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A glow discharge (GD) fusion neutron source that utilizes nuclear fusion reactions of deuterium has been upgraded. The fusion reactions in this device mainly occur by collisions between the charged or neutral particles and the hydrogen isotopes trapped at the surface of electrodes. In addition, it is known that the metal hydride coating on the electrode enhances the neutron production rate (NPR). Therefore, the elemental distribution, including deuterium, in the depth direction on the electrode is an essential factor in neutron production. However, the distribution on the electrode has not been experimentally investigated. This study aims to analyze the distribution experimentally and indicate the effect of the metal hydride coatings. To achieve this purpose, we prepared the titanium (Ti)-coated cathode and the uncoated cathode, of which the base material was stainless steel. After that, the neutron production test was performed in the range of from 5-to 40-mA currents and from 20-to 60-kV applied voltage. This test indicated that the NPR was improved by coating the cathode with Ti than the uncoated cathode. In addition, depth profiling on the cathodes by glow discharge optical emission spectroscopy (GD-OES) was performed. While the analysis indicated that the concentration of deuterium on both cathodes was increased after the test, there was no significant difference in the concentration of deuterium between both cathodes. Furthermore, the concentration of Ti on the Ti-coated cathode was vastly decreased. The cause of these changes needs to be investigated.

Trapping ions, such as deuterium and tritium, inside a potential well to generate neutrons is a well-established technology through electric and magnetic fields via the inertial electrostatic confinement fusion (IECF) and the tokamak, respectively. In the IECF, the straightforward configuration is a concentric cathode connected to a negative bias, surrounded by a grounded anode that serves as a vacuum vessel. Theoretically, neutrons are generated inside the vessel through fusion between ions that are accelerated by applying several tens kV voltage and tens mA current. Many parameters affect the plasma conditions and fusion in the system, hence the neutron production rate (NPR). This study investigates the cathode transparency and the number of apertures effect on NPR. For this end, eleven cathodes were fabricated from stainless steel in three different groups with different transparency and number of apertures. NPRs were investigated as a function of the cathode transparency and number of apertures at low power operating mode ∼1 kW. Experimental results revealed that higher NPR was produced from lower grid transparency and vice versa; this behavior was explained through beam–surface fusion with grid surface. In addition, a higher NPR was generated from the grid with many apertures; this was attributed to the effect of the deuterium ionization improvement by the number of ionizing electrons through the grid channels.

Aims: The study aimed to combine a metagenomics approach with complementary genetics to identify novel bacterial genes with orthologous functions, with the identification of novel RNase H genes as a test case. Methods and Results: A metagenomic DNA library was prepared from leaf-and-branch compost and used to screen for the RNase H genes by their abilities to complement the temperature-sensitive growth phenotype of the rnhA mutant Escherichia coli strain MIC3001. Determination of the nucleotide sequences of the cloned DNA fragments allowed us to identify 12 different genes encoding type 1 RNases H. Eleven of them encode novel RNases H, which show 40–72% amino acid sequence identities to those available from database. One of them lacks a typical DEDD/E active-site motif, which is almost fully conserved in various RNases H. Conclusions: Functional screening of environmental DNA without cultivation of microbes is a useful procedure to isolate novel RNase H genes. Significance and Impact of the Study: One of the identified RNase H genes had no sequence similarity to a previously assumed conserved motif, suggesting multiple catalytic mechanisms exist. This test case illustrates that metagenomics combined with complementary genetics can identify novel genes that are orthologous without sequence similarity to those from cultivated bacteria.

Atactic poly(vinyl alcohol) (at-PVA) and syndiotactic poly(vinyl alcohol) (st. PVA) prepared by gelation/crystallization using dimethyl sulphoxide/water mixtures were drawn in a hot oven at 160 °C under nitrogen. The degrees of polymerization of at- and st-PVA were 2000 and 1980, respectively. The drawability of at- and st-PVA films was affected by the composition of the solvent mixture as well as by quenching temperature. The drawability of at- and st-PVA films prepared by using the solvent mixture containing 60% of dimethyl sulphoxide and 40% of water became more pronounced as the temperature of gelation/crystallization decreased and the draw ratio reached maximum value at −80 °C. Namely, the greatest significant drawability was the same condition for at- and st-PVA films in spite of the different stereo-regularity. Even in this common best condition for significant drawability, however, the morphological properties of swollen gels and of the resultant dry gel films are different each other, dependent upon the tacticity. For at-PVA, small-angle light scattering under Hv polarization condition could not be observed in the swollen gels and in the dry films when the solutions were quenched at temperatures

One thousand two hundred fifty-four cases (610 colonic and 644 rectal cancers resected during 2 years from 1984 and followed up for more than 5 years) were entered from 140 institutions in Japan and analyzed by means of Cox's proportional hazards model. The analyzed pathologic variables were the size and depth of invasion, Dukes' stage, venous invasion, lymphatic permeation, and other clinical features, such as the sex and age of the patient and location of the tumor. The extent of dissection, serum carcinoembryonic antigen (CEA) level, and the presence or absence of adjuvant chemotherapy were also analyzed. Adjuvant chemotherapy consisted of three arms for both colonic and rectal cancers. For colonic cancer, arm I was a combination of i.p. (intraportal) and i.v. mitomycin C (MMC) + p.o. 5-fluorouracil (5-FU); arm II was i.v. MMC + p.o. 5-FU; and arm III was surgery only. For rectal cancer, arm IV was a combination of i.a. (inferior mesenteric artery) and i.v. MMC + p.o. 5-FU; arm V was i.v. MMC + p.o. 5-FU; and arm VI was surgery only. As for the factors affecting the disease-free survival of the patient, multivariate analysis disclosed nodal involvement, venous invasion, an elevated CEA level, and the lower part of the rectum. The effect of adjuvant chemotherapy on the patient's survival was proven for rectal cancer but not for colonic cancer. We conclude that these factors should be considered in setting the stage of tumor pre- and postoperatively.

The study aimed to combine a metagenomics approach with complementary genetics to identify novel bacterial genes with orthologous functions, with the identification of novel RNase H genes as a test case.A metagenomic DNA library was prepared from leaf-and-branch compost and used to screen for the RNase H genes by their abilities to complement the temperature-sensitive growth phenotype of the rnhA mutant Escherichia coli strain MIC3001. Determination of the nucleotide sequences of the cloned DNA fragments allowed us to identify 12 different genes encoding type 1 RNases H. Eleven of them encode novel RNases H, which show 40-72% amino acid sequence identities to those available from database. One of them lacks a typical DEDD/E active-site motif, which is almost fully conserved in various RNases H.Functional screening of environmental DNA without cultivation of microbes is a useful procedure to isolate novel RNase H genes.One of the identified RNase H genes had no sequence similarity to a previously assumed conserved motif, suggesting multiple catalytic mechanisms exist. This test case illustrates that metagenomics combined with complementary genetics can identify novel genes that are orthologous without sequence similarity to those from cultivated bacteria.

Ultrasonic motors have some special unique features, such as high-torque under low-speed operation, compact size, and no electromagnetic noise. Ultrasonic motors would be expected to apply an element of the artificial muscle. The driving principle of the ultrasonic motor is based on friction force between a rotor and a stator. Therefore, it is difficult to drive the ultrasonic motor at a constant speed, because the generation of heat by friction changes the friction force. In this study, we proposed speed controllers of the ultrasonic motor, considering the temperature rise of the ultrasonic motor. From the results, these methods were proved the most effective for the speed control of the ultrasonic motor in experiments.

We propose a spheroidal joint actuator using gyroscopic principle. This actuator has two features, which are the wide-range mobility of the multi DOF and releasing the overloaded external torque softly. The humanoid robots today, use an axis turn motor and various sensors for the parts of each joint. In the way of present situations, it is difficult to realize the motion ability like a human shoulder. Spheroidal joint actuators are used for a part of shoulder. In this paper, we describe a kinematics model and performance characteristics of a two-DOF actuator made as experiment constructed by a ball-and-socket joint and gyroscope, and prove result of experiment and consideration of a one-DOF actuator of simple model. By the trial production of spheroidal joint actuators, and various characteristic examinations, verify that it could operate. The flywheel characteristic was in agreement with the application kinematics model. At the torque characteristic examination, the maximum value of output torque is 2 kgf-cm.

In this paper, we propose a parallelized rule extraction method from trained neural networks for high-dimensional pattern classification problems. In the rule extraction method, we have to examine all combinations of antecedent fuzzy sets for extracting fuzzy rules. For high-dimensional problems, the number of possible combinations is increased exponentially. To address this difficulty, we parallelize the rule extraction method.

In order to perform parallel symbolic analysis for large electronic networks (including both numerical and symbolic parameters), a symbolic analysis algorithm is described using the upward hierarchical hybrid decomposition method and a parallel scheduling method of its analysis. This algorithm has the following properties: (1) the calculation time increases linearly with respect to the scale of networks; (2) it can be applied to edge decomposition and node decomposition as special cases; and (3) using parallel composition, larger scale networks can be analyzed faster. >

We retrospectively examined the changes in hemodynamics, oxygen index and renal function along with the complications in 25 patients who had undergone endovascular stent graft placement (ESG) surgery for abdominal aortic aneurysm. During stent graft placement, mean arterial pressure decreased to 58 +/- 8 mmHg by increasing the dose of anesthetics and/or using vasodilators. Except for this intended hypotensive period, mean arterial pressure and heart rate were relatively stable and adequately maintained during surgical manipulation. Oxygenation index was well maintained. A patient with a high preoperative creatinine level underwent prophylactic hemodialysis postoperatively. In other patients except one who died in early postoperative period, both BUN and creatinine levels were kept within normal ranges. Four patients died postoperatively and the causes of the death in two patients are related to the surgical procedure; one with multiple emboli possibly due to released atheloma from the aortic wall during procedure, the other with sepsis due to infected stent graft. Although ESG is a well tolerated procedure, embolism is the most serious complication. Careful preoperative evaluation of the ascending arch and descending aortic wall and monitoring with transcranial doppler are necessary.

The liver produces various cytokines, but local changes in the concentrations of these reaction products after liver surgery are unknown. We investigated the local changes of interleukin-6, interleukin-8 and interleukin-1 receptor antagonist after liver surgery.We determined levels of interleukin-6, interleukin-8, and interleukin-1 receptor antagonist in the hepatic vein and radial artery after liver resection in 13 patients. These cytokine levels in the portal vein were also measured in 6 patients.Interleukin-6, interleukin-8, and interleukin-1 receptor antagonist levels were significantly increased during liver surgery (P0.05). The level of interleukin-6 was significantly lower in the hepatic vein than in the radial artery as well as in the portal vein at the end of the operation (P0.05,0.03). The level of interleukin-8 and interleukin-1 receptor antagonist was significantly higher in the hepatic vein than in the artery (P0.05).Interleukin-6 may be taken up by the liver after liver surgery, and the difference between hepatic venous and peripheral arterial interleukin-6 levels may be an indicator of liver regeneration after liver resection. Interleukin-8 and interleukin-1 receptor antagonist appear to be produced in the remaining liver.

Intrathecal strychnine (glycine antagonist) or bicuculline (GABA(A) antagonist) yields a touch-evoked agitation that is blocked by N-methyl-D-aspartate receptor antagonism. We examined the effects of intrathecal strychnine and bicuculline on touch-evoked agitation and the spinal release of amino acids. Fifty-two Sprague-Dawley rats were prepared under halothane anesthesia with a lumbar intrathecal catheter and a loop dialysis catheter. Four days after implantation, rats were randomized to receive an intrathecal injection of N-methyl-D-aspartate (3 microg), strychnine (3 microg) or bicuculline (10 microg), or a combination of N-methyl-D-aspartate with bicuculline or strychnine. The agitation produced by brief light tactile stroking of the flank (tactile allodynia), and the spontaneous spinal release of glutamate, taurine and serine was measured. Intrathecal N-methyl-D-aspartate, strychnine and bicuculline produced similar touch-evoked allodynia. Intrathecal bicuculline and N-methyl-D-aspartate alone evoked a transient spinal release of glutamate and taurine, but not serine, in the 0- 10 min sample, while strychnine did not affect spinal transmitter release at any time. As GABA(A) but not glycine receptor inhibition at equi-allodynic doses increases glutamate release, while the allodynia of both is blocked by N-methyl-D-aspartate receptor antagonism, we hypothesize that GABA(A) sites regulate presynaptic glutamate release, while glycine regulates the excitability of neurons postsynaptic to glutamatergic terminals.

To investigate the mechanisms of cisplatin (CDDP)-resistance in neuroblastoma(NB), we established a CDDP-resistant human NB cell line, BM1R2.We characterized BM1R2 in terms of the susceptibilities to other anticancer agents, MDR1 and MRP expression, MYCN amplification, intracellular gultathione-S-transferase(GST-pi), metallothionein(MT) and gultathione(GSH) levels, and immunocytochemical and cytogenetic features.When compared to parent BM1 line, BM1R2 exhibited a 17.0-fold resistance to CDDP and cross-resistance to other agents. MRP expression was only observed in BM1R2, whereas MDR1 was expressed in both lines. Notably higher intracellular GST-pi and MT levels were observed in BM1R2 cells. MYCN amplifications were 50 and 6 copies in BM1 and BM1R2, respectively, and additional aberrations were observed in chromosome 1 and 2 in BM1R2.It was suggested that GST-pi and MT could exert crucial roles on CDDP-resistance in our system. BM1R2 is of great interest for investigating the mechanisms of CDDP-resistance in NB.

A new concept, "SIRS (systemic inflammatory response syndrome)", introduced for the use of innovative therapies in sepsis, indicates the importance of clinically satisfying services in the laboratories. Appropriate laboratory management of the host, parasite and environment, is needed for the diagnosis, treatment and prevention of sepsis. Improvement of environmental conditions is expected to contribute to the prevention of sepsis by nosocomial infections. Another important key in the management is quality assurance in blood cultures, which involves three issues that must be improved. Concerning the first two issues, high sensitivity and low contamination, balanced procedures must be performed to ensure cost-effectiveness. Regarding the third issue, we proposed a quick return system for positive blood cultures. We need to reconsider the traditional concept of "time" in microbiological tests and employ practical measures for sepsis in clinical laboratories.

Liver cells can produce nitric oxide from L-arginine through the action of nitric oxide synthase, but local changes in the concentrations of nitric oxide-related metabolites during liver surgery are not well characterized. We investigated such changes during and after liver surgery.We determined nitrite plus nitrate, L-arginine and L-citrulline concentrations in radial arterial and hepatic venous blood during and after liver surgery in 17 patients. Portal venous blood concentrations were also measured at the end of surgery in 7 patients.Both arterial and hepatic venous nitrite plus nitrate concentrations were significantly decreased during surgery and remained low compared to pre-operative values until post-operative day 2. Arterial and hepatic venous nitrite plus nitrate concentrations were not significantly different. L-arginine concentrations in both arterial and hepatic venous blood were significantly decreased during surgery, but returned to pre-operative levels on post-operative day 1. L-arginine concentrations in hepatic venous blood were significantly lower than in arterial blood. L-citrulline concentrations in both arterial and hepatic venous blood were significantly decreased during surgery compared to pre-operative values, and tend to be decreased until post-operative day 2. L-citrulline concentrations were significantly higher in hepatic venous blood than in arterial blood.Hepatic nitric oxide production was decreased peri-operatively during liver surgery. The decreases in L-arginine concentrations and in nitric oxide synthase activity may account for the decrease in nitric oxide production.

We investigated copy number aberrations in 29 primary tumors and 12 cell lines of esophageal squamous cell carcinoma (ESC) using comparative genomic hybridization. In the primary tumors, the most common sites of copy number gains were 3q26.3-27 (45%), 8q24 (41%), 5p15 (38%), Xq27-28 (38%), 14q32 (31%), 11q13 (28%), and 20q13.3 (28%). High-level gains (HLGs) indicative of gene amplifications were identified at 11q13 in two cases, and in one case each at 2q33-34, 3q25-29, 5p15.1-15.2, 7q21-22, 11p11.2, 12p11.2-12, and 13q34. Recurrent losses were observed only at 9p13(17.2%). In the 12 ESC cell lines, the most common sites of HLGs were 5p15.1-15.3 (four cases), 11q13 (four cases), 8q24.1-24.2 (three cases), 20q13.2-13.3 (three cases), 3q26.3 (two cases), and 7p15-22 (two cases). Less frequent HLGs (one case each) were observed at 2p16-22, 3q25, 7p12-14, 7q21-22, 9q34, 10q21, 11p11.2, 14q13-14, 14q31-32, 15q22-26, and 17p11.2. Chromosomes and chromosome arms that showed frequent losses in the cultured lines were 18q (58%), 4 (50%), 9p (50%), and 3p (42%). These findings provide evidence for a number of previously unknown genomic aberrations in ESC, suggesting target regions for positional cloning of genes relevant to carcinogenesis in the esophagus. In particular, we identified a significant amplification of the DPI gene (TFDPI), a transcription factor that forms heterodimers with E2FI, in the single primary tumor that exhibited HLG at 13q34.

We used comparative genomic hybridization to study malignant fibrous histiocytomas (MFHs) from 19 patients to detect changes in the copy number of DNA sequences, along entire chromosomes. Together with losses and gains in various chromosomal regions, distinct high-level amplifications were found at six loci (4q12-21, 8p21-pter, 8q24.1-qter, 9q12-13, 12p11.2-pter, and 15q11.2-15), suggesting that those regions may contain unknown (proto) oncogenes. We focused on the 8p amplicon, where detailed characterization allowed us to determine that the minimal common amplified region lay between markers D8S1819 and D8S550 at 8p23.1. A novel gene designated MASL1 (MFH-amplified sequences with leucine-rich tandem repeats 1) was isolated from within this narrowly defined region. Expression of the MASL1 gene was enhanced significantly in MFH tumors bearing the 8p amplicon. The primary structure of its deduced product revealed an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, all of which are important structural or functional elements for interactions among proteins related to the cell cycle. These features suggest that overexpression of MASL1 might well be oncogenic with respect to MFH.

The ratio of effective arterial elastance (Ea) to left ventricular elastance (Ees) is an indicator of the coupling between ventricular properties and arterial load properties. Another criterion for the coupling between an energy source and its load is the principle of economical fuel consumption, or mechanical efficiency, which is defined as the ratio of stroke work (SW) to myocardial oxygen consumption per beat (MVO2). It has been revealed that SW of ventricular contraction is maximized when Ea/Ees = 1, while mechanical efficiency is maximized when Ea/Ees = 0.5. The purpose of the present study was to investigate the ventriculo-arterial coupling during hypertension, and the effects of nicardipine on this relationship in surgical patients using Ea/Ees and SW/MVO2 as indicators. Anaesthesia was maintained with isoflurane, nitrous oxide, and fentanyl. Radial artery pressure was displayed on a polygraph, and left ventricular end-systolic and end-diastolic volumes were determined by use of transoesophageal echocardiography. Ees was calculated as MAP/(ESVI-4), where MAP is mean arterial pressure and ESVI is end-systolic volume index. Ea was calculated as the ratio of MAP to stroke volume index (SVI). Stroke work index (SWI) was calculated as the product of MAP and SVI. MVO2 was assessed by estimating the ventricular pressure-volume area index (PVAI), which is expressed as the sum of SWI and the end-systolic potential energy index. Before (baseline), and 3, 10, 20, and 30 min after i.v. nicardipine (30 micrograms kg-1), Ea/Ees and SWI/PVAI were determined in 14 surgical patients with intraoperative hypertension. Before nicardipine (during hypertension), Ea was almost equal to Ees, whereas Ea/Ees was significantly reduced to about 0.5-0.6 at 3, 10, and 20 min after nicardipine. SWI/PVAI was maximized and significantly greater than the baseline value at 3 min after nicardipine. These results suggest that, during hypertension, ventricular and arterial properties were so matched as to maximize SW at the expense of the work efficiency, whereas mechanical efficiency of ventricular contraction was maximized after nicardipine.

The purpose of this study was to assess perioperative changes in psychological features of patients receiving anesthesia and operation. Anxiety level and desire for obtaining information were evaluated in 37 patients using the Amsterdam preoperative anxiety and information scale (APAIS) at three points: before and after the preanesthetic examination, and 3 to 5 days after the operation. Anxiety scale (4-20) and information scale (2-10) scores decreased postoperatively from 9.8 +/- 3.8 to 7.3 +/- 3.4 and from 6.1 +/- 2.1 to 4.1 +/- 1.9, respectively. There was a significant but weak correlation (rs = 0.35) between the anxiety scale and information scale before the preanesthetic examination. The postoperative information scale score correlated well with preoperative anxiety scale score (rs = 0.61), and this correlation was higher than with preoperative information scale score (rs = 0.37). When patients were divided into two subgroups, namely patients with (U, n = 12) or without (non-U, n = 25) an increase in postoperative information scale score, anxiety scale score before the preanesthetic examination tended to be higher and the postoperative anxiety scale score was significantly higher in the U group than in the non-U group. We conclude that we should provide more information to the patients who have higher anxiety scale score before the preanesthetic examination regardless of their degree of desire for information.

The prognostic factors and natural history of recurrence in patients with colorectal carcinoma who underwent curative resection and no other therapy were analyzed.The object of analysis was the potentially curative resection only subgroup in the randomized clinical trial (RCT) that we performed. Cox's proportional hazards model was used mainly to analyze recurrence rates during the first 5 years after surgery.The analysis was performed on a subgroup of the RCT (279 patients with colon carcinoma and 293 patients with rectal carcinoma). Five-year disease free survival rates were 76.3% and 56.5% for colon and rectal carcinomas, respectively. The prognostic factors for recurrence for colon carcinoma patients were different from those with rectal carcinoma. For colon carcinoma, only Dukes stage was significant, whereas for rectal carcinoma, Dukes stage, age, location of the tumor, and serosal and venous invasion by cancer cells were prognostic factors. Log-transformed disease free survival rates were linear in Dukes Stage B and biphasic in Dukes Stage C for both colon and rectal carcinoma. The two phases in Dukes Stage C intersected at 2.85 and 3.04 years, respectively. The annual hazard value was high for the first 3 years in both colon and rectal carcinoma.We conclude that follow-up of patients with colorectal carcinoma who undergo potentially curative resection is of particular importance in the first 3 years after surgery. Furthermore, the usefulness of adjuvant chemotherapy can be adequately evaluated from data yielded during this postoperative period.

A multi-center collaborative study was conducted in curatively resected gastric cancer patients at Stages II and III to compare oral 5-FU (Group A), oral Tegafur (Group B) and i.v. MMC + oral 5-FU (Group C). From May 1982 to April 1985, 1,012 cases were enrolled at 55 institutions. Some 138 (13.8%) were excluded, and 874 were analyzable. In the analysis of background factors, Group B had more cases with tumor of large diameter and advanced Stage. Adverse effects were relatively mild in all groups, and there was no problem in drug tolerance. Five-year survival rate was 67.6%, 62.4% and 68.6% in Groups A, B and C, respectively, reflecting no significant difference among them. It was 85.0%, 83.0% and 81.1% in Stage II and 52.5%, 51.0% and 59.0% in Stage III of Groups A, B and C, respectively. No significant difference was found, but Stage III of Group C showed a slightly higher survival rate. Supportive clinical study will be required to assess the usefulness of MMC as an introduction therapy. We found no difference in efficacy between 5-FU and Tegafur as maintenance therapy. The life-prolongation effect of fluoropyrimidines in comparison with surgery alone should be studied separately.

To investigate coupling between the heart and arterial system in patients undergoing elective non-cardiac surgery, we determined both the ventricular elastance and the effective arterial elastance in two groups of subjects: normal group, 68 subjects without heart disease; and cardiac group, 33 subjects with heart disease. Left ventricular end-systolic (Ves) and end-diastolic (Ved) volumes were determined by transesophageal echocardiography. By assuming that left ventricular end-systolic pressure (Pes) is close to mean arterial blood pressure (MAP) and that x-axis intercept (Vo) is zero, the ventricular elastance (E'max) was approximated as MAP/Ves, and the effective arterial elastance (Ea) as MAP/(Ved-Ves). In 222 (74%) of the 299 measurements obtained in normal group, Ea/E'max was nearly 0.5, which is a condition for a maximal mechanical efficiency, while in 61 measurements (20%) Ea was almost equal to E'max (Ea/E'max = 1), which is a condition for maximal stroke work from a given end-diastolic volume. In contrast, in cardiac group, Ea/E'max was nearly 0.5 in 56 (41%) of the 137 measurements, while in 42 measurements (31%) Ea/E'max was nearly 1. In addition, although the value of Ea/E'max over 2, which represents severe heart failure, was not observed in normal group, Ea/E'max was over 2 in 10 measurements (7%) in cardiac group. Thus, the present results suggest that, as reported previously in awake patients, ventriculoarterial coupling is set toward higher left ventricular work efficiency in surgical patients without heart disease, whereas in patients with heart disease, ventricular and arterial properties are so matched as to maximize stroke work at the expense of the work efficiency.

Depressant effects of halothane, enflurane and isoflurane on isolated guinea-pig left atrial muscles bathed in Tyrode's solution at 30 degrees C were examined. Contractions were elicited by stimulation through external field electrodes while tension was recorded continuously. Frequency-force relationships at stimulation rates of 0.1, 0.2, 0.5 and 1 Hz were studied. The pD2 values of these volatile anesthetics at each stimulation rates were not different significantly, suggesting the frequency-independent depressions of these anesthetics. Interval-strength relationships at time intervals of 0.3-20 sec during 1 Hz-stimulation were also studied. Mechanical restitution curves after converting to logistic function reached a peak at 8-20 sec and were fitted well to double exponential functions with time constants of 200-600 msec (k1) and 2-6 sec (k2). All volatile anesthetics depressed the magnitude constants for fast response in a dose dependent manner. Accordingly, at high concentrations, mechanical resuscitation curves tended to fit single exponential function. Halothane and enflurane did not alter time constant k1, k2 significantly, while isoflurane increased k2 significantly. These results suggest that the mechanisms of myocardial depressant effects are different between these anesthetics.

Long-term oral administration of fluoropyrimidines such as 5-fluorouracil (5-FU) or tegafur is commonly used as an adjuvant chemotherapy for gastric cancer, but the optimal period or optimal total doses of fluoropyrimidines have not been studied. Two hundred cases of macroscopical Stage II and III curatively resected gastric cancer patients were entered in this study, and divided into three groups (6 months group: mitomycin C was given i.v. at day 0 and day 1 and 5-FU tablets were orally administered at a dose of 200 mg/day for 6 months. 12 months group: MMC was given the same as for the 6 months group and 5-FU tablets were administered for 12 months. Surgery alone group: No chemotherapy, operation only). As the result, 185 cases were eligible. There was no significant difference between the 6 months group and the 12 months group among Stage II patients. Although there was also no significant difference between the 2 groups in Stage III patients, the survival curve of 12 months group was always higher than in the 6 months group. When comparing with surgery alone group, 5-year survival of the 12 months group was always higher than in the surgery alone group of Stage III patients; however, the survival rate in the 6 months group was worse than in the surgery alone group at Stage II and III. These results suggest that MMC i.v. and 12 months or over administration of 5-FU tablets is useful for Stage III gastric cancer patients, and that cooperative study is required comparing with surgery alone in Stage II patients.

Changes in pial vessel diameter combined with regional cerebral blood flow (CoBF) during infusion of vasodilating drugs, isosorbide dinitrate (ISDN) 5 micrograms/kg/min and nitroprusside (NTP) 5 micrograms/kg/min, compared with haemorrhagic hypotension were studied in cats anesthetized with halothane (1.0%). Pial arteries and veins were measured by image-splitting technique and were each divided into three groups according to the reference diameter: I;50 microns, II; 51microns100, III; 101microns. With either drug, the mean blood pressure (mBP) decreased by 10-20%. There was significant decrease in cerebral vascular resistance with ISDN compared with haemorrhagic hypotension while CoBF (H2 clearance) remained unchanged. Dilatation of pial arteries depending on vessel size with ISDN was two-hold compared with haemorrhagic hypotension without any change in all veins. Consistent and significant dilation of veins (I and II) was observed only during NTP infusion. These findings indicate the differential effect of ISDN and NTP on pial arteries and veins.

We determined both the slope of the left ventricular end-systolic pressure-volume relation (Emax), which is a measure of contractility independent of loading conditions, and the slope of the arterial end-systolic pressure-stroke volume relation (Ea), which is a measure of arterial load independent of ventricular function, in 10 patients undergoing elective noncardiac surgery. Left ventricular end-systolic volume (Ves) was measured by transesophageal echocardiography and instantaneous left ventricular end-systolic pressure (Pes) was estimated from the dicrotic notch pressure in the radial artery. Emax was calculated during afterload reduction (nicardipine 30 micrograms.kg-1 iv), and the correlation of Emax to either Pes/Ves ratio or MAP (mean arterial blood pressure)/Ves ratio was accomplished in order to investigate whether these indices were clinically useful measurements of ventricular function or not. Ea was also calculated from the data obtained before and 2-3 min after nicardipine iv. The averaged Emax and x-axis intercept (Vo) were 3.11 mmHg.ml-1 and -3.8 ml, respectively. The correlation coefficient obtained between Emax and Pes/Ves was 0.96, and that obtained between Emax and MAP/Ves was 0.97. Ea decreased significantly (P0.05) following intravenous nicardipine, demonstrating a decreased arterial load. The direction of changes in Ea was similar to that reported previously in systemic vascular resistance. From these results, we conclude that measurement of Emax (or Pes/Ves, MAP/Ves) and Ea using transesophageal echocardiography and radial artery pressure tracing is feasible and these are a useful tool to estimate left ventricular performance and arterial load during surgery.

In toroidal plasmas immersed in a toroidal field of B, the electrons drift downward, while the ions drift upward due to the field gradient and curvature. The electrons that have reached the bottom wall return through the conducting vessel to the top, on which they recombine with the ions, completing the current circulation. Helical field lines by the superposition of a vertical field BZ provide another return path of internal current circulation, along which the electrons flow toroidally, generating a toroidal current. These conjectures have been examined on electron cyclotron resonance (ECR) plasmas in the Low Aspect ratio Torus Experiment (LATE) device with current-collecting electrodes at the top and bottom of the vacuum chamber. Upon the blocking of the external return path, the discharges terminate when BZ = 0, while they survive with a toroidal current when BZ is applied, showing that current circulation is vital to maintain the discharge. Detailed studies reveal the characteristics of current circulation and equilibrium. When BZ = 0, the electron pressure profile is a uniform vertical ridge along the ECR layer in accordance with the electron vertical drift current circulating via the external circuit, while an upwardly shifted potential hill arises, providing the ions E × B drift paths around the potential peak to the vicinity of the top electrode. When BZ is applied, the central electron pressure rises with an upwardly shifted peak, being relaxed from the vertical uniformity by addition of the internal return circuit. The space potential VS decreases and the electron density obeys the Boltzmann law under VS. The vertical and toroidal currents are found to be equilibrium currents driven by the base and excess portions of electron pressure, respectively, to ensure the radial force balance of the plasma torus.

Suppose an axisymmetric toroidal plasma is immersed in a toroidal magnetic field B in the cylindrical coordinates of (R, , Z) with Z coordinate on the symmetric axis. The electrons drift downward while the ions drift upward due to the field gradient and curvature by the velocity, . It was conjectured that the electrons that reached the bottom wall flowed through the conducting vessel to the top where they recombined with the ions, thus a closed circuit being completed for the vertical charge-separation current. This current has for the first time been directly measured by current-collecting electrodes newly fabricated in the Low Aspect ratio Torus Experiment (LATE) device for a plasma maintained by a microwave power at the electron cyclotron range of frequency. The amount of current is found to be consistent with the above vertical drift model for electrons. The discharge terminates quickly during microwave injection when the current circuit is blocked by the artificial insertion of a large resistance.

Effects of ergot alkaloids, nicergoline (NIC), on survival rate, brain water content, local cerebral blood flow (LCBF: 14C-iodoantipyrine) and glucose utilization (LCGU: 14C-2-deoxyglucose) were examined after bilateral carotid artery occlusion (BCAO) in spontaneously hypertensive rats. Two series of study were performed; the permanent BCAO and 3-hr-BCAO study. After permanent BCAO, the survival rate at 24 hrs of 32% (8 mg/kg, i.p.) or 38% (16mg/kg) in NIC group was higher than that in non-treated group (12%). At the end of 3-hr-BCAO, the increase in water content (dry-wet) in di-mesencephalon was less in NIC (100 micrograms/kg/min, i.v.) group than that in non-treated group. The decrease in LCBF in caudate-putamen (CP), parietal cortex (PC), thalamus (TH), hypothalamus (HT), and substantia nigra (SN) were less in NIC group than those in non-treated group. At the 2-hr-reperfusion after 3-hr-BCAO, the decrease in LCBF in TH and HT were less in NIC group than those in non-treated group. The LCGU in sensory motor cortex, CP, PC, HT, inferior colliculus and pons-reticular were higher in NIC group than those in non-treated group. From these results, it is concluded that nicergoline may have ameliorative effects on survival rate related to the prevention of decreased cerebral blood flow and metabolism following brain ischemia.

The effects of isosorbide dinitrate (ISDN) on regional cerebral blood flow (rCBF) and intracranial pressure (ICP) were examined in cats. A low dose of ISDN (2.5 micrograms/kg/min) infusion did not show any changes in cerebral hemodynamics. During high dose of ISDN (5.0 micrograms/kg/min) or NTP (5.0 micrograms/kg/min) infusion, mean blood pressure (mBP) decreased by 10 to 20% accompanied by decreased cerebral perfusion pressure (CPP: mBP-ICP), however, rCBF or ICP did not change. It is concluded that intravenous administrations of ISDN in a dose of 2.5-5.0 micrograms/kg/min that produce slight decrease in blood pressure did not influence on cerebral hemodynamics.

As one of the fundamental studies of the pre-operative chemotherapeutic methods in 22 cases with colonic cancer, we studied a progress of the concentration in blood and concentration in tissues including those in the portal vein after administration of UFT. The concentration of 5-FU in blood reached to the peak at 2 hours after administration of UFT and then decreased rapidly, while it was maintained for a long term in comparing with that of 5-FU (oral remedies; tablet and dry syrup). This fact suggested that UFT can be expected for metastatic inhibition and prevention of the recurrence because it showed an effect in free-cancerous cells before and during operation. The anti-tumorous effect was also expected because the concentration of 5-FU in cancerous tissues was significantly higher than that in non-cancerous region. In our study in this time, down staging was considered by pre-operative chemotherapeutic method of colonic cancer in the future because concentration of 5-FU was also highly obtained in metastatic lymph nodes. From the above-mentioned results, pre-operative chemotherapeutic method using UFT was expected as a part of the intensive therapies.

We studied the effects of lidocaine and MEGX on the sodium current, using Vmax as an indicator, at an extracellular potassium concentration ([K]o) of 10 mmol.l-1, and compared the present results with those obtained at 5.4 mmol.l-1 [K]o in our previous study. At 10 mmol.l-1 [K]o, both lidocaine (10 micrograms.ml-1) and MEGX (10 micrograms.ml-1) significantly decreased the Vmax at the steady-state of 1 Hz, caused a significant rate-dependent decrease in Vmax, and slowed the recovery kinetics of Vmax. These effects of both agents were more prominent than those obtained at 5.4 mmol.l-1 [K]o, suggesting that MEGX as well as lidocaine produce voltage-or [K]o-dependent blocking effects on Vmax.

The cerebral effects of hypotension induced by inhalation of increasing concentrations of isoflurane or intravenous administration of prostaglandin E1 (PGE1) were studied in 15 dogs anesthetized with 1% isoflurane and 50% nitrous oxide during normocarbic (PaCO2 approximately 39 mmHg) and normothermic (37.5 degrees C) condition. Mean arterial pressure (MAP) was decreased stepwise to 25, 40, and 55% of its baseline values. Cerebral blood flow (CBF) was measured using the venous outflow technique. Cerebral metabolic rate for oxygen (CMRO2), cerebral metabolic rate for glucose (CMRgl) and oxygen/glucose index (OGI) were calculated, and cerebrospinal fluid pressure (CSFP) and EEG were also recorded at each decrement in MAP and after resuming the control condition. The CBF, CMRO2, CMRgl, OGI and CSFP responses related to hypotension showed no significant changes from baseline values in both methods. However, CBF values in isoflurane-induced hypotension at 25% and 40% reduction of MAP were significantly higher than those in PGE1-induced hypotension. By increasing concentration of isoflurane, EEG changed from continuous fast wave to high amplitude (100 microV) slow wave (4-6 Hz) and typical burst suppression observed in 3 of 8 dogs. In contrast, no significant EEG changes were seen during PGE1-induced hypotension. These results suggest no adverse effect of isoflurane- and PGE1-induced hypotension on cerebral metabolism or function.

The effects of ONO-1016, as an inhibitor of C1-/HCO3-exchange, on the brain edema and circulatory failure following cerebral ischemia were examined in stroke-prone spontaneously hypertensive rats (SHR-SP). SHR-SP were divided into three groups: control (sham-operation), non-treated, ONO-1016 group, respectively. Cerebral ischemia was produced by bilateral carotid artery occlusion (BCAO) for 1 hr and then following reperfusion. The brain water content and local cerebral blood flow (LCBF) were determined by dry-wet method and 14C-iodoantipyrine method 2 hr after start of reperfusion. ONO-1016 was given intravenously at a dose of 100 micrograms/kg/min prior to ischemia. The brain water content increased in septum (SP), amygdala (AM) in both non-treated and ONO-1016 groups compared from those in control group. However, brain water contents in SP and midbrain were lower in ONO-1016 group than those in non-treated group. LCBFs decreased to 50-80% in SP, cerebral cortex (CT), striatum (ST), hippocampus (HC) and AM in non-treated group, while LCBFs decreased to 60-80% in SP, CT, ST, AM in ONO-1016 group when compared from those in control group. Decrease of LCBF in ST and HC in ONO-1016 group were less severe than those in non-treated group. From these results, ONO-1016 may prevent the brain edema formation associated with hypoperfusion during reperfusion period after ischemia in SHR-SP.

We evaluated the relation between dose and response for the neuroprotective effect of propofol in a rat model with incomplete cerebral ischaemia. For clarification of the mechanism of neuroprotection, plasma catecholamines and tumour necrosis factor-alpha levels were measured. Three doses (low, moderate and high-dose) of propofol were tested. These produced, respectively, a low amplitude, slowing and a burst-suppression pattern of electroencephalographic activity. Incomplete cerebral ischaemia was produced by right carotid artery occlusion combined with haemorrhagic hypotension (35 mmHg) for 30 min. Neurological outcome at 72 h post-ischaemia in the high-dose group was significantly better than that in both low-dose and moderate-dose groups. Propofol exhibited a trend in the dose-related attenuation of the increases in plasma adrenaline and noradrenaline during ischaemia. Tumour necrosis factor-alpha increased during and after ischaemia in all groups with no intergroup differences. The results indicate that a burst-suppression dose of propofol provides neuroprotection. The protective effect can not be completely explained by the attenuating effect on circulating catecholamines.