A mutant form of the Wilms' tumor suppressor gene WT1 observed in Denys-Drash syndrome interferes with glomerular capillary development

The Wilms' tumor suppressor gene WT1 encodes a zinc finger protein that is required for urogenital development. In the kidney, WT1 is most highly expressed in glomerular epithelial cells or podocytes, which are an essential component of the filtering system. Human subjects heterozygous for point mutations in the WT1 gene develop renal failure because of the formation of scar tissue within glomeruli. The relationship between WT1 expression in podocytes during development and glomerular scarring is not well understood. In this study, transgenic mice that expressed a mutant form of WT1 in podocytes were derived. The capillaries within transgenic glomeruli were dilated, indicating that WT1 might regulate the expression of growth factors that affect capillary development. Platelet endothelial cell adhesion molecule-1 expression was greatly reduced on glomerular endothelial cells of transgenic kidneys. These results suggest that WT1 controls the expression of growth factors that regulate glomerular capillary development and that abnormal capillary development might lead to glomerular disease.     

A prospective evaluation of patients undergoing surgery for the palliation of an advanced malignancy

Background Decisions regarding the use of surgical procedures for the palliation of symptoms caused by advanced malignancies require the highest level of surgical judgment. Prospective analysis of palliative surgical care may facilitate a more effective and representative evaluation of these patients. Methods Patients requiring surgery planned solely for the palliation of an advanced malignancy were offered entry onto this study. Outcome measurements were made before surgery and monthly thereafter until the patient’s death. Accepted techniques of pain assessment, quality of life, and functional status were used. Results Between May 1997 and December 1999, 26 patients were enrolled. Although 46% (12 of 26) of patients demonstrated improvement in pain control or quality of life after palliative surgery, these benefits lasted a median of only 3.4 months. Palliative surgery was associated with significant postoperative complications in 35% (9 of 26) patients. Conclusions Although many patients had no apparent demonstrable benefit from surgery, surgeons were able to identify a group of patients who experienced significant benefits after a palliative procedure. The relationships between the patient and family members and the surgeon play an important role in decision-making throughout the palliative phase of cancer treatment. The opirions and assertions herein are the private ones of the authors and are not to be construed as official policy or reflecting the views of the Department of Defense.     

The nature of a denture base: a key factor in denture sore mouth

Sections of both the polished and the impression basal surfaces of polymethyl methacrylate, vulcanite, and cast-gold denture base materials were examined and photographed using scanning electron microscopy. An attempt was made to draw attention to some of the key factors related to the tissue tolerance to these materials.     

Molecular specificity of 5-androstenediol as a systemic radioprotectant in mice

We compared in vivo radioprotective efficacy of 5-androstenediol (5-AED) to that of ten other steroids: 17alpha-androstenediol, dehydroepiandrosterone, 5-androstenetriol (AET), 4-androstenedione (AND), testosterone, estradiol, fluasterone, 16alpha-bromoepiandrosterone, 16alpha-fluoro-androst-5-en-17alpha-ol (alpha-fluorohydrin, AFH), and 16alpha-fluoro-androst-5-en-17beta-ol (beta-fluorohydrin). Steroids were administered 24 or 48 hr before, or 1 hr after, whole-body gamma-irradiation. Two days after irradiation at 3 Gy, blood elements were counted. In addition, after irradiation at 9-12.5 Gy, survival was recorded for 30 days. The results showed radioprotective efficacy was specific for 5-AED. One other steroid, AFH, demonstrated appreciable survival effects but was less efficacious than 5-AED. AND and AET produced slight enhancement of survival in some experiments. This is the first demonstration that the prophylactic window for survival enhancement by 1 subcutaneous (s.c.) injection of 5-AED is as long as 48 hr in mice. Moreover, the results indicate that 1 s.c. injection of 5-AED 1 hr after irradiation is much less effective than 1 injection 24-48 hr before irradiation. Comparing the molecular features of steroids with radioprotective efficacy leads to the following conclusions: 1) these effects are due to interaction with specific receptors, since s.c. injection of extremely similar molecules with the same physicochemical properties as 5-AED were not radioprotective; 2) the 17-hydroxyl group is essential; 3) this group must be in the beta configuration in the absence of nearby side groups; 4) a halogen atom at 16 changes the 17-hydroxyl specificity to alpha; 5) the 3beta-hydroxyl group is not essential; 6) addition of a 7beta-hydroxyl group is deleterious; and 7) the effects are not due to activation of sex steroid receptors.