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H J Müller

Publications and source records attributed to H J Müller.

At least 73 records · Page 4Linked to original sources
PubMed1995

Visual search for singleton feature targets within and across feature dimensions.

Three experiments investigated visual search for singleton feature targets. The critical dimension on which the target differed from the nontargets was either known in advance or unknown--that is, the critical difference varied either within a dimension or across dimensions. Previous work (Treisman, 1988) had shown that, while the search reaction time (RT) functions were flat in both conditions, there was an intercept cost for the cross-dimension condition. Experiment 1 examined whether this cost would disappear when responses could be based on the detection of any (target-nontarget) difference in the display (by requiring a "heterogeneity/homogeneity" decision). The cost remained. This argues that pop-out requires (or involves) knowledge of the particular dimension in which an odd-one-out target differs from the nontargets; furthermore, that knowledge is acquired through the elimination of dimensions not containing a target. In Experiment 2, the subjects had to eliminate (or ignore) one potential source of difference in order to give a positive response (displays could contain a "noncritical" difference requiring a negative response). The result was a comparatively large cost in the within-dimension (positive) condition. This can be taken to indicate that pop-out as such does not make available information as to the particular feature value in which the target differs from the nontargets. Experiment 3 examined whether search priorities can be biased in accordance with advance knowledge of the likely source of difference. The subjects were found to have a high degree of top-down control over what particular dimension to assign priority of checking to. The implication of the results for models of visual search and selection are discussed.

Adult↗
PubMed1995

Kringle 4 of human apolipoprotein[a] shares a linear antigenic site with human catalase.

Monoclonal antibody (mab) 1A2, directed against human apolipoprotein[a] (apo[a]), revealed a strong reaction with peroxisomes as shown by immuno-gold labeled cryosections of human liver biopsies. This reactivity was not due to the presence of apo[a] in peroxisomes but to a cross-reactivity of mab 1A2. Immunoblot analysis of peroxisomal fractions and purified human catalase demonstrated that mab 1A2 reacts with catalase. Conversely, an anti-catalase antibody also recognized apo[a]. By sequence comparison we identified a 4-amino acid motif (Y-Y-P-N) that is shared between the highly repetitive kringle 4 motif of apo[a] and the carboxy-terminal third of the peroxisomal marker enzyme catalase. No other identical sequences were identified in these proteins. Results from the following experiments indicated that 1A2 recognizes this short linear epitope. i) Mab 1A2 reacted only with the 4 amino acid peptide sequence in a pin-ELISA using immobilized overlapping peptides. ii) A synthetic peptide including this sequence completely inhibited the 1A2 immunoreactivity to apo[a] and catalase. iii) A recombinant fusion protein tagged with the putative epitope was recognized by mab 1A2. Our findings demonstrate that unknown linear epitopes in native proteins can be identified by sequence comparison between known proteins. The practical implication is that antibodies against apo[a] must be controlled for this cross-reactivity before using them for immunohistochemical studies of intracellular apo[a] in tissues or cells.

Amino Acid Sequence↗
PubMed1995

Ten allelic apolipoprotein[a] 5' flanking fragments exhibit comparable promoter activities in HepG2 cells.

Plasma levels of the atherogenic lipoprotein[a] represent a quantitative genetic trait that is primarily controlled by the polymorphic apolipoprotein[a] locus on chromosome 6q. The more than 1000-fold variation in lipoprotein[a] plasma levels is explained to a large extent by a remarkable size polymorphism of the apolipoprotein[a] gene which is translated into apolipoprotein[a] isoforms and by unidentified sequence variation in apo[a]. In a recent report, sequence variation in a 1.5 kb fragment from the 5' flanking region of the apolipoprotein[a] gene was associated with different promoter activities, which led to the suggestion that transcriptional control of the apolipoprotein[a] gene might contribute significantly to lipoprotein[a] plasma levels. We have used a reporter gene assay to compare the promoter activities of these 1.5 kb fragments which were cloned from ten well-characterized apolipoprotein[a] alleles. These ten allelic apolipoprotein[a] fragments revealed, despite the same sequence variation as previously reported, comparable and relatively weak promoter activities in HepG2 hepatocarcinoma cells. Promoter activity for the same fragment in non-liver cells and the identification of a liver cell-specific DNaseI hypersensitive site 3 kb upstream from the ATG start codon suggest that longer fragments must be used in order to analyze the transcriptional regulation of the apolipoprotein[a] gene.

Alleles↗
PubMed1995

[Right ventricular function in patients with obstructive sleep apnea].

Obstructive sleep apnea often affects the cardiovascular system. So far, only few data are available on its influence on the function of the right ventricle that can be evaluated by gated radionuclide ventriculography. This technique was performed on 68 patients with polysomnographically verified obstructive sleep apnea. 27.9% of the patients showed an impairment of right ventricular function. There was no correlation between right ventricular function and degree of obstructive sleep apnea or pulmonary artery pressures--as evaluated by right heart catheterization. Gated radionuclide ventriculography thus seems to be suitable for early detection of pathological effects of obstructive sleep apnea on the function of the right ventricle.

Adult↗
PubMed1994

Partial purification of a type eta protein kinase C from murine brain: separation from other protein kinase C isoenzymes and characterization.

Various murine tissues were tested, by using a protein kinase C-eta-specific antiserum, for the expression of type eta protein kinase C. Brain was found to be the richest source of a type eta isoenzyme. Native protein kinase C-eta was partially purified from the cytosol of murine brain by chromatography on DEAE-Sepharose, hydroxyapatite and protamine-agarose. This procedure resulted in a separation of protein kinase C-eta from the other phorbol 12-myristate 13-acetate (PMA)-responsive isoenzymes (alpha, beta, gamma, delta, epsilon) and allowed, for the first time, characterization of the native enzyme. The protein kinase C of type eta from mouse brain is a phospholipid-dependent Ca(2+)-unresponsive protein kinase. Both PMA and bryostatin activate the kinase for phosphorylation of a substrate as well as for autophosphorylation. Various pseudo-substrate-related peptides are suitable as substrates for the eta-type kinase, peptide delta being the best and peptides eta and epsilon the poorest substrates. The enzyme is inhibited by staurosporine and staurosporine-related compounds, such as K252a and Gö 6976. However, protein kinase C-eta, like protein kinase C-delta, is around two orders of magnitude less sensitive towards Gö 6976 than are the Ca(2+)-responsive isoenzymes (alpha, beta, gamma). The eta-type protein kinase C exhibits an extreme tendency to lose its PMA-responsiveness. Consequently, purification of the enzyme to homogeneity has not yet been successful.

Alkaloids↗
PubMed1994

Rottlerin, a novel protein kinase inhibitor.

Rottlerin, a compound from Mallotus philippinensis, is shown to inhibit protein kinases with some specificity for PKC. To some extent, the novel inhibitor is able to differentiate between PKC isoenzymes, with IC50 values for PKC delta of 3-6 microM, PKC alpha,beta,gamma of 30-42 microM and PKC epsilon,eta,zeta of 80-100 microM. Inhibition of PKC appears, at least in part, to be due to a competition between rottlerin and ATP. Among the protein kinases tested, only CaM-kinase III is suppressed by rottlerin as effectively as PKC delta. The chemical structure of rottlerin might serve as a basis for the development of novel inhibitors with improved selectivity for a distinct PKC isoenzyme, such as PKC delta, or for CaM-kinase III.

Acetophenones↗
PubMed1994

Alterations of regular and mature monocytes are distinct, and dependent of intensity and duration of exercise.

Circulating monocytes comprise functionally distinct regular (CD14bright+) and mature (CD14low+) cells. Cell surface receptors were determined by three colour flow cytometry in 8 healthy control subjects. Compared to regular monocytes, mature monocytes had lower levels of the high affinity Fc gamma receptor 1 (CD64), complement receptor 3 (CD11b), CD45RO and higher levels for HLA-DR, LFA-1 (CD11a/CD18), interleukin-2 receptor (CD25), CD45RA and the Fc gamma receptor 3 (CD16). Both regular and mature monocytes were measured before and up to three hours after four different types of exercise (Ex) in endurance trained athletes (n = 9-16). Immediately after anaerobic exercise of 1 min with a maximal lactate concentration (la max) of 12.3 (SD 1.4) mmol.1-1 and exhaustive exercise of 24 (SD 8) min with a maximal lactate concentration (lamax) of 7.4 (SD 2.6) mmol..-1 mature monocytes increased more than regular monocytes. Exhaustive endurance exercise of 87 (SD 21) min [lamax 3.7 (SD 1.0)] led to a similar increase of regular and mature monocytes. 15-33 min after a 100km run regular monocytes increased significantly, whereas mature monocytes decreased. Up to three hours after the end of all exercises mature monocytes fell below pre-exercise values. In conclusion, duration and intensity of exercise alter distinct maturation stages of monocytes differently. It is probable that the avidity of adhesion molecules like LFA-1 to their endothelial ligands is increased to enable the firm attachment to the endothelium.

Adult↗
PubMed1994

Search via recursive rejection (SERR): visual search for single and dual form-conjunction targets.

Models of visual search that assume spatially serial processing of conjunction stimuli break down when displays contain 2 identical conjunction targets: (a) They fail to account for the slopes of the target-absent reaction time (RT)/display size functions, both when the target-present response requires the detection of only 1 of the 2 targets and when it requires the detection of both targets and (b) under redundant target conditions, the probability of "fast" present RTs is greater than that expected from the independent (serial) processing of the target stimuli. This article shows that G. W. Humphreys and H.J. Müller's (1993) parallel search via recursive rejection (SERR) model can account for human search performance under dual-target conditions. In SERR, simple form conjunctions are coded and grouped (on the basis of their similarity) in a spatially parallel manner, and targets are detected through the activation of a temporary "template" or through the recursive rejection of grouped distractors.

Adult↗
PubMed1994

Perceptual integration of motion and form information: is the movement filter involved in form discrimination?

Seven experiments reinvestigated J. Driver and P. McLeod's (1992) report of a "visual search asymmetry reversal" in a task that required the integration of motion and form information. They found that, when the form discrimination was easy, search was more efficient for a moving rather than a stationary conjunction target; the reverse was true when form discrimination was difficult. J. Driver and P. McLeod proposed that 2 mechanisms are involved: a "stationary form system," which supports accurate form discrimination but is relatively insensitive to movement, and a "movement filter," which segregates the moving from the stationary items but is relatively insensitive to aspects of form. The present experiments failed to find the asymmetry reversal. The results agree with the (more parsimonious) proposal that the function of the movement filter is limited to separating moving from stationary items, whereas form discrimination is accomplished within a unitary form system.

Adolescent↗
PubMed1994

Qualitative differences in response bias from spatial cueing.

Two response bias parameters were examined in a spatial (peripheral) cueing paradigm: (i) "cued location bias": the relative probability with which a signal is incorrectly assigned to the cued location; and (ii) "likelihood ratio (beta)": the amount of evidence required to decide that a signal appeared at a particular, cued or uncued, location. The two parameters were found to be differentially sensitive to the stimulus onset asynchrony (SOA) between peripheral cue and target. Cued location bias was strongly affected by SOA, decreasing within 300 ms after peripheral cue onset. In contrast, the difference in beta between cued and uncued locations (cued < uncued) was independent of SOA. This suggests that cued location bias reflects strong but transitory pathway pre-activation following a peripheral cue, consistent with accounts of response bias effects in terms of relatively "early" processes of stimulus coding (e.g., Hawkins, Shafto, & Richardson, 1988; Shulman & Posner, 1988). In contrast, beta effects predominantly reflect "late" decision making processes that differentially weight the sensory evidence from cued and uncued locations according to their a-priori signal probabilities (e.g., Müller & Findlay, 1987; Shaw, 1982).

Adult↗
PubMed1994

Suppressed PMA-induced oxidative burst and unimpaired phagocytosis of circulating granulocytes one week after a long endurance exercise.

Ten endurance athletes performed two exhaustive intensive endurance exercises (Ex1: 21 +/- 7 min; Ex2: 18 +/- 6 min) on a cycle ergometer at 110% of their individual anaerobic threshold (maximal lactate concentration at Ex1: 9.7 +/- 2.3 mmol.1-1, Ex2: 9.5 +/- 2.2 mmol.l-1). Ex1 was performed two weeks before, Ex2 8 or 9 days after a long endurance competition (duration: 762 +/- 74 min), respectively. At both exercises before, at the 10th, during the last two and 60 minutes after exercise venous blood samples were taken to determine rat and activity of phagocytosis (FITC-conjugated, opsonized E. coli) and oxidative burst (intracellular oxidation of dihydrorhodamine123 to rhodamine123 after induction by phorbol-myristate-acetate) was measured in circulating granulocytes by flow cytometry. Statistical analysis was performed with procedures of ANOVA. Neither at Ex1 nor at Ex2 rate or activity of phagocytosis changed significantly over time, a difference between Ex1 and Ex2 was not observed. In contrast to Ex1, at Ex2 the bactericidal capacity of granulocytes decreased significantly by 37% at the end of exercise. This effect at Ex2 was reversible within the first hour of recovery. The observed transient and partial suppression of the oxydative burst was not accompanied by clinically apparent infections. Therefore, we conclude that the observed in vitro effect is without major clinical importance in healthy subjects.

Adult↗
PubMed1994

[Not Available].

Explore the source record for details and available documents.

Dentistry↗
PubMed1994

The regulatory view on drug-drug interactions.

Nowadays the majority of patients receive more than one drug simultaneously. Since drug-drug interactions and side-effects increase in a nonlinear fashion with the number of drugs administered, a drug, which might interact with a commonly used comedication should be tested specifically and systematically in this regard before marketing. So far no regulatory framework precisely defines the requirements and the design of particular drug interaction studies. The directions and guidelines of the European Community contain only general outlines about preferred study designs and the necessity of drug interaction studies. Valuable information can be found in the Guideline Special Population of the International Conference on Harmonization (ICH). On the other hand, the general character of existing regulations enables the researcher to apply the most suitable approach to uncover therapeutically relevant interactions of a new drug before marketing. After marketing approval postmarketing surveillance is necessary to detect further drug interactions of clinical relevance.

Drug Interactions↗
PubMed1994

Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3.

The human DNA excision repair gene ERCC3 specifically corrects the nucleotide excision repair (NER) defect of xeroderma pigmentosum (XP) complementation group B. In addition to its function in NER, the ERCC3 DNA helicase was recently identified as one of the components of the human BTF2/TFIIH transcription factor complex, which is required for initiation of transcription of class II genes. To date, a single patient (XP11BE) has been assigned to this XP group B (XP-B), with ther remarkable conjunction of two autosomal recessive DNA repair deficiency disorders: XP and Cockayne syndrome (CS). The intriguing involvement of the ERCC3 protein in the vital process of transcription may provide an explanation for the rarity, severity, and wide spectrum of clinical features in this complementation group. Here we report the identification of two new XP-B patients: XPCS1BA and XPCS2BA (siblings), by microneedle injection of the cloned ERCC3 repair gene as well as by cell hybridization. Molecular analysis of the ERCC3 gene in both patients revealed a single base substitution causing a missense mutation in a region that is completely conserved in yeast, Drosophila, mouse, and human ERCC3. As in patient XP11BE, the expression of only one allele (paternal) is detected. The mutation causes a virtually complete inactivation of the NER function of the protein. Despite this severe NER defect, both patients display a late onset of neurologic impairment, mild cutaneous symptoms, and a striking absence of skin tumors even at an age of > 40 years. Analysis of the frequency of hprt- mutant T-lymphocytes in blood samples suggests a relatively low in vivo mutation frequency in these patients. Factors in addition to NER deficiency may be required for the development of cutaneous tumors.

Amino Acid Sequence↗
PubMed1993

Cys4057 of apolipoprotein(a) is essential for lipoprotein(a) assembly.

Lipoprotein(a) contains one copy each of apolipoprotein B-100 and apolipoprotein(a). It has been hypothesized that a disulfide bond might exist between Cys4057 of apolipoprotein(a) and Cys3734 in apolipoprotein B-100. To investigate the role of Cys4057 for lipoprotein(a) assembly, wild-type and in vitro mutagenized apolipoprotein(a) cDNA plasmids were expressed in the human hepatocarcinoma line HepG2. The mutant plasmids encoded apolipoprotein(a) species with Cys4057 exchanged to either serine or glycine. Untransfected HepG2 cells, although able to secrete apolipoprotein B-100-containing lipoproteins, do not synthesize detectable amounts of apolipoprotein(a). After transfection of wild-type plasmid, almost all apolipoprotein(a) in the culture supernatant was present in lipoprotein(a)-like particles as demonstrated by immunoblotting, density-gradient centrifugation, and ELISA. The same analysis performed with supernatants of cells transfected with plasmids mutated in codon 4057 revealed free apolipoprotein(a) glycoprotein without detectable amounts of lipoprotein-associated apolipoprotein(a). Our results strongly suggest the existence of a disulfide bridge between Cys4057 of apolipoprotein(a) and apolipoprotein B-100 within recombinant lipoprotein(a) particles. Furthermore, they indicate that disulfide bridge formation is essential for assembly of the lipoprotein(a)-like complex produced by HepG2 cells and suggest a similar role of Cys4057 during lipoprotein(a) assembly in vivo.

Amino Acid Sequence↗
PubMed1993

[Patient without being ill? Benefit and risks of presymptomatic diagnosis].

A steadily growing number of genetic disorders or for predispositions disease can already be identified prior to their clinical manifestation. Gene technology has a considerable impetus on the development of presymptomatic or preclinical testing. Using familial cancer as a model it will be shown that persons at risk can be protected from the severe consequences of their genetic traits and can be counselled with certainty with respect to their family planning. However, such hopes are accompanied by fears that this type of genetic analysis will be performed without appropriate genetic counselling, without accepted medical practices or without the necessary quality control and that the results may be misinterpreted or misused by third parties. Informing the medical profession and the public about presymptomatic testing is the best way to prevent such negative consequences.

Ethics, Medical↗