Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Cell surface associated glycohydrolases in normal and Gaucher disease fibroblasts

Gaucher disease (GD) is the most common lysosomal disorder and is caused by an inherited autosomal recessive deficiency in \u3b2-glucocerebrosidase. This enzyme, like other glycohydrolases involved in glycosphingolipid (GSL) metabolism, is present in both plasma membrane (PM) and intracellular fractions. We analyzed the activities of CBE-sensitive \u3b2-glucosidase (GBA1) and AMP-DNM-sensitive \u3b2-glucosidase (GBA2) in total cell lysates and PM of human fibroblast cell lines from control (normal) subjects and from patients with GD clinical types 1, 2, and 3. GBA1 activities in both total lysate and PM of GD fibroblasts were low, and their relative percentages were similar to those of control cells. In contrast, GBA2 activities were higher in GD cells than in control cells, and the degree of increase differed among the three GD types. The increase of GBA2 enzyme activity was correlated with increased expression of GBA2 protein as evaluated by QRT-PCR. Activities of \u3b2-galactosidase and \u3b2-hexosaminidase in PM were significantly higher for GD cells than for control cells and also showed significant differences among the three GD types, suggesting the occurrence of cross-talk among the enzymes involved in GSL metabolism. Our findings indicate that the profiles of glycohydrolase activities in PM may provide a valuable tool to refine the classification of GD into distinct clinical types

Adjuvant single-dose upper urinary tract instillation of mitomycin C after therapeutic ureteroscopy for upper tract urothelial carcinoma: a single-centre prospective non-randomized trial

Purpose To address the safety and feasibility of upper urinary tract instillation of a single dose of mitomycin (ASDM) immediately after therapeutic ureteroscopy for upper tract urothelial carcinoma (UTUC) and to compare urothelial (ipsilateral or bladder) recurrence rates in the ASDM group and controls. Materials and Methods Between April 2015 and August 2018, 52 patients affected by UTUC were treated by endoscopic ablation, of whom 26 were selected for ASDM. Clinical and perioperative data and 30-day complications were recorded. The primary endpoint was urothelial recurrence-free survival (URFS) evaluated by second-look ureteroscopy and CT scan/ureteroscopy every 6 months. Results ASDM was administered via a single-J (19/25, 76%) or a double-J (6/25, 24%) in 25/26 (96%) patients. Median follow-up was 18 months (IQR 10-29). The urothelial recurrence rate was 23.5% and 55.5% in the ASDM group and controls, respectively (p=0.086). Mean URFS was 28.8 months in the ASDM group vs 18.8 months in controls (log-rank p=0.067). On multivariate Cox regression, ASDM was associated with a 7.7-fold lower risk of urothelial recurrence (HR=0.13; 95% CI 0.03-0.65; p=0.01). Clavien grade 64II complications occurred in 32% (8/25) and 30.7% (8/26) of the ASDM and control group, respectively (p=0.9). Two Clavien III complications occurred in the ASDM group: bladder haematuria after concomitant TURB and obstructive kidney failure in a single-kidney patient. Conclusions ASDM was well tolerated after therapeutic ureteroscopy. It appears to reduce the risk of urothelial recurrence in patients affected by low-grade UTUC without bladder tumour. Therefore, its use should be evaluated