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D K Granner

Publications and source records attributed to D K Granner.

At least 163 records · Page 9Linked to original sources
PubMed1980

Glucocorticoid hormones increase the activity of plasma membrane alkaline phosphodiesterase I in rat hepatoma cells.

In rat hepatoma cells the synthetic glucocorticoid dexamethasone causes a 3-fold increase in the activity of the plasma membrane enzyme alkaline phosphodiesterase I (oligonucleat 5'-nucleotidohydrolase, EC 3.1.4.1). The data are consistent with an induction phenomenon mediated by the glucocorticoid receptor involved in tyrosine aminotransferase induction. The effect on alkaline phosphodiesterase I is not a reflection of a general membrane effect of dexamethasone, because the activity of three other enzymes of the plasma membrane is unaffected. On the other hand, nucleoside diphosphatase (nucleoside diphosphate phosphohydrolase acting on ADP) activity is inhibited. Thus, two more enzymes sensitive to glucocorticoids have been identified in a cell line in which these hormones influence only very few gene products. This paper describes enzymatic changes in the plasma membrane of rat hepatoma cells in which glucocorticoids normalize a number of membrane-associated processes that are considered to be characteristic of transformed cells.

Animals↗
PubMed1979

The role of glucocorticoid hormones as biological amplifiers.

Recent research in hormone action has been aimed at studying single effects in well-defined systems. As exemplified in several chapters of this book, it has been possible to deduce a general mechanism of action of the glucocorticoids using this approach. Most hormones, and the glucocorticoids in particular, do not act as independent agents in the intact animal. Although the best known example of how glucocorticoids interact with other hormones is the amplification of the effect of those whose action is mediated by cAMP, these steroids also augment the effects of a variety of other hormones and effectors. Such interactions are of interest in clinical medicine as well, since glucocorticoid hormones are used in combination with other drugs in a number of conditions, including the treatment of asthma, allergies, and certain kinds of shock and cancer. Neither the biochemical nor the pharmacologic basis for the effects of the glucocorticoids is known. In some cases the actions of other hormones are not observed unless the tissue has first been exposed to glucocorticoids. In these instances the glucocorticoids are said to exert a "permissive effect," since they allow a process to proceed at a maximal rate even though the steroid itself has no effect on this process. There is no doubt that such examples exist, as documented above: thus the concept of a "permissive effect" does have utility. The term fails to describe the more general role the glucocorticoids play, since in many instances the steroid also has a direct effect on the process itself, or optimizes a process in which the primary effector is not as yet known. Because of these cases, and because the historically more general usage first proposed by INGLE [1] seems to have been forgotten, use of the term "permissive effect" has been avoided in this chapter. An ultimate goal in glucocorticoid hormone research is to identify the mechanisms involved in the amplification effect these hormones exert. Now that the actions of these hormones and of the hormones they interact with are being defined, such work is within the realm of feasibility.

Animals↗
PubMed1979

Unlinked control of multiple glucocorticoid-induced processes in HTC cells.

HTC cell variants chosen for their lack of tyrosine aminotransferase (EC 2.6.1.5) (TAT) induction by glucocorticoids were tested for interrelated effects on other glucocorticoid responses: TAT induction by dibutyryl cyclic AMP (dBcAMP) +/- dexamethasone, glutamine synthetase (GS) induction, cyclic nucleotide phosphodieterase (PDE) suppression, inhibition of alpha-aminoisobutyric acid (AIB) uptake, inhibition of plasminogen activator (PA), and induction of mouse mammary tumor virus (MTV). Loss of TAT induction by steroid was accompanied by loss of TAT induction by dBcAMP and of PDE suppression by steroid. In addition, subclones of MTV-infected cells were examined for the effect of the virus on glutamine synthetase (GS) and TAT induction. The virus had no effect on their induction in wild-type cells and no effect on GS induction in the variants. One MTV-infected subclone from a TAT variant, however, showed significant return of TAT induction.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Pathogenesis of prolactin-secreting pituitary adenomas.

42 women with amenorrhoea and hyperprolactinaemia had trans-sphenoidal surgery and resection of histologically verified pituitary adenomas. 74% of these patients developed amenorrhoea and/or galactorrhoea in immediate association with the use or discontinuation of oral contraceptives or post partum. There was enough adenomatous tissue for immunocytochemical studies in 35 specimens and specific localisation of prolactin was possible in 31. There is evidence that about 10% of the population have small pituitary tumours, and the majority of these tumours, though asymptomatic, are potentially prolactin-secreting. It is suggested that oestrogens, which are known to modulate prolactin secretion in normal human beings and in animals, can induce the growth and expression of otherwise silent pituitary lesions and that this should be considered a risk of oral-contraceptive use.

Adenoma↗
PubMed1978

Diagnosis of occult familial medullary carcinoma of the thyroid using pentagastrin.

Medullary carcinoma of the thyroid is unique in that it can often be diagnosed solely on the basis of abnormally high basal serum thyrocalcitonin levels. Two brothers described in this report were found to have normal basal serum thyrocalcitonin levels when examined after another family member died from metastatic medullary carcinoma of the thyroid. Pentagastrin, a synthetic analog of gastrin, was subsequently administered to these two high-risk relatives and found to stimulate the release of thyrocalcitonin to abnormally high levels. They were found to have occult medullary carcinoma of the thyroid. Eight other first-degree relatives of the deceased patient with normal basal serum thyrocalcitonin levels were screened with pentagastrin and found to have normal stimulated levels of thyrocalcitonin. This report reinforces the need to recognize that medullary carcinoma of the thyroid can be familial and that physicians are obligated to screen asymptomatic kin who are at high risk. We recommend that all susceptible relatives, even if they have normal basal serum thyrocalcitonin levels, undergo the provocative pentagastrin test with repeat annual testing if necessary. In addition, the provocative pentagastrin test can be used to follow up patients who have undergone thyroidectomy.

Adolescent↗
PubMed1977

Interaction of glucocorticoid hormones and cyclic nucleotides in induction of tyrosine aminotransferase in cultured hepatoma cells.

Reproducible induction of the enzyme tyrosine aminotransferase by dibutyryl cAMP (Bt2cAMP) in a line of HTC hepatoma cells in suspension culture requires that the cells be preinduced with dexamethasone, a synthetic glucocorticoid which itself induces tyrosine aminotransferase. Concentrations of dexamethasone that do not induce tyrosine aminotransferase fail to support Bt2cAMP induction, removal of the steroid from the medium leads to a loss of the Bt2cAMP effect, and an HTC cell line whose aminotransferase is not steroid-inducible does not respond to the cyclic nucleotide. We show that the further induction of tyrosine aminotransferase by Bt2cAMP in dexamethasone-treated cells is due to an increased rate of enzyme synthesis. The cyclic nucleotide has no effect on aminotransferase synthesis in cells grown in the absence of steroid. Several lines of evidence suggest that dexamethasone acts at a step beyond the activation of protein kinase by cAMP: (a) basal levels of cAMP are not altered by growth of HTC cells in dexamethasone; (b) accumulation of cAMP from the medium is not enhanced; (c) the glucocorticoid does not induce cAMP-dependent protein kinase in HTC cells; and (d) there is no augmentation of cAMP binding to the regulatory protein, nor is there any change in cAMP activation of protein kinase caused by growth in dexamethasone. These results help define a system that should be useful in studying the interaction of cyclic nucleotides and steroid hormones.

Bucladesine↗
PubMed1977

Myasthenia gravis and Schmidt syndrome.

A patient with myasthenia gravis developed both Addison disease and primary hypothyroidism, with demonstrable anti-adrenal and antithyroid antibodies in her serum. The association of myasthenia gravis with Schmidt syndrome does not seem to be a chance occurrence, considering the autoimmune pathogenesis of each of these disorders.

Addison Disease↗
PubMed1977

Sputum cytology: a valuable addition to the investigation of hypercalcemia.

In this paper we report two patients with asymptomatic hypercalcemia, one with primary and the other with ectopic hyperparathyroidism, in whom cytologic examination of the sputum led to the diagnosis of carcinoma of the lung despite the presence of normal chest roentgenograms. Sputum cytology is a simple, inexpensive and accurate test which should be included in the diagnostic regimen for hypercalcemia.

Carcinoma, Squamous Cell↗
PubMed1976

Relationship between chromosome condensation and metaphase lysine-rich histone phosphorylation.

Treatment of metaphase HTC cells with ZnCl2 inhibits histone phosphatase activity and leads to an increase in the hyperphosphorylated forms of the lysine-rich (F1) histone. Under normal conditions a massive phosphatase activity is triggered as the cells shift from M into G1 phase. In the presence of ZnCl2 this activity is abolished and thehyperphosphorylated form of F1 persists intact into G1. We have asked the simple question of whether the chromosome can still extend during the M-G1 transition even if the F1 histone is maintained in the hyperphosphorylated form. We observe an apparently normal extension os the chromosomal material under these conditions, though it is evident that high levels of ZnCl2 have rather substantial effects on other cell functions.

Cell Division↗
PubMed1975

Studies on highly metabolically active acetylation and phosphorylation of histones.

The capacity to effectively label tumor cell hostones using very short pulses of [3-H]acetate and [32-P]phosphate (1 to 10 min) has been developed. Four histone fractions F3, F2a1, F2a2, and F2b are extensively acetylated in short time periods. About 70% of the acetate accumulated on the histone during a short pulse is removed with a half-life of similar to 3 min. The rest of the metabolically active acetate is removed with a half-life of 30 to 40 min. Histones F2a1, F2a2, and F1 are acetylated at the NH2 terminus and this modification is metabolically stable. In short pulses, histones are labeled with 32-P in the order F2a2 greater than F1 greater than F3 greater than F2a1 greater than F2b. All fractions have a fairly rapid turnover time (t1/2 similar 20 to 40 min) except F1 phosphate which turns over some 5 times more slowly.

Acetates↗
PubMed1975

Deposition of histones onto replicating chromosomes.

The mode of distribution of newly synthesized and pre-existing histones has been studied during the process of chromosome replication. Newly synthesized histone was labeled with [3H]lysine and newly synthesized DNA was density labeled with iododeoxyuridine. The histone was covalently linked to DNA, and radiolabeled histone was analyzed on CsCl density gradients. We have defined conditions that do not give rise to histone randomization during isolation, and also developed a method of defining the distribution of histones in chromatin on a density gradient in the unavoidable presence of nonhistone protein. Three possible modes of distribution of histone onto the replicating chromosome can be conceived; we describe experiments designed to distinguish unequivocally among these possibilities and conclude that histones are deposited randomly onto the chromosome.

Carcinoma, Hepatocellular↗