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R Beckmann

Publications and source records attributed to R Beckmann.

At least 55 records · Page 3Linked to original sources
PubMed1992

Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by electric field stimulation.

We investigated the relaxant effect of electric field stimulation (EFS) on rabbit cavernous smooth muscle strips in vitro precontracted by phenylephrine. Effects of EFS were monitored alone, and following muscarinic receptor blockade, and inhibition of nitric oxide (NO) formation by L-N-monomethylarginine (L-NMMA) or by L-N-nitroarginine (L-NOARG). Atropine only slightly reduced the relaxant effect of EFS to 89.0 +/- 6.1 percent. Additional application of L-NMMA further reduced the relaxant effect to 37.3 +/- 15.3 percent. Substitution of L-NOARG for L-NMMA led to a more pronounced inhibition of relaxant effects to 16.2 +/- 8.7 percent. The results indicate that neurogenically induced relaxation of rabbit cavernous smooth muscle is mediated mainly by NO formation and argue against a substantial role of relaxing peptidergic neurotransmitters, such as vasoactive intestinal polypeptide and calcitonin-gene-related peptide, in penile erection.

Animals↗
PubMed1992

GTP-binding proteins in bovine brain nuclear membranes.

Nuclear membranes and other subcellular fractions derived from bovine brain cortex were investigated for the existence of GTP-binding proteins. By using photolytic labeling with [alpha-32P]GTP a 29 kDa GTP-binding protein was shown to be present in nuclear membranes which was not present in the plasma membranes nor in microsomal or cytosolic fractions. Two-dimensional gel electrophoresis revealed that this protein is rather acidic with a pI lower than 4.5. Members of the heterotrimeric Gi/o family are not present in the nuclear envelope: a 39 kDa protein, ADP ribosylated by pertussis toxin, was shown to originate from plasma membrane contamination.

Adenosine Diphosphate Ribose↗
PubMed1991

Fibronectin decreases the stimulatory effect of fibrin and fibrinogen fragment FCB-2 on plasmin formation by tissue plasminogen activator.

Fibronectin is a dimeric glycoprotein (Mr 440,000) involved in many adhesive processes. During blood coagulation it is bound and cross-linked to fibrin. Fibrin binding is achieved by structures (type I repeats) which are homologous to the "finger" domain of tissue plasminogen activator. Tissue plasminogen activator also binds to fibrin via the finger domain and additionally via the "kringle 2" domain. Fibrin binding of tissue plasminogen activator results in stimulation of its activity and plays a crucial role in fibrinolysis. Since fibronectin might interfere with this binding, we studied the effect of fibronectin on plasmin formation by tissue plasminogen activator. In the absence of fibrin, fibronectin had no effect on plasminogen activation. In the presence of stimulating fibrinogen fragment FCB-2, fibronectin increased the duration of the initial lag phase (= time period until maximally stimulated plasmin formation occurs) and decreased the rate of maximal plasmin formation which occurs after that lag phase mainly by increasing the Michaelis constant (Km). These effects of fibronectin were dose-dependent and were similar with single- and two-chain tissue plasminogen activator. They were also observed with plasmin-pretreated FCB-2. An apparent Ki of 43 micrograms/ml was calculated for the inhibitory effect of fibronectin when plasminogen activation by recombinant single-chain tissue plasminogen activator was studied in the presence of 91 micrograms/ml FCB-2. When a recombinant tissue plasminogen activator mutant lacking the finger domain was used in a system containing FCB-2, no effect of fibronectin was seen, indicating that the inhibitory effect of fibronectin might in fact be due to competition of fibronectin and tissue plasminogen activator for binding to fibrin(ogen) via the finger domain.

Fibrin↗
PubMed1991

Basal and acetylcholine-stimulated nitric oxide formation mediates relaxation of rabbit cavernous smooth muscle.

Externally applied acetylcholine (ACh) in human corpus cavernosum has been shown to cause endothelium-dependent smooth muscle relaxation. Changes in isometric tension in rabbit cavernous smooth muscle strips mounted in organ bath chambers were monitored in the presence of blocking agents. Nitric oxide (NO) is known as an endothelium-derived relaxation factor (EDRF). Addition of specific inhibitors of nitric oxide synthesis, such as L-n-monomethyl arginine (L-NMMA) at 5 x 10(-4) mol/l.. or L-n-nitro arginine (L-NOARG) at 2 x 10(-4) mol/l. to strips precontracted with phenylephrine (PE) at 3.16 x 10(-6) mol/l. led to significant increases in tension. In the presence of L-NMMA or L-NOARG, relaxing effects of ACh at 10(-8)-3.16 x 10(-5) mol/l. mediated by muscarinic receptors were almost completely abolished. These data indicate that rabbit cavernous smooth muscle is under the control of basal NO release. They constitute strong evidence that cholinergically induced endothelial formation of NO plays a crucial role in relaxing cavernous smooth muscle.

Acetylcholine↗
PubMed1990

Steroid receptors and proliferative activity in non-neoplastic and neoplastic endometria.

In the glands of cyclic endometria, proliferative activity (PA), as revealed by expression of the Ki-67 antigen, is highest in the proliferative phase (P) and early secretory phase (S1). The PA decreases in the middle secretory phase (S2). In the stroma the PA is low during the whole cycle. In P and S1, the oestrogen receptor (ER) and the progesterone receptor (PR) are strongly expressed in glands and stroma. The number of positive cells and the staining intensity decreases in S2, particularly in the glands. In atrophic endometria, fibro-glandular polyps and in endometria with arrested secretion the PA is low in both glands and stroma. ER and PR can be detected in glands and stroma. The PA in atypical hyperplasias is only slightly higher than in cyclic endometria and endometria with simple hyperplasia. The ER and PR levels are comparable to those in proliferative endometria. The PA of endometrial adenocarcinomas is positively and the ER and PR negatively correlated with the degree of de-differentiation. No ER-negative carcinoma displays the PR. Immunohistologically, non-neoplastic receptor positive tissue can be seen in many ER- and PR-negative carcinomas. These structures may falsify the biochemical receptor analysis.

Adult↗
PubMed1989

Functional characterization of monoclonal antibodies directed against fibrin binding domains of tissue-type plasminogen activator.

Fibrin interacts with tissue-type plasminogen activator (tPA) via the finger and the kringle 2 domains. Three monoclonal antibodies against tPA, designated MPW3VPA, MPW6VPA, and MPW7VPA, which react with epitopes in the tPA molecule involved in fibrin binding, were characterized. The IgM monoclonal antibody MPW6VPA, directed against an epitope close to the finger and epidermal growth factor domains, stimulated plasminogen activation only in the absence of CNBr-fibrinogen fragments by increasing kcat in a dose-dependent fashion, an effect which was not restricted to the intact molecule. These results suggest that MPW6VPA mimics the initial effect of fibrin bound to the tPA molecule, which results in a change of kcat values. The MPW6VPA effect was reversed by another antibody, MPW3VPA, also directed against epidermal growth factor and finger domains. The latter antibody also inhibited plasminogen activation by tPA in the presence of CNBr-fibrinogen fragments in a dose-dependent, apparently noncompetitive way. No effect of MPW3VPA was seen in the absence of CNBr-fibrinogen fragments. MPW7VPA directed against kringle 2 of tPA inhibited plasminogen activation by tPA only when CNBr-fibrinogen fragments were present. This inhibition was apparently competitive and dose-dependent. These data suggest that MPW3VPA interferes with the first phase of fibrin binding to tPA, whereas MPW7VPA interferes with the second phase of fibrin binding to the tPA molecule via kringle 2, resulting in Km changes.

Antibodies, Monoclonal↗
PubMed1989

Enzyme linked immunosorbent assays (ELISA) for the quantitative determination of human leukocyte collagenase and gelatinase.

A competitive and a sandwich enzyme linked immunosorbent assay (ELISA) were developed for human leukocyte collagenase and gelatinase. The competitive assay could detect 0.5 ng collagenase and 0.05 ng gelatinase. The detection limit of the sandwich ELISA was 0.05 ng for collagenase and 0.02 ng for gelatinase. No cross reactivity between human leukocyte collagenase and gelatinase was detected. The sandwich ELISA was used to determine plasma levels of these enzymes. The 90% range for collagenase was between 0 and 50 micrograms/l; the 90% range for gelatinase was between 27 and 94 micrograms/l.

Blotting, Western↗
PubMed1989

Hereditary progressive muscular dystrophies: serum myoglobin pattern in patients with different types of muscular dystrophies.

Serum myoglobin (Mb) levels and creatine kinase (CK) activity were investigated in patients with different types of progressive muscular dystrophy and controls. The Mb levels were determined by radioimmunoassay and found to be significantly elevated in all patients under resting conditions. There was no correlation between Mb levels and CK activity. Physical exercise was followed by an increase in Mb levels and CK activity in patients and a minor variation in controls. Isoelectric focusing, electroblotting and application of a specific Mb antibody (rabbit anti-human Mb) make it possible to recognize marked differences between the Mb bands of patients and controls. All patients with progressive muscular dystrophy had an additional fourth Mb band (isoelectric point pH 6.3) in contrast to controls with three Mb bands.

Creatine Kinase↗
PubMed1988

A double-blind placebo controlled trial of diltiazem in Duchenne dystrophy.

The role of calcium accumulation in the pathogenesis of Duchenne muscular dystrophy (DMD) has already been discussed. Several trials with different calcium-blocking drugs have revealed no clinical benefit. In addition, the present study includes histological investigations and computer tomography to verify therapeutic effects. In a randomized placebo-controlled double-blind study, 13 DMD patients aged from 3-10 years (mean, 7 years) were treated with 5 mg/kg diltiazem daily for 1 year. Compared with before therapy, the number of calcium-positive muscular fibres was remarkably reduced in the treated DMD patients, but not in the placebo group. The evaluation of all other biochemical and clinical parameters revealed no significant effects of the diltiazem therapy. The muscular X-ray density measured by computer tomography decreased under treatment. After the evaluation of the double-blind study, the code was broken. Therapy, however, was continued in the treated group and started in the placebo group. After 3 years of diltiazem therapy the clinical status of all 26 patients of the study and 20 additional DMD patients who were treated with diltiazem was compared with 46 untreated DMD patients of the same age and stage in our department. No obvious clinical benefit of diltiazem therapy could be observed.

Calcium↗
PubMed1988

Plasminogen activation by tissue plasminogen activator in the presence of stimulating CNBr fragment FCB-2 of fibrinogen is a two-phase reaction. Kinetic analysis of the initial phase of slow plasmin formation.

Plasminogen activation by tissue-type plasminogen activator (t-PA) is stimulated by fibrin. In a purified system maximal fibrin-enhanced plasmin formation occurs with a delay after an initial phase of slow plasmin formation (lag phase). In the present study purified stimulating CNBr-fragment FCB-2 of fibrinogen was used, and kinetics of plasminogen activation by t-PA were analyzed with respect to the lag phase. At constant FCB-2 concentration the duration of the lag phase decreased with increasing concentrations of t-PA and plasminogen. During this period the rate of plasmin formation/min increased linearly with time with a slope dependent on the initial concentrations of FCB-2, plasminogen, and t-PA. Plasmin pretreatment of FCB-2 resulted in a dose- and time-dependent shortening of the lag phase, and at plasmin concentrations greater than or equal to 1 nM and preincubation times greater than or equal to 3 min maximal plasmin formation occurred without a lag phase. Kinetics during the phase of maximal and constant plasmin formation were not influenced by plasmin pretreatment of FCB-2. We therefore conclude that maximal t-PA-dependent plasmin formation in a system stimulated by purified FCB-2 requires plasmin modification of FCB-2.

Cyanogen Bromide↗
PubMed1988

Pharmacological profile of a new potent 5-hydroxytryptamine (5-HT2) alpha 1-receptor antagonist.

In in vitro binding studies ZK 33.839 (4-(3-[3-(4-(4-fluorobenzoyl)-1-piperidinyl)-propoxy]-4-methoxyphenyl)- 2-pyrrolidone) showed highly specific binding affinity for 5-hydroxytryptamine (5-HT2) and alpha 1-receptors. With 2.0 nmol/l and 5.2 nmol/l both Ki-values occur in the same concentration range. The pharmacodynamic profile of ZK 33.839 has been investigated under in vitro and in vivo conditions. In human platelets, in rat vascular smooth muscle and in guinea pig tracheal smooth muscle 5-HT-induced proaggregatory and contractile effects were inhibited dose-dependently with IC50-values ranging from 1.85 x 10(-8) mol/l to 9 x 10(-9) mol/l. 5-HT-induced amplification of the response of rabbit femoral artery to different vasoconstrictors (angiotensin II, histamine, norepinephrine, and prostaglandin F2 alpha) and 5-HT-mediated increase of microvascular permeability in hamster cheek pouch preparation were also inhibited by ZK 33.839. ZK 33.839 was found to be a potent alpha 1-receptor antagonist, the pA2-value in rat aortic strips determined against phenylephrine was 9.16. In blood-perfused hindquarters of anaesthetized rats, pretreated with reserpine, pressor dose-response curves to norepinephrine and 5-HT were shifted to a higher dose range. ZK 33.839 lowered blood pressure in conscious Dahl-S-rats and in anaesthetized rabbits. Decrease of blood pressure was due to a decrease of peripheral vascular resistance. Cardiac output and heart rate were not significantly altered. ZK 33.839 is a potential antihypertensive compound which combines vasodilatatory effects due to selective alpha 1-receptor antagonistic action and platelet antiaggregatory, antivasospastic, and vasoprotective properties due to selective 5-HT2-receptor blockade.

Adrenergic alpha-Agonists↗
PubMed1986

A mathematical analysis of creatine kinase activity in the course of Duchenne muscular dystrophy.

Recently, clinical follow-up studies have shown that the age of first symptoms and the speed of progress may vary considerably in Duchenne muscular dystrophy (DMD). Prognostic factors would be of interest not only for the patients themselves, but also for the selection of DMD patients for therapeutic studies. Creatine kinase (CK) activity reflects the dystrophic degeneration of the muscle cells. Therefore, the coherence of the course of CK activity and its relationship to the clinical state was investigated with the aid of a heuristic mathematical formula. Two constants were calculated, b and c. The data of 88 DMD patients proved the validity of the mathematical formula. Constant b seemed to be of no clinical relevance. The height of constant c was related to the age at which the ability to walk was lost (r = -0.76). This constant provides an objective individual assessment of the prognosis in DMD. In addition, the mathematical analysis of the CK course opens the way for a prospective CK estimation, which is relevant for the evaluation of therapeutic trials.

Adolescent↗
PubMed1986

Pharmacological studies on the intrinsic sympathomimetic activity of the beta-adrenoceptor antagonist mepindolol.

1-Isopropylamino-3-(2-methyl-4-indolyloxy)-2-propanol (mepindolol, Corindolan) is a beta-adrenoceptor antagonist with significant intrinsic sympathomimetic activity (ISA): positive chronotropic effects in atria of the rat amount to 24% of those elicited by the full agonist isoprenaline. Relaxant effects in blood vessels approach 50% of those of isoprenaline. This vasorelaxant effect is completely blocked by the specific beta 2-adrenoceptor antagonist ICI 118 551 (erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobut an-2-ol), suggesting that the vasodilatory effects of mepindolol are elicited by stimulation of vascular beta 2-adrenoceptors. In the anaesthetized cat mepindolol acutely lowers arterial blood pressure by reducing total peripheral resistance without exhibiting significant cardiodepressant action, whereas propranolol, lacking ISA, lowers blood pressure by a marked reduction of cardiac output and left ventricular contractility, however, total peripheral resistance is significantly increased.

Adrenergic beta-Antagonists↗
PubMed1984

[Recent clinical knowledge of cytoplasmic substances in myogenic and neuromuscular diseases, especially in muscular dystrophy, Duchenne type].

Up to now there has been no known causal therapy of numerous myogenic and neuromuscular diseases. Among other disorders the genetic muscular dystrophies--especially the malignant Duchenne type, as well as the spinal and neuromuscular dystrophies--cause considerable problems in therapy. Nevertheless there are possibilities of positively influencing the clinical picture and course of the disease by skillful physical training and symptomatic medication. It is sometimes possible, by means of such therapy, to obtain--within limitations imposed by irreparable lesions-stabilization of the clinical state with prolongation of walking ability and amelioration of other motor functions. Nevertheless, such improvement is only transient, because in all patients the process progresses sooner or later. Significant effects were registered of so-called cytoplasmic substances or "biological response modifiers" (particles of protoplasm consisting of nuclei, mitochondria, microsomes and membranes of fresh organic material from healthy young animals and animal fetuses) in an uncommonly large collective of boys with Duchenne muscular dystrophy, as evaluated by follow-up control of the serum enzyme index and creatinine creatine excretion rate. The role of calcium and the possible effect of proteinase-inhibitors are discussed among other pathogenetic aspects. Reference is also made to potential therapeutic effects of cytoplasmic substances in spinal and neuromuscular atrophies on the basis of initial preliminary clinical experience in this field.

Cytoplasm↗