Biomedical subjects

Bruce E Cohen

Publications and source records attributed to Bruce E Cohen.

5 recordsLinked to original sources

PubMed2005

A fluorescent probe designed for studying protein conformational change.

The usefulness of fluorescence in studying protein motions derives from its sensitivity, kinetic resolution, and compatibility with both live cells and physiological assays. Recent advances in microscopy and membrane protein purification have permitted the observation of fluorescence changes that accompany the functional transitions of complex eukaryotic membrane proteins. These techniques rely on probes that can clearly report the environmental changes of specific residues, but most commonly available side-chain-reactive probes are not well suited for this purpose. Here, we introduce a red Cys-reactive probe, aminophenoxazone maleimide (APM), designed with improved chemical and spectral properties for reporting protein conformational change. APM is compact, uncharged, and has a short linker between probe and protein, all of which ensure that it can closely track the motions of the side chain to which it is attached. It undergoes large polarity-dependent changes in Stokes shift, as well as large bathochromic shifts in both excitation maximum (from 521 nm in toluene to 598 nm in water) and emission maximum (580 nm to 633 nm). These polarity-dependent spectral changes offer a potentially simple means of relating fluorescence to local structure and motion, although they are partially offset by some complicating factors in APM fluorescence. We find that, like a rhodamine maleimide, APM senses the conformational changes underlying voltage sensing in the Shaker potassium channel, and it is superior at a site that shows limited reactivity to the rhodamine. The spectral characteristics of APM can also report subtle differences between aqueous positions in purified preparations of the beta2 adrenergic receptor.

Fluorescent Dyes↗

PubMed2005

Evaluation of hallux alignment and functional outcome after isolated tibial sesamoidectomy.

BACKGROUND: Functional loss and clinical evidence of hallux malalignment have been reported to follow isolated tibial sesamoidectomy. METHODS: Thirty-two patients with isolated tibial sesamoidectomies were identified. Patients with a diagnosis of peripheral neuropathy, diabetes mellitus, inflammatory arthropathy or previous foot surgery were excluded as were patients who had concomitant joint realignment procedures. Twenty patients were available for followup with the Short Form-36 (SF-36), Foot Function Index (FFI) disability scale, visual analog scale (VAS), and questionnaire at an average of 62 (range 10 to 157) months after surgery. Fourteen patients returned for physical examination, radiographs, and pedographic and isokinetic examination. RESULTS: Physical examination of the 14 patients did not reveal any significant change in clinical alignment, range of motion or tenderness. Preoperative and postoperative comparison radiographs did not reveal significant differences in the intermetatarsal (IM) angle, hallux valgus (HV) angle distal metatarsal articular angle (DMAA), or sesamoid alignment (sesamoid station). Postoperative outcome measurements (VAS, SF36, and FFI) for 20 patients found significant relief of pain and improved functional outcome. Computerized dynamic pedographic measurements (Performance Orthotic) for 12 patients did not reveal any altered plantar pressures in the region of the hallux metatarsophalangeal joint. Isokinetic measurements of ankle plantar flexion push-off strength in eight patients did not reveal significant differences in side-to-side measurements. Eighteen of 20 (90%) patients indicated that they were able to resume all preoperative activities; six (30%) had extreme difficulty or an inability to stand on tip toe, but this did not impact their activities of daily living or their athletic endeavors. Two patients (14.3%) developed transfer metatarsalgia, but only one was symptomatic. CONCLUSION: Isolated tibial sesamoidectomy is a safe and effective treatment for recalcitrant tibial sesamoiditis. Hallux malalignment and deformity resulting in functional loss and change in hallux alignment can be avoided by meticulous surgical technique with repair of the soft tissues.

Adolescent↗

PubMed2003

Answers and questions from the KvAP structures.

The recent landmark structures of KvAP, a voltage-gated potassium (Kv) channel, provide the first high-resolution experimental structural models of this class of proteins. Previous extensive studies of Kv channels provide a means to evaluate and interpret the KvAP structures. In this minireview, we survey different experimental approaches to Kv channels and map these findings to KvAP, showing that the relationship between the KvAP structures and other Kv channels is uncertain.

Animals↗

PubMed2002

Probing protein electrostatics with a synthetic fluorescent amino acid.

Electrostatics affect virtually all aspects of protein structure and activity and are particularly important in proteins whose primary function is to stabilize charge. Here we introduce a fluorescent amino acid, Aladan, which can probe the electrostatic character of a protein at multiple sites. Aladan is exceptionally sensitive to the polarity of its surroundings and can be incorporated site-selectively at buried and exposed sites, in both soluble and membrane proteins. Steady-state and time-resolved fluorescence measurements of Aladan residues at different buried and exposed sites in the B1 domain of protein G suggest that its interior is polar and heterogeneous.

2-Naphthylamine↗

PubMed2002

Viscosupplementation for the arthritic ankle.

HA is, in large part, responsible for the viscoelastic properties of synovial fluid that are critical to normal joint function. In OA, the concentration and molecular weight of HA are diminished. The intra-articular injection of exogenous HA preparations, termed viscosupplementation, has been shown to be safe and efficacious for use in the treatment of OA of the knee. There seem to be many mechanisms of action in addition to the transient restoration of joint fluid viscoelastic properties. These include anti-inflammatory, anabolic, analgesic, chondroprotective, and anticatabolic effects. Anecdotal use in OA of the ankle has been encouraging, but larger scale, controlled studies need to be performed. In addition, long-term investigations will better define the duration of effectiveness that viscosupplementation provides and whether it is a cost-effective modality.

Ankle Joint↗