Images in cardiology. Glycoprotein IIb/IIIa induced coronary thrombolysis.
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Biomedical subjects
Publications and source records attributed to B Henkel.
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This paper presents a new protecting group, the (2-nitrofluoren-9-yl)methoxycarbonyl group. Investigations on the properties of this new modification of the Fmoc-system, such as the solvent-dependent photochemical cleavage, and enhanced lability towards bases, are described, as well as UV-kinetic measurements of the cleavage reaction. In addition, the incorporation of the (2-nitrofluoren-9-yl)methoxycarbonyl group into two peptides, and a sequence-dependent photochemical cleavage reaction are reported.
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Highly substituted proline analogues were synthesized on Wang-resin bearing bisprotected histidine as starting material. The proline analogues (1,5-diazabicyclo[3.3.0]octane-2-carboxylic acid) were generated by 1,3-dipolar cycloaddition of azomethine ylides with maleimides, thus creating a library of maximum stereochemical diversity. Every compound set with the same empirical formula can theoretically consist of four diastereomers and can be tested in biological assays as mixture. Additionally different methods for the acylation of the proline nitrogen were evaluated.
Aggregation phenomena of growing peptides on the resin have seldom been investigated. We report here how conformations are determined by FT-IR spectroscopy. Therefore the sequence 80-99 of HIV 1-protease was synthesized. After every coupling a resin sample was taken out of the reaction column and a FT-IR spectrum recorded. The results were compared with the UV monitoring obtained from another synthesis of the same peptide.
Analysis of 14.162 kb of DNA derived from plasmid pO157 of enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain EDL933, extending in the 5' direction of the recently described EHEC-hly operon, revealed 13 open reading frames (ORF) which showed great similarities to genes of members of the type II pathway secretion systems of Gram-negative bacteria. We named the ORFs etpC to etpO for EHEC type II secretion pathway. In addition, an IS911-like insertion element was found to separate the etp genes from the EHEC-hlyC gene. Hybridization experiments with a specific etp probe and various categories of enteric E. coli pathotypes revealed that the etp gene cluster occurred in all 30 EHEC strains of serogroup O157 (100%) tested and is distributed sporadically among other EHEC serogroups (60%). In addition, the etp genes were rarely detected in STEC isolated from bovine feces (10%). Moreover, it was found not to occur in enteropathogenic E. coli, enteroaggregative E. coli, enterotoxigenic E. coli and enteroinvasive E. coli. The results obtained with the etp probe were confirmed by a PCR approach to specifically detect an internal fragment of the etpD gene.
A case is presented of an atypical arteriovenous coronary artery fistula which occurred in a young man who was admitted to hospital with constant stress-dependent dyspnea and a feeling of thoracic constriction. A continuous systolic-diastolic murmur above the 5th intercostal space to the left of the sternum was present. By means of transoesophageal echocardiography and heart catheterization a rather atypical bilateral coronary fistula was found. A bilateral coronary fistula had been formed from RCA and RCX which drained via a common intramural cavity into the right ventricle. The fistula was operatively closed. Bilateral coronary artery fistula are rare, being found with a frequency of 0.002-0.013% in heart catheterization. In 36 reported instances of bilateral fistulae it has been noted that drainage into the pulmonary artery is more common than is the case with single coronary artery fistulae. The therapeutic considerations correspond with those for single fistulae.
Porphyromonas gingivalis has been shown to exhibit genetic diversity possibly resulting in variation of virulence. In the present study a potential virulence factor was targeted for the detection of P. gingivalis. A 548 bp fragment of the collagenase gene (prtC) from Porphyromonas gingivalis ATCC 33277 was amplified by polymerase chain reaction (PCR) using oligonucleotides derived from the middle portion of prtC. From 16 of 21 clinical P. gingivalis strains, a PCR product of similar size to the prtC could be obtained. These 16 P. gingivalis strains were confirmed as positive for prtC using DNA hybridization with a digoxigenin-labeled prtC PCR product as a probe. In 12 of the 16 prtC positive strains, the restriction analysis of the PCR products revealed fragment patterns identical to the known sequence. In the other 4 prtC positive strains, 4 distinct patterns were found. Of these strains, nucleotide sequence analysis of a 400 bp PCR product stretch revealed 79.1%, 83.0%, 84.8 and 89.5% homology with the known nucleotide sequence for this specific region. Sequence analysis of the PCR products from the ATCC 33277 strain demonstrated 93.7% homology. The limit of detection for the PCR was about 100 organisms. None of the other 48 tested strains of 16 bacterial species derived from oral and extraoral infections yielded a PCR product. The PCR was also used for the detection of prtC sequences in dental plaque. Our data indicate that not all P. gingivalis strains have prtC. Nucleotide heterogeneity exists among P. gingivalis with prtC.(ABSTRACT TRUNCATED AT 250 WORDS)
Chicken vigilin was identified as a member of an evolutionary-conserved protein family with a unique repetitive domain structure. 14 tandemly repeated domains are found in chicken vigilin, all of which consist of a conserved sequence motif (subdomain A) and a potential alpha-helical region (subdomain B) [1]. We have established the physical structure of the chicken vigilin gene by restriction-fragment analysis and DNA sequencing of overlapping clones isolated from a phage lambda genomic DNA library. The chicken vigilin gene is a single-copy gene with a total of 27 exons which are distributed over a region of some 22 kbp. Exon 1 codes for a portion of the 5' untranslated region, exon 2 contains the translation start point and forms, along with exons 3 and 4, the N-terminal non-domain region. Exons 5-25 encode the vigilin domains 1-14 and the remaining exons 26 and 27 contain the non-domain C-terminal as well as the untranslated regions. The domain structure of the protein is reflected in the positioning of introns which demarcate individual domains. While domains 1-3 and 8-10 are each encoded by a single exon (5-7, 16-18); all other domains are contained in a set of two exons which are separated by introns interspersed at variable positions of the DNA segment coding for the conserved sequence motif. In conclusion, the data presented suggest that the chicken vigilin gene evolved by amplification of a primordial exon unit coding for the fundamental bipartite vigilin domain.
The complete cDNA (4375 bp), coding for a new protein called vigilin, was isolated from chicken chondrocytes. The cDNA shows an open reading frame of 1270 amino acids which are organized in 14 tandemly repeated homologous domains. Each domain consists of two subdomains, one with a conserved sequence motif of 35 amino acids (subdomain A) and another one with a presumptive alpha-helical structure of 21-33 amino acids (subdomain B). 149 amino acids at the N-terminus and 71 amino acids at the C-terminus of vigilin do not show the characteristic domain structure. No sequence characteristic of a signal peptide has been found, which argues for an intracellular localisation of vigilin. Vigilin is highly expressed in freshly isolated chicken chondrocytes but little in chondrocytes after prolonged time in culture. Vigilin mRNA exists in two size species, 4.4 kb and 6.5 kb in length due to the usage of different polyadenylation sites. Comparison of the vigilin sequence with data bases showed a remarkable similarity to protein HX from Saccharomyces cerevisiae [Delahodde, A., Becam, A. M., Perea, J. & Jacq, C. (1986) Nucleic Acids Res. 14, 9213-9214]. The yeast protein consists of eight homologous domains with 11 conserved amino acid residues within a set of 35 amino acids. The N-terminal and C-terminal regions of vigilin and protein HX do not reveal any sequence similarity. These results, together with the demonstration of the characteristic vigilin sequence motif in a human cDNA clone, suggest that the repeats represent evolutionary conserved autonomous domains within a family of proteins found in yeast, chicken and man.
Our results establish that myocardial regions supplied by a significantly stenosed coronary vessel can be distinguished with high statistical significance from healthy regions on account of changes in the myocardium/background ratio, i.e. a reduction of regional uptake of 15-(p-iodo-phenyl) pentadecanoic acid (pPPA). The statistical significance applies to patients with coronary artery disease (CAD), to all examined CAD areas without areas of infarction as well as to infarcted regions. Our results also confirm the suitability of labelled fatty acids, such as pPPA, for the visualization of damaged myocardial regions. The results further indicate that pPPA practically is of comparable value to 201Tl with regard to their respective qualities as 'static' imaging agents for the heart muscle. This study, with the help of a simultaneous analysis of regional myocardial perfusion rates (rMBF) and of a parameter for the metabolism of fatty acids, practised here for the first time, could demonstrate interindividual differences between patients and groups of patients with a correlation between perfusion and the utilization of pPPA in patients with CAD. The reciprocal of the rMBF, the mean transit time (MTT), was significantly prolonged after stress in patients with CAD (P less than 0.05), suggesting impaired 'microcirculation' in the patient group. The determination of elimination half-lives (T1/2) contributes little if any information towards delineation of cardiac disease entities. The wide overlap of T1/2 values between various clinical syndromes and entities with extreme standard deviations remained an annoying problem in our studies. Nevertheless, certain trends in T1/2 behaviour could be recorded, but they did not yield any statistical significances, because of the high degree of individual variability. A considerable variability of T1/2 values among healthy controls was recorded as well as intra-individually in different regions of the heart muscle. The wide range of 'normal' values rendered statistical evaluation almost, if not entirely, impossible. It appears that the high degree of variability results amongst others, from technical shortcomings in the external recording instruments, i.e. gamma cameras, as well as from the presence of interfering alternate substrates such as glucose and lactate. Nevertheless, the wide range of measured results in healthy control subjects suggests the presence of a considerable regional intra-individual heterogeneity of cardiac substrate metabolism. One must therefore accept, at least in our opinion, that T1/2 values are not sufficiently reliable as an indicator of myocardial metabolism and are of little value with respect to clinical diagnostic considerations and to prognosis as well. Possible explanations for this finding are offered and discussed in this paper.
The main glycophospholipid of Thermoplasma acidophilum, grown at 39 degrees C, is composed of a di-isopranol-2,3-glycerotetraether. It has been characterized in hydrated systems by calorimetry. Unlike its equivalent grown at 59 degrees C, it shows complex phase properties, which include at least three different phases, (1) a liquid-analogue state (C), which is stable above 20 degrees C, (2) a metastable solid-analogue state (A) formed by supercooling of the liquid-analogue state (C) and (3) a stable solid-analogue state (B), which is slowly formed and may include a close chain packing of lipids and a network of hydrogen bonds between the headgroups. A high fraction of acyclic isopranol chains seems to be a prerequisite for the formation of state (B). A phase diagram, displaying the observed states and the transitions between them is proposed.
The effects of mechanical ventilation with PEEP were investigated in five patients with normal cardiopulmonary function (group A) and in 11 patients with severe left ventricular failure (group B). Cross-sectional area of the right and left atrium (RA/LA), left ventricle (LV), and right ventricle (RV) was determined at EDA/ESA using transesophageal echocardiography. Hemodynamic parameters and transesophageal pressure were measured simultaneously at PEEP levels 0, 4, 8, 12, and 16 cm H2O. End-diastolic area of the right atrium decreased significantly in both groups. The RA pressure increased, while transmural pressure remained unaltered. The CI decreased in both groups. The decrease in cardiac output by PEEP ventilation was related to the decrease in RV filling volume by external compression. In patients with congestive heart failure, PEEP ventilation with 8 to 10 cm H2O did not worsen LV function.
127 patients, admitted within six hours of onset of symptoms of acute transmural myocardial infarction, received at first 250 000 U streptokinase intravenously over 20 min, followed by an intracoronary infusion of 250 000 U after coronary angiographic demonstration of the infarct vessel. Those in whom the infarct vessel was closed were randomized into two groups. An attempt at recanalization was made either by thrombolysis alone, through a specially developed 3F catheter (group I, 64 patients), or by thrombolysis and dilatation with 4F Grüntzig balloon catheter (group II, 63 patients). There was no significant difference between the two groups with regard to sex, age, infarct site, creatine-kinase level and interval between onset of symptoms and treatment. Re-perfusion rate for group I was 92% (59 patients), for group II 89% (56 patients). Re-occlusion during the hospital stay occurred in 10 of 59 patients in group I, in 9 of 55 in group II. Re-occlusion occurred in only 8% (3 patients) after successful dilatation, but in 35% (6 patients) after failed dilatation. In the subsequent six months further occlusions were observed in seven group I and two group II patients. Combined drug-mechanical recanalization thus increased the re-perfusion rate, shortened the infarction time and made possible full revascularization by subsequent dilatation which led to a reduction in the re-occlusion rate.
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Echocardiographic studies were performed in 105 patients with acute and recurrent pulmonary emboli. Pulmonary embolism was confirmed by pulmonary angiography (n = 48), autopsy (n = 6), and lung perfusion scintigraphy (n = 51). Seventy of 93 patients (75%) displayed a dilated right ventricle, 38 of 91 patients (42%) had reduced left ventricular cavity dimension, 41 of 82 patients (50%) had a decreased EF slope of the mitral valve, and 78 of 101 patients (77%) showed dilatation of the right pulmonary artery. The motion of the interventricular septum was abnormal in 41 of 93 patients (44%). Right-sided thrombi were seen in 13 patients within the right pulmonary artery (n = 11) and in the right ventricle (n = 3); in one patient they were found in the superior vena cava, in the innominate vein, and the right atrium. Two patients suffered from right-sided endocarditis. Thus echocardiographic changes were frequently found in patients with proved pulmonary emboli. The echocardiographic findings of right-sided cardiac and pulmonary artery abnormalities indicate hemodynamically active pulmonary emboli.
In 45 survivors of myocardial infarction, cardiac catheterization was performed one and six months after the acute event. After completion of the angiographic investigation, ventricular vulnerability was assessed, using programmed right ventricular stimulation (rates 120 and 140 min-1, single and double premature impulses). In 27/45 patients the results of programmed electrical stimulation were comparable at one and six months. The overall incidence of repetitive ventricular response did not change. There was no correlation between the change of repetitive ventricular response and the change of effective right ventricular refractory period and the change of angiographic parameters (Gensini score, left ventricular ejection fraction and volume indices). It is concluded that between the first and the sixth month after infarction there is no relevant alteration in the propensity to repetitive ventricular response.
In 51 normal subjects (26 men, 25 women, age range 15-38 years), normal values for longitudinal axis and diameters of left and right ventricle and left and right atrium were determined by 2-D echocardiography. Both left parasternal longitudinal and cross-sectional cuts were used. Tolerance values to determine normal range were recorded, in addition to mean values and standard deviations. Diastolic and systolic diameters (DD/DS) in the left parasternal longitudinal and cross-sectional cuts gave similar results to those in the 4-chamber view from the apex: DD 2.7 +/- 0.4 (2.3-3.1) cm/m2, DS 1.8 +/- 0.4 (1.4-2.2) cm/m2, and DD 2.7 +/- 0.4 (2.3-3.1) cm/m2, DS 1.7 +/- 0.3 (1.4-2.0) cm/m2, respectively. Sizes of the right ventricle (1.8 +/- 0.4/1.4-2.2 cm/m2) and right atrium (2.4 +/- 0.5/1.9-2.9 cm/m2) could only be obtained in the 4-chamber view. Values for the left atrium (2.3 +/- 0.7/1.6-3.0 cm/m2) were obtained also in the left parasternal cross-section. Correcting for body surface, differences between males and females were reduced to the extent that there was no significant difference between them. These normal values make it possible to standardize the measurement of intracardiac dimensions by 2-D echocardiography and classify individual values.