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Biomedical subjects

Jiong Zhang

Publications and source records attributed to Jiong Zhang.

At least 19 recordsLinked to original sources

[Clinical analysis of operative treatment of 191 patients with posterior urethral strictures].

OBJECTIVE: To evaluate the various operative details of strictures of the posterior urethra that are essential for a successful result. METHODS: The clinical data of 191 patients with posterior urethral strictures or distraction defects from January 1990 to January 2006 were analyzed retrospectively. All patients underwent a retrograde and voiding urethrogram, 62 patients had urethral ultrasonography, 48 patients had urethroscopy, 3 patients had MRI. Repair was performed with a simple anastomosis after urethral mobilization in 66 patients, separation of the corporeal bodies in 48 patients, separation of the corporeal bodies and inferior pubectomy in 30 patients, transpubic anastomosis in 18 patients, pull-through operation in 3 patients, and optical urethrotomy in 26 patients. Followup ranged from 6 to 48 months. RESULTS: The mean stricture length was 3.6 cm (range from 1.5 to 8.0 cm). Posterior urethral strictures is in 31 (16%), posterior distraction defects is in 160 (84%), of which the length of the distraction defects < 3 cm is in 102 (53.4%), and the the length of the distraction defects > 3 cm is in 58 (30.6%). The overall successful results (Qmax > 15 ml/s) after operation was 84.3%. Optical urethrotomy was 69%, the successful results with anastomotic urethroplasty were 97% with a simple anastomosis; 79% with separation of the corporeal bodies; 80% with separation of the corporeal bodies and inferior pubectomy; 83% with transpubic anastomosis; and 67% with pull-through operation. CONCLUSIONS: The anastomotic urethroplasty is better than the optical urethrotomy, the length of the strictures or distraction defect which is lower than 3 cm is much more successfully corrected.

Adolescent↗

Sequence-specific detection of femtomolar DNA via a chronocoulometric DNA sensor (CDS): effects of nanoparticle-mediated amplification and nanoscale control of DNA assembly at electrodes.

We herein report a novel nanoparticle-based electrochemical DNA detection approach. This DNA sensor is based on a "sandwich" detection strategy, which involves capture probe DNA immobilized on gold electrodes and reporter probe DNA labeled with gold nanoparticles that flank the target DNA sequence. Electrochemical signals are generated by chronocoulometric interrogation of [Ru(NH(3))(6)](3+) that quantitatively binds to surface-confined capture probe DNA via electrostatic interactions. We demonstrated that the incorporation of a gold nanoparticle in this sensor design significantly enhanced the sensitivity and the selectivity. Nanoscale control of the self-assembly process of DNA probes at gold electrodes further increased the sensor performance. As a result of these two combined effects, this DNA sensor could detect as low as femtomolar (zeptomoles) DNA targets and exhibited excellent selectivity against even a single-base mismatch. In addition, this novel DNA sensor showed fairly good reproducibility, stability, and reusability.

DNA↗

Screening for inter-individual splicing differences in human GSTM4 and the discovery of a single nucleotide substitution related to the tandem skipping of two exons.

The glutathione S-transferase Mu class (GSTM) genes encode phase II metabolism enzymes that are involved in the detoxification of various carcinogens and drugs. Some genetic polymorphisms in GSTM genes are related to disease phenotypes and drug-metabolism differences in the population. Polymorphisms that alter gene-splicing patterns are functionally very important because they often lead to the insertion or deletion of many amino acids. To identify inter-individual differences in the splicing pattern of the GSTM4 gene, we used reverse transcriptase polymerase chain reaction (RT-PCR) to screen cDNA from 96 human liver samples. We discovered a novel splice variant of GSTM4 that resulted from tandem skipping of exons 4 and 5. This exon-skipping event is associated with a mutation at the splice acceptor site in intron 4.

DNA, Complementary↗

[The treatment of complex urethral stricture greater than 8 cm long].

OBJECTIVE: To evaluate the selection of different procedures and the feasibility for the treatment of long segment urethral stricture. METHODS: Seventy-six patients with complex urethral stricture greater than 8 cm long underwent different procedures of urethroplasty. Of them various mucosa grafts urethral reconstruction were adopted in 42 cases (colonic mucosal graft, n = 26; buccal mucosal graft, n = 10; bladder mucosal graft, n = 6); One-stage pedicle flaps urethroplasty in 20; two-stage urethroplasty of Johanson procedure in 12; and penile urethra-prostatic urethra anastomosis, three-stage urethroplasty in 2. RESULTS: In early followed up (within 6 months postoperatively), 67 patients (88%) voided well and complications developed in 10. Among the 70 patients who lasted more than 1 year after operation, 51 cases were followed up. Forty-four patients voided well, and complications developed in 8. Of the 8 cases urethral restructure developed in 2 (18%) for pedicle flaps urethroplasty, 2 for colonic mucosal urethroplasty (9%), 1 for buccal mucosal graft (1/7), 1 for bladder mucosal graft (1/3); penile chordee in 2 (2/5), and one of them was accompanied by hair bearing neourethra for two-stage urethroplasty of Johanson procedure. CONCLUSIONS: Colonic mucosal and buccal mucosal grafts urethroplasty are feasible procedures for the treatment of long segment urethral stricture, and Colonic mucosal graft urethroplasty may be considered when more conventional procedures fail or complicated urethral strictures greater than 10 cm long.

Adolescent↗

An evaluation of surgical approaches for posterior urethral distraction defects in boys.

PURPOSE: We present our preliminary experience with operative approaches in the treatment of complex posterior urethral distraction defects in children. MATERIALS AND METHODS: A total of 24 boys 7 to 14 years old with obliterative complex posterior urethral distraction defects were treated with 1 of 3 surgical approaches between January 1998 and December 2002. A perineal approach was used in 5 cases, a transperineal-inferior pubic approach including distal urethral mobilization, corporeal body separation and inferior pubectomy in 10, and a combined transpubic-perineal approach in 9. RESULTS: Patients were followed 1 to 5 years postoperatively. A successful result of no recurrence of stricture was achieved in 19 of 24 patients (79.2%), including 3 of 5 (60%) treated with a perineal approach, 9 of 10 (90%) with a transperineal-inferior pubic approach and 7 of 9 (77.8%) with a transpubic-perineal approach. Complications included 1 combined false passage, which was resolved using a transperineal-inferior pubic approach, 2 urethrocutaneous fistulas, which were resolved using a perineal approach in 1 and a transpubic-perineal approach in 1, and 3 rectourethral fistulas, which were resolved using a transpubic-perineal approach in 1 and a transperineal-inferior pubic approach in 1. Of the 9 patients treated with the transpubic-perineal approach 3 walked with an abnormal gait postoperatively. CONCLUSIONS: The transperineal-inferior pubic approach fully exposes the space behind the pubis, does not damage pelvic stability and yields better results compared to the perineal and transpubic-perineal approaches. We recommend it as first line operative treatment for complex posterior urethral distraction defects in boys.

Adolescent↗

Modeling oligonucleotide microarray signals.

Chemical principles dictate that the specific binding of a target to its complementary probes on a DNA microarray surface, and the nonspecific binding between other nucleotide segments and the same probes, are mutually competitive. We demonstrate that this mechanism can be understood by considering the competitive chemical reaction taking place on the microarray surface. Inspired by the pioneering work of Zhang and Hekstra, we have developed a physical model for microarray signal analysis, based on possible reaction mechanisms, and implemented it with a parallel, generic, simulated-annealing algorithm. Using data supplied by the Affymetrix Latin-square spike-in experiments, our model showed excellent fitting of the data. This correlation between the predicted expression levels and the spike-in concentrations of test transcripts demonstrated good predictive abilities of our model.

Algorithms↗

Inter-individual variation of several cytochrome P450 2D6 splice variants in human liver.

To examine the possibility that inter-individual differences in splicing partially explain the observed differences in CYP2D6 activity, we amplified its full-length cDNA in 96 human liver RNA samples and discovered five splice variants: intron 5 retention, intron 6 retention, intron 5 and intron 6 double retention, exon 3 skipping, and partial intron 1 retention. All of the CYP2D6 splice variants we identified are probably nonfunctional transcripts. Substantial inter-individual variation in the proportions of the CYP2D6 transcript represented by splice variants, measured by real-time PCR, suggests that the presence of these splice variants contributes to the population variation in CYP2D6 activity. Relatively high levels of intron 6 retention were not correlated with the newly discovered single nucleotide polymorphism 2988G > A in intron 6 (CYP2D6*41) but did correlate with the more common CYP2D6*34 allele. Our study prompts further investigations to explore the effect of these splice variants on drug metabolism.

Base Sequence↗

[Ultrasonographic assessment of urethral condyloma acuminatum in men].

OBJECTIVE: To evaluate the value of ultrasonography in diagnosing urethral condyloma acuminatum (CA) in men. METHODS: Twenty-two male patients, aged 36 +/- 19, diagnosed as with urethral CA based on history and clinical symptoms underwent ultrasonography and urethroscopy. The patients were asked to micturate to distend the urethra. The posterior urethra was detected by transrectum approach. Transperineal scans were performed to image the bulbar urethra, scrotal urethra and penile urethra. The sonographically positive results were compared with the pathological results. RESULTS: Eighty-three vegetations were found in the anterior urethra of seventeen patients, and eighty-one vegetations were diagnosed as CA by pathology, of which 1.2% were polyp shape, 38.3% papillary shape, and 60.5% cauliflower mass. Sonourethrography was an accurate predictor of papillary shape and cauliflower mass; however, it was difficult to differentiate between polyp shape vegetation and crystal. CONCLUSION: Sonourethrography is a sensitive and accurate tool not only for primary diagnosis of but also for follow-up of urethral CA in men.

Adolescent↗

Distribution of exonic splicing enhancer elements in human genes.

Ab initio prediction of functional exon splicing enhancer (ESE) elements based on RNA sequences present a challenge in the evaluation of the functional impacts of human genetic polymorphisms on splicing. To better understand the behavior of ESEs, we studied their distribution in human exons and introns for four known SR protein-binding motifs: SF2/SAF, SC35, SRp40, and SRp55. ESEs are enriched in regions in exons that are close to the splice sites, especially in the region 80 to 120 bases away from the ends of splice acceptor sites. Significant enrichment of ESEs is associated with weak splice acceptor sites but not weak donor sites. ESE density decreases at the 3 ends of long exons. ESEs are also enriched in introns with weak donor or acceptor sites. These characteristics of ESEs may help to predict functional ESE sites in RNA sequences.

Alternative Splicing↗

Sequential analysis of tacrolimus dosing in adult lung transplant patients with ABCB1 haplotypes.

The genetic polymorphisms in the ABCB1 gene, which encodes for the membrane pump, P-glycoprotein, have been previously demonstrated to have an association with tacrolimus dosing in organ transplant patients. This study associated the haplotype and genotype for ABCB1 G2677T and C3435T variants with a sequential analysis of tacrolimus blood level (ng/mL) per mg/day dosage ([L/D]) administered to 91 adult lung transplant patients at 1, 3, 6, 9, and 12 months after transplantation. Haplotype 22 carriers had a significantly higher tacrolimus [L/D] value in comparison with nonhaplotype 22 carriers (P = .04) only at 1 month after transplant. Sequential analysis demonstrated that ABCB1 genotypes 00 and 01 had low tacrolimus [L/D] values at 1 and 3 months, but these values increased substantially at 6, 9, and 12 months after transplantation. This was not true of the other genotypes with the exception of genotypes 10 and 21, which had small numbers of patients but had consistently low tacrolimus [L/D]. Haplotype analysis also suggested that the homozygous for ABCB1 2677 variant allele had more of an impact on tacrolimus [L/D] in haplotype analysis than that of ABCB1 3435. In conclusion, sequential analysis of tacrolimus [L/D] with haplotypes can explain previous clinical observations of changes in tacrolimus dosage over time but suggests that this effect is limited to individual patient haplotypes. Sequential analysis of drug dosing and haplotypes relationships can provide important information about the induction or inhibition of drug-drug and disease-drug interactions among specific haplotypes.

ATP-Binding Cassette Transporters↗

1-stage urethral reconstruction using colonic mucosa graft for the treatment of a long complex urethral stricture.

PURPOSE: We investigated the possibility of urethroplasty with a free graft of colonic mucosa for long, complex urethral strictures. We report our initial experience with colonic mucosa graft urethroplasty for such urethral strictures in 16 patients. MATERIALS AND METHODS: Between September 2000 and December 2002, 16 patients with a long, complex urethral stricture were treated with colonic mucosal graft urethroplasty. Patients had undergone an average of 2.5 previous unsuccessful repairs. Urethral reconstruction was done with a 10 to 17 cm (median 13) graft of colonic mucosa RESULTS: Patients were followed 6 to 33 months postoperatively. Meatal stenosis that developed in 1 patient 3 months postoperatively needed reoperation. The patient was voiding well with a urinary peak flow of 28.7 ml per second during 9-month followup after reoperation. Hyperplasia of the verumontanum was observed during urethroscopy and transurethral colliculectomy was performed in 1 patient more than 14 months postoperatively. Uroflowmetry showed a urinary peak flow of 46.5 ml per second postoperatively. The other patients were voiding well with a urinary peak flow of greater than 15 ml per second. Urethrogram revealed a patent urethra with an adequate lumen and no significant graft sacculation. CONCLUSIONS: This initial experience in 16 patients indicates that colonic mucosa graft urethroplasty is a feasible procedure for long, complex anterior urethral strictures. The technique may be considered for urethral reconstruction when more conventional procedures have failed.

Adolescent↗

Tacrolimus dosing in adult lung transplant patients is related to cytochrome P4503A5 gene polymorphism.

Tacrolimus is a potent immunosuppressive agent used in lung transplantation and is a substrate for both P-glycoprotein (P-gp, encoded by the gene MDR1) and cytochrome (CYP) P4503A. A previous study by the authors identified a correlation between the tacrolimus blood level per dose with CYP3A5 and MDR1 gene polymorphisms in pediatric heart transplant patients. The objective of this study was to confirm the influence of these polymorphisms on tacrolimus dosing in adult lung transplant patients. Adult lung transplant patients who had been followed for at least 1 year after lung transplantation were studied. Tacrolimus blood level (ng/mL) per dose (mg/day) at 1, 3, 6, 9, and 12 months after transplantation was calculated as [L/D]. DNA was extracted from blood. MDR1 3435 CC, CT, and TT; MDR1 2677 GG, GT, and TT; and CYP3A5*1 (expressor) and *3 (nonexpressor) genotypes were determined by PCR amplification, direct sequencing, and sequence evaluation. Eighty-three patients were studied. At 1, 3, 6, 9, and 12 months after the transplant, a significant difference in [L/D] was found between the CYP3A5 expressor versus nonexpressor genotypes (mean +/- SD of 1.49 +/- 0.88 vs. 3.11 +/- 4.27, p = 0.01; 1.23 +/- 0.82 vs. 3.44 +/- 8.97, p = 0.05; 1.32 +/- 0.96 vs. 3.81 +/- 6.66, p = 0.005; 0.95 +/- 1.19 vs. 3.74 +/- 5.98, p = 0.0015; and 0.45 +/- 0.2 vs. 3.76 +/- 6.75, p = 0.0001, respectively). MDR1 G2677T and C3435T genotypes had only minimal effects on [L/D] at 1 and 3 months after transplantation. This study confirms the relationship of CYP3A5 polymorphisms to tacrolimus dosing in organ transplant patients. CYP3A5 expressor genotypes required a larger tacrolimus dose to achieve the same blood levels than the CYP3A5 nonexpressors at all time points during the first posttransplant year. This was not uniformly true for MDR1. The authors therefore conclude that tacrolimus dosing in adult lung transplant patients is associated with CYP3A5 gene polymorphisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[One-stage urethroplasty using colonic mucosa in the treatment of complex lengthy urethral stricture].

OBJECTIVE: To investigate the feasibility of urethral reconstruction with colonic mucosa graft in the treatment of complex lengthy urethral stricture. METHODS: Between October 2000 and May 2003, 19 male patients with complex lengthy urethral stricture that had undergone unsuccessful urethral repair 3 times on average, aged 18 - 65, were treated with free graft of colonic mucosa 10 to 17 cm (mean 13.2 cm) long. The patients were followed-up for 6 - 36 months (17 months on average) by retrograde urethrography, urethroscopy, and uroflometry. RESULTS: Meatal stenosis that needed reoperation was developed in 1 patient 3 months postoperatively. This patient became voiding very well with a urinary peak flow of 28.7 ml per second during the follow-up of 12 months after the second operation. Hyperplasia of verumontanum was observed during urethroscopy in 1 patient 14 months postoperatively. Uroflometry examination showed a urinary peak flow of 46.5 ml/s after transurethral colliculectomy. The other 17 patients were voiding well with a urinary peak flow greater than 15 ml/s (16 to 28.5 ml/s). CONCLUSION: Colonic mucosa graft urethroplasty is a feasible procedure for the treatment of complex lengthy urethral stricture, particularly when the more conventional options fail or are contraindicated.

Adolescent↗

Tacrolimus dosing in pediatric heart transplant patients is related to CYP3A5 and MDR1 gene polymorphisms.

Tacrolimus is a substrate for P-glycoprotein (P-gp) and cytochrome (CYP) P4503A. P-gp is encoded by the multiple drug resistance gene MDR1 and CYP3A is the major enzyme responsible for tacrolimus metabolism. Both MDR1 and CYP3A5 genes have multiple single nucleotide polymorphisms. The objective of this study was to evaluate whether the MDR1 exon21 and exon26 polymorphisms and the CYP3A5 polymorphism are associated with tacrolimus disposition in pediatric heart transplant patients. At 3, 6 and 12 months post transplantation, a significant difference in tacrolimus blood level per dose/kg/day was found between the CYP3A5 *1/*3 (CYP3A5 expressor) vs. *3/*3 (nonexpressor) genotypes with the *1/*3 patients requiring a larger tacrolimus dose to maintain the same blood concentration. There were no significant differences in tacrolimus blood level per dose/kg/day between MDR1 exon21 G2677T and exon 26 C3435T at 3 months, but both were found to have a significant association with tacrolimus blood level per dose/kg/day at 6 and 12 months. We conclude that specific genotypes of MDR1 and CYP3A5 in pediatric heart transplant patients require larger tacrolimus doses to maintain their tacrolimus blood concentration, and that this information could be used prospectively to manage patient's immunosuppressive therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

One-stage urethral reconstruction using colonic mucosa graft: an experimental and clinical study.

AIM: To investigate the possibility of urethral reconstruction with a free colonic mucosa graft and to present our preliminary experience with urethral substitution using a free graft of colonic mucosa for treatment of 7 patients with complex urethral stricture of a long segment. METHODS: Ten female dogs underwent a procedure in which the urethral mucosa was totally removed and replaced with a free graft of colonic 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 urethra. Besides, 7 patients with complex urethral stricture of a long segment were treated by urethroplasty with the use of a colonic mucosal graft. The cases had undergone an average of 3 previous unsuccessful repairs. Urethral reconstruction with a free graft of colonic mucosa ranged from 10 to 17 cm (mean 13.1 cm). Follow-up included urethrography, urethroscopy and uroflowmetry. RESULTS: Urethral stricture developed in 1 dog. The results of urodynamic studies showed that the difference in the maximum urethral pressure between the 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 10 experimental dogs. Plicae surface and unilaminar cylindric epithelium of the colonic mucosa was observed in dogs sacrificed 8 weeks after the operation. The 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. Clinically, the patients were followed up for 3-18 months postoperatively (mean 8.5 months). Meatal stenosis was developed in 1 patient 3 months postoperatively and needed reoperation. The patient was voiding very well with urinary peak flow 28.7 ml/s during the follow-up of 9 months after reoperation. The other patients were voiding well with urinary peak flow greater than 15 ml/s. Urethrogram revealed a patent urethra with an adequate lumen with no significant graft sacculation. Neither necrosis of neourethral mucosa nor stenosis at the anastomosis sites has been observed on urethroscopy in 4 patients over 6 months after operation. CONCLUSION: Urethral mucosa can be replaced by colonic mucosa without damaging the continence mechanism in female dogs. Colonic mucosa graft urethral substitution is a feasible procedure for the treatment of complex urethral stricture of a long segment. The technique may be considered when more conventional options have failed or are contraindicated.

Adult↗

Efferent tube suspension as a continent diversion mechanism: a preliminary report of a clinical study.

PURPOSE: We constructed a reliable continent tube that is surgically simple. MATERIALS AND METHODS: In 12 patients with malignant bladder tumor we performed radical cystectomy with isolation of a 50 cm. ileal loop with pedicle. The proximal segment (8 to 10 cm.) was tapered over a 16Fr catheter as an efferent tube, the remaining segment was detubularized to create a W-shape pouch and the tapered ileum was fixed to the back surface of the rectus muscle with 2 polyester tapers 1 cm. wide with a suspension tension of 500 g. The external orifice of the tapered ileum was anastomosed to the umbilicus. In 2 patients with neuropathic bladder a 15 cm. ileal loop with pedicle was isolated, the proximal segment (8 cm.) was tapered as an efferent tube with 500 g. suspension tension, and the remaining segment was detubularized and anastomosed to the bladder. RESULTS: The patients were followed for 6 to 17 months (mean 11.4) and were completely continent day and night. The stoma was easily catheterized with a 16Fr catheter in all cases. Urodynamic study of the efferent tubes revealed maximum pressure of 84 to 159 cm. water (mean 114). Retrograde radiography of the efferent tubes demonstrated perfect canalization without stenosis. CONCLUSIONS: This study suggests that the continent mechanism of the tapered ileum can be greatly enhanced by a suspension technique. This maneuver also provides easy catheterization and surgical simplicity.

Adolescent↗

The MDR1 polymorphisms at exons 21 and 26 predict steroid weaning in pediatric heart transplant patients.

Various polymorphisms of the MDR1 gene that encodes for P-glycoprotein (P-gp), a transmembrane pump, have been identified. A silent mutation C3435T in exon 26 and a G2677T mutation in exon 21 have been correlated with P-gp expression and function in humans. The objectives of this study were (a) to determine whether the MDR1 exon 21 and exon 26 polymorphisms were related to steroid weaning in a pediatric heart transplant (HTx) population, and (b) to determine whether an association exist between the MDR1 exon 21 and exon 26 polymorphisms in these patients. Sixty-nine pediatric HTx patients were studied. MDR1 genotyping was determined by polymerase chain reaction amplification, sequencing the DNA, and sequence evaluation using Polyphred software (University of Washington) to identify genotypes. The steroid dose at 1 year post-transplantation was recorded. For steroid weaning at one year post-HTx for MDR1 C3435T, 12 of 18 (67%) patients in the CC genotype were still on prednisone, whereas only 18 of 47 (38%) of the CT/TT group were still receiving prednisone (p = 0.04). Similar results were observed for the MDR1 G2677T genotyping and steroid weaning. Forty-three of 46 patients (93.5%) who have MDR1 C3435T allele also have a mutant G2677T allele (p < 0.001). We conclude that (a) a significantly larger number of MDR1 3435 CC HTx patients remain on steroids at 1 year after transplantation, and (b) the MDR1 C3435T genotype is associated with the G2677 genotype in pediatric HTx patients.

Adolescent↗