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Biomedical subjects

M Schartl

Publications and source records attributed to M Schartl.

At least 163 records · Page 9Linked to original sources

Elevated expression of the cellular src gene in tumors of differing etiologies in Xiphophorus.

In the fish Xiphophorus we have detected elevated levels of pp60c-src kinase activity in a variety of tumors (n = 34) of neurogenic, epithelial, and mesenchymal origin either of hereditary etiology or induced by carcinogens. This elevation ranged from 2-fold up to 50-fold compared to the corresponding non-tumorous tissue and up to 6-fold compared to the highest activities found in any of the normal organs. The level of elevation parallels the degree of malignancy in melanoma and in tumors of mesenchymal origin. In fish bearing tumors of hereditary etiology kinase activity was also elevated in the non-tumorous brain, while in fish bearing induced tumors, kinase activity was elevated only in the cells of the neoplasia.

Animals↗

Hemodynamic effects of molsidomine, isosorbide dinitrate, and nifedipine at rest and during exercise.

In the first study the hemodynamic effects of standard doses of molsidomine (2 mg intravenously), isosorbide dinitrate (ISDN) (5 mg sublingually), and nifedipine (20 mg sublingually) were assessed at rest and under exercise conditions in a group of 30 patients with coronary heart disease. With the patients at rest both molsidomine and ISDN were associated with prompt reductions in left ventricular end-diastolic pressure and mean pulmonary artery pressure, whereas nifedipine was associated with slight reductions in left ventricular end-diastolic pressure and mean pulmonary artery pressure that did not attain statistical significance. Nifedipine and ISDN caused a decrease in mean aortic blood pressure, which resulted in a reactive increase in heart rate that was only significant with nifedipine. After administration of molsidomine, there was no significant change in mean aortic pressure at rest. There were reductions in stroke volume index and cardiac index after administration of molsidomine and ISDN. Nifedipine, however, was associated with significant increases in stroke volume index and cardiac index. None of the three test substances caused changes of contractility parameters. Under exercise conditions reductions in left ventricular end-diastolic pressure, mean pulmonary pressure, and mean aortic pressure were documented following administration of molsidomine, ISDN, and nifedipine. There were no major changes in maximum heart rate or stroke volume index during exercise with any of the three drugs. However, nifedipine was associated with a significant increase in cardiac index, whereas molsidomine and ISDN produced no major changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparative studies on the ultrastructure of malignant melanoma in fish and human by freeze-etching and transmission electron microscopy.

Malignant melanomas (MM) in the fish Xiphophorus and in humans were studied both by transmission electron microscopy (TEM) and freeze-etching (FE). In both fish and human melanomas the cells show interdigitations of the plasma membranes. The nuclei are large and lobulated and have many nuclear pores. Melanosomes are abundant and melanosome complexes ("compound melanosomes") occur regularly. Pinocytotic vesicles could be demonstrated in fish and human melanomas showing local differences in frequency and distribution patterns in the tumor. Intercellular junctions are lacking in MM cells from fish and humans. The FE technique showed considerable advantages in demonstrating membrane-surface peculiarities such as nuclear pores or pinocytotic vesicles. The FE replicas of fish melanomas are like those of humans. These findings may support the hypothesis that melanoma in fish and humans reflect the same biological phenomenon.

Animals↗

Differential expression of the cellular src gene during vertebrate development.

Cellular genes that are homologous to the transforming genes of certain RNA tumor viruses are suspected to play a functional role during normal developmental processes. To investigate this further, we are studying the expression of the cellular homolog of the Rous sarcoma virus transforming gene (c-src) during embryogenesis of fish, frog, and chicken by quantitative determination of the activity of the c-src encoded protein kinase (pp60c-src). The kinase activity from embryos of fish, frog, and chicken displays the same enzymatic characteristics as the kinase from adult animals: It phosphorylates only tyrosine residues in protein substrates, and its activity is relatively insensitive to inhibition by the diadenosine nucleotide Ap4A. During the course of development, the varying kinase activity level reflects differential expression of the c-src gene product. The kinase activity is low during early development, increases dramatically during organogenesis, and decreases thereafter to the level found in adult animals. The kinase activity displays an organ specificity, with brain showing the highest activity in embryos as well as in adults. Muscle, however, shows high activities during organogenesis, but no or barely detectable activity in adult animals. Our data suggest, therefore, that the c-src gene product plays more of a role in differentiation than in proliferation processes during embryogenesis, and that it may act as a pleiotropic effector.

Amino Acids↗

Cellular src gene product detected in the freshwater sponge Spongilla lacustris.

Serum from Rous sarcoma virus tumor-bearing rabbits immunoprecipitated from extracts of the freshwater sponge Spongilla lacustris a tyrosine-specific protein kinase with characteristics similar to the chicken pp60c-src kinase activity. An immune competition assay confirmed the relationship between the protein from sponges and viral pp60v-src.

Animals↗

Xiphophorus as an in vivo model for studies on oncogenes.

The capacity of Xiphophorus to develop neoplasia can be formally assigned to a "tumor gene" (Tu), which appears to be a normal part of the genome of all individuals. The wild fish have evolved population-specific and cell type-specific systems of regulatory genes (R) for Tu that protect the fish from neoplasia. Hybridization of members of different wild populations in the laboratory followed by treatment of the hybrids with carcinogens led to disintegration of the R systems permitting excessive expression of Tu and thus resulting in neoplasia. Certain hybrids developed neoplasia even spontaneously. Observations on the genuine phenotypic effect of the derepressed Tu in the early embryo indicated an essential normal function of this oncogene in cell differentiation, proliferation and cell-cell communication. Tu appeared to be indispensable in the genome but may also be present in accessory copies. Recently, c-src, the cellular homolog of the Rous sarcoma virus oncogene v-src, was detected in Xiphophorus. The protein product of c-src, pp60c-src, was identified and then examined by its associated kinase activity. This pp60c-src was found in all individuals tested, but, depending on the genotype, its kinase activity was different. The genetic characters of c-src, such as linkage relations, dosage relations, expression, etc., correspond to those of Tu. From a systematic study which showed that pp60c-src was present in all metazoa tested ranging from mammals down to sponges, we concluded that c-src has evolved with the multicellular organization of animals. Neoplasia of animals and humans is a characteristic closely related to this evolution. Our data showed that small aquarium fish, besides being used successfully because they are time-, space-, and money-saving systems for carcinogenicity testing, are also highly suitable for basic studies on neoplasia at the populational, morphological, developmental, cell biological, and molecular levels.

Animals↗

[Quantification of myocardial perfusion defects using 2-dimensional contrast echocardiography].

Ten closed-chested beagles were employed to determine whether reproducible echocontrast imaging of the myocardium could be obtained following injection of the new ultrasonic contrast medium Echocon into the aortic root, and whether myocardial perfusion defects could be successfully diagnosed by this method. The change in intensity of contrast in the myocardium was measured by videodensitometry simultaneously in the supply areas of the left anterior descending and left circumflex branches of the left coronary artery before and during occlusion of the circumflex branch by means of a balloon catheter. Injection of Echocon into the aortic root led to reproducible echocontrast imaging of the entire myocardium. The occlusion of the circumflex branch caused a significant reduction (p less than 0.01) in intensity of contrast in the supply area of the circumflex branch, whereas no differences by comparison with the starting values were identifiable in the supply area of the left anterior descending branch. The correlation factor between the sizes of the perfusion defects ascertained by echocardiography and by planimetric measurement using a pathological anatomical approach was found to be r = 0.89. The injection of Echocon into the aortic root did not induce any significant changes in the aortic or pulmonary pressure, or in heart rate. Only slight flattening of the T-waves, which never lasted longer than 15 seconds, was observed in 50% of the animals. Contrast echocardiography of the myocardium could thus contribute to the diagnosis of coronary heart disease, i.e. perfusion defects.

Animals↗

[The value of two-dimensional echocardiography in the diagnosis of acute transmural primary infarctions].

The validity of two-dimensional echocardiography (2 DE) in the diagnosis of evolving myocardial infarction was assessed in 123 patients with a suspected acute myocardial infarction (chest pain for less than 4 hours). 84 patients developed a myocardial infarction, 39 did not. Detection and extent of a regional wall motion disorder in 2 DE were compared to ECG, enzymes, hemodynamics, coronary angiography and clinical data. The reliability of ECG and 2 DE in the diagnosis of acute myocardial infarction was found to be similar: sensitivity 89% for 2 DE, 96% for ECG; specificity 89% vs (= versus) 73%; positive predictive value 95% vs 89%; negative predictive value 79% vs 90%. This means that in most cases the ECG is a sufficient and reliable method in detecting or excluding acute myocardial infarction. Because of the equipment needed, the limited practicability and because of specific problems (distinction between new and old infarction), the 2 DE should be regarded as a supporting method to the ECG but not as an essential one in the diagnosis of acute myocardial infarction. The possible benefit of echocardiographic examination is the identification of high risk patients by non-invasive determination of the size of infarction. There was a significant correlation between the extent of wall motion disorder and the maximum CK levels as well as the incidence of cardiac complications such as hypotension, pulmonary congestion, and ventricular arrhythmias.

Acute Disease↗

[Computer tomographic and echocardiographic diagnosis of intracardial space occupying masses].

Nineteen patients suspected of having intracavitary masses were examined by echo-cardiography and computer tomography. One 1 cm. thrombus on the mitral valve could be demonstrated only on the echo-cardiogram and was interpreted as a tumour. Both CT and echo-cardiograms produced occasional false negative findings with cardiac thrombi, which were ultimately diagnosed by the other method or by ventriculography. Differentiation between a thrombus and a tumour depends essentially on its localisation and on the history, and some morphological criteria. Echo-cardiography and densitometric measurements did not assist in the differential diagnosis. CT may be able to differentiate thrombus from tumour if the latter contained fat or has become cystic.

Adult↗

[Diagnosis of intracardial and paracardial space-occupying masses: comparison between two-dimensional echocardiography and computed tomography].

The validity of two-dimensional echocardiography (2-D echo) and computed tomography (CT) in the detection of intra- and paracardial tumors and thrombi was compared in 32 patients: 7 endocardial myxomas, 1 left ventricular fibroma, 2 paracardial cysts, 1 paracardial tumor, and 21 thrombi. In 16 cases intraoperative findings served as a control. The 2-D echo is easier to handle and free of radiation of contrast media. CT can visualize cardiac tumors independently of their location, whereas 2-D echo sometimes insufficiently images paracardial and right ventricular structures. It must be considered an advantage that 2-D echo detects mobile tumors such as those attached to valves, which the CT will not show. The tissue involved is more likely to be characterized by CT, although results are unreliable. However, in all cases tumors could be differentiated from thrombi by means of additional diagnostic criteria, such as the pattern of wall motion or valve motion. 2-D echo and CT therefore appear to be complementary methods rather than competitive ones. Invasive diagnostic procedures are required only to answer particular questions, e.g., concerning the coronary arteries.

Cysts↗

[Relation between late potentials, ventricular arrhythmias, left ventricular dysfunction and occlusion time following intracoronary thrombolysis].

25 patients who had undergone intracoronary thrombolysis (ICT) during acute myocardial infarction were studied an average of 9.8 months after the event in order to test the effect of the procedure on the incidence of complex ventricular tachyarrhythmias, late potentials determined by the signal-averaging technique, ejection fraction, and left ventricular asynergy. The relationships between these findings were tested. ICT was successful in 17 patients. There was a statistically significant relationship (p less than 0.05) between demonstrable akinesia and dyskinesia, late potentials, and complex ventricular tachyarrhythmias. Akinesia and dyskinesia and complex tachyarrhythmias were found more often in the 8 patients in whom ICT was unsuccessful than in the remaining 17 subjects (p less than 0.05). In the latter group no relationship was found between duration of occlusion and the incidence of asynergy, complex tachyarrhythmias, and late potentials; occlusion time was more than 200 min in 7 patients and less than 200 min in 10 patients. It is desirable to hold occlusion time below 200 min if there is no collateral circulation to the jeopardized myocardium.

Arrhythmias, Cardiac↗

The expression in eukaryotes of a tyrosine kinase which is reactive with pp60v-src antibodies.

All specimens of Eumetazoa and Parazoa, ranging from mammals, birds, teleosts, sharks, lampreys, amphioxus, insects, down to sponges showed the pp60c-src associated kinase activity, indicating that c-src, which is the cellular homologue of the oncogene v-src of Rous sarcoma virus (RSV) is probably present in all multicellular animals. Protozoa and plants did not show pp60c-src kinase activity. The degree of c-src expression depends on the taxonomic rank of the Eumetazoa tested, and is organ-specific with nervous tissues displaying the highest kinase activities. In the central nervous system of mammals and birds we found a high c-src expression, and in that of the lampreys, amphioxus, and insects the lowest. Unexpectedly, total extracts of sponges showed an amount of pp60c-src kinase activity similar to that of brain cell extracts of mammals and birds. These findings suggest that pp60c-src is a phylogenetic old protein that might have evolved together with the multicellular organisation of Metazoa, and that might be of importance in proliferation and differentiation of nontransformed cells.

Animals↗

Correlations of inheritance and expression between a tumor gene and the cellular homolog of the Rous sarcoma virus-transforming gene in Xiphophorus.

Neoplastic transformation of pigment cells in the teleostean fish Xiphophorus is mediated by a cellular oncogene (Tu). Normally. Tu is suppressed by multiple regulating genes (R). Depending on impairment and loss of R genes, Tu is permitted to express itself phenotypically. In the pigment cell system, different degrees of Tu expression lead to small spots of transformed cells or to benign or malignant melanoma. All neoplastic and nonneoplastic cells of all Xiphophorus genotypes tested thus far appear to contain the cellular homolog (c-src) of the avian sarcoma virus oncogene (v-src). The evidence for this stems from the detectability of a Mr 60,000 phosphoprotein with associated kinase activity (pp60c-src) that reacts with antiserum against viral pp60src. We followed the inheritance of Tu (identified by spots and melanomas) compared to the expression of c-src identified by the pp60c-src-associated protein kinase). By quantitative determination of kinase activity in immunoprecipitated pp60c-src from fish showing different degrees of Tu expression, we have investigated whether there exists a correlation between the expression of c-src and Tu. In genotypes with the same genetic background, cells from Tu-containing fish express more pp60c-src than do cells from fish lacking Tu. In genotypes carrying a Tu gene and which show differences in the amount of gene expression due to a different extent of repression by regulating genes, analysis of kinase activity revealed that an increase of Tu expression is correlated with an elevated level of pp60c-src-associated kinase activity. Our findings may indicate that c-src activity in Xiphophorus is modulated by the Tu gene product or that Tu and c-src are regulated coordinately.

Animals↗

[Changes of regional blood volume after the application of nitroglycerin measured by functional whole-body scanning (author's transl)].

After in-vivo labeling of red blood cells with 99mTc, the radioactivity of different parts of the body is proportional to the regional blood volume. The pharmacologically caused changes of the local blood volume can be examined simultaneously in different regions of interest by functional whole-body scanning. By this technique the effect of nitroglycerin on the distribution of blood volume was investigated in 10 patients with coronary artery disease. After nitroglycerin administration we found a statistically significant diminution of blood volume over the heart, the great intrathoracal vessels, and the liver. Furthermore, there was a distinct increase of local blood volume in th legs and the arms.

Abdomen↗