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M Schreier

Publications and source records attributed to M Schreier.

9 recordsLinked to original sources
PubMed1999

Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis.

By virtue of its potential effects on rates of energy expenditure, uncoupling protein 3 (UCP3) is an obesity candidate gene. We identified nine sequence variants in UCP3, including Val9Met, Val102Ile, Arg282Cys, and a splice site mutation in the intron between exons 6 and 7. The splice mutation results in an inability to synthesize mRNA for the long isoform (UCP3L) of UCP3. Linkage (sib pair), association, and transmission disequilibrium testing studies on 942 African-Americans did not suggest a significant effect of UCP3 on body composition in this group. In vastus lateralis skeletal muscle of individuals homozygous for the splice mutation, no UCP3L mRNA was detectable; the short isoform (UCP3S) was present in an increased amount. In this muscle, we detected no alterations of in vitro mitochondrial coupling activity, mitochondrial respiratory enzyme activity, or systemic oxygen consumption or respiratory quotient at rest or during exercise. These genetic and physiologic data suggest the following possibilities: UCP3S has uncoupling capabilities equivalent to UCP3L; other UCPs may compensate for a deficiency of bioactive UCP3L; UCP3L does not function primarily as a mitochondrial uncoupling protein.

Alternative Splicing↗
PubMed1998

Comparison of the phagocytosis of two types of cyclosporin (SDZ OXL 400 and SDZ IMM 125) by alveolar macrophages from hamsters.

The aim of this study was to compare two types of cyclosporin (Cs) particles, SDZ OXL 400 and SDZ IMM 125, the latter being more hydrophilic, to understand their uptake by airway macrophages. Alveolar macrophages (AM), harvested by bronchoalveolar lavage (BAL) of hamster lungs, were cultured with two different doses (0.1 mg and 0.5 mg) for 1 h, 6 h, and 24 h. Control incubations without Cs particles or with latex particles were carried out simultaneously. Cell viability, cell activation (i.e., respiratory burst, interleukin-6 (IL-6) synthesis) and mean volume of particles phagocytosed per macrophage were measured. Both types of Cs particles did not modify the AM viability, and failed to induce IL-6 synthesis during phagocytosis but slightly decreased the cell oxidative respiratory burst. The comparison between SDZ OXL 400 and SDZ IMM 125 showed that for the lower dose the mean volume of both Cs types phagocytosed was similar at 1 h and 6 h. At 24 h an increase of the mean volume phagocytosed was seen for SDZ IMM 125 but not for SDZ OXL 400. For the higher dose the mean volume of SDZ IMM 125 phagocytosed was higher than SDZ OXL 400 at 1 h and 6 h and comparable for both types at 24 h. SDZ IMM 125 particles were phagocytosed more rapidly than SDZ OXL 400. The mean volume of phagocytosed latex particles increased with time and dose and was higher than for both Cs particle types. In conclusion, AM were seen to phagocytose particles of different physical properties (i.e., form, size, and shape), chemical properties (i.e., inert or peptidic) and degrees of hydrophilicity in a different manner.

Animals↗
PubMed1996

Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape.

Malignant melanoma accounts for most of the increasing mortality from skin cancer. Melanoma cells were found to express Fas (also called Apo-1 or CD95) ligand (FasL). In metastatic lesions, Fas-expressing T cell infiltrates were proximal to FasL+ tumor cells. In vitro, apoptosis of Fas-sensitive target cells occurred upon incubation with melanoma tumor cells; and in vivo, injection of FasL+ mouse melanoma cells in mice led to rapid tumor formation. In contrast, tumorigenesis was delayed in Fas-deficient lpr mutant mice in which immune effector cells cannot be killed by FasL. Thus, FasL may contribute to the immune privilege of tumors.

Animals↗
PubMed1994

[Cyclosporin in autoimmune diseases].

At a symposium held in Zurich in November 1993, a series of presentations covered the optimal use of cyclosporin A (CsA) in autoimmune diseases. Besides its immunosuppressive effects in organ transplantation, CsA appears to be active in a variety of autoimmune disorders. Its most pronounced and beneficial clinical effects are seen in patients with severe rheumatoid arthritis. New clinical studies include the nephrotic syndrome in children and patients with systemic lupus erythematodes. The main concern remains CsA induced nephrotoxicity. For the treatment of autoimmune disorders CsA can be used at lower doses (< or = 5 mg/kg per day) than in transplantation medicine. Thus, monitoring of CsA blood concentrations is not usually necessary. The galenics of CsA has been optimized recently, an achievement which will further improve the clinical use of CsA. Due to increased knowledge of intracellular CsA binding proteins and of effects of CsA on T-lymphocytes and cytokine production, it can be expected that novel immunosuppressive compounds will be developed.

Adult↗
PubMed1993

Cyclosporins. Structure-activity relationships.

Cyclosporin A (Sandimmun) achieves immunosuppressive activity by complex formation with cyclophilin and subsequent binding of the binary complex to and inhibiting protein phosphatase 2B (calcineurin). Complexes of nonimmunosuppressive cyclophilin binding cyclosporin analogues do not inhibit protein phosphatase 2B, suggesting a crucial role for this enzyme in T cell activation. Binding of cyclosporin A to cyclophilins A, B, and C, respectively, results in complexes of significantly different inhibitory potency. The cyclosporin molecule thus has two functional domains, one mediating cyclophilin binding and a second one endowing affinity of the complex to calcineurin, thereby inhibiting its enzyme activity. Structure-activity studies and x-ray crystallography of cyclosporin-cyclophilin complexes indicate a crucial role of leucine side chains in positions 4 and 6 of the cyclosporin macrocycle for the calcineurin interaction.

Amino Acid Sequence↗
PubMed1978

Induction of haemolytic plaque-forming cells with sheep lymphoid cells in vitro.

The in vitro induction of specific primary and secondary immune responses in sheep lymph node cell suspensions is described and suitable culture conditions determined. The induction of primary immune responses required supplementation of the culture medium with antigen-absorbed homologous serum or lymph, whereas the requirements for the induction of a secondary response were less stringent. The addition of 2-mercaptoethanol to the medium was required. The amounts of heterologous erythrocytes used for immunization were critical and optimal responses were obtained when 50 microleters of a 1% suspension were added to 1 ml cultures. Lymphocyte densities of about 5 X 10(6)/ml were found optimal in primary immune responses in vitro. Less than 2 X 10(6) cells/ml rarely gave rise to plaque-forming cell (PFC) generation, whereas densities of 10 x 10(6) and above reduced the number of PFC obtained per number of cultured cells. Lymphocytes obtained from the efferent lymph draining lymph nodes previously immunized with heterologous erythrocytes were found to generate PFC in vitro when specific antigen was added to the cultures, but attempts to generate PFC in vitro with cells from efferent lymph draining non-immunized nodes failed.

Animals↗