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Biomedical subjects

T Morimura

Publications and source records attributed to T Morimura.

At least 73 records · Page 4Linked to original sources

Monocyte subpopulations in human gliomas: expression of Fc and complement receptors and correlation with tumor proliferation.

Cryostat sections of 12 gliomas and of 3 peritumoral brain tissue samples were investigated for mononuclear cell infiltration by immunohistochemistry, concentrating on cells expressing monocyte/macrophage markers. Only low numbers of T cells were detected in the tumors, whereas in average 20%-30% of all cells present in the samples were recognized by various macrophage markers. These cells carried surface epitopes with known function, like Fc-gamma (Fcg) and complement receptors. Microglial cells, in comparison to typical debris laden macrophages, were only recognized by a restricted panel of macrophages markers (anti-Fcg receptors 1, 2, 3, complement receptor CR3, HLA DR, common leucocyte antigen CD45 and the monocyte marker RM3/1). In peritumoral tissue mainly dendritic, microglia-like cells were present, which revealed decreased expression of antigens CD4, RM3/1 and Fcg receptors in comparison to those in gliomas. A significant positive correlation was found between the number of RM3/1 or CR3 (CD11b)-positive cells and the proliferation rate of the tumors as documented by the number of bromodeoxyuridine-positive or Ki-67+ cells.

Antigens, CD↗

Argyrophilic nucleolar organizer region proteins (Ag-NORs) in human brain tumors: relations with grade of malignancy and proliferation indices.

Proliferation indices and mean number of silver-stained nucleolar organizer region-associated proteins (Ag-NORs) are compared in 65 brain tumors, including 34 gliomas, 8 meningiomas, 17 metastatic tumors, and 6 other tumors. Immunocytochemical investigations include labeling with the monoclonal antibody Ki-67 which identifies the whole growth fraction, and with a monoclonal antibody against bromodeoxyuridine (BrdUrd) which detects cells in the S phase of the cell cycle after in vitro incubation with BrdUrd. When all types of tumors are collectively considered, mean numbers of Ag-NORs did not correlate with Ki-67 and Brd-Urd labeling indices (LIs) and mitotic index. Among tumor subtypes, only meningiomas showed significant correlations between Ag-NOR counts, LIs, and malignancy. Mean number of Ag-NORs did not correlate with proliferation indices and tumor grade in low-grade and high-grade gliomas. However, recurrent high-grade gliomas showed a tendency to higher Ag-NOR counts than primary tumors. This study indicates that counting of Ag-NORs in paraffin sections is of limited value in tumor neuropathology. Correlations found in meningeal tumors should be substantiated in larger series.

Adult↗

Prolongation of G1 phase in cultured glioma cells by cis-dichlorodiammineplatinum (II) (CDDP): analysis using bromodeoxyuridine (BrdU)-Hoechst technique.

The cytokinetic response of three murine (AC) and human (GB-1 and GB-2) glioma cell lines to cisdichlorodiammineplatinum (II) (CDDP) was investigated by flow cytometry. Using the 5-bromodeoxyuridine (BrdU)-Hoechst technique, percentages of cultured glioma cells in the various phases of the cell cycle, and relative phase duration were calculated. This technique proved to be a rapid and easily performed method to characterize phase length and transition rate for the complete cell cycle. In the presence of CDDP IC10 (a concentration in which 10% inhibition of cell growth be induced as compared to controls), perturbations of the cell cycle in AC and GB-1 cells included G2 delay or block, decreased transit velocity from G1 to S phase, and prolongation of G1 phase. The mean cell cycle time increased 1.4 times in AC and 1.6 times in GB-1 as compared to controls. In CDDP IC 50-treated GB-2 cells, the mean cell cycle time was prolonged three times longer than control: however, duration of each phase could not be calculated because of significant perturbation of cell cycle. These results suggest that CDDP influences glioma cells at the G1/S boundary and in the G2 phase, resulting in prolongation of the G1 phase and, to a minor degree, in block of the G2 phase.

Animals↗

In situ analysis of cell kinetics in human brain tumors. A comparative immunocytochemical study of S phase cells by a new in vitro bromodeoxyuridine-labeling technique, and of proliferating pool cells by monoclonal antibody Ki-67.

A newly developed in vitro labeling method with bromodeoxyuridine (BrdU) identifies S phase cells in situ in freshly obtained surgical tissue of human brain tumors which is subsequently fixed and embedded in paraffin for BrdU immunovisualization. For the first time, the BrdU labeling index (LI) is successfully compared here with the LI obtained by immunostaining of frozen sections of the same tumors with monoclonal antibody Ki-67 which identifies all proliferating cells, i.e., the growth fraction. LIs were counted in at least five different areas with high density of labeled cells; at least 1,000 cells were counted. In 13 metastatic tumors, Ki-67 LI was 8.3%-62.6%, and BrdU LI was 5.1%-28.0%. In 18 gliomas, Ki-67 LI was 1.4%-19.3%, and BrdU LI was 0.2%-11.6%. In 7 meningiomas, Ki-67 LI was 0.3%-3.0%, and BrdU LI was 0%-2.0%. Statistical comparison of Ki-67 and BrdU LIs by linear regression analysis revealed a highly significant correlation: BrdU LI = 0.99 + 0.34 Ki-67 LI (r = 0.92, P less than 0.001). A significant heterogeneity of proliferation patterns may occur within one sample from area to area, as well as between different samples of the same tumor, especially in gliomas; thus, some subjective influence on LIs by arbitrary sampling and selection could occur in quantitative evaluation of in situ cell kinetics of human brain tumors. This study indicates that our in vitro BrdU-labeling method allows the in situ identification of S phase cells in excellently preserved fixed tumor tissue which is well suited for further histological examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Prurigo pigmentosa successfully treated with minocycline.

Five patients with prurigo pigmentosa were treated with 100-200 mg minocycline daily. The eruption and pruritus rapidly resolved within a few days or up to a week. There has been no recurrence after stopping medication and we conclude that minocycline is effective for prurigo pigmentosa and safer than dapsone.

Adolescent↗

Fibrous xanthoma in the gasserian ganglion: case report.

Occurrence of fibrous xanthoma has been reported increasingly in the skull and the central nervous system, but is extremely rare in the gasserian ganglion. We report on the clinical presentation, radiological appearance, surgical treatment, and histological makeup of a fibrous xanthoma arising from the left gasserian ganglion.

Fibronectins↗

[Effect of CDDP on cultured glioma cell lines: analysis of cell kinetics by flow cytometry].

The cytokinetic response of cultured glioma cell lines to cis-dichlorodiammine platinum (II) (CDDP) was investigated by flow-cytometry using the BUdR-Hoechst technique. By this technique, the percentage of cells in the various components and the relative phase durations were calculated rapidly and simply. In the presence of CDDP ID50, perturbation of the cell cycle was shown and the cell cycle time was prolonged three times longer than in controls in the GB2 cell line. Comparison of histograms obtained at certain time intervals, cell-cycle perturbation by CDDP such as G2-block with prolongation of the S-phase and further G1 accumulation were demonstrated.

Animals↗

Effects of a fructose-rich diet and the aldose reductase inhibitor, ONO-2235, on the development of diabetic neuropathy in streptozotocin-treated rats.

Streptozotocin-diabetic rats were maintained on a 72% fructose diet for 4 weeks and some were treated with an aldose reductase inhibitor (either alrestatin: 0.9 g . kg-1 . day-1 or ONO-2235: 50 mg . kg-1 . day-1). Fructose feeding significantly influenced the development of impaired motor nerve conduction velocity in the diabetic rats and this effect was positively correlated with sorbitol accumulation in the sciatic nerve of diabetic rats maintained on a fructose-rich diet. Treatment with ONO-2235, a new aldose reductase inhibitor, prevented both slowing of motor nerve conduction velocity and elevation of nerve sorbitol concentration. On the other hand, erythrocyte sorbitol levels were significantly correlated to those of the sciatic nerve (r = 0.86, p less than 0.001) and the retina (r = 0.91, p less than 0.001) in these animals. Thus, our findings suggest that increased polyol pathway activity may be related to the pathogenesis of diabetic neuropathy and erythrocyte sorbitol concentrations may prove a useful indicator for the presence of diabetic complications.

Aldehyde Reductase↗

Acromegaly associated with suprasellar and pulmonary hemangiopericytomas. Case report.

The authors report the case of a 35-year-old acromegalic woman who developed amenorrhea and decreased left vision, and who was found to have suprasellar and pulmonary hemangiopericytomas. Total removal of the suprasellar hemangiopericytoma resulted in normalization of the plasma human growth hormone (GH) level and a marked decrease in size of the pulmonary hemangiopericytoma. Immunoperoxidase studies for GH and human hypothalamic growth hormone-releasing factor (GHRF) demonstrated immunoreactive intracellular GH only in the suprasellar hemangiopericytoma, with no immunoreactive intracellular GHRF evident in either the suprasellar or pulmonary hemangiopericytoma.

Acromegaly↗

Potentiation of vincristine effect in human and murine gliomas by calcium channel blockers or calmodulin inhibitors.

The effects of calcium channel blockers and calmodulin inhibitors on vincristine cytotoxicity were studied in vitro with five glioma cell lines: three human glioblastomas, one rat glioma, and one mouse ependymoblastoma. One human glioblastoma and the rat glioma were resistant to vincristine in contrast to other glioma cells. The resistance to vincristine was considerably decreased by nontoxic or marginally toxic concentrations of calcium channel blockers or calmodulin inhibitors, although the former was more effective than the latter. In the presence of verapamil, the vincristine cytotoxicity, as measured by cell doubling times, increased 90- and 84-fold in the vincristine-resistant human glioblastoma and rat glioma, respectively. The decrease in the resistance to vincristine was related to a marked increase in the intracellular level of that drug, probably mediated by inhibiting its outward transport. The in vivo studies showed that verapamil or nicardipine administered daily with vincristine for 10 days significantly enhanced the chemotherapeutic effect of vincristine in an intracranially transplanted rat glioma model. An approximately 32% to 118% increase in life span occurred with 15 mg/kg/day of verapamil, depending on the doses of vincristine.

Animals↗

Effect of selective inhibitor of thromboxane A2 synthetase on cerebral vasospasm after early surgery.

The authors report the results of inhibition of thromboxane A2 synthetase in 49 consecutive patients with subarachnoid hemorrhage (SAH). These unselected Grade I to IV patients all had a ruptured aneurysm of the anterior circle of Willis, and were operated on within 72 hours after SAH. Twenty-seven patients were treated postoperatively by an intravenous infusion of sodium (E)-3- [4-(3-pyridylmethyl)-phenyl] -2- propenoate (OKY-1581), a selective inhibitor of thromboxane A2 synthetase, at 5 micrograms/kg/min for 10 to 14 days, and the remaining 22 patients did not receive this drug. Both groups of patients had similar age distribution and preoperative neurological conditions. A suggestive but statistically insignificant improvement was found in postoperative angiographic vasospasm, ischemic symptoms, and overall outcome in the group receiving OKY-1581. The incidence of low-density areas on the postoperative computerized tomography scans was significantly decreased in patients treated with OKY-1581 infusion.

Acrylates↗

Effect of a new aldose reductase inhibitor, (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) on peripheral nerve disorders in streptozotocin-diabetic rats.

A new aldose reductase inhibitor, (E)-3-carboxymethyl-5-[(2E-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) was administered orally to streptozotocin-diabetic rats (60 mg/kg IV) for 14 days and its effect on motor nerve conduction velocity studied. The compound significantly improved motor nerve conduction velocity of diabetic rats at a minimal dose of 10 mg . kg-1 . day-1 (treated 28.8 +/- 0.5 versus untreated 23.2 +/- 4.7 m/s, p less than 0.01). The sorbitol content of the sciatic nerve and red blood cells measured after 2 weeks was concomitantly reduced in ONO-2235-treated rats (sciatic nerve: 120 +/- 13 versus 595 +/- 146 nmol/g wet weight; red blood cell: 91 +/- 21 versus 165 +/- 39 nmol/g haemoglobin; p less than 0.01 in both 20 mg . kg-1 . day-1-treated versus untreated animals). These results suggest that sorbitol accumulation might contribute to the development of peripheral nerve dysfunction in acutely diabetic animals and the new aldose reductase inhibitor could be a potential drug for therapy of diabetic neuropathy.

Aldehyde Reductase↗

Immunohistochemical study of fibronectin in human glioma and meningioma.

The presence of fibronectin (FN) and glial fibrillary acidic protein (GFAP) in two astrocytomas, 17 glioblastomas, and five meningiomas was studied by indirect immunoperoxidase staining of formalin-fixed and paraffin-embedded surgical specimens. Angiogenesis in tumor was scored by the microscopic angiogenesis grading system (MAGS), and plasma FN levels were measured by single radial immunodiffusion. In astrocytomas and glioblastomas, GFAP-positive tumor cells had no FN expression and FN was confined to proliferating vessel walls and the leptomeninges, showing a mutually exclusive FN and GFAP expression. GFAP-positive tumor cells were occasionally surrounded by a network of FN-positive matrix produced by cells derived from the leptomeninges or blood vessels. In meningiomas, FN expression was found in vessel walls and meningioma cells including whorl formations and psammoma bodies. In general, deep immunoperoxidase staining for FN was shown in the endothelial cells and the psammoma bodies. Plasma FN levels were correlated significantly not to the degree of leptomeningeal proliferation but to the MAGS scores in gliomas.

Astrocytoma↗

ONO-3144, a new anti-inflammatory drug and its possible mechanism of action.

Anti-inflammatory activities of ONO-3144 have been studied in various experimental models. This compound showed an inhibitory effect on increased vascular permeability and acute inflammation. In the carrageenin test the activity of ONO-3144 was comparable to that of indomethacin (IM), while in the dextran, albumin, yeast and scald edema test it was more potent than that of IM. Unlike IM, phenylbutazone (PB) and tiaramide (TI), ONO-3144 showed marked inhibitory effects on H2O2-induced hemolysis and lipid peroxidation. In the prostaglandin (PG) biosynthesis series, ONO-3144 did not inhibit cyclooxygenase activity but stimulated PG hydroperoxidase activity, facilitated conversion to PGH2 and also inhibited thromboxane (Tx) synthetase. The findings suggest that ONO-3144 is potentially a new type of anti-inflammatory drug. Possible sites of action of ONO-3144 are discussed.

Animals↗

[Pineal teratoma--case report (author's transl)].

A 3-year-old boy had a history of nausea and vomiting for 1 month. After two episodes of tonic cramp, he became drowsy and then semicomatous. Physical examination on admission revealed a dehydrated semicomatous boy with fixed, dilated pupils of equal size, horizontal nystagmus, and left hemiparesis with bilateral Babinski signs. Plain skull films showed a separation of coronal and sagittal sutures. A high density area surrounded by cyst was found in the pineal region in CT scan. Angiography demonstrated stretching of the posterior choroidal arteries, backward displacement of the Galen, the posterior mesencephalic and the precentral vein. The right occipital transtentorial approach was selected to remove the tumor totally. Histology revealed epidermis, hair follicle, sebaceus and sweat glands, columar gland, bone, cartilage, muscle, fatty tissue, nervous tissue, and connective tissue, indicating a pineal teratoma. There was no evidence of germinoma.

Brain Neoplasms↗

Plasma membrane structures of medulloblastoma and cerebellar sarcoma.

Three medulloblastomas and 1 cerebellar sarcoma were studied on their plasma membrane structures. The average number of membrane particles per mum2 plasma membrane was 710 on face A and 70 on face B of medulloblastoma and 1280 on face A and 160 on face B of cerebellar sarcoma. The membrane particles were often aggregated in medulloblastoma and diffusely scattered in cerebellar sarcoma. Small gap junctions were occasionally found in cerebellar sarcoma and not evident in medulloblastoma. Round membrane protrusions, about 0.5-0.6 mu in diameter and provided with several small depressions on their foot, were often observed in region of narrow perinuclear cytoplasm of cerebellar sarcoma and different in structure from cytoplasmic processes. The present series is too limited in number to allow a definite conclusion, but indicates that the plasma membrane structures are different in medulloblastoma and cerebellar sarcoma.

Cell Membrane↗