Search PubMed⌕ Search

Biomedical subjects

M Horn

Publications and source records attributed to M Horn.

At least 19 recordsLinked to original sources
PubMed2001

Development of a technology for automation and miniaturization of protein crystallization.

The usage of standard 96 well microplates for the screening of crystallization conditions of recombinant proteins offers several advantages when compared to commonly used crystallization plate formats. The adoption of robotic technology for plate and glass slide preparation within a "hanging drop" vapour diffusion crystallization experiment enables to work with an increased throughput at reduced costs. In addition to commercial pipetting devices with a 96-channel aspirator/dispenser, solenoid ink-jet technology was applied to form 250 nl droplets with a diameter of approximately 1 mm. This allows miniaturization of crystallization screening set-ups with an estimated ten-fold cost reduction when compared to commonly used 24 well plates.

Concanavalin A↗
PubMed2001

Detection of myocardial viability based on measurement of sodium content: A (23)Na-NMR study.

MRI of total sodium (Na) content may allow assessment of myocardial viability, but information on Na content in normal myocardium, necrotic/scar tissue, and stunned or hibernating myocardium is lacking. Thus, the aims of the study were to: 1) quantify the temporal changes in myocardial Na content post-myocardial infarction (MI) in a rat model (Protocol 1); 2) compare Na in normally perfused, hibernating, and stunned canine myocardium (Protocol 2); and 3) determine whether, in buffer-perfused rat hearts, infarct scar can be differentiated from intact myocardium by (23)Na-MRI (Protocol 3). In Protocol 1, rats were subjected to LAD ligation. Infarct/scar tissue was excised at control and 1, 3, 7, 28, 56, and 128 days post-MI (N = 6-8 each), Na content was determined by (23)Na-NMR spectroscopy (MRS) and ion chromatography. Na content was persistently increased at all time points post-MI averaging 306*-160*% of control values (*P < 0.0083 vs. control). In Protocol 2, (23)Na-MRS of control (baseline), stunned and hibernating samples revealed no difference in Na. In Protocol 3, (23)Na-MRI revealed a mean increase in signal intensity, to 142 +/- 6% of control values, in scar tissue. A threshold of 2 standard deviations of the image intensity allowed determination of infarct size, correlating with histologically determined infarct size (r = 0.91, P < 0.0001).

Animals↗
PubMed2001

Simulated limnological effects of the Shasta Lake temperature control device.

We estimated the effects of a temperature control device (TCD) on a suite of thermodynamic and limnological attributes for a large storage reservoir, Shasta Lake, in northern California. Shasta Dam was constructed in 1945 with a fixed-elevation penstock. The TCD was installed in 1997 to improve downstream temperatures for endangered salmonids by releasing epilimnetic waters in the winter/spring and hypolimnetic waters in the summer/fall. We calibrated a two-dimensional hydrodynamic reservoir water quality model, CE-QUAL-W2, and applied a structured design-of-experiment simulation procedure to predict the principal limnological effects of the TCD under a variety of environmental scenarios. Calibration goodness-of-fit ranged from good to poor depending on the constituent simulated, with an R2 of 0.9 for water temperature but 0.3 for phytoplankton. Although the chemical and thermal characteristics of the discharge changed markedly, the reservoir's characteristics remained relatively unchanged. Simulations showed the TCD causing an earlier onset and shorter duration of summer stratification, but no dramatic affect on Shasta's nutrient composition. Peak inreservoir phytoplankton production may begin earlier and be stronger in the fall with the TCD, while outfall phytoplankton concentrations may be much greater in the spring. Many model predictions differed from our a priori expectations that had been shaped by an intensive, but limited-duration, data collection effort. Hydrologic and meteorological variables, most notably reservoir carryover storage at the beginning of the calendar year, influenced model predictions much more strongly than the TCD. Model results indicate that greater control over reservoir limnology and release quality may be gained by carefully managing reservoir volume through the year than with the TCD alone.

Climate↗
PubMed2001

Alterations in myocardial creatinine kinase (CK) and lactate dehydrogenase (LDH) isoenzyme-distribution in a model of left ventricular dysfunction.

The purpose of the current study was to evaluate myocardial creatinine kinase (CK) and lactate dehydrogenase (LDH) systems in a model of epinephrine-induced cardiomyopathy in rabbits. Eight rabbits received four repetitive epinephrine infusions (300 mg/kg/60 min, i.v.) in 12-day intervals and eight untreated rabbits served as controls (CTRL). Echocardiography demonstrated a significant deterioration of LV function as well as increased LV-diameter and -mass index in catecholamine-induced cardiomyopathy. Histological examination revealed that repetitive catecholamine infusion resulted in LV fibrous areas with collagenous content and an increase in myocyte width (16.9+/-0.8 microm vs. CTRL 12.9+/-0.9; P<0.05). LV dysfunction was associated with a decreased total LV lactate dehydrogenase activity (LDH; 0.43+/-0.03 IU/mg protein vs. CTRL 0.52+/-0.04; P<0.05) whereas total creatinine kinase activity was unchanged (CK; 7.30+/-0.63 IU/mg protein vs. CTRL 9.20+/-0.49, n.s.). Furthermore, myocardial LDH isoenzymes were shifted with a decrease in LDH(1) and an increase in LDH2 and LDH3 (LDH(1): 84.90+/-2.60% vs. CTRL 94.50+/-0.40; LDH2: 7.30+/-1.20% vs. 1.50+/-0.13; LDH3: 5.40+/-0.90% vs. 3.20+/-0.25; all P<0.05). Foetal B-CK isoenzymes were significantly increased (CK-MB 5.30+/-0.66 vs. 2.20+/-0.35%; P<0.05). The current study demonstrates changes in cardiac energy metabolism including an impaired LDH activity with a shift towards anaerobic isoenzymes as well as a more efficient CK system in a model of catecholamine-induced LV dysfunction.

Animals↗
PubMed2000

Na(+)/H(+) exchange inhibition with HOE642 improves postischemic recovery due to attenuation of Ca(2+) overload and prolonged acidosis on reperfusion.

BACKGROUND: Na(+)/H(+) exchange inhibition with HOE642 (cariporide) improves postischemic recovery of cardiac function, but the mechanisms of action remain speculative. Because Na(+)/H(+) exchange is activated on reperfusion, it was hypothesized that its inhibition delays realkalinization and decreases intracellular Na(+) and, via Na(+)/Ca(2+) exchange, Ca(2+) overload. Attenuated Ca(2+) overload and prolonged acidosis are known to be cardioprotective. METHODS AND RESULTS: Left ventricular developed and end-diastolic pressures were measured in isolated buffer-perfused rat hearts subjected to 30 minutes of no-flow ischemia and 30 minutes of reperfusion (37 degrees C) with or without 1 micromol/L HOE642 added to the perfusate 15 minutes before ischemia. Intracellular Ca(2+) concentration ([Ca(2+)](i)) and pH(i) were measured with aequorin (n=10 per group) and (31)P NMR spectroscopy (n=6 per group), respectively. HOE642 did not affect preischemic mechanical function, [Ca(2+)](i), or pH(i). Mechanical recovery after 30 minutes of reperfusion was substantially improved with HOE642: left ventricular developed pressure (in percent of preischemic values) was 92+/-3 versus 49+/-7 and left ventricular end-diastolic pressure was 16+/-3 versus 46+/-5 mm Hg (P<0.05 for HOE642-treated versus untreated hearts). End-ischemic [Ca(2+)](i) was significantly lower in HOE642-treated than in untreated hearts (1.04+/-0.06 versus 1.84+/-0. 02 micromol/L, P<0.05). Maximal intracellular Ca(2+) overload during the first 60 seconds of reperfusion was attenuated with HOE642 compared with untreated hearts: 2.0+/-0.3 versus 3.2+/-0.3 micromol/L (P<0.05). pH(i) was not different at end ischemia ( approximately 5.9+/-0.05). Realkalinization was similar in the first 90 seconds of reperfusion and significantly delayed in the next 3 minutes (eg, 6.8+/-0.07 in HOE642-treated hearts compared with 7. 2+/-0.07 in untreated hearts; P<0.05). CONCLUSIONS: HOE642 improves postischemic recovery by reducing Ca(2+) overload during ischemia and early reperfusion and by prolonging postischemic acidosis.

Acidosis↗
PubMed2000

Impact of beverage acceptability on fluid intake during exercise.

These two studies investigated the impact of beverage acceptability on voluntary fluid intake during exercise and the subsequent impact of exercise on the perception and liking of beverages. In Experiment 1, 49 triathletes and runners first tasted an array of 10 commercially available flavors of a 6% carbohydrate-electrolyte drink (CE) and water (W) to determine the most-acceptable flavor (M) and least-acceptable flavor (L) for each subject. Subjects were subsequently given M, L, or W ad libitum during 180 min of exercise. Drink acceptability was again measured after 90 and 180 min of exercise. Drink intake was measured at 15-min intervals. Intake of M was significantly greater than L and W throughout the first 75 min and significantly greater than W throughout the entire exercise period. In Experiment 2, subjects were given M+W, or L+W, in a two-bottle procedure. Voluntary intake of M and L exceeded W by 318% and 233%, respectively. An unexpected finding was a strong interaction between drink acceptability and exercise state. The acceptability of L increased substantially from sedentary to exercise conditions. These data demonstrated that the flavored, sweetened beverages used in this study, substantially increased voluntary fluid intake over W.

Adult↗
PubMed2000

Three-dimensional (13)C-spectroscopic imaging in the isolated infarcted rat heart.

Acquisition weighted (13)C-spectroscopic imaging with three spatial dimensions is demonstrated in the isolated, perfused rat heart. Experiments were performed at 11.75 T with a home-built double resonant (13)C-(1)H probehead. Three-dimensional chemical shift imaging was used to obtain (1)H-decoupled (13)C-spectra in 96-microl voxels in about 58 min. Acquisition weighting significantly reduced signal contamination and improved image quality, with no penalty in sensitivity. As a first application, infarcted hearts were studied during perfusion with [2-(13)C]-sodium acetate. The extent of the incorporation of the (13)C-label into glutamate allows us to distinguish intact and infarcted myocardium. Chemical shift images show a homogeneous glutamate distribution in intact tissue, but a negligible amount in the infarction scar.

Animals↗
PubMed2000

[Cardiac energy metabolism in heart valve diseases with 31P MR spectroscopy].

PURPOSE: Heart valve disease combined with left ventricular hypertrophy leads to derangements in cardiac energy metabolism, which can be detected non-invasively by 31P-MR-spectroscopy. The purpose of the present study was to examine whether the derangements in cardiac metabolism are reversible after surgical valve replacement. PATIENTS AND METHODS: 10 healthy volunteers and 10 patients with aortic stenosis (pressure gradients > 60 mmHg) were included. For assessment of energy metabolism, 31P-MR spectra were obtained with a double oblique 3D-CSI technique (voxel size 25 cm3). In 5 of 10 patients, follow-up examination was performed 3 months after surgical valve replacement (SVR). Left ventricular (LV) function was analyzed by cine MRI. RESULTS: Before SVR the myocardial phosphocreatine to adenosinetriphosphate (PCr-ATP) ratio was significantly (p = 0.0002) reduced to 0.80 +/- 0.25 in patients compared to 1.65 +/- 0.21 in volunteers. 3 months after SVR, LV mass had significantly (p = 0.04) decreased from 238 +/- 33 g to 206 +/- 47 g. At the same time a significant (p = 0.04) increase of the PCr-ATP ratio from 0.80 +/- 0.25 to 1.28 +/- 0.22 was observed. A slight, but not significant, reduction of the phosphodiester ATP ratio was observed before SVR, with a trend towards normalization after SVR. CONCLUSIONS: After SVR, the deranged energy metabolism shows a trend towards normalization. Further follow-up is necessary to determine whether complete normalization of the energetic derangement can be observed over longer periods of time following SVR.

Adult↗
PubMed2000

[Carotid endarterectomy and carotid stenting. A pilot study of a prospective, randomized and controlled comparison].

INTRODUCTION: A prospective, randomized and controlled trial is conducted to compare carotid endarterectomy and carotid stenting in high grade symptomatic carotid artery stenoses. METHODS: According to the study design symptomatic patients with a angiographically high-grade (> or = 70%) internal carotid artery stenosis are included. Pre- and postinterventional diagnostics during the hospitalization period includes neurological assessment, duplex sonography of the cervical and cerebral arteries and magnetic resonance imaging of the brain. Follow-up examinations are scheduled after 1, 6 and 12 months and consist of a neurological assessment and duplex sonography. After 12 months selective angiography and magnetic resonance imaging of the brain will be performed additionally. During a period of 9 months up to now 23/137 patients treated for a carotid artery stenosis were included in the study, 11 patients underwent surgery and 12 patients carotid stenting. RESULTS: Carotid stenting and endarterectomy was primarily successful without residual stenosis > 30% in each patient without the occurrence of stroke or death. In 18 follow-up examinations (neurological assessment including duplex sonography) of 13 patients (13 follow-up examinations after 30 days, 5 after 6 months) no relevant restenosis and no stroke occurred. CONCLUSION: As of yet, carotid stenting was a safe procedure. Due to the small number of patients a definitive conclusion can not be drawn.

Angiography, Digital Subtraction↗
PubMed2000

Altered energy metabolism after myocardial infarction assessed by 31P-MR-spectroscopy in humans.

The value of 31P-magnetic resonance spectroscopy (MRS) as a possible tool to distinguish viable from non-viable tissue after myocardial infarction was analysed in humans. Fifteen patients 3 weeks after anterior myocardial infarction were studied with breath-hold cine MRI and 3D-CSI MRS (1.5 T system). 31P-spectra were obtained from infarcted as well as non-infarcted myocardium (voxel size 25 cm3 each). Gold standard for viability was recovery of regional function, as determined by a control MRI 6 months after revascularization. Ten age-matched healthy volunteers served as control group. No significant difference was found between the phosphocreatine to adenosinetriphosphate (PCr/ ATP) ratio of volunteers (SD 1.72+/-0.31) and non-infarcted septal myocardium of patients. Cine MRI demonstrated recovery of regional function in 10 patients, i. e. 10 patients showed viable and 5 non-viable myocardium. In viable myocardium, the PCr/ATP ratio was 1.47+/-0.38 (non-significant vs volunteers; p>0.05). In the 5 patients with akinetic myocardium, PCr peaks could not be detected. Therefore, calculation of PCr/ATP ratios was not possible. However, a significant reduction of the ATP signal-to-noise ratio (SNR) was observed (2.92+/-0.73 vs 6.68+/-0.80; patients vs volunteers; p<0.05). The SNR of ATP of akinetic regions may predict recovery of function after revascularization in patients with myocardial infarction.

Adenosine Triphosphate↗
PubMed2000

An apparent outbreak of cutaneous papillomatosis in merino sheep in patagonia, Argentina.

A retrospective study was performed on skin samples from an outbreak of cutaneous papillomatosis in Merino sheep that occurred in 1995. The samples were processed for routine histology, electron microscopy and immunocytochemistry for papilloma viruses. Particles of approximately 55 nm diameter were found in some nuclei of the stratum granulosum cells, while immunocytochemistry gave positive staining of cell nuclei in this layer. This study confirms that papillomas associated with papillomaviruses occur in sheep in Patagonia.

Animals↗
PubMed2000

Arginine-based structures are specific inhibitors of cathepsin C. Application of peptide combinatorial libraries.

Novel synthetic peptide inhibitors of lysosomal cysteine proteinase cathepsin C have been designed through the use of soluble peptide combinatorial libraries. The uncovered structural inhibitory module consists of the N-terminal cluster of L-arginine residues. Its modification with D-amino acids or arginine derivatives did not increase the inhibition strength. Inhibitory potency of oligoarginines improves with the elongation of peptide chain reaching a maximum for octa-L-arginine. The oligoarginines specifically interact with the cathepsin C active site as shown by competitive-type inhibition kinetics (Ki approximately 10-5 M) and intrinsic fluorescence measurements. The inhibitory interaction of oligoarginines is established through the specific spatial contact of a net of guanidino groups in the arginine side-chains, as indicated by comparison with inhibitory action of low molecular mass guanidine derivatives (Ki approximately 10-3 M). Nonarginine polyionic compounds cannot mimic the inhibitory effect of oligoarginines. The arginine-based peptide inhibitors were selective towards cathepsin C among other cysteine proteinases tested.

Animals↗
PubMed2000

Topical treatment with liposomes containing T4 endonuclease V protects human skin in vivo from ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha.

Exposing human skin to ultraviolet radiation causes DNA damage, sunburn, immune alterations, and eventually, skin cancer. We wished to determine whether liposomes containing a DNA repair enzyme could prevent any of the acute effects of irradiation when applied after ultraviolet exposure. Fifteen human patients with a prior history of skin cancer were exposed to two minimal erythema doses of ultraviolet radiation on their buttock skin. Liposomes containing T4 endonuclease V or heat-inactivated enzyme were applied immediately and at 2, 4, and 5 h after ultraviolet irradiation. Transmission electron microscopy after anti-T4 endonuclease V-staining and immunogold labeling on biopsies taken at 6 h after ultraviolet exposure revealed that the enzyme was present within cells in the skin. Immunohistochemical DNA damage studies suggested a trend toward improved DNA repair at the active T4 endonuclease V liposome-treated test sites. Although the active T4 endonuclease V liposomes did not significantly affect the ultraviolet-induced erythema response and microscopic sunburn cell formation, they nearly completely prevented ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha RNA message and of interleukin-10 protein. These studies demonstrate that liposomes can be used for topical intracellular delivery of small proteins to human skin and suggest that liposomes containing DNA repair enzymes may provide a new avenue for photoprotection against some forms of ultraviolet-induced skin damage.

Administration, Topical↗
PubMed2000

Sample size determination for testing whether an identified treatment is best.

Laska and Meisner (1989, Biometrics 45, 1139-1151) dealt with the problem of testing whether an identified treatment belonging to a set of k + 1 treatments is better than each of the other k treatments. They calculated sample size tables for k = 2 when using multiple t-tests or Wilcoxon-Mann-Whitney tests, both under normality assumptions. In this paper, we provide sample size formulas as well as tables for sample size determination for k > or = 2 when t-tests under normality or Wilcoxon-Mann-Whitney tests under general distribution assumptions are used.

Biometry↗
PubMed2000

Gastric emptying of cold beverages in humans: effect of transportable carbohydrates.

Eight healthy subjects, aged 39.0 ¿ 2.4 years, consumed four 6% carbohydrate-electrolyte solutions containing either one (glucose or fructose) or two transportable carbohydrates in single (glucose + fructose) or bound (sucrose) forms. Solution osmolalities ranged from 250 to 434 mOsm/kg H2O. The test solutions were ingested at rest in the amount of 6 ml/kg of body weight at a temperature of 12 ¿C. Gastric emptying rate was measured by repeated aspirations via a nasogastric tube using the modified George double-sampling technique. The intragastric temperature was determined by a temperature probe attached to the nasogastric tube. There were no significant differences in gastric emptying rates and gastric volumes among the solutions. Intragastric temperature dropped from 36.5 ¿C to 23.3 ¿ 3 ¿C immediately after beverage ingestion but recovered to above 30 ¿C within 5 min. These data suggest that the gastric emptying rate of the specified beverages is not affected by the number and type of carbohydrates or by solution osmolalities within the tested range. Within 5 min after ingestion, cold beverages are warmed to above 30 C in the stomach. This infers that the effect of cold solution temperature on gastric emptying rate is likely to be small and transitory.

Adult↗