Differences in global DNA methylation of testicular seminoma are not associated with changes in histone modifications, clinical prognosis, BRAF mutations or gene expression.

Testicular germ cell tumours of young adults are comprised of a heterogeneous group of non-seminomas and a homogeneous group of seminomas. While the majority of seminomas retain a hypo-methylated genome, a small fraction displays a highly methylated genome, resembling hyper-methylated non-seminomas. It is well established from e.

Vaccine Targeting of Subdominant CD8+ T Cell Epitopes Increases the Breadth of the T Cell Response upon Viral Challenge, but May Impair Immediate Virus Control.

As a result of the difficulties in making efficient vaccines against genetically unstable viruses such as HIV, it has been suggested that future vaccines should preferentially target subdominant epitopes, the idea being that this should allow a greater breadth of the induced T cell response and, hence, a greater efficiency in controlling escape variants. However, to our knowledge the evidence supporting this concept is limited at best. To improve upon this, we used the murine lymphocytic choriomeningitis virus model and adenoviral vectors to compare a vaccine expressing unmodified Ag to a vaccine expressing the same Ag without its immunodominant epitope.

Reaction to topical capsaicin in spinal cord injury patients with and without central pain.

Central neuropathic pain is a debilitating and frequent complication to spinal cord injury (SCI). Excitatory input from hyperexcitable cells around the injured grey matter zone is suggested to play a role for central neuropathic pain felt below the level of a spinal cord injury. Direct evidence for this hypothesis is difficult to obtain.

Amygdala GABA-A receptor involvement in mediating sensory-discriminative and affective-motivational pain responses in a rat model of peripheral nerve injury.

The contribution of the amygdala to neuropathic pain processing in animals has not been clearly acknowledged. To assess the relative contribution of amygdala GABA-A receptors in mediating sensory-discriminative and affective-motivational pain components, the GABA-A receptor agonist muscimol and the antagonist bicuculline (both 10-25 ng/microl) were administered by acute bilateral injection directly into the central amygdala in rats with a chronic constriction injury (CCI). Escape/avoidance behaviour reflecting the affective-motivational dimension of pain was measured using a light/dark chamber in combination with suprathreshold nociceptive stimulation, and was defined as a shift from the 'non-aversive' dark area of the chamber to the 'aversive' light area.

Pharmacological characterisation of place escape/avoidance behaviour in the rat chronic constriction injury model of neuropathic pain.

Rationale: Classical pain tests performed in animals routinely measure evoked nociceptive behaviours. These almost exclusively reflect sensory processing of nociceptive transmission, although a recently described place escape/avoidance paradigm may be used to selectively assess affective pain processing.

Objective: To establish if drugs with proven analgesic efficacy selectively attenuate sensory-discriminative or affective-motivational aspects of nociceptive processing.

Anti-nociception is selectively enhanced by parallel inhibition of multiple subtypes of monoamine transporters in rat models of persistent and neuropathic pain.

Rationale: Neuropathic pain is characterised by hyperexcitability within nociceptive pathways that manifests behaviourally as allodynia and hyperalgesia and remains difficult to treat with standard analgesics. However, antidepressants have shown reasonable preclinical and clinical anti-nociceptive efficacy against signs and symptoms of neuropathic pain.

Objectives: To ascertain whether inhibition of serotonin (5-HT) and/or noradrenaline (NA) and/or dopamine (DA) re-uptake preferentially mediates superior anti-nociception in preclinical pain models.