Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.     

The combined method: a novel access technique for fetal endoscopic surgery

BACKGROUND/PURPOSE: To develop practical and less invasive techniques for fetal endoscopic surgery, new methods of lifting the uterine wall to allow fetal surgery without maternal laparotomy were developed and assessed. METHODS: Fetal endoscopic surgical procedures, including tracheostomy and umbilical vascular cannulation, were performed using one of the three methods to enter the uterus without maternal laparotomy in pregnant goats (n = 6; 105 to 115 days' gestation): (1) direct uterine lifting with an air-cushion device; (2) indirect uterine lifting, in which the uterine wall was fixed to the maternal abdominal wall using balloon tip ports inserted percutaneously by Seldinger's method, then the maternal abdomen was lifted mechanically; and (3) combined method, in which low pressure CO2 (5 mm Hg for initial inflation and 2 mm Hg for maintenance) was insufflated into the uterus in addition to the indirect uterine lifting cited above. RESULTS: The direct uterine lifting caused massive injury of myometrium and uterine membranes. The creation of intrauterine space and the protection of the membranes were not accomplished effectively by the indirect uterine lifting only. The combined method provided the adequate intrauterine space and excellent endoscopic visibility for completion of the endoscopic procedures with minimal uterine injury. CONCLUSION: The fetal endoscopic surgery may be accomplished simply and safely by the combined method, a novel technique of uterine lifting to allow fetal surgery without maternal laparotomy.     

Localization of Rho GTPase in sea urchin eggs

OBJECTIVE: Previous studies in our laboratory showed that the platelet anti-aggregating effect exerted by insulin, mediated by a nitric oxide (NO)-induced increase of guanosine-3',5'-cyclic monophosphate (cGMP), is lost in the insulin-resistant of obesity and obese NIDDM. It is not clear 1) whether the alterations observed in obese NIDDM patients are attributable to the obesity-related insulin resistance or to diabetes per se and 2) whether insulin-resistant states present a normal or a blunted response to NO. This study has been conducted to investigate 1) the platelet sensitivity to insulin in lean NIDDM and 2) the platelet sensitivity to an NO donor, glyceryl trinitrate (GTN), in obesity and in both lean and obese NIDDM. RESEARCH DESIGN AND METHODS: We determined 1) ADP-induced platelet aggregation and platelet cGMP content in platelet-rich plasma (PRP) obtained from 11 lean NIDDM patients, after a 3-min incubation with insulin (0, 240, 480, 960, 1,920 pmol/l) and 2) ADP-induced platelet aggregation and platelet cGMP content in PRP obtained from 9 obese subjects, 11 lean and 8 obese NIDDM patients, and 18 control subjects, after a 3-min incubation with 0, 20, 40, and 100 mumol/l GTN. RESULTS: Insulin dose-dependently decreased platelet aggregation in lean NIDDM patients (P = 0.0001): with 1,920 pmol/l of insulin, ADP ED50 was 141.5 +/- 6.4% of basal values (P = 0.0001). Furthermore, insulin increased platelet cGMP (P = 0.0001) from 7.5 +/- 0.2 to 21.1 +/- 3.7 pmol/10(9) platelets. These results were similar to those previously described in healthy subjects. GTN reduced platelet aggregation in all the groups (P = 0.0001) at all the concentrations tested (P = 0.0001), but GTN IC50 values were much higher in insulin-resistant patients: 36.3 +/- 5.0 mumol/l in healthy control subjects, 26.0 +/- 6.0 mumol/l in lean NIDDM patients (NS vs. control subjects), 123.6 +/- 24.0 mumol/l in obese subjects (P = 0.0001 vs. control subjects), and 110.1 +/- 19.2 mumol/l in obese NIDDM patients (P = 0.0001 vs. control subjects). GTN dose-dependently increased platelet cGMP in all the groups (P = 0.0001 in control subjects, lean NIDDM patients, and obese subjects; P = 0.04 in obese NIDDM patients). Values reached by obese subjects and obese NIDDM patients, however, were lower than those reached by control subjects (with 100 mumol/l of GTN, P = 0.001 and P = 0.0001, respectively). In healthy control subjects and in obese subjects, the insulin:glucose ratio, used as an indirect measure of insulin sensitivity, was positively correlated to GTN IC50 (r = 0.530, P = 0.008), further suggesting that the sensitivity to NO is reduced in the presence of insulin resistance. CONCLUSIONS: The insulin anti-aggregating effect is preserved in lean NIDDM; platelet sensitivity to GTN in preserved in lean NIDDM but is reduced in the insulin-resistant states of obesity and obese NIDDM. Resistance to nitrates, therefore, could be considered another feature of the insulin-resistance syndrome.     

Strongyloidiasis associated with nephrotic syndrome

We report a nephrotic syndrome patient with eosinophilia who developed ileus, epigastralgia and malabsorption due to strongyloidiasis which became symptomatic by steroid therapy. The patient was then treated with thiabendazole and recovered. A percutaneous renal biopsy revealed minimal change nephrotic syndrome. This renal injury may be brought on by severe infection of Strongyloides stercoralis. It is important to rule out strongyloidiasis prior to corticosteroid therapy to patients from eosinophilia endemic areas.     

Preparation of TiB2 sintered compacts by hot pressing

A sintered compact of titanium diboride (TiB₂) was prepared by hot pressing of the synthesized TiB₂ powder, which was obtained by a solid-state reaction between TiN and amorphous boron. Densification of the sintered compact occurred at 20 MPa and 1800° C for 5 to 60 min with the aid of a reaction sintering, including the TiB₂ formation reaction between excess 20 at % amorphous boron in the as-synthesized powder (TiB₂ + 0.2B) and intentionally added 10 at % titanium metal. A homogeneous sintered compact of a single phase of TiB₂, which was prepared by hot pressing for 30 min from the starting powder composition [(TiB₂ + 0.2B) + 0.1 Ti], had a fine-grained microstructure composed of TiB₂ grains with diameters of 2 to 3 m. The bulk density was 4.47 g cm^–3, i.e. 98% of the theoretical density. The microhardness, transverse rupture strength and fracture toughness of the TiB₂ sintered compact were 2850 kg mm^–2, 48 kg mm^–2 and 2.4 MN m^–3/2, respectively. The thermal expansion coefficient increased with increasing temperature up to 400° C and had a constant value of 8.8 x 10^–6 deg^–1 above 500° C.     

Effect of grain size on creep of Ti-53.4mol%Al intermetallics at 1100 K

Constant stress creep under compression stress, 100 to 316 MPa, at 1100 K was investigated on single-phase TiAl intermetallics. The material was ingot-cast, isothermally forged, and then annealed to produce stable equi-axed grain structures, whose average grain diameters were 25, 42 and 70m. Creep curves were very similar among the three specimens with different grain diameters and the creep rates at a given strain, as well as the minimum creep rates, depended little on grain size. Two regimes were observed on the stress dependence of the minimum creep rate. The stress exponent under high stresses was about 4.5, independent of grain size. Under stresses lower than about 150 MPa it became about 8.     

Development of a dual‐lamp projector with higher brightness

Stationary projectors mainly used in system applications have recently gained a wider application range, including general presentations in halls and large conference rooms and being used, for example, in digital signage and for monitoring purposes. Consequently, they are required to meet new market demands for durability, reliability, and flexibility in installation in addition to their conventional basic performance such as especially high brightness. To achieve especially high brightness, a new optical system with two lamps is proposed; the profile of the cover glass that prevents the glass from scattering is made aspherical, the profile of the beam‐combining mirror is improved with its position optimized, and the size of the incident plane of the integrator rod is made larger (1.1 times). These measures resulted in an optical system of an even higher efficiency with 7000 lm, which is the highest in its class (according to a June 2010 investigation). Also, the arrangement of two parallel lamps completely eliminated the effect of heat passing from one lamp to the other, which helped secure durability, reliability, and flexibility in installation. Furthermore, the combined use of the unique non‐telecentric optical system, adopted from the conventional single‐lamp model, helps maintain the class‐highest contrast ratio.^1,2     

Path tracking control of Lagrange systems with obstacle avoidance

This paper addresses a path tracking problem with obstacle avoidance for Lagrange systems. The proposed method is based on field potential methods in combination with navigation functions for obstacle avoidance. First, it is shown that a simple combination of the navigation function with the conventional path tracking controller does not work. Therefore, in order to cope with this problem, a new feedback law is proposed for a path parameter which characterizes the reference path. It is proved that the proposed controller achieves both path following and collision avoidance. Moreover, since the method adopts bounded navigation functions, the proposed controllers generate bounded input signals even when target systems approach obstacles. Finally, an experimental evaluation is performed with a two-link manipulator to illustrate the effectiveness of the proposed method.