Search PubMed⌕ Search

Biomedical subjects

V Deutsch

Publications and source records attributed to V Deutsch.

At least 37 records · Page 2Linked to original sources

Growth inhibition of murine melanoma cells by antibodies to a cell surface glycoprotein implicated in retinoic acid action.

Previous studies have shown that treatment of S91-C2 murine melanoma cells with beta-all-trans-retinoic acid (RA) results in growth inhibition, enhanced activity of sialyltransferase, and increased glycosylation of a Mr 160,000 cell surface sialoglycoprotein (gp160). None of these effects could be detected in mutant clones (e.g., S91-C154) selected from the S91-C2 cells for resistance to RA-induced growth inhibition. These findings suggest that modulation by RA of gp160 might be related causally to growth inhibition. In this study we examined the possible role of gp160 in growth regulation using specific antibodies to this glycoprotein. Metabolic labeling of S91-C2 cells with either [3H]glucosamine or [35S]methionine revealed that the cells shed into the growth medium a gp160-like glycoprotein, in addition to several other macromolecules. The gp160-like glycoprotein was isolated from concentrated conditioned medium after preparative polyacrylamide slab gel electrophoresis in the presence of sodium dodecylsulfate by excision of the corresponding protein band. Rabbits were immunized with this material and immunoblotting revealed that their sera contained antibodies that bound specifically to gp160 in extracts of untreated or RA-treated S91-C2 cells. Indirect immunofluorescence staining followed by fluorescence-activated cell sorter analysis demonstrated that the anti-gp160 antibodies bound to the surface of both untreated and RA-treated S91-C2 cells and that the treated cells bound more of the antibodies than untreated ones. In contrast, these antibodies bound to the same extent to untreated and RA-treated resistant S91-C154 cells. The growth of S91-C2 cells in the presence of anti-gp160 antibodies in semisolid medium as well as in monolayer cultures was inhibited in a dose-dependent fashion. Fifty % growth inhibition was obtained at an immunoglobulin concentration of 10 micrograms/ml. The growth of cells exposed concurrently to RA and anti-gp160 antibodies was also inhibited strongly in semisolid medium, but the antibodies caused only a small increase in the inhibitory effect of RA in monolayer cultures. No inhibition by the antibodies of either anchorage-independent growth or anchorage-dependent growth of S91-C154 cells, grown in the absence or presence of RA, was observed. These results support the suggestion that cell surface gp160 might be involved in growth regulation in the S91-C2 cells.

Animals↗

Intracellular events following the infection of different cell types with vesicular stomatitis subviral particles.

Vesicular stomatitis virus (VSV) subviral particles (nucleocapsids and G-depleted particles) were used to infect various cells (chicken embryo, HeLa, and BHK21 cells). These particles bind to and penetrate into host cells; the association of G-depleted particles to cells was even better than that of normal virions. The parental genomes of subviral particles and virions were degraded at the same rate in the infected cells. Nevertheless, these subviral particles had a very low infectivity, synthesized very little viral macromolecules, and had very little, if any, effect on the various host cells used. Furthermore , subviral particles could be rescued in chicken embryo cells by uv-irradiated VSV virions, demonstrating that subviral particles actually penetrated into cells, and that their arrested cycle could be unblocked up to a certain point. On the other hand, subviral particles were not rescued in HeLa cells, suggesting a dependence on the host cell system.

Animals↗

Nongenetic complementation in VSV: asymmetric contribution of the L proteins of each parent in the rescue of group I ts mutants.

Complementation group I temperature-sensitive mutants of vesicular stomatitis virus (VSV) are rescued at nonpermissive temperature by UV-irradiated virus. Rescue is a nongenetic process mediated by the structural L protein molecules of the parental irradiated virus. This is shown by action spectra analysis (V. Deutsch, B. Muel, and G. Brun (1977), Virology 77, 294-305), efficiency of rescue at doses high enough to inactivate every gene I, and rescue by irradiated defective-interfering short particles. Viral molecular synthesis at 39.6 degrees using the ts genomes as templates and stimulated by UV-irradiated virus is shown by gel electrophoresis of rescued virion proteins. Parental strain ts 053(I) is thermolabile in vitro while the thermostability of the rescued virions, genetically characterized as ts group I virus, is identical to that of helper wt or ts+ revertant. This suggests that some parental Lwt molecules are reincorporated in the rescued virions, together with newly synthesized Lts molecules. Efficiency variation of the rescue as a function of the multiplicity of infection of the UV-irradiated virions depends on the m.o.i. of the unirradiated ts I mutants. This result suggests that rescue depends on the concentration of the helper L molecules and also of that of the L initially bound to the ts template. That L of both parents contribute to rescue is supported by the observations that (1) rescue by UV-wt is strongly diminished after in vitro heating of thermolabile ts O53(I). (2) Intragenic rescue can be demonstrated: The helper activity of a given UV-ts I mutant is different according to the unirradiated ts I mutant used; the activity of helper L associated with different templates in intragenic heterologous combinations is higher or lower than its activity in the homologous combination (self-rescue control), instead of being equal as expected. (3) Efficiency of rescue by UV-wt also varies according to the ts I mutant. The initially bound Lts seems therefore to play a role important and different from that of the helper L. Contribution of both parent L to rescue seems thus to be qualitatively different.

Animals↗

Stimulation of sialyltransferase activity of melanoma cells by retinoic acid.

Retinoic acid (RA) treatment of murine S91-C2 melanoma cells has been found to augment the activity of glycoprotein: sialyltransferase in a dose-dependent and time-dependent process. The enzymatic activity in cells treated with 10 microM RA reached a maximal level, 3-fold higher than in untreated cells, 72 h after initiation of treatment. In contrast, the addition of RA directly into the reaction mixture had no stimulatory effect on sialyltransferase. The endogenous glycoproteins to which sialic acid is transferred from cytidine monophosphate (CMP)-[14C] sialic acid by the action of sialyltransferase have been identified by fluorography after polyacrylamide gel electrophoresis. One of these acceptors, a glycoprotein of Mr 160 000, comigrated in gel electrophoresis with a cell surface sialoglycoprotein that can be labeled by the periodate-tritiated borohydrate procedure more intensely on intact RA-treated than on untreated cells. Removal of sialic acid residues exposed on the surface of either control or RA-treated cells enhanced 2- to 3-fold the transfer of sialic acid to endogenous acceptors. These results suggest that the increased sialyltransferase activity in RA-treated melanoma cells may be responsible for the enhanced sialylation of certain cell surface glycoproteins. RA treatment of several other tumor cell lines also resulted in stimulation of sialyltransferase activity indicating that this effect of RA is not limited to the S91-C2 melanoma cells.

Animals↗

Criss-cross heart--a case with horizontal septum, complete transposition, pulmonary atresia and ventricular septal defect.

Criss-cross heart is a recently described anomaly in which the systemic and pulmonary blood streams cross at the atrioventricular (AV) level, without mixing. A case of criss-cross heart is described in which the right atrium, in a solitus position, communicated with a left-superior positioned, morphologically right ventricle, and the left atrium communicated with a normally located, morphologically left ventricle. The interventricular septum occupied a horizontal plane. Associated defects were complete d-transposition of the great arteries with l-positioned aorta, pulmonary atresia, ventricular septal defect, atrial septal defect, and patent ductus arteriosus. To the best of our knowledge this is the first angiocardiographic demonstration of this rare combination of lesions. The literature on criss-cross heart and horizontal septum is reviewed. It is stressed that regardless of whether the criss-cross phenomenon is an anatomical fact or an angiocardiographic illusion, it is an established angiocardiographic entity and should be recognized as such.

Angiocardiography↗

"Complete-transposition-like" coronary arterial pattern in single ventricle with inverted infundibulum and transposition of the great arteries.

In 19 out of 28 cases of single ventricle with inverted infundibulum and 1-transposition of the great arteries the right coronary artery arose from the posterior aortic sinus, the right anterior aortic sinus being the noncoronary one. This coronary arterial pattern was described before only in association with d-transposition of the great arteries. We suggest that angiocardiographic demonstration of this coronary arterial pattern in association with an 1-positioned aorta favors the diagnosis of single ventricle.

Angiocardiography↗

Interruption of the aortic arch with complete transposition of the great arteries. Clinical and angiocardiographic diagnosis at the age of one day.

The association of complete transportation of the great arteries and complete interruption of the aortic arch is very rare. This combined lesion was diagnosed clinically in a 1-day-old infant in whom it caused cyanosis of the upper half of the body. The diagnosis was confirmed angiocardiographically. We believe this is the youngest patient in whom this diagnosis was made in vivo.

Aorta, Thoracic↗

Uninterrupted inferior vena cava with azygos continuation.

Azygos continuation of the inferior vena cava is diagnosed in infants in the presence of obstruction to flow in the inferior vena cava due to infrahepatic interruption. Recently we studied in an infant complex congenital heart disease in which there was azygos continuation of the inferior vena cava without infrahepatic interruption or any other obstructive lesion of this vessel. The blood from the lower part of the body drained into the right atrium by two wide patent veins: the inferior vena cava and the azygos system. The angiocardiographic observations of this condition in an infant are reported for the first time to our knowledge, and the embryologic development is briefly reviewed.

Azygos Vein↗

Exercise tests in patients with severe angina pectoris: an angiographic correlation.

Graded submaximal ergometric tests were peformed on 60 patients who suffered from clinically severe angina pectoris, and the results were correlated with their coronary angiograms. The test was positive in 44, negative in 9, and undetermined in 7 patients (defined as failure to reach the target heart rate without ischemic ST changes). Among patients with positive tests, 42 (95%) had obstruction of one to three coronary vessels. Among patients with negative tests, only 3 had significant coronary disease (sensitivity 93%). While all patients suffered clinically from severe "angina pectoris," 8 (15%) had insignificant CAD, and among them 6 had a negative and 2 a false-positive exercise response (specificity 75%). Although ST depression was a good indicator of CAD, its degree did not parallel the severity of the lesions. The peak heart rate on exercise of patients with ischemic ST changes was lower than their target heart rate, suggesting that the heart rate at which ST changes occur constitutes in itself a good indicator of severity. Among the 7 patients with undetermined tests, CAD was found in 6. In these patients the absence of ST changes may be ascribed to extensive myocardial fibrosis, and the only clue to CAD resides in the negative chronotropic response to exercise. Although exercise testing does not always distinguish between normal and CAD patients, it nevertheless constitutes a valuable noninvasive technique for the detection of the high-risk patients.

Adult↗

Supravalvular aortic and peripheral pulmonary arterial stenoses. A report of eight cases in two generations.

Peripheral pulmonary arterial stenosis, either alone or in combination with supravalvular aortic stenosis, is described in two generations of one family. The last child born in the first generation ws the only fatal case and showed severe narrowing and thrombosis of the pulmonary arteries and significant narrowing of the descending aorta. Physical and mental development were normal in the seven surviving patients. Five had slight dyspnea on effort. Hemodynamic and angiocardiogrphic studies showed multiple peripheral pulmonary stenosis in six patients and supravalvular aortic stenosis or aortic hypoplasia in the last three of the first generation and in one of the second generation. The younger children were more severely affected. A marked systolodiastolic caliber variation of the main pulmonary arteries was noted angiographically in all those studied. We suggest that this finding can be used as an indirect sign of the presence of peripheral pulmonary arterial stenosis.

Aortic Valve Stenosis↗