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Biomedical subjects

K Alexander

Publications and source records attributed to K Alexander.

At least 199 records · Page 11Linked to original sources
PubMed1980

Characterization of a factor(s) present in Klebsiella culture filtrates that specifically modifies an HLA-B27-associated cell-surface component.

It has been shown that HLA-B27 lymphocytes from healthy individuals (B27+ ankylosing spondylitis [AS]-), which are not lysed by an antiserum against Klebsiella K43, can be rendered susceptible to lysis after incubation in the culture filtrate of Klebsiella K43. This finding is compatible with a specific modification by a Klebsiella K43-derived soluble factor of a B27-associated lymphoid cell component. Preliminary characterization of the factor has indicated that it is nondialyzable, but it is heat labile at 56 degrees C for 30 min and has a 35,000-50,000 mol wt. The modifying factor activity of the filtrate is destroyed by neuraminidase but not by trypsin and alpha-chymotrypsin. Furthermore, the ability of the factor to convert B27+AS- lymphocytes can be specifically absorbed by B27+AS- lymphocytes, but not by B27+AS+, B27-AS+, or by B27-AS- lymphocytes, which suggests that B27+AS- cells carry a hypothetical receptor which can specifically bind a Klebsiella K43 antigenic determinant. These results imply that the modification by environmental agents of specific major histocompatibility complex-associated gene products may be an important element in the pathogenesis of the HLA-B27-linked seronegative arthropathies.

Antigens, Bacterial↗
PubMed1980

Search for Klebsiella cell wall components cross-reactive with lymphocytes of B27+ AS+ individuals.

It has been suggested that some Klebsiella sp may cross-react with a cell surface determinant on the lymphocytes of B27+AS+ individuals. Studies were undertaken to identify culture filtrates capable of rendering the lymphocytes of B27-positive healthy controls susceptible to lysis by the anti-Klebsiella antiserum. Polyacrylamide gel electrophoresis of cell wall material of Klebsiella K43 prepared by sonication, high-speed centrifugation, and nonidet solubilization, demonstrated the presence of four major protein bands. When antisera raised in rabbits to each of these were tested for their cytotoxic effect on the lymphocytes of B27+AS+ individuals, an antiserum to one component only, of 40-52 K daltons molecular weight, reproduced the activity of the whole serum. Studies on the K43 filtrate indicated that the 'modifying' factor appeared to reside in a 25-50 K dalton component. Immunoelectrophoresis against anti-K43 serum demonstrated overlapping bands in the culture filtrate and the 40-52 K dalton cell wall fraction and these appeared to be identical on immunodiffusion. Antibody to the cell wall component removed both the 'modifying' activity and the appropriate protein band from the filtrate. The results suggest that a 40-52 K dalton component of the Klebsiella K43 cell wall is cross-reactive with a determinant on the lymphocytes of B27+AS+ individuals and is similar to or identical with a modifying factor in K43 culture filtrate which renders the lymphocytes of B27-positive healthy controls susceptible to lysis by anti-Klebsiella antiserum.

Cell Wall↗
PubMed1979

[Evaluation of neck bruits by directional Doppler sonography (author's transl)].

Neck bruits were noticed 86 times in 60 patients. A hemodynamic obstruction of the carotid artery was diagnosed in 22% by Doppler sonography of the supratrochlear artery. The diagnostic directions in case of neck bruits are suggested: 1. In patients with a history of neurological symptoms a pathological Doppler test will be the indication for cerebral angiography. If obstruction of the carotid artery is suspected by clinical examination cerebral angiography should be done in spite of a normal directional Doppler sonography. 2. Cerebral angiography must be done in patients with asymptomatic neck bruits and a pathological Doppler sonography if the patient will undergo a great operation.

Arterial Occlusive Diseases↗
PubMed1978

Three hydroxylations incorporating molecular oxygen in the aerobic biosynthesis of ubiquinone in Escherichia coli.

The biosynthetic origin of the oxygen atoms of ubiquinone 8 from aerobically grown Escherichia coli was studied by 18O labeling. An apparatus was developed which allowed the growth of cells under a defined atmosphere. Mass spectral analysis of ubiquinone 8 from cells grown under highly enriched 18O2 showed that three oxygen atoms of the quinone are derived from molecular oxygen. It was established that the molecular oxygen is incorporated into the two methoxyl groups (at C-5 and C-6) and one of the carbonyl positions of the ubiquinone molecule by demonstrating that only one of the incorporated oxygens will exchange with water under acidic conditions that specifically catalyze the exchange of carbonyl, but not methoxyl, oxygens. That the C-4 carbonyl oxygen is derived from molecular oxygen was shown by the incorporation of three atoms of 18O2 into ubiquinone 8 biosynthesized from added 4-hydroxybenzoic acid. Comparison of ubiquinone 8 and menaquinone 8 from E. coli grown under 18O2 confirmed that the labeled carbonyl oxygen of the [18O2]ubiquinone 8 is incorporated biosynthetically and not by chemical exchange in the cell. It is concluded that the three hydroxylation reactions involved in the pathway for the aerobic biosynthesis of ubiquinone are all catalyzed by monooxygenases. The implications of this study for the anaerobic biosynthesis of ubiquinone 8 in E coli are discussed.

Aerobiosis↗
PubMed1978

Alternative hydroxylases for the aerobic and anaerobic biosynthesis of ubiquinone in Escherichia coli.

The synthesis of ubiquinone under anaerobic conditions was examined in a variety of strains of Escherichia coli K12. All were shown to synthesize appreciable quantities of ubiquinone 8 when grown anaerobically on glycerol in the presence of fumarate. Under these conditions, ubiquinone 8 was in most cases the principal quinone formed, and levels in the range 50--70% of those obtained aerobically were observed. Studies with mutants blocked in the various reactions of the aerobic pathway for ubiquinone 8 synthesis established that under anaerobic conditions three alternative hydroxylation reactions not involving molecular oxygen are used to derive the C-4, -5, and -6 oxygens of ubiquinone 8. Thus, mutants blocked in either of the three hydroxylation reactions of the aerobic pathway (ubiB, ubiH, or ubiF) are each able to synthesize ubiquinone 8 anaerobically, whereas mutants lacking the octaprenyltransferase (ubiA), carboxy-lyase (ubiD), or methyltransferases (ubiE or ubiG) of the aerobic pathway remain blocked anaerobically. The demonstration that E. coli possesses a special mechanism for the anaerobic biosynthesis of ubiquinone suggests that this quinone may play an important role in anaerobic metabolism.

Aerobiosis↗
PubMed1978

Chemical and enzymic studies on the characterization of intermediates during the removal of the 14alpha-methyl group in cholesterol biosynthesis. The use of 32-functionalized lanostane derivatives.

By using cell-free preparations of rat liver it was shown that the removal of the 14alpha-methyl group (C-32) of steroids containing either a delta7(8) or a delta8(9) double bond is attended exclusively by the formation of the corresponding 7,14- and 8,14-dienes respectively (structures of types III and VIII). Cumulative evidence from a variety of experimental approaches had led to the deduction that delta8(14)-steroids are not involved as intermediates on the major pathway of cholesterol biosynthesis. The metabolism of [32-3H]lanost-7-ene-3beta,32-diol (structure of type I) results in the formation of radioactive formic acid, no labelled formaldehyde being formed. By using appropriately labelled species of the compound (I) it was found that the release of formic acid and the formation of 4,4-dimethylcholesta-7,14-dien-3beta-ol (strurcture of type III) were closely linked processes, and that in the conversion of compound (I) into compound (III), 3-beta-hydroxylanost-7-en-32-al (II) is an obligatory intermediate. Both the conversion of lanost-7-ene-3beta,32-diol (I) into 3beta-hydroxylanost-7-en-32-al (II) and the further metabolism of the latter (II) to 4,4-dimethylcholesta-7,14-dien-3beta-ol (III) exhibited a requirement for NADPH and O2. This suggests that the oxidation of the 32-hydroxy group of compound (I) to the aldehyde group of compound (II) does not occur by the conventional alcohol dehydrogenase type of reaction, but may proceed by a novel mechanism involving the intermediacy of a gem-diol. A detailed overall pathway for the 14alpha-demethylation in cholesterol biosynthesis is considered, and proposals about the mechanism of individual steps in the pathway are made.

Animals↗