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J Müller

Publications and source records attributed to J Müller.

At least 145 records · Page 8Linked to original sources
PubMed2001

[Precancerous conditions and neoplasms of the anal area].

Classification of this lesions could be done concerning localisation and histological type. Squamous cell carcinoma of the anal canal are the most often to be found, but overall neoplasias in this region are very seldom. The most important role in pathogenesis seems to play infection with HPV viruses. Symptoms are in the beginning unspecific and similar to other common proctological diseases. Proctological diagnostic procedures are to be combined with cytological methods. Therapeutic management depends on malignant potential of the lesions and contains local excision, total operation and combined radiochemotherapy, which is today considered standard therapy of squamous cell carcinoma of the anal canal.

Anal Canal↗
PubMed2001

[Conservative therapy of incontinence].

Conservative therapy of faecal incontinence includes normalisation of colonic function, restauration of damaged anal skin and exercising methods. The most successful of those seems to be Biofeedback with good short time results up to 92% patients without further complaints, the long time results still being up to 67%. Prognosis depends on neuropathy, age and ability of perception and compliance. Passive electrostimulation replaces the damaged nerve and therefore has to be done lifelong. Increasing anal resting pressure seems to be a possible result.

Aged↗
PubMed2001

[Treatment of focal dystonia with botulinum toxin A].

Local injections with Botulinum toxin A (BtxA) are safe and effective in the treatment of focal dystonia. In cervical dystonia and blepharospasm, BtxA injections have become the treatment of choice. However, good results have also been reported with oromandibular dystonia, spasmodic dysphonia and writer's cramp. In cervical dystonia, muscles for injection are selected by clinical presentation or in complex forms with EMG guidance. Several studies have shown that 500 units Dysport are safe and effective in the treatment of cervical dystonia. In blepharospasm, injections are performed in the periorbital part of the orbicularis oculi muscle with good results for 12-14 weeks. The most frequently employed starting dose is 120 units Dysport per eye, divided in three periorbital injection sites. In case of levator inhibition, the pretarsal part of the orbicularis oculi muscle should be injected in a lower dose. EMG guidance is not necessary. By contrast, BtxA treatment of spasmodic dysphonia and writer's cramp require EMG-guided injections in order to avoid side-effects. Dose recommendations for the various types of dystonia are given in the text. In up to 5% of patients with dystonia, the development of neutralising antibodies is reported following repetitive injections with BtxA. Patients with antibodies had a shorter interval between injections, more "boosters", a higher dose per 3-month interval, and a higher total dose injected. In case of neutralizing antibodies against the A toxin, the treatment with Botulinum toxin B (Neurobloc) is a possible alternative.

Biomechanical Phenomena↗
PubMed2000

TatC is a specificity determinant for protein secretion via the twin-arginine translocation pathway.

The recent discovery of a ubiquitous translocation pathway, specifically required for proteins with a twin-arginine motif in their signal peptide, has focused interest on its membrane-bound components, one of which is known as TatC. Unlike most organisms of which the genome has been sequenced completely, the Gram-positive eubacterium Bacillus subtilis contains two tatC-like genes denoted tatCd and tatCy. The corresponding TatCd and TatCy proteins have the potential to be involved in the translocation of 27 proteins with putative twin-arginine signal peptides of which approximately 6-14 are likely to be secreted into the growth medium. Using a proteomic approach, we show that PhoD of B. subtilis, a phosphodiesterase belonging to a novel protein family of which all known members are synthesized with typical twin-arginine signal peptides, is secreted via the twin-arginine translocation pathway. Strikingly, TatCd is of major importance for the secretion of PhoD, whereas TatCy is not required for this process. Thus, TatC appears to be a specificity determinant for protein secretion via the Tat pathway. Based on our observations, we hypothesize that the TatC-determined pathway specificity is based on specific interactions between TatC-like proteins and other pathway components, such as TatA, of which three paralogues are present in B. subtilis.

Amino Acid Sequence↗
PubMed2000

Cyclin A down-regulation in TGFbeta1-arrested follicular lymphoma cells.

Transforming growth factor beta1 (TGFbeta1) induces growth arrest in many cell types, including B lymphocytes. We examined the effect of TGF on cell cycle progression of a non-Hodgkin lymphoma cell line of follicular lymphoma subtype (FL). After 48 h of TGFbeta1 (10 ng/ml) treatment, a significantly increased number of DoHH2 cells was retained in G(0)/G(1) phase. We examined the level of cell cycle components, cyclins, cyclin-dependent kinases (cdk), and their inhibitors. We found that the expression of cyclin A and p21(WAF1) molecules was primarily modulated by TGFbeta1 treatment while the expression of other regulatory components, like cyclins D, cyclin E, cdk2, cdk4, and cdk6 or p15(INK4B), p16(INK4A), and p27(KIP1) was not significantly affected. We further examined expression and activity of CREB/ATF family members to examine their roles in cyclin A inhibition. The binding activity of CREB-1 and ATF-2 to the CRE region of the cyclin A promoter was almost completely abolished due to the treatment. The total level of CREB-1, ATF-2, and ATF-3 was notably reduced. Moreover, CREB-1 was dephosphorylated due to the treatment as revealed by immunoblotting. We assume that down-regulation of cyclin A was mediated by the absence of CREB/ATF activation dimers. The profound effect on the ATF family of transcription factors indicates the complexity of TGFbeta1 action on FL B malignant cells.

Cell Cycle↗
PubMed2000

Somatosensory evoked potentials in progressive supranuclear palsy.

We report median and digital nerve somatosensory evoked potentials (SEPs) in 14 patients with probable progressive supranuclear palsy (PSP) along with transcortical long-loop reflexes, motor evoked potentials, and auditory startle responses. Enlarged cortical responses were found in 14 median and 13 digital nerve SEP studies, while long-loop reflexes were increased in only one patient. All motor evoked potential studies were normal. Auditory startle responses were either absent or reduced in 11 patients. The observed neurophysiological abnormalities may reflect cortical hyperexcitability but are distinct from those in other disorders associated with giant SEPs, such as progressive myoclonus epilepsy. A number of groups reported widespread cortical changes in addition to the characteristic subcortical neurofibrillary degeneration in post-mortem confirmed PSP. However, clinical features reflecting cortical dysfunction such as ideomotor apraxia and cortical sensory loss are uncommon in classical PSP. Furthermore, frontal lobe dementia which is frequently present in PSP patients, is thought to be of subcortical origin resulting from striato-frontal deafferentation. We propose that cortical neurofibrillary pathology may lead to subclinical intracortical disinhibition accounting for the enlarged cortical SEPs in PSP.

Aged↗
PubMed2000

Progression of Hoehn and Yahr stages in Parkinsonian disorders: a clinicopathologic study.

The progression to different Hoehn and Yahr (HY) stages was evaluated in 81 pathologically confirmed patients with parkinsonism. Patients with PD (n = 18) showed significantly longer latencies to each HY stage than patients with atypical parkinsonian disorder (APD). While no patient with PD developed a HY-III stage within 1 year of onset of motor symptoms, 72% of those with APDs did. In fact, development of a HY-III within 1 year of motor onset accurately predicted an APD. However, the progression to each HY stage was unhelpful in distinguishing the APDs from each other. Once patients with PD and APD became wheelchair-bound, both had equally short survival times.

Adult↗
PubMed2000

Adrenodoxin: structure, stability, and electron transfer properties.

Adrenodoxin is an iron-sulfur protein that belongs to the broad family of the [2Fe-2S]-type ferredoxins found in plants, animals and bacteria. Its primary function as a soluble electron carrier between the NADPH-dependent adrenodoxin reductase and several cytochromes P450 makes it an irreplaceable component of the steroid hormones biosynthesis in the adrenal mitochondria of vertebrates. This review intends to summarize current knowledge about structure, function, and biochemical behavior of this electron transferring protein. We discuss the recently solved first crystal structure of the vertebrate-type ferredoxin, the truncated adrenodoxin Adx(4-108), that offers the unique opportunity for better understanding of the structure-function relationships and stabilization of this protein, as well as of the molecular architecture of [2Fe-2S] ferredoxins in general. The aim of this review is also to discuss molecular requirements for the formation of the electron transfer complex. Essential comparison between bacterial putidaredoxin and mammalian adrenodoxin will be provided. These proteins have similar tertiary structure, but show remarkable specificity for interactions only with their own cognate cytochrome P450. The discussion will be largely centered on the protein-protein recognition and kinetics of adrenodoxin dependent reactions.

Adrenodoxin↗
PubMed2000

NMR solution structure of hPar14 reveals similarity to the peptidyl prolyl cis/trans isomerase domain of the mitotic regulator hPin1 but indicates a different functionality of the protein.

The 131-amino acid residue parvulin-like human peptidyl-prolyl cis/trans isomerase (PPIase) hPar14 was shown to exhibit sequence similarity to the regulator enzyme for cell cycle transitions human hPin1, but specificity for catalyzing pSer(Thr)-Pro cis/trans isomerizations was lacking. To determine the solution structure of hPar14 the (1)H, (13)C, and (15)N chemical shifts of this protein have been assigned using heteronuclear two and three-dimensional NMR experiments on unlabeled and uniformly (15)N/(13)C-labeled recombinant protein isolated from Escherichia coli cells that overexpress the protein. The chemical shift assignments were used to interpret the NOE data, which resulted in a total of 1042 NOE restraints. The NOE restraints were used along with 71 dihedral angle restraints and 38 hydrogen bonding restraints to produce 50 low-energy structures. The hPar14 folds into a betaalpha(3)betaalphabeta(2) structure, and contains an unstructured 35-amino acid basic tail N-terminal to the catalytic core that replaces the WW domain of hPin1 homologs. The three-dimensional structures of hPar14 and the PPIase domain of human hPin1 reveal a high degree of conservation. The root-mean-square deviations of the mean atomic coordinates of the heavy atoms of the backbone between residues 38 to 45, 50 to 58, 64 to 70, 81 to 86, 115 to 119 and 122 to 128 of hPar14 were 0.81(+/-0.07) A. The hPar14 model structure provides insight into how this class of PPIases may select preferential secondary catalytic sites, and also allows identification of a putative DNA-binding motif in parvulin-like PPIases.

Amino Acid Sequence↗
PubMed2000

dMi-2 and ISWI chromatin remodelling factors have distinct nucleosome binding and mobilization properties.

Mi-2 and ISWI, two members of the Snf2 superfamily of ATPases, reside in separate ATP-dependent chromatin remodelling complexes. These complexes differ in their biochemical properties and are believed to perform distinct functions in the cell. We have compared the remodelling activity of recombinant Drosophila Mi-2 (dMi-2) with that of recombinant ISWI. Both proteins are nucleosome-stimulated ATPases and promote nucleosome mobilization. However, dMi-2 and ISWI differ in their interaction with nucleosome core particles, in their substrate requirements and in the direction of nucleosome mobilization. We have used antibodies to immobilize a complex containing dMi-2 and the dRPD3 histone deacetylase from Drosophila embryo extracts. This complex shares the nucleosome-stimulated ATPase and nucleosome mobilization properties of recombinant dMi-2, demonstrating that these activities are maintained in a physiological context. Its functional properties distinguish dMi-2 from both SWI2/SNF2 and ISWI, defining a new family of ATP-dependent remodelling machines.

Adenosine Triphosphatases↗
PubMed2000

Unknown bisethylisooctanollactone isomers in industrial waste water. Isolation, identification and occurrence in surface water.

Unknown bisethylisooctanollactone isomers (BIOL isomers) which are chemical by-products of butyraldehyde synthesis, were isolated from industrial waste water applying various purification methods with subsequent semi-preparative high-performance liquid chromatography. Through interpretation of mass spectra after gas chromatographic separation the individual BIOL isomers were identified as stereoisomers of 2,4-diethyl-3-n-propyl-delta-valerolactone. Thus, it was possible for the first time to quantify the BIOL isomers in the river Rhine, Germany, with a mean sum concentration of 1.6 microg l(-1). A regular analysis performed over a period of almost two years of the river Rhine always gave the same ratio among the individual isomers. Drinking water production out of such water was studied, revealing that activated carbon filtration led to a 95% reduction of the BIOL concentration. Additional subsoil passage and a subsequent slowsand filtration led to a total elimination due to microbial degradation. Even if the BIOL isomers proved not to be relevant to drinking water, their behavior in the aquatic environment needs to be more thoroughly investigated since these compounds have been discharged for many years in high amounts into the river Rhine.

Calibration↗
PubMed2000

Copper(II) and copper(I) complexes with an open-chain N4 Schiff base ligand modeling CuZn superoxide dismutase: structural and spectroscopic characterization and kinetics of electron transfer.

The structure of the complex [CuII(PuPy)](ClO4)2 (PuPy = L = 1,8-bis(2-pyridyl)-2,7-diazaoctadiene-1,7) and the structure of the corresponding copper(I) complex were determined. In CuIIL(ClO4)2, a model compound with CuZnSOD activity, the unit CuIIL2+ has a tetrahedrally distorted square-planar N4 coordination geometry. The copper(I) complex with L was found to be dimeric, (CuIL)2(ClO4)2.DMF (DMF = N,N-dimethylformamide). The binuclear unit (CuIL)2(2+) has a helical structure with two ligands L bridging the two copper atoms to provide tetrahedral N4 coordination of each copper(I). In solutions of (CuIL)2(ClO4)2.DMF, solvent-dependent dissociation occurs according to D reversible 2M (D = (CuIL)2(2+); M = CuILSx+; S = solvent). Stopped-flow spectrophotometry was used to determine the rate constants for the dissociation of the dimer D (kM) and dimerization of the monomer M (kD) for S = acetonitrile and DMF. Equilibrium constants Kdim = kM/kD were determined spectrophotometrically. In aqueous solution, the oxidation of the dimer (CuIL)2(2+) by CoIII(NH3)5Cl2+ and cis- and trans-CoIII(en)2Cl2+ follows a second-order rate law, rate = kox[(CuIL)2(2+)][Co(III)]. Data for rate constant kox and for the activation parameters delta H++ and delta S++ are presented. In DMF, the oxidation of (CuIL)2(2+) by CoIII(NH3)5Cl2+ occurs via the monomer CuIL(DMF)x+ and the dissociation of (CuIL)2(2+) becomes rate-controlling. The reduction of CuIIL2+ by RuII(edta)H2O2- was found to be too fast to be resolved by stopped-flow spectrophotometry. The kinetic results are discussed mechanistically in terms of the redox switch aspects of the system.

Copper↗
PubMed2000

A new look at the microtubule binding patterns of dimeric kinesins.

The interactions of monomeric and dimeric kinesin and ncd constructs with microtubules have been investigated using cryo-electron microscopy (cryo-EM) and several biochemical methods. There is a good consensus on the structure of dimeric ncd when bound to a tubulin dimer showing one head attached directly to tubulin, and the second head tethered to the first. However, the 3D maps of dimeric kinesin motor domains are still quite controversial and leave room for different interpretations. Here we reinvestigated the microtubule binding patterns of dimeric kinesins by cryo-EM and digital 3D reconstruction under different nucleotide conditions and different motor:tubulin ratios, and determined the molecular mass of motor-tubulin complexes by STEM. Both methods revealed complementary results. We found that the ratio of bound kinesin motor-heads to alphabeta-tubulin dimers was never reaching above 1.5 irrespective of the initial mixing ratios. It appears that each kinesin dimer occupies two microtubule-binding sites, provided that there is a free one nearby. Thus the appearances of different image reconstructions can be explained by non-specific excess binding of motor heads. Consequently, the use of different apparent density distributions for docking the X-ray structures onto the microtubule surface leads to different and mutually exclusive models. We propose that in conditions of stoichiometric binding the two heads of a kinesin dimer separate and bind to different tubulin subunits. This is in contrast to ncd where the two heads remain tightly attached on the microtubule surface. Using dimeric kinesin molecules crosslinked in their neck domain we also found that they stabilize protofilaments axially, but not laterally, which is a strong indication that the two heads of the dimers bind along one protofilament, rather than laterally bridging two protofilaments. A molecular walking model based on these results summarizes our conclusions and illustrates the implications of symmetry for such models.

Adenosine Triphosphate↗
PubMed2000

Transcriptional control: The benefits of selective insulation.

In eukaryotes, cis-regulatory sequences are often a long way away from the transcription start site, and interactions between regulatory elements can be blocked by 'insulator' sequences. A novel type of cis-regulatory element has now been found that selectively permits some interactions across insulators.

Animals↗
PubMed2000

Immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) frequently is a progressive disease without causative therapy options. Following the hypothesis that in certain patients autoantibodies against cardiac structures may induce, maintain, or promote the progression of the disease, we investigated whether the elimination of these autoantibodies through immunoadsorption would improve cardiac function. METHODS AND RESULTS: This prospective case-control study included 34 patients with IDC. Each patient presented with moderate to severe heart failure and evidence of autoantibodies directed against beta(1)-adrenoceptors (beta(1)-AABs). Seventeen patients received standard medical therapy (control group), whereas 17 were also treated with immunoadsorption (treatment group) to eliminate beta(1)-AABs. A 1-year follow-up included echocardiographic assessment of left ventricular ejection fraction and internal diameters, beta(1)-AAB levels, and clinical status every 3 months. Within 1 year, the mean+/-SD left ventricular ejection fraction rose from 22.3+/-3.3% to 37.9+/-7.9% (P=0.0001) in the treatment group, with a relative increase of 69.9%. However, in the control group, no overall increase was seen (from 23.8+/-3.0% to 25.2+/-5.9%, P=0. 3154). Left ventricular diameter in diastole decreased by 14.5% from 74.5+/-7.1 to 63.7+/-6.0 mm in the treatment group (P=0.0001) and by 3.8% (P=0.2342) in the control group. In the treatment group, the NYHA functional rating improved after immunoadsorption (P=0.0001). beta(1)-AABs did not increase anew. CONCLUSIONS: In IDC, the use of immunoadsorption is superior to the use of standard medical therapy. It significantly improves cardiac performance and clinical status.

Autoantibodies↗
PubMed2000

Cryopreservation of semen from pubertal boys with cancer.

BACKGROUND: The possibility of cryopreservation of semen from adolescents has until now received only little attention. Therefore, we have investigated the possibility of cryopreservation of semen in adolescent boys with cancer. PROCEDURE: Forty-five boys, aged 13-18 years, admitted because of cancer during the period January 1, 1995 to July 31, 1998 were eligible. Semen was obtained after masturbation in the majority of the cases. In three boys, semen was preserved after penile vibration or electroejaculation in general anaesthesia. The semen samples were analysed for concentration, motility, and morphology according to the WHO guidelines. The sample was transferred into straws prior to cryopreservation at 196 degrees C in liquid nitrogen. RESULTS: Twenty-one boys delivered a semen sample for cryopreservation. Four boys were offered and accepted sperm banking but were not able to produce a sample. In 20 cases time did not allow an attempt of sperm banking, the boy was not assessed to be mature enough to deliver a semen sample, or the procedure was not accepted. The boys delivered 1-3 samples, and the total number of spermatozoa ranged from 0-210 millions. Median percentage of motile sperm was 50% (range 9-86%). Semen quality improved with age; however, a 13- year- old boy produced 75 million spermatozoa with 38% motile cells. CONCLUSIONS: Pubertal maturation should be assessed in all boys admitted for cancer, and the possibility of sperm banking should be discussed with the patient and his parents.

Adolescent↗
PubMed2000

Urokinase receptor up-regulation in head and neck squamous cell carcinoma.

BACKGROUND: Urokinase-type plasminogen activator is important for matrix degradation and motility of cancer cells. For effective invasion, urokinase has to be associated with its cell surface receptor.(1) METHODS: We analyzed 33 head and neck squamous cell carcinomas (hnSCC) and 14 mucosal tissue samples for the expression of urokinase receptor using Northern hybridization and correlated expression levels to clinical and histopathologic data. Urokinase expression was determined by fibrin zymography. RESULTS: The expression of urokinase receptor is significantly increased in hnSCC compared with adjacent mucosa. Expression levels in primary tumors show no statistically significant correlations to T staging, metastasis, recurrence, or differentiation stage of the resected tumors. Furthermore, there was no correlation between urokinase and urokinase receptor expression levels in SCC samples. CONCLUSIONS: Urokinase receptor expression is increased in hnSCC, but it is not useful as a prognostic marker for the metastatic behavior of primary tumors. Comparison of our data with previously published reports is discussed.

Adult↗