Bacillus Calmette-Guérin Packaged for Percutaneous Vaccination Can Be Safely Used for Intravesical Instillation in Patients with Urothelial Carcinoma of the Bladder.

Introduction: Bacillus Calmette-Guérin production is limited worldwide with stuttering shortages affecting patient access. Our institution received 50 vials of bacillus Calmette-Guérin labeled for percutaneous administration, and upon discussion with our clinical team and approval by the Pharmacy and Therapeutics Committee we used the percutaneous formulation in place of the intravesical formulation. We report our experience.

Use of Cannulated Instruments to Localize the Portals in Anterior Ankle Arthroscopy: A Technique Tip.

The use of cannulated instruments under fluoroscopy can improve the localization of the anteromedial and posterolateral portals for use in ankle arthroscopy. This technique is valuable for the less-experienced ankle arthroscopist, in resident education, and for the experienced arthroscopist when surface anatomy palpation and visualization is less than ideal due to soft tissue edema and obesity.

2013 Subtalar Arthroereisis Survey: The Current Practice Patterns of Members of the AOFAS.

Background: Subtalar arthroereisis (SA) has been a procedure used for the correction of painful flexible flatfoot deformity in adults and children. Clinical studies of patients who had a SA are sparse and with mixed results and variable indications. The purpose of this study was to determine the current practice among orthopaedic foot and ankle specialists regarding SA.

Comparison of two fixation methods for arthrodesis of the calcaneocuboid joint: a biomechanical study.

Background: The traditional fixation for a calcaneocuboid (CC) arthrodesis in triple arthrodesis is with a 6.5-mm cancellous screw. This procedure can be technically challenging.

Amino acids as biomarkers in the SOD1(G93A) mouse model of ALS.

The development of therapies for Amyotrophic Lateral Sclerosis (ALS) has been hindered by the lack of biomarkers for both identifying early disease and for monitoring the effectiveness of drugs. The identification of ALS biomarkers in presymptomatic individuals might also provide clues to the earliest biochemical correlates of the disease. Previous attempts to use plasma metabolites as biomarkers have led to contradictory results, presumably because of heterogeneity in both the underlying genetics and the disease stage in the clinical population.

Effect of sex on lifespan, disease progression, and the response to methionine sulfoximine in the SOD1 G93A mouse model for ALS.

Objective: To investigate the role of sex and the role of ammonia and amino acid metabolism, specifically the activity of glutamine synthetase, in survival and disease progression in amyotrophic lateral sclerosis.

Methods: We tested treatment with methionine sulfoximine (MSO) on the lifespan and neuromuscular ability of male and female SOD1 mice as measured by their ability to maintain their grip on an inverted wire grid. We also tested the effects of castration and ovariectomization on those measurements.

Fluoroscopic method for localization of the anteromedial portal for use in ankle arthroscopy: technique tip.

Ankle arthroscopy has become a standard surgical technique for the treatment of many ankle pathologies. Over the past 30 years, the technique has undergone modification and standardization in order to improve surgical performance and outcomes. In contrast to the ankle joint, the hip joint is a deep joint, which makes visualization and palpation of the topographical anatomy quite difficult.

A glutamine synthetase inhibitor increases survival and decreases cytokine response in a mouse model of acute liver failure.

Background: Acute liver failure (ALF) can be induced in mice by administering Escherichia coli lipopolysaccharide (LPS) and D-galactosamine (D-GalN), which induce an inflammatory response involving tumour necrosis factor (TNF)-α production and a hepatocyte-specific transcriptional block. Under these conditions, binding of TNF-α to its cognate receptor on hepatocytes eventually leads to their apoptosis.

Aims: As part of an effort to identify drugs to treat this disease model, we have investigated whether the glutamine synthetase inhibitor methionine sulfoximine (MSO) could play a protective role, given its effectiveness in the inhibition of brain swelling associated with hyperammonaemia.

Methionine sulfoximine, an inhibitor of glutamine synthetase, lowers brain glutamine and glutamate in a mouse model of ALS.

In an effort to alter the levels of neurochemicals involved in excitotoxicity, we treated mice with methionine sulfoximine (MSO), an inhibitor of glutamine synthetase. Since glutamate toxicity has been proposed as a mechanism for the degeneration of motor neurons in a variety of neurodegenerative diseases, we tested the effects of MSO on the transgenic mouse that overexpresses the mutant human SOD1(G93A) gene, an animal model for the primary inherited form of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS). This treatment in vivo reduced glutamine synthetase activity measured in vitro by 85%.

A surgical approach for flexible flatfeet in adults including a subtalar arthroereisis with the MBA sinus tarsi implant.

Background: The purpose of this study was to determine the functional outcomes and radiographic results of adult patients who had an operation for flexible flatfeet without any hindfoot osteotomies or fusions.

Methods: Twenty-eight feet in 23 patients with problems caused by their flexible flatfoot deformities had reconstructive foot and ankle surgery that included a subtalar arthroereisis (the restriction of the range of motion of a joint) with the Maxwell-Brancheau Arthroereisis (MBA) sinus tarsi implant. The American Orthopedic Foot and Ankle Society (AOFAS) Hindfoot Scale and a patient assessment questionnaire were obtained from all patients before surgery and at final follow-up.

Activity of the yeast Tat2p tryptophan permease is sensitive to the anti-tumor agent 4-phenylbutyrate.

4-Phenylbutyrate (PB) induces differentiation and is being intensively studied as a treatment for brain, prostate, breast, and hematopoietic cancer. While many different primary targets for PB have been proposed, the mechanism by which it causes cellular differentiation remains unknown. To identify the primary cellular target, we investigated its effects on Saccharomyces cerevisiae and showed that it inhibits tryptophan transport.

Water-mediated hydrogen-bonded network on the cytoplasmic side of the Schiff base of the L photointermediate of bacteriorhodopsin.

The L intermediate in the proton-motive photocycle of bacteriorhodopsin is the starting state for the first proton transfer, from the Schiff base to Asp85, in the formation of the M intermediate. Previous FTIR studies of L have identified unique vibration bands caused by the perturbation of several polar amino acid side chains and several internal water molecules located on the cytoplasmic side of the retinylidene chromophore. In the present FTIR study we describe spectral features of the L intermediate in D(2)O in the frequency region which includes the N-D stretching vibrations of the backbone amides.

Immunosuppressant-like effects of phenylbutyrate on growth inhibition of Saccharomyces cerevisiae.

Phenylbutyrate (4-phenylbutyric acid; PB) and its metabolite, phenylacetate, are effective anti-neoplastic agents in tissue culture and have shown promise in clinical trials for a variety of neoplasms. PB is a drug of remarkably low toxicity that acts in vitro as a differentiating agent, causing reversion of the transformed phenotype by an unknown mechanism. We attempted to identify the cellular target(s) for PB using Saccharomyces as a model.

Changes in hydrogen bonding and environment of tryptophan residues on helix F of bacteriorhodopsin during the photocycle: a time-resolved ultraviolet resonance Raman study.

Protein structural changes during the photocycle of bacteriorhodopsin were examined by time-resolved ultraviolet resonance Raman (UVRR) spectroscopy. Most of the 244-nm UVRR difference signals of Trp were assigned to either Trp182 or Trp189 using the Trp182 --> Phe and Trp189 --> Phe mutants. The W17 mode of Trp182 shows a wavenumber downshift in the M(1) --> M(2) transition, indicating an increase in hydrogen bonding strength at the indole nitrogen.

Conformational change of the E-F interhelical loop in the M photointermediate of bacteriorhodopsin.

The conformation of the structured EF interhelical loop of bacteriorhodopsin and its change in the M photointermediate were assessed by measuring the rate of reaction of 16 single engineered cysteine residues along the loop with water-soluble sulfhydryl reagents. The exposure to the bulk in the unilluminated state determined with the cysteine reaction correlated well with the degree of access to water calculated from the crystallographic structure of the loop. The EF-loop should be affected by the well-known outward tilt of helix F in the M and N intermediates of the photocycle.