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Biomedical subjects

J F Mead

Publications and source records attributed to J F Mead.

At least 19 recordsLinked to original sources
PubMed1990

Increased vitamin E content in the lung after ozone exposure: a possible mobilization in response to oxidative stress.

Vitamin E (vE) is a biological free radical scavenger capable of providing antioxidant protection depending upon its tissue content. In previous studies, we observed that vE increased significantly in rat lungs after oxidant exposure, and we postulated that vE may be mobilized to the lung from other body sites under oxidative stress. To test this hypothesis, we fed Long-Evans rats either a vE-supplemented or a vE-deficient diet, injected them intraperitoneally with 14C-labeled vE, and then exposed half of each group to 0.5 ppm ozone (O3) for 5 days. After exposure, we determined vE content and label retention in lungs, liver, kidney, heart, brain, plasma, and white adipose tissue. Tissue vE content of all tissues generally reflected the dietary level, but labeled vE retention in all tissues was inversely related to tissue content, possibly reflecting a saturation of existing vE receptor sites in supplemented rats. Following O3 exposure, lung vE content increased significantly in supplemented rats and decreased in deficient rats, but the decrease was not statistically significant, and vE content remained unchanged in all other tissues of both dietary groups. Retention of 14C-labeled vE increased in all tissues of O3-exposed rats of both dietary groups, except in vE-deficient adipose tissue and vE-supplemented brain, where it decreased, and plasma, where it did not change. The marked increases in lung vE content and labeled vE retention of O3-exposed vE-supplemented rats support our hypothesis that vE may be mobilized to the lung in response to oxidative stress, providing that the vitamin is sufficiently available in other body sites.

Animals↗
PubMed1989

Turnover and fate of plasma free fatty acids in briefly-fasted lymphoma-bearing mice.

Body fat loss during tumor growth may be due to increased mobilization of adipose triglycerides. Earlier work from this laboratory suggested that (i) lymphoma-bearing AKR mice have a circulating lipid mobilizing factor (LMF) which caused body fat loss during cancer growth; that (ii) fatty acids (FA) mobilized in these tumor-bearing (TB) mice were not oxidized to CO2 as in starved mice that lose their body fat; and that (iii) instead, the mobilized FA were sequestered by the lymphoma. We tested these hypotheses by injecting [1-14C]palmitate-albumin into lymphoma-bearing and control mice. We measured turnover of plasma FFA for 24 hr and predicted the cumulative conversion of tracer into breath 14CO2 (at 85 min) in the TB mice. Plasma FFA were mobilized more slowly in briefly fasted tumor-bearing mice than in controls with the same plasma FFA pool sizes. The fractional catabolic rate (FCR) (min-1) of plasma FFA turnover in both groups decreased during the night when the mice ate: postabsorptive controls, 1.07 (+/- 5.6%); fed controls, 0.25 (+/- 13%); postabsorptive TB, 0.53 (+/- 4.6%); fed TB, 0.29 (+/- 7.3%). Virtually all of the plasma FFA irreversible disposal in TB mice was accounted for as breath 14CO2 (30 to 40% I.D.), not as tumor lipids (1.1 +/- 0.22% I.D.). Thus, FFA oxidation to CO2 is the major fate of plasma FFA turnover in TB mice, and sequestration of FFA (palmitate) by tumor cells is a quantitatively minor process. The putative circulating LMF did not cause increased FFA mobilization in these lymphoma-bearing mice in the post-absorptive state.

Animals↗
PubMed1988

Small hydrocarbons formed by the peroxidation of squalene.

Experiments were undertaken to determine whether peroxidized squalene forms isoprene in a manner such that peroxidation could be considered as a possible route for the formation of in vivo human breath isoprene. Small hydrocarbons derived from peroxidation of positions 1-6 of squalene were identified in the head space. The most unusual product, proposed to arise from peroxidation of carbon 1 and intramolecular cyclization, was a mixture of dimethylcyclopentadiene isomers. Sonication of an aqueous mixture or low O2 partial pressure favored isoprene formation.

Chemical Phenomena↗
PubMed1988

Antitumor activity of sodium linoleate.

To identify the components in a microsomal fraction from the small intestinal mucosa of mice that were responsible for preventing the proliferation of Ehrlich ascites tumor (EAT) cells, we subjected the fraction to thin-layer and gas chromatography. Assays for cytotoxicity against EAT cells in vitro indicated that linoleic acid, which was present in the free fatty acid fraction at a surprisingly high concentration, was probably the major component responsible for the antitumor activity. In further assays, using the water-soluble salt sodium linoleate, we found that sodium linoleate was more effective in vitro in killing human chronic lymphocytic leukemia lymphocytes than normal lymphocytes and mouse leukemic thymocytes than normal thymocytes. We also found that a single intraperitoneal injection of 1 mg of sodium linoleate into Swiss-Webster mice one day after the mice were inoculated with EAT cells increased the median survival from 18 (in the controls) to 48 days (in the treated mice) and prevented tumor growth completely in over 40% of the treated mice. These results are consistent with the hypothesis that linoleic acid plays a significant role in keeping the small intestine from developing primary cancers. Results also suggest a potential role for sodium linoleate in cancer therapy.

Animals↗
PubMed1987

Delayed recycling of plasma FFA in mice: revised model of turnover and oxidation.

We have reexamined the concept of the irreversible disposal rate (IDR) or fractional catabolic rate (FCR) in relation to the oxidation of a major metabolic fuel, plasma free fatty acids (FFA), in mice. We measured the disappearance of intravenously injected [1-14C]palmitate complexed to mouse serum albumin from the circulation of normal mice fed ad libitum and fasted approximately 4 h before tracer injection. We also measured the appearance of expired 14CO2 in the breath. Using multicompartmental analyses (SAAM) we found that, in contrast to earlier studies in this and other mammals where the estimated IDR has always been two to three times greater than the oxidative rate, the IDR (FCR) corresponded closely to the fractional rate of plasma FFA oxidation to CO2. This rate could be estimated accurately in a study of 10- to 15-min duration. In an extended study (5-h duration) we obtained kinetic evidence of a major transport pathway that involves delayed recycling of FFA through at least several unidentified relatively slowly turning compartments.

Animals↗
PubMed1986

A relationship between essential fatty acid and vitamin E deficiency.

To test whether vitamin E deficiency might influence the course of essential fatty acid (EFA) deficiency, Long Evans rats were fed diets containing a marginal amount (1.5% of calories) of 18:2 omega 6 or 18:3 omega 3 fatty acid with complete absence of the other and with or without vitamin E. Vitamin E contents decreased continuously in serum and liver in all rats fed the E-free diets but in the brains of only the rats fed the marginal 18:3 omega 3, E-free diet. It is considered that the vitamin E is cooxidized in the liver with 22:6 omega 3, since this fatty acid is very low in livers of the rats fed the marginal 18:2 omega 6 diet but much higher in livers of the rats fed the marginal 18:3 omega 3 diet. Brain 22:6 omega 3 values are comparable for both groups. The source of 22:6 omega 3 is evidently in the mother's milk, since following weaning there is a precipitous drop in 22:6 omega 3 in serum, liver and carcass of rats on the 18:2 omega 6--containing diet. No significant signs of EFA deficiency were seen in the E-deficient rats.

Animals↗
PubMed1986

Lipids of the retinal pigment epithelium in RCS dystrophic and normal rats.

The lipid composition of retinal pigment epithelial cells was determined for normal cells which have full phagocytic ability and for a genetic variant with impaired phagocytic function. Retinal pigment epithelial cells from 9-14-day-old congenic strains of normal (RCS-rdy+) and dystrophic (RCS-rdy/rdy) rats were separated from intact retinas and homogenized in 0.08 M Tris base, pH 7.4. The lipids were extracted using 2:1 chloroform--methanol. Fatty-acid methyl esters identified by gas chromatography were: 16:0, 17:0, 18:0, 18:1, 18:2 omega 6, 20:0, 20:2, 22:0, 20:4 omega 6, 22:4, 22:5, 22:6 omega 3. Major fatty acids for both normal and dystrophic cells were: 16:0, 18:0, 20:4 omega 6, 22:6 omega 3. One- and two-dimensional thin-layer chromatography was used to determine phospholipid composition of pigment epithelial cells at two different age groups. The relative amount of phosphatidylethanolamine was significantly higher in dystrophic RPE cells compared with normal cells (20.7% for 9-11-day-old and 17.3% for 12-14-day-old dystrophic rats). Cells from normal animals contained a higher level of phosphatidylethanolamine in the older age group whereas RPE cells from dystrophic animals contained a lower level of phosphatidylcholine in the older group. Anomalous phospholipid composition of dystrophic pigment epithelial cells may be associated with a change in cellular membranes and a defect in the cellular processes involved in phagocytic function.

Aging↗
PubMed1985

Acid-catalyzed formation of isoprene from a mevalonate-derived product using a rat liver cytosolic fraction.

Isoprene formation in a rat liver cytosolic fraction is shown to be increased 146-fold by acid treatment. This acid catalysis is dependent upon prior incubation of the cytosolic fraction with DL-mevalonate and is stimulated when the incubation also contains ATP. Formation of isoprene proceeds linearly through 5 h of acid treatment and is nearly complete at 10 h. These results suggest that the acid-catalyzed isoprene formation arises from the decomposition of dimethylallyl pyrophosphate via a carbonium ion mechanism. Chemical model studies using 3-methyl-2-buten-1-ol and 3-methyl-3-buten-1-ol (the alcohols corresponding to dimethylallyl pyrophosphate and isopentenyl pyrophosphate, respectively) confirm this hypothesis. At a pH less than or equal to 1, an 85% decomposition of 3-methyl-2-buten-1-ol to isoprene occurred after 24 h, while 3% of 3-methyl-3-buten-1-ol was converted to isoprene under identical conditions and time. It is concluded that the predominant immediate precursor of isoprene is dimethylallyl pyrophosphate and at low pH the ultimate fate of dimethylallyl pyrophosphate is complete conversion to isoprene. These conclusions have important biochemical and methodological implications.

Adenosine Triphosphate↗
PubMed1985

Evidence for an inhibitor of extrathyroidal conversion of thyroxine to 3,5,3'-triiodothyronine in sera of patients with nonthyroidal illnesses.

To determine whether an inhibitor of extrathyroidal conversion (IEC) of T4 to T3 is present in sera of patients with nonthyroidal illness (NTI), we incubated rat liver homogenate (approximately 4 mg protein) with T4 (2.5 microM) and dithiothreitol (5 mM) in the presence of evaporated diethyl ether extracts of normal or NTI sera. The T3 produced was quantified by RIA. Extracts of NTI sera caused dose-dependent inhibition in the conversion of T4 to T3. T3 produced in the presence of 20 NTI sera (1.0 mleq aliquots) was 76 +/- 5.5% (mean +/- SE; range, 18-116) that of normal sera (100 +/- 4.1% n = 10; P less than 0.01); it was more than 2 SD below the normal mean in eight patients. Inhibition of T3 production by NTI sera was correlated highly significantly with the activity of a thyroid hormone-binding inhibitor (THBI) also present in ether extracts of these sera (r = 0.82; n = 20; P less than 0.001). Since THBI may be a lipid, we studied the effect of lipids on hepatic conversion of T4 to T3. Several fatty acids were potent inhibitors of the conversion in vitro. Doses (in micromoles) causing 50% inhibition in different experiments varied between 0.2-0.52 for arachidonic acid, 0.3-0.56 for linolenic acid, 0.38-0.40 for linoleic acid, and 0.8-0.9 for oleic acid. Other lipids had less or no inhibitory activity. The inhibition of hepatic T4 5'-monodeiodination by arachidonic acid was competitive in nature (Ki, approximately 0.11 mM). Pretreatment of rat liver with phospholipase A2 for 10-60 min led to a progressive reduction in the conversion of T4 to T3. Moreover, the evaporated ether extract of phospholipase A2-treated rat liver homogenate reduced T4 to T3 conversion by untreated rat liver homogenate. There was a significant correlation between serum concentrations of free fatty acids and IEC activity in NTI sera (r = 0.74; n = 10; P less than 0.02). The various data suggest that 1) many NTI sera contain a potent IEC; 2) some fatty acids are potent IECs; 3) like THBI, IEC may be a lipid moiety; and 4) activation of tissue phospholipases may contribute importantly to reduced extrathyroidal T3 production in NTI, presumably by releasing inhibitory fatty acids that act locally first and more generally after their release into the circulation.

Adult↗
PubMed1985

Relationship between serum free fatty acids and thyroid hormone binding inhibitor in nonthyroid illnesses.

We measured the serum concentration and relative distribution of various free fatty acids (FFA) by gas/liquid chromatography in normal subjects and nonthyroid illness (NTI) patients with or without detectable serum thyroid-hormone binding inhibitor (THBI). The mean serum concentration of total FFA was 0.72 +/- 0.08 (SE) mM in eight normal subjects; it was similar (0.63 +/- 0.12) in eight THBI-negative NTI patients, but was significantly higher (3.1 +/- 1.0; P less than 0.05) in eight THBI-positive NTI patients (THBI index, 3.9 +/- 0.3 vs. 1.0 +/- 0.05 in normal subjects). Relative distribution of FFA in THBI-negative patients did not differ significantly from that in normal subjects. In THBI-positive patients, however, serum concentrations of palmitic, palmitoleic, stearic, and oleic acids were significantly above normal. Among fatty acids with appreciable THBI activity, oleic acid was most abundant in THBI-positive patients; its concentration of 1.3 +/- 0.32 mM in patients was about 6-fold higher than the corresponding normal value (0.21 +/- 0.02; P less than 0.005). The serum concentration of THBI correlated significantly with levels of both total FFA (r = 0.69; P less than 0.005) and oleic acid (r = 0.80; P less than 0.001). Addition of 0.33 mM oleic acid to THBI-negative NTI serum or 0.66 mM oleic acid to normal serum increased THBI activity to a level greater than 2 SD above the normal mean, i.e. 1.6. The various data suggest that 1) circulating FFA contribute importantly to THBI activity in sera of NTI patients; 2) oleic acid contributes more to THBI activity of NTI sera than do other FFA.

Adult↗
PubMed1984

In vitro biosynthesis of isoprene from mevalonate utilizing a rat liver cytosolic fraction.

The in vitro biosynthesis of isoprene from DL-mevalonate in the cytosolic fraction of rat liver is described. Evidence is provided suggesting a non-enzymatic formation of isoprene from isopentenyl pyrophosphate and/or dimethylallyl pyrophosphate. Furthermore, the data establish an alternate fate of the mevalonate carbon skeleton providing the first evidence that breath isoprene is linked to cholesterol biosynthesis.

Adenosine Triphosphate↗
PubMed1984

Autoxidation of Acholeplasma laidlawii membranes.

Autoxidation of Acholeplasma laidlawii membranes (with equimolar ratio of palmitic and linoleic acid) lacks an obvious induction period, and the overall rate of disappearance of substrate does not follow closely that of typical autocatalytic kinetics. Throughout the course of autoxidation, the major oxygenated products isolated were hydroperoxides (as hydroxy esters) and compounds that gave rise to trihydroxy esters. The yield of trihydroxy esters was appreciable even at the early stage of the oxidation and eventually grew to surpass that of hydroperoxides. The positions of the three hydroxyl groups in the trihydroxy esters were determined to be mostly of the 1,2,5-type rather than 1,2,3-type arrangement. To a lesser extent, some degraded products, including dimethyl nonanedioate, methyl myristate, methyl pentadecanoate, methyl hexadecadienoate and methyl heptadecadienoate also were obtained. Dimethyl nonanedioate was a previously known degradation product from 9-hydroperoxide. The shorter chain esters presumably arise from the cleavage of alpha-hydroperoxides of palmitate and linoleate moieties.

Acholeplasma laidlawii↗
PubMed1984

Restriction of maternal food intake inhibits fatty acid activation in developing rat hearts.

We studied the effect of restricting the diet of pregnant and lactating rats on the beta-oxidation of fatty acids by the developing heart in suckling pups. Control pregnant rats were fed a stock diet ad libitum. For the experimental group, food was restricted to half of the control intake on the seventh day of pregnancy and continued through lactation. The pups on the restricted diet were significantly smaller than the controls. At postnatal days 5, 14 and 21, the beta-oxidation of [1-14C] palmitate by heart homogenates was determined in the presence of ATP, carnitine and CoA. At day 21, the production of 14CO2 was 60% lower in the group on the restricted diet. Consequently, the possibility of inhibiting activation or intramitochondrial transport of fatty acids by heart mitochondria was studied in vitro using [1-14C] palmitate, [1-14C] palmitoyl CoA and [1-14C] palmitoyl carnitine. With [1-14C] palmitate, the rate of 14CO2 produced was 2464 +/- 317 cpm/mg protein/min for the control and 1682 +/- 91 for the restricted diet group. With [1-14C] palmitoyl CoA and [1-14C] palmitoyl carnitine, the oxidation rate of the experimental group was similar to control values, showing clearly that the inhibition of oxidation was from a problem with activation. A significant decrease in palmitoyl CoA synthetase activity in the heart homogenates and mitochondria of the diet-restricted pups took place.

Animals↗
PubMed1982

Lipolysis induction in adipocytes by a protein from tumor cells.

Extracts of thymic lymphoma that are obtained from AKR mice and are kept in the cold for at least several days can induce lipolytic activity in rat adipocyte suspensions. Freshly prepared extracts have low activity but contain a low molecular weight material of less than 10,000 daltons that aggregates on standing in the cold and becomes active. Treatment of aged extracts with trypsin causes a loss in activity indicating that the active material is a protein. It has been obtained in partially purified form, is relatively heat stable, and is not a lipase. Activity was also demonstrated in AKRXDBA/2 lymphoma (induced by AKR SL3-3 virus) and in transplanted lymphomas from a Friend-virus-induced erythroleukemia cell line in DBA/2 mice, but was not detected in normal thymus, spleen, liver, or other tissues. The partially purified material produced a massive fat mobilization when injected into normal mice.

Adipose Tissue↗
PubMed1982

Autoxidation of phosphatidylcholine liposomes.

Autoxidation of pure soybean phosphatidylcholine liposomes at 40 C was found to proceed without an observed induction period, but otherwise, the rates of disappearance of the linoleic acid (70% of total) and linolenic acid (6% of total) followed typical autocatalytic kinetics. Incorporation of 0.05 mol % of tocopherol into the liposomes produced an induction period of about 7 hr under the condition used for the incubation. The products formed from the autoxidation of pure soybean phosphatidylcholine liposomes were mostly 9- and 13-hydroperoxyoctadecadienoates (isolated as hydroxy esters). The yield of hydroperoxides with cis,trans configuration was about the same as those with trans,trans configuration throughout incubation period. After extensive autoxidation, a large quantity of trihydroxyoctadecenoate was also produced. When a large quantity of dipalmitoyl phosphatidylcholine was incorporated into soybean phosphatidylcholine liposomes, the rate of autoxidation decreased and was found to conform to apparent first-order kinetics. In this system, the yield of trans,trans hydroperoxides was much greater than that of cis,trans isomers at all stages of autoxidation. Late in the autoxidation of the mixed liposomes, both trihydroxyoctadecenoate and hydroxyepoxyoctadecenoate were produced in substantial quantities.

Chromatography, Gas↗