Brevican knockdown reduces late-stage glioma tumor aggressiveness

Growing evidence supports the important role of the tumor microenvironment (TME) in cancer biology. A defining aspect of the glioma TME is the unique composition and structure of its extracellular matrix (ECM), which enables tumor cells to overcome the inhibitory barriers of the adult central nervous system (CNS). In this way, the TME plays a role in glioma invasion and the cellular heterogeneity that distinguishes these tumors. Brain Enriched Hyaluronan Binding (BEHAB)/brevican (B/b), is a CNS-specific ECM constituent and is upregulated in the glioma TME. Previous studies have shown B/b exerts a pro-invasive function, suggesting it may represent a target to reduce glioma pathogenesis. Herein, we also provide evidence that B/b expression is enriched in the glioma initiating cell (GIC) niche. We demonstrate that B/b plays roles in the pathological progression, aggressiveness, and lethality of tumors derived from human GICs and traditional glioma cell lines. Interestingly, we found that B/b is not required to maintain the defining phenotypic properties of GICs and thereby acts primarily in late stages of glioma progression. This study suggests that the increased expression of B/b in the TME is a valuable therapeutic target for glioma.     

Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of ischemic stroke: a meta-analysis.

This study investigated the hypothesis that the insertion/deletion (4G/5G) polymorphism of the plasminogen activator inhibitor type-1 gene affects the risk for ischemic stroke, since results concerning this association have been controversial. We therefore performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out until January 2006. The analysis was performed using random-effects models and meta-regression. Eighteen eligible studies were retrieved (15 case-control studies and three cohort studies). The case-control studies included 3104 cases and 4870 control individuals concerning the contrast of 4G/4G versus remaining genotypes. The 4G pooled allele frequencies in cases and controls were 54.21 and 54.75%, respectively. Overall, the per-allele odds ratio of the 4G allele was 0.98 (95% confidence interval, 0.858-1.121). Regarding genotypes, we derived nonsignificant odds ratios in all contrasts. The subanalysis including the three studies with a prospective design in the 4G/4G versus 5G/5G contrast derived a significant result (relative risk, 0.523; 95% confidence interval, 0.353-0.775), but the estimated effect size was insignificant when cohort and case-control studies were analyzed together (relative risk, 0.848; 95% confidence interval, 0.662-1.087). We failed to demonstrate a significant association between the 4G/5G polymorphism and ischemic stroke under basal conditions. Determination of plasminogen activator inhibitor type-1 function seems of much higher clinical value than determination of the 4G/5G polymorphism. The effect of this genotype on risk of ischemic stroke in acute stressful diseases and the role of cohort studies in genetic epidemiology, however, warrant further investigation.     

Lower gastrointestinal haemorrhage secondary to an ileal lipoma protruding into the caecum

We report the case of a patient with lower gastrointestinal haemorrhage. The cause of the haemorrhage was a lipoma of the terminal ileum that protruded into the caecum. The diagnosis was made endoscopically and radiologically. It was surgically treated with local excision.     

Evaluation of a quantitative diagnostic sacroiliac bone scan index in cases of chronic low back pain in young male adults

Quantitative bone scan of the sacroiliac joints has long been an established diagnostic method in cases of chronic low back pain (LBP), though its value has been questioned due to the significant overlap of the numerical values between patients with inflammatory sacroiliitis and healthy controls. In an effort to solve this dissent, 133 young male adults aged 18-36 years were studied. We thus aimed to have a relatively homogenous population sample that would include the age that many sacroiliac diseases appear. Thirty-two of our patients had chronic, inflammatory disease of non-infectious origin, as tested by clinicolaboratory procedures (Group A), 29 had mechanical (non-inflammatory type) LBP (Group B), and 72 had been scintiscanned for reasons irrelevant to spine disease (Group C). The members of each group were also classified in three subgroups (a, b and c) according to age. The protocol of planar static multispot bone scan was applied to all three Groups. Three regions of interest (ROI), two on the sacroiliac joints plus one over the L4 vertebra were drawn and finally a non-dimensional numerical parameter called "lambda" was extracted by the equation lambda=total counts/total pixels of the "hottest" of the two sacroiliac joints area divided by the counts/pixels corresponding to the L4 values (lambda=SI/L4). The statistical analysis showed negative correlation of lambda with age in all three groups (P~0.04 for Group A, P~0.012 for Group B and P~0.05 for Group C). When all Groups were examined regardless of age, lambda appeared significantly different (P<0.0005) between Groups A and C, as well as between Groups A and B (P~0.002) but there was no difference between Groups B and C (P~0.12). When the members of each group were analyzed according to age, the paired difference of lambda stirred with remarkable vagueness along the whole spectrum of statistical significance. Conclusively, lambda seems to decrease with ageing at ages ranging from 18 to 36 years (P相似文献   

Localization of myosin II regulatory light chain in the cerebral vasculature

The cytoskeleton of cerebral microvascular endothelial cells is a critical determinant of blood-brain barrier (BBB) function. Barrier integrity appears to be particularly sensitive to the phosphorylation state of specific residues within myosin regulatory light chain (RLC), one of two accessory light chains of the myosin II motor complex. Phosphorylation of myosin RLC by myosin light chain kinase (MLCK) has been implicated in BBB dysfunction associated with alcohol abuse and hypoxia, whereas dephosphorylation may enhance BBB integrity following exposure to lipid-lowering statin drugs. Using immunohistochemistry we provide evidence of widespread myosin II RLC distribution throughout the cerebral vasculature of the mouse. Light microscopy revealed immunolocalization of myosin II RLC protein in the endothelium of brain capillaries, the endothelial cell layer of arterioles and in association with venules. Immunolabeling of myosin RLC in non-muscle endothelial cells could be distinguished from myosin RLC immunoreactivity associated with the smooth muscle layer of the tunica media in larger muscular arterioles. These findings support an emerging role for myosin II RLC as a component of the actomyosin cytoskeleton of cerebral endothelial cells with the potential to contribute to the selective vulnerability of the brain in vivo.     

Laparoscopic transabdominal preperitoneal repair of inguinal hernia under spinal anesthesia: a pilot study

Background

The laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair is an evolving technique associated with the well-known advantages of a minimally invasive approach. However, general anesthesia is routinely required for the procedure. Based on our previous experience in regional anesthesia for laparoscopic procedures, we designed a pilot study to assess the feasibility and safety of performing laparoscopic TAPP repair under spinal anesthesia.

Methods

Forty-five American Society of Anesthesiologists I or II patients with a total of 50 inguinal hernias underwent TAPP repair under spinal anesthesia, using a low-pressure CO₂ pneumoperitoneum. Five patients had bilateral hernias, and 4 patients had recurrent hernias. Thirty hernias were indirect and the remaining direct. Intraoperative incidents, postoperative pain complications, and recovery in general as well as patient satisfaction at the follow-up examination were prospectively recorded.

Results

There was 1 conversion from spinal to general anesthesia and 2 conversions from laparoscopic to the open procedure at a median operative time of 50 minutes (range 30-130). Ten patients complained of shoulder pain during the procedure, and 6 patients suffered hypotension intraoperatively. The median pain score (visual analog scale) was 1 (0-5) at 4 hours after the completion of the procedure, 1.5 (0-6) at 8 hours, and 1.5 (0-5) at 24 hours, and the median hospital stay was 1 day (range 1-2). Sixteen patients had urinary retention requiring instant catheterization. At a median follow-up of 20 months (range 10 months-28 months), no recurrence was detected.

Conclusions

TAPP repair is feasible and safe under spinal anesthesia. However, it seems to be associated with a high incidence of urinary retention. Further studies are required to validate this technique.