Biomedical subjects

J R Neuringer

Publications and source records attributed to J R Neuringer.

8 recordsLinked to original sources

PubMed1994

Strategies to slow the progression of renal disease.

Recent multicenter clinical trials have confirmed that it is indeed possible to slow the progression of chronic renal disease in patients with diabetic and nondiabetic nephropathy. Antihypertensive therapy is particularly protective in this regard, either due to the lowering of blood pressure or, as is sometimes the case with ACE inhibition, to mechanisms independent of a systemic hemodynamic effect. Similarly, strict glycemic control has now clearly been shown to ameliorate the progression of diabetic nephropathy, while dietary protein restriction appears to have some benefit, although further studies will be required to establish this definitively. Finally, preliminary data suggest that some of these therapies may also slow progression in patients with renal transplant nephropathy, which has unfortunately become an increasingly common cause of ESRD. These encouraging results will hopefully stimulate further efforts to elucidate the mechanisms by which progression occurs, so that even better therapies can be designed.

Antihypertensive Agents↗

PubMed1993

Hemodynamic theory of progressive renal disease: a 10-year update in brief review.

Experimental studies have suggested that glomerular hypertension is ultimately damaging to the kidney. Prevention of glomerular hypertension by dietary protein restriction or antihypertensive therapy lessens glomerular injury in several experimental models of chronic renal disease. Glomerular hypertension and hyperfiltration also occur in humans with diabetes mellitus, solitary or remnant kidneys, and various forms of acquired renal disease. Clinical studies are beginning to show that dietary protein restriction and antihypertensive therapy may slow progression in these disorders. Large multicenter trials are currently under way to better define the effects of these therapeutic maneuvers on the progression of chronic renal disease.

Animals↗

PubMed1992

Glomerular hypertension: cause and consequence of renal injury.

BACKGROUND: Glomerular capillary hyperfiltration and hypertension occur in certain disease states and also in response to a reduction in the number of functional nephrons. Experimental studies have shown that these glomerular hemodynamic changes are maladaptive, and ultimately damaging to the kidney. Amelioration of glomerular hyperfunction by dietary protein restriction or antihypertensive therapy lessens glomerular injury in several experimental models of chronic renal disease. THESIS: Hyperfiltration may similarly occur in humans with diabetes mellitus, a solitary or remnant kidney, or acquired renal disease. There is evidence to suggest that these people may therefore be at increased risk for the development of renal injury. CURRENT RESEARCH: Clinical studies have shown that dietary protein restriction and antihypertensive therapy may beneficially affect the course of chronic renal failure in humans. Large multicenter trials are currently underway on the effects of these therapeutic maneuvers on the progression of chronic renal disease.

Antihypertensive Agents↗

PubMed1991

Nitric oxide: a potential mediator of amino acid-induced renal hyperemia and hyperfiltration.

The role of nitric oxide in the modulation of systemic and renal hemodynamics was examined by using N omega-monomethyl-L-arginine (L-NMMA, 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused intravenously into anesthetized euvolemic Munich-Wistar rats. After 30 min, L-NMMA resulted in a uniform increase in mean arterial blood pressure (111 +/- 1 to 128 +/- 2 mmHg; P less than 0.05) and a modest reduction in renal plasma flow rate (4.4 +/- 0.2 to 4.2 +/- 0.1 mL/min; P less than 0.05), without change in glomerular filtration rate (1.16 +/- 0.03 to 1.15 +/- 0.03 mL/min); vehicle had no effect on these renal parameters. These rats were then subdivided to receive an intravenous infusion (37 microL/min) of either 10% glycine, 11.4% mixed amino acids, or equiosmolar dextrose. L-NMMA pretreatment markedly attenuated glycine-induced hyperfiltration (10 +/- 6 versus 33 +/- 5%, L-NMMA versus vehicle; P less than 0.05) and obliterated the renal hyperemic response (-7 +/- 6 versus 16 +/- 4%, L-NMMA versus vehicle; P less than 0.05). L-NMMA also caused modest blunting of the mixed amino acid-induced hyperfiltration (18 +/- 4 versus 30 +/- 4%, L-NMMA versus vehicle; P = 0.056) but failed to curtail the renal hyperemia (16 +/- 6 versus 20 +/- 4%). Dextrose had no effect on glomerular filtration rate or renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1988

Earliest enamel deposits of the rat incisor examined by electron microscopy, electron diffraction, and electron probe microanalysis.

In order to describe initial events in enamel mineralization and to help characterize inorganic-organic interactions in this tissue, the earliest rod and interrod enamel in mandibular incisors from normal young adult (100 gm) rats, perfused with 100% ethylene glycol, has been studied by transmission electron microscopy, selected area electron diffraction, and high-spatial-resolution electron probe microanalysis. Diffraction and probe data were correlated precisely from the same extracellular regions of the tissue. Sites were examined progressively as a function of location a) from the most recently deposited enamel adjacent to ameloblasts toward the dentin-enamel junction and b) from the apical portion of the tooth longitudinally toward its incisal end. Electron diffraction patterns consistent with that of a poorly crystalline hydroxyapatite were generated at all locations. Diffraction characteristics changed only slightly toward that of more crystalline hydroxyapatite at different locations. Earliest apical enamel generated molar Ca/P ratios in a range of 0.99-1.46 (average 1.24 +/- 0.15). Molar Ca/P ratios of the first enamel interrod elements increased from approximately 1.24 at ameloblast-enamel boundaries to approximately 1.40 at the dentin-enamel junction, small changes corresponding to those observed in electron diffraction characteristics.

Animals↗

PubMed1985

A quantitative microprobe analysis of elements in cortical and nuclear cells of the calf lens.

The outer cortical cells in the calf lens remain transparent under conditions that produce opacity in central nuclear cells. The nuclear cells opacify by a mechanism of cellular restructuring that is associated with a cytoplasmic phase separation while cortical cells do not opacify by this mechanism. In this study the differences in elemental composition of nuclear and cortical cells were analyzed using X-ray emission spectroscopy (XES) of tissue that was prepared for scanning electron microscopy. It was necessary to develop special methods of fixation and dehydration to prevent significant distortion of lens tissue and minimize solubilization and redistribution of elements during the histological processing of the tissue. We calibrated the microprobe for the quantitative analysis using gelatin standards which contained known concentrations of sulfur, potassium, phosphorus, chlorine, and cesium. The standard curves were used to determine proportionality constants, which related the intensity of X-ray emission to the molar concentration of each element, and to determine the minimum detectable levels of each element. An important finding is that the intensity of the X-ray emission is dependent on sample density only at low protein concentration. At the high protein concentrations that exist in lens, the intensity is not affected by sample density.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Single bovine enamel particles examined by electron optics.

Whole enamel scrapings from teeth of embryonic calves have been separated by density gradient centrifugation in organic solvents into fractions (1.6 less than p less than 2.4 g/cm3) representing progressive stages of mineral phase maturation. Single enamel particles or their small aggregates from such fractions were examined by transmission electron microscopy, electron diffraction, and high-spatial-resolution electron probe micro-analysis. The electron optical methods demonstrated the presence of poorly crystalline hydroxyapatite as the only detectable solid phase in all fractions. Octacalcium phosphate and brushite were not identified in the fractions. Changes in electron diffraction patterns were indicative of a progressive increase in apatite crystallinity with enamel maturation. Molar Ca/P ratios were found to range from 1.48 to 1.70, with a higher mean value obtained for lower-density fractions (p less than 2.0 g/cm3). Lower-density fractions contained some particles with high ratios (approximately equal to 2.0-4.0) and a non-uniform distribution of Ca and P, as revealed by electron probe mapping. These characteristics are suggested as possibly being related to carbonate phases in early enamel.

Animals↗

PubMed1983

Phase separation and lens cell age.

Using laser light scattering spectroscopy, we are studying age-related changes in the microstructure of lens cytoplasm. We have established in animal models that one of the earliest identifiable stages in cataract development is the presence of a phase transition in the lens cytoplasm. As a result of the phase transition, the cytoplasm separates into microvolumes that differ in their protein concentration. These microvolumes scatter light and cause the lens to become opaque. This phase separation occurs in normal lens cells at a characteristic temperature, Tcat, which varies across the lens with the cell age. As the animal becomes older, the Tcat for the nuclear cells decreases to a value well below body temperature. In X-irradiated eyes, however, Tcat increases with animal age until the phase separation occurs at or near body temperature. At this point, a well-developed nuclear cataract appears. We are now attempting to understand the biochemical basis for the differences between Tcat of normal and Tcat of X-irradiated lens cells during the aging process.

Aging↗