Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fetuses of streptozotocin-induced diabetic rats exhibited delayed lung maturation and a 40% reduction in the steady-state level of lung Na+,K(+)-ATPase alpha 1 subunit mRNA and Na+,K(+)-ATPase activity at 21 d of gestation. In in situ hybridization experiments the signal specific for Na(+)-pump alpha 1 subunit message was strongest above columnar epithelial cells of air-conducting structures. Strong labeling was also present above cuboidal cells lining the forming alveoli, but not above mesenchymal cells. Immunocytochemical localization of the protein paralleled the distribution of the mRNA. Mesenchymal cells were more abundant in fetal lungs of diabetic mothers, and thus the decreased overall levels of Na+,K(+)-ATPase may result from the observed morphological pulmonary immaturity. One day after birth there was no apparent difference in lung morphology at the light microscopic level, in the localization or the steady-state level of Na+,K(+)-ATPase alpha 1 isoform mRNA, or in enzyme activity. Na+,K(+)-ATPase has a likely role in the active phase of fluid absorption in the airways of newborns before the onset of breathing. Decreased fluid clearance and lack of thinning of the lung's connective tissue may contribute to the increased risk for respiratory distress in infants of diabetic mothers.
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PMID:Effects of maternal diabetes on fetal rat lung ion transport. Contribution of alveolar and bronchiolar epithelial cells to Na+,K(+)-ATPase expression. 184 38

Severe respiratory distress developed in a 5-month-old infant approximately ten days after pneumonectomy for complete sequestration of the right lung. Right pneumonectomy syndrome was diagnosed by bronchography, which revealed thinning and obstruction of the left main bronchus during expiration. A right thoracotomy was then performed, and an inflatable tissue expander with a subcutaneous injection port was inserted into the right chest cavity to prevent recurrence of the mediastinal shift and to allow for future growth. The patient has done well, requiring reinjection of the prosthesis with additional volume on one occasion in a 20-month period of follow-up.
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PMID:Right pneumonectomy syndrome in infancy treated with an expandable prosthesis. 236 14

Trypanosoma cruzi was believed responsible for causing chronic dilatative myocarditis in 2 female hunting dogs. Clinical signs included ascites, respiratory distress, thoracic effusion, cyanosis, and weak pulse with ventricular arrhythmias. Electrocardiography indicated first-degree heart block, chamber enlargement, and ventricular-based arrhythmias unresponsive to treatment. M-mode echocardiography of 1 dog confirmed bilateral cardiac enlargement and septal and left ventricular free wall thinning. Multifocal infiltrates of plasma cells, lymphocytes, and histiocytes, cardiocyte degeneration, and multifocal fibrosis were the predominant histologic lesions. Trypanosoma cruzi pseudocysts were infrequently found.
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PMID:Chronic dilatative myocarditis caused by Trypanosoma cruzi in two dogs. 258 22

Review of published reports shows confusion regarding the pathologic sequelae of neonatal respiratory distress. To examine this problem the authors studied histologic slides of lung from 46 patients so diagnosed listed in the autopsy files of The Johns Hopkins Hospital. Two distinct morphologic patterns emerged. In 26 patients (Group 1) there were varying sized areas of interstitial fibrosis with associated distortion of air spaces. The process was nonspecific and closely resembled the interstitial fibrosis of varying etiologies found in adults. This lesion appears to correspond to most descriptions of bronchopulmonary dysplasia. A second process predominated in 10 patients (Group 3). There were normal conducting bronchi, marked uniform enlargement of distal air spaces, and little or no interstitial fibrosis. In 10 patients (Group 2) both lesions coexisted. To gain further insight into the morphology of these disorders, the authors reconstructed serial histologic sections of lung from three infants of varying sizes with normal lungs and infants of varying ages with bronchopulmonary dysplasia. The results confirmed the observations made on routine histologic sections by showing interstitial fibrosis in the early stages of bronchopulmonary dysplasia and a reduced number of very large terminal air spaces without interstitial fibrosis in the late stages. There were no obvious differences in the clinical courses of infants with the different morphologic stages; but Group 1 patients averaged 39 days of age, Group 2 lived 142 days, and Group 3 survived 277 days. It seems probable that early bronchopulmonary dysplasia is simply the healing of alveolar wall injury of whatever cause, most commonly hyaline membrane disease of the newborn; and that in the later phases of repair, with continuing growth, there is a thinning of airway walls, but a failure of alveolar development. Recognition of these two pathologically different patterns is important for further studies of the pathogenesis of bronchopulmonary dysplasia.
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PMID:The progression of morphologic changes in bronchopulmonary dysplasia. 364 32

Neonates with congenital diaphragmatic hernia (CDH) experience a high mortality despite intensive medical and surgical management. The associated pulmonary hypoplasia is accompanied by an underlying biochemical deficiency that bears similarity to respiratory distress syndrome (RDS) in the premature newborn. Using therapies extrapolated from those used to treat RDS, the authors have previously shown correction of the immature pulmonary biochemical indices in the nitrofen rat CDH model. This study investigates the functional and histological outcome of prenatal hormone therapy on CDH rats. Compared with saline-treated CDH controls, dexamethasone-treated CDH animals achieved significant increases in lung distensibility (P = .0006) and functional residual capacity (P = .004); CDH rats treated with combined dexamethasone and thyrotropin-releasing hormone (TRH) showed improved functional residual capacity (P = .043) and alveolar stability (P = .025); CDH animals treated with TRH alone (TRH-CDH) showed no improvement in any parameter tested. Histologically, the lungs from dexamethasone- and dexamethasone-TRH-treated CDH animals showed changes that included narrow septal walls, increased air saccule size, and thinning of the pulmonary interstitium compared with the lungs of saline or TRH-CDH rats, which were developmentally arrested at the canalicular stage. Lung weights and lung weight-body weights ratios were similar in all CDH rats, confirming that treatment did not impair pulmonary growth. These results support the potential clinical use of prenatal pharmacological therapies to treat human fetuses with prenatally diagnosed CDH.
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PMID:Prenatal hormonal therapy improves pulmonary compliance in the nitrofen-induced CDH rat model. 870 26

Glucocorticoids are widely used in perinatology, since they decrease the incidence of respiratory distress syndrome and chronic lung disease. However, evidence is now increasing that their use in this age group may result in impaired alveolar lung growth and general development. The aim of this study was to determine whether a low dose of hydrocortisone (1 mg/kg/day for 11 days) was deleterious to lung growth in rat pups, as compared to an equivalent dose of dexamethasone. While both dexamethasone and hydrocortisone increased alveolar diameter with thinning of the interairspace walls, only dexamethasone reduced the overall internal surface area of the lung available for respiratory exchange. Changes were more marked with dexamethasone as compared to hydrocortisone, which did not appear to affect alveolar septation. In conclusion, a prolonged course of low-dose hydrocortisone may be deleterious for alveolar lung growth in rat pups, but the changes are less marked than those caused by dexamethasone.
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PMID:Differential effect of dexamethasone and hydrocortisone on alveolar growth in rat pups. 1200 Dec 77

Glucocorticoids are given antenatally to promote pulmonary epithelial maturation and prevent respiratory distress syndrome in premature newborns. In contrast to airway changes, effects on vessels are less documented. We hypothesized that antenatal betamethasone (BM) administration promotes vascular development. Does received either a course of BM = 0.05 mg/kg/day (18 does, 70 fetuses), BM = 0.1 mg/kg/day (20 does, 75 fetuses), or saline (11 does, 92 fetuses) starting on d25, 26 (canalicular stage), d27, d28 (saccular stage), and d29 (alveolar stage) of gestation. In total 236 fetuses from 49 does were examined at term (d31) in terms of vascular development. Lung specimens were weighed and formalin fixed for morphometry. We determined differences in fetal body, liver and lung weight, proportionate medial thickness, muscularization of intra-acinar vessels, number of vessels under 100 microm, as well as immunoreactivity to Flk-1 in vascular smooth muscle and endothelial cells. A dose-dependent reduction in neonatal body and organ weight was observed in fetuses exposed to BM at d25. In contrast, term liver weight increased after late administration of BM (d28, 29). There was a dose- and time-dependent thinning of the pulmonary arterial media, which coincided with a decreased proportion of intra- and pre-acinar muscularized arteries (ED <or= 60 microm) and increased microvascularization (ED <or= 30), as well as increased endothelial immunoreactivity for Flk-1. Analyzing our data using a purpose designed geometrical model, the results suggest that maternal administration of BM promotes changes in vascular morphology, which may be compatible with remodeling and vessel formation.
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PMID:Effects of betamethasone on peripheral arterial development in term fetal rabbit. 1861 70

Elevated levels of organochlorines (OC) have been reported in Inuit populations in the Arctic. We hypothesized that prenatal exposure to a Canadian Arctic OC mixture adversely affects male reproductive function and health with age. Sprague-Dawley female rats (F0) were gavaged with an environmentally relevant concentration of an Arctic OC mixture or corn oil (Control) during mating with untreated males until parturition (F1 litters). After postnatal day (PND) 90, the weights of the OC F1 males differed dramatically relative to Controls (P<0.05; n=10) and they exhibited respiratory distress. Except for possible thinning of the alveolar barrier, histological observation of the lungs revealed no apparent pathology to explain the respiratory distress. At PND 365, OC F1 males had reduced relative reproductive organ weights and lower sperm quality than Controls (P<0.05). At PND 90, OC F1 males were subfertile (P<0.05), but were infertile at PND 365. In conclusion, environmentally relevant prenatal OC exposure reduced reproductive function and health in aging male rats, providing new insight into the effects of early-life exposures to these contaminants.
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PMID:Prenatal exposure to an environmentally relevant mixture of Canadian Arctic contaminants decreases male reproductive function in an aging rat model. 3010 27

Bronchopulmonary dysplasia (BPD) remains a major respiratory illness in extremely premature infants. The biological mechanisms leading to BPD are not fully understood, although an arrest in lung development has been implicated. The current study aimed to investigate the occurrence of autophagy in the developing mouse lung and its regulatory role in airway branching and terminal sacculi formation. We found 2 windows of epithelial autophagy activation in the developing mouse lung, both resulting from AMPK activation. Inhibition of AMPK-mediated autophagy led to reduced lung branching in vitro. Conditional deletion of beclin 1 (Becn1) in mouse lung epithelial cells (Becn1Epi-KO), either at early (E10.5) or late (E16.5) gestation, resulted in lethal respiratory distress at birth or shortly after. E10.5 Becn1Epi-KO lungs displayed reduced airway branching and sacculi formation accompanied by impaired vascularization, excessive epithelial cell death, reduced mesenchymal thinning of the interstitial walls, and delayed epithelial maturation. E16.5 Becn1Epi-KO lungs had reduced terminal air sac formation and vascularization and delayed distal epithelial differentiation, a pathology similar to that seen in infants with BPD. Taken together, our findings demonstrate that intrinsic autophagy is an important regulator of lung development and morphogenesis and may contribute to the BPD phenotype when impaired.
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PMID:Autophagy is required for lung development and morphogenesis. 3116 36