Biomedical subjects

Naoki Nakayama

Publications and source records attributed to Naoki Nakayama.

14 recordsLinked to original sources

PubMed2006

Involvement of CSF-1 in generating a stroma-independent hematopoietic stem cell line.

The hematopoietic stem cell line, Myl-D7, is maintained by a self-renewing stem cell population that spontaneously generates myeloid, lymphoid, and erythroid progeny. MS-5 stromal cells are necessary for the growth of Myl-D7 cells. One component of the Myl-D7 cells proliferation activity released by MS-5 stromal cells was enriched by Q sepharose fractionation and shown to be colony stimulating factor-1 (CSF-1) by Western blotting, BAC1.2F5 cell bioassay and inhibition of Myl-D7 proliferation by CSF-1 antibody. The requirement of Myl-D7 cells for CSF-1 was also demonstrated independently by selecting for rare, stroma-independent Myl-D7 mutant clones able to grow without stroma and additional factors. Eighty-nine stroma-independent mutant clones were obtained and belonged to two classes. The majority of mutants did not secrete any growth promoting activity. The second, rarer class of mutants releases a factor that stimulates proliferation/survival for up to several months and approximately half of the secretors express high levels of CSF-1 mRNA. Wild type Myl-D7 grown with supernatants from the secretor cells retained the stem cell phenotype. These data suggest that CSF-1 may act as a key factor in stroma-regulated hematopoiesis and cell-cell interaction.

Animals↗

PubMed2006

How does spontaneous hemostasis occur in ruptured cerebral aneurysms? Preliminary investigation on 247 clipping surgeries.

BACKGROUND: Rupture of cerebral aneurysms results in subarachnoid hemorrhage. In many cases, bleeding from aneurysms spontaneously arrests. Although bleeding from cerebral aneurysms has been reported to arrest from outside, bleeding from some aneurysms can arrest in different ways. METHODS: Between April 2002 and March 2004, we prospectively investigated mechanisms of spontaneous hemostasis in ruptured aneurysms by macroscopic examination when performing craniotomy and clipping surgeries. RESULTS: Hemostatic mechanisms were investigated in 247 patients with ruptured aneurysm (77 men, 170 women; age range, 25-95 years). Hemostatic mechanisms were divided into 3 different patterns. In the most common pattern (79.4%), the surface of the aneurysm rupture point was sealed from the outside by a platelet plug or fibrin net (outside-arrest pattern). In some aneurysms (10.1%), a thrombus or platelet plug was attached to the rupture point from inside the aneurysm (inside-arrest pattern). In a very small number of aneurysms (1.6%), a naked thrombus covered the hole made on the arterial wall or small remnant of the aneurysmal dome (bursting pattern) The mechanism remained unclear in the remaining 8.9% of aneurysms. Multivariate analysis revealed that alert consciousness on admission (WFNS grade I) significantly associated with usual hemostasis (outside arrest pattern: OR, 3.8; 95% CI, 1.4-10.0; P = .008). Borderline association with usual hemostasis was found in aneurysms with a size of 5 or smaller than 5 mm (OR, 2.6; 95% CI, 0.99-7.1; P = .052). CONCLUSIONS: The present preliminary study revealed that arrest of bleeding from a ruptured cerebral aneurysm does not always occur from outside the aneurysm. Unusual mechanisms of hemostasis are seen in approximately 12% of ruptured aneurysm. The outside-arrest-pattern aneurysm was more common for smaller aneurysms, and these patients tended to be of better grade. Further studies are necessary to explore the mechanism of hemostasis for ruptured cerebral aneurysms.

Adult↗

PubMed2006

Simultaneous superficial temporal artery to middle cerebral or anterior cerebral artery bypass with pan-synangiosis for Moyamoya disease covering both anterior and middle cerebral artery territories.

Some patients with moyamoya disease treated by conventional surgical procedures may develop postoperative refractory ischemia and perioperative cerebral infarction in the anterior cerebral artery (ACA) territory. We present a novel operative procedure for moyamoya disease to avoid the risk of ischemia in the ACA territory, which consists of simultaneous superficial temporal artery (STA) to middle cerebral artery (MCA) or ACA bypass with pan-synangiosis, encephalo-duro-arterio-myo-synangiosis for the lateral frontal and temporal areas, and encephalo-galeo-arterio-synangiosis for the medial frontal area. This procedure can establish direct bypass to the ACA territory at the first intervention. Simultaneous STA-MCA and STA-ACA bypasses with pan-synangiosis is suitable for patients with moyamoya disease associated with severely impaired perfusion of the ACA territory requiring direct bypass surgery.

Adolescent↗

PubMed2005

Novel magnetic resonance angiography stage grading for moyamoya disease.

BACKGROUND: Magnetic resonance angiography (MRA) has been acknowledged as a noninvasive diagnostic modality for moyamoya disease. However, in terms of staging of moyamoya disease, conventional angiography is still the gold standard. Therefore, the purpose of this study was to establish MRA grades for moyamoya disease as an alternative to conventional angiography. METHODS: Twenty-two patients (44 sides) with moyamoya disease diagnosed by conventional angiography were evaluated by MRA during the past 5 years. MRA scores were assigned based on the severity of occlusive changes of the internal carotid artery, the horizontal portion of the middle cerebral artery, the anterior and the posterior cerebral arteries and the signals of the distal branches of these arteries. Total points ranged from 0 (normal) to 10 (most severe). RESULTS: MRA scores (0-10) were significantly consistent with the conventional angiographic staging. Four grades based on this novel MRA scores correlated well with Suzuki's stages, with high sensitivity and specificity. CONCLUSIONS: These novel MRA grades can be a reliable alternative to conventional staging. By employing these novel MRA grades, the use of conventional angiography can be avoided for the purpose of evaluation of the stages of moyamoya disease.

Adolescent↗

PubMed2005

Isotropic component trace analysis.

A new method for analyzing diffusion tensor imaging (DTI) of the brain, based on a recently introduced algorithm, lambda chart analysis (LCA), is presented. Pre-treatment of a given DTI data set with LCA, which effectively segregates isotropic and anisotropic components, allows for total removal of the anisotropic component from the DTI data set. The remaining pure isotropic component can therefore be subjected to further analysis similar to that applied in the trace histogram method. Deconvolution of the trace function yielded 3 Gaussian elements. Remapping of these 3 deconvoluted isotropic elements back onto the 2-dimensional image plane provided anatomical correlates of each element. The algorithm, referred to here as isotropic component trace analysis, can be used as a pictorial analytic tool, as well as a numerical analytical tool, for the noninvasive assessment of isotropic parenchymal components. The presented method provides quantitative indices of certain parenchymal parameters with better clarity than currently available methods. A ready-to-use program, EZ-LCA, for this powerful method is provided (available at http://coe.bri.niigata-u.ac.jp).

Algorithms↗

PubMed2005

Prevalence of asymptomatic microbleeds in patients with moyamoya disease.

Basal moyamoya vessels are a potential source of hemorrhage in patients with moyamoya disease, but the etiology remains unclear. Symptomatic hemorrhage resulting from long-standing hemodynamic effects on pathologically dilated, fragile moyamoya vessels may be preceded by asymptomatic microbleeding in adult moyamoya disease patients, regardless of hemorrhagic or ischemic onset. T2*-weighted magnetic resonance (MR) imaging was used to investigate the presence of microbleeds in 27 adult patients with angiographically confirmed moyamoya disease, 21 females and six males aged 18-70 years (mean 40.8 +/- 15.7 years). Clinical diagnosis was intracranial bleeding in six patients, transient ischemic attack or cerebral infarction in 18, and asymptomatic in three. Asymptomatic microbleeds were detected in four of the 27 patients, two of six who initially presented with hemorrhagic events and two of 18 with ischemic onset. These microbleeds were located in the paraventricular white matter, temporal subcortex, and basal ganglia. The presence of microbleeds had no correlation with either patient age or duration from disease onset or diagnosis of disease. A large cohort study is needed to explore the significance of asymptomatic microbleeds in moyamoya disease.

Adolescent↗

PubMed2005

[Vascular reconstructive surgery for elderly patients with internal carotid artery stenosis at the cervical portion].

PURPOSE: We encounted increasing numbers of elderly patients suffering from stenotic lesions of the cervical internal carotid artery. Most of them have been considered to indicate a need for carotid artery stenting. The purpose of this study was to clarify with regard to the modality of treatment and perioperative complications the effectiveness of vascular reconstruction procedure in elderly patients. PATIENTS AND METHODS: Ninety eight lesions in 91 patients with stenosis of the internal carotid artery were treated surgically. Eighty lesions received carotid endarterectomy (CEA), and 18 lesions received percutaneous transluminal angioplasty (PTA) with or without stent. Treatment with PTA-with-or-without-stent has been opted in cases of patient with such conditions as radiation-induced stenosis, re-stenosis after CEA, unfitness for general anesthesia, bilateral lesions both of which need to be reconstructed with in a short interval. We divided the patients into 4 groups according to their age; under 70-year-old group, 70-to-74-year old group, 75-to-79-year old group, and over 80-year-old group. Vasoreconstructive procedures were performed for 41 patients in the under 70-year-old group, for 31 in the 70-to-74-year old group, for 21 in the 75-to-79-year old group, and for 5 in the over 80-year-old group. RESULT: The overall surgical morbidity rate was 2% (2 of 98 cases) and there was no mortality. Tweleve patients (12.2%) experienced transient neurological deficits. Two patients exhibited perioperative complications in gastrointestinal organs, but none of the patients experienced cardiac complications. Elderly patients tend to experience systemic complications such as gastrointestinal complications as well as transient neurological deficits, which appear as restlessness, possibly due to hyperperfusion syndrome. The perioperative complication rate in elderly patients (putting the patients of the 70-to-74-year old group, the 75-to-79-year old group, and the over 80-year-old group together) was, statistically, significantly higher than those in patients of under the 70-year-old group. However, when two treatment modalities, CEA and PTA-with-or-without stent, were compared, there was no significant difference in the perioperative complication rate. CONCLUSION: Careful patient selection and prudent perioperative management enabled us to perform vasoreconstructive surgery even for elderly patients with internal carotid artery stenosis in a relatively safe manner with an acceptable complication rate. Decision making in selecting treatment modality, CEA or PTA with or without stent, should not be based solely on aging.

Age Factors↗

PubMed2004

Determinants of intellectual outcome after surgical revascularization in pediatric moyamoya disease: a multivariate analysis.

OBJECTS: The aim of this study was to clarify predictors for poor intellectual outcome in pediatric moyamoya disease. METHODS: Fifty-two pediatric patients were included. Clinical diagnosis was transient ischemic attacks (TIA) in 35 and completed stroke in 17. Ten patients underwent indirect synangiosis through "small craniotomy," whereas the other 42 underwent superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis and indirect synangiosis through "large craniotomy." Full-scale IQ (FSIQ) was measured using the Wechsler intelligence scale for children (WISC) after surgery. Multivariate logistic regression models were applied to test the effect of clinical factors on intellectual outcome. RESULTS AND CONCLUSION: Eight patients revealed mentally impaired status (FSIQ<70). Multivariate analysis revealed that completed stroke and "small craniotomy" surgery were significantly associated with poor intellectual outcome. Odds ratios of each factor were 33.4 (95% CI, 2.4-474) and 19.6 (95% CI, 1.8-215) respectively. Early diagnosis and the revascularization procedure over as wide an area as possible may be essential to improve their intellectual outcome.

Cerebral Revascularization↗

PubMed2004

How does angiogenesis develop in pediatric moyamoya disease after surgery? A prospective study with MR angiography.

OBJECT: The dynamic process of neovascularization seen in patients with moyamoya disease who have received bypass surgery has not been sufficiently elucidated. Magnetic resonance angiography (MRA)is expected to disclose this process since it can be conducted frequently because of its non-invasive nature. In this study, we prospectively investigated postoperative neovascularization using repeated MRA. METHODS: We studied 14 pediatric patients (23 sides) who have received both direct bypass surgery of the superficial temporal artery (STA) to middle cerebral artery and indirect surgery of encephalo-duro-arterio-myo-synangiosis during the past 3 years. MRA was performed using a 1.5-T machine, image sequences of 512 x 256 resolution, and the time-of-flight method. MRA was prospectively performed preoperatively and repeated 1, 3, and 6 months after surgery. CONCLUSIONS: A tendency toward a decrease in moyamoya vessels and the development of the STA was observed 1 month after the surgery. Development of the deep temporal artery and the middle meningeal artery was observed 3 months after the surgery. The progression of stenotic change was apparently accelerated after the surgery. A reciprocal relation between neovascularization artificially induced by bypass surgery and moyamoya vessels, which are supposed to compensate for the stenotic change of the internal carotid artery, was disclosed.

Cerebral Revascularization↗

PubMed2003

A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in chondrocytes of developing cartilage and osteoarthritic joint cartilage.

We have identified a novel chordin-like protein, CHL2, which is structurally most homologous to CHL/neuralin/ventroptin. When injected into Xenopus embryos, CHL2 RNA induced a secondary axis. Recombinant CHL2 protein interacted directly with BMPs in a competitive manner to prevent binding to the type I BMP receptor ectodomain, and inhibited BMP-dependent induction of alkaline phosphatase in C2C12 cells. Thus, CHL2 behaves as a secreted BMP-binding inhibitor. In situ hybridization revealed that CHL2 expression is restricted to chondrocytes of various developing joint cartilage surfaces and connective tissues in reproductive organs. Adult mesenchymal progenitor cells expressed CHL2, and its levels decreased during chondrogenic differentiation. Addition of CHL2 protein to a chondrogenic culture system reduced cartilage matrix deposition. Consistently, CHL2 transcripts were weakly detected in normal adult joint cartilage. However, CHL2 expression was upregulated in middle zone chondrocytes in osteoarthritic joint cartilage (where hypertrophic markers are induced). CHL2 depressed chondrocyte mineralization when added during the hypertrophic differentiation of cultured hyaline cartilage particles. Thus, CHL2 may play negative roles in the (re)generation and maturation of articular chondrocytes in the hyaline cartilage of both developing and degenerated joints.

Alkaline Phosphatase↗

PubMed2003

Macroscopic cartilage formation with embryonic stem-cell-derived mesodermal progenitor cells.

The totipotent embryonic stem cell generates various mesodermal cells when stimulated with BMP4. Among the resulting cells, those expressing flk-1 and/or PDGFRalpha displayed chondrogenic activity in the presence of TGFbeta3 and expressed cartilage-specific genes in 7 to 16 day pellet cultures. Depositions of cartilage matrix and type II collagen were detected by day 14. TGFbeta-stimulated chondrogenesis was synergistically enhanced by PDGF-BB, resulting in a larger cartilage particle filled with a cartilaginous area containing type II collagen, with a surface cell layer expressing type I collagen. In contrast, noggin inhibited both the TGFbeta- and TGFbeta+PDGF-stimulated cartilage formation, suggesting that a BMP-dependent pathway is involved. In fact, replacement of TGFbeta3 with BMP4 on days 10 to 12 markedly elevated the cartilage matrix deposition during the following 7 to 8 days. Moreover, culture with TGFbeta3 and PDGF-BB, followed by the incubation with BMP4 alone, resulted in a cartilage particle lacking type I collagen in the matrix and the surface layer, which suggests hyaline cartilage formation. Furthermore, such hyaline cartilage particles were mineralized. These studies indicate that the PDGFRalpha+ and/or flk-1+ cells derived from embryonic stem cells possess the full developmental potential toward chondrocytes, in common with embryonic mesenchymal cells.

Animals↗

PubMed2003

All-phase MR angiography using independent component analysis of dynamic contrast enhanced MRI time series: phi-MRA.

Dynamic contrast enhanced magnetic resonance imaging (dynamic MRI) represents a MRI version of non-diffusible tracer methods, the main clinical use of which is the physiological construction of what is conventionally referred to as perfusion images. The raw data utilized for constructing MRI perfusion images are time series of pixel signal alterations associated with the passage of a gadolinium containing contrast agent. Such time series are highly compatible with independent component analysis (ICA), a novel statistical signal processing technique capable of effectively separating a single mixture of multiple signals into their original independent source signals (blind separation). Accordingly, we applied ICA to dynamic MRI time series. The technique was found to be powerful, allowing for hitherto unobtainable assessment of regional cerebral hemodynamics in vivo.

Aged↗

PubMed2003

[Clinical features and outcomes of 10 asymptomatic adult patients with moyamoya disease].

Recent development of non-invasive diagnostic technology, such as magnetic resonance imaging (MRI) and angiography (MRA), is believed to have made possible on increase in the diagnoses of asymptomatic moyamoya disease. However, no criteria have been established for the management of such cases. The present study aimed to clarify the natural history of asymptomatic moyamoya disease retrospectively. Ten patients were included in this study. None of them had experienced any episode due to moyamoya disease and were only incidentally diagnosed as having moyamoya disease. There were 4 males and 6 females. Their ages ranged from 30 to 67 years, with the mean age of 46.2. Cerebral angiography showed there was the tendency of disease progression in elder patients. MRI detected cerebral infarction in 3 of 10 patients (30%). Hemodynamic ischemia, such as impaired reactivity to acetazolamide and/or elevated oxygen extraction fraction, was observed in 4 of 10 patients. Only one patient underwent surgical revascularization. Antiplatelet or anticonvulsant medication was administered in 5 of 10 patients. The mean follow-up period was 4.1 years, ranging from 0.5 to 13 years. During follow-up periods, the moyamoya lesion markedly progressed and caused cerebral infarction in one patient. However, neither ischemic nor hemorrhagic stroke occurred in the other 9 patients. Multi-center nation-wide study should be planned to clarify the natural course of asymptomatic moyamoya disease and establish the management guidelines for patients with asymptomatic moyamoya disease.

Adult↗

PubMed2002

Embryonal subregion-derived stromal cell lines from novel temperature-sensitive SV40 T antigen transgenic mice support hematopoiesis.

Throughout life, the hematopoietic system requires a supportive microenvironment that allows for the maintenance and differentiation of hematopoietic stem cells (HSC). To understand the cellular interactions and molecules that provide these functions, investigators have previously established stromal cell lines from the late gestational stage and adult murine hematopoietic microenvironments. However, the stromal cell microenvironment that supports the emergence, expansion and maintenance of HSCs during mid-gestational stages has been largely unexplored. Since several tissues within the mouse embryo are known to harbor HSCs (i.e. aortagonads-mesonephros, yolk sac, liver), we generated numerous stromal cell clones from these mid-gestational sites. Owing to the limited cell numbers, isolations were performed with tissues from transgenic embryos containing the ts SV40 Tag gene (tsA58) under the transcriptional control of constitutive and ubiquitously expressing promoters. We report here that the growth and cloning efficiency of embryonic cells (with the exception of the aorta) is increased in the presence of the tsA58 transgene. Furthermore, our results show that the large panel of stromal clones isolated from the different embryonal subregions exhibit heterogeneity in their ability to promote murine and human hematopoietic differentiation. Despite our findings of heterogeneity in hematopoietic growth factor gene expression profiles, high-level expression of some factors may influence hematopoietic differentiation. Interestingly, a few of these stromal clones express a recently described chordin-like protein, which is an inhibitor of bone morphogenic proteins and is preferentially expressed in cells of the mesenchymal lineage.

Animals↗