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Biomedical subjects

J D Bell

Publications and source records attributed to J D Bell.

At least 91 records · Page 5Linked to original sources
PubMed1996

Cocaine and exercise: alteration in carbohydrate metabolism in adrenodemedullated rats.

The combined treatment of cocaine-exercise (CE) causes an exaggerated catecholamine response, a rapid depletion of muscle glycogen, and accumulation of lactic acid. To assess the contribution of the adrenal medulla in the catecholamine response and to determine the role of epinephrine (Epi) on carbohydrate metabolism, cocaine (20 mg/kg ip) or saline was injected into sham-operated (Sham) or adrenodemedullated (AdM) rats, which then ran for 5 min at 56 m/min, 0% grade. In Sham rats, CE caused plasma Epi values (means +/- SE) to rise to 27.7 +/- 6.9 nM compared with 13.3 +/- 1.5 nM in saline-exercise (SE) and 0.8 +/- 0.2 nM in both AdM-CE and AdM-SE animals (P < 0.05). With minimal Epi in AdM, CE still caused glycogen to fall to lower levels (25.4 +/- 3.0 mumol/g vs. 40.5 +/- 2.4 mumol/g) and lactate to rise to higher levels (17 +/- 3 vs. 9 +/- 1 mumol/kg) in white vastus muscle than in SE group (P < 0.05). CE had no significant effect on soleus and red vastus glycogenolysis but it did cause lactate accumulation in red vastus. As a result, plasma lactate levels were also higher after CE compared with SE in AdM (17.9 +/- 2.0 vs. 8.5 +/- 0.5 mM, P < 0.05). We conclude that during CE 1) Epi is not essential to the alteration in carbohydrate metabolism; 2) the latter may be related to the other catecholamines; 3) the adrenal medulla is the only source of Epi; and 4) the adrenal medulla is not the source of the increased levels of norepinephrine or dopamine.

Adrenal Medulla↗
PubMed1996

Cerebral metabolism within 18 hours of birth asphyxia: a proton magnetic resonance spectroscopy study.

Proton magnetic resonance spectroscopy (1H MRS) was performed within 18 h of birth (median 13, range 4-18 h) on 16 term infants with clinical features of birth asphyxia. Ten infants with no evidence of birth asphyxia were studied as controls at 5-18 (median 8) h after birth. To detect delayed impairments in cerebral energy metabolism, 15 infants suspected of asphyxia underwent 31P MRS at 33-106 (median 62) h of age. Choline, creatine, and N-acetylaspartate (NAA) were detected in spectra located to the basal ganglia in all infants. Lactate was detected in 15 of the 16 infants suspected of asphyxia, but in only 4 of the 10 controls (p < 0.05, chi 2). Glutamine and glutamate (Glx) was detected in 11 infants suspected of asphyxia and in three controls, but this difference was not significant at the 5% level. The spectra revealed no other significant differences between asphyxiated infants and controls. In the asphyxiated infants, there was a negative correlation between the ratio of lactate to creatine in the first 18 h of life and phosphocreatine/inorganic phosphate (PCr/ P(i)) at 33-106 h (p < 0.001). Five severely asphyxiated infants had PCr/P(i) < 0.75 (median 0.53, range 0.14-0.65), indicating a poor neurodevelopmental prognosis, and a further infant died before PCr/Pi could be measured. Ten infants had PCr/P(i) > 0.75 (1.03, 0.76-1.49). Median lactate/creatine was 1.47 (range 0.67-3.81) in the six severely affected subjects, 0.38 (0-1.51) in the latter group, and 0 (0-0.6) in controls (p < 0.0005, Kruskall-Wallis). These results suggest that, after birth asphyxia, cerebral energy metabolism is abnormal during the period when 31P MRS characteristically gives normal results. 1H MRS might be of value in predicting which infants are likely to suffer a decline in cerebral high energy phosphate concentrations and subsequent neurodevelopmental impairment.

Asphyxia Neonatorum↗
PubMed1996

Effects of n-3 fatty acids on the NMR profile of plasma lipoproteins.

The effects of fish oil supplementation (14.5 g n-3 fatty acids/day) on plasma lipoprotein particles in healthy volunteers were assessed by high resolution 13C and 1H nuclear magnetic resonance (NMR) spectroscopy. Resonances not previously observed in the 13C and 1H spectra of plasma and isolated lipoproteins were detected after fish oil ingestion. The 13C resonances, centered at 14.3, 127.1, and 131.6 ppm, have been assigned to specific carbon groups (CH3-CH2-CH = CH-, CH3-CH2-CH = CH-CH2-, CH3-CH2-CH = CH-CH2-, respectively) in eicosapentaenoic acid (C20:5n-3) and docosahexaenoic (C22:6n-3) DHA. The new lipid resonance observed in the 1H spectra of plasma (0.941 ppm) is consistent with the incorporation of these n-3 fatty acids into lipoprotein particles. The presence of increased EPA and DHA in plasma lipids was confirmed by gas-liquid chromatography. A marked reduction in the intensity of the methylene signal from very low density lipoproteins (VLDL) was also observed with fish oil. This reduction arises from a decrease in plasma triglyceride concentration (ca. 18%) and a reduction in the number of VLDL particles. Transverse relaxation studies of isolated VLDL and low density lipoprotein (LDL) showed significant elevation in the T2 of the -(CH2)n- and CH3- signals from non-n-3 fatty acids. The relaxation characteristics and signal intensity of the novel 1H peak (0.941 ppm) point to the existence of n-3 enriched microenvironments within lipoprotein particles. These findings suggest that incorporation of EPA and DHA into VLDL and LDL, after fish oil ingestion, leads to significant alteration in the molecular architecture of lipoprotein particles.

Adult↗
PubMed1995

Cirrhosis of the human liver: an in vitro 31P nuclear magnetic resonance study.

Human livers with histologically proven cirrhosis were assessed using in vitro 31P NMR spectroscopy. Spectra were compared with those from histologically normal livers and showed significant elevations in phosphoethanolamine (PE) and phosphocholine (PC) and significant reductions in glycerophosphorylethanolamine (GPE) and glycerophosphorylcholine (GPC). There were no significant differences in spectra from livers with compensated and decompensated cirrhosis. These results help to characterise the alterations in membrane metabolism in cirrhosis of the liver.

Ethanolamines↗
PubMed1995

Effects of temperature and glycerides on the enhancement of Agkistrodon piscivorus piscivorus phospholipase A2 activity by lysolecithin and palmitic acid.

The effect of temperature and various glycerides to modulate the ability of lysolecithin and fatty acid to promote high phospholipase A2 activity was studied using dipalmitoylphosphatidylcholine large unilamellar vesicles as substrate. The length of the lag phase prior to the accumulation of sufficient hydrolysis products (lysolecithin and fatty acid) to support high phospholipase activity was shortest at temperatures near the thermotropic phase transition of the phospholipid substrate. A reduction in the lag phase correlated with a reduction in the requirement for hydrolysis products at the phase transition temperature, where the bilayer exists in a state of fluctuating domains of gel and liquid crystal. Dipalmitoylglycerol and tripalmitoylglycerol also reduced the length of the lag phase. This reduction was both concentration-dependent and temperature-dependent relative to the phase transition in the presence of the glycerides. As with the effect of temperature, the ability of di- and triglycerides to decrease the lag time correlated with a decrease in the amount of reaction products necessary to promote high phospholipase activity. This effect coincided with the tendency of the glycerides to form domains in the bilayer. Glycerides that did not form domains either had no effect (monopalmitoylglycerol) or increased the length of the lag phase (dicaprylglycerol). These data suggest that the effect of the reaction products to increase phospholipase A2 activity is aided by the presence of fluctuations in lipid domains within the bilayer.

Agkistrodon↗
PubMed1995

Enhancement of Agkistrodon piscivorus piscivorus venom phospholipase A2 activity toward phosphatidylcholine vesicles by lysolecithin and palmitic acid: studies with fluorescent probes of membrane structure.

The activity of phospholipase A2 from snake venom to hydrolyze bilayers of phosphatidylcholines is greatly enhanced by the presence of the hydrolysis products, lysolecithin and fatty acid, in the bilayer. The fluorescence of several probes of membrane structure was used to monitor changes in bilayer physical properties during vesicle hydrolysis. These changes were compared to emission spectra and fluorescence polarization results occurring upon direct addition of lysolecithin and/or fatty acid to the bilayer. The excimer to monomer ratio of 1,3-bis(1-pyrene)propane was insensitive to vesicle hydrolysis, suggesting that changes in the order of the phospholipid chains were not relevant to the effect of the hydrolysis products on phospholipase activity. The fluorescence of 6-propionyl-2-(dimethylamino)-naphthalene (Prodan) suggested that the polarity of the bilayer in the region of the phospholipid head groups increases as the hydrolysis products accumulate in the bilayer. The fluorescence of 6-dodecanoyl-2-(dimethylamino)naphthalene (Laurdan) confirmed that such effects were restricted to the bilayer surface. Furthermore, the lysolecithin appeared to be the product most responsible for these changes. These results suggested that lysolecithin increases the activity of phospholipase A2 during vesicle hydrolysis by disrupting the bilayer surface, making the phospholipid molecules more accessible to the enzyme active site.

2-Naphthylamine↗
PubMed1995

Quantification of the interactions among fatty acid, lysophosphatidylcholine, calcium, dimyristoylphosphatidylcholine vesicles, and phospholipase A2.

The rate of hydrolysis of phosphatidylcholine bilayers by soluble phospholipase A2 (PLA2) is greatly enhanced by the presence in the bilayer of a threshold mole fraction of the reaction products: fatty acid and lysophosphatidylcholine (lyso-PC). The threshold requirement of these products appears to vary as a function of vesicle and calcium concentration. To further identify the roles of myristic acid, lyso-PC, and calcium in promoting optimal PLA2 activity, we have quantified the various interactions among these components and dimyristoylphosphatidylcholine large unilamellar vesicles. The bilayer/water partition coefficient for myristic acid was obtained by competition of vesicles for the binding of the fatty acid to an acrylodan conjugate of an intestinal fatty acid binding protein as monitored by the acrylodan fluorescence emission spectrum. The partition coefficient for lyso-PC was obtained by a similar procedure using the tryptophan emission spectrum of bovine serum albumin. The effect of calcium concentration on these interactions was also quantified. These results were incorporated into an empirical model to describe the threshold requirements for these products in the bilayer. This information is vital for elucidating the mechanism of activation of PLA2 by the hydrolysis products.

Calcium↗
PubMed1995

Quantification of biomedical NMR data using artificial neural network analysis: lipoprotein lipid profiles from 1H NMR data of human plasma.

Artificial neural network (ANN) analysis is a new technique in NMR spectroscopy. It is very often considered only as an efficient "black-box' tool for data classification, but we emphasize here that ANN analysis is also powerful for data quantification. The possibility of finding out the biochemical rationale controlling the ANN outputs is presented and discussed. Furthermore, the characteristics of ANN analysis, as applied to plasma lipoprotein lipid quantification, are compared to those of sophisticated lineshape fitting (LF) analysis. The performance of LF in this particular application is shown to be less satisfactory when compared to neural networks. The lipoprotein lipid quantification represents a regular clinical need and serves as a good example of an NMR spectroscopic case of extreme signal overlap. The ANN analysis enables quantification of lipids in very low, intermediate, low and high density lipoprotein (VLDL, IDL, LDL and HDL, respectively) fractions directly from a 1H NMR spectrum of a plasma sample in < 1 h. The ANN extension presented is believed to increase the value of the 1H NMR based lipoprotein quantification to the point that it could be the method of choice in some advanced research settings. Furthermore, the excellent quantification performance of the ANN analysis, demonstrated in this study, serves as an indication of the broad potential of neural networks in biomedical NMR.

Humans↗
PubMed1995

MRI assessment of the blood-brain barrier in a hamster model of scrapie.

Magnetic resonance (MR) imaging in combination with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhancement was used to investigate the integrity of the blood-brain barrier in a hamster model of scrapie (263K) during the clinical phase of the disease. The post Gd-DTPA images of the infected hamster brain showed marked enhancement, which was not present in control animals. These results suggest that blood-brain barrier function is disrupted in the clinically-affected animal.

Animals↗
PubMed1995

Effect of functional grade and etiology on in vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: biochemical basis of spectral appearances.

Hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) was undertaken in 85 patients with histologically proven cirrhosis of varying etiologies and functional severity. Reference data were acquired from 16 healthy volunteers who had no history or evidence of liver disease or alcohol abuse. In vivo hepatic 31P MR spectra were acquired with pulse angle 45 degrees and repetition times (TR) of 5 and 0.5 seconds. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) relative to beta ATP, and of PME relative to PDE were calculated from spectra acquired at TR 5 seconds. Estimates of saturation effects for individual resonances were obtained by dividing the peak height at TR 5 seconds by that at TR 0.5 seconds to yield a T1-related signal height ratio (SHR). When compared with reference values, the patients with liver disease showed a significantly higher PME/ATP (P < .0001), PME/PDE (P < .0001), PME SHR (P < .001), and Pi SHR (P < .02), and a lower PDE/ATP (P < .001) and PDE SHR (P < .001). The magnitude of these changes increased significantly and progressively with increasing functional impairment. In patients with compensated cirrhosis spectral appearances varied with etiology; thus, patients with postviral cirrhosis showed a significantly higher Pi/ATP; those with alcoholic cirrhosis, a significantly lower PDE/ATP; and those with cirrhosis secondary to primary sclerosing cholangitis, a significantly lower Pi/ATP than the healthy volunteers or other etiological groups. However, spectral appearances did not vary with etiology in patients with decompensated disease. In vitro 31P MRS of perchloric extracts of samples of liver tissue obtained from 10 patients with cirrhosis at transplant hepatectomy showed increases in levels of the soluble PME metabolites, phosphorylcholine and phosphorylethanolamine, and reductions in the levels of the soluble PDE metabolites, glycerophosphorylcholine and glycerophosphorylethanolamine. These changes suggest regenerative activity in cirrhotic livers. The increases in soluble phosphomonoesters in the aqueous extracts accounted for the increased PME/ATP ratio seen in the in vivo spectra, and might account for the increase in PME SHR. The reduction in soluble phosphodiesters in the aqueous extracts did not entirely account for the reduction PDE/ATP ratio seen in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1994

Microsatellite instability in ulcerative colitis-associated colorectal dysplasias and cancers.

Microsatellites are short nucleotide repeat sequences present throughout the human genome. Alterations of microsatellites, comprising extra or missing copies of these sequences, have been termed microsatellite instability. This abnormality occurs in sporadic and hereditary adenocarcinomas of the proximal colon, as well as in many other tumor types. We determined whether microsatellite instability occurred in ulcerative colitis-associated cancers or precancerous dysplasias. Sixty-three patients were evaluated, consisting of 188 samples of genomic DNA (63 normal controls, 68 cancers, 52 dysplasias, and 5 adjacent tissues) at loci D2S119, D2S123, D2S147, D10S197, and D11S904. Multiplex polymerase chain reaction was performed using one radiolabeled nucleotide, and the products were electrophoresed on denaturing polyacrylamide gels. Seventeen of the 63 patients (27%) possessed lesions showing instability at 1 or more loci. Fourteen of 68 tumor samples (21%) and ten of 52 dysplasias (19%) displayed instability. There was no tendency for a greater number of loci to manifest instability in more advanced lesions. Neither anatomic location nor loss of heterozygosity at the p53 locus were associated with microsatellite instability by 2-way table analysis. These data support a role for defective DNA repair in the generation of a subset of both early and advanced ulcerative colitis-associated colorectal neoplastic lesions.

Colitis, Ulcerative↗
PubMed1994

Quantification of the interaction between lysolecithin and phospholipase A2.

The rate of hydrolysis of phosphatidylcholine bilayers by phospholipase A2 may be either enhanced or inhibited by the presence of lysolecithin depending on the experimental conditions examined. To further understand the relationship of lysolecithin to phospholipase A2 activity, the binding of lysolecithin to phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus was examined by fluorescence spectroscopy. The tryptophan emission intensity of the enzyme was enhanced by 70% upon addition of lysolecithin. The binding isotherm for lysolecithin to the phospholipase A2 estimated from the fluorescence change was biphasic, with a clear break in the curve occurring at the critical micelle concentration of the lysolecithin. Several observations suggested that the phospholipase A2 was capable of hydrolyzing the lysolecithin although at a rate far below that of phospholipid hydrolysis. These experiments were repeated using several other species of phospholipase A2, and the results were found to be general among the enzymes except the lys-49 isozyme from A. p. piscivorus which displayed neither the dependence on the critical micelle concentration for binding nor the ability to hydrolyze lysolecithin. These results were used as the basis for a quantitative analysis of enzyme fluorescence changes that occur during the time course of phospholipid hydrolysis and of the mechanism whereby lysolecithin inhibits the hydrolysis of phosphatidylcholine bilayers by phospholipase A2.

Agkistrodon↗
PubMed1994

Effect of fish oil on cancer cachexia and host liver metabolism in rats with prostate tumors.

The aim of this study was to investigate whether tumor-induced cachexia and aberrations in host liver metabolism, induced by the MAT-LyLu variant of the Dunning prostate tumor, could be prevented by omega 3 fatty acids from fish oil. On day 0, adult Copenhagen-Fisher rats fed normal chow ad libitum were inoculated with 10(6) MAT-LyLu cells (n = 14) or saline (n = 9). On day 7, when tumors were palpable, four tumor-bearing (TB) and four nontumor-bearing (NTB) rats were put on isocaloric diets with 50% of total energy as fish oil. The introduction of fish oil-enriched diets caused a reduction in energy intake to less than half of the energy intake by animals fed normal diets during days 7-14 (difference by dietary group: NTB, P < 0.001; TB, P < 0.001). During days 14-21, energy intake in fish oil-fed animals returned to approximately 75% of energy intake by animals fed normal diets (difference by dietary group: NTB, P < 0.003; TB, P = 0.001). Carcass weight of animals on day 21, when the study was terminated, was significantly related to initial weight (P = 0.05) and mean food intake during the study (P = 0.01). When data were adjusted for these variables using analysis of covariance, with NTB animals on normal diets being the reference group, significant loss of carcass weight was observed in TB animals on normal diets only (mean +/- SEM 58 +/- 10 g loss, P < 0.001), but not in TB animals on fish oil diets (8 +/- 18 g loss, P = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Enhancement of adenylate cyclase activity in S49 lymphoma cell membranes by the toxin thionin from Pyrularia pubera.

We investigated the mode of action of Pyrularia thionin on adenylate cyclase in S49 lymphoma cell membranes. Thionin increased the forskolin-induced cAMP production in both wild-type and cyc- variant cell membranes. Thionin increased the apparent efficacy, but not potency, of the stimulation of adenylate cyclase by forskolin. Our results also indicated that the stimulatory G protein (Gs) was not involved in the action of thionin on adenylate cyclase; however, thionin appeared to reduce the effect of Gi on adenylate cyclase. We examined the effect of thionin on the temperature dependence of adenylate cyclase activity. The effect of thionin was not quantitatively the same at all temperatures. The effect was greatest in the range of about 30 degrees C to 50 degrees C. In addition, cardiotoxin, a structurally distinct peptide that alters the properties of biological membranes similarly to thionin, also enhanced the activity of adenylate cyclase. It seems reasonable to suspect that thionin influences the activity of adenylate cyclase indirectly by acting on the membrane.

Adenylyl Cyclases↗
PubMed1994

Utilization of uniformly labeled 13C-polyunsaturated fatty acids in the synthesis of long-chain fatty acids and cholesterol accumulating in the neonatal rat brain.

Polyunsaturated fatty acids are needed for normal neonatal brain development, but the degree of conversion of the 18-carbon polyunsaturated fatty acid precursors consumed in the diet to their respective 20- and 22-carbon polyunsaturates accumulating in the brain is not well known. In the present study, in vivo 13C nuclear magnetic resonance spectroscopy was used to monitor noninvasively the brain uptake and metabolism of a mixture of uniformly 13C-enriched 16- and 18-carbon polyunsaturated fatty acid methyl esters injected intragastrically into neonatal rats. In vivo NMR spectra of the rat brain at postnatal days 10 and 17 had larger fatty acid signals than in uninjected controls, but changes in levels of individual fatty acids could not be distinguished. One day after injection of the U-13C-polyunsaturated fatty acid mixture, 13C enrichment (measured by isotope ratio mass spectrometry) was similar in brain phospholipids, free fatty acids, free cholesterol, and brain aqueous extract; 13C enrichment remained high in the phospholipids and cholesterol for 15 days. 13C enrichment was similar in the main fatty acids of the brain within 1 day of injection but 15 days later had declined in all except arachidonic acid while continuing to increase in docosahexaenoic acid. These changes in 13C enrichment in brain fatty acids paralleled the developmental changes in brain fatty acid composition. We conclude that, in the neonatal rat brain, dietary 16- and 18-carbon polyunsaturates are not only elongated and desaturated but are also utilized for de novo synthesis of long-chain saturated and monounsaturated fatty acids and cholesterol.

Aging↗
PubMed1994

Cerebral phosphorus-31 magnetic resonance spectroscopy in patients with chronic hepatic encephalopathy.

Cerebral phosphorus-31 magnetic resonance spectroscopy was undertaken in 33 patients with biopsy-proven cirrhosis: 6 had no evidence of neuropsychiatric impairment on standard clinical, psychometric and electrophysiological testing; 8 had evidence of subclinical hepatic encephalopathy; and 19 were classified as having overt hepatic encephalopathy. The reference population comprised 15 healthy volunteers. Unlocalized spectra were acquired from the entire head with a 45-degree pulse angle and repetition times of 1 and 5 sec. Spectra localized to the basal ganglia were acquired with a 45-degree pulse angle and a repetition time of 1 sec. Peak area ratios of phosphomonoesters, inorganic phosphate, phosphodiesters and phosphocreatine relative to beta-ATP were measured in the spectra acquired. We noted no consistent change in the ratios of inorganic phosphate to ATP and phosphocreatine to ATP. Mean values of the ratios of phosphomonoesters to ATP and phosphodiesters to ATP were significantly lower in the total patient population than in the reference population, and they correlated with the patients' neuropsychiatric status. Thus we found no significant reductions in the mean ratios of phosphomonoesters to ATP and phosphodiesters to ATP in patients who were neuropsychiatrically unimpaired, but significant reductions were observed in the mean ratios of phosphomonoesters to ATP and phosphodiesters to ATP in patients with both subclinical and overt hepatic encephalopathy. The most marked reductions in these metabolite ratios were observed in patients with overt encephalopathy.

Adult↗
PubMed1993

A 31P and 1H-NMR investigation in vitro of normal and abnormal human liver.

Spectral changes in human hepatic tumours and possible systemic effects of tumour on host liver were assessed by 31P and 1H in vitro NMR spectroscopy. The 1H and 31P spectra from liver tumour biopsies showed significant elevation in phosphoethanolamine, phosphocholine, taurine, citrate, alanine, lactate and glycine, and significant reduction in GPE (glycerophosphoethanolamine), GPC (glycerophosphocholine), creatine and threonine compared to histologically normal tissue. 31P-NMR spectra obtained from histologically normal tissue within tumour-bearing livers showed significant elevation in phosphoethanolamine and phosphocholine compared to data from liver biopsies from nontumour-bearing patients (pancreatitis). These results suggest that alterations in membrane metabolism in host liver can be detected by 31P-NMR.

Biopsy↗