The influence of the schedule and the dose of gemcitabine on the anti-tumour efficacy in experimental human cancer.

The therapeutic efficacy of gemcitabine, a new nucleoside analogue, was assessed in a variety of well-established human soft tissue sarcoma and ovarian cancer xenografts grown s.c. in nude mice. Tumour lines selected had different histological subtypes, growth rates and sensitivities to conventional cytostatic agents. The three different doses and schedules designed on the basis of a mean weight loss between 5% and 15% were i.p. injections of daily 3.5 mg kg-1 x 4, every 3 days 120 mg kg-1 x 4, and weekly 240 mg kg-1 x 2, which ultimately resulted in 19%, 10% and 4% toxic deaths, respectively. The weekly schedule induced > or = 50% growth inhibition in 2/4 soft tissue sarcoma and 4/6 ovarian cancer lines, while in three ovarian cancer lines > or = 75% growth inhibition was obtained. The anti-tumour effects of gemcitabine appeared to be similar or even better than previous data with conventional drugs tested in the same tumour lines. In comparison with the every 3 days schedule, the weekly and the daily schedule were less effective in 5/7 and 3/3 tumour lines (P < 0.001), respectively. In another experiment in three human tumour lines selected for their differential sensitivity to gemcitabine, weekly injections of 240 mg kg-1 x 6 did not result in a significant increase in the percentages of growth inhibition when compared to lower doses of 120 mg kg-1 or 60 mg kg-1 in the same schedule. However, the 240 mg kg-1 weekly x 6 schedule showed superior effects in 2/3 tumour lines in comparison with the same dose given every 2 weeks x 3 (P < 0.05). The preclinical activity of gemcitabine suggests that the drug can induce responses in soft tissue sarcoma and ovarian cancer patients. Our results further indicate that clinical trials of gemcitabine in solid tumour types should be designed on the basis of a schedule rather than a dose dependence

Non-Collinear Magnetism due to Orbital Degeneracy and Multipolar Interactions

The origin of non-collinear magnetism under quadrupolar ordering is investigated with CeB6 taken as a target system. The mode-mixing effect among 15 multipoles is analyzed based on the Ginzburg-Landau free energy. Then the lower magnetic transition temperature and the order parameters are derived within the mean-field approximation. In the presence of pseudo-dipole-type interactions for the next-nearest neighbors, the observed pattern of non-collinear ordering is indeed stabilized for certain set of interaction parameters. The stability of the phase III' in the magnetic field is also explained, which points to the importance of the next-nearest-neighbor octupole-octupole interaction. Concerning the phase IV in CexLa1-xB6 with x ~ 0.75, a possibility of pure octupole ordering is discussed based on slight modifications of the strength of interactions.Comment: 12 pages, 7 figures, 3 tables, to appear in J. Phys. Soc. Jpn. 70 (6) (2001

Interpocket polarization model for magnetic structures in rare-earth hexaborides

The origin of peculiar magnetic structures in cubic rare-earth (R) hexaborides RB_6 is traced back to their characteristic band structure. The three sphere-like Fermi surfaces induce interpocket polarization of the conduction band as a part of a RKKY-type interaction. It is shown for the free-electron-like model that the interpocket polarization gives rise to a broad maximum in the intersite interaction I(q) around q=(1/4,1/4,1/2) in the Brillouin zone. This maximum is consistent with the superstructure observed in R=Ce, Gd and Dy. The wave-number dependence of I(q) is independently extracted from analysis of the spin-wave spectrum measured for NdB_6. It is found that I(q) obtained from fitting the data has a similarly to that derived by the interpocket polarization model, except that the absolute maximum now occurs at (0,0,1/2) in consistency with the A-type structure. The overall shape of I(q) gives a hint toward understanding an incommensurate structure in PrB_6 as well.Comment: 5 pages, 3 figures, submitted to J.Phys.Soc.Jp

Functional coupling of glycolysis and phosphocreatine utilization in anoxic fish muscle: an in vivo 31P NMR study

Animal science

Accommodation and vergence response gains to different near cues characterize specific esotropias

Aim. To describe preliminary findings of how the profile of the use of blur, disparity and proximal cues varies between non-strabismic groups and those with different types of esotropia. Design. Case control study Methodology. A remote haploscopic photorefractor measured simultaneous convergence and accommodation to a range of targets containing all combinations of binocular disparity, blur and proximal (looming) cues. 13 constant esotropes, 16 fully accommodative esotropes, and 8 convergence excess esotropes were compared with age and refractive error matched controls, and 27 young adult emmetropic controls. All wore full refractive correction if not emmetropic. Response AC/A and CA/C ratios were also assessed. Results. Cue use differed between the groups. Even esotropes with constant suppression and no binocular vision (BV) responded to disparity in cues. The constant esotropes with weak BV showed trends for more stable responses and better vergence and accommodation than those without any BV. The accommodative esotropes made less use of disparity cues to drive accommodation (p=0.04) and more use of blur to drive vergence (p=0.008) than controls. All esotropic groups failed to show the strong bias for better responses to disparity cues found in the controls, with convergence excess esotropes favoring blur cues. AC/A and CA/C ratios existed in an inverse relationship in the different groups. Accommodative lag of >1.0D at 33cm was common (46%) in the pooled esotropia groups compared with 11% in typical children (p=0.05). Conclusion. Esotropic children use near cues differently from matched non-esotropic children in ways characteristic to their deviations. Relatively higher weighting for blur cues was found in accommodative esotropia compared to matched controls

Bacteriochlorophyll/imidazole and chlorophyll/imidazole complexes are negatively charged in an apolar environment

Bio-organic Synthesi

Multipolar Interactions in the Anderson Lattice with Orbital Degeneracy

Microscopic investigation is performed for intersite multipolar interactions in the orbitally degenerate Anderson lattice, with CeB$_6$ taken as an exemplary target. In addition to the $f^0$ intermediate state, $f^2$ Hund's-rule ground states are included as intermediate states for the interactions. The conduction-band states are taken as plane waves and the hybridization as spherically symmetric. The spatial dependences of multipolar interactions are given by the relative weight of partial wave components along the pair of sites. It is clarified how the the anisotropy arises in the interactions depending on the orbital degeneracy and the spatial configuration. The stability of the $\Gamma_5$ antiferro-quadrupole order in the phase II of CeB$_6$ is consistent with our model. Moreover, the pseudo-dipole interactions follow a tendency required by the phenomenological model for the phase III.Comment: 30 pages, 4 figure