A sequence of deoxyribonucleic acid of 2.7 times 10-6 to 3.3 times 10-6 daltons which includes the TEM beta-lactamase gene is present on the small plasmid RSF 1030 (R-Amp). This same sequence is present on plasmid derivatives that have received a translocation of deoxyribonucleic acid specifying the TEM beta-lactamase and is also present on naturally occurring plasmids of the F1, F11, N, X, O, I, C, and W incompatibility groups that do not specify ampicillin resistance or specify O-type beta-lactamases.
The human coagulation system continuously generates very small quantities of Factor Xa and thrombin. Current evidence suggests that basal level activation of the hemostatic mechanism occurs via Factor VIIa-dependent activation of Factor X, but direct proof has not been available for the participation of tissue factor in this pathway. To examine this issue, we infused relatively high concentrations of recombinant Factor VIla ( -50 ugg/ kg body wt) into normal chimpanzees and observed significant increases in the plasma levels of Factor IX activation peptide, Factor X activation peptide, and prothrombin activation fragment F,12. Metabolic turnover studies with radiolabeled Factor IX activation peptide, Factor X activation peptide, and F1+2 indicate that elevated levels of the activation peptides are due to accelerated conversion of the three coagulation system zymogens into serine proteases. The administration of a potent monoclonal antibody to tissue factor, which immediately neutralizes function of the Factor VIla-tissue factor complex in vitro, abolishes the activation of Factor X and prothrombin mediated by the infused recombinant protein, and also suppresses basal level activation of Factor IX and Factor X. The above results suggest that recombinant Factor VIla functions as a prohemostatic agent by interacting with endogenous tissue factor sites, but definitive proof will require studies in hemophilic animals using relevant hemostatic endpoints. (J. Clin.
Myelin oligodendrocyte glycoprotein (MOG) is an Ag present in the myelin sheath of the CNS thought to be targeted by the autoimmune T cell response in multiple sclerosis (MS). In this study, we have for the first time characterized the T cell epitopes of human MOG restricted by HLA-DR4 (DRB1*0401), an MHC class II allele associated with MS in a subpopulation of patients. Using MHC binding algorithms, we have predicted MOG peptide binding to HLA-DR4 (DRB1*0401) and subsequently defined the in vivo T cell reactivity to overlapping MOG peptides by testing HLA-DR4 (DRB1*0401) transgenic mice immunized with recombinant human (rh)MOG. The data indicated that MOG peptide 97–108 (core 99–107, FFRDHSYQE) was the immunodominant HLA-DR4-restricted T cell epitope in vivo. This peptide has a high in vitro binding affinity for HLA-DR4 (DRB1*0401) and upon immunization induced severe experimental autoimmune encephalomyelitis in the HLA-DR4 transgenic mice. Interestingly, the same peptide was presented by human B cells expressing HLA-DR4 (DRB1*0401), suggesting a role for the identified MOG epitopes in the pathogenesis of human MS.
We have mapped a regulatory site mediating the hyperproduction of cholera toxin in mutants of Vibrio cholerae strain 569B. Mutations in this locus, called htx, result in the hypertoxinogenic phenotype, as measured by the ganglioside filter assay and immunoradial diffusion. Transposon-facilitated recombination was used to construct improved genetic donors in 569B parental and hypertoxinogenic mutant strains. Subsequent mapping by conjugation indicated that the htx locus was closely linked to the rif, str, and ilv loci of V. cholerae. Analysis of recombinants from these crosses suggested the following gene order: thy str htx 859 on July 31, 2020 by guest
Transposon-facilitated recombination (Tfr) donors of classical Vibrio cholerae strain 162 were constructed by introducing the ampicillin transposon Tn1 into the P conjugative plasmid and the bacterial chromosome. The improved donors mediated high-frequency, polarized transfer of chromosomal genes from origins to confirm the gene orders of the previous classical strain 162 genetic map and to establish its circularity. Significant transfer of linked genes from E1 Tor Tfr donors to classical recipients was demonstrated, and other evidence for genetic relatedness of these two V. cholerae biotypes is discussed.
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