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Biomedical subjects

H Kuhn

Publications and source records attributed to H Kuhn.

At least 73 records · Page 4Linked to original sources
PubMed1996

Orthotopic implantation of inflamed synovial tissue from RA patients induces a characteristic arthritis in immunodeficient (SCID) mice.

The objective of this work was to study in more detail the human/murine SCID arthritis model with special emphasis on characteristic features initiated by rheumatoid arthritis (RA) synovial membrane (SM) as compared to appropriate control tissues. Small tissue samples from RA-SM, healthy lymph node, healthy SM, and granulomatous tissue of human origin were implanted into the left knee joint of mice with severe combined immunodeficiency (SCID), and the joints were analysed histologically after 7 days. In addition, a time course study, including non-invasive monitoring by serological parameters (human IgM, IgG, and IL-6) and Tc-99m-scintigraphy, was performed for up to 4 weeks on RA-SM recipients. All tissue implants induced transient exudative joint inflammation while RA-SM initiated a characteristic arthritis with pannus tissue of high cellular density, erosion, multinuclear giant cells, lining cell hyperplasia, fibroblast-like cell layers, chondroideal metaplasia, and fibrin deposits. Significantly elevated levels of human immunoglobulin and characteristic signs of chronic inflammation persisted for more than 4 weeks. We conclude that the hu/mu SCID arthritis with RA-SM implants comprises features of non-specific inflammation which is also transiently seen with control tissues but develops characteristic features of chronic RA-like synovitis thereafter.

Animals↗
PubMed1996

Oxygenation of biomembranes by mammalian lipoxygenases: the role of ubiquinone.

15-Lipoxygenase is implicated in the selective breakdown of mitochondria during red cell maturation by virtue of its capability of directly oxygenating phospholipids. To address the reason of the selectivity for mitochondria, we studied the reaction of pure rabbit 15-lipoxygenase with beef heart submitochondrial particles in vitro. This reaction is characterised by a loss of polyenoic fatty acids, the formation of phospholipid-bound hydroperoxy- and keto-polyenoic fatty acids, and oxidative modification of membrane proteins. The total oxygen uptake exceeds the formation of oxygenated polyenoic fatty acids several times. The excessive oxygen uptake was not inhibited by 3,5-di-tert-butyl-4-hydroxytoluene or by respiratory inhibitors, but was partly suppressed by superoxide dismutase plus catalase, salicylate, or mannitol. Pentane-extraction of the submitochondrial particles abolished the excessive oxygen uptake, whereas reconstitution with ubiquinone- 50 restored it. A marked excessive oxygen uptake did not occur during the analogous reaction with erythrocyte ghosts. It is proposed that ubiquinone-50 triggers the formation of hydroxyl radicals from 15-lipoxygenase-derived hydroperoxy-lipids via a Fenton-type reaction driven by ubisemiquinone radicals. A new prooxidative function of ubiquinone in the biologically programmed degradation of mitochondria in certain types of cells is proposed.

Amino Acids↗
PubMed1995

Mechanism of inhibition of neointimal formation by the angiotensin-converting enzyme inhibitor cilazapril. A study in balloon catheter-injured rat carotid arteries.

We investigated the mechanism of inhibition of neointima formation by the angiotensin-covering enzyme the carotid artery. We looked for the effects of cilazapril on all phases of the response to injury, ie, on proliferation of smooth muscle cells (SMCs) in the media, their migration, their proliferation in the neointima, and their disposition of extracellular matrix in the neointima. Although treatment was discontinued after 2 weeks, the inhibitory effect of cilazapril on neointimal formation was evident even 52 weeks after injury. The amount of extracellular matrix deposited in the intima during cilazapril treatment was decreased by 20% 2 weeks after injury, but no effect was seen if tissues were analyzed at 4 or 52 weeks. [3H]Thymidine-labeled cells (pulse labeling as well as 14-day continuous labeling) showed a decrease in SMC labeling in the tunica medica by 50%, but no inhibition in the labeling indices was seen in the neointima. The fraction of unlabeled neointimal cells in the cilazapril-treated rats as judged from continuous labeling experiments was inhibited by 86%. Taken together, these data suggest an antiproliferative effect on medial SMCs and an inhibition of SMC migration into the intima by cilazapril. Since intimal extracellular matrix deposition was only delayed, the decrease in medial SMC proliferation and subsequent migration seems to be the main reason for the reduction of neointima formation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

[Hypertrophic non-obstructive cardiomyopathy in rigid spine syndrome].

A case report is given of a 37-year-old patient suffering from rigid spine syndrome and hypertrophic non-obstructive cardiomyopathy. Clinical-cardiological and neurological findings are discussed. This is the first description of such a case in the German-language region; only two other similar publications are found in the whole literature. Follow-up is documented over a period of 10 years; apart from the early dominating neuro-muscular deficit, we saw only a mild progression of symptoms. Signs of an increasing diastolic dysfunction of the left ventricle without clinical complaints were the main cardiological findings. Because of substantial progress in elucidating the genetics of hypertrophic cardiomyopathies over recent years, case reports about the association of two different type of muscular disorders are thought to be of special interest in terms of a common etiological basis.

Adult↗
PubMed1994

On the origin of the genetic code.

A series of stages in the evolution of the genetic code is postulated, representing a chain of logical steps that leads to the present-day code. The stages described are based on translation machinery between the RNA world and that of amino acids, a model that consists of an RNA assembler strand along which RNA hairpin molecules are lined up, forming a picket-fence-like aggregate. Each hairpin carries an amino acid at the bottom of one of its legs, and the mutual proximity of amino acids achieved in this way facilitates their linkage into oligopeptides, in a sequence governed by the nucleotide sequence along the assembler strand, the code. The order in which amino acids are introduced into the code is in the approximate order of their availability, tempered by polarity and structural considerations.

Amino Acid Sequence↗
PubMed1994

The integrin alpha IIb-beta 3, platelet glycoprotein IIb-IIIa, can form a functionally active heterodimer complex without the cysteine-rich repeats of the beta 3 subunit.

Integrin alpha IIb-beta 3 binds fibrinogen via the recognition sequence Arg-Gly-Asp-Ser (RGDS). We have used the baculovirus/insect cell expression system to study the structural requirements for the formation of a functionally active fragment of alpha IIb-beta 3. A tandem baculovirus transfer vector was constructed containing the cDNA coding for the heavy chain of human alpha IIb (alpha IIbH, amino acids 1-874) and the cDNA coding for a truncated form of human beta 3 (t beta 3; amino acids 1-469). Sf9 insect cells were infected with the corresponding baculovirus, and the produced soluble recombinant proteins were purified using an RGD-like affinity column. The bound receptor fragments were specifically eluted with RGDS and existed as a heterodimeric complex (rec alpha IIbH-t beta 3) with an apparent M(r) of 160,000. In an immunocapture assay, the monoclonal antibody pl-55, which only recognizes the functionally active form of alpha IIb-beta 3, bound to the purified complex. Rec alpha IIbH-t beta 3 specifically bound 125I-fibrinogen with an affinity comparable with that of purified platelet alpha IIb-beta 3. Electron micrographs of rotary-shadowed rec alpha IIbH-t beta 3 showed that the complex had the characteristic globular head, but the two rodlike tails were 4-6 nm shorter than those found in intact alpha IIb-beta 3. Thus, the cysteine-rich repeats of beta 3 are not required for assembly, stability, and functional activity of this integrin.

Amino Acid Sequence↗