Search PubMed⌕ Search

Biomedical subjects

A Bloch

Publications and source records attributed to A Bloch.

At least 109 records · Page 6Linked to original sources

Differentiation-associated changes in human non-T, non-B leukemia cell lines after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA).

The ability of TPA to induce stable phenotypic changes that normally serve as markers of differentiation was examined in the four human non-T, non-B cell lines, NALL-1, NALM-16, REH and KM-3. In all four lines, noncytotoxic concentrations of the phorbol ester caused an extensive reduction in the number of cells expressing cALL surface antigen and terminal deoxynucleotidyl transferase. The disappearance of these markers correlated with the loss of cell proliferation. In one of the cell lines, NALL-1, TPA treatment gave rise to a significant increase in Ia-like antigen and antigen T-101, markers which represent more advanced stages of cell maturation. However, surface or cytoplasmic immunoglobins, indicators of mature B cells, were not detectable. Antigen 3A1, specific for myeloid and for T cells, antigen Leu-4, specific for T cells and antigen CM1, specific for monocytes, were also absent. In all cell lines, exposure to TPA resulted in an approximately two-fold increase in acid phosphatase and beta-glucuronidase activity. The emergence of these phenotype changes was not altered upon repeated washing of the TPA-treated cells. These results demonstrate that while TPA is capable of inducing various non-T, non-B cell lines to differentiate to a limited degree, differences exist between the lines in the extent to which they can mature towards the B-cell stage.

Acid Phosphatase↗

Early decline in c-myb oncogene expression in the differentiation of human myeloblastic leukemia (ML-1) cells induced with 12-O-tetradecanoylphorbol-13-acetate.

The relationship of oncogene expression to proliferation and differentiation has been examined in a line of human myeloblastic leukemia (ML-1) cells. Proliferating leukemic cells were found to express a 4.3-kilobase cellular homologue (c-myb) of the transforming sequence of avian myeloblastosis virus. A rapid decline in the expression of this transcript was seen in cells induced to differentiate with 12-O-tetradecanoylphorbol-13-acetate. The level of c-myb RNA was decreased by greater than 50% as early as 3 hr after 12-O-tetradecanoylphorbol-13-acetate exposure, and at 8 to 72 hr the reduction was greater than or equal to 4-fold. Subsequent to the decrease in oncogene expression at 3 hr, DNA synthesis began to decline; by 24 hr, cell proliferation had ceased. At this time, monocyte- and macrophage-like cells were beginning to emerge. These findings demonstrate that c-myb is expressed during ML-1 cell proliferation and declines prior to the loss of DNA synthesis that accompanies the differentiation process.

Cell Differentiation↗

[Echocardiographic and electrocardiographic evaluation of the effects of propranolol and verapamil in obstructive hypertrophic cardiomyopathy].

The purpose of this study is to compare M-mode echocardiographic and electrocardiographic modifications obtained by short-term therapy (6 weeks) with high doses (480 mg/day) of propranolol or verapamil in six patients with hypertrophic obstructive cardiomyopathy. Propranolol prevents heart rate acceleration and reduces significantly the echocardiographic obstruction index during provocative testing with isoprenaline, when verapamil doesn't. However verapamil seems to be more able than propranolol to suppress ventricular arrhythmias as demonstrated in Holter monitoring. Evaluation of each patient suffering from hypertrophic obstructive cardiomyopathy with echocardiography and 24-hours electrocardiography would permit to better define appropriate therapy.

Adult↗

[The value of echocardiography in ambulatory practice. A 2 year follow up].

Echocardiography plays an important role in diagnostic methods in cardiology, but its real contribution to ambulatory practice has still not been defined. For this reason, we have reviewed all the echocardiograms (echo) recorded during 1979 on non-hospitalized subjects at the echo laboratory of the cardiology center at the Geneva University Hospital. From a questionnaire answered by the physicians approximatively two years after the echo recording, follow-up of the patients and clinical impact of the method have been analyzed. 220 adult patients have had an M-mode echo, 70 of them have also had a two-dimensional echo. The follow-up of 141 patients has been analyzed. Contribution to diagnosis related to the clinical indication: Group I "precise cardiopathy": well defined cardiological diagnosis obtained by the physician (152 patients). The clinical diagnosis was confirmed in 25.5 p. 100 of the patients, diagnosis was quantitatively completed in 19 p. 100 of the patients, it was partially or totally unconfirmed in 53 p. 100 of the patients. Group II "cardiopathy X": cardiac lesion suspected, but clinically not identifiable (48 patients). The echo allowed a precise diagnosis in 12.5 p. 100 of the patients, but it showed non classifiable anomalies in 25 p. 100, normal recordings in 60.5 p. 100, and technical failures in 2 p. 100 of the patients. Group III "controls": precise diagnosis already know (20 patients). The echo supplied a quantitative complement in 19 patients and allowed a new diagnosis in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗

Macromolecular and cell cycle effects of different classes of agents inducing the maturation of human myeloblastic leukemia (ML-1) cells.

The effect of various classes of differentiation-inducing agents on macromolecular synthesis was studied in a human myeloblastic leukemia cell line (ML-1). Antineoplastic drugs such as 1-beta-D-arabinofuranosylcytosine, daunorubicin, and actinomycin D caused early inhibition of DNA synthesis, which generally preceded the accrual of differentiation markers. In contrast, retinoic acid and conditioned medium from mitogen-stimulated leukocytes caused a delayed decline in DNA synthesis, which accompanied the appearance of maturing morphology. With 12-O-tetradecanoylphorbol-13-acetate, the decline in DNA synthesis was temporally linked to the onset of maturation, and this agent evidenced some properties of both the antineoplastic agents and the more physiological inducers, retinoic acid and conditioned medium. Antineoplastic agents and conditioned medium, when applied simultaneously, induced differentiation in an additive or synergistic manner, simulating the effects of 12-O-tetradecanoylphorbol-13-acetate. RNA and protein synthesis continued during maturation induced with all these agents, although a partial reduction in RNA synthesis was observed at later time points (greater than or equal to 24 hr). Agents incapable of inducing differentiation, such as cordycepin and cycloheximide, were characterized by a lack of sustained inhibition of DNA synthesis and/or by early (3 hr) inhibition of RNA or protein synthesis. The decline in DNA synthesis caused by the inducing agents was accompanied by decreased cell cycle progression, cells accumulating largely in G1 phase. With daunorubicin and actinomycin D, block of the G1-S transition was evident at 24 hr, whereas with conditioned medium and retinoic acid, accumulation in G1 occurred in a progressive fashion, greater than 77% of cells residing in this phase on Day 6. Maximal inducing doses of 12-O-tetradecanoylphorbol-13-acetate (greater than 80% differentiation) caused an accumulation of cells in G1, as well as an accumulation of cells with a G2-M-phase DNA content (approximately 40%). These observations indicate that early inhibition of DNA synthesis, with sparing of RNA and protein synthesis, is characteristic of the differentiation-inducing antineoplastic drugs examined. These agents may induce differentiation by inhibition of the proliferation path, whereas conditioned medium and retinoic acid may act by the stimulation of differentiation paths. Differentiation can be enhanced by the simultaneous application of agents targeting both of these paths.

Cell Cycle↗

[One- or two-dimensional echocardiography. A comparative study].

A consecutive series of 300 M-mode and two-dimensional echocardiograms was reviewed retrospectively by 2 independent observers. These tests had been performed in adult patients who were either ambulatory or hospitalized in a community hospital. The diagnostic contribution of two-dimensional echo in comparison to M-mode was nil in three-quarters of the cases; it was rated as important or essential in only 20% of the cases. It is concluded that M-mode echocardiography in adults retains its value in everyday cardiac practice.

Adult↗

Differential ability of mitogen-stimulated human leukocyte-conditioned media to induce Fc receptors in human leukemia cells.

The ability of mitogen-stimulated human leukocyte-conditioned media (M-CM) to induce the in vitro differentiation of various human leukemic cell lines was evaluated by measuring the appearance of Fc receptors (FcR) through their ability to form EA rosettes. Only cells of myeloid lineage were induced by M-CM to express FcR; T-, and B-, and non-T/non-B cells failed to respond. As determined with ML-1, a line of human myeloblastic leukemia cells, pokeweed mitogen-conditioned medium, at concentrations of 1-10%, stimulated the expression of FcR in 70-98% of the cells within 1 day after treatment. Phytohemagglutinin-, concanavalin A-, and lipopolysaccharide-conditioned media were less active. The FcR-inducing activity was partially separated from M-CM by chromatography on Sephadex G-75. It was stable between pH 4 and 10, and lost activity at temperatures above 40 degrees C.

Cell Line↗

Different hemodynamic actions of trinitroglycerin and isosorbide dinitrate in patients with acute myocardial infarction.

The hemodynamic effects of intravenously administered trinitroglycerin (TNT) and isosorbide dinitrate (ISDN) in stechiometric equivalent doses were studied in 30 patients with acute myocardial infarction. Both drugs were given over 30 min in every patient, and the stability of the condition of the patient was checked by administering the initial drug again. Measurements were made by right heart catheterization using a balloon tip thermodilution catheter and a catheter in the radial artery. TNT and ISDN have different hemodynamic effects. By multivariate analysis it could be shown that TNT is a venous dilator, lowering mainly pulmonary capillary pressure, while ISDN acts more as a mixed vasodilator, diminishing mainly peripheral vascular resistance and increasing cardiac output. These drugs have, therefore, a different spectrum of indications in patients with acute myocardial infarction.

Cardiac Output↗

[Hemodynamic effects of intravenous isosorbide dinitrate in acute myocardial infarct].

The hemodynamic effects of intravenous isosorbiddinitrate (ISDN) were studied in 15 patients with acute myocardial infarction. Pressure and flow parameters were measured by right heart and radial catheterization and by the thermodilution method. 3-9 mg/hour ISDN was infused intravenously and the hemodynamic values were measured during half an hour in clinically stable state. The statistical analysis was carried out by paired Student's t-test and factors analysis. After ISDN therapy 10 patients showed a significant fall in pulmonary capillary pressure (-24%), 9 a rise in stroke volume index (+21%) and cardiac index (+13%). Two patients only exhibited a rise in pulmonary capillary pressure (+10%) and one a fall in cardiac index (-5%). ISDN changes in pulmonary capillary pressure, stroke volume and cardiac output were mainly due to changes in pulmonary and systemic vascular resistances and much less to those in the systemic venous bed. It can be supposed that intravenous ISDN behaves more like a mixed than a venous vasodilator and can be recommended for acute myocardial infarction patients with high pulmonary capillary pressure and low cardiac output.

Adult↗

[Physical and psychological future of patients with coronary disease. To whom should ambulatory rehabilitation be proposed? (author's transl)].

To ambulatory rehabilitation programme was proposed to 91 patients during their stay in hospital for myocardial infarction or aortocoronary bypass surgery. A retrospective study showed that 51 patients did follow the programme, whereas 40 patients preferred their own method of self-rehabilitation. Serial exercise tests demonstrated progressive and considerable improvement in physical aptitude among those who followed the programme, but the psychological, socio-familial and professional outcome was globally the same in both groups. The present study therefore confirms the numerous advantages of the rehabilitation programme but also shows that many of the potential candidates to such programmes are capable of returning by themselves to a normal and active life.

Ambulatory Care↗

Synthesis and biological evaluation of 6-ethynyluracil, a thiol-specific alkylating pyrimidine.

6-Ethynyluracil (3) was prepared by two different synthetic procedures. In one approach, 6-formyluracil was reacted with (dibromomethylene)triphenylphosphorane to give 6-(2,2-dibromovinyl)uracil (2), which was silylated and treated with phenyllithium to yield 3. Alternatively, silylated 6-iodouracil was reacted with trimethylsilylacetylene in dry triethylamine in the presence of a palladium/copper catalyst to give 6-[(trimethylsilyl)ethynyl]uracil (5). Compound 5 was converted to 3 in refluxing methanol. At neutral pH, 3 reacted with thiols, such as glutathione, 2-mercaptoethanol, and L-cysteine, but did not react with glycine or L-lysine. This reaction was accompanied by a shift in the UV maximum of 3 from 286 nm to 321-325 nm. The reaction of 3 with 2-mercaptoethanol gave cis-6-[2[(2-hydroxyethyl)-thio]vinyl]uracil as the predominant product. Compounds 2 and 3 inhibited the growth of leukemia L1210, B-16 melanoma, and lewis lung carcinoma cells at concentrations ranging from 1 x 10(-6) to 2 x 10(-5) M. As determined with L1210 cells, the inhibition of growth caused by 2 and 3 was not prevented by the natural pyrimidines, indicating that the agents do not act as antimetabolites.

Alkylating Agents↗

[Physical training in high altitude].

Hemodynamic parameters and myocardial extraction of lactate and free fatty acids (FFA) have been studied at rest and during exercise (bicycle) in 9 mountain climbers who spent 4 weeks in the Himalayas at an altitude of 5500-7000 m. All investigations were performed before and immediately after the stay at high altitude. The combined effect of physical training and hypoxemia of high altitude did not alter the hemodynamic parameters, calculated VO2 max, production of lactate or decrease of FFA during the exercise test, but myocardial extraction of lactate and FFA changed. After returning from the expedition myocardial extraction (at rest and during exercise) of lactate increased and that of FFA decreased. The reasons for these alterations and their goals and implications are discussed.

Adult↗

Comparative results of postmastectomy rehabilitation in a specialized and a community hospital.

This article describes results of postmastectomy rehabilitation program as operating at Mt. Sinai Hospital of Cleveland, a general community facility. Common physical and emotional problems following mastectomy are documented, as well as barriers to effective rehabilitation--particularly the fact that such programs are usually associated with specialized oncology settings and not seen as feasible in the community hospital. An analysis of outcomes of a program operated at both Mt. Sinai and Memorial Sloan-Kettering Cancer Center demonstrates that comparable and positive patient outcomes can be achieved in terms of range of motion, resumption of prior activities, and emotional stress. Recommendations are made regarding ways to overcome common problems in implementing such programs in an inexpensive and effective manner.

Activities of Daily Living↗