Probing the Origin of Affinity in the GM1-Cholera Toxin Complex through Site-Selective Editing with Fluorine.

Carbohydrates regulate an inimitable spectrum of biological functions, yet successfully leveraging this therapeutic avenue continues to be frustrated by low affinities with glycan-specific proteins. A conspicuous exception is the interaction of monosialotetrahexosylganglioside (GM1) with the carbohydrate-recognition domain of cholera toxin from : this is one of the strongest protein-carbohydrate interactions known. To establish the importance of a long-discussed key hydrogen bond between C2 of the terminal galactose of GM1 and the B subunit pentamer of cholera toxin (CTB), the total synthesis of a selectively fluorinated GM1 epitope was conducted in 19 steps.

2'-F labelling of ribose in RNAs: a tool to analyse RNA/protein interactions by NMR in physiological conditions.

Protein-RNA interactions are central to numerous cellular processes. In this work, we present an easy and straightforward NMR-based approach to determine the RNA binding site of RNA binding proteins and to evaluate the binding of pairs of proteins to a single-stranded RNA (ssRNA) under physiological conditions, in this case in nuclear extracts. By incorporation of a F atom on the ribose of different nucleotides along the ssRNA sequence, we show that, upon addition of an RNA binding protein, the intensity of the F NMR signal changes when the F atom is located near the protein binding site.

Surface Passivation with a Perfluoroalkane Brush Improves the Precision of Single-Molecule Measurements.

Single-molecule imaging is invaluable for investigating the heterogeneous behavior and interactions of biological molecules. However, an impediment to precise sampling of single molecules is the irreversible adsorption of components onto the surfaces of cover glasses. This causes continuous changes in the concentrations of different molecules dissolved or suspended in the aqueous phase from the moment a sample is dispensed, which will shift, over time, the position of chemical equilibria between monomeric and multimeric components.

Enhancing glycan stability site-selective fluorination: modulating substrate orientation by molecular design.

Single site OH → F substitution at the termini of maltotetraose leads to significantly improved hydrolytic stability towards α-amylase and α-glucosidase relative to the natural compound. To explore the effect of molecular editing, selectively modified oligosaccharides were prepared a convergent α-selective strategy. Incubation experiments in purified α-amylase and α-glucosidase, and in human and murine blood serum, provide insight into the influence of fluorine on the hydrolytic stability of these clinically important scaffolds.

Total Chemical Syntheses of the GM and F-GM Ganglioside Epitopes and Comparative Pre-Clinical Evaluation for Non-Invasive Imaging of Oligodendrocyte Differentiation.

Gangliosides are intimately involved in a plenum of (neuro)inflammatory processes, yet progress in establishing structure-function interplay is frequently hindered by the availability of well-defined glycostructures. Motivated by the ubiquity of the ganglioside GM in chemical neurology, and in particular by its conspicuous presence in myelin, the GM epitope was examined with a view to preclinical validation as a tracer. The suitability of this scaffold for the noninvasive imaging of oligodendrocyte differentiation in Multiple sclerosis is disclosed.

Halogen-directed chemical sialylation: pseudo-stereodivergent access to marine ganglioside epitopes.

Sialic acids are conspicuous structural components of the complex gangliosides that regulate cellular processes. Their importance in molecular recognition manifests itself in drug design ( Tamiflu®) and continues to stimulate the development of effective chemical sialylation strategies to complement chemoenzymatic technologies. Stereodivergent approaches that enable the α- or β-anomer to be generated at will are particularly powerful to attenuate hydrogen bond networks and interrogate function.

Harnessing the Maltodextrin Transport Mechanism for Targeted Bacterial Imaging: Structural Requirements for Improved in vivo Stability in Tracer Design.

Diagnosis and localization of bacterial infections remains a significant clinical challenge. Harnessing bacteria-specific metabolic pathways, such as the maltodextrin transport mechanism, may allow specific localization and imaging of small or hidden colonies. This requires that the intrabacterial tracer accumulation provided by the transporter is matched by high serum stability of the tracer molecule.

[Psychiatric rehabilitation in a secure treatment setting].

Working with severely mentally ill persons within the locked environment of a secure residential treatment facility presents a provocative challenge in attempting to establish a rehabilitative program. The author describes the mission, goals and methods of one of Oregon's newly organized facilities for "hard to place" former state hospital patients. The value of teaching the residents self-control is emphasized.

[Training in preventing assaultive behaviors for psychiatric professionals].

Dangerous behaviors in psychiatric institutions constitute major clinical and administrative problems. Staff competency in dealing with assaultive patients is an important factor in reducing institutional violence. One of the training programs for mental health staff working with dangerous patients is called Professional Assault Response Training (PART).

A new technique for greater trochanteric hip arthroplasty.

This paper describes a new technique for greater trochanteric hip arthroplasty in which the femur is divided at the subtrochanteric level and the upper fragment rotated through 180 degrees to place the greater trochanter deeply in the acetabulum; with the lower limb in the weight-bearing position the fragments are then fixed with a short intramedullary nail. This operation was carried out in a boy aged 4 years 6 months in whom the femoral head and neck had been destroyed by septic arthritis. Ten years later leg-lengthening was performed.

Residual shortening after osteotomy for Perthes' disease. A comparative study.

The residual shortening of the affected limbs in 55 patients treated by subtrochanteric varus derotation osteotomy was compared with that in 71 patients treated with weight-relieving calipers. When last examined, 43 of the former group and 47 of the latter had reached complete or near-complete skeletal maturity. The average follow-up was 9.

Osteoid osteoma of the proximal femur simulating spinal root compression.

In a 6 1/2-year-old boy and a 9 1/2-year-old girl, spinal root compression was suspected on the basis of muscle wasting and weakness, diminished deep tendon reflexes, and severe pain, all in a radicular distribution. However, extensive and invasive neuroradiologic evaluation failed to demonstrate compression of spinal roots. Only several months later was the correct diagnosis of osteoid osteoma reached.

Unusual gas-forming infection with Escherichia coli.

Infections with non-clostridial gas-forming organisms are not often encountered in orthopaedic practice. We present here a case of gas-forming infection with Escherichia coli which occurred 10 months after internal fixation of a closed fracture of the femur in an 84-year-old diabetic woman who suffered from septic nephrolithiasis. The wound infection was considered to have arisen by spread from the organisms of the infected kidney.

Indications for femoral osteotomy in Legg-Calvé-Perthes disease.

A group of children with Legg-Calvé-Perthes disease (LCPD) who underwent femoral osteotomy were analyzed to define further those most likely to respond favorably to this procedure. Treatment was directed to removal of the protruded, flattened, and damaged osteochondral head segment--as delineated by arthrography--from the damaging influence of the lateral acetabular lip and to expose the head to the molding influence of the acetabulum during weight-bearing and motion. This containment of the head was achieved by employing femoral varus-derotation (and sometimes extension) osteotomy.

Simple reconstruction of anteromedial rotational knee stability.

A technically simple operation for the restoration of anteromedial rotational knee stability is described. It involves suturing under tension the posteromedial capsule of the knee joint to the semimembranosus tendon at its insertion into the tibia, with the leg held in full internal rotation and with the knee flexed to 60 degrees. This, in combination with the conservative treatment of meniscal injuries and with tightening of the soft tissue structures over the medial aspect of the knee, restored full or almost full anteromedial stability in the knee in 15 out of 16 young men, observed for an average of 19 months after the operation.

Arthrography as an aid to diagnosis, prognosis and therapy in Legg-Calvé-Perthes' disease.

Measurements of head diameter and acetabulum-head quotient (AHQ) were made on the plain radiographs and corresponding arthrograms of 37 consecutive patients with unilateral Legg-Calvé-Perthes' Disease (L.C.P.

Localized regressive articular cartilage changes in the hip joint of the rabbit following an induced synovitis.

A talcum induced synovitis in the hip joint of the rabbit, which is known to cause articular cartilage hyperplasia followed by femoral head protrusion and joint incongruency, has in the present experiment also been shown to lead to localized regressive articular cartilage changes. The articular cartilage of the hip joints in 40 rabbits was examined histologically, at intervals, following induction of such a talcum synovitis. Regressive changes in the form of loss of surface chondrocytes and glycosaminoglycans sometimes accompanied by fibrillation, were found in the area of the femoral head articular cartilage which had become flattened following the head protrusion.

Arthroscopy of the knee under local anesthesia and controlled pressure-irrigation.

One hundred and forty-two arthroscopies under local anesthesia, using "high pressure" irrigation-suction technique were carried out in 137 patients. With this technique the duration of the examination was shortened, the endoscopic field of vision was enlarged (posterior horn of the menisci could be visualized in most patients), the manipulation of the scope inside the joint cavity was easier and safer. More patients could have been examined during one session.