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Biomedical subjects

R Hoffmann

Publications and source records attributed to R Hoffmann.

At least 109 records · Page 6Linked to original sources
PubMed2000

Assessment of myocardial reperfusion by intravenous myocardial contrast echocardiography and coronary flow reserve after primary percutaneous transluminal coronary angioplasty [correction of angiography] in patients with acute myocardial infarction.

BACKGROUND: This study investigated whether the extent of perfusion defect determined by intravenous myocardial contrast echocardiography (MCE) in patients with acute myocardial infarction (AMI) treated by primary percutaneous transluminal coronary angioplasty (PTCA) relates to coronary flow reserve (CRF) for assessment of myocardial reperfusion and is predictive for left ventricular recovery. METHODS AND RESULTS: Twenty-five patients with first AMI underwent intravenous MCE with NC100100 with intermittent harmonic imaging before PTCA and after 24 hours. MCE before PTCA defined the risk region and MCE at 24 hours the "no-reflow" region. The no-reflow region divided by the risk region determined the ratio to the risk region. CFR was assessed immediately after PTCA and 24 hours later. Left ventricular wall motion score indexes were calculated before PTCA and after 4 weeks. CFR at 24 hours defined a recovery (CFR >/=1.6; n=17) and a nonrecovery group (CFR <1.6; n=8). Baseline CFR did not differ between groups. MCE ratio to the risk region was smaller in the recovery group compared with the nonrecovery group (34+/-49% vs 81+/-46%, P=0.009). A ratio to the risk region of </=50% defined an MCE reperfusion group. It was associated with improvement of CFR from 1.67+/-0.47 at baseline to 2. 15+/-0.53 at 24 hours (P<0.001) and of regional wall motion score index from 2.6+/-0.5 to 1.9+/-0.5 at 4 weeks (P<0.001). CONCLUSIONS: Intravenous MCE can be used to define perfusion defects after AMI. Assessment of microcirculation by MCE corresponds to evaluation by CFR. Serial intravenous MCE has the potential to identify patients likely to have improved left ventricular function after AMI.

Aged↗
PubMed2000

Glycosaminoglycan-binding properties and secondary structure of the C-terminus of netrin-1.

Netrins are soluble neurite-outgrowth-promoting proteins related to the laminin B2 chain. Since these proteins and their receptor DCC (the "deleted in colorectal carcinoma" gene product) bind heparin, glycosaminoglycans may modulate their biological actions in a similar fashion as described for several other ligand-receptor systems. Here we show that a polypeptide encompassing the C-terminal cluster of basic amino acids of netrin-1 (i) adopts an alpha-helical conformation in water-trifluoroethanol mixtures according to circular dichroism experiments and (ii) binds electrostatically to heparin with high affinity under physiological ionic conditions (K(D) = 15 nM for the binding to immobilized heparin according to surface plasmon resonance, K(D) = 50 nM in solution as determined with isothermal titration calorimetry). These data indicate that the cluster of basic amino acids at the C-terminus of netrin-1 forms an alpha-helical structural element which can contribute to the glycosaminoglycan-binding activity of this neurotrophic guidance molecule.

Amino Acid Sequence↗
PubMed2000

Association of hepatitis C virus-specific CD8+ T cells with viral clearance in acute hepatitis C.

CD8+ T lymphocytes play a major role in antiviral immune defense. Their significance for acute hepatitis C is unclear. Our aim was to correlate the CD8+ T cell response with the outcome of infection. Eighteen patients with acute hepatitis C and 19 normal donors were studied. Hepatitis C virus (HCV)-specific CD8+ T cells were identified in the enzyme-linked immunospot assay by their interferon-gamma (IFN-gamma) production after specific stimulation. The highest numbers of IFN-gamma-producing HCV-specific CD8+ T cells were found in patients with acute hepatitis C and a self-limited course of disease during the first 6 months after onset of disease, but these numbers dropped thereafter to undetectable levels. The differences in responsiveness between patients with self-limited disease versus patients with a chronic course were statistically significant (P<.001). Our data show that the number of IFN-gamma-producing HCV-specific CD8+ T cells during the first 6 months after onset of disease is associated with eradication of the HCV infection.

Acute Disease↗
PubMed2000

Low temperature scanning force microscopy of the Si(111)-(7x7) surface

A low temperature scanning force microscope (SFM) operating in a dynamic mode in ultrahigh vacuum was used to study the Si(111)- (7x7) surface at 7.2 K. Not only the twelve adatoms but also the six rest atoms of the unit cell are clearly resolved for the first time with SFM. In addition, the first measurements of the short range chemical bonding forces above specific atomic sites are presented. The data are in good agreement with first principles computations and indicate that the nearest atoms in the tip and sample relax significantly when the tip is within a few A of the surface.

Journal Article↗
PubMed2000

Purification and characterization of an aminopeptidase from the chloroplast stroma of barley leaves by chromatographic and electrophoretic methods.

Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or peptide substrates. Although some aminopeptidase activities have been found in plant chloroplasts, the identity of these proteins remains unclear. In this work, we report the purification to apparent homogeneity of a soluble aminopeptidase from isolated barley chloroplasts which preferentially degraded alanyl-p-nitroanilide (Ala-pNA). After organelle isolation in a density gradient and precipitation of soluble proteins with ammonium sulfate, the proteins were purified in three consecutive steps including hydrophobic interaction, gel permeation and ion-exchange chromatographies. The purified enzyme appeared as a single band with a Mr of approximately 84000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The Mr of the native enzyme was estimated to be approximately 93000 by gel permeation chromatography, suggesting that the protein is a monomer. Mass spectrometry analysis of tryptic digests indicates that the primary structure of the protein has not been reported previously. The enzyme was characterized as a metalloprotease as it could be totally inhibited by 1,10-phenanthroline. Strong inhibition could also be observed using the specific aminopeptidase inhibitors amastatin and bestatin. Besides Ala-pNA, the purified protein could also cleave with decreasing activity glycyl-pNA, leucyl-pNA, lysyl-pNA, methionyl-pNA and arginyl-pNA. The possible physiological role of this enzyme in the chloroplast stroma is discussed.

Aminopeptidases↗
PubMed2000

In situ stimulation of a T helper cell hybridoma with a cellulose-bound peptide antigen.

Many enzyme-linked immunosorbent assays take advantage of immobilized antigens for the identification of antibody binding sites. Generally, the analysis of cellulose membrane-bound B-cell epitopes is currently considered of high utility. We adapted this methodology for the stimulation of a T helper cell hybridoma with known specificity. Forty overlapping peptides corresponding to the entire rabies virus nucleoprotein were synthesized in duplicates on a single sheet of 90x130 mm size amino-modified paper. The efficacy of the peptide assembly was monitored by color staining of the unreacted amino groups. After completion of the synthesis, the side-chain protecting groups were removed, and the membrane was thoroughly cleaned of all organic and inorganic contaminants. The membrane was cut into pieces, and a standard lymphokine release assay was performed directly from the paper-bound antigens. From all the 40 peptide spots only peptide 31D stimulated the proliferation of the 9C5.D8-H T-cell hybridoma, known to react to this peptide. By using this protocol, as little as 0.4 microgram (approximately 200 pmole) of peptide could be detected. According to mass spectrometry the T-cell stimulation proceeded as a true solid-phase assay. The peptide neither leached from the membrane nor was cleaved by the medium-splenocyte mixture. Additionally, tryptic digestion of the cellulose membrane released the expected peptide fragments.

Amino Acid Sequence↗
PubMed2000

Studies on the dephosphorylation of phosphotyrosine-containing peptides during post-source decay in matrix-assisted laser desorption/ionization.

Phosphorylation of tyrosine residues in proteins is a common regulatory mechanism, although it accounts for less than 1% of the total O-phosphate content in proteins. Whereas aromatic phosphorylation sites can be identified by a number of different analytical techniques, sequence analysis of phosphotyrosine-containing proteins at the low picomole or even femtomole level is still a challenging task. This paper describes the post-source decay in matrix-assisted laser desorption/ionization mass spectrometry of phosphotyrosine-containing model peptides by comparing their fragmentation behavior with sequence-homologous unphosphorylated peptides. Whereas the parent ions showed significant losses of HPO3, all phosphorylated fragment ions of the b- and y-series displayed only minor dephosphorylated signals, which often were not detectable. Surprisingly, one of the studied phosphotyrosine-containing sequences displayed, in addition to the [M + H - 80]+ ion, a more abundant [M + H - 98]+ ion, which could be explained by elimination of phosphoric acid. This dephosphorylation pattern was very similar to the patterns obtained for phosphoserine- and phosphothreonine-containing peptides. Because the dephosphorylation pattern of the parent ion is often used to identify modified amino acids in peptides, we investigated possible dephosphorylation mechanisms in detail. Therefore, we substituted single trifunctional amino acid residues and incorporated deuterated phosphotyrosine residues. After excluding direct elimination of phosphoric acid from tyrosine, we could show that the obtained loss of H3PO4 depends on aspartic acid and arginine residues. Most likely the HPO3 group is transferred to aspartic acid followed by cleavage of phosphoric acid forming a succinimide. On the other hand, arginine appears to induce the H3PO4 loss by protonation of phosphotyrosine leaving a phenyl cation.

Phosphopeptides↗
PubMed2000

Lesion-to-lesion relationship of the restenosis process after placement of coronary stents.

The interrelation between multiple stented lesions within one patient in the restenosis process is only partially understood. From 492 patients with follow-up angiograms after coronary stent placement, 115 patients underwent multilesion procedures involving 233 lesions. In randomly chosen 39 patients with 79 lesions, additional intravascular ultrasound (IVUS) studies were performed to measure intimal hyperplasia cross-sectional area (CSA) and thickness. A general linear model with intraclass correlation was used to calculate the coefficient of correlation rho (rho = 1.0 indicates perfect correlation; rho = 0.0 indicates no correlation) of late loss, late loss index, intimal hyperplasia CSA, and intimal hyperplasia thickness. Multivariate analysis showed restenosis in the companion lesion (odds ratio 4.68, 95% confidence interval 1. 68-12.92, P = 0.003) and small minimal lumen diameter preintervention (odds ratio 0.28, 95% confidence interval 0.11-0.73, P = 0.009) to be predictors of restenosis. There was a weak correlation between multiple lesions within the same patient for late lumen loss rho = 0.28 (95% confidence interval 0.10-0.46, P < 0. 001) and late loss index. IVUS analysis demonstrated correlation of intimal hyperplasia CSA rho = 0.40 (95% confidence interval 0.06-0. 74, P = 0.009) and of intimal hyperplasia thickness. In conclusion, late loss and intimal hyperplasia demonstrate a correlation between multiple stented lesions within one patient. In addition to known lesion related factors, restenosis in a companion lesion is a predictor for restenosis. Cathet. Cardiovasc. Intervent. 51:266-272, 2000.

Aged↗
PubMed2000

[Operative treatment of complex acetabular fractures through the modified extensile iliofemoral approach].

Fourty-nine patients with 50 complex acetabular fractures were treated with open reduction and internal fixation from August 1993 to February 1996 in a prospectively documented study. The fractures were fixed with small fragment implants through a modified extensile iliofemoral approach (Maryland approach). Thirty-seven patients were polytraumatized with an ISS of 20 pts. on average. In 10 patients the ISS was > 25 pts. Good or anatomic initial fracture reduction with a fragment stepoff K 2 mm could be achieved in 48 fracturers (96 %). Thirty-six patients with 37 fractures could be evaluated after 25 months on average. In 28 fractures (76 %) the functional outcome was good or excellent according to the d'Aubigne and Harris scores. Radiological results were excellent in 21 fractures (57 %) and satisfactory in 12 fractures (Heeg score). In 7 cases (14 %) a postoperative subcutaneous seroma had to be treated surgically. No wound infections, however, were observed. Further complications were secondary a loss of reduction in 4 cases (11 %), relevant heterotopic ossifications (Brooker III/IV) in 5 cases (14 %), and aseptic femoral head necrosis in 2 cases (5 %). In two cases a total hip replacement (THR) for posttraumatic arthritis had to be performed. Two more cases are scheduled for THR due to symptomatic femoral head necrosis. A good joint reconstruction can be achieved through the modified extensile iliofemoral approach (Maryland) in complex fractures of the acetabulum. However, the approach related morbidity seems to be worrisome. In complex fractures with comminution in the roof of the acetabulum the prognosis remains uncertain even in cases where initial anatomic joint reconstruction can be achieved.

Acetabulum↗
PubMed2000

Screw fixation of acetabular fractures.

Between 1992 and 1995, 50 patients with 51 acetabular fractures underwent internal fixation using 3.5 mm cortical screws. There were 21 simple and 30 associated fracture types, as described by Letournel. Most of the patients had sustained multiple injuries with an average injury severity score (ISS) of 20 points. The modified extended iliofemoral approach was used in 32 cases, the Kocher Langenbeck approach in 9 cases, the ilioinguinal approach in 7 cases, the extended iliofemoral in 2 cases and the Kocher-Langenbeck approach combined with an ilioinguinal approach in a second stage procedure in 1. Anatomical reduction could be achieved with persistent displacement of no more than 1 mm in 40 fractures. Implant failure with loss of reduction occurred in 3 patients who underwent a revision procedure. At 2 year follow-up, 38 out of 44 of the patients had excellent or good clinical and radiological results. In acetabular fractures with sufficiently large fragments, screw fixation with 3.5 mm cortical screws proved satisfactory. In very comminuted fractures or where there is poor patient compliance an additional buttress plate should be used.

Acetabulum↗
PubMed2000

[Improved endocardial border delineation during dobutamine stress echocardiography using the left heart contrast medium BY 963].

UNLABELLED: The interpretation of induced wall motion abnormalities during dobutamine stress echocardiography is affected in the case of impaired image quality. In 48 consecutive patients (mean age 62 +/- 9 years, 32 males, 16 females) with suspected coronary disease undergoing coronary angiography, the transpulmonary contrast agent BY 963 was given i.v. as bolus during dobutamine stress echocardiography (10-40 micrograms kg min, plus max. 1 mg atropine) to analyze improvements in endocardial border delineation. For each of the 16 segments of the left ventricle, the endocardial border delineation was evaluated. Using BY 963 the average number of non-evaluable segments decreased by 58% from 5.2% to 2.2% at rest (p = 0.008) and by 56% from 5.9% to 2.6% at maximal stress (p = 0.003) as compared to the non-contrast study for all patients. In patients with impaired image quality, defined as at least 1 non-evaluable segment at rest without contrast enhancement (N = 14), the number of non-evaluable segments decreased from 19.2% to 8.2% (p = 0.004) at rest and from 19.2% to 9.6% (p = 0.006) at maximal stress. The greatest decrease of non-evaluable segments was seen in the lateral and anterior segments of the apical views (maximum of 80%). The improved endocardial border delineation resulted in an improved agreement between two observers in the interpretation of the dobutamine stress echocardiograms as positive or negative (kappa = 0.38 without contrast, kappa = 0.58 with contrast). Contrast application resulted in a slight improvement of diagnostic accuracy of dobutamine stress echocardiography in the detection of angiographically proven significant coronary artery disease. CONCLUSION: In patients with impaired endocardial border delineation the use of the echo contrast agent BY 963 reduces the number of non-evaluable segments. Improvement of endocardial delineation is greatest for lateral and anterior segments in the apical views.

Aged↗
PubMed2000

Vannella sp. harboring Microsporidia-like organisms isolated from the contact lens and inflamed eye of a female keratitis patient.

Viable Hartmannella sp. and two strains of Vannella sp.--but no Acanthamoebae--multiplied on NN-agar inoculated with pieces of the contact lens from a female keratitis patient. Within the cytoplasm of one Vannella isolate, intracellular parasites could be observed whose earliest stages were developing within the nucleus, resembling those Microsporidia-like parasites seen within Vannella isolated recently from a warm tapwater system. This assumption was also confirmed by electron microscopy. In swabs taken directly from the cornea, Pseudomonas aeruginosa were identified, but they did not yield any growth of amebas in culture. However, cocultivation of parasite-free Vannella strains with the above-mentioned swab matter resulted in infected amebas harboring the same intracellular parasites seen before. This infection could be established only if the corresponding spores were present as infective agents in the swab matter. The successful treatment of the patient with antibiotics supports the assumption that P. aeruginosa was the main cause of the corneal ulceration. The extent to which the Microsporidia-like organisms may have been involved in the development of keratitis remains a matter of discussion.

Adult↗
PubMed2000

Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI.

BACKGROUND & AIMS: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection. METHODS: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. RESULTS: Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). CONCLUSIONS: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.

Adult↗
PubMed2000

Studies on structure-activity relationships of retinoic acid receptor ligands by means of molecular modeling.

Vitamin A and its biologically active derivatives, retinal and retinoic acid, play an important role in vision, are required for reproduction, act as morphogenic agents during embryonic development, and regulate the growth and differentiation of a wide variety of cell types throughout the life of an organism. The biological action of retinoic acid and synthetic analogs, referred to as retinoids, is mediated by RAR alpha, RAR beta, or RAR gamma and/or by RXR alpha, RXR beta, or RXR gamma, all being nuclear receptors. Since retinoids exert profound effects on cell proliferation, differentiation, and apoptosis, these compounds seem to be promising agents for the treatment of cancer. Consequently, a large number of retinoids have been synthesized and examined to determine if they exert their biological activity according to retinoic acid receptor interaction. These screening methods are often expensive, time-consuming, and labor-intensive procedures. Since one can construct the pharmacophores of congeneric groups of drug molecules, molecular modeling techniques offer a new way to determine the binding abilities of different agents. We examined the structural properties of retinoids, which allow them to specifically bind to the different receptor subtypes. The thus-generated 3D pharmacophore models were used to predict the binding affinities of several retinoids to the retinoic receptor subtypes. Finally, the 3D models served as criteria for searching the Derwent World Drug Index for compounds that possess the features necessary for favorable ligand receptor interaction. The search resulted in a "hit list" containing 323 compounds, some of which are worth further investigation to determine if they act via retinoic acid receptor binding or not.

Computer Simulation↗
PubMed2000

Mechanical properties and imaging characteristics of remanufactured intravascular ultrasound catheters.

Intravascular ultrasound (IVUS) as a routine device in interventional cardiology is handicapped by its high price. 19 factory-made, 'remanufactured' IVUS catheters which consist of sterilized, used phased-array IVUS transducers inserted into a new catheter shaft were compared with 23 new IVUS catheters. 3 mechanical and 4 imaging characteristics were assessed on a 5 point scale (1 = unacceptable, 5 = excellent). Mechanical as well as imaging properties of 'remanufactured' IVUS catheter were comparable to new catheters with excellent ratings for each of the evaluated characteristics in 38 to 94% of 'remanufactured' catheters and 50 to 96% of new catheters. The initial failure rate for 'remanufactured' IVUS catheters was 31.6% vs. 4.3% for new catheters (P < 0.05). Overall failure rate was 47.3% for "remanufactured" catheters vs. 8.7% for new catheters (P < 0.05). The failure was due to an electronic connecting problem occurring during mechanical stress to the IVUS catheter. In conclusion, 'remanufactured' IVUS catheters offer mechanical and imaging characteristics which are comparable to new catheters. Improvements in the 'remanufacturing' process to resolve the high rate of electronic connecting problems may make this a promising approach to substantially lower the price of IVUS catheters.

Catheterization↗
PubMed2000

Treatment with an anti-CD44v10-specific antibody inhibits the onset of alopecia areata in C3H/HeJ mice.

A murine CD44v10-neutralizing antibody has been reported to impair delayed-type hypersensitivity reactions. Because alopecia areata is characterized by a delayed-type hypersensitivity-like T cell mediated immune response, we addressed the question whether an anti-CD44v10-antibody influences the onset of alopecia areata. Therefore, we used the C3H/HeJ mouse model with the induction of alopecia areata in unaffected mice by the grafting of lesional alopecia areata mouse skin. Six grafted mice were injected (intraperitoneally) with anti-CD44v10, six grafted mice with anti-CD44standard, and six with phosphate-buffered saline only. After 11 wk phosphate-buffered saline injected animals on average had developed alopecia areata on 36.8% of their body. The onset of hair loss was slightly delayed and its extent reduced to 17.2% of their body in anti-CD44standard-treated mice. By contrast, five of six anti-CD44v10-treated mice did not show any hair loss and one mouse developed alopecia areata on only 1% of the body. Immunohistochemical examination revealed a marked reduction of perifollicular CD8+ lymphocytes and, to a lesser degree, CD4+ cells as well as a decreased expression of major histocompatibility complex class I on hair follicle epithelium in anti-CD44v10-treated mice as compared with phosphate-buffered saline or anti-CD44 standard-treated mice. Our data show that anti-CD44v10 is able to inhibit the onset of alopecia areata in C3H/HeJ mice. This might be accomplished by an anti-CD44v10-triggered impairment of immune cell homing (e.g., CD8+ T cells), resulting in a decrease of their number in target tissues.

Alopecia Areata↗
PubMed2000

Rapid quantification of left ventricular function and mass using transoesophageal three-dimensional echocardiography: validation of a method that uses long-axis cutplanes.

AIMS: Despite its proven superiority compared to conventional echocardiographic techniques, three-dimensional (3D) echocardiography has not gained widespread acceptance in clinical medicine for the quantification of left ventricular volumes, function and mass. This is mainly due to the large, time-consuming process of data analysis. We sought to validate a new method that enables the accurate quantification of the left ventricle in a clinically acceptable short period of time. METHODS AND RESULTS: Left ventricular volumes, ejection fraction and mass were determined in 44 patients using 3D echocardiography. The 3D echocardiographic data sets were analysed: (i) using the conventional 'summation of slices' algorithm (slice thickness 5 and 10mm), which is based on the analysis of the 3D reconstructed left ventricle in short-axis cross-sections; and (ii) using the new method which is based on the analysis of the 3D reconstructed left ventricle in long-axis images. In each patient measurements were repeated using 3, 6, 7, 8, 9, 12 and 15 long-axis images. For all volumetric measurements there was a continuous reduction of measurement variability using increasing numbers of long-axis images. The use of more than nine long-axis images for volumes, and eight long-axis images for ejection fraction and mass, did not result in a further reduction of variability. The analysis time for volumes and masses averaged less than 5 min for the long-axis method using nine component images, compared to 20-43 min for the short-axis method. CONCLUSION: 3D echocardiography combined with a novel method based on the analysis of long-axis cross-section allows accurate quantification of left ventricular volumes, function and mass in a clinically acceptable short period of time. In the future, the combination of a real-time 3D echocardiographic acquisition technique with this analysis method should have important implications for the introduction of 3D echocardiography in clinical practice.

Echocardiography, Three-Dimensional↗