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Biomedical subjects

K Eto

Publications and source records attributed to K Eto.

At least 73 records · Page 4Linked to original sources
PubMed1997

Use of cilostazol, a novel antiplatelet agent, in a post-Palmaz-Schatz stenting regimen.

We evaluated the therapeutic efficacy of cilostazol, a novel potent inhibitor of phosphodiesterase, for the prevention of stent thrombosis following implantation of a Palmaz-Schatz stent guided by angiographic visual estimation alone in 71 patients with 84 lesions. Patients received 81 mg of aspirin 3 times daily and 100 mg of cilostozol twice daily after angiographic confirmation of optimal Palmaz-Schatz stent implantation. Of the 84 vessels stented, 65 (77%) were classified as type B2 or C lesions according to the modified American Heart Association/American College of Cardiology classification, and 51 (61%) were <3.0 mm in diameter. Multiple stents were used in 26 patients (31%). The final balloon inflation pressure was 18.3 +/- 1.5 atm. The balloon-to-vessel ratio was 1.18 +/- 0.16. No patient received heparin or warfarin after the procedure. There were no deaths, Q-wave myocardial infarctions, in- or out-of-hospital stent thrombosis, coronary bypass surgery, or serious side effects such as neutropenia and/or liver dysfunction during the 1-month follow-up period. These results indicate that cilostazol was a safe and effective antiplatelet agent with minimum side effects after Palmaz-Schatz stent implantation.

Adult↗
PubMed1997

Use of synchrotron radiation microangiography to assess development of small collateral arteries in a rat model of hindlimb ischemia.

BACKGROUND: Current methods of angiography cannot provide images of arteries measuring < 200 microns in diameter. We have recently developed a new angiography system that uses monochromatic synchrotron radiation and a high-definition video system with a spatial resolution of 30 microns. In the present study, we applied this microangiography system to visualize small arteries in normal and ischemic rat limbs and investigated the development of collateral arteries. METHODS AND RESULTS: Microangiography was performed in the normal and the ischemic limb 4 weeks after the excision of the femoral artery. In the normal limb, up to the fourth branches of the iliac and/or femoral arteries (diameter < 100 microns) were readily identified. Some of these branches were found to perfuse the distal thigh area. In the ischemic limb, an extensive structural remodeling of the vascular network was observed. Numerous small arteries had developed from the branches of the iliac artery to constitute a fine arterial network, the so-called "midzone," which was composed of linear, normal appearing arteries and those with an undulating, unbranched appearance. CONCLUSIONS: The small collateral artery network was angiographically visualized with a resolution limit < 100 microns. The linear collaterals appeared to result from an opening of preexisting vessels. The undulating, unbranched vessels were not observed in the normal limbs and seemed to be vessels that were newly formed after limb ischemia. Synchrotron radiation microangiography appears to be a powerful means of assessing the development of small collateral arteries, which may help to provide a basis for understanding of the collateral circulation.

Angiography↗
PubMed1997

Apoptotic cell death in neuronal differentiation of P19 EC cells: cell death follows reentry into S phase.

Apoptotic cell death was observed during aggregate culture of the mouse embryonal carcinoma cell line P19 exposed to all-trans retinoic acid (tRA). This finding was confirmed by genomic DNA agarose gel electrophoresis and transmission electron microscopy. Apoptosis was associated with P19 cell neuronal differentiation; alternative causes of cell death, i.e., cavitation-related, cytotoxicity of tRA, or spontaneous cell death were excluded. Analysis by flow cytometry revealed that the apoptosis was likely to occur in multiplying cells that underwent to reentering into S phase. We therefore examined 5-bromo-2'-deoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression and localization in the aggregates by immunofluorescent staining. Although the P19 cells in the aggregates exposed to tRA incorporated BrdU at an equivalent level to those not exposed to tRA, the cells showed diminished PCNA expression and nuclear accumulation. We propose that P19 apoptosis during neuronal differentiation is a model system in which programmed cell death occurs simultaneously with cell division leading to differentiation.

Animals↗
PubMed1997

Microangiographic assessment of collateral vessel formation following direct gene transfer of vascular endothelial growth factor in rats.

OBJECTIVE: The development of collateral microvessels following therapeutic angiogenesis with vascular endothelial growth factor (VEGF) was investigated using a new system of microangiography that employs monochromatic synchrotron radiation (SR) and a high definition video system to visualize arteries with a spatial resolution of 30 microns. METHODS: Ischemia was induced in the hindlimb of 20 rats by excision of the femoral artery, followed by transfection of the plasmid (400 micrograms) encoding VEGF or beta-galactosidase (control) into limb muscles. Microangiography was used to assess the development of collaterals in the ischemic limb four weeks after treatment. RESULTS: Gene transfer of VEGF produced morphologically similar, but significantly more extensive, collateral networks at the microvascular level as compared with the naturally occurring collateral arteries in the control animals (angiographic score: 0.88 +/- 0.08 versus 0.54 +/- 0.05, p < 0.01). No adverse vascular effects such as hemangiomas and/or arteriovenous (AV) fistulae were observed following VEGF treatment. The vasodilator effect of papaverine was evident in relatively large vessels in both groups. At the microvascular level (diameter < 100 microns), however, papaverine induced significant vasodilation in the VEGF-treated animals, and almost no vasodilation in the controls. CONCLUSIONS: SR microangiography allowed us to assess the development of small collateral arteries following VEGF-gene transfer. The information obtained may provide new insights regarding the collateral microcirculation and therapeutic angiogenesis.

Angiography↗
PubMed1997

Cranial anomaly of homozygous rSey rat is associated with a defect in the migration pathway of midbrain crest cells.

Craniofacial development of vertebrates depends largely on neural crest contribution and each subdomain of the crest-derived ectomesenchyme follows its specific genetic control. The rat small eye (rSey) involves a mutation in the Pax-6 gene and the external feature of rSey homozygous embryos exhibits craniofacial defects in ocular and frontonasal regions. In order to identify the mechanism of craniofacial development, we examined the cranial morphology and migration of cephalic crest cells in rSey embryos. The chondrocranial defects of homozygous rSey embryos primarily consisted of spheno-orbital and ethmoidal anomalies. The former defects appeared to be brought about by the lack of the eye. In the ethmoid region, the nasal septum and the derivative of the medial nasal prominence were present, while the rest of the nasal capsule, as well as the nasal and lachrymal bones, were totally absent except for a pair of cartilaginous rods in place of the nasal capsule. This suggests that the primary cranial defect is restricted to the lateral nasal prominence derivatives. Dil labeling revealed the abnormal migration of crest cells specifically from the anterior midbrain to the lateral nasal prominence in homozygous rSey embryos. Pax-6 was not expressed in the crest cells but was strongly expressed in the frontonasal ectoderm. To determine whether or not this migratory defect actually resides in environmental cues, normal midbrain crest cells from wild-type embryos were labeled with Dil and were orthotopically injected into host rSey embryos. Migration of the donor crest cells into the lateral nasal prominence was abnormal in homozygous host embryos, while they migrated normally in wild-type or heterozygous embryos. Therefore, the cranial defects in rSey homozygous embryos are due to inappropriate substrate for crest cell migration towards the lateral nasal prominence, which consistently explains the cranial morphology of homozygous rSey embryos.

Animals↗
PubMed1997

Murine forebrain and midbrain crest cells generate different characteristic derivatives in vitro.

Neural crest (NC) is a transient structure that gives rise to various types of tissues. Many NC cells are pluripotent in the sense that their progeny can generate more than one derivative. However, the potentiality to differentiate into certain derivatives, such as cartilage and bone, seems to be specified with respect to the neuraxial levels at which the NC generates. In order to compare the differentiation potentiality of different regions of head NC, the derivatives of forebrain and midbrain mouse NC have been investigated in vitro using explant cultures of neuroepithelial fragments. From morphology and expression of specific markers, the midbrain crest cultures obviously generated earlier and were greater in number of neuronal cells than were the forebrain ones. Moreover, collagen type II positive cells were detected in the midbrain but not in the forebrain crest cultures. Finally, pigment cells were only observed in the forebrain cultures. The results suggest that the forebrain and midbrain crest cells have a different potentiality to differentiate.

Animals↗
PubMed1997

A chimeric serine/threonine kinase receptor system reveals the potential of multiple type II receptors to cooperate with transforming growth factor-beta type I receptor.

Receptor-type serine/threonine kinases (RSKs) have been organized into two distinct classes known as types I and II on the basis of sequence similarity. However, experiments have shown ligand specificities in the two classes and as a result type I and type II receptors can often bind to a common ligand. The transforming growth factor-beta- (TGF-beta) specific receptors represent such a case, where both type I and II receptors (T beta RI and T beta RII) are observed. Of additional interest is the observation that heteromeric associations of type I and II receptors can also enable signaling. To further elucidate the function of various RSKs, the extracellular domains of both alpha and beta chains from human granulocyte-macrophage colony-stimulating factor receptors were linked to transmembrane cytoplasmic domains of RSKs. Chimeric receptors of human granulocyte-macrophage receptor (hGMR) alpha with T beta RI and hGMR beta with T beta RII were expressed in murine pre-B cell-derived Ba/F3 cells. These chimeras formed heteromeric complexes, transmitted TGF-beta signals, and were down-modulated in response to human granulocyte-macrophage colony-stimulating factor. However, experiments utilizing these chimeric receptors in different combinations revealed that only heteromeric associations of transmembrane cytoplasmic domains mediated signaling and down-modulation. Chimeric receptors with transmembrane cytoplasmic domains of activin receptor type II and bone morphogenetic protein receptor type II also provided signals in conjunction with chimeric T beta RI. As a result, these type II receptors may share a common potential to signal via T beta RI. hGMR-RSK chimeric receptors may be useful tools for the identification and characterization of the divergent signals mediated by individual RSKs.

Activin Receptors, Type I↗
PubMed1997

Pax-6 is involved in the specification of hindbrain motor neuron subtype.

Pax-6 is a member of the vertebrate Pax gene family, which is structurally related to the Drosophila pair-rule gene, paired. In mammals, Pax-6 is expressed in several discrete domains of the developing CNS and has been implicated in neural development, although its precise role remains elusive. We found a novel Small eye rat strain (rSey2) with phenotypes similar to mouse and rat Small eye. Analyses of the Pax-6 gene revealed one base (C) insertion in an exon encoding the region downstream of the paired box of the Pax-6 gene, resulting in generation of truncated protein due to the frame shift. To explore the roles of Pax-6 in neural development, we searched for abnormalities in the nervous system in rSey2 homozygous embryos. rSey2/rSey2 exhibited abnormal development of motor neurons in the hindbrain. The Islet-1-positive motor neurons were generated just ventral to the Pax-6-expressing domain both in the wild-type and mutant embryos. However, two somatic motor (SM) nerves, the abducent and hypoglossal nerves, were missing in homozygous embryos. By retrograde and anterograde labeling, we found no SM-type axonogenesis (ventrally growing) in the mutant postotic hindbrain, though branchiomotor and visceral motor (BM/VM)-type axons (dorsally growing) were observed within the neural tube. To discover whether the identity of these motor neuron subtypes was changed in the mutant, we examined expression of LIM homeobox genes, Islet-1, Islet-2 and Lim-3. At the postotic levels of the hindbrain, SM neurons expressed all the three LIM genes, whereas BM/VM-type neurons were marked by Islet-1 only. In the Pax-6 mutant hindbrain, Islet-2 expression was specifically missing, which resulted in the loss of the cells harboring the postotic hindbrain SM-type LIM code (Islet-1 + Islet-2 + Lim-3). Furthermore, we found that expression of Wnt-7b, which overlapped with Pax-6 in the ventrolateral domain of the neural tube, was also specifically missing in the mutant hindbrain, while it remained intact in the dorsal non-overlapping domain. These results strongly suggest that Pax-6 is involved in the specification of subtypes of hindbrain motor neurons, presumably through the regulation of Islet-2 and Wnt-7b expression.

Animals↗
PubMed1997

Fgfr2 and osteopontin domains in the developing skull vault are mutually exclusive and can be altered by locally applied FGF2.

Mutations in the human fibroblast growth factor receptor type 2 (FGFR2) gene cause craniosynostosis, particularly affecting the coronal suture. We show here that, in the fetal mouse skull vault, Fgfr2 transcripts are most abundant at the periphery of the membrane bones; they are mutually exclusive with those of osteopontin (an early marker of osteogenic differentiation) but coincide with sites of rapid cell proliferation. Fibroblast growth factor type 2 (FGF2) protein, which has a high affinity for the FGFR2 splice variant associated with craniosynostosis, is locally abundant; immunohistochemical detection showed it to be present at low levels in Fgfr2 expression domains and at high levels in differentiated areas. Implantation of FGF2-soaked beads onto the fetal coronal suture by ex utero surgery resulted in ectopic osteopontin expression, encircled by Fgfr2 expression, after 48 hours. We suggest that increased FGF/FGFR signalling in the developing skull, whether due to FGFR2 mutation or to ectopic FGF2, shifts the cell proliferation/differentiation balance towards differentiation by enhancing the normal paracrine down-regulation of Fgfr2.

Animals↗
PubMed1997

Effects of ONO-2235, an aldose reductase inhibitor, on muscarinic receptors and contractile response of the urinary bladder in rats with streptozotocin-induced diabetes.

This study was conducted to evaluate effects of the aldose reductase inhibitor ONO-2235 on the contractile response to acetylcholine of the urinary bladder dome of streptozotocin-induced diabetes mellitus (DM) rats and simultaneously observe the changes in the function and number of muscarinic receptors and the sorbitol content of the bladder. The contractile response to acetylcholine increased 51% in the DM rat bladder dome compared to the normal rats; however, this was attenuated to a 10% increase by administration of 100 mg/kg ONO-2235 for 2 weeks. Treatment with ONO-2235 significantly decreased the specific [3H]quinuclidinyl benzilate binding in DM rats. However there was no significant dose-dependency among the ONO-2235-treated groups. The sorbitol levels of the sciatic nerve and the bladder were higher in the DM rats compared to the control rats; ONO-2235 decreased the level, although it did not completely reverse them to the control level. These results suggest that an aldose reductase inhibitor attenuates the increase of the muscarinic receptor number and normalizes the enhanced contractile response to acetylcholine caused by hyperglycemia and diuresis, probably through suppression of the polyol-pathway in the DM rat bladder dome.

Acetylcholine↗
PubMed1997

Chronic effects of methylmercury in rats. I. Biochemical aspects.

To examine chronic effects of methylmercury (MeHg), male Wistar rats were fed on MeHg-contaminated diet, 0, 1 and 5 ppm Hg, under a restricted feeding schedule of 16 g/rat/day for 6 days a week. Rats were killed at 6-month intervals for examination of Hg accumulation, tissue levels of glutathione, metallothionein and lipid peroxide, as well as anti-oxidative enzyme activities. The survival of the 5 ppm Hg group, 50% of which died by the end of 32nd month of the exposure, was somewhat shorter than control and 1 ppm Hg groups, 50% of which survived for 34 months. Although the rats showed no neurological signs or decreased body weight gain even in 5 ppm Hg-exposed group until the end of the 2nd year, crossing of hind limb was evident after 2.5 years in all three groups. Accordingly, the neurological sign observed here possibly due to aging rather than MeHg toxicity. Tissue Hg levels showed a dose-dependent accumulation except for the kidney, where the highest Hg accumulation was observed among tissues examined. Renal Hg levels in the 1 ppm group showed about 40% of those in the 5 ppm group. Significant effects by MeHg were evident only in the kidney, where glutathione and metallothionein levels increased in both MeHg-exposed groups. However, lipid peroxide levels elevated only in 1 ppm group. Among the antioxidative enzymes examined, the renal glutathione peroxidase was found to be the most labile enzyme against MeHg exposure. Renal dysfunction suggested by increased plasma creatinine levels was also significant in 5 ppm Hg rats at 2 years. Furthermore, anemia which would be caused by reduced erythropoietin production in the kidney was also evident in this group. The present study suggested that the kidney was the most susceptible organ against MeHg toxicity under the present exposure schedule and that the renal dysfunction might at least partly account for the shortened survival in 5 ppm Hg rats.

Administration, Oral↗
PubMed1997

Chronic effects of methylmercury in rats. II. Pathological aspects.

Chronic effects of methylmercury (MeHg) were examined pathologically in male Wistar rats fed on diet containing 0, 1 or 5 ppm Hg (as MeHg) for two years. Organs including the central nervous tissues were examined histopathologically using hematoxylin and eosin (H & E), Klüver-Barrera (KB), PAS or phenol-congo red stains. The peripheral nerve system tissues were also examined, using H & E and trichrome stains. Furthermore, immunoglobulins of renal specimens were demonstrated by direct immunofluorescence microscopy. Localization of mercury in the paraffin-embedded sections of the nervous tissue, kidney, liver, pancreas, spleen and testis was demonstrable by the photoemulsion histochemical method. In the 5 ppm group, mercury was readily detectable in tissues of the rats exposed for one year, one and half years, two years and two and half years. Mercury was detected in the cells of the brain such as neurons, neuroglial cells, and phagocytes, and also in most organs, particularly in the epithelium of renal tubules, liver cells, myocardium, in the macrophages of pancreas, spleen and testis. In the 1 ppm group, mercury was detectable in the epithelium of renal tubules and liver cells. Fibrosis of the glomeruli was found in the rat group given a high dose of methylmercury with all experimental methods. Granular IgG, IgM and C3 deposits were demonstrated in the glomeruli by direct immunofluorescence microscopy. The etiology of the pathological changes of glomeruli was suspected to be autoimmune glomerulopathy due to inorganic mercury filtration for a long time. It was difficult to determine the clinical signs and symptoms and pathological changes in the nervous system in spite of the deposition of mercury in the brain.

Administration, Oral↗
PubMed1997

Mammalian craniofacial embryology in vitro.

Our review demonstrates that the whole embryo culture system established by New and his colleagues, in combination with beneficial fluorescent dye cell-tracing techniques, has greatly contributed to many advancements in the field of mammalian craniofacial embryology, especially with regard to elucidating the developmental behavior of cephalic crest cells. In addition, based on recent results, further combining whole embryo culture with mandibular organ culture methods has allowed us to trace cranial crest cells for a much longer developmental period, i.e., presently up to the cap stage in odontogenesis.

Animals↗
PubMed1997

Effects of cigarette smoke inhalation on plasma diltiazem levels in rats.

A rapid and sensitive method for the assay of plasma diltiazem was developed using a solid-phase extraction technique followed by high-performance liquid chromatography. The effects of cigarette smoke on plasma levels of orally administered diltiazem was investigated in rats. The animals were exposed to cigarette smoke for 10 min using a Hamburg II smoking machine, immediately after oral administration of diltiazem (10 mg/kg). In the nonsmoking nonrestrained rats, plasma diltiazem levels increased rapidly and reached the maximum (7.1 micrograms/kg) 2 h after administration and decreased gradually thereafter. In the nonsmoking restrained rats, plasma diltiazem levels increased rapidly, but showed almost constant levels between 1 h and 8 h after administration. The maximum level (5.4 micrograms/kg) was shown after 2 h. On the other hand, plasma diltiazem levels in the rats exposed to cigarette smoke reached the maximum (4.3 micrograms/kg) after 4 h. These results suggest that absorption of orally administered diltiazem is inhibited and delayed by cigarette smoke.

Animals↗
PubMed1997

[Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy--report of an autopsied Japanese case].

We report a 75-year old Japanese man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). His family had no consanguinous marriage and his grandfather had migraine attacks. His father showed uncontrollable emotion at the age of 59 followed by gait disturbance, disorientation, pseudobulbar palsy and died at the age of 63. The patient had migraine attacks with aura since 10 year-old and showed uncontrolableness of his emotion and gait disturbance at the age of 63 followed by disorientation, urinary incontinence and pseudobulbar palsy, and died from aspiration pneumonia at the age of 75. The postmortem examination revealed an arteriopathy in the cerebral white matter and meningeal vessels and multiple infarctions in the cerebral white matter corpus callosum, basal ganglia, middle cerebellar peduncle and pontine tegmentum. The affected arterial walls showed eosinophilic and periodic acid Schiff (PAS)-positive granules in the media, which were composed of numerous electron dense small granules in varying sizes on electron microscopic examinations. These granules showed complements (Clq, C3, C4)-like immunoreactivity but did not have IgG-, IgM-, IgA-, kappa and lambda chain-, or beta-amyloid-like immunoreactivities. The clinicopathological features in this patient were compatible with those reported as CADASIL in the European countries and this is the first case report of CADASIL in Japanese race.

Aged↗
PubMed1996

Influence of dietary protein levels on the acute toxicity of methylmercury in mice.

The influence of dietary protein levels on the acute toxicity of methylmercury (MeHg) was investigated using C57BL/6N male mice fed either a 24.8% protein diet (normal protein diet, NPD) or a 7.5% protein diet (low protein diet, LPD). When MeHg was administered to each group of mice, all mice died at a medium or high dose (80 or 120 mumol/kg, respectively) within 16 or 7 days, respectively, but not at a low dose (40 mumol/kg) in both dietary groups. Although no difference was observed in the survival rate at a medium dose, NPD-fed mice died earlier despite lower brain Hg than LPD-fed mice at a high dose. Accordingly, death, in our observations, could not be due to neural damage by MeHg. When a high dose of MeHg was administered to mice, plasma aspartate aminotransferase and alanine aminotransferase activities increased in NPD-fed mice but not in LPD-fed mice in spite of similar hepatic Hg levels. Therefore, the higher susceptibility of the liver could be reason for the shorter survival period in NPD-fed mice. Since plasma creatinine increased within 24 h after MeHg administration at a medium or high dose, renal dysfunction could be a major factor in death. The present results suggest that susceptibility to acute MeHg toxicity was higher in NPD-fed mice than in LPD-fed mice, possibly due to the difference in hepatic susceptibility.

Alanine Transaminase↗