Reduction of blood serum cholesterol

By feeding a human subject as the sole source of sustenance a defined diet wherein the carbohydrate consists substantially entirely of glucose, maltose or a polysaccharide of glucose, the blood serum cholesterol level of the human subject is substantially reduced. If 25 percent of the carbohydrate is subsequently supplied in the form of sucrose, an immediate increase from the reduced level is observed. The remainder of the defined diet normally includes a source of amino acids, such as protein or a protein hydrolysate, vitamins, minerals and a source of essential fatty acid

Amino acid analysis

The process and apparatus for qualitative and quantitative analysis of the amino acid content of a biological sample are presented. The sample is deposited on a cation exchange resin and then is washed with suitable solvents. The amino acids and various cations and organic material with a basic function remain on the resin. The resin is eluted with an acid eluant, and the eluate containing the amino acids is transferred to a reaction vessel where the eluant is removed. Final analysis of the purified acylated amino acid esters is accomplished by gas-liquid chromatographic techniques

The Gαq/11 Proteins Contribute to T Lymphocyte Migration by Promoting Turnover of Integrin LFA-1 through Recycling

The role of Gαi proteins coupled to chemokine receptors in directed migration of immune cells is well understood. In this study we show that the separate class of Gαq/11 proteins is required for the underlying ability of T cells to migrate both randomly and in a directed chemokine-dependent manner. Interfering with Gαq or Gα11 using dominant negative cDNA constructs or siRNA for Gαq causes accumulation of LFA-1 adhesions and stalled migration. Gαq/11 has an impact on LFA-1 expression at plasma membrane level and also on its internalization. Additionally Gαq co-localizes with LFA-1- and EEA1-expressing intracellular vesicles and partially with Rap1- but not Rab11-expressing vesicles. However the influence of Gαq is not confined to the vesicles that express it, as its reduction alters intracellular trafficking of other vesicles involved in recycling. In summary vesicle-associated Gαq/11 is required for the turnover of LFA-1 adhesion that is necessary for migration. These G proteins participate directly in the initial phase of recycling and this has an impact on later stages of the endo-exocytic pathway

SDF1-Induced Antagonism of Axonal Repulsion Requires Multiple G-Protein Coupled Signaling Components That Work in Parallel

SDF1 reduces the responsiveness of axonal growth cones to repellent guidance cues in a pertussis-toxin-sensitive, cAMP-dependent manner. Here, we show that SDF1's antirepellent effect can be blocked in embryonic chick dorsal root ganglia (DRGs) by expression of peptides or proteins inhibiting either Gαi, Gαq, or Gβγ. SDF1 antirepellent activity is also blocked by pharmacological inhibition of PLC, a common effector protein for Gαq. We also show that SDF1 antirepellent activity can be mimicked by overexpression of constitutively active Gαi, Gαq, or Gαs. These results suggest a model in which multiple G protein components cooperate to produce the cAMP levels required for SDF1 antirepellent activity

Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

Studies on Arginine Peptides. I. Intermediates in the Synthesis of N-Terminal and C-Terminal Arginine Peptides

Tricarbobenzoxy-L-arginine, as its sodium salt, was prepared in strongly alkaline medium via the carbobenzoxylation of L-arginine. This sodium salt, which was in fact a mixture of at least two different isomeric forms, was converted into a mixture of NαN,ω-dicarbobenzoxy-L-arginine and a single pure isomer of sodium tricarbobenzoxy-L-argininate upon treatment with boiling ethanol. Fractionation of these compounds, followed by acidification of the latter material, yielded pure tricarbobenzoxy- L-arginine wherein the basic properties of the guanido group were completely masked. The utility of this compound in the preparation of N-terminal arginine peptides was demonstrated upon its condensation with amino acid benzyl esters, via the mixed carbonic-carboxylic acid anhydride procedure, followed by catalytic hydrogenolysis of the condensation product. In addition, the N-carboxyanhydride procedure was utilized to effect the transformation of tricarbobenzoxy-L-arginine into NωN,ω -dicarbobenzoxy-L-arginine, and of NαN,ω -dicarbobenzoxy-L-arginine into Nω-carbobenzoxy-L-arginine, as well as the benzyl and methyl ester derivatives of the latter. All of these products are of potential value in the synthesis of C-terminal arginine peptides. In this connection, the esters of Nω-carbobenzoxy-L-arginine were employed in the synthesis of the benzyl and methyl esters of tricarbobenzoxy-L-arginyl-Nω-carbobenzoxy-L-arginine. © 1957, American Chemical Society. All rights reserved

Studies on Arginine Peptides. III. On the Structure of Tricarbobenzoxy-L-arginine

The structural elucidation of Nα,Nω,Nω-tricarbobenzoxy-l-arginine has been achieved. Thus, conversion of this compound to the p-nitrobenzyl ester, followed by the treatment with propionic anhydride, led to Nα,Nω,Nω-tricarbobenzoxy-Nω-propionyl-l-arginine p-nitrobenzyl ester. Catalytic hydrogenolysis of the latter yielded Nω-propionyl-l-argmine which, when subjected to the action of acetic anhydride, was converted to Nα,Nω-diacetyl-Nω-propionylanhydroarginine. Cleavage of the latter with water led to N-acetyl-N′-propionylurea and dl-α-acetylaminopiperidone which, upon identification, established the structure of the starting material. The relation of the structure of tricarbobenzoxyarginine to its utility as a peptide intermediate is considered. © 1961, American Chemical Society. All rights reserved

Studies on Arginine Peptides. II. Synthesis of L-Arginyl-L-arginine and other N-Terminal Arginine Dipeptides

Dicarbobenzoxy-L-arginine and tricarbobenzoxy-L-arginine have been utilized for the preparation of a variety of dipeptides containing an N-terniinal arginine residue. The former compound, either as its acid chloridehydrochloride derivative or under the condensing action of dicyclohexylcarbodiimide, was coupled with diethyl L-glutamate and the condensation product subsequently converted to the corresponding free peptide via successive saponification and catalytic hydrogenolysis; the formation of Nα,Nπ-dicarbobenzoxyanhydro-L-arginine accompanied the coupling reaction, an occurrence presumably attributable to the fact that the basicity of the guanido moiety of Nα,Nπdiacylated arginines is not completely masked. No analogous evidence of intramolecular cyclization was revealed in the case of the more exhaustively protected tricarbobenzoxy-L-arginine upon like condensation, via its mixed carbonic-carboxylic acid anhydride derivative, with the benzyl ester derivatives of L-alanine, L-aspartic acid, L-glutamic acid, glycine, L-isoleucine, D-alloisoleucine, 1,-leucine, L-phenylalanine, L-tyrosine and L-valine. Catalytic hydrogenolysis of the tricarbobenzoxy-L-arginylammo acid benzyl esters so procured led to the corresponding dipeptides, which were isolated in high over-all yield. A comparable condensation between tricarbobenzoxy-L-arginine and benzyl Nπ-carbobenzoxy-L-argininate permitted the ultimate synthesis of L-arginyl-L-arginine, which was isolated and characterized as its diflavianate and dipicrolonate derivatives. © 1959, American Chemical Society. All rights reserved