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Biomedical subjects

A I Cohen

Publications and source records attributed to A I Cohen.

At least 19 recordsLinked to original sources
PubMed1996

Effect of feedback from peripheral movements on neuron activity in the aplysia abdominal ganglion.

We have made reasonably comprehensive measurements of action potential activity in the Aplysia californica abdominal ganglion to determine the amount of feedback the central nervous system (CNS) receives from a movement which it initiates. Voltage-sensitive dye measurements of action potential activity of cells in the ganglion were made during the gill-withdrawal reflex elicited by siphon stimulation. We compared recordings in two situations which differed dramatically in the amount the gill moved. In the control sea water, the gill withdrawal was normal; in low-Ca2+, high-Mg2+ sea water, the gill movement was blocked. Both the timing and the number of spikes of the individual neurons were similar in the two situations. Histograms of the summed spike activity versus time and histograms of the number of active neurons versus time in the two conditions were also similar. Finally, two numerical measures of trial-to-trial differences, a paired t-test and a measure we named fractional similarity, did not indicate larger differences between two trials in the different sea waters than two trials in the same sea water. Feedback from sensory neurons activated by the gill movement itself does not make a large contribution to the spike activity in the abdominal ganglion. Apparently the Aplysia CNS issues the command for the withdrawal and does not make adjustments for the magnitude of the actual withdrawal. It may not even receive the information necessary for such adjustments to be made. A second motivation for these experiments was to test whether removing the feedback might simplify the neuronal activity that occurs during the gill-withdrawal reflex. This did not occur.

Abdomen↗
PubMed1993

Steady state serum concentrations of pravastatin and digoxin when given in combination.

Pravastatin is an HMG CoA reductase inhibitor used in the treatment of hypercholesterolaemia. The steady state pharmacokinetics of pravastatin (20 mg) and digoxin (0.2 mg) were evaluated in 18 healthy male subjects following the administration of each drug alone or in combination for 9 days. Serum and urine were collected for up to 48 h after the ninth dose in this open, randomized 3-way crossover study. Digoxin concentrations were measured by radioimmunoassay, and pravastatin and its metabolites. SQ 31,906 and SQ 31,945 were measured by GC-MS. Digoxin and pravastatin pharmacokinetics were unchanged following combined administration. Combination therapy with pravastatin and digoxin is unlikely to expose patients to additional risk compared with pravastatin alone.

Adult↗
PubMed1992

Photoreceptors of mouse retinas possess D4 receptors coupled to adenylate cyclase.

In the mouse, the light-sensitive pool of cAMP can be eliminated in the dark by application of the dopamine D2-like receptor agonists LY 171555 (quinpirole), (+)-N0437 (2-[N-(n-propyl)-N-2-(thienylethylamino)-5-hydroxytetralin]) , or (+)-3-PPP [3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride]. The rank-order affinity of the ability of the D2-like antagonists to block the action of LY 171555 matched that of the rat D4 receptor. Reverse transcription of retina mRNA followed by DNA amplification using D4-specific nucleotides demonstrates the presence of D4 mRNA in retina. In situ hybridization studies using D4-specific digoxygenin-labeled oligonucleotides or 35S-labeled UTP RNA probes demonstrate the presence of D4 mRNA in the photoreceptor cell layer and in the inner nuclear and ganglion cell layers. The modulation by D4 ligands of the dark level of light-sensitive cAMP in photoreceptors demonstrates the physiological coupling of the D4 receptor subtype.

Adenylyl Cyclases↗
PubMed1992

Determination of SQ 33,600, a phosphinic acid containing HMG CoA reductase inhibitor, in human serum by high-performance liquid chromatography combined with ionspray mass spectrometry.

A method for the determination of SQ 33,600 in human serum is presented. This compound, which contains both carboxylic and phosphinic acid functional groups, is an HMG CoA reductase inhibitor currently under clinical investigation at the Bristol-Myers Squibb Pharmaceutical Research Institute. Human serum extracts prepared using solid-phase techniques were analyzed by combining high-performance liquid chromatography and atmospheric pressure ionization mass spectrometry. Under the conditions of the analysis, SQ 33,600 and its fluorinated analog, SQ 33,547, used as the internal standard, existed as anions in solution and could be sampled directly using the ionspray technique. The method utilized a simple isocratic mobile-phase system. No sample derivatization was required for these polar molecules. The retention time of the analytes was 3.5 min with a total analysis time of 5 min. The limit of detection was 0.5 ng ml-1 serum with a minimum quantifiable limit of 2.0 ng ml-1. The method was linear to at least 400 ng ml-1.

Chromatography, High Pressure Liquid↗
PubMed1991

High-performance liquid chromatographic determination of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil and its metabolite (E)-5-(2-bromovinyl)uracil in serum.

A high-performance liquid chromatographic method was developed to assay 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil and its metabolite (E)-5-(2-bromovinyl)uracil in serum. The chloro analogue of the parent drug is used as internal standard. Human serum samples were assayed to establish the pharmacokinetic parameters. Acetonitrile, used as a protein precipitant, was evaporated to dryness and the residue, containing the analytes and internal reference, was dissolved in mobile phase prior to chromatographic analysis. The minimum quantifiable level was 0.02 micrograms of each analyte per ml of serum.

Antiviral Agents↗
PubMed1990

Dopamine and its agonists reduce a light-sensitive pool of cyclic AMP in mouse photoreceptors.

The exposure to bright light of dark-adapted (DKA) mouse retinas incubated in the dark (DI) in IBMX-containing medium causes a marked loss of cyclic AMP. This light response also occurs if the medium contains 10 mM aspartate or cobaltous ion, agents believed to confine the effects of light to photoreceptors. Thus, the action of light in the presence of either of these agents defines a light-sensitive pool of cyclic AMP in photoreceptors. This pool could also be reduced or eliminated in DKA-DI retinas by nanomolar to micromolar levels of dopamine (if the medium contained SCH23390, a potent antagonist of D1 receptors), thus indicating an agonistic action of dopamine at D2 receptors. The D2 agonists LY171555 (EC50 10 nM) or (+)-3-PPP also reduced the cyclic AMP level in the dark. Of the D2 antagonists tested, the butyrophenone spiperone (in the presence of the 5HT-2 blocker ketanserin) countered the action of the D2 agonists but substituted benzamides were ineffective. Consistently, the D2 agonists had no effect on cyclic AMP levels of mutant retinas lacking photoreceptors (rd/rd), but reduced cyclic AMP in DKA-DI glutamate-modified retinas which exhibit a major loss of inner retinal neurons without apparent loss of photoreceptors. The D1 antagonist SCH23390 only reduced cyclic AMP levels of DKA-DI retinas when cyclic AMP levels had been elevated by adding dopamine to the incubation medium.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Interphotoreceptor contacts at the inner segment level in primate retinas.

Just sclerad to the external limiting membrane of the retina of the monkey (M. fasciculata), short processes from some foveolal and foveal cone inner segments made dense contacts with each other and at the same level of peripheral human retina similar rod-cone and rod-rod contacts were observed.

Animals↗
PubMed1989

Body fluid analysis of a phosphonic acid angiotensin-converting enzyme inhibitor using high-performance liquid chromatography and post-column derivatization with o-phthalaldehyde.

A method is described for the extraction of a phosphonic acid angiotensin-converting enzyme inhibitor from either urine or plasma, and subsequent quantitation using high-performance liquid chromatographic (HPLC) analysis and post-column o-phthalaldehyde reagent derivatization. The compound cannot be quantitatively extracted from the body fluids, but use of a fluorinated internal standard allowed for the computation of accurate results. With the use of an internal standard, excellent precision, linearity, and recovery were obtained for analyte response in both urine and plasma. In urine a working range of 0.2-10 micrograms/ml was found, with a limit of detection of 0.1 micrograms/ml. For plasma the working range was found to be 2-500 ng/ml, and the limit of detection was established as 1 ng/ml. Due to the non-polar character of the analyte at low pH values, it was possible to use novel extraction (solid-phase C8 column) and HPLC [poly(styrenedivinyl benzene) HPLC column] conditions to separate and quantitate the compound from plasma and urine.

Chemical Phenomena↗
PubMed1989

Determination of pravastatin sodium and its major metabolites in human serum/plasma by capillary gas chromatography/negative ion chemical ionization mass spectrometry.

A capillary gas chromatography/negative ion chemical ionization mass spectrometry method has been developed to measure pravastatin sodium, an anti-hypercholesterolemic agent, and two of its major metabolites in human serum. Injected on a capillary column, derivatized pravastatin sodium and the two, metabolites were detected at levels of 0.5 pg microliters-1 injected with a signal-to-noise ratio of 3 to 1. The limit of detection was 0.3 ng ml-1 serum of each compound with 95% confidence using a weighted linear regression analysis. Prior to analysis, samples were purified on 200 mg C18 solid-phase extraction columns and derivatized with pentafluorobenzyl bromide and N,O-bis-(trimethylsilyl)-trifluoroacetamide. An excess of pentafluorobenzyl bromide was removed by reaction with propionic acid.

Anticholesteremic Agents↗
PubMed1989

Determination of lovastatin acid in serum by gas chromatography/mass spectrometry.

The acid form of lovastatin, an HMG-CoA reductase inhibitor, was analyzed by gas chromatography/negative-ion chemical ionization mass spectrometry after derivatization with pentafluorobenzyl bromide and bis-(trimethylsilyl)trifluoroacetamide (BSTFA). Mass spectrometry of this derivative produced a dominant [M-181]- ion under chemical ionization conditions using ammonia as the reagent gas. The limit of detection was approximately 2 pg injected on column.

Gas Chromatography-Mass Spectrometry↗
PubMed1989

Transdiaphragmatic implantation of the automatic implantable cardioverter defibrillator.

A new surgical approach for implantation of the automatic implantable cardioverter defibrillator without thoracotomy was used in 12 patients, aged 46 to 72 years. Preimplantation arrhythmia was ventricular tachycardia in 7 patients and ventricular fibrillation in 5 patients. The mean ejection fraction was 19%. Six patients were at high risk for general anesthesia for a variety of medical problems, and 2 patients had had a previous cardiac operation. Epidural anesthesia was used in 8 patients without intubation. The surgical approach used a longitudinal epigastric extraperitoneal incision with access to the heart through an incision made in the central tendon of the diaphragm. Two patches and two epicardial sensing leads were placed in all patients. All patients but one could be defibrillated with 20 J or less. There was no operative mortality and minimal morbidity. There were two late deaths due to heart failure. Thus, the transdiaphragmatic approach provides an excellent exposure for automatic implantable cardioverter defibrillator implantation, avoids general anesthesia and thoracotomy, and can be used after a previous cardiac operation.

Aged↗
PubMed1989

Comparison of adenosine uptake and endogenous adenosine-containing cells in mammalian retina.

Autoradiographic techniques were used to label [3H]-adenosine and [3H]-cyclohexyladenosine accumulating cells in rabbit, mouse, and ground squirrel retinas. Immunohistochemical methods revealed the distribution of cells that stained for endogenous adenosine. Comparisons of these two markers revealed for all three species that the distribution of specific subpopulations of retinal cells that store or accumulate the purine nucleoside, adenosine, is similar. For all three species, cells localized in the ganglion cell layer accumulated adenosine and exhibited adenosine-like immunoreactivity (ALIR). A smaller proportion of cells localized in the inner nuclear layer were labeled for ALIR, while a larger proportion of cells in this layer accumulated adenosine. Subtle differences between species are presented. However, the general similarities of the distribution of these two putative purinergic markers supports the evidence that a discrete adenosinergic neurotransmitter/modulatory system is present in the retina.

Adenosine↗
PubMed1989

Adenosine: autoradiographic localization and electrophysiologic effects in the cat retina.

Autoradiography with 3H-adenosine was used to localize cells that accumulate adenosine in the cat retina. Electrophysiologic effects elicited by adenosine on DC-electroretinograms (ERG) and optic nerve responses (ONR) were studied in isolated, arterially perfused cat eyes. Subpopulations of cells localized in the ganglion cell layer and inner nuclear layer showed clear labeling for adenosine. This purine nucleoside enhanced the ERG b-wave and the standing potential; depressed the light peak; and markedly depressed the ONR, in which it reduced the amplitudes of the ON-, plateau-, and OFF-components. A vasodilatory action of adenosine was documented by an increase in perfusion flow rate. Our data suggest that adenosine in cat retina has complex modulatory effects, involving the retinal pigment epithelium, neuronal structures, blood vessels, and probably glial cells.

Adenosine↗
PubMed1988

Serial electrocardiographic changes in idiopathic dilated cardiomyopathy confirmed at necropsy.

Serial electrocardiographic changes in necropsy-proven idiopathic dilated cardiomyopathy are evaluated and a method of predicting heart weight using QRS amplitudes is described. In 34 patients with multiple electrocardiograms (mean 3/patient) progressive prolongation of PR interval (0.18 +/- 0.03 to 0.21 +/- 0.03, p less than 0.001) and QRS duration (0.10 +/- 0.02 to 0.13 +/- 0.03, p less than 0.0001) was noted. Progressive conduction abnormalities were common (82%). QTc interval and QRS- and T-wave axes did not change. In 50 patients with electrocardiograms within 60 days of death, total 12-lead QRS and V1 through V6 QRS amplitude correlated better with heart weight (r = 0.51, p less than 0.0001 and r = 0.55, p less than 0.0001) than the Estes-Romhilt score did. The mean total 12-lead QRS amplitude was 138 mm with a mean of 106 for V1 through V6. In 31 patients cardiac mass index was calculated and showed significant correlation with 12-lead and V1 through V6 QRS amplitudes (r = 0.68, p less than 0.0001 and r = 0.75, p less than 0.0001, respectively). The QRS amplitudes remained constant during the illness. By using total 12-lead QRS or frontal plane QRS amplitude, heart weight can be predicted as early as 2 years before death. Use of body surface area and QRS amplitude criteria increases the accuracy of heart weight prediction. Thus, progressive electrocardiographic changes are common in patients with idiopathic dilated cardiomyopathy and QRS amplitude criteria are more accurate in the prediction of left ventricular hypertrophy than standard criteria.

Adolescent↗
PubMed1988

Simultaneous determination of the prodrug zofenopril and its active drug in plasma by capillary gas chromatography-mass-selective detection.

After oral administration of zofenopril, the active sulfhydryl angiotensin-converting enzyme inhibitor is released. Zofenopril is currently under clinical investigation as an antihypertensive. Blood samples are reacted with N-ethylmaleimide, immediately after collection, processed into plasma and stored frozen for subsequent analysis. After addition of two internal reference standards, one each for the prodrug and the active compound, the plasma samples are purified by a combination of liquid-liquid and solid-phase extractions. The dried methylated extracts are reconstituted with tetramethylbenzene and chromatographed by automated splitless injection on a fused-silica capillary column, connected to a mass-selective detector. The analytes and the internal reference standards are chromatographically resolved and a common fragment ion is monitored for the analytes. A limit of quantitation of approximately 1 ng/ml of plasma is achieved.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

M-mode echocardiograms for determination of optimal left atrial timing in patients with dual chamber pacemakers.

To determine if the A wave of the mitral valve echocardiogram can be used as a marker for left atrial (LA) activity and assist in the programming of dual chamber pacemakers, 156 echocardiograms with the mitral A wave present were obtained from 23 patients with dual chamber pacemakers, all of whom had bipolar esophageal recordings of LA depolarization. Twelve of these patients also underwent hemodynamic study with cardiac function determined at 5 different pacemaker settings: ventricular demand pacing and dual chamber sequential pacing at 0 or 25, 150, 200 and 250 ms programming atrioventricular (AV) delay. The time delay from right atrial pacing artifact to onset and peak of mitral A wave was linearly related to the time from atrial pacing artifact to LA depolarization on the esophageal lead (p less than 0.001). As pacing mode changed from dual chamber sequential pacing (DVI) mode to atrial synchronous-ventricular pacing (VDD), the A wave came earlier relative to the ventricular pacing spike, linearly related to the LA to ventricular extension with mode change determined with the esophageal lead (r = 0.94, p less than 0.001). The time from atrial pacing to peak of A wave was shorter in patients whose optimal programmed AV delay was 150 ms compared with those whose optimal AV delay was 200 or 250 ms (p less than 0.02). At the optimal programmed delay for cardiac output, the peak of the A wave was an average of 13 +/- 36 ms after the ventricular pacing spike.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Light-induced losses and dark recovery rates of guanosine 3',5'-cyclic monophosphate in rod outer segments of intact amphibian photoreceptors.

We used an apparatus in which pieces of dark-adapted amphibian retinas (Rana pipiens, Bufo marinus) obtained under infrared illumination were exposed to precise intervals of 500-nm illuminations, and then frozen by contact of their outer segment surface with a liquid helium-cooled copper mirror. Sections of the frozen outer segment layer were obtained in a cryostat and then assayed for total extractable cyclic 3',5'-guanosine monophosphate (cGMP). Significant losses of cGMP with respect to the dark level were evident as early as 60 ms after light onset. With dim subsecond illuminations these losses were surprisingly large, which suggests a previously underestimated magnification in the cGMP cascade, or a transient substantial inhibition of guanylate cyclase activity in combination with increased cyclic GMP phosphodiesterase activity. Within the subsecond period, significant losses that were proportional to light intensity (2-log-unit range) and duration (60-550 ms) were generally not evident. However, losses significantly proportional to these factors became evident with durations of 1 s or longer. When pieces of retina were first illuminated (10 or 60 ms), then held in darkness for increasing periods before freezing, we observed a continuous loss of cGMP during the early postillumination dark period, followed by a recovery of the total cGMP level. The times for recovery to the preillumination level appear to be significantly longer than times reported for the recovery of the photoreceptor membrane potential after similar light exposures.

Animals↗