Search PubMed⌕ Search

Biomedical subjects

R T Holman

Publications and source records attributed to R T Holman.

At least 37 records · Page 2Linked to original sources
PubMed1991

Obesity and weight loss alter serum polyunsaturated lipids in humans.

Serum omega 6 (n-6) fatty acids were assessed in 12 obese women during an outpatient very-low-calorie diet (VLCD). Ten subjects (S10) achieved a mean weight loss of 17 kg over 3-5 mo (initial weight-for-height 157%). Serum was obtained before (baseline) and monthly during the VLCD and from five of them (S5) after 2-3 mo of weight stability (refed) at 21 kg of loss. At baseline for S10, the serum phospholipid (PL) 20:4 omega 6 was 9.16 wt% and differed from normal (12.81 wt%) by P less than 0.0001, but cholesterol ester (CE) 20:4 omega 6 did not differ from normal. During 3 mo of VLCD, the S10 serum PL and CE 18:2 omega 6 fell (P less than 0.005 and 0.0001, respectively). Serum PL 20:4 omega 6 rose to normal during VLCD months 1-3 (P less than 0.01) while the serum CE 20:4 omega 6 rose above normal (P less than 0.0002). During the VLCD, S5 results paralleled S10. However when refed, S5 PL and CE 18:2 omega 6 and 20:4 omega 6 all reverted to baseline (PL 20:4 omega 6 below normal, P less than 0.001). Serum PL 20:4 omega 6 is low in moderate obesity, corrects to normal during a VLCD, but regresses to the predict abnormality after weight loss.

Adult↗
PubMed1991

Essential fatty acid status and fluidity of plasma phospholipids in cystic fibrosis infants.

The fatty acid (FA) patterns of cord serum phospholipids (PLs) were examined in 4 cystic fibrosis (CF) newborns, 8 non-CF siblings, and 22 normal control subjects. Plasma from 27 newly diagnosed CF infants and 38 normal infants aged less than 2 y were studied for comparison. CF cord-blood PLs had patterns similar to those of CF siblings and to normal newborns, but the pattern for CF did not shift toward adult patterns during infancy as did patterns for normal infants. CF infants at diagnosis exhibited a deficiency pattern in which 18: 2 omega 6, 20:4 omega 6, 22:4 omega 6, an omega 3 polyunsaturated fatty acids (PUFAs) were significantly subnormal and 18:3 omega 6, total saturated fatty acids, and total monounsaturated fatty acids were significantly elevated compared with normal infants. In PLs in CF infants, although mean chain length of FAs was low, mean melting point was elevated 2.4 degrees C and double-bond index was low (both P less than 0.001), implying a significantly lessened fluidity. Nutritional supplements of both omega 6 and omega 3 PUFAs are cated.

Aging↗
PubMed1991

Omega 3 polyunsaturated fatty acids as modulators of cellular function in the critically ill.

Continued improvement in outcome in ICU patients with the hypermetabolism-organ failure syndrome require a better understanding of the disease process. Current research is focusing on altered regulation at the cell membrane and nuclear levels. Cell culture models have provided insight into one possible mechanism, that of altered cell-cell communication with dysregulation of the associated parenchyma. Alteration of the PUFA content of the membrane of macrophages with omega 3 PUFA can be easily induced and maintained, and can alter cell membrane physical characteristics and how the membrane responds to LPS-stimulated prostanoid release. There is also an associated alteration in the release of monokine. These changes are associated with improvements in T lymphocyte response to antigen and in outcome from septic peritonitis. The precise mechanisms through which these effects occur are the subject of investigations, as are the clinical implications. Nonetheless, nutrient pharmacology with omega 3 PUFA may be a promising area of research that will have clinical applicability in ICU patients.

Cell Membrane↗
PubMed1990

Alteration of the cellular fatty acid profile and the production of eicosanoids in human monocytes by gamma-linolenic acid.

We administered borage seed oil (9 capsules/day) for 12 weeks to 7 normal controls and to 7 patients with active rheumatoid arthritis. The therapy provided 1.1 gm/day of gamma-linolenic acid (GLA). GLA administration resulted in increased proportions of its first metabolite, dihomo-gamma-linolenic acid (DGLA), in circulating mononuclear cells. The ratios of DGLA to arachidonic acid and DGLA to stearic acid increased significantly in these cells. Significant reductions in prostaglandin E2, leukotriene B4, and leukotriene C4 produced by stimulated monocytes were seen after 12 weeks of GLA supplementation. The antiinflammatory effects of GLA administration observed in animal models, and the apparent clinical improvement experienced by 6 or 7 rheumatoid arthritis patients given borage seed oil in this open, uncontrolled study may be due in part to reduced generation of arachidonic acid oxygenation products.

Administration, Oral↗
PubMed1990

Reduced adipose 18:3 omega 3 with weight loss by very low calorie dieting.

The human undergoing rapid and sustained weight loss by very low calorie dieting (VLCD) derives the majority of daily energy needs from adipose fatty acids. To evaluate the rates of metabolic utilization of individual fatty acids in humans, two groups of adult women outpatients were studied during major weight loss by VLCD. The diets used were either food or formula, providing the recommended dietary allowance for minerals and vitamins, with fat contents of 2-20 g/d. Group 1 consisted of 10 subjects [initial body mass index (BMI) 32.7, 157% of ideal body weight (IBW)] with a mean loss of 17.7 kg in 3-5 months. Group 2 consisted of 14 subjects (initial BMI 36.7, 167% of IBW) with a mean loss of 25.6 kg in 4-5 months. Adipose tissue biopsies were obtained by needle aspiration from Group 1 before and after weight loss and from Group 2 before, at the midpoint, and after weight loss. With weight loss in Group 1, the adipose tissue content of 18:1 omega 9, 18:2 omega 6, and 20:4 omega 6 did not change, but 18:3 omega 3 fell (0.67 to 0.56 wt%, p less than 0.0001) as did 20:5 omega 3 (0.08 to 0.05, p less than 0.01). Adipose tissue 22:6 omega 3 rose from 0.03 to 0.07 (p less than 0.01). In Group 2, only 18:3 omega 3 showed a change, falling from 0.71 to 0.69 to 0.59 wt% across weight loss (p = 0.03 by analysis of variance). We conclude that the major fatty acids are oxidized in proportion to their composition in adipose triglyceride.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1990

Influence of hyperalimentation on rat hepatic microsomal fluidity and function.

Total parenteral nutrition with an amino acid-glucose solution has previously been shown to decrease rat hepatic drug metabolism compared with drug metabolic activity observed in rats receiving the same solution enterally and chow-fed animals. Because changes in membrane fluidity and lipid composition are reported to influence activity of a number of liver enzymes, effects of parenteral and enteral nutrition on hepatic microsomal membrane fluidity and lipid composition were assessed and compared with hepatic mixed-function oxidase activity. Both parenteral and enteral hyperalimentation produced a significant decrease in microsomal membrane fluidity (fluorescence anisotropy = 0.155 +/- 0.003 in both experimental groups versus 0.129 +/- 0.003 for microsomes from chow-fed animals). However, meperidine demethylase activity was significantly decreased compared with chow-fed experiments only in hepatic microsomes from parenterally hyperalimented animals, whereas ethoxyresorufin deethylase activity was significantly reduced only in the enteral-nutrition group. Inclusion of lipid in the parenterally administered hyperalimentation solution normalized microsomal membrane fluidity and lipid profile to those of chow-fed animals but did not increase hepatic meperidine demethylation. Both parenteral and enteral nutrition produce significant changes in physical state and lipid composition of rat hepatic microsomal membranes, but these changes are not responsible for the altered hepatic drug metabolism observed during hyperalimentation.

Animals↗
PubMed1990

Reduced arachidonate in serum phospholipids and cholesteryl esters associated with vegetarian diets in humans.

Lipid fractions such as phospholipids (PLs), cholesteryl esters (CEs), and free fatty acids (FFAs) represent source pools for eicosanoid synthesis. To determine whether dietary habits affect the enrichment of 20:4n-6 in these precursor pools, we studied humans with partial or complete arachidonate restriction resulting from chronic avoidance of animal fat and tissue. Fasting serum was obtained from omnivorous control subjects (Omni, n = 100), semivegetarians (Semiveg, n = 16), and vegetarians (Veg, n = 25). PLs, CEs, FFAs, and triglyceride (TG) fatty acids were quantitated by thin-layer and gas chromatography. Serum 20:4n-6 was lower in the PL fraction in both Veg (p less than 0.01) and Semiveg groups (p less than 0.05) than in the Omni group and lower in the CE fraction in the Veg group (p less than 0.05). Serum 18:2n-6 did not differ between groups for any serum lipid fraction. 18:3n-3 was elevated in PLs and CEs of both Veg (p less than 0.05 and 0.01) and Semiveg groups (p less than 0.05 and 0.01) compared with the Omni group but did not result in differences in 20:5n-3 in PLs or CEs between diet groups. The lower concentration of 20:4n-6 in serum PLs and CEs of the Veg group indicates that dietary arachidonic acid enriches its circulating pool in humans; however, 20:5n-3 is not similarly responsive to dietary restriction.

Adult↗
PubMed1989

Modulation of hepatic ferrochelatase activity by dietary manipulation of mitochondrial phospholipid fatty acyl groups.

Ferrochelatase is an enzyme bound to the inner mitochondrial membrane, which is important in heme biosynthesis. Activity of purified ferrochelatase is affected by the presence of certain fatty acids. In the present study, we examined whether the activity of ferrochelatase is altered by dietary manipulation of the composition of mitochondrial membrane phospholipid fatty acyl groups. Rats were fed diets containing triolein, safflower or menhaden oil as 5% (w/w) of the diet. After 3 weeks, the animals were killed and liver mitochondria were isolated. Phospholipid fatty acid composition and ferrochelatase activity were assayed in the isolated mitochondria. Marked differences were seen. The proportion of oleic acid was highest in the triolein oil-fed group, that of linoleic and arachidonic acid was highest in the safflower oil-fed group and the proportion of eicosapentaenoic acid was highest in the menhaden oil-fed group. Ferrochelatase activity was greatest in the triolein oil-fed group and lowest in the menhaden oil-fed group regardless of whether the mitochondria were intact, sonicated or sonicated and treated with Tween 20. Mixing of mitochondria from menhaden oil-fed rats with triolein oil resulted in a significant increase in ferrochelatase activity. Membrane fluidity and activities of the mitochondrial membrane enzymes succinic dehydrogenase and cytochrome oxidase did not differ among the groups. We conclude that dietary manipulation of mitochondrial membrane phospholipid fatty acyl group composition can directly modulate hepatic ferrochelatase activity. This has potential application in the treatment of protoporphyria, the genetic disorder in which ferrochelatase activity is deficient.

Animals↗
PubMed1989

Fatty acid pattern of tissue phospholipids in copper and iron deficiencies.

Because copper and iron have been reported to be essential cofactors in delta 9 desaturation of fatty acids, the effects of different dietary intakes of copper and iron on tissue fatty acids were studied. Male Long-Evans rats (ten per group) were fed diets containing adequate, deficient or excess copper or iron. On day 42 of the dietary regimen, the animals were killed and tissues and blood were removed for analysis of metals and fatty acids of phospholipids. Compared with the copper-adequate rats, the copper-deficient rats showed increased 18:0 in liver and decreased 16:1 omega 7 in liver, heart and serum. There were no differences for 16:0 or 18:1 omega 9. Intake of excess copper did not cause an increase in products of delta 9 desaturation. Comparisons between iron-deficient and iron-adequate rats showed that iron deficiency increased 18:2 omega 6 in liver and serum and decreased 20:4 omega 6 in serum only. Relative percentages of 16:0, 18:0, 16:1 omega 7 and 18:1 omega 9 in liver and serum phospholipids were similar for both groups. Intake of excess iron caused a decrease in 18:2 omega 6; and 16:0 and 18:1 omega 9 were higher in the liver of the iron-excess group than the iron-deficient group. This study did not support the requirement for copper or iron in the delta 9 desaturation of fatty acids as expressed in phospholipids of liver, heart and serum.

Animals↗
PubMed1989

Modulation of Kupffer cell membrane phospholipid function by n-3 polyunsaturated fatty acids.

Dietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to improve clinical outcome in a number of inflammatory diseases including burns and sepsis. One mechanism contributing to the anti-inflammatory effect is the incorporation of n-3 PUFAs into membrane phospholipids which decreases macrophage eicosanoid production. We hypothesize that an additional mechanism for their effects is an alteration of membrane signal transduction that decreases macrophage responsiveness to inflammatory stimuli. Kupffer cells, the fixed macrophages of the liver, were obtained from rats pair fed diets for 6 weeks with 15% of calories supplied as menhaden (high n-3), corn (control), or safflower (high n-6) oils. The effects of the dietary oils on Kupffer cell membrane signal transduction and eicosanoid production were assessed by measuring inositol phospholipid (PI) metabolism, intracellular calcium responses, and prostaglandin E2 (PGE2) production to the inflammatory signals endotoxin (LPS) and platelet activating factor (PAF). The menhaden oil diet resulted in significant incorporation of n-3 PUFAs into total cellular PUFAs compared to corn and safflower oil. (total n-3 PUFAs, 28.1% menhaden vs 2.1% corn vs 1.2% safflower, P less than 0.03). This incorporation altered signal transduction of PAF as both PI turnover (65% +/- 10% of corn oil) and calcium response (0.6-fold vs 5.0-fold for corn oil) were significantly reduced in the menhaden oil group. (P less than 0.05) The menhaden oil diet also reduced significantly PGE2 production in response to PAF and LPS (corn, 348 +/- 23 pg/ml; menhaden, 48 +/- 6 pg/ml, P less than 0.01). We conclude that, in addition to modulating eicosanoid production, n-3 PUFAs can also alter macrophage membrane signal transduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Deficiencies of polyunsaturated fatty acids and replacement by nonessential fatty acids in plasma lipids in multiple sclerosis.

Fatty acid compositions of plasma phospholipids, cholesteryl esters, triacylglycerols, and nonesterified fatty acids of 14 clinically proven and graded cases of multiple sclerosis were determined by capillary gas chromatography and compared with the values obtained for 100 normal, healthy subjects. In phospholipids, linoleic acid (18:2 omega 6; 18 carbon atoms, 2 double bonds, 6 carbon atoms beyond last double bond) was normal and 18:3 omega 6 was increased, but all subsequent omega 6 acids were subnormal (P less than 0.001), indicating impairment of chain elongation. All omega 3 acids were subnormal. The paucity of polyunsaturated fatty acids was compensated mass-wise by an increase in saturated acids. Disproportionate increases in short-chain, saturated, and monounsaturated acids, decreases in long-chain homologs, and increases of branched and odd-chain acids were observed. Loss of polyunsaturated fatty acids and replacement by nonessential acids lowered mean chain length and raised mean melting point significantly, suggesting that lowered membrane fluidity was only partially compensated by endogenous synthesis of lower-melting, nonessential acids. This phenomenon was not observed in cholesteryl esters or triacylglycerols. Nonesterified fatty acids showed significant changes in pattern of possible autacoid precursors. The abnormal profile of fatty acids in multiple sclerosis has features in common with profiles of other syndromes involving viral infections.

Adult↗
PubMed1989

Role of monokines in altering hepatic metabolism in sepsis.

Multiple organ failure continues to be the primary cause of death after trauma and sepsis. This clinical syndrome represents the transition from a hypermetabolic response to injury to a syndrome of progressive organ failures and death. Risk factors include: perfusion deficits, persistent foci of dead or injured tissue, an uncontrolled focus of infection, the presence of the respiratory distress syndrome, persistent hypermetabolism, and preexisting fibrotic liver disease. Once initiated, most treatment modalities for the organ failure syndrome become progressively ineffective including: ventilation, antibiotics, nutrition, and surgery. The best treatment remains prevention and rapid control of risk factors including restoration of oxygen transport and aggressive nutrition support. There seems to be no treatment "magic bullet" either experimentally or clinically once the syndrome has occurred. The metabolic response to injury involves alterations in physiology and in the metabolism of carbohydrate, fat and amino acids. These changes seem to reflect the modulation of the end-organs by the mediator systems activated in response to the stress stimuli. The transition from hypermetabolism to organ failure appears to reflect the clinical appearance of liver failure. It is hypothesized that this liver failure may represent a state of regulatory dysfunction induced in large part by the activated hepatic macrophage, the Kupffer cell. The activation of these macrophages is hypothesized to represent the final stage of a series of stimulating events, eg. hypoxia, endotoxin, bacteria, and gut translocated toxins. The precise monokine(s) responsible are not yet completely characterized, although Interleukin-1 (IL-1) and tumor necrosis factor (TNF) appear to be involved as do prostaglandins (Pg) such as PgE2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Hepatic dysfunction in multiple systems organ failure as a manifestation of altered cell-cell interaction.

Multiple organ failure continues to be the primary cause of death after trauma and sepsis. This clinical syndrome follows shock and resusitation and the transition from a hypermetabolic response to a syndrome of progressive organ failures and death. Risk factors include: perfusion deficits, persistent foci of dead or injured tissue, an uncontrolled focus of infection, the presence of the respiratory distress syndrome, and preexisting fibrotic liver disease. The imitation of the syndrome represents the clinical manifestation of hepatic failure. It is hypothesized that this hepatic failure results from paracrine amplification with Kupffer cell induced hepatocyte cytotoxicity. The best treatment remains prevention and rapid control of risk factors including restoration of oxygen transport and aggressive nutrition support. There seems to be no treatment "magic bullet" either experimentally or clinically once the syndrome has occurred.

Animals↗
PubMed1988

Composition of mixed octadecadienoates via ozonolysis, chromatography and computer solution of linear equations.

An approach to the analysis of 55 possible nonconjugated positional isomers of octadecadienoic acid is described and tested with mixtures of individual synthetic methyl esters. In the first example, by ozonolysis a seven-component mixture consisting of cis,cis 5,12-, 6,10-, 6,11-, 6,12-, 7,12-, 8,12-, and 9,12-octadecadienoates was converted to aldehydes, aldehyde-esters and dialdehydes. These fragments were separated on a 50 m X 0.2 mm free fatty acid phase (FFAP) vitreous silica capillary column. Equations for an arbitrarily restricted 12 X 15 matrix of linear simultaneous equations and a computer solution of the matrix provided the composition of the initial methyl octadecadienoate mixture. The power and significance of this method became apparent with the observation that only two of the seven isomers in the known mixture were resolved as single peaks by state-of-the-art capillary gas chromatography, but all seven were identified and estimated with acceptable error by the ozonolysis-capillary gas chromatography-computer procedure. In a generalized approach to the analysis of the 55 possible nonconjugated isomers, a computer program selects the appropriate matrix of linear simultaneous equations based on the aldehyde data supplied by the analyst. Twenty of 21 combinations of seven isomeric esters taken five at a time have been analyzed to assess the efficiency of the method. To illustrate applicability at this stage of development, the method has been used to analyze the diene products of the hydrazine reduction of gamma-linolenic acid and the diene products from the biological desaturation of isomeric monoenes.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Gas↗
PubMed1988

Polyunsaturated fatty acids of serum lipids in myocardial infarction.

Two groups of volunteers had blood drawn for serum analysis of fatty acids. The first group was comprised of patients admitted to the hospital with possible myocardial infarction (MI). Blood was drawn at admission and at 12, 24 and 48 hr. These patients were subsequently divided into three groups, those with MI, those without (No MI) and those taking prostaglandin inhibitors (PGI), on the basis of the cardiac enzymes, electrocardiograms and clinical history. A fourth group of Normal nonstressed people was also drawn at 0, 12, 24 and 48 hr for comparison. Fatty acid composition of phospholipids (PL), nonesterified fatty acids (NEFA), triglycerides (TG) and cholesteryl esters (CE) was determined by capillary gas chromatography (GC), and comparisons were made between the MI, No MI, PGI and Normal groups. Total NEFA were significantly elevated in patients admitted for possible MI compared with Normals. Those patients with MI had marginally higher levels of NEFA than the No MI group at each sampling time, but this difference was not statistically significant. The MI, No MI and PGI groups had significantly different fatty acid patterns in NEFA with reduced percentages of arachidonic acid (AA) than controls. The fatty acid patterns in the four lipid classes showed few significant differences comparing the MI, No MI and PGI groups. The regular use of prostaglandin inhibitors before hospitalization for chest pain was associated with a reduced frequency of MI (p less than 0.002). NEFA levels, nonesterified AA levels and fatty acid patterns in this group did not differ from those patients not taking prostaglandin inhibitors.

Arachidonic Acid↗