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Biomedical subjects

J A Manning

Publications and source records attributed to J A Manning.

53 records · Page 3Linked to original sources

Fatty acid binding protein. Role in esterification of absorbed long chain fatty acid in rat intestine.

Fatty acid binding protein (FABP) is a protein of 12,000 mol wt found in cytosol of intestinal mucosa and other tissues, which exhibits high affinity for long chain fatty acids. It has been suggested that FABP (which may comprise a group of closely related proteins of 12,000 mol wt) participates in cellular fatty acid transport and metabolism. Although earlier findings were consistent with this concept, the present studies were designed to examine its physiological function more directly. Everted jejunal sacs were incubated in mixed fatty acid-monoglyceride-bile acid micelles, in the presence or absence of equimolar concentrations of either of two compounds which inhibit oleate binding to FABP:flavaspidic acid-N-methyl-glucaminate and alpha-bromopalmitate. Oleate uptake, mucosal morphology, and oxidation of [14C]acetate remained unaffected by these agents, but oleate incorporation into triglyceride was inhibited by 62-64% after 4 min. The inhibition by flavaspidic acid was reversible with higher oleate concentrations. The effect of these compounds on enzymes of triglyceride biosynthesis was examined in intestinal microsomes. Neither flavaspidic acid nor alpha-bromopalmitate inhibited acyl CoA:monoglyceride acyl-transferase. Fatty acid:coenzyme A ligase activity was significantly enhanced in the presence of partially purified FABP, probably reflecting a physical effect on the fatty acid substrate or on the formation of the enzyme-substrate complex. Activity of the enzyme in the presence of 0.1 mM oleate was only modestly inhibited by equimolar flavaspidic acid and alpha-bromopalmitate, and this effect was blunted or prevented by FABP. We conclude that in everted gut sacs, inhibition of triglyceride synthesis by flavaspidic acid and alpha-bromopalmitate could not be explained as an effect on fatty acid uptake or on esterifying enzymes in the endoplasmic reticulum but rather can be interpreted as reflecting inhibition of fatty acid binding to FABP. These findings lend further support to the concept that FABP participates in cellular fatty acid transport and metabolism. It is also possible that FABP, by effecting an intracellular compartmentalization of fatty acids and acyl CoA, may play a broader role in cellular lipid metabolism.

Acids↗

Echocardiography of the tricuspid valve in congenital left ventricular-riht atrial communication.

Two patients, ages 14 and 18, with congenital left ventricular-right atrial communication through a defect in the tricuspid valve were studied by echocardiography. Proof was obtained by angiocardiography and surgery in one and ultrasonic contrast injection and angiocardiography in the other. Both presented clinically as uncomplicated ventricular septal defects. Echocardiography consistently demonstrated a high frequency, low amplitude flutter of the tricuspid valve in systole and none in diastole. Following surgical correction of the defect in one patient, there was complete disappearance of the systolic flutter. Systolic flutter has not been observed with tricuspid incompetence nor with other forms of ventricular septal defects. Fistulous communication from the aorta to the right atrium just above the tricuspid valve did not demonstrate systolic flutter in one patient studies. Tricuspid valve systolic flutter appears to be caused by the passage of the left ventricular jet blood into the right atrium through a defect in the tricuspid valve. Echocardiographic study of the tricuspid valve is of value in the recognition of the congenital left ventricular-right atrial communication.

Adolescent↗

Echocardiographic features of subpulmonic obstruction in dextro-transposition of the great vessels.

Eleven patients with dextro-transposition of the great vessels (TGV) and subpulmonic (left ventriclar outflow) obstruction documented by cardiac catheterization and angiography were studied by echocardiography. Echocardiographic features were which characterized the outflow obstruction included a) prolonged diastolic apposition of the mitral valve with the ventricular septum (10 patients), b) smaller width of the pulmonary artery as compared to the aortic root (10 cases), and c) narrowing of the subpulmonic area demonstrated by beam anglation studies through the planes of the mitral valve and the pulmonary artery (five cases). In addition, four patients showed abnormal systolic anterior movements (SAMs) of the anterior mitral leaflet resembling those observed in idiopathic hypertrophic subaortic stenosis. The SAM'S WERE LARGE IN THREE PATIENTS AND MAY HAVE ACCENTUATED THE OUTFLOW OBSTRUCTION. Additional evidence for this was provided by the movement of the pulmonary valve towards closure with the onset of the mitral SAM'S. These features were uncommon or absent in a comparison group of 17 patients with TGV and no outflow obstruction. Echocardiography appears to be useful in the diagnosis of subpulmonic muscular obstruction in TGV. Demonstration of definite mitral SAM'S IN SOME PATIENTS SUGGEST THE PRESSENCE OF ASSOCIATED FUNCTIONAL OBSTRUCTION OF THE TYPE SEEN IN IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS.

Adolescent↗

Echocardiography of the intra-atrial baffle in dextro-transposition of the great vessels.

Twelve patients with dextro-transposition of the great vessels (age eight months to four years) were studied by echocardiography following Mustard's procedure. Nine of them had also been studied preoperatively. Postoperatively all patients demonstrated structural echoes in the atrial cavity behind the pulmonary root. In ten, the motion pattern generally resembled that of a stenotic atrioventricular valve iwth a sharp anterior movement followed by flattening in diastole and rapid posterior excursion in systole. The maximum amplitude of motion ranged from 4 to 9 mm (average 6.6 mm). In the remaining two cases, the anterior diastolic movement was attenuated. Similar moving, linear echoes with larger amplitudes of motion (10-14 mm) were observed behind the tricuspid valve in four patients while poorly moving, multiple or thick conglomerate echoes (2-11 mm wide) were detected in seven cases. Echocardiographic contrast studies performed by injecting indocyanine green via catheters placed on either side of the intra-atrial baffle identified it as the source of these echoes. Following operation, coarse diastolic undulations of the mitral valve (ten cases) and the tricuspid valve (nine cases) were noted. Also, fine flutter of both atrioventricular valves, not present before, appeared after operation in three patients. These findings may be related to the altered pathway of blood flow and turbulence resulting from the insertion of the baffle in the atria. Echocardiography appears useful in delineating the character and movement pattern of the intra-atrial baffle and this may have potential in evaluating its long-term functional status.

Child, Preschool↗

Fatty acid-binding protein in small intestine. Identification, isolation, and evidence for its role in cellular fatty acid transport.

A soluble fatty acid-binding protein (FABP), mol wt approximately 12,000 is present in intestinal mucosa and other tissues that utilize fatty acids, including liver, myocardium, adipose, and kidney. This protein binds long chain fatty acids both in vivo and in vitro.FABP was isolated from rat intestine by gel filtration and isoelectric focusing. It showed a reaction of complete immunochemical identity with proteins in the 12,000 mol wt fatty acid-binding fractions of liver, myocardium, and adipose tissue supernates. (The presence of immunochemically nonidentical 12,000 mol wt FABP in these tissues is not excluded.) By quantitative radial immunodiffusion, supernatant FABP concentration in mucosa from proximal and middle thirds of jejuno-ileum significantly exceeded that in distal third, duodenum, and liver, expressed as micrograms per milligram soluble protein, micrograms per gram DNA, and micrograms per gram tissue. FABP concentration in villi was approximately three times greater than in crypts. Small quantities of FABP were present in washed nuclei-cell membrane, mitochondrial and microsomal fractions. However, the amount of FABP solubilized per milligram membrane protein was similar for all particulate fractions, and total membrane-associated FABP was only about 16% of supernatant FABP. Intestinal FABP concentration was significantly greater in animals maintained on high fat diets than on low fat; saturated and unsaturated fat diets did not differ greatly in this regard.The preponderance of FABP in villi from proximal and middle intestine, its ability to bind fatty acids in vivo as well as in vitro, and its response to changes in dietary fat intake support the concept that this protein participates in cellular fatty acid transport during fat absorption. Identical or closely related 12,000 mol wt proteins may serve similar functions in other tissues.

Adipose Tissue↗

A binding protein for fatty acids in cytosol of intestinal mucosa, liver, myocardium, and other tissues.

A protein of molecular weight approximately 12,000 which binds long-chain fatty acids and certain other lipids has been identified in cytosol of intestinal mucosa, liver, myocardium, adipose tissue, and kidney. Binding is noncovalent and is greater for unsaturated than for saturated and medium-chain fatty acids. This protein appears to be identical with the smaller of two previously described cytoplasmic anion-binding proteins. Binding of long-chain fatty acids by this protein is greater than that of other anions tested, including sulfobromophthalein, and does not depend on negative charge alone. The presence of this binding protein may explain previously observed differences in intestinal absorption among fatty acids, and the protein may participate in the utilization of long-chain fatty acids by many mammalian tissues.

Adipose Tissue↗