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N Nagata

Publications and source records attributed to N Nagata.

At least 91 records · Page 5Linked to original sources
PubMed1999

Role of CD14 expression in the differentiation-apoptosis switch in human monocytic leukemia cells treated with 1alpha,25-dihydroxyvitamin D3 or dexamethasone in the presence of transforming growth factor beta1.

Transforming growth factor beta (TGF-beta) enhanced the growth-inhibitory activities of dexamethasone (Dex) and 1alpha,25-dihydroxyvitamin D3 (VD3) on human monocytoid leukemia U937 cells. TGF-beta and VD3 synergistically increased the expression of differentiation-associated markers such as the CD11b and CD14 antigens, whereas TGF-beta and Dex did not. On the other hand, TGF-beta and Dex synergistically increased the number of Apo2.7-positive cells, which represents the early stage of apoptosis, whereas TGF-beta and VD3 did not, suggesting that TGF-beta enhanced apoptosis with Dex and enhanced monocytic differentiation with VD3. In the presence of TGF-beta, the retinoblastoma susceptibility gene product, pRb, was synergistically dephosphorylated by Dex as well as VD3. TGF similarly enhanced the expression of the p21Waf1 gene in U937 cells treated with Dex and VD3. TGF-beta dose-dependently increased the expression of Bcl-2 and Bad and decreased the expression of Bcl-X(L) in U937 cells. Dex enhanced the down-regulation of Bcl-X(L) expression in TGF-beta-treated cells, whereas VD3 blocked this down-regulation of Bcl-X(L). However, the down-regulation of Bcl-X(L) by treatment with the antisense oligomer did not affect the apoptosis or differentiation of U937 cells. The apoptosis of CD14-positive cells was suppressed in the VD3 plus TGF-beta-treated cultures. These results suggest that the expression of CD14 is involved in the survival of differentiated cells.

Apoptosis↗
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

Transforming growth factor-beta1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells.

Osteoclastogenesis inhibitory factor (OCIF), also termed osteoprotegerin (OPG), is a secreted member of the tumor necrosis factor (TNF) receptor family. It inhibits bone resorption in vivo and osteoclast-like cell (OCL) formation in vitro. To better understand the biological role of OCIF, we first examined the effects of various osteotropic agents on OCIF mRNA levels in mouse calvarial osteoblasts. Northern blot analysis showed that stimulators of OCL formation such as 1,25-(OH)2D3, prostaglandin E2 (PGE2), parathyroid hormone (PTH), and interleukin 1 (IL-1) decreased OCIF mRNA levels. In contrast, transforming growth factor (TGF)-beta1 increased OCIF mRNA levels in primary osteoblasts as well as in osteoblastic/stromal cell lines. Since it was reported that both TGF-beta1 and OCIF not only inhibited OCL formation but also impaired the survival of OCL by inducing apoptosis in vitro, we next examined the possible involvement of OCIF in TGF-beta1-induced impairment of OCL survival. In a mouse bone marrow culture, we confirmed that addition of OCIF or TGF-beta1 decreased the number of surviving OCL. Anti-OCIF IgG, which completely neutralized the effect of OCIF, partially prevented the TGF-beta1-induced decrease in the number of OCL. Our results suggest that (i) downregulation of OCIF expression is one of the mechanisms for the stimulatory effects of 1,25(OH)2D3, PGE2, PTH, and IL-1 on osteoclastogenesis; and (ii) the TGF-beta1-induced apoptosis of OCL is mediated, at least in part, by upregulation of OCIF expression.

Animals↗
PubMed1998

Osteoclastogenesis inhibitory factor suppresses osteoclast survival by interfering in the interaction of stromal cells with osteoclast.

Osteoclastogenesis inhibitory factor (OCIF) was originally identified as a factor inhibiting osteoclast (OC) formation. The number of OC in rats treated with OCIF decreased, suggesting that OCIF inhibits OC formation in vivo; however, it is also possible that OCIF affects the number of OC by promoting apoptosis of OC. To address this issue, the effects of OCIF on the survival of OC were examined using well established mouse culture systems. OCIF dose-dependently inhibited OC formation in mouse marrow cultures. Addition of OCIF during day 0-3 did not alter the peak levels of OC formation on day 7 and 8. However, the addition of OCIF during day 5 and thereafter resulted in the rapid decrease of the number of OC. OCIF inhibited the survival of OC formed in mouse marrow cultures in dose- and time-dependent manners. The involvement of stromal cells in OC survival was examined using crude and stromal cell-depleted OC populations. OCIF dramatically inhibited the survival of crude OC populations rich with stromal cells. However, in stromal cell-depleted OC populations, OC spontaneously decreased in the absence of OCIF and OCIF did not enhance the decrease further at least up to 48 h. Apoptotic OC were detected in detached cell populations treated with OCIF in mouse marrow cultures and a specific inhibitor for caspase-3 rescued the death of OC. OCIF mutant lacking the death domain homologous regions inhibited OC survival, though the potency was much less than native OCIF. Taken together, OCIF inhibited not only OC recruitment but also OC survival. OCIF inhibited OC survival by interfering the interaction of stromal cells with OC.

Animals↗
PubMed1998

Alzheimer's disease with asymmetric parietal lobe atrophy: a case report.

A 52-year-old, right-handed female presented with visuospatial dysfunction including left hemineglect, incomplete Balint's syndrome, and environmental agnosia, together with left-sided motor symptoms such as unskillful movement, dystonic postures, and myoclonus in the left hand, without significant dementia. Symptoms progressed to akinetic mutism prior to her death 10 years after onset of illness. Imaging studies such as MRI, SPECT, and PET studies showed severe, predominantly right-sided involvement of parietal and parieto-occipital areas. The motor signs might originate from the right parietal lesions such as area five or somatosensory area. Neuropathologic studies including immunocytochemistry showed tau-positive neurofibrillary tangles and abundant neuritic plaques with amyloid deposits, confirming the diagnosis of Alzheimer's disease. An analysis of serum apolipoprotein E revealed epsilon3/epsilon3 homozygosity. This case represents a variant of Alzheimer's disease conspicuous for progressive motor signs and visuospatial dysfunction with a striking laterality, reflecting asymmetric parietal involvement. Alzheimer's disease with asymmetric parietal atrophy is difficult to be clinically distinguished from corticobasal degeneration characterized by progressive unilateral motor signs and focal cortical signs.

Agnosia↗
PubMed1998

Enhancement of metastatic activity of colon cancer as influenced by expression of cell surface antigens.

BACKGROUND: Cell surface antigens are contributory factors toward metastatic activity. There have been no detailed studies on changes in cell surface antigens of colon cancer cell lines. To control life-threatening metastasis, it is necessary to evaluate what types of changes in cell surface antigens exert an influence on metastatic activity. MATERIALS AND METHODS: In vivo selection was performed using the human colon cancer-derived cell line KM12SM to obtain variants of metastatic activity. A murine spleen injection-liver metastasis procedure reflecting the latter half of the metastatic process was adopted and repeated four times. Flow cytometric analyses were carried out to detect expression of antigens: Lewis a (Lea), Lewis x (Lex), sialyl Lewis a (sLea), sialyl Lewis x (sLex), E-cadherin, CD44v6, integrin alpha2 (CD49b), integrin alpha3 (CD49c), integrin alpha4 (CD49d), integrin alpha5 (CD49e), and integrin beta1 (CD29). RESULTS: In vivo selection produced variants with higher metastatic activity. In the original line KM12SM, sLea, E-cadherin, CD49b, CD49c, or CD29 were positive in more than 40% of the cells. After selection, the percentage of cells positive for Lea, sLea, and all examined integrins significantly increased. Lex, sLex, and CD44v6 increased slightly, while E-cadherin decreased slightly. CONCLUSIONS: In vivo selection and flow cytometric analysis revealed that Lea, sLea, CD49b, CD49c, and CD29 appear to be involved in the increase of metastatic activity. The changes of integrin expression in this study suggest that integrins collaborate in the promotion of adhesion to an extracellular matrix.

Animals↗
PubMed1998

A case of pulmonary reaction with skin eruption showing a positive peripheral lymphocyte stimulation test result for ethambutol.

We report a case of an elderly male whose pulmonary reaction with skin eruption occurred in the initial phase of chemotherapy composed of isoniazid, rifampicin, and ethambutol (EB). A peripheral lymphocyte stimulation test (LST) showed a positive reaction only to EB. The blood serum analysis of the patient when this reaction occurred revealed an elevated titer of antinuclear antibody. Computed tomography (CT) scan films of the chest when the pulmonary reaction occurred showed multifocal subpleural consolidations. There has been only one reported case of EB-induced pulmonary reaction and its clinical course was very similar to ours. However, LST results and computed tomography (CT) scan findings of the chest were not documented in that case.

Aged↗
PubMed1998

Evaluation by multivariate analysis of the differentiation inhibitory factor nm23 as a prognostic factor in acute myelogenous leukemia and application to other hematologic malignancies.

The differentiation inhibitory factor nm23 can inhibit the differentiation of murine and human myeloid leukemia cells. We recently reported that nm23 genes were overexpressed in acute myelogenous leukemia (AML), and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML, especially in AML-M5 (acute monocytic leukemia). To evaluate the importance of nm23 expression as a prognostic factor in AML, we compared it with other putative prognostic factors in AML. An analysis of the correlation between nm23 expression and the clinical parameters of 110 patients with AML demonstrated that increased nm23-H1 mRNA levels were associated with resistance to initial chemotherapy and with reduced overall survival. Multivariate analysis using Cox's proportional hazard model also showed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. Especially in AML-M5, nm23-H1 status was the most important prognostic factor. Furthermore, to determine whether we can apply the results observed in AML to other hematologic malignancies, we investigated the relative levels of nm23-H1 and nm23-H2 transcripts in 149 patients with hematologic neoplasms, including 110 with de novo AML, 9 with de novo acute lymphoblastic leukemia, 14 with myelodysplastic syndrome, 16 with chronic myelogenous leukemia (CML), and 5 normal subjects by the reverse transcriptase-polymerase chain reaction. Expression of nm23-H1 was significantly higher in all the hematologic neoplasms, except CML in chronic phase, than in normal blood cells. nm23 may have a prognostic effect in these hematologic malignancies as well as in AML.

Acute Disease↗
PubMed1998

The effect of exhaustive exercise on the antioxidant enzyme system in skeletal muscle from calcium-deficient rats.

The aim of the current study was to elucidate the synergism of dietary calcium restriction and exhaustive exercise in the antioxidant enzyme system of rat soleus muscle, and to investigate the involvement of neutrophils in exercise-induced muscle damage. Forty-eight male Wistar rats were assigned to the following groups: control (C) or calcium-restricted [1 month (1 M) or 3 months (3 M)]. Each group was subdivided into acutely exercised or non-exercised groups. Soleus muscle from each rat was analysed to determine the levels of antioxidant enzymes [Mn-superoxide dismutase (SOD), Cu, Zn-SOD, glutathione peroxidase (GPX), and catalase (CAT)]. Dietary calcium restriction resulted in calcium deficiency and upregulated the antioxidant enzymes examined except GPX. Conversely, exhaustive exercise significantly decreased GPX and CAT, but not SODs activities in the calcium-restricted (1 M and/or 3 M) rats. Contents of immunoreactive Mn-SOD and Cu,Zn-SOD were only increased in the 3 M rats. During calcium restriction, the mRNA expression of both forms of SOD showed initial upregulation, followed by downregulation. Exhaustive exercise significantly increased the mRNA expressions only in the 3 M rats. Moreover, exhaustive exercise markedly increased myeloperoxidase activity in soleus muscles from the 1 M and 3 M rats compared with the C rats, and significantly enhanced the ability of neutrophils to generate superoxide in the 3 M rats. The results demonstrate that dietary calcium restriction upregulates certain antioxidant enzyme activities in rat soleus muscle, indicating an enhanced resistance to potential increases in intracellular reactive oxygen species. The results also suggest that exhaustive exercise may cause oxidative damage in soleus muscle of calcium-deficient rats through the activation of neutrophils.

Animals↗
PubMed1998

Right ventricular obstruction by tricuspid pouch in simple ventricular septal defect.

Tricuspid pouch sometimes causes subpulmonary obstruction in association with transposition of the great arteries, but rarely does so without transposition. A 5-year-old girl with isolated ventricular septal defect exhibited dynamic right ventricular outflow tract obstruction caused by pouches in the anterior and septal tricuspid leaflets. Echocardiography clearly demonstrated features of the tricuspid pouches. Ventricular septal defect closure resulted in disappearance of the tricuspid pouches and resolution of subpulmonary obstruction.

Child, Preschool↗
PubMed1998

Anastomosis of the left juxtaposed atrial appendages in a patient with tricuspid atresia.

A 9-month-old boy with left juxtaposition of the atrial appendages, tricuspid atresia, pulmonary atresia, and ventriculoarterial discordance underwent anastomosis between the atrial appendages after failure of balloon/blade atrial septostomy because of restrictive atrial septal defect. For surgical creation of atrial communication in patients with juxtaposed atrial appendages, anastomosis between the atrial appendages seemed to be safer, more effective, and less invasive than septectomy by Blalock-Hanlon technique or inflow occlusion technique.

Anastomosis, Surgical↗
PubMed1998

Effect of acarbose on postprandial lipid metabolism in type 2 diabetes mellitus.

The effect of acarbose, an alpha-glucosidase inhibitor, on postprandial glucose and lipid metabolism was investigated in patients with type 2 diabetes mellitus. Twenty patients (10 men and 10 women) with type 2 diabetes mellitus were studied. A test meal was taken with or without 100 mg of acarbose. The levels of plasma glucose, and serum immunoreactive insulin, lipids, apolipoproteins, and remnant-like particle cholesterol were investigated. Acarbose inhibited the postprandial increase of both plasma glucose and serum immunoreactive insulin. Acarbose also significantly suppressed the increase of serum triglycerides at 60, 90, and 120 min (P < 0.05 to P < 0.01), and the increase of serum remnant-like particle cholesterol at 60 and 120 min (P < 0.05). Acarbose inhibited the postprandial decline of apolipoprotein C-II, and decreased the postprandial serum apolipoprotein C-III level. These results suggest that acarbose may improve postprandial hyperlipidemia as well as postprandial hyperglycemia in patients with type 2 diabetes mellitus.

Acarbose↗
PubMed1998

Elevated expression of differentiation inhibitory factor nm23 mRNA in monoblastic crisis of a patient with chronic myelogenous leukemia.

Differentiation inhibitory factor nm23 gene has been found to be expressed in high quantities in acute myelogenous leukemia (AML), especially in acute monocytic leukemia (AML-M5) and is suggested as a new prognostic factor in AML-M5. We report an example of elevated expression of nm23 mRNA in a patient with chronic myelogenous leukemia (CML) who developed monoblastic crisis. Relative levels of nm23-H1 and -H2 mRNA extracted from the patient's peripheral blood mononuclear cells and bone marrow mononuclear cells were measured by quantitative reverse transcriptase polymerase chain reaction. The level of nm23-H1 mRNA in CML cells at the chronic phase was as high as that in bone marrow cells from healthy volunteers. The mRNA level of nm23-H2 was slightly below the normal level. At blastic crisis, however, expression of both nm23-H1 and -H2 mRNA was elevated to about three to nine times of that at the chronic phase. Proliferated blastic cells were positive for non-specific esterase, and the serum lysozyme level was elevated and diagnosed as monoblastic crisis. The patient received combined chemotherapy but response was partial. These findings are compatible with our previous report that nm23 gene is overexpressed in monocytic leukemia.

Antigens, Neoplasm↗
PubMed1998

Mouse mammary carcinoma cell line (BALB/c-MC) stimulates osteoclast formation from mouse bone marrow cells through cell-to-cell contact.

We recently reported that numerous osteoclasts (OC) were formed in cocultures of some mouse cancer cell lines and bone marrow cells. In this study, we examined mechanisms by which one of the cell lines, BALB/c-MC, induces OC. BALB/c-MC dose dependently stimulated OC formation in cocultures. In cocultures where direct cell-to-cell contact between BALB/c-MC and bone marrow cells was inhibited by membrane filters, OC formation was not stimulated. The stimulation of OC formation in the coculture was completely abolished by adding 10(-7)-10(-6) mol/L indomethacin. The concentration of prostaglandin E2 (PGE2) in the culture media of cocultures with cell-to-cell contact was higher than that of cocultures without cell-to-cell contact or marrow cultures alone, and it reached levels sufficient to induce OC (11.9 +/- 5.3 ng/mL [about 3.4 x 10(-8) mol/L]). When BALB/c-MC or bone marrow cells were fixed with formalin and then cocultured with bone marrow cells or BALB/c-MC, respectively, the concentration of PGE2 in the culture media of cocultures of fixed BALB/c-MC and bone marrow cells increased, whereas that of cocultures of BALB/c-MC and fixed bone marrow cells did not increase. These results indicate that BALB/c-MC stimulate OC formation through direct cell-to-cell contact with bone marrow cells, and PGE2 released from bone marrow cells through direct cell-to-cell contact are involved in OC formation by the cell line.

Animals↗
PubMed1998

Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy.

Osteoclastogenesis inhibitory factor (OCIF) is a novel secreted protein that inhibits osteoclastogenesis both in vitro and in vivo. In this study, we examined the effects of OCIF on serum calcium (Ca) concentrations in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. In normal mice, a single intraperitoneal injection of OCIF reduced serum Ca levels in a dose-dependent manner. Significant decrease in serum Ca (by 1.6 +/- 0.3 mg/dL, n = 5) was observed 2 h after the injection of OCIF at 20 mg/kg and the hypocalcemic effect continued for up to 12 h. Serum phosphate (Pi) concentrations also decreased in response to OCIF. Urinary excretion of Ca, Pi, and creatinine did not change significantly after injection of OCIF or vehicle. In hypercalcemic, tumor-bearing nude mice, a single intraperitoneal injection of OCIF at 20 mg/kg resulted in a dramatic decrease in serum Ca (maximal decrease 2.8 +/- 0.37 mg/dL, n = 11), which continued for up to 24 h. The results suggest that OCIF decreased serum Ca through its inhibitory effect on bone resorption. Furthermore, it is suggested that OCIF has therapeutic potential for the treatment of hypercalcemic conditions such as malignancy-associated hypercalcemia.

Animals↗