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D G Gardner

Publications and source records attributed to D G Gardner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ameloblastomas in cats: a critical evaluation of the literature and the addition of one example.

The English language literature on feline ameloblastomas was evaluated. Seven acceptable cases were found and one additional example is added in this article. These rare tumors have occurred in cats over the age of 6 years, affected both sexes, both jaws, and various breeds. Two microscopic variants have so far been reported, namely the follicular pattern and the keratinizing pattern, which is similar to the keratinizing ameloblastoma in dogs. Ameloblastomas in cats have been confused in the past with two other feline odontogenic tumors: the inductive fibro-ameloblastoma (feline inductive odontogenic tumor) and the "calcifying epithelial odontogenic tumor" (amyloid-producing odontogenic tumor).

Ameloblastoma↗
PubMed1998

Early captopril treatment prevents hypertrophydependent gene expression in hearts of SHR.

Treatment of spontaneously hypertensive rats (SHR) with captopril (100 mg . kg-1 . day-1) throughout development and during the first 16 wk of life leads to a reduction in blood pressure and left ventricular hypertrophy. Blood pressures and hypertrophy are reduced in these animals (vs. untreated SHR) for up to 24 wk after discontinuation of the drug. We used conventional blot hybridization and Western analysis to examine hypertrophy-dependent gene expression during this period. Ventricular expression of the atrial natriuretic peptide gene was reduced by >90% at 16 wk of age in the captopril-treated SHR. Expression increased in the 24 wk after discontinuation of treatment, but remained well below that of the untreated SHR. A similar reduction in ventricular c-myc gene expression was seen with captopril treatment. Neither renal expression of the atrial natriuretic peptide gene nor ventricular expression of the c-fos gene was affected by captopril. This study demonstrates that captopril treatment during a critical period of development in the SHR leads to a sustained reduction in hypertrophy-dependent myocardial gene expression, which does not revert to levels seen in the untreated SHR after discontinuation of the drug.

Animals↗
PubMed1998

Ligand-dependent regulation of NPR-A gene expression in inner medullary collecting duct cells.

Atrial natriuretic peptide (ANP) interacts with high-affinity, guanylyl cyclase-linked receptors in the inner medullary collecting duct (IMCD), where it exerts important regulatory control over sodium handling. We sought to determine whether receptor activity in these cells would be modulated (downregulated) by prolonged exposure to ligand. A number of natriuretic peptides (ANP, brain natriuretic peptide, and urodilatin) were found to decrease ligand-dependent natriuretic peptide receptor A (NPR-A) activity in IMCD cells. This inhibition was in direct proportion to their capacity to increase basal cGMP levels in this cell population. The reduction in receptor activity was accompanied by a dose- and time-dependent reduction in NPR-A mRNA levels in these cells. The decrease in transcript levels arose, in part, from a reduction in NPR-A gene transcription. ANP reduced NPR-A gene promoter activity in a transiently transfected IMCD cell population. 8-Bromo-cGMP was also effective in inhibiting NPR-A mRNA levels and NPR-A promoter activity, suggesting that the second messenger (i.e., cGMP) rather than ANP, itself, is responsible for downregulation of NPR-A gene expression.

Animals↗
PubMed1998

Suppression of ANP gene transcription by liganded vitamin D receptor: involvement of specific receptor domains.

We showed previously that liganded vitamin D receptor (VDR) effects a suppression of human atrial natriuretic peptide (hANP) gene-promoter activity in cultured neonatal rat atrial myocytes. In the present study, we have attempted to identify the structural domains of the VDR that are involved in mediating this suppression. We examined the effects of a series of VDR mutants on a cotransfected hANP promoter-driven chloramphenicol acetyltransferase (CAT) reporter. Neither the native VDR nor any of the mutants tested displayed inhibitory activity in the absence of the 1,25-dihydroxyvitamin D3 (VD3) ligand. Delta134, a deletant harboring solely the DNA binding region of the VDR, and L254G, a mutant shown to be defective in retinoid X receptor (RXR) heterodimer formation in other systems, were as effective as the native VDR in reducing promoter activity. HBD, a deletant containing only the hormone-binding domain of the VDR, and K246G, a point mutant that is defective in the activation function of the receptor, did not attenuate reporter activity. A similar activity profile was displayed when a positively regulated promoter containing a direct-repeat vitamin D responsive element (DR3-CAT) was examined in these cells. Liganded VDR, the delta134 mutant, and liganded L254G effected increases in DR3-CAT activity of 2.5-, 2-, and 4-fold, respectively. Two nonhypercalcemic analogues of VD3 (RO 23-7553 and RO 25-6760) displayed the same inhibitory activity as VD3. These studies suggest that the inhibition of hANP promoter activity requires both the DNA binding and activation functions of the receptor but does not appear to require formation of a classic RXR alpha-VDR heterodimer.

Analysis of Variance↗
PubMed1998

Transcription-modulating drugs: a new frontier in the treatment of essential hypertension.

While the promises of gene therapy may be years away from realization, the therapeutic use of drugs that act by modifying gene transcription is a well-established practice in clinical medicine. Although transcription-modulating drugs are frequently used in many different specialties, the deliberate development and use of these agents in cardiovascular medicine has been comparatively limited. However, research advances in the area of gene transcription and in the molecular genetic regulation of blood pressure, insulin resistance, lipid metabolism, and cell growth are providing new opportunities for controlling the expression of genes that are relevant to the pathogenesis of cardiovascular disease and essential hypertension. These research advances are beginning to converge in the development of transcription-modulating drugs with the potential to attack genetically determined risk factors that often cluster in patients with essential hypertension. Ligand-activated transcription factors that serve as receptors for small lipophilic compounds such as the thiazolidinediones and retinoids represent examples of potential therapeutic targets with direct effects on the expression of genes relevant to the pathogenesis of essential hypertension and its complications. Mounting evidence suggesting that the superior cardiorenal protective properties of converting enzyme inhibitors are related in part to their ability to indirectly modify the expression of genes in the heart and vasculature provides provisional support for the clinical value of this therapeutic approach. Given the success of transcription-modulating drugs in the treatment of type II diabetes and many other clinical disorders, it is anticipated that these agents will be developed as tools for the prevention and treatment of hypertension and cardiovascular disease in the not too distant future.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Mechanical strain increases expression of the brain natriuretic peptide gene in rat cardiac myocytes.

Using a device that applies cyclical strain (1 Hz) to ventricular cardiocytes cultured on collagen-coated silicone elastomer surfaces, we have demonstrated strain-dependent increases in brain natriuretic peptide (BNP) secretion, BNP mRNA levels, and expression of a transiently transfected -1595 human BNP-luciferase reporter. When actinomycin D (10 microM) was introduced concomitantly with the strain stimulus, the strain-induced increase in BNP mRNA was eliminated, and the decay of transcripts was identical in the control and strained cells, indicating the lack of independent effects on transcript stability. Strain-dependent -1595 human BNP-luciferase activity was completely inhibited by chelerythrine, 2-aminopurine, genistein, and W-7 and only partially or not at all by KN-62, wortmannin, and H-89. The effects of these individual agents paralleled their effects on mitogen-activated protein kinase (MAPK) activity, but not c-Jun N-terminal kinase (JNK) activity, in the cells. Overexpression of wild-type MAPK and, to a lesser extent, JNK increased strain-dependent BNP promoter activity, whereas dominant-negative mutants of MAPK kinase, JNK kinase, or Ras completely blocked strain-dependent reporter activity. These findings provide the first demonstration that mechanical strain can increase myocardial gene expression through a transcriptional mechanism and suggest important roles for MAPK and JNK in mediating this effect.

Animals↗
PubMed1997

Residual cysts.

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Chronic Disease↗
PubMed1997

The relationship of adamantinomatous craniopharyngioma to ghost cell ameloblastoma of the jaws: a histopathologic and immunohistochemical study.

The objective of this investigation was to study the relationship of the ghost cell ameloblastoma (GCA), which is a form of type II calcifying odontogenic cyst (COC), to the adamantinomatous craniopharyngioma (ACP). H&E sections of 26 examples of ACP were compared to three cases of GCA and to the reported microscopic features of that tumor. Clinical records of the ACPs were studied to determine their biologic behavior compared to that of the ameloblastomas. Immunohistochemical studies of nine examples of ACP were performed for KL1 (high mol.wt cytokeratins), 5D3 (low mol.wt cytokeratins) and involucrin (characteristic of terminally differentiated keratinocytes) using the peroxidase-antiperoxidase method. The results were compared with those reported for COC and ameloblastoma. ACP and GCA exhibited similar microscopic features, including pre-ameloblasts, tissue resembling stellate reticulum, ghost cells and calcifications; both tumors grew slowly and were invasive. ACP and COC, and by interpolation GCA, exhibited similar features with all three antibodies. The ghost cells did not exhibit any immunoreactivity but the adjacent cells stained positively for involucrin. The immunological features of ACP were similar to those reported in ameloblastomas for squamous differentiation. However, because of their rarity, no ameloblastomas exhibiting keratinization, including ghost cells, have yet been studied with these antibodies. We conclude that ACP and GCA are homologous lesions.

Ameloblastoma↗
PubMed1997

Thrombin inhibits atrial natriuretic peptide receptor activity in cultured bovine endothelial cells.

Thrombin and the atrial natriuretic peptide (ANP) possess a number of functionally antagonistic properties in vascular endothelial cells. Thus, regulatory interactions that modulate the activity of one or the other could have important sequelae with regard to cardiovascular homeostasis. Thrombin treatment effected a dose- and time-dependent reduction in ANP receptor activity (maximal 70% to 80% inhibition) in cultured bovine aortic endothelial cells. This resulted from a decrease in total receptor number as well as a modest reduction in the affinity of the receptor for its ligand. The inhibition was largely confined to the type C receptor population, in that thrombin had no effect on maximal type A receptor-linked cGMP accumulation. The protein kinase C-activating phorbol ester 12-O-tetradecanoylphorbol 13-acetate effected a similar reduction in binding activity; however, suppression of protein kinase C activity did not reverse the thrombin effect. Pretreatment of endothelial cells with cycloheximide did not completely prevent the thrombin-dependent inhibition, and thrombin did not effect a reduction in type C receptor mRNA levels, findings that argue for a postsynthetic inhibitory locus. The inhibition of receptor activity was effectively irreversible in that suspension of protein synthesis blocked the recovery of receptor density on the cell surface. Reduction in type C receptor density was accompanied by modest increases in the stability of ANP in the culture medium and enhancement of the cellular cGMP response to the peptide, particularly at low ligand concentrations. These findings demonstrate a potentially important interaction between these two agonist systems in regulating endothelial cell function within the vascular wall.

Amino Acid Chloromethyl Ketones↗
PubMed1997

Recent advances in multiple endocrine neoplasia syndromes.

The MEN syndrome are autosomal-dominant disorders of endocrine tissues, characterized by tumor development and in many instances, hormonal hypersecretory states. The genetic lesion in MEN I appears to involve a tumor suppressor locus on the long arm of chromosomes 11 but the identity of the affected gene and its role in contributing to dysregulation of endocrine cell function remain unknown. The lesion in MEN II has been localized to the RET protooncogene locus in the pericentromeric region of chromosome 10. This putative single transmembrane-domain, tyrosine kinase-linked receptor is selectively mutated to produce a constitutively activated protein and presumably an undampened growth-promoting signal to the target cell. Additional studies focused on these genes and their products should facilitate the screening and treatment of patients affected with these disorders and, potentially, provide more information about the role that these genes play in the normal growth and development of endocrine tissues. Such information should prove valuable in deciphering the pathogenetic mechanisms underlying the development of the more common sporadic endocrine tumors.

Diagnosis, Differential↗
PubMed1997

Ras inhibits Jun-activated human atrial natriuretic peptide gene transcription in cultured ventricular myocytes.

p21ras is a potent regulator of myogenic cell growth and differentiation. It has been implicated as playing a major role in the genesis of cardiac hypertrophy. We examined the effect of Ras overexpression on human atrial natriuretic peptide (hANP) gene expression, a marker of hypertrophy, in neonatal rat ventricular myocytes. Transient transfection of Haras, which expresses an activated form of p21ras, effected a modest stimulation of basal hANP-chloramphenicol acetyl transferase (hANPCAT) expression. Noteworthy, the same construct inhibited both c-Jun- and Jun B-stimulated hANPCAT activity (60% and 80%, respectively). Cotransfection of a dominant-negative Ras mutant reversed this inhibition completely. The inhibitory effect was promoter selective in this system. Of those tested, only the hANP and cardiac troponin T promoters were suppressed by Ras. The inhibitory effect appears to operate through a Ras-mediated increase in c-Fos activity as evidenced by (1) the absence of additivity of the Ha-Ras- and c-Fos-mediated inhibition at higher levels of proto-oncogene expression, (2) Ras-dependent activation of c-fos gene transcription, inferred from the induction of a c-fos chloramphenicol acetyl transferase reporter (3.4-fold), and (3) reversal of Ras inhibition by a c-fos antisense oligonucleotide but not by a scrambled DNA sequence of identical base composition or the complementary sense oligonucleotide. Our findings suggest that p21tas can exert a wide range of effects on the phenotype of the cardiac ventricular myocyte. The direction that these effects take appears largely to be a function of the preexisting activation state of the cell.

Animals↗
PubMed1996

1,25(OH)2 vitamin D3, and retinoic acid antagonize endothelin-stimulated hypertrophy of neonatal rat cardiac myocytes.

1,25(OH)2 Vitamin D3 (VD3) and retinoic acid (RA) function as ligands for nuclear receptors which regulate transcription. Though the cardiovascular system is not thought to represent a classical target for these ligands, it is clear that both cardiac myocytes and vascular smooth muscle cells respond to these agents with changes in growth characteristics and gene expression. In this study we demonstrate that each of these ligands suppresses many of the phenotypic correlates of endothelin-induced hypertrophy in a cultured neonatal rat cardiac ventriculocyte model. Each of these agents reduced endothelin-stimulated ANP secretion in a dose-dependent fashion and the two in combination proved to be more effective than either agent used alone (VD3: 49%; RA:52%; VD3 + RA:80% inhibition). RA, at concentrations known to activate the retinoid X receptor, and, to a lesser extent, VD3 effected a reduction in atrial natriuretic peptide, brain natriuretic peptide, and alpha-skeletal actin mRNA levels. Similar inhibition (VD3:30%; RA:33%; VD3 + RA:59% inhibition) was demonstrated when cells transfected with reporter constructs harboring the relevant promoter sequences were treated with VD3 and/or RA for 48 h. These effects were not accompanied by alterations in endothelin-induced c-fos, c-jun, or c-myc gene expression, suggesting either that the inhibitory locus responsible for the reduction in the mRNA levels lies distal to the activation of the immediate early gene response or that the two are not mechanistically coupled. Both VD3 and RA also reduced [3H]leucine incorporation (VD3:30%; RA:33%; VD3 + RA:45% inhibition) in endothelin-stimulated ventriculocytes and, once again, the combination of the two was more effective than either agent used in isolation. Finally, 1,25(OH)2 vitamin D3 abrogated the increase in cell size seen after endothelin treatment. These findings suggest that the liganded vitamin D and retinoid receptors are capable of modulating the hypertrophic process in vitro and that agents acting through these or similar signaling pathways may be of value in probing the molecular mechanisms underlying hypertrophy.

Animals↗
PubMed1996

Some current concepts on the pathology of ameloblastomas.

This article describes some fundamental concepts and new developments in the pathologic characteristics of ameloblastoma. The former include (1) the necessity of separating ameloblastomas into three clinical types, namely the solid or multicystic (the classic intraosseous ameloblastoma), the unicystic, and peripheral varieties; (2) the importance of the tumor's location in the jaws; and (3) the manner in which cancellous and compact bone of the jaws affect the spread of ameloblastomas. New developments discussed include the desmoplastic ameloblastoma, the clear cell ameloblastoma, the recognition of the so-called acanthomatous epulis in dogs as a fairly common spontaneous animal model of ameloblastoma, and some work concerning therapeutic irradiation of ameloblastomas. Additional topics include the problems involved in the early microscopic diagnosis of ameloblastoma and of ameloblastic carcinoma and our lack of knowledge concerning the cause of ameloblastomas.

Ameloblastoma↗
PubMed1996

Ameloblastic fibromas and related tumors in cattle.

This article concerns rare odontogenic tumors that occur predominantly in the mandibular incisor region of young cattle and which have often in the past been referred to as ameloblastomas, or as the outdated synonym, adamantinoma. Twenty-two examples from the literature and two new ones were studied. Six consisted of epithelial islands which resembled those of ameloblastoma but which were located within a cellular fibrous connective tissue that was the second component of the tumor; these mixed odontogenic tumors therefore represented ameloblastic fibromas, not ameloblastomas. Eight consisted of a combination of ameloblastic fibroma and odontoma and therefore were ameloblastic fibro-odontomas, and one was apparently malignant (ameloblastic fibro-odontosarcoma). Excluding this last lesion, these tumors should respond well to enucleation, like their human counterparts but, to confirm this hypothesis, the margins of future examples should be carefully examined to determine that they are well-demarcated, not invasive. The microscopic features of the remaining 9 tumours could not be evaluated adequately, while another 17 tumors in cattle and water buffalo reported briefly could not be studied to any extent because of insufficient information.

Ameloblastoma↗
PubMed1996

Epulides in the dog: a review.

This article is based on a review of the literature and the study of pathology sections obtained from various veterinary pathology laboratories. Epulis is a non-specific, clinical designation for a localized, exophytic growth on the gingiva. Four reactive epulides occur in human beings, namely focal fibrous hyperplasia (fibrous epulis), pyogenic granuloma, peripheral giant cell granuloma (giant cell epulis), and peripheral ossifying fibroma (calcifying fibrous epulis). The first three also occur in dogs but only focal fibrous hyperplasia appears to be common. The peripheral ossifying fibroma has not yet been reported in dogs. Odontogenic tumors occurring on the gingiva (i.e., as epulides) are referred to as peripheral odontogenic tumors. Three types have been reported in dogs. One, the common fibromatous epulis, is equivalent to the rare peripheral odontogenic fibroma in human beings. Another, the acanthomatous epulis, appears to be a form of ameloblastoma but differs from the peripheral ameloblastoma in human beings in that it invades bone; its biological behavior is therefore that of the human intraosseous ameloblastoma. The third, a rare lesion, has been referred to in the veterinary literature as a calcifying epithelial odontogenic tumor, although it is not the canine counterpart of the human CEOT. The term, amyloid-producing odontogenic tumor, has been suggested as being appropriate for this lesion.

Ameloblastoma↗
PubMed1996

Central odontogenic fibroma current concepts.

The author reviews current knowledge concerning the central odontogenic fibroma, which at present in incompletely understood, and reaches the following conclusions. 1) The separation of this lesion into simple and WHO types remains valid because they exhibit different histologic features. However, more care should be taken in rendering the diagnosis of the WHO type than in the past; unlike the simple type, it is a fibroblastic lesion. 2) Complex central odontogenic fibroma is a more appropriate term than the WHO type because the WHO does not use the latter term in its 1992 manual. 3) The microscopic distinction of simple odontogenic fibroma from desmoplastic fibroma remains difficult in some cases. 4) The granular cell odontogenic tumor, which has sometimes been referred to as a type of odontogenic fibroma, is a separate entity, although some simple odontogenic fibromas exhibit scattered granular cells. 5) The separation of lesions that have been reported recently as odontogenic fibromas with giant cell reactions from central giant cell granulomas that exhibit foci of odontogenic epithelium requires further study.

Diagnosis, Differential↗
PubMed1996

Spontaneous squamous cell carcinomas of the oral region in domestic animals: a review and consideration of their relevance to human research.

Spontaneous squamous cell carcinomas of the oral region in domestic animals have the potential of providing additional information about the pathology of oral cancer and may be useful in therapeutic research. Moreover, they exhibit definite advantages over chemically induced tumors in rodents. This article provides background information on spontaneous oral squamous cell carcinomas in dogs, cats, cattle, horses and sheep and then discusses the use in research of such tumors in dogs and cats. These two species are potentially the most useful because they are numerous, suffer quite commonly from squamous cell carcinoma of the oral cavity and oropharynx, and are usually allowed to live approximately normal life spans. Moreover, they are being treated routinely in veterinary hospitals.

Animals↗