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Biomedical subjects

Shunro Endo

Publications and source records attributed to Shunro Endo.

At least 55 records · Page 3Linked to original sources

Mechanism of activation of heparin cofactor II by calcium spirulan.

Calcium spirulan (Ca-SP), a novel sulfated polysaccharide, increases the rate of thrombin inhibition by heparin cofactor II (HCII) more than 1000-fold through a mechanism not requiring the amino-terminal acidic domain of HCII. Activation of HCII by Ca-SP was molecular-weight dependent. Furthermore, HD22, an aptamer that binds exosite II of thrombin, produced a concentration-dependent, 15-fold reduction at 5 microM in the rate of thrombin inhibition by HCII with Ca-SP, suggesting that Ca-SP interacts with exosite II of thrombin. Mutations of Lys173 to Leu (K173L) and Arg189 to Leu (R189L) in the HCII molecule resulted in large decreases in the rate of thrombin inhibition mediated by Ca-SP and in the NaCl concentration needed for elution from Ca-SP-Toyopearl. Mutations of Lys173 to Arg (K173R) and Arg189 to Lys (R189K) showed inhibition of thrombin similar to wild-type rHCII (wt-rHCII). These results indicate that Ca-SP binds to the positive charges of Lys173 and Arg189 on the HCII molecule. In the thrombin inhibitory process by HCII, Ca-SP appears to play as a template by binding to both thrombin and HCII.

Amino Acid Substitution↗

Development-associated myristoylated alanine-rich C kinase substrate phosphorylation in rat brain.

OBJECT: In neuronal cells, myristoylated alanine-rich C kinase substrate (MARCKS), localized to particular areas of the synaptic membrane, is active during brain development. The destination of phosphorylated MARCKS is thought to be the cytoplasm where it is probably inactive. We compared MARCKS phosphorylation in the brains of embryonic, perinatal, and adult rats to determine its possible involvement in neurogenesis. METHODS: We prepared crude and partially purified extracts from various brain regions of rats aged between embryonic day 14 (E14) and 7 weeks after birth and assayed them for MARCKS phosphorylation by immunochemical methods. The isotypes of protein kinase C (PKC) were immunochemically identified in crude brain extracts from embryonic and postnatal rats. Despite negligible MARCKS phosphorylation, E16 brain extracts contained both MARCKS and PKCgamma, delta, epsilon, and lambda. MARCKS and polypeptides were clearly phosphorylated (49 and 45 kDa, respectively) in brain extracts purified on a DE52 column. Embryonic brain extracts manifested a high-molecular-weight activity capable of suppressing polypeptide phosphorylation. This activity was markedly decreased on the day of birth and almost undetectable in the brains of 9-day-old rats. CONCLUSIONS: The embryonic rat brain appears to contain a protein(s) that suppresses the phosphorylation of other proteins including MARCKS. We posit that this inhibitory activity represents a factor(s) that plays a role in the regulation of neurogenesis beginning on the day on which MARCKS appears in the embryonic brain.

Animals↗

Representation of place by monkey hippocampal neurons in real and virtual translocation.

The hippocampal formation (HF) is hypothesized as a neuronal substrate of a cognitive map, which represents environmental spatial information by an ensemble of neural activity. However, the relationships between the hippocampal place cells and the cognitive map have not been clarified in monkeys. The present study was designed to investigate how activity patterns of place-selective neurons encode spatial relationships of various environmental stimuli; to do this, we used multidimensional scaling (MDS) for hippocampal neuronal activity in the monkey during the performance of real and virtual translocation. Of 389 neurons recorded from the monkey HF and parahippocampal gyrus (PH), 166 had place fields that displayed increased activity in a specific area of an experimental field and/or on a monitor (place-selective neurons). The MDS transformed relationships among the 16 places in the experimental field and the monitor, expressed as correlation coefficients between all possible pairs of two places based on the 166 place-selective responses, into geometric relationships in a two-dimensional MDS space. In the real translocation tasks, the 16 places were distributed throughout the MDS space, and their relative positions were well correlated to real positions in the experimental laboratory. However, the correlation between the MDS space and real arrangements was significantly smaller in virtual than real translocation tasks. The present results strongly suggest that activity patterns of the HF and PH neurons represent spatial information and might provide a neurophysiological basis for a cognitive map.

Animals↗

A method for accurate determination of stereotaxic coordinates in single-unit recording studies in monkeys by high-resolution three-dimensional magnetic resonance imaging.

For single-unit recording from the brain in monkeys, the precise determination of recording targets is essential. Although magnetic resonance imaging (MRI) has been used recently in several laboratories, it has been difficult to obtain three-dimensional information on a target from two-dimensional pictures, and, therefore, it has also been difficult to determine precise coordinates. We developed a new method for precisely determining target-area coordinates based on reconstructed rendering pictures made from three-dimensional MRI data. We also combined this method with magnetic resonance angiography to avoid severe vessel complications in recording experiments.

Animals↗

A rare case of dysembryoplastic neuroepithelial tumour in occipital lobe presenting with only headache.

We report an unusual case of dysembryoplastic neuroepithelial tumour (DNT) located in the occipital lobe presenting with only headache. A 31 year old woman presented with headache. She had no history of epilepsy and neurological examination revealed no abnormal findings. Computed tomography (CT) scanning revealed a multilobulated mass lesion with calcification in the right occipital lobe. Magnetic resonance (MR) imaging demonstrated a heterogeneously enhanced mass with hypointense signals on T1- and hyperintense signals on T2-weighted images. The lesion was totally resected and histopathologically diagnosed as DNT. Physicians must bear in mind that DNT may occur in the occipital lobe and present with only mass effect.

Adult↗

Multiple meningiomas consisting of fibrous meningioma and anaplastic meningioma.

A 61-year-old woman presented with progressive dementia over a period of 4 months. Computed tomographic (CT) scans and magnetic resonance (MR) imaging showed 2 meningiomas located at the left parasagittal region and the left sphenoid ridge. These tumors had distinct MRI findings; the left parasagittal tumour showed a clear peritumoral CSF space without brain oedema, but the sphenoid ridge tumour was large with marked peritumoral oedema. Total excision of these 2 tumours was attempted with favourable clinical improvement and histological studies revealed meningiomas of different histological types. The left parasagittal tumour was a fibrous meningioma and the left sphenoid ridge tumour was an anaplastic meningioma with typical brain invasion. These tumours showed a MIB-1 staining index of 1% and 30%, respectively. There was also a difference in the immunohistochemical findings for neurofibromin (NF1 product) expression; the left parasagittal tumour expressed neurofibromin but the left sphenoid ridge tumour lacked neurofibromin expression, suggesting an NF1-gene mutation. This case may be a rare example of the simultaneous occurrence of meningiomas with distinct genotypes.

Female↗

In vitro and in vivo growth inhibition of human malignant astrocytoma cells by the farnesyltransferase inhibitor B1620.

p21-Ras, the protein product of the proto-oncogene Ras is overactivated in malignant astrocytomas despite the absence of mutation. It is known that p21-Ras participates in signaling events from membrane tyrosine kinase receptors and a variety of intracellular biochemical pathways to downstream targets. Signal transduction inhibition by targeting against Ras is now thought to be a promising therapeutic strategy for malignant astrocytomas. This study demonstrates that Ras pathway inactivation by a farnesyltransferase inhibitor, B1620, effectively inhibits in vitro and in vivo growth of human astrocytoma cells, although normal human astrocytes (NHA) derived from fetal brain are resistant to B1620. Anti-proliferative effect of B1620 on in vitro growth of astrocytoma cells was examined by MTT assays and soft agar colony formation assay. B1620 inhibited anchorage-dependent growth of six astrocytoma cell lines with a median effective dose (IC50) ranging from 2.0 to 20.7 microM. However, growth of NHA was not significantly affected by B1620 even at the concentration of 100 microM. All astrocytoma cells showed apoptotic figures after Hoechst 33258 staining, when treated for 5 days at each IC50 concentration against B1620. Anchorage-independent growth of these astrocytoma cell lines was inhibited at a much lower concentration than that of anchorage-dependent growth. Daily treatment of U87 xenograft-bearing athymic mice with B1620 at 100 or 50 mg kg(-1) resulted in significant inhibition of tumor growth. A histological study of the B1620-treated tumor tissue showed decreased vascularity with numerous TUNEL-positive apoptotic cells. These results suggest that the mechanism of the growth-inhibitory effect of B1620 is anti-angiogenesis, apoptosis induction and reversion of the transformed phenotype. The potential clinical use of B1620 could be expanded to malignant astrocytomas.

Alkyl and Aryl Transferases↗

Independent predictors of late hydrocephalus in patients with aneurysmal subarachnoid hemorrhage--analysis by multivariate logistic regression model.

OBJECT: We determined independent variables contributing to the development of late hydrocephalus after subarachnoid hemorrhage (SAH). METHODS: A total of 114 consecutive patients who underwent surgery for aneurysms within 72 h after SAH were studied. Thirty-nine patients underwent ventriculoperitoneal shunt (VPS) placement (14 patients within 30 days and 25 patients more than 30 days after onset). Univariate and multivariate analyses were performed to assess relationships among various variables and shunt placement. RESULTS: Three variables were found to be independently associated with VPS patients: (1) the rate of SAH clearance; (2) the duration of external cerebrospinal fluid drainage, and (3) presence of neurological deficits 2 weeks after surgery, which indicates brain damage mainly caused by intraoperative manipulation and cerebral vasospasm. CONCLUSION: As in previous reports, intraoperative clot removal and duration of external CSF drainage were found to be closely related to the incidence of hydrocephalus. Brain damage due to intraoperative manipulation and cerebral vasospasm is seemed to be involved in the occurrence of late hydrocephalus in this study.

Adult↗

Neuroendoscopic septostomy for isolated lateral ventricle.

The clinical features and endoscopic findings were investigated in 20 patients with isolated lateral ventricle treated by neuroendoscopic septostomy to establish cerebrospinal fluid communication and open an isolated ventricular compartment. The endoscopic procedure was incomplete because of thickened septum pellucidum and insufficient working space in two adults with postmeningitic hydrocephalus. Two children underwent second septostomy. In all other cases, results were good and there were no complications related to endoscopic procedures. Endoscopic septostomy is less invasive and has few complications. Intraoperative navigation and the biportal approach may be required in difficult cases with multiple septum formation and severe postmeningitic hydrocephalus. Adequate stomal size is required in high-risk groups including children under 2 years of age.

Aged↗

Independent predictors of recurrence of chronic subdural hematoma: results of multivariate analysis performed using a logistic regression model.

OBJECT: The authors attempted to determine independent predictors that contribute to the recurrence of chronic subdural hematoma (CSDH). METHODS: A total of 105 consecutive patients who underwent surgery for CSDH were included in this study. Eleven patients underwent a repeated operation because the CSDH recurred. Univariate and multivariate analyses were performed to assess the relationships among various variables and CSDH recurrence. Finally, four variables were found to be independently associated with the recurrence of CSDH: 1) absence of a multiplicity of hematoma cavities on CT scans; 2) presence of a history of seizure; 3) width of the hematoma; and 4) absence of a history of diabetes mellitus (DM). CONCLUSIONS: As previously reported, the width of the hematoma is related to the incidence of CSDH recurrence. In this study, the lack of a multiplicity of hematoma cavities was the favorite predictor of CSDH recurrence. In addition, histories of seizure and no past DM are closely related to the incidence of CSDH recurrence.

Adult↗

[A case of the traumatic hydrocephalus after large craniectomy for acute subdural hematoma].

Decompressive craniectomy sometimes causes neurological deficits known as 'the syndrome of the sinking skin flap' or 'the symptom of the trephined'. These disorders can be corrected with cranioplasty, but there is no consensus on appropriate treatments. We report a case of successful correction of traumatic hydrocephalus following craniotomy. A 50-year-old man was admitted to our hospital with disturbance of consciousness after a head injury. Decompressive craniectomy was performed for a right acute subdural hematoma. His consciousness recovered after the operation, but then deteriorated gradually and left hemiparesis occurred. CT scan revealed midline shift from right to left. These symptoms and CT findings were not improved after cranioplasty, but were improved with removal of the CSF from the adhered subarachnoid space. The diagnosis was traumatic hydrocephalus, and a cisternoperitoneal shunt was subsequently placed. We report this case to emphasize the necessity for study of CSF circulation, as well as the importance of examination of CBF and ICP after craniectomy.

Craniotomy↗

[A case of basilar artery occlusion of traumatic vertebral artery dissection successfully managed by endovascular treatment].

The author describes a case of basilar artery occlusion caused by vertebral artery dissection with vertebral fracture. A 61-year-old man was admitted with neck pain after a traffic accident. His symptoms suddenly deteriorated and cerebral angiography revealed an occlusion of the right vertebral artery, and complete occlusion of the basilar artery. Local-arterial fibrinolysis with urokinase for basilar artery occlusion and angioplasty with the use of a self-expandable stent for the site of the vertebral artery dissection was performed, and the basilar artery was partially recanalized. The patient's symptoms gradually improved. It should be emphasized that in cases of acute cervical spine injury after major trauma, vertebral artery dissection should be considered. Local-arterial fibrinolysis and angioplasty using a self-expandable stent was regarded as a useful treatment for basilar artery occlusion caused by vertebral artery dissection, in the acute stage.

Arterial Occlusive Diseases↗

[A survival case of fluminant meningitis and multiple organ failure as overwhelming postsplenectomy infection (OPSI) syndrome].

A 39-year-old man, who had splenectomy following abdominal trauma 30 years previously, admitted to our hospital with high fever, headache and convulsion on January 8, 2002. Examination of cerebrospinal fluid (CSF) showed pleocytosis up to 10,000 cells/mm3 with polymorphonuclear cells dominant and elevated protein to 330 mg/dl and reduction of glucose to 15 mg/dl. Streptococcus pneumoniae was detected at the culture of CSF and blood. We diagnosed him as having pneumococcal meningitis as overwhelming postsplenectomy infection(OPSI) syndrome. After administration of carbapenem antibiotics, methylprednisolone (1,000 mg) and immunoglobulin, he survived without any complications. Splenectomized patients are likely to suffer from severe infections, such as sepsis and meningitis, which is called OPSI syndrome. The course is rapid, the clinical symptoms are serious, and the prognosis is very poor. It is important for splenectomized patients to receive the vaccine, antibiotic prophylaxis and seek medical attention at the earliest sign of minor infection.

Adult↗

[Three-dimensional DSA imaging and 3-dimensional measurement of cross section for internal carotid artery stenosis].

We have performed rotational DSA for internal carotid artetry (ICA) stenosis and examined cross sectional imaging of the stenosis. Then, we compared the area stenosis rate (ASR) with stenosis rate by NASCET method and with results of duplex carotid ultrasonography. Of consecutive 451 patients who underwent digital subtraction angiography, 28 patients with ICA stenosis were selected for this study. Imaging data were transmitted to a workstation, and three-dimension (3-D) images were prepared, and cross sectional images of the highest-grade stenotic portion were obtained. ASRs were calculated [1-(the area of highest stenotic portion of ICA/the area of distal ICA)] x 100, which were compared with stenosis rates by NASCET method, as well as peak systolic velocity ratios (PSVR) of ICA to common carotid artery (CCA) determined by duplex carotid ultrasonography (USG). Cross sectional images in all patients were made except for restless patients, thereby morphology of the stenosis was feasible and measurements of cross section and diameter were possible. ASR and stenosis rate by NASCET method showed a very high correlation, and ASR was obtained by formula of (12.886 + 1.037 x stenosis rate by NASCET method). In patients with distorted stenosis, the stenosis rate was overestimated by NASECT method. ICA/CCA PSVR could predict stenosis to some extent, and in particular, all the patients with ICA/CCA PSVR of 3.1 or greater were found to have high grade stenosis. However duplex carotid USG failed to detect stenosis in a patient with high-grade stenosis at high position. In conclusion, as to ICA stenosis, 3-D image could show the stenosis precisely, and was considered to be useful as a routine examination.

Aged↗

Hydroxyapatite ceramics as a particulate embolic material: report of the physical properties of the hydroxyapatite particles and the animal study.

BACKGROUND AND PURPOSE: Hydroxyapatite ceramic microparticles are newly developed embolic materials. The purpose of this study was to evaluate the characteristics, embolic properties of hydroxyapatite ceramic microparticles, and effects of transcatheter embolization from an angiographic standpoint and to histopathologically evaluate the results of animal experimentation. METHODS: After physical evaluation of the characteristics and embolic properties of hydroxyapatite microparticles (100-250 micro m in diameter), microcatheter superselective renal artery embolization was performed in rabbits by using this material. Follow-up angiography and histopathologic study of 18 rabbits were performed at different intervals within 24 weeks after embolization. RESULTS: No microcatheter clogging was observed because of excellent visibility of this material in the suspension and because of its excellent navigability due to its nearly oval shape with no "spines." Angiographic renal arterial devascularization was consistently obtained without unexpected proximal occlusions; follow-up angiography showed persistent occlusion. Histopathologic evaluation confirmed satisfactory embolization of peripheral arteries. Chronic inflammatory cells were observed in several vessels containing hydroxyapatite microparticles. No evidence of angionecrosis, hemorrhage, or extraluminal migration was noted in any sections. CONCLUSION: Hydroxyapatite microparticles are excellent biocompatible embolic materials with good visibility during injection control, capable of producing effective occlusion of the distal arteriocapillary bed.

Animals↗

Hydroxyapatite ceramics as a particulate embolic material: report of the clinical experience.

BACKGROUND AND PURPOSE: Our newly developed biocompatible embolic materials, hydroxyapatite ceramic microparticles, have good visibility during injection control and were shown to be capable of producing effective occlusion of the distal arteriocapillary bed in an experimental animal study. The purpose of this present study was to evaluate hydroxyapatite ceramic microparticles for use in human meningioma embolization. METHODS: Thirteen patients with meningiomas underwent preoperative superselective embolization with the use of hydroxyapatite microparticles. Radiologic and histopathologic studies of the surgical specimens were performed. RESULTS: During embolization, no microcatheter clogging was observed and angiographic devascularization was consistently obtained without unexpected proximal occlusions. Histopathologic findings showed that there was mild inflammatory response in the thrombosed lumen. CONCLUSION: Hydroxyapatite microparticles are excellent embolic materials for the treatment of human meningioma. They have excellent biocompatibility and good injection control, which produces occlusion of the distal arteriocapillary bed.

Adult↗

Lipophilic fraction of Panax ginseng induces neuronal differentiation of PC12 cells and promotes neuronal survival of rat cortical neurons by protein kinase C dependent manner.

Panax ginseng is a traditional Chinese herb with a wide range of therapeutic benefits. Recent studies focusing on its effect on the central nervous system have revealed that ginseng has neurotrophic effects including differentiation of neurons. However, most studies involve use of the water-soluble fraction called saponin, and little is known about the effect of the lipophilic fraction. In the present study, we have shown that the lipophilic fraction of ginseng at a concentration of between 0.1 and 50 microg/ml can induce neurite outgrowth of PC12 cells in a dose-dependent manner. Nearly all cells showed morphological differentiation in response to the lipophilic fraction. This morphological differentiation of PC12 cells appeared to be similar to that of NGF. The lipophilic fraction of ginseng also induced neurite extension and promoted survival of rat cortical neurons at a concentration of between 0.025 and 1 microg/ml. These neurotrophic effects on PC12 cells and cortical neurons were not inhibited by K252b, which selectively blocks neurotrophin actions by inhibiting trk-type receptor tyrosine phosphorylation. This suggests that trks do not participate in the neurotrophic action of the lipophilic fraction. However, the effects were completely attenuated by sphingosine, polymyxin B or staurosporin, known inhibitors of protein kinase C (PKC) and calmodulin-dependent kinases. Our results suggest that the lipophilic fraction of ginseng exerts its neurotrophic effects via PKC-dependent pathways.

Animals↗

Contribution of basic residues of the A helix of heparin cofactor II to heparin- or dermatan sulfate-mediated thrombin inhibition.

Inhibition of thrombin by heparin cofactor II (HCII) is accelerated 1000-fold by heparin or dermatan sulfate. To investigate the contribution of basic residues of the A helix of HCII to this activation, we constructed amino acid substitutions (K101Q, R103L, and R106L) by site-directed mutagenesis. K101Q greatly reduced heparin cofactor activity and required a more than 10-fold higher concentration of dermatan sulfate to accelerate thrombin inhibition compared with wild-type recombinant HCII. Thrombin inhibition by R106L was not significantly stimulated by dermatan sulfate. These results provide evidence that basic residues of the A helix of HCII (Lys(101) and Arg(106)) are necessary for heparin- or dermatan sulfate-accelerated thrombin inhibition.

Amino Acid Sequence↗