Search PubMed⌕ Search

Biomedical subjects

A Müller

Publications and source records attributed to A Müller.

At least 289 records · Page 16Linked to original sources
PubMed1997

Collagen crosslinks in fibromyalgia.

OBJECTIVE: To determine if abnormal collagen metabolism is a characteristic of fibromyalgia. METHODS: The diagnosis of fibromyalgia was made according to the American College of Rheumatology criteria. Skin biopsy samples were obtained from the trapezius region of 8 patients with fibromyalgia. Urine was collected under standardized conditions from 55 control subjects and 39 patients with fibromyalgia, and serum was obtained from 17 controls and 22 patients with fibromyalgia. Pyridinoline (Pyd), an indicator of connective tissue disease, and deoxypyridinoline (Dpyd), an indicator of bone degradation, both of which represent products of lysyl oxidase-mediated crosslinking in collagen, were analyzed by ion-paired and gradient high-performance liquid chromatography (HPLC) methods with fluorescence detection. Levels of hydroxyproline (Hyp), a collagen turnover marker, were also measured. The findings were related to creatinine levels, and the Pyd:Dpyd ratio was determined. RESULTS: Highly ordered cuffs of collagen were observed around the terminal nerve fibers by electron microscopic examination of biopsy tissue from all 8 patients with fibromyalgia, but were not observed in any of the control skin samples. The Pyd:Dpyd ratios in the urine and serum and the Hyp levels in the urine were significantly lower in patients with fibromyalgia than in healthy controls. CONCLUSION: Decreased levels of collagen crosslinking in fibromyalgia may contribute to remodeling of the extracellular matrix and collagen deposition around the nerve fibers, and may contribute to the lower pain threshold at the tender points. Analysis of altered collagen metabolism either by histologic examination on biopsy, or preferably, by HPLC analysis of collagen metabolites in urine or serum may aid in understanding more about the pathogenesis of fibromyalgia.

Amino Acids↗
PubMed1997

The active site histidines of creatine kinase. A critical role of His 61 situated on a flexible loop.

A histidine residue with a pKa of 7 has been inferred to act as a general acid-base catalyst for the reaction of creatine kinase (CK), catalyzing the reversible phosphorylation of creatine by ATP. The chicken sarcomeric muscle mitochondrial isoenzyme Mib-CK contains several histidine residues that are conserved throughout the family of creatine kinases. By X-ray crystal structure analysis, three of them (His 61, His 92, and His 186) were recently shown to be located close to the active site of the enzyme. These residues were exchanged against alanine or aspartate by in vitro mutagenesis, and the six mutant proteins were expressed in E. coli and purified. Structural integrity of the mutant proteins was checked by small-angle X-ray scattering. Kinetic analysis showed the mutant His 61 Asp to be completely inactive in the direction of ATP consumption while exhibiting a residual activity of 1.7% of the wild-type (wt) activity in the reverse direction. The respective His to Ala mutant of residue 61 showed approximately 1% wt activity in the forward and 10% wt activity in the reverse reaction. All other mutants showed near wt activities. Changes in the kinetic parameters K(m) or Vmax, as well as a significant loss of synergism in substrate binding, could be observed with all active mutants. These effects were most pronounced for the binding of creatine and phosphocreatine, whereas ATP or ADP binding were less severely affected. Based on our results, we assume that His 92 and His 186 are involved in the binding of creatine and ATP in the active site, whereas His 61 is of importance for the catalytic reaction but does not serve as an acid-base catalyst in the transphosphorylation of creatine and ATP. In addition, our data support the idea that the flexible loop bearing His 61 is able to move towards the active site and to participate in catalysis.

Animals↗
PubMed1997

The determination of pyridinium crosslinks in urine and serum as a possible marker of cartilage degradation in rheumatoid arthritis.

The determination of the collagen crosslinks pyridinoline (Pyd) and deoxypyridinoline (Dpyd) seems to be a successful way of characterizing topic destructive processes in rheumatoid arthritis (RA). Dpyd is a specific marker of collagen I resorption in bone, whereas Pyd is released from types I and II collagen in bone and cartilage. Both crosslinks were examined in 38 RA patients concurrently by RP-gradient-HPLC in urine and serum. A positive correlation was found between the inflammatory activity (measured by CrP) and the level of collagen crosslinks in urine. A correlation between serum and urine concentrations was demonstrable for Pyd, but not for Dpyd. Different elimination kinetics for fragments containing either Pyd or Dpyd are a possible explanation for this observation. The ratio of Pyd/Dpyd is known to be a useful marker to distinguish between destruction of cartilage and bone collagen. Because the Pyd/Dpyd ratio in urine does not necessarily correspond to that in serum, probably as a result of metabolic or elimination processes, the usefulness of the relationship between the crosslinks in urine as a method of differentiating between cartilage and bone degradation must be questioned.

Adult↗
PubMed1997

[Basaliomas with invasion of bone: problems and prognosis].

The cure rate for basal cell carcinomas with the appropriate surgical management is excellent. However, when bony involvement is present the prognosis is adversely effected. Only 0.5% of orofacial basal cell carcinomas in our series had bony involvement. These 12 cases were analysed for recurrence rate. This revealed rates from 60% with primary tumours to 90% for recurrences. According to Kaplan-Meier the expected recurrence rate within 10 years is about 90%. Surprisingly the crucial factor mitigating against a cure is the presence of tumour bony infiltration, rather than the demonstration of tumour at the resection margins.

Adult↗
PubMed1997

Actions of the antiarrhythmic peptide AAP10 on intercellular coupling.

Disturbances in gap junction distribution and a decrease in the connexin43 content of the heart were shown to occur after myocardial infarction and in ischemic heart disease, respectively. These changes are now thought to play an important role in the genesis of arrhythmias associated with these diseases. It is thought that agents that can increase cellular coupling might be beneficial in these situations. Recently, we presented data showing that the synthetic peptide AAP10 acts antiarrhythmically in a model of regional ischemia. The data suggested that AAP10 might act via an increase in cellular coupling. The goal of this study was to establish whether AAP10 can interact with cardiac gap junctions. Measurements of the stimulus-response-interval (SRI) in guinea pig papillary muscle showed that high concentrations of AAP10 (1 microM) can decrease the SRI by about 10% under normoxic conditions. At lower concentrations (10 nM) AAP10 had no effect on SRI under normoxic conditions but prevented the increase in the SRI induced by perfusion with hypoxic, glucose-free Tyrode's solution. Double-cell voltage-clamp experiments confirmed that AAP10 can interact with cardiac gap junctions. 10 nM AAP10 could either diminish or reverse the run-down of gap junction conductance normally observed in pairs of guinea pig ventricular myocytes. During control gap junction conductance decreased with a rate of -2.5 +/- 2.0 nS/min. After application of 10 nM AAP10 gap junction conductance increased with a rate of +1.0 +/- 0.7 nS/min (p < 0.01). After washout of AAP10 gap junction conductance decreased again with a rate not significantly different from control. Our results show that AAP10 does interact with gap junctions. Because no other effects of AAP10 on other electrophysiological parameters could be found, this action on gap junctions might be the basis of AAP10's antiarrhythmic effect seen in previous studies.

Action Potentials↗
PubMed1997

[Computer tomographic diagnosis of acute cerebral ischemmia].

Computed tomography (CT) is the first step in the radiological diagnostics of brain emergencies. We intend to study which pathophysiological changes are detected by CT and how CT contributes to prognosis and patient management in acute cerebral ischemia. We review recent publications about the role of CT in acute cerebral ischemia. Ischemic brain edema is associated with a decreased X-ray attenuation. Computed tomography is thus highly sensitive in detecting irreversibly damaged ischemic brain tissue. Patients showing large volumes of ischemic edema, exceeding one third of the middle cerebral artery territory, do not benefit from thrombolysis and have an increased risk of brain hemorrhage. The brain territory at risk from ischemia can be detected by CT angiography. To combine CT with CT angiography is a pragmatic approach which enables carefully directed treatment in acute cerebral ischemia.

Acute Disease↗
PubMed1997

[Acute Borrelia infection. Unilateral papillitis as isolated clinical manifestation].

BACKGROUND: Borrelia burgdorferi is the cause of erythema chronicum migrans and Lyme disease. Ticks like Ixodes ricinus are responsible for transmission. Frequently, the tick bite is not noticed by the patient. Eye manifestations, such as keratoconjunctivitis, scleritis, chronic uveitis, vitritis, chorioretinitis, optic nerve disease, orbital myositis and paresis of the eye muscles, often occur after a long period of time and vary greatly. PATIENTS AND METHODS: We present below the case reports of a man 38 years old and a woman of 31, each with manifestation of an ocular Borrelia infection (papillitis and panuveitis, respectively). RESULTS: By antibody-screening with the ELISA technique and Western Blot analysis we were able to prove the serological infection. After specific antibiotic therapy, ocular inflammation improved rapidly, as did visual acuity. The papillitis only healed partially. CONCLUSIONS: In case of therapy-resistant inflammation of the eye we have to exclude general infections because cortisone therapy alone may result in worsening the condition. VECP can be used effectively in the differential diagnosis of papilloedemas. Early diagnosis and therapy of an acute Borrelia infection restrict the extent of the lesions and prevent ocular and general late manifestations. Seronegative values in subjects strongly suspected of having Lyme disease do not necessarily exclude the diagnosis of Lyme disease.

Borrelia burgdorferi Group↗
PubMed1997

Cost-minimal immunization in the Greenwood epidemic model.

In the present paper, we extend the investigations of Lefèvre [1] and Dayananda and Hogarth [2] to a model with a more realistic economical setting and with a more flexible transition mechanism for the population. The new aspects include terminal costs, a stopping opportunity, discounting, and a scheme for generating a wealth of specific probability distributions, not only for the immunization step, but also for the infection step. In the second part of the paper, we also include fixed costs. While showing that our model without fixed costs has essentially the same simple solution as the model by Lefèvre [1] and Dayananda and Hogarth [2], the largest part of the paper deals with new structural properties such as an asymptotic behavior for large horizon and concavity of the minimal cost functions. The solutions in the model with and without fixed costs differ considerably. The main tool of our investigation is the theory of Markovian decision processes.

Costs and Cost Analysis↗
PubMed1997

The auditory-vibratory system of the bushcricket Polysarcus denticauda (Phaneropterinae, Tettigoniidae). I. Morphology of the complex tibial organs.

The structure of the complex tibial organs in the fore-, mid- and hindlegs of the bushcricket Polysarcus denticauda (Tettigoniidae, Phaneropterinae) is described comparatively. As is common for bushcrickets, in each leg the tibial organs consist of the subgenual and intermediate organs and the crista acustica. Only in the forelegs are sound-transmitting structures present. They consist of the spiracle, acoustic trachea, and two tympana; the latter are not protected by tympanal covers. The tympana in P. denticauda are extremely thick, not only bordering the two tracheal branches to the outside but also forming the outer wall of the hemolymph channel. The morphology of the tracheae in the mid- and hindlegs is significantly different, causing structural differences, especially in dimensions of the hemolymph channel. The number of scolopidia of the crista acustica of the foreleg is extremely high for a bushcricket. Approximately 50 receptor cells were found, about half of them being located in the distal quarter of the long axis of this organ. Some of the receptors are positioned in parallel on the dorsal wall of the anterior tracheal branch. The number, morphology and dimensions of the scolopidia within the crista acustica of the mid- and hindlegs differ significantly from those of the forelegs, decreasing in both legs to eight and seven receptor cells, respectively. Although the dimensions of the subgenual and intermediate organs are considerably larger in the mid- and hindlegs, the number of receptor cells is approximately the same in the different legs, being somewhat higher in both receptor organs than in those of many other bushcricket species studied previously.

Acoustic Stimulation↗
PubMed1997

Histological and biochemical changes induced by total bile duct ligation in the rat.

The aim of the present investigation was to assess in a correlated biochemical and morphological study the dynamics of fibrogenesis after bile duct ligation and to compare the time course of alterations with those occurring in thioacetamide induced liver fibrosis. The data show that, after bile duct obstruction, the deposition of connective tissue elements and formation of ductular proliferates rapidly set in. The index of fibroplasia correlated well with the changes of the OH-proline concentration of the liver. Comparing the biliary fibrosis with the thioacetamide induced liver fibrosis, the progress of the former occurred more rapidly, even though in both cases only a few necroses were observed. Therefore, we suggest that in biliary fibrosis other mechanisms are responsible for the rapid onset of production of extracellular material and proliferative processes than in thioacetamide-induced liver fibrosis.

Alanine Transaminase↗
PubMed1997

Expand Long PCR for fragile X mutation detection.

Fragile X mutation detection by DNA analysis enables accurate diagnosis of the fragile X syndrome. The mutation involves the expansion of CGG repeats in the FMR1 gene and has been primarily detected by the Southern blotting method. In this study we present a novel, efficient and reliable PCR protocol that is more convenient for routine diagnosis of the fragile X syndrome. This method is based on the use of the Expand Long PCR System, which enables the amplification of normal, premutated and full-mutated alleles, and therefore provides complete CGG repeat analysis of the FMR1 gene. Normal alleles were easily detected by ethidium bromide staining of the agarose gels, suggesting that this assay could be used as a screening test for a large number of referrals. The amplified premutations and full mutations were identified by hybridization with a digoxigenin-labeled 5'-(CGG)5-3' probe, followed by chemiluminescent detection. The accuracy of our Expand Long PCR protocol was confirmed by Southern blot analysis, illustrating that the Expand Long PCR results concur with those of Southern blotting. In this paper we propose a new strategy for molecular diagnosis of the fragile X syndrome in which our Expand Long PCR assay is used as the first screening test for fragile X mutation detection.

Alleles↗
PubMed1997

Complement factor C3 deposition and serum resistance in isogenic capsule and lipooligosaccharide sialic acid mutants of serogroup B Neisseria meningitidis.

Serogroup B meningococci express sialic acids on their surfaces as a modification of the lipooligosaccharide (LOS) and as capsular material consisting of alpha2,8-linked sialic acid homopolymers. The aim of this study was to elucidate the impact of each sialic acid component on the deposition of complement factor C3 and serum resistance. For this purpose, we used isogenic mutants deficient in capsule expression (a polysialyltransferase mutant) or sialylation of the LOS (a galE mutant) or both (a mutant with a deletion of the cps gene locus). Bactericidal assays using 40% normal human serum (NHS) demonstrated that both the capsule and LOS sialic acid are indispensable for serum resistance. By immunoblotting with monoclonal antibody MAb755 that is specific for the C3 alpha-chain, we were able to demonstrate that C3 from 40% NHS was covalently linked to the surface structures of meningococci as C3b and iC3b, irrespective of the surface sialic acid compounds. However, C3b linkage was more pronounced and occurred on a larger number of target molecules in galE mutants with nonsialylated LOS than in meningococci with wild-type LOS, irrespective of the capsule phenotype. C3b deposition was caused by both the classical pathway (CP) and the alternative pathway of complement activation. Use of 10% NHS revealed that at low serum concentrations, C3 deposition occurred via the CP and was detected primarily on nonsialylated-LOS galE mutants, irrespective of the capsular phenotype. Accordingly, immunoglobulin M (IgM) binding to meningococci from heat-inactivated NHS was demonstrated only in both encapsulated and unencapsulated galE mutants. In contrast, inhibition of IgA binding required both encapsulation and LOS sialylation. We conclude that serum resistance in wild-type serogroup B meningococci can only be partly explained by an alteration of the C3b linkage pattern, which seems to depend primarily on the presence of wild-type LOS, since a serum-resistant phenotype also requires capsule expression.

Bacterial Capsules↗
PubMed1997

Pancreatic autoantibodies in Crohn's disease: a family study.

BACKGROUND: Pancreatic antibodies occur in about one third of patients with Crohn's disease. AIMS: To evaluate the relevance of pancreatic antibodies as a genetic marker in patients with Crohn's disease and their first degree family members and spouses. To characterise further pancreatic antibodies by assessment of IgG subclasses. METHODS: Six hundred and fifty serum samples were tested for pancreatic antibodies by immunofluorescence on sections of human pancreas. Incidence of pancreatic antibodies and their subtypes were studied on 212 serum samples from patients with Crohn's disease. In the familial study, 72 patients with Crohn's disease and 196 first degree family members and 26 patients with ulcerative colitis and 90 first degree family members were included. Ten healthy families served as controls. RESULTS: Pancreatic antibodies were found in 58 (27%) of the patients with Crohn's disease and in none of the controls. Thirty patients had pancreatic antibodies of subtype I characterised by a drop-like fluorescence in the pancreatic acini, 28 patients had subtype II with a fine speckled staining in the acinar cells. Pancreatic antibodies of subtype I were both IgG1 and IgG2 antibodies by contrast with subtype II which were mainly of IgG1 subclass. Only five of 196 first degree relatives of patients with Crohn's disease had pancreatic antibodies. Four of these people had anamnestic data compatible with inflammatory bowel disease. Further investigations showed Crohn's disease in two of these people. In families with more than one member positive for pancreatic antibodies, pancreatic antibodies were of the same subtype in all cases. CONCLUSIONS: Pancreatic antibodies are a specific marker for Crohn's disease. Two subgroups of pancreatic antibodies can be distinguished by their pattern and immunoglobulin subclasses. Pancreatic antibodies rarely occur in family members of patients with Crohn's disease. These family members may also have Crohn's disease.

Autoantibodies↗
PubMed1997

Effect of macrophage stimulation on collagen biosynthesis in the healing wound.

Immunomodulators that enhance macrophage function have been shown to be beneficial in a number of wound-healing models in humans and in experimental animals. The exact mechanism of this improved healing is unclear. To assess the role of collagen biosynthesis, the immunomodulator glucan phosphate was utilized in two murine models of wound healing, i.e., colon anastomosis and full-thickness skin incision. Tensile strength was evaluated using computer-assisted constant velocity tensiometry. Collagen biosynthesis was determined by assaying hydroxyproline content of wound hydrolysates by N-(9-fluorenyl)methoxycarbonyl/o-phthalaldehyde high-performance liquid chromatography. Experimental animals were treated with (1-3)-beta-D-glucan phosphate (250 mg/kg) intravenously 24 hours prior to colon anastomosis or skin incision. A second dose of glucan phosphate was given immediately postoperatively. Control animals received dextrose and water (5% w/v) intravenously. Tensile strength and hydroxyproline content were measured on postoperative Day 3. In the skin wound model, glucan phosphate treatment increased (P < 0.05) tensile strength by 42 per cent (342.5 +/- 12.2 vs 241.8 +/- 4.8 g), and hydroxyproline content was increased by 23.5 per cent (242.0 +/- 14.4 vs 196.8 +/- 10.5 pmol/microg; P < 0.05). In the glucan phosphate group, colon tensile strength was significantly (P < 0.05) increased by 34 per cent (34.2 +/- 2.3 g vs 45.8 +/- 2.1 g), and hydroxyproline content was increased by 7 per cent (47.45 +/- 3.31 vs 44.34 +/- 3.74 pmol/microg). These data indicate that macrophage modulation with glucan phosphate will increase tensile strength in experimental colon and skin wounds. In addition, we observed a positive correlation between glucan phosphate treatment, wound tensile strength, and collagen biosynthesis.

Adjuvants, Immunologic↗
PubMed1997

[Von Willebrand factor concentrations in blood plasma of Bernese mountain dogs].

Many Bernese Mountain dogs have been found to exhibit an increased hemorrhagic tendency of unknown etiology. Since other bleeding disorders have been excluded by routine tests and Bernese Mountain dogs have been listed to have von Willebrand's disease (vWD), we analyzed the plasma concentration of the von Willebrand Factor (vWF) in 160 Bernese Mountain dogs that were used for breeding in Switzerland in 1992. We also evaluated the suitability of the commercial Asserachrom vWF test kit to quantitate vWF in canine plasma by comparing the plasma vWF determination with validated vWF ELISA test. The vWF plasma concentration in Bernese Mountain dogs ranged from 13% to 162%, with the Asserachrom test kit (normal range 67% to 124%). Similar values were obtained with the research vWF ELISA kit (10% to 166%), and there was a close correlation between the two test methods. In 8 of the 9 Bernese Mountain dogs with initially low vWF concentration (< 60%), the determination was repeated on another sample. Since the values were well within the normal range, a problem with the collection of blood for the first determination is suspected. We conclude that vWD does not appear to be a clinical issue in Bernese Mountain dogs in Switzerland and is, therefore, not likely to be the cause of the observed bleeding tendency. The commercially available Asserachrom vWF test kit seems suitable for the determination of canine vWF plasma concentrations. It is recommended that low vWF values will be confirmed by the determination in second samples.

Animals↗
PubMed1997

Preparation and crystallization of a cross-linked complex of bovine adrenodoxin and adrenodoxin reductase.

Bovine adrenodoxin was cross-linked to adrenodoxin reductase with 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide. Mass spectrometry showed the reaction product to be a 1:1 complex of the two proteins with M(r) = 64,790 +/- 50. The cross-linked complex showed cytochrome c reductase activity and could be crystallized by hanging-drop vapor diffusion. Crystals of the adrenodoxin-adrenodoxin reductase complex are hexagonal, space group P6(1)22 or P6(5)22, with a = 93.26 A and c = 612.20 A and diffract to 2.9 A resolution at 100 K. Assuming two cross-linked complexes per asymmetric unit yields a reasonable V(M) of 2.97 A3/Da.

Adrenodoxin↗
PubMed1997

[CT-angiography for diagnostic assessment of intracranial vascular aneurysms].

Intracranial aneurysms bear a high risk of morbidity and mortality especially when they have become symptomatic due to rupture or represent a space occupying lesion. Therefore operative treatment is aimed at the obliteration of the aneurysm to eliminate the risk of hemorrhage. Planning of treatment requires a diagnostic resolution capable of showing aneurysms and their anatomic relationship to the adjacent structures. Due to technical advances computed tomography has reached a diagnostic accuracy sufficient to plan aneurysm treatment. This report describes the present state of three-dimensional spiral-CT angiography (3D-spiral-CTA) and our protocol to examine the arteries of the Circle of Willis for the presence and microanatomy of aneurysms. The experience of 46 patients with 64 aneurysms is reported and the diagnostic value of the method in comparison to conventional angiography is evaluated.

Aneurysm, Ruptured↗