Gretchen S. Mandel

ASYMMETRIC ACYLATION REACTIONS OF CHIRAL IMIDE ENOLATES. THE FIRST DIRECT APPROACH TO THE CONSTRUCTION OF CHIRAL β-DICARBONYL SYNTHONS

Acylation de 2 propionimides chirales: isopropyl-4 propionyl-3 oxazolidone-2 et methyl-4 phenyl-5 propionyl-3 oxazolidone-2

Urinary Tract Stone Disease in the United States Veteran Population. II. Geographical Analysis of Variations in Composition

The geographical distribution of crystalline components observed in urinary tract stones in the continental United States has been studied in the United States veteran population. Since the veteran population is at risk for urolithiasis the National Veterans Administration Crystal Identification Center was established in 1983 for the characterization of all crystal-containing veteran patient samples using high resolution x-ray powder diffraction. The geographical distribution of whewellite, weddelite, apatite, brushite, struvite, uric acid and uric acid dihydrate is presented. The percentage occurrence of the crystalline components, percentage occurrence of admixed stones and geographical distribution of the number of components in admixed stones also are presented. The data highlight that although the southeastern United States has the highest patient discharge rate for stones, this high discharge rate appears to be correlated specifically with a high discharge rate for calcium oxalate stones and not with a high discharge rate for any of the other common stone components.

Study of a rat model for calcium oxalate crystal formation without severe renal damage in selected conditions

Abstract  Background:  Although nephrotoxic in high doses, ethylene glycol (EG) has been used with ammonium chloride (NH4Cl) or vitamin D3 to study calcium oxalate stone formation in rat models. In the present study we used EG alone or with NH4Cl to study hyperoxaluria, crystaluria, and crystal attachment to renal epithelial cells in rats with minimal renal damage.

Membrane Interactions with Calcium Oxalate Crystals: Variation in Hemolytic Potentials with Crystal Morphology

Crystal-induced membranolysis of human red blood cells has been quantitated for calcium oxalate monohydrate and calcium oxalate dihydrate crystals. Calcium oxalate monohydrate crystals are significantly more membranolytic than calcium oxalate dihydrate crystals at constant surface area. If the crystal morphology of calcium oxalate monohydrate is altered by grinding, the lytic potential at constant surface area is markedly reduced. However, altered calcium oxalate dihydrate crystals are as lytic as natural calcium oxalate dihydrate crystals at constant surface area. Differences in the calcium oxalate monohydrate and dihydrate crystal structures, specifically the structural characteristics of the disordered water channel in calcium oxalate dihydrate, can explain these different membranolytic characteristics.

Urinary tract stone disease in the United States veteran population. I. Geographical frequency of occurrence.

The geographical distribution of hospitalization for urinary tract stone disease in the continental United States has been studied in the United States veteran population. The current study has been facilitated by the availability of a centralized computer data base containing the International Classification of Disease Codes for all hospital discharges at all Veterans Administration medical facilities. These data have allowed for an accurate mapping of the hospital discharge rate for urinary tract stone disease (stone discharge rate) in a population at risk for urolithiasis. Stone discharge rate data have been compared to those from the 2 previous studies conducted in general hospitals in 1952 and 1974. The stone discharge rate was 7.9 +/- 3.4 in 1952, 9.97 +/- 2.82 in 1974 and 7.58 +/- 2.01 in our study. These data indicate that the urinary tract stone discharge rate has not markedly varied during the last 34 years and also that the southeastern states still evidence the highest hospital discharge rate for urinary tract stone disease.

Regulation of pH in rat papillary tubule cells in primary culture.

To investigate the mechanisms responsible for urinary acidification in the terminal nephron, primary cultures of cells isolated from the renal papilla were grown as monolayers in a defined medium. Morphologically, cultured cells were epithelial in type, and similar to collecting duct principal cells. Cell pH measured fluorometrically in monolayers grown on glass slides showed recovery from acid loads in Na+-free media. Recovery was inhibited by cyanide, oligomycin A, and N-ethylmaleimide. Cyanide and oligomycin inhibited recovery less in the presence than in the absence of glucose. When cells were first acid loaded in a Na+-free medium and then exposed to external Na+, pH recovery also took place. This recovery exhibited first-order dependence on Na+ concentration and was inhibited by 5-(N-ethyl-N-isopropyl)amiloride. These studies demonstrate that in culture, collecting duct principal cells possess at least two mechanisms for acid extrusion: a proton ATP-ase and an Na+-H+ exchanger. The former may be responsible for some component of the urinary acidification observed in the papillary collecting duct in vivo; the role of the latter in acid-base transport remains uncertain.

Calcium Oxalate Crystal Interaction with Rat Renal Inner Papillary Collecting Tubule Cells

Rat renal inner papillary collecting tubule cells (RPCT) have been isolated and maintained in primary culture. The cells have been found to be of only one type and they have maintained the characteristics of RPCT cells. The RPCT cells in culture appear as a monolayer with intermittent clumps of rounded cells. When small calcium oxalate monohydrate crystals (COM) or calcium oxalate dihydrate crystals (COD) are added to the monolayer of RPCT cells, the crystals bind on or about these clumps of rounded-up cells. The use of this system as a model for the study of crystal membrane interactions in crystalluria and urolithiasis is discussed.

Effect of Particle Size on Quartz-Induced Hemolysis and on Lung Inflammation and Fibrosis

To assess the role of crystal size in biologic responses, we quantitated red blood cell lysis and lung inflammation and fibrosis in the mouse using 4 alpha-quartz preparations with average diameters of 1, 5, 7.8, and 11.2 microns. When compared on the basis of identical crystal surface areas, the 1-micron fraction was more hemolytic than the other 3 fractions. The three larger fractions had equivalent membranolytic activities. After 6 weeks of postintratracheal instillation of the crystals into mice, the 1-micron-diameter crystal fraction increased wet lung weights by 1.25 x that of saline controls, while a 1.75 x increase was found for the three larger crystal fractions. A similar response was found when evaluating fibrosis development by determining lung hydroxyproline levels. Measurement of the percentage of the crystal dose remaining in the lungs revealed that the biologic differences observed were not due to a difference in the clearance of the smaller crystal fraction. Thus, larger crystals of alpha-quartz produce a greater degree of inflammation and fibrosis when instilled into the lung than those of 1 micron diameter, even though the smaller crystals are more membranolytic in vitro and appear to be cleared from the lung at the same rate as the larger crystals.

The role of complement in experimental silicosis

The role of the complement system in the pathogenesis of crystal-induced pulmonary inflammation and fibrosis was evaluated using a mouse model of silicosis and congenitally complement-deficient mice. Mice lacking the fifth component of complement (B10.D2/o) were compared to C5-sufficient animals (B10.D2/n) for pulmonary changes following intratracheal instillation of silica crystals. Complement-deficient mice demonstrated a significant reduction compared to complement-sufficient mice in both cell number and protein content of lung lavage fluid throughout the 12 weeks following silica exposure. Lung hydroxyproline content (indicative of collagen deposition) was equivalent for both strains and significantly higher than controls at all time points following silica instillation. Moreover, studies in vitro have shown that silica crystals are capable of activating complement via the alternative pathway. These studies indicate that the complement system may be responsible for some of the pulmonary inflammation, but not fibrosis elicited by silica exposure.

The effect of hydroxyapatite crystallinity on hemolysis.

SummaryCrystalline hydroxyapatite is a component of bone, teeth, and numerous pathological calcifications. The apatite crystal structure can accommodate a wide variety of atomic substitutions which gives apatite crystals an unusually high degree of variability in biochemical and physical properties. Apatite crystallites interact with numerous cellular systemsin vivo, and some of these interactions may lead to altered cellular function. One measure of crystal-membrane interactions is crystal-induced membranolysis of human red blood cells. Hemolytic potentials at constant crystal surface areas were measured at 1, 2, and 4 hours for 29 different preparations of apatite. Each apatite sample was characterized by its morphology, particle size, % CO3, zeta potential, and broadening of the (211), (112), (300), (202), and (002) diffraction maxima. Only the surface area/g and the X-ray powder diffraction line broadening showed a significant inverse correlation with hemolytic potential. These parameters were related to each other, and are indications of the degree of crystallinity.