Linkage analysis of manic depression in an Irish family using H-ras 1 and INS DNA markers.
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Bipolar Disorder↗
Biomedical subjects
M Gill
Publications and source records attributed to M Gill.
Two outbreaks of foodborne gastroenteritis caused by a small round structured virus: evidence of prolonged infectivity in a food handler.
In two outbreaks of diarrhoea and vomiting that were caused by a small round structured virus (SRSV) that affected over 275 people, epidemiological and laboratory evidence showed that certain foods were the vehicles of infection and suggest that one of the chefs who prepared them may have been excreting this virus for a long time.
Carrier State↗
Pigments of fungi (Macromycetes).
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Fungi↗
An economic appraisal of screening for Down's syndrome in pregnancy using maternal age and serum alpha fetoprotein concentration.
The direct and indirect costs and benefits of expanding the existing screening programme for Down's syndrome by using maternal age and serum alpha fetoprotein concentrations have been calculated using an ascertainment of Down's syndrome pregnancies from the North East Thames Regions in 1982. In addition, a possible approach to evaluating the total costs and benefits to the families concerned is presented. If the uptake of the proposed screening programme is maximal, the replacement rate is zero and a discount rate of 5% is used, the benefit cost ratio is 23.6. If the uptake of the programme is 50%, the replacement rate is 100% and a discount rate of 7% is used, the benefit cost ratio is 12.2. The proposed screening programme, based upon a risk of Down's syndrome of at least 1 in 220 using maternal age and serum alpha fetoprotein is both equitable for families at risk and of economic benefit to both families and society.
Abortion, Induced↗
Metabolism of the lactating cow. I. Animal elements of a mechanistic model.
A mechanistic model of dairy cow metabolism is described. The model was constructed as part of a programme directed toward quantitative and dynamic analysis of concepts and data regarding factors which influence the partition of nutrients in lactating dairy cows. Sensitivity and behavioural analyses undertaken using the model indicate that concepts and data arising from tissue level experiments conducted in vitro can be used to structure and parameterize whole-animal models since the quantitative and dynamic behaviour of such a model is acceptable. These analyses indicate further that such models can be used to evaluate factors which influence patterns of nutrient utilization. By way of illustrating the model's utility regarding evaluation of concepts relating to the interpretation of energy balance experiments, results of a simulated energy balance experiment are presented. Apparent costs of milk synthesis are partitioned among biosynthetic costs, physiological costs, ion transport costs and the reductions in energy expenditures in synthesis of body components which accompany increasingly negative energy balances due to feed restriction.
Animals↗
Metabolism of the lactating cow. III. Properties of mechanistic models suitable for evaluation of energetic relationships and factors involved in the partition of nutrients.
Two models of lactating dairy cows were constructed by combining mechanistic models of digestion and metabolism reported previously and by adding elements to allow simulation of changes in tissue metabolic capacities over time. One model (day version) had an integration interval of 0.005 d and was suitable for simulation of within-day dynamics of nutrient supply and partition. The other (lactation version) had an integration interval of 1 d and was suitable for simulation of full lactation cycles. A number of simulation analyses were conducted to characterize and evaluate the models, to examine quantitative and dynamic properties of mechanisms which influence partition of nutrients, to identify aspects requiring further study, and to illustrate the potential usefulness of mechanistic, as compared to empirical, models in analyses of energy balance in lactating dairy cows.
Animal Nutritional Physiological Phenomena↗
Simulation of the metabolism of absorbed energy-yielding nutrients in young sheep: efficiency of utilization of acetate.
A previously described mathematical model that simulates the metabolism of absorbed nutrients was used to examine factors influencing the efficiency of utilization of acetate in a sheep weighing 25 kg. A significant component of the model was a function representing substrate cycles that degraded ATP when its concentration reached twice initial levels. Acetate utilization was simulated when up to 2 g mol/d were added to four diets (representing forages and concentrates) that supplied varying proportions of absorbed volatile fatty acids, glucose and protein. The basal diets provided either 4.375 (near energy balance) or 8.75 MJ/d absorbed energy. The predicted net efficiency of utilization (kf) of the energy in added acetate was high (0.58-0.70) for all combinations of absorbed nutrients at the low level of energy absorption, whereas at the higher level, it ranged from 0.16 (forage) to 0.49 (high protein concentrate). Low kf values were always associated with a considerable flux of ATP through the degradation pathway. The increase in ATP concentration that caused this pathway to operate was linked to an inhibition in the utilization of acetyl-CoA for fatty acid synthesis and an increase in its oxidation. The simulated addition of exogenous NADPH or its precursors (particularly glucose and propionate) to these diets repartitioned acetyl-CoA flux towards fatty acid synthesis instead of oxidation, decreased the flux of ATP through the degradation pathway and increased the kf of added acetate. Although a negative relationship was predicted between kf of added acetate and NADPH production for diets with increasing protein content, kf still depended on ATP flux through the degradation pathway. Addition of glucose to the high protein diets decreased this flux by decreasing acetyl-CoA oxidation and increasing fatty acid synthesis. The predictions suggest that the efficiency of acetate utilization in ruminants may be influenced by NADPH availability when a considerable amount of absorbed energy is derived from acetate. Increased absorption of glucose or propionate enhanced NADPH production, but the major effect on acetate utilization of increasing dietary protein was not through NADPH production.
Absorption↗
Simulation of the metabolism of absorbed energy-yielding nutrients in young sheep: efficiency of utilization of lipid and amino acid.
A previously described mathematical model that simulates the metabolism of absorbed nutrients in a sheep weighing 25 kg was used to examine the effects of altering lipid and amino acid absorption, and the potential of the animal to deposit protein on the efficiency of utilization (kf) of metabolizable energy. The predicted kf of energy from lipid added to several diets ranged from 0.65 to 0.74 and was influenced by both the protein and glucose content of the diet. The highest efficiency occurred when body protein deposition was limited by amino acid absorption. Lower values occurred with high protein diets when the proportion of body energy deposited as fat declined and, with low protein diets, when NADPH supply limited the synthesis of fatty acids from acetyl-CoA. Predicted kf of energy from amino acid added to several diets ranged from 0.003 to 0.47. Low values occurred when protein synthesis was limited by amino acid absorption; an increase in amino acid supply increased ATP utilization for protein synthesis and substantially reduced fat deposition with little resulting change in energy retention. The higher values occurred when most of the additional amino acid was oxidized. Glucose supply increased the kf of added amino acid primarily by reducing the synthesis of glucose from amino acids. Predicted kf of a whole diet generally declined as the proportion of protein in the diet increased. However, when the balance of absorbed nutrients was such that fat synthesis was limited by the supply of NADPH, kf increased with increasing dietary protein. Predicted kf of a diet also declined when the proportion of body energy deposited as protein increased, except when fat synthesis was limited by the supply of NADPH. The predictions suggest that kf is determined primarily by the energetic efficiency of biochemical reactions for maintenance and growth. However, most kf values less than 0.5 were associated with a flux of more than 1 g mol/d of ATP through the degradation pathway (representing substrate cycles) that occurred when NADPH supply limited the synthesis of fatty acids from acetyl-CoA.
Absorption↗
Cytotoxic studies in human newborns: lessened allogeneic cell-induced (augmented) cytotoxicity but strong lymphokine-activated cytotoxicity of cord mononuclear cells.
Nonspecific cytotoxic responses such as natural killer activity can be increased in vitro by incubating effector cells with soluble factors or allogeneic cells. We sought to determine if newborn cells, known to be deficient in most cytotoxic responses, including resting NK activity, could develop enhanced cytotoxic responses following incubation with allogeneic cells (augmented cytotoxicity) or with lymphokines (lymphokine-activated cytotoxicity). Cord whole mononuclear cells (WMC) incubated with irradiated Raji cells for 5 days develop lower levels of cytotoxicity toward K562 targets at both a 20:1 effector:target (E:T) ratio (39 +/- 2.7% vs 49 +/- 3.6%) and a 10:1 E:T ratio (29 +/- 2.6% vs 40 +/- 3.6%) than do adult cells. Lessened specific cytotoxicity of cord cells developed toward the sensitizing Raji cells was also observed at both E:T ratios. Attempts to enhance the induced cytotoxicity by incubation with interferon or isoprinosine were unsuccessful. In contrast, lymphokine (i.e., interleukin 2)-activated killer (LAK) cytotoxicity is not deficient in cord WMC. Indeed, the level of LAK cytotoxicity is equivalent to that observed with similarly treated adult cells despite a lower baseline level of cytotoxicity toward the target cells. In the presence of purified IL-2 for 5 days, cord WMC cytotoxicity against K562 cells increased from 12 +/- 2.6 to 71 +/- 4.2% and against Raji cells increased from 9.6 +/- 2.5 to 48 +/- 6.7%. Similarly treated adult cells increased their killing against K562 from 23 +/- 4.2 to 61 +/- 4.5% and against Raji from 12 +/- 3.0 to 36 +/- 5.3%. This substantial lymphokine-activated cytotoxicity of newborn cells suggests the possibility of therapeutic intervention with purified lymphokines in neonatal infections or neoplasms.
Cytotoxicity, Immunologic↗
The choice of a model for studying the hypothalamus-pituitary interactions in vitro.
Comparative studies on the release of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (Prl) by the whole pituitary, pituitary plus hypothalamus and pituitary-hypothalamus complex (PHC) were undertaken to choose an appropriate model for studying the hypothalamus-pituitary interactions in vitro and to relate the importance of the intact neural connections between pituitary and hypothalamus on hypothalamus-pituitary interactions. Also the effect of including dopamine (DA) at 1 X 10(-7) mol/1 in these different in vitro systems on the release of LH, FSH and Prl was investigated. The pituitary released increasing amounts of LH and FSH at 2, 4 and 6 h but the amount of Prl released remained unchanged. The rates of release of LH, FSH and Prl by the pituitary were different and were characteristic of each hormone. Co-incubation of pituitary with hypothalamus stimulated the release of LH and FSH but inhibited the release of Prl. Pituitary-hypothalamus complex behaved almost identical to behaved almost identical to pituitary plus hypothalamus system. Inclusion of 1 X 10(-7) M DA in the incubation medium stimulated the release of LH (80%) but inhibited the release of Prl (71%) by PHC. FSH was unaffected. DA had no significant effect on the release of LH, FSH and Prl by pituitary and pituitary plus hypothalamus systems. It is suggested that PHC is the system of choice for studying hypothalamus-pituitary interactions in vitro.
Animals↗
Metabolism of lactic acid isomers in the rumen of silage-fed sheep.
1. Four mature sheep were offered perennial ryegrass (Lolium perenne, cv. S23) silage (885 g dry matter/d) at hourly intervals. The silage was well fermented with a pH of 4.0, a lactic acid content of 139 g/kg dry matter and an organic matter digestibility of 0.766. 2. Continuous intraruminal infusions of 14C-labelled sodium salts of [U-14C]acetic acid, [2-14C]propionic acid, [2-14C]butyric acid and D- and L-[U-14C]lactic acid and an intravenous infusion of [U-14C]glucose were made on separate occasions to estimate the fluxes of rumen acetate, propionate, butyrate and lactate as well as plasma glucose. The data were resolved by the use of appropriate four-compartment (rumen) and three-compartment (rumen-plasma) models. 3. Irreversible loss rate (g C/h) of rumen acetate (5.32 g C/h) was considerably greater than values obtained for propionate (2.58), butyrate (2.80) and lactate (2.91). 4. Total flux of lactate (1.83 mol/d) exceeded the amount of lactate consumed in the diet (1.37 mol/d) indicating a net synthesis of 0.46 mol lactate/d. Approximately 0.90 of total lactate flux was metabolized in the rumen, with 1.00 mol/d converted to acetate, 0.57 to propionate and 0.08 to butyrate. The flux to acetate was significantly (P less than 0.05) greater than that to propionate. Both the D- and L-isomers appeared to have similar metabolic fates. 5. Lactate appeared to make no direct contribution to glucose flux in the animal, but 0.10 of total lactate was converted to glucose through propionate. 6. The results are discussed in relation to overall lactate metabolism, and it is suggested that almost 0.30 of ruminally digested organic matter may be fermented via lactate.
Animal Feed↗
The effect of digestibility and forage species on the removal of digesta from the rumen and the voluntary intake of hay by sheep.
1. The characteristics of digestion, passage and rumen fill of three hays: early- and late-cut perennial ryegrass (Lolium perenne cv. Endura) and white clover hay (Trifolium repens cv. Blanca and Pronitro) were studied using six rumen-cannulated sheep fed at a restricted level of intake (18 g dry matter (DM)/kg live weight (LW) per d), in a two 3 x 3 Latin square design. 2. Voluntary intake of the same diets was measured using a further six non-cannulated sheep in a similar design. 3. Rate of digestion of the three hays was measured using dacron bags and the rates of digestion of DM and neutral-detergent fibre (NDF) for clover hay were significantly (P less than 0.05 and P less than 0.001 respectively) faster than those for the two grass hays whose rates did not differ. Rates of passage, determined using chromium-mordanted hay, did not differ between treatments. 4. Rumen pool sizes of DM, organic matter and fibre were generally greatest for the late-cut grass hay and lowest for the clover hay, while voluntary intake was highest (P less than 0.001) for the clover hay (36.6 g DM/kg LW per d) and lowest for the late-cut grass hay (24.7 g/kg LW per d). 5. The net rate of removal of indigestible fibre from the rumen appeared to vary within the day, with maximal disappearance occurring during eating, followed by a lag phase between 5 and 10 h after feeding, with a second increase in rate between 10 and 24 h post-feeding.
Animal Feed↗
The effect of supplementation with maize starch and level of intake of perennial ryegrass (Lolium perenne cv. Endura) hay on the removal of digesta from the rumen of sheep.
1. Eight wether sheep were offered a diet of perennial ryegrass (Lolium perenne cv. Endura) hay once daily at two levels of intake (11 and 16.5 g dry matter (DM)/kg live weight (LW] with or without maize starch (175 g DM/kg hay DM). The experiment consisted of four periods, each lasting 32 d. Rates of digestion of the hay were measured by incubation in dacron bags and rates of passage using chromium-mordanted hay. Rumen pool sizes of DM, organic matter and fibre were measured by emptying the rumen. 2. The inclusion of starch in the diet appeared to increase significantly (P less than 0.01) the lag phase before the start of fibre digestion, as observed both in the dacron bag studies and in the slower initial disappearance of digestible neutral-detergent fibre (NDF) from the rumen recorded by emptying of rumen contents. However, there was no significant effect of starch on apparent digestibility of fibre in the whole tract. 3. The main effect of increasing the level of feeding was to increase the rate of passage with a consequent decrease in overall digestibility. The fractional rate of passage increased from 0.0318 to 0.0400 as the level of feeding increased, while apparent digestibility of NDF decreased from 0.755 to 0.724. 4. On all treatments the weight of indigestible fibre in the rumen remained more or less constant between 5, 10 and 15 h after feeding, but was significantly lower at 24 h. These results suggest that a high proportion of the outflow of material from the rumen not associated with feeding appears to occur during the second half of the feeding cycle.
Animals↗
Dynamic models: their use in understanding and predicting nutrient response.
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Amino Acids↗
Simulation of the metabolism of absorbed energy-yielding nutrients in young sheep.
A mathematical model is described, which simulates the metabolism of absorbed nutrients (amino acids, acetic acid, butyric acid, glucose, lipid and propionic acid) in growing sheep. The basic assumption of the model is that each nutrient is partitioned between synthetic, oxidative or intermediate reactions with rates of reaction which are described using enzyme kinetics. These rates depend on the relationship between maximum reaction rates, constants of affinity and inhibition and the concentrations of metabolites as determined by the model. Synthetic reactions calculate fat and protein deposition while intermediate reactions involve the production of ATP and NADPH. There is a total of twelve state variables and the model, programmed in CSMP and ACSL, is solved by integration of twelve differential equations. The model calculates the efficiency of utilization of metabolizable energy for different nutrient inputs and the results may be interpreted in terms of fluxes through the metabolite pools. Simulations using inputs representing forage- and concentrate-based diets indicated decreased efficiency for the forage at high levels of intake and possible reasons for this were further studied in simulations where the inputs of protein and glucose were varied.
Acetates↗
The effect of protein supplementation on digestion and glucose metabolism in young cattle fed on silage.
1. Ryegrass (Lolium multiflorum ev. RvP) silage was given to twelve Friesian steer calves (initial live weight (LW) 106 kg) at 2.3 kg dry matter (DM)/calf per d, alone, or with a supplement of fish meal at 50 (FM1) or 100 (FM2) g/kg silage DM per d. 2. The rate of flow of nutrients into the duodenum was measured using a dual-marker technique. Glucose irreversible-loss rates and the contribution of propionate to gluconeogenesis were measured using continuous infusions of [U-14C]glucose and [2-14C]propionate. 3. Amino acid flow into the duodenum was significantly (P less than 0.01) increased from 238 g/d on the control treatment to 319 g/d on FM2, but there was no response to FM1 (P greater than 0.05). 4. Glucose irreversible loss rate remained constant with an average value of 1.86 mg/min per kg LW. 5. Neither the percentage of glucose synthesized from propionate (average 30) nor the percentage of propionate converted to glucose (average 45) was significantly altered by treatment (P greater than 0.05).
Amino Acids↗
Merton Gill. Interview by Joseph Reppen.
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Humans↗