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Biomedical subjects

H J Müller

Publications and source records attributed to H J Müller.

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

Effects of leflunomide (HWA 486) on expression of lymphocyte activation markers.

Leflunomide (HWA 486), an isoxazol derivative, has been shown to be very effective in combating autoimmune diseases and transplantation rejection in a great number of animal models. The main metabolite of leflunomide, A77 1726, is a potent antiproliferative compound. To further elucidate this effect, lymphocytes of healthy human donors were cultured for 24, 48 or 72 h in the presence of PHA or immobilized anti-CD3 antibody. A77 1726 was added at concentrations between 10 and 100 microM. Flow cytometric evaluation of early activation or proliferation markers (IL-2 and transferrin receptors, respectively) showed that their expression was inhibited in a dose-dependent manner by A77 1726. Together with previous data, these experiments indicate that leflunomide not only inhibits the expansion of already proliferating lymphocytes, but also impairs PHA and anti-CD3 antibody triggered activation of quiescent cells. Thus, this compound may exert its effects through influencing two important aspects of an immune response, that is, activation and proliferation of lymphocytes.

Adult↗
PubMed1993

Comparative pharmacokinetics and serum bactericidal activities of SCE-2787 and ceftazidime.

Ceftazidime and the new SCE-2787 are parenteral cephalosporins with a broad antimicrobial spectrum. Pharmacokinetics, serum bactericidal activities, and side effects were investigated in a randomized crossover study. A total of 12 healthy volunteers received a 20-min infusion of 1.5 g of SCE-2787 or 2.0 g of ceftazidime. Serum and urine concentrations were determined by the bioassay method and by high-pressure liquid chromatography (HPLC). The mean (+/- standard deviation) drug concentrations in serum at the end of infusion of SCE-2787 and ceftazidime were 124.4 +/- 23.8 and 233.1 +/- 54.1 mg/liter, respectively. The urine recovery of SCE-2787 was 87.8% +/- 5.5% of dose in 24 h and for ceftazidime was 85.8% +/- 6.3% of dose in 24 h. Metabolites of SCE-2787 could not be detected by HPLC in serum or urine. Pharmacokinetic parameters were calculated both with a noncompartmental analysis and on the basis of an open two-compartment model (drugs are administered into and eliminated from a central compartment only. However, reversible drug distribution from the central space occurs simultaneously into one peripheral space). The area under the concentration time curve from 0 h to infinity of SCE-2787 was 197.9 +/- 25.4 mg.h/liter, and that of ceftazidime was 334.2 +/- 40.0 mg.h/liter. SCE-2787 had a mean terminal half-life in the elimination phase of 109.0 +/- 15.3 min, while that of ceftazidime was 99.0 +/- 13.4 min. The volume of distribution at steady state of SCE-2787 was 17.1 +/- 1.6 liters/70 kg, and that of ceftazidime was 122.9 +/- 1.3 liters/70 kg. The mean residence time of SCE-2787 was 136.4 +/- 15.4 min, and that of ceftazidime was 122.9 +/- 12.7 min. The renal clearance per. 1.73 m2 of SCE-2787 was 103.1 +/- 12.3 ml/min, and that of ceftazidime was 80.6 +/- 13.2 ml/min. The serum bactericidal activities were measured with the microdilution method of Stratton and Reller (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. One hour after administration, we measured mean reciprocal bactericidal titers of SCE-2787 and ceftazidime, respectively, against Escherichia coli of 388 and 243, against Klebsiella pneumoniae of 395 and 138, against Pseudomonas aeruginosa of 13.0 and 12.7, and against Staphylococcus aureus of 32.2 and 4.0. No severe side effects were observed in this single drug administration.

Adult↗
PubMed1992

Synthetic human tRNA(UUULys3) and natural bovine tRNA(UUULys3) interact with HIV-1 reverse transcriptase and serve as specific primers for retroviral cDNA synthesis.

Full-length and 5'-truncated variants of human (h) tRNA(UUULys3) were synthesized by in vitro transcription using SP6 RNA polymerase. Bovine(b) tRNA(SUULys3) was purified from calf liver. Both full-length tRNA species were shown to be biologically active in an aminoacylation assay. Gel retardation assays revealed that both full-length tRNA species, as well as a 5'-truncated h-tRNA(UUULys3) molecule containing 24 nucleotides (nt) at the 3' end (Lys24), interact with human immunodeficiency virus (HIV)-1 reverse transcriptase (RT). Competition studies with these three tRNA species demonstrate that the 3' end of h-tRNA(UUULys3) contributes to the interaction with HIV-1 RT. Escherichia coli tRNA(UUULys) and tRNA(UUCGlu2) were also able to interact with the enzyme, whereas unrelated RNA molecules such as E. coli 5S rRNA did not bind to RT. Both b-tRNA(SUULys3) and h-tRNA(UUULys3) molecules, as well as the 5'-truncated variants, could be demonstrated to prime cDNA synthesis specifically using a HIV-1 RNA template, prepared by in vitro transcription, indicating that other viral or cellular proteins are not essential for this process. E. coli tRNA(UUULys) and tRNA(UUCGlu2), although able to interact with HIV-1 RT, failed to prime retroviral transcription. Products of cDNA synthesis were characterized by polymerase chain reaction, demonstrating that at least 18 nt at the 3' ends of h-tRNA(UUULys3) and b-tRNA(SUULys3) are still present in the cDNA product, whereas the 5' ends of both primer molecules were removed by the RNase H activity of HIV-1 RT.

Animals↗
PubMed1992

Isolation of Mycobacterium simiae from the environment.

An examination of 18 sphagnum samples collected in two different biotopes of the coastal region of southeastern Madagascar revealed an unexpectedly high positivity for mycobacteria (83.3%). The concentration of alcohol acid-fast bacilli reached a high level of 10(5) and 10(6)/g, respectively, compared with the sphagnum biotopes in moderate climates. Besides the habitat-specific mycobacterial species in sphagnum vegetation, like M. sphagni, M. gordonae and M. madagascariense, potentially pathogenic species, like M. avium, M. scrofulaceum and M. xenopi and M. marinum, were found. Furthermore, pathogenic M. simiae was found in sphagnum vegetation of Madagascar, first time isolated in the environment until now. It should be considered as a potential source of infection for human and animals.

Animals↗
PubMed1991

Clone pAT 133 identifies a gene that encodes another human member of a class of growth factor-induced genes with almost identical zinc-finger domains.

We report the structure and regulation of a gene represented by clone pAT 133, which is induced upon transition from a resting state (G0) through the early phase of the cell cycle (G1). The pAT 133 gene is immediately induced, with FOS-like kinetics, in human T cells and in fibroblasts. Primary structure analysis showed that the encoded protein contains three tandem zinc-finger sequences of the type Cys2-Xaa12-His2. This zinc-finger region, which is thought to bind DNA in a sequence-specific manner, is similar (greater than 80% on the amino acid level) to two previously described transcription factors pAT 225/EGR1 and pAT 591/EGR2. Except for the conserved zinc-finger domains, the amino acid sequences of the three proteins are distinct. This structural similarity suggests that the pAT 133 gene encodes a transcription factor with a specific biological function. Comparing the regulation of these related zinc-finger-encoding genes showed coordinate induction upon mitogenic stimulation of resting T lymphocytes and of resting fibroblasts. However, upon transition from a proliferating (G1) to a resting state of the cell cycle the three genes were differently regulated. In human histiocytic U937 cells mRNA of clone pAT 133 was constitutively expressed, whereas mRNA of pAT 225/EGR1 was induced upon induction of terminal differentiation. In contrast mRNA representing pAT 591/EGR2 was not expressed in these cells. This difference in gene regulation suggests distinct biological roles in the control of cell proliferation for the respective proteins.

Amino Acid Sequence↗
PubMed1991

Luminance-increment detection: capacity-limited or not?

Three experiments investigated whether spatial cuing influences luminance-increment detection accuracy. Ss saw multiple-target displays and responded yes or no to 4 locations, including cued position. To test whether cuing effects are due to the load on visual short-term memory from the number of locations, Experiments 1 and 2 presented displays with 4 or 8 relevant locations. Experiment 1 used peripheral cues; Experiment 2 used central cues. Significant cuing effects were less marked with 4- than 8-location displays. Cuing effects were largest with multiple targets, but a small reliable effect remained even with single targets. Experiment 3 replicated the single-target effect with predominantly multiple- and single-target displays. A capacity-limited selection account is developed for these findings and their implications are discussed for separate central and peripheral cuing mechanisms and the locus of spatial cuing effects.

Adult↗
PubMed1989

Age-related decrease in an early step of DNA-repair of normal human lymphocytes exposed to ultraviolet-irradiation.

A monoclonal antibody-based immunoassay has been used to detect age-related changes in the rate of loss of photoproduct antigenicity from the DNA of peripheral blood lymphocytes irradiated with 10 J m-2 uv-C. Lymphocytes were obtained from 75 healthy volunteers whose ages ranged from 14 months to 82 years. The samples were divided by age decades into groups of 10 individuals, except the first decade which contained only 5 individuals. The mean loss of antigenicity +/- 1 standard deviation was determined for each group at 10, 30, and 60 min after irradiation. The data were analyzed by Mann-Whitney U test and by the Kruskal-Wallis test. After a recovery period of 10 min the loss of antigenicity was most rapid in group I (0-9 years), less rapid in group II (10-19 years), and least rapid in all other groups. The differences between groups became less at 30 min and were not significant at 60 min incubation. These data obtained from normal cells concur with our previous conclusions, that reductions in the rate of loss of antigenicity in nondiseased cells isolated from patients with melanoma and dysplastic naevus syndrome reflect genetic abnormalities in these patients.

Adolescent↗
PubMed1989

Reflexive and voluntary orienting of visual attention: time course of activation and resistance to interruption.

To study the mechanisms underlying covert orienting of attention in visual space, subjects were given advance cues indicating the probable locations of targets that they had to discriminate and localize. Direct peripheral cues (brightening of one of four boxes in peripheral vision) and symbolic central cues (an arrow at the fixation point indicating a probable peripheral box) were compared. Peripheral and central cues are believed to activate different reflexive and voluntary modes of orienting (Jonides, 1981; Posner, 1980). Experiment 1 showed that the time courses of facilitation and inhibition from peripheral and central cues were characteristic and different. Experiment 2 showed that voluntary orienting in response to symbolic central cues is interrupted by reflexive orienting to random peripheral flashes. Experiment 3 showed that irrelevant peripheral flashes also compete with relevant peripheral cues. The amount of interference varied systematically with the interval between the onset of the relevant cue and of the distracting flash (cue-flash onset asynchrony) and with the cuing condition. Taken together, these effects support a model for spatial attention with distinct but interacting reflexive and voluntary orienting mechanisms.

Adult↗
PubMed1989

Spatial cueing and the relation between the accuracy of "where" and "what" decisions in visual search.

To study the processes underlying selective attention in visual search, the relation between the accuracy of "where" (location) and "what" (same/different orientation matching) decisions was analysed under various display conditions. Target-non-target discriminability was varied by contrasting single and multiple element displays; further, attention was directly manipulated by spatial cueing. In Experiment 1, analyses for both single and multiple displays showed that localization accuracy remained above chance when same/different matching failed; the inverse also obtained. It seems that accurate matching is not a prerequisite for target localization, nor is accurate localization a prerequisite for same/different matching. However, localization is a prerequisite for the accurate recognition of target orientation (Experiment 2). In this case, it seems that features critical for localization "call" attention to a particular candidate location. This facilitates further (shape) analysis of the stimulus that is found there. This orienting process is by-passed if attention is cued to the location in advance.

Adult↗
PubMed1989

Movement versus focusing of visual attention.

In two experiments, we investigated the idea that attention moves through visual space in an analog fashion. The spatial distribution of attention was determined by presenting a spatially informative cue and comparing reaction times to targets at cued and uncued locations as a function of the interval from cue onset to target onset (SOA). Facilitation and inhibition were measured by reference to a neutral condition in which the cue provided no spatial information. In the first experiment, we used a central cue (an arrow), and in the second experiment, we used a peripheral cue (a 50-msec flash). With central cue, the facilitatory effects of the cuing were initially equal for all locations on the indicated side of the display, and then decreased for all locations except the one that had been specifically cued. These results are interpreted as being more consistent with "focusing" of an initially broad "beam" of attention than with "movement" of a narrow beam from fixation to the cued location. With peripheral cues, strong facilitation specific to the cued location was manifest as early as 50 msec after cue onset, but this effect decreased with increasing SOA. Inhibition for uncued locations increased with increasing SOA at a rate that generally reflected their distance from the cued location. Taken together, these results reveal important differences between peripheral and central cues in the generation of attentional selectivity, not just in the time-course of events, but also in the nature of the processes involved.

Attention↗
PubMed1988

[Primary hyperparathyroidism with acute pancreatitis during pregnancy].

During her second pregnancy a 27-year-old woman had recurrent acute pancreatitis, in the course of which primary hyperparathyroidism was diagnosed. After regression of the acute signs and under conservative treatment a parathyroid tumour was removed in the 26th week of pregnancy. Comparison of surgical and conservative treatment of primary hyperparathyroidism during pregnancy has indicated that the risk of complications in the neonate is much lower after surgical removal of the adenoma than with an attempt to postpone by symptomatic drug treatment the parathyroidectomy until after delivery.

Acute Disease↗
PubMed1987

Chain length and pressure dependence of lipid translational diffusion.

The translational diffusion of pyrene, pyrene butyric acid and pyrene decanoic acid has been determined in phosphatidylcholine bilayers of different chain length and under pressure up to 200 bars. In the liquid crystalline phase and at a given temperature the diffusion decreases with increasing chain length. At a constant reduced temperature, Tred (about 10 K above the transition temperature), long chain lipids exhibit the fastest diffusion which is in disagreement with hydrodynamic models but favours free volume models for diffusion in lipid bilayers. The volume of activation, Vact, calculated from the decrease of the diffusion coefficient with pressure, delta lnD/delta P, depends on lipid chain length. Vact decreases with decreasing lipid chain length at a given temperature, T = 65 degrees C, and increases at the reduced temperature. These results are again in agreement with the dependence of the diffusion on lipid chain length and therefore with the free volume model.

Chemical Phenomena↗
PubMed1987

[Results of treatment following stage-dependent therapy of non-seminomatous testicular tumors].

The results of the treatment of 194 patients with non-seminomas were analyzed and statistically registered. The therapeutic approach is described and the cumulative probability of survival is compared according to the stages. For the total number of these tumours a cumulative 5-year-survival probability of 68.6% was calculated. In detail it reaches from 100% in clinical stage I to 39.7% in clinical stage III. The decisive change of the prognosis is between the clinical stages IIb and IIc. An adjuvant cytostatic therapy should, if performed, be aggressive. Relapses in the clinical stage I are possible and call for a critical valuation of the primary stage. A retarded cytostatic polychemotherapy should be performed only under certain conditions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Lateral diffusion of small solutes and partition of amphipaths in defect structures of lipid bilayers.

The excimer formation technique has been applied to investigate the mechanism of the lateral diffusion in the crystalline P beta' phase of dipalmitoylphosphatidylcholine vesicles. This became possible at low pyrene concentrations. From the shape of phase-transition curves, from the effect of pressure up to 150 bar and from the perturbation induced by cholesterol, we conclude that the free volume model could also be applied to the P beta' phase. However, the diffusion is thought to occur in defect structures that are considered to form fluid pathways between domains of crystalline lipid. Partition coefficients of amphipaths provide a basis for testing for the role of defects. The amphipath chlorpromazine partitions into fluid membranes with a partition coefficient, kp, of 3200, into the crystalline phase with kp = 200 but into the P beta' phase with a value of kp = 800. This again gives rise to the assumption that the P beta' phase contains fluid domains that behave like the fluid L alpha phase and make up about 10-20% of the total amount of lipid in the bilayer. Cholesterol is known to interfere especially with defect structures in the P beta' phase. It fills up the gaps, and therefore reduces the partition coefficient to almost zero in the P beta' phase.

Chlorpromazine↗
PubMed1986

Idiotypic selection of an antibody mutant with changed hapten binding specificity, resulting from a point mutation in position 50 of the heavy chain.

Somatic mutation occurs at a low rate in the rearranged antibody V region genes of the hybridoma line B1-8. delta 1 which expresses an antibody with specificity for the hapten 4-hydroxy-3-nitro-5-iodo-phenylacetyl (NIP). A mutant was selected which had lost a binding site-related idiotope but retained most of its other idiotypic determinants. The mutant had concomitantly lost NIP binding and acquired specificity for dinitrophenylated bovine serum albumin. It carried a single point mutation in position 50 of the heavy chain, resulting in the replacement of an arginine by a glycine.

Amino Acid Sequence↗
PubMed1985

Increased prevalence of minor anomalies in childhood malignancy.

Body measurements were taken and the prevalence of major malformations and of 57 minor anomalies was determined in 106 children with malignant disease, in 81 of their sibs, and in 106 control subjects matched to the patients according to sex, age and ethnic origin. Leukaemic children had a significantly smaller head circumference than the corresponding control children, but no significant differences in height, weight, anthropometric and syndromologic indices were found. No differences were observed in the frequency of associated major malformations including renal malformations detectable by sonography. The prevalence of minor anomalies was significantly higher in the patients with malignant disease and their sibs than in the control children: 69.2% of the patients, 63.0% of the sibs and 34.6% of the control subjects had at least one minor anomaly. When two and more minor anomalies were considered, the prevalence figures were 36.5%, 29.6% and 12.5%, respectively. Among the single minor anomalies only the Sydney line was significantly more frequent in patients with solid tumours. No specific association of an individual dysplasia or a pattern of minor anomalies with a given tumour could be established.

Adolescent↗