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Epidermal growth factor receptor (EGFR) in the prognosis of bladder carcinoma. Experience of 5 years
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Sukhwinder S Lakhman Debashis Ghosh Javier G Blanco 《Drug metabolism and disposition》2005,33(2):254-257
Human carbonyl reductase (CBR) activity accounts for a significant fraction of the metabolism of endogenous and xenobiotic carbonyl compounds. It is possible that genetic polymorphisms in CBR1 and CBR3 are key for the wide interindividual variability in the disposition of CBR drug substrates. We pinpointed a single nucleotide polymorphism in CBR3 (CBR3 V244M) that encodes for a V244 to M244 change. Blacks showed a higher frequency of the M244 allele (q = 0.51, n = 49) than did whites (q = 0.31, n = 70; p = 0.003). In addition, DNA variation panels from 10 ethnic groups presented a wide range of CBR3 V244M genotype distributions. Kinetic experiments with the recombinant CBR3 protein variants and menadione revealed that CBR3 M244 has significantly higher V(max) than does CBR3 V244 (V(max) CBR3 M244 = 40.6 +/- 1.3 micromol/min x mg versus V(max) CBR3 V244 = 19.6 +/- 2.0 micromol/min x mg, p = 0.002). In contrast, both isoforms presented similar K(m) values (K(m) CBR3 M244 = 22.9 +/- 2.9 microM versus K(m) CBR3 V244 = 24.6 +/- 3.2 microM, p = 0.43). Assays with NADP(H) demonstrated a higher V(maxNADP(H)) (1.6-fold) and increased catalytic efficiency (V(maxNADP(H))/K(mNADP(H))) for CBR3 M244 compared with CBR3 V244 (p = 0.013). Comparative three-dimensional analyses based on the structure of the homologous porcine carbonyl reductase suggested that the V244M substitution is positioned in a region critical for interactions with the NADP(H) cofactor. These studies demonstrate that the common CBR3 V244M polymorphism encodes for CBR3 isoforms with distinctive enzymatic properties. 相似文献
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Lleonart R Riego E Saínz de la Peña MV Bacallao K Amaro F Santiesteban M Blanco M Currenti H Puentes A Rolo F Herrera L de la Fuente J 《International journal of legal medicine》2000,113(2):98-101
We report the positive identification of several members of the guerrillas led by Ernesto “Che” Guevara on the 1960 s in
Bolivia by means of DNA fingerprinting. Successful DNA typing of both short tandem repeat loci and the hypervariable region
of the human mitochondrial DNA was achieved after extracting total DNA from bones obtained from two burial sites. Given the
size of the Cuban database for the STR allele frequencies, a conservative approach was followed to estimate the statistical
significance of the genetic evidence. The estimated probabilities of paternity for the two cases in which the paternity logic
was applied were higher than 99%. One case was analyzed using mitochondrial DNA and could not be excluded from the identity
proposed by the forensic anthropology team. A fourth case was identified by exclusion, on the basis of the positive identification
of the other remains, the historical and other anthropological evidence.
Received: 19 January 1999 / Received in revised form: 15 April 1999 相似文献
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A. Simoneau N. Foussard L. Blanco F. Domenge M. Monlun P. Poupon V. Rigalleau 《Diabetes & metabolism》2021,47(1):101121
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Immunomodulatory effects of bone marrow versus adipose tissue‐derived mesenchymal stromal cells on NK cells: implications in the transplantation setting
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