Activation of T-cell receptor signaling in peripheral T-cell lymphoma cells plays an important role in the development of lymphoma-associated hemophagocytosis.

Peripheral T-cell lymphoma (PTCL) is a biologically diverse lymphoid malignancy. The clinical aggressiveness associated with hemophagocytic syndrome (HS) is a characteristic of PTCL, being more distinctive in CD8(+) PTCL. However, the underlying mechanism of PTCL-associated HS has not yet been fully investigated.

["Creation of mouse models for human diseases"].

To translate research findings into medicine and drug development, we have been performing in vivo research using primary human samples. Development of mouse models with reconstituted human immunity would be critical to overcome technical and ethical constraints associated with in vivo human research. To this end, we have created humanized mice by intravenously injecting purified human hematopoietic stem cells (HSCs) into immune-compromised NOD/SCID/IL2rgKO newborns.

Altered antibody production and helper T cell function in mice lacking chemokines CCL19 and CCL21-Ser.

The roles of chemokines CCL19 and CCL21 in Ab production were investigated using plt mutant mice, which lack expression of CCL19 and CCL21-ser in their lymphoid organs. In these mice, the Th response has been shown to tend towards the Th1 type because of accumulation of inflammatory dendritic cells. When plt mice were immunized with 100 μg OVA in CFA, the number of Ab-forming cells in the draining LN, and serum concentrations of OVA-specific IgM and IgG Ab, were very close to those of the control, yet IgG2a Ab in plt mice was increased.

Live-cell imaging of conidial fusion in the bean pathogen, Colletotrichum lindemuthianum.

Fusion of conidia and conidial germlings by means of conidial anastomosis tubes (CATs) is a common phenomenon in filamentous fungi, including many plant pathogens. It has a number of different roles, and has been speculated to facilitate parasexual recombination and horizontal gene transfer between species. The bean pathogen Colletotrichum lindemuthianum naturally undergoes CAT fusion on the host surface and within asexual fruiting bodies in anthracnose lesions on its host.

Alternative lengthening of telomeres pathway: recombination-mediated telomere maintenance mechanism in human cells.

Unlimitedly proliferating cells need to acquire the telomere DNA maintenance mechanism, to counteract possible shortening through multiple rounds of replication and segregation of linear chromosomes. Most human cancer cells express telomerase whereas the other cells utilize the alternative lengthening of telomeres (ALT) pathway to elongate telomere DNA. It is suggested that ALT depends on the recombination between telomere repetitive DNAs.

Bifidobacterium bifidum BF-1 suppresses Helicobacter pylori-induced genes in human epithelial cells.

Helicobacter pylori infection alters gene expression in host cells. Specifically, inflammatory chemokines such as IL-8 are upregulated in the gastric mucosa during H. pylori infection.

Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r gamma(null) humanized mice.

Whereas humanized mouse models have contributed significantly to human immunology research, human T cells developing in mouse thymic environment fail to demonstrate HLA-restricted function. To achieve HLA-restricted human immune response, we created an immune-compromised non-obese diabetic/SCID/IL2rg(null) strain (NSG) with homozygous expression of HLA class I heavy chain and light chain (NSG-HLA-A2/HHD). Transplantation of purified Lin-CD34+CD38- human hematopoietic stem cells into NSG-HLA-A2/HHD newborns resulted in the development of human CD4+ and CD8+ TCR alphabeta+ T cells and CD4-CD8- and CD8+ TCR gammadelta+ cells in recipient bone marrow and spleen.

Epitaxial lift-off for sample preparation of x-ray absorption fine structure.

We propose a simple sample preparation technique of x-ray absorption fine structure (XAFS) for its application to the individual layer of practical compound semiconductor devices. An epitaxial lift-off process enables the investigation of pure uppermost thin epitaxial layer without containing information of the bottom-side layers as well as substrate. The plain procedure offers smooth thin film with desired thickness preserving its crystallographic structure, suitable for the measurement.

Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells.

Human acute myeloid leukemia (AML) originates from rare leukemia stem cells (LSCs). Because these chemotherapy-resistant LSCs are thought to underlie disease relapse, effective therapeutic strategies specifically targeting these cells may be beneficial. Here, we report identification of a primary human LSC gene signature and functional characterization of human LSC-specific molecules in vivo in a mouse xenotransplantation model.

Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML.

Cancer stem cells have been proposed to be important for initiation, maintenance and recurrence of various malignancies, including acute myeloid leukemia (AML). We have previously reported that CD34+CD38- human primary AML stem cells residing in the endosteal region of the bone marrow are relatively chemotherapy resistant. Using a NOD/SCID/IL2rgamma(null) mouse model of human AML, we now show that the AML stem cells in the endosteal region are cell cycle quiescent and that these stem cells can be induced to enter the cell cycle by treatment with granulocyte colony-stimulating factor (G-CSF).

Fission yeast Vps1 and Atg8 contribute to oxidative stress resistance.

Organisms have evolved diverse means to protect themselves from oxidative stress. To better understand the molecular mechanisms involved in oxidative stress resistance, we screened fission yeast mutants sensitive to paraquat, a reagent acting on the mitochondria to generate reactive oxygen species. Among the mutants we isolated, we focused on a mutant defective in the vps1(+) (vacuolar protein sorting 1) gene that encodes a dynamin-related protein family member.

[Examination of the optic nerve head blood flow in patients with proliferative diabetic retinopathy treated with vitrectomy].

Purpose: To evaluate the optic nerve head blood flow level of a patient with proliferative diabetic retinopathy before and after vitrectomy, using laser speckle flow graphy (LSGF) for noninvasively ocular blood flow analysis.

Methods: Twenty three eyes of 23 patients were recruited in the present study who underwent vitrectomy at Sapporo Medical University hospital. We measured optic nerve head blood flow before and 2 weeks after operation.

Transcriptional induction of MMP-10 by TGF-beta, mediated by activation of MEF2A and downregulation of class IIa HDACs.

Transforming growth factor (TGF)-beta regulates the expression of matrix metalloproteinases (MMPs) and components of the extracellular matrix, thereby profoundly affecting the microenvironment of cells including cancerous ones. We studied MMP-10 induction by TGF-beta in mammary epithelial cells and found that the induction was dependent on the myocyte enhancer factor (MEF)-2 transcription factor. TGF-beta upregulated the gene promoter through the MEF2 site, and knockdown of the MEF2A transcription factor negatively affected MMP-10 induction, whereas its overexpression had a positive effect on the induction.

A calibration method for nanowire biosensors to suppress device-to-device variation.

Nanowire/nanotube biosensors have stimulated significant interest; however, the inevitable device-to-device variation in the biosensor performance remains a great challenge. We have developed an analytical method to calibrate nanowire biosensor responses that can suppress the device-to-device variation in sensing response significantly. The method is based on our discovery of a strong correlation between the biosensor gate dependence (dI(ds)/dV(g)) and the absolute response (absolute change in current, DeltaI).

A nanoelectronic enzyme-linked immunosorbent assay for detection of proteins in physiological solutions.

Semiconducting nanowires are promising ultrasensitive, label-free sensors for small molecules, DNA, proteins, and cellular function. Nanowire field-effect transistors (FETs) function by sensing the charge of a bound molecule. However, solutions of physiological ionic strength compromise the detection of specific binding events due to ionic (Debye) screening.

[Humanized model for acute myeloid leukemia].

To investigate human hematopoiesis and immunity in vivo, we have been making efforts to reconstitute these systems in mice by intravenously injecting purified human stem cells into NOD/SCID/IL2rgKO newborns. This xenogeneic transplantation system supports long-term engraftment, multi-lineage differentiation, and self-renewal capacity of human cord blood-derived hematopoietic stem cells (HSCs). We here introduce our recent application of the NOD/SCID/IL2rgKO newborn xenotransplant system to create in vivo models for human hematological malignancies and to understand pathophysiology of human AML.

RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway.

Budding yeast Cdc13, Stn1, and Ten1 form the CST complex to protect telomeres from lethal DNA degradation. It remains unknown whether similar complexes are conserved in higher eukaryotes or not. Here we isolated mammalian STN1 and TEN1 homologs and CTC1 (conserved telomere maintenance component 1).

Narrow band imaging applied to pleuroscopy for the assessment of vascular patterns of the pleura.

Background: Narrow band imaging (NBI), which enhances blood vessels, is a new endoscopic technology for diagnosing malignancies, but it has not been investigated for pleuroscopy.

Objectives: To evaluate the efficacy of NBI applied to pleuroscopy for detecting malignant lesions by assessing vascular patterns of the pleura.

Methods: From May 2006 to September 2008, 45 patients with undiagnosed pleural ef-fusion underwent pleuroscopy using a pleura-videoscope with white light (WL) and NBI under local anesthesia.

Ocular blood flow levels and visual prognosis in a patient with nonischemic type central retinal vein occlusion.

We look at the case of a 39-year-old female patient suffering from a sudden decrease in her left visual acuity (0.08). Her macular edema was examined using optical coherence tomography, and her optic disc blood flow was examined with laser speckle flowgraphy (LSFG).

A crucial role for adipose tissue p53 in the regulation of insulin resistance.

Various stimuli, such as telomere dysfunction and oxidative stress, can induce irreversible cell growth arrest, which is termed 'cellular senescence'. This response is controlled by tumor suppressor proteins such as p53 and pRb. There is also evidence that senescent cells promote changes related to aging or age-related diseases.

Fission yeast Ku protein is required for recovery from DNA replication stress.

The fundamental function of the conserved Ku70-Ku80 heterodimer is to promote the non-homologous end-joining (NHEJ) pathway in double-strand break repair. Although it is thought that Ku plays several roles other than NHEJ in maintaining chromosomal integrity including telomere protection, these precise functions remain unclear. In this study, we describe a novel role of fission yeast Ku proteins encoded by pku70(+) and pku80(+) genes in dealing with DNA replication stress.

Misregulation of rhodopsin phosphorylation and dephosphorylation found in P23H rat retinal degeneration.

To examine rhodopsin (Rho) functions in P23H rat, kinetics of Rho regeneration and dephosphorylation were investigated by spectrophotometric analysis and immunofluorescence labeling method using specific antibodies toward phosphorylated 334Ser or 338Ser site. Rho dephosphorylation at both sites was extremely delayed in P23H retina as compared to normal ones. Kinetics of Rho regeneration was not altered between normal and P23H rats under dark adaptation.

CCR7 ligands are required for development of experimental autoimmune encephalomyelitis through generating IL-23-dependent Th17 cells.

CCL19 and CCL21 are thought to be critical for experimental autoimmune encephalomyelitis (EAE) induction, but their precise role is unknown. We examined the role of these chemokines in inducing EAE. C57BL/6 mice lacking expression of these chemokines (plt/plt mice) or their receptor CCR7 were resistant to EAE induced with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG(35-55)) and pertussis toxin.

pH-sensitive intracellular photoluminescence of carbon nanotube-fluorescein conjugates in human ovarian cancer cells.

To add to the understanding of the properties of functionalized carbon nanotubes in biological applications, we report a monotonic pH sensitivity of the intracellular fluorescence emission of single-walled carbon nanotube-fluorescein carbazide (SWCNT-FC) conjugates in human ovarian cancer cells. Light-stimulated intracellular hydrolysis of the amide linkage and localized intracellular pH changes are proposed as mechanisms. SWCNT-FC conjugates may serve as intracellular pH sensors.