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Biomedical subjects

Y Honma

Publications and source records attributed to Y Honma.

At least 181 records · Page 10Linked to original sources

Neuropeptide Y-immunoreactive structures in the telencephalon and diencephalon of the white sturgeon, Acipenser transmontanus, with special regard to the hypothalamo-hypophyseal system.

An immunohistochemical study using a streptavidin-biotin method demonstrated the extensive distribution of neuropeptide Y (NPY)-like immunoreactivity in the brain of the white sturgeon, Acipenser transmontanus, with the highest density in the basal telencephalon and diencephalon. Two labeled cell groups were found in the telencephalon, in mediobasal and dorsocaudal locations. Labeled fibers were considerably dense in the ventral area. The epithalamus displayed dense networks of varicose fibers in the ganglion habenulae, but only a few fibers were seen in the organon subcommissurale. In the thalamus, two groups of labeled cells were discerned in the periventricular gray matter: an anteroventral group largely composed of cerebrospinal fluid (CSF)-contacting neurons, and a dorsocaudal group consisting of non-CSF-contacting large neurons. The hypothalamus also contained a number of CSF-contacting neurons in the periventricular areas including the nucleus lobi inferioris, the nucleus lateralis tuberis and the nucleus recessus posterioris. Labeled varicose fibers were closely associated with the hypothalamo-hypophyseal complex, the organon vasculosum hypothalami, and the saccus vasculosus. Immunoreactive cells and fibers were also detected in the dorsal region of the adenohypophysis. These results suggest that NPY or a related molecule is involved in the hypothalamic neuroendocrine mechanisms of this primitive bony fish.

Animals↗

[Trial of self-management of outpatients with implanted reservoir for arterial infusion of anticancer drugs].

We attempted to instruct the outpatients with malignant liver tumor (metastatic liver cancer and advanced hepatocellular carcinoma) who received intermittent arterial infusion chemotherapy using implanted reservoir to detach the devices for arterial infusion by themselves at home. All patients who received our instruction could master self-detachment at home, which shortened the hospitalized day. And patients' desire for this treatment promoted with improvement of the recognition of their families to participate in treatment together. We experienced no trouble which disturb the treatment. This methods was considered to promote the improvement of QOL of these patients.

Ambulatory Care↗

[Usefulness of 2D FLASH multislice dynamic MR imaging for evaluation of parametrial invasion in cervical carcinoma].

Twenty seconds and 3 minutes after starting rapid injection of Gd-DTPA, multislice dynamic (MD) images were obtained with the 2 dimension fast low-angle shot (2D FLASH) technique. Four of 5 cervical carcinomas showed high signal intensity in the early dynamic phase (20 seconds), so they were readily distinguished from the myometrium that were not enhanced in the same phase. For evaluation of parametrial invasion, MD study showed better contrast between the tumor and the parametrium than did T2-weighted images because the tumor demonstrated a high signal intensity similar to that of the parameterium on T2-weighted images. MD images were able to scan the entire tumor especially in progressive cases and to evaluate the hemodynamics of the tumor. Therefore, MD imaging seemed to be useful for evaluation of parametrial invasion in cervical carcinomas.

Carcinoma, Squamous Cell↗

Differentiation of human monoblastic leukemia U937 cells induced by inhibitors of myosin light chain kinase and prevention of differentiation by granulocyte-macrophage colony-stimulating factor.

Inhibitors of protein kinase activities are useful for the study of intracellular signal transduction and some of these inhibitors are reported to induce differentiation of human leukemia cells. We examined effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with several kinase inhibitors on differentiation of human leukemia U937 cells. Nitroblue tetrazolium (NBT)-reducing activity, a typical marker of myelomonocytic differentiation, of U937 cells was induced by genistein and GM-CSF enhanced this activity. GM-CSF also induced the NBT-reducing activity of the cells in combination with 2,5-dihydroxycinnamic acid methyl ester, psi-tectorigenin and staurosporine, although each of them did not induce the activity. 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 in U937 cells NBT-reduction, and lysozyme and alpha-naphthyl acetate esterase activities. GM-CSF inhibited this differentiation and counteracted the anti-proliferation effect of the kinase inhibitors. These results suggest that some protein kinases are involved in differentiation of U937 cells and the kinases inhibited by ML-9 and ML-7 are associated with signal transduction of GM-CSF.

Azepines↗

Genistein exhibits preferential cytotoxicity to a leukemogenic variant but induces differentiation of a non-leukemogenic variant of the mouse monocytic leukemia Mm cell line.

Mouse leukemia Mm-A and Mm-S2 cells are subclones of mouse monocytic leukemia Mm cells, Mm-A cells having much higher leukemogenicity than Mm-S2 cells. The growth-inhibitory effects of several protein kinase inhibitors on leukemogenic Mm-A and non-leukemogenic Mm-S2 cells were examined. Most inhibitors of protein serine/threonine kinases inhibited the growth of Mm-A and Mm-S2 cells similarly, but some protein tyrosine kinase inhibitors exhibited differential inhibitory effects on Mm-A and Mm-S2 cells. Genistein inhibited growth of Mm-A cells more effectively than that of Mm-S2 cells, but another inhibitor of tyrosine kinase, herbimycin A, preferentially inhibited growth of non-leukemogenic Mm-S2 cells. Genistein induced or enhanced several differentiation markers of Mm-S2 cells, such as cell spreading, immunophagocytosis, nitroblue tetrazolium (NBT) reduction and lysozyme activity in a dose-dependent manner, but herbimycin A did not. Genistein was cytotoxic to Mm-A cells rather than inducing cell differentiation. Genistein has effects on several other cellular events as well as inhibition of tyrosine kinases. However, it effectively inhibited protein tyrosine phosphorylation in Mm-A cells and its decrease of tyrosine phosphorylation was closely associated with its inhibition of cell growth. Thus, a genistein-sensitive tyrosine kinase(s) may play an important role in the growth and/or survival of leukemogenic Mm-A cells.

Animals↗

Inhibition of granulocytic differentiation of acute promyelocytic leukemia cells in primary culture by transforming growth factor-beta.

We investigated the effect of transforming growth factor-beta 1 (TGF beta) on the proliferation and differentiation of cultured acute promyelocytic leukemia (APL) cells with the chromosomal t(15;17) translocation obtained from four patients to determine the role of TGF beta on growth and differentiation of APL cells. DNA synthesis, determined by 3H-thymidine uptake, was inhibited in the presence and absence of granulocyte colony-stimulating factor (G-CSF) in a dose-dependent manner by TGF beta in APL cells obtained from three of the four cases. TGF beta and G-CSF did not significantly affect the differentiation of APL cells, but all-trans retinoic acid (RA) induced morphological and functional differentiation in all APL cells tested. G-CSF markedly enhanced RA-induced granulocytic differentiation in APL cells obtained from all four cases. In cells in which TGF beta inhibited DNA synthesis, it also inhibited RA-induced granulocytic differentiation of APL cells and, to a greater degree, granulocytic differentiation induced by RA plus G-CSF. These results suggest that TGF beta is a negative regulator of the proliferation and differentiation of APL cells. The significance of TGF beta as an endogenous regulator in differentiation therapy with RA of APL patients is discussed.

Adult↗

Characterization of Vibrio cholerae O139 synonym Bengal isolated from patients with cholera-like disease in Bangladesh.

Vibrio cholerae O139 (synonym Bengal), a novel serovar of V. cholerae, is the causative agent of large outbreaks of cholera-like illness currently sweeping India and Bangladesh. Eight randomly selected V. cholerae O139 isolates were studied for their biological properties, which were compared with those of V. cholerae O1 and other V. cholerae non-O1. The V. cholerae O139 isolates were characterized by the production of large amount of cholera toxin, hemagglutination, weak hemolytic properties, resistance to polymyxin B, lysogeny with, and production of, kappa type phage (4/8 isolates only), and resistance to both classical and El Tor-specific phages. Thus, V. cholerae O139 isolates had an overall similarity with V. cholerae O1 El Tor.

Bangladesh↗

Characterization of the endothelin receptor in primary cultures of human aortic smooth muscle cells.

We characterized the endothelin receptor subtypes in primary cultures of human aortic smooth muscle cells (HASMCs) by binding studies. [125I]-Endothelin (ET)-1 saturation experiments showed the existence of a homogeneous population of binding sites with the high affinity (KD value) of 97 +/- 37 pM and maximum number of binding sites (Bmax) of 54 +/- 10 fmol/mg protein. However, almost no specific [125I]-ET-3 binding was observed. Inhibition of [125I]-ET-1 binding in the HASMCs membrane by nonlabeled compounds showed the following order of effectiveness: ET-1 = ET-2 = FR139317 >> ET-3. These results suggest that the endothelin receptor of HASMCs is of the ETA type. We also studied the effect of ET-1 on the cytosolic [Ca2+]i in HASMCs loaded with fura-2/AM. In 1.3 mM Ca2+, ET-1 produced a dose-dependent, biphasic increase in signal with a maximal effect at 10 nM. At this concentration, ET-1 produced a transient increase in [Ca2+]i that reached a peak at 1 min, which was followed by a slow but sustained increase in [Ca2+]i. This second phase was attenuated in Ca(2+)-deficient medium. Furthermore, ET-1 increased inositol 1,4,5-triphosphate in a time- and dose-dependent manner. These results suggest that the endothelin receptors of HASMCs are of the ETA type, which couple with Ca2+ channels.

Aorta↗

[Assessment of the quality of life of prostate cancer patients].

Assessing the QOL in cancer clinical trials is becoming increasingly important. However, a suitable device of assessment of QOL has not been developed yet for prostate cancer patients in Japan. We tried to assess the QOL of prostate cancer patients using the EORTC questionnaire translated in Japanese, and examined its validity and reliability. Thirty-six patients filled in a questionnaire. The reliability of this device was confirmed by the results of test-retest reproducibility. Good correlation was shown between the results and patients performance status, and between the results and clinical stages, which support the validity of the device. As for the results of assessment of QOL, these patients were severely damaged in sexuality. Those factors of functional status, physical symptoms and fatigue/malaise were closely related to disease activity and clinical stage.

Aged↗

[Role of cytokines in differentiation therapy with retinoic acid].

It is now clear that retinoic acid (RA) can induce complete remission in a high proportion of patients with acute promyelocytic leukemia (APL). The remission is apparently induced via the differentiating effects of RA, based on the appearance of increasing differentiated cells in the circulation and bone marrow. However, sometimes transient hyperleukocytosis develops after 1 to 2 weeks of therapy. To understand the hyperleukocytosis, we examined effects of some growth-promoting cytokines on proliferation of RA-treated APL cells in primary culture. Effect of negative regulators was also examined. These results indicate that proliferation of APL cells is greatly modulated by several cytokines even in the presence of RA. Enhanced RA-induced differentiation, when used in combination with other agents, has been shown with several cytokines, including granulocyte colony-stimulating factor and interferon alpha. The potential therapeutic use for RA in combination with interferon alpha is discussed.

Cell Differentiation↗

Differentiation of human myeloblastic leukemia ML-1 cells into macrophages by staurosporine, an inhibitor of protein kinase activities.

Protein kinase activities are involved in cellular proliferation and differentiation, and inhibitors of these activities are useful for studying the mechanisms of induction of differentiation. We found that staurosporine, an inhibitor of protein kinase activities, induced morphological differentiation of human myeloblastic leukemia ML-1 cells along myelomonocytic lineage and also induced functional differentiation (increase in nitroblue tetrazolium-reducing and lysozyme activities) in the cells. Several other protein kinase inhibitors such as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), sphingosine, N-(6-aminoethyl)-5-chloro-1-naphthalenesulfonamide and 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) did not induce the differentiation of ML-1 cells. Treatment with staurosporine induced formation of granules in ML-1 cells, and the granules showed metachromasia by toluidine blue staining; however, histamine content did not increase. The "metachromatic" ML-1 cells were positive for CD14, indicating that staurosporine induced the differentiation of ML-1 cells into metachromatic monocytes/macrophages, 1 alpha,25-dihydroxyvitamin D3 (VD3) enhanced appearance of metachromatic granules in staurosporine-treated cells. These results suggest that modulation of protein phosphorylation by a staurosporine-sensitive protein kinase(s) may be associated with differentiation of ML-1 leukemia cells.

Alkaloids↗

Inhibition of Abelson oncogene function by erbstatin analogues.

The authors examined the effect of a tyrosine kinase inhibitor, erbstatin, and its analogues on abl oncogene functions. Erbstatin and its stable analogue methyl 2,5-dihydroxycinnamate (2,5-MeC) inhibited the growth of v-ablts-NIH3T3 cells at the permissive temperature (33 degrees C) at lower concentrations than at the non-permissive temperature (39 degrees C). 2,5-MeC inhibited the morphological transformation and the activation of v-abl tyrosine kinase by the temperature shift (39 degrees C to 33 degrees C) more effectively than erbstatin. Previously the authors reported that erbstatin induced erythroid differentiation of K562 human chronic myelogenous leukaemia cells, so they examined the effect of erbstatin analogues on the erythroid differentiation. Among eight erbstatin analogues studied, ethyl 2,5-dihydroxycinnamate induced erythroid differentiation of K562 cells most effectively. Ethyl 2,5-dihydroxycinnamate also inhibited bcr-abl tyrosine kinase. These results indicate that the stable analogues of erbstatin suppress oncogene functions of Abl by inhibiting its tyrosine kinase.

Abelson murine leukemia virus↗

[Clinical pharmacology and efficacy of S-1108].

We studied the pharmacokinetics of a new cephem antibiotic, S-1108, in patients with impaired kidney functions. Serum and urinary levels of S-1006 were determined after oral administration of S-1108 at 150 mg to 9 patients with renal dysfunction. In patients with severe renal impairment, high serum levels were maintained over long periods of time. Urinary excretion rates of S-1006 were lower as degrees of kidney failure were severer. S-1108 was administered to treat 27 patients with respiratory tract infections, and its clinical efficacy and safety were evaluated. The clinical efficacies were good in 26 patients, but poor in 1, yielding an efficacy rate of 96.3%. As to adverse reactions; diarrhea was observed in one case. Laboratory tests revealed elevated GOT and GPT in 1, and elevated gamma-GTP in another. These abnormalities, however, were slight and no severe side effects were caused by the drug.

Administration, Oral↗

Synthesis of active metabolite(s) from 1 alpha-hydroxyvitamin D3 by human monocytic leukemia cells.

Synthesis of the biologically active metabolite(s) from 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3) was examined in various types of human leukemia cell lines. Untreated monocytoid leukemia cells (U937 and HEL/S) metabolized 1 alpha (OH)D3 to the active metabolite(s), possibly 1 alpha, 24- and/or 1 alpha, 25-dihydroxyvitamin D3, and these cells were efficiently induced to differentiate by treatment with 1 alpha (OH)D3. However, the other types of leukemia cells did not efficiently metabolize it and were not induced to differentiate by 1 alpha (OH)D3. The possible therapeutic advantage of 1 alpha (OH)D3 in the treatment of monocytic leukemia is discussed.

Humans↗

Herbimycin A, an inhibitor of tyrosine kinase, prolongs survival of mice inoculated with myeloid leukemia C1 cells with high expression of v-abl tyrosine kinase.

Herbimycin A, a benzoquinonoid ansamycin antibiotic, reduces intracellular phosphorylation by some tyrosine kinases, including v-abl. The mouse megakaryoblastic cell line C1 expresses v-abl protein at high levels. Herbimycin A at about 20 ng/ml caused 50% inhibition of growth of C1 cells but at 100 ng/ml scarcely affected the growth of another mouse leukemia cell line, M1 cells, or of normal bone marrow cells. Injection of 10(6) C1 cells into nude mice resulted in death of all the mice within 30 days. Administration of herbimycin A significantly enhanced the survival of mice inoculated with C1 cells but scarcely affected the survival of mice inoculated with M1 cells. These results suggest that herbimycin A and/or related compounds may be useful for treatment of some types of leukemia in which tyrosine kinase activity is implicated as a determinant of the oncogenic state.

Animals↗

[2D time of flight stereoscopic MR angiography of pulmonary vessels].

Two-dimensional (2D) time-of-flight (TOF) stereoscopic MR angiographies (MRA) of the pulmonary vessels were obtained from 15 healthy volunteers and five patients with pulmonary cancer in the mediastinum and pulmonary hilum. Fifteen healthy volunteers were examined using FLASH (Fast Low Angle Shot) with breath holding (40/8/40, TR/TE/flip angle). Except for the left superior pulmonary vein, pulmonary vessels in the mediastinum and hilum were well defined on stereoscopic MRA images. Although it was difficult to define the pulmonary arteries in the peripheral zone, intersegmental veins were easily defined with this method. In five cases of pulmonary cancer that were confirmed to show definite tumor involvement of the pulmonary vessels in the mediastinum and hilum by enhanced CT and MRI (SE method), irregular narrowing and interruption of the vessels were shown on MRA. In conclusion, 2D TOF stereoscopic MRA is considered a noninvasive, effective method for evaluation of the morphology of pulmonary vessels adjacent to the tumor in the mediastinum and hilum.

Adenocarcinoma↗