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Nano-prober has the increasing importance for advanced semiconductor device process. Conventional SEM type Nano-prober face the problems, device degradation with electron bombardment and resolution limit. The AFM Nano-prober can work in air, so it is so easy to use for its operation. We report the new type AFM Nano-prober that applied the self-sensing type AFM. This method has the simple structure and easy to use. In the case of Nano-prober that constructed with multiple AFM, this simple method is best choice in this purpose.

We have developed a system to measure absolute distance. By stabilizing the output direction of dye laser, improving the accuracy of the wavelength and reducing the non-linear errors caused by stray beams, an accuracy of +or-1.3 nm and a resolution of 0.2 nm were obtained for a range of 100 mm. In our system, as wavelengths could be set free, a systematic procedure, i.e., setting synthetic wavelengths in a geometric ratio to minimize the number of output wavelengths within a range to be measured, became possible and greatly extended the range. Our proposal seems to be an original one.

With a tunable CW dye laser oscillating in a single longitudinal mode, measurement of an absolute distance is demonstrated with the method of excess fractions. Five beams which have different wavelengths are emitted sequentially from the dye laser, and the interferometric phase is measured for each wavelength. An interferometric order number for a wavelength can be calculated from values of wavelengths and phases. Then a precise value of length is obtained. This method is similar to measuring distances by using group delay as used in VLBI and microwave ranging. The measured accuracy was within +or-8.8 nm between 0 and 10 mm (at an absolute distance of 0.1-10.1 mm). >

We develop novel layer-3 (L3) Internet protocol (IP) packet switches to connect 80 Gbps WDM-based optical packet switching (OPS) networks with 10 Gbps Ethernet (10GbE). A L3 switch, which is the ingress edge node of the OPS network, generates an optical label according to a look-up table and the destination address of an IP packet, and then encapsulates the almost 10 Gbps IP packet into an 80 Gbps (8-wavelength x 10 Gbps) optical packet Another type of L3 switch, which is the egress edge node of the OPS network, decapsulates the IP packet from the optical packet and generates a lOGbE frame accommodating the IP packet according to a look-up table. We achieve the transmission of 7.2-Gbps IP packets throughput with a packet loss rate under 10-6 and demonstrate smooth UDP/IP-based 3D high-definition television (HDTV) video-streaming via the L3 switches and 80 Gbps WDM-based OPS system.

40-Gb/s optical packet label recognition, switching, and buffering using an optoelectronic logic module and a waveguide matrix optical switch module are demonstrated. The switch can achieve a high ON/OFF extinction ratio of 25-26 dB and a first switching time of less than 2 ns.

At Wakasa-wan Energy Research Center, Fukui, Japan, the accelerator system is now under construction. The system consists of a 200 keV ion implanter, a 5 MV Schenckel type tandem accelerator and a 200 MeV proton synchrotron. The ion implanter is for the improvement of the surface of the material. By using the tandem accelerator, we can perform the element analysis, the improvement of the bio-species and ion-implantation into various materials. The tandem accelerator works as an injector for the synchrotron and the synchrotron is for the cancer therapy and also bio and material science.

We developed novel network interfaces, for example 10 Gbit Ethernet to 80 Gbit/s optical-packet (10 GbitE-80 GbitOP) or 80 Gbit/s optical-packet to 10 Gbit Ethernet (80 GbitOP-10 GbitE) converters (collectively called as 10 GbitE/80 GbitOP converters), to connect optical packet switching (OPS) networks with IP technology-based networks. By using newly developed arrayed burst-mode optical packet transmitters/receivers together, the 10 GbitE-80 GbitOP converter at the ingress edge node of the OPS network encapsulates an IP packet into an 80(8lambdat10)nGbit/s dense wavelength division multiplexing (DWDM)-based optical packets and generates an optical label based on a lookup table and the destination addresses of the IP packet. The 80 GbitOP-10 GbitE converter at the egress edge node decapsulates the IP packet from the optical packet and generates a 10 GbitE frame accommodating the IP packet according to a lookup table. By using these network interface devices and OPS system based on multiple optical label processing, we achieved, for the first time, 74-km single-mode fiber transmission, switching, and buffering of 80(8lambdat10)nGbit/s DWDM-based optical packets encapsulating almost 10 Gbit/s IP packets with error-free operation (IP packet loss rate < 10-6).

1. To delineate the mechanism by which cyclic AMP (cAMP) suppresses interleukin (IL)-5 synthesis, the effects of prostaglandin (PG) E2, forskolin, dibutyryl (db)-cAMP and the Ca2+ ionophore, ionomycin on cytokine synthesis, proliferation and CD25 expression of human T cells were investigated. Further studies were performed by measurement of the intracellular concentrations of cyclic AMP ([cAMP]i) and Ca2+ ([Ca2+]i) and by electrophoretic mobility shift analysis (EMSA). 2. PGE2, forskolin and db-cAMP suppressed IL-5 production by human T cell line following T cell receptor (TCR)-stimulation. PGE2 suppressed TCR-induced messenger RNA (mRNA) expression of IL-2, IL-4 and IL-5, as well as proliferation and CD25 expression. 3. Cyclic AMP-mediated suppression of cytokine synthesis, proliferation and CD25 expression in human T cells were attenuated by ionomycin. 4. [cAMP]i was increased by PGE2 and forskolin. PGE2 suppressed the TCR-induced biphasic increase in [Ca2+]i. EMSA revealed that four specific protein-DNA binding complexes related to NF-AT were detected at the IL-5 promoter sequence located from -119 to -90 relative to the transcription initiation site. The slowest migrating complex induced by TCR stimulation was enhanced by PGE2 and further upregulated by ionomycin. Another binding which did not compete with cold AP-1 oligonucleotides, was constitutively present and was unaffected by PGE2 but enhanced by ionomycin. 5. The suppressive effect of cyclic AMP on human IL-5 synthesis is mediated by interference with intracellular Ca2+ mobilization but distinct from the NF-AT-related pathway.

To evaluate the efficacy of polaprezinc, a mucosal protective agent, in combination with a 7-day triple therapy containing lansoprazole, amoxycillin and clarithromycin, as a treatment for Helicobacter pylori.Sixty-six consecutive patients suffering from dyspeptic symptoms with H. pylori infection were randomly allocated to one of two regimens: one group (LAC; n = 31) received lansoprazole 30 mg b.d., amoxycillin 500 mg b.d. and clarithromycin 400 mg b.d. for 7 days. The other group (LACP; n = 35) received the LAC regimen plus polaprezinc 150 mg b.d. for 7 days. H. pylori status was evaluated by rapid urease test, histology and culture at entry and 4 weeks after treatment.Five patients did not complete the treatment: no follow-up endoscopy was performed on two patients in the LAC group; one patient in the LAC group and two in the LACP group had their treatment stopped due to severe diarrhoea. By per protocol analysis, H. pylori eradication was achieved in 24 of the 28 evaluable patients (86%; 95% CI: 72-100%) after LAC therapy, and in 33 of the 33 evaluable patients (100%) after LACP therapy (P0.05). On intention-to-treat analysis, the rates of eradication were 24 of 31 patients (77%; 95% CI: 62-93%) in the LAC group, and 33 of 35 patients (94%; 95% CI: 86-100%) in the LACP group (P0.05).A 7-day triple therapy with lansoprazole, amoxycillin and clarithromycin is effective in H. pylori eradication, but this regimen is significantly improved by the addition of polaprezinc.

Objective: The aim of this study was to compare Sephadex G-200 (Sephadex)-induced airway hyperresponsiveness (AHR) and pulmonary eosinophilia among some rat strains.¶Materials: Sprague-Dawley (SD), Brown-Norway (BN), Fischer 344 (Fischer), Lewis and Wistar-Kyoto (WKY) rats were used.¶Methods: Sephadex (0.5 mg/animal) was intravenously administered on days 0, 2 and 5. Measurement of AHR using serotonin and bronchoalveolar lavage (BAL) was performed on day 7.¶Results: The Lewis strain exhibited significant AHR to Sephadex but the BN, Fischer and WKY strains did not. Additionally, the degree of AHR in Lewis rats was smaller than in SD rats throughout the study. Eosinophils in BAL fluid, however, increased in each strain, and the magnitude of the response was BN > Lewis > WKY > Fischer. Both the AHR and pulmonary eosinophilia in Lewis rats were inhibited by dexamethasone (0.1 mg/kg, p.o. × 3).¶Conclusion: These results indicate that the Lewis rat is a useful strain for analysis of the mechanism of Sephadex-induced AHR and airway inflammation.

The effect of T-440, a selective type IV phosphodiesterase inhibitor, on cytokine production by peripheral blood mononuclear cells (PBMC) of atopic asthmatics was investigated. T-440 suppressed allergen-induced interleukin (IL)-5 production with a high potency (IC50 = 0.039 microgram/ml) and allergen-induced proliferation of PBMC (IC50 = 0.30 microgram/ml). T-440 also suppressed IL-2, IL-4 and IL-5 production by concanavalin A-activated PBMC in concentration-dependent manner. The IC50 values for the suppression of cytokine synthesis were 0.11 microgram/ml for IL-2, 0.57 microgram/ml for IL-5 and 7.7 micrograms/ml for IL-4. cAMP-elevating agents, such as PGE2, forskolin and dibutyryl cAMP, suppressed IL-2, IL-4 and IL-5 production by concanavalin A-stimulated PBMC in a manner similar to that of T-440. T-440 inhibited cAMP-phosphodiesterase activity and raised the intracellular cAMP level of PBMC in a concentration-dependent manner, suggesting that the increase of intracellular cAMP caused by T-440 results in the reduction of cytokine production. We conclude that T-440 suppressed cytokine production by peripheral T lymphocytes via the protein kinase A pathway and may be an effective modality to treat atopic diseases associated with eosinophilic inflammation.

We have isolated two polypeptides from cementum one of which promotes the growth and the other the attachment of periodontal cells. One polypeptide, the cementum derived growth factor (CGF), was extracted from healthy human and bovine teeth by 1 M CH3COOH and purified by heparin-affinity chromatography and HPLC. The CGF is a 23 kDa polypeptide which is mitogenic to fibroblasts and smooth muscle cells. It is active alone, but its activity is highly potentiated by plasma-derived serum or EGF. It induces classical mitogenic signaling events, which include Ca++ mobilization, inositol phosphate hydrolysis, activation of phosphokinase C (PKC) and transcription of cellular protooncogenes c-fos and jun-B. The magnitude and pattern of activation of signaling events and their susceptibility to PKC inhibitors and pertussis toxin indicated that the CGF may be a distinct molecular species. The CAP is a 55 kDa polypeptide which promotes the attachment and spreading of fibroblasts, smooth muscle cells, bone cells and endothelial cells, but not epithelial cells. Antibodies to CAP immunostain cementum, but not other tissues. Root surfaces bind CAP. The CGF and CAP do not appear to be present in adjacent periodontal structures. Our data show that the CAP and CGF selectively interact with periodontal cell populations and affect their biological activities, and thus may influence the formation and regeneration of periodontal connective tissues.

Background We previously found that GADD45b, which is associated with cellular stress response and apoptosis regulation, contributes to sorafenib resistance in HCC cells. The present study explored the role of GADD45γ, another GADD45 family protein, in HCC treatment. Methods HCC cell lines tested included Huh-7, HepG2, Hep3B, Huh-7R, HepG2R, the latter two sorafenib-resistant cell lines established by continuously exposure of Huh-7 and HepG2 cells to sorafenib. GADD45γ expression was examined by quantitative real-time PCR (qRT-PCR) and western blotting. Control of GADD45γ transcription was examined by luciferase reporter assay using a series of reporter plasmids with deletions or site-directed mutants of the 5′-flanking region of GADD45γ promoter. Apoptosis was analyzed by flow cytometry and western blotting. Expression of GADD45γ in human HCC tumor tissues was measured by qRT-PCR and immunohistochemistry. Results GADD45γ mRNA and protein levels were increased after sorafenib independent of cellular MEK/ERK activity. GADD45γ induction was more prominent in sorafenib-sensitive HCC cells (Huh-7 and HepG2, IC50 6-7 µM) than in sorafenib-resistant HCC cells (Hep3B, Huh-7R and HepG2R, IC50 12-15 µM). Knockdown of GADD45γ expression partially abrogated the pro-apoptotic effects of sorafenib in sorafenib-sensitive cells but not sorafenib-resistant cells. The region -449/ - 82 in the 5′-flanking region of GADD45γ promoter was found crucial for GADD45 gamma induction by sorafenib. Decreased GADD45γ expression in HCC tumor tissue was associated with worse overall survival in patients who underwent surgery for HCC. Conclusions Induction of GADD45γ expression contributes to sorafenib-induced apoptosis in HCC cells. The role of GADD45γ as a predictive biomarker for sorafenib sensitivity in HCC warrants further exploration. (Supported by grants NSC-100-2325-B-002 -042, NSC 100-2314-B-002 -058-MY3, DOH100-TD-B-111-001, and NHRI-EX101-9911BC.)

We report a rare case of prostatic abscess with Crohn's disease in a 21-year-old male. Computed tomography showed a typical prostatic abscess. Moreover, filling of the abscess cavities with contrast medium was demonstrated after micturition, which represented the rupturing of the abscess into the urethra. Crohn's disease should be included in the differential diagnosis of prostatic abscesses even in young males.

1-(3，4，5-trimethoxybenzyl)-5，7-dihydroxy-1，2，3，4-tetrahydroisoquinoline HCl（DTI）の光学異性体について，イヌで気管支拡張作用を検討した結果，静脈内投与で(-)体（l-DTI）は（±）体（DTI）の約2.5倍の活性を示したが，（+）体（d-DTI）はDTIの1/10以下の活性しか示さなかった．そこで，l-DTIを用い，イヌの気管支拡張作用ならびに心臓血管系に対する作用をisoproterenol（Iso）と比較検討した．静脈内投与によるlDTIの気管支拡張作用はIsoの約1/2.6であったが，作用持続はIsoより長かった．一方，l-DTI（0.1μg/kg，i.v.）による麻酔犬の心収縮力，心拍数，Lvdp/dtおよび心仕事量の増加作用はIsoの1/5～1/7で，気管支に対する作用より弱かった．しかし，降圧作用はIsoの約1/3，動脈内投与による大腿動脈血流量増加作用はIsoの1/2.3で，気管支に対する作用とほぼ同程度の活性を示した．これらの気管支ならびに心臓血管系に対するl-DTIの作用はpropranololによって抑制された．以上の結果は，(±)体であるDTIの気管支拡張作用の大部分は(-)体であるl-DTIによること，およびl-DTIはadrenergic β-stimulantに属するけれども心臓作用より気管支拡張および血管拡張作用が強いことを示唆している．

Bronchodilating action of l-MTI was investigated by intravenous administration to anesthetized animals and the results were compared to those seen with isoproterenol. Bronchoconstriction was induced by histamine or serotonin. Under pentobarbital anesthesia, the bronchodilating activity of l-MTI was approx. 1/20 that of isoproterenol in cats and dogs, but less than 1/100 that of isoproterenol in monkeys and guinea pigs. The results indicate that the bronchodilating activity of l-MTI is variable and species dependent. It was demonstrated, however, that in guinea pigs, l-MTI did not produce any bronchodilating activity, when the animals were anesthetized with urethane. The absence of the bronchodilating response in animals under this anesthesia was also seen in vagotomized, adrenalectomized and reserpinized, norepinephrine-infused guinea pigs. On the contrary, l-MTI exhibited the bronchodilating action in reserpinized, pithed or hexamethonium-treated guinea pigs anesthetized with urethane. On th other hand, isoproterenol produced a bronchodilating action in all preparations mentioned above. It was also evident that l-MTI suppressed the bronchodilating action of isoproterenol in pentobarbital anesthetized guinea pigs. In addition, l-MTI increased the heart rate of guinea pigs with a low beating rate, but decreased it when the control rate was high. These results suggest that at least in guinea pigs, l-MTI acts as a partial agonist and that the effect of l-MTI on the bronchial system depends on the sympathetic tone and/or sympathetic bronchodilator reflex, as proposed by McCULLOCH ET AL. (9).

Chromogenic peptide substrates S-2222 designed for F. Xa assay is also amidolyzed relatively slowly by thrombin; in the usual F. Xa assay system however a considerable amount of thrombin is inevitably formed. In the present study, therefore, No. 805, highly selective synthetic thrombin inhibitor, (4 methyl- (methyl-tetrahydro-quino- linesulfonyl-arginyl ][ 2-piperidinecarboxylic acid), having extremely potent stereostructure (2R, 4R) at 4-methyl-2- piperidinecarboxylic acid portion, which was reported by S. Okamoto et al. in 1980, was used to improve selectivity of S-2222 for F. Xa assay. F. Xa in human plasma activated by either Russel’s viper venom or thromboplastin was estimated according to the methods by Aurell et al. . Ki of No. 805 for thrombin was found 0.019 juM and presence of No. 805 of 5 mM inhibited thrombin at least by 99.5%. However, No. 805 of this concentration showed no inhibition for purified F. Xa. Results obtained from chromogenic assay for F. Xa by S-2222 with or without No. 805 of 5 mM indicated that 10̴20% of amidolysis was derived from the action of thrombin formed in the assay system. Concerning high Km value of S-2222 to thrombin, molecular concentration of thrombin formed in the assay system was calculated as 3̴6 times of the F. Xa molecular concentration. Use of highly selective and potent synthetic thrombin inhibitor seems to be promissing to improve the selectivity of some other chromogenic assay also.

Among a novel series of synthetic thrombin-inhibitors belonging to arginine derivatives found by S. Okamoto et al. , No. 205, dansyl-arginine-piperidineamide, was reported by Mann and his associates to show the enhancement of fluorescence intensity when bound to thrombin. However, No. 205 was reported by S. Okamoto et al. to inhibit pseudocholinesterase with very low Ki also, while No. 805, (4R- methyl- [ methyl-tetrahydro-quinolinesulfonyl-arginyl- ] 2R- piperidinecarboxylic acid), showed practically no inhibitory action on pseudocholinesterase remaining very potent inhibitory action to thrombin with a Ki of 0.019 μM. Therefore, comparative studies of fluorescence variation with No. 205 and No. 805 were made using thrombin, pseudocholinesterase and truecholinesterase as the target enzymes and the following results were obtained. 1) The enhancement of fluorescence intensity of No. 205 with thrombin was corn- firmed but the same order enhancement of fluorescence intensity of No. 205 was also observed with pseudocholinesterase, but not with truecholinesterase (to this enzyme Ki of No. 205 was large), indicating that the enhancement is concomitant with the inhibitory binding of No. 205 with the enzymes. 2) The enhancement of fluorescence intensity of No. 205 with thrombin was clearly reversed by the addition of No. 805, indicating the replacement of No. 205 bound to the thrombin by No. 805. This supports the possibility of the fluorometric differentiation of thrombin from pseudocholinesterase, which allows us to discuss the histo- chemical application of synthetic thrombin inhibitors to demonstrate the local thrombin.

The vasodilator action of CV-705 was investigated in a number of vascular regions of anesthetized mongrel dogs and this action was compared with that of papaverine. When CV-705 was administered intravenously the vertebral, common carotid and internal carotid blood flow was increased considerably and was long-lasting. These effects were most remarkable among the regions tested. Femoral, aortic and coronary blood flow were also increased. On the other hand, the blood flow through superior mesenteric artery and portal vein increased only slightly. Renal blood flow was decreased slightly after an intravenous administration, whereas an increase was observed after an intra-arterial administration. Such a regional distribution of blood flow after CV-705 was quite similar to that observed with papaverine. CV-705 was well absorbed through the digestive tract. CV-705 given intravenously showed a weak hypotensive and positive chronotropic action. The increase in common carotid blood flow induced by intra-arterial administration of CV-705 was not affected by pre-treatment with atropine or triprolidine, but was partially suppressed by pre-treatment with propranolol. These results suggest that CV-705 has a papaverine-like action as well as a weak beta-adrenoceptor stimulating action, consequently a vasodilator action occurs.

Effects of diltiazem, a calcium antagonist, on the cardiovascular system in the pentobarbital anesthetized dogs were investigated. Diltiazem (100 micrograms/kg and 300 micrograms/kg, i.v.) decreased blood pressure, heart rate and total peripheral resistance, while cardiac output and stroke volume were markedly increased. The max dp/dt of left ventricular pressure tended to increase with a dose of 100 micrograms/kg. Left ventricular end-diastolic pressure was slightly increased with a dose of 400 micrograms/kg. Rate pressure product was significantly reduced. Diltiazem (30 micrograms/kg and 100 micrograms/kg) increased pulmonary arterial flow together with the increase in both systolic and diastolic pulmonary arterial pressure. Diltiazem (100 micrograms/kg) increased common carotid, femoral and superior mesenteric arterial blood flow by 30 to 40%, whereas vertebral blood flow was increased by over 100%. The dose dependency in the vertebral blood flow was remarkable. Response of the vertebral artery to diltiazem was similar to that reported in the case of the coronary artery. In the His bundle electrogram, diltiazem increased the AH interval by about 10% at 100 micrograms/kg and 25% at 200 micrograms/kg, without changing the HV interval. Diltiazem-induced AH prolongation was completely depressed by epinephrine but only partially so by CaCl2. Thus, the effects of diltiazem on sinus rhythm and AV conduction in the anesthetized dog were more potent than the effects on cardiac contractility, although weaker than the effects of the vasodilating action. The vasodilator effects appear to be the primary action of diltiazem on the cardiovascular system.

A noticeable effect of dansyl-arginine-methyl-piperidine amide in animal experiments is described, which is one of the representative compounds of a new series of potent thrombin-inhibitors synthetized by the authors very recently. The inhibitor solution was intravenously administered to rabbits by means of the infusion pump to maintain the inhibitor in the circulatory blood at a concentration intended. When bovine thrombin was intravenously administered (5 NIH units/Kg/min) for 75 minutes, a remarkable decrease of plasma fibrinogen content was observed in control, while any decrease of fibrinogen content was hardly observed at the inhibitor concentration of 10 ~ 20 μMin plasma. Further, the decrease of plateletes in number due to thrombin infusion (7.5 ~ 9NIH units/Kg/min) for 5 minutes was suppressed satisfactorily at the inhibitor concentration of 1 ~ 2 μM in plasma.These results indicate that the new synthetic thrombin-inhibitor is effective enough at a very low concentration to control the hazard due to thrombin given in vivo, encouraging the authors to extend the studies further toward the application.

Bronchodilator effects of diltiazem were investigated in the isolated guinea pig tracheal chain and in the anesthetized cat. Interaction of diltiazem with isoproterenol (iso) was also examined. Diltiazem (10(-4) g/ml) relaxed by 70% the tracheal chain contracted by histamine, 10(-5) g/ml. This effect of diltiazem was not affected by pretreatment with propranolol, 3 X 10(8) g/ml. Diltiazem (400 microgram/kg, i.v.) diminished by 20% the elevation of intratracheal pressure induced by serotonin aerosol, the effect of which lasted for approximately 20 min. On the other hand, diltiazem (10(-5) g/ml) produced no influence on the iso-induced relaxation of the guinea pig trachea. In the anesthetized dog, diltiazem (20 microgram/kg/min, i.v.) did not affect the iso-induced bronchodilation when histamine was used as a spasmogen, while the positive chronotropic action of iso was diminished. On the contrary, propranolol (30 microgram/kg, i.v.) potentiated the bronchoconstrictor effect of histamine and suppressed both the bronchodilating and positive chronotropic actions of iso. Thus, the effects of diltiazem differed from those of propranolol. In summary, diltiazem showed bronchodilation both in vitro and in vivo, although the activity was not so potent, With regard to the iso-induced bronchodilation, diltiazem had no effect at a dose which diminished the positive chronotropic action of iso.