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Biomedical subjects

G B Ryan

Publications and source records attributed to G B Ryan.

At least 55 records · Page 3Linked to original sources
PubMed1986

Morphological changes in the renal macula densa during natriuresis and diuresis.

Morphological changes in the macula densa have been studied during the infusion of diuretic agents into the renal artery of anesthetized dogs. The kidneys were fixed by rapid high pressure perfusion with glutaraldehyde. Large basolateral intercellular spaces were seen between macula densa cells in control kidneys, but the number and extent of these spaces were strikingly reduced during the natriuresis and diuresis induced by the infusion of frusemide, ethacrynic acid or mannitol. Natriuresis and diuresis produced by the intravenous infusion of large volumes of 0.9% NaCl solution also resulted in closure of these spaces. No simple relationship existed between changes in plasma renin activity and closure of the spaces between macula densa cells during these procedures. A distinctive, membrane-bound, vesicle-containing structure was identified between the basolateral processes of the cells of each macula densa; the function of this structure awaits elucidation. We suggest that changes in the size of the basolateral intercellular spaces of the macula densa reflect changes in fluid flux between the distal tubule and the interstitium of the juxtaglomerular apparatus.

Animals↗
PubMed1986

The role of the macula densa in renin release: studies by microperfusion.

The role of the macula densa in control of renin release and in mediation of tubulo-glomerular feedback was investigated following orthograde microperfusion in Munich Wistar rats. Tubules of surface glomeruli were perfused, drip-fixed with glutaraldehyde and biopsy cores taken containing perfused and non-perfused glomeruli. Serial sections were examined by light and electron microscopy. In some animals dilated basolateral spaces were observed between cells in control maculae densa but no spaces were found following microperfusion with hypertonic NaCl, isotonic mannitol or hypotonic NaCl containing 1 mg/l frusemide. In other animals no spaces were found in control cores, and perfusion with the above solutions had no effect. However, in such animals, tubules perfused with hypotonic NaCl (71 mmol/kg H2O) had prominent basolateral spaces in their maculae densa. The presence of dilated basolateral intercellular spaces is generally associated with osmotically driven water flow. The extent of dilatation of such spaces in the macula densa is correlated with transepithelial osmotic or ionic gradients and may indicate activity of these cells in the recognition of distal tubular fluid composition.

Animals↗
PubMed1985

Uptake of circulating hyaluronic acid by the rat liver. Cellular localization in situ.

The uptake of [3H]acetyl-labelled hyaluronic acid (HA) was examined in the liver, spleen and kidney of the rat after i.v. injection. 3H-activity was located by light- and electron-microscopic autoradiography after measurement by scintillation counting of tissue digests. In the liver, approximately 90% of the radioactivity was located in the sinusoidal endothelial cells, with autoradiographic grains distributed throughout the cytoplasm; 50% of the grains overlay vacuoles 0.3 to 1.2 micron in diameter. A few grains (4%) were located in Disse's space or nearby in the cytoplasm of hepatocytes. No grains were found in Kupffer cells. The remainder were randomly scattered across the sections in a pattern indicating nonspecific background activity. These observations are in accordance with the selective uptake of HA exhibited by dissociated liver cells in vitro. HA concentrations in the spleen and kidney were too low for detection by autoradiography. Splenic concentrations were much lower than in rabbits or mice; in this respect the uptake of circulating HA in the rat resembles that reported for chondroitin 4-sulphate.

Animals↗
PubMed1985

Renin gene expression in vessels of the ovine renal cortex.

Using hybridization histochemistry, a technique which localizes specific mRNA populations in tissue sections with a 700 base pair recombinant DNA probe which codes for ovine renin, we have localized renin gene expression in the afferent arteriole of the juxtaglomerular apparatus (JGA) in the sheep renal cortex. Specific labelling representing renin gene expression was also found at a distance from the glomerular tuft in the walls of the afferent arteriole and also in cells in the medial layer of larger vessels of the renal cortex, specifically the interlobular arteries. These observations provide morphological evidence of renin gene expression at these sites and, combined with ultrastructural and immunocytochemical evidence suggest that renin is synthesized and stored in the afferent arteriole either within the JGA or at a distance from the glomerulus, and in the smooth muscle coat of the interlobular arteries in the sheep kidney.

Animals↗
PubMed1985

A comparison of the avascular capsule surrounding free floating intraperitoneal blood clots in mice and rabbits.

The development of the avascular fibrous capsule which surrounds free floating intraperitoneal blood clots in mice and rabbits is described. In mice, the capsule at 2 wk consisted of an outer layer of partially flattened macrophage-like cells overlying a thick layer of myofibroblasts embedded in a collagenous stroma. In contrast, in rabbits the capsule at 2 wk consisted of 3 distinct layers: an outer layer of mesothelial cells; an underlying relatively acellular layer containing a few macrophages; and, immediately adjacent to the clot, an innermost layer of variable thickness consisting mostly of myofibroblasts. The myofibroblasts of the rabbit capsule were fewer in number than those of the mouse. Detailed examination of the formation of these capsules suggests that myofibroblasts may develop from cells within the peritoneal cavity that show morphological features characteristic of monocytes/macrophages.

Animals↗
PubMed1985

Glomerular podocytic injury in protein overload proteinuria.

Injection of rats with large doses of bovine serum albumin causes proteinuria which may persist long after the period of overload has ended. In order to assess in this model of proteinuria the relative importance of podocytic epithelial changes versus alterations in anionic groups in the glomerular capillary wall a morphological study has been made of animals in which the kidneys were fixed by vascular perfusion or by in situ drip fixation. By transmission electron microscopy, podocytes showed protein droplets, cytoplasmic vacuoles, spreading of epithelial cytoplasm with loss of foot processes, and focal separation of epithelium from the glomerular basement membrane, occasionally with cytoplasmic disruption. Staining with colloidal iron showed no reduction in the density of anionic groups per unit area on epithelial cell surfaces or elsewhere in glomeruli. However, the reduced surface area of epithelial cells caused by the changes to their structure accounts adequately for the less intense glomerular colloidal iron staining evident by light microscopy. Changes in podocyte structure, particularly those leading to focal cytoplasmic defects on the outer surface of the glomerular basement membrane, appear to be more important than loss of glomerular anionic groups for the development of proteinuria in protein overload nephropathy.

Animals↗
PubMed1984

Functional and morphologic studies of the adrenal cortex and kidney in ovine toxaemia of pregnancy.

Functional and morphologic studies of the adrenal cortex and kidney have been carried out in pregnant sheep with spontaneous or dietary restriction-induced ovine toxaemia. It was found that proteinuria was an inconstant feature and no animal showed glomerular lesions analogous to those found in human preeclampsia; thus ovine toxaemia cannot be regarded as a precise experimental model for human toxaemia of pregnancy. The elevation of blood cortisol levels and the morphologic appearance of the adrenal zona fasciculata found in such animals suggest an adrenal response comparable to that caused by adrenocorticotrophic hormone. In addition, animals with severe disease showed evidence of stimulation of the renin-angiotensin-aldosterone system as reflected by elevated blood renin and aldosterone concentrations and raised renal juxtaglomerular indices. Ultrastructural changes in the adrenal zona glomerulosa and renal juxtaglomerular myoepithelioid cells in toxaemic animals resembled those described in non-pregnant sodium-depleted sheep. The finding of juxtaglomerular peripolar cell mitoses and granule exocytosis, the latter only being previously observed in sodium depleted sheep, together with the ultrastructural changes in the adrenal zona glomerulosa and juxtaglomerular myoepithelioid cells, suggest that sodium depletion may play a role in this disease.

Adrenal Cortex↗
PubMed1984

Peripolar cell hypertrophy in the renal juxtaglomerular region of newborn sheep.

In the renal juxtaglomerular region of newborn sheep, it was found that glomerular peripolar cells and their granules were very much larger than those found in fetal lambs or adult sheep. Similar peripolar cell hypertrophy was triggered in fetal lambs treated in utero with intraperitoneal injections of dexamethasone. Ultrastructurally, granules of peripolar cells from newborn lambs resembled closely the enlarged zymogen granules described in the pancreas of newborn rats. Such peripolar cell hypertrophy may reflect a functional adaptation of the kidney to immediate postnatal life.

Animals↗
PubMed1984

Structural and functional studies of the adrenal cortex and renal juxtaglomerular apparatus in pregnant sheep subjected to sodium depletion or loading.

The morphological changes in the adrenal cortex and renal juxtaglomerular apparatus have been examined in pregnant sheep subjected to sodium depletion or loading. These changes were similar to those found in non-pregnant sheep in response to sodium depletion or loading, with the additional finding of interstitial edema in the zona glomerulosa of sheep with twin fetuses. As in non-pregnant sheep, sodium depletion resulted in evidence of juxtaglomerular peripolar cell granule release. The major finding was that sodium depletion in sheep with twin fetuses triggered the onset of ovine toxemia or "twin lamb disease".

Adrenal Cortex↗
PubMed1983

Origin of glomerular crescents in rabbit nephrotoxic nephritis.

The origin of glomerular crescents was investigated in an accelerated model of rabbit nephrotoxic nephritis. In rabbits immunised against sheep gamma-globulin, the administration of sheep nephrotoxic serum provoked cellular crescent formation affecting 30 to 90 per cent. of glomeruli at 6 days. The crescents were composed predominantly of cells with ultrastructural features of macrophages. In animals depleted of circulating leukocytes by whole body irradiation, with or without shielding of the kidney, crescent formation was inhibited despite severe glomerular damage and fibrin deposition in Bowman's space. These findings support the hypothesis that glomerular crescents develop principally from the emigration and accumulation of bone marrow-derived mononuclear cells.

Animals↗
PubMed1983

Structural and functional studies of the adrenal zona glomerulosa in sodium-depleted and sodium-loaded sheep.

The effects of alterations in sodium status upon the morphology of the adrenal zona glomerulosa in sheep have been examined qualitatively and quantitatively, using light- and electron microscopy, and correlated with functionally related biochemical data. With severe sodium depletion induced by parotid-cannula drainage, there was mitotic activity throughout the zona glomerulosa, and glandular cells showed striking ultrastructural changes. These changes particularly affected mitochondria, which were enlarged, rounded and showed replacement of their normal lamelliform cristae by thin elongated cristal elements and bundles of tubular "rod-like" structures. Quantitative morphometric studies showed an increase in the volumes of zona glomerulosa cells, nuclei, mitochondria, smooth and granular endoplasmic reticulum, and Golgi profiles. In contrast, with dietary sodium loading, zona glomerulosa cells appeared shrunken and showed cytoplasmic lipid accumulation; mitochondria and other organelles were not significantly altered. The correlation of the ultrastructural cytological alterations in zona glomerulosa cells in sodium-depleted sheep with raised blood aldosterone levels suggests that such morphologic changes reflect a heightened capacity of these cells for aldosterone biosynthesis and secretion. These changes may also account for the increased sensitivity of the zona glomerulosa to aldosterone-producing stimuli during sodium deficiency.

Adrenal Cortex↗
PubMed1983

Structural studies of the adrenal zona glomerulosa and renal juxtaglomerular apparatus in pregnant sheep.

The ultrastructural changes in the adrenal zona glomerulosa and renal juxtaglomerular apparatus have been examined during normal pregnancy in sheep. As pregnancy progressed, increasing numbers of cells in the adrenal zona glomerulosa displayed mitochondria with straight tubular "rod-like" structures replacing their normal lamelliform cristae; groups of cells showing these mitochondrial changes were predominantly located in the middle and superficial regions of the zona glomerulosa, but at all stages remained interspersed with cells with apparently normal mitochondria. In the same animals, the renal juxtaglomerular index was raised, reflecting an increase in renin storage, and juxtaglomerular myoepithelioid cells showed increased numbers of cytoplasmic granules, but no apparent increase in granular endoplasmic reticulum and Golgi profiles; there were no distinguishing morphological changes in juxtaglomerular peripolar cells. These findings provide morphologic evidence of stimulation of the adrenal zona glomerulosa in association with increased juxtaglomerular renin storage during pregnancy. The mitochondrial changes observed in an increasing proportion of cells in the zona glomerulosa closely resemble those seen in sodium-depleted animals, and may reflect the altered steroidogenic capacity of the adrenal gland in pregnant sheep. The finding of groups of cells displaying altered mitochondria lying next to cells with normal mitochondria suggests the presence of cells with different sensitivities to stimuli for aldosterone production or may indicate the presence of different cell types in the zona glomerulosa responding to different stimuli.

Adrenal Glands↗
PubMed1983

Macrophages and glomerular crescent formation. Studies with rat nephrotoxic nephritis.

A model of crescentic glomerulonephritis in the rat was developed, based upon an augmented form of nephrotoxic nephritis. The glomerular lesions were relatively mild, permitting an analysis of the morphologic events in crescent formation to an extent not possible in models in other species in which the sequence of changes is obscured by the severity of the inflammatory process. Monocytes and macrophages accumulated in glomerular capillary lumens and walls. Crescents were composed of cells with ultrastructural features indistinguishable from those of the intracapillary mononuclear cells. The findings support the view that the crescent cells are predominantly composed of macrophages derived from circulating monocytes.

Animals↗
PubMed1983

Origin of myofibroblasts in the avascular capsule around free-floating intraperitoneal blood clots.

The origin of cells comprising the capsule which forms around free-floating intraperitoneal blood clots has been examined in rats. One day after implantation the surface of the clot was covered by 1-2 layers of rounded nucleated cells. The majority of these cells were monocyte/macrophage in type with many cytoplasmic folds. Over the next 2 wk a thick capsule composed of dense connective tissue and myofibroblasts developed, completely covering the clot. The surface became covered by a contiguous layer of mesothelial cells, apparently derived from displaced cells of the damaged peritoneum. Detailed examination of the formation of the capsule suggested that a proportion of cells with the characteristic features of peritoneal macrophages gradually develop over a 3-4 d period the characteristic features of fibroblasts. These cells with time then develop filament bundles and a basal lamina to become myofibroblasts.

Animals↗
PubMed1983

Renal pathology associated with lithium therapy.

Renal biopsies have been examined in patients either currently (50 patients) or previously (5 patients) on maintenance lithium therapy for severe affective disorders. In patients currently taking lithium, a distinctive lesion of the distal convoluted tubules and collecting ducts was identified. This lesion consisted of vacuolation and swelling of the cytoplasm with accumulations of PAS positive material; this material was confirmed to be particulate glycogen by light and ultrastructural techniques. This 'lithium-associated' lesion was not present in patients who had discontinued lithium therapy. Prospective studies showed that the accumulation of glycogen occurs in distal tubules and collecting ducts within days of commencing lithium treatment. The relationship of this distinctive lesion to the patchy focal cortical interstitial fibrosis seen in these biopsies remains to be elucidated.

Adult↗
PubMed1983

Ultrastructural changes in the sheep renal juxtaglomerular apparatus in response to sodium depletion or loading.

The ultrastructural changes in various components of the renal juxtaglomerular apparatus have been examined in sheep subjected to sodium depletion or loading. In normal sheep, juxtaglomerular arteriolar myoepithelioid cell granulation was relatively sparse whereas peripolar cell granulation was prominent. Sheep subjected to rapid sodium depletion in response to parotid cannula drainage showed features indicating increased activity of the renin-angiotensin system with a rise in plasma renin concentration, an increase in the juxtaglomerular index and morphological evidence of increased renin granule production in arteriolar myoepithelioid cells. In contrast, in sheep subjected to dietary sodium loading, there was evidence of decreased activity of the renin-angiotensin system with a fall in plasma renin concentration and relatively poor myoepithelioid cell granulation. In sodium depleted sheep, juxtaglomerular peripolar cells showed increased synthetic activity and marked heterogeneity of granule density; in sodium loaded sheep, peripolar cells showed no consistent changes. A major new finding was the detection of exocytotic release of granule material from peripolar cells into the urinary space during sodium depletion, confirming the secretory nature of such cells and supporting the concept that they may play a role in sodium homeostasis.

Animals↗
PubMed1983

Urinary erythrocyte morphology in the diagnosis of glomerular hematuria.

Urine samples from 141 consecutive patients referred for investigation of microscopic hematuria were examined by phase-contrast microscopy to determine the probable site of bleeding into the urinary tract. Dysmorphic (i.e. morphologically variable) erythrocytes, suggestive of glomerular bleeding, were present in 86 of 87 patients with significant hematuria who were later shown to have glomerulonephritis. In contrast, all of 30 patients with non-glomerular lesions had isomorphic (i.e. morphologically uniform) erythrocytes in the urine. Ten patients yielded a mixed morphologic pattern suggestive of dual pathology which was confirmed in four patients. Urine erythrocyte counts from 376 healthy individuals showed that 95% yielded less than 8,000 cells/ml and in each case erythrocytes exhibited a dysmorphic pattern suggesting that erythrocytes enter the urine of healthy subjects via the glomerulus. Electron microscopy of urinary erythrocytes from 36 patients with glomerulonephritis demonstrated the range of dysmorphic changes characteristic of glomerular bleeding, presumably resulting from environmental changes suffered by the erythrocytes within renal tubules.

Adolescent↗