Biomedical subjects

Jiong Zhang

Publications and source records attributed to Jiong Zhang.

24 records · Page 2Linked to original sources

PubMed2002

Common allelic variants of cytochrome P4503A4 and their prevalence in different populations.

Marked interindividual variability in expression of CYP3A4 influences the disposition of many endo- and xenobiotics, including the metabolism of steroids, environmental toxins and therapeutically useful drugs. The present study was designed to determine the genetic basis of CYP3A4 variability. We analysed DNA from 82 individuals with known CYP3A4 phenotype including 53 Caucasians and 21 African-American liver donors, seven individuals who were outliers in CYP3A4 metabolism and five individuals in a family of a poor nifedipine metabolizer. In addition, we analysed DNA from the eight person DNA Polymorphism Discovery Resource subset (Coriell Institute) and 89 individuals representing nine ethnic groups. Five non-synonymous mutations in the coding region of CYP3A4 were observed. CYP3A4*14 (T44C) in exon 1 resulted in an L15P change; CYP3A4*15 (G14387A) in exon 6 resulted in a R162Q substitution; CYP3A4*10 (G14422C) in exon 6 resulted in a D174H substitution; CYP3A4*16 (C15721G) in exon 7 resulted in a T185S amino acid substitution; and CYP3A4*12 (C22002T) in exon 11 resulted in a L373F change in the CYP3A4 protein. An additional six single nucleotide polymorphisms (SNPs) in the 5'-UTR, 13 SNPs in the introns and three SNPs in the 3'-UTR were observed. Extensive population differences were observed in the frequencies of various CYP3A4 alleles. None of the 28 CYP3A4 SNPs identified in CYP3A4 phenotyped persons (most individuals being heterozygous for any CYP3A4 variant) was associated with low hepatic CYP3A4 protein expression or low CYP3A4 activity in vivo.

Alleles↗

PubMed2002

Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism.

We recently demonstrated that a variant allele of CYP3A5 (CYP3A5*3) confers low CYP3A5 expression as a result of improper mRNA splicing. In this study, we further evaluated the regulation of CYP3A5 in liver and jejunal mucosa from white donors. For all tissues, high levels of CYP3A5 protein were strongly concordant with the presence of a wild-type allele of the CYP3A5 gene (CYP3A5*1). CYP3A5 represented greater than 50% of total CYP3A content in nearly all of the livers and jejuna that carried the CYP3A5*1 wild-type allele. Overall, CYP3A5 protein content accounted for 31% of the variability in hepatic midazolam hydroxylation activity. Improperly spliced mRNA (SV1-CYP3A5) was found only in tissues containing a CYP3A5*3 allele. Properly spliced CYP3A5 mRNA (wt-CYP3A5) was detected in all tissues, but the median wt-CYP3A5 mRNA was 4-fold higher in CYP3A5*1/*3 livers compared with CYP3A5*3/*3 livers. Differences in wt-CYP3A5 and CYP3A4 mRNA content explained 53 and 51% of the interliver variability in CYP3A5 and CYP3A4 content, respectively. Hepatic CYP3A4 and CYP3A5 contents were not correlated when all livers were compared. However, for CYP3A5*1/*3 livers, levels of the two proteins were strongly correlated (r = 0.93) as were wt-CYP3A5 and CYP3A4 mRNA (r = 0.76). These findings suggest that CYP3A4 and CYP3A5 genes share a common regulatory pathway for constitutive expression, possibly involving conserved elements in the 5'-flanking region.

Alleles↗

PubMed2002

Study of efferent tube suspension as a continent diversion mechanism. an experimental study in dogs.

PURPOSE: To construct a reliable continent tube, which is easy to catheterize and surgically simple. MATERIALS AND METHODS: 8 adult female mongrel dogs underwent a procedure in which an ileal segment was tapered as an efferent tube. The tapered ileum was fixed to the back surface of the rectus muscle with a polyester taper 1.5 cm in width and a suspension tension of 400 g. The internal orifice of the tapered ileum was anastomosed to the bladder and the external orifice of the tapered ileum was brought out to the abdominal skin. Urodynamic and radiological studies were carried out postoperatively in all dogs. RESULTS: All stomas in dogs could be easily catheterized with a 14-french catheter. Urodynamic study of the efferent tubes showed that the maximum closure pressure ranged from 117 to 157 (mean 136.75) cm water. Retrograde radiogram of the efferent tubes showed perfect canalization without stenosis. CONCLUSION: This study suggests that the continent mechanism of the tapered ileum can be greatly enhanced by a suspension technique.

Animals↗

PubMed2002

An experimental study of colonic mucosal graft for urethral reconstruction.

OBJECTIVE: To investigate the possibility of urethral reconstruction with a free colonic mucosal graft. METHODS: Ten female dogs underwent a procedure in which the urethral mucosa was totally removed and replaced with a free graft of colic mucosa. A urodynamic study was performed before the operation and sacrifice. The dogs were sacrificed 8 to 16 weeks after the operation for histological examination of the urethra. RESULTS: Urethral stricture developed in 1 dog. The results of urody namic studies showed that the difference in maximum urethral pressure between pre-operation and pre-sacrifice in the remaining 9 dogs was not of significance (P > 0.05). Histological examination revealed that the colonic free mucosa survived inside the urethral lumen of the 9 dogs. Plicae surface and unilaminar cylindric epithelium of the colonic mucosa was observed in dogs sacrificed 8 weeks after the operation. Plicae surface and unilaminar cylindric epithelium of the colonic mucosa was not observed and metaplastic transitional epithelium covered a large proportion of the urethral mucosa in dogs sacrificed 12 weeks after the operation. CONCLUSIONS: Urethral mucosa can be replaced by colonic mucosa without damaging the continence mechanism in female dogs. This technique is useful when local or preputial skin and buccal or bladder mucosa are not available.

Animals↗

PubMed2002

[Interventional therapy for the chronic seminal vesiculitis].

OBJECTIVES: To investigate the efficacy of transperineal seminal vesicle puncture under ultrasound guidance and continuous transcatheter antibiotic drugs instillation for the treatment of chronic seminal vesiculitis. METHODS: Forty-two patients with hemospermia were treated from April 1988 to January 2001. Of them 35 patients with urogenital inflammation were treated by transperineal seminal vesicle puncture under ultrasound guidance and continuous transcatheter antibiotic drugs instillation. RESULTS: Transperineal seminal vesicle puncture and continuous transcatheter antibiotic drugs instillation therapy was adopted for 35 patients with urogenital inflammation and the cure rate was 91.43%. CONCLUSIONS: Transperineal seminal vesicle puncture under ultrasound guidance and continuous transcatheter antibiotic drugs instillation was an effective method for diagnosis and treatment of chronic seminal vesiculitis.

Adult↗

PubMed2002

Urodynamic study of enhanced continent mechanism using tapered ileum as continent urinary reservoir.

OBJECTIVE: To investigate the effect of extramural support from the pouch and abdominal wall to enhance the continent mechanism of tapered ileum. METHODS: A total of 24 patients underwent a procedure in which an ileal segment was tapered into an efferent tube, of which a part was placed between the back surface of the rectus muscle and the ileal pouch wall. The internal orifice of the tapered ileum was anastomosed to the ileal pouch and its external orifice was anastomosed to the umbilicus. A urodynamic study of the efferent tubes and pouch was done 1.5 to 3 months and 6 to 24 months postoperatively. RESULTS: One patient died of heart disease 55 days postoperatively, while 22 of the remaining 23 were completely continent day and night. At 1.5 to 3 months, the urodynamic study of the efferent tubes demonstrated that the maximum closure pressure with a full pouch was 46 - 124 cmH(2)O (91.26 +/- 15.71 cmH(2)O) and with an empty pouch was 34 - 84 cmH(2)O (67 +/- 10.60 cmH(2)O). The difference in mean maximum closure pressure in the full and empty pouches was statistically significant (t = -11.78 and P = 0.00001). At 6 to 24 months, a second urodynamic study was performed on 18 cases, demonstrating a reservoir capacity of 420 to 750 ml (481.67 +/- 78.83 ml). Reservoir pressure was 6 to 9 cmH(2)O (7.17 +/- 1.17 cmH(2)O) when the pouch was filled to 50 ml, and 16 to 35 cmH(2)O (24.12 +/- 5.61 cmH(2)O) when it was filled to maximum capacity. There was no contractive wave during the filling in any patient. Maximum closure pressure in the efferent tube was 80 to 194 cm H(2)O (98.89 +/- 26.34 cmH(2)O) when the pouch was filled with saline, and 64 to 128 cmH(2)O (74.78 +/- 14.54 cmH(2)O) when the pouch was empty. The difference in mean maximum closure pressure in the full and empty pouches was statistically significant (t = -7.58 and P = 0.00003). CONCLUSIONS: This study indicates that the continent mechanism of tapered ileum may be greatly enhanced by extramural support from the abdominal and pouch walls.

Adult↗