[Intersectoral patient care in rheumatology: concept and preliminary experiences with a model project]. / Sektorenübergreifende Versorgung in der Rheumatologie: Konzept und erste Erfahrungen in einem Modellprojekt.

In October 2006 the Rheumaklinik Ostbayern was founded as a clinic for acute rheumatology patient care, carried by Landkreis Passau Krankenhaus GmbH. The clinic operates in close professional cooperation with the Orthopädiezentrum Bad Füssing, an adjacent rehabilitation clinic carried by Deutsche Rentenversicherung Bayern Süd. The close constructional and personnel network between the two institutions creates optimal conditions for an interdisciplinary and intersectoral approach. The authors report their first experiences since foundation of the clinic and completion of a cooperation contract.

[Outcome measurement in musculoskeletal diseases: recommendation for a core set of scales for use in rehabilitation]. / Outcome-Messung bei muskuloskelettalen Krankheiten: Vorschlag für ein Core-Set von Instrumenten zum Einsatz in der Rehabilitation.

By application of a standardized core set of outcome measurement instruments, comparison between studies as well as meta-analyses in rehabilitation research can be facilitated. The German Society for Rheumatology has commissioned its working group on rehabilitation with the development of a proposal for such a core set of outcome measurement instruments. In a first step, dimensions for outcome measurement in rehabilitation were defined by a group of experts which represented rehabilitation hospitals, acute care hospitals, and research groups specialized in outcome measurement. The Delphi method was used in a multiple step consensus process. In a second step, instruments and procedures to operationalize the relevant dimensions were chosen. Reliability, validity, sensitivity to change, and practicability were used as criteria for selecting measurement instruments. The main intention of the proposed core set of outcome measurement instruments is to facilitate the processes of planning and carrying out rehabilitation research studies. Furthermore, the proposed instruments can be used for clinical documentation systems as well as for internal or external quality assurance programs.

[Conservative nonpharmacological treatment of arthrosis]. / Nichtmedikamentöse konservative Therapie der Arthrose.

There are different options for nonpharmacological therapies in osteoarthritis. An educational program and instruction of the patient are of major importance. There is evidence that manual physical therapy and exercise improve function and reduce pain in osteoarthritic joints. Thermal modalities are employed for short-term pain relief and change the intra-articular temperature. Electrotherapy, ultrasound, balneotherapy, and acupuncture show positive therapeutic effects. Orthotics, braces, and wedged insoles may be beneficial in selected cases. Based on the present findings, further investigations are needed to prove the effectiveness of various methods in physical therapy and nonpharmacological approaches to the management of osteoarthritis.

Bivalency and epitope specificity of a high-affinity IgG3 monoclonal antibody to the Streptococcus group A carbohydrate antigen. Molecular modeling of a Fv fragment.

The binding of Strep 9, a mouse monoclonal antibody (mAb) of the IgG3 subclass directed against the cell-wall polysaccharide of Group A Streptococcus (GAS), has been characterized. The intact antibody and proteolytic fragments of Strep 9 bind differently to GAS: the intact mAb and F(ab)2' have greater affinity for the carbohydrate epitope than the monomeric Fab or F(ab)'. A mode of binding in which Strep 9 binds bivalently to portions of the polysaccharide on adjacent chains on GAS is proposed. A competitive ELISA protocol using a panel of carbohydrate inhibitors shows that the branched trisaccharide, beta-D-GlcpNAc-(1-->3)-[alpha-L-Rhap-(1-->2)]-alpha-L-Rhap, and an extended surface are key components of the epitope recognized by Strep 9. Microcalorimetry measurements with the mAb and two synthetic haptens, a tetrasaccharide and a hexasaccharide, show enthalpy-entropy compensation as seen in other oligosaccharide-protein interactions. Molecular modeling of the antibody variable region by homology modeling techniques indicates a groove-shaped combining site that can readily accommodate extended surfaces. Visual docking of an oligosaccharide corresponding to the cell-wall polysaccharide into the site provides a putative model for the complex, in which a heptasaccharide unit occupies the site and the GlcpNAc residues of two adjacent branched trisaccharide units occupy binding pockets within the groove-shaped binding site.

Cartilage thickness measurement in magnetic resonance imaging.

To assess the accuracy of cartilage thickness measurements in magnetic resonance imaging (MRI), we compared data obtained by cartilage thickness measurements in MRI with corresponding histological sections of 14 human proximal tibial articular surfaces. Each proximal tibial articular surface was cut into five medial and lateral slices and each of these slices was divided into three sectors providing 420 sectors, 406 of which were evaluated in our study. The overall correlation coefficient (r) was 0.96. Topographical differences were found. The lowest correlation coefficient in our series was observed in the anterior part of the medial tibial plateau (r = 0.88). Cartilage thickness measurements in MRI were more accurate in cartilage thicker than 2 mm (r = 0.94) than in thinner cartilage layers (r = 0.73). There were no significant differences in cartilage thickness measurements in different grades of osteoarthritis. However, the mean percentage difference between cartilage thickness in MRI and histology was about 10% in our series.

Purification and characterization of the Cu,Zn SOD from Escherichia coli.

The periplasmic Cu,Zn superoxide dismutase has been purified to homogeneity by a procedure, which depended upon osmotic shock followed by two chromatographic columns. Its subunit weight, determined by electrospray ionization mass spectrometry, was found to be 15,737 +/- 1.6. The second derivative ultraviolet spectrum indicated a lack of tryptophan. The amino acid composition as well as a partial N-terminal amino acid sequence is reported. The specific activity was 3700 U/mg and the corresponding copper content was 0.77 atoms Cu/subunit. The enzyme was quite unstable and overnight dialysis against EDTA or even prolonged dialysis against neutral phosphate buffer caused partial loss of activity and of copper and visible precipitation. It is likely that some losses occurred during the isolation procedure, and if these could have been prevented the copper content would have been 1.0 Cu/subunit and the specific activity would have been 4800 U/mg. It now appears likely that gram negative bacteria will commonly be found to contain a periplasmic Cu,Zn SOD.

Lesions of the alar ligaments. In vivo and in vitro studies with magnetic resonance imaging.

STUDY DESIGN: This study analyzed anatomic characteristics of the alar ligaments and the possibility of imaging them with magnetic resonance imaging. Also determined was whether artificial ruptures of the alar ligament can be recognized experimentally. OBJECTIVE: To determine the ability of magnetic resonance imaging to visualize normal, torn, resected alar ligaments. SUMMARY OF BACKGROUND DATA: There are no studies about computed tomography or magnetic resonance imaging findings of alar ligaments and after anatomic sections. Direct visualization of the complete ligament is not possible for computed tomography. No precise diagnostic method for showing a ruptured alar ligaments has been described. Magnetic resonance imaging seems to be the method of choice for distinguishing between normal and pathologic soft tissue. METHODS: Fifteen specimens from accident victims underwent anatomic dissection. In addition, ligaments from three groups were examined: 1) eight volunteers, 2) seven patients, and 3) 17 fresh cadaveric specimen before anatomic exploratory dissection. In seven of these specimens, one ligament was cut to simulate an artificial disruption and magnetic resonance imaging was repeated. RESULTS: Lesions of the alar ligaments were found in four of 15 prepared specimens. Using magnetic resonance imaging, the alar ligaments could be identified in all volunteers, patients, and specimen except one. No ruptures were found in the 17 specimens. Of the seven resected specimens, all cuts could be demonstrated by magnetic resonance imaging. CONCLUSION: Magnetic resonance imaging is useful for showing lesions of the alar ligaments because of a high soft tissue contrast, plane independence imaging, possibility of functional scans, and secondary reconstruction from three-dimensional data sets.

[Comparative histomorphometry of subchondral bone density and articular cartilage thickness in the tibial head in early human arthritis]. / Vergleichende Histomorphometrie der subchondralen Knochendichte und Gelenkknorpeldicke im Tibiakopf bei humanen Früharthrosen.

The articular cartilage thickness and subchondral bone density of 50 human tibial heads were histomorphometrically measured by an image analysing system and topographically examined in relation to age, sex and grade of osteoarthrosis (OA). Altogether we evaluated 12,000 items. Independent of OA the lateral tibial plateau shows a significant thicker cartilage layer than the medial. In central joint areas we find a thicker cartilage cover than in marginal. Corresponding to the literature cartilage fibrillation according to OA grade 1 and 2 (Otte 1969, Fassbender 1975) accumulates in the lateral and dorsal tibial head including the meniscus covered area. The cartilage thickness decreases with age independent of OA. Without major alterations of the topographical pattern the cartilage thickness however shows a significant increase in early OA (grade 1). For that reason measurements of the cartilage thickness and joint space narrowing are not appropriate for defining early OA. The subchondral bone density shows high values ventromedially and dorsolaterally independent of sex, age or OA. Beneath central joint areas higher values are found than marginally. Corresponding to the topical literature our results point at the model of the real loaded knee joint, which says that the mean loading forces do not act on the middle of the joint but on the medial plateau. The dorsolateral density centre could be an expression of the functional adaptation of the bended knee joint. In joint areas with cartilage fibrillation (OA grade 1) we find a significant higher subchondral bone density without major alterations of the topographical pattern. It is not possible to define cause and effect, we interpret both as result of higher joint loading.

[The significance of inflammatory changes in the tarsometatarsal joints for development of rheumatic splayed foot: a radiologic follow-up]. / Die Bedeutung entzündlicher Veränderungen der Tarsometatarsal-Gelenke für die Entstehung des rheumatischen Spreizfusses: Eine radiologische Verlaufsstudie.

The involvement of foot joints is a common finding in more than 90% of the patients with rheumatoid arthritis. The typical deformity of the forefoot is the splayfoot with hallux valgus or hallux rigidus and deformities of the lesser toes. 70 feet of 36 patients with rheumatoid arthritis were observed radiologically over a period between 5 years/1 month and 6 years/1 month. The x-rays were analyzed for arthritic changes of the various joints and changes of the foot statics. The question was whether the splay of the forefoot is caused by an arthritis of the metatarsophalangeal or tarsometatarsal joints with a consequent weakening of joint capsules and ligaments, or statistically by a flattening of the longitudinal arch owing to arthritic changes of the hindfoot. The statistic analysis showed that the splay of the forefoot appears between the first and second metatarsal bones. The arthritis of the tarsometatarsal joints II-IV could be identified as a statistically significant factor for the development of a splayfoot in rheumatoid arthritis. The influence of arthritic changes of the tarsometatarsal joints I and V was striking, but not statistically significant. The arthritis of the tarsometatarsal joints caused a flattening of the transverse arch already at an early stage. An arthritis of the metatarsophalangeal joints and the flattening of the longitudinal arch with arthritides of the rear foot had no statistically significant influence on the forefoot. From the results, we must draw the conclusions that orthopedic aids like shoe supports with retrocapital metatarsal bars should be recommended already at an early stage of the disease and that the support of the longitudinal arch is not sufficient to prevent a splayfoot.

NADPH: ferredoxin oxidoreductase acts as a paraquat diaphorase and is a member of the soxRS regulon.

Soluble extracts of Escherichia coli contain four NADPH:paraquat diaphorases that were separable by anion-exchange HPLC over Mono Q. One of these was induced when the cells were exposed to paraquat. This was the case in a soxRS-competent strain but not in a soxRS-null strain, while a soxRS-constitutive strain overexpressed this diaphorase without the stimulus of exposure to paraquat. This NADPH:paraquat diaphorase could use cytochrome c or nitroblue tetrazolium as an electron acceptor, whereas O2 was a relatively poor acceptor. This diaphorase was identified as the NADPH:ferredoxin reductase. A role for reduced ferredoxin and flavodoxin in the adaptive soxRS response to oxidative stress and in the regulation of the redox status of soxR is discussed.

Membrane topology and mutational analysis of the TolQ protein of Escherichia coli required for the uptake of macromolecules and cell envelope integrity.

TolQ is a 230-amino-acid protein required to maintain the integrity of the bacterial envelope and to facilitate the import of both filamentous bacteriophage and group A colicins. Cellular fractionation experiments showed TolQ to be localized to the cytoplasmic membrane. Bacteria expressing a series of TolQ-beta-galactosidase and TolQ-alkaline phosphatase fusion proteins were analyzed for the appropriate enzyme activity, membrane location, and sensitivity to exogenously added protease. The results are consistent with TolQ being an integral cytoplasmic membrane protein with three membrane-spanning regions. The amino-terminal 19 residues as well as a small loop in the 155 to 170 residue region appear exposed in the periplasm, while the carboxy terminus and a large loop after the first transmembrane region are cytoplasmic. Amino-terminal sequence analysis of TolQ purified from the membrane revealed the presence of the initiating formyl methionine group, suggesting a rapid translocation of the amino-terminal region across the cytoplasmic membrane. Analysis of various tolQ mutant strains suggests that the third transmembrane region as well as parts of the large cytoplasmic loop are necessary for activity.

The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles.

The 2.2 A resolution crystal structure of recombinant human manganese superoxide dismutase, a homotetrameric enzyme that protects mitochondria against oxygen-mediated free radical damage, has been determined. Within each subunit, both the N-terminal helical hairpin and C-terminal alpha/beta domains contribute ligands to the catalytic manganese site. Two identical 4-helix bundles, symmetrically assembled from the N-terminal helical hairpins, form novel tetrameric interfaces that stabilize the active sites. Structurally altered polymorphic variants with reduced activity, such as tetrameric interface mutant Ile-58 to Thr, may produce not only an early selective advantage, through enhanced cytotoxicity of tumor necrosis factor for virus-infected cells, but also detrimental effects from increased mitochondrial oxidative damage, contributing to degenerative conditions, including diabetes, aging, and Parkinson's and Alzheimer's diseases.

Visualization of purified fibronectin-transglutaminase complexes.

It has been reported previously (Turner, P.M., and Lorand, L. (1989) Biochemistry 28, 628-635) that human erythrocyte transglutaminase forms a noncovalent complex with human plasma fibronectin near its collagen-binding domain. In the present study, we show by nondenaturing electrophoresis that guinea pig liver transglutaminase, similarly to the erythrocyte enzyme, forms a complex with human fibronectin. Studies of anisotropic shifts of fluorescein-labeled liver and erythrocyte transglutaminases, upon addition of fibronectin, indicated that both transglutaminases bind to fibronectin with a stoichiometry of about 2:1. Polymerization of fibrinogen by human erythrocyte transglutaminase was inhibited after complex formation with fibronectin. Complexes of fibronectin with either erythrocyte or liver transglutaminase were isolated by glycerol gradient zone sedimentation and examined by rotary shadowing electron microscopy. The globular transglutaminase could be readily identified binding to the thin fibronectin strand. The binding site for transglutaminase was within 5-10 nm of the N terminus of fibronectin, consistent with its proximity to the collagen-binding domain. Under some experimental conditions, the complex of fibronectin with erythrocyte transglutaminase appeared as a ring-shaped structure in which two transglutaminase molecules had probably dimerized. The molecular weight of the erythrocyte transglutaminase was determined by sedimentation equilibrium to be 71,440 +/- 830.

[The styloid syndrome. Differential diagnosis of degenerative diseases of the cervical vertebrae--case report with literature review]. / Das Styloid-Syndrom. Eine Differentialdiagnose degenerativer Erkrankungen der Halswirbelsäule--Kasuistik mit Literaturübersicht.

Elongated Styloid Process Syndrome requires its consideration in differential diagnosis of degenerative disease of the cervical spine. Radiating pain on certain movements of the cervical spine is a symptom of an elongated styloid process as well. First basic anatomy and pathology, symptoms and differential diagnosis of the elongated styloid syndrome are discussed. A case history is presented together with X-rays of the cervical spine and images of three dimensional CT-reconstruction to show the full length of an elongated styloid process.

TolA: a membrane protein involved in colicin uptake contains an extended helical region.

The group A colicins and the DNA of many single-stranded filamentous bacteriophage are able to use combinations of the Tol proteins to gain entrance into or across the membrane of Escherichia coli. The TolA protein is a 421-amino acid residue integral membrane protein composed of three domains. Domain I, consisting of the amino-terminal 47 amino acids, contains a 21-residue hydrophobic segment that anchors the protein in the inner membrane. The remaining 374 amino acids, containing the other two domains, reside in the periplasmic space. Domain III, consisting of the carboxyl-terminal 120 residues, is considered to be the functional domain based on the location of the tolA592 deletion mutation. The internal 262 amino acids comprise domain II, which connects domains I and III together via short regions of polyglycine. It contains a large number of 3- to 5-residue polyalanine stretches, many of which have a repeat of the sequence Lys-Ala-Ala-Ala-(Glu/Asp). Circular dichroism analysis of different portions of TolA show domain II to be predominantly alpha-helical in structure while domain III contains approximately 10% helical structure.

Phosphate, not superoxide dismutase, facilitates electron transfer from ferrous salts to cytochrome c.

Peterson and Eaton (1989, Biochem. Biophys. Res. Commun. 165, 164-167) reported that the copper- and zinc-containing, but not the manganese-containing, superoxide dismutase catalyzes the reduction of cytochrome c by ferrous salts. This activity, erroneously attributed to the enzyme, is now shown to have been due to inorganic phosphate.

In vivo competition between iron and manganese for occupancy of the active site region of the manganese-superoxide dismutase of Escherichia coli.

Three forms of the dimeric manganese superoxide dismutase (MnSOD) were isolated from aerobically grown Escherichia coli which contained 2 Mn, 1 Mn and 1 Fe, or 2 Fe, respectively. These are designated Mn2-MnSOD, Mn,Fe-MnSOD, and Fe2-MnSOD. Substitution of iron in place of manganese, eliminated catalytic activity, decreased the isoelectric point, and increased the native electrophoretic anodic mobility, although circular dichroism, high performance liquid chromatography gel exclusion chromatography, and sedimentation equilibrium revealed no gross changes in conformation. Moreover, replacement of iron by manganese restored enzymatic activity. Fe2-MnSOD and the iron-superoxide (FeSOD) of E. coli exhibit distinct optical absorption spectra. These data indicate that the active site environments of E. coli MnSOD and FeSOD must differ. They also indicate that competition between iron and manganese for nascent MnSOD polypeptide chains occurs in vivo, and copurification of these variably substituted MnSODs can explain the substoichiometric manganese contents and the variable specific activities which have been reported for this enzyme.

[Solitary infantile myofibromatosis of the sacrum]. / Solitäre infantile Myofibromatose des Os sacrum.

The infantile myofibromatosis is the most common fibrous tumor of infancy. One may find solitary lesions of dermal, visceral, musculoskeletal and subcutaneous tissues. Multiple lesions without visceral involvement generally take a benign course. Because the lesion is commonly known only to pathologists, infantile myofibromatosis is often misdiagnosed and underreported. Therefore we present a review of the pathology and symptoms of infantile myofibromatosis together with a case report of a solitary lesion of bone.