Rapid Expansion of Highly Functional Antigen-Specific T Cells from Patients with Melanoma by Nanoscale Artificial Antigen-Presenting Cells.

Purpose: Generation of antigen-specific T cells from patients with cancer employs large numbers of peripheral blood cells and/or tumor-infiltrating cells to generate antigen-presenting and effector cells commonly requiring multiple rounds of restimulation . We used a novel paramagnetic, nanoparticle-based artificial antigen-presenting cell (nano-aAPC) that combines anti-CD28 costimulatory and human MHC class I molecules that are loaded with antigenic peptides to rapidly expand tumor antigen-specific T cells from patients with melanoma.

Experimental Design: Nano-aAPC-expressing HLA-A*0201 molecules and costimulatory anti-CD28 antibody and HLA-A*0201 molecules loaded with MART-1 or gp100 class I-restricted peptides were used to stimulate CD8 T cells purified from the peripheral blood of treatment-naïve or PD-1 antibody-treated patients with stage IV melanoma.

Detection and recognition thresholds for five basic tastes in patients with mild cognitive impairment and Alzheimer's disease dementia.

Background: Patients with Alzheimer's disease dementia (ADD) are thought to exhibit taste disorders; however, this has not been extensively studied. We investigated gustatory functions and factors affecting taste in patients with ADD or mild cognitive impairment (MCI) and in non-demented controls (NDCs) and evaluated associations between cognitive impairment and gustatory functions.

Methods: We recruited 29 patients with ADD, 43 with MCI, and 14 with NDCs.

Novel anti-EPHA2 antibody, DS-8895a for cancer treatment.

Overexpression of EPHA2 has been observed in multiple cancers and reported to be associated with poor prognosis. Here, we produced an afucosylated humanized anti-EPHA2 monoclonal antibody (mAb), DS-8895a for cancer treatment. The antibody recognizes the extracellular juxtamembrane region of EPHA2 and therefore can bind to both full-length and truncated forms of EPHA2, which are anchored to cell membranes and recently reported to be produced by post-translational cleavage in tumors.

GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy.

Temporal lobe epilepsy (TLE) is accompanied by an abnormal location of granule cells in the dentate gyrus. Using a rat model of complex febrile seizures, which are thought to be a precipitating insult of TLE later in life, we report that aberrant migration of neonatal-generated granule cells results in granule cell ectopia that persists into adulthood. Febrile seizures induced an upregulation of GABA(A) receptors (GABA(A)-Rs) in neonatally generated granule cells, and hyperactivation of excitatory GABA(A)-Rs caused a reversal in the direction of granule cell migration.

The ratio of 'deleted in colorectal cancer' to 'uncoordinated-5A' netrin-1 receptors on the growth cone regulates mossy fibre directionality.

Proper axonal targeting is fundamental to the establishment of functional neural circuits. The hippocampal mossy fibres normally project towards the CA3 region. In the hippocampi of patients with temporal lobe epilepsy and related animal models, however, mossy fibres project towards the molecular layer and produce the hyperexcitable recurrent networks.

Cryopreservation of granule cells from the postnatal rat hippocampus.

Although primary cultures of neurons are essential methods for cell biological and pharmacological researches, many animals must be sacrificed for each experiment. Here we introduce a novel system to cryopreserve hippocampal granule cells (GCs) prepared from postnatal rats. Being thawed after as long as 60 days of cryopreservation, GCs expressed the mature neuronal marker MAP-2 and elongated single tau-1-positive axons and multiple tau-1-negative dendrites.

A low-cost method for brain slice cultures.

Low-cost, simple procedures for organotypic tissue cultures are desirable for high-throughput biological experiments such as large-scale medical/drug screening. We present a practical and economical method to cultivate brain slices using hydrophilic filtration membranes. With a cost reduction of more than 90%, this technique allows us to prepare hippocampal slice cultures that are morphologically and functionally indistinguishable from those obtained by the widely used Millicell-CM method.