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Biomedical subjects

Y Niho

Publications and source records attributed to Y Niho.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition by 5-fluorouracil of cis-diamminedichloroplatinum(II)-induced DNA interstrand cross-link removal in a HST-1 human squamous carcinoma cell line.

To elucidate the mechanism of the synergistic cytotoxicity of 5-fluorouracil (5-FU) and cis-diamminedichloroplatinum(II) (CDDP), we studied the interaction of these agents using a human squamous carcinoma cell line (HST-1). Exposure to 5-FU for 24 h and to CDDP for 1 h produced a 50% inhibitory concentration of 1.0 micrograms/ml (7.7 microM) and 2.5 micrograms/ml (8.3 microM), respectively. The cytotoxic action of CDDP was augmented, and a greater than additive effect was observed when the cells were exposed to 5-FU (1.0 micrograms/ml; 7.7 microM) for 24 h before the CDDP treatment. This synergistic activity was maximal when the interval between 5-FU and CDDP exceeded 24 h. In contrast, the cytotoxicity of CDDP was attenuated when it preceded the exposure to 5-FU. Thymidine did not alter the 5-FU-CDDP interaction. Evaluation of the kinetics of the removal of DNA interstrand cross-links, measured by alkaline elution, showed a significant reduction of this removal in the cells exposed to 5-FU followed by CDDP with a drug-free interval of 48 h, as compared with cells exposed to CDDP alone, or to 5-FU immediately followed by CDDP, although no differences were found in the formation of DNA interstrand cross-links by CDDP among these cells. No significant differences in the accumulation of intracellular platinum were detected by atomic absorption spectrophotometry. These findings suggest that 5-FU modulates the repair of platinum-DNA adducts, thereby potentiating the antitumor activity of CDDP.

Carcinoma, Squamous Cell↗
PubMed1992

Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs.

Hepatocyte growth factor (HGF) is a potent growth factor for various epithelial cells including mature hepatocytes and renal tubular cells. When 70% of the rat liver was excised, HGF mRNA in the intact lung markedly increased at 6 h later, then decrease to normal levels at 24 h. A similar marked increase of HGF mRNA was found in the lung of rats with hepatitis induced by CCl4. Moreover HGF mRNA in the intact lung also increased to about a 5 times higher level than the normal, within 12 h after unilateral nephrectomy. Isolated alveolar macrophages significantly expressed HGF mRNA, yet the amount remained unchanged after injury of the liver. The marked increase of HGF mRNA in lungs of partially hepatectomized rats remained even after removal of alveolar macrophages. In situ hybridization showed a marked increase of HGF mRNA signal found in endothelial cells in the lung after partial hepatectomy. We postulate that endothelial cells in the lung recognize damage of distal organs through a mediator and that lung-derived HGF may contribute to tissue repair or regeneration of injured organs, through endocrine-related mechanisms.

Animals↗
PubMed1992

Folinic acid does not mobilize hemopoietic progenitors following repeated consolidation chemotherapy for acute leukemia.

Folinic acid (FA) has been reported to expand the pool of peripheral blood stem cells (PBSC) after chemotherapy. We evaluated the efficacy of FA for harvesting PBSC following cytotoxic chemotherapy in 4 patients with acute leukemia. After achieving a complete remission (CR), 3 courses of chemotherapy for a consolidation of the CR were administered to the patients. Two successive cycles of leukapheresis were performed during the recovery phase from consolidation chemotherapy, which consisted of an intermediate dose of cytosine arabinoside. For the second cycle of leukapheresis, FA was administered intravenously at a dose of 50 mg/day following consolidation. The yields of either mononuclear cells or burst-forming units-erythroid (BFU-E) were not affected by FA administration. In contrast, the yields of colony-forming units-granulocyte/macrophage (CFU-GM) were significantly decreased in all patients compared to the CFU-GM yields after the first cycle of leukapheresis (P = 0.032). Thus FA is considered not to be effective in expanding the peripheral blood progenitor pool when given in a fashion different from the original report.

Acute Disease↗
PubMed1992

Long-term survival of human myeloid progenitor cells induced by a mouse bone marrow stromal cell line.

Mouse endothelial-adipocyte cell line (14F1.1), which induces proliferation of mouse stem cells in culture, is also capable of supporting long-term survival in culture of human myeloid progenitor cells; colony forming unit-granulocyte/macrophage (CFU-GM) was recovered from cultures incubated with the 14F1.1 cell line after over a month of incubation. The CFU-GM population increased beyond the input number, whereas, in control cultures initiated without stromal cells, the number of progenitors gradually declined. Addition of a relatively low concentration of human colony-stimulating factors (CSFs) into the cultures promoted the formation of "cobblestone areas," where mouse stroma and human hemopoietic cells closely interacted. 14F1.1 supernatant alone did not support the survival of human CFU-GM but synergized with the function of human granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate adherent macrophage proliferation.

Animals↗
PubMed1992

In vivo comparative therapeutic study of optimal administration of 5-fluorouracil and cisplatin using a newly established HST-1 human squamous-carcinoma cell line.

The efficacy and toxicity of 5-fluorouracil (5-FU) and cisplatin (CDDP) given in a sequential combination were evaluated in nude mice transplanted with HST-1, a newly established human squamous-carcinoma cell line. 5-FU and CDDP were given i.p. for 5 days and 1 day, respectively, either as single agents or in a sequential manner separated by a 24-h interval. The treatment was repeated every 30 days. Although inhibition of tumor growth was seen in all of the treated groups after two cycles, the sequence of 5-FU followed by CDDP significantly reduced the tumor burdens throughout all three courses and was more effective than the reverse sequence or either drug alone. Neither treatment-related death nor significant hematologic or nephrologic toxicities were seen, even following three cycles of therapy. Significant weight loss was observed only in mice treated with CDDP followed by 5-FU. This sequence dependence of the activity and toxicity of the 5-FU and CDDP combination should thus be incorporated into the design of a clinical trial.

Animals↗
PubMed1992

Use of a synthetic protease inhibitor for the treatment of L-asparaginase-induced acute pancreatitis complicated by disseminated intravascular coagulation.

In two patients receiving L-asparaginase therapy, severe acute pancreatitis complicated by disseminated intravascular coagulation (DIC) developed. In both cases it was successfully treated with continuous infusion of a synthetic protease inhibitor, nafamostat mesilate. In this report, we briefly discuss the clinical efficacy of the synthetic protease inhibitor in treating such cases.

Acute Disease↗
PubMed1992

Circulating CD34+ hematopoietic progenitors in the harvesting peripheral blood stem cells; enhancement by recombinant human granulocyte colony-stimulating factor.

The number of circulating progenitor cells increases during the period of hematopoietic recovery following myeloablative therapy. These progenitor cells were used for autologous transplantation in order to reconstitute hematopoiesis. As an indicator of the circulating progenitor cells, the number of granulocyte-macrophage colony forming units (CFU-GM), which is measured by means of a long-term cell culture, has been widely used. Recently, a cell surface marker, CD34, which can easily be measured by means of flowcytometry, was found to represent immature hematopoietic progenitor cells, which are very close to stem cells. Therefore, the relationship between the number of CD34 positive cells (CD34+ cells) and the number of CFU-GM in the peripheral blood following chemotherapy was studied in 9 patients selected to undergo autotransplantation. The number of peripheral blood CD34+ cells was found to be significantly correlated with that of CFU-GM (r = 0.81). When four out of 9 patients received recombinant human granulocyte-colony stimulating factor (rG-CSF) administration, a significant increase in the release of peripheral blood CD34+ cells as well as peripheral blood CFU-GM was observed (P less than 0.01). Thus, the measurement of CD34+ cells is useful for predicting the number of circulating CFU-GM.

Adolescent↗
PubMed1992

Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions.

Levels of serum granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with various leukocyte disorders were estimated by enzyme-linked immunosorbent assay (ELISA). Some cases of acute myelogenous leukemia and aplastic anemia showed elevated serum levels of G-CSF and/or GM-CSF, whereas almost all of 23 healthy controls showed G-CSF and GM-CSF levels lower than 100 pg/ml. High levels of both types of CSF were noted in patients with granulocytosis due to infection. These levels became lower after resolution of the infection. Daily changes in serum CSF levels were also examined in a patient with autoimmune neutropenia, and it was found that the peripheral neutrophilic granulocyte count changed almost in parallel with the serum G-CSF level but not with GM-CSF, following the pattern with a delay of about 4-5 h, suggesting the possibility that G-CSF mainly regulates peripheral neutrophil circulation.

Adult↗
PubMed1992

Detection of the granulocyte colony-stimulating factor receptor using biotinylated granulocyte colony-stimulating factor: presence of granulocyte colony-stimulating factor receptor on CD34-positive hematopoietic progenitor cells.

Granulocyte colony-stimulating factor (G-CSF) was linked to NHS-biotin to yield biotinylated G-CSF (b-G-CSF), which retained the ability to stimulate colony formation by normal bone marrow (BM) cells in methylcellulose. The use of streptavidin-phycoerythrin conjugate in conjunction with flow cytometry demonstrated that the binding of biotinylated G-CSF to its receptor is saturable, competitive, and specific. A 100-fold molar excess of unlabeled G-CSF almost completely inhibited the binding of the biotinylated G-CSF to the human leukemia cell line U937, which is known to possess the G-CSF receptor. G-CSF receptors were clearly detected by flow cytometry on adult human peripheral granulocytes and monocytes, but not on lymphocytes. Using this method, the expression of G-CSF receptors on hematopoietic progenitor cells in bone marrow and umbilical cord blood, detected as CD34-positive (CD34+) cells, were examined. A small but significant number of CD34+ cells were detected among the bone marrow mononuclear cells and umbilical-cord-blood mononuclear cells (4.28% +/- 0.31%, 1.09% +/- 0.20%, respectively). The percentage of CD34+ BM mononuclear cells was significantly higher than for cord blood mononuclear cells (P less than 0.01). These CD34+ cells were then analyzed by biotinylated G-CSF binding. CD34+ cells from bone marrow contained 25.8% +/- 7.9% G-CSF receptor positive cells and those from cord blood possessed 29.2% +/- 7.0% of G-CSF receptor-positive cells. The difference was not statistically significant.

Antigens, CD↗
PubMed1992

Serum granulocyte colony-stimulating factor levels in umbilical cord blood of normal full-term neonates.

We measured granulocyte colony-stimulating factor (G-CSF) levels in cord blood of 59 normal full-term neonates immediately after birth and the subsequent changes in G-CSF levels of 16 cases by our modified enzyme-linked immunosorbent assay (ELISA) for G-CSF. Ten out of 59 cases examined (17%) showed G-CSF levels in cord blood after delivery between 20 and 57 pg/ml, although in the remaining cases, the G-CSF levels were below 20 pg/ml, which was our minimal detection level. A direct relationship between G-CSF levels and white blood cell count, absolute granulocyte numbers in cord blood, gestation age or weight was not observed. Although G-CSF levels in cord blood after delivery remained below 20 pg/ml in 5 cases out of 16 tested, those in the remaining 11 cases (69%) subsequently became elevated after delivery. The peak G-CSF level in cord blood after delivery ranged from 26-364 pg/ml, and the time of it was between 4.5 and 18 h. As G-CSF level per wet weight of placenta was high (124 x 29 pg/ml), these subsequent elevations of G-CSF in cord blood after delivery may result from a gradual influx from the placenta.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Biological characteristics of CD7 positive acute myelogenous leukaemia.

We studied the biological characteristics of CD7+ acute myelogenous leukaemia (AML). We diagnosed nine out of 88 consecutive AML cases as CD7+ AML based on myeloperoxidase positivity and surface antigen expression. In eight of these nine cases more than 20% of leukaemic blasts were found to coexpress both CD7 and a myeloid-associated antigen, CD33, by a two-colour flow-cytometric assay, while in the remaining case more than 90% of blasts were positive for CD7 and myeloperoxidase. CD7+ AML was most frequently observed in M1 among AML subtypes according to the FAB classification. An early stage-specific antigen, CD34 was also expressed on leukaemic blasts from eight of these nine cases. Neither the T-cell receptor (TcR)-beta nor the TcR-gamma gene was clonally rearranged in any of the cases. We then studied the proliferative responses to stimulation by various growth factors. Among interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and granulocyte-CSF (G-CSF), IL-3 showed the strongest stimulatory effect on DNA synthesis and leukaemic blast colony formation in 8/9 and 6/8 CD7+ AML cases examined, respectively. On the other hand, the strongest stimulatory effect exerted by IL-3 on blast colony formation was observed in only six out of the 33 CD7- AML cases examined. Furthermore, CD7+ AML blasts could proliferate in response to stem cell factor (SCF); SCF alone showed stimulatory effects on blast colony formation (7/8 cases), and in 5/7 SCF-responding cases, stimulatory effects of SCF were more potent than those of IL-3. In addition, SCF enhanced blast colony formation synergistically with IL-3 in four of these seven cases. These data suggest that progenitor cells of CD7+ AML may possess the biological properties characteristic of immature haematopoietic stem cells.

Adolescent↗
PubMed1992

Interstitial 9q deletion in T-lymphoid/myeloid biphenotypic leukaemia.

We report the biological characteristics of leukaemic blasts from two cases of acute leukaemia with an interstitial deletion of the long arm of chromosome 9 (9q-). Case 1 (FAB: M1) showed del(9)(q12q22) as the sole karyotypic anomaly, and case 2 (FAB: M1) presented del(9) (q12q22) in association with trisomy 10. In both cases, leukaemic blasts presented unique cytological features, such as prominent vacuoles on Giemsa staining, or strong localization of myeloperoxidase resembling 'pseudo-Chediak-Higashi' granules. Immunophenotyping of blasts revealed the biphenotypic expression of T-lymphoid/myeloid antigens (CD2, CD7/CD33) in addition to CD34. Neither T-cell receptor beta (TCRB), T-cell receptor gamma (TCRG) nor Ig heavy chain (IGH) genes were clonally rearranged. Furthermore, there was neither rearrangement nor expression of ABL, which is located at 9q34, indicating that the deletion involved bands centrometric to 9q34 did not induce the activation of ABL. DNA synthesis of the blasts was stimulated (stimulation index greater than 2.0) in the presence of interleukin (IL)-3, IL-4, granulocyte colony-stimulating factor or erythropoietin (Epo). IL-3 and IL-4 could also support the in vitro growth of leukaemic blast colonies, and the IL-3- or IL-4-dependent blast colony growth was synergistically enhanced by the addition of IL-6 or Epo. These observations imply that T-lymphoid/myeloid or pluripotent stem cells may be closely involved in the development of 9q- AML.

Adolescent↗
PubMed1992

Purification of Pneumocystis carinii trophozoites and identification of their circulating antigens.

We have developed a new method to isolate Pneumocystis carinii trophozoites from experimental rat bronchoalveolar lavage specimens by using a Percoll discontinuous gradient and have identified the circulating antigens in experimental rat P. carinii pneumonia. The antigenic components of the trophozoites were compared with those of cysts by immunoblotting. A major immunoreactive band of 90,000 Da and some others of lower molecular mass were found in trophozoites. On the other hand, bands of 110,000, 50,000, and 45,000 Da were observed in cysts. The band of 50,000 Da was not identified when antitrophozoite rabbit serum preabsorbed with P. carinii-infected rat serum was used for immunoblotting. These results suggest that the molecule of 50,000 Da is the major circulating antigen in P. carinii-infected rats.

Animals↗