Rotational diffusion anisotropy of proteins from simultaneous analysis of 15N and 13C alpha nuclear spin relaxation

Current methods of determining the rotational diffusion tensors of proteins in solution by NMR spectroscopy exclusively utilize relaxation rate constants for backbone amide 15N spins. However, the distributions of orientations of N-H bond vectors are not isotropic in many proteins, and correlations between bond vector orientations reduce the accuracy and precision of rotational diffusion tensors extracted from 15N spin relaxation data. The inclusion of both 13C alpha and 15N spin relaxation rate constants increases the robustness of the diffusion tensor analysis because the orientations of the C alpha-H alpha bond vectors differ from the orientations of the N-H bond vectors. Theoretical and experimental results for calbindin D9k, granulocyte colony stimulating factor, and ubiquitin, three proteins with different distributions of N-H and C alpha-H alpha bond vectors, are used to illustrate the advantages of the simultaneous utilization of 13C alpha and 15N relaxation data.     

Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis: a randomized double-blind study

OBJECTIVES: To assess the efficacy of a combination of oral and topical 5-aminosalicylic acid (5-ASA) for the maintenance treatment of ulcerative colitis, we undertook a double-blind randomized clinical trial. METHODS: Patients aged 18 to 65 yr (with disease extent greater than proctitis only) were eligible for inclusion in the study if they met the following criteria: (a) history of two or more relapses in the last year; (b) achievement of remission in the last 3 months (with maintenance of remission for at least 1 month). Patients enrolled in the study were randomly assigned to one of the two following 1-yr treatments: (1) combined therapy with 5-ASA tablets 1.6 g/day and 5-ASA enemas 4 g/100 ml twice weekly; (2) oral therapy with 5-ASA tablets 1.6 g/day and placebo enemas/twice weekly. The main end point of the study was the maintenance of remission at 12 months. RESULTS: Upon completion of the study, relapse occurred in 13 of 33 patients in the combined treatment group versus 23 of 36 patients in the oral treatment group (39 vs 69%; p = 0.036). No significant side effects related to treatment were observed in either group. A simplified pharmacoeconomic analysis shows that this form of combined treatment can have a favorable cost-effectiveness ratio. CONCLUSIONS: Our results indicate that 5-ASA given daily by oral route and intermittently by topical route can be more effective than oral therapy alone. This form of combination treatment can be appropriate for patients at high risk of relapse.     

Appearance and maturation of T-cell subsets during rat thymus ontogeny

This study measured the release of glutamate (Glu) and aspartate (Asp) amino acid transmitters in the ventrocaudal compartment of the rat periaqueductal gray (PAG) following exposure to unilateral peripheral inflammation. The release of endogenous Glu and Asp from the rat ventrocaudal PAG was monitored with the microdialysis technique in unanesthetized, unrestrained rats. There was significant increase (1,300%) in the basal concentrations of Glu release in the 7 days Complete Freund's Adjuvant (CFA) treated group compared to 24 h mineral oil control group. Amino acid release was induced by infusing veratridine (75 microM, a sodium channel activator) directly through the 1 mm long dialysis probe. Perfusion of veratridine into the ventrocaudal PAG resulted in significant elevation of Glu and Asp amino acids. In the 24 h and 7 days CFA treated rats, veratridine-evoked release of Glu was significantly decreased in the lateral ventrocaudal PAG compared to control rats injected with mineral oil (CFA vehicle). The peak minus baseline concentrations of Glu in 24 h and 7 days CFA treated groups decreased 55.7% and 43.9%, respectively. In contrast, The basal and the peak minus baseline concentrations of Asp showed no significant change between control group and 24 h and 7 days CFA treated animals. The results provide direct evidence that Glu excitatory amino acid may be involved in nociception/nociception modulation pathway in the ventrocaudal PAG.     

Torsional injury resulting in disc degeneration in the rabbit: II. Associative changes in dorsal root ganglion and spinal cord neurotransmitter production

An ornamental pet fish was diagnosed with a spinal fracture and subluxation involving truncal vertebrae 5 and 6 (T5-T6) using conventional radiography, nuclear scintigraphy, and computed tomography. Attempts to evaluate the dynamic nature of the lesion using conventional fluoroscopy in the unanesthetized, moving patient were unsuccessful. Adaptation of imaging techniques to accommodate a fish patient was not difficult and diagnostic images were obtained. The use of multiple imaging techniques was useful in the diagnosis and determination of the treatment plan of the spinal fracture in this patient.