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Biomedical subjects

T Murakami

Publications and source records attributed to T Murakami.

At least 19 recordsLinked to original sources

Anisotropic x-ray emission from heliumlike Fe24+ ions aligned by resonant coherent excitation with a periodic crystal potential.

We have measured deexcitation x rays emitted from the resonant coherently excited 2(1)P(1) state of heliumlike Fe24+ ions of 423 MeV/amu, planar channeling through a Si crystal. Large anisotropy in the angular distribution of deexcitation x-ray emission is observed: the x-ray emission in the direction parallel to the channeling plane is favored by a factor of 2 compared to the perpendicular direction. This anisotropy originates from the direction of the periodic crystal field, which populates specific m states in resonant coherent excitation and aligns the excited states.

Journal Article↗

Three-dimensional resonant coherent excitation of nonchanneling ions in a crystal.

We have observed resonant coherent excitation (RCE) of H-like Ar(17+) ions traveling through a 1 microm-thick Si crystal at an energy of 391 MeV/u in the nonchanneling condition. A three-dimensional periodic array of atomic planes induces RCE of the nonchanneling ions. The high energy heavy ions together with the thin crystal allow us to observe this new RCE through the measurements of the charge-state distribution of the emerging ions. The observed resonances are much narrower than those of planar-channeling ions due to the absence of the large Stark shift caused by the planar potential.

Journal Article↗

Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors.

Antiangiogenic gene therapy is a promising strategy for cancer treatment, which generally requires highly efficient delivery systems. To date, success of this strategy has depended almost exclusively on the delivery of high titers of viral vectors, which can result in effective transgene expression. However, their cytotoxicity and immunogenicity are a major concern for clinical applications. Recent advances in delivery efficiency of naked DNA could potentially meet the requirement for both high transgene expression and minimal side effects. To investigate whether naked DNA can be used for antiangiogenic cancer therapy, an expression plasmid was generated that encodes a soluble form of fetal liver kinase-1 (Flk-1) gene, a receptor for vascular endothelial growth factor (VEGF). Hydrodynamic injection of this plasmid resulted in close to 0.1 mg/ml of soluble Flk-1 protein in mouse serum and blocked VEGF-driven angiogenesis in matrigel in vivo. The same delivery significantly suppressed the growth of two different pre-existing subcutaneous tumors, Renca renal cell carcinoma and 3LL lung carcinoma. CD31 immunohistochemistry revealed that the tumor-associated angiogenesis was also highly attenuated in soluble Flk-1-treated mice. Thus, expression of genes by hydrodynamics-based gene delivery of naked DNA appears to be a promising approach for antiangiogenic cancer gene therapy.

Animals↗

Application of a "black body" like reactor for measurements of quantum yields of photochemical reactions in heterogeneous systems.

We report for the first time an experimental application of the concept of a "black body" like reactor to measure quantum yields (Phi) of photochemical reactions in liquid-solid heterogeneous systems. A major advantage of this new method is its simplicity since the fractions of reflected and transmitted light are negligible due to reactor geometry and high optical density of the heterogeneous systems. The average quantum yield of a test reaction (phenol photodegradation) over TiO(2) (Degussa P25) as determined by this method was 0.14, identical to the quantum yield measured earlier for this same reaction under similar conditions by Salinaro and Serpone. We also report the quantum yield of phenol photodegradation over N-doped TiO(2) during photoexcitation at the fundamental absorption band (lambda = 365 nm; Phi = 0.12) and at the N-doping induced extrinsic absorption band (lambda = 436 nm; Phi = 0.08) of the photocatalyst.

Journal Article↗

Use of rapid diagnostic tests for malaria in an emergency situation after the flood disaster in Mozambique.

OBJECTIVES: To determine how diagnosis of malaria may be improved by combining the use of rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria with clinical diagnosis by the presence or history of fever compared with clinical diagnosis alone in emergency situations with flood-affected displaced populations in Mozambique. STUDY DESIGN: A cross-sectional study conducted at the emergency outpatient clinic in a village in the Chòkwè district of Gaza Province, 3 weeks after Cyclone Eline hit Mozambique in February 2000. METHODS: A hundred and thirty children aged less than 15 years with clinical malaria were selected for examination by RDT and fluorescent microscopy using acridine orange as a reference test. The diagnosis of clinical malaria was made by a history of fever in the last three days or axillary temperature above 37.0 degrees C at the time of attending the emergency outpatient clinic. Two positive predictive values were calculated; RDTs combined with clinical diagnosis and clinical diagnosis alone. RESULTS: Positive predictive values of RDTs combined with clinical diagnosis by the presence of fever or history of fever were 87.6% (92/105) (95% confidence interval (CI) 80.8-92.8) compared with 74.6% (97/130) (95% CI 66.2-81.8) for clinical diagnosis alone. Five patients were diagnosed false negative. CONCLUSION: RDTs combined with clinical diagnosis has sufficient positive predictive value to be used in emergency situations, while RDTs could result in increasing failure to treat when they are used for decisions of treatment compared with clinical diagnosis alone.

Adolescent↗

Experimental signature of medium modifications for rho and omega mesons in the 12 GeV p+A reactions.

The invariant mass spectra of e+e- pairs produced in 12 GeV proton-induced nuclear reactions are measured at the KEK Proton Synchrotron. On the low-mass side of the meson peak, a significant enhancement over the known hadronic sources has been observed. The mass spectra, including the excess, are well reproduced by a model that takes into account the density dependence of the vector meson mass modification, as theoretically predicted.

Journal Article↗

Histone deacetylase inhibitor FK228 suppresses the Ras-MAP kinase signaling pathway by upregulating Rap1 and induces apoptosis in malignant melanoma.

Histone deacetylase (HDAC) inhibitors are expected to be effective for refractory cancer because their mechanism of action differs from that of conventional antineoplastic agents. In this study, we examined the effect of the HDAC inhibitor FK228 on malignant melanoma, as well as its molecular mechanisms. FK228 was highly effective against melanoma compared with other commonly used drugs. By comparing the gene expression profiles of melanoma cells and normal melanocytes, we defined a subset of genes specifically upregulated in melanoma cells by FK228, which included Rap1, a small GTP-binding protein of the Ras family. The expression of Rap1 mRNA and protein increased in FK228-treated melanoma cells in both a dose- and a time-dependent manner. A decrease in the phosphorylation of c-Raf, MEK1/2, and ERK1/2 was accompanied by an increase in Rap1 expression in both FK228-treated and Rap1-overexpressing cells. Inhibition of Rap1 upregulation by small interfering RNA (siRNA) abrogated the induction of apoptosis and suppression of ERK1/2 phosphorylation in FK228-treated melanoma cells. These results indicate that the cytotoxic effects of FK228 are mediated via the upregulation of Rap1. Furthermore, we found that Rap1 was overexpressed and formed a complex with B-Raf in melanoma cell lines with a V599E mutation of B-Raf. The siRNA-mediated abrogation of Rap1 overexpression increased the viability of these cells, suggesting that Rap1 is also an endogenous regulator of Ras-MAP kinase signaling in melanomas.

Animals↗

Topical suplatast tosilate (IPD) ameliorates Th2 cytokine-mediated dermatitis in caspase-1 transgenic mice by downregulating interleukin-4 and interleukin-5.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by elevated serum levels of IgE. AD is associated with Th2 cytokines including interleukin (IL)-4, IL-5, IL-13 and IL-10. Systemic administration of suplatast tosilate (IPD) is currently used to treat Th2 cytokine-mediated AD. OBJECTIVES: To evaluate the effect of topical IPD on skin lesions of AD using a genetically engineered AD mouse model (K14/caspase-1 transgenic mouse: KCASP1Tg). METHODS: IPD ointment (3%) and white petrolatum (WP) were applied to KCASP1Tg mice every other day from 6 to 14 weeks after birth. Histopathological analysis of skin lesions and measurement of mRNA expression of cytokines in skin lesions and spleen cells were carried out. We also compared changes in serum parameters between IPD-treated and WP-treated KCASP1Tg mice. RESULTS: WP-treated mice developed dermatitis at 8 weeks after birth. However, skin lesions in IPD-treated mice were limited. Histopathologically, skin lesions in WP-treated KCASP1Tg mice showed marked inflammatory changes with increased mast cell infiltration. However, mice treated with IPD showed minimum skin lesions with scarce mast cell infiltration. WP-treated KCASP1Tg mice had significant elevation in the serum levels of histamine, IgE and IL-18 as compared with IPD-treated KCASP1Tg mice. mRNA expression of IL-4 and IL-5 in the skin lesions from WP-treated KCASP1Tg mice was significantly higher than in those from IPD-treated mice. In the spleen, the expression of IL-4, IL-5 and interferon-gamma was significantly increased in WP-treated KCASP1Tg mice as compared with their IPD-treated counterparts. CONCLUSIONS: This study shows that topical therapy with IPD inhibits the expression of IL-4 and IL-5 and ameliorates skin manifestations in an AD mouse model, suggesting the potential usefulness of topical IPD for the treatment of AD.

Administration, Topical↗

Congenital multiple ocular defects with falciform retinal folds among Japanese black cattle.

To clarify the morphologic features of the ocular disease recently occurring among Japanese Black cattle in southern Kyushu, 6 globes from 3 Japanese Black cattle, between 11 and 20 months old (cow Nos. 1 to 3), were pathologically examined. Cow Nos. 1 and 2 were sired by the same Japanese Black bull, and cow No. 3 was sired by the ancestor (sire) of the former bull. The ocular lesions were pathologically similar to each other, except for the left eye of cow No. 1. The ocular lesions of 5 globes were characterized by microphthalmia, hypoplasia, and/or dysplasia of the lenses; persistence of the primary vitreous; and retinal dysplasia with total nonattachment. The left globe from cow No. 1 had no lens and severe hypoplasia and nonattachment of the retina. Because dysplastic retinal lesions that formed crescentic folds and a central column were the most characteristic features of the eyes, the falciform retinal fold with congenital nonattachment was the most likely disease entity. Although the cause of the ocular disease could not be clarified with the present study, an inherited ocular defect of the bull and its ancestor was suspected.

Animals↗

Development of MBR with reduced operational and maintenance costs.

To reduce MBR O&M costs, a new MBR process that conducts efficient simultaneous biological nitrogen and phosphorus removal (BNR) was developed. In the development of this process, various approaches were taken, including reduction of power demand, chemical consumption and sludge disposal costs. To address power demand reductions, air supply requirements for membrane cleaning were reduced. The process adopted an improved membrane that requires less air for cleaning than conventional membranes. It also introduced cyclic aeration, which alternately supplies washing air to the two series of membrane units. Adoption of biological phosphorus removal eliminated chemical costs for phosphorus removal and contributed to the reduction of sludge disposal costs. By combining these technologies, compared to conventional MBR processes, an approximately 27% reduction in O&M costs was achieved.

Bioreactors↗

Characteristics of estrogen decomposition by ozonation.

Since the natural estrogens 17 beta-estradiol (E2) and estron (E1), and the synthetic estrogen 17 alpha-ethynyl estradiol (EE2) have strong endocrine disrupting effects and the tendency to persist in effluent from wastewater treatment plants, effective measures are needed to remove them from wastewater. In this research, to gain an understanding of the characteristics of estrogen decomposition by ozonation, experiments were conducted using effluent from an actual wastewater treatment plant. In this experiment, estrogen was added to effluent at a concentration of 200 ng/l and 20 ng/l before the ozonation experiments. The results showed 90% or more of estrogen concentration and estrogenic activity of E2, El and EE2 to be removed at an ozone dose of 1 mg/l. At an ozone dose of 3 mg/l, the estrogen concentration and estrogenic activity of E2, El and EE2 in the treated water fell below the detection limit. The removal rate was not influenced by the kind of estrogen. No generation of byproducts with estrogenic activity was observed. The authors conclude that estrogen in secondary treated wastewater can be almost entirely removed at the practical ozone dose rate applied for the purpose of disinfection, which is up to about 5 mg/l.

Endocrine Disruptors↗

Inhibitors of the TGF-beta superfamily and their clinical applications.

The transforming growth factor-beta (TGF-beta) superfamily includes TGF-betas, activin, myostatin and bone morphogenetic proteins. Misregulation of the activity of TGF-beta family members is involved in pathogenesis of cancer, muscular dystrophy, obesity and bone and tooth remodeling. Natural inhibitors for the TGF-beta superfamily regulate fine-tuning of activity of TGF-beta family in vivo. In addition to natural inhibitors for the TGF-beta family, soluble forms of receptors for the TGF-beta family, blocking monoclonal antibodies and small chemical TGF-beta inhibitors have been developed. In this review, we summarize recent advances in our understanding of inhibitors for the TGF-beta superfamily and their medical applications.

Animals↗

Reduced amplitude of the sural nerve sensory action potential in PARK2 patients.

The authors performed nerve conduction studies in nine PARK2 and eight idiopathic Parkinson disease patients and found a significant reduction of sural sensory nerve action potential (SNAP) amplitude in eight PARK2 patients who mostly remained asymptomatic. These data suggest that sensory axonal neuropathy may be a common clinical feature of PARK2 and a reduced amplitude of sural SNAP could be a diagnostic indicator of PARK2.

Action Potentials↗

Influence of the cyclooctadepsipeptides PF1022A and PF1022E as natural products on the design of semi-synthetic anthelmintics such as emodepside.

The 24-membered cyclooctadepsipeptide (CODP) PF1022A, the active metabolite of the fungus imperfectus Mycelia sterilia (Rosellinia sp.) isolated from the plant Camellia japonica in Japan, is described as a powerful broad-spectrum anthelmintic natural product with low toxicity in animals. Further CODPs such as PF1022B, C, D and E have been isolated from the same culture and their structures have been established. Both PF1022A and PF1022E serve as valuable starting materials for the synthesis of semi-synthetic CODP derivatives with improved intrinsic anthelmintic potency and broad-spectrum activity. It was found that in most cases the di-substituted PF1022A derivatives showed a greater (or equal) activity by oral application against the gastrointestinal nematode Haemonchus contortus compared to the corresponding mono-substituted PF1022A analogues as exemplified by emodepside. In order to get additional information on the bioactive conformation, emodepside was transformed into its mono- and tetra-thionated derivatives by isosteric replacement. In the light of the increased efficacy of these derivatives against H. contortus or Trichostrongylus colubriformis, it has been suggested that the asymmetric conformation clearly influences the anthelmintic activity of CODPs. Although useful synthetic pathways are available today for the preparation of the semi-synthetic CODP emodepside, the fermentative production of its bis-para-nitro and bis-para-amino precursors could be the process used for its industrial-scale production in the future.

Animals↗

Reduction of a vascular endothelial growth factor receptor, fetal liver kinase-1, by antisense oligonucleotides induces motor neuron death in rat spinal cord exposed to hypoxia.

Vascular endothelial growth factor (VEGF) is reported to play a neuroprotective role through a VEGF receptor, fetal liver kinase-1 (Flk-1) in vitro. We investigated whether reduction of Flk-1 could induce motor neuron loss in rat spinal cord by inhibiting the expression of Flk-1 in rat spinal cord using antisense oligodeoxynucleotides (ODNs) against the Flk-1 receptor. Rat spinal cord was repetitively exposed to 12% hypoxia, and the change of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway and the mitogen-activated protein kinase kinase (MEK)/extracellular-signal-regulated kinase (ERK) pathway was examined. Intrathecal infusion of Flk-1 antisense ODNs for 7 days suppressed almost completely Flk-1 expression in the lumbar segment of the spinal cord and was followed by a hypoxic challenge with 12% oxygen for 1 h that was repeated for 7 more days. In the lumbar segment, we observed that reduced Flk-1 expression and hypoxic challenge for 7 days resulted in approximately 50% loss of motor neurons, in which the activation of Akt and ERK, that is, increased levels of phosphorylated-Akt and of phosphorylated-ERK by hypoxia, was markedly inhibited. In contrast, the reduction of Flk-1 expression alone did not induce motor neuron loss. These results suggest that VEGF exerts its protective effect on motor neurons against hypoxia-induced toxicity by the Flk-1 receptor through the PI3-K/Akt and the MEK/ERK signaling pathways.

Animals↗

Oculomotor nerve schwannoma mimicking ophthalmoplegic migraine.

Ophthalmoplegic migraine (OM) is a rare variant of migraine characterized by recurrent attacks of severe headache followed by oculomotor nerve palsy. The recent revision of the International Headache Classification has reclassified OM from a subtype of migraine, defined as a functional headache, to the neuralgia category. We describe a case of an 11-year-old girl with pathologically confirmed oculomotor nerve schwannoma who had been suffering from symptoms mimicking OM. For five years, she has been under treatment for OM, an initial diagnosis which was corroborated by brain magnetic resonance imaging (MRI). Usually, most OM attacks occur during one period in a lifetime and remit completely. In contrast, however, her attacks became more frequent and were not controlled by medication. After surgery, the frequency of OM attacks was reduced. From this experience, we hypothesize that optic nerve tumor is one condition that can mimic OM, without apparent signs suggestive of intracranial mass. To our knowledge, this is the first report to describe a pathologically confirmed case of oculomotor nerve schwannoma mimicking OM.

Child↗

Glycogen depletion in intrafusal fibres in rats during short-duration high-intensity treadmill running.

AIM: The recruitment patterns of the intrafusal and extrafusal fibres in the soleus (SOL) and extensor digitorum longus (EDL) muscles of rats were investigated during brief-intensity exercise by assaying their glycogen content histochemically. METHODS: Six adult male rats were assigned to each of four groups that ran up a 6 degrees incline on a motor-driven treadmill, at 40 m min(-1) for either 0.5, 1, 2, or 4 min. Six adult male rats in the control group did not run. Extrafusal and intrafusal fibres were classified by myosin ATPase staining. Optical densities for glycogen content were evaluated in serial periodic acid Schiff (PAS) stained-sections from the B and C regions of intrafusal fibres. RESULTS: The glycogen content of type IIA fibres in the SOL and EDL muscles decreased significantly in the early phase of exercise whereas the glycogen content of type I fibres in these muscles decreased later than that of type IIA fibres. The glycogen content of bag2 fibres decreased after 1 min of exercise in the SOL muscle and after 2 min of exercise in the EDL muscle. On the other hand, the glycogen content of bag1 and chain fibres decreased significantly after 2 min in the SOL muscle but not in the EDL muscle. CONCLUSION: The results suggest that during brief-intensity exercise, as the glycogen content of type IIA fibres is reduced earlier than that of type I fibres, bag2 fibres are most important early in this type of exercise.

Animals↗