FR177995, a novel vacuolar ATPase inhibitor, exerts not only an inhibitory effect on bone destruction but also anti-immunoinflammatory effects in adjuvant-induced arthritic rats

There is considerable evidence that osteoclasts are involved in the pathogenesis of juxta-articular bone destruction in rheumatoid arthritis. Vacuolar ATPases (V-ATPases), which are highly expressed in the ruffled border membrane of osteoclasts, play a central role in the process of bone resorption, and V-ATPase inhibitors are effective in preventing bone destruction in several animal models of lytic bone diseases. Here, we evaluated for the first time the effects of V-ATPase inhibition in rats with adjuvant-induced arthritis (AIA) using FR177995, a novel V-ATPase inhibitor. FR177995 completely inhibited H(+) transport driven by V-ATPase, but exerted no effect on the H(+) transport activities of F- and P-ATPase, indicating that FR177995 is a specific inhibitor of V-ATPase. FR177995 acted directly on osteoclastic bone resorption and equally inhibited in vitro bone resorption stimulated by IL-1, IL-6 or PTH. In addition, FR177995 dose-dependently reduced retinoic acid-induced hypercalcemia in thyroparathyroidectomized-ovariectomized rats. When FR177995 was administered to AIA rats once a day, the loss of femoral bone mineral density was significantly improved. Moreover, indicators of cartilage damage (arthritis score and glycosaminoglycan content in the femoral condyles) and inflammation parameters (paw swelling volume, erythrocyte sedimentation rate and plasma sialic acid level) were found to be unexpectedly ameliorated. These results strongly suggest that V-ATPase may be an interesting drug target in the treatment of rheumatoid arthritis.     

Surgical Intervention for Malignant Fibrous Histiocytoma of the Lung: Report of a Case

Malignant fibrous histiocytoma (MFH) of the lung is rare, accounting for less than 0.2% of all pulmonary neoplasms, and an optimal treatment strategy has not yet been elucidated. We encountered a 62-year-old male patient with MFH of the lung who underwent a resection of the lymph node of recurrence 7 months after a lobectomy. We herein review 93 cases of pulmonary MFH in the literature, and discuss the surgical treatment for this disorder with special reference to lymph node involvement. Lymphogenic metastasis was observed in 14 of 72 cases (19%) who underwent surgical treatment. The 5-year survival rates for these reported patients with and without surgical treatment were 43% and 0% (P = 0.01) and the 5-year survival rates for “resected” patients with and without lymph node metastasis were 27% and 49%, respectively (P = 0.03). A complete resection with the systematic dissection of regional lymph nodes is therefore considered to positively contribute to the survival of patients with primary pulmonary MFH.     

Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene

We investigated three steps of neural precursor cell activation--proliferation, migration, and differentiation--in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide dismutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule-1 (Iba1), BrdU + glial fibrillary acidic protein (GFAP), or BrdU + highly polysialylated neural cell adhesion molecule (PSA-NCAM) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns, which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.     

Complication caused by use of fibrin glue in vessel transposition for trigeminal neuralgia

A 64-year-old man underwent microvascular decompression of the left superior cerebellar artery (SCA) for left trigeminal neuralgia (TN) using a sling of Teflon tape fixed to the tentorium with fibrin glue. The TN disappeared immediately after surgery, but recurred unusually rapidly at 2 weeks later at the same intensity as before. Second surgery revealed the SCA was suspended from the tentorium, but the trigeminal nerve was stretched and displaced superolaterally because of adhesion to the superior petrosal vein. The adhesion was thought to involve the fibrin glue used during the sling retraction procedure. The nerve was meticulously dissected from the adhesion, and the trigeminal nerve was placed in the correct position. The postoperative course was uneventful, and the TN disappeared completely. We recommend that the smallest amount of the fibrin glue possible be used to avoid adhesion to the surrounding neurovascular elements.     

Patch technique for repair of a dural tear in microendoscopic spinal surgery

A dural tear is a common but troublesome complication of endoscopic spinal surgery. The limitations of space make repair difficult, and it is often necessary to proceed to an open operation to suture the dura in order to prevent leakage of cerebrospinal fluid. We describe a new patch technique in which a small piece of polyglactin 910 is fixed to the injured dura with fibrin glue. Three pieces are generally required to obtain a watertight closure after lavage with saline. We have applied this technique in seven cases. All recovered well with no adverse effects. MRI showed no sign of leakage of cerebrospinal fluid.     

Should mediastinal nodal dissection be routinely undertaken in patients with peripheral small-sized (2 cm or less) lung cancer? Retrospective analysis of 225 patients.

OBJECTIVE: We retrospectively reviewed nodal status of the patients with peripheral small-sized lung cancer grouped by cell type and tumor size to evaluate the necessity of systematic nodal dissection in this group of patients. METHODS: From 1973 to 1998, 1713 patients underwent pulmonary resection for primary lung cancer in Kanazawa University. Among them, 225 patients (13.1%) with peripheral small-sized (2 cm or less) lung cancer underwent lobectomy and systematic nodal dissection were retrospectively reviewed. The maximum diameter of the tumor was measured on formalin-fixed surgical specimens. RESULTS: The histological types were adenocarcinoma in 170 (75.6%), squamous cell carcinoma in 20 (8.9%), small cell carcinoma in 19 (8.4%) and others in 16 (7.1%). Among 170 adenocarcinoma patients, 38 (22.4%) showed hilar or mediastinal lymph node metastases. No mediastinal lymph node metastasis was encountered in all squamous cell carcinoma (n = 20), adenocarcinoma < or = 1 cm (n = 16), small cell carcinoma < or = 1 cm (n = 4), and adenocarcinoma of Noguchi's classification type A or B (n = 24). CONCLUSIONS: Mediastinal nodal dissection would be unnecessary in the patients with peripheral small-sized lung cancer fulfilling these criteria: (1) squamous cell carcinoma < or = 2 cm; (2) adenocarcinoma < or = 1 cm; (3) localized bronchioloalveolar carcinoma < or = 2 cm without foci of active fibroblastic proliferation in histology (Noguchi's classification type A or B adenocarcinoma); (4) small cell carcinoma < or = 1 cm. Candidates fulfilling above criteria were 28.4% (64/225) of small-sized lung cancer and 10.9% of stage IA patients. The establishment of a universally accepted therapeutic strategy for small-sized lung cancer is indispensable in the clinical spread of various sort of limited resections.     

Carinal resection for bronchogenic carcinoma

The purpose of this study was to evaluate the results of carinal resection for bronchogenic carcinoma in our institute. From 1981 to 1999, 24 carinal resection were performed for squamous cell carcinoma (n = 19), adenoid cystic carcinoma (n = 2), small cell carcinoma (n = 1), adenocarcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). Nineteen underwent sleeve pneumonectomy, 2 had carinal resection without lung resection, 2 had carinal resection with right middle and lower lobectomy, and 1 had wedge pneumonectomy. In the patients with sleeve or wedge pneumonectomy, there were 5 operative death and 3 patients had survived for more than 3 years. Two patients with low-grade malignant tumors underwent carinal resection without lung resection and survived more than 10 years. We believe that limited carinal resection for low-grade malignant tumors are safe and valuable procedure. Careful selection of patients with sleeve or wedge pneumonectomy is mandatory.     

Malignant pleural mesothelioma

Malignant pleural mesothelioma carries a poor prognosis, for which no standard therapy has been established. We report 15 cases of malignant pleural mesothelioma experienced since 2000 focusing on their clinical features. They included 14 male and 1 female aged 38 to 81 (62.8 on average) years. All patients were diagnosed by pleural biopsy under thoracoscopic guidance. Histology of the pleural biopsy specimen showed epithelial mesothelioma in 8 patients, biphasic mesothelioma in 3, sarcomatous mesothelioma in 2 and desmoplastic malignant mesothelioma (DMM) in 2. Twelve patients received chemotherapy. Of these, 3 were followed by surgery. In addition to 2 of these 3 patients, 2 underwent extrapleural pneumonectomy (EPP) without adjuvant treatment. Remaining 1 received palliative treatment only. As a result, 6 patients are surviving, 7 died of primary diseases and 2 died of other diseases. The longest survival time with chemotherapy is 41 months in a surviving patient with epithelial mesothelioma and that with EPP is 25 months in a surviving patient with DMM. The 2-year survival rate of the 14 patients was 44.4% and the median survival time in patients with epithelial mesothelioma was 30.6 months.     

Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation.

In the present study, the results of living donor liver transplantation (LDLT) for 125 hepatocellular carcinoma (HCC) patients were analyzed to determine optimal criteria exceeding the Milan criteria (MC) but still with predictably good outcomes. On the basis of pretransplant imaging studies, 70 patients met the MC, and 55 patients did not. Patients who exceeded the MC but presented with 相似文献