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Biomedical subjects

C R Lee

Publications and source records attributed to C R Lee.

84 records · Page 5Linked to original sources

The relationship of plasma to erythrocyte lithium levels in patients taking lithium carbonate.

Plasma and erythrocyte lithium levels have been determined repeatedly in twelve patients taking lithium carbonate for affective disorders. In any individual the plot of the plasma lithium level against erythrocyte/plasma ratio is linear, but the ratio can either increase or decrease with increasing plasma lithium concentration. Erythrocyte/plasma ratio is an unsound basis for comparing individual responses to lithium.

Adult↗

New derivatives of argininosuccinic acid in the urine of a patient with argininosuccinicaciduria.

The urine of a patient with argininosuccinicaciduria contains several previously undescribed compounds that can be derived chemically from argininosuccinic anhydride (I). One of the major compounds is 8-carboxy-2-carboxymethyl-3-oxo-2,3,5,6,7,8-hexa-hydro-1H-imidazo [1,2-a][1,3]diazepine, which exists as two diastereoisomers that are readily interconvertible at pH5. The corresponding ring-opened monocyclic diazepines are also present, as well as traces of the isomeric hexahydroimidazodiazepines that are formally related to argininosuccinic anhydride (II). The formation and stereochemistry of these compounds are discussed.

Amino Acid Metabolism, Inborn Errors↗

Outgrowth of chondrocytes from human articular cartilage explants and expression of alpha-smooth muscle actin.

The objectives of this study were to investigate the effect of various enzymatic treatments on the outgrowth of chondrocytes from explants of adult human articular cartilage and the expression of a specific contractile protein isoform, alpha-smooth muscle actin, known to facilitate wound closure in other connective tissues. Explants of articular cartilage were prepared from specimens obtained from patients undergoing total joint arthroplasty. The time to cell outgrowth in vitro was determined and the expression of alpha-smooth muscle actin shown by immunohistochemistry. Treatment of the explants with collagenase for 15 minutes reduced the time to outgrowth from more than 30 days to 3 days. Hyaluronidase, chondroitinase ABC, and trypsin applied for the 15-minute period had no effect on the time to cell outgrowth when compared with untreated controls. Pretreatment with hyaluronidase prior to collagenase reduced the time to outgrowth. A notable finding of this study was that the majority of chondrocytes in the adult human articular cartilage specimens and virtually all of the outgrowing cells contained alpha-smooth muscle actin. We conclude that human articular chondrocytes have the capability to migrate through enzymatically degraded matrix and express a contractile actin isoform. Collagenase treatment reduces the time required for cell outgrowth.

Actins↗

CYP2C9 genotype as a predictor of drug disposition in humans.

Discovery of genetic polymorphisms in CYP2C9 has stimulated numerous in vitro and in vivo studies evaluating the influence of CYP2C9 genotype on metabolic activity and drug disposition. CYP2C9*2 (Arg144Cys) and *3 (Ile359Leu) have been the most widely studied alleles. They are present in approximately 10-15% and 5-10% of white populations, respectively, and are even less frequent in black and Asian populations. The CYP2C9*2 and *3 alleles have been consistently associated with lower intrinsic clearance compared with CYP2C9*1 in vitro; however, the magnitude of these differences appears to be highly substrate-specific. In addition, multiple human studies have demonstrated significant associations between CYP2C9 genotype and the disposition of substrates such as warfarin, phenytoin and various sulfonylureas, angiotensin II receptor blockers and non-steroidal antiinflammatory agents. Individuals carrying the CYP2C9*2 and *3 alleles also have lower warfarin and phenytoin daily dose requirements, and appear more susceptible to adverse events during the initiation of therapy. Collectively, these findings suggest that CYP2C9 genotype-guided dosing may be clinically useful and warrants prospective investigation.

Aryl Hydrocarbon Hydroxylases↗