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Biomedical subjects

L Hough

Publications and source records attributed to L Hough.

14 recordsLinked to original sources

Thio and epidithio derivatives of methyl beta-lactoside.

Treatment of methyl beta-lactoside with triphenylphosphine-carbon tetrabromide in pyridine gave the 3',6'-anhydro-6-bromo-6-deoxy derivative, from which 6-thio derivatives were prepared, and methyl 3',4'-O-isopropylidene-beta-lactoside gave the 6,6'-dibromo-6,6'-dideoxy derivative. A dibromide was prepared also from methyl 4',6'-O-benzylidene-beta-lactoside by bromination with Ph3P-CBr4, acetylation, and then treatment with N-bromosuccinimide. Various 6,6'-dithio derivatives were prepared from the 6,6'-dibromide by nucleophilic substitution reactions. Reaction of the 6,6'-dibromide with thiourea led to the 6,6'-epidithio derivative and, with potassium tricarbonate, the bridged 6,6'-trithiocarbonate was formed. The 6,6'-dibromo derivative underwent selective nucleophilic substitution to give a variety of 6'-bromo-6-thio derivatives. Likewise, with azide, the 6-azide was formed first, followed by the 6,6'-diazide and the product of elimination, the 6-azido-5%-ene. Raney nickel-mediated desulphuration of the various 6,6'-dithio derivatives afforded methyl 6,6'-dideoxy-beta-lactoside and desulphuration of the 6'-bromo-6-thio derivatives could be accomplished without reductive dehalogenation to give methyl 6'-bromo-6,6'-dideoxylactoside.

Carbohydrate Sequence

Learning collaboration in a laboratory setting.

Collaboration is a process that contributes in many ways to improved nursing care. Before collaboration can be practiced effectively, the component skills must be learned. This paper describes a course for graduate students that was developed for this purpose. The students learn basic skills in the classroom and apply them to patients in a laboratory setting. An overview of collaboration, the collaboration course, and clinical application is presented.

Aged

Synthesis of 1-deoxy-6-epicastanospermine and 1-deoxy-6,8a-diepicastanospermine.

Extension of the carbon spine of 2,3;4,5-di-O-isopropylidene-beta-D-fructopyranoside by oxidation at C-1 followed by a Wittig reaction using the phosphorane Ph3P = CHCO2Et gave an oct-4-ulose derivative, which was then transformed into the key intermediate 1-azido-1,2,3-trideoxy-D-arabino-oct-4-ulose. Catalytic hydrogenolysis of this azide, followed by reductive amination between the resulting 1-amino substituent and the 4-keto-group then gave a mixture of pyrrolidines. After sulphonylation at the terminal 8-position, the pyrrolidines were then cyclised further between the nitrogen and C-8 to give 1-deoxy-6-epicastanospermine and 1-deoxy-6,8a-diepicastanospermine.

Alkaloids

Plasma fibronectin synthesis in normal and injured humans as determined by stable isotope incorporation.

In humans, plasma fibronectin decreases early after operative injury, burn, or trauma, followed by a rapid restoration with a secondary decline typically observed if such patients become septic. We determined the rate of plasma fibronectin and plasma fibrinogen synthesis in normal subjects and injured patients using a stable isotope incorporation technique with [15N]glycine. During a constant 14-h infusion of [15N]glycine, the enrichment of [15N]glycine in both the free plasma glycine precursor pool as well as the urinary hippurate pool was determined; the latter used as an estimate of intracellular hepatic precursor enrichment. [15N]Glycine enrichment in both plasma fibronectin and fibrinogen was also quantified. The synthesis rate (Js/V) expressed in micrograms per milliliter of plasma per hour and the fractional synthesis rate (FSR) expressed as percentage of the plasma pool produced per day were determined. In normal subjects, the FSR for plasma fibronectin using 15N enrichment into urinary hippurate was 35.35 +/- 1.46%/d, whereas the Js/V was 4.45 +/- 0.19 micrograms/ml plasma per h. In normal subjects, the FSR for plasma fibronectin using 15N enrichment into free plasma glycine was 14.73 +/- 0.63%/d, whereas the Js/V was 1.98 +/- 0.09 micrograms/ml plasma per h. Early (2-3 d) after burn injury, fibronectin synthesis was increased (Js/V = 5.74 +/- 0.36; P less than 0.05), whereas later after injury, fibronectin synthesis began to decline (Js/V = 3.52 +/- 0.24; P less than 0.05) based on 15N enrichment of urinary hippurate. In contrast, the Js/V and FSR of plasma fibrinogen, a well-documented acute-phase plasma protein, revealed a sustained elevation (P less than 0.05) after injury in both the trauma and burn patients. Thus, plasma fibronectin synthesis is elevated early postinjury, which may contribute to the rapid restoration of its blood level. However, once fibronectin levels have normalized, the synthesis of plasma fibronectin appears to decline.

Adult

Transformations of cellobiose derivatives into analogues of lactose.

The preparation of benzyl beta-cellobioside 2,3,6,2',3'-pentabenzoate (2b) via a 4',6'-benzylidene acetal in 27% overall yield from cellobiose is described. This pentabenzoate has been utilised for conventional syntheses of the 6'-amino-, 4'-amino-, and 4',6'-diamino-analogues of lactose, via the 4',6'-dimesylate. In addition, reaction of the pentabenzoate 2b with sulphuryl chloride initially afforded the 6'-chloro derivative, which was then slowly transformed into a mixture of the 4',6'-dichloro-lactoside and an isomer in which the non-reducing ring of the disaccharide had been transformed into a 3',6'-dideoxy-3',6'-dichloro-gulopyranoside. The latter probably arose by neighbouring-group participation by the 3'-benzoloxy group prior to the introduction of the secondary 3'-chloro substituent. The former dichlorocompound was subsequently converted into 4',6'-dideoxy-4',6'-dichloro-lactose. It was found that the rate of nucleophilic displacement at C-4' of a cellobioside was much lower than that for the corresponding alpha-linked disaccharide, maltose. Furthermore, nucleophilic displacement at C-4' of a lactoside was accompanied by substantial elimination, to give the 4'-ene, together with some cleavage of the interglycosidic bond. tthe origins of these effects are discussed.

Cellulose

IgA and IgM cytoplastic inclusions in a series of cases of chronic lymphocytic leukaemia.

Seventy-two cases of typical chronic lymphocytic leukaemia were screened by electron microscopy for the presence of intracytoplasmic immunoglobulin crystals. Immunoglobulin inclusions were found in four cases. Immunofluorescent studies showed that the inclusions contained IgA in two cases and IgM in the other two patients. Lambda light chain specificity was demonstrated in all four cases. The ultrastructure of the inclusions was identical in each patient except that in one of the IgA cases the inclusions were found in the perinuclear cistern in addition to the more usual location within cisternae of rough endoplasmic reticulum. Surface immunofluorescence showed mu heavy chains in the two cases displaying IgM crystal formation, but in the two IgA patients, no alpha heavy chains were demonstrable at the cell surface. The possible significance of these findings is discussed in relation to the existing literature.

Cytoplasm

Some benzylidene acetal derivatives of theophylline nucleosides.

The reaction of some hexopyranosyltheophylline nucleosides with benzaldehyde in the presence of zinc chloride gave the expected benzylidene acetals. Thus, 7-alpha-D-mannopyranosyltheophylline gave the 2',3':4',6'-diacetal as a mixture of diastereoisomers, one of which was isolated. The beta-D-galacto- and beta-D-gluco-pyranosyltheophyllines gave the 4',6'-acetals, which were characterised as 2',3'-diesters. Mild, acidic hydrolysis of 7-(4,6-O-benzylidene-2,3-di-O-mesyl-beta-D-glucopyranosyl)theophylline gave 7-(2,3-di-O-mesyl-beta-D-glucopyranosyl)theophylline, and strongly basic hydrolysis gave 7-(2,3-anhydro-4,6-O-benzylidene-beta-D-allopyranosyl)theophylline. Ring-opening of this 2',3'-epoxide with iodide anion afforded mainly 7-(4,6-O-benzylidene-2-deozy-2-iodo-beta-D-altropyranosyl)theophylline, which was characterised as the 6'-acetate.

Benzylidene Compounds

Some observations on the periodate oxidation of amino compounds.

Various aliphatic and aromatic amines are oxidized by sodium metaperiodate and these reactions have been studied quantitatively in acidic, unbuffered and basic media. Significant differences have been observed between the behaviour of aliphatic and aromatic amines. Certain compounds also behaved differently under acidic and basic conditions. These reactions are related to the periodate oxidation of amino acids and, from observations on a number of glycine derivatives, a reaction mechanism is proposed for this process.

Amines