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M Tomida

Publications and source records attributed to M Tomida.

At least 19 recordsLinked to original sources
PubMed1999

Cytoplasmic domains of the leukemia inhibitory factor receptor required for STAT3 activation, differentiation, and growth arrest of myeloid leukemic cells.

Leukemia inhibitory factor (LIF) induces growth arrest and macrophage differentiation of mouse myeloid leukemic cells through the functional LIF receptor (LIFR), which comprises a heterodimeric complex of the LIFR subunit and gp130. To identify the regions within the cytoplasmic domain of LIFR that generate the signals for growth arrest, macrophage differentiation, and STAT3 activation independently of gp130, we constructed chimeric receptors by linking the transmembrane and intracellular regions of mouse LIFR to the extracellular domains of the human granulocyte macrophage colony-stimulating factor receptor (hGM-CSFR) alpha and betac chains. Using the full-length cytoplasmic domain and mutants with progressive C-terminal truncations or point mutations, we show that the two membrane-distal tyrosines with the YXXQ motif of LIFR are critical not only for STAT3 activation, but also for growth arrest and differentiation of WEHI-3B D+ cells. A truncated STAT3, which acts in a dominant negative manner was introduced into WEHI-3B D+ cells expressing GM-CSFRalpha-LIFR and GM-CSFRbetac-LIFR. These cells were not induced to differentiate by hGM-CSF. The results indicate that STAT3 plays essential roles in the signals for growth arrest and differentiation mediated through LIFR.

Animals↗
PubMed1998

Postcontrast magnetic resonance imaging to predict progression of traumatic epidural and subdural hematomas in the acute stage.

OBJECTIVE: We investigated the possibility of predicting the progression of traumatic epidural hematomas (EDHs) and subdural hematomas (SDHs), in the acute stage, by using postcontrast magnetic resonance imaging (MRI) with gadolinium-diethylenetriaminepentaacetic acid. METHODS: From January 1990 through December 1996, 41 patients with 43 hematomas (21 EDHs and 22 SDHs) underwent postcontrast MRI within 24 hours after injury. T1-weighted MRI was performed by using the spin echo method, after the administration of 0.1 mmol/kg gadolinium-diethylenetriaminepentaacetic acid, immediately after computed tomographic scanning. RESULTS: All of the enhanced hematomas were enlarged, whereas nonenhanced hematomas, except for two SDHs with bleeding tendencies, remained unchanged or decreased in volume. The prediction rates for enlargement with this method were 100% (21 of 21) for EDHs and 91.0% (20 of 22) for SDHs. The sensitivity of this test in predicting enlargement was 100% (15 of 15) for EDHs and 81.8% (9 of 11) for SDHs. The specificity was 100% for both types of hematomas. The enlargement rates for diffusely enhanced hematomas were statistically greater than those for nonenhanced hematomas. All of the patients with diffusely enhanced hematomas, which were found during surgery to exhibit active bleeding points, experienced consciousness deterioration. CONCLUSION: We conclude that diffuse enhancement indicates extravasation from broken vessels that continue to bleed and that diffusely enhancing hematomas will be rapidly enlarged. We think that postcontrast MRI can be very useful for predicting the progression of acute EDHs and SDHs.

Acute Disease↗
PubMed1998

Plasma concentrations of brain natriuretic peptide in patients with subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Hyponatremia after subarachnoid hemorrhage (SAH) is commonly associated with diuresis and natriuresis, but the causes are still controversial. We investigated whether brain natriuretic peptide (BNP) was related to such hyponatremia. METHODS: Plasma BNP concentrations were measured by immunoradiometric assay in 18 patients at 0 to 2 days (period 1), 7 to 9 days (period 2), and > 14 days (period 3) after SAH. Plasma concentrations of antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), and noradrenaline were also measured during period 2. RESULTS: The 11 patients with hyponatremia (serum sodium concentration of < 135 mEq/L) had much higher plasma BNP concentrations during each period than did healthy controls (P < 0.05), whereas the 7 patients with normonatremia did not show statistically higher values. In the patients with hyponatremia, the plasma BNP concentration during period 2 was statistically higher than that during periods 1 and 3 (P < 0.05). The plasma noradrenaline concentration during period 2 was higher in patients with hyponatremia than in those with normonatremia (P < 0.05), whereas the plasma concentrations of ADH and ANP during period 2 were not statistically different between the hyponatremic and normonatremic patients. CONCLUSIONS: We conclude that BNP may be related to hyponatremia associated with natriuresis following SAH. The increase of noradrenaline may promote the secretion of BNP.

Acute Disease↗
PubMed1997

Presence of mRNAs encoding the soluble D-factor/LIF receptor in human choriocarcinoma cells and production of the soluble receptor.

Four different kinds of cDNAs encoding the receptor for the differentiation stimulating factor (D-factor)/leukemia inhibitory factor (LIF) were isolated from a human liver cDNA library. Three kinds of the cDNAs had different intronic sequences, which introduced a termination codon before the transmembrane domain. However, the site of insertion in human cDNAs is different from those in mouse cDNAs. Recombinant proteins produced by COS-7 cells after transfection of these cDNAs bound D-factor/LIF. mRNAs corresponding to these cDNAs are expressed by the human liver, placenta, and choriocarcinoma cell line NJG. In conditioned medium of choriocarcinoma cells, a native soluble receptor for the D-factor/LIF with a dissociation constant of 7.8 nM and a MW of 160 kDa was found.

Alternative Splicing↗
PubMed1996

Detection of in vivo differentiation of murine WEHI-3B D+ leukemia cells transfected with the lac-Z marker gene using two-color flow cytometry.

The in vivo induction of the differentiation of murine WEHI-3B D+ myelomonocytic leukemia cells was measured by flow cytometry, simultaneously staining leukemia cells for the marker exogenous beta-galactosidase and for differentiation by the antigen Mac-1 (CD11b/CD18). The WEHI-3B D+ leukemia cells were transfected with the E. coli lac-Z gene by electroporation and subclones that constitutively expressed high levels of the lac-Z gene product beta-galactosidase were established. Flow cytometric analyses of cells in the peritoneal cavities of mice bearing leukemia cells showed that cells continued to express beta-galactosidase for at least 14 days, and they were distinguishable from host-derived cells in vivo by their expression of the transfected gene. Simultaneous determination of the beta-galactosidase activity and Mac-1 content of cells in the peritoneal cavities of mice revealed that administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the mice enhanced the expression of Mac-1 antigen by beta-galactosidase-positive cells. The results demonstrate that G-CSF may have clinical potential as a therapeutic differentiating agent, and that flow cytometric analysis provides a useful in vivo system to evaluate the therapeutic potential of agents capable of inducing terminal differentiation.

Animals↗
PubMed1996

Structure of the gene encoding the human differentiation-stimulating factor/leukemia inhibitory factor receptor.

The human gene encoding the differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) receptor was cloned and its structure was analyzed. The gene spans more than 70 kilobases and contains 20 exons. The D-factor/LIF receptor can be subdivided into several regions; cytokine receptor homologous domain 1, an Ig-like domain, cytokine receptor homologous domain 2, three fibronectin type III domains, a transmembrane domain and a cytoplasmic region. Each domain of the receptor is encoded by a set of exons. There is a TATA sequence upstream of the transcription initiation site. One unit of the Alu sequence is present in the 5' flanking region. An NF-IL6 site is located 31 bases downstream of the transcription initiation site.

Base Sequence↗
PubMed1996

Glioblastoma multiforme in the left frontal lobe subsequent to malignant lymphoma in the right orbit.

A 62-year-old male presented with glioblastoma multiforme in the left frontal lobe manifesting as motor aphasia, subsequent to a malignant lymphoma in the right orbit. He underwent subtotal removal of the right orbital mass presenting as right exophthalmos which was shown by histological examination to be non-Hodgkin's lymphoma. He received 30 Gy Lineac irradiation to the right orbit. His post-operative course was satisfactory. Magnetic resonance (MR) imaging with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) 7 months later demonstrated a small spotty enhanced lesion in the left frontal lobe. He developed motor aphasia 1 year after irradiation. MR imaging disclosed an enhanced mass in the left frontal lobe, which was totally removed. Histological examination revealed glioblastoma multiforme. Patients with malignant lymphoma may develop a subsequent second malignant tumor. MR imaging with Gd-DTPA is quite useful for early detection of a second brain tumor.

Brain Neoplasms↗
PubMed1995

Induction of differentiation of WEHI-3B D+ leukemic cells transfected with differentiation-stimulating factor/leukemia inhibitory factor receptor cDNA.

Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor can induce the differentiation of mouse myeloid leukemia M1 cells and also stimulate proliferation of the interleukin-3 (IL-3)-dependent cell line, DA-1a. To determine whether D-factor can induce the differentiation of leukemia cells other than M1 cells, WEHI-3B D+ mouse myelomonocytic leukemia cells were transfected with a plasmid containing mouse D-factor receptor cDNA. Expression of D-factor receptor in transfected cells was determined by binding of [125]D-factor and analyzed by Scatchard's method. The transfected cells had high-affinity D-factor receptors with a dissociation constant of 100 to 200 pmol/L and binding sites per cell varied from 67 to 1,500 among several clones. The cells expressing a high level of D-factor receptor were induced to differentiate by D-factor; about 60% of the cells exhibited the ability to reduce nitroblue tetrazolium and expression of the differentiation antigen Mac-1 (CD11b) on the cell surface increased. The effect of cytokines, which induce the differentiation of M1 cells, on the transfected WEHI-3B cells was examined. The sensitivity to oncostatin M was identical to that against D-factor in the cells of each clone. Expression of D-factor receptor in WEHI-3B cells promoted sensitivity to IL-6 and granulocyte colony-stimulating factor (G-CSF). Induction of differentiation of the cells accompanied the suppression of proliferation. Treatment of the cells with D-factor for longer than 5 days resulted in 50% inhibition of growth. These results indicate that the stimulating effect of D-factor on the differentiation of malignant myeloid cells is not unique to M1 cells.

Animals↗
PubMed1995

Local structural difference between human and bovine band 3 in the anion transport inhibitor-binding region.

We have examined molecular properties of inhibitor-complexed human and bovine band 3, an anion transport protein of erythrocyte membrane, in order to demonstrate the structural characteristics of the inhibitor binding region. Band 3 modified with DIDS (4,4'-diisothiocyano-2,2'-stilbenedisulfonate), a potent anion transport inhibitor, generated a positive circular dichroic band at a wavelength of 345 nm, corresponding to a DIDS chromophore. The dichroic spectra of human band 3-DIDS complex and its bovine counterpart differed markedly in their ellipticity. Under the conditions that H2DIDS (the dihydro-derivative of DIDS) cross-linked two chymotryptic fragments of human band 3, the reagent failed to cross-link the equivalent bovine fragments. The inhibitory effect of PLP (pyridoxal 5'-phosphate), a substrate and affinity label, on phosphate influx into red blood cells was more pronounced for human band 3 than for bovine band 3. The residue Lys-562 of human band 3 was found to be modified with PLP, while the corresponding residue of bovine band 3 was devoid of reactivity with PLP.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Analysis of recombinant soluble mouse D-factor/LIF receptor.

The recombinant soluble mouse D-factor/LIF receptor (sD-factor-R) was expressed in COS-7 cells. Scatchard analysis of the bindings of mouse 125I-D-factor and human 125I-D-factor to the sD-factor-R indicated dissociation constants (Kd) of 12 and 0.267 nM, respectively, which were comparable to those of the binding protein in mouse serum. The apparent molecular masses of the sD-factor-R and human D-factor observed by gel filtration chromatography were 150 and 50 kDa, respectively. The size of the sD-factor-R.human D-factor complex was approximately 200 kDa, indicating that D-factor forms a 1:1 complex with the sD-factor-R. The sD-factor-R inhibited the induction of differentiation of mouse myeloid leukemic M1 cells by mouse D-factor by blocking the binding of this factor to the cells.

Animals↗
PubMed1994

Three different cDNAs encoding mouse D-factor/LIF receptor.

Three cDNAs for mouse differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) receptor were isolated from a cDNA library prepared from the liver of a pregnant mouse. A probe for screening was prepared by the RT-PCR method using human cDNA sequences as primers. The mouse D-factor receptor cDNA encoded 1,092 amino acids, which had a marked homology with the human counterpart and consisted of signal sequence, extracellular, transmembrane, and cytoplasmic domains. The WSXWS motif found in members of the cytokine receptor family was also present in the extracellular domain of the mouse D-factor receptor. A second form of cDNA that had a 501 bp insertion was isolated. The insertion introduced a stop codon so that the mRNA encoded the soluble receptor lacking transmembrane and intracellular domains. Because the insertion contained polyadenylation signals, two different sizes of mRNA encoding the soluble receptor were produced, depending on whether or not it utilized these signals. Transcripts utilizing these signals were 2.6-3 kb in size, and were very abundantly expressed in the liver. Transcripts that did not use these signals were longer than 5 kb and of similar size to the mRNA for the cellular receptor.

Amino Acid Sequence↗
PubMed1994

[Multiple sclerosis with syrinx formation in the spinal cord: a case report].

A 35-year-female developed tetraparesis following a period of back pain, urinary retension and paraparesis. She was admitted to our hospital on September 22, 1990. Neurological examination revealed tetraparesis with a sensory level at C3. Deep tendon reflexes were hyperactive in all four extremities with bilateral Hoffmann and Babinski reflexes. Spinal MR imaging demonstrated cavity formation within the cervical cord, extending from C2 to C6 without any anomalies at the craniocervical junction including Chiari malformation. The cavity was not enhanced with Gd-DTPA. Cerebrospinal fluid (CSF) examination revealed no abnormality. Although a syringo-subarachnoid shunt was performed on October 18, 1990, her symptoms did not improve. On December 17, 1990, she developed optic neuritis in the right eye and her paraparesis deteriorated. Delayed metrizamide CT scans showed another syrinx from Th3 to Th9. Repeated CSF contained 37 cells/mm3, protein 88 mg% and sugar 49 mg%. CSF oligoclonal bands were present and the CSF myelin basic protein was 6.6 ng/ml (normal < 4). A pulse therapy of steroid improved her vision and paraparesis. However, she developed paraparesis again on October 29, 1991. A brain T2-weighted MR image demonstrated multiple periventricular high signal intensity spots. Her paraparesis improved again with steroid. MR images in September, 1992 revealed a cord atrophy and disappearance of the cavity. Based on these clinical courses and radiological findings, a definite diagnosis of multiple sclerosis (MS) was made. We think MS may have caused the syringomyelia.

Adult↗
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↗