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The links between gambling and criminal offenses have been frequently reported, but the pathways from gambling to a particular offense have not. Our study applied a pathways model to predict participants' income-generating, drug-related, and violent offenses stemming from their craving for gambling. The participants were 332 male inmates in a Japanese local prison. They answered questionnaires on gambling behavior, alcohol addiction, Internet addiction, impulsivity, and psychopathy. Their official records with information on their current offense, sentence length, number of imprisonments, and length of education were also analyzed. The results show that 38.55% (n = 128) of the participants had a probable gambling disorder, a rate of problem gambling at least four times higher than that among the general Japanese population. Furthermore, their craving for gambling predicted their income-generating offenses, but not their drug-related and violent offenses. Their craving for gambling can thus be linked to their financial issues, rather than their emotional and impulsive issues. The pathways model explained the path not only from addiction/psychopathy to gambling, but also from gambling to committing an income-generating offense.

Petit-High Pressure Carbon Dioxide (p-HPCD) is a promising nonthermal technology for foods pasteurization. Cluster analysis of gene expression profiles of Saccharomyces cerevisiae exposed to various stresses exhibited that gene expression profile for p-HPCD stress (0.5 MPa, 25 °C) was grouped into a cluster including profiles for Sodium Dodecyl Sulfate and Roundup herbicide. Both are detergents that can disorder membrane structurally and functionally, which suggests that cell membrane may be a target of p-HPCD stress to cause cell growth inhibition. Through metabolomic analysis, amount of S-Adenosylmethionine (AdoMet) that is used as methyl donor to participate in phosphatidylcholine synthesis via phosphatidylethanolamine (PE) methylation pathway, was increased after p-HPCD treatment for 2 h. The key gene OPI3 encoding phospholipid methyltransferase that catalyzes the last two steps in PE methylation pathway was confirmed significantly induced by RT-PCR. Transcriptional expression of genes (MET13, MET16, MET10, MET17, MET6 and SAM2) related to AdoMet biosynthesis was also significantly induced. Choline as the PC precursor and ethanolamine as PE precursor in Kennedy pathway were also found increased under p-HPCD condition. We also found that amounts of most of amino acids involving protein synthesis were found decreased after p-HPCD treatment for 2 h. Moreover, morphological changes on cell surface were observed by scanning electron microscope. In conclusion, the effects of p-HPCD stress on cell membrane appear to be a very likely cause of yeast growth inhibition and the enhancement of PC synthesis could contribute to maintain optimum structure and functions of cell membrane and improve cell resistance to inactivation.

It has been demonstrated that pasteurized effect on microorganisms of petit-high pressure carbon dioxide (p-HPCD) with long time treatment is similar to the effect of HPCD with short time treatment. The ‘petit-high pressure’ refers to a pressure of 1.5–13 atm (standard atmosphere). After 0.5 MPa of CO2 at 25°C for 2 h treatment, specific growth rate of yeast cells in the logarithm phase was decreased by 50% approximately. Under this condition, our study analyzed transcriptional responses of Saccharomyces cerevisiae through the functional genomic approach. Transcription of 837 open reading frames (ORFs) was altered relative to cells without treatment and 476 ORFs were induced after p-HPCD treatment. These selected genes were then categorized by function of gene product using the Munich Information Centre for Protein Sequences database. Genes involved in ‘metabolism of the urea cycle’ were found to be significantly induced. This enhanced metabolic process could help to remove redundant HCO3− in cell...

Social reintegration has been known to protect against recidivism, but its effects against drug-use relapse have previously remained unclear. To address this gap, the present study sampled 196 inmates imprisoned for drug-related offenses in Japan. We examined the protective effects of a social reintegration (parole) program against recidivism and drug-use relapse using a 4-year prospective design. During the 4-year follow up, 79 (40.3 %) of the participants reoffended and 61 (31.1 %) relapsed into drug use. The results suggest that the parole program was significantly associated with a decreased risk of recidivism, even if participants’ age, sentence length, number of prison terms, educational levels, and gang membership were controlled for. However, the effects of the parole program on drug relapse disappeared when the above variables were controlled for. To decrease the risk of relapse, drug-related inmates may need both prosocial communities and rehabilitative environments. The Japanese criminal justice system needs to introduce drug treatment courts for drug users.

In this article we present a relevant strategy for a non-trivial time-programmed release of water-soluble macromolecules from biocompatible μ-containers. The system is based on self-scrolled chitosan acetate (CA) fibers, encapsulated in a poly(dimethylsiloxane) matrix. Mass transfer between a fiber and the external environment takes place via the only opened extremity of the fiber. Fluoroscein isocyanate dextran (FID) is initially deposited at the inner surface of the CA fiber according to a programmed pattern. The FID molecules became mobile after the arriving of the swelling front, which propagates along the fiber's axis upon the immersion of the system in aqueous solution. Diffusion of the macromolecules into the environment is enabled by the open-tube geometry of the swollen part of the fiber, while a programmed kinetics of the drug release is due to patterning of the polymer film prior to rolling. The release of the macromolecules can be retarded by a few hours according to the placement of the FID spot with respect to the fibers orifice. A pulsatile release kinetics is demonstrated for a discrete pattern. A few millimeter spacing of the FID spots results in a few hours time interval between the release impulses. Random walk model is plugged in the effective diffusion coefficient for Fick's law and the release kinetics are simulated.

We measured step velocity Vstep in the direction of two dimensional islands on the {110} faces of tetragonal lysozyme crystals under high pressure, and calculated step kinetic coefficients βstep. Vstep and βstep decreased with increasing pressure. The decrease in βstep indicates the increase in activation energy of the crystallization εkink or the mean distance between kinks on the step λ.

Equilibrium temperatures, T e , of tetragonal hen egg-white lysozyme crystals were determined by in situ observation of apex regions formed by the (110), (110) and (101) faces of the crystals. We could precisely measure T e within 60 min, and with an error margin ±0.7 °C or less. This is largely because growth and dissolution can be detected more rapidly at the apex than at the steps at the center of the crystal faces.

The perpendicular fracture surface of a dried colloidal crystal with pillar-like grains, obtained by centrifugation of a dispersion of polystyrene particles, was observed using a scanning electron microscope. Many grain boundaries on the fracture surface were observed at the particle level. Most of the particles on the surface showed a face-centered cubic (FCC) array. Although some grains were single FCC ones, other FCC grains contained some stacking disorders. Most of the surface was covered with such grains, and the grain boundaries formed a mosaic-like pattern. From these results, we confirmed that the colloidal crystals obtained by centrifugation formed a bundle structure of pillar-like FCC grains. A fracture surface adjacent to the side wall of the growth cell was also observed. The surface was composed of several layers. In the uppermost layer closest to the wall, numerous point defects and mismatches of triangular lattices between the neighboring two-dimensional islands were observed. These mismatches and point defects probably generated several lattice defects in the crystal. Similar generation of lattice defects probably occurred at the bottom of the container or the growth front of the crystals. Screw dislocations were also found in the layers, although they were not observed frequently. From these results, it was concluded that two-dimensional nucleation growth and spiral growth probably occurred on the crystal-dispersion interfaces of colloidal crystals as well as on the surface of atomic crystals.

We measured the temperature dependence of the solubility, C e , of triclinic lysozyme crystals on temperature at two pressures (0.1 and 100 MPa) and five pHs (4.3, 4.4, 4.5, 4.6, and 4.7) by in situ observation of the morphological changes in the crystals. The solubility increased with increase in temperature and pressure. The enthalpies of dissolution (Δ H ) decreased with increase in pressure when we used the same 50 mM sodium acetate buffer solution (pH=4.5 at 0.1 MPa). The effects of pH on solubility were somehow complicated. Although the solubilities at pH 4.7 did not differ from those at pH 4.5, those at pH 4.3 were significantly larger than those at pH 4.5. Since the pH of an acetate buffer is known to decrease from 4.71 to 4.52 at 98.1 MPa and 25 °C [22] , the pH of the acetate buffer (pH 4.5 at 0.1 MPa) decreased to pH∼4.3 as pressure increased to 100 MPa. Thus, from the viewpoint of “constant pH”, Δ H increased with increase in pressure, since Δ H at pH 4.3 and 0.1 MPa was smaller than that at 100 MPa. This inconsistency is probably due to the change in the hydration state of the crystal and solution with decreasing pH (from 4.5 to 4.3).

The activation volume, Δ V ‡, of the solute incorporation process at the kink site of a glucose isomerase (GI) crystal was estimated using the pressure dependency of the step kinetic coefficient, βstep, and the three-dimensional nucleation rates J of GI crystals were analyzed using classical nucleation theory. Δ V ‡ took a negative value. The sticking parameter, s, for the addition of a GI tetramer to a critical nucleus drastically increased with increasing pressure. This was probably due to the decrease in the activation energy needed for the addition of the GI tetramer.

The effect of compressed unsaturated hydrocarbon gases on the growth of the yeast Saccharomyces cerevisiae was investigated by microcalorimetry. The growth thermograms showed that unsaturated hydrocarbon gases inhibited yeast growth. As an approach to determining the comparative toxicity of unsaturated hydrocarbon gases, we determined the 50% inhibitory pressure (IP 50 ) and the minimum inhibitory pressure (MIP). On the basis of the IP 50 and MIP values, the inhibitory potency of the gases increased in the order ethylene < propylene < 1-butene. Additionally, scanning electron microscopy showed that cells treated with unsaturated hydrocarbon gases were damaged, including invagination of the cell surface.

We studied the lethal action of compressed oxygen gas on yeast cells and discussed its application to the sterilization processing of sudachi juice. The yeast cells (Candida boidinii SYM-1) suspended in sudachi juice could be sterilized completely when treated under the following conditions: 5.0 MPa for 15 min at 30°C, 10.0 MPa for 5 min at 40°C, and 5.0 MPa for less than 1 min at 50°C. Sudachi juice was sterilized by the treatment at 50°C without loss of vitamin C content. The removal of dissolved oxygen in sudachi juice by nitrogen gas pressurization was examined. The direct pressurization of sudachi juice with nitrogen gas decreased the amount of dissolved oxygen in it. When sudachi juice was compressed directly with nitrogen gas, more oxygen could be eliminated by applying higher nitrogen gas pressure and by taking longer time. Repetition of pressurization and depressurization with nitrogen gas could shorten the time to remove oxygen.

三次元的な広がりをもったグレイン(結晶粒)をもつ密充填のコロイド結晶を制御して効率よく作製するため，比重の小さなポリスチレン粒子を遠心沈降濃縮した．その結果，0.1～1.0 mm の幅で 10 mm 程度の長さをもつ柱状のグレインの集合体からなる高粒子密度のコロイド結晶を 84 G(1 G=9.8 ms-1)の遠心加速度により，従来の自然沈降法よりも短い時間(1 週間)で作製できた．遠心機から取り出し た結晶は，単に逆さま(固液界面で分散液のほうに向かって 1 G の加速度がかかる状態)にすることで可逆的に溶解したことから，通常の結晶の高品質化技術を適用できる可能性が示唆された．また，遠心沈降法によって得られた高粒子密度(体積分率 φ～0.4)のコロイド結晶をゆっくり乾燥させることで，結晶構造を壊すことなく密充填の乾燥コロイド結晶を得ることができた．遠心沈降法によって得られるコロイド結晶の平均的なグレインサイズは，沈降速度を減少させることによって大きくなった．これは，沈降速度の減少により，セル底面において生成した結晶核が減少したことによると考えられる．

Addiction is serious problem that requires effective treatment. Previous studies support personalized feedback interventions (PFIs) as an effective treatment for drinking; however, the potential beneficial effects of this treatment on illegal drug use have not been explored. The present study examined the effects of PFIs in a sample of repetitive drug-related offenders. Participants were 50 repetitive drug-related offenders incarcerated in a Japanese prison. They were randomly assigned to the PFIs (n = 20) or control (n = 30) group. The PFIs group received six letters for 3 months, whereas the control group did not undergo any interventions. We defined relapse and recidivism as drug-related reoffending and reentering prison after release, respectively. In the 3.6-year follow-up analysis (range, 0.1–5.8 years), participants’ criminal records were examined, and results indicated a decreased risk of relapse and recidivism for the PFIs group relative to the control group, even when controlling for age, educational level, number of prison terms, and sentence length. Thus, our findings suggest that PFIs reduce the likelihood of relapse and recidivism in drug-related offenders.

Solubility of tetragonal lysozyme crystal was measured by using two different methods. The solubility measured by using growth rates of the crystal corresponded well to that measured by using change in the concentration of the supernatant of the solution. Our data also corresponded well to the data obtained by Sazaki et al. and Gray et al., while not to those obtained by Howard et al. and Rosenberger et al. The discrepancies are due to the difference in the principles of the methods. We also checked effects of different initial concentrations on the solubility. Contrary to previous reports, the solutions of the different initial concentrations did not reach equilibrium when their concentrations attained to a same value.

Microcalorimetry is a useful tool for monitoring the growth behavior of microorganisms. In this study, microcalorimetry was used to investigate the effects of nitrogen, air, oxygen, nitrous oxide, argon, and krypton at high pressure on the growth of the yeast Saccharomyces cerevisiae. Growth thermograms (metabolic heat vs. incubation time) were generated to estimate metabolic activity under compressed gases and to determine the 50% inhibitory pressure (IP50) and minimum inhibitory pressure (MIP), which are regarded as indices of the toxicity of compressed gases. Based on MIP values, the most toxic to the least toxic gases were found to be: O2 > N2O > air > Kr > N2 > Ar.

窒素ガス加圧によるスダチ果汁中の溶存酸素の除去について検討を行い, 以下の結果を得た.(1) スダチ果汁を窒素ガスで直接加圧すると, 加圧時間を長くすることで, スダチ果汁中の溶存酸素はより減少し, 圧力を上げることで, より多くの溶存酸素が除去できた.(2) スダチ果汁に対して, 窒素ガス加圧と除圧を繰り返すと, スダチ果汁中の溶存酸素は短時間で減少し, 30℃, 10MPaで30秒間加圧した後, 常圧に戻す処理を, 3回繰り返したところ, 溶存酸素量は1mg/l以下まで減少した. さらに, 処理回数を増やすごとに溶存酸素量は減少し, 20秒間を7回 (計2分20秒間) の処理では0.02mg/lと, 非常に低い濃度まで溶存酸素を除去することができた.(3) スダチ果汁の香りに及ぼす窒素ガス加圧の影響を官能検査で調べた結果, 30℃, 10MPaで1分間以下の条件 (20秒間×3, 30秒間×2, 1分間×1) では, 香りを保持したままスダチ果汁中の溶存酸素を除去することができた.(4) スダチ果汁の窒素ガス加圧処理は, スダチ果汁保存中の酸化を防止し, 長期保存による香りや色の品質低下を抑制する可能性がある.

In order to form active sites for grafting amino groups, a predominant elimination of fluorine atoms from fluoropolymers such as poly(tetrafluoroethylene), ethylene-co-tetrafluoroethylene co-polymer (ETFE) and poly(vinylidene fluoride) was carried out using the plasma irradiation technique, and the possibility that amino functional groups could be formed on the fluoropolymer surfaces was investigated. The NH3 plasma irradiation led to considerable elimination of fluorine atoms from the fluoropolymers, as well as grafting of nitrogen functionalities. The formation of nitrogen-containing groups was strongly influenced by the magnitude of the W/FM parameter, and the NH3 plasma operated at a low W/FM parameter of 79 MJ/kg was found to be preferable for the surface modification process. XPS spectra for the NH3 plasma-modified surfaces showed that the NH3 plasma attacked predominantly CF2—CF2 sequences rather than CH2—CH2 sequences in the ETFE polymer. The primary amino groups formed on the ETFE film surfaces w...

Hydrostatic pressure is a useful parameter to control protein crystallization. One can change the solubility of protein crystals quickly by changing pressure. Information about the hydration of the specific surfaces of protein molecules can be obtained from the pressure dependency of solubility. When a protein molecule is hydrophobic or when its molecular volume in a solution is significantly larger than that in a crystal, applying high pressure is expected to be an effective method to promote crystallization. Pressure also affects the growth kinetics of protein crystals. Dependency of a growth rate on a driving force for crystallization was measured on typical proteins and analyzed using a two-dimensional nucleation growth model of a poly-nuclei type. High-pressure effects on growth kinetics could be explained by changes in a surface free energy, an activation energy and an average distance between kinks. Common understanding, however, has not yet been obtained for growth kinetics.

酵母に及ぼす加圧酸素ガスの致死作用とスダチ果汁の殺菌処理への応用について検討を行い,以下の結果を得た.(1) YPD培地に懸濁した酵母(Saccharomyces cerevisiae IFO 10149)を酸素ガスで直接加圧すると,生菌数が減少し,生存率は圧力または温度を上げるに従い短時間で減少した.(2) 酸素分圧が同じならば,全圧が変化しても酵母の死滅速度は変化しなかった.すなわち,溶存酸素濃度が酵母に致死的影響を及ぼすことがわかった.また,温度の影響も大きく,特に溶液の温度上昇に伴う酸化還元電位の増加は,生存率と高い相関関係(r=0.96)を示した.(3) 加圧の際,攪拌することで,急速に酵母の生存率が低下した.スダチ果汁中に懸濁した酵母(Candidia boidinii SYM-1)は,30°C,5.0MPaで15分間,40°C,10.0MPaでは5分間,さらに加熱の効果も加わる50°Cでは,1分間以内で完全に殺菌できた.(4) スダチ果汁成分への加圧酸素ガスの影響を調べた結果,40°C以下の条件では酵母の殺菌に伴いビタミンC含量も減少した.それに対し,50°CではビタミンCを残存させたまま酵母を殺菌することができた.さらに,香気成分であるD-リモネンや色調に大きな変化は認められず,加熱臭のない新鮮な香味を保持することができた.(5) 酸素ガスで直接果汁を殺菌する方法は,比較的低い圧力(10MPa以下)で処理できることから,高圧殺菌処理(400MPa以上)と比べて装置,コストの面で効率的であり,多量の果汁を連続的に処理できる可能性が示された.

Three types of sidewall, the panel, beam and directly-attached coil type, were adopted as guideway structures for the Yamanashi Maglev Test Line. We evaluated their merits and demerits and developed a new type guideway structure based on the results. Emphasis was placed on improving the efficiency of attaching the sidewalls onto the concrete roadbed as a means to reduce construction costs. We discussed the installation efficiency of several sidewall shapes from all aspects, and eventually adopted an inverted-T-shaped sidewall, fixed to the concrete roadbed by four supports. This paper reports the design of the support in detail, as it is a very important component of the new guideway structure.

In this article, recent advances in the fundamental research in the protein crystallization under high pressure were reviewed. Pressure is expected to be an important parameter to control protein crystallization, since hydrostatic pressure affects the whole system uniformly and can be changed very rapidly. So far, a lot of studies of protein crystallization under high pressure have been done, some less systematic than others. We have particularly focused on fundamental aspects (the solubility and the crystal growth kinetics) of protein crystallization under high pressure. The studies reviewed contribute significantly to high-pressure crystallography and high-pressure protein science.

Solubility of glucose isomerase (from Streptomyces rubiginosus) crystals was measured in situ at 0.1 and 100 MPa. An equilibrium temperature of the crystal with the solution of a given concentration was measured using a two-beam interferometer. The solubility of the crystal decreased to about one-ninth with increasing pressure from 0.1 to 100 MPa at 30 °C. This means that the supersaturation, σ (= ln C/Ce, C = protein concentration, Ce = solubility), increases significantly with increasing pressure at the same temperature. This strongly suggests that the substantial acceleration of the crystallization of glucose isomerase with increasing pressure reported by Visuri et al. is due to the significant decrease in the solubility. The enthalpy and entropy of the dissolution were estimated from the van't Hoff plots. The volume change accompanying the dissolution took a large positive value as ΔV = 54 ± 31 cm3 mol-1 at 30 °C.

Pressure is expected to be an important parameter to control protein crystallization, since hydrostatic pressure affects the whole system uniformly and can be changed very rapidly. So far, a lot of studies on protein crystallization have been done. Solubility of protein depends on pressure. For instance, the solubility of tetragonal lysozyme crystal increased with increasing pressure, while that of orthorhombic crystal decreased. The solubility of subtilisin increased with increasing pressure. Crystal growth rates of protein also depend on pressure. The growth rate of glucose isomerase was significantly enhanced with increasing pressure. The growth rate of tetragonal lysozyme crystal and subtilisin decreased with increasing pressure. To study the effects of pressure on the crystallization more precisely and systematically, hen egg white lysozyme is the most suitable protein at this stage, since a lot of data can be used. We focused on growth kinetics under high pressure, since extensive studies on growth kinetics have already been done at atmospheric pressure, and almost all of them have explained the growth mechanisms well. The growth rates of tetragonal lysozyme decreased with pressure under the same supersaturation. This means that the surface growth kinetics significantly depends on pressure. By analyzing the dependence of supersaturation on growth rate, it was found that the increase in average ledge surface energy of the two-dimensional nuclei with pressure explained the decrease in growth rate. At this stage, it is not clear whether the increase in surface energy with increasing pressure is the main reason or not. Fundamental studies on protein crystallization under high pressure will be useful for high pressure crystallography and high pressure protein science.

2進数における循環小数である10進数の0.1を109回逐次加えるプログラムと104回の部分和をとり、これを105回加え最終的に109回加えるプログラムを作成し、メッセージ通信ライブラリMPIを用いてプログラムの並列化を行った。これらプログラムをAlta Technology AltaCluster、Hitachi SR8000、IBM RS/6000 SP、SGI Origin2000の計4種類の並列計算機を用いて8CPUまでの実行速度および計算精度の評価を行った。その結果、通信量が演算量に比べて小さいため、いずれの並列計算機でもほぼCPU数に応じた高速化が図ることができた。また、計算精度はそれぞれのプログラムとも4つの並列計算機で全く同一であった。逐次加えていく場合は、情報落ちにより正確な解が得られないが、並列化により精度向上が観測された。104回の部分和を加える場合は、逐次計算でも正しい解が得られるが、並列処理によりわずかな精度劣化が見られた。

We investigated ultrastructural changes in the yeast Saccharomyces cerevisiae when exposed to compressed ethylene gas. Transmission electron microscopy (TEM) revealed that intracellular organelles in yeast cells treated with compressed ethylene at up to 0.640 MPa (6.4 atm), especially the nuclear and plasma membranes, were seriously damaged.

Summary: The Bcl-2 family of genes plays important roles in the regulation of apoptosis. The present study was designed to assess the clinicopathologic significance of apoptosis and the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invasive ductal carcinomas (IDCs) of the pancreas. The present study included 66 IDCs that were resected between 1982 and 1998. Apoptosis was assessed by the in situ nick end labeling method and pBcl-2 and pBax were stained immunohistochemically. Apoptosis was quantified as the apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells), and a high AI (>10%) was observed in 26 of the 66 (39%) IDCs. The AI correlated significantly with the extent of nodal involvement. pBax immunoreactivity was detected in 42 of 66 IDCs (64%), and pBax expression was significantly correlated with female gender and showed a significant negative correlation with the extent of nodal involvement. pBcl-2 was expressed in 16 IDCs (24%) but did not show any correlation with the clinicopathologic factors. The AI did not correlate with the expression of pBcl-2 or pBax, but there was a significant correlation between the expression of pBcl-2 and that of pBax; 15 of the 16 pBcl-2(+)IDCs were also pBax(+), and only one pBcl-2(+)IDC was pBax(−). Univariate analysis demonstrated that the degree of apoptosis had no significant influence on the patients' prognosis. pBax or pBcl-2 expression was significantly associated with a better prognosis, and in particular, the pBax(+)pBcl-2(+) group had a significantly higher survival than the other groups. On the other hand, the survival curve of the adjuvant chemotherapy (ACT) group was also higher than that of the surgery alone (SA) group, with borderline statistical signfiicance. The ACT group showed a significantly better survival rate than the SA group for the pBax(+)IDC patients, but the AI and pBcl-2 expression were not correlated with an improved survival rate in the ACT group. Multivariate analysis showed that the AI, pBcl-2 expression, and pBax expression by themselves did not represent significant variables for death owing to IDC, but pBax expression was significantly associated with the efficacy of ACT. In conclusion, pBax expression may be essential for pBcl-2 expression. pBcl-2 and pBax expressions are not significant prognostic factors for patients with IDC, but pBax expression may be beneficial in predicting the effects of ACT on patients with IDC.

Background and Objectives p53 tumor suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair. The Bcl-2 can work to protect cells from apoptosis, which is induced by p53 gene. These facts suggest the significant role of these genes in the genesis and progression of various tumors. The present study was designed to assess the significance of p53 and Bcl-2 protein (pBcl-2) expression on resectable invasive ductal carcinoma (IDC) of the pancreas. Methods The present study included 63 IDCs, which were resected between 1982 and 1998. pBcl-2 and p53 were stained immunohistochemically with monoclonal antibodies. Results pBcl-2 was expressed in 16 (25.4%), and p53 was positively expressed in 32 out of 63 IDCs (50.8%); however, expression of pBcl-2 did not necessarily correlate with that of p53. Although p53 expression did not show any significant influence on the patients' survival, pBcl-2(+) patients showed a higher survival than pBcl-2(−) patients for both p53(+) and p53(−) patients, which suggested that pBcl-2 expression had a more significant effect on the survival of patients than p53 expression. On the other hand, there were no differences in the survival curve between the adjuvant chemotherapy (ACT) group and the surgery alone (SA) group. pBcl-2 expression had no influence on the effect of ACT, the ACT group showed a significantly better survival than the SA group for p53(+) IDC patients. Conclusions pBcl-2 expression is a beneficial prognostic factor for patients with IDC, whereas p53 expression may be beneficial in the prediction of the effects of adjuvant chemotherapy on patients with IDC. J. Surg. Oncol. 2001;76:188–196. © 2001 Wiley-Liss, Inc.

Objective: The biological activities of interleukin-17 (IL-17), a newly cloned cytokine, have not been fully elucidated. The present study was designed to assess the in vitro and in vivo effect of transfecting the IL-17 gene into tumor cells. Methods: A complementary DNA (cDNA) encoding human IL-17 (hIL-17) was obtained by polymerase chain reaction amplification from the human CD4+ T cell cDNA library and inserted into the plasmid pRc/cytomegalovirus to construct an expression vector for the hIL-17 gene. Murine Meth-A fibrosarcoma cells were transfected with the hIL-17 gene using the lipofectin method. The hIL-17 gene-expressing clone (Meth-A/IL-17) was selected and analyzed for cytokine expression by Northern blot. Results: There was no significant difference in the in vitro proliferation rate among parent Meth-A, cells transfected with vector alone and Meth-A/IL-17 cells. When the tumor cells were transplanted subcutaneously into BALB/c nude (nu+/nu+) mice, there was no difference in in vivo growth rates among the three cell lines. Challenge with tumor cells in conventional BALB/c mice, however, resulted in the rejection of Meth-A/IL-17 cells, but the other two lines did grow. After immunization with Meth-A/IL-17 cells, the mice were rechallenged by parent Meth-A or syngeneic MOPC-104E plasmacytoma cells; the immunized mice rejected the Meth-A cells, but not the MOPC-104E cells. Injecting the anti-thy 1,2 (CD90), anti-CD4 or anti-CD8 monoclonal antibody into conventional BALB/c mice resulted in the resumption of in vivo growth of Meth-A/IL-17 cells, but injecting the anti-asialo GM1 antibody did not. Furthermore, flow cytometric analysis demonstrated a significant increase in the expression of major histocompatibility complex (MHC) class I and class II antigens and lymphocyte function-associated antigen-1 on Meth-A/IL-17 cells. Conclusion: Meth-A cells transfected with the hIL-17 gene can induce tumor-specific antitumor immunity by augmenting the expression of MHC class I and II antigens, and both CD4+ and CD8+ T cells may play important roles in inducing antitumor immunity, suggesting the possibility of developing a tumor vaccine incorporating IL-17-transfected tumor cells.

1. To clarify the mechanism of the cardioprotective effect of nicorandil (2-nicotinamidoethyl-nitrate ester), the effects of nicorandil and nitric oxide (NO) donors on the release of ATP, ADP, AMP and adenosine from arterial segments and cultured endothelial cells of the porcine coronary artery were examined. 2. Nicorandil significantly increased the release of total adenyl purines from arterial segments and from cultured endothelial cells. 3. Cromakalim, an ATP-sensitive K+ channel opener, did not affect the release of total adenyl purines from coronary artery segments. 4. s-Nitroso-N-acetyl-D,L-penicillamine and isosorbide dinitrate, NO donors, significantly increased the release of total adenyl purines from coronary artery segments. 5. These results demonstrate that nicorandil stimulates ATP release from the coronary artery by acting not as an ATP-sensitive K+ channel opener, but as a nitrate, thus suggesting the cardioprotective properties of nicorandil.

Neovascularization may be necessary for better and longer function of transplanted islets. Vascular endothelial growth factor (VEGF) is known to be one of the most important factors of angiogenesis. Recently, VEGF was reported to be expressed in islets of normal pancreas. We studied the expression of VEGF and neovascularization related peptides in transplanted islets. To determine the angiogenic microcapillary, immunochemical staining was performed for Factor VIII-related antigen (von Willebrand factor [vWF]) and platelet endothelial cell adhesion molecule-1/CD31 (PECAM-1), both of which are known as markers of the angiogenic microvessel. Transplantable islets were isolated from Lewis rats (8-10 weeks of age) by discontinuous dextran gradient after collagenase digestion. Seven to twelve hundred islets were injected into the portal vein (IPV group, n = 7) or transplanted into subnephrocapsular cavity (SNC, n = 12) of the same descent rats. In the IPV group, the liver was resected 1 hour, 1 week, or 4 weeks after transplantation (Tx). In the SNC group, the kidney was resected 1, 3, 7, or 28 days after Tx. Each tissue was fixed in formaldehyde and embedded in paraffin. Serial 4-microm slices were immunostained for insulin, VEGF, PECAM-1, or vWF using specific antibodies. In IPV group, insulin-positive cells were VEGF positive as were in the normal pancreas at all time points. Islets of 1 hour after Tx were barely PECAM-1 positive as were in normal pancreas, but islets became weakly stained at 7 and 28 days after Tx. In vWF staining, transplanted islets showed stronger staining than those in the normal pancreas. In SNC group, VEGF was also stained in insulin-positive cells at 1, 3, 7, and 28 days. In PECAM-1 staining, islets of 1 day after Tx were barely stained as were in normal pancreas. However, the staining was increasingly enhanced from 3 to 7 days and then appeared weakened at 28 days after Tx. In vWF staining, islets were always vWF positive, as was seen in IPV group. This study revealed that PECAM-1 appeared in islets after islet Tx, suggesting that neovascularization occurs within the islet grafts. On the other hand, VEGF of transplanted islet did not obviously vary with time. Enhancement of the neovascularization may lead to better results of islet Tx.

Recent advances in molecular biological techniques have made the search for the factors in pancreas regeneration more intensive. Many transcription factors and growth factors have been suggested to be involved in the proliferation, differentiation, and maintenance of endocrine and exocrine pancreas. Among the transcription factors, PDX-1 has been examined in a major pancreatectomy model and is suggested to play a role in beta-cell differentiation. Among the growth factors and related peptides, reg protein seems to be a promising candidate which can be applied to clinical practice. Our previous study showed that proton pump inhibitor-induced endogenous hypergastrinemia enhanced insulin secretion and pancreas regeneration. Our results and other studies have suggested that endogenous gastrin induces beta-cell differentiation. On the other hand, the role of classical gut hormones such as gastrin and cholecystokinin in pancreas regeneration has become less significant, as it has been shown that rodents deficient in the genes for these hormones form almost normal pancreas. Results in dogs have shown that pancreas regeneration occurs after major pancreatectomy. A preliminary experiment in primates also suggests latent developmental capacity in the adult primate pancreas. These results lead us to expect that regeneration of the remnant pancreas after subtotal pancreatectomy would be a good target of certain therapies to enhance pancreatic regeneration.

今回,われわれは後腹膜原発悪性Triton腫瘍の1例を経験した.症例は58歳,男性.主訴は食後腹満感,腹部腫瘤.画像にて後腹膜腫瘤,多発性肝腫瘤を認めるも確定診断がつかないため,開腹下生検を施行した.病理学的検査ではHE染色で棚状に増殖する腫瘍細胞が認められ,免疫染色でS-100蛋白,NSE,NFが陽性で,一部にmyoglobin, desminに陽性である横紋筋芽細胞が散在していたため,悪性Triton腫瘍と診断された.術後,化学療法は効果なく3カ月目に肝不全にて死亡した.悪性Triton腫瘍は予後不良で,極めて稀な疾患とされている.本腫瘍に対しては,早期発見と確実な切除,さらには化学療法や放射線治療を加えた集学的治療が重要と考えられた.

症例は, 48歳,女性.下腹部痛,嘔気,嘔吐を主訴に来院.顔貌は苦悶状,蒼白で,腹部は著明に膨隆・緊満しており,腹部全体に圧痛を認めた.腹部単純X線検査にて下腹部を中心に類円形の蜂巣状透亮像を多数認め,左右横隔膜下にfree airを多量に認めたため,腸管嚢腫様気腫症が疑われたが,多量のfree airを呈した腸管嚢腫様気腫症の症例報告は少なく,腹部全体に圧痛を認めたことより,緊急手術を施行した.開腹するとfree airを多量に認め,グダラス窩に漿液性腹水を認めた.空腸からS状結腸まで腸管は著明に拡張し,腸管壁,腸間膜に嚢腫様気腫性変化を認めた.空腸の一部は気腫性変化が強く,腸管壁の浮腫と肥厚が著明であり,同部位の空腸を切除し,腸管内圧の減圧目的にてイレウスチューブを挿入した.手術翌日の腹部単純X線検査ですでに蜂巣状透亮像は消失しており,術後22日目に軽快退院した.

3年間,平滑筋腫として経過観察されていた直腸原発gastrointestinal stromal tumor (GIST)の1例を経験したので報告する.症例は71歳,男性.主訴は肛門周囲違和感,下腹部痛. 3年前,近医にて直腸平滑筋腫と診断され,経過観察されていたが,肛門周囲違和感,下腹部痛を生じて来たため当院受診.精査にて悪性が否定できず,腹会陰式直腸切断術を施行した.腫瘍は境界明瞭で,周囲組織への浸潤は認めなかった.切除標本の免疫組織学的検索にて, GIST uncommitted typeと診断された. 1年経過した現在も再発の徴候は認めていない. GISTは最近の新しいカテゴリーであり,悪性度の定義も未だ定説はなく,免疫組織学的分類の臨床的意義について文献的考察を加え報告する.

Summary p53 tumor-suppressor gene has a dual role as a trigger of apoptosis and as an initiator of DNA repair. The cyclin-dependent kinase inhibitor WAF/1-p21 is induced by wild-type p53 and has been implicated as a downstream mediator of the growth-suppressing and apoptosis-promoting function of wild-type p53, suggesting an impact on the effectiveness of chemotherapy. This study was designed to assess the significance of p53 and WAF/I-p21 expression in the prognosis of patients and the efficacy of adjuvant chemotherapy for resectable invasive ductal carcinoma (IDC) of the pancreas. A total of 58 patients with primary IDC of the pancreas underwent pancreatectomy between 1982 and 1996: 28 patients underwent surgery alone, and 30 patients received postsurgical adjuvant Chemotherapy p53 and WAF/I-p21 were stained immunohistochemically with anti-p53 monoclonal antibody (mAb) and anti-WAF/I-p21 mAb. p53 was positively expressedin 29 (50%) of 58 primary lesions, and p21 was expressed in 24 (41%) lesions; however, p21 expression did not necessarily correlate with p53 expression. The survival curve of the patients with p53(+) IDC was significantly lower than that of those with p53(-) IDC, and p21(+) patients showed a higher survival curve than did p2 1 (-) patients, but this difference was not statistically significant. When p53 and p21 expression were analyzed in combination, the patients with p53(+)p21(-) IDC were found to have a significantly poorer prognosis than others. On the other hand, the survival curve of the adjuvant chemotherapy group was also higher than that of the surgery-alone group, but this difference was not significant. In a multivariate analysis, p21 expression was a significantly low risk factor for death due to IDC overall, and adjuvant chemotherapy was found to decrease the risk of death from IDC in p53(+) patients. Evaluation of expression of p53 and WAF/l-p21 may be beneficialin the prediction of the patient's prognosis as well as prediction of the effects of adjuvant chemotherapy in pancreatic cancer patients.

Trehalose (α-D-Glucopyranosyl α-D-glucopyranoside) is one of the disaccharides and exists widely in animals, plants and bacteria. In this article, the role of trehalose in microbial cells was discussed from the point of view of their stress response: synthesis of heat shock proteins and trehalose, and the induction of stress tolerance. Further-more, an outline of the behavior of microbes under high pressure was also given. The concrete contents of the article are (1) effects of trehalose on thermotolerance of pressure-shocked yeast, (2) effects of temperature and pressure on the death rate of Lactobacillus casei and Escherichia coil, (3) properties and functions of trehalose, (4) extreme barotolerance of tardigrade, and (5) correlation of thermotolerance and barotolerance of yeast and the mean number of equatorial OH groups in sugar molecules.

We performed ab initio MO-MD simulation based on the fragment MO (FMO) method using the (−)-epicatechin gallate in order to examine the efficiency of fragmentation pattern in comparison with conventional MO-MD. We clearly demonstrated that the FMO-MD simulation gave sufficient results concerning the trajectory of the total energy and the geometry difference.

FMO-MO (Molecular orbitals (MOs) of the fragment MO (FMO) method) for (−)-epicatechin gallate were calculated to examine the dependency of the accuracy on the fragmentation patterns and on the basis set, and the results were compared to those obtained using conventional MO calculations. Results also show that the FMO-MO can be used as the initial guess in self-consistent field calculations.

Difference in the potential energy surfaces (ΔE) obtained from the fragment MO (FMO) method and conventional ab initio Hartree–Fock SCF-MO (HFMO) method was investigated using the best fragmentation pattern of (−)-epicatechin gallate. In the lower energy region (

The fragmentation pattern dependence of the total energy and atomic charge difference between the fragment MO method and conventional ab initio Hartree–Fock SCF-MO method (HFMO) was investigated us...

The clinical course of our patient suggests the association between chronic pancreatitis and primary sclerosing cholangitis (PSC), as well as the usefulness of prednisolone for the treatment of this condition.Although alterations in the pancreatic duct have been reported, the association between chronic pancreatitis and PSC remains uncertain.A long-term follow-up case of chronic pancreatitis accompanied by PSC is presented. A 58-yr-old man complaining of epigastric distress was admitted to our hospital in July 1990. Endoscopic retrograde cholangio-pancreatography (ERCP) showed a stricture of the distal common bile duct and a narrowing of the main pancreatic duct (MPD) with mild ectasia of its branches in the head of the pancreas. ERCP taken in June 1992 revealed localized narrowings in both the right and the left main hepatic ducts, and irregularity of the MPD through the entire pancreas. An ERCP taken in June 1996 showed a progression of the narrowings of the bile ducts. The patient was diagnosed as having chronic pancreatitis accompanied by PSC. ERCP revealed a remarkable improvement of the bile ducts after 4 wk of treatment with prednisolone.