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Biomedical subjects

N Katayama

Publications and source records attributed to N Katayama.

At least 199 records · Page 11Linked to original sources
PubMed1994

Effects of lindane (gamma-BHC) and related convulsants on GABAA receptor-operated chloride channels in frog dorsal root ganglion neurons.

Effects of lindane (gamma-benzenehexachloride; gamma-BHC) on GABA-evoked Cl- current (IGABA) in freshly dissociated frog sensory (dorsal root ganglion) neurons were studied and compared with those of tert-butylbicycloortho benzoate (TBOB) and picrotoxin by the use of the suction-pipette method [13]. Drugs were applied with a rapid drug-application method, "Concentration-clamp" technique. At concentration of GABA of > 3 x 10(-6) M, at least two components of the IGABA were recognized distinct degree of desensitization. Those were defined as the peak and plateau components in the text. At low concentration (3 x 10(-7) M) of gamma-BHC, only the plateau component of IGABA at 10(-5) M were depressed without changing the peak amplitude. While gamma-BHC at high concentration (3 x 10(-5) M) depressed both the peak and plateau current components. The gamma-BHC-induced depression of IGABA seemed to be IGABA-component-dependent. A detailed analysis of the gamma-BHC action in the concentration-response relationship for GABA revealed that the IGABA with strong desensitization was preferentially blocked by gamma-BHC (3 x 10(-5) M). The rate of recovery of the IGABA from gamma-BHC-induced block depended on the concentration of GABA. The lower the concentration of GABA, the slower the recovery. The GABAA receptor Cl- channels were proposed to be classified into two types of the gamma-BHC-sensitive and -resistant ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Myricetin and quercetin, the flavonoid constituents of Ginkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca(2+)-loaded brain neurons.

The antioxidant action of myricetin and quercetin, the flavonoid constituents of the extract of Ginkgo biloba (EGb), on oxidative metabolism of brain neurons dissociated from the rats was examined using 2',7'-dichlorofluorescin (DCFH) which is retained within the neuron and then is oxidized by cellular hydrogen peroxide to be highly fluorescent. Incubation with myricetin or quercetin reduced the oxidation of DCFH in resting brain neurons, more profoundly than EGb. Myricetin decreased the oxidative metabolism at concentrations of 3 nM or more. It was 10 nM or more for the case of quercetin. Incubation with each flavonoid constituent also reduced the Ca(2+)-induced increase in the oxidative metabolism without affecting the cellular content of DCFH or the intracellular concentrations of Ca2+. Such an antioxidant action of myricetin or quercetin may be responsible for a part of the beneficial effects of EGb on brain neurons subject to ischemia.

Animals↗
PubMed1994

Synergistic interaction between interleukin-12 and steel factor in support of proliferation of murine lymphohematopoietic progenitors in culture.

We have investigated the effects of interleukin (IL)-12 (natural killer cell stimulatory factor/cytotoxic lymphocyte maturation factor) on the proliferation of murine myeloid and lymphohematopoietic progenitors in methylcellulose culture. In the presence of erythropoietin (Ep), IL-12 alone failed to support colony formation by mononuclear and enriched marrow cells of normal mice. Steel factor (SF) alone supported primarily formation of granulocyte/macrophage (GM) colony formation. However, the combination of the two cytokines yielded a significant number of multilineage colonies. When tested on marrow cells from 5-fluorouracil (5-FU)-treated mice, the combination of IL-12 and SF, but not the single factors, was effective in support of formation of various types of colonies. Approximately 25% of these colonies yielded pre-B-cell colonies when replated in secondary culture containing SF and IL-7, indicating that IL-12 can interact with SF in supporting the development of primitive lymphohematopoietic progenitors. These results demonstrate that IL-12, a cytokine believed to be involved in the development of cell-mediated immune responses, has a wider range of activity, including committed myeloid and multipotent lymphohematopoietic progenitors.

Animals↗
PubMed1994

Enrichment for primitive hemopoietic progenitors of marrow cells from 5-fluorouracil-treated mice and normal mice.

Study of the mechanisms regulating stem cells would be significantly facilitated if a purified population of stem cells were available. During the last 4 years, our laboratory has been engaged in enrichment of murine marrow cells for primitive hemopoietic progenitors. We primarily used marrow cells from mice treated with 150 mg/kg of 5-fluorouracil (5-FU), and our assay for the primitive progenitors was formation of multilineage colonies supported by a combination of interleukin-3 (IL-3) and IL-6. First, we found that post-5-FU marrow cells with a density of 1.0631-1.0770 g/cm3, negative for lineage-specific markers and positive for Ly-6A/E are routinely enriched for multipotential progenitors by approximately 800-fold. We then observed that J11d.2 and c-kit are additional useful markers for further enrichment of the primitive hemopoietic progenitors. Cell cycle-dormant primitive progenitors are primarily in the J11d.2+ fraction, whereas more mature progenitors are J11d.2-. The primitive progenitors express relatively low levels of c-kit, while more mature, actively cycling progenitors express high levels of c-kit. Combinations of these markers may be useful in enrichment of marrow cells of normal mice for primitive hemopoietic progenitors.

Animals↗
PubMed1994

[Auer-rod-like bodies in plasma cells in patient with plasma cell dyscrasia].

Auer-rod-like bodies were found in plasma cells from a 74-year-old man with plasma cell dyscrasia. These bodies exhibited red purple staining by May-Giemsa staining and were indistinguishable from Auer bodies often found in acute myeloid leukemia. These bodies, however, failed to stain with peroxidase and showed acid phosphatase positivity. Bone marrow examinations were performed three times at the sternum or iliac crest. The proportions of plasma cells were 4.4%, 3.4% and 3.8%. The Auer-rod-like bodies were found in 0.05% (2/3824), 0.07% (4/6883) and 0.08% (2/2656) of the plasma cells.

Aged↗
PubMed1993

Stage-specific expression of c-kit protein by murine hematopoietic progenitors.

We have analyzed c-kit expression by hematopoietic progenitors from normal and 5-fluorouracil (5-FU)-treated mice by staining with monoclonal anti-c-kit antibody ACK-4. Marrow cells that were enriched for progenitors by a combination of metrizamide density separation and negative immunomagnetic selection with lineage-specific monoclonal antibodies (MoAbs) were separated into three populations based on the level of c-kit expression, c-kit(high), c-kit(low), and c-kit-. The majority of colony-forming cells from normal mice were in c-kit(high) population, whereas most of the progenitors from 5-FU-treated mice were in the c-kit(low) population. Optimal colony formation from c-kit(low) cells from 5-FU-treated mice required the interactions of at least two factors among interleukin-3 (IL-3), IL-11 and steel factor (SF) whereas colony formation from c-kit(high) cells of normal mice was supported well by IL-3 alone. Blast cells that were derived from 5-day culture of c-kit(low) post 5-FU cells were c-kit(high). These observations suggest that the primitive hematopoietic progenitors in cell cycle dormancy are c-kit(low) whereas actively cell cycling maturer progenitors are c-kit(high). Mature cells, with the exception of mast cells, derived from secondary culture of the c-kit(high) blast cells expressed little, if any, c-kit. These results are consistent with a model in which c-kit expression progresses from low levels on primitive, dormant multipotent progenitors to high levels on later, actively cycling progenitors, and finally, decreases to very low or undetectable levels on most mature blood cells, with the exception of mast cells.

Animals↗
PubMed1993

Biologic characteristics of acute leukemia after myelodysplastic syndrome.

Ten patients with acute leukemia after primary myelodysplastic syndrome (MDS-AL) were examined to clarify the biologic nature of the leukemic cells in comparison with that of de novo acute myelocytic leukemia (AML). The morphologic and cytochemical features of the leukemic cells from all these patients corresponded well to those of de novo AML, and they were diagnosed with MDS-AML. Phenotypically, the frequent expression of the lymphocyte activation antigens, CD25 and CD30, was characteristic in MDS-AML. The in vitro response of MDS-AML cells to various growth factors was similar to that of de novo AML cells. Transforming growth factor beta 1 (TGF beta 1) suppressed growth factor-dependent colony formation by normal bone marrow cells, MDS bone marrow cells, and de novo AML cells, but did not inhibit colony formation by MDS-AML cells. The number of TGF beta 1 high-affinity binding sites of MDS-AML samples (< 5 to 47 sites/cell) was markedly lower than that in de novo AML samples (120 to 221 sites/cell). Our results indicate that the reduced TGF beta 1 may represent disregulation of the proliferation system in MDS-AML cells. This is thought to occur during the MDS phase, and may be related to the poorer response shown to conventional chemotherapy of AML.

Adult↗
PubMed1993

Growth factor requirement for survival in cell-cycle dormancy of primitive murine lymphohematopoietic progenitors.

We used enriched marrow cells from mice administered three doses of 150 mg/kg 5-fluorouracil (5-FU) 1, 3 and 7 days before they were killed to study the effects of different growth factors on the survival of primitive, cell-cycle dormant progenitors in culture. This cell population yielded substantially fewer colonies in response to single growth factors than corresponding preparations from day 2 post-5-FU bone marrow samples, and the majority of progenitors were multipotential in nature. These observations were consistent with the prediction that multiple cycles of 5-FU treatment would further enrich for primitive cells. With this cell population, we found that among all the factors tested, interleukin-3 (IL-3) and steel factor (SF) as single factors are the most effective in supporting survival of dormant primitive progenitors. Interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), interleukin-11 (IL-11), interleukin-4 (IL-4), interleukin-1 alpha (IL-1 alpha), and tumor necrosis factor-alpha (TNF-alpha) also supported survival of a few progenitors, but much less effectively than either IL-3 or SF. The hematopoietic progenitors that survived for 1 week in liquid culture supplemented with either IL-3 or SF retained the capability to develop pre-B-cell colonies in secondary culture. Our results demonstrate that survival of dormant murine lymphohematopoietic cells in culture is dependent on the presence of specific growth factors, and that this growth factor requirement can be satisfied well by SF or IL-3.

Animals↗
PubMed1993

Distribution characteristics of immunosuppressants FK506 and cyclosporin A in the blood compartment.

Using two representative immunosuppressants, FK506 (FK) and cyclosporin A (CyA), of which the mechanism of pharmacological action is the same although there is a great difference in the pharmacological intensity, the distribution characteristics were studied in both in vivo and in vitro experiments using rat, dog, and human blood. Blood samples were fractionated by means of sedimentation in Ficoll-Paque, and the drug contents in the diluted plasma fraction, erythrocyte fraction, and lymphocyte fraction were measured by an HPLC method. FK distributes to the lymphocyte fraction to a level about three times greater than that of CyA, while CyA distributes to the erythrocyte fraction to a level ten times that of FK. The distribution pattern of these fractions was independent of the drug concentration and species after correcting the drug concentration in each fraction with the blood drug concentration. The uptakes of FK and CyA in the isolated lymphocytes obtained from the rat spleen and human peripheral blood were also studied. The amount of FK taken up by the spleen lymphocytes is five times greater than that of CyA. In the case of the uptake study using human peripheral blood lymphocytes, the concentration of FK in the lymphocyte is 100-fold higher than that of CyA. This difference in the lymphocyte level between the two immunosuppressants is thought to be one of the reasons why FK is more potent than CyA, a difference of about 100-fold in the in vitro pharmacological study and about tenfold in the in vivo organ transplantation experiments.

Animals↗