Coronary ostium occlusion by coronary cusp displacement in Williams syndrome

Williams syndrome is a contiguous gene deletion syndrome resulting from a heterozygous deletion on chromosome 7q11.23, and is characterized by distinctive facial features and supravalvular aortic stenosis (SVAS). This syndrome rarely presents unpredictable cardiac death, and yet, as illustrated in the present case, it is still not possible to predict it, even on close monitoring. We herein describe the case of a 6‐year‐old Japanese girl with Williams syndrome, who had sudden cardiac collapse due to cardiac infarction after pharyngitis. Cardiac failure followed a critical course that did not respond to catecholamine support or heart rest with extracardiac mechanical support. Although marked coronary stenosis was not present, the left coronary cusp abnormally adhered to the aortic wall, which may synergistically cause coronary ostium occlusion with SVAS. Altered hemodynamic state, even that caused by the common cold, may lead to critical myocardial events in Williams syndrome with SVAS.     

Spleen Tyrosine Kinase Modulates Fibrous Airway Obliteration and Associated Lymphoid Neogenesis After Transplantation

Chronic lung allograft dysfunction, the major cause of death following lung transplantation, usually manifests as irreversible airflow obstruction associated with obliterative bronchiolitis (OB), a lesion characterized by chronic inflammation, lymphoid neogenesis, fibroproliferation and small airway obliteration. Spleen tyrosine kinase (Syk), a tyrosine kinase that regulates B cell function and innate immunity, has been implicated in the pathogenesis of chronic inflammation and tissue repair. This study evaluated the role of Syk in development of OB, using an intrapulmonary tracheal transplant model of OB with the conditional Syk‐knockout Syk^flox/flox//rosa26‐CreER^T2 mice and a Syk‐selective inhibitor, GSK2230413. BALB/c trachea allografts were transplanted into Syk‐knockout (Syk^del/del) mice or wild‐type C57BL/6 recipients treated with GSK2230413. At day 28, histological analysis revealed that in the Syk^del/del and GSK2230413‐treated C57BL/6 recipients, the graft lumen remained open compared with allografts transplanted into Syk‐expressing (Syk^flox/flox) and placebo control–treated C57BL/6 recipients. Immunofluorescence showed lymphoid neogenesis with distinct B and T cell zones in control mice. In contrast, lymphoid neogenesis was absent and few B or T cells were found in Syk^del/del and GSK2230413‐treated mice. These observations suggest that inhibition of Syk may be a potential therapeutic strategy for the management of OB following lung transplantation.     

Validation study of arm positions for evaluation of global spinal balance in EOS imaging

Background

The sagittal vertical axis (SVA) is important in the evaluation of spinal sagittal balance. Although the “fists-on-clavicles” (FOC) position has been widely used in radiographic examinations, it does not define shoulder flexion in detail. Meanwhile, in EOS imaging, the “hands-on-cheeks” (HOC) position is widely used but has not been well investigated. The purpose of this study was to investigate the relative usefulness of FOC and HOC in investigating SVA.

Materials and methods

Mean SVA was measured by EOS imaging using standing lateral radiographs of 34 volunteers in four different positions: relaxed (RLX), shoulder flexion at 90° with FOC (FOC90), elbows touching the trunk with FOC (FOCET), and HOC.

Results

The mean SVA was 2.0 ± 2.1 cm in RLX; ?1.4 ± 3.2 cm in FOC90; ?0.5 ± 3.0 cm in FOCET; and ?0.2 ± 2.9 cm in HOC. The negative shift from RLX was significantly greater in FOC90 than in FOCET (?3.4 ± 2.2 vs ?2.5 ± 2.4 cm; p = 0.0182). The negative shift from RLX in HOC was almost equal to that in FOCET; the difference was 0.3 cm (?2.2 ± 2.2 vs ?2.5 ± 2.4 cm; p = 0.2560).

Conclusion

FOC90 showed a negative SVA shift in comparison with FOCET. The difference in the mean SVA between HOC and FOCET was 0.3 cm, a clinically small difference.

     

Regulatory roles of mast cells in immune responses

Mast cells are important immune cells for host defense through activation of innate immunity (via toll-like receptors or complement receptors) and acquired immunity (via FcεRI). Conversely, mast cells also act as effector cells that exacerbate development of allergic or autoimmune disorders. Yet, several lines of evidence show that mast cells act as regulatory cells to suppress certain inflammatory diseases. Here, we review the mechanisms by which mast cells suppress diseases.     

Hypoxia augments MHC class I antigen presentation via facilitation of ERO1‐α‐mediated oxidative folding in murine tumor cells

To establish an effective cancer immunotherapy, it is crucial that cancer cells present a cancer‐specific antigen in a hypoxic area, a hallmark of the tumor microenvironment. Here, we show the impact of hypoxia on MHC class I antigen presentation in vitro and in vivo in murine tumors. Activation of antigen‐specific CTLs by tumor cells that had been pre‐incubated under a condition of hypoxia was enhanced compared with that by tumor cells pre‐incubated under a condition of normoxia. Cell surface expression of MHC class I‐peptide complex on the tumor cells was increased under a condition of hypoxia, thereby leading to higher susceptibility to specific CTLs. We show that the hypoxia‐inducible ER‐resident oxidase ERO1‐α plays an important role in the hypoxia‐induced augmentation of MHC class I‐peptide complex expression. ERO1‐α facilitated oxidative folding of MHC class I heavy chains, thereby resulting in the augmentation of cell surface expression of MHC class I‐peptide complex under hypoxic conditions. These results suggest that since the expression of MHC class I‐peptide complex is augmented in a hypoxic tumor microenvironment, strategies for inhibiting the function of regulatory T cells and myeloid‐derived suppressor cells and/or immunotherapy with immune checkpoint inhibitors are promising for improving cancer immunotherapy.