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Biomedical subjects

R Müller

Publications and source records attributed to R Müller.

At least 343 records · Page 19Linked to original sources
PubMed1994

Crystallization and preliminary X-ray analysis of wild-type and K272A mutant glutamate 1-semialdehyde aminotransferase from Synechococcus.

Crystals of the pyridoxal-5'-phosphate dependent enzyme glutamate-1-semialdehyde aminotransferase (EC 5.4.3.8) from Synechococcus have been grown from polyethylene glycol solutions. The wild-type enzyme crystallizes in space group P2(1)2(1)2(1), with cell dimensions a = 68.4 A, b = 108.0 A, c = 122.6 A. The inactive mutant in which the cofactor-binding lysine 272 residue is replaced by alanine (K272A) gives monoclinic crystals of space group P2(1) with cell dimensions a = 67.1 A, b = 108.6 A, c = 124.5 A and beta = 115.7 degrees. These crystal forms diffract to 2.4 A and 2.7 A resolution, respectively.

Crystallization↗
PubMed1994

A novel member of human tissue inhibitor of metalloproteinases (TIMP) gene family is regulated during G1 progression, mitogenic stimulation, differentiation, and senescence.

We have identified in the human diploid fibroblast cell line WI-38 a novel serum-inducible gene, mitogen-inducible gene 5 (mig-5), of the delayed-early class, which represents a new member of the family of human tissue inhibitors of metalloproteinases (TIMPs). The deduced Mig-5 protein shares the highest degree of homology with chicken TIMP-3 (74% identity) and is more distantly related to human TIMP-1 and TIMP-2 (30-38% identity), indicating that mig-5 may represent the human homolog of chicken TIMP-3. In contrast to TIMP-1 and TIMP-2, mig-5 mRNA expression is not only induced in response to mitogenic stimulation but also is subject to cell cycle regulation in normally proliferating WI-38 fibroblasts and HL-60 myeloid cells, showing a clear peak around mid-G1. In agreement with this observation, differentiation of HL-60 cells to either granulocytic or macrophage-like cells leads to increased levels of mig-5 mRNA concomitant with a block in G1. In contrast, mig-5 expression is decreased in senescent human fibroblasts, suggesting that these cells may be blocked at a stage in G1 before or after the phase of maximum mig-5 expression. Since in contrast to the vast majority of other known mitogen-inducible genes, mig-5 expression is periodically up-regulated in G1, this gene should represent an invaluable tool for the analysis of cell cycle progression, terminal differentiation, and replicative senescence.

Amino Acid Sequence↗
PubMed1994

An autonomous N-terminal transactivation domain in Fos protein plays a crucial role in transformation.

To date, three functional domains have been defined in c-Fos and v-Fos proteins and have been shown to play a role in transactivation: the leucine zipper mediating hetero-dimerization, the basic DNA contact site, and a C-terminally located transactivation domain (C-TA) harbouring the HOB1 and HOB2 motifs. While the bZip region, consisting of the leucine zipper and the DNA contact site, is indispensable for transformation, the C-TA domain is not required and is actually altered by internal deletions in the FBR-MuSV. We now show that the N-terminal regions of c-Fos and v-Fos contain a second transactivation domain (N-TA). A functionally crucial motif within the N-TA domain, termed NTM, was pinpointed to a approximately 25 amino acid stretch around positions 60-84 which is highly conserved in FosB. Analysis of LexA fusion proteins showed that the N-TA domains of both c-Fos and FosB function in an autonomous fashion in both fibroblasts and yeast. Most importantly, deletion of the NTM motif impairs the transforming properties of v-Fos. Apart from the bZip region, the N-TA domain is the only functional domain required for transformation by v-Fos, at least when its expression is driven by the strong FBR-MuSV-LTR promoter.

3T3 Cells↗
PubMed1994

Different fate of sibling cells upon inhibition of transcription in G1.

In normally cycling populations of NIH3T3 cells, both sibling cells generated by a mitotic division require similar periods of time for completion of the cell cycle, with variations (intersibling times) of < or = 3 h for > 90% of the population. In this study, we analyzed by time-lapse video recording the effect of the RNA polymerase II inhibitor alpha-amanitin on the intersibling times of cells exposed to the drug at defined postmitotic ages. Our results led to the identification of three subpopulations of NIH3T3 cells. In the first one, both sibling cells were highly sensitive to alpha-amanitin. These cells were exposed to the inhibitor at a postmitotic age of < or = 2 h. The second subpopulation was composed of cells where one sibling showed normal kinetics of cell cycle progression, while the other sibling had an increased cell cycle length (intersibling times of up to 12 h) or did not divide at all during the period of observation. These cells were 2-8 h old at the time of treatment. In the third subpopulation, representing cells at later stages in the cell cycle, no significant increase in intersibling times was observed. These data indicate that alpha-amanitin increases the intersibling times of cells exposed to the drug during G1. In addition, our results suggest that the variable-length period of G1, thought to be located in late G1, is dependent on RNA polymerase II transcription.

3T3 Cells↗
PubMed1994

Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects.

In a single-blind, randomized, two-way cross-over study with 12 healthy male volunteers, 60 micrograms of prostaglandin E1 (PGE1) or placebo was administered by intravenous infusion during a 120-min period. PGE1, 13,14-dihydro-PGE1 (PGE0) and 15-keto-PGE0 plasma concentrations were measured by a highly specific and sensitive GC-MS/MS method. Endogenous PGE1 plasma concentrations ranged between 1.2 and 1.8 pg.ml-1. Endogenous PGE0 and 15-keto-PGE0 plasma concentrations varied from 0.8 to 1.3 pg.ml-1 and from 4.2 to 6.0 pg/ml respectively. During intravenous infusion of PGE1, plasma PGE1 concentrations rose to a level twice as high as during the placebo infusion. In contrast, PGE0 plasma concentrations were 8 times higher during PGE1 infusion than during placebo infusion, and 15-keto-PGE0 plasma concentrations were 20 times higher. The new analytical method has thus been useful to describe the pharmacokinetics of PGE1 and its metabolites PGE0 and 15-keto-PGE0, during and after intravenous infusion of PGE1.

Adult↗
PubMed1994

Immediate physiological responses of healthy volunteers to different types of music: cardiovascular, hormonal and mental changes.

A group of 20 healthy volunteers [10 women, 10 men; median age 25 (20-33) years] were examined by means of pulsed wave Doppler echocardiography, blood sample analysis and psychological testing before and after listening to three different examples of music: a waltz by J. Strauss, a modern classic by H. W. Henze, and meditative music by R. Shankar. To assess small haemodynamic changes, mitral flow, which reflects left ventricular diastolic behaviour, was measured by Doppler ultrasound. Heart rate, arterial blood pressure and plasma concentrations of adrenocorticotropic hormone, cortisol, prolactin, adrenaline, noradrenaline, atrial natriuretic peptide (ANP) and tissue plasminogen activator (t-PA) were determined simultaneously. Transmitral flow profile is characterized by early E-wave and late atrial induced A-wave. Velocity-time integrals were measured and the atrial filling fraction was calculated. The mental state was measured by using a psychological score (Zerssen) with low values (minimum 0) for enthusiastic and high values (maximum 56) for depressive patterns. Music by J. Strauss resulted in an increase of atrial filling fraction (AFF; 29% vs 26%; P < 0.05) and ANP (63 pg.ml-1 vs 60 pg.ml-1; P < 0.05). The mental state was improved (Zerssen: 6.5 vs 11 points; P < 0.05). After the music of H. W. Henze prolactin values were lowered (7.7 ng.ml-1 vs 9.1 ng.ml-1; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Characteristics of users of syringe vending machines in Berlin.

Vending machines providing sterile injection equipment are part of the AIDS prevention measures for injecting drug users (IDU) in Berlin. A study was carried out to assess characteristics (history of iv drug use, frequency of use of the machines, contact with counselling units for IDU, attitudes towards the machines, HIV serostatus) in users of syringe vending machines. Of the 313 individuals surveyed, 77% reported using the vending machines regularly (more than four times a week). Compared to other studies of IDU in Berlin (eg at syringe exchange programmes) the users of the vending machines had a significantly shorter history of iv drug use. Overall, 72% of the IDU had had contacts at some time with specialised agencies for counselling on drug abuse and AIDS; however, only 33% had such contacts currently. Sixty-five percent of the IDU commented critically on the machines or made suggestions for improvement; 18% had experienced that the machines did not always work well, 14% called for more machines. HIV seroprevalence based on self-reported test results (N = 252) was 20%. In multivariate statistical analysis positive HIV serostatus was associated with site of interview, longer history of intravenous drug use, and current contact with counselling agencies. Despite the ready availability of syringes and needles, 25% of the participants reported borrowing injection equipment from other IDU in the previous six months. This proportion was significantly higher in IDU younger than 25 years (39%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1994

Effect of contrast and adaptation on the perception of the direction and speed of drifting gratings.

Three experiments were conducted to analyse the effect of contrast and adaptation state on the ability of human observers to discriminate the motion of drifting gratings. In the first experiment, subjects judged the direction of briefly presented gratings, which slowly drifted leftward or rightward. The test gratings were enveloped in space by a raised cosine function and in time by a Gaussian. The centre of the spatial envelope was either 2 deg left or right of the fixation point. An adaptive staircase procedure was used to find the velocities, at which the observer judged the motion direction in 75% of the presentations as leftwards or rightwards, respectively. In the second experiment, subjects judged the relative speed of two simultaneously presented gratings. Stimulus contrast was varied in both experiments from 0.01 to 0.32. Discrimination threshold vs contrast functions were measured before and after adaptation to a high-contrast (0.4) grating drifting at rates between 2 and 32 Hz. In a third experiment, subjects matched, before and after adaptation, the relative speed of a test stimulus, which had a constant contrast (0.04 or 0.08) and a variable speed, to that of a reference stimulus having a variable contrast but a constant speed. The results indicate that, before adaptation, direction and speed discrimination thresholds are independent of test contrast, except when test contrast approaches the detection threshold level. Adaptation to a drifting grating increases the lower threshold of motion (LTM) and the speed discrimination threshold (delta V/V) for low test contrasts. In addition, the point of subjective stationarity (PSS) shifts towards the adapted direction and this shift is more pronounced for low test contrasts. The perceived speed of a drifting grating increases with increasing contrast level. Adaptation to a drifting grating shifts the perceived speed vs log contrast function downwards and to the right (toward higher contrast levels) and this shift is greatest for adaptation frequencies between 8 and 16 Hz. We further explored the effects of adaptation contrast (0.04, 0.4 and 0.9) and adaptation drift direction (iso- or contra-directional) on the perceived speed versus contrast function. The effect of adaptation is greatest for iso-directional drift and increases with increasing adaptation contrast. The results are discussed in terms of a contrast gain control model of adaptation.

Adaptation, Ocular↗
PubMed1994

Cholecystokinin-induced activity changes of dorsal lateral geniculate neurons in rats.

The effects of iontophoretically applied cholecystokinin fragments and cholecystokinin antagonists on neurons of the dorsal lateral geniculate nucleus were investigated with extracellular recordings in rats anesthetized with urethane. The peptide cholecystokinin-8S, which has affinity for both cholecystokinin-A and -B receptors, altered the baseline firing as well as the responses to visual stimuli of about one half of the investigated neurons (90 out of 190). Excitatory effects predominated (P < 0.01, Wilcoxon test), although inhibitory effects were also observed. The effects of cholecystokinin-8S were dose-dependent. Neurons sensitive to cholecystokinin-8S could be found in all regions of the dorsal lateral geniculate nucleus, but they differed in their susceptibility to cholecystokinin in relation to their location. The B-agonist, BOC-cholecystokinin-4, also changed the baseline firing as well as the light-evoked activity of dorsal lateral geniculate nucleus neurons. The effects were either excitatory or inhibitory. Changes induced by cholecystokinin-8S could be effectively blocked by the cholecystokinin-B antagonist, CAM 1028 (19 out of 22 cholecystokinin-sensitive neurons tested). The cholecystokinin-A antagonist, Ge 410, blocked cholecystokinin-induced effects in 10 out of 16 neurons. These results indicate that the modulation of geniculate cell firing by cholecystokinin is mediated by both A-and B-receptor types.

Animals↗
PubMed1994

Non-invasive bone biopsy: a new method to analyse and display the three-dimensional structure of trabecular bone.

Three-dimensional structure is one of the main factors influencing the mechanical behaviour of cancellous bone. To analyse the trabecular bone structure non-destructively we used a peripheral QCT system and applied a special thin-slice technique to create high-resolution volumetric data sets serving as a basis for something we would like to call non-invasive bone biopsy. In order to obtain binary data sets, the mineralized bone in the CT volume was separated from bone marrow and muscle tissue with the help of a sophisticated three-dimensional segmentation algorithm based on the analysis of directional derivatives, which are computed from a locally approximated fit function of the original CT volume. Binary volumes including either a solid representation of trabecular plates and rods or a topological representation of the cancellous bone architecture were acquired. Such volumes can be processed non-destructively and, even more important, repetitively. By using a surface reconstruction algorithm based on interpolating triangulation it was possible to visualize the three-dimensional surface of the trabecular bone structure. The results showed that surface representation and visualization in combination with a multiple thin-slice measuring technique are valuable tools in studying three-dimensional bone architecture. In the future, the non-invasive bone biopsies will be evaluated by means of three-dimensional mechanical analysis incorporating finite element modelling and direct morphological investigations of the cancellous bone architecture for a better prediction of bone strength as an index for fracture risk or osteoporosis.

Biopsy↗