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S Shimamura

Publications and source records attributed to S Shimamura.

At least 19 recordsLinked to original sources
PubMed2000

Association of Cbl with Fms and p85 in response to macrophage colony-stimulating factor.

Tyrosine phosphorylation of Cbl and its association with signal-transducing molecules in response to macrophage colony-stimulating factor (M-CSF) were analyzed by using cell lines which express the wild-type and a mutant M-CSF receptor, Fms. We found that in a clone, F723 TF-1 cells expressing mutant Fms in which tyrosine 723 had been substituted with phenylalanine, the M-CSF stimulation-dependent association between Cbl and Fms was markedly impaired. However, phosphorylation of Cbl and its association with the p85 subunit of phosphatidylinositol 3-kinase were induced in these mutant cells as seen in the wild-type fms transfectant. These results suggest that phosphorylation of tyrosine 723 is particularly important for the recruitment of Cbl to the M-CSF receptor, but is not required for the phosphorylation and binding of Cbl to signal-transducing molecules such as p85.

Amidohydrolases↗
PubMed2000

13-Week oral repeated administration toxicity study of bovine lactoferrin in rats.

Bovine lactoferrin (LF), which is an iron-binding glycoprotein in milk, was administered orally to groups of 12 males and 12 female rats at dose levels of 200, 600 and 2000mg/kg/day once daily for 13 weeks and its toxicity on repeated administration was examined. Throughout the administration period, there were no deaths caused by administration of the test compound, nor were there any adverse effects noted in the general condition of the animals. The study findings concerning body weight and food consumption, ophthalmology, urinalysis including water consumption, haematology, blood chemistry, necropsy, organ weights and histopathology revealed that there were no apparent changes due to administration of LF. Therefore, the level of LF at which no adverse effect was observed was considered to be 2000mg/kg/day for both sexes.

Administration, Oral↗
PubMed1999

NH2-terminal pentapeptide of endothelial interleukin 8 is responsible for the induction of apoptosis in leukemic cells and has an antitumor effect in vivo.

We have reported that endothelial interleukin 8 (IL-8) induces apoptosis in leukemic cells in vitro and in vivo, and that interaction between endothelial cells and leukemic cells causes induction of apoptosis through the release of endothelial IL-8 (Y. Terui et al., Biochem. Biophys. Res. Commun., 243: 407-411, 1998; Y. Terui et al., Blood, 92: 2672-2680, 1998). Here, we examined whether a pentapeptide corresponding to the NH2-terminal region of endothelial IL-8 can induce apoptosis in leukemic cells. The NH2-terminal pentapeptide Ala-Val-Leu-Pro-Arg (AVLPR) was found to significantly induce apoptosis in the leukemic cell lines K562, HL-60, Jurkat, and Daudi, as compared with the COOH-terminal pentapeptide Arg-Glu-Ala-Asn-Ser (REANS). Moreover, the NH2-terminal pentapeptide AVLPR significantly inhibited growth of i.p. and s.c. tumor masses of K562 cells and induced apoptosis in these cells in vivo. The active site of endothelial IL-8 is the NH2-terminal pentapeptide AVLPR, and this may serve as a new therapy for hematological malignancies.

Animals↗
PubMed1999

Beta(2)-microglobulin identified as an apoptosis-inducing factor and its characterization.

Major histocompatibility complex (MHC) molecules play an important role in antigen presentation for induction of tumor as well as cellular and humoral immunities. Recent studies using anti-MHC antibodies demonstrated that antibodies specific for HLA class I molecules induced cellular activation and a type of apoptosis that may be distinct from Fas-dependent or TNFR (tumor necrosis factor-alpha receptor)-dependent processes. We purified a previously untested apoptosis-inducing factor from HL-60 human leukemic cell-conditioned media to homogeneity and sequenced it. It was identified as beta(2)-microglobulin (beta(2)m), which has been previously known as thymotaxin and is a part of the HLA class I antigen complex. beta(2)m acts on both T-leukemic cells and myeloid leukemic cells to induce apoptosis, which then activates caspase 1 and 3. Cross-linking studies showed that biotinilated beta(2)m recognized an epitope distinct from those recognized by the anti-HLA class I antibody, as reported previously. We demonstrated that beta(2)m plays a previously unrecognized and important role in regulating the elimination of tumor cells, which occurs as a result of the action of beta(2)m as an apoptosis-inducing factor.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Lipid-binding and antimicrobial properties of synthetic peptides of bovine apolipoprotein A-II.

We previously showed that bovine apolipoprotein A-II (apoA-II) had antimicrobial activity against Escherichia coli and the yeast Saccharomyces cerevisiae in PBS. We have characterized here the active domain of apoA-II using synthetic peptides. A peptide corresponding to C-terminal residues Leu(49)-Thr(76) exhibited significant antimicrobial activity against E. coli in PBS, but not against S. cerevisiae. Experiments using amino-acid-substituted peptides indicated that the residues Phe(52)-Phe(53)-Lys(54)-Lys(55) are required for the activity. Peptide Leu(49)-Thr(76) induced the release of calcein trapped inside the vesicles whose lipid composition resembles that of E. coli membrane, suggesting that peptide Leu(49)-Thr(76) can destabilize the E. coli membrane. CD measurements showed that the alpha-helicity of peptide Leu(49)-Thr(76) increased from 3.5 to 36% by addition of the vesicles. When E. coli cells were incubated with peptide Leu(49)-Thr(76), some proteins were released to the external medium, probably owing to membrane destabilization caused by the peptide. In electron micrographs of E. coli cells treated with peptide Leu(49)-Thr(76), transparent nucleoids and granulated cytoplasm were observed. Amino acid substitutions, Phe(52)Phe(53)-->AlaAla (Phe(52, 53)-->Ala) in peptide Leu(49)-Thr(76) caused the loss of antimicrobial activity against E. coli, although protein-releasing activity was retained. Electron micrographs of the cells treated with peptide Leu(49)-Thr(76)(Phe(52,53)-->Ala) revealed morphological change only at the nucleoids. Therefore peptide Leu(49)-Thr(76) appears to primarily target the cytoplasm rather than the membrane of E. coli cells.

Amino Acid Sequence↗
PubMed1999

In vivo stimulatory effect of macrophage colony-stimulating factor on the number of stroma-initiating cells.

The in vivo effect of human macrophage colony-stimulating factor (M-CSF) on the number of cells that formed stromal colonies in an in vitro culture system (stroma-initiating cells; SICs) was investigated. We found that the number of SICs in the femurs of C57BL/6 mice was significantly increased by the treatment with M-CSF. We also found that the SICs were resistant to at least three different chemotherapeutic reagents, 5-fluorouracil (5-FU), cytarabine, and cyclophosphamide, because the femoral cells of mice treated with these reagents contained higher numbers of SICs than those of untreated mice. M-CSF treatment also increased the number of SICs of the reagent-pretreated mice. The SICs detected in our culture system were present only in Mac-1(-)CD45(-) cells, and the M-CSF treatment of 5-FU-pretreated mice actually increased the number of Mac-1(-)CD45(-) SICs. The Mac-1(-)CD45(-) SICs collected from mice that were pretreated with 5-FU and then treated with M-CSF formed stromal colonies under in vitro culture conditions that did not contain M-CSF but did contain a high concentration of fetal calf serum. This result suggested that SICs collected following the treatment procedure did not necessarily require the presence of M-CSF for their in vitro proliferation. Our study indicated that M-CSF has the ability to increase the number of progenitor or precursor cells for bone marrow stromal cells in vivo system.

Animals↗
PubMed1999

[A case of metachronous bilateral testicular tumors with burned-out histology in one side].

A 22-year-old man with a history of left radical orchiectomy due to a testicular tumor had bilateral pulmonary tumors. Transbronchial biopsy specimens revealed them to be germ cell tumors. The serum levels of AFP and hCG-beta were elevated. The right testis was free from a palpable mass but showed a small hyperechoic lesion on scrotal ultrasonography. We excised the echogenic focus, which was a whitish nodule under the tunica albuginea. By pathological findings it was diagnosed as a burned-out testicular tumor. This was a case with metachronous bilateral testicular tumors.

Adult↗
PubMed1999

[Lactoferrin].

Explore the source record for details and available documents.

Adult↗
PubMed1998

Association of CrkL with STAT5 in hematopoietic cells stimulated by granulocyte-macrophage colony-stimulating factor or erythropoietin.

CrkL is an adapter protein comprising Src homology (SH) 2 and SH3 domains. We investigated the molecule(s) associated with CrkL in factor-dependent cell lines. In the granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell lines TF-1 and UT-7, an approximately 95-kDa tyrosine-phosphorylated protein was precipitated along with CrkL after GM-CSF stimulation. The same protein was also observed when we used the erythropoietin (EPO)-dependent cell line UT-7/EPO, in an EPO stimulation-dependent manner. We identified it as STAT5 (signal transducer and activator of transcription 5, 96 kDa) by STAT5-specific antibodies. The direct binding of the SH2 domain of CrkL to STAT5 was demonstrated in far Western blotting and pull-down experiments using the glutathione S-transferase (GST) fusion construct CrkL-SH2. The addition of the oligopeptide containing phosphotyrosine 694 in STAT5A impaired the association between GST-CrkL-SH2 and STAT5. Furthermore, in a gel shift assay using prolactin-inducible element (PIE) as the probe, the DNA binding activity of STAT5 was inhibited by the interaction with GST-CrkL-SH2 in vitro. Finally, we found that STAT5 associated with CrkL did not bind to PIE sequence. These results suggest that CrkL participates in the Janus kinase (JAK)-STAT pathway by direct association with STAT5.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Activated endothelial cells induce apoptosis in leukemic cells by endothelial interleukin-8.

Tumor cells are eradicated by several systems, including Fas ligand-Fas and tumor necrosis factor (TNF)-tumor necrosis factor receptor (TNFR). In the previous study, we purified an apoptosis-inducing factor (AIF) to homogeneity from a medium conditioned by PDBu-treated HL-60 cells. N-terminal sequence analysis showed that AIF is identical to endothelial interleukin-8 (IL-8). A novel apoptosis system, in which endothelial cells participate via endothelial IL-8 release, is identified here. Human umbilical vein cells (VE cells) produce and secrete IL-8 by stimulation of IL-1alpha and TNF-alpha. Endothelial IL-8, which is secreted from VE cells by stimulation of IL-1alpha and TNF-alpha , induces apoptosis in myelogenous leukemia cell line K562 cells. Monocyte-derived IL-8 could not induce apoptosis in K562 cells. Moreover, interaction between VE cells and K562 cells induces the release of endothelial IL-8 from VE cells, and the attached K562 cells undergo apoptosis. Moreover, interactions between VE cell and other cell lines, such as HL-60, U937, Jurkat, and Daudi, induce the secretion of endothelial IL-8 and the induction of apoptosis in cell lines. Endothelial IL-8 significantly inhibits tumor growth of intraperitoneal and subcutaneous tumor mass of K562 cells and induces apoptosis in their cells in vivo. Endothelial IL-8 plays an important role in apoptosis involving endothelial cells, which may provide us with a new therapy for hematological malignancies.

Animals↗
PubMed1998

Identification of alternatively spliced transcripts encoding murine macrophage colony-stimulating factor.

We have isolated a novel cDNA encoding macrophage colony-stimulating factor (M-CSF) from a murine stromal cell line, ST2. The cDNA included an entire coding sequence of the M-CSF gene but contained an additional sequence of 140 base pairs (bp). Northern blot analysis demonstrated that other murine cell lines such as a fibroblastic cell line (L) and a stromal cell line (PA6) also expressed the transcripts corresponding to the clone. The nucleotide sequence analyses of the cDNA and the cloned M-CSF genome revealed that the 140-bp insertion sequence was part of intron 1 which separated exon 1 and exon 2: the former contained part of the amino acid residues of the signal sequence and the latter the rest of the signal sequence and the first 22 amino acid residues of the mature protein. The insertion of the 140-bp intron sequence not only changed the amino acid sequence of the signal peptide but also generated an in-frame termination codon. However, instead of the dysfunction of the original initiation codon, the 140-bp insertion sequence contained a putative ATG initiation codon that preserved the original open reading frame. Finally, we found that the cDNA directed the expression of a secreted and biologically active M-CSF protein when it was introduced into COS7 cells and M-CSF activity in the culture supernatants was measured using an M-CSF-dependent cell line. These results indicate the presence of an alternatively spliced M-CSF transcript which utilizes an alternate initiation codon in order to specify active M-CSF protein.

Alternative Splicing↗
PubMed1998

Identification of a novel apoptosis-inducing factor derived from leukemic cells: endothelial interleukin-8, but not monocyte-derived, induces apoptosis in leukemic cells.

The human myelogenous leukemia cell line HL-60, treated with phorbol 12, 13-dibutyrate (PDBu), produces apoptosis-inducing factors (AIFs) in leukemic cells. We have purified AIF against leukemic cell line K562 as target cells, and N-terminal amino acid sequencing analysis revealed that this purified protein is identical to endothelial cell-derived interleukin-8 ([(Ala)-IL-8]77). In Western blot analysis of supernatants of PDBu-treated HL-60 cells, only [(Ala)-IL-8]77 was detected. Moreover, recombinant human [(Ala)-IL-8]77 induced apoptosis in leukemic cell lines such as K562, HL-60, KG-1, U937, THP-1 and Jurkat, but monocyte-derived IL-8 ([(Ser)-IL-8]72) did not. Therefore [(Ala)-IL-8]77 plays an important role in inducing apoptosis against leukemic cells and may lead to a new therapy for leukemia.

Apoptosis↗
PubMed1998

Apoptosis was promoted at a nonpermissive temperature in DNA replication-defective temperature-sensitive mutants of mouse FM3A cells.

Apoptosis was promoted at the nonpermissive temperature in some temperature-sensitive (ts) mutant strains of mouse FM3A cells deficient in initiation of DNA replication. We examined expression of cell cycle regulation genes in the four ts mutant strains and found that two strains, tsFT107 and tsFT111, exhibited marked accumulation of p53 protein by a posttranscriptional mechanism at 16 h after temperature up-shift. These two strains also exhibited high levels of p21 mRNA expression, repression of cyclin A and D1 mRNAs, and obvious accumulation of underphosphorylated retinoblastoma protein. Only these two strains died by apoptosis at day 3 after up-shift, although no change was observed in the level of bax mRNA. These results suggest the existence of two types of responses after temperature up-shift in the four temperature-sensitive cell strains of the initiation of DNA replication: one type directs inappropriate DNA replication that then may produce endogenous DNA damage, p53-mediated cell cycle arrest, and subsequent apoptosis, while the other type exhibits only the p53-independent cell cycle arrest.

Animals↗
PubMed1998

Effect of macrophage colony-stimulating factor on mouse NK 1.1+ cell activity in vivo.

The effect of recombinant human macrophage colony-stimulating factor (rhM-CSF) on NK 1.1+ cell activity in vivo and in vitro was studied. An intravenous injection of rhM-CSF increased the numbers of NK 1.1+ cells in mouse spleen and blood and augmented the clearance of Yac-1 cells in vivo. Using a magnetic cell sorter (MACS), we purified NK 1.1+ cells from vehicle-injected and rhM-CSF-injected mouse spleen cells. More than 95% of the collected cells were NK 1.1 antigen-positive. NK 1.1+ cells purified from rhM-CSF-injected mouse spleen cells exhibited (a) higher cytotoxic activity against Yac-1 cells, (b) higher proliferative responsiveness to interleukin (IL)-2 and (c) a greater production of interferon (IFN)-gamma in response to IL-2 and IL-12 compared to cells purified from vehicle-injected mouse spleen cells in vitro. These results suggest that the administration of rhM-CSF increases NK 1.1+ cell numbers and activates the cells in vivo.

Animals↗
PubMed1998

Purification, primary structure, and antimicrobial activities of bovine apolipoprotein A-II.

We purified an antimicrobial protein of 76 residues, denoted bovine antimicrobial protein-1 (BAMP-1), from fetal calf serum using hydrophobic chromatography, gel filtration, and reverse-phase high-performance liquid chromatography. The amino acid sequence of BAMP-1 was similar to that of human apolipoprotein A-II (apo A-II), a major component of high-density lipoprotein (HDL), and the amino acid composition was almost identical to that of a previously reported candidate for bovine apo A-II. BAMP-1 was recovered from the post-HDL fraction, but not from the HDL fraction of the serum and was associated with a small amount of triglycerides (5%, w/w). These results suggest that BAMP-1 is the bovine homologue of apo A-II and is present in almost free form in serum. BAMP-1 showed a weak growth-inhibitory activity against Escherichia coli and yeasts tested in phosphate-buffered saline (PBS).

Amino Acid Sequence↗
PubMed1998

Effect of macrophage colony-stimulating factor (M-CSF) on mouse immune responses in vivo.

We examined the effects of recombinant human M-CSF (rhM-CSF) on mouse macrophages and immune responses in vivo. Intraperitoneal administration of rhM-CSF (20-500 microgram/ml) increased Mac-1+ cell numbers in the peritoneal cavity. The tumoricidal activities of the macrophages from vehicle-administered (V-M phi) and from rhM-CSF-administered (M-M phi) mice were the same as those observed in vitro. However, when activated by lipopolysaccharide (LPS), the tumoricidal activity of M-M phi was stronger than that of V-M phi. Intravenous administration of rhM-CSF (500 micrograms/gk) increased the number of spleen cells. Flow cytometric analysis showed that administration of rhM-CSF increased Mac-1+, B220+ and NK 1.1+ cell counts in the spleen. However, CD4+ and CD8+ cell numbers did not change. Concomitant increases were observed in levels of IL-4 and IL-10 in mouse serum following rhM-CSF administration, but no significant changes were observed in the serum level of IFN-gamma. In experiments involving mouse immune responses, the administration of rhM-CSF reduced the contact sensitivity (CS) reaction against picryl chloride (PC) and augmented IgE production in response to 2,4-dinitrophenyl (DNP), but did not affect the production of either IgM or IgC1. These results suggest that administration of rhM-CSF not only activates murine macrophages, but modulates antigen-specific immune responses in vivo.

Animals↗
PubMed1997

Biologic activity of proteoglycan macrophage colony-stimulating factor.

We compared the biologic activities of 85-kDa macrophage-CSF (85-kDa M-CSF), which is fully active, and a proteoglycan M-CSF (PG-M-CSF). Both originate from the same precursor, but the latter retains the carboxyl-terminal portion, which must be proteolytically removed from the precursor to generate 85-kDa M-CSF and which is uniquely modified by a chondroitin sulfate glycosaminoglycan chain. PG-M-CSF supported the formation of murine macrophage colonies such as 85-kDa M-CSF. Furthermore, PG-M-CSF stimulated the proliferation of murine bone marrow macrophages, an M-CSF-dependent murine cell line, and an M-CSF-responsive human cell line established by transfer of the human M-CSF receptor gene. PG-M-CSF and 85-kDa M-CSF had equivalent specific biologic activities on a molar basis in all bioassays. The activity of PG-M-CSF was not affected by enzymatically removing the glycosaminoglycan chain when assayed by the formation of macrophage colonies and proliferation of the bone marrow macrophages. We analyzed the phosphorylation on tyrosine residue(s) of the M-CSF receptor in response to these M-CSFs that trigger mitogenic responses. PG-M-CSF rapidly (within 10 min) induced receptor phosphorylation in human cells with the same potency as 85-kDa M-CSF. These results indicate that PG-M-CSF is not a latent form or precursor of 85-kDa M-CSF but a fully biologically active cytokine.

Animals↗