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Biomedical subjects

M Schartl

Publications and source records attributed to M Schartl.

At least 109 records · Page 6Linked to original sources
PubMed1994

Intravascular ultrasound imaging in patients with acute myocardial infarction: comparison with chronic stable angina pectoris.

BACKGROUND: Myocardial infarction is the result of acute thrombotic occlusion of a coronary artery, most likely secondary to rupture of an atherosclerotic plaque. Intracoronary ultrasonic (ICUS) examinations were performed in patients with acute myocardial infarction (AMI) in order to describe intraluminal ultrasonic findings at the site of acute coronary occlusion. METHODS: Coronary angiography and ICUS studies were performed consecutively within 6 h of the onset of chest pain in 30 patients with AMI prior to percutaneous transluminal coronary angioplasty (PTCA). The control group consisted of 30 patients with chronic stable angina pectoris (SAP). Following angiographic documentation of a proximal stenosis or occlusion, a 3.5 or 4.8 F mechanical ultrasound catheter (20 MHz) was advanced successfully through the lesion in 25 of 30 (83%) patients with AMI and in 15 of 30 (50%) patients with SAP (P < 0.01). RESULTS: Intracoronary ultrasound permitted differentiation between pulsatile, low-echogenic intraluminal material suggesting thrombus and mural highly echogenic atherosclerotic plaque in 22 of 25 (88%) patients with AMI. A negative imprint of the ICUS catheter was documented within the low-echogenic material in 17 of 25 (68%) patients with AMI. Low-echogenic intraluminal material was found in 18 of 25 (72%) segments proximal and in 12 of 25 (48%) segments distal to the highly echogenic plaque, indicating prestenotic and post-stenotic thrombus in AMI. The plaque appeared eccentric in 22 of 25 (88%) patients with AMI. In comparison, stenotic lesions in chronic SAP patients were less frequently eccentric (5/15, 33%, P < 0.01) and contained a higher proportion of pure highly echogenic material (12/15, 80%). Cross-sectional area stenosis due to highly echogenic plaque averaged 52 +/- 13% in AMI and 82 +/- 3% in SAP (P < 0.01). Calcification of plaque was evident in 21 of 25 patients with AMI (SAP 12/15, 80%, NS). The surface of the plaque was rough in 13 of 25 (52%) AMI patients (SAP 4/15, 27%, P < 0.05). Fissures were detected in only seven (28%) patients and dissection was observed in two (8%) cases. The low incidence might be a result of the limited resolution of the ICUS system. CONCLUSION: This study demonstrates that ICUS with 4.8 or 3.5 F catheters is feasible and safe in selected patients with AMI, and adds little to the overall duration of the angioplasty procedure. The identification and demarcation of atherosclerotic plaque provided by ICUS could prove valuable in guiding PTCA, in deciding on appropriate therapy, and in acute and long-term follow-up of AMI patients.

Adult↗
PubMed1994

Remodeling of myocardium and arteries by chronic angiotensin converting enzyme inhibition in hypertensive patients.

AIM: To investigate changes in left ventricular hypertrophy and diastolic function in hypertensive patients treated with an angiotensin converting enzyme (ACE) inhibitor. METHODS: Structural and functional changes in the heart and iliac artery were studied by echocardiography and intraluminal ultrasound in 15 hypertensive patients following 6 months of treatment with the ACE inhibitor quinapril at 10-40 mg/day. RESULTS: Systolic/diastolic blood pressure was reduced from 156/100 mmHg to 128/82 mmHg within 2 months and remained stable during the next 4 months of the study. The left ventricular mass index was significantly reduced from 174 +/- 86 to 161 +/- 75 g/m2 (-7.4%, P < 0.05). The reduction in left ventricular hypertrophy was associated with a trend towards an improvement in diastolic function, but left ventricular systolic function did not change. There was a 3.9% increase in iliac lumen area and a significant decrease of 10.7% (P < 0.05) in the ratio between the intimal-medial and lumen area, which represents a decrease in wall thickness. A key result was a statistically significant decrease in pulse-wave velocity, from 13.7 +/- 2.6 to 12.1 +/- 2.0 m/s, and in the modulus of elasticity, from 20.5 +/- 7.2 to 15.8 +/- 5.6 x 10(4) N/m2 (P < 0.05). CONCLUSION: The present study demonstrates that 6 months of treatment with an ACE inhibitor induced a significant regression in left ventricular hypertrophy and a reduction in wall thickness. In addition, the results indicate that chronic ACE inhibition can decrease the stiffness of large elastic arteries independently of a reduction in blood pressure.

Aged↗
PubMed1994

[Stress echocardiography--an evaluation of current status].

Exercise echocardiography, a versatile, noninvasive diagnostic test of left ventricular wall motion performed at rest and under induced stress, enables the cardiologist to detect and assess coronary artery disease. Stress-induced ischemia is thereby expressed as left ventricular regional wall motion abnormality. By using various physical (bicycle or treadmill exercise) and pharmacological (dipyridamole, dobutamine, adenosine) stress inducers, the test provides information about the localization and extent of coronary artery disease in addition to detecting stress-induced coronary insufficiency. As regards diagnostic accuracy in detecting coronary artery disease, stress echocardiography is superior to exercise electrocardiography and, according to the available data, it is comparable to perfusion scintigraphic testing. Studies have demonstrated the clinical value of stress echocardiography in detecting residual stenosis after angioplasty, for diagnosing bypass dysfunction after heart surgery, for preoperative risk assessment in noncardiac surgeries, and for obtaining prognostic information, e.g., after myocardial infarction. Preliminary studies have shown that pharmacological exercise echocardiography is able to identify viable myocardium in the early phases after acute myocardial infarction. Furthermore, it is able to predict the functional success of revascularization in chronic regional left ventricular dysfunction. In addition to the wide range of diagnostic possibilities in coronary artery disease, other notable applications include stress testing for assessment of global left ventricular pump function in patients with aortic regurgitation or cardiomyopathy.

Adenosine↗
PubMed1994

Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene.

Xmrk encodes a subclass I receptor tyrosine kinase (RTK) which has been cloned from the melanoma-inducing locus Tu of the poeciliid fish Xiphophorus. To demonstrate a high oncogenic potential in vivo we transferred the gene into early embryos of the closely related medakafish. Ectopic expression of the Xmrk oncogene under the control of a strong, constitutive promoter (CMVTk) led to the induction of embryonic tumors with high incidence, after short latency periods, and with a specific pattern of affected tissues. We demonstrate ligand-dependent transformation in vivo using a chimeric receptor consisting of the extracellular and transmembrane domains of the human EGF receptor (HER) and the cytoplasmatic domain of Xmrk. Expression of the chimeric receptor alone does not lead to kinase activation or induction of tumors. Coexpression of the chimera with its corresponding ligand, human transforming growth factor alpha (hTGF alpha), however, results in the activation of the chimeric RTK. In injected fish embryos the induction of the neoplastic growth is observed with similar incidence and tissue distribution as in embryos carrying the native Xmrk oncogene suggesting that the ligand as well as factors downstream of the RTK are required for tumor formation. In this study we show single-step induction of tumors by ectopic expression of RTKs in vivo substantiating the significance of autocrine stimulation in RTK induced tumors in vertebrates.

Animals↗
PubMed1993

Sequence of the growth hormone (GH) gene from the silver carp (Hypophthalmichthys molitrix) and evolution of GH genes in vertebrates.

The silver carp (Hypophthalmichthys molitrix) growth hormone (GH) gene was isolated and sequenced following amplification from genomic DNA by the polymerase chain reaction. The gene spans a region of approx. 2.5 kb nucleotides (nt) and consists of five exons. The sequence predicts a polypeptide of 210 amino acids (aa) including a putative signal peptide of 22 hydrophobic aa residues. The arrangement of exons and introns is identical to the GH genes of common carp, grass carp, and very similar to mammals and birds, but quite different from that for the GH genes of tilapia and salmonids. The silver carp GH gene shares a high homology at the nt and aa levels with those of grass carp (95.3% nt, 99.5% aa) and of common carp (81% nt, 95.7% aa).

Amino Acid Sequence↗
PubMed1993

Different expression patterns of oncogenes and proto-oncogenes in hereditary and carcinogen-induced tumors of Xiphophorus.

Hereditary melanoma in Xiphophorus hybrids carrying the melanoma-inducing Tu-Sd locus is caused by transcriptional activation of the Xmrk gene that resides at the Tu-Sd locus and encodes a novel member of receptor tyrosine kinases (RTK). In this study, a total of 27 hereditary melanomas from various hybrid genotypes harbouring 7 different Tu alleles were also found to over-express the corresponding Xmrk alleles. The level of over-expression correlated with the degree of malignancy of the melanoma. In addition, Xsrc expression was high in many malignant melanomas. Expression patterns and levels of the Xiphophorus EGF-receptor gene (Xerb B), the c-myc (Xmyc), and the PDGF (Xsis) gene(s) were not intriguing. Transcription of the ras gene(s) may be correlated to secondary events of melanoma progression. Expression patterns of Xfms, the Xiphophorus CSF-I receptor homologue, can be explained by different contents of infiltrating macrophages in the tumors. In carcinogen-induced tumors including one melanoma no significant expression of the Xmrk oncogene could be detected. Xsrc expression, however, was strikingly high. This indicates that activation of oncogenes other than Xmrk is instrumental in tumorigenesis of neoplasia of non-hereditary origin.

Animals↗
PubMed1993

Reproductive failure of dominant males in the poeciliid fish Limia perugiae determined by DNA fingerprinting.

Hierarchical structures among male individuals in a population are frequently reflected in differences in aggressive and reproductive behavior and access to the females. In general, social dominance requires large investments, which in turn then may have to be compensated for by high reproductive success. However, this hypothesis has so far only been sufficiently tested in small mating groups (one or two males with one or two females) due to the difficulties of determining paternity by conventional methods. DNA fingerprinting overcomes these problems by offering the possibility to determine genetic relationships and mating patterns within larger groups [Burke, T. (1989) Trends Ecol. Evol. 4, 139-144]. We show here that in the poeciliid fish Limia perugiae, in small mating groups the dominant male has a mating success of 100%, whereas in larger groups its contribution to the offspring unexpectedly drops to zero.

Animals↗
PubMed1993

Primitive sex chromosomes in poeciliid fishes harbor simple repetitive DNA sequences.

The demonstration of the chromosomal mode of sex determination via genetic experiments as well as the absence of heteromorphic sex chromosomes affirm poeciliid fishes as a unique group among vertebrates that are endowed with the most primitive form of sex chromosomes. In many different taxa the evolutionary process involved in the differentiation of advanced sex chromosomes is outlined through sex specifically organized repetitive sequences. In this investigation hybridization of synthetic probes specific to genomic simple repeat motifs uncovers a sex-specific hybridization pattern in certain viviparous fishes of the family Poeciliidae. The hybridization pattern together with specific staining of the constitutive heterochromatin by C-banding reveals heterogamety in males (Poecilia reticulata) as well as in females (P. sphenops). In P. velifera, however, C-banding alone fails to unravel the heterogametic status. The female specific W-chromosome can be detected by simple repetitive sequence probes. Therefore, the principal significance of heterochromatization as a means of generating differentiated sex chromosomes is evident.

Animals↗
PubMed1993

Tumor suppression in Xiphophorus by an accidentally acquired promoter.

Melanoma formation in the teleost Xiphophorus is caused by a dominant genetic locus, Tu. This locus includes the Xmrk oncogene, which encodes a receptor tyrosine kinase. Tumor induction is suppressed in wild-type fish by a tumor suppressor locus, R. Molecular genetic analyses revealed that the Tu locus emerged by nonhomologous recombination of the Xmrk proto-oncogene with a previously uncharacterized sequence, D. This event generated an additional copy of Xmrk with a new promoter. Suppression of the new Xmrk promoter by R in parental fish and its deregulation in hybrids explain the genetics of melanoma formation in Xiphophorus.

Amino Acid Sequence↗
PubMed1993

[Stress echocardiography: evaluation of left ventricular function after administration of the transpulmonary echo contrast medium SHU 508 A].

Stress echocardiography has recently gained increased importance as a method for assessment of left ventricular function. However, suboptimal image quality in some patients may limit use of this technique. In the present study, 10 patients with moderate image quality in the resting echocardiograms (apical 4-chamberview) were reinvestigated after administration of the intravenous transpulmonary saccharide-based left heart contrast agent SHU 508 A. Duration of contrast enhancement in the left ventricle determined by visual assessment was 135 s (SEE +/- 39) at rest and 112 s (+/- 24) during maximum exercise. On a scale ranging from O (no contrast) to 4 (excessively strong contrast) enhancement averaged 2.5 at rest and during exercise. The left ventricle was divided into three segments (septum, apex, lateral wall) and delineation of the endocardial border was assessed. Detection of the border improved significantly after contrast administration, especially at the lateral wall. Despite better visual assessment of the endocardial border, there was no improvement in automatic or semi-automatic contour recognition. No clinically significant side-effects were observed. Three patients reported a sensation of warmth at the injection site. In conclusion, intravenous administration of SHU 508 A improves visual detection of the left ventricular endocardial border in patients with suboptimal image quality and helps to achieve acceptable diagnostic accuracy with stress echocardiography in these patients.

Aged↗
PubMed1992

Structure of the rainbow trout metallothionein A gene.

To investigate the regulation of metallothionein-encoding genes in fish, we have isolated and sequenced the rainbow trout metallothionein-A-encoding gene (tMT-A) by polymerase chain reaction. This gene spans about 1.1 kb, consists of three exons and two introns, and has an A+T-rich 5'-region which contains a TATAAA signal, and two metal responsive elements (MREs). The transcription start point is centered around an A residue 81 nt upstream of the ATG codon.

Amino Acid Sequence↗
PubMed1992

The Xmrk receptor tyrosine kinase is activated in Xiphophorus malignant melanoma.

Xmrk encodes a putative transmembrane glycoprotein of the tyrosine kinase family and is a melanoma-inducing gene in Xiphophorus. We attempted to investigate the biological function of the putative Xmrk receptor by characterizing its signalling properties. Since a potential ligand for Xmrk has not yet been identified, it has been difficult to analyse the biochemical properties and biological function of this cell surface protein. In an approach towards such analyses, the Xmrk extracellular domain was replaced by the closely related ligand-binding domain sequences of the human epidermal growth factor receptor (HER) and the ligand-induced activity of the chimeric HER-Xmrk protein was examined. We show that the Xmrk protein is a functional receptor tyrosine kinase, is highly active in malignant melanoma and displays a constitutive autophosphorylation activity possibly due to an activating mutation in its extracellular or transmembrane domain. In the focus formation assay the HER-Xmrk chimera is a potent transforming protein equivalent to other tyrosine kinase oncoproteins.

Amino Acid Sequence↗
PubMed1992

Early stages of sex chromosome differentiation in fish as analysed by simple repetitive DNA sequences.

Animal sex chromosome evolution has started on different occasions with a homologous pair of autosomes leading to morphologically differentiated gonosomes. In contrast to other vertebrate classes, among fishes cytologically demonstrable sex chromosomes are rare. In reptiles, certain motifs of simple tandemly repeated DNA sequences like (gata)n/(gaca)m are associated with the constitutive heterochromatin of sex chromosomes. In this study a panel of simple repetitive sequence probes was hybridized to restriction enzyme digested genomic DNA of poeciliid fishes. Apparent male heterogamety previously established by genetic experiments in Poecilia reticulata (guppy) was correlated with male-specific hybridization using the (GACA)4 probe. The (GATA)4 oligonucleotide identifies certain male guppies by a Y chromosomal polymorphism in the outbred population. In contrast none of the genetically defined heterogametic situations in Xiphophorus could be verified consistently using the collection of simple repetitive sequence probes. Only individuals from particular populations produced sex-specific patterns of hybridization with (GATA)4. Additional poeciliid species (P. sphenops, P. velifera) harbour different sex-specifically organized simple repeat motifs. The observed sex-specific hybridization patterns were substantiated by banding analyses of the karyotypes and by in situ hybridization using the (GACA)4 probe.

Animals↗
PubMed1992

Brain-derived neurotrophic factor is more highly conserved in structure and function than nerve growth factor during vertebrate evolution.

Mammalian nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of a protein family with perfectly conserved domains arranged around the cysteine residues thought to stabilize an invariant three-dimensional scaffold in addition to distinct sequence motifs that convey different neuronal functions. To study their structural and functional conservation during evolution, we have compared NGF and BDNF from a lower vertebrate, the teleost fish Xiphophorus, with the mammalian homologues. Genomic clones encoding fish NGF and BDNF were isolated by cross-hybridization using probes from the cloned mammalian factors. Fish NGF and BDNF were expressed by means of recombinant vaccinia viruses, purified, and their neuronal survival specificities for different classes of neurons were found to mirror those of the mammalian factors. The half-maximal survival concentration for chick sensory neurons was 60 pg/ml for both fish and mammalian purified recombinant BDNF. However, the activity of recombinant fish NGF on both chick sensory and sympathetic neurons was 6 ng/ml, 75-fold lower than that of mouse NGF. The different functional conservation of NGF and BDNF is also reflected in their structures. The DNA-deduced amino acid sequences of processed mature fish NGF and BDNF showed, compared to mouse, 63% and 90% identity, respectively, indicating that NGF had reached an optimized structure later than BDNF. The retrograde extrapolation of these data indicates that NGF and BDNF evolved at strikingly different rates from a common ancestral gene about 600 million years ago. By RNA gel blot analysis NGF mRNA was detected during late embryonic development; BDNF was present in adult brain.

Amino Acid Sequence↗
PubMed1992

Multiple src-related kinase genes, srk1-4, in the fresh water sponge Spongilla lacustris.

In one of the simplest metazoan organisms, the sponge Spongilla lacustris, at least four different src-related kinase genes (srk1-4) are expressed, all of which show a high degree of similarity to the c-src genes of vertebrates. Whereas srk2 and srk3 are clearly unrelated at the nucleic acid level, srk1 and srk4 share identical sequences in the 5' parts of their cDNAs. The cloning of several primer extension clones and genomic polymerase chain reaction experiments confirmed the hypothesis of an alternative splicing of tandemly arranged carboxy-terminal parts of srk1 and srk4. The genomic sequence encoding both proteins was found to be interrupted at the splice point by an intron which is located in the same position as one of the introns in the chicken src gene, which is the only gene conserved in invertebrates and vertebrates. All four srk genes are expressed in adult sponges as mRNA transcripts of about 2.2 kb. Tyrosine kinase activity of a src-related kinase could be detected in adult sponges but not in their resting form (gemmulae), and may reflect the activity of the srk protein products. Spongilla lacustris is the simplest organism from which a protein tyrosine kinase gene has been isolated. The presence of at least four such genes in the evolutionary ancient and primitive phylum Porifera suggests that tyrosine kinase genes arose concomitantly with or shortly after the appearance of multicellular organisms and that their activity may be involved in aggregation and cell-cell recognition.

Amino Acid Sequence↗