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Biomedical subjects

A D Joyce

Publications and source records attributed to A D Joyce.

28 records · Page 2Linked to original sources

Elevated expression of pp60c-src in low grade human bladder carcinoma.

The results presented in this report demonstrate that the tyrosine-specific protein kinase activity of pp60c-src is elevated over that recorded in normal bladder mucosa in a subset of human bladder carcinomas. Increased kinase activity was observed mainly in low grade bladder lesions and was associated, at least in part, with elevated levels of pp60c-src expression. Extension of this analysis to a panel of human bladder carcinoma cell lines confirmed previous observations of low pp60c-src kinase activity in three lines established from high grade (GIII) bladder tumors and revealed increased kinase activity in three alternative bladder lines derived from GI or GII tumors. Use of an anti-phosphotyrosine antibody in Western blot analysis revealed the presence of novel phosphotyrosyl cellular substrates in human bladder cell lines and tumors displaying elevated pp60c-src kinase activity. These observations suggest an association for the src protooncogene in urothelial cell differentiation events.

Blotting, Western↗

Extracorporeal shock wave lithotripsy of ureteric stones with the Modulith SL 20.

A series of 138 patients with ureteric calculi was treated by in situ extracorporeal shock wave lithotripsy (ESWL) during the clinical introduction of the Modulith SL 20. This machine represents a newly developed lithotriptor with an electromagnetic cylinder as shock wave source and a dual localisation system consisting of in-line ultrasound and an integrated fluoroscope C-arm. During the first 2 months, 12 patients (phase 1) were treated under ultrasound localisation alone; during the next 5 months, 37 patients (phase 2) were treated using dual imaging modalities with reduced peak pressure (max. 18 kV = 800 bar); during the final 7 months, 89 patients (phase 3) were treated under ultrasonic and fluoroscopic localisation combined with an increased maximal shock wave pressure (20 kV = 1024 bar). The introduction of fluoroscopic targeting (phases 2 and 3) resulted in satisfactory localisation of calculi in the mid-ureter, previously limited by use of only coaxial ultrasound. The extension of stone localisation to the whole length of the ureter was associated with a marked decrease in treatment time, reflecting the easy handling of the dual localisation system. The rise in generator voltage (phase 3) improved the disintegration rate from 81% (phase 2) to 85%, whereas the number of impulses remained unchanged. However, the rate of auxiliary procedures following ESWL (adjuvant and curative) was reduced from 33% (phase 2) to 24.5%. Thus the Modulith SL 20 in its final design enables in situ ESWL to be the treatment of choice for all ureteric calculi, rendering special positioning techniques or multiple treatment unnecessary.

Humans↗

ras induced lesions in a heterotopic mouse bladder.

To determine the in vivo phenotype elicited in bladder epithelium following the expression of a ras oncogene we have introduced the HaSV ras transforming gene into transplants of normal urothelium. Stripped adult bladder mucosa incubated with HaSV, in the presence or absence of helper virus, was transplanted beneath the renal capsule of syngeneic animals and maintained for periods up to three months. Control implants, exposed to helper virus alone, formed heterotopic bladders lined by urothelium displaying focal areas of full differentiation when associated with underlying submucosal elements. Exposure of urothelium to HaSV resulted in increased proliferative potential of mucosal and submucosal elements with the appearance of a normal differentiated heterotopic bladder 10 days post-implantation. Implants left for 28 days presented a range of hyperplastic lesions (mild-severe) characterized from histological evaluation and antibody markers recognizing basal (D66) and superficial cell populations (H10) in normal bladder mucosa. Staining of mild hyperplastic lesions revealed an increased basal cell compartment and a loss of fully differentiated cells lining the lumen of the implanted bladder. In severe hyperplasia no superficial cells were observed but mucosal elements stained throughout with antibody D66. This phenotype was accompanied by an irregular laminin staining pattern associated with a disorganized basement membrane and increased blood vasculature. Similar experiments conducted with HaSV and helper virus resulted in the generation of mesenchymal lesions at 28 days with little surviving urothelium. The H-ras oncogenic protein can induce hyperplastic lesions in normal urothelium which were characteristic of preneoplastic changes identified in bladder carcinogenesis.

Animals↗

Hepatobiliary tumours of childhood: investigation and management.

The most commonly encountered complications include wound infections, subphrenic collections and bile leaks from the cut liver surface. Stress ulceration of the stomach or duodenum is also not uncommon. Inadvertent bile duct damage has also been reported after major resection in children. The results of surgery for benign lesions are very good and usually depend simply on technical expertise. The results for malignant lesions, however, remain poor. Six series, including our own experience, reported in the last 5 years have shown an overall survival rate of 43% for patients whose tumours were resected for cure. It is difficult to compare results as authors differ in their presentation of results, but details of the series are listed in Table 7. There were no definite prognostic factors to be drawn from these series other than that children with the fibrolamellar variant of hepatocellular carcinoma fared better than those with other hepatomas. It is a sad fact that overall 56% of patients in these series presented with unresectable disease. Mahour et al. described seven patients with unresectable disease who were treated by either chemotherapy alone or in combination with radiotherapy, followed by 'second look' laparotomy and resection. Five of these patients were alive and disease-free for a minimum of 2.5 years after surgery. Thus it is necessary to adopt an aggressive approach to these tumours if one is to see any improvement on the overall figures.

Bile Duct Neoplasms↗

Microvascular anastomoses in diabetes: an experimental study.

The process of intimal repair across a microvascular anastomosis has been studied in an animal model of diabetes using scanning electron microscopy. The mean area of re-endothelialisation at 10 days, 200 microns on either side of an experimental microarterial anastomosis, was 65% in nondiabetic controls compared to 16.5% in an untreated diabetic group and 10% in an insulin treated diabetic group. The degree of intimal repair was significantly lower in the diabetic groups compared to controls (p less than 0.01, Wilcoxon Rank Test). Defective re-endothelialisation may contribute to anastomotic failure in clinical practice.

Anastomosis, Surgical↗

Detection of altered H-ras proteins in human tumors using western blot analysis.

H-ras p21 protein expression was investigated in bladder and colonic tumor tissues using an H-ras specific antibody in Western blot analysis. The specificity of this antibody to H-ras proteins was established using NIH/3T3 transfectants expressing oncogenic counterparts of the different ras gene family members. Use of this antibody to detect altered H-ras proteins was demonstrated using a panel of transfectants bearing different mutated H-ras genes and established cell lines previously characterized in transfection assays. Extension of this technique to direct analysis of human tumor material confirmed previous observations of H-ras activation within a group of bladder tumors and identified three more urothelial tumors expressing altered H-ras proteins. The altered migrational properties of these three were suggestive of point mutational events in 12 (1 case) and 61 (2 cases) codon hot spots. This study extends previous observations on the preferential activation of H-ras in urinary tract tumors and provides a rapid technique for evaluating the status of H-ras proteins in human tumor tissue.

Antibody Specificity↗

The subrenal capsule: an alternative site for the maintenance of normal and preneoplastic urothelium.

Implantation of normal bladder mucosa beneath the kidney capsule of a syngeneic animal, results in a heterotopic bladder lined by a one to three cell layer of urothelium. This cystic structure can be maintained for greater than 90 days and displays many of the differentiation characteristics of a normal bladder, both at the light and electron microscopy level. Preneoplastic urothelial cells behave in a similar manner recreating a heterotopic bladder lined by urothelium displaying aberrant differentiation and surface morphology. All tumorigenic cell lines tested in this model produced solid tumor growth within a few weeks. The subrenal capsule represents an alternative site for the reconstitution of urothelial material at different stages of neoplastic progression.

Animals↗

Transplantation of immortalized bladder epithelial cell lines in denuded mouse bladder.

The temporal and spatial regeneration of denuded mouse bladders was characterized using antibody markers to mucosal and submucosal elements in bladder tissue. Mechanical stripping of bladder mucosa resulted in a plane of cleavage in the submucosa leaving the muscle layers intact. Fully regenerated bladders were observed after 14 to 21 days although submucosal elements showed abnormal vacuolation. Implantation of immortalized epithelial cell line BBN3 into denuded bladders resulted in solid tumor formation while, in contrast, transplantation of MB331 showed cystic structures with no indication of invasion. Confirmation of the epithelial and implanted origin of cells lining the lumina of implanted bladders were shown using different keratin antibodies. The benign behavior of MB331 in vivo is suggestive of a cell line representing a preneoplastic stage in carcinogenesis and demonstrates an approach to assess the in vivo phenotype of cell parameters established in vitro.

Animals↗

Abdominal incisions--vertical or transverse?

Two-hundred and nine patients were entered into a prospective, randomized trial in order to determine whether a vertical or transverse abdominal incision is the more satisfactory in producing sound wounds. Ninety-six patients were randomized between paramedian and transverse incisions, and followed up for at least 1 year. No significant difference in the incidence of wound failure could be shown between 46 paramedian and 50 transverse incisions. Those patients who were considered to require a vertical incision were randomized between median and paramedian incisions. No significant difference in wound failure rates between 39 median and 40 paramedian incisions could be demonstrated. No advantage or disadvantage of a transverse over a vertical abdominal incision or of a paramedian over a median incision could be shown in this study.

Abdomen↗