Imaging the dynamics of the auditory steady-state evoked response

This study used magnetoencephalography (MEG) to examine the dynamic patterns of neural activity underlying the auditory steady-state response. We examined the continuous time-series of responses to a 32-Hz amplitude modulation. Fluctuations in the amplitude of the evoked response were found to be mediated by non-linear interactions with oscillatory processes both at the same source, in the alpha and beta frequency bands, and in the opposite hemisphere.     

Assessment and management of patients with leg ulcers

This article discusses the assessment and management of patients with leg ulcers, focusing on venous, arterial and mixed aetiology ulcers. Successful care planning should be based on working in partnership with patients in terms of offering choices that meet their clinical, quality-of-life and psychosocial needs.     

Observations of HRP labeling following injection through a chronically implanted cannula — A method to avoid diffusion of HRP into injured fibers

One of the limitations of the horseradish peroxidase (HRP) tracer method is the diffusion of HRP into injured axons resulting in unintended labeling of neurons not terminating in the injection area. To overcome this limitation, an experiment was designed to inject the HRP through an implanted cannula after degeneration and healing had taken place. It was shown that implantation of a cannula into the internal capsule significantly decreased the number of labeled axons in the injection site, thus limiting the unintended labeling of neurons from that injection. When injections followed implantation of the cannula by 24 h or more, fibers damaged by the cannula had healed or degenerated sufficiently that intraaxonal diffusion of HRP into those injured fibers did not occur. A significant difference between control (without the cannula) and experimental (with the cannula) injections was observed. Extensive axonal and neuronal labeling following the control injections was seen at the injection site and caudate nucleus, and in the thalamus and parietal cortex, respectively. Experimental injections resulted in sparse axonal and neuronal labeling evident mostly with the larger injections of HRP.     

Diacylglycerol-containing docosahexaenoic acid in acyl chain modulates airway smooth muscle tone

We synthesized and assessed the role of a diacylglycerol (DAG)-containing docosahexaenoic acid (DHA), that is, 1-stearoyl-2-docosahexaenoyl-sn-glycerol (SDHG), in the contraction of guinea pig airway smooth muscle (ASM). We compared its action with 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG) and 1,2-dioctanoyl-sn-glycerol (1,2-DiC8), a stable DAG analog. The three DAGs (SAG, SDHG, and 1,2-DiC8) induced reversible concentration-dependent contraction of ASM. SDHG induced higher guinea pig ASM contraction than did SAG and 1,2-DiC8. The effects of SDHG were blocked, to different extents, by nifedipine (L-type Ca2+ channel blocker). By employing GF-109203X (protein kinase C [PKC] inhibitor) and lanthanum (La3+), a nonselective cation channel blocker, we observed that SDHG evoked ASM contractile response via PKC-dependent and PKC-independent (but Ca2+-dependent) pathways. Interestingly, SAG exerted its action only by increasing [Ca2+]i and did not require PKC activation. To probe the implication of calcium mobilization, we employed thapsigargin (TG), which also induced ASM contraction in a calcium-dependent manner. SDHG and 1,2-DiC8, in a PKC-dependent manner, induced the phosphorylation of CPI-17 (myosin light chain phosphatase inhibitor of 17 kD). Furthermore, SAG and TG failed to phosphorylate CPI-17 in ASM cells. Our results suggest that different DAG species, produced during a dietary supplementation with fatty acids, could modulate the reactivity of airway smooth muscles in a PKC-dependent and -independent manner, and hence, may play a critical role in health and disease.     

Examination of the clock gene Cryptochrome 1 in bipolar disorder: mutational analysis and absence of evidence for linkage or association

Bipolar disorder is associated with malfunctions of the circadian system, which regulates individual circadian rhythms and which enables the adaptation to a daily 24-h cycle and seasonal change. One of the human circadian clock genes, cryptochrome 1 (Cry1) (located on 12q23-q24.1) was analyzed because of its close correspondence to a linkage hotspot for bipolar disorder.We found no evidence for linkage of 52 bipolar families to two Cry1 flanking microsatellites under several parametric and non-parametric models. In order to employ association for a more sensitive test, 25 affected subjects selected from families with positive LOD scores were screened for mutations by sequencing 9.5% of the Cry1 gene. A total of 16 single nucleotide polymorphisms (SNPs) and a 3 base pair insertion were identified. However, no mutations with probable functional impact were found. These novel SNPs and data on allele frequency and linkage disequilibrium structure will be useful for future association analyses. Nine SNPs have been analyzed in a set of 159 parent proband triads. Linkage disequilibrium analyses using single SNPs and haplotypes showed no association to bipolar disease.Additional, more powerful, studies involving Cry1 and other circadian clock genes need to be tested before an association of circadian abnormalities with bipolar disorder can be excluded.     

AKT activation predicts outcome in breast cancer patients treated with tamoxifen

Oestrogen receptor (ERalpha) expression is a strong predictor of response to endocrine therapy. The PI3K/AKT/mTOR signal transduction pathway has been implicated in endocrine resistance in vitro. The present study was carried out to test the hypothesis that AKT activation mediates tamoxifen resistance in clinical breast cancer. Immunohistochemistry (IHC) using AKT1-3, pan-AKT, pAKT (Thr-308), pAKT (Ser-473), pER (Ser-167), and pHER2 antibodies was performed on 402 ERalpha-positive breast carcinomas from patients treated with tamoxifen. High pAKT (Ser-473) activity (p = 0.0406) and low AKT2 expression (p = 0.0115) alone, or in combination [high pAKT (Ser-473)/low AKT2; 'high-risk' patient group] (p = 0.0014), predicted decreased overall survival in tamoxifen-treated patients with ERalpha-positive breast cancers. There was no significant association between tumour levels of AKT expression or activity and disease-free survival (DFS); however, the 'high-risk' patient group was significantly more likely to relapse (p = 0.0491). During tamoxifen treatment, neither AKT2 nor pAKT predicted DFS. Finally, activation of AKT, via phosphorylation, was linked to activation of both HER2 and ERalpha in this patient cohort. The data presented here show that the PI3K/AKT/mTOR pathway is associated with relapse and death in ERalpha-positive breast cancer patients treated with tamoxifen, supporting in vitro evidence that AKT mediates tamoxifen resistance. Patients with a 'high-risk' expression profile were at increased risk of death (hazard ratio 3.22, p = 0.002) relative to 'low-risk' patients, highlighting the potential that tumour profiling, with multiple IHC markers predictive of therapeutic response, may improve patient selection for endocrine therapies, eg tamoxifen or aromatase inhibitor-based treatments.     

Personality factors and disordered eating in young women with type 1 diabetes mellitus

The authors examined the association between the presence of personality variables implicated in the pathogenesis of eating disorders and the presence of eating disorder symptoms in 51 women with type 1 diabetes. Subjects were assessed with interview instruments and self-report questionnaires, including scales measuring eating disorder symptoms, borderline personality characteristics, and perfectionism. Fourteen subjects displayed moderate to severe eating disorder symptoms. Perfectionism was related to attitudinal aspects of eating disorders (e.g., weight preoccupation), and borderline personality characteristics were related to disordered behaviors (e.g., insulin omission) and poor glycemic control. The results suggest that personality factors are related to disordered eating and poor glycemic control in diabetic women.