Characterization of H2O2-induced acute apoptosis in cultured neural stem/progenitor cells.

In the present study, we characterized hydrogen peroxide (H2O2)-induced cell apoptosis and related cell signaling pathways in cultured embryonic neural stem/progenitor cells (NS/PCs). Our data indicated that H2O2 induced acute cell apoptosis in NS/PC in concentration- and time-dependent manners and selectively, it transiently increased PI3K-Akt and Mek-Erk1/2 in a dose-dependent manner. Inhibition of PI3K-Akt with wortmannin, a PI3-K inhibitor, was found to significantly increase H2O2-induced acute apoptosis and dramatically decrease basal pGSK3beta levels.

Sensitivity of the neuronal network biosensor to environmental threats.

It is widely acknowledged that there is a critical need for broad-spectrum environmental threat detection. While cells/tissue-based biosensors have been discussed for many years as a means of meeting this critical need, these kinds of systems have met with logistic concerns, in particular with regard to stability. Our group has been working with cultured neuronal networks, which have the capacity to respond to a wide range of neuroactive compounds and are sufficiently robust to be shipped to end users.

Dynamic infrared imaging of newly diagnosed malignant lymphoma compared with Gallium-67 and Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography.

Staging and therapy monitoring of malignant lymphomas relies heavily on imaging using arbitrary size criteria from computed tomography (CT) and sometimes non-specific radionuclide studies to assess the activity of the disease. Treatment decisions are based on early assessment of the response to therapy and the residual volume of the disease. Our initial experience is reported using a new noninvasive, inexpensive, and reproducible passive imaging modality, Dynamic Infrared Imaging (DIRI), which may add a new dimension to functional imaging.

A portable microelectrode array recording system incorporating cultured neuronal networks for neurotoxin detection.

Cultured neuronal networks, which have the capacity to respond to a wide range of neuroactive compounds, have been suggested to be useful for both screening known analytes and unknown compounds for acute neuropharmacologic effects. Extracellular recording from cultured neuronal networks provides a means for extracting physiologically relevant activity, i.e.

Assessing the feasibility of using neural precursor cells and peripheral blood mononuclear cells for detection of bioactive Sindbis virus.

Viruses form a significant class of bio-threat agents. Currently, the only method to determine the bioactivity of viruses in vitro is to measure viral and cellular responses after co-incubation of cells with virus. Our goal is to find biomarkers for classification of agents, establishment of bioactivity, and/or prediction of disease outcomes.

Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.

A series of 2-(thioalkyl)pentanedioic acids were synthesized and evaluated as inhibitors of glutamate carboxypeptidase II (GCP II, EC 3.4.17.

Use of temozolomide with other cytotoxic chemotherapy in the treatment of patients with recurrent brain metastases from lung cancer.

The use of chemotherapy for the treatment of brain metastases arising from lung cancer has been limited by poor efficacy and high toxicity. Temozolomide, an orally bioavailable alkylating agent that crosses the blood-brain barrier, has activity against brain metastases from both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) when used as a single agent, but response rates are low. Preclinical experiments and early clinical studies in other malignancies indicate that temozolomide may have additive or synergistic effects when used with other chemotherapeutic agents.

Incorporating electronic media into medical student education: a survey of AMSER members on computer and web use in radiology courses. Alliance of Medical Student Educators in Radiology.

Rationale And Objectives: The purpose of this study was to define the current use of information technology in radiology tutorials for medical students.

Materials And Methods: The authors conducted a Web-based survey of directors of medical school courses in radiology. The survey dealt with the details of the courses and the use of computers and the Web during the courses.

Acute neuropharmacologic action of chloroquine on cortical neurons in vitro.

Chloroquine, a common quinolone derivative used in the treatment of malaria, has been associated with neurologic side-effects including depression, psychosis and delirium. The neuropharmacologic effects of chloroquine were examined on cultured cortical neurons using microelectrode array (MEA) recording and the whole-cell patch clamp technique. Whole-cell patch clamp records under current-clamp mode also showed a chloroquine-induced depression of the firing rate of spontaneous action potentials by approximately 40%, consistent with the observations with the MEA recording, although no changes in either the baseline membrane potential or input resistance were observed.

Acute exposure of toluene transiently potentiates p42/44 mitogen-activated protein kinase (MAPK) activity in cultured rat cortical astrocytes.

It has been shown that the inhalation of toluene in rats can cause neuronal apoptosis in the central nervous system. However, the cellular and molecular effects of toluene directly on astrocytes are relatively unknown. We used primary cultures of astrocytes isolated from the neonatal rat cortex as a model to study the toluene effects on cell outcome and associated signal transduction pathways using immunostaining and Western blotting.

Toluene inhibits muscarinic receptor-mediated cytosolic Ca2+ responses in neural precursor cells.

Toluene is widely used as a component in industrial solvents and many toluene-containing products are abused via inhalation. While many studies have demonstrated its inhibitory effects on neuronal activity, the effects of toluene on receptor signaling in proliferating and differentiating neural precursor cells are presently unclear. Here, using digital video microscopy and Ca2+ imaging, we investigated the effects of acute exposure to toluene on the function of muscarinic acetylcholine receptors (mAChRs) expressed in neural precursor cells.

Laboratory bioassay studies to determine methoprene susceptibility in a natural population of Ochlerotatus taeniorhynchus from the Florida keys.

Larvae of Florida Keys Ochlerotatus taeniorhynchus collected from No Name Key were colonized and evaluated against technical S-methoprene in laboratory beaker tests. Glassware was treated with a silanizing reagent before testing to prevent methoprene attachment to the glassware. The No Name Key strain was compared with a susceptible laboratory strain of Oc.

Breast cancer screening in women previously treated for Hodgkin's disease: a prospective cohort study.

Purpose: Young women who are exposed to chest irradiation for Hodgkin's disease (HD) are at increased risk of breast cancer; this study investigated patient awareness of breast cancer risk and patient screening behavior and assessed the utility of mammographic screening in HD survivors.

Patients And Methods: This is a prospective cohort study of 90 female long-term survivors of HD who had been treated > or = 8 years previously with mantle irradiation (current age, 24 to 51 years). Participants completed surveys of their perceptions of breast cancer risk and screening behaviors and received written recommendations for breast examinations and mammography.

Design and demonstration of an automated cell-based biosensor.

Cell-based biosensors have the capacity to respond to a wide range of analytes in a physiologically relevant manner and appear well-suited for toxicity monitoring of both known and unknown analytes. One means of acquiring cellular functional information for biosensor applications involves extracellular recording from excitable cells, which can generate noninvasive and long-term measurements. Previous work from our laboratory described a prototype portable system capable of high signal-to-noise extracellular recordings, in spite of deficiencies in thermal control, fluidics handling, and absence of data acquisition (DAQ) capability.

The use of GABA(A) receptors expressed in neural precursor cells for cell-based assays.

GABA(A) receptors are known targets for certain classes of environmental neurotoxins and pharmaceutical compounds. Since few neural cell lines express functional GABA(A) receptors, the capacity to rapidly screen for compounds that affect GABA(A) receptor function is presently limited. Previous work has demonstrated that rat neural precursor cells express functional GABA(A) receptors that can be monitored via Ca(2+) imaging.

Cytotoxicity of 2-aldo- and 2-ketopyridine-N(4)-substituted thiosemicarbazones and mode of action in human Tmolt4 cells.

The 2-aldo- and 2-ketopyridine-N(4)-substituted thiosemicarbazones and their copper complexes demonstrated potent cytotoxic activity against a series of murine and human suspended cultured tumor cells. Selected compounds were active against the growth of cultured cells from solid human tumors, i.e.

Targeting of human Tmolt4 leukemic type II IMP dehydrogenase by cyclic imide related derivatives.

2,3-Dihydrophthalazine-1,4-diones, indazolones, 3-imino-1-oxoisodolines, homophthalimides, napthalidimides, diphenamides, and 6,7-dihydro-5H-dibenz[c,e]azepines proved to be potent inhibitors of the activity of human Tmolt4 T cell leukemia Type II IMP dehydrogenase (IMPDH). This inhibition was competitive, yielding Ki values in the range of 1.96 to 48.

Detection of physiologically active compounds using cell-based biosensors.

Cell-based biosensors are portable devices that contain living biological cells that monitor physiological changes induced by exposure to environmental perturbations such as toxicants, pathogens or other agents. Methods of detecting physiological changes include extracellular electrical recordings, optical measurements, and, in the future, functional genomics and proteomics. Several technical developments are occurring that will increase the feasibility of cell-based biosensors for field applications; these developments include stem cell and 3D culture technologies.

Ethanol blocks cytosolic Ca2+ responses triggered by activation of GABA(A) receptor/Cl- channels in cultured proliferating rat neuroepithelial cells.

GABA(A) receptor/Cl- channels and voltage-gated Ca2+ channels are believed to be important sites of ethanol action in the CNS. Acute exposure of ethanol potentiates GABA(A) receptor/Cl- channel activity and inhibits voltage-gated Ca2+ channels in a number of preparations, mostly post-mitotic neurons. The effects of ethanol on these channels in primary cultures of undifferentiated neural precursor cells remain unknown.

Efficacy of ground-applied ultra-low-volume malathion on honey bee survival and productivity in open and forest areas.

A study was conducted to determine the efficacy of ground ultra-low-volume malathion sprays on honey bee (Apis mellifera L.) apiaries in open and forested areas downwind from the spray route. Impact on colonies 7.

Survival and neurite outgrowth of rat cortical neurons in three-dimensional agarose and collagen gel matrices.

To better understand interactions between neurons and extracellular matrix equivalents, embryonic day-18 rat cortical neurons were immobilized and maintained in culture for up to 24 days in agarose and type I collagen gels. Using live/dead staining, neuronal cultures in low density collagen gel lasted at least 3 weeks. At 14 days, over 50% of immobilized cells in collagen gel were found viable while in low density agarose gel no cells survived.

Clinical competence assessment in radiology: introduction of an objective structured clinical examination in the medical school curriculum.

Rationale And Objectives: Traditional oral and written examinations can be limited in predicting future clinical performance. Therefore Objective Structured Clinical Examinations (OSCEs) have been introduced in other specialties. The authors assessed their value in radiology.