Bronchial artery revascularization restores peribronchial tissue oxygenation after lung transplantation.

With the interruption of the bronchial arteries after lung transplantation, nutritive support is dependent on collateral flow by the pulmonary arteries with desaturated venous blood. Consequently, oxygen deficiency of the peribronchial and dependent lung tissue may occur. Using a canine model for left lung transplantation, we investigated hypoxic peribronchial tissue after conventional lung transplantation and demonstrated restitution of tissue oxygenation after transplantation with bronchial artery revascularization (BAR) (BAR group: Po2 120.4 +/- 28.7 mm Hg; control group Po2 6.8 +/- 2.8; p < 0.001). BAR in lung transplantation protects peribronchial tissue of the transplanted graft from hypoxia in the early phase after reperfusion.     

Primary amelanotic melanoma of the breast: combating a rare cancer

Background

Malignant melanoma is the foremost cause of metastasis to the breast from extramammary solid neoplasm. However primary melanoma of the breast is a distinct rarity. Primary melanoma involves the skin and less commonly the glandular parenchyma of the breast.

Method

We herein describe a case of primary amelanotic melanoma of the breast parenchyma in a 32-year-old female managed with a combination of surgery, adjuvant radiotherapy and immunotherapy.

Conclusion

This case report aims to increase awareness of unusual neoplasms of the breast which might require a different surgical and adjuvant therapeutic approach.     

PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection

Type 2 inflammation is associated with epithelial cell responses, including goblet cell hyperplasia, that promote worm expulsion during intestinal helminth infection. How these epithelial responses are regulated remains incompletely understood. Here, we show that mice deficient in the prostaglandin D₂ (PGD₂) receptor CRTH2 and mice with CRTH2 deficiency only in nonhematopoietic cells exhibited enhanced worm clearance and intestinal goblet cell hyperplasia following infection with the helminth Nippostrongylus brasiliensis. Small intestinal stem, goblet, and tuft cells expressed CRTH2. CRTH2-deficient small intestinal organoids showed enhanced budding and terminal differentiation to the goblet cell lineage. During helminth infection or in organoids, PGD₂ and CRTH2 down-regulated intestinal epithelial Il13ra1 expression and reversed Type 2 cytokine–mediated suppression of epithelial cell proliferation and promotion of goblet cell accumulation. These data show that the PGD₂–CRTH2 pathway negatively regulates the Type 2 cytokine–driven epithelial program, revealing a mechanism that can temper the highly inflammatory effects of the anti-helminth response.     

The effects of adenocaine (adenosine and lidocaine) on early post-resuscitation cardiac and neurological dysfunction in a porcine model of cardiac arrest

Aim

Return of spontaneous circulation (ROSC) elicits ischaemia/reperfusion injury and myocardial dysfunction. The combination of adenosine and lidocaine (AL, adenocaine) has been shown to (1) inhibit neutrophil inflammatory activation and (2) improve left ventricular function after ischaemia. We hypothesized that resuscitation with adenocaine during early moments of cardiopulmonary resuscitation (CPR) attenuates leucocyte oxidant generation and myocardial dysfunction.

Methods

Pigs were randomized to: (1) sham (n = 7), (2) cardiac arrest (CA; n = 16), or 3) cardiac arrest + adenocaine (CA + AL; n = 12). After 7 min of electrically induced ventricular fibrillation, start of CPR was followed by infusion of saline (CA) or adenocaine (CA + AL) for 6 min. Haemodynamics, cardiodynamics (pressure–volume loops) and leucocyte superoxide anion generation were assessed. Neurological function was evaluated after 24 h by histology and neurological deficit score (0 = normal; 500 = brain dead).

Results

Rate of ROSC was comparable between groups: CA group 11/16 and CA + AL group 7/12 p = 0.57). Cardiac index transiently increased after ROSC in both groups. Left ventricular dysfunction demonstrated by a rightward shift of the intercept of end-systolic pressure–volume relations in CA was avoided in the CA + AL group. Leucocyte superoxide anion generation 2 h after ROSC was significantly attenuated in the CA + AL group compared to the CA group. Neurological deficit scores [CA: median: 17.5(IQR:0–75) and CA + AL: 35(IQR:15–150)] and histopathological damage were comparable in both groups (p = 0.37).

Conclusion

Infusion of adenocaine during early resuscitation from CA significantly improved early post-resuscitation cardiac function and attenuated leucocyte superoxide anion generation, without a change in post-ROSC neurological function. (IACUC protocol number 023-2009).     

Differentiation and functional regulation of human fetal NK cells

The human fetal immune system is naturally exposed to maternal allogeneic cells, maternal antibodies, and pathogens. As such, it is faced with a considerable challenge with respect to the balance between immune reactivity and tolerance. Here, we show that fetal natural killer (NK) cells differentiate early in utero and are highly responsive to cytokines and antibody-mediated stimulation but respond poorly to HLA class I–negative target cells. Strikingly, expression of killer-cell immunoglobulin-like receptors (KIRs) did not educate fetal NK cells but rendered them hyporesponsive to target cells lacking HLA class I. In addition, fetal NK cells were highly susceptible to TGF-β–mediated suppression, and blocking of TGF-β signaling enhanced fetal NK cell responses to target cells. Our data demonstrate that KIR-mediated hyporesponsiveness and TGF-β–mediated suppression are major factors determining human fetal NK cell hyporesponsiveness to HLA class I–negative target cells and provide a potential mechanism for fetal-maternal tolerance in utero. Finally, our results provide a basis for understanding the role of fetal NK cells in pregnancy complications in which NK cells could be involved, for example, during in utero infections and anti-RhD–induced fetal anemia.     

Fast retrospectively triggered local pulse-wave velocity measurements in mice with CMR-microscopy using a radial trajectory

Background

The aortic pulse-wave velocity (PWV) is an important indicator of cardiovascular risk. In recent studies MRI methods have been developed to measure this parameter noninvasively in mice. Present techniques require additional hardware for cardiac and respiratory gating. In this work a robust self-gated measurement of the local PWV in mice without the need of triggering probes is proposed.

Methods

The local PWV of 6-months-old wild-type C57BL/6J mice (n=6) was measured in the abdominal aorta with a retrospectively triggered radial Phase Contrast (PC) MR sequence using the flow-area (QA) method. A navigator signal was extracted from the CMR data of highly asymmetric radial projections with short repetition time (TR=3 ms) and post-processed with high-pass and low-pass filters for retrospective cardiac and respiratory gating. The self-gating signal was used for a reconstruction of high-resolution Cine frames of the aortic motion. To assess the local PWV the volume flow Q and the cross-sectional area A of the aorta were determined. The results were compared with the values measured with a triggered Cartesian and an undersampled triggered radial PC-Cine sequence.

Results

In all examined animals a self-gating signal could be extracted and used for retrospective breath-gating and PC-Cine reconstruction. With the non-triggered measurement PWV values of 2.3±0.2 m/s were determined. These values are in agreement with those measured with the triggered Cartesian (2.4±0.2 m/s) and the triggered radial (2.3±0.2 m/s) measurement. Due to the strong robustness of the radial trajectory against undersampling an acceleration of more than two relative to the prospectively triggered Cartesian sampling could be achieved with the retrospective method.

Conclusion

With the radial flow-encoding sequence the extraction of a self-gating signal is feasible. The retrospective method enables a robust and fast measurement of the local PWV without the need of additional trigger hardware.     

Elevated frequency of gamma interferon-producing NK cells in healthy adults vaccinated against influenza virus

Recent studies indicate that innate immunity in influenza virus infection is an area of substantial importance for our understanding of influenza virus pathogenesis, yet our knowledge of the mechanisms controlling innate immunity remains limited. Further delineation of the roles of NK cells and innate immunity in viral infection may have important implications for the development of improved influenza virus vaccines. In this study, we evaluated the phenotype and function of NK and T lymphocytes, as well as influenza virus-specific immunoglobulin G production, prior to and following vaccination with the routinely administered trivalent influenza virus vaccine. We demonstrate influenza virus antigen-specific innate and adaptive cellular responses and evaluate changes in NK cell receptor expression over time. Our results demonstrate increased innate and adaptive cellular immune responses and show that NK cells are a significant source of gamma interferon (IFN-γ) following influenza virus vaccination. An increase in the frequency of IFN-γ-producing NK cells was observed in many subjects postvaccination. The subset distribution with respect to CD56^dim and CD56^bright NK cell subsets remained stable, as did the NK cell phenotype with respect to expression of cell surface activating and inhibitory receptors. These results may form the basis for further investigations of the role of NK cells in immunity to influenza.