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Biomedical subjects

D G Gardner

Publications and source records attributed to D G Gardner.

At least 127 records · Page 7Linked to original sources

Insulin regulation of rat growth hormone gene expression.

Insulin has been shown previously to inhibit basal and glucocorticoid- or T3-stimulated rat GH (rGH) synthesis, secretion, and mRNA levels in cultured rat pituitary tumor cells (GH3 cells) or pituitaries. The effects of insulin on rGH gene expression in GH3 cells were examined in greater detail in the current studies. Cells were deinduced for 5 days in medium devoid of steroids, T3, and insulin. Cells were then treated for 48 h with insulin (5 X 10(-9) M), dexamethasone (Dex; 10(-6) M), T3 (10(-8) M), insulin plus Dex, or insulin plus T3. When media and hormones were not replaced daily the results were similar to those obtained previously. Insulin decreased both basal and glucocorticoid-stimulated rGH mRNA levels to approximately 70% of control levels, as measured by cytoplasmic dot hybridization. By contrast, when media and hormones were replaced daily, rGH mRNA levels increased by 1.5 to 7-fold in response to insulin in the absence or presence of Dex or T3, measured by both cytoplasmic dot hybridization and RNA (Northern) blotting. Dex increased rGH mRNA levels under both sets of conditions, verifying the specific nature of the insulin influence. Maximum rGH gene expression was achieved after a 48-h exposure to insulin. The observed insulin effects were probably mediated through insulin rather than insulin-like growth factor I or II receptors, since the concentration of insulin employed was near the Kd of the hormone for its receptor measured in the same cells. These results suggest that insulin is capable of regulating rGH gene expression. The action of insulin can be either positive or negative and is influenced by the metabolic state of the cell.

Animals↗

Glucocorticoid control of rat growth hormone gene expression: effect on cytoplasmic messenger ribonucleic acid production and degradation.

The effect of the glucocorticoid dexamethasone on the production and degradation of rat GH (rGH) cytoplasmic mRNA was studied in cultured rat pituitary tumor (GC) cells. The incorporation of [3H]uridine into both rGH cytoplasmic mRNA and the pyrimidine nucleotide precursor pool was determined in hormone-treated and control cells. From these measurements glucocorticoid effects on absolute production rates of rGH cytoplasmic mRNA were determined and compared to effects on rGH mRNA accumulation. Rat GH mRNA half-life was then calculated based on a first-order decay model. Rat GH mRNA half-life was also directly assayed by: 1) pulse-chase studies and 2) measuring the kinetics of decay of rGH mRNA in cells after transfer from serum-containing to hormone-deficient media. From these independent analyses rGH mRNA half-life estimates ranged from 28-55 h in different experiments. Within individual experiments there was little variability of rGH mRNA decay rates; glucocorticoids were found not to alter the stability of rGH cytoplasmic mRNA. Glucocorticoid induction of rGH cytoplasmic mRNA accumulation was accounted for solely on the basis of increased mRNA production.

Animals↗

Thyroid hormone increases rat atrial natriuretic peptide messenger ribonucleic acid accumulation in vivo and in vitro.

Thyroid hormone has a number of effects on cardiovascular and renal function which are shared by the atrial natriuretic peptide (ANP). We attempted to demonstrate a relationship between the two by studying the effects of thyroid hormone on the expression of the ANP gene and the secretion of its encoded protein. Thyroid hormone, when given to thyroidectomized rats, increased plasma ANP levels by approximately 2-fold in both watered and dehydrated animals. Cardiac ANP mRNA in dehydrated animals fell to 25% of that in the water-replete controls. T4 increased cardiac ANP mRNA 3-fold in dehydrated animals, but failed to alter ANP mRNA in those animals allowed free access to water. The effect of thyroid hormone appeared to take place, at least in part, at the level of the ANP-synthesizing cardiocyte. T3, at concentrations ranging from 10(-10)-10(-8) M, increased ANP mRNA levels a maximum of 2-fold in primary cultures of neonatal cardiocytes. Both basal and T3-stimulated ANP transcripts appeared to be identical to their counterparts in the adult atria, as assessed by blot hybridization and S1 nuclease analysis. T3 (10(-8) M) also effected a 2-fold increase in media ANP immunoreactivity. These data indicate that thyroid hormone increases the secretion and genetic expression of ANP in vivo and in vitro and suggests a role for the peptide as a mediator of at least some thyroid hormone effects in the cardiovascular system.

Animals↗

Atrial natriuretic peptide mRNA is regulated by glucocorticoids in vivo.

In these studies glucocorticoids were found to increase the plasma levels of atrial natriuretic peptide (ANP) as well as the expression of the ANP gene in the Sprague-Dawley rat. Plasma ANP rose two-fold after 48 hrs. of exposure to dexamethasone (1 mg/day) in both intact and adrenalectomized animals. This was accompanied by a 1.5-2.0 fold increase in the levels of atrial and ventricular ANP transcripts. Deoxycorticosterone acetate (5 mg/day), administered on the same schedule, failed to increase either plasma ANP levels or cardiac ANP mRNA accumulation. These effects suggest that ANP may have a potential role as a mediator of glucocorticoid activity in the cardiovascular system and support the hypothesis that ANP is a glucocorticoid-regulated gene.

Animals↗

Mechanisms of glucocorticoid hormone action.

This report summarizes our studies, in context with the results of other laboratories, of the molecular mechanisms of glucocorticoid hormone action. The receptors for these steroids are comprised of single polypeptide chains of about 90,000 molecular weight. Binding of agonist steroids to the receptor induces a conformational change to an active receptor form that is followed by a second change in the glucocorticoid-receptor complex, termed activation, that alters the charge of the complex and results in its binding to specific sites on the DNA termed glucocorticoid regulatory elements (GREs). The GRE on the human metallothionein-IIA gene is located in the 5'-flanking DNA. It can function independently of the gene's promoter, and when ligated upstream from the herpes simplex virus (HSV) thymidine kinase (TK) gene promoter, can activate it. The binding of the glucocorticoid-receptor complex to the GRE probably alters chromatin structure over a limited span to facilitate RNA polymerase action. The regulation by glucocorticoids of growth hormone gene expression is more complex. The steroid appears to elicit both transcriptional and posttranscriptional influences that are also affected by thyroid hormone. Also the glucocorticoid influences appear to be exerted in part through DNA structures located downstream from the transcriptional initiation site. A GRE has been defined in intron A of the hGH gene through gene transfer and DNA binding experiments. Finally, gene transfer experiments suggest that pituitary-specific factors influence the ability of glucocorticoids to affect GH gene expression.

Adenosine Triphosphate↗

A method of distinguishing between amalgam and graphite in tissue.

The clinical and histologic appearance of amalgam and graphite tattoos are similar; both appear as dark particles, although amalgam, after degradation, displays a characteristic binding to blood vessels, nerves, basement membrane, and fibers. Graphite particles also consistently exhibit a light yellow peripheral birefringence under strong polarized light. Amalgam particles may exhibit a similar birefringence, but often it is weak or absent. When histologic sections containing particles exhibiting birefringence are treated with 10% ammonium sulfide solution, graphite is unaltered, whereas the birefringence of amalgam particles, if present, is changed to orange, or the particles undergo dissolution.

Animals↗

Mucoceles of the maxillary sinus.

Antral mucoceles are a separate entity that must be distinguished from the common, dome-shaped lesions of the floor of the sinus that are also often, although inaccurately, referred to as mucoceles. The latter lesions are known by a variety of names, including pseudocysts, and are innocuous. True antral mucoceles are potentially destructive lesions that are often secondary to trauma, especially the Caldwell-Luc procedure. This article describes in some detail the clinical, radiologic, and histopathologic features of true antral mucoceles. One type of antral mucocele, commonly seen in Japan, is referred to as a postoperative maxillary cyst and is identical to the surgical ciliated cyst of the maxilla originally reported by Gregory and Shafer.

Aged↗

Extra-atrial expression of the gene for atrial natriuretic factor.

Atrial natriuretic factor (ANF) is a group of peptides, originally isolated from the cardiac atria, that have a number of important effects on blood pressure, renal function, and salt balance. In the current study, expression of the ANF gene in certain extra-atrial tissues of the rat has been examined by radioimmunoassay of extracted ANF protein and by blot-hybridization, nuclease S1 analysis, and primer-extension analysis of the ANF mRNA. ANF peptides and mRNA were detected in cardiac ventricles, lung, and pituitary gland at levels generally less than or equal to 1% those of cardiac atria. The ANF transcripts in extra-atrial tissue appear to be very similar to those synthesized in the atria. They are polyadenylylated, are equivalent in overall length (950-1050 nucleotides), and have identical 5' termini. A secondary transcription start site mapping approximately 80 base pairs upstream from the primary start site is employed in atria and to a lesser extent in other tissues. The ANF transcript is present throughout the cardiac ventricles from apex to base and in the septum as well as the ventricular free walls. The transcript is more prevalent in the left ventricle and interventricular septum than in the right ventricle. Immunocytochemistry using various anti-rat ANF antibodies localized ANF immunoreactivity to the atrial myocytes; the ventricular myocytes, particularly along the endothelial surface of the ventricular chamber; perialveolar cells in the lung; and the gonadotropin-producing cells of the pituitary. The data indicate that the capacity for ANF gene expression extends beyond atrial tissue, albeit at much reduced levels, and may suggest alternative, perhaps paraendocrine, functions for the peptide in these tissues.

Animals↗

Granular cell reaction to surgical glove powder.

The histopathologic features characteristic of the inflammatory response associated with starch powder used as a lubricant for surgical gloves were investigated by implanting starch granules into 3 separate sites on the right side of 8 male Wistar rats. On the opposite side, a sham-operated site and sites implanted with talc were used as controls. Two rats were killed at 1, 2, 3 & 4-week intervals and tissue from the implanted sites was assessed for distinctive features. It was found that a consistent feature of the starch-implanted sites was the presence of large histiocytes containing prominent PAS-positive, diastase-resistant inclusions. These cells were not found in the control sites and, thus, were considered characteristic of starch contamination in tissue, even in the absence of identifiable starch granules. A possible clinical case of reaction to starch, identified retrospectively, using these results is discussed.

Animals↗

Starch artifacts in oral cytologic specimens.

Starch powder from surgical gloves is a common artifact that may superficially resemble atypical epithelial cells or spores in oral cytologic specimens. This article describes the distinguishing features of starch granules visible under a light microscope and discusses their clinical relevance.

Cheek↗

Plexiform unicystic ameloblastoma. A variant of ameloblastoma with a low-recurrence rate after enucleation.

The term, plexiform unicystic ameloblastoma, refers to a pattern of epithelial proliferation that has been described in dentigerous cysts, primarily in persons in the second and third decades of life and predominantly in the posterior part of the mandible. This article provides the first study on the biologic behavior of these lesions. Of 28 examples treated by enucleation/curettage, and for which adequate follow-up information was obtained, only three recurred. This figure (10.7%) compares very favorably with the 55% to 90% recurrence rate quoted for ameloblastomas of all types that have been treated by curettage and is similar to that found in other types of unicystic ameloblastoma. The plexiform unicystic ameloblastoma is concluded from this study to be an undifferentiated histologic variant of unicystic ameloblastoma and not a separate entity. Enucleation with long-term follow-up information is adequate for tumors that have proliferated into the lumen of the cyst, but more extensive surgery is recommended for those that involve the periphery of its fibrous connective wall. This study has also shown that plexiform unicystic ameloblastomas are not always associated with unerupted teeth, in which case they probably occur over a wider age range than those resembling dentigerous cysts.

Adolescent↗

Pseudocysts and retention cysts of the maxillary sinus.

The dome-shaped radiopaque shadows frequently seen on the floor of the maxillary sinus, and sometimes inaccurately referred to as antral mucoceles, appear to represent focal accumulation of inflammatory exudate that lifts the epithelial lining of the sinus and the periosteum away from the underlying bone to form the characteristically shaped structures. Their histologic appearance is therefore that of normal or inflamed maxillary sinus lining. There is no epithelium-lined cavity present beneath the sinus mucosa; consequently, the term pseudocyst of the maxillary sinus is advocated. Less commonly, epithelium-lined retention cysts, similar to those of the minor salivary glands, are found, but mucoceles of the type found in the oral cavity apparently do not occur in the maxillary sinus.

Connective Tissue↗

The mixed odontogenic tumors.

This article attempts to clarify the interrelationships of the so-called mixed odontogenic tumors. The difficulty in distinguishing histologically between the ameloblastic fibroma and the ameloblastic fibro-odontoma on the one hand and the developing odontoma on the other is emphasized. Also discussed is the desirability of discarding some terms used for histologic variants of ameloblastic fibroma, such as immature dentinoma and ameloblastic fibrodentinoma.

Ameloblastoma↗

The mixed odontogenic tumors.

This article attempts to clarify the interrelationships of the so-called mixed odontogenic tumors. The difficulty in distinguishing histologically between the ameloblastic fibroma and the ameloblastic fibro-odontoma on the one hand and the developing odontoma on the other is emphasized. Also discussed is the desirability of discarding some terms used for histologic variants of ameloblastic fibroma, such as immature dentinoma and ameloblastic fibrodentinoma.

Ameloblastoma↗

Canalicular adenoma: not a basal cell adenoma.

The evidence that canalicular adenomas and basal cell adenomas are separate entities is presented in this article. The clinical features were studied in a series of 13 previously unreported salivary gland tumors (5 canalicular adenomas and 8 basal cell adenomas) and 99 examples derived from the literature (68 canalicular adenomas and 31 basal cell adenomas). Representative tumors from the new cases and from 66 referred cases were studied by histologic, histochemical, and electron microscopic techniques. The two tumors differ significantly with respect to the age range of affected patients, site of predilection, and morphologic and histochemical features.

Adenoma↗

A pathologist's approach to the treatment of ameloblastoma.

There are three clinical types of ameloblastoma: the solid or multicystic type; the unicystic type; and the rare peripheral type. Important considerations in planning treatment include the clinical type as well as the anatomic location of the tumor and the availability of the patient for follow-up examinations. The various histologic patterns exhibited by this tumor have no bearing on its biologic behavior. In this article the treatment of the three types of ameloblastoma is discussed, with emphasis on their biologic behavior and anatomic considerations.

Ameloblastoma↗

Inhibition of parathyroid hormone release from dispersed bovine cells by ouabain.

Ouabain, at concentrations of 3 X 10(-4)-10(-3) M, inhibited secretion of PTH approximately 50% in a freshly dispersed bovine parathyroid cell preparation. This inhibition was found with both unstimulated and secretagogue-stimulated PTH release. Reductions in PTH secretion were found at all concentrations of Ca++ tested between 0.3 mM and 2.0 mM and in the presence of the divalent cation chelators EDTA and EGTA, indicating that extracellular Ca++ is not an absolute requirement for the inhibition. The ouabain inhibition did not appear to be mediated through changes in either adenylate cyclase activity or total cellular cAMP, implying a locus distal to the generation of this cyclic nucleotide. The data suggest that transmembrane potential and/or distribution of monovalent cations across the plasma membrane is important in the maintenance of PTH secretion. The mechanisms involved in this control do not appear to involve extracellular Ca++ directly.

Animals↗