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S Hofer

Publications and source records attributed to S Hofer.

47 records · Page 3Linked to original sources
PubMed1993

Regulation of the L-arginine-dependent and tetrahydrobiopterin-dependent biosynthesis of nitric oxide in murine macrophages.

Nitric oxide is a recently discovered biomolecule with a broad range of actions. The present study investigated the regulation of nitric oxide synthase activity by dexamethasone and the cofactor tetrahydrobiopterin in murine macrophages. The influence of the tetrahydrobiopterin biosynthesis inhibitors 2,4-diamino-6-hydroxypyrimidine, an inhibitor of GTP cyclohydrolase I, and phenprocoumon, an inhibitor of sepiapterin reductase, on the synthesis of nitric oxide was investigated. Dexamethasone decreased the nitric oxide production due to direct inhibition of the induction of nitric oxide synthase and of GTP cyclohydrolase. Substitution of tetrahydrobiopterin via sepiapterin could not overcome the dexamethasone-mediated inhibition. 2,4-Diamino-6-hydroxypyrimidine abolished nitric oxide synthesis and synergized with dexamethasone, completely eliminating nitric oxide production. Phenprocoumon inhibited production of nitric oxide via interference with later steps of tetrahydrobiopterin biosynthesis. An exogenous supply of tetrahydrobiopterin through sepiapterin led to a further increase of nitric oxide production, even in fully activated macrophages. The amount of nitric oxide produced by murine macrophages is therefore limited by the amount of tetrahydrobiopterin present in the cells. Inhibitors of tetrahydrobiopterin biosynthesis could provide a novel approach for therapy of pathological conditions mediated by nitric oxide, such as septic shock.

Alcohol Oxidoreductases↗
PubMed1993

Nitric oxide synthase is not a constituent of the antimicrobial armature of human mononuclear phagocytes.

Nitric oxide synthase (NOS) has received immense interest as an antimicrobial and antitumoral effector system of mononuclear phagocytes from rodents. Because there is increasing doubt that an analogous system exists in human macrophages, NOS was reexamined in these cells. Under tightly controlled conditions, with murine macrophages as positive controls, human macrophages failed to secrete nitric oxide (< 0.1 mumol/10(6) cells/24 h), even after activation with endotoxin, interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, bacteria, or proliferating lymphocytes. The discrepancy between murine and human macrophages depended on neither the anatomic source (blood, peritoneum), the agent used for activation, nor the duration of activation. NOS activity was paralleled by metabolization of L-arginine to L-citrulline. Exogenous tetrahydrobiopterin, an essential cofactor of NOS not synthesized by human macrophages, did not support NOS activity in human macrophages. Also, no NOS activity was found in cellular subfractions of human macrophages. It appears that in humans, the inducible high-output NOS is not conserved as an antimicrobial system of macrophages.

Amino Acid Oxidoreductases↗
PubMed1989

[Combined GM-CSF and erythropoietin therapy in myelodysplastic syndrome].

A 60-year-old patient with a myelodysplastic syndrome (MDS) corresponding to refractory anemia with an increase in blast cells (RAEB) was treated with granulocyte-macrophage colony stimulating factor (GM-CSF) and erythropoietin (EPO) for severe symptomatic pancytopenia. During the GM-CSF treatment a distinct increase in granulocytes was observed, but the reticulocytes and thrombocytes decreased to the point where treatment had to be discontinued after eight days. After subsequent treatment with EPO the reticulocyte count rose from 0% to 2%. However, this rise alone was insufficient to decrease the number of blood transfusions required. The thrombocyte count rose to the original values after the cessation of GM-CSF therapy while continuing treatment with EPO. Bone marrow investigations were performed before and after GM-CSF treatment and indicated a distinct increase in the myeloid precursor cells after therapy, without an increase in blasts. On the other hand, an obvious decrease in erythro- and megakaryopoiesis was observed.

Anemia, Refractory, with Excess of Blasts↗
PubMed1984

Synthesis of bovine growth hormone by Streptomyces lividans.

Streptomyces lividans 66 was transformed with a plasmid containing the regulatory region of the Streptomyces fradiae aph gene and a structural gene that specifies bovine growth hormone (bGH). When grown in liquid culture the transformant contained a protein identical to authentic bGH, as judged by radioimmunoassay and immuno-blotting (Western analysis). The bGH was present in cells that had been in culture for up to four weeks but was not found in the medium. The strategy employed should be generally applicable to the expression of foreign genes in actinomycetes.

Animals↗
PubMed1983

[Initial results with the dynamic hip screw in comparison to other osteosynthesis procedures].

30 fractures of the proximal end of the femur were stabilised with so-called "dynamic hip screws" (AO/ASIF). This method seems to be more suitable for some inter-trochanteric fractures which pose problems questioning our usual treatment with Ender's elastic round nails. The dynamic hip screw system is also more stable for femoral neck fractures of type Pauwels III than 4 cancellous bone screws. One phenomenon which can not yet be fully explained is the slipping out of the screw to an extent unobserved in other procedures.

Adult↗
PubMedDate not supplied

How strong is the evidence for mediational hypotheses of age-related memory loss? Commentary.

BACKGROUND: Luszcz and Bryan review research supporting three theories of age-related memory loss: the speed hypothesis, the executive function hypothesis, and the common cause hypothesis. OBJECTIVE: The aim of this commentary is to extend that review by encouraging consideration of the strength (or lack thereof) of the empirical evidence supporting theories of age-related memory loss. METHODS: Arguments are presented that call into the question the strength of the evidence that derives from cross-sectional analysis of individual difference sources of variance. RESULTS: Supporting evidence for mediational hypotheses of cognitive aging (1) derives from potentially ambiguous statistical techniques; (2) is based on untested assumptions about the between and within person sources of variance; (3) is not supported by longitudinal studies, and (4) relies heavily on arguments of parsimony. CONCLUSIONS: Existing evidence is not strong enough to grant any particular theory presumptive status. We concur with Luszcz and Bryan that supplementing the now popular individual differences research designs with alternative approaches would advance theory development and testing.

Aging↗