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D Alcorn

Publications and source records attributed to D Alcorn.

16 recordsLinked to original sources
PubMed1992

Immunohistochemical localization of transthyretin in glomerular peripolar cells of newborn sheep.

Purified transthyretin has been isolated from sheep serum. Antiserum raised against this protein has been used with an indirect immunoperoxidase histochemical technique to identify transthyretin in newborn lamb kidney tissue. Transthyretin was found in proximal tubule cells and in glomerular peripolar cells. Preabsorption studies using purified transthyretin protein indicate that the immunoreactivity of the antiserum is specific to transthyretin.

Animals↗
PubMed1992

Renin processing studied by immunogold localization of prorenin and renin in granular juxtaglomerular cells in mice treated with enalapril.

Immunogold techniques were used to investigate renin processing within granular juxtaglomerular cells following short-term (6 h and 1 day) and long-term (4 weeks) enalapril treatment in female BALB/c mice. In control animals, renin protein labelling was localized to all types of granules (proto-, polymorphous, intermediate and mature) and to transport vesicles, whilst prorenin labelling was found in all these sites except mature granules, confirming that active renin is localized to mature granules only. Following short-term enalapril treatment, the exocytosis of renin protein from mature granules was increased. Long-term enalapril treatment resulted in increased numbers of transport vesicles and all types of granules, consistent with increased synthesis and storage of renin. More large intermediate granules contained discrete regions labelled for prorenin. Renin protein was exocytosed from individual and multiple granules, whilst prorenin was exocytosed from proto- and intermediate granules. It is concluded that under normal conditions prorenin is secreted constitutively by bulk flow from transport vesicles. On the other hand, active renin is secreted regulatively from mature granules. In conditions of intense stimulation (angiotensin-converting enzyme inhibition treatment), increased synthesis of prorenin leads to enhanced secretion of prorenin by both constitutive and regulative pathways. Under these conditions, the conversion of prorenin to active renin is increased, with increased secretion of active renin occurring in a regulative manner. Furthermore, the localization of prorenin to one discrete region of large intermediate granules leads us to conclude, that cleavage of the prosegment of renin occurs with the transition of intermediate to mature granules.

Animals↗
PubMed1992

High resolution localization of angiotensin II receptors in rat renal medulla.

The cellular localization of angiotensin II (Ang II) receptors in the inner stripe of the outer medulla of the rat kidney was investigated by using high resolution light and electron microscopic autoradiography. Fresh tissue blocks from the inner stripe of the outer medulla were incubated with 125I-[Sar1, Ile8] Ang II and prepared for microscopic autoradiography. At the light microscopic level, 125I-[Sar1, Ile8] Ang II was found to penetrate into the tissue and to bind specifically to sites outlining renal tubules and vasa recta bundles. Electron microscopic autoradiography revealed that silver grains were detected over interstitial cells located between the tubules and components of the vasa recta bundles, but no silver grains were detected overlying the cells of the thin descending or thick ascending limbs of the loop of Henle, the collecting ducts, the vasa recta, or other blood vessels. These interstitial cells contained abundant endoplasmic reticulum, microfilaments, occasional lipid droplets and extensive cytoplasmic processes which closely related to the basement membranes of the vasa recta and loops of Henle. The cells therefore closely resemble type 1 interstitial cells. Since Ang II binding sites are absent in the inner medulla, the cells labelled by this technique must be a subset of type 1 interstitial cells, distinct from the typical lipid-laden interstitial cells most abundant in the inner medulla. These findings demonstrate that type 1 interstitial cells are the primary sites for a high density of Ang II receptors located in the inner stripe of the outer medulla.

Animals↗
PubMed1992

Morphometric analysis of the actions of angiotensin II on renal arterioles and glomeruli.

To study the effects of angiotensin II on afferent and efferent arteriole diameters and on intraglomerular dimensions, angiotensin II (20 ng.kg-1.min-1) or saline vehicle was infused intravenously for 20 min into anesthetized rabbits pretreated with enalapril. Both kidneys were perfusion fixed (glutaraldehyde), and vascular casts were made of the right kidneys using methacrylate. Morphometric analysis of the left kidneys using transmission electron microscopy revealed no significant effects of angiotensin II within the glomerulus, including the degree of mesangial contraction. The diameters of the afferent and efferent arteriole casts from the right kidneys were measured at 20, 50, and 75 microns from the glomerulus by scanning electron microscopy. In the outer cortex the mean diameters of the afferent and efferent arterioles were 14.1 +/- 0.8 and 9.7 +/- 0.5 microns, respectively, in the angiotensin II-infused rabbits, significantly less than in the control (vehicle) rabbits, 17.0 +/- 0.7 microns (P less than 0.001) and 10.7 +/- 0.4 microns (P less than 0.005), respectively. Calculation of the relative changes in vascular resistance, however, indicated that the effects of angiotensin II on efferent arteriole resistance (average difference 2.4 +/- 1.2 units/microns) were significantly greater per unit length than the effects on afferent arteriole resistance (average difference 0.9 +/- 0.3 units/microns). Thus infused angiotensin II caused greater reduction in afferent arteriolar diameter than in efferent, but the calculated increase in vascular resistance per micron was greater in efferent vessels due to their smaller resting diameter.

Angiotensin II↗
PubMed1991

The role of the macula densa in renin synthesis.

1. The role of the macula densa in renin synthesis was studied using mice with one hydronephrotic kidney. 2. Renin synthesis was assessed by measurement of renal renin, renal mRNA for renin and plasma renin. 3. Sodium depletion stimulated mRNA and renal renin to a similar extent in the hydronephrotic and contralateral kidney. 4. Enalapril stimulated mRNA concentration in both kidneys but renal renin did not rise in the hydronephrotic kidney. 5. Propranolol did not alter the response to sodium depletion in either kidney. 6. The macula densa is not crucial for the stimulation of renin synthesis following sodium depletion. However, it may regulate renin production after mRNA synthesis, possibly by controlling the conversion of prorenin to renin.

Animals↗
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↗
PubMed1977

Morphological effects of chronic tracheal ligation and drainage in the fetal lamb lung.

The relationship between lung liquid flow and fetal lung development has been studied at the cellular level using ultrastructural techniques. Continuous in utero tracheal ligation and drainage (over a period of 21-28 days) both result in malformations of the developing fetal lamb lung. Ligated lungs are larger, and drained lungs are smaller, than normal lungs at a similar gestational age. These changes are not merely due to altered lung liquid volume, but actual tissue growth thas been affected. Future alveolar wall thinning is enhanced in ligated lungs and inhibited in drained lungs, whilst the presence of differentiated alveolar type II cells (probably related to surfactant production) is decreased in ligated lungs and markedly enhanced in drained lungs. These results indicate the importance of fetal lung liquid in the regulation of pulmonary development in the fetus.

Animals↗