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Biomedical subjects

H Ohuchi

Publications and source records attributed to H Ohuchi.

At least 19 recordsLinked to original sources
PubMed1999

FGF7 and FGF10 directly induce the apical ectodermal ridge in chick embryos.

During vertebrate limb development, the apical ectodermal ridge (AER) plays a vital role in both limb initiation and distal outgrowth of the limb bud. In the early chick embryo the prelimb bud mesoderm induces the AER in the overlying ectoderm. However, the direct inducer of the AER remains unknown. Here we report that FGF7 and FGF10, members of the fibroblast growth factor family, are the best candidates for the direct inducer of the AER. FGF7 induces an ectopic AER in the flank ectoderm of the chick embryo in a different manner from FGF1, -2, and -4 and activates the expression of Fgf8, an AER marker gene, in a cultured flank ectoderm without the mesoderm. Remarkably, FGF7 and FGF10 applied in the back induced an ectopic AER in the dorsal median ectoderm. Our results suggest that FGF7 and FGF10 directly induce the AER in the ectoderm both of the flank and of the dorsal midline and that these two regions have the competence for AER induction. Formation of the AER of the dorsal median ectoderm in the chick embryo is likely to appear as a vestige of the dorsal fin of the ancestors.

Animals↗
PubMed1999

FGF-10 is a growth factor for preadipocytes in white adipose tissue.

FGF-10 is a mesenchymal factor affecting epithelial cells during pattern formation. However, the expression and physiological role of FGF-10 in adults remains to be elucidated. We examined the expression of FGF-10 mRNA in a variety of adult rat tissues, and found to be most abundant in white adipose tissue. In white adipose tissue, FGF-10 mRNA was expressed in preadipocytes but not in mature adipocytes. The expression in white adipose tissue during postnatal development was also examined. The expression level was low at postnatal day 10 (P10). However, FGF-10 mRNA was abundantly detected later on (P28 and P48) when white adipose tissue growth was stimulated. We also examined the activity of recombinant FGF-10 for primary rat preadipocytes. FGF-10 showed significant mitogenic activity for primary preadipocytes, but did not affect the differentiation of preadipocytes. The expression profile of FGF-10 mRNA and the activity of FGF-10 reported here indicate that FGF-10, a unique secreted factor produced in white adipose tissue, acts as a growth factor for preadipocytes in white adipose tissues.

Adipocytes↗
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

Comparison of the right and left ventricle as a systemic ventricle during exercise in patients with congenital heart disease.

BACKGROUND: Few studies have investigated the clinical advantages of surgical correction with the morphologic left ventricle (MLV) instead of the morphologic right ventricle as a systemic ventricle (SV) in patients with congenital heart disease. METHODS: Twenty-four healthy control subjects (group A1), 6 patients with isolated congenitally corrected transposition of the great arteries (TGA) (group A2), 16 patients with TGA who had undergone an arterial switch operation (group B1), 18 patients with TGA who had undergone a venous switch operation (group B2), 9 patients with atrioventricular and ventriculoarterial discordance who had undergone a double switch operation (group C1), and 6 patients with atrioventricular and ventriculoarterial discordance who had undergone a conventional external conduit operation from the MLV to the pulmonary artery (group C2), performed treadmill exercise testing. Their heart rate (HR), oxygen uptake (VO2), and oxygen pulse (O2 pulse), which reflects individual stroke volume, were measured, and contractile function was assessed by echocardiography. RESULTS: The peak HR for the patients after a definitive operation were significantly lower than that in group A1 and was correlated with peak VO2 (r =.67, P <.0001). The peak VO2 and peak O2 pulse for the groups A2 and B2 were significantly lower than those for the groups A1 and B1, respectively. The peak O2 pulse data were strongly correlated with those of peak VO 2 (r = 0.91, P <.0001). The left ventricular ejection fraction was significantly lower in groups B1 and C1 than in group A1 and was correlated with peak VO 2 (r =.50, P <.01). No significant differences in VO2, HR, and O 2 pulse at peak exercise were observed between groups C1 and C2. CONCLUSIONS: Chronotropic incompetence and an impaired response of the stroke volume of the MRV during exercise are partly responsible for the reduced exercise capacity in groups A2 and B2 compared with groups with the MLV as an SV, and the SV function at rest is also related to exercise capacity. Superiority of the double-switch operation compared with the conventional conduit operation was not observed. A longer-term follow-up is necessary before the advantages of these 2 operations can be compared.

Adolescent↗
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

Fgf10 is essential for limb and lung formation.

The interactions between fibroblast growth factors (FGF) and their receptors have important roles in mediating mesenchymal-epithelial cell interactions during embryogenesis. In particular, Fgf10 is predicted to function as a regulator of brain, lung and limb development on the basis of its spatiotemporal expression pattern in the developing embryo. To define the role of Fgf10, we generated Fgf10-deficient mice. Fgf10-/- mice died at birth due to the lack of lung development. Trachea was formed, but subsequent pulmonary branching morphogenesis was disrupted. In addition, mutant mice had complete truncation of the fore- and hindlimbs. In Fgf10-/- embryos, limb bud formation was initiated but outgrowth of the limb buds did not occur; however, formation of the clavicles was not affected. Analysis of the expression of marker genes in the mutant limb buds indicated that the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) did not form. Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation.

Animals↗
PubMed1999

Ventilatory response and arterial blood gases during exercise in children.

To investigate the difference in ventilatory response to exercise between children and young adults, we administered a treadmill progressive exercise test to seven boys (aged 8 to 11 y [group A]) and six male young adults (aged 14 to 21 y [group B]), who had a history of Kawasaki disease without significant coronary arterial lesions, and analyzed their arterial blood gases. There was no significant difference in arterial PO2 or the end-tidal to arterial oxygen tension difference during exercise between groups A and B. The arterial PCO2 (PaCO2) at the ventilatory anaerobic threshold and at peak exercise was significantly lower in group A than in group B (p < 0.05). The arterial to end-tidal carbon dioxide tension difference at peak exercise was significantly greater in group B than in group A (p < 0.05), whereas there was no significant difference at rest or at the ventilatory anaerobic threshold level. The arterial to end-tidal carbon dioxide tension difference at peak exercise was correlated with tidal volume (p < 0.01) and carbon dioxide production (p < 0.05) at peak exercise in all subjects. Although improvement in the physiologic dead space/tidal volume ratio during exercise was smaller in group A than in group B, there was no significant difference in total alveolar ventilation during exercise. However, the total carbon dioxide production during exercise was significantly smaller in group A than in group B. These data suggest that PaCO2 during exercise is better estimated by end-tidal carbon dioxide tension in children than in young adults, that there is a significant difference in change of the PaCO2 during exercise between children and young adults, and that the decrease in PaCO2 in children is related to the mismatch between well-maintained alveolar ventilation and immature metabolic development in the working muscles during moderate-to-severe exercise.

Adolescent↗
PubMed1999

[The effect of milrinone for the shock patients after cardiac surgery].

The effect of milrinone in the 16 postoperative shock patients of cardiovascular surgery was studied. The preoperative hemodynamic status were 12 of cardiogenic shock, 2 cases of chronic heart failure and 2 cases of unstable angina pectoris. The operative procedure were 8 cases of coronary artery bypass grafting, 4 cases of valvular surgery, 2 cases of closure of ventricular septal perforation, 2 cases of Bentall operation and 1 case of ascending aortic replacement. The postoperative hemodynamic status were 15 cases of cardiogenic shock, 10 cases of hemorrhagic shock and 1 case of septic shock. Continuous intravenous infusion of 0.5 microgram/kg/min without initial bolus loading was administered immediately after the entrance of the intensive care unit. Significant increase in the maximum blood pressure 3 hours after the infusion were observed (84 +/- 17 mmHg vs 94 +/- 12, p = 0.033). The maximum blood pressure was increased gradually until 24 hours after the infusion. Significant increase in the peripheral body temperature 3 hours after the infusion were observed (32.5 +/- 2.0 degrees C vs 35.9 +/- 1.1 degrees C, p = 0.001). The difference between the peripheral temperature and the central body temperature diminished until 24 hours after the infusion. No significant change in the central venous pressure, pulmonary arterial pressure, pulmonary and cardiac index wedge pressure were observed. No significant change in the platelet number was observed until 3 days after the infusion. Twenty patients (75%) were discharged. Four hospital deaths included 1 cardiac and 3 septic cause were seen. These data suggest that the administration of milrinone for the shock patients after cardiac surgery showed safe and that the continuous intravenous infusion of 0.5 microgram/kg/min without bolus loading showed effective for the recovery of the peripheral circulation.

Aged↗
PubMed1998

Cardiorespiratory response during exercise in patients with cyanotic congenital heart disease with and without a Fontan operation and in patients with congestive heart failure.

To clarify the different cardiorespiratory response to exercise in patients with congenital heart disease and patients with chronic congestive heart failure, we investigated the effect of a progressive exercise test in 30 patients aged 10 to 24 years, including 9 patients with cyanotic congenital heart disease (group A), 13 patients who had undergone a Fontan operation (group B), and 8 patients with reduced left ventricular function (group C), and 18 healthy controls (group D). There was no difference in peak oxygen uptake among patient groups and all group A, B, and C values were lower than those in group D (P<0.001). Although peak heart rate was lower in patient groups than in group D, heart rate at a given exercise intensity was highest in group C. The oxygen pulse (oxygen uptake divided by heart rate=stroke volume x arterial venous oxygen difference), as an indicator of stroke volume, was lower in patients groups, especially in group C, than in group D. There was no difference in tidal volume between groups A and D, but the respiratory rates at any given exercise intensity were higher in group A than in the other patient groups, thus minute ventilation and the ventilatory equivalent were highest in group A. The increased respiratory rate and low tidal volume in group C resulted in rapid and shallow respiration. There was no difference in exertional symptoms at peak exercise among the groups. In addition to impaired responses of stroke volume during exercise in patients with reduced exercise capacity, there was little limitation of increase in ventilation in group B and excessive ventilation in group A. The present results suggest that relationship between ventilatory and cardiac responses during exercise in patients with cyanotic congenital heart disease with and without a Fontan operation is different from the relationship in patients with chronic congestive heart failure; however, these pathological differences did not influence exertional symptoms.

Adolescent↗
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

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

[Aortic regurgitation caused by the proximal dissecting flap invagination to the left ventricle].

A 68-year-old male with sudden back pain and cardiogenic shock status transferred to our ward. Transthoracic echocardiography revealed that the abnormal round shape string was in the left ventricular outflow tract. The continuity from the staring to the aortic valve was unclear. Intimal flap could not be detected at the level of the ascending aorta. Color Doppler flow imaging showed that the severe AR jet extended into the round string. TEE showed that the intimal tear and flap was seen just above the left subclavian artery. Preoperative diagnosis was acute Stanford type A dissection and acute severe AR due to the inversion of the proximal intimal flap to the left ventricular outflow tract through the aortic valve. At operation, the proximal intimal flap was dissected circumferentially and was cut all the way around 8 cm above the aortic valve ring and was inverted to the left ventricular outflow tract. The aortic valve was preserved because of its normal character after exclusion of the proximal intimal flap. Ascending and arch replacement was carried out. Postoperative TEE and TTE slowed no findings of AR. The patient's postoperative course was uneventful. To our knowledge, this is the first reported case that severe AR caused by the proximal intimal invagination to the left ventricle.

Acute Disease↗
PubMed1998

[Aprotinin and recombinant human erythropoietin reduce the need for homologous blood transfusion in cardiac surgery].

The effects of low dose aprotinin (Trasylol) and preoperative administration of recombinant human erythropoietin (EPO) were evaluated in 144 patients undergoing cardiopulmonary bypass divided into four groups. Group I (n = 43) received a subcutaneous administration of EPO (18,000 U) one week before operation and intraoperative administration of low-dose aprotinin (mean; 1.38 +/- 0.26 x 10(6) kallikrein inactivator units; KIU) from extracorporeal circulation, group II (n = 39) received only preoperative administration of EPO, group III (n = 28) received only intraoperative administration of low-dose aprotinin (mean; 1.46 +/- 0.25 x 10(6) KIU), and group IV (n = 34) were not administered either drug. Compared with group IV, the intraoperative blood loss was significantly lower in group I (p < 0.01), and in group II or III (p < 0.05). The postoperative drainage in 24 hours was significantly lower in groups I and III receiving aprotinin than in the other groups. The mean volume of total homologous blood transfusion and the percentage of cases not requiring a homologous blood transfusion in each group was, respectively, 74 +/- 235 ml and 88.4% in group I, 282 +/- 1289 ml and 87.2% in group II, 414 +/- 584 ml and 60.7% in group III, and 976 +/- 1931 ml and 44.1% in group IV. Significant differences were recognized between group I and group IV (p < 0.05). These findings indicate that when used in combination, both drugs reduce blood loss and the need for a homologous blood transfusion more effectively than either drug alone.

Aged↗
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↗
PubMed1998

Sympathetic reinnervation demonstrated on serial iodine-123-metaiodobenzylguanidine SPECT images after cardiac transplantation.

The transplanted heart is without autonomic nervous control in the early postsurgical period. We present here a case of cardiac transplantation in which 123I-metaiodobenzylguanidine (MIBG) SPECT and an exercise-loading test were used to monitor the sympathetic reinnervation. The distribution of myocardial 123I-MIBG uptake extended with time from 1 to 2 yr after surgery. However, functional improvement, estimated by the heart rate response to exercise, was not discernable during this period. The findings in this case suggest the feasibility of 123I-MIBG SPECT imaging in the serial monitoring of sympathetic reinnervation after transplantation and that scintigraphic evidence of reinnervation precedes functional recovery.

3-Iodobenzylguanidine↗
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

Fibroblasts expressing Sonic hedgehog induce osteoblast differentiation and ectopic bone formation.

We investigated the role of Sonic hedgehog (SHH) in osteoblast differentiation and bone formation. The numbers of ALP-positive cells in the mouse fibroblastic cell line C3H10T1/2 and the mouse osteoblastic cell line MC3T3-E1 were increased by co-culture with chicken fibroblasts transfected with chicken Shh cDNA encoding amino-terminal peptide (Shh-N). The conditioned medium of Shh-N-RCAS-transfected chicken fibroblast cultures also significantly increased ALP activity in both C3H10T1/2 and MC3T3-E1 cells. Intramuscular transplantation of Shh-N-RCAS-transfected chicken fibroblasts into athymic mice induced ectopic bone formation. These results indicate that SHH induces osteoblast differentiation and ectopic bone formation.

3T3 Cells↗