Search PubMed⌕ Search

Biomedical subjects

B Wilhelm

Publications and source records attributed to B Wilhelm.

At least 55 records · Page 3Linked to original sources
PubMed1993

Activation of the cloned platelet thrombin receptor decreases the pertussis-toxin-dependent ADP-ribosylation of the membrane and soluble inhibitory guanine-nucleotide-binding-alpha proteins. Inhibition by the prostacyclin analog, iloprost.

Thrombin binds at least to two sites of the platelet surface; to the recently cloned thrombin receptor [Vu, T. K., Hung, D. T., Wheaton, V. I. & Coughlin, S. R. (1991) Cell 64, 1057-1068] and to glycoprotein Ib. In the present study, the decrease of pertussis-toxin-dependent ADP-ribosylation of membrane and soluble inhibitory guanine-nucleotide-binding alpha (Gi alpha) proteins was measured after platelet stimulation with a thrombin-receptor-activating peptide (TRAP), and compared to stimulation with thrombin. Stimulation of intact platelets with TRAP decreased the pertussis-toxin-dependent ADP-ribosylation of the major membrane 41-kDa Gi alpha protein and the minor soluble 40 kDa Gi alpha protein recently described in platelets [Gennity, J. M. & Siess, W. (1991) Biochem. J. 279, 643-650]. The kinetics and extent of the decrease of pertussis-toxin-dependent ADP-ribosylation after stimulation of TRAP were similar to the effect of thrombin. The decrease of pertussis-toxin-dependent ADP-ribosylation of the soluble Gi alpha protein was more pronounced and observed at lower agonist concentrations than the decrease of the membrane Gi alpha protein. Desensitization of the thrombin receptor by incubating platelets with a low concentration of TRAP reduced the subsequent decrease of pertussis-toxin-dependent ADP-ribosylation of Gi alpha proteins, evoked by TRAP or thrombin. Platelet stimulation with gamma-thrombin that does not bind to glycoprotein Ib also showed a decrease in the pertussis-toxin-dependent ADP-ribosylation of the soluble and membrane Gi alpha proteins. Treatment of platelets with the stable prostacyclin analog, iloprost, reduced the decrease of pertussis-toxin-dependent ADP-ribosylation of Gi alpha proteins induced by TRAP or thrombin. Among other platelet stimuli tested (endoperoxide/thromboxane analog U44619, collagen, ADP, vasopressin), only U44619 decreased the pertussis-toxin-dependent ADP-ribosylation of the soluble and membrane Gi alpha proteins to a degree comparable to TRAP. It is concluded that the thrombin-induced activation of both the membrane and soluble Gi alpha proteins in platelets occurs via stimulation of the recently cloned thrombin receptor and is independent of the binding of thrombin to glycoprotein Ib. Furthermore, the coupling thrombin receptor/Gi protein is reduced by intracellular cAMP.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

[Age dependence of pupillary near reflex].

BACKGROUND: This study was performed to gain age correlated normal values for the pupillary near reflex. METHODS: Accommodation and pupillary near reaction were measured by means of simultaneous infrared video retinoscopy and pupillography in 64 healthy volunteers aged between 5 and 55 years. Measurements were done at a reduced, near mesopic, light condition with accommodation to 10, 14, 20 and 33 cm. RESULTS: The pupillary near response varied highly with age: persons younger than 20 years of age showed a significantly smaller pupillary near response as compared to those older than 20 years. In most of the children younger than 10 years the pupil near response was very small (less than 10% constriction) at accommodation distances longer than 10 cm. There was a significant difference between the age groups younger and older than 20 but no statistically significant differences within these age groups. CONCLUSION: A change of the pupillary near reaction takes place around the age of 20. We conclude that this change does not only reflect the aging of the cristalline lens but is due to an age related change of the supranuclear control.

Accommodation, Ocular↗
PubMed1993

Human alpha 1-antichymotrypsin of pancreatic origin carries blood group determinants.

alpha 1-Antichymotrypsin was detected as a minor but normal component of pancreatic juice and found, with the aid of monoclonal antibodies and lectins, to differ from serum alpha 1-antichymotrypsin with respect to its carbohydrate moiety. alpha 1-Antichymotrypsin carries blood group determinants, as is typical for glycoproteins of pancreatic origin.

Antibodies, Monoclonal↗
PubMed1992

Diversity of B2 bradykinin receptors with nanomolar affinity expressed in passaged IMR90 human lung fibroblasts.

IMR90 human fetal lung fibroblasts express bradykinin receptors activating the pathway for biosynthesis of PGE2. A receptor of the B2 subtype stimulates half-maximal PGE2 production at 4.8 nM bradykinin, and maximal output takes place at 25 nM bradykinin. Radioligand binding studies reveal a population of [3H]bradykinin binding sites whose affinity correlates with this B2 receptor's biologic activity, with a KD of 2.5 nM. As IMR90 cells reach 60% of their defined life span in culture, they spontaneously induce expression of a second site of lower affinity, with half-maximal binding of [3H]bradykinin at 44 nM. This second site displays a characteristic primary B2 receptor recognition profile, but differs from the 2.5 nM site on a secondary level in recognition among different B2 ligands. Bradykinin is the most potent ligand at both sites; they each preferentially recognize an N-terminal extended bradykinin peptide construct having selectivity for the rat myometrial B2 receptor, suggesting that both sites have structural features in common. However, they display diversity in their order of preference for Met-Lys-bradykinin versus Lys-Lys-bradykinin; at the 44 nM site this order is completely reversed from the order of potency exhibited at the 2.5 nM site. Expression of the second site changes the manner in which these fibroblasts control their PGE2 production; it affords a graded response of PGE2 production at bradykinin levels beyond those which would normally saturate the 2.5 nM site. The inducibility of the 44 nM site in cultured fibroblasts addresses in vivo conditions in an inflammatory environment where continuing generation of bradykinin-related peptides takes place and presents a possible mechanism for overriding constraints that would otherwise limit the progression of inflammation.

Amino Acid Sequence↗
PubMed1992

Platelet signal transduction mechanisms induced by eicosanoids.

Platelets are in many ways involved in the pathogenesis of artherosclerosis and the development of coronary heart disease, and play a role in acute myocardial infarction (8). They are also an useful model to study cellular activation mechanisms: their isolation from peripheral venous blood is simple and rapid and their physiological responses such as shape change, aggregation and secretion can be easily measured (10). This chapter is focused on our results on the mechanisms of platelet activation and inhibition induced by eicosanoids.

Blood Platelets↗
PubMed1991

Ca2+ ionophore A23187 and thrombin inhibit the pertussis-toxin-induced ADP-ribosylation of the alpha-subunit of the inhibitory guanine-nucleotide-binding protein and other proteins in human platelets.

Inhibitory guanine-nucleotide-binding proteins (Gi proteins) are substrates for pertussis toxin and the decreased pertussis-toxin-dependent ADP ribosylation of Gi proteins upon prior specific hormonal stimulation of cells is thought to reflect the receptor-mediated activation of Gi proteins, leading to their subsequent dissociation into alpha i and beta/gamma subunits. In the present study, the effect of various platelet stimuli on the subsequent pertussis-toxin-dependent ADP ribosylation of the alpha subunit of Gi (Gi alpha) in saponized platelets and platelet membranes were studied. Stimulation of intact platelets with the Ca(2+)-ionophore A23187 or thrombin, but not phorbol 12,13-dibutyrate, decreased the subsequent pertussis-toxin-dependent ADP ribosylation of Gi alpha in saponin-permeabilized platelets in a time-dependent and dose-dependent manner. Thrombin was more effective than A23187. Parallel measurements of Ca2+ mobilization and pertussis-toxin-dependent ADP ribosylation of Gi alpha in platelets showed that Ca2+ mobilization could only partly account for the decrease in pertussis-toxin-dependent ADP ribosylation in platelets stimulated by thrombin. When the ADP-ribosylation reaction was carried out in platelet membranes, a decrease in ADP ribosylation was still observed after stimulation of platelets with thrombin, but not with A23187. In addition to Gi alpha, two other proteins were found to be ADP ribosylated by pertussis toxin; their ADP ribosylation was also decreased after A23187 and thrombin stimulation of platelets. The results indicate that Ca2+ mobilization can decrease the pertussis-toxin-dependent ADP ribosylation of Gi alpha in saponized platelets; the decrease of pertussis-toxin-dependent ADP ribosylation of Gi alpha after thrombin stimulation of platelets can only, in part, be explained by Ca2+ mobilization and involves additional mechanisms; the decrease in pertussis-toxin-dependent ADP ribosylation after A23187 and thrombin stimulation is not confined to G1 alpha and involves other proteins. We conclude that the decrease in pertussis-toxin-dependent ADP ribosylation of Gi in thrombin-stimulated platelets might not be solely caused by a specific structural change, such as dissociation of Gi. It is likely that A23187 and thrombin stimulation of platelets generates substances which interfere with the ADP-ribosylating activity of pertussis toxin.

Adenosine Diphosphate Ribose↗
PubMed1991

[Sacral bedsore: an evaluation of 10 years' treatment with the gluteus maximus muscle].

The authors review the notes of 40 patients who underwent surgery for large sacral pressure sore over the last 10 years. In most cases a gluteus maximus flap with skin graft has been employed to cover sacral sore, as originally described by Ger in 1971. The results of this series are then compared with those published by other authors using different techniques, with particular attention to gluteus maximus musculo-cutaneous island flaps and purely cutaneous flaps. All procedures carry a small mortality rate because of the advanced age and frail conditions of most patients. In our series 2 patients died in the postoperative period; in all the others we eventually achieved a sound healing of the sacral sore. We conclude that the gluteus maximus rotation flap is a safe and effective for the treatment of this condition. Its only major drawback is represented by the prolonged period required for the epithelisation by secondary intention of some fairly frequent areas of failure on the skin graft. The importance of a multidisciplinary team approach in the management of these patients cannot be overemphasised.

Aged↗
PubMed1991

[Mydriasis caused by plant contact].

Uni- or bilateral dilatation of pupils that are not reactive to light and lack miosis in response to 1% pilocarpine may be caused by contact with plants containing alkaloids such as scopolamine and atropine. Other causes of a non-light-reactive dilated pupil, such as Adie's tonic pupil, third nerve palsy and lesion of the mesencephalic pretectal region, must be excluded before testing the iris sphincter reaction to 1% pilocarpine. Among the naturally growing flowers in Germany, deadly nightshade (Atropa belladonna), jimson weed (thornapple, Datura stramonium) and black henbane (Hyoscyamus niger) contain enough alkaloids to cause mydriasis by direct contact. However, in most cases an accidental mydriasis by plants in Germany is caused by Datura arborea taxa, e.g. Datura suaveolens, D. candida, D. aurea and D. sanguinea. They contain up to 0.6% dry weight scopolamine. These plants can grow very large and are often planted in tubs. They have to be cut back each year before the winter. This is typically how the eye is contaminated by parts of the plants, which can cause dilatation of the pupil mimicing a neuroophthalmological disorder.

Diagnosis, Differential↗
PubMed1990

Distinct binding sites of Ala48-hirudin1-47 and Ala48-hirudin48-65 on alpha-thrombin.

The interaction of alpha-thrombin with Ala48-hirudin, Ala48-hirudin1-47, and Ala48-hirudin48-65 was analyzed. Mutations at Pro48 were found to cause only slight changes in the kon (human: 3.1 +/- 0.3 x 10(8) M-1 s-1; bovine: 1.03 +/- 0.3 x 10(8) M-1 s-1) and koff (human: 0.4 +/- 0.2 x 10(-3) s-1; bovine: 2.9 +/- 0.4 x 10(-3) s-1) rate constants for the formation of the thrombin-hirudin complex. The amino-terminal fragment Ala48-hirudin1-47 containing the three disulfide bridges and the carboxyl-terminal fragment Ala48-hirudin48-65 were derived from the Ala48 mutant by proteolysis with endoproteinase Lys-C. These fragments inhibit bovine alpha-thrombin clotting activity with IC50 values of 0.6 and 4.9 microM, respectively (2.4 nM for r-hirudin). By mapping the interaction of Ala48-hirudin-derived fragments with bovine alpha-thrombin by limited proteolysis with trypsin and pancreatic elastase distinct binding sites for each fragment were determined. The carboxyl-terminal fragment was found to bind to the proposed anion-binding exosite in the region B62-74, whereas the amino-terminal fragment binds to a region around the elastase cleavage site at residues 150-151 of the alpha-thrombin B-chain.

Alanine↗
PubMed1978

Effect of tetramethylammonium ions on conformational changes of DNA in the premelting temperature range.

The reversible conformational change of DNAs and polydeoxyribonucleotides occurring before melting was followed by circular dichroism. deltatheta/deltaT, the rate of change of ellipticity theta with temperature, was used mainly as a measure of this premelting phenomenon. If sodium ions were replaced by tetramethylammonium ions deltatheta/deltaT decreased for poly (dA) poly (dT) and poly (dA.dT) poly (dT.dA), but increased for poly (dG.dC) poly (dC.dG). DNAs of different base composition showed no more premelting (deltatheta/deltaT approximately 0) even at low molarities of TMACl provided the Na/TMA ratio was very small. For all cases studied the theta values at 0 degrees C and at a given ionic strength were smaller in NaCl than in TMACl. When studying the series of ammonium ions from NH4+ to (C2H5)4N+, the deltatheta/deltaT values first decreased, going through zero with TMA+ ions, and then increased again. A tentative and qualitative explanation of our results can be given: (a) Hydration of the polymers increases in presence of TMA ions and their average stability decreases; locally, however, (AT) pairs are preferentially stabilized by TMA ions owing to a specific interaction at the level of O2 of thymine. (b) In order to explain the different behaviour of (AT) polymers and DNA, it is assumed that only the B structure is able to accommodate TMA ions in the small groove of the double stranded helix.

Chemical Phenomena↗
PubMed1977

[Pancreatic injuries].

Within a constant increase in the number of injured in the last ten years a significant rise in the number of abdominal injuries has been noticeable. From 1,2% of ten years ago, abdomeninal injuries have risen to 4,6% of the total number of treated patients. While in earlier years pancreatic injuries were a rarity, in 1974 there were six patients with an injury to the pancreas due to either a blunt or penetranting wound of the abdomen. Out of altogether (21) treated patients only in one was an isolated injury to the pancreas found. We have never been able to recognise with certainty the injury to the pancreas with clinical methods, but only surgical exploration enabled us to make an accurate diagnosis. In all surgically treated pancreatic injuries a suture of the capsule of the pancreas was done after débridement and minute hemostasis. Only in one case of complete transversal rupture of the corpus we decided upon a resection and a blind closure of the truncus. The site of the injury was obligatorily repeatedly drained in order to remove pancreatic secretions from the abdominal cavity. Out of the total number of patients surgically operated were 12, of whom 7 died. Other patients could not be operated upon because of the traumatic shock, so that pancreatic traumas in these patients were discovered at a postmortem examination.

Abdominal Injuries↗