A characterization of glycinergic receptors present in cultured rat medullary neurons.

1. Whole-cell current responses to bath application of glycine, beta-alanine, and taurine were studied in medullary neurons cultured from embryonic rats. 2. Two current components were seen in the responses to bath application of agonist, one component that desensitized and another that did not. 3. The two current components have different dose-response characteristics, with the nondesensitizing component being activated more effectively at lower concentrations than the desensitizing component and also reaching its peak at lower concentrations. The agonist concentrations producing half-maximal responses are 26 +/- 4 (SE, n = 6) and 69 +/- 17 (n = 7) microM for the nondesensitizing and desensitizing components, respectively, for glycine; 54 +/- 7 (n = 9) and 127 +/- 37 (n = 7) microM for beta-alanine; and 153 +/- 24 (n = 9) 443 +/- 99 (n = 3) microM for taurine. Thus, for each component, the order of potency is glycine greater than beta-alanine greater than taurine. 4. When total responses to glycine, beta-alanine, and taurine are compared in the same cells, taurine and beta-alanine are less potent agonists than glycine, with relative potencies of 1:0.4:0.1 for glycine-beta-alanine-taurine. 5. The desensitizing component is more sensitive to strychnine than the nondesensitizing one. The strychnine concentrations that block 50% of the response to a control dose of agonist are 15 and 500 nM for the desensitizing and nondesensitizing components, respectively, for glycine; 60 nM and 1 microM for beta-alanine; and 18 and 500 nM for taurine. 6. The complete occlusion between the responses to glycine and beta-alanine or glycine and taurine suggests that these agonists activate the same receptors. 7. The two current components may be manifestations of one receptor population with complicated kinetics or two independent receptor populations.     

Memory CD8+ T cell differentiation: initial antigen encounter triggers a developmental program in naïve cells

The rules that govern memory T cell differentiation are not well understood. This study shows that after antigenic stimulation na?ve CD8+ T cells become committed to dividing at least seven times and differentiating into effector and memory cells. Once the parental na?ve CD8+ T cell had been activated, this developmental process could not be interrupted and the daughter cells continued to divide and differentiate in the absence of further antigenic stimulation. These data indicate that initial antigen encounter triggers an instructive developmental program that does not require further antigenic stimulation and does not cease until memory CD8+ T cell formation.     

An innovative, longitudinal program to teach residents about end-of-life care.

At the University of California, Irvine Medical Center, an end-of-life curriculum was implemented in 2000 for an internal medicine residency utilizing a longitudinal approach that allowed residents to follow patients through their entire hospice experience. An elective home hospice rotation was developed for which third-year residents served as primary care physicians for patients at the end of life over a one-year period. Residents were supervised by faculty who were hospice medical directors. They also learned through case vignettes, quarterly meetings, textbook reading, and personal projects. From July 2000 to June 2002, residents demonstrated positive attitudes towards hospice care and recommended the rotation highly (mean 8.86 on a scale of 1-10). The rotation grew in popularity from six initial residents to ten residents the next year, and has since become a mandatory rotation for all senior residents. A 360-degree evaluation uniformly indicated positive resident performance from the hospice team (mean scores 7.56-8.69 on a 1-9 scale), family (mean scores 9.3-9.7 on a 1-10 scale) and faculty (mean scores 7.29-7.72 on a 1-9 scale). Residents were also pleased with the level of teaching (mean 8.86 on a scale of 1-10) and felt that the patient care load was "just right." Their knowledge improved by 8% (p =.0175). In conclusion, a longitudinal hospice rotation was implemented that fulfilled curricular goals without undue burden on the residents or residency program.     

Absence of group II phospholipase A2, a Paneth cell marker, from the epididymis

Paneth cell-like metaplasia has been reported in the epithelium of the epididymis and prostatic adenocarcinomas. We studied the expression of group II phospholipase A2 (PLA2), a marker of Paneth cell differentiation, in six orchiectomy specimens with Paneth cell-like metaplasia. Both immunohistochemistry for group II PLA2 protein and in situ hybridization for the mRNA of group II PLA2 gave negative results in all six cases but positive reaction for lysozyme. The results show that the cells of the Paneth cell-like metaplasia are not true Paneth cells.     

Phosphate glasses for tissue engineering: Part 2. Processing and characterisation of a ternary-based P2O5-CaO-Na2O glass fibre system

This paper presents the results of a study of the thermal properties, solubility and dimensions of a range of phosphate-based glass fibres (PB-GFs). The glass compositions were limited by fixing the P2O5 content to 45, 50 and 55 mol%, and varying the CaO mol% at 30, 35 and 40. PB-GFs were obtained from the 50 and 55 mol% P2O5 compositions; however, we were unable to obtain fibres from the 45 mol% compositions. This was linked to the cross-linked density, network connectivity and average chain length of the compositions studied. With regards to thermal parameters investigated, initial data showed an increase of the Tg and crystallisation temperatures with increasing CaO mol% at each fixed phosphate content. A decrease in Tg temperatures was also observed with increasing P2O5 content to 55 mol%. The crystallisation temperatures obtained for compositions with fixed phosphate at 55 mol%, showed a reverse pattern, with a decrease in values as compared to the fixed 50 mol% phosphate compositions. The diameters of the fibres all decreased with increasing RPMs as expected, and the solubility also increased with increasing RPMs. This was related to the increased surface area of the higher RPM fibres. There was also a decrease seen in solubility with increasing CaO mol%.     

Effect of iron on the surface, degradation and ion release properties of phosphate-based glass fibres

Phosphate-based glass fibres (PGF) have the unique characteristic of being completely soluble in an aqueous environment, releasing bioactive and biocompatible ions. They have been proposed as tissue engineering scaffolds for craniofacial skeletal muscle regeneration, where myoblasts are seeded directly onto the fibres. Studies have shown that these cells have a preference in their initial attachment to fibres of certain composition and size, which in turn control the rate of degradation. This study investigated the relationship between the surface properties, degradation properties and ion release (cationic and anionic species) by altering the chemical composition of the PGF. Iron oxide (Fe2O3) was incorporated into glasses containing P2O5 (50 mol%), CaO (30 mol%) and Na2O (20 mol%). Six glass compositions with Fe2O3 ranging from 0 to 5 mol% by replacing the equivalent Na2O mol% were investigated. Contact angle measurements showed that polar interactions occurring on the glass surfaces diminished with increasing Fe2O3 content. This behaviour was reflected in the estimated surface energies of the glasses, where the overall surface energy decreased with increasing Fe2O3 content due to the decrease in polar or acid/base component. The incorporation of up to 5 mol% Fe2O3 into PGF resulted in a significant reduction in the degradation rate (by two orders of magnitude), which can be related to the formation of more hydration resistant P-O-Fe bonds. However, the degradation rate increased with decreasing fibre diameter (comparing average diameters of 31.6 +/- 6.5 microm versus 13.1 +/- 1.3 microm) for a given mass of fibre, and this is related to the surface area to volume ratio. Taken together the results suggest that fibres with the larger diameters and containing 3-5 mol% Fe2O3 could initially be a more durable scaffold than ones with 1 or 2 mol% Fe2O3 for initial cell attachment.     

Association of DR4 with pemphigus

HLA typing for the A, B, C, and D locus antigens was performed on 65 patients with pemphigus vulgaris and on 558 controls living in the Los Angeles area. The patients were divided into several categories. These included Jewish and non-Jewish patients, patients with only mucous membrane involvement, only skin or both mucous membrane and skin involvement, and those with a single-episode or recurrent disease. Depending on the highest titer of anti-intercellular cement substance antibody titer, the patients were categorized into those whose titers were 0-80, 160-320, and 640 or greater. A statistically increased incidence of HLA-A25, HLA-B38, and HLA-DR4 antigens was observed in patients compared to controls. This incidence was significantly higher in Jewish compared to non-Jewish patients. The correlations were insignificant in the group with an antibody titer of 0-80, but significant in those with a titer of 160-320, and even more significant in those with titers greater than 640. No significant differences were present between patients who had a single-episode or recurrent disease or in those that had only mouth or only skin involvement. In all categories tested, the association was stronger with DR4 than with A26 or B38. DR4 was present equally in B38-positive and B38-negative patients. The primary association of pemphigus vulgaris may be with the DR4 antigen, and it may be a marker for the severity of the disease.