Relaxation of an unstable state in parametrically excited cold atoms.

We investigate the scaling behavior of the relaxation process for an unstable state near a subcritical Hopf bifurcation point. When the parametric modulation is applied to a magneto-optical trap, the atomic cloud becomes unstable and decays to the dynamic bistable states. Near the subcritical Hopf bifurcation point, we experimentally show that the relaxation process exhibits the scaling behavior; the relaxation time shows a scaling exponent of -1.

In situ induction of dendritic cell-based T cell tolerance in humanized mice and nonhuman primates.

Induction of antigen-specific T cell tolerance would aid treatment of diverse immunological disorders and help prevent allograft rejection and graft versus host disease. In this study, we establish a method of inducing antigen-specific T cell tolerance in situ in diabetic humanized mice and Rhesus monkeys receiving porcine islet xenografts. Antigen-specific T cell tolerance is induced by administration of an antibody ligating a particular epitope on ICAM-1 (intercellular adhesion molecule 1).

Phase II study of use of a single cycle of induction chemotherapy and concurrent chemoradiotherapy containing capecitabine/cisplatin followed by surgery for patients with resectable esophageal squamous cell carcinoma: long-term follow-up data.

Purpose: This phase II study evaluated the feasibility and efficacy of one cycle of induction chemotherapy, followed by concurrent chemoradiotherapy (CRT) featuring capecitabine/cisplatin, followed in turn by surgery, in the treatment of patients with resectable esophageal squamous cell carcinoma.

Methods: Between March 2003 and April 2005, 54 patients with stage II or III esophageal cancer were treated with induction chemotherapy (cisplatin 60 mg/m(2) on day 1; capecitabine 1,000 mg/m(2) bid on days 1-14) followed by concurrent radiotherapy (46 Gy in 23 fractions) and chemotherapy (cisplatin 30 mg/m(2) on days 1, 8, 15, and 22; capecitabine 800 mg/m(2) bid 5 days/week). Surgery was performed within 8 weeks of the end of radiotherapy.

Low-molecular-weight methylcellulose-based thermo-reversible gel/pluronic micelle combination system for local and sustained docetaxel delivery.

Purpose: To develop low-molecular-weight methylcellulose (LMw MC)-based gel/Pluronic F127 micelle combination system for local and sustained delivery of docetaxel (DTX).

Methods: LMw MC and Pluronic F127 were used to formulate an injectable thermo-reversible gel/micelle combination system containing DTX. The DTX-loaded combination system was characterized and its therapeutic efficacy evaluated in a subcutaneous tumor model.

Tat-enhanced delivery of metallothionein can partially prevent the development of diabetes.

Metallothioneins (MTs) are intracellular low-molecular-weight, cysteine-rich proteins with potent metal-binding and redox functions, but with limited membrane permeativity. The aim of this study was to investigate whether we could enhance delivery of MT-1 to pancreatic islets or β cells in vitro and in vivo. The second goal was to determine whether increased MT-1 could prevent cellular toxicity induced by high glucose and free fatty acids in vitro (glucolipotoxicity) and ameliorate the development of diabetes induced by streptozotocin in mice or delay the development of diabetes by improving insulin secretion and resistance in the OLETF rat model of type 2 diabetes.

Aurintricarboxylic acid promotes the conversion of naive CD4+CD25- T cells into Foxp3-expressing regulatory T cells.

Naive peripheral CD4(+)CD25(-) T cells can be converted into Foxp3-expressing regulatory T cells under appropriate stimulation conditions. Considering that continuous exposure to antigens is one of the prerequisites for the differentiation and maintenance of Treg cells, we investigated whether preventing activation-induced cell death while providing continuous TCR stimulation could promote the expression of Foxp3 in murine naive CD4(+) T cells. Among the several anti-apoptotic agents tested, aurintricarboxylic acid (ATA) was found to induce the in vitro conversion of naive CD4(+) T cells into Foxp3(+) Treg cells with suppressive activity.

Clinical feasibility and surgical benefits of video-assisted mediastinoscopic lymphadenectomy in the treatment of resectable lung cancer.

Objective: This study was performed to assess the clinical feasibility and surgical outcomes of video-assisted mediastinoscopic lymphadenectomy in the treatment of resectable lung cancer.

Methods: Between July 2004 and December 2009, we retrospectively analyzed 108 consecutive video-assisted mediastinoscopic lymphadenectomies in lung cancer patients from a prospectively collected database. Ninety-seven (89.

Nano self-assembly of recombinant human gelatin conjugated with α-tocopheryl succinate for Hsp90 inhibitor, 17-AAG, delivery.

A wide variety of drug delivery systems have been developed for the delivery of anticancer agents. One of the most frequently used natural biomaterials in drug delivery systems is polysaccharides; however, they are difficult to digest and to eliminate from the body after systemic administration due to their high molecular weight natures and the absence of degrading enzymes. Therefore, the development of degradable and eliminable natural biomaterials is critical for successful in vivo applications.

A convenient method for producing the bleomycin-induced mouse model of scleroderma by weekly injections using a methylcellulose gel.

Systemic sclerosis (SSc) is a connective tissue disease characterized by vasculopathy, excessive accumulation of extracellular matrix, and fibrosis of the skin and internal organs. An animal model of SSc, the bleomycin-induced mouse model, has been established and used extensively to investigate the pathogenesis of SSc and to seek novel therapeutic agents. We recently developed thermo-reversible combination gels that can be injected subcutaneously and are made in aqueous solution by forming a complex coacervate with the substance of interest and cationic macromolecules, followed by co-formulation with methylcellulose (MC) as a negative thermosensitive polysaccharide.

Intracellular organelle-targeted non-viral gene delivery systems.

Gene therapy is a rapidly growing approach for the treatment of various diseases. To achieve successful gene therapy, a gene delivery system is necessary to overcome several barriers in the extracellular and intracellular spaces. Polymers, peptides, liposomes and nanoparticles developed as gene carriers have achieved efficient cellular uptake of genes.

Ideal mean-field transition in a modulated cold atom system.

We show that an atomic system in a periodically modulated optical trap displays an ideal mean-field symmetry-breaking transition. The symmetry is broken with respect to time translation by the modulation period. We describe experimental observations and develop a full microscopic theory of the observed critical phenomena.

Murine mesenchymal stem cells suppress T lymphocyte activation through IL-2 receptor α (CD25) cleavage by producing matrix metalloproteinases.

Mesenchymal stem cells (MSCs) are multipotent, non-hematopoietic stem cells that exhibit the capacity to inhibit the proliferation of a variety of immune cells. However, the underlying mechanisms of the immunosuppressive effects of MSCs are still obscure. Therefore, we attempted to identify the mechanisms underlying immunosuppression toward the activated T lymphocytes by MSCs in a murine model.

Poly(oligo-D-arginine) with internal disulfide linkages as a cytoplasm-sensitive carrier for siRNA delivery.

Small interfering RNA (siRNA) has emerged as a therapeutic strategy for various diseases due to its target-specific gene silencing; however, its relatively high molecular weight, negative charge, and low stability hamper in vitro and in vivo applications. Approaches to overcome those drawbacks have relied on nonviral siRNA carriers based on cationic polymers or peptides. Nevertheless, cationic polymer-based siRNA carriers have yet to resolve intrinsic problems such as cytotoxicity and immunogenicity.

Therapeutic effects of a reducible poly (oligo-D-arginine) carrier with the heme oxygenase-1 gene in the treatment of hypoxic-ischemic brain injury.

Non-viral carriers for gene therapy have been developed to minimize carrier cytotoxicity and to enhance transfection efficiency. Previously, we synthesized a 9-arginine-based reducible high molecular weight peptide for gene delivery. For the reducible poly(oligo-D-arginines) (rPOA), 9-arginine oligopeptides are connected by internal disulfide linkages to produce a high molecular weight peptide.

Preparation and functional analysis of recombinant protein transduction domain-metallothionein fusion proteins.

In order for proteins to be used as pharmaceuticals, delivery technologies need to be developed to overcome biochemical and anatomical barriers to protein drug transport, to protect proteins from systemic degradation, and to target the drug action to specific sites. Protein transduction domains (PTDs) are used for the non-specific transduction of bio-active cargo, such as proteins, genes, and particles, through cellular membranes to overcome biological barriers. Metallothionein (MT) is a low molecular weight intra-cellular protein that consists of 61 amino acids, including 20 cysteine residues, and is over-expressed under stressful conditions.

Prolongation and enhancement of the anti-apoptotic effects of PTD-Hsp27 fusion proteins using an injectable thermo-reversible gel in a rat myocardial infarction model.

Ischemic heart disease has emerged as a leading cause of death worldwide. Conventional surgery-based therapy for this disease, especially myocardial infarction, requires additional pharmaceutical agents using heart's endogenous protective mechanism to suppress the progress and recurrence of the disease. Heat shock protein 27 (Hsp27) has been considered to be a potentially therapeutic protein for the treatment of ischemic heart disease due to its anti-apoptotic and protective effects on cardiomyocytes under stressful conditions.

Enrichment of testicular gonocytes and genetic modification using lentiviral transduction in pigs.

Gonocytes are long-lived primary germ cells that reside in the center of seminiferous cords until differentiation into spermatogonia that drive spermatogenesis. In pigs, gonocytes have research value in the production of transgenic offspring through germline modification and transplantation. However, the rarity of pig gonocytes has raised the need for an efficient isolation method.

Reducible poly(oligo-D-arginine) for enhanced gene expression in mouse lung by intratracheal injection.

Nonarginine (D-R9) has been reported to be one of the most efficacious protein transduction domains (PTDs) for the intracellular cargo delivery such as DNA, RNA, proteins, and particles. Although oligoarginines are capable of forming polyplex with DNA by electrostatic interaction, the length of oligoarginine can affect the toxicity and gene expression. The reducible poly(oligo-D-arginine) (rPOA) composed of the Cys-(D-R9)-Cys repeating unit forming disulfide bonds between terminal cysteinyl-thiol groups of short peptides was hypothesized to show efficient gene transfection without toxicity.

Ischemic heart diseases: current treatments and future.

Ischemic heart disease is a rapidly increasing common cause of death in the world. This disease is the insufficient status of oxygen within the cardiac muscles due to an imbalance between oxygen supply and demand, and a cardiac disease that occurs as a result of coronary artery stenosis. Conventional surgery-based therapy for the treatment of ischemic heart diseases has been advanced with biopharmaceutical-based therapy, such as protein, gene and cell therapy.

The heat shock protein 27 (Hsp27) operates predominantly by blocking the mitochondrial-independent/extrinsic pathway of cellular apoptosis.

Heat shock protein 27 (Hsp27) is a molecular chaperone protein which regulates cell apoptosis by interacting directly with the caspase activation components in the apoptotic pathways. With the assistance of the Tat protein transduction domain we directly delivered the Hsp27 into the myocardial cell line, H9c2 and demonstrate that this protein can reverse hypoxia-induced apoptosis of cells. In order to characterize the contribution of Hsp27 in blocking the two major apoptotic pathways operational within cells, we exposed H9c2 cells to staurosporine and cobalt chloride, agents that induce mitochondria-dependent (intrinsic) and -independent (extrinsic) pathways of apoptosis in cells respectively.

High-dose cyclophosphamide-mediated anti-tumor effects by the superior expansion of CD44(high) cells after their selective depletion.

As alkylating agents, cyclophosphamides (CTX) are used to treat various cancers and, ironically, to boost immune responses. In the present study, we attempted to elucidate the mechanism responsible for the immunomodulatory effect of high-dose CTX in an established tumor model. A single injection of high-dose CTX increased the survival rate of immunocompetent, but not immunodeficient, mice.

Controlled delivery of heat shock protein using an injectable microsphere/hydrogel combination system for the treatment of myocardial infarction.

Myocardial infarction causes a high rate of morbidity and mortality worldwide, and heat shock proteins as molecular chaperones have been attractive targets for protecting cardiomyoblasts under environmental stimuli. In this study, in order to enhance the penetration of heat shock protein 27 (HSP27) across cell membranes, we fused HSP27 with transcriptional activator (TAT) derived from human immunodeficiency virus (HIV) as a protein transduction domain (PTD). We loaded the fusion protein (TAT-HSP27) into microsphere/hydrogel combination delivery systems to control the release behavior for prolonged time periods.