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T Yamashima

Publications and source records attributed to T Yamashima.

At least 19 recordsLinked to original sources
PubMed2006

Expression of angiogenic and neurotrophic factors in the progenitor cell niche of adult monkey subventricular zone.

The subventricular zone along the anterior horn (SVZa) of the cerebral lateral ventricle of adult mammals contains multipotent progenitor cells, which supposedly exist in an angiogenic niche. Numerous signals are known to modulate the precursor cell proliferation, migration or differentiation, in rodent models. In contrast, the data on signals regulating the primate SVZa precursors in vivo are scarce. We analyzed the expression at protein level of a panel of angiogenic and/or neurotrophic factors and their receptors in SVZa of adult macaque monkeys, under normal condition or after transient global ischemia which enhances endogenous progenitor cell proliferation. We found that fms-like tyrosine kinase 1 (Flt1), a receptor for vascular endothelial cell growth factor, was expressed by over 30% of the proliferating progenitors, and the number of Flt1-positive precursors was significantly increased by the ischemic insult. Smaller fractions of mitotic progenitors were positive for the neurotrophin receptor tropomyosin-related kinase (Trk) B or the hematopoietic receptor Kit, while immature neurons expressed Flt1 and the neurotrophin receptor TrkA. Further, SVZa astroglia, ependymal cells and blood vessels were positive for distinctive sets of ligands/receptors, which we characterized. The presented data provide a molecular phenotypic analysis of cell types comprising adult monkey SVZa, and suggest that a complex network of angiogenic/neurotrophic signals operating in an autocrine or paracrine manner may regulate SVZa neurogenesis in the adult primate brain.

Angiogenic Proteins↗
PubMed2006

Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone.

The anterior subventricular zone of the adult mammalian brain contains progenitor cells which are upregulated after cerebral ischemia. We have previously reported that while a part of the progenitors residing in adult monkey anterior subventricular zone travels to the olfactory bulb, many of these cells sustain location in the anterior subventricular zone for months after injury, exhibiting a phenotype of either neural or neuronal precursors. Here we show that ischemia increased the numbers of anterior subventricular zone progenitor cells expressing developmentally regulated transcription factors including Pax6 (paired-box 6), Emx2 (empty spiracles-homeobox 2), Sox 1-3 (sex determining region Y-box 1-3), Ngn1 (neurogenin 1), Dlx1,5 (distalless-homeobox 1,5), Olig1,3 (oligodendrocyte lineage gene 1,3) and Nkx2.2 (Nk-box 2.2), as compared with control brains. Analysis of transcription factor protein expression by sustained neural or neuronal precursors in anterior subventricular zone revealed that these two cell types were positive for characteristic sets of transcription factors. The proteins Pax6, Emx2, Sox2,3 and Olig1 were predominantly localized to dividing neural precursors while the factors Sox1, Ngn1, Dlx1,5, Olig2 and Nkx2.2 were mainly expressed by neuronal precursors. Further, differences between monkeys and non-primate mammals emerged, related to expression patterns of Pax6, Olig2 and Dlx2. Our results suggest that a complex network of developmental signals might be involved in the specification of primate progenitor cells.

Analysis of Variance↗
PubMed2002

MRI evaluation of the diaphragmal opening: using MRI parallel to the transsphenoidal surgical approach.

Twenty-six adult diaphragma sellae and infundibulae were examined by MRI parallel to the transsphenonidal surgical plane with attention given to the diaphragmal opening. The diaphragmal opening was observed in 11 cases (42.3%). The anteroposterior diame ter of the opening ranged from 4.0 to 14.0 mm (mean 8.8 mm), and the lateral diameter ranged from 6.0 to 14.0 mm (mean 9.5 mm). In the cases of open diaphragma sellae, the infundibulum tended to be located in the posterior part of the diaphragma sellae but this was not statisticallysignificant. On MRI parallel to the transsphenoidal surgical approach, the anatomy of the dia phragma sellae was well evaluated.

Adolescent↗
PubMed2001

Calpain-dependent proteolysis of merlin occurs by oxidative stress in meningiomas: a novel hypothesis of tumorigenesis.

BACKGROUND: The purpose of this study is to indicate that oxidative stress may contribute to occurrence of meningiomas. Recently, it was reported that aside from the neurofibromatosis type 2 (NF2) gene mutations, the calpain-dependent proteolysis of the NF2 gene product, merlin might be closely related to the development of certain NF2-related tumors. Although meningiomas are well known to occur more frequently in aged persons, it still remains unknown why calpain activation occurs predominantly in them. Because the production of free radicals with aging might be one of the causes of calpain activation especially in leptomeningeal cells being devoid of blood supply, the authors examined the relations between mu-calpain activation and merlin proteolysis induced by the oxidative stress. METHODS: The authors examined 12 patient-derived sporadic meningiomas and their primary cultured cells. Malignant glioma cell line (U-251MG), which had no relation to NF2, was used as a control. They were exposed to hydrogen peroxide (H2O2) for 1 hour. After oxidative stress, they were examined by Western blot and immunofluorescence microscopic analyses. RESULTS: Despite the consistent expressions of activated mu-calpain in 11 of 12 meningioma tissues, this calpain activation completely disappeared after culture; instead the full-length merlin appeared again in 8 of 11 cases. The treatment of cultured cells with hydrogen peroxide induced both mu-calpain-dependent cleavage of merlin and reduction of an intrinsic calpain inhibitor calpastatin. Such proteolysis was significantly blocked by a specific calpain inhibitor, Z-LLal. The full-length merlin was immunocytochemically colocalized with activated mu-calpain at the plasma membrane, and, after mu-calpain activation, the fragment of merlin translocated to the perinuclear cytoplasm or into the nucleus. CONCLUSIONS: These findings suggest that oxidative stress-induced activation of mu-calpain causes proteolysis of merlin conceivably to impair cell adhesion and/or contact inhibition of meningioma cells.

Brain Neoplasms↗
PubMed2001

CT during selective arteriography: anatomical assessment of unruptured intracranial aneurysms before endovascular treatment.

Our aim was to investigate the usefulness of helical CT during selective angiography (CT arteriography) in pretreatment assessment of unruptured intracranial aneurysms. We studied 47 unruptured aneurysms in 34 prospectively recruited patients for whom endovascular embolisation was initially considered. As pretreatment assessment, we performed rotational digital subtraction angiography (DSA) followed by CT arteriography. The findings on axial source images (axial images) and reconstructed three-dimensional CT angiography (3D-CTA) of CT arteriography were compared to those of rotational DSA, with particular attention to the neck of the aneurysm and arterial branches adjacent to it. Information provided by CT arteriography was more useful than that of rotational DSA as regards the neck in 25 (53%) of 47 cases and as regards branches in 18 (49%) of 37 aneurysms. On axial images, small arteries such as the anterior choroidal artery were seen in some cases. CT arteriography can provide valuable additional information about unruptured aneurysms, which cannot be obtained by rotational DSA alone. This technique is useful for obtaining anatomical information about aneurysm anatomy and for deciding the therapeutic strategy.

Adult↗
PubMed2001

Prostaglandin D synthase (beta-trace) in meningeal hemangiopericytoma.

The level of prostaglandin D synthase (PGDS), a major protein constituent of cerebrospinal fluid (CSF), is altered in various brain diseases, including meningitis. However, its role in the brain remains unclear. PGDS is mainly synthesized in the arachnoid cells, the choroid plexus and oligodendrocytes in the central nervous system. Among brain tumors, meningiomas showed intense immunoreactivity to PGDS in the perinuclear region. Thus, PGDS has been considered a specific cell marker of meningioma. In this study, we examined 25 meningeal hemangiopericytomas (HPCs) and found that 16 of the tumors (64%) showed immunoreactivity for PGDS in the perinuclear region. For comparison, 15 meningiomas, 14 soft-tissue HPCs, 1 mesenchymal chondrosarcoma, 3 choroid plexus papillomas, and 7 oligodendrogliomas were also examined. Meningiomas showed positive immunoreactivity for PGDS in 13 cases (80%). Except for one case located at the sacrum, none of the other soft-tissue HPCs showed immunostaining for PGDS. Mesenchymal chondrosarcoma arises in the bones of the skull, and its histological pattern resembles that of HPC; however, it showed no immunoreactivity for PGDS. Neither choroid plexus papillomas nor oligodendrogliomas were immunopositive for PGDS. These findings suggest that meningeal HPCs may have a unique molecular phenotype that is distinct from that of the soft-tissue HPCs. The origin of meningeal HPCs may be more closely related to the arachnoid cells.

Adolescent↗
PubMed2001

Implications of CAD and DNase II in ischemic neuronal necrosis specific for the primate hippocampus.

The exact molecular mechanism of ischemic neuronal death still remains unclear from rodents to primates. A number of studies using lower species animals have suggested implication of apoptosis cascade, while using monkeys the authors recently claimed necrosis cascade by calpain-induced leakage of lysosomal cathepsins (calpain-cathepsin hypothesis). This paper is to study implications of apoptotic versus necrotic cascades for the development of hippocampal CA1 neuronal death in the primate brain undergoing complete global ischemia. Here, we focused on two terminal cell death effectors; caspase-activated DNase (CAD) and lysosomal enzyme DNase II, in the monkey CA1 sector undergoing 18 min ischemia. The expressions of their mRNA and proteins, and the subcellular localizations as well as ultrastructure and specific DNA gel electrophoresis were examined. Expression of CAD was much less in the normal brain, compared with the lymph node or heart tissues. On day 1 after ischemia, however, CAD mRNA and protein were significantly increased in the CA1 sector, and then CAD protein immunohistochemically showed a translocation from the perikarya into the nucleus. Activated DNase II protein was significantly increased on days 2 and 3 after ischemia, and also showed a similar translocation indicating lysosomal leakage. Although the post-ischemic CA1 neurons showed positive terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining on days 3-5, they showed eosinophilic coagulation necrosis on light microscopy, and frank membrane disruption and mild chromatin condensation on electron microscopy. Furthermore, DNA smear pattern typical for necrosis was observed instead of DNA laddering. These data altogether suggest that the post-ischemic CA1 neuronal death of the monkey occurs not by apoptosis but by necrosis with participations of lysosomal enzymes DNase II and cathepsins as well as CAD. The interactions between apoptotic (caspase-3 and CAD) and necrotic (calpain, cathepsin and DNase II) cascades should be studied further.

Actins↗
PubMed2001

Neuroprotective effects of pyridoxal phosphate and pyridoxal against ischemia in monkeys.

Previously, in monkeys undergoing 20 min whole brain ischemia we demonstrated that the activated calpain-induced lysosomal disruption with the resultant leakage of cathepsins B and L, causes neuronal death in the cornu Ammonis (CA) 1 sector on day 5. Selective cathepsin inhibitors significantly protected ischemic CA1 neurons from delayed necrosis. Recently, pyridoxal phosphate (PLP) and pyridoxal (hydrochloride) (PL) were demonstrated to inhibit cathepsins B and L in vitro, because the active aldehyde at position 4 of the pyridine ring has an affinity for the active site -SH of cysteine residues of cathepsins. Here, we studied whether PLP and PL can, in vivo, protect monkey CA1 neurons from ischemic insult. In monkeys undergoing 20 min whole brain ischemia, 15 mg/kg body weight/day of drugs were intravenously injected for 10 days before and after the ischemic insult. Histological analysis of the surviving CA1 neurons was done using the hippocampus resected on day 5 after ischemia. For PLP or PL, approximately 17% (P = 0.0639) or 54% (P < 0.0001) of the total population (100%) of control CA1 neurons were, respectively, saved from the ischemia-induced neuronal death, showing a remarkable contrast to the surviving neurons (approximately 3.9%) in non-treated monkeys. These data suggested that PL (perhaps PLP intracellularly) is useful as a novel neuroprotectant in primates.

Animals↗
PubMed2001

Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity.

A series of events initiated by glutamate-receptor interaction perturbs cellular homeostasis resulting in elevation of intracellular free calcium and cell death. Cells subject to such environmental change express stress proteins, which contribute importantly to maintenance of metabolic homeostasis and viability. We show that an inducible chaperone present in endoplasmic reticulum (ER), the 150-kDa oxygen-regulated protein (ORP150), is expressed both in the human brain after seizure attack and in mouse hippocampus after kainate administration. Using mice heterozygous for ORP150 deficiency, exposure to excitatory stimuli caused hippocampal neurons to display exaggerated elevation of cytosolic calcium accompanied by activation of mu-calpain and cathepsin B, as well as increased vulnerability to glutamate-induced cell death in vitro and decreased survival to kainate in vivo. In contrast, targeted neuronal overexpression of ORP150 suppressed each of these events and enhanced neuronal and animal survival in parallel with diminished seizure intensity. Studies using cultured hippocampal neurons showed that ORP150 regulates cytosolic free calcium and activation of proteolytic pathways causing cell death in neurons subject to excitatory stress. Our data underscore a possible role for ER stress in glutamate toxicity and pinpoint a key ER chaperone, ORP150, which contributes to the stress response critical for neuronal survival.

Animals↗
PubMed2001

Serial neuroimaging of a growing thrombosed giant aneurysm of the distal anterior cerebral artery--case report.

An 81-year-old female presented with a giant aneurysm of the distal anterior cerebral artery (A3) which grew from a small saccular aneurysm to a huge aneurysm within 36 months before manifesting as a mass lesion. The thrombosed portion of the aneurysm showed growth, whereas the aneurysmal cavity did not change in size. Computed tomography and magnetic resonance imaging showed new bleeding in the thrombosed portion. Hemorrhage into the thrombus and/or aneurysmal wall might have caused the aneurysmal growth. She refused surgery and was discharged with no deficits. Distal anterior cerebral artery aneurysm which shows neuroimaging signs of growth requires regular follow up as such lesions may become giant before manifesting clinical symptoms.

Aged↗
PubMed2000

Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates.

Although more than 8000 papers of apoptosis are published annually, there are very few reports concerning necrosis in the past few years. A number of recent studies using lower species animals have suggested that the cornu Ammonis (CA) 1 neuronal death after brief global cerebral ischemia occurs by apoptosis, an active and genetically controlled cell suicide process. However, the studies of monkeys and humans rather support necrosis, the calpain-mediated release of lysosomal enzyme cathepsin after ischemia conceivably contributes to the cell degeneration of CA1 neurons. This paper provides an overview of recent developments in ischemic neuronal death, presents the cascade of the primate neuronal death with particular attentions to the cysteine proteases, and also indicates selective cathepsin inhibitors as a novel neuroprotectant. Furthermore, the possible interaction of calpain, cathepsin, and caspase in the cascade of ischemic neuronal death is discussed.

Animals↗
PubMed2000

Increased expression of deoxyribonucleic acid methyltransferase gene in human astrocytic tumors.

The relationship between the grade of astrocytic tumor and the expression of deoxyribonucleic acid methyltransferase (DNA-MTase) gene was examined. The levels of DNA-MTase messenger ribonucleic acid (mRNA) were measured by semiquantitative reverse transcriptase-polymerase chain reaction in surgical specimens from 12 astrocytic tumors (4 astrocytomas, 6 anaplastic astrocytomas, and 2 glioblastomas) and two normal brain tissues, and in four glioma cell lines. Compared to normal brain tissues, the levels of DNA-MTase mRNA were increased by 16- to 55-fold in low grade astrocytomas, and significantly increased by 200- to 4500-fold in high grade astrocytomas (anaplastic astrocytomas and glioblastomas) and more than 4500-fold in glioma cell lines. In situ hybridization with paraffin-embedded surgical specimens of human astrocytic tumors showed DNA-MTase mRNA was abundantly expressed in high grade astrocytomas. The detection of increased DNA-MTase expression in astrocytic tumor indicates involvement in the tumorigenesis and suggests that blocking of this change with specific inhibitors may offer new therapeutic strategies for malignant astrocytic tumors.

Astrocytoma↗
PubMed2000

Ruptured irregularly shaped aneurysms: pseudoaneurysm formation in a thrombus located at the rupture site.

OBJECT: The authors describe the clinical, radiological, and pathological findings of ruptured cerebral aneurysms with irregular configurations. METHODS: Eight patients with subarachnoid hemorrhage due to ruptured irregularly shaped aneurysms were examined. The preoperative radiological findings in these cases were compared with the pathological and operative findings of endovascular or open surgery. All of the aneurysms exhibited delayed opacification and delayed washout of contrast medium from the irregularly shaped portion of the aneurysm on digital subtraction angiography and/or helical computerized tomography scanning. Endovascular embolization with platinum coils was attempted in the first four patients who underwent treatment. In three of these patients the aneurysm ruptured again during the endovascular procedure. In the fourth patient an intraaneurysm thrombus was observed during the procedure and clipping was performed. In the subsequent four patients, three underwent clipping without complication and one underwent partial aneurysm embolization because of poor general status. A thrombus adjacent to the aneurysm dome was observed in the patients who underwent open surgery. Pathological examination of the operative specimens revealed a pseudoaneurysm-like cavity in the thrombus that was adherent to the aneurysm. CONCLUSIONS: Ruptured irregularly shaped aneurysms may be accompanied by fragile pseudoaneurysm-like cavities located at the rupture point. Because these aneurysms have a high risk of repeated rupture during an endovascular procedure, advancing microinstruments to the weaker portion of the aneurysm should be avoided.

Adult↗
PubMed2000

The inner membrane of chronic subdural hematomas: pathology and pathophysiology.

There is no clear plane between the dura and arachnoid in situ. Instead of the virtual subdural space, there is a dura-arachnoid interface layer, which is structurally the weakest throughout the meninges. An extravasation of blood within the dural border layer splits it, leaving a few tiers of dural border cells over the arachnoid. These cells cover the internal surface of the hematoma, proliferate, and later on, form the inner membrane. The outer membrane is related to hematoma enlargement because of the repetitive hemorrhages whereas the inner membrane is related to liquefaction of the subdural hematoma. As the inner membrane plays a pivotal role in the pathophysiogenesis and determination of the location of chronic subdural hematoma, histologic, ultrastructural, and clinical analyses were performed with correlations to the dura-arachnoid interface and the so-called "subdural space."

Arachnoid↗
PubMed1999

Postictal blockade of ischemic hippocampal neuronal death in primates using selective cathepsin inhibitors.

This paper is to study the participation of cathepsin in ischemic neuronal death of the monkey hippocampal cornu ammonis (CA) 1 sector and also to clarify whether its selective inhibitor epoxysuccinyl peptides such as CA-074 and E-64c can inhibit the neuronal death or not. In the preceding reports, we demonstrated mu-calpain activation and subsequent rupturing of the lysosomal membrane of postischemic CA1 neurons and also increase of enzyme activity of cathepsins B and L in monkeys undergoing a complete 20-min whole brain ischemia. Here, morphological, immunohistochemical and enzymatical analyses were performed to examine the efficacy of two selective cathepsin inhibitors in the postictal blockade of delayed neuronal death in the monkey hippocampus. Both inhibitors could significantly decrease enzyme activities of cathepsins B and L in all hippocampal sectors. When CA-074 was intravenously administered immediately after the ischemic insult, approximately 67% of CA1 neurons were saved from delayed neuronal death on day 5 after ischemia. In contrast, when E-64c was similarly administered, approximately 84% of CA1 neurons were saved from delayed neuronal death on day 5. The surviving neurons showed mild central chromatolysis and negligible immunoreactivity for cathepsins B and L. These observations indicate that the use of cathepsin inhibitors may become novel strategy for prevention of ischemic delayed neuronal death in the primate hippocampus.

Animals↗