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R Jonas

Publications and source records attributed to R Jonas.

At least 37 records · Page 2Linked to original sources
PubMed1994

Structure and orientation of the transmembrane domain of glycophorin A in lipid bilayers.

Rotational resonance (RR) NMR, circular dichroism (CD), and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy are used to establish the secondary structure and orientation of peptides corresponding to the transmembrane domain of human glycophorin A in dimyristoylphosphatidylcholine bilayers. An amide I vibrational frequency of 1650 cm-1 and negative CD absorption bands at 208 and 222 nm indicate that the peptide is largely alpha-helical, while an order parameter of 0.35-0.50 in the ATR-FTIR measurements indicates that the peptide orientation is generally perpendicular to the bilayer plane. High-resolution structural data on the glycophorin A transmembrane (GPA-TM) peptides were obtained by measuring the rate of magnetization exchange between pairs of specific 13C labels using RR NMR. The exchange rates are translated into internuclear distances with a resolution on the order of 0.3 A. These experiments are similar in design to previous experiments on crystalline peptides where the 13C labels were incorporated into amino acids separated by 2-3 residues in the peptide sequence but close together in space due to a helical peptide geometry [Peersen, O.B., Yoshimura, S., Hojo, H., Aimoto, S., & Smith, S.O. (1992) J. Am. Chem. Soc. 114, 4332-4335]. In the GPA-TM peptides, magnetization exchange rates measured between [1-13C]V80 and [2-13C] G83 between [1-13C]M81 and [2-13C]G83 in the middle of the transmembrane sequence correspond to internuclear distances of approximately 4.5 A and are consistent with a helical peptide structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

The two mechanisms of action of racemic cardiotonic EMD 53998, calcium sensitization and phosphodiesterase inhibition, reside in different enantiomers.

The novel cardiotonic EMD 53,998 increases contractile force in vitro through both inhibition of phosphodiesterase III (PDE III) activity and increase in the responsiveness of the contractile proteins to calcium ("calcium sensitization"). Because EMD 53,998 is a racemate, the possibility arose that the two modes of action do not reside equally in the enantiomers. Therefore, the effects of the racemate and its two enantiomers [(+)EMD 57,033 and (-)EMD 57,439] were analyzed in guinea pig and rat cardiac tissue with respect to Ca2+ sensitization (Ca(2+)-induced force development in skinned cardiac myofibers and myofibrillar ATPase activity) and PDE III inhibition (isolated PDE isoenzymes and cyclic AMP level in isolated cardiac myocytes). In addition, the positive inotropic effects were compared in isometrically contracting papillary muscles. Enhancement of force of contraction (Fc) in submaximally activated skinned fibers showed a selectivity for the (+)enantiomer with EC50 = 1.7, 4.8, and > 100 microM for EMD 57,033, EMD 53,998, and EMD 57,439, respectively. Ca2+ concentration for half-maximal activation was decreased by 0.5 log units, and Cmax was increased by 15% at 10 microM EMD 57,033. Similarly, myofibrillar ATPase activity was most potently enhanced by the (+)enantiomer, with EC50 values of 1.8, 2.5, and > 30 microM for EMD 57,033, EMD 53,998, and EMD 57,439, respectively. PDE III activity was inhibited with greater potency by the (-)enantiomer, with IC50 values of 0.05, 0.06, and 1.94 microM for EMD 57,439, EMD 53,998, and EMD 57,033, respectively. The cyclic AMP content of isoprenaline-stimulated rat cardiac myocytes was increased by 50% at 13.6 and 0.71 microM for EMD 57,033 and EMD 57,439, respectively. In intact guinea pig papillary muscle, the positive inotropic effect of the (+)enantiomer was insensitive to isoprenaline pretreatment; in contrast, the (-)enantiomer showed only a weak positive inotropic action which was strongly enhanced in the presence of isoprenaline. We conclude that one of the two different mechanisms underlying the overall positive inotropic activity of EMD 53,998 can be assigned, almost exclusively, to one of the two enantiomers. Thus, the (-)enantiomer EMD 57,439 is a "pure" PDE III inhibitor with almost no Ca2+ sensitizing activity; the (+)enantiomer EMD 57,033 is a potent Ca2+ sensitizer with only a weak PDE III inhibitory activity as compared with the racemate. In contrast to other compounds with mixed activity, EMD 57,033 is unique in possessing both a high absolute potency at the level of the contractile elements and a favorable relation of Ca2+ sensitization to PDE inhibition.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Type A behavior pattern and emotion expression in younger and older adults.

Eighty younger (less than 50 years, M = 28 years) and 80 older (more than 50 years, M = 69 years) Type A and Type B Ss were evaluated for Type A behavior pattern using the Structured Interview (SI) and given personality tests for anxiety, depression, anger, aggression, hostility, and anger-in-anger-out. Ss also underwent an emotion induction procedure. Videotapes of the emotion induction procedure (N = 160) and the SI (N = 80) were coded for facial expression of emotion. Type As did not differ from Bs on anxiety or depression but did on anger and aggression. Type As showed anger inhibition and anger bound to shame, as predicted by emotion socialization theory. The greatest number of differential effects were observed between age groups. Older individuals, in general, were more emotionally expressive than younger Ss across a range of emotions. Women appeared more conflicted about anger expression than men, and Type A women more so than Type A men.

Adult↗
PubMed1992

Novel diazinone derivatives separate myofilament Ca2+ sensitization and phosphodiesterase III inhibitory effects in guinea pig myocardium.

The inotropic state of the myocardium can be enhanced via an increase in cell Ca2+ loading or in myofilament responsiveness to Ca2+. Although different pharmacological agents combine these properties, no presently available drug acts predominantly as a myofilament sensitizer in situ. We have investigated the effects and the mechanism of action of novel diazinone derivatives, EMD 54622, EMD 53998, and EMD 54650 (developed by E. Merck, Darmstadt), on guinea pig myocardial preparations. Force- and ATPase-pCa relations in skinned fibers show differing potencies of these agents on myofilament sensitization: EMD 54622 greater than EMD 53998 much greater than EMD 54650. This is in contrast to their relative potencies to inhibit isolated myocardial phosphodiesterase III: EMD 54650 greater than EMD 53998 greater than EMD 54622. In isolated hearts studied at constant coronary flow, each of the three diazinone derivatives had a positive inotropic effect. In enzymatically dissociated left ventricular myocytes loaded with the Ca2+ probe indo-1, the positive inotropic effect of EMD 54622 occurred with no change in the amplitude of the cytosolic [Ca2+] (Cai) transient. In contrast, both EMD 53998 and EMD 54650 enhanced Cai transient and twitch contraction amplitudes. Length-indo-1 fluorescence relations were analyzed to determine the effects of the three substances on myofilament responsiveness to Ca2+. EMD 54622 enhanced and EMD 54650 had no effect on myofilament responsiveness to Ca2+. Less uniform results were obtained with EMD 53998 (in two of five cells the myofilament responsiveness to Ca2+ was increased, whereas in three other cells it was unaltered). Our results indicate that structural changes in the diazinone molecule shift the mechanism of action for the positive inotropic effect of the diazinone derivatives in the intact cell from a predominant myofilament sensitization (EMD 54622) to an enhancement in cell Ca2+ loading and an augmentation in the Cai transient (EMD 54650).

Actin Cytoskeleton↗
PubMed1991

Binding of a single divalent cation directly correlates with the blue-to-purple transition in bacteriorhodopsin.

We have characterized a unique divalent cation binding site on bacteriorhodopsin which controls the blue-to-purple transition in the purple membrane of Halobacterium halobium. To identify this site we first showed the correlation between the binding of one Ca2+ per bacteriorhodopsin and the amount of blue membrane converted to purple membrane. When the free Ca2+ was reduced below 1 microM, and the pH was set below 5.0 with 0.5 mM citrate, only binding to this high-affinity site was observed, and we could separate its effect from the effect of other divalent cations binding to the membrane under other conditions. Second, the titration of purple membrane showed that protons are taken up in two distinct steps, about 13 with a pKa of 4-5 and an additional 2 protons with a pKa of 2.75, in 5 mM MgSO4. The latter is identical to the pKa for the purple-to-blue transition in 5 mM MgSO4. Taken together, these observations strongly suggest a direct role for cations in the regulation of the bacteriorhodopsin color under normal conditions. We have also found that the intrinsic pKa for the purple-to-blue transition is about 2.05, suggesting this is the pKa of the group or groups that, when protonated, lead to the blue membrane. Previously published data can now be interpreted to suggest that the cation regulates an active site near the retinal chromophore. A binding site for the divalent cation that includes Asp-212 and interactions with the protonated Schiff base, Asp-85, Tyr-57, Tyr-185, and Arg-82 is proposed.

Journal Article↗
PubMed1991

The novel cardiotonic agent EMD 53 998 is a potent "calcium sensitizer".

EMD 53 998, a novel thiadiazinone derivative, increases the contractile force of cardiac tissue in vitro through both an inhibition of phosphodiesterase III (PDE III) and a sensitization of cardiac contractile proteins to Ca2+. Guinea pig ventricular PDE III is selectively inhibited by EMD 53 998 (IC50 = 60 nM) without major effects on other PDE isoenzymes. Consonant with this is an increase in cAMP content of rat ventricular cells and a potentiation by EMD 53 998 of the cAMP-elevating action of isoprenaline (increase by 50% at 1.3 microM). Sensitization to Ca2+ by EMD 53 998 (3-30 microM) finds its expression in a leftward shift of the Ca2+ response curve for force generation in skinned fibers from porcine ventricular muscle and failing human heart as well as for activation of bovine cardiac myofibrillar actomyosin ATPase. Interestingly, EMD 53 998 elevates the maximum of the Ca(2+)-response curve for both parameters. Pimobendan studied under identical conditions was 100 times less potent than EMD 53 998. EMD 53 998 increases force development of guinea pig papillary muscle in a concentration-dependent manner with an EC50 of 3.6 microM, thus being 10 times more potent than pimobendan. In contrast to pimobendan, the positive inotropic effect of EMD 53 998 is barely affected by carbachol. Further evidence for a Ca(2+)-sensitizing effect of EMD 53 998 is provided by an additional increase in force generation in the presence of supramaximal isoprenaline concentrations. It is concluded that the positive inotropic action of EMD 53 998 is mediated through both cAMP-independent and cAMP-dependent mechanisms, with the former probably prevailing. We are not aware of other compounds with a similarly high Ca(2+)-sensitizing potency. On these grounds. EMD 53 998 appears to be a promising inotropic agent.

Adenosine Triphosphatases↗
PubMed1989

Imidazopyridines: roles of pyridine nitrogen position and methylsulfinyl oxygen for in vitro positive inotropic mechanism and chronotropic activity.

The role of structural features of sulmazole, an imidazo(4,5-b)pyridine, in its inotropic action was examined by comparison with its reduced (4-methylthiophenyl) analog EMD 46512 and the corresponding imidazo(4,5-c)pyridine isomers isomazole and EMD 41000 on isolated guinea-pig papillary muscles and right atria and on Na,K-ATPase and phosphodiesterase III isolated from guinea-pig hearts. The pyridine nitrogen position in sulmazole was crucial for affinity to Na,K-ATPase (IC50 = 350 microM) because the imidazo(4,5-c)pyridines had little effect. Participation of Na,K-ATPase inhibition in sulmazole's inotropic effect (EC50 = 180 microM) was suggested by synergism with the Na channel activator germitrine. The methylsulfinyl oxygen at the phenyl ring decreased the affinity to Na,K-ATPase of sulmazole 40-fold: The reduced analog EMD 46512 was a potent inhibitor of Na,K-ATPase (IC50 = 8.5 microM) and a more potent inotropic agent (EC50 = 8.2 microM) that appeared to act predominantly through Na,K-ATPase inhibition. Micromolar through Na,K-ATPase inhibition. Micromolar IC50s for inhibition of phosphodiesterase III were 49 (sulmazole), 34 (EMD 46512), 18 (isomazole), and 13 (EMD 41000). Participation of this mechanism in the inotropic effect of sulmazole, isomazole, and EMD 41000, but not EMD 46512, was indicated by augmentation of slow action potentials, synergism with histamine, inhibition by carbachol, and (with the exception of EMD 41000) a positive chronotropic effect on the right atrium. Sulmazole appeared to combine the actions of its 4-methylthiophenyl analog EMD 46512 (an inhibitor of Na,K-ATPase) and of its imidazo(4,5-c)pyridine isomer isomazole (an inhibitor of phosphodiesterase III).

Action Potentials↗
PubMed1988

Concentrations of ketone bodies in the blood of the green lizard Ameiva ameiva (Teiidae) in different physiological situations.

1. The concentrations of acetoacetate and 3-hydroxybutyrate have been determined in the blood of the green lizard Ameiva ameiva (Teiidae) in fed animals and in animals starved for periods from one week to about four months. 2. The concentrations of acetoacetate are low and unaltered in fed and starved animals, being in the range from 0.014 to 0.018 mM. 3. The concentrations of 3-hydroxybutyrate are high: 2.67 mM, in fed animals, falling during starvation down to 0.26 mM. 4. The 3-hydroxybutyrate/acetoacetate ratio is high, 151, in fed animals, falling down to 17. 5. The possible importance of ketone bodies in the metabolism of Ameiva ameiva is discussed.

3-Hydroxybutyric Acid↗
PubMed1988

Tetralogy of Fallot with obstruction of the ventricular septal defect: spectrum of echocardiographic findings.

Tetralogy of Fallot with a restrictive ventricular septal defect and suprasystemic right ventricular pressure is an uncommon anomaly with a high mortality rate. In previous studies, the identity of the tissue obstructing the ventricular septal defect has usually not been determined preoperatively. This report describes the echocardiographic and anatomic features in 4 patients with a restrictive ventricular septal defect among 269 patients with tetralogy of Fallot undergoing surgical repair. Echocardiography determined the presence and identity of the obstructing tissue in all four patients. In one patient, the defect was small in association with marked septal hypertrophy. In three patients, accessory or excessive tricuspid valve tissue obstructed the defect in a manner similar to spontaneous closure of isolated membranous ventricular septal defects. Autopsy and catheterization findings are also presented of an additional case with a unique mechanism of obstruction by a tricuspid valve with Ebstein's anomaly. In patients with tetralogy of Fallot, recognition of an obstructed ventricular septal defect is important because it appears to have a poor prognosis.

Echocardiography↗
PubMed1987

The relation between low facial expressivity during emotional arousal and somatic symptoms.

Differential emotions theory has suggested that suppressed emotion, and specifically suppressed facial signs of emotion, might be aetiologically associated with illness, and moreover, that suppression of different classes of emotion might be related to differential symptom formation. This study examined the relationship between degree of facial emotional expressivity under conditions of emotional arousal and the presence and extent of various self-reported physical symptoms. Twenty-three adult women underwent emotion induction procedures and were videotaped while they described their emotional reactions. Judges viewed the videotapes of subjects' facial behaviour and rated the degree of expressivity during the sadness, fear, and anger inductions. Correlational statistics indicated that physical symptoms were almost exclusively negatively correlated with emotion expression. There was also some evidence of an emotion-specific/symptom-specific configuration. Although causal inferences about emotion-symptom linkages are unwarranted at this time, the study provides some support for theoretical formulations about the relationship between physical symptoms and emotion and suggests a methodology with which to pursue this line of research.

Adolescent↗
PubMed1986

The restriction endonuclease Alu I induces chromosomal aberrations in human peripheral lymphocytes in vitro.

The restriction endonuclease Alu I (recognition site AG/CT) produces chromosomal aberrations in isolated human peripheral lymphocytes in vitro. The aberrations are of the chromosome-type when the cells are treated in G1 and of the chromatid-type when the cells are treated in late S, early G2. Additional treatment with ammonium sulphate leads to higher aberration frequencies than treatment with Alu I alone.

Ammonium Sulfate↗
PubMed1986

Metabolism of ethanol in vitro produces a compound which induces sister-chromatid exchanges in human peripheral lymphocytes in vitro: acetaldehyde not ethanol is mutagenic.

Ethanol (EtOH) in the presence of the EtOH-metabolizing enzyme, alcohol dehydrogenase (ADH) leads to the induction of sister-chromatid exchanges (SCEs) in human peripheral lymphocytes in vitro. Acetaldehyde (AA) induces SCEs, whose frequencies are lowered in the presence of the AA-metabolizing enzyme, aldehyde dehydrogenase (ALDH). EtOH in the presence of ADH produces more SCEs than EtOH in the presence of ADH and ALDH. These data are interpreted to show that not ethanol itself, but its first metabolite acetaldehyde is mutagenic.

Acetaldehyde↗
PubMed1986

Pharmacodynamic profile of the selective beta 1-adrenoceptor antagonist bisoprolol.

The pharmacodynamic activity of (+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2- propranol- hemifumarate (bisoprolol, EMD 33 512) has been investigated under in vitro and in vivo conditions. Bisoprolol was found to be an effective beta-adrenoceptor antagonist, the pA2 values determined against isoprenaline in guinea pig atria and tracheal muscle being 7.45 and 6.41, respectively. Thus, the selectivity ratio of bisoprolol in favour of beta 1-adrenoceptors is 11. Inhibition of the isoprenaline-induced tachycardia in guinea pigs indicated a long duration of action for bisoprolol. The compound was devoid of intrinsic sympathomimetic activity as shown by the lack of effect on heart rate in anaesthetized and reserpine pretreated rats. Studies in rabbits and guinea pigs revealed a local anaesthetic activity of bisoprolol at high concentrations. Bisoprolol protected the hearts of anaesthetized dogs against the sequelae of intermittent coronary occlusions, as judged by the reduction of the ST-segment elevation in the epicardial ECG. Bisoprolol exerted a blood pressure lowering effect in conscious renal hypertensive dogs after oral administration of 30 micrograms/kg. There was no indication of any action on the CNS in monkeys following an oral dose of up to 8 mg/kg.

Adrenergic beta-Antagonists↗
PubMed1985

Extravascular lung water in children immediately after operative closure of either isolated atrial septal defect or ventricular septal defect.

Extravascular lung water (EVLW) was measured in 16 patients with congenital heart disease by the cold green dye, double indicator dilution technique. Five patients with optimally corrected tetralogy of Fallot served as controls, and EVLW in this group was 4.7 +/- 0.5 ml/kg (111 +/- 13 ml/m2) (mean +/- standard deviation). In 5 asymptomatic patients with atrial septal defect (ASD), normal pulmonary artery (PA) pressure and increased pulmonary blood flow, EVLW was 5.7 +/- 2.8 ml/kg (132 +/- 63 ml/m2), which was not significantly different from the value of control patients. However, in 6 patients with ventricular septal defect, PA hypertension, normal left atrial pressure and an equivalent left-to-right shunt to ASD patients, EVLW was 15.9 +/- 3.8 ml/kg (270 +/- 60 ml/m2). This was significantly different from values in both control and ASD patients (p less than 0.01). It is concluded that in the face of normal pulmonary vascular resistance, PA pressure is transmitted to the microvasculature, causing hydrostatic pulmonary edema. Other factors that may be implicated in the pathogenesis of pulmonary edema, such as increased pulmonary blood flow and relative lymphatic insufficiency in infants, cannot be excluded.

Child↗
PubMed1985

The analgesic effects of aspirin and placebo on experimentally induced tooth pulp pain.

We examined the relative analgesic potency of aspirin and placebo in a within-subject-repeated-measure experiment using a precision tooth pulp stimulation technique with long-term stability (r = 0.93) for more than two months between measures. The attenuation of pain perception was evaluated using a standardized magnitude estimation procedure and constructing an individual psychophysical function for each trial. The data were fit equally well by either a straight line (Y = mX + b) or a power function (Y = mXa + b). Using the line fit and distribution insensitive conservative statistical tests, the effect of each treatment was compared to baseline and the treatments were compared to each other. In randomized, double-blind trials we found reliable effects of both aspirin (p less than 0.001) and placebo (p less than 0.001) but no difference (p = 0.08) between these two treatments. However, on an individual basis, 12 of 17 subjects displayed a larger analgesic response to aspirin than to placebo (p less than 0.05).

Adolescent↗