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AimsMalignant pleural mesothelioma with heterologous elements (such as osseous, cartilaginous or rhabdomyoblastic differentiation) is very rare. We tried to differentiate such mesothelioma cases from extraskeletal pleural osteosarcoma, which is very challenging.MethodsWe compared 10 malignant pleural mesotheliomas (three biphasic and seven sarcomatoid types) with two pleural osteosarcomas using clinicopathological and immunohistochemical methods, and also fluorescence in situ hybridisation (FISH) to examine for homozygous deletion of p16.ResultsThe median age was 72 years for mesotheliomas, and 69 years for osteosarcoma. For mesothelioma, eight cases were male and two were female. Growth was diffuse in all mesothelioma cases except case 10, where it was localised, as it was for the two osteosarcomas. Among mesothelioma cases, 80% displayed osteosarcomatous and 60% chondromatous elements, while 10% exhibited rhabdomyoblastic ones. Immunohistochemical labelling for calretinin and AE1/AE3 was present in 8/10 and 7/10 mesotheliomas, respectively, but in only one osteosarcoma. Loss of methylthioadenosine phosphorylase was seen in 5/7 mesotheliomas. FISH analysis revealed homozygous deletion of p16 in 5/8 mesothelioma and 2/2 osteosarcoma. Median survival was 6.5 months after biopsy or surgical operation in mesothelioma, and 12 months after operation in osteosarcoma.ConclusionsAlthough median survival was longer for osteosarcoma than for malignant mesothelioma, we could not differentiate mesothelioma from pleural osteosarcoma on the combined basis of clinicopathological and immunohistochemical data, and FISH analysis. However, diffuse growth was more frequent in mesothelioma than in osteosarcoma.

Rapid economic growth and a changing disease burden have increased the demand for pathology services in Cambodia. This paper describes the status of pathological services and international support for pathology professionals in Cambodia, and discusses future needs for strengthening pathology services. In 2016, there were only four pathologists and 18 pathology technologists in Cambodia. A postgraduate course in pathology was created in 2015, and five residents became certified in 2018. Besides multinational support with lectures and practice for pathologists, the Japanese team provides on-the-job training for pathology technologists to improve slide preparation for diagnosis. A clinicopathological conference was introduced to strengthen the communication among pathologists, pathology technologists, and gynecologists. Although there is a long way to go to reach high quality pathological services, coordination among international partners needs to continue, as does the balance between human resource development for pathology professionals, to provide a higher level of care to local citizens.

This study assesses the effects of sending home energy reports utilizing the Home Energy Management System (HEMS) data to more than 1600 households in Japan. The treatment effect was verified using a panel data regression random effects model comparing the electricity consumption of a treatment group to which the report was sent with that of a control group that was not sent. The report was effective in winter and led to a 3.4% reduction in electricity consumption compared to the previous year in the average household. A further reduction of 5.4% for the households with higher electricity consumption for whom a significant reduction of 11.4% in the use of space heating was also observed. Although the treatment effect was not significant in summer for the average household, larger households reduced consumption by an overall average of 2%, with reductions of 6.8% and 7% in terms of space cooling and hot water use, respectively, from the previous month. In contrast, smaller households increased their space cooling consumption by more than 10% on average, which might be considered an undesirable boomerang effect. The accumulative treatment effect in a detached house group was also confirmed. Additionally, an accumulative two-year winter consumption reduction of 7.5% demonstrated the effectiveness of continual intervention.

Deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. Malignant rhabdoid tumors, renal medullary carcinoma, and some synovial sarcomas show a loss of SMARCB1/INI1 protein, a member of the SWI/SNF chromatin-remodeling complex. All of those tumors are known to have rhabdoid cells. Some mesothelioma cases, such as those of the deciduoid type, have also been reported to possess such rhabdoid features. Since this topic has not been studied in malignant mesothelioma, we analyzed the immunohistochemical expression of SMARCB1/INI1 in malignant mesotheliomas [45 epithelioid type (including 9 deciduoid type), 12 biphasic type, and 17 sarcomatoid type]. We employed (a) SMARCB1/INI1 immunohistochemistry, using an antibody to the INI1 gene product and (b) Fisher exact test, logistic regression analysis, the Kaplan-Meier method, and the Wilcoxon test for survival analysis for prognostic factor evaluation (SAS 9.4; SAS Institute, Cary, NC). The results showed that 17 of 74 (23%) malignant mesothelioma cases (epithelioid: 24%; biphasic; 8%; sarcomatoid; 29%) had reduced SMARCB1/INI1 expression. Reduced SMARCB1/INI1 expression appeared to be more frequent in the deciduoid type (67%), of which there were admittedly only a few cases, than in either the epithelioid type (14%) or biphasic type (8%), whether or not rhabdoid cells were present, but not different between the deciduoid and sarcomatoid types. However, there was no statistically significant difference in prognosis between malignant mesotheliomas with reduced versus preserved SMARCB1/INI1 protein expression. The results suggest that in differential diagnosis, cases with reduced SMARCB1/INI1 protein expression should not be excluded from a diagnosis of malignant mesothelioma.

Aims Peritoneal malignant mesothelioma (PMM) is an uncommon tumour, accounting for only 7–9% of all mesotheliomas in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging. Methods To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine mesothelial-associated markers (calretinin, AE1/AE3, CK5/6, CAM5.2, D2-40, WT-1, HBME1, thrombomodulin), adenocarcinoma-associated markers (CEA, BerEP4, MOC31, ER (estrogen receptor), PgR, TTF-1, Claudin-4, Pax8), and malignant-related and benign-related markers (epithelial membrane antigen (EMA), desmin, GLUT-1, CD146 and IMP3), and FISH to examine for homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 22 PMMs (M:F=18:4; subtypes: 16 epithelioid, 6 biphasic), 11 PPSCs and 23 RMHs. Results Seventeen of the mesotheliomas (four PMM from women) were classified as diffuse, while five were localised. Calretinin was 91% positive in PMM, but negative in PPSC (specificity, 100%). BerEP4, Claudin-4 and PAX8 were all 100% positive in PPSC (specificities, 100%, 95% and 95%, respectively, for excluding PMM). For distinguishing PMM and RMH, sensitivity for EMA in mesothelioma was 68%, while for IMP3 and GLUT-1 it was 64% and 50%, respectively, all with high specificities. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/13 PMMs, but in 0/11 RMHs. Conclusions Calretinin and BerEP4 may be the best positive markers for differentiating PMM from PPSC. EMA, in combination with IMP3 and desmin, is useful, and homozygous deletion of 9p21 may be helpful, for differentiating PMM from RMH.

Background: The introduction of new therapies has made it important to differentiate between adenocarcinoma and squamous cell carcinoma. To allow the use of various immunocytochemical stains on limited materials, we tried transferring cells from a given smear to multiple slides. Using touch-preparation samples of 215 surgically resected non-small cell lung carcinomas of confirmed histologic classification (adenocarcinoma,n = 101; squamous cell carcinoma,n = 114), we performed immunocytochemistry for thyroid transcription factor-1, napsin A, p40, p63, CK5/6 and desmocollin-3, and compared cytologic staining results with the corresponding resection. Methods: We examined: (a) the expressions of the above 6 antibodies on cells transferred from touch imprints of resected specimens, the extent of staining being considered positive if more than 5% of the area was stained, and (b) the sensitivity, specificity, positive predictive value and negative predictive value for each antibody. Results: The histologic corresponding rate with Papanicolaou staining was only 73%. Regarding the differentiation of adenocarcinoma from squamous cell carcinoma, the sensitivity and specificity for napsin A in adenocarcinoma were 80 and 97%, respectively, while those for p40 in squamous cell carcinoma were 84 and 98%, respectively. Conclusion: The immunocytochemical expressions of napsin A and p40 in imprint cytology seem to be of great utility for the accurate histological differentiation of lung cancers.

The electrorheological (ER) effect and the electro-optical properties of a ''side-on'' liquid crystalline polysiloxane (PS) are investigated. A large ER effect is observed and the response to the shear stress of neat PS in the nematic phase is shown to be affected by the shear rate. PS is also mixed with a low-molar nematic liquid crystal (5CB) in order to improve the response behavior to the applied electric field. The rheological properties of such mixtures are highly dependent on the concentration of 5CB. The composites respond faster to the applied electric field and have improved electro-optical properties. This study offers a new perspective on the development of liquid crystal materials for the ER effect.

We report a very unusual cytologic feature, intranuclear inclusion bodies, in mesothelioma of a predominantly adenomatoid type. The patient, a 57-year-old woman, was presented with dyspnea and right pleural effusion. Pleural aspiration cytology revealed many cohesive ball-like clusters, with a tubular pattern, composed of small atypical cells displaying a high-nuclear-cytoplasmic ratio. They had a nuclear groove and irregular intranuclear inclusion bodies. Right lung partial resection with thoracoscopy revealed that a white tumor had proliferated along the pleural surface at S(8) . Histology revealed nodular tumor cells forming dilated structures mixed with small tubular or glandular structures similar to those seen in benign adenomatoid tumors. These tumor cells had invaded peripheral lung tissues. Such inclusion bodies have not been reported earlier in mesothelioma. On the basis of this observation, we propose that the adenomatoid type of malignant mesothelioma be added to the differential diagnosis of malignant effusions when tumor cells with nuclear grooves and intranuclear inclusions are found in pleural aspiration cytology.

Sarcoidosis is a systemic granulomatous inflammation of unknown etiology, and seems to involve the liver parenchyma in most cases. However, sarcoidosis-associated hepatocellular carcinoma is rare. We report here a case in which a hepatocellular carcinoma occurred within the liver, which was probably involved as a result of systemic sarcoidosis. A 57-year-old Japanese man had been followed up for 2 years because of diabetic nephropathy and sarcoidosis. On admission for pneumonia, imaging studies revealed an unexpected hepatic tumor. Histology revealed a hepatocellular carcinoma accompanied by T-lymphocytic infiltration and marked granulomatous inflammation, which was surrounding some tumor nodules. The background liver parenchyma exhibited a moderate degree of fibrosis with granulomatous inflammation. The patient had no other apparent liver disease such as viral hepatitis, steatohepatitis, or primary biliary cirrhosis. Therefore, in the present case, sarcoidosis may be considered the probable background etiology for hepatocarcinogenesis.

OBJECTIVE To examine glucose-regulated protein 78 (GRP78; a major molecular chaperone at the endoplasmic reticulum, strongly expressed in several tumours) expression in urothelial carcinoma (UC) of the upper urinary tract (UUT) and to evaluate the diagnostic and progressive importance of GRP78 expression in UC-UUT. PATIENTS AND METHODS We investigated GRP78 expression (using immunohistochemistry) in 126 UC-UUTs to assess its relevance to progression. GRP78 overexpression was recognised in 23 (18.3%) of tumour samples. RESULTS There was no association between GRP78 overexpression and clinicopathological findings, except for an association with low grade in invasive tumours. GRP78 overexpression significantly improved the disease-free survival rate in all patients (according to univariate and multivariate analyses), but did not alter the overall survival rate. CONCLUSION The detection of GRP78 overexpression would appear to provide valuable information for the prognosis of UC-UUT.

Lymphohistiocytoid mesothelioma (LHM), reported to be a rare variant of sarcomatoid mesothelioma, is challenging to differentiate from non-Hodgkin's lymphoma due to marked lymphocytic infiltration. To aid accurate recognition of LHM, we examined immunohistochemical, in situ hybridization (ISH) of Epstein-Barr virus RNA (EBER-1) mRNA, fluorescence ISH (FISH) for homozygous deletion of 9p21, and asbestos analysis in four cases (three men and 1 woman). Three patients died, while Case 4 was still alive 19 months after extrapleural pneumonectomy. Histologically, these cases were characterized by heavy lymphocytic infiltration. All neoplastic cells were positive for calretinin, AE1/AE3, and epithelial membrane antigen, but negative for CEA. EBER1 factor was negative. FISH analysis demonstrated homozygous deletion of the 9p21 locus in three of the four cases. In Case 1: (i) autopsy findings showed mesothelioma primarily located in the right parietal pleura, but metastasized into the left lung and abdominal organs; (ii) the histological findings at autopsy indicated sarcomatoid mesothelioma; and (iii) we found asbestos bodies and fibers in extracts from lung tissue (Cases 1 & 4) using digestion with bleaching fluid. LHM, an infrequent variant of sarcomatoid mesothelioma, displayed homozygous deletion of the 9p21 locus (three of four cases), and has a relatively favorable prognosis for the sarcomatoid type.

An energy-discrimination K-edge X-ray computed tomography (CT) system is useful for increasing the contrast resolution of a target region by utilizing contrast media. The CT system has a cadmium telluride (CdTe) detector, and a projection curve is obtained by linear scanning with use of the CdTe detector in conjunction with an X-stage. An object is rotated by a rotation step angle with use of a turntable between the linear scans. Thus, CT is carried out by repetition of the linear scanning and the rotation of an object. Penetrating X-ray photons from the object are detected by the CdTe detector, and event signals of X-ray photons are produced with use of charge-sensitive and shaping amplifiers. Both the photon energy and the energy width are selected by use of a multi-channel analyzer, and the number of photons is counted by a counter card. For performing energy discrimination, a low-dose-rate X-ray generator for photon counting was developed; the maximum tube voltage and the minimum tube current were 110 kV and 1.0 microA, respectively. In energy-discrimination CT, the tube voltage and the current were 60 kV and 20.0 microA, respectively, and the X-ray intensity was 0.735 microGy/s at 1.0 m from the source and with a tube voltage of 60 kV. Demonstration of enhanced iodine K-edge X-ray CT was carried out by selection of photons with energies just beyond the iodine K-edge energy of 33.2 keV.

Melanoma metastasizing to the lungs is common, but primary pulmonary or pleural melanoma is extremely rare. We present an autopsy case of malignant melanoma of the pleura without primary skin lesion in a 49-year-old man. A mass found in the right chest was diagnosed as spindle cell sarcoma by antemortem fine-needle aspiration cytology. At autopsy, a yellow-white tumor located primarily in the right visceral pleura (diagnosed as an amelanotic melanoma) was found to have invaded into the right lung, right parietal pleura, and right diaphragm, and to have metastasized into the left lung and visceral pleura, thyroid, and left adrenal gland. No primary site was found. The tumor cells were positive for S100 and focally positive for HMB-45, but negative for other markers. Immuno-histochemical examination for S100 and HMB-45 would thus appear to be useful for the diagnosis of an amelanotic melanoma.

The earliest pathological events in the development of malignant pleural mesothelioma (MPM) are not understood. The aim of the present study was to elucidate the early histopathological features of MPM. A total of 16 extrapleural MPM pneumonectomy patients were investigated. Early stage mesothelioma was arbitrarily defined as a tumor < or =5 mm in thickness regardless of the nodal status or other organ involvement. Eight of these patients (six with epithelioid, two with biphasic) had early stage mesothelioma by this definition. Macroscopically there was no visible tumor, but the parietal and visceral pleura were thickened and there was focal adhesion between them. Microscopically, the mesothelioma lesions were multifocal and discontinuous on the pleura. In extremely early cases of epithelioid mesothelioma, tumor cells were generally arrayed in a single layer, but papillary proliferation was observed elsewhere. In sarcomatoid mesothelioma, mesothelioma cells proliferated, forming multiple small polypoid nodules on the pleura. Epithelial membrane antigen was helpful to distinguish reactive from neoplastic mesothelium, but glucose transporter-1 was not. Mesothelioma cells disseminate diffusely throughout the parietal and visceral pleura and mediastinal fat tissue before becoming visible. Stage Ia mesothelioma (neoplasm limited to the parietal pleura) would not be observed in daily practice.

Currently, it is difficult to carry out refraction-contrast radiography by using a conventional X-ray generator. Thus, we developed an embossed radiography system utilizing dual-energy subtraction for decreasing the absorption contrast in unnecessary regions, and the contrast resolution of a target region was increased by use of image-shifting subtraction and a linear-contrast system in a flat panel detector (FPD). The X-ray generator had a 100-microm-focus tube. Energy subtraction was performed at tube voltages of 45 and 65 kV, a tube current of 0.50 mA, and an X-ray exposure time of 5.0 s. A 1.0-mm-thick aluminum filter was used for absorbing low-photon-energy bremsstrahlung X-rays. Embossed radiography was achieved with cohesion imaging by use of the FPD with pixel sizes of 48 x 48 microm, and the shifting dimension of an object in the horizontal direction ranged from 100 to 200 microm. At a shifting distance of 100 mum, the spatial resolutions in the horizontal and vertical directions measured with a lead test chart were both 83 microm. In embossed radiography of non-living animals, we obtained high-contrast embossed images of fine bones, gadolinium oxide particles in the kidney, and coronary arteries approximately 100 microm in diameter.

Background: The serum levels of soluble elastin increase in patients with aortic dissection, but its distribution and characteristics are unclear. Methods and Results: The 173 aortic specimens were categorized into 4 groups under microscopy (non-atherosclerotic aorta, n=13; fiber-rich plaque, n=77; lipid-rich plaque, n=66; ruptured plaque, n=17). Soluble elastin was abundant within the intima of both the non-atherosclerotic aorta and fiber-rich plaque, rather than in the media, and was decreased within the intima of lipid-rich and ruptured plaques. Soluble elastin levels decreased with progress of atherosclerosis (6.0 ±0.3 μg/mg protein in non-atherosclerotic aorta; 5.8 ±0.2 μg/mg protein in fiber-rich plaque; 4.9 ±0.2 μg/mg protein in lipid-rich plaque; 2.8 ±0.4 μg/mg protein in ruptured plaque, P

Peripheral nerve injury occasionally causes chronic neuropathic pain with hyperalgesia and allodynia. However, its treatment is difficult. Here, we used a chronic constriction injury (CCI) model in rats to investigate the effects on experimental neuropathic pain of the human hepatocyte growth factor (HGF) gene delivered into the nervous system by retrograde axonal transport following its repeated intramuscular transfer, using liposomes containing the hemagglutinating virus of Japan (HVJ). CCI (control) rats exhibited marked mechanical allodynia and thermal hyperalgesia, and decreased blood flow in sciatic nerve and hind paw. All these changes were significantly reversed by HGF gene transfer. In the sciatic nerve in HGF-treated rats, the size-frequency distributions for myelinated and unmyelinated axons each showed a rightward shift, the number of myelinated axons5 microm in diameter was significantly increased, and the mean diameter of unmyelinated axons was significantly increased (versus CCI rats). Levels of P2X3, P2X4, and P2Y1 receptor mRNAs, and of interleukin-6 (IL-6) and activating transcription factor 3 (ATF3) mRNAs, were elevated in the ipsilateral dorsal root ganglia and/or sciatic nerve by CCI, and these levels were decreased by HGF gene transfer. These results may point toward a potential new treatment strategy for chronic neuropathic pain in this model.

Background/Aims: Many studies report the role of vascular endothelial growth factor (VEGF) in wound healing, but few describe local VEGF administration to the digestive tract. Leakage from colonic anastomoses, including those due to ischemia, represents a major complication causing increased mortality and morbidity. Angiogenesis is crucial to anastomotic healing and restoration of blood supply, and VEGF is a potent angiogenic factor showing improved healing in various models of reconstruction and anastomosis. Here, we examine the effects of local VEGF-A165 administration on postoperative rabbit colon anastomosis. Methods: Two colotomies per animal were made in the sinistral colon on opposite sides of the mesentery. Randomly assigned VEGF (10 μg/0.1 ml) or saline (0.1 ml) was injected into the muscularis propria on both sides of each colonic anastomosis before closing the access laparotomy using single-layer sutures. On postoperative days 3, 4 and 7, the bursting pressure of partially healed anastomoses was measured. On postoperative day 4, anastomotic tissues were examined for the following: hydroxyproline; histopathologically for inflammatory infiltrate and tissue organization and immunohistochemically for capillary proliferation and density; vessel density of midzone collaterals around anastomoses by microangiography. Results: Compared to saline, VEGF administration significantly improved bursting pressure (p = 0.014, paired t test) and increased hydroxyproline (p = 0.027, paired t test) on postoperative day 4. Inflammatory cell infiltration and fibroblast proliferation were prominent, and submucosal capillary vascular counts were significantly higher for VEGF. Conclusions: Administration of VEGF to colonic anastomosis accelerates wound healing and strengthens the anastomosis by increased angiogenesis.

The contacts between epithelial cells are maintained mainly by adherens junctions and tight junctions (TJs). However, the role of TJ proteins in cancer is not well understood. We studied the expression of occludin and 4 claudins to assess their importance in the progression of urothelial carcinoma of the upper urinary tract (UC-UUT). In 129 cases, we examined their expression using immunohistochemical analysis and also their relationships to clinicopathologic parameters and clinical outcome. Positive expression of occludin and claudins 1, 3, 4, and 7 were recognized in 117 (90.7%), 113 (87.6%), 95 (73.6%), 127 (98.4%), and 123 (95.3%) of tumor samples, respectively. Claudin-3 expression was significantly associated with stage, grade, and pattern of growth. Claudins 1 and 4 expression was significantly associated with stage. However, neither occludin nor claudin-7 expression was associated with clinicopathologic findings. When tumors with scores below the median for a given protein were classified as the "low expression group," univariate analysis of overall survival revealed that claudins 1 and 3 had a significant effect on overall survival. Detection of claudins 1, 3, and 4 would seem to provide valuable information about the progression of UC-UUT.

A microfocus X-ray tube is useful for performing magnification digital radiography. The 100-µm-focus X-ray generator consists of a main controller, for regulating tube voltage and current, and a tube unit with a high-voltage circuit and a fixed anode X-ray tube. The maximum tube voltage, current, and electric power were 106 kV, 0.5 mA, and 50 W, respectively. Using a 100-µm-thick tungsten filter, the X-ray intensity was 19.8 µGy/s at 1.0 m from the source with a tube voltage of 100 kV and a current of 0.50 mA. Since Kα rays from tungsten targets are absorbed effectively by gadolinium-based contrast media, these rays are useful for performing enhanced angiography. Magnification angiography was performed by threefold magnification imaging using a computed radiography system and the filter at a tube voltage of 100 kV. In angiography of nonliving animals, we observed fine blood vessels of approximately 100 µm with high contrasts.

Resting cardiac function is a poor indicator of functional cardiac reserve that is invoked during exercise. The objective of this study was to investigate the relationship between functional cardiac reserve and systemic vascular resistance (SVR) using an ambulatory radionuclide monitoring system (the Vest system) in patients with heart disease. The study population consisted of 29 patients (all male [mean ± SD age, 63 ± 10 years]), 23 with coronary artery disease, 3 with dilated cardiomyopathy, and 3 with hypertensive heart disease. All patients underwent cardiopulmonary stress testing using a ramped treadmill protocol and the Vest system. The anaerobic threshold (AT) was autodetermined using the V-slope method. Systemic vascular resistance was calculated using the mean blood pressure and cardiac output as determined using the Vest system parameters. All patients exercised beyond the AT until exhaustion. Resting left ventricular ejection fraction, peak ejection ratio, and peak filling ratio increased with the AT (P < .01 for all). Resting SVR decreased with the AT (P < .01). The percentage changes from rest to the AT in SVR correlated with those from rest to the AT in ejection fraction, peak ejection ratio, and peak filling ratio (r = −0.735, r = −0.510, and r = −0.697, respectively; P < .01). These findings indicate that SVR as recorded using the Vest system is a good determinant of functional cardiac reserve in patients with heart disease. Therefore, cardiopulmonary function testing combined with the Vest system is a good modality for the evaluation of functional cardiac reserve.

A simple x-ray computed tomography(CT) system utilizing a cadmium telluride detector is described. The CT system is of the first generation type and consists of an x-ray generator, a turn table, a translation table, a motor drive unit, a cadmium telluride detector, an interface unit for the detector, and a personal computer(PC). Tomography was performed by the repetition of the translation and rotation of an object. The maximum values of the tube voltage and the tube current were 110kV and 2.0mA, respectively. Tomography was performed at a tube voltage of 60kV and a current of 1.5mA.

The construction of a photon-counting x-ray computed tomography(CT) system utilizing a cadmium telluride(CdTe) detector is described. The CT system is of the first generation type and consists of an x-ray generator, a turn table, a translation table, a motor drive unit, a CdTe detector, two amplifiers, multi-channel analyzer(MCA), and a personal computer(PC). Tomography was performed by the repetition of the translation and rotation of an object. Penetrating x-ray spectra from an object are measured by a spectrometer utilizing a CdTe detector and a MCA, and both the photon energy and the energy width are determined by the MCA.

Objectives: It can be difficult to differentiate diffuse malignant peritoneal mesothelioma (DMPM) from reactive mesothelial hyperplasia (RMH) or peritoneal dissemination of gynecologic malignancies, such as epithelial ovarian cancer (EOC), which cause a large amount of ascites. Detection of the homozygous deletion of p16/CDKN2A (p16) by fluorescence in situ hybridization (FISH) is an effective adjunct in the diagnosis of malignant pleural mesothelioma. The aim of this study was to investigate the ability of the p16 FISH assay to differentiate DMPM from RMH and EOC. Methods: p16 FISH was performed in 28 DMPMs (successful in 19), 30 RMHs, and 40 EOC cases. The cutoff values of p16 FISH were more than 10% for homozygous deletion and more than 40% for heterozygous deletion. Results: According to the above criteria, nine (47.4%) of 19 successful DMPM cases were homozygous deletion positive, and three (15.8%) of 19 were heterozygous deletion positive, whereas all RMH cases were negative for the p16 deletion. In all four major histologic subtypes of EOC, neither p16 homozygous nor heterozygous deletions were detected. To differentiate DMPM from RMH or EOC, the sensitivity of the p16 homozygous deletion was 32% (9/28), and the specificity was 100%. Conclusions: Our study suggests that p16 FISH analysis is useful in differentiating DMPM from RMH and EOC when homozygous deletion is detected.

The x-ray generator consists of the following components : a constant high-voltage power supply, a filament power supply, a turbomolecular pump, and an x-ray tube. The x-ray tube is a demountable diode which is connected to the turbomolecular pump and consists of the following major devices : a tungsten hairpin cathode (filament), a focusing electrode, a polyethylene terephthalate x-ray window 0.25mm in thickness, a stainless-steel tube body, and a rod target. In the x-ray tube, the positive high voltage is applied to the anode (target) electrode, and the cathode is connected to the tube body (ground potential). In this experiment, the tube voltage applied was from 12 to 18kV, and the tube current was regulated to within 0.10mA by the filament temperature. The electron beams from the cathode are converged to the target by the focusing electrode, and x-rays are produced from the target plane. The x-ray spectra were measured from two directions with angles between the electron trajectory and the x-ray beam axis of 180° and 90°. As compared with the x-ray spectra with an angle of 90°, the bremsstrahlung x-ray intensity decreased slightly with an angle of 180° (opposite direction to that of electron trajectory).

The 100-μm-focus x-ray generator consists of a main controller for regulating the tube voltage and current and a tube unit with a high-voltage circuit and a fixed anode x-ray tube. The maximum tube voltage, current, and electric power were 105kV, 0.5mA, and 50W, respectively. Using a 3-mm-thick aluminum filter, the x-ray intensity was 26.0μGy/s at 1.0m from the source with a tube voltage of 60kV and a current of 0.50 mA. Because the peak photon energy was approximately 35keV using the filter with a tube voltage of 60kV, the bremsstrahlung x-rays were absorbed effectively by iodine-based contrast media with an iodine K-edge of 33.2keV. Enhanced angiography was achieved with a flat panel detector with a pixel size of 50μm using iodine-based microspheres 15μm in diameter. In angiography of non-living animals, we observed fine blood vessels of approximately 100gm with high contrasts.

A preliminary experiment for producing narrow-photon-energy cone-beam X-rays using a silicon single crystal is described. In order to produce low-photon-energy X-rays, a 100-μm-focus X-ray generator in conjunction with a (1 1 1) plane silicon crystal is employed. The X-ray generator consists of a main controller and a unit with a high-voltage circuit and a microfocus X-ray tube. The maximum tube voltage and current were 35 kV and 0.50 mA, respectively, and the X-ray intensity of the microfocus generator was 48.3 μGy/s at 1.0 m from the source with a tube voltage of 30 kV and a current of 0.50 mA. The effective photon energy is determined by Bragg's angle, and the photon-energy width is regulated by the angle delta. Using this generator in conjunction with a computed radiography system, quasi-monochromatic radiography was performed using a cone beam with an effective energy of approximately 17 keV.

The tungsten plasma flash X-ray generator is useful in order to perform high-speed enhanced K-edge angiography using cone beams because K-series characteristic X-rays from the tungsten target are absorbed effectively by gadolinium-based contrast media. In the flash X-ray generator, a 150 nF condenser is charged up to 80 kV by a power supply, and flash X-rays are produced by the discharging. The X-ray tube is a demountable diode, and the turbomolecular pump evacuates air from the tube with a pressure of approximately 1 mPa. Since the electric circuit of the high-voltage pulse generator employs a cable transmission line, the high-voltage pulse generator produces twice the potential of the condenser charging voltage. At a charging voltage of 80 kV, the estimated maximum tube voltage and current were approximately 160 kV and 40 kA, respectively. When the charging voltage was increased, the characteristic X-ray intensities of tungsten K α lines increased. The K α lines were clean, and hardly any bremsstrahlung rays were detected. The X-ray pulse widths were approximately 110 ns, and the time-integrated X-ray intensity had a value of approximately 0.35 mGy at 1.0 m from the X-ray source with a charging voltage of 80 kV. Angiography was performed using a film-less computed radiography (CR) system and gadolinium-based contrast media. In angiography of non-living animals, we observed fine blood vessels of approximately 100 μm with high contrasts.

In the plasma flash X-ray generator, a 200 nF condenser is charged up to 50 kV by a power supply, and flash X-rays are produced by the discharging. The X-ray tube is a demountable triode with a trigger electrode, and the turbomolecular pump evacuates air from the tube with a pressure of approximately 1 mPa. Target evaporation leads to the formation of weakly ionized linear plasma, consisting of nickel ions and electrons, around the fine target, and intense K α lines are left using a 15-μm-thick cobalt filter. At a charging voltage of 50 kV, the maximum tube voltage was almost equal to the charging voltage of the main condenser, and the peak current was about 18 kA. The K-series characteristic X-rays were clean and intense, and higher harmonic X-rays were observed. The X-ray pulse widths were approximately 300 ns, and the time-integrated X-ray intensity had a value of approximately 1.0 mGy at 1.0 m from the X-ray source with a charging voltage of 50 kV.

Background: Telomeres are important for chromosome structure and function, protecting them against degradation. However, few studies have examined telomeres in pulmonary neuroendocrine (NE) tumors. Methods: We investigated deparaffinized sections obtained from 70 primary NE lung tumors [34 typical carcinoids (TCs), 10 atypical carcinoids (ACs), 16 large cell neuroendocrine carcinoma (LCNECs) and 10 small cell lung carcinomas (SCLCs)]. Results: Positive expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA were recognized, respectively, in 58% and 74% of TCs, and in 100% and 100% of ACs, LCNECs and SCLCs. Alteration of telomere length was greater in both LCNECs and SCLCs than in TCs. Telomerase activity was detected in LCNECs, but not in TCs. By the reverse-transcriptase polymerase chain reaction (RT-PCR), hTERC mRNA was detected in 100% of LCNECs and TCs examined, while hTERT mRNA was detected in 67% of LCNECs, but not at all in TCs. Conclusions: These results suggest that alterations in telomere length, telomerase activity, and the expression of hTERT mRNA may (i) play roles in pathogenesis in pulmonary neuroendocrine tumors, and (ii) be a useful tool for differential diagnosis between TCs and LCNECs.

In the plasma flash X-ray generator, a 200 nF condenser is charged up to 50 kV by a power supply, and flash X-rays are produced by the discharging. The X-ray tube is a demountable triode with a trigger electrode, and the turbomolecular pump evacuates air from the tube with a pressure of approximately 1 mPa. Target evaporation leads to the formation of weakly ionized linear plasma, consisting of copper ions and electrons, around the fine target, and intense Kα lines are left using a 10-µm-thick nickel filter. At a charging voltage of 50 kV, the maximum tube voltage was almost equal to the charging voltage of the main condenser, and the peak current was about 16 kA. The K-series characteristic X-rays were clean and intense, and higher harmonic X-rays were observed. The X-ray pulse widths were approximately 300 ns, and the time-integrated X-ray intensity had a value of approximately 1.5 mGy per pulse at 1.0 m from the X-ray source with a charging voltage of 50 kV.

The effect of temperature on the initiation of light-induced defects in a-Se targets of high-gain avalanche rushing photoconductor (HARP) camera tubes was studied. At room temperature, avalanche a-Se was found to be subject to both reversible and irreversible photodarkening. At 35 °C, the irreversible photodarkening component was completely absent. This result is attributed to the instantaneous annealing of light-induced metastable coordination defects at elevated temperatures. A model for the formation of permanent crystalline areas at low temperatures via transition states associated with light-induced metastable defects is proposed.

This generator consists of the following components: a constant high-voltage power supply, a filament power supply, a turbomolecular pump, and an X-ray tube. The X-ray tube is a demountable diode which is connected to the turbomolecular pump and consists of the following major devices: a molybdenum rod target, a tungsten hairpin cathode (filament), a focusing (Wehnelt) electrode, a polyethylene terephthalate X-ray window 0.25 mm in thickness, and a stainless-steel tube body. In the X-ray tube, the positive high voltage is applied to the anode (target) electrode, and the cathode is connected to the tube body (ground potential). In this experiment, the tube voltage applied was from 22 to 36 kV, and the tube current was regulated to within 100 µA by the filament temperature. The exposure time is controlled in order to obtain optimum X-ray intensity. The electron beams from the cathode are converged to the target by the focusing electrode, and clean K-series characteristic X-rays are produced through the focusing electrode without using a filter. The X-ray intensity was 26.6 µGy/s at 1.0 m from the X-ray source with a tube voltage of 30 kV and a tube current of 100 µA, and quasi-monochromatic radiography was performed using a computed radiography system.

上部気道消化管の腫瘍はほとんどが扁平上皮癌であり，非角化病変では子宮頸部と同様に異形成，上皮内癌の定義が使用されるが，角化病変では独自のcriteriaを導入して，診断することが必要である。一方肺のpreinvasive lesions前浸潤性病変として2004年のWHO分類は，(1)扁平上皮異形成，上皮内癌，(2)異型腺腫様過形成 (AAH)，(3)びまん性特発性肺神経内分泌細胞過形成の3病変が記載されている。(1)異形成は軽度，中等度，高度と進み，上皮内癌になる。さらに基底膜を破壊し，微小浸潤癌から浸潤性扁平上皮癌へ，(2)AAHは細気管支肺胞上皮癌に，さらには浸潤性腺癌に進行するといわれている。しかし (3)はtumourletやカルチノイドとの関連は言及されているが，同じ細胞起源である小細胞癌および大細胞性神経内分泌癌との関連は不明である。これらのpreinvasive lesionsからinvasive lesionsに進行するにはさまざまな遺伝子異常の蓄積が必要である。これらの病変を形態学的に正しく認識して，さらに分子生物学的手段により確証することで，早期発見に寄与し，的確な治療につなげることが重要である。

The cerium-target x-ray tube is useful in order to perform cone-beam K-edge angiography because K-series characteristic x-rays from the cerium target are absorbed effectively by iodine-based contrast media. The x-ray generator consists of a main controller and a unit with a high-voltage circuit and a fixed anode x-ray tube. The tube is a glass-enclosed diode with a cerium target and a 0.5-mm-thick beryllium window. The maximum tube voltage and current were 70kV and 0.40mA, respectively, and the focal-spot sizes were approximately 1×1mm. Cerium K-series characteristic x-rays were left using a cerium oxide powder filter, and the x-ray intensity was 14.3μGy/s at 1.0m from the source with a tube voltage of 60kV, a current of 0.40mA, and an exposure time of 1.0s. Angiography was performed with a computed radiography system using iodine-based microspheres 15μm in diameter. In angiography of non-living animals, we observed fine blood vessels of approximately 100μm with high contrasts.

This generator consists of the following components: a constant high-voltage power supply, a filament power supply, a turbomolecular pump, and an x-ray tube. The x-ray tube is a demountable diode which is connected to the turbomolecular pump and consists of the following major devices: a molybdenum rod target, a tungsten hairpin cathode (filament), a focusing electrode, a polyethylene terephthalate x-ray window 0.25mm in thickness, and a stainless-steel tube body. In the x-ray tube, the positive high voltage is applied to the anode (target) electrode, and the cathode is connected to the tube body (ground potential). In this experiment, the tube voltage applied was from 22 to 36kV, and the tube current was regulated to within 100μA by the filament temperature. The exposure time is controlled in order to obtain optimum x-ray intensity. The electron beams from the cathode are converged to the target by the focusing electrode, and x-rays are produced through the focusing electrode. Using a lithium fluoride curved crystal, clean K-series characteristic x-rays were observed without using a filter. However, bremsstrahlung x-rays were observed using a cadmium telluride detector.

No previous study has investigated neutral large amino acid transporter type 1 (LAT1) in normal lung cells, or in atypical adenomatous hyperplasia(s) (AAH) and nonmucinous bronchioloalveolar carcinoma(s) (NMBAC) of the lung. The authors examined: (1) the levels of LAT1 mRNA/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in 41 normal lung tissues and 34 NMBAC using semiquantitative reverse transcription-polymerase chain reaction; (2) LAT1 mRNA and protein expressions in 35 normal lung tissues, 34 AAH (11 lesions were interpreted as low-grade AAH and 23 as high-grade AAH), and 43 NMBAC using in situ hybridization and immunohistochemistry; and (2) the association of the incidences of LAT1 mRNA and protein expressions with cell proliferation in these lesions. The level of LAT1 mRNA/GAPDH mRNA (1) tended to be higher in NMBAC (12.0+/-8.1) than in normal lung tissues (1.0+/-0.2), and (2) covered a much wider range (from 0 to 276) in NMBAC than in normal lung tissues (from 0 to 5.8), with six NMBAC having values higher than 7.0, while 5.8 was the highest value detected in normal lung tissues. In peripheral normal lung tissues, LAT1 mRNA and protein were detected in bronchial surface epithelial cells and alveolar macrophages (but not in nonciliated bronchiolar epithelial cells, or in alveolar type I or type II cells). In bronchial surface epithelial cells, LAT1 protein appeared to be of a nodular type, which was considered to be a nonfunctional protein pattern. The incidences of positive expressions for LAT1 mRNA and protein were 54.5 and 27.3% in low-grade AAH, 65.2 and 52.2% in high-grade AAH, and 65.1 and 79.1% in NMBAC, respectively. In the case of LAT1 protein expression, significant differences could be shown between total (low-grade plus high-grade) AAH and NMBAC, and between low-grade AAH and NMBAC. Thus, in terms of the incidence of LAT1 protein expression, high-grade AAH appeared intermediate between low-grade AAH and NMBAC. The Ki-67 labeling index (a cell proliferation score) was significantly higher in those AAH and NMBAC that were LTA1-protein-positive than in their LAT1-protein-negative counterparts. In conclusion, LAT1 expression may increase with the upregulation of metabolic activity and cell proliferation in high-grade AAH and NMBAC.

Application of ultraviolet light irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution including fibroblast growth factor-2 (FGF-2) results within 30 seconds in an insoluble, flexible hydrogel. The FGF-2 molecules retained in the chitosan hydrogel remain biologically active and are released from the chitosan hydrogel upon in vivo biodegradation of the hydrogel. To evaluate the accelerating effect on wound healing of this hydrogel, full-thickness skin incisions were made in the backs of healing-impaired diabetic (db/db) mice and their normal (db/+) littermates. The mice were later killed, and histological sections of the wound were prepared. The degree of wound healing was evaluated using several histological parameters such as the rate of contraction, epithelialization, and tissue filling. Application of the chitosan hydrogel significantly advanced the rate of contraction on Days 0 to 2 in db/db and db/+ mice. Although the addition of FGF-2 into the chitosan hydrogel in db/+ mice had little effect, application of the chitosan hydrogel-containing FGF-2 further accelerated the adjusted tissue filling rate (Days 2 to 4 and Days 4 to 8) in db/db mice. Furthermore, the chitosan hydrogel-containing FGF-2 markedly increased the number of CD-34-positive vessels in the wound areas of db/db mice on Day 4. Thus, the application of chitosan hydrogel-containing FGF-2 onto a healing-impaired wound induces significant wound contraction and accelerates wound closure and healing.

High-altitude hypoxia causes pulmonary hypertension in humans and animals. Endothelin-1 (ET-1) is a novel and long-lasting vasoconstrictor. However, no study has dealt with the effects of a hypobaric hypoxic environment (HHE) on ET-1 activity in the brain. We examined 134 male rats permanently exposed to the equivalent of 5500 m altitude for 1 to 8 weeks. In these HHE rats, the mean pulmonary arterial pressure was significantly raised. The level of ET-1 protein, measured by enzyme immunoassay, increased rapidly in the lungs on exposure to HHE, but decreased in the brain. The level of ET-1 mRNA, measured by semiquantitative RT-PCR, was raised at 1, 4, and 6 weeks' exposure in the lungs and at 4 or more weeks' exposure in 3 of 8 brain regions. By in situ hybridization and immunohistochemistry of brain sections, ET-1 mRNA and protein were detected in the endothelial cells, neurons, and astrocyte-like cells in control rats. In HHE rats, the immunoreactive intensity for ET-1 protein decreased rapidly with time in these cells within the brain, although a few weakly ET-1 protein-positive cells were detected until 8 weeks' exposure to HHE. Only a few weakly ET-1 mRNA-positive endothelial cells were detected in any HHE rats. Although the reactivity for ET-1 mRNA had decreased significantly in neurons and astrocyte-like cells at 1 and 2 weeks' exposure to HHE, it was again strong in both types of cells at 4 weeks' exposure to HHE. These results raise the possibility that during exposure to HHE, ET-1 production in the lung may play a role in the development of pulmonary hypertension, while a decrease in ET-1 production within the brain may help to protect neurons by preventing or limiting the constriction of cerebral microvessels during the hypoxia induced by HHE.

The cerium-target x-ray tube is useful in order to perform cone-beam K-edge angiography because K-series characteristic x rays from the cerium target are absorbed effectively by iodine-based contrast media. The x-ray generator consists of a main controller, an x-ray tube unit with a high-voltage circuit and an insulation transformer, and a personal computer. The tube is a glass-enclosed diode with a cerium target and a 0.5-mm-thick beryllium window. The maximum tube voltage and current were 65 kV and 0.4 mA, respectively, and the focal-spot sizes were 1.2×0.8 mm. Sharp cerium K-series characteristic x rays were observed without using a filter, and the x-ray intensity was 209μGy/s at 1.0 m from the source with a tube voltage of 60 kV and a current of 0.40 mA. Angiography was performed with a computed radiography system using iodine-based microspheres 15 μm in diameter. In angiography of non-living animals, we observed fine blood vessels of approximately 100 μm with high contrasts.

Energy-selective enhanced K-edge angiography utilizing a conventional x-ray generator is described. The x-ray generator is SOFRON NST-1005, and the maximum tube voltage and current are 100 kV and 5 mA, respectively. In the present research, the tube voltage ranged from 45 to 65kV, and the tube current was regulated to optimum values. The exposure time is controlled in order to obtain optimum x-ray intensity. At a charging voltage of 60 kV, the x-ray intensity rate obtained using an aluminum and a barium sulfate filters were 58.4 and 51.6 μGy/s at 0.7m per pulse, respectively, and the dimensions of the focal spot were approximately 1×1 mm. Angiography was performed using both the aluminum and the barium sulfate filters with a charging voltage of 60 kV.

The high-voltage condensers in a polarity-inversion two-stage Marx surge generator are charged from -50 to -70 kV by a power supply, and the electric charges in the condensers are discharged to an x-ray tube after closing gap switches in the surge generator with a trigger device. The x-ray tube is a demountable diode, and the turbo molecular pump evacuates air from the tube with a pressure of approximately 1 mPa. Clean molybdenum K{alpha} lines are produced using a 20 {mu}m-thick zirconium filter, since the tube utilizes a disk cathode and a rod target, and bremsstrahlung rays are not emitted in the opposite direction to that of electron acceleration. At a charging voltage of -70 kV, the instantaneous tube voltage and current were 120 kV and 1.0 kA, respectively. The x-ray pulse widths were approximately 70 ns, and the generator produced instantaneous number of K{alpha} photons was approximately 3x10{sup 7} photons/cm{sup 2} per pulse at 0.5 m from the source of 3.0 mm in diameter.

The cerium target x-ray generator is useful in order to perform enhanced K-edge angiography using a cone beam because K-series characteristic x rays from the cerium target are absorbed effectively by iodine-based contrast mediums. The x-ray generator consists of a main controller, a unit with a Cockcroft-Walton circuit and a fixed anode x-ray tube, and a personal computer. The tube is a glass-enclosed diode with a cerium target and a 0.5−mm-thick beryllium window. The maximum tube voltage and current were 65kV and 0.4mA, respectively, and the focal-spot sizes were 1.0×1.3mm. Cerium Kα lines were left using a barium sulfate filter, and the x-ray intensity was 0.48μC/kg at 1.0m from the source with a tube voltage of 60kV, a current of 0.40mA, and an exposure time of 1.0s. Angiography was performed with a computed radiography system using iodine-based microspheres. In coronary angiography of nonliving animals, we observed fine blood vessels of approximately 100μm with high contrasts.

High-voltage condensers in a polarity-inversion two-stage Marx surge generator are charged from -40 to -60 kV using a power supply, and the electric charges in the condensers are discharged to an X-ray tube after closing the gap switches in the surge generator using a trigger device. The X-ray tube is a demountable diode, and the turbomolecular pump evacuates air from the tube with a pressure of approximately 1 mPa. Sharp K-series characteristic X-rays of molybdenum are produced without using a monochromatic filter, since the tube utilizes a disk cathode and a rod target, and bremsstrahlung rays are not emitted in the opposite direction to that of electron acceleration. The peak tube voltage increased with increasing charging voltage and increasing space between the target and cathode electrodes. At a charging voltage of -60 kV and a target-cathode space of 1.0 mm, the peak tube voltage and current were 110 kV and 0.75 kA, respectively. The pulse width ranged from 40 to 100 ns, and the maximum dimension of the X-ray source was 3.0 mm in diameter. The number of generator-produced K photons was approximately 7×1014 photons/cm2s at 0.5 m from the source.