Correction to: Overall survival analysis in patients with metastatic breast cancer and liver or lung metastases treated with eribulin,gemcitabine, or capecitabine

Breast Cancer Research and Treatment - In the original publication, two values provided for landmark survival for patients treated with gemcitabine were incorrectly listed in the text. On page 562,...     

Expression of phosphorylcholine-specific B cells during murine development

The TEPC 15 (T15) clonotype, a putatively germline antibody specificity, does not appear in the neonatal B-cell repertoire until approximately 1 wk of age. This report extends this observation by the demonstration that (a) the T15 clonotype follows similar kinetics of appearance in germfree as well as conventionally-reared mice; (b) maternal influences and genetic background play a minor role in the development of the T15 clonotype since CBFI neonates raised by C57BL/6 or BALB/c mothers acquire the T15 clonotype at the same time in ontogeny as BALB/c neonates; (c) the lack of phosphorylcholine (PC)-specific B cells shortly after birth is reflected in a dearth of PC-binding cells in the neonate as well; and (d) no PC-specifc B cells are found in 19-day fetal liver or in bone marrow until 7 days of life, coincident with their appearance in the spleen. These findings, along with a previous report that PC-specific splenic B cells are tolerizable as late as day 10 after birth, confirm the invariant, late occurrence of the T15 clonotype and support a highly- ordered, rigorously predetermined mechanism for the acquisition of the B- cell repertoire. The results are discussed in light of other studies on the ontogeny of B-cell specificity, and in terms of the implications on the mechanism by which antibody diversity is generated.     

Hyaluronan-dependent motility of B cells and leukemic plasma cells in blood, but not of bone marrow plasma cells, in multiple myeloma: alternate use of receptor for hyaluronan-mediated motility (RHAMM) and CD44

We investigated the ability of blood B cells, bone marrow (BM) plasma cells, and terminal leukemic plasma cells (T-PCL) from patients with multiple myeloma (MM) to migrate on extracellular matrix proteins. Hyaluronan (HA), but not collagen type I, collagen type IV, or laminin, promoted migration of MM blood B cells, as determined by time-lapse video microscopy. Between 13% and 20% of MM blood B cells migrated on HA with an average velocity of 19 micron/min, and greater than 75% of MM blood B cells exhibited vigorous cell movement and plasma membrane deformation, as did circulating T-PCL and extraskeletal plasma cells from patients with MM. In contrast, plasma cells obtained from BM of patients with MM lacked motility on all substrates tested and did not exhibit cell membrane protrusions or cellular deformation. MM blood B cells and MM plasma cells from all sources examined expressed the HA- binding receptors receptor for HA-mediated motility (RHAMM) and CD44. On circulating MM B cells, both RHAMM and CD44 participated in HA- binding, indicating their expression ex vivo in an activated conformation. In contrast, for the majority of BM plasma cells in the majority of patients with MM, expression of RHAMM or CD44 was not accompanied by HA binding. A minority of patients did have HA-binding BM plasma cells, involving both RHAMM and CD44, as evidenced by partial blocking with monoclonal antibodies (MoAbs) to RHAMM or to CD44. Despite HA binding by both RHAMM and CD44, migration of MM blood B cells on HA was inhibited by anti-RHAMM but not by anti-CD44 MoAbs, indicating that RHAMM but not CD44 mediates motility on HA. Thus, circulating B and plasma cells in MM exhibit RHAMM- and HA-dependent motile behavior indicative of migratory potential, while BM plasma cells are sessile. We speculate that a subset(s) of circulating B or plasma cells mediates malignant spread in myeloma.     

Prognostic value of psychosocial factors for first and recurrent hospitalizations and mortality in heart failure patients: insights from the OPERA‐HF study

Aims

Psychosocial factors are rarely collected in studies investigating the prognosis of patients with heart failure (HF), and only time to first event is commonly reported. We investigated the prognostic value of psychosocial factors for predicting first or recurrent events after discharge following hospitalization for HF.

Methods and results

OPERA‐HF is an observational study enrolling patients hospitalized for HF. In addition to clinical variables, psychosocial variables are recorded. Patients provide the information through questionnaires that include social information, depression and anxiety scores, and cognitive function. Kaplan–Meier, Cox regression and the Andersen–Gill model were used to identify predictors of first and recurrent events (readmissions or death). Of 671 patients (age 76 ± 15 years, 66% men) with 1‐year follow‐up, 291 had no subsequent event, 34 died without being readmitted, 346 had one or more unplanned readmissions, and 71 patients died after a first readmission. Increasing age, higher urea and creatinine, and the presence of co‐morbidities (diabetes, history of myocardial infarction, chronic obstructive pulmonary disease) were all associated with increasing risk of first or recurrent events. Psychosocial variables independently associated with both the first and recurrent events were: presence of frailty, moderate‐to‐severe depression, and moderate‐to‐severe anxiety. Living alone and the presence of cognitive impairment were independently associated only with an increasing risk of recurrent events.

Conclusion

Psychosocial factors are strongly associated with unplanned recurrent readmissions or mortality following an admission to hospital for HF. Further research is needed to show whether recognition of these factors and support tailored to individual patients' needs will improve outcomes.

     

Expanding applications,accuracy, and interpretation of laser speckle contrast imaging of cerebral blood flow

Laser speckle contrast imaging (LSCI) provides a rapid characterization of cortical flow dynamics for functional monitoring of the microcirculation. The technique stems from interactions of laser light with moving particles. These interactions encode the encountered Doppler phenomena within a random interference pattern imaged in widefield, known as laser speckle. Studies of neurovascular function and coupling with LSCI have benefited from the real-time characterization of functional dynamics in the laboratory setting through quantification of perfusion dynamics. While the technique has largely been relegated to acute small animal imaging, its scalability is being assessed and characterized for both chronic and clinical neurovascular imaging.     

Progress and prospects for the use and the understanding of the mode of action of autologous hematopoietic stem cell transplantation in the treatment of multiple sclerosis

Introduction: A substantial proportion of patients with multiple sclerosis (MS) do not respond to pharmacological treatments and no currently approved therapy has been convincingly demonstrated to prevent or stop disease progression. With MS widely believed to be an auto-immune disease, immunoablative therapy followed by autologous haematopoietic stem cell transplantation (I/AHSCT) is being investigated as an alternative therapeutic option.

Areas covered: With the results of phase III comparative trials only a few years away, this article reviews animal and clinical trials of I/AHSCT in the treatment of MS and discusses possible immunological mechanisms behind its action.

Expert commentary: I/AHSCT can induce long-term suppression of inflammatory disease activity and can halt or reverse neurological deterioration even in progressive stages of the disease, altering the fundamental disease course. However, toxicity of the therapy remains a problem and longer term follow up is required. Immunological investigations of the reconstituting immune system have discovered that qualitative changes take place at the cellular and molecular levels, which support the hypothesis of a ‘resetting’ of the immune system towards a tolerant and anti-inflammatory state.     

Evidence for direct action of human biosynthetic (recombinant) GM-CSF on erythroid progenitors in serum-free culture

The biologic activity of human biosynthetic granulocyte-monocyte colony stimulating factor (GM-CSF) was investigated in serum-free culture of erythroid progenitors derived from adult peripheral blood. The morphology of erythroid bursts and the cloning efficiency of BFU-E under serum-free conditions were similar to those observed in dishes with fetal bovine serum (FBS). For these experiments, progenitor cells were partially purified by Ficoll-Paque density centrifugation, adherence to a plastic surface, and complement-mediated cytotoxicity of Leu-1+ elements. For some studies, blastlike cells were harvested directly from 6-day-old semisolid cultures. In serum-free culture of the light-density cell fraction, biosynthetic erythropoietin (Ep) was sufficient for formation of pure and mixed erythroid colonies whereas GM-CSF was required for granulocyte-monocytic colonies. When adherent and Leu-1+ cells were removed, or when in vitro differentiated blast cells were used as a source of progenitors, neither Ep or GM-CSF alone induced colony formation. In dishes supplemented with both growth factors, erythroid bursts were detected. Although the presence of GM- CSF alone did not induce formation of any colony or clusters, BFU-E were recorded when Ep was added 8 days later, suggesting that BFU-E could be maintained. Terminal maturation of the resulting erythroid bursts was delayed by 8 days. These results provide evidence that GM- CSF acts directly on early erythroid progenitors. Furthermore, they suggest that both Ep and GM-CSF are necessary to start the differentiation process.     

Hair Contamination of Sheepdog and Pet Dogs with Toxocara canis Eggs

Background

We tried to investigate the hair contamination of pet dogs and farm sheepdog with Toxocara eggs in terms of the different sex and age groups in north-west of Iran (Urmia and its suburbs).

Methods

Hair samples were collected from a total of 138 pet and farm sheepdogs from November 2008 to June 2009 in Urmia City and the suburb (West Azerbaijan-Iran) and examined for the presence of T. canis eggs.

Results

T. canis eggs found in 60 samples altogether (pet and shepherd dogs) showed a contamination rate of 36.2%. The number of observed T. canis eggs in each microscope field was varied from 1 to > 400. The age of the dog was found a significant factor to influence the prevalence and intensity of contamination, with 82% of all the eggs recovered from puppies (six months and younger). Additionally, the numbers of eggs in farm sheepdogs were significantly higher than pet dogs (P<0.05).

Conclusion

This report shows that direct contact with T. canis infected dogs, particularly puppies from shepherd dogs, may pose a serious hazard to human. Besides, as they may harbor a considerable number of eggs on their hair, they can contaminate the soil and the environment.