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Biomedical subjects

M A Foster

Publications and source records attributed to M A Foster.

At least 73 records · Page 4Linked to original sources

Changes in NMR relaxation time associated with local inflammatory response.

T1 and T2 relaxation values and water contents of rat and rabbit tissues have been measured during the course of local inflammatory reaction to turpentine. For rabbits, NMR transverse sectional images were also obtained by spin-warp imaging. Elevations in T1 values around the injection site occurred within 24 h. In rats, T1 values of fibrosed muscle at the centre of the reaction continued to rise as a cyst formed, encapsulating the turpentine. T1 values of the surrounding muscle decreased towards normal as the reaction progressed. Good correlation between relaxation rate and water content was observed. In the rabbits. T1 values measured in vitro around the injection site were compared with the values obtained from NMR images of living and dead rabbits, T1 values obtained immediately after death were consistently lower than values of the same tissues before death. Factors affecting a comparison of T1 values obtained by the different methods are discussed.

Animals↗

Glycerol fermentation in Klebsiella pneumoniae: functions of the coenzyme B12-dependent glycerol and diol dehydratases.

Glycerol and diol dehydratases are inducible, coenzyme B12-dependent enzymes found together in Klebsiella pneumoniae ATCC 25955 during anaerobic growth on glycerol. Mutants of this strain isolated by a novel procedure were separately constitutive for either dehydratase, showing the structural genes for the two enzymes to be under independent control in vivo. Glycerol dehydratase and a trimethylene glycol dehydrogenase were implicated as members of a pleiotropic control system that includes glycerol dehydrogenase and dihydroxyacetone kinase for the anaerobic dissimilation of glycerol (the "dha system"). The dehydratase and dehydrogenases were induced by dihydroxyacetone and were jointly constitutive in mutants isolated as constitutive for either the dha system or glycerol dehydratase. These data and the stimulation of growth by Co2+ suggested that glycerol dehydratase and trimethylene glycol dehydrogenase are obligatory enzymes for anaerobic growth on glycerol as the sole carbon source.

Alcohol Oxidoreductases↗

In vivo n.m.r. imaging in medicine: the Aberdeen approach, both physical and biological.

A novel magnetic field and radio frequency (1.7 MHz) pulse sequence is described for a whole body n.m.r. imaging machine under construction. Selective excitation is used to obtain signals from successive lines of proton spins(water) across the body to build up an image of a transverse section. The images display spin concentration and spin-lattice relaxation time, T1, separately. For a 50% change in T1 to be discerned in the human trunk, a spatial resolution of 2 cm3 is expected for a 2 min scan and 0.5 cm3 for a 30 min scan. Very preliminary images at the present incomplete stage of development show the geometrical accuracy and T1 discrimination: an in vivo image demonstrates some of the difficulties to be overcome. In vitro measurements of normal rabbit tissue samples have been made at 24 MHz to map the T1 distributions that can be expected from normal subjects. The transposition of this information from rabbit to man, and from 24 MHz to 2.5 MHz have been checked and the comparison shown to be meaningful. Of pathological samples, human breast tumour and human liver metastases offer a good contrast to their surrounding tissue, and an experimental investigation has shown that tissue immediately surrounding a tumour also has an elevated T1 value. A wide range of abnormalities that are associated with abnormal fluid formation in the body may be amenable to imaging by the n.m.r. technique. Potential hazards are believed to be small in the present generation of equipment.

Animals↗

A preliminary investigation of 67Ga citrate distribution in hyperferraemic patients.

Scanning for malignant or inflammatory lesions with 67Ga citrate currently has a number of major limitations. In an effort to improve visualisation of the abdomen and pelvis, and to reduce the time between 67Ga citrate injection and the scan (usually 72 h) a series of patients was given an intramuscular injection of 100 mg iron-sorbitol citric acid complex (jectofer) two hours prior to receiving an intravenous injection of 67Ga citrate. Laboratory measurements on blood samples removed at different times showed that this pre-treatment altered radically both the amount of free transferrin and the level of 67Ga activity in the blood pool for the majority of patients. Follow up of 30 patients entered in this preliminary trial showed that when 24 h and 48 h scans were analysed together, accuracy in the diagnosis and localisation of pathological lesions was at least as good as by the standard method. We believe that by saturating the free transferrin with iron, uptake into normal soft tissues may be modified sufficiently to enhance significantly the tumour to background ratio, thereby making earlier scanning possible. Investigations are continuing.

Citrates↗

DAB-induced changes in NMR relaxation times, water and iron content of rat tissue.

T1 relaxation values of rat liver and spleen tissue have been measured over a 6-month period whilst feeding with p-dimethyl-aminoazobenzene (DAB). Measurements of tissue water and iron content have also been made. A small rise in liver T1 value during the early stages of DAB feeding, from a control value of 296 +/- 12 ms to 318 +/- 12 ms after 3 weeks, probably reflected toxic reaction to the diet rather than preneoplastic changes. Spleen T1 value showed a considerable decrease over this same period, from a mean control value of 505 +/- 14 ms to 394 +/- 21 ms after 3 weeks on the diet. The possible origins of this change are discussed.

Animals↗

Resolution of the coenzyme B-12-dependent dehydratases of Klebsiella sp. and Citrobacter freundii.

Diol dehydratase (1,2-propanediol hydro-lyase, EC 4.2.1.28) and glycerol dehydratase (glycerol hydro-lyase, EC 4.2.1.30) are shown to be distinct, separable enzymes that occur individually or together in different strains of Klebsiella sp. Anaerobic growth with propan-1,2-diol induces diol dehydratase alone, whereas glycerol fermentation induces both enzymes in K. pneumoniae ATCC 25955 and in Citrobacter freundii NCIB 3735. The dehydratases can be resolved by polyacrylamide-gel electrophoresis or separated by anion-exchange chromatography alone. Sucrose density gradient centrifugation failed to distinguish the enzymes and indicated a molecular weight of 1.9 . 10(5) for both. The enzymes can be assayed individually, even when present in the same crude extract, using the 67-fold difference in their Km values for coenzyme B-12. For both enzymes inactivation kinetics are observed with glycerol as substrated, and monovalent cations influence both the inactivation rate and catalytic rate of the reaction.

Chromatography, Ion Exchange↗

Changes in NMR relaxation times of adjacent muscle after implantation of malignant and normal tissue.

In separate experiments, normal foreign tissue and malignant tumour were implanted s.c. into the rat thigh. NMR T1 values of the adjacent normal muscle, resulting from local inflammatory reactions or from malignant invasion, were measured. Elevations in T1 of the underlying muscle occurred within 24 h in both experiments, and it is believed these were caused by rapid inflammatory and immunological reactions to the implants. However the T1 values of muscle samples adjacent to the non-malignant implants decreased during the 11 days after implantation, dropping to values within the normal range. In the second experiment there was progressive malignant invasion into the normal adjacent tissue and the elevated T1 values were maintained throughout the 12-day period. The effects of the implantation on tissue water content are discussed in relation to NMR T1 relaxation times, and the relevance to whole-body NMR imaging of elevated T1 values due to nonmalignant pathological states is considered.

Animals↗

Electron spin resonance of caeruloplasmin and iron transferrin in blood of patients with various malignant diseases.

Electron spin resonance studies have been made of caeruloplasmin and iron transferrin levels in whole blood of healthy controls and patients with a variety of malignant conditions receiving various forms of treatment. A small difference was found in caeruloplasmin level between normal males and females, although normal females receiving contraceptive steroids had an elevated level. No difference was found in iron transferrin level. Various conditions increased the caeruloplasmin and some also decreased the iron transferrin level in patients with malignant disease. These included surgery and the approach of a terminal phase of disease. Once allowance for these factors was made, the remaining small differences in Cu and Fe between patients with either squamous cell carcinoma or breast cancer and controls appeared to have no clinical significance.

Adolescent↗