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Biomedical subjects

R A Johnson

Publications and source records attributed to R A Johnson.

At least 271 records · Page 15Linked to original sources
PubMed1980

Regulation of adenosine-sensitive adenylate cyclase from rat brain striatum.

An adenosine-sensitive adenylate cyclase has been characterized from rat brain striatum. In whole homogenates as well as in particulate fractions, N6-phenylisopropyl adenosine (PIA), 2-chloroadenosine, and adenosine N'-oxide were equipotent in stimulating adenylate cyclase. Although GTP inhibited basal as well as PIA-stimulated activity of whole homogenates, the enzyme showed an absolute dependency on GTP for stimulation by PIA, dopamine, epinephrine, and norepinephrine in a particulate fraction derived from discontinuous sucrose gradient centrifugation. Adenosine exerts two effects on this adenylate cyclase, stimulation at low concentrations and inhibition at high concentrations, suggesting the presence of two adenosine binding sites. The stimulation of adenylate cyclase by PIA was dependent on the concentration of Mg2+. The degree of stimulation by PIA was greater at a low concentration of MG2+, which suggests that stimulation by PIA was accompanied by increasing the apparent affinity for Mg2+. Activation of adenylate cyclase by PIA was blocked by theophylline or 3-isobutyl-1-methylxanthine (IBMX). The pH optimum for basal or (PIA + GTP)-stimulated activities was broad, with a peak between 8.5 and 9.5. In the presence of GTP, stimulation by an optimal concentration of PIA was additive, with maximal stimulation by the catecholamines. Phospholipase A2 treatment at a concentration of 1 U/ml for 5 min completely abolished the stimulatory effect of dopamine, whereas PIA-stimulated activity remained unaltered. These data suggest that rat brain striatum either has a single adenylate cyclase, which is stimulted by catecholamines and adenosine by distinct mechanisms, or has different cyclase populations, stimulated by either adenosine or catecholamines.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Sensory images in the absence of sight: blind versus sighted adolescents.

Sensory image scores that were obtained from 91 blind and 91 sighted adolescents aged 10 to 21 yr. were classified into seven sensory categories (visual, auditory, cutaneous, kinesthetic, gustatory, olfactory, symbolic, and organic sensations) according to a shortened form of the Betts Questionnaire Upon Mental Imagery. Blind adolescents were not restricted in the formation of visual images nor did the relative ordering of the sensory categories differ as a function of ability to see.

Adolescent↗
PubMed1980

Preparation of cyclic nucleotide antisera with thyroglobulin-cyclic nucleotide conjugates.

Antisera to cyclic AMP and cyclic GMP were obtained by immunizing rabbits with antigens prepared by conjugating the 2'0-succinyl derivative of the cyclic nucleotides to thyroglobulin. The cyclic nucleotide-thyroglobulin conjugates were injected intradermally into multiple sites on the backs of the animals. This immunization procedure resulted in the production of antiserum in four of five animals capable of binding at a final serum dilution of greater than 1:10,000, 20% of the corresponding iodinated cyclic nucleotide derivative added. The antisera were also highly specific. The antiserum for cyclic AMP had a 2500-fold or greater relative affinity for cyclic AMP than other nucleotides or nucleosides, while that for cyclic GMP had a 5000-fold or greater affinity for 2'0 acetylated nucleotides or nucleosides except for acetylated cyclic IMP. The obstacles to measuring cyclic nucleotides, particularly cyclic GMP, in tissues were also overcome by refining and simplifying the methods for iodination, purification and assay. Furthermore, a "disequilibrium" incubation was developed as an alternative to the acetylation method to increase the sensitivity of the radioimmunoassay. Thus, the levels of both cyclic GMP and cyclic AMP can be determined rapidly and easily in the same tissue sample.

Animals↗
PubMed1979

Regulation of platelet adenylate cyclase by adenosine.

The stimulatory and inhibitory effects of adenosine on the adenylate cyclases of human and pig platelets were studied. Stimulation occurred at lower concentrations than did inhibition, and the stimulatory effect was prevented by methylxanthines. Stimulation by adenosine was immediate in onset and was reversible, under conditions when cyclic AMP formation was linear with respect to time and protein concentration. The stimulatory and inhibitory effects could be distinguished further by the use of various analogues of adenosine and could be prevented by adenosine deaminase. The data suggest that both stimulation and inhibition were due to adenosine itself and not one of its degradation products and that in the platelet preparation, neither formation nor degradation of adenosine during the adenylate cyclase incubation appreciably influenced measured activity. Stimulation by adenosine was additive with the effects of GMP-P(NH)P, and alpha- or beta-adrenergic stimulation, but was abolished by prostaglandin E1 or by NaF. Prostaglandin E1 and NaF increased the sensitivity of adenylate cyclase to inhibition by adenosine. The data suggest that guanyl-5'-yl-(beta-gamma-imino)diphosphate and/or adrenergic stimulation and adenosine exert their effects on adenylate cyclase by distinct mechanisms, but that prostaglandin E1 or F- and adenosine increase enzyme activity by mechanisms which may involve common intermediates in the coupling to adenylate cyclase.

Adenosine↗
PubMed1979

The enzymatic preparation of [alpha-(32)P]nucleoside triphosphates, cyclic [32P] AMP, and cyclic [32P] GMP.

A method has been developed for the enzymatic preparation of alpha-(32)P-labeled ribo- and deoxyribonucleoside triphosphates, cyclic [(32)P]AMP, and cyclic [(32)P]GMP of high specific radioactivity and in high yield from (32)Pi. The method also enables the preparation of [gamma-(32)P]ATP, [gamma-(32)P]GTP, [gamma-(32)P]ITP, and [gamma-(32)P]-dATP of very high specific activity and in high yield. The preparation of the various [alpha-(32)P]nucleoside triphosphates relies on the phosphorylation of the respective 3'-nucleoside monophosphates with [gamma-(32)P]ATP by polynucleotide kinase and a subsequent nuclease reaction to form [5'-(32)P]nucleoside monophosphates. The [5'-(32)P]nucleoside monophosphates are then converted enzymatically to the respective triphosphates. All of the reactions leading to the formation of [alpha-(32)P]nucleoside triphosphates are carried out in the same reaction vessel, without intermediate purification steps, by the use of sequential reactions with the respective enzymes. Cyclic [(32)P]AMP and cyclic [(32)P]GMP are also prepared enzymatically from [alpha-(32)P]ATP or [alpha-(32)P]GTP by partially purified preparations of adenylate or guanylate cyclases. With the exception of the cyclases, all enzymes used are commerically available. The specific activity of (32)P-labeled ATP made by this method ranged from 200 to 1000 Ci/mmol for [alpha-(32)P]ATP and from 5800 to 6500 Ci/mmol for [gamma-(32)P]ATP. Minor modifications of the method should permit higher specific activities, especially for the [alpha-(32)P]nucleoside triphosphates. Methods for the use of the [alpha-(32)P]nucleoside phosphates are described for the study of adenylate and guanylate cyclases, cyclic AMP- and cyclic GMP phosphodiesterase, cyclic nucleotide binding proteins, and as precursors for the synthesis of other (32)P-labeled compounds of biological interest. Moreover, the [alpha-(32)P]nucleoside triphosphates prepared by this method should be very useful in studies on nucleic acid structure and metabolism and the [gamma-(32)P]nucleoside triphosphates should be useful in the study of phosphate transfer systems.

Adenosine Triphosphate↗
PubMed1979

Intramuscular inoculation of live respiratory syncytial virus induces immunity in cotton rats.

Intramuscular inoculation of infant or weanling cotton rats with 10(2.2) to 10(4) plaque-forming units of respiratory syncytial virus induced significant or complete resistance to infection in both the upper and lower portions of the respiratory tract. This resistance did not appear to be the result of in vitro neutralization of virus during homogenization of tissue. Virus was not recovered from the local site of inoculation after 5 min and was never detected in the respiratory tract of intramuscularly inoculated rats. Attempts to detect viral antigens at the site of inoculation by using indirect immunofluorescence were unsuccessful. However, inactivation of infectivity of three different strains of respiratory syncytial virus markedly reduced or completely ablated antigenicity and protective efficacy by the intramuscular route. This suggests that these viruses underwent limited replication, perhaps restricted to an abortive cycle, at the local site of inoculation. An immunosuppressive effect of passive maternally derived immunity was observed. Only 50% of weanling rats possessing passive maternal serum antibody were successfully immunized by intramuscular vaccination with live virus.

Animals↗
PubMed1979

Patterns of haemodynamic alteration during left ventricular ischaemia in man. Relation to angiographic extent of coronary artery disease.

Haemodynamic changes produced by rapid atrial pacing (60 patients, 52 of whom developed angina) or in association with spontaneous angina (32 patients) were measured in 92 patients with angiographic coronary artery disease. The extent of coronary artery disease was scored by the jeopardy score system (range 0 to 12). The haemodynamic changes induced by ischaemia occurred in 3 patterns: pattern I, no change in filling pressure or in mean systemic arterial pressure; pattern II, a rise in filling pressure and a rise in mean systemic arterial pressure; pattern III, a rise in filling pressure, but no significant change or a fall in mean systemic arterial pressure. In patients who had a pattern II or a pattern III response to ischaemia, the change in mean systemic arterial pressure was linearly related to the corresponding change in cardiac output. The likelihood of a patient showing a given pattern of ischaemia-induced haemodynamic change was related to the extent of coronary artery disease; of 22 patients with jeopardy scores of 2 or 4, 91% exhibited pattern I, 9% pattern II, and none pattern III; of 39 patients with jeopardy scores of 6 or 8, 40% exhibited pattern I, 22% pattern II, and 38% pattern III; of 31 patients with jeopardy scores of 10 or 12, 12% exhibited pattern I, 10% pattern II, and 78% pattern III (P less than 0.01). Among the 54 patients in whom serial cardiac output determinations were available, a decline of the left ventricular function curve during ischaemia was demonstrable in 8% of those with a pattern I response, in 54% of those with a pattern II response, and in 90% of those with a pattern III response (P less than 0.01). The pattern of response was unrelated to resting angiographic left ventricular ejection fraction, whether ST segments became elevated or depressed, or whether ischaemia was pacing-induced or spontaneous. These results suggest that the haemodynamic response to ischaemia is determined by the fraction of the left ventricle that becomes dysfunctional during ischaemia.

Blood Pressure↗
PubMed1979

Cardiomyopathic syndrome caused by coronary artery disease. III: Prospective clinicopathological study of its prevalence among patients with clinically unexplained chronic heart failure.

Each day, for one year, the medical records of adult patients who died in hospital were reviewed before seeing the necropsy findings. For those patients who had had chronic left or left and right heart failure, a presumptive cause was assigned on the basis of antemortem clinical data. Of 740 consecutive patients who were studied at necropsy, 90 had had chronic heart failure. In 15 patients the cause of heart failure was not apparent by clinical criteria; of these, 7 were found at necropsy to have cardiomyopathic syndrome caused by coronary artery disease. In retrospect, the presence of overt diabetes mellitus was a clue that cardiomyopathy caused by coronary artery disease was the cause of clinically unexplained heart failure; 5 of 7 patients with unexplained heart failure who were found to have this at necropsy were diabetic, whereas only 1 of the other 8 patients with clinically unexplained heart failure was diabetic (P less than 0.05). Patients in whom clinically unexplained heart failure was found to be the result of cardiomyopathy caused by coronary artery disease had multiple myocardial infarctions on pathological examination, which, with one exception, were nontransmural. By contrast, myocardial infarctions were transmural on pathological examination in each of 7 matched 'controls' with heart failure, in whom the diagnosis of coronary artery disease had been clinically apparent (P less than 0.01).

Adult↗
PubMed1979

Survival following mitral valve replacement for mitral regurgitation due to coronary artery disease.

Forty-six patients who underwent mitral valve replacement for mitral regurgitation due to coronary artery disease during 1970-1975 were identified. Forty patients underwent aortocoronary bypass procedures at the same operation. The survival rate at the fourth postoperative year was 73% in the 22 patients in whom the preoperative left ventricular ejection fraction exceeded 0.35, 38% in the 16 patients in whom the preoperative left ventricular ejection fraction was 35% or less, and 25% in the eight patients in whom aneurysmectomy was performed at the time of mitral valve replacement (p less than 0.05 for the former group compared to the latter two groups). Heart failure, present preoperatively in 41 patients, was improved in most of the long-term survivors. Neither the angiographic extent of coronary artery disease nor whether mitral valve replacement was performed in the acute (within 2 months in 13 patients) or chronic phase of myocardial infarction were distinctly correlated with survival.

Aged↗
PubMed1978

Synthesis of the four isomers of 5-hydroxy-PGI1.

We wish to report here the syntheses of (5S, 6R)-5-hydroxy-, (5R, 6R)-5-hydroxy-, (5R, 6S)-5-hydroxy-, and (5S, 6S)-5-hydroxy-PGI1 and their methyl ester derivatives. Treatment of (5R, 6S)-epoxy- and (5S, 6R)-epoxy-PGF1alpha methyl esters with acid washed silica gel afforded (5R, 6R)-5-hydroxy- and (5S, 6S)-5-hydroxy-PGI1 methyl esters; correspondingly, silica promoted cyclization of (5S, 6S)-epoxy- and (5R, 6R)-epoxy-PGF1alpha methyl esters yielded (5S, 6R)-5-hydroxy- and (5R, 6S)-5-hydroxy-PGI1 methyl esters. Alternatively, the 5-hydroxyl group was introduced into the PGI1 skeleton via reaction of the 5-mercuric halides with sodium borohydride in the presence of oxygen. Stereochemical assignments were based on their mode of synthesis and 1H nmr shift differences.

Prostaglandins↗
PubMed1978

Unexplained in-hospital fever following cardiac surgery. Natural history, relationship to postpericardiotomy syndrome, and a prospective study of therapy with indomethacin versus placebo.

In Part I of this study, the in-hospital course of 219 patients who had undergone a cardiac operation is analyzed. Fever (greater than or equal to 37.8 degrees C, rectal) was present after postoperative day 6 in 159 patients (73%) and was of unexplained cause in 118. Fever decay in the population of unexplained fever patients was exponential. All patients with unexplained postoperative fever were afebrile by postoperative day 19. In-hospital pericardial rub and pleuritic chest pain, widening of the mediastinum on chest film, and pleural effusion were not specifically associated with unexplained postoperative fever. In Part II, 67 patients with unexplained postoperative fever were given indomethacin (100 mg per day) or placebo for 7 days by a randomized, double-blind protocol. Indomethacin resulted in a shorter duration of fever (2.4 vs 3.5 days, P is less than 0.01) and in a shorter duration of chest pain, malaise, and myalgias compared to placebo. Sixty-seven percent of the patients in Part I and all of the patients in Part II were contacted 2-8 months following hospital discharge. Five percent had experienced an illness that we considered to be acute pericarditis, but its occurrence was unrelated to whether the patient had had in-hospital unexplained postoperative fever, in-hospital rub or chest pain, or in-hospital administration of indomethacin.

Cardiac Surgical Procedures↗