Absence Of Promoters Research Articles

Intranasal administration of calcitonin and of other peptides: Studies with different promoters

Peptide hormones can only be administered by the injective route, not by the oral route: injective therapy has several drawbacks, being non physiologic, poorly reproducible and with a poor patient compliance over prolonged treatments. This explains the interest for alternative routes of peptide administration, in particular for the intranasal route. Intranasal administration of peptides with a short molecule (10 amino acids or less) is now routinely performed in the clinical setting, although their bioavailability is low. In order to be absorbed through the nasal mucosa peptides like insulin, glucagon, GHRH and CRH require the presence of substances, called surfactants or promoters. Salmon calcitonin (sCT) is readily absorbed and shows appreciable metabolic effects and clinical efficacy, with a clear dose-effect ratio both in normal subjects and in post-menopausal women: some data also show a similar effect of sCT and carbicalcitonin. Human calcitonin (hCT) has a lower biological efficacy than sCT and is poorly absorbed: various promoters allow significant nasal absorption and preliminary data show a significant clinical efficacy of hCT thus administered. Also glucagon is absorbed through the nasal mucosa only in the presence of promoters and exerts clear metabolic effects in patients with hypoglycaemia. Surfactants are potentially toxic, so that new approaches are required: poor solubility and polymerization might be responsible for poor nasal absorption: however, cyclodextrins that enhance solubility, were without effect on absorption of glucagon: similarly, monomeric insulin was not absorbed in the absence of promoters. At present, the use of promoters seems justified only for peptides with a poor spontaneous absorption.

Transcription Elongation Factor SII (TFIIS) Enables RNA Polymerase II to Elongate through a Block to Transcription in a Human Gene in Vitro

Elongation and termination by RNA polymerase II are important regulatory steps for eukaryotic gene expression. We have previously studied the transcription of linear DNA templates where specific initiation of transcription by highly purified RNA polymerase II can be achieved in the absence of promoters and promoter-specific factors. Using these templates we have shown that a human histone gene, H3.3, contains sequences (intrinsic terminators) within which purified RNA polymerase II will efficiently terminate transcription (Reines, D., Wells, D., Chamberlin, M.J., and Kane, C. M. (1987) J. Mol. Biol. 196, 299-312). Curiously, these signals were found within an intron, 3'-untranslated, and protein-encoding regions of the gene suggesting that they might act to attenuate transcription of H3.3 in vivo. Here we show that intrinsic terminator sequences from an H3.3 gene intron also block in vitro transcript elongation by RNA polymerase II when the enzyme has initiated transcription from a promoter using highly purified transcription initiation factors. However, under the conditions used for promoter-specific transcription there is little transcript release. Instead the polymerase can pause at these sites for periods exceeding 60 min. We have identified and partially purified an activity from HeLa cells that causes the transcription complex to read through this block to transcription elongation. This readthrough activity fractionates with a previously characterized elongation factor (SII) over three chromatographic columns. A homogeneous preparation of calf thymus SII can also provide this activity in trans. This factor may facilitate passage of the RNA polymerase II transcription complex through such intragenic sites in cellular genes in vivo.

A single crystal study of the silver-catalysed selective oxidation and total oxidation of ethylene

Ethylene oxidation has been investigated on a well-characterised Ag(111) single crystal surface at pressures of up to 50 Torr. In the absence of promoters and moderators, chemisorbed atomic oxygen reacts with adsorbed ethylene to yield both ethylene oxide and (CO 2 + H 2O). Chemisorbed dioxygen, though present, appears to play no direct role in either of these reactions; the presence of subsurface oxygen is necessary for selective oxidation but not for total oxidation. Batch reactor studies yield rate parameters for both partial and total oxidation which are consistent with the values reported for conventional supported catalysts; selectivity decreases with increasing temperature, pressure, and ethylene coverage. Acetaldehyde, acetic acid, and oxalic acid are identified as reaction intermediates in the pathway to CO 2 formation. Results for the oxidation of C 2D 4 confirm these observations, and the observed kinetic isotope effect indicates that H-transfer rather than CC cleavage is rate-determining in the combustion of both ethylene and ethylene oxide. Possible reaction pathways and mechanisms are examined.

Molecular rearrangements. III. Thermal decomposition of some selected thioesters

Four selected thioesters (1–4) were prepared and pyrolyzed in the absence of promoters either alone or in isoquinoline solvent. These esters include benzyl thiobenzoate (1), phenyl phenylthioacetate (2), benzyl phenylthioacetate (3), and phenyl thiobenzoate (4). Pyrolysis of 1 gave mainly 2,3,4,5-tetraphenylthiophene in addition to benzene, biphenyl, benzyl thiol, and benzoic acid. Thermal decomposition of 1 under nitrogen gave benzaldehyde, benzil, and only a trace of benzoic acid in addition to the former products. Compound 2 afforded essentially toluene and dibenzyl in addition to benzene, biphenyl, phenyl sulphide, thiophenol, and phenyl acetic acid. Thermolysis of 3 gave toluene and stilbene beside small quantities of benzyl thiol and phenylacetic acid. Finally, thermal decomposition of 4 in isoquinoline gave benzene, biphenyl, phenyl sulphide, thianthrene, thiophenol, benzoic acid, and 1-phenylisoquinoline. H2S and CO are also produced in all cases. In these rearrangements, the C—S bonds undergo homolytic fission either simultaneously or selectively. No isomer redistribution precedes the coupling reactions. Plausible mechanisms for the above facts are proposed.

Thermolysis of mono-, di- and tri-benzylamines, IV

Thermolysis of mono-, di- or tri-benzylamine for some days in the absence of promoters gave the same products: ammonia, toluene, dibenzyl, stilbene and benzaldehyde. Thermolysis of dibenzylamine in isoquinoline as a solvent gave 1-benzyl-isoquinoline together with the normal pyrolysis products. When naphthalene and 2-naphthol are used as solvents, benzylation of the solvent nuclei was observed to give 1- and 2-benzylnaphthalenes and 1-benzyl-2-naphthol respectively. In conclusion, thermolysis of tri-, di- or mono-benzylamines proceeds through a free radical mechanism with successive conversions of the tertiary, through secondary to primary alkylamines resulting in the same pyrolysis products.

Organ culture of osteopetrotic (ia) rat bone: evidence that the defect is cellular.

Calvarial bone from osteopetrotic (ia) rats and normal littermates has been cultured in a chemically defined medium supplemented with homologous serum to test for the presence of inhibitors or the absence of promoters of bone resorption in mutant serum. In addition, the response of mutant and normal bone to parathyroid extract and hydrocortisone was tested in vitro. The results indicate that mutant and normal serum do not differ with respect to their ability to support bone resorption and that ia bone responds to hydrocortisone but not parathyroid extract in organ culture. These data indicate that the skeletal defect in ia rats is not humoral but cellular.

Investigation of the vapor-phase hydrolysis of chlorobenzene in presence of a phosphate catalyst

1. The vapor-phase hydrolysis of chlorobenzene in presence of phosphate catalysts was investigated. The activity of a one-component phosphate catalyst in the absence of promoters was confirmed. 2. The influence of the temperature on the degree of conversion of chlorobenzene and on the selectivity of the reaction was investigated. It was found that the phosphate catalyst has a higher thermal stability than silica gel and is less sensitive to the deactivating action of inorganic impurities. 3. It is suggested that the mechanisms of vapor-phase hydrolysis are the same in presence of phosphate and silica gel catalysts.

CLXXXIV.—Low temperature oxidation at charcoal surfaces. Part I. The behaviour of charcoal in the absence of promoters

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