Hypercholesterolemia and Lymphatic Defects: The Chicken or the Egg?

Lymphatic vessels are necessary for maintaining tissue fluid balance, trafficking of immune cells, and transport of dietary lipids. Growing evidence suggest that lymphatic functions are limited under hypercholesterolemic conditions, which is closely related to atherosclerotic development involving the coronary and other large arteries. Indeed, ablation of lymphatic systems by Chy-mutation as well as depletion of lymphangiogenic factors, including vascular endothelial growth factor-C and -D, in mice perturbs lipoprotein composition to augment hypercholesterolemia. Several investigations have reported that periarterial microlymphatics were attracted by atheroma-derived lymphangiogenic factors, which facilitated lymphatic invasion into the intima of atherosclerotic lesions, thereby modifying immune cell trafficking. In contrast to the lipomodulatory and immunomodulatory roles of the lymphatic systems, the critical drivers of lymphangiogenesis and the details of lymphatic insults under hypercholesterolemic conditions have not been fully elucidated. Interestingly, cholesterol-lowering trials enable hypercholesterolemic prevention of lymphatic drainage in mice; however, a causal relationship between hypercholesterolemia and lymphatic defects remains elusive. In this review, the contribution of aberrant lymphangiogenesis and lymphatic cholesterol transport to hypercholesterolemic atherosclerosis was highlighted. The causal relationship between hypercholesterolemia and lymphatic insults as well as the current achievements in the field were discussed

Two Case Reports of Successful Withdrawal of Mycofenolate Mofetil After Living Donor Lobar Lung Transplantation

Background: Lung transplantation cases have immunosuppression maintained using a calcineurin inhibitor, anti-metabolites, and steroid. Case Report: We report 2 clinical cases in which anti-metabolites (mycophenolate mofetil) were successfully withdrawn after living donor lobar lung transplantation by monitoring immune function using the ImmuKnow® assay. In the first case, a 43-year-old woman underwent living donor lobar lung transplantation for pulmonary alveolar proteinosis. Two healthy relatives donated a lower lobe each. Immunosuppression was maintained using tacrolimus, mycophenolate mofetil, and steroid. Six months posttransplantation, she developed invasive pulmonary aspergillosis. During anti-fungal treatment, we withdrew mycophenolate mofetil and tacrolimus trough levels were kept around 8 ng/mL. Despite the resulting low-level immunosuppression, the ImmuKnow assay showed immune function to be in the moderate range with tacrolimus and steroid alone, encouraging us to maintain this strategy to avoid recurrence of invasive pulmonary aspergillosis. In the second case, a 24-year-old man underwent living donor lobar lung transplantation for cystic fibrosis. Two healthy relatives donated a lower lobe each. Immunosuppression was maintained using tacrolimus, mycophenolate mofetil, and steroid. Five months posttransplantation, he developed persistent Pseudomonas aeruginosa pneumonia derived from the paranasal sinuses. Under ImmuKnow assay monitoring, mycophenolate mofetil was withdrawn, but immune function was maintained within the moderate range using tacrolimus and steroid alone. Discussion: Respiratory function in both cases was maintained; no findings of bronchiolitis obliterans syndrome were noted during this period. To the best of our knowledge, no reports have described successful anti-metabolite withdrawal in lung transplantation with ImmuKnow monitoring. Immune evaluation by ImmuKnow could offer a useful method to monitor and control immune status, particularly among recipients susceptible to infection, revealing that moderate immune function could be maintained using tacrolimus and steroid in living donor lobar lung transplantation

Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer

Schematic diagrams of the signal cascade of EGF-induced DPD expression of EGFR-mutated type cells. TF, transcription factor; Mit A, mithramycin A. (JPG 130 kb

Surgical treatment for therapy-related pectoral hematoma: report of a case and review of published reports

A 96-year-old man with a rapidly growing right chest wall mass was referred to our department for further treatment. Enhanced chest computed tomography showed a huge pectoral hematoma (12×6 cm) in the right thorax. He was on oral antiplatelet medication, but no abnormalities in clotting ability were detected. Because the hematoma was enlarging and painful, it was evacuated surgically and hemostasis achieved around the pectoral branches of the thoraco-acromial artery. His postoperative course was uneventful with no evidence of subcutaneous fluid retention. Surgical hemostasis and hematoma evacuation of this pectoral hematoma might be effective as one treatment method

Successful treatment of mycotic thoracic aortic aneurysm in collaboration with cardiovascular and general thoracic surgeons

We report a rare case of ruptured mycotic thoracic aortic aneurysm that required almost one month for correct diagnosis. A 71-year-old woman who had hemoptysis for several weeks was initially suspected to have lung cancer based on several examinations, including fluorine-18 fluorodeoxyglucose-positron emission tomography. However, contrast-enhanced computed tomography revealed a ruptured mycotic thoracic aortic aneurysm in the lower lobe of the left lung. She underwent emergency surgery carried out collaboratively by cardiovascular and general thoracic surgeons. En bloc resection of the aneurysm with the left lower lobe and in situ graft replacement of the descending aorta were performed successfully, although left lower lobectomy was difficult due to the insufficient segmentation of the upper and lower lobes and strong adherence of the aneurysm to the left lung. The clinical course was uneventful. The reason for survival for one month was thought to be that the rupture was covered by the lung. Because the resection of the lung is often difficult in cases in which the aneurysmal rupture shows extensive lung invasion, collaboration with cardiovascular and general thoracic surgeons is important

Surgical resection of a pulmonary artery pseudoaneurysm after middle lobectomy: Report of a case

A case of surgical resection of a pulmonary artery pseudoaneurysm after middle lobectomy is reported. A 76-year-old man with lung cancer, interstitial pulmonary fibrosis, and pneumoconiosis was referred for surgical resection. Right middle lobectomy with lymph node dissection was successfully performed. Postoperatively, the patient did well until a sudden high fever developed on postoperative day eight. Antibiotic therapy was started for suspected acute pneumonia, but the low-grade fever did not improve. Contrast-enhanced computed tomography showed a bronchopleural fistula that caused a pulmonary artery pseudoaneurysm. Right lower lobectomy via posterolateral thoracotomy was performed to resect the pseudoaneurysm. The pulmonary artery stump was sutured by monofilament unabsorbable stiches. The bronchus stump was sutured interruptedly with a pedicle of intercostal muscles. The patient’s postoperative course following repeat thoracotomy was complicated, including exacerbation of interstitial pneumonia and tracheostomy. He is still in hospital, and weaning off the mechanical ventilator is being attempted

Isolation and characterization of a thermophilic, obligately anaerobic and heterotrophic marine Chloroflexi bacterium from a Chloroflexi dominated microbial community associated with a Japanese shallow hydrothermal system, and proposal for Thermomarinilinea lacunofontalis gen. nov., sp. nov.

A novel marine thermophilic and heterotrophic Anaerolineae bacterium in the phylum Chloroflexi, strain SW7T, was isolated from an in situ colonization system deployed in the main hydrothermal vent of the Taketomi submarine hot spring field located on the southern part of Yaeyama Archipelago, Japan. The microbial community associated with the hydrothermal vent was predominated by thermophilic heterotrophs such as Thermococcaceae and Anaerolineae, and the next dominant population was thermophilic sulfur oxidizers. Both aerobic and anaerobic hydrogenotrophs including methanogens were detected as minor populations. During the culture-dependent viable count analysis in this study, an Anaerolineae strain SW7T was isolated from an enrichment culture at a high dilution rate. Strain SW7T was an obligately anaerobic heterotroph grew with fermentation, and non-motile thin rods 3.5-16.5 μm in length and 0.2 μm in width constituting multicellular filament. Growth was observed between 37-65 ℃ (optimum 60℃), pH 5.5-7.3 (optimum pH 6.0), 0.5-3.5% (w/v) NaCl concentration (optimum 1.0%). Based on physiological and phylogenetic features of a new isolate, we propose a new species representing a novel genus Thermomarinilinea: the type strain of Thermomarinilinea lacunofontalis sp. nov., is SW7T (= JCM15506T = KCTC5908T)

Immune function in a patient with aspergillosis after lung transplantation: Case Report

We report a case that was successfully treated invasive pulmonary aspergillosis after living donor lobar lung transplantationand monitored patients\u27 immune function with ImmuKnow® assay. A 43-year-old woman underwent living donor lobar lungtransplantation for pulmonary alveolar proteinosis. Two healthy her relatives donated each lower lobe. Six months after transplantation,she was diagnosed as invasive pulmonary aspergillosis (IPA). During the anti-fungal treatment, one immunosuppressantwas withdrawn and the trough level of calcineurin inhibitor was reduced to the minimum. Despite of such a lowimmunosuppressive status, Immuknow® assay showed that immune function was maintained in the moderate range, whichencouraged us to keep this strategy for IPA. Immune evaluation by Immuknow® is useful method for monitoring and controllingpatients\u27 immune status especially in the infected condition, which revealed moderate immune level could be maintained withonly two immunosuppressant drugs in the patient after recovery from IPA

Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice

Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema