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S M Shea

Publications and source records attributed to S M Shea.

35 records · Page 2Linked to original sources
PubMed1980

Ultrastructure of the glomerular basement membrane of rats with proteinuria due to subtotal nephrectomy.

Subtotal nephrectomy in the rat gives rise to progressive proteinuria, glomerular hypertrophy, and glomerulosclerosis. The proteinuria antedates significant ultrastructural lesions demonstrable by conventional techniques; its mechanism is obscure. In this article it is shown that proteinuria in this system is not accompanied by evident changes in the ultrastructural distribution of anionic sites in the glomerular basement membrane, as determined by organ perfusion with two cationic probe molecules. It is suggested that the proteinuria may reflect a change in the steric aspect of glomerular ultrafilration, in which the loss of renal mass imposes a significant rise in capillary pressure in a structure whose capillaries are peculiar in the high pressures they normally sustain and in their lack of mechanical support from the interstitium. It is suggested that a sustained rise in capillary pressure overcomes the rigidity of the glomerular basement membrane, so that its pore size increases and proteinuria results from basement membrane failure.

Animals↗
PubMed1979

Humoral inhibitors of the immune response in uremia. II. Further characterization of an immunosuppressive factor in uremic serum.

The serum of Lewis rats with chronic renal insufficiency (induced by subtotal nephrectomy) contains a nondialyzable inhibitor of the mixed lymphocyte reaction. Fractionation of uremic serum by gel filtration on Sephadex G-200 shows that the inhibitory activity elutes with an apparent molecular weight of greater than 200,000 daltons. To establish the possible relationship of the uremic inhibitor to known immunosuppressive components of normal serum, uremic serum was further fractionated on a DEAE cellulose column. The inhibitory activity elutes in 10 mM sodium phosphate at pH 8.0. This fraction contains both alpha-macroglobulin and IgG. The inhibitory activity of this fraction is completely inactivated by treatment with 2-mercaptoethanol, indicating that the inhibitor is a protein. The inhibitory activity is partially inactivated by periodate treatment, suggesting that it may be a glycoprotein. To determine whether or not the inhibitory factor is an immunoregulatory alpha-macroglobulin, or an immune complex, the uremic serum was fractionated by affinity chromatography procedures, which do not induce artifactual inhibitory properties in control serum. The alpha-macroglobulin was removed by affinity chromatography on a column of Con A-Sepharose; its removal had no effect on the inhibitory activity of serum in the mixed lymphocyte reaction. To examine the possibility that immune complexes may be the uremic inhibitor, the serum was fractionated by affinity chromatography on Protein A-Sepharose or by adsorption to a suspension of Staphylococcus aureus, cowan I. Neither of the two latter procedures had any effect on the inhibitory activity of uremic serum. So far all of our findings indicate that the immunosuppressive factor of uremic serum is distinct from two major immunoregulatory factors, alpha-macroglobulin and immune complexes.

Animals↗
PubMed1978

A stereologic study of glomerular hypertrophy in the subtotally nephrectomized rat.

Subtotal nephrectomy in the rat is followed by glomerular hypertrophy, glomerulosclerosis, and, ultimately, renal failure. To gain more insight into this sequence, we have made a morphometric study of the glomerular changes following subtotal nephrectomy in the rat during the period of functional compensation before glomerulosclerosis appears. We found a twofold increase in glomerular volume as compared with controls 2 weeks after operation (to approximately 2 X 10(6) cu mu) followed by a linear increase to approximately 5 X 10(6) cu mu at 21 weeks. The rate of increase in glomerular volume in controls did not significantly exceed that of body weight. The volume increase after subtotal nephrectomy is a true hypertrophy, since other morphometric parameters expressed per unit glomerular volume (surface and length densities) were approximately 80% of control values at 2 weeks and constant thereafter. Glomerular hypertrophy up to 21 weeks is accompanied by a stable BUN and a gradually increasing proteinuria. We conclude that glomerular hypertrophy in this system is a pathologic rather than a compensatory process and suggest that it may represent a counter-productive response to hemodynamic changes serving to increase the glomerular filtration rate.

Animals↗
PubMed1975

A stereological study of the glomerular filter in the rat. Morphometry of the slit diaphragm and basement membrane.

Kidney from normal male albino rats, of body weight 170-200 g, was fixed by arterial perfusion with buffered tannic acid-glutaraldehyde, and postfixed with osmium tetroxide. Random and isotropic ultrathin sections from 23 different glomeruli from five rats were mounted on slot grids for staining and electron microscopy. Prints of whole glomeruli at a magnification of 3,909 were analyzed by stereological methods. The mean glomerular volume was (8.048 +/- 0.474) X 10(5) mum3 if the glomeruli are treated as spheres. The area of the basement membrane was 0.281 +/- 0.017 mm2 per glomerulus, of which 0.184 +/- 0.011 mm2 represents peripheral basement membrane. The aggregate epithelial slit length per glomerulus was 65.19 +/- 3.84 cm, of which 48.69 +/- 2.87 cm represents epithelial slits abutting on the peripheral basement membrane. Assuming that a slit diaphragm is 390 A wide, and that the pores of the slit diaphragm represent 26% of its area, the mean pore area is 3.96 cm2, of which 2.96 cm2 represents the area of peripheral pores. These findings are discussed in the context of the hydrodynamic theory of glomerular ultrafiltration. We conclude that the porous substructure of the glomerular slit diaphragm is significant in determining the hydraulic conductivity of the glomerulus and hence also solute flux during ultrafiltration.

Animals↗
PubMed1971

Lanthanum staining of the surface coat of cells. Its enhancement by the use of fixatives containing Alcian blue or cetylpyridinium chloride.

Among the techniques which have been reported to stain the surface coat of cells, for electron microscopy, is lanthanum staining en bloc. Similarly, the presence of the cationic dye, Alcian blue 8GX, in a primary glutaraldehyde fixative has been reported to improve the preservation of the surface coat of cells of many types; however, the preserved coat is not very electron opaque unless thin sections are counterstained. The present paper shows that for several rat tissues lanthanum staining en bloc is an effective electron stain for the cell surface, giving excellent contrast, if combined sequentially with prefixation in an aldehyde fixative containing Alcian blue. The cationic substance cetylpyridinium chloride was found to have a similar effect to that of Alcian blue in enhancing the lanthanum staining of the surface coat material of the brush border of intestinal epithelial cells. The patterns of lanthanum staining obtained for the tissues studied strikingly resemble those reported in the literature where tissues are stained by several standard methods for demonstrating mucosubstances at the ultrastructural level. This fact and the reproduction of the effect of Alcian blue by cetylpyridinium chloride constitute a persuasive empirical argument that the material visualized is a mucopolysaccharide or mucopolysaccharide-protein complex.

Aldehydes↗
PubMed1969

Endothelial contraction induced by histamine-type mediators: an electron microscopic study.

Previous work has shown that endogenous chemical mediators, of which histamine is the prototype, increase the permeability of blood vessels by causing gaps to appear between endothelial cells. In the present paper, morphologic and statistical evidence is presented, to suggest that endothelial cells contract under the influence of mediators, and that this contraction causes the formation of intercellular gaps. Histamine, serotonin, and bradykinin were injected subcutaneously into the scrotum of the rat, and the vessels of the underlying cremaster muscle were examined by electron microscopy. To eliminate the vascular collapse induced by routine fixation, in one series of animals (including controls) the root of the cremaster was constricted for 2-4 min prior to sacrifice, and the tissues were fixed under conditions of mild venous congestion. Electron micrographs were taken of 599 nuclei from the endothelium of small blood vessels representing the various experimental situations. Nuclear deformations were classified into four types of increasing tightness (notches, foldsl closing folds, and pinches. In the latter the apposed surfaces of the nuclear membrane are in contact). It was found that: (1) venous congestion tends to straighten the nuclei in al groups; (2) mediators cause a highly significant increase in the number of pinches (P < 0.001), also if the vessels are distended by venous congestion; (3) fixation without venous congestion causes vascular collapse. The degree of endothelial recoil, as measured by nuclear pinches, is very different from that caused by mediators (P < 0.001). (4) Pinched nuclei are more frequent in leaking vessels, and in cells adjacent to gaps (P < 0.001); (5) mediators also induce, in the endothelium, cytoplasmic changes suggestive of contraction, and similar to those of contracted smooth muscle; (6) there is no evidence of pericyte contraction under the conditions tested. Occasional pericytes appeared to receive fine nerve endings. Various hypotheses to explain nuclear pinching are discussed; the only satisfactory explanation is that which requires endothelial contraction.

Animals↗
PubMedDate not supplied

Chronic reduction of renal mass: glomerular morphometry by electron microscopy.

Changes of glomerular volume in rats were measured up to 21 weeks following subtotal nephrectomy, using morphometric methods. A linear increase of glomerular volume was observed between 2 and 21 weeks after subtotal nephrectomy. This progressive increase in glomerular volume may reflect compensatory hemodynamic changes leading to an increased single nephron glomerular filtration rate.

Animals↗