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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 73 records · Page 4Linked to original sources

The first record of Dirofilaria immitis infection in a Humboldt penguin, Spheniscus humboldti.

Dirofilaria immitis infection is an important parastic disease in many mammals, especially canids, but has not been reported in bird hosts. Filarial worms were isolated from the lumen of the right atrium of the heart and the connective tissue of the lung of a captive female Humboldt penguin, Spheniscus humboldti, that died at a zoo in Japan. One of these worms was observed morphologically and identified as D. immitis by features such as 4 pairs of cephalic papillae, 1 pair of cervical papillae, esophagus divided into 2 regions, 4 pairs of pre-anal papillae, 5 pairs of post-anal papillae, and unequal spicules. In addition, the partial DNA sequence (234 bp) of mitochondrial CO / gene of the filarial worm was identical to that of D. immitis. This is the first report of D. immitis infection in a bird.

Animals↗

Trends of delays in tuberculosis case finding in Japan and associated factors.

SETTING: Nationwide tuberculosis (TB) registry in Japan, 1987-2002. OBJECTIVE: To clarify the trends of patient's delay (PD), doctor's delay (DD) and total delay (TD), their relation and factors associated with the delays. DESIGN: Longitudinal study on trends in delays. Among patients with symptomatic smear-positive pulmonary TB, those with long PD (> or =2 months), DD (> or =1 month) and TD (> or =3 months) were analysed. RESULTS: Long PD rates increased until around 1997, whereas long DD rates decreased markedly from 1995 to 1999. Long TD rates increased until 1997, and decreased slightly thereafter. Men aged 30-59 years had higher rates of long PD, and the long PD rates increased through the 16-year observation period. Day labourers receiving or applying for welfare benefit had the highest rate of long TD, 46.5% during 1995-2002. Teachers and medical doctors showed the greatest increase in long TD rates through the period. CONCLUSION: Long TD was influenced more by PD than DD, and showed an upward trend. However, the long TD rate has declined slightly owing to the recent reduction in long DD. The reduction in DD since 1995 occurred immediately after the introduction of new technology in bacteriological examinations.

Adolescent↗

Search for doubly charged Higgs bosons decaying to dileptons in pp collisions at square root of s=1.96 TeV.

We present the results of a search for doubly charged Higgs bosons (H+/-+/-) decaying to dileptons (ll(')) using approximately 240 pb(-1) of pp collision data collected by the CDF II experiment at the Fermilab Tevatron. In our search region, given by same-sign ll(') mass m(ll('))>80 GeV/c(2) (100 GeV/c(2) for ee channel), we observe no evidence for H+/-+/- production. We set limits on sigma(pp -->H++H---->l(+)l('+)l(-)l('-)) as a function of the mass of the H+/-+/- and the chirality of its couplings. Assuming exclusive same-sign dilepton decays, we derive lower mass limits on H(+/-+/-)(L) of 133, 136, and 115 GeV/c(2) in the ee, mumu, and emu channels, respectively, and a lower mass limit of 113 GeV/c(2) on H(+/-+/-)(R) in the mumu channel, all at the 95% confidence level.

Journal Article↗

Measurement of the tt production cross section in pp collisions at sqrt[s]=1.96 TeV using dilepton events.

We report a measurement of the tt production cross section using dilepton events with jets and missing transverse energy in pp collisions at a center-of-mass energy of 1.96 TeV. Using a 197+/-12 pb(-1) data sample recorded by the upgraded Collider Detector at Fermilab, we use two complementary techniques to select candidate events. We compare the number of observed events and selected kinematical distributions with the predictions of the standard model and find good agreement. The combined result of the two techniques yields a tt production cross section of 7.0(+2.4)(-2.1)(stat)+1.6-1.1(syst)+/-0.4(lum) pb.

Journal Article↗

New limit on the T-violating transverse muon polarization in K+-->pi0mu+nu decays.

A search for T-violating transverse muon polarization (P(T)) in the K+-->pi(0)mu(+)nu decay was performed using kaon decays at rest. A new improved value P(T)=-0.0017+/-0.0023(stat)+/-0.0011(syst) was obtained giving an upper limit |P(T)|<0.0050. The T-violation parameter was determined to be Imxi=-0.0053+/-0.0071(stat)+/-0.0036(syst) giving an upper limit |Imxi|<0.016.

Journal Article↗

Observation of the narrow state X(3872)-->J/psipi+pi- in pp collisions at sqaure root of s=1.96 TeV.

We report the observation of a narrow state decaying into J/psipi+pi- and produced in 220 pb(-1) of p p-bar collisions at =1.96 Tesqaure root of sV in the CDF II experiment. We observe 730+/-90 decays. The mass is measured to be 3871.3+/-0.7(stat)+/-0.4(syst) MeV/c2, with an observed width consistent with the detector resolution. This is in agreement with the recent observation by the Belle Collaboration of the X(3872) meson.

Journal Article↗

Search for B0s-->micro+micro- and B0d-->micro+micro- decays in pp collisions at square root s = 1.96 TeV.

We report on a search for B(0)(s)-->micro(+)micro(-) and B(0)(d)-->micro(+)micro(-) decays in pp collisions at square root of s=1.96 TeV using 171 pb(-1) of data collected by the CDF II experiment at the Fermilab Tevatron Collider. The decay rates of these rare processes are sensitive to contributions from physics beyond the standard model. One event survives all our selection requirements, consistent with the background expectation. We derive branching ratio limits of B(B(0)(s)-->micro(+)micro(-))<5.8x10(-7) and B(B(0)(d)-->micro(+)micro(-))<1.5x10(-7) at 90% confidence level.

Journal Article↗

Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer.

Oestrogen receptor-binding fragment associated gene 9, EBAG9, is an oestrogen-responsive gene that was identified in MCF-7 human breast carcinoma cell line. It is identical to RCAS 1, a cancer cell surface antigen possibly involved in immune escape. In the present study, we examined the expression of EBAG9/RCAS1 in human epithelial ovarian cancer using immunohistochemistry, immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). A total of 90 epithelial ovarian cancer cases were examined immunohistochemically by means of the antibodies for EBAG9 and ERalpha. The correlation between EBAG9 immunoreactivity and clinicopathological parameters was examined. mRNA expression of EBAG9 and ERalpha were evaluated by RT-PCR in 22 cases. The expression for EBAG9 and ERalpha was examined by immunoblotting in 12 ovarian cancer cell lines. EBAG9 immunoreactivity was detected in the surface and cytoplasm of carcinoma cells in 46 out of 90 cases (51.1%). EBAG9 expression was significantly higher in serous histology (P=0.0402) and advanced disease (P=0.0206). No significant relationship was detected between EBAG9 immunoreactivity and overall survival (P=0.689). There was a highly significant correlation between EBAG9 and ER immunoreactivity (P<0.0001). The EBAG9 mRNA was detected in 20 out of 22 cases. In all of the cases that were positive for ERalpha mRNA, they were also positive for EBAG9 mRNA. Immunoreactive band corresponding to EBAG9 was detected in 11 out of 12 of ovarian cancer cell lines, and was consistent with ERalpha expression. In conclusion, the wide distribution of EBAG9 and its relation to advanced disease suggest that this protein may play important roles in epithelial ovarian cancer.

Antigens, Neoplasm↗

Retroviral oncogenes and TOR.

Retroviruses have recruited the catalytic subunit of PI 3-kinase and its downstream target, Akt, as oncogenes. These viruses cause tumors in animals and induce oncogenic transformation in cell culture. The oncogenicity of these viruses is specifically inhibited by rapamycin; retroviruses carrying other oncogenes are insensitive to this macrolide antibiotic. Rapamycin is an inhibitor of the TOR (target of rapamycin) kinase whose downstream targets include p70 S6 kinase and the negative regulator of translation initiation 4E-BP. Emerging evidence suggests that the TOR signals transmitted to the translational machinery are essential for oncogenic transformation by the PI 3-kinase pathway.

Animals↗

Inhibition of neointimal hyperplasia after balloon injury by cis-element 'decoy' of early growth response gene-1 in hypercholesterolemic rabbits.

Early growth response factor-1 (Egr-1) is a transcription factor that is rapidly activated after vascular injury and thus might contribute to vascular proliferation and inflammation. We hypothesized that Egr-1 might therefore be a therapeutic target against restenosis. Hypercholesterolemic rabbits were intraluminally administered synthetic DNA as a 'decoy' against Egr-1 immediately after carotid artery balloon injury. Efficient transfection was confirmed by the delivery of a fluorescence-labeled decoy. Gel mobility-shift assay showed increased Egr-1 activity after balloon injury and its prevention by Egr-1 decoy transfection in vivo. Egr-1 decoy transfection attenuated early inflammation and proliferation and later neointimal hyperplasia. In addition, Egr-1 decoy transfection reduced gene expression and protein production of Egr-1-dependent genes such as platelet-derived growth factor-B, transforming growth factor-beta1, and monocyte chemoattractant protein-1. The Egr-1 pathway has an essential role in the pathogenesis of neointimal hyperplasia after balloon injury in hypercholesterolemic rabbits. This decoy strategy is a potential practical form of therapy for human restenosis.

Angioplasty, Balloon↗

Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound.

Although gene therapy might become a promising approach for central nervous system diseases, the safety issue is a serious consideration in human gene therapy. To overcome this problem, we developed an efficient gene transfer method into the adult rat brain based on plasmid DNA using a microbubble-enhanced ultrasound method, since microbubble-enhanced ultrasound has shown promise for transfecting genes into other tissues such as blood vessels. Using the microbubble-enhanced ultrasound method, luciferase expression was increased approximately 10-fold as compared to injection of naked plasmid DNA alone. Interestingly, the site of gene expression was limited to the site of insonation with intracisternal injection, in contrast to previous studies using viruses. Expression of the reporter gene, Venus, was readily detected in the central nervous system. The transfected cells were mainly detected in meningeal cells with intracisternal injection, and in glial cells with intrastriatal injection. There was no obvious evidence of tissue damage by microbubble-enhanced ultrasound. Overall, the present study demonstrated the feasibility of efficient plasmid DNA transfer into the central nervous system, providing a new option for treating various diseases such as tumors.

Animals↗

Effect of nifedipine on endothelial function in normotensive smokers: potential contribution of increase in circulating hepatocyte growth factor.

Calcium antagonists are reported to have protective effects on the endothelium in vitro and in vivo. Especially, nifedipine, among many calcium antagonists, was shown to improve endothelial dysfunction in patients with hypertension. However, no report has determined whether the improvement of endothelial dysfunction by nifedipine is due to direct effects or indirect effects such as its hypotensive effect. Thus, in this study, we evaluated the direct effects of nifedipine on smoking-induced endothelial dysfunction, since cigarette smoking itself is a major factor in damage of endothelial cells, as well as hypertension. We examined whether nifedipine improves endothelial function in 10 normotensive smokers without any risk factors for atherosclerosis. The subjects were treated with 20 mg nifedipine monotherapy (n = 10) or placebo (n = 10) for 4 weeks. Nifedipine did not affect blood pressure and heart rate of normotensive smokers. We measured forearm blood flow (FBF) by strain-gauge plethysmography after 2 and 4 weeks of treatment. Changes in vasodilator response to reactive hyperaemia were significantly improved in nifedipine-treated subjects (P < 0.05), while there was no significant change in FBP response in control subjects. Response to nitroglycerin was not changed in either group. Moreover, to evaluate the mechanisms of the direct effects of nifedipine on the endothelium, we focused on hepatocyte growth factor (HGF), which is a novel angiogenic growth factor with an antiapoptotic action on endothelial cells. Interestingly, serum HGF concentration in smokers treated with nifedipine was significantly elevated both at 2 and 4 weeks (P < 0.05). Overall, these results demonstrated direct effects of nifedipine in the improvement of endothelial dysfunction in normotensive smokers. The increase in serum HGF concentration by nifedipine might contribute to the improvement of endothelial dysfunction.

Adult↗

RNA editing of interleukin-12 receptor beta2, 2451 C-to-U (Ala 604 Val) conversion, associated with atopy.

BACKGROUND: The production of IgE in B lymphocytes is down-regulated by IFN-gamma. IL-12 induces IFN-gamma production by T lymphocytes and natural killer cells by binding to its specific receptor. RNA editing is a post-transcriptional modification. OBJECTIVE: Here we show that the RNA editing of IL-12 receptor (R) beta2 is associated with atopy. METHODS: Atopic patients and non-atopic healthy controls were studied. Fragments of IL-12R beta2 cDNA and genomic DNA were amplified and sequenced. Furthermore, the function of the IL-12R beta2 chain was investigated. RESULTS: Sequence analysis of the cDNA clones representing IL-12R beta2 mRNA transcripts revealed a C-to-U conversion at nucleotide 2451 (Ala 604 Val) on exon 13 in some atopic patients. Surprisingly, sequence analysis of their genomic DNA showed no 2451 C-to-T (Ala 604 Val) mutation. We concluded that the observed C-to-U mismatch in the cDNA clone is due to a post-transcriptional modification, RNA editing. The C-to-U conversion was observed in 21 (20.6%) of 102 atopic patients, whereas this conversion was observed in only 4 (3.8%) of 104 non-atopic subjects (P<0.001). IFN-gamma production by peripheral blood mononuclear cells (PBMCs) stimulated with IL-12 in the subjects with the C-to-U conversion was significantly lower than that in the subjects without the C-to-U conversion. In atopic patients with the C-to-U conversion, PBMCs faintly showed the tyrosine phosphorylation of Stat4, and the IgE production by PBMCs was not suppressed by IL-12 whereas it was suppressed by IFN-gamma. CONCLUSIONS: The RNA editing of IL-12R beta2, 2451 C-to-U (Ala 604 Val) conversion causes impairment of the IL-12 signal cascade and the subsequent reduction in IFN-gamma production, resulting in the impaired down-regulation of IgE production. This is the first report indicating that atopy is associated with RNA editing.

Case-Control Studies↗

Cerebral ganglioneuroblastoma in a golden retriever dog.

An 8-month-old Golden Retriever dog was euthanatized because of a large cerebral mass extending from the right frontal lobe to the thalamus that was composed of both mature and immature neuronal cells. The better differentiated cells had abundant eosinophilic cytoplasm with prominent Nissl substance and were generally positive for neurofilament and variably positive for synaptophysin. The generally smaller and less-differentiated cells were infrequently positive for proliferating cell nuclear antigen and were negative for any neuronal and glial markers. No apparent glial differentiation of the immature tumor cells was detected. Based on morphologic and immunohistochemical features, the diagnosis of cerebral ganglioneuroblastoma was made. This neoplasm is very rare in all species, especially in the central nervous system, and has never been reported previously in this site in a dog.

Animals↗

Measurement of prompt charm meson production cross sections in pp collisions at square root s = 1.96 TeV.

We report on measurements of differential cross sections dsigma/dp(T) for prompt charm meson production in ppmacr; collisions at sqrt[s]=1.96 TeV using 5.8+/-0.3 pb(-1) of data from the CDF II detector at the Fermilab Tevatron. The data are collected with a new trigger that is sensitive to the long lifetime of hadrons containing heavy flavor. The charm meson cross sections are measured in the central rapidity region |y|</=1 in four fully reconstructed decay modes: D0-->K-pi(+), D(*+)-->D0pi(+), D+-->K-pi(+)pi(+), D(+)(s)-->phipi(+), and their charge conjugates. The measured cross sections are compared to theoretical calculations.

Journal Article↗

Dysferlin mutations in Japanese Miyoshi myopathy: relationship to phenotype.

OBJECTIVE: To study dysferlin gene mutations and genotype-phenotype correlations in Japanese patients with Miyoshi myopathy (MM). BACKGROUND: MM is an autosomal recessive distal muscular dystrophy that arises from mutations in the dysferlin gene. This gene is also mutated in families with limb girdle muscular dystrophy 2B. METHODS: The authors examined 25 Japanese patients with MM. Genomic DNA was extracted from the peripheral lymphocytes of the patients. The PCR products of each of 55 exons were screened by single strand conformation polymorphism or direct sequencing from the PCR fragments. RESULTS: The authors identified 16 different mutations in 20 patients with MM; 10 were novel. Mutations in Japanese patients are distributed along the entire length of the gene. CONCLUSIONS: Four mutations (C1939G, G3370T, 3746delG, and 4870delT) are relatively more prevalent in this population, accounting for 60% of the mutations in this study. This study revealed that the G3370T mutation was associated with milder forms of MM and the G3510A mutation was associated with a more severe form.

Adult↗