The role of breast cancer resistance protein (BCRP), an efflux ABC transporter, in the pharmacokinetics of substrate drugs in humans is unknown. We investigated the impact of genetic polymorphisms of ABCG2 (421C>A) and NAT2 on the pharmacokinetics of sulfasalazine (SASP), a dual substrate, in 37 healthy volunteers, taking 2,000 mg of conventional SASP tablets. In ABCG2, SASP AUC(0-48) of C/C, C/A, and A/A subjects was 171 +/- 85, 330 +/- 194, and 592 +/- 275 microg h/ml, respectively, with significant differences among groups. In contrast, AUC(0-48) of sulfapyridine (SP) tended to be lower in subjects with the ABCG2-A allele as homozygosity. In NAT2, AUC(AcSP)/AUC(SP) was significantly higher in rapid than in intermediate and slow acetylator (SA) genotypes. We successfully described the pharmacokinetics of SASP, SP, and N -acetylsulfapyridine (AcSP) simultaneously by nonlinear mixed-effects modeling (NONMEM) analysis with regard to both gene polymorphisms. The data indicate that SASP is a candidate probe of BCRP, particularly in its role in intestinal absorption.
Nine trees of Cryptomeria japonica from six elite tree clones with a broad range of heartwood colors were selected. The profiles of pit aspiration percentage (ASP) of earlywood and latewood from pith to bark for green and air-dry conditions were determined to study the relationship between heartwood color and pit aspiration. Confocal laser scanning microscopy (CLSM) observations showed that the ASP of earlywood was low in sapwood and high in heartwood in the green condition. Pit aspiration increased in intermediate wood when compared with sapwood. On the other hand, latewood pits did not aspirate during heartwood formation. Comparing the air-dry condition with the green condition, sapwood pits aspirated during drying in both earlywood and latewood; however, there was no significant difference in pit aspiration of heartwood. There was no significant difference between samples with red and black heartwoods for ASP. The difference in ASP between individual trees was larger than that by heartwood color. The general advantage of CLSM over light microscopy is that serial optical sections along the Z axis can be obtained for any moisture condition, without the need for thin sectioning or embedding.
ABSTRACT:In Pinus , Subgenus Pinus 16 species were investigated on their somatic chromosomes by a fluorescent banding technique using chromomycin A 3 (CMA) and 4',6-diamidino-2-phenylindole (DAPI). The chromosome number of 2n=24 was commonly counted in all the species studied. Their karyotypes were composed of many long metacentric chromosomes and a few short submetacentric chromosomes, and two karyotypes were recognized in respect to number of short chromosomes in the subgenus. CMA-bands appeared at an interstitial and/or proximal region of chromosomes and DAPI-band did at a proximal region. Thin DAPI-bands appeared at interstitial regions and DAPI-dots appeared at a centromeric region in most chromosomes. In a chromosome complement each homologous chromosome was identified on the base of its shape and fluorescent banding pattern. The typical banding patterns were compared among the species studied. Many interstitial CMA-bands at the secondary constrictions appeared on many metacentric chromosomes. Proximal fluorescent bands varied in fluorescent nature and number and divided into several groups. Section Pinus short three chromosome pairs were two or three patterns of fluorescent banding. The section Trifolae species had many proximal DAPI-bands and less proximal CMA-bands than section Pinus. The shortest chromosome had proximal bands indicating two groups on the kinds of fluorescent band.
We investigated the allele and genotype distribution of a polymorphism of the tumor necrosis factor (TNF) B gene and the frequency of HLA-DR9 in 49 patients with Palmoplantar pustulosis (PPP) and 51 healthy controls. We found that the frequency of TNFB2 in the PPP patients was significantly higher than that in the controls. Furthermore, the DR9-TNFB2 haplotype was significantly more frequent in the PPP patients (P=0.0045). These results suggest that TNFB2 may confer susceptibility to PPP.
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