Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lung development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources
PubMed1984

The relationship between PaCO2 and ventilation parameters in predicting survival in congenital diaphragmatic hernia.

Fifty-eight infants with congenital diaphragmatic hernia presenting within the first 6 hours of life, who underwent surgical repair, were analysed prospectively in order to produce a reliable index of severity of disease that would reliably predict eventual outcome. All were treated with paralysis hyperventilation and intravenous (IV) isoproterenol for the first 48 hours. There were 30 survivors and 28 deaths in this series (mortality 48%). Using arterial PCO2 values measured 2 hours after surgical repair and correlating them with an index of mechanical ventilation (mean airway pressure and respiratory rate), we have been able to clearly define two groups of diaphragmatic hernia based on their response to IPPV. The first group, with CO2 retention and severe preductal shunting, was unresponsive to hyperventilation with high rates and pressures; the mortality was 90%. The second group responded well to hyperventilation and demonstrated reversable ductal shunting only. Survival in this group was 97%. Only four patients out of 58 exhibited the "honeymoon period," with a period of stability followed by severe ductal shunting. Arterial CO2 accurately reflects the degree of lung development in this disease and separates those patients with severe pulmonary hypoplasia, where the outcome is invariably fatal, from those with a well-developed contralateral lung where there is excellent potential for survival.

Carbon Dioxide↗
PubMed1999

Cloning and expression pattern of a mouse homologue of drosophila sprouty in the mouse embryo.

Signaling molecules belonging to the Fibroblast growth factor (Fgf) family are necessary for directing bud outgrowth during tracheal development in Drosophila and lung development in mouse. A potential inhibitor of the Fgf signaling pathway, called Sprouty, has been identified in Drosophila. We have identified three potential mouse homologues of sprouty. One of them, called Sprouty4, exhibits a very restricted expression pattern. At 8.0 dpc (days post coitum) Sprouty4 is strongly expressed in the primitive streak region. At 9. 5 and 10.5 dpc, Sprouty4 is expressed in the nasal placode, the maxillary and mandibular processes, the otic vesicule, the second branchial arch, in the progress region of the limb buds and the presomitic mesoderm. Sprouty4 expression is also detected in the lateral region of the somites. In the developing lung, Sprouty4 is expressed broadly in the distal mesenchyme.

Amino Acid Sequence↗
PubMed2004

Papillary thyroid carcinomas with lung metastases.

BACKGROUND: Limited information is available on the presentation, treatment outcomes, and prognostic factors of papillary thyroid carcinoma with lung metastases. METHODS: This study retrospectively analyzed the data of 2003 patients with thyroid cancer who were treated and followed up at Chang Gung Memorial Hospital from January 1979 to December 2002. In total, 1516 papillary thyroid carcinomas were enrolled. One hundred two (6.7%) papillary thyroid carcinomas with lung metastases were followed including 57 women with mean age of 41.7 +/- 17.3 years and 45 men with mean age of 49.6 +/- 17.2 years. These patients included 52 patients with papillary thyroid carcinoma who presented with lung metastases at the time of diagnosis. The 102 cases of papillary thyroid carcinomas with lung metastases included 72 cases with lung metastases only, and 30 cases with other organ involvement. RESULTS: After mean follow-up periods of 8.8 +/- 0.6 years, 28 (27.5%) of the patients with lung metastasis died, while 6 improved to clinical stage I. The 5-, 10-, 15-, and 20-year survival rates in patients with papillary thyroid carcinoma without distant metastasis and in the lung metastases groups were 99.0%, 98.5%, 98.0%, 98.0%, and 91.3%, 75.0%, 64.0%, 51.2%, respectively. Comparing the Kaplan-Meier survival curves between the patients with papillary thyroid carcinomas with lung metastases only and those with multiorgan metastases demonstrates no statistically significant difference in mortality rates. However, age, gender, postoperative thyroglobulin (Tg) level and tumor size displayed statistically significant differences between the lung metastases and no distant metastasis groups. Fifty of the 102 patients with papillary thyroid carcinomas with lung metastases developed lung metastases during follow-up. Larger amounts of remnant thyroid tissues with higher Tg levels were noted in these patients compared to those without distant metastasis. CONCLUSIONS: The prognosis of patients with papillary thyroid carcinoma with lung metastases at time of diagnosis is the same as for those whose lung metastases are discovered later. Survival analysis demonstrates no difference between lung metastases and multiorgan metastases.

Adult↗
PubMed2005

Conditional recombination reveals distinct subsets of epithelial cells in trachea, bronchi, and alveoli.

To identify relationships amongst tracheal and alveolar epithelial cells during lung development, we used conditional systems controlled by the rat CCSP and human SFTPC gene promoters to express Cre-recombinase in the developing mouse lung, thereby permanently labeling cells by expression of alkaline phosphatase or green fluorescent protein. When controlled by the rat CCSP promoter, continuous exposure of the fetus to doxycycline caused widespread recombination in conducting airway epithelial cells, including cells of the trachea, bronchi, and bronchioles before birth, and in both conducting and peripheral airways after birth. Neuroepithelial cells, identified by CGRP staining, were never labeled. Recombination and permanent labeling were observed in both ciliated and nonciliated respiratory epithelial cells, demonstrating their derivation from common progenitor cells during lung morphogenesis. Remarkable dorsal-ventral and cephalo-caudal labeling patterns, established before birth, were identified by recombination controlled by the rat CCSP gene promoter. In the trachea, subsets of epithelial cells labeled by the CCSP promoter were organized horizontally along the dorsal-ventral axis of the trachea, where selective labeling of cells juxtaposed to tracheal and bronchial cartilage was observed. In sharp contrast, recombination controlled by the human SFTPC gene promoter identified related cells that were organized in linear patterns along the cephalo-caudal axis of the conducting airways. Conditional expression of Cre-recombinase in the respiratory epithelium provides a useful model for the study of gene expression and function in the mouse respiratory tract and in the lung.

Animals↗
PubMed2006

Impact of the loss of Hoxa5 function on lung alveogenesis.

The involvement of genes controlling embryonic processes in the etiology of diseases often escapes attention because of the focus given to their inherent developmental role. Hoxa5 belongs to the Hox gene family encoding transcription factors known for their role in skeletal patterning. Hoxa5 is required for embryonic respiratory tract morphogenesis. We now show that the loss of Hoxa5 function has severe repercussions on postnatal lung development. Hoxa5-/- lungs present an emphysema-like morphology because of impaired alveogenesis. Chronic inflammation characteristics, including goblet cell hyperplasia, mucus hypersecretion, and recruitment of inflammatory cells, were also observed. Altered cell specification during lung morphogenesis triggered goblet cell anomalies. In addition, the defective motility of alveolar myofibroblast precursors in the embryonic lung led to the mispositioning of the alveolar myofibroblasts and to abnormal elastin deposition postnatally. Both goblet cell hyperplasia and elastic fiber abnormalities contributed to the chronic physiopathological features of Hoxa5-/- lungs. They constituted an attractive stimulus to recruit activated macrophages that in turn generated a positive feedback loop that perpetuated macrophage accumulation in the lung. The present work corroborates the notion that altered Hox gene expression may predispose to lung pathologies.

Animals↗
PubMed2006

Integrin-mediated transforming growth factor-beta activation regulates homeostasis of the pulmonary epithelial-mesenchymal trophic unit.

Trophic interactions between pulmonary epithelial and mesenchymal cell types, known as the epithelial-mesenchymal trophic unit (EMTU), are crucial in lung development and lung disease. Transforming growth factor (TGF)-beta is a key factor in mediating these interactions, but it is expressed in a latent form that requires activation to be functional. Using intact fetal tracheal tissue and primary cultures of fetal tracheal epithelial cells and fibroblasts, we demonstrate that a subset of integrins, alpha(v)beta(6) and alpha(v)beta(8), are responsible for almost all of the TGF-beta activation in the EMTU. Both alpha(v)beta(8) and alpha(v)beta(6) contribute to fetal tracheal epithelial activation of TGF-beta, whereas only alpha(v)beta(8) contributes to fetal tracheal fibroblast activation of TGF-beta. Interestingly, fetal tracheal epithelial alpha(v)beta(8)-mediated TGF-beta activation can be enhanced by phorbol esters, likely because of the increased activity of MT1-MMP, an essential co-factor in alpha(v)beta(8)-mediated activation of TGF-beta. Autocrine alpha(v)beta(8)-mediated TGF-beta activation by fetal tracheal fibroblasts results in suppression of both transcription and secretion of hepatocyte growth factor, which is sufficient to affect phosphorylation of the airway epithelial hepatocyte growth factor receptor, c-Met, as well as airway epithelial proliferation in a co-culture model of the EMTU. These findings elucidate the function and complex regulation of integrin-mediated activation of TGF-beta within the EMTU.

Antigens, Neoplasm↗
PubMed1990

Four cases of lung cancer associated with idiopathic interstitial pneumonia.

It is well known that lung cancer develops frequently in patients with idiopathic interstitial pneumonia (IIP) (9.8-22.8%). We investigated 4 patients who developed lung cancer among the 28 patients with IIP (14.3%) who were admitted to our hospital from June 1981 to March 1989. Many reports have pointed out the clinical features of lung cancer associated with IIP as male sex, old age, heavy smoking, and poor prognosis. Our 4 series were agreed with these clinical features. Lung cancer associated with IIP have been often reported to occur in the lower and peripheral regions of the lung, and honeycomb structures are frequently seen. But we found that lung cancer in IIP could actually occur in both the lower and upper regions of the lung and does not occur only in the honeycomb structures. There was no obvious dominance of any histological type among the tumors. If lung cancer is suspected in a patient with IIP, tumor markers are of some value for diagnosis, but are not sensitive enough to be used alone.

Adenocarcinoma↗
PubMed2001

Hypomethylation of p53 in peripheral blood DNA is associated with the development of lung cancer.

Alterations in DNA methylation have been associated with cancers at almost all tumor sites and represent one of the most consistent changes in neoplastic cells. The underlying etiological mechanisms for alteration of DNA methylation patterns are not understood, but experimental studies in animals suggest potential environmental and genetic influences. The purpose of this study was to investigate whether DNA hypomethylation in peripheral blood DNA (potentially representing status at the lung) was associated with increased risk for the development of lung cancer. We evaluated genome-wide and p53 gene-specific hypomethylation in 100 lung cancer cases and controls selected from a large clinical trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Genome-wide methylation status was assessed using the in vitro methyl acceptance capacity assay and p53 gene-specific methylation status using the HpaII quantitative PCR assay. Hypomethylation was evaluated as a risk factor using multivariate conditional logistic regression analyses. Genome-wide methylation status was unrelated to lung cancer risk; the odds ratio was 1.25 and the 95% confidence interval was 0.48-3.21 for those in the highest versus lowest quartile of hypomethylation status. Hypomethylation of the p53 gene in exons 5-8, the hypermutable region, was associated with a 2-fold increased risk for lung cancer (odds ratio, 2.20; 95% confidence interval, 1.04-4.65), whereas there was no risk increase for hypomethylation at exons 2-4, a region of the gene not known for its mutability or functional significance in cancer. Our results indicate that hypomethylation status within exons 5-8 of p53 from peripheral lymphocyte DNA may be a relevant predictor of lung cancer among male smokers.

Aged↗
PubMed2002

Bronchopulmonary dysplasia and chronic lung disease of infancy: strategies for prevention and management.

Remarkable advances in the treatment of neonatal respiratory disorders, such as antenatal glucocorticoid therapy, surfactant replacement therapy and alternative modes of ventilation, have reduced neonatal mortality and acute respiratory morbidity. However, bronchopulmonary dysplasia and chronic lung disease of infancy remain a substantial complication, especially among the most immature infants. The pathogenesis of chronic lung disease is complex and multifactorial. Prevention and treatment will require a comprehensive multiprong approach with specific interventions and practices focused on different levels of the pathways leading to chronic lung changes. Future improvements in care will require a better understanding of lung development and lung repair mechanisms. However, the ultimate and most effective approach should be a relentless pursuit for measures to prevent premature births.

Bronchopulmonary Dysplasia↗
PubMed1992

[Measurement of T-lymphocyte subsets in bronchial alveolar lavage fluid on smokers and patients with lung cancer].

The measurements of T-lymphocyte subsets (as expressed by, CD3 CD4 and CD8) in the peripheral blood and bronchial alveolar lavage fluid (BALF) on 30 cases of lung cancer, 26 cases of smoker and 25 cases of nonsmoker have been done. The results showed that there existed no differences in the peripheral blood of the above said subsets of lymphocyte. In BALF the percentage of CD3 in all the lymphocytes did not show any significant difference among the three tested groups, either (P > 0.05). But the percentage of CD4 and the ratio of CD4/CD8 manifested the following peculiarity: patients with lung cancers < smokers < nonsmokers (P < 0.01). On the contrary, the percentage of CD8 showed just the opposite: patients with lung cancer > smokers nonsmokers (P < 0.01). It was suggested that the cellular immunity as shown in the peripheral blood did not correspond with the findings in the BALF. The cellular immunity of the lungs was decreased both in patients with lung cancer and smokers, but more severely in the group of lung cancer patients. Smokers who have had changes of above said subsets of lymphocytes in the lungs may develop lung cancer. As the lung cancer advances, it may suppress body immunity and in turn enhance the cancer growth. Both the cause and the effect are interrelated. Therefore, the provocative agents for cellular immunity may act as one of the adjunctive therapies for patients with lung cancer. Giving up smoking should play an important role in recovering or promoting the immunity of the lungs and decreasing the incidence as well as improving the prognosis in patients with lung cancer.

Adult↗
PubMed1998

Transcription of a novel mouse semaphorin gene, M-semaH, correlates with the metastatic ability of mouse tumor cell lines.

In the attempt to identify genes associated with metastasis, we have compared gene expressions of two metastatic cell lines, 4T1 and 66cl4, and one noninvasive, nonmetastatic cell line, 67NR, which originate from the same mouse mammary adenocarcinoma. Using the technique of differential display, we identified a novel member of the semaphorin/collapsin family in the two metastatic cell lines. We have named it M-semaH. Northern hybridization to a panel of tumor cell lines revealed transcripts in 12 of 12 metastatic cell lines but in only 2 of 6 nonmetastatic cells and none in immortalized mouse fibroblasts. To our knowledge, this is the first time that the expression of a semaphorin gene has been shown to correlate positively with tumor progression. We have characterized two transcripts present in the tumor cells. One transcript, M-semaH-v, is a putative splice variant, which is less abundant in normal tissue and lacks 478 bp in the 3' untranslated region. Both transcripts encode the same 775 amino acids with the features of a secreted glycoprotein. Northern analysis suggests that the M-semaH gene is involved in embryonic development and in situ hybridization locates the M-semaH expression to the developing lungs, to developing skeletal elements, and to the ventral horns of the developing neural tube.

Amino Acid Sequence↗
PubMed1996

The connective tissue compartment in the terminal region of the developing rat lung. An ultrastructural study.

The present study was designed to analyze the connective tissue compartment in the terminal region of the developing rat lung. Lungs of rat fetuses (at 17, 19 and 21 days of gestation) and of newborns (2, 4, 7, 10, 14 and 21 days after birth) were examined by several ultrastructural techniques; staining with tannic acid for elastic fibers (EFs), collagen fibers (CFs) and basement membranes (BMs); staining with ruthenium red for glycosaminoglycans; and immunoelectron microscopy for visualization of collagen type IV, laminin and fibronectin (FN). Dynamic changes in the levels and distribution of the components of the extracellular connective tissue were observed in parallel with the formation and maturation of the alveoli. The terminal regions of the respiratory tract of the rat fetus and of the lungs of early newborns contained few CFs and EFs, and the Bms in these lungs were incomplete. However, strong immunolabeling of FN was observed (in BMs, CFs and in spaces among fibroblasts). Starting from 4 to 7 days newborns had increasing numbers of Cfs and EFs and BMs became more extensive. In rat newborns, immunolabeling specific for FN was weak and irregularly distributed. Furthermore, the present results provide a summary of the changes in connective tissue that occur in the rat lung during different stages of its development, from the pseudoglandular stage, through the canalicular and saccular stages, to the alveolar stage.

Animals↗
PubMed2006

Haplotypes in matrix metalloproteinase gene cluster on chromosome 11q22 contribute to the risk of lung cancer development and progression.

PURPOSE: Matrix metalloproteinases (MMP) play important roles in cancer development and single nucleotide polymorphisms (SNP) in some MMP genes were shown to confer susceptibility to certain cancers. This study examined the association between genotypes and haplotypes in the MMP1-MMP3-MMP12 gene cluster and risk of lung cancer development and metastasis. EXPERIMENTAL DESIGN: A two-stage investigation was conducted. First, 35 SNPs covering these genes were selected and validated in 190 patients and 190 controls. Twenty-two validated SNPs were then analyzed in an entire case-control panel consisting of 711 patients and 716 controls. Associations with the risk of lung cancer were estimated by logistic regression. RESULTS: The investigated MMP gene region could be partitioned into two major haplotype blocks. One common haplotype in the block composed of major part of MMP1 transcription region was significantly associated with increased risk for the development [odds ratio (OR), 1.35; 95% confidence interval (95% CI), 1.11-1.63; P = 0.01; permutated P = 0.134] and distant metastasis of lung cancer (ORs for stage IV versus stages I-III, 1.67; 95% CI, 1.12-2.50; P = 0.009; permutated P = 0.048) and the other showed a protective effect against metastasis (ORs for stage IV versus stages I-III, 0.22; 95% CI, 0.07-0.62; P = 0.001; permutated P = 0.011). Another common haplotype in the block across MMP3 was significantly associated with decreased risk for developing lung cancer (OR, 0.71; 95% CI, 0.59-0.86; P = 0.003; permutated P = 0.027). CONCLUSIONS: The observed multiple cancer-associated genetic variants suggested that the MMP1-MMP3-MMP12 gene cluster plays important roles in lung cancer development and progression.

Adult↗
PubMed1988

Muscarinic cholinergic receptors in lung of developing rats.

The muscarin-specific radioligand 1-quinuclidinyl-[phenyl-4-3H]-benzilate was used to determine the development of muscarinic receptors in particulate membranes of rat lung. Postnatal development is associated with a decrease in the number of binding sites (Bmax). Bmax was 65.61 +/- 11.33 fmol/mg protein in 21-day-old rat fetuses and it decreased to 36.64 +/- 10.18 at postnatal day 1, 32.37 +/- 4.99 at day 7 and 16.15 +/- 4.13 fmol/mg protein at 2 months. Bmax at 2 months was significantly different from all the others (Dunnett's test). The dissociation constant Kd was 0.25 nM in 2-month-old animals and it did not undergo significant changes during development.

Aging↗
PubMed2005

Stimulation of HIF-1alpha, HIF-2alpha, and VEGF by prolyl 4-hydroxylase inhibition in human lung endothelial and epithelial cells.

Diminished alveolar and vascular development is characteristic of bronchopulmonary dysplasia (BPD) affecting many preterm newborns. Hypoxia promotes angiogenic responses in developing lung via, for example, vascular endothelial growth factor (VEGF). To determine if prolyl 4-hydroxylase (PHD) inhibition could augment hypoxia-inducible factors (HIFs) and expression of angiogenic proteins essential for lung development, HIF-1alpha and -2alpha proteins were assessed in human developing and adult lung microvascular endothelial cells and alveolar epithelial-like cells treated with either the HIF-PHD-selective inhibitor PHI-1 or the nonselective PHD inhibitors dimethyloxaloylglycine (DMOG) and deferoxamine (DFO). PHI-1 stimulated HIF-1alpha and -2alpha equally or more effectively than did DMOG or DFO, enhanced VEGF release, and elevated glucose consumption, whereas it was considerably less cytotoxic than DMOG or DFO. Moreover, VEGF receptor Flt-1 levels increased, whereas KDR/Flk-1 decreased. PHI-1 treatment also increased PHD-2, but not PHD-1 or -3, protein. These results provide proof of principle that HIF stimulation and modulation of HIF-regulated angiogenic proteins through PHI-1 treatment are feasible, effective, and nontoxic in human lung cells, suggesting the use of PHI-1 to enhance angiogenesis and lung growth in evolving BPD.

Basic Helix-Loop-Helix Proteins↗
PubMed1982

Diffusing capacity in idiopathic scoliosis and its interpretation regarding alveolar development.

We measured lung volumes, diffusing capacity by the single breath method (DL), membrane permeability (DM), and capillary blood volume (Vc) in 22 subjects with idiopathic scoliosis (mean angle of curvature, 66 degrees). Compared with an age-matched group, vital capacity, total lung capacity, and functional residual capacity were respectively, 21% (p less than 0.0001), 18% (p less than 0.01), and 15% (p less than 0.05) lower. The DL was 17% lower (p less than 0.01), but specific DL (DL divided by alveolar volume = DLVA) was the same. For both groups, DLVA was inversely correlated with VA. The same qualitative relationship existed between DM, Vc, their specific values, and VA except for a larger spread of Vc in the scoliotic group. The data show that DL and its components, DM and Vc, are normal in idiopathic scoliosis when reduced lung volumes are allowed for. These findings are consistent with partial failure of alveolar enlargement as a result of the thoracic deformity rather than any atrophy of the alveoli or pulmonary vasculature. Thus scoliosis results in a delay of lung development, such that in a group of symptomatic patients with moderate degrees of deformity (mean angle of curvature, 66 degrees), lung volumes and DL are about 80% of that of an age-matched control group; the alveolar characteristics of a 12-yr-old with scoliosis are therefore similar to those of a 9-yr-old normal child.

Adolescent↗
PubMed2002

Screening for second primary lung cancer after treatment of laryngeal cancer.

OBJECTIVES/HYPOTHESIS: As a result of smoking, patients who have received curative treatment for laryngeal cancer run a high risk of developing lung cancer. Therefore, these patients enter a screening program that aims to detect lung cancer at an asymptomatic stage. The study evaluated whether screening for lung cancer by means of regular chest x-ray examinations contributed to prolonging survival. STUDY DESIGN: A longitudinal follow-up study was performed to analyze the survival of patients who had received curative treatment for squamous cell laryngeal cancer and developed lung cancer during the follow-up period. METHODS: Patients with lung cancer were divided into two groups: 1) patients with asymptomatic screen-detected lung cancer and 2) patients with complaints indicating lung cancer, whose tumor was detected in the interval between screening examinations by chest x-ray films. RESULTS: In the complete group of patients with laryngeal cancer, no prognostic factors could be identified for developing lung cancer. There was no prolongation of survival in the screen-detected asymptomatic lung cancer patients. The median survival of both groups was 56 months (P =.57). The date of detection of the lung cancer was clearly brought forward by screening; a difference of 8 months was found between the median detection date of the two groups (P <.001). There was no difference in tumor-specific mortality between the two groups. CONCLUSION: Screening by chest x-ray examination to detect lung cancer in an asymptomatic stage after curative treatment for squamous cell laryngeal cancer does not improve survival for patients who develop lung cancer.

Adult↗