PubMed Health⌕ Search

Biomedical subjects

M Kamber

Publications and source records attributed to M Kamber.

15 recordsLinked to original sources
PubMed1995

Enhancement of HL-60 differentiation by a new class of retinoids with selective activity on retinoid X receptor.

Cellular responsiveness to retinoic acid and its metabolites is conferred through two distinct families of receptors: the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Herein, we report on the identification and characterization of several conformationally restricted retinoids, which selectively bind and activate RX receptors. Under the influence of retinoids, HL-60 myelocytic leukemia cells differentiate into granulocytes. This effect is mediated by RAR alpha, as has been demonstrated through the use of a selective RAR alpha antagonist (Apfel, C., Bauer, F., Crettaz, M., Forni, L., Kamber, M., Kaufmann, F., LeMotte, P., Pirson, W., and Klaus, M. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 7129-7133). Here, we show that conformationally restricted RXR-specific retinoids, at doses that are per se inactive, are able to potentiate by up to one order of magnitude the pro-differentiating effects of all-trans retinoic acid and an RAR alpha-selective synthetic retinoid. We also present evidence that these RXR-selective ligands are able to bind to a DNA RXR.RAR heterodimer complex. This finding demonstrates that agonists for RARs and RXRs can synergistically promote HL-60 differentiation, which could be mediated through a heterodimer of these receptors.

Binding, Competitive↗
PubMed1995

[Doping].

The use of performance-enhancing drugs and methods has been known for centuries. Man always tried to expand his given natural limits. In sport, these practices are called 'doping' and are forbidden by the rules. Today, doping is the advertent or inadvertent use of substances of forbidden classes or of forbidden methods defined by the actual doping list. This doping list is a so-called 'open' list that does not mention all substances within a forbidden class, but only some examples. This imposes high demands on physicians treating athletes. The Commission against Doping of the Swiss Sports Federation helps in case of questions about medical treatments. The Swiss Federation of Sports Medicine confirmed lately its fight against doping with a formal position paper.

Adolescent↗
PubMed1992

A retinoic acid receptor alpha antagonist selectively counteracts retinoic acid effects.

Retinoic acid (RA) exerts its pleiotropic effects on cell growth and differentiation through the activation of a family of transcription factors-the RA receptors (RARs). Three subtypes of these receptors exist, RAR alpha, RAR beta, and RAR gamma. The receptors are differentially expressed in different cell types and stages of development, suggesting that they may regulate different sets of genes. We have identified a synthetic retinoid with the characteristics of a selective RAR alpha antagonist. This antagonist counteracts RA effects on HL-60 cell differentiation and on B-lymphocyte polyclonal activation. Beyond its potential practical relevance, this and other specific antagonists will be useful to dissect the RAR system and to assign to one given receptor each of the many RA-regulated functions.

Animals↗
PubMed1992

Human monoclonal antibodies against Plasmodium falciparum: production, stabilization and characterization.

Nine human monoclonal antibodies (MoAbs) recognizing 7 different antigenic structures of blood-stages of the human malarial parasite P. falciparum (Pf) were produced by Epstein-Barr virus transformed B-cell lines (EBV-TCL) with or without fusion to the lymphoblastoid cell line KR4. The peripheral blood B-lymphocytes were obtained from 8 Gambian donors immune to Pf malaria. Two of the EBV-TCL could be expanded and maintained for more than 6 months but neither one could be cloned. Six additional EBV-TCL were stabilized after fusion with the KR4 lymphoblastoid cell line. All resulting hybridomas permitted easy cloning. Some of the MoAbs produced distinct fluorescent staining patterns of asexual Pf blood-stage parasites when using high-resolution digitized video-intensified fluorescence microscopy. Antigens on 195 kD and 155 kD proteins were recognized by 3 and 1 MoAb, respectively, using Western blotting and immunoprecipitation techniques.

Animals↗
PubMed1992

[Lactate measurements in sports medicine: comparison of analytic methods].

The measurement of lactate is a major aid for controlling the capacity of an athlete and for establishing individual training schedules. The results are affected by different factors like the site of blood sampling or the distribution of lactate in the blood. The aim of the study was to investigate under constant conditions the results of four different commercially available methods for measuring lactate in blood. All methods were first tested with pure standards of lactate and with different reference sera. Both the accuracy and the reproducibility of the results were good. One method (Lange) showed good accuracy at room temperature but the values were too low at higher temperatures. The enzymatic method was then chosen as reference method for investigations with blood samples. The first method (ESAT) showed excellent correspondence, the results of the second (Lange) were 5-10% too low, and the third method (YSI) showed results too low and were also susceptible to trouble.

Blood Chemical Analysis↗
PubMed1991

GM-1, a clone of the monoblastic phagocyte U937 that expresses a large respiratory burst capacity upon activation with interferon-gamma.

The human cell line U937 was cloned and screened for the responsiveness to interferon-gamma (INF-gamma). The selected subclone, named GM-1, expressed a high density of IFN-gamma receptors and showed HLA typing similar to that of the parental line but was devoid of the Y chromosome. GM-1 cells display a promyeloid phenotype as revealed by flow cytometry using a panel of murine antibodies. Following treatment with IFN-gamma GM-1 cells differentiated to a more mature monocyte stage and acquired the capacity to mount a respiratory burst. After treatment with differentiation promotors, such as phorbol 12-myristate 13-acetate (PMA), dimethyl sulfoxide (DMSO), and retinoic acid, GM-1 showed a more limited respiratory burst capacity. Superoxide release in IFN-gamma-activated cells was stimulated with f-Met-Leu-Phe, C5a, or PMA. The development of the respiratory burst capacity was accompanied with the expression of cytochrome b558, a component of the phagocyte NADPH-oxidase. GM-1 cells are useful for the study of the effects of IFN-gamma on the respiratory burst. They are more sensitive and yield a more homogenous response to IFN-gamma than U937 cells. The phenotype of GM-1 cells was stable for more than 5 years.

Antigens, CD↗
PubMed1990

[The fight against doping: international and national efforts as exemplified by the Convention of the Council of Europe and the doping regulations of the Swiss National Association for Sports].

The international and national efforts to flight doping in sports are shown by the examples of the Anti-Doping Convention of the Council of Europe and the regulations of the Swiss Association of Sports. Major efforts are made in the fields of education and information, search for and application of optimal methods for training and care as well as dope-controls at and out of competitions. The harmonization of the anti-doping regulations and the disciplinary procedures that have to follow the principles of natural justice are considered to be important. The Swiss regulations allow, at variance with international customs, to treat injured athletes therapeutically with doping-substances.

Anabolic Agents↗
PubMed1990

[Analysis of doping: possibilities and limitations].

The role of modern instrumental analysis in today doping control procedures is described. With reference to the analytical methods, to the requirements of the International Olympic Committee for laboratory accreditation and to the regulations for substantiating a positive result, we show how a laboratory for doping control is functioning. The limits of today analyses are shown, making it obvious that the analytical results from an accredited laboratory are not the weak point in doping control.

Algorithms↗
PubMed1988

The role of lipids in Plasmodium falciparum invasion of erythrocytes: a coordinated biochemical and microscopic analysis.

The role of lipids in Plasmodium falciparum invasion of erythrocytes was investigated by biochemical and fluorescent microscopic analysis. Metabolic incorporation of radioactive oleate or palmitate and fractionation of radiolabeled phospholipids by thin-layer chromatography revealed no difference in the major phospholipid classes of schizonts and early ring forms after merozoite invasion. Fluorescent anthroyloxy derivatives of oleate and palmitate were also metabolically incorporated into parasite phospholipids. By microscopic analysis, the fluorescent phospholipids were seen localized in the plasma membrane and, within the merozoite, concentrated near the apical end. During invasion fluorescent phospholipid appeared to be injected from the apical end of the merozoite into the host membrane, both within and outside the parasite-host membrane junctions. After invasion fluorescent lipid was only found in the parasite plasma membrane and/or parasitophorous vacuole membrane. Parallel experiments with a fluorescent cholesterol derivative, incorporated into parasite membranes by exchange, revealed neither heterogeneous distribution of label within the parasite nor evidence for cholesterol transfer from merozoite to host cell membrane. Results suggest that during invasion no major covalent alteration of parasite lipids, such as lysophospholipid formation, occurs. However, invasion and formation of the parasitophorous vacuolar membrane apparently involves insertion of parasite phospholipids into the host membrane.

Animals↗
PubMed1987

Functional maturation of murine B lymphocyte precursors. II. Analysis of cells required from the bone marrow microenvironment.

The development of mature B cells in cultures of early B cell precursors depends on the presence of a confluent adherent bone marrow (aBM) cell layer. Adherent and sIgM+ cell-depleted bone marrow (BM) from untreated or 5-fluorouracil-pretreated donors or day 12 fetal liver cells were used as precursor cell populations. When adherent cells from thymus or highly enriched BM-derived macrophages were co-cultured with precursor cells, mature B cells were not developed. Similarly, aBM cell layers generated in the presence of hydrocortisone and horse serum were unable to support aBM cell-dependent precursor differentiation, even though cortisone was removed before the addition of precursor cells. In contrast, this type of microenvironment promoted the differentiation of precursor of myeloid cell lineages. Repeated treatment of established aBM cell populations with a monoclonal anti-macrophage antibody (31.3, known to recognize a surface marker on a subset of BM macrophages) and complement abolished the capacity of otherwise functional aBM cells to sustain the development of B cell precursors. Macrophage-depleted aBM cells regained their function after supplementation with highly enriched BM-derived macrophages grown in vitro. Limiting dilution analysis of aBM cells in microcultures containing saturating numbers of early B cell progenitors also suggests the participation of more than one cell type in the BM cell population. In conclusion, differentiation of early B cell progenitors requires macrophages in addition to at least one additional cell type contained in the aBM cell population.

Animals↗
PubMed1987

Recombinant interferons or interleukin-2 increase cytotoxicity by human monocytes and NK cells.

Human peripheral blood monocytes and NK cell enriched lymphocytes were purified by counterflow centrifugal elutriation. The cell populations were characterized by surface marker analysis using monoclonal antibodies. A variety of molecules were found to be capable of activating monocytes and NK cells to enhanced tumoricidal activity. Tumoricidal activity was evaluated using a colorimetric microassay. Numbers of tumor cell targets surviving exposure to monocytes or NK cells were calculated by computer analysis of colorimetric data derived by target cell-dependent dye reduction. The results indicated that monocyte effector cells were cytotoxic to the NK sensitive K562 cell line and to the monocyte sensitive TU5 line. Depletion of NK contaminants from the monocyte population by complement mediated cytolysis did not affect the capacity of the monocytes to kill either target. Monocyte mediated cytotoxicity was enhanced by treatment of the monocytes with recombinant IFN-alpha, IFN-beta, or IFN-tau; each in a dose-dependent manner. Simultaneous treatment of monocytes with IFN-alpha and IFN-tau resulted in additive but not synergistic effects. NK cell cytotoxicity was enhanced by treatment with IL-2 or IFN-tau. Enhancement of monocyte and NK cell cytotoxicity by IFN or IL-2 was dependent upon the time in culture of the effector cells, the duration of the effector phase, and the effector to target cell ratio. IFN or IL-2 treatment alone did not reduce target cell viability. The results suggest that monocytes as well as NK cells are capable of providing a natural defence against neoplasia, that monocytes can kill NK targets and NK cells can kill monocyte targets, and that these cytotoxic activities are enhanced by IFN or IL-2.

Cell Line↗
PubMed1986

Phorbol myristate acetate-induced proliferation of an IL-2-dependent T-cell line: action of PMA is independent of IL-2 and cannot be mimicked by diacylglycerols.

Phorbol myristate acetate (PMA) at concentrations of 2 X 10(-10) to 2 X 10(-7) M was able to sustain proliferation of the interleukin 2 (IL-2)-dependent murine T-cell line CTLL-K. This line, which died within 24 hr without exogenously added IL-2, survived for at least 96 hr and completed two to three cycles of replication in the presence of an optimal dose of PMA. PMA did not increase proliferation induced by saturating amounts of IL-2, but it mimicked IL-2 activity when no IL-2 or only suboptimal doses of IL-2 were present. This effect was completely independent of any residual IL-2 activity and was not mediated by the endogenous production of IL-2. The finding that stimulation of CTLL-K cells with 1-oleoyl-2-acetyl-glycerol or 1,2-dioctanoyl-glycerol rather than with PMA was not sufficient to induce any proliferation suggests that diacylglycerols and phorbol esters have qualitatively different effects on protein kinase C activity. Falsely positive results could occur when IL-2-dependent T-cell lines were used as indicator cells for IL-2, since evidence is presented that PMA-responsive cells could emerge spontaneously from T-cell clones that originally were not responsive or only weakly influenced by PMA.

Animals↗
PubMedDate not supplied

3D simulation of PET brain images using segmented MRI data and positron tomograph characteristics.

A 3D simulation procedure has been developed to generate simulated PET brain images from MRI data. MRI slices were segmented into gray matter, white matter, CSF structures, and assigned with radionuclide distributions. Projections through these regions were generated according to physical characteristics of a positron tomograph, including 3D sampling and resolution, attenuation, scatter, randoms, and counting statistics. The projection data were then reconstructed by filtered backprojection. The procedure was validated with a cold spot phantom. Simulated PET images for cerebral blood flow or metabolism are presented, along with a brief discussion of some applications and limitations.

Brain↗
PubMedDate not supplied

3D simulations of radiotracer uptake in deep nuclei of human brain.

The accuracy of Positron Emission Tomography (PET) for measuring in vivo concentrations of radiolabelled pharmaceuticals is affected by the limited tomograph resolution. Using computer simulations, we developed a model reproducing the distribution of the tracer [18F]fluoroDOPA which is specifically taken up in the normal human striatum. Validation of the model was performed by comparing the simulated images with real PET scans of the same brain. The simulation was used to examine the effect of axial displacement of the brain relative to the PET imaging planes, and that of image contrast on signal recovery (partial volume effects).

Brain↗