Underfill and overflow revisited: mechanisms of nephrotic edema.
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Animals↗
Biomedical subjects
D G Gardner
Publications and source records attributed to D G Gardner.
Coronal cemental hyperplasia in a cow.
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Animals↗
An orderly approach to the study of odontogenic tumours in animals.
In this paper odontogenic tumours in animals are discussed with the aim of developing a sound basis for further work in this relatively poorly understood field. The following recommendations are made: (1) Odontogenic tumours should be classified according to whether they are of epithelial, mesenchymal or of mixed epithelial and mesenchymal origin, rather than based on inductive changes. (2) The clinical behaviour implied by ameloblastoma, ameloblastic fibroma and odontoma should be carefully considered before these terms are incorporated into the diagnosis of any odontogenic tumour. (3) Caution should be exercised in designating specific odontogenic tumours in animals as being the counterpart of human tumours until their histopathological features and clinical behaviour have been proved to be equivalent. (4) Only tumours that exhibit the typical features of the basal cell layer of ameloblastomas should be designated as ameloblastomas. (5) Ameloblastic epithelium should not be used when odontogenic epithelium is intended. (6) These recommendations should be substantiated by reviewing odontogenic tumours in animals, although doing so will be difficult because of their rarity.
Ameloblastoma↗
Odontogenic cysts of the anterior mandible of sheep.
Cysts of this site are quite common in mature ewes in New Zealand and the British Isles, although their true prevalence is not yet known. In most examples, an unerupted incisor is embedded in their wall but some do not contain a tooth. The cysts are lined by parakeratinized stratified squamous epithelium and generally exhibit a flat interface between the epithelium and the connective tissue. They may become secondarily infected, in which case they exhibit chronic inflammation. In some cases, foci of cementum are attached to the epithelial lining. When a tooth is involved, the cysts arise from various locations along its crown, which in sheep is normally covered by a thin layer of cementum. Some of these unerupted teeth exhibit irregular hypercementosis and/or external resorption which is repaired by cementum. In some examples there is a fistula between the cyst and the oral cavity, either through a deep periodontal pocket or from the incisal edge of the unerupted tooth piercing the overlying mucosa.
Animals↗
Experimentally induced ameloblastomas: a critical review.
This article reviews the experimental induction of ameloblastomas with emphasis on the acceptability of the induced tumors as being truly equivalent to ameloblastomas in humans. Attempts to induce odontogenic tumors in experimental animals have been made sporadically since the early 1960's but the yield of ameloblastomas has been low. Tumors resembling ameloblastomas, but not completely typical histologically and apparently lacking the invasive qualities of ameloblastoma, have been produced in mice using polyoma virus. However, the most typical ameloblastomas have been those induced in opossums, using ethylnitrosourea. Consequently, it is recommended that this model be used in any further attempts to produce ameloblastomas experimentally.
Ameloblastoma↗
Divergent regulation of the human atrial natriuretic peptide gene by c-jun and c-fos.
Employing transient transfection analysis in neonatal rat cardiocytes, we have demonstrated that overexpression of c-jun results in a dose-dependent induction of the human atrial natriuretic peptide (hANP) gene promoter. Studies using a series of mutations in the hANP gene promoter identified a TRE-like, cis-acting regulatory sequence which conferred c-jun sensitivity. This same region was shown to interact with the c-jun/c-fos complex in an in vitro gel mobility shift assay. Selective mutation of this site suppressed basal activity of the hANP promoter and significantly reduced c-jun-dependent activation. Overexpression of c-fos had a biphasic effect on hANP gene promoter activity. At low levels, in concert with c-jun, it activated, while at higher levels it suppressed, transcription from the hANP gene promoter. This inhibition was both cell and promoter specific. hANP gene promoter sequences which mediate c-fos-dependent inhibition appear to be separable from those responsible for the induction. In addition, the protein domains on c-fos responsible for transcriptional activation and repression can be segregated topographically, with the inhibitory activity being localized to the carboxy-terminal domain. Thus, c-fos can activate or repress hANP gene expression through two separate functional domains that act on distinct regulatory elements in the hANP gene promoter. These data imply that the ANP gene may be a physiological target for c-fos- and c-jun-dependent activity in the heart and suggest a potential mechanism linking environmental stimuli to its expression.
Animals↗
Atrial natriuretic peptide synthesis in atrial tumors of transgenic mice.
Transgenic mice harboring a chimeric gene linking mouse protamine 1 5'-flanking sequence to the coding sequence of the simian virus 40 T-antigen develop spontaneous rhabdomyosarcomas of the right atria. The presence of the tumors is accompanied by dramatic elevations in plasma atrial natriuretic peptide (ANP) immunoreactivity (1,698 +/- 993 vs. 60 +/- 18 fmol/ml for controls) and hematocrit (56 +/- 8 vs. 51 +/- 2 for controls). The immunoreactive ANP (irANP) present in the tumors is similar in size to irANP found in normal mouse atria. ANP mRNA transcripts present in the tumors also appear to be very similar in overall size and 5'-termini to those produced in normal cardiac tissue. Microscopically, the tumors are composed of a disorganized array of densely packed abnormal-appearing cells. Immunocytochemistry and in situ hybridization analysis reveal considerable heterogeneity in ANP gene expression. ANP peptide and mRNA are detectable throughout the parenchyma of the tumors, but absolute levels of expression vary widely among different cells in the population. These tumors represent a potentially valuable model for the study of inappropriate ANP secretion and may provide a tissue source for the development of an ANP-producing atrial cell line.
Amino Acid Sequence↗
Stretch-dependent regulation of atrial peptide synthesis and secretion in cultured atrial cardiocytes.
We have developed a novel system to study stretch-dependent secretion of atrial natriuretic peptide (ANP) using cultured neonatal rat atriocytes in vitro. Application of tension (i.e., 2 sequential stretches) to cells grown on a flexible culture surface effected a dose-dependent increase in immunoreactive (ir) ANP release into the medium. Analysis of atriocyte cytoplasmic RNA 24 h poststretch revealed an increase in ANP mRNA levels of about ninefold relative to the unstretched controls. Medium ATP levels, measured as an index of cellular damage, were similar in control and stretched cells. Furthermore, cooling the cultures to 0 degrees C suppressed both basal as well as stretch-stimulated release. These findings argue against cellular damage and nonspecific release of irANP as an explanation for the increase in medium immunoreactivity. Stretch was incapable of amplifying the secretory response to prostaglandin F2 alpha, suggesting possible overlap in the pathways whereby these stimuli effect release of the peptide. The calcium channel blocker verapamil had no effect on stretch-dependent irANP release, whereas calmidzolium, a calmodulin inhibitor, suppressed basal as well as stretch-dependent secretion, implying a potentially important relationship between intracellular calcium metabolism and irANP release.
1-Methyl-3-isobutylxanthine↗
Cellular basis for blunted volume expansion natriuresis in experimental nephrotic syndrome.
Experimental nephrotic syndrome results in sodium retention, reflecting, at least in part, an intrinsic defect in renal sodium handling in the distal nephron. We studied the relationships among plasma atrial natriuretic peptide (ANP) concentration, sodium excretion (UNaV), and urinary cyclic GMP excretion (UcGMPV) in vivo, and the responsiveness of isolated glomeruli and inner medullary collecting duct (IMCD) cells to ANP in vitro, in rats with adriamycin nephrosis (6-7 mg/kg body weight, intravenously). 3-5 wk after injection, rats were proteinuric and had a blunted natriuretic response to intravenous infusion of isotonic saline, 2% body weight given over 5 min. 30 min after onset of the infusion, plasma ANP concentrations were elevated in normals and were even higher in nephrotics. Despite this, nephrotic animals had a reduced rate of UcGMPV after the saline infusion, and accumulation of cGMP by isolated glomeruli and IMCD cells from nephrotic rats after incubation with ANP was significantly reduced compared to normals. This difference was not related to differences in binding of 125I-ANP to IMCD cells, but was abolished when cGMP accumulation was measured in the presence of 10(-3) M isobutylmethylxanthine or zaprinast (M&B 22,948), two different inhibitors of cyclic nucleotide phosphodiesterases (PDEs). Infusion of zaprinast (10 micrograms/min) into one renal artery of nephrotic rats normalized both the natriuretic response to volume expansion and the increase in UcGMPV from the infused, but not the contralateral, kidney. These results show that, in adriamycin nephrosis, blunted volume expansion natriuresis is associated with renal resistance to ANP, demonstrated both in vivo and in target tissues in vitro. The resistance does not appear related to a defect in binding of the peptide, but is blocked by PDE inhibitors, suggesting that enhanced cGMP-PDE activity may account for resistance to the natriuretic actions of ANP observed in vivo. This defect may represent the intrinsic sodium transport abnormality linked to sodium retention in nephrotic syndrome.
3',5'-Cyclic-GMP Phosphodiesterases↗
Fibromatous epulis in dogs and peripheral odontogenic fibroma in human beings: two equivalent lesions.
This article compares the clinical and histopathologic features of the peripheral odontogenic fibroma in human beings and the fibromatous epulis in dogs. They are apparently equivalent lesions. Both are odontogenic tumors of limited growth potential that do not recur if adequately excised; both occur in middle and late adulthood of the species concerned. The one difference is that the peripheral odontogenic fibroma is a rare condition, whereas the canine fibromatous epulis is common.
Animals↗
Contiguous enlarged dental follicles with histologic features resembling the WHO type of odontogenic fibroma.
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Dental Sac↗
A central odontogenic fibroma exhibiting pleomorphic fibroblasts and numerous calcifications.
A case of an odontogenic fibroma with unusual histopathological features is described. The tumour exhibited numerous, plump, stellate fibroblasts, similar to those found in the so-called giant cell fibroma. This finding has not been described previously in odontogenic fibromas. This case also exhibited an unusually large number of calcifications. Neither of these features should affect the biological behavior of this lesion.
Calcinosis↗
Ameloblastic fibro-odontomas in animals.
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Animals↗
Arachidonic acid metabolites regulate the secretion of atrial natriuretic peptide in cultured rat atrial cardiocytes.
Prostaglandins F2 alpha and E2 increase release of immunoreactive (irANP) in primary cultures of rat atrial cardiocytes. This effect is independent of cell density in the cultures and does not appear to operate through a cAMP-dependent mechanism. Studies that probed the PGF2 alpha effect with a number of different pharmacological antagonists suggest that it is tied to a calmodulin-dependent step. This latter effect does not appear to be related to increased calcium entry through voltage-gated channels in the plasma membrane nor to mobilization of ryanodine-sensitive intracellular calcium pools. Inhibitors of the lipoxygenase pathway, a second avenue of arachidonate metabolism, resulted in a decrease in irANP release from cultured atrial or ventricular cardiocytes. Leukotriene C4, a lipoxygenase product, had a modest effect to promote irANP release over a 24-h period. However, pretreatment of anesthetized rats with nordihydroguarietic acid, a lipoxygenase inhibitor, had no effect on stretch-dependent release of irANP from the heart in vivo. These findings suggest that the prostaglandins represent the more important group of arachidonate metabolites in regulating irANP release physiologically.
1-Methyl-3-isobutylxanthine↗
Endothelin increases the synthesis and secretion of atrial natriuretic peptide in neonatal rat cardiocytes.
Endothelin (ET) effected a dose-dependent increment in atrial natriuretic peptide (ANP) secretion and ANP mRNA accumulation in neonatal rat atrial and ventricular cardiocytes but had no effect on the processing of the ANP prohormone to the mature ANP product. The secretagogue effect was not limited by cell density. Both basal and ET-dependent secretory activity were abrogated by the calmodulin antagonist calmidazolium but were unaffected by meclophenamate or pertussis toxin. The magnitude of the ET-dependent increment in ANP secretion was amplified by culturing the cells in a dynamically pulsating (vs. static) environment, implying an interaction between mechanical and agonist-mediated secretory stimuli in this system. ET also promoted immunoreactive ANP release from primary cultures of fetal rat hypothalamic cultures, suggesting that this regulatory function may be generally employed in ANP gene-expressing cells. These findings demonstrate that ET has parallel effects on ANP synthesis and secretion and support a role for this peptide in the regulation of local and circulating levels of the natriuretic hormone.
Animals↗
Interactions between ANP and ANG II in regulating blood pressure and sympathetic outflow.
In anesthetized rats with sinoaortic denervation, intracerebroventricular (icv) injection of atrial natriuretic peptide (ANP) resulted in decreased mean arterial blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (depressor effects), whereas icv angiotensin II (ANG II) produced increases in these variables (pressor effects). The depressor effects of ANP were slower in onset and longer in duration than the pressor effects of ANG II. Intracerebroventricular injection of the ANG II-receptor blocker sarthran or the ANG II-synthesis inhibitor captopril resulted in a significant reduction in MAP; HR and RSNA were not affected. Both sarthran and captopril abolished the depressor responses to icv ANP. In contrast, injection of an anti-rat ANP antibody, which blocked the depressor effects of icv ANP, did not by itself modify MAP, HR, or RSNA, nor did the antibody affect the pressor responses to icv ANG II. These data suggest that, in this animal model, the depressor effects of icv ANP are mediated by the inhibition of brain ANG II-dependent neural activity. These results also demonstrate that, in this preparation, the endogenous ANG II system actively contributes to the maintenance of basal MAP, whereas the central ANP system, at least in regions accessible to the antirat ANP antibody, plays little role in this maintenance.
Angiotensin II↗
Modulation of endothelin effects on blood pressure and hematocrit by atrial natriuretic peptide.
Infusion of endothelin has been observed to increase hematocrit, and the peptide also stimulates release of atrial natriuretic peptide (ANP) both in vitro and in vivo. We studied the relation of these two actions of endothelin in anesthetized, bilaterally nephrectomized Sprague-Dawley rats. Infusion of endothelin (25 ng/kg/min) for 45 minutes produced a modest increase in blood pressure of 12% from a baseline of 99 +/- 5 mm Hg and an increase in hematocrit of 8.0 +/- 0.6%, reflecting a reduction in plasma volume of 13.1 +/- 0.9%. These changes each exceeded greatly those observed after 45 minutes of vehicle infusion. Plasma protein concentration, however, increased only by 4.2 +/- 0.6%, suggesting protein extravasation, which was confirmed by finding an endothelin-dependent increase in the accumulation of Evans blue dye in heart, skeletal muscle, and intestine, but not liver, lung, brain, or testis. Endothelin infusion increased plasma immunoreactive ANP concentration from 196 +/- 50 to 722 +/- 203 pg/ml (p less than 0.02), and a close correlation existed between the increase in plasma immunoreactive ANP and immunoreactive endothelin concentrations as a result of the infusion (r = 0.84, p less than 0.01). Pretreatment of rats with rabbit anti-rat ANP antiserum did not affect baseline variables but led to an exaggerated increase in blood pressure (25.3 +/- 2.9%, p less than 0.002 versus endothelin alone). No change in hematocrit occurred. Thus, the increase in plasma immunoreactive ANP concentration resulting from endothelin infusion mediates the increase in hematocrit through an increase in vascular permeability to whole plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗