Random high throughput sequencing of a human osteoclast cDNA library was employed to identify novel osteoclast-expressed genes. Of the 5475 ESTs obtained, approximately 4% encoded cathepsin K, a novel cysteine protease homologous to cathepsins S and L; ESTs for other cathepsins were rare. In addition, ESTs for cathepsin K were absent or at low frequency in cDNA libraries from numerous other tissues and cells. In situ hybridization in osteoclastoma and osteophyte confirmed that cathepsin K mRNA was highly expressed selectively in osteoclasts; cathepsins S, L, and B were not detectable. Cathepsin K was not detected by in situ hybridization in a panel of other tissues. Western blot of human osteoclastoma or fetal rat humerus demonstrated bands of 38 and 27 kDa, consistent with sizes predicted for pro-and mature cathepsin K. Immunolocalization in osteoclastoma and osteophyte showed intense punctate staining of cathepsin K exclusively in osteoclasts, with a polar distribution that was more intense at the bone surface. The abundant expression of cathepsin K selectively in osteoclasts strongly suggests that it plays a specialized role in bone resorption. Furthermore, the data suggest that random sequencing of ESTs from cDNA libraries is a valuable approach for identifying novel cell-selective genes.
Pl(A2)-positive platelets displayed a lower threshold for activation, and platelets heterozygous for Pl(A) alleles showed increased sensitivity to 2 antiplatelet drugs. These in vitro platelet studies may have relevance for in vivo thrombotic conditions.
Rat and human pancreatic duct cells have small-conductance Cl- channels in their apical plasma membranes. These channels are regulated by secretin and adenosine 3',5'-cyclic monophosphate and may function in parallel with Cl(-)-HCO3- exchangers to allow HCO3- secretion from the duct cell. Using the patch-clamp technique, we have now determined the anion permeability sequence of the channel as NO3- greater than Br- approximately I- approximately Cl- much greater than HCO3- much greater than gluconate. From this we conclude 1) that anion permeation involves a weak interaction with charged sites inside the channel pore, 2) that because of the low HCO3-/Cl- permeability ratio it is unlikely that significant amounts of HCO3- could be secreted directly via the channel, and 3) that channel permeability may determine the anion selectivity of secretion. We also show that 5-nitro-2-(3-phenylpropylamino)benzoic acid blocks the small-conductance Cl- channel, whereas 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid has no effect.
This paper reviews the literature on psychological assessment report writing and describes a study of elementary school teachers' (n ϭ 104) ratings of three alternate report styles. Results indicated that teachers assigned higher ratings to reports in which the results were organized by themes rather than in a test-by-test format. Teachers rated the report style with a lowered reading grade level as being the most teacher-friendly. Across all three-report styles, 53% of teachers generated one or more appropriate intervention ideas based on the assessment data. The discussion describes strategies for educating professional psychologists in effective report writing and describes directions for future research.
Using the patch-clamp technique, we have identified two types of chloride channel on duct cells cultured from human fetal pancreas. The channel we observed most frequently exhibited slight outward rectification, had a conductance of 4-7 pS in cell-attached patches, and was present on the apical plasma membrane where it usually occurred in clusters. Its open-state probability was not markedly voltage dependent but was increased up to threefold by exposing duct cells to secretin (10 nM), dibutyryl cyclic AMP (1 mM), or forskolin (1 microM). The other type of chloride channel was only rarely observed. Its current-voltage relationship exhibited marked outward rectification, giving chord conductances of 19 pS for inward currents and 53 pS for outward currents. Although this channel could be activated by sustained depolarization of excised patches, once activated the open state probability was not voltage dependent. While the physiological role of these channels is not firmly established, the small-conductance channel might function in parallel with a Cl- -HCO-3 exchanger to provide a mechanism for electrogenic bicarbonate secretion from the duct cell.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.