Prenatal administration of retinoic acid upregulates insulin-like growth factor receptors in the nitrofen-induced hypoplastic lung

BACKGROUND : Pulmonary hypoplasia (PH) is the main cause of mortality in newborns with congenital diaphragmatic hernia (CDH). Prenatal administration of retinoic acid (RA) stimulates alveologenesis in the nitrofen‐induced pulmonary hypoplasia. Insulin‐like growth factor receptors (IGFRs) play a crucial role in alveologenesis during lung development. We recently demonstrated that IGFRs were downregulated in later stages of lung development in the nitrofen CDH model. Several studies suggest the ability of RA to regulate insulin‐like growth factor signaling. We hypothesized that IGFRs pulmonary gene expression is upregulated after the administration of RA in the nitrofen‐induced CDH model. METHODS : Pregnant rats were exposed to either olive oil or nitrofen on day 9 (D9) of gestation. RA was given intraperitoneally on days D18, D19, and D20. Fetal lungs were dissected on D21 and divided into control, control + RA, CDH, and CDH + RA group. IGFRs gene and protein expression were determined using RT‐PCR and immunohistochemistry. RESULTS : mRNA expression levels of IGFRs were significantly increased in control + RA and CDH + RA compared with CDH group. Immunoreactivity of IGFRs was markedly increased in control + RA and CDH + RA compared with CDH lungs. CONCLUSIONS : Upregulation of pulmonary gene and protein expression of IGFRs after prenatal RA treatment in the nitrofen model suggests that RA may promote lung growth by stimulating IGFRs mediated alveologenesis. Birth Defects Res (Part B) 92:148–151, 2011. © 2011 Wiley‐Liss, Inc.     

Stem cells and repair of lung injuries

Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung.     

Early childhood stress and adult age mortality--a study of dental enamel hypoplasia in the medieval Danish village of Tirup

This study explores how linear enamel hypoplasia (LEH) affects mortality in the village of Tirup (A.D. 1150-1350), Denmark. Data consist of information on 583 skeletons aged 1 year or more. Three partly overlapping subsamples were defined. (1) 104 skeletons of young children aged 1-6 years and 120 skeletons of adults giving information on LEH. (2) 458 skeletons aged 6 years or more. (3) 109 adult skeletons (aged 20 years or more) that provided transition analysis age estimates, sex assessments, and LEH information. Of the 109 skeletons in Subsample 3, 60 had no and 49 had at least one LEH. In Subsample 1, it was found that the case fatality rate for episodes potentially leading to LEH dropped from over 0.5 in 1-year olds to around 0.1 in 3-5-year olds. Only models with heterogeneity of frailty could describe late childhood and adolescent mortality. Further, it was shown that only a model with continuously varying frailty preserved heterogeneity to adulthood. Among young adult females and males in all adult ages, people with LEH experienced a higher mortality than people without it. Among males, the mortality rate ratio (MRR) was 2.28. The analyses indicate that the MRR gives an unbiased estimate for the extra risk of dying for adult males with LEH. The values of the case fatality rates for young children might be slightly biased upward because of a higher than average number of older children and adolescents dying with LEH.     

Gross enamel hypoplasia in molars from subadults in a 16th-18th century London graveyard

Dental Enamel Hypoplasia has long been used as a common nonspecific stress indicator in teeth from archaeological samples. Most researchers report relatively minor linear and pitted hypoplastic defects on tooth crown surfaces. In this work we report a high prevalence and early age of onset of extensive enamel defects in deciduous and permanent molars in the subadults from the post-medieval cemetery of Broadgate, east central London. Analysis of the dentition of all 45 subadults from the cemetery, using both macroscopic and microscopic methods, reveals disturbed cusp patterns and pitted, abnormal and arrested enamel formation. Forty-one individuals from this group (93.2%) showed some evidence of enamel hypoplasia, 28 of them showing moderate or extensive lesions of molars, deciduous or permanent (63.6% of the sample). Scanning Electron Microscope images reveal many molars with grossly deformed cuspal architecture, multiple extra cusps and large areas of exposed Tomes' process pits, where the ameloblasts have abruptly ceased matrix production, well before normal completion. This indented, rough and poorly mineralized surface facilitates both bacterial adhesion and tooth wear, and when such teeth erupt fully into the mouth they are likely to wear and decay rapidly. We suggest that this complex combination of pitted and plane-form lesions, combined with disruption of cusp pattern and the formation of multiple small cusps, should henceforth be identified as "Cuspal Enamel Hypoplasia."     

Hardships of contact: Enamel hypoplasias in Tupí-Mondé Amerindians from the Brazilian Amazonia

This paper presents an assessment of enamel defects (hypoplasias) in the permanent anterior teeth of three Tupí-Mondé-speaking groups from the Brazilian Amazonia: the Gavião, Suruí, and Zoró. These are native societies that experienced the onset of permanent contact with Brazilian national society in different periods of the 20th century. Tupí-Mondé dentition is highly hypoplastic, which is possibly related to exposure to adverse health and nutritional conditions. Data for the Gavião, Suruí, and Zoró are in agreement with results from other populations that show that certain teeth, the maxillary central incisors and the mandibular canines in particular, tend to be more hypoplastic. Although all types of teeth show hypoplasia concentrations at some enamel zones, there is substantial intertooth variation in the age at which peaks occur. It is argued that hypoplasia concentrations at certain ages are unlikely to be related to postweaning stresses for the Tupí-Mondé. Statistically significant associations between presence of enamel defects and deficits in physical growth (height-for-age) were detected in children 7–11 years of age. Diachronic assessment of enamel defects, which rested upon the potential of enamel as “memory” of past periods of systemic physiological perturbation, allowed us to unravel aspects related to the dynamics of Tupí-Mondé life during the 20th century. Frequencies of enamel zones with defects peaked during the contact years of each of the Tupí-Mondé groups, attesting to the extreme social and biological hardships that characterized the contact experiences of these native societies with Brazilian national society. Am J Phys Anthropol 109:111–127, 1999. © 1999 Wiley-Liss, Inc.     

Intertooth patterns of hypoplasia expression: Implications for childhood health in the Classic Maya collapse

Enamel hypoplasias, which record interacting stresses of nutrition and illness during the period of tooth formation, are a key tool in the study of childhood health in prehistory. But interpretation of the age of peak morbidity is complicated by differences in susceptibility to stress both between tooth positions and within a single tooth. Here, hypoplasias are used to evaluate the prevailing ecological model for the collapse of Classic Period Lowland Maya civilization, circa AD 900. Hypoplasias were recorded in the full dentition of 160 adult skeletons from six archaeological sites in the Pasión River region of Guatemala. Instead of constructing a composite scale of stress experience, teeth are considered separately by position in the analysis. No statistical differences are found in the proportion of teeth affected by hypoplasia between “Early,” Late Classic, and Terminal Classic Periods for anterior teeth considered to be most susceptible to stress, indicating stability in the overall stress loads affecting children of the three chronological periods. However, hypoplasia trends in posterior teeth may imply a change in the ontogenetic timing of more severe stress episodes during the final occupation and perhaps herald a shift in child-care practices. These results provide little support for the ecological model of collapse but do call to attention the potential of posterior teeth to reveal subtle changes in childhood morbidity when considered individually. Am J Phys Anthropol 102:233–247, 1997 © 1997 Wiley-Liss, Inc.     

Discrepancy in compliance between the clinical and genetic diagnosis of choroidal hypoplasia in Danish Rough Collies and Shetland Sheepdogs

Collie eye anomaly (CEA) is a congenital, inherited ocular disorder which is widespread in herding breeds. Clinically, the two major lesions associated with CEA are choroidal hypoplasia (CH) and coloboma, and both lesions are diagnosed based on ophthalmological examination. A 7.8‐kb intronic deletion in the gene encoding non‐homologous end‐joining factor 1 (NHEJ1) has been reported to be the causative mutation underlying CH when present in the homozygous state. In this study, we have investigated the compliance between the clinical and genetic diagnosis of CH in the Danish Rough Collie and Shetland Sheepdog populations. Our results show that the deletion in NHEJ1 is not predictive for CH in the Danish Rough Collie population, whereas the clinical and genetic diagnosis is in accordance with each other in the Shetland Sheepdog population. Based on these results, it can be concluded that the intronic deletion in NHEJ1 is not the causative mutation but, rather, a marker linked to the locus underlying the trait in some populations but linked to both the wild‐type and CH‐causing locus in most dogs in the Danish Rough Collie population.