Clinical Safety and Tolerability of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Botulinum Neurotoxin Subtype A2, in Comparison with Subtype A1 Toxins.

All the botulinum type A neurotoxins available for clinical use are of the A1 subtype. We developed a subtype A2 low-molecular-weight (150 kD (kilo Dalton)) neurotoxin (A2NTX) with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed that its efficacy is superior to A1 toxins.

Clinical Uses of a Robot (Hybrid-Assisted Limb or HAL™) in Patients with Post-stroke Spasticity after Botulinum Toxin Injections.

Spasticity is the major cause of disabilities in stroke-survivors. Botulinum neurotoxin (BoNT) injections have been used to reduce the muscle tone in those patients, but its efficacy in functional outcome is not well delineated. We have studied the effect of a robot (Hybrid-Assisted Limb or HAL™) designed for assisting the elbow flexion and extension in those who underwent BoNT injections with reduced muscle tone.

Self-contained induction of neurons from human embryonic stem cells.

Background: Neurons and glial cells can be efficiently induced from mouse embryonic stem (ES) cells in a conditioned medium collected from rat primary-cultured astrocytes (P-ACM). However, the use of rodent primary cells for clinical applications may be hampered by limited supply and risk of contamination with xeno-proteins.

Methodology/principal Findings: We have developed an alternative method for unimpeded production of human neurons under xeno-free conditions.

Human GPM6A is associated with differentiation and neuronal migration of neurons derived from human embryonic stem cells.

Glycoprotein M6A (GPM6A) is known as a transmembrane protein and an abundant cell surface protein on neurons in the central nervous system (CNS). However, the function of GPM6A in the differentiation of neurons derived from human embryonic stem (ES) cells is unknown. To investigate the function of GPM6A in neural differentiation, we generated human ES cell lines with overexpressed (B2h-oeM6A) or suppressed (B2h-shM6A) human GPM6A.

Multitracer assessment of dopamine function after transplantation of embryonic stem cell-derived neural stem cells in a primate model of Parkinson's disease.

The ability of primate embryonic stem (ES) cells to differentiate into dopamine (DA)-synthesizing neurons has raised hopes of creating novel cell therapies for Parkinson's disease (PD). As the primary purpose of cell transplantation in PD is restoration of dopaminergic neurotransmission in the striatum, in vivo assessment of DA function after grafting is necessary to achieve better therapeutic effects. A chronic model of PD was produced in two cynomolgus monkeys (M-1 and M-2) by systemic administration of neurotoxin.

Inhibition of mouse GPM6A expression leads to decreased differentiation of neurons derived from mouse embryonic stem cells.

Glycoprotein M6A (GPM6A) is known as a transmembrane protein and an abundant cell surface protein on neurons in the central nervous system (CNS). However, the function of GPM6A is still unknown in the differentiation of neurons derived from embryonic stem (ES) cells. To investigate the function of GPM6A, we generated knockdown mouse ES cell lines (D3m-shM6A) using a short hairpin RNA (shRNA) expression vector driven by the U6 small nuclear RNA promoter, which can significantly suppress the expression of mouse GPM6A mRNA.

Monitoring of gene expression in differentiation of embryoid bodies from cynomolgus monkey embryonic stem cells in the presence of bisphenol A.

An embryonic stem (ES) cell differentiation model would facilitate analysis of developmental processes at the cellular level and the effects of embryotoxic and teratogenic factors in vitro. We explored the use of differentiation of embryoid bodies (EBs) from cynomolgus monkey ES cells for embryotoxicity testing. We determined the mRNA expression of various genes using real-time RT-PCR.

Isolation and characterization of embryonic stem-like cells from canine blastocysts.

Embryonic stem (ES) cells are pluripotent cells with the capacity to generate any type of cell. Here we describe the isolation of ES-like cells from canine blastocysts. Canine embryos were collected from beagle bitches at day 11-16 of first estrus.

Wild-type measles virus infection in human CD46/CD150-transgenic mice: CD11c-positive dendritic cells establish systemic viral infection.

We generated transgenic (TG) mice that constitutively express human CD46 (huCD46) and/or TLR-inducible CD150 (huCD150), which serve as receptors for measles virus (MV). These mice were used to study the spreading and pathogenicity of GFP-expressing or intact laboratory-adapted Edmonston and wild-type Ichinose (IC) strains of MV. Irrespective of the route of administration, neither type of MV was pathogenic to these TG mice.

Restoration of spermatogenesis and fertility in azoospermic mutant mice by suppression and reelevation of testosterone followed by intracytoplasmic sperm injection.

Advances in assisted reproduction techniques such as in vitro fertilization and intracytoplasmic sperm injection have made paternity possible for many patients with male infertility. However, at least some sperm or spermatids are required for these techniques to be successful, and patients incapable of producing spermatids cannot be helped. Male mice homozygous for the mutant juvenile spermatogonial depletion (jsd) gene show spermatogonial arrest and an elevated intratesticular testosterone level like many other experimental infertility models such as those with iradiation- or chemotherapy-induced testicular damage.