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Biomedical subjects

A I Scott

Publications and source records attributed to A I Scott.

At least 73 records · Page 4Linked to original sources
PubMed1994

Short-term effects of electroconvulsive treatment on the uptake of 99mTc-exametazime into brain in major depression shown with single photon emission tomography.

Fifteen patients with major depression who were being treated with bilateral electroconvulsive treatment (ECT) were investigated before and 45 min after a single ECT using split-dose Single Photon Emission Tomography (SPET or SPECT) with 99mTc-Exametazime. All patients suffered from unipolar depressive illness and were rated on the Newcastle scale and with the 17-item Hamilton scale. They completed tests of orientation and verbal memory on the day of ECT. For comparison, verbal memory was also tested on the preceding day. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Significant decreases in tracer uptake were confined to the inferior anterior cingulate cortex. The changes were correlated with the severity of depressive symptoms and more weakly with decrements of memory function produced by ECT; there was no significant correlation with stimulus intensity or electroencephalographic measures of seizure duration.

Aged↗
PubMed1994

Genetically engineered synthesis of precorrin-6x and the complete corrinoid, hydrogenobyrinic acid, an advanced precursor of vitamin B12.

BACKGROUND: Genetically engineered synthesis, in which the gene products, cofactors, and substrates of a complete pathway are combined in vitro in a single flask to give the target, can be a viable alternative to conventional chemical construction of molecules of complex structure and stereochemistry. We chose to attempt to synthesize the metal-free corrinoid hydrogenobyrinic acid, an advanced precursor of vitamin B12. RESULTS: Cloning and overexpression of the genes necessary for the S-adenosyl methionine dependent conversion of 5-aminolevulinic acid (ALA) to precorrin-3 and those required for the synthesis of hydrogenobyrinic acid from precorrin-3 completed the repertoire of the 12 biosynthetic enzymes involved in corrin synthesis. Using these enzymes and the necessary cofactors, the multi-enzyme synthesis of hydrogenobyrinic acid from ALA can be achieved in 20% overall yield in a single reaction vessel, corresponding to an average of at least 90% conversion for each of the 17 steps involved. CONCLUSIONS: By replacing the cell wall with glass, and by mixing the soluble biosynthetic enzymes and necessary cofactors, the major segment of the physiological synthesis of vitamin B12 has been accomplished. Since only those enzymes necessary for the synthesis of hydrogenobyrinic acid from ALA are supplied, none of the intermediates is deflected from the direct pathway. This results in an efficiency which in fact surpasses that of nature.

Escherichia coli↗
PubMed1994

Evidence for an intermediate in the enzymatic formation of uroporphyrinogen III.

Evidence for an azafulvene intermediate in the enzymatic formation of Uroporphyrinogen III has been obtained. Using conditions to slow down the enzyme activity (high pH, low temperature), the transient species was trapped with ammonium ions as aminomethylbilane and with sodium borohydride as methylbilane, and observed by 13C-NMR.

Escherichia coli↗
PubMed1994

Genetically engineered synthesis of natural products.

The feasibility of multi-step, one-flask total synthesis of natural products is demonstrated by cloning and overexpression of the corresponding biosynthetic enzymes from plant and microbial sources. As many as eight or nine enzymes can be recombined in vitro to reach an advanced intermediate in the vitamin B12 pathway.

Amino Acid Sequence↗
PubMed1994

Is there a delay in the onset of the antidepressant effect of electroconvulsive therapy?

The severity of depression in 11 drug-free unipolar patients diagnosed with definite major depressive disorder was assessed using the Hamilton Rating Scale for Depression during a course (5-10 treatments) of bilateral electroconvulsive therapy (ECT). The degree of improvement after three treatments of ECT was six times greater than the improvement that occurred over the remainder of the course. Although depressed patients who recover with ECT require repeated treatments, the treatments early in a course of ECT can have marked antidepressant effect.

Adult↗
PubMed1993

The Escherichia coli cysG gene encodes the multifunctional protein, siroheme synthase.

Previously, the E. coli cysG gene product had been shown to sequentially methylate uro'gen III to produce precorrin-2, hence it was given the trivial name uro'gen III methylase. We now report that in addition to methylase activity, the CysG protein catalyses both the NAD+ dependent oxidation of precorrin-2 to sirohydrochlorin, but also the insertion of iron into this oxidized intermediate, thereby producing siroheme. Thus CysG is a multifunctional protein solely responsible for siroheme synthesis from uro'gen III in E. coli, and accordingly is renamed siroheme synthase.

Amino Acid Sequence↗
PubMed1993

Biosynthesis of vitamin B12. Discovery of the enzymes for oxidative ring contraction and insertion of the fourth methyl group.

In the vitamin B12 biosynthetic pathway the enzymes responsible for the conversion of precorrin-3 to precorrin-4 have been identified as the gene products of cobG and cobJ from Pseudomonas denitrificans. CobG catalyzes the oxidation of precorrin-3 to precorrin-3x (a hydroxy lactone) whereas CobJ is a SAM-dependent C-17 methyl transferase and is necessary for ring contraction. A mechanism for ring contraction is proposed.

Bacterial Proteins↗
PubMed1993

Sequence of the Candida albicans erg7 gene.

The nucleotide sequence of the Candida albicans erg7 gene, which complements erg7 mutants of Saccharomyces cerevisiae and restores oxidosqualene cyclase activity, was determined. The gene encodes a 728-aa protein that displays homology with squalene-hopene cyclase, providing further evidence that erg7 is the gene encoding 2,3-oxidosqualene cyclase.

Amino Acid Sequence↗
PubMed1993

Interaction of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 17 beta-estradiol in MCF-7 human breast cancer cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 12-O-tetradecanoylphorbol-13-acetate (TPA) are both tumor promoters which act through different mechanisms. In MCF-7 human breast cancer cells, both TCDD and TPA inhibited constitutive and 17 beta-estradiol-induced cell proliferation but showed no apparent interactive effects. TCDD also inhibited the 17 beta-estradiol-induced secretion of the 52-kDa protein (procathepsin D) and induced CYP1A1 gene expression whereas TPA alone was inactive for these responses. Moreover, TPA did not modulate the TCDD-mediated antiestrogenic or induction responses and did not decrease levels of the nuclear Ah receptor complex as determined in a gel mobility shift assay using a 32P-dioxin responsive element (DRE). The interactions of TPA and TCDD on the metabolism of [13C]glucose to [13C]lactate was also investigated using 13C-nuclear magnetic resonance spectroscopy. The rate of formation of [13C]lactate from [13C]glucose in MCF-7 cells treated with DMSO (control), 1 nM 17 beta-estradiol, 1 nM TCDD, 1 nM TCDD plus 1 nM 17 beta-estradiol, and 0.1 ng/ml TPA plus 1 nM 17 beta-estradiol was 28, 48, 20, 22 and 50 fmol lactate formed/cell/h, respectively. Thus, TCDD, but not TPA, inhibited this estrogen-induced response. However, a comparison of the rate of lactate formation in cells treated with TCDD plus 17 beta-estradiol (22 fmol/cell/h) or TCDD plus 17 beta-estradiol plus TPA (61 fmol/cell/h) showed that TPA significantly inhibited the TCDD-mediated antiestrogenic response. The results of these studies in MCF-7 cells demonstrate that the interactions of TCDD and TPA are highly response-specific and do not involve TPA-mediated downregulation of the nuclear Ah receptor complex.

Base Sequence↗
PubMed1993

New sesquiterpene alpha-methylene lactones from the Egyptian plant Jasonia candicans.

Extracts of the plant Jasonia candicans possess antimicrobial activity. ET2O/MeOH extracts were subjected to liquid chromatography, and several sesquiterpenes were isolated and identified including the known compounds confertin [1], 4,11(13)-eudesmadien-12-oic acid [2], and 11-eudesmen-4-ol [3]. Two new diol alpha-methylene lactone antimicrobial agents were identified from nmr and mass spectral data and X-ray crystallography as (4 alpha, 5 alpha, 8 beta, 10 beta)-4,10-dihydroxy-1,11(13)-guaidien-12,8-olide [4] and (4 alpha, 5 alpha, 8 beta, 10 alpha)-4,10-dihydroxyl-1,11 (13)-guaidien-12,8-olide[5], which differ in stereochemistry at the C-10 tertiary alcohol center.

Lactones↗
PubMed1992

Expression of 9 Salmonella typhimurium enzymes for cobinamide synthesis. Identification of the 11-methyl and 20-methyl transferases of corrin biosynthesis.

Nine of the cbi genes from the 17.5 kb cob operon of Salmonella typhimurium previously shown by genetic studies to be involved in the biosynthesis of cobinamide from precorrin-2, have been subcloned and expressed in Escherichia coli. Seven of the gene products were found in the soluble fraction of cell lysates and have been purified. The gene products corresponding to cbi E, F, H and L were shown by SAM binding and by homology with other SAM-binding proteins to be candidates for the methyltransferases of vitamin B12 biosynthesis. The enzymatic functions of the gene products of cbiL and cbiF are associated with C-methylation at C-20 of precorrin-2 and C-11 of precorrin-3.

Amino Acid Sequence↗
PubMed1992

Edinburgh primary care depression study: treatment outcome, patient satisfaction, and cost after 16 weeks.

OBJECTIVE: To compare the clinical efficacy, patient satisfaction, and cost of three specialist treatments for depressive illness with routine care by general practitioners in primary care. DESIGN: Prospective, randomised allocation to amitriptyline prescribed by a psychiatrist, cognitive behaviour therapy from a clinical psychologist, counselling and case work by a social worker, or routine care by a general practitioner. SUBJECTS AND SETTING: 121 patients aged between 18 and 65 years suffering depressive illness (without psychotic features) meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition for major depressive episode in 14 primary care practices in southern Edinburgh. MAIN OUTCOME MEASURES: Standard observer rating of depression at outset and after four and 16 weeks. Numbers of patients recovered at four and 16 weeks. Total length and cost of therapist contact. Structured evaluation of treatment by patients at 16 weeks. RESULTS: Marked improvement in depressive symptoms occurred in all treatment groups over 16 weeks. Any clinical advantages of specialist treatments over routine general practitioner care were small, but specialist treatment involved at least four times as much therapist contact and cost at least twice as much as routine general practitioner care. Psychological treatments, especially social work counselling, were most positively evaluated by patients. CONCLUSIONS: The additional costs associated with specialist treatments of new episodes of mild to moderate depressive illness presenting in primary care were not commensurate with their clinical superiority over routine general practitioner care. A proper cost-benefit analysis requires information about the ability of specialist treatment to prevent future episodes of depression.

Adolescent↗
PubMed1992

Enzymatic synthesis and structure of precorrin-3, a trimethyldipyrrocorphin intermediate in vitamin B12 biosynthesis.

The trimethylated intermediate of vitamin B12 (corrin) biosynthesis, precorrin-3, was produced from various 13C-enriched isotopomers of 5-aminolevulinic acid (ALA), using a multiple-enzyme system containing ALA dehydratase, porphobilinogen deaminase, uro'gen III synthetase, and the S-adenosyl-L-methionine-(SAM)-dependent uro'gen III methyltransferase (M-1) and precorrin-2 methyltransferase (M-2) in the presence of [13C]SAM. Structural analysis of the resulting product, precorrin-3, reveals a close similarity to precorrin-2 but with several subtle differences in the conjugated array of C = C and C = N bonds which reflect the presence of the new C-methyl group at C20 and its influence on the electronic distribution in the dipyrrocorphin chromophore. The implications of this structure for corrin biosynthesis are discussed.

Escherichia coli↗