KinMutBase, a database of human disease-causing protein kinase mutations

KinMutBase (http://www.uta.fi/laitokset/imt/KinMut Base.html) is a registry of mutations in human protein kinases related to disorders. Kinases are essential cellular signalling molecules, in which mutations can lead into diseases including, e.g., immunodeficiencies, cancers and endocrine disorders. The first release of KinMutBase contains information for nine protein tyrosine kinases. There are altogether 170 entries representing 273 families and 403 patients. Mutations appear both in conserved hallmark residues of the kinases as well as in non-homologous sites. The KinMutBase WWW pages provide plenty of information, namely mutation statistics and display, clickable sequences with mutations, restriction enzyme patterns and online submission.     

Adaptive Cluster Sampling: Estimating Density of Spatially Autocorrelated Larvae of the Sea Lamprey with Improved Precision

Adaptive cluster sampling (ACS) provides researchers with an alternative technique to estimate the abundance of rare or spatially clustered organisms, but its application in field investigations has been limited to relatively few studies. We used ACS to estimate parameters of a spatially autocorrelated population of larval sea lampreys, Petromyzon marinus, in Wilmot Creek, a Lake Ontario tributary. When compared with simple random sampling (SRS), ACS significantly increased catch per sample as well as the percentage of samples that contained larvae. Although ASC-generated samples are spatially biased, the use of established formulae enabled us to calculate unbiased estimators of mean larval density and variance. With ACS, variance was reduced, improving the precision around estimates of mean density, however; increased precision came at the price of greater sampling effort. When variance was adjusted for effort, ASC provided equal or greater efficiency than SRS in 33% of sampling events, with no apparent site or seasonal bias. Based on the knowledge that larval sea lampreys are spatially aggregated, we anticipated that ACS would result in higher precision for a greater proportion of sampling events. Nonetheless, we consider ACS to be a useful technique for evaluating larval sea lamprey populations and anticipate increased application for investigating other spatially over-dispersed species.     

Management of hysteroscopic surgery complications

Hysteroscopic surgery is considered a safe, routine gynecologic procedure performed in the OR and in office settings. Complications are rare; however, when complications do occur they can be severe and rapid. The surgical team members must understand the significance of patient monitoring and proper equipment operation to ensure positive patient outcomes. This article discusses complications from intravasation of various distending media used during hysteroscopy and the complication of hyponatremia. A physiologic approach to these problems enhances awareness of the significance of patient monitoring during hysteroscopic procedures.     

Stable association of PYK2 and p130(Cas) in osteoclasts and their co-localization in the sealing zone

Bone resorption is initiated by osteoclast attachment to the mineralized matrix, cytoskeletal reorganization, cellular polarization, and the formation of the sealing zone. The present study examines the interaction between PYK2 and p130(Cas) (Crk-associated substrate), suggested to be part of the signaling pathway initiated by osteoclast adhesion. Using murine osteoclast-like cells (OCLs) and their mononuclear precursors (pOCs), generated in a co-culture of bone marrow and osteoblastic MB1.8 cells, we show that: 1) p130(Cas) is tyrosine-phosphorylated upon adhesion of pOCs to vitronectin or ligation of beta3 integrins; 2) p130(Cas) colocalizes with PYK2 and the cytoskeletal proteins F-actin, vinculin, and paxillin in the podosomal-rich ring-like structures of OCLs plated on glass and in the sealing zone in actively resorbing OCLs on bone; 3) p130(Cas) and PYK2 form a stable complex in pOCs, independent of tyrosine phosphorylation of either molecule, and this complex is present in Src (-/-) OCLs, in which neither protein is phosphorylated or associated with the osteoclast adhesion structure; 4) the association of p130(Cas) and PYK2 is mediated by the SH3 domain of p130(Cas) and the C-terminal domain of PYK2. These findings suggest that p130(Cas) and its association with PYK2 may play an important role in the adhesion-dependent signaling that leads to cytoskeletal reorganization and formation of the sealing zone during osteoclast activation.     

Sydenham Chorea: magnetic resonance imaging reveals permanent basal ganglia injury

We report the case of a 26-year-old man with diffuse esophageal leiomyomatosis involving the trachea. The tumor was resected by total esophagectomy and partial resection of the trachea and the left main bronchus. The tracheobronchial defect was repaired with a free forearm skin graft with satisfactory outcome. This approach offers good long-term prospects.     

The coenzyme A-synthesizing protein complex and its proposed role in CoA biosynthesis in bakers'' yeast

An improved procedure is described for the recovery and purification of the coenzyme A-synthesizing protein complex (CoA-SPC) of Saccharomyces cerevisiae (bakers' yeast). The molecular mass of the CoA-SPC, determined prior to and following its purification, is estimated by Sephacryl S-300 size exclusion chromatography to be between 375,000-400,000. Two previously unreported catalytic activities attributed to CoA-SPC have been identified. One of these is CoA-hydrolase activity which catalyzes the hydrolysis of CoA to form 3',5'-ADP and 4'-phosphopantetheine, and the other is dephospho-CoA-pyrophosphorylase activity which catalyzes a reaction between 4'-phosphopantetheine and ATP to form dephospho-CoA. The dephospho-CoA then reacts with ATP, catalyzed by the dephospho-CoA-kinase, to reform CoA. This sequence of reactions, referred to as the CoA/4'-phosphopantetheine cycle, provides a mechanism by which the 4'-phosphopantetheine can be recycled to form CoA. Each turn of the cycle utilizes two mol of ATP and produces one mol of ADP, one mol of PPi, and one mol of 3',5'-ADP. Other than the hydrolysis of CoA by CoA-SPC, the 4'-phosphopantetheine for the cycle apparently could be supplied by alternate sources. One alternate source may be the conventional pathway of CoA biosynthesis. Intact CoA-SPC has been separated into two segments. One segment is designated apo-CoA-SPC and the other segment segment is referred to as the 10,000-15,000 M(r) subunit. The 5'-ADP-4'-pantothenic acid-synthetase, 5'-ADP-4'-pantothenylcysteine-synthetase, 5'-ADP-4'-pantothenylcysteine-decarboxylase, and CoA-hydrolase activities reside in the apo-CoA-SPC segment of CoA-SPC. Whereas the dephospho-CoA-kinase and the dephospho-CoA-pyrophosphorylase activities reside in the 10,000-15,000 M(r) subunit. Thus, the 10,000-15,000 M(r) subunit mimics the bifunctional enzyme complex that catalyzes the final two steps in the conventional pathway of CoA biosynthesis.     

The Kock pouch urinary reservoir

The use of detubularized ileum for the Kock pouch produced a low pressure, high capacity system superior to large bowel segments that provided excellent continence and protection of the upper urinary tracts. The early enthusiasm was tempered, however, by the technically demanding aspects of the construction of the nipple valves, the early and late complications, and occasional catheterization problems. With simple modifications in the fixation of the intussuscepted nipples, limiting use of staples and mesh collars, and tapering of the stoma, much of those problems have been resolved. The nipple valve is reliable and superior to the tunneled implant for the dilated ureter. With more widespread indications for continent neobladders, the hemi-Kock reservoir remains one of the most dependable and stable neobladders.