Characteristic scapular and rib changes on chest radiographs of children with ADA-deficiency SCIDS in the first year of life

Manson, David; Diamond, Lauren; Oudjhane, Kamaldine; Hussain, Faisal Bin; Roifman, Chaim M.; Grunebaum, Eyal

doi:10.1007/s00247-012-2564-2

Cited by 40 publications

(23 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, it is known that during pediatric development, the ribcage becomes more elliptical, as the (anterior-posterior) depth of the ribcage reduces relative to the (medial-lateral) breadth [24,[51][52][53]. Further, various deformities that commonly arise and progress during childhood, such as scoliosis and thanatophoric dysplasia, are known to cause alterations to the ribcage geometry [23,27,[54][55][56][57]. The current model could be useful for tracking these pediatric rib shape pathologies over time, and especially for the development of countermeasures such as braces [23,58].…”

Section: Futurementioning

confidence: 99%

Characterization of the Centroidal Geometry of Human Ribs

Kindig

Kent

2013

Journal of Biomechanical Engineering

View full text Add to dashboard Cite

While a number of studies have quantified overall ribcage morphology (breadth, depth, kyphosis/lordosis) and rib cross-sectional geometry in humans, few studies have characterized the centroidal geometry of individual ribs. In this study, a novel model is introduced to describe the centroidal path of a rib (i.e., the sequence of centroids connecting adjacent cross-sections) in terms of several physically-meaningful and intuitive geometric parameters. Surface reconstructions of rib levels 2-10 from 16 adult male cadavers (aged 31-75 years) were first extracted from CT scans, and the centroidal path was calculated in 3D for each rib using a custom numerical method. The projection of the centroidal path onto the plane of best fit (i.e., the "in-plane" centroidal path) was then modeled using two geometric primitives (a circle and a semiellipse) connected to give C1 continuity. Two additional parameters were used to describe the deviation of the centroidal path from this plane; further, the radius of curvature was calculated at various points along the rib length. This model was fit to each of the 144 extracted ribs, and average trends in rib size and shape with rib level were reported. In general, upper ribs (levels 2-5) had centroidal paths which were closer to circular, while lower ribs (levels 6-10) tended to be more elliptical; further the centroidal curvature at the posterior extremity was less pronounced for lower ribs. Lower ribs also tended to exhibit larger deviations from the best-fit plane. The rib dimensions and trends with subject stature were found to be consistent with findings previously reported in the literature. This model addresses a critical need in the biomechanics literature for the accurate characterization of rib geometry, and can be extended to a larger population as a simple and accurate way to represent the centroidal shape of human ribs.

show abstract

Section: Futurementioning

confidence: 99%

Characterization of the Centroidal Geometry of Human Ribs

Kindig

Kent

2013

Journal of Biomechanical Engineering

View full text Add to dashboard Cite

show abstract

“…ADA-deficient patients often present myeloid dysplasia features and bone marrow hypocellularity [64]. Manson et al showed that unusual chondroosseous findings could be seen in patients with ADA deficiency and these anomalies would be resolved during 6–12 months of ADA enzyme replacement therapy when adenosine levels are back to normal [65]. ATP as a Ca 2+ modulator was found to maintain proteoglycan values close to native tissue and increase collagen synthesis and functional properties of engineered cartilage by increasing Ca 2+ oscillations in monolayer-cultured chondrocytes [66].…”

Section: Adenosine Signalingmentioning

confidence: 99%

The Signaling Pathways Involved in Chondrocyte Differentiation and Hypertrophic Differentiation

Dong

2016

Stem Cells International

118

View full text Add to dashboard Cite

Chondrocytes communicate with each other mainly via diffusible signals rather than direct cell-to-cell contact. The chondrogenic differentiation of mesenchymal stem cells (MSCs) is well regulated by the interactions of varieties of growth factors, cytokines, and signaling molecules. A number of critical signaling molecules have been identified to regulate the differentiation of chondrocyte from mesenchymal progenitor cells to their terminal maturation of hypertrophic chondrocytes, including bone morphogenetic proteins (BMPs), SRY-related high-mobility group-box gene 9 (Sox9), parathyroid hormone-related peptide (PTHrP), Indian hedgehog (Ihh), fibroblast growth factor receptor 3 (FGFR3), and β-catenin. Except for these molecules, other factors such as adenosine, O2 tension, and reactive oxygen species (ROS) also have a vital role in cartilage formation and chondrocyte maturation. Here, we outlined the complex transcriptional network and the function of key factors in this network that determine and regulate the genetic program of chondrogenesis and chondrocyte differentiation.

show abstract

“…T, B and Natural Killer (NK) cells dysfunction is often present in ADA-deficient patients in infancy. In addition, patients may suffer from alveolar proteinosis [8], diverse neuro-developmental abnormalities [9] as well as bone and cartilage malformations [10]. Since the mid-1980, weekly injections of polyethylene glycol-modified bovine ADA (PEG-ADA) have been used to remove the toxic purine metabolites, improve T and B cell functions and correct for some of the non-immunologic abnormalities [11].…”

Section: Main Textmentioning

confidence: 99%

Gene therapy for primary immune deficiencies: a Canadian perspective

Tailor²,

Grunebaum

2017

Allergy Asthma Clin Immunol

Self Cite

View full text Add to dashboard Cite

The use of gene therapy (GT) for the treatment of primary immune deficiencies (PID) including severe combined immune deficiency (SCID) has progressed significantly in the recent years. In particular, long-term studies have shown that adenosine deaminase (ADA) gene delivery into ADA-deficient hematopoietic stem cells that are then transplanted into the patients corrects the abnormal function of the ADA enzyme, which leads to immune reconstitution. In contrast, the outcome was disappointing for patients with X-linked SCID, Wiskott–Aldrich syndrome and chronic granulomatous disease who received GT followed by autologous gene corrected transplantations, as many developed hematological malignancies. The malignancies were attributed to the predilection of the viruses used for gene delivery to integrated at oncogenic areas. The availability of safer and more efficient self-inactivating lentiviruses for gene delivery has reignited the interest in GT for many PID that are now in various stages of pre-clinical studies and clinical trials. Moreover, advances in early diagnosis of PID and gene editing technology coupled with enhanced abilities to generate and manipulate stem cells ex vivo are expected to further contribute to the benefit of GT for PID. Here we review the past, the present and the future of GT for PID, with particular emphasis on the Canadian perspective.

show abstract

Characteristic scapular and rib changes on chest radiographs of children with ADA-deficiency SCIDS in the first year of life

Abstract: Characteristic and reversible scapular and rib changes in the correct clinical setting should suggest an early diagnosis of ADA deficiency, prompting appropriate diagnostic and therapeutic measures.

Cited by 40 publications

References 5 publications

Characterization of the Centroidal Geometry of Human Ribs

Characterization of the Centroidal Geometry of Human Ribs

The Signaling Pathways Involved in Chondrocyte Differentiation and Hypertrophic Differentiation

Gene therapy for primary immune deficiencies: a Canadian perspective

Contact Info

Product

Resources

About