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J M Snyder

Publications and source records attributed to J M Snyder.

At least 19 recordsLinked to original sources
PubMed1995

Characterization of alpha 1, beta 1, and gamma 1 laminin subunits during rabbit fetal lung development.

Laminin-1 is an extracellular matrix protein composed of three polypeptide chains that are designated alpha 1, beta 1, and gamma 1. We investigated the expression of laminin alpha 1, beta 1, and gamma 1 subunit chains during several stages of rabbit fetal lung development. Utilizing polyclonal antibodies directed against human placental laminin and immunoblot analysis, we found that the highest levels of laminin alpha 1, beta 1, and gamma 1 subunit chains in the fetal lung were present on day 26 of gestation (term = 31 days), coincident with the initiation of alveolar epithelial cell differentiation. Levels of the laminin chains were approximately five times higher in fetal lung at day 26 of gestation than in adult lung tissue. Different temporal patterns of laminin alpha 1, beta 1, and gamma 1 subunit chain expression were observed, data suggestive that the chains are independently regulated during lung development. Laminin was localized to the basement membranes of bronchi, bronchioles, prealveolar ducts, and blood vessels in fetal lung tissue, as shown by immunostaining with polyclonal laminin antibodies. A similar staining pattern was observed in adult lung tissue, but the alveolar wall was also stained. Laminin was also observed surrounding a few mesenchymal cells in fetal lung on day 19 of gestation; the number of positive mesenchymal cells increased with lung development. Laminin alpha 1 subunit chains, detected using a monoclonal antibody, were present in the basement membranes of bronchi, bronchioles, prealveolar ducts, and blood vessels in fetal lung tissue. No laminin alpha 1 chain staining was observed in the mesenchyme of early fetal lung tissue. Using a monoclonal antibody, laminin beta 1 subunit chains were immunolocalized in the basement membranes of bronchi, bronchioles, in prealveolar ducts, and surrounding some mesenchymal cells in fetal lung tissue. Laminin alpha 1 and beta 1 subunit chains in adult lung tissue were present in basement membranes of airways, blood vessels, and alveoli. Thus, changes in the localization and accumulation of laminin near the time of alveolar type I and type II epithelial cell differentiation suggest that laminin may play a role in mediating the differentiation of these cell types during rabbit fetal lung development.

Animals↗
PubMed1993

Glucocorticoid regulation of surfactant-associated proteins in rabbit fetal lung in vivo.

The effects of a maternally administered synthetic glucocorticoid, betamethasone, on the levels of mRNA for the surfactant proteins SP-A, SP-B, and SP-C and on the levels of SP-A protein were investigated in day 27 gestational age rabbit fetal lung tissue. Betamethasone administration to the pregnant rabbit caused approximately a twofold increase in the fetal lung level of SP-A protein and a threefold increase in fetal lung SP-A mRNA levels when compared to levels in fetuses obtained from saline-treated or uninjected animals. SP-B mRNA was increased fourfold in fetal lung tissue obtained from glucocorticoid-treated pregnant does when compared to levels in fetuses of uninjected pregnant does. However, SP-B mRNA levels in fetal lung tissue from saline-injected controls were also significantly elevated, approximately twofold, when compared to fetal lung SP-B mRNA levels in the uninjected control condition. SP-C mRNA levels in lung tissue of fetuses from both saline-injected and betamethasone-injected pregnant does were increased similarly, approximately twofold, over SP-C mRNA levels in fetal lung tissue obtained from uninjected control does. These data are suggestive that betamethasone treatment increases fetal lung SP-A and SP-B mRNA levels and that maternal stress alone can increase the expression of SP-B and SP-C mRNA in rabbit fetal lung tissue. Using in situ hybridization, SP-A mRNA was shown to be present primarily in alveolar type II cells in fetuses of control and saline-injected does. However, SP-A mRNA was easily detected in both alveolar type II cells and bronchiolar epithelial cells of rabbit fetal lung tissue following maternal betamethasone treatment. In contrast, SP-B and SP-C mRNA were present only in alveolar type II cells of lung tissue obtained from fetuses of control, saline, or betamethasone-treated does. Thus maternal administration of glucocorticoids increased SP-A protein as well as SP-A and SP-B mRNA levels in rabbit fetal lung tissue. SP-A mRNA was localized to both alveolar type II cells and in smaller amounts in bronchiolar epithelial cells of rabbit fetal lung tissue. However, SP-B and SP-C mRNA were detected only in alveolar type II cells.

Animals↗
PubMed1993

Oxygen modulates the differentiation of human fetal lung in vitro and its responsiveness to cAMP.

Previously, it was found that lung explants from mid-trimester human abortuses differentiate spontaneously in organ culture in serum-free defined medium in an atmosphere of 95% air-5% CO2. Dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) treatment of human fetal lung in culture increases the rate of morphological differentiation and enhances expression of the surfactant protein A (SP-A) gene. To begin to define the factors responsible for this accelerated in vitro differentiation, we analyzed the effects of atmospheric oxygen on the morphological and biochemical development of human fetal lung in culture and on responsiveness of the cultured tissue to DBcAMP. We found that when lung explants were maintained in an atmosphere containing 1% oxygen they failed to differentiate spontaneously and no induction of SP-A gene expression was apparent. Furthermore, at 1% oxygen, DBcAMP had no effect to stimulate morphological differentiation or SP-A gene expression. When lung tissues that had been maintained for 5 days in 1% oxygen were transferred to an environment containing 20% oxygen, there was rapid morphological development and induction of SP-A gene expression. The effects on morphological development were manifest within 24 h of transfer to the 20% oxygen environment; within 72 h, a marked stimulatory effect of DBcAMP on SP-A gene expression also was observed. Our findings further suggest that the effects of oxygen on the levels of SP-A and SP-A mRNA are concentration dependent. Interestingly, the inductive effects of DBcAMP on SP-A gene expression were apparent only at oxygen concentrations > or = 10%. Morphological differentiation of the cultured human fetal lung tissue also was influenced by oxygen in a concentration-dependent manner. These findings suggest that oxygen plays an important permissive role in the spontaneous differentiation of human fetal lung in vitro.

Bucladesine↗
PubMed1993

Diuretic and diet effect on Menière's disease evaluated by the 1985 Committee on Hearing and Equilibrium guidelines.

Fifty-four patients, diagnosed with Menière's disease and treated with diuretics and a low-salt diet, were evaluated retrospectively with the 1985 AAO/HNS Committee on Hearing and Equilibrium (CHE) guidelines for vertigo and hearing changes. The patient data base was also evaluated with other methods that helped determine the effectiveness of the 1985 AAO/HNS CHE guidelines. After 24 months of therapy, vertigo control was complete or substantial in 79% of the patients, limited or insignificant in 19%, and worse in 2% as evaluated by the CHE 1985 guidelines. Hearing improved in 35% of the patients, was unchanged in 29%, was worse in 22%, and could not be classified by CHE guidelines in 14%. Hearing was also evaluated by comparison of individual thresholds before medical therapy, and at 22 and 74 months after the start of medical therapy. We found a stabilization of low- and mid-threshold frequencies, with an average rate of hearing loss approximating 0 dB/yr with 74 months of followup. The results of this preliminary study suggest that diuretics and a low-salt diet may decrease the natural progression of sensorineural hearing loss in patients with Menière's disease. Compared with other methods of data analysis, the 1985 CHE guidelines lacked sensitivity to evaluate the hearing changes observed.

Academies and Institutes↗
PubMed1993

Retinoic acid differentially regulates expression of surfactant-associated proteins in human fetal lung.

Retinoic acid is known to play an essential role in maintaining the differentiation of a wide variety of epithelial cell types. However, its effects on the differentiation of lung alveolar epithelium have not been described. In the present study, we examined the effects of retinoic acid on the differentiation of human fetal lung tissue maintained in vitro. Human fetal lung explants were cultured in serum-free medium for 6 days in the absence or presence of all-trans retinoic acid at concentrations from 0.3 nM to 3 microM. Explant content of the surfactant-associated protein SP-A was measured using a specific enzyme-linked immunosorbent assay. Retinoic acid reduced SP-A protein levels in a concentration-dependent manner [analysis of variance (ANOVA), P < 0.01]. To evaluate possible cytotoxic effects of retinoic acid, culture media were assayed for lactate dehydrogenase (LDH), a cytoplasmic enzyme. LDH levels in media from retinoic acid-treated explants were not significantly different than LDH levels in media from control explants, indicating that retinoic acid is not cytotoxic in human fetal lung explants. Changes in messenger RNA (mRNA) levels for surfactant-associated proteins SP-A, SP-B, and SP-C were measured by Northern blot analysis. Retinoic acid reduced SP-A mRNA levels in a concentration-dependent manner (ANOVA, P < 0.02) and reduced SP-C mRNA levels at 3 microM. In contrast, retinoic acid increased SP-B mRNA levels in a concentration-dependent manner (ANOVA, P < 0.03). Morphometric analysis showed that retinoic acid decreased epithelial volume density in the explants by approximately 17% and increased connective tissue volume density by approximately 20% when compared to dimethyl sulfoxide vehicle controls. These data indicate that retinoic acid regulates type II cell surfactant protein gene expression in human fetal lung tissue.

Blotting, Northern↗
PubMed1992

Glucocorticoid effects on rabbit fetal lung maturation in vivo: an ultrastructural morphometric study.

Maternal administration of glucocorticoids is known to stimulate fetal lung maturation. In the present study, we used microscopy and stereology to evaluate the morphological effects of maternal glucocorticoid treatment on rabbit fetal lung tissue. Betamethasone was administered to pregnant rabbits on days 25 and 26 of gestation at a dose of 0.2 mg/kg body weight. The animals were sacrificed on day 27 of gestation. Glucocorticoid treatment significantly increased the presumptive airspace in the fetal lung tissue but did not alter the relative proportion of epithelium, connective tissue, or vasculature in the tissue. In addition, glucocorticoid treatment significantly increased the proportion of type II cells in the prealveolar epithelium, increased the rate of phosphatidylcholine synthesis, and increased the content of the major surfactant-associated protein, SP-A, in the fetal lung tissue. We could detect no effect of betamethasone on lamellar body cross-sectional area, numerical density, or volume density within fetal lung type II cells. Glucocorticoid treatment of the pregnant doe caused a decrease in the volume density of intracellular glycogen and an increase in the volume density of mitochondria in fetal lung type II cells. Betamethasone treatment did not alter the distance between fetal lung epithelial cells and subadjacent connective tissue cells. However, glucocorticoid treatment increased the number of connective tissue foot processes that pierced the epithelial basal lamina. Thus, glucocorticoid treatment of the pregnant doe results in structural changes in the fetal lung tissue, an acceleration of some aspects of type II cell differentiation, and a concomitant increase in epithelial-mesenchymal interactions.

Animals↗
PubMed1992

Localization of surfactant-associated protein C (SP-C) mRNA in fetal rabbit lung tissue by in situ hybridization.

Surfactant is a lipoprotein substance that is synthesized and secreted by alveolar type II epithelial cells and acts to reduce surface tension at the air-alveolar interface. SP-C is a 5,000-D molecular weight, hydrophobic, surfactant-associated protein. In the present study, we used a ribonuclease protection assay to show that SP-C mRNA is induced in rabbit fetal lung tissue early in development, increases in relative concentration as development proceeds, and is present in maximal concentration at term (31 days of gestation). We also used the technique of in situ hybridization to localize SP-C mRNA in fetal, neonatal, and adult rabbit lung tissue. SP-C mRNA was present in all of the epithelial cells of the prealveolar region of day 19 gestational age rabbit fetal lung tissue, i.e., about 7 days before the appearance of differentiated alveolar type II cells in the fetal lung tissue. By day 27 of gestation, SP-C mRNA was restricted to epithelial cells with the morphologic characteristics of alveolar type II cells. SP-C mRNA was not detected in bronchiolar epithelium at any stage of lung development. The intensity of SP-C mRNA hybridization in the prealveolar and alveolar type II epithelial cells increased as a function of gestational age and was maximal at term. The pattern of SP-C mRNA localization in neonatal and adult rabbit lung tissue was consistent with the restriction of SP-C gene expression to differentiated alveolar type II cells. Our data are suggestive that SP-C may serve some as yet unknown function early in lung development because it is present in fetal lung prealveolar epithelial cells much earlier in gestation than are differentiated, surfactant-producing alveolar type II cells.

Aging↗
PubMed1992

Localization of surfactant-associated proteins SP-A and SP-B mRNA in rabbit fetal lung tissue by in situ hybridization.

Pulmonary surfactant is a lipoprotein substance, comprised of approximately 80% phospholipid and approximately 10% protein, that lowers surface tension at the air-alveolar aqueous interface. Surfactant is synthesized and secreted by alveolar type II epithelial cells where it is stored intracellularly in lamellar bodies. In the present study, we used the technique of in situ hybridization to localize the mRNA for two surfactant-associated proteins, SP-A and SP-B, in developing rabbit fetal lung tissue. We found that SP-A mRNA was first localized in rabbit fetal lung alveolar type II cells on day 26 of gestation, the time at which lamellar bodies are first observed within fetal lung type II cells. On day 28 of gestation, a very small amount of SP-A mRNA was also detectable in the epithelial cells of some bronchioles. In neonatal and adult rabbit lung tissue, SP-A mRNA was primarily restricted to alveolar type II cells; however, the epithelial cells of some bronchioles contained small amounts of SP-A mRNA. SP-B mRNA was first detected in cuboidal epithelial cells in the prealveolar region of the rabbit fetal lung tissue on day 24 of gestation, i.e., at least 2 days before the appearance of SP-A mRNA and lamellar bodies within differentiated alveolar type II cells. SP-B mRNA was detected in most bronchiolar epithelial cells of the rabbit fetal lung tissue at day 28 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Localization of cystic fibrosis transmembrane conductance regulator mRNA in human fetal lung tissue by in situ hybridization.

The fetal pulmonary epithelium secretes fluid. Cl transport is presumed to provide the driving force for net fluid secretion, although the cellular mechanisms have not been well identified in the fetus. The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP- and nucleoside triphosphate-regulated Cl channel; mutations in CFTR cause cystic fibrosis. We hypothesized that if CFTR is involved in fetal lung fluid transport, the fetal pulmonary epithelium should express CFTR mRNA. We used the technique of in situ hybridization with 3H-anti-sense and, as a control, 3H-sense CFTR cRNA probes to localize CFTR mRNA in human fetal lung tissue and cultured lung explants and determine when in gestation it is expressed. Epithelial cells of both first and second trimester lung tissues expressed CFTR mRNA. A decreasing gradient of CFTR mRNA expression was present from the proximal to the distal pulmonary epithelium. Cultured second trimester lung tissue explants expressed more CFTR mRNA than the uncultured starting tissue, suggesting CFTR gene expression increased during the five days in culture. Furthermore, alveolar type II cells in cultured explants expressed CFTR mRNA, suggesting that these cells are Cl-secretory and may be involved in lung fluid transport. These data confirm that CFTR mRNA is expressed in the human fetal pulmonary epithelium, consistent with the Cl-secretory properties of the fetal lung.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed1992

Insulin regulation of messenger ribonucleic acid for the surfactant-associated proteins in human fetal lung in vitro.

Respiratory distress syndrome (RDS) is primarily caused by an immaturity in the synthesis and secretion of surfactant by the fetal lung type II cell. Fetal hyperinsulinemia associated with maternal diabetes places the newborn at an increased risk of developing RDS, and therefore, it has been hypothesized that insulin inhibits type II cell differentiation. We have previously shown that insulin inhibits the accumulation of surfactant-associated protein A (SP-A), the major surfactant-associated protein, in human fetal lung explants maintained in vitro. In the present study, we used Northern blot analysis to evaluate the effects of insulin on the content of SP-A messenger RNA (mRNA) as well as on the content of mRNA for the hydrophobic surfactant-associated proteins SP-B and SP-C in human fetal lung explants maintained in vitro. Lung explants were maintained in serum-free medium with or without added insulin (0.25-2500 ng/ml) for up to 6 days. We observed that insulin, at concentrations of 25-2500 ng/ml, significantly inhibited the accumulation of SP-A mRNA when compared to controls (P less than 0.01). The inhibitory effect of insulin on SP-A mRNA accumulation was dose dependent with an approximately 75% inhibition observed at 2500 ng/ml. Insulin, at the concentration of 2500 ng/ml, significantly inhibited the accumulation of SP-B mRNA by approximately 30% when compared to control levels (P less than 0.01) but had no effect at lower concentrations. Insulin had no significant effect on SP-C mRNA levels at any concentration tested. Our findings provide evidence that insulin may delay fetal lung development by inhibiting SP-A and SP-B gene expression. A deficiency of these proteins in pulmonary surfactant may account for the increased incidence of RDS in infants of diabetic mothers.

Blotting, Northern↗
PubMed1992

Factors influencing ototoxicity in ovarian cancer patients treated with Cis-platinum based chemotherapy.

Seventy-seven ovarian cancer patients were evaluated for auditory toxicity following low-dose, slow-infusion cisplatin therapy. Twenty patients had baseline normal hearing with conventional audiological assessment of pure tone sensitivity at 250 to 8,000 Hz prior to therapy, along with at least one repeated audiogram before subsequent treatments. Ten of these patients also had serial assessment of ultra-high frequencies (10,000 to 18,000 Hz). Six of the 20 patients (30%) developed pure tone threshold elevations of at least 10 dB in any two frequencies. This hearing loss was predominantly persistent, bilateral, symmetrical, and above the speech range. Hearing loss was categorically mild and not statistically significant, at any specific frequencies. Hearing loses were not progressive with repeated doses of cisplatin. Only one of 20 patients reported tinnitus, and no vestibular toxicity was observed. One patient complained of clinically significant hearing difficulty. The risk of developing hearing loss appeared significant for patients older than 42 years, but failed to correlate statistically with disease stage at diagnosis, cumulative cisplatin dosage, or the presence of other ototoxic drugs (furosemide and IV aminoglycosides). The relationship between nephrotoxicity and ototoxicity in this study was inconclusive.

Adolescent↗
PubMed1991

An ultrastructural, morphometric analysis of rabbit fetal lung type II cell differentiation in vivo.

Rabbit lung type II cell differentiation was evaluated by use of ultrastructural, morphometric techniques. Fetal lung epithelial cells decreased in size dramatically from day 19 to day 21 of gestation. Thereafter, the cell and cytoplasmic cross-sectional area declined gradually until the neonatal time point. The tall columnar cell shape characteristic of fetal lung epithelial cells at early stages of development became cuboidal by day 24 of gestation. The number of mitochondria per micron2 cytoplasmic area in presumptive alveolar epithelial cells and the mitochondrial volume density increased toward the end of gestation. The volume density of glycogen pools within fetal lung epithelial cells reached a plateau on day 21 of gestation and then declined sharply on day 26 of gestation in lamellar body-containing, type II epithelial cells. Lamellar bodies increased in number and volume density in epithelial cells starting on day 26 of gestation and peaked with respect to these parameters in the neonatal lung tissue. Multivesicular bodies, which are thought to be a precursor to the lamellar body, became more prominent in differentiated type II cells on day 26 of gestation and increased in volume density from day 28 of gestation to the adult time point. The distance between mesenchymal and epithelial cells in fetal lung tissue declined sharply between days 24 and 26 of gestation but remained relatively constant thereafter. Foot processes extending from connective tissue cells contiguous to the epithelium were generally more numerous than those extending from the basal plasma membrane of epithelial cells at every stage of development examined. These data quantitate for the first time key ultrastructural events that occur during the differentiation of fetal lung epithelial cells in vivo.

Animals↗
PubMed1990

Peroxisome proliferation and induction of peroxisomal enzymes in mouse and rat liver by dehydroepiandrosterone feeding.

Dehydroepiandrosterone (DHEA) treatment is effective in the prevention of various genetic and induced disorders of mice and rats. In studies designed to define some of the basic mechanisms that underline the beneficial chemopreventive effects exerted by the action of this steroid, we found that the liver undergoes profound changes that result in: (i) hepatomegaly; (ii) color change from pink to mahogany; (iii) proliferation of peroxisomes; (iv) increased cross-sectional area and volume density of peroxisomes; (v) increased or decreased number of mitochondria per cell; (vi) decreased mitochondrial cross-sectional area; (vii) marked induction of the peroxisomal bifunctional protein enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase; (viii) increased activities of enoyl-CoA hydratase and other peroxisomal enzymes assayed in this study, viz. catalase, carnitine acetyl-CoA transferase, carnitine octanoyl-CoA transferase, and urate oxidase; and (ix) increased activity of mitochondrial carnitine palmitoyl-CoA transferase. In addition, feeding DHEA to mice resulted in increased plasma cholesterol levels in two strains of mice evaluated in this study, and either slightly decreased or markedly increased plasma triglyceride levels, depending on the strain. Whether liver peroxisome proliferation, induced by DHEA feeding to mice and rats, plays a role in the chemopreventive effects elicited by this steroid remains to be established.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1990

Prostaglandins regulate surfactant protein A (SP-A) gene expression in human fetal lung in vitro.

We previously have observed that dexamethasone has a biphasic effect on surfactant protein A (SP-A) mRNA levels in human fetal lung in vitro. At concentrations of 10(-10)-10(-9) M, dexamethasone increases the levels of SP-A mRNA, whereas, at concentrations greater than 10(-8) M, the steroid is markedly inhibitory. In studies to define the molecular mechanisms for these effects, we observed that dexamethasone causes a dose-dependent stimulation of SP-A gene transcription, but paradoxically causes a dose-dependent inhibition of SP-A mRNA stability. In light of the well-characterized inhibitory effect of glucocorticoids on prostaglandin (PG) synthesis in a number of tissues, it was our objective in the present study to investigate the role of PGs on SP-A gene expression in human fetal lung in vitro and to determine whether the action of dexamethasone (greater than 10(-8) M) to reduce SP-A mRNA levels could be mediated by its effect to inhibit PG synthesis. We found that dexamethasone 10(-7) M) caused a marked decrease in the secreted levels of the PGE2 and PGF2 alpha, the prostacyclin metabolite, 6-keto-PGF1 alpha, and the thromboxane A2 metabolite, thromboxane B2. Indomethacin, which also caused a pronounced reduction in the levels of these secreted prostanoids, had a marked effect to reduce SP-A mRNA levels in human fetal lung in vitro. The inhibitory effects of indomethacin were associated with an 73% reduction in cAMP formation by the fetal lung in culture, and were prevented by simultaneous incubation with dibutyryl cAMP or with PGE2. PGE2 markedly increased cAMP formation by the human fetal lung tissue incubated in the absence or presence of indomethacin. Inhibitory effects of dexamethasone and indomethacin also were observed on two morphological indices of lung differentiation, alveolar lumenal volume density, and lamellar body volume density. PGE2 significantly increased lumenal volume density of the human fetal lung explants. The finding that the inhibitory action of dexamethasone (10(-7) M) on SP-A mRNA levels could not be prevented by simultaneous incubation with either PGE2 or dibutyryl cAMP and that dexamethasone had no apparent effect on cAMP formation by the fetal lung in vitro is suggestive that the action of dexamethasone (greater than or equal to 10(-8) M) to reduce SP-A mRNA levels is mediated at least in part by actions alternative to its inhibitory effects on PG synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Uptake of the 35 kDa major surfactant apoprotein (SP-A) by neonatal rabbit lung tissue.

Secreted surfactant is made up of both phospholipid and protein components. Therefore, we investigated the possibility that surfactant apoproteins might be taken up by the alveolar type II cell in a manner similar to the uptake of surfactant phosphatidylcholines. Day 2 neonatal rabbits were infused via the trachea with a solution of carrier surfactant and 125I-labelled surfactant apoprotein (SP-A, Mr approx. 35,000). Most of the 125I-SP-A remained within the alveolus; however, a fraction of the 125I-SP-A was taken up by the lung tissue from the alveolus in a time-dependent manner. The small amount of radiolabeled material detected in blood, liver or kidney tissues of 125I-SP-A-infused animals was not trichloroacetic acid (TCA) precipitable, i.e., probably represented degradation products. In contrast, the proportion of TCA-precipitable 125I-SP-A in lung tissue or lavage samples did not change as function of time after tracheal administration. Two-dimensional gel electrophoresis of the 125I-SP-A present in the lavage samples or associated with lung tissue was used to show that a small proportion of the 125I-SP-A was partially degraded in the lung tissue and alveolus. These data are suggestive that the SP-A is taken up by lung tissue, perhaps in a manner similar to the uptake of surfactant phospholipid by the alveolar type II cell.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1988

The concentration of the 35-kDa surfactant apoprotein in amniotic fluid from normal and diabetic pregnancies.

A specific, enzyme-linked immunoabsorbent assay was used to determine the concentration of the 35,000 mol wt surfactant apoprotein (SP-A) in samples of amniotic fluid obtained from nondiabetic (n = 358) and diabetic (n = 29) women. The enzyme-linked immunoabsorbent assay was performed with rabbit antibodies directed against SP-A present in lavage fluid from a patient with alveolar proteinosis. Amniotic fluid SP-A concentrations increased as a function of gestational age, from less than 3 micrograms/ml at 30-31 wk to 24 micrograms/ml at 40-41 wk, and were positively correlated with the lecithin to sphingomyelin ratio (p less than 0.01). SP-A concentrations also increased as a function of gestational age in shake test positive samples (p less than 0.05), but were unchanged in shake test-negative samples. There was no difference in the surfactant apoprotein concentration of male compared with female fetuses at any gestational age. In amniotic fluid obtained from 20 diabetic women, SP-A levels were significantly less than in nondiabetic pregnancies that were matched for gestational age and sex of the fetus (p less than 0.05). The SP-A concentrations in amniotic fluids obtained from nine women who were diabetic and hypertensive and from 10 hypertensive women were not different from matched controls. The relationships described above were valid whether the SP-A concentration was expressed per mg protein or per ml amniotic fluid. These data are suggestive that the concentration of amniotic fluid SP-A is decreased in diabetic pregnancies.

Amniotic Fluid↗
PubMed1988

Glucocorticoid regulation of the major surfactant associated protein (SP-A) and its messenger ribonucleic acid and of morphological development of human fetal lung in vitro.

In the present study we investigated the effects of dexamethasone (DEX) on the accumulation of the major pulmonary surfactant-associated protein (SP-A), a glycoprotein of about 35,000 mol wt, and on the levels of mRNA encoding this protein in human fetal lung in organ culture. In addition, the effects of DEX on the structural development of the fetal lung tissue was investigated using morphometric techniques. We observed that DEX had a biphasic effect on the accumulation of SP-A and its mRNA; at concentrations of 10(-10) and 10(-9) M, a stimulatory effect was observed, while at concentrations of 10(-8) M or greater, the glucocorticoid was markedly inhibitory. The inhibitory effect of DEX (10(-7) M) was evident at all time points of incubation and was apparent within 24 h of its addition to the medium at any time during the culture period. In addition, DEX (10(-7) M) antagonized the stimulatory effects of (Bu)2cAMP on the accumulation of SP-A and its mRNA. DEX also had pronounced effects on the morphological development of human fetal lung tissue. At a concentration of 10(-7) M or greater, DEX caused a marked reduction of alveolar lumen size compared to that of fetal lung explants maintained in control medium. A biphasic effect of DEX on the volume density of type II cells in fetal lung explants was observed; at a concentration of 10(-10) M, DEX significantly increased the volume density of type II cells, whereas at a concentration of 10(-7) M or more, the glucocorticoid significantly reduced the volume density of type II cells compared to that of control explants. These findings suggest that synthetic glucocorticoids at concentrations of 10(-10) and 10(-9) M are stimulatory whereas elevated levels are inhibitory of SP-A synthesis and morphological development of the human fetal lung.

Bucladesine↗