摘要:

Obstruction of the fetal trachea is a potent stimulus for fetal lung growth and may have therapeutic potential in human fetuses with lung hypoplasia. However, the effects of increased lung expansion on lung development near midgestation, which is the preferred timing for fetal intervention, have not been well studied. Our aim was to determine the effects of increased lung expansion on lung development at 75–90 d of gestation in fetal sheep. In three groups of fetuses (n= 4 for each), the trachea was occluded for either 10 [10-d tracheal occlusion (TO) group] or 15 d (15-d TO group) or left intact (control fetuses). TO for both 10 and 15 d caused fetal hydrops, resulting in significantly increased fetal body weights. Both periods of TO significantly increased total lung DNA contents from 99.8 ± 10.1 to 246.0 ± 5.3 and 246.9 ± 48.7 mg in 10- and 15-d TO fetuses, respectively. TO for 10 and 15 d also increased airspace diameter, although the percentage of lung occupied by airspace was not increased in 10-d TO fetuses due to large increases in interairway distances; this resulted from a large increase in mesenchymal tissue. The interairway distances at 15 d of TO were reduced compared with the 10-d value but were still ∼30% larger than control values. We conclude that TO at <90 d of gestation in fetal sheep induces a greater increase in lung tissue growth than later in gestation but also causes fetal hydrops and produces changes in lung structure that are not compatible with efficient gas exchange. Thus, increased lung expansion at a similar stage of development in human fetuses is unlikely to induce changes in lung development that would facilitate gas exchange after birth.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We hypothesized that the inter-breath variability of the breathing pattern in newborn rats varied with temperature and oxygenation. Breathing pattern was recorded in 4-day-old rats by airflow plethysmography, during normoxia in warm (control) and cold conditions, or during hypoxia (inspired O2= 10%) in warm or cold conditions, each lasting 15 min. The warm phase (36°C) either preceded or followed the cold (24°C). Time-domain analysis was applied to 500 continuous breaths recorded toward the end of each phase. All parameters describing the breathing pattern (instantaneous ventilation, tidal volume, and inspiratory and expiratory time) had lower variability when the condition differed from controli.e.in cold or hypoxia, with no correlation with the absolute level of ventilation. The difference in variability between warm-normoxia and the other conditions was reduced when cold preceded the warm phase. Gaseous metabolism was increased in cold because of thermogenesis. When the cold preceded the warm phase the increased thermogenesis partly persisted into the warm phase, raising the metabolic level. We conclude that the variability of the breathing pattern in newborn rats1) does not depend on the absolute level of ventilation, and2) is reduced by the increased chemical stimuli occurring during cold-hypermetabolism or hypoxia. In normoxia in warm condition metabolic and chemical stimuli are low, and the variability is the highest. The results are in agreement with the clinical observations of a higher incidence of apneic episodes in infants during warm conditions.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Viral respiratory infections cause acute bronchiolitis and physiologic dysfunction in human infants and in animals. It is possible that the pulmonary dysfunction is a consequence of the inflammatory cells that are recruited during viral illness. We hypothesized that blockade of intercellular adhesion molecule-1 (ICAM-1), a major cell adhesion molecule, would impede the ingress of leukocytes during viral infection and attenuate virus-induced pulmonary dysfunction. Adult male rats were inoculated with parainfluenza type 1 (Sendai) virus or sterile vehicle, and treated with blocking or nonblocking MAb specific for rat ICAM-1. Respiratory system resistance, oxygenation (Pao2), methacholine responsiveness, and bronchoalveolar lavage (BAL) leukocyte counts were measured in anesthetized, paralyzed, ventilated rats. Treatment with the blocking ICAM-1 antibody reduced virus-induced increases in BAL neutrophils and lymphocytes by 70% (p< 0.001), but did not affect BAL monocytes/macrophages. Peripheral blood leukocyte counts were elevated in anti-ICAM-1 blocking antibody-treated rats (p= 0.0003). Although virus-induced increases in resistance and decreases in Pao2were not affected by anti-ICAM-1 treatment, there was a small but significant attenuation of virus-induced methacholine hyperresponsiveness (p= 0.02). We conclude that ICAM-1 has an important role in neutrophil and lymphocyte infiltration during respiratory viral illness, and that virus-induced changes in pulmonary physiology are not related directly to the numbers of neutrophils and lymphocytes that migrate to the air spaces during infection.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We measured cell surface expression of CD34, HLA-DR, CD38, CD19, CD33, CD71, and CD45 antigens in the hematopoietic progenitor cells of fetal cord blood to investigate immunophenotypic changes at different gestational ages. These antigens were identified by flow cytometry in 11 fetuses (gestational age 19–24 wk, in 12 preterm (25–28 wk) and in ten newborn infants born at term. The frequency and number of CD34+cells were higher in the blood of the 11 fetuses; in addition, a statistically significant inverse correlation between number of CD34+cells and advancing gestational age was noted. The numbers of CD34+CD19+, CD34+CD33+, and CD34+CD45+coexpressing cells were significantly higher in the fetuses, whereas CD34+CD38+cells were more represented in the neonates at term. Gestational age was inversely correlated with the number of CD34+CD19+and CD34+CD33+coexpressing cells. A positive correlation between gestational age and CD34+CD38+cells was noted. The number of CD34–CD19+, CD34–CD38+, and CD34–CD45+cells was higher in term infants; furthermore, a significant correlation between advancing gestational age and CD34–CD38+or CD34–CD45+cells was demonstrated. The proliferative capacity was also higher at lower gestational ages. These data suggest that the development and lineage commitment of fetal cord blood hematopoietic progenitor cells are very active during the last two trimesters of pregnancy. The most significant changes of hematopoietic cells maturation seem to occur within 25 wk of gestation.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

An 4-mo-old male was found to have an isolated increase in 2-methylbutyrylglycine (2-MBG) and 2-methylbutyrylcarnitine (2-MBC) in physiologic fluids.In vitrooxidation studies in cultured fibroblasts using13C- and14C-labeled branched chain amino acids indicated an isolated block in 2-methylbutyryl-CoA dehydrogenase (2-MBCDase). Western blotting revealed absence of 2-MBCDase protein in fibroblast extracts; DNA sequencing identified a single 778 C>T substitution in the 2-MBCDase coding region (778 C>T), substituting phenylalanine for leucine at amino acid 222 (L222F) and absence of enzyme activity for the 2-MBCDase protein expressed inEscherichia coli. Prenatal diagnosis in a subsequent pregnancy suggested an affected female fetus, supporting an autosomal recessive mode of inheritance. These data confirm the first documented case of isolated 2-MBCDase deficiency in humans.

ISSN:0031-3998    

出版商:OVID    

年代:2000

数据来源: OVID