The importance of calcium ions forin vitro malignant hyperthermia testing

Intracellular Ca++ levels in skeletal muscle are elevated during the in vitro contracture response of muscle from subjects with malignant hyperthermia. The role of Ca++ in the bathing medium and the consequences of substitution of Sr++ for Ca++ in the response to agents associated with malignant hyperthermia were examined. When Ca++ was omitted from the bathing medium the contractures induced in human vastus lateralis by halothane (three per cent) or succinylcholine (50 mM) were reduced by 80 and 100 per cent, respectively, while contractures induced by caffeine (8 mM) were only reduced by 50 per cent. Substitution of Ca++ by another divalent cation, Sr++, completely restored contractures induced by caffeine, but only partially restored contractures induced by halothane or succinylcholine (to 50 and 30 per cent of Ca(++)-containing medium, respectively). Mepacrine (10 microM) was effective in antagonizing contractures by caffeine, whereas verapamil and nifedipine (10 microM) were not. These results support an essential role for extracellular Ca++ not fulfilled by Sr++ in contracture induction by halothane and succinylcholine, but not by caffeine.     

Discovery of potent and selective inhibitors of procollagen C-proteinase for the treatment of fibrotic disorders

Introduction   Fibrosis is a component of many tissue pathologies leading to loss of normal tissue function, primarily due to excessive collagen deposition. Collagen is deposited following cleavage of the C- and N- terminal peptides from the pro-collagen molecule. The cleavage of the globular C-peptide by PCP reduces solubility of the fibrillar collagen molecule, resulting in deposition of insoluble collagen. Increased insoluble collagen deposition is a feature of all organ fibroses, with inhibition of this process, a key potential anti-fibrotic mechanism. The aim of this work was to discover potent and selective PCP inhibitors as experimental, topically applied, anti-fibrotic drugs for clinical evaluation.
Materials and methods   PCP was cloned from human osteosarcoma cells and enzymatic activity demonstrated using a PCP-specific peptide cleavage assay. Activities were confirmed by measuring cleavage of [³H]C-peptide from type-I pro-collagen. A cell-based fibroplasias model was employed to demonstrate compound efficacy using collagen deposition, liberated C-peptide and histological endpoints. The activities of PCP inhibitors in fibroblast and epithelial in vitro cell proliferation and migration assays, and selectivity vs. a panel of MMPs were also determined.
Discussion   In summary, we have identified and characterized potent and selective inhibitors of PCP for progression to clinical studies for investigation as a treatment paradigm for fibrotic disease.  

  Results     

7.

Renal Stones          下载免费PDF全文

Ilyas Arshad  KA Shar-Baloch 《Annals of the Royal College of Surgeons of England》2007,89(3):326

     

8.

A new anthropometric scale for discrimination between sexes.     

D Z Loesch  M LaFranchi  R Huggins 《Annals of human biology》1992,19(2):177-184

Sexual dimorphism with respect to body size and shape has been analysed by means of discriminant function. An anthropometric score has been derived from 111 adult normal males and 108 females, based on 11 anthropometric and three dermatoglyphic variables. The score represents the range of quantified physical phenotypes of 'maleness' and 'femaleness'. Complete separation between the distributions of this score in either sex has been achieved. Predominantly, application of the anthropometric score can be in assessing a relationship between the anthropometric status of 'maleness' or 'femaleness', and cytogenetic or submicroscopic anomalies of sex chromosomes, and in studies of normal inter- and intra-population variation in sexual dimorphism.     

9.

Colorectal cancer: diagnostic potential of CT measurements of hepatic perfusion and implications for contrast enhancement protocols   总被引：28，自引：0，他引：28  

Leggett  DA; Kelley  BB; Bunce  IH; Miles  KA 《Radiology》1997,205(3):716

     

10.

Creation of transjugular intrahepatic portosystemic shunts with the wallstent endoprosthesis: results in 100 patients   总被引：17，自引：0，他引：17  

LaBerge  JM; Ring  EJ; Gordon  RL; Lake  JR; Doherty  MM; Somberg  KA; Roberts  JP; Ascher  NL 《Radiology》1993,187(2):413

     

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A new anthropometric scale for discrimination between sexes.

Sexual dimorphism with respect to body size and shape has been analysed by means of discriminant function. An anthropometric score has been derived from 111 adult normal males and 108 females, based on 11 anthropometric and three dermatoglyphic variables. The score represents the range of quantified physical phenotypes of 'maleness' and 'femaleness'. Complete separation between the distributions of this score in either sex has been achieved. Predominantly, application of the anthropometric score can be in assessing a relationship between the anthropometric status of 'maleness' or 'femaleness', and cytogenetic or submicroscopic anomalies of sex chromosomes, and in studies of normal inter- and intra-population variation in sexual dimorphism.