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Biomedical subjects

J Andrews

Publications and source records attributed to J Andrews.

At least 199 records · Page 11Linked to original sources
PubMed1990

Maternal cigarette smoking during pregnancy, adiposity, social class, and perinatal outcome in Cardiff, Wales, 1965-1977.

There have been several reports in which maternal nutritional status has been implicated as either a mediating or moderating factor in the relationship between maternal cigarette smoking and birthweight and perinatal survival. Also, there is evidence that the effects of maternal cigarette smoking on both intrauterine growth and fetal viability are more intense among women of lower social status. The well-maintained data set of the Cardiff Births Survey from 1965-1977 afforded an opportunity to review these issues among over 50,000 births in south Wales (the survey took place in Cardiff City through 1973 and subsequently included suburban areas of South Glamorgan). The major findings were: (1) Smoking was much more common with descending maternal social status; (2) among upper status women, smokers had similar or slightly greater mean Quetelet's indices (kg/m2) than nonsmokers. Among lower status women, smokers were considerably thinner than nonsmokers; (3) the greater the adiposity of the mother, the less the association between cigarette smoking and depressed birthweight; (4) perinatal mortality was significantly higher among heavy smokers (10 or more cigarettes a day) than among nonsmokers; and (5) neither the decrease in birthweight nor the excess mortality associated with smoking was greater among those of lower rather than upper social status, except among class I women, among whom smoking was only minimally associated with depressed birthweight. With the inclusion of the South Glamorgan suburban population in the survey after 1974, the excess mortality associated with heavy smoking dropped from 53 to 16%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Relative folate bioavailability from diets containing human, bovine and goat milk.

The present study was designed to determine the relative folate bioavailability from diets containing human, bovine or goat milk and the relative sensitivity of various response criteria used in assessing folate bioavailability. Following a 12-wk depletion period, 16 groups of male rats (n = 5/group) were fed experimental diets with or without 20% milk solids and graded levels of folic acid for 4 wk. Total folates were measured in plasma, erythrocytes, liver and kidney. Bioavailability of dietary folate was determined using slope-ratio statistics. Plasma response was found to be the most sensitive indicator of folate bioavailability based on steepness of slope, goodness of fit (r = 0.96, P less than 0.01) and linearity of response over the entire range of folate intakes. Kidney folate concentration also showed a significant linear relationship to total folate intake (r = 0.69, P less than 0.01). Liver and erythrocyte folate concentrations were not correlated with folate intake (r = 0.33 and r = 0.22, respectively). Using plasma folate as the response criterion, dietary incorporation of human milk significantly enhanced folate bioavailability by 75% (P less than 0.01). With kidney as the response tissue, folate bioavailability from diets containing human and bovine milk was significantly enhanced over milk-free diets. These results show that incorporation of human or bovine milk into diets enhances folate bioavailability and that plasma and kidney folate concentrations are sensitive and specific indicators of folate bioavailability.

Animals↗
PubMed1990

Pharmacokinetics and inflammatory fluid penetration of cefpodoxime proxetil in volunteers.

The pharmacokinetics of cefpodoxime were determined after a single oral dose of 261 mg of cefpodoxime proxetil, equivalent to 200 mg of cefpodoxime, was given to each of six healthy male volunteers. Concentrations in serum, urine, and cantharidin-induced inflammatory fluid were measured by a microbiological assay. The mean peak level in plasma was 2.1 micrograms/ml, attained at a mean time of 2.9 h. The mean half-life of elimination from serum was 2.2 h. The inflammatory exudate was penetrated moderately rapidly, the mean peak level being 1.7 micrograms/ml at 3.5 h. The mean percent penetration of the inflammatory exudate was 103.7. The mean 24-h urine recovery of cefpodoxime was 32.2%. This study suggests that cefpodoxime proxetil taken once or twice daily will be sufficient to treat urinary or systemic infections caused by susceptible pathogens.

Adult↗
PubMed1990

A single-photon emission computed tomography study of hypoperfusion after subarachnoid hemorrhage.

We used single-photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime in 18 studies on 13 patients with subarachnoid hemorrhage to determine whether any changes in cerebral blood flow could be correlated with clinical or computed tomographic evidence of delayed ischemia. Among the seven patients without focal neurologic deficits, regional cerebral hypoperfusion was demonstrated in only one who died. Among the 10 patients with aneurysmal subarachnoid hemorrhage, one died before surgery, and six developed postoperative delayed ischemic deficits, of whom two died. Among the patients with angiographically documented aneurysms, regional hypoperfusion correlated with the presence and severity of delayed neurologic deficits, whereas correlative computed tomographic scans showed either early infarction or no relevant abnormality. This technique facilitates early diagnosis of cerebral tissue hypoperfusion due to vasospasm after subarachnoid hemorrhage.

Cerebral Angiography↗
PubMed1989

A kinetic study of wild-type and mutant dihydrofolate reductases from Lactobacillus casei.

A kinetic scheme is presented for Lactobacillus casei dihydrofolate reductase that predicts steady-state kinetic parameters. This scheme was derived from measuring association and dissociation rate constants and pre-steady-state transients by using stopped-flow fluorescence and absorbance spectroscopy. Two major features of this kinetic scheme are the following: (i) product dissociation is the rate-limiting step for steady-state turnover at low pH and follows a specific, preferred pathway in which tetrahydrofolate (H4F) dissociation occurs after NADPH replaces NADP+ in the ternary complex; (ii) the rate constant for hydride transfer from NADPH to dihydrofolate (H2F) is rapid (khyd = 430 s-1), favorable (Keq = 290), and pH dependent (pKa = 6.0), reflecting ionization of a single group. Not only is this scheme identical in form with the Escherichia coli kinetic scheme [Fierke et al. (1987) Biochemistry 26, 4085] but moreover none of the rate constants vary by more than 40-fold despite there being less than 30% amino acid homology between the two enzymes. This similarity is consistent with their overall structural congruence. The role of Trp-21 of L. casei dihydrofolate reductase in binding and catalysis was probed by amino acid substitution. Trp-21, a strictly conserved residue near both the folate and coenzyme binding sites, was replaced by leucine. Two major effects of this substitution are on (i) the rate constant for hydride transfer which decreases 100-fold, becoming the rate-limiting step in steady-state turnover, and (ii) the affinities for NADPH and NADP+ which decrease by approximately 3.5 and approximately 0.5 kcal mol-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding, Competitive↗
PubMed1989

Interference of electron transport inhibitors with desaturation of monogalactosyl diacylglycerol in intact chloroplasts.

Isolated intact chloroplasts are able to desaturate fatty acids in newly synthesized monogalactosyl diacylglycerol. By analogy with other systems, this desaturation might be expected to involve electron carriers. The effects of electron transport inhibitors on chloroplast lipid-linked desaturation were therefore investigated. Because desaturation occurs in the dark and is not inhibited by compounds specifically blocking photosystem II, it appeared that the photosystems themselves did not participate. Several compounds that prevent enzymatic reoxidation of plastoquinol in thylakoid membranes at the Qz site or withdraw electrons from this lipophilic electron carrier inhibited desaturation in the dark. This inhibition could not be reversed by adding chemicals that donate electrons to photosystem I, indicating that carriers past the cytochrome b/f complex were not involved. Inhibitors of cyclic electron transport interfered with desaturation only at rather high concentrations or not at all. Additional compounds that block the reduction of quinones were slightly inhibitory. Dithioerythritol and KCN also inhibited desaturation, although their exact mode of action is unknown. Dinitrophenyl-iodonitrothymol (DNP-INT), stigmatellin, and myxothiazol did not block desaturation at concentrations that inhibited photosynthetic electron flow through the Qz site very efficiently. Therefore, these results argue against an involvement of the Qz site in desaturation. Accordingly, the inhibition by the other compounds seemingly interfering at the same site as well as that by electron acceptors could be due to interference at a different redox step in desaturation. In vitro these compounds function also as electron acceptors in diaphorase reactions catalyzed by ferredoxin:NADP oxidoreductase.

Acylation↗
PubMed1989

NMR studies of differences in the conformations and dynamics of ligand complexes formed with mutant dihydrofolate reductases.

Two mutants of Lactobacillus casei dihydrofolate reductase, Trp 21----Leu and Asp 26----Glu, have been prepared by using site-directed mutagenesis methods, and their ligand binding and structural properties have been compared with those of the wild-type enzyme. 1H, 13C, and 31P NMR studies have been carried out to characterize the structural changes in the complexes of the mutant and wild-type enzymes. Replacement of the conserved Trp 21 by a Leu residue causes a decrease in activity of the enzyme and reduces the NADPH binding constant by a factor of 400. The binding of substrates and substrate analogues is only slightly affected. 1H NMR studies of the Trp 21----Leu enzyme complexes have confirmed the original resonance assignments for Trp 21. In complexes formed with methotrexate and the mutant enzyme, the results indicate some small changes in conformation occurring as much as 14 A away from the site of substitution. For the enzyme-NADPH complexes, the chemical shifts of nuclei in the bound coenzyme indicate that the nicotinamide ring binds differently in complexes with the mutant and the wild-type enzyme. There are complexes where the wild-type enzyme has been shown to exist in solution as a mixture of conformations, and studies on the corresponding complexes with the Trp 21----Leu mutant indicate that the delicately poised equilibria can be perturbed. For example, in the case of the ternary complex formed between enzyme, trimethoprim, and NADP+, two almost equally populated conformations (forms I and II) are seen with the wild-type enzyme but only form II (the one in which the nicotinamide ring of the coenzyme is extended away from the enzyme structure and into the solvent) is observed for the mutant enzyme complex. It appears that the Trp 21----Leu substitution has a major effect on the binding of the nicotinamide ring of the coenzyme. For the Asp 26----Glu enzyme there is a change in the bound conformation of the substrate folate. Further indications that some conformational adjustments are required to allow the carboxylate of Glu 26 to bind effectively to the N1 proton of inhibitors such as methotrexate and trimethoprim come from the observation of a change in the dynamics of the bound trimethoprim molecule as seen from the increased rate of the flipping of the 13C-labeled benzyl ring and the increased rate of the N1-H bond breaking.

Cloning, Molecular↗
PubMed1989

Measurement of temperature generated by visible-light-cure lamps in an in vitro model.

The dental pulp is vulnerable to cavity preparation and restoration procedures. This vulnerability may be a result of the temperature rise generated by those procedures. When visible-light-cure lamps are used to place composite restorations, they cause the temperature in the pulp to rise. This study measured the temperature rise recorded when six visible-light-cure lamps were tested for 20- and 60-second exposure times. They were also tested in conjunction with an air current passed along the face of the lens in order to lower the temperature. Analysis of the data indicates that the lamps do cause a temperature rise within the pulp chamber--a higher rise the longer the lamp is used. Dentin thickness is important, and air lowers the temperature generated.

Dental Pulp↗
PubMed1989

Dihydrofolate reductase: control of the mode of substrate binding by aspartate 26.

The complex of Lactobacillus casei dihydrofolate reductase with the substrate folate and the coenzyme NADP+ has been shown to exist in solution as a mixture of three slowly interconverting conformations whose proportions are pH-dependent and which differ in the orientation of the pteridine ring of the substrate in the binding site. The Asp26----Asn mutant of L. casei dihydrofolate reductase has been prepared by oligonucleotide-directed mutagenesis and studied by one- and two-dimensional 1H-NMR spectroscopy. NMR studies of the mutant enzyme--folate--NADP+ complex show that this exists to greater than 90% in a single conformation over the pH* range 5-7.1. The single conformation observed corresponds to conformation I (the 'methotrexate-like' conformation) of the wild-type enzyme--folate--NADP+ complex. These observations demonstrate that Asp26 is the ionizable group controlling the pH-dependence of the conformational equilibrium seen in the wild-type enzyme.

Amino Acid Sequence↗
PubMed1989

The hypertensive effect of synthetic glucocorticoids in man: role of sodium and volume.

In previous studies, administration of adrenocorticotrophin (ACTH; 0.5 mg i.m. b.d. for 5 days) to normal subjects produced an adrenally dependent rise in blood pressure (BP) of some 20 mmHg, accompanied by an increase in cardiac output and an increase in plasma volume. The BP and metabolic effects of ACTH (increase in plasma glucose, fall in eosinophils, increase in body weight and urine sodium retention) were reproduced by infusion of the glucocorticoid (GC) cortisol at rates (6-8 mg/h) which reproduced the blood concentrations of the steroid achieved with ACTH administration. Oral administration (hydrocortisone 200 mg daily) produced similar changes qualitatively, although the cortisol concentrations and increase in pressure (12 mmHg) were less. Plasma volume was increased. To determine the role of urine sodium retention and plasma volume expansion in the hypertension, we gave synthetic steroids to six normal subjects for 5 days, at doses which were calculated to be similar for GC activity, but which had little or no mineralocorticoid (MC) activity. Prednisolone (40 mg/day), methylprednisolone (32 mg/day), triamcinolone (40 mg/day) and dexamethasone (8 mg/day) all produced equivalent GC effects (increase in plasma glucose, increase in total white cell count, fall in direct eosinophil count). There were no MC effects with any of the steroids. Body weight did not increase and urinary sodium excretion increased rather than decreased. Plasma volume (125I human serum albumin) and haematocrit were unchanged. BP rose with all four steroids: systolic BP rose by 13 mmHg with prednisolone, by 9 mmHg with methylprednisolone, by 10 mmHg with triamcinolone, and by 6 mmHg with dexamethasone. Diastolic BP increases were 8, 11, 8 and 7 mmHg, respectively. Thus, neither MC activity nor an increase in plasma volume is essential for steroids to induce an increase in blood pressure. Therefore, screening of synthetic GCs to minimize MC activity will not prevent hypertensive complications.

Adult↗