Search PubMed⌕ Search

Biomedical subjects

M Tomida

Publications and source records attributed to M Tomida.

At least 37 records · Page 2Linked to original sources
PubMed1993

Pregnancy associated increase in mRNA for soluble D-factor/LIF receptor in mouse liver.

We examined the distribution of mRNAs for differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) receptor in various mouse tissues by Northern blotting. A mouse cDNA fragment encoding the D-factor receptor was prepared by the RT-PCR method using human cDNA sequences as primers. The smallest mRNA (3 kb) was present in the liver, but not detectable in other tissues examined. Larger mRNAs (5 and 10 kb) were present in the placenta and the M1 cells, and also detectable in the liver, kidney, heart, lung, brain and embryos. Expression of 3 kb mRNA in the liver increased during pregnancy, being 20 times the initial level on day 15. D-factor receptor cDNAs were isolated from a cDNA library prepared from the liver of a pregnant mouse. Most of the cDNA clones encoded a soluble receptor. A cDNA probe specific for the cellular receptor did not hybridize with 3 kb mRNA in the liver. These results suggest that 3 kb mRNA encodes a soluble D-factor receptor and that the liver is the primary site of synthesis of this soluble receptor.

Amino Acid Sequence↗
PubMed1993

Pregnancy associated increase in differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF)-binding substance(s) in mouse serum.

Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) is known to have multiple biological activities besides induction of differentiation of mouse myeloid leukemia M1 cells. Little is known about how its activities are regulated in vivo, but it has been suggested to play a regulatory role in the mechanisms involved in development of mice. In this study, we found that a single class of D-factor-binding substance is present in normal mouse serum and that it increases transiently in the late stage of pregnancy. It inhibits the induction of differentiation of mouse myeloid leukemic M1 cells by D-factor by blocking the binding of this factor to the cells. It is a heat-labile protein with an apparent molecular weight of 130,000-150,000. The binding of 125I-D-factor to the substance is specific since it was inhibited by excess unlabeled D-factor, but not by interleukin 6 or interferon gamma. The dissociation constant of the binding substance for mouse D-factor in normal mouse serum is 6.6-9.4 nM. In the late stage of pregnancy, the amount of the D-factor-binding substance in the serum apparently increases about 30-fold. These results suggest that the D-factor-binding substance regulates the activity of D-factor during embryonic development of mice.

Animals↗
PubMed1992

Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor): regulation of its production and possible roles in bone metabolism.

Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor), expression of its mRNA, and possible roles in bone metabolism were studied in murine primary and clonal osteoblast-like cells. Local bone-resorbing factors such as IL-1, TNF alpha, and LPS strongly induced expression of LIF/D-factor mRNA in both clonal MC3T3-E1 cells and primary osteoblast-like cells. Neither parathyroid hormone nor 1 alpha,25-dihydroxyvitamin D3 stimulated expression of LIF/D-factor mRNA. LIF/D-factor per se did not stimulate expression of its own mRNA. Appreciable amounts of LIF/D-factor were detected in synovial fluids from rheumatoid arthritis (RA) patients but not in those with osteoarthritis (OA). Simultaneous treatment with LIF/D-factor, IL-1, and IL-6 at the concentrations found in synovial fluids from RA patients greatly enhanced bone resorption, though these cytokines did not stimulate bone resorption when separately applied. This suggests that LIF/D-factor produced by osteoblasts is in concert with other bone-resorbing cytokines such as IL-1 and IL-6 involved in the bone resorption seen in the joints of RA patients. LIF/D-factor specifically bound to MC3T3-E1 cells with an apparent dissociation constant of 161 pM and 1,100 binding sites/cell. LIF/D-factor dose-dependently suppressed incorporation of [3H]thymidine into MC3T3-E1 cells. In addition, it potentiated the alkaline phosphatase activity induced by retinoic acid, though LIF/D-factor alone had no effect on enzyme activity. These results suggest that LIF/D-factor is involved in not only osteoclastic bone resorption but also osteoblast differentiation in conjugation with other osteotropic factors.

Acid Phosphatase↗
PubMed1992

Prolongation by differentiation-stimulating factor/leukemia inhibitory factor of the survival time of mice implanted with mouse myeloid leukemia cells.

Mouse myeloid leukemic M1 cells can be induced to differentiate into macrophages by differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF). We examined the effect of D-factor on the survival times of syngeneic mice implanted with two different clones (T-22 and R-4) of M1 cells. D-factor induced differentiation and suppressed DNA synthesis of sensitive T-22 cells but not resistant R-4 cells in vitro. For in vivo experiments, we used recombinant mouse D-factor (rmD-factor) produced in mammalian cells, which is glycosylated and is more stable in vitro and in vivo than unglycosylated rmD-factor produced in Escherichia coli. Treatment with rmD-factor prolonged the survival times of mice implanted with T-22 cells but not R-4 cells.

Animals↗
PubMed1992

Effect of recombinant human D-factor on the growth of leukemic blast progenitors from acute myeloblastic leukemia patients.

We studied the effects of D-factor on the growth of leukemic blast progenitors from 15 patients with acute myeloblastic leukemia and two leukemia cell lines in methylcellulose and suspension cultures. When stimulated by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor or interleukin-3, leukemic blast progenitors undergo terminal division with limited differentiation in methylcellulose culture, forming blast colonies. Leukemic blast progenitors can renew themselves. The self-renewal can be detected as secondary colony formation after replating primary blast colonies in fresh methylcellulose media and by the growth of clonogenic cells in suspension culture. D-Factor suppressed primary and secondary colony formation in methylcellulose culture. Furthermore, D-factor suppressed clonogenic cell recovery in suspension culture. The suppression by D-factor of the growth of leukemic blast progenitors was not significantly dependent upon the colony-stimulating factors used as growth-stimulating factors. High concentration of G-CSF did not overcome the suppressive effect of D-factor. The results indicate that D-factor is effective in suppressing not only terminal division but also self-renewal of leukemic blast progenitors.

Adult↗
PubMed1992

[Function, molecular structure and gene expression regulation of receptor for D-factor/LIF].

Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) is a cytokine inducing differentiation of mouse myeloid leukemic M1 cells. IL-6, oncostatin M (OSM) and G-CSF also induce differentiation of M1 cells. These four cytokines are suggested to be members of a single cytokine family. The LIF receptor is structurally related to the gp130 signal-transducing component of the IL-6 receptor and to the G-CSF receptor. The high-affinity receptors for LIF, OSM and IL-6 share the common subunit, gp130. This provides an explanation for the functional redundancy of those cytokines.

Animals↗
PubMed1991

Both D factor/LIF and IL-6 inhibit the differentiation of mouse teratocarcinoma F9 cells.

Differentiation-stimulating factor (D factor)/leukemia inhibitory factor (LIF) and IL-6 are reported to be cytokines having multifaced functions including the induction of differentiation in mouse myeloid leukemia M1 cells. We here report that both D factor/LIF and IL-6 inhibit the differentiation of mouse teratocarcinoma F9 cells induced by retinoic acid alone or combined with dibutyryl cAMP. From the microscopic observation as well as Northern blot analysis using cDNA probes encoding several marker proteins for differentiation of F9 cells, we concluded that D factor/LIF and IL-6 are functionally closely related in the induction of differentiation in M1 cells and in the inhibition of F9 differentiation.

Alkaline Phosphatase↗
PubMed1990

Inhibition of development of Na(+)-dependent hexose transport in renal epithelial LLC-PK1 cells by differentiation-stimulating factor for myeloid leukemic cells/leukemia inhibitory factor.

Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor is a cytokine inducing differentiation of mouse myeloid leukemic M1-T22 cells. The effect of recombinant human D-factor on growth and differentiation of pig kidney LLC-PK1 cells was examined. LLC-PK1 cells did not concentrate alpha-methylglucoside during their early growth in culture but developed the capacity to concentrate this hexose as they reached confluence and their growth rate decreased. Purified D-factor caused dose-dependent inhibition of the development of this concentrative capacity. It did not affect the growth rate of the cells, but inhibited the formation of multicellular domes in confluent cultures. LLC-PK1 cells were found to have high-affinity binding sites (831 per cell) for D-factor with a dissociation constant of 197 pM.

Alkaline Phosphatase↗
PubMed1990

Protein factors that regulate the growth and differentiation of mouse myeloid leukaemia cells.

We have purified and characterized several protein factors that regulate the growth and differentiation of mouse myeloid leukaemia M1 cells. The differentiation factor (D-factor) from conditioned medium (CM) of Ehrlich ascites tumour cells is a glycoprotein of Mr 40,000-50,000. Its amino acid sequence was found to be almost identical to that of leukaemia inhibitory factor (LIF) from Krebs II ascites cells. The differentiation inhibitory factor (I-factor) from the CM of variant M1 cell clones which were resistant to several differentiation inducers is a basic protein of apparent Mr 68,000. The growth inhibitory factor (GI-factor) that specifically inhibits the partially differentiated and still growing monocytic leukaemia M1 cells was isolated from the CM of a clone of M1 cells resistant to the differentiation inducers. This GI-factor is a basic protein with an Mr of 25,000. Regulation by these protein factors together with other known cytokines of growth and differentiation of M1 cells is reported.

Animals↗
PubMed1989

Production of interleukin 6 and its relation to the macrophage differentiation of mouse myeloid leukemia cells (M1) treated with differentiation-inducing factor and 1 alpha,25-dihydroxyvitamin D3.

We have studied the production of interleukin 6 (IL-6) and its relation to the macrophage differentiation in murine myeloid leukemia cells (M1). As has been reported, differentiation-inducing factor (D-factor), 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3], and recombinant IL-6 similarly induced differentiation of M1 cells into macrophages. The three compounds also induced mRNA expression of IL-6 in M1 cells. M1 cells treated with D-factor or 1 alpha, 25(OH)2D3 produced biologically active IL-6, but the amounts of IL-6 secreted into culture media did not appear to be enough to induce differentiation of M1 cells. Furthermore, simultaneous addition of anti-IL-6 antibody did not suppress the differentiation of M1 cells induced by D-factor or 1 alpha, 25(OH)2D3. These results show that IL-6 production is an essential property associated with the macrophage differentiation of M1 cells, but it may not be responsible for the D-factor- and 1 alpha, 25(OH)2D3-induced differentiation.

Animals↗
PubMed1989

Antigenic determinants of the cytoplasmic domain of band 3 from bovine erythrocyte membrane.

Rabbit antibodies were prepared against the cytoplasmic 38K-Da fragment of bovine band 3 and the immunological cross-reactivity with human, murine, rat, and chicken band 3 was examined. The antibodies cross-reacted with human and rodent band 3, indicating that there is an antigenic determinant(s) common to primate and nonprimate species. However, the antibodies did not recognize chicken band 3. Antigenic sites on the 38K-Da fragment were determined via amino acid sequence and immunoblotting analyses of proteolytic peptides of the fragment. Positions of antigenic determinants which were assumed to be common to primate and nonprimate species were mapped to the areas of residues 127-160 and of residues 259-304 in the primary structure of human band 3. Another epitope(s), which is absent in human band 3, existed in a region having a bovine-specific amino acid sequence. In addition, comparison of sequence data from different species showed that a proposed hinge region and a tryptophan-rich region on the cytoplasmic domain of band 3 [P. S. Low et al. (1984) J. Biol. Chem. 259, 13,070-13,076; R. R. Kopito and H. F. Lodish (1985) Nature (London) 316, 234-238] are also conserved in the bovine case.

Amino Acid Sequence↗
PubMed1989

Contrasting effect of IFN-gamma and IFN-alpha/beta on differentiation of some clones of mouse myeloid leukemic cells.

Mouse myeloid leukemic M1 cells are induced to differentiate into macrophage-like cells by a differentiation-inducing factor (D-factor) and various agents. IFN-gamma alone did not induce differentiation of clone T22-3 of M1 cells but inhibited their differentiation by D-factor. That is, IFN-gamma at 4 U/ml inhibited 50% of phagocytic activity of T22-3 cells induced by 7 x 10(-11) M D-factor. In addition, it inhibited the induction of lysozyme activity and morphological differentiation of these cells by D-factor. IFN-gamma also inhibited dexamethasone-induced differentiation of T22-3 cells. Previously interferon-alpha/beta was shown not to induce differentiation of M1 cells itself, but to enhance induction of their differentiation by D-factor. The present study showed that IFN-alpha/beta and IFN-gamma had opposite effects on induction of differentiation of T22-3 cells by D-factor. The effect of IFN-gamma on the differentiation of M1 cells varied with the clone of M1 cells used: IFN-gamma inhibited D-factor-induced differentiation of cells of clones T22-3 and S2, but induced differentiation of cells of clones B24 and S1.

Animals↗
PubMed1989

Genomic cloning and heterologous expression of human differentiation-stimulating factor.

Differentiation-stimulating factor (D-factor) purified from mouse Ehrlich ascites cells was sequenced partially and found to be almost identical to leukemia inhibitory factor (LIF) from mouse Krebs II ascites cells. In comparison to LIF, D-factor had an additional amino-terminal serine residue. Using synthetic oligonucleotide probes designed from the murine D-factor sequence, we cloned the human gene encoding D-factor. A partial D-factor cDNA was cloned from COS-1 cells transfected with the human D-factor gene under the control of a heterologous promoter. We used this cDNA to construct a vector for direct expression of the protein in Escherichia coli. A mammalian cell expression vector was constructed using the signal sequence of interferon-alpha A linked to the D-factor cDNA. Both forms of recombinant human D-factor were active on the murine myeloid leukemia cell line M1 in a dose- and time-dependent manner for the inhibition of [3H]thymidine incorporation, and also induced phagocytosis, Fc receptor expression, and prostaglandin E2 synthesis by M1 cells.

Amino Acid Sequence↗
PubMed1989

Combined effects of differentiation-inducing factor and other cytokines on induction of differentiation of mouse myeloid leukemic cells.

Mouse myeloid leukemic M1 cells are induced to differentiate into macrophage-like cells by differentiation-inducing factors (D-factors) and granulocyte colony-stimulating factor. We examined the effects of recombinant human tumor necrosis factor (rTNF), lymphotoxin (rLT) and interleukin 1 (rIL-1) on the induction of differentiation of M1 cells, compared with the effects of D-factor purified from the conditioned medium of mouse Ehrlich ascites tumor cells and recombinant human granulocyte colony-stimulating factor (rG-CSF). rIL-1 induced phagocytic activity, a typical marker of cell differentiation, in at most 30% of M1 cells at concentrations ranging from 10(-10) M to 10(-7) M. The differentiation-inducing activity of rIL-1 was similar to that of rG-CSF and less than that of D-factor. rTNF induced phagocytic activity in 14% of M1 cells only at a high concentration (10(-7) M). rLT did not induce differentiation of the cells even at 10(-7) M. rTNF stimulated induction of differentiation of M1 cells by D-factor, rG-CSF or rIL-1 by two or three fold. The combination of any two of the cytokines D-factor, rG-CSF and rIL-1 induced differentiation of M1 cells more efficiently than any of these cytokines alone. Moreover, the combination of three cytokines rG-CSF, rIL-1 and rTNF, all of which are known to be produced by macrophages, was more effective than the combination of any two of these cytokines in induction of differentiation of M1 cells.

Animals↗
PubMed1988

Effect of stilbenedisulfonate binding on the state of association of the membrane-spanning domain of band 3 from bovine erythrocyte membrane.

The membrane-spanning domain of bovine band 3, the anion transport protein of erythrocyte membrane, was purified in the presence of nonaethyleneglycol lauryl ether (C12E9) and the effect of a covalent attachment of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS), a potent transport inhibitor, on the state of association of the domain isolated (the 58 kDa fragment) was studied via gel filtration, gel electrophoresis and sedimentation velocity experiments. It was indicated that the DIDS-unlabeled fragment in C12E9 solution forms heterogeneous aggregates which are larger in size than the dimer. This contrasted with the behavior that bovine band 3 is present as dimers or tetramers in the same medium (Nakashima and Makino (1980) J. Biochem. 88, 933-947). When DIDS was covalently attached, the fragment was present as a single molecular species which was indicated to be a dimer by molecular weight determination. The secondary structure of the fragment was not affected by DIDS. The change in the state of association caused by the DIDS-binding was also found in the presence of sucrose monolaurate (SE12), which was a more potent detergent for extraction of the 58 kDa fragment from membranes than C12E9. However, the complex with SE12 was extremely unstable.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1987

Mathematical model of Klebsiella pneumoniae resistance to amikacin and gentamicin.

1. The resistance of Klebsiella pneumoniae to amikacin and gentamicin was studied by a mathematical model to predict the rate of sensitivity decrease. The results accurately matched experimental data, showing that the model is a reliable predicting tool. 2. The observations were carried out over six years and included 2677 cultures that were positive for K. pneumoniae. At the beginning of the observation period, 85.7% of the cultures were sensitive to amikacin and 40.8% were sensitive to gentamicin. Sensitivity to amikacin showed a surprisingly rapid decrease; at the end of the experimental period, amikacin and gentamicin sensitivities were 33.3% and 27.8%, respectively. 3. We conclude that patterns of resistance of other bacteria could be investigated using this method.

Amikacin↗