Usefulness of Silent MR Angiography for Intracranial Aneurysms Treated with a Flow-Diverter Device.

BACKGROUND AND PURPOSE: The flow-diverter device has been established as a treatment procedure for large unruptured intracranial aneurysms. The purpose of this study was to compare the usefulness of Silent MR angiography and time-of-flight MRA to assess the parent artery and the embolization state of the aneurysm after a flow-diverter placement. MATERIALS AND METHODS: Seventy-eight large, unruptured internal carotid aneurysms in 78 patients were the subjects of this study. After 6 months of treatment, they underwent follow-up digital subtraction angiography, Silent MRA, and TOF-MRA, performed simultaneously. All images were independently reviewed by 2 neurosurgeons and 1 radiologist and rated on a 4-point scale from 1 (not visible) to 4 (excellent) to evaluate the parent artery. The aneurysmal embolization status was assessed with 2 ratings: complete or incomplete occlusion. RESULTS: The mean scores of Silent MRA and TOF-MRA regarding the parent artery were 3.18 ± 0.72 and 2.31 ± 0.86, respectively, showing a significantly better score with Silent MRA (P < .01). In the assessment of the embolization of aneurysms on Silent MRA and TOF-MRA compared with DSA, the percentages of agreement were 91.0% and 80.8%, respectively. CONCLUSIONS: Silent MRA is superior for visualizing blood flow images inside flow-diverter devices compared with TOF-MRA. Furthermore, Silent MRA enables the assessment of aneurysmal embolization status. Silent MRA is useful for assessing the status of large and giant unruptured internal carotid aneurysms after flow-diverter placement.

Management of De Novo Mycobacterial Infection After Lung Transplantation Without Rifampicin: Case Series of a Single Institution.

BACKGROUND AND OBJECTIVES: To treat organ transplant patients with mycobacterial infection, physicians need to pay attention to interaction between drugs used against mycobacteria and immunosuppressants. The purpose of this report is to describe the clinical features of and treatment for mycobacterial infection in lung transplant (LTx) recipients. METHODS: To investigate the incidence, treatment, and outcome for mycobacterial infection, we retrospectively reviewed 100 LTx recipients in our program since 2000. RESULTS: Four recipients (4.0%) developed mycobacterial infection. Three recipients took tacrolimus, and 1 received cyclosporine with mycophenolate mofetil and a steroid for immunosuppression. Tuberculosis (TB) was isolated from 2 recipients, and non-tuberculous mycobacteriosis (NTM) was detected in the other 2. We treated the patients with levofloxacin + isoniazid + pyrazinamide + ethambutol (EB) for TB and clarithromycin (CLM) + EB for NTM to avoid interaction of calcineurin inhibitors (CNI: 8-10 ng/mL in trough level) with rifampicin (RFP). In treating the patients with NTM, we were able to maintain an adequate blood concentration of CNI by decreasing the dosage from one-half to one-quarter. All mycobacterial infections were controlled with treatment. In 1 patient with chronic obstructive pulmonary disease (COPD) infected with TB in the native lung, the forced expiratory volume in 1 second (FEV1) unexpectedly increased from 1890 mL before infection to 2320 mL possibly due to organization of the native lung. CONCLUSIONS: We were able to manage the mycobacterial infections using drugs other than RFP without any cases of acute rejection under adequate immunosuppression. Organization of the native lung with TB infection unexpectedly resulted in improvement of FEV1 in a COPD patient.

Sustained-Release Tacrolimus Stabilizes Decline of Forced Expiratory Volume in 1 Second Through Decreasing Fluctuation of Its Trough Blood Level.

BACKGROUND: Calcineurin inhibitors are a commonly used immunosuppressive drug and over 80% of lung transplant (LTx) recipients use tacrolimus. Sustained-release tacrolimus (SRT) was developed as a once-daily formulation, resulting in slower release and reduction in peak concentration compared with twice-daily immediate-release tacrolimus (IRT). Previous reports indicate that SRT may carry fewer side effects than IRT; however, the impact of SRT in bronchiolitis obliterans syndrome (BOS) after LTx is unclear. OBJECTIVE: Our study objective was to evaluate the effect of SRT in BOS after LTx. MATERIALS AND METHODS: We investigated the effect of SRT for BOS among 75 LTx recipients who were alive in 2017 in our LTx program. All analyses were carried out using student t test or F test. RESULTS: Thirty-five recipients took IRT, 32 recipients used SRT, 7 recipients used cyclosporine, and 1 patient who received bone marrow and a lung graft from the same donor did not use a calcineurin inhibitor. The most frequent reason for conversion of IRT to SRT was kidney dysfunction, followed by other IRT complications. Five recipients underwent conversion of IRT to SRT because of decline of forced expiratory volume in 1 second (FEV1) with fluctuation of the tacrolimus trough level. After induction of SRT, the fluctuation of the tacrolimus trough level was significantly reduced in 4 of 5 patients (P < .05). Before drug form conversion, the FEV1 in these 5 patients was significantly decreased; however, this exacerbation of FEV1 was attenuated after SRT induction (P < .05). CONCLUSION: SRT appeared to stabilize decline of FEV1 in patients with BOS possibly due to reducing the fluctuation of tacrolimus trough blood concentration.

Endobronchial Topical Amphotericin B Instillation for Pulmonary Chromomycosis After Lung Transplantation: A Case Report.

We report a very rare case of pulmonary chromomycosis caused by Scedosporium prolificans that developed after lung transplantation and was successfully treated with endobronchial topical amphotericin B instillation. The subject was a woman in her 50s with a history of bilateral lobar lung transplantation from living donors for idiopathic pulmonary hypertension. Eight years after the lung transplantation, chest radiography X-ray and computed tomography showed an abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary chromomycosis after S. prolificans was detected in the bronchial aspirate. Systemic antifungal treatment with itraconazole was ineffective. Therefore, we administered topical amphotericin B weekly via endobronchial instillation and replaced oral itraconazole with voriconazole. The endobronchial procedure was safe and tolerable. Bronchial obstruction improved after three 3 instillations. We continued topical amphotericin B instillation once every 3 months for 2 years, and the abnormal shadow nearly disappeared. This case report describes infection by S. prolificans, which rarely becomes an etiologic agent in lung transplant patients, and shows that endobronchial topical amphotericin B instillation is a therapeutic option when systemic antifungal treatment is ineffective.

Non-Contrast-Enhanced Silent Scan MR Angiography of Intracranial Anterior Circulation Aneurysms Treated with a Low-Profile Visualized Intraluminal Support Device.

BACKGROUND AND PURPOSE: The Low-Profile Visualized Intraluminal Support Device comprises a small-cell nitinol structure and a single-wire braided stent that provides greater metal coverage than previously reported intracranial stents, as well as assumed strong susceptibility artifacts. This study aimed to assess the benefits of non-contrast-enhanced MRA by using a Silent Scan (Silent MRA) for intracranial anterior circulation aneurysms treated with Low-Profile Visualized Intraluminal Support Device stents. MATERIALS AND METHODS: Thirty-one aneurysms treated with Low-Profile Visualized Intraluminal Support Device stents were assessed by using Silent MRA, 3D TOF-MRA, and x-ray DSA. The quality of MRA visualization of the reconstructed artery was graded on a 4-point scale from 1 (not visible) to 4 (excellent). Aneurysm occlusion status was evaluated by using a 2-grade scale (total occlusion/remnant [neck or aneurysm]). Weighted κ statistics were used to evaluate interobserver and intermodality agreement. RESULTS: The mean scores ± SDs for Silent MRA and 3D TOF-MRA were 3.16 ± 0.79 and 1.48 ± 0.67 (P < .05), respectively, with substantial interobserver agreement (κ = 0.66). The aneurysm occlusion rates of the 2-grade scale (total occlusion/remnant [neck or aneurysm]) were 69%/31% for DSA, 65%/35% for Silent MRA, and 92%/8% for 3D TOF-MRA, respectively. The intermodality agreements were 0.88 and 0.30 for DSA/Silent MRA and DSA/3D TOF-MRA, respectively. CONCLUSIONS: Silent MRA seems to be useful for visualizing intracranial anterior circulation aneurysms treated with Low-Profile Visualized Intraluminal Support Device stents.

Usefulness of Non-Contrast-Enhanced MR Angiography Using a Silent Scan for Follow-Up after Y-Configuration Stent-Assisted Coil Embolization for Basilar Tip Aneurysms.

BACKGROUND AND PURPOSE: Y-configuration stent-assisted coil embolization is used for treating wide-neck aneurysms. Noninvasive alternatives to x-ray DSA for follow-up after Y-configuration stent-assisted coil embolization treatment are required. This study aimed to assess the usefulness of non-contrast-enhanced MRA by using a Silent Scan (silent MRA) for follow-up after Y-configuration stent-assisted coil embolization for basilar tip aneurysms. MATERIALS AND METHODS: Seven patients treated with Y-configuration stent-assisted coil embolization for basilar tip aneurysms underwent silent MRA, 3D TOF-MRA, and DSA. Silent MRA and 3D TOF-MRA images were obtained during the same scan session on a 3T MR imaging system. Two neuroradiologists independently reviewed both types of MRA images and subjectively scored the flow in the stents on a scale of 1 (not visible) to 5 (nearly equal to DSA) by referring to the latest DSA image as a criterion standard. Furthermore, we evaluated the visualization of the neck remnant. RESULTS: In all patients, the 2 observers gave a higher score for the flow in the stents on silent MRA than on 3D TOF-MRA. The average score ± standard deviation was 4.07 ± 0.70 for silent MRA and 1.93 ± 0.80 (P < .05) for 3D TOF-MRA. Neck remnants were depicted by DSA in 5 patients. In silent MRA, neck remnants were depicted in 5 patients, and visualization was similar to DSA; however, in 3D TOF-MRA, neck remnants were depicted in only 1 patient. CONCLUSIONS: Silent MRA might be useful for follow-up after Y-configuration stent-assisted coil embolization.

Spleen Tyrosine Kinase Modulates Fibrous Airway Obliteration and Associated Lymphoid Neogenesis After Transplantation.

Chronic lung allograft dysfunction, the major cause of death following lung transplantation, usually manifests as irreversible airflow obstruction associated with obliterative bronchiolitis (OB), a lesion characterized by chronic inflammation, lymphoid neogenesis, fibroproliferation and small airway obliteration. Spleen tyrosine kinase (Syk), a tyrosine kinase that regulates B cell function and innate immunity, has been implicated in the pathogenesis of chronic inflammation and tissue repair. This study evaluated the role of Syk in development of OB, using an intrapulmonary tracheal transplant model of OB with the conditional Syk-knockout Syk(flox/flox) //rosa26-CreER(T2) mice and a Syk-selective inhibitor, GSK2230413. BALB/c trachea allografts were transplanted into Syk-knockout (Syk(del/del) ) mice or wild-type C57BL/6 recipients treated with GSK2230413. At day 28, histological analysis revealed that in the Syk(del/del) and GSK2230413-treated C57BL/6 recipients, the graft lumen remained open compared with allografts transplanted into Syk-expressing (Syk(flox/flox) ) and placebo control-treated C57BL/6 recipients. Immunofluorescence showed lymphoid neogenesis with distinct B and T cell zones in control mice. In contrast, lymphoid neogenesis was absent and few B or T cells were found in Syk(del/del) and GSK2230413-treated mice. These observations suggest that inhibition of Syk may be a potential therapeutic strategy for the management of OB following lung transplantation.

Impact of CLAD Phenotype on Survival After Lung Retransplantation: A Multicenter Study.

Chronic lung allograft dysfunction (CLAD) remains a major problem after lung transplantation with no definitive treatment except redo lung transplantation (re-LTx) in selected candidates. However, CLAD is not a homogeneous entity and different phenotypes exist. Therefore, we aimed to evaluate the effect of CLAD phenotypes on survival after re-LTx for CLAD. Patients who underwent re-LTx for respiratory failure secondary to CLAD in four LTx centers between 2003 and 2013 were included in this retrospective analysis. Bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD) were distinguished using pulmonary function, radiology and explant lung histopathology. Patient variables pre- and post-re-LTx were collected and analyzed. A total of 143 patients underwent re-LTx for CLAD resulting in 94 BOS (66%) and 49 rCLAD (34%) patients. Unadjusted and adjusted survival after re-LTx for rCLAD was worse compared to BOS (HR = 2.60, 1.59-4.24; p < 0.0001 and HR = 2.61, 1.51-4.51; p = 0.0006, respectively). Patients waiting at home prior to re-LTx experienced better survival compared to hospitalized patients (HR 0.40; 0.23-0.72; p = 0.0022). Patients with rCLAD redeveloped CLAD earlier and were more likely to redevelop rCLAD. Survival after re-LTx for rCLAD is worse compared to BOS. Consequently, re-LTx for rCLAD should be critically discussed, particularly when additional peri-operative risk factors are present.

Assessing Blood Flow in an Intracranial Stent: A Feasibility Study of MR Angiography Using a Silent Scan after Stent-Assisted Coil Embolization for Anterior Circulation Aneurysms.

BACKGROUND AND PURPOSE: Blood flow in an intracranial stent cannot be visualized with 3D time-of-flight MR angiography owing to magnetic susceptibility and radiofrequency shielding. As a novel follow-up tool after stent-assisted coil embolization, we applied MRA by using a Silent Scan algorithm that contains an ultrashort TE combined with an arterial spin-labeling technique (Silent MRA). The purpose of this study was to determine whether Silent MRA could visualize flow in an intracranial stent placed in the anterior circulation. MATERIALS AND METHODS: Nine patients treated with stent-assisted coil embolization for anterior circulation aneurysms underwent MRAs (Silent MRA and TOF MRA) and x-ray digital subtraction angiography. MRAs were performed in the same session on a 3T unit. Two neuroradiologists independently reviewed the MRA images and subjectively scored flow in a stent as 1 (not visible) to 4 (excellent) by referring to the latest x-ray digital subtraction angiography image as a criterion standard. RESULTS: Both observers gave MRA higher scores than TOF MRA for flow in a stent in all cases. The mean score for Silent MRA was 3.44 ± 0.53, and for TOF MRA, it was 1.44 ± 0.46 (P < .001). CONCLUSIONS: Silent MRA was able to visualize flow in an intracranial stent more effectively than TOF MRA. Silent MRA might be useful for follow-up imaging after stent-assisted coil embolization, though these study results may be only preliminary due to some limitations.

A simplified pull-through angioplasty technique without a snare device. A technical note.

The pull-through angioplasty technique allows stable wire tension and stabilization of the device during the procedure. In this technique, a guide wire is passed from one sheath to another, usually with the aid of a snare device. We describe the treatment of occlusive subclavian artery disease and lesion at the origin of the vertebral artery employing a brachiofemoral pull-through technique without using a snare device. In this technique, the guide wire is advanced from the femoral artery to the brachial artery. The guide wire is directly inserted into the sheath placed at the brachial artery. The brachial artery is compressed proximal to the point of sheath insertion to prevent bleeding. The sheath is extracted temporally and the guide wire is caught outside of the body. The sheath is then introduced again through the guide wire. We used the pull-through technique without a snare device in seven cases, and we were able to build the pull-through system in six of these cases without a snare device. This pull-through technique without a snare device is not difficult to use, and may reduce the time and cost of angioplasty procedures.

Lentivirus IL-10 gene therapy down-regulates IL-17 and attenuates mouse orthotopic lung allograft rejection.

The purpose of the study was to examine the effect of lentivirus-mediated IL-10 gene therapy to target lung allograft rejection in a mouse orthotopic left lung transplantation model. IL-10 may regulate posttransplant immunity mediated by IL-17. Lentivirus-mediated trans-airway luciferase gene transfer to the donor lung resulted in persistent luciferase activity up to 6 months posttransplant in the isograft (B6 to B6); luciferase activity decreased in minor-mismatched allograft lungs (B10 to B6) in association with moderate rejection. Fully MHC-mismatched allograft transplantation (BALB/c to B6) resulted in severe rejection and complete loss of luciferase activity. In minor-mismatched allografts, IL-10-encoding lentivirus gene therapy reduced the acute rejection score compared with the lentivirus-luciferase control at posttransplant day 28 (3.0 ± 0.6 vs. 2.0 ± 0.6 (mean ± SD); p = 0.025; n = 6/group). IL-10 gene therapy also significantly reduced gene expression of IL-17, IL-23, and retinoic acid-related orphan receptor (ROR)-γt without affecting levels of IL-12 and interferon-γ (IFN-γ). Cells expressing IL-17 were dramatically reduced in the allograft lung. In conclusion, lentivirus-mediated IL-10 gene therapy significantly reduced expression of IL-17 and other associated genes in the transplanted allograft lung and attenuated posttransplant immune responses after orthotopic lung transplantation.

Endovascular therapy of 500 small asymptomatic unruptured intracranial aneurysms.

BACKGROUND AND PURPOSE: Although the natural course of UIAs remains unclear, the risk of aneurysmal SAH due to small (<10 mm) asymptomatic UIAs is low. Endovascular therapy for UIAs has increased because of device development and the need for less invasive treatment. We report the results, safety, and efficacy of endovascular therapy of small asymptomatic UIAs. MATERIALS AND METHODS: A total of 457 patients with 500 small asymptomatic UIAs (maximum diameter < 10 mm) underwent endosaccular coil embolization at Juntendo University Hospital and affiliated hospitals. We retrospectively evaluated the technical feasibility, immediate and short-to-midterm follow-up anatomic results, procedure-related complications, and clinical outcomes. RESULTS: Endosaccular coil embolization was completed in 481 aneurysms (96.2%) and attempted in 19 (3.8%). Completed aneurysms were treated with the simple (39.5%), balloon-assisted (51.4%), and double-catheter (9.1%) techniques. Immediate angiographic outcomes were CO for 309 (64.2%) aneurysms, RN for 72 (15.0%), and RA for 100 (20.8%). Procedure-related complications occurred in 38 aneurysms (7.6%): 19 ischemic, 11 hemorrhagic, and 8 others. Permanent morbidity and mortality were 0.8% and 0.2%, respectively. Anatomic outcome of 427 aneurysms followed up for >6 months with conventional catheter or MR angiographies showed recanalization in 72 (16.9%) aneurysms, necessitating retreatment in 9.9% (mean, 31.4 months). No patients had aneurysmal SAH during the clinical follow-up period (mean, 34.7 months). CONCLUSIONS: In this series, endovascular therapy of small asymptomatic UIAs was highly feasible with low morbidity and mortality rates.

[Emergency anterior approach for decortication with right pneumonectomy in a patient with chronic expanding hematoma].

The patient was a 68 year-old woman who had a history of treatment of pulmonary tuberculosis 35 years ago. She has experienced dyspnea and hemosputa since several years ago and has been followed up as having chronic empyema. She was admitted to our hospital due to recent exacerbation of symptoms. X-ray films and computed tomography scans of the chest showed the right thoracic cavity to be totally filled with a mass and the shift of mediastinum to the left side. After several days from admission, she needed mechanical ventilation support due to dyspnea exacerbation. Emergency decortication with right pneumonectomy through median sternotomy with anterolateral incision was performed. Postoperative course was uneventful. Pathlogical diagnosis was chronic expanding hematoma.

[Management of surgical approach for intractable secondary spontaneous pneumothorax].

Secondary spontaneous pneumothorax (SSP) such as lymphangioleiomyomatosis (LAM), bronchiolitis obliterans (BO) is intractable or repeated the recurrence of pneumothorax. The most effective chemical pleurodesis for intractable pneumothorax is talc poudrage and so on that is associated with a reduction in the rate of pneumothorax recurrence. However, severe and broad pleural adhesion due to the pleural interventional procedures sometimes cause serious bleeding when the patients undergo lung transplantation. We must be considered for new approaches to these intractable secondary pneumothoraces which replaced traditional conservative and surgical approaches. We had proposed new 2 approaches of total pleural covering (TPC) and awake surgical intervention (ASI) for intractable pneumothorax. We applied the TPC modified with coverage of air leak points with polyglycolic acid (PGA) sheet to 5 patients with intractable bilateral pneumothorax to reduce the risk of excessive bleeding by chemical pleurodesis in lung transplantation. The bilateral pneumothorax was well controlled, and no recurrence has been observed. TPC is reliable procedure for management intractable bilateral SSP. For 12 high-risk patients with other underling pulmonary diseases on general poor conditions, a surgical intervention was performed in awake condition. The air leaks were stopped in 11 cases except for 1 case. The recurrence of pneumothorax after surgery was 2 cases. ASI for intractable secondary pneumothorax can be applicable to selected patients with deteriorated general condition.

Transvenous embolization of dural carotid cavernous fistulas: a series of 44 consecutive patients.

BACKGROUND AND PURPOSE: Endovascular TVE for DCCF is used for curative purposes, but serious complications can be caused with inadequate embolization. Our aim was to report clinical characteristics, angiographic findings, and results of endovascular TVE in patients presenting with DCCF. MATERIALS AND METHODS: We performed a retrospective analysis of 44 consecutive patients with DCCF treated by TVE. Approach routes, angiographic results, clinical outcomes, and complications were assessed. RESULTS: An approach via the internal jugular vein and inferior petrosal sinus was possible in 90% of patients, with complete occlusion of the fistula in 81.6% of patients. A minor residual shunt remained in 13.6% of patients, while a significant shunt remained in 4.5%. In 4 patients, add-on management with transarterial embolization was useful, and in 2 patients with residual shunt, radiosurgery was used. With long-term follow-up (6-40 months), we encountered recanalization/recurrence in 4 patients (9.1%). Complications were seen in the form of permanent morbidity in 3 patients (7%) and transient morbidity in 6 patients (14%). CONCLUSIONS: For endovascular treatment of DCCF, a transvenous approach was effective in most of our patients; however, some adverse effects were encountered. If AV shunts remain after transvenous treatment, additional modalities must be considered.

[Recurrence patterns and prognosis in lung cancer patients with positive pleural lavage cytology at surgery].

Recurrence patterns and prognosis in lung cancer patients with positive pleural lavage cytology (PLC) at surgery have not been completely understood. From January 2001 to October 2007, we performed PLC on 195 patients undergoing thoracotomy for lung cancer. Fourteen (7.2%) of 195 patients had positive PLC findings. Twenty seven patients who underwent limited surgery due to complication were excluded from the further investigation. Some form of recurrence was observed in 33 (21.2%) of 156 patients with negative PLC, and in 8 (66.7%) of 12 patients with positive PLC (p < 0.05). The local recurrence was observed in 13 (39.4%) of 33 patients who have recurrence with negative PLC and was observed in 4 (25%) of 8 patients who have recurrence with positive PLC (p = 0.45). The survival rate of patients with positive PLC was significantly worse than that of patients with negative PLC (p < 0.05), and was as low as that of patients with macroscopic malignant effusion. The multivariate analysis demonstrated PLC was independent prognostic factor. PLC is an easy procedure and is an important prognostic factor, and should be routinely performed in the lung cancer operation.

[Sternal resection and chest wall reconstruction for primitive neuroectodermal tumor of the sternum].

Primitive neuroectodermal tumor of the sternum is rare. A 59-year-old woman referred to our department with anterior chest pain and a tumor in the sternum. The patient was diagnosed as primitive neuroectodermal tumor of the sternum by core biopsy of the lesion. She received 2 cycles of preoperative chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide. She underwent a total sternectomy with resection of adjacent bilateral costal cartilages and sternal ends of the clavicles. The skeletal defect of chest wall was reconstructed by polypropylene mesh-resin sandwich. The myocutaneus defect was reconstructed by the pedicled latissimus dorsi myocutaneus flap and the bilateral breast flaps. The postoperative course was uneventful and adjuvant radiotherapy was started 6 weeks after the operation. She died of distant metastases 3 months after the operation, although this patient was free from local recurrence.

[Problems in donor lung evaluation for transplantation with regard to airway infection].

The shortage of donor organs has been 1 of the major obstacles to solid organ transplantation. Typical lung donor criteria include clear lung field on chest radiograph, adequate oxygenation, acceptable lung compliance, and satisfactory bronchoscopic findings. To extend usage of available donors, liberalization of donor lung selection criteria has been facilitated, however, marginal donor lungs must be used with discretion, because donor lung injury, especially that related to infection, has a potential leading to early post-operative death of the recipient. From March 2000 to December 2006, we evaluated 15 braindead donors and at least 1 of the lungs from 9 donors was judged suitable for transplantation. One of 9 recipients developed severe pneumonia cased by carbapenems-resistant Pseudomonas aeruginosa possibly originating from the donor lungs, eventually leading to death. The chest radiograph and oxygenation of the donor had been satisfactory, however, a moderate amount of mucopurulent secretions was observed by bronchoscopic inspection and the donor had been given a cefozopran for 9 days before the procurement operation. Remaining 8 recipients were free from air-way infection in the early postoperative period. We discuss the status and problems of donor lung evaluation for transplantation with regard to donor lung infection.

Lipid-mediated transbronchial human interleukin-10 gene transfer decreases acute inflammation associated with allograft rejection in a rat model of lung transplantation.

BACKGROUND: Transferring genes with immunoregulatory capacity to transplanted organs has the potential to modify allograft rejection (AR). We examined the effect of ex vivo lipid-mediated transbronchial human interleukin-10 (hIL-10) gene transfer on acute AR in a rat model of lung transplantation. METHODS: Left single lung transplantations were performed between a highly histoincompatible rat combination: Brown Norway to Lewis. The extracted donor left lung was intrabronchially instilled with a plasmid encoding hIL-10 or Escherichia coli beta-galactosidase (control), mixed with a cationic lipid. On day 6 posttransplantation, the degree of AR was graded histologically (stages 1-4) based upon pathological categories of inflammation: perivascular, peribronchial, and peribronchiolar lymphocytic infiltrates, edema, intraalveolar hemorrhage, and necrosis. RESULTS: The stage of AR in the IL-10 group (3.1 +/- 0.4) was significantly lower than the control group (3.8 +/- 0.4). Pathological scores for edema, intraalveolar hemorrhage, and necrosis in the IL-10 group (2.3 +/- 0.8, 0.3 +/- 0.5, and 0.3 +/- 0.5, respectively) were also significantly decreased compared with those in the control group (3.2 +/- 0.4, 2.2 +/- 0.8, and 1.2 +/- 0.4, respectively). CONCLUSION: Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR in a rat model of lung transplantation.

The DNA mismatch repair gene hMSH2 is a potent coactivator of oestrogen receptor alpha.

The DNA mismatch repair gene is a key regulator in the elimination of base-base mismatches and insertion/deletion loops (IDLs). Human MutS homologue 2 (hMSH2), originally identified as a human homologue of the bacterial MutS, is a tumour suppressor gene frequently mutated in hereditary non-polyposis colorectal cancer. Hereditary non-polyposis colorectal cancer is characterised by the early onset of colorectal cancer and the development of extracolonic cancers such as endometrial, ovarian, and urological cancers. Oestrogen receptor (ER) alpha and beta are members of a nuclear receptor (NR) superfamily. Ligand-dependent transcription of ER is regulated by the p160 steroid receptor coactivator family, the thyroid hormone receptor-associated proteins/the vitamin D receptor-interacting proteins (TRAP/DRIP) mediator complex, and the TATA box-binding protein (TBP)-free TBP associated factor complex (TFTC) type histone acetyltransferase complex. Here, we report the interaction between ER alpha/beta and hMSH2. Immunoprecipitation and glutathione-S-transferase pull-down assay revealed that ER alpha and hMSH2 interacted in a ligand-dependent manner, whereas ER beta and hMSH2 interacted in a ligand-independent manner. Oestrogen receptor alpha/beta bound to hMSH2 through the hMSH3/hMSH6 interaction domain of hMSH2. In a transient expression assay, hMSH2 potentiated the transactivation function of liganded ER alpha, but not that of ER beta. These results suggest that hMSH2 may play an important role as a putative coactivator in ER alpha dependent gene expression.