The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.     

Intracranial mycotic aneurysm due to Aspergillus species.

BACKGROUND: Intracranial true mycotic aneurysms are uncommon and usually fatal. We report two patients with basilar mycotic aneurysms due to Aspergillus species following surgical interventions. Both patients had subarachnoid hemorrhage and diagnosis was made at autopsy only. The literature regarding etiology, clinical presentation, predisposing conditions and outcome of intracranial true mycotic aneurysms is reviewed from 1990-2005. A high index of clinical suspicion with prompt diagnosis and early treatment may improve patient outcome.     

Regional Variation and Use of Exception Letters for Cadaveric Liver Allocation in Children with Chronic Liver Disease

The Pediatric End-Stage Liver Disease (PELD) score was designed to reduce subjectivity in liver allocation and to advantage patients with a higher probability of waiting list mortality. The aims of this study were to determine the impact of PELD implementation for children with chronic liver disease and to assess whether PELD met its goal of standardization of liver allocation for children. This study used data reported to the United Network for Organ Sharing (UNOS) registry for children with chronic liver disease receiving primary cadaveric liver transplant between January 2000 and December 2001 (pre-PELD) and March 2002 and July 2003 (PELD). PELD reduced the percentage of children transplanted while in an intensive care unit and as status 1. A calculated PELD score was used for allocation in only 52% of recipients. Thirty percent were status 1 at transplant and PELD scores granted by exception were used for allocation in 18% of patients. There was regional variation in PELD score at allocation and use of exception scores with a significant relationship between PELD score and percentage of exception cases. Regional variation suggests that PELD has not resulted in standardization of listing practices in pediatric liver transplantation.     

Intractable Diarrhea from Carbamazepine

Diarrhea has been reported as an early, mild, and uncommon complication of carbamazepine (CBZ) therapy. We report three cases of intractable diarrhea induced by CBZ necessitating discontinuation of the drug.     

Single-trial evoked potential estimation: comparison between independent component analysis and wavelet denoising.

OBJECTIVE: Brain responses to repeated sensory stimuli are typically buried in the more prominent background activity, and thus analysis of these responses on a single-trial basis would require advanced procedures to estimate the brain activity related only to the experimental task. Recently, we have proposed a new iterative independent component analysis (iICA) approach to estimate single-trial responses. In this paper, we compare the performance of iICA at estimating single-trial responses with ensemble averaging and wavelet transform (WT) denoising. METHODS: We analyzed simulated evoked potentials (EPs) and actual recordings of the auditory N100 component from 33 normal subjects, and the performance of each method was quantified in terms of the average root-mean-square error and average correlation before and after processing. RESULTS: We found that WT gave a smoother overall average EP, while iICA could isolate the N100 component out of the entire EP waveform. With simulated data, iICA provided significantly better estimates of the true EP compared to plain averaging (p<0.01) and WT (p<0.01). With actual data, iICA showed clear responses in single trials, in all subjects. Additionally, the corresponding average EPs had a sharper N100-P200 complex, with flatter preceding and following regions, resulting in an enhanced N100 component. CONCLUSIONS: The iICA procedure can provide clear responses in each single trial, and the resulting average N100 component is significantly improved compared to plain averaging and wavelet denoising. SIGNIFICANCE: The proposed technique may have a significant impact as a clinical tool in the analysis of single-trial responses.     

Cardiac injuries--a clinical and autopsy profile

One hundred two patients sustaining cardiac injuries over a 4-year period were analysed to highlight the natural history of the cardiac injuries. There were 45 blunt, 36 stab, and 21 gunshot injuries. The injury involved the ventricle in 85, atrium in seven, pulmonary artery in five cases, and resulted in crush injury to the heart in the remaining five cases. Thirty-three patients (32.3%) died on the scene and 58 (56.9%) died during the transportation. Only 11 patients (10.8%) reached the hospital alive, and ten of these patients survived following thoracotomy and repair of the cardiac injury. The factors influencing the natural course of cardiac injury were analysed: 2.2% of patients with blunt cardiac trauma reached the hospital alive compared to 19.4% with stab and 14.3% with gunshot injuries; ventricular injuries had a greater prehospital mortality compared to atrial or pulmonary artery injuries; 11.3% of patients sustaining injury to right ventricle reached the hospital alive compared to 3% of those with left ventricular injuries. These data emphasize the need for rapid transport, immediate recognition, and aggressive surgical management, to make a favourable impact on the natural history of cardiac injuries.     

Cysteine Conjugate beta-Lyase-Dependent Metabolism of Compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene) in Human Subjects Anesthetized with Sevoflurane and in Rats Given Compound A

Background: Sevoflurane undergoes Baralyme- or soda lime-catalyzed degradation in the anesthesia circuit to yield compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene), which is nephrotoxic in rats and undergoes metabolism via the cysteine conjugate beta-lyase pathway in those animals. The objective of these experiments was to test the hypothesis that compound A undergoes beta-lyase-dependent metabolism in humans.

Methods: Human volunteers were anesthetized with sevoflurane (1.25 minimum alveolar concentration, 3%, 2 l/min, 8 h) and thereby exposed to compound A. Urine was collected at 24-h intervals for 72 h after anesthesia. Rats, which served as a positive control, were given compound A intraperitoneally, and urine was collected for 24 h afterward. Human and rat urine samples were analyzed by19 F nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry for the presence of compound A metabolites.

Results: Analysis of human and rat urine showed the presence of the compound A metabolites [S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-N-acetyl-L-cysteine, (E)- and (Z)-S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-N-acetyl-L-cyst eine, 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid, 3,3,3-trifluorolactic acid, and inorganic fluoride. The presence of 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid in human urine was confirmed by gas chromatography-mass spectrometry.     

Isolation of DNA from the centromere of human chromosome 7 by microdissection

Centromeres remain the least characterized regions of human chromosomes because they have a very high content of repetitive DNA. Here, we describe a micro-dissection library from the centromeric region of human chromosome 7 and its use for generating sequence tagged sites (STSs). The library contains about 1500 clones with an average insert size of 150 bp and only about 15% of the clones harbour repetitive human DNA. Seven clones hybridizing to alphoid DNA were found to correspond to a fragment of the D7Z2 alphoid array on chromosome 7, thus confirming the origin of the library. A number of clones not containing known repetitive DNA were used to generate STSs that identified yeast artificial chromosomes (YACs) and in turn allowed the STSs to be placed on the physical map. One STS is located between the two Genethon genetic markers closest to the centromere on the q side. Another STS was located 3–4 cM away in 7q11.2, while a third identified YACs containing both low-copy and alphoid sequences that are not yet mapped but are clearly centromeric. The library therefore comprises a collection of sequences from the centromeric region of chromosome 7 that can be used to generate STSs and to map the entire centromeric region.This revised version was published online in November 2005 with corrections to the Cover Date.