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Biomedical subjects

A Horikoshi

Publications and source records attributed to A Horikoshi.

At least 55 records · Page 3Linked to original sources
PubMed1986

Relapsing process in FAB subtypes of adult acute leukemia and its relationship to treatment regimens.

The relapsing process in the bone marrow was studied in those 77 patients with adult acute leukemia, diagnosed according to the FAB classification who achieved complete remission (CR) and then received intermittent multi-drug intensification treatment. Relapse occurred in most of the patients who exhibited Auer rods or Ph1 chromosomes in the bone marrow, or in whom blasts increased to 8% or more, but some patients remained in CR by subsequent treatment, that is, relapsing process was reversible. With our conventional treatment, the relapse or relapsing process occurred in most of the patients with L1, L2 and M1 subtypes within 6 months and was irreversible. It occurred mainly between 5 and 13 months in those with M2, M3 and M5 and was reversible in some cases. Patients with M4 subtype received intensified treatment due to the difficulty of achieving remission; relapse was seen in only 3 of 7 cases. To prevent relapse and attain a potential cure, the treatment should be intensive before the relapsing process with adequate supporting care. In view of the above-mentioned observations, our new treatment protocols for acute leukemia were designed to be more intensive than those conventionally employed, and to be discontinued within approximately 10 months in lymphoblastic leukemia and approximately 8 months in myeloid leukemia.

Adult↗
PubMed1985

Effect of hydrocortisone and BCNU on long-term murine bone marrow cultures.

Hydrocortisone (HC) has been observed to influence an in vitro Dexter culture system with maintenance of pluripotent hematopoietic stem cells (CFU-s) and progenitor cells (CFU-gm, BFU-e). In the present study, a two-phase murine Dexter culture system was established to study the mechanism of HC-mediated suppression of stem cells or progenitor cells. Furthermore, the effect of exposing 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to an adherent cell layer for 1 h was investigated for maintenance of progenitor cells. Cultures supplemented with selenium and transferrin showed relatively good growth. The BFU-e number was significantly enhanced at 2 and 3 weeks of culture in the BCNU-treated group. This system is a good model for monitoring the influence of agents to a hematopoietic-inductive microenvironment.

Animals↗
PubMed1984

Characterization of human bone marrow long-term cultures.

In an attempt to more closely simulate the native hematopoietic environment, human bone marrow bony matrix was cultivated in long-term human bone marrow cultures. Sternal bone marrow curettings (i.e., 'bony matrix') were cultured with and without autologous bone marrow single cell suspensions. Fresh media were provided at weekly intervals and the 'harvested' cells were assayed for CFU-gm (i.e., the granulocyte-macrophage precursor). Bone marrow bony matrix alone was not competent to maintain CFU-gm production, although early in the culture nucleated cells and CFU-gm were recruited from the bony matrix. A dose of 850 rad of X-radiation to the bone marrow matrix damaged the hematopoietic growth-promoting effects of the adherent cell layer, which was, however, rapidly reconstituted by an inoculation of intact autologous bone marrow cells. Additional investigations revealed that, whereas the addition of hydrocortisone to this culture system did not alter the maintenance of CFU-gm, recharging the cultures with fresh autologous marrow maintained CFU-gm for 10 weeks. These data indicate that human bone marrow stroma is more sensitive to X-irradiation in vitro than in vivo, and the bone marrow hematopoietic microenvironment provided by its bony matrix seemed to be less effective in vitro than in vivo with respect to the maintenance of hematopoietic precursor cells.

Adult↗
PubMed1983

Colony-stimulating activity in murine mixed leukocyte cultures.

Mixed leukocyte cultures (MLC) were prepared utilizing mouse spleen cells from strains with: (1) major histocompatibility complex (MHC) differences, (2) many non-MHC gene differences, and (3) only a few non-MHC gene differences. After 4 days, the conditioned media (CM) of MLC from (1) and (2) above were found to contain high granulocyte/macrophage colony-stimulating activity (CSA) when assayed in methylcellulose clonal cultures. Also the stimulation index (SI) of CSA was elevated on day 4 of incubation, even though 3H-Thymidine (3HTdR) incorporation and SI as measured by 3HTdR increased at 4 and 6 days, respectively. However, MLC-CM from mouse strains with only a few non-MHC gene differences contained low titers of CSA after 4 days in culture, and this was paralleled by a low SI. For MLC with MHC differences, and with many non-MHC gene differences, the response detected by an increase in CSA production appeared more promptly and was perhaps more sensitive when compared with 3HTdR incorporation in the mixed leukocyte reaction (MLR). From these results, we conclude that the presence of CSA in MLC-CM at 4 days of culture represents a good marker for the degree of MLR, and we postulate that the CSA titer in MLC-CM may be relevant for the prediction of graft-versus-host reactions (GvHR).

Animals↗
PubMed1983

In vivo stimulation of murine granulopoiesis by human urinary extract from patients with aplastic anemia.

Significant in vivo stimulation of granulopoiesis was induced in mice by the administration of an extract from the urine of patients with aplastic anemia (AA). Sialic acid has been identified as an important molecular component for the in vivo biological activity of this granulopoietic factor, "granulopoietin," which is distinct and different from endotoxin. Urine from patients with AA was successively fractionated by Sephadex G-50 and DEAE-cellulose chromatography. The resultant extract, which we refer to as AA urinary extract, contained approximately equal to 44 international units of erythropoietin per A unit of protein and induced 15,000 colonies of granulocyte/macrophage precursor cells (granulocyte/macrophage colony-forming units, CFU-gm) per A unit of protein with mouse bone marrow. Eight daily intraperitoneal injections of this extract in mice induced a 6.2-fold increase in peripheral blood granulocytes and a 14.6-fold increase of splenic CFU-gm, with concomitant increases in the proliferation rates of CFU-gm in both bone marrow and spleen. Pretreatment of the AA urinary extract with sialidase significantly diminished these granulopoietic effects in vivo (P less than 0.001). In contrast, both extracts (i.e., native AA and sialidase-treated AA urinary extracts) revealed high granulocyte/macrophage colony-stimulating factor activity in vitro when clonal assays were performed with mouse bone marrow. Increased in vivo and in vitro granulopoietic activities were found in the concanavalin A "break-through" fraction, indicating that these activities were due to protein(s) that did not bind to the lectin. These results reveal that this urinary extract from patients with AA is capable of inducing significant granulopoiesis in mice and that sialic acid is an important component in the maintenance of this granulopoietic effect in vivo but not in vitro.

Anemia, Aplastic↗
PubMed1983

Comparative effects of chlorozotocin and BCNU on hematopoietic precursor cells.

Comparative studies to determine the suppressive effects of chlorozotocin (2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose) and BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) on mouse and human hematopoietic precursor cells: granulocyte-macrophage precursor cells (CFU-gm), late erythroid precursor cells (CFU-e), and early erythroid precursor cells (BFU-e) were performed after in vitro incubation of 1 h with drug concentrations based on clinical administration levels. The suppressive effect of chlorozotocin on CFU-gm, BFU-e, and CFU-e hematopoietic precursor cells in the mouse was less than that of BCNU with the most significant difference seen in CFU-e colony formation. For human hematopoietic progenitor cells, however, the suppressive effect of chlorozotocin was far less than that of BCNU. When the effects of 40 micrograms/ml of chlorozotocin and 20 micrograms/ml of BCNU on human marrow were compared, there were statistically significant differences found for CFU-gm colony formation, and BFU-e and CFU-e colony numbers were significantly different for the two drugs at all comparable concentrations tested. Our results confirm the clinical data, and establish that the effects of chlorozotocin on human hematopoietic precursor cells are minimal.

Animals↗
PubMed1982

Comparative effects of chemotherapeutic drugs on human and murine hematopoietic progenitors in vitro.

Using semi-solid clonal assay systems, the cytocidal effects of chemotherapeutic drugs on hematopoietic progenitors (CFU-gm, BFU-e, CFU-e) were compared with their effects on K-562 human leukemia cells. The chemotherapeutic drugs used for these experiments were daunorubicin, cytosine arabinoside, vincristine, methotrexate, bis-chlorethyl-nitrosourea and chlorozotocin. After the cells were exposed for either 1 or 24 h to several concentrations of each drug, clear differences in suppressive effects were seen. The experimental applications of this technology and the clinical implication of these results are discussed.

Animals↗
PubMed1982

Colony stimulating factor in human mixed leukocyte cultures.

Colony stimulating factor (CSF) is important for granulocyte/macrophage proliferation and differentiation. We investigated the relationship between the immune reactivity and the production of CSF by using two-way mixed leukocyte cultures (MLC) prepared from human peripheral mononuclear cells obtained with the aid of a blood cell separator. Assessed over 9 days of MLC incubation, the level of CSF in the supernatant reached a maximum at day 7 and then decreased. Optimal number of MLC cells ranged from 1 X 10(6)/ml to 2 X 10(6)/ml; CSF activity decreased at a cell concentration of 4 X 10(6)/ml. There was a differential sensitivity between cluster formation and colony formation to MLC-CSF. MLC-CSF is not species specific and hence, can stimulate both human and mouse CFU-c. MLC-conditioned medium (MLC-CM) appears to be a potentially useful source of CSF.

Animals↗
PubMed1980

Humoral immunologic responses in idiopathic juvenile periodontitis (periodontosis).

Humoral responses were examined in idiopathic juvenile periodontitis (IJP) including antibody titers to representative strains of the five groups of periodontosis-associated bacteria. Titers as determined by indirect immunofluorescence were compared in IJP, non-IJP family members, periodontitis and periodontally healthy subjects. Serum concentrations of IgG, IgA, IgM and IgE were also assayed. Antibody titers to the periodontosis-associated bacteria were generally low. Some disease specificity was observed in that titers to Groups II and III bacteria were highest in IJP. These titers in IJP were significantly higher (P less than 0.01) than in the other subjects. Titers to Group I bacteria were similar in all periodontal groups except the periodontally healthy subjects where titers were the lowest. Titers to Group I bacteria were significantly higher (P less than 0.01) than in the periodontally healthy subjects. Titers to Groups IV and V were uniformly low in all periodontal groups. Immunoglobulin concentrations of IgA, IgM and IGE were similar in IJP and non-IJP. The IgG concentrations in IJP, while within the normal range were significantly higher in IJP compared to non-IJP family members.

Adolescent↗
PubMed1979

Simplified technique for sonication and processing of dental plaque samples.

A simplified method for processing dental plaque samples was devised and compared to previously used methods. Analysis of 36 nonstandardized subgingival plaque samples from various states of periodontal health and disease and 12 standardized supragingival plaque samples demonstrated that there was no significant difference between the recovery offered by the two techniques. Comparable recovery, increased convenience, and adaptation to the clinical setting suggests that implementation of this simplified technique may be of great value.

Aged↗