Biomedical subjects

P R Deitiker

Publications and source records attributed to P R Deitiker.

5 recordsLinked to original sources

PubMed2000

Suppression of experimental myasthenia gravis by monoclonal antibodies against MHC peptide region involved in presentation of a pathogenic T-cell epitope.

We have prepared monoclonal antibodies (mAbs) against an antigen-binding region of I-A, region 62-76 of I-Abeta(b), which is involved in the T-cell participation in the pathogenesis of EAMG. The mAbs reacted with its parent molecules and inhibited the proliferation of disease-related T-cells. Passive transfer of these mAbs suppressed the occurrence of clinical EAMG, which was accompanied by decreased T-cell and Ab responses to tAChR. The results indicated that blocking the function of disease-related MHC by targeting a disease-associated region on MHC molecules could be an effective, straightforward and feasible strategy for immunointervention in MG.

Amino Acid Sequence↗

PubMed1993

Thick filament substructures in Caenorhabditis elegans: evidence for two populations of paramyosin.

The thick filaments of the nematode Caenorhabditis elegans contain two myosin heavy chain isoforms A and B and paramyosin, the products of the myo-3, unc-54, and unc-15 genes, respectively. Dissociation of paramyosin from native thick filaments at pH 6.36 shows a biphasic function with respect to NaCl concentration. Electron microscopy of the remaining structures shows 15-nm core structures that label with monoclonal anti-paramyosin antibody at 72.5-nm intervals. Purified core structures also show 72.5 nm repeats by negative staining. Structural analysis of native thick filaments and dissociated structures suggests that the more dissociable paramyosin is removed radially as well as processively from the filament ends. Minor proteins with masses of 20, 28, and 30 kD cosediment stoichiometrically with paramyosin in purified core structures.

Actin Cytoskeleton↗

PubMed1992

Assembly-dependent phosphorylation of myosin and paramyosin of native thick filaments in Caenorhabditis elegans.

Phosphorylation of the thick filament proteins myosin and paramyosin was studied in Caenorhabditis elegans. We have incubated partially purified, native thick filaments with [gamma 32P] ATP in the presence of 50-750 mM NaCl, pH 6.5-8.0. Myosin heavy chain and paramyosin were phosphorylatable only upon solubilization at 450 mM and higher NaCl concentrations. Under conditions preserving native structures, no phosphorylation of these proteins occurred. The phosphorylation required Mg2+ but was unaffected by cAMP, cGMP or Ca2+. The specific inhibitor of cAMP and cGMP kinase catalytic subunits, H8, inhibits the activity. Sedimentation experiments show that the kinase may associate with but is not an intrinsic component of thick filaments. In C. elegans, phosphorylation by the thick filament associated activity of myosin and paramyosin is dependent upon the state of their assembly.

Adenosine Triphosphate↗

PubMed1992

Accumulation and assembly of myosin in hypertrophic cardiomyopathy with the 403 Arg to Gln beta-myosin heavy chain mutation.

The sarcomeric proteins and organization of cardiac myofibrils appeared intact in multiple unrelated patients with hypertrophic cardiomyopathy. In two subjects demonstrating the missense mutation at position 403 (Arg to Gln) in the beta-myosin heavy chain gene, total myosin and immunoreactive beta-myosin heavy chain levels were similar to those found in other patients with hypertrophic cardiomyopathy and various disease control subjects. No alteration in expression of the cardiac alpha-myosin heavy chain gene was observed. These results are consistent with the examined myosin heavy chain mutation, permitting proper accumulation and assembly of myosin while primarily impairing contractile function. The characteristic myocyte disarray would appear likely to be a secondary consequence of the mutations.

Adolescent↗

PubMedDate not supplied

Preliminary three-dimensional model for nematode thick filament core.

Understanding the structure and the mechanism of assembly of thick filaments have been long-standing problems in the field of muscle biology. Cores which represent the backbones of thick filaments and consist of paramyosin and associated proteins were isolated from the nematode Caenorhabditis elegans. Electron microscopy of negatively stained and frozen hydrated cores was performed. The resulting images were analyzed by computing their Fourier transforms, three-dimensional reconstruction, and by modeling. A preliminary three-dimensional model is proposed in which the paramyosin constitutes an outer sheath of seven subfilaments about a set of inner 54-nm-long tubules which repeat every 72 nm. The subfilaments are not closely packed but require cross-linking by the internal tubules. Each subfilament consists of two strands of paramyosin molecules which are staggered by 72 nm with respect to one another. This stagger introduces a 22-nm gap between consecutive paramyosin molecules in each strand. An offset of the center of the inner tubules relative to the center of the gap of 6 nm was consistent with the images and their transforms. This model suggests that the nonhelical ends of paramyosin and the unpaired gap between adjacent paramyosin molecules contain sites for the interaction with the inner tubular proteins. The molecular interactions at this locus would appear to be critical in the assembly of thick filaments and their regulation.

Amino Acid Sequence↗