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Biomedical subjects

N Ueno

Publications and source records attributed to N Ueno.

At least 109 records · Page 6Linked to original sources
PubMed1998

Neuropeptide Y produces anxiety via Y2-type receptors.

In the present study, the effects of intracerebroventricular (ICV) NPY, [Leu31, Pro34]NPY and NPY13-36 have been evaluated with respect to anxiety in mice in the elevated plus maze. NPY had opposing effects on behavior, depending on the doses used. NPY decreased the normal preference for the closed arms of the maze at 0.7 nmol, indicating an anxiolytic effect; however, at 7 pmol NPY further increased the preference for the closed arm, indicating an anxiogenic effect. [Leu31, Pro34]NPY, a Y1-type receptor agonist, significantly reduced the preference for the closed arms at 70 pmol. NPY13-36, a Y2-type receptor agonist, significantly intensified the preference at 20 pmol. It has been demonstrated that NPY produces not only an anxiolytic effect via Y1-type receptors, but also an anxiogenic effect via Y2-type receptors. The time course of these NPY actions are quite different and the anxiogenic effect was observed only shortly after ICV NPY injection.

Animals↗
PubMed1998

Motilin increases food intake in mice.

The effect of motilin on food intake was investigated in nonfood-deprived mice. A significant increase in food intake was observed 1 h after ICV administration of motilin (3 nmol/mouse) and continued for 2 h. This effect was attenuated markedly by the motilin receptor antagonist GM-109 (0.3-3 nmol/mouse) in a dose-related manner. GM-109 alone had no effect on food intake. These results indicate that motilin receptors are present in the brain and may have a role in the regulation of food intake.

Animals↗
PubMed1998

Anxiolytic effect of motilin and reversal with GM-109, a motilin antagonist, in mice.

There have been few reports on the effects of the brain-gut peptide motilin on the central nervous system (CNS). We administered motilin intracerebroventricularly to mice and investigated the effect of motilin on anxiety using an elevated plus-maze. Motilin produced a significant decrease in anxiety with an inverted U-shaped dose response. To determine whether the anxiolytic effect of motilin was mediated via motilin receptors in the brain, the effect of GM-109, a novel motilin receptor antagonist, was investigated. GM-109 showed a significant and dose-dependent antagonism on the motilin-induced anxiolytic effect. GM-109 administered alone had no effect on anxiety. These results suggest that motilin receptors are present in the brain and may have a role in anxiety and emotion.

Animals↗
PubMed1998

BRAM1, a BMP receptor-associated molecule involved in BMP signalling.

BACKGROUND: TGF-beta superfamily members elicit signals through the stimulation of serine/threonine-kinase receptors. Recently, molecules associated with several TGF-beta family receptors have been cloned. One such molecule, the immunophilin FKBP12, has been reported to interact with TGF-beta family type I receptors. However, the identity of signalling specific molecules interacting with the receptor was unknown. RESULTS: To clarify the factors mediating bone morphogenetic protein (BMP) receptor signalling, a cytoplasmic molecule associated with the BMP type IA receptor (BMPR-IA) was isolated using the yeast two-hybrid system. We designated the molecule BMP receptor associated molecule 1 (BRAM1). BRAM1 is an alternatively spliced form of BS69, a factor previously identified as an adenovirus E1A-associated protein. BRAM1 was localized to the cytoplasmic region in mammalian cells, whereas BS69 is localized to the nucleus. BRAM1 bound specifically to BMPR-IA in mammalian cells. The C-terminal half of BRAM1 was found to be sufficient for binding to BMPR-IA. CONCLUSIONS: BRAM1, a BMPR-IA associated molecule, was isolated using the yeast two-hybrid system, and found to associate specifically with BMPR-IA. BRAM1 may thus serve as an interacting protein in the BMP signal pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1998

A pilot study on modified endoscopic variceal ligation using endoscopic ultrasonography with color Doppler function.

OBJECTIVE: The purpose of the study was to evaluate feasibility of modified endoscopic variceal ligation (EVL), namely the "intensive ligation" method, using endoscopic ultrasonography with color Doppler function (EUS-CD). METHODS: Forty-five patients with esophageal varices were treated by modified EVL. Variceal hemodynamics in 38 patients were examined using EUS-CD, which showed abdominal hemodynamics in detail under physiological conditions before and after the modified procedure. RESULTS: 1) The median number of treatment sessions was 3.2, and 41 O-rings on average were required per individual patient. 2) The median nonrecurrence period after treatment was 18 months (Kaplan-Meier method). 3) Nine patients with a good response to modified EVL did not have recurrences for 16.9+/-2.8 months, and five with a poor response had recurrences at 5.8+/-2.2 months. Gastric varices were related to the response to modified EVL (p < 0.05, Mann-Whitney's U test). 4) Minor complications in modified EVL as well as standard EVL were experienced; however, we had a patient with the development of meningitis, which was a major septic complication. 5) Before modified EVL, EUS-CD demonstrated that good responders had undeveloped (grade I) gastric varices in five of nine (56%); however, poor responders had developed (grade III) gastric varices in four of five (80%) (p < 0.05, Mann-Whitney's U test]. 6) After modified EVL, EUS-CD revealed that six of nine (67%) good responders and one of five (20%) poor responders showed a decrease in color signals in supplying veins; however, none of the former (0%) and three of the latter (60%) showed an increase (p < 0.05, Mann-Whitney's U test]. CONCLUSION: Modified EVL was safe and effective, at least with regard to intermediate-term outcome, especially when treating patients with undeveloped gastric varices revealed by EUS-CD. Both good and poor responders showed no exacerbation of gastric varices after the modified procedure, ultrasonographically as well as endoscopically.

Adult↗
PubMed1998

Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.

PURPOSE: To investigate the use of a nonmyeloablative fludarabine-based preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-leukemia/lymphoma (GVL) as the primary treatment modality for patients with chronic lymphocytic leukemia (CLL) and lymphoma. PATIENTS AND METHODS: Fifteen patients were studied. Six patients were in advanced refractory relapse, and induction therapy had failed in two patients. Patients with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/m2 and cyclophosphamide 900 to 2,000 mg/m2. Patients with intermediate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m2 daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m2 daily for 2 days. Chemotherapy was followed by allogeneic stem-cell infusion from HLA-identical siblings. Patients with residual malignant cells or mixed chimerism could receive a donor lymphocyte infusion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 months posttransplantation if graft-versus-host disease (GVHD) was not present. RESULTS: Eleven patients had engraftment of donor cells, and the remaining four patients promptly recovered autologous hematopoiesis. Eight of 11 patients achieved a complete response (CR). Five of six patients (83.3%) with chemosensitive disease continue to be alive compared with two of nine patients (22.2%) who had refractory or untested disease at the time of study entry (P = .04). CONCLUSION: These findings indicate the feasibility of allogeneic hematopoietic transplantation with a nonablative preparative regimen to produce engraftment and GVL against lymphoid malignancies. The ability to induce remissions with donor lymphocyte infusion in patients with CLL, Richter's, and low-grade and intermediate-grade lymphoma is direct evidence of GVL activity against these diseases. This approach appears to be most promising in patients with chemotherapy-responsive disease and low tumor burden.

Aged↗
PubMed1998

Role of dpp signalling in prepattern formation of the dorsocentral mechanosensory organ in Drosophila melanogaster.

A proneural cluster of dorsocentral bristles forms adjacent to the dorsal side of wg-expressing cells in the notum region of the wing imaginal disc. It has been shown that wg activity is required for these structures to form. However, the restriction of this proneural cluster to the dorsal posterior side of the wg expression domain in the anterior compartment of the wing imaginal disc has suggested that Wg signalling itself is insufficient to establish the dorsocentral proneural cluster. Some factor(s) from the posterior side must participate in this action in cooperation with Wg signalling. We have examined the role of Dpp signalling in dorsocentral bristle formation by either ectopically activating or conditionally reducing Dpp signalling. Ubiquitous activation of Dpp signalling in the notum region of the wing imaginal disc induced additional dorsocentral proneural cluster all along the dorsal side of the wg expression domain, and altered wg expression. Conditional loss-of-function of Dpp signalling during disc development resulted in the inhibition of dorsocentral proneural cluster formation and expansion of the wg expression domain. These results suggest that Dpp signalling has two indispensable roles in dorsocentral bristle formation: induction of the dorsocentral proneural cluster in cooperation with Wg signalling and restriction of the wg expression domain in the notum region of the wing imaginal disc.

Activin Receptors↗
PubMed1998

Thermostable neutral protease resembling thermolysin derived from Bacillus brevis MIB001.

A microbe producing a protease with strong thermostability that was released extracellularly was isolated from soil. The isolate, MIB001, grew at from 15 to 51 degrees C and pH 5.1-8.8 and was tentatively identified as a strain of Bacillus brevis. Rabbit antisera raised against a pure preparation of the protease did not cross-react with thermolysin or neutral metalloprotease from Bacillus stearothermophilus KP1236.

Amino Acid Sequence↗
PubMed1998

[Differential diagnosis of pancreatic tumor by contrast enhanced color Doppler ultrasonography].

For evaluating abdominal hemodynamic changes and diagnosing mass lesion, recently color Doppler ultrasonography (CDUS) have been applied. However, there are limitations in visualizing Doppler signals in small vessels with low flow velocity. To overcome these shortcomings, several contrast agents that facilitate evaluation of abdominal hemodynamics have been developed. We underwent Contrast enhanced color Doppler ultrasonography (CECD) with a galactose-based contrast agent in three patients with pancreatic tumor. In the patient with tumor forming pancreatitis, only CECD visualized the color signal in and around the tumor. In the patient with duct cell cancer, CDUS and CECD visualized only the color signal of the splenic artery penetrating the tumor, whereas in the patient with islet cell tumor, CECD visualized numerous color signals in the tumor. CECD appears to be useful in diagnosing pancreatic tumor.

Adult↗
PubMed1998

[Priapism treated by caverno-glandular shunt, caverno-saphenous shunt and caverno-spongiosum shunt: report of a case].

A 44-year-old man visited a local urologist complaining of continuous pain and tumescence at penis persisting for 3 days. He was diagnosed with priapism. A caverno-glandular and caverno-saphenous shunt was performed. He presented to our hospital 3 days later, because the symptoms especially tumescence continued. We confirmed the diagnosis of low-flow priapism from cavernosography and intracavenal blood-gasometry and performed caverno-spongiosum shunt. Detumescence was finally achieved after the operation.

Adult↗
PubMed1998

[A sporadic case of episodic ataxia with nystagmus (EA-2)].

A 39-year-old man with episodic ataxia with nystagmus (EA-2) was reported. He showed intermittent cerebellar dysfunction, i.e., ataxia, nystagmus, dysarthria and vertigo, since he was 10 years old. Although this attack lasted for several hours, he was normal with exception of interictal nystagmus. His parents and sister showed no episodic ataxia. We ruled out the diseases, which may cause episodic ataxia, such as multiple sclerosis, vascular disorders, metabolic disorders and congenital anomalies. He was released from the attack by treatment with acetazolamide. EA-2 has been associated with mutations in the alpha 1A-voltage dependent calcium channel gene (CACNL1A4), which is also affected in familial hemiplegic migraine (FMH) and spinocerebellar ataxia type 6 (SCA6). In EA-2, frame-shift mutation leading to premature stop and splice-site mutation leading to truncated, non-functional channel protein have been reported. However, our patient did not have the mutations in the CACNL1A4 gene that were previously reported. In addition, our patient did not have an expanded CAG allele in the CACNL1A4 gene which is responsible for SCA6. Further examination is required to address whether a new mutation exists in the CACNL1A4 gene in our patient.

Acetazolamide↗
PubMed1997

High-frequency generation of transgenic zebrafish which reliably express GFP in whole muscles or the whole body by using promoters of zebrafish origin.

Despite a number of reports on transgenic zebrafish, there have been no reports on transgenic zebrafish in which the gene is under the control of a promoter of zebrafish origin. Neither have there been reports on transgenic zebrafish in which the gene is under the control of a tissue-specific promoter/enhancer. To investigate whether it is possible to generate transgenic zebrafish which reliably express a reporter gene in specific tissues, we have isolated a zebrafish muscle-specific actin (alpha-actin) promoter and generated transgenic zebrafish in which the green fluorescent protein (GFP) reporter gene was driven by this promoter. In total, 41 GFP-expressing transgenic lines were generated with a frequency of as high as 21% (41 of 194), and GFP was specifically expressed throughout muscle cells in virtually all of the lines (40 of 41). Nonexpressing transgenic lines were rare. This demonstrates that a tissue-specific promoter can reliably drive reporter gene expression in transgenic zebrafish in a manner identical to the control of the endogeneous expression of the gene. Levels of GFP expression varied greatly from line to line; i.e., fluorescence was very weak in some lines, while it was extremely high in others. We also isolated a zebrafish cytoskeletal beta-actin promoter and generated transgenic zebrafish using a beta-actin-GFP construct. In all of the four lines generated, GFP was expressed throughout the body like the beta-actin gene, demonstrating that consistent expression could also be achieved in this case. In the present study, we also examined the effects of factors which potentially affect the transgenic frequency or expression levels. The following results were obtained: (i) expression levels of GFP in the injected embryo were not strongly correlated to transgenic frequency; (ii) the effect of the NLS peptide (SV40 T antigen nuclear localization sequence), which has been suggested to facilitate the transfer of a transgene into embryonic nuclei, remained to be elusive; (iii) a plasmid vector sequence placed upstream of the construct might reduce the expression levels of the reporter gene.

Actins↗
PubMed1997

Constitutively active BMP type I receptors transduce BMP-2 signals without the ligand in C2C12 myoblasts.

Bone morphogenetic protein-2 (BMP-2), a member of transforming growth factor-beta superfamily, inhibits the terminal differentiation of C2C12 myoblasts and changes their differentiation pathway into cells expressing osteoblast phenotypes such as alkaline phosphatase (ALP) activity and osteocalcin production (Katagiri et al., 1994, J. Cell Biol. 127, 1755-1766). Two type I receptors for BMP-2 (BMPR-IA and BMPR-IB) have been cloned, but the role of the respective receptors in signal transduction is not clear. In the present study, we examined the signal transduction of BMP-2 in C2C12 cells using constitutively activated mutant BMPR-IA and BMPR-IB. C2C12 cells expressed BMPR-IA and BMPR-II mRNAs, but not BMPR-IB mRNA at detectable levels in Northern blotting. When mutated BMPR-IA and BMPR-IB were transiently transfected into C2C12 cells, both BMPR-IA and BMPR-IB similarly induced ALP activity in the absence of BMP-2. We also established subclonal cell lines of C2C12 cells by stably transfecting mutated BMPR-IB. When the mutated BMPR-IB-transfected cells were cultured in medium with low serum (differentiation medium) without BMP-2, the cells differentiated into ALP-positive mononuclear cells and not into myosin heavy chain-positive myotubes. These mutated BMPR-IB-transfected cells expressed ALP activity and osteocalcin mRNA in a time-dependent manner, but neither muscle creatine kinase nor myogenin mRNAs. These results indicate that the mutated BMP-2 type I receptors can constitutively transduce BMP-2 signals in the absence of the ligand in C2C12 cells.

Alkaline Phosphatase↗
PubMed1997

Regulation of epidermal induction by BMP2 and BMP7 signaling.

The specification of neural fate in Xenopus embryos has been shown to be under regulation by negative factors. The secreted protein bone morphogenetic protein-4 (BMP4) has been identified as one of these factors: in the early gastrula ectoderm, BMP4 can both inhibit neural fate and induce epidermis. In this study, we show that two other Xenopus BMP genes, BMP2 and BMP7, are endowed with the same types of activities. First, we show that expression of a dominant negative form of the BMP2 ligand, which blocks normal processing of the wild-type ligand, causes neuralization of Xenopus ectoderm. Second, we have isolated the Xenopus BMP2/7 receptor (XALK2) and generated a constitutively active mutant that signals in a ligand-independent manner. We show that signals from the activated BMP2/7 receptor also inhibit neuralization and induce epidermis in dissociated ectoderm cells. Consistent with both findings we show that secreted BMP2 and BMP7 ligands can also mediate neural inhibition and epidermal induction. These results suggest that both BMP2 and BMP7 may be involved independently or together with BMP4 in the inhibition of the neural fate and the onset of the epidermal induction pathway in vivo. This further supports the idea that epidermal induction is due to the effects of multiple signals from heterogeneous BMP genes.

Animals↗
PubMed1997

A kinase domain-truncated type I receptor blocks bone morphogenetic protein-2-induced signal transduction in C2C12 myoblasts.

Members of the transforming growth factor (TGF)-beta superfamily bind the transmembrane serine/threonine kinase complex consisting of type I and type II receptors. Their intracellular signals are propagated via respective type I receptors. Bone morphogenetic protein (BMP)-2, a member of the TGF-beta superfamily, induces ectopic bone formation when implanted into muscular tissues. Two type I receptors (BMPR-IA and BMPR-IB) have been identified for BMP-2. We have reported that BMP-2 inhibits the terminal differentiation of C2C12 myoblasts and converts their differentiation pathway into that of osteoblast lineage cells (Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E., Takahashi, N., Ikeda, T., Rosen, V., Wozney, J. M., Fujisawa-Sehara, A. and Suda, T. (1994) J. Cell Biol. 127, 1755-1766). In the present study, we examined the involvement of functional BMP-2 type I receptors in signal transduction in C2C12 cells, which expressed mRNA for BMPR-IA, but not for BMPR-IB in Northern blotting. TGF-beta type I receptor (TbetaR-I) mRNA was also expressed in C2C12 cells. Subclonal cell lines of C2C12 that stably expressed a kinase domain-truncated BMPR-IA (DeltaBMPR-IA) differentiated into myosin heavy chain-expressing myotubes but not into alkaline phosphatase (ALP)-positive cells, even in the presence of BMP-2. In contrast, the differentiation of the DeltaBMPR-IA-transfected C2C12 cells into myotubes was suppressed by TGF-beta1, as in the parental C2C12 cells. BMP-2 did not efficiently suppress the mRNA expression of muscle-specific genes such as muscle creatine kinase, MyoD, and myogenin, nor did it induce the expression of ALP mRNA in the DeltaBMPR-IA-transfected C2C12 cells. In contrast, TGF-beta1 inhibited mRNA expression of the muscle-specific genes in those cells. When wild-type BMPR-IA was transiently transfected into the DeltaBMPR-IA-transfected C2C12 cells, a number of ALP-positive cells appeared in the presence of BMP-2. Transfection of wild-type BMPR-IB or TbetaR-I failed to increase the number of ALP-positive cells. These results suggest that the BMP-2-induced signals, which inhibit myogenic differentiation and induce osteoblast differentiation, are transduced via BMPR-IA in C2C12 myoblasts.

Affinity Labels↗
PubMed1997

Development of flexible ventriculoscope (Yamadori-type VII) and its application to experimental animals.

We developed a new ventriculoscope (Yamadori-type VII), a 2.1 mm calibrated fiberscope with a monopolar coagulator, that can be inserted from the cisterna cerebellomedullaris into the third cerebral ventricle of experimental animals, like dogs. With the improved performance of the neuroendoscope compared to its prototype, Yamadori III, it was possible to inspect clearly and to produce electrocoagulative lesions accurately on any part of the intraventricular structures with minimal injury to nearby vital brain areas.

Animals↗