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Biomedical subjects

Y Yoshii

Publications and source records attributed to Y Yoshii.

At least 37 records · Page 2Linked to original sources

[Proliferation inhibition of glioma cells by vitamin K2].

The antitumor effects of vitamin K2 were studied using three glioma cell lines: C6 (rat glioma cell), RBR17T and T98G (human glioma cell). The antitumor effects were estimated by count assay. The results was that vitamin K2 induced growth inhibition in a dose-dependent manner. The RBR 17T cells exposed to vitamin K2 for 72 hours resulted in oligonucleosomal DNA fragmentation and formed a ladder on agarose gel electrophoresis. Furthermore, the RBR17T cells exposed to vitamin K2 for 24 hours were significantly accumulated in the G0G1 phase of the cell cycle. Those results suggested that vitamin K2 can inhibit the proliferation of cells through the induction of cell cycle arrest and apoptosis for tumor cells. The combined treatment of vitamin K2 with ACNU or 5-FU or INF-beta or 1,25-dihydroxyvitamin D3 enhanced growth inhibition significantly. In conclusion, vitamin K2 can be a useful drug for the treatment of glioma.

Animals↗

Endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction.

Recently a point mutation of guanine to thymine at nucleotide position 1917 in the endothelial nitric oxide synthase (eNOS) gene has been reported to be associated with coronary artery spasm. In addition, a significant association of the 4a/b polymorphism in intron 4 of the eNOS gene with coronary artery disease has been reported. However, the implications of these polymorphisms with respect to acute myocardial infarction (AMI) remain to be established. We conducted a case-control study of 226 patients with AMI and 357 healthy gender- and age-matched control subjects. In the former group, coronary angiograms were evaluated according to angiographic criteria based on the number of diseased vessels (>/=75%) and the number of stenotic lesions (>/=50%). Homozygosity for the Glu-Asp298 polymorphism existed in 5 of 226 patients with AMI (2.2%) but not in any of the 357 control subjects (P=.0085). However, when we evaluated the coronary angiograms of 226 case patients, there was no difference in the number of diseased vessels or the number of stenotic lesions between the patients with this homozygote and those without it. By contrast, there was no evidence of a significant increase in the risk of AMI or the severity of coronary atherosclerosis among individuals with the a/a genotype of the eNOS4a/b polymorphism. Our results imply that patients who are homozygous for the Glu-Asp298 polymorphism may be genetically predisposed to AMI; however, this mutation apparently is not related to the severity of coronary atherosclerosis. Further studies are needed to confirm our results and characterize the molecular mechanisms by which eNOS is involved in susceptibility to AMI.

Case-Control Studies↗

Neutron capture therapy with a new boron-porphyrin compound in the rat 9L glioma model.

Neutron capture therapy with a new boron-porphyrin compound was tested in a rat brain tumor model. Although the concentration of boron in the tumor was too low to elicit a therapeutic effect, prominent histopathologic changes, such as necrosis, congestion and bleeding were observed in the tumors of the rats which were administered the boron neutron capture therapy.

Animals↗

Elevated levels of mortalin expression in human brain tumors.

We have performed immunohistochemical studies of mortalin in normal and tumor human brain sections. In normal brain sections, the expression was seen mainly as being confined to neurons. Normal astrocytes showed undetectable expression of this unique member of the heat shock 70 protein family. Three grades of astrocyte tumors (low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma), however, showed an increasing number of mortalin-positive cells. Other types of brain tumors, such as meningiomas, neurinomas, pituitary adenomas, and metastases, also showed elevated levels of mortalin expression compared to those in the normal brain. Mortalin has earlier been reported to have differential intracellular distribution in normal and transformed cells in vitro. Therefore, we substantiated the present study with immunofluorescence localization of the protein in normal and glioblastoma cells. The observations indicated that the tumors might be expressing a nonpancytosolic mortalin. An increase in number of mortalin-positive cells with malignant progression of brain tumors and its correlation with Ki-67 (a cell proliferation marker)-positive cells further suggested an involvement of nonpancytosolic mortalin(s) in malignant transformation of cells in vivo.

Animals↗

Tumor specific contrast enhancement study of Mn-metalloporphyrin (ATN-10)--comparison of rat brain tumor model, cytotoxic and vasogenic edema models.

ATN-10, Mn-metalloporphyrin, has been developed as a tumor selective contrast agent for magnetic resonance (MR) imaging. To investigate the tumor specificity of ATN-10, we produced three experimental in vivo models; rat bran tumor (9L glioma) model, vasogenic (cold injury) and cytotoxic brain edema (24-hour MCA occlusion) models. The time course of contrast enhancement was compared after intravenous injection of ATN-10 or Gd-DTPA, measuring the signal intensity of the region of interest. After ATN-10 administration, the 9L glioma model showed early (5 min) and delayed (24 hr-) peak enhancement whereas the cold injury model showed only early enhancement and the 24-hour MCA occlusion model did not show significant enhancement. After Gd-DTPA administration, all three models showed similar pattern of only early enhancement. As a contrast agent for MR imaging, ATN-10 showed different behavior than Gd-DTPA in demonstrating the blood-brain barrier disruption and moreover ATN-10 showed selective enhancement in experimental brain tumors.

Animals↗

Isolation of radiosensitive and radioresistant mutants from a medulloblastoma cell line.

Two mutant clones, one radiosensitive (OS-3) and one resistant (OR-5), were isolated from ONS-76 after screening 2400 clones by the replica micro-well technique. These two clones exhibited significantly different radiosensitivity, with D37 values of 4.7Gy in OR-5 and 1.7Gy in OS-3. After gamma irradiation (8Gy), OR-5 exhibited greater G2 arrest than sensitive clone OS-3. Administration of 5mM of caffeine resulted in greater cell killing in OR-5 than in OS-3, with an almost complete release of G2 block. These observations support the notion that the G2 block contributes to the repair process of DNA damage after irradiation. The present results suggest that clones with a large postirradiation G2 block may show a greater reduction in radiosensitivity if the G2 block is released artificially. The study of the mutant clones described herein may provide important clues to the mechanism by which glioma cells acquire radioresistance.

Caffeine↗

Characteristics of neurons with high-frequency discharge in the central nervous system and their relationship to chronic pain. Experimental and clinical investigations.

High-frequency extracellular unitary activity was recorded mainly in the ventral caudal nucleus of the thalamus in chronic-pain patients. These high-frequency discharge (hyperactive) neurons shows three types of discharge pattern with different interval histograms. Some of these hyperactive neurons were suppressed by the administration of a calcium antagonist (nicardipine). In an experimental study, chronic-pain models were made in rats according to the method of Lombard et al. (1979). From these animals, hyperactive neurons were recorded from the contralateral thalamic nuclei, lemniscus medialis. Hyperactive neurons were examined via electrical stimulation of and/or iontophoretic application. The results suggest that there is some relationship to the glutamatergic and GABAergic (probably GABAA) fibers or receptors.

Animals↗

[Transient decrease in the size of an enhanced anaplastic astrocytoma seen on magnetic resonance imaging: a case report].

We report unusual radiographic findings which were seen during the management of a patient with anaplastic astrocytoma. An enhanced region in a gyrus of the right frontal lobe was demonstrated in a 38-year-old woman who had had a generalized seizure. Following treatment with steroid- and osmotherapy, this enhanced region decreased clearly on magnetic resonance imaging (MRI). Six months later, an enhancing mass lesion appeared in the same position. After surgery, this was diagnosed as being an anaplastic astrocytoma. It is speculated that the initial enhancement was caused by transient dysfunction of the blood-brain following the seizure. In this case, the most important radiologic image was a T2-weighted image of MRI which was able to demonstrate the existence of the lesion until the time of its removal by surgery.

Adult↗

[Subependymal tumor with metaplastic bone formation: a case report].

A 26-year-old woman was admitted to our hospital because of headache. CT scan and MRI showed a right subependymal nodule and a left ventricular tumor, neither of which had any enhancement nor were they stained in angiography. Although no skin abnormality was detected, the patient was suspected of tuberous sclerosis. The diagnosis was made because of the subependymal nodule on CT scan and MRI. On June 29, 1995, total removal of a left ventricular tumor was performed by a transcortical approach. Histological sections of this tumor consisted of astrocytic and meningothelial components, containing metaplastic bone formation. Histological diagnosis was dysplastic subependymal tumor. Postoperative course was uneventful. Regrowth of the tumor has not been observed as of now. This case was suspected to involve factors of tuberous sclerosis from a subependymal nodule. However, the ventricular tumor was not diagnosed as a subependymal giant cell astrocytoma.

Adult↗

Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients.

Vascular endothelial growth factor (VEGF) has been investigated as a potent mediator of brain tumor angiogenesis, vascular permeability, and glioma growth. Using a VEGF ELISA, we determined the concentration of VEGF in the sera and tumor extracts of 19 brain tumor patients including glioblastoma, anaplastic astrocytoma, low grade astrocytoma, meningioma, malignant lymphoma, and metastatic brain tumor as well as normal brain. Although VEGF concentration of the serum was not correlated with that of the tissue, VEGF concentrations of glioblastoma cyst fluid were 200-300-fold higher than those of serum in the patients. VEGF concentration in the tumors was significantly correlated with the vascularity measured by counting vessels stained with von Willebrand factor antibody. VEGF protein localized to the cytoplasm of tumor cells and vasculature in gliomas, predominantly in the peripheral microvessel "hot spots" as well as around the necrosis in glioblastomas. VEGF immunopositivities were well reflected with VEGF concentration determined by ELISA. VEGF ELISA demonstrated time-dependent increase of the VEGF concentration in the serum-free conditioned medium of various glioma cell lines. The conditioned medium with high VEGF concentration induced endothelial cell migration. These observations suggest that VEGF represents a useful marker and measurable element of glioblastoma angiogenesis. The measurement of VEGF concentration by ELISA in tumor and tumor cyst fluid may allow for the assessment of vascularity in gliomas.

Adult↗

Separation of B-3 monodesamidoinsulin from human insulin by high-performance liquid chromatography under alkaline conditions.

The separation of human insulin (HI) and related compounds such as A-21 monodesamido HI (A-21DHI) and B-3 monodesamido HI (B-3DHI) was investigated using reversed-phase HPLC and capillary zone electrophoresis (CZE). In the case of HPLC under the usual acidic conditions, whereas A-21DHI was separately eluted, B-3DHI was included in the HI peak. Then it was found that by applying a novel ODS column resistant to alkaline conditions, a good separation of B-3DHI from HI could be achieved using an alkaline eluent, and two peaks corresponding to B-3DHI were eluted in front of the HI peak.

Chromatography, High Pressure Liquid↗

Expression of N-ras gene in gliomas.

Expression of N-ras gene was examined by northern blot analysis in two cases of astrocytoma (grade II), four cases of glioblastoma multiforme (six samples including two recurrent tumors), and normal brain tissues. Expression of N-ras gene was only found in the two recurrent glioblastoma multiforme samples. Southern blot analysis found no significant difference in copy numbers of N-ras gene in pre- and post-recurrence samples. The histological diagnosis of the two recurrent tumors was glioblastoma multiforme at both first recurrent presentation. However, the tumors had progressed during recurrence, because of worsened histological findings, such as increased cellularity, pleomorphism, and vascularity. These tumors recurred at very short intervals. Enhanced expression of N-ras gene by disorder of transcription may be a factor in the progression of glioblastoma multiforme.

Astrocytoma↗

Brainstem arteriovenous malformation with a pedicle aneurysm treated by endovascular surgery and proton-beam radiosurgery--case report.

A 39-year-old male presented with a small pontine hemorrhage and subarachnoid hemorrhage. Angiography showed a small left pontine arteriovenous malformation (AVM) associated with a small aneurysm on the pedicle feeding the AVM. The pedicle aneurysm was occluded by microcoils. The AVM was then treated by proton-beam radiosurgery. Follow-up angiography 2 years later revealed that the AVM had disappeared completely without neurological deficit. The combination of embolization and proton-beam radiosurgery was curative in this patient with a pontine AVM associated with an aneurysm on the feeding artery, showing that these techniques can be used to treat inoperable vascular lesions safely.

Adult↗

Induction of human autologous cytotoxic T lymphocytes against minced tissues of glioblastoma multiforme.

The authors induced autologous cytotoxic T lymphocytes (CTLs) directly from peripheral blood lymphocytes by preparing a coculture of minced tissue fragments of glioblastoma multiforme (GBM) with interleukins-1, -2, -4, and -6 and interferon-gamma in RHAM alpha medium containing 5% autologous plasma for 2 weeks. At the end of this period, the frequencies of CD3+, CD4+, CD8+, and CD16+ lymphocytes were 95% to 99%, 40% to 62%, 37% to 38%, and 0.2%, respectively. The lymphocytes killed 82% to 100% of the GBM cells within 48 hours at an effector-to-target cell ratio of 1.67, whereas in a separate coculture, autologous lymphokine-activated killer (LAK) cells killed only 33% of GBM cells under the same conditions. The lymphocytes showed no cytotoxicity against LAK-sensitive Daudi cells, natural killer-sensitive K562 cells or autologous fibroblasts grown from the brain tumor, although they did show slight cytotoxicities against allogeneic GBM cell lines. These results lead the authors to suggest that the lymphocyte population contains specific CTLs for autologous brain tumor cells and that these CTLs could be effective in adoptive immunotherapy to combat brain tumor.

Adult↗

Cerebral radiation necrosis with accumulation of thallium 201 on single-photon emission CT.

A patient who had previously undergone resection of a malignant glioma followed by radiation therapy was found to have a focus of a high accumulation of thallous chloride Tl 201 on single-photon emission CT scans, suggesting recurrent tumor. Resection of this area was performed and the specimen showed radiation necrosis, including such reactive changes as reactive astrocytes and lymphocytes in the necrotic tissue. This case illustrates a diagnostic pitfall in the use of 201Tl single-photon emission CT for distinguishing radiation necrosis from recurrent tumor in patients treated for malignant glioma.

Brain Neoplasms↗

[Rupture of thoracic aorta due to blunt trauma: a report of three cases].

Three cases of the thoracic aortic rupture due to blunt trauma were successfully treated. All of the cases were young male motorcyclists. The chest X-ray on admission showed either a widened mediastinum or an apical extrapleural cap sign. Ruptures were confirmed by an enhanced CT clearly showing the presence of a psuedoaneurysm and a hematoma around the isthmus of the aorta. One of them was operated upon urgently and others in whom heparin could not be used because of associated injuries were operated upon electively two and three months after the traffic accident, respectively. In two of them, aneurysms were removed and replaced with dacron grafts and in the remaining one, the aneurysm was resected and repaired directly under the femoro-femoral bypass. Post-operative courses were uneventful. They discharged and are doing well after the treatment for associated injuries. In view of the high early mortality of aortic rupture, an early diagnosis and treatment is important. But in the case who has stable hemodynamics and contraindication for heparinization, a delayed operation may be recommended.

Accidents, Traffic↗