Cellular pathophysiology of cystic kidney disease: insight into future therapies.

Polycystic kidney disease (PKD) is a developmental kidney disorder which can be inherited as either an autosomal dominant trait, with an incidence of 1:50 to 1:1000, or as an autosomal recessive trait with an incidence of 1:6,000 to 1:40,000. Three different genes have now been cloned that are associated with mutations that cause PKD. Two of these are linked to the most common forms of the dominant disease while the third is associated with the orpk mouse model of recessive polycystic kidney disease. Advances in understanding the molecular genetics of PKD have been paralleled by new insights into the cellular pathophysiology of cyst formation and progressive enlargement. Current data suggest that a number of PKD proteins may interact in a complex, which when disrupted by mutations in PKD genes may lead to altered epithelial proliferative activity, secretion, and cell matrix biology. The identification of a unique cystic epithelial phenotype presents new opportunities for targeted therapies. These include targeted gene therapy, gene complementation, and specific immunological or pharmacological interruption of growth factor pathways.     

Experimental investigation of the scaphoid strain during wrist motion

The scaphoid is the most frequently fractured of the carpal bones [Taleisnik, J., The Wrist, Churchill Livingstone, New York (1985)]. This project was undertaken to qualitatively evaluate the strain in the scaphoid during wrist motion using a newly developed strain gage method. Strain gage resettes were mounted within the scaphoid and the range of motion of the hand was monitored using a custom designed electrogoniometer and data acquisition system. Ten specimens were utilized for this study. Results indicated that supination/pronation (S/P) of the forearm did not affect the strain in the scaphoid. A map of the strain in the waist of the scaphoid, as a function of flexion/extension (F/E) and radial/ulnar deviation (R/U), was generated. The contour plot of scaphoid strain vs range of motion (ROM) shows a valley where strains are low. Minimum scaphoid strain was found near neutral F/E and 15° of ulnar deviation.     

Partial characterization of the secretory material from the dorsal bodies in the snail Helisoma duryi (Mollusca: Pulmonata), and its effects on reproduction

Abstract. Both dorsal body tissue extracts and dorsal body-conditioned medium stimulated in vitro polysaccharide synthesis in albumen gland explants in Helisoma duryi . This activity is heat- and protease-resistant. Dorsal body tissue extracts and dorsal body-conditioned medium were passed through solid-phase extraction cartridges, then eluted with increasing concentrations of methanol (20%, 70%, and 100%) and the various eluates tested for their biological activity. An active factor was found in the 100% methanol wash from both dorsal body tissue extracts and the conditioned medium. In addition, another bioactive factor in the conditioned medium eluted with 70% methanol. The endocrine dorsal bodies in the freshwater snail H. duryi were maintained in vitro , and following incubation, the culture medium was collected and tested for the presence of ecdysteroids. Radioimmunoassay of the culture medium demonstrated the presence of ecdysteroid-like immunoreactivity, suggesting the dorsal bodies are capable of secreting ecdysteroids in vitro . Identification of released ecdysteroids by HPLC/RIA revealed a number of immunoreactive fractions, which were tested for bioactivity. To test for possible physiological functions of ecdysteroids in Helisoma duryi , 20-hydroxyecdysone (a potent ecdysteroid in arthropods) was injected into non-egg laying (virgin) snails. Injections of ecdysteroid induced low egg-laying activity and the maturation of oocytes in the ovotestis. Incubation of albumen glands with ecdysteroid stimulated polysaccharide synthesis. The results are discussed in relation to the possible function(s) of ecdysteroids in pulmonate snails.     

Expression of new KDN-gangliosides in rainbow trout testis during spermatogenesis and their structural identification

The developmental expression of 2-keto-3-deoxy-D-glycero-D-galacto-nononicacid-containing glycosphingolipids (KDN-gangliosides) in rainbowtrout testis during spermatogenesis was studied using a monoclonalantibody, mAb.kdn3G, which recognizes the KDN     

The diversity of ectomycorrhizal fungi associated with introduced Pinus spp. in the Southern Hemisphere, with particular reference to Western Australia

Accepted: 15 June 1998     

Evidence for dietary essentiality of lithium in the rat

The purpose of this study was to determine the dietary essentiality of lithium (Li) in rats. In three experiments, two types of diets were fed during growth, reproduction, and lactation. In the first experiment, dams were maintained on a corn-based diet containing 2 ng or 500 ng (controls) Li/g through five successive periods of pregnancy and lactation. The offspring of dams fed the low-Li diet had significantly lower weaning weights (p=0.011), and the percent weaned was lower (p=0.094) than that of controls. In the second experiment, rats were maintained through three generations on a rice-based diet containing 0.6 ng Li/g, or the control (500 ng/g) diet. There was a significant effect of Li level on litter size (p=0.017) and litter wt at birth (p=0.006) in the third generation. The overall effect through three generations on litter wt at birth approaches statistical significance (p=0.086). In the third experiment, third-generation rats were continued on the respective rice-based diets with three levels of dietary sodium, the normal level, one-half, and four times that level. The litter size and birth wt were significantly lower (p=0.0030 and 0.0038, respectively) among the low-Li dams that consumed the normal and high-sodium levels compared to those that consumed the low-sodium diets. The interaction of Li and sodium as regards litter wt at birth approached significance (p=0.083). Various tissues of the rats in the third experiment were analyzed for Li. It seems likely that Li exerts an essential nutrient role for the rat. Contribution of the Missouri Agricultural Experiment Station, Journal Series No. 11,327.     

Assignment of anomeric configurations of pyranose sugars in oligosaccharides using a sensitive FAB-MS strategy

This paper describes a sensitive strategy employing fast atom bombardment mass spectrometry (FAB-MS) for defining the anomeric configurations of pyranose sugars in oligosaccharides. The method, which is applicable to mixtures of reduced or unreduced oligosaccharides, is based upon FAB-MS analyses of deuteroacetylated derivatives before and after oxidation with chromium trioxide. This reagent, whose potential value in carbohydrate chemistry was first recognized by Angyal and which was subsequently more fully exploited by Lindberg, oxidizes beta-pyranosides to keto-esters leaving alpha-pyranosides largely intact. In this paper we show that the products of chromium trioxide oxidation can be successfully analysed at the microgram level using FAB-MS. The molecular and fragment ions produced in the FAB experiment define the number of sites oxidized and their location in the sequence. For samples which fragment poorly we describe a mild methanolysis procedure, compatible with FAB-MS, which preferentially cleaves the esters formed during the oxidation. Incorporation of an acetolysis step prior to oxidation permits analyses of polysaccharides. This oxidation/FAB-MS strategy should prove valuable in structural analyses of a wide range of biologically important carbohydrates which cannot be isolated in sufficient quantities to permit nuclear magnetic resonance studies.