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Biomedical subjects

Daisuke Inoue

Publications and source records attributed to Daisuke Inoue.

At least 37 records · Page 2Linked to original sources
PubMed2005

Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase.

Viruses depend on host-derived factors for their efficient genome replication. Here, we demonstrate that a cellular peptidyl-prolyl cis-trans isomerase (PPIase), cyclophilin B (CyPB), is critical for the efficient replication of the hepatitis C virus (HCV) genome. CyPB interacted with the HCV RNA polymerase NS5B to directly stimulate its RNA binding activity. Both the RNA interference (RNAi)-mediated reduction of endogenous CyPB expression and the induced loss of NS5B binding to CyPB decreased the levels of HCV replication. Thus, CyPB functions as a stimulatory regulator of NS5B in HCV replication machinery. This regulation mechanism for viral replication identifies CyPB as a target for antiviral therapeutic strategies.

Carcinoma, Hepatocellular↗
PubMed2005

Increased arterial carboxyhemoglobin concentrations in chronic obstructive pulmonary disease.

RATIONALE: Exhaled carbon monoxide (CO) and arterial blood carboxyhemoglobin concentrations (Hb-CO) increase in inflammatory pulmonary diseases. OBJECTIVES: To study whether arterial Hb-CO is useful to monitor disease activity in patients with chronic obstructive pulmonary disease (COPD) who had stopped smoking. METHODS: We measured arterial Hb-CO, arteriovenous Hb-CO differences, and FEV1 in 58 patients with COPD and 61 ex-smoking control subjects. RESULTS: Arterial Hb-CO concentrations in patients at stable conditions were higher than those in control subjects (p < 0.0001). Furthermore, the Hb-CO concentrations in patients at the exacerbations (p < 0.0001) were higher than those at the stable conditions. Arterial Hb-CO concentrations in patients at stage III were higher than those in patients at stage II, and the Hb-CO concentrations in patients at stage IV were higher than those in patients at stage III at the stable conditions and exacerbations. Arterial Hb-CO correlated with exhaled CO in patients with COPD at stage II and stage III at the exacerbations. Arterial Hb-CO inversely correlated with the arterial blood partial oxygen pressure and FEV1. Arteriovenous Hb-CO differences in patients at the exacerbations did not differ from those in patients at stable conditions and from those in control subjects. Moreover, arterial Hb-CO correlated with serum C-reactive protein values and serum lipid peroxide concentrations. CONCLUSIONS: These findings suggest that increased arterial Hb-CO may relate to severity in patients with COPD because of lung and systemic inflammation and production of reactive oxygen species.

Aged↗
PubMed2005

The proton pump inhibitor lansoprazole inhibits rhinovirus infection in cultured human tracheal epithelial cells.

To examine the effects of lansoprazole, a proton pump inhibitor, on rhinovirus infection in airways, human tracheal epithelial cells were infected with a major subgroup of rhinoviruses, type 14 rhinovirus. Rhinovirus increased the mRNA expression of intercellular adhesion molecule-1 (ICAM-1) in the cells, the major rhinovirus receptor, and the content of the soluble form of ICAM-1 (sICAM-1) and cytokines in supernatants. Lansoprazole reduced supernatant titers and RNA of rhinovirus, the susceptibility to rhinovirus infection, the ICAM-1 mRNA production, the number and fluorescence intensity of acidic endosomes in the cells, and supernatants sICAM-1 and cytokine concentrations including interleukin-1beta. Antibody to interleukin-1beta reduced baseline and rhinovirus-induced ICAM-1 production. These results suggest that lansoprazole inhibits rhinovirus infection by reducing ICAM-1 via partly endogenous production of interleukin-1beta, and by blocking the rhinovirus RNA entry into the endosomes. Lansoprazole may modulate airway inflammation by reducing the production of cytokines and ICAM-1 in rhinovirus infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Potential of predominant activated sludge bacteria as recipients in conjugative plasmid transfer.

We investigated the possibility of conjugative plasmid transfer to the predominant bacteria in activated sludge and the factors influencing the transfer frequency in the activated sludge process. We performed conjugative transfers of a self-transmissible, broad-host-range plasmid RP4 from Escherichia coli C600 to activated sludge bacteria by broth mating. Most of the activated sludge bacteria tested could acquire plasmid RP4, although the transfer frequencies varied from 8.8 x 10(-7) to 1.3 x 10(-2) transconjugants per recipient. The transfer frequencies in several strains were similar to, or higher than, that in intraspecific transfer to E. coli HB101. Matings under various environmental conditions showed that factors relevant to physiological activity, such as temperature and nutrient conditions, seemed to affect the transfer frequency. In addition, conjugative transfer was detected even in filtered raw and treated wastewaters. Thus, the predominant activated sludge bacteria seem to have sufficient potential as recipients in conjugative plasmid transfer under the conditions likely to occur in the activated sludge process. Transfer frequency was reduced by agitation in the presence of suspended solid. This may suggest that conjugative plasmid transfer is physically inhibited in aeration tanks.

Cell Culture Techniques↗
PubMed2005

[Genes involved in bone formation as a therapeutic target for osteoporosis].

Osteoblasts are derived from mesenchymal stem cells, common progenitors for adipocytes and other lineages. While transcription factors such as Runx2/Cbfa1 and Osterix are absolutely required for osteoblast differentiation, simply increasing their expression does not necessarily lead to increased bone formation. In contrast, genes such as deltafosB and an AP-1 target, interleukin-11, which have been shown to enhance bone formation in vivo and to be induced by mechanical stress and PTH, can be better therapeutic targets to develop drugs that stimulate bone formation.

Animals↗
PubMed2005

[Vitamin D and its derivatives as anti-osteoporotic drugs].

Vitamin D, particularly its active form, has been most widely used in Japan for the treatment of osteoporosis. However, clinical evidence for its efficacy as an anti-osteoporotic drug is scarce in terms of fracture prevention. Recent reports suggest that active vitamin D or its analogs may prevent fracture not only through enhancement of intestinal calcium absorption but also by improving bone quality and/or strength independently of bone mass and by improving neuromuscular function to reduce the number of falls.

Accidental Falls↗
PubMed2005

[Bone quality, strength, and turnover].

Skeletal integrity is maintained by remodeling, a sequential process of bone resorption and formation. Bone mass and quality depends on a dynamic equilibrium between resorption and formation during a remodeling process. Bone strength, or its ability to resist to fractures, is determined by both mass and quality of bone. Recent clinical studies indicate that activity of remodeling, i.e., bone turnover, is not only a predictor of future changes in bone mass but also a determinant of the future fracture risk independent of bone mass and that fracture prevention by anti-resorptives cannot be solely explained by increased bone mass but is more closely associated with improved bone quality, especially, suppression of bone turnover. This review will focus on the impact of bone turnover on bone quality and fracture risk and its clinical relevance.

Bone and Bones↗
PubMed2005

[Differential diagnosis of abnormalities in serum calcium levels].

Extracellular calcium levels are strictly regulated through actions of the two major calcium-regulating hormones, PTH and active vitamin D (1alpha,25-dihydroxyvitamin D), on their target organs including intestines, kidneys and bone. Accordingly, both hypercalcemia and hypocalcemia are mostly caused by either deregulated actions of these hormones or functional abnormalities in their target organs. This overview summarizes diseases causing serum calcium abnormalities and their differential diagnosis.

Calcium↗
PubMed2005

[Current status and problems in the chemotherapy of our outpatient clinic in the department of clinical oncology].

The department of clinical oncology performed an analysis of the current situation and problems inherent to 4500 chemotherapies of the outpatient clinic for the last 20 months using a new department of the outpatient clinical treatment. Divided into primary organs and the application of chemotherapy are as follow: breast cancer 49%, and gastrointestinal cancer 47% (esophageal cancer 4%, stomach cancer 28%, colorectal cancer 15%) and others 4%. In terms of time consumed by chemotherapy, there were differences in the tumors, regimens and ages. Within one hour, 40% of all chemotherapies mainly included those of breast cancers. From one to two hours, 40% included half breast cancers and half gastro-intestinal cancers, two to three hours, 15% the same as one to two hours. Over 3 hours, 5% mainly include those of gastro-intestinal cancers. In outpatient clinical chemotherapy, there were no human errors such as the use of wrong drugs and wrong intravenous injections. There were a few patients with adverse effects of chemotherapy including high fever with bone marrow suppression and severe diarrhea, who had an emergency admission to the hospital. As we perform an outpatient clinical chemotherapy with safe, it is important to coordinate with family doctors. To decrease the patients' effort of outpatient clinic, we request the treatment of high fever and the dose of G-CSF for bone marrow suppression to family doctors. The outpatient clinical chemotherapy enables to offer the suitable tailor-made treatment for each individual and to control the adverse effects of any regimen. But, patients' waiting period is still longer due to lack of numbers of doctors. To improve these statuses, careful consideration will be required for the trusting relationship with paramedical staffs' in the Department of Clinical Oncology.

Adult↗
PubMed2004

Transcriptional induction of FosB/DeltaFosB gene by mechanical stress in osteoblasts.

Mechanical stress to bone plays a critical role in maintaining bone mass and strength. However, the molecular mechanism of mechanical stress-induced bone formation is not fully understood. In the present study, we demonstrate that FosB and its spliced variant DeltaFosB, which is known to increase bone mass by stimulating bone formation in vivo, is rapidly induced by mechanical loading in mouse hind limb bone in vivo and by fluid shear stress (FSS) in mouse calvarial osteoblasts in vitro both at the mRNA and protein levels. FSS induction of FosB/DeltaFosB gene expression was dependent on gadlinium-sensitive Ca(2+) influx and subsequent activation of ERK1/2. Analysis of the mouse FosB/DeltaFosB gene upstream regulatory region with luciferase reporter gene assays revealed that the FosB/DeltaFosB induction by FSS occurred at the transcriptional level and was conferred by a short fragment from -603 to -327. DNA precipitation assays and DNA decoy experiments indicated that ERK-dependent activation of CREB binding to a CRE/AP-1 like element (designated "CRE2") at the position of -413 largely contributed to the transcriptional effects of FSS. These results suggest that DeltaFosB participates in mechanical stress-induced intracellular signaling cascades that activate the osteogenic program in osteoblasts.

Alternative Splicing↗
PubMed2004

Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion.

Multiple myeloma (MM) expands in the bone marrow and causes devastating bone destruction by enhancing osteoclastic bone resorption in its vicinity, suggesting a close interaction between MM cells and osteoclasts (OCs). Here, we show that peripheral blood mononuclear cell-derived OCs enhanced growth and survival of primary MM cells as well as MM cell lines more potently than stromal cells, and that OCs protected MM cells from apoptosis induced by serum depletion or doxorubicin. OCs produced osteopontin (OPN) and interleukin 6 (IL-6), and adhesion of MM cells to OCs increased IL-6 production from OCs. In addition, IL-6 and OPN in combination enhanced MM cell growth and survival. However, the effects of OCs on MM cell growth and survival were only partially suppressed by a simultaneous addition of anti-IL-6 and anti-OPN antibodies and were completely abrogated by inhibition of cellular contact between MM cells and OCs. These results demonstrate that OCs enhance MM cell growth and survival through a cell-cell contact-mediated mechanism that is partially dependent on IL-6 and OPN. It is suggested that interactions of MM cells with OCs augment MM growth and survival and, thereby, form a vicious cycle, leading to extensive bone destruction and MM cell expansion.

Animals↗
PubMed2004

Monitoring behaviour of catabolic genes and change of microbial community structures in seawater microcosms during aromatic compound degradation.

The behaviour of microbial populations responsible for degradation of the aromatic compounds, phenol, benzoate, and salicylate, and changes of microbial community structures in seawater microcosms were analysed quantitatively and qualitatively using MPN-PCR and PCR-DGGE. The purpose of the study was to investigate the ecology of the entire microbial community during bioremediation. Bacterial populations possessing catechol 1,2-dioxygenase (C12O) DNA were evidently the primary degraders of phenol and benzoate, but others possessing catechol 2,3-dioxygenase (C23O) DNA increased to enhance substrate degradation under high-load conditions when the substrates were present for long periods. However, salicylate degradation was evidently facilitated by specific bacterial populations possessing C23O DNA. PCR-DGGE analyses suggested that bacterial populations already relatively dominant in the original microcosm contributed to phenol degradation. Bacteria composing a minor fraction of the original population apparently increased and contributed to benzoate degradation. Bacterial populations possessing C23O DNA were responsible for salicylate degradation, however, and different degrading bacteria were evidently selected for, depending on the initial salicylate concentration. Microbial community structure tended to be simplified by aromatic compound degradation. Thus, microbial monitoring can elucidate the behaviour of bacterial populations responsible for aromatic compound degradation and be used to assess the effects of bioremediation on intact microbial ecosystems.

Bacteria↗