Mechanical stretch promotes alveolar epithelial type II cell differentiation.

Functional maturation of pulmonary alveolar epithelial cells is crucial for extrauterine survival. Mechanical distension and mesenchymal-epithelial interactions play important roles in this process. We hypothesized that mechanical stretch simulating fetal breathing movements is an important regulator of pulmonary epithelial cell differentiation. Using a Flexercell Strain Unit, we analyzed effects of stretch on primary cultures of type II cells and cocultures of epithelial and mesenchymal cells isolated from fetal rat lungs during late development. Cyclic stretch of isolated type II cells increased surfactant protein (SP) C mRNA expression by 150 +/- 30% over controls (P < 0.02) on gestational day 18 and by 130 +/- 30% on day 19 (P < 0.03). Stretch of cocultures with fibroblasts increased SP-C expression on days 18 and 19 by 170 +/- 40 and 270 +/- 40%, respectively, compared with unstretched cocultures. On day 19, stretch of isolated type II cells increased SP-B mRNA expression by 50% (P < 0.003). Unlike SP-C, addition of fibroblasts did not produce significant additional effects on SP-B mRNA levels. Under these conditions, we observed only modest increases in cellular immunoreactive SP-B, but secreted saturated phosphatidylcholine rose by 40% (P < 0.002). These results indicate that cyclic stretch promotes developmentally timed differentiation of fetal type II cells, as a direct effect on epithelial cell function and via mesenchymal-epithelial interactions. Expression of the SP-C gene appears to be highly responsive to mechanical stimulation.

Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression.

Mutations of the ribosomal protein S19 (RPS19) gene were recently identified in 10 patients with Diamond Blackfan anemia (DBA). To determine the prevalence of mutations in this gene in DBA and to begin to define the molecular basis for the observed variable clinical phenotype of this disorder, the genomic sequence of the 6 exons and the 5' untranslated region of the RPS19 gene was directly assessed in DBA index cases from 172 new families. Mutations affecting the coding sequence of RPS19 or splice sites were found in 34 cases (19.7%), whereas mutations in noncoding regions were found in 8 patients (4.6%). Mutations included nonsense, missense, splice sites, and frameshift mutations. A hot spot for missense mutations was identified between codons 52 and 62 of the RPS19 gene in a new sequence consensus motif W-[YFW]-[YF]-x-R-[AT]-A-[SA]-x-[AL]-R-[HRK]-[ILV]-Y. No correlation between the nature of mutations and the different patterns of clinical expression, including age at presentation, presence of malformations, and therapeutic outcome, could be documented. Moreover, RPS19 mutations were also found in some first-degree relatives presenting only with isolated high erythrocyte adenosine deaminase activity and/or macrocytosis. The lack of a consistent relationship between the nature of the mutations and the clinical phenotype implies that yet unidentified factors modulate the phenotypic expression of the primary genetic defect in families with RPS19 mutations.

Long-term monitoring of intracranial pressure in hydrocephalic children not affected by cerebral tumor.

Long-term epidural intracranial pressure (ICP) recordings were performed in 10 hydrocephalic children, not affected by cerebral tumor. The work concerns the identification of A and B Lundberg's waves during normal sleep in the ICP pattern. Plateau-waves of high amplitude and long duration were measured in one patient. A base-line pressure higher than normal was found in the other cases in which waves during sleep were seldom revealed. Five children were monitored by studying the pressure pattern after shunt surgery. The Authors discuss the implication of the rarity of plateau-waves in infancy and the cause of this phenomenon.

A proposal method for the assessment of cerebrospinal fluid pressure in the cerebral ventricles.

This work presents a possible method of overcoming difficulties arising during the recording of intracranial pressure (ICP) from the cerebral ventricles of patients suffering from head injuries or intracranial space occupying lesions. The main difficulties in obtaining these measurements are the risk of infection and measurement errors caused by artefacts from head movements. These two problems arise when a cannula inserted into the cerebral ventricle is connected outside the skull to an external transducer measuring pressure. We propose a method utilizing a modified flushing shunt connected to a strain gauge epidural transducer. The characteristic (voltage against pressure) of the device was tested in vitro. This calibration gave satisfactory results both in the linearity of the characteristic and in the performance of the device.