The Northern Ireland dietary survey and related studies.
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Adolescent↗
Biomedical subjects
M E Barker
Publications and source records attributed to M E Barker.
Simultaneous measurement of free-living energy expenditure by the doubly labeled water method and heart-rate monitoring.
Total energy expenditure (TEE) was measured simultaneously in 14 free-living adults over 15 d by the doubly labeled water (DLW) method and for 2-4 separate days by heart-rate (HR) monitoring. Individual curves for HR vs oxygen consumption (VO2) were obtained and an HR (FLEX HR: 97 +/- 8 beats/min, range 84-113 beats/min) that discriminated between rest and activity was identified. Calibration curves were used to assign an energy value to daytime HR above FLEX HR. Below FLEX HR energy expenditure was taken as resting metabolism. Sleeping energy expenditure was assumed to be equal to basal metabolic rate. Average HR TEE (12.99 +/- 3.83 MJ/d) and average DLW TEE (12.89 +/- 3.80 MJ/d) were similar. HR TEE discrepancies ranged from -22.2% to +52.1%, with nine values lying within +/- 10% of DLW TEE estimates. The FLEX HR method provides a close estimation of the TEE of population groups. However, an increased number of sampling days may improve the precision of individual estimates of TEE.
Activities of Daily Living↗
The diets of men in four areas of the UK: the Caerphilly, Northern Ireland, Edinburgh and Speedwell studies.
Nutrient intakes in four areas of the UK were compared, 7-d weighed intake data were obtained for representative community samples of middle-aged men in Caerphilly (South Wales), Northern Ireland, Edinburgh and Bristol (Speedwell). Intakes of energy were higher in Edinburgh than in the other three areas, but following allowance for this, differences in nutrient intakes were very small. The exceptions were P/S ratio and alcohol consumption. The P/S ratio for Northern Ireland (0.38) was considerably higher than that for the other areas (0.30 to 0.32). The proportion of heavy drinkers was higher in Edinburgh (15 per cent) than in other areas (5-9 per cent) and the proportion of abstainers was highest in Northern Ireland (38 per cent). Differences in nutrient intakes did not parallel the differences in ischaemic heart disease (IHD) mortality rates between the areas.
Alcohol Drinking↗
Regulation of cholesterol metabolism in the ethionine-induced premalignant rat liver.
The early premalignant liver provides a model in which to study metabolic alterations that may be permissive for the development of full malignancy. Although there are biochemical changes in this model, there are no detectable morphological ones when compared with a normal, fully differentiated liver. The maintenance of cholesterol homeostasis, essential for proper functioning of mammalian cells, is known to be altered in malignancy. We used the ethionine-induced premalignant liver model to study the effects of the premalignant state on cellular parameters involved in the maintenance of hepatic cholesterol homeostasis. Cholesterol synthesis was elevated about twofold in the livers of rats treated with ethionine as was the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, its rate limiting enzyme. There was no change in reductase activation state. Acyl coenzyme A:cholesterol acyl-transferase (ACAT) was decreased about 30%, and cholesterol 7 alpha-hydroxylase, about 50%. There was no significant change in neutral cholesteryl ester hydrolase activity, but acid hydrolase activity was decreased. There was little change in low density lipoprotein receptor protein as determined by immunoblotting. Biliary lipid secretion was in the normal range when expressed per gram liver; however, bile flow was doubled. The ethionine-fed animals were mildly hypocholesterolemic and had an altered serum lipoprotein pattern. Cholesterol synthesis and HMG-CoA reductase activity exhibited decreased sensitivities to inhibition by dietary cholesterol when compared to control livers. However, sensitivity to intragastrically administered mevalonolactone was not altered. Although ACAT activity was increased by mevalonolactone administration to levels similar to those in untreated animals, it was not increased in the ethionine-fed animals by feeding cholesterol. The ethionine-induced premalignant liver responded to ethinyl estradiol treatment in a manner similar to that of the control, i.e., profound hypolipidemia, increased low density lipoprotein receptors, decreased reductase activity, and increased cholesterol esterification. Thus, these livers retained their estrogen responsiveness. Taken together, the data demonstrate that the major elements involved in maintaining hepatic cholesterol homeostasis are present in the premalignant liver, although in some cases at levels that are different from the control. However, the susceptibility to regulation was altered in these livers to suggest markedly decreased availability of cholesterol of exogenous origin to the regulatory compartment(s). Further, coupling of the different elements involved in maintenance of hepatic cholesterol homeostasis appeared to have been changed.
Animals↗
Erythropoietin binding and induced differentiation of Rauscher erythroleukemia cell line red 5-1.5.
We isolated from the Rauscher erythroleukemia cell line (Red 5), a subclone (Red 5-1.5), which contains erythropoietin (epo) binding sites and demonstrates an epo-dependent erythroid differentiation. One class of high affinity binding sites was detected with a Kd (+/- S.D.) of 0.43 +/- 0.09 nM and a mean density/cell of 1200 +/- 311. The cell-associated 125I-epo was displaced by nonlabeled epo but not by other hormones or factors. The 125I-epo binding to Red 5-1.5 cells was maximal within 3 h at 15 degrees C and 1 h at 37 degrees C and proportional to cell number. The addition of epo increased [3H] uridine incorporation into RNA by 6 h and [3H]thymidine incorporation into DNA by 60 h followed by 59Fe incorporation into protein, cell proliferation, and formation of hemoglobin-containing colonies. The incorporation of 59Fe into protein demonstrated a linear dose response (from 0.002 to 1.5 units of epo/ml) beginning 60 h after addition of the hormone to the cultures, and there was a dose-dependent increase (from 0.1 to 1.0 unit of epo/ml) in the formation of hemoglobin-containing colonies. We concluded that the binding of 125I-epo to Red 5-1.5 suggests the presence of specific epo receptors. The sequence of the epo-induced proliferation and differentiation events is similar to primary erythroid cultures but requires longer epo exposure. Receptor occupancy correlates with the induced biological response.
Animals↗
Acinar heterogeneity of fatty acid binding protein expression in the livers of male, female and clofibrate-treated rats.
Liver fatty acid binding protein may play a role in the intracellular transport and compartmentation of long-chain fatty acid metabolism. The distribution of liver fatty acid binding protein in the hepatic acinus was determined by means of immunocytochemistry as well as by measurement of liver fatty acid binding protein in cellular protein selectively released from zone 1 and zone 3 cells by means of anterograde and retrograde liver perfusion with digitonin. In untreated male rats, specific immunocytochemical staining for liver fatty acid binding protein showed a declining portal-to-central hepatocellular gradient in intensity, consistent with the portal-to-central ratio of liver fatty acid binding protein abundance measured in effluents from digitonin-perfused livers of 1.6:1. Female and clofibrate-treated male rats, in both of which hepatic synthesis and abundance of liver fatty acid binding protein are greater than in untreated males, differed as well in the pattern of acinar expression of this protein. In females, periportal concentrations of liver fatty acid binding protein determined from the effluent of livers perfused anterograde with digitonin were similar to male values, whereas liver fatty acid binding protein concentration in pericentral hepatocytes determined from the effluent of retrograde perfused livers was increased, resulting in a marked attenuation of the portal-to-central gradient of this protein; this was also apparent on immunocytochemistry. Clofibrate-treated rats, in contrast, displayed a panacinar increase in liver fatty acid binding protein with maintenance of the portal-to-central ratio observed in untreated males. We conclude that there exists a declining portal-to-central gradient in liver fatty acid binding protein cellular abundance in the hepatic acinus of untreated male rats. Furthermore, the increased synthesis and abundance of liver fatty acid binding protein in female and clofibrate-treated male rats results in two different alterations in the acinar expression of this protein, i.e. a pericentral increase (female) or a panlobular increase (clofibrate). Elucidation of the relationship between the zonation of hepatic fatty acid metabolism and the acinar expression of liver fatty acid binding protein should provide a more detailed understanding of the function of this protein.
Alanine Transaminase↗
Effect of oxidative iodination of epidermal growth factor on its binding and secretion by hepatocytes.
Experiments were undertaken to determine whether the method of iodination of epidermal growth factor (EGF) affects its binding to rat liver plasma membranes and its uptake, processing, and secretion into bile by intact rat hepatocytes. EGF was iodinated using one of three oxidative reagents: chloramine T (CT), lactoperoxidase (LP), or monochloride (MC). Quantitative receptor binding studies on plasma membranes isolated from male rat livers with either CT-, LP-or MC-125I-EGF indicated no significant difference in the apparent binding constants of the three preparations. To determine whether these three preparations were capable of forming a covalent-like complex with the EGF receptor, they were individually incubated with isolated plasma membranes and subjected to polyacrylamide gel electrophoresis under reducing conditions, followed by autoradiography. Each preparation formed a major radioactive protein band of approximately 180 kD, identified as the EGF receptor by immunoprecipitation with monoclonal anti-EGF receptor antibodies. Furthermore, even unlabeled EGF incubated with plasma membranes formed this same 180 kD band, as revealed on Western blots using anti-EGF antibody. The biliary secretion of CT-, LP-, and MC-125I-EGF was compared by injecting each one into rat portal veins and measuring the total and immunoprecipitable radioactivity in bile. The amount of immunologically intact CT-125I-EGF in bile was significantly greater than the others, whereas MC-125I-EGF transport was significantly reduced. We conclude that the method of iodination does not affect the covalent-like binding properties of EGF. Furthermore, since unlabeled EGF displayed these same binding properties, oxidative iodination procedures per se do not account for the covalent-like association between EGF and its receptor. However, the method of iodination used did affect the intracellular transport and processing of EGF by hepatocytes. The structural modification responsible for this alteration in transport properties has yet to be determined.
Animals↗
Anatomic correlates of bacterial cholangiovenous reflux.
The purpose of these studies was to define the pathways by which bacteria pass from bile duct to bloodstream during acute bacterial cholangitis in the rat. The respective roles of biliary obstruction and intrabiliary pressure during the reflux of biliary bacteria were defined by the infusion of bacteria via the bile duct into rats with or without prior bile duct obstruction. As determined by quantitative blood culture analysis, bacterial reflux from bile to blood was enhanced by increased intrabiliary pressure regardless of presence or absence of biliary obstruction. Light microscopic examination of rat liver 48 hours after bile duct obstruction revealed bile ductular proliferation and bile canalicular dilatation. Light microscopic autoradiographs showed aggregates of tritiated thymidine-labeled Escherichia coli outside of interlobular bile ducts in the portal tracts. Transmission electron microscopic examination of rat liver perfused with a bacterial suspension via the common bile duct showed disruption of liver cells and formation of intracellular vacuoles. Bacteria appeared to enter the sinusoidal spaces via these intracellular vacuoles. We conclude that during retrograde biliary infusion (1) increased intrabiliary pressure is the main determinant of increased bacterial reflux into blood; (2) bacteria enter the bloodstream by predominantly intracellular pathways; and (3) prior biliary obstruction is not a significant factor in bacterial reflux from bile to bloodstream.
Animals↗
Good backs and bad backs: a general practice survey.
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Back Pain↗
Isoflurane as an anesthetic for experimental animal surgery.
Isoflurane is an inhalational anesthetic agent associated with no known hepatic toxicity. Despite this fact, isoflurane has not been widely utilized as an anesthetic agent in studies of liver structure and function in experimental animals. For this reason, livers from rats treated with pentobarbital or diethylether were compared to those from rats treated with isoflurane to determine differences in biochemical and morphologic parameters. Liver from pentobarbital-treated rats showed a significant decline in glutathione-S-transferase activity compared to liver from isoflurane/O2 or ether-treated rats. Liver microsomes from isoflurane/O2-treated rats retained more cytochrome-C(P450)-reductase activity than did those from pentobarbital-treated, ether-treated, or decapitated rats. Despite these biochemical alterations, morphometric analysis of liver from isoflurane/O2 and pentobarbital-treated rats showed no quantitative or qualitative differences in liver structure or organelle volume densities. Neither were differences detected in uptake and distribution of 125I-epidermal growth factor when analyzed by electron microscopic autoradiography. These data show that isoflurane with supplemental O2 has no effects on hepatic structure and fewer effects on hepatic function than other anesthetics and may be a better experimental anesthetic than any currently in use.
Anesthesia, General↗
Translocation of epidermal growth factor to the hepatocyte nucleus during rat liver regeneration.
To determine the fate of exogenous epidermal growth factor (EGF) in regenerating liver, 125I-labeled EGF was injected into rat portal veins at various times after 70% hepatectomy. Epidermal growth factor was taken up by the liver remnant at all time points studied (0, 4, 8, 16, and 36 h), but at 8 h after hepatectomy a large quantity was retained by the liver and EGF degradation products appearing in the bile decreased markedly. Electron microscopic autoradiography of the regenerating livers 1 h after injection of 125I-EGF demonstrated that 27% of the grains were associated with hepatocyte nuclei compared to 0.5% in shamoperated controls. There was also a concomitant decrease in grains associated with the lysosomal compartment. Nuclei isolated from regenerating livers exposed to 125I-EGF also demonstrated a three-fold increase in radioactivity compared to nuclei from control livers. Nearly 70% of nuclear radioactivity was precipitable with a specific antibody to EGF, and a small fraction appeared to be part of a high molecular weight complex. These data support the hypothesis that during the pre-S phase of liver regeneration, EGF is translocated to the nucleus rather than to lysosomes, and may participate in the initiation of deoxyribonucleic acid synthesis or alteration of gene expression.
Animals↗
A classification of back pain in general practice.
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Back Pain↗
Community children's homes.
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Adolescent↗
Increased hepatic density and phospholipidosis due to amiodarone.
Amiodarone is an amphiphilic iodinated compound that is used as a treatment for refractory ventricular arrhythmias. During evaluation for possible pulmonary toxicity, a patient receiving amiodarone was noted to have an increase in the density of his liver as seen on computed tomographic (CT) scanning of the abdomen. Six additional patients who were receiving amiodarone were subsequently evaluated to ascertain the frequency of this finding. The CT density of the liver was increased in all patients. Values obtained varied from 95 to 145 H, with a mean of 117 +/- 8.9 (normal, 30-70). The alkaline phosphatase was elevated in four patients, but only one had an elevation of either the alanine or aspartate aminotransferase. Two patients underwent liver biopsies, and both revealed membranous lamellar phospholipid-containing structures within hepatocytes. Animal studies done to recreate these findings revealed that amiodarone accumulated in the liver at concentrations 175-500 times greater than those found in serum. Quantitative measurements of iodine in samples from the same liver showed that the iodine levels were correspondingly elevated. In the treated animals, there was a small but statistically significant increase in the CT density of the liver, whereas the values for untreated animals were unchanged. Treatment with amiodarone leads to an accumulation in the liver of this iodinated compound and hence an increase in the CT density of the liver. This accumulation of the drug in hepatic lysosomes apparently causes a secondary phospholipidosis.
Aged↗
Transport of epidermal growth factor by rat liver: evidence for a nonlysosomal pathway.
Epidermal growth factor (EGF), circulating in the blood, is taken up by rat liver hepatocytes by means of specific and saturable receptor-mediated endocytosis. These experiments were undertaken to determine (a) the transport pathway(s) of EGF taken up by rat liver and (b) the effects of lysosomal inhibition on its transport. 125I-EGF was injected into rat portal veins, and bile samples were collected and analyzed for both total and immunoprecipitable radioactivity. In addition, the livers were examined by electron microscopic autoradiography. Some animals received injections of chloroquine before surgery, to disrupt lysosomal function. The results indicate that most of the EGF taken up by the hepatocytes is transported to lysosomes and degraded. However, a small but significant percentage of endocytosed EGF is transported by a pathway independent of the lysosomal system, resulting in secretion of intact EGF: (a) Both degraded and immunoprecipitable EGF are secreted into bile. (b) Immunoprecipitable radioactivity peaks at 20 min after EGF injection, whereas degradation-associated radioactivity does not peak until 40 min postinjection. (c) EGF isolated from bile is specifically taken up by isolated hepatocytes in monolayer culture, indicating that it is still recognizable by the EGF receptor. (d) When the lysosomal system is inhibited with chloroquine, secretion of degraded EGF is significantly inhibited, whereas the amount of intact EGF secreted into bile is unchanged. The utilization by liver of a dual transport process for EGF represents an unusual system of intracellular ligand processing, whose physiological significance has yet to be determined.
Animals↗
Behçet's syndrome: a case study.
This is the case report of a woman who for many years was a diagnostic puzzle. Her various problems were eventually identified as features of Behçet's syndrome, which is uncommon in this country. Besides the known clinical symptoms of the disease, this patient has suffered intermittently from dysmenorrhoea and menorrhagia, which may well be features of this disorder which have not previously been documented. There is no sign of remission for this patient, but awareness of her condition should lead to more sympathetic management of these cases.
Adult↗
Pain in the back and leg: a general practice survey.
Over a two-year period, the data on all patients in a general practice with back and leg pain were recorded in a standardized way. Two broad categories were distinguished, those with low-back pain syndromes and those with back and leg pain syndromes. Within the former, four patterns of pain distribution could be indentified, and the latter were sub-divided according to severity, history, and neurological involvement. History, clinical features, and outcome correlated with these various types. The majority of these patients may be managed conservatively at home, only a small proportion requiring referral for specialist advice or treatment. It is suggested that the intervertebral disc can account for only a small proportion of these problems.
Acute Disease↗
Unusual cause of urinary obstruction.
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Aged↗