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Biomedical subjects

M Aoki

Publications and source records attributed to M Aoki.

At least 37 records · Page 2Linked to original sources

Angiogenic and antifibrotic actions of hepatocyte growth factor improve cardiac dysfunction in porcine ischemic cardiomyopathy.

Impairment of cardiac function in ischemic cardiomyopathy has been postulated to be due to the decrease in blood flow and increase in collagen synthesis. Therefore, an approach to alter them directly by means of a growth factor may open up a new therapeutic concept in ischemic cardiomyopathy. From this viewpoint, hepatocyte growth factor (HGF) is a unique growth factor with angiogenic and antifibrotic effects. Thus, we examined the feasibility of gene therapy using HGF plasmid DNA for ischemic cardiomyopathy. Human HGF plasmid DNA at a dose of 0.4 or 4 mg was injected into ischemic myocardium of pigs induced by ameroid constrictor with the NOGA system. At 1 month after injection, the ischemic area was significantly reduced in the HGF group, accompanied by a significant increase in capillary density and regional myocardial perfusion in the ischemic area (P<0.01). In contrast, a significant decrease in fibrotic area was observed in the HGF group, associated with a significant decrease in collagen I, III and TGF-beta synthesis as compared to the control group (P<0.01). Consistently, cardiac function was significantly improved in the 4 mg HGF group as compared to the control group (P<0.05). Overall, the present in vivo experiments demonstrated that intramyocardial injection of human HGF plasmid DNA in ischemic cardiomyopathy resulted in a significant improvement in cardiac function through an increase in blood flow and decrease in fibrosis. These favorable outcomes suggest potential utility to treat patients with ischemic heart disease using HGF gene transfer. Currently, a phase I study using human HGF plasmid DNA is ongoing to test the validity of this concept.

Animals↗

Top-quark mass measurement from dilepton events at CDF II.

We report a measurement of the top-quark mass using events collected by the CDF II detector from pp collisions at square root of s = 1.96 TeV at the Fermilab Tevatron. We calculate a likelihood function for the top-quark mass in events that are consistent with tt --> bl(-)nu(l)bl'+ nu'(l) decays. The likelihood is formed as the convolution of the leading-order matrix element and detector resolution functions. The joint likelihood is the product of likelihoods for each of 33 events collected in 340 pb(-1) of integrated luminosity, yielding a top-quark mass M(t) = 165.2 +/- 6.1(stat) +/- 3.4(syst) GeV/c2. This first application of a matrix-element technique to tt --> bl+ nu(l)bl'- nu(l') decays gives the most precise single measurement of M(t) in dilepton events. Combined with other CDF run II measurements using dilepton events, we measure M(t) = 167.9 +/- 5.2(stat) +/- 3.7(syst) GeV/c2.

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Measurement of the inclusive jet cross section using the kT algorithm in pp collisions at (square root s)=1.96 TeV.

We report on a measurement of the inclusive jet production cross section as a function of the jet transverse momentum in pp collisions at (square root s)=1.96 TeV using data collected with the upgraded Collider Detector at Fermilab in run II, corresponding to an integrated luminosity of 385 pb-1. The measurement is carried out for jets with rapidity 0.1</yjet/<0.7 and transverse momentum in the range 54<pjetT<700 GeV/c. Next-to-leading order perturbative QCD predictions are in good agreement with the measured cross section after the necessary nonperturbative parton-to-hadron corrections are included.

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Measurement of the dipion mass spectrum in decays.

We measure the dipion mass spectrum in X(3872)--> J/psipi(+) pi(-) decays using 360 pb(-1) of pp collisions at square root s= 1.96 TeV collected with the CDF II detector. The spectrum is fit with predictions for odd C-parity ((3)S(1), (1)P(1), and (3)D(J)) charmonia decaying to J/psipi(+) pi(-), as well as even C-parity states in which the pions are from rho(0) decay. The latter case also encompasses exotic interpretations, such as a D(0)D(*0) molecule. Only the (3)S(1) and J/psirho hypotheses are compatible with our data. Since (3)S(1) is untenable on other grounds, decay via J/psirho is favored, which implies C= +1 for the X(3872). Models for J/psi - rho different angular momenta L are considered. Flexibility in the models, especially the introduction of rho - omega interference, enables good descriptions of our data for both L = 0 and 1.

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Projection patterns of lamina VIII commissural neurons in the lumbar spinal cord of the adult cat: an anterograde neural tracing study.

This study was designed to characterize the morphology of commissural axons, with the goal of revealing some of the organizing principles of their projections in the lumbosacral cord. Axons were labeled anterogradely with biotinylated-dextran amine which was injected in the left lamina VIII and the adjoining parts of lamina VII in the lumbar segments L5-L6 in seven cats. After 3-4 weeks, commissural axons were well labeled throughout lumbosacral segments L1-S2. After crossing the midline at the injection level, labeled axons traveled rostrally and/or caudally in the contralateral ventral and lateral funiculi giving off multiple axon collaterals. The trajectories of 34 single axons were traced in their entirety from their points of origin to their distal ends. Most of these axons were thin (proximal diameter <3.5 microm) and short (<30 mm), and gave off 6 to 32 axon collaterals at short intercollateral distances (mean <2 mm) in the lumbosacral enlargement. Some thicker axons (diameter >3.5 microm) ascended as far as the thoracic level; these supplied only four to six collaterals at long intercollateral intervals ( approximately 6.5 mm). All of the axons except one projected unilaterally. The axons as a whole terminated throughout the contralateral ventral horn. However, axons that traveled in different parts of the white matter had different characteristic terminal arborizations. The collaterals of axons that traveled in the ventral funiculus terminated preferentially in laminae VII-VIII, while those in the lateral funiculus terminated in lamina IX. Although the collateral branching patterns differed from one axon to another, collaterals arising from a particular axon usually exhibited similar patterns at different rostrocaudal levels. These uniform collateral termination patterns indicate that the morphology of each neuron might be specifically related to its function. This may allow future studies to identify different functional types of commissural neurons on the basis of much less extensive reconstructions.

Animals↗

Search for Higgs bosons decaying to bb and produced in association with W bosons in pp collisions at square root of s = 1.96 TeV.

We present a search for Higgs bosons decaying into bb and produced in association with W bosons in pp collisions at square root of s = 1.96 TeV. This search uses 320 pb(-1) of the data set accumulated by the upgraded Collider Detector at Fermilab. Events are selected that have a high-transverse momentum electron or muon, missing transverse energy, and two jets, at least one of which is consistent with the hadronization of a b quark. Both the number of events and the dijet mass distribution are consistent with standard model background expectations, and we set 95% confidence level upper limits on the production cross section times branching ratio for the Higgs boson or any new particle with similar decay kinematics. These upper limits range from 10 pb for mH = 110 GeV/c2 to 3 pb for mH = 150 GeV/c2.

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Evidence for the exclusive decay B(c)+- --> J/psi pi+- and measurement of the mass of the B(c)+- meson.

We report the first evidence for a fully reconstructed decay mode of the B(c)+- meson in the channel B(c)+- --> J/psi pi+-, with J/psi --> mu+ mu-. The analysis is based on an integrated luminosity of 360 pb(-1) in pp collisions at 1.96 TeV center of mass energy collected by the Collider Detector at Fermilab. We observe 14.6 +/- 4.6 signal events with a background of 7.1 +/- 0.9 events, and a fit to the J/psi pi+-mass spectrum yields a B(c)+- mass of 6285.7 +/- 5.3(stat) +/- 1.2(syst) MeV/c2. The probability of a peak of this magnitude occurring by random fluctuation in the search region is estimated as 0.012%.

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Search for charged Higgs bosons from top quark decays in pp collisions at square root s=1.96 TeV.

We report the results of a search for a charged Higgs boson in the decays of top quarks produced in pp collisions at a center-of-mass energy of 1.96 TeV. We use a data sample corresponding to an integrated luminosity of 193 pb-1 collected by the upgraded Collider Detector at Fermilab. No evidence for charged Higgs production is found, allowing 95% C.L. upper limits to be placed on BR(t-->H+b) for different charged Higgs decay scenarios. In addition, we present in the minimal supersymmetric standard model (mH+/-, tanbeta) plane the first exclusion regions with radiative and Yukawa coupling corrections.

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Precision top-quark mass measurement in the lepton+jets topology in p p collisions at square root s=1.96 TeV.

We report two measurements of the top-quark mass M(top) using the CDF II detector at the Fermilab Tevatron in a 318 pb(-1) data sample of tt events in the lepton+jets final state. One method uses an event-based likelihood technique resulting in M(top) = 173.2(-2.4)(+2.6)(stat) +/- 3.2(syst) GeV/c2 or 173.2(-4.0)(+4.1) GeV/c2. The second method reconstructs a top-quark mass in each event using the measured invariant mass of the hadronically decaying W boson to constrain the jet energy scale to obtain a value for M(top)of 173.5(-3.6)(+3.7)(stat) +/- 1.3(syst) GeV/c2 or 173.5(-3.8)(+3.9) GeV/c2 . We take the latter, which is more precise, as our result.

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Search for neutral Higgs bosons of the minimal supersymmetric standard model decaying to tau pairs in pp collisions at square root of s = 1.96 TeV.

We present a search for neutral supersymmetric Higgs bosons decaying to tau pairs produced in pp collisions at square root of s = 1.96 TeV. The data, corresponding to 310 pb(-1) integrated luminosity, were collected with the Collider Detector at Fermilab in run II of the Tevatron. No significant excess above the standard model backgrounds is observed. We set exclusion limits on the production cross section times branching fraction to tau pairs for Higgs boson masses in the range from 90 to 250 GeV/c2.

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Prevention of abdominal aortic aneurysms by simultaneous inhibition of NFkappaB and ets using chimeric decoy oligonucleotides in a rabbit model.

Abdominal aortic aneurysm (AAA) is one of the major vascular diseases caused by atherosclerosis. Because treatment for AAA mainly consists of surgery to prevent deaths from AAA rupture and there is a conspicuous absence of alternative therapeutic strategies, the development of minimally invasive treatment is needed. To develop a novel therapeutic approach, we examined the simultaneous inhibition of the transcription factors NFkappaB and ets, which regulate inflammation and matrix degradation, in a rabbit AAA model. In this study, we employed chimeric decoy oligodeoxynucleotides (ODN), containing the consensus sequences of both the NFkappaB- and ets-binding sites, to inhibit both the transcription factors simultaneously. Using a delivery sheet, we examined the inhibitory effect of chimeric decoy ODN on aortic dilatation. Ultrasound and angiographic analysis demonstrated that treatment with chimeric decoy ODN significantly prevented the progression of elastase-induced aortic dilatation. The inhibitory effect of chimeric decoy ODN on aortic dilatation was also confirmed by histological studies. Treatment with chimeric decoy ODN reduced the activities of matrix metalloproteinase (MMP)-2 and MMP-9 and markedly inhibited the proteolysis of elastin as compared to scrambled decoy ODN. Interestingly, treatment with chimeric decoy ODN also suppressed VCAM-1 and MCP-1 gene expression, leading to inhibition of macrophage infiltration in the adventitia and media. The present study in a rabbit model provides a novel strategy to treat AAA by the simultaneous inhibition of both NFkappaB and ets using chimeric decoy ODN. Further modification of chimeric decoy ODN would be useful to treat AAA as a decoy-based therapy.

Animals↗

Disorder of the saliva melatonin circadian rhythm in patients with Meniere's disease.

OBJECTIVES: Stress is involved in the development of symptoms of Meniere's disease (MD). Stress-related disease has been reported to be associated with disorders in the circadian rhythm of melatonin (MEL) which regulates that rhythm. We therefore investigated MEL circadian rhythm of patients with MD. PATIENTS AND METHODS: A comparison of 13 MD patients was made with age-matched controls. Saliva samples were collected every 3 h. A statistical analysis of the circadian rhythm of saliva MEL was performed for a circadian rhythm by the fit of a 24- and 12-h composite cosine model. In addition, we assessed the stress and depression status of the two groups. RESULTS: The rhythmic amplitude of MEL in the MD group was significantly lower than that in the control group (P < 0.05). The acrophase in the MD group was significantly earlier than that in the control group (P < 0.05). MD patients had significantly higher stress score and depression score than control subjects (P < 0.05). The amplitude in MD patients had no significant correlation with their otologic clinical data. CONCLUSIONS: These results suggest that MD patients have a MEL deficiency, which is related to their stress and depression status rather than the otologic pathological status of MD.

Adult↗

Histological recovery of the hepatocytes is based on the redox system upregulation in the animal models of mutant superoxide dismutase (SOD)1-linked amyotrophic lateral sclerosis.

Histological rescue of superoxide dismutase1 (SOD1)-mutated hepatocytes from mutant SOD1 stress is investigated from the viewpoint of upregulation of the redox system [peroxiredoxin (Prx) and glutathione peroxidase (GPx)]. Histopathological and immunohistochemical studies using antibodies against PrxI/PrxII/GPxI were carried out on specimens from four different strains of animal models of mutant SOD1-linked familial amyotrophic lateral sclerosis (ALS). In the livers of the ALS animal models in the presymptomatic stage without motor neuron loss, both swollen and eosinophilic hepatocytes with vacuolation pathology were observed. After developing motor deficits, this swelling and vacuolation ceased to be apparent. In the terminal stage when severe motor neuron loss was observed, these hepatocytes recovered and appeared normal. In redox system-related immunohistochemical preparations, almost all of the normal hepatocytes expressed the redox system-related enzymes PrxI/PrxII/GPxI. In the presymptomatic stage, some hepatocytes did not express redox system-related enzymes. After clinical onset, over 75% of hepatocytes showed overexpression of PrxI/PrxII/GPxI, i. e., upregulation of the redox system. At the end stage, near normal PrxI/PrxII/GPxI expression was observed again in the hepatocytes. Redox system upregulation in SOD1-mutated hepatocytes rescues hepatocytes from the mutant SOD1 stress that leads to motor neuron death.

Amyotrophic Lateral Sclerosis↗

[Aortic valve replacement in elderly patients with small aortic annulus; is the indexed effective orifice area important?].

We sought to determine whether the small indexed effective orifice area (EOAI) increased mortality and morbidity after aortic valve replacement (AVR) in patients over 75 years of age. From May 1999 to July 2005, 77 patients underwent isolated AVR for aortic stenosis. They were divided into 3 groups (S-EOAI : EOAI < or = 0.7 cm2/m2, M-EOAI : 0.7 cm2/m2 <EOAI < or = 0.85 cm2/ m2, L-EOAI : 0.85cm2/m2 <EOAI) for evaluation. We examined the body surface area (BSA), EOAI, and the left ventricular (LV) mass index (LVMI). We found that patients with S-EOAI had less symptomatic improvement (p <0.05, vs L-EOAI) and LV mass regression (p< 0.01, vs L-EOAI). But, their average New York Heart Association (NYHA) class was improved significantly (2.3 +/- 0.8 vs 1.8 +/- 0.7 : preoperative vs postoperative, p=0.001). Furthermore, severe patient-prosthesis mismatch (PPM) had no significant negative impacts on the freedom of valve-related complications (75.1% : S-EOAI group vs 92.0% : L-EOAI group) and the 5-year survival (84.9% : S-EOAI group vs 87.8% : L-EOAI group). In elderly patients, the average NYHA class was 1.9 +/- 0.6 postoperatively (p<0.0001 vs preoperative) and the LVMI showed significant regression (p<0.0001) despite an average EOAI of 0.73 +/- 0.13 cm2/m2. It is important to consider whether the benefits of avoiding PPM overcome the drawbacks of other complicated techniques. In this study, we found that moderate PPM (0.7 cm2/m2 < or = EOAI) is acceptable to elderly patients.

Aged↗

[Effects of dexmedetomidine hydrochloride on postoperative sedation in cardiovascular surgery].

BACKGROUND: Postoperative assessment of brain damage in cardiovascular surgery is often obscured by sedatives. Therefore, early postoperative detection of brain attack and its treatment are also hampered. A newly approved sedative, dexmedetomidine hydrochloride has weak analgesic effect and no respiratory depressive effect. These characteristics allow early assessment of brain damage after surgery. In this report, we compared 2 sedatives, propofol and dexmedetomidine hydrochloride, in cardiovascular settings. SUBJECT AND METHODS: Both sedatives were initiated right after admission to the intensive care unit (ICU), followed by titrimetric method targeting for the sedation agitation scale (SAS) from 1 to 4. Thirty-five cases were included in dexmedetomidine hydrochloride group (DEX group) and 16 cases were included in propofol group (Prop group). RESULTS: Preoperative and operative demographic data were the same between the 2 groups. Conversion rate to another sedatives, and incidence of vasopressor or hypotensor use were both in the same proportion in both groups. Intubated time was the same in both groups. Both systolic and diastolic blood pressures were kept lower in DEX group than Prop group until 8 hours after ICU admission. Other hemodynamic measurements, heart rate, pulmonary artery pressure and cardiac index showed no statistical difference. SAS and Ramsay score were better in DEX group early after ICU admission, and remained better until 10 hours later. CONCLUSION: Dexmedetomidine hydrochloride has no major hemodynamic nor other side effects after cardiovascular surgery. Dexmedetomidine hydrochloride could be used as an effective agent for postoperative sedation and analgesia in cardiovascular settings.

Aged↗

Search for new high-mass particles decaying to Lepton pairs in pp collisions at square root s = 1.96 TeV.

A search for new particles (X) that decay to electron or muon pairs has been performed using approximately 200 pb(-1) of pp collision data at (square root) s = 1.96 TeV collected by the CDF II experiment at the Fermilab Tevatron. Limits on sigma(pp --> X)BR (X --> ll) are presented as a function of dilepton invariant mass m(ll) > 150 GeV/c2, for different spin hypotheses (0, 1, or 2). The limits are approximately 25 fb for m(ll) > GeV/c2. Lower mass bounds for X from representative models beyond the standard model including heavy neutral gauge bosons are presented.

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Search for [corrected] B0(s) --> mu+ mu- and B0(d) [corrected] --> mu + mu- decays in pp collisions with CDF II.

We report on a search for B0(s) --> mu+ mu- and B0(d) --> mu + mu- decays in pp collisions at square root(s) = 1.96 TeV using 364 pb(-1) of data collected by the CDF II detector at the Fermilab Tevatron Collider. After applying all selection requirements, we observe no candidates inside the B0(s) or B0(d) mass windows. The resulting upper limits on the branching fractions are B(B0(s) --> mu+ mu-) < 1.5 x 10(-7) and B(B0(d) --> mu+ mu-) < 3.9 x 10(-8) at 90% confidence level.

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