Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

Background: The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV.

Use of intravenous immunoglobulin G (IVIG).

Intravenous immunoglobulin G (IVIG) has become increasingly important both as replacement therapy in primary and acquired humoral immunodeficiency and as an immunomodulatory therapy in autoimmune disease and transplantation. Multiple potential mechanisms for the effects of IVIG have now been recognized but the contribution of each mechanism in different diseases is uncertain. IVIG is generally well tolerated but serious side effects can occur and need to be addressed.

Apoptosis and complement-mediated lysis of myeloma cells by polyclonal rabbit antithymocyte globulin.

Current monoclonal antibody therapies for multiple myeloma have had limited success, perhaps due to narrow target specificity. We have previously described the ability of polyclonal rabbit antithymocyte globulin (rATG) to induce caspase- and cathepsin-mediated apoptosis in human B and plasma cells. We now extend this observation to myeloma cells.

Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans.

Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization.

An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus Challenge.

ST-246 is a low-molecular-weight compound (molecular weight = 376), that is potent (concentration that inhibited virus replication by 50% = 0.010 microM), selective (concentration of compound that inhibited cell viability by 50% = >40 microM), and active against multiple orthopoxviruses, including vaccinia, monkeypox, camelpox, cowpox, ectromelia (mousepox), and variola viruses. Cowpox virus variants selected in cell culture for resistance to ST-246 were found to have a single amino acid change in the V061 gene.

Brain-computer communication based on the dynamics of brain oscillations.

This chapter presents a review of brain-computer communication based on motor imagery and the dynamics of brain oscillations. The concept of motor imagery as experimental strategy and the two different modes of operation a brain-computer interface can have are explained. An EEG based brain switch that can control a FES-induced hand grasp of a tetraplegic and an approach towards an ECoG based brain switch are presented.

Distance learning and toxicology: new horizons for Paracelsus.

Distance learning offers many advantages to students and teachers of almost any scientific discipline. Toxicology is no exception. For example, should Paracelsus be interested in learning more about toxicology at Drexel University, he would have the opportunity to take two courses in this subject utilizing the content management software, WebCT.

Polyclonal rabbit antithymocyte globulin triggers B-cell and plasma cell apoptosis by multiple pathways.

Background: Polyclonal antithymocyte globulin (ATG) is widely used as an anti-T-cell agent for induction and treatment of acute cellular rejection in solid organ transplantation. The authors recently demonstrated that rabbit (r) ATG can be used in combination with plasmapheresis to effectively treat antibody-mediated renal allograft rejection. This observation suggested that rATG may have anti-B cell activity.

Interferon alfacon1 is an inhibitor of SARS-corona virus in cell-based models.

Preliminary data examining interferon alfacon1 treatment of SARS-CoV (severe acute respiratory syndrome-corona virus)-infected patients suggests this therapy is well tolerated and of therapeutic benefit. We report herein that interferon alfacon1, has potent in vitro antiviral activity against SARS-CoV. In a cytopathic effect protection (CPE) assay, interferon alfacon1 inhibited the generation of CPE in a dose-dependent manner with an IC50 of 0.

A pilot community intervention for young women with fetal alcohol spectrum disorders.

Fetal Alcohol Syndrome, a permanent birth defect caused by maternal alcohol use during pregnancy, is a leading preventable cause of mental retardation. Neuropsychological deficits have been well documented, however interventions developed have not been evaluated. We describe a successful 12-month community pilot intervention with 19 young women with Fetal Alcohol Spectrum Disorders (FASD).

Phase relationships between different subdural electrode recordings in man.

Almost all brain-computer interfaces (BCIs) ignore information related to the phase coupling between electroencephalogram (EEG) or electrocorticogram (ECoG) recordings from different electrodes. This paper investigates whether additional information can be found when calculating the amount of synchronization between two electrode channels by using a phase locking measurement called the phase locking value (PLV). Special emphasis is put on the beta band (around 20 Hz) as well as the gamma band (high frequencies up to 95 Hz), which can only be used when subdural electrode recordings are available.

Generation of eGFP expressing recombinant Zaire ebolavirus for analysis of early pathogenesis events and high-throughput antiviral drug screening.

Zaire ebolavirus causes large outbreaks of severe and usually fatal hemorrhagic disease in humans for which there is no effective treatment or cure. To facilitate examination of early critical events in viral pathogenesis and to identify antiviral compounds, a recombinant Zaire ebolavirus was engineered to express a foreign protein, eGFP, to provide a rapid and sensitive means to monitor virus replication in infected cells. This genetically engineered virus represents the first insertion of a foreign gene into ebolavirus.

Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge.

It is unknown whether smallpox vaccination would protect human immunodeficiency virus type 1 (HIV-1)-infected individuals, because helper CD4(+) cells, the targets of HIV-1 infection, are necessary for the induction of both adaptive CD8(+) cell and B cell responses. We have addressed this question in macaques and have demonstrated that, although smallpox vaccination is safe in immunodeficient macaques when it is preceded by immunization with highly attenuated vaccinia strains, the macaques were not protected against lethal monkeypox virus challenge if their CD4(+) cell count was <300 cells/mm(3). The lack of protection appeared to be associated with a defect in vaccinia-specific immunoglobulin (Ig) switching from IgM to IgG.

Causes and management of pleural fibrosis.

The development of pleural fibrosis follows severe pleural space inflammation which is typically associated with an exudative pleural effusion. The response of the mesothelial cell to injury and its ability, along with the basement membrane, to maintain its integrity, is vital in determining whether there is normal healing or pleural fibrosis. The formation of a fibrinous intrapleural matrix is critical to the development of pleural fibrosis.

Pleural manometry: technique and clinical implications.

Introduction: Pleural manometry during large-volume thoracentesis can prevent the development of excessively negative pleural pressures, which have been associated with re-expansion pulmonary edema; can diagnose an unexpandable lung; and can predict pleurodesis success. We currently perform pleural manometry simultaneously with both a vertical-column water manometer with an interposed resistive element, and a hemodynamic transducer connected to a standard physiologic system. We present the technique as well as the advantages and disadvantages of both systems in measuring pleural liquid pressures.

Eucalyptus as a specific irritant causing vocal cord dysfunction.

Background: Vocal cord dysfunction (VCD) is a well-recognized clinical entity that frequently mimics asthma and is characterized by inappropriate adduction of the vocal cords during inspiration. The pathogenesis of VCD has not yet been defined. The only previous report suggested that respiratory irritants may trigger paradoxical motion of the vocal cords.

The host response to smallpox: analysis of the gene expression program in peripheral blood cells in a nonhuman primate model.

Smallpox has played an unparalleled role in human history and remains a significant potential threat to public health. Despite the historical significance of this disease, we know little about the underlying pathophysiology or the virulence mechanisms of the causative agent, variola virus. To improve our understanding of variola pathogenesis and variola-host interactions, we examined the molecular and cellular features of hemorrhagic smallpox in cynomolgus macaques.

Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox.

Smallpox virus (variola) poses a significant threat as an agent of bioterrorism. To mitigate this risk, antiviral drugs and an improved vaccine are urgently needed. Satisfactory demonstration of protective efficacy against authentic variola will require development of an animal model in which variola produces a disease course with features consistent with human smallpox.

Allergen immunotherapy.

Allergen immunotherapy (also called allergy vaccine therapy) involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure. The major objectives of allergen immunotherapy are to reduce responses to allergic triggers that precipitate symptoms in the short term and to decrease inflammatory response and prevent development of persistent disease in the long term. Allergen immunotherapy is safe and has been shown to be effective in the treatment of stinging-insect hypersensitivity, allergic rhinitis or conjunctivitis, and allergic asthma.

Monkeypox virus detection in rodents using real-time 3'-minor groove binder TaqMan assays on the Roche LightCycler.

During the summer of 2003, an outbreak of human monkeypox occurred in the Midwest region of the United States. In all, 52 rodents suspected of being infected with monkeypox virus were collected from an exotic pet dealer and from private homes. The rodents were euthanized and submitted for testing to the United States Army Medical Research Institute of Infectious Diseases by the Galesburg Animal Disease Laboratory, Illinois Department of Agriculture.

Toward a direct brain interface based on human subdural recordings and wavelet-packet analysis.

Highly accurate asynchronous detection of movement related patterns in individual electrocorticogram channels has been shown using detection based on either event-related potentials (ERPs) or event-related desynchronization and synchronization (ERD/ERS). A method using wavelet-packet features selected with a genetic algorithm was proposed to simultaneously detect ERP and ERD/ERS and was tested on data from seven subjects and four motor tasks. The proposed wavelet method performed better than previous methods with perfect detection for four subject/task combinations and hit percentages greater than 90% with false positive percentages less than 15% for at least one task for all seven subjects.

Adolescents define sexual orientation and suggest ways to measure it.

Researchers disagree on how to assess adolescent sexual orientation. The relative importance of various dimensions (e.g.

Drug-induced pleural disease.

Drug-induced pleural disease is uncommon and less known to clinicians than drug-induced parenchymal lung disease. Pleural reactions from drugs manifest as pleural effusions, pleural thickening, or pleuritic chest pain, and may occur in the absence of parenchymal infiltrates. The clinician should be cognizant of the possibility of a drug-induced pleural reaction.