Neuronal activity in medial superior temporal area (MST) during memory-based smooth pursuit eye movements in monkeys

We examined recently neuronal substrates for predictive pursuit using a memory-based smooth pursuit task that distinguishes the discharge related to memory of visual motion-direction from that related to movement preparation. We found that the supplementary eye fields (SEF) contain separate signals coding memory and assessment of visual motion-direction, decision not-to-pursue, and preparation for pursuit. Since medial superior temporal area (MST) is essential for visual motion processing and projects to SEF, we examined whether MST carried similar signals. We analyzed the discharge of 108 MSTd neurons responding to visual motion stimuli. The majority (69/108 = 64%) were also modulated during smooth pursuit. However, in nearly all (104/108 = 96%) of the MSTd neurons tested, there was no significant discharge modulation during the delay periods that required memory of visual motion-direction or preparation for smooth pursuit or not-to-pursue. Only 4 neurons of the 108 (4%) exhibited significantly higher discharge rates during the delay periods; however, their responses were non-directional and not instruction specific. Representative signals in the MSTd clearly differed from those in the SEF during memory-based smooth pursuit. MSTd neurons are unlikely to provide signals for memory of visual motion-direction or preparation for smooth pursuit eye movements

Effective in vivo and ex vivo gene transfer to intestinal mucosa by VSV-G-pseudotyped lentiviral vectors

<p>Abstract</p> <p>Background</p> <p>Gene transfer to the gastrointestinal (GI) mucosa is a therapeutic strategy which could prove particularly advantageous for treatment of various hereditary and acquired intestinal disorders, including inflammatory bowel disease (IBD), GI infections, and cancer.</p> <p>Methods</p> <p>We evaluated vesicular stomatitis virus glycoprotein envelope (VSV-G)-pseudotyped lentiviral vectors (LV) for efficacy of gene transfer to both murine rectosigmoid colon <it>in vivo </it>and human colon explants <it>ex vivo</it>. LV encoding beta-galactosidase (LV-β-Gal) or firefly-luciferase (LV-fLuc) reporter genes were administered by intrarectal instillation in mice, or applied topically for <it>ex vivo </it>transduction of human colorectal explant tissues from normal individuals. Macroscopic and histological evaluations were performed to assess any tissue damage or inflammation. Transduction efficiency and systemic biodistribution were evaluated by real-time quantitative PCR. LV-fLuc expression was evaluated by <it>ex vivo </it>bioluminescence imaging. LV-β-Gal expression and identity of transduced cell types were examined by histochemical and immunofluorescence staining.</p> <p>Results</p> <p>Imaging studies showed positive fLuc signals in murine distal colon; β-Gal-positive cells were found in both murine and human intestinal tissue. In the murine model, β-Gal-positive epithelial and lamina propria cells were found to express cytokeratin, CD45, and CD4. LV-transduced β-Gal-positive cells were also seen in human colorectal explants, consisting mainly of CD45, CD4, and CD11c-positive cells confined to the LP.</p> <p>Conclusions</p> <p>We have demonstrated the feasibility of LV-mediated gene transfer into colonic mucosa. We also identified differential patterns of mucosal gene transfer dependent on whether murine or human tissue was used. Within the limitations of the study, the LV did not appear to induce mucosal damage and were not distributed beyond the distal colon.</p

Transcriptional Changes Common to Human Cocaine, Cannabis and Phencyclidine Abuse

A major goal of drug abuse research is to identify and understand drug-induced changes in brain function that are common to many or all drugs of abuse. As these may underlie drug dependence and addiction, the purpose of the present study was to examine if different drugs of abuse effect changes in gene expression that converge in common molecular pathways. Microarray analysis was employed to assay brain gene expression in postmortem anterior prefrontal cortex (aPFC) from 42 human cocaine, cannabis and/or phencyclidine abuse cases and 30 control cases, which were characterized by toxicology and drug abuse history. Common transcriptional changes were demonstrated for a majority of drug abuse cases (N = 34), representing a number of consistently changed functional classes: Calmodulin-related transcripts (CALM1, CALM2, CAMK2B) were decreased, while transcripts related to cholesterol biosynthesis and trafficking (FDFT1, APOL2, SCARB1), and Golgi/endoplasmic reticulum (ER) functions (SEMA3B, GCC1) were all increased. Quantitative PCR validated decreases in calmodulin 2 (CALM2) mRNA and increases in apolipoprotein L, 2 (APOL2) and semaphorin 3B (SEMA3B) mRNA for individual cases. A comparison between control cases with and without cardiovascular disease and elevated body mass index indicated that these changes were not due to general cellular and metabolic stress, but appeared specific to the use of drugs. Therefore, humans who abused cocaine, cannabis and/or phencyclidine share a decrease in transcription of calmodulin-related genes and increased transcription related to lipid/cholesterol and Golgi/ER function. These changes represent common molecular features of drug abuse, which may underlie changes in synaptic function and plasticity that could have important ramifications for decision-making capabilities in drug abusers

Altered Velocity Processing in Schizophrenia during Pursuit Eye Tracking

Smooth pursuit eye movements (SPEM) are needed to keep the retinal image of slowly moving objects within the fovea. Depending on the task, about 50%–80% of patients with schizophrenia have difficulties in maintaining SPEM. We designed a study that comprised different target velocities as well as testing for internal (extraretinal) guidance of SPEM in the absence of a visual target. We applied event-related fMRI by presenting four velocities (5, 10, 15, 20°/s) both with and without intervals of target blanking. 17 patients and 16 healthy participants were included. Eye movements were registered during scanning sessions. Statistical analysis included mixed ANOVAs and regression analyses of the target velocity on the Blood Oxygen Level Dependency (BOLD) signal. The main effect group and the interaction of velocity×group revealed reduced activation in V5 and putamen but increased activation of cerebellar regions in patients. Regression analysis showed that activation in supplementary eye field, putamen, and cerebellum was not correlated to target velocity in patients in contrast to controls. Furthermore, activation in V5 and in intraparietal sulcus (putative LIP) bilaterally was less strongly correlated to target velocity in patients than controls. Altered correlation of target velocity and neural activation in the cortical network supporting SPEM (V5, SEF, LIP, putamen) implies impaired transformation of the visual motion signal into an adequate motor command in patients. Cerebellar regions seem to be involved in compensatory mechanisms although cerebellar activity in patients was not related to target velocity

Suppression of metastatic cancer by N116Y

In pancreatic cancer, the mutation of c-K-ras is a critical event of tumor growth and metastasis.1 We have previously demonstrated a dominant negative effect of N116Y on the growth of pancreatic cancer cells.2 To evaluate the potential of N116Y for suppressing the metastatic growth of pancreatic tumor cells, we made a replication-deficient recombinant N116Y adenovirus driven by the carcinoembryonic antigen (CEA) promoter (Ad CEA-N116Y). We demonstrated that the expression of N116Y, growth inhibition, and apoptotic death induction were all specific to pancreatic cancer cell lines (PCI-35 and PCI-43) that were promoter positive, whereas no growth retardation was observed in human embryonic pancreas-derived cell line 1C3D3 after Ad CEA-N116Y infection. We examined the effect of Ad CEA-N116Y on the metastatic growth of PCI-43 colonies in liver, which were generated by tumor injection into the spleen of nude mice. The results showed that Ad CEA-N116Y effectively reduced the number of metastatic colonies without any complication by injecting intrasplenically five days after tumor cell inoculation. Thus N116Y can selectively suppress the metastatic growth of pancreatic tumor cell by using the CEA promoter driven adenovirus vector indicating that N116Y gene therapy may be potentially useful for the treatment of pancreatic cancer patients with liver micrometastasis

Hyaline vascular-type Castleman's disease in the hepatoduodenal ligament : Report of a case

Castleman's disease is an uncommon lymphoproliferative disorder, which occurs most commonly in the mediastinum. Sporadic reports of its occurrence in the hepatoduodenal ligament and other extrathoracic locations have also been documented. Ultimately, Castleman's disease can develop anywhere lymphoid tissue is found, and the preoperative diagnosis is often difficult. We report a case of hyaline vascular-type Castleman's disease in the hepatoduodenal ligament. An asymptomatic 26-year-old woman was admitted to our hospital for further examination of a mass found on ultrasonography. A contrast-enhanced computed tomography scan confirmed a hypervascular mass in the hepatoduodenal ligament, and angiography showed that the mass was receiving its blood supply from various arteries. These findings suggested a diagnosis of Castleman's disease and we removed the tumor without resecting any other organs. Computed tomography and angiography were helpful in establishing a correct preoperative diagnosis, which minimized the magnitude of surgery