Detection of angiographically silent coronary atherosclerosis by intracoronary ultrasonography.
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Aged↗
Biomedical subjects
J K Harrison
Publications and source records attributed to J K Harrison.
Molecular characterization of alpha 1- and alpha 2-adrenoceptors.
Three 'alpha 1-adrenoceptors' and three 'alpha 2-adrenoceptors' have now been cloned. How closely do these receptors match the native receptors that have been identified pharmacologically? What are the properties of these receptors, and how do they relate to other members of the cationic amine receptor family? Kevin Lynch and his colleagues discuss these questions in this review.
Amino Acid Sequence↗
Orchestrating social change: an imperative in care of the chronically ill.
The ethical challenges of caring for the chronically ill are of increasing concern to nurses as they attempt to create humanitarian environments for long-term care. This article suggests two ethical perspectives to guide the agenda of the nursing profession to achieve social change in the care of the chronically ill and aging. First, a reemphasis on the public duties of the professions is recommended which extends beyond serving the interests of the nursing profession to recognizing the need to serve the common good. Second, the limitations of the autonomy paradigm are explored and the foundation for the development of a new moral paradigm is analyzed in terms of its' potential usefulness in addressing ethical problems of chronic illness. Several initiatives that nursing must undertake to facilitate the emergence of this paradigm are proposed.
Chronic Disease↗
Pharmacological characterization of rat alpha 2-adrenergic receptors.
We described previously the molecular characterization of a rat alpha 2B-adrenergic receptor and have shown also that the rat genome contains three closely related alpha 2-adrenergic receptor genes. To characterize the ligand-binding properties of these receptor gene products, we expressed the DNAs encoding these receptors individually in COS-1 cells and studied their binding to a wide variety of typical and atypical adrenergic ligands. The receptors displayed high affinity binding to the radioligand [3H] rauwolscine, with equilibrium dissociation constants ranging from 1.4 to 2.8 nM. Kinetic analysis of the binding of [3H]rauwolscine to membranes from transfected cells was in very good agreement with data obtained from saturation analysis. We examined the ability of a number of agents to compete for the binding of [3H]rauwolscine to the alpha 2-adrenergic receptor-transfected membranes. Whereas one of these receptors displayed a pharmacological profile typical of an alpha 2A-adrenergic receptor, the other two receptors showed similar pharmacological properties characteristic of an alpha 2B-adrenergic receptor. The two alpha 2B-like adrenergic receptors differed, however, in the ratios of Ki values for oxymetazoline and prazosin, as well as the Ki ratio of prazosin and yohimbine. In addition, the two alpha 2B-like adrenergic receptors had a 9-fold difference in affinity for chlorpromazine. The pharmacological characterization of the three rat alpha 2-adrenergic receptor gene products is consistent with the known pharmacology of alpha 2-adrenergic receptors, as documented using tissues and cell lines.
Animals↗
Left ventricular performance and clinical outcome after repeat balloon aortic valvuloplasty.
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Aortic Valve Stenosis↗
Balloon angioplasty of coarctation of the aorta evaluated with intravascular ultrasound imaging.
Intravascular ultrasound images were employed to evaluate aortic coarctation before and after balloon angioplasty. Measurements obtained with use of an ultrasound imaging catheter correlated well with measurements made with digital aortography, both in the area of coarctation and in areas proximal and distal to it. The intravascular ultrasound images dramatically revealed dissection of the aortic wall and an intimal flap that was not appreciated on cineaortography or digital subtraction angiography. Intravascular ultrasound imaging may yield important morphologic information unavailable by other imaging techniques. Such information may allow more precise definition of the results of intravascular procedures and improve understanding of lesion characteristics predictive of a successful outcome.
Adult↗
Failure of balloon aortic valvuloplasty to result in sustained clinical improvement in patients with depressed left ventricular function.
Although balloon aortic valvuloplasty usually results in acute hemodynamic improvement, recurrent symptoms often occur within several months. The current study was designed to determine whether clinical characteristics, including invasive hemodynamic parameters of left ventricular (LV) performance, are predictive of short-term patient outcome. Eighty-one consecutive patients were prospectively enrolled in the study protocol. High-fidelity dual sensor micromanometer catheters, digital ventriculography and aortography and Fick cardiac output were measured before and immediately after balloon aortic valvuloplasty. Stroke work was defined from pressure-volume loops. The acute hemodynamic results obtained in patients with overall improved symptoms were compared to those with recurrent symptoms at 3 months. Fifty-three patients (65%) were improved at 3-month evaluation (group 1), whereas 28 patients (35%) had either returned to symptoms at baseline (17), had undergone aortic valve replacement (3) or had cardiac death (8). Compared to patients with improved symptoms, patients with recurrent symptoms demonstrated a lower cardiac output, higher LV end-systolic volume, decreased LV ejection fraction, diminished LV stroke work and decreased LV peak positive dP/dt. The final aortic valve area and change in aortic valve area did not predict which patients would develop recurrent symptoms. Stepwise logistic regression revealed that LV ejection fraction was the only independent predictor of overall status at 3 months (p = 0.002). Eighty-four percent of patients with an ejection fraction greater than 45% were improved. In the group with an ejection fraction greater than 45%, less than half of the patients demonstrated improved symptoms at short-term followup. Parameters of LV performance can accurately predict short-term patient outcome after balloon aortic valvuloplasty.
Aged↗
A rapid, effective technique for retrograde crossing of valvular aortic stenosis using standard coronary catheters.
Retrograde crossing of valvular aortic stenosis can be challenging even to experienced angiographers. In 446 of 447 consecutive patients with aortic stenosis catheterized during the past 3 years, a technique using a standard Judkins right coronary catheter and a floppy straight tipped guide wire was successful in rapidly and efficiently crossing these pathologically distorted valves in retrograde fashion. Once the valve was crossed, the coronary catheter was replaced with a pigtail catheter for pressure and ventriculography. The majority of these valves required less than 2 min to cross using this technique. This method is valuable in limiting the time required for catheterization, thus helping to reduce procedure related morbidity in these oftimes critically ill patients.
Aged↗
Percutaneous balloon pulmonic valvuloplasty following treated endocarditis in a patient with congenital pulmonary valve stenosis.
A 36-year-old woman with congenital pulmonary valve stenosis developed the rare complication of endocarditis of the valve. After successful sterilization of the valve, the patient underwent percutaneous balloon pulmonic valvuloplasty at a later date. The procedure successfully reduced the peak pulmonary valve gradient from 94 to 45 mm Hg. Percutaneous balloon valvuloplasty is the procedure of choice for treatment of congenital pulmonary valvular stenosis, even in the unusual patient who has healed endocarditis of the pulmonary valve.
Adult↗
Intravascular ultrasonography versus digital subtraction angiography: a human in vivo comparison of vessel size and morphology.
The accuracy of catheter-based intravascular ultrasonography to define luminal size in humans in vivo and its sensitivity to describe lesion morphology have not been previously reported. Vessel diameter, cross-sectional area and lesion characteristics assessed by digital subtraction angiography and intravascular ultrasonography (20 MHz) were compared in 86 human arterial segments. The same arterial segments were imaged and analyzed by digital subtraction angiography and intravascular ultrasonography at 49 femoral, 3 renal, 5 iliac, 7 pulmonary and 22 aortic sites. Digital subtraction angiographic diameter and area were determined geometrically by an automated algorithm. Intravascular ultrasonographic diameter and area were determined by planimetry. Linear correlation for diameter by the two techniques was 0.97, standard error of the estimate (SEE) = 1.83 mm, and for cross-sectional area it was 0.95, SEE = 0.65 cm2. Intravascular ultrasonography identified 24 sites in which plaque was present; 11 (46%) of these segments appeared normal by digital subtraction angiography. Conversely, digital subtraction angiography demonstrated irregularities in 18 segments of which 5 (28%) appeared normal by intravascular ultrasonography. These data indicate an excellent correlation between intravascular ultrasonography and digital subtraction angiography for in vivo assessment of human arterial dimensions in normal and minimally diseased segments. However, intravascular ultrasonography is more likely to identify atherosclerotic plaque that may be angiographically "silent."
Angiography, Digital Subtraction↗
Serial left ventricular performance evaluated by cardiac catheterization before, immediately after and at 6 months after balloon aortic valvuloplasty.
Although impaired ventricular function has been shown to improve after aortic valve replacement, there are few data on hemodynamic changes after balloon aortic valvuloplasty based on follow-up catheterization. Of 71 patients surviving 6 months after balloon aortic valvuloplasty, 41 agreed to late recatheterization. All patients had pre- and postvalvuloplasty and 6 month catheterization data measured with high fidelity micromanometer pressure recordings and simultaneous digital subtraction left ventriculography. The hemodynamic result immediately after valvuloplasty included a reduction in the aortic valve gradient and a moderate increase in aortic valve area (0.51 +/- 0.14 to 0.81 +/- 0.19 cm2, p less than 0.0001). Ejection fraction increased slightly (52 +/- 18 to 55 +/- 17%, p less than 0.0001) despite a decrease in peak positive rate of rise of left ventricular pressure (dP/dt 1,650 +/- 460 to 1,500 +/- 490 mm Hg/s, p less than 0.05). There was also a decrease in left ventricular afterload and a small decrease in preload. At 6 month recatheterization, the mean aortic valve gradient and area were similar to baseline values, with 31 (76%) of 41 patients demonstrating valvular restenosis. At 6 months many left ventricular hemodynamic variables, including peak positive dP/dt and stroke work, also resembled prevalvuloplasty values. However, left ventricular end-diastolic volume was reduced (111 +/- 40 ml at 6 months versus 136 +/- 52 ml before valvuloplasty, p less than 0.01). The mean left ventricular ejection fraction was unchanged from prevalvuloplasty values in the study group of 41 patients, but was significantly improved in 9 of 15 patients with a baseline ejection fraction less than 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Molecular characterization of a rat alpha 2B-adrenergic receptor.
Alpha 2-adrenergic receptors comprise a heterogeneous population based on pharmacologic and molecular evidence. We have isolated a cDNA clone (pRNG alpha 2) encoding a rat alpha 2-adrenergic receptor. A rat kidney cDNA library was screened with an oligonucleotide complementary to a highly conserved region found in all biogenic amine receptors described to date. The deduced amino acid sequence displays many features of guanyl nucleotide-binding protein-coupled receptors except it does not have a consensus N-linked glycosylation site near the amino terminus. Membranes prepared from COS cells transfected with pRNG alpha 2 DNA display high affinity and saturable binding to [3H]rauwolscine (Kd = 2 nM). Competition curve data analysis shows that RNG alpha 2 protein binds to a variety of adrenergic drugs with the following rank order of potency: yohimbine greater than or equal to chlorpromazine greater than or equal to prazosin greater than or equal to clonidine greater than norepinephrine greater than or equal to oxymetazoline. RNG alpha 2 RNA accumulates in both rat kidney and neonatal rat lung (predominant species is 4000 nucleotides). When a cysteine residue (Cys-169) that is conserved among all members of the seven-transmembrane-region superfamily is changed to phenylalanine, the RNG alpha 2 protein fails to bind [3H]rauwolscine after expression in COS cells. We conclude that pRNG alpha 2 likely represents a cDNA for a rat alpha 2B-adrenergic receptor.
Animals↗
Regulation of calmodulin-sensitive adenylate cyclase by the stimulatory G-protein, Gs.
Studies in bovine and rat brain membranes have suggested that calmodulin can potentiate neurotransmitter- and GTP-stimulated adenylate cyclase activities. To examine whether calmodulin and the stimulatory G-protein, Gs, are potentiative at a calmodulin-sensitive adenylate cyclase, Gs was purified from rabbit liver and reconstituted with a partially purified calmodulin-sensitive adenylate cyclase from bovine brain. Activated Gs (G*s) stimulated basal adenylate cyclase activity and enhanced the stimulation by calmodulin. The potentiation of the calmodulin-stimulated adenylate cyclase activity was dose-dependent with respect to G*s concentration. At the highest concentration of G*s tested (3 nM), a 2-fold enhancement of the calmodulin-stimulated adenylate cyclase activity was observed at all concentrations of calmodulin. The synergistic activation of adenylate cyclase by calmodulin and Gs was dependent on the presence of Ca2+ and occurred at physiologically relevant Ca2+ concentrations. The potentiation was not observed when either a nonactivated Gs or a mixture of activated Gi/Go was used. G*s was not able to stimulate or potentiate a calmodulin-stimulated adenylate cyclase purified from membranes pretreated with the nonhydrolyzable GTP analog, guanyl-5'-yl beta,gamma-imidodiphosphate. Photochemical cross-linking of 125I-calmodulin-diazopyruvamide to proteins having an Mr corresponding to the known Mr of adenylate cyclase was not enhanced by G*s. The results demonstrate that the guanyl nucleotide-dependent enhancement of calmodulin-stimulated adenylate cyclase activity is mediated by G*s and suggest that G*s modulates the enzymatic turnover of the calmodulin-stimulated activity.
Adenylyl Cyclases↗
Development of a novel photoreactive calmodulin derivative: cross-linking of purified adenylate cyclase from bovine brain.
A novel photoreactive calmodulin (CaM) derivative was developed and used to label the purified CaM-sensitive adenylate cyclase from bovine cortex. 125I-CaM was conjugated with the heterobifunctional cross-linking agent p-nitrophenyl 3-diazopyruvate (DAPpNP). Spectral data indicated that diazopyruvoyl (DAP) groups were incorporated into the CaM molecule. Iodo-CaM-DAPs behaved like native CaM with respect to (1) Ca2+-dependent enhanced mobility on sodium dodecyl sulfate-polyacrylamide gels and (2) Ca2+-dependent stimulation of adenylate cyclase activity. 125I-CaM-DAP photochemically cross-linked to CaM-binding proteins in a manner that was both Ca2+ dependent and CaM specific. Photolysis of forskolin-agarose-purified adenylate cyclase from bovine cortex with 125I-CaM-DAP produced a single cross-linked product which migrates on sodium dodecyl sulfate-polyacrylamide gels with an apparent molecular weight of approximately 140,000.
Adenylyl Cyclases↗
Platypnea-orthodeoxia and progressive autonomic failure.
Platypnea-orthodeoxia has been described in patients with pulmonary shunts, intracardiac shunts, and severe lung disease. We report a case of platypnea-orthodeoxia in a patient with minimal obstructive lung disease and progressive autonomic failure. We have shown our patient's symptoms to be the result of an orthostatic increase in ventilation-perfusion mismatching and to be corrected with fluid challenge.
Autonomic Nervous System Diseases↗
On the active site of liver acetyl-CoA. Arylamine N-acetyltransferase from rapid acetylator rabbits (III/J).
A covalent, catalytic intermediate of cytosolic liver acetyl coenzyme A: arylamine N-acetyltransferase (EC 2.3.1.5) from rapid acetylator rabbits (III/J) was isolated and chemically characterized. The active site was further studied using two covalent inhibitors, [2-3H]iodoacetic acid and bromoacetanilide. Inhibition experiments with [2-3H]iodoacetic acid at pH 6.9 showed that the incorporation of 0.7 mol of [2-3H]iodoacetic acid/mol of N-acetyltransferase led to rapid, irreversible loss of enzyme activity. Preincubation of the enzyme with acetyl coenzyme A (acetyl-CoA) completely protected against inactivation by [2-3H]iodoacetic acid. After incubating the N-acetyltransferase with [2-3H]acetyl-CoA in the absence of an acceptor amine, an acetyl-cysteinyl-enzyme intermediate was isolated and characterized. Preincubation of N-acetyltransferase with iodoacetic acid prevented the incorporation of the [2-3H]acetyl group into the enzyme. The product analog, bromoacetanilide, caused a rapid irreversible loss of N-acetyltransferase activity. The reaction was pseudo first-order and saturated at high bromoacetanilide concentrations (KI = 0.67 mM; k3 = 1 min-1). Preincubation of the enzyme with acetyl-CoA prevented inactivation by the inhibitor. The acceptor amine 4-ethylaniline did not prevent inhibition. Incorporation of the inhibitor was directly proportional to the loss of activity showing a 1:1 stoichiometry of enzyme to inhibitor. The target amino acid was identified as cysteine by amino acid analysis of inhibitor-treated enzyme.
Acetanilides↗
Differential regulation by calmodulin of basal, GTP-, and dopamine-stimulated adenylate cyclase activities in bovine striatum.
The concentration requirements of calmodulin in altering basal, GTP-, and dopamine-stimulated adenylate cyclase activities in an EGTA-washed particulate fraction from bovine striatum were examined. In the bovine striatal particulate fraction, calmodulin activated basal adenylate cyclase activity 3.5-fold, with an EC50 of 110 nM. Calmodulin also potentiated the activation of adenylate cyclase by GTP by decreasing the EC50 for GTP from 303 +/- 56 nM to 60 +/- 10 nM. Calmodulin did not alter the maximal response to GTP. The EC50 for calmodulin in potentiating the GTP response was only 11 nM as compared to 110 nM for activation of basal activity. Similarly, calmodulin increased the maximal stimulation of adenylate cyclase by dopamine by 50-60%. The EC50 for calmodulin in eliciting this response was 35 nM. These data demonstrate that calmodulin can both activate basal adenylate cyclase and potentiate adenylate cyclase activities that involve the activating GTP-binding protein, Ns. Mechanisms that involve potentiation of Ns-mediated effects are much more sensitive to calmodulin than is the activation of basal adenylate cyclase activity. Potentiation of GTP-stimulated adenylate cyclase activity by calmodulin was apparent at 3 and 5 mM MgCl2, but not at 1 or 10 mM MgCl2. These data further support a role for calmodulin in hormonal signalling and suggest that calmodulin can regulate cyclic AMP formation by more than one mechanism.
Adenylyl Cyclases↗
Pharmacokinetics of long acting oxytetracycline in the laboratory rat.
Pharmacokinetic parameters of a slow release form of oxytetracycline were determined in the rat. Triexponential pharmacokinetics were displayed after intravenous administration. The half-life of the distribution phase was 0.097 hours, the rapid elimination half-life was 3.74 hours and the slow elimination half-life was 27.26 hours. Subcutaneous and intramuscular injection resulted in a rapid elimination half-life of 6.09 and 6.02 hours, respectively. In comparison, a standard form of oxytetracycline given subcutaneously had a rapid elimination half-life of 4.22 hours. The slow release form of oxytetracycline has a half-life in the rat long enough to maintain serum levels greater than the minimum inhibitory concentration of Mycoplasma pulmonis with a dose interval of 72 hours.
Animals↗