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M Steinmetz

Publications and source records attributed to M Steinmetz.

At least 19 recordsLinked to original sources

[understanding and radiation hygiene assessment of solar UV exposure in Germany].

In order to monitor the natural ultraviolet (UV) radiation and to assess it from the point of view of radiation hygiene, the Federal Office for Radiation Protection (BfS) and the Federal Environmental Agency (UBA) have built up a common network for UV monitoring. Since 1993, the ground-level solar UV radiation has been measured at four sites in Germany every 6 minutes, with spectroradiometers in the wavelength range between 290 and 400 nm. Because erythema (sunborn) is of special interest in terms of radiation hygiene, the erythemal weighted irradiance was used as a measure for the biological effect of UV exposure. For this purpose, the measured spectral irradiance was multiplied by the relative erythemal weighting function, and the resulting function integrated from 290 to 400 nm. In the summer months of June and July 1999, the erythemal irradiance exceeded regularly the value of 175 mW/m2 in the south of Germany. In the north, values of not less than 160 mW/m2 were measured during this period. These values correspond to an UV index of more than 7 or 6, respectively--a high exposure regarding to the classification of the German Radiation Protection Commission (SSK), for which (absolute) sun protection is recommend. Between 1995 and 1999, the four sites were characterized by a small increase of the ground-level UV exposure of approx. 10%. Nevertheless, in consideration of the manifold factors affecting the acquired data, the measuring period of 5 years is still insufficient to demonstrate an ozone-dependent effect.

Erythema↗

Regulation of the renal basolateral transport system for organic anions by calcium channel blockers.

Calcium channel blockers have been reported to exert multiple effects on renal tubular function. Therefore, the effects of the calcium channel blockers nifedipine and verapamil on the cellular uptake of tritiated para -aminohippuric acid (PAH) into microdissected non-perfused rabbit kidney S2 proximal tubule segments were investigated to study a possible influence of calcium channel blockers on renal PAH transport. Since the tubules were entirely collapsed, the accumulated radioactivity overwhelmingly reflects the transport across the basolateral membrane. Tubular PAH accumulation was increased by 1 and 10 microm verapamil, and by 1 microm nifedipine, but it was unaffected by lower or higher concentrations of these calcium channel blockers. The increase in PAH accumulation caused by 1 microm nifedipine or 10 microm verapamil was independent from changes in intracellular Ca(2+) and inhibited by staurosporine (1 and 10 n m) a potent inhibitor of protein kinase C (PKC). Our results indicate that the calcium channel blockers nifedipine and verapamil increase the transport of organic anions across the basolateral membrane of proximal tubules, probably by an activation of PKC. Furthermore, the increased tubular PAH transport may disturb the estimation of the renal PAH-clearance.

Adenosine Triphosphate↗

Influence of purinoceptor antagonism on diadenosine pentaphosphate-induced hypotension in anesthetized rats.

Diadenosine polyphosphates (ApnA; n = 3-6) are potent vasoactive agents in isolated vessels. Information on effects of ApnA in vivo is still limited despite the fact that these compounds are starting to be used in humans. This study was designed to compare the effects of ApnA and their possible metabolites on blood pressure in vivo and to functionally identify purinoceptors involved in their action. All four ApnA and their degradation products induced a sustained drop of mean arterial blood pressure during i.v. infusion, which was fully reversible. The rank order of potency was Ap4A > or = Ap6A > Ap5A = Ap3A = ATP = ADP > AMP > or = adenosine, suggesting that the hypotensive effect is predominantly evoked by the original dinucleotides and not by their degradation products. The hypotensive effect of Ap5A was reduced by the P2X and P2Y(1) purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, the A(1) purinoceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, and the A(2) purinoceptor antagonist 3, 7-dimethyl-1-propargylxanthine. The hypertensive effect by the prototype P2X receptor agonist alphabeta-methylene ATP was inhibited by pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, too. Purinoceptor antagonists reduced the maximal effects of the agonists indicating a noncompetitive inhibition. In summary, the reported vasocontractile effect of ApnA seems to be limited to isolated preparations under resting tone conditions; however, the systemic cardiovascular effects of all four ApnA are hypotensive, also making them candidates for blood pressure reduction in humans. These effects are fast in onset and easily reversible. Activation of different purinoceptors in the vasculature (most probably P2Y(1) and A(2) receptors) contributes to the Ap5A-induced decrease of mean arterial blood pressure.

Animals↗

Diadenosine polyphosphates cause contraction and relaxation in isolated rat resistance arteries.

The effects of diadenosine polyphosphates (APnA; n = 3-6) and adenine nucleotides on contractile reactivity of isolated rat mesenteric resistance arteries (MrA) and superior epigastric arteries (SEA), which display a dense and sparse autonomic innervation, respectively, were evaluated. All agonists examined, except adenosine and AMP, induced contractions. The rank order of potency was similar in both arteries: alpha,beta-methylene ATP (alpha,beta-meATP) > AP5A > AP6A > AP4A > ATP > ADP > AP3A. Contractions were stable during several minutes in SEA but highly transient in MrA. They were reduced after exposure to 10 microM alpha,beta-meATP and by 10 microM of the P2X antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid. During phenylephrine (10 microM)-induced contractions, the agonists induced a further contraction in SEA. In MrA, however, further contraction was followed by marked relaxation. The rank order of relaxing potency was comparable to that of the contractile potency of agonists. Also, the relaxing effects of APnA were blunted by 10 microM pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid and after exposure to alpha,beta-meATP. In vitro and in vivo sympathectomy with 6-hydroxydopamine and removal of the endothelium did not modify the effects of APnA in MrA. Thus, the contractile effects of APnA in resistance arteries 1) are due to a P2X purinoceptor-mediated stimulation of the smooth muscle; 2) depend on the length of the phosphate chain; and 3) are followed by endothelium-independent relaxing effects in MrA but not SEA, which may involve receptors that are similar to those mediating contraction. The regional heterogeneity of APnA effects cannot be attributed to a direct neurogenic influence.

Adenine Nucleotides↗

Heterogenous vascular effects of AP5A in different rat resistance arteries are due to heterogenous distribution of P2X and P2Y(1) purinoceptors.

In the accompanying article, we showed that AP5A displayed heterogenous vasoactive effects in rat resistance arteries. It induced a stable vasoconstriction in the superior epigastric artery (SEA) and a transient vasoconstriction in the mesenteric resistance artery (MrA). In the phenylephrine-precontracted MrA AP5A induced a marked vasorelaxation. In this study the noncompetitive inhibition of the AP5A-induced vasoconstriction with pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid was found to be significantly stronger in MrA than in SEA. The nonselective P2 purinoceptor antagonist suramin inhibited AP5A-induced vasoconstriction in MrA only. The vasoconstriction by the P2X purinoceptor agonist alpha,beta-methylene ATP was inhibited by with pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid and suramin similarly to that induced by AP5A. Thus, the AP5A-induced vasoconstriction is due to P2X receptor activation, but two different P2X receptors seem to be operational in the two different vessels. The AP5A-induced vasorelaxation of phenylephrine-precontracted MrA was inhibited by the P2Y(1) receptor antagonist ADP3'5'. The vasorelaxation induced by ADPbetaS (P2Y(1) agonist) also was inhibited by ADP3'5'. These findings suggest that AP5A-induced vasorelaxation of MrA is caused by P2Y(1) receptor activation. The P1 (A(2)) receptor antagonist 3, 7-dimethyl-1-propargylxanthine only slightly inhibited AP5A-induced vasorelaxation at high concentrations. Adenosine and the A(2) receptor agonist CGS21680 failed to produce significant vasorelaxation. Therefore, vasorelaxation in MrA does not involve A(2) purinoceptor activation. AP5A-induced vasorelaxation was not inhibited by Ca(2+)- or ATP-dependent K(+) channel blockade with clotrimazole, apamin, or glibenclamide. These data indicate that vasoconstriction in MrA and SEA by AP5A is due to different P2X receptors, and vasorelaxation in precontracted MrA is due to P2Y(1) receptor activation.

Animals↗

Kidney transplantation improves baroreceptor sensitivity.

Kidney transplant recipients as well as patients on hemodialysis frequently share an increased risk of cardiovascular diseases. Besides other factors, modulations in central neural blood pressure regulation have to be considered as a pathogenetic factor. In this study, baroreceptor function as a possible modulator of blood pressure and the activity of the generating components of the sympathetic nervous system were estimated in 20 kidney transplant recipients, 20 normotensive patients on hemodialysis and 20 age-matched volunteers using the sequence analysis technique and Fast Fourier Transformation (FFT). No blood pressure differences could be measured (83.7+/-2.5 vs. 82.5+/-3.8 vs. 79.2+/-2.4 mm Hg). Pulse interval-blood pressure sequences and the slope of delta pulse interval/delta mean arterial blood pressure of these sequences, representing baroreceptor sensitivity, did not differ between kidney transplant recipients and controls (11.2+/-1.4 vs. 13.4+/-1.3 ms/mm Hg), whereas in hemodialysis patients a reduced baroreceptor sensitivity (5.2+/-1.2 ms/mm Hg) was detected. The 66-129 mHz component (Mayer waves) of heart rate and blood pressure spectrum in normals (650+/-57 and 630+/-70 modulus) significantly (p<0.05) exceeded its equivalent in kidney transplant recipients (430+/-32 and 452+/-27 modulus) and patients on hemodialysis (375+/-38 and 394+/-40 modulus). In conclusion, our study provided evidence that both in kidney transplant and dialysis patients a decreased activity of the generating compounds of the sympathetic nervous system can be detected as compared to healthy volunteers. In contrast to hemodialysis patients, the baroreceptor sensitivity is unaffected in kidney transplant recipients and may, therefore, not contribute to the development of cardiovascular diseases.

Adult↗

Effects of moxonidine and clonidine on potassium excretion in Sprague-Dawley rats.

Recently we demonstrated that clonidine and moxonidine exert specific action on fractional fluid and Na+ excretion in anaesthetised Sprague-Dawley rats. Classically, most of the diuretics used induce an increased K+ excretion, at least in part due to Na+ load in the distal tubule and exchange of Na+ by K+. Therefore, we studied the effects of moxonidine and clonidine on K+ excretion in anaesthetised Sprague-Dawley rats. Moxonidine (0.25 and 0.5 mg kg-1 body wt. i.v.) increased transiently K+ (1.0 +/- 0.3 -1.9 +/- 0.4 and 0.9 +/- 0.2 -2.9 +0.7 micromol min-1 100 g body wt.) and Na+ (1.4 +/- 1.0 -6. 9 +/- 3.1 and 0.8 +/- 0.36 -6.6 +/- 1.5 micromol min-1100 g body wt.) excretion. Clonidine (0.25 mg kg-1) caused a more pronounced increase in K+ (1.0 +/- 0.1 -2.7 +/- 0.4 micromol min-1 100 g body wt.) and Na+ (0.6 +/- 0.3 -9.5 +/- 0.4 micromol min-1 100 g body wt.) excretion, whereas the higher dose of 0.5 mg kg-1 body wt. had less effect as compared to moxonidine (K+: 0.8 +/- 0.1 -1.7 +/- 0.2 micromol min-1 100 g body wt., Na+: 0.3 +/- 0.1 -3.4 +/- 1.0 micromol min-1 100 g body wt.). The increased electrolyte excretion returned (similar to moxonidine) to baseline levels within 20 min after injection of the drugs. Antagonists such as idazoxan and yohimbine did not change K+ and Na+ excretion by their own. Both, the non-selective imidazoline/alpha2-adrenoceptor antagonist idazoxan and the pure alpha2-adrenoceptor antagonist yohimbine attenuated the moxonidin-induced effects on K+ and Na+ excretion. This could be also observed with clonidine and simultaneous injection of these two antagonists. Our results demonstrate that moxonidine and clonidine also increase renal K+ excretion in this animal model. K+and Na+ excretion show a parallel behaviour, indicating that the increased K+ excretion is mainly due to Na+ load in the tubular system.

Adrenergic alpha-2 Receptor Agonists↗

Short-term and long-term hemodynamic and clinical effects of metoprolol alone and combined with amlodipine in patients with chronic heart failure.

BACKGROUND: Initiation of beta-blocker therapy is often limited by worsening congestive heart failure, which may manifest as worsening hemodynamics. Deleterious hemodynamic effects might be mitigated with the vasodilation of combined calcium channel/beta-blocker therapy. METHODS AND RESULTS: This prospective, randomized study assessed the safety and efficacy of metoprolol alone or combined with amlodipine on hemodynamic parameters at baseline, 2 hours after the first dose of study medication, and after 12 weeks of therapy in patients receiving background triple therapy for mild to severe heart failure. Functional, exercise, and hormonal status were assessed at baseline and end of study. Twenty-nine patients (mean age 50 +/- 12.1 years) were enrolled; 21 completed 12 weeks of treatment. Mean ejection fraction at baseline was 13.4% +/- 5.7%; 79% of patients had heart failure classified as New York Heart Association class III, and 66% had heart failure of idiopathic origin. Heart rate and blood pressure did not change with short-term therapy in either group. The first dose of both regimens produced significant increases in systemic vascular resistance and significant decreases in cardiac output and index and stroke volume and stroke work indexes; combination therapy acutely yielded small but statistically significant increases in pulmonary artery, pulmonary capillary wedge, and right atrial pressures. Long-term therapy with both regimens produced significant decreases in heart rate, systemic vascular resistance, and pulmonary capillary wedge pressure and significant increases in cardiac output and index and stroke volume and stroke work indexes. Combination therapy produced significant long-term decreases in blood pressure. CONCLUSIONS: There was no further measurable benefit with the addition of amlodipine to metoprolol compared with the effects of metoprolol alone. Therapy with metoprolol alone and the combination of metoprolol and amlodipine was well tolerated in patients with mild to severe heart failure, as evidenced by a lack of adverse effects on hemodynamic parameters over the short term and clinical and hemodynamic improvement with long-term treatment.

Adrenergic beta-Antagonists↗

Peptidomimetic compounds that inhibit antigen presentation by autoimmune disease-associated class II major histocompatibility molecules.

We have identified a heptapeptide with high affinity to rheumatoid arthritis-associated class II major histocompatibility (MHC) molecules. Using a model of its interaction with the class II binding site, a variety of mimetic substitutions were introduced into the peptide. Several unnatural amino acids and dipeptide mimetics were found to be appropriate substituents and could be combined into compounds with binding affinities comparable to that of the original peptide. Compounds were designed that were several hundred-fold to more than a thousand-fold more potent than the original peptide in inhibiting T-cell responses to processed protein antigens presented by the target MHC molecules. Peptidomimetic compounds of this type could find therapeutic use as MHC-selective antagonists of antigen presentation in the treatment of autoimmune diseases.

Amino Acid Sequence↗

Vertex epidural hematoma: surgical versus conservative management: two case reports and review of the literature.

OBJECTIVE AND IMPORTANCE: Vertex epidural hematomas may be underestimated or overlooked altogether when computed tomographic scans alone are used for diagnosis. Such hematomas can be resolved with active intervention and sometimes with conservative treatment. CLINICAL PRESENTATION: Two cases of successfully treated vertex epidural hematomas, in a 33-year-old man who presented with seizures and an 11-year-old girl who presented with headache and vomiting, are described. Both hematomas were traumatic in origin and were associated with cranial fractures. In each, coronal images (computed tomographic or magnetic resonance imaging scans) showed the extent of the hematoma much more clearly than did axial images. INTERVENTION: One case was treated surgically and the other conservatively. CONCLUSION: Magnetic resonance imaging is not usually indicated for trauma patients, but it is an appropriate diagnostic modality for these rare lesions, to supplement standard axial computed tomographic scans. Because vertex epidural hematomas may resolve spontaneously with time, conservative treatment should be considered on a case-by-case basis.

Adult↗

Activation of Na+, H+ exchanger produces vasoconstriction of renal resistance vessels.

To evaluate the influence of the sodium/proton exchanger (Na+,H+ exchanger) on the constriction of rat resistance vessels and on the iliac artery, the isometric vasoconstrictions of renal resistance vessels and strips from iliac artery derived from Wistar-Kyoto rats were measured using a vessel myograph. The Na+,H+ exchanger was activated by intracellular acidification using propionic acid. Cytosolic pH (pHi) and cytosolic free sodium concentration ([Na+]i) in vascular smooth muscle cells were measured using the fluorescent dye technique. The activation of the Na+,H+ exchanger increased the [Na+]i by 12.4 +/- 1.3 mmol/L (n = 8). The activation of the Na+,H+ exchanger caused a contractile response of the renal resistance vessels (increase of tension, 1.5 +/- 0.1 x 10(-3) N; n = 13) and of the rat iliac artery (increase of tension, 7.5 +/- 0.8 x 10(-3) N; n = 5). The contractile response after activation of the Na+,H+ exchanger was significantly inhibited in the absence of external sodium or in the presence of amiloride, confirming the involvement of the Na+,H+ exchanger. The contractile response after activation of the Na+,H+ exchanger was significantly reduced in the absence of external calcium, after inhibition of calcium channels by nifedipine, and in the presence of an intracellular calcium antagonist 8-(diethylamino-)-octyl-3,4,5-trimethoxybenzoate (TMB-8), indicating that the activation of the Na+,H+ exchanger consecutively caused transplasma membrane calcium influx. On the other hand, the inhibition of the Na+,Ca2+ exchanger by NiCl2 significantly increased the vasoconstriction of renal resistance vessels after activation of the Na+,H+ exchanger. The activation of the Na+,H+ exchanger produces vasoconstriction by an increased cytosolic sodium concentration, inhibition of the Na+,Ca2+ exchanger, and activation of transplasma membrane calcium influx through potential dependent calcium channels.

Acids↗

Resting diastolic function and left ventricular mass are related to exercise capacity in hypertensive men but not in women.

We evaluated the impact of diastolic function and gender on exercise capacity in sedentary, untreated hypertensive subjects (34 men, 23 women) using echocardiography and a bicycle ergometry with measurement of oxygen consumption (VO2). In men, peak (A) mitral inflow velocity and left ventricular (LV) mass were inversely related to peak VO2 (r = -0.64) and maximal workload (r = -0.57) and were the sole independent determinants of exercise capacity. In women, there was no relationship between any echocardiographic measure and exercise capacity. Thus, LV mass and Doppler-determined diastolic function predict maximal VO2 in hypertensive men but not in women. This finding may be related to gender differences in the contribution of diastolic filling to exercise capacity or may reflect limitations of resting Doppler echocardiography to predict exercise diastolic filling in hypertensive women.

Adult↗

From genetic to structural characterization of a new class of RNA-binding domain within the SacY/BglG family of antiterminator proteins.

SacY is the prototype of a family of regulatory proteins able to prevent transcription termination. It interacts with a 29 nucleotide RNA sequence able to fold into a stem-loop structure and partially overlapping with a terminator sequence located in the 5' leader mRNA region of the gene it controls. We show here that the N-terminal fragment of SacY, SacY(1-55), and the corresponding fragments of other members of the family have antiterminator activities with efficiency and specificity identical to those of the full-length proteins. In vitro, this activity correlates with the specific affinity of SacY(1-55) for its RNA target. UV melting experiments demonstrate that SacY(1-55) binding stabilizes the RNA target structure. The NMR solution structure of SacY(1-55) is very similar to that obtained in the crystal (van Tilbeurgh et al., 1997): the peptide is folded as a symmetrical dimer without any structural homology with other RNA-binding domains yet characterized. According to a preliminary NMR analysis of the SacY(1-55)-RNA complex, the protein dimer is not disrupted upon RNA binding and several residues implicated in RNA recognition are located at the edge of the dimer interface. This suggests a new mode of protein-RNA interaction.

Amino Acid Sequence↗

Continuous solar UV monitoring in Germany.

Early in 1993, the Federal Office for Radiation Protection (BfS, Salzgitter) together with the Federal Environmental Office (UBA, Berlin) established an overall UV monitoring network for the continuous measurement of spectrally resolved UV radiation. Every 6 min the solar UV spectrum is measured by a Bentham DM 150 double monochromator system in a wavelength ranging from 290 to 450 nm. Every night, UV data are automatically transferred via modem to the reference station in Munich where they are quality controlled and then stored in a host computer. Human health assessment of the exposure is documented in 1/2 h MED (minimal erythemal dose) values. The selected sites of Zingst (1 m, 54 degrees N, Baltic Sea), Offenbach (110 m, 50 degrees N, Rhine rift valley), Schauinsland (1205 m, 48 degrees N, Black Forest) and Neuherberg (493 m, 48 degrees N, Munich) provide a good overview of the UV radiation situation in Germany and therefore an ideal supplement to more detailed biological effect research, especially of comparison measurements with biosensors under environmental conditions. Preliminary investigations have already been started.

Germany↗