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Biomedical subjects

T Yamashima

Publications and source records attributed to T Yamashima.

At least 55 records · Page 3Linked to original sources
PubMed1995

In vivo and in vitro evidence for ATP-dependency of P-glycoprotein-mediated efflux of doxorubicin at the blood-brain barrier.

We investigated the role of ATP in the active efflux of doxorubicin (DOX) mediated by P-glycoprotein (P-gp), the multidrug-resistance (MDR) gene product, at the blood-brain barrier. In transient brain ischemic rats prepared with 4-vessel occlusion of vertebral and common carotid arteries for 20 min, a procedure that depleted their brain ATP content to 3% that of normal rats, the estimated permeability coefficient of DOX was increased 17-fold (to 243 +/- 2.5 microL/min/g brain). When the ATP content recovered to a normal level by means of 30-min and 24-hr cerebral recirculation of blood, the permeability coefficient recovered to 14.0 +/- 5.0 and 18.4 +/- 2.3 microL/min/g brain (mean +/- SEM, N = 3-6), respectively, very close to the control permeability (14.3 +/- 1.5 microL/min/g brain). The uptake of DOX by primary cultured brain capillary endothelial cells expressing P-gp at the luminal membrane was increased significantly (up to 2-fold), which correlated well with the decrease of cellular ATP contents caused by treating the cells with metabolic inhibitors. Evidence for the ATP-dependent transport of DOX obtained from the present in vivo and in vitro studies strongly indicates that P-gp in the brain capillaries functions actively as an efflux pump in the physiological state, providing a major mechanism to restrict the transfer of DOX into the brain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Basic fibroblast growth factor may repair experimental cerebral aneurysms in rats.

BACKGROUND AND PURPOSE: To determine whether basic fibroblast growth factor (FGF) can induce proliferative response of endothelial cells and/or smooth muscle cells in aneurysmal lesions, we investigated the effect of the intravenous administration of basic FGF on experimental cerebral aneurysms. METHODS: Cerebral aneurysms were induced in rats by ligation of the unilateral common carotid artery, producing hypertension. Three months later, basic FGF was intravenously injected in two groups of randomly divided rats on days 1, 3, and 5 at two different doses (low dose: 2 micrograms/100 g body wt per day; high dose: 5 micrograms/100 g body wt per day). In a control group, normal saline was similarly injected. The junctions of the anterior cerebral artery (ACA) and the olfactory artery (OA) were examined with a light microscope. Aneurysmal changes were defined as the lesions with discontinuity of the internal elastic lamina in more than half of the outward dilated wall. Depending on whether the smooth muscle cell layer was present in the whole wall, the lesions were divided into two stages: early aneurysmal lesion (whole area) and saccular aneurysm (not totally preserved). RESULTS: The control and the low-dose groups presented no obvious intimal thickening in the intact ACA-OA junctions of both nonligated and ligated sides as well as in the aneurysmal changes. In contrast, in the high-dose group, various degrees of intimal thickening in the wall were detected in 7 of 15 early aneurysmal lesions (P = .019, Fisher's exact test). Immunohistochemistry showed the proliferated cells to be smooth muscle cells. CONCLUSIONS: These results demonstrate that exogenous basic FGF induces the proliferative response of smooth muscle cells in aneurysmal lesions in rats.

Animals↗
PubMed1995

Immunohistochemical alterations of fibronectin during the formation and proliferative repair of experimental cerebral aneurysms in rats.

BACKGROUND AND PURPOSE: To determine whether distributional changes of fibronectin, a factor promoting wound healing, occur during the formation and repair of cerebral saccular aneurysms, we performed immunohistochemical analyses in experimental aneurysms. METHODS: Cerebral aneurysms were induced in rats by both the ligation of the unilateral common carotid artery and induced hypertension. Intimal proliferation in aneurysmal walls was induced by the ligation of the preserved common carotid artery 3 months after the first operation. The distribution of fibronectin was examined by immunohistochemistry in anterior cerebral artery-olfactory artery bifurcations under the following three conditions: normal bifurcations in control rats, early aneurysmal lesions during the aneurysm induction, and aneurysmal lesions with intimal proliferation. Furthermore, the immunohistochemical distributions of type I and IV collagens were examined to evaluate the specificity of fibronectin immunoreactivity. RESULTS: In the normal bifurcations, fibronectin was positive in the subintimal space, the surrounding area of the medial smooth muscle cells, and the adventitial fibrous tissue. In early aneurysmal lesions, linear staining of fibronectin and type I and IV collagens in the subendothelial space disappeared with the loss of the internal elastic lamina. In the intimal proliferation of early aneurysmal lesions, fibronectin was strongly immunostained in the subendothelial space and diffusely immunostained in the widened extracellular space surrounding proliferated cells. In contrast, the stainings of type I and IV collagens were sparse or negative. CONCLUSIONS: Although the present findings regarding dynamic changes of fibronectin distribution do not prove any causality in the process of aneurysm formation and repair, these immunohistochemical changes may constitute the crucial sequela of intimal endothelial damage and its subsequent recovery in cerebral aneurysms.

Animals↗
PubMed1995

Multicentric infantile myofibromatosis in the cranium: case report.

Infantile myofibromatosis is a rare clinical entity characterized by multiple mesenchymal tumors in the neonatal period. We describe a 15-month-old girl with multicentric cranial lesions involving the parietal and occipital bones associated with a single small subcutaneous lesion in the back. Magnetic resonance imaging clearly demonstrated the isointense lesions on T1-, T2-, and proton density-weighted images, which showed marked gadolinium enhancement of the tumors and adjacent dura mater. A histological examination of the resected temporal lesion revealed the myofibroblastic nature of the tumor cells. This is the first description of magnetic resonance features of multicentric infantile myofibromatosis in the cranium, and gadolinium-enhanced magnetic resonance images were useful in showing dural involvement. The importance of recognizing this disorder is emphasized because of its special clinical behavior.

Contrast Media↗
PubMed1994

Temperature-dependent Ca2+ mobilization induced by hypoxia-hypoglycemia in the monkey hippocampal slices.

Mobilization of [Ca2+]i in the monkey hippocampal slices during transient hypoxia-hypoglycemia and KCl-induced depolarization was analyzed by microfluorometric imaging and anti-PIP2 immunohistochemistry. Hypoxia-hypoglycemia provoked the largest [Ca2+]i mobilization of CA-1 temperature-dependently whereas [Ca2+]i mobilization by KCl-induced depolarization occurred independent of the temperature in CA-2. Immunohistochemical analysis of the hippocampus after hypoxia-hypoglycemia showed an increased PIP2 staining preferentially in the perikarya of CA-1 neurons. These data suggest that release of Ca2+ from intracellular stores caused by PIP2 breakdown may induce elevated [Ca2+]i.

Animals↗
PubMed1994

Immunoelectron microscopic localization of E-cadherin in dorsal root ganglia, dorsal root and dorsal horn of postnatal mice.

Sensory neurons and associated glial cells are known to express the cell-cell adhesion molecule E-cadherin. The cellular and subcellular localization of this molecule in the dorsal root ganglion, dorsal root, and spinal cord of postnatal mice was studied by the pre-embedding immunoelectron microscopic labelling technique. In the dorsal root and the superficial layer of the dorsal horn, a subset of fasciculating unmyelinated axons expressed E-cadherin at their axon-axon contacts at all ages studied, and these axons were clustered together and segregated from E-cadherin-negative axons. In contrast, pre-myelinating large-diameter axons in P2 mice as well as myelinated axons in mice from P14 to adulthood were E-cadherin-negative. Glial cells also expressed E-cadherin: In the dorsal root ganglia, all of the satellite cells expressed E-cadherin at contact sites with neurons, other satellite cells, and basal lamina, at all ages studied. In dorsal roots from P14 to adulthood, myelin-forming Schwann cells expressed E-cadherin at the outer mesaxons and the contact sites with basal lamina. Non-myelin-forming Schwann cells occasionally stained for this molecule at contact sites with the plasma membrane of E-cadherin-positive axons and at other sites. These results strongly suggest that E-cadherin plays an important role in the selective fasciculation of a particular subset of unmyelinated sensory fibres, and also in glial cell contacts.

Animals↗
PubMed1994

Immunohistochemical expression of human chorionic gonadotropin and P-glycoprotein in human pituitary glands and craniopharyngiomas.

In order to clarify the cellular origin of craniopharyngiomas, the authors examined the distribution of P-glycoprotein (PGP) and human chorionic gonadotropin (HCG) in five normal adenohypophyses and in 23 craniopharyngiomas using peroxidase immunohistochemistry. The correlation between the expression of PGP in craniopharyngiomas and the recurrence of these tumors was also investigated. A number of pars intermedia cyst-lining cells immunostained positively for anti-PGP antibodies. A small number of adenohypophysial cells were also positive for PGP, but squamous epithelial nests were negative in all samples. However, HCG-beta was consistently demonstrated in adenohypophysial cells, pars intermedia cyst-lining cells, and squamous epithelial nests. In 11 craniopharyngiomas, the apical portion of cuboidal cells and some polygonal cells immunostained positively with anti-PGP antibodies. In four HCG-producing craniopharyngiomas, a large number of tumor cells were immunostained with anti-PGP antibodies, three of which showed a recurrence of cystic tumors. By double labeling, the coexpression of HCG-beta and PGP was demonstrated in these recurrent tumors. Accordingly, it is suggested that craniopharyngiomas produce HCG-like peptides and that craniopharyngiomas are unique squamous neoplasms arising in the sellar region from progenitor cells of a neuroendocrine lineage.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Immunohistochemical study of basic fibroblast growth factor and erythropoietin in cerebellar hemangioblastomas.

This report deals with immunohistochemical studies performed on 21 cases of cerebellar hemangioblastomas. Antibodies against basic fibroblast growth factor, glial fibrillary acidic protein, vimentin, factor VIII, and erythropoietin were used. A considerable number of stromal cells and some endothelial cells were positive for basic fibroblast growth factor in all cases studied. The stromal cells of four cases were positive for erythropoietin; two of these cases were associated with secondary polycythemia. Our data suggest that basic fibroblast growth factor may contribute to angiogenesis in cerebellar hemangioblastomas.

Adolescent↗
PubMed1994

Synthesis of multilamellar phospholipids in meningioma cells.

This report is to demonstrate that specimen pretreated with tannic acid before osmification permits the ultrastructural identification of multilamellar phospholipids in 23 of the 30 meningiomas. The phospholipids very often had a fingerprint-like appearance, and were found within the cytoplasm of meningioma cells, among the plasma membranes and in the extracellular matrices. A preferential ultrastructural localization of multilamellar phospholipids to the glycogen-rich area within the cytoplasm was seen in 5 cases. They were intermingled with glycogen granules, or the latter were precipitated on the phospholipids. It is suggested that glycogen may serve as a source of energy for precursors of phospholipid synthesis in meningioma cells.

Adult↗
PubMed1993

Uptake of drugs and expression of P-glycoprotein in the rat 9L glioma.

Two weeks after the inoculation of 1.5 x 10(5) 9L glioma cells into the rat brain, the uptake of radiolabelled drugs into the brain and the experimental 9L glioma during the first cerebral circulation was measured with a liquid scintillation counter and analyzed by the method of Oldendorf (1970). The expression of P-glycoprotein, which is known to be associated with the efflux of drugs, was also studied, using anti-P-glycoprotein monoclonal antibody, C-219. Furthermore, the ultrastructure of brain capillaries, tumor vessels, and glioma cells was studied by conventional and immunoelectron microscopy. Sucrose (control), the transport of which through the blood-brain barrier is known to be negligible, accumulated to fivefold higher levels in the tumor than in normal brain. Ranimustine (MCNU), 5-fluorouracil (5-FU), and doxorubicin showed little accumulation in the normal brain, whereas nimustine (ACNU) showed an increased accumulation. MCNU and doxorubicin showed negligible accumulation in the glioma cells despite diffusion into the tumor interstitial space. In contrast, ACNU and 5-FU showed an increased accumulation in tumor cells. The accumulation of 5-FU in the cultured 9L glioma cells was decreased by ATP inhibitors or by low temperature. Although both brain capillary endothelial cells and glioma cell membrane were immunohistochemically positive for P-glycoprotein, the tumor vasculature showed low expression of P-glycoprotein. The endothelial cells of tumor vessels ultrastructurally showed increased fenestrations, swelling, and disrupted junctions. Accordingly, it is suggested that hydrophobic drugs such as doxorubicin, being pumped out by P-glycoprotein, do not accumulate in 9L glioma cells as do other lipophilic drugs such as ACNU, or drugs such as 5-FU, which accumulate by a carrier-mediated mechanism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Gliosarcoma of the posterior cranial fossa: MRI findings.

We report the MR findings of a biopsy-proven gliosarcoma of the posterior cranial fossa. Multiple homogeneously enhancing lesions had shaggy margins and broad-based dural attachments, which may reflect the gliomatous and sarcomatous element of this tumour.

Aged↗
PubMed1993

Signal intensity of brain metastases on T2-weighted images: specificity for metastases from colonic cancers.

In this report, we present and discuss the signal intensity of brain metastases from colon cancer on both T1- and T2-weighted images. In five of 6 cases, metastases were seen as markedly hypointense areas on T2-weighted images. This finding should alert one to the possibility of a primary cancer of the colon. Some haemorrhagic metastases from other malignancies also showed marked hypointensity. They usually exhibited hyperintensity on T1-weighted images. A case of colon metastasis was also haemorrhagic, and in this case a hyperintense area was observed on T1-weighted images. The marked hypointense area corresponded to peripheral necrosis and probably some viable tumour. Aetiologically, such hypointensity was not induced by severe fibrosis, calcification or excessive iron deposition.

Adolescent↗
PubMed1993

Spinal cord infarction associated with primary antiphospholipid syndrome in a young child. Case report.

Antiphospholipid antibodies have been reported to occur in ischemic stroke patients, but there have been no previous reports linking these antibodies to spinal cord infarction. A case of spinal cord infarction associated with primary antiphospholipid syndrome in a 6-year-old boy is reported. Magnetic resonance imaging clearly demonstrated marked swelling of the thoracolumbar spinal cord with gadolinium-diethylenetriamine pentaacetic acid enhancement at an acute stage, followed later by cord atrophy. Serological study disclosed positive lupus anticoagulant and immunoglobulin G anticardiolipin antibody. It is suggested that the role of antiphospholipid antibodies as an etiological factor for spinal cord ischemia should be recognized among causes that might have been categorized as either spontaneous spinal cord infarction or myelitis.

Antibodies, Anticardiolipin↗
PubMed1993

[Aneurysmal bone cyst of the sixth cervical spine: case report].

A 19-year-old girl was admitted with a history of difficulty in moving her neck for several years and a sudden onset of neck pain three months before. Plain radiographs of the cervical spine revealed destruction of the left half of the 6th cervical body with an expansive soap-bubble appearance. Neurological examination on admission was within normal limits. The angiography and bone scintigraphy revealed no abnormality. MRI of T1-weighted image showed a cystic lesion with various signal intensities. T2-weighted image demonstrated a hyperintense balloon-like lesion in the vertebral body and left lamina. At surgery, a cystic tumor was fully extirpated by the posterior approach and the bony defect was packed with apatite granules. She was discharged without any neurological deficits. This disease should be considered as one of the etiologies when a patient with difficulty in neck movement is encountered in young generation.

Adult↗
PubMed1992

Immunohistochemical localization of cell adhesion molecule epithelial cadherin in human arachnoid villi and meningiomas.

Cadherins are a family of intercellular glycoproteins responsible for calcium-dependent cell adhesion and are currently divided into four types: epithelial (E), neuronal (N), placental (P), and vascular (V). Since cadherins are known to be indispensable for not only morphogenesis in the embryo but also maintenance of tumor cell nest, we examined the expression of E-cadherin in 31 meningiomas (11 syncytial, 12 transitional, 8 fibroblastic) and 3 arachnoid villi by immunoblot and immunohistochemical analyses. In the immunoblot analysis, E-cadherin was detected at the main band of Mr 124,000 in all of the arachnoid villi, as well as syncytial and transitional types of meningiomas, but not in the fibroblastic type. The immunohistochemical examination showed that E-cadherin was expressed at the cell borders of syncytial and transitional types, but the expression was absent in the fibroblastic type. Immunoelectron microscopy showed that E-cadherin was localized at the intermediate junctions in arachnoid villi, while it was detected diffusely at the cell surface in meningiomas. It is suggested from these data that the expression of E-cadherin might be closely related to the differentiation and organogenesis of meningioma cells.

Arachnoid↗
PubMed1992

P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells.

The expression of a functional P-glycoprotein (P-gp) which pumps drugs out of brain capillary endothelial cells (BCEC) into blood was studied by evaluating the steady-state uptake and efflux of vincristine (VCR) by primary cultured bovine BCEC. The steady-state uptake of VCR was increased in the presence of metabolic inhibitors, and an anti-P-gp monoclonal antibody, MRK16, as well as verapamil and steroid hormones which are known to reverse multidrug resistance in tumor cells. Furthermore, efflux of VCR from BCEC was inhibited by verapamil. By immunohistochemistry, P-gp was localized at the luminal side of the capillary endothelial cells in both gray matter of bovine brain and primary cultured BCEC. These data suggest that P-gp functions as a drug efflux pump at the luminal side of BCEC and regulates the transfer of certain lipophilic drugs from the blood into the brain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗