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Biomedical subjects

D Alcorn

Publications and source records attributed to D Alcorn.

At least 91 records · Page 5Linked to original sources
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↗
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

Morphological and biochemical characterization of four clonal osteogenic sarcoma cell lines of rat origin.

The ultrastructural and biochemical properties of four clonal osteogenic sarcoma lines, UMR 104, 105, 106, and 108, have been compared with uncloned osteogenic sarcoma cells and normal osteoblast-rich cells derived from newborn rat calvaria. High alkaline phosphatase activity and activation of adenylate cyclase by parathyroid hormone were used as biochemical markers of osteoblastic cells. Cloning enriched both of these parameters above those of the parent tumor and far higher than that seen in normal cells, suggesting enrichment of the osteoblast phenotype. Both of these properties have been retained through many passages in culture. Morphologically, the clonal lines have also retained the "blast"-like appearance of the uncloned osteogenic sarcoma cells and consist mainly of flat, relatively featureless cells. Many cells with mitotic figures were observed, indicating continuous cell division taking place in the malignant cells. Each clonal line gave rise to characteristic tumors when reinjected into rats. It is concluded that the clonal osteogenic sarcoma lines are highly differentiated tumor lines which have conserved the differentiated properties of the mature osteoblast, making them a suitable model for the study of the effects of hormones on the growth of a differentiated tumor, as well as for the study of hormonal regulation of the osteoblast.

Acid Phosphatase↗
PubMed1982

Ultrastructural morphology of granule release from juxtaglomerular myoepithelioid and peripolar cells.

The morphology of granule release from juxtaglomerular myoepithelioid and peripolar cells has been examined. Renin release occurs from myoepithelioid granules by an unusual form of exocytosis via deep channel-like invaginations of the plasma membrane. Such release occurs towards the juxtaglomerular interstitium as well as towards the arteriolar lumen. Peripolar cell granule exocytosis occurs directly into the urinary space in sodium-depleted sheep, tentatively supporting the speculation that it may be the source of an intrarenal sodium-retaining hormone.

Animals↗
PubMed1981

Selective distal nephron damage during isolated kidney perfusion.

The morphologic characteristics of the isolated perfused rat kidney were examined by light and electron microscopy. Following perfusion for 90 min, the cortex appeared normal except for the development of spaces in glomerular mesangial regions and ultrastructural abnormalities in very few proximal tubular cells. In the medulla, descending limbs of the loops of Henle and Collecting tubules appeared normal. During perfusion, however, even under optimal conditions, consistent and reproducible changes rapidly developed in cells of the thick ascending limb of Henle's loop, more specifically, in cells of the straight portion of the distal tubule in the inner stripe of the outer medulla. The changes became progressively more severe as perfusion continued and ranged from swelling of mitochondria at 15 min to complete cellular disruption by 90 min. Horseradish peroxidase added to the perfusion medium was found in and between damaged cells and in the interstitial tissue adjacent to affected areas. The pathogenesis of these selective medullary distal tubular abnormalities may relate to the specialized functional activity of this segment of the nephron. Such abnormalities may contribute to the specific functional defects of the preparation.

Animals↗
PubMed1981

Functional properties of hormonally responsive cultured normal and malignant rat osteoblastic cells.

Certain metabolic properties of hormonally responsive osteogenic sarcoma cells derived from a transplantable rat tumor have been compared with those of related normal rat bone cells. All studies were carried out on cells grown in monolayer culture. Normal rat bone cells derived by repeated collagenase/trypsin digestion of newborn rat calvaria. Bone cells selected for comparison were thought to be osteoblast-like, as judged by enrichment of alkaline phosphatase and adenylate cyclase responsiveness to parathyroid hormone and prostaglandin E2. The adenylate cyclases of the two cell strains were similarly stimulated by a range of prostanoids and their metabolites and analogs. Morphology showed the two cell strains to be similar; the only obvious difference was a multilayering of cells in the sarcoma cultures, while the normal cultures showed abundant extracellular fibril formation which was not seen in the tumor cells. Investigation of the cAMP-dependent protein kinase isoenzymes showed the presence of two forms in both cell types, one eluting at a low salt concentration and the other at a high salt concentration. There was approximately twice the amount of the first isoenzyme compared to the second isoenzyme. The results indicate the usefulness of the two cell strains to elucidate further the molecular mechanisms of action of parathyroid hormone and prostaglandins.

Acid Phosphatase↗
PubMed1981

Distribution of anionic groups in the glomerular capillary wall in rat nephrotoxic nephritis and aminonucleoside nephrosis.

It is widely believed that polyanionic plasma proteins, such as albumin, are normally prevented from penetrating the glomerular capillary wall by the presence of intrinsic fixed negative charges in the wall. There is also strong support for the corollary that proteinuria occurs in glomerular disease as a result of loss of such charges. Morphologic studies using cationic 'stains' have indicated that anionic groups can be detected in normal glomeruli and that, in proteinuric states, there is an apparent reduction in such staining. Because most of the latter claims are based largely upon light microscopic studies, critical reassessment at the electron microscopic level is necessary, particularly using the recently developed technique of in situ drip-fixation of superficial glomeruli during good blood flow. In normal rats, this technique results in heavy cationic colloidal iron staining of podocytic epithelial surfaces but little or no staining in the basement membrane or within endothelial fenestrae. In two experimental proteinuric models, rat nephrotoxic nephritis and aminonucleoside nephrosis, there was no loss of colloidal iron staining on podocytic epithelial surfaces at any stage. There was, however, a striking alteration in glomerular architecture in each model, particularly affecting podocytic epithelium. Thus, there was extensive replacement of foot processes by flattened expanses of epithelial cytoplasm, associated with scattered focal gaps in the epithelial covering of the basement membrane. It therefore appears that the reduction of glomerular polyanion seen by light microscopy in glomerular disease results simply from a decrease in visceral epithelial surface area rather than a loss of intrinsic polyanion from the filtering portion of the glomerular capillary wall.

Animals↗
PubMed1980

Morphological effects of chronic bilateral phrenectomy or vagotomy in the fetal lamb lung.

The relationship between fetal espiratory activity and fetal lung development has been studied at the cellular level using two experimental models. Chronic bilateral phrenectomy over a period of 20-28 days during the last trimester of the fetal lamb resulted in hypoplastic lungs, although cellular maturity, as indicated by the presence of alveolar epithelial Type II cells, was present. In the lungs from fetal lambs undergoing sham operations for a similar time course there was evidence of enhanced alveolar proliferation when compared with lungs from normal fetal sheep of a similar gastational age, most probably as a result of operative stress. Following chronic bilateral vagotomy no changes in size or histology of the fetal lamb lungs were detected. At an ultrastructural level, however, inclusions of Type II cells consistently showed the loss of the typical osmiophilic lamellated appearance. These results indicate the importance of the fetal breathing apparatus in maintaining a volume of lung liquid which is adequate for normal pulmonary development, particularly during the phase in which alveoli are formed.

Animals↗
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↗
PubMedDate not supplied

Actions of endothelin-1 on cultured rat renomedullary interstitial cells are modulated by nitric oxide.

1. Cultured renomedullary interstitial cells (RMIC) isolated from 4-week-old Sprague-Dawley rat kidneys possess ETA receptors, as identified by reverse transcription-polymerase chain reaction (RT-PCR). 2. Treatment with endothelin (ET)-1 (10(-6) mol/L) increases the intracellular inositol 1,4,5-trisphosphate concentrations within 10 s and intracellular calcium concentrations after 7 s. 3. Endothelin-1 (10(-7) and 10(-10) mol/L) induced increases in intracellular cAMP concentrations, but only in the presence of N omega-nitro-L-arginine, a nitric oxide synthase (NOS) inhibitor. Addition of ET-1 (10(-10) mol/L) to the RMIC culture led to increases in intracellular cGMP concentrations through activation of NOS. 4. In the presence of ET-1 (10(-7) and 10(-10) mol/L) and during NOS inhibition, RMIC responded with increased cell proliferation and extracellular matrix (ECM) synthesis. These responses were abolished by BQ-123 (10(-6) mol/L), suggesting mediation via the ETA receptor subtype. The proliferative effect of ET-1 was also abolished by atrial natriuretic peptide (10(-6) mol/L). 5. The present study provides evidence that binding of ET-1 to ETA receptors on RMIC activates several intracellular second messenger systems that mediate cell proliferation and ECM synthesis. 6. These results also highlight an important interaction between ET-1 and nitric oxide in the control of RMIC function.

Adrenal Medulla↗
PubMedDate not supplied

Cellular localization of endothelin receptor subtypes in the rat kidney following in vitro labelling.

1. We have previously shown that [125I]-endothelin (ET) receptor binding is localized almost exclusively to the fenestrated endothelial cells of glomerular capillaries and peritubular capillaries in the rat kidney following systemic administration of the radioligand in vivo. Because of the lack of specific ET receptor binding in other glomerular and tubular structures following in vivo labelling, we undertook further studies, using electron microscopic autoradiography and ET receptor subtype selective ligands, to investigate whether other renal components also contain ET receptor binding and, if so, to determine the cellular localization of the ET receptor subtypes, ETA and ETB, following in vitro labelling. 2. At the electron microscopic level, ET binding sites were localized primarily to the fenestrated endothelium of glomerular and peritubular capillaries of the cortex, inner stripe of the outer medulla and the inner medulla. ET binding sites also occurred overlying renomedullary interstitial cells (RMIC) of the inner medulla. 3. The ETB receptor selective agonist, sarafotoxin 6c (S6c), abolished ET binding in the vascular endothelium throughout the kidney, while the ETA receptor selective antagonist, BQ123, was without effect. Both BQ123 and S6c partially inhibited the binding in the RMIC of the inner medulla. 4. These results indicate that ET receptor binding in the fenestrated endothelium in the glomerular capillaries and peritubular capillaries belongs mainly to the ETB subtype, whereas both ETA and ETB subtypes are present in the RMIC.

Animals↗
PubMedDate not supplied

Angiotensin converting enzyme inhibition in the postnatal rat results in decreased cell proliferation in the renal outer medulla.

1. Chronic angiotensin converting enzyme (ACE) inhibition or AT1 antagonism during postnatal development in the rat has been shown to cause renal tubular and vascular damage, particularly in the outer medulla. 2. The effects of ACE inhibition were investigated at a stage of development before the renal outer medulla is fully established. 3. Sprague-Dawley rat pups were given daily i.p. injections of either enalapril or saline from days 3-10. At day 11, kidneys were perfusion-fixed for either electron microscopy or immunocytochemistry. Sections were incubated in proliferating cell nuclear antigen (PCNA) antisera and the avidin-biotin immunoperoxidase method was used to detect an immunoreactive product, indicative of proliferating cells. 4. Following enalapril treatment, the normal structural arrangement of the outer medulla was disrupted compared with controls. Cell proliferation (PCNA-positive cells) in the medullary rays was reduced in enalapril-treated kidneys compared with control kidneys. 5. Thus, angiotensin II appears to be essential for normal tubular and vascular growth in postnatal renal development in the rat.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Angiotensin II antagonism and pre-glomerular arterial wall dimensions in the kidney of the spontaneously hypertensive rat.

The effects of the angiotensin II type 1 receptor antagonist TCV-116 on the wall dimensions of the interlobular and arcuate arteries have been studied. SHR rats were treated with TCV-116 between 4 and 10 weeks, at which time their kidneys were perfusion-fixed and examined using stereological techniques. TCV-116 reduced arterial pressure and left ventricle/body weight ratio, but did not reduce renal arterial wall dimensions. For both arcuate and interlobular arteries, wall density/kidney ratio was significantly greater in the TCV-116 treated SHR than in untreated SHR and wall:lumen ratio was also significantly greater for the interlobular arteries in the TCV-116 treated rats. These findings are similar to those obtained previously using enalapril, and indicate that hypertrophy of the walls of these intra-renal arteries is not secondary to the elevated arterial pressure, unlike in other vascular beds.

Angiotensin II↗