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Biomedical subjects

Lars Neumann

Publications and source records attributed to Lars Neumann.

11 recordsLinked to original sources
PubMed2005

Reconstruction of the deltoid and acromion after failed acromionectomy.

UNLABELLED: Ten patients who had reconstruction of the acromion and deltoid in a painful dysfunctional shoulder after an acromionectomy were reviewed with respect to pain, range of motion, strength, patients' satisfaction, and complications. There were four total acromionectomies, five subtotal acromionectomies, and one partial acromionectomy. The retracted deltoid and defect of the bony acromion were reconstructed with a composite graft consisting of tricortical iliac bone with fascia lata. At an average followup of 58 months, the mean active forward flexion improved from 53 degrees to 122 degrees. All patients reported considerable relief of pain and three had no pain; however, the patients who had a supplementary cuff repair had poor results. The average UCLA score of the patients improved from 6.6 to 26.3. The score of the patients with intact rotator cuffs improved from 7.0 to 32.0, whereas patients who had rotator cuff tears had scores that improved from 6.2 to 20.4. Our clinical results suggest that reconstruction of the acromion and deltoid using an iliac bone graft and fascia in failed acromionectomy can lead to relief of pain and the improvement of shoulder function. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series-no, or historical control group).

Acromion↗
PubMed2003

Metal-chelating amino acids as building blocks for synthetic receptors sensing metal ions and histidine-tagged proteins.

Protein structure and function rely on a still not fully understood interplay of energetic and entropic constraints defined by the permutation of the twenty genetically encoded amino acids. Many attempts have been undertaken to design peptide-peptide interaction pairs and synthetic receptors de novo by using this limited number of building blocks. We describe a rational approach to creating a building block based on a tailored metal-chelating amino acid. Nepsilon,Nepsilon-bis(carboxymethyl)-L-lysine can be flexibly introduced into peptides by 9-fluorenylmethoxycarbonyl solid-phase chemistry. The corresponding metal-chelating peptides act as metal sensors and synthetic receptors for histidine-tagged proteins. These biochemical tweezers will open new ways to control protein-protein interactions, to design peptide-based interaction pairs, or to generate switchable protein function.

Amino Acids↗
PubMed2002

Thermodynamics of peptide binding to the transporter associated with antigen processing (TAP).

The ATP-binding cassette (ABC) transporter TAP plays an essential role in antigen processing and immune response to infected or malignant cells. TAP translocates proteasomal degradation products from the cytosol into the endoplasmic reticulum, where MHC class I molecules are loaded with these peptides. Kinetically stable peptide-MHC complexes are transported to the cell surface for inspection by cytotoxic T lymphocytes. The transport cycle of TAP is initiated by peptide binding, which is responsible for peptide selection and for stimulation of ATP-hydrolysis and subsequent translocation. Here we have analysed the driving forces for the formation of the peptide-TAP complex by kinetic and thermodynamic methods. First, the apparent peptide association and dissociation rates were determined at various temperatures. Strikingly, very high activation energies for apparent association (E(a)(ass)=106 kJmol(-1)) and dissociation (E(a)(diss)=80 kJmol(-1)) of the peptide-TAP complex were found. Next, the temperature-dependence of the peptide affinity constants was investigated by equilibrium-binding assays. Along with calculations of free enthalpy deltaG, enthalpy deltaH and entropy deltaS, a large positive change in heat capacity was resolved (deltaC degrees =23 kJmol(-1)K(-1)), indicating a fundamental structural reorganization of the TAP complex upon peptide binding. The inspection of the conformational entropy reveals that approximately one-fourth of all TAP residues is rearranged. These thermodynamic studies indicate that at physiological temperature, peptide binding is endothermic and driven by entropy.

ATP-Binding Cassette Transporters↗
PubMed2002

Functional immobilization of a ligand-activated G-protein-coupled receptor.

G-protein-coupled receptors (GPCRs) mediate the majority of cellular responses to hormones and neurotransmitters. They are the largest family of receptors in the human genome and constitute the largest class of targets for drug discovery. To facilitate studies of GPCR activation and interactions with other proteins, we developed a simple method to immobilize a functional, detergent-solubilized GPCR on gold and glass surfaces. The beta(2) adrenergic receptor (beta(2)AR), a prototypical GPCR, was purified and labeled with a reporter fluorophore at a conformationally sensitive site. The detergent-soluble fluorescent beta(2)AR was immobilized through its amino-terminal FLAG epitope on a surface layered with biotinylated bovine serum albumin, avidin, and biotinylated M1 antibody. Agonist activation of the beta(2)AR was monitored in real time by fluorescence microscopy. This approach will make it possible to study conformational dynamics of single immobilized receptors and to generate arrays of functional GPCRs for novel high-throughput screening strategies.

Animals↗
PubMed2002

Analysis of biomolecular interactions using a miniaturized surface plasmon resonance sensor.

A commercially available miniaturized surface plasmon resonance sensor has been investigated for its applicability to biological interaction analysis. The sensor was found to exhibit excellent repeatability and linearity for high-refractive index solutions and good reproducibility for the binding of proteins. Its detection limit for the monoclonal antibody M1 was found to be 2.1 fmol, which corresponds to a surface concentration of 21 pg/mm2. Simple surface immobilization procedures relying on biotin/avidin or glycoprotein/lectin chemistry have been explored. Equilibrium dissociation constants for the binding of the FLAG peptide to its monoclonal antibody (M1) and for the binding of concanavalin A to a glycoprotein have been determined. The close agreement of these measurements with values obtained by surface fluorescence microscopy and fluorescence correlation spectroscopy helps to validate the use of this device. Thus, this sensor shows promise as an inexpensive, portable, and accurate tool for bioanalytical applications in laboratory and clinical settings.

Animals↗
PubMedDate not supplied

Heterotopic ossification after primary shoulder arthroplasty.

We have assessed the incidence of heterotopic ossification (HO) after primary shoulder joint replacement in 126 shoulders; 58 patients had hemiarthroplasty, and 68 had total shoulder joint replacement. HO developed to a minor extent in 15% of patients (19/126). There was no statistical difference between hemiarthroplasty or total shoulder replacement or between male and female patients. Patients with cuff tear arthropathy were the only group with an increased risk (36.4% [4/11]) of having HO develop. In patients with osteoarthritis, fractures, or rheumatoid arthritis, HO occurred in less than 14.5% (15/115). Nonsteroidal anti-inflammatory drugs (NSAIDs) did not appear to have any effect on HO as in hip replacement, as HO developed in 15.15% of patients having NSAIDs postoperatively and in 15.05% of patients without NSAIDs. Prophylaxis of HO with NSAIDs seems only to be indicated in patients with cuff tear arthropathy.

Adult↗
PubMedDate not supplied

Scapulothoracic fusion for painful winging of the scapula in nondystrophic patients.

A modified technique of scapulothoracic fusion was used in 6 patients who did not have muscular dystrophy and who were later evaluated clinically. The cause of the painful winging of the scapula was traumatic disruption of the trapezius and the accessory nerve in 3 patients, injury to the brachial plexus in 2, and Sprengel's deformity in 1. To obtain fusion, double wires were passed around each of 4 ribs. A Rush pin was then contoured to fit the curvature of the scapula, and the wires were passed through the scapula and tied over the Rush pin with bone graft. The mean age of the patients was 30 years (range, 22-39 years), with a mean follow-up of 49 months. The mean increase in elevation was 18 degrees with significant pain relief. The medium-term results showed that this operation was successful in achieving stability of the scapula while improving pain and function in patients without facioscapulohumeral dystrophy.

Adult↗
PubMedDate not supplied

One-stage arthroplasty of the ipsilateral shoulder and elbow.

Twenty 1-stage ipsilateral shoulder and elbow joint replacements were performed in 17 patients from 1988 to 1998 in the Nottingham Shoulder and Elbow Unit, Nottingham, England. There were 12 women and 5 men with a mean age at operation of 57 years. All 17 patients had rheumatoid arthritis. The indication for performing the 2 joint replacements in 1 stage was severe symptomatic involvement of both joints. The shoulder was replaced first, with the patient being repositioned and redraped for the elbow replacement. The follow-up averaged 5 years 2 months (range, 23 months to 13 years 8 months). All patients had significant pain relief and improvement in function, and 12 of the 15 patients reviewed would have been prepared to have the same procedure on the other side, if it became necessary (in 3, this had been done). The procedure offers major advantages because the number of anesthetics is reduced, it is more cost-effective, and it facilitates functional rehabilitation.

Adult↗