Diffuse large B-cell lymphoma (DLBCL) is the most common and one of the most aggressive subtypes of non-Hodgkin’s lymphomas. Front-line therapy consists of chemotherapy in combination with anti-CD20 monoclonal antibody rituximab. Relapses after rituximab-based regimen have poor prognosis and call for new treatment options. Immunohistochemistry analysis of relapsed DLBCL often reveal CD20-negative lymphoma, which limits repeated use of rituximab in combination with salvage chemotherapy. CD38 is a surface antigen that binds to CD38, CD31/PECAM-1 and hyaluronic acid. CD38 is an important mediator of signal transmission from the microenvironment into the cell. Anti-CD38 monoclonal antibody daratumumab has been approved for the treatment of multiple myeloma. Expression of CD38 on the surface of DLBCL is highly variable (compared to strong expression on myeloma cells), but can be easily assessed by flow cytometry or immunohistochemistry. A patient-derived xenograft (PDX) model of CD20-negative, CD38-positive DLBCL derived from a patient with rituximab-refractory DLBCL was used for in vivo experiments. We demonstrated that daratumumab suppressed growth of subcutaneous PDX tumours significantly more effectively than rituximab. Analysis of tumours obtained from mice treated with daratumumab revealed down-regulation of surface CD38, suggesting endocytosis of CD38-daratumumab complexes. The results suggest a potential clinical use of daratumumab in combination with salvage chemotherapy in patients with relapses of CD20-negative DLBCL. In addition, daratumumab might potentially serve as a suitable antibody moiety for derivation of antibodydrug conjugates for the targeted delivery of toxic payloads to the lymphoma cells.
The development of Myxobolus dispar Thélohan, 1895, a myxosporean parasite of the gills of common carp (Cyprinus carpio L.) was studied in experimentally infected oligochaetes Tubifex tubifex Muller. After infection of uninfected tubificids with mature spores of M. dispar, development of actinosporean stages was first observed light microscopically 21 days after initial exposure. In histological sections, early pansporocysts were located in the gut epithelium of experimental oligochaetes, while advanced stages occupied mostly the outer layers of the gut and the coelozoic space. Mature pansporocysts, each containing 8 raabeia spores, appeared 199 days after initial exposure. Following damage of the intestinal wall and rupture of the pansporocysts, free actinosporean stages were found in the gut lumen of the oligochaetes. Actinospores of hi. dispar emerged from the worms after 217 days of intra-oligochaete development. They were floating in the water and showed a unique raabeia form. Each raabeia spore had three pyriform polar capsules and a cylindrical-shaped sporoplasm with approximately 32 secondary cells. The spore body joined the three caudal projections without a style. Caudal projections were bifurcated at the end and the two main branches had further small bifurcations. The total length of the raabeia spore was approximately 158 pm. The prevalence of infection in 240 experimentally infected Tubifex specimens was 99.2%. No infection was found in the control oligochaetes.
A new multivalvulid myxosporean species, Kudoa dianae sp. n., is described from bullseye puffer, Sphoeroides annulatus (Jenyns) (Tetraodontiformes: Tetraodontidae). Plasmodia develop in extramuscular sites, in the wall of oesophagus and less frequently on mesenteries. Mature spores can reach lumen of the digestive tract directly by disruption of plasmodial wall or via macrophage transport to the oesophageal epithelium. New species is characterised by morphology of spores and by the complete sequence of SSU rRNA gene that differs from all hitherto known sequences of Kudoa species. Spore morphology (moderate-sized, simple non-ornate spores, quadrate in apical view) clusters with that of Kudoa scienae, K. cerebralis, K. chilkaensis, K. leiostomi, K. funduli, K. cascasia and K. ovivora. Analysis of phylogenetic relationships (using SSU rRNA gene sequences) among five Kudoa species, the molecular data of which are available thus far, revealed that K. dianae is distinguishable from these five species and that its closest relation is with K. miniauriculata.
Charactenstícs of the pigment apparatus were studied in plants grown from tubers of the oř 3’’^ doně generation of two cultivars of potato (Solanum tuberosum L) transformed with Agrobacterium tumefaciens strains. The cv. Zvíkov carries pRiA4b T-DNA of A. rhizogenes and the vector plasmid pGA472 T-DNA carrying the gene for kanamycin resistance. The cv. Kamýk carries the vector plasmid pCB1339 which contains the kanamycin resistance gene and the cytokinin synthesis gene. In the field experiments, the plant dry matter, the relative water content, the chlorophyll (Chl) a and b contents, the Chl a/b ratio and the course of slow Chl fluorescence induction curves were not signifícantly different in transformed and control plants. The amoímt of the Chl-protein complexes of the reaction centres of both photosystems separated by electrophoresis was similar for both transformed and control plants. Howevér, the content of oligomeric light-harvesting complex was significantly higher in both the transformants.
Two cultivars of bean, Tacarigua and VUL 73-401 were subjected to two levels of water stress followed by rewatering. During the water deficit period, water potential (Ψ№), osmotic potential (Ψ5) and relative water content (rwc) decreased with an associated decrease of ribulose-l,5-bisphosphate carboxylase activity (RuBPC), protein and chlorophyll (Chi) contents. In cv. Tacarigua, the % decrease of RuBPC was less marked than that of protein content. There was a significant correlation among the components of leaf water status and the measured photosynthetic parameters. Groups of water stressed plants were rewatered, when reached -1.25 to -1.60 MPa. During the recovering period all components of leaf water status increased and reached the control values on the 6th day after rewatering. Chi content increased above the control values. Protein content and RuBPC activity also increased during the rewatering period, but the % increases in protein content and RuBPCase activity were not parallel.