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Biomedical subjects

R C Miller

Publications and source records attributed to R C Miller.

At least 199 records · Page 11Linked to original sources

Oral isotretinoin therapy. Use in a patient with multiple cutaneous squamous cell carcinomas and keratoacanthomas.

An 83-year-old woman with multiple squamous cell carcinomas and keratoacanthomas of the legs was treated with orally administered isotretinoin (13 cis-retinoic acid). Complete regression of the tumors was noted during the initial six-month treatment period. In the subsequent 36 months, four new cutaneous tumors were excised. There have been no recurrences of lesions that regressed while the patient was receiving retinoid therapy.

Administration, Oral↗

Dissociation between endothelium-mediated increases in tissue cGMP levels and modulation of aortic contractile responses.

Both methoxamine and clonidine elicited similar maximal contractions of rat isolated aorta in the absence of endothelium. These contractions were not associated with changes in tissue levels of cGMP or cAMP. In the presence of endothelium maximal methoxamine-induced contractions were not less than those elicited in the absence of endothelium but maximal clonidine-induced contractions were reduced to about 10% of those in the absence of endothelium. However, in the presence of endothelium both methoxamine and clonidine induced similar increases in tissue cGMP levels of about 1.5 to 2 fold; cAMP levels were unchanged. There is therefore a dissociation between endothelium-mediated inhibition of maximal contractile responses and increases in tissue levels of cGMP.

Adrenergic alpha-Agonists↗

Plasmid-phage recombination in T7 infected Escherichia coli.

Recombination between genetically marked T7 bacteriophage and plasmids containing inserts of T7 DNA has been studied in order to gain some insight into the phage recombination process. The results suggest that plasmid-phage recombination requires the products of T7 genes 3 (endonuclease), 4 (DNA primase), 5 (DNA polymerase), and 6 (exonuclease), as has been demonstrated previously for phage-phage recombination. Plasmid replication does not compensate for a complete block in phage polymerase synthesis, suggesting a direct role for this enzyme in recombination, rather than an indirect role, by means of producing replicative structures that are recombinogenic. In most respects, plasmid-phage recombination appears to be similar to phage-phage recombination. The participation of two autonomous, structurally dissimilar, homologues, however, might render certain aspects of the recombination process more amenable to analysis. As examples, the characterization of an apparent marker effect and the demonstration of genetic heterozygotes among the products of plasmid-phage recombination are presented.

DNA Primase↗

Responses of sheep and kitten isolated coronary arteries to some vasoactive agents.

In the present study, the effects of a range of vasoactive agents were assessed in sheep isolated coronary artery strips and in kitten isolated perfused coronary arteries. Both preparations contained muscarinic cholinoceptors. However, these receptors mediated contraction of sheep coronaries while dilatation was seen in the kitten. In sheep arteries, 5-hydroxytryptamine caused increases in resting tone and relaxation of acetylcholine-induced tone, while vasoconstriction was the predominant response in the kitten. Angiotensin increased tone in both preparations, although tachyphylaxis was evident. Conversely, adenosine and ATP caused reductions in tone in both preparations. Alpha-adrenoceptor agonists caused vasodilatation in kitten coronaries and decreased acetylcholine-induced tone in sheep arteries. However, weak contractions were observed in sheep coronaries in the absence of induced tone. Results also indicate that sympatomimetic amines mediate relaxation of sheep coronary arteries via beta 1-adrenoceptors. Sheep coronaries are readily and inexpensively obtained and provide a useful tool for the further study of coronary vascular smooth muscle.

Acetylcholine↗

Potentiating effect of indomethacin on relaxations of sheep isolated coronary artery caused by sympathetic nerve stimulation or exogenous noradrenaline.

Indomethacin, 2.8 microM, potentiated relaxation responses of sheep, isolated, superfused coronary arteries caused by electrical transmural stimulation of sympathetic nerves by 2.3 fold, while responses to exogenous noradrenaline were not significantly altered. A ten fold higher concentration of indomethacin potentiated responses to sympathetic nerve stimulation by 3.4 fold and to exogenous noradrenaline by 1.8 fold. Stimulation-induced efflux of radioactivity derived from 3H-(-)-noradrenaline in sheep coronary arteries was not significantly altered by indomethacin (28 microM). Thus, while indomethacin-induced potentiation of relaxation responses to sympathetic nerve stimulation, was not due to an inhibition of prejunctional actions of prostaglandins, it may involve inhibition of the synthesis of prostaglandins which have post-junctional effects.

Animals↗

Acute yersiniosis and its surgical significance.

During early 1982, an outbreak of yersiniosis occurred in northern Mississippi. Abdominal pain suggestive of appendicitis was a common manifestation, but laparotomy revealed mesenteric adenitis. Yersinia enteritis should enter the differential diagnosis of acute appendicitis.

Acute Disease↗

Enhanced responsiveness of rat isolated aorta to clonidine after removal of the endothelial cells.

With the endothelium present, the maximum response of rat isolated aorta to clonidine was much lower than that to noradrenaline. Removal of endothelium enhanced the response to both adrenoceptor agonists and the clonidine-induced maximum contraction became almost equal to that produced by noradrenaline, although it was much more sensitive to inhibition by flunarizine and nifedipine. These results indicate that clonidine and noradrenaline activate receptors present in the endothelial cells and that these receptors are highly sensitive to clonidine.

Animals↗

Endothelial mediated inhibition of contraction and increase in cyclic GMP levels evoked by the alpha-adrenoceptor agonist B-HT 920 in rat isolated aorta.

In the presence of endothelium maximal contractions of rat aorta preparations evoked by B-HT 920 were about 10% of those evoked in the absence of endothelium. 6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)azepin dihydrochloride (B-HT 920, 0.1 microM to 0.1 mM) induced concentration-dependent contractions of rat aorta in the absence of endothelium. Maximal contractions were comparable in magnitude to those induced by noradrenaline. In the presence of endothelium but not in its absence B-HT 920 (0.1 mM) stimulated an increase in tissue cyclic GMP levels of about 2 fold. Levels of cyclic AMP were unaffected. Removal of endothelium reduced basal tissue levels of cyclic GMP. The guanylate cyclase inhibitor methylene blue (0.5 microM) potentiated B-HT 920-induced contractions in the presence of endothelium and inhibited increases in cyclic GMP. In the presence of endothelium 5,8,11,14-eicosatetraynoic acid (ETYA; 0.1 mM), an inhibitor of both lipoxygenase and cyclo-oxygenase systems, inhibited the B-HT 920-induced increase in cyclic GMP but did not potentiate B-HT 920-induced contractions. ETYA also antagonized B-HT 920-induced contractions in the absence of endothelium. It is concluded that endothelium continuously releases a product or products which influence the smooth muscle. Inhibition of B-HT 920-induced contractions in the presence of endothelium is associated with increased tissue levels of cyclic GMP.

5,8,11,14-Eicosatetraynoic Acid↗

Contractile activity of human coronary arteries and human myocardium in vitro and their sensitivity to calcium entry blockade by nifedipine.

Depolarization (100 mM K+) of acetylcholine, serotonin and prostaglandin (PG) F2 alpha contracted human isolated coronary artery segments. Serotonin was about 10-fold more potent than either acetylcholine or PGF2 alpha, but PGF2 alpha elicited contractions of the greatest magnitude. Serotonin (10 microM) and PGF2 alpha (3 microM) induced rhythmic contractions in the arterial segments. Depolarization-, PGF2 alpha- and serotonin-induced increase in tone was depressed by nifedipine, as was the serotonin- and PGF2 alpha -induced rhythmic activity. The induced rhythmic activity was about 100-fold more sensitive to inhibition by nifedipine than was the induced tonic contraction of the arteries. Depolarization-induced contractions and serotonin-induced rhythmic contractions displayed about equal sensitivity to inhibition by nifedipine. Nifedipine was more potent as an inhibitor of depolarization-induced contractions of arteries than it was as an inhibitor of electrically stimulated trabecular strips of ventricle from the same hearts. The inhibition of isolated coronary artery contraction was obtained within the range of nifedipine concentrations observed in the blood of treated patients.

Acetylcholine↗

The action of tabernanthine on noradrenaline-stimulated contractions and 45Ca movements in rat isolated vascular smooth muscle.

The iboga alkaloid tabernanthine inhibited depolarization (100 mM K+)-induced contractions in aorta and mesenteric arteries in an concentration-dependent manner with the respective IC50 values being about 21 and 7 microM. Contractions elicited by noradrenaline in the mesenteric artery were potentiated by lower concentrations (0.1 and 1.0 microM) of tabernanthine while they were inhibited by higher concentrations (10-100 microM). Tabernanthine produced only inhibition of noradrenaline-elicited responses in aorta and portal vein, the vein being the most sensitive of the vessels to the inhibitory effects of the compound. The magnitude of the spontaneous contractions of the portal vein, the aortic intracellular calcium fraction releasable by noradrenaline and the turnover of calcium in unstimulated aorta were enhanced by tabernanthine. Depolarization-stimulated 45Ca influx and contractions in the aorta were inhibited to a similar extent by tabernanthine and 100 microM virtually abolished the 45Ca influx stimulated by noradrenaline and depolarization. It is concluded that tabernanthine has a calcium entry blocking action but also has other actions related to the turnover of intracellular calcium releasable by noradrenaline.

Alkaloids↗

The detection of viable heritable translocations by chromosome banding procedures.

Ethyl methanesulfonate was tested for its ability to induce viable heritable translocations in progeny of male rats given a single IP injection prior to breeding. Reproductively competent Wistar rats were used as the test animals. Males were treated with either 75 or 150 mg/kg EMS or vehicle control. Neonates were used for primary tissue culture; the fibroblasts were harvested for cytogenetic analysis of chromosomes banded by Giemsa banding procedures. Since the cells examined were somatic cells, it was necessary to karyotype only two to three per neonate to ascertain inherited translocations. A reduction in fertility was observed in males treated with EMS. A statistically significant (p less than 0.05) dose-related increase in heritable translocations was observed in the F1 generation of treated animals.

Animals↗

A recombinant DNA plasmid which inhibits bacteriophage T7 reproduction in escherichia coli.

Escherichia coli plasmids carrying a DNA restriction fragment corresponding to the extreme right end of the T7 bacteriophage genome render cells incompetent to support reproduction of wild-type T7. Processing of intracellular concatemeric phage DNA and cell lysis are perturbed by one such plasmid, pRS148. The results are discussed with reference to the possibility that the right end of the T7 genome encodes a lysis-related function.

DNA Replication↗

Effects of histamine and the histamine antagonists mepyramine and cimetidine on human coronary arteries in vitro.

The effects of histamine have been studied on human isolated coronary artery preparations taken from hearts ranging in age from 9 to 73 years. Histamine in large concentrations (100 microM) contracted arteries which were without tone or spontaneous activity and sometimes induced rhythmic contractile activity. If spontaneous rhythmic activity was present it was enhanced by histamine. The contractile effects of histamine were inhibited by mepyramine but not by cimetidine. Arteries which were contracted by depolarization responded with relaxation to histamine concentrations lower than those required to evoke a contraction; arteries from younger hearts were more sensitive than those from older hearts. Mepyramine potentiated the maximal relaxant effect of histamine in arteries from hearts of all ages but cimetidine had very little effect. In the presence of mepyramine, cimetidine antagonized the relaxant effect of histamine, shifting the concentration-effect curve to the right. It is concluded that human coronary arteries contain both H1- and H2-type receptors, the H1-receptors mediating contraction. The relaxant effects of histamine can only be inhibited by a combination of both H1- and H2-receptor antagonists.

Adolescent↗

Effects of yohimbine, rauwolscine and corynanthine on contractions and calcium fluxes induced by depolarization and prostaglandin F2 alpha in rat aorta.

The effects of the selective alpha 2-adrenoceptor antagonists yohimbine and its stereo-isomer rauwolscine and the selective alpha 1-adrenoceptor antagonist corynanthine (a third yohimbine stereoisomer) on contractions induced in rat aorta by depolarization and prostaglandin F2 alpha (PGF2 alpha) have been compared. In calcium-free solution, depolarization with 100 mM K+ failed to produce a contraction of rat aorta but PGF2 alpha (3 microM) stimulated a contraction equal to about 23% of maximal elicited in normal physiological solution. Yohimbine had no significant effect on depolarization-induced contractions except at concentrations greater than 30 microM. Rauwolscine and corynanthine (1 to 100 microM) depressed depolarization-induced contractions in a concentration-dependent manner, but the characteristics of inhibition were not identical. Contractions induced by PGF2 alpha (3 microM) were depressed in a concentration-dependent manner by rauwolscine (3 to 100 microM) but were unaffected by yohimbine or corynanthine. Depolarization-stimulated 45Ca influx was depressed by rauwolscine and corynanthine to about the same extent as were the contractions; while rauwolscine (100 microM) completely inhibited PGF2 alpha-stimulated 45Ca influx, it also depressed part of the PGF2 alpha-stimulated contraction dependent on intracellular calcium. Rauwolscine (100 microM) partly inhibited PGF2 alpha-stimulated release of 45Ca from aortic smooth muscle in calcium-free solution. It is concluded that the yohimbine structure possesses a calcium entry blocking action as well as a depressant action on contractions not dependent on calcium entry. The predominant effect depends on the structural configuration and the nature of the stimulating agent.

Animals↗

p-Azidophenylglyoxal-epidermal growth factor: a photoactivatable affinity crosslinking reagent.

A photoaffinity derivative of highly purified 125I-labelled epidermal growth factor (125-I-EGF) has been synthesized. The heterobifunctional crosslinking reagent p-azidophenylglyoxal (PAPG) was bound to arginine residues in 125I-EGF. PAPG-125 I-EGF bound to EGF receptors on rat fibroblasts and human A431 epidermoid carcinoma cells in culture. An apparent decreased affinity of PAPG-125I-EGF for the EGF receptor is in accord with at least one arginine being at or near the EGF receptor binding site. The PAPG-125I-EGF:EGF receptor complexes on rat cells were internalized to the same extent as control EGF:receptor complexes. A431 cells treated with PAPG-125I-EGF were irradiated with ultraviolet light and the labelled proteins were analyzed by SDS-polyacrylamide gel electrophoresis. The 3 major labelled proteins had apparent molecular weights ranging from 75,000 to 200,000. Only the labelling of the 200,000-Mr protein was prevented by the addition of excess unlabelled EGF with the PAPG-125I-EGF. This molecular weight is in agreement with the reported size of the EGF receptor plus EGF. A protein with apparent molecular weight of 100,000 was labelled by 125I-EGF by an unknown mechanism which was dependent on the dose of UV light and blocked by the addition of excess unlabelled EGF.

Aldehydes↗