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Biomedical subjects

W J Carter

Publications and source records attributed to W J Carter.

At least 37 records · Page 2Linked to original sources
PubMed1988

Red blood cell and plasma fatty acid composition in diabetes mellitus.

Arachidonic acid deficiency and increased linoleic acid levels have been a consistent finding in a variety of tissues in experimental diabetes. To determine if patients with type II non-insulin-dependent diabetes show changes in red blood cell and plasma fatty acid composition, a group of non-insulin-dependent diabetic patients were studied prior to and following treatment with glyburide which substantially improved their diabetic control. Red blood cell and plasma fatty acid composition was compared with that of a group of nondiabetic subjects and to red cell fatty acid composition in normal and streptozotocin diabetic rats. The diabetic patients had no changes in linoleic or arachidonic acid levels prior to treatment and no changes following glyburide therapy. These studies and the available literature suggest to us that either more severe diabetes is required to produce the fatty acid abnormalities described in the diabetic rat or that there is a fundamental species difference in the mechanism of diabetes or in fatty acid metabolism between the human and the rat which allows the human diabetic to more easily maintain normal tissue fatty acid composition.

Diabetes Mellitus, Type 2↗
PubMed1988

Altered fatty acid composition in the plasma, platelets, and aorta of the streptozotocin-induced diabetic rat.

Decreased arachidonate levels have been described in various tissues of the streptozotocin-induced diabetic rat. However, reported arachidonate changes in platelets from diabetic patients have been variable. In this communication, we describe experiments that indicate that in the short-term streptozotocin diabetic rat (2 to 3 weeks), the fatty acid composition of plasma and red blood cell lipids was altered but remained unchanged in platelet and aorta phospholipids. The altered fatty acid composition of the diabetic red blood cells and plasma cholesterol esters and phospholipids was similar to that previously found in the diabetic liver. However, in long-term diabetes (6 weeks), the phospholipid fatty acid composition of the platelet and aorta became significantly altered. Thus, in the 6-week diabetic platelet, there were increases of linoleate, dihomo-gamma-linolenate, docosapentaenoate (C22:5n-3), and docosahexaenoate, and decreases of oleate, arachidonate, and docosatetraenoate. In the aorta, there were increases of linoleate, eicosapentaenoate, and docosahexaenoate, and decreases of arachidonate, docosatetraenoate, and docosapentaenoate (C22:5n-6). Results from these experiments indicate that the fatty acid composition of plasma and red blood cell lipids was altered in short-term diabetes (2 to 3 weeks), but that of platelet and aorta phospholipids was not changed until more prolonged diabetes was present. Insulin treatment of the diabetic rat increased the levels of palmitoleate and oleate and decreased the levels of linoleate in platelet and aorta lipids from insulin-treated diabetic rats, suggesting an overcorrection of diminished delta 9 and delta 6 fatty acid desaturation as compared with the nondiabetic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effect of graded doses of tri-iodothyronine on ventricular myosin ATPase activity and isomyosin profile in young and old rats.

Ventricular myosin ATPase activity, V1 isomyosin content and serum T3 (tri-iodothyronine) values decrease with age in male Fischer 344 rats. To determine if the age decrement in ATPase activity and V1 isomyosin content are caused by decreased T3 levels or an age-related decrease in V1 isomyosin induction by T3, 3-, 12- and 24-month-old male Fischer 344 rats were given constant T3 infusions by osmotic minipump. Rats at all ages were given 0.75, 5 and 15 micrograms(/100 g per 24 h) doses of T3, whereas 12- and 24-month-old rats were given an additional 0.4 microgram dose. In control rats, T3 levels decreased from 97 +/- 2.7 at 3 months to 75 +/- 4.7 ng/100 ml at 24 months. Likewise, Ca2+-activated myosin ATPase activity decreased from 1.04 +/- 0.05 to 0.68 +/- 0.05 mumol of Pi/min per mg of protein, and the relative proportion of V1 of isomyosin decreased from 90 +/- 4.0 to 26 +/- 2.0%. The lowest (0.4 microgram) T3 dose, which was sufficient to restore T3 levels in 24-month-old animals to 3-month control values, abolished the age decrement in myosin ATPase activity and markedly increased the proportion of V1 isomyosin present in the ventricle. These findings indicate that the senescent ventricle responds readily to small doses of T3 and strongly suggest that the age decrement in serum T3 levels is sufficient to contribute to the age-related decrease in myosin ATPase activity and V1 isomyosin content. Since these parameters correlate with ventricular contractility, the age decrement in T3 levels may also contribute to the decreased ventricular contractility and cardiac output observed in senescent rats.

Adenosine Triphosphatases↗
PubMed1987

Comparison of the effect of a protein-free and restricted high protein-low carbohydrate diet on ventricular myosin ATPase activity and isomyosin profile in young rats: evidence that protein-depleted animals are euthyroid.

Young rats fed a protein-deficient diet have elevated total triiodothyronine (T3) levels in spite of decreased skeletal muscle protein turnover. Interpretation of the thyroid status of these animals is complicated by increased T3 binding by serum proteins. Free T3 levels ranging from normal to low and decreased resting oxygen consumption have been reported. To investigate the thyroid status of animals fed a protein-free diet, ventricular myosin ATPase activity and isomyosin profile have been used as an index of thyroid hormone activity. The effect of the protein-free diet has been compared to a restricted high protein-low carbohydrate diet, which causes clear evidence of decreased thyroid hormone effect. After 28 d, calcium-activated myosin ATPase activity was 1.50 +/- 0.05 mumol Pi/(mg protein.min) in animals fed the basal diet, 1.16 +/- 0.03 mumol Pi/(mg protein.min) in animals fed the restricted high protein-low carbohydrate diet and 1.48 +/- 0.04 mumol Pi/(mg protein.min) in animals fed the protein-free diet. In addition, a shift in isomyosin content with the appearance of V2 and V3 isomyosins occurred with the restricted high protein-low carbohydrate diet but not the protein-free diet. The failure of the protein-depleted rats to decrease myosin ATPase activity and alter isomyosin content suggests that they are euthyroid.

Adenosine Triphosphatases↗
PubMed1986

Geriatric Rehabilitation Unit: a 3-year outcome evaluation.

One-hundred-ninety elderly (mean age 75.8 years), disabled patients at risk of being institutionalized due to stroke, acute medical problems, dementia, and other illnesses completed a rehabilitation program at the Geriatric Rehabilitation Unit (GRU). A retrospective study to measure possible impacts of rehabilitation on functional status and placement at discharge from the GRU and on living situation 1 year postdischarge showed an improvement of functional status after rehabilitation in nearly all patients. By discharge, the number of patients with partial or total activities of daily living (ADL) independence increased from 87 to 173, ambulatory patients increased from 42 to 127, continent patients from 89 to 141 and mentally clear patients from 40 to 91. Higher ratings in these parameters at discharge were associated with better placement and significantly lower mortality 1 year postdischarge. Patients placed in noninstitutional settings had a lower (21%) mortality rate when compared with patients placed in nursing homes (mortality 45%). The GRU program is clearly associated with improved outcome of care.

Activities of Daily Living↗
PubMed1985

Influence of hypo- and hyperthyroidism on rat liver glycerophospholipid metabolism.

The effects of hyper- and hypothyroidism on enzyme activities involved in phospholipid metabolism in the rat liver were studied. Hyperthyroidism significantly decreases activities of both microsomal acyl-CoA:glycero-3-phosphate acyltransferase (GPAT) (34%, p less than 0.01) and microsomal acyl-CoA:1-acylglycero-3-phosphocholine acyltransferase (GPCAT) (28-33%, p less than 0.01). This may contribute to the decreased proportions of certain unsaturated fatty acids found in microsomal phosphoglycerides in hyperthyroidism. Mitochondrial GPAT, phospholipase A2 and cytosol lysophospholipase are unaffected by hyperthyroidism. In contrast, hypothyroidism stimulates mitochondrial GPAT (38%, p less than 0.01) and microsomal GPCAT (14-19%) activities but decreases both mitochondrial phospholipase A2 (36%, p less than 0.01) and cytosol lysophospholipase (56%, p less than 0.01) activities. The increased GPCAT activity may contribute to the increased proportions of certain unsaturated fatty acids found in microsomal phosphoglycerides in hypothyroidism. Triiodothyronine (T3) treatment of the hypothyroid rat (25 micrograms/100 g body weight/day for four days) corrected phospholipase A2 and lysophospholipase activities to the level of the control rat, but failed to correct the increased mitochondrial GPAT activity and not only corrected but lowered GPCAT activity to the level of the hyperthyroid rat.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1985

Effect of thyroid hormone on protein turnover in cultured cardiac myocytes.

Since systemic actions of thyroid hormone increase cardiac work, direct effects of T3 on myocardial protein turnover may be obscured in the intact animal. For this reason, the effects of T3 on synthesis and degradation of cellular protein were measured in replicate cultures of cardiac myocytes obtained from chick embryos. During the first 3 days of exposure, 10(-8) M T3 increased the fractional rate of protein synthesis 10% to 16% and the fractional rate of cell growth 20% to 40% with no change in protein degradation. During the fourth and fifth days of 10(-8) M T3 exposure, fractional synthesis rates in T3 cultures increased 15% to 19% but fractional degradation rates also increased 17% to 29% so that growth rates in T3 cultures fell to control levels. Similar changes in myocardial protein turnover have occurred in response to T3 treatment in intact animals. T3 treatment caused a disproportionately large increase in the rate of myosin heavy chain turnover when compared to total cellular protein and actin. This may be related to the change in amounts of myocardial isomyosins occurring in response to thyroid hormone treatment.

Actins↗
PubMed1984

Effect of a protein-free diet on muscle protein turnover and nitrogen conservation in euthyroid and hyperthyroid rats.

Although protein turnover in skeletal muscle is increased in hyperthyroidism and decreased in hypothyroidism, a deficient protein intake tends to increase serum T3 (tri-iodothyronine) while decreasing muscle protein turnover. To determine whether this diet-induced decrease in protein turnover can occur independent of thyroid status, we have examined muscle protein turnover and nitrogen conservation in hyperthyroid rats fed on a protein-free diet. After inducing hyperthyroidism by giving 20 micrograms of T3/100g body wt. daily for 7 days, groups of euthyroid and hyperthyroid animals were divided into subgroups fed on basal and protein-free diets. Muscle protein turnover was measured by N tau-methylhistidine excretion and [14C]tyrosine infusion. Urinary nitrogen output of euthyroid and hyperthyroid animals fed on the protein-free diet was also measured. Although hyperthyroidism increased the baseline rates of muscle protein synthesis and degradation, it did not prevent a decrease in these values in response to protein depletion. Furthermore, hyperthyroid rats showed greatly decreased nitrogen excretion in response to the protein-free diet, although not to values for euthyroid rats. These findings suggest that protein depletion made the experimental animals less responsive to the protein-catabolic effects of T3.

Animals↗
PubMed1984

Effects of streptozotocin-induced diabetes on phosphoglyceride metabolism of the rat liver.

We have studied the effect of streptozotocin (SZ)-induced diabetes on fatty acyltransferase and phospholipase enzyme activities involved in the synthesis and degradation of rat liver phosphoglycerides. Neither mitochondrial nor microsomal acyl-CoA:glycerol 3-phosphate acyltransferase (GPAT) activity was altered, although insulin treatment stimulated mitochondrial GPAT activity. However, microsomal acyl-CoA:1-acylglycerol 3-phosphate acyltransferase (1-acyl-GPAT) activity increased (24-33 per cent, p less than 0.01) in the diabetic animals using 3 different acyl-CoA donors: palmitoyl-CoA, oleoyl-CoA and linoleoyl-CoA. SZ-induced diabetes also increased acyl-CoA;1-acylglycerol 3-phosphorylcholine acyltransferase (GPCAT) activity (38-45 per cent, p less than 0.01) with 3 different acyl-CoA donors: oleoyl-CoA, linoleoyl-CoA and arachidonoyl-CoA. 1-acyl-GPAT and GPCAT activity returned to normal with insulin treatment. In contrast to the increased activity of the microsomal fatty acyl-transferases 1-acyl-GPAT and GPCAT, SZ-induced diabetes decreased mitochondrial phospholipase A2 activity and lysophospholipase activity (49-70 per cent, p less than 0.01). Insulin treatment of the diabetic rats corrected the decreased lysophospholipase and stimulated phospholipase A2 activity 35 per cent higher than controls. Since microsomal 1-acyl-GPAT and GPCAT are known to have higher activity toward unsaturated fatty acyl-CoA donors, the increased GPCAT activity coupled with the decreased lysophospholipase activity and the increased 1-acyl-GPAT activity in diabetes would tend to increase the formation of newly synthesized phospholipids containing unsaturated fatty acids. This mechanism plus the decreased fatty acid desaturase (4) may be the factors which alter the fatty acid composition of phosphoglycerides in diabetic rat liver microsomes.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗
PubMed1984

Effects of streptozotocin-induced diabetes on microsomal long-chain fatty acyl-CoA synthetase and hydrolase.

Streptozotocin-induced diabetes significantly decreased rat liver microsomal long-chain fatty acyl-CoA (LCA-CoA) hydrolase. The decrease was observed using either palmitoyl-CoA (35 per cent, p less than 0.01) or oleoyl-CoA (23 per cent, p less than 0.01) as the substrate for the enzyme. Under the same conditions, diabetes did not significantly alter activity of LCA-CoA synthetase. Daily subcutaneous injections of protamine zinc insulin (10-12 units/day) into the diabetic rats returned their blood glucose to normal but only partially corrected the LCA-CoA hydrolase activity and did not effect LCA-CoA synthetase activity. The decreased LCA-CoA hydrolase and the unchanged LCA-CoA synthetase activities in the diabetic rat liver were interpreted as factors that may contribute to elevation of fatty acyl-CoA levels in the diabetic liver.

Animals↗
PubMed1983

Altered microsomal phospholipid composition in the streptozotocin diabetic rat.

Streptozotocin diabetes in the rat alters liver microsomal membrane fatty acid composition. The present study was undertaken to determine if such changes in fatty acid composition were due to changes in the amount of individual phosphoglycerides or to disproportionate changes in fatty acid composition in any of the individual phosphoglycerides. The diabetic animals showed a small increase in total microsomal phospholipid, which is due to a selective increase in the phosphatidylethanolamine fraction. The changes in fatty acid composition in the total lipid extract (decreased palmitoleic, oleic and arachidonic acids and increased linoleic and docosahexaenoic acids) from the diabetic animals were present in both the major phosphoglycerides, phosphatidylcholine and phosphatidylethanolamine, with very little change in fatty acid composition in the phosphatidylserine and inositol fraction. Further studies are necessary to delineate the cause of the abnormal membrane phospholipid composition in the diabetic animal.

Animals↗
PubMed1982

Fatty acid desaturation and microsomal lipid fatty acid composition in experimental hypothyroidism.

We have studied the influence of experimental hypothyroidism in the rat on the synthesis of unsaturated fatty acids and on liver microsomal lipid fatty acid composition. Hypothyroid rats demonstrated an 80% decrease in delta 9 (stearate) desaturation and a 43% decrease in delta 6 (linoleate) desaturation. Liver microsomal fatty acid composition was altered in the hypothyroid animals with a significantly decreased proportion of arachidonate and increased proportions of linoleate, eicosa-8,11,14-trienoate, eicosapentaenoate and docosahexaenoate. The bulk of these changes occurred in both of the two major phospholipid components, phosphatidylcholine and phosphatidylethanolamine. All of the changes were corrected by treatment of the hypothyroid rat with 25 micrograms of tri-iodothyronine/100 g body wt. twice daily. The diminished delta 9 desaturation did not lead to any changes in fatty acid composition. The increased linoleate and decreased arachidonate levels may be due to the diminished delta 6 desaturase activity, the rate-controlling step in the conversion of linoleate into arachidonate. The increases in the proportions of the other polyunsaturated fatty acid components cannot be explained by changes in the synthesis of unsaturated fatty acids, but are probably due to diminished utilization of these fatty acids.

Animals↗
PubMed1982

Effects of experimental hyperthyroidism on protein turnover in skeletal and cardiac muscle as measured by [14C]tyrosine infusion.

The effect of T3 (3,3',5-tri-iodothyronine) on protein turnover in skeletal and cardiac muscle was measured in intact rats by means of a 6 h [14C]tyrosine-infusion technique. Treatment with 25-30 micrograms of T3/100 g body wt. daily for 4-7 days increased the fractional rate of protein synthesis in skeletal muscle. Since the fractional growth rate of the muscle was decreased or unchanged, T3 treatment increased the rate of muscle protein breakdown. These findings suggest that increased protein degradation is an important factor in decreasing skeletal-muscle mass in hyperthyroidism. In contrast with skeletal muscle, T3 treatment for 7 days caused an equivalent increase in the rate of cardiac muscle growth and protein synthesis. This suggests that hyperthyroidism does not increase protein breakdown in heart muscle as it does in skeletal muscle. The failure of T3 to increase proteolysis in heart muscle may be due to a different action on the cardiac myocyte or to systemic effects of T3 which increase cardiac work.

Animals↗