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Biomedical subjects

H Ueno

Publications and source records attributed to H Ueno.

At least 307 records · Page 17Linked to original sources
PubMed1996

Antitumor activities of combined treatment with a novel immunomodulator, (2S,3S,4R)-1-O-(alpha-D-Galactopyranosyl)-2-(N-Hexacosanoylamino)-1,3,4 - octadecanetriol (KRN7000), and radiotherapy in tumor-bearing mice.

The novel immunomodulator (2S,3S,4R)-I-O-(alpha-D-galactopyranosyl)-2- (N-hexacosanoylamino)-1,3,4-octadecanetriol (KRN7000) in combination with high-dose (20 and 30 Gy) local x-ray irradiation or low-dose (3 Gy) fractionated whole-body irradiation showed significantly stronger antitumor activities against Meth A-and Colon26-bearing mice than treatments by radiation or KRN7000 alone, and 60% of mice in combination treatment groups were cured. Furthermore, the results of tests rechallenging the cured mice with Meth A and Colon26 cells strongly suggested that tumor-specific immunity was induced by the combination treatment. The suggestion was supported by the result that the systemic administration of KRN7000 could produce large amounts of interleukin-2 and interferon-gamma, which contribute to induction of tumor-specific cytotoxic lymphocytes not only in normal mice but also in whole-body irradiated mice. Furthermore, it was also suggested that KRN7000 contributes to protecting antitumor effector cells, such as natural killer cells, from impairments caused by radiation. Taking together the results and the knowledge that tumor-specific cytotoxic lymphocytes play a critical role in prevention of tumor recurrence and distant metastasis, it is strongly suggested that combined therapy with KRN7000 and radiation could be quite useful for cancer treatment.

Adjuvants, Immunologic↗
PubMed1996

[Prevention and treatment of postoperative septic MOF and DIC and efficacy of blood purification].

Pathophysiologic concept of SIRS has been proposed for the better management of postoperative severe infection and septic MOF, and the concept has been found to be very useful. It is very important to identify the high risk SIRS patients of the development of septic MOF and to treat those patients aggressively to prevent the development of septic MOF. In the prevention and treatment of septic MOF, the blood purification has been found to be very effective. Among the blood purifications, continuous blood purification, such as continuous hemodiafiltration (CHDF) should be chosen for this purpose. CHDF has been claimed to be very effective to removal of causative humoral mediators from the blood stream. The concept of DIC has been changed recently and the concept of DII (disseminated intravascular inflammation) should be applied instead of DIC, since the main feature of this pathologic condition is the damage of endothelial cells due to extensive systemic inflammation.

Disseminated Intravascular Coagulation↗
PubMed1996

[An examination of two reporting methods of falls among the elderly living in the community].

This study examined the concordance of two reporting methods for falls (3 month and 12 month recall) experienced by elderly living in a rural community. Four interview surveys on the occurrence of falls over a 3 month period were conducted from 1992 to 1993 every three months. In the final interview, subjects were also asked about the occurrence of falls during the past 12 months. A total of 799 subjects (270 men, 529 women) aged 65 and over, living in a village of Niigata Prefecture, responded to all four surveys. The incidence of falls in one year was 19.0% by the 3 month recall, and 19.1% by the 12 month recall. Overall agreement of fall occurrence between the two methods was 98.9%, and a coefficient of kappa as a measure of concordance was 0.96. On the other hand, subjects who sustained injuries during falls reported in the 3 month reporting did not necessarily recall having a fall when interviewed at the end of the study. In any case, this study reveals that for surveying falls by the elderly living in the community a 1 year recall is a reliable method, because of the high agreement of fall occurrence when comparing the two methods.

Accidental Falls↗
PubMed1996

Enhancing effects of (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-2-(N-hexacosanoylamino) -1,3,4-octadecanetriol (KRN7000) on antigen-presenting function of antigen-presenting cells and antimetastatic activity of KRN7000-pretreated antigen-presenting cells.

(2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-2-(N-hexacosanoylamino)- 1,3, 4-octadecanetriol (KRN7000), with an alpha-galactosylceramide structure, is an immunomodulator showing potent antimetastatic activities. In an in vitro study, KRN7000 potently stimulated proliferation and enhanced natural killer activity in spleen cells from BALB/c euthymic mice, but not BALB/c athymic (nu/nu) mice, suggesting that T cells play an important role in these activities. To study the detailed immunostimulatory mechanisms of KRN7000, syngeneic mixed leukocyte reactions were then performed using dendritic cell-enriched fractions (DCEFs) from spleens of BALB/c euthymic and athymic mice. In these studies, KRN7000 enhanced the antigen-presenting cell activities of the DCEFs. In addition, marked production of interleukin-2 and interferon-gamma in BALB/c euthymic mice was observed following treatment with KRN7000 in vitro and in vivo. Because of these strong immunostimulating effects of KRN7000, its antimetastatic effects were also evaluated. Adoptively transferred KRN7000-treated DCEF markedly prolonged the survival time of mice bearing B16 pulmonary metastases. These results demonstrate that KRN7000 may be useful for cancer therapy not only as an antitumor agent but also as an activator of antigen-presenting cells such as dendritic cells, which can be used for adoptive cellular therapy.

Adjuvants, Immunologic↗
PubMed1996

Telomerase activity in gynecological tumors.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends using an RNA component as a template. Extension of telomeric repeats by telomerase prevents telomere shortening with cell divisions and contributes to chromosomal stability, possibly leading to immortalization of the cells. In the present study, we determined the telomerase activity of gynecological tumors and cell lines using a newly developed non-radioisotope telomeric repeat amplification protocol. A total of 21 cell lines derived from cervical cancer, endometrial cancer, ovarian cancer, and choriocarcinoma was examined, and all lines were found to be positive for telomerase activity, although the activity varied among cell types. A total of 50 gynecological malignant tumors was also examined, and 10 of 12 (83%) cervical cancers, 12 of 13 (92%) endometrial cancers, 18 of 21 (86%) ovarian cancers, 2 of 2 tubal cancers, and 1 of 1 vulvar cancer were found to be positive for telomerase activity. A total of 88% of gynecological tumors tested was thus found to be telomerase positive. However, no significant correlation was observed between telomerase activity and clinical features for any tumor type, although ovarian tumors expressing high telomerase activity tended to be more invasive. In contrast to that in malignant tumors, telomerase expression was weak and less common in premalignant lesions, with 5 of 7 cervical intraepithelial lesions and 4 of 6 borderline ovarian tumors exhibiting faint activity. Nine benign uterine lesions were also examined, and all were negative for telomerase activity except 1 uterine myoma, which had a weak signal. Three benign ovarian cysts examined had weak telomerase activity. These findings suggest that telomerase activation is common in gynecological malignant tumors and may be a critical step in their pathogenesis. However, premalignant lesions and some types of benign tumors also express weak telomerase activity.

Female↗
PubMed1995

TPO/c-mpl ligand induces tyrosine phosphorylation of multiple cellular proteins including proto-oncogene products, Vav and c-Cbl, and Ras signaling molecules.

Thrombopoietin (TPO)/c-mpl ligand is a hematopoietic growth factor that stimulates proliferation and maturation of megakaryocytes. To analyze the signaling pathway downstream of the c-mpl product, we used a human megakaryoblastic cell line, Mo7e, that has been proved to be responsive to TPO in terms of DNA synthesis. In this study, we found that TPO treatment resulted in tyrosine phosphorylation of Jak-2 kinase. Moreover, it was revealed that several functional molecules involved in the Ras signaling pathway, Shc and Sos, were phosphorylated by treatment with TPO. Finally, tyrosine phosphorylation of the proto-oncogene products, Vav and c-Cbl, has been proved to be induced by TPO. These results suggest that TPO could activate several signaling pathways including the Jak/Stat pathway, the Ras pathway and possibly another pathway involving the c-Cbl proto-oncogene product.

Cell Cycle Proteins↗
PubMed1995

An epidermal growth factor receptor-leukocyte tyrosine kinase chimeric receptor generates ligand-dependent growth signals through the Ras signaling pathway.

Leukocyte tyrosine kinase (LTK) is a receptor tyrosine kinase that belongs to the insulin receptor family. LTK is mainly expressed in pre B cells and brain. Previously we cloned the full-length cDNA of human LTK, but no ligands have so far been identified, and hence, very little is known about the physiological role of LTK. To analyze the function of the LTK kinase, we constructed chimeric receptors composed of the extracellular domain of epidermal growth factor receptor and the transmembrane and the cytoplasmic domains of LTK and established cell lines that stably express these chimeric molecules. When cultured in medium containing EGF, growth of these cell lines was stimulated, and these fusion proteins became autophosphorylated and associated with Shc in vivo in a ligand-dependent manner. By treatment with EGF, Shc was associated with the Grb2/Ash-Sos complex. Our analyses demonstrate that LTK associates with Grb2/Ash through an internal adaptor, Shc, depending on a ligand stimulation. The LTK binding site for Shc was tyrosine 862 at the carboxyl-terminal domain and to a lesser extent tyrosine 485 at the juxtamembrane domain. Both of them are located in NP/AXY motif which is consistent with binding sites for Shc. These findings demonstrate that LTK can activate the Ras pathway in a ligand-dependent manner and that at least one of the functions of this kinase is involved in the cell growth.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Glibenclamide, a selective inhibitor of ATP-sensitive K+ channels, attenuates metabolic coronary vasodilatation induced by pacing tachycardia in dogs.

BACKGROUND: We previously reported that glibenclamide (a selective inhibitor of ATP-sensitive K+ channels [K+ATP channels]) inhibited metabolic coronary vasodilatation induced by beta 1-adrenoceptor stimulation. However, the role of K+ATP channels in metabolic coronary vasodilatation induced by tachycardia is still unknown. This study aimed to determine whether glibenclamide attenuates metabolic coronary vasodilatation induced by pacing-induced tachycardia. METHODS AND RESULTS: In anesthetized dogs, increasing heart rate from 103 +/- 1 to 160 beats per minute with atrial pacing increased coronary blood flow without altering arterial pressure and left ventricular pressure. Intracoronary infusion of glibenclamide at 1.5 and 5.0 micrograms.kg-1.min-1 did not alter basal coronary blood flow but significantly attenuated (P < .01) the tachycardia-induced coronary vasodilatation without altering the tachycardia-induced increase in myocardial oxygen consumption (MVO2). In conscious dogs, intracoronary glibenclamide at 5.0 micrograms.kg-1.min-1 attenuated (P < .05) coronary vasodilatation induced by ventricular pacing from 85 +/- 6 to 150 beats per minute. Glibenclamide markedly attenuated coronary vasodilation evoked with the K+ATP channel opener pinacidil. CONCLUSIONS: These data indicate that blockade of coronary vascular K+ATP channels with glibenclamide inhibited metabolic coronary vasodilatation induced by pacing tachycardia in dogs, suggesting that K+ATP channels are involved in the mechanism mediating metabolic coronary vasodilatation associated with pacing tachycardia.

Adenosine Triphosphate↗
PubMed1995

Properties of the voltage-gated calcium channels mediating dopamine and acetylcholine release from the isolated rat retina.

We examined the properties of voltage-gated calcium channels mediating endogenous dopamine (DA) and acetylcholine (ACh) release in the isolated rat retina. Application of 30 mM KCl elicited the release of DA and ACh, and these releases were abolished in Ca(2+)-free medium. The high K(+)-evoked DA release was largely blocked by both of omega-agatoxin IVA and omega-conotoxin MVIIC, P- and Q-type calcium channel antagonists, and partly blocked by isradipine, and L-type calcium channel antagonist, and omega-conotoxin GVIA, an N-type calcium channel antagonist. omega-Agatoxin IVA at a small dose, sufficient to block P-type channels alone, was however without effect. On the other hand, the high K(+)-evoked ACh release was partly blocked by omega-agatoxin IVA and omega-conotoxin MVIIC, but was resistant to isradipine and omega-conotoxin GVIA. Flunarizine, a non-selective T-type calcium channel antagonist, did not inhibit the release of DA and ACh. Cd2+ markedly blocked the release of both DA and ACh, Co2+ and Ni2+ slightly blocked the release of DA, and the release of ACh was not blocked by these two divalent cations. These results suggest that the high K(+)-evoked release of retinal DA is largely mediated by omega-agatoxin IVA and omega-conotoxin MVIIC sensitive calcium channels (probably Q-type channels), while the release of retinal ACh is largely mediated by as yet uncharacterized Cd2+ sensitive calcium channels. The properties of voltage-gated calcium channels involved in the release of ACh in the rat retina differ from those of DA.

Acetylcholine↗
PubMed1995

Fibroblast growth factor receptor is required for in vivo cardiac myocyte proliferation at early embryonic stages of heart development.

In birds and mammals, cardiac myocytes terminate mitotic activity in the neonatal period and regeneration of cardiac muscle does not occur after myocardial injury in adult hearts. Even embryonic myocytes, which actively proliferate in vivo, quickly lose mitotic activity when placed in cell culture. Several growth factors, including fibroblast growth factor (FGF), have been documented in embryonic hearts and some have been shown to influence myocyte terminal differentiation in culture. However, none of these growth factors have been shown to reactivate cell division in postmitotic myocytes nor have their in vivo functions been defined satisfactorily. To clarify the role of FGF signaling in heart growth, we prepared two retroviral vectors capable of suppressing (i) functions of FGF receptors (FGFRs) with a dominant-negative mutant of receptor type 1 (FGFR1) or (ii) the translation of endogenous FGFR1 by transcribing its antisense RNA. Both vectors inhibited myocyte proliferation and/or survival during the first week of chicken embryonic development but had much less effect after the second week. No apparent alteration of myocyte growth was observed after overexpression of full-length FGFR1. These results suggest that receptor-coupled FGF signaling regulates cardiac myocyte growth during tubular stages of cardiogenesis but that myocyte growth becomes FGF-independent after the second week of embryogenesis.

Animals↗
PubMed1995

Identification of the catalytic histidine residue participating in the charge-relay system of carboxypeptidase Y.

The essential histidine residue of carboxypeptidase Y (CPY) was modified by a site-specific reagent, a chloromethylketone derivative of benzyloxycarbonyl-L-phenylalanine. The single modified histidine residue was converted to N tau-carboxy-methyl histidine (cmHis) upon performic acid oxidation. A peptide containing cmHis was isolated from the tryptic-thermolytic digest. Based on the amino acid composition and sequence analysis, the peptide is shown to be Val-Phe-Asp-Gly-Gly-cmHis-MetO2-Val-Pro, which was derived from CPY cleaved by trypsin at Arg 391 and thermolysin at Phe 401, and thus His 397 was modified. This histidine residue has been implicated previously by X-ray analysis to participate in the charge-relay system of CPY.

Amino Acid Chloromethyl Ketones↗
PubMed1995

The relationship between HTLV-I-infected cell lines and uveitis.

BACKGROUND: Recently it has been revealed that human T-lymphotropic virus type I (HTLV-I) infection causes uveitis in human. We previously reported HTLV-I uveitis in a rabbit. To investigate the relationship between HTLV-I infection and uveitis, we established an HTLV-I-infected T-cell clone from the cells infiltrated in the anterior chamber of this rabbit and compared the viral production with that in other HTLV-I-infected cell lines. METHODS: The clonality was determined by Southern blot hybridization with various restriction enzymes. Flow-cytometric analysis was used for investigating the expression of cell surface antigens. To compare viral production, we performed reverse transcriptase assay of the culture media and inhibition enzyme-linked immunosorbent assay to determine the quantity of intracellular HTLV-I antigens. RESULTS: The established clone was Ia (MHC class II) positive T cell. This T-cell clone was able to produce about three times more HTLV-I antigens than other HTLV-I-infected cell lines tested. CONCLUSION: A T-cell clone established from anterior aqueous of an HTLV-I uveitis rabbit can produce more HTLV-1 antigen than other HTLV-I-infected cell lines tested and it can be recognized easily by the immune system. Therefore, this high virus production may have a causal relation to uveitis.

Animals↗
PubMed1995

Hypoxia-induced expression of vascular endothelial growth factor by retinal glial cells promotes in vitro angiogenesis.

To determine whether retinal glial cells (RGCs) participate in the paracrine regulation of retinal neovascularization, we investigated whether cultured RGCs synthesize and release vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) under normoxic or hypoxic conditions. Northern blot analysis demonstrated that cultured RGCs transcribed both VEGF mRNA with two molecular bands approximately 3.9 and 4.3 kilobases (kb), and bFGF mRNA with approximately 3.7 and 6.0 kb. The expression of VEGF mRNA was greatly enhanced by hypoxic cultivation (2% oxygen) when compared with normoxic cultivation (20% oxygen), while the expression of bFGF mRNA by RGCs was not significantly affected by hypoxia. The effects of RGCs-conditioned media (CM) on tritiated-thymidine incorporation and in vitro angiogenesis by retinal capillary endothelial cells (RECs) in producing the formation of capillary-like tubes in type I collagen gels, were evident in the observation that RGCs-CM harvested after hypoxic cultivation significantly enhanced tritiated-thymidine incorporation (1.9 times, P < 0.01) and in vitro angiogenesis (2.4 times, P < 0.01) compared with the normoxic RGCs-CM. These enhancing effects of RGCs-CM at hypoxia were suppressed by anti-VEGF neutralizing antibody. Furthermore, RECs were shown to express mRNA encoding the VEGF receptor flt-1 by northern blot analysis. These results suggest that VEGF expressed by RGCs under hypoxic conditions plays an integral role in the initiation and progression of retinal neovascularization in a paracrine manner.

Animals↗
PubMed1995

Significance of detection of enterovirus RNA in myocardial tissues by reverse transcription-polymerase chain reaction.

Enteroviruses are known to have association with human myocarditis and dilated cardiomyopathy (DCM). We screened biopsy specimens from patients with active myocarditis or DCM, and myocardial tissues from autopsy cases without cardiac diseases using polymerase chain reaction (PCR) gene amplification. Positive enteroviral signals were demonstrated from 4 of 5 patients with active myocarditis (80%), 7 of 42 patients with DCM(17%) and 3 of 27 autopsies (11%). Out of 7 PCR positive patients with DCM, 3 cases showed hypertrophy and disarray of cardiocytes, fibrosis in the interstitium, and a few inflammatory infiltrates. The remaining 4 cases with DCM and 3 PCR positive autopsy cases did riot exhibit histological findings compatible with those in myocarditis. Our results support the observations that enteroviruses are common aetiologic agents of myocarditis, and some cases of DCM. Our results also suggest the possibility that in some cases enteroviruses may persist in the myocardium without causing apparent pathological changes.

Adult↗