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Biomedical subjects

M M Struck

Publications and source records attributed to M M Struck.

6 recordsLinked to original sources

Further molecular characterization and stability of the live oral attenuated cholera vaccine strain CVD103-HgR.

Vibrio cholerae CVD103-HgR, the first live attenuated vaccine licensed for human use produced by recombinant DNA technology, was genetically compared to its parent strains 569B and CVD103. The genetic stability for both lyophilized vaccine in final container form and for viable organisms shed from vaccinees was determined. Results obtained lead us to conclude: (i) the genetic composition of the examined genes in CVD103-HgR is identical to that of the parent strains except for the alterations induced; (ii) the level of mercury resistance depends on the orientation of the mer operon within hlyA, with the highest level being observed for the orientation found in CVD103-HgR; (iii) no DNA sequences from plasmids used in construction remain in the genome; (iv) the strain is genetically stable; and (v) both CVD103-HgR and its parent strains contain defective lysogenic prophages. We have further confirmed that a certain amount of restriction fragment length polymorphism (RFLP) exists around the chromosomal ctx locus within V. cholerae strains of the classical biotype (detectable on chromosomal DNA restricted by either HindIII or EcoRI, but not PstI).

Bacterial Vaccines↗

Comparison of X-ray structures of the nucleosome core particle in two different hydration states.

The X-ray structure of the nucleosome core particle was determined at 7 A resolution using crystals containing mixed-sequence DNA and 21% to 27% of 1,6-hexanediol (partially dehydrated crystals). The alcohol was added to the crystals after growth to overcome the non-isomorphism of the crystals and improve the quality of their X-ray diffraction. Here, we report the structure of the nucleosome core particle from these crystals in the absence of the alcohol 1,6-hexanediol at 9 A resolution. The structure, under conditions of nearly full hydration, has been solved by multiple isomorphous replacement methods employing multiple heavy-atom compounds identical to those used for the partially dehydrated structure. The electron density of particles in the two crystal structures is well-correlated throughout the maps and structural elements of the DNA superhelix and histone proteins are generally similar, e.g. the DNA bends sharply at positions +/- 1 and +/- 4 double-helical turns from the DNA center. These results rule out the occurrence of gross structural changes in the 7 A structure due to addition of alcohol. The parts of the nucleosome core particle structure, which are dissimilar between the two forms, can be attributed to differences in molecular packing induced by the addition of 1,6-hexanediol. In contrast to the structure seen in the partially dehydrated crystals, the fully hydrated crystals show a particle in which the H2A-H2B dimers are symmetrically related by the dyad axis found in the H3-H4 tetramer region. However, in the fully hydrated crystals, the first and last double-helical turns of DNA superhelix are not related by dyad symmetry, and one of these segments has reduced contact with the adjacent H2A-H2B dimer.

Fourier Analysis↗

Safety and characterization of the immune response engendered by two combined measles, mumps and rubella vaccines.

We performed a randomized trial to compare the safety and immunogenicity of two combined measles, mumps and rubella vaccines in healthy children 14-24 months of age. Triviraten Berna Vaccine (Swiss Serum and Vaccine Institute), contains the Edmonston Zagreb 19 strain of measles virus, the Rubini mumps virus strain and the Wistar RA 27/3 rubella strain while MMR-Vax (Merck, Sharp & Dohme, West Point, PA) contains the Enders attenuated Edmonston measles strain, the Jeryl Lynn mumps strain and the Wistar RA 27/3 rubella strain. Immunization with Triviraten Berna was associated with a significantly lower incidence of swelling and redness at the injection site in addition to a reduced rate of fever compared with MMR-Vax. Seroconversion rates for the measles and rubella vaccine components were comparable in all tests used. However, seroconversion for the mumps vaccine component was test-dependent. Using an ELISA, the seroconversion rate following immunization with MMR-Vax was significantly (P < 0.01) higher than for Triviraten Berna. In contrast, nearly identical rates were obtained using an indirect immunofluorescence test. Both vaccines were equally effective at engendering antibodies capable of neutralizing wild type mumps virus. Geometric mean ELISA antibody titers against measles and mumps virus were higher following immunization with MMR-Vax while that for rubella was higher after immunization with Triviraten Berna. A small number (N = 13) of adolescents immunized either with MMR-Vax or Triviraten Berna were reimmunized with Triviraten Berna and various humoral and cellular response parameters to the measles and mumps vaccine components analyzed. While few subjects mounted a humoral antibody response to measles, most likely due to elevated baseline titers, there was a marked lymphoproliferative response. Anti-mumps virus ELISA antibody titers were higher both at baseline and after reimmunization in subjects who received MMR-Vax for primary immunization. However, there was no difference in either neutralizing titer or proliferative response in subjects primed with MMR-Vax or Triviraten Berna either before or after reimmunization.

Antibodies, Viral↗