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Biomedical subjects

L Sachs

Publications and source records attributed to L Sachs.

At least 217 records · Page 12Linked to original sources
PubMed1978

Control of normal differentiation of myeloid leukemic cells. XIII. Inducibility for some stages of differentiation by dimethylsulfoxide and its disassociation from inducibility by MGI.

There are clones of myeloid leukemic cells that can be induced to differentiate by the normal differentiation-inducing protein MGI to form Fc and C3 rosettes, mature macrophages and granulocytes. One of these clones (MGI+DMSO+) was also inducible by dimethylsulfoxide (DMSO) for C3 but not Fc rosettes, and for mature macrophages but not for mature granulocytes. Other clones (MGI+DMSO-) were inducible by MGI but not DMSO and a third type of clone (MGI-DMSO-) was not inducible by either compound. Clones that differed in their inducibility by DMSO showed a similar inhibition of cell multiplication by DMSO. The results indicate, that some stages of differentiation can be induced by DMSO in an appropriate clone of myeloid leukemic cells and that there are different cellular sites for induction by DMSO and MGI.

Cell Differentiation↗
PubMed1978

Nuclear control of neurite induction in neuroblastoma cells.

Induction of neurite formation in neuroblastoma cells by dibutyryl cyclic 3':5'-AMP (db-cAMP) or prostaglandin EI (PGE1) was enhanced after enucleation. Cells selected for resistance to db-cAMP were induced to form neurites by db-cAMP or PGE1 only after, but not before enucleation. Inhibition of protein synthesis inhibited neurite induction in nucleated, but not in enucleated cells, and enucleated cells were less sensitive to inhibition of neurite formation by concanavalin A (ConA). Colchicine, vinblastine and cytochalasin B (CB), compounds that interfere with the assembly of microtubules and microfilaments, inhibited induction in both types of cells. It is suggested that enucleation removes a nuclear inhibitor of neurite induction by db-cAMP and PGE1, and that neurite induction in nucleated cells requires that cAMP activates the assembly of microtubules and microfilaments and inactivates the nuclear inhibitor.

Alprostadil↗
PubMed1978

Co-regulation of type C RNA virus production and cell differentiation in myeloid leukemic cells.

Mouse myeloid leukemic cells which differ in their competence to be induced to differentiate by the normal macrophage- and granulocyte-inducing protein MGI have been used to study the relationship between type C RNA virus production and myeloid cell differentiation. Clones which can be induced by MGI to form Fc and C3 rosettes, to synthesize and secrete lysozyme and to differentiate to mature macrophages and granulocytes (MGI+D+) were induced by MGI to produce higher amounts of type C virus. Clones (MGI+D-) that were less inducible by MGI for Fc and C3 rosettes and lysozyme and were not induced to from mature cells were also less inducible higher virus production. In both types of clones, the increased virus production induced by MGI preceded the induction of rosettes and lysozyme. Clones that were not induced by MGI for rosettes or lysozyme (MGI-D-) showed little or no enhancement of virus production. MGI did not affect virus production in erythroleukemic cells, and erythropoietin did not affect virus production in the myeloid leukemic cells. Dexamethasone, lipopolysaccharide, dimethylsulfoxide and low concentrations of actinomycin D can induce some differentiation-associated properties in some of the clones. With these compounds, there was also a direct relationship between the enhancement of virus production and induction of differentiation-associated properties. Virus released from the three types of clones before or after treatment with MGI or dexamethasone was identified as N-tropic. The enhancement of virus production, as measured by reverse transcriptase activity, was accompanied by an increase in the amount of the viral protein p30, and interferon, which idd not inhibit the induction of differentiation in the myeloid leukemic cells, also did not prevent the increase in the amount of p30. After the early enhancement of virus production associated with the induction of differentiation, a shut-off of virus production occurred in the mature cells induced by MGI in MGI+D+ clones, whereas clones that did not differentiate to mature cells continued to produce virus. The results indicate that enhancement of virus production appears to be an early step in the induction of differentiation. Once induction has occurred, the lack of virus production in the mature cells suggest that a subsequent shut-off of virus production may be required for the completion of differentiation to mature cells. This relationship between cell differentiation and virus production suggests that type C virus has a regulatory role in myeloid cell differentiation.

Animals↗
PubMed1978

Indirect induction of differentiation in myeloid leukemic cells by lipid A.

Normal myeloid and MGI(+)D(+) clones of myeloid leukemic cells can be induced for Fc and complement component 3 rosettes, lysozme, and mature macrophages and granulocytes by a protein with macrophage- and granulocyte-inducing (MGI) activity, whereas MGI(+)D(-) clones can be induced by this protein for rosettes and lysozme but not mature cells. Lipopolysaccharides (LPS) from different bacteria induced the appearance of rosettes, lysozyme, and macrophages in some MGI(+)D(+) clones but did not induce any of these changes in MGI(+)D(-) clones. Lipid A gave the same results as LPS. Incubation of MGI(+)D(+) cells with LPS also induced an MGI activity detectable in the culture medium. This activity behaved like MGI in inducing (i) rosettes, lysozyme, and mature cells in MGI(+)D(+) leukemic cells including a clone resistant to LPS, (ii) rosettes and lysozyme in MGI(+)D(-) leukemic cells, and (iii) differentiation of normal myeloid cells to mature macrophages and granulocytes. This activity was induced in MGI(+)D(+) cells by LPS before the induction of rosettes or lysozyme. The results indicate that the lipid A portion of LPS indirectly induces differentiation of MGI(+)D(+) myeloid leukemic cells by inducing MGI protein. It is suggested that induction of specific regulatory proteins may be a more general mechanism for the induction of differentiation by surface-acting compounds.

Animals↗
PubMed1978

Differential desensitization of functional adrenergic receptors in normal and malignant myeloid cells: relationship to receptor-mediated hormone cytotoxicity.

Malignant myeloid leukemic cells and normal macrophages and granulocytes have functional beta-adrenergic receptors, which have been quantitated by radioreceptor binding with the beta-adrenergic antagonist [(3)H]dihydroalprenolol and by induction of cyclic AMP by adrenergic hormones. Both the normal and leukemic cells have beta(2)-adrenergic receptors, and the [(3)H]dihydroalprenolol binding was saturable, reversible, and stereospecific. The leukemic cells consisted of clones that could be induced to differentiate (MGI(+)D(+)) and clones that could not be induced to differentiate to mature macrophages and granulocytes by the protein inducer MGI. The different types of leukemic clones all had 1100-2300 receptor sites per cell, whereas normal macrophages had 7000 receptors per cell. The differentiation of MGI(+)D(+) leukemic cells was associated with an increase in receptors to a number similar to that found with normal macrophages. MGI(+)D(+) leukemic cells and normal macrophages were able to densensitize to the beta-adrenergic agonist (-)isoproterenol, shown by termination of cyclic AMP induction within 10-15 min and the lack of a second induction. The leukemic cells that could not be induced to differentiate lacked this capacity for desensitization, possibly due to an alteration in the uncoupling system between the receptor and adenylate cyclase. The lack of desensitization in these leukemic cells was associated with a higher sensitivity to the receptor-mediated cytotoxic effects of adrenergic hormones. It is suggested that cells, like some leukemic cells, that are unable to desensitize to adrenergic and possibly other hormones may be appropriate targets for differential destruction by hormones under conditions that do not affect normally desensitizing cells.

Adenylyl Cyclases↗
PubMed1978

In vivo induction of normal differentiation in myeloid leukemia cells.

MGI(+)D(+), MGI(+)D(-), and MGI(-)D(-) mouse myeloid leukemic cells, which genetically differ in their competence to be induced to undergo normal cell differentiation in vitro by the normal macrophage- and granulocyte-inducing protein MGI, were analyzed for their ability to undergo cell differentiation in diffusion chambers in vivo. As after induction by MGI in vitro, MGI(+)D(+) clones were induced for Fc and C3 rosettes, lysozyme, and mature macrophages and granulocytes in normal syngeneic or allogeneic mice. MGI(+)D(-) clones were also induced in these mice for all these properties, although in vitro they were not induced by MGI for mature cells. The MGI(-)D(-) clones were induced in vivo for C3 and Fc rosettes, lysozyme, and intermediate stages but not for mature cells, whereas none of these properties were induced in these clones by MGI in vitro. Thus, certain types of myeloid leukemic cells differentiate better in vivo, possibly due to the presence of higher effective concentrations of MGI and/or other inducing factors, and MGI(+)D(+) and MGI(+)D(-) cells can completely differentiate in vivo to mature cells. In vivo differentiation was inhibited in mice treated with cyclophosphamide. It was also inhibited in various strains of nude mice, except for one MGI(+)D(+) clone, where it was inhibited in C57BL/6 but not in ICR nude mice. This MGI(+)D(+) clone was also the only clone that was induced to differentiate normally in vitro by a 23,000 molecular weight form of purified MGI. The results suggest that different clones respond to different molecular forms of MGI, which may be present in different proportions in some animals, that in vivo differentiation by MGI possibly with other factors may be regulated by cells involved in the immune response, and that this differentiation can be genetically controlled. Differentiation in vivo was enhanced by injection of conditioned medium containing MGI and by inoculation of MGI-producing cells, including normal granulocytes. This indicates that the induction of normal differentiation of myeloid leukemic cells in vivo can be enhanced by these treatments.

Animals↗
PubMed1978

Control of cloning of normal human T lymphocytes by transferrin, albumin and different lectins.

Normal human T-lymphocytes can be induced to form colonies with a high cloning efficiency by seeding the cells directly in agar with normal human plasma and the lectins concanavalin A, phytohaemagglutinin, or pokeweed mitogen. The requirement for human plasma can be substituted, to different degrees with different lectins, by adding transferrin and albumin to foetal calf serum. This provides a useful system for identifying specific deficiencies in the requirements for normal T-lymphocyte colony formation.

Cell Division↗
PubMed1977

[Graphical methods in data analysis (author's transl)].

Data analysis is concerned with attentive description and communication of the information contents of a body of data. Background information, conceptual insight and especially graphical methods play a key role in data analysis for developing a feeling for the data both by formal procedures to be applied in the light of specified models and even more by informal inference or methods that are suggestive and conctructive. This paper reviews graphical methods useful for description, screening, analysis, cross-examining, selection, reduction, presentation and summary of data: for uncovering distributional peculiarities and understanding the structure underlying experimental and survey data. Moreover scatter plots, probability plots and residual plots provide insight into the possible inappropriateness of certain assumptions of the statistical model. Some techniques are illustrated by examples: four-dimensional data may be reprented as scatter plot on ordinary graph paper by using a combination of 2 different sets of symbols for at most 7 different levels of the third variable (formula: see text) and of the fourth variable (formula: see text). Comments on the use of tables and graphical methods, a small overview of the latter and of the scope of applications endeavour to pave the way such that structures may be better understandable and unanticipated characteristics may be spotted.

Factor Analysis, Statistical↗
PubMed1977

[Statistical methods in medicine: in instruction, consultancy and research (author's transl)].

This survey covers the use of statistical methods in three areas of medicine: (1) the obligatory instruction of students in statistics, (2) the statistical consulting of clinicians and their candidates for a doctor's degree and (3) the modification and creation of statistical methods by the statisticians in the departments of medical statistics and documentation. Moreover some factors are discussed that reduce the effectiveness of statistical consulting, may it be service, advisory work or collaboration. Other sections of this paper cover the calamity of utilization and evaluation of old clinical records, the avoidance of fallacies and of errors committed by the inappropriate and incorrect application of statistical methods in medicine. Supplementary questions are given as a "first help" in tackling problems in medicine.

Education, Medical, Graduate↗
PubMed1977

Transformation of normal hamster cells by benzo(a)pyrene diol-epoxide.

The frequency of cell transformation was determined after treatment of normal hamster embryo cells with benzo(a)pyrene (BP) and six of its metabolites. These metabolites included the trans 4,5-, 7,8- and 9,10-dihydrodiols; the 4,5-epoxide; and two stereoisomers of the non-K-region diol epoxides r-7, t-8-dihydroxy t-9, 10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 1) and r-7, t-8, dihydroxy c-9, 10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 11). The trans 7,8-dihydrodiol was more active than the other two dihydrodiols tested and was also more active than the parent hydrocrabon BP. Of the three epoxides tested, the diol-epoxide 1 was more active than the 4,5-epoxide and diol-epoxide 11. The results suggest that diol-epoxide 1 is a major cell-transforming metabolite of BP.

Animals↗
PubMed1977

Surface membrane changes in lymphocytes from patients with infectious mononucleosis.

Peripheral blood lymphocytes from 20 patients with acute infectious mononucleeosis (IM) were studied for cell aggregation and for cap formation by concanavalin A (Con A). The lymphocytes from these patients showed 5.2+/-1.5% cells with a Con-A-induced cap and a high degree of cell aggregation without Con A, compared to 27.7+/-3.2% caps and a low degree of cell aggregation with normal lymphocytes. The lymphocytes from IM patients were fractionated to enrich for T and B cells. There was a low frequency of cap formation in both T and B cells, but the high degree of celll aggregation without Con A only occurred with B cells. Studies with four patients in clinical remission from acute IM have shown that the frequency of Con-A-induced cap formation only returned to normal more than 3 months after the beginning of clinical remission and that even at 6 months the cells still showed a high degree of cell aggregation. The results indicate that a high degree of B-cell aggregation and a low percentage of B and T cells with a Con-A-induced cap were associated with acute IM and that the changes associated with a high degree of B-cell aggregation were by themselves not sufficient to cause the disease.

Acute Disease↗