Looking upon the water. Surprises.
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Biomedical subjects
Publications and source records attributed to K D Gardner.
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The influence of environment on renal cyst growth was assessed in experiments utilizing 56 germ-free and 32 conventional male Sprague-Dawley rats fed 2% nordihydroguaiaretic acid (NDGA). Among three groups of six germ-free rats allowed ad lib intake of NDGA for six weeks and deconditioned (placed into the ambient laboratory environment) at the start, at the midpoint, or not at all, cyst formation and interstitial changes (both severe) were noted only among animals deconditioned at the midpoint. Among 14 germ-free rats that were offered 0.4 g NDGA daily, deconditioned after two weeks, and sacrificed 0 to 15 days thereafter, nephron dilation and thymidine uptake by renal tubular epithelium appeared within one to three days and correlated in magnitude with each other and with the duration of the contamination interval. Deconditioning, a prior period of four or more days of exposure to NDGA in the germ-free state, the duration of the contamination period, and the presence of cecal flora were identified as prerequisites to accelerated cyst formation in this model, while the dose of ingested NDGA, the presence of bacteria within the kidney, an action of bacteria on NDGA within the colon, and the type(s) of organisms colonizing the host were not. These findings provide experimental evidence that environmental circumstance can modulate the expression of renal cystic disease.
We have used scanning electron microscopy (SEM) to examine the surface morphology of the renal epithelial cell lines MDCK and LLC-PKl to determine the influence of alternative culture substrate conditions on cell polarity. We observed that regardless of physical culture conditions, cells established and maintained polarity, expressed by the characteristics of apical and basal surfaces. Culture conditions did, however, influence the orientation of cell polarity in vitro. MDCK cells were grown within collagen gel, in which individual cells exhibited clonal growth to form fluid-filled epithelial cysts. The cells of MDCK-cysts were polarized with apical surface facing the lumen and basal surface against the surrounding collagen gel. This configuration made it possible to gain direct visual access, by SEM, to the basal surface by removing the supportive collagen lattice. The apical surface of MDCK-cysts was lined by short microvilli. Each cell possessed a solitary cilium. In comparison, the basal surface had few appendages, although cell boundaries were marked by interdigitating short processes. LLC-PKl cells in monolayer culture bore solitary cilia and long microvilli at their apical surface. The basal surface of cells involved in dome formation was observed to possess only a sparse population of short, blunt processes. When LLC-PKl cells were raised in stationary suspension culture or in monolayer atop non-culture grade plastic, they formed cysts with the cell apex facing the surrounding medium. These cells showed variable apical morphology. The cells of large, highly expanded cysts were often attenuated and had a relatively smooth apical surface. The basal surface of cells of fractured LLC-PKl cysts commonly was also smooth, without prominent appendages.
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Substantial contributions to the field of RCD have been made over the past 15 years. Most intriguing is a growing awareness of acquired RCD and its complications. Data have been published and are reviewed here in support of a possibility that APKD and RCD acquired during hemodialysis are premalignant lesions. More data are needed before the possibility can be confirmed or denied. The collection of these data is an immediate need in the field of RCD.
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Intranephron hydrostatic pressures were monitored while microperfusing proximal nephrons in diphenylthiazole (DPT)-exposed kidneys, a model in which increased compliance of tubular basement membrane is thought to predispose to cyst formation. Structural studies subsequently were done on these and additional kidneys. Results were compared to those obtained from the study of kidneys from normal rats. Intranephron hydrostatic pressures were shown to rise with microperfusion and did so at lower rates of perfusion among DPT exposed nephrons. For example, at four perfusion rates between 17 and 36 nl/min (60 to 130% of the SNGFR in DPT-fed rats), intranephron hydrostatic pressures were 6 to 14 cm H2O higher (P less than 0.05) in DPT-exposed kidneys. Subsequent light and electron microscopic examination of DPT-exposed kidneys showed micropolyps partially occluding inner medullary and intrapapillary collecting ducts. DPT-induced renal cystic disease resembles other forms of chemically induced renal cystic disease in its functional and structural parameters save that micropolyp formation appears to occur nearer the papillary tip. We conclude that conditions in the DPT-exposed rat kidney resemble more closely those predicted by the partial obstruction rather than by the increased compliance hypothesis of renal cyst formation.
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The pathophysiology of anuric hyperglycemia is characterized by changes in extracellular fluid volume and in effective osmolality. We studied these changes in 7 anuric patients during correction (seven instances) or development (one instance) of hyperglycemia. During observations, intakes and outputs of fluids were negligible and weights did not change. Pulmonary edema, present in hyperglycemia in six instances, disappeared with normalization of glucose concentration in five instances. While glucose was rising, before study, thirst and water intake were pronounced in six instances; in three, normalization of glucose concentration uncovered true hyponatremia. For the same change in blood glucose, changes in effective osmolality were greatest in patients with anasarca.
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In experimental models of cystic renal disease, functional studies define conditions that suggest increased resistance to outflow from dilated or cystic nephrons. Morphologically, models exhibit foci of cellular hyperplasia and micropolyp formation along outer medullary collecting tubules. Temporally, cellular proliferation precedes cyst formation. These findings in models have led to a hypothesis that polypoid hyperplasia participates in cyst formation in susceptible kidneys by increasing resistance to the outflow of tubular urine. The present study was undertaken to establish the presence, extent, and distribution of cellular hyperplasia in human adult polycystic kidney disease. Kidneys from four unrelated individuals were studied by light and by transmission and scanning electron microscopy. Foci of hocation of hyperplasia along the nephron were similar to those seen in the models. These findings delineate a heretofore unappreciated morphologic similarity between the models and human disease and add further support to the hypothesis that partial rubular obstruction participates in the pathogenesis of renal cystic disease, whether it be heritable or acquired, in animals and in man.