21 results found
Tatham KC, O'Dea KP, Romano R, et al., 2018, Intravascular donor monocytes play a central role in lung transplant ischaemia-reperfusion injury, Thorax, Vol: 73, Pages: 350-360, ISSN: 1468-3296
Rationale Primary graft dysfunction in lung transplant recipients derives from the initial, largely leukocyte-dependent, ischaemia-reperfusion injury. Intravascular lung-marginated monocytes have been shown to play key roles in experimental acute lung injury, but their contribution to lung ischaemia-reperfusion injury post transplantation is unknown.Objective To define the role of donor intravascular monocytes in lung transplant-related acute lung injury and primary graft dysfunction.Methods Isolated perfused C57BL/6 murine lungs were subjected to warm ischaemia (2 hours) and reperfusion (2 hours) under normoxic conditions. Monocyte retention, activation phenotype and the effects of their depletion by intravenous clodronate-liposome treatment on lung inflammation and injury were determined. In human donor lung transplant samples, the presence and activation phenotype of monocytic cells (low side scatter, 27E10+, CD14+, HLA-DR+, CCR2+) were evaluated by flow cytometry and compared with post-implantation lung function.Results In mouse lungs following ischaemia-reperfusion, substantial numbers of lung-marginated monocytes remained within the pulmonary microvasculature, with reduced L-selectin and increased CD86 expression indicating their activation. Monocyte depletion resulted in reductions in lung wet:dry ratios, bronchoalveolar lavage fluid protein, and perfusate levels of RAGE, MIP-2 and KC, while monocyte repletion resulted in a partial restoration of the injury. In human lungs, correlations were observed between pre-implantation donor monocyte numbers/their CD86 and TREM-1 expression and post-implantation lung dysfunction at 48 and 72 hours.Conclusions These results indicate that lung-marginated intravascular monocytes are retained as a ‘passenger’ leukocyte population during lung transplantation, and play a key role in the development of transplant-associated ischaemia-reperfusion injury.
Wilson MR, Wakabayashi K, Bertok S, et al., 2017, Inhibition of TNF receptor p55 by a domain antibody attenuates the initial phase of acid-induced lung injury in mice, Frontiers in Immunology, Vol: 8, ISSN: 1664-3224
Background: Tumor necrosis factor-α (TNF) is strongly implicated in the development ofacute respiratory distress syndrome (ARDS), but its potential as a therapeutic target has beenhampered by its complex biology. TNF signals through two receptors, p55 and p75, whichplay differential roles in pulmonary edema formation during ARDS. We have recentlyshown that inhibition of p55 by a novel domain antibody (dAb™) attenuated ventilator36induced lung injury. In the current study we explored the efficacy of this antibody in mousemodels of acid-induced lung injury, to investigate the longer consequences of treatment.Methods: We employed two acid-induced injury models, an acute ventilated model and aresolving spontaneously breathing model. C57BL/6 mice were pretreated intratracheally orintranasally with p55-targeting dAb or non-targeting ‘dummy’ dAb, 1 or 4 hours before acidinstillation.Results: Acid instillation in the dummy dAb group caused hypoxemia, increased respiratorysystem elastance, pulmonary inflammation and edema in both the ventilated and resolvingmodels. Pretreatment with p55-targeting dAb significantly attenuated physiological markersof ARDS in both models. p55-targeting dAb also attenuated pulmonary inflammation in theventilated model, with signs that altered cytokine production and leukocyte recruitmentpersisted beyond the very acute phase.Conclusions: These results demonstrate that the p55-targeting dAb attenuates lung injury andedema formation in models of ARDS induced by acid aspiration, with protection from asingle dose lasting up to 24 hours. Together with our previous data, the current study lends support towards the clinical targeting of p55 for patients with, or at risk of ARDS.
Tatham KC, O'Dea KP, Romana R, et al., 2016, Retention And Activation Of Donor Vascular Monocytes In Transplanted Lungs Suggests A Central Role In Primary Graft Dysfunction, American Thoracic Society Conference 2016
Tatham KC, O'Dea KP, Romano R, et al., 2016, Retention And Activation Of Donor Vascular Monocytes In Transplanted Lungs Suggests A Central Role In Primary Graft Dysfunction, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Fletcher ME, Boshier PR, Wakabayashi K, et al., 2015, Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 308, Pages: L1274-L1285, ISSN: 1040-0605
Oxidant-mediated tissue injury is key to the pathogenesis of acute lung injury. Glutathione-S-transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of glutathione with toxic oxidant compounds and are associated with acute and chronic inflammatory lung diseases. We hypothesized that attenuation of cellular GST enzymes would augment intracellular oxidative and metabolic stress and induce lung cell injury. Treatment of murine lung epithelial cells with GST inhibitors, ethacrynic acid (EA), and caffeic acid compromised lung epithelial cell viability in a concentration-dependent manner. These inhibitors also potentiated cell injury induced by hydrogen peroxide (H2O2), tert-butyl-hydroperoxide, and hypoxia and reoxygenation (HR). SiRNA-mediated attenuation of GST-π but not GST-μ expression reduced cell viability and significantly enhanced stress (H2O2/HR)-induced injury. GST inhibitors also induced intracellular oxidative stress (measured by dihydrorhodamine 123 and dichlorofluorescein fluorescence), caused alterations in overall intracellular redox status (as evidenced by NAD+/NADH ratios), and increased protein carbonyl formation. Furthermore, the antioxidant N-acetylcysteine completely prevented EA-induced oxidative stress and cytotoxicity. Whereas EA had no effect on mitochondrial energetics, it significantly altered cellular metabolic profile. To explore the physiological impact of these cellular events, we used an ex vivo mouse-isolated perfused lung model. Supplementation of perfusate with EA markedly affected lung mechanics and significantly increased lung permeability. The results of our combined genetic, pharmacological, and metabolic studies on multiple platforms suggest the importance of GST enzymes, specifically GST-π, in the cellular and whole lung response to acute oxidative and metabolic stress. These may have important clinical implications.
Tatham KC, O'Dea KP, Wakabayashi K, et al., 2015, The role of ex vivo lung perfusion in lung transplantation., J Intensive Care Soc, Vol: 16, Pages: 58-63, ISSN: 1751-1437
Whilst lung transplantation is a viable solution for end-stage lung disease, donor shortages, donor lung inflammation and perioperative lung injury remain major limitations. Ex vivo lung perfusion has emerged as the next frontier in lung transplantation to address and overcome these limitations, with multicentre clinical trials ongoing in the UK, rest of Europe and North America. Our research seeks to identify the poorly understood cellular and molecular mechanisms of primary graft dysfunction through the development of an isolated perfused lung model of transplantation and investigation of the role of pulmonary inflammation in this paradigm.
Ohmori T, Shiota N, Haramo A, et al., 2015, Post-operative cardiac arrest induced by co-administration of amiodarone and dexmedetomidine: a case report., J Intensive Care, Vol: 3, ISSN: 2052-0492
We firstly report a postoperative hemodialysis patient who was co-administered with amiodarone and dexmedetomidine and developed severe bradycardia followed by cardiac arrest. A 79-year-old male patient underwent an amputation of the right lower extremity. The electrocardiogram of the patient showed a complete right bundle branch block with left anterior fascicular block before the anesthesia, and paroxysmal atrial tachycardia over 200 beats/min lasting 15 min was observed during surgery. After admission to the intensive care unit, the intensivist and the consultant cardiologist decided to treat tachycardia using amiodarone. The initial dosing of amiodarone and the maintenance infusion succeeded to decrease the heart rate. Approximately 2 h and a half after the start of dexmedetomidine infusion for sedation, the heart rate gradually declined and severe bradycardia suddenly followed by cardiac arrest was observed. Resuscitation was promptly initiated and the patient regained sinus rhythm without delay. In retrospective analysis, the monitoring record of the electrocardiogram revealed the marked atrioventricular conduction abnormalities. This is the first case report concerning a cardiac arrest induced by amiodarone and dexmedetomidine.
Wakabayashi K, Wilson MR, Tatham KC, et al., 2014, Volutrauma, but not Atelectrauma, Induces Systemic Cytokine Production by Lung-Marginated Monocytes, Critical Care Medicine, Vol: 42, Pages: e49-e57, ISSN: 0090-3493
Objectives: Ventilator-induced lung injury has substantive impact on mortality of patients with acute respiratory distress syndrome. Although low tidal volume ventilation has been shown to reduce mortality, clinical benefits of open-lung strategy are controversial. In this study, we investigated the impact of two distinct forms of ventilator-induced lung injury, i.e., volutrauma and atelectrauma, on the progression of lung injury and inflammation, in particular alveolar and systemic cytokine production.Design: Ex vivo study.Setting: University research laboratory.Subjects: C57BL/6 mice.Interventions: Isolated, buffer-perfused lungs were allocated to one of three ventilatory protocols for 3 hours: control group received low tidal volume (7 mL/kg) with positive end-expiratory pressure (5 cm H2O) and regular sustained inflation; high-stretch group received high tidal volume (30–32 mL/kg) with positive end-expiratory pressure (3 cm H2O) and sustained inflation; and atelectasis group received the same tidal volume as control but neither positive end-expiratory pressure nor sustained inflation.Measurements and Main Results: Both injurious ventilatory protocols developed comparable levels of physiological injury and pulmonary edema, measured by respiratory system mechanics and lavage fluid protein. High-stretch induced marked increases in proinflammatory cytokines in perfusate and lung lavage fluid, compared to control. In contrast, atelectasis had no effect on perfusate cytokines compared to control but did induce some up-regulation of lavage cytokines. Depletion of monocytes marginated within the lung microvasculature, achieved by pretreating mice with IV liposome-encapsulated clodronate, significantly attenuated perfusate cytokine levels, especially tumor necrosis factor, in the high-stretch, but not atelectasis group.Conclusions: Volutrauma (high-stretch), but not atelectrauma (atelectasis), directly activates monocytes within the pulm
Donaldson H, Tatham K, Odea K, et al., 2014, Subclinical endotoxaemia enhances lung ischaemia-reperfusion injury, Winter Meeting of the Anaesthetic-Research-Society (ARS), Publisher: OXFORD UNIV PRESS, Pages: 184P-185P, ISSN: 0007-0912
Wakabayashi K, Wilson M, Tatham K, et al., 2013, High-stretch, but not atelectasis, causes systemic cytokine release by lung-marginated monocytes, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Tatham K, Donaldson H, O'Dea K, et al., 2013, Marginated monocytes play a central role in lung ischaemia-reperfusion injury in mice: Implications for lung transplantation, EUROPEAN RESPIRATORY JOURNAL, Vol: 42, ISSN: 0903-1936
Wakabayashi K, Wilson MR, Patel BV, et al., 2013, Inhibition Of TNF Receptor p55 By A Domain Antibody Attenuates Acid-Induced Lung Injury In Mice, American Thoracic Society
RationaleTumor necrosis factor (TNF) is strongly implicated in the evolution of acute lung injury (ALI), but its potential as a therapeutic target has been hampered by its complex biology. TNF signals through two cell surface receptors, p55 and p75, which play differential roles in ALI, with p55 promoting injury while p75 opposes this. We have recently shown that selective p55 blockade using novel domain antibody technology attenuates ventilator-induced lung injury (VILI) in mice. To further translate these findings to the bedside, we explored the potential for selective blockade of p55 in a clinically relevant mouse model of acid-induced ALI.MethodsMale C57BL6 mice were pretreated with intranasal administration of either specific domain antibody to p55 (dAb) or non-specific control domain antibody (‘dummy’). Four hours later, the mice were either instrumented for analysis without further instillation (i.e. baseline) or intratracheally challenged with hydrochloric acid (0.1M, 75μl) via an oro-tracheal tube to induce ALI. All acid-challenged animals were instrumented for analysis at 24 hours after acid instillation. Analysis consisted of mice being anesthetized, tracheostomized, and mechanically ventilated in order to evaluate PaO2/FiO2 ratio and respiratory mechanics. The left lung was taken for determining wet/dry ratio and a lunglavage sample was taken from the right lung to measure protein levels and neutrophil counts.ResultsHydrochloric acid instillation in the dummy group resulted in severe ALI, represented by hypoxemia, elastance increase, pulmonary edema and inflammation (Table 1). These mice were also visually very sick, showing considerably reduced locomotion and responsiveness. In contrast, pretreatment with p55 dAb dramatically improved the clinical symptoms, along with significant attenuation in all the physiological markers of lung injury. However, the dAb treatment did not significantly attenuate lung neutrophil recruitment represented b
Dorr AD, Wilson MR, Wakabayashi K, et al., 2011, Sources of alveolar soluble TNF receptors during acute lung injury of different etiologies, JOURNAL OF APPLIED PHYSIOLOGY, Vol: 111, Pages: 177-184, ISSN: 8750-7587
Wakabayashi K, Wilson MR, O'Dea KP, et al., 2011, Atelectasis Induces Chemokine Upregulation And Lung Injury In The Isolated Perfused Mouse Lung, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Wakabayashi K, Wilson MR, O'Dea KP, et al., 2010, COMPARISON OF HIGH-STRETCH VERSUS ATELECTASIS IN THE PATHOPHYSIOLOGY OF VENTILATOR-INDUCED LUNG INJURY USING THE MOUSE ISOLATED PERFUSED LUNG, British-Thoracic-Society-Winter-Meeting 2010, Publisher: B M J PUBLISHING GROUP, Pages: A49-A50, ISSN: 0040-6376
Wakabayashi K, Wilson MR, O'Dea KP, et al., 2009, ROLE OF INTRAVASCULAR LEUCOCYTES IN VENTILATOR-INDUCED LUNG INJURY IN THE ISOLATED PERFUSED MOUSE LUNG, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A48-A49, ISSN: 0040-6376
O'Dea KP, Wilson MR, Dokpesi JO, et al., 2009, Mobilization and Margination of Bone Marrow Gr-1(high) Monocytes during Subclinical Endotoxemia Predisposes the Lungs toward Acute Injury, JOURNAL OF IMMUNOLOGY, Vol: 182, Pages: 1155-1166, ISSN: 0022-1767
Dorr AD, Wilson MR, Wakabayashi K, et al., 2009, Injurious Ventilation and Intratracheal Lipopolysaccharide Increase Soluble TNF Receptors in the Alveoli Via Distinct Mechanisms, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Dorr AD, Wilson MR, Wakabayashi K, et al., 2008, INJURIOUS VENTILATION AND INTRATRACHEAL LIPOPOLYSACCHARIDE INCREASE SOLUBLE TUMOUR NECROSIS FACTOR RECEPTORS IN THE ALVEOLI VIA TWO DISTINCT MECHANISMS, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A71-A71, ISSN: 0040-6376
Wakabayashi K, Ohya T, Arii S, et al., 2006, A Case of Giant Cell Fibroblastoma, Journal of the Japanese Society of Pediatric Surgeons, Vol: 42, Pages: 258-262, ISSN: 0288-609X
We encountered a 2-year-old boy with a giant cell fibroblastoma (GCF). A small mass, sized 5mm in diameter was noticed at the right chest wall by the parents at 1 year of age. He had been observed for 1 year at a nearby hospital with questionable diagnosis of lymphangioma. The mass gradually enlarged and the patient was referred to us. On admission, the mass was 5.5cm in diameter, fixed tightly to the skin. It was covered by normal skin and no fluctuation or tenderness was seen. Ultrasonography showed a mixed pattern; however, CAT scan showed homogenous, low-density mass with a weak enhanced effect. No calcification was seen. T1 weighted MRI demonstrated homogenous, low-intensity signal and the T2 weighted image showed a variable high-intensity signal. Heterogenous enhancement was observed. These imaging studies suggested a neurogenic tumor with a mucinous component or myxoid liposarcoma. The en-bloc resection was perfomed with a part of the skin and fascia. Pathological examination revealed spindle-shaped cells, multinucleated giant cells, a sinusoid-like space with a mucinous component, and a positive resulf for CD34, so GCF was concluded. GCF is a rare mesenchymal neoplasm, mostly developed in boys in the first decade of life. It often presents as a painless, slow-growing subcutaneous mass, especially in the trunk and the upper limbs. The local recurrence rate is up to 50%; however no metastasis was previously reported.
Inoue Y, Ohya T, Wakabayashi K, et al., 2003, Benefits of the VEID (Vein Entry Indicator Device) in the Field of Pediatric Suregery, Journal of the Japanese Society of Pediatric Surgeons, Vol: 39, Pages: 988-991, ISSN: 0288-609X
Purpose: The VEID (vein entry indicator device) is a small pressure sensor for indicating venous entry. This paper describes our experience of using the VEID in the field of pediatric surgery. Material and Methods: We used a VEID for taking blood samples from 158 patients, venous access for 23 patients and central venous catheter insertion for five patients. A survey of seven doctors using VEID was performed. Results: The VEID worked well for taking blood samples and venous access. On the other hand, it failed to work for four out of five patients for central venous catheter insertion. Three doctors felt that the VEID was very useful, four felt it was useful, and no one felt it was useless. However, four doctors thought that the VEID needes some modification. Conclusion: The VEID is not an essential device, but it could provide confidence to physicians. Furthermore, it reduces the uneasiness or tension of the patients at the time of procedure.
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