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Biomedical subjects

N Ueno

Publications and source records attributed to N Ueno.

At least 145 records · Page 8Linked to original sources
PubMed1997

Effects of swimming training on brown-adipose-tissue activity in obese ob/ob mice: GDP binding and UCP m-RNA expression.

Brown adipose tissue (BAT) of obese animals is generally in a relatively atrophied and thermogenically quiescent state. The aim of the current study was to investigate the effect of swimming training on BAT activity in lean and obese (ob/ob) mice. The trained mice underwent a 6-week endurance swimming training (1 h/day, 5 days/week) in water at 35-36 degrees C. The swimming training significantly increased BAT mass and its protein content in both the lean and obese mice, suggesting hypertrophy. After swimming training, the amounts of protein and guanosine 5'-diphosphate binding in the mitochondria recovered from BAT of both mice increased significantly as compared with the respective sedentary groups, whereas the uncoupling protein (UCP) content increased significantly only in lean mice. After swimming training, the level of UCP mRNA expression did not change substantially in lean mice but appeared to increase in obese mice. The results obtained here suggest that swimming training leads to an increase in the nonshivering thermogenesis of obese mice in addition to lean mice.

Adipose Tissue, Brown↗
PubMed1996

The role of BMP-4 and GATA-2 in the induction and differentiation of hematopoietic mesoderm in Xenopus laevis.

Vertebrate embryonic blood formation is regulated by factors that participate in dorsal-ventral patterning and mesoderm induction. The GATA-binding transcription factors are required for normal hematopoiesis and are expressed during gastrulation when ventral mesoderm (VM) is induced to form blood. Based on the recent demonstration that bone morphogenetic protein (BMP-4) is a potent ventralizing factor and inducer of hematopoietic tissue, we hypothesized that GATA-2 could be induced or activated by BMP-4. Here we demonstrate that BMP-4 can stimulate GATA-2 expression, and that expression of a dominant negative BMP-4 receptor can suppress GATA-2 induction by BMP-4 in ventral mesoderm. Over-expression of GATA-2 in ventral mesoderm leads to increased globin production and forced expression of GATA-2 in primitive ectoderm adjacent to ventral mesoderm also stimulates globin expression. Our results suggest that BMP-4 and GATA-2 can function in two adjacent germ layers, mesoderm and ectoderm, to participate in blood cell formation during embryogenesis.

Animals↗
PubMed1996

TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction.

Transforming growth factor-beta (TGF-beta) regulates many aspects of cellular function. A member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family, TAK1, was previously identified as a mediator in the signaling pathway of TGF-beta superfamily members. The yeast two-hybrid system has now revealed two human proteins, termed TAB1 and TAB2 (for TAK1 binding protein), that interact with TAK1. TAB1 and TAK1 were co-immunoprecipitated from mammalian cells. Overproduction of TAB1 enhanced activity of the plasminogen activator inhibitor 1 gene promoter, which is regulated by TGF-beta, and increased the kinase activity of TAK1. TAB1 may function as an activator of the TAK1 MAPKKK in TGF-beta signal transduction.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Involvement of Ras/Raf/AP-1 in BMP-4 signaling during Xenopus embryonic development.

Previously, we elucidated the role of bone morphogenetic protein 4 (BMP-4) in the dorsal-ventral patterning of the Xenopus embryo by using a dominant negative mutant of the BMP-4 receptor (DN-BR). The present paper describes the involvement of Ras, Raf, and activator protein 1 (AP-1) in BMP-4 signaling during Xenopus embryonic development. The AP-1 activity was determined by injecting an AP-1-dependent luciferase reporter gene into two-cell-stage Xenopus embryos and measuring the luciferase activity at various developmental stages. We found that injection of BMP-4 mRNA increased AP-1 activity, whereas injection of DN-BR mRNA inhibited AP-1 activity. Similar inhibitory effects were seen with injection of mRNAs encoding dominant negative mutants of c-Ha-Ras, c-Raf, or c-Jun. These results suggest that the endogenous AP-1 activity is regulated by BMP-4/Ras/Raf/Jun signals. We next investigated the effects of Ras/Raf/AP-1 signals on the biological functions of BMP-4. DN-BR-induced dorsalization of the embryo, revealed by the formation of a secondary body axis or dorsalization of the ventral mesoderm explant analyzed by histological and molecular criteria, was significantly reversed by coinjection of [Val12]Ha-Ras, c-Raf, or c-Jun mRNA. Furthermore, the BMP-4-stimulated erythroid differentiation in the ventral mesoderm was substantially inhibited by coinjection with the dominant negative c-Ha-Ras, c-Raf, or c-Jun mutant. Our results suggest the involvement of Ras/Raf/AP-1 in the BMP-4 signaling pathway.

Animals↗
PubMed1996

Cloning of rat type I receptor cDNA for bone morphogenetic protein-2 and bone morphogenetic protein-4, and the localization compared with that of the ligands.

A rat homologue cDNA of mouse (Koenig et al. [1994] Mol. Cell Biol. 14:5961-5974; Suzuki et al. [1994] Proc. Natl. Acad. Sci. USA 91: 10255-10259) and human (ten Dijke et al. [1994] J. Biol. Chem. 269:16985-16988) type I receptors for BMP-2 and BMP-4 was cloned. Tissue distribution of the receptor mRNA was studied by in situ hybridization using rats at embryonic days 9, 13, 15, and 18 as well as 1- and 5-day-old postnatal rats. In the rats at embryonic days 9, 13, and 15, the receptor mRNA was diffusely expressed over the embryonic bodies. At embryonic day 18, the receptor mRNA expression was high in the hair and whisker follicles, tooth bud, cartilage, bone, digestive organs, lung, kidney, heart, and meninges. The receptor mRNA was expressed over a much wider area than those of the ligands in many organs. In the lung and digestive organs, the receptor mRNA was diffusely expressed and most highly expressed in the bronchial epithelium and muscle layer, respectively, in both of which mRNA expression of the ligands was undetectable. The receptor mRNA was highly expressed in the meninges, although neither of the ligands was expressed in or near this region. These results suggest that this receptor participates in both mesoderm formation in early embryogenesis and differentiation of mesodermal cells during maturation of organs, and further suggest the presence of another factor(s) that binds the type I receptor.

Amino Acid Sequence↗
PubMed1996

Evidence of cross-link formation of vitreous collagen during experimental ocular inflammation.

PURPOSE: To determine the mechanisms of vitreous changes during ocular inflammation. METHODS: We investigated vitreous changes, with special emphasis on collagen, in an experimental model of ocular inflammation induced by intravitreal injection of endotoxin (Escherichia coli) in rabbits. RESULTS: Inflammation caused gel contraction and loss of elasticity, accompanied by release of a water-like liquid from the gel, and increases in the amount of insoluble material and high-molecular-weight components of vitreous collagen, presumably due to extensive cross-links of the collagen molecules. Those changes were partially inhibited by intravitreal injection of superoxide dismutase. CONCLUSIONS: The cross-links of vitreous collagen may promote vitreous gel contraction and release of a water-like liquid from the gel. Superoxide anion may play a role in this process.

Animals↗
PubMed1996

Pancreatic arteriovenous malformation with duodenal ulcer. Demonstration by color Doppler ultrasonography.

We report the color Doppler ultrasonography features of arteriovenous malformation (AVM) of the pancreas, a very rare disease. The patient was a 52-year-old man with congenital AVM of the pancreas and a duodenal ulcer that had been resistant to medication. Endoscopic color Doppler ultrasonography (color Doppler EUS) revealed many abnormal color signals showing pulsatile wave form at the portion of the duodenal wall involving the duodenal ulcer. Extracorporeal color Doppler ultrasonography revealed a mosaic-like color signal, caused by turbulent flow, in the portal trunk. Angiography demonstrated a vascular network with extensive proliferation at the pancreatic head and early portal filling. It is possible that the pancreatic AVM had caused the duodenal ulcer. Color Doppler EUS can be a useful modality for detection of vessel abnormalities of the gastrointestinal tract.

Arteriovenous Malformations↗
PubMed1996

EM523L, a nonpeptide motilin agonist, stimulates gastric emptying and pancreatic polypeptide secretion.

We investigated the efficacy and the mechanism of action of EM523L, a nonpeptide motilin agonist (motilide), on the stimulation of gastric emptying and on the release of gut peptides after ingestion of a solid meat in normal controls (n = 8) and in diabetic patients (n = 8) with signs of neuropathy. A dose of 2 mg EM523L was administered IV over 15 min just after ingestion of a solid meal (200 kcal Gastric emptying was measured by a radionuclide technique. EM523L accelerated gastric emptying and markedly augmented postprandial pancreatic polypeptide (PP) response in both normal control and diabetic patients. This may suggest the mediation of the Vagal-cholinergic pathway to accelerate gastric emptying. The present study offers a promising therapeutic potential of the motilide in gastrointestinal motility disorders like those observed in diabetics mellitus.

Adult↗
PubMed1996

An ascidian homologue of vertebrate BMPs-5-8 is expressed in the midline of the anterior neuroectoderm and in the midline of the ventral epidermis of the embryo.

The ascidian tadpole larva is thought to be the prototype for the ancestral chordate. Although ascidians show a highly determinate mode of development, recent studies suggest significant roles of cell-cell interaction during embryogenesis. To elucidate the signaling molecules responsible for the cellular interaction, we investigated an ascidian homologue of the transforming growth factor beta (TGF-beta) superfamily. HrBMPa is an ascidian member of the 60A subclass of the BMP subfamily. Molecular phylogenetic analysis suggested that HrBMPa branched prior to further divergence of vertebrate BMPs-5-8. The zygotic expression of HrBMPa was initiated around gastrulation. HrBMPa transcripts were first evident in precursor cells of the spinal cord, notochord, epidermis and nervous system, although signals in the first two regions quickly disappeared. In neurulae and early tailbud embryos, transcripts were evident in the adhesive organ, midline of the anterior dorsal neuroectoderm and midline of both ventral and dorsal ectoderm, suggesting that HrBMPa plays a major role in neuroectodermal cell differentiation during embryogenesis. This HrBMPa expression profile resembled that of Xenopus BMP-7, implying a primordial function of BMP-7 among vertebrate BMPs-5-8.

Amino Acid Sequence↗
PubMed1996

Assessment of the course and variations of the hepatic artery in bile duct cancer by intraductal ultrasonography.

BACKGROUND: We evaluated the course and variations of the hepatic artery in bile duct cancer using intraductal ultrasonography (IDUS). METHODS: IDUS was used to demonstrate the course of the hepatic artery preoperatively in 20 patients with extrahepatic bile duct cancer, and the image was compared with angiographic and surgical findings. RESULTS: IDUS was able to assess tumor invasion to the main branch of the right hepatic artery in all cases. However, it demonstrated only three cases in the left hepatic artery and four cases in the proper hepatic artery. When the hepatic artery indicated re-entry or bifurcation on the IDUS image, the proximal portion of re-entry or bifurcation was established as the proper hepatic artery, but when it showed neither re-entry nor bifurcation it was established as the right hepatic artery. CONCLUSIONS: IDUS demonstrated the main branch of the right hepatic artery in all cases, but was not useful for demonstration of the left and proper hepatic arteries. Correct assessment of re-entry and bifurcation was essential on IDUS images for making the distinction between the right hepatic artery and the proper hepatic artery.

Aged↗
PubMed1996

Laparoscopic transcystic cholangioscopic lithotripsy for common bile duct stones during laparoscopic cholecystectomy.

BACKGROUND AND STUDY AIMS: Following the recent introduction of laparoscopic cholecystectomy (LC) for cholecystolithiasis, treatment of concomitant common bile duct (CBD) stones has been evaluated by using laparoscopic choledochotomy, a transcystic approach, or by means of endoscopic sphincterotomy (ES) before or after LC. PATIENTS AND METHODS: During laparoscopic cholecystectomy, we attempted lithotripsy of CBD stones using laparoscopic transcystic cholangioscopy with lithotripsy (LTCL), in 70 patients out of 950 laparoscopic cholecystectomies. Preparatory tests included laboratory values, ultrasound, and performance of endoscopic retrograde cholangiography (ERC) with placement of a nasobillary tube (without sphincterotomy). RESULTS: Introduction of the cholangioscope into the CBD was successful in 65 patients (92.9%) and CBD clearance was completely achieved by LTCL alone in 51 (78.5%). The overall success rate was therefore 73%. The remaining 19 cases required postoperative procedures such as extracorporeal shock-wave lithotripsy without ERC or ES (successful in all). The average hospital stay period was 9.4 days for patients in whom CBD clearance was achieved by LTCL alone. This period did not differ significantly from that of patients who underwent LC alone (8.4) days. The operation time was about 70 minutes longer for the LTCL group (total time 174 minutes on average) than for the LC group (107 minutes). We did not observe any series complications during or after LTCL (mean follow-up period: 34 months). CONCLUSION: LTCL in combination with LC allows shortening of the hospital stay and a swift return to work for patients with CBD stones. This procedure also preserves the function of the sphincter of Oddi, so that the longterm prognosis for patients is likely to be very good.

Adult↗
PubMed1996

Assessment of pancreatic parenchymal invasion by bile duct cancer using intraductal ultrasonography.

BACKGROUND AND STUDY AIMS: This study was performed to clarify the diagnostic accuracy of intraductal ultrasonography (IDUS) in assessing pancreatic parenchymal invasion by bile duct cancer. PATIENTS AND METHODS: Preoperative assessment of pancreatic parenchymal invasion was carried out by IDUS via a percutaneous tract or a transpapillary route in 18 patients with extrahepatic bile duct cancer. Various probes with diameters of 1.4, 2.0, 2.4, 2.6 and 3.2 mm, and frequencies of 7.5, 15, 20 and 30 MHz were used. All patients underwent angiography and endoscopic ultrasonography (EUS). In the first six cases, IDUS and EUS images were analyzed retrospectively without knowledge of the operative outcome or the results of other imaging tests. In the subsequent 12 cases, the IDUS und EUS images were prospectively reviewed prior to surgery. The diagnostic accuracy of IDUS was compared with angiography and EUS by means of a histopathological examination of the resected specimens. RESULTS: The accuracy of IDUS, EUS, and angiography in assessing pancreatic parenchymal invasion was 100%, 78% and 61%, respectively. However, IDUS could not assess pancreatic capsular invasion. The accuracy of IDUS in assessing horizontal tumor extension to the intrapancreatic bile duct and to the hepatic side was 83% and 72%, respectively. CONCLUSIONS: IDUS proved useful for assessing the extension of cancer invasion to the pancreatic parenchyma, but not to the pancreatic capsule or mucosal surface.

Aged↗
PubMed1996

BMP-4 mediates interacting signals between the neural tube and skin along the dorsal midline.

BACKGROUND: The neural tube and its overlying tissues (skin and mesenchyme) interact along the dorsal midline during early development. This has been previously demonstrated experimentally in chicken embryos by the fact that the dorsal neural tube transplanted ectopically induced expression of Msx 2 in the adjacent tissues. It is important to identify the molecules responsible for these interactions. RESULTS: We observed that BMP-4, a member of the TGFbeta-family, is expressed in the dorsal neural tube in a pattern closely correlated with that of Msx 2. In order to investigate whether BMP-4 mediates the signal between the neural tube and the skin/mesenchyme, BMP-4 was ectopically administered in ovo either by implantation of the recombinant protein or transplantation of COS cells producing BMP-4. Both manipulations resulted in ectopic induction of Msx 2 expression in the adjacent skin/mesenchyme. In addition, the activity of BMP-4 in inducing Msx 2 was counteracted by the floor plate. CONCLUSION: These data suggest that BMP-4 positively mediates the signals from the neural tube to the adjacent tissues and that this signal may be an essential step for the establishment of the dorsal midline structures.

Bone Morphogenetic Protein 4↗
PubMed1996

NE-induced contraction, alpha 1-adrenergic receptors, and Ins(1,4,5)P3 responses in cerebral arteries.

Adrenergic-mediated responses in cerebral vessels in vitro differ with vessel segment. We performed this study to test the hypothesis that these vessel-specific cerebral artery norepinephrine (NE)-induced contractility changes are mediated in part by differences in alpha 1-adrenergic receptor (alpha 1-R) density (Bmax) or antagonist dissociation constant (KD), and/or inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] synthesis. In common carotid (Com), circle of Willis (Wil), and middle cerebral arteries (MCA) from adult sheep we measured NE-induced contractions. We also quantified alpha 1-R in these, and in anterior, middle, and posterior (AMP) cerebral arteries and cerebral microvessels (Micro). In addition, we quantified NE-induced Ins(1,4,5)P3 synthesis. pD2 values of Com and MCA were 5.2 +/- 0.1 and 6.3 +/- 0.1, respectively. In contrast, the MCA maximum response to NE compared with K+ was much lower than that of the Com. In the Com, Wil, AMP, and Micro, alpha 1-R Bmax was 54 +/- 3, < 5 +/- 2, 23 +/- 3, and 35 +/- 3 fmol/mg protein, respectively. KD averaged 0.20 +/- 0.05 nM in the several vessel groups. In Com and in AMP cerebral arteries, NE produced a rapid increase in Ins(1,4,5)P3 with a peak at 45 s, and 50% effective concentration of 5.5 +/- 0.2 microM. NE stimulated a 240% increase of Ins(1,4,5)P3 in both Com and AMP, whereas Wil showed essentially no response. The ovine MCA was more sensitive to NE than was the Com. In contrast, MCA showed a much lower maximum contractile response to NE compared with K+. Cerebral arteries (AMP) had only about half the alpha 1-R density of the Com. In AMP cerebral arteries, both the basal and NE-stimulated Ins(1,4,5)P3 values were much less than those of the Com. In MCA, the ratio of Ins(1,4,5)P3 response to alpha 1-R Bmax was much greater than in Com. These findings suggest important artery-to-artery differences in components of the cerebrovascular alpha 1-R-mediated contractile pathway. They also suggest considerable potential for modulation of pharmacomechanical coupling and homeostatic regulation of cerebrovascular tone.

Animals↗