China
Africa
Explore chapters and articles related to this topic
Cardiac Inhibition of Angiotensin Converting Enzyme: Role of Kinins
Published in Malcolm J. Lewis, Ajay M. Shah, Endothelial Modulation of Cardiac Function, 2020
Wolfgang Linz, Gabriele Wiemer, Bernward A. Schölkens
BK and Lys-BK have identical biological actions and are ligands at the G-protein-coupled B2 kinin receptor. Expression cloning of various mammalian and human B1 and B2 kinin receptors has now been performed (Hess et al., 1992; Ma et al., 1994; Menke et al., 1994; McEachern et al., 1991). The vasodilator effects of kinins are mainly mediated through the release of different autacoids, generated by the endothelium. Recently evidence has accumulated showing that the endothelium itself can release kinins (Wiemer et al., 1994). Activation of endothelial B2 kinin receptors leads to the formation of the potent vasodilators and platelet function modulators NO and prostacyclin (PGI2) (Wiemer et al., 1994) by stimulating phospholipases C and A2. In addition, B2 receptor activation can result in the release of endothelium-derived hyperpolarising factor (EDHF) and ATP in some vascular beds (Vanhoutte, 1993).
Molecular Genetic Analyses of Functional Melanoma-Associated Antigens
Published in Henry T. Lynch, Ramon M. Fusaro, Hereditary Malignant Melanoma, 2019
Lloyd H. Graf, Soldano Ferrone
The cloning approaches described previously can be applied with varying degrees of generality as means of addressing the molecular cloning of immunologically defined molecules. For example, successful use of expression-based cDNA cloning strategies relies on the ability of antibodies to recognize unglycosylated microbial translation products; animal cell cDNA expression cloning relies on the nonexpression by host COS cells, of primate antigen homologs immunologically cross-reactive with the human antigen of interest; and transfection-based approaches can succeed only if the epitope(s) that react with the available antibodies are products of single genes of transfectable (⩽50 kb) size. While the 96 kDa MAA/ICAM-1 molecule may be unusual in meeting all of these criteria, it is probable that the gene(s) encoding any given antigen will be subject to isolation by one or more of the approaches.
Identifying and Localizing Gene Expression Important for the Actions of Abused Drugs
Published in Edythe D. London, Imaging Drug Action in the Brain, 2017
This approach also has limitations. Although increasing strides toward identification of neurotransmitter receptor genes are being taken, this area of study is still in its infancy. (Dixon et al., 1986; Bonner et al., 1987; Boulter et al., 1987; Grenningloh et al., 1987; Kobilka et al., 1987, 1988; Lubbert et al., 1987; Masu et al., 1987; Schofield et al., 1987; Sibley et al., 1987). The difficulties encountered in purifying and sequencing the rare membrane protein “drug receptors” have led to development of complex strategies for expression cloning (Jentsch et al., 1990; Schaeffer et al., 1991). Thus, even optimistic pharmacologists would not presume that all of the molecules of relevance for drug abuse have been identified in ligand-binding or other pharmacologic studies.
Investigational drugs in early phase clinical trials targeting thermotransient receptor potential (thermoTRP) channels
Published in Expert Opinion on Investigational Drugs, 2020
Asia Fernández-Carvajal, Rosario González-Muñiz, Gregorio Fernández-Ballester, Antonio Ferrer-Montiel
The first mammalian TRPV was identified by expression cloning searching for the pharmacologically known capsaicin-activated channel [7]. Functional characterization of the cloned receptor revealed that it was gated by noxious heat with an activation threshold of 42°C. This seminal finding provided the underlying molecular mechanism of capsaicin nocifensive effect, i.e. burning sensation [8]. Additional data showed that TRPV1 is a polymodal channel that can also be activated by extracellular acidic pH and membrane depolarization. Furthermore, endogenous substances such as N-arachidonoyl dopamine, leukotriene B, phospholipase C (PLC), and other natural molecules, including resiniferatoxin (RTX), piperine, gingerol, zingerone, camphor, eugenol, ethanol, and spider and jellyfish venom proteins activate TRPV1 as well [9]. Noteworthy, TRPV1 activity strongly desensitizes in the continuous presence of an activating stimulus. Receptor desensitization is a negative feedback mechanism that includes both a gating mechanism driven by channel closure and retrieval of membrane channels. Furthermore, TRPV1 tachyphylaxis is Ca2+-dependent and implies CaM-induced phosphorylation of the receptor and, for long ligand exposure, TRPV1 endocytosis, and degradation in lysosomes [10].
Prospects for a personalized peptide vaccine against lung cancer
Published in Expert Review of Vaccines, 2019
Yoshiro Nakahara, Taku Kouro, Yuka Igarashi, Mamoru Kawahara, Tetsuro Sasada
In PPV targeting shared antigens, vaccine antigen candidates are screened in pre-vaccination blood samples from each patient by assessing cytotoxic T lymphocytes (CTL) precursor frequencies or immunoglobulin G (IgG) titers specific to them. The vaccine antigen candidates consist of 31 human leukocyte antigen (HLA) class I-restricted 9-mer or 10-mer epitope peptides, which were identified mainly through cDNA expression cloning method with tumor-infiltrating T lymphocyte lines [28–32]: 12 peptides for HLA-A2, 14 peptides for HLA-A24, 9 peptides for HLA-A3 supertype (A3, A11, A31, or A33), and 4 peptides for HLA-A26. These 31 candidate peptides were applicable for patients with positive HLA-A2, -A3, -A11, -A24, -A26, -A31 or -A33 alleles, which cover the vast majority of the Japanese population. Up to four HLA class I-restricted peptides are selected from the 31 candidate peptides, based on HLA typing and preexisting immune responses specific to them. Phase I and II clinical trials of PPV have been conducted and reported in patients with various cancers, including castration-resistant prostate cancer [33,34], pancreatic cancer [35,36], biliary tract cancer [37,38], malignant glioma [39], colorectal cancer [40], urothelial cancer [41,42], and lung cancer [43–47] (Table 1).
Development of a Chlamydia trachomatis vaccine for urogenital infections: novel tools and new strategies point to bright future prospects
Published in Expert Review of Vaccines, 2018
Contemporary vaccine studies have expanded upon earlier observations that described the chlamydial Pmps as one class of potentially novel recombinant vaccine C. trachomatis antigens identified by CD4+ and CD8 + T cell expression cloning, serological expression cloning, and an in silico analysis of the C. trachomatis genome [120]. These membrane-bound, surface-exposed chlamydial proteins that mostly contain only T cell epitopes [120] have been the target of closer scrutiny as vaccine candidates since they act as MHC-bound chlamydial protein epitopes recognized by T cells and identifying T cell antigens is of great importance to vaccinology for this intracellular bacterial pathogen. Human studies have indicated that anti- Pmp-specific antibodies are produced in serum in response to Chlamydia infections [121] but also that women who were positive for PmpI were more likely to have upper genital tract infections [122] suggesting that only some of the nine pmp genes of C. trachomatis serovar D may be good potential vaccine candidates to protect humans. Many examples are found in the literature for the use of recombinant Pmps in combination with other chlamydial surface proteins and adjuvants to protect in vivo and in murine models from chlamydial infections. Evidence shows that in the murine transcervical chlamydial infection model a recombinant protein vaccine consisting of four PmpS (PmpEFGH) in combination with MOMP and a Th1 polarizing adjuvant accelerated clearance of Chlamydia [123]. More recently, in a first preclinical evaluation of a recombinant C. trachomatis PmpD (rPmpD) as a candidate chlamydial vaccine in a murine model, strong anti-rPmpD serum and cervico-vaginal IgG antibody titers corresponded with protection against intravaginal C. trachomatis challenge when delivered subcutaneously in combination with a lipid adjuvant that was a TLR4 agonist [124]. Taken together, these data show that Chlamydia outer membrane proteins are important T cell antigens and also that antibodies to chlamydial Pmps play roles in protection against urogenital C. trachomatis infections highlighting the value of these antigens for consideration in chlamydial vaccine development.