The Bs20x22 anti-CD20-CD22 bispecific antibody has more lymphomacidal activity than do the parent antibodies alone

Previous studies have shown that bispecific antibodies that target both CD20 and CD22 have in vivo lymphomacidal properties. We developed a CD20-CD22 bispecific antibody (Bs20x22) from anti-CD20 and the anti-CD22 monoclonal antibodies (mAb), rituximab and HB22.7, respectively. Bs20x22 was constructed using standard methods and was shown to specifically bind CD20 and CD22. In vitro cytotoxicity assays showed that Bs20x22 was three times more effective than either parent mAb alone and twice as effective as a combination of both parent mAb used at equimolar concentrations. Bs20x22 was also nearly four times more effective at inducing apoptosis than either mAb alone. Examination of the MAPK and SAPK signaling cascades revealed that Bs20x22 induced significantly more p38 phosphorylation than either mAb alone. In an in vivo human NHL xenograft model, treatment with Bs20x22 resulted in significantly greater tumor shrinkage and improved overall survival when compared to either mAb alone or treatment with a combination of HB22.7 and rituximab. The effect of the initial tumor volume was assessed by comparing the efficacy of Bs20x22 administered before xenografts grew versus treatment of established tumors; significantly, greater efficacy was found when treatment was initiated before tumors could become established

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

Acceptability of a Positive Parenting Programme on a Mother and Baby Unit: Q-Methodology with Staff

The Baby Triple P Positive Parenting Programme, a new addition to the established Triple P programmes, is currently being considered for a trial in a Mother and Baby Unit with the aim of exploring its benefits to mothers presenting with severe mental illness. The aim of the current study was to investigate staff views of the acceptability and feasibility of a parenting programme such as the Baby Triple P Positive Parenting Programme in a Mother and Baby Unit. Q-methodology, using an 88-item Q-sort, was employed to explore the opinions of 16 staff working in a Mother and Baby Unit in the North West of England. Results obtained from the Q-sort analysis identified two distinct factors: (1) staff qualified acceptance and (2) systemic approach/systemic results. Preliminary findings indicate that staff perceived Baby Triple P to be an acceptable and feasible intervention for the Mother and Baby Unit setting and that mothers on the unit would be open and receptive to the programme. Further research is required to expand these findings and assess the potential for this type of intervention to be used more widely across a number of Mother and Baby Unit settings

Additions to the Mycosphaerella complex

Species in the present study were compared based on their morphology, growth characteristics in culture, and DNA sequences of the nuclear ribosomal RNA gene operon (including ITS1, ITS2, 5.8S nrDNA and the first 900 bp of the 28S nrDNA) for all species and partial actin and translation elongation factor 1-alpha gene sequences for Cladosporium species. New species of Mycosphaerella (Mycosphaerellaceae) introduced in this study include M. cerastiicola (on Cerastium semidecandrum, The Netherlands), and M. etlingerae (on Etlingera elatior, Hawaii). Mycosphaerella holualoana is newly reported on Hedychium coronarium (Hawaii). Epitypes are also designated for Hendersonia persooniae, the basionym of Camarosporula persooniae, and for Sphaerella agapanthi, the basionym of Teratosphaeria agapanthi comb. nov. (Teratosphaeriaceae) on Agapathus umbellatus from South Africa. The latter pathogen is also newly recorded from A. umbellatus in Europe (Portugal). Furthermore, two sexual species of Cladosporium (Davidiellaceae) are described, namely C. grevilleae (on Grevillea sp., Australia), and C. silenes (on Silene maritima, UK). Finally, the phylogenetic position of two genera are newly confirmed, namely Camarosporula (based on C. persooniae, teleomorph Anthracostroma persooniae), which is a leaf pathogen of Persoonia spp. in Australia, belongs to the Teratosphaeriaceae, and Sphaerulina (based on S. myriadea), which occurs on leaves of Fagaceae (Carpinus, Castanopsis, Fagus, Quercus), and belongs to the Mycosphaerellaceae

Short-term stability in refractive status despite large fluctuations in glucose levels in diabetes mellitus type 1 and 2

Purpose: This work investigates how short-term changes in blood glucose concentration affect the refractive components of the diabetic eye in patients with long-term Type 1 and Type 2 diabetes. Methods: Blood glucose concentration, refractive error components (mean spherical equivalent MSE, J0, J45), central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), axial length (AL) and ocular aberrations were monitored at two-hourly intervals over a 12-hour period in: 20 T1DM patients (mean age ± SD) 38±14 years, baseline HbA1c 8.6±1.9%; 21 T2DM patients (mean age ± SD) 56±11 years, HbA1c 7.5±1.8%; and in 20 control subjects (mean age ± SD) 49±23 years, HbA1c 5.5±0.5%. The refractive and biometric results were compared with the corresponding changes in blood glucose concentration. Results: Blood glucose concentration at different times was found to vary significantly within (p0.05). Minor changes of marginal statistical or optical significance were observed in some biometric parameters. Similarly there were some marginally significant differences between the baseline biometric parameters of well-controlled and poorly-controlled diabetic subjects. Conclusion: This work suggests that normal, short-term fluctuations (of up to about 6 mM/l on a timescale of a few hours) in the blood glucose levels of diabetics are not usually associated with acute changes in refractive error or ocular wavefront aberrations. It is therefore possible that factors other than refractive error fluctuations are sometimes responsible for the transient visual problems often reported by diabetic patients

Clinical practice: neonatal resuscitation. A Dutch consensus

The updated Dutch guidelines on Neonatal Resuscitation assimilate the latest evidence in neonatal resuscitation. Important changes with regard to the 2004 guidelines and controversial issues concerning neonatal resuscitation are reviewed, and recommendations for daily practice are provided and argued in the context of the ILCOR 2005 consensus

Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration.

Understanding the molecular mechanisms that promote successful tissue regeneration is critical for continued advancements in regenerative medicine. Vertebrate amphibian tadpoles of the species Xenopus laevis and Xenopus tropicalis have remarkable abilities to regenerate their tails following amputation, through the coordinated activity of numerous growth factor signalling pathways, including the Wnt, Fgf, Bmp, Notch and TGF-β pathways. Little is known, however, about the events that act upstream of these signalling pathways following injury. Here, we show that Xenopus tadpole tail amputation induces a sustained production of reactive oxygen species (ROS) during tail regeneration. Lowering ROS levels, using pharmacological or genetic approaches, reduces the level of cell proliferation and impairs tail regeneration. Genetic rescue experiments restored both ROS production and the initiation of the regenerative response. Sustained increased ROS levels are required for Wnt/β-catenin signalling and the activation of one of its main downstream targets, fgf20 (ref. 7), which, in turn, is essential for proper tail regeneration. These findings demonstrate that injury-induced ROS production is an important regulator of tissue regeneration

Habitat and Host Indicate Lineage Identity in Colletotrichum gloeosporioides s.l. from Wild and Agricultural Landscapes in North America

Understanding the factors that drive the evolution of pathogenic fungi is central to revealing the mechanisms of virulence and host preference, as well as developing effective disease control measures. Prerequisite to these pursuits is the accurate delimitation of species boundaries. Colletotrichum gloeosporioides s.l. is a species complex of plant pathogens and endophytic fungi for which reliable species recognition has only recently become possible through a multi-locus phylogenetic approach. By adopting an intensive regional sampling strategy encompassing multiple hosts within and beyond agricultural zones associated with cranberry (Vaccinium macrocarpon Aiton), we have integrated North America strains of Colletotrichum gloeosporioides s.l. from these habitats into a broader phylogenetic framework. We delimit species on the basis of genealogical concordance phylogenetic species recognition (GCPSR) and quantitatively assess the monophyly of delimited species at each of four nuclear loci and in the combined data set with the genealogical sorting index (gsi). Our analysis resolved two principal lineages within the species complex. Strains isolated from cranberry and sympatric host plants are distributed across both of these lineages and belong to seven distinct species or terminal clades. Strains isolated from V. macrocarpon in commercial cranberry beds belong to four species, three of which are described here as new. Another species, C. rhexiae Ellis & Everh., is epitypified. Intensive regional sampling has revealed a combination of factors, including the host species from which a strain has been isolated, the host organ of origin, and the habitat of the host species, as useful indicators of species identity in the sampled regions. We have identified three broadly distributed temperate species, C. fructivorum, C. rhexiae, and C. nupharicola, that could be useful for understanding the microevolutionary forces that may lead to species divergence in this important complex of endophytes and plant pathogens