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Biomedical subjects

J Kuratsu

Publications and source records attributed to J Kuratsu.

At least 109 records · Page 6Linked to original sources

Clinical study of intracranial nongerminomatous germ cell tumors producing alpha-fetoprotein.

We present six patients with intracranial nongerminomatous germ cell tumors that produced alpha-fetoprotein (AFP). Their ages ranged from 8 to 20 years (average, 11.5 years old); two were male and four were female. Four of the tumors originated in the pineal region and two in the suprachiasmatic region. One patient treated with only radiation therapy died within 3 months of admission as a result of intraperitoneal metastasis via a ventriculoperitoneal shunt. Another patient, treated with radiation therapy and intrathecal administration of neocarzinostatin, died after 12 months because of tumor progression and subarachnoid dissemination. Two patients who received radiation and combination therapy with cisplatin, vinblastine, and bleomycin died after 13 and 25 months. The remaining two patients treated with radiation therapy and adjuvant chemotherapy (cisplatin and etoposide) are now alive without recurrence after 16 and 19 months from admission. Adjuvant chemotherapy with cisplatin and etoposide appears to be efficacious in the treatment of intracranial nongerminomatous germ cell tumor.

Adolescent↗

Lymphocytic adenohypophysitis accompanying occlusion of bilateral internal carotid arteries--case report.

A 45-year-old female presented with blurred vision, headache, and abnormal thirstiness. She was not pregnant nor postpartum. She had diabetes insipidus and bitemporal hemianopsia. Radiological evidence suggested a mass arising in the sella turcica with extension into the parasellar and suprasellar regions. Carotid angiography showed occlusions of bilateral internal carotid arteries at the cavernous portions. The mass was subtotally removed by the trans-sphenoidal approach and was histologically diagnosed as an adenohypophysitis. Laboratory data showed the patient to be in an active state of autoimmune disorder and hypopituitarism. When a patient presents with pituitary insufficiency and an enhanced intrasellar mass lesion on computed tomographic scan, lymphocytic adenohypophysitis must be included in the differential diagnosis.

Autoimmune Diseases↗

Brain and skull metastases of hepatic or pancreatic cancer--report of six cases.

Brain and skull metastases from primary hepatic or pancreatic cancer are very rare. The authors describe six cases of metastatic tumors. These are skull (three cases) and brain (one) metastasis of hepatic cancer and brain metastasis (two) of pancreatic cancer. In three hepatic cancer patients, the metastatic lesions were diagnosed before the diagnosis of primary cancer. In these patients, plain skull x-ray showed osteolytic lesions and vascular enlargement. A postcontrast computed tomographic (CT) scan showed an enhanced high-density epidural mass. Angiograms showed a tumor stain fed by abnormal vessels from the external carotid artery. In one patient with a metastatic brain tumor from hepatic cancer, a CT scan showed a high-density mass with hematoma. In one of the brain metastases from pancreatic cancer, a CT scan revealed a cystic, ring-like enhanced lesion in the thalamus. In the other case, a CT scan showed an isodensity mass in the vermis and hydrocephalus. Metastatic tumors from primary hepatic cancer were soft and hemorrhagic, but they were clearly demarcated from the surrounding tissue. In the case of thalamic metastasis, the cyst content was aspirated and an anticancer agent was administered into the cystic cavity. In the other cases, the tumors were totally removed. The outcome was very poor in all cases.

Adenocarcinoma↗

Antiproliferative effect of trapidil, a platelet-derived growth factor antagonist, on a glioma cell line in vitro.

Platelet-derived growth factor (PDGF) is produced by glioma cells. However, there is heterogeneity among glioma cell lines in the production of PDGF. It has been demonstrated that U251MG cells produce a PDGF-like molecule while U105MG cells do not. Trapidil, a specific antagonist of PDGF, competes for receptor binding with PDGF. Therefore, the inhibitory effect of trapidil on the proliferation of glioma cells was investigated in vitro using two glioma cell lines. At 100 micrograms/ml, trapidil significantly inhibited the proliferation of U251MG cells (which produce the PDGF-like molecule). At the same trapidil concentration, the proliferation of U105MG cells (which do not produce the PDGF-like molecule) was not inhibited. The inhibitory effect of trapidil was remarkable on Days 3 and 4 of culture. After 4 days of incubation, the proliferation of U251MG cells was 46% of the control preparation. Trapidil enhanced the antitumor effect of 3-[4-amino-2-methyl-5-pyrimidinyl)ethyl)-1-(2-chloroethyl)-1-nitrosourea (ACNU) against U251MG cells. The enhancing effect was highest on Days 4 and 6 of culture. After 6 days of incubation in the presence of 100 micrograms/ml trapidil and 1 microgram/ml ACNU, the proliferation of U251MG cells was 18% of the control preparation. These findings suggest that trapidil interrupts the autocrine loop at the PDGF and PDGF-receptor level and that combination therapy with trapidil and ACNU may be useful in the treatment of glioma.

Animals↗

Cholesterol uptake by human glioma cells via receptor-mediated endocytosis of low-density lipoprotein.

Low-density lipoprotein (LDL) is a carrier of the cholesterol found in human plasma. Cells utilize cholesterol for membrane synthesis by taking up LDL via receptor-mediated endocytosis. In the present study, interactions of LDL with human malignant glioma cell lines (U-251 MG and KMG-5) were investigated biochemically and morphologically. The LDL, labeled with the fluorescent dyes 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI) and fluorescein isothiocyanate (FITC), was internalized by both cell processes and cell bodies. Reductive methylation of DiI-labeled LDL, which abolishes the ability of the cell to bind to the LDL receptor, prevented the internalization of the cholesterol moiety of LDL. Cellular binding of 125I-LDL to U-251 MG cells at 4 degrees C revealed the presence of a specific saturable-associated receptor (dissociation constant (Kd) approximately 38 micrograms/ml). Endocytic uptake of 125I-LDL or 3H-cholesterol oleate-labeled LDL (3H-LDL) at 37 degrees C demonstrated the cell-associated 125I-LDL and 3H-LDL increase. The intracellular degradation of protein moiety increased linearly with time. Reductive methylation of 3H-LDL led to a remarkable decrease in the cell-associated cholesterol moiety of LDL. The difference in uptake of the cholesterol moiety of LDL between U-251MG cells and KMG-5 cells showed that the U-251MG cells, which proliferate more actively than KMG-5 cells, take up more of the cholesterol moiety of LDL than do the KMG-5 cells. Thus, LDL cholesterol seems to be endocytosed predominantly via the LDL receptor present on the plasma membrane of malignant glioma cells. In addition, for growth, these cells may require large amounts of the cholesterol moiety of LDL.

Brain Neoplasms↗

Purification and amino acid analysis of two human glioma-derived monocyte chemoattractants.

Two chemoattractants for human monocytes were purified to apparent homogeneity from the culture supernatant of a glioma cell line (U-105MG) by sequential chromatography on Orange A-Sepharose, an HPLC cation exchanger, and a reverse phase HPLC column. On SDS-PAGE gels under reducing or nonreducing conditions, the molecular masses of the two peptides glioma-derived chemotactic factor 1 and 2 were 15 and 13 kD, respectively. Amino acid composition of these molecules was almost identical, and differed from other cytokines that have been reported. The NH2 terminus of each peptide was apparently blocked. When tested for chemotactic efficacy, the peptides attracted approximately 30% of the monocytes added to chemotaxis chambers, at the optimal concentration of 10(-9) M. Potency and efficacy were comparable with that of FMLP, which is often used as a reference attractant. The activity was chemotactic rather than chemokinetic. In contrast to their interaction with human monocytes, the pure peptides did not attract neutrophils. These pure tumor-derived chemoattractants can now be compared with attractants produced by normal cells and evaluated for their biological significance in human neoplastic disease.

Amino Acids↗

Production and characterization of human glioma cell-derived monocyte chemotactic factor.

Since infiltration of monocytes into tumors may be mediated by tumor-derived chemoattractants, we characterized the monocyte-chemotactic activity (MCA) produced by glioma cell lines. The amount of MCA in the culture fluid of five lines tested differed by a factor of 25. U-105MG, the best producer, was selected for further study. After cells reached confluence and the medium was changed, MCA was detected by day 3 and remained at comparable levels on days 4 and 5. The molecular mass of MCA was approximately 17 kilodaltons, and the estimated isoelectric point ranged between pI 7 and pI 9. Because of the high constitutive production of MCA by U-105MG, sufficient material can be obtained for complete chemical characterization of this mediator of inflammation.

Brain Neoplasms↗

Growth factors derived from a human malignant glioma cell line, U-251MG.

A human malignant glioma cell line, U-251 Mg, cultured under serum free conditions, was shown to produce a growth factor for BALB/c 3T3 cells (glioma-derived growth factor-1, GDGF-1). The biological activity of GDGF-1 resided in a heat- and acid-resistant protein with a molecular weight (MW) of 25 kDa estimated by gel permeation chromatography. GDGF-1 activity was neutralized by a goat anti-human platelet derived growth factor (PDGF) antibody, indicating that the two factors were immunologically related. Furthermore, U-251 Mg cells constitutively expressed c-sis mRNA. When U-251 Mg cells were stimulated with bacterial lipopolysaccharide, 2 novel growth factors (GDGF-2 and GDGF-3) were produced in addition to the PDGF-like substance. GDGF-2 was determined to be greater than 100 kDa MW and was not neutralized by the goat anti-PDGF antiserum. The biological activity of GDGF-3 was also heat- and acid-resistant with an apparent 14 kDa MW. This factor also did not show any common antigenicity with PDGF. GDGF-2 and GDGF-3 are currently under investigation and evidence as to their natures will be published elsewhere. Our findings with this glioma cell line provide further evidence that inappropriate expression of growth factor-related genes could play important autocrine role(s) in the processes leading to malignant transformation and/or uncontrolled proliferation and may provide a paracrine stimulus for such processes as glioma neovascularization.

Animals↗

Lymphocytic adenohypophysitis: report of two cases.

Two women with lymphocytic adenohypophysitis not related to pregnancy are reported on. In obtaining a differential diagnosis of lymphocytic adenohypophysitis preoperatively, it is useful to note swelling of the anterior hypophyseal tissue and the existence of a posterior pituitary lobe on sagittal sections of magnetic resonance imaging scans. Hypofunction of the anterior hypophyseal gland is more severe in lymphocytic adenohypophysitis than in pituitary adenomas. Marked adhesion of fibrotic pituitary capsule to the dura is a characteristic observation during surgery for lymphocytic adenohypophysitis.

Adenoma↗

[Immunological function in head-injured patients. Relationship with severity of injury and age].

The immunological function of 29 head-injured patients was investigated, with special reference to the relationships between changes in immunity and both severity of head injury and age. The patients were classified according to Glasgow Coma Scale scores (15, 9 to 14, and 3 to 8) and age (under 35, 35 to 65, and over 65 years). T cell subsets (OKT4 and OKT8) and Leu-11a cells were studied by flow cytometry with the use of monoclonal antibody. Lymphocyte stimulation indices were also evaluated. The percentage of OKT4 cells was significantly decreased in the young patients with severe head injury, whereas the percentage of OKT8 cells remained almost within the normal range. Thus, the ratio of OKT4 to OKT8 cells was decreased. The percentage of Leu-11a cells showed no correlation with severity of injury or age. Lymphocyte stimulation indices were reduced in cases of severe head injury. In this study, patients with severe head injury were immunosuppressed, particularly those under age 35.

Adult↗

Choroidal epithelial cyst in the cerebellopontine angle associated with trigeminal neuralgia--case report.

The authors describe the case of a 37-year-old female with a symptomatic epithelial cyst in the cerebellopontine angle, which is extremely rare. The cyst caused trigeminal neuralgia, which completely disappeared following its removal. The histological diagnosis was choroidal epithelial fluid-filled cyst. The wall of the cyst consisted of a single layer of epithelial cells with microvilli and a basement membrane.

Adult↗

[Pharmacokinetics of neocarzinostatin in patients with malignant glioma. Quantitative analysis of tissue concentration].

Because of technical difficulties, the pharmacokinetics of neocarzinostatin (NCS) have not been thoroughly evaluated in patients with malignant glioma. The authors produced anti-NCS antibody by immunizing rabbits with NCS and established a means of quantifying tissue levels of NCS with enzyme-linked immunosorbent assay. In one patient given a bolus injection of 1 mg of NCS intra-arterially, the concentration of drug in neoplastic tissue at 25 minutes (0.1136 micrograms/g) was higher than that in blood at 20 minutes and was retained for a longer period. Rapid entry of NCS into the tumor cavity was observed at 5 minutes. In two postoperative cases, NCS applied topically to the tumor site (50 and 100 micrograms) was retained at high levels (0.2941 and 3.33 micrograms/ml) even after 48 hours, although no NCS was detected in blood after 60 minutes. NCS concentrations as low as 1 microgram/ml demonstrated cytocidal effects, and a delay in tumor growth was observed even at an NCS level of 0.1 microgram/ml, despite the fact that the half-life of NCS is extremely short (3 seconds in serum). Because its cytotoxic effect seems to be very rapid, it appears more important to obtain a high initial NCS concentration than to maintain a constant blood level.

Animals↗

[Uptake and localization of neocarzinostatin in malignant glioma. Experimental study by immunofluorescent staining method].

The authors studied the localization of neocarzinostatin (NCS) in cultured cells and in tumor-bearing rats by means of immunofluorescent staining. Anti-NCS antibody was obtained through immunization of rabbits with NCS. Cellular uptake of NCS was dose-dependent (1.0 to 1000 micrograms/ml) in 9L rat gliosarcoma cells in monolayer. In monolayer cells of 9L, KMG-4 (derived from human glioblastoma), and KMS II (human ependymoma) treated with 1 mg/ml of NCS, drug uptake occurred within a few seconds. Accumulation was much higher in the cytoplasm than in the nucleus and, although nuclear uptake increased slightly over time, there appeared to be no increase in total cellular uptake. Mitotic cells, which were spherical in culture, showed greater intracellular accumulation than other cells. There was no significant difference in uptake among non-mitotic cells. Cells surviving 20 hours of treatment retained accumulation as high as that in killed cells. In KMG-4 monolayers, cytoplasmic and nuclear NCS distribution still differed, whereas 9L monolayers exhibited more even intracellular distribution. In 9L spheroid models treated with 1 mg/ml of NCS, the drug permeated almost all layers within 10 minutes, and at 120 minutes had heavily accumulated in the central necrotic areas. In rats with transplanted brain tumors, NCS selectively accumulated in neoplastic tissues following intra-arterial administration. However, NCS uptake by arterial endothelium was also seen, which suggests the potential for vascular toxicity. The therapeutic value of NCS is discussed in terms of its pharmacokinetic characteristics.

Animals↗

[Possible roles of adhesive factor, stromal fibronectin, and peanut agglutinin receptor in subarachnoid dissemination of brain tumor cells].

It has been demonstrated that neoplastic cell surface constituents affect interactions between tumor cells and their host environments during metastasis. A recently discovered glycoprotein adhesive factor (AF) on the surfaces of brain tumor cells is apparently active in multicellular spheroid formation and is assumed to be involved in the adhesion of brain tumor cells. In addition, it has been documented that the peanut agglutinin (PNA) receptor is a factor in the metastatic potential of cancer cells and that fibronectin (FN) plays a role in the attachment of cancer cells to the basal lamina. The authors measured AF and PNA receptor on the surfaces of human brain tumor cells and FN in the stroma of the brain tumor tissue and found a significant relationship between the frequency of subarachnoid dissemination and the presence of these substances. Their results suggest that AF may be very important in the process of exfoliation or dissociation of brain tumor cells from the original tumor into the cerebrospinal fluid cavity and that stromal FN participates in the attachment of migrating tumor cells to new sites. PNA receptor did not appear to be involved in tumor cell dissemination into the cerebrospinal fluid cavity.

Antigens, Neoplasm↗

[Primary malignant lymphoma in the dura and subdural space along the superior sagittal sinus. Case report].

A 56-year-old male with a 11-month history of late-onset epilepsy was hospitalized because of status epilepticus. The physical examination and laboratory data were normal. Neurological examination revealed weakness of the right leg. Coronal computed tomography showed a mass of slightly high density in the bilateral parietal convexity, with homogeneous enhancement by contrast medium. Magnetic resonance imaging disclosed an en-plaque epidural tumor in the parietal region along the superior sagittal sinus, which was normointense on T1- and T2-weighted images. Conventional and digital subtraction angiography showed an avascular mass between the superior sagittal sinus and the inner table of the skull at the parietal region. The mass was thought to be situated in the parietal epidural space. On surgery, however, the tumor was found to be located mainly in the dura and subdural space. The histological diagnosis was malignant lymphoma of the B cell type. Ga-scintigraphy, physical examination, and bone marrow and peripheral blood examinations disclosed no systemic abnormalities. Therefore, the tumor was interpreted as a primary intracranial malignant lymphoma. Reports of primary intracranial malignant lymphoma have been increasing, but most have been located in the cerebrum. The dural-subdural location in this case is evidently rare.

Angiography↗

[Tolosa-Hunt syndrome. Report of a surgical case].

A 58-year-old male presented with painful right ophthalmoplegia and was diagnosed as having Tolosa-Hunt syndrome. High-dose oral administration of a corticosteroid provided significant pain relief, but total ophthalmoplegia persisted. Computed tomography (CT) showed a tumor-like mass in the bilateral cavernous sinus. Angiography revealed occlusion of the right internal carotid artery. According to the literature, about 70% of cases of Tolosa-Hunt syndrome are caused by parasellar neoplasms. A transcranial biopsy of the patient's lesion revealed a nonspecific granulomatous process in the wall of the right cavernous sinus. He was again placed on high-dose corticosteroid therapy and within 1 week the right visual acuity improved slightly. The corticosteroid dose was gradually tapered over 3 months. After 2 months of therapy, the external ocular movement had almost fully recovered, although the light reflex was absent and the CT findings did not change.

Angiography↗