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Yasuhiro Suzuki

Publications and source records attributed to Yasuhiro Suzuki.

At least 19 recordsLinked to original sources

Molecular characterization of 8-methoxyfluoroquinolone resistance in a clinical isolate of methicillin-resistant Staphylococcus aureus.

BACKGROUND: Activity of gatifloxacin against clinical isolates of fluoroquinolone-resistant Staphylococcus aureus is more potent than that of other fluoroquinolones such as norfloxacin and levofloxacin. To date, few reports have described high-level resistance to gatifloxacin in clinical isolates of S. aureus, although in vitro studies have shown that mutations in both DNA gyrase and topoisomerase IV were required for gatifloxacin resistance in S. aureus. METHODS: Minimum inhibitory concentrations were determined for fluoroquinolones and other antimicrobials in a methicillin-resistant S. aureus isolate that was cultured from blood of a patient with septicemia. Fluoroquinolone resistance was characterized by DNA sequencing and microbiologic assay. RESULTS: The isolate showed high-level resistance to fluoroquinolones including an 8-methoxyfluoroquinolone, gatifloxacin (minimum inhibitory concentration 64 microg/ml). Amino acid mutations of Ser80Tyr and Glu84Lys in GrlA and Ser84Leu and Ser85Pro in GyrA were possibly related to this resistance in methicillin-resistant S. aureus HU2000-062, although efflux may play a minor role in resistance as well. CONCLUSION: GyrA and GrlA mutations mainly conferred to 8-methoxyfluoroquinolone resistance in this isolate.

Aged↗

[Usefulness of L-arginine infusion for status epilepticus in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes].

We encountered an 11-year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) who developed occipital lobe epilepsy at the age of 7 years and 4 months. Thereafter she had repeated status epilepticus associated with stroke-like episodes. Status epilepticus consisted of repetitive complex partial seizures with or without secondarily generalized tonic clonic seizures. The seizures did not respond to conventional anticonvulsive drugs, including diazepam, midazolam, phenytoin, lidocaine, chloral hydrate, and thiamylal sodium, and lasted for several hours (mean 9.5 hours). At the age of 11 years, intravenous infusion of L-arginine (0.5 g/kg body weight) was first given five hours after the onset of status epilepticus. The seizures and electroencephalographic abnormalities improved dramatically. After the introduction of L-arginine, in addition to shortened duration of status epilepticus (mean 3 hours), clinical recovery from the status epilepticus was prompt, and the average hospitalization periods could be shortened. There were no obvious adverse effects, including vomiting, hypotension, and urticaria. Our experience suggests that early intravenous administration of L-arginine may be useful in the treatment of status epilepticus associated with stroke-like episode in patients with MELAS.

Arginine↗

Effects of low-dose irradiation on enhancement of immunity by dendritic cells.

Low-doses of irradiation have been reported to have beneficial effects, particularly anti-tumor effects. In this paper, we show the effects of the low-dose irradiation on T cell activation induced by dendritic cells (DCs). DCs, which had been pre-irradiated at 0.02-1.0 Gy from a (137)Cs source, were cultured with allogeneic T cells, and the proliferation of T cells was then examined. The 0.05Gy-pre-irradiated DCs showed the highest proliferation capacity of T cells. The 0.05Gy-irradiation does not augment the expression of major histocompatibility complexes (MHCs) or costimulatory molecules on DCs, as with non-irradiated DCs or 1Gy-irradiated DCs, but does augment the production of IL-2, IL-12 and IFN-gamma DCs. These results suggest that the low-dose irradiation augments T cell-activation capacity through cytokine production by DCs, which might shift naïve helper T cells to Th1 cells.

Animals↗

p63 is upstream of IKK alpha in epidermal development.

The epidermis, the outer layer of the skin composed of keratinocytes, develops following the action of the transcription factor p63. The mouse Trp63 gene contains two promoters, driving the production of distinct proteins, one with an N-terminal trans-activation domain (TAp63) and one without (DeltaNp63), although their relative contribution to epidermal development is not clearly established. To identify the relative role of p63 isoforms in relation to IKKalpha, also known to be essential for epithelial development, we performed both molecular and in vivo analyses using genetic complementation in mice. We found that the action of TAp63 is mediated at the molecular level by direct and indirect transactivation of IKKalpha and Ets-1, respectively. We also found that DeltaNp63 upregulates IKKalpha indirectly, through GATA-3. Our data are consistent with a role for p63 directly upstream of IKKalpha in epithelial development.

Animals↗

Poly(ADP-ribose) polymerase-1 inhibition prevents eosinophil recruitment by modulating Th2 cytokines in a murine model of allergic airway inflammation: a potential specific effect on IL-5.

We recently used a murine model of allergic airway inflammation to show that poly(ADP-ribose) polymerase-1 (PARP-1) plays an important role in the pathogenesis of asthma-related lung inflammation. In this study, we show that PARP-1 inhibition, by a novel inhibitor (TIQ-A) or by gene deletion, prevented eosinophilic infiltration into the airways of OVA-challenged mice. Such impairment of eosinophil recruitment appeared to take place after IgE production. OVA challenge of wild-type mice resulted in a significant increase in IL-4, IL-5, IL-10, IL-13, and GM-CSF secretions. Although IL-4 production was moderately affected in OVA-challenged PARP-1(-/-) mice, the production of IL-5, IL-10, IL-13, and GM-CSF was completely inhibited in ex vivo OVA-challenged lung cells derived from these animals. A single TIQ-A injection before OVA challenge in wild-type mice mimicked the latter effects. The marked effect PARP-1 inhibition exerted on mucus production corroborated the effects observed on the Th2 response. Although PARP-1 inhibition by gene knockout increased the production of the Th1 cytokines IL-2 and IL-12, the inhibition by TIQ-A exerted no effect on these two cytokines. The failure of lung cells derived from OVA-challenged PARP-1(-/-) mice to synthesize GM-CSF, a key cytokine in eosinophil recruitment, was reestablished by replenishment of IL-5. Furthermore, intranasal administration of IL-5 restored the impairment of eosinophil recruitment and mucus production in OVA-challenged PARP-1(-/-) mice. The replenishment of either IL-4 or IgE, however, did not result in such phenotype reversals. Altogether, these results suggest that PARP-1 plays a critical role in eosinophil recruitment by specifically regulating the cascade leading to IL-5 production.

Animals↗

Delayed perfusion phenomenon in a rat stroke model at 1.5 T MR: an imaging sign parallel to spontaneous reperfusion and ischemic penumbra?

INTRODUCTION: Delayed perfusion (DP) sign at MR imaging was reported in stroke patients. We sought to experimentally elucidate its relation to spontaneous reperfusion and ischemic penumbra. METHODS: Stroke was induced by photothrombotic occlusion of middle cerebral artery in eight rats and studied up to 72 h using a 1.5 T MR scanner with T2 weighted imaging (T2WI), diffusion weighted imaging (DWI), and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI). Relative signal intensity (rSI), relative lesion volume (rLV), relative cerebral blood flow (rCBF), PWI(rLV)-DWI(rLV) mismatch (penumbra) and DP(rLV) were quantified and correlated with neurological deficit score (NDS), triphenyl tetrazolium chloride (TTC) staining, microangiography (MA) and histopathology. RESULTS: The rSI and rLV characterized this stroke model on different MRI sequences and time points. DSC-PWI reproduced cortical DP in all rats, where rCBF evolved from 88.9% at 1 h through 64.9% at 6 h to 136.3% at 72 h. The PWI(rLV)-DWI(rLV) mismatch reached 10+/-5.4% at 1 h, remained positive through 12 h and decreased to -3.3+/-4.5% at 72 h. The incidence and rLV of the DP were well correlated with those of the penumbra (p<0.01, r(2)=0.85 and p<0.0001, r(2)=0.96, respectively). Shorter DP durations and more collateral arterioles occurred in rats without (n=4) than with (n=4) cortex involvement (p<0.05). Rats without cortex involvement tended to earlier reperfusion and a lower NDS. Microscopy confirmed MRI, MA and TTC findings. CONCLUSIONS: In this rat stroke model, we reproduced clinically observed DP on DSC-PWI, confirmed spontaneous reperfusion, and identified the penumbra extending to 12h post-ischemia, which appeared interrelated.

Animals↗

De novo multiple endocrine neoplasia type 2B with noncardiogenic pulmonary edema as the presenting symptom.

Multiple endocrine neoplasia (MEN) type 2B is a rare hereditary disorder characterized by medullary thyroid carcinoma, pheochromocytoma, and neuroma. Early signs of MEN 2B are usually neuroma, gastrointestinal problems, and medullary thyroid carcinoma. Noncardiogenic pulmonary edema is rare as a presenting symptom. We report a 31-year-old male who was admitted to our hospital because of noncardiogenic pulmonary edema. He was 168 cm in height, weighed 55 kg, and had an arm span of 166 cm. No marfanoid habitus was evident, but thickened lips and tongue neuroma were present. Chronic constipation had been present since childhood, and the patient had a two-year history of untreated hypertension. Noncardiogenic pulmonary edema and toxic megacolon were noted, and abdominal computed tomography revealed bilateral adrenal tumors. Ultrasonography of the thyroid showed two mass lesions. Intubation and mechanical ventilation were performed because of severe hypoxemia. Endocrinological examinations showed high levels of serum and urinary fractionated catecholamines, serum calcitonin, serum carcinoembryonic antigen, and serum intact parathyroid hormone. It was suggested that the high level of catecholamine from pheochromocytoma had caused the pulmonary edema. RET gene analysis showed a codon 918 mutation in exon 16 resulting in an ATG (methionine) to ACG (threonine) substitution, but analysis of the patient's parents showed the wild type. Therefore, the patient was diagnosed as having de novo MEN 2B. He underwent laparoscopic bilateral adrenectomy and total thyroidectomy. However, the values of serum calcitonin and CEA did not decrease to the normal ranges. Patients with early-stage MEN 2B have distinct characteristics that can aid early detection of the disease, thus possibly allowing them to be saved.

Adrenal Gland Neoplasms↗

Treatment and transfer of emphysema by a new bone marrow transplantation method from normal mice to Tsk mice and vice versa.

We have recently established a new bone marrow transplantation (BMT) method in which bone marrow cells are injected into the intrabone marrow (IBM). In the present study, we used an animal model for emphysema (tight-skin [Tsk] mouse) to examine whether IBM-BMT could be used to treat emphysema in Tsk mice. IBM-BMT was carried out from C3H mice into Tsk mice (8-10 weeks old) that had already shown emphysema. Six months after transplantation, the lungs of all the Tsk mice treated with IBM-BMT [C3H-->Tsk] showed similar structures to those of normal mice, whereas the [Tsk-->Tsk] mice showed emphysema, as seen in age-matched Tsk mice. Next, we attempted to transfer emphysema from Tsk mice to C3H mice by IBM-BMT. Six months after IBM-BMT, the [Tsk-->C3H] mice showed emphysema. These results strongly suggest that emphysema in Tsk mice originates from defects of stem cells in the bone marrow.

Animals↗

Treatment of Japanese restless legs syndrome patients with cabergoline: an open clinical preliminary trial.

OBJECTIVE: To determine the effective dose of cabergoline in Japanese patients with restless legs syndrome (RLS). METHODS: Six cases of idiopathic RLS and three of RLS with Parkinson disease (PD) participated in an open clinical preliminary trial. All cases were diagnosed based on the clinical criteria of the International RLS Study Group. Three RLS cases (1.3%) were detected out of 229 consecutive cases with PD. RLS severity was evaluated with International RLS Study Group (IRLSSG) Rating Scale Version 2.2 before and one year after the treatment with cabergoline. RESULTS: For 6 idiopathic RLS patients, the IRLSSG questionnaire scores improved from 25.5+/-3.7 to 10.7+/-8.9 (p=0.028, Wilcoxon test) with 1 mg of daily cabergoline at the endpoint. For 3 RLS cases with PD, the score was 21.7+/-3.7 before the treatment, and RLS symptoms completely disappeared with 1 mg of cabergoline. One of RLS cases with PD required additional cabergoline later because of parkinsonism. No adverse event with cabergoline was reported in this study. CONCLUSION: One mg of daily cabergoline is effective in some Japanese patients of RLS.

Aged↗

Elevation of IL-12 p40 and its antibody in myasthenia gravis with thymoma.

We examined the serum levels of cytokines, interferon (IFN)-alpha, IFN-gamma, interleukin (IL)-4, IL-12 p40, and IL-12 p70; those that affect the T helper 1 and 2 balance in patients with myasthenia gravis (MG). Among the cytokines tested, only IL-12 p40, together with the serum titer of anti-IL-12 p40 antibody, was significantly elevated in MG with thymoma. Their elevation was independent of the histopathology of thymoma. Thymectomy decreased the levels of IL-12 p40 accompanied by the anti-acetylcholine receptor antibody, but not anti-IL-12 p40 antibodies. These data strongly suggest the association of IL-12 p40 and its autoantibody with the immunopathology of MG with thymoma.

Adolescent↗

Mechanisms underlying acceleration of blood flow recovery in ischemic limbs by macrophage colony-stimulating factor.

Recently we reported that macrophage colony-stimulating factor (M-CSF) can mobilize endothelial progenitor cells (EPCs) from the bone marrow into the peripheral blood, resulting in an increase in the number of blood vessels and augmentation of blood flow in the ischemia-induced legs. M-CSF accelerates neovascularization of ischemic lesions resulting from the mobilization of EPCs. In the present paper, we analyze the mechanisms underling the mobilization of EPCs by M-CSF. M-CSF augments the production of vascular endothelial growth factor (VEGF) from the bone marrow cells, especially from myeloid lineage cells. In vivo administration of anti-VEGF antibody abrogates both the acceleration of the recovery of blood flow in the ischemia-induced limbs by M-CSF and the augmentation of the mobilization of EPCs induced by M-CSF. These results suggest that the M-CSF contributes to rapid recovery of blood flow in ischemic lesions by mobilization of EPCs from the bone marrow through augmentation of VEGF production in the bone marrow and that the VEGF is mainly produced by myeloid lineage cells.

Animals↗

Edaravone diminishes free radicals from circulating neutrophils in patients with ischemic brain attack.

OBJECTIVE: Treatment with a free radical scavenger could be a new option for ischemic brain attack, however, little is known about the alteration of oxidative stress markers induced by edaravone, a novel free radical scavenger, in human ischemic brain attack. METHODS: We investigated the effects of edaravone on the oxidative stress markers in patients with ischemic brain attack. Twenty-one patients with ischemic brain attack and 19 controls were enrolled in this study. Blood samples were obtained just before and soon after the first administration of edaravone (30 mg) or ozagrel (40 mg). Intracellular reactive oxygen species of neutrophils were measured using 6-carboxy-2', 7'-dichlorodihydrofluorescin diacetate and a fluorescence-activated cell sorter. Superoxide from neutrophils, induced by phorbol myristate acetate (PMA), was determined by luminol-amplified chemiluminescence assay. RESULTS: Treatment with 30 mg of edaravone significantly decreased the intracellular reactive oxygen species (ROS) of neutrophils (Wilcoxon test, p=0.0001) and PMA-induced superoxide produced by neutrophils (Wilcoxon test, p=0.001). Ozagrel did not alter the intracellular ROS or superoxide production of neutrophils. CONCLUSION: Reduction of intracellular ROS and suppression of superoxide production in neutrophils provide a potential explanation for the clinical efficacy of edaravone in patients with ischemic brain attack.

Aged↗

Neurodevelopmental outcome in children with intraventricular hemorrhage.

To clarify the neurodevelopmental outcome in children with intraventricular hemorrhage, a follow-up study was performed for a consecutive group of 335 subjects in one tertiary center born between 1981 and 1999. Their mean gestation and birth weight were 28.1 weeks and 1162.2 gm, respectively. The follow-up period ranged from 3 to 20 years (mean: 7.5 years). The neurodevelopmental outcomes were normal in 188 (56.1%), cerebral palsy in 75 (22.4%), mental retardation in 34 (10.2%), and borderline intelligence in 38 (11.3%). There were statistically significant differences in the outcomes among the groups with different grades of intraventricular hemorrhage. Approximately 70% of the children with intraventricular hemorrhage grade 1 were normal, whereas only 15.4% of the children with intraventricular hemorrhage grade 4 were normal. Cerebral palsy was associated with as high as 71.2% in the patients with intraventricular hemorrhage grade 4. The overall incidence of epilepsy was 39/335 (11.6%). This study has not demonstrated clear improvement of the outcome in children with intraventricular hemorrhage between the 1980s and 1990s.

Adolescent↗

Cytokine production of CD8+ immune T cells but not of CD4+ T cells from Toxoplasma gondii-infected mice is polarized to a type 1 response following stimulation with tachyzoite-infected macrophages.

To examine whether cytokine production of CD4(+)immune T cells and CD8(+)immune T cells in Toxoplasma gondii-infected mice differ in their responses to infected cells and to soluble antigens of the parasite, we compared the production of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-10 by the immune T cell populations following in vitro stimulation with tachyzoite-infected macrophages and tachyzoite lysate antigens (TLA). Both CD4(+)and CD8(+)immune T cells produced large amounts of IFN-gamma in response to either infected macrophages or TLA, but the CD4(+)T cells produced greater amounts of the cytokine than did the CD8(+)T cells with both stimulations. Both T cell populations also produced IL-2 after stimulation with infected macrophages, whereas only CD4(+)T cells did when stimulated with TLA. CD4(+)immune T cells also produced large amounts of IL-4 and IL-10 after stimulation with infected macrophages, but CD8(+)T cells did not. These results indicate that CD4(+)immune T cells produce IFN-gamma, IL-2, IL-4, and IL-10 in response to infected macrophages, whereas CD8(+)immune T cells produce predominantly IFN-gamma and IL-2. Since IL-4 and IL-10 could suppress IFN-gamma-mediated protective mechanisms against the parasite, the production of these cytokines by CD4(+)immune T cells in response to infected cells could negatively affect their protective activity in vivo.

Animals↗

Changes in adipopnectin, leptin, and fat mass after clenbuterol treatment in horses.

INTRODUCTION: Adipose tissue plays complex role(s) in metabolic and endocrine control. To date, little work has been done in the horse regarding adipocytokines. PURPOSE: This study was conducted to determine whether therapeutic levels of chronic beta-agonist administration, exercise, or both could alter their concentrations. METHODS: A total of 23 standard-bred mares were divided into four experimental groups: clenbuterol (2.4 microg.kg(-1) bw twice daily for 8 wk) plus exercise (8 wk, 20 min.d(-1) at 50% VO2max; CLENEX; N = 6), clenbuterol only (CLEN; N = 6), exercise only (EX; N = 5), and control (CON; N = 6). Rump fat thickness was measured using B-mode ultrasound and percent body fat (%fat) was calculated. Plasma adiponectin and leptin concentrations were measured using radioimmunoassay (RIA). In the absence of purified equine adiponectin or leptin, results were expressed as human equivalents of immunoreactive adipocytokines. RESULTS: The change in plasma immunoreactive (ir)-adiponectin HE concentration was negatively correlated (r = -0.520; P = 0.01) to the change in fat mass and positively correlated (r = 0.446; P = 0.03) to the change in fat-free mass. The change in plasma ir-leptin HE concentration was positively correlated (r = 0.550; P = 0.02) to the change in fat mass and negatively correlated (r = -0.473; P < 0.05) to the change in fat-free mass. CONCLUSION: These data demonstrate that a chronic clenbuterol administration alters the concentrations of the adipocytokines adiponectin and leptin in horses. These changes may play a role in previously reported repartitioning effects of clenbuterol.

Adiponectin↗

Evaluation of Merci Retriever by experimental modeling.

The Merci Retriever is the first device for mechanical embolus removal in patients with cerebral ischemia. Use of the device was evaluated using experimental models. Three stroke model systems were created: silicone embolism model with flow system, pig embolism model, and silicone-pig tortuous artery model. The series of extraction procedures (capture, retrieval, and aspiration) was examined in the models under flow control. Coagulated blood clot was adopted as embolic material, to simulate embolic stroke of the carotid or middle cerebral arteries. Retrieval of the clot was successful in only one of six trials in the silicone model of the carotid artery, as the clot easily worked free from the helical tip. Aspiration was successful in three of the six trials. Retrieval was successful in two of four trials in the middle cerebral artery and aspiration was successful in two. Retrieval was successful in all five trials in the pig embolism model, and three of five trials in the silicone-pig tortuous artery model. The Merci Retriever does not always retain the embolism, and the helix tends to distort in acute or rough lumen. Aspiration is not always successful.

Animals↗

Two cases of ductal adenoma of the breast.

We encountered two cases of ductal adenoma of the breast. In the first case, a 32-year-old woman presented with a two-year history of a left breast lump. Previous ultrasonography had demonstrated three tumors which were thought to be most likely fibroadenoma. On excisional biopsy of the largest , intraoperative pathological examination of frozen sections was suspicious for ductal carcinoma with a differential diagnosis of intraductal papilloma or intraductal papillary carcinoma. Ductal adenoma was diagnosed after pathological examination of the permanent sections. The second case was a 64-year-old woman who presented with a hard lump in her left breast. Mammography and ultrasonography demonstrated images typical of carcinoma. Aspiration biopsy cytology (ABC) repeated twice was reported as " indeterminate". Excisional biopsy was later done. Ductal adenoma (sclerosing papilloma) with hemorrhagic infarction was diagnosed. It is noteworthy that ductal adenoma have clinical and histopathological features that should be differentiated from carcinoma, especially when the tumor is accompanied by secondary changes such as hemorrhage or infarction.

Adenoma↗