Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy.

Northern hybridization analyses of the oestrogen-inducible mRNAs pLIV1 and pS2 were compared with oestrogen receptor (ER) immunocytochemistry assessments in 40 untreated primary or early recurrent breast tumours. Significant associations were observed between pLIV1/ER (P < 0.03), pS2/ER (P < 0.001) and pLIV1/pS2 (P < 0.04) status. After disease recurrence, patients were treated with assessable courses of endocrine therapies. Positive pLIV1, pS2 and ER statuses in primary disease were consequently found to be predictive of endocrine responsiveness in the secondary lesions (P < 0.03, P < 0.02, P < 0.005 respectively). However, despite these associations, a number of pLIV1- and/or pS2-positive tumours failed to respond to therapy.     

Botulinum toxin for cerebral palsy; where are we now?

In this article, the evidence base for botulinum-A treatment acquired in recent years is outlined, and the practicalities involved in providing this service are described. Botulinum-A is relatively new, and possible improvements for the future are considered.     

Calcium binding proteins in motoneurons at low and high risk for degeneration in ALS

Recent reports challenge the hypothesis that expression of calcium binding proteins contributes to the greater resistance of some motoneurons to degeneration in amyotrophic lateral sclerosis (ALS). We therefore re-examined, using immunohistochemistry, the expression of calbindin, calretinin and parvalbumin in vulnerable (hypoglossal, XII; and cervical spinal) and resistant (oculomotor, III) motoneurons of adult rats. Calbindin immunoreactivity was lacking in motor nuclei but strong in the dorsal horn. Calretinin was expressed in spinal, but not III or XII, motoneurons. Parvalbumin immunoreactivity, tested with a polyclonal antibody, was intense in spinal and III, but not XII, motoneurons; however, no staining in the ventral horn was observed with a monoclonal antibody. Differential expression of calretinin and parvalbumin within vulnerable motoneurons suggests that immunoreactivity for these proteins is not a reliable marker for resistance to degeneration in ALS.     

Detection of mono- and di-hexoses as metabolites of 4-bromoaniline using HPLC-TOF-MS/MS

1. The metabolic fate of 4-bromoaniline (4-BrA) was investigated in rat following intraperitoneal administration at 50?mg kg ? 1 using HPLC-TOF-MS/MS. 2. The sensitivity provided by the use of TOF-MS/MS, aided by the distinctive isotope pattern resulting from the presence of the bromine substituent in the molecule, enabled the detection of many previously uncharacterized metabolites in the samples. 3. Several groups of minor metabolites were detected in the urine that corresponded to a number of isomeric hexose and di-hexose-containing conjugates (possibly glucosides and diglucosides) of 4-BrA. 4. As well as hexose and di-hexose conjugates of 4-BrA, several further groups of metabolites that also contained either a sulphamate or sulphate group in addition to the sugar moieties were also detected.     

Relative neuroprotective effects hyperbaric oxygen treatment and TLR4 knockout in a mouse model of temporary middle cerebral artery occlusion

Purpose: To examine the effects of hyperbaric oxygen (HBO) therapy and knockout of toll-like receptor 4 (TLR4) on the outcome of temporary middle cerebral artery occlusion (MCAO) in a mouse model. Materials and Methods: MCAO was induced in anesthetized male C57Bl/6 mice (WT) and TLR4 knockout mice (TLR4^?/?) using an intra-arterial filament method. After 30 or 90 min, the filament was removed, and the mice were given either no treatment (WT and TLR4^?/- groups) or HBO (WT only). Mice were euthanized 24 h after MCAO, and the brain infarct area was examined using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Results: In the WT group, without treatment, lesion volume was 120 ± 13 mm³ in the mice subjected to 30 min’ MCAO and 173 ± 23 mm³ in the mice subjected to 90 min’ MCAO. Respective values with HBO treatment were 66.5 ± 36.7 mm³ and 53.2 ± 17.2 mm³. The difference was significant only for 90-minute MCAO (p < 0.01, nonparametric test). In the TLR4^?/? group (all untreated), lesion volume was 95.9 ± 17.9 after 90 min of MCAO, which was significantly lower than in the untreated WT animals (p < 0.05, nonparametric test). Conclusions: A single treatment of HBO immediately after MCAO followed by 24 h’ reperfusion significantly reduces edema and may improve perfusion. TLR4 knockout protects mice from MCAO damage, but to a lesser extent than HBO treatment.