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Cincinnati, OH, United States

Rawlins E.L.,University of Cambridge | Perl A.-K.,Perinatal Institute
American Journal of Respiratory Cell and Molecular Biology | Year: 2012

The purpose of this review is to give a comprehensive overview of transgenicmouselines suitablefor studyinggenefunctionandcellular lineage relationships in lung development, homeostasis, injury, and repair. Many of the mouse strains reviewed in this Perspective have been widely shared within the lung research community, and new strains are continuously being developed. There aremany transgenic lines that target subsets of lung cells, but it remains a challenge for investigators to select the correct transgenic modules for their experiment. This review covers the tetracycline- and tamoxifeninducible systems and focuses on conditional lines that target the epithelial cells. We point out the limitations of each strain so investigators can choose the system that will work best for their scientific question. Current mesenchymal and endothelial lines are limited by the fact that they are not lung specific. These lines are summarized in a brief overview. In addition, useful transgenic reporter mice for studying lineage relationships, promoter activity, and signaling pathways will complete our lung-specific conditional transgenic mouse shopping list. Copyright ©2012 by the American Thoracic Society.


Namekawa S.H.,Perinatal Institute
Journal of visualized experiments : JoVE | Year: 2014

During testicular germ cell differentiation, the structure of nuclear chromatin dynamically changes. The following describes a method designed to preserve the three-dimensional chromatin arrangement of testicular germ cells found in mice; this method has been termed as the three-dimensional (3D) slide method. In this method, testicular tubules are directly treated with a permeabilization step that removes cytoplasmic material, followed by a fixation step that fixes nuclear materials. Tubules are then dissociated, the cell suspension is cytospun, and cells adhere to slides. This method improves sensitivity towards detection of subnuclear structures and is applicable for immunofluorescence, DNA, and RNA fluorescence in situ hybridization (FISH) and the combination of these detection methods. As an example of a possible application of the 3D slide method, a Cot-1 RNA FISH is shown to detect nascent RNAs. The 3D slide method will facilitate the detailed examination of spatial relationships between chromatin structure, DNA, and RNA during testicular germ cell differentiation.


Gardosi J.,Perinatal Institute
Journal of Obstetrics and Gynaecology Canada | Year: 2014

Customized growth charts reduce complexity in antenatal care for the expectant mother and her clinicians by improving the distinction between physiological and pathological variation in fetal size. Their application in large databases has improved our understanding of the importance of intrauterine growth restriction and its antenatal recognition. Their implementation into clinical practice, together with the appropriate training and referral protocols, has been shown to reduce the risk of stillbirth. © 2014 Society of Obstetricians and Gynaecologists of Canada.


Perl A.-K.T.,Perinatal Institute | Riethmacher D.,University of Southampton | Whitsett J.A.,Perinatal Institute
American Journal of Respiratory and Critical Care Medicine | Year: 2011

Rationale: The respiratory epithelium has a remarkable capacity to respond to acute injury. In contrast, repeated epithelial injury is often associated with abnormal repair, inflammation, and fibrosis. There is increasing evidence that nonciliated epithelial cells play important roles in the repair of the bronchiolar epithelium after acute injury. Cellular processes underlying the repair and remodeling of the lung after chronic epithelial injury are poorly understood. Objectives: To identify cell processes mediating epithelial regeneration and remodeling after acute and chronic Clara cell depletion. Methods: A transgenic mouse model was generated to conditionally express diphtheria toxin A to ablate Clara cells in the adult lung. Epithelial regeneration and peribronchiolar fibrosis were assessed after acute and chronic Clara cell depletion. Measurements and Main Results: Acute Clara cell ablation caused squamous metaplasia of ciliated cells and induced proliferation of residual progenitor cells. Ciliated cells in the bronchioles and pro-surfactant protein C-expressingcells in the bronchiolar alveolar duct junctions did not proliferate. Epithelial cell proliferation occurred at multiple sites along the airways and was not selectively associated with regions around neuroepithelial bodies. Chronic Clara cell depletion resulted in ineffective repair and caused peribronchiolar fibrosis. Conclusions: Colocalization of proliferation and cell type-specific markers demonstrate that Clara cells are critical airway progenitor cells. Continuous depletion of Clara cells resulted in persistent squamous metaplasia, lack of normal reepithelialization, and peribronchiolar fibrosis. Induction of proliferation in subepithelial fibroblasts supports the concept that chronic epithelial depletion caused peribronchiolar fibrosis.


Defranco E.A.,University of Cincinnati | Defranco E.A.,Perinatal Institute | Lewis D.F.,University of South Alabama | Odibo A.O.,Washington University in St. Louis
American Journal of Obstetrics and Gynecology | Year: 2013

Objective: Our objective was to systematically review the current medical literature to assess the accuracy of the combination of fetal fibronectin (fFN) plus ultrasound assessment of cervical length (CL) as screening tools for preterm labor and prediction of preterm birth (PTB), and to compare this to the traditional clinical method of digital cervical examination. Study Design: We searched PubMed and Cochrane databases without date restriction using the key words "fibronectin" and "cervical length," limited to human studies published in English. In all, 85 studies were identified and supplemented by 1 additional study found through bibliographic search. Results: Nine studies reported the association between fFN positivity plus CL measurement with PTB in women presenting with symptomatic uterine contractions. We conducted an analytic review of the sensitivity, specificity, positive predictive value, and negative predictive value of fFN plus CL for PTB. Further metaanalysis was not performed due to study heterogeneity, especially with respect to the range of gestational ages and variations in cutoff values for the diagnosis of short cervix. Although the clinical diagnostic methodology of preterm labor diagnosis by documenting uterine contractions plus cervical change is currently standard practice, a newer approach combining fFN and CL screening results in a higher sensitivity and positive predictive value for PTB risk while maintaining high negative predictive value. Conclusion: We conclude that this combined screening approach yields useful information regarding short-term risks that can be used to guide acute management, and effectively identifies a population at low risk in whom expensive and potentially dangerous interventions could be avoided. © 2013 Mosby, Inc.

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