Search PubMed⌕ Search

Biomedical subjects

J D Bell

Publications and source records attributed to J D Bell.

At least 73 records · Page 4Linked to original sources

Changes in adipose tissue composition in malnourished patients before and after liver transplantation: a carbon-13 magnetic resonance spectroscopy and gas-liquid chromatography study.

We investigated adipose tissue fatty acid composition in 22 moderately to severely malnourished patients with cirrhosis and in 22 healthy volunteers by in vivo carbon-13 magnetic resonance spectroscopy (MRS). Gas-liquid chromatography (GLC) of adipose tissue samples was also performed in 11 of the patients and in 4 volunteers. In vivo 13C magnetic resonance spectra were obtained from the subcutaneous adipose tissue before and after eight weeks following orthotopic liver transplantation (OLT). Adipose tissue biopsy samples were obtained for GLC analysis at the time of transplantation in the patients and at inguinal hernia repair in the 4 volunteers. No significant differences were found in the subcutaneous adipose tissue total-saturated, -polyunsaturated or -monounsaturated fatty acid composition between patients and healthy volunteers by in vivo 13C MRS. GLC analysis of adipose tissue samples confirmed that total levels of saturated, poly-, and monounsaturated fatty acids remained the same but revealed significant differences in levels of individual fatty acids, particularly n-3 fatty acids (total n-3, cirrhotics: .84% +/- .07% vs. controls: 1.36% +/- .13%, P < .01). Eight weeks following transplantation, recipients showed a considerable increase in body mass (pretransplantation: 59.3 +/- 3.2 vs. posttransplantation: 63.2 +/- 3 kg, P < .01). 13C MRS revealed a significant increase in saturated fatty acids (pretransplantation: 21.6 +/- 2.8 vs. posttransplantation: 25.5% +/- 1.2%, P < .05) and a significant decrease in unsaturated fatty acids. The application of noninvasive MRS techniques may be important to identify the differential uptake of fats, examining both specific fatty acids and different body fat compartments. In the future, this may be useful in optimizing the dietary management of severely malnourished patients with chronic liver disease before liver transplantation.

Adipose Tissue↗

Assessment of quantitative artificial neural network analysis in a metabolically dynamic ex vivo 31P NMR pig liver study.

Quantitative artificial neural network analysis for 1550 ex vivo 31P nuclear magnetic resonance spectra from hypothermically reperfused pig livers was assessed. These spectra show wide ranges of metabolite concentrations and have been analyzed using metabolite prior knowledge based lineshape fitting analysis which had proved robust in its biochemical interpretation. This finding provided a good opportunity to assess the performance of artificial neural network analysis in a biochemically complex situation. The results showed high correlations (0.865 < or = R < or = 0.992) between the lineshape fitting and artificial neural network analysis for the metabolite values, and the artificial neural network analysis was able to fully represent the trends in the metabolic fluctuations during the experiments.

Animals↗

Noninvasive characterization of neonatal adipose tissue by 13C magnetic resonance spectroscopy.

In vivo 13C magnetic resonance spectroscopy (MRS) was applied noninvasively to analyze the fatty acid composition of adipose tissue in 21 full-term newborn infants and 6 mothers. In order to assess the effects of gestational and postnatal age on adipose tissue composition, we studied preterm infants at birth, term infants at the ages of 6 wk and at 6 mon. We also investigated the influence of maternal diet on infant adipose tissue composition by studying the breast-fed infants of women who maintained either an omnivore or a vegan diet. Significant differences were observed in adipose tissue composition of neonates compared with their mothers. Neonates had more saturated and less unsaturated fatty acids than their mothers (P < 0.01). We also observed changes in adipose tissue composition with maturity. From birth to 6 wk of age 13C MR spectra showed a significant increase in the amount of unsaturated fatty acids, particularly polyunsaturated fatty acids (P < 0.01). Similarly, differences were seen as a result of gestational age. Preterm infants had relatively fewer unsaturated fatty acids than full-term infants. A greater proportion of these unsaturated fatty acids were polyunsaturated. Our results demonstrate that 13C MRS can be utilized to assess noninvasively neonatal adipose tissue lipid composition and to monitor the effects of developmental changes due to gestational age and oral feeding.

Adipose Tissue↗

Non-invasive assessment of ATP regeneration potential of the preserved donor liver. A 31P MRS study in pig liver.

We have developed a quick, non-invasive method for measuring the ability of an isolated preserved liver to regenerate high energy phosphate nucleotides without the need for biopsy. Using 31P MRS we have monitored the hepatic energetics of intact cold preserved pig liver using standard clinical harvesting and storage techniques. Following cold storage for 2 h the livers were hypothermically reperfused with oxygenated modified University of Wisconsin preservation fluid. Prior to reperfusion MRS detectable adenosine diphosphate plus adenosine triphosphate was negligible; however, the spectrum showed intense resonances from phosphomonoesters and inorganic phosphate, as a consequence of adenosine triphosphate hydrolysis during cold preservation. Following a 10-min period of hypothermic reperfusion, regeneration of adenosine triphosphate occurred with a concurrent decline in inorganic phosphate and phosphomonoester, both of which are associated with adenosine triphosphate synthesis. The capacity of the liver to regenerate adenosine triphosphate following a 24-h period of cold storage was reduced by approximately 40% (p < 0.01) of the total amount achieved following the shorter cold storage time. Adenosine triphosphate regeneration rates were biphasic and were decreased upon prolonged storage, with the initial rate being reduced from 40.6 x 10(-2).min-1 (standard deviation (sd) 2.70 x 10(-2).min-1) to 14.8 x 10(-2).min-1 (sd; 2.4 x 10(-2).min-1) and the secondary rate from 1.77 x 10(-2).min-1 (sd; 0.18 x 10(-2).min-1) to 0.84 x 10(-2).min-1 (sd; 0.45 x 10(-2).min-1). MR images of the liver during the period of hypothermic reperfusion were also performed providing an assessment for the degree of hepatic vascular perfusion. This non-invasive, 31P MRS assessment of hepatic energetics in a clinically relevant animal model has great potential for the understanding of graft preservation injury.

Adenosine Diphosphate↗

Veterinary practice, competition and advertising: 1985-1994.

In 1985, members of the veterinary profession and four other professional groups in New Zealand were surveyed to establish their attitudes towards the developing commercialisation of their professions, and particularly towards advertising. This survey was repeated in 1988, and again in 1994. The results of the three surveys are presented in this paper. There was a sharp movement towards acceptance of advertising, and toward a competitive orientation in general, between 1985 and 1988, with a consolidation of these changes during the following 6 years. The acceptance of the idea of an openly competitive profession now has widespread support among veterinarians. Similarly, there is general support for the use of most kinds of informative advertising, with many practitioners viewing advertising as a business building tool, but with the advertising of fees remaining an area over which there is still considerable caution. Although clients are seen as more demanding than in the past, the client-practitioner relationship is still expected to be an enduring one. We suggest that, in view of the relaxed attitudes towards advertising that now exists among members of the veterinary profession, control of advertising should cease to be a concern to the profession.

Journal Article↗

A binding study of phospholipase A2 with lecithin, lysolecithin and their tetrahedral intermediates using molecular modeling.

We used molecular modeling to examine the binding of 1,2-dioctanoyl-sn-glycero-3-phosphocholine (a lecithin), 1-octanoyl-sn-glycero-3-phosphocholine (a lysolecithin) and their tetrahedral intermediates in the catalytic site of phospholipase A2 (PLA2). We performed energy minimization on each complex, computed the binding energy, determined the relative binding energy among the complexes and calculated the difference in inter- and intramolecular energies of the components in the complexes. We found that the calculated orientation of the sn-1 ester bond of lysolecithin in the active site is similar to that of the sn-2 ester bond in lecithin, thus permitting PLA2 to hydrolyze lysolecithin using the same mechanism as it uses to hydrolyze lecithin. On the other hand, the binding of lecithin is energetically more favorable by 4.5 kcal/mol than the binding of lysolecithin to the enzyme, and the binding of the lecithin tetrahedral intermediate is also energetically more favorable by 19.7 kcal/mol than the binding of the lysolecithin tetrahedral intermediate to the enzyme, which explains why lecithin is a better substrate than lysolecithin in the catalytic site. These results indicate that the activation energy for the hydrolysis of lysolecithin is higher than that for lecithin, consistent with the observed slower rate for the hydrolysis of lysolecithin.

Animals↗

In vivo and in vitro hepatic 31P magnetic resonance spectroscopy and electron microscopy of the cirrhotic liver.

In vivo 31P magnetic resonance spectroscopy (MRS) provides direct biochemical information on hepatic metabolic processes. To assess in vivo changes in hepatic 31P MRS in liver transplant candidates, we studied 31 patients with cirrhosis of varying aetiology; 14 with compensated cirrhosis (Pugh's score < or = 7) and 17 with decompensated cirrhosis (Pugh's score > or = 8). Underlying cellular abnormalities were characterised using in vitro 31P MRS and electron microscopy. In vitro spectra were obtained from liver extracts, freeze-clamped at recipient hepatectomy, from all subjects. Electron microscopy of liver tissue was also performed in 17 cases. Relative to nucleotide triphosphates, elevations in phosphomonoesters and reductions in phosphodiesters were observed in vivo with worsening liver function. In vitro spectra showed elevated phosphoethanolamine and phosphocholine, and reduced glycerophosphorylethanolamine and glycerophosphorylcholine, mirroring the in vivo changes, but no distinction was noted between compensated and decompensated cirrhosis. With electron microscopy, functional decompensation was associated with reduced endoplasmic reticulum in parenchymal liver disease, but elevated levels in biliary cirrhosis. We conclude that in vivo spectral abnormalities in cirrhosis are consistent with alterations in phospholipid metabolism and quantity of endoplasmic reticulum. However, in individual patients the biopsy results do not always mirror in vivo findings.

Adult↗

The application of NMR spectroscopy to the study of apoptosis.

Programmed cell death is a physiological process whereby multicellular organisms eliminate unwanted cells. The unravelling of this process has thus far remained in the hands of molecular and cell biologists. These studies have therefore led to a detailed understanding of the genetic nature and some control mechanisms regulating this complex process. However, the biochemical consequences of apoptosis within the cell still remain elusive. NMR spectroscopy, which allows the detection, identification and quantitation of a large number of metabolites and macromolecules, is being utilized to define some of these metabolic processes. The initial application of NMR spectroscopy, to solving the mysteries of apoptosis were confined to elucidating the macromolecular structure of the proteins involved in initiating programmed cell death. The ability of NMR to monitor energy metabolites non-invasively was so put to use in correlating the temporal changes in the rate of apoptosis to these metabolites. More recent studies have shown changes in both a range of small molecules and membrane components. The power of NMR spectroscopy is being used in more laboratories and is likely to become the method of choice for the possible detection of apoptosis in vivo once the NMR signals associated with the apoptotic process have been established in vitro.

Animals↗

Hepatic nucleotide triphosphate regeneration after hypothermic reperfusion in the pig model: an in vitro P-NMR study.

The aim of this study was to assess the possibility of regenerating nucleotide triphosphates (NTP) in the pig liver following its harvest and subsequent storage on ice. This study has used a pig model that allowed human donor liver retrieval techniques and methods of storage to be utilized. In vitro phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to evaluate the changes associated with phosphorus containing metabolites such as NTP, phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Po). During 4 hr storage NTP levels were reduced to undetectable levels but its regeneration was possible over a period of 2 hr of oxygenated hypothermic reperfusion. Resynthesized NTP reached values that were only 30% reduced from pre-harvest values. There was a corresponding reduction in Pi over the same period. Glycolytic intermediates, 3-phosphoglycerate and 2,3 diphosphoglycerate, both increased significantly during the period of storage and subsequently declined following hypothermic reperfusion. Cellular damage, indicated by the concentrations of glycerophosphorylcholine (GPC) and glycerophosphorylethanolamine (GPE) was minimal during cold storage. However upon hypothermic reperfusion, concentrations of GPC and GPE reduced, indicating a degree of cellular damage caused by reperfusion. This study has shown for the first time that is possible to regenerate high energy phosphate nucleotides following a period of hypothermic reperfusion in a large, clinically related animal model. This technique warrants investigation clinically to improve the outcome of orthotopic liver transplantation. It also provides a method to study the effects of different preservation fluids and methods of storage and organ reperfusion.

2,3-Diphosphoglycerate↗

Characterisation of secondary metabolites associated with neutrophil apoptosis.

We studied changes in secondary metabolites in human neutrophils undergoing constitutive or tumour necrosis factor (TNFalpha) stimulated apoptosis by a combination of high-performance liquid chromatography (HPLC) and NMR spectroscopy. Our results show that in contrast to freshly isolated neutrophils, neutrophil cells aged for 20 h in vitro had marked differences in the levels of a number of endogenous metabolites including lactate, amino acids and phosphocholine (PCho). There was no change in the concentration of taurine or glutamate and the ATP/ADP ratio was not affected. Levels of glutamine and lactate actually decreased. Identical changes were also observed in neutrophils stimulated to undergo apoptosis over a shorter time period (6 h) in the presence of TNFalpha and the phosphatidylinositol-3-kinase inhibitor wortmannin (WM). The changes in the concentration of PCho suggest possible activation of phospholipase associated with apoptosis or a selective failure of phosphatidycholine synthesis. The increased levels of apoptosis obtained with WM+TNFalpha, compared to TNFalpha by itself, suggest a synergistic effect by these compounds. The acceleration in rate of apoptosis probably arises from suppression by WM of pathway(s) that normally delay the onset of apoptosis. Changes in PCho and other endogenous metabolites, if proven to be characteristic of apoptosis in other cell systems, may permit non-invasive quantification of apoptosis. '

Adenosine Diphosphate↗

Relationships between bilayer structure and phospholipase A2 activity: interactions among temperature, diacylglycerol, lysolecithin, palmitic acid, and dipalmitoylphosphatidylcholine.

Bilayers composed of phosphatidylcholine initially resist catalysis by phospholipase A2. However, after a latency period, they become susceptible when sufficient reaction products (lysolecithin and fatty acid) accumulate in the membrane. Temperatures near the main bilayer phase transition and saturated long-chain diacylglycerol in the bilayer modulate the effectiveness of the reaction products. The purpose of this study was to identify possible mechanisms for these effects of temperature and diacylglycerol. Various fluorescent probes were used to asses changes in the ability of the reaction products to perturb the bilayer and promote enzyme binding to he membrane surface. Temperature appeared to cause three effects. First, the degree of binding of enzyme at the end of the latency period was greatest near the phase transition temperature where the latency was shortest. Second, the bilayer was more sensitive to perturbation by reaction products near the transition. Third, the disturbance provoked by the products was confined to the membrane surface below the transition but affected deeper regions at higher temperature where the latency period was greater. The latter two effects of temperature required the presence of calcium. Diacylglycerol promoted lateral segregation of reaction products in the bilayer. This effect corresponded with the tendency of diacylglycerol to reduce the length of the latency period at temperature below the phase transition. Therefore, it appeared that temperature affects the latency period by alternating the binding of the enzyme and the depth and magnitude of the bilayer perturbation caused by reaction products. Alternatively, diacylglycerol may enhance the effectiveness of reaction products by inducing them to segregate in the bilayer and thus create local regions of increased impact on the bilayer surface.

1,2-Dipalmitoylphosphatidylcholine↗

Development of a rapid and efficient magnetic resonance imaging technique for analysis of body fat distribution.

Fast scan magnetic resonance imaging techniques for adipose tissue (AT) quantification were compared to a conventional T1-weighted spin-echo (SE) sequence (TR = 500 ms, TE = 20 ms), imaging a mid-abdominal slice. A rapid T1-weighted SE sequence (TR = 36 ms, TE = 14 ms) was optimal, with minimal distortion (field, motion, flow artefact). Tissue contrast was higher and visceral AT was clearly differentiated. Quantification of all AT compartments (total, subcutaneous, internal, visceral) showed close agreement with the T1-weighted SE sequence and reproducibility was high (coefficient of variation < 4.7%). For AT quantification in a whole subject, this fast technique allows each image to be acquired serially at the magnet isocenter, as the subject is moved through the scanner (serial isocenter scanning, SIS). This method provides minimal image distortion and allows rapid coverage of the whole body.

Abdomen↗

Metabolic changes associated with vacuolation in murine models of scrapie using in vitro 1H-NMR spectroscopy.

In this study, metabolic changes in the 79A/C3H, ME7/VM, ME7/C3H, 87V/VM and 22A/SV scrapie mouse models were investigated during the clinical phase of the disease, using in vitro proton nuclear magnetic resonance spectroscopy. N-acetyl-aspartate was found to be significantly reduced in infected mice of the ME7/ C3H (40% reduction), ME7/VM (26%) and 79A/C3H (17%) models when compared to control mice, but not in the 87V/VM and 22A/SV models. The concentration of choline containing compounds and creatine remain unchanged in all models when compared with control murine brains. The level of N-acetyl-aspartate reduction correlated with the extent of grey-matter brain vacuolation. The levels of myo-inositol were found to be significantly increased in the ME7/VM (143%) and 79A/C3H (132%) models only and no significant changes were observed in the ME7/C3H, 87V/VM and 22A/SV models. These changes did not correspond to the severity of gliosis.

Animals↗

Automated feature extraction for the classification of human in vivo 13C NMR spectra using statistical pattern recognition and wavelets.

If magnetic resonance spectroscopy (MRS) is to become a useful tool in clinical medicine, it will be necessary to find reliable methods for analyzing and classifying MRS data. Automated methods are desirable because they can remove user bias and can deal with large amounts of data, allowing the use of all the available information. In this study, techniques for automatically extracting features for the classification of MRS in vivo data are investigated. Among the techniques used were wavelets, principal component analysis, and linear discriminant function analysis. These techniques were tested on a set of 75 in vivo 13C spectra of human adipose tissue from subjects from three different dietary groups (vegan, vegetarian, and omnivore). It was found that it was possible to assign automatically 94% of the vegans and omnivores to their correct dietary groups, without the need for explicit identification or measurement of peaks.

Adipose Tissue↗

An in vivo 13C magnetic resonance spectroscopic study of the relationship between diet and adipose tissue composition.

13C magnetic resonance spectroscopy (MRS) is a noninvasive technique used in the study of lipids. We applied 13C MRS to assess the effects of long-term dietary variation on adipose tissue composition in humans. In vivo 13C MRS was used to analyze the fatty acid composition of adipose tissue in 88 healthy volunteers with significantly different diets (38 vegans, 11 vegetarians, and 39 omnivores) assessed by analysis of dietary records. Results were compared with the serum lipid profile. 13C MRS revealed clear differences in the adipose tissue composition of vegans, which contained more unsaturated (P < 0.01) and fewer saturated fatty acids (P < 0.01) compared with omnivores and vegetarians. The vegan subjects had a significantly lower intake of saturated fatty acids and higher intake of polyunsaturated fatty acids than either the omnivore or the vegetarian groups (P < 0.01). These findings were associated with significantly lower levels of serum total cholesterol and low density lipoprotein-cholesterol in the vegan group compared with the omnivores. Our results demonstrate the use of 13C MRS for the noninvasive study of adipose tissue composition and its application to the study of the interaction between long-term dietary and metabolic risk factors in humans.

Adipose Tissue↗

Australian deliberations on access to its terrestrial and marine biodiversity.

The predominantly developed country business principle that the natural resource is effectively free, or of very low monetary value, has been significantly challenged in recent years, not only through the recognition of the accelerated rate of depletion of native forest resources and of the space and food demands of increasing populations, but also through international conventions which deal with a wide range of topics from the rights of indigenous people to the Law of the Sea Convention. Australia, classified as a developed country, but located in a geographic region of many developing countries, has, in the past 25 years, demonstrated particular concern for the rights of the people of those countries, as well as for the rights of indigenous people of Australia. The practical international aspects were clearly exemplified in the time, from 1985, when the Australian Institute of Marine Science (AIMS) negotiated, within the National Cancer Institute (NCI) contract, that collections of biological samples in developing countries would be accompanied by an agreement to provide benefits arising from field work, and from any commercial product developments, to those countries. Australia, as a signatory to the Convention on Biological Diversity (Appendix I), continues to analyze the challenge presented by the need to freely exchange genetic resources of common value, e.g. food crops, while insuring an appropriate reward to developing and developed countries, should discoveries be made from their biological resources, which lead directly or indirectly, to high value commercial non-food products. The Prime Minister's Coordinating Committee on Science and Technology established a special working group to recommend on access to Australia's biodiversity. The report arising from the study, and other related issues, are discussed.

Animals↗

Hepatic phosphorus-31 magnetic resonance spectroscopy in primary biliary cirrhosis and its relation to prognostic models.

BACKGROUND: In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) provides biochemical information about phosphorus metabolism. AIM: To assess 31P MRS as a prognostic marker in patients with primary biliary cirrhosis (PBC) in relation to the current clinical prognostic models. PATIENTS AND METHODS: Twenty three patients with PBC of varying functional severity and 16 matched healthy volunteers were studied using in vivo 31P MRS. Spectra were acquired using a 1.5 T spectroscopy system. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) and nucleotide triphosphate (NTP) were calculated. Pugh score, Christensen prognostic index, and R value according to the Mayo model were calculated from the clinical data. RESULTS: The PME/NTP, Pi/NTP, PME/PDE, and PME/Pi ratios and the PME signal height ratio (SHR) were significantly higher, while the PDE/NTP and PDE/SHR were significantly lower in PBC patients compared with healthy volunteers (p < 0.01). Significant correlations were seen between PME/Pi ratio and the prognostic index according to Christensen (r = 0.63, p < 0.001), R value according to the Mayo model (r = 0.45, p < 0.03), and with the Pugh score (r = 0.55, p < 0.007). CONCLUSIONS: This study shows that PME/Pi ratio obtained from 31P MRS correlates well with all three of the commonly used models of prognosis in patients with PBC. A longitudinal study with larger number of patients is required to confirm these findings and elucidate the biochemical changes underlying this phenomenon.

Adult↗