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Biomedical subjects

R A Sinkin

Publications and source records attributed to R A Sinkin.

At least 19 recordsLinked to original sources
PubMed2001

Improving cognitive development of low-birth-weight premature infants with the COPE program: a pilot study of the benefit of early NICU intervention with mothers.

The purpose of this pilot study was to evaluate the effectiveness of a parent-focused intervention program (COPE) on infant cognitive development and maternal coping. A randomized clinical trial was conducted with 42 mothers of low-birth-weight (LBW) premature infants hospitalized in a neonatal intensive care unit (NICU), with follow-up at 3 months' and 6 months' corrected ages. COPE mothers received the four-phase educational-behavioral program that began 2-4 days postbirth and continued through 1 week following discharge from the NICU. Comparison mothers received audiotaped information during the same four time frames. Results indicated that COPE infants had significantly higher mental development scores at a 3 months' corrected age (M = 100.3) than did the comparison infants (M = 93.9), and this difference widened at 6 months' corrected age, with COPE infants scoring 14 points higher. COPE mothers were significantly less stressed by the NICU sights and sounds and had significantly stronger beliefs about what behaviors and characteristics to expect from their premature infants. Findings from this study support the need for further testing of early NICU interventions with parents to determine their effectiveness on parental coping and infant developmental outcomes.

Adaptation, Psychological↗
PubMed2000

Early dexamethasone-attempting to prevent chronic lung disease.

BACKGROUND: We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome. (1) A multicenter, randomized, double-blind trial was undertaken to confirm these results. METHODS: Infants <30 weeks' gestation were eligible if they had respiratory distress syndrome, required mechanical ventilation at 12 to 18 hours of age, and had received at least 1 dose of exogenous surfactant. Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present. A total of 384 infants were enrolled-189 randomized to dexamethasone (.5mg/kg birth weight at 12-18 hours of age and a second dose 12 hours later) and 195 to an equal volume of saline placebo. RESULTS: No differences were found in the dexamethasone versus placebo groups, respectively, regarding the primary outcomes of survival (79% vs 83%), survival without oxygen at 36 weeks' corrected gestational age (CGA; both 59%), and survival without oxygen at 36 weeks' CGA and without late glucocorticoid therapy (46% vs 44%). No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen (50 vs 56 days), ventilation (20 vs 27 days), days to regain birth weight (15.5 vs 14 days), or length of stay (LOS; 88 vs 89 days). Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization (27% vs 35%). No clinically significant side effects were noted in the dexamethasone group, although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10. Among infants who died (40 vs 33), there were no differences in the median days on oxygen, ventilation, nor LOS. However, in survivors (149 vs 162), the following were observed: median days on oxygen 37 versus 45 days, ventilation 14 versus 19 days, and LOS 79 versus 81 days, for the dexamethasone versus placebo groups, respectively. CONCLUSIONS: This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks' CGA and survival was not improved. However, early dexamethasone reduced the use of later prolonged dexamethasone therapy, and among survivors, reduced the median days on oxygen and ventilation. We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗
PubMed2000

Respiratory syncytial virus and premature infants born at 32 weeks' gestation or earlier: hospitalization and economic implications of prophylaxis.

OBJECTIVES: To assess the risk of hospitalization associated with respiratory syncytial virus (RSV) and to estimate the economic impact of RSV prophylaxis with either RSV immune globulin (RSV-Ig) or RSV monoclonal antibody (palivizumab) on a cohort of preterm infants born at 32 weeks' gestation or earlier. DESIGN: Historical cohort study. SETTING: A 12-county neonatal network served by the regional center in Rochester, NY. PARTICIPANTS: One thousand twenty-nine infants born at 32 weeks' gestation or earlier followed up until 1 year of corrected age. MAIN OUTCOME MEASURES: Rate of hospitalization with an RSV-associated illness; cost per hospitalization prevented resulting from either form of RSV prophylaxis. RESULTS: The probability of hospitalization with an RSV-associated illness for infants born at 32 weeks' gestation or earlier was estimated at 11.2%. The incidence of RSV hospitalization increased with decreasing gestational age (13.9% vs 4.4% for infants born at < or =26 weeks' gestation vs those born at 30-32 weeks' gestation). Infants requiring respiratory support at 36 weeks of postconceptual age (PCA) or older had a higher hospitalization rate (16.8% vs 6.2%), longer hospital stays, and higher hospital charges than infants requiring respiratory support at less than 36 weeks of PCA. For infants requiring respiratory support at less than 36 weeks of PCA, the incidence of RSV hospitalization still increased with decreasing gestational age (10.2% vs 4.3% for infants < or =26 weeks' gestation vs those 30-32 weeks' gestation). Analysis indicated that both forms of RSV prophylaxis would increase the net cost of care for all groups. Palivizumab was more cost-effective than RSV-Ig for preventing RSV hospitalization among infants who required respiratory support at less than 36 weeks of PCA, especially those born at 26 weeks' gestation or earlier. Overall, RSV-Ig was more cost-effective than palivizumab for infants requiring respiratory support at 36 weeks of PCA or older. CONCLUSIONS: This analysis suggests that available forms of RSV prophylaxis would increase the net cost of care not only for the entire cohort but for each of the subgroups studied. However, the RSV hospitalization rate and the cost-effectiveness of prophylaxis varied markedly by subgroup.

Antibodies, Monoclonal↗
PubMed1999

Lipid intolerance in neonates receiving dexamethasone for bronchopulmonary dysplasia.

BACKGROUND: We hypothesized that dexamethasone induces hypertriglyceridemia (triglyceride levels >2.82 mmol/L [250 mg/dL]) and increases free fatty acid (FFA) levels and that steroid-induced hypertriglyceridemia is associated with hyperinsulinemia and elevated FFA levels. OBJECTIVE: To study the effect of dexamethasone sodium phosphate on lipid metabolism in neonates receiving intravenous lipids. DESIGN: A prospective cohort study with patients serving as their own controls. SETTING: Neonatal Intensive Care Unit, Children's Hospital at Strong, Rochester, NY. METHODS: All neonates younger than 29 weeks' gestational age at birth receiving 3 g/kg per day of intravenous lipids who were to start dexamethasone therapy for bronchopulmonary dysplasia were eligible. Exclusion criteria included neonates with active infection, prior hypertriglyceridemia, bleeding manifestations, recent surgery, thyroid medication, and human recombinant insulin intravenous infusion therapy. Ten neonates were studied. Blood was drawn for triglyceride, FFA, and insulin assays before initiating and at 1, 2, 3, and 5 days after starting dexamethasone therapy. On day 3, dexamethasone dosage was decreased as per protocol. Intravenous lipid intake was kept constant. Statistical analysis was done using a paired t test. RESULTS: Six of 10 neonates reached a state of hypertriglyceridemia (95% confidence interval, 26.2%-87.8%). The mean average increase in triglycerides, insulin, and FFA levels in neonates receiving 3 g/kg per day of intravenous lipids after initiation of dexamethasone therapy was 0.75 mmol/L (66.6 mg/dL) (P=.007), 127 pmol/L (P = .006), and 47.5 micromol/L (P = .65), respectively. Six neonates who developed hypertriglyceridemia had significantly elevated mean peak FFA levels (918.3 micromol/L) prior to developing hypertriglyceridemia compared with 4 neonates (mean peak FFA levels, 380.2 micromol/L) who had triglyceride levels lower than 2.82 mmol/L (250 mg/dL) (P = .002). CONCLUSION: We conclude that dexamethasone induces hypertriglyceridemia in the presence of hyperinsulinemia and increased FFA levels.

Bronchopulmonary Dysplasia↗
PubMed1999

Disseminated coagulopathy associated with transtorcular embolization of vein of Galen aneurysm in a neonate.

We describe in this report the development of disseminated intravascular coagulopathy in a neonate after transtorcular embolization of an unusual vein of Galen aneurysm. This rare but potentially fatal complication associated with transtorcular embolization should be considered in decision-making and prognostic evaluation processes, especially in neonates with severe heart failure.

Cerebral Angiography↗
PubMed1999

Vascular endothelial growth factor in pulmonary lavage fluid from premature infants: effects of age and postnatal dexamethasone.

Corticosteroids are used to ameliorate bronchopulmonary dysplasia (BPD). They also affect normal development, including the expression of growth factors such as vascular endothelial growth factor (VEGF). Deep pulmonary lavage specimens were collected on days 1, 3, 7 and 28 of life in 40 infants of <34 weeks of gestation at birth during a randomized controlled trial of two doses of dexamethasone (DEX) at 12 and 24 h of age for BPD prophylaxis. VEGF was measured by enzyme-linked immunosorbent assay. The 18 DEX and 21 control subjects had similar gestations, birth weights and oxygen requirements at study entry. Lavage VEGF tripled between day 1 and 3 in both groups. The day 7 levels were higher in DEX subjects than in controls. DEX and control values were similar on day 28. Higher lavage VEGF levels on days 1 and 3 were also correlated with lower gestational age at birth. Lavage VEGF levels were not associated with the development of BPD. We speculate that these DEX- and age-associated changes in VEGF may affect pulmonary angiogenesis.

Age Factors↗
PubMed1998

Cell-specific expression of fibronectin and EIIIA and EIIIB splice variants after oxygen injury.

Cellular fibronectin (cFN) expression is characteristic of injured tissues. Unlike plasma FN, cFN mRNA often contains the EIIIA or EIIIB domains. We examined the lung cell-specific expression of total cFN mRNA and the EIIIA and EIIIB splice variants in rabbits after acute oxygen injury. By in situ hybridization, control lung had low cFN mRNA. After exposure to > 95% oxygen, mRNAs for total cFN and EIIIA were noted primarily in alveolar macrophages and large-vessel endothelial cells. By 3-5 days recovery, cFN and EIIIA mRNA abundance was increased in alveolar septal cells (i.e., alveolar epithelial, interstitial, or endothelial cells) and in some large-vessel endothelial cells but was low in bronchial epithelial cells. During recovery, EIIIB mRNA was low in alveolar septal cells but was noted mainly in chondrocytes. Immunostaining for EIIIA increased during recovery, paralleling the in situ hybridizations. Because FN may modulate alveolar type II cell phenotype, we investigated type II cell cFN mRNA expression in vivo. During recovery, neither isolated type II cells nor cells with surfactant protein C mRNA in vivo contained FN mRNA. In summary, these data suggest that cFN with the EIIIA domain has a role in alveolar cell recovery from oxygen injury and that type II cells do not express cFN during recovery.

Animals↗
PubMed1998

School-age follow-up of prophylactic versus rescue surfactant trial: pulmonary, neurodevelopmental, and educational outcomes.

BACKGROUND: Exogenous surfactant replacement has improved survival and reduced pulmonary complications of prematurity. Improved early outcomes for infants of <30 weeks' gestation treated with a strategy of prophylactic versus rescue surfactant, if needed, were demonstrated in a multicenter, randomized trial conducted between 1985 and 1988. We reevaluated a subset of survivors from this trial to determine the pulmonary and neurodevelopmental outcomes at school age. METHODS: At 4.5 to 8 years of age, all survivors from one of the three centers were located, and 96% were evaluated. The original randomization included stratification by center and followed an intention-to-treat methodology in assessing the efficacy of prophylactic versus rescue treatment with surfactant. The follow-up test battery included a health-assessment questionnaire, spirometry, 88% saturation test, neurologic examination, and the McCarthy Scales of Children's Abilities (MSCA) and the Conners' Parent Rating Scale-48. Educational achievement was determined by school class placement and teachers' reports of achievement. RESULTS: Of the 192 children originally enrolled, 154 survived. Evaluations were performed on 148 of these infants. An abnormal pulmonary history was found in 45 (30%) of the children: 16 (22%) in the prophylactic group and 29 (39%) in the rescue group. Formal pulmonary function was evaluated in 81 children; 29 (78%) in the prophylactic group and 33 (75%) in the rescue group were considered abnormal. No significant differences were found between the two groups on either cognitive or motor subscales of the MSCA, the Conners' Parent Rating Scale-48, the neurologic examination, the education services received in school, or the teacher ratings of below-average academic performance. Intelligence scores measured on the MSCA were low-normal for both groups. Some level of educational assistance was being provided to 72 (49%) of the cohort studied, and both groups had below average educational performance and increased needs for educational assistance. CONCLUSIONS: Prophylactic surfactant administration to infants of <30 weeks' gestation was associated with fewer long-term clinical pulmonary complications than assignment to rescue administration. Formal pulmonary testing at school age did not reveal significant differences between treatment groups in those infants who could be tested. There also were no group differences found on neurologic, cognitive, behavioral, or educational assessments at school age.

Child↗
PubMed1998

Comparison of two strategies for surfactant prophylaxis in very premature infants: a multicenter randomized trial.

INTRODUCTION: Previous trials of surfactant therapy in premature infants have demonstrated a survival advantage associated with prophylactic therapy as an immediate bolus, compared with the rescue treatment of established respiratory distress syndrome. The optimal strategy for prophylactic therapy, however, remains controversial. When administered as an endotracheal bolus immediately after delivery, surfactant mixes with the absorbing fetal lung fluid and may reach the alveoli before the onset of lung injury. This approach, however, causes a brief delay in the initiation of standard neonatal resuscitation, including positive pressure ventilation, and is associated with a risk for surfactant delivery into the right main stem bronchus or esophagus. As an alternative approach, surfactant prophylaxis may be administered in small aliquots soon after resuscitation and confirmation of endotracheal tube position. Although this strategy has substantial logistical advantages in clinical practice, its efficacy has not been established. OBJECTIVE: The purpose of this study was to determine whether the established benefits of the immediate bolus strategy for surfactant prophylaxis could still be achieved using a postventilatory aliquot strategy after initial standard resuscitation and stabilization. DESIGN: Multicenter randomized clinical trial with patients randomized before delivery to immediate bolus or postventilatory aliquot therapy. PARTICIPANTS: Inborn premature infants delivered to mothers at an estimated gestational age of 24[0/7] to 28[6/7] weeks. INTERVENTIONS: Those infants who were randomized to the immediate bolus strategy were intubated as rapidly as possible after birth, and a 3-mL intratracheal bolus of calf lung surfactant extract (Infasurf) was administered before the initiation of positive pressure ventilation. Those infants who were randomized to the postventilatory aliquot strategy received standard resuscitation measures with intubation by 5 minutes of age, if not required earlier. At 10 minutes after birth, 3 mL of surfactant was administered in 4 divided aliquots of 0.75 mL each. Patients in both groups were eligible to receive up to three additional doses of surfactant as rescue therapy in the neonatal intensive care unit, if needed. OUTCOME MEASURES: The primary outcome variable was survival to discharge to home. Secondary variables included neonatal complications and requirement for oxygen therapy at 36 weeks' postmenstrual age. RESULTS: Among three centers, 651 infants were enrolled and randomized before delivery. Survival to discharge to home was similar for the two strategies for surfactant therapy as prophylaxis: 76% for the immediate bolus group and 80% for the postventilatory aliquot group. In a secondary analysis, the rate of supplemental oxygen administration at 36 weeks' postmenstrual age was 18% for the immediate bolus group and 13% for the postventilatory aliquot group. CONCLUSIONS: Survival to discharge to home was similar with immediate bolus and postventilatory aliquot strategies for surfactant prophylaxis. Because of its logistical advantages in the delivery room and its beneficial effects on prolonged oxygen requirements, we recommend the postventilatory aliquot strategy for surfactant prophylaxis of premature infants delivered before 29 weeks' gestation.

Drug Administration Schedule↗
PubMed1996

Differential cytokine mRNA expression by neonatal pulmonary cells.

The purpose of this study was to describe cytokine profiles of human neonatal pulmonary cells isolated by tracheal aspiration (TA) and by deep pulmonary lavage (DPL). We hypothesized that mRNA phenotyping, using the technique of reverse transcriptase polymerase chain reaction (RT-PCR), would reveal differences in cytokine expression patterns between cells from proximal and distal airway compartments. We reasoned that cells derived by DPL may reflect pathogenic pathways indicative for the development of bronchopulmonary dysplasia in the premature infant. Here we have described the detection of mRNA for IL-1 alpha, IL-1 beta, IL-6, IL-8, and tumor necrosis factor-alpha. Fourteen paired TA and DPL samples from six premature infants were collected at 1, 7, or 28 d of age. Two of 14 samples were negative for beta-actin (a ubiquitous mRNA) by RT-PCR and were excluded from further analysis. Each of the remaining 12 samples expressed IL-8. Furthermore, each cytokine could be expressed by TA or DPL cells. Cytokine mRNA phenotype profiles were found to differ between TA and DPL cells in four of five paired samples. Our results show that cells retrieved from these two pulmonary compartments are sources for these cytokines and suggest that RT-PCR of TA/DPL cells can be used to test hypothetical predictive markers for the development of bronchopulmonary dysplasia.

Bronchoalveolar Lavage Fluid↗
PubMed1995

Interleukin-8 and monocyte chemoattractant protein-1 mRNAs in oxygen-injured rabbit lung.

The chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) are neutrophil and monocyte attractants, respectively. We hypothesized that IL-8 and MCP-1 mRNA expression in alveolar macrophages (AM) lavaged from rabbit lung would be increased by oxygen exposure, which is known to induce inflammation. Adult rabbits were exposed to > 95% oxygen for up to 64 h and allowed to recover in room air for up to 72 h before killing and pulmonary lavage. Numbers of lavageable polymorphonuclear cells (PMN) and AM rose during the exposure protocol. Quantitative in situ hybridization with 3H-labeled cRNA probes showed both IL-8 and MCP-1 mRNA expression in AM during oxygen exposure, with peak levels of IL-8 mRNA at 56-h oxygen exposure and of MCP-1 mRNA at 64-h oxygen exposure with 24-h room air recovery. IL-8 mRNA was present in PMN between 48-h oxygen exposure and 64-h oxygen exposure with 24-h room air recovery. MCP-1 mRNA was not expressed in PMN. This pattern of chemokine mRNA expression emphasizes the importance of inflammatory cells as effectors in the pulmonary response to oxygen exposure.

Animals↗
PubMed1995

Cell-specific expression of fibronectin in adult and developing rabbit lung.

Fibronectin (FN), a glycoprotein component of the extracellular matrix, plays a role in tissue morphogenesis and tissue-specific differentiation through its effects on cell adhesion, cell shape, and cytoskeletal organization. Immunohistochemistry has been used to show that during lung development FN deposition changes, yet the cell-specific sites of pulmonary FN synthesis have not been determined. Because cellular FN synthesis is reflected by FN mRNA abundance, we performed in situ hybridizations to identify pulmonary tissue with the capacity to synthesize FN. Both in situ mRNA hybridization and immunohistochemical staining were performed on tissue sections from lungs of adults and late gestation fetal and neonatal rabbits. In adults, FN transcripts and immunostaining were clearly seen in endothelial cells, smooth muscle cells, and chondrocytes. During lung development, FN transcripts were virtually ubiquitous except in airway epithelium. There was a gradual decrease in FN mRNA abundance with advancing fetal age, but low levels of FN mRNA persisted in neonatal and adult lungs. In contrast, parenchymal immunostaining increased throughout fetal development and remained elevated in the newborn. FN immunostaining was lower in adult lung. In all tissues examined, airway epithelial cells contained no FN transcripts above background. However, immunostaining was detected in airway basement membrane zones and on luminal surfaces of some epithelial cells. The lack of FN transcripts in airway epithelial cells suggests that FN synthesis does not normally occur in this cell type and that its associated FN immunostaining is from another source. The colocalization of FN mRNA and protein in pulmonary endothelial cells, smooth muscle cells, and chondrocytes in adults strongly suggests that these cells are sites of FN synthesis.

Animals↗
PubMed1994

Amnioinfusion during labor complicated by particulate meconium-stained amniotic fluid decreases neonatal morbidity.

OBJECTIVE: Our purpose was to evaluate the efficacy of prophylactic amnioinfusion in decreasing neonatal morbidity associated with labor complicated by particulate meconium-stained amniotic fluid and to assess potential complications of this procedure. STUDY DESIGN: One hundred five laboring pregnant women with particulate (moderate or thick) meconium by subjective clinical analysis were randomly assigned to receive amnioinfusion or to receive standard obstetric care without amnioinfusion. Patients with any antepartum complications, other than the presence of meconium, were excluded from the study. Statistical analyses consisted of the two-tailed and paired Student t tests, Pearson chi 2 test, and Wilcoxon nonparametric test. Significance was set at p < 0.05. RESULTS: The study included 47 patients in the study group and 58 patients in the control group. A significantly greater proportion of study patients demonstrated decreased meconium concentration between rupture of membranes and delivery (46 of 46 vs 15 of 58, p < 0.001). The relative dilution of meconium consistency by objective analysis was significantly different between the study group and the control group (77.1% decrease vs 9.3% increase, p < 0.001). The proportion of neonates with meconium below the vocal cords was reduced in the study group (two of 47 vs 36 of 58, p < 0.001). Umbilical artery pH was increased in the study group neonates (7.29 +/- 0.01 vs 7.25 +/- 0.009, p < 0.05). The rate of neonatal acidemia was reduced in the study group (4 of 45 vs 12 of 50, p < 0.05). The rate of meconium aspiration syndrome was reduced in the study group (1 of 47 vs 8 of 58, p < 0.05). Maternal and neonatal morbidity rates were similar. CONCLUSION: Prophylactic amnioinfusion should be considered a possible addition to the intrapartum management of patients with particulate meconium-stained amniotic fluid.

Acidosis↗
PubMed1994

Prevention of central venous catheter-related coagulase-negative staphylococcal sepsis in neonates.

A randomized, double-blind, controlled trial was conducted to determine whether vancomycin added to parenteral alimentation solution given via a central venous catheter would decrease the incidence of catheter-related coagulase-negative staphylococcal sepsis. Seventy infants with a central venous catheter (CVC) in place were randomly selected to receive total parenteral nutrition--either the standard solution or a solution containing 25 micrograms of vancomycin per milliliter. Catheter-related sepsis was defined as the isolation of the same bacterial species from specimens of both peripheral and CVC blood with the concentration of bacteria at least tenfold greater in the specimen obtained from the CVC. Specimens from the CVCs were cultured on removal of the catheters to determine colonization. The colonization of catheters by coagulase-negative staphylococci was reduced from 40% to 22% (p = 0.03) in the vancomycin group; catheter-related sepsis was reduced from 15% to no cases (p = 0.004). Fewer infants required CVC reinsertion in the vancomycin-treated group (p = 0.02), who also regained birth weight earlier (13.4 vs 17.1 days (p = 0.014)). Adverse effects of vancomycin infusion were not observed. We conclude that vancomycin added to the solution used for total parenteral nutrition effectively reduces catheter-related sepsis in the neonatal intensive care unit and offers other potential benefits such as the need for fewer catheters and earlier weight gain. However, we do not recommend widespread implementation of this technique until there are data regarding the emergence of vancomycin-resistant organisms.

Bacteremia↗
PubMed1994

Marked twin-twin transfusion in the absence of nonimmune hydrops.

The precise pathophysiology of development of nonimmune hydrops in either the recipient or donor twin associated with twin-twin transfusion syndrome is not entirely clear. At times the recipient twin may develop nonimmune hydrops, but at other times the donor twin, and infrequently both, may develop this ominous complication. We present an unusual cases of this syndrome in which discordant twins, despite neonatal hematocrit levels of 86 and 21% were both nonhydropic and discuss the possible underlying pathophysiology of this occurrence.

Adult↗
PubMed1994

Transforming growth factor-beta 1 modulates type II cell fibronectin and surfactant protein C expression.

Extracellular matrix (ECM) deposition by alveolar type II cells is important for repair of a damaged alveolar epithelium. Transforming growth factor-beta (TGF-beta) is abundant in injured lung and has profound effects on ECM production and cell differentiation. We determined the effects of TGF-beta 1 on type II cell expression of fibronectin and surfactant protein C (SP-C) in vitro. TGF-beta 1 increased the proportion of type II cells with detectable mRNA for fibronectin from 9 to 68%, as demonstrated by in situ hybridization, and increased the fibronectin mRNA levels 10-fold. TGF-beta 1-treated cultures had increased immunostaining for fibronectin and increased secretion of metabolically labeled fibronectin. A decreased proportion of type II cells treated with TGF-beta 1 had detectable mRNA for SP-C, and the abundance of this message per cell decreased to 25% of control values. No effects of TGF-beta 1 were noted on the proportion of cells that contained lamellar bodies, which was 87% in both groups. These data indicate that TGF-beta 1 regulates type II cell fibronectin protein an mRNA levels. In addition, the decreased abundance of SP-C mRNA suggests that TGF-beta 1 may also modulate type II cell differentiation in lung injury.

Animals↗