QSAR model to predict Kp,uu,brain with a small dataset, incorporating predicted values of related parameter.

The unbound brain-to-plasma concentration ratio (Kp,uu,brain) is a parameter that indicates the extent of central nervous system penetration. Pharmaceutical companies build prediction models because many experiments are required to obtain Kp,uu,brain. However, the lack of data hinders the design of an accurate prediction model. To construct a quantitative structure-activity relationship (QSAR) model with a small dataset of Kp,uu,brain, we investigated whether the prediction accuracy could be improved by incorporating software-predicted brain penetration-related parameters (BPrPs) as explanatory variables for pharmacokinetic parameter prediction. We collected 88 compounds with experimental Kp,uu,brain from various official publications. Random forest was used as the machine learning model. First, we developed prediction models using only structural descriptors. Second, we verified the predictive accuracy of each model with the predicted values of BPrPs incorporated in various combinations. Third, the Kp,uu,brain of the in-house compounds was predicted and compared with the experimental values. The prediction accuracy was improved using five-fold cross-validation (RMSE = 0.455, r2 = 0.726) by incorporating BPrPs. Additionally, this model was verified using an external in-house dataset. The result suggested that using BPrPs as explanatory variables improve the prediction accuracy of the Kp,uu,brain QSAR model when the available number of datasets is small.

[Invasive thymoma with thymic cyst; report of a case].

A 27-year-old woman was pointed out an abnormal shadow on chest X-ray in 1999. Because of the enlargement of the chest abnormal shadow, she was admitted to our hospital in 2000. Chest computed tomography (CT) revealed anterior mediastinal solid mass with cystic lesion. A thymoma was suspected. The tumor was removed in June 2000, through a longitudinal incision of the sternum. There was a severe adhesion between the tumor and the right brachiocephalic vein. Histological examination revealed a thymoma with thymic cyst. The thymoma had a capsular invasion (stage II). There were few reports for cases of thymoma with thymic cyst.

[Malignant solitary fibrous tumor of the pleura; report of a case].

A 68-year-old female was admitted to our hospital for further examination of abnormal shadow on chest X-ray. Needle biopsy could not establish pathological diagnosis. Three years later, chest computed tomography (CT) revealed the tumor was enlarged. We suspected it was a malignant tumor, and resected by video-assisted thoracoscopy. The tumor occurred from the right middle lobe, and intraoperative diagnosis was malignant tumor. We added middle lobectomy. Histological examination revealed that tumor was malignant solitary fibrous tumor.

[Sentinel node biopsy for staging of small peripheral lung cancer].

UNLABELLED: Is it possible to choose between limited lymph node sampling and systematic lymphadenectomy from the distribution of sentinel lymph nodes in patients with small lung cancer less than 2 cm in diameter? METHODS: Twenty-four patients with cN0M0 lung cancer less than 2 cm in diameter were enrolled. A radioisotope tracer (Tc-99 m tin colloid or phyphate) was injected in the vicinity of the tumor before surgery under computed tomography (CT) guidance. The radioactivity of each resected lymph node was measured separately with a hand-held gamma probe after complete tumor resection. Sentinel nodes were identified and the accuracy of sentinel node mapping was examined. RESULTS: Successful radionuclide migration occurred in 20 of the 24 patients (83.3%). There were 21 N0 patients and 3 N-positive patients. There was no false-negative case, so the sensitivity and the specificity was 100%. The lobar lymph nodes were identified as sentinel nodes more frequently than other lymph nodes. CONCLUSION: The sentinel node concept is valid in patients with small lung cancer less than 2 cm in diameter. We believe that, if sentinel nodes are identified, sentinel node mapping can allow the accurate intraoperative diagnosis of pathological N0 status in patients with small peripheral lung cancer.

[Recurrent tuberculous abscess in the chest wall; report of a case].

A case of recurrent tuberculous abscess in the chest wall which was successfully treated by resection of the rib and transposition with a latissimus dorsi muscle flap is reported. A 70-year-old man was admitted to the hospital for the purpose of receiving tuberculostatic treatment after an operation for tuberculous abscess in the chest wall at another hospital. When he first visited the another hospital, he had complained of a left chest wall tumor and Mycobacterium tuberculosis was isolated from the pus. After admission to the hospital, tuberculous abscess recurrenced in the left chest wall 2 months after the operation. We performed resection of the abscess, 5th and 6th ribs, as well as transposition of the latissimus dorsi muscle flap. There have been no signs of recurrence and is followed in the clinic, as of 4 months after the operation. We think that resection of the abscess, ribs, and, transposition of the muscle flap are useful methods for tuberculous abscess in the chest wall.

[A case of bronchioloalveolar carcinoma diagnosed by a segmental resection].

A 66-year-old man who underwent an extirpation of thymoma in stage I on September 16 1997 was followed in the outpatient clinic. In October 1998, a chest CT scan revealed a 2.0 x 1.0 cm faint frosted glass like shadow in the right S9. On September 13 1999, the patient was admitted to the hospital for close examination. Two times of transbronchial lung biopsy could not offer any clear diagnosis because the lesion was present so as to encircle the central segment of the B9 gronchus. A segmental resection (S9 + 10) under thoracotomy was performed. Intraoperative frozen section diagnosis was bronchioloalveolar carcinoma (type A according to Noguchi's classification), and a resection of the remnant lower lobe and mediastinal lymph nodes dissection (ND 2 a) were added. With expected increase in frequency of detecting early pulmonary cancer's through CT, clinical cases for which we are obliged to diagnosed the disease by segmental resection may increase, if the lesion develops in the vicinity of the hilum of lung like this case.

Pulmonary lymphoma of large B-cell type mimicking Wegener's granulomatosis.

A 27-year-old man with a primary pulmonary lymphoma of large B-cell type is described. Symptoms involved both the upper and lower respiratory tract. A chest roentgenogram showed a dense mass with cavitation. Transbronchial biopsy specimens revealed no atypical cells, rather they demonstrated granulomatous infiltration and vasculitis consistent with but not conclusively diagnostic of Wegener's granulomatosis. The pulmonary mass became smaller after sulfamethoxazole-trimethoprim therapy. These features suggested Wegener's granulomatosis. However, an open biopsy specimen was diagnostic for diffuse lymphoma of large B-cell type. High-grade pulmonary lymphoma should be considered in the differential diagnosis of patients with clinical and pathologic features suggesting Wegener's granulomatosis.

[A case of schwannoma arising in brachial plexus with intrathoracic extension].

A case of benign schwannoma arising in the brachial plexus with intrathoracic extension was presented. The patient was a 55-year-old man, who was pointed out an abnormal shadow in the left apical region on routine chest X-ray examination. MRI showed that the mass extended to the lowest trunk of the brachial plexus. He had no complaint. Therefore, a diagnostic operation was performed. The tumor was subcapsularly resected with thoracoscopic surgery. Histopathological examination revealed a schwannoma (Antoni type A and B). It should be kept in mind that tumors arising in the brachial plexus are a probable differential diagnosis for tumors at the pulmonary apex, even if no neurological symptoms are seen in the upper extremities.

[Video-assisted thoracoscopical surgery for pericardial cyst: report of two cases].

Two cases of pericardial cyst are reported. Case 1: A 51-year-old man, was admitted to the hospital because of an abnormal shadow on a chest CT scan. We confirmed a cystic mediastinal tumor situated between the superior vena cava and azygos vein. The cystic tumor was excised with a video-assisted thoracoscopic surgical procedure. Histopathological examination revealed a mesothelial-lined structure. Patient 2, a 34-year-old woman was admitted to the hospital because of an abnormal shadow on a chest radiographic film. Chest CT scan showed a cystic mediastinal tumor. The cystic tumor was excised with a video-assisted thoracoscopic surgical procedure. Histopathological examination revealed a mesothelial-lined structure. We would recommend video-assisted thoracoscopic surgery which is of great value in the treatment of pericardial cyst.

[A case report of a mediastinal bronchogenic cyst with back pain].

We performed thoracoscopic surgery for a mediastinal bronchogenic cyst with complaining of back pain. The patient, a 38-year-old male, was admitted with an abnormal shadow on chest X-ray. Chest CT showed a localized tumor on the mediastine. MRI showed a cyst. Under thoracoscopy the tumor was based on parietal pleura and movable in chest cavity. We concluded that back pain was caused by a stimulus of a nerve in parietal pleura. Pathological diagnosis was a bronchogenic cyst.

[An effective case of a new biological adhesive agent, gelatin-resorcinol formaldehyde-glutaralhyde glue (GRFG-glue) in treating refractory pulmonary fistula following lobectomy for pulmonary aspergilloma].

We report a successful case of thoracoscopic therapy using a new biological adhesive agent, Gelatin-Resorcinol Formaldehyde glue (GRFG glue) for refractory pulmonary fistula. A 69-year-old male underwent right upper lobectomy for lung aspergilloma. Air leakage began 11 days after lobectomy. Closing alveolar fistula was performed 28 days after first operation. Relapsing air leakage began 2 days after second operation. The insertion of fibrin glue through thoracoscope at two times was not effective for refractory pulmonary fistula. But the insertion of GRFG glue was effective to close the fistula completely.

[A resected case under thoracoscopic surgery of bilateral pulmonary metastases of renal cell carcinoma ten years after radical nephrectomy].

A 68-year-old male had received a left nephrectomy for renal cell carcinoma of the clear cell type in October, 1987. He had been given Interferon alpha (IFN alpha) for one year since then. He was referred to our hospital for bilateral abnormal shadows on the chest roentgenogram in December, 1997. He underwent a video-assisted thoracoscopic biopsy of bilateral lung in January, 1998, 11 years after his nephrectomy. The resected specimens contained a coin lesions measuring approximately 2 cm in diameter, and the lesions were microscopically diagnosed as a renal cell carcinoma of the clear cell type metastatic to the lung. The patient is doing well with no signs of re-recurrence five months after the resection of the metastatic lesion.

[A case of intrathoracic lipoma arising from the chest wall resected by video-assisted thoracoscopic surgery].

We present a case of lipoma arising from the chest wall spreading into the thoracic cavity. Although asymptomatic, a 65-year-old female was pointed out an abnormal shadow on the chest X-ray film taken at the mass survey. The tumor, measuring 3.4 x 3.0 x 2.0 cm in diameter, was surgically removed under thoracoscopic visualization through a small thoracotomy incision of lt. 1st intercostal space, and the diagnosis of lipoma was confirmed postoperatively by histopathologic examination.

Role of angiotensin II, endothelin-1, and nitric oxide in HgCl2-induced acute renal failure.

To elucidate the mechanisms underlying the development of HgCl2-induced acute renal failure (ARF), we examined the expression of endothelin (ET)-1, endothelial (e) nitric oxide synthase (NOS) and inducible (i) NOS, and a role of angiotensin II (ANG II) and tumor necrosis factor (TNF) in glomeruli and cortices from rats at 20 h after exposure of HgCl2. Prepro-ET-1 and iNOS mRNA were significantly increased in glomeruli and cortices from rats with HgCl2-induced ARF. However, eNOS mRNA was markedly decreased in glomeruli of rats with HgCl2-induced ARF. Blockade of the action of endogenous ANG II with TCV-116, an ANG II receptor type 1 antagonist, or prior administration of TNF antibody (Ab) neutralizing TNF bioactivity or aminoguanidine, an iNOS inhibitor, substantially suppressed the increase in the expression of prepro-ET-1 or iNOS mRNA seen in rats with HgCl2-induced ARF. Both TCV-116 and TNF Ab had no effects on the expression of eNOS mRNA. The abundance of ET-1, iNOS, and eNOS proteins was paralleled by the magnitude of each mRNA expression. Additionally, the aggravation of blood urea nitrogen and serum Cr observed in rats with HgCl2-induced ARF were significantly ameliorated together with the alleviation of proximal tubule epithelial cell injury when the expression of prepro-ET-1 or iNOS mRNA was blunted by prior administration of TCV-116 or prior injection of TNF Ab or aminoguanidine. These observations indicate that ANG II, ET-1, and NO may play an important role in the progression of HgCl2-induced ARF through the acceleration of proximal tubule epithelial cell injury and the deterioration of glomerular hemodynamics. In HgCl2-induced ARF, the gene expression of ET-1 or iNOS is at least in part up-regulated at the transcription level by endogenous ANG II or TNF.

[A resected case of a bronchiolo-alveolar cell carcinoma of the lung accompanying pneumonia-like shadow on chest roentgenogram].

A 67-year-old female was admitted to our hospital because of pneumonia-like shadow on chest roentgenogram with persistent cough and sputum of 4 months duration. Diagnosis as lung cancer was delayed more than 4 months. She showed fever and inflammatory reactions. Antibiotics were effective to inflammatory reactions, but not effective to pneumonia-like shadow. Transbronchial lung biopsy was useful for the diagnosis. Right lower lobectomy was performed. In this case, tumor extents were limited within one lobe. Tumor cells did not invade blood and lymphatic vessels, and extrathoracic metastases were not detected. The prognosis of bronchiolo-alveolar cell carcinoma was determined by intra-pulmonary tumor extent. Based on a comparison with the outcome of unresected cases, bronchiolo-alveolar cell carcinoma limited within one lobe should be surgically resected.

[Three resected cases of pulmonary cryptococcosis].

Case 1 was a 53-year-old female who had a small nodule in the right S3 segment on chest CT. As she was not diagnosed by transbronchial lung biopsy (TBLB), open thoracotomy was performed. Case 2 was a 65-year-old female who had a nodule with pleural indentation in the right S6 segment. As this nodule showed difficulty to differentiate from small lung carcinoma, thoracoscopic surgery was performed. Case 3 was a 63-year-old female who had multiple lesions with cavity in the left S4 and S5 segments, which was preoperatively diagnosed by TBLB. She was performed thoracoscopic partial resection of the lingular segment because of poor response to antimycotic agents. All cases received preventive antimycotic agents for one or two months after the operation. There was no recurrence or postoperative meningitis. Thoracoscopic surgery is the effective procedure for the diagnosis and treatment of the localized pulmonary cryptococcosis.

[Apolipoprotein E immunoreactivities in normal human ovary and ovarian neoplasms].

An immunohistochemical study on localization of apoE in normal human ovary and various ovarian neoplasms was performed using polyclonal anti-human apoE antibody. In the normal tissues, apoE immunoreactivity was found in folliculus (theca interna and stratum granulosum), and most intensely in a corpus luteum. The stroma cells were not stained. Among various ovarian tumours, positive staining was found in granulosa cell tumour, teratoma and dysgerminoma. Close relationship between apoE and steroid synthesis was suggested by the distribution of apoE in the studied tissues. The present results show that an immunohistochemical study for apoE may be helpful for the diagnosis of steroid producing tumours.

[Clinical analysis of lung cancer in patients with chondromatous hamartoma].

Between 1978 and 1993, 776 patients with lung cancer and 18 patients with chondromatous hamartoma were operated on in the department of Surgery II in Okayama University Hospital. 3 patients had both lung cancers and chondromatous hamartomas. They were all men. Two patients were 65 years old and the other was 82 years old. They all pointed out them by a medical examination of chest X-ray. 2 patients had lung cancers and chondromatous hamartomas in the same lobe, the other had them in other lobe of the same side. Lung cancer and chondromatous hamartoma localized in near area. It was difficult to discriminate chondromatous hamartoma between pulmonary metastasis of lung cancer before an operation.