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Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 1,063 records · Page 59Linked to original sources
PubMed1991

Frequency representation in the rat cochlea.

In order to determine the place-frequency map of the rat cochlea, iontophoretic HRP-injections were made into the cochlear nucleus at electrophysiologically characterized positions. Distribution of retrograde HRP transport in cochlear spiral ganglion cells was analysed by means of a three dimensional reconstruction of the cochlea. The map was established for frequencies between 1.2 and 54 kHz, corresponding to positions between 96.5 to 2% of basilar membrane length (base = 0%). At apex of the cochlea the slope of the place-frequency map was below 0.25 mm/octave. The slope increased to a value of 2.1 mm/octave at 34% basilar membrane length, and remained almost constant towards the cochlear base. The close relationship between frequency range of highest sensitivity and maximum receptor- and innervation-density in the rat cochlea is discussed.

Acoustic Stimulation↗
PubMed1991

Relationship between tone burst discharge pattern and spontaneous firing rate of auditory nerve fibres in the guinea pig.

A detailed investigation was carried out of the response of single auditory nerve fibres in the guinea pig to tone bursts. Comparisons were made between the shapes of peri-stimulus-time histograms (PSTHs) of low and high characteristic frequency (CF) fibres grouped according to their spontaneous firing rates (SR). Both low and high CF fibres of high spontaneous rate (greater than 18 spikes/s) exhibited marked rapid adaptation in their PSTH's which became most pronounced at high stimulus intensities. The ratio of onset-to-adapted firing estimated from PSTH data in these fibres increased monotonically as a function of adapted firing rate. The behaviour of fibres with the lowest spontaneous rates (less than 0.5 spikes/s) was markedly different, particularly in fibres from low CF regions. In general, these low-SR fibres showed slower adaptation than high-SR fibres, and a less pronounced onset peak. This was most striking in low CF fibres. Furthermore, the ratio of onset-to-adapted firing rate tended to decrease with increasing stimulus intensity in both low and high CF fibres with low spontaneous firing rates. Low-SR fibres also showed the highest maximum discharge rates to tone burst stimuli. Fibres with medium spontaneous rates between 0.5 and 18 spikes/s displayed intermediate characteristics in their PSTH's. Recent data in the chinchilla (Relkin and Doucet, 1991), suggest that these differences may arise in part from differences in inter-stimulus recovery processes in the different spontaneous rate groups.

Acoustic Stimulation↗
PubMed1991

Shapes of rate-versus-level functions of primary auditory nerve fibres: test of the basilar membrane mechanical hypothesis.

Rate-versus level functions (RI functions) for characteristic frequency (CF) stimulation were measured from primary auditory nerve fibres from different spontaneous rate categories in the guinea pig cochlea. Attention was focussed on those fibres that showed clear breakpoints in their RI functions (sloping-saturation fibres). A statistical curve fitting procedure to an empirical equation was used to provide a quantitative estimate of the breakpoint position in individual fibres. It was found that, within the limits of reliability of the curve fitting procedure, the breakpoint position was the same in fibres from the same CF regions in any given animal. This result is consistent with the notion that the breakpoint position is determined by global basilar membrane mechanics and not by processes private to each nerve fibre. However, a subgroup of fibres not easily classifiable as sloping-saturation, showed features of their RI functions suggesting that factors other than basilar membrane mechanics could lead to fibre-to-fibre differences in rate-versus-level behaviour.

Acoustic Stimulation↗
PubMed1991

Rate-versus-level functions of primary auditory nerve fibres: evidence for square law behaviour of all fibre categories in the guinea pig.

Detailed measurements of rate-versus-level (RI) functions close to threshold were made from single primary auditory nerve fibres in the guinea pig cochlea. For all fibres, a simple square law provided the best statistical fit to the data near threshold, regardless of spontaneous fibrin rate of the fibre. In no case was a better fit obtained with an exponent greater than 2. We conclude that a simple square law is an accurate description of the underlying synaptic drive to all primary auditory nerve fibres. For fibres with very low spontaneous firing rates the best square law fit near threshold frequently led to the formal mathematical estimate of a negative firing rate as the asymptotic value of the spontaneous firing rate. The 'negative spontaneous rate' of low spontaneous rate fibres derived from curve fitting can be conceptualized by postulating that for sound pressures well below threshold in these fibres the underlying synaptic drive lies below a threshold value at a site determining action potential generation.

Acoustic Stimulation↗
PubMed1991

Developmental changes of frequency representation in the rat cochlea.

The place-frequency map of the developing rat cochlea was measured by iontophoretic HRP-injections into the ventral cochlear nucleus at electrophysiologically characterized positions. Distribution of retrograde HRP transport in cochlear spiral ganglion cells was analysed by means of a three dimensional reconstruction of the cochlea. Cochlear place-frequency maps were derived in rats of two ages groups: 13 to 22 days, and 36/37 day old animals. These maps were compared with the place-frequency map of adult rats (Müller, 1991). No systematic difference in the place-frequency map between 36/37 day old and adult rats was observed. In animals of the younger age group the place-frequency map (for frequencies above 4 kHz) was shifted towards lower frequencies for a given place along the basilar membrane. The morphological and physiological basis for this frequency shift during development is discussed.

Acoustic Stimulation↗
PubMed1991

Frequency representation and spiral ganglion cell density in the cochlea of the gerbil Pachyuromys duprasi.

The tonotopic map of the cochlea in the gerbil Pachyuromys duprasi was analysed by local iontophoretic HRP-application into physiologically defined regions of the cochlear nucleus and mapping of subsequent HRP transport patterns in cochlear spiral ganglion cells. Furthermore the spiral ganglion cell density along the cochlear duct was determined. The cochlear tonotopic map was established in the frequency range between 0.6 and 17.5 kHz. These frequencies corresponded to locations between 86 and 3% basilar membrane length (0% = cochlear base). It was found that the slope of the place-frequency map varied with frequency, the maximum slope being found between 1 and 4 kHz. This frequency range corresponds to the frequency range of highest auditory sensitivity as determined from cochlear microphonic recordings (Plassmann et al., 1987). The density of spiral ganglion cells also varied along the cochlear duct. A pronounced maximum (1927 cells/mm) was located at around 70% basilar membrane length, compared to values of 800 cell per mm near the cochlear apex and base. This region of high ganglion cell density also corresponds to the frequency range of highest auditory sensitivity.

Acoustic Stimulation↗
PubMed1991

High precision immunoscanning electron microscopy using Fab fragments coupled to ultra-small colloidal gold.

Ultra-small colloidal gold (less than 1 nm), bound to Fab fragments provides the shortest practical specific marker system to date and can be used in concert with field emission scanning electron microscopes to precisely locate antigenic sites. An "in-lens" FE-SEM equipped with a highly sensitive single crystal YAG-detector for backscattered electrons, as well as the use of advanced specimen preparation techniques based on cryofixation, are among the indispensible prerequisites. A T-even type Escherichia coli bacteriophage, Tu II*-46, was chosen to study properties of the immunogold labeling system. Distinct regions on the tail fibers of this phage were labeled with Fab fragments derived from antibodies against the related phage Tu II*-6. The tail fibers are composed of pairs of homologous proteins, thus offering two identical antigenic sites at the same locus on the tail fibers. Fab fragments can be visualized in the SEM at high accelerating voltage (30 kV) without any additional marker. This permits comparison of the labeling characteristics of unmarked and colloidal gold-marked Fab fragments. Unmarked Fab fragments often bind by pairs (two singlet Fab fragments bound opposed to each other along the axis of the tail fiber). The labeling efficiency of unmarked Fab fragments was greater than that of ultra-small gold-labeled Fab fragments. Binding by pairs was not seen after labeling with ultra-small gold-Fab fragments. The conjugates used in this study exhibited one colloidal gold per Fab fragment.

Animals↗
PubMed1991

Physiological, morphological, and physicochemical characterization of a novel Escherichia coli bacteriophage, phage MM.

A double-stranded DNA containing, T even-like, Escherichia coli bacteriophage, called MM, has been isolated from the local sewage and purified by polyethylene glycol precipitation followed by banding on a cesium chloride three-step gradient. It yields a burst size of 75 particles per infected cell, and has an adsorption coefficient of 3.3 x 10(-10) cm3/min and a latent period of 45 min. Electron microscopy of phage MM reveals an isometric icosahedral head, 92 nm long and 81 nm wide, and a 112-nm-long contractile tail with six pairs of 40-nm-long fibers attached to its baseplate. Phage MM appears similar to E. coli phage T4 or Salmonella phage O1. The density of phage MM in cesium chloride is 1.515 g/ml, and its total mass is 144 MDa. Gel electrophoresis of purified MM capsids displays two major capsid proteins in approximately equimolar amounts and with apparent molecular masses of 38 and 15 kDa. Similarly, purified MM tails yield two major polypeptides with apparent molecular masses of 55 and 16 kDa, most likely representing the major tail sheath and tail tube polypeptides. Its double-stranded DNA has a G-C content of 50%, a length of 131 kilobases (kb), and a mass of 89 MDa.

Adsorption↗
PubMed1991

Pattern of NADPH-diaphorase active neurons in rat forebrain is unchanged after pentylenetetrazol kindling.

The activity of NADPH-diaphorase in rat telencephalic structures has been revealed by use of a histochemical method. Multiple neurons belonging to different nuclei were found to contain the enzyme. Furthermore, diaphorase reactive nerve fibres and terminal fields were observed to be widely distributed throughout rat brain. Chemical kindling induced by pentylenetetrazol (PTZ) did not effect the regional distribution and cellular localization of the enzyme in the rat CNS.

Animals↗
PubMed1991

Congenital esophagostenosis.

By means of two of our own cases we report on congenital esophagostenosis which occurs in a proportion of 1:50,000. The typical clinical symptoms consist of frequent vomiting, regurgitation of undigested food particles which have no acid smell, and regurgitation of viscous mucus and saliva. In the last decade direct operative treatment has taken the place of primary bougienage therapy.

Esophageal Stenosis↗
PubMed1991

Adult rat cardiomyocytes cultured in creatine-deficient medium display large mitochondria with paracrystalline inclusions, enriched for creatine kinase.

In adult regenerating cardiomyocytes in culture, in contrast to fetal cells, mitochondrial creatine kinase (Mi-CK) was expressed. In the same cell, two populations of mitochondria, differing in shape, in distribution within the cell and in content of Mi-CK, could be distinguished. Immunofluorescence studies using antibodies against Mi-CK revealed a characteristic staining pattern for the two types of mitochondria: giant, mostly cylindrically shaped, and, as shown by confocal laser light microscopy, randomly distributed mitochondria exhibited a strong signal for Mi-CK, whereas small, "normal" mitochondria, localized in rows between myofibrils, gave a much weaker signal. Transmission EM of the giant mitochondria demonstrated paracrystalline inclusions located between cristae membranes. Immunogold labeling with anti-Mi-CK antibodies revealed a specific decoration of these inclusions for Mi-CK. Addition of 20 mM creatine, the substrate of Mi-CK, to the essentially creatine-free culture medium caused the disappearance of the giant cylindrically shaped mitochondria as well as of the paracrystalline inclusions, accompanied by an increase of the intracellular level of total creatine. Replacement of creatine in the medium by the creatine analogue and competitor beta-guanidinopropionic acid caused the reappearance of the enlarged mitochondria. It is believed that the accumulation of Mi-CK within the paracrystalline inclusions, similar to those observed in certain myopathies, represents a compensatory effect of the cardiomyocytes to cope with a metabolic stress situation caused by low intracellular total creatine levels.

Animals↗
PubMed1991

Skp is a periplasmic Escherichia coli protein requiring SecA and SecY for export.

Skp of Escherichia coli (OmpH of Salmonella typhimurium) is a protein whose precise function has been obscured by its ubiquity in a wide range of subcellular fractions such as those containing DNA, ribosomes, and outer membranes. Combining in vitro and in vivo techniques we show that Skp is synthesized as a larger precursor that is processed upon translocation across the plasma membrane. Translocation is dependent on the H(+)-gradient, ATP, SecA, and SecY. Upon cellular subfractionation (avoiding non-specific electrostatic interactions) Skp partitions with beta-lactamase into the fraction of soluble, periplasmic proteins. In the context of the export factor properties of Skp previously demonstrated in vitro it is conceivable that this protein is involved in the later steps of protein translocation across the plasma membrane and/or sorting to the outer membrane.

Adenosine Triphosphatases↗
PubMed1991

Doppler CO2-test in patients with vertebrobasilar ischemia.

The pathogenesis of vertebrobasilar ischemia (VBI) is still uncertain. Embolism and systemic hypotension have been discussed as possible causes. We evaluated the basilar arteries of 35 VBI-patients by transcranial Doppler-sonography at rest and under hypercapnic conditions and compared these findings with the basilar flow velocities in 10 healthy volunteers matched by age. We found no difference between the controls and the VBI-patients for the basilar flow velocities at rest. Under hypercapnia (end-tidal CO2-concentration 8.5%), the basilar blood flow velocities in the healthy controls increased by an average of 53.0% but only by 32.3% in the VBI-patients (p less than 0.005). The reduction of CO2 dependent vasomotor reactivity was observed in all VBI-patients, except in patients with infarction in the posterior cerebral artery area, possibly indicating a different pathogenic mechanism of stroke. The results in all other patients revealed no obvious correlation to the clinical course or angiographic or dopplersonographic findings. As CO2 dependent vasomotor reactivity and brain perfusion pressure dependent cerebral autoregulation have similar mechanisms, we conclude that systemic hypotension might play an important part in VBI.

Aged↗
PubMed1991

Human papillomavirus type 18 E6 and E7 antibodies in human sera: increased anti-E7 prevalence in cervical cancer patients.

Antibody-reactive regions on the human papillomavirus type 18 (HPV-18) E6 and E7 proteins were identified with rabbit polyclonal anti-fusion protein sera by screening of an fd phage expression library containing subgenomic HPV-18 DNA fragments and by testing of overlapping decapeptides representing the E6 and E7 open reading frames. Peptides comprising the delineated regions (designated E6/1 to E6/4 and E7/1) were synthesized and used in an enzyme-linked immunosorbent assay (ELISA) to detect anti-HPV-18 antibodies in human sera. A total of 232 human serum samples (identical numbers of cervical cancer patients and age-matched controls) collected in Tanzania were tested. Similar prevalences (between 0.8 and 4.3%) of antibodies recognizing the different E6 peptides were found in the sera from tumor patients and controls. With a synthetic 28-mer peptide (designated pepE701) comprising the E7/1 region, a significant difference was found: 10 of 116 tumor serum samples but 0 of 116 control serum samples showed a specific reaction (P less than 0.001). This observation confirms earlier results with HPV-16 E7 fusion proteins (I. Jochmus-Kudielka, A. Schneider, R. Braun, R. Kimmig, U. Koldovsky, K. E. Schneweis, K. Seedorf, and L. Gissmann, J. Natl. Cancer Inst. 81:1698-1704, 1989). A lower prevalence of anti-HPV-18 E7 antibodies was observed when 188 human serum samples collected in Germany from tumor patients and controls were tested (3 of 94 positive in the cancer group; 0 of 94 positive in the control group). The type specificity of anti-HPV-18 E7 antibodies was demonstrated when the HPV type found by Southern hybridization in the cervical cancer biopsies was compared with seroreactivity: 4 of 8 serum samples obtained from HPV-18 DNA-positive but 0 of 16 serum samples from HPV-18 DNA-negative tumor patients reacted in the HPV-18 E7 ELISA. In addition, HPV-18-positive sera failed to react in a peptide ELISA with the homologous HPV-16 E7 region (M. Müller, H. Gausepohl, G. de Martinoff, R. Frank, R. Brasseur, and L. Gissmann, J. Gen. Virol. 71:2709-2717, 1990) and vice versa.

Amino Acid Sequence↗
PubMed1991

A mammary-specific promoter directs expression of growth hormone not only to the mammary gland, but also to Bergman glia cells in transgenic mice.

The whey acidic protein (WAP) promoter has been previously used to target the expression of heterologous genes to the mammary glands of transgenic mice. To direct the expression of human GH (hGH) to mouse mammary glands, hGH-coding sequences have been coupled to WAP promoter sequences (WAP-hGH). Female transgenic mice carrying the WAP-hGH constructs show expression of hGH in the mammary gland, demonstrating the functionality of the transgenes. However, when other organs from these transgenic mice were examined, high level expression of hGH was unexpectedly observed in the brains of all male and female mice. Using in situ hybridization or immunohistochemistry, hGH expression from the transgene was seen to occur specifically in Bergman glia cells. In contrast, mice carrying hGH-coding sequences linked to the metallothionein promoter do not express hGH in these cells. Neither the endogenous WAP gene nor at least three other transgenes in which heterologous genes have been placed under the transcriptional control of the WAP promoter are expressed in the brain. Thus, we propose that the combination of the WAP promoter and the hGH structural gene results in a novel tissue specificity in the Bergman glia.

Animals↗
PubMed1991

Changes of antioxidative homeostasis in patients on chronic haemodialysis.

The balance between reactive oxygen species (ROS) generated during metabolism and their scavengers and trappers is changed in patients on chronic haemodialysis. Recently we found an increased superoxide anion-trapping capacity of uraemic serum before haemodialysis which was decreased during the treatment, probably because of loss of antioxidants into the dialysate. In this study the generation of superoxide anions by polymorphonuclear leukocytes (PMN) was examined. There was a tendency for decreased ROS generation during transient leukopenia regarding all conditions of PMN incubation and stimulation. The changed antioxidative homeostasis is thought to be one factor of decreased red blood cell (RBC) survival and thereby of renal anaemia in patients on chronic haemodialysis. Our results support this hypothesis, indicating an increased haemolysis ratio of RBC after haemodialysis in a strongly artificial singlet oxygen stress.

Adult↗