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INTRODUCTION To confirm the feasibility of hypofractionated proton beam therapy (PBT), we compared the acute adverse event rates and International Prostate Symptom Score (IPSS) in prostate cancer patients treated with hypofractionated versus conventionally fractionated (2.0 Gy relative biological effectiveness (RBE)/fraction) PBT. METHODS We reviewed 289 patients with prostate cancer, of whom 73, 100, and 116 patients were treated with 2.0, 2.5, and 3.0 Gy (RBE)/fraction, respectively. The endpoints were acute genitourinary and gastrointestinal toxicities and the IPSS, evaluated up to 6 months after PBT initiation. RESULTS No significant differences were found in acute toxicity rates or the IPSS among the fractionation schedules. Diabetes mellitus, age, and androgen deprivation therapy were not identified as factors associated with the IPSS. CONCLUSION There were no significant differences in adverse events or quality of life among the three fractionation schedules early after PBT.

BackgroundGlioblastoma peritumoral edema (PE) extent is associated with survival and progression pattern after tumor resection and radiotherapy (RT). To increase tumor control, proton beam was adopted to give high-dose boost (> 90 Gy). However, the correlation between PE extent and prognosis of glioblastoma after postoperative high-dose proton boost (HDPB) therapy stays unknown. We intend to utilize the PE status to classify the survival and progression patterns.MethodsPatients receiving HDPB (96.6 GyE) were retrospectively evaluated. Limited peritumoral edema (LPE) was defined as PE extent 1 cm from the tumor bed edge.ResultsAfter long-term follow-up (median 88.7, range 63.6–113.8 months) for surviving patients with (n = 13) and without (n = 32) LPE, the median overall survival (OS) and progression-free survival (PFS) were 77.2 vs. 16.7 months (p = 0.004) and 13.6 vs. 8.6 months (p = 0.02), respectively. In multivariate analyses combined with factors of performance, age, tumor maximum diameter, and tumor resection extent, LPE remained a significant factor for favorable OS and PFS. The rates of 5-year complete response, EPD, and distant metastasis with and without LPE were 38.5% vs. 3.2% (p = 0.005), 7.7% vs. 40.6% (p = 0.04), and 0% vs. 34.4% (p = 0.02), respectively.ConclusionsThe LPE status effectively identified patients with relative long-term control and specific progression patterns after postoperative HDPB for glioblastoma.

The Rho-associated coiled-coil-containing protein kinase (ROCK) pathway is known to influence metastasis in several cancers; however, the impact of the pathway on clinical outcomes in patients undergoing radiotherapy remains unknown. In the present study, the expression of RhoA, RhoC, ROCK-1, ROCK-2 and p53 was immunohistochemically evaluated using biopsy specimens obtained from 49 patients with stage II–III cervical squamous cell carcinoma treated with concurrent chemoradiotherapy (CCRT). The relationship between the expression of these proteins and patient outcomes was investigated. RhoA overexpression was associated with significantly impaired disease-free survival and distant metastasis-free survival (P = 0.045 and P = 0.041, respectively) in stage III cancer patients. No differences in survival were observed based on the expression of the other proteins among stage III cancer patients. In stage II cancer patients, no differences in survival were noted based on the expression of any of the proteins. The expression of RhoA was able to successfully differentiate cervical cancer patients with distant metastasis after CCRT. This information may help stratify patients according to the risk of metastasis, thereby leading to the potential to provide individualized treatment.

Neuroblastoma (NB) predominantly presents as high-risk disease, requiring intensive multimodal therapy. Proton beam therpy (PBT) is a promising option for many childhood cancers, but is not widely available. Patients with NB hoping to receive PBT may therefore need to be transferred between institutions during intensive multimodal therapy, risking undesirable effects. We evaluated patients with high-risk NB who received PBT at our institute as part of first-line therapy, mainly focusing on the safety and feasibility of mid-treatment patient transfer. Eighteen patients with newly diagnosed high-risk NB who received PBT between April 2010 and June 2016 were retrospectively analyzed for local control, outcomes, and toxicity. Survival (3-y overall survival 71%±11%; 3-y event-free survival 44%±12%) and local control rate (100%) were comparable with previous studies. Few acute adverse events were recorded, and all patients completed PBT without treatment delay. PBT for high-risk NB was safe and feasible for patients requiring mid-treatment interinstitutional transfer.

Accepted: 2017-12-12, 資料番号: SA1170295000

Objective: Proton beam therapy (PBT) may provide good local control for skull base chordoma and reduced toxicities, especially for pediatric patients. Methods: We evaluated the efficacy and safety of hyperfractionated high-dose PBT in6 pediatric patients with newly-diagnosed skull basechordoma who were treated with PBT at our institute from 2011 to 2015. The patients were 5 males and one female, and the median age was 9 years old (range: 5 - 13). All patients received surgery before PBT. The median period between surgery and PBT was 57 days (range: 34 - 129 days). The treatment dose was 78.4 GyE in 56 fractions (twice per day). Results: All patients received PBT without severe acute toxicity. The median follow-up period was 27 months (range: 21 - 71 months). At the last follow-up, all patients were alive and all tumors were well controlled. Acute and late toxicities were generally acceptable, with only grade 1 and 2 events. Late toxicities included growth hormone abnormality and cortical hormone abnormality. One patient needed growth hormone and cortical hormone replacement therapy. Conclusion: Although the number of pediatric patients was small, our overall findings in the 6 cases indicate that hyperfractionated high-dose PBT is safe and effective for pediatric patients with skull base chordoma.

A scanning electron microscope transition edge sensor has been developed to analyze the minor or trace constituents contained in a bulk sample and small particles on the sample under a low accelerating voltage (typically

Introduction: The aim of this study was to observe an inhibition of bone resorption and osteoclastogenesis by iguratimod (IGU, T-614), a disease-modifying anti-rheumatic drug, using adjuvant-induced arthritis (AIA) rats and receptor activator of nuclear factor kappa-B ligand (RANKL)-stimulated RAW264.7 cells. Methods: The bone mineral density and 3D morphometric parameters of hind paws in AIA rats were measured using micro computed tomography (μCT) imaging. The activity of osteoclast cells was estimated based on tartrate-resistant acid phosphatase (TRAP) staining in specimens from the rats. In vitro TRAP activity was investigated using RANKL-stimulated RAW264.7 cells. The amount of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) protein was measured by western blot analysis. The expression of Nfatc1, its regulator genes, its upstream factors, and osteoclast-functional genes were investigated. Results: In addition to the suppression of bone resorption and lesions of bone trabeculae of AIA rats, IGU significantly decreased the number of TRAP-positive cells in the calcaneal bones. Moreover, this drug inhibited the differentiation of RANKL-stimulated RAW264.7 cells into osteoclasts, which were identified morphologically and functionally. IGU decreased the amount of NFATc1 protein and improved the altered expression of NFATc1-associated genes and osteoclast-functional genes. Conclusions: IGU suppressed osteoclastogenesis and bone resorption via the RANKL-NFATc1 pathway, suggesting such effect would be expected in clinical use.

Accepted: 2015-06-18, 資料番号: SA1150096000

SUMMARY A four-pixel-array superconducting transition-edge sensor (TES) microcalorimeter with a mushroom-shaped absorber was fabricated for the energy dispersive spectroscopy performed on a transmission electron microscope. The TES consists of a bilayer of Au/ Ti with either a 50nm or 120-nm thickness. The absorber of 5.0 � m thick is made from a Au layer and its stem is deposited in the center of the TES surface. A Ta2O5 insulating layer of 100-nm thickness is inserted between the overhang region of the absorber and the TES surface. A selected pixel of the TES microcalorimeter was operated for the detection of Np L X-rays emitted from an 241 Am source. A response of the TES microcalorimeter to L X-rays was obtained by analyzing detection signal pulses with using the optimal filter method. An energy resolution was obtained to be 33eV of the full width at half maximum value at 17.751keV of Np L� 1 considering its natural width of 13.4eV. Response to L X-rays emitted from a mixture source of 238 Pu, 239 Pu and 241 Am was obtained by operating the selected pixel of the TES

Patients with rheumatoid arthritis experience nociceptive as well as neuropathic pain. The effect of iguratimod (IGU), a disease-modifying anti-rheumatic drug, on neuropathic pain in a rat model of chronic constriction injury (CCI) was examined in this study. CCI was induced by making four ligations on the left sciatic nerve. Rats with stable signs of static allodynia were selected 2 weeks after the surgery and drug treatments were started (day 0). The test drugs were orally administered once daily for 15 days. The threshold of mechanical pain response in the hind paw was evaluated by the von Frey hair test in a blinded manner. To observe histological changes in the spinal cord, the L4 region was subjected to immunohistochemical analysis for the detection of microglial cells. IGU showed an anti-allodynic effect on CCI-induced neuropathic pain at days 6 and 14, but not at 90 min after the first administration of IGU. This effect of IGU was observed until day 21. Furthermore, IGU decreased the number of Iba-1-positive cells, which had been increased at the ipsilateral side of the dorsal horn by CCI. These results suggest that IGU suppresses neuropathic pain via a different mechanism from that of current therapeutics.

[Objectives] The combined effects of a new antirheumatic drug, iguratimod (IGU) with antitumor necrosis factor (TNF)α antibody (aTNFAb) were examined in two mouse models of arthritis. [Methods] In collagen-induced arthritis (CIA) model, arthritis was induced by immunization with type II collagen on day 0 and 21. IGU was orally administrated once daily and aTNFAb was intraperitoneally injected twice a week from day 25 to day 34. In glucose-6-phosphate isomerase (GPI)-induced arthritis model, arthritis was induced by immunization with recombinant GPI on day 0 and the treatments were started on day 5. IGU was orally administrated daily and aTNFAb was intravenously injected every other day to day 14. Efficacy was evaluated using arthritis scores, articular destruction scores, and blood biochemical analyses. [Results] In the CIA model, the combination of IGU and aTNFAb significantly inhibited the arthritis and articular destruction more effectively than as monotherapies. Serum interleukin (IL)-1β and IL-6 levels were also reduced significantly with combined treatment. The decline in serum levels of cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase (MMP)3 was significantly enhanced with the IGU/aTNFAb combination. In the GPI-induced arthritis model, IGU and aTNFAb lowered the arthritis scores and the combination of both treatments showed a significant effect compared with IGU alone. Regarding anti-GPI titers on day 14, IGU and/or aTNFAb showed no significant effect. [Conclusion] In the two mouse models, the combination of IGU and aTNFAb showed greater benefit than either monotherapy, suggesting such combination therapy would be effective in clinical use.

An energy dispersive spectrometer with a superconducting transition edge sensor (TES) microcalorimeter mounted on a scanning transmission electron microscope (STEM) has been developed to improve the accuracy of nanoscale material analysis. Because of the magnetic field generated by the STEM objective lens, a TES microcalorimeter cannot be placed in a STEM column. Therefore, a polycapillary optics is used for collecting X-rays emitted by a STEM specimen on the TES microcalorimeter. The counting rate of 300 cps was insufficient for a practical application to the STEM. To achieve the counting rate larger than 5000 cps, we are now conducting development of a 64-pixel TES microcalorimeter system operating on the STEM. We developed a new polycapillary optics for a 64-pixel TES microcalorimeter with using a X-ray transmission simulation model that we made. We performed energy spectrum measurements of X-rays transmitted by the fabricated new polycapillary optics for evaluating the X-ray transmission characteristics.

Iguratimod (IGU), a disease-modifying antirheumatic drug launched in September 2012, has been reported to carry a risk of severe hemorrhages through a suspected interaction with warfarin (WF) in the all-case surveillance and early postmarketing-phase vigilance. To elucidate possible mechanisms of adverse interaction between IGU and WF, we analyzed the effects of IGU on the pharmacodynamics and pharmacokinetics of WF in rats. IGU was orally administered to male Wistar rats once daily for 5 d at 10 or 30 mg/kg in combination with WF at an oral dose of 0.25 mg/kg. Coadministration of IGU 30 mg/kg enhanced the anticoagulant activity of WF; prolonged blood coagulation time (prothrombin time and activated partial thromboplastin time) and decreased levels of vitamin K (VK)-dependent blood coagulation factors (II, VII, IX, and X) were observed. On the other hand, the pharmacokinetic parameters of WF including maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 to 24 h (AUC0-24 h) were not affected by the combination with IGU. IGU alone did not change blood coagulation time at doses up to 100 mg/kg, while VK-dependent blood coagulation factors decreased slightly at 30 and 100 mg/kg. These results suggest that the pharmacodynamic effect of IGU on VK-dependent blood coagulation factors is involved in the mechanism of drug-drug interaction of IGU with WF.

The application of light-weight drive technology into the lithography stage has been the current state of art because of minimization of power loss. The purpose of this article is to point out the so-called, "surface stage" which is composed of Lorentz forced 3 DOF (Degree Of Freedom) planar motor (x, y and theta z), air levitation (bearing) system and motor cooling system, is the most balanced concept for the next generation lithography through the verification of each component by manufacturing simple parts and test stand. This paper presents the design method and procedure, and experimental results of the air levitated surface stage which was conducted several years ago, however the author is convinced that the results are enough to adapt various developments of precision machining tool.

The capability of an analysis system consisting of a low voltage scanning electron microscope, which is superior in spatial resolution and surface sensitivity, and a superconducting transition edge sensor (TES), which is under development, has been evaluated. The analysis system equipped with the TES, which has a superior energy resolution by about an order of magnitude to a conventional energy dispersive x-ray spectrometer (EDS), is useful for chemical state analysis that makes use of the strength ratio of characteristic x-rays of the same series. Elemental segregation in microstructures, whose size is several tens of nanometers as for simple energy-window maps or around 10 nm as for point analysis, is also detectable. It is expected that precise distribution of minor elements, which overlap with major elements in conventional EDS spectra, and chemical state maps of specific elements can be evaluated if the data processing of spectral imaging is incorporated into the system.

We have developed a Transition Edge Sensor (TES) – Energy Dispersive Spectroscopy (EDS) for Transmission Electron Microscope (TEM) based on a dilution refrigerator. The dilution refrigerator was cooled by liquid helium (L-He), which was supplied from an L-He container separated from the dilution refrigerator. We adopted the hybrid magnetic shields combining a permalloy shield and a NbTi/Nb/Cu superconducting shield to operate the TEM–TES system under a magnetic field of 200 mT. The permalloy shield was used to prevent the ambient magnetic field until the NbTi superconducting shield cooled from room temperature (RT) to 2 K. The critical magnetic field was 220 mT for the TES change from a superconducting state to a normal state. The SQUID – current vs. bias current curve, under the condition that the snout was inserted in the TEM, was equal to the curve of the snout that was out of the TEM. The C (0 0 2) planes could be observed at 120 kV under the condition the snout was inserted in the TEM.

Accepted: 2009-08-04, 資料番号: SA1000816000

The Transition Edge Sensor (TES)-Energy Dispersive Spectrometer (EDS) is an X-ray detector with high-energy resolution (12.8eV). The TES can be mounted to a scanning electron microscope (SEM). The TES-EDS is based on a cryogen-free dilution refrigerator. The high-energy resolution enables analysis of the distribution of various elements in samples under low acceleration voltage (typically under 5keV) by using K-lines of light elements and M lines of heavy elements. For example, the energy of the arsenic L line differs from the magnesium K line by 28eV. When used to analyze the spore of the Pteris vittata L plant, the TES-EDS clearly reveals a different distribution of As and Mg in the micro region of the plant. The TES-EDS with SEM yields detailed information about the distribution of multi-elements in a sample.

At first, I explain some key points and difficulty of lithography tool design, issues that should be overcome during the development and requirements for stages in lithography tool in this paper. Then, I have ascertained a limit of static-pressure air bearing with differential pumping mechanism for vacuum application, for instance EUVL(Extreme Ultra Violet Lithography tool) by manufacturing so-called the “vacuum compatible” 1-axis air bearing and verifying the performance by comparing with equivalent model simulation. Finally, one of MAGLEV(MAGnetic LEVitated) stage concepts is proposed instead of common AIRLEV(AIR LEVitated) stage by seriously considering a high throughput for mass production. I simultaneously contribute 2nd paper, “Development of 6DOF Magnetic Levitation Stage for Lithography Tool -Proof Of Concept (Second Report)-“ which is a sequel to this paper.

A microcalorimeter with the superconducting transition edge sensor (TES) with a Au absorber of 5.0 μm thick was fabricated for the energy dispersive measurement of LX-ray photons emitted from transuranium elements. The TES microcalorimeter and a superconducting quantum interference device (SQUID) amplifier chips were cooled by operating a compact 3He-4He dilution refrigerator without consuming liquid helium by loading a Gifford-McMahon (GM) cooler. Since the cold stages of the GM cooler are tightly coupled to the heat exchangers of the dilution refrigerator, the TES and SQUID chips suffered from mechanical vibrations induced by a reciprocating motion of the displacer of the GM cooler. Detection signals of LX-ray photons emitted from an 241Am source were observed by operating the TES microcalorimeter in severe noise environment induced by mechanical vibrations.

We previously demonstrated that activation of sensory neurons increases endothelial prostaglandin I 2 (PGI 2 ) production by releasing calcitonin gene-related peptide (CGRP). Since PGI 2 reduces post-traumatic spinal cord injury (SCI) by inhibiting tumor necrosis factor (TNF) production, activation of sensory neurons in the spinal cord tissue may ameliorate spinal cord injury. This study examines these possibilities using rat models of compression trauma-induced SCI. Both SB366791, a specific vanilloid receptor antagonist, and CGRP (8-37), a CGRP receptor antagonist, significantly inhibited trauma-induced increases in spinal cord tissue 6-keto-PGF 1α levels. SB366791, CGRP (8-37) and indomethacin (IM) enhanced increases in spinal cord tissue TNF levels at 2 h after trauma and exacerbated motor disturbances. Administration of CGRP significantly reduced motor disturbances and inhibited increases in spinal cord tissue TNF levels through enhancement of increases in tissue levels of 6-keto-PGF 1α . These observations strongly suggest that activation of sensory neurons might ameliorate compression trauma-induced SCI, inhibiting TNF production through enhancement of endothelial PGI 2 production. Thus, although the spinal cord sensory neurons function as nociceptive neurons, they could also be critically involved in the cytoprotective system that attenuates SCI development and, thus, pharmacological stimulation of spinal cord sensory neurons might contribute to reduce spinal cord injury.

Sadatomi and Kawahara invented a multi-fluids mixer which is categorized as a twin-fluid type but have a merit of water suction type. The mixer is usable to generate micro- bubbles, etc. besides mists, fine droplets. In the mists generation, pressurized air alone is supplied because water can be sucked automatically by a negative pressure arisen downstream from the orifice in the mixer. The objective of the present study is to compare the performance between the above twin-fluid type atomizer and a common single-fluid swirl type atomizer studied in the present experiments. The comparison results showed that the twin-fluid type was superior to the singe-swirl type in the performance of CO2 adsorption by the mists. The CO2 adsorption rate by the twin-fluid type was about twice. Such results on the experiments and the comparisons are described in this paper. Keywords—atomizer, twin- and single-fluid types, hydraulic performance, CO2 adsorption

Iguratimod (IGU), a small-molecule compound, was developed as a disease-modifying antirheumatic drug in Japan. The pharmacological studies showed that inhibition of the production of cytokines and immunoglobulins mainly contributes to its improvement effect on animal arthritis models. The first clinical study of IGU in Japanese patients with rheumatoid arthritis was started in 1992 and Phase III studies were started in 1998. From the results of Phase II studies, a dose-escalating regimen was recommended to relieve the side effects. In a double-blind study comparing the efficacy and safety of the drug with those of placebo and salazosulfapyridine, it was confirmed that IGU was superior to placebo and was not inferior to salazosulfapyridine. Furthermore, a double-blind controlled trial of IGU in combination with methotrexate revealed an efficacious and manageable safety profile. IGU would be widely used as a new option for rheumatoid arthritis treatment and combination drug with methotrexate.

crews become more sophisticated. A marked increase in the recent volume of emergency calls is another issue of concern. Currently, private services for transportation of non-acute or minor injury/illness have been introduced in some areas, and dispatch protocols to triage 199 calls are in development., Emergency medical services are provided by the fire defense headquarter of the local government in Japan. We have a one-tiered EMS system. The ambulance is staffed by three crews trained in rescue, stabilization, transportation, and advanced care of traumatic and medical emergencies. There are three levels of care provided by ambulance personnel including a basic-level ambulance crew (First Aid Class one, FAC-1), a second level (Standard First Aid Class, SFAC), and the highest level (Emergency Life Saving Technician, ELST). ELSTs are trained in all aspects of BLS and part of ALS procedures relevant to prehospital emergency care. Further development of an effective medical control system is imperative as the activities of ambulance

The authors examined whether a serum pepsinogen test (SPT) based on the combination of the serum pepsinogen I level and pepsinogen I/II ratio is a good predictor of gastric cancer occurrence in a general Japanese population. A total of 2,446 subjects aged � 40 years were classified into negative, positive, and strong-positive SPT groups and were followed prospectively for 14 years (1988–2002). Compared with that for the negative SPT group (26 men, 10 women), gastric cancer incidence increased significantly for both men (n ¼ 17; age-adjusted hazard ratio ¼ 4.56, 95% confidence interval: 2.42, 8.60) and women (n ¼ 6; age-adjusted hazard ratio ¼ 5.84, 95% confidence interval: 2.00, 17.11) in the strong-positive SPT group. It was also significantly higher in the positive SPT group for men (n ¼ 23; age-adjusted hazard ratio ¼ 3.91, 95% confidence interval: 2.23, 6.86). These associations did not attenuate even after adjustment for other comprehensive risk factors. Stratified analysis revealed significant associations between the SPT and development of intestinal-type gastric cancer as well as of cancer in both Helicobacter pylori–negative and –positive subjects. These findings suggest that the SPT can serve as a predictor of intestinal-type gastric cancer, irrespective of H. pylori infection. cohort studies; gastritis, atrophic; Helicobacter pylori; pepsinogens; stomach neoplasms

The temporal development of shock waves generated by pulsed streamer discharges in water was observed by means of time-resolved imaging based on the laser Schlieren method. The pressure of these shock waves was calculated using the Hugoniot equations, which use the relationship between the shock wave pressure and shock wave velocity. The streamer discharges were generated by applying pulsed positive voltages to a needle electrode. The measurements indicate that pressures exceeding 1 GPa occur in the vicinity of the streamer discharges.

After the enactment of Japan's Soil Contamination Countermeasures Law in 2002, landowners, particularly private firms and enterprises, were obligated to shoulder a new risk. Compared with other countries, Japan's implementing of government regulations and providing fiscal support in this field have been too little and too late. Consequently, Japan should promptly consider necessary means of implementing environmental protection measures, information disclosure, and a system of financial support.The purpose of this research is to verify practical measures that can be taken in the future to address the issue of contaminated areas in Japan. In order to survey and summarize the overall situation regarding soil-contaminated areas, we relied on the experience in Germany, where the economic situation is similar to that in Japan. With reference to a case study conducted in Germany, we analyzed practical measures to achieve purification, considered the influence of the central government and municipalities, and characterized the difficulty of practical implementation.This paper is a revised version of the theme on which it reported at the international Meeting PRSCO (The 19th Pacific Regional Science Conference) held by the Nihon University College of Economics Tokyo on 24 July 2005.To our regret, it became difficult to continue this research due to the sudden death of the superintendence Prof. Keiichi Tanaka, who headed the research. Therefore, this research project ended with a temporary respondent report.JEL Classification: H20, Q51, Q58

When a scanning electron microscope (SEM) is used for analysis, a low acceleration voltage must be used to reduce damage to the sample and to obtain information near the sample surface. Here, a microcalorimeter energy dispersive spectrometer (EDS) system without external cryogen was developed to analyze material samples under low acceleration voltages (

To examine secular trends in the incidence and mortality of gastric cancer in a Japanese community, Hisayama, we established three study-cohorts of Hisayama residents aged >40 years in 1961 (1637 subjects), 1974 (2054), and 1988 (2602). Each cohort was followed up for ten years. The age-standardized mortality from gastric cancer significantly decreased from 2.4 per 1000 person-years in the first cohort to 0.8 in the third cohort for men, and from 1.0 to 0.2, respectively, for women (p < 0.01 for trend in both sexes). The five-year survival rate after gastric cancer significantly improved from the first (32.6%) to the third cohort (73.0%, p < 0.01) for men and from 43.2% to 72.3% (p < 0.05), respectively, for women. The age-standardized incidence of cancer in men was not different among the cohorts (4.3 per 1000 person-years in the first, 5.0 in the second, and 4.9 in the third cohort), while it decreased significantly in women (2.0, 1.8, and 1.2, respectively, p < 0.01 for trend). In conclusion, our findings suggest that in a Japanese population, the mortality from gastric cancer declined during the past 40 years, due mainly to the improvement of survival in both sexes and a decrease in the incidence for women.

OBJECTIVE—Several studies have shown associations between diabetes and various types of cancer other than gastric cancer. The aim of this cohort study was to evaluate the impact of fasting plasma glucose (FPG) levels on gastric cancer occurrence. RESEARCH DESIGN AND METHODS—A total of 2,466 Japanese subjects aged ≥40 years were stratified into three groups according to FPG tertiles (5.8 mmol/l, high FPG) and followed up prospectively for 9 years. RESULTS—During the follow-up, 66 subjects experienced gastric cancer. In men, the age-adjusted incidences were significantly higher in the modest-FPG (7.0 per 1,000 person-years, P < 0.05) and high-FPG (7.2, P < 0.05) groups than in the low-FPG group (2.2). In women, the high-FPG group also had a significantly higher age-adjusted incidence of gastric cancer compared with the low-FPG group (2.5 vs. 0.8, P < 0.05). The multivariate analysis with Cox’s proportional hazards model revealed that the risks of gastric cancer in the modest-FPG (relative risk [RR] 2.3 [95% CI 1.1–5.0]) and high-FPG (3.1 [1.5–6.4]) groups were significantly higher than that in the low-FPG group, even after adjusting for other comprehensive risk factors, including Helicobacter pylori status, smoking, and dietary factors. However, this FPG-cancer association was observed only among H. pylori–seropositive subjects. CONCLUSIONS—Our findings suggest that a modest increase in FPG is a risk factor for gastric cancer and that hyperglycemia is a possible cofactor increasing the risk posed by Helicobacter pylori infection.

著者人数：22名, 資料番号: SA1001095000

Background and Purpose— The slowdown of a steeply declining trend in cardiovascular mortality has been reported in Japan, but precise reasons for this trend are uncertain. Methods— We established 3 study cohorts of Hisayama residents aged ≥40 years without a history of stroke or myocardial infarction in 1961 (1618 subjects, first cohort), 1974 (2038 subjects, second cohort), and 1988 (2637 subjects, third cohort). We followed up with each cohort for 12 years, comparing the incidence, mortality, and survival rate of cardiovascular disease. Results— The age-adjusted incidence of cerebral infarction significantly declined by 37% for men and by 32% for women from the first to the second cohort. It continued to decline by 29% for men, but the decline decelerated for women in the third cohort. The incidence of cerebral hemorrhage steeply declined by 61% from the first to the second cohort in men only, while it was sustained for both sexes in the third cohort. Stroke mortality continuously declined as a result of these incidence changes and significant improvement of survival. In contrast, the incidence and mortality rate of coronary heart disease were unchanged except for the increasing incidence in the elderly. The prevalence of severe hypertension and current smoking significantly decreased, while that of glucose intolerance, hypercholesterolemia, and obesity greatly increased among the cohorts. Conclusions— Our data suggest that the decline in stroke incidence is slowing down and that the incidence of coronary heart disease has been increasing in the elderly in recent years. Insufficient control of hypertension and the increase in metabolic disorders may contribute to these trends.

Necrotizing fasciitis (NF) is an acute, potentially lethal soft-tissue infection accompanied by distinct clinical features such as exquisite pain, local heat, swelling, flare, and bubbles in the affected regions. The diagnosis is confirmed upon isolation of causative organisms and pathological findings of the necrosis of the fascias. In most cases, patients with NF suffer systemic symptoms caused by sepsis, such as shock, DIC and MOF when they are referred to tertiary medical facilities. Mortality is usually due to delayed diagnosis. Therefore, early diagnosis and prompt treatment are the key to reducing mortality and morbidity of patients with NF. We present six patients with NF who required intensive care at our center. Subjects consisted of four men and two women, age ranging from 56 to 70 years, with an average age of 62.5 years. The affected regions included one upper limb (one patient), one lower limb (two patients), one upper limb and torso (two patients), and one lower limb and torso (one patient). All of the patients had underlying diseases such as diabetes mellitus, and cirrhosis of the liver. Most of the patients deteriorated rapidly, two of them underwent surgical treatment, and five died in spite of aggressive treatment.

症例は67歳,女性.平成6年9月21日,右乳癌にて胸筋温存乳房切除術施行されている.乳頭腺管癌および硬癌, T2aN0M0, Stage IIであった.平成9年4月,骨転移を認め,化学療法(CMF)を平成13年5月まで,計6クール施行,長期PRを維持していたが,肝転移を認めたため,平成13年5月～平成14年12月までDocetaxelを少量分割投与にて計18クール施行し, CRを得ていた.平成14年10月から肛門痛と頑固な便秘が病苦となり,注腸造影を施行したところ,下部直腸に全周性の狭窄を認めた.下部消化管内視鏡では,歯状線から2 cm口側より4型の全周性の狭窄と粘膜のびらんを認めた.生検による病理組織検査において低分化型腺癌を認めた.平成14年12月14日,腹会陰式直腸切断術施行した.病理組織学的に特殊染色GCDFP (15) (+), HMFG2 (+),ラクトフェリン(+), ALA (+), ER (3+), PgR (+)であり,乳癌の直腸転移と診断した.またHER-2 (2+)であったため,平成15年1月よりPaclitaxel, Trastuzumabによる化学療法を施行中である.進行乳癌の消化管転移の報告は少なく,特に下部直腸の転移腸管の切除例は非常に稀である.若干の文献的考察とともに報告する.

症例は72歳,男性.平成12年9月15日,吐血にて当院受診.上部内視鏡および消化管造影検査にて胃体中部の進行胃癌と診断し,胃全摘Roux-en-Y吻合(D 2)施行した.切除標本では胃体中部小彎前壁に4.8×3.3×1.6cmの粘膜下腫瘍を認め,さらにこの粘膜下腫瘍上にかかる形で, 4.7×4.0cmのIIa集簇型病変を認めた.病理組織学的所見は粘膜下腫瘍部分が免疫組織化学的にgastrointestinal stromal tumor (GIST)と診断され, IIa集簇型病変は深達度Smの中分化型早期胃癌と診断された.近年GISTの概念が一般的となり,消化管上皮性腫瘍との合併例の報告が散見されてきているが,今回われわれは早期胃癌と胃GISTが同一部位に合併した稀な1例を経験したので報告する.

Recent epidemiological studies provide strong support for the hypothesis that the daily consumption of fruits is effective for preventing such diseases as cancer, hypertension, and cardiovascular disease. The value of fruit is considered to be equivalent to that of vegetables by health-conscious American and European consumers concerned with preventing such diseases. Health authorities in the USA recommend a diet of five servings of fruit and vegetables each day. However, in Japan, fruit is given less attention than vegetables by the average consumer concerned with nutrition and disease prevention. The consumption of fruit in Japan has recently decreased or remained at the same level. It is possible that this may be due to a general mistaken connection between fruit consumption and the risks of diabetes, hyperlipidemia, and obesity. Youthful consumers are especially susceptible to this misunderstanding, and their consumption of fruit has recently been decreasing annually. Fruit is a significant source of vitamins, minerals, and dietary fiber. Furthermore, fruit contains numerous bioactive substances, such as carotenoids and flavonoids, which play an important role in protecting from oxidative damage. Recent epidemiological studies about the relationship of fruit consumption and chronic diseases are reviewed.

A superconducting quantum interference device (SQUID) amplifier has been developed as a current detector with both high-current resolution and broad bandwidth for a transition edge sensor calorimeter. The amplifier is a two stage SQUID (TSS) that consists of an input-SQUID with a 38-turn input coil and a 100-serial SQUID array (100-SSA) output, and has been integrated on a 3 /spl times/ 3 mm Si chip using Nb thin film fabrication technology. It is designed to increase the amplifier gain and maintain matching with the parameters of the calorimeter. To avoid flux trapping in the SSA, the washer coil of the dc-SQUIDs in the SSA was made with a narrow line width of 17.5 /spl mu/m. We experimentally confirmed that the designed output voltage was achieved using a one-layer p-metal magnetic shield tube in the earth's magnetic field. The performance of the shielded TSS amplifier was evaluated in liquid helium. The TSS amplifier had a gain of 10 kV/A and an impedance of 0.07 /spl Omega/ at 100 kHz. When a flux locked loop circuit was used to drive the amplifier, a current resolution of 1 pA//spl radic/Hz and a rise time of 1 /spl mu/s were achieved.

Insulin resistance may be a factor in the etiology of hypertension, and habitual alcohol intake may modify this relationship. We prospectively examined this hypothesis in 1,133 nonhypertensive, nondiabetic Japanese subjects, aged 40–79 years. Alcohol drinkers were more frequent among men than women at baseline (57.7 vs. 8.2%). The age-adjusted incidence of hypertension significantly increased with the elevating baseline insulin levels in women (P = .003 for trend), but not in men. The age- and sex-adjusted insulin levels and insulin resistance index decreased with elevating alcohol intake, while fasting glucose levels remained unchanged, suggesting that alcohol improves insulin sensitivity. Among nondrinkers, the age-adjusted incidence of hypertension significantly increased with elevating insulin tertiles in both sexes (P = .048 and .002 for trend in men and women, respectively), but not among drinkers. Our findings suggest a close association between insulin resistance and the incidence of hypertension in Japanese. However, alcohol modified and reduced this relationship.

Pulmonary embolism (PE) due to deep vein thrombosis (DVT) remains the most serious complication in acute spinal cord injury (SCI). The incidence of PE has been reported as relatively low in Japan, however it can be lethal if it occurs. We experienced two similar cases of fatal PE after SCI. Case 1 was a 44-year-old male with BMI of 29.4. He was treated for schizophrenia on an out-patient basis. He attempted suicide by leaping from a height and suffered polytrauma including bursting fracture of the third lumbar vertebra, for which posterior lateral fixation of the spine was performed. Seventeen days after surgery, he fell into cardiopulmonary arrest due to suspected PE and died in spite of aggressive cardiopulmonary resuscitation. Case 2 was a 34-year-old male with BMI of 35.5. He had a very similar history of mental disorder, mechanisms of injury and surgical procedures as case 1. He suddenly collapsed on the 27th postoperative day and was diagnosed as massive PE by arteriography. Thrombolytic therapy and catheter-tip embolectomy were immediately performed without success. For these two ceses, anticoagulation was not instituted. There are several factors that predisposed these patients to PE; trauma, obesity and postsurgical status for spine fracture. Prevention of DVT is the key strategy against PE. Therefore, Preventive measures including routine use of anticoagulants or placement of filter devices for these high-risk group patients should be considered.