Cord factor isolation

The purification and isolation of cord factor was greatly facilitated by its particular delayed toxicity for mice (upon repeated injections of microgram quantities). For detailed reviews on cord factor, see Refs. 25 and 26. 

Isolation of Cord Factor.—In Bloch s first paper, it had been shown that a petroleum-ether treatment of living bacteria extracts a crude lipid having the particular toxicity of cord factor. As the yield in these extractions was rather low, other lipid fractions extracted from whole bacilli were examined and it was found that cord factor is present in preparations of wax C and wax D —principally, however, in the former. 

Pure cord-factor was finally isolated by repeated chromatography on magnesium silicate, silicic acid, and silica gel. From the H37 Rv strain and from BCG, cord factor was obtained as a colorless wax, melting at about 40°, [ ]d -f 30°. 

A toxic lipid isolated by Spitznagel and Dubos by extraction of Mycobacteria with monochlorobenzene has been shown to contain cord factor as the only active compound. ... 

Cord Factor Trehalose 6,6-dimycolaie 6.6 -di-0-mycolyl -a,a-trehalose (6-O-mycolyl -dr-D-glucopyranos-yl) 6-0 mycolyl-ot-D-glucopyranoside Toxic glycolipjds responsible for the cord formation and the leukotoxic effect of virulent bacilli. The term cord factor is widely used for the natural mixture of trehalose dimycolates produced by virulent Mycobacteria, Nocardia, Corynebacteria and attenuated BCG, q.v. For precise designation, the strain from which the preparation was isolated must be mentioned. First isolated from Mycobacterium tuberculosis H. Bloch, J. Exp. 

The presence of trehalase in the tubercle bacillus was discovered by Bloch and SuUman in 1945. Optimal hydrolysis of a,a-trehalose by the enzyme occurred in acid to neutral solutions. Since a,a-trehalose is not utilized by the bacteria so rapidly as is n-glucose, it was inferred that the bacillus only metabolizes the a, -trehalose after the trehalase has converted it into D-glucose. Trehalosamine (see p. 220) has an antimycobac-terial effect. This effect is antagonized by a,a-trehalose. One mole of trehalosamine as inhibitor removes 0.337 mole of Q ,a-trehalose from the surface of the enzyme. Total inhibition of mycobacterial trehalase is not readily produced. Cord factor was also isolated from wax D of a BCG strain of M. tuberculosis in 1959 by Nojima. A list of fatty acid esters of a, a-trehalose is given in Table I. 

Infection with mycobacteria appears to stimulate the immunity of the host to tumours. Isolated cell walls also provide some antitumour activity but treatment with proteolytic enzymes or organic solvents destroys the tumour-suppressive properties of the walls. Subsequent addition of cord factor restores this activity. 

Somatostatin (or somatotropin release-inhibiting factor [SRIF]) occurs primarily as a 14-amino acid peptide, although a 28-amino acid form also exists. As with the other hypothalamic peptides, it is formed by proteolytic cleavage of a larger precursor. Somatostatin, originally isolated from the hypothalamus, is also in many other locations, including the cerebral cortex, brainstem, spinal cord, gut, urinary system, and skin. Somatostatin inhibits the secretion of many substances in addition to growth hormone (Table 59.1). 

Two distinct factors have been isolated from muscle and spinal cord which clearly promote motoneuron survival and there is synergy between these factors (Dohrmann et al., 1987). Naturally occurring cell death is enhanced in sympathetic and parasympathetic ganglia after blockade of ganglionic neurotransmission with pem-pidine (Hendry, 1973 Maderdrut et al., 1988). On the other hand blockade of activity of the target with curare leads to an increase in survival of mo-... 

Special morphogenetic factors seem also to exist in other induction systems. In all vertebrate embryos organogenesis of the cartilageneous vertebral column has been found to depend on the inductive activity of the spinal cord and the notochord (Strudel, 1967). Semitic mesenchyme isolated from early chick embryos does not form cartilage in contrast to somites taken from older embryos. In isolated somitic mesenchyme from 2- to 3-day-old embryos the formation of cartilage can be induced by extracts from spinal cord and notochord (Strudel, 1962). The chemical nature of the inducer is not yet known. Metachromatic... 

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