Bronchoalveolar lavage lipids in idiopathic pulmonary fibrosis.
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Bronchoalveolar Lavage Fluid↗
Biomedical subjects
R B Low
Publications and source records attributed to R B Low.
Contractile cells in normal and fibrotic lung.
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Animals↗
The efficacy of ground versus helicopter transport in patient outcome.
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Aircraft↗
Acute respiratory arrest due to hypokalemia.
An uncommon but treatable etiology of acute respiratory failure is hypokalemia. A 36-year-old woman with previously undiagnosed distal renal tubular acidosis presented with foot and ankle swelling that was being treated with furosemide. She had been seen by three physicians within 24 hours and was diagnosed as having depression or hysterical conversion reaction. Her symptoms progressed to respiratory arrest. Initial treatment consisted of administering 40 mEq of KCl over one hour through a central venous line. The patient recovered rapidly and was weaned off a respirator within 24 hours of admission.
Acute Disease↗
Accuracy of blood pressure measurements made aboard helicopters.
Hemodynamically unstable patients will benefit from therapy to control their blood pressure only if this pressure can be determined with accuracy. We compared the accuracy of arterial blood pressure measurements taken aboard helicopters by palpation with a Doppler device and with an oscillometric device. Twenty critically ill patients who required an intra-arterial line had simultaneous blood pressures taken invasively and with one or more of the nonivasive techniques. A total of 222 comparisons was made. Error measurements are reported as mean +/- standard deviation; a high standard deviation implies inaccuracy in individual noninvasive measurements. Mean palpation error was 19 +/- 22 torr, mean Doppler error was 8 +/- 17 torr, mean oscillometric systolic error was 0 +/- 33 torr, and mean oscillometric mean blood pressure measurement error was 10 +/- 15 torr. A blood pressure undetectable by noninvasive means was no guarantee of a low arterial pressure: four patients with arterial systolic pressures from 45 to 138 torr had nonpalpable pulses; three patients had systolic pressures between 98 and 143 torr that were not detectable with the Doppler device; and two patients had systolic pressures of 70 and 110 torr that were undetectable by the oscillometric device. We conclude that aboard helicopters some ill patients cannot have accurate noninvasive measurement of their arterial blood pressure made with present technology. Relying on inaccurate blood pressure measurements may lead to therapeutic mishaps.
Aircraft↗
Alpha-smooth muscle actin is transiently expressed in embryonic rat cardiac and skeletal muscles.
Actin isoform expression may change during development, and in certain physiological, experimental and pathological situations. It is accepted that during sarcomeric (skeletal and cardiac) muscle development, the alpha-skeletal and alpha-cardiac isoforms of actin accumulate rapidly at the onset of muscle fibre formation, while there is a rapid fall in the expression of nonmuscle (beta and gamma) actin isoforms. Here we show that, before birth, both skeletal and myocardial cells express significant amounts of alpha-smooth muscle actin mRNA and protein. This expression is transient and disappears over the 1-7 days following birth. Our findings show that the program regulating actin isoform expression in sarcomeric muscle development is complex and that alpha-smooth muscle actin participates in this process.
Actins↗
Efficiency and capacity of protein synthesis are increased in pressure overload cardiac hypertrophy.
We measured the rate of protein synthesis and total RNA content in the right ventricle (RV) at day 2 and day 4 after pulmonary artery constriction to determine the contributions of changes in capacity and efficiency of in vivo protein synthesis to pressure overload (PO) cardiac hypertrophy. A significant increase in the proportion of RV weight to total heart weight was observed at day 2 and day 4 when compared with untreated controls. The rate of protein synthesis was significantly higher at day 2 post-PO (0.31 +/- 0.06 day-1 or 30 +/- 5 mg.g RV-1.day-1, means +/- SD, P less than 0.05) as well as at day 4 (0.25 +/- 0.05 day-1 or 28 +/- 9 mg.g RV-1.day-1, P less than 0.05) than for untreated rabbits (0.15 +/- 0.03 day-1 or 17 +/- 4 mg.g RV-1.day-1). RNA content was significantly higher at day 2 (1.47 +/- 0.17 mg/g RV, P less than 0.05) than in controls (1.16 +/- 0.14 mg/g RV), whereas there was a slight but nonsignificant increase at day 4 (1.36 +/- 0.21 mg/g RV, P less than 0.1). The efficiency of protein synthesis (synthesis/RNA) per gram RV was significantly increased both at day 2 (20.5 +/- 2.2 g protein.g RNA-1.day-1, P less than 0.05) and day 4 (19.8 +/- 3.5 g protein.g RNA-1.day-1, P less than 0.05) compared with control (14.6 +/- 2.3 g protein.g RNA-1.day-1). The increase in efficiency appeared to be caused by pressure overload itself based on a comparison of 0-4 day data vs. data obtained from sham animals (P less than 0.05).
Animals↗
Bronchoalveolar lavage lipids during development of bleomycin-induced fibrosis in rats. Relationship to altered epithelial cell morphology.
Alterations in the structure and function of alveolar epithelial cells may contribute to the interstitial fibrosis that can develop following lung injury. The present studies were undertaken to determine if alterations observed in alveolar epithelial cell morphology and cytoskeletal composition are reflected in the profile of bronchoalveolar lavage (BAL) lipids recovered from injured lung. BAL protein and lipid analyses were performed on fluids recovered from control rats and from rats 7, 14, and 28 days after intratracheal instillation of bleomycin, an antineoplastic agent well-known to cause pulmonary interstitial fibrosis. There were increases in recovery of total protein, nonpolar lipid, polar lipid, and phospholipid following bleomycin treatment. The recovery of saturated phosphatidylcholine was increased, but recovery of a second surfactant phospholipid, phosphatidylglycerol, was unchanged, resulting in a significant change in their ratio. The recoveries of cholesterol, cholesterol ester, and triglyceride also were elevated. Changes in the proportional recoveries of neutral lipids, such as cholesterol and saturated phospholipids, could partly explain concurrent reductions in lung compliance that have been described. Changes in lavage lipids paralleled both the process of alveolar reepithelialization and altered expression of alveolar epithelial cell cytoskeletal proteins. Changes in lipid metabolism by alveolar epithelial cells following bleomycin-induced lung injury may be responsible for altered lavage lipid recovery and may directly be related to processes that take place during alveolar type II cell hyperplasia followed by transition to type I cells. BAL lipid analyses thus may provide a relatively noninvasive way of assessing these events.
Animals↗
Fractional synthesis rates in vivo of skeletal-muscle myosin isoenzymes.
The synthesis rates of different myosin isoenzymes in a single muscle, and of the same isoenzymes in different muscles (soleus, masseter and plantaris), were measured. The rate of total protein synthesis was significantly higher in the soleus [greater than 95% slow myosin (SM)] than in the plantaris [greater than 95% fast myosin (FM)]. Two fast isoenzymes, FM2 and FM3, were synthesized at different rates in the masseter, and SM was synthesized at a faster rate than FM. Intermediate myosin had a synthesis rate similar to that of FM. There was a small but significant difference between the synthesis rates of the SM isoenzymes of the soleus and masseter muscles. FM3 was synthesized faster in the masseter than in the plantaris, whereas FM2 was synthesized faster in the plantaris than in the masseter.
Animals↗
Intravenous amiodarone for malignant dysrhythmias of hypertrophic cardiomyopathy.
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Adolescent↗
Acute goiter hematoma following blunt neck trauma.
Traumatic hemorrhage into the thyroid gland is rarely reported. We report the case of a 30-year-old man who sustained blunt trauma to his neck, resulting in hemorrhage into a previously existing goiter. The patient's goiter was drained in the hospital. He was doing well at a three-month follow-up.
Accidental Falls↗
Lipids in bronchoalveolar lavage fluid from patients with sarcoidosis.
The recovery of protein and two specific surfactant lipids, phosphatidylcholine and phosphatidylglycerol, from bronchoalveolar lavage fluid is altered in chronic and acute non-granulomatous interstitial lung disease. This study set out to determine whether the same is true for patients with sarcoidosis. The median value for recovery of protein from lavage fluid was significantly higher in 21 patients with sarcoidosis than in 19 normal subjects (18 v 11 mg), while the median value for phospholipid recovery was significantly lower (4 v 1.7 mg). There were no changes in the proportions of phosphatidylcholine and phosphatidylglycerol. In addition, significantly less of the neutral lipid, cholesterol, was recovered (3.2 v 1.5 mg). The combined values of three biochemical measurements, non-phospholipid polar lipid, non-polar lipid, and protein, correctly classified all 40 subjects in our series; in a further group of nine normal subjects and 11 patients with sarcoidosis it allowed all but one normal subject to be classified correctly. These results are discussed in terms of alterations in epithelial cell function in interstitial disease.
Bronchoalveolar Lavage Fluid↗
Myosin isozyme synthesis and mRNA levels in pressure-overloaded rabbit hearts.
The in vivo synthesis rates of myosin isozyme heavy chains beta and alpha were measured in right ventricular (RV) muscle at 2 and 4 days following pulmonary artery constriction in rabbits, together with measurements of their relative mRNA levels. The synthesis rate of beta-myosin heavy chains was elevated in 2-day (0.27 +/- 0.06 day-1 or 2.5 +/- 0.7 mg/g RV/day, mean +/- SD) and in 4-day (0.25 +/- 0.08 day-1 or 2.8 +/- 1.0 mg/g RV/day) pressure overload, when compared to untreated rabbits (0.15 +/- 0.04 day-1 or 1.5 +/- 0.4 mg/g RV/day). However, the synthesis rates of alpha-myosin heavy chains in the same hearts were not altered significantly. There was a differential increase in the fractional synthesis rate of beta vs. alpha heavy chains in 2-day and 4-day pressure overload and in 2-day shams, suggesting switching toward beta heavy chain synthesis had occurred at these time points. beta heavy chain synthesis, as a proportion of total (alpha + beta) heavy chain synthesis, was significantly higher in 4-day pressure overload (78 +/- 9%) than in 4-day sham rabbits (63 +/- 6%). This increase in relative beta-synthesis was associated with a significant increase in the relative proportion of beta heavy chain mRNA level (76 +/- 13% vs. 56 +/- 7%). Furthermore, relative beta-synthesis and the beta-mRNA levels correlated linearly with each other in all experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Changes in skeletal-muscle myosin isoenzymes with hypertrophy and exercise.
The patterns of myosin isoenzymes in fast- and slow-twitch muscles of the rat hindlimb were studied, by pyrophosphate/polyacrylamide-gel electrophoresis, with hypertrophy (induced by synergist removal) and with spontaneous running exercise of 4 and 11 weeks duration. At 11 weeks, changes with hypertrophy in the slow-twitch soleus, composed of greater than 95% SM2 (slow myosin 2) in normal muscles, were minor, and consisted of an increase in the SM1 and SM1', and a loss of intermediate myosin (IM), an isoenzyme characteristic of Type IIa fibres [Fitzsimons & Hoh (1983) J. Physiol. (London) 343, 539-550]. The changes were dramatic, however, in the fast-twitch plantaris muscle. There was a 3-fold increase in the proportion of SM. In addition, IM became the predominant isoenzyme in the profile of hypertrophied plantaris by 4 weeks. These increases were balanced by decreases in the proportion of FM2 (fast myosin 2), with FM1 completely absent from the profile at 11 weeks. The changes in the plantaris with exercise were similar in direction but not as extensive as those with hypertrophy, and FM1 remained present at control levels throughout the study. When hypertrophy and exercise were combined, the increase in slow myosin was equal to the sum of the increases with each treatment alone. Changes at 4 weeks were intermediate between those of control and 11-week muscles. Peptide mapping of individual myosin isoenzymes showed that the heavy chains of IM were different from either fast or slow heavy chains. Furthermore, IM was found to be composed of a mixture of fast and slow light chains. These changes suggest that a transformation of myosin from fast to slow isoforms was in progress in the plantaris in response to hypertrophy, via a Type-IIa-myosin (IM) intermediate stage, a phenomenon similar to that occurring in chronically stimulated fast muscles during fast-to-slow transformation [Brown, Salmons & Whalen (1983) J. Biol. Chem. 258, 14686-14692].
Adenosine Triphosphatases↗
Preliminary report on the use of the Percluder occluding aortic balloon in human beings.
Management of massive exsanguinating hemorrhage is a major challenge in acute trauma care. The value of military antishock trousers (MAST) in this setting is controversial. In selected instances, thoracotomy with aortic cross-clamping may be effective and often is used as the "gold standard" to which new experimental therapy is compared. Previous animal research with an occluding aortic balloon catheter (Percluder) has shown this technique to be physiologically similar to aortic cross clamping. The Percluder was more effective than the MAST plus volume replacement in controlling hemorrhage and prolonging four-hour survival from blunt splenic trauma in an animal model. We have used the Percluder in 23 patients with life-threatening hemorrhage. There were 15 trauma cases, five cases of ruptured abdominal aortic aneurysm, and three others. Only nine of 23 patients (39%) had vital signs when the balloon was inserted; all showed an increase in arterial blood pressure of about 50% to 100% (P less than .0001). Two of 15 trauma victims (13%) and four aneurysm patients in whom the balloon was used were long-term survivors. One trauma victim lived for two weeks before dying of ischemic complications after 90 minutes of balloon aortic occlusion. Overall survival rate was 26%. This study was uncontrolled and occlusion therapy was not randomized. Eleven of 12 attempts to place the catheter by femoral cutdown were successful. Seven of 12 attempts (58%) to place the catheter percutaneously were successful. The six insertion failures were due to an inadequately small introducer, inability to identify arterial pulses in moribund patients, or difficulty in cannulating the femoral artery because of proximal occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Aortic Aneurysm↗
Keratin species in type II pneumocytes in culture and during lung injury.
A detailed understanding of alveolar epithelial cell transitions during remodeling after lung injury requires the identification of specific markers. We have developed a panel of monoclonal antibodies against species of the intermediate filament protein, keratin. These individual species are recognized markers of the state of differentiation of various epithelial cells. These and complementary protein analytic methods have been applied to studies of isolated, enriched Type II pneumocyte preparations as well as to normal and injured lung tissues. Monoclonal antibody 24A3, initially raised against Morris hepatoma 7777 keratins, decorated a filament network in isolated cultured rat Type II pneumocytes by indirect immunofluorescence; it reacts by 2-dimensional polyacrylamide gel immunoblot procedures with an acidic, 46,000-dalton keratin. Monoclonal antikeratin antibodies AE1 and AE3, raised against human epidermal keratins, reacted poorly with isolated Type II cells; however, AE3 reacted by immunoblot technique with the 55,000-dalton keratin subclass. The bronchial epithelium reacted intensely with 24A3 as well as with a mix of AE1 plus AE3 in ethanol-fixed, paraffin-embedded sections of normal and injured rat lung. Alveolar regions of normal lung reacted poorly with all 3 antibodies, however, as visualized by light microscopy. At the same time, very large, presumptive epithelial cells in the alveolar regions stained intensely with 24A3 3 days after intratracheal instillation of bleomycin, whereas thin cells lining the alveoli in injured regions were intensely reactive 14 days after bleomycin treatment. These elongated cells may represent Type II pneumocytes in the process of converting to Type I cells.
Animals↗
Comparison of the use of isotopic proline vs leucine to measure protein synthesis in cultured fibroblasts.
Compartmentation of the amino acid precursor pools for protein synthesis in cultured cells can substantially complicate measurements of synthesis rates. This is particularly true for nonessential amino acids such as proline, an amino acid often used in isotopic form to measure collagen synthesis. We have made a comparative study of this problem in cultured IMR-90 fibroblasts using isotopic proline and leucine to measure total protein and collagen synthesis. 3H-leucine in the extracellular (EC) medium equilibrates with tRNA-leucine at an EC concentration of 0.4 mM in both dividing and stationary cells. Thus, under these experimental conditions there is no complicating compartmentation of leucine for protein synthesis. Equilibration of EC and tRNA-bound 3H-proline, however, does not occur even when the EC concentration is in the mM range, based upon simultaneous measurements of synthesis rates using 3H-proline and 3H-leucine together. Furthermore, significant changes in EC proline concentration and specific activity occur over short time intervals (2 hr) if the initial EC proline concentration is below 0.2 mM. Thus, the use of isotopic proline to measure protein synthesis introduces substantial interpretive problems. Serum deprivation causes changes in both total collagen synthesis and the percent of protein synthesis devoted to collagen when measured with either 14C-leucine or 3H-proline. At the same time, isotopic proline remains the better choice for measuring percent collagen synthesis.
Carbon Radioisotopes↗
Insulin sensitivity and responsiveness of epitrochlearis and soleus muscles from fed and starved rats. Recognition of differential changes in insulin sensitivities of protein synthesis and glucose incorporation into glycogen.
The insulin sensitivity of protein synthesis and glucose incorporation into glycogen by the soleus and epitrochlearis muscles from fed rats and 24 h-starved rats was determined in vitro during the first and second hours of incubation after isolation of the muscles. Rates of protein synthesis by both muscles from fed rats in the first hour of incubation were 2-fold higher than in the second hour and were not increased by insulin. Rates of protein synthesis during the first hour in the presence of 6000 microunits of insulin/ml were increased in soleus, but not in epitrochlearis, muscles from starved rats. Rates of protein synthesis in both muscles from fed and starved rats were increased significantly by insulin during the second hour. High concentrations of insulin caused a marked stimulation of the rates of glucose incorporation by both muscles from fed and starved rats in both the first and second hours of incubation. The insulin sensitivity of glucose incorporation during the second hour, defined as the concentration of insulin causing half-maximal stimulation, was increased 10-fold for both muscle types from starved rats (soleus, 65 microunits/ml; epitrochlearis, 45 microunits/ml) relative to muscles from fed rats (soleus, 600 microunits/ml; epitrochlearis, 500 microunits/m). The insulin sensitivity of protein synthesis in the second hour was greater for soleus muscles from starved rats (65 microunits/ml) than from fed rats (500 microunits/ml). In contrast, the insulin sensitivity of protein synthesis in epitrochlearis muscles from starved rats was significantly decreased (225 microunits/ml) compared with fed rats (25 microunits/ml Maximal rates achieved by high concentrations of insulin were not different from those in the same muscle from fed rats. It is suggested that protein synthesis, in distinction to glucose utilization, may be resistant to insulin stimulation during periods of acute starvation in muscles with fibre compositions similar to the epitrochlearis, but not in muscles with fibre compositions similar to the soleus. Partial reversal of the resistance observed in vitro for epitrochlearis muscles from starved rats may be due to the loss of factors which suppress the effect of insulin in vivo.
Animals↗