A novel nonviral gene delivery system: multifunctional envelope-type nano device.

In this review we introduce a new concept for developing a nonviral gene delivery system which we call "Programmed Packaging." Based on this concept, we succeeded in developing a multifunctional envelope-type nano device (MEND), which exerts high transfection activities equivalent to those of an adenovirus in a dividing cell. The use of MEND has been extended to in vivo applications.

Thyroid lesions in the great cormorant (Phalacrocorax carbo) of Niigata, central Japan: a possible association with dioxin accumulation.

Necropsy and histopathologic examination of three Great Cormorants (Phalacrocorax carbo) shot in Niigata, central Japan, revealed goitrous changes in the thyroids. Thyroids had a hypertrophic follicular epithelium, loss or deficiency of luminal colloid, occasional small follicles suggesting hyperplasia, and occasional collapsed follicles. Irregularly shaped follicles were frequent, and hyperemia, deposition of dark pigment, and sporadic lymphoid aggregates were also seen.

Surgical complications of salvage total laryngectomy following concurrent chemoradiotherapy.

Background: Surgical complication rates of total laryngectomy vary according to the preoperative treatments performed and patient factors. Wound complications after salvage laryngectomy following concurrent chemoradiotherapy (CCRT) were analyzed.

Methods: Eighty-six patients who had undergone total laryngectomy for laryngeal cancer at Hokkaido University Hospital, Japan, between 1990 and 2006 were divided into three groups according to preoperative treatments received: group I (n = 35) without radiotherapy (RT) or CCRT, group II (n = 17) RT alone, and group III (n = 34) low-dose CCRT.

The teleost Oryzias latipes shows telomere shortening with age despite considerable telomerase activity throughout life.

Previous studies of telomeres and telomerase have focused mostly on mammals, and data for other vertebrates are limited. We analyzed both telomere length (terminal restriction fragment length) and telomerase activity in a small freshwater teleost fish, the medaka (Oryzias latipes), and found that the telomeres shorten during ageing despite the fact that a considerable amount of telomerase activity is ubiquitously detectable throughout the life of the fish. Since the telomere attrition rate during development was greater than that in adulthood, telomere length is inversely correlated with the increase in body length.

Electric pulse stimulation induces NMDA glutamate receptor mRNA in NIH3T3 mouse fibroblasts.

Excess glutamate and Ca(2+) influx into neurons exacerbate brain damage such as ischemia. Astrocytes at the site of damage proliferate and attenuate the glutamate- and Ca(2+)-induced neuronal damage by removing excess glutamate and Ca(2+) through the N-methyl-D-aspartate (NMDA) glutamate receptor and the L-type Ca(2+) channel, respectively. Fibroblasts are commonly mobilized to the site of damage, probably supporting the restoration process.

p53 expression in concurrent chemoradiotherapy with docetaxel for head and neck squamous cell carcinoma.

Background: The current study aimed to evaluate the significance of an immunohistochemical assessment of tumor suppressor p53 as a prognostic marker in head and neck squamous cell carcinoma (HNSCC) patients treated with docetaxel and radiotherapy.

Methods: The expression of tumor suppressor p53 and its phosphorylated form at the Ser392 residue was retrospectively evaluated by immunohistochemistry in 51 Stage T1-3N0-2M0 (except T1N0 glottis) HNSCC patients who were treated with 10mg/m(2)/week docetaxel four to six times and received concurrent chemoradiotherapy.

Results: Kaplan-Meier univariate analysis revealed that no difference in rates for overall and disease-free survival (DFS) between patients with p53-positive and -negative tumors (p=0.

Screening of biochemical modulator by tumor cell permeability of doxorubicin.

We screened various food components for their ability to inhibit doxorubicin (DOX) permeability in tumor cells in vitro with the aim of finding novel modulators. Capsaicin did not change DOX permeability in the tumor cells, although the capsaicin derivatives gingerol and ferulic acid tended to promote DOX efflux. Combinations of these components with DOX were also not effective.

[Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid].

For successful cancer gene therapy via intravenous administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), which is useful for conferring stability in the systemic circulation, but is undesirable for the cellular uptake and subsequent processes. We report the development of a PEG-peptide-lipid ternary conjugate (PPD).

Preparation and characterization of polyurethane foams using a palm oil-based polyol.

Polyurethane (PU) foams were prepared using a palm oil-based polyol (PO-p). At the first stage, palm oil was converted to monoglycerides as a new type of polyol by glycerolysis. A yield of the product reached 70% at reaction temperature of 90 degrees C by using an alkali catalyst and a solvent.

Dynamic sealing of lung air leaks by the transplantation of tissue engineered cell sheets.

Current methods including the use of various biological and synthetic sealants are ineffective in the closure of intraoperative air leaks that often occur during cardiothoracic surgeries, resulting in a decreased quality of life for patients. We present the development of a novel lung air leak sealant using tissue engineered cell sheets. In contrast to previous materials such as fibrin glue, these bioengineered cell sheets immediately and permanently seal air leaks in a dynamic fashion that allows for the extensive tissue contraction and expansion involved in respiration, without any postoperative recurrences.

Tumor targeting of doxorubicin by anti-MT1-MMP antibody-modified PEG liposomes.

Immunoliposomes are potent carriers for targeting of therapeutic drugs to specific cells. Membrane type-1 matrix metalloproteinase (MT1-MMP), which plays an important role in angiogenesis, is expressed on angiogenic endothelium cells as well as tumor cells. Then, the MT1-MMP might be useful as a target molecule for tumor and neovascularity.

Two cAMP-dependent pathways differentially regulate exocytosis of large dense-core and small vesicles in mouse beta-cells.

It has been reported that cAMP regulates Ca(2+)-dependent exocytosis via protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac) in neurons and secretory cells. It has, however, never been clarified how regulation of Ca(2+)-dependent exocytosis by cAMP differs depending on the involvement of PKA and Epac, and depending on two types of secretory vesicles, large dense-core vesicles (LVs) and small vesicles (SVs). In this study, we have directly visualized Ca(2+)-dependent exocytosis of both LVs and SVs with two-photon imaging in mouse pancreatic beta-cells.

Patterned biofunctional designs of thermoresponsive surfaces for spatiotemporally controlled cell adhesion, growth, and thermally induced detachment.

In the present study, we report advanced patterned biofunctionalization of thermoresponsive surfaces for achievement of spatiotemporally controlled cell adhesion, growth, and thermally induced detachment. These patterned biofunctional thermoresponsive surfaces were prepared using dual surface modification techniques: electron beam-induced surface patterning of carboxyl-functional thermoresponsive polymers with appropriate metal masks and following site-selective biofunctionalization with biomolecules, the cell adhesive peptide (RGDS) and/or the cell growth factor (insulin; INS). Patterned co-immobilization of RGDS-INS onto thermoresponsive surfaces dominated site-selective cell adhesion and growth along with patterned biofunctional domains in the serum-free culture.

Increased Rubisco content in transgenic rice transformed with the 'sense' rbcS gene.

Rice (Oryza sativa L.) plants with substantially increased Rubisco content were obtained by Agrobacterium-mediated transformation with the rice rbcS sense gene under the control of the rice rbcS promoter. The primary transformants were screened for the ratio of Rubisco to leaf-N content, and the transformants with >120% wild-type levels of Rubisco were selected.

Clinical analysis of gastroesophageal reflux after PEG.

Background: It is difficult to predict whether or not gastroesophageal reflux (GER), such as aspiration or vomiting, will occur after PEG.

Objective: To identify factors that would support the prediction of aspiration after PEG.

Design: Case-control study.

Protein clusters associated with carcinogenesis, histological differentiation and nodal metastasis in esophageal cancer.

We examined the proteomic background of esophageal cancer. We used laser microdissection to obtain tumor tissues from 72 esophageal squamous cell carcinoma cases and adjacent normal tissues in 57 of these cases. The 2D-DIGE generated quantitative expression profiles with 1730 protein spots.

Two-photon excitation imaging of exocytosis and endocytosis and determination of their spatial organization.

Two-photon excitation imaging is the least invasive optical approach to study living tissues. We have established two-photon extracellular polar-tracer (TEP) imaging with which it is possible to visualize and quantify all exocytic events in the plane of focus within secretory tissues. This technology also enables estimate of the precise diameters of vesicles independently of the spatial resolution of the optical microscope, and determination of the fusion pore dynamics at nanometer resolution using TEP-imaging based quantification (TEPIQ).

Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid.

For successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue.

Bio-functionalized thermoresponsive interfaces facilitating cell adhesion and proliferation.

Bio-functionalized thermoresponsive culture interfaces co-immobilized with cell adhesive peptide, RGDS, and cell growth factor, insulin (INS), are investigated to promote initial cell adhesion and cell growth for further cell sheet engineering applications. These bio-functionalized interfaces were prepared by electron beam-induced copolymerization of N-isopropylacrylamide (IPAAm) with its carboxyl-derivatized analog, 2-carboxyisopropylacrylamide (CIPAAm), and grafting onto tissue culture polystyrene dishes, followed by immobilization of RGDS and/or INS to CIPAAm carboxyls. Adhesion and proliferation of bovine carotid artery endothelial cells (ECs) were examined on the RGDS-INS co-immobilized thermoresponsive interfaces.

Tissue engineered epithelial cell sheets for the creation of a bioartificial trachea.

To successfully engineer a bioartificial tracheal replacement, it is believed that the regeneration of a functional epithelial lining is a key requirement. In the present study, rabbit tracheal epithelial cells were cultured on temperature-responsive culture dishes, under normal culture conditions at 37 degrees C. By simple temperature reduction to 20 degrees C, the cultured epithelial cells were noninvasively harvested as intact sheets, without the use of any proteolytic enzymes.

Hepatocyte nuclear factor-4alpha is essential for glucose-stimulated insulin secretion by pancreatic beta-cells.

Mutations in the hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of glucose-stimulated insulin secretion by pancreatic beta-cells. HNF-4alpha, a transcription factor belonging to the nuclear receptor superfamily, is expressed in pancreatic islets as well as in the liver, kidney, and intestine. However, the role of HNF-4alpha in pancreatic beta-cell is unclear.

The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation.

Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1alpha cause a monogenic form of type 2 diabetes, maturity-onset diabetes of the young (MODY), characterized by impaired insulin secretion. Here we report that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1alpha in pancreatic beta cells.