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Biomedical subjects

H Wagner

Publications and source records attributed to H Wagner.

At least 487 records · Page 27Linked to original sources
PubMed1986

Structural analysis of an RNA molecule involved in replication control of plasmid R1.

The replication control circuit of the FII plasmids R1, R100 and R6-5 involves a small untranslated RNA molecule of about 93 nucleotides. This RNA, designated CopA RNA in plasmid R1, acts in vivo as a post-transcriptional inhibitor of the expression of the RepA protein whose synthesis is required for each round of plasmid replication. We have studied the structure of CopA RNA in solution by probing with single-strand- as well as double-strand-specific nucleases. Our data show that CopA RNA has two stem-loop structures connected by a long spacer region and a single-stranded 3'-tail. Enzyme reactions were performed under buffer conditions where we find strong and specific binding of CopA RNA to its target RNA (to be published elsewhere), and the patterns were compared to digests in two other buffer systems. All partial cleavages supported the proposed secondary structure. We also analyzed the stem-loop regions of CopA RNAs from two R1 copy number mutants. The data show that both RNAs have altered loop structures. The implications of these findings are discussed.

DNA Replication↗
PubMed1986

[Amiodarone therapy--behavior of serum and fatty tissue concentrations].

Thirty-eight patients with refractory supraventricular and ventricular tachyarrhythmias were administered a mean oral dosage of 400 mg amiodarone daily (200-600 mg). A high-pressure liquid chromatography method was used to measure serum concentrations of amiodarone and its metabolite desethylamiodarone after one week, one month, three months, and then at 6-month intervals. In 24 patients subcutaneous fatty tissue concentrations were also measured. The mean follow-up was 9 months (4 days to 29 months). A linear correlation was found between amiodarone and its metabolite in serum (r = 0.56, p less than 0.001) as well as in subcutaneous fatty tissue (r = 0.67, p less than 0.001). While serum concentrations were dose dependent, tissue concentrations accumulated during chronic therapy (p less than 0.01, both). Clinical efficacy was achieved in 84% of the patients. No statistically significant difference was found between responders and non-responders as regards serum and subcutaneous fatty tissue concentrations. Side effects of amiodarone occurred in 63%. The incidence of adverse effects was related to significantly higher serum and subcutaneous fatty tissue concentrations of amiodarone and its metabolite (p less than 0.001, both). Thus, although the determination of serum and subcutaneous fatty tissue concentrations does not seem to be helpful for assessing clinical efficacy of this antiarrhythmic drug, these values may predict the occurrence of adverse effects.

Adipose Tissue↗
PubMed1986

Function of the CD4 and CD8 molecules on human cytotoxic T lymphocytes: regulation of T cell triggering.

The function of the T cell differentiation antigens CD4 (Leu-3/T4) and CD8 (Leu-2/T8) on human cytotoxic T lymphocytes (CTL) is presently seen only in conjugate formation between CTL and target cell via class II or class I MHC antigens rather than in the later killing steps. In this study, human CD4+ and CD8+ CTL clones were used to investigate the effects of monoclonal antibodies against these differentiation antigens on nonspecific triggering of cytotoxicity. Cytotoxicity was induced either by antibodies against the CD3 (T3) antigen or by the lectins Con A and PHA. Anti-CD4 or anti-CD8 antibodies specifically inhibited all types of cytotoxicity of CD4+ or CD8+ CTL, respectively, regardless of the specificity of the CTL for class I or class II HLA antigens and regardless of whether target cells expressed class I or class II antigens. These results are incompatible with an exclusive role of the CD4 and CD8 molecules in MHC class recognition and are discussed with respect to a function as negative signal receptors for these molecules on CTL.

Antibodies, Monoclonal↗
PubMed1986

Detection of rearranged T cell receptor beta-chain gene and induction of cytolytic function in interleukin 2-responsive day 14-15 murine fetal thymocytes.

A subpopulation of interleukin 2 (IL 2) receptor-positive day 14-15 murine fetal thymocytes can be induced by recombinant IL 2 to proliferate over prolonged time periods in dissociated cell cultures. The proliferating day 14-15 fetal thymocytes exhibit no cytolytic effector function, nor do they rearrange T cell receptor beta chain genes. This contrasts with thymic organ cultures in which day 14-15 thymocytes do rearrange beta chain genes and give rise to immunocompetent cells. However, such events can also take place in dissociated cell cultures, provided the IL 2-responsive thymocytes are cultured on syngeneic feeder cells in the presence of IL 2 and the mitogen concanavalin A. Under such conditions rearrangement of the beta chain gene complex becomes detectable and cytolytic effector cells are generated. The frequency of inducible cytolytic precursor cells in day 14-15 thymocytes is 1/7000. These data either imply that immunocompetent cells are already present in the day 14-15 fetal thymus, or differentiation from precursors to immunocompetent cells must occur in dissociated cell cultures.

Animals↗
PubMed1986

[Indications for corrective operations for maintaining function in post-traumatic deformities of the distal lower leg and foot].

Reconstruction surgery in posttraumatic deformities in the lower leg and the foot is indicated under different aspects: restoration of function, improvement of prognosis, improvement of function and melioration of physical appearance. Technically effective surgical means are available to date, such as: metaphyseal closing and opening wedge osteotomies, diaphyseal step-cut osteotomies, diaphyseal and metaphyseal displacement osteotomies, lengthening osteotomy, external fixation, revision of infections, joint revisions, scar revisions, nerve revisions, plastic skin operations.

Foot Deformities, Acquired↗
PubMed1986

A human lymphokine released by mononuclear blood cells upon contact with CEA.

As revealed by the macrophage electrophoretic mobility (MEM) technique mononuclear blood cells from certain cancer patients respond to carcinoembryonic antigen (CEA). This phenomenon appeared to be due to a specific lymphokine release. In this study, the lymphokine activity of supernatant pools was stepwise enriched by gel filtration on Sephadex. The mediator activity was recovered within a molecular mass region less than 47 kDA. The lymphokine was highly enriched during further gel filtration steps and showed a single activity peak in the molecular mass region of 23.5 kDa. Gel filtrations of appropriate control supernatants resulted in biologically inactive fractions. The lymphokine was heat-labile at 56 degrees C, showed a clear-cut, dose-dependent effect on macrophages, and could be blocked by fucose. Preparative gel electrophoresis of radiolabeled and unlabeled lymphokine resulted in two corresponding peaks of biological activity and radioactivity.

Carcinoembryonic Antigen↗
PubMed1986

Management of vascular complications of bacterial endocarditis.

Peripheral arterial emboli that result from bacterial endocarditis may be silent or catastrophic. Cardiac surgical intervention may prevent embolism, but the guidelines for timing of intervention are unclear. An accepted approach is to intervene only if two episodes of peripheral embolism occur. Our recent experience suggests a more refined approach is in order. Eight children with active bacterial endocarditis have been treated with embolic complications. One patient with abdominal pain and GI bleeding was treated with heparin for multiple peripheral mesenteric emboli. Four patients had femoral embolectomies, one twice. Three patients developed embolomycotic aneurysms of the aorta in two cases and the common iliac in one; all were ruptured and two survived with staged reconstruction in one and extra-anatomic bypass in the other. Staph aureus and Strep viridans were the organisms involved most often. A review of the details of care in these patients leads to the following conclusions: angiographic survey reveals that most patients have multiple emboli; early embolectomy may prevent formation of infected aneurysms; Staph aureus infected patients are at risk for development of infected aneurysms; patients with large floppy vegetations in the left heart on echocardiography are at high risk for embolism; and 2 to 3 weeks from onset of endocarditis is the peak time for embolic risk.

Adolescent↗
PubMed1986

Hepatic regenerative stimulator substance in the rabbit. Relation to liver regeneration after partial hepatectomy.

The occurrence and activity of hepatic regenerative stimulator substance was investigated in the partially hepatectomized rabbit and related to biochemical and morphological parameters of liver regeneration. Male rabbits were 60% hepatectomized by excising the Spigelian, left lateral and left central lobes of the liver leaving the gallbladder in situ. [3H]Thymidine incorporation into DNA, the fraction of labelled hepatocyte nuclei, the fraction of mitoses and thymidine kinase activity rose from basal levels at 30-40 h after hepatectomy and increased up to 12-fold at 40-60 h. After 7 days, proliferation parameters returned to near prae-hepatectomy values and 82% of the initial liver mass was restored. Hepatic regenerative stimulator substance was biologically active when prepared from rabbit livers between 18-30 h after partial hepatectomy. At 12 and 30 h after intraperitoneal injection of the extract into normal rats, hepatic DNA synthesis was stimulated up to 2-fold in a dose-dependent fashion. The biological activity was protease-sensitive and thus depended on a protein component of the extract. The data demonstrate the existence of hepatic regenerative stimulator substance in regenerating rabbit liver and suggest that it is implicated in the regulation of liver growth after partial hepatectomy.

Animals↗
PubMed1986

Exogenous IL2 partially reverts CML non-reactivity acquired during prophylactic immunosuppression with cyclosporin A of human allograft recipients.

Proliferative and cytolytic lymphocyte responses and the influence of exogenous interleukin 2 (IL2) on cell-mediated lympholysis (CML) reactivity were evaluated in 12 allograft recipients. Responses were induced by mitogenic lectins or by donor and third-party cells. Patients were tested immediately before transplantation (Tx) and one and three months after grafting. Prophylactic immunosuppression consisted of Cyclosporin A (CyA) and low-dose prednisone (P). Analysis of post transplant cells revealed a reduced overall proliferative T cell responsiveness induced by both alloantigens and mitogenic lectins. No evidence for donor-specific reduction of MLC responses was seen. Overall CML reactivity of post-Tx lymphocytes was also impaired. This was accompanied by donor-specific CML non-reactivity in six of seven patients with quiescent grafts. In these patients, the cytolytic potential against donor cells could be restored when maximal T cell help via exogenous IL2 was provided.

Adult↗
PubMed1986

Influence of blood-brain barrier opening to proteins on development of post-ischaemic brain injury.

The effect of the BBB opening to proteins on development of post-ischaemic brain injury was assessed in 32 cats subjected to one hour MCA occlusion. The CBF was measured by hydrogen clearance from electrodes inserted in the caudate and the cerebral cortex within the MCA territory. In 16 animals, a prevention of subsequent reactive hyperaemia was attempted by hypovolaemia, produced by withdrawal of blood just before the release of MCA occlusion. The hypovolaemia was successful in prevention of post-ischaemic hyperaemia in five out of eight cats sacrificed at 3 h and in six out of eight animals killed after 3 and 14 days. In cats sacrificed 3 h after release of MCA occlusion, ischaemic sites, associated with reactive hyperaemia, showed evidence of BBB breakdown to proteins and significantly more severe oedema than at the ischaemic sites without reactive hyperaemia, which otherwise failed to reveal leakage of EB tracer. In the cats sacrificed at 3 and 14 days, the ischaemic sites which showed reactive hyperaemia after release of MCA occlusion, revealed much more severe ischaemic brain tissue injury than was observed at the sites without reactive hyperaemia, which also did not show any EB leakage. The present study indicates that reactive hyperaemia, which follows release of major cerebral artery occlusion, may play a significant role in the breakdown of the BBB to proteins, and in increasing the severity of post-ischaemic oedema and of ischaemic brain tissue injury.

Animals↗
PubMed1986

Host-reactive cytotoxic T lymphocyte precursors in long-lived fully allogeneic mouse bone marrow chimeras.

Fully H-2-incompatible chimeric mice were constructed by grafting lethally (950 rad) irradiated germ-free (GF) CBA (H2k) mice with anti-Thy 1 antibody plus complement-treated allogeneic C57Bl/6 (B6) (H2b) bone marrow cells. These chimeric mice were kept for more than 11 months, either under GF conditions or under barrier-sustained specific-pathogen-free (SPF) conditions. Controls included nonirradiated, nontransplanted, sex- and age-matched CBA and B6 mice raised under SPF conditions, and syngeneic chimeric mice of the CBA----CBA type kept under GF and SPF conditions. All chimeric mice were completely repopulated with donor-type lymphoid cells and showed no clinical or histological evidence of graft-versus-host disease. From the fully allogeneic chimeric mice, we enumerated the numbers of splenic cytotoxic T lymphocyte precursors (CTL-p) that could be clonally expanded under limiting dilution conditions in response to third-party alloantigens, or nonmodified and trinitrophenyl (TNP)-modified stimulator cells bearing host or donor H-2 antigens. The existence of high numbers of alloreactive and host- or donor-type H-2-restricted TNP-specific CTL-p in the spleens of fully allogeneic chimeras indicated almost normal immunocompetence. The surprising finding, however, was that large numbers of host (CBA)-reactive splenic CTL-p were inducible under limiting dilution conditions in healthy long-lived allogeneic chimeras, although these chimeric mice were devoid of any histological or clinical signs of graft-versus-host disease.

Animals↗
PubMed1986

Structure and properties of polysaccharides from Viscum album (L.).

Polysaccharides are possibly involved in the pharmacological effects of Viscum album (mistletoe) extracts, which are used in cancer therapy. Therefore the water-soluble polysaccharides of the fresh plant and the fermented proprietary preparation Iscador were isolated and characterized inter alia by methylation analysis, partial hydrolysis and C-13-NMR spectroscopy. The main polysaccharide of the green parts of Viscum is a highly esterified galacturonan whereas in Viscum 'berries' a complex arabinogalactan is predominant. Both types of these constituents were found in Iscador but with definite changes in molecular weight and structure. An interaction between the arabinogalactan and the galactose-specific lectin (ML I) in Viscum could be demonstrated. In three immunological tests (granulocyte, chemiluminescence, carbon clearance test) the polysaccharides failed to increase phagocytic activity of granulocytes and macrophages.

Carbon↗
PubMed1986

Studies on the standardization of mistletoe preparations.

The newly isolated phenylpropanoids syringin, syringenin-apiosylglucoside, eleutheroside E and the high molecular lectins and viscotoxins were selected for a standardization of mistletoe extracts and drug preparation. The phenylpropanoids found in all alcoholic and aqueous extracts were suitable for an HPLC fingerprint analysis, and for quantitative determination. The lectin content of the drug preparations was determined by single radial immunodiffusion. As shown by the isoelectric focussing method, Iscador and fermented mistletoe extracts contain only the mistletoe lectins ML II/III, whereas the proteins of the ML I complex are missing. For identification and quantitative determination of viscotoxins, an HPLC method was designed.

Chromatography, Affinity↗