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The mechanisms of action of a novel macromolecular antitumor antibiotic (SN-07) were examined using cultured mouse lymphoid leukemia L1210 cells. A shoulder exponential-type cytotoxicity was observed when the cells were treated with 3.13 to 100 ng/ml SN-07 for 1 hr and surviving colonies were counted after a 14-day incubation. It was found that 500 ng/ml SN-07 inhibited both RNA and DNA syntheses significantly at 40 and 80 min, respectively, while 8,000 ng/ml did not affect protein synthesis at 80 min. Treatment with a low concentration (80 ng/ml) of SN-07 for 1 hr inhibited both RNA and DNA syntheses after a 24-hr post-incubation. The alkaline elution technique revealed that 8,000 ng/ml SN-07 induced DNA interstrand cross-links time-dependently for 1 to 4 hr, and a 1-hr treatment with 80 to 8,000 ng/ml SN-07 induced DNA breaks after a 24-hr post-incubation. According to flow cytometric analysis, most L1210 cells progressed to the G2 phase in the cell cycle at a cytostatic concentration (25 ng/ml) of SN-07, and typical inhibition of the cell cycle progression was observed at a cytocidal concentration (200 ng/ml).

Although CDDP has been widely used for cancer chemotherapy in recent years, the problem is that it causes a renal dysfunction as a side effect. As briefly reported here, we have currently used this drug for the treatment of stomach esophageal cancers as a part of multidepartmental therapy, and obtained a finding on the therapeutic usefulness, particularly for monitoring the renal function before and after administration. The subjects were 6 patients with stomach and 11 with esophageal cancer given CDDP at the dose of 50 mg 2 courses, in principle, a single course per week. Blood transfusion was carried out in an amount of 1,000 ml before administration, 2,500 ml on the day of treatment and 1,000 ml for 3 days after administration. When the effects of CDDP on urinary BUN, Na, K, Cl, Mg, NAG, beta 2 microglobulin, Ccr and FENa levels were measured for the determination of renal functions before and after administration, NAG and beta 2 microglobulin levels were conceivably found to be useful indices.

Retinal functional imaging of patients with typical and atypical retinal pigmentary dystrophies was investigated by three dimensional (XY plane and time) analysis of ERG topography by comparing visual field and fluorescein angiographic findings. The three dimensional analysis revealed that the area of maximal amplitude deviated to the skin area closest to the dominant location of the retinal pigmentary dystrophy (the so-called paradoxical localization). In patients with temporoinferior sectorial retinal pigmentary dystrophy, for example, the maximal amplitude of the a-, b-waves and retinal oscillatory potentials deviated toward the temporoinferior side on the surface topography. These characteristic phenomena of a- and b-waves were found in 60.8% of all patients. Flicker topography with a stimulus frequency of 30 Hz was especially successful in showing the existence and location of paramacular involvement of retinal dystrophy within the area surrounding temporal vascular arcades. The detectability of macular asymmetric involvement was 65.2%. No significant topographic changes were detected in cases in the early stage with no remarkable visual field defects, or in the end stage with remarkable concentric field defects and complicated glaucomatous visual field defects. A comparative study of topographic changes, visual field changes and fluorescein angiographic findings showed that topographic changes in the a-, b-waves, retinal oscillatory potentials and 30Hz flicker components coincided more closely with visual field changes than fluorescein angiographic findings. We proposed that retinal pigmentary dystrophy is not a homogeneous lesion in its progression and believe that the ERG topography method can, by the imaging of dominant locations, detect this disease as well as visual field testing.

Retinal functional imaging in patients with rhegmatogenous retinal detachment and related pathological conditions was investigated by three dimensional analysis of ERG topography. The three dimensional analysis revealed that the area of maximal amplitude deviated to the skin area closest to the location of the retinal detachment (paradoxical localization). In temporal retinal detachment, for example, the maximal amplitude of the a- and b-waves deviated toward the temporal side on the surface topography. The depth of the retinal detachment was clearly indicated by differential ERG topography. Flicker ERG with a stimulus frequency of 30Hz was especially successful in showing the existence and location of macular detachment within the area surrounding the temporal vascular arcades. ERG topography also indicated the meridional extent of retinal detachment. When there was detachment in two quadrants (e.g., two inferior quadrants), deviation in the surface topography of a- and b-waves appeared in the same quadrants. When detachment expanded into three quadrants, deviation of the amplitude of a- and b-waves closely resembled the extent of the detachment. In addition, however, there was inverse a- and b-wave surface topography on the opposite skin area. When there were two quadrants of retinal detachment, there were two quadrants of inverse a-and b-waves. When there were three quadrants of retinal detachment, there was only one quadrant of inverse a- and b-waves. No inverse a- and b-waves were detected when there was only one quadrant of retinal detachment. In such cases, however, deviation in the surface topography covered three quadrants. These abnormalities were detected in 90.6% of all cases with the retinal detachment disappeared after the retina was reattached. While the buckling procedure and argon laser retinopexy had little effect on the topographical distribution, it was markedly distorted by cryoretinopexy. No remarkable changes in the topographical distribution of a- and b-waves were detected in pathological conditions related to rhegmatogenous retinal detachment. This new method for functional imaging of the retina should be valuable for objective clinical evaluation of retinal detachment.

A new artificial blood substitute, FOB, which has been shown to be a good solvent for oxygen, contains a Bromine atom within its molecule. FOB is taken up in tumor macrophages and the Bromine shows opacity on X-ray film by absorbance of X-rays. In this study, tumor imaging possibilities were studied using conventional roentgenograms, on mice bearing transplanted Ehrlich ascites tumors on the right leg and which were given a 1-ml injection of 50 w/v % FOB. The results obtained follows: Solid Ehrlich tumors were imaged clearly wih injected FOB. X-ray films showed persisting homogeneous tumor staining, and irregular linear and plaque opacities. Larger tumors (more than 5,000 mm3 in volume) were imaged less clearly than smaller ones (about 1,000 mm3 in volume), because of superimposition of X-ray absorbance of the FOB taken up and of the larger tumor mass itself. The patterns of FOB taken up into the transplanted tumor were different according to various tumor growth time. Tumor imaging effect was enhanced by double time injection of 1 ml FOB. Histological features of Ehrlich tumors injected with FOB showed that FOB was phagocytosed by macrophages in the tumor tissue. The radiosensitization effect of FOB has already been reported by us. These results suggested that FOB acts not only as a sensitizer in radiation therapy, but also as a tumor imaging agent for diagnosis of the localization of malignancy in radiotherapeutic planning.

A newly isolated strain of Streptomyces sp. produces a new nucleoside antibiotic, ascamycin and the corresponding dealanyl derivative. The structure of ascamycin was determined to be 2-chloro-9-beta-[5-O-(N-L-alanyl)sulfamoyl-D-ribofuranosyl]-adenine. Remarkable selective toxicity of ascamycin compared to the dealanyl derivative was accounted for on the basis of a dealanylating enzyme present in the envelope of sensitive bacteria. After dealanylation, it becomes permeable to cell membrane.

The time course of the concentration of cefmetazole (CMZ) in the serum and in skin and intestinal tissues was determined after a single intravenous injection of 2 g of the drug. CMZ moved into them well. Furthermore, 41 patients with postoperative wound infection (superficial in 29 and deep in 12) were treated with CMZ 2-4 g daily. Bacteriological examination of the lesions with simultaneously carried out. As a result, 101 strains of bacteria were isolated and identified. Mixed infection was found in 27 cases (65.9%). Fifteen strains (14.9%) of E. coli, 15 (14.9%) of B. fragilis, 7 (6.9%) of Klebsiella sp. and 7 (6.9%) of Proteus sp., were the main bacteria isolated. Eight cases (19.5%) had mixed infection of E. coli and B. fragilis. The committee (3 members) evaluated CMZ to be effective in 75.6% (31 of 41 cases) and bacteria disappeared in 60.5% (23 of 38 cases). The side effects observed were pyrosis and feeling of gastric malaise in 1 case. The results suggest that CMZ is useful, which exerts an excellent effect on postoperative wound infections.

Experiments were designed to investigate the importance of the endothelium in the relaxation of isolated rat aorta caused by a beta adrenoceptor agonist. Mechanical removal of the endothelium attenuated the relaxation induced by isoproterenol (ISO) and did not affect the relaxation produced by forskolin and by sodium nitroprusside. High concentrations of ISO produced an increase in the resting tension of aortic strips with and without endothelium in a concentration-dependent manner. Mechanical removal of the endothelium or treatment with methylene blue enhanced the maximal contraction induced by ISO. Phentolamine antagonized the contractile responses induced by ISO. In the case of streptozotocin-induced diabetic rats, both aortic strips with and without endothelium generated concentration-response curves for ISO-induced relaxation that were shifted to the right. The relaxant responses to forskolin and sodium nitroprusside were not significantly different between vessels from diabetic and age-matched control rats. In both aortic strips with and without endothelium, the maximal contraction in response to high concentrations of ISO was significantly enhanced in strips from diabetic rats. These results suggest that ISO-induced relaxation of aortic strips with endothelium is mediated by beta adrenoceptors on both the endothelium and the smooth muscle, and high concentrations of ISO produce an increase in the resting tension through alpha adrenoceptors. It is further suggested that the decreased relaxant response of the aorta to ISO in diabetes may be due to decreased density or affinity of beta adrenoceptors on the smooth muscle.

Perfluorochemical emulsion can dissolve large amount of oxygen, carry it into tissues, and consequently enhance the response of hypoxic tumor cells to radiation. Previously we reported on the radiosensitizing effect of perfluorochemical emulsion. In the present study, the minimal effective dose of Fluosol-DA Saline 20% (FDAS), one of preparations of perfluorochemical emulsion, was determined. Mice bearing Lewis lung carcinoma in their thighs were injected in single i.v. of FDAS (1.25-20 ml/kg) and were allowed to breath carbogen (95% O2 + 5% CO2) for 30 min. before and during irradiation (15 Gy). The effect of FDAS was measured by the growth delay of the treated tumor. Administration of FDAS at over 5 ml/kg together with carbogen breathing significantly (p less than 0.01) enhanced the tumor growth delay as compared with treatment of carbogen breathing without FDAS. There was a significant difference (p less than 0.05) in the radiosensitizing effect between injection of FDAS at 5 ml/kg and 20 ml/kg, while there were not significant differences between injection of FDAS at 5 ml/kg and 10 ml/kg, or 10 ml/kg and 20 ml/kg, respectively. These results indicate that the minimal effective dose of FDAS is 5 ml/kg, which could be applied to clinical fractionated irradiation therapy as a standard FDAS-dose.

To enhance tissue PO2 of radioresistant hypoxic cells of tumor, artificial blood substitute (FOB) was applied, because it is excellent solvent for oxygen and allows the blood circulation system to recover and consequently increase the oxygen supply from blood to the tissue. When trasplanted Ehrlich tumor of mice on thigh grew about 1,000 mm3 in volume, those were divided into three groups, group 1: 60Co gamma-ray irradiation alone, group 2: irradiation under breathing oxygen, and group 3: irradiation under breathing oxygen after exchange transfusion with FOB. The radiosensitization of FOB was studied by comparing with the OER values of three groups for 50% TGD time, 50% SD time, and 50% and 75% TCP. The OER values of 50% TGD time, 5, 10 and 50% SD time 10 of oxygen group were 1.46, 1.29, and 1.22, respectively, and oxygen effect was observed in this group. Those values of FOB group were 2.02, 1.56, and 1.56, respectively and oxygen effect of FOB group was greater than those of oxygen effect of FOB group was greater than those of oxygen group. Animals receiving FOB were apparently radiosensitized by oxygen against animals breathing oxygen at small doses irradiation effect (50% TGD time, and 50% SD time). The OER values of 50% and 75% TCP at 30 days and 90 days after irradiation of oxygen group were about 1.5 (1.46-1.61) and these of FOB group about 1.3 (1.15-1.38). Radiosensitization by oxygen of animals receiving FOB was not clearly recognized against animals breathing oxygen in TCP effect at high dose irradiation. These results indicate that radioresistant hypoxic cells of tumor receiving artificial blood substitute (FOB) increase the sensitivity of 60Co gamma-ray irradiation, especially at small dose irradiation.

Cadmium‐tin oxide (CTO) films with high conductivity and high transparency were prepared by rf sputtering from a CdO‐SnO2 target in an Ar or Ar‐O2 atmosphere. The resistivity of CTO films was 6.5×10−4 Ω in the film thickness range of 2500–15000 A, and the average transmission was 90% over the visible region.

Thermal expansivity and magnetostriction of an EuO single crystal were determined by using the strain gauge method in the temperature ranges 20° to 250°K and 4.2° to 150°K, respectively, and in magnetic fields up to 20 kOe. The magnetoelastic component of expansivity αme is observed to be proportional to the magnetic specific heat Cm.1 As a result we obtain a temperature independent ``magnetic'' Gruneisen constant ∂ ln Um/∂ ln V=[minus]5.3 given by −3αmeCm−1BT using BT (isothermal bulk modulus) =1.07×1012 dyn/cm2. For Um, the internal magnetic energy, we derive also the variation with temperature and magnetic field Um(T, H)/Um(0), the variation with pressure ∂ ln Um/∂ P=4.9×10−12 dyn−1cm2, and the value Um(0) = −4.9×108 erg·cm−3 at 0°K. These results are obtained from treating various combinations of measurables including magnetization, isotropic forced magnetostriction, and zero‐temperature volume anomaly as well as αme and Cm. The manner of suppression of the λ‐transition by a magnetic field is also rev...

Evidence has been presented; The degree of fat droplets was changed liver discases and fatty metamorphosis was correlated with some liver function tests