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S Noji

Publications and source records attributed to S Noji.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Four cases of third time operation of coronary artery bypass grafting].

Reoperative coronary artery bypass operations are increasing in frequency. Consequently, an ever-increasing pool of patients now is being seen with need of coronary revascularization for repeated time. Four cases of second reoperation were retrospectively investigated. Until March 1999, 2,563 cases of isolated coronary artery bypass grafting were done at the Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan. Within those cases, 124 cases (4.8%) were reoperated. And among those 124 cases, 4 cases (3.2%) were secondly reoperated. There were one hospital death and two had a perioperative myocardial infarction. All of them needed intraaortic balloon pump support after operation. Three were discharged with relief of the symptoms. The average age at the primary operation was 51.1 years. All these cases, at the primary operation, no ITA graft was used. Two cases were incompletely revascularized, because of coronary arteries were ungraftable. Both at reoperation and at second reoperation, we are trying to make a complete revascularization by all arterial grafts. But because of limited number of arterial graft at repeated operation, all arterial complete revascularization is not done without difficulty. Therefore it is concluded that saphenous vein graft is still needed at repeated operation.

Aged↗
PubMed1999

FGFR2 signaling in normal and limbless chick limb buds.

FGF10 and FGF8, which are reciprocally expressed by the mesoderm and AER of the developing limb bud, have been implicated in limb initiation, outgrowth, and patterning. FGF10 and FGF8 signal through the FGFR2b and FGFR2c alternative splice isoforms, respectively [Ornitz DM, et al. 1996. J Biol Chem 271:15292-15297; Igarashi M, et al. 1998. J Biol Chem 273:13230-13235]. A paracrine signaling loop model has been proposed whereby FGF10 expressed by limb mesoderm signals via ectodermally restricted FGFR2b to regulate FGF8 expression by the apical ectoderm; in turn, FGF8 signals via mesodermally restricted FGFR2c to maintain FGF10 expression [Ohuchi H, et al. 1997. Development 124:2235-2244; Xu X, et al. 1998. Development 125:753-765]. To explore this model, we have examined FGFR2b and FGFR2c mRNA expression, using isoform-specific probes during the early stages of development of the chick limb when limb initiation, AER induction, and outgrowth are occurring. We have found that FGFR2b is expressed by limb ectoderm, including the AER, consistent with paracrine signaling of FGF10. By contrast, FGFR2c is expressed by both mesoderm and ectoderm, indicating that FGF8 has the potential to function in an autocrine as well as paracrine fashion. Indeed, as the limb grows out in response to the AER, FGFR2c expression attenuates in the mesoderm of the progress zone, but is maintained in the AER itself, arguing against exclusive paracrine signaling of FGF8 during limb outgrowth. We also report that transcripts for FGF10, FGFR2b, and FGFR2c are expressed normally in the limb buds of limbless mutant embryos, which fail to form an AER and do not express FGF8. Furthermore, we detect no mutations in exons specific for the FGFR2c or FGFR2b isoforms in limbless embryos. Since gene targeting has shown that expression of FGF8 in limb ectoderm depends on FGF10 [Min H, et al. 1998. Genes Dev 12:3156-3161; Sekine K, et al. 1999. Nature Genet 21:138-141], these results indicate that the product of the limbless gene is required for FGF10 to induce expression of FGF8.

Animals↗
PubMed1999

Fibroblast-growth-factor-induced additional limbs in the study of initiation of limb formation, limb identity, myogenesis, and innervation.

In this review, we focus on the additional limb induced by members of the fibroblast growth factor (FGF) family in the flank of chick embryos. The "additional limb" was first reported 73 years ago by Balinsky in 1925. He grafted otic vesicle to the flank of newt embryos and observed the formation of the "additional limb." In 1995, formation of an additional limb was found to be induced by FGF in the chick embryo. This finding subsequently led to the recent understanding of how the limb bud is initially formed, how the limb position is determined, and how the limb identity is determined. Thus, the additional limb has been recognized as a useful experimental system for the study of limb development and its relation to the regionalization of the body. Furthermore, since limb muscles are formed from cells which have migrated from somites and innervation to them takes place from the spinal cord, the additional limb would also be a powerful tool with which to study the relation of limb morphogenesis to developmental processes of the spinal cord and somites. This review consists of five sections: (1) "Introduction," (2) "How to make additional limbs," (3) "Characteristics of the additional limb," (4) "Studies with the additional limb," and (5) "Concluding remarks." In the second section, techniques to make additional limbs are reviewed, showing that additional limbs can be made by fairly easy manipulation of the chick embryo. In the third section, the characteristics analyzed so far of the additional limb are summarized, focusing on its morphology. In the fourth section, recent studies on the use of the additional limb are reviewed: experiments on the additional limb have been performed to elucidate the mechanisms governing determination of limb identity by Hox codes and the Tbx family and initiation of limb formation by FGF10. In addition, the roles of SF/HGF in the formation of limb muscles have also been investigated using the additional limb. In the near future, the additional limb will be also used in the study of innervation from the spinal cord, and probably migration of neural crest cells.

Animals↗
PubMed1999

Identification of chick rax/rx genes with overlapping patterns of expression during early eye and brain development.

We have isolated chick rax/rx cDNAs, cRaxL (chick Rax/Rx-like) and cRax, (chick Rax) and examined their expression patterns during early eye and brain development. The cRaxL cDNA encodes a 228 amino acid protein that is most closely related to the zebrafish Rx1 and Rx2. The cRax cDNA encodes a 317 amino acid protein, which shares higher homology with the Xenopus Rx. In addition to the homeodomain, the octapeptide and paired tail domains are conserved between the cRax and other vertebrate Rax/Rx, while cRaxL lacks the octapeptide containing N-terminal region which is conserved among all other members of the rax/rx gene family identified so far. The chick rax/rx genes are expressed in overlapping domains in the anterior neural ectoderm which corresponds to the forebrain and retina field, and later in the optic vesicle. cRax mRNA can be detected earlier than cRaxL prior to the formation of the notochord and its expression domain appears broader than that of cRaxL.

Animals↗
PubMed1999

Role of Pax-5 in the regulation of a mid-hindbrain organizer's activity.

The mes-metencephalic boundary (isthmus) has been suggested to act as an organizer in the development of the optic tectum. Pax-5 was cloned as a candidate for regulator of the organizing center. Isthmus-specific expression of Pax-5 and analogy with the genetic cascade in Drosophila suggest that Pax-5 may be at a higher hierarchical position in the gene regulation cascade of tectum development. To examine this possibility, a gain-of-function experiment on Pax-5 was carried out. In ovo electroporation on E2 chick brain with the eucaryotic expression vector that encodes chick Pax-5 cDNA was used. Not only was a considerable amount of Pax-5 expressed ectopically in the transfected brain, but irregular bulging of the neuroepithelium was induced in the diencephalon and mesencephalon. At Pax-5 misexpressing sites, uptake of BrdU was increased. Histological examination of E7 transfected brain revealed that Pax-5 caused transdifferentiation of diencephalon into the tectum-like structure. In the bulges of the E7 mesencephalon, differentiation of laminar structure was repressed when compared to the normal side. In transfected embryos, En-2, Wnt-1 and Fgf8 were up-regulated ectopically, and Otx2 was down-regulated in the diencephalon to mesencephalon. Moreover, Ephrin-A2, which is expressed specifically in the tectum with a gradient highest at the caudal end, is suggested to be involved in pathfinding of the retinal fibers, and was induced in the bulges. When the mouse Fgf8 expression vector was electroporated, Pax-5 and chick Fgf8 were also induced ectopically. These results suggest that Pax-5, together with Fgf8, hold a higher position in the genetic hierarchy of the isthmus organizing center and regulate its activity.

Amino Acid Sequence↗
PubMed1999

Involvement of Wnt-5a in chondrogenic pattern formation in the chick limb bud.

Members of the Wnt family are known to play diverse roles in the organogenesis of vertebrates. The full-coding sequences of chicken Wnt-5a were identified and the role it plays in limb development was examined by comparing its expression pattern with that of two other Wnt members, Wnt-4 and Wnt-11, and by misexpressing it with a retrovirus vector in the limb bud. Wnt-5a expression is detected in the limb-forming region at stage 14, and in the apical ectodermal ridge and distal mesenchyme of the limb bud. The signal was graded along the proximal-distal axis at stages 20-28 and also along the anterior-posterior axis during early stages. It disappeared in the cartilage-forming region after stage 26, and was restricted to the region surrounding the phalanges at stage 34. Wnt-4 and Wnt-11, other members of the Wnt-5a-subclass, were expressed with a distinct spatiotemporal pattern during the later phase. Wnt-4 was expressed in the articular structure and Wnt-11 was expressed in the dorsal and ventral mesenchyme adjacent to the ectoderm. Wnt-5a expression was partially reduced after apical ectodermal ridge removal, whereas Wnt-11 expression was down-regulated by dorsal ectoderm removal. Therefore, expression of these Wnt was differentially regulated by the ectodermal signal. Misexpression of Wnt-5a in the limb bud with the retrovirus resulted in truncation of long bones predominantly in the zeugopod because of retarded chondrogenic differentiation. Distal elements, such as the phalanges and metacarpals, were not significantly reduced in size. These results suggest that Wnt-5a is involved in pattern formation along the proximal-distal axis by regulation of chondrogenic differentiation.

Amino Acid Sequence↗
PubMed1999

FGF10 can induce Fgf8 expression concomitantly with En1 and R-fng expression in chick limb ectoderm, independent of its dorsoventral specification.

The limb bud has a thickened epithelium at the dorsal-ventral boundary, the apical ectodermal ridge (AER), which sustains limb outgrowth and patterning. A secreted molecule fibroblast growth factor (FGF)10 is involved in inducing Fgf8 expression in the prospective AER and mutual interaction between mesenchymal FGF10 and FGF8 in the AER is essential for limb outgrowth. A secreted factor Wnt7a and a homeobox protein Lmx1 are involved in the dorsal patterning of the limb, whereas a homeobox protein Engrailed 1 (En1) is involved in the dorsal-ventral patterning as well as AER formation. Radical fringe (R-fng), a vertebrate homolog of Drosophila fringe was also found to elaborate AER formation in chicks. However, little is known about the molecular interactions between these factors during AER formation. The present study clarified the relationship between FGF10, Wnt7a, Lmx1, R-fng and En1 during limb development using a foil-barrier insertion experiment. It was found that a foil-barrier inserted into the chick prospective wing mesenchyme lateral to the mesonephric duct blocks AER induction. This experiment was expanded by implanting Fgf10-expressing cells lateral to the barrier and examined whether FGF10 could rescue the expression of the limb-patterning genes reported in AER formation. It was found that FGF10 is sufficient to induce Fgf8 expression in the ectoderm of the foil-inserted limb bud, concomitantly with R-fng and En1 expression. However, FGF10 could not rescue the expression of the dorsal marker genes, Wnt7a or Lmx1. Thus, it is suggested that epithelial factors of En1 and R-fng can induce Fgf8 expression in the limb ectoderm in cooperation with a mesenchymal factor FGF10. Some factor(s) other than FGF10, possibly from the paraxial structures medial to the limb mesoderm, is responsible for the initial dorsal-ventral specification of the limb bud.

Animals↗
PubMed1998

lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal.

lefty-1, lefty-2, and nodal are expressed on the left side of developing mouse embryos and are implicated in left-right (L-R) determination. The role of lefty-1 was examined by analyzing mutant mice lacking this gene. The lefty-1-deficient mice showed a variety of L-R positional defects in visceral organs. Unexpectedly, however, the most common feature of lefty-1-/- mice was thoracic left isomerism (rather than right isomerism). The lack of lefty-1 resulted in bilateral expression of nodal, lefty-2, and Pitx2 (a homeobox gene normally expressed on the left side). These observations suggest that the role of lefty-1 is to restrict the expression of lefty-2 and nodal to the left side, and that lefty-2 or nodal encodes a signal for "leftness."

Animals↗
PubMed1998

Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry.

Signaling molecules such as Activin, Sonic hedgehog, Nodal, Lefty, and Vg1 have been found to be involved in determination of left-right (L-R) asymmetry in the chick, mouse, or frog. However, a common signaling pathway has not yet been identified in vertebrates. We report that Pitx2, a bicoid-type homeobox gene expressed asymmetrically in the left lateral plate mesoderm, may be involved in determination of L-R asymmetry in both mouse and chick. Since Pitx2 appears to be downstream of lefty-1 in the mouse pathway, we examined whether mouse Lefty proteins could affect the expression of Pitx2 in the chick. Our results indicate that a common pathway from lefty-1 to Pitx2 likely exists for determination of L-R asymmetry in vertebrates.

Animals↗
PubMed1998

Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants.

Activin, a member of the TGF-beta superfamily, regulates the growth and differentiation of a variety of cell types. Based on the expression of activin in pancreatic rudiments of rat embryos and stimulation of insulin secretion from adult rat pancreatic islets by activin, activin is implicated in the development and function of islets. To examine the significance of activin signaling in the fetal and postnatal development of islets, transgenic mice expressing a dominant negative form of activin receptor (dn-ActR) or a constitutively active form of activin receptor (ActR-T206D) in islets were generated together with the transgenic mice expressing intact activin receptor (intact ActR) as a negative control. Transgenic mice with both dn-ActR and ActR-T206D showed lower survival rates, smaller islet area, and lower insulin content in the whole pancreas with impaired glucose tolerance when compared with transgenic mice with intact ActR or littermates, but they showed the same alpha cell/beta cell ratios as their littermates. In addition to islet hypoplasia, the insulin response to glucose was severely impaired in dn-ActR transgenic mice. It is suggested that a precisely regulated intensity of activin signaling is necessary for the normal development of islets at the stage before differentiation into alpha and beta cells, and that activin plays a role in the postnatal functional maturation of islet beta cells.

Activin Receptors↗
PubMed1998

Expression of peroxisome proliferator-activated receptor alpha (PPAR alpha) in primary cultures of human vascular endothelial cells.

The peroxisome proliferator-activated receptor (PPAR) is a member of the steroid nuclear receptor superfamily. Three types of PPARs have been described in humans: PPAR alpha, PPAR beta, and PPAR gamma. Here we investigated the levels of PPAR alpha mRNA in primary cultures of human umbilical venous endothelial cells (HUVEC), human umbilical arterial endothelial cells (HUAEC), human coronary arterial endothelial cells (HCAEC), and human aortic endothelial cells (HAEC), using the reverse transcriptase-polymerase chain reaction (RT-PCR). The HUVEC, HAEC, and HCAEC, but not the HUAEC, showed relatively low expression of PPAR alpha in comparison with liver, which was used as a positive control. Moreover, the partial sequences of the PCR-amplified products from HUVEC, HAEC, and HCAEC were similar to that of the PPAR alpha from human liver. The expression of PPAR alpha in cultured HAEC, which were induced by dexamethasone, was inhibited by insulin. In addition, PPAR alpha expression was also increased by benzafibrate or eicosapentaenoic acid with the physiological concentration. These results suggest that the PPAR alpha in endothelial cells may have the same physiological role as the expression of PPAR alpha in the liver.

Aorta↗
PubMed1998

Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes.

To examine the role of bone morphogenetic protein (BMP) signaling in chondrocytes during endochondral ossification, the dominant negative (DN) forms of BMP receptors were introduced into immature and mature chondrocytes isolated from lower and upper portions of chick embryo sternum, respectively. We found that control sternal chondrocyte populations expressed type IA, IB, and II BMP receptors as well as BMP-4 and -7. Expression of a DN-type II BMP receptor (termed DN-BMPR-II) in immature lower sternal (LS) chondrocytes led to a loss of differentiated functions; compared with control cells, the DN-BMPR- II-expressing LS chondrocytes proliferated more rapidly, acquired a fibroblastic morphology, showed little expression of type II collagen and aggrecan genes, and upregulated type I collagen gene expression. Expression of DN-BMPR-II in mature hypertrophic upper sternal (US) chondrocytes caused similar effects. In addition, the DN-BMPR-II-expressing US cells exhibited little alkaline phosphatase activity and type X collagen gene expression, while the control US cells produced both alkaline phosphatase and type X collagen. Both DN-BMPR-II-expressing US and LS chondrocytes failed to respond to treatment with BMP-2 . When we examined the effects of DN forms of types IA and IB BMP receptors, we found that DN-BMPR-IA had little effect, while DN-BMPR-IB had similar but weaker effects compared with those of DN-BMPR-II. We conclude that BMP signaling, particularly that mediated by the type II BMP receptor, is required for maintenance of the differentiated phenotype, control of cell proliferation, and expression of hypertrophic phenotype.

Animals↗
PubMed1998

Bezafibrate has an antioxidant effect: peroxisome proliferator-activated receptor alpha is associated with Cu2+, Zn2+-superoxide dismutase in the liver.

Administration of bezafibrate in rats significantly reduced the levels of plasma thiobarbituric acid-reactive substances (TBARS) in comparison with those obtained in rats fed a soy or lard chow. Moreover, an elevation of in vitro conjugated diene production and linoleic acid levels in the high-density lipoproteins and low-density lipoproteins induced by a soy or lard chow, was reduced by bezafibrate administration. In addition, the liver Cu2+, Zn2+-superoxide dismutase (SOD) gene expression showed a significant positive correlation with the liver peroxisome proliferator-activated receptor alpha (PPARalpha) mRNA level (R=0.769, p<0.0001). This unique characteristic of bezafibrate, which possesses both a hypolipidemic effect and antioxidant activity, may be beneficial in preventing vascular complications in hyperlipidemia.

Acyl-CoA Oxidase↗
PubMed1998

Sonic hedgehog expression in developing chicken digestive organs is regulated by epithelial-mesenchymal interactions.

Sonic hedgehog (Shh) gene encodes a secreted protein that acts as an important mediator of cell-cell interactions. A detailed analysis of Shh expression in the digestive organs of the chicken embryo was carried out. Shh expression in the endoderm begins at stage 7, when the formation of the foregut commences, and is found as narrow bands in the midgut. Shh expression around the anterior intestinal portal at stage 15 is restricted to the columnar endoderm lined by the thick splanchnic mesoderm, suggesting that the existence of thick splanchnic mesoderm might be necessary for Shh expression in the columnar endoderm. After the gut is closed, Shh expression is found universally in digestive epithelia, including the cecal epithelium. However, its expression ceases in the epithelium of the proventricular glands, the ductus choledochus and ductus pancreaticus that protrude from the main digestive duct. When the gizzard epithelium differentiated into glands under the influence of the proventricular mesenchyme, the glandular epithelium lost the ability to express Shh. These findings suggest that Shh expression in the epithelium may be regulated by surrounding mesenchyme throughout organogenesis of the digestive organs and is closely involved in epithelial-mesenchymal interactions in developing digestive organs.

Animals↗
PubMed1998

Correlation of wing-leg identity in ectopic FGF-induced chimeric limbs with the differential expression of chick Tbx5 and Tbx4.

It has been reported that members of the fibroblast growth factor (FGF) family can induce additional limb formation in the flank of chick embryos. The phenotype of the ectopic limb depends on the somite level at which it forms: limbs in the anterior flank resemble wings, whereas those in the posterior flank resemble legs. Ectopic limbs located in the mid-flank appear chimeric, possessing characteristics of both wings and legs; feather buds are present in the anterior halves with scales and claws in the posterior halves. To study the mechanisms underlying the chimerism of these additional limbs, we cloned chick Tbx5 and Tbx4 to use as forelimb and hindlimb markers and examined their expression patterns in FGF-induced limb buds. We found that Tbx5 and Tbx4 were differentially expressed in the anterior and posterior halves of additional limb buds in the mid-flank, respectively, consistent with the chimeric patterns of the integument. A boundary of Tbx5/Tbx4 exists in all ectopic limbs, indicating that the additional limbs are essentially chimeric, although the degree of chimerism is dependent on the position. The boundary of Tbx5/Tbx4 expression is not fixed at a specific position within the interlimb region, but dependent upon where FGF was applied. Since the ectopic expression patterns of Tbx5/Tbx4 in the additional limbs are closely correlated with the patterns of their chimeric phenotypes, it is likely that Tbx5 and Tbx4 expression in the limb bud is involved in determination of the forelimb and hindlimb identities, respectively, in vertebrates.

Amino Acid Sequence↗
PubMed1997

Differential expression of the two closely related LIM-class homeobox genes LH-2A and LH-2B during limb development.

We have isolated the chicken homeobox genes LH-2A and LH-2B encoding two related LIM domain-containing homeodomain proteins and examined the expression pattern during chick limb development. LH-2A is most closely related to human and rat LH-2, while LH-2B is less conserved. Although both LH-2A and LH-2B are expressed in the limb mesenchyme throughout stage 16 to stage 32, LH-2A transcripts are detectable in the distal limb bud and LH-2B transcripts are detectable in the anterior limb bud. Signals from the apical ectodermal ridge positively regulate LH-2A expression, since removal of the apical ectoderm resulted in the rapid reduction of LH-2A expression in the distal limb mesenchyme. Ectopic expression of the sonic hedgehog gene in the anterior margin of the limb bud resulted in the rapid reduction of LH-2B expression accompanying respecification of the positional value to the posterior phenotype. These results suggest that LH-2A and LH-2B play important roles in the determination and specification of the proximal-distal and anterior-posterior positional values, respectively.

Amino Acid Sequence↗
PubMed1997

The peroxisome proliferator-activated receptor alpha (PPAR alpha) regulates the plasma thiobarbituric acid-reactive substance (TBARS) level.

We investigated whether liver expression of the peroxisome proliferator-activated receptor alpha (PPAR alpha) gene is related to the plasma thiobarbituric acid-reactive substance (TBARS) level, as well as to plasma cholesterol (TC) level and plasma triglyceride (TG) level in rats fed a high fat chow containing a variety of fatty acids. Only the plasma TBARS level showed a significant negative correlation with the liver PPAR alpha mRNA level (TC, R = 0.001, p = 0.9967; TG, R = 0.248, p = 0.1276; TBARS, R = 0.439, p = 0.0046). Although further studies are needed to clarify whether the increase of the liver PPAR alpha mRNA level confers a reduction in plasma TBARS levels, it is likely that PPAR alpha activity plays a regulatory role in the pathogenesis of hyperlipidemia and atherosclerosis.

Animals↗