Churg-Strauss syndrome in a child: retina and optic nerve findings.
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Child↗
Biomedical subjects
D Alcorn
Publications and source records attributed to D Alcorn.
Renomedullary interstitial cells in culture; the osmolality and oxygen tension influence the extracellular amounts of hyaluronan and cellular expression of CD44.
Our previous studies have suggested a role for renomedullary interstitial cells (RMICs) and renal medullary hyaluronan (HA) in water homeostasis. In the present study, cultured rat RMICs were used to examine the relationship of osmolality and oxygen tension on the extracellular amount of HA in the culture and to the cellular immunoreactivity to CD44, a HA binding protein. Under isotonic (330 mOsm(.)kg(-1) H(2)O), normoxic (20% O(2)) conditions, supernatant from sub-confluent RMICs contained 120+/-37 pg 10(4) cells(-1) 24 h(-1) of HA. Under hyperosmotic conditions (630 mOsm kg(-1) H(2)O), HA in the supernatant was decreased by 42% and under hypoosmotic conditions (230 mOsm kg(-1) H(2)O) it was doubled. Under hypoxic, iso-osmolar conditions (5% and 1% O(2), 330 mOsm kg(-1) H(2)O) this HA content was decreased by 56 and 48%, respectively, compared with normoxic, iso-osmolal conditions. Expression of CD44 on sub-confluent cells increased with increasing osmolality, as shown by immunostaining and flow cytometric analysis. The increases in CD44 from 330 to 630, 930 and 1230 mOsm kg(-1) H(2)O amounted to 5, 142 and 212%, respectively. Low oxygen tension (5% O(2)) decreased the intensity of CD44 immunofluorescence by 31%. Cell viability was similar at all conditions studied. In summary, these data indicate that cultured RMICs produce HA and are immunoreactive to CD44. In the supernatant of RMICs, the HA content decreases under hyperosmotic, hypoxic conditions. Conversely, CD44 immunoreactivity increases under hyperosmotic conditions. These results may explain our previous in vivo findings of a decreased renal papillary HA content during anti-diuresis and an increased content during water diuresis. The results support the concept that RMICs play an important role in renal water handling.
Animals↗
Chronic angiotensin converting enzyme inhibition enhances renal vascular responsiveness to acetylcholine in anaesthetized rabbits.
OBJECTIVE: To determine whether 6 weeks continuous treatment with an angiotensin converting enzyme (ACE) inhibitor reduced renal vascular responsiveness in vivo, since this treatment results in extensive phenotypic conversion of afferent arteriolar cells from contractile to endocrine-like, renin secretory cells. METHODS: Enalapril (10 microg/kg per h s.c.) was delivered continuously for 6 weeks. In anaesthetized rabbits (treated or sham), arterial blood pressure and renal blood flow were measured and renal responsiveness tested by constructing dose-response curves to bolus doses of phenylephrine, angiotensin II and acetylcholine delivered directly into the renal artery. RESULTS: ACE inhibition resulted in a significant shift to the left in the renal vascular conductance responses to acetylcholine (P < 0.005) and angiotensin II (P < 0.05), indicating enhanced, not reduced, responsiveness to these agents. There were no significant effects of chronic ACE inhibition on the conductance responses to phenylephrine. CONCLUSIONS: Contrary to our hypothesis, 6 weeks ACE inhibition did not reduce renal vascular responsiveness to three vasoactive agents, suggesting that the phenotypic changes observed in the afferent arterioles and to a lesser extent the interlobular arteries, were either insignificant or compensated for by other changes in renal circulatory control.
Acetylcholine↗
Renal vascular resistance properties and glomerular protection in early established SHR hypertension.
OBJECTIVE: To characterize the in vivo vascular properties of the spontaneously hypertensive rat (SHR) renal vascular bed by examining vascular conductance/resistance responsiveness to vasoactive agents in vivo and determining whether the filtration surface area of glomerular capillaries is reduced. DESIGN AND METHODS: in vivo renal blood flow responses to intrarenally administered angiotensin II, phenylephrine and acetylcholine were compared in 10-week-old SHR and Wistar-Kyoto (WKY) rats using a wide range of doses from near threshold to near maximal effect. Unbiased stereological techniques and high-resolution light microscopy were used to estimate the surface area and length of glomerular capillaries, and evidence of capillary damage. RESULTS: The SHR renal bed demonstrated significantly enhanced dose-vascular resistance responses to vasoconstrictors. For vascular conductance and calculated radius of resistance vessels, the SHR curves were significantly lower across the full dilator-constrictor range examined, but the dose-related changes were similar to those of WKY rats. There were only modest enhancements of the renal blood flow responses in the SHR, evident only when renal blood flow was reduced by more than 50% SHR and WKY rats did not differ in mean glomerular capillary surface area (0.13+/-0.02 mm2 and 0.14+/-0.02 mm2, respectively) or length (5.76+/-0.85 mm and 5.48+/-0.90 mm, respectively) nor was there evidence of glomerular capillary damage in either strain. CONCLUSIONS: The renal vascular bed of the SHR in vivo exhibits reduced vascular conductance across a wide vasomotor range, compatible with findings in other vascular beds. We have further shown no evidence of reduced glomerular capillary surface area or damage. These findings are compatible with the hypothesis that the reduced conductance of the SHR pre-glomerular vasculature increases the aorta-capillary pressure gradient thus protecting the glomerular capillaries from systemic hypertension at this age.
Animals↗
Diffuse unilateral hemorrhagic retinopathy associated with accidental perinatal strangulation. A clinicopathologic report.
OBJECTIVE: To report an unusual case of diffuse retinal hemorrhage associated with strangulation in a neonate with a tightly wrapped nuchal cord around his neck at birth who was noted to have eyelid and subconjunctival petechial hemorrhages upon delivery. METHODS: Clinical diagnostic examination as well as postmortem gross and histopathologic examination of ocular and central nervous system structures was performed. RESULTS: Funduscopic and gross pathologic examination of the eyes revealed extensive unilateral retinal hemorrhage of the right eye only. This was corroborated by histopathologic studies, which revealed unilateral diffuse hemorrhage throughout all nuclear layers of the retina with a particularly dense nerve fiber layer and sub-internal limiting membrane hemorrhage in the macula along with extraocular muscle and episcleral hemorrhage. Clinical, gross, and microscopic examination also revealed multiple areas of hemorrhage involving the right side of the brain and throughout the cerebellum. CONCLUSION: Although retinal findings in nonaccidental trauma are common, accidental strangulation retinopathy in neonates is a rare occurrence. To the authors' knowledge, this case is the only documented histopathologic study of hemorrhagic retinopathy associated with strangulation in the literature.
Airway Obstruction↗
Congenital circumscribed choroidal haemangioma associated with infantile hepatic haemangioendotheliomatosis.
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Choroid Neoplasms↗
Imaging of renal medullary interstitial cells in situ by confocal fluorescence microscopy.
Renal medullary interstitial cells are a prevalent and characteristic feature of the inner medulla of the kidney, but the physiological significance of this is unclear. We have developed a method for imaging renal medullary interstitial cells in situ by loading the cells with fluorescent dyes and monitoring their distribution using confocal microscopy. The pH-sensitive probe 2'7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester was used as a marker of cytoplasmic volume and therefore of cell morphology. Nile Red was used to demonstrate the presence of renal medullary interstitial cell lipid droplets. Papillae were excised from 100 g Sprague-Dawley rats and loaded with the appropriate dye. The papillae were then examined using a Leica TCS 4D confocal microscope and oil immersion lenses. Fluorescence was excited (488 nm) using an argon laser and emission wavelengths above 515 nm collected using a long pass filter. Images of papillae loaded with 2'7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester clearly demonstrate a ladder-like arrangement of renal medullary interstitial cells. More detailed examination revealed the presence of cytoplasmic extensions that appear to make close contact with adjacent loops of Henle. Three-dimensional reconstructions of serial sections revealed spiral arrangements in some ladders of renal medullary interstitial cells. Nile Red-labelled lipid droplets of 0.5-1.0 microm diameter were located throughout the cytoplasm of renal medullary interstitial cells and especially within the cytoplasmic extensions. These experiments highlight the ability of confocal microscopy to allow investigation of renal medullary interstitial cells in situ.
Animals↗
Development of the renal interstitium.
The kidney is derived from two tissue sources and develops through a series of mesenchymal-epithelial transitions and epithelial-mesenchymal interactions to form an epithelial tubular organ embedded in an interstitium derived from mesenchyme. The primary interstitium of the embryonic kidney undergoes significant differentiation to form the adult counterpart whose diverse cells have structural and functional characteristics that relate to their local milieu. Whether the adult interstitial cells retain the capacity to transform to other cell types and thus play a role in pathophysiological conditions appears more and more likely as the plasticity of cells becomes apparent. Besides forming the adult interstitium, the primary interstitium is active in metanephric development, with specific roles in nephron growth and collecting duct growth and arborization. Interruptions to the development of the interstitium or amelioration of its developmental capacity result in severely disrupted kidneys. The development of the renal interstitium is an essential component in the process of renal genesis.
Animals↗
Renomedullary interstitial cells regulate hyaluronan turnover depending on growth media osmolality suggesting a role in renal water handling.
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Animals↗
Rat renomedullary interstitial cells possess bradykinin B2 receptors in vivo and in vitro.
1. Renomedullary interstitial cells (RMIC), abundant throughout the medulla of the kidney, have been demonstrated to have binding sites for many vasoactive peptides, including atrial natriuretic peptide, endothelin, angiotensin II and bradykinin (BK). These observations would support the hypothesis that interactions between RMIC and vasoactive peptides are important in the regulation of renal function. 2. We aimed to localize the BK B2 receptor binding site to RMIC in vivo and to also demonstrate that these receptors are biologically active in vitro. 3. The present study demonstrates BK B2 binding sites on RMIC of the inner stripe of the outer medulla and the inner medulla of the rat kidney in vivo. 4. We further demonstrate that the BK B2 radioligand [125I]-HPP-Hoe140 specifically bound to rat RMIC in vitro. In addition, reverse transcription-polymerase chain reaction detected the mRNA for the BK B2 receptor subtype in cell extracts. 5. For RMIC in vitro, cAMP levels were increased at 1 min and cGMP levels were increased at 2 min after treatment with 10(-10) and 10(-7) mol/L BK, respectively. Inositol 1,4,5-trisphosphate was increased at 10 s treatment with both 10(-6) and 10(-7) mol/L BK. 6. For RMIC in vitro, BK induced an increase in cell proliferation ([3H]-thymidine incorporation) and an increase in extracellular matrix synthesis (ECM; trans-[35S] incorporation), both effects mediated by BK B2 receptors. 7. We conclude that BK B2 receptors are present on RMIC both in vivo and in vitro. These receptors are coupled to intracellular second messenger systems and, in vitro, their stimulation results in cellular proliferation and synthesis of ECM.
Animals↗
Absorption of hyaluronan applied to the surface of intact skin.
Hyaluronan has recently been introduced as a vehicle for topical application of drugs to the skin. We sought to determine whether hyaluronan acts solely as a hydrophilic reservoir on the surface of intact skin or might partly penetrate it. Drug-free hyaluronan gels were applied to the intact skin of hairless mice and human forearm in situ, with and without [3H] hyaluronan. [3H]hyaluronan was shown by autoradiography to disseminate through all layers of intact skin in mouse and human, reaching the dermis within 30 min of application in mice. Cellular uptake of [3H]hyaluronan was observed in the deeper layers of epidermis, dermis, and in lymphatic endothelium. Absorption through skin was confirmed in mice by chromatographic analysis of blood, urine, and extracts from skin and liver, which identified 3H as intact hyaluronan and its metabolites, free acetate and water. Hyaluronan absorption was similarly demonstrated without polyethylene glycol, which is usually included in the topical formulation. [3H]hyaluronan absorption was not restricted to its smaller polymers as demonstrated by the recovery of polymers of (360-400 kDa) from both blood and skin. This finding suggests that its passage through epidermis does not rely on passive diffusion but may be facilitated by active transport. This study establishes that hyaluronan is absorbed from the surface of the skin and passes rapidly through epidermis, which may allow associated drugs to be carried in relatively high concentration at least as far as the deeper layers of the dermis.
Administration, Topical↗
Ovine AQP1: cDNA cloning, ontogeny, and control of renal gene expression.
The cDNA for the ovine aquaporin 1 (AQP1) was obtained and found to be 97%, 88%, and 85%, respectively, homologous to the bovine, human, and rat AQP1 cDNA. The level of total kidney mRNA expressed as a ratio to glyceraldehyde-3-phosphate dehydrogenase increased sevenfold from 60 days to 140 days of gestation (term=150 days) and reached adult values by 6 weeks after birth. Treatment of pregnant ewes (and their fetuses) at 64 and 74 days of gestation with dexamethasone (0.76 mg/h for 48 h) resulted in a small but statistically significant increase in AQP1 mRNA only in the 74-day fetuses. By immunohistochemistry, it was shown that the increase in AQP1 mRNA with dexamethasone resulted largely from an increase in maturity of the inner zone of the fetal renal cortex (i.e., more tubules) as well as stronger expression of AQP1 in proximal tubules and thin descending limbs of loops of Henle. A similar effect occurred in fetuses infused for 3 days with angiotensin I (6.7 microg/h) in the last third of gestation.
Adult↗
Angiotensin II inhibits growth of cultured embryonic renomedullary interstitial cells through the AT2 receptor.
The high abundance of angiotensin II (Ang II) AT2, relative to the AT1 receptor subtype in developing kidneys may be related to their potential as mediators of cell growth, although little evidence exists to support this concept. Renomedullary interstitial cells (RMICs) differentiate early in embryonic kidneys and are important in subsequent nephron development. These cells have been shown in vivo to possess AT2 binding sites, although the functional significance of these sites remains unknown. The aim of the current investigation was to examine the actions of Ang II on cultured embryonic renomedullary interstitial cells (ERMICs). 125I-[Sar1, Ile8]Ang II specifically bound to AT1 and AT2 receptors on ERMICs, and their mRNAs were detected by reverse transcription--polymerase chain reaction (RT-PCR). Angiotensin II (10(-6) M) increased intracellular IP3 concentrations at 20 seconds, and decreased intracellular cAMP concentrations after 10 minutes. Angiotensin II (10(-6) M) induced an increase in [3H]thymidine incorporation, mediated through the AT1 receptor subtype. Basic fibroblast growth factor (bFGF; 20 ng/ml) also increased 3[H]thymidine incorporation after 24 hours of treatment, an effect that was attenuated by subsequent addition of Ang II (10(-6) M). This antiproliferative action of Ang II was blocked by PD 123319 (10(-6) M), an AT2 receptor antagonist, and was not affected by losartan (10(-6) M), an AT1 receptor antagonist. These results indicate a dual role for Ang II in regulating ERMIC mitogenesis: a growth stimulating effect mediated by the AT1 receptor subtype, and an antiproliferative effect mediated by the AT2 receptor subtype.
Angiotensin II↗
Localization and interactions of vasoactive peptide receptors in renomedullary interstitial cells of the kidney.
Vasoactive peptides regulate renal medullary microcirculation and tubular function, but the localization of their receptors and mechanisms of actions are currently unknown. Using electron microscopic autoradiography, we have mapped the receptors for angiotensin II (Ang II [AT1 and AT2]), endothelin (ET(A) and ET(B)), and bradykinin (B2) in the rat renal medulla. Although these peptide receptors show distinct vascular and tubular distributions, they overlap strikingly in renomedullary interstitial cells (RMICs) of the inner stripe and the papilla. Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern analysis, mRNAs for AT1A, ET(A), and B2 receptors were detected in cultured adult RMICs. Ang II increases intracellular inositol 1,4,5-triphosphate (IP3) and [Ca2+]i and stimulates [3H]thymidine incorporation and extracellular matrix (ECM) synthesis via AT1A receptors. Endothelin and bradykinin also stimulate cell proliferation and ECM synthesis in RMICs through ET(A) and B2 receptors, respectively, but the actions of endothelin are modulated by concurrent nitric oxide production. By contrast, AT2 receptor mRNA was detected only in embryonic RMICs, in which Ang II inhibits cell proliferation through this receptor. These results suggest that multiple vasoactive peptides may interact with RMICs to exert endocrine and/or paracrine influences on renal medullary microcirculation and tubular function.
Animals↗
The renin-angiotensin system and the development of the kidney and adrenal in sheep.
1. The earliest form of the kidney, the pronephros, does not really occur in the ovine embryo; instead, a giant glomerulus forms at the anterior end of the mesonephros. 2. In the sheep, the mesonephros is present from 11-38% of total gestation (150 days) and produces a dilute urine, as well as expressing the genes for erythropoietin, renin, angiotensinogen, angiotensin-converting enzyme and the angiotensin II (AngII) receptors AT1 and AT2. 3. The ovine metanephros begins to develop at 18% of gestation and nephrogenesis is complete several weeks before birth. All components of the renin-angiotensin system (RAS) are expressed from at least 27% of gestation. 4. Both AT1 and AT2 receptors are expressed by the adrenocortical cells early in gestation but, at mid-gestation, exogenous AngII does not stimulate aldosterone secretion in vivo. 5. Preliminary results suggest that AngII has important roles in renal development in the ovine foetus but the role(s), if any, in adrenal development, remains to be investigated.
Adrenal Glands↗
Ovine amniotic and allantoic epithelia across gestation.
BACKGROUND: Extensive studies on the regulation of the volume and composition of amniotic and allantoic fluid in the sheep have suggested that the amniotic and allantoic membranes must play an active role in these processes. Little is known of the functional morphology of the sheep amnion and allantois beyond the presence of an epithelium overlying connective tissue. METHODS: The ovine amnion and allantois were characterized at a range of gestational ages (27-140 days of gestation, where term is 145-150 days) by electron microscopy (SEM and TEM) and the presence of transporting ATPases examined by use of immunohistochemistry (Ca++-ATPase) and in situ hybridization (Na,K-ATPase). RESULTS: With increasing gestational age, the cell height of epithelium of the membranes increased, as did the number of apical microvilli and the length of zonulae occludentes. Epithelial cell cytoplasm increased in complexity, and cell shape changed from flattened to cuboidal. Proliferation of cells occurred until close to term. Immunoreactivity to Ca++-ATPase was present in the basolateral membranes at all stages of gestation examined, but hybridization with the alpha and beta subunits of Na,K-ATPase was present only at or after 100 days of gestation. CONCLUSIONS: The epithelia of the sheep amnion and allantois display characteristics typical of transporting epithelia. As the epithelia mature, changes related to increased capacity for solute and fluid transport regulation occur.
Allantois↗
Embryonic and postnatal development of the rat renal interstitium.
Whilst antihypertensive, structural and functional roles have been proposed for the cells of the renomedullary interstitium in the adult kidney, little is known about its role in renal development. Rat kidneys were studied throughout development, prenatally at gestational ages E14-E21 and postnatally at 0-28 days, by light microscopy, transmission and scanning electron microscopy and following immunocytochemistry. Renomedullary interstitial cells were observed as early as embryonic day E14, forming a loose, orderly network around branches of the ureteric bud. Paralleling the development of the first nephron structures, renomedullary interstitial cells were arranged in a concentric circular manner around collecting ducts. Following tubular and vascular growth from the cortex into the medulla, this arrangement resulted in the characteristic 'rungs of a ladder' appearance of interstitial cells between tubules, blood vessels and the collecting ducts. Renomedullary interstitial cells were closely adherent to basement membranes of tubules, blood vessels and collecting ducts from early in development. Contacts were absent between renomedullary interstitial cells and tubular structures in the process of remodelling, such as the hair-pin bends of the loops of Henle. At these foci laminin, a basement membrane glycoprotein was specificially localised to intracellular epithelial sites, whereas in more developed areas, laminin was restricted to epithelial basement membranes. Associated with the more mature structures, laminin was also localised to intracellular granules of renomedullary interstitial cells. Thus, renomedullary interstitial cells are present prior to and appear to be actively associated with tubule repositioning in the medulla, establishing themselves as integral to the process of renal development.
Age Factors↗
Ontogeny of angiotensin II receptors, types 1 and 2, in ovine mesonephros and metanephros.
By RNAse protection assay, hybridization histochemistry, and in vitro autoradiography it was shown that both mRNA and protein for AT1 and AT2 receptors were present in ovine fetal meso- and metanephroi at 40 days of gestation (term approximately 150 days). AT1 mRNA was localized to presumptive mesangial cells of glomeruli at 40-, 75-, 131-gestational-day-old fetuses and two-day-old lambs, in addition to being widely present in interstitial cells of the cortex and medulla, once these zones formed (60 days). By two days after birth the medullary AT1 distribution was confined to the inner stripe of the outer medulla. AT2 mRNA was present in peripheral interstitial/tissue of the mesonephros, and interstitial tissue surrounding developing glomeruli, but not the outermost nephrogenic mesenchyme in the metanephros from 40 to approximately 131 days (the period of active nephrogenesis). In addition, AT2 mRNA was localized to epithelial cells of the macula densa in metanephroi (40 to 131 gestational days) during, but not after completion, of nephrogenesis. These studies suggest that angiotensin II (Ang II) could have differentiating effects, via AT1 receptors, from very early in development. The unique epithelial site of AT2 expression in the macula densa raises the possibility that Ang II may play a role in the invariant positioning of the macula densa at the pole of its glomerulus, via this receptor.
Aging↗