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Biomedical subjects

D Lyons

Publications and source records attributed to D Lyons.

At least 73 records · Page 4Linked to original sources
PubMed1993

The haemodynamic effects of GR 32191, a thromboxane A2 receptor antagonist, in patients with renal artery stenosis and hypertension.

This study was designed to determine if GR 32191 a thromboxane A2 receptor antagonist, would lower blood pressure in patients with hypertension and renal artery stenosis. Eight patients with unilateral atheromatous renal artery stenosis and hypertension were studied in a double-blind, single dose, placebo controlled, crossover study. The results show that, GR 32191, given orally, in doses of 20 mg and 40 mg, does not reduce the blood pressure to any clinically important degree.

Aged↗
PubMed1993

Conformation of glutathione adduct and oxidized forms of platelet-derived growth factor.

The conformational properties of several platelet-derived growth factors (PDGFs) were characterized by circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR), gel filtration and sedimentation equilibrium. Three different forms of disulfide linked dimer, PDGF-AA, PDGF-AB, and PDGF-BB, showed similar far UV CD spectra with evidence for slight beta-structure, but little evidence of other regular secondary structures. These spectra were, however, different from the far UV CD spectra of the glutathione adducts of PDGF-A and B, suggesting that the latter two proteins adopt different conformations in the absence of intra- or inter-molecular disulfide bonds. FTIR studies confirmed this by showing that the glutathione adducts of the PDGF-B protein have a significantly lower amount of regular secondary structures than PDGF-BB. Additionally, the increased bandwidths of the amide I components of the FTIR spectrum of the glutathione adduct indicates a more flexible structure relative to the dimeric form. Sedimentation equilibrium analysis showed that PDGF-BB is primarily a dimer and that the glutathione form is primarily a monomer. Thus, it was concluded that the glutathione derivative has little affinity to form non-covalent dimers in neutral solution.

Chromatography, Gel↗
PubMed1992

Cysteine to serine substitutions in basic fibroblast growth factor: effect on inclusion body formation and proteolytic susceptibility during in vitro refolding.

We have investigated the effect of cysteine to serine substitutions in human basic fibroblast growth factor (bFGF) on the formation of inclusion bodies in Escherichia coli. Using a temperature-sensitive expression, system, about 30% of human bFGF, which contains four cysteines at positions 26, 70, 88, and 93, is deposited into inclusion bodies. A single mutation at position 88 and a double mutation at positions 70 and 88 do not greatly alter the partition of bFGF into soluble and insoluble cell fractions. However, a single substitution of cysteine 70 by serine decreases the fraction of soluble bFGF significantly. When cysteines 26 and 93 (conserved among related growth factors) are replaced by serines, no soluble bFGF is formed in E. coli. Cysteine to serine substitutions also affect proteolytic susceptibility of bFGF during in vitro refolding from crude inclusion bodies. About 60% of human bFGF is lost to proteolytic degradation during in vitro refolding. Replacement of cysteines by serines increases the total recovery of bFGF, although more aggregates are formed during refolding. Ser-88-bFGF was expressed at the highest level, gave the highest soluble fraction in vivo, and exhibited the greatest fractional recovery and was recovered with the largest insoluble fraction after in vitro refolding. Thermal stability experiments at 42 degrees C and 70 degrees C revealed that cysteine to serine substitutions did not cause aggregation of the folded protein in vitro.

Base Sequence↗
PubMed1992

Toxoplasma pneumonitis: fatal presentation of disseminated toxoplasmosis in a patient with AIDS.

Toxoplasma gondii infection is an uncommon cause of pneumonitis in patients with acquired immune deficiency syndrome (AIDS). We report a case of fatal pulmonary toxoplasmosis, which clinically resembled Pneumocystis carinii pneumonia (PCP). Conventional diagnostic methods for toxoplasmosis lack sensitivity. Bronchoscopy and histological evaluation of transbronchial biopsy specimens failed to identify the infecting organism. At autopsy there was evidence of disseminated infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Caffeine restriction: effect on mild hypertension.

OBJECTIVE: To determine the effects on blood pressure of modifying dietary caffeine intake in patients with mild and borderline hypertension by monitoring ambulatory and clinic blood pressure. DESIGN: Four way, randomised, crossover trial of four consecutive two week dietary regimens: normal diet, caffeine free diet alone, caffeine free diet with decaffeinated instant coffee, caffeine free diet with caffeinated instant coffee (instant coffee phases conducted double blind). SETTING: Hospital hypertension clinic, Scotland. PATIENTS: 52 patients (23 men; aged 26-67 years) with untreated borderline or mild hypertension (diastolic blood pressure 90-105 mm Hg) who normally drank a minimum of three cups of coffee daily. MAIN OUTCOME MEASURES: Mean ambulatory blood pressure over 24 hours; mean morning, daytime, and night time ambulatory blood pressure; sitting clinic blood pressure at 1700; plasma caffeine concentration at 1700 on the last day of each regimen. RESULTS: Mean 24 hour ambulatory blood pressure was not different between regimens. There was no difference in blood pressure variability between regimens. During the caffeine free diet alone morning ambulatory diastolic blood pressure was higher (2.8 mm Hg) than during the caffeine free diet with caffeinated coffee. Mean sitting clinic systolic blood pressure was higher at 1700 (4.7 mm Hg) with a caffeine free diet than with the caffeine free diet with caffeinated coffee (p less than 0.05). Dietary compliance as assessed by plasma caffeine concentration was excellent. There was no significant correlation between plasma caffeine concentration and blood pressure. CONCLUSIONS: Drinking caffeinated instant coffee over a two week period does not adversely influence blood pressure in patients with borderline or mild hypertension; abstinence is of no benefit.

Adult↗
PubMed1988

Fast atom bombardment mass spectral search for the amino terminus of genetically engineered alpha 1-antitrypsin.

Protein structure determination of genetically engineered alpha 1-antitrypsin was carried out using the technique of 'fast atom bombardment (FAB) MAPPING'. CNBr, tryptic and chymotryptic FAB MAPS were produced. The anticipated amino terminal region of the molecule was not mapped at the expected mass, raising the possibility of post-translational modification. A specific experiment was designed to isolate and identify this region by FAB mass spectral screening of high-performance liquid chromatography separated peptides. A signal at m/z 1231 was observed which could not be assigned to any sequence in the molecule using the computer program. Following CNBr treatment, this signal disappeared completely, giving rise to a new signal at m/z 1058. The amino terminus was thus found to be extended by the presence of an N-acetyl methionine residue, and this discovery is the subject of the present paper; another modification within the sequence will be reported elsewhere. Combining the FAB MAPPING data, the overall structural confirmation achieved was 93% of the recombinant alpha 1-antitrypsin molecule.

Amino Acid Sequence↗
PubMed1987

Frontal sinus fractures. Analysis of treatment results.

A retrospective study of 112 consecutive patients with frontal sinus fractures who were available for follow-up is presented. Significant complications are possible, especially with fracture of the posterior sinus wall. When indicated, the sinus is reconstructed with wire using free denuded fragments if available. Severe complications in displaced posterior wall fractures were less common when treatment was by sinus obliteration than by cranialization. Computed tomography has improved the evaluation, especially when a posterior wall fracture is suspected.

Anti-Bacterial Agents↗
PubMed1987

Augmentation of lung antineutrophil elastase capacity with recombinant human alpha-1-antitrypsin.

To evaluate the potential use of recombinant DNA-produced alpha-1-antitrypsin (alpha-1-AT) to augment the lung antineutrophil elastase defenses in alpha-1-AT deficiency, we compared the kinetics of intravenously administered recombinant produced alpha-1-AT (r alpha-1-AT) and purified normal human plasma alpha-1-AT (p alpha-1-AT) in the blood and lung of rhesus monkeys. The r alpha-1-AT was produced in yeast transformed with an expressing plasmid containing a full-length human alpha-1-AT complementary deoxyribonucleic acid and purified to greater than 99% homogeneity. The r alpha-1-AT has a molecular weight of 45,000, no carbohydrates, and is identical in sequence to normal plasma alpha-1-AT except for an additional N-terminal acetylmethionine. Despite its lack of carbohydrates, the r alpha-1-AT inhibited human neutrophil elastase with an association rate constant similar to that of p alpha-1-AT. Rhesus monkeys were infused intravenously with 120 mg/kg of r alpha-1-AT (n = 13) or p alpha-1-AT (n = 12) and the serum, urine, and lung epithelial lining fluid (ELF) concentrations of these molecules quantified at various intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗