Medicine and Health Sciences Commons^™

Prophylactic Cranial Irradiation For Patients With Limited-Stage Small-Cell Lung Cancer With Response To Chemoradiation, Patricia Tai, Avi Assouline, Kurian Joseph, Larry Stitt, Edward Yu

Edward Yu

Background Previous clinical studies have generally reported that prophylactic cranial irradiation (PCI) was given to patients with a complete response (CR) to chemotherapy and chest radiotherapy in limited-stage small-cell lung cancer (SCLC). It is not clear if those with incomplete response (IR) would benefit from PCI. Patients and Methods The Saskatchewan experience from 1981 through 2007 was reviewed. Patients were treated with chest radiotherapy and chemotherapy with or without PCI (typical doses: 2500 cGy in 10 fractions over 2 weeks, 3000 cGy in 15 fractions over 3 weeks, or 3000 cGy in 10 fractions over 2 weeks). Results There were …

Novel Splenic Antigen Presenting Cell Derive From A Lin-Ckitlo Progenitor, Pravin Periasamy, Jonanthan Tan, Helen O'Neill

Helen O'Neill

The main DC subsets in murine spleen arise from BMderived precursors. Recently, a novel APC type was described in spleen. To determine if spleen contains the progenitors of this subset, a stromal coculture system was used to assess candidate progenitors for their hematopoietic potential. Here, the progenitor of that subset is identified as a spleen endogenous Lin-c-kitlo hematopoietic progenitor and is most highly enriched among the Lin-c-kitloCD34+ subset. Dendritic-like cells produced in vitro functionally resemble the previously described in vivo equivalent subset with high endocytic capacity and capability for antigen-specific activation of CD8+ T cells but not CD4+ T cells.

Investigation Into The Prevalence Of A Novel Dendritic-Like Cell Subset In Vivo, Kristin Griffiths, Jonathan Tan, Helen O'Neill

Helen O'Neill

A novel dendritic-like cell subset termed L-DC was recently identified in murine spleen based on marker expression of a homogeneous cell population derived from long-term culture of neonatal spleen. The function of L-DC is distinct from other splenic dendritic and myeloid cell subsets because of their high endocytic capacity and their ability to cross-present antigen to CD8+ T cells. This paper shows the subset to be unique to spleen and blood, with a similar, but possibly functionally distinct subset also present in bone marrow. The prevalence of the subset is low; ~6% of all dendritic and myeloid cells in the …

Investigation Into The Prevalence Of A Novel Dendritic-Like Cell Subset In Vivo, Kristin Griffiths, Jonathan Tan, Helen O'Neill

Jonathan Tan

A novel dendritic-like cell subset termed L-DC was recently identified in murine spleen based on marker expression of a homogeneous cell population derived from long-term culture of neonatal spleen. The function of L-DC is distinct from other splenic dendritic and myeloid cell subsets because of their high endocytic capacity and their ability to cross-present antigen to CD8+ T cells. This paper shows the subset to be unique to spleen and blood, with a similar, but possibly functionally distinct subset also present in bone marrow. The prevalence of the subset is low; ~6% of all dendritic and myeloid cells in the …

Preclinical Pharmacology Of Perampanel, A Selective Non-Competitive Ampa Receptor Antagonist, Michael A. Rogawski, Takahisa Hanada

Michael A. Rogawski

Perampanel [2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl) benzonitrile; E2007] is a potent, selective, orally active non-competitive AMPA receptor antagonist developed for the treatment of epilepsy. Perampanel has a 2,3′-bipyridin-6′-one core structure, distinguishing it chemically from other AMPA receptor antagonist classes. Studies in various physiological systems indicate that perampanel selectively inhibits AMPA receptor-mediated synaptic excitation without affecting NMDA receptor responses. Blocking of AMPA receptors occurs at an allosteric site that is distinct from the glutamate recognition site. Radioligand-binding studies suggest that the blocking site coincides with that of the non-competitive antagonist GYKI 52466, believed to be on linker peptide segments of AMPA receptor subunits that transduce …

Glia And Epilepsy: Excitability And Inflammation, Orrin Devinsky, Annamaria Vezzani, Souhel Najjar, Nihal C. De Lanerolle, Michael A. Rogawski

Michael A. Rogawski

Epilepsy is characterized by recurrent spontaneous seizures due to hyperexcitability and hypersynchrony of brain neurons. Current theories of pathophysiology stress neuronal dysfunction and damage, and aberrant connections as relevant factors. Most antiepileptic drugs target neuronal mechanisms. However, nearly one-third of patients have seizures that are refractory to available medications; a deeper understanding of mechanisms may be required to conceive more effective therapies. Recent studies point to a significant contribution by nonneuronal cells, the glia – especially astrocytes and microglia – in the pathophysiology of epilepsy. This review critically evaluates the role of glia-induced hyperexcitability and inflammation in epilepsy.

Effects Of Dietary Magnesium On Testicular Histology, Steroidogenesis, Spermatogenesis And Oxidative Stress Markers In Adult Rats, Amar K. Chandra, Pallav Sengupta, Haimanti Goswami, Mahitosh Sarkar

Pallav Sengupta, PhD

Ampa Receptors As A Molecular Target In Epilepsy Therapy, Michael A. Rogawski

Michael A. Rogawski

Epileptic seizures occur as a result of episodic abnormal synchronous discharges in cerebral neuronal networks. Although a variety of nonconventional mechanisms may play a role in epileptic synchronization, cascading excitation within networks of synaptically connected excitatory glutamatergic neurons is a classical mechanism. As is the case throughout the central nervous system, fast synaptic excitation within and between brain regions relevant to epilepsy is mediated predominantly by AMPA receptors. By inhibiting glutamate-mediated excitation, AMPA receptor antagonists markedly reduce or abolish epileptiform activity in in vitro preparations and confer seizure protection in a broad range of animal seizure models. NMDA receptors may …

Varying-Smoother Models For Functional Responses, Philip T. Reiss, Lei Huang, Huaihou Chen, Stan Colcombe

Philip T. Reiss

This paper studies estimation of a smooth function f(x,v) when we are given functional responses of the form f(x, ·) + error, but scientific interest centers on the collection of functions f(·,v) for different v. The motivation comes from studies of human brain development, in which x denotes age whereas v refers to brain locations. Analogously to varying-coefficient models, in which the mean response is linear in x, the “varying-smoother” models that we consider exhibit nonlinear dependence on x that varies smoothly with v. We discuss three approaches to estimating varying-smoother models: (a) methods that employ a tensor product penalty; …