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Biomedical subjects

S R Williams

Publications and source records attributed to S R Williams.

At least 163 records · Page 9Linked to original sources
PubMed1988

A 31P nuclear magnetic resonance study in vivo of metabolic abnormalities in rats with acute liver failure.

31P NMR spectroscopy was used in conjunction with conventional biochemical techniques to study metabolic abnormalities in normal rats, in rats with CCl4-induced acute liver failure and in rats with paracetamol-induced acute liver failure. Studies were carried out before and after a metabolic challenge in the form of a fructose infusion. Prior to fructose infusion the ATP levels in the groups with acute liver failure were significantly lower than in control rats, despite their having a similar ATP/Pi ratio. Following a fructose infusion in control animals, the changes in phosphomonoesters, ATP and inorganic phosphate were consistent with previously reported findings. However, in both test groups the percentage changes in phosphomonoesters and ATP were significantly smaller. Intracellular pH declined in control animals, but did not change significantly in the animals with acute liver failure. Fructose clearance from the blood in control animals was not significantly different from that in animals with CCl4-induced acute liver failure. Metabolic changes measured using a horizontal magnet were very similar to those obtained with a vertical magnet.

Acetaminophen↗
PubMed1988

Does exposure of preovulatory oocytes to ultrasonic radiation affect reproductive performance?

Ultrasonography of preovulatory oocytes has been reported to lead to reduced litter size in rats. Because of the growing popularity of ultrasound-guided follicular aspiration in human in vitro fertilization programs, further study of ultrasonic radiation's effect on the preovulatory oocyte is warranted. We used 106 virgin Sprague-Dawley rats which, on the evening of proestrus, received ultrasonic radiation of sham treatment after the onset of the luteinizing hormone (LH) surge. No differences were found between control (C) and experimental (US) animals in pregnancy rate, number of corpora lutea, implantations, pups, and mean pup and placental weights at autopsy on day 22 of pregnancy. Ultrasonic radiation applied to meiotically active, preovulatory oocytes did not affect the reproductive performance of these rats.

Animals↗
PubMed1988

The role of the carbon dioxide laser in treatment of carcinoma of the tongue.

This paper presents 35 patients with carcinoma of the tongue who have been treated in Southampton using the Carbon Dioxide laser. The treatment programme for each individual patient was determined by radiotherapists and surgeons in a combined head and neck/oncology clinic. T1 carcinomas were treated by primary laser excision biopsy whereas larger tumours were treated first by conventional radiotherapy unless there was a significant contraindication to this treatment modality. Of 10 patients with T1 lesions nine are alive and well and disease free, but one patient died of other causes with no sign of recurrence. The minimum follow-up period has been two years. Of 25 patients with T2 and T3 lesions treated either before or after radiotherapy, nine are alive and disease-free, eleven died of disease and five patients died of other causes with no evidence of recurrence.

Carbon Dioxide↗
PubMed1988

Acute cerebral ischaemia: concurrent changes in cerebral blood flow, energy metabolites, pH, and lactate measured with hydrogen clearance and 31P and 1H nuclear magnetic resonance spectroscopy. III. Changes following ischaemia.

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anaesthesia. At the same time, intracellular pH and the concentrations of lactate and high-energy phosphates were measured in the brain using 1H and 31P nuclear magnetic resonance spectroscopy. Flow and metabolism have been followed during either a 15- or a 30-min ischaemic period (induced by bilateral carotid occlusion) and for up to 1 h of recovery. There was no significant difference between the flow characteristics of the two experimental groups. High-energy phosphate levels and pH returned to control within approximately 20 min of the end of the ischaemic period. Lactate clearance, following a 30-min occlusion, was slower than the recovery of pH. The concentration of free ADP, calculated from the creatine kinase equilibrium, was lower during the recovery phase than under control conditions.

Animals↗
PubMed1988

Three solutions for preservation of the rabbit heart at 0 degree C. A comparison with phosphorus-31 nuclear magnetic resonance spectroscopy.

Phosphorus-31 nuclear magnetic resonance has been used to measure changes in tissue adenosine triphosphate and pH that occur during hypothermic preservation of rabbit hearts. Three potential preservation solutions were studied: the St. Thomas' Hospital no. 1 cardioplegic solution, Bretschneider's HTP solution, and a solution originated in our laboratory, CP5, which we have previously studied in the rabbit heart with functional assessment by Langendorff perfusion. After being flushed with one of these solutions, each heart was stored at 0 degrees C for 12 hours, during which time it was subjected to repeated phosphorus-31 nuclear magnetic resonance scans. It was shown that adenosine triphosphate levels decayed more slowly with CP5 than with either of the other solutions or in the control experiments. Adenosine triphosphate decay was also slower with Bretschneider's HTP than with St. Thomas' Hospital solution, but pH was somewhat better maintained with Bretschneider's HTP than with either other solution or in the control hearts, although the pH did not decrease drastically in any group. CP5 was designed to prevent cell swelling and to reduce the uptake of calcium during storage, for which reasons it contains 30 mmol/L glucose and 0.1 mmol/L calcium. The potassium content is somewhat higher and the sodium and magnesium content somewhat lower than in St. Thomas' Hospital solution, with the objective of stabilizing intracellular concentrations of these ions during storage.

Adenosine Triphosphate↗
PubMed1988

Dose-dependent effects of postmenopausal estrogen and progestin on antithrombin III and factor XII.

The frequent use of estrogen and progestin replacement for treatment in postmenopausal women makes assessment of its effect on the coagulation system of interest. Although the amount of estrogen used to achieve the desired therapeutic effect is lower than the lowest doses in oral contraception, the age and medical condition of this population may amplify any hormone-induced risk. The common impression is that postmenopausal replacement therapy does not increase risk for thromboembolic disease, but no large epidemiologic studies of estrogen replacement have addressed that question. In this randomized prospective study, we examined the effects of varying low doses of an estrogen-progestin preparation on the titers of clotting factors in postmenopausal women. The coagulation factors selected for investigation were among those that have been reported to be significantly altered in the plasma samples of high-dose estrogen users. There were no changes in prothrombin time, factor X, fibrinogen, factor VII, or fibrinopeptide A in any of the hormone-treated groups. Mild but significant shortening of the partial thromboplastin time and elevation of factor XII titer were noted in all treatment groups. The titer of antithrombin III was reduced in the group given 20 micrograms ethinyl estradiol, but not in the groups given 5 or 10 micrograms. The clinical significance of these changes is difficult to determine in postmenopausal women receiving sex hormone replacement. However, we have not noted any thromboembolic episodes in our volunteers after a 1-year follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Biotransformation of aromatic compounds. Monitoring fluorinated analogues by NMR.

The results presented here illustrate the power of NMR in the non-invasive analysis of microbial transformations. Whilst the definitive identification of products requires purification and full structural elucidation. NMR can provide rapid insights into the nature of these reactions and their regulation in vivo. In addition, once the products have been identified NMR methods allow rapid assessment of the effects of genetic and physiological manipulation, and on competing metabolic fluxes with mixed substrates and branched pathways.

Benzene Derivatives↗
PubMed1987

A human purine nucleoside phosphorylase deficiency caused by a single base change.

Purine nucleoside phosphorylase (PNP) deficiency in humans is associated with a severe defect in T-lymphocyte function. The mutant gene was cloned from one PNP-deficient patient who was the offspring of a consanguineous mating. The exons and intron/exon boundaries of the mutant PNP gene were sequenced and compared with the wild-type cDNA sequence. A single base difference was found in the coding region of the mutant gene, a G to A transition in the third exon. This single base mutation alters the codon at position 89 from Glu to Lys, a result which is consistent with previously published peptide mapping data. The patient was demonstrated to be autozygous for the single base mutation on the basis of hybridization of synthetic oligomers to genomic DNA digests. A mammalian expression vector was constructed containing the entire mutant gene under the transcriptional regulation of its own promoter. In another construction, the single base mutation was reverted to the wild-type sequence by in vitro mutagenesis. An isoelectric focusing gel containing extracts of the cells transfected with the mutant and reverted PNP gene was stained histochemically for PNP activity. The proteins from a similar gel were blotted on a nitrocellulose membrane, and immunoreactive human PNP protein was visualized. Cells transfected with the mutant gene contained no human PNP activity, but expressed immunoreactive PNP which focused at an abnormally alkaline pI. Cells transfected with the reverted gene expressed human PNP activity which co-focused with human PNP from a HeLa cell control, proving that the observed single base change was responsible for the loss of catalytic function.

Amino Acid Sequence↗
PubMed1987

Spectral resolution in clinical magnetic resonance spectroscopy.

We observe linewidths of 0.1-0.4 ppm in 31P spectra of human muscle, liver, and brain. T2 measurements of muscle phosphocreatine, together with previous brain studies, indicate that further improvements in linewidth to 0.02-0.05 ppm might often be achieved, but in some lesions magnetic susceptibility variations may limit spectral resolution.

Brain↗
PubMed1987

Acute cerebral ischaemia: concurrent changes in cerebral blood flow, energy metabolites, pH, and lactate measured with hydrogen clearance and 31P and 1H nuclear magnetic resonance spectroscopy. I. Methodology.

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anaesthesia. This has been correlated with changes in local pH, tissue lactate, and phosphorus energy metabolites measured in the same animals with 1H and 31P nuclear magnetic resonance (NMR) spectroscopy. The NMR measurements were made with two surface coils, one on each hemisphere. This article describes the experimental details and shows that in acute unilateral or bilateral forebrain ischaemia metabolic changes can be monitored by NMR with no significant interhemispheric cross talk. The metabolic effects of reperfusion are also shown. The model allows the definition of the time course of the metabolic consequences of regional ischaemia and reperfusion in individual laboratory animals.

Acute Disease↗
PubMed1987

Acute cerebral ischaemia: concurrent changes in cerebral blood flow, energy metabolites, pH, and lactate measured with hydrogen clearance and 31P and 1H nuclear magnetic resonance spectroscopy. II. Changes during ischaemia.

CBF has been measured with the hydrogen clearance technique in the two cerebral hemispheres of the gerbil under halothane anesthesia. This has been correlated with changes in local pH, tissue lactate, and phosphorus energy metabolites measured in the same animals with 1H and 31P nuclear magnetic resonance spectroscopy. We demonstrate a threshold flow value for the metabolic changes associated with energy failure at a level similar to the values previously reported for electrical failure and tissue water accumulation, but higher than that associated with breakdown of extracellular potassium homeostasis.

Animals↗
PubMed1987

Human purine nucleoside phosphorylase and adenosine deaminase: gene transfer into cultured cells and murine hematopoietic stem cells by using recombinant amphotropic retroviruses.

Cell lines were established which produced high titers (approximately 10(6) infectious units per ml) of amphotropic, replication-defective recombinant retroviruses which transduced sequences encoding either human purine nucleoside phosphorylase (PNP) or adenosine deaminase (ADA). These viruses also contained a human hypoxanthine phosphoribosyltransferase gene as a selectable marker and a mouse metallothionein promoter (MMP) sequence just upstream from the PNP or ADA genes. Virus structure was maintained through the replication cycle if a short (216-base pair) MMP sequence was used. However, the use of a longer (1,834-base pair) MMP sequence resulted in the deletion of a significant portion of the recombinant virus genome, including the transcriptional regulatory elements of the MMP sequence. Northern analysis indicated a predominance of genome length transcripts in cells infected with deleted virus. The demonstration of substantial human PNP or ADA activity in virus-infected mouse fibroblasts by isozyme analysis suggested that active gene product was translated from either spliced or bicistronic message. The deleted ADA and PNP viruses were introduced into mouse hematopoietic stem cells by cocultivating freshly explanted bone marrow with virus producer cells. The infected marrow cells were injected into irradiated, syngeneic recipient mice, and the presence of integrated ADA or PNP proviral sequences was demonstrated in the DNA of spleen colonies by Southern analysis. Failure of these integrated proviral sequences to express active, human isozyme in spleen colony tissue indicated the existence of some regulatory constraint not active in cultured mouse cells.

Adenosine Deaminase↗
PubMed1987

Intracellular metabolites in rat muscle following trauma: a 31P and 1H nuclear magnetic resonance study.

Hind limb skeletal muscle was studied in vivo in a rat trauma model using nuclear magnetic resonance (NMR) spectroscopy. The model used was a 25% body surface area, full-thickness burn administered under anaesthesia. Two groups of six rats were studied. Weight loss was observed in the experimental group whilst the control group continued to gain weight. Concentration ratios involving intramyocellular phosphocreatine (PCr), creatine (Cr), adenosine triphosphate (ATP), inorganic phosphate (Pi), anserine (Ans) and taurine (Tau) were measured. No change in the ratios of PCr/Pi, PCr/ATP, Ans/PCr + Cr and Tau/PCr + Cr were seen between the two groups. Intracellular pH was the same in the two groups. NMR spectroscopy in vivo gives values of Pi and PCr that differ from those obtained by conventional techniques. NMR values are probably more accurate as no degradation occurs during measurement, the measurements being repeatable and noninvasive.

Adenosine Triphosphate↗
PubMed1986

Spin-echo and 2-dimensional 1H nuclear magnetic resonance studies on urinary metabolites from patients with 2-methylacetoacetyl CoA thiolase deficiency.

Spin-echo 1H nuclear magnetic resonance (nmr) spectra of urine from two unrelated patients with 3-oxoacylthiolase deficiency are presented. The metabolite profile revealed by these spectra is probably of diagnostic value. Two of the major abnormal metabolites known to accumulate in this disorder (tiglylglycine and 2-methyl-3-hydroxybutyrate) can both be detected in the spectra. The technique offers the advantage over combined gas chromatography/mass spectrometry that no pre-treatment of the sample is required and that the data can be obtained in less than 2 min. In addition 2-dimensional nmr techniques (J-resolved and chemical shift correlated) were used to further characterise the spectra. This allowed assignment of resonances which could not be detected in the spin-echo spectra, in particular 2-methylacetoacetate and butanone, which are known to accumulate in this disease.

Acetyl-CoA C-Acyltransferase↗
PubMed1986

3-Hydroxy-3-methylglutaryl-CoA lyase deficiency studied using 2-dimensional proton nuclear magnetic resonance spectroscopy.

1H-NMR spectroscopy has been applied to identify components in the urine of subjects with a deficiency of the enzyme 3-hydroxy-3-methylglutaryl-CoA lyase. One-dimensional spectra of samples from a pair of non-identical twins with this disorder were very similar and are probably diagnostic. The most intense signals were from singlets. Complete assignment of these major components was made possible by the use of 2-dimensional chemical shift correlated spectroscopy since several long-range couplings were detected. 2-dimensional spectroscopic techniques may therefore be of value in the identification of singlets in multicomponent systems.

Amino Acid Metabolism, Inborn Errors↗