Pulmonary function was assessed in newborn wild-type and homozygous and heterozygous surfactant protein B (SP-B)-deficient mice after birth. SP-B+/+ and SP-B+/− mice became well oxygenated and survived postnatally. Although lung compliance was decreased slightly in the SP-B+/− mice, lung volumes and compliances were decreased markedly in homozygous SP-B−/− mice. They died rapidly after birth, failing to inflate their lungs or oxygenate. SP-B proprotein was absent in the SP-B−/− mice and was reduced in the SP-B+/− mice, as assessed by Western analysis. Surfactant protein A, surfactant proprotein C, surfactant protein D, and surfactant phospholipid content in lungs from SP-B+/− and SP-B−/− mice were not altered. Lung saturated phosphatidylcholine and precursor incorporation into saturated phosphatidylcholine were not influenced by SP-B genotype. Intratracheal administration of perfluorocarbon resulted in lung expansion, oxygenation, and prolonged survival of SP-B−/− mice and in reduced lung compliance in SP-B+/+ and SP-B+/− mice. Lack of SP-B caused respiratory failure at birth, and decreased SP-B protein was associated with reduced lung compliance. These findings demonstrate the critical role of SP-B in perinatal adaptation to air breathing.

Surfactant protein-B (SP-B) is a small, hydrophobic peptide that plays a critical role in pulmonary function and surfactant homeostasis. To determine whether SP-B protects mice from oxygen-induced injury, heterozygous SP-B(+/-) gene-targeted mice and wild-type SP-B(+/+) littermates were exposed to hyperoxia (95% oxygen for 3 d) or room air. Although specific lung compliance in room air in SP-B(+/-) mice was slightly reduced as compared with that in SP-B(+/+) mice, it was reduced more markedly during hyperoxia (46% versus 25% decrease, respectively). The larger decrease in lung compliance in SP-B(+/-) mice was associated with increased severity of pulmonary edema, hemorrhage and inflammation, lung permeability and protein leakage into the alveolar space. Hyperoxia increased SP-B messenger RNA (mRNA) and total protein concentrations by 2-fold in SP-B(+/+) and SP-B(+/-) mice, but decreased the abundance of SP-B protein in lavage fluid relative to total protein only in SP-B(+/-) mice. Hyperoxia increased SP-B expression, but apparently not enough to maintain SP-B function and lung compliance in the presence of increased protein leakage in SP-B(+/-) mice. Increased alveolar-capillary leakage and relative deficiency of SP-B may therefore contribute to oxygen-induced pulmonary dysfunction in SP-B(+/-) mice. These data support the concept that SP-B plays an important protective role in the lung.

Delayed lung maturation and lower levels of surfactant phosphatidylcholine have been previously identified in male fetuses compared with female fetuses in several species. We investigated the mechanisms for sex differences in surfactant content by examining parameters of phosphatidylcholine turnover and biosynthesis; the latter was evaluated by measuring metabolic steps within the biosynthetic pathway. Compared with male lung cells, freshly isolated lung cells from female fetuses contained higher levels of disaturated phosphatidylcholine, a marker of surfactant lipid. Female mixed monolayer cultures exhibited a 71% increase in choline incorporation into disaturated phosphatidylcholine compared with male cultures. Male cultures exhibited significantly greater release of [3H]-arachidonic acid into the medium compared with females, suggesting sex differences in phospholipase activity. However, pulse-chase studies showed no sex differences in degradation of disaturated phosphatidylcholine, which was confirmed by assays of phospholipase A2, phosphatidylcholine-specific phospholipase C, and phospholipase D. Female mixed lung cells, however, had greater rates of cellular choline transport and activity of cytidylyltransferase, the rate-regulatory enzyme for phosphatidylcholine synthesis. Separate studies showed that exposure of sex-specific pretype II cell cultures to cortisol-stimulated fibroblast-conditioned medium plus transforming growth factor-beta-neutralizing antibody stimulated cytidylyltransferase activity to a greater extent in male cells compared with female cells. These studies indicate that sex differences in surfactant phospholipid content are not due to differences in phospholipid turnover, but rather differential regulation of specific metabolic steps within the surfactant biosynthetic pathway. The data also support a role for transforming growth factor-beta as a negative regulator of a key surfactant biosynthetic enzyme within male lungs.

Bacillus cereus (B. cereus) meningitis sometimes occurs in patients with risk factors, which are associated with central nervous system (CNS) anomalies, surgical or anaesthetic access to CNS. We observed two cases of B. cereus meningitis in neonates without such risk factors. The clinical courses of both neonates were fulminant, and routine antibiotic therapy failed. Intracranial haemorrhage was evident at autopsy. According to the previous neonatal case reports and our experience, we found that six of seven neonates were premature babies admitted to the neonatal intensive care unit, five died within a week of onset of the disease, and six had intracranial haemorrhage. We speculate that B. cereus meningitis may occur in neonates, even without any of the risk factors previously described in adult case reports, and that the clinical manifestations of the meningitis might be characterized by the high incidence of intracranial haemorrhage and poor mortality.

Ultrasonography is used for the prenatal diagnosis of hypoplastic lungs. However, ultrasound poses problems because of difficulties in getting the entire lung in perspective and the results depend on the skill of the examiner. When the alveolar formation of the fetal lung is retarded, the fetus is predicted to show an altered density on MRI using an SSFSE sequence due to a varied amount of alveolar lung fluid. We present a case of twins who showed a marked difference in signal intensity of the lung on MRI, which was useful for predicting the fetal pathophysiology. Intrauterine MRI provides the possibility of diagnosing hypoplastic lungs prenatally.