Olanzapine-induced delirium in a terminally ill cancer patient.
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Antiemetics↗
Biomedical subjects
Satoshi Inoue
Publications and source records attributed to Satoshi Inoue.
Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer.
Although estrogen is known to play a crucial role in the pathogenesis of breast cancer, the molecular mechanisms underlying the action of estrogen remain elusive. In the present study, we focused on keratinocyte growth factor (KGF) and its receptor (KGFR) in the pathogenesis of breast cancer, as a growth factor mediating estrogen action, since significant roles of KGF were demonstrated in various steroid hormone-dependent tissues. First, using paraffin-embedded specimens from 42 breast cancer patients, we examined expression patterns of KGF and KGFR by both immunohistochemistry using newly generated antibodies and nonradioactive in situ hybridization with T-T dimerized synthetic oligonucleotide probes. We next compared the results with the expression of estrogen receptor (ER) alpha and beta, proliferative activity and apoptotic frequency (TUNEL staining). Also, the similar approaches were taken to analyze the expression and role of KGF in ER-positive (MCF7, ZR-75-1) and ER-negative (SK-BR-3, MDA-MB-231) human breast cancer cell lines in vitro. In the surgical specimens, KGF was expressed in cancer cells as well as stromal cells in 19/42 cases (45%), while KGFR was found in cancer cells in 24/42 cases (57%). The distribution of protein and mRNA in the analysis of both KGF and KGFR expression generally coincided. Moreover, KGF expression was closely associated with the expression of ER alpha, and the coexpression of KGF and KGFR significantly correlated with lower TUNEL index, but not with proliferative activity. In accordance with the in vivo findings, KGF expression was detected only in ER alpha-positive MCF7 and ZR-75-1 cells in vitro. And more importantly, we found the inhibitory effect of KGF upon the induction of apoptosis by anticancer drugs in MCF7 cells. Collectively, our results indicate that ER alpha may be involved in KGF expression, and that KGF may play antiapoptotic roles, rather than mitogenic, in human breast cancer.
Adenocarcinoma↗
Assembly of the silk fibroin elementary unit in endoplasmic reticulum and a role of L-chain for protection of alpha1,2-mannose residues in N-linked oligosaccharide chains of fibrohexamerin/P25.
Silk fibroin of Bombyx mori is secreted from the posterior silk gland (PSG) as a 2.3-MDa elementary unit, consisting of six sets of a disulfide-linked heavy chain (H-chain)-light chain (L-chain) heterodimer and one molecule of fibrohexamerin (fhx)/P25. Fhx/P25, a glycoprotein, associates noncovalently with the H-L heterodimers. The elementary unit was found and purified from the endoplasmic reticulum (ER) extract of PSG cells. A substantial amount of fhx/P25 unassembled into the elementary unit was also present in ER. In normal-level fibroin-producing breeds (J-139 and C108), the elementary unit contained fhx/P25 of either 30 kDa (major) or 27 kDa (minor). The 27-kDa fhx/P25 was produced from the 30-kDa form by digestion with the bacterial alpha1,2-mannosidase in vitro. The elementary unit in the ER extract contained only the 30-kDa fhx/P25, whereas both 30- and 27-kDa forms of fhx/P25 were present in the ER plus Golgi mixed extracts. In naked-pupa mutants [Nd(2), Nd-s and Nd-sD], extremely small amounts of fibroin were produced and they consisted of one molecule of 27-kDa fhx/P25 and six molecules of H-chain but no L-chain. When the Nd-sD mutant was subjected to transgenesis with the normal L-chain gene, the (H-L)6fhx1-type elementary unit containing the 30-kDa fhx/P25, was produced. These results suggest that fhx/P25 in the elementary unit is largely protected from digestion with Golgi alpha1,2-mannosidases when L-chains are present in the unit. Models suggesting a role of L-chain for the protection of alpha1,2-mannose residues of fhx/P25 are presented.
Animals↗
Neuroleptic malignant syndrome after haloperidol and fentanyl infusion in a patient with cancer with severe mineral imbalance.
This case report describes a terminally ill patient with cancer with severe hypophosphataemia, hypocalcemia, and hypomagnesemia who developed neuroleptic malignant syndrome after administration of a combination of haloperidol and fentanyl. The chief etiology of neuroleptic malignant syndrome in this patient was administration of haloperidol, but fentanyl and coexisting mineral imbalance could have contributed to development of the syndrome. Palliative care clinicians should be aware that neuroleptic malignant syndrome can occur in their patients receiving haloperidol.
Aged↗
Four-year water degradation of a resin-modified glass-ionomer adhesive bonded to dentin.
Glass-ionomers are auto-adhesive to tooth tissue through combined micro-mechanical and chemical bonding. How much each of the two bonding components contributes to the actual bonding effectiveness is, however, not known and there is not much information available on long-term stability. The objective of this study was to assess the bonding effectiveness of a resin-modified glass-ionomer adhesive to dentin after 4 yr of water storage. Fuji Bond LC (GC) was applied without (i) and with pretreatment using (ii) a polyalkenoic acid conditioner and (iii) a 37.5% phosphoric acid etchant. The etchant was used to exclude any chemical interaction with hydroxyapatite. The micro-tensile bond strength ( microTBS) to dentin decreased significantly over the 4 yr period in all three experimental groups. After 24 h and 4 yr, the lowest micro TBS was recorded when dentin was not pretreated. The highest micro TBS was obtained following polyalkenoic acid pretreatment, although this was not significantly different from specimens that were pretreated using phosphoric acid. Pretreating dentin with phosphoric acid intensified micromechanical interlocking at the expense of chemical bonding potential to hydroxyapatite. Nevertheless, correlating the micro TBS data with failure analysis through scanning electron microscopy and transmission electron microscopy indicated that combined micro-mechanical and chemical bonding involving pretreatment with the polyalkenoic acid conditioner yielded the most durable bond.
Acid Etching, Dental↗
Systemic and mucosal immunity in rhesus macaques immunized with HIV-1 peptide and gp120 conjugated to Brucella abortus.
HIV vaccine testing in primates is an important method for determining the possibility of vaccine benefit in humans. Goals of HIV-1 vaccination include establishing neutralizing antibodies and a strong CD8(+) T-cell response. We tested a novel vaccine conjugate for its ability to elicit relevant immune responses to HIV proteins and peptides in rhesus macaques. A neutralizing epitope, V3 loop peptide from HIV-1 envelope, was coupled to heat-inactivated Brucella abortus (V3-HKBA). Rhesus macaques were immunized with this conjugate in the anterior thigh. After two immunizations V3-specific antibodies were found in the sera and at mucosal sites. Neutralizing activity of these antibodies was demonstrated by syncytia inhibition assays. Cellular immune recall responses were demonstrated by antigen-specific induction of interferon-gamma and Regulation on Activation Noraml T Cell Expressed and Secreted (RANTES) secretion in vitro. These results confirm and extend preliminary studies in mice that suggest HKBA is an effective carrier that promotes neutralizing antibody secretion at relevant mucosal sites, as well as cellular immune responses that are correlated with viral protection.
AIDS Vaccines↗
Rabies virus stimulates nitric oxide production and CXC chemokine ligand 10 expression in macrophages through activation of extracellular signal-regulated kinases 1 and 2.
Macrophages represent an essential part of innate immunity, and the viral infection of macrophages results in the release of multiple proinflammatory mediators, such as nitric oxide (NO), cytokines, and chemokines. This study was undertaken to define the molecular mechanism of macrophage activation in response to rabies virus (RV) infection. In RAW264 murine macrophage cells, a well-characterized macrophage model, RV replication was strictly restricted, whereas cell proliferation was significantly enhanced upon RV inoculation. Transcriptional analyses for the expression of inducible forms of NO synthase (iNOS), cytokines, and chemokines revealed that RV virions potentiate the gene expression of iNOS and CXC chemokine ligand 10 (CXCL10), a major chemoattractant of T helper cell type 1. However, RV stimulation had little or no effect on the expression profiles of proinflammatory cytokines and other types of chemokines. In macrophages stimulated with UV-inactivated RV virions, as well as infectious viruses, the phosphorylation of extracellular signal-regulated kinase (ERK) 1 and 2, members of the mitogen-activated protein kinase family, was significantly induced. Specific inhibitors of MAPK/ERK kinase reduced the RV-induced production of NO and CXCL10. Furthermore, the RV-induced activation of the ERK1/2 pathway was severely impaired by the neutralization of the endosomal and lysosomal pH environment with lysosomotropic agents, indicating that endocytosis is a key step leading to the activation of ERK1/2 signaling. Taken together, these results suggest that the ERK1/2-mediated signaling pathway plays a cardinal role in the selective activation of macrophages in response to RV virions, thereby regulating cellular functions during virus infection.
Animals↗
Estrogen receptors and their downstream targets in cancer.
Estrogen has crucial roles in the proliferation of cancer cells in reproductive organs such as the breast and uterus. Estrogen-stimulated growth requires two estrogen receptors (ERalpha and ERbeta) which are ligand-dependent transcription factors. High expression of ERs is observed in a large population of breast tumors. In addition, the positive expression of ERs correlates with well-differentiated tumors, a favorable prognosis, and responsiveness to an endocrine therapy with anti-estrogen drugs in patients with breast cancer. Transcription activities of ERs can be regulated by interacting proteins such as coactivators and kinases as well as ligand-binding. Moreover, ER isoforms lacking an ability to transactivate are involved in breast cancer. Downstream target genes of ERs have important roles in mediating the estrogen action in breast cancer. We have isolated and characterized several novel estrogen-responsive genes to clarify the molecular mechanism of the estrogen action in target cells. Among these genes, the estrogen-responsive finger protein (Efp) was found to be highly expressed in breast cancer. Efp as a ubiquitin ligase (E3) is involved in the proteasome-dependent degradation of the 14-3-3sigma protein, one of cell cycle brakes, this degradation resulting in the promotion of breast cancer growth. A full understanding of the expression and function of ERs and their target genes could shed light on how estrogen stimulates the initiation and promotion of cancer, providing a new approach to diagnose and treat cancer.
14-3-3 Proteins↗
Molecular mechanism of estrogen action and its role in bone metabolism and brain functions.
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DNA-Binding Proteins↗
Preparation of a positive control DNA for molecular diagnosis of Bacillus anthracis.
Bacillus anthracis is considered to be one of the most potent biological weapons because of its highly pathogenic nature and efficiency of transmission. Routinely, a presumptive diagnosis of anthrax is achieved if the bands with predicted sizes are detected after the PCR targeted to the pag and cap genes residing on pXO1 and pXO2 plasmids, respectively. A positive control DNA prepared from the standard strains of B. anthracis (PAI and PAII) is usually included in the PCR tests. The handling of living B. anthracis, however, requires physical containment. The inclusion of DNA from B. anthracis as a positive control in the PCR test also has a potential risk of cross contamination that may confuse the results. In order to circumvent such problems, we attempted to construct a recombinant plasmid harboring the fragments of the pag and cap genes that could be distinguished from authentic sequences by the presence the restriction-enzyme site, the EcoRV site for the pag gene and the BamHI site for the cap gene, respectively, which were newly introduced. The strategy reported here provides a safe and reproducible positive-control DNA template. It also allows the detection of possible cross contamination, indicating that this strategy would be useful and convenient for the molecular identification of not only B. anthracis but also other highly pathogenic microbes.
Animals↗
The absence of anti-rabies antibody in the sera of feral raccoons (Procyon lotor) captured in Hokkaido, Japan.
Feral raccoons captured in Hokkaido, Japan were examined for the presence of rabies virus neutralizing antibody (VNA). Between 2000 to 2002, 741 serum samples were collected and then subjected to VNA titer determination by rapid fluorescent focus inhibition test (RFFIT). Sera showing RFFIT titers of > or =1:25 have been considered as positive according to previous reports. VNA was detected in none of serum samples from the feral raccoons. The present study provides valuable background information for rabies prevention in Japan. The potential risk of raccoon-derived rabies in the wilderness has been of concern because of the increasing number of feral raccoons originally introduced from rabies-endemic countries. The continuous monitoring of sick and/or dead wild raccoons would help to prevent an epidemic spread of raccoon rabies.
Age Factors↗
Effect of bur-cut dentin on bond strength using two all-in-one and one two-step adhesive systems.
PURPOSE: To compare the microtensile bond strength (MTBS) of two all-in-one adhesive systems and one experimental two-step self-etching adhesive system to two types of bur-cut dentin. MATERIALS AND METHODS: Using one of the three adhesives, Xeno CF Bond (Xeno), Prompt L-Pop (PL), or the experimental two-step system ABF (ABF), resin composite was bonded to flat buccal and root dentin surfaces of eight extracted human premolars. These surfaces were produced using either regular-grit or superfine-grit diamond burs. After storage overnight in 37 degrees C water, the bonded specimens were sectioned into six or seven slices approximately 0.7 mm thick perpendicular to the bonded surface. They were then subjected to microtensile testing. The surfaces of the fractured specimens were observed microscopically to determine the failure mode. In addition, to observe the effect of conditioning, the two types of bur-cut dentin surfaces were conditioned with the adhesives, rinsed with acetone, and observed with SEM. RESULTS: When Xeno and PL were bonded to dentin cut with a regular-grit diamond bur, MTBS values were lower than to superfine bur-cut dentin, and failures occurred adhesively at the interface, whereas the experimental two-step adhesive showed no significant difference in microtensile bond strength between two differently cut surfaces. CONCLUSION: The all-in-one adhesives tested here improved bond strengths when bonded to superfine bur-cut dentin as a substrate, whereas the experimental two-step adhesive system showed unchanged bonding to both regular and superfine bur-cut dentin surfaces.
Acetone↗
[Hormone replacement therapy].
Hormone Replacement Therapy (HRT) is replacement of depleted endogenous estrogen for postmenopausal women. Usually progestin is used in combination to avoid endometrial proliferation. As for bone metabolism, estrogens exert bone protective effect through inhibition of bone absorption. HRT has been shown to improve bone mineral density and to lower the risk of osteoporotic bone fracture. However, the results of recent large scale clinical studies in the U.S. indicate that HRT not only raise the risk of breast cancer, but also increase the incidence of atherosclerotic cardiovascular diseases. According to these studies, the benefit of HRT does not outweigh its risk except the treatment of postmenopausal vasomotor symptoms. To resolve this problem, low dose HRT and SERM (selective estrogen receptor modulator) regimens are under investigation.
Adolescent↗
[Selective estrogen receptor modulators: mechanisms of action and their tissue selectivity].
The SERMs (Selective Estrogen Receptor Modulators) exert selective agonistic or antagonistic effects on various estrogen target tissues. Conformational change of SERM-bound Estrogen Receptor (ER) and tissue specific expression patterns of transcription co-factors have been well investigated as the underlying factors of tissue selectivity of the SERMs. Nongenomic action, modulation of protein levels of ER and co-factors, and activation of other nuclear receptors, have been also reported as mechanisms of tissue selectivity by SERMs.
Animals↗
[Signaling networks by steroid hormones].
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Drug Design↗
[Molecular mechanism involved in estrogen action and its role in bone metabolism and brain function].
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Animals↗
EBAG9/RCAS1 expression and its prognostic significance in prostatic cancer.
Estrogen receptor-binding fragment-associated gene 9 (EBAG9) has been identified as a primary estrogen-responsive gene from MCF-7 human breast cancer cells (Watanabe T, et al., Mol Cell Biol 1998;18:442-9). EBAG9 is identical with RCAS1 (receptor-binding cancer antigen expressed on SiSo cells), which has been reported as a cancer cell surface antigen implicated in immune escape (Nakashima M, et al., Nat Med 1999;5:938-42). In our present study, we examined EBAG9 expression in human prostatic tissues and investigated its prognostic significance in patients with prostatic cancer. EBAG9 expression in normal prostatic epithelial cells and PC-3, DU145 and LNCaP cancer cells was determined by Western blot analysis. Immunohistochemic analysis was performed in 21 benign and 81 malignant prostatic specimens, and patients' charts were reviewed for clinical, pathologic and survival data. EBAG9 was abundantly expressed in the prostate cancer cells compared to the normal epithelial cells. Strong and diffuse immunostaining in the cytoplasm of EBAG9 was found in 44 of 81 (54%) cancerous tissue samples. EBAG9 expression significantly correlated with advanced pathologic stages and high Gleason score (p = 0.0305 and < 0.0001, respectively). EBAG9 was more frequently expressed at sites of capsular penetration (79%) and lymph node metastasis (100%) compared to intracapsular primary tumors (54%) (p = 0.0264 and 0.0048, respectively). Positive EBAG9 immunoreactivity significantly correlated with poor PSA failure-free survival (p = 0.0059). EBAG9/RCAS1 may play a significant role in cancer progression via an immune escape system. Immunodetection of EBAG9/RCAS1 expression can be a negative prognostic indicator for patients with prostatic cancer.
Aged↗
Estrogen receptor beta mediates the inhibitory effect of estradiol on vascular smooth muscle cell proliferation.
OBJECTIVES: It has been demonstrated that 17beta-estradiol (E2) has an inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs) through an estrogen receptor (ER)-dependent pathway. Both ER subtypes, classical ER (ERalpha) and the newly identified ER subtype (ERbeta), are expressed in VSMCs. However, it remains unknown which receptor plays the critical role in the inhibitory effect on VSMC proliferation. METHODS AND RESULTS: We constructed replication-deficient adenoviruses bearing the coding region of human ERalpha, ERbeta, and the dominant-negative form of ERbeta (designated AxCAERalpha, AxCAERbeta, and AxCADNERbeta, respectively). Prior to infection with the adenoviruses, 100 nmol/l E2 attenuated DNA synthesis by up to 14% and transactivated the estrogen-induced expression of the desired mRNA in rat VSMCs. This was accompanied by increased transcriptional activity of estrogen responsive element in response to E2, and the increase was comparable between AxCAERalpha and AxCAERbeta. When VSMCs were infected with AxCAERbeta at a multiplicity of infection of 5 or higher, DNA synthesis as well as cell number decreased by 50% in response to E2, and the effect was abolished by co-infection with AxCADNERbeta. In contrast, when VSMCs were infected with AxCAERalpha, the reduction in DNA synthesis was minimal. CONCLUSIONS: Our results indicate that ERbeta is more potent than ERalpha in the inhibitory effect on VSMC proliferation.
Adenoviridae↗