Biomedical subjects

N Nara

Publications and source records attributed to N Nara.

At least 55 records · Page 3Linked to original sources

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

Comparison of the proliferative activity and sensitivity to cytosine arabinoside of leukemic blast progenitors in acute myeloblastic leukemia at diagnosis and in relapse.

To determine whether the biological characteristics of leukemic cells change after repeated chemotherapy, we compared the proliferative activity and drug sensitivity of leukemic blast progenitors in 7 patients with acute myeloblastic leukemia at diagnosis and in relapse. The proliferative activity of leukemic blast progenitors was assessed based on primary (PE1) and secondary (PE2) colony formation in methylcellulose culture and on the recovery of clonogenic cells in suspension culture. The effect of cytosine arabinoside (Ara-C) on leukemic blast progenitors was studied both in methylcellulose and in suspension cultures. PE1 and PE2 values varied among the patients. PE2 of 4 patients out of 7 patients became significantly higher in relapse than at diagnosis. The sensitivity to Ara-C of leukemic blast progenitors deteriorated in 5 patients in relapse. The results suggest that the biological nature in terms of proliferative activity and Ara-C sensitivity of leukemic blast progenitors may change in the clinical course after chemotherapy.

Blast Crisis↗

PubMed1992

Interleukin-6 reduces the optimal growth in vitro of leukemic blast progenitors from acute myeloblastic leukemia patients.

The combined effects of five cytokines; recombinant human (rHu) granulocyte colony-stimulating factor (G-CSF), rHu granulocyte-macrophage colony-stimulating factor (GM-CSF), rHu interleukin-1 beta (IL-1 beta), rHu interleukin-3 (IL-3), and rHu interleukin-6 (IL-6) on blast colony formation in methylcellulose by leukemic blast progenitors from 10 patients with acute myeloblastic leukemia (AML) were studied. Combination of G-CSF, GM-CSF, IL-1 beta, and IL-3 stimulated maximum blast colony formation in 9 patients. Further addition of IL-6 reduced the combined effect of the four cytokines on blast colony formation. IL-6 regulates the proliferation of leukemic blast progenitors and may play an important role in the regulation of hematopoiesis.

Bone Marrow↗

PubMed1992

Pure red cell aplasia following autoimmune haemolytic anaemia. Cell-mediated suppression of erythropoiesis as a possible pathogenesis of pure red cell aplasia.

We report here a rare case of pure red cell aplasia (PRCA) following autoimmune haemolytic anaemia (AIHA). After 4 years of AIHA, the patient developed anaemia with severe erythroid hypoplasia and was diagnosed as having PRCA. At this time, Coombs' test was negative and parvovirus infection was not recognized. The patient received azathioprine, and PRCA improved. To determine the pathogenesis of PRCA, in vitro culture studies of erythropoietic and granulopoietic precursors were performed. The patient's serum or IgG did not suppress the colony formation of bone marrow colony-forming units-erythroid (CFU-E) of normal subjects and the patient. In contrast, mononuclear cells in the peripheral blood of the patient significantly suppressed CFU-E of normal subjects. Media conditioned by the patient's mononuclear cells did not significantly suppress CFU-E. The significant production of suppressive cytokine such as tumour necrosis factor or gamma-interferon by the patient's mononuclear cells was not recognized. These findings suggest that the cytotoxic mononuclear cells affected directly the erythropoietic precursors and caused PRCA in this patient. The pathogenesis of PRCA was, therefore, considered to be different from that of the preceding AIHA.

Adult↗

PubMed1992

Enhanced effect of mutant granulocyte-colony-stimulating factor (KW-2228) on the growth of normal and leukemic hemopoietic progenitor cells in comparison with recombinant human granulocyte-colony-stimulating factor (G-CSF).

We tested the in vitro effect of a novel granulocyte colony-stimulating factor (G-CSF) derivative (KW-2228) on the growth of G-CSF-dependent hemopoietic progenitor cells: granulocyte precursor cells (CFU-G), leukemic blast progenitors freshly obtained from 9 patients with acute myeloblastic leukemia (AML) and cells of a G-CSF-dependent human AML cell line (OCI/AML 1a). KW-2228 showed a higher stimulating effect than recombinant human G-CSF (rhCSF) on CFU-G; 3 out of 9 leukemic blast progenitors and OCI/AML 1a cells. The difference in biochemical stability between rhG-CSF and KW-2228 was considered to explain the superior colony-stimulating activity of KW-2228. The results show that KW-2228 will be a new granulopoietic factor.

Amino Acid Sequence↗

PubMed1992

Colony-stimulating factor (CSF)-dependent growth of two leukemia cell lines.

The progressive accumulation of leukemic cells in acute myeloblastic leukemia (AML) results from the self-renewal capacity of leukemic blast progenitors. The growth of leukemic blast progenitors is supported by growth factors and colony-stimulating factors (CSFs) have been shown to stimulate this phenomenon in vitro. After repeated subculture of leukemic cells obtained from a patient with AML M4 in the presence of recombinant G-CSF, a cell line dependent on G-CSF was established. This cell line, designated OCI/AML1a, does not respond to GM-CSF, interleukin-3 (IL-3), IL-1 or stem cell factor as well as G-CSF. The stimulatory effect of G-CSF on OCI/AML1a cells is almost completely blocked by monoclonal anti-G-CSF antibody. With G-CSF added in the culture, the OCI/AML1a cell line has been growing exponentially for over 5 years now. Another cell line, with growth dependent on IL-3, has also been established from a patient with chronic lymphocytic leukemia in the acute phase. This cell line TMD2 does not respond to G-CSF, GM-CSF, IL-1, or stem cell factor and anti-IL-3-antibody blocks the stimulatory effect of IL-3 on these cells. Receptors for IL-3 have been found on the surface of TMD2 cells. Although the TMD2 cell line is not derived from AML, the novel character of IL-3-dependency provides useful information for the study of the role of growth factor(s) in leukemic cell proliferation. These two CSF-dependent cell lines are expected to be excellent models for the investigation of the precise mechanism by which G-CSF and IL-3 stimulate the growth of leukemic cells.

Aged↗

PubMed1992

[Diagnosis on Mycoplasma pneumoniae infections by DNA-probe assay in comparison with serological tests].

To evaluate the usefulness of DNA diagnosis as a diagnostic approach to Mycoplasma pneumoniae infections, we compared the DNA-probe assay with serological tests in 32 patients who were clinically suspected of having Mycoplasma pneumonia. The DNA-probe assay was carried out using the Gen-probe kit. Serological tests included complement fixation and passive hemagglutination tests. At first visit 10 patients were positive for the DNA-probe assay, while only 2 of them were positive for serological tests. The other 3 patients became positive for serological tests during the clinical course. In accordance with clinical improvement, these patients became negative for the DNA-probe assay. Three patients were negative for DNA-probe assay while they were positive for the serological tests. However, these patients had already received antibiotics; therefore, their conditions were considered to have been improved at the time of the study. The other 19 patients were negative for both the DNA-probe assay and serological tests. These patients might have suffered from respiratory tract infections of pathogenic organisms other than M. pneumoniae or the number of M. pneumoniae might have been too small to be detected by the DNA-probe assay. The results of the present work demonstrate that the DNA-probe assay was valuable in the diagnosis of mycoplasmal infections at the early stage, which indicates that DNA diagnosis provides useful information to determine the most appropriate therapeutic regimen.

Child↗

PubMed1992

[Clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology].

The efficacy and safety of imipenem/cilastatin sodium (IPM/CS) were studied in patients with obstetric and gynecologic infections and in those given the drug as prophylaxis against postoperative infections. The following results were obtained: 1. Efficacy rates were 96.0% (48/50) in patients with obstetric and gynecologic infections and 100% (28/28) in those with urinary tract or other infections. The overall efficacy rate was 97.4% (76/78). Bacteriologically, 30 organisms were isolated from 28 patients. The eradication rate was 95.2% (20/21) and the efficacy rate was 96.4% (27/28). 2. Changes in blood elastase before and after treatment were compared with those in CRP, WBC, and ESR in the patients with obstetric and gynecologic infections. The changes in elastase were similar to those in CRP. 3. The efficacy rate was 98.0% (48/49) in the patients given prophylaxis against postoperative obstetric and gynecologic infections. 4. An adverse reaction was observed in only one patient (diarrhea), and abnormal laboratory findings were noted in 2 patients (elevation of GOT and GPT). These results indicate that IPM/CS is very useful for the treatment of obstetric and gynecologic infections.

Adolescent↗

PubMed1992

Detection of myeloid precursors (granulocyte/macrophage colony forming units) in the bone marrow adjacent to rheumatoid arthritis joints.

Various cytokines were recently found to be involved in the pathogenesis of rheumatoid arthritis (RA) and particularly, cytokines with hematopoietic activity have been detected in synovial tissues. We counted the number of myeloid precursors in terms of granulocyte/macrophage colony forming units (CFU-GM) and the number of stromal cell progenitors in terms of fibroblast colony forming units (CFU-F) in the tibial bone marrow adjacent to the joints affected by RA (n = 21), osteoarthritis (OA) (n = 10), and trauma (n = 2) using the colony formation unit assay. We also quantitated the amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony stimulating factor (GM-CSF) in the culture supernatant of synovial tissue explants of these patients by enzyme linked immunosorbent assay (ELISA). The mean number (+/- SEM) of CFU-GM in patients with RA (7.4 +/- 4.9) was greater than that in patients with OA (0.5 +/- 0.2), while CFU-GM was not detected in trauma patients. The number of CFU-GM in the tibial bone marrow of patients with RA correlated well with the amount of IL-1 beta (r = 0.64, p < 0.01), but not with GM-CSF or with IL-6 from synovial tissues. These findings suggest that active bone marrow is present adjacent to the affected joints in patients with RA and that hematopoietic activity is influenced by IL-1 beta produced in nearby synovial tissues.

Aged↗

PubMed1992

[Lymphomatoid granulomatosis (LYG) occurring in a patient with follicular lymphoma during remission].

A 49 years-old man presented with dry cough, low grade fever, and abnormal shadow on a chest X-ray. He had suffered from follicular lymphoma of the liver 5 years previously. He received irradiation therapy in combination with chemotherapy for approximately three years and had been in complete remission. Physical and radiological examination revealed pleural effusion and softly dense masses in the right lung. The laboratory data were within normal limits. He was diagnosed as having lymphomatoid granulomatosis (LYG) by open lung biopsy. The lung lesion was mainly infiltrated with T cells. The patient received prednisolone and the lung lesions disappeared. However, when a lung mass was noted two months later, he started to receive combination chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, and prednisolone every three months. He has not shown relapse of LYG so far. To investigate the association between the preceding follicular lymphoma and subsequent LYG at this time, DNA analysis using the PCR technique was carried out. The LYG lesion did not show a rearranged band for the JH probe, while the paraffin-embedded specimen of the preceding follicular lymphoma had shown rearranged band for the JH band. Southern blot analysis of the LYG lesion, showed no rearrangement for TCR beta, gamma or JH probe. These findings indicate that the LYG was different from the preceding follicular lymphoma in terms of origin. LYG is considered to be induced in the immunosuppressive state due to lymphoma.

Combined Modality Therapy↗

PubMed1992

The in vitro growth patterns and drug sensitivities of leukemic blast progenitors among the subtypes of acute myelocytic leukemia.

The in vitro growth activities and drug sensitivities of leukemic blast progenitors were compared among the subgroups of acute myelocytic leukemia (AML) classified according to the French-American-British (FAB) cooperative group. Leukemic cells separated from the peripheral bloods of AML patients were cultured in methylcellulose media, and the plating efficiencies of primary colonies (PE1) and secondary colonies after replating (PE2) were determined. PE1 and PE2 have been considered to reflect the capacities of terminal divisions and self-renewal of leukemic blast progenitors, respectively. PE1 and PE2 were variable among AML patients; these findings suggest that AML is a heterogeneous disease in terms of the proliferative activities of leukemic cells. No significant correlation was noted between PE1 or PE2 and the AML subtype. The sensitivities to cytosine arabinoside (Ara-C) of leukemic blast progenitors were studied in methylcellulose and suspension cultures. Ara-C sensitivity was not significantly correlated with the AML subtype, either. In contrast, there was statistically significant correlation between PE2 and the remission outcome of the patients, whereas PE1 was not significantly associated with the clinical outcome. The results in the present study indicate that the proliferative activity, especially self-renewal capacity, of leukemic blast progenitors is highly predictive of the prognosis of AML patients but is not significantly correlated with the AML subtype classified by the blast morphology.

Adolescent↗

PubMed1991

Establishment of an interleukin-3-dependent leukemic cell line from a patient with chronic lymphocytic leukemia in the acute phase.

A novel human leukemic cell line, TMD2, which proliferates dependently on interleukin-3 (IL-3), was established from the peripheral blood (PB) of a patient with chronic lymphocytic leukemia (CLL) in the acute phase. After 8 years of the chronic phase of CLL, lymphoblastoid cells appeared and became dominant in the PB. After repeated subcultures of the patient's PB cells in the acute phase, lymphoblastoid cells have proliferated actively in the presence of recombinant human IL-3, and the TMD2 cell line has been established. The lymphoblastoid cells in acute phase and TMD2 cells proliferated dependently on IL-3, whereas growth of the small lymphocytes in chronic phase was not supported by IL-3. Other ILs (IL-1, 2, and 4 through 6) or CSF did not support the growth or survival of TMD2 cells. The existence of high-affinity receptors for IL-3 was shown on TMD2 cells (binding sites 88 per cell, Kd = 76.9 pmol/L). DNA extracted from the small lymphocytes in the chronic phase, the lymphoblastoid cells in the acute phase, and TMD2 cells showed the same rearrangement pattern of the immunoglobulin heavy-chain gene. Therefore, these cells were considered to have originated from the same clone. These results imply that a genetic event that caused the responsiveness to IL-3 in the cell of the chronic phase caused the acute transformation of CLL in this patient. We consider that TMD2 cell line is valuable as a model of cells of CLL in the acute phase and as a tool for studying the signal transduction system of IL-3.

Aged↗

PubMed1991

Antiproliferative and differentiative effects of recombinant interleukin-4 on a granulocyte colony-stimulating factor-dependent myeloblastic leukemic cell line.

The effect of recombinant human interleukin-4 (IL-4) on a granulocyte colony-stimulating factor (G-CSF)-dependent human myeloblastic leukemic cell line, OCI-AML1a, was investigated. IL-4 suppressed the clonogenic cell growth in methylcellulose culture, inhibited the uptake of 3H thymidine in a dose-dependent manner at 5 to 100 U/mL, and consequently suppressed the growth of clonogenic cells in short- and long-term suspension cultures. In addition, IL-4 markedly increased the number of adherent cells. These adherent cells were alpha-naphthyl-butyrate (alpha-NB) esterase-positive and showed macrophage-like appearance, increased expression of CD14, CD11b, CD23, and Ia, and significantly decreased clonogenicity. On the other hand, nonadherent cells growing in suspension showed only slight increase in proportion of alpha-NB esterase-positive or monocyte/macrophage-like cells and increased CD23 expression by an addition of IL-4. The clonogenicity of the nonadherent cells was not significantly influenced by IL-4. By addition of the media conditioned by OCI-AML1a cells in the presence of IL-4, the clonogenic cells growth of OCIAML1a cells was suppressed and adherent cells were markedly increased. The suppressive and differentiative effects on OCI/AML1a cells of the conditioned media and IL-4 itself were almost completely abolished by anti-IL-4 antibody. Furthermore, the neutralizing antibodies against transforming growth factor-beta 2 (TGF-beta 2), tumor necrosis factor-alpha (TNF-alpha), or IL-6 did not influence the effect of recombinant IL-4. Taken together, IL-4 was shown to suppress the growth and induce differentiation toward adherent macrophage-like cells of the G-CSF-dependent myeloblastic cell line. The effect of IL-4 may be direct, and not secondary via inducing production of other cytokines such as TGF-beta, TNF-alpha, or IL-6 by leukemic cells.

Cell Adhesion↗

PubMed1991

Enhancement by transforming growth factor-beta 1 (TGF-beta 1) of the proliferation of leukemic blast progenitors stimulated with IL-3.

We studied the effect of transforming growth factor-beta 1 (TGF-beta 1) on colony formation of leukemic blast progenitors from ten acute myeloblastic leukemia (AML) patients stimulated with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), interleukin-6 (IL-6), or interleukin-1 beta (IL-1 beta). These CSFs and interleukins by themselves stimulated the proliferation of leukemic blast progenitors without adding TGF-beta 1. G-CSF, GM-CSF, and IL-3 stimulated blast colony formation in nine patients, IL-6 stimulated it in five, and IL-1 beta stimulated in four. TGF-beta 1 significantly reduced blast colony formation stimulated by G-CSF, GM-CSF, or IL-6 in all patients. In contrast, TGF-beta 1 enhanced the stimulatory effect of IL-3 on blast progenitors from three cases, while in the other seven patients TGF-beta 1 reduced blast colony formation in the presence of IL-3. To study the mechanism by which TGF-beta 1 enhanced the stimulatory effect of IL-3 on blast progenitors, we carried out the following experiments in the three patients in which it occurred. First, the media conditioned by leukemic cells in the presence of TGF-beta 1 stimulated the growth of leukemic blast progenitors, but such effect was completely abolished by anti-IL-1 beta antibody. Second, the addition of IL-1 beta in the culture significantly enhanced the growth of blast progenitors stimulated with IL-3. Third, leukemic cells of the two patients studied were revealed to secrete IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) constitutively; the production by leukemic cells of IL-1 beta and TNF-alpha was significantly promoted by TGF-beta 1. Furthermore, the growth enhancing effect of TGF-beta 1 in the presence of IL-3 was fully neutralized by anti-IL-1 beta antibody. These findings suggest that TGF-beta 1 stimulated the growth of blast progenitors through the production and secretion of IL-1 beta by leukemic cells.

Aged↗

PubMed1991

Effects of recombinant interleukin 4 on the growth and differentiation of blast progenitors stimulated with G-CSF, GM-CSF and IL-3 from acute myeloblastic leukaemia patients.

The effects of human recombinant interleukin 4 (rIL-4) on the growth of leukaemic blast progenitors were investigated. Cells obtained from 20 acute myeloblastic leukaemia (AML) patients were evaluated using the blast colony assay in methylcellulose and suspension cultures. While rIL-4 by itself did not show any colony stimulatory activity in the blast colony assay, it suppressed the blast colony formation in methylcellulose stimulated with G-CSF, GM-CSF or IL-3 in 14 patients. In another six patients, rIL-4 enhanced blast colony growth in four patients or did not show any significant effect with any CSF in two patients. In suspension cultures of 12 cases studied, the effects of rIL-4 on the clonogenic cell recoveries were essentially similar to the results of the blast colony assay in each case. In three patients, rIL-4 augmented the differentiation of the leukaemic cells to monocyte lineage. Further, the clinical outcome was significantly different between the patients whose blast progenitors were stimulated by rIL-4 and the patients whose blast progenitors were suppressed by rIL-4 (P less than 0.05); three out of four patients in the former group failed in achieving complete remission (CR), while 12 out of 14 patients in the latter group achieved CR. The results show that the effects of IL-4 on leukaemic blast progenitors were diverse and the responsiveness to IL-4 may be correlated with the prognoses of the patients.

Acute Disease↗

PubMed1991

[Evaluation of DNA-probe assay for the clinical diagnosis of Mycoplasma pneumoniae infections].

DNA probe-assay using the Gen-Probe kit was carried out to detect Mycoplasma pneumoniae infections. Fifteen children visited Ota General Hospital complaining of dry cough and high grade fever. Throat swabs of the patients were examined to detect M. pneumoniae ribosomal RNA by Gen-Prove kit. Five out of 15 patients were positive for DNA probe assay of M. pneumoniae. Clinical and laboratory data including serological examinations were compatible with M. pneumoniae infection in these cases. Following the improvement of clinical symptoms and signs by receiving erythromycin or minocycline, the positivity for DNA probe assay turned to negative. Among the ten patients, who were negative for DNA probe assay, 2 cases were suspected of M. pneumoniae infection on the basis of clinical and laboratory findings. One patient had already taken antibiotics. Therefore, in these two patients, there was a possibility that the bacterial numbers were too small to be detected by DNA-probe assay. The data described above support that DNA-probe assay is useful for the diagnosis of M. pneumoniae infections in the early stage. DNA-probe assay is also valuable to follow up the clinical course of the patients.

Child↗

PubMed1991

Effect of protein kinase inhibitors on the proliferation of leukemic cells stimulated by granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor or interleukin-3.

The effects of the inhibitor for protein kinase A or C, or tyrosine kinase (H-8, staurosporine, or genistein, respectively) on the proliferation of leukemic and normal bone marrow cells stimulated by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or interleukin-3 (IL-3) were studied using the MTT assay. These inhibitors suppressed the proliferation of leukemic and normal bone marrow cells in a dose-dependent manner. Although the suppressive effect of each inhibitor on cell proliferation was varied in each instance, the effects were almost similar whichever CSF was added. A significant difference was not recognized between leukemic and normal bone marrow cells in terms of sensitivity to these inhibitors. The data indicate that protein kinase inhibitors have an inhibitory effect on leukemic and normal hematopoietic cell proliferation and that further studies are required to determine if this effect is due to the inhibition of protein kinases acting as the second messenger of CSFs.

Cell Division↗

PubMed1990

Effects of N4-behenoyl-1-beta-D-arabinofuranosylcytosine on blast progenitors of acute myeloblastic leukemia.

To determine the antileukemic effect of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), a synthetic masked compound of 1-beta-D-arabinofuranosylcytosine, the pharmacokinetics and suppressive effect on leukemic blast progenitors of BH-AC were studied. When BH-AC was added to the suspension culture of leukemic cells, BH-AC gradually decreased in concentration in the culture media and was rapidly taken into the cellular fraction. The conversion from BH-AC to 1-beta-D-arabinofuranosylcytosine was noted in both the culture media and the cellular fraction. The concentration of 1-beta-D-arabinofuranosylcytosine converted from BH-AC in the culture medium gradually increased during 7 days of culture, although the rate of conversion was variable among the samples. BH-AC suppressed primary and secondary blast colony formation in a dose responsive manner. BH-AC also suppressed the recovery of clonogenic cells in suspension culture. The suppression by BH-AC was more prominent in secondary blast colony formation and the recovery of clonogenic cells in suspension culture than in primary blast colony formation. Secondary blast colony formation and the recovery of clonogenic cells in suspension are considered to reflect the self-renewal of blast progenitors, while primary blast colony formation is considered to reflect the terminal divisions of blast progenitors. The results obtained in the present study suggest that BH-AC is more effective to suppress the self-renewal of blast progenitors than the terminal divisions. The findings offer a theoretical basis in the utility of BH-AC in the therapy of acute myeloblastic leukemia.

Adult↗