Francine Lambert

Myosin molecular motor dysfunction in dystrophic mouse diaphragm.

Cross-bridge properties and myosin heavy chain (MHC) composition were investigated in isolated diaphragm from 6-mo-old control ( n = 12) and mdx( n = 12) mice. Compared with control, peak tetanic tension fell by 50% in mdx mice ( P < 0.001). The total number of cross bridges per square millimeter (×109), the elementary force per cross bridge, and the peak mechanical efficiency were lower in mdx than in control mice (each P < 0.001). The duration of the cycle and the rate constant for cross-bridge detachment were significantly lower in mdx than in control mice. In the overall population, there was a linear relationship between peak tetanic tension and either total number of cross bridges per square millimeter or elementary force per cross bridge ( r = 0.996 and r = 0.667, respectively, each P < 0.001). The mdx mice presented a higher proportion of type IIA MHC ( P < 0.001) than control mice and a reduction in type IIX MHC ( P < 0.001) and slow myosin isoforms ( P < 0.01) compared with control mice. We concluded that, in mdx mice, impaired diaphragm strength was associated with qualitative and quantitative changes in myosin molecular motors. It is proposed that reduced force generated per cross bridge contributed to diaphragm weakness in mdx mice.Cross-bridge properties and myosin heavy chain (MHC) composition were investigated in isolated diaphragm from 6-mo-old control (n = 12) and mdx (n = 12) mice. Compared with control, peak tetanic tension fell by 50% in mdx mice (P < 0.001). The total number of cross bridges per square millimeter (x10(9)), the elementary force per cross bridge, and the peak mechanical efficiency were lower in mdx than in control mice (each P < 0.001). The duration of the cycle and the rate constant for cross-bridge detachment were significantly lower in mdx than in control mice. In the overall population, there was a linear relationship between peak tetanic tension and either total number of cross bridges per square millimeter or elementary force per cross bridge (r = 0.996 and r = 0.667, respectively, each P < 0.001). The mdx mice presented a higher proportion of type IIA MHC (P < 0.001) than control mice and a reduction in type IIX MHC (P < 0.001) and slow myosin isoforms (P < 0.01) compared with control mice. We concluded that, in mdx mice, impaired diaphragm strength was associated with qualitative and quantitative changes in myosin molecular motors. It is proposed that reduced force generated per cross bridge contributed to diaphragm weakness in mdx mice.

Mixed lymphocyte reaction in mice genetically selected for high (Hi/PHA) or low (Lo/PHA) responsiveness to phytohemagglutinin☆

Abstract Lymph node cells from Hi/PHA and Lo/PHA mice were evaluated for proliferative response after stimulation by allogeneic lymphocytes (MLR) originating from four inbred strains of different H-2 haplotype (C57B1/6, DBA/2, CBA, A). Reactivity to MLR and PHA were compared in these two lines and in the four inbred strains. The high and low responder status of Hi/PHA and Lo/PHA, as determined by T mitogens lymphocyte responsiveness, was also observed when one measured T responsiveness after MLR. Values obtained with the four inbred strains are included in the range of those measured in Hi/PHA and Lo/PHA cells when stimulated by PHA as well as by allogeneic cells. In contrast, when used as stimulator cells, Hi/PHA or Lo/PHA lymphocytes induce an equivalent proliferative response versus every responder inbred strain studied. These experiments support the hypothesis of a common genetic control of proliferative response following PHA or MLR stimulation. The genes implicated would be different from those coding for I region associated antigens.

Relations Between Myocardial Contractility, Myosin Phenotype, and Plasma Angiotensin-converting Enzyme Activity in the Cardiomyopathic Hamster

Summary Angiotensin-converling enzyme (ACE) inhibitors have been shown to preserve myocardial contractility in the cardiomyopathic Syrian hamster (CSH). To determine if this was related to changes in myosin heavy-chain (MHC) phenotype. myosin isoform patterns and mechanical properties were studied in the same left ventricular papillary muscle from CSH of the Bio 53.58-dilated strain. From age 1 to 6 months. 22 CSH randomly received either perindopril 1 mg/kg/day in distilled water (PE. n = 11) or distilled water only (PL. n = 11) and seven control golden Syrian hamsters (C) received distilled water by force-feeding. Compared to C. PL had a lower Vmax. (p < 0.01), a lower amount of α-MHC (p < 0.01). and an unchanged twitch duration. In PE. as compared to PL, there was a higher Vmax. (p < 0.05). a higher α-MHC (p < 0.05). and an unchanged twitch duration. There was a positive relationship between Vmax. and α-MHC in the population taken as a whole (p < 0.01). and when muscles from C and PL groups were plotted together (p < 0.001), but neither within each group, nor when PL and PE were plotted together. Our study indicates that in CSH (a) the preserved contractility with ACE-inhibitor treatment is associated with limitation of isomyosin shift induced by the myopathic process, but no cause-to-effect relationship could he demonstrated on the basis of our data, and (b) adaptive changes in twitch duration were not observed either in untreated CSH or in perindopril-treated CSH. despite significant changes in α-MHC content.

Graft-versus-host reactivity of lymphoid cells from mice genetically selected for high (Hi/PHA) or low (Lo/PHA) responsiveness to phytohemagglutinin

Abstract Lymphocytes from mice genetically selected for high or low responsiveness of their lymphocytes to phytohemagglutinin (Hi/PHA or Lo/PHA) were measured for their proliferative responses to stimulation by alloantigens in a graft-versus-host reaction (GVHR) induced in irradiated allogeneic or semiallogeneic recipients. The high and low responder status of Hi/PHA and Lo/PHA lymphocytes to stimulation by PHA was also observed in GVHR, whatever the haplotype of the host. In contrast, Hi/PHA or Lo/PHA alloantigens produced an almost equivalent GVHR in semiallogeneic recipients. These experiments support the hypothesis that some of the alleles regulating PHA responsiveness intervene in the quantitative regulation of the GVHR.