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Biomedical subjects

Y Endo

Publications and source records attributed to Y Endo.

At least 199 records · Page 11Linked to original sources
PubMed1999

Isolation of deoxycytidine kinase from Ehrlich carcinoma cells by affinity chromatography based on a substrate analog, 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosyl-N4-palmitoylcytosine++ +.

Deoxycytidine kinase from Ehrlich carcinoma cells was purified 10400-fold by ammonium sulfate fractionation and affinity chromatography using Sepharose 4B coupled to 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosyl-N4-palmitoylcytosine , with a yield of 45%. The purified enzyme preparation showed a single major band with a molecular weight of 32000 on SDS-PAGE. The enzyme phosphorylated deoxyadenosine, deoxyguanosine, cytidine, and several deoxycytidine analogues as well as deoxycytidine. Also, the kinetic parameters of the enzyme for the substrates were estimated.

Animals↗
PubMed1999

Dicarba-closo-dodecaboranes as a pharmacophore. Retinoidal antagonists and potential agonists.

Synthesis and biological evaluation of the first dicarba-closo-dodecaborane (carborane) derivatives of retinoids are described. Their retinoidal activity were examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells. High retinoidal activity (agonist or antagonist for retinoic acid receptor (RAR) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule. The 4-carboranyl-substituted compounds (7, 11) showed antagonistic activity but no agonistic activity even in the presence of the potent synergist HX630. On the other hand, the 3-carboranyl-substituted compounds (8, 12) showed potential agonistic activity, but no antagonistic activity. The results indicates that carboranes are applicable as the hydrophobic moiety of biologically active molecules.

Boron Compounds↗
PubMed1999

Dicarba-closo-dodecaboranes as a pharmacophore. Novel potent retinoidal agonists.

The synthesis and biological evaluation of the dicarba-closo-dodecaborane (carborane) derivatives of retinoids are described. Retinoidal activity was examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells. High retinoidal activity (agonist or antagonist for the retinoid receptor RAR) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule. 4-[4-(1,2-Dicarba-closo-dodecaboran-1-yl)phenylamino]b enzoic acids and 4-[3-(1,2-dicarba-closo-dodecaboran-1-yl)phenylamino]b enzoic acids showed potent agonistic activity at concentrations of 10(-8)-10(-9) M. The results indicate that carboranes are applicable as the hydrophobic moiety of biologically active molecules.

Boron Compounds↗
PubMed1999

Fatty acid synthase expression in Japanese breast carcinoma patients.

Fatty acid synthase (FAS) is the key enzyme required for the conversion of dietary carbohydrates to fatty acids. Recent studies have demonstrated that high levels of FAS expression occur in a variety of cancers, including breast cancer. We evaluated 243 primary breast cancer patients in the period between 1989 and 1996. Immunohistochemical staining for FAS was performed on formaline-fixed, paraffin-embedded sections. FAS staining intensity was graded as low or high. The expression of FAS was high in 145 (60%) and low in 98 cases (40%). A weak correlation between FAS expression and nodal status was noted in premenopausal patients (p=0. 01). FAS was associated with estrogen receptor (p=0.0022) and progesterone receptor (p=0.0085) status. We found that a low expression of FAS was significantly related to a shorter disease-free survival (DFS) rate in estrogen receptor positive patients (p=0.024) and a similar trend was recognized in progesterone receptor positive patients (p=0.083). The low FAS group showed better DFS and OS in all but ER-/PgR- cases (p=0.011, 0.076). This study showed close correlations between immunohistochemical FAS expression and steroid hormone receptors in premenopausal patients. The use of FAS expression may increase the diagnostic utility of ER and PgR in premenopausal patients. FAS may be able to predict the responsiveness of tumors to endocrine therapy.

Adult↗
PubMed1999

Determinants in chemosensitivity of oncogene-transformed NIH3T3 cells to 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine.

2'-C-Cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine (CNDAC) is a novel 2'-deoxycytidine (dCyd) analogue with potent antitumor activity. To elucidate the determinants of chemosensitivity to CNDAC, the intracellular accumulation of CNDAC and the activities of dCyd kinase and cytidine deaminase were investigated in transformed NIH 3T3 cells with different genetic bases. The results indicate that the primary determinants of chemosensitivity to CNDAC are different in each cell type, but membrane transportation and the enzyme activities of dCyd kinase and cytidine deaminase are critical factors underlying the antitumor action of CNDAC. Moreover, the expression or function of these factors appears to be influenced by the activation of various oncogenes.

3T3 Cells↗
PubMed1999

A human seminoma xenograft model with regional lymph node metastasis.

PURPOSE: To establish a seminoma orthotopic model with lymph node metastasis to investigate the factors related to the lymphophilic behavior of seminoma cells. MATERIALS AND METHODS: Testicular seminoma xenografts were established by the inoculation of small fragments from subcutaneous (s.c.) xenografts that had previously been established in severe combined immunodeficient (SCID) mice with a supraclavicular lymph node metastasis from a human seminoma. Hematologic dissemination of tumor cells was analyzed by polymerase chain reaction (PCR) amplification of the human beta-globin gene. Xenograft messenger RNA levels of metastasis-related genes were examined by reverse transcription (RT)-PCR. RESULTS: Testicular seminoma xenografts grew in 32/32 (100%) of the inoculated mice, of which 15 mice (47%) developed macroscopic metastasis to the renal hilar lymph node. Circulating tumor cells and tumor cell shedding in the lung and liver were detectable by PCR assay in 25/32 (78%), 32/32 (100%), and 27/32 (84%) mice, respectively, although metastatic foci were not histologically evident in these organs. Increased expression of matrix metalloproteinase-2 (MMP-2), membrane-type 3 matrix metalloproteinase (MT3-MMP) and vascular endothelial growth factor (VEGF), and reduction in expression of plasminogen activator inhibitor-2 (PAI-2) were demonstrated by RT-PCR assay in the testicular xenografts as compared with the s.c. xenografts. CONCLUSIONS: This model mimics the lymphophilic behavior of seminoma and may help in elucidating the molecular mechanism of tumor spread via the lymphatics.

Animals↗
PubMed1999

[An autopsy case of Goodpasture's syndrome with P-ANCA and systemic vasculitis].

A 72-year-old woman was admitted because of anorexia and dyspnea. She was given a diagnosis of pulmonary hemorrhage and renal failure. Despite treatment with high-dose steroid and hemodialysis, the patient died of disseminated intravascular coagulation on the 9th hospital day. Autopsy revealed intra-alveolar hemorrhage, crescentic glomerulonephritis, and systemic vasculitis with fibrinoid necrosis. A direct immunofluorescence study demonstrated linear deposition of IgG along the glomerular basement membrane (GBM). Both anti-GBM antibody and anti-neutrophil cytoplasmic antibody with perinuclear pattern (P-ANCA) were detected in the patient's serum by enzyme immunoassay. Goodpasture's syndrome with P-ANCA was diagnosed. There has been some controversy as to whether vasculitis occurs in patients with Goodpasture's syndrome. This was a rare example of well-documented Goodpasture's syndrome with P-ANCA and systemic vasculitis, the exact etiologic relationships among which remain to be clarified.

Aged↗
PubMed1999

[Assay and detection methods for urokinase-type plasminogen activator and its related-factors].

The urokinase-type plasminogen activator (u-PA) has been implicated in invasion and metastasis of various cancers including lung, breast, gastric and colon cancers. The u-PA system consists of plasmin, u-PA, specific u-PA receptor and the serpins, PAI-1 and PAI-2. It has been demonstrated that the reciprocal actions among the components of the u-PA system are much important for regulating u-PA activity. Recent studies are focusing on the interaction between the u-PA system and cell adhesion molecules such as integrins, and the physiological significance in vivo of u-PA system-related proteins. We introduce here the useful methods to examine the u-PA enzyme activity and the expression of proteins and genes related with the u-PA system for clinical cancer specimens.

Antibodies, Monoclonal↗
PubMed1999

Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer.

Neogenesis of lymphatic vessel and lymphatic invasion is frequently found in the stroma of cancers, but the mechanisms of this phenomenon remain unclear. Vascular endothelial growth factor C (VEGF-C) is known to be the only growth factor for the lymphatic vascular system, and its receptor has been identified as Flt4. To clarify the mechanism of lymphatic invasion in cancer, we studied the expression of VEGF-C and flt4 genes in gastric cancer tissues. VEGF-C mRNA was mainly expressed in primary tumors (15 of 32; 47%), but the frequency of VEGF-C mRNA expression was low in normal mucosa (4 of 32; 13%). In primary tumors, there was a significant relationship between VEGF-C and flt4 mRNA expression. In contrast, Flt4 was mainly expressed on the lymphatic endothelial cells but not in cancer cells. A strong correlation was found between VEGF-C expression and lymph node status, lymphatic invasion, venous invasion, and tumor infiltrating patterns. Cancer cells in the lymphatic vessels frequently showed intracytoplasmic VEGF-C immunoreactivity. Furthermore, there was a close correlation between VEGF-C tissue status and the grade of lymph node metastasis. Patients with high expression of VEGF-C protein had a significantly poorer prognosis than did those in low VEGF-C expression group. By the Cox regression model, depth of wall invasion, lymph node metastasis, and VEGF-C tissue status emerged as independent prognostic parameters, and the VEGF-C tissue status was ranked third as an independent risk factor for death. These results strongly suggest that cancer cells producing VEGF-C may induce the proliferation and dilation of lymphatic vessels, resulting in the development of invasion of cancer cells into the lymphatic vessel and lymph node metastasis.

Biomarkers, Tumor↗
PubMed1999

Changes in beta-endorphin and stress-induced analgesia in mice after exposure to forced walking stress.

In this study, we attempted to clarify the correlation between changes in the level of beta-endorphin (beta-EP) in the mouse brain and the stress-induced analgesia (SIA) after exposing animals to forced walking stress. The immunohistochemical distribution of beta-EP after stress was first analyzed quantitatively in mice and then more specifically using a microphotometry system with results showing that the fluorescence intensity of beta-EP in the peri-aqueductal gray matter (PAG) and arcuate nucleus of the medial basal hypothalamus (ARC) was increased 6 h after exposure to forced walking stress. Further, SIA was examined after exposing animals to the forced walking stress and the formalin test. At 6 h after forced walking stress, significant SIA was observed in the second phase (from 10 to 30 min after formalin injection) of the formalin-induced paw licking behavior, but not in the first phase (from 0 to 10 min after formalin injection). This SIA was antagonized by beta-EP-(1-27), an opioid epsilon receptor antagonist. In nonstressed mice, the injection of beta-EP produced a reduction in formalin-induced paw-licking in the second phase. A significant antinociceptive effect by beta-EP was well antagonized by beta-EP-(1-27). Thus, the present results suggest that the increase in beta-EP levels in PAG and/or ARC may be involved in SIA after exposure of mice to the forced walking stress.

Analgesia↗
PubMed1999

[Effect of adenosine on isolated afferent arterioles].

We investigated the direct effect of adenosine on afferent arterioles (Af-Arts) and the receptor subtype that mediates the constrictor or dilator action of adenosine. Af-Arts were isolated from the superficial cortex of rabbit kidney and perfused in vitro. Adenosine added to either the lumen or bath constricted the Af-Arts in a dose-dependent manner. This constriction was blocked by the A1 receptor antagonist, 6-oxo-3-(2-phenylpyrazole(1,5-a)pyridin-3-yl)-1 (6H)-pyridazinebutyric acid (FK838) or 8-cyclopentyl-1, 3-dipropylxanthine(DPCPX). We also examined the effect of adenosine on preconstricted Af-Arts with norepinephrine. Adenosine added to either the lumen or bath further constricted the preconstricted Af-Arts. In the presence of FK838, adenosine added to either the lumen or bath dilated the preconstricted Af-Arts, but in a different dose-dependent manner. Adenosine-induced dilation was inhibited by the A2 receptor antagonist, 3, 7-dimetyl-1-propargylxanthine(DMPX). These data indicate that adenosine constricts Af-Arts via A1 receptors and that adenosine dilates preconstricted Af-Arts via A2 receptors when A1 receptors are blocked.

Adenosine↗
PubMed1999

Dominant role of E-cadherin in the progression of bladder cancer.

PURPOSE: To elucidate factors with a role in the progression of bladder cancer. MATERIALS AND METHODS: One invasive (T24) and two superficial (RT4 and KK47) human bladder cancer cell lines, which express metastasis-related genes, were used. Cells were intravenously inoculated into chick embryos to evaluate metastatic potential to the liver. An orthotopic model with severe combined immunodeficiency mice was also used to investigate both histological appearance and changes in metastasis-related gene expression. Finally, gene expression patterns in a clinical setting were compared between superficial and invasive bladder cancers. RESULTS: In culture condition metastasis-related genes, including matrix metalloproteinases, urokinase-type plasminogen activator, and integrins alpha2 and alpha3 were continually expressed in T24 but only slightly or not at all in RT4 and KK47, respectively. The expression pattern of the metastasis-related genes in vitro reflected the characteristics of the original tumors. Liver metastasis in chick embryos was demonstrated not only with T24 cells, but also with RT4 cells in which enhanced expression of metastasis-related genes was induced. In the orthotopic model, histological appearances were in accordance with the characteristics of the original tumors, although enhanced gene expression was notable with RT4. Expression of E-cadherin by Western blotting was demonstrated only with RT4 under these experimental conditions. Furthermore, predominant E-cadherin mRNA expression was found in superficial and not in invasive human primary bladder cancers; expression of other genes was similar in the two groups. Dominant expression of E-cadherin in superficial tumors was confirmed by immunohistochemical analysis. CONCLUSIONS: These results implicate loss of E-cadherin expression as a critical factor in facilitating the progression of bladder cancer.

Animals↗
PubMed1999

Adsorption effects of activated charcoal on metaldehyde toxicity in rats.

Metaldehyde has been widely used as a main ingredient of solid fuel for making fire and slug baits in Japan. It is also marketed as a color flame tablet for party goods (ENGELFIRE). Consequently, children have been poisoned by eating such tablets which they mistook for candy. As a result, poison information center calls are increasing. According to POISINDEX, the treatment for metaldehyde poisoning consists in prevention of adsorption by activated charcoal, seizure control and airway protection. However, the optimum dose of charcoal is not established. We studied the quantitative adsorption capacity of activated charcoal for acute oral toxicity of metaldehyde in rats. In vivo toxicity and absorption tests for metaldehyde in Wister rats were done. The detoxifying effect of activated charcoal on metaldehyde toxicity and inhibition of metaldehyde absorption were investigated. Ratios used of po activated charcoal given 30 min after dosing to 400 mg metaldehyde/kg po were 5:1, 2:1, 1:1, 0.5:1. Serum metaldehyde was determined by gas chromatography in the control group (no charcoal) and the various experimental groups. Metaldehyde mortality was completely prevented at the ratio of 5:1. Gastrointestinal absorption of metaldehyde was reduced significantly by 45.3% in comparison to the control rats. There was no acetaldehyde detected in the serum of the metaldehyde-dosed rats. Metaldehyde poisoning may be prevented by early po administration of activated charcoal in a ratio of > 5:1 compared to metaldehyde. The theory that acetaldehyde is the primary toxic agent in metaldehyde poisoning should be re-evaluated.

Acetaldehyde↗
PubMed1998

Two lineages of mannose-binding lectin-associated serine protease (MASP) in vertebrates.

Mannose-binding lectin-associated serine protease (MASP) is a newly identified member of the serine protease superfamily. MASP is involved in host defense against pathogens through a novel system of complement activation, designated the lectin pathway. To elucidate the origin of the lectin pathway and the molecular evolution of MASP, we cloned six MASP cDNAs from five vertebrate species going from mammal to cyclostome. An alignment of the amino acid sequences deduced from the cDNAs revealed the presence of two different lineages of the MASP gene. This classification was supported by the precise correlation with two types of exon organization for the protease domain. One of the two lineages is unique in that a single exon encodes the protease domain, unlike most other serine proteases. All members of this group, termed the AGY type, have an AGY codon at the active site serine. A phylogenetic tree suggests that the AGY type diverged from another lineage, termed the TCN type, before the emergence of primitive vertebrates. Furthermore, the presence of MASP or MASP-like sequences in most vertebrate species suggests that the lectin pathway functions extensively in vertebrates and that its origin is traced back to the invertebrate stage.

Amino Acid Sequence↗
PubMed1998

Molecular cloning of feline CC-chemokine cDNAs.

cDNA clones of feline chemokines, MIP-1alpha, MIP-1beta and RANTES, were molecularly isolated with the purpose of using these sequences for future investigation of the inhibitory effects on lentivirus entry and their role in immunological functions. The feline MIP-1alpha and MIP-1beta cDNA clones spanned their entire coding regions encoding 93 and 92 amino acids, respectively. The amino acid sequences of feline MIP-1alpha and MIP-1beta compared to those of their human, mouse and rat counterparts showed similarities of 75.3-79.6% and 73.9-88.0%, respectively. Feline MIP-1alpha and MIP-1beta had four conserved cysteines with a structure made up of the first two cysteines that are characteristic of the CC-chemokine subfamily. The amino terminal of these MIP-1alpha and MIP-1beta sequences was distinctly hydrophobic, suggesting that they may function as signal peptides. A partial cDNA clone consisting of 193 bp was obtained for feline RANTES, and it also showed a high degree of sequence similarity to those of other species and contained the characteristic structure made up of adjacent cysteines. These molecular clones of feline chemokines will be useful in the examination of their inhibitory effect on the cellular entry of feline immunodeficiency virus.

Amino Acid Sequence↗
PubMed1998

Molecular cloning of feline Fas antigen and Fas ligand cDNAs.

The Fas antigen (FasA) and Fas ligand (FasL) are key molecules which mediate apoptosis. For investigation of apoptosis in cats, we isolated molecular clones of feline FasA and FasL cDNAs by using the polymerase chain reaction (PCR) method to amplify cDNAs from feline lymphoma cell lines. These feline FasA and FasL clones contained complete open reading frames encoding 314 and 280 amino acids, respectively. These feline FasA and FasL cDNA clones had structures characteristic of the tumor necrosis factor (TNF) receptor family and TNF family, respectively. The deduced amino acid sequence of feline FasA and feline FasL, respectively showed 45.0%-60.0% and 75.0%-90.0% similarity with their human, mouse and bovine counterparts. These data will be helpful for investigating the role of the FasA and FasL system in apoptosis and for studying the various diseases associated with the deregulation of apoptosis in cats.

Amino Acid Sequence↗
PubMed1998

Brain-derived neurotrophic factor induces rapid and transient release of glutamate through the non-exocytotic pathway from cortical neurons.

There is increasing interest in the involvement of neurotrophins in neural transmission and plasticity. Thus, we investigated the effects of brain-derived neurotrophic factor (BDNF) on glutamate release from cortical neurons. Treatment of cultured cortical neurons with BDNF induced rapid and transient release of glutamate. This effect was suggested to be mediated by TrkB activation because K252a inhibited the release of glutamate and BDNF phosphorylated TrkB within 30 s. BDNF-induced glutamate release was observed even when using Ca2+-free assay buffer but was inhibited by BAPTA-AM, a cell-permeable Ca2+ chelator. Therefore, BDNF-induced glutamate release was independent of extracelluar Ca2+ but dependent on intracellular Ca2+. Because normal neurotransmitter release is exocytotic, the involvement of the exocytotic pathway in BDNF-induced glutamate release was examined. As botulinum toxin is known to cleave exocytosis-associated proteins, thereby inhibiting exocytosis, it was applied to neurons prior to the release assay. Although botulinum toxin B cleaved VAMP2 and inhibited Ca2+-triggered glutamate release, it did not inhibit the BDNF-induced release of glutamate. These results strongly suggested that BDNF induces rapid and transient release of glutamate from cortical neurons through a non-exocytotic pathway.

Animals↗