Multimodal Temporal Pattern Discrimination Is Encoded in Visual Cortical Dynamics.

Discriminating between temporal features in sensory stimuli is critical to complex behavior and decision-making. However, how sensory cortical circuit mechanisms contribute to discrimination between subsecond temporal components in sensory events is unclear. To elucidate the mechanistic underpinnings of timing in primary visual cortex (V1), we recorded from V1 using two-photon calcium imaging in awake-behaving mice performing a go/no-go discrimination timing task, which was composed of patterns of subsecond audiovisual stimuli. In both conditions, activity during the early stimulus period was temporally coordinated with the preferred stimulus. However, while network activity increased in the preferred condition, network activity was increasingly suppressed in the nonpreferred condition over the stimulus period. Multiple levels of analyses suggest that discrimination between subsecond intervals that are contained in rhythmic patterns can be accomplished by local neural dynamics in V1.

Merkel cell carcinoma of the face: an analysis of 16 cases in the Japanese.

BACKGROUND: There is no agreement regarding a staging system and optimal treatment of Merkel cell carcinoma. Some centres have reported results from larger series of patients, but these do not include Asian or Japanese centres. OBJECTIVE: The purpose of this study was to retrospectively review our experience with the surgical treatment of MCC of the face in the Japanese and to study its management and outcome using the staging system described by Clark et al. METHODS: We report our experiences with 16 cases between 1991 and 2004. Patients and tumour characteristics, treatment variables and outcome were analysed. RESULTS: The follow-up periods ranged from 1 to 180 months. The average was 32.6 months and the median was 17.5 months. The relapse-free survival for all patients was 51% at 2 years. The relapse-free survival was 80% for the patients with Stage I and 33% with Stage II at 2 years. CONCLUSION: This staging system was suggested to reflect prognosis although the number of patients in this series was small. Sentinel lymph node biopsy should be considered to determine the accurate nodal staging, and patients with MCC of the head and neck may be treated according to the revised staging system by Clark et al.

Simvastatin inhibits growth via apoptosis and the induction of cell cycle arrest in human melanoma cells.

Competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (the statins) that inhibit the synthesis of mevalonic acid are in wide use for treatment of hypercholesterolemia. Although antitumor effects on a variety of cell types have been reported for statins, the effect of simvastatin (one of the statins) on human melanoma cell lines is not known. Here, we report antitumor effects of simvastatin on human melanoma cell lines. We treated human melanoma cell lines, A375M, G361, C8161, GAK, and MMAc with simvastatin in various concentrations for 1 to 3 days. To investigate the antitumor effect of simvastatin, we analyzed cell viability, morphologic changes, reversibility of inhibition by geranylgeranyl pyrophosphate and farnesyl pyrophosphate, apoptosis and the cell cycle. Simvastatin treatment reduced cell viability in all five melanoma cell lines. The different melanoma cell lines, however, displayed different sensitivities to simvastatin. The addition of geranylgeranyl pyrophosphate to A375M and G361 cells in the presence of simvastatin completely restored the viability of cells, but the addition of farnesyl pyrophosphate did not. DNA fragmentation assay showed that simvastatin induced apoptosis in A375M and G361 cells. Simvastatin caused a G1 arrest in G361 and MMAc cells. Consistent with the cell cycle arrest, simvastatin caused an increase in the mRNA levels of p21 and p27 on G361 and MMAc cells. We conclude that simvastatin has an antitumor effect on human melanoma cells in vitro via apoptosis and cell cycle arrest. These results suggest that simvastatin may be an effective anticancer drug for malignant melanoma.

Double innervation occurs in the facial mimetic muscles after facial-hypoglossal end-to-side neural repair: rat model for neural supercharge concept.

BACKGROUND: Double innervation of facial mimetic muscles by both facial and hypoglossal nerves after end-to-side neurorrhaphy has not been proven, although facial -hypoglossal end-to-side neurorrhaphy has been used in persistent incomplete facial palsy recently, and has achieved clinical evidences of recovery with rare synkinesis. We established a rat model to compare synkinesis after end-to-end and end-to-side neurorrhaphy techniques between facial and hypoglossal nerves, and confirmed double innervation using retrograde tracers. METHODS: Rats were divided into three groups (each consisting of six rats), a facial palsy group (Group A), a facial-hypoglossal end-to-end neurorrhaphy group (Group B), and a facial-hypoglossal end-to-side neurorrhaphy group (Group C). Eight weeks after surgery, synkinesis of the facial mimetic muscles was observed and recorded via video camera. In Group C, post operative, intramuscular injections of retrograde neural tracers (Fast Blue, Diamidino Yellow and DiI) into the facial mimetic muscles were performed to prove double innervation by both the facial and hypoglossal nerves. RESULTS: In Group B, all rats showed facial palsy. However while eating and drinking, their half of the face showed mass movements (strong contraction of whisker pad muscles, curved nose and eye-closure). In Group C, four rats showed no significant changes however, two rats showed synkinesis of the eyelid while eating and drinking (frequent eye-closure distinguishable from the contralateral normal side). In Group C, retrograde tracers injected in the mimetic muscles were detected in both the facial and hypoglossal motor nuclei in situ of all the rats' brain stem. CONCLUSION: This study proved that double innervation of mimetic muscles by both facial and hypoglossal nerves occurs after the end-to-side neurorrhaphy. Double-innervated mimetic muscles around the mouth after hypoglossal-facial end-to-side neurorrhaphy showed less synkinesis than the end-to-end neurorrhaphy.

Evaluation of the sclerotherapeutic efficacy of ethanol, polidocanol, and OK-432 using an in vitro model.

BACKGROUND: Sclerosants are used to treat vascular malformations. Owing to variations in the flow, the injected concentrations and the duration of exposure of these sclerosants are altered. Therefore, the clinical effectiveness of sclerotherapy is variable. OBJECTIVE: The objective was to evaluate the differences in clinical response, usually observed among ethanol, polidocanol, and OK-432, using an in vitro sclerotherapy model. METHODS: Endothelial cells were cultured and exposed to different concentrations of the sclerosants for 5 seconds and the remaining viable cells were counted using a MTT assay kit. Dyes were used to visualize the morphologic changes. Precipitant formation in blood was also evaluated. Finally, the degree of ICAM-1 expression, after exposure to lower concentrations of these sclerosants, was studied using immunocytochemistry. RESULTS: Only ethanol causes precipitant formation and kills almost all cells from 30% concentration. Polidocanol begins to disrupt the cell membrane from 0.0125% onward. Only OK-432 induces ICAM-1 expression. CONCLUSION: Ethanol's strong precipitant-forming effect may induce thromboembolism, thus enhancing sclerosis. Polidocanol's endothelial cell-lysing effect was clearly documented. OK-432 may mediate its effect by inducing inflammatory response of the endothelium via ICAM-1 expression. This in vitro model may be useful in evaluating other sclerosants as well.