Biomedical subjects

Y Honma

Publications and source records attributed to Y Honma.

At least 127 records · Page 7Linked to original sources

PubMed1997

AML1a but not AML1b inhibits erythroid differentiation induced by sodium butyrate and enhances the megakaryocytic differentiation of K562 leukemia cells.

AML1 may play a role in growth and differentiation of cells along erythroid and/or megakaryocytic lineages, because a significant level of the AML1 gene is expressed in these cells. We overexpressed AML1a (without the transcription-activating domain) and AML1b (with the domain) proteins in K562 leukemia cells, which can be induced to differentiate into hemoglobin-producing cells and megakaryocytes. The AML1a-transfected K562 cells had a reduced capacity to differentiate in the presence of sodium n-butyrate but not in the presence of other inducers, such as hemin, 1-beta-D-arabinofuranosylcytosine, and herbimycin A. The AML1 antisense oligodeoxynucleotide but not the sense oligomer recovered its differentiation-inducing capacity in the presence of butyrate. On the other hand, AML1b conferred a similar differentiation-inducing capacity upon K562 cells transfected with vector alone. AML1a expression was associated with enhanced sensitivity to megakaryocytic differentiation induced by phorbol ester. These results provide evidence that AML1 proteins play a role in erythroid and megakaryocytic differentiation.

Antigens, CD↗

PubMed1997

Digitalization of the mother in treating hydrops fetalis in monochorionic twin with Ebstein's anomaly. Case report.

Hydrops fetalis thought to be due to Ebstein's anomaly was seen at 22 weeks' gestation in one of two fetuses with a monochorionic placenta. Hydrops was treated with maternal digitalization and resolved by the 28th week of gestation. Hydrops did not recur while maternal digitalization continued. A clinical diagnosis of twin-to-twin transfusion syndrome required termination of the pregnancy at 33 weeks of gestation. The twin with Ebstein's anomaly died 22 hours after birth. The other twin survived and was normal at 19 months of age. Thus, administration of digitalis to the mother controlled hydrops fetalis in one fetus, and ultimately led to the survival of the healthy infant.

Adult↗

PubMed1997

Neplanocin A, a potent inhibitor of S-adenosylhomocysteine hydrolase, potentiates granulocytic differentiation of acute promyelocytic leukemia cells induced by all-trans retinoic acid.

Several neplanocin A analogs were synthesized and their growth-inhibiting and differentiation-inducing activities on myelogenous leukemia cells were examined. An adenosine kinase-ineffective analog of neplanocin A was effective in inducing differentiation, suggesting that phosphorylation of the nucleoside is not essential for inducing the differentiation of leukemia cells. Neplanocin A induced functional and morphological differentiation of HL-60 cells, but did not effectively induce differentiation of NB4, a cell line derived from a leukemia patient with t(15;17). However, these cells have been known to undergo granulocytic differentiation upon treatment with all-trans retinoic acid (ATRA), and are used as a model for differentiation therapy in acute promyelocytic leukemia. Preexposure of NB4 cells to low concentrations of neplanocin A greatly enhanced the ATRA-induced differentiation of the cells, whereas representative antileukemic drugs such as cytosine arabinoside and daunomycin did not enhance this differentiation. A clinical strategy that combines intermittent treatment with neplanocin A analogs and a low dose of ATRA may increase the clinical response and decrease the adverse effects of ATRA.

Adenosine↗

PubMed1996

Evaluation of the radiosensitizing effects of RK28 intravenous, intraarterial, and intratumoral injections on the rabbit VX2 tumor system.

PURPOSE: To evaluate the differences in the radiosensitizing effects of intravenous (i.v.) injection, intraarterial (i.a.) injection, and intratumoral (i.t.) injections of the hypoxic cell radiosensitizer RK28 ([1-(4'-hydroxy-2'-butenoxy)methyl-2-nitroimidazole], a 2-nitroimidazole with an acyclic sugar analogue substituted at the N-1 position of the imidazole ring) using an animal experimental system. METHODS AND MATERIALS: Rabbit VX2 tumors, which were implanted in the muscle of left hind legs and grown to 3 cm in diameter, were treated with RK28 (80 mg/kg x b.wt.) before 15 Gy of local x-ray irradiation. The auricular vein and the left saphenous artery were used for systemic injection and regional injection, respectively. For i.t. injection, a 21-gauge needle with three lateral holes was positioned in the central area of the tumor. Tumor regression was precisely evaluated by computed tomograpy (CT), and survival time was also studied. Using high-performance liquid chromatography (HPLC), pharmacokinetic studies for RK28 and its seven major metabolites were performed in tumor and serum at 0, 10, 20, 30, and 60 min after drug injection was completed. RESULTS: Radiosensitizing effects of RK28 were considered present after i.a. injection (p < 0.05) and i.t. injection (p < 0.05) after analyzing tumor volumes on day 21 after treatment. Increased survival was not observed in any group with RK28 injection compared with survival in the group treated by x-ray irradiation alone. Pharmacokinetic studies showed the average concentration of RK28 in the tumor during x-ray irradiation was 1.3 times higher after i.a. injection and 3.5 times higher after i.t. injection than that after i.v. injection. The time modifying factor50 (TMF50: ratio of time for tumor to decrease by 50%, radiation alone vs. radiation plus drug) was calculated to be 1.5 after i.v. injection, 1.7 after i.a. injection, and 2.3 after i.t. injection. The values of TMF50 correlated to the average concentrations of RK28 in the tumor. As to metabolites of RK28, beta-glucuronated compound and cysteine conjugate were highly detected. The concentrations of cysteine conjugate were higher in the tumor than in serum via i.v. injection. CONCLUSIONS: Radiosensitizing effects of RK28 were observed on the rabbit VX-2 tumor system after i.a. or i.t. injection. Pharmacokinetic studies proved that radiosensitizing effects depended on the concentration in the tumor, though the administration routes were different. Combined forms with nonprotein thiols were detected. However, survival benefits were not obtained by RK28. For clinical applications of RK28, i.a. or i.t. injection could facilitate better local control of cancer.

Animals↗

PubMed1996

Differentiation inhibitory factor nm23 as a new prognostic factor in acute monocytic leukemia.

Differentiation inhibitory factor (nm23 protein) inhibited the induction of differentiation of mouse myeloid leukemia M1 and WEHI-3BD+ and human erythroleukemia HEL, KU812, and K562 cells. Block of differentiation may be associated with the aggressive behavior of leukemia. To examine the role of nm23 in human myeloid leukemia, we investigated the relative levels of nm23-H1, nm23-H2, and c-myc transcripts in 42 patients with acute myelogenous leukemia (AML), and in 5 with chronic myelogenous leukemia at chronic phase by reverse transcriptase polymerase chain reaction. The expression of nm23-H1 and -H2 but not of c-myc in AML was significantly higher than that in normal blood cells. Among AMLs, acute monocytic leukemia (presentation with AML-M5 morphology) was especially associated with elevated nm23-H1 and -H2 mRNA levels. On the other hand, the elevated levels of c-myc expression in AML-M5 were less evident. An analysis of correlation between nm23 expression and clinicopathological parameters showed that resistance to initial chemotherapy is associated with increased nm23-H1 mRNA levels and that a high initial white blood cell count is associated with increased nm23-H2 mRNA levels. Elevated nm23-H1 mRNA levels were associated with significantly reduced the overall survival of AML, especially of AML-M5 patients. The present results indicate that nm23-H1 and -H2 are overexpressed in AML and especially nm23-H1 gene expression predicts the prognosis of AML, especially of AML-M5.

Animals↗

PubMed1996

Ontogenetic changes in neuropeptide Y-like-immunoreactivity in the terminal nerve of the chum salmon and the cloudy dogfish, with special reference to colocalization with gonadotropin-releasing hormone-immunoreactivity.

We observed ontogenetic changes of neuropeptide Y (NPY)-like-immunoreactivity in the terminal nerve (TN) of the chum salmon, a teleost, and the cloudy dogfish, an elasmobranch. In the chum salmon, NPY-like-immunoreactive (NPY-IR) cells first appeared in the olfactory placode of embryos at 16 days after fertilization, and then extended sequentially and centrally in the olfactory system. Colocalization of NPY- and gonadotropin-releasing hormone (GnRH)-like-immunoreactivities was also observed in TN ganglion cells. In the cloudy dogfish, NPY-IR cells first appeared in the rudimental TN ganglion of the embryo at the 40 mm stage. Then, the NPY-IR cells and fibers in the TN system increased in density during late embryonic periods. Colocalization of NPY- and GnRH-like-immunoreactivities in TN ganglion cells was not found in the developing or the adult dogfish.

Age Factors↗

PubMed1996

Enhancement of activity of 1alpha, 25-dihydroxyvitamin D3 for growth inhibition and differentiation induction of human myelomonocytic leukemia cells by tretinoin tocoferil, an alpha-tocopherol ester of all-trans retinoic acid.

Tretinoin tocoferil is an alpha-tocopherol ester of all-trans retinoic acid (RA) and safely used in the treatment of skin ulcer. Tretinoin tocoferil inhibited proliferation of human promyelocytic leukemia HL-60 cells and induced granulocytic differentiation of the cells, but less than RA. alpha-Tocopherol did not affect differentiation of HL-60 cells, but at high concentrations enhanced its nitroblue tetrazolium (NBT)-reducing activity and expression of surface antigen CD11b, which are markers of myelomonocytic differentiation induced by RA. Tretinoin tocoferil increased NBT reduction in HL-60 cells treated with RA. It also enhanced the differentiation of HL-60 cells induced by dimethyl sulfoxide, phorbol-12-myristate 13-acetate or 1alpha,25-dihydroxyvitamin D3 (VD3). In combination with a low concentration of VD3, it induced the NBT-reducing activity of human monoblastic U937 cells very effectively. Moreover, it enhanced the differentiation of human myelomonocytic ML-1, THP-1, P39/TSU, and P31/FUJ cells induced by VD3. In combination with VD3, it synergistically inhibited the proliferation of HL-60, U937, ML-1, THP-1, P39/TSU, and P31/FUJ cells and decreased the effective concentration of VD3 to a 10(-10) mol/L level. Because tretinoin tocoferil was reported to induce neither retinoid-related toxicity nor teratogenicity, the therapeutic advantage of the use of it in treatment of myelomonocytic leukemia is suggested.

Antineoplastic Agents↗

PubMed1996

2-[(2-Aminobenzyl)sulfinyl]-1-(2-pyridyl)-1,4,5,6-tetrahydrocyclopent[d]imidazoles as a novel class of gastric H+/K+-ATPase inhibitors.

Substituted 2-sulfinylimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K(+)-ATPase. The 4,5-unsubstituted imidazole series 6-11 and the 1,4,5,6-tetrahydrocyclopent[d]imidazole series 12 were found to be potent inhibitors of the acid secretory enzyme H+/K(+)-ATPase. Structure-activity relationships indicate that the substitution of 2-pyridyl groups at the 1-position of the imidazole moiety combined with (2-aminobenzyl)-sulfinyl groups at the 2-position leads to highly active compounds with a favorable chemical stability. Other substitution patterns in the imidazole moiety result in reducing biological activities. 2-[(2-Aminobenzyl) sulfinyl]-1-[2-(3-methylpyridyl)]-1,4,5,6-tetrahydrocyclopent++ ++ ++ [d]-imidazole (12h, T-776) was selected for further development as a potential clinical candidate. Extensive study on the acid degradation of 12h indicates a mechanism of action different from that of omeprazole, the first H+/K(+)-ATPase inhibitor introduced to the market.

Animals↗

PubMed1996

Effect of Vibrio cholerae non-O1 protease on lysozyme, lactoferrin and secretory immunoglobulin A.

The effect of Vibrio cholerae non-O1 protease on host defense proteins (lysozyme, secretory immunoglobulin A and lactoferrin) was studied in relation to its virulence mechanism. The proteins treated with the protease were analysed by SDS-PAGE. There was no influence of the protease on lysozyme. The protease cleaved lactoferrin into two fragments of 50 kDa and 34 kDa. N-terminal amino acid sequencing of these fragments revealed that the cleavage site was near the hinge region, between serine 420 and serine 421. This cleavage could affect the transition from open to closed configuration which is involved in iron binding and release. The anti-bacterial activity of lactoferrin was not affected by protease treatment. Secretory immunoglobulin A yielded a 42-kDa protein as the cleavage product. The susceptibility of secretory immunoglobulin A to V. cholerae non-O1 protease suggests a mechanism by which bacteria might evade the effect of this immunoglobulin.

Amino Acid Sequence↗

PubMed1996

Immunohistochemical and Ultrastructural characterization of the terminal nerve ganglion cells of the ayu, Plecoglossus altivelis (Salmoniformes, Teleostei).

BACKGROUND: Little is known on the cytological properties of the terminal nerve ganglion (TNG) cells in teleosts (Demski, 1993. Acta Anat., 148:81-95). MATERIALS AND METHODS: To characterize the TNG cells of a salmonoid fish, Plecoglossus altivelis, we adopted immunohistochemistry and transmission electron microscopy (TEM). RESULTS: The majority of the TNG cells formed a compact mass halfway between the olfactory sac and the olfactory bulb, whereas a few cells were scattered in the ventromedial region of the olfactory bulb. The cell had a voluminous perikaryon that was positive to antisera against gonadotropin-releasing hormone (GnRH), molluscan cardioexcitatory tetrapeptide (FM-RFamide), and neuropeptide Y (NPY). Immunostaining of consecutive sections with each antiserum showed the coexistence of these antigens in the same cells and their processes. Most of the processes originating from the cells projected centrally to the basal forebrain, including the optic nerve. With TEM, the cells revealed a peptidergic nature, i.e., the presence of abundant granular endoplasmic reticula and well-developed Golgi bodies in association with vesicles that were 70-100 nm in diameter. Occasionally, the cells adjoined one another directly without the intervention of glial sheets. Synaptic contacts were frequent in the proximal region of the processes, where thin lateral processes of the cells and axon terminals of unknown origin were intermingled with each other. Terminal buttons being engulfed by the soma were commonly seen. CONCLUSIONS: The TNG cells of the salmonoid fish share many cytological characteristics with the cells of the nucleus olfactoretinalis of advanced teleosts such as acanthopterygians.

Animals↗

PubMed1996

Angelmicin B, a new inhibitor of oncogenic signal transduction, inhibits growth and induces myelomonocytic differentiation of human myeloid leukemia HL-60 cells.

Angelmicin B is a new microbial substance which inhibits src tyrosine kinase activity and oncogenic signal transduction. We investigated the effect of angelmicin B on the proliferation and differentiation of the HL-60 human myeloid leukemia cell line. Angelmicin B caused the dose-dependent inhibition of cell proliferation and induction of differentiation along the myelomonocytic pathway, as determined by morphological changes, nitroblue tetrazolium (NBT) reduction, and non-specific esterase and lysozyme activities at concentrations ranging from 0.1 to 0.5 microgram/ml. Also, it induced significantly the differentiation of mouse myeloid leukemia M1 cells. A similar concentration of angelmicin B inhibited the growth of the myeloid leukemia cell lines K562, HEL, KU812, ML-1, U937 and THP-1, but did not induce differentiation of these cells significantly. The differentiation of HL-60 cells was enhanced by combined treatment with angelmicin B and 1 alpha, 25-dihydroxyvitamin D3 (VD3), retinoic acid or tumor necrosis factor-alpha (TNF alpha). Angelmicin analogs (A1, A2, B, C and D) had almost equivalent effects on the differentiation of HL-60 cells, although angelmicins C and D inhibited src tyrosine kinase activity less than the other analogs. The effective concentrations of angelmicin B in src kinase inactivation was about 100-fold higher than those required for the growth inhibition and differentiation induction. These findings indicate that the differentiation-inducing activity of angelmicins is not associated with their src kinase-inhibiting activity, and may be associated with the modulation of other signal pathway(s).

Animals↗

PubMed1996

Ethacrynic acid and 1 alpha,25-dihydroxyvitamin D3 cooperatively inhibit proliferation and induce differentiation of human myeloid leukemia cells.

The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 (VD3), inhibits proliferation and induces differentiation of leukemia cells, but its clinical use is limited by the adverse effect of hypercalcemia. In this study we found that the loop diuretic ethacrynic acid, which is used to treat hypercalcemia, enhanced the differentiation of human leukemia cells induced by VD3. Ethacrynic acid alone inhibited the proliferation of human promyelocytic HL-60 cells while only slightly increasing differentiation markers such as nitroblue tetrazolium (NBT)-reducing and lysozyme activities. Ethacrynic acid effectively enhanced the growth-inhibiting action of VD3. In the presence of ethacrynic acid, VD3 increased the NBT-reducing and lysozyme activities and the CD11b expression of HL-60 cells more effectively than VD3 alone. Other loop diuretics, furosemide and bumetanide, also enhanced the differentiation of HL-60 cells induced by VD3, but to a lesser extent than ethacrynic acid. The differentiation of HL-60 cells induced by all-trans retinoic acid, dimethyl sulfoxide or phorbol-12-myristate 13-acetate was also enhanced by ethacrynic acid with increasing NBT-reducing and lysozyme activities and the expression of CD11b or CD14 surface antigen. Morphologically, ethacrynic acid enhanced the monocytic differentiation of HL-60 cells induced by VD3 and phorbol ester and the granulocytic differentiation by retinoic acid and dimethyl sulfoxide. Other human myelomonocytic leukemia ML-1, U937, P39/TSU and P31/FUJ cells were induced to differentiate by VD3 and this was also enhanced by ethacrynic acid. The long-term culture of HL-60 cells showed that ethacrynic acid plus VD3 induced the complete growth arrest of HL-60 cells. Therefore ethacrynic acid, which is used to treat hypercalcemia, enhanced the proliferation-inhibiting and differentiation-inducing activities of VD3 and the combination of ethacrynic acid and VD3 may be useful in therapy for myeloid leukemia.

Calcitriol↗

PubMed1996

Enhancement of sensitivity of human lung adenocarcinoma cells to growth-inhibitory activity of interferon alpha by differentiation-inducing agents.

A low concentration of differentiation inducers such as dimethylsulphoxide (DMSO), sodium butyrate, hexamethylene bisacetamide and sodium phenylacetate greatly enhanced the antiproliferative effect in vitro and in vivo of interferon alpha (IFN-alpha) to several human lung adenocarcinoma cells. The agents induced morphological changes in the adenocarcinoma cells and the agents together with IFN-alpha-induced alkaline phosphatase activity, which is a typical marker of type II pneumocyte maturation. To understand the mechanism of the DMSO-enhanced interferon sensitivity, we examined the effect of DMSO on high-affinity IFN-alpha receptor and interferon-stimulated promoter-binding factors. The lung adenocarcinoma cells were not impaired in IFN-alpha receptor and interferon-stimulated gene transactivation factor 3 (ISGF-3). Our data suggest that the enhancement of interferon sensitivity in the lung adenocarcinoma cells acts downstream of the activation of ISGF-3.

Acetamides↗

PubMed1996

Cloning and genetic analysis of the Vibrio cholerae aminopeptidase gene.

The structural gene for the Vibrio cholerae leucine aminopeptidase (lap) was cloned and sequenced. The cloned DNA fragment contained a 1,503-bp open reading frame potentially encoding a 501-amino-acid polypeptide with a calculated molecular mass of 54,442 Da. The deduced amino acid sequence of the entire protein showed high homology with the sequence of Vibrio proteolyticus leucine aminopeptidase. The residues potentially involved in binding the zinc ions were completely conserved in the V. cholerae aminopeptidase as well as in the V. proteolyticus aminopeptidase. The recombinant protein was partially purified and characterized. The molecular mass was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be 34 kDa, suggesting a processing of the protein to acquire the mature form. The protease showed maximum activity at pH 9.0 and was thermostable at 70 degrees C. The substrate leucyl-p-nitroanilide was cleaved by the protease, and its activity was inhibited by EDTA and bestatin. These results suggested that the protein was a leucine aminopeptidase. The PCR analysis of lap gene distribution showed that it was widely distributed among the V. cholerae strains. It was not present in the other species examined.

Amino Acid Sequence↗

PubMed1996

Distribution of neuropeptide Y and gonadotropin-releasing hormone immunoreactivities in the brain and hypophysis of the ayu, Plecoglossus altivelis (Teleostei).

This paper reports on the distribution, relationship and seasonal variations of neuropeptide Y (NPY)-like and gonadotropin-releasing hormone (GnRH)-like immunoreactants in the brain and hypophysis of the bony fish, the ayu Plecoglossus altivelis. NPY-like immunoreactivity was widely distributed in the brain: labeled cells were found in the nervus terminalis, the nucleus entopeduncularis, the habenula, the nucleus preopticus periventricularis, the nucleus tuberis lateralis, the mediodorsal hypothalamus, the dorsal tegmentum, and other sites. NPY fibers were considerably dense in the telencephalon and hypothalamus, and innervated the hypophysis. GnRH-positive cells occurred in the nervus terminalis and were sparsely distributed in the preoptic and tuberal areas of the hypothalamus. GnRH fibers were found in various regions of the brain. They were relatively dense in the hypothalamus, showing a local concentration in the middle region of the neurohypophysis. The GnRH-positive cells and fibers in the hypothalamo-hypophyseal complex increased in density around the spawning season. In tandem with gonadal maturation, NPY labeling in the cells of the nucleus tuberis lateralis became intense concomitantly with an increase in the labeled varicosities in the middle region of the neurohypophysis. Double immunostaining showed that NPY fibers were closely apposed to GnRH cells in the preoptic area. These results suggest a correlative involvement of NPY and GnRH in the control of the hypophyseal gonadotropic function of the ayu.

Animals↗

PubMed1996

Hemorrhagic pituitary adenoma manifesting as transient global amnesia.

A 68-year-old female presented with recurrent transient global amnesia due to hemorrhagic prolactin-producing pituitary adenoma. Magnetic resonance imaging clearly revealed the anatomical relationship between the hematoma, within the parasellar tumor, and the compressed medial temporal lobe of the right (non-dominant) hemisphere. Within 4 weeks after the start of bromocriptin administration, the adenoma had markedly regressed and the affected temporal lobe was decompressed. She has experienced no further episode of transient global amnesia. Magnetic resonance imaging is recommended to detect latent organic lesions responsible for transient global amnesia, although the disorder is considered to be benign and of functional origin.

Aged↗

PubMed1996

Intramedullary spinal cord and brain metastases from thyroid carcinoma detected 11 years after initial diagnosis--case report.

A 60-year-old male presented with a rare intramedullary spinal cord metastasis from thyroid carcinoma manifesting as rapidly worsening motor and sphincter disturbances. The primary tumor had been treated 11 years previously. Magnetic resonance imaging clearly revealed the hemorrhagic tumor localized in the thoracic spinal cord and an associated, asymptomatic metastasis in the cerebellum. The hypervascular tumors were totally removed. The histological diagnosis was papillary adenocarcinoma. He has been stable for 2 years postoperatively. Surgical resection of intramedullary metastasis should be considered in patients with less malignant tumors such as thyroid carcinoma, especially when accompanied by progressive compression myelopathy.

Brain Neoplasms↗

PubMed1996

Induction of differentiation and enhancement of vincristine sensitivity of human erythroleukemia HEL cells by vesnarinone, a positive inotropic agent.

We examined the effect of vesnarinone, an oral cardiotonic, on the growth and differentiation of human myeloid leukemia cells. Vesnarinone alone markedly induced erythroid differentiation of HEL cells. All-trans-retinoic acid also induced erythroid differentiation of the cells, and the differentiation was greatly enhanced by combined treatment with vesnarinone and retinoic acid. HEL cells are highly resistant to some anticancer drugs, including vincristine, but treatment with vesnarinone greatly increased the sensitivity of HEL cells to vincristine. Enhancement of vincristine sensitivity by vesnarinone was not as significant for other leukemia cells. Expression of P-glycoprotein in HEL cells was effectively inhibited by vesnarinone, suggesting that the restoration of vincristine sensitivity is associated with decrease of P-glycoprotein expression in HEL cells. The plasma level of vesnarinone required to induce differentiation of leukemia cells is 30 micrograms/mL, which could be achieved with oral administration. These results suggest that vesnarinone should be useful in differentiation therapy for some types of myelogenous leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗