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Background: Taselisib (GDC-0032) is an orally bioavailable, potent and selective phosphoinositide 3-kinase (PI3K) inhibitor. Preclinical data showed that taselisib had increased antitumor activity against PIK3CA (gene encoding the PI3Kα isoform) mutant tumors. This study aimed to investigate the safety, tolerability and pharmacokinetics (PK) of taselisib as monotherapy and in combination with fulvestrant in Japanese patients (pts). Materials and methods: A 3+3 design was used. In Phase Ia, pts with advanced solid tumors received taselisib tablet monotherapy (2, 4 or 6 mg once daily [QD]), and safety and PK were evaluated. In Phase Ib, pts with hormone receptor-positive locally advanced or metastatic breast cancer received taselisib (2 or 4 mg QD) in combination with fulvestrant (500 mg at a time), and safety and PK were evaluated. Maximal administered doses of 6 mg QD as a single agent and 4 mg QD in combination with fulvestrant were based upon prior clinical trial experience with taselisib (Juric D. et al. AACR 2013, Abstract LB-64; Juric D. et al. SABCS 2013, Abstract PD1-3). Results: As of 15 Mar 2015, 9 pts (PIK3CA mutant: 2 pts) were enrolled in Phase Ia and 3 pts in Phase Ib. Phase Ia dose-escalation study has been completed and Phase Ib is ongoing. In Phase Ia, no dose-limiting toxicity (DLT) was observed at any dose level tested (maximum administered dose of 6 mg QD). Common (≥3 pts) adverse reactions (ARs) were stomatitis (4 pts), rash (3 pts) and diarrhea (3 pts); the only Grade ≥3 AR was neutropenia (1 pt). Partial response was observed in 1 pt who received taselisib 4 mg and had a PIK3CA mutant breast tumor. Stable disease was observed in 4 pts. Cmax and AUC indicated a dose-proportional PK profile of taselisib within the dose range tested. Moreover, taselisib PK in Japanese pts was consistent with the PK reported from North American and European pts (Juric D. et al. AACR 2013, Abstract LB-64). In Phase Ib, 3 pts received taselisib 2 mg in combination with fulvestrant and no DLT was observed. Preliminary ARs were similar to those with monotherapy and no Grade ≥3 AR was reported. Confirmation of tolerability of taselisib 4 mg in combination with fulvestrant is under evaluation. Conclusion: Taselisib monotherapy was well tolerated in Japanese pts up to a dose of 6 mg, which is the recommended dose in non-Japanese pts. Promising preliminary activity of monotherapy was observed in advanced solid tumors, especially in a pt with PIK3CA mutant tumor. The combination of taselisib 2 mg with fulvestrant is well tolerated. Investigation of tolerability of taselisib 4 mg in combination with fulvestrant is ongoing. Final results of this study will be presented here at the Symposium this year. Citation Format: Kobayashi T, Nakano K, Tomomatsu J, Nara E, Ito Y, Kobayashi K, Fukada I, Araki K, Shimomura A, Shimoi T, Kodaira M, Yunokawa M, Yonemori K, Shimizu C, Nakamura K, Kotani N, Inatani M, Tamura K, Takahashi S. Phase Ia/Ib study of taselisib (GDC-0032), a potent and selective phosphoinositide 3-kinase inhibitor, in Japanese patients with advanced solid tumors or hormone receptor-positive locally advanced or metastatic breast cancer (JO29196 study). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-14-10.

We propose a new 2-port SRAM with a single read bit line (SRBL) eight transistors (8 T) memory cell for a 45 nm system-on-a-chip (SoC). Access time tends to be slower as a fabrication is scaled down because of threshold voltage (Vt) random variations. A divided read bit line scheme with shared local amplifier (DBSA) realizes fast access time without increasing area penalty. We also show an additional important issue of a simultaneous read and write (R/W) access at the same row by using DBSA with the SRBL-8T cell. A rise of the storage node causes misreading. A read end detecting replica circuit (RER) and a local read bit line dummy capacitance (LDC) are introduced to solve this issue. A 128 bit lines - 512 word lines 64 kb 2-port SRAM macro using these schemes was fabricated by a 45 nm bulk CMOS low-standby-power (LSTP) CMOS process technology [1]. The memory cell size is 0.597 mum2. This 2-port SRAM macro achieves 7 times faster access time without misreading.

We propose a compact model for a Flash memory cell that is suitable for circuit simulation. The model includes a hot-electron gate current model that considers not only channel hot electron injection but also channel initiated secondary electron injection to express properly substrate bias dependence of gate current. Tunneling gate current for erasing is expressed by the BSIM4 tunneling gate current model. Good agreement between measured and simulated results of both programming and erasing characteristics for 130-nm technology Flash memory cells indicates that our model is useful in designing and optimizing circuit for Flash memories.

Sliding friction and wear tests were performed for four sintered ceramics including mullite, alumina, silicon carbide and titanium diboride (TiB2), in various combinations at room temperature, 500 and 1000 °C in air. The coefficient of friction of the ceramics was nearly constant regardless of sliding combinations and test temperatures. The specific wear rates at room temperature and 500 °C were high, usually of the order of 10−4 mm3/Nm, whereas low wear rates of the order of 10−5 or 10−6 mm3/Nm, or even mass gain, was observed at 1000 °C. SEM observations show that tribofilms are consistently formed on the wear surfaces. A porous tribofilm, generally associated with a high wear rate at room temperature or 500 °C, is formed by compaction of debris particles. A dense tribofilm with a flat and smooth surface, often associated with a very low wear rate of the order of 10−6 mm3/Nm or less at 1000 °C, is formed by plastic deformation accompanied by dynamic recrystallization at high temperatures. A locally dense tribofilm, associated with a low wear rate of the order of 10−5 mm3/Nm at 1000 °C, is formed from the sintering of the reattached debris at high temperatures.

An idea for obtaining unique identification (ID) numbers using polycrystalline silicon (poly-Si) thin-film transistors (TFTs) with a logic LSI compatible process is proposed. Like an actual human fingerprint, the characteristic variations of poly-Si TFTs are utilized for ID numbers in LSIs. The variation of poly-Si TFT characteristics is random, and this method offers unique, nonalterable, and nonduplicable numbers without any special processes, unlike other methods such as flash memory and mask ROM. These characteristics are highly suitable for ID number applications. The device physics of poly-Si TFTs for realizing the stable recognition of ID numbers was studied and a recognition circuit is proposed. The design guidelines for the grain size of poly-Si and AFD applications are also discussed.

The traditional water quenching technique used to evaluate the thermal shock resistance of ceramics is accompanied by an unstable heat transfer coefficient in the quenching process. This leads to an unreliable result of the value of the thermal shock strength of ceramics. Our purpose is to establish a new method using the laser irradiation technique by which the thermal shock strength of ceramics could be evaluated. Defining the laser power density, the so-called critical power density P L at which the ceramic specimen fractures, the method was evaluated both theoretically and experimentally for several structural ceramic materials. Since thermal shock fractures are caused by the induced thermal stress, the thermal shock strength must be correlated to the fracture toughness of ceramics. This study presents a relationship between the thermal shock strength P L , which corresponds to the critical powerdensity, by laser irradiation and the fracture toughness K IC by the indentation fracture technique for cer...

This paper presents a three-dimensional (3-D) topography simulator (3-D MULSS), and its applications. We focus on the description of the material surface and the algorithm of the surface advancement. Then we propose a 3-D topography simulation algorithm, with consideration of the probe size of observation, and based on the integration formula of the balance equation. Next, we show the simulation results of the 3-D MULSS: (1) isotropic deposition; (2) Aluminum-sputter deposition; (3) isotropic etching; (4) anisotropic etching; and (5) sequential process steps. These results make the accuracy of the 3-D MULSS clear, and also show that it is possible to stably simulate the sequential process steps.

A simple and accurate substrate current model that is valid in the whole operation region of a MOSFET with various dimensions is presented. The theory is based on hot-carrier induced impact ionization and band-to-band tunneling (BTBT). All the parameters in the model can be assigned proper physical meanings and are easily extracted from the measurement data. The model is incorporated in a Mitsubishi Circuit Simulator (MICS). Both the accuracy and the efficiency of the model are shown by experiment and simulation, and hence make the simulator useful for designers who care about low power applications. >

The volatile anesthetics enhance GABAergic inhibitory transmission at synaptic and extrasynaptic sites at central neurons. In the present study, we investigated the effects of three volatile anesthetics (isoflurane, enflurane and sevoflurane) on synaptic and extrasynaptic GABA(A) receptor responses using mechanically dissociated rat hippocampal CA1 neurons in which functional native nerve endings (boutons) were retained. The extrasynaptic GABA(A) receptors were activated by exogenous GABA application while synaptic ones were assessed by miniature and evoked inhibitory postsynaptic currents (mIPSCs and eIPSCs, respectively). All volatile anesthetics concentration-dependently enhanced the exogenous GABA-induced postsynaptic responses. The structural isomers, isoflurane and enflurane, increased mIPSC frequency while sevoflurane had no effect. None of these anesthetics altered mIPSC amplitudes at their clinically relevant concentrations. Sevoflurane prolonged event kinetics by increasing decay time of mIPSCs and eIPSCs at clinically relevant concentration. On the other hand, both isoflurane and enflurane only prolonged the kinetics of these events at 1 mM of high concentration. For GABAergic eIPSCs, both isoflurane and enflurane decreased the evoked response amplitude and increased the failure rate (Rf), while sevoflurane decreased the amplitude without affecting Rf. These results suggest that isoflurane and enflurane at the clinically relevant concentrations predominantly act on GABAergic presynaptic nerve endings to decrease action potential dependent GABA release. It was concluded that these anesthetics have heterogeneous effects on mIPSCs and eIPSCs with different modulation of synaptic and extrasynaptic GABA(A) receptors.

A mobility model for MOSFET device simulation is proposed. The model is not only applicable to both inversion layer and source/drain high concentration regions of a MOSFET, but it also takes into account the screening effect in the inversion layer. The model also includes an improved normal-field dependence for thin gate oxide MOSFETs. The low parallel electric field mobility is estimated by adding mobilities due to donor scattering, acceptor scattering and lattice scattering using Matthiesen's rule. Mobilities due to both the donor and the acceptor scattering include the electron screening effect. The mobility due to lattice scattering is formed as a function of normal electric field E/sub n/, including the strong dependence term of E/sub n/, to express surface roughness scattering. Calculation results of the device simulation using the mobility model show good agreement with the experimental data for various channel dopings. >

SummaryMulti-nucleated giant cells (MGCs; Langhans-type cell), formed from macrophage fusion, are recognized as a hallmark histological feature in chronic inflammation. However, their precise pathological role is still poorly understood, especially for microorganism pathogens in the neonatal immune system, which are capable of surviving intracellularly in phagocytes. To conduct a partial evaluation of the monocyte function of neonates, we investigated the ability of human cord blood monocytes to form MGCs in vitro by stimulating various cytokines and comparing them with adult peripheral blood monocytes. Monocytes from cord blood and adult peripheral blood were isolated and cultured for 14 days with cytokines known to induce MGC in vitro. The fusion index in experiments with a combination of interleukin (IL)-4 and macrophage colony-stimulating factor (M-CSF) and a combination of IL-4 and granulocyte–macrophage colony-stimulating factor (GM-CSF) was significantly lower in cord blood than in adult blood monocytes (P = 0·0018 and P = 0·0141, respectively). The number of nuclei per MGC was significantly lower in cord blood than in adult blood monocytes in experiments with IL-4 alone, the combination of IL-4 and M-CSF, and the combination of IL-4 and GM-CSF (P

We propose a new 2port (2P) SRAM with an 8T single-bit-line (SBL) memory cell for 45 nm SOCs. Access time tends to be slower as the device size is scaled down because of the random threshold-voltage variations. The Divided read Bit line scheme with Shared local Amplifier (DBSA) realizes fast access time without increasing area penalty. We also show an additional important issue of a simultaneous Read and Write (R/W) access at the same row by using DBSA with the 8 T-SBL memory cell. A rise of the storage node voltage causes the misreading. The Read End detecting Replica circuit (RER) and the Local read bit line with Dummy Capacitance (LDC) are introduced to solve this issue. A 128 BLtimes512WL 64Kb 2P-SRAM macro which cell size is 0.597mum2 using these schemes was fabricated by 45 nm LSTP CMOS process.

Generation behaviors at normal pressures and reactions of the oxygen radical anion (O- ion) have been studied. Highly concentrated O- ions which are encaged by a microporous crystal 12CaO · 7Al2O3 (C12A7) are emitted in the atmosphere with N2 gas at 975K or more and the emission speed is up to 1.7*10-7 mol/(s*m2). Emitted O- ions are easy to dissolve ion-exchanged water and it can make acidic water up to pH 2.9. The prediction of the existence of O- ions in low pH water as anion components is confirmed by ESR spectrum and anion liquid chromatogram. It is found that the O- ions have redox reactivity for a Si-surface, Nitroblue-Tetrazolium (NBT), and fungus disinfection ability.

An information management system concept with a web interface is proposed for integrating food recycling chain managements. The recycling problem is much discussed in various markets such as food, containers and packaging products, home appliances, construction materials, and automobiles. Although the word "recycling" is used over the different recycling field, the characteristic and the legislation of the recycling object are different in each field. It is necessary to understand the feature of requirements for information management systems to carry out an efficient, available recycling in each recycling field. In this paper, the requirements in the above recycling fields are compared and characteristic requirements especially for food recycling are extracted. And an information management system concept corresponding to these demands is proposed. This system has an integrative management interface which is designed to be opened to retail shops or recycling manufactures through a Web interface. Recycling information is stored in a database of the system directly through the recycling works and is used to get control over daily works, quality management of recycled feed materials, or to make reports to corresponding recycling law. Thus efficient and inexpensive information management for the recycled items can be realized

An information system concept with a Web interface is proposed for integrating recycle chain managements. In this paper, recycled items are consistently numbered by using RF-ID tags individually. Tag ID is directly read in each recycle chain and is sent to an integrative management system which is designed to be opened to retail shops or recycling manufactures through the integrative Web interface. Gathered information is stored in a database of the system and is used to make reports to corresponding recycling law or so. Thus efficient and inexpensive information management for recycled items can be realized.

This paper clarifies two SOI-specific leakage components, STI-induced punchthrough and gate-oxide leakage, found especially in large-scale integration, and proposes a new SOI technology: silicon-sidewall body-contact (SSBC). Without layout penalty and process complexity, SSBC realizes self-aligned body contact to the substrate, which suppresses gate-oxide leakage, and prevents the SOI body from being mechanically stressed, thus eliminating punchthrough leakage. SSBC is promising for scaled SOI CMOS LSIs.

A 3-dimensional process simulator based on an open architecture has been designed. A C++ like input language is designed to flexibly control process flow and to easily add user designed function. A self explaining data file format and its input/output C++ libraries are developed to ensure data exchange between the user's data file and HySyProS by using C++ class libraries. Several classes for discretizing and assembling drift-diffusion equations are developed for testing diffusion models efficiently.

A prototype system based on a multiple-access concept for moving pictures is presented. This system, multiple-access moving picture information system (MAMI-I), is expected to play a key role in the development of a commercial system that will provide visual database service or on-demand moving picture service. Key technologies for MAMI are discussed. Performance results obtained with a MAMI prototype and most of its practical applications are described. >

The speed advantage of SOI CMOSFETs has exclusively been claimed for front-end applications (Ajmera et al, 1999), but its potential for low-power applications has rarely been discussed. Recently, it was reported that BF (body floating)-enhanced short-channel effects increase V/sub t/-limited off leakage, for which V/sub t/ must be larger than bulk CMOS, thus resulting in no performance merit in the sub-0.2 /spl mu/m class (Chau et al, 1997). In this paper, we analyze the off leakage current I/sub off/ and aim to suppress I/sub off/ to the bulk level for low-power applications (I/sub off/ level /spl sim/10/sup -11/ A//spl mu/m). In such a low I/sub off/ regime, sub-0.2 /spl mu/m SOI has been found to suffer from another I/sub off/ component, i.e. GIDL (gate-induced drain leakage), especially for nMOSFETs. We show that lowering V/sub dd/ is very effective to reduce GIDL to a comparable level with bulk CMOS while still retaining a speed advantage and dynamic-power reduction.

A 49 year-old-woman was scheduled for resection of a huge hemangioma of the face and neck region. After the resection, severe edema developed on the tongue, larynx, and pharynx even leaving no space between the tracheal tube and these tissues. Prolonged respiratory management with endotracheal tube intubation was needed to maintain the upper airway for more than three weeks. Tracheostomy was performed 27 days after the operation. Two weeks later, the edema of the upper airway subsided. Thereafter her clinical course was uneventful, and she was discharged 22 days after the tracheostomy. Resection of a huge facial and neck hemangioma should be carefully managed as it can be followed by unexpected severe postoperative upper airway edema leading to suffocation.

A 49-year-old female with pemphigus vulgaris underwent the removal of a meningioma under general anesthesia. Neither bulla nor erosion was observed on her skin and oral cavity mucosa. She had been on prednisolone 15 mg for six years daily to avoid the recurrence of skin lesion. Anesthesia was induced and maintained with total intravenous anesthesia with propofol and fentanyl. No adverse episodes were encountered during the operative procedure. We checked the tracheal mucosa using bronchofiberscope before extubation. A small bulla was found on the tracheal mucosa, where the cuff of the tracheal tube was located. The trachea was extubated slowly under bronchofiberscopic observation, and no other bullae were found. It would have been formed by mechanical stimulation of the tracheal tube. This case suggests that we have to pay careful attention to the formation of bullae at any part of the body by mechanical stimuli during anesthetic management of patients with pemphigus vulgaris.

Background Definitive chemoradiotherapy (CRT) with 5-fluorouracil plus cisplatin (CDDP) is one of the most common treatment modalities for esophageal carcinoma (EC). However, there are limited data on CRT in elderly patients, and it is difficult for elderly patients to receive chemotherapy with CDDP due to various comorbidities and poor organ function, including poor renal function. The aim of this multicenter phase II study was to clarify the efficacy and safety of definitive CRT with docetaxel (DTX) in elderly patients. Methods Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) EC, PS 0-1, age over 70 years, and no desire for surgical treatment. A total of 40 patients were planned for enrollment. Chemotherapy consisted of 6 cycles of a 1-h infusion of DTX (10 mg/m2) repeated weekly. Radiation was concurrently applied at a dose of 60 Gy in 30 fractions. The primary end point was the 2-year survival rate. At this time, we evaluate the preliminary data of efficacy and safety of definitive CRT with DTX in elderly patients. Results A total of 16 patients were enrolled between July 2008 and January 2011, at which point, the trial was closed due to poor accrual. The median age was 77 years (range, 73–81); PS 0/1: 4/12; cStage IIA/IIB/III: 3/4/9. Fourteen patients (88%) completed CRT, one patient (6%) could not complete CRT because of severe toxic effects, and one (6%) refused to continue the treatment. The complete response rate was 37.5% (6 of 16). In this preliminary analysis, the median follow-up time was 19 months. The 1-year survival rate was 85.7%. The grade 3 or 4 toxic effects were esophagitis (31%), anorexia (13%), leukopenia (6%), neutropenia (6%), thrombocytopenia (6%), mucositis (6%), and infection (6%). No treatment-related deaths were observed. Conclusions These results suggest that CRT with DTX at this dose is not suitable for elderly patients with locally advanced EC due to severe toxicity.

Background The prognosis of gastric cancer with peritoneal metastasis is extremely poor. Neither systemic chemotherapy nor surgery alone prolongs survival of patients significantly. Methods Patients diagnosed with advanced gastric cancer underwent staging laparoscopy and received chemotherapy when peritoneal dissemination and/or cancer cells on peritoneal cytology were confirmed. The chemotherapy regimen consisted of S-1, weekly intravenous and intraperitoneal paclitaxel, which was verified in our phase II trial (Ann Oncol 2009). S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8. Clinical response of chemotherapy was assessed by computed tomography, gastroendoscopy, peritoneal cytology and second-look laparoscopy. Radical gastrectomy was carried out when macroscopic curative resection was made achievable by chemotherapy. Chemotherapy was restarted after operation as soon as possible. Overall survival, relapse free survival, morbidity and mortality of gastrectomy were evaluated. Results Out of 100 patients with peritoneal metastasis who received chemotherapy, 60 patients underwent gastrectomy after response to chemotherapy, including 54 with macroscopic metastasis and 6 with positive peritoneal cytology only. A median of three courses were administered preoperatively (range 1–16). Total or distal gastrectomy with lymphnode dissection was carried out in 54 or 6 patients, respectively. The median survival time was 34.5 months. The median relapse-free survival was 16.7 months. The first site of relapse was the peritoneum in 24 patients and the other organ site in 17 patients. Postoperative complications included anastomotic leakage and pancreatic fistula in two patients each, which were healed conservatively. There were no treatment-related deaths. Conclusions Gastrectomy combined with S-1, intravenous and intraperitoneal paclitaxel is safe and active for gastric cancer patients with peritoneal metastasis.

We use an angiofiberscope (AFS), an echocardiography (ECG) and a transesophageal echocardiography (TEE) as useful and productive tools for medical education perioperatively. We employed these monitors in the training of 5th-year medical students on general anesthesia in the operating room. A special intratracheal tube with small lumen (3 mm in diameter) for AFS (2.2 mm in diameter), was used for monitoring airway. Medical students are interested in and concentrate their attention on the monitor screen which has a continuous image from AFS. ECG was used routinely to evaluate preoperative cardiac function, while TEE was used during operation. These monitors play very useful role in medical education for students.

We have developed a three-dimensional integrated process simulator of topography and impurity: 3D-MIPS. 3D-MIPS includes topography and impurity simulator, which can simulate deposition, etching, photolithography, BPSG flow, ion implantation, oxidation and impurity diffusion. The diffusion model, in particular, uses a novel equation which unifies diffusion and segregation. In this paper, these models and their simulation results are presented, and we demonstrate that it is possible to simulate 3D-complicated structures stably.

Total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK) was given to over three thousand patients during four years from April 1989 through March 1993. The patients ranged in age from three months to eighty seven years. They underwent surgical, orthopedic, gynecological, thoracic, plastic and otolaryngeal surgeries, but patients who underwent craniotomy and obstetric operations were excluded. None of them developed any serious complications primarily due to DFK. DFK has many advantages such as the broad safety margin for three agents employed in DFK, no accident by N2O, no air pollution, empty bowels, no increase in middle ear pressure etc, while this has disadvantages such as high blood pressure, slow awakening from anesthesia and unpleasant dreams. Calcium channel blockers are very effective for antagonizing high blood pressure, and rapid recovery from anesthesia can be easily obtained by reducing ketamine dose given and also by application of epidural block. Intraoperative dreams may be avoided by concomitant use of benzodiazepines. Thus we are convinced that DFK can be a good as well as convenient anesthetic method for clinical anesthesia.

The complete amino acid sequence of the streptokinase (SKase) of Streptococcus pyogenes M type 12 strain A374, isolated from a patient with poststreptococcal glomerulonephritis (PSGN), was determined. The epitope domain for the monoclonal antibody N-59, which cross-reacts with SKases of both the PSGN-associated strain and S. equisimilis H46A (a non-PSGN-associated strain), was predicted to be localized in residues 370 to 374. The epitope domain specific for monoclonal antibody RU-1, which reacts only with the PSGN-associated SKase, was localized to residues 164 to 236.

The 8-kDa protein in Photosystem I (PS I) reaction center complex was isolated from a thermophilic cyanobacterium, Synechococcus elongatus, by SDS-polyacrylamide gel electrophoresis using TRIS-Tricine buffer system. The complete amino acid sequence of the protein was determined. The 8-kDa protein consisted of 73 amino acid residues giving a calculated molecular weight of 7,472. No significant sequence homology were observed with the known other small subunits in PS I reaction center complex, except for the 6.5-kDa protein in PS I from another thermophilic cyanobacterium, S. vulcanus. The 8-kDa protein was characteristically rich in hydrophobic amino acid residues, especially the content of leucine. These suggest that the 8-kDa subunit is an intrinsic structure component in PS I core complex for stabilization of the reaction center.

Four small subunits (14, 13, 10, and 8 kDa) of the photosystem I reaction-center complex were isolated from a thermophilic cyanobacterium Synechococcus elongatus. The complete amino acid sequence of the 10-kDa subunit was determined to consist of 80 amino acid residues giving a molecular mass of 8855.3, excluding iron and sulfur atoms, and containing two special sequences of cysteine residues, Cys-X-X-Cys-X-X-Cys-X-X-X-Cys-Pro, at residues 10-21 and 47-58, which indicates that the subunit is an apoprotein carrying two iron-sulfur centers, FA and FB, assigned as [4Fe-4S] clusters. The amino acid sequence indicated an 87.5% identity compared with those deduced from the nucleotide sequences of chloroplast gene psa C from several plants.

One of the small components (14 kDa) of the photosystem I reaction center complex was isolated from a thermophilic alga, Synechococcus elongatus. The amino acid sequence was determined. The protein consists of 137 amino acid residues, corresponding to the molecular mass of 15,319. Alignment of this sequence with the ferredoxin-binding proteins of photosystem I from other cyanobacteria and higher plants suggests the possible biologically important residues and the residues responsible for thermostability in the sequence.

We reported five cases of sudden onset of bradycardia and hypotension during spinal anesthesia in which measurable parameters of the patients were monitored continuously by inter-operating-room local area network system. In the first two cases, episodes of bradycardia and hypotension were caused by incomplete spinal blockade. In the third patient, severe bradycardia was preceded by gradual decrease of heart rate following high spinal blockade. In the last two cases of high spinal anesthesia, no remarkable change of the heart rate was observed before sudden onset of bradycardia and hypotension. All five patients were easily and adequately treated and they showed no signs of hypoxia. We would like to emphasize the importance of adequate and continuous monitoring during spinal anesthesia.

Intraoperative hypertension over 160 mmHg systolic observed during total intravenous anesthesia with droperidol, fentanyl and ketamine was treated with intravenous nicardipine in 50 surgical patients. Nicardipine was given intravenously in a bolus of either 0.5 mg or 1.0 mg to treat the intraoperative hypertension. Systolic and diastolic blood pressures decreased soon after administration of nicardipine without simultaneous sinus tachycardia. Thus rate pressure product was also reduced significantly. Neither preoperative hypertension, nor systolic blood pressure just before the administration of nicardipine had any significant relationship with hypotensive effect of intravenous nicardipine. We did not experience any adverse reaction with the drug. We conclude that intravenous nicardipine in a dose of 0.5-1.0mg can be given repeatedly to overcome hypertension observed during this method of anesthesia.

A simple and precise method has been developed for the analysis of plasma ketamine and its metabolites using gas chromatography with flame ionization detection after elution by trifluoroacetic dehydride. Seven surgical patients who received total intravenous anesthesia with droperidol, fentanyl and ketamine anesthesia over 5 hours were the subjects of the study. During the anesthesia, ketamine levels were from 1.0 to 2.0 micrograms.ml-1. After the termination of ketamine infusion, their levels decreased gradually. Metabolites I levels were elevated gradually to about twofold of that of ketamine and remained high. Metabolite II was detected in only two patients and their levels were under 0.2 micrograms.ml-1. The results of our study suggest that this type of anesthesia of prolonged duration is safe as judged by the present pharmacokinetic study.

Ten surgical patients who received various operative procedures including abdominal surgery and ENT surgery were the subjects of the pharmacokinetic study of total intravenous anesthesia with droperidol, fentanyl and ketamine. Six arterial samples were taken through an indwelling catheter in the left radial artery to measure plasma levels of ketamine and its metabolites by means of gas liquid chromatography. Two hours following the end of the ketamine infusion, plasma ketamine levels decreased to 14% of the control value (0.81 micrograms.ml-1), while metabolite I (K1) was still about 1.8 micrograms.ml-1 in the plasma. The control value of plasma ketamine just before the end of its infusion had not any significant relationship with the total dose of ketamine, total dose of fentanyl, blood loss or fluid given. The results of our study suggest that long continuous ketamine infusion would be safe as judged by its pharmacokinetics.

We have developed a new method of total intravenous anesthesia with droperidol, fentanyl and ketamine and have administered it to more than 400 surgical patients, ranging in ages from 4 to 80 years. Cardiac and neurosurgical patients were excluded. After establishing a routine monitoring, droperidol 0.06-0.1 ml.kg-1 was slowly given. After 5 minutes, fentanyl 1-2 micrograms.kg-1 and ketamine 1.0-1.5 mg.kg-1 were slowly administered intravenously. Trachea was intubated following intravenous succinylcholine. A total dose of 5-15 micrograms.kg-1 of fentanyl was given intravenously with a continuous infusion of ketamine 2 mg.kg-1.hr-1 during surgical procedure. Air and O2 (FIO2 0.30-0.35) were given and muscle relaxation was achieved with necessary dose of intravenous pancuronium or vecuronium and no inhaled anesthetic was given. Total intravenous anesthesia has many advantages such as no air pollution in the operating theatre, empty bowels, no organ (hepato-renal) toxicity, good peripheral perfusion and low cost, while this method has several disadvantages to overcome such as hypertension. There are many anesthetic agents for total intravenous anesthesia. However, sufentanil, alfentanil and propofol are not available. Droperidol, fentanyl and ketamine are the best combination for this purpose in Japan so far.

Three cases of anaphylactic shock were reported in which the core temperature was measured continuously. Two core temperature thermister probes were fixed on the forehead and the sole. Temperature dissociation between the core and the periphery disappeared in a few minutes after the administration of the causative agents. The clinical signs of the anaphylactic shock such as erythema, wheal and marked hypotension also developed in a few minutes after the disappearance of temperature dissociation. Thus treatment of anaphylactic shock could be started even before the patients develop severe hypotension. This clinical study suggests that a sudden disappearance of the temperature dissociation is a incipient sign of anaphylactic shock and to monitor the core as well as the peripheral temperature is a useful method for early diagnosis and treatment of anaphylactic shock.

Four small subunits (14, 13, 10, and 8 kDa) of the photosystem I reaction center complex were isolated from a thermophilic cyanobacterium Synechococcus elongatus and their N-terminal amino acid sequences determined. Sequence analysis of the 10-kDa subunit revealed that the distribution of cysteine residues, Cys-X-X-Cys-X-X-Cys-X-X-X-Cys-Pro, is characteristic of bacterial-type ferredoxins, and that its partial sequence is highly homologous to that deduced from the chloroplast gene frx A of liverwort. This indicates that the 10-kDa polypeptide is an apoprotein carrying two iron-sulfur centers, FA and FB, assigned as [4Fe-4S] clusters, which mediated the light-activated transfer of electrons from P700 in photosystem I reaction center complex to soluble ferredoxin. The amino acid sequence of the 14-kDa polypeptide also showed similarity to that of the 20-kDa polypeptide from spinach chloroplast that can be chemically crosslinked with soluble ferredoxin. Thus, the 14-kDa polypeptide appears to be the ferredoxin 'docking' protein.

We reported a 54-year-old male with essential thrombocythemia, who underwent coronary artery bypass grafting. Anesthesia was maintained with enflurane in nitrous oxide and oxygen supplemented with fentanyl. Heparin 7mg. kg-1 was administered intravenously to obtain adequate anticoagulant effect during 89 minutes of extracorporeal circulation. Aspirin and dipyridamole were also administered as anti-platelet therapy. No complications were observed during and after anesthesia. It is advocated that administration of anticoagulants such as heparin, aspirin and dipyridamole is effective to prevent thrombus formation.

The holes generated by impact ionization are spread over the vicinity of the source. At high drain biases, the hole density near the source is found to be larger than the impurity doping level by simulation. The highly concentrated holes decrease source potential barrier at high drain voltages and the source current is significantly increased.