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Biomedical subjects

J A Manning

Publications and source records attributed to J A Manning.

18 recordsLinked to original sources
PubMed1991

In situ binding of fatty acids to the liver fatty acid binding protein: analysis using 3-[125I]iodo-4-azido-N-hexadecylsalicylamide.

A photoactivatable radioiodinated fatty acid analogue, 3-[125I]iodo-4-azido-N-hexadecylsalicylamide (125I-AHS) has been synthesized and used to investigate the involvement of cellular lipid carriers in hepatic fatty acid utilization. Photoactivation of Hep G2 internalized 125I-AHS revealed that several cellular proteins were crosslinked with the radiolabeled fatty acid analogue. Three predominant proteins in the membrane fraction of the cell with molecular masses 17, 50 and 127 kDa were crosslinked with the lipid analogue, as determined using autoradiography after SDS-PAGE. Three other proteins in the soluble fraction of the cell, with molecular masses 14, 24 and 35 kDa, were also labeled in situ. In contrast to the other labeled proteins, the fatty acid analogue accumulated on the cytoplasmic 14 kDa protein in a time and temperature dependent fashion. The in situ-labeled 14 kDa protein was identified from primary rat hepatocytes as the liver fatty acid binding protein by partial purification and its ability to be immunoprecipitated with immunospecific L-FABP antiserum. Collectively the results indicate that fatty acids traverse the plasma membrane and are bound cytoplasmically by the liver fatty acid binding protein, as well as other proteins in the cell. This represents the first demonstration in intact hepatocytes that the liver fatty acid binding protein participates in the process of intracellular fatty acid trafficking, and supports a model in which cytoplasmic lipid carriers solubilize fatty acids as a step in their metabolic utilization.

Affinity Labels↗
PubMed1991

Isolation and characterization of fatty acid binding protein in the liver of the nurse shark, Ginglymostoma cirratum.

1. A 14.5 kDa fatty acid binding protein was isolated from the liver of the nurse shark, Ginglymostoma cirratum. 2. Purified shark liver FABP (pI = 5.4) bound oleic acid at a single site with an affinity similar to that of mammalian FABP. 3. The apparent size, pI and amino acid composition of shark liver FABP indicate a close structural relationship between this protein and mammalian heart FABP.

Animals↗
PubMed1990

The effects of indomethacin on renal function and intracranial hemorrhage in infants with patent ductus arteriosus.

The effects of indomethacin on patent ductus arteriosus (PDA) were retrospectively studied by evaluating 1,600 consecutive infants less than 36 weeks gestation from 1983 to 1986. Two hundred thirteen infants were diagnosed with a PDA, and 102 infants received indomethacin. Indomethacin was associated with successful PDA closure in 81 infants (79%), with 59 infants (58%) closing after a single dose. No cases of renal failure were observed after indomethacin. Nine infants were treated despite a creatinine (Cr) value greater than or equal to 1.5 mg/dl. Cr improved in all these infants after therapy. Blood urea nitrogen values were greater than or equal to 30 mg/dl in 22 infants at the time of treatment; 18 infants (82%) improved. An intracranial hemorrhage (ICH) was detected in 23 infants (22%) by cranial ultrasound prior to indomethacin; there was no progression after treatment. Data suggest that indomethacin is highly associated with closure of a PDA, and therapy did not result in prolonged renal dysfunction or worsening ICH.

Acute Kidney Injury↗
PubMed1979

Sex differences in long chain fatty acid utilization and fatty acid binding protein concentration in rat liver.

Female sex and estrogen administration are associated with increased hepatic production of triglyceride-rich lipoproteins; the basis for this has not been fully elucidated. Inasmuch as hepatic lipoprotein production is also influenced by FFA availability and triglyceride biosynthesis, we investigated sex differences in FFA utilization in rat hepatocyte suspensions and in the components of the triglyceride biosynthetic pathway. Isolated adult rat hepatocyte suspensions were incubated with albumin-bound [(14)C]oleate for up to 15 min. At physiological and low oleate concentrations, cells from females incorporated significantly more (14)C into glycerolipids, especially triglycerides, and into oxidation products than did male cells, per milligram cell protein. At 0.44 mM oleate, incorporation into triglycerides in female cells was approximately twice that in male cells. Comparable sex differences were observed in cells from fasted animals and when [(14)C]-glycerol incorporation was measured. At higher oleate concentrations, i.e., fatty acid:albumin mole ratios in excess of 2:1, these sex differences were no longer demonstrable, suggesting that maximal rates of fatty acid esterification and oxidation were similar in female and male cells. In female and male hepatic microsomes, specific activities of long chain acyl coenzyme A synthetase, phosphatidate phosphohydrolase, and diglyceride acyltransferase were similar, but glycerol-3-phosphate acyltransferase activity was slightly greater in females at certain substrate concentrations. Microsomal incorporation of [(14)C]oleate into total glycerolipids was not significantly greater in females. In further contrast to intact cells, microsomal incorporation of [(14)C]oleate into triglycerides, although significantly greater in female microsomes, accounted for only a small fraction of the fatty acid esterified.The binding affinity and stoichiometry of partially purified female hepatic fatty acid binding protein (FABP) were similar to those of male FABP. In contrast, the concentration of FABP, per milligram cytosolic protein, was 44% greater in female liver than in male, as indicated by measurement of [(14)C]oleate binding and of 280 nm OD in the FABP fraction of 105,000 g supernate after gel filtration chromatography. These experiments demonstrate profound sex differences in hepatocyte utilization of long chain fatty acids at concentrations within and below the physiological range, and suggest that these are attributable at least in part to corresponding differences in cytosolic FABP concentration. At higher FFA concentrations, sex differences in hepatocyte FFA utilization are virtually eliminated, suggesting that under these conditions, differences in FABP concentration are not rate determining. Sex differences in hepatic lipoprotein production may largely reflect these important differences in the initial stages of hepatocyte FFA utilization.

Albumins↗
PubMed1977

Trial of bivalent influenza A vaccine in high-risk infants.

A vaccine trial involving 50 high-risk infants, aged six to 36 months, was performed for evaluation of the safety of a split-virus bivalent influenza A vaccine. After immunization, 18% of the infants developed a fever of greater than or equal to 100 F and 7% had fever of greater than or equal to 102 F. Other reactions to the vaccine were few. However, the reaction index of these high-risk infants to the bivalent vaccine was higher than those of older children receiving the same vaccine and normal infants receiving the monovalent vaccine. Forty-one percent of the infants responded with a titer of hemagglutination-inhibiting antibody of greater than or equal to 1:20 to the A/Victoria/75 component of the bivalent vaccine, and 35% responded to the A/New Jersey/8/76 component. This result suggested that this vaccine used in two doses would be an effective vaccine for infants. The infants generally tolerated the vaccine well. Nevertheless, the rapid development of fever would be of concern in the infant whose underlying disease was marginally compensated.

Antibodies, Viral↗
PubMed1976

Echocardiographic studies of abnormalities associated with coarctation of the aorta.

Echocardiograms were performed in thirty-six patients (aged 4 to 36 years) with proven coarctation of the aorta. Nineteen patients (53%) were found to have marked diastolic eccentricities of their aortic valves (Eccentricity Index greater 1.5), indicating the presence of bicuspid aortic valves. One of these patients also had multilayered aortic root echoes in diastole. Five patients had angiographic proof of their aortic valve morphologies which corroborated the echo findings. Five patients with bicuspid aortic valves showed mitral valve diastolic flutter indicative of aortic regurgitation. Idiopathic hypertrophic subaortic stenosis (IHSS) was suspected in four patients (11%) with abnormal systolic anterior motion of the mitral valve; three of these patients also had asymmetric septal hypertrophy. There was catheterization proof of IHSS in one patient. Two patients (5.6%) demonstrated mitral valve proplapse.

Amyl Nitrite↗
PubMed1976

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↗
PubMed1975

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↗
PubMed1975

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↗
PubMed1975

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↗