Role of Toll-like Receptor 4 Expressed by Fibroblasts in Allograft Fibrosis in Mouse Orthotopic Tracheal Transplantation.

Development of chronic lung allograft dysfunction involves various alloimmune-independent insults including those mediated by Toll-like receptor (TLR) signaling, which is known to activate alloimmune responses. We hypothesized that TLR signaling may also contribute to the activation of fibroblasts and promoting allograft airway fibrosis. Mouse orthotopic tracheal transplants were conducted between major histocompatibility complex (MHC)-mismatched Balb/c donor and wild-type C3H or C3H-derived TLR4 mutant recipients (nonfunctional TLR4). Immunohistochemistry on day 21 showed significantly smaller alpha-smooth muscle actin (α-SMA)-positive areas in TLR4 mutant recipients than wild-type recipients (P = .01). No difference was found for CD3+ T-cell infiltration. Proliferation of alloreactive T cells derived from the recipient spleen showed no difference between TLR4 mutant and wild-type recipients in a mixed lymphocyte reaction. The effect of TLR4 signaling was examined in primary pulmonary fibroblast cultures both with lipopolysaccharide (LPS) and transforming growth factor (TGF)-ß1. Stimulation with LPS significantly increased expression of α-SMA mRNA in wild-type fibroblasts cultured with TGF-ß1 compared with the control without LPS (P = .001). Taken together, these findings suggest disruption of TLR signaling leads to reduced activation of fibroblasts without affecting T-cell infiltration and proliferation in this model. TLR4-mediated activation of fibroblasts may be a potentially important mechanism of allograft remodeling.

Epithelial to mesenchymal transition in murine tracheal allotransplantation: an immunohistochemical observation.

BACKGROUND: Aberrant epithelial repair is a crucial event in the airway remodeling that characterizes obliterative bronchiolitis (OB) in transplanted lungs. Recent data from experiments using epithelial cell lines and human airway tissues from lung transplant recipients suggest that epithelial to mesenchymal transition (EMT) plays an important role in OB. The aim of this study was to clarify whether EMT is involved in airway remodeling in an animal model. METHODS: We performed orthotopic tracheal transplantation from BALB/c to C57BL/6 mice with from BALC/c to BALB/c mouse grafts as controls. Five allogeneic and 3 syngeneic recipients were humanely killed at predetermined postoperative days 2-12 as well as 14 and 21. Histology was evaluated using hematoxylin-eosin (H&E) staining. We studied the expression of specific markers, including E-cadherin, an epithelial marker; α-smooth muscle actin (SMA), and S100A4, mesenchymal markers, and zinc finger E-box-binding homeobox 1 (ZEB1), an EMT-related transcription factor. RESULTS: Histologic assessment of serial H&E stains of allogeneic grafts showed remarkable pseudostratified respiratory epithelium with subepithelial inflammatory cell infiltration, as well as denuded and flattened epithelium and subepithelial fibrosis. The dynamic epithelial changes occurred earlier than the subepithelial fibrosis. Immunohistochemical evaluation indicated the emergence of α-SMA- positive epithelial cells that were most prominent on day 7. The expression of E-cadherin was attenuated in α-SMA-positive epithelial cells. S100A4 was also expressed in epithelial cells. A few days before the intraepithelial expression of α-SMA, ZEB1 emerged in the nuclei of epithelial cells. CONCLUSIONS: We observed expression of an EMT-related transcription factor and mesenchymal markers along with the attenuation of epithelial marker expression in epithelial cells, several days before prominent subepithelial fibrosis formation, results that suggest epithelial cells to play an important fibrosis role in airway remodeling during epithelial to mesenchymal transition.

Erosion bleeding as a late complication of chest wall reconstruction with a Dacron mesh silicone prosthesis.

A 71-year-old man who had undergone chest wall resection and reconstruction with a Dacron mesh silicone prosthesis for chondrosarcoma 23 years previously presented with a chest wall hematoma. Since the hematoma was found to increase in size over time, we performed an operation to achieve hemostasis. Operative findings showed that the prosthesis had separated into three sheets.

[Thymoma with synchronous pulmonary metastasis; report of a case].

We report a resected case of thymoma with a solitary pulmonary metastasis. A 63-year-old woman had pointed out a solitary nodule in right lung field on chest X-ray. Computed tomography (CT) scan showed an anterior mediastinal tumor and a solitary lung nodule in the right lower lobe. Extended thymectomy and partial resection of right lung was performed. Pathological diagnosis showed an invasive thymoma (type B3) and a pulmonary metastasis. Post operative radiotherapy was administered and she is doing well 19 months following the resection. Thymoma with a solitary synclonous pulmonary metastasis is rare and is classified into Masaoka stage IVb. Generally, thymoma cases with distant metastasis are not indication for operation. But, if radical resection is possible, operation is recommended for good prognosis.

[Posterior mediastinal hemangioma successfully resected with cardiopulmonary bypass; report of a case].

Mediastinal hemangioma is a rare tumor. We report a case of a 62-year-old woman with a posterior mediastinal hemangioma. She had a history of right breast cancer and a follow-up chest radiography revealed a mass located in the left posterior mediastinum. The size was about 80 mm in diameter. The tumor surrounded the descending thoracic aorta and involved intercostal arteries. Complete excision could be achieved by decompressing the descending aorta with the aid of partial cardiopulmonary bypass and the aortic cross-clamp. Histologically, the tumor was diagnosed as a benign hemangioma. It was reported that hemangioma would reccur after subtotal excision. To employ cardiopulmonary bypass was a very effective approach for the purpose of complete excision in our case.

[Pulmonary thromboembolism after lung resection in patients with schizophrenia; report of 2 cases].

We report 2 cases of pulmonary thromboembolism after lung resection in patients with schizophrenia. The first case is a 67-year-old woman. She underwent right lower lobectomy for primary lung cancer and suddenly felt dyspnea 2 days after the operation. She was diagnosed pulmonary thromboembolism by computed tomography (CT) and lung perfusion scintigram, and recoverd soon. The second case is a 42-year-old man. He underwent partial resection of the right lung for metastatic germ cell tumor. Six days after the operation, he fell into acute respiratory failure and died in spite of resuscitation. The autopsy showed that the cause of death was pulmonary thromboembolism. Because patients with schizophrenia have high-risk of pulmonary thromboembolism, extreme care must be exercised to avoid it.

Polyunsaturated hydrocarbons in the hemolymph: biosynthetic precursors of epoxy pheromones of geometrid and arctiid moths.

Female moths of many species in Geometridae, Arctiidae and some other macrolepidopteran families produce epoxy pheromones, which are probably derived from polyunsaturated hydrocarbons. In order to understand a biosynthetic site, hemolymph from both sexes of two geometrid species, Ascotis selenaria cretacea and Hemerophila artilineata, and one arctiid species, Spilosoma imparilis, was shaken with n-hexane and the solvent extracts were analyzed by GC-MS. Each extract of the female hemolymph sex-specifically included polyunsaturated hydrocarbons corresponding to the pheromonal epoxy components in addition to many saturated hydrocarbons, but no epoxy compounds were detected in it. Based on this analysis, deuterated polyunsaturated hydrocarbons were injected into the abdomens of two geometrid females, and the labeled epoxy components were successfully yielded from the pheromone glands. This result indicated that the polyunsaturated hydrocarbons occurring in the female hemolymph were direct pheromone precursors, which might be produced outside the pheromone gland, probably in oenocytes associated with abdominal epidermal cells or in the fat body, and transported to the pheromone gland via the hemolymph for their epoxydation and emission into the atmosphere.

[Metastatic sternal tumor from thyroid papillary carcinoma; report of a case].

A 68-year-old male was referred to our department for treatment of a metastatic sternal tumor in the manubrium sterni. Primary lesion was papillary carcinoma of the left lobe of the thyroid gland. Total thyroidectomy, cervical lymph node dissection, resection of manubrium sterni with concomitant resection of bilateral clavicles, 1st ribs and 2nd ribs, and chest wall reconstruction using Marlex Mesh were performed on January 29, 2001. Considering relatively good prognosis and good response to multimodality therapy, surgical resection of sternal metastatic lesion from differentiated thyroid cancer seems to be a choice of therapy as a part of multimodality approach, including surgery, radioiodine and external radiation therapy, to thyroid cancer with systemic spread.

[A comparison of propofol and midazolam in sedation of mechanically-ventilated postoperative patients].

To compare the quality of sedation using propofol (n = 8) vs midazolam (n = 7) we evaluated their effectiveness, safety, and recovery time after their continuous infusion in patients who required mechanical ventilation after cervical spine surgery. We also calculated the cost of drugs used during the mechanical ventilation. In addition, processed electroencephalogram (pEEG) was monitored employing spectral edge frequency 90 (SEF 90) as an indicator of sedation. Both drugs produced good sedation without any complication. The patients who had received propofol were extubated significantly earlier than those who had received midazolam (P; 35 +/- 18 mins, M; 97 +/- 55 mins). However, the mean drug cost in the propofol group was five times higher than that in the midazolam group (P; yen 15,881 +/- 7,788, M; yen 3,355 +/- 1,187). There was no correlation between the value of SEF 90 and the depth of sedation during mechanical ventilation. In conclusion, propofol exhibited the shorter recovery time after cessation of the continuous infusion than midazolam, but it costed five times compared with midazolam. SEF 90 failed to indicate the depth of sedation during mechanical ventilation.

Primary low-grade B-cell lymphoma in mucosa-associated lymphoid tissue of the lung.

A 67-year-old asymptomatic woman was referred to our department for treatment for a left lung tumor. The tumor was 40 mm in diameter and was present in the left lower lobe. A primary low-grade B-cell lymphoma in the mucosa-associated lymphoid tissue of the lung was suspected after a trans-bronchial lung tissue biopsy. Systemic screening revealed no other organ involvement, and the tumor was considered to be a primary lung tumor. A left lower lobectomy with hilar and mediastinal lymph node sampling was performed. Pathological examination revealed centrocyte-like cells that expressed CD20. These cells had invaded the bronchiolar epithelium to form lymphoepithelial lesions. The pathological diagnosis was confirmed to be primary low-grade B-cell lymphoma in the mucosa-associated lymphoid tissue of the lung. The origin of this tumor type in the lung is relatively rare.

[A case of primary lung adenocarcinoma with diffuse calcification in the tumor by psamoma bodies].

A 78-year-old asymptomatic woman was referred to our department for the treatment of a right lung tumor. The patient had been suffering from rheumatoid arthritis and followed up in outpatient clinic. On March 6, 1995, abnormal shadow in the right upper lobe was pointed out by routine chest X-ray. Chest CT revealed calcification in the shadow, and benign lesion, such as old pulmonary tuberculosis, was suspected. During follow-up, the size of the shadow and calcification area in the shadow gradually increased. Malignancy was suspected based on the increasing size of the tumor. On July 12, 2000, video-assisted right upper lobectomy with hilar and mediastinal lymph node sampling was performed. Pathological examination revealed that the tumor was primary lung adenocarcinoma containing psamoma bodies in the tumor.

Tonsillar metastasis from large cell carcinoma of the lung.

A 52-year-old female was referred to our department for treatment of a left lung tumor, 80 mm in diameter, arising in the left S1 + 2. The patient's chief complaint was persistent dry cough and spiking fever. Left upper lobectomy with hilar and mediastinal lymph node dissection (ND2a) was performed, and the pathological diagnosis was primary large cell carcinoma of the lung, p-T3N0M0. At one week after being discharged, the patient visited our outpatient clinic complaining of a sore throat. A tumor in the right tonsil was discovered, and excisional biopsy revealed it to be metastasis from the large cell carcinoma of the lung. Right cervical lymph node metastasis was also detected, and the patient was treated by combined chemo-radiotherapy, resulting in a complete remission.

Thoracoscopic surgery and conventional open thoracotomy in metastatic lung cancer.

BACKGROUND: We performed a retrospective comparison of the oncological outcome of thoracoscopic surgery for pulmonary metastasis with that of conventional open thoracotomy. METHODS: The patient population for our retrospective comparison was comprised of 45 patients undergoing pulmonary resections via video-assisted thoracoscopy (thoracoscopy group) and 55 undergoing similar resections by open thoracotomy (open group) for pulmonary metastases between 1994 and 1999. RESULTS: Solitary metastasis was resected more frequently with thoracoscopy than open thoracotomy. There were no significant intergroup differences in rates of local recurrence from the initial pulmonary resection site. The actuarial 1-year, 2-year, and 3-year survival rates were, respectively, 82.8%, 70.0%, and 62.3% in the thoracoscopy group and 93.6%, 64.6%, and 52.7% in the open group. The rates of pulmonary recurrence and survival also did not differ significantly between the two groups with solitary metastases. CONCLUSION: Thoracoscopic surgery for metastatic lung disease appears to be feasible as long as the preoperative metastatic tumor evaluation using chest computed tomography (CT) is accurate.

[Preparation of a gel-forming ointment base applicable to the recovery stage of bedsore and clinical evaluation of a treatment method with different ointment bases suitable to each stage of bedsore].

A novel ointment base suitable for the treatment of bedsore at the recovery stage was developed by the use of hydroxypropyl methylcellulose (HM-HPMC) modified on the basis of the hydrophobicity. A considerable sustained release of drug (minocycline hydrochloride) formulated to the ointment (T50 of 170 min) was attained with a macrogol ointment (MO) mixed with the HM-HPMC and Carbopol (CP) of the formulating ratio of 3:7. It was also found that a change in the formulating ratio of HM-HPMC and CP lead to a change in the drug release rate. The water absorption property of the ointment base, required to absorb on exudative solution in applying to the bedsore treatment, was as high as that of an ointment base containing hydroxypropyl cellulose (HPC) and CP reported in our previous paper. We clinically evaluated the effectiveness of the bedsore treatment, in which different ointment bases were applied to patients at different stages of the bedsore. A total of 22 cases were divided into two categories for applying to the different treatments. One category comprised of 11 subjects was treated with a povidone-iodine sugargel, which was the conventional method in our hospital, while the other 11 subjects were treated by the use of the newly developed ointment bases in consideration for the different stages of the bedsore. In comparison of the clinical results with the healing index, we ascertained that the latter method was significantly more efficacious (p < 0.01-0.05) than the conventional one. The effectiveness was emphasized in treating the intractable bedsore classified into the grades IV and V. Therefore, we confirmed that the newly developed ointment base formulation is useful in treating bedsore at each stage.

Effects of lung metastasectomy on respiratory function.

OBJECTIVE: The effects of lung metastasectomy on respiration were evaluated. SUBJECTS: From 1961 to 1999, 203 patients underwent lung metastasectomy. Of these, 102 patients who had undergone only partial lung resection, had undergone sufficient respiratory function testing, and had not suffered from other lung disease were included. RESULTS: Unilateral thoracoscopic surgery caused less decrease in percent vital capacity than surgery through a posterolateral thoracotomy, in both the early (rate of decrease: 16.2 +/- 9.1 vs. 33.0 +/- 12.0%, p < 0.01), and the late postoperative period (2.0 +/- 4.5 vs. 17.8 +/- 6.0%, p < 0.0001). Two thoracoscopic operations caused less decrease in percent vital capacity than 2 operations through a posterolateral thoracotomy (21.3 +/- 13.8 vs. 61.1 +/- 8.1%, p = 0.02). Bilateral metastasectomy through a median sternotomy caused less decrease in percent vital capacity than that through posterolateral thoracotomies (45.5 +/- 13.7 vs. 60.8 +/- 8.8%, p < 0.05). Four (36%) of 11 patients who had undergone 3 or more metastasectomies exhibited dyspnea of degree 3 or higher on the Hugh-Jones classification. CONCLUSIONS: Thoracoscopic metastasectomy and metastasectomy through a median sternotomy caused less restrictive respiratory dysfunction than metastasectomy through a posterolateral thoracotomy. Since metastatic lung disease often necessitates repeated metastasectomy, and repeated metastasectomy often causes severe restrictive respiratory dysfunction, metastasectomy should be performed with a less invasive procedure.

[Marked bradycardia during anesthetic induction treated with temporary cardiac pacing in a patient with latent sick sinus syndrome].

A 59 year-old woman with latent sick sinus syndrome was scheduled to undergo ophthalmic surgery including phacoemulsification and aspiration, vitrectomy, photocoagulation and intraocular lens under general anesthesia. Preoperative ECG showed sinus rhythms of 77 bpm without bradycardia or a sinus pause. Total intravenous anesthesia with propofol, fentanyl, ketamine and vecuronium was employed for the induction of anesthesia immediately followed by severe bradycardia with a rate of 36-40 bpm including sinus arrest and atrio/nodal escaped beats. Intravenous atropine was ineffective to restore the heart rate and then urgent temporary pacing was successfully applied to overcome bradycardia. The patient recovered uneventfully from anesthesia. She complained of being dizzy and faint with prominent bradycardia due to sick sinus syndrome three months after the surgery. Therefore she underwent permanent cardiac pacemaker implantation successfully. Temporary pacing is mandatory when anesthesia is given to surgical patients with latent sick sinus syndrome.

Malignant fibrous histiocytoma in the anterior mediastinum.

The origin of a malignant fibrous histiocytoma in the anterior mediastinum is rare. A 71-year-old man was referred to our department for treatment of a tumor 15 cm in diameter originating in the anterior mediastinum. Malignant fibrous histiocytoma was suspected after a percutaneous needle biopsy. Systemic screening showed no other organ involvement, and the tumor was considered to be a primary mediastinal tumor. The tumor, resected through a median sternotomy, was well encapsulated and resection was complete. The pathological diagnosis was malignant fibrous histiocytoma originating in the anterior mediastinum.

Thoracoscopic resection of the pulmonary aspergilloma: report of two cases.

Pulmonary aspergillomas causing hemoptysis were successfully resected through videothoracoscopy in two cases. We removed an aspergilloma located in the right lower lobe of the lung in a 48-year-old woman with a bronchial cyst and rheumatoid arthritis. We also removed an aspergilloma located in the left upper lobe of the lung in a 59-year-old man with emphysematous bullae and diabetes mellitus. In both cases, the aspergillomas were removed by pulmonary wedge resection through scheduled thoracoscopy.

Allogenicity of cryopreserved human fibroblasts: cryopreservation does not downregulate the allogenicity of fibroblasts making up the matrices of allografts.

BACKGROUND: Although cryopreserved tissue allografts are being widely used, long-term degeneration of implanted cryopreserved allografts has become a problem. Although immunologic rejection has been suggested to play a part in this degeneration, cryopreserved allografts are considered to be less immunogenic than fresh allografts. OBJECTIVE: We investigated the effect of cryopreservation on the allogenicity of the fibroblasts that make up the matrices of allografts. METHODS: Fibroblast cell strains obtained from surgically resected lung specimens were used. Allogenicity-related antigens expressed on the cell surface (human leukocyte antigen 1, human leukocyte antigen 2, and intercellular adhesion molecule 1), stimulation indices during 1-way mixed lymphocyte-fibroblast cell culture, and proliferation indices of freshly passaged fibroblasts and cryopreserved fibroblasts stored for 1, 4, and 24 weeks were examined. Flow cytometric analysis with monoclonal antibodies was used to test for cell surface antigens, and a colorimetric methyl-thiazol-diphenyl-tetrazolium assay was used to assess stimulation indices and fibroblast proliferation indices. The effect of exogenous interferon-gamma on the degree of expression of human leukocyte antigen 1, human leukocyte antigen 2, and intercellular adhesion molecule 1 was examined simultaneously. RESULTS: The proliferation indices of fibroblasts were well maintained by cryopreservation. Expression of human leukocyte antigen 1, human leukocyte antigen 2, and intercellular adhesion molecule 1 by fibroblasts was significantly upregulated by interferon-gamma, and cryopreservation did not downregulate this expression. CONCLUSION: Our study suggests that although the fibroblast cell component may be beneficial in restoring allograft function properties initially, it may render the implanted allograft more immunogenic, ultimately resulting in greater rejection and inflammatory responses by the host and, in turn, degeneration of the graft.

Flow cytometric analysis of lymphoid cells in thymic epithelial neoplasms.

OBJECTIVE: There have been conflicts concerning the criteria for diagnosing malignant epithelial neoplasms of thymic origin. To differentiate thymic carcinomas from thymomas, the maturation stage of T-lineage lymphoid cells infiltrating thymomas and thymic carcinomas was examined by flow cytometry to associate it with the degree of tumor malignancy. METHODS: Multidimensional flow cytometric analysis was performed on the lymphoid cells extracted from 27 thymic epithelial neoplasms (14 encapsulated thymomas, ten invasive thymomas, and three thymic carcinomas) by using anti-CD3, -CD4, -CD8, -CD10, -CD20, -CD38, -CD45RA, and -CD45RO monoclonal antibodies. RESULTS: CD4 and CD8 were co-expressed on 76.8% of the lymphoid cells in encapsulated thymoma (N=14), 59.2% in invasive thymoma (N=10), and 6.7% in thymic cancer (N=3). The percentage of CD4- or CD8- single positive cells was 11.4% in encapsulated thymoma, 23.9% in invasive thymoma, and 77.7% in thymic cancer. The percentage of CD10-positive cells was 20.8% in encapsulated thymoma, 13.2% in invasive thymoma, and 6.0% in thymic cancer. The percentage of CD20-positive cell was 2.6% in encapsulated thymoma, 3.3% in invasive thymoma, and 31.6% in thymic cancer. There were significant statistical differences in the percentages of CD4/CD8 double positive cells, CD4- or CD8-single positive cells, CD10-positive cells and CD20-positive cells among the three groups. Two cases classified as invasive thymoma by pathohistological examination, however, showed the infiltration of mature lymphocytes like as thymic cancers. CONCLUSIONS: CD4+CD8+ or CD10+ T-lineage cells were the most reliable markers of the benignancy of thymic epithelial tumors. CD4- or CD8-single positive cells or CD20-positive cells were characteristic in thymic carcinoma. Flow cytometry on the maturity of lymphoid cells infiltrating thymic epithelial tumors was feasible for determining their degree of malignancy. Some invasive thymomas showed the intermediate characteristics with thymomatous epithelia and mature lymphoid cells.