Sequential administration of interferon γ and interleukin-2 in metastatic renal cell carcinoma: results of a phase II trial

Background: Because of the known efficacy of several cytokines in the treatment of advanced renal cell cancer (RCC), we have conducted a phase II trial of the efficacy and toxicity of subcutaneous interferon γ (IFNγ) and interleukin-2 (IL-2). Methods: 63 patients with progressive metastatic RCC were treated with 100 μg recombinant IFNγ1b administered three times weekly during weeks 1 and 2 and with 4.5 MU recombinant IL-2 administered on 4 consecutive days during weeks 3 and 4, every 6 weeks. Results: 11% of patients had an objective response (CR: 3%, PR: 8%), 33% had SD. Toxicity was generally mild. The median duration of remissions (CR + PR) was 9.6 months; the median duration of SD 8 months. A significant survival benefit was evident at a median observation time of 51 months for patients (44%) responding to therapy (P < 0.0001). Conclusions: we conclude that sequential treatment with IFNγ and IL-2 may prolong survival in patients with metastatic RCC responding to therapy. Received: 2 April 2000 / Accepted: 21 April 2000     

Distribution and abundance of the salmonid parasite Parvicapsula minibicornis (Myxozoa) in the Klamath River basin (Oregon-California, U.S.A.)

The distribution and abundance of the myxosporean parasite Parvicapsula minibicornis in the Klamath River mirrored that of Ceratomyxa shasta, with which it shares both its vertebrate and invertebrate host. Assay of fish held at sentinel sites and water samples collected from those sites showed that parasite prevalence was highest below Iron Gate dam, which is the barrier to anadromous salmon passage. Above this barrier parasite levels fluctuated, with the parasite detected in the free-flowing river reaches between reservoirs. This was consistent with infection prevalence in the polychaete host, Manayunkia speciosa, which was greater than 1% only in populations tested below Iron Gate dam. Although a low prevalence of infection was detected in juvenile out-migrant fish in the Trinity River, the tributaries tested did not appear to be a significant source of the parasite to the mainstem despite the presence of large numbers of infected adult salmon that migrate and spawn there. Rainbow trout became infected during sentinel exposure, which expands the host range for P. minibicornis and suggests that wild rainbow trout populations are a reservoir for infection, especially above Iron Gate dam. High parasite prevalence in the lower Klamath River is likely a combined effect of high spore input from heavily infected, spawned adult salmon and the proximity to dense populations of polychaetes.     

Differential behavioral responses by reproductive and non-reproductive male round gobies (Neogobius melanostomus) to the putative pheromone estrone

Previous studies have shown that the frequency of gill ventilation during exposure to estrone and gonadal extracts in the round goby (Neogobius melanostomus) is linked to olfactory sensory input. Control over gill ventilation may be a regulatory mechanism used for odorant sampling during reproductive periods. In this study, we examined changes in gill ventilation in osmic and anosmic (nasal occluded), reproductive and non-reproductive male round gobies to a putative steroidal pheromone estrone (1,3,5(10)-estratrien-3-ol-17-one). We tested 5 different concentrations of estrone (10(-12) to 10(-8) M) and showed that the response threshold for estrone varied with the male's reproductive status; it was 10(-11) M in reproductive males, and rose to 10(-9) M in non-reproductive males. However, anosmic reproductive and non-reproductive males did not respond to estrone. These findings suggest that olfactory responses to putative pheromones may change depending on the reproductive status of the fish.     

Effect of Cation Composition on the Mechanical Stability of Perovskite Solar Cells

Photoactive perovskite semiconductors are highly tunable, with numerous inorganic and organic cations readily incorporated to modify optoelectronic properties. However, despite the importance of device reliability and long service lifetimes, the effects of various cations on the mechanical properties of perovskites are largely overlooked. In this study, the cohesion energy of perovskites containing various cation combinations of methylammonium, formamidinium, cesium, butylammonium, and 5‐aminovaleric acid is reported. A trade‐off is observed between the mechanical integrity and the efficiency of perovskite devices. High efficiency devices exhibit decreased cohesion, which is attributed to reduced grain sizes with the inclusion of additional cations and PbI₂ additives. Microindentation hardness testing is performed to estimate the fracture toughness of single‐crystal perovskite, and the results indicated perovskites are inherently fragile, even in the absence of grain boundaries and defects. The devices found to have the highest fracture energies are perovskites infiltrated into a porous TiO₂/ZrO₂/C triple layer, which provide extrinsic reinforcement and shielding for enhanced mechanical and chemical stability.     

Infilled Ditches are Hotspots of Landscape Methane Flux Following Peatland Re-wetting

Peatlands are large terrestrial stores of carbon, and sustained CO₂ sinks, but over the last century large areas have been drained for agriculture and forestry, potentially converting them into net carbon sources. More recently, some peatlands have been re-wetted by blocking drainage ditches, with the aims of enhancing biodiversity, mitigating flooding, and promoting carbon storage. One potential detrimental consequence of peatland re-wetting is an increase in methane (CH₄) emissions, offsetting the benefits of increased CO₂ sequestration. We examined differences in CH₄ emissions between an area of ditch-drained blanket bog, and an adjacent area where drainage ditches were recently infilled. Results showed that Eriophorum vaginatum colonization led to a “hotspot” of CH₄ emissions from the infilled ditches themselves, with smaller increases in CH₄ from other re-wetted areas. Extrapolated to the area of blanket bog surrounding the study site, we estimated that CH₄ emissions were around 60 kg CH₄ ha^?1 y^?1 prior to drainage, reducing to 44 kg CH₄ ha^?1 y^?1 after drainage. We calculated that fully re-wetting this area would initially increase emissions to a peak of around 120 kg CH₄ ha^?1 y^?1, with around two-thirds of the increase (and 90% of the increase over pre-drainage conditions) attributable to CH₄ emissions from E. vaginatum-colonized infilled ditches, despite these areas only occupying 7% of the landscape. We predicted that emissions should eventually decline toward pre-drainage values as the ecosystem recovers, but only if Sphagnum mosses displace E. vaginatum from the infilled ditches. These results have implications for peatland management for climate change mitigation, suggesting that restoration methods should aim, if possible, to avoid the colonization of infilled ditches by aerenchymatous species such as E. vaginatum, and to encourage Sphagnum establishment.     

Expression of thymidine phosphorylase in peripheral blood cells of breast cancer patients is not increased by paclitaxel

Background  

A synergistic cytotoxic effect has been hypothesized for taxanes and capecitabine, a prodrug of 5-fluorouracil. Based on preclinical studies, this synergism has been attributed to an up-regulation of the enzyme thymidine phosphorylase (TP). Beside tumour tissue, TP is highly expressed in white blood cells, possibly causing increased hematotoxicity, when taxanes are combined with capecitabine. So far, this hypothesis has not been investigated in humans.