Biomedical subjects

C J Field

Publications and source records attributed to C J Field.

At least 55 records · Page 3Linked to original sources

PubMed1991

Enhanced 2-deoxy-D-glucose uptake and metabolism in splenocytes from diabetic and diabetes-prone BB rats. Further evidence to support prior in vivo activation.

Glucose metabolism in splenocytes from the BB rat was studied for the presence of abnormalities in [14C] 2-deoxy-D-glucose (2-dGlc) uptake, [U-14C]glucose conversion to 14CO2, and the production of lactate and pyruvate. Cells were studied freshly isolated ("resting"), and following culture both unstimulated (control) and stimulated with concanavalin A (ConA) or phorbol myristate acetate (PMA) + ionomycin. Both resting and control cells from diabetic (BBd) and diabetes-prone (BBdp) rats transported more (p less than 0.05) 2-dGlc than did cells from nondiabetes-prone (BBn) rats. Consistent with prior in vivo activation, sustained in vitro, lactate production was higher (p less than 0.05) under control conditions in BBd and BBdp than in BBn cells. Lactate production increased less with ConA and PMA + ionomycin in both BBd and BBdp than in BBn cells. PMA + ionomycin increased 2-dGlc uptake as much in BBd and BBdp cells as in BBn cells. Elevated rates of pyruvate production were observed in BBd cells under resting, control, and (especially) ConA conditions, suggesting an abnormality in pyruvate conversion to lactate. Few changes were observed in 14CO2 production. The presence of similar abnormalities in BBdp cells to those of the BBd cells suggests that the diabetic state is not causal, and the absence of an in vitro effect of 15 mmol/liter glucose in BBn cells further tends to exclude hyperglycemia as a cause of these alterations.

Animals↗

PubMed1991

Elevated glutamine metabolism in splenocytes from spontaneously diabetic BB rats.

To investigate the metabolic fates of glutamine in splenocytes from the BB rat with spontaneous immunologically mediated insulin-dependent diabetes, freshly isolated cells were incubated in Krebs-Ringer Hepes buffer with 1.0 mM-[U-14C]glutamine and 0, 4 mM- or 15 mM-glucose. (1) The major products of glutamine metabolism in splenocytes from normal and diabetic rats were ammonia, glutamate, aspartate and CO2. (2) The addition of glucose increased (P less than 0.01) glutamate production, but decreased (P less than 0.01) aspartate and CO2 production from glutamine, as compared with the values obtained in the absence of glucose. However, there were no differences in these metabolites of glutamine at 4 mM- and 15 mM-glucose. (3) At all glucose concentrations used, the productions of ammonia, glutamate, aspartate and CO2 from glutamine were all markedly increased (P less than 0.01) in splenocytes from diabetic rats. (4) Potential ATP production from glutamine in the splenocytes was similar to that from glucose, and was increased in cells from the diabetic rat. (5) ATP concentrations were increased (P less than 0.01) in diabetic-rat splenocytes in the presence of glutamine with or without glucose. (6) Our results demonstrate that glutamine is an important energy substrate for splenocytes and suggest that the increased glutamine metabolism may be associated with the activation of certain subsets of splenocytes in the immunologically mediated diabetic syndrome.

Adenosine Triphosphate↗

PubMed1991

Changes in circulating leukocytes and mitogen responses during very-low-energy all-protein reducing diets.

Chronic and acute protein-energy malnutrition impairs immune function but little is known of the effects of energy deprivation alone. Indexes of cell-mediated immunity (CMI) were therefore studied during a 6-wk very-low-energy diet (VLED) (1.7 MJ/d, weight loss 13 +/- 1 kg, means +/- SEM) in 12 nondiabetic obese [body mass index 33 +/- 1 (in kg/m2)] subjects. Significant decreases (P less than 0.05) were observed in the numbers of total leukocytes, neutrophils, lymphocytes, and monocytes from 1 to 2 wk of the VLED and onward. Only lymphocyte counts returned to baseline levels with refeeding. The proportions of other monoclonal-antibody-defined mononuclear cell populations (except a small decrease in CD4+) did not change during dieting. [3H]Thymidine uptake by mononuclear cells cultured for 96 h decreased significantly (P less than 0.05) at wk 6 in response to concanavalin A, phytohemagglutinin, and pokeweed mitogen and after only 1 wk to phorbol myristate acetate + ionomycin. Delayed-type-hypersensitivity skin-test responses did not decrease at wk 5 vs those at baseline. The VLED produced nonspecific decreases in circulating leukocyte numbers and in vitro responses to several mitogens (of different cell-subset specificity), suggesting that in susceptible individuals or if there is longer exposure to such diets, such responses could assume clinical significance.

Adult↗

PubMed1991

Dietary fat: exogenous determination of membrane structure and cell function.

Evidence indicates that principal features of the membrane involve structural organization of lipids in the form of a bilayer with functional proteins either bound to the bilayer surface or inserted into the bilayer and interacting within specific domains in the lipid milieux. In homeotherms, intrinsic and extrinsic factors apparently form the basis for determination of membrane lipid composition and thus membrane physicochemical properties. Moreover, many intrinsic metabolic controls, such as fatty acid desaturation and phospholipid biosynthesis, may be attenuated by change in the nature of the extrinsic or dietary influence. This review will focus on the role of dietary fat as a determinant of subcellular structural constituents to illustrate that feeding nutritionally adequate diets differing in fatty acid composition can induce physiological transitions in membrane function involving the activity of enzymes responsible for synthesis of membrane constituents, hormone-activated functions and expression of activity in the cell nucleus.

Animals↗

PubMed1991

Glutamine and glucose metabolism in thymocytes from normal and spontaneously diabetic BB rats.

Metabolism of glutamine and glucose was studied in thymocytes from normal rats and BB rats with the spontaneous autoimmune diabetic syndrome to assess their potential roles as fuels. The major measured products from glucose were lactate and, to a lesser extent, CO2, and pyruvate. Glutamine had no effect on the rates of their production from glucose. Glutamine was metabolized to ammonia, aspartate, glutamate, and CO2, with aspartate being the major product of carbons from glutamine in the absence of glucose. Glucose markedly decreased the formation of ammonia, aspartate, and CO2 from glutamine, but increased that of glutamate, with an overall decrease in glutamine utilization by 55%. More glutamate than aspartate was produced from glutamine in the presence of glucose. The potential production of ATP from glucose was similar to that when glutamine was present alone. However, glucose markedly decreased production of ATP from glutamine, but not vice versa. This resulted in ATP production from glucose being 2.5 times that from glutamine when both substrates were present. The oxidation of glucose to CO2 via the Krebs cycle accounts for 75-80% of glucose-derived ATP production. Cellular ATP levels markedly decreased in the absence of exogenous substrates, but were constant throughout a 2-h incubation in the presence of glutamine, glucose, or both. There were no differences in thymocyte glucose or glutamine metabolism between normal and diabetic BB rats, in contrast to previous findings in peripheral lymphoid organs. Our results suggest that glucose is a more important fuel than glutamine for "resting" thymocytes, again in contrast to the cells of peripheral lymphoid organs in which glutamine is as important as glucose as a fuel.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1991

Glutamine and glucose metabolism in rat splenocytes and mesenteric lymph node lymphocytes.

The metabolism of glutamine (2 mM) and glucose (5 mM) was studied in splenocytes and mesenteric lymph node lymphocytes of Wistar-Furth rats to assess their relative importance as energy substrates. The major products from glutamine were ammonia, glutamate, aspartate, and CO2, whereas those from glucose were lactate, pyruvate, and CO2 in cells from both lymphoid organs. The individual rates of glutamine and glucose metabolism were decreased in the presence of both substrates, compared with the rates when present separately. The rates of glucose and some (but not all) aspects of glutamine metabolism were higher (P less than 0.01) in splenocytes than in mesenteric lymphocytes. In cells from both lymphoid organs, glutamine and glucose could potentially contribute almost equal amounts of ATP in the presence of both substrates. Glutamine and glucose individually were able to provide sufficient amounts of ATP to maintain its concentrations in the cells throughout a 2-h incubation period at the same levels as with both substrates present. We also found that splenocyte concentration (3.3-100 x 10(6) cells/ml) in the incubations is an important determinant of rates of metabolite formation from glutamine when expressed per 10(6) cells. We conclude that glucose is not the only quantitatively significant energy substrate or even the major one for lymphocytes, because glutamine at near-physiological concentration can be readily utilized by these cells.

Adenosine Triphosphate↗

PubMed1991

Circulating mononuclear cell numbers and function during intense exercise and recovery.

To investigate the effect of intense exercise on immune function, 12 healthy males (26 +/- 1 yr) underwent cycle exercise to exhaustion at 80% maximum work load. One hour later, six of the subjects underwent a second identical bout. Blood was drawn preexercise (C), at exhaustion (Ex-1, Ex-2), and at 1 h of recovery (Rec-1, Rec-2). At Ex-1 and Ex-2, total leukocytes (monocytes, neutrophils, and lymphocytes) increased significantly (P less than 0.05), and all returned to C levels by Rec-1 except lymphocytes, which were lower than at C. At Rec-2 total leukocytes remained higher (P less than 0.05) than at C, primarily because of elevated neutrophil counts. Phenotype analysis indicated a 2.5-fold increase in CD16+ (natural killer) cells at Ex-1 and a decrease primarily in CD4+ (T-helper) cells. All phenotype changes returned to C levels at Rec-1. At Ex-1 the in vitro mitogenic response to concanavalin A, phorbol myristate acetate + ionomycin, phytohemagglutinin, and pokeweed mitogen decreased (P less than 0.05) but returned to levels not different from C at Rec-1. Both the in vitro percent specific lysis of a target natural killer cell (K562) and the lytic activity per cell increased (P less than 0.05) in peripheral mononuclear cells at Ex-1, returning to C levels at Rec-1. The total leukocyte counts with exercise were significantly correlated with plasma epinephrine concentration, and a causal effect is thus possible. Such acute changes in numbers and function of circulating cells of the immune system may possibly have functional and clinical correlates.

Adult↗

PubMed1991

Glucoregulatory and hormonal responses to repeated bouts of intense exercise in normal male subjects.

Glucose turnover and its regulation were studied during and after two identical bouts of intense exhaustive exercise separated by 1 h to define differences in response. Six lean young postabsorptive male subjects exercised at approximately 100% maximal O2 uptake (3.7 +/- 0.3 l/min) for 13.0 +/- 0.7 min for the first (EX1) and 13.2 +/- 0.8 min for the second (EX2) bout. Plasma glucose increased during EX1 and peaked at 7.0 +/- 0.6 mmol/l in early recovery but to 5.8 +/- 0.5 mmol/l (P less than 0.05) after EX2, and both the hyperglycemic and the hyperinsulinemic responses were less after EX2 (P less than 0.015, analysis of variance). The hyperglycemia was due to lesser increments in glucose utilization (Rd) (3-fold resting) than glucose production (Ra) (7-fold) toward exhaustion and for 7 min of recovery. The rise in Rd was more rapid (P less than 0.05) and metabolic clearance rate was greater during (P = 0.015) and from 9 to 60 min after EX2, and Ra also remained higher during recovery (P less than 0.05). Marked and similar increments in plasma norepinephrine (18-fold) and epinephrine (14-fold) occurred with both bouts. Plasma glucagon increments were small and not different. Therefore, 1) more circulating glucose was used with EX2, 2) greater metabolic clearance rate during and after EX2 suggests local muscle adaptations due to EX1, and 3) significant correlations (P less than 0.002) between plasma norepinephrine and Ra (r = 0.82) and Ra - Rd (r = 0.52) and between epinephrine and Ra (r = 0.71) and Ra - Rd (r = 0.48) suggest a major regulatory role for the catecholamine responses.

Adult↗

PubMed1990

Lactate production is the major metabolic fate of glucose in splenocytes and is altered in spontaneously diabetic BB rats.

Enhanced glucose metabolism is necessary to support the activation and proliferation of lymphocytes. To define further quantitatively the metabolic fates of glucose and assess glucose utilization both in normal cells and in an autoimmune disease with abnormal lymphocytes, [U-14C]glucose conversion into 14CO2 and the production of lactate and pyruvate were measured in splenocytes. Cells from non-diabetes-prone (BBn) and spontaneously diabetic (BBd) rats were studied both freshly isolated 'resting' and cultured for 96 h with and without concanavalin A (Con A) stimulation. (1) Lactate was confirmed to be the major end product in both freshly isolated (53% of utilized glucose) and unstimulated cultured (62% of utilized glucose) cells from BBn animals studied at (2-8) x 10(6) cells/ml concentration. The use of concentrations from 10 x 10(6) to 300 x 10(6) cells/ml resulted in progressively less lactate production per 10(6) splenocytes. (2) Cells from BBd animals after stimulation with Con A incorporated less [3H]thymidine and produced significantly less lactate (155 +/- 14 versus 305 +/- 24 nmol/2 h per 10(6) cells) than did BBn cells (P less than 0.05). (3) However, more lactate (101 +/- 8 versus 78 +/- 6 nmol/5 h per 10(6) cells) was produced by 'resting' cells from BBd animals compared with BBn (P less than 0.03), and this difference was sustained after 4 days in culture. (4) Significantly greater amounts of pyruvate were produced by BBd than by BBn cells, particularly when stimulated with Con A, suggesting an alteration in the availability of reducing equivalents in BBd cells. (5) These results are consistent with prior metabolic as well as immunological 'activation' of cells in vivo in the BB diabetic animals.

Adenosine Triphosphate↗

PubMed1990

Diet fat composition alters membrane phospholipid composition, insulin binding, and glucose metabolism in adipocytes from control and diabetic animals.

The present study was designed to determine if diet fat-induced alteration in the fatty acid composition of the adipocyte plasma membrane alters insulin binding and the insulin responsiveness of glucose metabolism in control and diabetic states. Normal (control) and diabetic (streptozotocin-induced) rats were fed high fat semipurified diets providing a high or low polyunsaturated to saturated fatty acid (P/S) ratio. Feeding a high P/S diet increased the polyunsaturated fatty acid content of major membrane phospholipids of the adipocyte plasma membrane from both normal and diabetic animals. The diabetic state was associated with an elevated content of linoleic acid and a reduced level of arachidonic acid consistent with reduced delta 6-desaturation. Feeding the high P/S diet to diabetic animals increased membrane linoleic acid content and prevented the decrease observed in the arachidonic acid of membrane phospholipids. The high P/S diet was associated with increased insulin binding in nondiabetic animals but did not change the amount of insulin bound by cells from diabetic animals. Significantly (p less than 0.05) increased rates of insulin-stimulated glucose transport and lipogenesis (glucose incorporation into lipids) were observed in control animals fed the high as compared to the low P/S diet. The rates of insulin-stimulated glucose transport, oxidation, and lipogenesis were lower (p less than 0.05) for cells from diabetic as compared to control animals. However, feeding a high P/S diet significantly improved rates for all three of these functions (p less than 0.05). It is concluded that diet-induced alterations in membrane composition may provide a mechanism for improving the cellular response to insulin in cells from diabetic animals.

Adipose Tissue↗

PubMed1989

Relationship between dietary fat, adipocyte membrane composition and insulin binding in the rat.

Weanling male Sprague-Dawley rats were fed one of 10 purified, high fat (20% wt/wt) diets for 6 wk to determine if an in vivo relationship exists between dietary fat composition, plasma membrane composition and insulin binding to epididymal adipocytes. The diets fed provided ratios of polyunsaturated to saturated fatty acids (P/S ratios) representative of those consumed by the human population and ranging from 0.14 to 1.80. The dietary P/S ratio fed altered the essential and nonessential fatty acid composition of plasma membrane phospholipids. Diet-induced alterations in membrane phosphatidylcholine and phosphatidylethanolamine composition were found to be related in a dose-dependent manner to insulin binding at both physiological and supraphysiological insulin concentrations. This observation further supports in vivo a dietary mechanism for modulating insulin action. The present study establishes that the effect of diet on the relationship between membrane composition and insulin binding reaches a plateau within the physiological range of dietary P/S ratios.

Adipose Tissue↗

PubMed1989

The effect of dietary fat content and composition on adipocyte lipids in normal and diabetic states.

Cellular insulin resistance is a common feature of the diabetic and obese state. To determine the effect of dietary fat and the insulin resistant state of diabetes on adipose tissue composition, control and streptozotocin-induced diabetic rats were fed four diets differing in fat content (10 percent w/w or 20% w/w) and polyunsaturated to saturated fatty acid (P/S) ratios (0.2 or 2.0) for 6 weeks. At 3 weeks diabetes was induced in half the animals in each diet group. Increasing the fat content and P/S ratio of the diet increased the content of polyunsaturated fatty acids and decreased the contents of monounsaturated and omega-3 fatty acids. The higher level of C-18:2(6) and the lower levels of C20:4(6) and monounsaturated fatty acids observed in diabetic animals is consistent with altered desaturase enzyme activity. Diet and diabetes induced compositional changes in essential and non-essential fatty acids in the adipose tissue may alter the total body pools of available fatty acids for the synthesis of other lipids such as phospholipids.

Adipose Tissue↗

PubMed1988

Dietary fat and the diabetic state alter insulin binding and the fatty acyl composition of the adipocyte plasma membrane.

Control and diabetic rats were fed on semi-purified high-fat diets providing a polyunsaturated/saturated fatty acid ratio (P/S) of 1.0 or 0.25, to examine the effect of diet on the fatty acid composition of major phospholipids of the adipocyte plasma membrane. Feeding the high-P/S diet (P/S = 1.0) compared with the low-P/S diet (P/S = 0.25) increased the content of polyunsaturated fatty acids in membrane phospholipids in both control and diabetic animals. The diabetic state decreased the content of polyunsaturated fatty acids, particularly arachidonic acid, in adipocyte membrane phospholipids. The decrease in arachidonic acid in membrane phospholipids of diabetic animals tended to be normalized to within the control values when high-P/S diets were given. For control animals, altered plasma-membrane composition was associated with change in insulin binding, suggesting that change in plasma-membrane composition may have physiological consequences for insulin-stimulated functions in the adipocyte.

Adipose Tissue↗

PubMed1986

A single-subject study of imipramine in a mentally retarded woman with depressive symptoms.

A double-blind, placebo-controlled, reversal design was used to assess imipramine. The subject was a young woman, with moderate mental retardation, whose salient clinical characteristics included weight loss, episodes of screaming and crying, agitation, and generally high levels of irritable behaviour. As compared with placebo, 100 mg of imipramine resulted in consistent improvement in terms of increased food consumption, decreases in screaming and crying, and stabilized sleep. Drug effects were fairly specific and a number of other clinical variables were unaffected by treatment. There was no evidence that imipramine impaired cognitive functioning as assessed by IQ performance.

Adult↗

PubMed1986

Prevalence of toxic anticonvulsant drug concentrations in mentally retarded persons with epilepsy.

Anticonvulsant drug concentrations in retarded individuals (117 hospital residents, 58 community-based) were surveyed. Concentrations of carbamazepine (CBZ, Tegretol) and phenytoin (Dilantin) were determined in salivary samples collected before morning medication (premedication sample) and 4 hours later (postmedication sample). Of 146 individuals receiving CBZ, 16% had salivary concentrations above the therapeutic range on at least one sample, whereas 2% exceeded the range on both samples. Of the 54 subjects prescribed phenytoin, 28% had at least one salivary concentration exceeding the therapeutic range, and 15% surpassed the therapeutic range on both samples. These data suggest the desirability of using regular therapeutic drug monitoring and neurological assessments to avoid the possibility of toxic drug levels in this population. A variety of subject and pharmacological variables (sex, severity of retardation, number of seizures in the last year, and dose) were also examined for their relationship to drug concentrations.

Adult↗

PubMed1985

City-wide survey of drug patterns among non-institutionalized mentally retarded persons.

This was a survey of 1,012 non-institutionalized mentally retarded persons living in a medium-sized metropolitan area. The sample was drawn from special schools and two service agencies in Auckland that serve preschool and adult retarded people. These are the main organizations serving this population in Auckland, and collectively they include a large proportion of non-institutionalized retarded individuals in this city. A comprehensive summary of current medication was obtained for each subject. A variety of demographic, medical, social, and sleep data were collected and, where appropriate, information was gathered regarding time elapsed since the last seizure. Two percent of preschoolers, 3% of special school students, and 14% of adults were receiving psychotropic drugs. Anticonvulsant drugs were prescribed for 31% of preschoolers, 17% of special school cases, and 18% of the adults. A large proportion of the demographic, medical, and social/sleep variables were associated with drug prescription patterns. These factors were discussed with respect to other surveys, and possible explanations were offered to account for their relationship to pharmacotherapy.

Adolescent↗

PubMed1985

Relationship of diet to the fatty acid composition of human adipose tissue structural and stored lipids.

The habitual intake of 20 healthy free-living subjects was determined by two 7-day food records. Documented fatty acid intakes were utilized to examine the influence of fatty acid intake on fatty acid composition of stored and structural lipids in subcutaneous adipose tissue. Subjects with higher intakes of saturated fatty acids exhibited increased levels of total saturated fatty acids and decreased polyunsaturated fatty acids in adipose tissue triglycerides (p less than 0.01). The dietary P/S ratio was significantly related to the saturated and polyunsaturated content of stored lipids. In the phospholipid fraction, relationships were found between dietary C18:2(6) and the P/S ratio of phosphatidylcholine (p less than 0.05). The essential fatty acid content of the two phospholipids studied was related to the dietary fats consumed. Relationships were identified between major fatty acids in the triglyceride and phospholipid fraction. Although diet was found to relate to fatty acid composition, the structural lipids in human adipose tissue appear more resistant to compositional change than stored triglycerides.

Adipose Tissue↗

PubMed1985

Role of diet fat in subcellular structure and function.

Current concepts of the biomembrane will be extrapolated to membranes of homeotherms to illustrate the influence of the nature of dietary lipid in nutritionally complete diets on membrane polar head group content and fatty acid composition. Utilizing animal models, the controlling influence of dietary long chain fatty acids on major lipid constituents of the mitochondrial membrane in cardiac tissue, the plasma membrane of liver, and the synaptosomal membrane in brain can be demonstrated. Diet-induced alterations in membrane composition are associated with demonstrable changes in the function of specific membrane proteins. To illustrate this relationship, the effect of diet on mitochondrial ATPase activity and on a hormone receptor-stimulated function in the plasma membrane of the liver will be discussed. These observations suggest that the diet fat modulates enzyme functions in vivo by changing the surrounding lipid environment in the membrane.

Adenosine Triphosphatases↗