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Biomedical subjects

N Ueno

Publications and source records attributed to N Ueno.

At least 163 records · Page 9Linked to original sources

Developmental changes in alpha 1-adrenergic receptors, IP3 responses, and NE-induced contraction in cerebral arteries.

Cerebral arteries show significant developmental and artery-specific changes in noradrenergic-mediated contraction. To test the hypothesis that these changes result from differences in the density of alpha 1-adrenergic receptors (alpha 1-ARs) and/or norepinephrine (NE)-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P3,IP3] synthesis, we quantified these variables and the NE-induced contraction in the common carotid artery (Com) and main branch cerebral arteries (MBC) from term fetal (approximately 140 gestational day) and newborn (2- to 5-day) sheep and compared them with adult values. In fetal and newborn Com, maximal contractions to NE (percent K+ maximum response) were 132 +/- 14 and 118 +/- 9%, respectively (adult = 92 +/- 7%). For fetal and newborn middle cerebral artery, these values were 34 +/- 10 and 43 +/- 7%, respectively (adult = 24 +/- 7%). alpha 1-AR density values in Com of fetal and newborn sheep were 113 +/- 18 and 106 +/- 4 fmol/mg protein, respectively (adult = 54 +/- 3 fmol/mg protein). For the MBC, density values were 47 +/- 2 and 24 +/- 3 fmol/mg protein, respectively (adult = 23 +/- 3 fmol/protein). In term fetal and newborn MBC, NE produced dose-dependent increases in Ins(1,4,5)P3, the maximal increases above basal values being 245 +/- 40 and 189 +/- 16%, respectively (adult = 254 +/- 35%). Neither fetus nor newborn Com showed significant Ins(1,4,5)P3 responses to NE. We concluded that in fetal and newborn Com and MBC, alpha 1-AR density and NE-induced Ins(1,4,5)P3 response varied as a function of developmental age and specific vessel. However, these variations did not correlate with NE-induced maximum contraction. Thus we reject the hypothesis that age-dependent and vessel-specific differences of cerebral artery adrenergic-mediated contraction are a function of alpha 1-AR density or Ins(1,4,5)P3 response. Rather, the differences would appear to result from other factors such as non-Ins(1,4,5)P3-mediated calcium activation and/or sensitivity to Ins(1,4,5)P3. The studies also suggest considerable potential for maturational modulation of pharmacomechanical coupling and homeostatic regulation of cerebrovascular tone.

Aging↗

BMP-2/-4 mediate programmed cell death in chicken limb buds.

During limb development, the mesenchymal cells in restricted areas of limb bud, anterior necrotic zone, posterior necrotic zone, opaque zone and interdigital necrotic zones, are eliminated by programmed cell death. The transcripts of bone morphogenetic protein (Bmp)-2 and -4 were first detected in the areas where cell death was observed, then showed overlapping expression with the programmed cell death zones except the opaque zone. To investigate the function of BMP-2 and BMP-4 during limb pattern formation, the dominant negative form of BMP receptor was overexpressed in chick leg bud via a replication-competent retrovirus to block the endogenous BMP-2/-4 signaling pathway. This resulted in excess web formation at the anterior and posterior regions of limb buds in addition to marked suppression of the regression of webbing at the interdigital regions. Significant reductions in the number of apoptotic cells in these three necrotic zones were found in the limb buds which received the virus carrying dominant negative BMP receptor. This indicates that extra tissue formation is due to suppression of programmed cell death in the three necrotic zones. Moreover, BMP-2/-4 protein induced apoptosis of mesenchymal cells isolated from the interdigital region in vitro. Other TGFbeta family proteins as TGFbeta1 and Activin did not show this effect. These results suggest that BMP-2 and BMP-4 are the apoptotic signal molecules of the programmed cell death process in the chick limb buds.

Animals↗

The usefulness of ultrasonic microprobe imaging for endoscopic variceal ligation.

OBJECTIVES: This study investigated whether ultrasonic microprobe (UMP) imaging was useful in judging the therapeutic effect of endoscopic variceal (EVL) on varices as well as assessing varices and surrounding vessels before and after EVL. METHODS: UMP imaging was performed repeatedly safely and easily via the biopsy channel of an endoscope in 20 patients with esophageal varices. Using this modality in combination with our method of "intensive ligation," we treated esophageal varices successfully. RESULTS: Before EVL, UMP imaging displayed esophageal varices, periesophageal collaterals, and the azygous vein as echo-free lumens. In 15 of 20 patients, UMP imaging clearly detected the perforating vein, one of the optimal ligation sites for EVL, connecting the varix and collateral vein. Just after EVL, UMP imaging revealed a hyperechoic change ("snow ball" sign or "snow channel" sign), indicating blood flow stasis in the esophageal varices. On subsequent EVL, UMP imaging showed the cross-sectional area of varices was undetectable (occluded) or partially detectaable. After repeated EVL (2.9 treatment sessions on average), UMP imaging, as well as endoscopy, indicated that almost all varices were eradicated (undetectable). However, UMP imaging demonstrated that neither collaterals nor the azygous vein had significantly changed in size. CONCLUSIONS: This modern diagnostic modality provided a clinical adjunct to current endoscopy when observing esophageal varices and surrounding vessels before and after EVL to determine the need for additional therapy.

Aged↗

Utility of endoscopic ultrasonography with color Doppler function for the diagnosis of islet cell tumor.

OBJECTIVE: To evaluate the efficacy of endoscopic ultrasonography with color Doppler function for the diagnosis of islet cell tumor. METHODS: Endoscopic ultrasonography was compared with other modalities such as ultrasonography, computed tomography, and angiography in the evaluation of seven patients with islet cell tumor and 28 patients with duct cell cancer. RESULTS: In cases of islet cell tumor, the tumor detection rates by ultrasonography and endoscopic ultrasonography were 86% and 100%, respectively. Color signals were detected in 14% and 100% of the cases of islet cell tumor by ultrasonography and endoscopic ultrasonography, respectively. The pattern of color signals obtained was rich and abundant, showing pulsatile and/or continuous wave patterns. Angiography and computed tomography showed hypervascularity. However, in cases of duct cell cancer, the tumor detection rates by ultrasonography and endoscopic ultrasonography were 96% and 100%, respectively, whereas color signals were detected in 78% with both ultrasonography and endoscopic ultrasonography. The image of blood flow, which was connected to surrounding vessels, showed a linear pattern and few blood flow signals. In these cases, angiography and computed tomography demonstrated encasement of the artery or portal vein without hypervascularity. CONCLUSIONS: Endoscopic ultrasonography was usefull for the localization and differential diagnosis of islet cell tumor because of its excellent ability to visualize small lesions and tumor vascularity simultaneously.

Adenoma, Islet Cell↗

Assessment of arterial invasion in pancreatic cancer using color Doppler ultrasonography.

OBJECTIVE: We report the first study on the value of color Doppler ultrasonography (CDUS) in assessing arterial invasion of pancreatic cancer. METHODS: The relationships between tumors and surrounding major splanchnic arteries (celiac, superior mesenteric, common hepatic, splenic, and gastroduodenal arteries) were preoperatively evaluated with CDUS in 33 consecutive patients with pancreatic cancer. When a tumor partially or completely surrounded the artery, the invasion was diagnosed as positive. Imaging results were then compared with angiographic, surgical, and histopathological findings. RESULTS: In 22 nonsurgical patients, the correspondence rate of CDUS with angiography for the presence of invasion, absence of invasion, and overall was 78%, 95%, and 88%, respectively. In 11 surgical patients, a sensitivity of 60%, specificity of 93%, and accuracy of 87% for detection of arterial invasion were obtained in comparing CDUS with surgical and histopathological findings. There was no significant difference between the accuracy of CDUS and that of CT, or that of angiography. However, the accuracy of CDUS was higher than that of CT (72%) and equal to that of angiography (91%). CONCLUSION: Color Doppler ultrasonography is useful for detecting arterial invasion in pancreatic cancer. It may make angiography unnecessary, especially with advanced tumors, if thorough evaluation for the large artery invasion is performed initially.

Adult↗

Diagnosis of gallbladder carcinoma with color Doppler ultrasonography.

A 65-yr-old woman was referred to our department for evaluation of a gallbladder lesion detected at another institution, where she was diagnosed with chronic cholecystitis. Conventional ultrasonography revealed that the gallbladder lumen was filled with debris-like components, and the gallbladder wall was mildly thickened. Color Doppler ultrasonography revealed color signals in both the lesion and the gallbladder wall. These signals showed a high-speed pulsatile wave, and one of the visualized signals revealed a high-resistance index (1.0) on fast Fourier transform analysis. These findings were highly suggestive of malignancy. Surgery was performed, and histological examination of the resected specimen revealed carcinoma of the gallbladder. We conclude that color Doppler ultrasonography can be useful in the diagnosis of tumefactive gallbladder lesions.

Adenocarcinoma↗

[Progress and clinical usefulness of color Doppler method in diagnosing abdominal diseases].

We report the clinical usefulness of extracorporeal color Doppler ultrasonography (CDUS), color Doppler endoscopic ultrasonography (CDEUS), and recent progress in diagnosing abdominal diseases by the color Doppler method. CDUS has the advantage of being able to be performed repeatedly and noninvasively, it is thought to be useful for the evaluation of tumor vascularity and diagnosis of vascular tumor invasion and analysis of hemodynamics in abnormal vessels found in several abdominal diseases. CDEUS, which is performed under endoscopic ultrasonography (EUS), can evaluate the hemodynamics more minutely and visualize small vessels more clearly than conventional CDUS. Recent progress in the color Doppler method, such as US color angiography and the use of contrast agents is expected to lead to a higher resolution of visualization and easier detection of abdominal vessels.

Abdomen↗

[Suitable measure for medicines resulting from pharmacist-visit and assistance for a good treatment].

Our medication team, consists doctors, nurses, pharmacists, and other staffs, made an effort to satisfy our patients with medical treatment. We especially tried to guarantee patient rights. Pharmacists visited patients in September 1995, seeking to inform every patient about effects and side effects of medicines using the "Medicine Information Sheet" with samples. As a result, in one case now under treatment by medicine, he no longer needs it. Then, our medication team had a conference and his doctor changed his prescription. In another case, we found a symptom suspected to be a side effect of a medicine. We asked his doctor about it, and he stopped the medicine in question. His medical condition then became better. This resulted in a "suitable amount" of medicine. We are confident that this is also necessary for every patient under treatment at home, when a pharmacist visits his or her home and informs them about the effects and side effects of medicines, and assists them to assure good treatment.

Aged↗

Vitreous changes during ocular inflammation induced by interleukin 1 beta.

To determine the mechanisms of vitreous changes during ocular inflammation, we investigated these changes, focusing on the collagen, in an experimental model of ocular inflammation induced by intravitreal injection of interleukin 1 beta in rabbits. Inflammation caused gel contraction, with release of a watery liquid from the gel, and increases in the amount of insoluble material and high-molecular-weight components of the vitreous collagen, presumably due to extensive cross-links of the collagen molecules. The cross-links of vitreous collagen may promote vitreous gel contraction and the release of watery liquid from the gel.

Animals↗

Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction.

The mitogen-activated protein kinase (MAPK) pathway is a conserved eukaryotic signaling module that converts receptor signals into various outputs. MAPK is activated through phosphorylation by MAPK kinase (MAPKK), which is first activated by MAPKK kinase (MAPKKK). A genetic selection based on a MAPK pathway in yeast was used to identify a mouse protein kinase (TAK1) distinct from other members of the MAPKKK family. TAK1 was shown to participate in regulation of transcription by transforming growth factor-beta (TGF-beta). Furthermore, kinase activity of TAK1 was stimulated in response to TGF-beta and bone morphogenetic protein. These results suggest that TAK1 functions as a mediator in the signaling pathway of TGF-beta superfamily members.

Amino Acid Sequence↗

Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis.

Bone morphogenetic proteins (BMPs) are secreted proteins that interact with cell-surface receptors and are believed to play a variety of important roles during vertebrate embryogenesis. Bmpr, also known as ALK-3 and Brk-1, encodes a type I transforming growth factor-beta (TGF-beta) family receptor for BMP-2 and BMP-4. Bmpr is expressed ubiquitously during early mouse embryogenesis and in most adult mouse tissues. To study the function of Bmpr during mammalian development, we generated Bmpr-mutant mice. After embryonic day 9.5 (E9.5), no homozygous mutants were recovered from heterozygote matings. Homozygous mutants with morphological defects were first detected at E7.0 and were smaller than normal. Morphological and molecular examination demonstrated that no mesoderm had formed in the mutant embryos. The growth characteristics of homozygous mutant blastocysts cultured in vitro were indistinguishable from those of controls; however, embryonic ectoderm (epiblast) cell proliferation was reduced in all homozygous mutants at E6.5 before morphological abnormalities had become prominent. Teratomas arising from E7.0 mutant embryos contained derivatives from all three germ layers but were smaller and gave rise to fewer mesodermal cell types, such as muscle and cartilage, than controls. These results suggest that signaling through this type I BMP-2/4 receptor is not necessary for preimplantation or for initial postimplantation development but may be essential for the inductive events that lead to the formation of mesoderm during gastrulation and later for the differentiation of a subset of mesodermal cell types.

Alleles↗

Induction of apoptotic cell death by pancreatitis-associated ascitic fluid in Madin-Darby canine kidney cells.

We investigated the cytotoxicity on Madin-Darby canine kidney (MDCK) cells of pancreatitis-associated ascitic fluid (PAAF) collected from rats with experimental necrotizing pancreatitis. PAAF reduced viability of MDCK cells in a time- and dose-dependent manner. We detected DNA fragmentation on the PAAF-treated MDCK cells, indicating that the cytocidal action of PAAF is via apoptosis. From the results obtained, we conclude that PAAF contains factor(s) inducing apoptosis on MDCK cells, and we assume that apoptotic cell death is involved in the mechanism of organ failure in acute pancreatitis.

Acute Disease↗

Developmental and differential regulations in gene expression of Xenopus pleiotrophic factors-alpha and -beta.

Using conserved nucleotide sequences in mammalian osteoblast specific factor-1 (OSF-1) coding regions, we isolated two kinds of cDNA clones from the Xenopus brain library. The encoded proteins, named Xenopus pleiotrophic factors (X-PTFs)-alpha and -beta, were 65 and 87% homologous to human midkine and OSF-1, respectively. In the adult frog, X-ptf-alpha was expressed in the ovary, brain, eye, bone, heart and lung, whereas X-ptf-beta was expressed in the brain, eye and bone. By in situ hybridization of the tailbud embryo, X-ptf-alpha mRNA was detected rather broadly in the head/tail regions including the central nervous system (CNS), whereas X-ptf-beta mRNA was restricted to the CNS, particularly in the hind-brain. During embryogenesis, X-ptf-alpha mRNA was detected in the one-cell stage embryo, whereas only zygotic expression was observed in X-ptf-beta. X-ptf-beta mRNAs contained approximately 79 bp tandem repeats in the 3'-untranslated region, complementary to those found in retinoic acid cellular receptor mRNA and in the sense strand of short interspersed repeat transcripts in X. laevis.

Aging↗

Involvement of the MAP kinase cascade in Xenopus mesoderm induction.

Mitogen-activated protein kinase (MAPK) is activated by MAPK kinase (MAPKK) in a variety of signaling pathways. This kinase cascade has been shown to function in cell proliferation and differentiation, but its role in early vertebrate development remains to be investigated. During early vertebrate embryogenesis, the induction and patterning of mesoderm are thought to be determined by signals from intercellular factors such as members of the fibroblast growth factor (FGF) family and members of the transforming growth factor-beta family. Here we show that the microinjection of either mRNA encoding a constitutively active mutant of MAPKK or mRNA encoding a constitutively active form of STE11, a MAPKK kinase, leads to the induction of mesoderm in ectodermal explants from Xenopus embryos. Moreover, the expression of MAPK phosphatase-1 (MKP-1, also called CL100) blocks the growth factor-stimulated mesoderm induction. Furthermore, injection of CL100 mRNA into two-cell stage embryos causes severe defects in gastrulation and posterior development. The effects induced by CL100 can be rescued by co-injection of wild-type MAPK mRNA. Thus, the MAPK cascade may play a crucial role in early vertebrate embryogenesis, especially during mesoderm induction.

Animals↗

Molecular cloning and functional analysis of a new activin beta subunit: a dorsal mesoderm-inducing activity in Xenopus.

A cDNA that encodes a new member of the TGF-beta superfamily most similar to activin beta A, beta B, and recently reported beta C has been isolated from Xenopus laevis. Expression of the gene in early embryos suggested its biological importance in Xenopus embryogenesis. Microinjection of a synthetic mRNA transcribed from the cDNA into ventral blastomeres of early Xenopus embryo led to the formation of secondary body axis. Mesodermal marker genes were induced in isolated animal cap by a similar mRNA injection. These results demonstrate that the gene encodes a new member of activin subfamily whose function is closely related to mesoderm induction.

Activins↗