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Biomedical subjects

N Ueno

Publications and source records attributed to N Ueno.

At least 91 records · Page 5Linked to original sources
PubMed1999

Dual specificity of activin type II receptor ActRIIb in dorso-ventral patterning during zebrafish embryogenesis.

Members of the transforming growth factor-beta (TGF-beta) superfamily are thought to regulate specification of a variety of tissue types in early embryogenesis. These effects are mediated through a cell surface receptor complex, consisting of two classes of ser/thr kinase receptor, type I and type II. In the present study, cDNA encoding zebrafish activin type II receptors, ActRIIa and ActRIIb was cloned and characterized. Overexpression of ActRIIb in zebrafish embryos caused dorsalization of embryos, as observed in activin-overexpressing embryos. However, in blastula stage embryos, ActRIIb induced formation of both dorsal and ventro-lateral mesoderm. It has been suggested that these inducing signals from ActRIIb are mediated through each specific type I receptor, TARAM-A and BMPRIA, depending on activin and bone morphogenetic protein (BMP), respectively. In addition, it was shown that a kinase-deleted form of ActRIIb (dnActRIIb) suppressed both activin- and BMP-like signaling pathways. These results suggest that ActRIIb at least has dual roles in both activin and BMP signaling pathways during zebrafish embryogenesis.

Activin Receptors, Type II↗
PubMed1999

Endoscopic sphincter dilation in patients with bile duct stones: immediate and medium-term results.

BACKGROUND: Endoscopic sphincter dilation (ESD) is believed to successfully treat bile duct stones without serious procedure-related complications. METHODS: We evaluated the efficacy, safety and limitations of this relatively new procedure in a consecutive series of patients to establish the clinical role of this modality for treating bile duct stones. One hundred and forty-three consecutive patients were treated by ESD between July 1995 and March 1998. The balloons used were a Maxforce 5-Fr or Olbert 5-Fr balloon-tipped catheter with a maximal diameter of 8 mm. Mechanical lithotriptor (ML) or extracorporeal shock wave lithotripsy (ESWL) were used when stones were large and/or numerous and a Dormia basket or retrievable balloon catheter was used to extract the stones entirely. Procedure-related symptoms and chemical data after the procedure were monitored during and after ESD at least until the following morning. To diagnose residual stones accurately, intraductal ultrasonography was routinely used. RESULTS: Although the majority of patients complained of subtle pain during balloon inflation and demonstrated oozing during and after balloon inflation, the procedures were well tolerated. Complete stone extraction was achieved in 139 (97.2%) of the patients. Mechanical lithotriptor and ESWL were used to assist stone clearance in 79 (55.2%) and 23 (16.1%) patients, respectively. Mild pancreatitis occurred in six patients (4.2%). However, there were no other serious complications. Stone recurrence was identified in six patients and these stones were re-extracted by subsequent ESD procedures. CONCLUSIONS: A high success rate for stone extraction and the relative safety of this procedure was confirmed. However, there was recurrence in a relatively high percentage of patients within a short period and this may be a forthcoming issue in ESD. Long-term follow-up observation and the establishment of countermeasures for stone recurrence seem to be essential.

Adult↗
PubMed1999

Intracerebroventricularly administered corticotropin-releasing factor inhibits food intake and produces anxiety-like behaviour at very low doses in mice.

AIM: Previous studies have demonstrated that corticotropin-releasing factor (CRF) produces behavioural, physiological and immunological responses similar to those induced by stress. However, these findings have been validated largely in laboratory rats. METHODS: We examined the effects of intracerebroventricular (i.c.v.) administration of CRF on anxiety and food intake in mice. Using the elevated-plus maze, we measured anxiety levels after i.c.v. CRF in mice. We also measured food intake for 2 h after i.c.v. CRF. RESULTS: CRF increased the normal preference for the closed arms of the maze at a very low dose of 3 pmol, indicating an anxiogenic effect. CRF powerfully suppressed food intake at the doses of 3-300 pmol for over 2 h. CONCLUSION: Our results demonstrate that i.c.v. CRF evokes anxiogenic behaviour and suppresses feeding with the same dose-response relationships in mice. CRF may thus play a role in integrating the overall responses to stress through co-ordinated actions in the brain of this species.

Animals↗
PubMed1999

Influence of bile duct diameter on the therapeutic quality of endoscopic balloon sphincteroplasty.

BACKGROUND AND STUDY AIMS: Endoscopic balloon sphincteroplasty (EBS) has been reported to be a safe alternative to sphincterotomy for the treatment of bile duct stones. We evaluated the factors which influence the therapeutic efficacy of EBS. PATIENTS AND METHODS: A total of 118 consecutive patients with bile duct stones were treated by EBS. After conventional endoscopic retrograde cholangiography (ERC), EBS was done using a biliary dilation catheter (balloon diameter, 8mm). The duct was then cleared using Dormia baskets or retrievel balloon catheters. When the stones were greater than 8 mm in diameter, mechanical lithotripsy was performed before extraction. Complete stone clearance was assessed by balloon-ERC and intraductal ultrasonography. Therapeutic efficacy was assessed using univariate and multivariate analysis. Patients were classified into three groups according to the bile duct diameter: nondilated (bile duct < or = 10 mm), mildly dilated (10 mm < bile duct < or = 15 mm), and severely dilated group (bile duct > 15 mm). RESULTS: In 113 of 118 (96%) patients, the stones were completely cleared with one to six endoscopic sessions (mean 1.6 sessions). In the nondilated group, 24 of 28 (85%) patients were cleared of stones in one session (mean 1.2 sessions), without the use of mechanical lithotripsy in 23 of 28 (82 %) patients. In the mildly dilated group, 23 of 38 (61 %) patients were cleared of stones in one session (mean 1.5 sessions). In contrast, in the severely dilated group, only 16 of 52 (31 %) patients were cleared of stones in one session (mean 2.0 sessions). Stone size, number of stones, and use of mechanical lithotripsy were independent variables which influenced the success of stone clearance in one session after EBS. CONCLUSION: When EBS is done in patients with bile duct stones, bile duct diameter may be a good indicator of therapeutic efficacy. In patients with severely dilated bile ducts (> 15 mm), EBS is of limited effectiveness.

Aged↗
PubMed1999

p38 mitogen-activated protein kinase can be involved in transforming growth factor beta superfamily signal transduction in Drosophila wing morphogenesis.

p38 mitogen-activated protein kinase (p38) has been extensively studied as a stress-responsive kinase, but its role in development remains unknown. The fruit fly, Drosophila melanogaster, has two p38 genes, D-p38a and D-p38b. To elucidate the developmental function of the Drosophila p38's, we used various genetic and pharmacological manipulations to interfere with their functions: expression of a dominant-negative form of D-p38b, expression of antisense D-p38b RNA, reduction of the D-p38 gene dosage, and treatment with the p38 inhibitor SB203580. Expression of a dominant-negative D-p38b in the wing imaginal disc caused a decapentaplegic (dpp)-like phenotype and enhanced the phenotype of a dpp mutant. Dpp is a secretory ligand belonging to the transforming growth factor beta superfamily which triggers various morphogenetic processes through interaction with the receptor Thick veins (Tkv). Inhibition of D-p38b function also caused the suppression of the wing phenotype induced by constitutively active Tkv (TkvCA). Mosaic analysis revealed that D-p38b regulates the Tkv-dependent transcription of the optomotor-blind (omb) gene in non-Dpp-producing cells, indicating that the site of D-p38b action is downstream of Tkv. Furthermore, forced expression of TkvCA induced an increase in the phosphorylated active form(s) of D-p38(s). These results demonstrate that p38, in addition to its role as a transducer of emergency stress signaling, may function to modulate Dpp signaling.

Animals↗
PubMed1999

Extracellular matrix-associated bone morphogenetic proteins are essential for differentiation of murine osteoblastic cells in vitro.

Osteoblastic differentiation is an essential part of bone formation that compensates resorbed bone matrix to maintain its structural integrity. Cells in an osteoblast lineage develop differentiated phenotypes during a long-term culture in vitro. However, intrinsic mechanisms whereby these cells differentiate into mature osteoblasts are yet unclear. Bone morphogenetic proteins (BMPs) stimulate osteoblastic differentiation and bone formation. We demonstrate that mouse osteoblastic MC3T3-E 1 cells constitutively expressed messenger RNAs (mRNAs) for BMP-2 and BMP-4 and accumulated BMPs in collagen-rich extracellular matrices. BMPs associated with the extracellular matrices were involved in the induction of osteoblastic differentiation of nonosteogenic mesenchymal cells as well as cells in the osteoblast lineage. MC3T3-E1 cells constitutively expressed type IA and type II BMP receptors. When a kinase-deficient type IA BMP receptor was stably transfected to MC3T3-E 1 cells to obliterate BMP-2/4 signaling, these cells not only failed to respond to exogenous BMP-2 but lost their capability of differentiation into osteoblasts that form mineralized nodules. These observations strongly suggest that endogenous BMP-2/4 accumulated in extracellular matrices are essential for the osteoblastic differentiation of cells in the osteoblast lineage. Therefore, the regulatory mechanism of BMP-2/4 actions in osteoblastic cells is a principal issue to be elucidated for better understanding of pathogenesis of bone losing diseases such as osteoporosis.

Animals↗
PubMed1999

In vivo analysis using variants of zebrafish BMPR-IA: range of action and involvement of BMP in ectoderm patterning.

It has been an intriguing problem whether the polypeptide growth factors belonging to the transforming growth factor-beta (TGF-beta) superfamily function as direct and long-range signaling molecules in pattern formation of the early embryo. In this study, we examined the mechanism of signal propagation of bone morphogenetic protein (BMP) in the ectodermal patterning of zebrafish embryos, in which BMP functions as an epidermal inducer and a neural inhibitor. To estimate the effective range of zbmp-2, we first performed whole-mount in situ hybridization analysis. The zbmp-2-expressing domain and the neuroectoderm, marked by otx-2 expression, were complementary, suggesting that BMP has a short-range effect in vivo. Moreover, mosaic experiments using a constitutively active form of a zebrafish BMP type I receptor (CA-BRIA) demonstrated that the cell-fate conversion, revealed by ectopic expression of gata-3 and repression of otx-2, occurred in a cell-autonomous manner, denying the involvement of the relay mechanism. We also found that zbmp-2 was induced cell autonomously within the transplanted cells in the host ectoderm, suggesting that BMP cannot influence even the neighboring cells. This result is consistent with the observation that there is no gap between the expression domains of zbmp-2 and otx-2. Taken together, we propose that, in ectodermal patterning, BMP exerts a direct and cell-autonomous effect to fate uncommitted ectodermal cells to become epidermis.

Amino Acid Sequence↗
PubMed1999

Regulation of body length and male tail ray pattern formation of Caenorhabditis elegans by a member of TGF-beta family.

We have identified a new member of the TGF-beta superfamily, CET-1, from Caenorhabditis elegans, which is expressed in the ventral nerve cord and other neurons. cet-1 null mutants have shortened bodies and male tail abnormal phenotype resembling sma mutants, suggesting cet-1, sma-2, sma-3 and sma-4 share a common pathway. Overexpression experiments demonstrated that cet-1 function requires wild-type sma genes. Interestingly, CET-1 appears to affect body length in a dose-dependent manner. Heterozygotes for cet-1 displayed body lengths ranging between null mutant and wild type, and overexpression of CET-1 in wild-type worms elongated body length close to lon mutants. In male sensory ray patterning, lack of cet-1 function results in ray fusions. Epistasis analysis revealed that mab-21 lies downstream and is negatively regulated by the cet-1/sma pathway in the male tail. Our results show that cet-1 controls diverse biological processes during C. elegans development probably through different target genes.

Amino Acid Sequence↗
PubMed1999

[Exercise-induced acute renal failure associated with renal vasoconstriction].

Exercise-induced acute renal failure without rhabdomyolysis is not a rare condition. We experienced 6 cases (5 men and a woman) during last the 8 years. All cases complained of severe loin pain and nausea after mild to moderate exercises (for example, a track race in an athletic meeting). The elevation of serum and urinary myoglobin was undetected. In 4 of 5 patients with abdominal CT, renal patchy vasoconstriction (wedge-shaped low-density lesion) was observed. This was diagnosed as exercise-induced acute renal failure with loin pain (serum creatinine levels: 1.7-8.6 mg/dl). The renal function in 5 of the 6 cases normalized in about three weeks by fluid replacement therapy and hemodialysis support, which one patient received for 3 days. One patient required a long time for improvement of renal function and renal insufficiency persisted (serum creatinine 1.8 mg/dl). In 2 patients, the concentration of serum uric acid became very low after the recovery of renal function. These two patients were diagnosed as an isolated hyperuricosuric hypouricemia. More than half of the 6 patients had previously experienced the same episodes (loin pain and nausea) after exercise. Exercise-induced acute renal failure, probably due to renal patchy vasoconstriction, seems to be not a rare disease. The etiology of renal patchy vasoconstriction after exercises remains to be elucidated. The occurrence of acute renal failure must be taken into consideration when the youngster, especially with renal hypouricemia, complains of severe loin pain and nausea after exercise such as a track race.

Acute Kidney Injury↗
PubMed1998

Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo.

In early development of Xenopus laevis, it is known that activities of polypeptide growth factors are negatively regulated by their binding proteins. In this study, follistatin, originally known as an activin-binding protein, was shown to inhibit all aspects of bone morphogenetic protein (BMP) activity in early Xenopus embryos. Furthermore, using a surface plasmon resonance biosensor, we demonstrated that follistatin can directly interact with multiple BMPs at significantly high affinities. Interestingly, follistatin was found to be noncompetitive with the BMP receptor for ligand binding and to form a trimeric complex with BMP and its receptor. The results suggest that follistatin acts as an organizer factor in early amphibian embryogenesis by inhibiting BMP activities by a different mechanism from that used by chordin and noggin.

Animals↗
PubMed1998

Endomorphins have orexigenic and anxiolytic activities in mice.

This study was designed to investigate the effects of endomorphin 1 and 2, recently identified mu-opioid receptor selective peptides, on food intake and anxiety in non-food-deprived mice. The intracerebroventricular (i.c.v.) injection of either endomorphin 1 or 2 (0.03-30 nmol) increased food intake in a dose-related manner. A significant increase was observed 20 min after i.c.v. injection of endomorphin 1 or 2 and continued for 4 h. In the elevated plus maze test, the i.c.v. injection of endomorphin 1 (30 nmol) significantly decreased the normal preference for the closed arms. These results suggest that endomorphin produces orexigenic and anxiolytic effects, and that the mu-opioid receptor contributes to the regulation of feeding and anxiety in mice.

Animals↗
PubMed1998

Angle-resolved UV photoelectron spectra (UPS) of thin films of perylene-3,4,9,10-tetracarboxylic dianhydride on MoS(2).

Angle-resolved UV photoelectron spectra (ARUPS) were measured for thin films of perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) deposited on cleaved MoS(2) surfaces. The take-off angle (theta) dependence of the photoelectron intensity of the highest pi band showed a sharp maximum at theta = 32-34 degrees. A spectral feature of the binding energy at approximately 8.9 eV, which is believed to originate from a pi state, showed a remarkably different theta dependence from that of the pi band. A quantitative analysis of the observed theta dependencies clearly indicates that (a) the feature at approximately 8.9 eV originates from the oxygen 2p non-bonding states and (b) the molecules lie flat on the substrate surface.

Journal Article↗
PubMed1998

Temperature dependence of photoelectron angular distribution from thin films of chloroaluminum phthalocyanine on MoS(2).

Angle-resolved UV photoelectron spectra were measured for thin films of chloroaluminum phthalocyanine deposited on cleaved MoS(2) surfaces. The take-off angle (theta) dependence of the photoelectron intensity of the highest pi band showed a remarkable sharpening upon cooling the film, indicating that thermal excitation of molecular vibrations gives a considerable broadening of the photoelectron angular distribution. The theta dependence observed at approximately 120 K agrees well with that calculated.

Journal Article↗
PubMed1998

Role of TAK1 and TAB1 in BMP signaling in early Xenopus development.

Transforming growth factor-beta (TGF-beta) superfamily members elicit signals through stimulation of serine/threonine kinase receptors. Recent studies of this signaling pathway have identified two types of novel mediating molecules, the Smads and TGF-beta activated kinase 1 (TAK1). Smads were shown to mimic the effects of bone morphogenetic protein (BMP), activin and TGF-beta. TAK1 and TAB1 were identified as a MAPKKK and its activator, respectively, which might be involved in the up-regulation of TGF-beta superfamily-induced gene expression, but their biological role is poorly understood. Here, we have examined the role of TAK1 and TAB1 in the dorsoventral patterning of early Xenopus embryos. Ectopic expression of Xenopus TAK1 (xTAK1) in early embryos induced cell death. Interestingly, however, concomitant overexpression of bcl-2 with the activated form of xTAK1 or both xTAK1 and xTAB1 in dorsal blastomeres not only rescued the cells but also caused the ventralization of the embryos. In addition, a kinase-negative form of xTAK1 (xTAK1KN) which is known to inhibit endogenous signaling could partially rescue phenotypes generated by the expression of a constitutively active BMP-2/4 type IA receptor (BMPR-IA). Moreover, xTAK1KN could block the expression of ventral mesoderm marker genes induced by Smad1 or 5. These results thus suggest that xTAK1 and xTAB1 function in the BMP signal transduction pathway in Xenopus embryos in a cooperative manner.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Effect of the Kobe earthquake on stress and glycemic control in patients with diabetes mellitus.

OBJECTIVE: To examine the effects of the Kobe, Japan, earthquake, a life-threatening event, on stress and glycemic control in diabetic patients. PATIENTS AND METHODS: Hemoglobin A1c levels before and after the earthquake were evaluated in diabetic patients in Kobe (N = 157; magnitude, 7.2) and in Osaka, Japan, as a control (N = 277; magnitude, 4.2), where little damage to houses and traffic facilities occurred. Glycosylated hemoglobin levels were also compared with those of 2 years before and 1 year after the earthquake. The General Health Questionnaire (GHQ) and a self-administered questionnaire regarding damage to houses and relatives killed or injured were used to assess psychological and mental stresses on earthquake survivors. RESULTS: Glycemic control was aggravated in diabetic patients after the earthquake in Kobe but not in Osaka. THe GHQ scores were significantly higher in the patients in Kobe than those in Osaka. Increased hemoglobin A1c concentrations and high scores on the GHQ were especially evident in diabetic patients with severe damage to houses and/or with relatives killed or injured. CONCLUSION: These results suggest an association between chronic, life-threatening stress and the worsening of metabolic control in patients with diabetes mellitus.

Adult↗
PubMed1998

Effect of age on brown adipose tissue activity in the obese (ob/ob) mouse.

Brown adipose tissue (BAT), a highly thermogenic tissue in young animals, is relatively atrophied and thermogenetically quiescent (e.g. as measured by colonic temperature) in mice that are obese or old. The aim of the current study was to investigate the effect of aging (3.1 (young) versus 14.6 (old) months old) on BAT activity in lean and obese (ob/ob) mice. In young but not in old mice, BAT mass in terms of weight per unit body weight was significantly lower in obese mice than in lean mice. A significant increase in BAT mass of obese mice with age was noted in terms of weight or weight per unit body weight, probably because of a tendency to become white adipose tissue and the deposit of fat, accompanied by the lowest levels of total protein, guanosine 5'-diphosphate binding, and uncoupling protein (UCP) antigen in the mitochondria of BAT, as well as the lowest colonic temperature among the groups examined. Unlike old lean animals, the old obese (ob/ob) animals did not increase but rather decreased the expression of mRNA for UCP in the mitochondria of BAT. These findings suggest that a marked decrease in BAT thermogenic capacity and activity is noted in old obese mice, probably due to synergism of aging and obesity.

Adipose Tissue, Brown↗
PubMed1998

Characterization of biliary strictures using intraductal ultrasonography: comparison with percutaneous cholangioscopic biopsy.

BACKGROUND: We determined the accuracy of intraductal ultrasonography (IDUS) in distinguishing between bile duct cancer and benign bile duct disease. METHODS: Patients (n=42) who required bile duct biopsy using percutaneous transhepatic cholangioscopy (PTCS) to evaluate bile duct strictures or filling defects were studied. A thin-caliber ultrasonic probe (2.0 mm diameter and 20 MHz frequency) was inserted into the bile duct, and its images were prospectively reviewed before PTCS. RESULTS: Disruption of the bile duct wall structure, seen on IDUS, was associated with malignancy in 25 of 26 patients. When IDUS demonstrated a lesion with normal bile duct structure, six of nine patients were found to have no malignancy. IDUS demonstrated no intraductal lesion in seven patients, and bile duct biopsy also did not indicate cancer in any of these patients. The accuracy, sensitivity, and specificity of IDUS for diagnosing bile duct cancer were 76%, 89%, and 50%, respectively. When used in tandem with IDUS, the sensitivity of bile cytology (64%) and PTCS (93%) improved to 96% and 100%, respectively. CONCLUSIONS: The accuracy of IDUS for diagnosing bile duct cancer was less than that of PTCS (95%). However, the sensitivity for bile cytology, or bile duct biopsy improved when performed in combination with IDUS.

Adult↗