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Biomedical subjects

Y Honma

Publications and source records attributed to Y Honma.

At least 217 records · Page 12Linked to original sources

Interleukin-4 inhibits the differentiation of mouse myeloid leukemia M1 cells induced by dexamethasone, D-factor/leukemia inhibitory factor and interleukin-6, but not by 1 alpha,25-dihydroxyvitamin D3.

The effects of interleukin-4(IL-4) on the growth and differentiation of mouse myeloid leukemia M1 cells induced by various differentiation inducers were investigated. IL-4 alone did not have any significant effect on the growth or differentiation of M1 cells, but inhibited their differentiation induced by dexamethasone, D-factor/leukemia inhibitory factor, or interleukin 6. IL-4 also restored the proliferation of M1 cells after growth inhibition during their induction of differentiation by inducers. In contrast, IL-4 enhanced inhibition of growth and induction of differentiation of M1 cells by 1 alpha,25-dihydroxyvitamin D3. These results indicate that modulation of differentiation of M1 cells by IL-4 depends on the differentiation inducer.

Animals↗

Induction by some protein kinase inhibitors of differentiation of a mouse megakaryoblastic cell line established by coinfection with Abelson murine leukemia virus and recombinant SV40 retrovirus.

Mouse C1 line cells are megakaryoblastic cells established by coinfection of Abelson murine leukemia virus and recombinant simian virus 40. We examined the effects of various compounds on growth and differentiation of these cells. Megakaryocytic differentiation of C1 cells was not induced by cytokines that stimulate megakaryocytic maturation of normal progenitor cells, such as interleukin 3 and 6 and granulocyte-macrophage colony-stimulating factor. However, the cells were induced to differentiate into megakaryocytes by treatment with some protein kinase inhibitors. The inhibition of v-abl tyrosine kinase activity preceded induction of differentiation of the cells treated with tyrosine kinase inhibitors such as genistein, herbimycin A, and erbstatin. Treatment of C1 cells with a v-abl antisense oligomer inhibited their proliferation and induced acetylcholinesterase activity, a typical marker of megakaryocytic differentiation. These results suggest that inhibition of v-abl function is associated with induction of megakaryocytic differentiation of C1 cells. Among the compounds tested, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of cyclic nucleotide-dependent and Ca(2+)-phospholipid-dependent (protein kinase C) protein kinases, was the most potent inducer of differentiation of C1 cells. However, the differentiation-inducing effect of H-7 was unlikely to be mediated through inhibition of protein kinase C or cyclic nucleotide-dependent kinases, because other types of inhibitors of these kinases were not effective, and a protein kinase activator (phorbol ester) induced differentiation of C1 cells. Moreover, neither v-abl mRNA expression nor v-abl kinase activity in C1 cells was affected by treatment with H-7. These findings indicate that induction of megakaryocytic differentiation by H-7 is not related to inhibition of v-abl kinase, but rather to some novel function of H-7.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Hemin enhances the sensitivity of erythroleukemia cells to 1-beta-D-arabinofuranosylcytosine by both activation of deoxycytidine kinase and reduction of cytidine deaminase activity.

The sensitivity of human myelogenous leukemia cells to 1-beta-D-arabinofuranosylcytosine (ara-C) during induction of differentiation was examined. Treatment with hemin greatly increased the sensitivity of erythroid leukemia cells to ara-C. The enhancement of ara-C sensitivity by hemin was not as remarkable in nonerythroid leukemia cells. Hemin altered the metabolism of ara-C in human erythroleukemia K562 cells by reducing ara-C deaminase activity, increasing intracellular accumulation of ara-C, and activating the nucleoside kinases. These alterations may be involved in the enhancing effect of hemin on sensitivity of ara-C. These results suggest that some inducers of differentiation potentiate the antileukemic effect of ara-C on human erythroleukemia cells.

Cell Differentiation↗

Induction of differentiation of human myeloid leukemia HL-60 cells by novel pyrimidine nucleoside analogs.

New pyrimidine nucleoside analogs (18 compounds) were synthesized and their growth-inhibiting and differentiation-inducing activities on human myeloid leukemia HL-60 cells were examined. Some of the analogs were found to induce nitroblue tetrazolium (NBT) reducing activity in the HL-60 cells. The inducing activities of these compounds were compared at their concentrations for 50% inhibition of cell growth. TI-79 (3-benzyl-5-methyl-3-(beta-D-ribofuranosyl)pyrido[2,3-d]pyrimidine- 2,4(1H,3H)-dione) was a very effective inducer of NBT-reduction and of differentiation of the cells into mature granulocytes. The induction of NBT-reducing activity by TI-79 was inhibited by high concentrations of the natural nucleoside, adenosine. Other differentiation inducers, such as retinoic acid, 1 alpha,25-dihydroxyvitamin D-3 and staurosporin markedly enhanced the induction of differentiation of HL-60 cells by TI-79. Nucleoside analogs such as TI-79 should be useful for differentiation therapy of some types of myelogenous leukemia.

Adenosine↗

Induction of differentiation of human leukemia cells by inhibitors of myosin light chain kinase.

Inhibitors of myosin light chain kinase, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) and 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7), induced Nitroblue tetrazolium reducing activity, lysozyme activity and morphological maturation of human monoblastic U937, THP-1 and promyelocytic HL-60 cells, but not of erythroblastic K562 cells. However, three analogs of ML-9, which are an inhibitor and an activator of protein kinase C, and a calmodulin antagonist, respectively, did not induce differentiation of the cells.

Azepines↗

Inhibition by erythroid differentiation factor (activin A) of P-glycoprotein expression in multidrug-resistant human K562 erythroleukemia cells.

The K562/VCR cell line, exhibiting acquired multidrug resistance (MDR) with increased expression of a cell surface glycoprotein (P-glycoprotein), was isolated from human erythroleukemia K562 cells. Various compounds that induced erythroid differentiation of K562 cells were tested for their effects on growth and differentiation of these K562/VCR cells. Sodium butyrate, hemin, 1-beta-D-arabinofuranosylcytosine, and erythroid differentiation factor (EDF) induced erythroid differentiation of K562/VCR cells as well as K562 cells. The MDR of K562/VCR cells was partly overcome by treatment with EDF but not with the other inducers. Expression of P-glycoprotein by K562/VCR cells was measured by radioimmunoassay using MRK16 monoclonal antibody. Results showed that EDF caused down-regulation of P-glycoprotein in K562/VCR cells, whereas the other inducers did not cause its down-regulation. Thus, in addition to inducing erythroid differentiation, EDF enhanced the sensitivity of K562/VCR cells to multidrugs and suppressed expression of P-glycoprotein. These results suggest that differentiation inducers may be useful in chemotherapy of leukemic MDR cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Exocytotic release of neurotransmitters from nerve fibers in the endocrine pancreas (Brockmann body) of the teleost, Takifugu niphobles.

Exocytotic release of neurotransmitters was ultrastructurally investigated in the endocrine pancreas (Brockmann body) of the teleost, Takifugu niphobles. Exocytotic figures of large cored vesicles were found not only on the surface of nerve fibers facing the endocrine cells directly, but also on their surface facing the space of connective tissues including the blood capillaries. The results indicate that some 'neurotransmitters' are released non-synaptically in the endocrine pancreas and that some 'neurotransmitters' may enter the blood stream as 'neurosecretory hormones.'

Animals↗

Immunocytochemical distribution of FMRFamide-like substance in the brain of the cloudy dogfish, Scyliorhinus torazame.

The distribution of the molluscan cardioexcitatory tetrapeptide FMRFamide (Phe-Met-Arg-Phe-NH2) in the brain of the cloudy dogfish, Scyliorhinus torazame, was examined by immunocytochemistry. FMRFamide-like immunoreactivity was demonstrated to occur extensively in various regions of the dogfish brain, except for the corpus cerebelli. Immunoreactive neuronal perikarya were located in the ganglion of the nervus terminalis, the preoptic area, and the hypothalamic periventricular gray matter consisting of the nucleus medius hypothalamicus, the nucleus lateralis tuberis, and the nucleus lobi lateralis. Some of the immunoreactive cells in the hypothalamus were identified as cerebrospinal fluid-contacting neurons. The bulk of the immunostained fibers in the nervus terminalis penetrated into the midventral portion of the telencephalon and ran dorsocaudally toward the basal telencephalon and hypothalamus, showing radial projections or ramifications. The labeled fibers were abundant in the midbasal part of the telencephalon and in the hypothalamus, where some fibers were found in loose networks around the cell bodies of the nucleus septi and hypothalamic periventricular nuclei. The fibers demonstrated in the hypothalamus terminated around the vascular wall of the primary capillary plexus of the median eminence or penetrated deeply into the pars intermedia of the hypophysis. These results suggest that, in the dogfish, an FMRFamide-like substance participates in the regulation of adenohypophysial function. This molecule may have a role as a neurotransmitter and/or neuromodulator in the central nervous system.

Amino Acid Sequence↗

Induction of differentiation of human myeloid leukemia HL-60 cells by novel nonphosphorus alkyl ether lipids.

We synthesized a new series of nonphosphorus alkyl ether glycerolipids, in which the 2-acetyl group of platelet-activating factor was replaced by a pyrimidin-2-yl group and the 3-phosphocholine portion by an omega-(substituted ammonio)ethoxyethyl side-chain including omega-thiazolio-, imidazolio- and pyridinio groups with or without a carboxyl substituent, respectively (compound I-XI). Their effects on cell proliferation and differentiation of human myeloid leukemia HL-60 cells were examined. Incubation of HL-60 cells with these cationic and zwitterionic alkyl ether lipids inhibited proliferation of HL-60 cells with IC50 values ranging from 10 to 500 ng/mL. The cells were induced by the lipids to differentiate into morphologically and functionally mature granulocytes. Among the compounds we tested, 1-octadecyl-2-pyrimidinyl-3-[3-(5- carboxylatepentyl)imidazolioethoxyethyl]glycerol (compound I) was the most effective in inducing differentiation of HL-60 cells. Compound I showed on a molar basis, an inhibitory effect on the leukemic cells over 50 times greater than did 2-(2-dodecyloxyethoxy)ethyl 2-pyridinio-ethyl phosphate, the antileukemic alkyl ether phospholipid.

Antineoplastic Agents↗

Effects of inhibitors of protein tyrosine kinase activity and/or phosphatidylinositol turnover on differentiation of some human myelomonocytic leukemia cells.

The activities of protein tyrosine kinase and phosphatidylinositol turnover have been found to be associated with cell growth and differentiation. We examined the effects of some inhibitors for these biochemical activities in human myelogenous leukemia cells. Genistein, which is known to inhibit the activities of protein tyrosine kinase, phosphatidylinositol turnover and topoisomerase II, induced nitroblue tetrazolium (NBT) reduction and lysozyme activity in ML-1, HL-60 and U937 cells. Morphological studies showed that genistein-induced differentiation of myeloblastic ML-1 cells into promyelocytes and of promyelocytic HL-60 cells into mature granulocytes. The differentiation-inducing effect of genistein was augmented by addition of 1 alpha,25-dihydroxyvitamin D3 (VD3) or retinoic acid, VD3 being more effective than retinoic acid. Methyl 2,5-dihydroxycinamate, a protein tyrosine kinase inhibitor, had only a weak effect in inducing differentiation of ML-1 cells. On the other hand, psi-tectorigenin was more effective than genistein in inducing the differentiations of ML-1 and HL-60 cells. Psi-tectorigenin is reported to inhibit phosphatidylinositol turnover without inhibiting protein tyrosine kinase. Thus modulation of phosphatidylinositol turnover might be more important than that of protein tyrosine kinase activity for differentiation of some myelogenous leukemia cells.

Cell Differentiation↗

Inhibition by vitamin D3 of erythroid differentiation of human leukemia line cells induced by transforming growth factor beta or erythroid differentiation factor (activin A).

Erythroid differentiation of human leukemic cell lines (HEL, KU812F and K562) was induced by their treatment with transforming growth factor beta (TGF-beta) or erythroid differentiation factor (EDF/Activin A). Their erythroid differentiation was markedly inhibited by vitamin D3, dexamethasone or 12-O-tetradecanoyl-phorbol-13-acetate, which are known to induce monocytic differentiation of leukemic cells. These results suggest that inducers of monocytic differentiation may switch off cellular regulatory mechanisms for induction by TGF-beta and EDF of erythroid differentiation of leukemia cells.

Activins↗

Monitoring of cortical blood flow during temporary arterial occlusion in aneurysm surgery by the thermal diffusion method.

During aneurysm surgery, regional cortical blood flow (CoBF) was continuously monitored in 12 patients with a thermal diffusion flow probe in an attempt to assess the effects of temporary major arterial occlusion on blood flow and outcome. When the CoBF was above 30 ml/100 g/min, the safe period for temporary clipping applied distal to the perforators was 15 minutes. The occlusion time should be shortened when the CoBF is below 30 ml/100 g/min. Two patients suffered basal infarction, which was not detected by CoBF monitoring. Attention should be paid to the blood flow in the deep structures when a temporary clip is applied at a site proximal to the perforating branches. Direct measurement of CoBF may be of value in estimating the time that temporary occlusion of a major vessel can be tolerated.

Aged↗

Exposure of the intracavernous carotid artery in aneurysm surgery.

The pterional intradural approach was used in five cases of large and giant carotid-ophthalmic aneurysms and in two cases of intracavernous aneurysms that arose from the anterior siphon knee in the cavernous sinus (CS) and extended into the carotid cistern. In four cases of large carotid-ophthalmic aneurysms removal of the anterior clinoid process and the roof of the optic canal gave easy access to the pericarotid ring. The anteromedial part of the pericarotid ring was dissected to expose the extradural portion of the internal carotid artery (ICA) proximal to the neck and to make enough room between the wall of the CS and the extradural portion of the ICA, thus allowing easy clipping of the neck. In one case of a giant carotid-ophthalmic aneurysm extending into the CS with an extradural origin of the ophthalmic artery and in two cases of an intracavernous aneurysm arising from the siphon knee, neck clipping was performed by opening the lateral wall and roof of the CS after removal of the optic strut. The opening of the lateral wall anterior to the 3rd nerve facilitated wide exposure of the anterior siphon knee. The horizontal portion of the intracavernous ICA as well as the whole aspect of the aneurysm could be exposed as a result of the extended opening of the cavernous roof anterior to the posterior clinoid process. Successful operative results were obtained in all seven patients. A visual field detect as an operative complication was noted in one patient. No disturbance of ocular movements was noted.

Adult↗

Assessment of 99Tcm-HMPAO tumour scintigraphy using VX-2 tumours implanted in a lower limb muscle of rabbits.

Tumour scintigraphy using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) was investigated in VX-2 tumours implanted in the muscles of the lower legs of rabbits to assess the feasibility of using this agent clinically for this procedure. On the time-activity curves for 99Tcm-HMPAO in the tumour, an initial peak and a subsequent decrease of radioactivity immediately after the initial peak were observed, while there was a slow, gradual decrease of activity over the next hour. The tumour/normal muscle ratio of HMPAO activity during this period was high and constant, and was independent of time. Comparison of the static images of 99Tcm-HMPAO with angiography and histological findings suggests that the tumour image of 99Tcm-HMPAO reflects tumour blood perfusion. These findings indicate that the distribution of 99Tcm-HMPAO on static images can provide a qualitative assessment of the perfusion of the tumour, despite the limitations of this tracer for quantifying tumour blood flow due to its early efflux from the tumour.

Animals↗

[Influence of low level antibiotics on Pseudomonas aeruginosa].

Erythromycine (EM) and chrolamphenicol (CP), the inhibitors of protein synthesis, were quantitatively examined for the growth of Pseudomonas aeruginosa EA83 and its production of extracellular proteins. The minimal inhibitory concentration (MIC) of EM for the strain was higher than 100 micrograms/ml and that of CP was 100 micrograms/ml. The growth curve of EA83 was not influenced by adding 5 micrograms/ml of EM to the broth culture, but proteolytic activity and the total protein in the culture supernate went down to 60% of the control. Number of organisms in 20 hour culture was almost constant regardless of EM concentration ranging from 0 to 50 micrograms/ml, however, the suppression of proteolytic activity and total protein in the culture supernate was seen even at 1 micrograms/ml of EM concentration. The degree of suppression was inversely proportional to EM concentration. This phenomenon was also seen in the substitution of CP for EM. All extracellular proteins separated on SDS-PAGE decreased the amount as increasing EM in the culture media. These results suggested that EM inhibited the production of not only protease including elastase, but also any other extracellular proteins including well known pathogenic factors such as exotoxin A and phospholipase C.

Chloramphenicol↗

[Histological grading of alveolar type renal cell carcinoma based on architectural variation].

Ninety-two of a total 107 renal cell carcinomas excluding papillary, sarcomatoid and other uncommon histological types were classified into 3 groups based on architectural variations. Statistically analyses were carried out for prognostic significance. Histological criteria of 3 groups were defined as follows. Group I consists predominantly of tubular formations with characteristic cystic change. Group III shows solid proliferation without tubular formations, and Group II shows small alveolar or trabecular structures with inconspicuous tubular formations. According to the survival curves (Kaplan-Meier method), the prognosis of Group I was significantly better than II and III. Ten year survival rate of each group was 88 +/- 7.8% in Group I, 39 +/- 8.8% in Group II, and 0% in Group III. The distribution of T and V stages in the 3 groups were not significantly different. Nuclear grading of Group I and II was not so different, though high grade cases predominated in Group III. Therefore, the present grading of alveolar type renal cell carcinoma based on architectural atypia was considered to be a useful prognostic parameter.

Aged↗

Granulocyte colony-stimulating factor, not granulocyte-macrophage colony-stimulating factor, co-operates with retinoic acid on the induction of functional N-formyl-methionyl-phenylalanine receptors in HL-60 cells.

The interaction of colony-stimulating factors (CSF) and retinoic acid (RA) in the proliferation and differentiation of HL-60 cells was examined. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated the proliferation of HL-60 cells in a dose-dependent manner at concentrations of 0.01-100 ng/ml; however, the proliferation due to GM-CSF was suppressed by 100 nM RA. Granulocyte colony-stimulating factor (G-CSF) slightly stimulated the proliferation of HL-60 cells at concentrations above 10 ng/ml. Neither G-CSF nor GM-CSF alone induced 12-o-tetra-decanoyl-phorbol-13-acetate (TPA)- or N-formyl-methionyl-phenylalanine (FMLP)-stimulated nitro-blue tetrazolium (NBT) reduction at concentrations of 0.01-100 ng/ml. G-CSF induced TPA- and FMLP-stimulated NBT reduction in the presence of 100 nM RA, but GM-CSF induced only TPA-stimulated NBT reduction. RA in addition to G-CSF synergistically increased FMLP binding to HL-60 cells, accompanied by increased NBT reduction in response to FMLP. RA in addition to GM-CSF markedly increased FMLP binding to HL-60 cells more than that induced by RA alone, but the combined treatment with RA and GM-CSF did not increase FMLP-stimulated NBT reduction more than that induced by RA alone. The results suggest that G-CSF stimulates RA-induced morphological and functional differentiation of HL-60 cells, but the differentiation-enhancing effects of GM-CSF are limited, whereas the growth-stimulating effect of GM-CSF on HL-60 cells is greater than that of G-CSF.

Cell Differentiation↗