A processive versus a distributive mechanism of action correlates with differences in ability of normal and xeroderma pigmentosum group A endonucleases to incise damaged nucleosomal DNA

A DNA endonuclease, isolated from the nuclei of normal human and xeroderma pigmentosum complementation group A (XPA) cells, which recognizes predominately pyrimidine dimers, was examined for the mechanism by which it locates sites of damage on UVC-irradiated DNA. In reaction mixtures with low ionic strengths (i.e. lacking KCl), the normal and XPA endonuclease locate sites of UV damage on both naked and reconstituted nucleosomal DNA by different mechanisms. On both of these substrates, the normal endonuclease acts by a processive mechanism, meaning that it binds non-specifically to DNA and scans the DNA for sites of damage, whereas the XPA endonuclease acts by a distributive one, meaning that it randomly locates sites of damage on DNA. However, while both the normal and XPA endonucleases can incise UVC irradiated naked DNA, they differ in ability to incise damaged nucleosomal DNA. The normal endonuclease showed increased activity on UVC treated nucleosomal DNA compared with naked DNA, whereas the XPA endonuclease showed decreased activity on the damaged nucleosomal substrate. Since a processive mechanism of action is sensitive to the ionic strength of the micro-environment, the KCl concentration of the reaction was increased. At 70 mM KCI, the normal endonuclease switched to a distributive mechanism of action and its ability to incise damaged nucleosomal DNA also decreased. These studies show that there is a correlation between the ability of these endonucleases to act by a processive mechanism and their ability to incise damaged nucleosomal DNA; the normal endonuclease, which acts processively, can incise damaged nucleosomal DNA, whereas the XPA endonuclease, which acts distributively, is defective in ability to incise this substrate.      

A new amino acid mixture permits new approaches to the treatment of phenylketonuria

A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance.     

Exploratory Study of Women's Reactions to Having a Cesarean Birth

ABSTRACT: One hundred and five women who had cesarean sections were interviewed to assess their feelings about their births. Forty-one percent of the women were told they had to have a cesarean fewer than two hours before, and 35% were repeat cesareans. Statistical data are presented on women's reasons for feeling cesareans were harder, easier, or not different, including the finding that 30% felt relief at having a cesarean. Sources of stress and negative feelings after cesareans are discussed.     

Novel everting urologic access sheath: decreased axial forces during insertion

BACKGROUND: Advancement of urologic instruments through the genitourinary tract is associated with significant axial forces that likely contribute to patient discomfort, even after injection of a local anesthetic, and may lead to mucosal trauma, postprocedural dysuria and hematuria, and increased susceptibility to infection and strictures. Placing an everting urethral sheath prior to instrumentation may decrease these problems. Materials and METHODS: Two 7-cm-long, 5-mm diameter urethral luminal models were created, one with and one without an artificial stricture. We measured the forces generated during advancement of a novel everting access sheath (Cystoglide; Percutaneous Systems, Mountain View, CA) through the models in comparison with a representative cystoscope and a urologic dilator simulating a traditional access sheath. RESULTS: The mean force generated during advancement of the everting sheath was significantly less than that of both the representative cystoscope (P<0.01) and the traditional access sheath (P<0.01). This held true for the urethral models both with and without an artificial stricture (P<0.01) and with and without lubrication (P<0.01). CONCLUSIONS: This novel introduction sheath markedly decreased the axial forces applied to an artificial urethral luminal wall. It is possible that the clinical use of this technology will decrease the discomfort and potential complications associated with lower urinary-tract endoscopy.     

Clinical and urodynamic evaluation after ureterocystoplasty and kidney transplantation

PURPOSE: We assessed clinical and surgical results in renal transplantation candidates with voiding dysfunction and end stage renal disease who underwent bladder augmentation. MATERIALS AND METHODS: We analyzed 8 patients 3 to 30 years old with dilated ureters, voiding dysfunction and end stage renal disease who underwent renal transplantation following bladder augmentation from 1995 to 2003. The etiology of bladder dysfunction was neurogenic bladder in 3 patients, posterior urethral valves in 3 and vesicoureteral reflux in 2. All cases were assessed by ultrasonography, voiding cystourethrography and urodynamic studies. RESULTS: Mean followup was 50 months (range 4 to 93). Previous urodynamic evaluation revealed a bladder capacity of 75 to 294 ml (mean +/- SD 167.38 +/- 77.32) and an intravesical pressure of 28 to 100 mm H2O (mean 51.25 +/- 22.17). Urodynamic study after augmentation and kidney transplantation showed a bladder capacity of 191 to 400 ml (mean 335.25 +/- 99.01) and an intravesical pressure of 15 to 35 mm H2O (mean 28 +/- 9.45). Mean serum creatinine was 1.65 mg/dl (range 0.8 to 2.5). All patients remained continent. Three patients with neurogenic bladder empty the bladder by clean intermittent catheterization and the others empty by the Valsalva maneuver. None of the grafts were lost and the most common complication was asymptomatic urinary tract infection. CONCLUSIONS: Bladder augmentation is a well-known procedure for low capacity and poorly compliant bladders even in candidates for a renal transplant. Ureterocystoplasty combines the benefits common to all enterocystoplasties without adding to complications or risks.