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.

The self-association of flavin mononucleotide (FMN(2-)) as determined by (1)H NMR shift measurements.

The concentration dependence of the (1)H NMR chemical upfield shifts of the protons H6, H9, H7alpha, and H8alpha of the 7,8-dimethylisoalloxazine residue of flavin mononucleotide (FMN(2-)) has been measured and the self-stacking tendency of FMN(2-) was quantified with the isodesmic model of indefinite non-cooperative self-association. The stacking tendency of FMN(2-) is considerable and described in the concentration range of 0.0025-0.1 M with the indicated model by K = 27 +/- 15 M(-1) (25 degrees C; I = 0.1-0.3 M). This result is compared with related ones from the literature. The caveats regarding the self-stacking properties of FMN(2-) and their dependence on the concentration are discussed.

Metal ion-carbonyl oxygen recognition in complexes of acetyl phosphate.

Studies on acetyl phosphate (AcP2-), one of the so-called 'energy-rich' mixed-acid anhydrides, are summarized. Based on stability constants determined by potentiometric pH titrations in aqueous solution, it is shown that the M(AcP) complexes of Ca2+, Mg2+, Mn2+, Cu2+, and Zn2+ are more stable than is expected from the basicity of the phosphate group of AcP2-. This observed stability increase is attributed to an additional interaction of the already phosphate-coordinated metal ion (M2+) with the carbonyl oxygen of the anhydride unit. These conclusions are corroborated by the properties of the complexes of the hydrolysis-stable acetonylphosphonate (AnP2-). The formation degrees of the various six-membered chelates occurring in the M(AcP) and M(AnP) systems are presented and evidence is given that these chelates persist in mixed ligand complexes and that their formation degree is promoted by a low solvent polarity. The biological relevance of these results regarding carbonyl oxygen-metal ion interactions is briefly indicated.

Evaluation of intramolecular equilibria in complexes formed between substituted imidazole ligands and nickel (II), copper (II) or zinc (II).

The metal ion-binding properties of imidazole-4-acetate (ImA-), 4(5)-aminoimidazole-5(4)-carboxamide (AImC), 2,2'biimidazole(BiIm) (I. Török et al., J. Inorg. Biochem. 71 (1998) 7-14), and bis (imidazol-2-yl)methane(BiImM) (K. Várnagy et al., J. Chem. Soc., Dalton Trans. (1994) 2939-2945) have been evaluated by using the recently published stability constants and by applying the recently established log K(ML)M versus pK(HL)H straight-line plots (L. E. Kapinos et al., Inorg. Chim. Acta 280 (1998) 50-56) which hold for simple imidazole-type ligands. The indicated analysis regarding the intramolecular equilibrium between a monodentatally imidazole-nitrogen-coordinated (open) species and a chelated isomer provides helpful insights, e.g., the formation degree of chelates is more favored if six-membered rings can be formed, as in the case with M(BiImM)2+ compared to M(BiIm)2+, though in both instances the formation degree of the chelates is large. The formation degree of chelates in the M(ImA)+ complexes increases in the series Zn(ImA)+ (87%)

Intramolecular stacking interactions in ternary copper(II) complexes formed with 2,2'-bipyridine or 1,10-phenanthroline and 9-(4-phosphonobutyl)adenine (dPMEA), the carba relative of the antiviral nucleotide analogue 9.

The stability constants of the mixed ligand complexes formed between Cu(Arm)2+, where Arm=2,2'-bipyridine (Bpy) or 1,10-phenanthroline (Phen), and the monoanion or the dianion of 9-(4-phosphonobutyl)adenine (dPMEA=3'-deoxa-PMEA), which is the carba analogue of the antivirally active 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), were determined by potentiometric pH titrations in aqueous solution at 25 degrees C and I=0.1 M (NaNO3). Detailed stability constant comparisons reveal that in the monoprotonated ternary Cu(Arm)(H;dPMEA)+ complexes the proton is at the phosphonate group and that stacking between Cu(Arm)2+ and H(dPMEA)- plays a significant role. For the Cu(Arm)(dPMEA) complexes a large increase in complex stability (compared to the stability expected on the basis of the basicity of the phosphonate group) is observed, which is due to intramolecular stack formation between the aromatic ring systems of Phen or Bpy and the purine moiety of dPMEA2-. The formation degree of the stacked isomer in the Cu(Arm)(dPMEA) systems is on the order of 90%, though it is somewhat more pronounced with Phen than with Bpy. Comparisons of the Cu(Arm)(N) systems, where N=dPMEA2- and PMEA2- or adenosine 5'-monophosphate (AMP2-), reveal that the stacking properties of dPMEA2- and PMEA2-resemble closely those of their parent nucleotide AMP2-.

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.

[Radionuclide ventriculography. I. Fundamentals and methods (author's transl)]. / Radionuklid- Ventrikulographie. I. Grundlagen und Methoden.

Using local time activity curves parameters are calculated which depend on the local wall motion of the heart cavities. These functional parameters allow the determination of the contours of the heart cavities and the assessment of segmental wall motion disorders. The left ventricular ejection fraction has been calculated by enddiastolic and endsystolic counts using a method which takes into account background inhomogeneity.

[Radionuclide ventriculography. III. Clinical results--parameters of regional wall motility (author's transl)]. / Radionuklid- Ventrikulographie. III. Klinische Ergebnisse: Parameter der regionalen Wandbewegung.

Radionuclide ventriculography and cineangiography were performed in 62 patients with suspected coronary artery disease. Regional wall motility irregularities could be demonstrated in 97% of those patients who revealed an irregularity in the cineangiogram. Two small scars of the posterior myocardial wall escaped detection. The sensitivity of the radionuclide ventriculography was 97%, the specificity was 80%, 4 patients with normal cineangiography showed small irregularities in the radionuclide ventriculogram. 70 patients with infarction revealed wall motility irregularities in 90%, whereas perfusion defects could be detected by thallium scintigraphy in 66% (young and old infarctions).

[Radionuclide ventriculography. II. Clinical results--parameters of global ventricular function (author's transl)]. / Radionuklid- Ventrikulographie. II. Klinische Ergebnisse: Parameter der globalen Ventrikelfunktion.

The ejection fraction as determined by gated blood pool studies was compared with the ejection fraction as evaluated by the following conventional methods: 1) biplane cineangiography employing the Simpson rule. Correlation was r = 0.805 (n = 25); 2) the same patients using the area-length method (r = 0.88, n = 25); 3) monoplane cineangiography using the method of Greene et al. (5) (r = 0.86, n = 35). In 20 patients the maximal contraction velocity as evaluated by radionuclide ventriculography was compared with the mean systolic ejection rate. The observed correlation was weak (r = 0.62, n = 20); however, it should be noted that the radionuclide method determines the maximum contraction velocity whereas cinceangiography measures an average value over the whole systole.

[Assessment of left ventricular regional function by means of radioactive isotopes (author's transl)]. / Bestimmung der Regionalfunktion des linken Ventrikels mit Hilfe von radioaktiven Isotopen.

Extensive analysis of heart function by scintigraphy yields global parameters of ventricular volumes and their changes during the heart cycle (ejection fraction, enddiastolic and endsystolic volumes, velocity of contraction and relaxation). Additionally, information regarding localized disorders of wall motion may be obtained in a qualitative and quantitative manner by the parameters "phase" and "amplitude". These parameters can be computed from regional time-activity curves by Fourier analysis. The radionuclide ventriculogram at rest is suitable for the detection and follow-up of asynergies caused by acute and chronic infarction. In can also be used as a method of distinguishing between reversible and irreversible asynergy by therapeutical intervention (intervention ventriculography). Abnormalities of regional wall motion which develop during exercise may indicate hemodynamically relevant coronary artery stenoses.

Evaluation of aortic and mitral valve regurgitation by radionuclide ventriculography: comparison with the method of Sandler and Dodge.

The present investigation was undertaken to introduce a quantitative scintigraphic method for evaluation of regurgitation and to compare it with the generally accepted quantitative method of Sandler and Dodge (Sandler et al., 1963). Radionuclide ventriculography was carried out after injection of 20 mCi 99mtechnetium-labeled red blood cells. Time-activity curves were obtained from the left and right ventricular regions. The ratio (A) of end-diastolic-end-systolic count-rate differences for the left and right ventricles was calculated. The ratio (A) was compared with a hemodynamic ratio (Ah) determined after the method of Sandler and Dodge (1963) with the stroke volume of the left ventricle measured angiographically, and the stroke volume of the right ventricle measured by thermodilution. In 33 patients with aortic and mitral valve regurgitation we found a correlation of r = 0.75 between (A) and Ah). Due to a broad range of normal values of (A) the sensitivity of the scintigraphic method is low. The specificity seems to be high, however, since in 64 patients with all types of heart diseases there were no false positive results. Comparing the described scintigraphic method with other modern or generally accepted methods, the principal advantages are noninvasiveness, good practicability, and the fact that important additional information about the functional state of the heart is gained. This is important in follow-up studies in patients with chronic valvular incompetence. It seems that this method will become a valuable supplement to heart catheterization in the diagnosis of valvular heart disease and may partially replace invasive methods for measuring the regurgitation fraction.

Radionuclide ventriculography: a noninvasive method for the detection and quantification of left-to-right shunts in atrial septal defect.

The present investigation was undertaken to assess a new scintigraphic method for the diagnosis of left-to-right shunts due to atrial septal defect based on the differing stroke volumes of left and right ventricles and to compare it with oxymetric data. Radionuclide ventriculography was carried out after injection of 20 mCi 99mtechnetium-labeled red blood cells. Time-activity curves were obtained from the left and right ventricular regions, and the ratio (A) of end-diastolic-end-systolic count rate differences for the left and right ventricles was calculated. The left-to-right shunt (in percent of the pulmonary flow rate) is then given as 100 X (1 - A/1.43; 1.43 being the previously determined mean value of A in 66 normal patients. In 16 patients with an atrial septal defect and/or partial anomalous pulmonary venous connection a correlation of r = 0.81 was found between those shunts determined by the scintigraphic method and those calculated by oxymetric data. The specificity of the method and the sensitivity in detecting left-to-right shunts exceeding 30% are high. The method is practical and already widely used for determination of ejection fraction end-diastolic volume and other factors. The combination of this technique with other methods for shunt diagnosis such as gamma-fit analysis may prove of special value.

Self-association of nucleotides. Effects of protonation and metal ion coordination.

The self-association of nucleosides decreases within the series adenosine greater than guanosine greater than inosine greater than cytidine approximately uridine. The same trend is observed for the corresponding nucleotides, though less pronounced, as the charge effect governs series like adenosine much greater than AMP2- greater than ADP3- approximately greater than ATP4-. Protonation of adenosine considerably reduces its self-stacking tendency: this is different with ATP4-, where a maximum is reached for H2(ATP)2- caused by additional ionic interactions in the [H2(ATP)]2(4-) dimer. Metal ion coordination may promote self-association, e.g., of ATP4- via (mainly) charge neutralization (Mg2+) and the formation of intermolecular bridges in dimeric stacks (Zn2+, Cd2+). These results allow definition of conditions with negligible self-association and thus the determination of the stability and structure of monomeric nucleotide complexes in aqueous solution, e.g., quantification of macrochelate formation in M(ATP)2- complexes. Some biological implications of the results are indicated.

[A rare cause of myocarditis in a 30-year-old patient]. / Seltene Ursache einer Myokarditis bei einem 30-jährigen Patienten.

CASE REPORT: A 30-year-old male was admitted to hospital because of chest pain and raised cardiac enzymes. Coronary heart disease was excluded by coronary angiography. Assuming myocarditis serological testing was performed and showed markedly raised antibody titers against Coxiella Burnetii. We treated the patient with doxycycline, 2 times 100 mg daily for 5 months. CONCLUSION: Acute Q-fever should be considered as a possible cause of myocarditis, especially in rural areas.