Tumor regression in cancer patients by very low doses of a T cell-engaging antibody     

Bargou R  Leo E  Zugmaier G  Klinger M  Goebeler M  Knop S  Noppeney R  Viardot A  Hess G  Schuler M  Einsele H  Brandl C  Wolf A  Kirchinger P  Klappers P  Schmidt M  Riethmüller G  Reinhardt C  Baeuerle PA  Kufer P 《Science (New York, N.Y.)》2008,321(5891):974-977

Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non-Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell-engaging antibodies appear to have therapeutic potential for the treatment of malignant diseases.  相似文献   

The enigma of prokaryotic life in deep hypersaline anoxic basins     

van der Wielen PW  Bolhuis H  Borin S  Daffonchio D  Corselli C  Giuliano L  D'Auria G  de Lange GJ  Huebner A  Varnavas SP  Thomson J  Tamburini C  Marty D  McGenity TJ  Timmis KN;BioDeep Scientific Party 《Science (New York, N.Y.)》2005,307(5706):121-123

Deep hypersaline anoxic basins in the Mediterranean Sea are a legacy of dissolution of ancient subterranean salt deposits from the Miocene period. Our study revealed that these hypersaline basins are not biogeochemical dead ends, but support in situ sulfate reduction, methanogenesis, and heterotrophic activity. A wide diversity of prokaryotes was observed, including a new, abundant, deeply branching order within the Euryarchaeota. Furthermore, we demonstrated the presence of a unique, metabolically active microbial community in the Discovery basin, which is one of the most extreme terrestrial saline environments known, as it is almost saturated with MgCl2 (5 M).  相似文献   

Building and destroying social capital: The case of cooperative movements in Denmark and Poland     

Jarka Chloupkova  Gunnar Lind Haase Svendsen  Gert Tinggaard Svendsen 《Agriculture and Human Values》2003,20(3):241-252

Social capital, measured as the level of trustamong people, may be regarded as a newproduction factor alongside the traditionalones of human and physical capital. Withappropriate levels of social capital,monitoring and transaction costs can be savedand thus economic growth stimulated. Vialinking social capital to rural development andcomparing the cases of agricultural cooperativemovements in Denmark and Poland, this paperidentifies possible roots of building socialcapital and suggests that social capital wasbuilt through a lengthy process in bothcountries during the 19th century. However,the comparison of the present level of socialcapital indicates that the level of socialcapital is significantly higher in Denmark thanin Poland. The paper concludes that the reasonfor this difference is the fact that theoriginal accumulation of social capital inPoland was destroyed by the communist regime.  相似文献   

Resistance in spelt wheat to yellow rust     

Gert H. J. Kema 《Euphytica》1992,63(3):207-217

Summary Seven spelt wheat accessions of different origin were hybridized with the susceptible bread wheat cultivar Taichung 29 in order to study the genetics of their resistance to yellow rust (Puccinia striiformis Westend. f. sp. tritici). One Iranian and five European accessions were found to carry Yr5 of Triticum aestivum ssp. spelta var. album, whereas a factor for resistance in the Iranian accession 415 was confirmed to be genetically distinct from Yr5. The alleles for resistance in each of the accessions studied showed a monogenic dominant mode of inheritance. Twenty-eight spelt wheat accessions, including those studied for their resistance to yellow rust, were subjected to polyacrylamide-gel-electrophoresis to study variation for gliadin storage protein patterns. Thirteen distinct patterns were revealed, implying the presence of duplicates within the studied spelt wheat collection.  相似文献   

Quantitative analysis of transmission parameters for bluetongue virus serotype 8 in Western Europe in 2006     

de Koeijer AA  Boender GJ  Nodelijk G  Staubach C  Meroc E  Elbers AR 《Veterinary research》2011,42(1):53

ABSTRACT: The recent bluetongue virus serotype 8 (BTV-8) epidemic in Western Europe struck hard. Controlling the infection was difficult and a good and safe vaccine was not available until the spring of 2008. Little was known regarding BTV transmission in Western Europe or the efficacy of control measures. Quantitative details on transmission are essential to assess the potential and efficacy of such measures.To quantify virus transmission between herds, a temporal and a spatio-temporal analysis were applied to data on reported infected herds in 2006. We calculated the basic reproduction number between herds (Rh: expected number of new infections, generated by one initial infected herd in a susceptible environment). It was found to be of the same order of magnitude as that of an infection with Foot and Mouth Disease (FMD) in The Netherlands, e.g. around 4. We concluded that an average day temperature of at least 15°C is required for BTV-8 transmission between herds in Western Europe. A few degrees increase in temperature is found to lead to a major increase in BTV-8 transmission.We also found that the applied disease control (spatial zones based on 20 km radius restricting animal transport to outside regions) led to a spatial transmission pattern of BTV-8, with 85% of transmission restricted to a 20 km range. This 20 km equals the scale of the protection zones. We concluded that free animal movement led to substantial faster spread of the BTV-8 epidemic over space as compared to a situation with animal movement restrictions.  相似文献   

Invertebrates Minimize Accumulation of Metals and Metalloids in Contaminated Environments     

Joerg Schaller  Carsten Brackhage  E. Gert Dudel 《Water, air, and soil pollution》2011,218(1-4):227-233

Many studies were conducted measuring the lethal concentration of pollutants by using a contaminated solution or polluted sediments. Considering the impact of polluted food on mortality and uptake quantity of invertebrate shredders in batch cultures, little is known about, e.g. uranium and cadmium. Consequently, we investigated in situ the impact of metal and metalloid polluted food and water on Gammarus pulex L. under nature-like conditions. In contrast to other publications, a very low mortality rate of the invertebrates was found. Furthermore, fixation of elements by G. pulex was shown to be low compared to initial concentrations. Fixation of non essential metals and metalloids is shown to take place mainly on the surface of the invertebrates. This is deduced from easy desorption of a relevant amount of fixed metals and metalloids. It is concluded that the accumulation of metals and metalloids in situ under nature-like conditions within the food web via invertebrate shredders is very low. The invertebrates seem to minimize the uptake of non essential elements in the presence of nutrient-rich food even in habitats with higher contamination levels. Hence, invertebrates seem to be adapted to higher contamination levels in their favourable habitats.  相似文献   

Uptake,distribution and excretion of magnesium inOreochromis mossambicus: dependence on magnesium in diet and water     

Marcel J. C. Bijvelds  Gert Flik  Zvonimir I. Kolar  Sjoerd E. Wendelaar Bonga 《Fish physiology and biochemistry》1996,15(4):287-298

The euryhaline Mozambique tilapia (Oreochromis mossambicus) shows a more marked ability to adapt to low magnesium levels in food and water than many other fish species. Nonetheless, the internal distribution of magnesium is altered under low-magnesium conditions. The amount of magnesium in scales, and to a lesser extent the vertebral bone, is reduced and hence serve as magnesium reservoirs. The magnesium concentration of muscle is only marginally reduced by low external magnesium, suggesting that magnesium is partitioned to ensure normal muscle functioning. The water magnesium is of vital importance, as exposure to low-magnesium water markedly deminished the ability of tilapia to adapt to low-magnesium feeding. However, magnesium intake from the water, eithervia the integument or drinking, does not increase in lowmagnesium fed fish, despite an increased opercular chloride cell density. The growth related magnesium accumulation of tilapia under low-magnesium conditions approximates the total intake of the element (from the food and from the water), indicating that magnesium losses are minimized and that the magnesium absorption from the gastrointestinal tract may be highly efficient and very important.  相似文献   

Sodium dependent ion transporters in trout gills     

G. Flik  T. Kaneko  A.M. Greco  J. Li  J.C. Fenwick 《Fish physiology and biochemistry》1997,17(1-6):385-396

Biochemical procedures developed to isolate plasma membranes from the branchial epithelium of rainbow trout (Oncorhynchus mykiss) yield membrane fractions that are specifically enriched in the plasma membrane marker enzyme Na⁺/K⁺-ATPase. As the bulk of the branchial Na⁺/K⁺-ATPase is assumed to be confined to the mitochondria-rich chloride cells, such membrane preparations must contain the essence of the enzymatic machinery of the chloride cells. Basal Na⁺ activity in branchial (chloride) cells is around 10 millimolar and, accordingly, we find a K_m for Na⁺ of the Na⁺/K⁺-ATPase of 13 millimolar, indicating that the enzyme may be regulated by changes in cytosolic sodium. The Na⁺-gradient across the serosal plasma membrane created by this pump provides energy for 3Na⁺/Ca²⁺-exchange and bumetanide-sensitive Na⁺/K⁺/2Cl^--cotransport. Here we further postulate the presence of a Na⁺/Cl^--cotransporter, indicated by thiazide-sensitive, bumetanide-insensitive transport of Na⁺ and Cl^-; this cotransporter activity awaits the characterization of its kinetics. The Na⁺/Ca²⁺-exchanger has kinetic characteristics compatible with a regulatory role of cytosolic Na⁺ in the activity of this carrier. Both Na⁺/Ca²⁺-exchange and Ca²⁺-ATPase activity may contribute to transport of Ca²⁺, the former having lower affinity for calcium but a higher capacity than the latter carrier. The Na⁺/K⁺/2Cl^--cotransporter has kinetics that favor a regulatory role for plasma K⁺ in the activity of this carrier. Seawater adaptation leads to increased activity of cotransporter molecules in the plasma membrane fractions (the activity increases relative to that of the Na⁺/K⁺-ATPase) and this may reflect a function in Cl^--extrusion performed by the chloride cells in a seawater environment. A function for the cotransporter in the gills of freshwater fish may be the regulation of cell volume.  相似文献   

Survey for viruses affecting maize along the major grain transport route between Gauteng and KwaZulu-Natal in South Africa     

Nel  Natalie  Pietersen  Gert  Read  David Alan  Pietersen  Gerhard 《European journal of plant pathology / European Foundation for Plant Pathology》2021,160(3):623-635

European Journal of Plant Pathology - The recent introduction of maize chlorotic mottle virus (MCMV) and spread of the resulting maize lethal necrosis disease (MLN) in East Africa presents a threat...  相似文献   

Triazole fungicides and the selection of resistance to medical triazoles in the opportunistic mould Aspergillus fumigatus     

Paul E Verweij  Gert HJ Kema  Bas Zwaan  Willem JG Melchers 《Pest management science》2013,69(2):165-170

Azole resistance is an emerging problem in the opportunistic mould Aspergillus fumigatus. The triazoles are the most important agents for the management of Aspergillus diseases in humans. Selection for acquired resistance may occur in the hospital setting through exposure to high doses of azoles during azole therapy, but evidence is accumulating that A. fumigatus may become resistant to medical triazoles through environmental exposure to fungicides. The recovery of A. fumigatus isolates resistant to the medical triazoles from azole‐naive patients as well as from the environment strongly indicates an environmental route of resistance selection. Molecule alignment studies have identified five fungicides that share a very similar molecule structure with the medical triazoles, and thus may have selected for mechanisms that confer resistance to both groups of compounds. It is important to explore further the presumed fungicide‐driven route of resistance selection in order to implement effective preventive measures as the prevalence of azole resistance in A. fumigatus continues to increase and causes major challenges in the management of azole‐resistant Aspergillus diseases. Copyright © 2012 Society of Chemical Industry  相似文献