Immunocytochemical analysis of cubilin-mediated endocytosis of high density lipoproteins (HDL) in epithelial cells of the rat visceral yolk sac.

Cubilin was recently shown to function as an endocytic receptor for high density lipoprotein (HDL) holoparticles and apolipoprotein A-I (apo A-I), the main protein constituent of HDL. In the present study, we analyzed the distribution and intracellular trafficking of cubilin and HDL in rat visceral yolk sac epithelial cells. After epithelial cells were loaded with apolipoprotein E-free HDL for 30 min in vitro, double immunofluorescence showed that the apical cytoplasm of the cells was strongly stained with anti-cubilin antibodies and anti-apo A-I/HDL.

Transforming growth factor beta receptor I kinase inhibitor down-regulates cytokine secretion and multiple myeloma cell growth in the bone marrow microenvironment.

Purpose: Transforming growth factors (TGFs) have pleiotropic biological effects on tumor cells and their environment. In multiple myeloma (MM), we have reported that bone marrow stromal cells (BMSCs) from MM patients produce more TGF-beta1 than BMSCs from healthy donors, which in turn induces interleukin (IL)-6 secretion. We show here that the TGF-beta receptor I kinase inhibitor SD-208 significantly decreases secretion of both IL-6 and vascular endothelial growth factor (VEGF) from BMSCs, as well as tumor cell growth triggered by MM cell adhesion to BMSCs.

Starvation triggers the delivery of the endoplasmic reticulum to the vacuole via autophagy in yeast.

Autophagy is a survival mechanism necessary for eukaryotic cells to overcome nutritionally challenged environments. When autophagy is triggered, cells degrade nonselectively engulfed cytosolic proteins and free ribosomes that are evenly distributed throughout the cytoplasm. The resulting pool of free amino acids is used to sustain processes crucial for survival.

p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells.

Although PS-341 (bortezomib) is a promising agent to improve multiple myeloma (MM) patient outcome, 65% of patients with relapsed and refractory disease do not respond. We have previously shown that heat shock protein (Hsp)27 is upregulated after PS-341 treatment, that overexpression of Hsp27 confers PS-341 resistance, and that inhibition of Hsp27 overcomes PS-341 resistance. Since Hsp27 is a downstream target of p38 mitogen-activated protein kinase (MAPK)/MAPK-mitogen-activated protein kinase-2 (MAPKAPK2), we hypothesized that inhibition of p38 MAPK activity could augment PS-341 cytotoxicity by downregulating Hsp27.

[Evaluation of bacterial flora in contaminated soil as a countermeasure against H2S gas production].

Gas productions in illegal dumping sites and waste landfills have caused serious problems. The gas production was induced by bacterial flora inhabited soils. In order to construct a culture independent evaluation system of the soil bacteria, bacterial communities were analyzed quantitatively and qualitatively, about 16 soil samples at 4 sites, both using culture and culture-independent methods.

Mechanisms by which SGN-40, a humanized anti-CD40 antibody, induces cytotoxicity in human multiple myeloma cells: clinical implications.

CD40 is expressed on B-cell malignancies, including human multiple myeloma (MM) and a variety of carcinomas. We examined the potential therapeutic utility of SGN-40, the humanized anti-CD40 monoclonal antibody, for treating human MM using MM cell lines and patient MM cells (CD138(++), CD40(+)). SGN-40 (0.

Apoptosis- and cell cycle-associated gene expression profiling of histiocytic necrotising lymphadenitis.

Cell death is of two types; necrosis and apoptosis. In histiocytic necrotising lymphadenitis (HNL), apoptosis is the main form of cell death. Apoptosis results in the formation of nuclear debris, which is one of the characteristic features of HNL.

Association of early endosomal autoantigen 1 with macropinocytosis in EGF-stimulated A431 cells.

Association of early endosomal autoantigen 1 (EEA1) with macropinosomes was examined in EGF-stimulated A431 cells by dual labeling with immunofluorescence of anti-EEA1 and FITC-dextran (FDx), a fluid-phase endocytic marker. Addition of EGF to A431 cells drastically enhanced macropinosome formation. Newly formed macropinosomes labeled with 5-min pulse of FDx were located at the cell periphery and labeled weakly for EEA1.

Expression and alternative splicing pattern of human telomerase reverse transcriptase in human lung cancer cells.

Telomerase activity is generally considered to be necessary for cancer cells to avoid senescence. The expression of human telomerase reverse transcriptase (hTERT) is believed to be a rate-limiting step in telomerase activation. Recently, it has been proposed that the alternative splicing of hTERT is also involved in regulation of telomerase activity.

Differential expression of chemokines, chemokine receptors, cytokines and cytokine receptors in diffuse large B cell malignant lymphoma.

Host immunity, particularly T cell immunity (Th1/Th2 balance), plays an important role in clinicopathological features of malignant disease. However, the T cell immunity has not been fully investigated in patients with lymphoid malignancies. Recent studies suggested the important role of dysregulation of the endogenous immune system in lymphomagenesis.

Effects of oligonucleotide N3'-->P5' thio-phosphoramidate (GRN163) targeting telomerase RNA in human multiple myeloma cells.

Telomeres are specialized nucleoprotein complexes that protect against fusion and degradation of linear chromosomes. Critical shortening of telomeres leads to irreversible cessation of cell division, whereas telomerase elongates telomere sequences to compensate for losses that occur with each round of DNA replication. Continued proliferation of tumor cells requires this enzyme to maintain chromosomal stability and to counteract the cellular mitotic clock.

Induction of tube formation by angiopoietin-1 in endothelial cell/fibroblast co-culture is dependent on endogenous VEGF.

The angiopoietin-1 (Ang1)/Tie2 receptor system is known to be important for angiogenesis and vascular remodeling. However, its contribution to the survival and morphogenesis of endothelial cells is still not well elucidated. In this study, we analyzed the role of the Ang1/Tie2 pathway in cell survival and tube formation using a human umbilical vein endothelial (HUVE) cell and fibroblast co-culture system.

Differential chemokine, chemokine receptor, cytokine and cytokine receptor expression in pulmonary adenocarcinoma: diffuse down-regulation is associated with immune evasion and brain metastasis.

Pulmonary adenocarcinoma is frequently associated with brain metastasis at some stage during the disease course. Host immunity, particularly T cell immunity, plays an important role in the clinicopathological features of carcinoma proliferation and metastasis. Cytokines and chemokines are members of a family of small secreted proteins.

Th1, Th2, and activated T-cell marker and clinical prognosis in peripheral T-cell lymphoma, unspecified: comparison with AILD, ALCL, lymphoblastic lymphoma, and ATLL.

A new World Health Organization classification was recently proposed. However, classification of peripheral T-cell lymphomas remains to be clarified. Particularly, unspecified type was considered as a heterogeneous category.

Differential chemokine, chemokine receptor and cytokine expression in Epstein-Barr virus-associated lymphoproliferative diseases.

T cell immunity plays an important role in the clinicopathology of Epstein-Barr virus (EBV)-associated diseases. Acute EBV-induced infectious mononucleosis (IM) is a common self-limiting disease, however, other EBV-associated diseases, including chronic active EBV infection (CAEBV), NK cell lymphoma (NKL), and Hodgkin's lymphoma (HL), exhibit distinct clinical features. Chemokines are members of a family of small-secreted proteins.

Imbalance between apoptosis and telomerase activity in myelodysplastic syndromes: possible role in ineffective hemopoiesis.

The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hyper-cellular bone marrow. This is thought to be due to apoptosis of hematopoietic bone marrow cells, resulting in ineffective hematopoiesis. The heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is involved in pre-mRNA processing and binds to telomeric cDNA repeats.

Imbalances of chemokines, chemokine receptors and cytokines in Hodgkin lymphoma: classical Hodgkin lymphoma vs. Hodgkin-like ATLL.

Classical Hodgkin lymphoma (HL) is characterized by the presence of Hodgkin and Reed-Sternberg cells (H&RS) and a prominent lymphocytic infiltration. We previously reported Hodgkin-like adult T-cell leukemia/lymphoma (HL-like ATLL) (new WHO classification). Various CXC and CC chemokines are expressed on H&RS cells and the relationships between chemokines and the chemokine receptor (R) are thought to be important for selectivity of local immunity of Th1 and Th2 T cells.

Expression of chemokine receptor CXCR3 and its ligand, mig, in gastric and thyroid marginal zone lymphomas. Possible migration and autocrine mechanism.

Chemokine receptors mediate the migration of lymphocytes through the binding of ligands, and the expression is differentially regulated in lymphocyte subsets. CXCR3 is usually expressed in Th1 T cells, however, recently is reported to be expressed in B cell chronic lymphocytic leukemia, mucosa-associated lymphoid tissue type lymphoma (MALT) (extranodal marginal zone lymphoma), and other B cell non-Hodgkin lymphomas. Our study was designed to investigate the expression of CXCR3 and its ligand Mig, and their relationships in MALT using immunohistochemistry.

The early secretory pathway contributes to autophagy in yeast.

Autophagy is a starvation response in eukaryotes by which the cell delivers cytoplasmic components to the vacuole for degradation, and is mediated by a double membrane structure called the autophagosome. We have previously proposed that the specific combination of COPII like components, including Sec24p, is required for autophagy (Ishihara, N. et al.

Reduced expression of heterogeneous nuclear ribonucleoprotein B1 in adult T-cell lymphoma/leukemia.

It is considered that hnRNP B1 expresses similarly in the various types of tumor cells. Recently, we demonstrated high B1 expression in B-cell lymphoma and carcinoma. To evaluate the difference of B1 expression between B and T-cell lymphoma, we immunologically studied the B1 expression in 22 cases with nodal T-cell lymphoma, comprising adult T-cell leukemia/lymphoma (ATLL; n=15) and angioimmunoblastic T-cell lymphoma (AILD; n=7), using an anti-hnRNP B1 monoclonal antibody, 2B2.

Overexpression of heterogeneous nuclear ribonucleoprotein B1 in lymphoproliferative disorders: high expression in cells of follicular center origin.

It is reported that overexpression of hnRNP A2 and B1 proteins is useful for detecting early cancers, and that B1, a splicing minor isoform of A2, is more specific than A2. The B1 expression is still undetermined in human lymphoid tissues. We quantitatively studied the B1 expression in 85 lymph node specimens, comprising reactive lymphoid hyperplasia (RLH; n=8), B-cell lymphoma (n=23), T-cell lymphoma (n=22), and metastatic carcinoma (n=32).

Peroxisomal targeting signal receptor Pex5p interacts with cargoes and import machinery components in a spatiotemporally differentiated manner: conserved Pex5p WXXXF/Y motifs are critical for matrix protein import.

Two isoforms of the peroxisomal targeting signal type 1 (PTS1) receptor, termed Pex5pS and (37-amino-acid-longer) Pex5pL, are expressed in mammals. Pex5pL transports PTS1 proteins and Pex7p-PTS2 cargo complexes to the initial Pex5p-docking site, Pex14p, on peroxisome membranes, while Pex5pS translocates only PTS1 cargoes. Here we report functional Pex5p domains responsible for interaction with peroxins Pex7p, Pex13p, and Pex14p.

Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion.

Double membrane structure, autophagosome, is formed de novo in the process of autophagy in the yeast Saccharomyces cerevisiae, and many Apg proteins participate in this process. To further understand autophagy, we analyzed the involvement of factors engaged in the secretory pathway. First, we showed that Sec18p (N-ethylmaleimide-sensitive fusion protein, NSF) and Vti1p (soluble N-ethylmaleimide-sensitive fusion protein attachment protein, SNARE), and soluble N-ethylmaleimide-sensitive fusion protein receptor are required for fusion of the autophagosome to the vacuole but are not involved in autophagosome formation.

Electrophysiological studies and physical examinations in entrapment neuropathy: sensory and motor functions compensation for the central nervous system in cases with peripheral nerve damage.

We performed electrophysiological studies and objective physical examinations in 60 patients with carpal tunnel syndrome and 21 patients with cubital tunnel syndrome. Compared with our normal data, the sensory nerve conduction velocity across the wrist was defined as abnormal in 97% of the carpal tunnel syndrome patients, the corresponding value of the amplitude of the sensory nerve action potential was 58% and the value of the two point discrimination test was 28% while the value of the Semmes-Weinstein monofilament test was defined as abnormal in 64% of the cases. In cubital tunnel syndrome patients, motor nerve conduction velocity across the elbow was defined as abnormal in 91%, the amplitude of the M-wave was 96%, manual muscle testing was 63% and their side pinch strength was defined as abnormal in 24% of the cases.

Expression of hnRNP B1 in four major histological types of lung cancers.

Heterogeneous nuclear ribonucleoprotein B1 is one of the nuclear pre-mRNA binding proteins involved in RNA metabolism. Recently, over-expression of B1 has been reported to be useful in the early detection of squamous cell carcinomas of the lung. To elucidate its significance in other histological types of lung cancers, we carried out a comparative study, four major types of lung cancers and normal lung tissues.