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Biomedical subjects

M Sturm

Publications and source records attributed to M Sturm.

At least 19 recordsLinked to original sources
PubMed2005

Role of land-surface changes in arctic summer warming.

A major challenge in predicting Earth's future climate state is to understand feedbacks that alter greenhouse-gas forcing. Here we synthesize field data from arctic Alaska, showing that terrestrial changes in summer albedo contribute substantially to recent high-latitude warming trends. Pronounced terrestrial summer warming in arctic Alaska correlates with a lengthening of the snow-free season that has increased atmospheric heating locally by about 3 watts per square meter per decade (similar in magnitude to the regional heating expected over multiple decades from a doubling of atmospheric CO2). The continuation of current trends in shrub and tree expansion could further amplify this atmospheric heating by two to seven times.

Alaska↗
PubMed2004

Incidence and time course of intimal plaque formation in the right coronary artery after radiofrequency current application detected by intracoronary ultrasound.

BACKGROUND: Despite the current clinical use of radiofrequency (RF) catheter ablation in infants and children, the late effects of RF current application at immature myocardium remain unclear. The purpose of this study was to investigate incidence and time course of coronary lesions after RF current application at developing myocardium in an animal model. RESULTS: In 10 pigs, 6 weeks of age (13+/-2 kg), RF current (500 kHz) was delivered by temperature guidance (75 degrees C) using a steerable electrode catheter (4 mm tip electrode) over 30-second periods. RF lesions were created at the lateral right atrial wall at the tricuspid valve annulus and the lateral left atrial and ventricular wall at the mitral valve annulus. Subsequent coronary angiography and intracoronary ultrasound (ICUS) of the right coronary artery (RCA) and the left circumflex artery (CX) were performed 3, 6, 9 and 12 months after RF current application. Quantitative coronary angiography did not exhibit any significant stenosis of the vessels during the study period. Intimal lesions of the RCA were documented for the first time at the 6-month study in 3 animals by ICUS (mean plaque area 2.2+/-0.2 mm(2), mean area stenosis 30.4+/-4.0%). There was no significant change in lesion length, area stenosis and plaque area at the 9- and 12-month studies. All 3 coronary artery lesions were confirmed in close proximity to myocardial RF lesions by histological examination 12 months after RF delivery. No intimal plaque formation of the CX was observed. CONCLUSIONS: Affection of the RCA as a late sequel after RF current application at the lateral right atrial wall occurred in 3 out of 8 long-term surviving pigs. Three to six months seem to be the time frame for the development of intimal lesions after RF delivery. In this experimental setting, angiography failed to detect these intimal changes. The potential risk of coronary affection may be important for catheter ablation procedures at the right atrial myocardium in infants and small children.

Animals↗
PubMed2001

Climate change. Increasing shrub abundance in the Arctic.

The warming of the Alaskan Arctic during the past 150 years has accelerated over the last three decades and is expected to increase vegetation productivity in tundra if shrubs become more abundant; indeed, this transition may already be under way according to local plot studies and remote sensing. Here we present evidence for a widespread increase in shrub abundance over more than 320 km of Arctic landscape during the past 50 years, based on a comparison of historic and modern aerial photographs. This expansion will alter the partitioning of energy in summer and the trapping and distribution of snow in winter, as well as increasing the amount of carbon stored in a region that is believed to be a net source of carbon dioxide.

Arctic Regions↗
PubMed2001

Interleukin-2 inhibits glucocorticoid receptor transcriptional activity through a mechanism involving STAT5 (signal transducer and activator of transcription 5) but not AP-1.

Cytokines and glucocorticoids (GCs) signaling pathways interfere with each other in the regulation of apoptosis and gene expression in the immune system. Interleukin-2 (IL-2), through the Janus kinase/signal transducers and activators of transcription (Jak/STAT) and mitogen-activated protein kinase (MAPK) pathways, activates STAT5 and activated protein-1 (AP-1) transcription factors, respectively, which are known to repress glucocorticoid receptor (GR) activity, at least in part, through protein-protein interactions. In this work, we have analyzed the mechanisms whereby IL-2 down-regulates the GC-induced transactivation of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) in murine CTLL-2 T lymphocytes. Mutagenesis studies revealed that the MMTV-LTR STAT5 binding site (-923/-914) was not required for IL-2-mediated inhibition but identified both glucocorticoid response elements (GREs) and the -104/+1 region as critical elements for this negative response. The DNA binding activities of transcription factors required for GC-mediated activation of the MMTV-LTR promoter and that bind to the -104/+1 region (nuclear factor-1, Oct-1) were not affected by IL-2 treatment. Overexpression of wild-type STAT5B enhanced the effect of IL-2 on MMTV-LTR activity, and a dominant negative form of STAT5B (Y699F) abolished the IL-2-mediated MMTV-LTR inhibition, whereas AP-1 activation had no effect in this system. Direct interaction between liganded GR and STAT5 was observed in CTLL-2 cells in a STAT5 phosphorylation-independent manner. Overexpression of nuclear coactivators CBP (CREB-binding protein) or SRC-1a (steroid receptor coactivator 1a) did not blunt IL-2 inhibitory effects. We suggest that the STAT5-repressive activity on the GC-dependent transcription may involve direct interaction of STAT5 with GR, is dependent on the promoter context and STAT5 activation level, and occurs independently of coactivators levels in T cells.

Animals↗
PubMed2000

The glucocorticoid receptor and STAT6 physically and functionally interact in T-lymphocytes.

In lymphocytes, glucocorticoids (GC)- and interleukin-4-signaling pathways are known to interact, as evidenced by inhibition of IL-4-mediated proliferation by dexamethasone or suppression of GC-induced apoptosis by IL-4. In this study, we characterized the molecular basis for this reciprocal interference. We report that, in murine CTLL-2 cells, IL-4 inhibits GC-induced MMTV (mouse mammary tumor virus) promoter transactivation, and that GC suppress IL-4-induced transactivation of a STAT6 (signal transducers and activators of transcription 6)-responsive promoter without affecting IL-4-stimulated STAT6 DNA-binding. Moreover, we evidenced a physical association between GC receptor and STAT6, which proved to be functionally relevant, since STAT6 overexpression increased the IL-4 inhibitory effect on GC-induced MMTV transactivation.

Animals↗
PubMed2000

[Intracoronary ultrasound].

IVUS imaging provides a 2-dimensional, cross-sectional view into the lumen and vessel wall structure of coronary arteries; it is superior to angiography with regard to visualization about several aspects of coronary artery disease. IVUS has given important information on the development and progression of coronary atherosclerosis. Moreover, IVUS has improved our understanding of the mechanisms of percutaneous interventions and restenosis. IVUS-guided balloon sizing during PTCA may increase acute lumen gain as compared to conventional angiographic guidance. Optimization of stent implantation by IVUS guidance also results in larger initial lumen gain than with angiographic control; this approach, however, does not reduce restenosis rates. In summary, IVUS is an optional imaging modality that provides clinically useful information in selected patients.

Angioplasty, Balloon, Coronary↗
PubMed2000

Effects of intracardiac radiofrequency current application on coronary artery vessels in young pigs.

INTRODUCTION: Radiofrequency current is widely used in children to ablate accessory AV pathways. Previous data in a pig model demonstrated coronary artery obstruction adjacent to radiofrequency current lesions 48 hours and 6 months after energy delivery. In the present study, the long-term effects (>6 months) of radiofrequency current application on coronary artery vessels in young pigs are assessed. METHODS AND RESULTS: Radiofrequency current (500 kHz) was delivered over 30 seconds in ten piglets (mean body weight 12.8 kg) using a steerable 6-French catheter with a 4-mm thermistor tip electrode (target temperature 75 degrees C). Lesions were created under fluoroscopic and electrocardiographic guidance at the lateral right atrial (RA) wall above the tricuspid valve orifice, and at the lateral left atrial and left ventricular wall adjacent to the mitral valve orifice. Selective coronary angiography and intravascular ultrasound (IVUS) studies were performed 3, 6, 9, and 12 months after energy application. After 12 months, the lesions were studied pathohistologically. All lesions consisted of compact fibrous tissue. RA lesions extended to the adjacent right coronary artery and led to coronary artery involvement with increased fibrous tissue in the adventitia and media and intimal thickening in three animals. Coronary arterial narrowing was documented by IVUS during follow-up in all three cases 9 months after energy application. Angiography failed to demonstrate coronary pathology in any of the three animals. CONCLUSION: The risk of late coronary artery lesions must be considered when catheter ablation at the RA wall is planned in children with free-wall accessory AV pathways.

Animals↗
PubMed2000

Human ApoA-IV overexpression in transgenic mice induces cAMP-stimulated cholesterol efflux from J774 macrophages to whole serum.

The role of apolipoprotein A-IV (apoA-IV) in lipoprotein metabolism has not been established. The aim of the present study was to investigate the role of apoA-IV in reverse cholesterol transport by comparing cellular cholesterol efflux to serum or serum fractions from control mice and from mice transgenic for human apoA-IV (HuA-IVTg mice). When Fu5AH hepatoma cells were used, the cholesterol efflux to serum from either control or transgenic mice was similar. When control J774 macrophage cells were used, a comparison of efflux to serum or lipoprotein-deficient serum (LPDS) failed to demonstrate any differences between control and transgenic mice. In contrast, when the J774 cells were pretreated with cAMP, there was a stimulation of efflux to whole serum or LPDS from HuA-IVTg mice. cAMP treatment had no effect on efflux to serum or LPDS from control mice. Pretreatment of the cells with cAMP did not enhance the efflux response to high density lipoprotein isolated from HuA-IVTg mouse serum. Our results suggest that apoA-IV, unassociated with high density lipoprotein particles, is responsible for enhanced cholesterol efflux. This study illustrates the role of lipid-free apolipoproteins in mediating cellular cholesterol efflux with use of a biological fluid and is potentially of physiological relevance, especially in apolipoprotein-rich extravascular fluids.

Animals↗
PubMed1999

Ambulatory blood pressure profiles in essential hypertensives after treatment with a new once daily nifedipine formulation.

The antihypertensive efficacy of a new controlled-release preparation of nifedipine developed for once daily administration was investigated in comparison with a standard therapy with sustained-release nifedipine given twice daily in a randomised, open crossover trial. Twenty-two patients with mild to moderate essential hypertension were enrolled. Ambulatory blood pressure monitoring (ABPM) was performed after a wash-out period and after a 3 weeks treatment with 40 mg controlled-release nifedipine once daily and 20 mg sustained-release nifedipine twice daily, respectively. ABPM data were evaluated by conventional linear analysis and by rhythm analysis. Both once daily and twice daily administration of nifedipine significantly reduced systolic blood pressure during the daytime and during the night when compared with baseline. The 24-h diastolic blood pressure was significantly decreased by both treatments, but only the once daily regimen significantly lowered both diastolic daytime and night-time means. Comparing systolic and diastolic blood pressures after both treatments, however, no significant differences were obtained. Both nifedipine treatments did neither greatly modify the circadian blood pressure pattern nor reflexly increase heart rate. In conclusion, once daily application of the controlled-release formulation of nifedipine resulted in a consistent and significant blood pressure reduction. Once daily and twice daily medications of nifedipine were about equally effective in lowering the elevated blood pressures.

Adult↗
PubMed1999

Intravascular ultrasound and stent implantation: intraobserver and interobserver variability.

BACKGROUND: Intravascular ultrasound (IVUS) imaging can be used to optimize implantation of intracoronary stents; the variability of the measurements, however, remains unclear. Our aim in this study was to determine the intraobserver and interobserver variability of IVUS measurements after stent implantation. METHODS: Ninety-four patients underwent implantation of 100 Palmaz-Schatz stents in 98 lesions (79 de novo and 19 restenotic). IVUS measurements (3.5F, 30 MHz) of proximal and distal reference sections and of the smallest stent lumen were performed by 2 investigators. RESULTS: Intraobserver and interobserver correlations, respectively, were r = 0.96 and 0.93 for the proximal reference, r = 0.94 and 0.92 for the distal reference, and r = 0.97 and 0.97 for minimal stent lumen. Stent expansion (minimal lumen in the stent/mean reference area) showed a variability of r = 0.80 and 0.70. Taking a cutoff point of 90% for adequacy of stent expansion, observers agreed in only 77% whether the stent was adequately or inadequately expanded. CONCLUSIONS: IVUS enables reproducible lumen measurements in stents and reference sections. The degree of stent expansion, however, underlies a high measurement variability that can lead to different therapeutic strategies.

Coronary Disease↗
PubMed1999

Comparison of the LDL-receptor binding of VLDL and LDL from apoE4 and apoE3 homozygotes.

Compared with apolipoprotein E3 (apoE3), apoE2 is less effective in mediating the binding of lipoproteins to the low-density lipoprotein (LDL) receptor. The influence of the E4 isoform, which is associated with adverse effects on plasma lipids and coronary heart disease, is less clear. We compared the ability of very low density lipoprotein (VLDL) and LDL from paired E4/4 and E3/3 subjects to compete against 125I-labeled LDL for binding with the LDL receptor on cultured fibroblasts and Hep G2 cells. The concentrations of VLDL or LDL required to inhibit binding of 125I-LDL by 50% (IC50, microgram apoB/ml) were determined, and results were assessed in terms of an IC50 ratio, E4/4 IC50 relative to E3/3 IC50, to reduce the influence of interassay variability. In Hep G2 cells, E4/4 VLDL was more effective than E3/3 VLDL in competing for the LDL receptor, the IC50 ratio being lower than unity (0.73 +/- 0.31, P < 0.05, two-tailed t-test). IC50 values themselves were marginally lower in E4/4 than E3/3 subjects (3.7 +/- 1.3 vs. 6.1 +/- 3.7, P < 0.08). However, there was no difference between E4/4 and E3/3 VLDL in competing for the LDL receptor on fibroblasts or between E4/4 and E3/3 LDL in competing for the LDL receptor on either cell type. These results suggest that inheritance of apoE4 is associated with an increased affinity of VLDL particles for LDL receptors on hepatocytes and may partly explain the influence of the E4 isoform on lipid metabolism.

Adult↗
PubMed1999

Incomplete expansion of Palmaz-Schatz stents despite high-pressure implantation technique: impact on target lesion revascularization.

Improved expansion of stents using high-pressure implantation technique with subsequent antiplatelet therapy has improved patient outcome regarding the incidence of subacute stent thrombosis, bleeding complications and restenosis. Whether high-pressure implantation per se guarantees adequate stent expansion remains unclear. The aim of the study was to determine (1) stent expansion after high-pressure implantation technique and (2) whether stent expansion influences rate of target lesion revascularization within 6 months of follow-up. One hundred Palmaz-Schatz stents were implanted in 98 lesions (91 native vessels, 7 graft vessels) of 94 patients using high-pressure implantation technique (balloon pressure 12-20 atm). Stent expansion was investigated using intravascular ultrasound imaging (IVUS). Clinical follow-up of the patients was performed for 6 months. After implantation, stent/mean reference ratio was 0.81 +/- 0.16. Noncompliant balloons used for implantation were chosen by angiographic criteria. Mean balloon/reference ratio was 1.08 +/- 0.22; therefore balloons were not undersized. Additional balloon dilataion using higher pressures and/or larger balloons based on IVUS criteria and subsequent IVUS measurements was performed in 52 patients (55%); in these patients, stent expansion improved from 79 +/- 16 to 91 +/- 15% (mean +/- SD) of average reference areas (p < 0.002). Within the 6 months' clinical follow-up, target lesion revascularization was performed in 19 patients (20%). The only prognostic factors for the development of in-stent restenosis requiring target lesion revascularization were the vessel size (p < 0.05) and the extent of plaque distal to the stents (p < 0.05). Implantation of Palmaz-Schatz stents using high-pressure technique does not guarantee adequate stent expansion. Additional dilatation with higher pressures and/or larger balloons improves stent expansion. The size of the stented vessel and the extent of plaque at the distal stent end (residual outflow stenosis) but not the degree of stent expansion were predictors for target lesion revascularization within 6 months' follow-up.

Adult↗
PubMed1999

Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: a paraffin immunohistochemical study.

In this study, we assessed the frequency of cyclin D1 protein expression in normal and neoplastic parathyroid tissue (10 parathyroid carcinomas, 28 adenomas, 18 hyperplasias, and 32 normal parathyroid glands) with use of a monoclonal anticyclin D1 antibody and a heat-induced epitope retrieval method. Overexpression of cyclin D1 was identified in 10 (91%) of 11 biopsy specimens from 10 patients with parathyroid carcinomas and in 11 (39%) of 28 parathyroid adenomas. In addition, 11 (61%) of 18 cases of parathyroid hyperplasia also expressed cyclin D1 protein, an observation not reported previously. These results confirm the high frequency of cyclin D1 expression in parathyroid carcinomas and adenomas. In addition, the results of this study indicate that overexpression of cyclin D1 protein is not limited to neoplastic proliferations of parathyroid tissue but is also seen in non-neoplastic proliferations of parathyroid gland. Cyclin D1 protein expression was rarely (<6%) present in normal parathyroid tissue.

Adenoma↗
PubMed1998

How to standardize vasomotor tone in serial studies based on quantitation of coronary dimensions?

In patients with coronary artery disease including those after coronary bypass graft operation and heart transplantation intervention studies based on serial quantitative coronary angiography, in part combined with intravascular ultrasound, are of increasing relevance. Since vasomotor tone of epicardial coronary arteries is influenced by a variety of factors, angiographic follow-up studies require standardization of coronary tone by induction of maximal dilation. We reviewed the effects of the most potent coronary vasodilatory drug groups, calcium antagonists and nitrocompounds, on coronary diameters. Intravenous or intracoronary injections of verapamil, diltiazem, nifedipine, nicardipine, and nisoldipine can cause profound coronary dilation which has been shown to be maximal with verapamil and nisoldipine. Shortcomings of calcium antagonists include short or unknown duration of action after bolus administration, severe drop in blood pressure, and lack of commercial availability of solutions for injection of many substances. Isosorbide dinitrate induces profound coronary dilation; however, after sublingual administration marked blood pressure decrease can occur, and the duration of action and ideal dose of intracoronary isosorbide dinitrate has not been investigated yet. Injections of molsidomine and its active metabolite, SIN-1, cause longlasting, reproducible, maximal coronary dilation, although only after a waiting period of at least 10 minutes; unfortunately, SIN-1 is only commercially available in France. Nitroglycerin induces reproducible maximal coronary dilation and is easy to administer sublingually or as intracoronary bolus injection with rapid onset of action and no major side effects. The short duration of action may require repeated administrations. To date, repeated intracoronary bolus injections of 0.1 mg nitroglycerin every 10 minutes seem to be the optimal known regimen for standardization of coronary vasomotor tone in serial angiographic studies. Further investigations in this field with old and new vasodilatory drugs are recommendable.

Calcium Channel Blockers↗
PubMed1998

Impact of the Location of Recurrent Stenosis on Revascularization after Coronary Palmaz-Schatz Stent Implantation.

In 69 patients the incidence of target lesion revascularization during 3-year follow-up after single Palmaz-Schatz stent implantation was compared with the in-stent location of recurrent stenoses at 6-month follow-up angiography. A stenosis was defined as a lesion with > 15% diameter stenosis. After stent implantation, 17 mid-type, 10 proximal and 5 distal-type residual stenoses were found. At follow-up, 56 mid-type, 11 proximal and 6 distal-type stenoses were measured. Only proximal-type residual stenoses revealed an increase in diameter stenosis (40 +/- 15% vs 27 +/- 6%; p < 0.05). Five out of 11 patients (45%) with proximal-type recurrent stenoses underwent revascularization during follow-up versus 8 out of 56 (14%) with mid-type and none of the 6 patients with distal-type stenoses (p = not significant). This clear trend Ñ toward more progression and target lesion revascularization procedures in proximal-type recurrent stenoses mainly developing from residual stenoses left after stent implantation Ñ should be verified in larger patient collectives.

Journal Article↗