cDNA Cloning, Tissue Distribution and Chromosomal Localization of the Human ID4 Gene

A cDNA encoding the human Id4 protein has been isolated froman astrocytoma library. The predicted protein product shares98% identity with the mouse Id4 protein and is markedly differentfrom that already reported. By FISH analysis, the human ID4gene was more precisely mapped to chromosome 6p22.3-p23. Northernblot analysis showed that ID4 is mainly expressed in thyroid,brain and fetal tissue and in some nervous system tumor celllines.     

Effects of metal cations and other chemicals upon the in vitro activity of two enzymes in the blood plasma of the white sucker, Catostomus commersoni (Lacépède)

Relative changes in the activity of glutamic oxalacetic transaminase (GOT, l-aspartate-2-oxoglutarate aminotransferase) and lactic dehydrogenase (LDH, l-lactate-NAD oxidoreductase) in blood plasma from white suckers were determined after incubation with 49 compounds, principally inorganic chlorides, at concentrations of the ions up to 2 mg/ml in the reaction mixture. A sequence of inhibitory effect was arranged for each enzyme. Dose-response curves were qualitatively similar for most of the chemicals. GOT was most sensitive to silver and mercury, and LDH to palladium and mercury. Both enzymes are highly inhibited by metals which are highly toxic to aquatic animals. Correlations were studied between the inhibitory effect and certain physicochemical properties of chemicals, the best being found between the inhibition of GOT and the equilibrium constants of metal sulfides.     

Probasin Promoter�Cdriven Expression of ID1 Is not Sufficient for Carcinogenesis in Rodent Prostate

Inhibitor of DNA-binding-1 (ID1) negatively regulates cell differentiation and senescence, and enhances cellular proliferation and angiogenesis. Elevated levels of ID1 have been found in a variety of cancers, including prostate cancer, but whether ID1 has a tumourigenic role remains to be established. We established heterozygous and homozygous ID1-transgenic mouse lines driven by the prostate-specific probasin promoter (−426 to +28 bp). Although elevated levels of ID1 were confirmed by RT-PCR, immunohistochemistry, and Western blot analysis, there were no morphological changes identified in the prostate of transgenic mice at 26 and 52 weeks. Thus, overexpression of ID1 alone is not sufficient to drive neoplastic change in mouse prostate. (J Histochem Cytochem 57:599–604, 2009)     

Acute Taxol nephrotoxicity: Histological and ultrastructural studies of mice kidney parenchyma

Taxol is a microtubule inhibitor drug widely used in treatment of many types of cancer. Nephrotoxicity is the most hazardous effect complicating chemotherapy in general and kidney functions must be monitored early during any chemotherapeutic course. The main objective of the present study was to investigate the effect of acute Taxol nephrotoxicity in mice. In the present study Taxol at different doses; MD, ID and MTD (0.6, 1.15 and 1.7 mg/kg), respectively, was given by intra-peritoneal route to 54 adult male mice with an average body weight of 20–25 g. Kidney samples was taken 6, 24, 48 h following administration, fixed in 10% neutral buffered formalin, paraffin sections 5 μm thick were stained by haematoxylin and eosin and PAS and then examined for histological changes. Samples from animals treated by the maximum dose (MTD = 1.7 mg/kg) for 48 h were fixed in 3% gluteraldehyde in phosphate buffer (pH 7.4) and processed for transmission electron microscope. Taxol given for short duration was found to produce marked degenerative changes in kidney parenchyma even in minimum tolerated dose (MD = 0.6 mg/kg). Individual variations were observed regarding the degree of nephrotoxicity. There was marked loss of renal tubules epithelial lining, damage of brush border and formation of hyaline casts within the damaged tubules. The alterations were in the form of both necrotic and apoptotic changes in the kidney tubules. Focal atrophy of glomerular tufts was also observed. Vascular congestion and degenerative changes in renal blood vessels were occasionally evident in some samples. Ultrastructure study revealed damage of glomerular membrane. Proximal tubule showed loss of basal infoldings, damage of brush border, mitochondrial degeneration and nuclear changes. Distal tubules also showed demarked degenerative changes. Increased frequency of micronuclei proved that Taxol had genotoxic effects in mice bone marrow cells. In conclusion Taxol had nephrotoxic effect on mice kidney that must be considered during its use as a chemotherapeutic agent in human.     

Rhenium and technetium complexes with anionic or neutral scorpionates: An overview of their relevance in biomedical applications

This article reviews the chemistry of Re and Tc complexes anchored by anionic and neutral scorpionates with potential relevance in the field of biomedical applications, particularly in radiopharmaceutical research. For poly(azolyl)borates, the revised work focuses mainly on poly(mercaptoimidazolyl)borate tricarbonyl M(I) complexes, while for tris(pyrazolyl)methanes the revision includes M(VII) trioxo- and M(I) tricarbonyl complexes. A comprehensive update of structural, chemical, radiochemical and biological aspects relevant for the use of these compounds in the design of radiopharmaceuticals is presented and discussed.     

Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity

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Comparison of different protein precipitation and solid‐phase extraction protocols for the study of the catabolism of peptide drugs by LC‐HRMS

LC‐HRMS‐based identification of the products of peptide catabolism is the key to drive the design of more stable compounds. Because the catabolite of a given peptide can be very different from the parent compound and from other catabolites in terms of physicochemical properties, it can be challenging to develop an analytical method that allows recovery and detection of the parent and all parent‐related catabolites. The aim of this study was to investigate how the recovery and the matrix effect of peptidic drugs and their catabolites are affected by different protein precipitation (PP) and solid‐phase extraction (SPE) protocols. To this purpose, four model peptides representative of different classes (somatostatin, GLP‐2, human insulin and liraglutide) were digested with trypsin and chymotrypsin to simulate proteolytic catabolism. The resulting mixtures of the parent peptides and their proteolytic products covering a wide range of relative hydrophobicity (H_R) and isoelectric points (pI) were spiked in human plasma and underwent different PP and SPE protocols. Recovery and matrix effect were measured for each peptide and its catabolites. PP with three volumes of ACN or EtOH yielded the highest overall recoveries (more than 50% for the four parent peptides and all their catabolites) among all the tested PP and SPE protocols. Mixed‐mode anion exchange (MAX) was the only SPE sorbent among the five tested that allowed to extract all the peptides with recoveries more than 20%. Matrix effect was generally lower with SPE. Overall, it was observed that peptides with either high hydrophilicity (e.g., somatostatin catabolites) or hydrophobicity (GLP‐2 and lipidated liraglutide catabolites) had a much narrower choice of PP solvent or SPE protocol. Simulation of catabolism using recombinant enzymes together with in silico calculation of the H_R and the pI of potential proteolysis products is recommended to select the optimal extraction conditions for the study of peptide catabolism.     

TCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions

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A MYT1L syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation

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