Shinsaku Ueda

Bone Marrow-Derived Progenitor Cells Are Important for Lung Repair after Lipopolysaccharide-Induced Lung Injury

Tissue repair often occurs in organs damaged by an inflammatory response. Inflammatory stimuli induce a rapid and massive release of inflammatory cells including neutrophils from the bone marrow. Recently, many studies suggested that bone marrow cells have the potential to differentiate into a variety of cell types. However, whether inflammatory stimuli induce release of bone marrow-derived progenitor cells (BMPCs), or how much impact the suppression of BMPCs has on the injured organ is not clear. Here we show that LPS, a component of Gram-negative bacterial cell walls, in the lung airways, induces a rapid mobilization of BMPCs into the circulation in mice. BMPCs accumulate within the inflammatory site and differentiate to become endothelial and epithelial cells. Moreover, the suppression of BMPCs by sublethal irradiation before intrapulmonary LPS leads to disruption of tissue structure and emphysema-like changes. Reconstitution of the bone marrow prevents these changes. These data suggest that BMPCs are important and required for lung repair after LPS-induced lung injury.

Bone-marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema

All‐trans retinoic acid (ATRA) is known to reverse the anatomic and physiologic signs of pulmonary emphysema. However, the origin of the progenitor cells involved in this lung regeneration remains unclear. Recently, it was shown that bone marrow could be the source of progenitor cells for several cell types. Mice with elastase‐induced emphysema were treated with ATRA, granulocyte colony‐stimulating factor (G‐CSF), or a combination of both. ATRA or G‐CSF promoted lung regeneration and increased bone marrow‐derived cell (BMC) numbers in alveoli. Combined treatment of both had an additive effect, which indicated that BMC mobilization might be important in lung regeneration.

The impact of a large-scale natural disaster on patients with chronic obstructive pulmonary disease: The aftermath of the 2011 Great East Japan Earthquake

BACKGROUND A large-scale natural disaster may exacerbate chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD). The aftermath of a natural disaster can include poor access to medication, medical equipment, and medical supplies. Little is known about the impact on patients with COPD. METHODS A retrospective cohort study was conducted at a regional medical center in Ishinomaki, the area affected most severely by the Great East Japan Earthquake in 2011. The study was performed 6 months after the disaster. The characteristics, clinical courses, and outcomes of COPD patients hospitalized after emergency visits during the study period were investigated and compared. RESULTS One hundred patients (112 episodes) were identified. Within a few days after the disaster, patients undergoing oxygen therapy at home came to the hospital to receive oxygen. In the subacute phase (from the third to the fifth week), the number of hospitalizations due to COPD exacerbations was significantly increased compared to the numbers observed before the earthquake (p<0.05). On admission, COPD patients reported significantly reduced participation in the activities of daily living (ADLs) after as compared to before the disaster. The incidence of cases of exacerbated COPD normalized 6 weeks after the earthquake. CONCLUSIONS The large-scale natural disaster that hit Japan in 2011 had a serious negative impact on the clinical outcomes of COPD patients in the disaster-affected area.

Effects of rewarming on nuclear factor-κb and interleukin 8 expression in cold-preserved alveolar epithelial cells

Background. Nuclear factor-&kgr;B (NF-&kgr;B) and interleukin (IL)-8 play important roles in the pathophysiology of acute lung injury after lung transplantation. Because alveolar epithelium is one of the most important sites at which IL-8 production takes place after reperfusion of donor lungs, we examined the effects of cold/rewarming on NF-&kgr;B and IL-8 expression in alveolar epithelial cells. Methods. A549 cells were preserved at 4°C for 5 hr and then rewarmed for up to 20 hr. NF-&kgr;B was analyzed by electrophoretic mobility shift assay. IL-8 mRNA expression was examined by reverse transcription-polymerase chain reaction. IL-8 concentration in the cell culture medium after rewarming was measured by enzyme-linked immunosorbent assay. Results. NF-&kgr;B was increased in the nuclear extracts as early as 30 min after rewarming. There was a marked increase in the IL-8 mRNA expression at 1 and 3 hr after rewarming. IL-8 concentration in the cell culture medium was progressively increased during 20 hr following rewarming. The cell culture medium inhibited apoptosis of neutrophils significantly. The cold/rewarming-induced IL-8 production was reduced to approximately 50% by introducing an antisense oligonucleotide for the p65 subunit of NF-&kgr;B and by treatment with N-acetyl-leucinyl-leucinyl-norleucinal and pyrrolidine dithiocarbamate. The effect of dexamethasone treatment was dose dependent (reduced to approximately 30% at 10−5 M dexamethasone). Conclusions. Our results indicate that rewarming of cold-preserved alveolar epithelial cells itself may be an important initiator of the inflammatory cascades, including NF-&kgr;B activation and IL-8 release. Inhibition of NF-&kgr;B would be worth trying to control unnecessary IL-8 production and the inflammatory response in the donor lungs.

Delayed cardiac rupture occurring two months after blunt chest trauma

We describe a rare case of successful repair of delayed cardiac rupture due to blunt chest trauma; the cardiac rupture occurred 74 days after the trauma. A 75-year-old woman with a history of blunt chest trauma that caused multiple rib fractures underwent an emergent thoracotomy due to left hemothorax. A coin-sized pericardial defect and cardiac rupture on the left ventricle was found to be close to a fractured rib, which was thought to have damaged the myocardium and thus induced timedependent myocardial degeneration. The cardiac rupture and the pericardial defect did not induce life-threatening cardiac tamponade; however, the cardiac rupture did induce hemothorax, which could be successfully treated.

One-Year Overview of Deep Vein Thrombosis Prevalence in the Ishinomaki Area Since the Great East Japan Earthquake

After the Great East-Japan Earthquake, the prevalence of deep vein thrombosis (DVT) in disaster shelters in Ishinomaki (Pacific coast, Miyagi, Japan) was found much higher than that ever reported in Japan. In Ishinomaki, twelve patients were found to have pulmonary thromboembolism for one month since the earthquake and DVT was found in 10 of those patients. The calf DVT was examined using ultrasonography in the shelters (from March to July 2011) and in temporary emergency housings (from August to December 2011). Calf DVT was found in 190 of 701 evacuees. DVT prevalence was higher in the tsunami-flooded shelters (34.2%) than in that in the non-flooded shelters (19.1%). This indicated that deteriorated and crowded condition in the tsunami-flooded shelters might induce thrombogenesis in calf veins. Therefore, evacuees were recommended to leave tsunami-flooded areas. DVT prevalence in the shelters was gradually reduced, however, that was still higher in the temporary emergency housings (8.9%) than in the non-disaster area in Japan (2.2% in Yokohama city). The risk of calf DVT in the temporary emergency housings was increased because of reduced blood flow in the calf veins caused by immobility. The residents of the housings were required to be physically active to avoid calf DVT. (English translation of Jpn J Phlebol 2013; 24: 380-384).

Superoxide possibly produced in endothelial cells mediates the neutrophil-induced lung injury

BACKGROUND The mechanism by which stimulated neutrophils (polymorphonuclear leukocytes [PMNs]) damage pulmonary vascular endothelium was investigated. METHODS The ability of unstimulated and mechanically stimulated PMNs to adhere to pulmonary endothelial cells and, thereby, alter pulmonary vascular permeability was tested. Each series was conducted on 6 rats. To stimulate PMNs, they were agitated gently in a glass vial for 10 seconds. RESULTS Perfusing lungs with the stimulated PMNs elicited a fivefold increase in permeability compared with lungs perfused with the unstimulated cells. This increase in permeability was blocked completely by preincubation of stimulated PMNs with CD18 monoclonal antibody. This increase in permeability was also blocked completely by superoxide dismutase (SOD) or the xanthine oxidase (XO) inhibitor allopurinol. Pulmonary vascular hemodynamics were unaffected by any treatment protocol. The accumulation of stimulated PMNs within the lungs was not inhibited by SOD but was partially blocked by allopurinol. CONCLUSIONS These findings suggest that stimulated PMN-induced increases in pulmonary vascular filtration resulted from endothelial cell injury caused by superoxide anion possibly generated by XO, exclusively present in the endothelial cells.

Chest injuries and the 2011 Great East Japan Earthquake

BACKGROUND Chest injuries caused during a major earthquake remain unclear. We have described profiles of patients with chest injuries who were diagnosed and treated at the area that was most affected by the Great East Japan Earthquake in 2011. METHODS We retrospectively reviewed medical records of 3938 patients who were transferred to the Japanese Red Cross Ishinomaki Hospital during the first week after the earthquake (March 11-17). In total, 77 patients were declared dead on arrival at the hospital. Of the remaining 3861 patients, 42 (1.1%) sustained chest injuries. Diagnosis of the chest injury was based on results of physical examination, chest radiography, and computed tomography. RESULTS Chest injury was diagnosed in 42 patients, including 22 men and 20 women (age range, 21-99 years). The most common cause of injury was tsunami (n=21), followed by falls (n=9), and traffic accidents (n=1), although this information was missing in 11 cases. The most common type of chest injury was superficial trauma such as laceration and contusion (n=37). Only 5 patients had rib fractures with intrathoracic damages such as pneumothorax (n=3), hemothorax (n=1), and aspiration (n=1). CONCLUSIONS The number of patients with chest injury was surprisingly small. Most patients did not require hospitalization. The small number of survivors with serious chest injuries can most likely be explained by the tsunami caused by the earthquake.

Ultrasound cardiography examinations detect victims’ long-term realized and potential consequences after major disasters: a case-control study

BackgroundAn increase in cardiovascular diseases has been reported following major disasters. Previous work has shown that ultrasonographic findings from ultrasound cardiography examination (UCG) increased until the 44th month after the tsunami caused by the Great East Japan Earthquake. The present study conducted UCG among victims in the tsunami disaster area and investigated the frequency of disaster-related cardiovascular diseases and changes over time until the 55th month after the disaster.MethodsThe subjects were residents of temporary housing complexes and neighboring housing in Watari-gun, Miyagi Prefecture, Japan. There were 207 subjects in the 18th month, 125 in the 30th month, 121 in the 44th month, and 106 in the 55th month after the disaster. Data were collected through UCG and self-report questionnaire.ResultsSignificant changes were observed among subjects with clinical findings from the UCG, which increased over the study period—from 42.0 to 60.8, 72.7, and 73.6% beginning in the 18th month after the disaster (p < 0.0001).ConclusionsIt is possible that the UCG can become a useful examination to visualize the potential impact of a major disaster on the cardiac function of victims. Victims with clinical findings continued increasing not only during the acute phase after a disaster but also in the long term. We therefore need to keep this in mind, and note that it is important to establish a support system to control cardiovascular diseases from the early stage of disaster.Trial registrationUMIN; ID000029802. R000034050. 2 November 2017.

The utility of on‐site ultrasound screening in population at high risk for deep venous thrombosis in temporary housing after the great East Japan Earthquake

To evaluate the diagnostic performance of ultrasonography for screening of a population at risk for deep vein thrombosis (DVT) in a post‐disaster setting.