PubMed Health⌕ Search

Biomedical subjects

U Müller

Publications and source records attributed to U Müller.

At least 235 records · Page 13Linked to original sources
PubMed1996

Inhibition of nitric oxide synthase impairs a distinct form of long-term memory in the honeybee, Apis mellifera.

Nitric oxide has been shown to be implicated in neural plasticity that underlies processes of learning and memory. In the honeybee, studies on the role of nitric oxide in associative olfactory learning reveal its specific function in memory formation. Inhibition of nitric oxide synthase during olfactory conditioning impairs a distinct long-term memory that is formed as a consequence of multiple learning trials. Acquisition or retrieval of memory or memory formation induced by a single learning trial is not affected by blocking of nitric oxide synthase. This finding provides a first step toward dissection of molecular mechanisms involved in memory formation, in general, and the special function of nitric oxide synthase in particular.

Animals↗
PubMed1996

Behavioral, neural and cellular components underlying olfactory learning in the honeybee.

A top-down approach as applied to learning and memory in honeybees provides the opportunity of relating different levels of complexity to each other, and of analyzing the rules and mechanisms from the viewpoint of the respective next higher level. Olfactory conditioning of harnessed bees exemplifies essential elements of associative learning and, in general, forms a bridge between the systems and the cellular levels of analysis. Intracellular recordings of identified neurons during olfactory conditioning play a key role in this effort. They allow testing of the assumptions made by modern behavioral theories of associative learning and provide access to cellular and molecular studies, owing to the identification of their transmitters and the peculiarities of the connectivities. Analysis at this intermediate level of complexity is particularly profitable in the bee, because essential neural elements of the associative network are known and can be tested during ongoing learning behavior. In this respect, the honeybee offers unique properties for the building of bridges between the molecular, cellular, neuronal, network and behavioral levels of associative learning.

Animals↗
PubMed1996

Honeybee venom allergy: immunoblot studies in allergic patients after immunotherapy and before sting challenge.

By immunoblot techniques, detailed antibody studies were performed with sera of 20 honeybee-venom-allergic patients during or at the end of specific immunotherapy (median duration: 3 years) and before honeybee sting challenge. Before immunotherapy, all patients had experienced systemic allergic reactions to a honeybee sting, with a mean severity of 3.5 +/- 0.5 according to the Müller classification. After the sting challenge, 10 patients (reactors) reacted again with a systemic allergic reaction, whereas 10 patients (nonreactors) did not. No differences were observed between reactors and nonreactors in total serum IgE and specific IgE to honeybee venom at the time of challenge. For immunoblot, honeybee venom (RELESS) was separated on 7.5-20% SDS-PAGE. For detection of specific IgE, IgG, IgG1, IgG4, and IgM, an alkaline phosphatase-linked second antibody was used. Both groups showed 11 antibody-binding bands: at 52, 46, 40, 31, 18.7, 16.9, 13, 11, 10, 9, and 8 kDa; however, the antibody-binding pattern was individual. The reactors differed from nonreactors in showing intense IgE and less IgG4 binding to at least one single component of the venom extract. For nonreactors, the inverse relationship was observed. The hypothesis, "intensity of IgE > or = IgG4 leads to allergic symptoms", was highly significant (P = 0.00026; chi-square). These immunoblot findings could offer predictive value in distinguishing reactors from nonreactors.

Adolescent↗
PubMed1996

Low-density lipoprotein apheresis versus lipid lowering drugs in the treatment of severe hypercholesterolemia: four years' experience.

Elevated lipoprotein concentrations seem to be linked strongly in a dose dependent manner to an increased incidence of atherosclerosis. A total of 47 patients suffering from severe hyperlipidemia were matched to treatment with LDL apheresis (Baxter, Kaneka, Lipopak; 24 patients, aged 50.2 + or - 11.5 years), diet, and/or lipid-lowering drugs or with diet and lipid-lowering drugs only (23 patients, aged 48.8 + or - 11.8 years). After treatment periods of 49.8 + or - 13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 + or - 15.1 months (drug group), the ensuing results revealed significant differences (p < 0.0001): -47.3% versus -12.1% for total cholesterol, -46.9% versus -21.8% for LDL, +8.4% versus +0.9% for HDL, -52.0% versus -13.1% for the LDL/HDL ratio, -36.4% versus - 16.2% for triglycerides, and -25.9% versus + 1.5% for lipoprotein (a). In the apheresis group, one patient died of myocardial infarction; in the drug group, there was one nonfatal myocardial infarction and the manifestation of coronary heart disease in 3 cases. There were no severe side effects in either group. All patients in the apheresis group responded to therapy. The present trial suggests that a continuing reduction in serum lipid concentrations may lower, in a dose dependent manner, the risk for development and progression of coronary heart disease. Regarding clinical and laboratory results, LDL apheresis seems to be safe, effective therapy for treatment of severe hyperlipidemia.

Adolescent↗
PubMed1996

Assignment of genes encoding GABAA receptor subunits alpha 1, alpha 6, beta 2, and gamma 2 to a YAC contig of 5q33.

A gene cluster consisting of the four gamma-aminobutyric acidA (GABAA) receptor subunit genes GABRA1, GABRA6, GABRAB2, and GABRG2 was assigned to a yeast artificial chromosome (YAC) contig of 5q33. Two of the 26 YACs of the contig are positive for all four subunit genes. The order of the GABR subunit genes with respect to known anonymous gene loci is cen-D5S380 - D5S403 - D5S529 - GABRB2 - GABRA1/A6 - GABRG2-D 5S422-tel. This novel YAC contig lies between known YAC contigs of 5q34/q35 and 5q31-q33.

Chromosome Banding↗
PubMed1996

Apolipoprotein E epsilon 4 allele, cognitive decline, and deterioration of everyday performance in Alzheimer's disease.

Many studies have demonstrated an association between the apolipoprotein E (apoE) epsilon 4 allele and Alzheimer's disease (AD). The present study is concerned with the relationship between the apoE epsilon 4 allele and the progression of symptoms in AD. We determined rates of cognitive decline and deterioration in everyday performance prospectively over 3 years in 64 patients with clinically diagnosed AD using the Cambridge Cognitive Examination (CAMCOG), the Mini-Mental State Examination (MMSE), and the Dementia Scale (DS) included in the Cambridge Mental Disorders of the Elderly Examination (CAMDEX). Carriers and noncarriers of the epsilon 4 allele did not significantly differ in cognitive functioning and everyday performance at baseline measurements. The time that had elapsed since the estimated onset of symptoms was also not different between the two groups. This suggested that the clinical progression of AD was not associated with the epsilon 4 status before the patients entered the study. On prospective observation, the rate of cognitive decline assessed with the CAMCOG and the MMSE and the rate of deterioration in everyday performance rated with the DS were also not different between carriers and noncarriers of the epsilon 4 allele. We conclude that the clinical course of AD is independent of the apoE epsilon 4 allele.

Age of Onset↗
PubMed1996

Lack of association between alpha 1-antichymotrypsin polymorphism, Alzheimer's disease, and allele epsilon 4 of apolipoprotein E.

We investigated the possibility that a polymorphism of alpha 1-antichymotrypsin modifies the risk for Alzheimer's disease (AD). Testing 147 AD patients and 74 controls, we did not find evidence of an association between alpha 1-antichymotrypsin polymorphism and AD and also failed to detect a modifying effect of this polymorphism in patients carrying at least one epsilon 4 allele of apolipoprotein E.

Alleles↗
PubMed1996

B2 bradykinin receptors in cultured neonatal rat cardiomyocytes mediate a negative chronotropic and negative inotropic response.

Receptors for bradykinin (BK) were characterized in primary cultures of beating neonatal rat cardiomyocytes using [3H]BK was radioligand. Degradation studies demonstrated that [3H]BK was stable for at least 2 h when incubated with cardiomyocytes at 2 and 37 degrees C in the presence of bacitracin in combination with captopril or ramiprilat. Without these inhibitors, > 80% of the [3H]BK was degraded within 2 h at 37 degrees C. This indicates that angiotensin-converting enzyme (ACE) is responsible for the main BK-degrading activity in cardiomyocytes. Scatchard plots were linear and gave a Kd of 1.5 +/- 0.8 nmol/l (mean +/- SD, n = 4) and a maximum binding capacity of 55-125 fmol/mg protein. Association and dissociation studies showed that binding of [3H]BK was saturable and reversible. Binding of [3H]BK at 37 degrees C led to internalization of the ligand. Competition studies with B1 and B2 agonists and antagonists were consistent with a B2 subtype of receptor. Addition of BK to beating cardiomyocytes (> 1 nmol/l) at 37 degrees C gave a strong but transient negative chronotropic effect. This response was paralleled by changes in the pulsation amplitude, which indicated a simultaneous negative inotropic effect of BK. These results provide a basis for the hypothesis that ACE inhibition exerts its cardioprotective effect at the level of a population of cardiomyocytes by virtue of kinin receptor-mediated mechanisms.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

A three-year clinical investigation into efficacy, cycle control and tolerability of a new low-dose monophasic oral contraceptive containing gestodene.

This long-term, open-label multicenter study investigated the clinical efficacy and tolerability of a monophasic oral contraceptive containing 20 micrograms ethinylestradiol and 75 micrograms gestodene. A total of 670 women between the ages of 18 and 45 years received the trial preparation over a 3-year period, giving 19,095 evaluable cycles. Of the 670 participants in the study, 75% completed at least 24 cycles with the trial preparation and 46% remained in the study for the full 3 years. One pregnancy occurred during the study which was considered by the investigator to be the result of misuse of the drug, giving an uncorrected Pearl Index of 0.07. Cycle control with the trial preparation was good, especially in women who did not miss any pills. By cycle 3, only 10.2% of women who had not missed pills reported intermenstrual bleeding (scanty or medium/excessive bleeding) and this decreased to 2.3% by cycle 36. The preparation was well tolerated, with a low incidence of unprompted adverse events. There were no clinically significant changes in mean body weight or blood pressure. Over the 3 years of the study, 10% of women withdrew from the study for reasons related mostly to mild adverse events. Results from this study demonstrate that the trial preparation is a reliable and well-tolerated oral contraceptive that provides good cycle control.

Adolescent↗
PubMed1996

[Organochlorine pesticide residues in cow's milk, Nicaragua].

This work reports on a preliminary study carried out in Nicaragua to build a profile of the contamination of cow's milk with 10 organochlorine pesticides and make recommendations based on the findings. Between December 1993 and March 1994, milk samples were collected from 48 different sites in the country. The samples were analyzed for residues of hexachlorobenzene (HCB), alpha-BHC, lindane, aldrin, dieldrin, oxychlordane, heptachlor epoxide, and the principal metabolites of DDT (p,p'-TDE, p,p'-DDE, and p,p'-DDT) by means of solid-phase extraction from milk fat, and the quantity of the residues was determined by gas chromatography with electron capture detection. Heptachlor epoxide was found in 1 milk sample, dieldrin in 1, lindane in 3, oxychlordane in 3, alpha-BHC in 3, aldrin in 6, HCB in 9, and metabolites of DDT in 39 (81% of the samples). The six samples most heavily contaminated with by-products of DDT came from the departments of León and Chinandega, in the Pacific region, where there used to be intensive cotton production. The highest concentration was found in the sample from Malpaisillo, with 1105 micrograms of pesticide per kg of milk fat. The authors recommend that studies should be done so that the risk of contamination of other food products can be estimated, and that the public's health should be protected through strict control of the production or importation, storage, sale, and use of organochlorine pesticides.

Animals↗
PubMed1996

[Psychiatric sequelae of craniocerebral trauma--a review of the literature].

In a brief review psychiatric aspects of head-injured patients are discussed. The topic is put into a historical perspective. Examples of recent developments in head-trauma research are given. Differentiation between focal and diffuse brain injury is suggested to be of clinical relevance. Little is known as yet about the neuropsychologic and psychiatric sequelae of diffuse axonal injury to the brain.

Brain Concussion↗
PubMed1995

[Heparin-induced thrombocytopenia. Results from the Comprehensive Hospital Drug Monitoring (CHDM) Bern/St. Gallen].

Of 23,520 consecutive hospitalizations from 1980-1988 (corresponding to 16,628 individual patients) in three departments of general internal medicine, 8261 were treated with heparin. All observations of patients displaying a probable, possible or questionable relationship of thrombocytopenia to heparin (administered i.v. or subcutaneously) were electronically collected by the CHDM program, revised on the basis of the primary case records and selected by standardized criteria. 13 of the 8261 patients exposed to heparin were considered to have a probable or possible HIT, corresponding to a frequency of 0.157%. In two of them severe thrombocytopenia was observed (corresponding to 0.024%) accompanied in one case by a white clot syndrome. Thrombocytopenia was defined as a platelet value below 100 x 10(9)/l and severe thrombocytopenia as one below 30 x 10(9)/l. In the literature we found slight, asymptomatic thrombocytopenia in < or = 1-8% of heparin treated patients. Our result of 11 out of 8261 (corresponding to 0.133%) is low, partly because the thrombocyte count was not controlled systematically, the heparin used was mainly produced from swine intestinal mucosa, and no antibody tests had been carried out. To prevent severe thrombocytopenia from heparin we propose monitoring the platelet count if the treatment is to be continued for more than 5 days. The newer low molecular weight heparins, all of swine origin, are much safer compared to the traditional preparations in regard to risk of HIT and white clot syndrome.

Aged↗
PubMed1995

The nitric oxide/cGMP system in the antennal lobe of Apis mellifera is implicated in integrative processing of chemosensory stimuli.

The high concentration and the localization of nitric oxide synthase in the olfactory system of both vertebrates and invertebrates suggest that the diffusible messenger nitric oxide plays a central role in the processing of chemosensory information. This paper describes the nitric oxide releasing system in the antenna and the antennal lobes of Apis mellifera using the NADPH diaphorase technique, and analyses the contribution of the nitric oxide system in the neuronal processing of chemosensory signals using a behavioral assay in vivo. In the antenna the strongest NADPH diaphorase staining is found in non-neuronal auxiliary and/or epithelial cells, while the sensory cells and the antennal nerve are stained at a low level. At the major site of chemosensory signal integration, the antennal lobes, the highest nitric oxide synthase activity is located in the glomeruli, which are ideally suited to act as diffusion compartments. We demonstrate that inhibition of nitric oxide synthase in the antennal lobes specifically interferes with neuronal processing of repetitive chemosensory stimuli but does not affect the response to single stimuli, and is independent of parameters such as satiation level, stimulus strength, interstimulus interval and duration of sensory stimuli. Since inhibition of the soluble guanylate cyclase, a major target of nitric oxide, also particularly affects the adaptive component, the physiological effects of nitric oxide appear to be mediated by the action of cGMP. These findings suggest that the nitric oxide/cGMP system in the antennal lobes is a component of the molecular machinery involved in adaptive and/or integrative mechanisms during chemosensory information processing in vivo.

Animals↗
PubMed1995

Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA.

Deficiency in monoamine oxidase A (MAOA), an enzyme that degrades serotonin and norepinephrine, has recently been shown to be associated with aggressive behavior in men of a Dutch family. A line of transgenic mice was isolated in which transgene integration caused a deletion in the gene encoding MAOA, providing an animal model of MAOA deficiency. In pup brains, serotonin concentrations were increased up to ninefold, and serotonin-like immunoreactivity was present in catecholaminergic neurons. In pup and adult brains, norepinephrine concentrations were increased up to twofold, and cytoarchitectural changes were observed in the somatosensory cortex. Pup behavioral alterations, including trembling, difficulty in righting, and fearfulness were reversed by the serotonin synthesis inhibitor parachlorophenylalanine. Adults manifested a distinct behavioral syndrome, including enhanced aggression in males.

Aggression↗
PubMed1995

Theiler's virus infection of 129Sv mice that lack the interferon alpha/beta or interferon gamma receptors.

The Daniels strain of Theiler's virus causes a persistent infection of the white matter of spinal cord of susceptible mice, with chronic inflammation and primary demyelination. Inbred 129Sv mice are resistant to this infection; they present with mild encephalomyelitis and clear the infection within a matter of days. A very different outcome was observed with inbred 129Sv mice whose receptors for interferon alpha/beta or interferon gamma had been inactivated by homologous recombination. The former presented severe encephalomyelitis with acute infection of neurons, particularly in brain and hippocampus, and extensive infection with necrosis of the choroid plexus. Most animals died of this acute disease. The latter, presented the same early encephalomyelitis as the control 129Sv mice. However, they remained persistently infected and developed a very severe late infection of the white matter with extensive primary demyelination. This late disease looked like an exacerbated form of the chronic demyelinating disease observed in susceptible inbred mice such as the SJL/J or FVB strains. Our results show that the two interferon systems play nonredundant roles in the resistance of the 129Sv mouse to the infection by Theiler's virus. They also lend support to the notion that the Ifg gene is involved in the resistance/susceptibility of inbred strains of mice to persistent infection by this picornavirus.

Animals↗
PubMed1995

Activation of (R)-2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans.

(R)-2-Hydroxyglutaryl-CoA dehydratase (HgdAB) from Acidaminococcus fermentans catalyses the reversible dehydration of its substrate to glutaconyl-CoA. The enzyme has to be activated by ATP, MgCl2, and Ti(III)citrate by an activator protein (HgdC) that is present in the organism at very low concentrations. Cell-free extracts of a recombinant Escherichia coli strain, in which hgdC was expressed, contained the activator with a specific activity of up to 45 U'/mg protein (1 U' is the amount of activator required to generate 1 U dehydratase activity under standard assay conditions). The recombinant protein was purified 44-fold to a specific activity of 2000 U'/mg. It is a homodimer (gamma 2, 54 kDa) and contains 4 mol non-heme iron and 3 mol inorganic sulfur. Under air, the activator has a half-life of seconds and even under strict anaerobic conditions it is very unstable. The amino acid sequence of the activator shows similarities to the ATP-binding motifs of several kinases. The dehydratase component was purified from its natural source revealing a heterodimer (alpha beta, 100 kDa) that contains 4 mol non-heme iron, 4 mol inorganic sulfur, 0.3 mol riboflavin, and 1 mol FMN. A mechanism is proposed in which an iron-sulfur cluster or a flavin donates one electron to the thiolester of the substrate (R)-2-hydroxyglutaryl-CoA. The resulting ketyl may eliminate the adjacent hydroxyl group yielding an enoxy radical from which the beta-hydrogen is abstracted as a proton leading to the ketyl of glutaconyl-CoA. In the final step, the latter is oxidized to the product, whereby the reduced enzyme is regenerated. It is suggested that during the activation step, the electron of this cycle is fed into the enzyme by Ti(III)citrate and energized by hydrolysis of ATP; both functions are apparently catalysed by the activator. The enzyme remains in this activated state for several turnovers, which may explain the requirement of only catalytic amounts of ATP and substoichiometric amounts of activator (dehydratase/activator ratio approximately 200:1). The oxidants 4-nitrobenzoate, 2-nitrophenol, 3-nitrophenol, 4-nitrophenol, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone or chloramphenicol (all at concentrations greater than or equal to 1 microM) may trap this electron resulting in a reversible, transient inactivation of the dehydratase.

Adenosine Triphosphate↗