PubMed Health⌕ Search

Biomedical subjects

J R Griffiths

Publications and source records attributed to J R Griffiths.

At least 19 recordsLinked to original sources
PubMed1992

An investigation of tumor 1H nuclear magnetic resonance spectra by the application of chemometric techniques.

1H nuclear magnetic resonance (NMR) spectra of tumors and normal tissue include signals from all hydrogen-containing metabolites and can therefore be considered multicomponent multivariate mixtures. We have obtained 1H spectra from perchloric acid extracts of three normal tissues (liver, kidney, and spleen) and five rat tumors (GH3 prolactinoma, Morris hepatomas 7777 and 9618a, LBDS1 fibrosarcoma, and Walker 256 carcinosarcoma). We have applied several different chemometric methods to analyze the data. First, we used principal component analysis, cluster analysis, and an optimized artificial neural network to develop a classification rule from a training set of samples of known origin or class. The classification rule was then assessed using a set of unknown samples. We were able to successfully determine the class of each unknown sample. Second, we used the chemometric techniques of factor analysis followed by target testing to investigate the underlying biochemical differences that are detected between the classes of samples.

Adenocarcinoma↗
PubMed1992

Magnetic resonance neurography.

We have made cross-sectional image "neurograms" in which peripheral nerve has a greater signal intensity than that of other tissue. Neurographic images of the rabbit forelimb were obtained using a spin-echo magnetic resonance imaging (MRI) technique that combines fat suppression and diffusion weighting. After fat suppression the nerve shows up in relative isolation and is brighter than the surrounding tissue due to its longer T2 relaxation time of approximately 50 ms compared to approximately 27 ms for muscle. The addition of pulsed gradients for diffusion weighting of the MR signal further enhances the intensity of the nerve signal relative to that of surrounding muscle tissue. The greater diffusional anisotropy of nerve tissue (D parallel/D perpendicular = 3.1) compared to that of muscle (D parallel/D perpendicular = 1.9) allows further enhancement of the nerve by a subtraction of two diffusion-weighted images, one with the gradients oriented parallel and one with the gradients oriented perpendicular to the nerve orientation. We show that by manipulation of the MRI parameters, either echo time or pulsed gradient strength, the nerves can be made to show up as the most intense feature. This verifies the feasibility of generating three-dimensional "neurographic" images, analogous to angiograms, but which demonstrate the peripheral nerve tracts in apparent isolation.

Adipose Tissue↗
PubMed1992

A two-compartment phosphate-doped gel phantom for localized spectroscopy.

Acrylamide gel loaded with phosphate has been used in two compartment phantoms designed to assess localized spectroscopy techniques. A chemical shift difference of 2.3 ppm was produced by changing the pH from 6 to 8.9. The 31P relaxation times were modified by doping the gels with paramagnetic ions. For a T1 of approximately 1 sec nickel doping gave a T2 of approximately 110 msec and manganese doping gave a T2 of approximately 8 msec. Gel phantoms are more robust than their liquid equivalent and are not prone to leakage. The construction of small compartments with very thin walls is possible, making this type of phantom suitable for small bore imaging/spectroscopy systems.

Acrylic Resins↗
PubMed1992

Enhanced 5-fluorouracil cytotoxicity and elevated 5-fluoronucleotides in the rat Walker carcinosarcoma following methotrexate pre-treatment: a 19F-MRS study in vivo.

5-fluorouracil (5FU) is activated intracellularly to cytotoxic 5-fluoronucleotides (FNuct). These were detected non-invasively in rats bearing the Walker carcinosarcoma by 19F-magnetic resonance spectroscopy (MRS) following an i.v. bolus dose of 5FU (50 mg kg-1). Pre-treatment of the rats (3 to 24 h earlier) by methotrexate (MTX) (20 or 50 mg kg-1) did not affect the rate of 5FU disappearance but did significantly increase the rate of FNuct formation (P less than 0.002) and the final amount formed (P less than 0.02) as assessed by MRS in vivo. MTX (20 mg kg-1) caused substantially the same effects on FNuct formation (P less than 0.002 for rate and P less than 0.05 for the amount) when 5FU was administered i.p. although higher doses of 5FU (120 mg kg-1) were necessary to observe the 19F-signals. Quantitative analysis by MRS in vitro of extracts from the freeze-clamped tumours treated by 5FU i.v. confirmed that MTX pre-treatment increased FNuct formation 3-fold (P less than 0.05). Hplc quantitative analysis demonstrated that 50% of the FNuct was the cytotoxic nucleotide FUTP which was also increased 3-fold in MTX treated animals (P less than 0.05). Since the Walker tumour is probably sensitive to 5FU action via FUTP incorporation into RNA, these results suggested that drug regimes in which MTX preceded 5FU (MTX-5FU schedule) would be more cytotoxic that 5FU alone. At an MTX dose of 20 mg kg-1 24 h prior to 5FU there was significant inhibition of growth (P less than 0.05) compared to no treatment, MTX alone or the reverse schedule of 5FU-MTX. These results suggest MRS may be of clinical value in optimising chemotherapy using schedules where MTX precedes 5FU.

Animals↗
PubMed1992

Proceedings of a National Cancer Institute workshop: MR spectroscopy and tumor cell biology.

In December 1991, the National Cancer Institute held a workshop to evaluate the role of magnetic resonance (MR) spectroscopy in human cancer biology. The clinical and basic cancer research issues requiring use of MR spectroscopy, the advantages and limitations of MR spectroscopy, and future directions in MR spectroscopy of cancer were discussed. Consensus-building panels were formed on the following four topics: cell membrane biochemistry, tumor therapeutic response or drug resistance, appropriate model systems, and potential clinical applications of MR spectroscopy. The workshop members concluded that large prospective clinical studies as well as in vivo animal and human studies to define prognostic variables should be performed, with correlation between MR spectroscopic results and biochemical and physiologic features. Studies of phospholipid metabolism, the pharmacokinetics of anticancer agents, and effects of new cancer treatments on the tumor vasculature and normal tissues are needed.

Humans↗
PubMed1991

Detection of differential sensitivity to 5-fluorouracil in Ehrlich ascites tumour cells by 19F NMR spectroscopy.

Quantitative analysis of extracts from two Ehrlich ascites tumour cell lines (Lettre cells) by 19F NMR in vitro demonstrated that one Lettre cell line (designated LLM) metabolized 30-50% less 5-fluorouracil to 5-fluoronucleotides when compared to the other cell line (designated LHM). HPLC analysis of these cellular extracts showed a significant decrease in the concentration of the cytotoxic nucleotide 5-fluorouridine triphosphate in LLM cells compared to LHM cells. No major differences could be observed in the 31P and 1H NMR spectra of the two cell lines. Growth inhibition studies in vitro demonstrated that LLM cells were less sensitive to 5-fluorouracil than LHM cells. These results are consistent with the hypothesis that 19F NMR visible levels of 5-fluoronucleotides can predict the cytotoxicity of the anti-cancer drug 5-fluorouracil.

Adenosine Diphosphate↗
PubMed1991

Differences in vascular response between primary and transplanted tumours.

The vast majority of studies on tumour vasculature are performed on transplanted tumours in rodents. However, it is known that there may be differences between primary and transplanted lesions. The purpose of this study is to test whether a specific vascular response is similar in primary tumours and in transplanted tumours derived from them. The technique used was to give an intraperitoneal injection of 5 mg kg-1 hydralazine, which is known to result in hypoxia in transplanted tumours. Changes in perfusion were indicated by changes in metabolism, monitored using 31P Magnetic Resonance Spectroscopy. The primary tumours were induced by local irradiation many months previously and only 4/11 (36%) of these responded to hydralazine. One of the non responders was subsequently transplanted into isogeneic mice to produce a tumour line which was histologically very similar to the primary. Of these 16/17 (94%) responded. The difference is statistically significant (P = 0.001). The reasons for this difference are not known. A number of possibilities are discussed and in the authors' opinion, the most likely cause is that it results from an artefact of transplantation.

Animals↗
PubMed1979

Activation of AMP aminohydrolase during skeletal-muscle contraction.

AMP aminohydrolase activity is enhanced by 60% after 5 s tetanic stimulation of phosphorylase kinase-deficient mouse muscle and after 60 s tetanus in normal mice. During the recovery from tetanus the activity in the contralateral leg is similarly enhanced. The activation is stable to 1000-fold dilution and has a half-life of approx. 1 h.

AMP Deaminase↗
PubMed1977

Renal function after warm ischaemia. II. Marked protective effect of intravenous inosine given prior to 60, 90 and 120 min of warm ischaemia.

Rats were given 10 or 20 mg of inosine dissolved in 1 ml of 0.9% saline, or a control solution of 1 ml of 0.9% saline, intravenously 10 or 20 min before induction of left renal warm ischemia for 60 min. Further groups of rats were treated with 20 mg inosine or with saline alone 20 min before longer periods of warm ischeamia of 90 and 120 min duration. All animals had immediate contralateral nephrectomy. In all inosine-treated groups the mean plasma creatinine was lower than in their respective control groups and these differences were statistically highly significant.

Animals↗