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D Alcorn

Publications and source records attributed to D Alcorn.

At least 73 records · Page 4Linked to original sources
PubMed1991

Immunohistochemical detection of parathyroid hormone-related protein in human fetal epithelia.

PTH-related protein (PTHrP) is commonly produced by squamous cell carcinomata and is the mediator of the PTH-like features of humoral hypercalcemia of malignancy. It has also been implicated in calcium regulation during fetal development. In this study immunohistochemical techniques, using rabbit polyclonal antibodies to synthetic PTHrP peptides, have been used to localize PTHrP in human fetal tissues from one fetus of 7 weeks and two of approximately 18 and 20 weeks gestation, respectively, in order to identify sites of potential functional significance. PTHrP immunoreactivity was identified in epithelia from many sources, including skin, bronchus, pancreas, pharynx, gut, stomach, and renal pelvis. Thyroid and parathyroid glands, which develop from epithelial origins, also stained positive for PTHrP, as did kidney collecting tubules, adrenal tissue, and skeletal and smooth muscle. PTHrP immunoreactivity was also located in developing long bones and calvaria, where it may have relevance in bone turnover during fetal development. The role of PTHrP at these locations remains to be elucidated, but the identification of specific PTHrP immunoreactivity in fetal epithelia is consistent with PTHrP production by cancers of epithelial origin and supports the hypothesis that PTHrP may have a role in epithelial growth and differentiation.

Bronchi↗
PubMed1990

Congenital hypertrophy of the retinal pigment epithelium predicts colorectal polyposis in Gardner's syndrome.

We studied prospectively the utility of congenital hypertrophy of the retinal pigment epithelium as a predictor of colonic polyposis in offspring of patients with familial adenomatous polyposis with extracolonic manifestations (Gardner's syndrome). After they underwent initial indirect ophthalmoscopy, we followed up 34 individuals at 50% genetic risk for familial adenomatous polyposis with extracolonic manifestations due to an affected parent. All 34 obtained their first colorectal endoscopic examination during a follow-up period of up to 4 years. The 16 individuals who did not have congenital hypertrophy of the retinal pigment epithelium (aged 13 to 40 years; mean, 25 years) remained polyp free, while 14 of 18 individuals with congenital hypertrophy of the retinal pigment epithelium (aged 9 to 30 years; mean, 18 years) were found to have colorectal adenomatous polyposis. Our findings indicate that the presence of multiple patches of congenital hypertrophy of the retinal pigment epithelium in children and young adults at risk for familial adenomatous polyposis with extracolonic manifestations is a clinically useful predictor of colorectal polyposis.

Adenomatous Polyposis Coli↗
PubMed1990

Qualitative and quantitative analysis of granules in atrial appendage cardiocytes in different physiological states.

Atrial appendage cardiocytes of mammals, including man, contain multiple cytoplasmic granules that vary in number in different physiological states. Using morphologic and comprehensive morphometric techniques, these granules were assessed in Sprague-Dawley rats following dehydration for 5 days, volume-loading by substituting 1% NaCl as drinking water for 7 days, unilateral nephrectomy plus volume-loading for 7 days, and in late term pregnant animals (18-20 days; term approximately 21 days). Although principally located in the paranuclear region, granules were observed throughout the sarcoplasm. Cytological features indicative of synthetic activity and granule formation were readily apparent in all groups with the exception of pregnant rats where they were infrequently observed. Granule contents were released by exocytosis and observed in the right appendage of control, dehydrated and nephrectomy/volume-loaded groups and left appendage of volume-loaded animals. Exocytosis was not observed in pregnant animals. By point counting, the proportional volume of cardiocytes occupied by granules (Vv) in controls was significantly greater for right than for left appendage (2.12 +/- 0.22% vs 1.29 +/- 0.16%; mean +/- SEM; p less than 0.05). A significantly similar difference was found for nephrectomy/volume-loaded animals. There was no significant difference in Vv for right appendage between the control and experimental groups; for left appendage there was a significant increase in Vv to 2.42 +/- 0.09% (p less than 0.05) for volume-loaded animals only. Estimation of the maximum diameter of granule profiles in control animals was 238 +/- 9 nm and 230 +/- 6 nm for right and left appendages, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Granular juxtaglomerular cells and prorenin synthesis in mice treated with enalapril.

The short-term and long-term effects (for up to 98 days) of the angiotensin converting enzyme inhibitor enalapril were investigated in male and female BALB/c mice. In control animals, separate antisera to renin and its prosequence produced an identical pattern of staining in granular cells of the juxtaglomerular apparatus (JGA) a short distance from the glomerulus. After 1 day of the enalapril treatment there was a decrease in the number of JGA granular cells immunostained with antisera to both renin and its prosequence. Electron microscopy revealed degranulation of mature granules from JGA granular cells. Fusion of granules with the cell membrane was not observed, but numerous membrane-like structures (myelin figures) were identified in the cytoplasm and extracellular space, indicating possible secretion. In addition, the volume proportion of granulated cells in relation to the glomerular volume was decreased, as was renal renin content. With continuing enalapril treatment, separate antisera to renin and its prosequence stained the same granulated JGA cells with equal intensity. The cells so stained increased in number, extending down the wall of the afferent arteriole to cortical radial arteries (interlobular arteries) upstream from the glomerulus. Ultrastructural studies revealed a progressive development of cytoplasmic granulation in JGA granular cells and in smooth muscle cells extending into cortical radial arteries. Furthermore, the volume proportion of granulated cells in relation to the glomerular volume was significantly increased, as was renal renin content. Thus, short-term enalapril treatment in mice provoked rapid secretion of renin via degranulation of mature granules from JGA granular cells. In contrast, long-term enalapril treatment produced a continuing stimulus for renin synthesis, secretion and storage, resulting in an increased thickness of the afferent arteriolar wall. The mechanism for this change appears to be hypertrophy and hypergranulation of granular JGA cells and neogranulation of smooth muscle cells upstream from the glomerulus. Identification of the intrarenal mediators that induce these phenotypic changes presents an interesting challenge.

Animals↗
PubMed1990

Angiotensin II and the maintenance of GFR and renal blood flow during renal artery narrowing.

The time course of the renal blood flow and GFR responses to narrowing of the renal artery in conscious dogs is reviewed. The initial response to this threat to renal perfusion is renal vasodilatation, but within minutes a secondary vasoconstriction mediated by angiotensin II begins to develop. Angiotensin II-mediated contraction of mesangial cells is also demonstrable, but this does not apparently reduce the filtration surface area of the glomerular capillaries. The intrarenal effects of angiotensin II restore GFR back to normal within one to two weeks, by which time circulating plasma angiotensin II levels are no longer elevated. In contrast to its effects on GFR, angiotensin II has minimal effects on renal blood flow after stenosis. This may be because, (i) blood flow is mainly determined by the hydraulic resistance of the stenosis; (ii) renal vasoconstriction has relatively little effect on flow due to the particular hemodynamic properties of the stenoses, and (iii) a major site of action of angiotensin II may be within the glomerulus. Thus angiotensin II has a homeostatic role in the maintenance of GFR during renal artery narrowing and one component of this role may involve mesangial contraction.

Angiotensin II↗
PubMed1989

Glomerular actions of ANG II during reduction of renal artery pressure: a morphometric analysis.

The glomeruli of kidneys subjected to reduced perfusion pressure were examined morphometrically. The left renal artery was narrowed for 30 min in anesthetized dogs with (n = 6) or without (n = 7) converting-enzyme inhibition (captopril). The kidneys were then rapidly fixed by glutaraldehyde perfusion at high flow rate. In a comparison of glomeruli of kidneys subjected to pressure reduction in captopril-treated and untreated dogs, there was significantly greater mesangial contraction in the latter, but morphometric analysis revealed no significant differences in the glomerular surface area available for filtration as evidenced by glomerular capillary volume fractions, surface areas of the filtering basement membrane between epithelial and endothelial cells, or the length densities of the glomerular epithelial slits. In a comparison of the left (pressure reduction) and right (no pressure reduction) kidneys in the captopril-treated dogs, there was no significant effect of reduction of renal perfusion pressure per se on mesangial contraction or glomerular filtration surface area when angiotensin (ANG) II formation was blocked. Thus ANG II caused mesangial cell contraction after renal artery stenosis, but this did not significantly change glomerular ultrafiltration surface area.

Angiotensin II↗
PubMed1989

Effect of converting enzyme inhibition on renin synthesis and secretion in mice.

We have investigated the relative importance of renal renin stores and de novo synthesis during stimulation of renin secretion and the role of transcription and posttranscriptional factors in providing increased synthesis of renin. When enalapril was administered to previously untreated mice, plasma renin concentration increased 40-fold within 1.5 hours, and remained at a high level for the 8 days of the experiment. Renal renin decreased by 82% after 24 hours and thereafter increased to levels higher than controls. Calculations of renin turnover, based on data for the rate of metabolism of renin in plasma, indicated that most of the renin released in the first 24 hours could be accounted for by the decrease in renal renin stores, indicating that de novo synthesis played only a minor role. After 24 hours, however, when both plasma renin concentration and renal renin increased, the calculated rate of renin synthesis increased to nearly 40 times the rate in controls. When enalapril was administered to mice that had been depleted of plasma and renal renin by chronic sodium loading, plasma renin concentration increased markedly within 1.5 hours, but to only half the level achieved in the previously untreated mice. No decrease in renal renin occurred, suggesting that the renal renin remaining after chronic sodium loading was not available for release. Renal renin messenger RNA increased 4.5-fold after 6 hours, and after 8 days had increased to 5.0 times the level at day 0. The increase in calculated rate of renin synthesis was maximal between 5 and 8 days, when it was 54 times greater than at day 0. During enalapril treatment, there were marked increases in the granulation of the juxtaglomerular cells and in the amount of rough endoplasmic reticulum and Golgi apparatus they contained. These results suggest that posttranscriptional factors play a major role in determining the rate of renin synthesis.

Analysis of Variance↗
PubMed1989

Immunohistochemical study of peripolar cells of the sheep.

The proposal that the cytoplasmic granules of glomerular peripolar cells (PPCs) of the adult sheep and lamb contain a kallikrein-like substance has been re-examined. After extensive characterisation and purification of anti-kallikrein antibodies, it was concluded that PPCs do not contain immunohistochemically detectable amounts of urinary kallikrein; nor do such cells appear to synthesise kallikrein as shown by hybridisation histochemistry studies. They are also not renin-immunopositive. On the other hand, a proportion of them exhibit neuron-specific enolase (NSE) immunoreactivity, unlike the apparently closely related visceral and parietal epithelial cells.

Animals↗
PubMed1987

Intercellular spaces between macula densa cells: an ultrastructural study comparing high pressure perfusion fixation with in situ drip-fixation of rat kidney.

In situ drip-fixation of superficial glomeruli and tubules in the rat kidney verified the results obtained from high pressure perfusion fixation studies indicating that distinct spaces normally exist between the cells of the macula densa. Following treatment with frusemide these intercellular spaces between the macula densa cells became closed in both drip-fixed and perfusion-fixed kidneys. These findings suggest that the variability of extracellular compartmentation found in the macula densa is unlikely to be an artifact but most likely represents changes in the in vivo status of the macula densa.

Animals↗
PubMed1987

Angiotensin II-induced contraction of mesangial cells in acute renal artery stenosis in dogs.

1. Renal artery stenosis was induced in anaesthetized dogs, and the kidney rapidly fixed after 30 min. 2. Electron microscopy revealed marked folding of the paramesangial basement membrane in stenotic kidneys (n = 7). The extent of this folding was significantly less in dogs treated with captopril (n = 6). 3. It is suggested that this folding reflects angiotensin II-induced contraction of the mesangial cells, which may help maintain glomerular filtration rate following stenosis.

Angiotensin II↗
PubMed1987

Renal actions of angiotensin II in renovascular hypertension.

In renal artery stenosis severe enough to cause hypertension, angiotensin II maintains glomerular filtration rate (GFR) both in the initial high renin phase of hypertension and later when plasma levels are normal. Angiotensin II also maintains GFR in less severe stenosis, which does not cause hypertension. This homeostatic action of angiotensin II to maintain GFr has minimal effects on blood flow. In renal-wrap hypertension, plasma renin levels are elevated for longer than after renal artery stenosis, but in other respects this initial phase of the hypertension is similar to that after renal artery stenosis. GFR is reduced, the rate of development of hypertension is accelerated by angiotensin II, and angiotensin II maintains the glomerular filtration fraction. Renal resistance is markedly increased owing to both compression of the kidney by the hypertrophying renal capsule and to angiotensin II. Thus angiotensin II apparently plays a primarily homeostatic role in renovascular hypertension to maintain glomerular ultrafiltration. It is suggested that the angiotensin II may be formed intrarenally and may act on sites other than resistance blood vessels.

Angiotensin II↗
PubMed1986

Distribution of glomerular peripolar cells in different mammalian species.

Peripolar cells are granulated glomerular epithelial cells that form a cuff around the vascular pole of the glomerulus. Quantitation of these cells in 17 species of mammals (including man, several laboratory animals and a variety of other species) indicated that they were detectable by light microscopy in all but one of the mammals that were examined (the Australian hopping mouse). In adult mammals with detectable peripolar cells, the "peripolar cell index" (the percentage of randomly sectioned glomeruli that displayed peripolar cells in histological sections of kidney) ranged from 0.15 (for echidna) to 11.86 (for sheep). Newborn lambs and rats showed strikingly high values (23.30 and 10.76, respectively) compared with their adult counterparts. Using electron microscopy, peripolar cells were observed in all species that were examined, including the Australian hopping mouse. Morphologically, peripolar cells were similar in all species although their size and granule population varied. They showed a predominantly outer cortical glomerular distribution and a close anatomical relationship with the renin-containing myo-epithelioid cells. These findings indicate that peripolar cells are present in a wide variety of species and support the view that such cells may play a significant role in the regulation of normal renal function.

Aging↗
PubMed1986

Effect of sodium intake and sodium delivery to the macula densa on renal renin content and juxtaglomerular apparatus morphology.

Active and inactive renin were measured in individual juxtaglomerular apparatus (JGA) and in whole kidney homogenates. The morphology of the JGA was examined in microbiopsy glomerular specimens and in kidneys fixed by arterial perfusion. In rats on high and normal salt intake the total renin content of a single JGA was 14 (s.e.m. = 3) and 29 (s.e.m. = 4) ng AI/h, respectively. The amount of cystoplasm occupied by renin granules was 20% and 27%. Crystalline cores were seen in 1.5% and 7% of the granules, respectively. Increased delivery of NaCl to the macula densa did not alter total renin, but decreased inactive renin from 30% to 0, crystalline core-containing cells from 33% to 14% and decreased the percentage of granules with crystalline cores from 12% to 2.2%. Increased sodium in the diet and increased delivery of NaCl to the macula densa decreased the proportion of renin present in the inactive form and decreased the proportion of crystalline cores. These coincidental alterations suggest that crystalline cores contain inactive renin and suggest that the delivery of sodium to the macula densa activates renin.

Animals↗
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↗