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Biomedical subjects

R M Graham

Publications and source records attributed to R M Graham.

At least 145 records · Page 8Linked to original sources
PubMed1985

Intercellular canaliculi in eccrine sweat glands: an immunoperoxidase study.

Using an indirect immunoperoxidase technique, both epithelial membrane antigen and carcinoembryonic antigen were identified within the ducts and secretory coils of the eccrine sweat gland. Antibodies to epithelial membrane antigen stained the intercellular canaliculi of the secretory coils, as did those antisera to CEA which showed activity against normal cross-reacting antigen (CEX, NCA). Those without such activity showed minimal or no staining of intercellular canaliculi. There is a difference in antigenic expression between the acinar cells and their intercellular canaliculi, and the cells of eccrine ducts.

Carcinoembryonic Antigen↗
PubMed1985

Role of muscle mass and mode of contraction in circulatory responses to exercise.

The roles of the mode of contraction (i.e., dynamic or static) and the active muscle mass as determinants of the cardiovascular responses to exercise were studied. Six healthy men performed static handgrip (SHG), dynamic handgrip (DHG), static two-knee extension (SKE), and dynamic two-knee extension (DKE) to local muscular fatigue in approximately 6 min. Increases in mean arterial pressure were similar for each mode of contraction, 29 +/- 5 and 30 +/- 3 mmHg in SHG and DHG and 56 +/- 2 and 48 +/- 2 mmHg in SKE and DKE (P greater than 0.05) but larger for KE than HG (P less than 0.001). Cardiac output increased more for dynamic than for static exercise and for each mode more for KE than HG (P less than 0.001). Systemic resistance was lower for dynamic than static exercise and fell from resting levels by approximately 1/3 during DKE. The magnitude of the pressor response was related to the active muscle mass but independent of the contraction mode. However, the mode of contraction affected the circulatory changes contributing to the pressor response. Equalization of the pressor responses was achieved by proportionately larger increases in cardiac output during dynamic exercise.

Adult↗
PubMed1985

Rapid reciprocal changes in adrenergic receptors in intact isolated hepatocytes during primary cell culture.

In hepatocytes freshly isolated from adult female rat livers, catecholamine-stimulated glycogenolysis is mediated predominantly by alpha 1-adrenergic receptors, and to only a minimal extent by beta 2 receptors. Primary cell culture of these hepatocytes results in a switch in the adrenergic control of glycogenolysis from an alpha 1 to a predominant beta 2 type of response. To investigate whether this switch is due to an alteration in the plasma membrane receptor composition, we characterized alpha 1 and beta 2-adrenergic receptors in both freshly isolated and cultured hepatocytes, using radioligand-binding techniques. Binding of the selective alpha 1-adrenergic antagonist [3H]prazosin and the beta-adrenergic antagonist [125I]pindolol to intact freshly isolated hepatocytes was of high affinity, saturable, and of appropriate specificity for an alpha 1- and beta 2-adrenergic receptor, respectively. Equilibrium binding studies evaluated by a computer-assisted curve-fitting procedure indicated interaction with a single class of high affinity sites for radiolabeled prazosin (KD = 126 +/- 10 pM; Bmax = 93,000 +/- 5,500 sites/cell) and pindolol (KD = 66 +/- 6 pM; Bmax = 2,000 +/- 700 sites/cell). In intact hepatocytes and in membranes prepared from these hepatocytes, competitive inhibition curves revealed the coexistence of two different sites with high and low affinities for agonists at both alpha 1- and beta 2-adrenergic receptors. When isolated hepatocytes were kept in monolayer cell culture for up to 72 hr, the switch in adrenergic control of glycogenolysis (phosphorylase a activation) from an alpha to a beta pathway was confirmed and was associated with a progressive decrease in the number of alpha 1 receptors and an increase in beta 2-adrenergic receptor density, without marked change in the affinity of agonists or antagonists. To investigate the mechanism(s) of this reciprocal change, a number of perturbations were examined including alterations in the composition of the culture medium and the influence of various hormones and inhibitors of cellular function. De novo protein synthesis is implicated in both receptor alterations as the inhibitors cycloheximide and actinomycin D prevented the increase in beta- and attenuated the decrease in alpha-adrenergic sites. The other perturbations were without effect. Thus, these studies provide evidence for a coupling of the functional alteration in glycogenolysis to changes at the receptor level per se. The mechanism underlying the reciprocal changes in hepatocyte adrenergic receptors during culture remains undefined.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Photoaffinity labeling of the alpha 1-adrenergic receptor using an 125I-labeled aryl azide analogue of prazosin.

alpha 1-Adrenergic receptor probes, which can be radioiodinated to yield high specific activity radioligands, have been synthesized and characterized. 2-[4-(4-Amino-benzoyl)piperazin-1-yl]-4-amino-6,7-dimethoxyquin azoline (CP63,155), an arylamine analogue of the selective alpha 1-adrenergic antagonist prazosin, and its iodinated derivative, 2-[4-(4-amino-3-[125I]iodobenzoyl)piperazin-1-yl]-4-amino-6, 7-dimethoxyquinazoline [( 125I]CP63,789), bind reversibly and with high affinity (KD = 1 nM and 0.6 nM, respectively) to rat hepatic membrane alpha 1-adrenergic receptors. Conversion of [125I]CP63,789 to the aryl azide yields a photolabile derivative, 2-[4-(4-azido-3-[125I]iodobenzoyl)piperazin-1-yl]-4-amino-6, 7-dimethoxyquinazoline [( 125I]CP65,526), which prior to photolysis binds competitively and with high affinity (KD = 0.3 nM). Binding of [125I]CP63,789 and [125I]CP65,526 (prior to photolysis) is rapid and saturable. Both ligands identify similar alpha 1-adrenergic receptor binding site concentrations as the parent probe, [3H]prazosin. Specific binding by these iodinated ligands is stereoselective and inhibited by a variety of adrenergic agents with a specificity typical of the alpha 1-adrenergic receptor. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography of [125I]CP65,526-labeled rat hepatic membranes reveal major protein species with molecular weights of 77K, 68K and 59K. Each protein binds adrenergic ligands with stereoselectivity and with a specificity typical of the alpha 1-adrenergic receptor. Inclusion of multiple protease inhibitors during membrane preparation prior to SDS-PAGE does not alter the labeling of these peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗
PubMed1984

The structure of rat preproatrial natriuretic factor as defined by a complementary DNA clone.

The structure of rat preproatrial natriuretic factor ( preproANF ) was determined by nucleotide sequence analysis of an ANF complementary DNA clone. PreproANF is composed of a hydrophobic leader segment (20 amino acids), a precursor containing one glycosylation site (106 amino acids), and ANF (24 amino acids). Atrial natriuretic factor is located at the carboxyl terminus of the precursor molecule. The human, mouse, and rat genomes each contain a single ANF gene which is highly conserved.

Animals↗
PubMed1984

Selective alpha 1-adrenergic antagonists: therapeutically relevant antihypertensive agents.

Alpha-adrenergic antagonists were the first substances to receive serious consideration as antihypertensive agents. However, their therapeutic potential in the management of essential hypertension was not realized until prazosin, a highly selective alpha 1-adrenergic antagonist, became available. A number of analogs of prazosin have now been synthesized, as have several structurally distinct alpha 1-adrenergic antagonists. Preliminary investigations suggest that these agents may also be clinically useful antihypertensive drugs. The alpha 1 receptor of arteriolar smooth muscle is the predominant adrenergic subtype determining sympathetically mediated vascular tone. Therefore, its selective blockade by an agent such as prazosin is a relevant approach to the major pathophysiologic defect in hypertension: an elevation of peripheral vascular resistance. Because prazosin has little selectivity for the alpha 2 receptor, the negative feedback control of norepinephrine release from sympathetic nerve terminals remains intact. This unique action of prazosin may explain why it effectively lowers arterial pressure without markedly increasing cardiac output, heart rate and plasma renin activity. An additional factor in the favorable therapeutic effects of this agent is its ability to induce a balanced reduction in both arteriolar and venous tone, with little change or even improvement in renal hemodynamics. The antihypertensive effects of prazosin, when used as a single agent, may be modest. However, it may be useful as initial as well as adjunctive therapy for the management of hypertension because of its high toxic to therapeutic ratio, coupled with a sustained reduction in arterial blood pressure, a low incidence of side effects, and a potentially favorable metabolic profile.

Adrenergic alpha-Antagonists↗
PubMed1984

Epithelial markers in primary skin cancer: an immunoperoxidase study of the distribution of epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA) in 65 primary skin carcinomas.

Sixty-five primary malignant skin tumours have been stained for carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) using rabbit polyclonal affinity-purified antibodies and an indirect immunoperoxidase technique. The tumours consisted of 15 invasive squamous carcinomas, 23 basal cell carcinomas, 16 malignant eccrine poromas (porocarcinomas), and 11 sebaceous carcinomas. The basal cell carcinomas were negative for CEA and EMA except where there was keratotic or sebaceous differentiation. All the sebaceous and squamous carcinomas and 15/16 porocarcinomas contained EMA. 12/15 squamous carcinomas were positive for CEA. The malignant poromas were negative for CEA except on the ulcerated surface of two. In tumours classified as sebaceous carcinomas there was positive staining for CEA in some cells, cyst contents and/or keratotic foci. These findings have implications for the use of immunoperoxidase localization of epithelial markers in the differential diagnosis of primary and metastatic skin cancer.

Adenocarcinoma↗