GPX-Macrophage Expression Atlas: a database for expression profiles of macrophages challenged with a variety of pro-inflammatory, anti-inflammatory, benign and pathogen insults.

BACKGROUND: Macrophages play an integral role in the host immune system, bridging innate and adaptive immunity. As such, they are finely attuned to extracellular and intracellular stimuli and respond by rapidly initiating multiple signalling cascades with diverse effector functions. The macrophage cell is therefore an experimentally and clinically amenable biological system for the mapping of biological pathways. The goal of the macrophage expression atlas is to systematically investigate the pathway biology and interaction network of macrophages challenged with a variety of insults, in particular via infection and activation with key inflammatory mediators. As an important first step towards this we present a single searchable database resource containing high-throughput macrophage gene expression studies. DESCRIPTION: The GPX Macrophage Expression Atlas (GPX-MEA) is an online resource for gene expression based studies of a range of macrophage cell types following treatment with pathogens and immune modulators. GPX-MEA follows the MIAME standard and includes an objective quality score with each experiment. It places special emphasis on rigorously capturing the experimental design and enables the searching of expression data from different microarray experiments. Studies may be queried on the basis of experimental parameters, sample information and quality assessment score. The ability to compare the expression values of individual genes across multiple experiments is provided. In addition, the database offers access to experimental annotation and analysis files and includes experiments and raw data previously unavailable to the research community. CONCLUSION: GPX-MEA is the first example of a quality scored gene expression database focussed on a macrophage cellular system that allows efficient identification of transcriptional patterns. The resource will provide novel insights into the phenotypic response of macrophages to a variety of benign, inflammatory, and pathogen insults. GPX-MEA is available through the GPX website at http://www.gti.ed.ac.uk/GPX.

Acute Onset of Guillain-Barré Syndrome After Elective Spinal Surgery.

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy caused by an autoimmune response against myelin of peripheral nerves. GBS has been reported after surgery, in general, and after spinal surgery, in particular. In most cases, GBS developed 1-3 weeks after surgery. METHODS: Report of 2 cases of GBS after elective spine surgery that developed in the immediate postoperative period. RESULTS: Within 1 and 3 hours after surgery, respectively, both patients developed ascending loss of motor and sensory function. They were taken back urgently to the operating room for wound exploration to ensure that an epidural hematoma had not developed. Cerebrospinal fluid studies and electromyography/nerve conduction velocity were then rapidly obtained and were compatible with acute inflammatory demyelinating polyradiculoneuropathy. Therapy was initiated with administration of intravenous immunoglobulin and plasmapheresis. Both patients made substantial motor recovery during the course of 1-2 years but have residual sensory abnormalities. CONCLUSIONS: GBS developing acutely after spinal surgery is a rare occurrence but should be considered in the differential diagnosis of neurological deterioration after surgery. Rapid diagnosis and treatment are essential for recovery of neurological function.

Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug.

The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P(+)-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

Hemangioblastoma of the optic nerve producing bilateral optic tract edema in a patient with von Hippel-Lindau disease.

BACKGROUND: The authors present a novel case of a hemangioblastoma of the optic nerve producing bilateral optic tract edema in a patient with von Hippel-Lindau disease (VHL). This is the only case in the literature documenting optic tract edema secondary to a hemangioblastoma of the optic nerve. CASE DESCRIPTION: The patient was a 34-year-old female in whom this lesion was causing retro-orbital pain and proptosis. She had previously lost vision in the symptomatic eye secondary to a retinal hemangioblastoma. The optic nerve lesion was excised by sectioning the optic nerve both proximally and distally to the lesion. There were no complications and patient's symptoms resolved postoperatively. A follow-up magnetic resonance imaging (MRI) scan revealed complete excision of the mass and resolution of the optic tract edema. CONCLUSION: Optic nerve hemangioblastomas in patients with VHL are rare, but are manageable with meticulous microneurosurgery and with appropriate patient expectations. This is the first known case of an optic nerve hemangioblastoma producing bilateral optic tract edema, which resolved after resection of the prechiasmal tumor. Hemangioblastoma should remain in the differential diagnosis of optic nerve tumors, especially in the setting of VHL.

Sacral radiculopathy due to cement leakage from percutaneous sacroplasty, successfully treated with surgical decompression.

Percutaneous sacroplasty is a procedure adapted from vertebroplasty, which is designed to ameliorate the painful morbidity associated with sacral insufficiency fractures without the invasiveness of open surgery. Early estimates of efficacy, according to several case reports and small series, appear promising, but the procedure is not without risk. Several cases of radiculopathy due to nerve root compression by extravasated polymethylmethacrylate (PMMA) have been reported. The authors present a case of radiculopathy caused by cement leakage from sacroplasty, treated with surgical decompression of the compromised nerve root. The patient presented with left S-1 radiculopathy and was found on CT to have a left S-1 nerve root completely encased in PMMA over a portion of its length. The patient underwent sacral laminectomy with the removal of PMMA and experienced pain relief and the return of function postoperatively. Surgical removal of PMMA extravasated during sacroplasty is feasible and should be considered when nerve root compression or canal stenosis causes pain or neurological deficit refractory to conservative therapy.

Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA.

Thimerosal generates ethylmercury in aqueous solution and is widely used as preservative. We have investigated the toxicology of Thimerosal in normal human astrocytes, paying particular attention to mitochondrial function and the generation of specific oxidants. We find that ethylmercury not only inhibits mitochondrial respiration leading to a drop in the steady state membrane potential, but also concurrent with these phenomena increases the formation of superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated hydroxyl radical. These oxidants increase the levels of cellular aldehyde/ketones. Additionally, we find a five-fold increase in the levels of oxidant damaged mitochondrial DNA bases and increases in the levels of mtDNA nicks and blunt-ended breaks. Highly damaged mitochondria are characterized by having very low membrane potentials, increased superoxide/hydrogen peroxide production, and extensively damaged mtDNA and proteins. These mitochondria appear to have undergone a permeability transition, an observation supported by the five-fold increase in Caspase-3 activity observed after Thimerosal treatment.

Improved silicon nitride surfaces for next-generation microarrays.

This work reports how the use of a standard integrated circuit (IC) fabrication process can improve the potential of silicon nitride layers as substrates for microarray technology. It has been shown that chemical mechanical polishing (CMP) substantially improves the fluorescent intensity of positive control gene and test gene microarray spots on both low-pressure chemical vapor deposition (LPCVD) and plasma-enhanced chemical vapor deposition (PECVD) silicon nitride films, while maintaining a low fluorescent background. This results in the improved discrimination of low expressing genes. The results for the PECVD silicon nitride, which has been previously reported as unsuitable for microarray spotting, are particularly significant for future devices that hope to incorporate microelectronic control and analysis circuitry, due to the film's use as a final passivating layer.

Biochip sensors for the rapid and sensitive detection of viral disease.

Recent advances in DNA and protein microarray methodology and the emerging technology of cell-based sensors have massively increased the speed and sensitivity with which we can detect viral infections. The advantages of the multi-parameter microarray technologies could be combined with the speed and sensitivity of cell-based systems to give 'cell-omic' sensors.