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N Caldwell

Publications and source records attributed to N Caldwell.

At least 19 recordsLinked to original sources
PubMed2000

Spectral Variations in Early-Type Galaxies as a Function of Mass.

We report on the strengths of three spectral indicators-Mg(2), Hbeta, and Hn/Fe-in the integrated light of a sample of 100 field and cluster E/S0 galaxies. The measured indices are sensitive to age and/or metallicity variations within the galaxy sample. Using linear regression analysis for data with nonuniform errors, we determine the intrinsic scatter present among the spectral indices of our galaxy sample as a function of internal velocity dispersion. Our analysis demonstrates that there is significantly more intrinsic scatter in the two Balmer line indices than in the Mg(2) index, indicating that the Balmer indices provide more dynamic range in determining the age of a stellar population than does the Mg(2) index. Furthermore, the scatter is much larger for the low velocity dispersion galaxies, indicating that star formation has occurred more recently in the lower mass galaxies.

Journal Article↗
PubMed1991

Evaluation of calcium magnesium acetate and road salt for contact hypersensitivity potential and dermal irritancy in humans.

Calcium magnesium acetate (CMA) and road salt are both de-icing agents to which workers may be dermally exposed. A commercial formulation of CMA (Chevron Ice-B-Gon Deicer) and road salt were tested in a human repeat insult patch test to evaluate the contact hypersensitivity potential of these materials and to evaluate irritation following single or multiple applications. 72 of the initial 82 panelists completed the study. CMA and road salt (each at 10% and 30% w/w in distilled water; 0.3 ml) were administered under occlusive patches on the forearm for 14 h 3 x per week for 3 weeks. The panelists were challenged 2 weeks later; 2 panelists who had mild reactions were subsequently rechallenged 6 weeks later. Neither CMA nor road salt produced contact hypersensitivity in any panelists. Following the first application, moderate acute irritation was observed only at 1 skin site exposed to 30% road salt. Repeated exposure to CMA or road salt produced mild to moderate irritation. The highest incidence of moderate irritation was observed with 30% road salt. Thus, neither material is expected to cause significant dermal effects in exposed workers. CMA is expected to cause dermal irritation equivalent to or less than that caused by road salt.

Acetates↗
PubMed1991

Vasopressin antidiuretic agonist and antagonist activity in dogs: structural and stereochemical relationship between bridge and carboxyl terminus.

A series of vasopressin analogs with various amino acid tail modifications were tested for antidiuretic agonist and antagonist (water diuretic) activity in the water-loaded indomethacin-treated and hydropenic dogs, respectively. Changing the carboxy terminus from Cys6-Pro7-Arg8-NH2 in SK&F 101926 to Cys6-Arg7-NH2 or to D-Cys6-Pro7-Arg8-NH2 or to D- or L-Cys6-Arg7-D-Arg8-NH2 reduced antidiuretic agonist and increased water diuretic activity. Replacement of the sulfur atoms in the cysteine residues with methylene groups further reduced the antidiuretic agonist activity of all carboxy terminus-modified compounds which possessed full agonist activity. It also increased the water diuretic activity of those disulfide analogs with both weak agonist and antagonist activity. These results indicate that alterations in the geometry of the hexapeptide ring and in the stereochemical relationship between the ring and the carboxy terminus of the molecule substantially modify the in vivo agonist and antagonist activity of vasopressin analogs.

Amino Acid Sequence↗
PubMed1990

Physiological regulation of the renal vasopressin receptor-effector pathway in dogs.

Physiological regulation of receptor-effector pathways is recognized as a significant factor determining target organ selectivity and sensitivity in several hormonal systems. Whether or not physiological regulation of the renal vasopressin (V2) receptor-effector pathway participates in the control of body fluid homeostasis is unknown. We evaluated four states likely to be associated with altered sensitivities of the renal V2 receptor-effector pathway as follows: dehydration (18-h hydropenia), volume expansion, exogenous arginine vasopressin (AVP) infusion (10 ng/kg + 0.25 ng.kg-1.h-1), and cyclooxygenase blockade (indomethacin, 2 mg/kg + 2 mg.kg-1.h-1) for effects on the antidiuretic efficacies and potencies of putative V2-receptor antagonists in conscious dogs. The antidiuretic efficacies of desGly9[Pmp1-D-Tyr(Et)2Val4]AVP [Smith Kline & French (SK&F) 101926; 0.01-1,000 micrograms/kg] ranged from that of a full agonist to that of an antagonist, depending on the physiological state studied. The vasopressin antagonist potency of SK&F 101926 was increased 150-fold in association with extracellular volume expansion and decreased by blockade of renal cyclooxygenase activity. This spectrum of activities is that anticipated for a partial agonist under conditions where receptor number and/or sensitivity of receptor-effector coupling is increased or decreased, respectively. Thus volume expansion and increased circulating vasopressin concentration are associated with effective decreases, whereas hydropenia and cyclooxygenase blockade are associated with effective increases in sensitivity of the renal V2 receptor-effector pathway in the dog kidney. We conclude that the V2 receptor-effector pathway is a site of integration of physiological mechanisms participating in the control of body fluid homeostasis in conscious dogs.

Animals↗
PubMed1989

A minor modification of residue 1 in potent vasopressin antagonists dramatically reduces agonist activity.

[1-(beta,beta-Pentamethylene-beta-mercaptopropionic acid),2-(O-ethyl)-D- tyrosine,4-valine,9-desglycine]arginine-vasopressin (SK&F 101926, 1), a potent in vivo and in vitro vasopressin V2 receptor antagonist, was recently tested in human volunteers and shown to be a full antidiuretic agonist. A new animal model for vasopressin activity has been developed in dogs that duplicates the clinical agonist findings exhibited with SK&F 101926. In this model we have discovered that substitution of a cis-4'-methyl group on the Pmp moiety at residue 1 of vasopressin antagonists results in substantially reduced agonist activity compared to the unsubstituted molecule (SK&F 101926). The corresponding analogue with a trans-4'-methyl group exhibits more agonist activity than the cis molecule. These findings can be explained by viewing the biological activities of compounds such as 1 as the interaction of the vasopressin receptor with a number of discrete molecular entities, conformers of 1, which present different pharmacophores. Models have been developed to assist in the understanding of these results.

Adenylyl Cyclase Inhibitors↗
PubMed1989

Cyclooxygenase inhibition unmasks the full antidiuretic agonist activity of the vasopressin antagonist, SK&F 101926, in dogs.

The vasopressin (AVP) antagonist, SK&F 101926 (beta-mercapto-beta beta-cyclopentamethylene propionic acid1, D-Tyr(Et)2, Phe3, Val4, Asn5, Cys6, Pro7, Arg8-NH2), is an antidiuretic antagonist in rats and squirrel monkeys in vivo. In rat, dog, pig, squirrel monkey and human in vitro studies, SK&F 101926 is an AVP antagonist with no discernable agonist activity. Not predicted by these studies was the discovery that SK&F 101926 is an antidiuretic agonist in humans. The purpose of these studies was to show that indomethacin, which potentiates the antidiuretic activity of AVP in hydrated dogs, also potentiates the antidiuretic agonist activity of SK&F 101926, and to determine what structural modifications of this AVP antagonist would confer diminished agonist activity. Treatment of dogs with i.v. indomethacin (2 mg/kg bolus + 3 mg/kg/hr infusion, a dose which inhibited 80-90% of the urinary prostaglandin E2 excretion) unmasked the full antidiuretic activity of SK&F 101926. SK&F 104146 (Arg7-D-Arg8-NH2 peptide tail modification of SK&F 101926) in the presence of indomethacin caused a partial antidiuretic response. Replacement of the 1 to 6 disulfide bridge of SK&F 104146 with methylene groups to form a "dicarba bridge" resulted in SK&F 105494, a compound lacking antidiuretic agonist activity. Using the indomethacin-treated dog model, we have unmasked the full antidiuretic agonist activity of SK&F 101926 in nonhumans. In addition, both SK&F 104146 and 105494 blocked the antidiuretic agonist activity of SK&F 101926, suggesting that the agonist effect seen in the presence of indomethacin treatment is receptor mediated.

Animals↗
PubMed1988

SK&F 105494: a potent antidiuretic hormone antagonist devoid of partial agonist activity in dogs.

Previous studies from our laboratory have shown that in vivo cyclooxygenase blockade in dogs unmasks the antidiuretic agonist activity associated with the vasopressin antagonist, SK&F 101926, and have revealed two new vasopressin analogs, SK&F 104146 and 105494, with greatly reduced antidiuretic agonist activity. The purpose of the present study was to characterize SK&F 104146 and SK&F 105494 for water diuretic activity (aquaretic activity) in hydropenic dogs and for antagonism of vasopressin-stimulated antidiuresis in hydrated dogs. The vasopressin receptor affinity and inhibition of vasopressin-stimulated adenylate cyclase activity in renal membranes were also studied. When administered to hydropenic dogs, SK&F 101926 (3 or 30 micrograms/kg) did not cause a water diuresis. Substitution of the dipeptide tail of SK&F 101926 with Arg7D-Arg8NH2 (SK&F 104146; 30 micrograms/kg) was associated with a reduction of urine osmolality from 1876 +/- 182 to 349 +/- 94 mOsm/kg of H2O, and an increase in free water clearance (from -0.32 +/- 0.09 to 0.06 +/- 0.09 ml/min). Replacement of the 1 to 6 disulfide bridge of SK&F 104146 with a 1 to 6 dicarba bridge (SK&F 105494; 3 micrograms/kg) was associated with a further reduction of urine osmolality (1709 +/- 281 to 210 +/- 79 mOsm/kg of H2O) and a net positive free water clearance (from -0.56 +/- 0.02 to 0.6 +/- 0.35 ml/min). In water diuretic dogs, SK&F 104146 and 105494 shifted the vasopressin dose-response for antidiuresis to the right. SK&F 105494 appeared to be 3 times more potent than SK&F 104146.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The selective effects of indomethacin on contractile responses of the isolated rat uterus.

These studies were initiated to examine the effects of indomethacin on uterine contractile responses to oxytocin, carbachol, bradykinin, angiotension II and isoproterenol. Isolated uterine horns used in this study were removed from immature (21 days old) ovariectomized Sprague-Dawley rats (40-50 gm). Pre-treatment of uterine horns with indomethacin (10(-3) M) for periods of 15,30,60,90, and 180 seconds resulted in maximal inhibition of oxytocin-induced contractions by 15 seconds. In an indomethacin dose-response study, oxytocin-induced contractions were completely eliminated by a dose of indomethacin of 10(-3) M. Utilizing doses of indomethacin (3.5 X 10(-4) and 5.0 X 10(-4) M) that significantly reduced oxytocin-induced contractions by 48 and 77% respectively, contractile responses induced by carbachol (10(-6) M), bradykinin (10(-6) M), and angiotension II (4 X 10(-11) M) were not significantly reduced. Relaxation of uterine smooth muscle by isoproterenol (10(-5) M) in the presence of carbachol (10(-5) M) was not altered by indomethacin pretreatment. Data from this study demonstrate that indomethacin selectively inhibits oxytocin-induced uterine contractions in the immature rat.

Angiotensin II↗
PubMed1978

Safety.

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Accident Prevention↗
PubMedDate not supplied

Clinical use of etomidate for anesthesia induction: a preliminary report.

Etomidate (0.3 mg/kg) and thiopental (4 mg/kg) were administered IV for induction of general anesthesia, comparing heart rate, blood pressure, respiration, and side effects. No significant difference between the drugs was found in the circulatory parameters, but respiration was more depressed by thiopental. A high incidence of the side effects of myoclonia and pain on injection was seen with etomidate. The incidence of side effects was not affected by speed of injection or type of premedication. Mechanisms to reduce the incidence of side effects are needed for etomidate to become a useful induction agent.

Adult↗
PubMedDate not supplied

Lorazepam premedication: lack of recall and relief of anxiety.

Premedication with lorazepam (4 mg), diazepam (10 mg), and a placebo was compared in a randomized, double-blind study of 95 adult surgical patients. Comparisons were made of recall of a memory card and events of the operative day, relief of anxiety, degree of somnolence, effects on blood pressure and heart rate, and incidence of side effects. Lorazepam produced a significant lack of recall (antegrade amnesia) compared to the other agents. Lorazepam produced a greater antianxiety effect than placebo and a greater degree of somnolence than diazepam or placebo. Since no adverse effects on blood pressure or heart rate occurred, lorazepam appears to show promise as a premedicant.

Adult↗