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M Riederer

Publications and source records attributed to M Riederer.

10 recordsLinked to original sources
PubMed2001

Generation of a humanized, high affinity anti-tissue factor antibody for use as a novel antithrombotic therapeutic.

Blocking the cofactor function of human tissue factor may be beneficial in various coagulation-mediated diseases. The murine antibody D3 binds to the membrane proximal substrate interaction region of human tissue factor and blocks tissue factor function even in the presence of bound factor VIIa. The cloned murine D3 antibody was humanized and affinity matured by exchanging amino acids in the complementarity determining regions as well as in the antibody framework. The humanized antibody, D3H44, bound to tissue factor with a 100-fold increased affinity (KD 0.1 nM) as compared to the original murine and chimeric versions. Depending on the particular disease, different pharmacokinetic properties of the antibody may be required and, therefore, several antibody variants-- F(ab), F(ab')2, IgG2, IgG4 and IgG4b-were generated. In vitro, the humanized D3 antibodies displayed potent inhibition of plasma clotting and tissue factor: factor VIIa-mediated activation of factors IX and X (e.g. D3H44-F(ab')2, IC50(F.X) 47 pM). In addition, D3H44-F(ab')2 completely prevented fibrin deposition in a human ex vivo thrombosis model under venous blood flow conditions (IC50 37 nM). The humanized D3 antibodies may be utilized for treatment of cardiovascular diseases which involve tissue factor activity, e.g. acute coronary syndrome and venous thrombosis.

Amino Acid Sequence↗
PubMed2000

[Quality assessment of multiple trauma management bu ISS, TRISS or ASCOT?].

OBJECTIVES: Scores have been developed to assess the quality of trauma treatment. Our objective was to investigate prospectively whether there is a significant difference between the predicted survival and mortality rates with ISS, TRISS and ASCOT and observed rates in our patients. If the answer is affirmative, we also wished to evaluate whether the difference is significant enough to justify the greater data collection effort required for ASCOT as opposed to TRISS, and for TRISS as opposed to ISS. PATIENTS AND METHODS: Charts from 470 of 484 blunt multiple trauma patients with an ISS of 8 or more documented as part of a National Fund Study between June 1990 and June 1996 were reviewed. We compared the survival and mortality rates calculated by ISS, TRISS and ASCOT with the observed survival and death rates. RESULTS: Only the predicted survival and death rates calculated by ISS differed significantly from the observed rates. There were also significant differences between ISS and TRISS, and ISS and ASCOT, with regard to the predicted rates. CONCLUSIONS: In our unit ISS, which is simple to use, is not suitable for quality assessment. TRISS and ASCOT are of equal value. We prefer TRISS until a better, internationally recognised score is available, since it involves less effort and is less error-prone. General recommendations for Switzerland cannot be made until further results from other national accident and emergency units are available.

Adolescent↗
PubMed2000

Comb-wax discrimination by honeybees tested with the proboscis extension reflex.

We used the proboscis extension reflex of honeybees to test their ability to discriminate between comb waxes of different ages (wax scales, 1-week-old wax, 2- to 3-year-old wax, 8- to 10-year-old wax). Such waxes differ in their chemical composition, and an ability to discriminate between them may aid the orientation of the bees in the nest. To train the bees, we used whole extracts of waxes and four different fractions of the whole extract based on different elutions of solid-phase extractions (extract I, fraction A eluted with hexane and fraction B with diethylether; extract II, fraction B further subdivided into fraction C by elution with isopropylchloride and fraction D by elution with diethylether). In a differential training regime (six learning and six test trials) with whole extracts or with the different fractions, we paired one type of wax with a reward and another with no reward. The bees learned to discriminate between all tested pairs of whole extracts. The two subfractions (fractions A and B) gave different results: the bees could discriminate between waxes of different ages when fraction B was used but not when fraction A was used. A further subdivision of fraction B into fractions C and D showed that only fraction D contained the elements that enabled bees to discriminate between old and new wax. Fraction D makes up only 5?8 % of the total wax mass and contains hydroxy alkyl esters (5?6 % of the total wax mass), primary alcohols (0.3?0.5 % of the total wax mass) and acids (0.06?1. 0 % of the total wax mass). Fractions A and C (together forming 62?64 % of the total wax mass), which consist of unbranched and branched aliphatic hydrocarbons and alkyl esters, could not be discriminated by the bees. The remaining wax mass (25?29 %) was eluted with a mixture of chloroform, methanol and water (13:5:1) as fraction E.

Animals↗
PubMed1998

Cutin monomers and surface wax constituents elicit H2O2 in conditioned cucumber hypocotyl segments and enhance the activity of other H2O2 elicitors

Hypocotyls from etiolated cucumber (Cucumis sativus L.) seedlings were gently abraded at their epidermal surface and cut segments were conditioned to develop competence for H2O2 elicitation. Alkaline hydrolysates of cutin from cucumber, tomato, and apple elicited H2O2 in such conditioned segments. The most active constituent of cucumber cutin was identified as dodecan-1-ol, a novel cutin monomer capable of forming hydrophobic terminal chains. Additionally, the cutin hydrolysates enhanced the activity of a fungal H2O2 elicitor, similar to cucumber surface wax, which contained newly identified alkan-1,3-diols. The specificity of elicitor and enhancement activity was further elaborated using some pure model compounds. Certain saturated hydroxy fatty acids were potent H2O2 elicitors as well as enhancers. Some unsaturated epoxy and hydroxy fatty acids were also excellent H2O2 elicitors but inhibited the fungal elicitor activity. Short-chain alkanols exhibited good elicitor and enhancer activity, whereas longer-chain alkan-1-ols were barely active. The enhancement effect was also observed for H2O2 elicitation by ergosterol and chitosan. The physiological significance of these observations might be that once the cuticle is degraded by fungal cutinase, the cutin monomers may act as H2O2 elicitors. Corrosion of cutin may also bring surface wax constituents in contact with protoplasts and enhance elicitation.

Journal Article↗
PubMed1997

Dissociation of antithrombotic effect and bleeding time prolongation in rabbits by inhibiting tissue factor function.

Inhibition of the tissue factor/factor VIIa (TF/F.VIIa) complex attenuates thrombosis in different animal models of arterial thrombosis. However, it remains unclear to what extent the antithrombotic effects are associated with changes in hemostatic functions and how this compares with inhibition of thrombin, an enzyme acting at a later stage in the coagulation cascade. The antithrombotic and the antihemostatic effects of a monoclonal anti-TF antibody (AP-1) were compared in a model of arterial thrombosis to those of a direct thrombin inhibitor (napsagatran) and heparin. In anesthetized rabbits transient arterial thrombi were induced by mechanical damage to the subendothelium of a moderately stenosed carotid artery. Recurrent formation and dislodgement of thrombi resulted in cyclic flow variations (CFVs) which were monitored over 2 hours. Rabbits received intravenously either a placebo (control), a monoclonal anti-rabbit TF antibody (AP-1, 0.05 mg/kg as an i.v. bolus repeated every 15 min, a specific low molecular weight thrombin inhibitor (napsagatran, 3 microg/kg/min) or heparin (3 and 13 microg/kg/min). The effect of the inhibitors on the hemostatic system was studied in a separate set of rabbits by measuring template bleeding times (BT) in the ear arterioles, marginal ear vein and the nail cuticle of the foreleg. AP-1 and napsagatran showed a similar antithrombotic activity (78% and 80% abolition of the CFVs, respectively), whereas either low or high dose heparin was poorly effective (43% and 40% inhibition of CFVs, respectively). At these antithrombotic doses and even at 4-fold higher dosage, AP-1 did not significantly alter the BT, whereas napsagatran and heparin prolonged the ear vessels and cuticle BT in a dose-dependent manner. These results suggest that in contrast to direct thrombin inhibition, the blockade of the TF/F. VIIa function did not result in a concomitant prolongation of the bleeding time. Thus, dissociation of antithrombotic and antihemostatic effects indicates that inhibition of the coagulation system at its initial stage represents a promising approach for the development of new anticoagulants.

Animals↗
PubMed1994

[Successful drug therapy of persistent ectopic pregnancy after tube-saving operation].

We report on a 29-year old woman, gravida 1, para 0, who complained, after 6 weeks of amenorrhoea, of vaginal bleeding and acute pain in the lower left abdomen. A non-ruptured left ampullary tubal pregnancy was recognised at diagnostic laparoscopy and removed by tube-preserving surgery. Subsequently, serum human chorionic gonadotropin (hCG) was quantified every two days; a rising hCG concentration confirmed a persistent ectopic gestation in the patient. 12 days after conservative laparoscopic surgery, treatment with methotrexate (1 mg/kg intramuscularly a day) during 4 days was initiated. After another brief rise, the hCG concentration dropped continuously down and was no longer detectable after 2 months.

Adult↗
PubMed1985

Accumulation and transport of (2,4-dichlorophenoxy)acetic acid in plant cuticles. II. Permeability of the cuticular membrane.

Diffusion of (2,4-dichlorophenoxy)acetic acid (2,4-D) across plant cuticles from 10 species was investigated at 25 degrees C using enzymatically isolated cuticles. Permeance coefficients (P) and extrapolated holdup times (te) were measured and permeability (P), diffusion (D), and partition coefficients (K) were calculated. Permeance coefficients ranged from 2.72 X 10(-8) (Capsicum fruit) to 1.00 X 10(-10) m/sec (Ficus leaf). Extraction of soluble cuticular lipids from cuticular membranes increased permeances by up to four orders of magnitude. This demonstrates that permeance is determined by the soluble cuticular lipids associated with the cutin, rather than by cutin alone. Mean diffusion coefficients calculated from holdup times were 4.0 X 10(-15) (fruit cuticular membranes) and 1.71 X 10(-16) m2/sec (leaf cuticular membranes), respectively. Since a common diffusion coefficient exists for both leaf and fruit cuticles, differences in permeability coefficients between species can be attributed to differences in the partition coefficients. However, partition coefficients calculated from transmembrane diffusion are lower than those determined directly in a sorption experiment by a factor of from 6 to 200. Thus, the high resistance of plant cuticles to transport of 2,4-D can be attributed to both low diffusion and partition coefficients in the transport-limiting layer made up of cutin and soluble lipids which are densely packed and highly ordered. A linear equation is derived and permits the prediction of permeability coefficients of plant cuticles from partition coefficients determined in a simple sorption experiment.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1984

Accumulation and transport of (2,4-dichlorophenoxy)acetic acid in plant cuticles: I. Sorption in the cuticular membrane and its components.

Partition coefficients (K) of (2,4-dichlorophenoxy)acetic acid (2,4-D) have been determined for the system plant cuticle/aqueous buffer. Cuticles isolated enzymatically from leaves (Clivia miniata, Ficus elastica, Citrus aurantium, Hedera helix, Pyrus communis cv. Conférence and cv. Williams, Olea europaea) and fruits (Lycopersicon esculentum, Capsicum annuum, Solanum melongena, Cucumis sativus) were utilized. Only the nondissociated species of 2,4-D was sorbed by cuticles and their lipophilic components. The average partition coefficient for leaf cuticles was 316 (range, 240-470) and for fruit cuticles 476 (range, 424-579). The dependence of sorption upon 2,4-D concentration was tested using tomato fruit cuticle. The sorption isotherm was linear from 2.0 to 5.0 X 10(-4) mol m-3. With increasing 2,4-D concentrations partition coefficients decreased slightly. Extraction of soluble cuticular lipids (SCL) increased the partition coefficients and these relative increases were correlated to relative amounts of SCL. In most species the hydrolytic removal of polar cuticular components resulted in a further increase of partition coefficients. No single cuticle was found to be representative for the sorption characteristics of all plant species investigated. The amounts of cuticle present in plant communities can be estimated from the data presented in conjunction with leaf area indices.

2,4-Dichlorophenoxyacetic Acid↗
PubMedDate not supplied

[Psychopathology of senile dementias in nursing home residents].

Examination of 163 nursing home residents revealed chronic brain syndrome of different amount in 84%. Demented patients with clinical evidence of arteriosclerosis had significantly higher values of emotional incontinence, dysphoria, depression and vegetative complaints than those without evidence of arteriosclerosis. Correlation of single psychopathologic parameters with other psychopathologic, neurologic and somatic variables resulted in very different correlation profiles for the following symptoms: emotional incontinence, apathy, dysphoria and euphoria. These changes in personality should be considered to a higher degree in dementia research intending more homogeneous subgroups.

Aged↗