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H Sigel

Publications and source records attributed to H Sigel.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Preclinical resuscitation--which factors influence the long-term course? A 5-year follow-up].

OBJECTIVE: The factors that influence long-term survival after out-of-hospital resuscitations were investigated. PATIENTS AND METHODS: Between 1985 and 1989, out of a total of 8403 responded emergency calls, 505 resuscitations were undertaken out of hospital by the emergency medical service in Göppingen. All emergency calls were recorded uniformly. Of the 505 resuscitations, 154 were primarily successful (30.5%), and 58 were secondarily successful, i.e. the patients were ultimately discharged from hospital. In 56 of them the further course could be followed at least 5 years after the resuscitation (45 males, 11 females; mean age 57 [10-83] years). The patients' charts were analysed; in 51 cases data could be obtained from the family doctor, from ambulant care or from home visits. RESULTS: 34 patients (60.4%) were still alive 5 years after the resuscitation. The highest death rate (16%) was in the first post-resuscitation year. Prognostically unfavourable factors were: advanced age (P < 0.01), underlying cardiac disease (n = 49; P < 0.025), especially coronary heart disease (n = 34; P < 0.01). Patients with primary ventricular fibrillation and previous myocardial infarction (n = 10) had a poorer prognosis than those with acute infarction (n = 24; P < 0.05). Reduced survival chances occurred in those with impaired left ventricular function, as measured echocardiographically (P < 0.05), or with cardiac arrhythmias, Lown classes III and IV (P < 0.05), as well as in those with severe neurological sequelae (n = 8; P < 0.08). CONCLUSION: Long-term prognosis depends, in the first instance, on the resuscitated patient's basic condition and not so much on the circumstances of the resuscitation.

Adolescent↗
PubMed1995

[High-grade coronary stenosis due to a bronchogenic cyst].

A 32-year-old woman without preceding illness or significant cardiovascular risk factors was admitted to hospital because of a syncope after physical exertion. Transoesophageal echocardiography, performed to exclude aortic dissection, showed as an incidental finding a cystic space-occupying mass, 5 x 6 cm in diameter, dorsal to the aortic root and main pulmonary artery. Exercise ECG had S-T segment depressions of about 0.3 mV, associated with anginal symptoms, so that inadequate coronary artery flow on exertion was suspected. Subsequent coronary angiography demonstrated a funnel-shaped 80% stenosis at the origin of the main left coronary artery, while all other coronary arteries were normal and smooth-walled. A causal connection between the two findings was assumed and quickly undertaken surgical intervention revealed an intrapericardial bronchogenic cyst which, presumably as a result of its size and location, had pressed on the main stem of the left coronary artery and caused the stenosis of its ostium. The cyst was completely resected and angioplasty of the coronary artery ostium was performed to ensure its patency. 3 months postoperatively the patient underwent an exercise test of up to 125 Watt without signs of ischaemia. This case presents a previously unreported complication of a bronchogenic cyst.

Adult↗
PubMed1994

[Pacemaker therapy for the sick sinus node syndrome. Does the atrially involved pacemaker system lower the frequency of atrial fibrillation and thromboembolic complications as well as mortality?].

Between 1986 and 1992, pacemakers were implanted in 307 patients with symptoms caused by the sick sinus syndrome (SSS). 301 patients were regularly followed up (161 men, 146 women, mean age 72.9 [27-91] years) of whom 180 had a VVI, 65 and AAI and 58 a DDD/DDI pacemaker. Mean follow-up period was 58.3 months for VVI-stimulated patients and 35.6 months for atrial paced patients. The data were analysed retrospectively to ascertain whether a change in pacemaker treatment to a more physiological system produced any lowering in the mortality rate, incidence of permanent atrial fibrillation (AF), and thromboembolic phenomena. The annual mortality rate of the VVI-stimulated patients was 6.9%, that of atrial paced patients 2.8%. Age, abnormal ventricular function, survived resuscitation and diabetes mellitus each correlated with a shortened life expectancy already at the time of implantation, regardless of the pacemaker mode. Permanent AF was more frequent during VVI stimulation (16% vs 7%), especially if it had been preceded by intermittent AF (26% vs 13%). But there was no significant difference with regard to transitory cerebral ischaemic episodes and peripheral arterial emboli (15% vs 10%). Fewer patients with atrial pacing went into heart failure (20% vs 30%). Four patients developed a high-grade atrioventricular (a-v) block on AAI stimulation (annual incidence 2.4%). - These observations suggest that patients with SSS should always have atrial paced pacemaker systems. If a-v conduction is disturbed, a bifocal pacemaker is the system of choice.

Adult↗
PubMed1991

Acid-base properties of nucleosides and nucleotides as a function of concentration. Comparison of the proton affinity of the nucleic base residues in the monomeric and self-associated, oligomeric 5'-triphosphates of inosine (ITP), guanosine (GTP), and adenosine (ATP).

The acid-base properties of the nucleic base residues of ITP, GTP, and ATP, and for comparison also as far as possible of the corresponding nucleosides, were studied in dependence on their concentration, i.e. on the effect of self-association. From the dependence between the 1H-NMR chemical shifts of H-2 (where applicable), H-8, and H-1', and the pD of the solutions, the acidity constants for the deprotonation of the D+(N-7) site in D2(ITP)2-, D2(GTP)2-, D(Ino)+, and D(Guo)+, and of the D+(N-1) site in D2(ATP)2- and D(Ado)+ were calculated. Chemical shift/pD profiles for a whole series of varying concentrations of the nucleic base derivatives (= N) were constructed, including those for infinite dilution (delta o), which give the acidity constant for the monomeric N, and for infinitely concentrated solutions (delta infinity), which give the acidity constant of an N in an infinitely long stack. The acidity constants determined from the delta o/pD plots are in excellent agreement with the pKa values measured by potentiometric pH titrations of highly diluted solutions of N. The effects of self-association are striking; e.g. the pKa value of the D+(N-7) site in D2(GTP)2- is lowered by about 1 (as calculated from the delta o/pD and delta infinity/pD profiles), while the pKa value of the D+(N-1) site in D2(ATP)2- is increased by approximately 0.3; i.e. in the first case deprotonation is facilitated and in the second it is inhibited. The increasing inhibition of the H+(N-1) deprotonation with an increasing ATP concentration is due to the high stability of the dimeric [H2(ATP)]2(4-) stack for which the intermolecular H+(N-1)/gamma-P(OH)(O)2- ion pairs between the two ATP molecules are crucial. In those cases where no other significant interaction but aromatic-ring stacking in the self-association process occurs, the release of protons from protonated nitrogen-ring sites is facilitated with increasing stacking; this holds not only for D2(GTP)2- as indicated above, but also for D2(ITP)2-, D(Ino)+, and D(Ado)+. The latter example especially suggests that the situation for the D2(ATP)2- system is exceptional. Some consequences of the considered acid-base properties for biological systems are indicated.

Adenosine↗
PubMed1990

Comparison of the self-association properties of the 5'-triphosphates of inosine (ITP), guanosine (GTP), and adenosine (ATP). Further evidence for ionic interactions in the highly stable dimeric [H2(ATP)]2(4-) stack.

The concentration dependence of the chemical shifts for the hydrogens H-2, H-8 and H-1' of ITP and for H-8 and H-1' of GTP has been measured in D2O at 25 degrees C under several degrees of protonation in the pD range 1.2-8.4. For reasons of comparison, inosine and guanosine have been included in the study The results are consistent with the isodesmic model of indefinite noncooperative stacking. The association constants for the nucleosides (Ns) inosine and guanosine decrease with increasing protonation: Ns greater than D(Ns)+/Ns in a 1:1 ratio greater than D(Ns)+. In contrast, a maximum is observed with ITP and GTP; the stacking tendency of GTP following the series: GTP4- less than or equal to D(GTP)3- (K approximately 0.7 M-1) less than D(GTP)3-/D2(GTP)2- in a 1:1 ratio (K approximately 2.9 M-1) greater than D2(GTP)2- greater than D3(GTP)- (K approximately 1.5 M-1). The order of the series with ITP corresponds to that with GTP, but the association constants are slightly smaller. At the maximum of the self-association tendency the triphosphate residue has only a minor influence; this follows from the fact that the association constants for the 1:1 ratios of Ino/D(Ino)+ and D(ITP)3-/D2(ITP)2- are identical within experimental error; this holds also for Guo/D(Guo)+ and D(GTP)3-/D2(GTP)2-; in all these pairs the K-7 site is 50% protonated. Comparison of the association constant for the deprotonated species shows that here charge effects, i.e. repulsion between the negatively charged triphosphate chains, are important: Ino (K approximately 3.3 M-1) greater than ITP4- (K approximately 0.4 M-1) and Guo (K approximately 8 M-1) greater than GTP4- (K approximately 0.8 M-1). In addition the series holds: Ado (K approximately 15 M-1) greater than Guo greater than Ino. However, most important is the comparison of the ITP and GTP series with previous data for ATP: ATP4- (K approximately 1.3 M-1) less than D(ATP)3- (2.1 M-1) less than 1:1 ratio of D(ATP)3-/D2(ATP)2- (6 M-1) much less than D2(ATP)2- (approximately 200 M-1) much greater than D3(ATP)- (K less than or equal to 17 M-1).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1990

Metal-ion-governed molecular recognition: extent of intramolecular stack formation in mixed-ligand--copper(II) complexes containing a heteroaromatic N base and an adenosine monophosphate (2'AMP, 3'AMP, or 5'AMP). A structuring effect of the metal-ion bridge.

Stability constants of mixed-ligand Cu(Arm)(AMP) complexes [where Arm = 2,2'-bipyridyl (Bpy) or 1,10-phenanthroline (Phen) and AMP2- = 2'AMP2-, 3'AMP2- or 5'AMP2-] were determined by potentiometric pH titrations in aqueous solution at I = 0.1 M (NaNO3) and 25 degrees C. The ternary Cu(Arm)(AMP) complexes are more stable than corresponding Cu(Arm)(R-MP) complexes, where R-MP2- represents a phosphate monoester with a group R that is unable to participate in any kind of interaction within the complexes as, for example, D-ribose 5'-monophosphate. This increased stability is attributed, in agreement with previous results, to intramolecular stack formation in the Cu(Arm)(AMP) complexes between the purine residue of the AMPs and the aromatic rings of Bpy or Phen. Based on correlation lines (previously obtained from log K versus pKa plots) for Cu(Arm)(R-MP) complexes without a ligand-ligand interaction, a quantitative evaluation was carried out. The degree of formation of the species with the intramolecular stacks increases for the Cu(Arm)(AMP) complexes in the series: 3'AMP2- less than 5'AMP2- less than 2'AMP2-; e.g. in Cu(Bpy)(3'AMP) the stack reaches a formation degree of 45 +/- 11% and in Cu(Bpy)(2'AMP) one of 96.1 +/- 0.7% is obtained. It must be emphasized that these differences are due to the different steric orientations of the bridging metal ion, which result from the varying position of the phosphate group on the ribose ring. As shown by 1H-NMR shift measurements, there is no significant effect of the position of the phosphate group on the stability of the binary (Phen)(AMP)2- adducts (K approximately 36 M-1 in D2O); such an effect is seen only if a metal-ion bridge is formed between the moieties forming the stack, i.e. metal-ion coordination imposes individual properties on the AMPs. By also taking into account some recent results on other nucleoside 5'-monophosphate complexes, the following trend for an increasing stacking tendency of the nucleic base moieties can be established: uracil approximately less than cytosine approximately less than thymine much less than adenine less than 7-deazaadenine. Some additional conclusions of general importance are given and the relevance of the results with regard to bio-systems is indicated.

Adenosine Monophosphate↗
PubMed1989

[Radionuclide ventriculography. The significance of global and regional ejection fractions and Fourier amplitude and phase in the diagnosis of exertion-dependent ischemia].

Electrocardiograms and radionuclide ventriculograms were obtained at rest and on exercise in 23 patients (20 men and 3 women, mean age 53.4 years) with exercise-dependent myocardial ischaemia after infarction, as well as in 22 persons (17 men and 5 women, mean age 43 years) without clinical, electrocardiographic and biochemical evidence of coronary heart disease. Among the ischaemia patients exercise-dependent loss of motility, as measured by regional ejection fraction and Fourier amplitude, occurred in 95% (50% of controls) in one sector, in 78% (4.5% of controls) in the two sectors with the highest contractility at rest, and in 74% (0% of controls) in three sectors. On exercise, phase shifts occurred in 87% (27% of controls). When combining the exercise-ECG, global ejection fraction as well as regional motility loss in one sector, in the two sectors with the highest contractility at rest and in three sectors, at least two of the five criteria of abnormality were present in 91.3% of the ischaemia patients, compared with at most one criterion in 90.9% of controls. The results indicate the greater diagnostic value of regional than global measures of ventricular function and emphasize the importance of radionuclide ventriculography as an addition to exercise electrocardiography in the pre-invasive diagnosis of coronary heart disease.

Adult↗
PubMed1989

Evaluation of the metal-ion-coordinating differences between the 2'-, 3'- and 5'-monophosphates of adenosine.

The stability constants of the 1:1 complexes formed between Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+ or Cd2+ and 2'AMP2-, 3'AMP2- or 5'AMP2- were determined by potentiometric pH titration in aqueous solution (I = 0.1 M, NaNO3; 25 degrees C). The experimental conditions were carefully selected such that self-association of the nucleotides and their complexes is negligibly small; i.e. it was made certain that the properties of the monomeric divalent-metal-ion--AMP [M(AMP)] complexes were studied. Based on recent measurements with simple phosphate monoesters, R-MP2- where R is a non-coordinating residue [Massoud, S. S. & Sigel, H. (1988) Inorg. Chem. 27, 1447-1453], it is shown that all the M(AMP) complexes of the alkaline earth ions, with the possible exception of Mg(5'AMP), have exactly the stability expected for a sole-phosphate coordination of the metal ion. The same property is revealed for the complexes with Mn2+, Co2+, Zn2+ or Cd2+ and 3'AMP2-; in case of Ni(3'AMP) and Cu(3'AMP) a slight stability increase just at the edge of the experimental-error limits is indicated. This slight stability increase is attributed to the formation of a macrochelate (possibly with N-3); in fact, additional information confirms macrochelation for Cu(3'AMP). About 45% of Cu(2'AMP) exists in aqueous solution as a macrochelate (probably involving N-3); the other M(2'AMP) complexes (M2+ = Mn2+, Co2+, Ni2+, Zn2+, Cd2+) form (if at all) only traces of a base-backbound species. Most pronounced is macrochelate formation with 5'AMP2-: all mentioned 3d ions and Zn2+ or Cd2+ form to some extent macrochelates via N-7 (the structures of these closed species are indicated). In case of M(5'AMP) the base-binding site is certain: replacement of N-7 by a CH unit (tubercidin 5'-monophosphate) eliminates any increased complex stability, whereas formation of the 1,N6-etheno bridge to form 1,N6-ethenoadenosine 5'-monophosphate results in the phenanthroline-like N-6,N-7 site which facilitates macrochelation significantly.

Adenosine Monophosphate↗
PubMed1989

Pharmacokinetic and pharmacodynamic properties of ramipril in patients with congestive heart failure (NYHA III-IV).

To investigate the pharmacokinetics and pharmacodynamics of a new angiotensin converting enzyme (ACE) inhibitor, ramipril (HOE 498), in patients with cardiac insufficiency (NYHA III-IV), we performed an open trial with a follow-up of 10 days. Twenty-seven patients (18 females, 9 males), mean aged 62 years (46-83) with severe heart failure, were included. After a single oral dose of 5 mg ramipril, the plasma and urine levels of ramipril, ramiprilat, ACE plasma activity, standard laboratory values, blood pressure and pulse rate were evaluated. The maximal plasma level of ramipril was 57.0 +/- 26.8 ng/ml after 1.4 h; t1/2 was 2.4 +/- 1.2 h. The peak level of ramiprilat was 27.9 +/- 24 ng/ml after 4.6 h; t1/2 for the active compound was 6 +/- 4.2 h. The total recovery of ramipril and metabolites in urine was on average 39 +/- 17.5% within 96 h. Ninety-five percent inhibition of ACE activity was observed in all patients and 80% inhibition lasted 24 h. Systolic and diastolic blood pressure decreased without changes in heart rate. Five patients had mild side effects: hypotension, diarrhea, and dizziness. In conclusion, in patients with severe heart failure, plasma levels of drug and active metabolite were higher and remained measurable longer, with more sustained inhibition of ACE activity than reported in healthy volunteers. This indicates that titration should start with lower doses (1.25-2.5 mg) and that doses above 5 mg may rarely be necessary.

Administration, Oral↗
PubMed1988

Influence of the protonation degree on the self-association properties of adenosine 5'-triphosphate (ATP).

The concentration dependence of the chemical shifts for the protons H-2, H-8 and H-1' of ATP has been measured in D2O at 27 degrees C under several degrees of protonation in the pD range from 1.5 to 8.4. The results at pD greater than 4.5 are consistent with the isodesmic model of indefinite noncooperative stacking, while those at pD less than 4.5 indicate a preference for the formation of dimeric stacks. The stacking tendency follows the series, ATP4- (K = 1.3 M-1) less than D(ATP)3- (2.1 M-1) less than 1:1 ratio of D(ATP)3-/D2(ATP)-2- (6.0 M-1) much less than D2(ATP)2- (approximately 200 M-1) much greater than D3(ATP)- (K approximately less than 17 M-1) (for reasons of comparison all constants are expressed in the isodesmic model). These results are compared with previous data for adenosine [Ado (K = 15 M-1) greater than 1:1 ratio of Ado/D(Ado)+ (6.0 M-1) greater than D(Ado)+ (0.9 M-1)] and AMP [AMP2- (K = 2.1 M-1) less than D(AMP)- (3.4 M-1) less than 1:1 ratio of D(AMP)-/D2(AMP) +/- (5.6 M-1) greater than D2(AMP) +/- (approximately equal to 2 M-1) greater than D3(AMP)+ (K less than or equal to 1 M-1)] to facilitate the interpretation of the results for the ATP systems. Stack formation of H2(ATP)2- is clearly favored by additional ionic interactions; this is confirmed by measuring via potentiometric pH titrations the acidity constants of H2(ATP)2- in solutions containing different concentrations of ATP. It is suggested that in the [H2(ATP)]4-(2) dimer intermolecular ion pairs (and hydrogen bonds) are formed between the H+(N-1) site of one H2(ATP)2- and the gamma-P(OH)(O)-2 group of the other; in this way (a) the stack is further stabilized, and (b) the positive charges at the adenine residues are compensated (otherwise repulsion would occur as is evident from the adenosine systems). A detailed structure for the [H2(ATP)4-(2) dimer is proposed and some implications of the described stacking properties of ATP for biological systems are indicated.

Adenosine Triphosphate↗
PubMed1987

Radionuclide ventriculography and hemodynamic evaluation by right heart catheterization with exercise for assessing the functional significance of coronary artery stenoses. A comparative study.

A series of 13 patients with significant coronary stenoses but without prior myocardial infarction were simultaneously studied by right heart catheterization and radionuclide ventriculography to determine the extent to which abnormal responses in left ventricular ejection fraction and wall motion to maximum exercise are paralleled by abnormal left ventricular filling pressures. The correlations of the filling pressure as evaluated by the diastolic pulmonary artery pressure with both the exercise ejection fraction and the rest-to-exercise change in ejection fraction were high (r = -0.89, P less than 0.01 and r = -0.76, P less than 0.01, respectively). In addition, the filling-pressure response to stress separated the patients into distinct radionuclide categories. All the 7 patients with grossly abnormal filling pressures (P greater than or equal to 30 mmHg) developed regional wall motion abnormalities with exercise as evaluated by visual interpretation or quantitative phase analysis. These patients also had a decrease in ejection fraction from rest to exercise ranging from -9% to -32% together with an exercise ejection fraction below 50%. Conversely, these abnormalities were never found in patients with filling pressures below this threshold level. The data suggest that radionuclide ventriculography and measurement of left ventricular filling pressure with exercise yield corresponding results when assessing the functional significance of coronary stenoses in normotensive patients without prior myocardial infarction and normal global left ventricular function at rest.

Blood Pressure↗
PubMed1987

Isomeric equilibria in complexes of adenosine 5'-triphosphate with divalent metal ions. Solution structures of M(ATP)2- complexes.

Solution structures of M(ATP)2- complexes are reviewed. First the self-stacking properties of ATP4- and M(ATP)2- are shortly described. It is emphasized that for an evaluation of solution structures of M(ATP)2- complexes only results from diluted solutions (below 1 mM) should be used. Next, a comprehensive set of stability data obtained under such conditions from potentiometric pH titrations is summarized for the complexes of Mg2+, Ca2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+ and Cd2+ with ATP, and for comparison also with pyrimidine nucleoside 5'-triphosphates (YTPs), i.e. CTP, UTP and TTP. The stabilities for the M(ATP)2- complexes are mostly larger than those for the corresponding M(YTP)2- species; this increased stability results from the metal ion back-binding to the base residue in M(ATP)2-, i.e. macrochelates are formed. Detailed analysis of the stability data allows calculation of the percentage of the closed form for the several M(ATP)2- complexes: back-binding is most pronounced in Cu(ATP)2- (67 +/- 2%), remarkable in Zn(ATP)2- (28 +/- 7%), and not observable for Ca(ATP)2- (2 +/- 6%). Comparison of these results with those from 1H-NMR and ultraviolet spectrophotometric studies allows the conclusion that two types of base back-bound macrochelates are formed: one with a direct, i.e. innersphere, M2+/N-7 coordination, and one with a water molecule between the metal ion and N-7, i.e. an outersphere interaction occurs [e.g. to about 10% in Mg(ATP)2-] through hydrogen bonding of a coordinated water to N-7. The formation degree of both forms of these closed isomers is quantified. The biological implications of these results are indicated and the versatility of ATP as a ligand is discussed by summarizing pertinent examples.

Adenosine Triphosphate↗
PubMed1987

Self-association and protonation of adenosine 5'-monophosphate in comparison with its 2'- and 3'-analogues and tubercidin 5'-monophosphate (7-deaza-AMP).

The concentration dependence of the chemical shifts of the protons H-2, H-8 and H-1' for 2'-, 3'- and 5'-AMP2- and of the protons H-2, H-7, H-8 and H-1' for tubercidin 5'-monophosphate (= 7-deaza-AMP2-; TuMP2-) has been measured in D2O at 27 degrees C to elucidate the self-association of the nucleoside monophosphates (NMPs). The results are consistent with the isodesmic model of indefinite non-cooperative stacking; the association constants for all four NMPs are very similar: K approximately 2 M-1. These 1H-NMR measurements and those on the dependence of the chemical shifts on the pD of the solutions indicate that the NMP2- species exist predominately in the anti conformation. Comparison of the shift data for 5'-TuMP and 5'-AMP shows that no hydrogen bonding between N-7 and -PO3H- occurs; hence, the previously observed and confirmed 'wrongway' chemical shift [Martin, R. B. (1985) Acc. Chem. Res 18, 32] connected with the deprotonation of the -PO3H- group most probably results from the anisotropic properties of the phosphate group which is in the anti conformation close to N-7. From the dependence between the chemical shift and the pD of the solutions the acidity constants were calculated for the four protonated NMPs, and for adenosine and D-ribose 5'-monophosphate. The measurements also allow an estimation of the first acidity constant of H3(5'-AMP)+ (pKDD3(AMP) = 0.9 and pKHH3(AMP) = 0.4). The values for pKHH2(NMP) and pKHH(NMP) were also determined from potentiometric pH titrations in aqueous solution (I = 0.1 M, NaNO3; 25 degrees C). The agreement of the results obtained by the two methods is excellent. The position of the phosphate group at the ribose moiety and the presence of N-7 in the base moiety influence somewhat the acid-base properties of the mentioned NMPs. Measurements with 5'-AMP in 50% (v/v) aqueous dioxane show that lowering of the solvent polarity facilitates removal of the proton from the H+(N-1) site while the -PO2-3 group becomes more basic; this increases the pH range in which the monoprotonated H(5'-AMP)- species is stable and which is now also extended into the physiological pH region. Some consequences of this observation for biological systems are indicated.

Adenine Nucleotides↗
PubMed1987

Self-association of adenosine 5'-monophosphate (5'-AMP) as a function of pH and in comparison with adenosine, 2'-AMP and 3'-AMP.

The concentration dependence of the chemical shifts for protons H-2, H-8, and H-1' of adenosine (Ado), 2'-AMP, 3'-AMP and 5'-AMP was measured in D2O at 27 degrees C under several degrees of protonation. All results are consistent with the isodesmic model of indefinite noncooperative stacking. The association constants for Ado decrease with increasing protonation: Ado (K = 15 M-1) greater than D(Ado)+/Ado (6.0 M-1) greater than D(Ado)+ (0.9 M-1). In contrast, a maximum is observed with 5'-AMP: 5'-AMP2- (K = 2.1 M-1) less than D(5'-AMP)- (3.4 M-1) less than D2(5'-AMP) +/- /D(5'-AMP)- (5.6 M-1) greater than D2(5'-AMP) +/- (approximately 2 M-1) greater than D3(5'-AMP)+ (less than or equal to 1 M-1). Self-stacking is most pronounced here if 50% of the adenine residues are protonated at N-1; complete base protonation reduces the stacking tendency drastically. Comparing the self-association of 2'-, 3'- and 5'-AMP shows that there is no influence of the phosphate-group position in the 2-fold negatively charged species, i.e., K congruent to 2 M-1 for all three AMP2- species. More importantly, there is also no significant influence observed if the stacking tendency of the three D2(AMP) +/- /D(AMP)-1:1 mixtures is compared (K congruent to 6-7 M-1); moreover, the measured association constants are within experimental error identical with the constant determined for D(Ado)+/Ado (K = 6.0 M-1). This indicates that any coulombic contribution between the -PO3(H)- group and the H+ (N-1) unit of the adenine residue to the stability of the mentioned stacks in D2O is small. However, experiments in 50% (v/v) dioxane-D8/D2O with the D2(5'-AMP) +/- /D(5'-AMP)- 1:1 system reveal, despite its low solubility, that coulombic interactions contribute to the self-association in an environment with a reduced polarity (compared to that of water). The implications of these observations for biological systems are briefly indicated.

Adenosine↗
PubMed1986

Self-association of 1,N6-ethenoadenosine 5'-triphosphate (epsilon-ATP) and promotion by metal ions.

The concentration dependence of the chemical shifts of the protons H-2, H-8, H-10, H-11, and H-1' of 1,N6-ethenoadenosine 5'-triphosphate (epsilon-ATP4-) has been measured in D2O at 27 degrees C to elucidate the self-association. The results are consistent with the isodesmic model of indefinite noncooperative stacking; the association constant, K = 1.9 +/- 0.2 M-1, is only slightly larger than the value for ATP4-, K = 1.3 +/- 0.2 M-1. The self-stacking tendency of epsilon-ATP4- is promoted by a factor of about 4 by (1:1) coordination of Mg2+ to the phosphate moieties, which probably links these together and also neutralizes part of the negative charge; Zn2+ is only about half as effective as Mg2+ in promoting the self-association. This result contrasts with the self-stacking properties of Mg(ATP)2- and Zn(ATP)2-, Zn2+ being considerably more effective in a 1:1 ATP system. It is assumed that due to the enhanced affinity of the N-6/N-7 site of the epsilon-adenine moiety towards Zn2+ repulsion of the bases occurs resulting thus in a lower stacking tendency; in addition, the simple isodesmic model is no longer applicable to the Zn(epsilon-ATP)2- system: to explain the experimental data, the formation of an intermolecular metal ion bridge in the dimeric stacks is proposed. The experimental conditions required for studies of the properties of monomeric epsilon-ATP systems are described. Care should be exercised in employing epsilon-ATP as a probe for ATP.

Adenosine Triphosphate↗
PubMed1986

Anomalous intrapulmonal vein drainage and pulmonary vein connection in DSA.

Anomalous pulmonary venous drainage can be detected and evaluated by angiographic studies. Now that intravenous DSA is available, this method can be used to demonstrate pulmonary venous return. This study presents the results of DSA examination in three patients having anomalous pulmonary vein connection with the left innominate vein and the superior vena cava respectively. In a fourth patient, intra-pulmonary atypical venous return could be demonstrated by DSA without anomalous connection. This minimal invasive procedure is diagnostically useful in anomalies of pulmonary veins when recommended post-processing techniques are evaluated, particularly in patients with additional cardiac septal defects.

Adult↗