Biomedical subjects

Kenji Ohmori

Publications and source records attributed to Kenji Ohmori.

18 recordsLinked to original sources

PubMed2006

Implementation of quantum gate operations in molecules with weak laser fields.

We numerically propose a way to perform quantum computations by combining an ensemble of molecular states and weak laser pulses. A logical input state is expressed as a superposition state (a wave packet) of molecular states, which is initially prepared by a designed femtosecond laser pulse. The free propagation of the wave packet for a specified time interval leads to the specified change in the relative phases among the molecular basis states, which corresponds to a computational result. The computational results are retrieved by means of quantum interferometry. Numerical tests are implemented in the vibrational states of the B state of I2 employing controlled-NOT gate, and 2 and 3 qubits Fourier transforms. All the steps involved in the computational scheme, i.e., the initial preparation, gate operation, and detection steps, are achieved with extremely high precision.

Journal Article↗

PubMed2006

Visualizing picometric quantum ripples of ultrafast wave-packet interference.

Interference fringes in vibrating molecules are a signature of quantum mechanics, but are often so short-lived and closely spaced that they elude visualization. We have experimentally visualized dynamical quantum interferences, which appear and disappear in less than 100 femtoseconds in the iodine molecule synchronously with the periodic crossing of two counterpropagating nuclear wave packets. The obtained images have picometer and femtosecond spatiotemporal resolution, representing a detailed picture of the quantum interference.

Journal Article↗

PubMed2006

Real-time observation of phase-controlled molecular wave-packet interference.

The quantum interference of two molecular wave packets has been precisely controlled in the B electronic state of the I2 molecule by using a pair of fs laser pulses whose relative phase is locked within the attosecond time scale and its real-time evolution has been observed by another fs laser pulse. It is clearly observed that the temporal evolution changes drastically as a function of the relative phase between the locked pulses, allowing us to read both amplitude and phase information stored in the wave functions of the molecular ensemble.

Journal Article↗

PubMed2006

Histamine H1 receptor-stimulated interleukin 8 and granulocyte macrophage colony-stimulating factor production by bronchial epithelial cells requires extracellular signal-regulated kinase signaling via protein kinase C.

BACKGROUND: Histamine stimulates the release of several cytokines, such as interleukin (IL)-8 and granulocyte macrophage colony-stimulating factor, from bronchial epithelial cells. However, the functional individual histamine receptor subtype and intracellular signaling in bronchial epithelial cells are poorly defined. METHODS: Using human primary epithelial cells and the NCI-H292 cell line, we examined the expression of histamine receptor subtypes and histamine-induced second messenger. We also evaluated the involvements of mitogen-activated protein kinase, protein kinase C (PKC) and epidermal growth factor receptor in cytokine expression caused by histamine. RESULTS: Histamine H1 receptor (H1R) was the only subtype expressed in both types of cells. Histamine elevated intracellular calcium ion without affecting cAMP levels. Histamine induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Histamine also phosphorylated PKC and myristoylated alanine-rich C kinase substrate. Ro-31-8220, a PKC inhibitor, and PD98059, a mitogen-activated protein/ERK kinase inhibitor, suppressed the histamine-induced ERK activation and the production of granulocyte macrophage colony-stimulating factor and IL-8. On the contrary, histamine had no effect on the phosphorylation of epidermal growth factor receptor, and its specific inhibitor AG1478 failed to inhibit the histamine-induced ERK activation. Olopatadine, an H1 antagonist, completely blocked the histamine-related responses, whereas H2 and H3 antagonists did not. Histamine also augmented the IL-8 production caused by IL-4 or tumor necrosis factor-alpha. CONCLUSIONS: The H1R-PKC-ERK pathway may play crucial roles in eliciting cytokine production from bronchial epithelial cells stimulated by histamine, leading to airway inflammation.

Bronchi↗

PubMed2006

Olopatadine suppresses the migration of THP-1 monocytes induced by S100A12 protein.

Olopatadine hydrochloride (olopatadine) is an antiallergic drug with histamine H(1) receptor antagonistic activity. Recently, olopatadine has been shown to bind to S100A12 which is a member of the S100 family of calcium-binding proteins, and exerts multiple proinflammatory activities including chemotaxis for monocytes and neutrophils. In this study, we examined the possibility that the interaction of olopatadine with S100A12 inhibits the proinflammatory effects of S100A12. Pretreatment of olopatadine with S100A12 reduced migration of THP-1, a monocyte cell line, induced by S100A12 alone, but did not affect recombinant human regulated upon activation, normal T cell expressed and secreted (RANTES)-induced migration. Amlexanox, which also binds to S100A12, inhibited the THP-1 migration induced by S100A12. However, ketotifen, another histamine H(1) receptor antagonist, had little effect on the activity of S100A12. These results suggest that olopatadine has a new mechanism of action, that is, suppression of the function of S100A12, in addition to histamine H(1) receptor antagonistic activity.

Aminopyridines↗

PubMed2005

The effects of olopatadine hydrochloride on the number of scratching induced by repeated application of oxazolone in mice.

It is suggested that atopic dermatitis is a skin disease associated with itching as subjective symptoms, and histamine H(1) receptor antagonists are used in order to prevent the itching, and the deterioration for scratch by itching. Histamine H(1) receptor selective anti-histamine olopatadine hydrochloride (olopatadine; Allelock shows consistent efficacy and safety in the treatment of allergic disorders. We investigated the possible efficacy of olopatadine on the number of scratching induced by repeated application of oxazolone in BALB/c mice. The repeated treatment of olopatadine significantly inhibited the ear swelling and the increased number of scratching. It significantly inhibited the increased production of interleukin (IL)-4, IL-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lesioned ear. Moreover, it significantly inhibited the increased production of nerve growth factor (NGF) and substance P. On the other hand, loratadine, bepotastine and chlorpheniramine did not inhibit the ear swelling and the increased number of scratching. These results indicate that olopatadine inhibited not only the increased production of cytokines but also NGF and substance P unlike other histamine H(1) receptor antagonists. It was suggested that olopatadine suppressed the increased number of scratching by the anti-inflammatory effects. Therefore, olopatadine appears to exert additional biological effects besides its blockade of a histamine H(1) receptor.

Animals↗

PubMed2005

Effect of olopatadine and other histamine H1 receptor antagonists on the skin inflammation induced by repeated topical application of oxazolone in mice.

Histamine H1 receptor antagonists have long been prescribed for atopic dermatitis as an adjuvant therapy with topical therapy by local applied steroids. Olopatadine is one of the second-generation histamine H1 receptor antagonists that are treated for allergic disorders. We investigated that the effect of olopatadine on oxazolone-induced chronic contact hypersensitivity response in BALB/c mice compared with other histamine H1 receptor antagonists loratadine, cetirizine and fexofenadine. The chronic contact hypersensitivity induced by repeated application of oxazolone was treated with olopatadine and other histamine H1 receptor antagonists at the effective doses on histamine-induced paw edema in mice. The effects of these drugs in the oxazolone-induced model were quantified by measurements of ear swelling, and levels of cytokines in the lesioned ear. Olopatadine significantly inhibited the ear swelling and the increased production of IL-4, IL-1beta, IL-6, GM-CSF and NGF in the lesioned ear. On the other hand, the other histamine H1 receptor antagonists did not significantly suppress the increase in ear thickness. Moreover, they did not affect the production of cytokines in the lesioned ear. These results indicate that olopatadine appears to exert additional biological effects besides its blockade of the histamine H1 receptor.

Animals↗

PubMed2005

Directed self-assembly of Ge nanostructures on very high index, highly anisotropic Si(hkl) surfaces.

Families of very high-index planes, such as those which bifurcate spontaneously to form a hill-and-valley structure composed of opposing facets, provide natural templates for the directed growth of position-controlled self-organized nanostructures with shapes determined by the facet width ratio R. For example, deposition of a few ML of Ge on Si(173 100 373), corresponding to R(113/517) = 1.7, results in a field of 40-nm-wide Ge nanowires along [72 187] with a uniform period of 60 nm.

Anisotropy↗

PubMed2004

Histamine H1 receptor antagonist blocks histamine-induced proinflammatory cytokine production through inhibition of Ca2+-dependent protein kinase C, Raf/MEK/ERK and IKK/I kappa B/NF-kappa B signal cascades.

Histamine H1 receptor (H1R), a therapeutic target for alleviation of acute allergic reaction, may be also involved in mediating inflammatory responses via effects on cytokine production. However, the mechanisms whereby histamine induces cytokine production are poorly defined. In this study, we comprehensively investigated the signaling pathway involved in cytokine expression caused by histamine, using native human epidermal keratinocytes. We confirmed the expression of functional H1R by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and histamine-induced Ca(2+) elevation. Histamine induced concentration- and time-dependent production of granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-8 and IL-6, which was completely blocked by olopatadine, an H1 antagonist. Histamine activated the phosphorylation of protein kinase C (PKC), c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), I kappa B kinase (IKK), inhibitory kappa B (I kappa B)-alpha and nuclear factor-KB (NF-kappa B) p65, which was inhibited by Ro-31-8220, a PKC inhibitor. Also, Ro-31-8220 significantly suppressed the expression of these cytokines. BAPTA-AM, an intracellular Ca(2+) chelator, also reduced PKC phosphorylation and cytokine expression. PD98059, a MEK inhibitor, and BAY 11-8702, an I kappa B-alpha inhibitor, reduced ERK and NF-kappa B cascade activation, respectively, with little effect on PKC phosphorylation. PD98059 preferentially inhibited GM-CSF production whereas BAY 11-8702 prevented IL-8 and IL-6 production. Furthermore, in addition to the above cytokines, histamine stimulated the biosynthesis and/or release of numerous keratinocyte-derived mediators, which are probably regulated by the ERK or NF-kappa B cascades. Our study suggests that histamine activates Ca(2+)-dependent PKC isoforms that play crucial roles in the activation of Raf/MEK/ERK and IKK/I kappa B/NF-kappa B cascades, leading to up-regulation of cytokine expression. Thus, the anti-inflammatory benefit of H1 antagonists may be in part due to prevention of cytokine production.

Cells, Cultured↗

PubMed2004

Differential regulation of IL-4 expression and degranulation by anti-allergic olopatadine in rat basophilic leukemia (RBL-2H3) cells.

Olopatadine hydrochloride (olopatadine) is an anti-allergic drug that functions as a histamine H(1) antagonist and inhibits both mast cell degranulation and the release of arachidonic acid metabolites in various types of cells. In this study, we examined the ability of olopatadine to inhibit the expression of cytokine genes in vitro via high-affinity receptors for immunoglobulin E in mast cells, using a rat basophilic leukemia (RBL-2H3) cell line and an in vivo mouse model. Levels of gene expression in RBL-2H3 cells were determined by semi-quantitative RT-PCR, and serum interleukin-4 (IL-4) level in mice was quantified by ELISA. Olopatadine inhibited significantly the induction of IL-4 expression by mast cells both in vivo and in vitro. Olopatadine inhibited Ca(2+) influx through receptor-operated channels (ROC) without affecting Ca(2+) release from intracellular stores. Comparative analysis of olopatadine with other anti-allergic drugs and the ROC blocker SKF-96365 demonstrated that the potency of inhibition of Ca(2+) influx correlated with the degree of suppression of degranulation and arachidonic acid release. Inhibition of Ca(2+) influx decreased phosphorylation of p38 mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase, which participate in regulation of cytokine (e.g. IL-4) gene expression. However, the rank order of inhibition of Ca(2+) influx did not correspond to reduction of IL-4 expression, suggesting that an unknown mechanism(s) of action, in addition to inhibition of Ca(2+) influx, is involved in the expression of cytokines in mast cells.

Animals↗

PubMed2004

Properties of olopatadine hydrochloride, a new antiallergic/antihistaminic drug.

Olopatadine hydrochloride (CAS 140462-76-6, KW-4679, AL-4943A; hereinafter referred to as olopatadine) is a novel antiallergic drug that is a selective histamine H1 receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibits the tachykininergic contractions in guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine at doses of 0.03 mg/kg or higher reduces the symptoms of experimental allergic cutaneous responses and rhinoconjunctivitis in sensitized animals. Preclinical and clinical evaluations have demonstrated that olopatadine is a safe drug. After oral administration to healthy volunteers, olopatadine was rapidly and extensively absorbed. Unlike most other antiallergic drugs which are eliminated via hepatic metabolism, olopatadine is mainly excreted into urine. Olopatadine did not affect cytochrome P450 activities in human liver microsomes and consequently drug-drug metabolic interactions are unlikely. In double-masked clinical trials, olopatadine was shown to be effective at alleviating symptoms of allergic diseases. The drug (Allelock) was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, cutaneous pruritus, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. An ophthalmic solution of olopatadine is also useful for the treatment of allergic conjunctivitis: this formulation (Patanol) was approved in the USA and the European Union for the treatment of seasonal and perennial allergic conjunctivitis in 1996 and 2002, respectively.

Animals↗

PubMed2004

[Recent development of new drugs for the treatment of allergic diseases].

Due to the prevalence of allergic diseases such as bronchial asthma, allergic rhinoconjunctivitis and dermallergosis, efforts at the discovery of novel and effective medications for prevention and treatment of these conditions have been reinforced. Recently, it has been recognized that these allergic diseases are a chronic inflammatory disorder of the lower and upper airways and skin. In this article, we reviewed the recent development of the following new antiallergic therapies: anti-Th2 cytokine antibodies, decoy receptors, receptor antibodies, anti-IgE antibodies, anti-cell adhesion molecules antibodies, antisense oligonucleotides, keratinocyte modulators, inhibitors of phosphodiesterase 4, tachykinin receptor antagonists, and anti-histaminic drugs. Most of these new agents are aimed to inhibit various components of allergic inflammation. The future use of allergic disease therapies hold great promise and excitement.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2003

High-precision molecular wave-packet interferometry with HgAr dimers.

Molecular wave-packet (WP) interferometry has been demonstrated in the A electronic state of the HgAr van der Waals complex with two time-delayed UV fs pulses at 254 nm. The interferograms of three vibrational levels in the WP's display almost 100% fringe contrast as a function of the interpulse delay tau, which is tuned with sub-10 as stability and resolution. It is clearly observed that the three interferograms show their dephasing and rephasing within a single vibrational period, allowing us to prepare arbitrary relative populations of the three levels by adjusting a single parameter tau.

Journal Article↗

PubMed2003

Protective effects of benidipine on hydrogen peroxide-induced injury in rat isolated hearts.

We investigated the effects of benidipine (hydrochloride), a calcium antagonist, on hydrogen peroxide (H(2)O(2))-induced injury in Langendorff-perfused rat hearts. The hearts were aerobically perfused at a constant flow and exposed to H(2)O(2) (600 micromol L(-1)) for 4 min, resulting in the oxidative stress-induced myocardial dysfunction (e.g., decrease in the left ventricular developed pressure) and myocardial cell injury (e.g., increase in the release of lactate dehydrogenase). Pretreatment of the hearts with benidipine or nifedipine was performed for 20 min until the start of H(2)O(2) exposure. Benidipine at 1 nmol L(-1) and nifedipine at 10 nmol L(-1) decreased the myocardial contractility and perfusion pressure to a similar degree in the hearts under normal conditions. Benidipine (1 nmol L(-1)) significantly reduced the H(2)O(2)-induced myocardial damage. Nifedipine (10 nmol L(-1)) also tended to exhibit similar effects. Benidipine inhibited the increase in tissue lipid peroxidation induced by H(2)O(2). The results suggest that, in addition to the calcium antagonism, benidipine possesses other actions responsible for the cardioprotective effects, to which the antioxidant activity of benidipine may partly contribute.

Animals↗

PubMed2002

Pharmacological studies of diacerein in animal models of inflammation, arthritis and bone resorption.

Diacerein has proved to be effective in the treatment of osteoarthritis. We investigated the effects of diacerein in animal models of carrageenin-, zymosan-, or dextran-induced paw edema and adjuvant-induced arthritis and in ovariectomized rats. In acute inflammatory models, unlike classical nonsteroidal anti-inflammatory drugs such as naproxen and ibuprofen, diacerein inhibited the rat paw edema induced by various agents. In the adjuvant-induced arthritic rats, diacerein at 100 mg/kg/day significantly suppressed the paw edema and the increase in serum mucoprotein. Addition of 3 mg/kg/day naproxen to each diacerein (3, 10, 30 mg/kg/day) dose resulted in significantly greater anti-inflammatory activity than with naproxen alone. In the ovariectomized rats, diacerein (10, 100 mg/kg/day) also significantly prevented bone loss and reduced the serum alkaline phosphatase and decreased the excretion of urinary hydroxyproline. In addition, rhein (10, 30 microM) inhibited calcium release from mouse calvaria induced by interleukin-1 beta, prostaglandin E(2) and parathyroid hormone 1-34 human fragment. These findings indicate that diacerein is a novel anti-inflammatory drug with pharmacological properties different from those of classical nonsteroidal anti-inflammatory drugs and support the clinical investigation of the use of combination therapy with diacerein and nonsteroidal anti-inflammatory drugs in patients with not only osteoarthritis but also rheumatoid arthritis.

Animals↗

PubMed2002

Effects on the reactive oxygen species of erdosteine and its metabolite in vitro.

Erdosteine (CAS 84611-23-4) and its active metabolite (M1) decrease the luminol-dependent chemiluminescence (LDCL). In this study, the scavenging effects of erdosteine and M1 on each reactive oxygen species, hypochlorous acid (HOCl), hydrogen peroxide (H2O2) and superoxide anion (O2-), were investigated. M1 interacted with HOCl at high activity, whereas erdosteine exhibited low activity. Although erdosteine interacted with H2O2 only at 1 mmol/l, M1 could significantly decrease H2O2 (> 0.1 mmol/l). Erdosteine and M1 did not interact with O2-. These results suggest that M1 possesses scavenging activities against H2O2 and HOCl in vitro.

Acetylcysteine↗

PubMed2002

High-performance liquid chromatographic determination of oxatomide and its metabolite and its application to pharmacokinetic study in rat plasma.

Oxatomide (CAS 60607-34-3) is an antiallergic agent effective against allergic rhinitis, urticaria, pruritus dermatitis, eczema dermatitis and bronchial asthma. The aim of this study was to establish the method for simultaneously determining oxatomide and its major metabolite M-11 in human serum, human plasma and rat plasma by high-performance liquid chromatography (HPLC). The method was applied to study the influences of alimentation on pharmacokinetics of oxatomide in rats. After extracting oxatomide and its metabolite M-11 from human serum, human plasma or rat plasma with diethyl ether under alkaline condition, sulfuric acid was added to the organic layer and oxatomide and M-11 were back-extracted. The aqueous layers were analysed by HPLC equipped with a fluorimetric detector. The method was highly sensitive and precise for quantitation of oxatomide and M-11 in human serum, human plasma and rat plasma in the concentration range of 1 to 125 ng/ml. Plasma concentration of oxatomide decreased biphasically with an elimination half-life (T1/2) of 1.59 h after intravenous administration of oxatomide (1 mg/kg) to non-fasting male rats. After oral administration of oxatomide (30 mg/kg) to fasting male rats, plasma concentration of oxatomide increased rapidly, and reached the maximum concentration of 188 ng/ml (Cmax) at 1.0 h. Plasma concentration of oxatomide decreased monophasically. The T1/2 was 2.58 h. The bioavailability was 6.74%. Plasma concentration of M-11 increased rapidly, and reached Cmax of 64.3 ng/ml at 0.7 h, and decreased monophasically with T1/2 of 3.79 h. After oral administration of oxatomide to non-fasting male rats, plasma concentration of oxatomide reached Cmax of 378 ng/ml at 3.3 h. The T1/2 was 3.27 h and the bioavailability was 17.5%. The Cmax and AUC0-infinity of M-11 were larger than those after oral administration of oxatomide to fasting male rats. These results demonstrated the usefulness of this method for monitoring and basic examination of biological samples and the influence of alimentation on absorption of oxatomide. Determination of plasma oxatomide concentrations would provide a useful indication of therapeutic efficacy.

Administration, Oral↗

PubMed2002

Pharmacological, pharmacokinetic and clinical properties of olopatadine hydrochloride, a new antiallergic drug.

Olopatadine hydrochloride (olopatadine, 11-[(Z)-3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid monohydrochloride) is a novel antiallergic/histamine H1-receptor antagonistic drug that was synthesized and evaluated in our laboratories. Oral administration of olopatadine at doses of 0.03 mg/kg or higher inhibited the symptoms of experimental allergic skin responses, rhinoconjunctivitis and bronchial asthma in sensitized guinea pigs and rats. Olopatadine is a selective histamine H1-receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibited the tachykininergic contraction in the guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Olopatadine exerted no significant effects on action potential duration in isolated guinea pig ventricular myocytes, myocardium and human ether-a-go-go-related gene channel. Olopatadine was highly and rapidly absorbed in healthy human volunteers. The urinary excretion of olopatadine accounted for not less than 58% and the contribution of metabolism was considerably low in the clearance of olopatadine in humans. Olopatadine is one of the few renal clearance drugs in antiallergic drugs. Olopatadine was shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, pruritus cutaneous, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000. Ophthalmic solution of olopatadine was also approved in the United States for the treatment of seasonal allergic conjunctivitis in December, 1996 (Appendix: also in the European Union, it was approved in February 2002).

Animals↗