption. The results show that the rabbit antibody response to the cartilage-type collagen is characterized by considerable reactivity to both helical [alpha1(II)]3 as well as alpha1(II) chains. This is in contrast to the rat antibody response to the same antigens where titres are generated to largely helical antigenic determinants. Similarly to the rat response, rabbit antibodies to [alpha(II)]3 exhibit no strong cross-reaction with the genetically distinct [alpha(I)]2ALPHA2 collagen or its component chains. Strong cross-reactions were, however, observed between bovine and chick alpha1(II) chains. One of the major antigenic sites on [alpha1(II)]3 collagen appears to reside in the sequence represented by CB-11, a peptide derived from the helical portion of the [alpha1(II)]3 molecule after cyanogen bromide cleavage. The data, however, are compatible with the presence of other antigenic determinants which are probably located in the amino- and carbocy-terminal portions of the molecule.

Agglutination Tests↗

Specificity of the antibody response in inbred mice to bovine type I and type II collagen.

Mouse antibodies to soluble bovine skin (type I) collagen react with determinants which are located in the rigid triple-helical portion of the antigen and become destroyed upon unfolding the molecule. Helical antigenic determinants are dependent on the genuine chain assembly, e.g. alpha[1(I)]2alpha2. Artefactual triplehelical structures of the composition [alpha1(I)]3 or [alpha2]3 or a genetically distinct type II collagen from cartilage showed no or only weak cross-reactivity. Pepsin treatment of type I collagen known to remove short, non-helical sequences at both ends of the molecule had virtually no effect on antigenicity and immunogenic activity. A radioimmunoassay failed to detect antibodies in three congenic resistant mouse strains immunized with denatured type I collagen. These strains had been previously classified as high or low responders to native type I collagen. Agglutination titres vs denatured collagen culd already be demonstrated in nonimmune sera. The agglutinating activity was labile against heating at 56 degrees and could not be increased by immunization. Two out of five inbred strains showed a high response against pepsin-dissolved bovine type II collagen with the chain composition [alpha1(II)]3. Lack of correlation in the responder state to both collagen types indicated control by different immune response genes. Antibodies to type II collagen also reacted against triple-helical antigenic determinants and showed neglible cross-reaction with type I collagen.

Animals↗