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Biomedical subjects

G Müller

Publications and source records attributed to G Müller.

At least 1,063 records · Page 59Linked to original sources
PubMedDate not supplied

Peptide/benzodiazepine hybrids as ligands of CCK(A) and CCK(B) receptors.

The (neuro)hormones gastrin and cholecystokinin (CCK) share a common C-terminal tetrapeptide amide sequence that has been recognized as the message portion while the N-terminal extensions are responsible for the CCK(A) and CCK(B) receptor subtype selectivity and avidity. 1,4-Benzodiazepine derivatives are potent and selective antagonists of these receptors, and according to comparative molecular field analysis, the structures of these nonpeptidic compounds could well mimic the message sequence of the peptide agonists at least in terms of spatial array of the aromatic residues. Docking of a larger series of low molecular weight nonpeptide antagonists to a homology modeling derived CCK(B) receptor structure revealed a consensus binding mode that is further validated by data from site-directed mutagenesis studies of the receptors. Whether this putative binding pocket of the nonpeptide antagonists is identical to that of the message portion of the peptide agonists, or whether it is distinct and spatially separated, or overlapping, but with distinct interaction sites, is still object of debate. Using a 1,4-benzodiazepine core amino-functionalized at the C3 position, related tryptophanyl derivatives were synthesized as mimics of the tetrapeptide and subsequently extended N-terminally with gastrin and CCK address sequences. All hybrid constructs were recognized as antagonists by the CCK(A) and CCK(B) receptors, but their address portions were incapable of enhancing in significant manner selectivity and avidity. Consequently, the binding of the peptide/benzodiazepine hybrids has to be dictated mainly by the benzodiazepine moiety, which apparently prevents optimal interactions of the address peptides with extracellular receptor subdomains. These findings would strongly support the view of distinct binding sites for the message portion of the peptide agonists and the benzodiazepine-based nonpeptide antagonists.

Benzodiazepines↗
PubMedDate not supplied

Cardiac dysrhythmias in children with idiopathic dilated or hypertrophic cardiomyopathy.

To assess the incidence and prognostic significance of cardiac dysrhythmias in children with idiopathic dilated or hypertrophic cardiomyopathy, the clinical course of 59 patients was retrospectively reviewed over a period of 27 years. Dilated cardiomyopathy (DCM) was diagnosed in 28 patients and hypertrophic cardiomyopathy (HCM) in 31 patients. The mean age at the time of diagnosis was 2.8 +/- 0.7 years in DCM patients and 6.7 +/- 0.8 years in HCM patients. Mean follow-up time after diagnosis of cardiomyopathy was 4.1 +/- 1.0 years in DCM patients and 6.6 +/- 0.8 years in HCM patients. Clinically significant cardiac dysrhythmias were found in 17 of 59 patients (29%): 7 of 28 patients (25%) with DCM and 10 of 31 patients (32%) with HCM. The initial diagnosis of a cardiac dysrhythmia was made by standard electrocardiography in 12 of 17 patients (71%) and by 24-hour Holter monitoring in 5 of 17 patients (29%). Ventricular dysrhythmias were present in 5 of 7 patients with dilated cardiomyopathy and in 5 of 10 patients with hypertrophic cardiomyopathy. During the followup time, death occurred in 18 of 59 patients (31%): 8 of 59 patients (14%) died from congestive heart failure and 10 of 59 patients (17%) died suddenly. Among the sudden deaths were 4 of 28 patients (14%) with dilated cardiomyopathy and 6 of 31 patients (19%) with hypertrophic cardiomyopathy. Cardiac dysrhythmias had been documented in 6 of the 10 patients dying suddenly (3 of 4 patients with DCM and 3 of 6 patients with HCM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

[Quantitative morphology of coronary arteriosclerosis and coronary insufficiency in heart hypertrophy (author's transl)].

After post-mortem coronary angiography the degree of ventricular hypertrophy was estimated on 18 hearts. The cases were divided in three groups: 9 hearts with right ventricular hypertrophy, 4 hearts with left ventricular hypertrophy and 5 hearts with hypertrophy of both ventricles. Cytophotometric studies revealed a close correlation between absolute weight of heart segments and DNA content of muscle cell nuclei of both ventricles . Radius and area of lumen, thickness and area of both intima and media were measured at serial cross sections of all three coronary arteries. Using these data indices on coronary sclerosis and, including the heart weight, indices on coronary insufficiency were calculated. By determining these indices for the isolated right and left ventricle and the interventricular septum additional criteria suggesting failure of coronary perfusion were obtained. These criteria disclosed that in cases of right ventricular hypertrophy the connective tissue of the right ventricular myocardium was increased only at high values of the insufficiency indices. On the other hand in cases of left ventricular hypertrophy the morphological features of decreased perfusion of the right ventricle were observed at low index values. In all three groups the increased vulnerability of the left ventricle to failure of coronary perfusion was numerically proved.

Adult↗
PubMedDate not supplied

Function and energy metabolism of isolated rats hearts as influenced by Sr++.

Effects of Sr++ and isoproterenol were studied in rat hearts perfused with red cell containing media. Sr++ in the presence of Ca++ causes a positive inotropic effect without corresponding metabolic changes. Without Ca++ 0.5 mM Sr++ causes an immediate arrest, 2 mM Sr++ a complete contracture (14 min) and 5 mM a contracture after about 44 min. At a level of 10 mM Sr++ phasic contractions are maintained (60 min). Occurring phasic contractions are prolonged 3 to 6fold. Administration of isoproterenol (ISO) at a level of 0.5 mM Sr++ causes a delayed occurrence of cardiac arrest and incomplete contracture. At a concentration of 2 and 5 mM Sr++ positive inotropic responses proceed to a contracture (7 min, 50 min resp.). VO2 is reduced by 0.5 mM Sr++ initially by 2 mM Sr++ with delay. 5 and 10 mM Sr++ induce an initial increase. Subsequent decrease is smallest at 10 mM Sr++ ISO at all Sr++ concentrations induces an increase in VO2 initially and strong reduction finally. During 10 min administration, high energy phosphate stores (HEP) are reduced at all Sr++ concentrations, but to the smallest extent at 10 mM Sr++, ISO at levels of 0.5 and 2 mM Sr++ induces a partial recovery of HEP, but at 5 and 10 mM a further reduction. Finally, under the influence of ISO the metabolic state is similar to that without ISO. Sr++ at high concentrations in absence of Ca++ seems to be capable of substituting in principle for Ca++ also concerning metabolism. Severe metabolic disturbances at low Sr++ concentrations indicate a failure of regulation of oxidative phosphorylation.

Adenosine Diphosphate↗
PubMedDate not supplied

Impaired tactile pattern recognition in the early stage of primary degenerative dementia compared with normal aging.

Tactile pattern recognition of ten different patterns which were engraved upon 4 x 4 cm plastic plaquettes with one hand and thereafter drawing with the other or the same hand was tested in 21 patients with a mild stage primary degenerative presenile onset dementia of Alzheimer type (DAT) and in 14 patients with a questionable dementia on the background of a chronic cardiovascular disease (CVD) in comparison to 15 healthy subjects of the same age (51 years old, elder controls, (EC)) and 16 younger subjects (22 years old, younger controls, (YC)). Patients made about four times more errors than the EC group. Duration from the begin of touching to the end of drawing was significantly longer in patients than in controls. In a second task the subjects had to recognize four subsequent patterns, then to perform a standard multiplication task and afterwards to draw all four patterns in their correct sequence. Patients made about ten times more errors in pattern recognition and series reproduction than age-matched controls.

Journal Article↗
PubMedDate not supplied

Clinical experience with temporary vena caval filters.

PURPOSE: To look at the benefits and complications of different vena caval filters inserted prophylactically. Three temporarily implantable caval filter systems were used in 67 patients. MATERIALS AND METHODS: Twelve Cook filters (six transjugular, six transfemoral), 11 Angiocor filters (one transjugular, 10 transbrachial), and 44 Antheor filters (three transjugular, four transfemoral, 37 transbrachial) were successfully implanted. In known iliac vein or caval thrombosis, the prophylactic filters were placed during thrombolytic therapy in 46 cases, surgery in 17 cases, thrombosis in pregnancy in three cases, and high-dose heparinization without lysis in one case. RESULTS: One patient had a fatal pulmonary embolism during treatment; seven thrombi were detected in the filter. Other complications were caused either by the underlying therapy alone (one fatal outcome of abdominal aorta aneurysmal surgery, two cases of cerebral hemorrhage, two cases of retroperitoneal hematomas, two cases of streptokinase fever reactions, one compartment syndrome, two cases of macrohematuria), by the combination of therapy and caval filter implantation (three cases of groin hematomas, three cases of arm hematomas), or by filter implantation alone (two cases of subclavian vein thrombosis, one catheter infection, one dislocation, one air embolism, one basket rupture). The bleeding complications were related to the aggressive thrombolytic therapy and would have occurred without filter implantation. CONCLUSION: Because temporary caval filters have no long-term complications per se, their use seems sensible as long as there are stringent indications, including the presence of iliac vein or caval thrombosis and risk of thrombus mobilization. The Antheor filter system was the most convenient system for implantation.

Adolescent↗
PubMedDate not supplied

[Water jet discotomy with microinvasive approach--in vitro testing and initial clinical aspects of a new procedure].

AIM: The difference in consistence of the nucleus pulposus and the annulus fibrosus allows the water jet to selectively remove the nucleus in a closed vertebral disc at a certain pressure range. The aim of the study was to investigate the use of water jet cutting in microinvasive spinal surgery. METHODS: A comparison in terms of efficiency between the water jet and those of the laser and APLD (automatic percutaneous lumbar discotomy) was achieved by plastic reconstruction of the resected spaces using the in-vitro-model of the spinal column of young pigs. The in-vitro-study was followed by a prospective clinical study with 21 patients. RESULTS: The in-vitro-employment of the three different methods showed that there were no significant differences in volume of the removed nucleus material. During the use of the hydro jet at 50 bar and simultaneous suction the intradiscal pressure measured in vitro remained below 1 bar. Clinical tests on the 21 patients showed good to very good results in 71% of the patients tested (mean follow-up 5.8 months). No complications were found. As working mechanism the pure mechanical effect and the influence on chemical processes within the nucleus remain points for discussion. CONCLUSION: The current studies results demonstrate that hydrojet spinal surgery might be a safe new method for surgery of disc protrusion and contained prolapse.

Adult↗
PubMedDate not supplied

[A case of bilateral isolated talonavicular synostosis in childhood--observations of tarsal joint function and functional adaptation of the proximal ankle joint].

A rare case of bilateral isolated coalition of the talonavicular joint with ball and socket ankle joint is presented. Range of motion of the subtalar joint and hindfoot mobility were measured intraoperatively. The following conclusions may be drawn on development and function of the ankle joint complex: Isolated talonavicular synostosis in the growing foot results in marked impairment of subtalar range of motion. The development of a ball and socket ankle joint may be caused thereby, if tarsal hypomobility becomes effective at an early stage of growth.

Ankle Joint↗
PubMedDate not supplied

Studies of the influence of ochratoxin A on immune and defense reactions in the mouse model.

In the mouse model, the mycotoxin ochratoxin A has a non-selective suppressive effect on various immune and defence reactions. Apart from weight depression, lymphopenia, neutrophilia and eosinophilia, antibody-producing cells, antibody titres in blood serum and phagocytosis of Escherichia coli by blood phagocytes become suppressed. Moreover, immunized animals show a lower survival rate after experimental infection with Pasteurella multocida as well as an increase in oxygen radicals in blood cells.

Animals↗
PubMedDate not supplied

Investigation of the stability of coated titanium microparticles used in sunscreens.

Due to its UV-light-absorbing properties, titanium dioxide is used in many sunscreen products. However, concern has been raised about a possible photocatalytic activity of titanium dioxide on living tissues. To reduce potential adverse effects, titanium dioxide used in cosmetic preparations is often coated. The coating should be stable under conditions of use. In order to verify the coating stability, sunscreen-grade-coated titanium microparticles were investigated by laser-induced plasma spectroscopy. No changes in the mechanical stability of the coated microparticles could be detected during the manufacturing and penetration of the sunscreen. Applying strong forces on the microparticles by centrifugation, exceeding by far in use conditions, resulted only in small changes in the coating.

Aluminum↗
PubMedDate not supplied

Influence of the antiseptic agents polyhexanide and octenidine on FL cells and on healing of experimental superficial aseptic wounds in piglets. A double-blind, randomised, stratified, controlled, parallel-group study.

The main target of the combination of octenidine with phenoxyethanol (Octenisept) is the antisepsis of acute wounds, whereas polyhexanide combined with polyethylene glycol in Ringer solution (Lavasept) is the agent of choice for antisepsis of chronic wounds and burns. Because comparative data for both agents on the effects on wound healing are lacking, we investigated the influence of preparations based on polyhexanide and octenidine versus placebo (Ringer solution) in experimental superficial aseptic skin wounds (n = 108) of 20 mm diameter, using a double-blind, randomised, stratified, controlled, parallel-group design in piglets. Computerised planimetry and histopathological methods were used for the assessment of wound healing. Histologically, no significant differences could be verified at any time between the 3 groups. However, in the early phase (day 9 after wounding), the octenidine-based product retarded wound contraction to a significantly greater extent than placebo and polyhexanide, whereas in the later phase (days 18 and 28), polyhexanide promoted contraction significantly more than did placebo and octenidine. The consequence is complete wound closure after 22.9 days using polyhexanide, in comparison to the placebo after 24.1 days (p < 0.05) and octenidine after 28.3 days (no statistical difference to placebo). This may be explained by the better tolerance of polyhexanide in vitro, which was demonstrated with dose and time dependence in cytotoxicity tests on human amnion cells.

Animals↗
PubMedDate not supplied

cAMP-dependent protein kinase activity in yeast mitochondria.

Two different cAMP-binding proteins have been identified in yeast mitochondria by photoaffinity labelling and based on the occurrence of cAMP-binding activity in two different sub-mitochondrial fractions. One protein (Mr 45-46,000) is tightly bound to the inner mitochondrial membrane whereas the other (Mr 42,000) is found in the soluble intermembrane space. With endogenous substrate cAMP-dependent protein kinase activity could not be demonstrated with sufficient clarity. However, using acidic heterologous substrates, like casein and phosvitin, one cAMP-dependent protein kinase was identified in the intermembrane space. Only low phosphate incorporation was found using histone fractions as substrate. cAMP-dependent modification of proteins appears to be very shortlived in mitochondria. Its physiological significance remains unknown, since neither mitochondrial transcription, translation, respiration nor import of cytoplasmically synthesized precursors into mitochondria appear to be influenced by exogenous cAMP either in vivo or in vitro. It is shown that cAMP is not actively transported into the inner mitochondrial compartment but rather binds to a receptor(s) localized outside the permeability barrier provided by the inner membrane.

Centrifugation, Density Gradient↗