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T Morimura

Publications and source records attributed to T Morimura.

At least 55 records · Page 3Linked to original sources
PubMed1994

Induction of apoptosis in murine ACTH-secreting pituitary adenoma cells by bromocriptine.

Bromocriptine, a dopamine agonist, is now an accepted primary therapeutic agent for patients with prolactinomas and other pituitary adenomas. In this study, we demonstrated that bromocriptine inhibited the proliferation of murine ACTH-secreting pituitary adenoma (AtT-20) cells. In addition, the antitumor activity of bromocriptine was inhibited both by actinomycin D and cycloheximide, suggesting that it was dependent on new RNA and protein synthesis. Interestingly, the results of DNA fragmentation assays and cell cycle analysis clearly demonstrated that bromocriptine induced apoptosis in AtT-20 cells.

Adenoma↗
PubMed1994

bcl-2 gene prevents apoptosis of basic fibroblast growth factor-deprived murine aortic endothelial cells.

Growth factors such as basic fibroblast growth factor (bFGF) have been found to promote the survival and proliferation of endothelial cells. However, the mechanism by which growth factors control the regeneration and degeneration of the endothelial cells remained poorly understood. In this study, we demonstrated that apoptosis of murine aortic endothelial (MAE) cells was induced by deprivation of bFGF but required new RNA and protein synthesis. Furthermore, enforced expression of bcl-2 gene in MAE cells using gene transfer techniques decreased apoptosis induced by deprivation of bFGF. These findings suggest that bcl-2 interferes with a pathway for endothelial cell death that is induced by deprivation of bFGF.

Animals↗
PubMed1994

Tumour necrosis factor-alpha induces an increase in susceptibility of human glioblastoma U87-MG cells to natural killer cell-mediated lysis.

The mechanism by which tumour necrosis factor (TNF)-alpha increases the susceptibility of U87-MG human glioblastoma cells to lysis by natural killer (NK) cells was studied. Treatment with TNF-alpha (100 units ml-1) for 48 h enhanced the susceptibility of tumour cells to lysis by NK cells. Increased susceptibility to lysis was associated with enhanced expression of intercellular adhesion molecule 1 (ICAM-1) and HLA class I antigen. Antisense ICAM-1 oligonucleotide inhibited lysis by NK cells of TNF-alpha-treated tumour cells. In contrast, acid treatment following TNF-alpha treatment increased lysis by NK cells. These findings indicate that TNF-alpha treatment of glioblastoma cells increased their susceptibility to lysis by NK cells, since ICAM-1 up-regulation would have more profound effects on NK susceptibility than would HLA class I antigen up-regulation.

Antigens, Neoplasm↗
PubMed1994

bcl-2 gene enables rescue from in vitro myelosuppression (bone marrow cell death) induced by chemotherapy.

Recent studies have shown that the use of cytokines such as granulocyte colony-stimulating factor (G-CSF) to ameliorate chemotherapy-induced myelosuppression may enhance the viability of tumour cells with functional receptors for these cytokines. In this study, therefore, we used murine bone marrow (BM) cells in an in vitro model in an attempt to determine whether topoisomerase inhibitors (camptothecin, etoposide and doxorubicin) induce myelosuppression (BM cell death) and whether novel treatments other than the administration of G-CSF can be used for rescue from myelosuppression. DNA fragmentation assay, ultrastructural analysis and cell cycle analysis demonstrated that these chemotherapeutic agents induced apoptosis in BM cells. We demonstrated in addition that enforced expression of the bcl-2 gene in BM cells by MPZenNeo (bcl-2) retroviral gene transfer increased resistance to the apoptosis induced by these agents. These findings suggest the possibility that enforced expression of the bcl-2 gene in BM cells using gene transfer techniques may enable rescue from chemotherapy-induced myelosuppression.

Animals↗
PubMed1994

Interferon-gamma induces a decrease in the susceptibility of human glioma cells to lysis by lymphokine-activated killer cells.

We studied the effect that treating two types of glioblastoma cell lines, U-87 MG and U-251 MG, with interferon (IFN)-gamma had on their susceptibility to lysis by lymphokine-activated killer (LAK) cells. We also examined the participation of cell-adhesion molecules and major histocompatibility complex (MHC) class I and II antigens present on the target cells in lysis by LAK cells. Treatment with IFN-gamma (1000 U/ml) for 48 hours resulted in the increased expression of both intercellular-adhesion molecule 1 and MHC class I antigens on tumor cells. In addition, untreated tumor cells expressed neural-cell-adhesion molecules and MHC class II antigens highly, but their expression was not affected by IFN-gamma treatment. These changes in expression were accompanied by a decreased susceptibility to lysis by LAK cells. Treatment with antisense-intercellular-adhesion molecule-1 oligonucleotide further inhibited LAK lysis of target cells, following treatment with IFN-gamma. In contrast, acid treatment of tumor cells after treatment with IFN-gamma increased their susceptibility to lysis by LAK cells. These findings suggest that treatment of glioblastoma cells with IFN-gamma decreased their susceptibility to lysis by LAK cells, and that this decrease in susceptibility is attributable principally to the increased expression of MHC class I antigen on target cells.

Base Sequence↗
PubMed1994

Immunohistochemical differential diagnosis of benign cysts in the central nervous system.

This report concerns the immunohistochemical characterization of 6 cases of thin-walled cysts in the central nervous system (enterogenous cyst, paraphyseal neuroepithelial cyst, Rathke's cleft cyst and arachnoid cyst). Antibodies to glial fibrillary acidic protein (GFAP), S-100 protein, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), keratin (KER) and vimentin (VIM) were used. The enterogenous cyst was positive for KER, EMA and CEA. The neuroepithelial cyst of paraphyseal origin was positive for KER and S-100. The three Rathke's cleft cysts were positive for KER and EMA, but negative for S-100 and CEA, and the arachnoid cyst was positive for EMA and VIM. A unified concept and classification of the types of cysts studied based on immunohistochemical assays are proposed.

Adolescent↗
PubMed1994

Preoperative embolization of meningiomas: its efficacy and histopathological findings.

This report deals with the operative and histopathological findings in 14 meningiomas of 13 patients who were subjected to preoperative embolization. This procedure facilitated the removal of 11 of the 14 tumors and minimized blood loss. In the majority of cases the following histopathological findings were documented: 1) Presence of emboli and thrombi within the tumor and/or dural vessels; 2) associated vascular thrombosis; 3) ischemic changes of the tumor cells; 4) pathologic evidence of infarction with or without inflammatory response, and 5) diffuse or nodular necrosis and surviving tumor cell clusters with an island-like appearance. In two tumors in which the histological diagnosis of typical meningioma was difficult, large necrotic areas comprising over two-thirds of the whole specimens were seen with the naked eye.

Adolescent↗
PubMed1993

Immunostaining for proliferating cell nuclear antigen: its role in determination of proliferation in routinely processed human brain tumor specimens.

Alcohol- and formalin-fixed, paraffin-embedded samples of 71 brain tumors (35 gliomas, 22 metastatic carcinomas, 8 meningiomas and 6 other tumors) were investigated by immunocytochemistry with three different monoclonal antibodies against proliferating cell nuclear antigen (PCNA)/cyclin (19A2; 19F4; PC10). PC10 was found to work best; it is applicable to both alcohol- and formalin-fixed tumor samples. PCNA labeling indices (LIs) were compared in the same tumors with LIs obtained by Ki-67 immunostaining of frozen sections and by in vitro incubation with bromodeoxyuridine (BrdUrd); in the latter preparations, BrdUrd LIs could be compared with PCNA LIs in the very same areas of serial sections. In gliomas, PCNA LIs were 0.7-80.2% (mean 31.7%), in metastases 0-76.0% (mean 47.8%), and in meningiomas 0-53.0% (mean 19.3%). In general, PCNA LIs were highly significantly correlated with Ki-67 LIs (P = 0.0002) and BrdUrd LIs (P = 0.0001). However, when tumor subgroups are considered, only gliomas show a significant correlation with Ki-67 and BrdUrd LIs. Despite this statistical correlation, PCNA expression was out of proportion to proliferation indices as determined by both other methods in almost one third of all brain tumors. Immunocytochemistry for PCNA produces a broad spectrum of staining intensity of labeled nuclei, whose number is dependent upon the sensitivity of the immunocytochemical technique used. Thus, inter-observer and inter-laboratory variabilities in PCNA LI determination may occur. Overlapping of PCNA LIs between tumor subgroups of varying malignancy further limits the informational value for the individual case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Induction of apoptosis in rat somatotrophin-secreting pituitary adenoma cells by bromocriptine.

Bromocriptine, a dopamine agonist, is now an accepted primary therapeutic agent for patients with prolactinomas and other pituitary adenomas. In this study, we demonstrated that bromocriptine inhibited the proliferation of rat somatotrophin-secreting pituitary adenoma (GH1) cells. In addition, the antitumor activity of bromocriptine was inhibited both by actinomycin D and cycloheximide, suggesting that it was dependent upon new RNA and protein synthesis. Interestingly, the results of DNA fragmentation assay and cell cycle analysis clearly demonstrated that bromocriptine induced apoptosis in GH1 cells.

Adenoma↗
PubMed1992

True pulmonary carcinosarcoma (squamous cell carcinoma and chondrosarcoma). A case report.

True pulmonary carcinosarcoma (squamous cell carcinoma and chondrosarcoma) originating in the right lower lobe in a 62-year-old Japanese male is reported. The tumor, measuring 5.5 x 3.5 x 3.5 cm, was markedly necrotic and its apex protruded into the bronchial lumen. Light microscopy showed that the tumor was composed of squamous cell carcinoma with sarcomatous spindle or polygonal cell proliferation and true chondrosarcoma. Immunohistochemically, the cytoplasm of numerous cells of the squamous cell carcinoma component was stained with anti-cytokeratin (PKK 1) and the cytoplasmic membrane with anti-epithelial membrane antigen (EMA). Although sarcomatous regions were stained with anti-vimentin (vimentin) and no tumor cells were reactive for EMA, a few tumor cells were positive for PKK 1. The cytoplasm of numerous chondrosarcoma cells was positively stained for vimentin and S-100 protein. Based on these findings, we concluded that the present tumor was a true carcinosarcoma composed of squamous cell carcinoma with sarcomatous regions and true chondrosarcoma.

Aged↗
PubMed1992

[A case of aneurysm of the peripheral middle cerebral artery presenting putaminal hemorrhage--pitfall in diagnosis].

A case mimicking hypertensive putaminal hemorrhage which was first treated by CT-guided stereotactic aspiration and eventually diagnosed as a sequence of the ruptured aneurysm of the left peripheral middle cerebral artery on postoperative angiography is presented. This 41 old, right-handed, hypertensive female suffered sudden onset of headache and right hemiparesis. Next day hematoma was evacuated by the CT-guided stereotactic aspiration because of progressive deterioration of the consciousness and patient recovered well. Fourteen days after the evacuation when she presented mild right hand weakness and motor aphasia, angiography revealed a saccular aneurysm with broad neck derived from left posterior parietal artery. A neck clipping necessitated an additional anastomosis between superficial temporal artery and distal middle cerebral artery because of parent artery stenosis. Postoperatively she is doing well with slight motor aphasia. Among the typical hypertensive putaminal hemorrhage diagnosed on CT scan, it is stressed that there may be a possibility of ruptured aneurysm situated on the peripheral middle cerebral artery.

Adult↗
PubMed1991

Determination of proliferative activities in human brain tumor specimens: a comparison of three methods.

Proliferative activities were determined in 72 human brain tumors, including 20 metastatic carcinomas, 41 gliomas, 8 meningiomas and 3 hematological tumors. Immunocytochemical techniques included labeling with monoclonal antibody (mAb) to bromodeoxyuridine (BrdU) which identifies S phase cells after previous in vitro BrdU incubation and paraffin embedding of fixed tissue specimens, and with mAb Ki-67 which reacts, in frozen sections, with a nuclear antigen expressed by all proliferating cells. BrdU labeling index (LI), Ki-67 LI and mitotic index (MI) correlated well with histological malignancy. Among the three proliferation indices, Ki-67 LI and BrdU LI were highly significantly correlated. With the exception of hematological malignancies, hyperbaric oxygenation of in vitro BrdU labeling did not significantly increase BrdU LI or depth of BrdU penetration into tissue. This study indicates that in vitro BrdU labeling is a useful alternative to Ki-67 immunolabeling of human brain tumor specimens. By such determination of tumor proliferation, it might be possible to design a more adequate postoperative therapy tailored to patients individually.

Antibodies, Monoclonal↗
PubMed1991

Linear focal elastosis. An ultrastructural study.

We studied an 86-year-old Japanese man with linear focal elastosis. The lesions were asymptomatic yellow striae in the lumbar region, histologically composed of massive, well-demarcated basophilic fibers that stained positively with elastic tissue stains. Electron microscopy revealed fine, reticular or granular electron-dense materials, and elastic fiber microfibril-like materials in the matrix, in addition to numerous mature and immature elastic fibers. These findings suggest that active elastogenesis was occurring in the lesions. The four cases reported so far have the three common features of age, sex, and lesion location.

Actin Cytoskeleton↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗