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Biomedical subjects

J Kuratsu

Publications and source records attributed to J Kuratsu.

At least 73 records · Page 4Linked to original sources

Intramedullary epidermoid cyst in the brain stem: case report.

BACKGROUND: The incidence of intracranial epidermoid cysts is between 0.2% to 1.8% of all brain tumors. They usually occur in the cerebellopontine angle or parasellar region. Intramedullary epidermoid cyst is rare and only nine cases have been previously reported. METHODS: A 69-year-old woman had progressive left hemiparesis for 2 years. Computed tomography scanning and magnetic resonance imaging (MRI) revealed that there was a cystic tumor in the pons that was compressing the brain stem. A part of the tumor cyst wall and the content of the cyst were surgically removed by right subtemporal transtentorial approach. The histologic diagnosis was epidermoid cyst. After the surgery, the left hemiparesis was improved and there was no sign of the tumor growth by MRI. CONCLUSION: The outcome of the previous cases with radical tumor resection was poor compared with the present case in which only a part of the cyst wall and the content were removed. Therefore, radical removal of the whole tumor may not be necessary for intramedullary epidermoid cyst of the brain stem.

Aged↗

Expression and alternative splicing of Pit-1 messenger ribonucleic acid in pituitary adenomas.

Twenty-eight human pituitary adenomas were analyzed for the expression of Pit-1 messenger ribonucleic acid (mRNA) by using reverse transcriptase-polymerase chain reaction analysis of frozen-section mRNA. Pit-1 mRNA was detected in all functioning tumors and in 9 of 11 nonfunctioning tumors. Pit-1 beta, which is a more active isoform of transcriptional factor for growth hormone than Pit- alpha and which arises from an alternative splicing mechanism, was detected in 14 of 17 functioning tumors and in 5 of 11 nonfunctioning tumors. The transcript that corresponds to Pit-1T, which increases thyroid-stimulating hormone beta promoter activity in rat thyrotropic tumor cells, was not found. There was no significant difference in the total Pit-1 (alpha+beta) mRNA expression level between functioning tumors and nonfunctioning tumors. Growth hormone-producing tumors and other pituitary adenomas also showed no significant difference in the Pit-1 beta/Pit-1 alpha expression ratio. Our data suggest that the major role of Pit-1 gene in pituitary adenoma might not be involved in the regulation of hormone production.

Adenoma↗

Epidemiological study of primary intracranial tumors in childhood. A population-based survey in Kumamoto Prefecture, Japan.

Between 1989 and 1995, we diagnosed primary intracranial neoplasms in 79 children younger than 15 years. All of them belonged to a well-defined population residing in Kumamoto Prefecture, Japan. Of the tumors, 64 (81.0%) were confirmed microscopically. The age-adjusted annual incidence rate was 34.3 cases per million child population. There was a marked difference in the incidence rate between boys (47.1) and girls (22.05). The age-specific annual incidence per million was 24.3 cases for the 0- to 4-year age group, 46.7 for the 4- to 9-year age group and 30.8 for the 10- to 14-year age group. The highest incidence rate was seen in 5- to 14-year-old boys (53.5), the lowest in 10- to 14-year-old girls (7.1). The most common tumors were astrocytomas (41.8%), with an incidence of 14.52 per million, followed by germ cell tumors (15.1%), with an incidence of 6.24 per million, craniopharyngiomas (15.1%), incidence 5.25 per million, ependymomas (6.3%), incidence 2.19 per million, and medulloblastomas (6.2%), incidence 2.19 per million. The distribution of tumor types varied with patient age at the time of diagnosis. Although no germ cell tumors were encountered in the 0- to 4-year age group, in the 10- to 14-year age group, they comprised about one third of all tumors. In contrast, white craniopharyngiomas were rare in the 10- to 14-year age group, they made up more than 22% in the 0- to 4-year age group. In this survey of Japanese children, we found a higher incidence of primary intracranial tumors, especially germ cell tumors and craniopharyngiomas, and a lower incidence of medulloblastomas compared to the incidence reported for Western countries.

Adolescent↗

Epidemiological study of primary intracranial tumors: a regional survey in Kumamoto Prefecture in the southern part of Japan.

This survey consists of 1117 residents of Kumamoto Prefecture who were diagnosed with primary intracranial tumors between 1989 and 1994. Age, sex, tumor type, and date of diagnosis were recorded in all cases; 79% of the diagnoses were confirmed histologically. The overall age-adjusted incidence rate was 9.47 per 100,000 population per year. Among males, the age-adjusted incidence rate was 8.24 per 100,000 per year, and the breakdown included 2.36 gliomas, 1.56 meningiomas, 1.46 pituitary tumors, and 0.99 neurinomas. Among females, the comparable overall rate was 10.7; that included a rate of 3.95 for meningiomas, 2.04 for gliomas, 2.16 for pituitary tumors, and 0.75 for neurinomas. Meningiomas were the most common tumor, with an average annual age-adjusted incidence of 2.76 per 100,000 population. The highest incidence of meniningiomas was 13.02 per 100,000 among women aged 70 to 79 years. The highest incidence of gliomas (5.71 per 100,000 males and 5.29 per 100,000 females) was seen in patients between 60 and 69 years of age. Meningiomas, pituitary adenomas, and malignant lymphomas occurred at a higher rate in females (male/female ratio: 0.39, 0.68, and 0.81, respectively). On the other hand, gliomas, neurinomas, and germ-cell tumors occurred more often in males (male/female ratio: 1.16, 1.32, and 4.29, respectively). Meningiomas and germ-cell tumors tended to exhibit gender specificity.

Adolescent↗

Expression of tissue factor in glioma.

Tissue factor (TF) is a cell surface glycoprotein that initiates the extrinsic coagulation protease cascade and it is expressed in some tumor cells. TF belongs to the interferon receptor family, and it is one of the early immediate genes, suggesting that TF has a biological function other than hemostasis. We investigated the expression of TF in gliomas. Immunocytochemistry showed the expression of TF in 3 glioma cell lines. Immunohistochemical analysis of 44 surgical specimens revealed that all gliomas were positive for TF, and 19 (95%) of 20 glioblastomas, 12 (86%) of 14 anaplastic astrocytomas and 1 (10%) of 10 benign gliomas were moderately or strongly positive for TF. Our study showed that TF is expressed in gliomas, and that the level of TF expression is correlated with the grade of malignancy of the glioma, suggesting that TF may participate in cell growth.

Brain Neoplasms↗

The mechanism of growth-regulation of glioma cells by trapidil.

Trapidil is a PDGF antagonist that can inhibit the proliferation of the PDGF-producing glioma cells, U251MG. As the mechanism of growth-regulation by trapidil remains unclear, we studied its effect on the growth of U251MG cells. We performed a cell cycle analysis and examined the intracellular transduction pathway and oncogene expression in serum-stimulated glioma cells with or without trapidil. After the serum starvation for 3 days, glioma cell proliferation was stimulated by the addition of serum. Cell cycle analysis showed that cell cycle perturbations induced by trapidil included a decreased transition rate from G0-G1 to S phase, suggesting that some metabolic event is required for progress through the G0-G1 phase and that this event is sensitive to trapidil. Internal signal transduction mechanisms are central in the molecular control of cell growth. One such regulator is the protein kinase C(PKC) system and the c-fos gene is likely to be a direct target of intracellular signal transduction pathways. Therefore, we hypothesize that the intracellular PKC activity and c-fos expression of the trapidil-treated cells are suppressed. We posit that trapidil affects the intracellular signal transduction pathway PKC activity and c-fos expression in cells stimulated with serum containing growth factors.

Blotting, Northern↗

Treatment of intracranial nongerminomatous malignant germ cell tumors producing alpha-fetoprotein.

We treated 10 patients with intracranial nongerminomatous malignant germ cell tumors producing alpha-fetoprotein between 1969 and 1992. Two patients were treated with radiotherapy (RT) only (RT group), and three were treated with RT and cisplatin plus vinblastine plus bleomycin therapy with or without surgery (cisplatin plus vinblastine plus bleomycin group). The most recently treated five patients received cisplatin plus etoposide (PE) therapy with or without RT and/or surgery (PE group). The level of alpha-fetoprotein in serum was elevated in all 10 patients. In the PE group, PE therapy consisted of cisplatin (20 mg/m2) and etoposide (60 mg/m2) daily for 5 days (one course) given two or three times at 4-week intervals and then once every 4 months; the patients received three to six courses (mean, 4.2 courses). In the RT group (n = 2), one patient died 3 months after diagnosis and the other died at 12 months. In the cisplatin plus vinblastine plus bleomycin group (n = 3), complete remission was obtained in one patient, but the other two patients died 12 and 24 months after diagnosis. In contrast, in the PE group (n = 5), complete remission was obtained in all patients who are all currently alive without recurrence, at 35 to 71 months (average, 53.6 mo) after diagnosis. The results indicate that multidisciplinary treatment including combination chemotherapy with cisplatin and etoposide with or without surgery and/or RT is highly effective in the treatment of patients with alpha-fetoprotein-producing intracranial nongerminomatous malignant germ cell tumor.

Adolescent↗

Correlation between magnetic resonance images and histology in meningiomas: T2-weighted images indicate collagen contents in tissues.

The magnetic resonance imaging appearance of 40 surgically confirmed intracranial meningiomas was reviewed to correlate signal intensity on T2-weighted images with histological subtypes of meningioma. A moderate variation of signal intensity was found within a given histological subtype. The mean signal intensity scores on T2-weighted images of the fibrous type of meningioma were significantly lower than those of the other types, and were correlated with the collagen content. The signal intensity of meningiomas on T2-weighted images crudely predicts the histological type. Tumors significantly hypointense compared to the cortex are composed primarily of fibrous elements.

Brain↗

Expression of monocyte chemoattractant protein-1 in meningioma.

Monocyte chemoattractant protein-1 (MCP-1), purified from glioma cell line (U-105MG) culture fluid, attracts monocytes but not neutrophils. Macrophage accumulation is one of the pathological features of meningioma. To investigate the mechanism of macrophage infiltration into meningioma, the expression and localization of MCP-1 in 16 cases of meningioma were studied using Northern blot analysis and immunohistochemistry. Seven of 16 meningiomas expressed MCP-1 messenger ribonucleic acid and protein, and some degree of macrophage infiltration was seen in all 16 meningiomas. There was a relationship between MCP-1 expression and the degree of macrophage infiltration; MCP-1 was strongly expressed in meningiomas with a high degree of macrophage infiltration. Sometimes the meningioma was accompanied by perifocal edema; a correlation between macrophage infiltration into brain tumors and perifocal edema has already been reported. It was found that the degree of MCP-1 expression is not correlated with the extent of perifocal edema. The authors' findings suggest that MCP-1 plays an important role in macrophage infiltration into meningioma.

Adult↗

Expression of osteopontin in human glioma. Its correlation with the malignancy.

BACKGROUND: Osteopontin (OPN) is a phosphorylated glycoprotein that contains a functional Gly-Arg-Gly-Asp-Ser (GRGDS) cell-binding sequence. It is reported that the expression of OPN is increased in a number of transformed cell lines. This study demonstrates the expression of OPN in human glioma representative of brain tumors. EXPERIMENTAL DESIGN: The expression of OPN in human gliomas was determined with: (a) Northern blot analysis; (b) Southern blot analysis; (c) Immunofluorescent cytochemistry; (d) Western blot analysis; (e) Cloning and sequencing of complementary DNAs (cDNAS); (f) Immunohistochemistry. RESULTS: OPN mRNA was detected in all glioma cell lines examined, and Southern blot analysis showed that OPN DNA most likely exists as a single copy gene in these cell lines. Immunofluorescent cytochemistry showed strong staining mainly in the cytoplasm. These cell lines produced two major forms of OPN protein migrating at 53 and 47 kilodaltons, and two minor forms at 38 and 31 kilodaltons on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels. We also isolated and sequenced three types of splice variants in OPN from human glioma cell lines through polymerase chain reaction. In addition, Northern blot analysis was carried out on RNA from human astrocytoma tissues of various malignancy grades. Expression of OPN mRNA was high in malignant astrocytomas, but low in benign astrocytomas and non-neoplastic tissue. Immunohistochemistry also showed strong staining in malignant astrocytomas and slight staining in benign astrocytomas. CONCLUSIONS: These findings indicate that OPN mRNA and proteins are expressed in human glioma cells, and that the extent of OPN expression may correlate with the malignancy grade of gliomas.

Alternative Splicing↗

Neurotoxicity and pharmacokinetics of ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in dogs.

Ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a water soluble nitrosourea with log P -0.71, may be efficacious in the treatment of subarachnoid dissemination of malignant glioma. We used 2 dogs to study the neurotoxicity and pharmacokinetics of MCNU. MCNU (1 mg), dissolved in 10 ml of artificial CSF, was administered via the right lateral ventricle during a period of 18 to 42 min and the CSF was drained by lumbar puncture. The perfusion was repeated once a week for 10 consecutive weeks. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord showed local denudation of the ependyma and local subependymal spongy degeneration and gliosis in the lateral ventricle into which MCNU was administered in one dog and local denudation of the ependyma in the other. When administration was over a period of 21 to 38 min, the MCNU concentration in the lumbar CSF peaked at 11.11 to 50.67 micrograms/ml, in 28 to 78 min. The area under the drug concentration-time curve (AUC) was 1152 micrograms x min/ml on average, significantly larger than that of ACNU. The elimination phase followed linear kinetics and the half-time was 41.1 min on average, significantly longer than that of ACNU. These findings suggest that ventriculolumbar perfusion of MCNU may be effective in the treatment of subarachnoid dissemination of malignant glioma notwithstanding some local histological changes.

Animals↗

Mycotic aneurysm accompanied by aspergillotic granuloma: a case report.

Solid granulomas and aneurysms caused by Aspergillus of the central nervous system are rare. A fungal aneurysm is usually situated proximally on the intracranial vessels and is often fatal. We report a case in which a ruptured aneurysm arose from the distal portion of the left posterior inferior cerebellar artery (PICA) in the course of treatment for chronic meningitis forming a granuloma at the left pyramis. After biopsy of the granuloma, he presented subarachnoid hemorrhage caused by a saccular PICA aneurysm. Histologic examination of the aneurysmal wall and the granuloma revealed infection with Aspergillus hyphae. The literature regarding the management of aspergillotic aneurysm is reviewed.

Aneurysm, Infected↗

Malignant trigeminal schwannoma associated with xeroderma pigmentosum--case report.

A 46-year-old male with xeroderma pigmentosum developed an intracranial malignant schwannoma originating from the second branch of the left trigeminal nerve. The tumor was subtotally removed and postoperative radiation therapy given, but the tumor recurred twice over 3 years, and extended to the third branch of the left trigeminal nerve and the ipsilateral facial nerve. Radical surgery and radiation therapy finally achieved a cure. This is the first case of malignant trigeminal schwannoma with xeroderma pigmentosum, although various other internal neoplasms including central nervous system tumors have been reported in xeroderma pigmentosum patients. Radical surgery and radiation therapy are effective for treating intracranial malignant schwannoma. Radiation therapy is considered safe for xeroderma pigmentosum patients.

Cranial Nerve Neoplasms↗

Expression and localization of messenger RNA and protein for monocyte chemoattractant protein-1 in human malignant glioma.

Expression of monocyte chemoattractant protein-1 (MCP-1) in human glioma cell lines and surgical specimens was studied by Northern blot analysis, reverse-transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry. The samples tested consisted of 11 human glioma cell lines and eight specimens of human malignant glioma (seven from glioblastomas and one from a malignant ependymoma). Messenger ribonucleic acid (mRNA) of MCP-1 was detected by either Northern blot or reverse-transcription polymerase chain reaction analysis in all cell lines and tumor specimens examined. In vivo expression of MCP-1 mRNA and protein was found predominantly in glioma cells with large and pleomorphic nuclei rather than in areas of small nucleated glioma cells. Adjacent brain tissue did not produce a significant level of MCP-1 mRNA or protein. Tumor vessels with endothelial proliferation expressed a moderate level of MCP-1 protein. Macrophages were found among the glioma cells, and the degree of macrophage infiltration was grossly correlated with the level of MCP-1 expression. The study results suggest that MCP-1 produced by the glioma cells may mediate macrophage infiltration into the glioma tissue.

Aged↗

Tumor-derived monocyte chemoattractant protein-1 induces intratumoral infiltration of monocyte-derived macrophage subpopulation in transplanted rat tumors.

By immunohistochemistry using anti-rat macrophage monoclonal antibodies RM-1, ED1, ED2, ED3, TRPM-3, and Ki-M2R, we studied transplanted rat tumors of 9L (rat gliosarcoma), Ad-2 (rat mammary carcinoma), and MT-P (rat malignant fibrous histiocytoma) cell lines to examine the distribution pattern of macrophages within and around the tumors. Most tumor-associated macrophages expressed RM-1, ED1, and Ia antigens, indicating activated macrophages. Based on differences in their immunophenotypical expression, these macrophages were distinguished into two major subpopulations. One expressed TRPM-3 and/or ED3, and the other was positive for ED2 and Ki-M2R. The former was considered to be monocyte-derived macrophages, whereas the latter showed the immunophenotype of tissue-fixed, resident macrophages. Infiltration and distribution patterns in the two macrophage subpopulations differed in the three different tumors. Monocyte-derived, activated macrophages infiltrated into 9L- and Ad-2-transplanted tumors, which markedly produced monocyte chemoattractant protein-1 (MCP-1). Additionally, numerous ED2- and Ki-M2R-positive macrophages were observed within the Ad-2-transplanted tumors, and some of them expressed TRPM-3. However, there were few macrophages in the MT-P-transplanted tumors that showed no MCP-1 production. In transplanted tumors of four MT-P/MCP-1 cell lines established by transfecting a rat MCP-1 gene expression vector (pCEP4/MCP-1) into the MT-P cell line, different levels of MCP-1 production were detected, which correlated well with the numbers of intratumorally infiltrated TRPM-3-positive macrophages. In contrast, ED2- and Ki-M2R-positive macrophages were not detected in any MT-P/MCP-1-transplanted tumors. MT-P/MCP-1-transplanted tumors exhibited lower growth rate than parental MT-P-transplanted tumors. These results indicate that tumor-derived MCP-1 induces intratumoral infiltration of monocyte-derived macrophages, but not macrophages with the immunophenotype of tissue-fixed, resident type. The former population of macrophages seems to have a suppressive effect on the growth of tumors.

Animals↗

[Chemotherapy of brain tumors].

Despite recent attempts to improve chemotherapeutic approaches for the treatment of malignant gliomas, results remain limited and palliative. The development of effective chemotherapy for tumors of the central nervous system (CNS) is complicated in that the blood-brain barrier (B.B.B.) hampers the penetration of most drugs into the brain and cerebrospinal fluid. The factors governing delivery in the brain are the drug's molecular weight, lipophilicity and degree of ionization. Now the standard therapy for malignant glioma is maximal tumor resection followed by combination radiotherapy plus chemotherapy. Nitrosoureas are representative drugs which easily cross the B.B.B.. It has been shown that nitrosourea compounds have an additive effect to radiotherapy. The toxicity profile of nitrosoureas is leukocytopenia and thrombocytopenia as a dose-limiting factor. Furthermore, the great heterogeneity of malignant glioma tissues offered a rationale for the use of multiple drugs. Many studies were reported to show a substantial advantage for the multidrug regimen over control series utilizing single drugs alone. Despite clear examples of the effectiveness of chemotherapy, we are still far from improving the cure rate for the vast majority of patients with primary malignancies of the CNS. Further improvement in patient survival may depend upon understanding and manipulating the pathways that regulate aberrant growth in these tumors. The development of new anticancer agents, which are sensitive to malignant glioma and can reach a high concentration in glioma tissue, is warranted.

Blood-Brain Barrier↗

Quantitative study of monocyte chemoattractant protein-1 (MCP-1) in cerebrospinal fluid and cyst fluid from patients with malignant glioma.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a 76-amino acid protein that attracts monocytes. In vitro studies have reported high levels of MCP-1 messenger RNA expression, as well as the presence of MCP-1, in malignant glioma cells. PURPOSE: Our purpose was to determine whether an MCP-1 assay could be used in a clinical setting 1) to differentiate malignant from benign gliomas and from nontumor disorders of the central nervous system and 2) to detect subarachnoid dissemination of glioma cells. METHODS: MCP-1 levels in cerebrospinal fluid (CSF) and cyst fluid were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) that we had previously developed. We measured MCP-1 levels in CSF samples from 19 patients with malignant glioma (glioblastoma, 10; anaplastic astrocytoma, six; anaplastic oligodendroglioma, two; and ependymoblastoma, one), nine patients with benign glioma, and seven patients with nontumor disorders of the central nervous system. Cyst fluids from four patients with malignant glioma (anaplastic astrocytoma) were also tested. The correlation between MCP-1 concentration in the CSF and subarachnoid dissemination of malignant glioma cells was also studied. RESULTS: The MCP-1 concentration (mean +/- SE) in CSF samples from patients with malignant glioma (2.3 +/- 0.4 ng/mL) was significantly higher than that from patients with benign glioma (0.6 +/- 0.1 ng/mL) (P < .01) or from patients with no tumor (0.5 +/- 0.1 ng/mL) (P < .01). Furthermore, CSF samples from patients with subarachnoid dissemination of malignant glioma contained significantly higher amounts of MCP-1 than those from patients without dissemination (P < .05). Cyst fluids from four of the patients with malignant glioma contained high concentrations of MCP-1. CONCLUSIONS: These results indicate that MCP-1 is produced by malignant glioma in vivo as well as in vitro and suggest that testing for MCP-1 in CSF may be useful in the clinic to differentiate malignant glioma from benign glioma and to detect subarachnoid dissemination of the tumor cells. IMPLICATIONS: The MCP-1 ELISA in CSF may lead to more accurate diagnosis of malignant glioma and detection of subarachnoid dissemination of tumor cells, facilitating selection of patients with these conditions for appropriate therapy.

Adolescent↗

Histochemical study of alkaline phosphatase in primary human brain tumors: diagnostic implications for meningiomas and neurinomas.

Histochemical analysis of frozen, thin sections revealed the distribution of alkaline phosphatase (ALPase) in 47 primary intracranial neoplasms in humans. The cytoplasm of meningioma cells exhibited the strongest ALPase reactivity. Pretreatment of these materials by levamisol indicated that the isozymes of ALPase had the characteristic liver-bone-kidney form. In meningiomas and astrocytomas, there was no particular relationship between ALPase activity and malignancy. In neurinomas, there was weak ALPase reactivity in a few neoplastic cells. These findings are suggestive of diagnostic implications for fibroblastic meningiomas and neurinomas at the light microscopic level.

Alkaline Phosphatase↗