Biomedical subjects

J J Yoo

Publications and source records attributed to J J Yoo.

21 records · Page 2Linked to original sources

PubMed1997

Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder.

The epidermal growth factor receptor (HER1) has been implicated in regenerative growth and proliferative diseases of the human bladder epithelium (urothelium), however a cognate HER1 ligand that can act as a growth factor for normal human urothelial cells (HUC) has not been identified. Here we show that heparin-binding EGF-like growth factor (HB-EGF), an activating HER1 ligand, is an autocrine regulator of HUC growth. This conclusion is based on demonstration of HB-EGF synthesis and secretion by primary culture HUC, identification of HER1 as an activatable HB-EGF receptor on HUC surfaces, stimulation of HUC clonal growth by HB-EGF, inhibition of HB-EGF-stimulated growth by heparin and of log-phase growth by CRM 197, a specific inhibitor of HB-EGF/HER1 interaction, and identification of human urothelium as a site of HB-EGF precursor (proHB-EGF) synthesis in vivo. ProHB-EGF expression was also detected in the vascular and detrusor smooth muscle of the human bladder. These data suggest a physiologic role for HB-EGF in the regulation of urothelial proliferation and regeneration subsequent to mucosal injury. Expression of proHB-EGF is also a feature of differentiated vascular and detrusor smooth muscle in the bladder. Because proHB-EGF is known to be the high affinity diphtheria toxin (DT) receptor in human cells, synthesis of the HB-EGF precursor by human urothelium also suggests the possibility of using the DT-binding sites of proHB-EGF as an in vivo target for the intraluminal treatment of urothelial diseases.

Bacterial Proteins↗

PubMed1997

Detachable self-sealing membrane system for the endoscopic treatment of incontinence.

PURPOSE: The endoscopic treatment of urinary incontinence is limited by the injectable substances currently available. The ideal injectable material should be able to conserve its volume, be nonmigratory and nonantigenic. Toward this goal we developed a system for the treatment of incontinence in which a catheter with an inflatable and detachable self-sealing silicone membrane fits through a standard cystoscopic needle. We present our experience with this system. MATERIALS AND METHODS: A total of 20 female beagle dogs underwent cystoscopy and in 15 a self-sealing membrane was placed endoscopically in the submucosal region of the proximal urethra at the 3 and 9 o'clock positions. Each membrane was inflated through the delivery catheter with 0.2 cc povidone. Coaptation of the urethra due to the relative bulking effect of the inflated membrane was confirmed endoscopically in each animal. Five control animals received only an injection of saline. Four animals were sacrificed at 1, 3, 6, 12 and 18 months, respectively. At sacrifice gross and histological examinations were performed. RESULTS: At retrieval up to 18 months after implantation the membrane remained inflated and at the same position at which it had been initially placed. There was no evidence of povidone volume loss or extravasation. Membranes were encapsulated by a fibrous capsule. Only a few inflammatory cells surrounded the capsule by month 1 and there were none by month 3. Histological examination of periurethral tissue and distant organs showed no evidence of particle migration. CONCLUSIONS: The detachable self-sealing membrane system is easily implantable, nonmigratory, nonantigenic and able to conserve its volume. These studies indicate that this system may be effective for the endoscopic treatment of incontinence.

Animals↗

PubMed1997

A novel gene delivery system using urothelial tissue engineered neo-organs.

PURPOSE: Presently gene delivery is most effectively achieved by ex vivo gene transfer, which includes removal of the target tissue, in vitro gene delivery to the target cells, possible selection to enhance the proportion of transfected cells and reintroduction of the gene modified cells. Reintroduction of transformed cells in vivo has been a challenging task. Based on the feasibility of tissue engineering techniques in which cells seeded on biodegradable polymer scaffolds form tissue when implanted in vivo, we explored the possibility of developing a neo-organ system for in vivo gene therapy. MATERIALS AND METHODS: Normal human urothelial cells were harvested, expanded in vitro and seeded on biodegradable polymer scaffolds. The cell-polymer complex was then transfected with PGL3-luc, pCMV-luc and pCMV beta-gal promoter reporter gene constructs. The transfected cell-polymer scaffolds were then implanted in athymic mice and the engineered tissue was retrieved 0, 1, 3, 5 and 7 days after implantation. RESULTS: The reporter gene assay demonstrated an expression of luciferase activity at days 1, 3, 5 and 7 with the peak at day 5. X-gal and beta-galactosidase antibody assays stained positive on the deoxyribonucleic acid treated transfection. CONCLUSIONS: Successful gene transfer can be achieved using biodegradable polymer scaffolds as a urothelial cell delivery vehicle. The transfected cell-polymer scaffold forms an organ-like structure with functional expression of the transfected genes. This study demonstrates that urothelial tissue engineered gene transfer is safe and effective.

Animals↗