Biomedical subjects
D G Gardner
Publications and source records attributed to D G Gardner.
Dentigerous cysts in animals.
This article is a review of the literature on dentigerous cysts in animals. Three different lesions have been referred to in the veterinary literature as dentigerous cysts. The first of these cysts, similar to those that occur in human beings, is extremely rare. The second lesion, an odontogenic cyst located in the anterior mandibles of mature sheep, is quite common in New Zealand and parts of Britain. The third is actually a teratoma that contains teeth and is found in the temporal region of young horses; it is also rare.
The relationship of the canine acanthomatous epulis to ameloblastoma.
This paper compares the microscopic features and clinical behaviour of the acanthomatous epulis in dogs with those of ameloblastoma in human beings. The acanthomatous epulis has similar microscopic features to one histological variant of human ameloblastoma, the acanthomatous ameloblastoma. Moreover, its clinical behaviour is equivalent to that of intraosseous ameloblastoma in human beings, not of the human peripheral (extraosseous) ameloblastoma, as has been suggested. The stroma of acanthomatous epulides varies and does not always resemble periodontal ligament, a feature that in dogs has been used to distinguish them from ameloblastomas. It is concluded that the acanthomatous epulis (1) is an ameloblastoma, (2) arises from the gingival epithelium in some cases, but (3) may also arise intraosseously and then break out of bone. We recommend the term canine acanthomatous ameloblastoma as being appropriate for this lesion.
The histopathological features of canine keratinizing ameloblastoma.
This paper describes the microscopical features of one variant of canine ameloblastoma. It is composed of islands and strands of odontogenic epithelium that have infiltrated through the surrounding stroma. Most of the basal cells are hyperchromatic, cuboidal and perpendicular to the basement membrane (palisading); in some areas their nuclei are located at the distal ends of the cells (reverse polarization) and their cytoplasm is vacuolated. These are the classical characteristics of the basal cell layer of ameloblastomas. The central cells of these tumours are closely-packed, spindle-shaped and exhibit cellular keratinization and calcification as prominent features. Amyloid is present between the neoplastic epithelial cells in some examples.
Regulation of the human atrial natriuretic peptide gene in atrial cardiocytes by the transcription factor AP-1.
The effects of overexpression of individual components of the AP-1 transcription complex (ie, c-fos and c-jun) were examined in neonatal rat atriocyte cultures. Cotransfection of a c-jun expression plasmid together with a test plasmid linking portions of the human atrial natriuretic peptide (hANP) gene promoter to a bacterial chloramphenicol acetyl transferase (CAT) reporter resulted in a dramatic increase in ANP gene promoter activity. This effect appeared to operate through a consensus TPA (phorbol 12-myristate 13-acetate) response element (ie, AP-1 binding site) located approximately 235 base pairs upstream from the start site of transcription. This same TPA response element appears to be responsible for induction of hANP gene promoter activity by the phorbol ester TPA. Cotransfection of the same hANP promoter-CAT reporter constructs with a c-fos expression vector resulted in an unpredicted inhibition of reporter gene expression. This inhibitory activity was localized to the carboxy terminus of the c-fos protein and dominated the more conventional AP-1-dependent activity located elsewhere in the c-fos molecule. These findings suggest potential mechanisms for linking regulatory signals operative at or near the cell surface to the control of transcriptional activity in the cell nucleus.
Designer natriuretic peptides.
Explore the source record for details and available documents.
Underfill and overflow revisited: mechanisms of nephrotic edema.
Explore the source record for details and available documents.
The glandular odontogenic cyst, a rare lesion that tends to recur.
This article reports an example of a rare, recently reported odontogenic cyst, the glandular odontogenic cyst. It is important because it can become quite large and tends to recur if treated by curettage or enucleation.
Coronal cemental hyperplasia in a cow.
Explore the source record for details and available documents.
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.
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.
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.
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.
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.
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.
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.
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.
Contiguous enlarged dental follicles with histologic features resembling the WHO type of odontogenic fibroma.
Explore the source record for details and available documents.