C2H2-171 : A novel human cDNA representing a developmentally regulated poz domain/zinc finger protein preferentially expressed in brain

We describe a novel human zinc finger cNDA, C2H2-171. This cDNA represents an mRNA which encodes a protein of 484 amino acids and a calculated molecular weight of 54 kD. Four zinc finger-like domains are found in the C-terminal end of the protein. At the N-terminus, C2H2-171 contains a POZ/tramtrack-like domain similar to that found in the tumor associated zinc finger proteins LAZ-3/BCL-6 and PLZ-F, as well as in non-zinc finger proteins. C2H2-171 RNA is preferentially expressed in the brain, and increases during the course of murine development, with maximal expression in the adult. C2H2-171 RNA is differentially expressed in brain regions, with the highest level of expression in the cerebellum. C2H2-171 RNA was expressed at high levels in primary cerebellar granule cell neurons compared to astrocytes. The gene encoding C2H2-171 is highly conserved in vertebrates, and maps to the terminus of human chromosome 1 (1q44-ter). This chromosomal location is associated with a number of cytogenetic aberrations including those involving brain developmental anomalies and tumorigenesis. These data suggest that C2H2-171 may play an important role in vertebrate brain development and function.     

A new shape for an old function: lasting effect of a physiologic surgical restoration of the left ventricle

Background  

Long-term morphofunctional outcome may vary widely in surgical anterior left ventricular wall restoration, suggesting variability in post-surgical remodeling similar to that observed following acute myocardial infarction. The aim of this pilot study was to demonstrate that surgical restoration obtained with a particular shape of endoventricular patch leads to steady morphofunctional ventricular improvement when geometry, volume and residual akinesia can be restored as normal as possible.     

Idarubicin metabolism and pharmacokinetics after intravenous and oral administration in cancer patients: a crossover study

The pharmacokinetics and metabolism of 4-demethoxydaunorubicin (idarubicin, IDA) were studied in 21 patients with advanced cancer after i.v. (12 mg/m2) and oral (30-35 mg/m2) treatment according to a balanced crossover design. Patients were divided into four groups: subjects who showed normal liver and kidney function (group N), those who presented with normal kidney function and liver metastases (group L), those with kidney dysfunction (creatinine clearance, less than or equal to 60 l/h; group R), and those with both liver and kidney dysfunction (group LR). Five patients showed variations in liver or kidney function after the first treatment and were considered to be nonevaluable for the crossover study but evaluable for the liver/kidney function study; some of them appeared in different groups for the i.v. as opposed to p.o. treatments. After i.v. administration, IDA plasma levels followed a triphasic decay pattern. The main metabolite observed in all patients was the 13C-reduced compound (IDAol), which attained plasma levels 2-12 times higher than those of the parent compound. IDA pharmacokinetics was not dependent on the presence of liver metastases but was related to the integrity of kidney function. Analysis of variance indicated a significant correlation between IDA plasma clearance and creatinine clearance; it was also found that IDA plasma clearance was lower in patients whose creatinine clearance was less than 60 ml/min [group N, 122.8 +/- 44.0 l/h; group L, 104.4 +/- 27.7 l/h (P = 0.58) vs group R, 83.4 +/- 18.3 l/h (P = 0.037)]. The IDAol terminal half-life and mean residence time (MRT) were significantly increased in patients with impaired kidney function [MRT: group N, 63.6 +/- 10.8 h; group L, 69.9 +/- 10.2 h (P = 0.27) vs group R, 83.2 +/- 10.9 h (P = 0.025) and t1/2 gamma: group N, 41.3 +/- 10.1 h; group L, 47.0 +/- 7.4 h (P = 0.31) vs group R, 55.8 +/- 8.2 h (P = 0.025)]. After oral treatment, drug absorption occurred during in the first 2-4 h after IDA administration; a biphasic decay pattern was observed thereafter. The main metabolite observed in all patients was again IDAol. The AUC of IDAol was greater after oral administration than after i.v. treatment in proportion to the AUC of IDA (i.v.: AUC-IDAol/AUC-IDA, 2.4-18.9; p.o.: AUC-IDAol/AUC-IDA, 4.1-21.4). Following oral dosing, a substantial amount of 4-demethoxydaunomycinone (AG1) was found in 11/21 patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Serum levels of growth hormone-binding protein and insulin-like growth factor-I during puberty.

OBJECTIVE: The aim was to investigate the effect of pubertal development on serum levels of growth hormone binding protein (GHBP) and IGF-I, and to study the relationship between GHBP levels and height standard deviation score (SDS), nutritional state and IGF-I levels. DESIGN AND PATIENTS: The investigation was performed on serum samples from 72 healthy adolescents of different pubertal stage. Results were compared to those obtained in 46 prepubertal children. MEASUREMENTS: Serum levels of GHBP were measured by HPLC gel filtration and IGF-I levels were measured by RIA after acid-ethanol extraction. RESULTS: No effect of pubertal stage on serum levels of GHBP was found. A positive relationship was found between serum levels of GHBP and height SDS (r = 0.38; P < 0.005) and weight expressed as percentage of median weight for height age (r = 0.46; P < 0.0005). Serum levels of IGF-I increased during puberty and were not correlated with height SDS or weight for height age. In pubertal subjects, no relationship existed between serum levels of GHBP and IGF-I. In prepubertal subjects, however, a significantly positive relationship between GHBP and IGF-I levels (r = 0.66; P < 0.0005) was found. CONCLUSIONS: Pubertal development does not seem to influence serum levels of GHBP. Height SDS and nutritional state are related to the concentration of GHBP. Before puberty, the level of GHBP is positively related to IGF-I levels; during puberty, however, the increase in serum IGF-I levels is not accompanied by changes in the amount of circulating GHBP.     

Torsional properties of the Canal Master instrument.

The torsional properties of a new type of endodontic hand instrument, the Canal Master, were compared with conventional machined K-type endodontic files. Sizes 20 through 50 were tested in clockwise (CW) and counterclockwise (CCW) directions. Canal Master instruments exhibited significantly less torque at yield and at failure in both the CW and CCW directions. Rotation at failure was significantly greater for the Canal Master instruments in both CW and CCW directions. There was no significant difference in either torque or the amount of rotation for the Canal Master instruments when comparing CW versus CCW rotation. There was no clinically visible evidence of deformation of the Canal Master instruments prior to torsional failure.