ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels.

The tarantula venom peptides ProTx-I and ProTx-II inhibit voltage-gated sodium channels by shifting their voltage dependence of activation to a more positive potential, thus acting by a mechanism similar to that of potassium channel gating modifiers such as hanatoxin and VSTX1. ProTx-I and ProTx-II inhibit all sodium channel (Nav1) subtypes tested with similar potency and represent the first potent peptidyl inhibitors of TTX-resistant sodium channels. Like gating modifiers of potassium channels, ProTx-I and ProTx-II conform to the inhibitory cystine knot motif, and ProTx-II was demonstrated to bind to sodium channels in the closed state. Both toxins have been synthesized chemically, and ProTx-II, produced by recombinant means, has been used to map the interaction surface of the peptide with the Nav1.5 channel. In comparison, beta-scorpion toxins activate sodium channels by shifting the voltage dependence of activation to more negative potentials, and together these peptides represent valuable tools for exploring the gating mechanism of sodium channels.     

Race and ethnic differences and human figure drawings: clinical utility of the DAP:SPED.

This study examined race and ethnic differences on the Draw A Person: Screening Procedure for Emotional Disturbance (DAP:SPED; Naglieri, McNeish, & Bardos, 1991) for youths 6 though 17 years of age for 2 matched samples. Samples were drawn from the DAP:SPED nationally representative standardization sample and matched on gender, grade, and school classroom. No statistically significant differences were found for big figure, small figure, or shading item composites. A statistically significant difference was found between Black-White pairs on figure omissions but showed a small effect size (d value = .25). Further, no statistically significant differences were found between the DAP:SPED Total T scores for Black and White youth (M = 47.67, SD = 10.09; N =138) or Hispanic and White youth (M = 48.20, SD = 9.56; N = 59), showing very small effect sizes. In addition, equivalence testing showed similarities across race and ethnic pairs for all composites and DAP:SPED total score, lending preliminary support to the DAP:SPED's clinical utility as a measure that yields similar scores across these groups.     

PILOT PROJECTS TO STIMULATE ADVERSE DRUG REACTION REPORTING

Schemes for stimulating adverse drug reporting are described with particular emphasis on a recently introduced Mississippi Adverse Drug Reaction Reporting Programme.     

The prognostic value of E-cadherin, α-, β- and γ-catenin in bladder cancer patients who underwent radical cystectomy

OBJECTIVES: To determine the value of the loss of expression of E-cadherin and cadherin associated molecules as useful markers for both prognosis and chemosensitivity in bladder cancer patients who have undergone radical cystectomy. PATIENTS AND METHODS: In 55 paraffin embedded specimens of radical cystectomy at our hospital from 1982 to 2000, the expression of E-cadherin, alpha-, beta- and gamma-catenin was examined by immunohistochemical staining. To evaluate the prognostic significance of these molecules, Kaplan-Meier survival curves were constructed and a statistical analysis was calculated by a log-rank test. A multivariate test (tumor stage, tumor grade, lymph node metastasis, configuration, the expression of E-cadherin, alpha-, beta- and gamma-catenin) was performed to detect prognostic markers. RESULTS: Normal expression was found in 33 cases (60.0%) for E-cadherin, 29 (52.7%) for alpha-catenin, 31 cases (56.4%) for beta-catenin, and 31 cases (56.4%) for gamma-catenin. The expression patterns for E-cadherin, alpha-, beta- and gamma-catenin were significantly correlated with each other (P < 0.01). Survival analysis showed a significant difference between normal and aberrant expression in each staining. A multivariate analysis revealed that the expression of alpha- catenin was an independent prognostic factor (P = 0.0191). In 23 patients that received adjuvant chemotherapy, there was a significant difference in survival between the normal and aberrant expression of alpha-catenin, but not other molecules. CONCLUSION: Alpha-catenin may not only be a good prognostic marker, but also one of key molecules that determine the chemosensitivities in patients with invasive bladder cancer.