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N Nara

Publications and source records attributed to N Nara.

At least 37 records · Page 2Linked to original sources
PubMed1996

Clonal involvement of eosinophils in therapy-related myelodysplastic syndrome with eosinophilia, translocation t(1;7) and lung cancer.

We report a therapy-related MDS (RAEB) patient with eosinophilia, unbalanced translocation der(7)t(1;7) (q12;q22) and lung cancer. We observed no increase in cytokine levels in serum or in the conditioned medium (CM) of peripheral T cells cultured with or without IL-2. When bone marrow (BM) cells were cultured with GM-CSF, IL-3 and SCF in a semisolid system, the colonies were exclusively eosinophilic. Cytogenetic analysis of the colony cells identified the same chromosome abnormality in all metaphases to that of BM cells. Suspension and clonogenic colony assay of BM cells cultured with various cytokines showed predominant eosinophilic growth and differentiation with GM-CSF, but not with the other cytokines examined. These findings, together with mild morphological abnormalities of eosinophils, indicate clonal involvement of eosinophils in the myelodysplastic syndrome (MDS) clone, and that the eosinophilia was derived from the neoplastic clone with the translocation and was not associated with the patient's lung cancer.

Aged↗
PubMed1996

Differential expression of CD44 splice variants in malignant and benign pleural effusions.

Expression of CD44 isoform that contains variant exons (v1-v10) has been implicated in tumor progression and metastasis. Especially, CD44 isoform containing v6 (CD44v6) and that containing v7 (CD44v7) were shown to confer full metastatic behavior on tumor cells. We examined the expression of CD44v6 and CD44v7 in malignant pleural effusions (13 lung cancers and 4 non-lung cancers) and in benign pleural effusions (7 tuberculosis and 3 pneumonia) with Southern blot analysis of reverse transcription (RT)-polymerase chain reaction (PCR) products. CD44v6 was expressed not only in malignant pleural effusions (12 of 13 lung cancers and 4 of 4 non-lung cancers), but also in benign pleural effusions(9/10). In contrast, although expression of CD44v7 was found in most malignant pleural effusions (12 of 13 lung cancers and 4 of 4 non-lung cancers), it was found in only a few cases of benign pleural effusions. These results suggest that the expression of CD44v7 may be correlated with a tumor-specific event such as metastasis or dissemination in malignant pleural effusion, while no such correlation can be found with CD44v6.

Alternative Splicing↗
PubMed1996

[Three cases of drug-induced hemolytic uremic syndrome].

We report three cases of drug-induced hemolytic uremic syndrome (HUS). Three patients with advanced gastrointestinal cancer underwent a curative operation and adjuvant chemotherapy with Mitomycin C (MMC), 5FU and Ara-C. Later, progressive anemia, thrombocytopenia, renal dysfunction and elevation of serum LDH were recognized. A diagnosis of HUS was made. As they had no symptoms of infectious diseases or relapse of cancer, the cause of HUS was thought to be MMC. Treatment with antiplatelet drugs and fresh frozen plasma was effective for two patients. However, one patient died of pulmonary edema.

Aged↗
PubMed1996

[Responses of cytokines, acute phase proteins, and polymorphonuclear cell elastase to surgical stress in the patients with esophageal cancer].

The serum levels of cytokines (interleukin-1 beta; IL-1 beta, interleukin-6; IL-6, tumor necrosis factor alpha; TNF alpha), and acute phase proteins (CRP, alpha 1-antitrypsin; alpha 1-AT, alpha 1-acid glycoprotein; alpha 1-AG, fibrinogen; FBG, pancreatic secretory trypsin inhibitor; PSTI), and the plasma concentration of polymorphonuclear cell elastase; PMN-E and white blood cell counts were measured in 18 patients with esophageal cancer who underwent radical esophagectomy through right thoracotomy and reconstruction with gastric tube. Peripheral venous blood samples were obtained before and just after operation, and on the 1st, 2nd, 3rd, 7th and 14th post-operative day. The serum concentrations of IL-6 just after operation were significantly correlated with volume of blood loss during operation and duration of thoracotomy. Plasma PMN-E levels just after operation seemed to be correlated with those factors, but its correlation was not statistically significant. Serum IL-6 levels began to increase markedly just after operation, and reached the maximum by the 1st post-operative day. This elevation preceded that of acute phase proteins, indicating that IL-6 may induce the production of acute phase proteins in vivo. Furthermore, peak serum values of IL-6 after operation were correlated with volume of blood loss and duration of thoracotomy. These results suggest that elevation of IL-6 and PMN-E levels may reflect the degree of surgical stress, and the measurement of IL-6 and PMN-E is useful for the early detection of an inflammatory response.

Acute-Phase Proteins↗
PubMed1995

Diversity and similarity in signaling pathways of hematopoietic growth factors in human leukemia cell lines.

Diversity and similarity in signaling pathways of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and stem cell factor (SCF) in five human factor-responsive leukemia cell lines were investigated by immunoblotting to detect tyrosine phosphorylation of intracellular proteins. G-CSF induced tyrosine phosphorylation of a set of proteins with few different components according to the cell lines. IL-3 also induced phosphorylation of several proteins. In a lymphoid cell line, phosphorylation patterns induced by IL-3 were somewhat different from that in myeloid cell lines. Phosphorylation patterns by G-CSF and those by IL-3 were similar in myeloid cell lines. In a cell line which responded to both IL-3 and SCF, almost similar sets of proteins were phosphorylated by each, although phosphorylation of a 92-KDa protein was specific to IL-3 and that of a 140-200-KDa protein was specific to SCF. Taken together, proliferative growth factors induced tyrosine phosphorylation of similar sets of proteins with little difference according to each growth factor and each target cell line.

Granulocyte Colony-Stimulating Factor↗
PubMed1995

The effect of basic and acidic fibroblast growth factors (bFGF and aFGF) on the growth of leukemic blast progenitors in acute myelogenous leukemia.

The effect of basic and acidic fibroblast growth factors on leukemic blast progenitors was studied in 14 patients with acute myelogenous leukemia and in one patient with chronic myelocytic leukemia in myeloid crisis. bFGF and aFGF stimulated blast-colony formation by leukemic blast progenitors cultured in methylcellulose in two patients. In the other 13 patients, no significant effect of either FGF on blast-colony formation was noted. The combination of bFGF or a FGF and G-CSF, GM-CSF, interleukin-3, or stem cell factor (SCF) had a synergistic effect on blast-colony formation in three patients. In the other patients, however, synergism between FGF and CSF was not detected. In fact, bFGF was found to suppress the stimulation of blast-colony formation due to GM-CSF in one of 10 patients and that due to SCF in four of eight patients. aFGF suppressed the stimulation of blast-colony formation due to GM-CSF in two of 11 patients and that due to SCF in four of eight patients. The results show that bFGF and aFGF do not directly play a major role in leukemic hematopoiesis but that they may modulate the cytokine network affecting leukemic cell growth.

Adult↗
PubMed1995

[N-acetyl-beta-D-glucosaminidase].

N-acetyl-beta-D-glucosaminidase (NAG), one of the glycolytic enzymes, is distributed in various tissue cells. Among them, the lysosome in the renal proximal tubular cells contains high amount of NAG. NAG is secreted in urine when kidney is damaged. Urinary NAG, therefore, is used as a marker which can detect the extent of the renal damage. Electrophoresis divides urinary NAG into three isozymes, pre A, A, and B forms. In normal males, the percentages of three isozymes are 12.3 +/- 5.56%, 73.15 +/- 4.77%, and 14.81 +/- 2.90%, respectively. In normal females, they are 12.87 +/- 4.70%, 65.47 +/- 4.61%, and 21.70 +/- 5.03%, respectively. The measurement of urinary NAG isozymes is useful to determine the type and severity of renal disease, especially renal tubular disease.

Acetylglucosaminidase↗
PubMed1995

[An abnormal hemoglobin which was found by chance at a health checkup].

A 68-year-old female visited our hospital because of low hemoglobin A1c content, which was found by chance at a health checkup. She did not have any symptom or sign except hypertension and low HbA1c. To determine the reason why HbA1c was so low in usual laboratory test, we carried out isoelectrofocusing (IEF) of the hemolysate, Hb instability test, and detection and isolation of the abnormal globin chain by urea CM-cellulose column chromatography. The abnormal beta-globin chain was digested with TPCK-trypsin, and the tryptic peptides were separated by HPLC on a reversed phase column. Finally the determination of amino acid composition and amino acid sequence of the abnormal peptide were performed. The Hb variant was identified as Hb Riyadh (beta 120Lys-->Asn). The detection and analysis of abnormal hemoglobin will be expected to increase in accordance with the increased opportunity of public health checkup.

Aged↗
PubMed1995

[Current and future approaches to therapy for multiple myeloma].

Multiple myeloma accounts for approximately 10% of hematologic cancers; it is characterized by an uncontrolled malignant growth of plasma cells occurring usually in the bone marrow or sometimes in other body sites as well. Malignant myeloma cells produce monoclonal immunoglobulins appearing as monoclonal spikes in the serum and/or urine. Patients with multiple myeloma suffer from various clinical features including bone destruction, bone marrow suppression, impaired renal function, hypercalcemia, serious infection, and amyloidosis. The combination of melphalan and prednisolone has been used as a standard therapy for this disease for over 30 years. The median survival of patients with multiple myeloma is 2.5-3 years, and only 10% of them survive longer than 10 years. To improve the prognosis for multiple myeloma, some strategies have been attempted. In this article, we introduce combination chemotherapy, interferon therapy, and bone marrow transplantation as newer approaches to therapy for multiple myeloma based on the biological characteristics of intractable multiple myeloma. Future therapeutic approaches are also discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Prognostic significance of the blast self-renewal capacity in patients with acute myeloid leukemia.

BACKGROUND: The proliferation of leukemic cells in acute myeloid leukemia (AML) is supported by a small subpopulation of leukemic blast progenitors, which can be detected in methylcellulose and suspension cultures. It is important to determine the association between the biologic properties of leukemic blast progenitors and the clinical prognosis of patients with AML. METHODS: Ninety-five patients with AML and two patients with chronic myelocytic leukemia in blast crisis were studied. T-cell depleted mononuclear cells obtained from the peripheral blood cells were cultured in both methylcellulose and suspension cultures. In methylcellulose culture, primary blast colony formation (PE1) and secondary blast colony formation (PE2) were enumerated. The recovery of clonogenic cells was determined in suspension culture. The association between PE1, PE2, or clonogenic cell recovery in suspension and the remission induction outcome or survival duration of the patients were examined. RESULTS: PE1 was not associated with the remission induction outcome. PE2 and clonogenic cells recovered in suspension were significantly associated with the remission induction. Furthermore, the survival duration of the patients who achieved complete remission was associated significantly with the number of clonogenic cells recovered in suspension. CONCLUSIONS: PE1 reflects the terminal divisions of leukemic blast progenitors, whereas PE2 and the recovery of clonogenic cells in suspension culture are considered to reflect the self-renewal of leukemic blast progenitors. The results suggest that the self-renewal capacity of leukemic blast progenitors is predictive of not only remission induction outcome but also survival duration of patients with AML.

Acute Disease↗
PubMed1994

Successful treatment of refractory pure red cell aplasia by buserelin acetate.

A 39-year-old female with autoimmune hemolytic anemia suffered from pure red cell aplasia. She received immunosuppressive agents including prednisolone, azathioprine, cyclophosphamide and methotrexate, resulting in a little improvement of the anemia for only short term. Consequently, she required multiple red cell transfusions for 3 years. She received buserelin acetate, a gonadotropin-releasing hormone analogue. Thereafter, the anemia dramatically improved. The direct effect of buserelin on hemopoietic progenitors was not detected in the in vitro culture study. It is most likely that buserelin enhanced erythropoiesis through the alteration of hormonal milieu. The usefulness of buserelin in the treatment of refractory pure red cell aplasia is discussed.

Adult↗
PubMed1993

Combined effect of interferon-gamma and tumor necrosis factor-alpha causing suppression of leukemic blast progenitors in acute myeloblastic leukemia.

The effects of interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha) on the growth of leukemic blast progenitors in 6 acute myeloblastic leukemia (AML) patients, 1 chronic myelocytic leukemia (CML) patient in blast crisis and a granulocyte colony-stimulating factor-(G-CSF-) dependent OCI/AML1a cell line established from an AML patient, were studied. Cells of fresh blood samples and the OCI-AML1a cell line were cultured in methylcellulose media and suspension culture in the presence of G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) supplemented as a growth stimulatory factor. Both cytokines suppressed the primary and secondary colony formation in methylcellulose culture of leukemic blast progenitors. The recovery of clonogenic cells in suspension culture was also suppressed by IFN-gamma and TNF-alpha. The primary colony formation in methylcellulose reflects the terminal divisions of leukemic blast progenitors, while the secondary colony formation in methylcellulose and the clonogenic cell recovery in suspension have been considered to reflect their self-renewal capacity. Therefore, IFN-gamma and TNF-alpha are considered to be effective in suppressing not only the terminal divisions but also self-renewal of leukemic blast progenitors. When both cytokines were added simultaneously to cultures, the suppressive effect of each cytokine was enhanced. The results may suggest the effectiveness of IFN-gamma and TNF-alpha in the treatment of leukemia.

Blast Crisis↗
PubMed1993

[The role of cytokines in the proliferation of leukemia cells in acute myelogenous leukemia].

Acute myelogenous leukemia is characterized by the infinite proliferation of malignant leukemia cells and by the impaired hematopoiesis. The proliferation of leukemia cells is supported by a small subpopulation, leukemic blast progenitors. Leukemic blast progenitors make leukemic blast colonies in methylcellulose culture. To determine the mechanism by which leukemia cells proliferate, we studied the role of several cytokines in the proliferation of leukemic blast progenitors in vitro. The findings indicated that there are at least three types in the regulation by cytokines of the leukemic cell growth. One is the stimulation of leukemic blast progenitors by colony-stimulating factors(CSFs) or interleukins(ILs) added in culture. These cytokines include granulocyte-CSF(G-CSF), granulocyte-macrophage CSF (GM-CSF), IL-3 and IL-1. The second is the autocrine growth mechanism. Leukemia cells by themselves produce and secrete G-CSF and GM-CSF, which stimulate the growth of leukemic blast progenitors. The third is a complex mechanism. IL-1, produced by leukemia cells or other cells, enhances the production of GM-CSF by leukemia cells, which stimulates the growth of leukemic blast progenitors. The precise mechanism by which each cytokine acts on leukemic blast progenitors should be determined to explore the mechanism of leukemia cell growth.

Cell Division↗
PubMed1993

Effects of stem cell factor (SCF) on the in vitro growth of leukemic blast progenitors in acute non-lymphocytic leukemia.

We studied the effects of recombinant human stem cell factor (SCF) on the growth of leukemic blast progenitors obtained from 27 acute non-lymphocytic leukemia (ANLL) patients and 1 chronic myelocytic leukemia patient in myeloid crisis; the effects varied among the patients. While SCF did not have stimulatory effects in the cells of 7 patients, it stimulated primary and secondary blast colony formation in methylcellulose culture and the recovery of clonogenic cells in suspension cultures from 21 patients. SCF stimulated leukemic blast progenitors in a manner almost comparable to or more prominently than that of other CSFs, namely, IL-3, GM-CSF, and G-CSF, in 9 patients. One patient responded to SCF but not to the other CSFs. In another 11 patients, SCF was less effective on leukemic blast progenitors than the other CSFs tested. To explain the variable effects of SCF, we investigated the relation between the phenotype of leukemic blasts and responsiveness to this agent; the response was significantly higher in patients with CD34-positive blasts than in those with CD34-negative blasts. These results imply that responsiveness to SCF differs among leukemic blast progenitors originating at different hematopoietic stages. In some ANLL patients, SCF showed synergy with other CSFs, suggesting that SCF may be involved in the cytokine network affecting leukemic hematopoiesis.

Adolescent↗
PubMed1993

[A clinical study on the efficacy of ceftazidime alone or in combination with aspoxicillin against infections in obstetric and gynecological patients].

We studied clinical effects of ceftazidime (CAZ) alone or in combination with aspoxicillin (ASPC) against various infections in obstetric and gynecological patients. 1. Obstetric and gynecological patients (n = 91) with various infectious diseases were treated with CAZ alone (1-2 g x 2/day, n = 54) or in combination with ASPC (1-2 g x 2/day, n = 37) administered via drip infusion. 2. CAZ alone or in combination with ASPC was efficacious in 50 out of 54 (92.6%) or 33 out of 36 (91.7%) patients, respectively. Overall, the efficacy ratios were 46/49 (93.9%) against gynecological infections, 21/25 (84.0%) against perinatal infections and 16/16 (100%) against other infections. The bacteriological efficacy ratio was 21/21 (100%) while clinical effectiveness in cases in which causative agents were known was observed in 20 out of 21 (95.2%) patients. In patients who had not respond to other treatments, CAZ alone, and in combination with ASPC were effective in 15 out of 16 (93.8%) and 6 out of 8 (75.0%) patients, respectively, hence the overall efficacy ratio was 21/24 (87.5%). 3. Abnormal values in clinical laboratory tests were obtained in 3 out of 91 (3.3%) patients. No other adverse side effects were observed in any of the patients.

Adult↗
PubMed1993

Growth potentiating activity of endogenous production of interleukin-1 and tumor necrosis factor alpha in blast cells of acute myeloblastic leukemia.

For the optimal growth of clonogenic cells in acute myeloblastic leukemia (AML), several cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and IL-6 are required in addition to colony-stimulating factor (CSF), which may be produced by blast cells themselves. In the present study, we addressed the potential role of endogenous production of TNF-alpha and/or IL-1 in the in vitro growth of AML clonogenic cells supported by IL-3. Addition of a specific neutralizing antibody against TNF-alpha (anti-TNF-alpha) to the culture significantly reduced the growth-stimulating effect of IL-3 on the cells in 11 of 14 patients. Simultaneous addition of anti-IL-1 alpha and anti-IL-1 beta also partly affected the growth, although to a much lesser extent when compared to the effect observed with anti-TNF-alpha. In 3 patients, the growth-stimulating effect of IL-3 was completely abrogated by anti-TNF-alpha or a combination of all three antibodies. Constitutive TNF-alpha transcript was observed in 5 patients and TNF-alpha protein was present in culture supernatant. Following in vitro culture, a transient but profound increase in c-fos, c-jun, TNF-alpha and IL-1 beta mRNA levels was observed. Anti-TNF-alpha inhibited the accumulation of TNF-alpha transcript, suggesting that membrane-integrated TNF-alpha may be partly responsible for the induction of TNF-alpha mRNA. It seems likely that the accumulation of these genes occurs through a protein kinase C-independent signaling pathway.

Antibodies↗
PubMed1993

Mixed colony formation composed of erythroblasts and myeloblasts by leukemic blast progenitors in patients with erythroleukemia.

To determine the clonal origin and growth requirement of leukemic blast progenitors in erythroleukemia, acute myelogenous leukemia (AML) M6, T cell-depleted mononuclear cells obtained from 5 erythroleukemia patients were cultured in methylcellulose media. Although plating efficiency did not significantly differ from those in the other AML subtypes, the morphology of colonies in erythroleukemia was distinct. Two types of colonies were formed; one was composed of myeloblasts, and the other consisted of erythroblasts and myeloblasts. The "mixed" colony formation was not stimulated by interleukin-3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor or erythropoietin. Both types of colonies were formed spontaneously in the absence of supplemented growth-stimulatory factor when cultured at high density. The results suggest that leukemic blast progenitors in erythroleukemia originated at the stage of bipotent hematopoietic precursor capable of differentiating into erythroid and myeloid lineages. The formation of mixed colonies composed of erythroblasts and myeloblasts in the absence of erythropoietin or colony-stimulating factor may indicate the deranged hematopoiesis in erythroleukemia.

Adult↗