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Biomedical subjects

M Schartl

Publications and source records attributed to M Schartl.

At least 145 records · Page 8Linked to original sources

Localization of cellular src mRNA during development and in the differentiated bipolar neurons of the adult neural retina in Xiphophorus.

The expression of the c-src gene in embryonic and adult tissue of the teleost fish Xiphophorus helleri was analyzed by in-situ hybridization. The highly conserved fish c-src gene was found to be expressed at high levels in midterm embryos, where c-src mRNA was localized in developing neurons of the sensory layer of the differentiating retina and in the developing brain. In adult tissues the expression of c-src was found to persist in certain cell types of the brain and the neural retina, especially in the bipolar cells of the inner nuclear layer, which are postmitotic, fully differentiated mature neurons. Thus c-src in Xiphophorus appears to be a developmentally regulated proto-oncogene which is important for neuronal differentiation during organogenesis, but whose persistence of expression in certain terminally differentiated neurons strongly suggests a particular maintenance function for c-src in these cells as well.

Animals↗

[The Duromedics mitral valve mechanical prosthesis: evaluation by means of transesophageal echocardiography].

We investigated via transesophageal echocardiography 29 patients with Duromedics mitral prosthesis to define the characteristics of normal and abnormal functioning valves as well as the advantages of this study compared to transthoracic echocardiography. The clinical and transthoracic examination identified three groups. The first group consisted of 8 patients with abnormal hemodynamic parameters (maximal velocity 245.5 +/- 38.4 cm/sec, maximal gradient 24.6 +/- 7.9 mmHg, medium gradient 9.8 +/- 0.8 mmHg, pressure half time 121.6 +/- 58.8 msec, valvular area 2.1 +/- 0.8 cm2). In 4 cases we detected a paravalvular regurgitant jet. The second group was formed of 12 symptomatic patients, with normal hemodynamic parameters (maximal velocity 169.1 +/- 20.1, maximal gradient 11.6 +/- 2.5, medium gradient 4.8 +/- 1.8, pressure half time 118 +/- 18 msec, valvular area 1.9 +/- 2.8 cm2). In 4 cases we detected a paravalvular regurgitant jet. The third group was formed by 9 asymptomatic patients with normal hemodynamic parameters: maximal velocity 160.6 +/- 26.6, maximal gradient 10.5 +/- 3.3, medium gradient 4 +/- 1, pressure half time 118 +/- 40, valvular area 2 +/- 0.5. We did not observe a regurgitant jet in any of these patients. Transesophageal echocardiography detected a paravalvular jet in all patients of the first group, with an area of 6.9 +/- 5.8 cm2; in the second group it demonstrated one or two valvular jets, with a maximal area of 5.1 +/- 3.2 cm2. Furthermore, it defined as valvular, the site of a jet previously described as paravalvular with the transthoracic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography↗

Progressive growth of fish tumors after transplantation into thymus-aplastic (nu/nu) mice.

The nude mouse does not reject xenografts of malignant and nonmalignant tissues of mammalian or avian origin, due to a deficiency of functional T-lymphocytes. In this study, tissue from a cold-blooded vertebrate, a teleost fish, was for the first time successfully transplanted to Swiss albino nu/nu mice. Malignant melanotic melanoma of Xiphophorus transplanted to nude mice showed progressive growth and could be serially passaged. In vitro culture experiments revealed that the fish tumor cells adapt to the physiological conditions of the mammalian host, most obviously to the body temperature. On the other hand, fish-specific morphological characters and biochemical features, e.g., expression of a melanoma-associated antigen, were retained. This experiment demonstrates the enormous capacity of the melanoma cells to adapt to severe changes in their environment, which even enables them to overcome the physiological barriers between such taxonomically distant vertebrate groups as fish and mammals.

Animals↗

A sex chromosomal restriction-fragment-length marker linked to melanoma-determining Tu loci in Xiphophorus.

In Xiphophorus, the causative genetic information for melanoma formation has been assigned by classical genetics to chromosomal loci, which are located on the sex chromosomes. In our attempts to molecularly clone these melanoma-determining loci, named Tu, we have looked for restriction-fragment-length markers (RFLMs) linked to the Tu loci. These RFLMs should be useful in obtaining a physical map of a Tu locus, which will aid in the cloning of the corresponding sequences. DNA samples from various Xiphophorus strains and hybrids including those bearing different Tu wild-type, deletion and translocation chromosomes, were screened for the presence of random RFLMs using homologous or heterologous sequences as hybridization probes. We find an EcoRI restriction fragment which shows limited crosshybridization to the v-erb B gene--but not representing the authentic c-erb B gene of Xiphophorus--to be polymorphic with respect to different sex chromosomes. Linkage analysis revealed that a 5-kb fragment is linked to the Tu-Sd locus on the X chromosome, a 7-kb fragment is linked to the Tu-Sr locus on the Y chromosome, both of Xiphophorus maculatus, and that a 12-kb fragment is linked to the Tu-Li locus on the X chromosome of Xiphophorus variatus. Using different chromosomal mutants this RFLM has been mapped to a frequent deletion/translocation breakpoint of the X chromosome, less than 0.3 cM apart from the Tu locus.

Animals↗

Preclinical and clinical results with an ultrasonic contrast agent.

In comparison to diagnostic radiology, ultrasound diagnostics has had no real contrast media. Theoretical considerations indicate that gas liquid systems seem to be favorable. The echocontrast agent SH U 454 is a system that releases minute gas bubbles that provide the contrast properties. Preclinical and clinical trials in more than 500 patients with right-heart lesions proved the efficacy and tolerance of the agent. Initial investigations showed that SH U 454 also may be useful in fields (eg, urology, gynecology) other than cardiology.

Adult↗

[Comparative randomized study of the effectiveness of intravenous recombinant tissue-type plasminogen activator and intravenous streptokinase in patients with acute myocardial infarct. Report of the European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator].

In a single-blind randomised trial in patients with acute myocardial infarction of less than 6 h duration, the frequency of coronary patency was found to be higher after intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA) than after intravenous streptokinase. 64 patients were allocated to 0.75 mg rt-PA/kg over 90 min, and the infarct-related coronary artery was patent in 70% of 61 assessable coronary angiograms taken 75-90 min after the start of infusion; 65 patients were allocated to 1,500,000 IU streptokinase over 60 min, and the infarct-related vessel was patent in 55% of 62 assessable angiograms. The 95% confidence interval of the difference ranges from +30 to -2% (p = 0.054). Bleeding episodes and other complications were less common in the rt-PA patients than in the streptokinase group. Hospital mortality was identical in the 2 treatment groups. At the end of the rt-PA infusion the circulating fibrinogen level was 61 +/- 35% of the starting value, as measured by a coagulation-rate assay, and 69 +/- 25% as measured by sodium sulphite precipitation. After streptokinase infusion, corresponding fibrinogen levels were 12 +/- 18% and 20 +/- 11%. In the rt-PA group only 4.5% of the fibrinogen was measured as incoagulable fibrinogen degradation products, compared with 30% in the streptokinase group. Activation of the systemic fibrinolytic system was far less pronounced with rt-PA than with streptokinase.

Adult↗

[Results and limits of fibrin-unspecific thrombolysis in acute myocardial infarct].

Acute myocardial infarction is caused by thrombotic occlusion of a coronary vessel. Mortality and quality of life are both determined by the extent of infarction. It is possible to interrupt the development of necrosis by early fibrinolytic therapy. If reperfusion is initiated within three to six hours, a significant reduction in mortality is likely. Currently available fibrin-unspecific plasminogen activators such as streptokinase and urokinase are effective thrombolytic agents but do not fulfill all the criteria of an ideal plasminogen activator. Recanalisation rates are relatively low after intravenous administration, since the agents are not fibrin-specific and because the effect is delayed. Serious hemorrhagic complications may occur, since therapeutically effective dosage results in a hemostatic defect. The possible advantages of reduction in blood viscosity for collateral circulation in the ischemic region and a possible antithrombotic effect have not been defined. A complex strategy is necessary for optimal treatment of acute myocardial infarction. Early intervention is decisive in regard to recanalisation rate, infarct size, left ventricular function and mortality, while delayed interventions serve to maintain the advantages of early recanalisation by limiting angina pectoris and preventing reinfarction. Therefore, a combination of early intravenous administration of a fibrinolytic agent with subsequent invasive intervention appears reasonable and advantageous. Progress in the treatment of acute myocardial infarction will depend on development of effective plasminogen activators capable of achieving rapid and complete recanalisation without major side effects after intravenous administration.

Coronary Circulation↗

Expression of proto-oncogenes in embryonic, adult, and transformed tissue of Xiphophorus (Teleostei: Poeciliidae).

In Xiphophorus the causative, primary cellular oncogene for melanoma formation has been assigned by classical genetics to a sex-chromosomal locus, designated Tu. Activation of Tu was proposed to be the result of the elimination of Tu-specific regulatory genes which normally suppress the transforming function in the non-tumorous state. In order to understand the role which known proto-oncogenes might play in this process, we have analysed the expression of src, erb A, erb B, ras, abl, sis and mil related genes from Xiphophorus during embryogenesis, in non-tumorous organs and in melanoma cells. For src, ras, erb B and sis a differential expression during embryogenesis and/or in normal organs was detected, with preferential expression of src in neural tissues, a high abundance of sis transcripts in an embryonal epitheloid cell line and of erbB transcripts in the head nephros. In melanoma cells ras, src and a v-erb B related gene were found to be expressed. The src gene most likely is more involved in secondary processes during tumor progression, while the expression of the v-erb B related gene might be transformation-specific because recently such a sequence was found to map to the close vicinity of the Tu-locus.

Animals↗

Expression of the c-src protooncogene in human skin tumors.

Retroviral oncogenes are genetic elements, the expression of which is responsible for the transformed phenotype of cells. These genes are derived from normal cellular DNA sequences called cellular protooncogenes, which are present in all human cells and seem to have potential transforming ability in tumors of nonviral origin, since it is possible that they undergo structural alterations and/or changes in their expression. Human skin tumors were analyzed in this study with respect to the expression of the c-src protooncogene, the cellular homologue of the Rous sarcoma virus transforming gene, by measuring the enzymatic activity of its gene product, the pp60c-src kinase activity. Tyrosine-specific kinase activity was detected in all skin tumors tested. The expression pattern of the c-src gene product in the melanomas tested was differential and varying kinase levels in different metastases from the same patient were detected. The elevation of kinase activity as compared to normal skin ranged from about 4- to 20-fold.

Adult↗

Comparative studies on the src proto-oncogene and its gene product pp60c-src in normal and neoplastic tissues of lower vertebrates.

1. Oncogenes appear to play an important role in the physiology of transformed as well as of normal cells. 2. The src oncogene is by far the most investigated oncogene in birds and mammals with respect to the biochemical characteristics of its tyrosine kinase activity, although the specific function of this enzymatic activity still remains to be uncovered. 3. Systematic studies on the src related kinase activity in lower animals are lacking. 4. To contribute to a better understanding of the function of the c-src gene, we performed a comparative study on lower chordates. 5. We were able to demonstrate the presence of c-src related sequences in Acrania, Cyclostomata, cartilagenous and bony fish. 6. By performing the pp60src-specific immune complex assay we detected a tyrosine specific kinase activity, that shows the same biochemical properties as the pp60c-src from higher vertebrates. 7. The level of kinase activity is regulated in an organ specific manner. 8. In lymphocystis tumors of flat-fish and in stomatopapilloma of freshwater eels a considerable amount of pp60c-src kinase activity was found, which, however, never exceeded the levels found in the normal brain.

Animals↗

Residual coronary stenosis after thrombolysis with rt-PA or streptokinase: acute results and 3 weeks follow-up.

Ninety-one patients with acute myocardial infarction were assigned to intravenous treatment with streptokinase or rt-PA as part of the randomized trial carried out by the European Study Group for Recombinant Tissue-Type Plasminogen Activator (rt-PA). A patent coronary artery was found in 37 of 45 (82%) patients treated with rt-PA and in 27 of 46 (59%) patients treated with streptokinase 75-90 minutes after start of infusion. Patients were subsequently anticoagulated with heparin or dicoumarol up to a repeat angiography 3 weeks after the infarction. Of the 64 patients with successful reperfusion, 3 died and 3 suffered reocclusion of the vessel. Quantitative analysis of the coronary stenosis both immediately after thrombolysis and at 3 weeks follow-up was possible in 33 cases. Residual stenosis (percentage narrowing of diameter) decreased from 74 +/- 14% to 56 +/- 17% (P less than 0.05). No difference was observed between the groups of patients treated with streptokinase (74 +/- 9% to 57 +/- 12%, N = 17) and with rt-PA (74 +/- 17% to 56 +/- 21%, N = 16). Despite the significant regression, a coronary stenosis of more than 50% of the diameter persisted in 82% of the patients three weeks after the infarction.

Cineangiography↗

Myocardial perfusion defects in contrast echocardiography: spatial and temporal localisation.

The position and size of experimental myocardial perfusion defects can be detected by using the echocardiographic contrast-medium Echoson together with digital image processing techniques. Video tapes showing the important sequences before, during and after cardial inflow of echo-enhancing agents are fed in total length into a digital image processing unit. The myocardial circumferences are then chosen interactively. All the frames are analysed and a synthetic picture is compiled, and shows the myocardial echo densities in a single, highly condensed form. Digital subtraction of blank values (condensed sequences before injection of contrast medium) greatly improves readability. Further concentration of the remaining information yields the following diagrams: flow/circumferential position (time summation); flow/time (position summation), which contain the desired information on homogeneity or defects of echo density against time and myocardial position.

Animals↗

Quantification of myocardial perfusion by contrast echocardiography.

Two-dimensional echocardiography allows identification of myocardial perfusion defects due to coronary artery occlusion by detection of regional wall motion abnormalities and absence of myocardial echocontrast enhancement after injection of echocontrast agents into the aortic root. In the current study twelve anesthetized closed chest dogs were examined before and after balloon occlusion of a coronary vessel. Size of perfusion defects was determined morphologically by Evans blue staining, while the circumferential extent of regional wall motion abnormality was calculated using radial wall motion analysis of the two-dimensional echocardiogram. Four mL of SH U 454 were injected into the aortic root for echocontrast studies. Perfusion defects in the echocardiogram were determined planimetrically in the analog two-dimensional echocardiographic image. In addition, perfusion defects in the contrast echocardiogram were estimated by a digital image processing technique along a circumferential mid-wall line. Along this line the time-intensity curves of the myocardial echocontrast were also calculated. There was a linear correlation between morphological determination of perfusion defects and their planimetric estimate in the contrast echocardiogram. The linear regression equation was y = 0.98x + 4.63, r = 0.92, and the standard error of estimate for the echocardiographic examination was SEE = 4.4%. Digital image processing did not increase accuracy in determining the size of perfusion defects (r = 0.88; y = 1.01x + 3.33; SEE = 5.7%). By comparing the extent of regional wall motion abnormalities with the size of anatomic perfusion defects there was a correlation of r = 0.85; SEE = 6.2%; y = 0.71x + 10.50.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Experimental studies of the evaluation of the size of infarct and perfusion defects using analysis of regional wall motion from 2-dimensional echocardiography].

In an experimental study with laboratory animals we studied the relation between the extent of a disorder of regional wall motion as determined by echocardiography and size of a perfusion defect following occlusion of a coronary vessel for 5 hours. It was demonstrated that wall motion is not uniform in a normal left ventricle and that there is a wide range of variability in wall motion within a given myocardial segment. For this reason we determined the extent of a disorder of regional wall motion in two echocardiographic planes with reference to defined normal values. Analysis of interobserver and intraobserver variability showed that reproducible determinations of the circumferential extent of a disorder of regional wall motion and the ejection fraction are possible with an acceptable degree of certainty. There was a significant correlation between morphological determinations of the size of a perfusion defect in the left ventricle and the circumferential extent of a disorder of regional wall motions as demonstrated in the echocardiogram (r = 0.83). The regression curve (y = 4.26 + 0.95x) for determinations of the size of the perfusion defect approached the identity line with a standard error of estimation for the echocardiographic examination of 7.4%. Size of the zone of infarction was overestimated by an average of 8% with echocardiography (r = 0.81), with a standard error of estimation of 6.6% (y = -2.41 + 0.85x). There was no significant correlation between ejection fraction and size of the perfusion defect or the size of infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Long-term results following therapy with streptokinase in myocardial infarct].

Long term results of thrombolytic therapy in myocardial infarction are determined primarily by the effects of treatment in the acute phase. Out of a total of 370 patients undergoing recanalization therapy, 170 consecutive patients were examined over a period of one to three years (mean 1.5 years) by means of ECG, exercise testing, thallium myocardial scintigraphy, radionuclide ventriculography, coronary angiography and contrast ventriculography. Frequency of chest pain, left ventricular function, reinfarction rate and mortality were analyzed. The patient cohort was divided into three subgroups: 1. patients with successful PTCR who underwent PTCA or bypass graft surgery; 2. patients with successful PTCR who were managed medically without subsequent reinfarction; 3. patients with definitive occlusion or reinfarction. Mortality in the hospital phase (within 30 days) was 4.9% in patients undergoing successful recanalization procedures as compared to 12.3% for patients with definitive occlusion. Late mortality at 1.5 years was 12.3% and 16.2%, respectively. These figures are similar to those found in the literature. In-hospital mortality is clearly reduced by early recanalization within 200 minutes of occlusion, and there is a reduction in the ultimate extent of infarction as well as improvement in left ventricular function. In order to prevent reocclusion (in 10 to 20% of cases) and reinfarction additional interventions such as PTCA or bypass grafting should be employed as soon as possible in suitable cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗