Analysis of cell survival after multiple fractions per day and low-dose-rate irradiation of two in vitro cultured rat tumor cell lines

Two rat tumor cell lines which differ significantly in radiosensitivity, a rhabdomyosarcoma (R-1) and a ureter carcinoma (RUC-2), were treated with multiple fractions per day and low-dose-rate gamma radiation. The purpose of these experiments was to investigate (i) the influence of fraction size and interfraction interval on repair of sublethal damage (SD) and (ii) whether low-dose-rate irradiation can be simulated by giving multiple fractions per day which might be applied in clinical treatments. In both cell lines, multiple doses were given at 1- to 4-hr intervals. SD repair was at a maximum in 2 hr but did not reach the theoretically expected level. For both cell lines, survival at higher total doses was different from that theoretically expected if repair of SD was assumed to be completed and at the maximum level. To account for the observation that less than complete repair of SD occurred, theoretical survival curves were calculated with the assumption of a constant but less than 100% level of SD repair. Experimental data correlated well with these calculated curves. There were only very small differences in survival after the different multiple fractions per day regimens. Survival after irradiation at a dose rate of 1.00 Gy/hr was found to be similar to that after multiple fractions per day.     

Two year Cottbus reinfarction study with 30 mg aspirin per day.

All 701 heart infarction patients admitted to 15 hospitals in the district of Cottbus between 1981 and 1983 were randomly administered 30, 60 or 1000 mg aspirin daily according to the territorial affiliation of their local hospitals. The physical and drug therapy during the 2 years follow-up was highly standardized; deviations--as far as they occurred--were documented. Lower all-cause mortality was statistically demonstrated in patients over 60 and a lower fatal reinfarction rate in patients over 50 as well as in men. Deaths and fatal reinfarctions were significantly lower among patients with a history of angina pectoris, marked ST-depression, with an infarction location except for the posterior wall and among hypercholesterolemic patients. The preventive effect of 60 mg aspirin daily was less than that of 30 mg in comparison to the 1000 mg group. Side effects were seen in 4 and 8% (first and second year), respectively, of the patients administered 30 mg aspirin as opposed to 22 and 17% in patients allocated 1000 mg. We conclude that the optimum dose of aspirin for preventing reinfarctions could be as low as 30 mg daily.     

Reevaluation of the Cottbus Reinfarction Study with 30 mg aspirin per day 4 years after the end of the study

Four to 6 years after the end of the Cottbus Reinfarction Study with 30, 60 and 1000 mg/day aspirin, the survivors (72% of the patients) were reevaluated under standardized conditions at the district hospital. Nearly all patients (82%) of the former 30 mg group took further on 30 mg aspirin daily whereas of the former 1000 mg group only 20% continued to take doses higher than 500 mg aspirin. Forty-five percent changed to very low doses. Whereas the death rate was nearly the same in all three former dosage groups the total reinfarction rate was higher (22.5%) in the previous 1000 mg group in comparison to the 30 mg group (17.4%, p less than 0.05). The non-fatal reinfarction rate was by 50% lower in the former 30 mg group compared with the previous 1000 mg group. In the age group 50-59 a 8.6% non-fatal reinfarction rate is contrasted to 1.7% reinfarctions in patients of the former 30 mg group (p less than 0.01). The risk factors were not significantly different in the three groups.     

Statistical models for quantifying diagnostic accuracy with multiple lesions per patient

We propose random-effects models to summarize and quantify the accuracy of the diagnosis of multiple lesions on a single image without assuming independence between lesions. The number of false-positive lesions was assumed to be distributed as a Poisson mixture, and the proportion of true-positive lesions was assumed to be distributed as a binomial mixture. We considered univariate and bivariate, both parametric and nonparametric mixture models. We applied our tools to simulated data and data of a study assessing diagnostic accuracy of virtual colonography with computed tomography in 200 patients suspected of having one or more polyps.     

X-ray structure of Galdieria Rubisco complexed with one sulfate ion per active site

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the reactions of carboxylation and oxygenation of ribulose-1,5-bisphosphate. These reactions require that the active site should be closed by a flexible loop (loop 6) of the large subunit. Rubisco from a red alga, Galdieria partita, has the highest specificity for carboxylation reaction among the Rubiscos hitherto reported. The crystal structure of unactivated Galdieria Rubisco has been determined at 2.6 A resolution. The electron density map reveals that a sulfate binds only to the P1 anion-binding site of the active site and the loop 6 is closed. Galdieria Rubisco has a unique hydrogen bond between the main chain oxygen of Val332 on the loop 6 and the epsilon-amino group of Gln386 of the same large subunit. This interaction is likely to be crucial to understanding for stabilizing the loop 6 in the closed state and to making a higher affinity for anionic ligands.     

Development of hyporesponsiveness of natural killer cells to augmentation of activity after multiple treatments with biological response modifiers

Summary Four biological response modifiers (BRMs), MVE-2 (maleic anhydride divinyl ether), Corynebacterium parvum (C. Parvum), PolyICLC (polyinosinic:polycytidylic acid stabilized with poly-l-lysine), and mouse -interferon (-IFN), were tested to assess whether repeated treatments would repeatedly induce or sustain augmented levels of natural killer (NK) cell activity and/or macrophage (M0)-mediated inhibition of tumor cell growth. In contrast to a significant increase in splenic NK activity obtained with a single treatment with each of the agents, multiple treatments with these BRMs led to a progressive decrease in the degree of augmentation of NK activity. In contrast, multiple injections with these agents resulted in sustained augmentation of M0-mediated reactivity. Separation of the spleen cells by Percoll discontinuous density gradient centrifugation indicated that with mice treated once with each BRM high levels of NK activity were detected in the lower density fractions and that these fractions contained a higher percentage of large granular lymphocytes (LGLs) than that found in comparable fractions from normal mice. In contrast, cells in the lower density fractions from mice that received multiple treatments had decreased NK activity and an appreciably lower proportion of LGLs. These results indicate that the development of hyporesponsiveness to augmentation of splenic NK-cell activity following multiple treatments with BRMs may be attributable to a decreased percentage of LGLs, the effector cell population responsible for NK cell-mediated cytotoxicity. Abbreviations used in this paper: BRMs, biological response modifiers; MVE-2, maleic anhydride divinyl ether of molecular weight 15,500; C. parvum, Corynebacterium parvum; PolyICLC, polyinosinic-polycytidylic acid stabilized with poly-l-lysine in carboxymethylcellulose; IFN, interferon; NK cells, natural killer cells; M0, macrophage; LGLs, large granular lymphocytes; PGE, prostaglandin E; FBS, fetal bovine serum; PBS, phosphate-buffer saline composed of 4.86 g NaCl, 0.306 g KH₂PO₄, and 2,417 g NaHPO₄ in 100 ml H₂O adjusted to pH 7.2; LPS, lipopolysaccharide     

Repopulation of intertidal areas with Lessonia nigrescens in northern Chile

Intertidal rocky areas in northern Chile were repopulated experimentally with the brown alga Lessonia nigrescens using spore seeding and placement of reproductive fronds. The results were successful, and it is suggested that methods developed in the field can be done by people without special training.     

Induction of ovulation and multiple ovulation in seasonally-anovulatory mares with equine pituitary fractions

Equine pituitary fractions were used to induce ovulation in seasonally-anovulatory pony mares. Over three experiments, 87% of mares ovulated following twice daily injections for 14 days of equine pituitary fractions. Of the mares which ovulated, 58% had 2 or more ovulations/estrus.     

Gene amplification in murine leukemia cells with multiple drug resistance acquired in vivo

The P388rm and P388rx cell lines resistant to antracycline antibiotics were obtained as a result of chemotherapy of mice bearing P388 leukemia, by means of increasing dosages of rubomycin and ruboxyl, respectively. These cell lines possessed cross-resistance to vinblastine, vincristine, colchicine, actinomycin D and some other drugs. Multidrug resistance (MDR) of P388rm and P388rx is due to decreased uptake of different cytotoxic compounds by the cells. Development of resistance to rubomycin and ruboxyl was accompanied by the appearance of additional chromosomal structures--long homogeneously staining regions (HSRs), double minute chromosomes and others usually containing amplified DNA sequences. Southern blot-hybridization with cloned DNA fragments amplified in Djungarian and Chinese hamster cell lines having MDR has revealed in P388rm and P388rx cells approximately 50-fold amplification of mdr and pC52 genes. Thus, in mouse leukemia cells which acquired MDR in vivo, as a result of chemotherapy, amplification is observed of the same genes that undergo amplification during selection of cell cultures for MDR in vitro.