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Masanori Kurimoto, Susumu Ohara, and Akira Takaku

✓ A case is presented of basilar impression secondary to osteogenesis imperfecta tarda, associated with hemifacial spasm and brain-stem compression syndrome. The symptoms improved with posterior fossa decompression and posterior fusion.

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Yutaka Hirashima, Hideo Hamada, Masanori Kurimoto, Hideki Origasa, and Shunro Endo

Object. Increased platelet consumption is expected in patients with cerebral vasospasm, according to data from clinical and experimental studies. The authors investigated sequential changes in platelet counts in patients with subarachnoid hemorrhage (SAH) and the difference in platelet consumption between patients with and those without symptomatic vasospasm (SV). Variables related to platelet count as well as other clinical and radiological variables were analyzed as independent predictors of SV.

Methods. One hundred consecutive patients who had undergone surgery within 48 hours after SAH onset were entered in the study. Clinical and radiological variables and blood cell counts, including red blood cells, white blood cells, and platelets, after SAH were retrospectively examined. Twenty of these variables were entered into univariate and multivariate analyses to determine predictors for SV.

After SAH, the platelet count decreased to a minimum and then increased rapidly to levels greater than those recorded on admission. This change was specific to SAH, and platelet consumption was more severe in patients with SV than in those without. There were three independent predictors of SV: a ratio of the lowest platelet count and the admission count greater than 0.7 (odds ratio [OR] 0.322, 95% confidence interval [CI] 0.124–0.834, p = 0.0196) and a history of hypertension (OR 0.338, 95% CI 0.126–0.906, p = 0.0311) were negatively significant (that is, decreases the occurrence of SV), and a Fisher Grade 3 (OR 4.42, 95% CI 1.48–13.2, p = 0.0077) was positively significant (that is, increases the occurrence of SV).

Conclusions. The association between a decrease in platelet count and the occurrence of SV indicates the important role of platelets in the pathophysiology of vasospasm following SAH.

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Masanori Kurimoto, Yutaka Hirashima, Nakamasa Hayashi, Shunro Endo, Masayoshi Ohi, Soushi Okamoto, and Akira Takaku

✓ The authors report an extremely rare case of neurofibromatosis Type 1 (NF1) with a suboccipital meningocele presenting as a huge retropharyngeal mass. A 73-year-old woman with typical cutaneous manifestations of NF1 presented with nasal obstruction and dysphagia due to a retropharyngeal mass. Magnetic resonance imaging revealed a huge mass lesion extending from the right occipital bone defect to the retropharynx through the right paravertebral region. Computerized tomography scanning after intrathecal administration of contrast material confirmed that the mass was a meningocele protruding through a right occipital bone defect. The authors attempted to ligate this meningocele, most of which was excised via a suboccipital approach, but a second transcervical operation was required. Finally, the meningocele resolved and the patient was discharged without symptoms.

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Shoichi Nagai, Kazuo Washiyama, Masanori Kurimoto, Akira Takaku, Shunro Endo, and Toshiro Kumanishi

Object. It has been suggested that nuclear factor (NF)-κB, a pleiotropic transcription factor, controls cell proliferation. The authors examined NF-κB activity and its participation in the growth of human malignant astrocytoma.

Methods. The authors examined NF-κB activity in human malignant astrocytoma cell lines and high-grade astrocytoma tissues by using electrophoretic mobility shift assays and immunohistochemical studies, respectively. In addition, messenger (m)RNA expression of p50 and RelA, which are representative subunits of NF-κB, and IκBα, which is a representative inhibitory protein of NF-κB, were analyzed using Northern blot hybridization in the astrocytoma cell lines. Furthermore, alterations in DNA synthesis and cell growth in the astrocytoma cell lines were examined after inhibition of NF-κB activity by RelA antisense oligodeoxynucleotide. The authors found NF-κB activity in all astrocytoma cell lines and high-grade astrocytoma tissues that were examined, but not in the fetal astrocyte strain or in normal cerebral tissue. Expression of p50, RelA, and IκBα mRNA was found in the fetal astrocyte strain and normal adult brain tissue, in addition to the astrocytoma cell lines. The relative levels of expression of these mRNAs were similar among these cell lines, the cell strain, and normal tissue. The RelA antisense oligodeoxynucleotide specifically reduced the levels of RelA mRNA expression and NF-κB activity in the astrocytoma cell lines, thus significantly inhibiting their DNA synthesis and cell growth.

Conclusions. Human malignant astrocytoma cells have aberrant NF-κB activity, which promotes their growth. This activity is not associated with aberrant expression of p50 and RelA.

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Masanori Kurimoto, Yutaka Hirashima, Tsuneaki Ogiichi, Hideo Hamada, Hironaga Kamiyama, and Shunro Endo

Object. Patients with neurofibromatosis Type 1 (NF1) have a predisposition to development of a variety of benign and malignant tumors including neurofibromas, astrocytomas, pheochromocytomas, and malignant peripheral nerve sheath tumors. The availability of an astrocytoma cell line derived from NF1 would be useful in studies in which sporadic astrocytomas could be compared with NF1-derived astrocytomas. In this article the authors describe a novel astrocytoma cell line, TM-31, that they established from a tumor removed in a 42-year-old woman with NF1.

Methods. The TM-31 cell line was prepared from a surgical specimen of malignant astrocytoma and was serially subcultured over 250 times throughout a 6-year period without showing any sign of cell senescence. Immunocytochemical analyses demonstrated that TM-31 cells are negative for glial fibrillary acidic protein but positive for vimentin and S-100 protein. The TM-31 cells display little neurofibromin expression when subjected to immunoblotting, indicating that there is an NF1 gene mutation. Polymerase chain reaction—single-strand conformational polymorphism analysis revealed that TM-31 cells harbor a p53 point mutation in exon 7, codon 238. Chemosensitivity testing of TM-31 cells revealed a resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea, although they are sensitive to cisplatin and etoposide. In addition, TM-31 cells displayed no morphological differentiation after all-transretinoic acid and dibutyryl cyclic adenosine monophosphate treatments. Pharmacological inhibition of farnesyltransferase of the Ras oncoprotein led to decreased proliferative activity and inhibition of anchorage-independent growth of TM-31 cells in soft agar.

Conclusions. The TM-31 cell line is an immortalized astrocytoma cell line derived from a tumor obtained in a patient with NF1. Ras activation may be the major event of proliferative activity and of the transformed phenotype of TM-31 cells, and the farnesyltransferase inhibitor may be potentially important as a novel antiproliferative therapy for NF1-derived astrocytomas.

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Yoshifumi Tsuboi, Masanori Kurimoto, Shoichi Nagai, Yumiko Hayakawa, Hironaga Kamiyama, Nakamasa Hayashi, Isao Kitajima, and Shunro Endo

Object

The intrinsic radioresistance of certain cancer cells may be closely associated with the constitutive activation of nuclear factor–kappa B (NF-κB) activity, which may lead to protection from apoptosis. Recently, nonapoptotic cell death, or autophagy, has been revealed as a novel response of cancer cells to ionizing radiation. In the present study, the authors analyzed the effect of pitavastatin as a potential inhibitor of NF-κB activation on the radiosensitivity of A172, U87, and U251 human glioma cell lines.

Methods

The pharmacological inhibition of NF-κB activation was achieved using pitavastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Growth and radiosensitivity assays were performed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Hoechst 33258 staining, supravital acridine orange staining, and electron microscopy were performed utilizing 3 glioma cell lines with or without pitavastatin pretreatment to identify apoptosis or autophagy after irradiation.

Results

The growth of these 3 glioma cell lines was not significantly inhibited by pitavastatin at a concentration of up to 1 μM. Treatment with 0.1 μM of pitavastatin enhanced radiation-induced cell death in all glioma cell lines, with different sensitivity. Apoptosis did not occur in any pretreated or untreated (no pitavastatin) cell line following irradiation. Instead, autophagic cell changes were observed regardless of the radiosensitivity of the cell line. An inhibitor of autophagy, 3-methyladenine suppressed the cytotoxic effect of irradiation with pitavastatin, indicating that autophagy is a result of an antitumor mechanism. Using the most radiosensitive A172 cell line, the intracellular localization of p50, a representative subunit of NF-κB, was evaluated through immunoblotting and immunofluorescence studies. The NF-κB of A172 cells was immediately activated and translocated from the cytosol to the nucleus in response to irradiation. Pitavastatin inhibited this activation and translocation of NF-κB.

Conclusions

Autophagic cell death rather than apoptosis is a possible mechanism of radiation-induced and pitavastatin-enhanced cell damage, and radiosensitization by the pharmacological inhibition of NF-κB activation may be a novel therapeutic strategy for malignant gliomas.

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Nakamasa Hayashi, Hideo Hamada, Kimiko Umemura, Kunikazu Kurosaki, Masanori Kurimoto, and Shunro Endo

Object

Endoscopic third ventriculostomy (ETV) has been widely performed for the treatment of noncommunicating hydrocephalus. In cases of hydrocephalus in conjunction with deformed and complex ventricular anatomy, it is preferable to use a rigid-rod endoscope for ETV, because the excellent visibility provided by this instrument yields a smooth and correct orientation in the ventricle. The authors report on ETV procedures in which they used a transparent endoscopic sheath that has a common channel in which a rigid-rod endoscope and an instrument can be inserted.

Methods

In 15 cases of noncommunicating hydrocephalus, a transparent endoscopic sheath and a rigid endoscope were used for ETV. In 11 of the 15 patients, the diameter of the foramen of Monro and the width of the third ventricle were greater than 5 mm, and thus a transparent endoscopic sheath and a rigid endoscope could be smoothly introduced through the foramen of Monro and an ETV successfully performed. Four patients had congenital or acquired narrowing of the foramen of Monro and an anatomically deformed ventricular system. In three of the patients, opening of the narrowed foramen and an ETV were successfully performed using the transparent endoscopic sheath under direct visualization through the rigid-rod endoscope.

Conclusions

A transparent endoscopic sheath increases safety by offering a corridor to the third ventricle. It also provides excellent visibility without troublesome bleeding from tissues surrounding the foramen of Monro during endoscopic procedures in which a rigid endoscope is used.

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Hideo Hamada, Masanori Kurimoto, Nakamasa Hayashi, Shoichi Nagai, Kunikazu Kurosaki, Kazuhiro Nomoto, Hirokazu Kanegane, Keiko Nomura, and Shunro Endo

✓The authors report on a rare case of pilomyxoid astrocytoma in a patient presenting with fatal hemorrhage. This 5-year-old boy presented to the outpatient clinic with headache and vomiting. Computed tomography and magnetic resonance imaging studies revealed a mass lesion with partial hemorrhage in the suprasellar region extending into the third ventricle. Partial resection via a transcallosal approach was performed. Because the pathological diagnosis was pilomyxoid astrocytoma, chemotherapy was administered. However, 4 months after the first operation, during chemotherapy, the boy presented with massive intratumoral and intraventricular hemorrhage with hydrocephalus. Although emergent external ventricular drainage was performed, the patient died. In this report, the authors review the literature and discuss the clinical features and treatment of pilomyxoid astrocytoma.