Biomedical subjects

E Chiang

Publications and source records attributed to E Chiang.

11 recordsLinked to original sources

PubMed1995

Peptide mimetics of thyrotropin-releasing hormone based on a cyclohexane framework: design, synthesis, and cognition-enhancing properties.

The design and synthesis of peptide mimetics of thyrotropin-releasing hormone (TRH) in which the peptide backbone is entirely replaced by a cyclohexane framework are described. The cis-1,3,5-trisubstituted ring was expected to permit key pharmacophoric groups to adopt conformations consistent with proposed bioactive conformations of the peptide. Compounds were synthesized by a stereoselective synthesis starting from L-glutamic acid. In a behavioral model of cognition in which TRH is active, the mimetics are potent, active compounds, exhibiting oral activity. One analog (26, (1S,3R,5(2S),5S)-5-[[5-oxo-1-(phenylmethyl)-2-pyrrolidinyl]-methyl]-5- [(1H-imidazol-5-yl)methyl]cyclohexaneacetamide) was radiolabeled for binding studies and evaluated in other binding assays and pharmacological tests. Competition binding of 26 vs [3H]MeTRH to rat brain slices suggests a two-site model for ligand binding with IC50's of 1 microM and 3 mM. Direct binding of [3H]-26 shows a biphasic curve with IC50's of 80 and 49 microM, respectively. Further studies would be needed to establish a link between the novel binding site(s) and the behavioral activity of 26 and TRH analogs.

Amino Acid Sequence↗

PubMed1992

Electrophoresis underestimates the concentration of polyclonal immunoglobulins in serum.

The concentration of gamma-migrating immunoglobulins in blood serum was measured in 200 healthy blood donors by two methods, nephelometry and electrophoresis. Nephelometric values were calculated as IgG + IgM + 1/2 IgA because immunoglobulin G (IgG) and immunoglobulin M (IgM) migrate entirely within the gamma region and immunoglobulin A (IgA) is split between the gamma and beta regions. Electrophoretic values were calculated as % gamma x total protein. Gels were scanned with two different densitometers, providing two sets of electrophoretic data. In each case, the correlation between nephelometry and electrophoresis was very good (r = 0.94 and r = 0.96). However, electrophoresis consistently gave lower results than nephelometry (mean = 2.3 g/L and 4.8 g/L lower, respectively). The disparity between these methods was greater as the concentration of immunoglobulins increased. It is concluded that (1) electrophoresis gives a relative but not absolute value of immunoglobulin concentration in serum; (2) nephelometric and electrophoretic values cannot be used interchangeably; and (3) reference ranges for electrophoresis must take into account the densitometer used.

Adolescent↗

PubMed1992

Structure activity of C-terminal modified analogs of Ac-CCK-7.

Previous work indicates that both the C-terminal phenylalanine amide and the tryptophan moieties of cholecystokinin (CCK) are critical pharmacophores for interaction with either the A or B receptor subtypes. We have examined a series of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe33-NH2] (2) in which the phenyl ring of the C-terminal Phe-NH2 has been modified. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors respectively and for anorectic activity after intraperitoneal administration to rats. Substitution of a number of cycloalkyl or bicyclic aryl moieties for the phenyl ring of phenylalanine33 including cyclopentyl (20), cyclohexyl (21), cyclooctyl (23), 2-(5,6,7,8-tetrahydro)naphthyl (26), 2-naphthyl (27), and 1-naphthyl (29) led to analogs with 10-70 times the anorectic potency of 2. The anorectic activity of 21 was blocked by the specific CCK-A receptor antagonist MK-329. Other bulky aliphatic groups in place of the phenylalanine33 aromatic ring such as isopropyl, 2-adamantyl and cyclohexylmethyl gave derivatives similar to 2 in potency. While most of the new compounds were comparable to CCK in binding assays, 23, 26, 27 and 29 were exceptionally potent with IC50s 10(-11)-10(-14) M in the pancreas. Compounds 23 and 29 were further evaluated for their ability to stimulate amylase secretion and found to have potencies similar to that of CCK. The dissociation between potency in the binding and amylase secretion assays suggests that they may interact with a high affinity binding site which is not coupled to amylase secretion. We conclude that CCK receptors possess a generous hydrophobic pocket capable of accommodating large alkyl groups in place of the side chain of phenylalanine33 and that the pharmacological profile of CCK analogs can be tailored by appropriate exploitation of this finding.

Amino Acid Sequence↗

PubMed1985

Respiratory dyskinesia: review and case reports.

Respiratory dyskinesia, the respiratory manifestations of tardive dyskinesia, has been recognized recently by several investigators. The literature is reviewed, two new cases are described, and possible directions for future research are discussed. It was concluded that respiratory dyskinesia is infrequently recognized clinically; more importantly, it may be easily mistaken for other medical disorders.

Adult↗

PubMed1983

Sensitivity to values of the rate constants in a neurochemical metabolic model.

Equations were derived for the instantaneous relative sensitivities of reaction rates (controllability indices) and metabolite concentrations (response indices) to perturbations in the values of rate constants and were used to analyze the behavior of a model of in vivo glutamate metabolism in rat brain. Controllabilities of reversible reactions were found to increase as the values of the corresponding rate constants (i.e., the rate of approach to equilibrium) increased. Response indices generally declined with the metabolic distance between the metabolite and the rate constant, but they were unexpectedly high for reversible reactions with high controllabilities. The transient response of a given metabolite is most sensitive to reactions involving metabolites which are changing most rapidly relative to their respective pool sizes. Rapidly reversible reactions are most important for communication between metabolite pools.

Animals↗

PubMed1982