Evidence for adult lung growth in humans

A 33-year-old woman underwent a right-sided pneumonectomy in 1995 for treatment of a lung adenocarcinoma. As expected, there was an abrupt decrease in her vital capacity, but unexpectedly, it increased during the subsequent 15 years. Serial computed tomographic (CT) scans showed progressive enlargement of the remaining left lung and an increase in tissue density. Magnetic resonance imaging (MRI) with the use of hyperpolarized helium-3 gas showed overall acinar-airway dimensions that were consistent with an increase in the alveolar number rather than the enlargement of existing alveoli, but the alveoli in the growing lung were shallower than in normal lungs. This study provides evidence that new lung growth can occur in an adult human

Sitting and Supine Esophageal Pressures in Overweight and Obese Subjects Authors

Esophageal pressure can be used to approximate pleural pressure and might be clinically useful, particularly in the obese e.g to guide mechanical ventilator settings in critical illness. However, mediastinal artifact (the difference between true pleural pressure and esophageal pressure) may limit acceptance of the measurement, and reproducibility of esophageal pressure measurements remains unknown. Therefore, we aimed to assess the effect of body posture on esophageal pressure in a cohort of obese but healthy subjects, some of whom had multiple measurements, to address the clinical robustness of esophageal manometry. Twenty-five overweight and obese subjects (BMI>25kg/m2) and 11 control lean subjects (BMI<25kg/m2) underwent esophageal manometry with pressures measured seated and supine. Twenty overweight and obese subjects had measurements repeated after ~1-2 weeks. Anthropometric data and sitting and supine spirometry were recorded. The average end-expiratory esophageal pressures sitting and supine were greater in the overweight and obese group than the lean group (sitting −0.1±2.1 vs. −3.3±1.2cmH2O, supine 9.3±3.3 vs. 6.9±2.8cmH2O, respectively). The mean differences between repeated measurements were small (−0.3 ± 1.7cmH2O sitting and −0.1 ± 1.5cmH2O supine). Esophageal pressures correlated with a number of anthropometric and spirometric variables. In conclusion, esophageal pressures are slightly greater in overweight and obese subjects than lean subjects; but changes with position are similar in both groups. These data indicate that mediastinal weight and postural effects on esophageal pressure are within a clinically acceptable range, and suggest that esophageal manometry can be used to inform clinical decision making across wide range of body types

Evidence for Adult Lung Growth in Humans

A 33-year-old woman underwent a right-sided pneumonectomy in 1995 for treatment of a lung adenocarcinoma. As expected, there was an abrupt decrease in her vital capacity, but unexpectedly, it increased during the subsequent 15 years. Serial computed tomographic (CT) scans showed progressive enlargement of the remaining left lung and an increase in tissue density. Magnetic resonance imaging (MRI) with the use of hyperpolarized helium-3 gas showed overall acinar-airway dimensions that were consistent with an increase in the alveolar number rather than the enlargement of existing alveoli, but the alveoli in the growing lung were shallower than in normal lungs. This study provides evidence that new lung growth can occur in an adult human

Manacled to Identity: Cosmopolitanism, Class, and ‘The Culture Concept’ in Stephen Crane

This article begins with a close reading of Stephen Crane’s short story ‘Manacled’ from 1900, which situates this rarely considered short work within the context of contemporary debates about realism. I then proceed to argue that many of the debates raised by the tale have an afterlife in our own era of American literary studies, which has frequently focused on questions of ‘identity’ and ‘culture’ in its reading of realism and naturalism to the exclusion of the importance of cosmopolitan discourses of diffusion and exchange across national borders. I then offer a brief reading of Crane’s novel George’s Mother, which follows Walter Benn Michaels in suggesting that the recent critical attention paid to particularities of cultural difference in American studies have come to conflate ideas of class and social position with ideas of culture in ways that have ultimately obscured the presence of genuine historical inequalities in US society. In order to challenge this critical commonplace, I situate Crane’s work within a history of transatlantic cosmopolitanism associated with the ideas of Franz Boas and Matthew Arnold to demonstrate the ways in which Crane’s narratives sought out an experience of the universal within their treatments of the particular

Sixty Years of Modern Human Origins in the American Anthropological Association

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65197/1/aa.2003.105.1.89.pd

Epigenetic Characterization of the FMR1 Gene and Aberrant Neurodevelopment in Human Induced Pluripotent Stem Cell Models of Fragile X Syndrome

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. In addition to cognitive deficits, FXS patients exhibit hyperactivity, attention deficits, social difficulties, anxiety, and other autistic-like behaviors. FXS is caused by an expanded CGG trinucleotide repeat in the 5′ untranslated region of the Fragile X Mental Retardation (FMR1) gene leading to epigenetic silencing and loss of expression of the Fragile X Mental Retardation protein (FMRP). Despite the known relationship between FMR1 CGG repeat expansion and FMR1 silencing, the epigenetic modifications observed at the FMR1 locus, and the consequences of the loss of FMRP on human neurodevelopment and neuronal function remain poorly understood. To address these limitations, we report on the generation of induced pluripotent stem cell (iPSC) lines from multiple patients with FXS and the characterization of their differentiation into post-mitotic neurons and glia. We show that clones from reprogrammed FXS patient fibroblast lines exhibit variation with respect to the predominant CGG-repeat length in the FMR1 gene. In two cases, iPSC clones contained predominant CGG-repeat lengths shorter than measured in corresponding input population of fibroblasts. In another instance, reprogramming a mosaic patient having both normal and pre-mutation length CGG repeats resulted in genetically matched iPSC clonal lines differing in FMR1 promoter CpG methylation and FMRP expression. Using this panel of patient-specific, FXS iPSC models, we demonstrate aberrant neuronal differentiation from FXS iPSCs that is directly correlated with epigenetic modification of the FMR1 gene and a loss of FMRP expression. Overall, these findings provide evidence for a key role for FMRP early in human neurodevelopment prior to synaptogenesis and have implications for modeling of FXS using iPSC technology. By revealing disease-associated cellular phenotypes in human neurons, these iPSC models will aid in the discovery of novel therapeutics for FXS and other autism-spectrum disorders sharing common pathophysiology.FRAXA Research FoundationHarvard Stem Cell Institute (seed grant)Stanley Medical Research InstituteNational Institute of Mental Health (U.S.) (grant #R33MH087896