TAK1 maintains the survival of immunoglobulin λ‐chain‐positive B cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135064/1/gtc12442-sup-0001-FigS1-S6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135064/2/gtc12442.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135064/3/gtc12442_am.pd

The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help

Germinal center (GC) B cells cycle between two states, the light zone (LZ) and the dark zone (DZ), and in the latter they proliferate and hypermutate their immunoglobulin genes. How this functional transition takes place is still controversial. In this study, we demonstrate that ablation of Foxo1 after GC development led to the loss of the DZ GC B cells and disruption of the GC architecture, which is consistent with recent studies. Mechanistically, even upon provision of adequate T cell help, Foxo1-deficient GC B cells showed less proliferative expansion than controls. Moreover, we found that the transcription factor BATF was transiently induced in LZ GC B cells in a Foxo1-dependent manner and that deletion of BATF similarly led to GC disruption. Thus, our results are consistent with a model where the switch from the LZ to the DZ is triggered after receipt of T cell help, and suggest that Foxo1-mediated BATF up-regulation is at least partly involved in this switch

Impact of chronic lung allograft dysfunction, especially restrictive allograft syndrome, on the survival after living-donor lobar lung transplantation compared with cadaveric lung transplantation in adults: a single-center experience

PURPOSE: The differences in chronic lung allograft dysfunction (CLAD) between living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT) remain unclear. We conducted this study to compare the impact of CLAD on the outcomes after LDLLT vs. CLT. METHODS: We conducted a retrospective review of the data of 97 recipients of bilateral lung transplantation, including 51 recipients of LDLLT and 46 recipients of CLT. RESULTS: The CLAD-free survival and overall survival after LDLLT were similar to those after CLT. CLAD and restrictive allograft syndrome (RAS), but not bronchiolitis obliterans syndrome (BOS), developed significantly later after LDLLT than after CLT (p = 0.015 and p = 0.035). Consequently, patients with CLAD and RAS, but not those with BOS, after LDLLT had a significantly better overall survival than those after CLT (p = 0.037 and p = 0.0006). Furthermore, after the diagnosis of CLAD, the survival of patients with RAS after LDLLT tended to be better than that after CLT (p = 0.083). CONCLUSION: CLAD, especially RAS, appears to develop later after LDLLT than after CLT and seems to have a lower impact on the overall survival after LDLLT than that after CLT

2006 ネンド コウガクブ シンニュウセイ オ タイショウ トシタ ボウサイ キョウイク ノ ジッシ ト ボウサイ イシキ チョウサ

本論文では，徳島大学工学部の2006 年度新入生を対象とした防災教育の実施と，同時に実施し たアンケート調査の結果から，学生の防災意識の現状を把握するとともに，徳島大学の防災教育のあ り方について検討を行った．アンケート調査の結果より，被災経験のある学生が多く存在するものの， 防災意識・知識が低く，防災訓練の経験に偏りが見られたこと，およびその重要性を認識できていな い傾向があることがわかった．一方，災害ボランティア活動に対して興味が持っている学生が多く， 災害時にボランティア活動に従事することが可能である，と答えた学生も多く見られた．災害時の 「自助・共助」を推進するためには，本学において防災教育を実施し，災害および防災に対する正し い知識と理解を深める必要があることを示した．This paper aims that recognition about Disaster prevention of the New Students entered the faculty of engineering the University of Tokushima in April, 2006. The authors used a questionnaire for investigation and analyzed it. As a result of having analyzed it, most of students cannot understand disaster prevention and more than half of them are single lives, but the students are interested in volunteer activity. By a disaster of the past, a youth is a lot dead next to an old man, too. The reason is because the students were crushed under furniture when an earthquake was generated a student lives in a simple building and a room is small. If students do volunteer activity of a disaster, it is very dangerous. The reason is because it leads to not only a primary disaster but also a second disaster. In other words, the students improve disaster prevention recognition and must understand disasters

Feasibility of lung transplantation from donors mechanically ventilated for prolonged periods

PURPOSE: When patients are mechanically ventilated for more than 5 days, they are usually declined as donors for lung transplantation (LTx); thus, the long-term outcomes of LTx from such donors remain unclear. We investigated the feasibility of LTx from donors that had been mechanically ventilated for prolonged periods. METHODS: The subjects of this retrospective comparative investigation were 31 recipients of LTx from donors who had been mechanically ventilated for RESULTS: The median duration of donor mechanical ventilation was 3 days in the short-term group and 8.5 days in the long-term group. However, other than the difference in the duration of donor ventilation, there were no significant differences in the clinical characteristics of the donors or recipients between the groups. The overall survival rate after LTx was comparable between the long-term group and short-term group (5-year survival rate, 66.6% vs. 75.2%). CONCLUSION: The potential inclusion of donors who have been on mechanical ventilation for more than 5 days could be a feasible strategy to alleviate donor organ shortage

Perioperative therapy for non-small cell lung cancer - Current status and future perspective -

　Lung cancer is the leading cause of cancer-related death. Surgery has been playing a pivotal role in the treatments with curative intent for non-small cell lung cancer (NSCLC). However, the outcome after surgery alone remains unsatisfactory. During the last two decades, several attempts have been made to improve the postoperative outcome. Metaanalysis demonstrated that adjuvant cisplatin-based chemotherapy achieved 4-5% of benefit in the 5-year survival as compared to surgery alone. Preoperative induction chemotherapy also yielded a 5% improvement of the 5-year survival rate, showing a similar efficacy with adjuvant chemotherapy. Induction chemoradiotherapy enhanced local control, whereas it was not associated with any survival benefit. Recently, the development of new drugs, such as tyrosine kinase inhibitors and immune checkpoint inhibitors, represents a major treatment advance for patients with lung cancer. Several attempts have been made to apply these drugs to perioperative treatments.　In this review, we sought to summarize the developments of perioperative therapy in the treatments of NSCLC, and discuss the future perspectives

Lung perfusion scintigraphy to detect chronic lung allograft dysfunction after living-donor lobar lung transplantation

Because chronic lung allograft dysfunction (CLAD) develops predominantly on one side after bilateral living-donor lobar lung transplantation (LDLLT), lung perfusion scintigraphy (Q-scinti) was expected to show a perfusion shift to the contralateral unaffected lung with the development of CLAD. Our study examined the potential usefulness of Q-scinti in the diagnosis of CLAD after bilateral LDLLT. We conducted a single-center retrospective cohort study of 58 recipients of bilateral LDLLT. The unilateral shift values on Q-scinti were calculated and compared between the CLAD group (N=27) and the non-CLAD group (N=31) from 5 years before to 5 years after the diagnosis of CLAD. The unilateral shift values in Q-scinti were significantly higher in the CLAD group than in the non-CLAD group from 5 years before the diagnosis of CLAD to 5 years after the diagnosis (P<0.05). The unilateral shift values in Q-scinti were significantly correlated with the percent baseline values of the forced expiratory volume in 1 s (P=0.0037), the total lung capacity (P=0.0028), and the forced vital capacity (P=0.00024) at the diagnosis of CLAD. In patients developing unilateral CLAD after bilateral LDLLT, Q-scinti showed a unilateral perfusion shift to the contralateral unaffected lung. Thus, Q-scinti appears to have the potential to predict unilateral CLAD after bilateral LDLLT

Right single lung transplantation using an inverted left donor lung: interposition of pericardial conduit for pulmonary venous anastomosis-a case report

BACKGROUND: Lung transplantation (LTx) is still limited by the shortage of suitable donor lungs. Developing flexible surgical procedures can help to increase the chances of LTx by unfolding recipient-to-donor matching options based on the pre-existing organ allocation concept. We report a case in which a successful left-to-right inverted LTx was completed using the interposition of a pericardial conduit for pulmonary venous anastomosis. CASE PRESENTATION: A left lung graft was offered to a 59-year-old male who had idiopathic pulmonary fibrosis with predominant damage in the right lung. He had been prescribed bed rest with constant oxygen inhalation through an oxymizer pendant and had been on the waiting list for 20 months. Considering the condition of the patient (LAS 34.3) and the scarcity of domestic organ offers, the patient was highly likely to be incapable of tolerating any additional waiting time for another donor organ if he was unable to accept the presently reported offer of a left lung. Eventually, we decided to transplant the left donor lung into the right thorax of the recipient. Because of the anterior-posterior position gap of the hilar structures, the cuff lengths of the pulmonary veins had to be adjusted. The patient did not develop any anastomotic complications after the transplantation. CONCLUSIONS: A left-to-right inverted LTx is technically feasible using an autologous pericardial conduit for pulmonary venous anastomosis in selected cases. This technique provides the potential benefit of resolving challenging situations in which surgeons must deal with a patient's urgency and the logistical limitations of organ allocation

Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory

One component of memory in the antibody system is long-lived memory B cells selected for the expression of somatically mutated, high-affinity antibodies in the T cell–dependent germinal center (GC) reaction. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. Using conditional Bcl6 ablation, we demonstrate that these cells are generated through proliferative expansion early after immunization in a T cell–dependent but GC-independent manner. They soon become resting and long-lived and display a novel distinct gene expression signature which distinguishes memory B cells from other classes of B cells. GC-independent memory B cells are later joined by somatically mutated GC descendants at roughly equal proportions and these two types of memory cells efficiently generate adoptive secondary antibody responses. Deletion of T follicular helper (Tfh) cells significantly reduces the generation of mutated, but not unmutated, memory cells early on in the response. Thus, B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One pathway is dedicated to the generation of high-affinity somatic antibody mutants, whereas the other preserves germ line antibody specificities and may prepare the organism for rapid responses to antigenic variants of the invading pathogen