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P Mayer

Publications and source records attributed to P Mayer.

At least 19 recordsLinked to original sources
PubMed2001

Distribution of G-protein-coupled receptor kinase (GRK) isoforms 2, 3, 5 and 6 mRNA in the rat brain.

There is limited knowledge about the distribution of the different G-protein-coupled receptor kinases (GRKs) in the rat brain, especially for the recently cloned isoforms GRK5 and GRK6. In this work an overview will be given of the mRNA expression patterns of four G-protein-coupled receptor kinases, GRK2 (betaARK1), GRK3 (betaARK2), GRK5 and GRK6 in the rat brain. As now shown by us and recently by others GRK2 and GRK3 are widely distributed in rat brain with nearly the same expression pattern. But GRK3, in general, appeared to be weaker expressed than GRK2 in most brain areas. Exceptions were the islands of Calleja, the compact part of the substantia nigra and the locus coeruleus. GRK3 mRNA was very low expressed or absent in the striatum and in some hypothalamic and thalamic nuclei. The expression pattern of GRK6 was also similar to GRK2. In the caudate putamen GRK6 yielded the strongest hybridization signal of all GRK types. GRK5 took a special position. The message for this form was not expressed ubiquitously in the brain but was mainly localized in limbic brain regions with a very prominent expression in the lateral septal area. GRK5 may therefore be involved in reward and addiction. Accordingly, a higher expression level of GRK5 mRNA was found in the lateral septum of cocaine-sensitized rats as compared to controls.

Animals↗
PubMed2001

Regulation of mu-opioid receptor gene transcription by interleukin-4 and influence of an allelic variation within a STAT6 transcription factor binding site.

Morphine and the endogenous opioid peptide beta-endorphin exert neuromodulatory as well as immunomodulatory effects, which are transduced by mu-opioid receptors. In this report we show that stimulation with interleukin-4 induces mu-opioid receptor transcripts in human primary blood cells (T cells and polymorphonuclear leukocytes), immune cell lines (Raji, U-937, and HMEC-1), and dendritic cells. In nonstimulated immune cells this gene is silent. In addition, mu receptor transcription is up-regulated by interleukin-4 in cultures of primary rat neurons. Transient transfection experiments in Raji and SH SY5Y neuronal cells with human and rat reporter gene constructs linked the interleukin-4 effect directly to cis-active mu receptor promoter elements located at nucleotide -997 on the human gene and nucleotide -727 on the rat gene. The interleukin-4 response elements function orientation independently. They bind STAT6 transcription factors as shown by electrophoretic mobility shift assays. In the human gene, a single nucleotide polymorphism within the interleukin-4 response element reduces the trans-activating potential of this element by 50%, which may affect the phenotype of persons carrying this variation. These findings provide a molecular basis for understanding bidirectional interactions between the opioid system and the immune system.

Alleles↗
PubMed2001

Spectroscopic and structural studies on polyfluorophenyl tellurides and tellurium(IV) dihalides.

Bis(fluorophenyl) tellurides R2Te (R = C6F2H3 (1), CF3C6F4 (2), CF3C6F4OC6F4 (3), and C6F5 (4)) are synthesized by the facile reaction of Na2Te with bromo-fluorobenzenes, RBr. The corresponding bis(fluorophenyl)tellurium(IV) dihalides, R2TeHal2 (Hal = F, Cl, and Br) (5-16), are obtained by the oxidation of 1-4 with mild halogenating agents (XeF2, SO2Cl2, and Br2). The dihalides show temperature-dependent NMR spectra. On the basis of the 19F NMR spectra of the two series, (C6F2H3)2TeHal2 (Hal = F (5), Cl (9), and Br (13)) and R2TeCl2 (R = C6F2H3 (9), CF3C6F4 (10), CF3C6F4OC6F4 (11), and C6F5 (12)), the coalescence temperatures, T(c), and free enthalpies, DeltaG, of rotation of the TeC bonds are determined. The activation enthalpies for the dichlorides/dibromide 9-13 are in the range of 14.4-15.2 kcal mol(-1) and that for the difluoride 5 is considerably lower at 10.7 kcal mol(-1). In addition to thorough spectroscopic characterization of 1-16, the crystal structures of the monotellurides 2 and 4 as well as of the tellurium(IV) dihalides 5, 6, 9, 10, and 13 were determined. The dihalides show interesting intermolecular Te...Hal contacts, significantly shorter than the sum of the van der Waals radii, leading to different networks of association.

Journal Article↗
PubMed2001

Self-assembled organometallic [12]metallacrown-3 complexes.

The reaction of [(arene)RuCl2]2 (arene = C6H6, cymene, C6H3Et3, or C6Me6) or [Cp*RhCl2]2 with 3-hydroxy-2-pyridone in the presence of Cs2CO3 gives trinuclear metallamacrocyclic complexes. The self-assembly process was shown to be completely diastereoselective, and a racemic mixture of complexes with M(R)M(R)M(R) or MsMsMs (M=Ru, Rh) configuration was obtained. Plausible mononuclear intermediates of the formula [(arene)RuCl(C5H4NO2)] (arene = cymene, C6Me6) have been isolated and characterized. A structurally related trimer was synthesized by using [(cymene)RuCl2]2 and 3-acetamido-2-pyridone instead of 3-hydroxy-2-pyridone. The macrocycles were shown to be highly potent ionophores for Na+ and/or Li+ with negligible affinities for the larger cation K+. The selectivities of the receptors depend on the pi-ligand present: whereas the (C6H6)Ru- and (cymene)Ru complexes bind both Li+ and Na+, the (C6Me6)Ru-, (C6H3Et3)Ru-, and Cp*Rh complexes bind exclusively Li+. For all receptors, the presence of alkali metal ions can be detected electrochemically: the peak potential is shifted by > 300 mV toward anionic potential upon binding. This behavior was utilized to detect Li+ and Na+ colorimetrically. Single crystal X-ray analyses have been carried out on eight complexes, four of which are bound to an alkali metal halide ion pair. Structural parameters, which affect the affinity and selectivity are discussed. A computational study on [[MX][12]crown-3] complexes (M =Li, Na; X=Cl, Br, I) was performed in order to compare relevant bond lengths and angles of the energy-minimized structures with those of the organometallic receptors.

Journal Article↗
PubMed2001

Highly energetic tetraazidoborate anion and boron triazide adducts.

The first crystal structures of the highly energetic tetraazidoborate anion and boron triazide adducts with quinoline and pyrazine as well as of tetramethylpiperidinium azide have been determined. Synthesis procedures and thorough characterization by spectroscopic methods of these hazardous materials are given. Quantum chemical calculations were carried out for B(N(3))(4)(-), B(N(3))(3), C(5)H(5)N.B(N(3))(3), (N(3))(3)B.NC(4)H(4)N.B(N(3))(3), and the hypothetical C(3)H(3)N(3).[B(N(3))(3)](3) at HF, MP2, and B3-LYP levels of theory. The structure of tetraazidoborate was optimized to S(4) symmetry and confirmed the results obtained from the X-ray diffraction analysis. The dissociation enthalpies for the pyridine (model for quinoline) as well as for the pyrazine adduct were calculated. For pyridine-boron triazide a value of 10.0 kcal mol(-1) (for pyrazine-bis(boron triazide) an average of 2.35 kcal mol(-1) per BN unit) was obtained.

Journal Article↗
PubMed2001

Loss of cyclin A and G1-cell cycle arrest are a prerequisite of ceramide-induced toxicity in human arterial endothelial cells.

BACKGROUND: Ceramide is an important messenger of TNF- and lipid-induced apoptosis. We previously demonstrated the adverse effect of TNF in the process of reendothelialization as well as the dependence of its effect on cell-cycle regulation. The current study was designed to investigate the linkage between ceramide induced toxicity and growth arrest in human endothelial cells. METHODS AND RESULTS: Cultured human arterial endothelial cells (HAEC) served as an in-vitro model to test the cellular effects of C2-ceramide (C2). C2-induced cell death in HAECs occurred time- and dose-dependently. The LD(50) in subconfluent cells was three times lower than in confluent cell layers (25 vs. 75 microM). C2 caused up to 70% inhibition of BrdU and [3H]thymidine incorporation at non-toxic concentrations as a result of G1 cell-cycle arrest. Downregulation of cyclin A and p21(Cip1/Waf1) protein expression was observed independently of C2-toxicity, while expression of other cell-cycle regulatory genes was not affected. Inhibition of cyclin A protein expression by sequence-specific antisense-oligonucleotides was paralleled by significant growth-inhibition. The protein phosphatase inhibitor okadaic acid induced endothelial cell proliferation, which was completely abrogated by C2. In contrast, aphidicolin-synchronized endothelial cells demonstrated elevated cyclin A levels along with 30% higher BrdU-incorporation and 70% less C2-toxicity. G1-arrested cells, however, showed significantly enhanced C2-toxicity, lack of cyclin A expression and induction of uncleaved caspase-3 (CPP32). CONCLUSIONS: Ceramide abrogates endothelial cell proliferation independently of apoptosis or necrosis at low concentrations (<or=10 microM) through loss of cyclin A expression with subsequent G1 cell-cycle arrest. Synchronization of HAECs in S-phase with aphidicolin overcomes C2-induced G1-arrest and partially blocks ceramide toxicity. These findings demonstrate the dependence of ceramide toxicity on cell cycle regulation, suggesting a strong bidirectional relationship between cell-cycle control and cell death in vessel biology.

Apoptosis↗
PubMed2001

Pharmacokinetics of pantoprazole in patients with moderate and severe hepatic dysfunction.

BACKGROUND: Patients with impaired hepatic function usually require gastric acid-suppressant therapy but are at increased risk for drug interactions and may require dosage adjustments. The proton pump inhibitor pantoprazole is rapidly absorbed and eliminated, primarily by cytochrome P450 (CYP) 2C19 isozymes. OBJECTIVE: This study sought to determine whether dosage adjustment of pantoprazole is required in patients with moderate or severe hepatic impairment by comparing the pharmacokinetic profile of pantoprazole in such patients with that in healthy slow metabolizers of pantoprazole, in whom no dosage adjustment is required. METHODS: Patients with moderate (Child-Pugh class B) and severe (Child-Pugh class C) hepatic impairment received oral pantoprazole 40 mg once daily on days 1 through 4 and then on alternate days (days 6 and 8). Serial blood samples were collected on days 4 and 8 for analyses of plasma pantoprazole concentrations. Pharmacokinetic data were compared between the 2 groups with hepatic impairment and against historical data from 17 healthy subjects who were genetically slow CYP2C19 metabolizers of pantoprazole. RESULTS: Twenty-two patients participated in the study, 13 in the Child-Pugh class B group and 9 in the Child-Pugh class C group. No clinically significant differences in pantoprazole pharmacokinetics were noted between the patients with hepatic impairment and the healthy slow metabolizers of pantoprazole on days 4 and 8. Pantoprazole was well tolerated. Four Child-Pugh class B patients and 3 Child-Pugh class C patients reported > or = 1 adverse event. Adverse events were generally mild or moderate, and were similar to those reported in healthy subjects. Two patients discontinued the study because of severe events related to their underlying disease. CONCLUSIONS: The pharmacokinetics and tolerability of pantoprazole were similar in patients with moderate hepatic impairment, patients with severe hepatic impairment, and healthy slow metabolizers of pantoprazole, in whom no dosage adjustment is required. Thus, no dosage adjustment of pantoprazole is required in patients with hepatic impairment, regardless of its severity. However, caution should be exercised when giving pantoprazole to patients with severe hepatic impairment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Allelic and somatic variations in the endogenous opioid system of humans.

People with a genetic predisposition for substance abuse have defects in genes for the opioid peptides and receptors. A high number of polymorphisms have been detected in the mu-opioid receptor, some of which result in pharmacological alterations. The opioid peptide proopiomelanocortin proved extraordinarily rich in mutations that often lead to severe phenotypical consequences. Prodynorphin displays a polymorphic regulation of transcription. Variants of the mu- and the delta-opioid receptor showed positive associations with opiate and/or alcohol addiction in some studies. However, these associations were weak, indicating a small contribution of the opioid system to these disorders.

Alleles↗
PubMed2001

Alcohol enhances oxysterol-induced apoptosis in human endothelial cells by a calcium-dependent mechanism.

Controversy exists about the net effect of alcohol on atherogenesis. A protective effect is assumed, especially from the tannins and phenolic compounds in red wine, owing to their inhibition of low density lipoprotein (LDL) oxidation. However, increased atherogenesis occurs in subjects with moderate to heavy drinking habits. The purpose of this study was to investigate the influence of alcohol in combination with oxysterols on the endothelium. Cultured human arterial endothelial cells (HAECs) served as an in vitro model to test the cellular effects of various oxysterols. Oxysterols (7beta-hydroxycholesterol, 7-ketocholesterol, and cholesterol-5,6-epoxides), which are assumed to be the most toxic constituents of oxidized LDL, induced apoptosis in HAECs through calcium mobilization followed by activation of caspase-3. Ethanol, methanol, isopropanol, tert-butanol, and red wine all potentiated oxysterol-induced cell death up to 5-fold, paralleled by further induction of caspase-3. The alcohol effect occurred in a dose-dependent manner and reached a plateau at 0.05% concentration. Alcohol itself did not affect endothelial cell viability, nor did other solvents such as dimethyl sulfoxide mimic the alcohol effect. So far as the physiologically occurring oxysterols are concerned, this effect was apparent only for oxysterols oxidized at the steran ring. The possibility of alcohol facilitating the uptake of oxysterols into the cell was not supported by the data from an uptake study with radiolabeled compounds. Finally, alcohol in combination with oxysterols did cause a dramatic increase in cytosolic calcium influx. Blockage of calcium influx by the calcium channel blocker aurintricarboxylic acid or the calcium chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid abrogated the alcohol-mediated enhancement of oxysterol toxicity. We describe for the first time a mechanistic concept explaining possible adverse effects of alcohol in conjunction with physiologically occurring oxysterols on atherogenesis.

Alcohols↗
PubMed2001

Oral lichen planus: patient profile, disease progression and treatment responses.

BACKGROUND: Oral lichen planus, or OLP, is a common mucocutaneous immunological disease. The objective of this study was to describe the patient profile, disease progression and treatment responses. METHODS: The authors conducted a retrospective, descriptive study using information from patient records at a tertiary referral center. The study included 229 patients with OLP who were seen in the oral medicine clinic at the University of California, San Francisco, between September 1996 and August 2000, for the first time or for a follow-up visit. Signs and symptoms at various clinic visits were quantified. Responses to treatment and disease progression were determined by comparing scores with baseline scores. RESULTS: The mean age at onset of the disease was 55 years, and 154 (67 percent) of the patients were female. Symptoms generally correlated directly with the severity of OLP forms, which ranged from reticular to erosive. Corticosteroids were effective in reducing symptoms, healing ulcers and reducing erythema. At last follow-up, 65 percent of the patients had the same type of OLP seen initially or the disease had progressed to a more severe type, while 35 percent of patients had less-severe forms than that seen at the initial visit. Four patients (1.7 percent) developed oral squamous-cell carcinoma during the follow-up period. CONCLUSIONS: OLP is a chronic disease with no known cure. Symptoms can improve with corticosteroids; however, the lack of long-term (that is, lifetime) treatment compliance and the adverse side effects of the drugs limit optimal results. CLINICAL IMPLICATIONS: Patients with OLP should be treated if symptoms are significant. Follow-up--including supervision of medication use and monitoring of side effects, as well as periodic examinations for possible malignant transformation--is necessary.

Administration, Topical↗
PubMed2000

Polyhedral members of the Mg2nP2m family derived from dimeric magnesium trialkylsilylphosphandiide.

The magnesiation of tri(tert-butyl)silylphosphane in THF yields tetrameric (tetrahydrofuran-O)magnesium tri(tert-butyl)silylphosphandiide 1. The central moiety is a slightly distorted Mg4P4 cube with tetracoordinate magnesium and phosphorus atoms. The reaction of dibutylmagnesium with H2PSitBu3 in toluene gives tetramagnesium tetrakis[mu-tri(tert-butyl)silylphosphanide] bis[mu 4-tri(tert-butyl)silylphosphandiide] 2. The central fragment is a Mg4P2 octahedron with the phosphorus atoms in a trans position. The Mg...Mg edges are bridged by the phosphanide substituents. Crystallographic data of 1: C68H148Mg4O5P4Si4, monoclinic, P2(1)/c, a = 13.454(1) A, b = 26.123(1) A, c = 24.539(2) A, beta = 96.53(1) degrees, Z = 4; crystallographic data of 2: C72H166Mg4P6Si6, monoclinic, P2(1)/n, a = 13.951(1) A, b = 14.269(1) A, c = 24.209(2) A, beta = 102.415(1) degrees, Z = 2.

Journal Article↗
PubMed2000

Solid phase DNA amplification: characterisation of primer attachment and amplification mechanisms.

Different chemical methods used to attach oligonucleotides by their 5'-end on a glass surface were tested in the framework of solid phase PCR where surface-bound instead of freely-diffusing primers are used to amplify DNA. Each method was first evaluated for its capacity to provide a high surface coverage of oligonucleotides essentially attached via a 5'-specific linkage that satisfyingly withstands PCR conditions and leaves the 3'-ends available for DNA polymerase activity. The best results were obtained with 5'-thiol-modified oligonucleotides attached to amino-silanised glass slides using a heterobifunctional cross-linker reagent. It was then demonstrated that the primers bound to the glass surface using the optimal chemistry can be involved in attaching and amplifying DNA molecules present in the reaction mix in the absence of freely-diffusing primers. Two distinct amplification processes called interfacial and surface amplification have been observed and characterised. The newly synthesised DNA can be detected and quantified by radioactive and fluorescent hybridisation assays. These new surface amplification processes are seen as an interesting approach for attachment of DNA molecules by their 5'-end on a solid support and can be used as an alternative route for producing DNA chips for genomic studies.

Cross-Linking Reagents↗
PubMed2000

New substituted 1-(2,3-dihydrobenzo[1, 4]dioxin-2-ylmethyl)piperidin-4-yl derivatives with alpha(2)-adrenoceptor antagonist activity.

The emergence of a novel theory concerning the role of noradrenaline in the progression and the treatment of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases has provided a new impetus toward the discovery of novel compounds acting at alpha(2)-adrenoceptors. A series of substituted 1-(2, 3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-4-yl derivatives bearing an amide, urea, or imidazolidinone moiety was studied. Some members of this series of compounds proved to be potent alpha(2)-adrenoceptor antagonists with good selectivity versus alpha(1)-adrenergic and D(2)-dopamine receptors. Particular emphasis is given to compound 33g which displays potent alpha(2)-adrenoceptor binding affinity in vitro and central effects in vivo following oral administration.

Adrenergic alpha-Agonists↗
PubMed2000

A delta opioid receptor lacking the third cytoplasmic loop is generated by atypical mRNA processing in human malignomas.

delta Opioid receptors were identified in human melanomas by RT-PCR and radioligand binding. In all tumors an additional PCR amplificate was detected in which 144 bp within the third exon were deleted. This fragment corresponded to the third cytoplasmic domain of the receptor protein. The short variant resulted from atypical mRNA processing. There were no common splice recognition sequences around the deleted fragment; instead its excision resembled the removal of a transposon. The deletion was not detected in normal human melanocytes nor in human or rat brain. However, it was present in a human neuroblastoma cell line (SH-SY5Y). Thus, it appears that the occurrence of the short delta opioid receptor is correlated to malignancy.

Animals↗
PubMed2000

Nonequilibrium solid-phase microextraction for determination of the freely dissolved concentration of hydrophobic organic compounds: matrix effects and limitations.

Solid-phase microextraction (SPME) has recently been applied to measure the freely dissolved concentration, as opposed to the total concentration, of hydrophobic substances in aqueous solutions. This requires that only the freely dissolved analytes contribute to the concentration in the SPME fiber coating. However, for nonequilibrium SPME the sorbed analytes that diffuse into the unstirred water layer (UWL) adjacent to the SPME fiber can desorb from the matrix and contribute to the flux into the fiber. These processes were described as a model. Experimentally, an equilibrated and disconnected headspace was used as a reference for the freely dissolved concentration. The expected contribution of desorbed analytes to the uptake flux was measured for PCB no. 52 in a protein-rich solution, while it was not measured in a matrix containing artificial soil. The latter was possibly due to slow desorption of the analyte from the artificial soil. On the basis of the present study, a contribution of desorbed analytes to the uptake flux is expected only if(1) the rate-limiting step of the uptake process is diffusion through the UWL, (2) the concentration of the sorbed analyte is high, and (3) desorption from the matrix is fast.

Chemical Phenomena↗
PubMed2000

In vitro IgE but not IgG production of canine peripheral blood B cells is inhibited by CD40 ligation.

The aim of this study was to investigate in vitro IgE induction in peripheral canine B cells. CD21(+) B cells were purified from the peripheral blood of beagle dogs by positive selection via magnetic separation to a purity of >/=95%. Subsequently, proliferation, and IgG and IgE production of canine B cells were investigated after stimulation with human recombinant Interleukin-4 (hrIL-4) and human recombinant Interleukin-2 (hrIL-2) in the presence or absence of CD40L-CD8 fusion protein (CD40L) of mouse origin. We could demonstrate that canine B cells react on hrIL-2 alone by proliferation and IgG production but not by IgE secretion, whereas activation with hrIL-4 induced proliferation and mainly IgE production. Together, both cytokines synergistically increased B cell proliferation as well as IgG and IgE production. We could also show that mouse CD40L induces proliferation of dog B cells, which is further enhanced by addition of hrIL-4. Unexpectedly, CD40L led to a dramatic decrease in the IL-4 mediated IgE secretion (82% inhibition on an average). In contrast, IgG production was not affected significantly by CD40L. The same effects of CD40L were observed when B cells were stimulated by a combination of IL-2 and IL-4 and this inhibition could not be abrogated by increasing the amounts of IL-4. In summary, activation of canine B cells from peripheral blood by hrIL-4 in the presence or absence of hrIL-2 led to marked IgE production that is strongly and in a dose-dependent manner inhibited by CD40L. Stimulation of IgG production is not influenced by CD40L.

Animals↗
PubMed2000

Tuning of vertical and lateral correlations in self-organized PbSe/Pb1-xEuxTe quantum dot superlattices

The tuning of lateral and vertical correlations in self-organized PbSe/Pb 1-xEu xTe quantum dot superlattices by changes in the spacer thicknesses is demonstrated and shown to be due to finite size effects in the dot-dot interactions. As a consequence, different dot arrangements such as vertically aligned dot columns or fcc stacking are obtained for a single material system without changes in growth conditions. The different dot superstructures are shown to exhibit a different scaling behavior of the lateral versus vertical dot separation, as well as a different evolution of dot sizes and shapes.

Journal Article↗