Search PubMed⌕ Search

Biomedical subjects

H Brunner

Publications and source records attributed to H Brunner.

At least 91 records · Page 5Linked to original sources
PubMed1993

Long-term benefit of 1-year amiodarone treatment for persistent complex ventricular arrhythmias after myocardial infarction.

BACKGROUND: In the Basel Antiarrhythmic Study of Infarct Survival trial, low-dose amiodarone improved 1-year survival in patients with asymptomatic complex ventricular arrhythmias persisting 2 weeks after myocardial infarction. To assess whether this beneficial effect persisted despite discontinuation of amiodarone after 1 year, the long-term outcomes of all patients of the amiodarone-treated group (initially n = 98) and those of the control group (n = 114) were assessed. METHODS AND RESULTS: After a mean follow-up of 72 (55-125) months, information on 96% of patients (203 of 212) was obtained regarding survival or cause of death. The probability of death after 84 months according to actuarial life-table analysis (Kaplan-Meier) was 30% for the amiodarone-treated patients and 45% for control patients. For the total follow-up, mortality remained significantly lower in the amiodarone group versus the control group regarding all deaths (p = 0.03) as well as cardiac death (p = 0.047). This mortality reduction was entirely due to the first-year amiodarone effect, since there was no significant mortality difference between groups when considering survival after discontinuation of amiodarone only. CONCLUSIONS: These data suggest that the beneficial effect of amiodarone on survival in this high-risk group of patients persists for several years. In addition, the results stress the importance of early treatment after myocardial infarction, whereas the rate of sudden death and all cardiac death is low (1.6% and 4.1% per year, respectively) during late follow-up and therefore may not warrant further therapy.

Amiodarone↗
PubMed1993

Expression of major histocompatibility complex class II antigens and levels of interferon-gamma, tumour necrosis factor, and interleukin-6 in cerebrospinal fluid and serum in Toxoplasma gondii-infected SCID and immunocompetent C.B-17 mice.

In order to investigate activation of the innate immune system in murine toxoplasmosis, T- and B-cell-deficient SCID mice and their co-isogenic immunocompetent C.B-17 counterparts were orally infected with a low-virulent strain of Toxoplasma gondii (DX strain). SCID mice developed a fatal necrotizing toxoplasmosis, whereas CD4+ and CD8+ T cells contributing to inflammatory infiltrates conferred resistance to immunocompetent mice. Significant amounts of interferon-gamma (IFN-gamma) were detectable in SCID mice. The most likely source for this cytokine is activated natural killer (NK) cells. In comparison to immunocompetent mice IFN-gamma levels were reduced in cerebrospinal fluid (CSF) and serum of SCID mice at days 7 and 14 of disease. Similar amounts of tumour necrosis factor (TNF) were detected in both strains of mice. In addition, immunohistochemistry showed major histocompatibility complex (MHC) class II antigen expression on SCID and C.B-17 microglial cells and macrophages demonstrating activation of these cells in both strains. However, the up-regulation of MHC class II antigen on microglia was less pronounced in SCID mice, presumably due to reduced levels of IFN-gamma. Interleukin-6 (IL-6) levels in CSF and serum were elevated in both strains and correlated with systemic and intracerebral disease activity. In conclusion, our results demonstrate activation of macrophages and NK cells as the predominant defence mechanisms of the comprised SCID immune system during toxoplasma infection. This implies a major role for the innate immune system during early stages of toxoplasmosis although T cells are necessary to control the infection efficiently.

Animals↗
PubMed1992

Directed enzymatic synthesis of linear and branched gluco-oligosaccharides, using cyclodextrin-glucanosyltransferase.

Cyclodextrin-glucanosyltransferase, in a kinetically controlled reaction, transfers one maltohexaosyl residue from cyclomaltohexaose (alpha CD) to HO-4 of an acceptor to form a linear or a branched gluco-oligosaccharide. The primary transfer product can be isolated in yields up to 45% and in high purity, if the reaction is stopped at an early stage. With increasing time of incubation, secondary and tertiary transfer products are formed by stepwise addition of maltohexaosyl units. At equilibrium, a mixture with almost equal proportions of oligosaccharides is obtained. Glucose and malto-oligosaccharides of any chain length carrying a free 4-hydroxyl group and with HO-1 free or substituted, and regardless of the configuration at C-1, may serve as acceptors. Substrates with galacto or manno configuration were not utilised by the enzyme. The selectivity of the enzyme with respect to the site of chain elongation in branched acceptor molecules has been investigated. The technique described here may be applied to prepare linear gluco-oligosaccharides of any chain length of branched oligosaccharides of the amylopectin type.

Bacillus↗
PubMed1992

Production and characterization of four anti-neuropeptide Y monoclonal antibodies.

Human neuropeptide Y (hNPY) is a potent vasoconstrictor peptide of 36 aminoacid residues. We isolated hybridomas secreting four monoclonal antibodies directed against various epitopes of neuropeptide Y and studied their cross-reactivity with peptide YY (PYY) and the pancreatic polypeptide (PP), two peptides sharing sequence homologies with hNPY (respectively 70% and 50%). The antibody NPY02 is an IgG1 with a Ka of 5.5 x 10(10) liters/mol. It binds to the 11-24 region of NPY (IC50 = 2 x 10(-7)M), does not recognize PP but cross-reacts weakly with PYY. Antibodies NPY03 and NPY05 are IgG2 with respective Ka's of 6.7 x 10(9) and 2.5 x 10(10) liters/mol. They interact with a C-terminal epitope on NPY (NPY 27-34, IC50 = 2 x 10(-9) M for NPY03 and NPY 32-36, IC50 = 1 x 10(-9) M for NPY05). These two antibodies cross-react with PYY whereas only NPY05 binds PP. NPY05 is unable to bind the free acid form of neuropeptide Y. The 32-36 COOH free subpeptide is recognized 50,000 less efficiently by NPY05 than its amidated form. Antibody NPY04 is an IgG3 with a Ka of 3.8 x 10(8) liters/mol. It recognizes a N-terminal epitope between aminoacids 1 and 12 (IC50 = 2.5 x 10(-6) M). NPY04 interacts weakly with PYY but not detectably with PP. These results obtained with 4 different monoclonal antibodies demonstrate the presence of at least four epitopes on hNPY, two of them being continuous. These antibodies will be used to study the interaction of NPY with its receptor and to develop sensitive and specific assays for determination of NPY concentrations in biological fluids.

Amino Acid Sequence↗
PubMed1992

K-dependent inhibition in the dentate-CA3 network of guinea pig hippocampal slices.

1. The occurrence of potassium-dependent inhibitory postsynaptic potentials (K-IPSPs) in relation to burst discharges induced by 4-aminopyridine (4-AP; 30 microM) was studied in CA3, granule and hilar neurons in guinea pig hippocampal slices with the use of paired extra- and/or intracellular recording. 2. Slow small (2-5 mV) and large (up to 30 mV) K-IPSPs were observed in CA3, granule and in some hilar neurons during 4-AP applications in the presence of blockers for fast synaptic transmission, picrotoxin (50 microM), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5-10 microM). Amplitudes of K-IPSPs were linearly related to voltage, and they reversed in sign close to -100 mV, as expected for synaptic potentials generated by an increase in K-conductance. 3. In CA3 neurons, 4-AP applied in the presence of picrotoxin elicited burst discharges and K-IPSPs. CNQX blocked the burst discharge activity and increased the amplitude of K-IPSPs. 4. In granule cells, 4-AP applied in the presence of picrotoxin elicited K-IPSPs and only inconsistently small excitatory postsynaptic potentials (EPSPs). The EPSPs were blocked by CNQX, but CNQX application did not affect the K-IPSPs. However, in granule cells it could be observed that blockade of Cl-inhibition by picrotoxin in the presence of CNQX increased the amplitude of K-IPSPs. 5. In hilar neurons, 4-AP applied in the presence of picrotoxin elicited mainly burst discharges. CNQX blocked the burst discharges only in a few cells. In most hilar neurons K-IPSPs were observed at the beginning of the 4-AP effect, but subsequently K-IPSPs were replaced by burst discharges. 6. To determine the type of cells that burst in picrotoxin and 4-AP, neurons were stained intracellularly with horseradish peroxidase. Neurons stained in the granule cell layer did not burst and were morphologically identified as granule cells. Neurons stained in the hilar region burst and were nonpyramidal, nongranule cells. Bursting cells stained in the CA3 area were all pyramidal cells. 7. The hilar neurons varied considerably in size and dendritic organization. They could be classified as aspiny and spiny cells, the latter including mossy cells. 8. We conclude that K-dependent inhibition may explain the long-lasting IPSPs observed in in vivo recordings from hippocampal cells. In a hippocampal lamella, burst discharge activity of hilar neurons including presumed excitatory mossy cells is associated with inhibition of granule cells.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMed1992

Granule cell inhibition and the activity of hilar neurons.

Electrophysiological data from guinea pig hippocampal slices together with available morphological information about the dentate granule cell--hilar neuron circuitry strongly suggest that hilar neurons largely contribute to postsynaptic inhibition of granule cells. As in hippocampal pyramidal cells, inhibitory postsynaptic potentials in granule cells are either due to an increase in Cl-conductance or to an increase in K-conductance. It is therefore further suggested that hilar neurons inhibiting granule cells belong to at least two functionally distinct groups, those generating Cl-dependent and those generating K-dependent IPSPs. The presumed inhibitory action of hilar neurons is underlined by experiments applying pharmacological tools to suppress or enhance hilar neuron activity. Hyperpolarization of hilar neurons by the presumed GABAB-agonist (-)baclofen is associated with disinhibition of granule cells. If hilar neurons are activated by 4-amino-pyridine or picrotoxin to discharge in repetitive bursts, granule cells display repetitively occurring inhibitory postsynaptic potentials.

4-Aminopyridine↗
PubMed1992

[Time of famotidine administration and healing of duodenal ulcer: is 18.00 o'clock of importance?].

In a double-blind, placebo-controlled two centre trial, the effect of a 40 mg oral dose of famotidine administered at 6 p.m. to the same dose given at 10:00 p.m. was studied in 38 patients with duodenal ulcers. After 2 weeks 61% of the ulcers had healed; this had risen to 89% by the end of week 4. The statistically non-significant trend to better results following administration later at night (which apparently contradicts other published results) may have been due to a delay in adsorption caused by food ingestion and the related nocturnal pH levels.

Dose-Response Relationship, Drug↗
PubMed1991

Pallister-Killian syndrome: characterization of the isochromosome 12p by fluorescent in situ hybridization.

The isochromosome 12p (i(12p)) in fibroblasts of 3 patients with Pallister-Killian syndrome and one decreased prematurely born neonate, was characterized by fluorescent in situ hybridization (FISH) using chromosome 12-specific DNA probes. FISH is a useful technique for rapid and reliable detection and characterization of the i(12p) chromosome in Pallister-Killian patients. Detection was possible also in interphase cells. In addition, the in vitro selection against i(12p) cells at different passages in fibroblast cultures of two patients was monitored.

Abnormalities, Multiple↗
PubMed1991

A model for the role of HLA-DQ molecules in the pathogenesis of juvenile chronic arthritis.

Restriction fragment length polymorphism (RFLP) typing of MHC-class II loci DRB, DQA1, DQB1, DQA2 and DPB1 was performed in 94 patients with seronegative juvenile chronic arthritis (JCA) and 184 random controls. Analysis of allele frequencies and MHC-class II 4-loci haplotypes indicate: (1) Susceptibility to JCA is more strongly associated with the HLA-DQ subregion than with the HLA-DR subregion, especially in early onset pauciarticular JCA (EOPA-JCA). (2) Haplotype and sequence analysis show two independent MHC-class II associations for susceptibility to EOPA-JCA, one located in DQA1, the other in DPB1. (3) Two RFLP defined patterns of the DQA1 locus, DQA1.5 (DQA1*0501) and DQA1.8 (DQA1*0401, *0601) are strongly associated with the disease. (4) Analysis of amino-acid (AA) sequences coded in exon 2 of DQA1 reveals an AA sequence of six AAs common to all three associated DQA1 alleles. This suggests a model that includes a functional role for HLA-DQ molecules in the pathogenesis of JCA.

Alleles↗
PubMed1991

Physical and genetic mapping of a novel chromosome 19 ERCC1 marker showing close linkage with myotonic dystrophy.

Recent genetic linkage analyses have mapped the myotonic dystrophy locus to the region of 19q13.2-13.3 lying distal to the gene for creatine kinase subunit M (CKM). The human excision repair gene ERCC1 has also been mapped to this region of chromosome 19. A novel polymorphic DNA marker, pEO.8, has been isolated from a chromosome 19 ERCC1-containing cosmid that maps to a 300-kb NotI fragment encompassing both CKM and ERCC1. Genetic linkage analysis reveals close linkage between pEO.8 and myotonic dystrophy (DM) (zmax = 19.3, theta max = 0.01). Analysis of two key recombinant events suggests a mapping of DM distal to pEO.8 and CKM.

Blotting, Southern↗
PubMed1991

[Uni- and bilateral lung transplantation: patient evaluation and selection. Vienna Lung Transplant Group].

Lung transplantation has been available as a therapeutic option for patients with end-stage lung disease for only a short period of time. Since this procedure is now being successfully performed with increasing frequency in various transplantation centers, we must now begin to consider transplantation as a therapeutic options in patients with lung diseases unresponsive to medical therapy. Physicians are required to know principles involved for determination of suitable candidates and operative procedures of choice. We report here our experiences of preoperative assessment of patients undergoing lung transplantation. Patient selection, indications, contraindications, choice of operation, appropriate timing for transplantation and preoperative rehabilitation methods are discussed. It is concluded that appropriate recipient selection remains an important determinant for the success of this treatment modality.

Austria↗
PubMed1991

[Antitumor platinum(II) complexes with substituted 2-aminomethylpyridine ligands].

Reaction of K2PtCl4 with the substituted 2-aminomethylpyridines 9, 14, and 22 affords the corresponding dichloroplatinum(II) complexes 3-5. Compounds 3 and 22 show remarkable relative binding affinities for the estrogen receptor. Towards the hormone-independent P388-tumor of the CD2F1-mouse the platinum(II) complexes 4 and 5 are weakly active, complex 3 is inactive. Towards the hormone-independent MDA-MB 231-cell line, compounds 3-5, 9, 14, and 22 exhibit no significant antitumor activity. Towards the hormone-dependent MCF-7 cell line, compounds 3-5, 9, 14 show weak antitumor activity, whereas compound 22 exhibits strong inhibition.

Animals↗
PubMed1990

Midline facial defects with ocular colobomata.

We describe 5 children with midline facial anomalies and iris colobomata reminiscent of frontonasal "dysplasia." Two patients have, in addition, abnormalities of the eyelids and one of them probably has the rare autosomal recessive condition frontofacionasal "dysplasia." The patients may have a new syndrome of midline facial defects, iris colobomata, and mental retardation.

Abnormalities, Multiple↗