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Nobuo Hashimoto

Publications and source records attributed to Nobuo Hashimoto.

At least 73 records · Page 4Linked to original sources
PubMed2005

Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain.

OBJECT: Cell replacement therapy including the use of embryonic stem cells (ESCs) may represent a novel treatment for damage from stroke. In this study, the authors transplanted neural progenitor cells (NPCs) derived from ESCs into ischemic brain and analyzed their survival and differentiation. METHODS: Multipotential NPCs were generated from ESCs by using the stromal cell-derived inducing activity method. These cells could differentiate in vitro into neurons, glia, and oligodendrocytes, thus revealing them to be neural stem cells. The NPCs were then transplanted into ischemic brain. At 2 weeks postischemia, the transplanted cells occupied 18.8 +/-2.5% of the hemispheric area; by 4 weeks postischemia, 26.5 +/- 4% of the hemisphere. At 4 weeks after transplantation, green fluorescent protein (GFP)-positive transplanted cells showed mature neuronal morphological features. The authors also investigated the expression of differentiation markers and various neurotransmitters. Transplanted cells were immunopositive for neuronal nuclei, beta-tubulin-III, and glial fibrillary acidic protein. Of the GFP-positive cells, 33.3 +/-11.5% were positive for glutamate decarboxylase, 13.3 +/- 5.8% for glutamate, 2.1 +/- 2.5% for tyrosine hydroxylase, 1.8 +/- 2% for serotonin, and 0.4 +/- 0.2% for choline acetyltransferase. CONCLUSIONS: The authors confirmed the survival and differentiation of ESC-derived NPCs transplanted into the ischemic brain. Surviving transplanted cells expressed several neural markers and neurotransmitters. These findings indicate that these cells can function in the brain.

Animals↗
PubMed2005

Diaphragmatic paralysis caused by cervical spondylosis. Case report.

The authors describe a rare case of diaphragmatic paralysis caused by cervical spondylosis. A 64-year-old man presented with dyspnea as well as cervical radicular pain and left-sided upper-extremity motor weakness. Chest radiography revealed elevation of both sides of the diaphragm. All symptoms were ameliorated immediately after cervical laminoplasty, and spirometry revealed improvement of ventilatory function 6 months after surgery. Cervical spondylosis should be considered a factor that can cause respiratory dysfunction.

Cervical Vertebrae↗
PubMed2005

Accelerated embolization healing of aneurysms by polyethylene terephthalate coils seeded with autologous fibroblasts.

OBJECTIVE: The objective of this study was to develop a therapeutic system of aneurysm embolization on the basis of organization of fibrous tissue. The healing process of aneurysms by means of polyethylene terephthalate (PET) fiber coils seeded with autologous fibroblasts was evaluated. METHODS: The aneurysm was prepared at the common carotid artery of 42 rabbits by end-to-side anastomosis of the jugular vein pouch. PET fiber coils seeded with or without autologous fibroblasts were applied to the aneurysm. Assessment of the tissue appearance and histological examination were performed 3 and 5 weeks after application to evaluate the area embolized by fibrous organization in the aneurysm and the neointima formation at the aneurysm orifice. RESULTS: An agitated seeding method enabled autologous fibroblasts to attach and proliferate homogeneously on the PET fiber coil. In contrast to the PET fiber coil, the PET fiber coil seeded with autologous fibroblasts accelerated the organization of fibrous tissue in the aneurysm and time to achieve aneurysm embolization. The aneurysm orifice was closed with neointima formed. The aneurysm was histologically embolized with newly formed fibrous tissue, and the area embolized was significantly larger than that of nontreated and the PET fiber coil-treated groups. The orifice was completely covered with endothelial cells. CONCLUSION: The PET fiber coil seeded with autologous fibroblasts is a promising tool for healing aneurysms using embolization therapy by tissue organization.

Balloon Occlusion↗
PubMed2005

[Treatment with phosphate binder (sevelamer hydrochloride, calcium carbonate) based on PTH].

When sevelamer hydrochloride is used as a phosphate binder instead of the more common calcium carbonate, the PTH rises. This has been observed in many cases and makes it more difficult for practical use. However, considering the calcium load, the excessive dosing of calcium carbonate must be avoided. With that in mind, we divided the i-PTH in groups of 100 pg/mL and tested the changes in i-PTH value, P value, the adjusted Ca value, and the product of Ca and P before and after a dosage of sevelamer hydrochloride. When the average i-PTH was under 100mg/mL 6 months before dosing, the sevelamer hydrochloride single dosage group showed an early rise in i-PTH after dosing, maintaining a higher level than the calcium carbonate combined dosage group. Therefore, it was concluded that the use of sevelamer hydrochloride alone as a phosphate binder is best. On the other hand, the group with an average i-PTH over 100 pg/mL 6 months before dosing showed a rise of i-PTH that went over the K/DOQI guideline with a single dosing of sevelamer hydrochloride. Therefore, we concluded that using both sevelamer hydrochloride and calcium carbonate for phosphate binder is best.

Aged↗
PubMed2005

[Defining the role of sevelamer chloride as a therapeutic agent for management of phosphate in patient with hemodialysis].

It has been about 18 months after the commercial release of sevelamer hydrochloride. I examined the phosphorus management in patient with hemodialysis with the use sevelamer hydrochloride. The phosphorus reduction of sevelamer hydrochloride was weaker than the precipitated calcium carbonate. Patients on artificial dialysis must undergo dietary therapy for the sevelamer hydrochloride to be effective. However, by switching from precipitated calcium carbonate to sevelamer hydrochloride, the calcium level dropped, and as a result the intact PTH rose. It was possible to subdue the rise of intact PTH with vitamin D. The usefulness of vitamin D dramatically increased with the decrease and the eventual cancellation of precipitated calcium carbonate. Furthermore, the calcium load lightened and the product of calcium and phosphorus decreased. At this point, I do not expect substantial phosphorus reduction from sevelamer hydrochloride. It must be recognized that the basis of phosphorus management is proper diet. Only with that can sevelamer hydrochloride be used to its fullest potential.

Aged↗
PubMed2005

[Relationship between serum calcium level and PTH concentration proved with sevelamer hydrochloride].

About a dialysis patient's calcium-phosphate (Ca.P) metabolism, in general good control is obtained by use of sevelamer hydrochloride. As for this, what is significantly depended on not only lower P concentration but also lower Ca concentration by the change to sevelamer hydrochloride from calcium carbonate. However, by one side, much rises of i-PTH are observed by most patients with change to sevelamer hydrochloride. In this examination, Deltai-PTH was intentionally correlated with Delta calcium concentration but there was no correlation in i-PTH and Ca concentration.

Calcium↗
PubMed2004

Ectopic posterior pituitary high signal in preoperative and postoperative macroadenomas: dynamic MR imaging.

BACKGROUND AND PURPOSE: In patients with macroadenoma, posterior pituitary high signal (PPHS) on T1-weighted magnetic resonance (MR) imaging is sometimes observed in an ectopic location. The present study compared incidences of ectopic PPHS before and after macroadenoma surgery using MR imaging, including dynamic MR imaging to ascertain whether this ectopic change is irreversible. MATERIALS AND METHODS: MR imaging was performed preoperatively in 111 cases of macroadenoma, and then repeated more than 1-year postoperatively in 47 patients. Enhancement of PPHS was assessed using dynamic MR imaging. Areas of enhanced hyperintensity were considered true PPHS, and the relationship between presence and location of true PPHS and adenoma volume was analyzed. Moreover, changes in the presence and location of true PPHS were ascertained among the patients who underwent postoperative follow-up MR imaging. RESULTS: Preoperatively, PPHS was seen only in the normal location in 29 patients (Group A: 26.1%). High signal was detected only in an ectopic location in 58 patients, and early enhancement of this ectopic high signal was confirmed by dynamic MR imaging in 56 patients (Group B: 50.5%). No PPHS was observed in 24 patients (Group C: 21.6%). Adenoma volume was significantly greater for Group B than for Group A (p<0.001). Among the Group B patients who underwent MR imaging postoperatively (n=31), the location of PPHS was not changed, except for two patients in whom PPHS was absent. Postoperatively, PPHS was not observed in the normal location in any patient in the Group B. CONCLUSIONS: Greater volume of adenoma is associated with a higher incidence of ectopic PPHS, and the ectopic change is irreversible.

Adenoma↗
PubMed2004

Genome-wide scan for Japanese familial intracranial aneurysms: linkage to several chromosomal regions.

BACKGROUND: Genetic factors have an important role in the pathogenesis of intracranial aneurysm (IA). The results of previous studies have suggested several loci. METHODS AND RESULTS: From 29 IA families with > or =3 individuals affected by IA, we used nonparametric (model-free) methods for linkage analyses, using GENEHUNTER and Merlin software. Genome-wide linkage analyses revealed 3 regions on chromosomes 17cen (maximum nonparametric logarithm of the odds score [MNS] = 3.00, nominal P=0.001), 19q13 (MNS=2.15, nominal P=0.020), and Xp22 (MNS=2.16, nominal P=0.019). We tested 4 candidate genes in these regions: the microfibril-associated protein 4 gene (MFAP4) and the promoter polymorphism of the inducible nitric oxide synthase gene (NOS2A) on chromosome 17cen, the epsilon genotypes of the apolipoprotein E gene (APOE) on chromosome 19q13, and the angiotensin I converting enzyme 2 gene (ACE2) on chromosome Xp22. Associations of their polymorphisms with IA were evaluated by a case-control study (100 cases: 29 probands from IA families and 71 unrelated subjects with IAs, 100 unrelated control subjects [unaffected members with IAs and absence of family history of IAs]). However, the case-control study showed that none of the polymorphisms of the examined genes had associations with IA. CONCLUSIONS: A genome-wide scan in 29 Japanese families with a high degree of familial clustering revealed 1 suggestive linkage region on chromosome 17cen and 2 potentially interesting regions on chromosomes 19q13 and Xp22. These regions were consistent with previous findings in various populations.

Aged↗
PubMed2004

Effects of phosphoinositide 3-kinase on endothelin-1-induced activation of voltage-independent Ca2+ channels and vasoconstriction.

We recently demonstrated that endothelin-1 (ET-1) activates two types of Ca(2+)-permeable nonselective cation channel (designated NSCC-1 and NSCC-2) and a store-operated Ca(2+) channel (SOCC) in rabbit basilar artery (BA) vascular smooth muscle cells (VSMCs). In this study, we investigated the effects of phosphoinositide 3-kinase (PI3K) on ET-1-induced activation of these channels and BA contraction by using PI3K inhibitors, wortmannin and LY 249002. To determine which Ca(2+) channels are activated via PI3K, monitoring of intracellular Ca(2+) concentration was performed. Role of PI3K in ET-1-induced vasoconstriction was examined by tension study using rabbit BA rings. Only NSCC-1 was activated by ET-1 in wortmannin- or LY 294002-pretreated VSMCs. In contrast, addition of these drugs after ET-1 stimulation did not suppress Ca(2+) influx. Wortmannin inhibited the ET-1-induced contraction of rabbit BA rings that depends on the Ca(2+) influx through NSCC-2 and SOCC. The IC(50) values of wortmannin for the ET-1-induced Ca(2+) influx and vasoconstriction were similar to those for the ET-1-induced PI3K activation. These results indicate that (1) NSCC-2 and SOCC are stimulated by ET-1 via PI3K-dependent cascade, whereas NSCC-1 is stimulated via PI3K-independent cascade; (2) PI3K is required for the activation of the Ca(2+) entry, but not for its maintenance; and (3) PI3K is involved in the ET-1-induced contraction of rabbit BA rings that depends on the extracellular Ca(2+) influx through SOCC and NSCC-2.

Acetamides↗
PubMed2004

Overexpression of RFT induces G1-S arrest and apoptosis via p53/p21(Waf1) pathway in glioma cell.

The regulator of fibroblast growth factor 2 (FGF-2) transcription (RFT) has been reported to be a transcriptional repressor of FGF-2 and induce glioma cell death by its overexpression. Here we report that RFT regulates cell cycle as well as apoptosis by a novel mechanism. RFT expressed in some glioma cell lines, U138MG and T98G, but neither in U87MG nor U251MG. Overexpressed RFT-induced apoptosis in U87MG and U138MG with functioning-type p53 but neither in U251MG nor T98G with non-functioning-type p53. Administration of FGF-2 failed to prevent RFT-induced apoptosis. Overexpression of RFT caused G1-S arrest and upregulated both the phosphorylation of p53 at Ser-15 and the expression level of p21(Waf1). Furthermore, RNAi knockdown of p53 abolished RFT-induced apoptosis in U87MG. Taken together, our results support that RFT regulates G1-S transition and apoptosis via p53/p21(Waf1) pathway.

Apoptosis↗
PubMed2004

Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane.

Klotho mutant mice exhibit a set of phenotypes resembling human ageing. Although the function of Klotho remains unclear, mediation of its pleiotropic functions by putative humoral factor(s) has been presumed. Newly established antibodies against Klotho allowed the detection of secreted Klotho, a candidate for the putative humoral factor, in sera and cerebrospinal fluid. Surprisingly the secreted Klotho was 130 kDa, in contrast to the 70 kDa predicted form from klotho gene transcripts. The secreted as well as the membrane-bound Klotho proteins were suggested to form oligomerized complex. These results delineate post-translation processing of Klotho and possible regulatory mechanisms for secretion of Klotho in vivo.

Alternative Splicing↗
PubMed2004

Neural precursor cells derived from human embryonic brain retain regional specificity.

Recent studies have revealed that neural precursor cells can be expanded not only from the subventricular zone and hippocampus but also from other regions of the human embryonic brain. To determine the regional differences of these precursor cells, we divided the brain of a 9-week-old human embryo into four parts, i.e., telencephalon, diencephalon, mesencephalon, and rhombencephalon. All cultures of the tissues yielded neurospheres, and these spheres gave rise to neurons, astrocytes, and oligodendrocytes. An analysis of clonal populations revealed that these precursor cells were multipotent, and two region-specific differences in neural precursor cells were revealed: 1) The precursor cells from the rostral part of the brain tended to proliferate faster than those from the caudal part, and 2) the precursor cells from the diencephalon and mesencephalon gave rise to more tyrosine hydoxylase (TH)-positive neurons than those from the telencephalon and rhombencephalon. When 50-day-cultured spheres were caused to differentiate, the percentage of TH-positive cells per total cell population was 1.2% for diencephalic and mesencephalic precursors, whereas it was 0.4% for telencephalic and rhombencephalic ones. Furthermore, the TH-positive cells from diencephalic and mesencephalic precursors were large, multipolar, and gamma-aminobutyric acid (GABA)-negative, which suggested that these cells were midbrain dopaminergic neurons. In contrast, TH-positive cells from telencephalic and rhombencephalic precursors were small, bipolar, and GABA-positive. These results suggest that human neural precursor cells might have the potential to differentiate into a variety of cells but retain regional specificity.

Animals↗
PubMed2004

Human eye fields in the frontal lobe as studied by epicortical recording of movement-related cortical potentials.

We studied the generator location of premovement subcomponents of movement-related cortical potentials (MRCPs) [Bereitschaftspotential (BP), negative slope (NS') and motor potential (MP)] associated with voluntary, self-paced horizontal saccade in the human frontal lobe. Self-paced horizontal saccade, wrist (or middle finger) extension and foot dorsiflexion were employed in 10 patients (lateral surface of the frontal lobe in seven and mesial in three) as part of the presurgical evaluation, and data of five patients (lateral in four and mesial in three) were used in the final analysis. On the lateral frontal lobe, the maximum BP, NS' or MP with horizontal saccade was seen at or 1-2 cm rostral to the hand, arm or face area of the primary motor cortex (MI) in all four subjects investigated. This area exactly corresponded to the frontal eye field (FEF) identified by electrical stimulation. The amplitude of MRCPs with saccade was smaller than that with hand movements. On the mesial surface, within the supplementary motor area (SMA) proper, BP and/or NS' for horizontal saccade was located 1-2 cm rostral to that for hand and foot movements. BP and/or NS' delineated the supplementary eye field (SEF) at the rostral part of the SMA proper, and SEF partly overlapped with the hand and foot areas of the SMA proper. At the area just rostral to the vertical anterior commissure line and/or the pre-SMA defined by electrical stimulation, BP and/or NS' was seen invariably, regardless of the sites of movements, and in contrast with the SMA proper, there was no somatotopic representation. No clear MPs were elicited by eye movements on the mesial surface. In one of the two subjects whose MRCPs with horizontal saccade were recorded simultaneously from the lateral and mesial surfaces of the frontal lobe, BP from the SEF and pre-SMA preceded that from the FEF. It is concluded that MRCPs with horizontal saccade are useful for defining the FEF, SEF and pre-SMA, and that the SEF and pre-SMA become active in preparation for horizontal saccade earlier than the FEF.

Adolescent↗
PubMed2004

Role of lateral non-primary motor cortex in humans as revealed by epicortical recording of Bereitschaftspotentials.

In order to clarify the role of the lateral non-primary motor area in the control of voluntary movements, we studied movement-related cortical potentials (MRCPs) by direct epicortical recording from the lateral frontal lobe in nine patients with intractable partial epilepsy as a part of presurgical evaluation. We adopted movement tasks involving different body sites: eye closing, lip pursing, shoulder abduction, middle finger extension, thumb abduction, and foot dorsiflexion. We found that one or two small areas on the caudal lateral convexity of the frontal lobe generated pre-movement potential shifts regardless of the sites of movement (omni-Bereitschaftspotential; "omni-BP"). Such regions were located at or just rostral to the primary motor face area in six subjects, and at or rostral to the primary motor upper extremity area in three. Moreover, half of those areas were identified just adjacent (either rostral or caudal) to the primary negative motor area (PNMA), a cortical area of the lateral frontal lobe where negative motor responses were elicited by electric cortical stimulation. In conclusion, it is suggested that the lateral non-primary motor area plays a significant role, and has a close and direct relationship with other cortical areas in the frontal lobe, just like its counterpart on the mesial frontal cortex (supplementary negative motor area, SNMA).

Adolescent↗
PubMed2004

Propagation of tonic posturing in supplementary motor area (SMA) seizures.

We analyzed ictal motor symptoms in 10 patients diagnosed to have supplementary motor area (SMA) seizures based on ictal encephalographic (EEG) findings and ictal clinical semiology. Inclusion criteria were (1) EEG seizure pattern in the vertex for the scalp recording or in the area over and/or adjacent to SMA for epicortical recording and (2) ictal motor semiology characterized, as previously reported, by sudden and a brief tonic posturing of extremities and trunk mainly occurring during sleep without loss of consciousness. In 50% (5/10) of the patients, tonic posturing began in one part of the body and moved to other part(s) in 5-10s. Unlike Jacksonian march seen in seizures involving the primary sensorimotor area (S1-M1), it spread in no accordance with the somatotopy in S1-M1. The sequential propagation of tonic posturing may represent the somatotopic organization within the SMA proper.

Adolescent↗
PubMed2004

Rendu-Osler-Weber disease with a giant intracerebral varix secondary to a high-flow pial AVF: case report.

BACKGROUND: Intracranial varices are rare and most are associated with vein of Galen arteriovenous malformations (AVM) or fistulas (AVF). DESCRIPTION: A 43-year-old left-handed man presented with right hemihypesthesia and spastic gait. Neuroradiological examination revealed a spinal AVF and a giant intracerebral varix associated with a high-flow pial AVF. He had recurrent episodes of nasal bleeding, which were also confirmed in his mother's medical history, and telangiectases in the tip of his tongue and fingers. He was diagnosed with Rendu-Osler-Weber disease. After resection of the spinal AVF that produced his symptoms, we surgically exposed and obliterated the giant varix and AVF under intra- and postoperative hypotension and mild barbiturate therapy. The arteriovenous shunt was completely obliterated without hyperperfusion of the surrounding brain. CONCLUSION: This is an extremely rare case of Rendu-Osler-Weber disease with a giant intracerebral varix secondary to a high-flow pial AVF that did not involve the vein of Galen.

Adult↗
PubMed2004

The combination of mitotic and Ki-67 indices as a useful method for predicting short-term recurrence of meningiomas.

BACKGROUND: The most relevant factor in the progression-free survival (PFS) of patients with meningiomas is the malignant grade. However, using only the current World Health Organization (WHO) definition that does not consider precise quantitative indicators, an unequivocal diagnosis of the malignant grade is difficult. In our retrospective study of the PFS of meningioma patients, we focused on mitoses and the Ki-67 staining index of tumor specimens obtained at the initial surgery. METHODS AND RESULTS: A total of 349 patients with intracranial meningioma, operated between 1978 and 2000, were followed for a mean of 7 years. According to the mitotic index (MI), we classified them into 3 groups. In Group A (n = 326), slide-mounted tumor samples exhibited no mitoses; in Group B (n = 15) there were fewer than 4 mitoses, and in Group C (n = 8) 4 or more mitoses were seen per 10 high-power fields (HPF). The estimated 5-year PFS rates in Groups A, B, and C were 93%, 10%, and 13% respectively. The mean PFS for Group A was 148 months; in Groups B and C the median PFS was 43 and 16 months, respectively. A Ki-67 staining index (SI) of less than 1% corresponded with no mitosis, while an SI exceeding 5% was indicative of the presence of mitoses. CONCLUSION: In meningioma patients, no mitoses and/or a Ki-67 SI <1% signals a favorable outcome. An SI >5% or the presence of mitoses, even fewer than 4 in 10 HPF, is suggestive of a short PFS irrespective of other pathologic features. We suggest that in combination, assay of the Ki-67 SI and the MI represents a reliable, quantitative tool for predicting PFS in meningioma patients.

Adolescent↗