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Biomedical subjects

H Kiyama

Publications and source records attributed to H Kiyama.

At least 55 records · Page 3Linked to original sources
PubMed1999

Autologous blood donation with recombinant human erythropoietin in anemic patients.

BACKGROUND: Various blood management strategies can be used to reduce the need for allogeneic blood in cardiac surgery. In anemic patients, however, avoidance of allogeneic blood transfusion is difficult to achieve. This study was performed to assess the safety and effectiveness of preoperative blood collection using recombinant human erythropoietin (rHuEPO) for reducing the exposure to allogeneic blood in anemic patients. METHODS: Thirty-two anemic patients undergoing cardiac surgery at our hospital between January 1994 and October 1997 were divided into two groups according to preoperative strategies: 3-week treatment with rHuEPO and blood donation (group 1, n = 16) or iron supplementation alone (group 2, n = 16). RESULTS: There were no statistically significant differences between the two groups in patients' characteristics and surgical data. The number of reticulocytes was increased at just before surgery in group 1, whereas group 2 showed no significant increase. The estimated hemoglobin increases in group 1 were higher at 7 days and just before surgery. The mean number of required allogeneic blood for patients during surgery was 0.59 +/- 1.12 U in group 1 and 5.01 +/- 2.63 U in group 2. In 75% of group 1 patients, allogeneic blood transfusion was successfully avoided, whereas all patients in group 2 received allogeneic blood. CONCLUSIONS: This study suggests that the combination of rHuEPO administration and autologous blood donation can reduce the need for allogeneic blood in anemic patients.

Aged↗
PubMed1999

Dimethylarginine dimethylaminohydrolase (DDAH) as a nerve-injury-associated molecule: mRNA localization in the rat brain and its coincident up-regulation with neuronal NO synthase (nNOS) in axotomized motoneurons.

As part of a project to identify genes up-regulated by injury of the motor neuron, a clone encoding dimethylarginine dimethylaminohydrolase (DDAH) was isolated. This enzyme is known to metabolize methylarginines, which are endogenous inhibitors of NOS activity. DDAH may therefore contribute to the control of NO synthesis. The present study demonstrated that both DDAH and nNOS mRNAs are up-regulated after axotomy in injured hypoglossal motor neurons. The profile of DDAH mRNA up-regulation in the injured hypoglossal motor neurons paralleled that of NADPH diaphorase staining. While the expression of both DDAH and nNOS was upregulated in motor neurons following nerve injury, the normal distribution of DDAH and nNOS mRNAs in the noninjured central nervous system were distinctly different. We speculate that both genes are involved in the upregulation of NO production following nerve transection, although the role of NO in the process of nerve regeneration is so far unknown.

Amidohydrolases↗
PubMed1999

Insulin-induced hypoglycemia activates a chemokinergic neuronal pathway in the hypothalamo-pituitary system.

Recently, we found the presence of cytokine-induced neutrophil chemoattractant (CINC) neuronal pathway in the hypothalamo-pituitary system. This observation prompted us to investigate the effect of insulin-induced hypoglycemia on CINC neuronal pathway in the hypothalamo-pituitary system. An insulin injection decreased the plasma glucose level, which followed a prompt rise in plasma ACTH level and an increase in serum CINC level. Before the insulin injection, the signal for CINCmRNA was undetectable in the paraventricular hypothalamic nucleus (PVN). The hypoglycemic challenge induced strong hybridization signals of CINC mRNA in the parvocellular and magnocellular subdivision of the PVN within 30 min, and reached the peak within 3 h. No change was observed in the supraoptic nucleus after the hypoglycemic challenge. These studies demonstrate the presence of a hypoglycemia-sensitive chemokinergic neuronal pathway in the hypothalamo-neurohypophysial system and this newly described pathway will provide novel information for understanding pathophysiology of hypoglycemia.

Acute Disease↗
PubMed1999

[Aortic valve operations through an upper partial sternotomy].

The median sternotomy has been accepted as the most common approach to the heart, because this approach is easily opened and closed, and easy access to the entire heart is possible. Following the pioneering work by Cosgrove and colleagues of using a parasternal incision for aortic and mitral valve operations, several reports suggested that modified minimal access procedures are likely to be associated with reduced postoperative discomfort and faster recovery. Since July 1997, we have used an upper partial sternotomy and a limited skin incision for isolated aortic valve replacement (AVR) at our hospital. To demonstrate the benefits of this approach, we compared 14 AVR operations using our minimal access incision (group M) with 19 patients undergoing isolated AVR using a conventional sternotomy (group F). In the minimal access group of patients, a small skin incision was made from the second intercostal space to the fourth rib. The pectralis major and intercostal muscle was freed from the sternum, and then a transverse half sternotomy was made in the fourth intercostal space using a striker without injury to the right internal mammary artery. A median partial sternotomy from the supersternal notch to the level of the fourth intercostal space. Cardiopulmonary bypass was connected through the same access site to avoid cannulation of both groins. Conversion to median sternotomy was not necessary in any patient including reexploration for postoperative bleeding. There was no operative mortality, stroke, aortic dissection and perivalvular leaks due to technical factors. In group F, wound infection occurred in 1 patient. One patient in group M required reoperation to control postoperative bleeding. Although mean duration of operation, cardiopulmonary bypass, and cross clamp time in group M was not prolonged, the initiation of cardiopulmonary bypass and aortic crossclamp was delayed by difficulties of cannulations. The distance between the transverse sternotomy (lower edge of divided sternum) and the midpoint of aortic valve annulus was correlated with mean duration of cardiopulmonary bypass and cross clamp time. Our experience demonstrates that isolated AVR through an upper partial sternotomy allows the same quality operations as the full sternotomy, although more clinical experience is required to clarify the benefits of this approach. Excellent exposure of the aortic valve through a partial sternotomy may be attained, if an adequate approach can be selected by the position of aortic valve.

Aortic Valve↗
PubMed1999

[Double chambered right ventricle in a 62-year-old female: a surgical case report].

A 62-year-old female was admitted with a chief complaint of transient syncope on exertion. Angiography in right ventricle revealed a defect caused by an anomalous muscle bundle and a pressure gradient of 151 mmHg was observed between the two chambers by cardiac catheterization. Resection of the anomalouse muscle bundle was undertaken using a lower median sternotomy starting at the 2nd intercostal space level and through the outflow tract right ventriculotomy. Patch plasty was also undertaken in the outflow tract. Post-operative course was uneventful and pressure gradient had disappeared at the post-operative catheterization. A rare case of DCRV in a 62-year-old patient with a pressure gradient of 151 mmHg in the right ventricle was reported.

Cardiac Surgical Procedures↗
PubMed1999

[Implication of growth factor receptor signaling for axotomized motor neuron survival after nerve injury].

Motor neurons are able to survive even after nerve injury. In order to reveal the molecular basis underlying this survival mechanism, we carried out gene screening using Differential Display PCR method and a cDNA library derived from rat injured hypoglossal nuclei. This gene hunting provided us with some of the parts of the molecular mechanism for nerve regeneration, among which intracellular signaling molecules, in particular downstream growth factor receptors, seemed very important. We therefore examined the significance of the molecules by using adenovirus mediated gene transfer system, and concluded that PI3K-Akt pathway could be one of the important pathways by which injured motor neurons survive and regenerate.

Adenoviridae↗
PubMed1999

Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons.

Emerging data indicate that growth factors such as insulin-like growth factor-1 (IGF-1) prevent neuronal death due to nitric oxide (NO) toxicity. On the other hand, growth factors can promote cell survival by acting on phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, serine-threonine kinase Akt, in various types of cells. Here, we examined the mechanism by which IGF-1 inhibits neuronal apoptosis induced by NO in primary hippocampal neurons. IGF-1 was capable of preventing apoptosis and caspase-3-like activation induced by a NO donor, sodium nitroprusside or 3-morpholin-osydnonimine. Incubation of neurons with a P13-kinase inhibitor, wortmannin or LY294002, blocked the effects of IGF-1 on NO-induced neurotoxicity and caspase-3-like activation. In addition, the P13-kinase inhibitors blocked the effect of IGF-1 on down-regulation in Bcl-2 and upregulation in Bax expression induced by NO. Adenovirus-mediated overexpression of the activated form of Akt significantly inhibited NO-induced cell death, caspase-3-like activation, and changes in Bcl-2 and Bax expression. Moreover, expression of the kinase-defective form of Akt almost completely blocked the effects of IGF-1. These findings suggest that activation of Akt is necessary and sufficient for the effect of IGF-1 and is capable of preventing NO-induced apoptosis by modulating the NO-induced changes in Bcl-2 and Bax expression.

Adenoviridae↗
PubMed1998

A sequence-specific splicing activator, tra2beta, is up-regulated in response to nerve injury.

Tra2beta is the first mammalian protein which is proved to activate mRNA splicing in sequence-specific manner. Following hypoglossal nerve injury, the expression of Tra2beta mRNA was elevated in injured motoneurons transiently. The up-regulation of Tra2beta mRNA was observed from post-operative day 3 to 21. In addition to the nerve injury in PNS, a brain lesion in CNS also enhanced the expression of Tra2beta mRNA. The present study could be the first observation showing that an expression of the sequence-specific splicing activator is enhanced in neuronal cells in response to nerve injury, and indicates that Tra2beta may participate in the control of injury-specific splicing patterns in order to express molecules which are necessary for regeneration.

Animals↗
PubMed1998

Up-regulation of thioredoxin expression in motor neurons after nerve injury.

A substantial up-regulation of thioredoxin, a dithiol/disulfide oxido-reductase, in adult rat motoneurons following hypoglossal nerve axotomy, was demonstrated by using both in situ hybridization and immunohistochemistry. Although thioredoxin is normally accumulated more in the nucleus of a motoneuron rather than in the cytoplasm, a dramatic increase of thioredoxin in the cytoplasmic region after nerve injury was observed. The up-regulation of mRNA lasted more than 9 weeks, whereas, the detectable up-regulation of protein was observed for more than 5 weeks.

Animals↗
PubMed1998

Unilateral labyrinthectomy downregulates glutamate receptor delta-2 expression in the rat vestibulocerebellum.

The differential display method was applied to identify genes expression of which is altered in the flocculus after unilateral labyrinthectomy (UL). Total RNA from sham operated and labyrinthectomized rat flocculi was isolated, amplified by PCR using an arbitrary primer set and separated by electrophoresis on a polyacrylamide gel. PCR products the amounts of which were significantly lower in samples from labyrinthectomized animals than those from controls, were cut out of the gel and sequenced. One of the cDNA fragments showed 100% nucleotide sequence identity to the rat glutamate receptor (GluR) delta-2 subunit mRNA. In situ hybridization autoradiography showed that GluR delta-2 mRNA expression was intensely located to the floccular Purkinje cell layers. Furthermore, northern blot analysis showed that the delta-2 mRNA expression was decreased for at least two days after UL in accordance with diminishing UL-induced behavioral deficits. Therefore, it is suggested that the downregulation of delta-2 mRNA is involved in vestibular compensation. UL-induced spontaneous nystagmus (SN) was then examined in GluR delta-2 mutant mice. The frequency of SN in mutant mice was significantly more than that in wild mice until 12 h after UL. GluR delta-2-associated synaptic efficacy may be changed for the induction of vestibular compensation at the initial stage.

Animals↗
PubMed1998

Trapdoor thoracotomy as a surgical approach for aortic arch aneurysm.

Since 1991 ten patients, 9 male and 1 female, with aortic arch aneurysm underwent surgical therapy with trapdoor thoracotomy. The mean age was 67.4 +/- 9.1 (standard deviation) years at operation. In addition to the aortic arch repair, we also performed seven descending aortic replacements. We performed one partial arch replacement, one total arch replacement, and one aneurysmorrhaphy and wrapping of the aortic arch aneurysm. We experienced 1 case of paraplegia, no hospital death, and no long-term mortality.

Aged↗
PubMed1998

Alternative expression of Shc family members in nerve-injured motoneurons.

Expression of Shc family protein (Shc/ShcA, SCK/ShcB and N-Shc/ShcC) and Grb2 mRNAs in the hypoglossal motoneurons after axotomy was examined by in situ hybridization. In normal hypoglossal motor neurons, N-Shc mRNA was expressed predominantly, whereas the Shc mRNA level is very low. Rat hypoglossal nerve injury reversed the expressions of these two molecules in hypoglossal motoneurons. Shc mRNA expression was up-regulated markedly whereas N-Shc was down-regulated after nerve injury. Expression levels of SCK, another Shc family member, and Grb2 were unaffected by nerve injury. These results suggest that, whereas the N-Shc-mediated pathway dominates under normal conditions, an alternative Shc-mediated pathway is utilized in the event of nerve injury. By changing the expression of the Shc family members, the signaling pathway can be altered and various responses induced for nerve regeneration.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Enhanced expression of 14-3-3 family members in injured motoneurons.

An increase in 14-3-3 mRNA expression after hypoglossal nerve injury was demonstrated by RNA finger printing using the arbitrary primed polymerase chain reaction (RAP-PCR). RAP-PCR was carried out to compare differences in mRNA expression between axotomized (6 h after the transection) and normal hypoglossal nuclei in mice. The expression of several gene fragments was increased after nerve injury; one fragment was identified as 14-3-3 which is an activator of Raf-1. Since a family of 14-3-3 genes are identified in the rat, we examined the expression of five members of the rat 14-3-3 family after injury (beta, gamma, zeta, eta and theta). Among these family members, a substantial up-regulation in mRNA expression was observed for the zeta and θ forms. Subsequent emulsion autoradiography of hybridization tissue sections revealed an increase in zeta and theta mRNA in injured motoneurons. Since 14-3-3 has the ability to dimerize and activate Raf-1, the up-regulation of 14-3-3 expression would be expected to facilitate the Ras-Erk signal pathway by Raf-1 activation. Our previous results have demonstrated that Shc, Erk1 and Mek1 mRNAs are up-regulated during nerve regeneration, whereas PKA which inhibits the Ras-Erk pathway via Raf-1 was down-regulated. Taken together, the present results suggest that enhancement in expression of molecules involved in the Ras-Erk signaling is required for peripheral nerve regeneration.

14-3-3 Proteins↗
PubMed1998

Enhancement of extracellular glutamate scavenge system in injured motoneurons.

An increase in glutamine synthetase (GS) mRNA expression after peripheral motor nerve injury was demonstrated by differential display PCR using single arbitrary primer coupled with in situ hybridization screening called in situ display. Differential display PCR was carried out to compare differences in mRNA expression between axotomized (6 h after the transection) and normal hypoglossal nuclei in mice. Several gene fragments were increased after nerve injury; one was identified as GS. Subsequent emulsion autoradiography of hybridization tissue sections revealed that the increase in GS mRNA was observed in injured motoneurons. As GS is a key enzyme participating in the metabolism of the major excitatory neurotransmitter glutamate, we examined the significance of increased GS expression on glutamate-uptake kinetics. GS-transfected human embryonic kidney cells showed an up-regulation in glutamate-uptake kinetics. Therefore, newly expressed GS together with an increased expression of the neuronal glutamate transporter EAAC1 in the injured motoneurons accelerates glutamate uptake. The present results may suggest that the glutamate-uptake system involving the neuronal glutamate transporter and GS in injured neurons is enhanced so as to provide resistance against neurotoxic glutamate accumulation during the early process of nerve regeneration.

Animals↗
PubMed1998

An implication of protein phosphatase 2A-beta in the rat flocculus for lesion-induced vestibular plasticity.

The differential display method was applied to identify genes, the expression of which is up-regulated in the cerebellar flocculus after unilateral labyrinthectomy (UL). Total RNA from sham-operated and labyrinthectomized rat flocculi was isolated, amplified by polymerase chain reaction (PCR) using a single arbitrary primer and separated by electrophoresis on a polyacrylamide gel. PCR products in amounts significantly higher in samples from labyrinthectomized animals than in those from controls were cut out of the gel and sequenced. One of the cDNA fragments showed 100% nucleotide sequence identity to the rat protein phosphatase 2A (PP2A)-beta catalytic subunit mRNA. In situ hybridization histochemistry and Northern blot analysis showed that PP2A-beta mRNA expression was intensely localized to the floccular Purkinje cell layer and up-regulated with a maximum increase within 2 days after UL. In labyrinthectomized rats, UL-induced nystagmus gradually disappeared within 3 days after UL. However, in animals with continuous floccular infusion of okadaic acid, a potent inhibitor of PP2A, UL-induced nystagmus lasted significantly longer. All these findings suggest that up-regulation of PP2A-beta mRNA in floccular Purkinje cells after UL is involved in lesion-induced vestibular plasticity. So far, various kinds of neural plasticity-associated molecules have been investigated mainly by slice in vitro studies. This paper indicates that differential display is the feasible molecular biological in vivo method for an investigation about the mechanism of neural plasticity.

Animals↗
PubMed1998

Molecular mechanisms of vestibular compensation in the central vestibular system--review.

Vestibular compensation consists of two stages: the inhibition of the contralesional medial vestibular nucleus (contra-MVe) activities at the acute stage after unilateral labyrinthectomy (UL) and the recovery and maintenance of the ipsilesional MVe (ipsi-MVe) spontaneous activities at the chronic stage after UL. In this paper, we reviewed molecular mechanisms of vestibular compensation in the central vestibular system using several morphological and pharmacological approaches in rats. Based on our examinations, we propose the following hypotheses: i) at the acute stage after UL, the activated neurons in the ipsi-MVe project their axons into the flocculus to inhibit the contra-MVe neurons via the NMDA receptor, nitric oxide (NO) and/or GABA-mediated signalling, resulting in the restoration of balance between intervestibular nuclear activities. ii) At the chronic stage after UL, the flocculus depresses the inhibitory effects on the ipsi-MVe neurons via protein phosphatase 2A (PP2A) beta, protein kinase C (PKC) and glutamate receptor (GluR) delta-2, to help the recovery and maintenance of ipsi-MVe activities.

Animals↗
PubMed1998

[A case of progressive right coronary ostial stenosis after Carrel patch method using gelatin-resorcin-formalin glue].

A 31-year-old man with type A chronic aortic dissection associated with annuloaortic ectasia underwent the concomitant graft replacement of the total aortic root and the transverse aortic arch. The two coronary arteries were reconstructed using the Carrel patch method. The false lumen of right coronary artery was closed by injection of GRF glue into the dissected space and compressing the dissected layers. Postoperative course was uneventful, and the patient has returned to normal daily life 2 months after surgery. Remarkable progression of the right coronary artery ostial stenosis was observed by coronary angiography 6 months after surgery. The remarkable progression of stenosis may occur in association with injection of GRF glue into the dissected space, although the exact etiology of the progressive stenosis remains obscure.

Adult↗