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Biomedical subjects

D Müller

Publications and source records attributed to D Müller.

At least 145 records · Page 8Linked to original sources
PubMed1998

[A totally implantable hearing aid for inner ear deafness: TICA LZ 3001].

Recently, Zenner et al. implanted the first totally implantable electronic hearing devices in patients with SNHL (HNO 46 [1998] 844-852). In the present report, technical and audiological features of the implant TICA are published. The development of the piezoelectric transducer and the microphone for implantation in the posterior wall of the auditory canal as components for the present fully implantable hearing system has already been described (HNO 45, 1997, 792-880). Here we report about our experience with the electronic main module that completes the TICA LZ 3001 system. This module is suited for implantation in the mastoid bone and contains the signal-processing electronics and an integrated battery that can be recharged transcutaneously with a portable charger. The recharging time is around 2 h for an implant operating time of 50 h. The microphone and transducer connectors allow for easy replacement of the main module when the battery lifetime is reached. This lifetime is around 3-5 years. A small wireless remote control allows volume adjustment, contains an on/off switch, and permits selection of four different individual hearing programs. The basic audiological features are provided by a flexible, digitally programmable 3-channel-AGC-system with a peak clipping function. The total bandwidth is around 10 kHz. To our knowledge this is the first fully implantable hearing system that has been in implanted in humans.

Ear Canal↗
PubMed1998

[Analysis of functional changes in ventricular late potentials for risk assessment of ventricular tachycardias after myocardial infarct].

BACKGROUND: Electrophysiological abnormalities during ischaemia and increased heart rate may influence the detection of ventricular late potentials in the surface electrocardiogram. Whether the analysis of functional changes adds information to the risk stratification of patients prone to ventricular tachycardia is unclear. METHODS: We therefore retrospectively investigated 100 selected patients (25 with documented, sustained ventricular tachycardia (< 230/min) ( = VT group), 25 resuscitated from ventricular fibrillation (VF group) and 50 without ventricular arrhythmias (phi VT/VF group)) in the chronic phase after myocardial infarction. Late potential analysis was performed at rest, during atrial pacing at a rate of 100/min and 120/min (n = 60), during and after occlusion of the coronary artery for coronary angioplasty (PTCA) (n = 70), and immediately after maximum exercise using selective signal averaging. RESULTS: At rest in 72% of patients in the VT group, in 32% of the VF group, and in 6% of the phi VT/VF group late potentials could be found. During atrial pacing in 80% of patients in the VT group, in 72% of the VF group, and in 10% of the patients in the phi VT/VF group and during ischaemia because of occluded coronary artery in 86% of patients in and the VT group, 70% of the VF group, and in 20% of the patients of the phi VT/VF group late potentials were present. Immediately after maximum exercise which let both ischaemia and increased heart rate, late potentials were detectable in 92% of patients in the VT group, 80% of the VF group, and in 14% of patients in the phi VT/VF group. Similar results could be achieved by using the Holter-ECG after exact correction of recorder tape speed variations. 62% of patients with only by ischaemia, increased heart rate or exercise provokable late potentials and all patients with preexistent not by PTCA extinguished late potentials developed recurrent ventricular tachycardias during the one year follow-up period. Patients without late potentials (n = 50) and patients with preexistent by PTCA extinguished late potentials (n = 11) had no recurrent ventricular tachycardias. Cycle length of recurrent and clinical tachycardia in patients with preexistent not by PTCA extinguished late potentials (n = 18) were significantly longer than in patients with only provokable late potentials (n = 21). CONCLUSIONS: Analysis of functional changes of ventricular late potentials with exercise or in Holter ECG recordings promises considerable improvement of postinfarction risk stratification especially in patients prone to ventricular fibrillation.

Adult↗
PubMed1998

Nephrocalcinosis in three siblings with idiopathic hypercalciuria.

Idiopathic hypercalciuria (IH) associated with nephrocalcinosis was found in three of six siblings. After the three affected children were maintained on a low-calcium diet, they demonstrated increasing hypercalciuria, parathyroid hormone, and vitamin D3 levels. An oral calcium loading test was not necessary to diagnose renal IH. During treatment with hydrochlorothiazide, the calcium excretion was normalized. These patients are remarkable because nephrocalcinosis is generally regarded as a rare complication of renal IH. Moreover, the fact that three of six siblings are affected raises the question of whether the renal form of IH is genetically distinct from other forms of IH.

Adolescent↗
PubMed1998

Lu 25-109, a combined m1 agonist and m2 antagonist, modulates regulated processing of the amyloid precursor protein of Alzheimer's disease.

To examine the effects of the combined muscarinic ml-agonist/m2-antagonist Lu 25-109 on regulated processing of the amyloid protein precursor (APP), we used both transfected cells expressing human muscarinic m1 or m2 acetylcholine receptors, and fresh rat hippocampal slices. Lu 25-109 readily stimulated APPs secretion from HEK 293 cells overexpressing m1, but not m2, receptors, as well as from the hippocampal brain slices. Time-course analyses revealed a rapid (5-35 minutes), and a delayed (55-75 minutes) secretory response to Lu 25-109 with distinct concentration profiles suggesting two distinct cell biological mechanisms. Both responses appeared to reflect post-translational mechanisms because levels of APP message were unchanged after 60 minutes of stimulation with Lu 25-109. In comparison to carbachol, Lu 25-109 had a significantly lower intrinsic activity at muscarinic m1 receptors, compatible with a pharmacological profile as a partial agonist at recombinantly expressed m1 receptors. In as much as stimulation of APPs secretion is associated with reduced formation of A beta peptides, Lu 25-109 may be useful to reduce A beta generation, and thus, slow amyloid plaque formation. Moreover, Lu 25-109 may be useful in promoting the known neurotrophic and neuroprotective biological functions of secreted APPs.

Alzheimer Disease↗
PubMed1998

Streptozotocin increases free fatty acids and decreases phospholipids in rat brain.

Streptozotocin (STZ) is a diabetogenic drug that disrupts glucose and energy metabolism in brain. To study its effect on brain lipids, tissue concentrations of free fatty acids and phospholipids were measured in the temporal cortex and the hippocampus of adult rats 3 weeks after a single intracerebroventricular (icv) injection of STZ. STZ increased concentrations of palmitic acid and stearic acid in temporal cortex and these of arachidonic acid both in the anterior part of the hippocampus and in CA1. In addition, palmitic acid and stearic acid concentrations were elevated in the anterior hippocampus. In contrast, STZ decreased brain cortex levels of phosphatidylethanolamine and phosphatidylserine. These data show that STZ alters brain lipid metabolism. They suggest that oxidative phospholipid breakdown is accelerated by STZ. These changes may be related to decreased brain glucose utilization and energy formation.

Animals↗
PubMed1998

Severe coagulopathy after a bite of a green bush viper (Atheris squamiger): case report and biochemical analysis of the venom.

A 34 year old male bitten by an adult Atheris squamiger snake developed symptoms of nausea, vomiting, diarrhea which were followed by drowsiness and impaired breathing. Local hemorrhage, edema and pain at the bite-site occurred, but no systemic bleeding or hemorrhagic diathesis developed. All clinical and laboratory parameters were in the normal range except for afibrinogenemia, thrombocytopenia and slight proteinuria. Replacement therapy (fibrinogen and platelet concentrates) and treatment of shock stabilized the patient within 2d and coagulation returned to normal. Atheris squamiger venom was subjected to biochemical and biological analysis. The LD50 of the venom was 5 mg/kg (mice, s.c.). It produced local hemorrhage corresponding to about 25% of the activity of puff adder venom (Bitis arietans). In vitro the venom had a fibrinogen-converting activity, it did not activate purified prothrombin but very likely contained a F V and Ca2+-dependent prothrombin activator. The venom exhibited strong platelet-aggregating activity, which was not inhibited by protease inhibitors and by EDTA or EGTA. The venom also aggregated acetylsalicylic acid treated platelets indicating, that the arachidonic acid pathway was not essential for activation. Rat serum rapidly inhibited the platelet-aggregating activity of the venom; human serum, however, had only a partial inhibitory effect. Preliminary experiments showed that platelet-aggregating activity may be separated from fibrinogen-converting activity by anion-exchange chromatography.

Adult↗
PubMed1998

Application of cryopreserved precision-cut liver slices in pharmacotoxicology--principles, literature data and own investigations with special reference to CYP1A1-mRNA induction.

Principle steps necessary for cryopreservation of precision-cut liver slices as currently applied by different groups are summarized including own results concerning mode of freezing. Now we use rapid freezing by immersion in liquid nitrogen after exposure to 10% DMSO as the cryoprotectant for rat liver slices. The results indicate well-maintained cytochrome P450 (CYP)-dependent deethylation rates in slice homogenate after short-term incubation. ECOD rate in intact thawed slices was even higher than in fresh ones after 2 h incubation. In contrast to fresh slices all parameters except protein content decreased to marginal levels during long-term incubation of thawed slices for 24 h. The first preliminary experiments on albumin secretion by thawed rat liver slices, measured between the 2nd and the 4th hour of incubation, showed partial maintenance of this liver specific differentiated function. Trials to induce CYP1A1 in thawed rat liver slices in vitro by beta-naphthoflavone (BNF) resulted in increased expression of CYP1A1-mRNA within 6 h as shown by RT-PCR and quantified by competitive RT-PCR. The decline of deethylation rates, determined in slice homogenates, and of viability within 24 h incubation was not prevented by exposure to BNF or DMSO. The results derived from one sample of cryopreserved human liver slices indicate a quite acceptable maintenance of function up to 6 h, if the same protocol as developed for rat liver slices was used.

Albumins↗
PubMed1998

Influence of 2-acetylaminofluorene (2-AAF) on biotransformation and lipid peroxidation in salivary glands and liver from male rats.

Salivary glands proved to be active in biotransformation. In microsomes of rat salivary glands 7-ethoxyresorufin O-deethylation (EROD) and 7-pentoxyresorufin O-depentylation (PEROD) were detectable, but with much lower activities than in the liver. Beside the well-known induction of EROD or PEROD in the liver by beta-naphthoflavone (BNF) or phenobarbital (PB), respectively, a marked rise in EROD rate of salivary glands was observed after BNF treatment. Administration of 2-AAF caused an increase in EROD rates in liver microsomes, but a decrease in microsomes of salivary glands. This decrease in EROD rate was accompanied by selective cytotoxic damages in the convoluted granulated tubules of the submandibular glands. No cytotoxic damage occurred in the submandibular glands after a combined administration of the inducer BNF and 2-AAF. This indicates relations between these toxic effects of 2-AAF and changes of 2-AAF-metabolism in BNF-induced rats, maybe in the liver and/or in the submandibular glands themselves.

2-Acetylaminofluorene↗
PubMed1998

Induction of cytochrome P450 1A1 in rat liver slices by 7-ethoxycoumarin and 4-methyl-7-ethoxycoumarin.

7-Ethoxycoumarin (EC) is widely used as a model substrate for monooxygenase function, its O-deethylation representing cytochrome P450 (P450) activity mainly of 1A but also of 2B isoforms. Reports on investigations of its own capacity to induce or suppress P450 activities, however, have not been found in biomedical literature. To avoid the influence of in vivo pharmacokinetics, studies can well be undertaken with liver slice incubation. Therefore in the present investigation precision-cut rat liver slices from male 43-63-day-old male HAN:Wistar outbred rats were incubated at 30 degrees C in carbogen saturated William's Medium E for 24 h. EC was added previously to final concentrations of 10, 25, 50, 75 or 100 microM. After incubation, homogenate was prepared from slices and used for model reactions (7-ethoxyresorufin O-deethylation [EROD] and 7-pentoxyresorufin O-depentylation [PROD]). EROD, indicating activities of 1A isoforms, was enhanced by incubation with EC at 25 and 50 microM to about doublefold but showed control or lower values at 75 and 100 microM. Incubation with beta-naphthoflavone in comparison led to variable increases (3-5-fold of controls). For PROD as an indicator of the phenobarbital inducible P450 isoforms 2B1 and 2B2 no enhancement was found, but a decrease by incubation with 75 and 100 microM EC. To further investigate the correlation between enzyme activity and gene expression after slice incubation, P450 1A1 mRNA content was measured by RT-PCR. Induced gene expression for 1A1 was seen with different EC concentrations to a variable extent, though not as strong as with BNF. Similar incubation with 4-methyl-7-ethoxycoumarin revealed an even stronger induction of EROD activity with maxima at about 10-32 microM, reaching BNF values. In contrast incubation with 7-benzyloxycoumarin had no evident inducing or suppressing effect, neither on EROD nor on PROD activity.

Animals↗
PubMed1998

Monooxygenation, cytochrome P450-mRNA expression and other functions in precision-cut rat liver slices.

Precision-cut rat liver slices (KRUMDIECK slicer, slice thickness 200-250 microm) were incubated in rollers containing modified William's medium E at 37 degrees C for 2, 24 and 48 hrs. Protein, DNA, potassium and glutathione concentrations did not decrease during 48 hrs. Lactate dehydrogenase (LDH) leakage into the medium was relatively marked during the first 2 hrs of incubation, from the 2nd to the 48th hr LDH leakage was very low. The same is true of the release of thiobarbituric acid-reactive substances. Albumin synthesis and transport into the medium decreased to about 70% after 48 hrs. Cytochrome P450 (CYP)-dependent 7-ethoxycoumarin O-deethylation rate was relatively stable up to 48 hrs, whereas testosterone hydroxylation decreased significantly without alterations of the proportions of the 7 quantified hydroxylated metabolites. After exposure of the slices to beta-naphthoflavone for 6 hrs CYP1A1-mRNA expression, measured by competitive RT-PCR, was increased by a factor of at least 1000. Precision-cut liver slices are a useful tool for the study of various hepatic functions, drug metabolism and its induction in vitro.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1998

Immunohistochemical localization of cytochrome P450 1A1 in precision-cut rat liver slices after in vitro exposure to beta-naphthoflavone.

Mono- and polyclonal antibodies have been used to study the localization and distribution of cytochrome P450 1A1 (CYP1A1) in cultured precision-cut liver slices with various immunohistochemical methods. Neither in non-incubated slices nor in slices incubated in the absence of beta-naphthoflavone (BNF) for 24 hrs was CYP1A1 immunohistochemically detectable. After incubation in the presence of BNF (25 microM), however, CYP1A1 was well visible in parenchymal and biliary epithelial cells. CYP1A1 was not evenly distributed, but was localized predominantly in hepatocyte layers near the surfaces of the slices. This distribution could be due to the preferential uptake of BNF by outer cell layers or due to functional changes of inner cells. Together with results obtained with other methods (e.g. RT-PCR) this investigation also demonstrates that precision-cut liver slices are a useful tool for the detection of in vitro induction of CYP1A1.

Animals↗
PubMed1998

Neuroborreliosis and isolated trochlear palsy.

We report here for the first time a child with isolated trochlear palsy and neuroborreliosis. IgG and IgM antibodies against Borrelia burgdorferi were highly positive in serum and cerebrospinal fluid respectively. The symptoms resolved completely after initiation of antibiotic treatment with ceftriaxone.

Antibodies, Bacterial↗
PubMed1998

Recombinant human natural autoantibodies against GPIIb/IIIa inhibit binding of autoantibodies from patients with AITP.

Autoimmune thrombocytopenic purpura (AITP) is caused by autoantibodies predominantly against platelet membrane glycoproteins (GP) IIb/IIIa and GPIb/IX. Naturally occurring autoantibodies have been described against a variety of autoantigens; it has been suggested that perturbation of their regulation may be associated with autoimmune diseases. Using a combinatorial Fab phagemid library from an individual immunized with human RhD+ red blood cells, we evaluated the presence of natural anti-GPIIb/IIIa autoantibodies as well as their relation to AITP-associated anti-GPIIb/IIIa autoantibodies. Selection on native GPIIb/IIIa and characterization of positive clones by inhibition studies against murine monoclonal anti-GPIIb/IIIa antibodies and by DNA analysis revealed the presence of two distinct recombinant anti-GPIIb/IIIa autoantibodies, which partially inhibited binding of affinity-purified platelet-associated autoantibodies from 8/12 AITP patients. Our results demonstrated that GPIIb/IIIa-specific Fab directed against conformational epitopes within the GPIIb/IIIa complex may be cloned from the genome of an individual immunized with RhD+ red blood cells, who was not affected by AITP. The partial inhibition of binding of platelet-associated autoantibodies from AITP patients to GPIIb/IIIa by the recombinant anti-GPIIb/IIIa phage clones suggests recognition of closely related antigenic epitopes. These phage clones may represent down-regulated, potentially pathological autoantibodies and could be used as new tools for investigation of AITP.

Amino Acid Sequence↗
PubMed1998

Antibodies against platelet glycoproteins and antiphospholipid antibodies in autoimmune thrombocytopenia.

Autoantibodies against platelet glycoproteins (anti-GP) are found in the majority of patients with autoimmune thrombocytopenia (AITP) as well as in thrombocytopenia associated with systemic lupus erythematosus (SLE). Some of these patients may have anti-phospholipid antibodies (anti-PL). To evaluate the pathogenetic significance of anti-PL and anti-GP antibodies in AITP and SLE patients, we investigated anti-cardiolipin (anti-CL), anti-phosphatidylserine (anti-PS) and anti-GP antibodies (anti-GPIIb-IIIa and anti-GPIb-IX) in 71 patients with AITP and 3 thrombocytopenic patients with SLE. Anti-GP antibodies were detected in 52 (70%) patients. Fifty-six (73%) patients showed anti-PL antibodies. Seven patients (6 AITP, 1 SLE) with both anti-GPIIb-IIIa and IgG anti-PL antibodies were followed during treatment with corticosteroids. Antibodies were measured before treatment and at the time of platelet-peak. Anti-GPIIb-IIIa antibodies decreased in all or became undetectable in five. In contrast, IgG anti-PS and IgG anti-CL antibodies decreased only moderately or remained positive. Adsorption experiments, using gelfiltered platelets, erythrocyte (Ec)-inside-out-vesicles and purified GPIIb-IIIa, showed that anti-GP and anti-PL antibodies have distinct specificities and do not crossreact. We conclude that anti-PL and anti-GP antibodies may be present simultaneously in some patients with immune mediated thrombocytopenia. Although anti-PS as well as anti-CL antibodies may be responsible for thrombocytopenia, we speculate that anti-GPIIb-IIIa antibodies are more related to the severity of thrombocytopenia.

Adolescent↗
PubMed1998

Plasma autoantibodies against platelet glycoprotein IIb/IIIa from patients with autoimmune thrombocytopenic purpura may recognize different antigenic determinants.

Autoantibodies against platelet glycoprotein (GP) GPIIb/IIIa have been demonstrated in patients with autoimmune thrombocytopenic purpura. Recently, it has been shown that plasma autoantibodies from some patients bind to the cytoplasmic domain of GPIIIa. Our aim was to evaluate further the binding specificity of these plasma autoantibodies. From 7 patients with detectable plasma antibodies against intact GPIIb/IIIa, 1 showed strong antibody binding to a synthetic C-terminal peptide of GPIIIa. Ig class analysis of affinity purified anti-GPIIb/IIIa autoantibodies from this patient revealed an IgM antibody that reacted with intact GPIIb/IIIa as well as with recombinant GPIIb/IIIa lacking the C-terminal domains, and an IgG antibody that bound to intact GPIIb/IIIa but not to GPIIb/IIIa lacking the C-terminal region. These data indicate that this patient has at least 2 autoantibodies, an IgG directed against the cytoplasmic domain of GPIIIa and an IgM reacting with the extracellular part of GPIIIa. This may support the hypothesis that plasma IgG antibodies directed against the C-terminal domain of GPIIIa may be due to the exposition of cytoplasmic epitopes of GPIIIa as a result of increased cell lysis by IgM autoantibodies.

Antibody Specificity↗
PubMed1998

Degradation of chloroaromatics: purification and characterization of a novel type of chlorocatechol 2,3-dioxygenase of Pseudomonas putida GJ31.

A purification procedure for a new kind of extradiol dioxygenase, termed chlorocatechol 2,3-dioxygenase, that converts 3-chlorocatechol productively was developed. Structural and kinetic properties of the enzyme, which is part of the degradative pathway used for growth of Pseudomonas putida GJ31 with chlorobenzene, were investigated. The enzyme has a subunit molecular mass of 33.4 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Estimation of the native Mr value under nondenaturating conditions by gel filtration gave a molecular mass of 135 +/- 10 kDa, indicating a homotetrameric enzyme structure (4 x 33.4 kDa). The pI of the enzyme was estimated to be 7.1 +/- 0.1. The N-terminal amino acid sequence (43 residues) of the enzyme was determined and exhibits 70 to 42% identity with other extradiol dioxygenases. Fe(II) seems to be a cofactor of the enzyme, as it is for other catechol 2,3-dioxygenases. In contrast to other extradiol dioxygenases, the enzyme exhibited great sensitivity to temperatures above 40 degrees C. The reactivity of this enzyme toward various substituted catechols, especially 3-chlorocatechol, was different from that observed for other catechol 2,3-dioxygenases. Stoichiometric displacement of chloride occurred from 3-chlorocatechol, leading to the production of 2-hydroxymuconate.

Amino Acid Sequence↗