Metastasis-associated protein S100A4 induces a network of inflammatory cytokines that activate stromal cells to acquire pro-tumorigenic properties

Tumor cells have the ability to exploit stromal cells to facilitate metastasis. By using malignant melanoma as a model, we show that the stroma adjacent to metastatic lesions is enriched in the known metastasis-promoting protein S100A4. S100A4 stimulates cancer cells to secrete paracrine factors, such as inflammatory cytokines IL8, CCL2 and SAA, which activate stromal cells (endothelial cells and monocytes) so that they acquire tumor-supportive properties. Our data establishes S100A4 as an inducer of a cytokine network enabling tumor cells to engage angiogenic and inflammatory stromal cells, which might contribute to pro-metastatic activity of S100A4.     

The targeting,docking and anti-proteolysis functions of the secretin chaperone PulS

The Klebsiella oxytoca lipoprotein PulS might function as either or both a pilot and a docking factor in the outer membrane targeting and assembly of the Type II secretion system secretin PulD. In the piloting model, PulS binds to PulD monomers and targets them to the outer membrane via the lipoprotein sorting pathway components LolA and LolB. In this model, PulS also protects the PulD monomers from proteolysis during transit through the periplasm. In the docking model, PulS is targeted alone to the outer membrane, where it acts as a receptor for PulD monomers, allowing them to accumulate and assemble specifically in this membrane. PulS was shown to dissociate from and/or re-associate freely with PulD multimers in zwitterionic detergent, making it difficult to determine whether PulS remains associated with PulD dodecamers in the outer membrane by co-purification. However, PulD protomers in the dodecamer were shown to be stable in the absence of PulS, indicating that PulS is only required to protect the protease-susceptible monomer. DegP was identified as one of the proteases that could contribute to PulD degradation in the absence of PulS. Studies on the in vitro assembly and targeting of PulD into Escherichia coli membrane vesicles demonstrated its strong preference to insert into the inner membrane, as is the case in vivo in the absence of PulS. However, PulD could be targeted to outer membrane fragments in vitro if they were preloaded with PulS, indicating the technical feasibility of the docking model. We conclude that both modes of action might contribute to efficient outer membrane targeting of PulD in vivo, although the piloting function is likely to predominate.     

Reduced quality of life in living kidney donors: association with fatigue, societal participation and pre-donation variables

Health related quality of life (HRQoL) of living kidney donors on average is good, but some donors experience a low HRQoL after donation. This study assessed the prevalence of reduced HRQoL and explored associations with pre‐ and post‐donation variables. 316 donors (response rate 74%) who donated a kidney between 1997 and 2009 filled in a questionnaire. HRQoL was measured using the Short‐Form 36; fatigue using the Multidimensional Fatigue Inventory; societal participation using the Utrecht Scale for Evaluation of Rehabilitation‐Participation. Donors on average had better HRQoL than the general population. However, 12% had a reduced physical (PCS) and 18% a reduced mental (MCS) HRQoL. Donors with reduced HRQoL reported greater fatigue (P < 0.01), lower societal participation (P < 0.01) and showed a trend towards statistical significance in experiencing more donor–recipient relationship changes (P = 0.07). Prior to donation, donors with reduced PCS had a higher BMI (P < 0.05) and more often smoked (P < 0.05). Donors with reduced MCS had higher expectations (P < 0.05). Reduced HRQoL is associated with higher BMI, smoking and higher expectations prior to donation. These results may be used to develop a screening instrument to select donors at high risk for reduced HRQoL.     

Activity restrictions after gynecologic surgery: is there evidence?

Many surgeons recommend rest and restricting activities to their patients after surgery. The aim of this review is to summarize the literature regarding types of activities gynecologic surgeons restrict and intra-abdominal pressure during specific activities and to provide an overview of negative effects of sedentary behavior (rest). We searched PubMed and Scopus for years 1970 until present and excluded studies that described recovery of activities of daily living after surgery as well as those that assessed intra-abdominal pressure for other reasons such as abdominal compartment syndrome and hypertension. For our review of intra-abdominal pressure, we excluded studies that did not include a generally healthy population, or did not report maximal intra-abdominal pressures. We identified no randomized trial or prospective cohort study that studied the association between postoperative activity and surgical success after pelvic floor repair. The ranges of intra-abdominal pressures during specific activities are large and such pressures during activities commonly restricted and not restricted after surgery overlap considerably. There is little concordance in mean peak intra-abdominal pressures across studies. Intra-abdominal pressure depends on many factors, but not least the manner in which it is measured and reported. Given trends towards shorter hospital stays and off work intervals, which both predispose women to higher levels of physical activity, we urge research efforts towards understanding the role of physical activity on recurrence of pelvic organ prolapse and urinary incontinence after surgery.     

FCGR3A V(176) polymorphism for systemic lupus erythematosus susceptibility in Mexican population

The objective of this study is to establish whether there is an association between the presence of FCGR3A V(176) polymorphism with SLE or its manifestations. We included 94 patients according to the 1982 ACR criteria as well as 98 controls matched by age and gender. The 11 ACR diagnostic criteria were analyzed on the clinical files. The polymorphism FCGR3A V(176) was determined by direct sequencing. There was not an association between the polymorphism FCGR3A V(176) with SLE or its main manifestations. The allelic frequency for F(176) was: 0.80 and 0.72 in cases and controls, respectively (P?=?0.09, IC95%: 0.42?C1.07); and the genotypic frequency in the group of cases was: 0.65 for homozygotes F(176)/F(176), 0.30 for heterozygotes and 0.05 for the homozygotes V(176)/V(176), while for the control group it was 0.53, 0.39 and 0.08, respectively. The polymorphism FCGR3A V(176) is not associated with SLE or any of its manifestations in patients with SLE from the West of Mexico.