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Biomedical subjects

A Jobe

Publications and source records attributed to A Jobe.

At least 91 records · Page 5Linked to original sources
PubMed1981

Changes in the amount of lung and airway phosphatidylcholine in 0.5-12.5-day-old rabbits.

Newborn rabbits delivered spontaneously at term and cared for by the mothers were studied from 0.5 to 12.5 days of age. Curves are constructed to describe the changes in weight, lung and alveolar wash phosphatidylcholine and saturated phosphatidylcholine, and lung protein. The curves are complex and non-linear. However. expressing the increases in lung and alveolar wash phosphatidylcholine and saturated phosphatidylcholine pool sizes relative to animals weight results in a decreasing linear relationship from 0.5 to 12.5 days of age. By 12.5 days the ratios of lung phosphatidylcholine and saturated phosphatidylcholine to weight approximate the ratios measured for adult rabbits. The ratios of saturated to total phosphatidylcholine in the alveolar washes and lungs remained invarient throughout the study period.

Age Factors↗
PubMed1981

Surface activity following natural surfactant treatment in premature lambs.

Premature lambs with respiratory failure [CO2 partial pressure (PCO2) greater than 70 Torr] were treated with 50 mg/kg 3H-labeled natural surfactant by tracheal instillation. Minimum surface tensions of sequential samples suctioned from the airways fell from 25 +/- 3 dyn/cm before treatment to 8 +/- 5 dyn/cm after treatment and again rose to 32 +/- 2 dyn/cm at death. Minimum surface tensions of alveolar wash samples taken at death were 27 +/- 4 dyn/cm, whereas surfactant fractions reisolated from the alveolar washes lowered surface tension to under 10 dyn/cm. The alveolar washes, surfactant reisolated from the alveolar washes, and natural surfactant had similar phospholipid compositions; however, the alveolar washes contained about 40 times more protein per micromole phosphatidylcholine. The natural surfactant used for treatment apparently was inactivated by an inhibitor of surfactant function. After intravenous injections of [14C]palmitic acid, labeled saturated phosphatidylcholine appeared on the airways, indicating endogenous synthesis and secretion. However, the specific activity of the 3H-labeled saturated phosphatidylcholine in the natural surfactant used for treatment decreased by only 30 +/- 4% in the alveolar wash; thus the treatment dose was not diluted to a large extent by endogenous pools.

Animals↗
PubMed1981

Duration and characteristics of treatment of premature lambs with natural surfactant.

Premature lambs were treated with 50 mg/kg of natural surfactant lipid by tracheal instillation either at birth or shortly thereafter when respiratory failure was documented. All lambs were delivered by cesarean section and supported on infant ventilators with 100% oxygen under conditions to mimic the care of human infants with the respiratory distress syndrome. The natural surfactant used for therapy was recovered by lavage from sheep lung. Six 120-d gestational age lambs treated at birth had an initial mean oxygen pressure (pO2) value of 270 +/- 35 mm Hg; this fell within 3 h to less than 100 mm Hg. By 8.3 +/- 0.3 h after birth the lambs were in severe respiratory failure with a mean pH less than 7.1 and a mean pCO2 greater than 70 mm Hg. Six untreated lambs had pH values below 7.0 within 40 min of life despite more intensive respiratory support than was given the treated animals. Treatment with natural surfactant of 17 lambs of 120 and 130 d gestational age after early respiratory failure resulted in a prompt increase in pO2 values from about 35 mm Hg to values over 200 mm Hg and a fall in pCO2 values to normal levels in the majority of animals. This response lasted only approximately 3 h, and a second treatment was less predictably effective.

Animals↗
PubMed1981

Sequential treatments of premature lambs with an artificial surfactant and natural surfactant.

To test an artificial surfactant in vivo, six 120-d gestational age lambs were treated at birth with a mixture of a 9:1 M ratio of [14C]dipalmitoyl phosphatidylcholine (DPC) and phosphatidylglycerol at a dose of 100 mg DPC/kg. Nine other lambs were not treated. The mean PO2 values of the lambs treated with artificial surfactant were 65.7 +/- 11 mm Hg vs. 24.8 +/- 1.6 mm Hg for the untreated lambs (P less than 0.001). All lambs then were treated with 50 mg/natural surfactant lipid per kg, which promptly improved PO2 in all lambs. The PO2 values of those lambs previously treated with artificial surfactant remained greater than 100 mm Hg for 2.5 +/- 0.5 h vs. 0.9 +/- 0.3 h for lambs untreated with artificial surfactant (P less than 0.01). The pH and PCO2 values were not strikingly different between the two groups of lambs. Airway samples taken from lambs treated with artificial surfactant before treatment with natural surfactant had minimal surface tensions of 32 +/- 2.9 dyn/cm, whereas the artificial surfactant reisolated from these samples by centrifugation had minimum surface tension of 0 dyn/cm. The minimum surface tension of artificial surfactant was inhibited by fetal lung fluid from the premature lambs, whereas the minimum surface tension of natural surfactant was much less sensitive to inhibition. Artificial surfactant did not improve the pressure-volume characteristics of unventilated premature lung, whereas natural surfactant did. The change in specific activity of [14C]DPC following treatment with natural surfactant indicated that approximately 50% of the DPC initially administered was no longer associated with the airways.

Animals↗
PubMed1981

The labeling of pulmonary surfactant phosphatidylcholine in newborn and adult sheep.

The labeling of the saturated phosphatidylcholine from surfactant with radiolabeled palmitic acid was characterized in seven newborn and seven adult sheep using a repetitive sampling technique. Each animal had a small cannula placed surgically in the trachea. Following the intravenous injection of (3H) palmitic acid, surfactant samples in saline were recovered from the distal airways of each animal with fine plastic catheters over a period of 10 days. The change in specific activity of the saturated phosphatidylcholine (cpm/mumol) was used to define the kinetics of secretion and then disappearance of the labeled saturated phosphatidylcholine. Labeled saturated phosphatidylcholine accumulated in a linear fashion without an apparent initial delay for 27 hr in adult and 44 hr in newborn sheep. The labeled saturated phosphatidylcholine then decayed with mean apparent biological half-life values of 45 hr and 54 hr in adult and newborn sheep, respectively. However, these half-life estimates are compromised by the long secretory phase of the labeling curves. The characteristics of the labeling of surfactant saturated phosphatidylcholine in sheep may be more representative of surfactant metabolism in large mammals than previous studies in small rodents.

Animals↗
PubMed1980

The in vivo labeling with acetate and palmitate of lung phospholipids from developing and adult rabbits.

The labeling with radiolabeled acetate and palmitate of lung, microsomes isolated from lung, and surfactant phospholipids from adult, 3-day-old, and newborn rabbits was studied. The half-life of phosphatidylcholine from lung and microsomal fractions was shorter when labeled with acetate than when labeled with palmitate. Half-time values similarly measured for phosphatidylglycerol, phosphatidylinositol or phosphatidylethanolamine were not different for the two labels. Acetate and palmitate-labeled phospholipids appeared in the surfactant fraction with similar accumulation curves. The relative specific activities of acetate-labeled phosphatidylcholine from adult, 3-day-old, and newborn rabbits, respectively, were 1.30, 1.86 and 1.77 times those measured for those measured for the palmitate label. Surfactant phosphatidylinositol and phosphatidylethanolamine from 3-day-old animals similarly were labeled preferentially with acetate. However, phosphatidylglycerol purified from the surfactant fraction contained equivalent relative amounts of the acetate and palmitate labels in 3-day-old and adult rabbits. These results suggest that the type II pneumocyte may use acetate preferentially for the synthesis of palmitic acid which then is incorporated into surfactant phospholipids.

Acetates↗
PubMed1980

Surfactant metabolism of newborn lamb lungs studied in vivo.

Surfactant, microsomal, and lamellar body fractions were isolated from the lungs of 5-day-old lambs 0.21-55 h after the intravenous injection of radiolabeled palmitic acid. The specific activities as cpm/mumol phospholipid phosphate of phosphatidylcholine, saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine were measured. The palmitate-labeled phospholipids disappeared from the lung parenchyma with a half-life of approximately 50 h. The radiolabel disappeared from phosphatidylcholine, saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine of microsomal fractions with initial half-life values of 4.5, 4.6, 1.9, and 23.9 h, respectively. The labeled phospholipids rapidly appeared in the lamellar body fraction and accumulated in the surfactant of the lambs in a linear fashion for 35 h. The curves for the labeling of surfactant with radiolabeled saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine were similar to the curve for phosphatidylcholine.

Animals↗
PubMed1980

Surfactant phospholipid metabolism in 3-day and 3-day postmature rabbits in vivo.

Three-day-old normal and 3-day postmature rabbits (prepared by human chorionic gonadotropin treatment of the does) were given injections of the radiolabeled phospholipid precursors palmitic acid, choline, and glycerol. The specific activities as cpm/mumol phospholipid phosphate were measured for phosphatidylcholine, disaturated phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, and phosphatidylethanolamine from lung and alveolar wash fraction lipid extracts of 3-day-old rabbits. Specific activities similarly were measured for phosphatidylcholine and disaturated phosphatidylcholine from postmature rabbits. Curves describing the appearance of labeled phospholipids into the alveolar wash fraction demonstrated that in both 3-day and postmature rabbits, phospholipid secretion was delayed for 3 to 4 hr. Thereafter, there was a rapid accumulation of labeled phospholipids until 12 to 16 hr after labeled precursor injection. The curves were similar for all measured phospholipids and all labeled precursors studied. The phospholipid compositions of lung and alveolar wash fraction lipid extracts were determined by analysis of the various phospholipids separated by two-dimensional thin-layer chromatography. Forty percent of lung samples and 35% of alveolar wash samples from postmature rabbits contained no detectable phosphatidylglycerol, whereas all 22 lung and surfactant samples from 3-day-old rabbits contained this phospholipid.

Age Factors↗
PubMed1979

Kinetics of the in vivo labeling of the acyl groups of rabbit lung phosphatidylcholine and disaturated phosphatidylcholine.

The kinetics of labeling of lung phosphatidylcholine and disaturated phosphatidylcholine were studied for periods from 0.75--120 min following intravenous injection of radiolabeled palmitic acid and choline into 3-day-old rabbits. The labeled palmitic acid was cleared rapidly from plasma, and rapidly appeared with identical incorporation kinetics in both phosphatidylcholine and disaturated phosphatidylcholine. The 2-acyl positions of both phosphatidylcholine and disaturated phosphatidylcholine were labeled preferentially soon after [14C]palmitic acid injection. The specific activities of palmitic acid in the 2-acyl positions of phosphatidylcholine and disaturated phosphatidylcholine 0.75 min after injection of labeled palmitic acid were 3.4 and 1.9 times, respectively, the specific activities of palmitic acid in the 1-acyl positions. By 120 min the label had randomized between the 1-acyl and 2-acyl positions, and the kinetics of that randomization were defined for both phosphatidylcholine and disaturated phosphatidylcholine. Choline did not pulse label lung phosphatidylcholine or disaturated phosphatidylcholine. The choline label appeared with equal specific activities in both phosphatidylcholine and disaturated phosphatidylcholine. Thus no analysis of the de novo synthesized product via the CDP-choline pathway was possible.

Acylation↗
PubMed1979

An in vivo comparison of acetate and palmitate as precursors of surfactant phosphatidylcholine.

3-Day-old rabbits were injected simultaneously with [(3)H]acetate and [(14)C]-palmitic acid. The specific activities of lung, lamellar body and surfactant phosphatidylcholine and disaturated phosphatidylcholine were measured at time intervals from 10 min to 23 h following isotope administration. Palmitic acid contained 87% of the acetate radioactivity recovered from lung and surfactant phosphatidylcholine. The relative specific activities of surfactant phosphatidylcholine and disturated phosphatidylcholine labeled with acetate were 2.02 and 1.86 times those measured using the palmitic acid label. Apparently the palmitic acid synthesized from acetate is preferentially incorporated into lung phosphatidylcholines and disaturated phosphatidylcholines which are destined to become surfactant.

Acetates↗
PubMed1979

The labeling of lung phosphatidylcholine in premature rabbits.

Lung phosphatidylcholine metabolism was studied in vivo in premature rabbits delivered by cesarean section as early in gestation as compatible with prolonged viability (28.9 days). The newborn rabbits initially required supplemental oxygen and had respiratory distress. The amount of phosphatidylcholine isolated from the lung parenchyma changed little over the first 3 days of life, while phosphatidylcholine in the alveolar wash increased in 3 days from 0.05--3.1 mumol/50 g animal. The phosphatidylcholine of the lungs of the premature rabbits was pulse labeled with isotopically labeled palmitic acid, choline, and phosphate given to the pregnant does 10 min before delivery of the newborns. After the initial incorporation period, the total amount of radioactive precursor palmitic acid, choline, or 32P) incorporated into lung phosphatidylcholine did not change for a period of 4 days. Labeled phosphatidylcholine was detected initially in alveolar wash 3 hr after administration of the three precursors and continued to accumulate for many hours. The biological half-life values for lung and alveolar phosphatidylcholine indicated that phosphatidylcholine was turning over very slowly. However, if the effect of dilution on the measured specific activity caused by phosphatidylcholine accumulation was considered, virtually no labeled alveolar or lung phosphatidylcholine disappeared during the 3--4 days of these observations. These results with premature newborn rabbits were similar to those for term newborn rabbits, but different from similar measurements made in the adult rabbit.

Age Factors↗
PubMed1979

The labelling of pulmonary surfactant phosphatidylcholine in 19-31-days-old lambs.

The labelling of surfactant phosphatidylcholine and disaturated phosphatidylcholine was studied in 19-31-days-old lambs. Following the placement of small bore tracheal catheters, the animals were given radioactively labelled palmitic acid and/or choline by intravenous injection and multiple samples were recovered from the distal airways of each animal via a small catheter. The specific activities of the phosphatidylcholine and/or disaturated phosphatidylcholine were measured in these samples of surfactant. The labelled phospholipids accumulated in the samples of surfactant in a linear fashion; the mean time required to reach maximal specific activities in phosphatidylcholine and saturated phosphatidylcholine with either palmitic acid or choline as precursor was 28 h. Subsequently the specific activities of the labelled phospholipids from the surfactant samples decreased semi-logarithmically. The mean t1/2 for phosphatidylcholine and disaturated phosphatidylcholine labelled with radioactive palmitic acid was 35 h. The saturated phosphatidylcholine labelled with radioactive choline had a t1/2 of 251 h. The results demonstrate that surfactant labelling studies can be done by multiple sampling of single large animals.

Animals↗
PubMed1978

Labeling of phosphatidylcholine in the alveolar wash of rabbits in utero.

Radioactive palmitic acid, choline, and phosphate were given to rabbits 28 and 30 days pregnant and the labeling;of phosphatidylcholine in the fetal lung and alveolar wash was studied. Labeled phosphatidylcholine was detected initially in the alveolar wash three hours after isotope administration. The three-hour delay was independent of precursor studied or gestational age, and the radioactive phosphatidylcholine continued to accumulate in the wash fluid for at least 18 hours. Each labeled precursor of phosphatidylcholine sequentially labeled the phosphatidylcholine from microsomal, lamellar body and alveolar wash lung fractions of the 30 day fetal animals.

Animals↗