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.     

A far-infrared spectroscopic study of low temperature soft phonon mode in Tris-Sarcosine Calcium Chloride(TSCC)

Temperature dependences of the soft phonon frequency and the damping constant in Tris-Sarcosine Calcium Chloride (TSCC) single crystal have been investigated between 5K and 100K by using a Fourier-transform far-infrared spectrometer. It has been observed that the soft phonon frequency decreases gradually and the damping constant increases as the transition temperature is approached from below The damping constant varies from 7cm^-1 a 90K to less than 0.5cm^-1 at 5K. It has been found that the damping constant is approximately proportional to temperature below about 60K.     

An empirical approach for structure-based prediction of carbohydrate-binding sites on proteins

A computer program system was developed to predict carbohydrate-bindingsites on three-dimensional (3D) protein structures. The programssearch for binding sites by referring to the empirical rulesderived from the known 3D structures of carbohydrate–proteincomplexes. A total of 80 non-redundant carbohydrate–proteincomplex structures were selected from the Protein Data Bankfor the empirical rule construction. The performance of theprediction system was tested on 50 known complex structuresto determine whether the system could detect the known bindingsites. The known monosaccharide-binding sites were detectedamong the best three predictions in 59% of the cases, whichcovered 69% of the polysaccharide-binding sites in the targetproteins, when the performance was evaluated by the overlapbetween residue patches of predicted and known binding sites. Received April 24, 2003; revised June 2, 2003; accepted June 10, 2003.     

Nonlinear repetitive control with application to trajectory control of manipulators

In this article, a new control scheme named repetitive control is proposed for a class of nonlinear systems described by x(t) = Ax(t) + Bu(t) + n(x(t)) and y(t) = Cx(t), in which the controlled variables follow periodic reference commands. The stability condition is derived by applying the passivity theorem. We show how to apply the repetitive control scheme to the trajectory control of a manipulator. A simple repetitive control scheme is developed for the trajectory control of a manipulator by using nonlinear compensation and feedbacks of position and velocity signals. Experimental results for a three link manipulator verify that the proposed repetitive control reduces the tracking error to a very low level.     

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.     

Titania NOx sensors for exhaust monitoring

Oxide semiconductors have been examined to develop NO_x sensors for exhaust monitoring. Titania doped with trivalent elements, such as Al³⁺, Sc³⁺, Ga³⁺ or In³⁺, has a good sensitivity and selectivity to NO between 450 and 550 °C, and shows rapid response. A sensor probe for monitoring exhaust NO_x has been fabricated. Many kinds of interference gases, such as C₃H₆, CO and SO₂, have been found to have only a slight influence on the sensor response to NO. The influence of O₂ and H₂O is also negligible, except for the cases of 0% H₂O and fuel-rich conditions. In accordance with these results, the sensor probe operates satisfactority in the exhaust gas of various combustion conditions without interference from the various kinds of gas species in the exhaust gases.     

Numerical investigation of zoomable holographic projection without a zoom lens

Holographic projection is for laser displays and has the merits of being aberration free, producing high‐contrast images, having the ability of color reconstruction with one spatial light modulator, and so on. In this paper, we propose a zoomable holographic projection without using a zoom lens and verify the proposed method by using numerical simulation. Although such a system can be readily realized to use the features of holography, which is capable of recording a large image exceeding the hologram size, the required calculation is very time consuming. For acceleration, we used shifted Fresnel diffraction for setting different sampling rates on a hologram and projected image. The proposed method can project any zoom‐in and zoom‐out image between zeroth‐order and first‐order lights, and the processing time and required memory for the zoom are constant.