IL-28B (IFN-λ3) and IFN-α synergistically inhibit HCV replication.

Genetic variation in the IL-28B (interleukin-28B; interferon lambda 3) region has been associated with sustained virological response (SVR) rates in patients with chronic hepatitis C treated with peginterferon-α and ribavirin. However, the mechanisms by which polymorphisms in the IL-28B gene region affect host antiviral responses are not well understood. Using the HCV 1b and 2a replicon system, we compared the effects of IFN-λs and IFN-α on HCV RNA replication. The anti-HCV effect of IFN-λ3 and IFN-α in combination was also assessed. Changes in gene expression induced by IFN-λ3 and IFN-α were compared using cDNA microarray analysis. IFN-λs at concentrations of 1 ng/mL or more exhibited concentration- and time-dependent HCV inhibition. In combination, IFN-λ3 and IFN-α had a synergistic anti-HCV effect; however, no synergistic enhancement was observed for interferon-stimulated response element (ISRE) activity or upregulation of interferon-stimulated genes (ISGs). With respect to the time course of ISG upregulation, the peak of IFN-λ3-induced gene expression occurred later and lasted longer than that induced by IFN-α. In addition, although the genes upregulated by IFN-α and IFN-λ3 were similar to microarray analysis, interferon-stimulated gene expression appeared early and was prolonged by combined administration of these two IFNs. In conclusion, IFN-α and IFN-λ3 in combination showed synergistic anti-HCV activity in vitro. Differences in time-dependent upregulation of these genes might contribute to the synergistic antiviral activity.

[Clinical effect of the cauterization for emphysematous bulla].

The purpose of performing pleural cauterization is developing heat denaturation, and we can induce pleural thickening and also reduce the bullae by shrinking the pleura It originates in a method of the cauterization whether there will be tissue damage. So a safe and reliable method of cauterization is required. Here, we investigated the indications for and effectiveness of cauterization techniques performed at our facility. We perform cauterization while dropping saline solution, so when using a Salient Monopolar Sealer, we can avoid excessive thermo-coagulation and more easily control cauterization. Furthermore, on the basis that only emphysematous pleura will turn white on cauterization, bullae can be distinguished, which is particularly effective in the case of lesions with unclear borders. In the case of a large emphysematous bulla, shrinkage of the bulla by cauterization can provide a sufficient surgical field, and a smaller lesion can then be stapled.

A surgical case of pulmonary adenocarcinoma complicated with pulmonary infarction presenting as an intrapulmonary metastasis.

Pulmonary adenocarcinoma complicated with a pulmonary infarction presenting as an intrapulmonary metastasis is relatively rare. We present a case of pulmonary infarction manifesting as intrapulmonary metastases of lung cancer. A previously healthy 59-year-old woman was admitted to our hospital on May 16, 2002 for evaluation of multiple abnormal radiographic shadows in the right lower lung field. Laboratory tests showed no abnormalities except for a slight elevation of carcinoembryonic antigens. Computed tomography of the chest revealed a hilar mass lesion with parenchymal lesions in the periphery of the right lower lobe, highly suspected to be a pulmonary adenocarcinoma with intrapulmonary metastases. A diagnosis of pulmonary adenocarcinoma was confirmed by a transbronchial brushing examination. A right middle and lower bilobectomy with mediastinal lymph node dissection was needed by hilum lymphadenopathy and a lower lobe invasion of the main tumor. Histopathological findings of the resected specimens revealed poorly differentiated adenocarcinoma of the lung with N1 (#11i) disease and multiple pulmonary infarctions with coagulation necrosis and recanalization. Pulmonary infarctions are demonstrated on chest x-rays as round or polygonal in shape, and located at the periphery of the same lobe as the primary tumor. Computed tomography is more sensitive than conventional radiography in the detection of pulmonary infarction. Our case suggests that pulmonary infarction associated with lung cancer should be considered as one important cause of peripheral pulmonary nodules.

[Chondrosarcoma of rib origin; report of a case].

Chondrosarcoma of rib origin is rare. A 50-year-old man without symptom was pointed out an abnormal shadow on chest X-ray. Computed tomography (CT) showed a low density mass arising from the right chest wall, and a CT-guided needle aspiration biopsy disclosed the tumor consisted of cartilage matrix with a partial necrosis. We suspected the tumor to be a chondrosarcoma of rib origin and performed a wide resection with the right 3rd and 4th ribs. The defect of the chest wall was repaired with double prolene mesh. Histological examination revealed grade 2 chondrosarcoma. Postoperative course has been uneventful for 25 months.

[Quality of life of long-term survivors of surgically treated lung cancer].

Quality of life (QOL) of long-term survivors (more than 3 years after surgery) of primary non-small cell lung cancer was studied. QOL was analyzed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, 30-Item version 3.0 (QLQ-C30) and Hospital Anxiety and Depression Scale (HADS). Sixty of 91 patients (66%) participated in this study 87 +/- 5 (38-172) months postoperatively. In QLQ-C30, calculated scores of physical (84.0 +/- 2.4), role (81.3 +/- 3.6), cognitive (79.7 +/- 2.6), emotional (86.8 +/- 1.9), and social (91.0 +/- 1.9) functioning, and global QOL (72.6 +/- 2.9) were obtained. Calculated HADS A (anxiety) was 3.3 +/- 0.3 and HADS D (depression) was 4.0 +/- 0.4. Postoperative follow-up duration was correlated with financial impact only. QOL of long-term survivors was influenced by gender histology, marital status, employment status, and academic carrier.

[Aneurysmal bone cyst arising in the rib; report of a case].

We experienced with a relatively rare case of an aneurysmal bone cyst (ABC) arising in the left rib. A 34-year-old female, had experienced chest discomfort on the left anterior side and pain for 1 year. A chest X-ray suggested a left chest wall tumor involving the ribs. Computed tomography (CT), magnetic resonance imaging (MRI) and a bone scintigram revealed an expansive tumor of the anterior portion of the left 4th rib involving the 3rd and 5th rib with "blow out appearance" and "fluid-fluid level". Wide excision of the tumor and adjacent muscle tissue was performed with an antero-axillary incision. Chest wall reconstruction was performed with prolene mesh (140 x 90 mm). The resected specimen showed an encapsulated bony mass (75 x 60 x 35 mm) with multiple blood-filled spaces. Histopathological diagnosis was an ABC originating in the left 4th rib. She has been doing well with no evidence of recurrence 12 months postoperatively.

Pathologic comparison of video-assisted thoracic surgical lung biopsy with traditional open lung biopsy.

Video-assisted thoracic surgical lung biopsy is an alternative to traditional open lung biopsy for diagnosis in patients with pleuropulmonary diseases. Between January 7, 1991, and August 3, 1993, 71 consecutive patients had video-assisted thoracic surgical lung biopsy and 42 patients had traditional open lung biopsy. A specific histologic diagnosis that correlated with the clinical findings was sought in each case and the yield was compared between the two groups. Procedure-related artifactual changes were also evaluated; the extent of traumatic hemorrhage and neutrophil margination as a result of tissue manipulation was significantly greater for patients in the video-assisted thoracic surgical lung biopsy group than for those in the open lung biopsy group, but the changes were generally minor and did not affect diagnostic yield. Complications developed in 11 (15%) of 71 patients in the video-assisted thoracic surgical lung biopsy group including 5 patients with prolonged air leakage (more than 10 days); 2 with pneumonia; and 1 each with bleeding, late pneumothorax necessitating readmission, mucus plug necessitating bronchoscopy, and a hypoxic episode necessitating mechanical ventilation. On the other hand, 7 (17%) of 42 patients in the open lung biopsy group had complications including 4 patients with prolonged air leakage (more than 10 days) and 3 with pneumonia. There were 6 (8%) operative deaths in patients who had video-assisted thoracic surgical lung biopsy and 7 (17%) in the open lung biopsy group; all had preoperative respiratory failure. We conclude that video-assisted thoracic surgical lung biopsy is an acceptable alternative to open lung biopsy for diagnosis of pulmonary infiltrates or indeterminate nodules.

Benign solitary fibrous tumor of the parietal pleura which invaded the intercostal muscle.

A 29-year-old woman who underwent evaluation for a 3-month history of left-sided back pain proved to have a left pleural tumor accompanied by a bloody pleural effusion (cytological class II). Three years previously, a chest roentgenogram had been normal. The tumor originated from the parietal pleura at the level of the first three intercostal muscles and was excised completely in continuity with these muscles, including a margin of normal muscle. The tumor measured 15x12 cm and the pathologic diagnosis was benign solitary fibrous tumor; while the tumor invaded the intercostal muscles, no histologically malignant features were present. Long-term follow-up is planned because a possibility of local recurrence exists.

Micronucleus test and erythropoiesis: effect of cobalt on the induction of micronuclei by mutagens.

The micronucleus test is used widely as an in vivo short-term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by cobalt dichloride pretreatment. Cobalt dichloride was used to induce erythropoietin, a growth factor for erythropoiesis. The increase in mutagen-induced micronucleus response following cobalt pretreatment, therefore, may have been due to a change in the rate of erythropoiesis. The greatest interaction between cobalt pretreatment and mutagen treatment for the induction of micronucleated polychromatic erythrocytes (MPCE) occurred when mice were injected with 1,1-dimethylhydrazine (DMH) 12-24 hr after pretreatment with cobalt dichloride and killed 30 hr later. Increased sensitivity of the micronucleus test was attributable to the administration of mutagen during the differentiation and multiplication of erythroblast, which is presumed to have been accelerated by pretreatment with cobalt dichloride. An increased induction of MPCE in the bone marrow by two chemicals--benzo(a)pyrene, 2-naphthylamine--was also observed following pretreatment with cobalt dichloride.

Effects of prostaglandin E2 on the micronucleus formation in mouse bone marrow cells by various mutagens.

The effects of prostaglandin E2 (PGE2), as a trigger of erythroid progenitor cells into the cell cycle, were studied on the induction of micronuclei by various mutagens; with mitomicin C (MMC) the optimal protocol was established. PGE2 itself did not induce any micronuclei in this experiment. The highest frequency of micronuclei and dose-response relationship between PGE2 doses and micronucleus frequency were observed 30 h after injection of MMC to mice administered PGE2 24 h previously. Sensitization by PGE2 pretreatment was also found for other mutagens, such as vincristine, 5-fluorouracil, benzo[a]pyrene, 1,1-dimethylhydrazine and 2-naphthylamine. These results support the hypothesis that accelerating the erythropoiesis increases the frequency of micronuclei induced by mutagens.

Post radiation inflammatory malignant fibrous histiocytoma arising from the chest wall.

A 59-year-old man who underwent radiation therapy (41 Gy) to the mediastinum through the anterior chest for Hodgkin's disease presented with a painful anterior chest wall tumor 18 years later. The tumor originated from the left parasternal region and was excised with the sternum. Chest wall reconstruction was performed. The tumor measured 45 x 45 mm and invaded the sternum. The pathologic diagnosis was malignant fibrous histiocytoma. Early and complete excision of the tumor is indicated.

Hyperacute xenorejection of guinea pig-to-rat lung transplantation can be attenuated by blood which has perfused another xenograft.

In discordant xenotransplantation, the recipientOs blood initiates hyperacute xenorejection (HXR). We hypothesized that HXR-related lung edema may be reduced if a new xenograft is perfused by blood which previously has perfused another xenograft. In a syngeneic control group (n = 6), a rat lung (lung XR) was perfused by rat blood (blood AR), following which the blood was collected (blood BR). After another rat lung (lung YR) was perfused by blood BR, the blood was collected (blood CR). In a xenogeneic experimental group (n = 6), a guinea pig lung (lung XG) was perfused by rat blood (blood AG), and the blood was collected (blood BG). Then, another guinea pig lung (lung YG) was perfused by blood BG, and once more the blood was collected (blood CG). White blood cells (WBC), polymorphonuclear leukocytes (PMN), red blood cells (RBC), hemoglobin, hematocrit, and complement (CH50) in the blood were measured pre- and post-perfusion. The wet/dry weight ratio (W/D) of the lung was calculated after the perfusion. WBC and PMN were higher in blood CR/BR than in blood BR/AR. CH50 was higher in blood CG/BG than in blood BG/AG. RBC, hemoglobin, and hematocrit were not different among the blood AR, BR, CR, AG, BG, and CG. The W/D was not different between lung XR and lung YR. The W/D of lung YG was lower than lung XG. In conclusion, the lung edema associated with HXR is reduced when blood which has perfused another xenograft is used to perfuse the new xenograft without anemia, and complement plays a critical role in reducing lung edema.

Five cases of asymptomatic spontaneous pneumothorax.

Asymptomatic spontaneous pneumothorax (ASPT) is an uncommon condition. Between January 1, 1989 and December 31, 1997, 269 patients were admitted to our department with spontaneous pneumothorax. Of the 269 patients, 5 had no symptoms at the time of discovery. Their ages ranged from 15 to 61 years (mean, 37.8 years), and all of them were male. Of the 5 patients with no complaints, 2 had bilateral metachronous pneumothoraces and 3 had hemilateral pneumothorax. All of these ASPTs were revealed by chest roentgenographs taken during medical examinations or follow-up studies relating to other diseases. The mean value of body mass index (BMI) was 19.96 +/- 1.4 (range 18.7 - 22.1). Two of the 5 patients underwent bilateral partial lung resection. Histopathological examination of the resected specimens showed elastofibrosis, scar formation, and an interruption of the elastic fiber of the pleura. In these 5 cases, clinical courses were uneventful, and relapse of the pneumothorax did not occur. Clinical physicians should be aware of the possibility of asymptomatic pneumothorax, as well as the optimal radiographic techniques for revealing small pneumothoraces.

[A basic study for estimating the level of exposure to a nasal inhalant containing a stimulant].

Criminal cases involving stimulant abuse have increased since 1970 but have now leveled off. Some of the offenders claimed to have used the Vicks Inhaler containing a stimulant (1-methamphetamine) which is used for the treatment of nasal obstruction. The aim of this experiment was to measure the amount of 1-methamphetamine contained in the Vicks Inhaler by stimulating the human respiratory system. The results are as follows: 1) The data from the stimulation experiment showed that the inhalation level of 1-methamphetamine was estimated to be 320.4ng. From this value, the level of 1-methamphetamine absorbed per one respiration was calculated to be 21ng. 2) The data from quantitative and qualitative analysis by gas-chromatography showed that menthol interfered with the methamphetamine. 3) A qualitative test for the stimulant in urine was negative when the subject inhaled the Vicks Inhaler only once. However, this test turned positive when the subject inhaled it more than 17 times.

[Job stressors in software developers--a comparison with other occupations].

The aim of this study is to investigate the difference in job stressors among software developers, the sales staff and the clerical staff (n = 2,079) in two companies (A Co. and B Co.) using a self-administered questionnaire that included a job stressor scale and the 30-item General Health Questionnaire (GHQ). We developed the job stressor scale based on the interviews with out-patients who engaged in software development and previous studies about job stressors. Factor analysis with a seven-factor solution showed that seven subscales were abstracted from the job stressor scale, namely, quantitative load of work, dissatisfaction with work, demanding work, uneasiness about work, human relations, ambiguity of work and shortage of private time. Each subscale was significantly (r = .313-.442, p < 0.0001) correlated with the GHQ score and proved to be a reliable instrument, as indicated by a Cronbach's alpha of greater than 0.73. Stepwise multiple regression analysis revealed that quantitative load of work and shortage of private time subscale scores were significantly high in software developers in A Co. Software developers in A Co. tended to score higher (P < .10) than the others in demanding work and ambiguity of work subscale. All subscale scores were significantly low in the clerical staff in B Co. There was no significant difference between the sales staff and software developers in B Co. Results of the interviews with out-patients showed that demanding work, hard deadline, ambiguity of work and precarious work would cause trouble in software developers. The implications of these findings with respect to occupational issues related to software developers are discussed.

[Experience with invasive thymoma presenting pleural dissemination].

A 61-year-old man was admitted to Showa University Hospital because of a myasthenia gravis. Chest computed tomography revealed a mediastinal invasive tumor. During surgery, invasion to the pericardium and dissemination on the left visceral pleura and the left diaphragm were observed. Extended thymo-thymectomy and partial resection of the pericardium, left lung, and diaphragm were performed. Incomplete resection was achieved because of the dissemination on the diaphragm. Chemotherapy using ADOC and radiotherapy for mediastinum and left diaphragm were done. Four years after surgery, neither recurrence of the tumor nor myasthenia gravis was observed.

[A surgical case of giant mediastinal teratoma].

A 35-year-old female was admitted with a large abnormal shadow in the left lung field on a chest X-ray. She was examined by chest tomogram, chest CT, MRI and bronchofiberscope. The CT and MRI showed a large tumor mass pressing the left lung and calcified deposits in the central part of the tumor. Bronchofiberscopic findings showed a stenosis of the left main bronchus. The clinical diagnosis was mature teratoma arising from anterior medistinum. She underwent a median sternotomy and the tumor was removed. The size of the resected specimen, filled with sebaceous material, hair and teeth, etc., was 14 x 12 x 10 cm (1,045 g). Histopathological examination of the specimen revealed a mediastinal mature teratoma. She has been well for 16 months postoperatively.

[Postoperative temporal elevation of tumor marker in primary lung cancer patients].

Serum tumor marker measurement in addition to radiological examination is useful to detect postoperative recurrence and metastasis. Surgically treated 8 primary non-small cell lung cancer patients who showed negative serum tumor marker postoperatively elevated their markers temporally. Five of the 8 patients did not show recurrence or metastasis in their last confirmation days. These 5 patients had inflammatory disease when the postoperative marker became positive temporally. Remaining 3 patients did not have inflammatory disease when the marker elevated temporally. The marker of the 3 patients became negative again, however, the 3 patients showed recurrence or metastasis during 1 year after temporally elevated day. In conclusion, if there is no inflammatory disease when the negative marker becomes positive temporally, the recurrence or metastasis may be observed during 1 year after temporally elevated day. And when the recurrence or metastasis is observed radiologically, the marker may become negative.

[A surgically treated case of capsulated thymoma with thymic cyst].

A 56-year-old woman was pointed out an abnormal shadow on chest roentgenogram. Chest CT and MRI showed a solid mass with a cyst at right anterior mediastinum. Clinical diagnosis was thymoma with cyst, and surgical excision was performed. The histopathological examination of the resected specimen demonstrated that the epithelia of the cyst wall was single cuboidal or squamous cells and contained some foci of thymic tissue. The solid mass was capsulated and predominantly composed of lymphocytes. The pathological diagnosis was a thymoma (predominantly lymphocytic type) with thymic cyst. She is doing well for 10 years postoperatively.

[Surgically treated pancoast tumor].

A 40-year-old male was detected his right apical lung tumor by roentgenographic screening on January 1997, but he did not refer to a hospital since he had no symptom. He went a orthopedics because of his right chest, back, and arm pain on October 1997, and he received traction and physical therapy. He went roentgenographic screening again on January 1998 and he was pointed out that the tumor increased. He admitted our hospital. Biopsy using bronchofiberscopy revealed adenocarcinoma and induction radiotherapy (40 Gy) was performed. Right upper lobectomy with chest wall resection and lymph node dissection was performed under hook approach. This approach was useful to dissect the tumor from the invaded plexus brachialis. Postoperative radio-chemotherapy was added but the patient died 7-postoperative months because of multiple metastases. Early detection should be led to early starting of the therapy.