Efficacy of fluoroscopy-guided endoscopic cricopharyngeal myotomy.

BACKGROUND: In endoscopic cricopharyngeal myotomy, surgeons sometimes have concerns about performing an adequate incision with only a narrow intra-cavital view from one direction. In order to overcome these issues, fluoroscopic radiography was used during endoscopic cricopharyngeal myotomy. METHODS: Peri-operative fluoroscopic radiography was utilised to check the position of the diverticuloscope, and to confirm the extent of the incision during surgery. A balloon catheter was used to determine whether the cricopharyngeal muscle was sufficiently resected. Blood loss, peri-operative complications, and functional oral swallowing scale and penetration aspiration scale scores were evaluated. RESULTS: In 12 out of 15 patients, intra-operative fluoroscopic radiography showed the diverticuloscope positioned in the post-cricoid area, and the cricopharyngeal muscle was raised and the surgery completed without adverse effect. Swallowing functions improved following surgery. CONCLUSION: Intra-operative fluoroscopy might improve endoscopic cricopharyngeal myotomy by allowing surgeons to confirm the extent of resection, and by reducing peri-operative morbidity and complication rates.

Biodegradable shape memory polymers functionalized with anti-biofouling interpenetrating polymer networks.

A novel type of shape memory polyurethane (SMPU) with high mechanical properties and biodegradability was constructed using a lactone copolymer (poly(ε-caprolactone-co-γ-butyrolactone), PCLBL), a diol- or triol-based chain extender (1,5-pentanediol, glycerol and 2-amino-2-hydroxymethyl-1,3-propanediol) and a diisocyanate cross-linker (1,6-hexamethylene diisocyanate). All types of SMPUs possessed high mechanical properties, and the shape recovery test indicated that the SMPU sheets prepared using a triol-chain extender with an amine group recovered completely the original shape at 80 °C. Moreover, the degradation products of the SMPUs were innoxious, which is an important property for use in the biomedical field. Furthermore, the SMPU sheets were interpenetrated with a zwitterionic polymer, poly(carboxymethyl betaine) (PCMB), using the interpenetrating polymer network (IPN) method to additionally introduce an anti-biofouling property. Water contact angle measurements of the surface of PCMB-introduced SMPU sheets showed a drastic reduction from 87° to approximately 30° due to the exposure of the PCMB chains from the SMPU sheets. These SMPU-IPN sheets suppressed significantly both protein adsorption and cell adhesion. Consequently, the PCLBL-PU-based SMPUs interpenetrated with PCMB are promising materials for biomedical devices because of their high mechanical, shape memory, biodegradable, and anti-biofouling properties. These materials are expected to be applied to biomaterials such as embolization materials for aneurysms and a novel type of membrane for postoperative adhesion prevention.

Advantages of anchoring growth factors to materials for neural stem/progenitor cell proliferation.

Biomaterials modified with proteins such as growth and trophic factors are known to precisely regulate various cell and tissue functions. However, the mechanisms for regulation with proteins anchored to a substrate have not been extensively studied. Although we previously evaluated specific signal transduction from epidermal growth factor (EGF) anchored to a substrate to neural stem/progenitor cells (NSPCs), the internalization of immobilized-EGF and the continuity of signaling transduction were not discussed in detail. This information is important to determine the value of growth factor-anchored biomaterials in the regulation of cells. Here, we tried to clarify the mechanisms underlying immobilized-growth factor in NSPC regulation using approaches from materials science and cell biology. In this evaluation, we used EGF chimeric protein (EGF-His) and NSPCs, and found that EGF anchored to a substrate facilitated continuous signal transduction in NSPCs attached to the substrate. In addition, the anchored-EGFs were finally internalized into cells only when the proteins formed a complex with their receptors on cell membranes detached from the substrate. Finally, we concluded that continuous signal transduction by anchoring to the substrate and final internalization into cells with the detachment of anchored-proteins from a substrate are important events for efficient regulation of cell function.

Interleukin-10 chimeric protein to protect transplanted neural progenitor cells from immune responses.

The provision of adhesive scaffolding and protection from inflammatory responses are important for enhancing graft survival. We previously developed a functional hydrogel that significantly enhances the survival of cells transplanted into the midbrain striatum. Although graft survival reached approximately 40% using this hydrogel, the survival of transplanted cells required further enhancements because it ultimately produced a decrease in the number of transplanted cells. Therefore, we developed a hydrogel system that can locally prevent the inflammatory response. This hydrogel was modified by the addition of the interleukin 10 chimeric protein (IL10CP), which is selectively released from the hydrogel when triggered by an inflammatory response. This design protects transplanted cells from inflammatory response, while other host cells remain unaffected. The IL10 domains are selectively released from the hydrogel, which act locally on the immune cells to prevent the inflammatory response without the administration of an immune suppressor. The selective release of IL10 domains from the hydrogel and their activity to prevent immune responses were evaluated using various approaches. Moreover, the ability of the IL10CP-modified hydrogel to protect cells was investigated using an in vitro co-culture with activated microglia. The IL10 incorporated into the hydrogel was selectively released by the activity of matrix-metalloproteinase 9 (MMP9), and the neural progenitor cells encapsulated in the IL10CP-immobilized hydrogel were protected from activated microglia by the release of IL10s from the hydrogel by the MMP9, produced by the activated microglia. These results show that the IL10CP-modified hydrogel will be useful as a biomaterial for improving the survival of transplanted cells.

Biodegradable microparticles for strictly regulating the release of neurotrophic factors.

A lot of research has been carried out in the last decade to find a cure for neurodegenerative diseases especially Parkinson's disease but to little avail. In this study we have demonstrated the use of poly(lactic-co-glycolic acid) (PLGA)/collagen biodegradable microparticles formed using water-in-oil-in-water (W/O/W) double emulsion method, as a neurotrophic factor delivery vehicle. The microparticles were encapsulated with glial cell-derived neurotrophic factor (GDNF) fused with collagen binding peptide (CBP) immobilized to the inner collagen phase. The novelty lies in the strict regulation of release of GDNF-CBP from the microparticles as compared to a burst release from standard microparticles. The microparticles were demonstrated to be non-cytotoxic till 300 µg/2 × 105 cells and revealed a maximum release of 250 ng GDNF-CBP/mg microparticles in 0.3% collagenase. Differentiation of neural progenitor cells (NPCs) into mature neurons was demonstrated by co-culturing microparticles with cells in a medium containing collagenase which enabled the release of encapsulated GDNF-CBP, signaling the differentiation of NPCs into microtubule-associated protein 2 (MAP2)-expressing neurons. The successful ability of these microparticles to deliver neurotrophic factors and allow differentiation of NPCs into mature neurons provides some scope in its use for the treatment of Parkinson's disease and other neurodegenerative diseases.

A sharp peak of the zero-temperature penetration depth at optimal composition in BaFe2(As(1-x)P(x))2.

In a superconductor, the ratio of the carrier density, n, to its effective mass, m*, is a fundamental property directly reflecting the length scale of the superfluid flow, the London penetration depth, λ(L). In two-dimensional systems, this ratio n/m* (~1/λ(L)(2)) determines the effective Fermi temperature, T(F). We report a sharp peak in the x-dependence of λ(L) at zero temperature in clean samples of BaFe(2)(As(1)(-x)P(x))(2) at the optimum composition x = 0.30, where the superconducting transition temperature T(c) reaches a maximum of 30 kelvin. This structure may arise from quantum fluctuations associated with a quantum critical point. The ratio of T(c)/T(F) at x = 0.30 is enhanced, implying a possible crossover toward the Bose-Einstein condensate limit driven by quantum criticality.

The theory of biological robustness and its implication in cancer.

One of the essential issues in systems biology is to identify fundamental principles that govern living organisms at the system level. In this chapter, I argue that robustness is a fundamental feature of living systems where its relationship with evolution-trade-offs among robustness, fragility, resource demands, and performance-provides a possible framework for how biological systems have evolved and been organized. In addition, diseases can be con- sidered as a manifestation of fragility of the system. In some cases, such as cancer, the disease state establishes its own robustness against therapeutic interventions. Understanding robustness and its intrinsic properties will provide us with a more profound understanding of biological systems, their anomalies, and countermeasures.

Fugu (Takifugu rubripes) sexual differentiation: CYP19 regulation and aromatase inhibitor induced testicular development.

In order to assess the involvement of aromatase CYP19 isoforms and endogenous sex steroids in gonadal sex differentiation and development of the Japanese fugu (Takifugu rubripes), an aromatase inhibitor (AI, fadrozole) was administered to developing fishes from the 'first feeding' till the 100th day after hatching. It was observed that ovarian cavity formation was inhibited by fadrozole at doses of 500 and 1000 microg/g diet, which was followed by testicular differentiation in all treated fugu. In the non-treated fugu, CYP19A was predominantly expressed in the ovary and CYP19B in the brain (in both sexes), although both were expressed interchangeably at low levels. An exceptionally high expression of CYP19B was also evident in testis throughout the study period. Both forms of CYP19 mRNA showed low levels of expression in brain and gonad with no significant differences between the two AI treatments. AI treatment inhibited CYP19A mRNA in trunk during the crucial period of ovarian cavity formation and CYP19B in gonad and brain by the end of gonadal sex differentiation. An elevation of testosterone and 11-ketotestosterone was observed which can be associated with the down-regulation of the circulating 17beta-estradiol production during the AI treatment period. After stopping AI treatment, both circulating estrogen and androgen were normalized. The current results suggest that suppression of CYP19A before and during morphological sex differentiation inhibits ovarian cavity formation in fugu. Furthermore, non-detectable limits of 17beta-estradiol and high testosterone levels by the end of the gonadal differentiation period can be ascribed to inhibition of CYP19B, suggesting that conversion of 17beta-estradiol from testosterone is plausibly regulated by CYP19B, and that this factor (CYP19B) may play an important role in AI-induced testicular development after gonadal sex differentiation through regulation of the testosterone-17beta-estradiol balance in fugu.

Comparative studies of suppression of malignant cancer cell phenotype by antisense oligo DNA and small interfering RNA.

One of the distinguishing features of malignant tumor cells is the ability to proliferate in an anchorage-independent manner; methods that effectively suppress this phenotype may be applicable to the therapeutic inhibition of the malignancy of cancers. Interfering RNA is a potentially powerful tool for cancer therapy because of its specificity of target selection and remarkably high efficiency in target mRNA suppression. We studied the use of two knockdown strategies, antisense oligo DNA (AS-ODN) and small interfering RNA (siRNA), and showed how the anchorage-independent proliferation of malignant cells could be blocked efficiently. Anchorage-independent proliferation of rat fibroblasts transformed with v-src was suppressed with only a single 1-microM dose of AS-ODN; similar suppression using siRNA required treatment with 1 nM siRNA every 12 h. With our experimental system, the molecular stability of AS-ODN allowed the use of a simple treatment regimen to control the amount of the target molecule, providing that the treatment dose was sufficiently high. In comparison, siRNA treatment was effective at lower doses, but more frequent treatment was necessary to achieve the same suppression of proliferation.

Changes in thymus- and activation-regulated chemokine (TARC) associated with allergen immunotherapy in patients with perennial allergic rhinitis.

BACKGROUND: Thymus- and activation-regulated chemokine (TARC), which is a CC chemokine receptor (CCR) 4 ligand with ability to recruit Th2 cells to inflammatory sites, is pathogenetically important in allergic rhinitis. Specific immunotherapy (IT), among the most effective therapies for allergic rhinitis, has incompletely understood mechanisms of action. TARC might be involved in some benefits of IT. METHODS: TARC in sera was assayed, obtained from 50 patients with house dust mite allergic rhinitis before and 1 year after beginning IT. Their ages ranged from 6 to 34 years (mean, 10), 30 were male and 20 were female. RESULTS: In patients whose nasal obstruction responded to IT, TARC decreased significantly with IT, while when response was defined in terms of sneezing or rhinorrhea, TARC did not change significantly. CONCLUSION: TARC might be an important target of IT in reducing obstructive allergic rhinitis.

Nanoscale friction: kinetic friction of magnetic flux quanta and charge density waves.

In analogy with the standard macroscopic friction, here we present a comparative study of the friction force felt by moving vortices in superconductors and charge density waves. Using experiments and a model for this data, our observations (1) provide a link between friction at the micro- and macroscopic scales, (2) explain the roundness of the static-kinetic friction transition in terms of thermal fluctuations, particle interactions, and system size (critical-phenomena view), and (3) explain the crossing of the kinetic friction F(k) versus velocity V for our pristine (high density of very weak defects) and our irradiated samples (with lower density of deeper pinning defects).

Use of real-time magnetic resonance image guidance in endoscopic sinus surgery.

We evaluated the effectiveness of magnetic resonance image (MRI) guidance using an optical tracking system (MRI-guided therapy: MRT) in performing endoscopic sinus surgery (ESS). The profiles of the fourteen patients in the present study were as follows: eleven with mucocele in the paranasal sinus, one with recurrent chronic sinusitis, one with maxillary cancer, and one with Graves' ophthalmopathy. Preparation of the MRT system required an additional 54 min in cases involving general anesthesia, and an additional 17 min in cases involving local anesthesia, in comparison with corresponding control groups undergoing ESS in a traditional operating room. We developed nonmetal probes that were visualized in a real-time mode and assistive devices for the optical tracking system that were equipped to avoid obstruction caused by surgical instruments as well as by the hands of surgeons. Using these unique devices, anatomic landmarks were visualized using the present MRT system. The prognosis of patients was favorable, and in particular, no patients with sinus mucocele showed a recurrence of their lesions. We concluded that the MRT system used here for performing ESS was beneficial, especially in terms of the intranasal marsupialization of sinus mucoceles and for the verification of orbital contents.

ORP150 ameliorates ischemia/reperfusion injury from middle cerebral artery occlusion in mouse brain.

The 150-kDa oxygen-regulated protein (ORP150), a novel stress protein localized to the endoplasmic reticulum (ER), is induced by hypoxia/ischemia. To determine the role of ORP150 in cerebral infarction following ischemia/reperfusion, ORP150 transgenic (TG) and knockout (KO) mice were subjected to 1 or 3 h of middle cerebral artery (MCA) occlusion followed by reperfusion for 24 h. At 24 h after 1 h of occlusion, significantly less infarct volume was evident in cerebral cortex, but not in striatum, in ORP150TG than ORP150KO mice (P<0.001). Infarct volume did not differ significantly between these groups at 24 h after 3 h of occlusion. Immunohistochemical reactivity for microtubule-associated protein (MAP)2 in the MCA territory was lost in ORP150KO mice at 24 h after 1 h of occlusion. In contrast, MAP2 staining still was present in the affected cortex of ORP150TG mice, where markedly enhanced ORP150 immunoreactivity was demonstrated. MAP2 staining had disappeared from the affected area at 24 h after 3 h of occlusion in both groups, but astrocytic ORP150 reactivity was preserved in the ORP150TG group. At 6 h after 1-h occlusion, when MAP2 staining was evident in the affected cortex, some cortical neurons of the TG mice were reactive for Bcl-xS/L. Thus, ORP150 may be cytoprotective against ischemia/reperfusion injury via reduction of ER stress and probably also inhibition of apoptosis.

Two cases of colonic tuberculosis presenting with massive melena.

The clinical symptoms of colonic tuberculosis are variable, among which massive melena is extremely rare. Herein, we report two cases of colonic tuberculosis representing with massive melena, both of whom never had active pulmonary tuberculosis. The first case was a 55-year-old woman. Although her emergency colonoscopic setting suggested colonic tuberculosis, no evidence of tuberculosis could be found at that time. We performed a therapeutic trial and observed a drastic regression of the initial changes with 4-week treatment using antituberculous agents. The second case was a 37-year-old man. His emergency colonoscopy showed lesions mimicking colon carcinoma. However, the histological examinations did not indicate malignancy. The polymerase chain reaction of colonic biopsy specimen was positive for Mycobacterium tuberculosis. Similar to the first case, a significant improvement of the initial lesions was observed after 4-week treatment using antituberculous agents. Collectively, although the massive melena is a rare manifestation, tuberculosis of the colon should be suspected in the patients with such symptom.

Evolving a lingua franca and associated software infrastructure for computational systems biology: the Systems Biology Markup Language (SBML) project.

Biologists are increasingly recognising that computational modelling is crucial for making sense of the vast quantities of complex experimental data that are now being collected. The systems biology field needs agreed-upon information standards if models are to be shared, evaluated and developed cooperatively. Over the last four years, our team has been developing the Systems Biology Markup Language (SBML) in collaboration with an international community of modellers and software developers. SBML has become a de facto standard format for representing formal, quantitative and qualitative models at the level of biochemical reactions and regulatory networks. In this article, we summarise the current and upcoming versions of SBML and our efforts at developing software infrastructure for supporting and broadening its use. We also provide a brief overview of the many SBML-compatible software tools available today.

The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models.

MOTIVATION: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. RESULTS: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. AVAILABILITY: The specification of SBML Level 1 is freely available from http://www.sbml.org/

Efficient 355-nm generation in CsB3O5 crystal.

We demonstrate UV generation in CSB3O5 (CBO) crystals grown by the top-seeded solution growth technique. 355-nm UV light was generated by use of a type II CBO crystal as a sum frequency of the fundamental light and the second harmonic of a nanosecond Nd:YVO4 laser. A 3.0-W output of the third-harmonic was obtained at a repetition rate of 31 kHz. The conversion efficiency from the fundamental light to the third harmonic reached 30%, which was 1.5 times higher than that obtained with a type II LiB3O5 crystal under the same experimental conditions.

Green revolution: a mutant gibberellin-synthesis gene in rice.

The chronic food shortage that was feared after the rapid expansion of the world population in the 1960s was averted largely by the development of a high-yielding semi-dwarf variety of rice known as IR8, the so-called rice 'green revolution'. The short stature of IR8 is due to a mutation in the plant's sd1 gene, and here we identify this gene as encoding an oxidase enzyme involved in the biosynthesis of gibberellin, a plant growth hormone. Gibberellin is also implicated in green-revolution varieties of wheat, but the reduced height of those crops is conferred by defects in the hormone's signalling pathway.

Endoscopic thyroid resection using cutaneous elevation in lieu of insufflation.

BACKGROUND: Laparoscopic surgery to resect cervical masses has gained increasing acceptance during the past decade. This report describes the authors' technique and experience using total video endoscopic surgery to resect thyroid masses. METHODS: The video camera is introduced through a 12-mm trocar inserted via a 10-mm infraclavicular incision in the sternal line. This incision will be hidden by the patient's undergarments postoperatively. An incision for a 12-mm trocar is made in each axilla, with additional incisions in the anterior chest made as necessary for the endoscope and instruments. Excellent exposure is produced by elevating the skin with hooks rather than by using carbon dioxide insufflation. This method reduces the incidence of subcutaneous emphysema and pneumomediastinum. RESULTS: Twenty-two thyroid lesions were resected using total video endoscopic surgery (adenoma, 13; cancer, 5; benign cyst, 3; and Graves' disease, 1). Procedures included thyroidectomy (12), thyroidectomy and isthmusectomy (4), and subtotal thyroidectomy (2). Subtotal cervical adenectomy was performed in 3 patients with papillary carcinoma. Cosmetic results were excellent. CONCLUSION: Endoscopic surgery of the neck is safe, minimally invasive, and produces excellent cosmetic results. However, it is in an early stage of development. Techniques have yet to be standardized, and specialized instruments are not available. The field is likely to mature as surgeons gain more experience.

The ERATO Systems Biology Workbench: enabling interaction and exchange between software tools for computational biology.

Researchers in computational biology today make use of a large number of different software packages for modeling, analysis, and data manipulation and visualization. In this paper, we describe the ERATO Systems Biology Workbench (SBW), a software framework that allows these heterogeneous application components--written in diverse programming languages and running on different platforms--to communicate and use each others' data and algorithmic capabilities. Our goal is to create a simple, open-source software infrastructure which is effective, easy to implement and easy to understand. SBW uses a broker-based architecture and enables applications (potentially running on separate, distributed computers) to communicate via a simple network protocol. The interfaces to the system are encapsulated in client-side libraries that we provide for different programming languages. We describe the SBW architecture and the current set of modules, as well as alternative implementation technologies.