Sonic hedgehog is required during an early phase of oligodendrocyte development in mammalian brain.

Oligodendrocyte precursor development in the embryonic spinal cord is thought to be regulated by the secreted signal, Sonic hedgehog (Shh). Such precursors can be identified by the expression of Olig genes, encoding basic helix-loop-helix factors, in the spinal cord and brain. However, the signaling pathways that govern oligodendrocyte precursor (OLP) development in the rostral central nervous system are poorly understood. Here, we show that Shh is required for oligodendrocyte development in the mouse forebrain and spinal cord, and that Shh proteins are both necessary and sufficient for OLP production in cortical neuroepithelial cultures. Moreover, adenovirus-mediated Olig1 ectopic expression can promote OLP formation independent of Shh activity. Our results demonstrate essential functions for Shh during early phases of oligodendrocyte development in the mammalian central nervous system. They further suggest that a key role of Shh signaling is activation of Olig genes.     

Response to travoprost in black and nonblack patients with open-angle glaucoma or ocular hypertension

Two prospective, controlled, multicenter, double-masked studies—one lasting 6 months (n=594) and the other, 12 months (n=787)—examined the intraocular pressure (IOP)-lowering efficacy of travoprost in 1381 black and nonblack patients with open-angle glaucoma or ocular hypertension. Investigated regimens were travoprost 0.004% once daily, latanoprost 0.005% once daily, and timolol 0.5% twice daily. In both studies, mean IOP was significantly lower in blacks treated with travoprost. The IOP reduction was also significantly greater in blacks after adjustments for age, sex, iris color, diagnosis, and corneal thickness. Timolol lowered mean IOP to a greater extent in nonblack patients. The significantly larger IOP reduction with travoprost compared with timolol in both racial groups was more pronounced in blacks. Travoprost also was superior to latanoprost in blacks. Mean changes from baseline generally were greater for black than for nonblack patients, although the differences did not achieve statistical significance. The response rate to travoprost was higher in blacks. The most common adverse effect was hyperemia.     

Thoracic endovascular aortic repair migration and aortic elongation differentiated using dual reference point analysis

Objective

We evaluated images of patients undergoing a thoracic endovascular aortic repair procedure using two reference points as a means for differentiating stent graft migration from aortic elongation. Conventional standards define migration of a stent graft as an absolute change in the distance from the distal graft ring to a distal landmark ≥10 mm compared with a baseline measurement. Aortic elongation occurs over time in both healthy individuals and patients with aortic disease. Aortic elongation in patients with stent grafts may result in increased distal thoracic aortic lengths over time. False-positive stent graft migration would be defined when these patients meet the standard definition for migration, even if the stent has not moved in relation to the elongating aorta.

Lymphocytopenia as a marker for pandemic influenza A/H1N1 2009 virus infection in children

Lymphocytopenia has been reported in adults with pandemic influenza A/H1N1 2009 infection, but data in children are inconclusive. Data from 76 children presented with flu‐like symptoms between July and November 2009 and tested for pandemic influenza A/H1N1 2009 virus and white blood cell (WBC) counts were analyzed. Samples from 37 (48.7%) children resulted in a positive PCR assay for pandemic influenza A/H1N1 2009 virus. When comparing data from these children with data from 39 (51.3%) children with uncomplicated flu‐like illness and negative PCR assay for pandemic influenza A/H1N1 2009 virus, no difference in disease duration, median age, red blood cell count, hemoglobin concentration, C reactive protein concentration, and absolute neutrophil count was observed, whereas significant differences were apparent when considering WBC count, relative and absolute lymphocyte count, absolute lymphocyte count z‐score, and platelet count. Receiver operating characteristic curve analysis revealed that the best absolute lymphocyte count and absolute lymphocyte count z‐score cut‐points that simultaneously maximized sensitivity and specificity were 2,256 cells/µl and ?0.89, respectively, sensitivity being 0.81 (95% CI: 0.68–0.94), specificity 0.87 (95% CI: 0.77–0.98), positive predictive value 0.85 (95% CI: 0.74–0.97), and negative predictive value 0.83 (95% CI: 0.71–0.94). In conclusion, lymphocytopenia is a marker for influenza A/H1N1 2009 virus infection in children. Absolute lymphocyte count <2,556 cells/µl or absolute lymphocyte count z‐score < ?0.89 may be useful cut‐offs to discriminate against children at higher risk of infection during epidemics. Considering that the pandemic virus is highly likely to continue to circulate in the coming winter season, these findings provide direct and practical implications for the near future. J. Med. Virol. 83:1–4, 2011. © 2010 Wiley‐Liss, Inc.     

CDK1 Hyperphosphorylation Maintenance Drives the Time-course of G2-M Cell Cycle Arrest after Short Treatment with NAMI-A in Kb Cells

We investigated the molecular events of the ruthenium complex NAMI-A (0.1 mM for 1 h) on cell cycle G2-M arrest in KB carcinoma cells. Flow cytometry analysis showed a progressive accumulation of cells in S phase at 16 h, and in G2-M phase at 20 h after the end of treatment. NAMI-A pre-mitotic stop to cell proliferation was due to the maintenance of the phosphorylated, inactive, form of Cdk1, caused by the activation of the ATM/ATR checkpoint, as confirmed by the up-regulation and phosphorylation of Chk1. All these events are related to intracellular ruthenium accumulation, as confirmed by the lack of similar effects in cell lines unable to take the ruthenium compound up. Considering the dependence of NAMI-A cell cycle arrest on the dose and on the length of cell challenge, and considering the prolonged NAMI-A t1/2 in vivo in the lungs, we proved an even greater perturbation of the cell cycle regulating pathways in lung metastases of NAMI-A treated mice. The ex-vivo data confirm the interaction of the ruthenium compound NAMI-A with the ATM/ATR pathway, leading to the modulation of cell cycle regulating proteins, that can break the metastases cell cycle progression off.     

Unique vascular tumor primary arising in the liver and exhibiting histopathological features consistent with so‐called polymorphous hemangioendothelioma

Reported herein is an unusual vascular tumor primary arising in the liver and exhibiting unique histopathological features. A 47‐year‐old woman underwent left hepatectomy because of a large hepatic mass. On histology the tumor had a composite pattern, consisting of angiomatous, retiform and solid areas, formed by oval to cuboidal to spindle cells, that expressed only endothelial markers (CD31 and factor VIII‐related antigen). These findings led to the diagnosis of a low‐grade vascular neoplasm with morphological features consistent with so‐called polymorphous hemangioendothelioma. The tumor was completely resected. At 24 month follow up the patient was alive, without evidence of disease. Polymorphous hemangioendothelioma is a rare vascular neoplasm, with borderline malignant potential, which usually occurs in lymph nodes and, rarely, at extranodal sites. Its classification as an entity has been questioned recently. The unusual morphological features of the present case, which do not fit neatly with any other recognized hemangioendothelioma subtype, indicate that the family of vascular tumors is broader than currently accepted. In addition the present case widens the spectrum of primary vascular tumors arising in the liver.     

Controversies and Concerns in Hemodialysis Series Editor: Marcello Tonelli: What’s Next After Fistula First: Is an Arteriovenous Graft or Central Venous Catheter Preferable When an Arteriovenous Fistula Is Not Possible?

Findings from observational studies have established that the arteriovenous fistula (AVF) is the preferred form of vascular access for chronic hemodialysis. Unfortunately, in a subset of patients with end-stage renal disease, an AVF cannot be placed or fails to mature. In these patients an alternate form of vascular access, either an arteriovenous graft (AVG) or central venous catheter (CVC) must be selected. In this review we discuss the findings and limitations of studies examining the effect of access type (AVG or CVC) on clinical endpoints including mortality, quality of life, occurrence of infections, as well as the impact of the different access types on resource requirements. Specifically, we examine whether findings from previous studies are valid and applicable to patients for whom an AVF is not possible, and outline the need for future randomized clinical trials addressing this question.