Autophagy is a process of lysosomal self-degradation that helps to maintain the homeostatic balance between the synthesis, degradation and recycling of cellular proteins and organelles. Autophagy does not simply function as the machinery for supplying amino acids in response to energy demands, it is an adaptive pathway of cytoprotection against cellular stressors, including starvation, reactive oxygen species (ROS), endoplasmic reticulum (ER) stress and microbial infection. Accordingly, autophagy is considered to be the mediator of a variety of cellular processes and cell fates, including cell survival and death, cellular senescence and immune responses. Due to the organ-specific role of gas exchange, various cell types within the lungs are serially exposed to a diverse array of cellular stressors, and growing evidence has revealed the crucial involvement of autophagy in the pathogenic processes underlying pulmonary diseases. We herein review recent findings regarding the role of autophagy in cellular processes and cell fates and summarize the role that autophagy appears to play in the pathogenesis of pulmonary diseases.
Objective To study the clinical efficacy of catheter ablation for paroxysmal atrial fibrillation (AF) in patients with a permanent pacemaker (PM) for sick sinus syndrome (SSS). Methods Our prospectively established database of patients who underwent circumferential pulmonary vein (PV) ablation for paroxysmal AF was retrospectively reviewed. A total of 41 patients with a permanent PM for the treatment of SSS (SSS+PM group) and 123 age- and gender-matched control subjects (on a 1: 3 basis) without SSS or a permanent PM (no-SSS+no-PM group) were included in this study. AF recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30 seconds beyond three months after catheter ablation in the absence of any antiarrhythmic treatment. Results During a mean follow-up period of 18.3±10.6 months (range 3-30 months), 50 patients (30.5%) developed recurrence of AF. The recurrence rate was higher in the SSS+PM group than in the no-SSS+no-PM group (43.9% vs. 26.3%, p=0.011). A Cox regression analysis adjusted for age, valvular heart disease, left atrial (LA) diameter and PV isolation identified only SSS and the use of a PM together as an independent predictor of recurrence of AF (hazard ratio 2.02, 95% confidence interval 1.10-3.69, p=0.023). Conclusion Patients with a permanent PM for SSS are at an increased risk of recurrence of AF after catheter ablation.
A 31-year-old woman with primary mediastinal large B-cell lymphoma refractory to conventional chemotherapy was treated with high-dose chemotherapy containing cyclophosphamide (CY). Subsequently, she was treated with auto peripheral blood stem cell transplantation. Although a complete remission was obtained, heart failure developed two months later. Echocardiography showed an impaired systolic function with pericardial effusion. A biopsy of the endomyocardial region from the left ventricle demonstrated spotty myocardial hemorrhage and myocardial fibrosis with disruption and aggregation of mitochondrial cristae. Based on these findings, CY-induced cardiotoxicity was diagnosed. The patient was treated with conventional therapy for heart failure, which required approximately one year to improve her condition.
A 42-year-old female with body weight loss, finger tremors and ocular discomfort was diagnosed with Graves' disease complicated with ophthalmopathy. Thiamazole therapy rapidly improved her hyperthyroidism. However, she was admitted to our hospital because her eye symptoms acutely deteriorated over a period of two weeks. She had ocular immotility, exposure keratitis, conjunctival edema, severe proptosis and visual impairment with a high titer of serum thyroid-stimulating antibody (TSAb). Methylprednisolone pulse therapy at a dose of 500 mg/day improved her eye symptoms. Although the mechanism of the progression of Graves' ophthalmopathy has not yet been elucidated, special attention should be paid to the occurrence of ophthalmopathy even after the initiation of thiamazole therapy.
False positive radioiodine uptake following thyroidectomy for differentiated thyroid cancer has been reported in some cases. A 42-year-old woman was referred for ablative radioiodine treatment six weeks after undergoing total thyroidectomy for papillary thyroid carcinoma. Posttherapeutic I-131 scintigraphy showed an intense hot spot in the left pelvis. Pelvic computed tomography (CT) revealed a benign left ovarian mass such as a functional cyst. After menstruation, ultrasonographic imaging demonstrated a shrunken ovarian mass. Therefore, we diagnosed the patient with a functional cyst that was influenced by hormonal fluctuation. It is believed that this is the first case of false-positive radioiodine uptake in a functional ovarian cyst.
We herein report a rare case of pulmonary mucosa-associated lymphoid tissue (p-MALT) lymphoma with multiple cystic lesions. A previously healthy 58-year-old Japanese woman visited our hospital for an evaluation of abnormal chest computed tomography (CT) findings. Chest CT revealed multiple cystic lesions in both lungs, and she was diagnosed as having p-MALT lymphoma based on the pathological findings. The patient had no underlying autoimmune diseases. She has not received any chemotherapy and has been stable for two years. This case suggests that, although rare, the possibility of p-MALT lymphoma should be considered in patients with multiple cystic lung diseases.
One-third of lung cancer patients present with life-threatening central airway obstruction (CAO). Two elderly patients were referred to our institution with symptoms caused by CAO. In each case, thoracic computed tomography and a bronchoscopic examination revealed a tumor obstructing the central airway. The tumors were resected endoscopically, and the patients' respiratory and performance status remarkably improved. Both patients were diagnosed with an advanced stage of lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations. They received gefitinib monotherapy, with partial responses sustained for more than 12 months. Combination therapy with endoscopic tumor resection and gefitinib is beneficial in patients with EGFR-mutant lung cancer and CAO.
We herein report two cases of combined pulmonary fibrosis and emphysema (CPFE), whose histological patterns of lung pathology could not be categorized into any subset of idiopathic interstitial pneumonias(IIPs). Case 1 was a 62-year-old man, who presented with dyspnea on exertion and cough. Case 2 was a 51-year-old man with a dry cough. The CT findings of both cases fit the definition of CPFE. Surgical lung biopsies of both patients revealed alveolar septal widening due to collagen deposition, with emphysema and respiratory bronchiolitis mainly in the subpleural parenchyma. These cases suggest that the fibrosis of CPFE includes smoking-related interstitial fibrosis other than the known histological patterns of IIPs.
A 36-year-old woman presented with hemolytic anemia without a reticulocyte response 38 days after delivery. A marked reduction in erythroid cells and an increase in macrophages with active hemophagocytosis were noted in the bone marrow. While conventional Coombs' tests were negative, the level of red blood cell (RBC)-bound immunoglobulin G (IgG) was increased. The patient was diagnosed with primary Sjögren syndrome (pSS) based on her symptoms, positive anti-SS-A antibodies, Coombs-negative autoimmune hemolytic anemia and pure red cell aplasia associated with RBC-bound IgG and hemophagocytosis. The unique presentation was considered to be a consequence of immunological derangement associated with pSS, pregnancy and delivery.
Pseudoperipheral palsy can be caused by cerebral cortical infarctions; however, it is rarely caused by lacunar infarctions, including those in the posterior limb of the internal capsule. Meanwhile, the somatotopic localization of the corticospinal tract in the posterior limb of the internal capsule remains unknown. We herein report the case of an 81-year-old Japanese woman who presented with a left hand drop. Brain magnetic resonance imaging revealed an acute infarction as the causative lesion at the inferior level of the anteromedial portion of the posterior limb of the right internal capsule. This case report indicates the topography of hand fibers in the internal capsule.
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by progressive lymphocyte infiltration of the exocrine glands. Overt or latent renal tubular acidosis (RTA) is a common extraglandular manifestation of pSS.Vitamin D deficiency is associated with autoimmune disorders; however, the potential correlation between pSS and vitamin D deficiency is rarely discussed. The current patient presented with distal RTA, hypocalcemia, and hypophosphatemia that were found to be secondary to both vitamin D deficiency and pSS. In patients diagnosed with both distal RTA and vitamin D deficiency, clinicians should consider autoimmune diseases such as pSS, as a possible underlying etiology.
Streptococcus pneumoniae is a rare pathogen of sepsis in patients with antithyroid drug-induced agranulocytosis. We herein describe a case of antithyroid drug-induced agranulocytosis complicated by pneumococcal sepsis and upper airway obstruction. A 27-year-old woman who was previously prescribed methimazole for nine months presented with a four-day history of a sore throat. She nearly choked and was diagnosed with febrile agranulocytosis. She was successfully treated with intubation, intravenous antibiotics and granulocyte colony-stimulating factor. Her blood cultures yielded S. pneumoniae. Emergency airway management, treatment of sepsis and the administration of granulocyte colony-stimulating factor can improve the clinical course of antithyroid drug-induced pneumococcal sepsis in patients with airway obstruction.
Peripheral mycotic aneurysm is a rare complication of infective endocarditis. We herein report the case of a 61-year-old man with a mycotic aneurysm in the left brachial artery, that appeared during treatment with antibiotics against infective endocarditis caused by Streptococcus sanguinis. After confirming the collateral blood flow on arteriography, we resected the aneurysm and performed valvuloplasty, annuloplasty and coronary artery bypass grafting. The patient has been in good condition without complications, such as motor dysfunction or neuropathy.
Hyperimmunoglobulin E syndrome (HIES) is sporadically triggered by de novo genetic mutations of the signal transducer and activator of transcription 3 (STAT3). Dialysis patients frequently exhibit HIES-like symptoms including elevated IgE levels and recurrent bacterial infections. We herein report the case of a 74-year-old man on hemodialysis (HD) who developed marked IgE elevation and multiple subcutaneous cold Staphylococcus aureus abscesses. We are the first to report that a dialysis patient presented with HIES-like symptoms without the characteristic facies or bone and connective tissue abnormalities. A STAT3 gene analysis was conducted as part of the differential diagnosis.