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Biomedical subjects

H Ueno

Publications and source records attributed to H Ueno.

At least 19 recordsLinked to original sources

Interleukin 10 and transforming growth factor beta contribute to the development of experimentally induced allergic conjunctivitis in mice during the effector phase.

AIM: To investigate the involvement of interleukin (IL)10 and transforming growth factor (TGF) beta in the development of experimentally induced allergic conjunctivitis in mice. METHODS: Balb/c mice were actively sensitised with ragweed in alum, and then challenged with ragweed in eye drops after 10 days. 24 h later, the conjunctivas, spleens and blood were collected for histological and cytokine expression analyses, proliferation and cytokine production assays and measurement of immunoglobulin (Ig) levels. Mice developing experimentally induced allergic conjunctivitis were injected intraperitoneally with 200 microg of anti-IL10 or anti-TGF beta antibodies at 0, 2, 4, 6 and 8 days (induction phase treatment) or 500 microg of antibodies 2 h before ragweed challenge (effector phase treatment). Normal rat IgG was used for control injections. RESULTS: Treatment with either anti-IL10 or anti-TGF beta antibodies during the induction phase did not affect eosinophil infiltration into the conjunctiva. By contrast, treatment with either antibody during the effector phase suppressed infiltration. During the effector phase, treatment with anti-TGF beta antibody, but not the anti-IL10 antibody, markedly up regulated proliferation and Th2 cytokine production by splenocytes. IL1alpha levels in the conjunctiva were reduced after treatment with either antibody; in addition, eotaxin and tumour necrosis factor alpha levels were reduced after treatment with antibody to TGF beta. CONCLUSIONS: IL10 and TGF beta do not have immunosuppressive roles in the development of experimentally induced allergic conjunctivitis. Rather, they augment the infiltration of eosinophils into the conjunctiva during the effector phase of experimentally induced allergic conjunctivitis.

Adoptive Transfer↗

Involvement of programmed death-ligand 2 (PD-L2) in the development of experimental allergic conjunctivitis in mice.

BACKGROUND/AIM: Involvement of programmed death-1 (PD-1) and its ligands has been demonstrated in experimental allergic airway disease. Here, the authors aimed to examine whether PD-1 and its ligands are involved in the development of experimental allergic conjunctivitis (EC) in mice. METHODS: EC was induced in Balb/c mice by active immunisation with short ragweed pollen (RW) in alum. 10 days later (day 10), the mice were challenged with eye drops containing RW. 24 hours after the challenge, conjunctivas, spleens, and sera were harvested for histological analysis, cytokine assays, and measurement of RW specific Ig levels. The actively immunised mice were treated with anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies (Abs), or normal rat immunoglobulin G (nrIgG) during either the induction (day 0, 2, 4, 6, and 8) or the effector (2 hours before RW challenge on day 10) phase. RESULTS: Ab treatment during the induction phase did not affect eosinophil infiltration although immune responses were modulated. In contrast, treatment with anti-PD-L2 Ab, but not anti-PD-1 or anti-PD-L1 Ab, during the effector phase significantly increased eosinophil infiltration into the conjunctiva without affecting systemic immune responses. CONCLUSIONS: Similar to allergic airway inflammation, PD-L2 is involved in the development of EC during the effector phase but not the induction phase.

Ambrosia↗

Immobility reduces muscle fiber necrosis in dystrophin deficient muscular dystrophy.

Duchenne/Becker muscular dystrophy is a progressive muscle disease, which is caused by the abnormality of dystrophin. Spina bifida is characterized by paralysis of the feet, with most of the upper extremities not being affected. We report here on the first case of Becker muscular dystrophy coinciding with spina bifida. The muscle biopsy specimens of the patient showed dystrophic changes in upper extremities, but clearly less in lower extremities. The results show that the restriction of excessive exercise is important for dystrophin deficiency disease.

Child, Preschool↗

Inflammatory reaction following cataract surgery and implantation of acrylic intraocular lens in rabbits with endotoxin-induced uveitis.

PURPOSE: To investigate whether inflammatory responses are more severe in uveitic eyes than nonuveitic eyes when acrylic intraocular lens (IOL) is implanted after cataract surgery. METHODS: Clear lens removal (phacoemulsification and aspiration) was conducted and the hydrophobic acrylic IOL (AR40e, AMO) was implanted in adult albino rabbits. Just after the operation, rabbits were divided into two groups. One group (nine rabbits) received intravitreal injection of lipopolysaccharide (LPS, 200 ng/10 microl) into both eyes to induce endotoxin-induced uveitis (EIU) and the other group (nine rabbits) received intravitreal injection of phosphate-buffered saline (PBS, 10 microl) into both eyes as the control. Aqueous humour (AH) and IOLs were harvested 1, 3 , and 7 days after the intravitreal injection. The infiltrating cell number in AH was counted and the protein concentration of AH was measured. IOLs were evaluated morphologically. RESULTS: At 1 day after intravitreal injection, both the infiltrating cell number in AH and protein concentration of AH were significantly higher in the LPS-injected group than in the PBS-injected group. Similarly, more inflammatory cells attached to the surfaces of the IOLs in the LPS-injected group. However, 7 days later, inflammatory reactions subsided and no clear differences in any of the parameters examined were observed between the two groups. CONCLUSIONS: At 7 days after the operation, inflammatory reactions in eyes implanted with the hydrophobic acrylic IOLs were similar in uveitic eyes and nonuveitic eyes. The data suggest that the hydrophobic acrylic IOLs may be suitable for patients with uveitis.

Acrylic Resins↗

[Use of a balloon occlusion catheter for descending aortic aneurysm after total arch replacement using the elephant trunk technique].

A 74-year-old man who had previously undergone prosthetic graft replacement of the total aortic arch using the elephant trunk technique and of the abdominal aorta was admitted to our hospital for surgical treatment of descending aortic aneurysm. Computed tomography (CT) on admission revealed descending aortic aneurysm of 6.5 cm in diameter, and the previously placed prosthetic graft was detected in the aneurysm. Surgery for the descending aorta was performed under femoro-femoral partial bypass. During the operation, a balloon occlusion catheter introduced through the right brachial artery into the 'elephant trunk' graft was inflated before the aneurysm was opened, then the previously placed prosthetic graft was cross-clamped and the descending aorta was replaced with a new prosthetic graft with usual fashion. The postoperative course was uneventful.

Aged↗

Quasielastic 3He(e,e'p)2H reaction at Q2 = 1.5 GeV2 for recoil momenta up to 1 GeV/c.

We have studied the quasielastic 3He(e,e(')p)2H reaction in perpendicular coplanar kinematics, with the energy and the momentum transferred by the electron fixed at 840 MeV and 1502 MeV/c, respectively. The 3He(e,e(')p)2H cross section was measured for missing momenta up to 1000 MeV/c, while the A(TL) asymmetry was extracted for missing momenta up to 660 MeV/c. For missing momenta up to 150 MeV/c, the cross section is described by variational calculations using modern 3He wave functions. For missing momenta from 150 to 750 MeV/c, strong final-state interaction effects are observed. Near 1000 MeV/c, the experimental cross section is more than an order of magnitude larger than predicted by available theories. The A(TL) asymmetry displays characteristic features of broken factorization with a structure that is similar to that generated by available models.

Journal Article↗

Measurement of the 3He(e,e'p)pn reaction at high missing energies and momenta.

Results of the Jefferson Lab Hall A quasielastic 3He(e,e'p)pn measurements are presented. These measurements were performed at fixed transferred momentum and energy, q=1502 MeV/c and omega=840 MeV, respectively, for missing momenta p(m) up to 1 GeV/c and missing energies in the continuum region, up to pion threshold; this kinematic coverage is much more extensive than that of any previous experiment. The cross section data are presented along with the effective momentum density distribution and compared to theoretical models.

Journal Article↗

Clonidine produces a dose-dependent impairment of baroreflex-mediated thermoregulatory responses to positive end-expiratory pressure in anaesthetized humans.

BACKGROUND: Perioperative hypothermia is common and results from anaesthesia-induced inhibition of thermoregulatory control. Hypothermia is blunted by baroreceptor unloading caused by positive end-expiratory pressure (PEEP), and is mediated by an increase in the vasoconstriction threshold. Premedication with clonidine impairs normal thermoregulatory control. We therefore determined the effect of clonidine on PEEP-induced hypothermia protection. METHODS: Core temperature was evaluated in patients undergoing combined general and epidural anaesthesia for lower abdominal surgery. They were assigned to an end-expiratory pressure of zero (ZEEP) or 10 cm H(2)O PEEP. The PEEP group was divided into three blinded subgroups that received placebo (Cl-0), clonidine 150 microg (Cl-150) and clonidine 300 microg (Cl-300) respectively. Placebo or clonidine was given orally 30 min before surgery. We evaluated core temperature and thermoregulatory vasoconstriction. We also determined plasma epinephrine, norepinephrine, angiotensin II concentrations and plasma renin activity. RESULTS: Core temperature after 180 min of anaesthesia was 35.1 (0.4) degrees C in the ZEEP group. PEEP significantly increased final core temperature to 35.8 (0.5) degrees C (Cl-0 group). Clonidine produced a linear, dose-dependent impairment of PEEP-induced hypothermia protection: final core temperatures were 35.4 (0.3) degrees C in the Cl-150 group and 35.0 (0.6) degrees C in the Cl-300 group. Similarly, clonidine produced a linear and dose-dependent reduction in vasoconstriction threshold: Cl-0, 36.4 (0.3) degrees C; Cl-150, 35.8 (0.3) degrees C; Cl-300, 35.4 (0.6) degrees C. Plasma norepinephrine, angiotensin II concentrations and renin activity were consistent with the thermoregulatory responses. CONCLUSION: Baroreceptor unloading by PEEP normally moderates perioperative hypothermia. However, clonidine premedication produces a linear, dose-dependent reduction in this benefit.

Adrenergic alpha-Agonists↗

Expression of mKirre, a mammalian homolog of Drosophila kirre, in the developing and adult mouse brain.

mKirre, a mammalian homolog of the Drosophila kirre, is expressed in bone marrow stromal cells and the brain. Although mKirre has been shown to support the hematopoietic stem cells, little is known about the function of mKirre in the brain. In the present study, to gain insights into the function of mKirre, we investigated the expression pattern of mKirre gene in the developing and adult mouse brain using in situ hybridization. In the adult brain, mKirre mRNA was highly expressed in the olfactory bulb, the piriform cortex, the cochlear nucleus, and the cerebellum. At embryonic day (E) 11.5, we could observe mKirre mRNA in the differentiating zones of various regions, such as the caudate-putamen, the geniculate body, the thalamus, the amygdala, and the brainstem. Its gene expression in these regions at E11.5 also persisted to the adult, in which its expression levels were much less prominent. After birth, we could first observe high expression of mKirre mRNA in the glomerular and mitral layers of the olfactory bulb, the cortical plate of the neocortex, the cochlear nucleus, and the molecular and granule cell layers of the cerebellum. In the hippocampus, its gene expression was first observed in the dentate gyrus at postnatal day 7. The spatiotemporal expression pattern of mKirre mRNA suggests important roles of mKirre in later developmental processes, especially the synapse formation.

Age Factors↗

A novel classification of tumour budding in colorectal cancer based on the presence of cytoplasmic pseudo-fragments around budding foci.

AIMS: Tumour budding is an adverse prognostic factor in colorectal cancer (CRC). We have investigated the significance of cytoplasmic fragments occurring in the immediate vicinity of tumour budding foci. METHODS AND RESULTS: Seventy-three CRCs with high-grade budding (> 10 budding foci in a x 20 objective field) were classified according to extent of budding (10-19 versus 20+ foci) and by the presence or absence of cytoplasmic fragments identified by immunostaining for cytokeratin. In serial sections, cytoplasmic fragments were shown to be dendritic cell processes in continuity with budding tumour cells and were renamed pseudo-fragments. Cytoplasmic pseudo-fragments, but not extent of budding, were associated with aberrant expression of beta-catenin (P = 0.045) and laminin-5 gamma2 (P < 0.0001), and with absent peritumoral lymphocytic infiltration (P = 0.0077). Cytoplasmic pseudo-fragments had a stronger association with infiltrating growth pattern (P = 0.0014) than extent of tumour budding (P = 0.014). There was no association between extent of budding and cytoplasmic pseudo-fragments (P = 0.12). CONCLUSIONS: Cytoplasmic pseudo-fragments may be a marker for an activated budding phenotype that is associated with cell motility and increased invasiveness in CRC and is independent of the extent of budding.

Adult↗

Fibrocartilaginous embolism in a chondrodystrophoid breed dog.

An 8-year-old intact male Shih Tzu dog was admitted with acute-onset tetraplegia. Magnetic resonance imaging showed an abnormality of the cervical intramedullary spinal cord. Histopathological examination of a spinal biopsy confirmed the presence of intravascular cartilaginous emboli. This is the first report of an antemortem diagnosis of fibrocartilaginous embolism in a chondrodystrophoid breed dog.

Animals↗

Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin.

NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given intravenously to patients with solid tumours every 3 weeks using an infusion pump at a rate of 10 mg DXR equivalent min(-1). The starting dose was 6 mg DXR equivalent m(-2), and the dose was escalated according to the accelerated titration method. A total of 23 patients participated in this study. Neutropenia was the predominant haematological toxicity, and grade 3 or 4 neutropenia was observed at doses of 50 and 67 mg m(-2). Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia. In the dose identification part of the study, DLTs were observed at a dose of 67 mg m(-2) (grade 4 neutropenia lasting more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion-related reactions were not observed in any cases. The C(5 min) and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics. Among the 23 patients, a partial response was obtained in one patient with metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m(-2) every 3 weeks.

Aged↗

Phase II study of S-1 in patients with advanced biliary tract cancer.

The aim of this study was to investigate the efficacy and safety of an oral fluoropyrimidine derivative, S-1, in patients with advanced biliary tract cancer. Patients with pathologically confirmed advanced biliary tract cancer, a measurable lesion, and no history of radiotherapy or chemotherapy were enrolled. S-1 was administered orally (40 mg m(-2) b.i.d.) for 28 days, followed by a 14-day rest period. A pharmacokinetic study was performed on day 1 in the initial eight patients. In all, 19 consecutive eligible patients were enrolled in the study between July 2000 and January 2002. The site of the primary tumour was the gallbladder (n=16), the extrahepatic bile ducts (n=2), and the ampulla of Vater (n=1). A median of two courses of treatment (range, 1-12) was administered. Four patients achieved a partial response, giving an overall response rate of 21.1%. The median time-to-progression and median overall survival period were 3.7 and 8.3 months, respectively. Although grade 3 anorexia and fatigue occurred in two patients each (10.5%), no grade 4 toxicities were observed. The pharmacokinetic parameters after a single oral administration of S-1 were similar to those of patients with other cancers. S-1 exhibits definite antitumour activity and is well tolerated in patients with advanced biliary tract cancer.

Administration, Oral↗

Measurement of the generalized forward spin polarizabilities of the neutron.

The generalized forward spin polarizabilities gamma(0) and delta(LT) of the neutron have been extracted for the first time in a Q2 range from 0.1 to 0.9 GeV2. Since gamma(0) is sensitive to nucleon resonances and delta(LT) is insensitive to the Delta resonance, it is expected that the pair of forward spin polarizabilities should provide benchmark tests of the current understanding of the chiral dynamics of QCD. The new results on delta(LT) show significant disagreement with chiral perturbation theory calculations, while the data for gamma(0) at low Q2 are in good agreement with a next-to-leading-order relativistic baryon chiral perturbation theory calculation. The data show good agreement with the phenomenological MAID model.

Journal Article↗

Phase II study of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer.

Gemcitabine has been reported to be a potent radiosensitiser in human pancreatic cell lines. This study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with gemcitabine for locally advanced pancreatic cancer. In all, 42 patients with pancreatic cancer that was unresectable but confined to the pancreatic region were treated with external-beam radiation (50.4 Gy in 28 fractions over 5.5 weeks) and weekly gemcitabine (250 mg m(-2), 30-min infusion). Maintenance gemcitabine (1000 mg m(-2) weekly x 3 every 4 weeks) was initiated 1 month after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. Of the 42 patients, 38 (90%) completed the scheduled course of chemoradiotherapy. The major toxicity was leucopenia and anorexia. There was one death attributed to duodenal bleeding and sepsis. The median survival time was 9.5 months and the 1-year survival rate was 28%. The median progression-free survival time was 4.4 months. In 35 patients with documented disease progression at the time of analysis, 34 (97%) showed distant metastasis as the cause of the initial disease progression. The chemoradiotherapy used in this study has a moderate activity against locally advanced pancreatic cancer and an acceptable toxicity profile. Future investigations for treatment with more systemic effects are warranted.

Adult↗

Q2 evolution of the neutron spin structure moments using a 3He target.

We have measured the spin structure functions g(1) and g(2) of 3He in a double-spin experiment by inclusively scattering polarized electrons at energies ranging from 0.862 to 5.058 GeV off a polarized 3He target at a 15.5 degrees scattering angle. Excitation energies covered the resonance and the onset of the deep inelastic regions. We have determined for the first time the Q2 evolution of Gamma(1)(Q2)= integral (1)(0)g(1)(x,Q2)dx, Gamma(2)(Q2)= integral (1)(0)g(2)(x,Q2)dx, and d(2)(Q2)= integral (1)(0)x(2)[2g(1)(x,Q2)+3g(2)(x,Q2)]dx for the neutron in the range 0.1< or =Q2< or =0.9 GeV2 with good precision. Gamma(1)(Q2) displays a smooth variation from high to low Q2. The Burkhardt-Cottingham sum rule holds within uncertainties and d(2) is nonzero over the measured range.

Journal Article↗