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A Müller

Publications and source records attributed to A Müller.

At least 379 records · Page 21Linked to original sources
PubMed1994

Molecular analysis of the biosynthesis pathway of the alpha-2,8 polysialic acid capsule by Neisseria meningitidis serogroup B.

The genes encoding all enzymes necessary for capsular polysaccharide biosynthesis in Neisseria meningitidis B are located on a 5 kb DNA fragment within the chromosomal cps gene cluster. Nucleotide sequence analysis revealed four open reading frames (ORFs), which can encode proteins with molecular masses of 41.4 kDa, 24.9 kDa, 38.3 kDa, and 54.4 kDa, respectively. These ORFs constitute a transcriptional unit as demonstrated by Northern blots. Primer extension analysis revealed that the transcriptional start site is preceded by a nucleotide sequence with homologies to the sigma 70 consensus promoter sequence of Escherichia coli. Functional analysis of the proteins encoded by the ORFs indicated that ORF2 encodes the CMP-NeuNAc synthetase, ORF3 encodes the NeuNAc condensing enzyme, and ORF4 encodes the alpha-2,8 polysialyltransferase. ORF1 encodes an enzyme, which provides a precursor molecule for synthesis of monomeric NeuNAc. In E. coli the subcloned ORFs 2-4 were able to synthesize a high-molecular-weight alpha-2,8 polysialic acid. In contrast, inactivation of ORF1 in the meningococcal genome resulted in a complete loss of capsule production. A regulatory enzyme, the CMP-NeuNAc hydrolase, which cleaves CMP-NeuNAc to CMP and NeuNAc, was not found as a part of the capsular polysaccharide biosynthesis gene operon or within the cps gene cluster.

Amino Acid Sequence↗
PubMed1994

Structural investigation of Cetrorelix, a new potent and long-acting LH-RH antagonist.

The new decapeptide SB-75 (INN: Cetrorelix) has been characterized as a potent antagonist of luteinizing-hormone releasing hormone (LH-RH). Such derivatives are of great medicinal interest owing to their potential application in areas such as hormone-dependent tumors, uterine fibroids, and in diseases and conditions which result from inappropriate hormone levels or which can be treated by suppression of estrogens. SB-75 is the subject of intensive ongoing clinical evaluation and is an accepted standard for the design of new LH-RH antagonists. We characterized SB-75 by means of modern MS and NMR techniques to demonstrate the significance of both sequencing methods on a complicated unnatural decapeptide. Our structural elucidations with nuclear Overhauser (NOE) experiments revealed clear evidence for a highly flexible molecule with no single predominant conformation even in sodium dodecyl sulfate (SDS) mimicking a cellular membrane.

Amino Acid Sequence↗
PubMed1994

Alpha B crystallin expression in response to hormone, oncogenes and stress.

alpha B crystallin is one of the major eye lens proteins and it is abundantly expressed in many non-lenticular tissues as well. The alpha B crystallin protein sequence is similar to that of small heat shock proteins and we could demonstrate that alpha B crystallin does indeed accumulate in response to heat shock and other forms of stress. Moreover, ectopic expression of alpha B crystallin establishes a state of thermotolerance. Glucocorticoid hormones activate the alpha B crystallin gene with a delayed kinetics. Induced expression of the Ha-ras oncogene accelerates hormone-mediated gene induction. A shorter promoter sequence is required for the ras supported hormone response. However, sustained Ha-ras oncogene expression attenuates glucocorticoid-triggered induction of the alpha B crystallin gene completely. Whereas the small heat shock protein Hsp27 is overexpressed in many human mammary carcinomas, we observed the frequent absence of alpha B crystallin in these tumors but not in the normal breast tissue. In contrast, overexpression of alpha B crystallin has been frequently observed in non-neuronal brain tumors.

Animals↗
PubMed1994

[Medical psychologic studies of drunken drivers. A critical discussion to the contribution by Jansen and Utzelmann in Blutalkohol 31, 249-259, 1994].

I am replying to the critical analysis by Jansen and Utzelmann of one of my essays (Blutalkohol 30, 65-95, 1993). I reject their arguments; this underpins, once again, the unsatisfactory prognosis of expert opinion on DWI-offenders. Emphasis should be placed on general preventive measures with rules for behaviour rather than on efforts of assessing the driver's personality, which seems more just only at first sight.

Alcoholism↗
PubMed1994

Lipid content of microparticulate (1-->3)-beta-D-glucan isolated from Saccharomyces cerevisiae.

The preparation of pharmaceutical grade (1-->3)-beta-D-glucans from Saccharomyces cerevisiae requires that the microparticulate glucans which are employed as the starting material for drug production be of the highest purity. Potential contaminants of the (1-->3)-beta-D-glucan isolation process are yeast cell wall lipids, which are frequently found in association with glucans. The lipid content of yeast-derived (1-->3)-beta-D-glucan during various stages of the isolation process by methyl esterification and total ion gas chromatography and mass spectrometry (GC-MS) was examined. Following sequential alkaline and acid hydrolyses, the total lipid content of (1-->3)-beta-D-glucan was 100.4 nmol/mg with 9-cis-C 18:1 fatty acid accounting for 45.3 nmol/mg glucan (45%). Following ethanol extraction of the (1-->3)-beta-D-glucan, lipid was not detected. Indeed, fatty acid methyl esters were not detectable by total ion GC-MS in all twelve samples investigated. These data demonstrate that the isolation process for yeast-derived (1-->3)-beta-D-glucan effectively reduces contamination by yeast cell wall lipids.

Cell Wall↗
PubMed1994

[Tetrahymena pyriformis--a cell test system for environmental medicine. The effect of harmful substances on the cell morphology of Tetrahymena pyriformis].

In the region of Middle Germany phenols and their derivatives are important toxicological compounds for the environment and man. These compounds from wastes water of brown coal mining are source of danger, which can't estimate now. The influence of phenolic compounds on cells and organisms will be investigated with a species of ciliates-Tetrahymena pyriformis as testing system. T. pyriformis is a single-celled eucaryotic organism, which is comparable in sensitiveness and responsiveness to human tissue cells. That's why this cell system is very suitable to investigate on the influence of environmental pollutants. In our investigations phenol and 2,3-Dichlorophenol were used. Both compounds have a very toxic effect on cells. The toxicity of 2,3-Dichlorophenol is 50 times higher than the toxicity of pure phenol. Investigations of vitality by turbidimetry and morphology by image analysis have show that these compounds had an complex of the organisms.

Animal Testing Alternatives↗
PubMed1994

[Postoperative management after cesarean section--infusion therapy and role of intestinal stimulation with parasympathomimetic drugs and dexpanthenon].

In the last decade the incidence of cesarean section has raised worldwide to 15-30% of all deliveries. A standardized postoperative protocol can be applied to most cases and it should be easy to handle and at low costs. In the present randomized, prospective study 76 consecutive patients who hat a cesarean section were investigated. Two different infusion therapy protocols were compared and the role of prophylactic stimulation of peristalsis by parasympathometic drugs and by the pantothenic acid derivative dexpanthenon was evaluated. In group A patient (n = 36) were treated postoperatively with intravenous glucose 5% plus electrolytes and received routinely neostigmine and dexpanthenon, while patients in group B (n = 40) were treated with standardized commercially available solutions without intravenous stimulation of the bowel. Both groups were similar in terms of age, parity, gestational age, past medical history and previous abdominal surgery. The volume of urine and the serum electrolyte levels were similar in both groups postoperatively. The first evacuation of the bowel occurred in most cases on day 3 (A = 69.5%, B = 82.5% of the patients). 50% of the patients in group A complained of abdominal discomfort and pain postoperatively and needed some therapy, while in group B only 22.5% of the cases hat similar complaints. This difference was statistically significant (chi 2 Test: p < 0.02). The present data suggest that prophylactic postoperative stimulation of the peristalsis after cesarean section increases the incidence of abdominal discomfort significantly without influencing the bowel function. Standardized solutions can be used mostly for immediate intravenous fluid replacement and oral intake can be started after 2-6 hours.

Adult↗
PubMed1993

Studies on the inhibitory action of mercury upon proteinase K.

In proteinase K, Cys73 is located "below" the imidazole of the active site His69. In a 2.4-A resolution x-ray crystal structure of the complex formed between the enzyme and HgAc2, two Hg(II) positions are found: a fully occupied site, covalently bound to Cys73 (S gamma), which disrupts the catalytic triad (Asp39-His69-Ser224), and a 2-fold disordered (25 and 35% occupancy), noncovalent complexation to His72, Cys73, and Thr76 of lower affinity. The enzyme is inhibited noncompetitively at low concentrations and competitively above stoichiometric concentrations of Hg(II), but it retains 7% residual activity. This can be rationalized if the molecule is flexible enough to permit transient formation of the catalytic triad. Except for the active site, only minor structural changes are observed upon binding of Hg(II), but the thermal stability is reduced by 4 degrees C.

Binding Sites↗
PubMed1993

Both isoforms of protein phosphatase Z are essential for the maintenance of cell size and integrity in Saccharomyces cerevisiae in response to osmotic stress.

The sequences of two genes encoding the protein-serine/threonine-phosphatases PPZ1 and PPZ2 from Saccharomyces cerevisiae have been determined. The molecular masses of PPZ1 and PPZ2 are 77.5 and 78.5 kDa, respectively, and each protein consists of two distinct domains. The C-terminal half of each molecule is 93% identical in PPZ1 and PPZ2, and comprises the protein-phosphatase catalytic domain, while the N-terminal halves, which are rich in serine and asparagine (PPZ1) or serine and arginine (PPZ2), are only 43% identical. Both N-termini start with the amino acids Met-Gly-Asn, suggesting that after removal of the initiating methionine, the N-terminal glycine of the mature protein is myristoylated. Disruption of the gene encoding either PPZ1 or PPZ2 leads to an increase in cell size and cell lysis, the latter being more pronounced in cells disrupted in PPZ1. Haploid cells carrying a double disruption of PPZ1 and PPZ2 genes also show a marked increase in cell size and cell lysis, which can be significantly reduced by the addition of 1 M sorbitol to the growth medium. These results suggest that PPZ1 and PPZ2 play a role in regulating osmotic stability.

Alleles↗
PubMed1993

The in-vivo identification of the MoFe protein (FeMo cofactor) of nitrogenase in Klebsiella pneumoniae and of the Mo-storage protein in Azotobacter vinelandii via the nuclear quadrupole interaction of 99Mo(beta-)99Tc.

The expression of the MoFe protein of nitrogenase in Klebsiella pneumoniae was identified in vivo via the nuclear quadrupole interaction (NQI) of 99Mo(beta-)99Tc using perturbed angular correlations of gamma-rays. The NQI parameters were: omega approx. 360 Mrad/s and eta approx. 1. In addition, the NQI of the 'Mo-storage protein' in Azotobacter vinelandii cells which had been grown in the presence of NH4+ (13 mM), i.e. under conditions of strict repression of nitrogenase synthesis, was determined: omega approx. 190 Mrad/s, eta approx. 0.25. Under these conditions, the characteristic signal of the MoFe protein (FeMo cofactor) was absent.

Azotobacter vinelandii↗
PubMed1993

Detection of the in vivo incorporation of a metal cluster into a protein. The FeMo cofactor is inserted into the FeFe protein of the alternative nitrogenase of Rhodobacter capsulatus.

The photosynthetic bacterium Rhodobacter capsulatus has, in addition to the Mo nitrogenase, a second Mo-independent nitrogen-fixing system, an 'iron-only' nitrogenase which is strongly repressed by molybdate. The MoO4(2-) concentration causing 50% repression of the alternative nitrogenase in nifHDK- cells was 6 nM. If MoO4(2-) was added to a growing nifHDK- culture which had already expressed the alternative nitrogenase, the production of ethane from acetylene, by whole cells, was stimulated dramatically. In spite of the fact that C2H4 formation decreased continuously during the duration of the experiment (3 days), the total C2H6 production increased about twofold within the first 24 h, whereas the relative yield of C2H6 increased from 2% (C2H6/C2H4 x 100) in the absence of MoO4(2-), to a maximal value of 69% in the presence of MoO4(2-) (1 mM) after 72 h incubation. This 'Mo effect' appeared to be stronger the higher the MoO4(2-) concentration in the medium and the longer the incubation time. In the presence of ReO4-, WO4(2-) or VO4(3-), a similar effect did not occur. The 'Mo effect' was not observed in a nifHDK- nifE- double mutant which is unable to synthesize the FeMo cofactor and was diminished in a nifHDK- nifQ- mutant. Crude extracts from nifHDK- cells cultivated in the presence of MoO4(2-), also showed enhanced production of ethane. Component 1, purified from those extracts, displayed an S = 3/2 EPR signal which was relatively weak but characteristic for the FeMoco. These results strongly support the suggestion that the 'Mo effect' is a consequence of the formation of a hybrid enzyme consisting of the apoprotein of the alternative nitrogenase and the FeMo cofactor of the conventional nitrogenase. The 'Mo effect' was not influenced by the addition of chloramphenicol to the cultures. The occurrence of the 'Mo effect' appeared, therefore, to be independent of de-novo protein synthesis. The analysis of nifE-lacZ and nifN-lacZ fusions proved that both genes necessary for the FeMo cofactor synthesis are also expressed under conditions of MoO4(2-) deficiency. The possible explanations for incorporation of the FeMoco into component 1 of the alternative nitrogenase are discussed.

Chloramphenicol↗
PubMed1993

[Turcot syndrome--a rare extra-intestinal manifestation of familial adenomatous polyposis?].

The case of a 15-year-old male with Turcot syndrome is presented. When the patient was aged 10 years a medulloblastoma was diagnosed. Five years later he developed multiple adenomatous polyps of the colon and multiple "congenital hypertrophy of the retina" (CHRPE), the most common extraintestinal manifestation of FAP, were described. Family history revealed familial adenomatous polyposis with 12 family members exhibiting a FAP. The mode of inheritance of Turcot syndrome is controverted. Our case strengthens the hypothesis that the syndrome is a further extraintestinal (rare) manifestation of the FAP gene.

Adenomatous Polyposis Coli↗
PubMed1993

[Is there progress in preventive screening for colorectal carcinoma?].

Cost-benefit analysis for colorectal cancer-screening of asymptomatic patients has been discussed controversially. In patients with genetic predisposition for colorectal cancer, adenomatous polyps or resected cancer as well as inflammatory bowel disease in contrast the incidence of new cancer can be lowered by endoscopic surveillance. Newer techniques from molecular biology will in the near future permit to detect patients at risk with higher certitude and at an earlier time.

Adenomatous Polyposis Coli↗
PubMed1993

[Threatening thiamine deficiency in severe hyperemesis gravidarum].

We report the case of a patient with severe hyperemesis gravidarum. During parenteral nutrition the patient developed threatening thiamine deficiency. Wernicke's encephalopathy and tachycardia were predominant in the clinical course. Severe lactic acidosis and prolonged prothrombin time were the leading laboratory features. Thiamine deficiency as a cause of severe metabolic acidosis or coma can be easily ruled out or validated by intravenous thiamine administration.

Acidosis, Lactic↗
PubMed1993

Emergence of orientation selective simple cells simulated in deterministic and stochastic neural networks.

The processing of visual data in area 17 of the mammalian cortex is mainly performed by cells with receptive fields which are tuned to different orientations of input stimuli. The mechanisms underlying the emergence of receptive field properties of orientation selective cells are not well understood up to now. Recently, some models for the prenatal development of the receptive fields of orientation selective simple cells have been proposed, which emerge in neural networks trained by Hebb type unsupervised learning rules. These models, however, use different network architectures and are restricted to the case of identical input neurons. In this work, a biologically motivated neural network model with a general architecture is presented. It is trained with a Hebb type updating rule and with uncorrelated input. The input neurons are identified with retinal ganglion cells and exhibit mature Mexican hat type receptive fields. If the receptive fields of the input neurons have identical properties (deterministic model), a set of parameter domains is found, which characterize different kinds of receptive field maturation behaviour of the network. Results obtained by other authors with similar models are contained in this description as special cases. In addition, the more general and rarely investigated stochastic model, where random variations of the parameters describing the receptive fields of the input neurons occur, is investigated. A high sensitivity of the network against these random variations is obtained. In case of large variations of receptive field parameters of the ganglion cells, a qualitatively new kind of maturation behaviour appears. A significant part of the synaptic connections from ganglion cells to the cortical cell is removed and small simple cell receptive fields with only few lobes emerge. The stochastic model is found to provide a better description of the size, scatter and structure of receptive fields present in biological systems, than the deterministic model.

Animals↗