Angiotensin II receptor blockers.
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Angiotensin Receptor Antagonists↗
Biomedical subjects
H Thai
Publications and source records attributed to H Thai.
Influence of autoimmune ovarian disease pathogenesis on ZP3 contraceptive vaccine design.
Zona pellucida (ZP) glycoproteins possess sperm receptor-binding activities. Antibodies against ZP can block sperm-egg interaction and thereby prevent fertilization. The feasibility of developing a safe contraceptive vaccine based on the ZP has been hampered by the finding that active immunization with autologous or heterologous ZP proteins results in infertility that is associated with ovarian dysfunction. A mouse model was used to investigate mechanisms of the ovarian pathology that is induced by active immunization with a 13mer peptide derived from mouse ZP3 (mZP3(330-342)). This peptide includes one native B-cell epitope and two nested T-cell epitopes. Ovarian pathology could be transferred into naive recipients by CD4+ T cells, but not by antibodies, from immunized mice, suggesting the importance of T cells in the mechanism of ovarian pathogenesis. Moreover, immune responses, as well as disease induction, were restricted to H-2a,k,u,s,axb haplotypes. On the basis of this mouse model, a strategy to generate a contraceptive anti-ZP antibody response without a pathogenic T-cell response, irrespective of H-2 haplotype, is described. The B-cell epitope was modified by amino acid substitution to eliminate the overlapping oophoritogenic T-cell epitope, and was linked to a promiscuous foreign T-cell epitope, bovine RNase94-104. The resultant chimaeric peptide (CP2) induced anti-ZP antibodies in 100% of the eight strains of inbred mice with different H-2 haplotypes without significant disease induction. An antifertility trial in B6AF1 female mice immunized with CP2 showed that the anti-ZP antibody was associated with a reduction in fertility. This infertility was reversed with a decline in anti-ZP antibody titre. Preliminary data show that this strategy of vaccine design may also be applied to primates.
Amino Acid Sequence↗
A zona pellucida 3 peptide vaccine induces antibodies and reversible infertility without ovarian pathology.
Zona pellucida 3 (ZP3) is a major glycoprotein of the zona pellucida that possesses the sperm receptor function. ZP3 induces autoantibody that can block sperm/oocyte interaction. However, the feasibility of a ZP3 contraceptive vaccine has been marred by the finding that ZP3-specific T cells mediate ovarian autoimmune disease. Moreover, as reported in this work, only some inbred mouse strains respond to the ZP3 peptide. We now describe a chimeric peptide that induces Abs to native ZP3 regardless of the MHC haplotype of the inbred mice tested. Study in one mouse strain resulted in reduction in fertility that correlates well with zona pellucida Ab titer, and most importantly, the mice do not develop concomitant autoimmune oophoritis. Moreover, the infertility was completely reversible. The design of the vaccine chimeric peptide is governed by the inclusion of two essential components: 1) a promiscuous foreign T cell peptide capable of eliciting a Th cell response regardless of the MHC haplotype of the animals, and 2) the native B cell peptide of ZP3 that has been modified by substitution of residue(s) critical for T cell but not B cell response to ZP3.
Amino Acid Sequence↗
Partial sequence analysis of 130 randomly selected maize cDNA clones.
As part of a project to identify novel maize (Zea mays L. cv B73) genes functionally, we have partially sequenced 130 randomly selected clones from a maize leaf cDNA library. Data base comparisons revealed seven previously sequenced maize cDNAs and 18 cDNAs with sequence similarity to related maize genes or to genes from other organisms. One hundred five cDNAs show little or no similarity to previously sequenced genes. Our results also establish the suitability of this library for large-scale sequencing in terms of its large insert size, proper insert orientation, and low duplication rate.
Cloning, Molecular↗