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Y Tomono

Publications and source records attributed to Y Tomono.

At least 19 recordsLinked to original sources
PubMed2001

Hypoxia down-regulates endostatin production by human microvascular endothelial cells and pericytes.

Endostatin is a potent anti-angiogenic factor derived from the C-terminal region of collagen XVIII and is implicated in the regulation of physiological and pathological angiogenesis. In this study, reverse transcription-polymerase chain reaction analysis of poly(A+) RNA demonstrated the presence of mRNA for collagen XVIII in human endothelial cells (EC) and pericytes, the very constituents of microvessels wherein angiogenesis takes place. Enzyme immunoassay revealed that both cell types liberated endostatin into culture media and that the endostatin levels were decreased by hypoxia, the principal cause of angiogenesis. Northern and Western blot analyses revealed that while the collagen XVIII/endostatin mRNA levels were invariant between hypoxic and normoxic conditions, the collagen XVIII protein levels in EC and pericytes decreased by hypoxia. Further, exogenously administered intact endostatin was significantly decreased when it was incubated with hypoxic conditioned media of endothelial cells or pericytes, but not with normoxic media. The results suggest that the reduction of autocrine endostatin may take an active part in hypoxia-driven angiogenesis.

Angiogenesis Inhibitors↗
PubMed2001

Quantitative study of fruit flavonoids in citrus hybrids of King (C. nobilis) and Mukaku Kishu (C. kinokuni).

Twenty-four Citrus hybrids of King (C. nobilis) and Mukaku Kishu (C. kinokuni) were examined for their flavonoid profiles of the edible part by reversed-phase HPLC analysis. Two hybrids (G-155 and G-156) contained higher amounts of natsudaidain than their parents, whereas the remainder of the hybrids had a character intermediate between those of King and Mukaku Kishu on the basis of polymethoxylated flavone composition. Principal component analysis revealed the distribution of the hybrids by quantifying 23 flavonoid contents.

Chromatography, High Pressure Liquid↗
PubMed2001

[Congestive heart failure caused by the thyroid stimulating hormone(TSH) secreting pituitary adenoma: report of two cases].

A 42-year-old man and a 31-year-old man with congestive heart failure caused by the thyroid stimulating hormone(TSH) secreting pituitary adenoma were reported. Heart failure was improved after transsphenoidal resection of the pituitary adenoma in each patient. The syndrome of inappropriate secretion of TSH causes hyperthyroidism. Thyroid hormone acts directly on cardiac muscle to increase the stroke volume. Hyperthyroidism itself reduces the peripheral vascular resistance and an elevated basal metabolism which is the basic physiologic change in hyperthyroidism dilates small vessels and reduces vascular resistance. The reduced vascular resistance contributes to increase stroke volume. Thyroid hormone also acts directly on the cardiac pacemakers to be apt to cause tachycardiac atrial fibrillation. These mechanical changes in hyperthyroidism increase not only the cardiac output but also the venous return. The increased blood volume and the shortened ventricular filling time due to tachycardia result in congestive heart failure. TSH secreting pituitary adenoma is a rare tumor, however heart failure is common disease. TSH secreting pituitary adenoma should be taken into consideration in patients with heart failure. The presented cases were very enlightening to understand the relation between brain tumor and heart disease.

Adenoma↗
PubMed2000

Expression of the angiogenic factor thymidine phosphorylase in human astrocytic tumors.

Thymidine phosphorylase (TP) has been implicated as a potent angiogenic factor and a prognostic factor in various human solid tumors. We investigated the expression of TP in a series of human astrocytic tumors using immunohistochemistry, enzyme-linked immunosorbent assay, and reverse transcriptase/polymerase chain reaction (RT-PCR) analysis. A total of 63 astrocytic tumors [27 glioblastomas (GBM), 19 anaplastic astrocytomas (AA), 17 low-grade astrocytomas (LGA)] and 5 normal brain tissues were immunohistochemically stained with antibodies to TP, vascular endothelial growth factor (VEGF), p53, MIB-1, and factor-VIII-related antigen. They were also evaluated for the degree of apoptosis by a ApopTag kit. Ten tumors (5 GBM, 2 AA, 3 LGA) and 3 normal brain tissues were evaluated for their expression of VEGF and TP by RT-PCR analysis. TP was constantly localized in the cytoplasm of astrocytic tumor cells, less intensely in the cytoplasm of vascular endothelial cells, but not in the normal brain. Some of the TP-positive cells were of macrophage origin, but most positive cells were the tumor cells themselves. Vascular density, MIB-1 positivity, p53 positivity, VEGF expression, and the apoptotic index were significantly higher in the TP-positive tumors than in TP-negative tumors. There was a significant correlation between TP and VEGF mRNA expression. In a limited number of glioblastoma cases, the apoptotic index was significantly higher in TP-positive glioblastomas than in TP-negative glioblastomas. In human astrocytic tumors, TP was expressed in the tumor, macrophage, and endothelial cells. TP was a potent angiogenic factor closely associated with cell proliferation and tumor apoptosis.

Antigens, Nuclear↗
PubMed2000

Quantitative study of flavonoids in leaves of citrus plants.

Leaf flavonoids were quantitatively determined in 68 representative or economically important Citrus species, cultivars, and near-Citrus relatives. Contents of 23 flavonoids including 6 polymethoxylated flavones were analyzed by means of reversed phase HPLC analysis. Principal component analysis revealed that the 7 associations according to Tanaka's classification were observed, but some do overlap each other. Group VII species could be divided into two different subgroups, namely, the first-10-species class and the last-19-species class according to Tanaka's classification numbers.

Chromatography, High Pressure Liquid↗
PubMed2000

Tissue factor, osteopontin, alphavbeta3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in human gliomas. VEGF-induced proteins in endothelial cells, tissue factor (TF), osteopontin (OPN) and alphavbeta3 integrin have been implicated as important molecules by which VEGF promotes angiogenesis in vivo. Sixty-eight gliomas were immunohistochemically stained with TF, VEGF, OPN and alphavbeta3 integrin antibody. Twenty-three tumours, six normal brains and nine glioma cell lines were evaluated for their mRNA expression of VEGF and TF by reverse transcription polymerase chain reaction analysis. The data indicated that TF as well as VEGF was a strong regulator of human glioma angiogenesis. First, TF expression in endothelial cells which was observed in 74% of glioblastomas, 54% of anaplastic astrocytomas and none of low-grade astrocytomas, correlated with the microvascular density of the tumours. Double staining for VEGF and TF demonstrated co-localization of these two proteins in the glioblastoma tissues. Second, there was a correlation between TF and VEGF mRNA expression in the glioma tissues. Third, glioma cell conditioned medium containing a large amount of VEGF up-regulated the TF mRNA expression in human umbilical vein endothelial cells. OPN and alphavbeta3 integrin, were also predominantly observed in the microvasculature of glioblastomas associated with VEGF expression. Microvascular expression of these molecules could be an effective antiangiogenesis target for human gliomas.

Brain Neoplasms↗
PubMed2000

Immunohistochemical and ultrastructural study of clinically nonfunctioning pituitary adenomas.

Sixty-five clinically nonfunctioning pituitary adenomas were studied by immunohistochemistry, and 12 cases were also analyzed by electron microscopy. Thirty-nine cases (60%) were immunohistochemically identified as hormone-producing adenomas. Six adenomas produced multiple hormones. Electron microscopy found seven null cell adenomas and five oncocytomas. The oncocytomas had a significantly higher incidence of hormone expression that the null cell adenomas. These results indicate that clinically nonfunctioning pituitary adenomas produce hormones, even though blood hormone levels are normal or low. Furthermore, the evidence of multihormonal production implies that two or more cell lineages including a protein hormone-producing type and a glycoprotein hormone-producing type may exist in the same nonfunctioning pituitary adenoma.

Adenoma↗
PubMed1999

Identification of a novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation.

Histone H3 (H3) phosphorylation at Ser(10) occurs during mitosis in eukaryotes and was recently shown to play an important role in chromosome condensation in Tetrahymena. When producing monoclonal antibodies that recognize glial fibrillary acidic protein phosphorylation at Thr(7), we obtained some monoclonal antibodies that cross-reacted with early mitotic chromosomes. They reacted with 15-kDa phosphoprotein specifically in mitotic cell lysate. With microsequencing, this phosphoprotein was proved to be H3. Mutational analysis revealed that they recognized H3 Ser(28) phosphorylation. Then we produced a monoclonal antibody, HTA28, using a phosphopeptide corresponding to phosphorylated H3 Ser(28). This antibody specifically recognized the phosphorylation of H3 Ser(28) but not that of glial fibrillary acidic protein Thr(7). Immunocytochemical studies with HTA28 revealed that Ser(28) phosphorylation occurred in chromosomes predominantly during early mitosis and coincided with the initiation of mitotic chromosome condensation. Biochemical analyses using (32)P-labeled mitotic cells also confirmed that H3 is phosphorylated at Ser(28) during early mitosis. In addition, we found that H3 is phosphorylated at Ser(28) as well as Ser(10) when premature chromosome condensation was induced in tsBN2 cells. These observations suggest that H3 phosphorylation at Ser(28), together with Ser(10), is a conserved event and is likely to be involved in mitotic chromosome condensation.

Amino Acid Sequence↗
PubMed1999

Specific accumulation of Rho-associated kinase at the cleavage furrow during cytokinesis: cleavage furrow-specific phosphorylation of intermediate filaments.

The small GTPase Rho and one of its targets, Rho-associated kinase (Rho-kinase), are implicated in a wide spectrum of cellular functions, including cytoskeletal rearrangements, transcriptional activation and smooth muscle contraction. Since Rho also plays an essential role in cytokinesis, Rho-kinase may possibly mediate some biological aspects of cytokinesis. Here, using a series of monoclonal antibodies that can specifically recognize distinct phosphorylated sites on glial fibrillary acidic protein (GFAP) and vimentin, phosphorylation sites by Rho-kinase in vitro were revealed to be identical to in vivo phosphorylation sites on these intermediate filament (IF) proteins at the cleavage furrow in dividing cells. We then found, by preparing two types of anti-Rho-kinase antibodies, that Rho-kinase accumulated highly and circumferentially at the cleavage furrow in various cell lines. This subcellular distribution during cytokinesis was very similar to that of ezrin/radixin/moesin (ERM) proteins and Ser19-phosphorylated myosin light chain. These results raise the possibility that Rho-kinase might be involved in the formation of the contractile ring by modulating these F-actin-binding proteins during cytokinesis and in the phosphorylation and regulation of IF proteins at the cleavage furrow.

Cell Division↗
PubMed1999

Expression of P27kip1 and Ki-67 in pituitary adenomas: an investigation of marker of adenoma invasiveness.

Mirroring the ambiguities noted with other endocrine tumours, histology is a poor predictor of the invasiveness of pituitary adenomas. Accordingly, the proteins p27Kip1 (p27) and Ki-67, which respectively block cell-cycle progression and reflect proliferative activity of cells, were studied immunohistochemically in 123 specimens of pituitary adenomas including 57 clinically verified invasive cases. Only Ki-67 had a significant association with invasiveness; only p27 differed significantly between functioning and nonfunctioning adenomas, with a higher frequency of cell labelling in the former. No relationship between Ki-67 and p27 was obtained. Ki-67 detected by MIB-1 is thus an important marker related to the invasive potential of adenomas, and thereby may be helpful in planning postoperative management of patients with pituitary adenomas.

Adolescent↗
PubMed1999

Dumbbell-shaped trigeminal neurinoma in a child.

We experienced a case of solitary trigeminal neurinoma in a 10-year-old boy without stigmata of neurofibromatosis. This boy presented with progressive cerebellar ataxia, right abducens palsy and right hemiparesis. Magnetic resonance images (MRI) demonstrated a tumour extending into both the middle and posterior fossas forming a dumbbell-shaped mass lesion with a size of 35 x 30 x 45 mm. The tumour was successfully removed free of complications by a two-stage operation composed of right subtemporal and suboccipital retromastoid approaches. It is extremely rare for a solitary neurinoma to occur at this site in a child without neurofibromatosis. Surgical approaches in this type of tumour are discussed with a review of the literature.

Child↗
PubMed1999

Acridones as inducers of HL-60 cell differentiation.

Fifteen acridone alkaloids were examined for their activity of induction of human promyelocytic leukemia cell (HL-60) differentiation. HL-60 cells were differentiated into mature monocyte/macrophage by atalaphyllidine (9), atalaphyllinine (12), and des-N-methylnoracronycine (13). The activities of NBT reduction, nonspecific esterase, and phagocytosis, were induced by 2.5 microM of 9, 12, and 13. After a 4-day treatment, 9, 12, and 13 at 10 microM inhibited clonal proliferation of HL-60 cells by 28, 96, and 63%, respectively. The structure-activity relationship established from the results revealed that hydroxyl group at C-1 and prenyl group at C-2 had an important role.

Acridines↗
PubMed1999

HL-60 differentiating activity and flavonoid content of the readily extractable fraction prepared from citrus juices.

Citrus plants are rich sources of various bioactive flavonoids. To eliminate masking effects caused by hesperidin, naringin, and neoeriocitrin, the abundant flavonoid glycosides which make up 90% of the conventionally prepared sample, the readily extractable fraction from Citrus juice was prepared by adsorbing on HP-20 resin and eluting with EtOH and acetone from the resin and was subjected to HL-60 differentiation assay and quantitative analysis of major flavonoids. Screening of 34 Citrus juices indicated that King (C. nobilis) had a potent activity for inducing differentiation of HL-60, and the active principles were isolated and identified as four polymethoxylated flavonoids, namely, nobiletin, 3,3',4',5,6,7, 8-heptamethoxyflavone, natsudaidain, and tangeretin. HPLC analysis of the readily extractable fraction also indicated that King contained high amounts of these polymethoxylated flavonoids among the Citrus juices examined. Principal component and cluster analyses of the readily extractable flavonoids indicated peculiarities of King and Bergamot.

Cell Differentiation↗
PubMed1999

Antiproliferative effects of the readily extractable fractions prepared from various citrus juices on several cancer cell lines.

To eliminate the masking effect by flavonoid glycosides, which comprise approximately 70% of conventionally prepared sample, the readily extractable fraction from Citrus juice, which was prepared by adsorbing on HP-20 resin and eluting with ethanol and acetone from the resin, was subjected to antiproliferative tests against several cancer cell lines. Screening of 34 Citrus juices indicated that King (Citrus nobilis) strongly inhibited proliferation of all cancer cell lines examined. Sweet lime and Kabuchi inhibited three of the four cancer cell lines. In contrast, these samples were substantially less cytotoxic toward normal human cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Quantitation of flavonoid constituents in citrus fruits.

Twenty-four flavonoids have been determined in 66 Citrus species and near-citrus relatives, grown in the same field and year, by means of reversed phase high-performance liquid chromatography analysis. Statistical methods have been applied to find relations among the species. The F ratios of 21 flavonoids obtained by applying ANOVA analysis are significant, indicating that a classification of the species using these variables is reasonable to pursue. Principal component analysis revealed that the distributions of Citrus species belonging to different classes were largely in accordance with Tanaka's classification system.

Analysis of Variance↗
PubMed1999

Isolation of furocoumarins from bergamot fruits as HL-60 differentiation-inducing compounds.

The HL-60 differentiation-inducing compounds in bergamot fruits were isolated with column chromatography and identified as bergamottin, bergapten, and citropten by (1)H and (13)C NMR. Their HL-60 differentiation-inducing activity was measured by examining nitro blue tetrazolium (NBT) reducing, nonspecific acid esterase (NSE), specific esterase (SE), and phagocytic activities, and bergamottin showed the strongest activity among the coumarins isolated from bergamot fruits. The structure-activity relationship obtained from HL-60 differentiation assay suggests that hydrophobicity of furocoumarins is correlated with their activity.

Antineoplastic Agents↗
PubMed1999

The antiproliferative effect of acridone alkaloids on several cancer cell lines.

Fifteen acridone alkaloids were examined for their antiproliferative activity toward monolayers and suspension of several types of cancer and normal human cell lines. As a result, atalaphyllidine (9), 5-hydroxy-N-methylseverifoline (11), atalaphyllinine (12), and des-N-methylnoracronycine (13) showed potent antiproliferative activity against tumor cell lines, whereas they have weak cytotoxicity on normal human cell lines. The structure-activity relationship established from the results revealed that a secondary amine, hydroxyl groups at C-1 and C-5, and a prenyl group at C-2 played an important role for antiproliferative activities of the tetracyclic acridones.

Acridines↗