Biomedical subjects

Y Honma

Publications and source records attributed to Y Honma.

At least 37 records · Page 2Linked to original sources

PubMed2001

Induction of differentiation of human myeloid leukemia cells by immunosuppressant macrolides (rapamycin and FK506) and calcium/calmodulin-dependent kinase inhibitors.

OBJECTIVE: Potent immunosuppressants, such as rapamycin, FK506, and ascomycin, are known to regulate the phosphorylation of proteins. The purpose of this study was to investigate the effects of these immunosuppressants on differentiation of several human myeloid leukemic cell lines. MATERIALS AND METHODS: Human myeloid leukemic cell lines were cultured with each immunosuppressant, and several differentiation markers were assayed. RESULTS: Rapamycin effectively induced granulocytic differentiation of human myeloid leukemic HL-60 and ML-1 cells. In addition to morphologic differentiation, it also induced nitroblue tetrazolium reduction, lysozyme activity, and expression of CD11b in HL-60 cells. The commitment to differentiation was observed after treatment with rapamycin for 1 day, indicating that the effect of rapamycin was irreversible. FK506 and ascomycin induced differentiation of HL-60 cells, but at higher concentrations than rapamycin. A calcium/calmodulin-dependent kinase (CaMK) was copurified with FKBP52 immunophilin, a binding protein of immunosuppressants. We also found that the CaMK inhibitors KN62 and KN93 induced differentiation of HL-60 cells. Rapamycin and CaMK inhibitors induced differentiation of human myeloid leukemia ML-1 and K562, but not of other cell lines such as NB4, U937, or HEL. CONCLUSION: Immunosuppressants and CaMK inhibitors induced differentiation of HL-60, ML-1, and K562 cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2001

Serum nm23-H1 protein as a prognostic factor for indolent non-Hodgkin's lymphoma.

Standard chemotherapy has been ineffective for improving the poor 10-year survival rate of patients with indolent lymphoma. However, a wider choice of therapeutic modalities has become recently available, including immunotherapy with monoclonal antibodies and allogeneic peripheral blood stem cell transplantation. Accordingly, a sensitive prognostic indicator is required to identify high-risk patients and to help design new therapeutic approaches for them. We previously reported that the serum nm23-H1 protein level was an independent prognostic factor for aggressive lymphoma. The present study was performed to assess the clinical implications of this protein on indolent lymphoma and whether it can be used to classify the aggressiveness of the disease in order to assist in the individualization of therapy. A total of 130 patients with indolent lymphoma were enrolled in this multicenter study. The serum nm23-H1 protein level was significantly higher in patients with indolent lymphoma than in a normal control group. In addition, indolent lymphoma patients with higher nm23-H1 levels had worse overall and progression-free survival rate than those with lower nm23-H1 levels. Therefore, nm23-H1 in serum may be useful for identifying a distinct group of patients at high risk.

Adolescent↗

PubMed2001

Sensitization by 5-aza-2'-deoxycytidine of leukaemia cells with MLL abnormalities to induction of differentiation by all-trans retinoic acid and 1alpha,25-dihydroxyvitamin D3.

Most chromosomal abnormalities associated with breakage at 11q23 in acute leukaemia involve the MLL gene, and the presence of this breakage strongly predicts a poor clinical outcome. We assessed the possibility of differentiation-inducing therapy for acute leukaemias with chromosomal translocations involving 11q23. Among the cell lines with MLL translocations that we examined, KOCL48 and KOPN-1 cells were induced to differentiate into granulocytes by all-trans retinoic acid (ATRA) or into monocytes by 1alpha,25-dihydroxyvitamin D3 (VD3). These cells expressed p16 mRNA before treatment with 5-aza-2'-deoxycytidine (5-AZA), an inhibitor of DNA methylation. On the other hand, differentiation was not induced in SN-1, KOCL33, KOCL51 or KOCL44 cells by ATRA or VD3, and these cells did not express mRNA of this gene. However, these cells were effectively induced to differentiate by ATRA or VD3 in the presence of 5-AZA, and concomitantly exhibited p16 gene expression, suggesting an association between DNA demethylation and restoration of sensitivity to differentiation-inducing activity of ATRA or VD3 in leukaemia cells with MLL abnormalities. Based on these findings, combined treatment with ATRA or VD3 plus 5-AZA may be clinically useful in therapy for acute leukaemia with MLL abnormalities.

Antimetabolites, Antineoplastic↗

PubMed2001

Induction of the monocytic differentiation of myeloid leukaemia cells by cotylenin A, a plant growth regulator.

Regulators that play an important role in the differentiation and development of plants or invertebrates may also affect the differentiation of human leukaemia cells through a common signal transduction system, and might be clinically useful for treating acute myeloid leukaemia. Cotylenin A has been isolated as a plant growth regulator. We examined the effects of cotylenin A on the differentiation of several myelogenous leukaemia cells, and found that cotylenin A is a potent and novel inducer of the monocytic differentiation of human myeloid leukaemia cells. Cotylenin A induced the functional and morphological differentiation of myeloblastic and promyelocytic leukaemia cells, but did not effectively induce the differentiation of monocytoid leukaemia cells. Cotylenin A-induced differentiation was not affected by several inhibitors of signal transduction, suggesting that this inducer exhibits a unique mode of action.

Androstadienes↗

PubMed2001

Differentiation of human acute myeloid leukaemia cells in primary culture in response to cotylenin A, a plant growth regulator.

Cotylenin A, which has a diterpenoid tricarbocyclic skeleton, has been isolated as a plant growth regulator, has been shown to affect several physiological processes of higher plants and have differentiation-inducing activity in several myeloid leukaemia cell lines. We examined the effect of cotylenin A on the differentiation of leukaemic cells that were freshly isolated from acute myeloid leukaemia (AML) patients in primary culture. Cotylenin A significantly stimulated both functional and morphological differentiation of leukaemia cells in 9 out of 12 cases. This differentiation-inducing activity was more potent than those of all-trans retinoic acid and 1alpha,25-dihydroxyvitamin D3 (VD3). Treatment with a combination of cotylenin A and VD3 was more effective than cotylenin A or VD3 alone at inducing the monocytic differentiation of AML cells.

Acute Disease↗

PubMed2001

Enhanced anti-Shigella activity of erythromycin supplemented with sulfadiazine.

Sulfadiazine enhanced the anti-Shigella activity of erythromycin. Erythromycin passes through the type III secretion apparatus and suppresses the growth of invasive Shigella organisms. Sulfadiazine enhanced this effect at the concentration under minimum inhibitory concentration and it came from not only the folate-inhibiting activity but also from a new function. It has proved that sulfadiazine stimulated type III secretion in Shigella as determined from the secretion of the pathogenic protein IpaB. As Congo red induced secretion of Ipa proteins and uptake of erythromycin through the type III secretion gate, sulfadiazine which is similar to Congo red in chemical structure may induce the uptake in the same way.

Animals↗

PubMed2001

[Effective use of electrolized soft acid aqueous solution for treatment of mediastinitis following cardiac surgery].

Mediastinitis following cardiac surgery occurs infrequently, but features both high mortality and morbidity, especially in patients with an artificial graft. A 24-year-old man was admitted with a diagnosis of Williams'syndrome with supraaortic stenosis. After ascending aorta and hemiarch reconstruction, mediastinitis developed, which was treated successfully with mediastinal irrigation using electrolized soft acid aqueous solution at one liter per day for 3 days. This procedure appears to be an effective method for treatment of mediastinitis following cardiac surgery.

Adult↗

PubMed2001

[Telangiectatic focal nodular hyperplasia: a case report].

Focal nodular hyperplasia(FNH) is a benign tumor-like lesion of the liver. The telangiectatic type is an atypical histologic variant of FNH, and descriptions of its radiologic findings are rare. We report a case of telangiectatic FNH. A 26-20 mm round lesion was found in the lateral segment of the liver. Although this lesion appeared similar to cavernous hemangioma with rapid intratumoral contrast material enhancement on cross-sectional images, its signal intensity decreased on T2-weighted imaging after the administration of superparamagnetic iron oxide(SPIO), and its appearance differed from that of cavernous hemangioma.

Diagnosis, Differential↗

PubMed2000

Redox properties and coordination structure of the heme in the co-sensing transcriptional activator CooA.

The CO-sensing transcriptional activator CooA contains a six-coordinate protoheme as a CO sensor. Cys(75) and His(77) are assigned to the fifth ligand of the ferric and ferrous hemes, respectively. In this study, we carried out alanine-scanning mutagenesis and EXAFS analyses to determine the coordination structure of the heme in CooA. Pro(2) is thought to be the sixth ligand of the ferric and ferrous hemes in CooA, which is consistent with the crystal structure of ferrous CooA (Lanzilotta, W. N., Schuller, D. J., Thorsteinsson, M. V., Kerby, R. L., Roberts, G. P., and Poulos, T. L. (2000) Nat. Struct. Biol. 7, 876-880). CooA exhibited anomalous redox chemistry, i.e. hysteresis was observed in electrochemical redox titrations in which the observed reduction and oxidation midpoint potentials were -320 mV and -260 mV, respectively. The redox-controlled ligand exchange of the heme between Cys(75) and His(77) is thought to cause the difference between the reduction and oxidation midpoint potentials.

Alanine↗

PubMed2000

Adjuvant action of Escherichia coli enterotoxin for delayed-type hypersensitivity to Oka vaccine virus on pernasal co-administration in mice.

The usefulness of a mutant of Escherichia coli enterotoxin for the induction of cellular immunity to varicella-zoster virus as a mucosal adjuvant is assessed in mice. When a commercially available live varicella vaccine (the Oka strain) and toxin were once administered simultaneously via the nasal route, delayed-type hypersensitivity to Oka vaccine virus was significantly induced and detected by footpad test in mice. Moreover, when spleen cells from mice immunized with the vaccine and toxin were re-stimulated with live vaccine in vitro, they showed more thymidine uptake and produced more IL-2 than those from mice immunized with the vaccine alone. These results suggest that mutant enterotoxin has adjuvant action to induce a specific delayed-type hypersensitivity to Oka vaccine virus on nasal co-administration with live vaccine virus.

Adjuvants, Immunologic↗

PubMed2000

Antileukemic efficacy of 2-deoxycoformycin in monocytic leukemia cells.

2'-Deoxycoformycin (dCF) as a single agent has been reported to be less effective against myeloid than against lymphoid malignancies in clinical trials. However, previous studies have shown that in the presence of 2'-deoxyadenosine (dAd), human monocytoid leukemia cell lines are much more sensitive to dCF with regard to the inhibition of cell proliferation. Thus, dCF might be useful for treating monocytoid leukemia with the aid of dAd analogs. The antiproliferative effects of dCF in combination with dAd or its derivatives were examined on normal and malignant blood and bone marrow cells. In the presence of 10 micromol/L dAd, the concentration of dCF required to inhibit the viability of primary monocytoid leukemia cells was much lower than that required to inhibit normal or non-monocytoid leukemic cells. Among the dAd analogs, 9-beta-D-arabinofuranosyladenine (AraA) was also effective in combination with dCF. Athymic nude mice were inoculated with human monocytoid leukemia U937 cells and treated with dCF or a dAd analog or both. Although dCF alone slightly but significantly prolonged the survival of mice inoculated with U937 cells, combined treatment with dCF and AraA markedly prolonged their survival. These data suggest that the combination of dCF and AraA may be useful for the clinical treatment of acute monocytic leukemia. (Blood. 2000;96:1512-1516)

Animals↗

PubMed2000

Plasma levels of the differentiation inhibitory factor nm23-H1 protein and their clinical implications in acute myelogenous leukemia.

A previous study reported that a nondifferentiating myeloid leukemia cell line produced differentiation-inhibiting factors. One of the factors was purified as a homologue of the nm23 genes. The nm23 genes were overexpressed in acute myelogenous leukemia (AML) cells, and a higher level of nm23 gene expression was correlated with a poor prognosis in AML. The present study determined the plasma levels of nm23-H1 protein by enzyme-linked immunosorbent assay and assessed the association between this level and the clinical outcome in 102 patients with AML. The plasma concentration of nm23-H1 was higher in patients with AML than in normal controls (P =.0001). Plasma nm23-H1 levels were correlated with the product of the intracellular nm23 messenger RNA (mRNA) level and the white blood cell count, but not with the mRNA level alone. Therefore, nm23-H1 plasma levels probably depend on the total mass of leukemic cells overexpressing the nm23-H1 gene. Overall survival was lower in patients with higher plasma nm23-H1 levels than in those with lower levels. Multivariate analysis using the Cox proportional hazard model showed that elevated plasma nm23-H1 levels significantly contributed to the prognosis of AML patients. Furthermore, the plasma nm23-H1 levels were investigated in 70 patients with other hematologic neoplasms, including 6 with acute lymphoblastic leukemia, 13 with chronic myelogenous leukemia, and 12 with myelodysplastic syndrome. Plasma nm23-H1 levels were significantly higher in all of these hematologic neoplasms than in normal controls. Increased plasma levels of nm23-H1 may have prognostic value in these hematologic malignancies as well as in AML.

Adult↗

PubMed2000

Humoral immunoresponse to varicella-zoster virus pernasally coadministered with Escherichia coli enterotoxin in mice.

It is evaluated whether Escherichia coli enterotoxin is useful for induction of immunity to varicella-zoster virus (VZV) as a mucosal adjuvant in mice. When a commercially available live varicella vaccine (Oka strain) and toxin were administered simultaneously via a nasal route three times at 2 or 6 month intervals, an antibody neutralizing VZV was detected in half or all of the mice vaccinated, respectively. The antibody specific to the vaccine strain of VZV reacted to five proteins, molecular weights of which were 110 K, 100 K, 62 K, 54 K and 46 K. These proteins were composed of glycosylated products of all kinds of glycoproteins. These results suggest that although a nasal administration of the vaccine without the adjuvant has little immunogenicity in mice, the simultaneous administration of the live vaccine and the toxin over a long period induces a specific humoral immunity to VZV.

Adjuvants, Immunologic↗

PubMed2000

SN-1, a novel leukemic cell line with t(11;16)(q23;p13): myeloid characteristics and resistance to retinoids and vitamin D3.

The MLL gene is fused with the cAMP-responsive element binding protein-binding protein (CBP) gene in t(11;16)(q23;p13), which has been reported to be associated with therapy-related acute leukemia. We established a novel myeloid cell line, SN-1, from a patient with T-cell acute lymphoblastic leukemia with t(11;16)(q23;p13) having in-frame MLL-CBP fusion transcripts. The majority of the SN-1 cells were positive for myeloperoxidase when examined using an electron microscope and expressed CD13, CD33, CD56, and HLA-DR antigens, but not CD7, CD10, CD19, CD34, or CD41 antigens, suggesting that these cells are of myeloid origin. SN-1 cells underwent functional and morphological differentiation when treated with actinomycin D or sodium butyrate, but not with all-trans-retinoic acid (ATRA) or 1alpha,25-dihydroxyvitamin D3 (VD3). Exposure of SN-1 cells to ATRA hardly affected cell growth and differentiation, whereas the growth of HL-60 and NB4 cells treated with ATRA was effectively inhibited, and differentiation into mature granulocytes was induced. SN-1 cells were relatively insensitive to VD3 with respect to inhibiting the cell growth and inducing the ability to reduce nitroblue tetrazolium, lysozyme activity, and morphological differentiation, although the expression of CD11b was slightly induced by VD3. These results suggest that the cell line was impaired in the signal transduction systems of ATRA and VD3. This cell line should be useful for the study of the role of CBP as a transcriptional regulator in leukemia differentiation and for the functional analysis of the MLL-CBP fusion gene, which will provide new insights into leukemogenesis caused by 11q23 translocations.

Amino Acid Sequence↗

PubMed2000

Myeloid and monocytoid leukemia cells have different sensitivity to differentiation-inducing activity of deoxyadenosine analogs.

The differentiation-inducing effect of clinically applicable analogs of deoxyadenosine on myelomonocytic leukemia cells was examined. Monocytoid leukemia cells were more sensitive to the analogs than were erythroid or myeloid leukemia cells based on the inhibition of cell growth and induction of cell differentiation. Monocytoid leukemia cells were highly sensitive to combined treatment with 2'-deoxycoformycin (dCF) and 9-beta-D-arabinofuranosyladenine (Ara A) for inducing cell differentiation. Ara A induced the differentiation of monocytoid leukemia U937 and THP-1 cells at concentrations which were 1/1000-10000 of that at which it induced the differentiation of other cell lines in the presence of dCF. In combination with a low concentration of 1alpha,25-dihydroxyvitamin D3 (VD3), the induction of the monocytic differentiation was greater in monoblastic U937 cells. Adenosine deaminase-resistant analogs such as fludarabine (FLU) and cladribine (CdA) also induced the differentiation of human myelomonocytic leukemia cells, and these analogs synergistically enhanced the differentiation induced by all-trans retinoic acid (ATRA) or VD3. CdA was the most potent analog for inducing the differentiation of myeloid leukemia NB4 and HL-60 cells in the presence or absence of ATRA. These findings indicate that dCF + Ara A and CdA may be effective for the therapy of acute monocytoid and myeloid leukemia, respectively.

Acute Disease↗

PubMed2000

CO sensing and regulation of gene expression by the transcriptional activator CooA.

The transcriptional activator CooA from Rhodospirillum rubrum contains a six-coordinate protoheme that acts as a CO sensor in vivo. CO is a physiological effector of CooA and replaces one of the axial ligands of the ferrous heme to form the CO-bound CooA that is active as the transcriptional activator. Cys75 or His77 is coordinated to the ferric and ferrous hemes in CooA, respectively. The redox-controlled ligand exchange between Cys75 and His77 proceeds during the change in the redox state of the heme. The reduction and oxidation midpoint potentials of CooA have been determined to be -320 and -260 mV, respectively. The properties of a functional chimera derived from CRP and CooA suggest that CooA activates the transcription by a similar mechanism to that for CRP at Class II CRP-dependent promoters. Alanine-scanning mutagenesis has revealed that Arg24 and Arg53 of CooA, which will be concerned with the protein-protein interaction with RNA polymerase, are critical amino acid residues for the transcriptional activator activity of CooA, and that Lys26 and Asp94 modulate the activity of CooA.

Bacterial Proteins↗

PubMed2000

Induction of apoptosis in lymphoid tissues of mice after intramuscular injection of enterotoxigenic Escherichia coli enterotoxin.

Although it has been reported that intravenous injection of Escherichia coli enterotoxin induces atrophies of the thymus and spleen by necrosis, the toxin injected intramuscularly to mice induced atrophies of both tissues, which were associated with apoptosis of lymphocytes. Apoptosis predominantly occurred in the thymus and increased in a time-dependent manner up to 26 h and faint ladder band patterns of DNA were observed at 36 h. Although the high dose of toxin also induced in vitro apoptosis in cultured thymocytes, the toxin was not detected in the serum at levels sufficient to cause in vitro apoptosis after intramuscular administration. By flow cytometric analysis, CD4+ CD8+ double-positive T cell and CD45+ positive B cell numbers were found to be mainly decreased in thymus and spleen, respectively, of mice. These results suggest that the atrophies of thymus and spleen by intramuscular administration of the toxin to mice are due to apoptosis of CD4+ CD8+ double-positive T and CD45+ positive B cells, respectively, but the toxin does not reach these cells via the circulation. A different mechanism from that in vitro in cultured cells might be involved in the induction of apoptosis in vivo.

Adjuvants, Immunologic↗

PubMed2000

Treatment of arteriovenous malformation of the brain--preliminary experience.

With the availability of new techniques, such as intravascular embolisation and radiosurgery, the therapeutic approach to arteriovenous malformations (AVMs) of the brain has recently been modified. The present study reports the authors, experiences in treating AVMs over the past 13 years. Spetzler-Martin grading of AVMs was I and II in 19 cases, III in 12, IV in 5 and V in 1 case. Four therapeutic regimens were utilised: surgical resection alone, embolisation and resection, and radiosurgery alone or after surgical resection. Generally, for low-grade AVMs (Spetzler-Martin grades I, II and III), the therapeutic choice was surgical resection in 27 cases, in combination with pre-operative embolisation in two of these patients. Two cases received radiotherapy only and one case received radiosurgery after embolisation, while one case was treated conservatively. Of the five cases of grade IV, four required surgical treatment, whereas the fifth case was treated conservatively. Favourable results (good recovery and moderate disability) were obtained in 96% of the low-grade AVMs as compared with the high-grade AVMs (66%) that had a poor outcome (due to primary brain damage resulting from haemorrhage at the onset in three cases and due to postoperative re-bleeding in one case). This report summarises preliminary experience in treating intracranial AVMs by surgical resection, intravascular embolisation and radiotherapy. Good therapeutic results can be expected by combining these therapeutic modalities.

Adult↗