Yttrium 90 ibritumomab tiuxetan (Zevalin®): A new bullet in the fight against malignant lymphoma?

Targeted immunotherapy utilizing monoclonal antibodies has improved survival in both indolent and aggressive lymphoma significantly. Since malignant lymphomas are also responsive to radiation, the combination of targeted immunotherapy and radiation with radionuclide coupled to monoclonal antibodies is an attractive option to further improve treatment results. Zevalin is a commercially available variation of the murine anti-CD20 antibody ibritumomab coupled to Yttrium 90 via the tiuxetan chelator. The development of this novel drug as well as the results of the pivotal studies and clinical strategies to implement this treatment into the routine practice of lymphoma oncology are presented in this review.     

Forest health status in Europe

Forest health status in Europe is assessed by the International Cooperative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests). Established by the Convention on Long-Range Transboundary Air Pollution (CLRTAP) under the United Nations Economic Commission for Europe (UNECE), the ICP Forests has been monitoring forest condition in close cooperation with the European Commission (EC) for 20 years. The present paper describes the latest results of the deposition measurements on permanent monitoring plots and of the extensive defoliation sample survey. The findings reveal marked spatial patterns in bulk and throughfall depositions of nitrate (N-NO3(-)), ammonium (N-NH4(+)), and sulfate (S-SO4(2-)), as well as an obvious decrease in bulk and throughfall deposition of sulfate. Latest analyses of defoliation data confirm previous results, indicating a high correlation with weather extremes.     

Proteins reacting with anti-spectrin antibodies are present in Chlamydomonas cells.

It was found either in Western-blot analysis or in indirect immunofluorescence microscopy that cells of the alga Chlamydomonas reinhardtii contain polypeptides cross-reacting with antibodies directed against red blood cell spectrin. The protein could also be detected by immunoprecipitation with anti-spectrin antibodies. C. reinhardtii cells contain distinct polypeptide chains reacting with antibodies directed against either α- or β-spectrin subunits. This protein was extracted from the cells with low ionic strength solution but was not with nonionic detergent.     

Hiding Behaviour of Long-tailed Macaques (Macaca fascicularis): II. Use of Hiding Places during Aggressive Interactions

In an observational study on captive long-tailed macaques ( Macaca fascicularis ), the ability to hide was investigated in the social context of aggression. The use of five different types of hiding place during highly aggressive interactions was recorded and the choices of six different rank-sex classes were compared using an index of attractiveness of the different types of hiding place during highly aggressive interactions. There was no significant difference between the rank-sex classes in selection of the hiding places that could be connected with visibility: no specific location or type was preferred, either by the group as a whole or by any specific rank-sex class. Thus long-tailed macaques do not seem to hide shortly after aggressive interactions.     

Role of a JAK3-dependent biochemical signaling pathway in platelet activation and aggregation

Here we provide experimental evidence that identifies JAK3 as one of the regulators of platelet function. Treatment of platelets with thrombin induced tyrosine phosphorylation of the JAK3 target substrates STAT1 and STAT3. Platelets from JAK3-deficient mice displayed a decrease in tyrosine phosphorylation of STAT1 and STAT3. In accordance with these data, pretreatment of human platelets with the JAK3 inhibitor WHI-P131 markedly decreased the base-line enzymatic activity of constitutively active JAK3 and abolished the thrombin-induced tyrosine phosphorylation of STAT1 and STAT3. Following thrombin stimulation, WHI-P131-treated platelets did not undergo shape changes indicative of activation such as pseudopod formation. WHI-P131 inhibited thrombin-induced degranulation/serotonin release as well as platelet aggregation. Highly effective platelet inhibitory plasma concentrations of WHI-P131 were achieved in mice without toxicity. WHI-P131 prolonged the bleeding time of mice in a dose-dependent manner and improved event-free survival in a mouse model of thromboplastin-induced generalized and invariably fatal thromboembolism. To our knowledge, WHI-P131 is the first anti-thrombotic agent that prevents platelet aggregation by inhibiting JAK3.     

CNGA3 mutations in hereditary cone photoreceptor disorders

We recently showed that mutations in the CNGA3 gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated channel cause autosomal recessive complete achromatopsia linked to chromosome 2q11. We now report the results of a first comprehensive screening for CNGA3 mutations in a cohort of 258 additional independent families with hereditary cone photoreceptor disorders. CNGA3 mutations were detected not only in patients with the complete form of achromatopsia but also in incomplete achromats with residual cone photoreceptor function and (rarely) in patients with evidence for severe progressive cone dystrophy. In total, mutations were identified in 53 independent families comprising 38 new CNGA3 mutations, in addition to the 8 mutations reported elsewhere. Apparently, both mutant alleles were identified in 47 families, including 16 families with presumed homozygous mutations and 31 families with two heterozygous mutations. Single heterozygous mutations were identified in six additional families. The majority of all known CNGA3 mutations (39/46) are amino acid substitutions compared with only four stop-codon mutations, two 1-bp insertions and one 3-bp in-frame deletion. The missense mutations mostly affect amino acids conserved among the members of the cyclic nucleotide gated (CNG) channel family and cluster at the cytoplasmic face of transmembrane domains (TM) S1 and S2, in TM S4, and in the cGMP-binding domain. Several mutations were identified recurrently (e.g., R277C, R283W, R436W, and F547L). These four mutations account for 41.8% of all detected mutant CNGA3 alleles. Haplotype analysis suggests that the R436W and F547L mutant alleles have multiple origins, whereas we found evidence that the R283W alleles, which are particularly frequent among patients from Scandinavia and northern Italy, have a common origin.     

Organotin and osmoregulation: quantifying the effects of environmental concentrations of sediment-associated TBT and TPhT on the freshwater-adapted European flounder, Platichthys flesus (L.)

Chronic (5 weeks) exposure of freshwater-adapted European flounder, Platichthys flesus (L.), to environmental concentrations of sediment-associated tri-n-butyltin chloride (TBTCl) and triphenyltin chloride (TPhTCl) caused significant changes to hydromineral fluxes and membrane permeability, mechanisms that maintain osmotic homeostasis. The half-time of exchange of tritiated water (THO) in TBTCl- and TPhTCl-exposed fish was significantly increased during the first 2 weeks of the experiment and then decreased steadily, eventually reaching the level that the control group had constantly maintained throughout the experiment. This change in apparent water permeability was accompanied by a significant decrease in diffusional water flux across the membranes. Passive Na(+)-efflux across the gills was increased significantly but effluxes in the control group were near constant over the same time span. Drinking rates in the organotin groups increased significantly while the rate of urine production did not change. This lead to an increased net water balance in the organotin groups and consequently to a significant reduction of the blood osmolality of both organotin groups when compared to a control. There would appear to be a metabolic cost attached to the changes produced by exposure to environmental levels of organotin compounds which are manifested as a minimal increase in body length compared to the controls.     

Two distinct reproductive strategies are correlated with an ovarian phenotype in co-existing parthenogenetic strains of a parasitic wasp

The question whether different organisms are able to compete for the same resource is of fundamental importance to evolutionary biology. Sympatric co-existence of similar species on a single resource has long been claimed to be unstable. However, indirect evidence suggests that parasitic wasps exhibit evolutionarily stable mixtures of life-history strategies. Here we describe genetically distinct strains of a parthenogenetic wasp Venturia canescens, with different ovarian phenotypes that affect egg numbers in oviducts. Wasp females with large egg load search for caterpillars and deposit eggs immediately after host encounter, whereas females with fewer eggs delay parasitism. Since the outcome of interlarval competition within super-parasitized caterpillars depends on the age distribution of competing larvae, the two egg deposition strategies may co-exist under conditions that favor super-parasitism.