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In the plasma flash X-ray generator, a high-voltage main condenser of approximately 200 nF is charged up to 50 kV by a power supply, and electric charges in the condenser are discharged to an X-ray tube after triggering the cathode electrode. Flash X-rays are then produced. The X-ray tube is a demountable triode connected to a turbo molecular pump with a pressure of approximately 1 mPa. As electrons from the cathode electrode are roughly focused onto a rod nickel target of 3.0 mm in diameter by the electric field in the X-ray tube, a weakly ionized linear plasma consisting of nickel ions and electrons forms by target evaporation. 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 17 kA. When the charging voltage was increased, the linear plasma formed, and the intensities of K-series characteristic X-rays increased. The K-series lines were quite sharp and intense, and hardly any bremsstrahlung rays were detected. The X-ray pulse widths were approximately 700 ns, and the time-integrated X-ray intensity had a value of approximately 30 μC/kg at 1.0 m from the X-ray source at a charging voltage of 50 kV.

The development of a portable X-ray generator with a cerium-target tube and its application to angiography are described. The portable X-ray generator consists of a main controller, a unit with a Cock–Croft circuit and an X-ray tube, and a personal computer. Negative high voltages are applied to the cathode electrode in the X-ray tube, and the tube voltage and current are regulated by the controller or the computer. The X-ray tube is a glass-enclosed double-focus diode with a cerium target and a 0.5 mm-thick beryllium window. The maximum tube voltage and current were 60 kV and 0.8 mA, respectively. The focal-spot sizes were 4 mm ×4 mm (large) and 1 mm ×1 mm (small), respectively. Angiography was performed with a computed radiography system using iodine-based microspheres. The tube voltage, the current, the distance between the imaging plate and the X-ray source, and the spot size were 60 kV, 0.4 mA, 1.5 m, and small, respectively. In this angiography, we observed coronary arteries and fine blood vessels of about 50 μm or less with high contrasts.

A fundamental study on quasi-monochromatic parallel radiography using a polycapillary plate and a copper-target X-ray tube is described. The X-ray generator consists of a negative high-voltage power supply, a filament (hot cathode) power supply, and an X-ray tube. The negative high-voltage is applied to the cathode electrode, and the anode electrode is connected to the ground. In this experiment, the tube voltage was regulated from12–25 kV, and the tube current was regulated within 3.0 mA by the filament temperature. The exposure time was controlled in order to obtain optimum X-ray intensity, and the maximum focal spot dimensions were approximately 2 mm ×1.5 mm. The polycapillary plate was J5022-21 (Hamamatsu Photonics Inc.), and the plate thickness was 1.0 mm. The outer, effective, and hole diameters were 87 mm, 77 mm, and 25 μm, respectively. Quasi-monochromatic X-rays were produced using a 10 μm-thick copper filter, and these rays were formed into parallel beams by the polycapillary, and the radiogram was taken using a computed radiography system utilizing imaging plates. In the measurement of image resolution, the resolution fell according to increases in the distance between the chart and imaging plate using a polycapillary. We could observe a 50 μm tungsten wire clearly, and fine blood vessels of approximately 100 μm were visible in angiography.

Telomeres are important in chromosome structure and function, protecting against their degradation. However, few studies have examined telomeres in growth plates within articular cartilage during normal development. We investigated frozen sections that were obtained from 57 reference autopsy cases (aged from 16 weeks of gestation to 91 years) and from 2 patients with thanatophoric dysplasia. In the reference cases, telomere length was significantly longer in growth plates obtained from the 10 cases that were aged from 16 weeks of gestation to 10 years than in those from 47 of the adult cases (aged 20 to 91 years). In fetal, neonatal, and child cases, telomerase activity was significantly higher in the hypertrophied zone (HZ) in growth plates than in the other 3 zones. The hTERT mRNA staining intensity (staining area) was stronger (larger) in HZ and the proliferating zone than in the calcified zone and resting zone. In thanatophoric dysplasia, telomere length and telomerase activity were short and low, respectively, compared with those of normal growth plates at an equivalent age, and expression of hTERT mRNA was negative or weakly positive in all 4 zones within growth plates. These results suggest that telomere length and telomerase activity have significant effects in the growth plates of articular cartilage, particularly at developmental ages from fetus to child. We speculate that short telomere length and low telomerase activity may be important for chondrocyte differentiation in rhizomeric shortening of the limbs in thanatophoric dysplasia.

The development of an extremely soft x-ray generator with a tungsten-target tube and its applications including radiography are described. This generator consists of a high-voltage transformer, a filament power supply, and an x-ray tube. Negative high voltages are applied to the cathode electrode in the x-ray tube, and the tube voltage and current are regulated by the input voltage of the transformer and the filament voltage, respectively. The x-ray tube is a glass-enclosed double-focus diode with a tungsten target and a 0.2 mm-thick beryllium window. The maximum tube voltage and the electric power were 60 kV and 400 W, respectively. The focal-spot sizes were 4×4 (large) and 1×1 mm (small), respectively. Radiography was performed with a computed radiography system. In angiography using iodine-based microspheres, we observed fine blood vessels of about 50 μm or less with high contrasts. Using this generator, we designed an experimental setup for disinfection achieved with extremely soft x rays.

In the plasma flash x-ray generator, a high-voltage main condenser of approximately 200 nF is charged up to 50 kV by a power supply, and electric charges in the condenser are discharged to an x-ray tube after triggering the cathode electrode. Flash x rays are then produced. The x-ray tube is a demountable triode connected to a turbo molecular pump with a pressure of approximately 1 mPa. As electrons from the cathode electrode are roughly focused onto a rod nickel target of 3.0 mm in diameter by the electric field in the x-ray tube, a weakly ionized linear plasma consisting of nickel ions and electrons forms by target evaporation. 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 17 kA. When the charging voltage was increased, the linear plasma formed, and the intensities of K-series characteristic x rays increased. The K-series lines were quite sharp and intense, and hardly any bremsstrahlung rays were detected. The x-ray pulse widths were approximately 700 ns, and the time-integrated x-ray intensity had a value of approximately 30 μC/kg at 1.0 m from the x-ray source at a charging voltage of 50 kV.

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 characteristic x rays are produced. 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 20 kA. When the charging voltage was increased, the linear plasma formed, and the K-series characteristic x-ray intensities increased. The K lines were quite sharp and intense, and hardly any bremsstrahlung rays were detected at all. The x-ray pulse widths were approximately 700 ns, and the time-integrated x-ray intensity had a value of approximately 30 μC/kg at 1.0 m from the x-ray source with a charging voltage of 50 kV.

Hepatocyte growth factor (HGF) regulates cell growth, cell motility, and morphogenesis in various types of cells, including epithelial and endothelial cells, indicating that it probably promotes epithelial repair and neovascularization during wound healing. To better understand the effects of HGF on wound healing, we performed human HGF-gene transfer into skin wounds in rats. The rat HGF mRNA levels, and human and rat HGF protein concentrations in the wounds in HGF gene-transfer rats were significantly elevated at 3 days, 3 to 14 days, and 3 and 14 days after gene transfer, respectively. An expression of human HGF mRNA and protein was revealed in squamous cells in the epidermis, in endothelial cells and smooth muscle cells in blood vessels, and in fibroblasts in granulation tissues at 3, 7, and 14 days after gene transfer in HGF gene-transfer rats. The wound lesion area in HGF gene-transfer rats was significantly less than that in control rats from 3 to 7 days after gene transfer. The re-epithelialization rate, microvessel counts in granulation tissues, proliferating cell nuclear antigen index of fibroblasts in granulation tissues, and the proliferating cell nuclear antigen index in the epidermis of HGF gene-transfer rats were significantly increased at 3 and 7 days after gene transfer. Semiquantitative reverse transcriptase-polymerase chain reaction revealed that the expression levels of transforming growth factor-beta1 and Colalpha2(I) mRNAs in the wounds of HGF gene-transfer rats were significantly decreased at 7 and 14 days, respectively. The hydroxyproline concentration in the wound was significantly less in HGF gene-transfer rats than in control rats at 3 days after gene transfer. These results suggest that HGF gene transfer into a skin wound may aid re-epithelialization and neovascularization in the early phase of wound healing, and that HGF may play a role in modulating cutaneous wound healing.

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodelling of the heart. In rat cardiac ventricles, pressure and volume overload are well known to be associated with changes in cardiac myosin heavy chain (MHC) isoforms. To study the effects of HHE on the MHC profile in the ventricles, 83 male Wistar rats were housed in a chamber at the equivalent of 5500 m altitude for 1-8 weeks. Pulmonary arterial pressure, right ventricular free wall (RVFW) weight, the ratio of RVFW weight over body weight (BW), the ratio of left ventricular free wall (LVFW) weight over BW, and myocyte diameter in both ventricles showed significant increases after 1 week, 2 weeks, 1 week, 6 weeks, and 4 weeks of HHE, respectively. Semi-quantitative reverse transcriptase-polymerase chain reaction revealed that beta-MHC mRNA expression was increased significantly in both ventricles at 6 and 8 weeks of HHE, whereas alpha-MHC mRNA expression was decreased significantly at 6 and 8 weeks of HHE in the right ventricle (RV) and at 6 weeks of HHE in the left ventricle (LV). The percentage of myosin containing the beta-MHC isoform was increased significantly at 4-8 weeks of HHE in RV and at 6 weeks of HHE in LV. In situ hybridization showed that the area of strong staining for beta-MHC mRNA was increased in both ventricles at 8 weeks of HHE, and showed a decrease from RVFW to cardiac septum, and from cardiac septum to LVFW. These results suggest that HHE has a significant effect on the expression of both MHC mRNA and protein in the heart, particularly in RV. These changes may reflect a role for cardiac MHC in the response to pulmonary hypertension in HHE.

For the metastasis and invasion of cancer cells, destruction of extracellular matrix is essential. In this process, collagen is broken down by some matrix metalloproteinases. Matrix metalloproteinase 2 (MMP2) is able to cleave type IV collagen, and membrane-type-1-matrix metalloproteinase (MT1-MMP) induces activation of proMMP2. We investigated the expressions of MT1-MMP and MMP2 and their relation to both clinicopathologic parameters and clinical outcome in non-small cell lung carcinomas (NSCLC). Eighty-nine specimens of NSCLC were examined using in situ hybridization and immunohistochemistry. Each metalloproteinase was expressed within the cytoplasm of tumor cells with or without stromal cells in NSCLC. Tumors in which tumor cells strongly stained for MT1-MMP mRNA or protein made up more than 50% of the tumor area were found in 44 and 26% of cases, respectively. The corresponding values for MMP-2 mRNA and protein, were 51 and 26%. Our analysis of clinicopathological findings revealed a significant positive relationship between MT1-MMP mRNA and p-M. The correlation between MMP2 protein-staining status and overall survival rate reached significance in the univariate analysis. However, an association was not demonstrated in the multivariate analysis. The detection of MT1-MMP and MMP2 is likely to be of limited value in informing the prognosis in NSCLC.

We have fabricated c-axis oriented thin films of the oxide thermoelectric material Ca3Co4O9(CCO) on MgO(100), SrTiO3(100) (STO), YSZ polycrystal and YSZ(100) substrates by pulsed laser deposition. The resistivity of CCO thin films on SrTiO3 and YSZ substrates hardly varied with increasing temperature from 300 to 700 K. On the other hand, the resistivity of the films on MgO was relatively high, because of an impurity phase grown on the surface and the change of lattice constant at high temperature. From the microstructure of the CCO films on STO observed by transmission electron microscopy (TEM) techniques, a main structure of cobaltite [Ca2CoO3]xCoO2 has been found with identical a, b1 and c parameters: a=0.48nm, b=0.45nm and c=1.07nm. The composition ratios of the main phase and secondary phase in the CCO films were Ca:Co=0.98:1.0 and Ca:Co=0.39:1.0, respectively.

The expression of p27(Kip1), a negative regulator of the cell cycle, has been reported to correlate with the biological behavior and prognosis of several tumors. However, its prognostic importance in transitional cell carcinoma of the upper urinary tract (TCC-UUT) has not previously been investigated. We investigated p27(Kip1) protein expression using immunohistochemistry in 132 cases of TCC-UUT and also its relation to proliferating cell nuclear antigen (PCNA) immunoreactivity, p53 oncoprotein immunoreactivity, clinicopathologic parameters, and clinical outcome. A positive expression of p27(Kip1) protein was recognized in 94.7% of the samples and was apparent within tumor nuclei. In the normal urothelium, its expression was identified in all cell layers. A positive expression of p53 oncoprotein was recognized in 27.2% of the patients. The PCNA index was 7.4 to 93.1% (mean, 66.4%). Examination of the relationships between the expression of p27(Kip1) protein and clinicopathologic findings, PCNA index, and the expression of p53 oncoprotein revealed that the expression of p27(Kip1) protein decreased significantly with stage and grade. In a univariate analysis of disease-free and overall survival rates, no correlation was found between the expression of p27(Kip1) protein and prognosis. The expression of p27(Kip1) protein appears to be of little or no value in informing the prognosis in TCC-UUT.

Poorly differentiated adenocarcinoma without papilla or tubule formation of the extrahepatic bile duct is rare. Here we present a case (a 42-year-old Japanese woman) without either pancreatobiliary maljunction or liver disease. The patient had obstructive jaundice. Imaging studies revealed a bile duct tumor obstructing the common bile duct and invading the surrounding tissues. Pathologic examination revealed a dense periductal growth of poorly differentiated adenocarcinoma containing signet-ring cells, but without papilla or tubule formation in the extrahepatic bile duct. The tumor cells directly invaded the pancreatic parenchyma and the portal vein. In the extrahepatic bile duct, poorly differentiated adenocarcinoma may be established as a distinct clinicopathologic entity if the tumors are characterized by:1) the absence of papilla or tubule formation, 2) Asian preponderance, 3) occurrence at a younger age than is usual for patients with biliary cancers, and 4) an aggressive mural invasiveness.

The quantum efficiency of photo-charge generation and avalanche multiplication in amorphous selenium (a-Se) photodetectors were measured over considerable ranges of photoexcitation wavelengths (420–600 nm) and electric fields (10–112.5 V/μm) for several different a-Se target thicknesses (8–35 μm). An avalanche multiplication factor of 1000 is shown for a 35 μm thick a-Se layer at an electric field of 98 V/μm. The experimental results on quantum efficiency can be explained by the Onsager theory of electron–hole pair dissociation in conjunction with an electric field-induced delocalization of states.

Carcinoma of the upper urinary tract is a relatively rare neoplasm, and few studies have dealt with clinicopathological findings and prognosis in a large number of cases. The purpose of our investigation was to look for a possible relation between E-cadherin (E-CD) immunoreactivity and clinicopathologic findings or clinical outcome in transitional-cell carcinoma of the upper urinary tract (TCC-UUT). To this end, we investigated E-CD immunoreactivity in 154 cases of TCC-UUT. E-CD immunoreactivity was recognized as being of "normal" pattern in 29.2% of samples. The relationship between E-CD immunoreactivity and clinicopathologic findings was significant for stage, grade and pattern of growth. The 5-year disease-free rate for 147 cases and 5-year overall survival rate for 154 cases were 55.7% and 71.5%, respectively. A univariate analysis of survival revealed that stage, grade, pattern of growth and E-CD immunoreactivity all had a significant effect on disease-free and overall survival rates. In the final models of multivariate analysis, however, we found that, for disease-free survival and for overall survival, only stage was a factor for progression or prognosis. Detection of E-CD immunoreactivity appears to be of limited value in deciding the prognosis of TCC-UUT.

High-altitude hypoxia causes polycythaemia and a hypercoagulable state in humans and animals. This study examines the effects of a hypobaric, hypoxic environment (HHE) on the blood coagulation system in rats. A total of 170 male Wistar rats were housed in a chamber at the equivalent of 5500 m in altitude for 1–12 weeks. After 2 weeks of exposure to HHE, platelet counts decreased significantly; after 4 weeks, the prothrombin and activated partial thromboplastin times were significantly prolonged, compared with those of control rats. In addition, individual coagulation factors (VII, IX, X, XI, and XII) were significantly decreased at 8 weeks (P

Experimental pulmonary hypertension that develops in hypobaric hypoxia is characterized by structural remodeling of the lung. Proteomics - which may be the most powerful way to uncover unknown remodeling proteins involved in enhancing cardiovascular performance - was used to study 150 male Wistar rats housed for up to 21 days in a chamber at the equivalent of 5500 m altitude level. After 14 days' exposure to hypobaric hypoxia, pulmonary arterial pressure (PAP) was significantly increased. In lung tissue, about 140 matching protein spots were found among 8 groups (divided according to their hypobaric period) by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) (pH4.5-pH6.5, 30 kDa-100 kDa). In hypobaric rats, three spots were increased two-fold or more (vs. control rats) in two-dimensional differential in-gel electrophoresis (2D-DIGE). The increased proteins were identified, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), as one isoform of heat shock protein 70 (HSP70) and two isoforms of protein disulfide isomerase associated 3. This result was confirmed by Western blotting analysis of 2D-PAGE. Conceivably, HSP70 and PDIA3 may play roles in modulating the lung structural remodeling that occurs due to pulmonary hypertension in hypobaric hypoxia.

The p53 gene, which is located on human chromosome 17, encodes for a nuclear phosphoprotein and is thought to regulate cell growth and proliferation. Although the immunoreactivity for p53 oncoprotein in transitional cell carcinoma (TCC) of the urinary bladder has been shown to correlate with clinicopathologic findings and prognoses, there have been no such reports on TCC of the upper urinary tract (TCC-UUT). The present study investigated the prognostic value of p53 oncoprotein in TCC-UUT. Formalin-fixed, paraffin-embedded tumor tissues from 149 TCC-UUT patients were analyzed using immunohistochemical staining. Immunohistochemically, p53 oncoprotein was recognized as positive in 26.8% of the samples. The immunoreactivity for p53 oncoprotein was significantly (P < .05) correlated with both stage, grade, and pattern of growth. The 5-year disease-free and overall survival rates were 58.4% and 69.7%, respectively. A univariate analysis of survival showed that stage, grade, pattern of growth, and the immunoreactivity for p53 oncoprotein have a significant effect on disease-free and overall survival rates. In the final models of multivariate analysis, only stage for disease-free survival, and stage and the immunoreactivity for p53 oncoprotein for overall survival were found to be progressive or prognostic factors. Detection of immunoreactivity for p53 oncoprotein appears to be of real value in deciding the prognosis of TCC-UUT.

Few studies have investigated the prognostic value of a variety of cell-biological parameters in cases of urachal adenocarcinoma, a rare neoplasm. The authors examined three cell-biological parameters--DNA status, proliferating cell-nuclear antigen (PCNA) immunostaining, and argyrophilic nucleolar-organizer region (AgNOR) counts--in surgically resected, formalin-fixed, paraffin-embedded urachal adenocarcinomas from 41 patients. The authors quantified DNA distribution in 200 cancer cells from a section of each tumor, stained with 4',6-diamidino-2-phenylindole, using a microspectrophotometer. The authors also measured the number of PCNA immunostaining cells in 1,000 nuclei, and AgNORs counts in 200 nuclei, from sections of each tumor. There were eight specimens with group 1 DNA distribution (defined as a DNA content of under 4c in >90% of the cells), 21 of group 2 DNA distribution (more than 4c in >10% of the cells and more than 6c in 10% of the cells). The percentage of PCNA-positive cells was 19% to 91% (median, 59.5%), and the mean AgNOR count was 2.2 to 8.8 (median, 5.3) granules per nucleus. The 5-year survival rate for all 41 patients was 50.2%. Initial univariate analyses indicated that tumor stage, histological differentiation, and DNA status had a significant effect on survival. In the final models using multivariate analysis, only tumor stage and histological differentiation were found to be prognostic factors. These investigations confirm the vital importance of tumor stage and histological differentiation as predictors of patient survival. The three cell-biological parameters the authors studied do not appear to be important parameters for predicting survival.

It is difficult to distinguish desmoplastic malignant mesothelioma (DMM) from fibrous pleuritis (FP). We investigated the utility of immunohistochemistry as a way of differentiating between DMM and FP. We examined 11 DMMs and 46 FPs with the aid of antibodies against 18 cytokeratin (CK) subtypes, calponin, caldesmon, desmin, and GLUT-1. The best sensitivity and specificity cut-off values in the receiver operating characteristic curves (ROC) for CKs 7, 8, 17, 18, and 19, and GLUT-1 were each above 60%. When cases with either DMM or FP were partitioned by the staining score associated with the best sensitivity and specificity cut-off values in ROC, the incidence of a positive expression for CKs 7, 8, 17, 18, and 19, and GLUT-1 was significantly higher in DMM than in FP. In conclusion, immunohistochemistry for CKs 7, 8, 17, 18, and 19, and GLUT-1 may be useful, alongside histological characteristics, for separating DMM from FP.

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.

多発粘膜内癌を伴う腹部食道原発の有茎性偽肉腫を経験したので報告する.症例は60歳の男性.主訴は嚥下障害.近医にて上部消化管造影X線検査で胃の巨大腫瘤を指摘され, 当科紹介受診となる.内視鏡検査にて腹部食道を基部とする手拳大の有茎性腫瘤 (13×7×6cm) の胃内への脱出を認め, ルゴール染色所見では切歯列28cmから腫瘤茎部まで斑状の不染帯が多発していた.生検では同不染帯に扁平上皮癌, 腫瘤には異型性を伴う紡錐形細胞を認めた.手術は右開胸開腹胸部食道全摘 (R2), 胸骨後胃管再建術を施行した.扁平上皮癌の深達度は大部分が上皮内 (ep), 一部粘膜筋板 (mm) で第2群リンパ節に転移を認めた.腫瘤には扁平上皮癌からの移行像は認められず, 免疫染色, 電顕所見から偽肉腫と診断された.多中心性の扁平上皮癌と偽肉腫の併存はまれであり, 多発する上皮内癌の一部からの刺激で間質細胞が異常増殖したものと考えられた.

A one-inch X-ray vidicon (imaging camera tube) with a polycrystalline cadmium telluride (CdTe) photoconductive target has been developed. This vidicon has a 10.5μm thick CdTe layer deposited by RF sputtering and can attain an X-ray signal current of about 200 nA/cm2 for 2.58 mC/kg/min (10R/ min). This value is higher than the 45 nA/cm2 of conventional PbO X-ray vidicons. The dark current is about 5 nA/cm2 at a target voltage of 35 V at room temperature. The resolution of the device exceeds 251p/mm (20μm). In addition, by using a sputtering technique which can obtain large and uniform film, simultaneous deposition of many conventional and large vidion targets can easily be performed.

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 14) 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.

To assess whether early lung cancer prediction might be informed by an mRNA assay for 5-fluorouracil pathway genes in peripheral blood mononuclear cells (PBMNCs), we examined specimens taken from 51 adenocarcinoma patients and 38 controls (including six patients with benign tumors). PBMNCs and tumor-tissue specimens were taken for measurement of the mRNAs of various 5-fluorouracil pathway genes [thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyl transferase (OPRT)]. By quantitative RT-PCR, all four mRNAs were detected in both PBMNCs and tumor tissues. In PBMNCs, TS mRNA/GAPDH mRNA levels were significantly higher in adenocarcinoma patients than in the controls, and significantly higher for pathological stages 2–4 and lymph-node involvement pN1–pN3 than for pathological stage 1 and pN0, respectively. No correlation between PBMNCs and tumor-tissue specimens was found for the level of any mRNA. Thus, the measurement of TS mRNA in PBMNCs might aid the diagnosis of lung adenocarcinoma.

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.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.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.The detection of GRP78 overexpression would appear to provide valuable information for the prognosis of UC-UUT.

Aim Protein kinase C (PKC), cloned as a serine/threonine kinase, plays key roles in diverse intracellular signalling processes and in cardiovascular remodelling during pressure overload or volume overload. We looked for correlations between changes in PKC isoforms (levels and/or subcellular distributions) and cardiac remodelling during experimental hypobaric hypoxic environment (HHE)-induced pulmonary hypertension. Methods To study the PKC system in the heart during HHE, 148 male Wistar rats were housed for up to 21 days in a chamber at the equivalent of 5500 m altitude level (10% O(2)). Results At 14 or more days of exposure to HHE, pulmonary arterial pressure (PAP) was significantly increased. In the right ventricle (RV): (1) the expression of PKC-alpha protein in the cytosolic and membrane fractions was increased at 3-14 days and at 5-7 days of exposure respectively; (ii) the cytosolic expression of PKC-delta protein was increased at 1-5, 14 and 21 days of exposure; (3) the membrane expressions of the proteins were decreased at 14-21 (PKC-betaII), 14-21 (PKC-gamma), and 0.5-5 and 21 (PKC-epsilon) days of exposure; (4) the expression of the active form of PKC-alpha protein on the plasma membrane was increased at 3 days of exposure (based on semiquantitative analysis of the immunohistochemistry). In the left ventricle, the expressions of the PKC mRNAs, and of their cytosolic and membrane proteins, were almost unchanged. The above changes in PKC-alpha, which were strongly evident in the RV, occurred alongside the increase in PAP. Conclusion PKC-alpha may help to modulate the right ventricular hypertrophy caused by pulmonary hypertension in HHE.

Formerly believed to be mesotheliomas, localized or solitary fibrous tumors (LFTs) are rare tumors, most common in the pleura but also reported to involve the lung and other parts of the body. Patients with LFTs are usually middle aged but the overall age distribution is wide. Digital clubbing and pleural effusions may be seen. Their size is quite variable ranging from 1 to 2 cm to masses filling an entire hemithorax. This variation in size can be reflected in their radiographic appearance. Tumors larger than 10 cm may behave in a malignant fashion. Calcification occurs in a minority of the cases. Rarely, an LFT will grow into an airway and in those instances it will mimic a tumor of endobronchial or endotracheal origin. Microscopically, a hemangiopericytoma-like pattern and a cellular pattern may co-exist along with the more common “pattern-less” pattern. Fine needle aspirates show scant to variable cellularity, fragments of ropy collagen, and oval to spindly cells with bland-looking oval to round nuclei.

Under the name “Uncommon Endobronchial Surface Tumors,” we consider generally benign epithelial proliferations of the trachea and bronchi whose common denominator is a papillary growth pattern. Currently, the World Health Organization recognizes three major histopathologic types: squamous, glandular, and mixed-type papillomas.

Reported herein is a case of malignant pleural mesothelioma, initially diagnosed on cervical lymph node biopsy. A 58-year-old man, without obvious evidence of asbestos exposure, exhibited repeated pleural effusion (cause unclear), which was resolved by diuretics. A neck mass was apparent and was identified pathologically as a lymph node metastasis of malignant mesothelioma. F-18 fluorodeoxyglucose positron emission tomography/CT established the diagnosis of malignant pleural mesothelioma. Two conclusions emerge from this report: (i) cervical lymph node metastasis of pleural mesothelioma, although rare, should be included in differential diagnosis; and (ii) positron emission tomography/CT is useful for establishing a diagnosis of mesothelioma.

Human intestinal spirochetosis is a colorectal infectious disease caused by 2 Brachyspira species. Its diagnosis is established by histology, culture, and polymerase chain reaction, but the value of cytologic examination in routine practice remains unclear. In this study, imprint cytology of biopsy specimens was examined for cytologic features specific to human intestinal spirochetosis. Specimens were obtained from 65 colorectal regions (1-3 regions from each case) in 25 ultrastructurally and/or genetically confirmed human intestinal spirochetosis cases (20 with Brachyspira aalborgi, 3 with B pilosicoli, 2 with both genotypes). In cytologic specimens, spirochetes tended to be floating freely within the mucus and intestinal fluid, whereas the "fringe formation" of spirochetes typically observed in histologic specimens was indistinct in cytologic specimens. Spirochetes were identified in 58 regions (89.2%) and 23 cases (92.0%) by cytology, against in 50 regions (76.9%) and 22 cases (88.0%) by histology (no significant differences). In 6 of 8 regions exhibiting positive cytology and negative histology, B pilosicoli was present within the mucus. Hence, B pilosicoli may tend to float in the mucus. In conclusion, cytologic examination would be useful for the routine identification of human intestinal spirochetosis, especially if B pilosicoli is involved. Further, we suggest the existence of differences in biological behavior between these spirochetes.

In an attempt to differentiate malignant pleural mesothelioma from pulmonary adenocarcinoma by histochemical and immunohistochemical means, the glycoconjugate profiles of five reactive mesothelial lesions, 29 mesotheliomas (20 epithelial, three biphasic, and six fibrous types), and 38 well-differentiated pulmonary adenocarcinomas (34 papillary, two tubular, and two bronchioloalveolar types) were tested with ABH blood group-related antigens (BGR-Ag) antibody and Helix pomatia agglutinin (HPA) which agglutinates human type A erythrocytes. Formalin-fixed, paraffin-embedded sections were stained by the avidinbiotin-peroxidase complex method. Reactive mesothelial lesions and malignant mesothelioma of the pleura were not stainable with BGR-Ag antibody or HPA, irrespective of the blood group type. In pulmonary adenocarcinoma, however, the test with BGR-Ag antibody showed a high positive rate with the compatible blood group type, especially in type O cases (83%). Using HPA, reactions of adenocarcinoma with types A and AB also demonstrated high positive results (94% and 100%, respectively), but even with types B and O positive reactions occurred in 80% and 33% of cases, respectively. The findings suggest that positive reactions with either BGR-Ag antibody or HPA can be indicative of pulmonary adenocarcinoma.

Adenomatoid tumorは傍精巣器官に好発し, 中皮起原が有力とされている比較的まれな良性腫瘍である.今回われわれは精巣鞘膜に発生したAdenomatoid tumorの1例を経験したので, その捺印細胞所見を中心に若干の文献的考察を加えて報告する.捺印細胞の特徴として, 1) 核内細胞質封入体, 2) 核クロマチンの微細顆粒状均等分布, 3) 小型で1個の核小体, 4) レース状で不均一空胞をもつ細胞質, 5) 正常中皮細胞様結合, 6) PAS染色陰性, アルシアン青染色陽性の粘液産生, 7) 上皮様細胞の出現が内皮様細胞の出現より優位, などがあげられた.組織所見で立方状の上皮様細胞と扁平な内皮様細胞が不規則な腺管形成するかあるいは索状配列を示し, 間質には弾性線維の増生やリンパ球の集籏をみた.免疫組織化学的にはサイトケラチン, ビメンチンが陽性で第VIII因子関連抗原, EMAが陰性であった.電顕所見では腫瘍細胞が構成する腺管内腔面に多数の微絨毛を認め, 細胞質内にトノフィラメントを有し, 細胞相互はデスモゾームにより接着していた.これらの所見は本腫瘍が中皮由来であるという考えと矛盾しないと思われた.

Objective System l-amino acid transport mediates the uptake of aromatic neutral amino acids and nutritionally essential amino acids from extracellular fluids. Little is known about the role of l-amino acid transporter 1 (LAT1), a member of the system l-amino acid transporter family, in non-small-cell lung carcinomas (NSCLCs). Patients and methods We examined (i) LAT1 mRNA levels in 40 normal lung tissues (NLTs) and 237 NSCLCs using semiquantitative RT-PCR, (ii) LAT1 protein expression in 295 NSCLCs using immunohistochemistry, and (iii) whether LAT1 mRNA and protein expressions were related to clinicopathologic findings and outcome. Results The LAT1 mRNA level was significantly higher in all NSCLCs (6.81±1.13) than in NLT (1.00±0.18). The LAT1 mRNA level showed no association with clinicopathologic findings or outcome. LAT1 protein was detected with a diffuse or granular appearance within the cytoplasm and/or on the plasma membrane of tumor cells. When tumors were graded as positive if staining indicating a plasma membrane expression of LAT1 protein made up more than 10% of the tumor, the frequency of this membrane expression was found to be associated with tumor histology, differentiation grade, pathologic stage, T classification, pleural invasion, lymph-vessel invasion, and overall survival rate. Conclusion Detection of a plasma membrane expression of LAT1 protein would appear to be of value in informing the prognosis in NSCLC cases.

A high-speed x-ray tomography system is useful for observing high-speed phenomena. The experimental setup for tomography consists of a tungsten-target x-ray generator, a tungsten collimator, and a computed radiography system. An object was exposed by a 2-mm-thick fun beam from the x-ray generator, and scattering x-rays from the slice plane were detected using an imaging plate through a tungsten collimator with hole diameters of 0.8 mm. Because the exposed dose for tomography was almost equal to those obtained using two intense flash x-ray generators, ultra-high-speed tomography could be performed.

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 ferrum ions and electrons, around the fine target, and intense K-series characteristic x-rays are produced from the plasma axial direction. 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 15 kA. In the spectral measurement, Kβ rays were intense, and higher harmonic x-rays were observed. The pulse widths were 0.5 μs, and the maximum x-ray intensity was approximately 300 μGy.

X-ray fluorescence (XRF) analysis is useful for measuring density distributions of contrast media in vivo. An XRF camera was developed for carrying out mapping for iodine-based contrast media used in medical angiography. Objects are exposed by an X-ray beam from a cerium target. Cerium K-series X-rays are absorbed effectively by iodine media in objects, and iodine fluorescence is produced from the objects. Next, iodine Kalpha fluorescence is selected out by use of a 58-microm-thick stannum filter and is detected by a cadmium telluride (CdTe) detector. The Kalpha rays are discriminated out by a multichannel analyzer, and the number of photons is counted by a counter card. The objects are moved and scanned by an x-y stage in conjunction with a two-stage controller, and X-ray images obtained by iodine mapping are shown on a personal computer monitor. The scan pitch of the x and y axes was 2.5 mm, and the photon counting time per mapping point was 2.0 s. We carried out iodine mapping of non-living animals (phantoms), and iodine Kalpha fluorescence was produced from weakly remaining iodine elements in a rabbit skin cancer.

Thromboangiitis obliterans (TAO, Buerger's disease) is an idiopathic, recurrent, segmental, nonatherosclerotic, inflammatory, occlusive vascular disease with a poorly understood pathogenesis. Intestinal or multi-organ involvement is rare. Recent immunohistochemical analyses of ordinary TAO have indicated an inflammatory and immunologic pathogenesis. We report a case of TAO involving multiple large vessels. By immunohistochemistry, CD3(+) T cells were revealed around the recanalization sites within the abdominal aorta. CD4(+) T cells were almost equal in number to CD8(+) T cells. These findings indicate the participation of inflammatory and immunologic processes in TAO with multi-organ involvement (as in ordinary TAO).

An indirect flat-imager with programmable avalanche gain and field emitter array (FEA) readout is being investigated for low-dose x-ray imaging with high resolution. It is made by optically coupling a structured x-ray scintillator CsI (Tl) to an amorphous selenium (a-Se) avalanche photoconductor called HARP (high-gain avalanche rushing photoconductor). The charge image created by HARP is read out by electron beams generated by the FEA. The proposed detector is called SAPHIRE (Scintillator Avalanche Photoconductor with HIgh Resolution Emitter readout). The avalanche gain of HARP depends on both a-Se thickness and applied electric field ESe. At ESe of > 80 V/μm, the avalanche gain can enhance the signal at low dose (e.g. fluoroscopy) and make the detector x-ray quantum noise limited down to a single x-ray photon. At high exposure (e.g. radiography), the avalanche gain can be turned off by decreasing ESe to < 70 V/μm. In this paper the imaging characteristics of the FEA readout method, including the spatial resolution and noise, were investigated experimentally using a prototype optical HARP-FEA image sensor. The potential x-ray imaging performance of SAPHIRE, especially the aspect of programmable gain to ensure wide dynamic range and x-ray quantum noise limited performance at the lowest exposure in fluoroscopy, was investigated.

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 (111) plane silicon crystal is employed. The x-ray beams from the source are confined by an x-y diaphragm, and monochromatic cone beams are formed by the crystal and three lead plates. The x-ray generator consists of a main controller and a unit with a high-voltage circuit and a 100-µm-focus x-ray tube. In this experiment, the maximum tube voltage and current were 35 kV and 0.50 mA, respectively, and the x-ray intensity of the microfocus generator was 343 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 15.5 keV.