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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 37 records · Page 2Linked to original sources

Relation between C reactive protein concentrations and coronary microvascular endothelial function.

OBJECTIVE: To determine how C reactive protein (CRP), a sensitive marker of inflammation, is related to coronary endothelial function. DESIGN: Changes in quantitative coronary angiographic findings and Doppler flow velocity measurements in response to locally infused acetylcholine were assessed. SETTING: Tertiary cardiology centre. PATIENTS: 46 patients with angiographically normal coronary arteries were divided into groups with normal (< or = 3 mg/l) or increased (> 3 mg/l) CRP concentrations. INTERVENTIONS: Acetylcholine (3 and 30 microg/min) was infused into the left coronary ostium for two minutes. MAIN OUTCOME MEASURES: Percentage change in diameter of epicardial coronary arteries and coronary blood flow (CBF) in response to acetylcholine; and correlations between these parameters and serum CRP concentrations. RESULTS: 15 patients had increased CRP concentrations. The change in coronary artery diameter induced by acetylcholine infusion was similar between the groups but the increase in CBF induced by acetylcholine was smaller in patients with increased CRP concentrations (54.9% v 139.4% with acetylcholine 30 microg/min, p = 0.0030). Multivariate analysis identified increased CRP concentration as independently associated with attenuated CBF response to acetylcholine at 30 microg/min (p = 0.0078, R2 = 0.434). CONCLUSIONS: These findings suggest that inflammation appears to be associated with impaired coronary endothelial function in resistance but not conduit vessels. The data suggest a close relation between chronic vascular inflammation and endothelial dysfunction in atherosclerosis.

Acetylcholine↗

Immunokinetics in severe pneumonia due to influenza virus and bacteria coinfection in mice.

Coinfections of bacteria and influenza are a major cause of excessive mortality during influenza epidemics. However, the mechanism of the synergy between influenza virus and bacteria are poorly understood. In this study, mice were inoculated with influenza virus, followed 2 days later by inoculation with Streptococcus pneumoniae. The kinetics of viral titres, bacterial numbers and the immune response (cytokine and chemokine production) were also analysed. Short-term survival correlated with pathological changes in the lungs of infected mice. Influenza virus or S. pneumoniae infection alone induced moderate pneumonia; however, severe bronchopneumonia with massive haemorrhage in coinfected mice, which caused death of these mice approximately 2 days after inoculation with S. pneumoniae, was noted. Intrapulmonary levels of inflammatory cytokines/chemokines, type-1 T-helper cell cytokines and Toll-like receptors, and the related mitogen-activated protein kinase signalling molecules (phosphorylated extracellular signal-regulated kinase -1 and - 2, p38 and c-Jun N-terminal kinase), were increased in coinfected mice. These results suggest that immune mediators, including cytokines and chemokines, through Toll-like receptors/mitogen-activated protein kinase pathways, play important roles in the pathology of coinfection caused by influenza virus and Streptococcus pneumoniae.

Animals↗

Information gain in an optical bistable system by stochastic resonance.

We have shown an experimental demonstration of information gain due to the stochastic resonance in an optical bistable system, that is, information hidden in the input wave form appears in the output of a nonlinear system when the input noise amplitude is adequate. The optical bistable system is a hybrid type comprising a LiNbO3 crystal with an electric feedback loop, and the input of the system is the sum of a binary bit series and a Gaussian colored noise. The information gain is proved to be prominent when the noise cutoff frequency is larger than the bit rate.

Journal Article↗

Search for nu(e) from the sun at Super-Kamiokande-I.

We present the results of a search for low energy nu(e) from the Sun using 1496 days of data from Super-Kamiokande-I. We observe no significant excess of events and set an upper limit for the conversion probability to nu(e) of the 8B solar neutrino. This conversion limit is 0.8% (90% C.L.) of the standard solar model's neutrino flux for total energy=8-20 MeV. We also set a flux limit for monochromatic nu(e) for E(nu(e))=10-17 MeV.

Journal Article↗

Search for supernova relic neutrinos at Super-Kamiokande.

A search for the relic neutrinos from all past core-collapse supernovae was conducted using 1496 days of data from the Super-Kamiokande detector. This analysis looked for electron-type antineutrinos that had produced a positron with an energy greater than 18 MeV. In the absence of a signal, 90% C.L. upper limits on the total flux were set for several theoretical models; these limits ranged from 20 to 130 macro nu(e) cm(-2) s(-1). Additionally, an upper bound of 1.2 macro nu(e) cm(-2) s(-1) was set for the supernova relic neutrino flux in the energy region E(nu)>19.3 MeV.

Journal Article↗

Indications of neutrino oscillation in a 250 km long-baseline experiment.

The K2K experiment observes indications of neutrino oscillation: a reduction of nu(mu) flux together with a distortion of the energy spectrum. Fifty-six beam neutrino events are observed in Super-Kamiokande (SK), 250 km from the neutrino production point, with an expectation of 80.1(+6.2)(-5.4). Twenty-nine one ring mu-like events are used to reconstruct the neutrino energy spectrum, which is better matched to the expected spectrum with neutrino oscillation than without. The probability that the observed flux at SK is explained by statistical fluctuation without neutrino oscillation is less than 1%.

Journal Article↗

Intravitreal injections of neurotrophic factors and forskolin enhance survival and axonal regeneration of axotomized beta ganglion cells in cat retina.

Some retinal ganglion cells in adult cats survive axotomy for two months and regenerate their axons when a peripheral nerve is transplanted to the transected optic nerve. However, regenerated retinal ganglion cells were fewer than 4% of the total retinal ganglion cell population in the intact retina. The present study examined the effects of intravitreal injections of neurotrophic factors (brain-derived neurotrophic factor, ciliary neurotrophic factor, basic fibroblast growth factor, glial cell-derived neurotrophic factor, neurotrophin 4), first on the survival of axotomized cat retinal ganglion cells within 2 weeks, and then on axonal regeneration of the retinal ganglion cells for 2 months after peripheral nerve transplantation. We tested first enhancement of the survival by one of the factors, and then one or two of them supplemented with forskolin, which increases intracellular cAMP. Single injections of 0.5 microg or 1 microg brain-derived neurotrophic factor, 1 microg ciliary neurotrophic factor, or 1 microg glial cell-derived neurotrophic factor significantly increased total numbers of surviving retinal ganglion cells; 1.6-1.8 times those in control retinas. Identification of retinal ganglion cell types with Lucifer Yellow injections revealed that the increase of surviving beta cells was most conspicuous: 2.5-fold (brain-derived neurotrophic factor) to 3.6-fold (ciliary neurotrophic factor). A combined injection of 1 microg brain-derived neurotrophic factor, 1 microg ciliary neurotrophic factor, and 0.1 mg forskolin resulted in a 4.7-fold increase of surviving beta cells, i.e. 50% survival on day 14. On the axonal regeneration by peripheral nerve transplantation, a combined injection of brain-derived neurotrophic factor, ciliary neurotrophic factor, and forskolin resulted in a 3.4-fold increase of beta cells with regenerated axons. The increase of regenerated beta cells was mainly due to the enhancing effect of neurotrophic factors on their survival, and possibly to a change of retinal ganglion cell properties by cAMP to facilitate their axonal regeneration.

Animals↗

Isolation of peptides useful for differential diagnosis of Crohn's disease and ulcerative colitis.

BACKGROUND: Phage displayed random peptide technology has been utilised to identify binding epitopes of antibodies or receptor ligands. AIM: To isolates peptides from a phage library which are specifically recognised by antibodies in serum from patients with Crohn's disease (CD). METHODS: A phage displayed random peptide library composed of nine amino acids was established and sequentially screened using serum immunogloblin G obtained from CD patients. RESULTS: Five different CD specific peptides were isolated from the phage library. No homology in amino acid sequences was observed among four (CDP-1, -3 to -5) of the five peptides exhibiting different binding characteristics with each CD patient's serum. In contrast, two peptides (CDP-1 and -2) had similar amino acid sequences and similar binding characteristics. Four multiple antigenic peptides (MAP, CDP-1, -3 to -5) were synthesised, and an enzyme linked immunosorbent assay (ELISA) using the four peptides was developed to detect serum antibodies against them. Fifty two of 92 CD patients (56.5%) were detected by ELISA, none of 20 ulcerative colitis (UC) patients, only one of 25 duodenal ulcer patients, and only three of 48 healthy subjects. CONCLUSIONS: ELISA using the four peptides isolated in this study may be useful for the differential diagnosis of CD and UC.

Amino Acid Sequence↗

Helicobacter pylori water soluble surface proteins prime human neutrophils for enhanced production of reactive oxygen species and stimulate chemokine production.

BACKGROUNDS/AIMS: Chronic gastritis induced by Helicobacter pylori is characterised by considerable neutrophil infiltration into the gastric mucosa without mucosal invasion of bacteria. Bacteria have different characteristics with respect to their ability to stimulate human neutrophils to produce reactive oxygen species and chemokines. The aim of this study was to examine the effects of H pylori water extracts on the oxidative burst and chemokine production of human neutrophils. METHODS: Helicobacter pylori cells were extracted by harvesting into distilled water and centrifugation. Neutrophils were incubated with H pylori water extracts and the production of reactive oxygen species was measured using luminol dependent chemiluminescence (LmCL). In addition, the concentrations of chemokines (interleukin 8 (IL-8), macrophage inflammatory protein 1-alpha (MIP1-alpha), and MIP1-beta) were measured by enzyme linked immunosorbent assay. Neutrophils were also stimulated by opsonised zymosan (OZ) after preincubation with H pylori water extracts. RESULTS: Helicobacter pylori water extracts alone induced only a weak oxidative burst but preincubation of neutrophils with water extracts dose dependently enhanced the LmCL response stimulated by OZ. Helicobacter pylori water extracts also stimulated neutrophil IL-8 production, although MIP-1beta production was only stimulated weakly, and MIP-1alpha was not stimulated at all. CONCLUSIONS: Helicobacter pylori products in water extracts may have a role in the activation and migration of neutrophils, which results in enhanced oxidative damage to gastric mucosa. These findings may explain the pathology of H pylori induced gastritis, in which there is little invasion of bacteria into the gastric mucosa.

Bacterial Outer Membrane Proteins↗

Intestinal goblet cell autoantibody associated enteropathy.

This report describes a case of refractory enteropathy with circulating intestinal goblet cell autoantibodies (IGA). A 19 year old man with hyperthyroidism had suffered from protracted diarrhoea for nearly 10 years. Histological examination showed evidence of collagenous enterocolitis. The diarrhoea did not improve despite fasting under total parenteral nutrition. An immunofluorescence assay demonstrated IGA without anti-enterocyte autoantibodies, the hallmark of autoimmune enteropathy, although other criteria were fulfilled. None of 109 controls, including 55 cases of inflammatory bowel disease and one of lymphocytic colitis, had IGA. This case is considered to be a variant of autoimmune enteropathy, and might be a distinct entity.

Adult↗

Chromosomal instability and human hepatocarcinogenesis.

Recently, many studies have identified losses and gains of several chromosomal loci in human hepatocellular carcinoma (HCC) with fine microsatellite analysis and comparative genomic hybridization. Although distribution of aberrant chromosomal arms differs among HCCs, loss of 1p, 4q, 6q, 8p, 9p, 10q, 13q, 16q and 17p, and gain of 1q, 6p, 8q, 17q and 20q have been recurrently reported, and loss of 4q and 16q seems to occur preferentially in hepatitis B virus-related HCCs. Accumulation of these aberrant chromosomal regions is associated with tumor progression, and some chromosomal aberrations, such as loss of 1p, are frequently identified in well-differentiated HCCs and also detected even in dysplastic nodule and cirrhotic nodule. This evidence suggests that chromosomal instability (CIN) emerges at an early stage during hepatocarcinogenesis and is successively inherent to tumor cells, resulting in acquisition of malignant phenotype. The molecular basis of CIN is beginning to be explored; however, several mechanisms may be involved for CIN of HCC.

Allelic Imbalance↗

Effect of Bcl-2 overexpression on establishment of ipsilateral retinocollicular projection in mice.

During perinatal development in rodents, ipsilateral retinofugal projection spreading over the superior colliculus is eventually restricted to the rostromedial region. Since this restriction is accompanied by the apoptotic death of more than half of the retinal ganglion cells (RGCs), cell death is believed to play a major role in the restriction of transient ipsilateral projection from the retina to the superior colliculus. To determine the role of RGC death in the establishment of ipsilateral retinofugal projection, we examined the projection pattern in the superior colliculus and the dorsal lateral geniculate nucleus of transgenic mice overexpressing the human bcl-2 gene, which protects against cell death in the CNS. Retrograde labeling of RGCs showed that the number of ipsilaterally projecting RGCs in adult transgenic mice was approximately twice that in adult wild-type mice, indicating that the naturally occurring death of RGCs was prevented in these mutant mice. However, anterograde labeling of ipsilateral retinofugal pathways revealed that the innervation of retinogeniculate and retinocollicular projections was as restricted in transgenic mice as in wild-type mice. From these results we suggest that restriction of ipsilateral retinofugal projection during development is due to retraction or elimination of excessive terminals rather than to naturally occurring RGC death.

Animals↗

Cell death and proliferation in Nd-YAG laser, electrocautery, and scalpel wounds on mice skin.

The purpose of this study is to compare cell death and proliferation in laser, electrocautery and scalpel wounds on the mice epidermis. Wounds were examined by transmission electron microscopy, the detection of free 3'-OH DNA ends and immunohistochemistry of proliferating cell nuclear antigen (PCNA), inducible nitric oxide synthase (iNOS), keratinocyte growth factor (KGF) and keratinocyte growth factor receptor (KGFR). Reepithelization was first observed 5 days after scalpel and laser incisions and 7 days after electrocautery incision. Ultrastructurally, keratinocytes in both electrocautery and laser wounds showed similar post-apoptotic necrotic changes. Interestingly, dividing cells were often observed 3 days after laser incision. Apoptotic index in electrocautery wounds was higher than in laser wounds, although there was no significant difference in the PCNA expression level between them. The expression of iNOS, KGF and KGFR in laser wounds was more intense than in electrocautery wounds. In scalpel wounds, keratinocytes did not show significant changes in morphology or of markers of cell death and proliferation during the observation period. Therefore, the increase in the number of dividing cells and in the expression level of iNOS, KGF and KGFR may induce earlier and thicker reepithelization in laser wounds than in electrocautery and scalpel wounds.

Animals↗

Fukuyama-type congenital muscular dystrophy: a case report in the Japanese population living in Brazil.

INTRODUCTION: We present herein clinical, histological and magnetic resonance imaging (MRI) findings in a patient with Fukuyama-type congenital muscular dystrophy (FCMD). He is the first case report in the Japanese population living in Brazil. CASE REPORT: The child presented with neonatal hypotonia, delayed motor abilities and speech, seizures, cerebral and cerebellar gyrus abnormalities with signal intensity change in the white matter by MRI, high serum level of creatinephosphokinase (CK), and dystrophic skeletal muscle with normal merosin, alpha-sarcoglycan and dystrophin expression. The fukutin gene study showed one founder 3-kb retrotransposal insertion in the 3'-non-coding region, and in the other allele no mutation was detected after screening all exons and flanking introns by sequencing. DISCUSSION: This case report emphasizes the importance to consider FCMD in Japanese people living in other countries.

Brain↗

Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease.

BACKGROUND: The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori. Recent studies have shown that the eradication of H. pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long-term outcome. AIMS: To evaluate the relapse rate of peptic ulcer in the long-term follow-up of patients after H. pylori eradication therapy. PATIENTS AND METHODS: Patients infected with H. pylori (445; 88 duodenal ulcer, 357 gastric ulcer) were randomly divided into three groups. In group A, patients received 'conventional treatment' including acid decreasing therapy with a histamine H2-receptor antagonist or proton pump inhibitor (PPI). In group B, patients received 'dual therapy' including one antibiotic plus acid-decreasing therapy. In group C, patients received 'triple therapy' with PPI plus amoxicillin and clarithromycin. Eradication of H. pylori infection was assessed by histology of biopsy specimens from both the antrum and body corpus at 4 weeks, and 6 and 12 months after stopping therapy. Endoscopy was performed at intervals of 6 months for 5 years. RESULTS: Intention-to-treat eradication rates for the duodenal ulcer patients were 0% for group A, 46% for group B and 80% for group C; eradication rates for the gastric ulcer patients were 0%, 33% and 83% respectively. No recurrence was noted in the duodenal ulcer patients and only 4% of gastric ulcers recurred after successful eradication during follow-up for 5 years. In contrast, in patients with persistent H. pylori infection all DU and 92% of gastric ulcers recurred. CONCLUSION: Eradication of H. pylori infection changes the natural course of peptic ulcer.

Anti-Bacterial Agents↗

Involvement of cAMP-response element binding protein in corticotropin-releasing factor (CRF)-induced down-regulation of CRF receptor 1 gene expression in rat anterior pituitary cells.

Corticotropin-releasing factor (CRF) is a major secretagogue of adrenocorticotopic hormone from the anterior pituitary and a key activator of the hypothalamic-pituitary-adrenal axis. We previously reported that CRF down-regulates expression of the CRF type-1 receptor (CRF-R1) mRNA in cultured rat anterior pituitary cells. The present study was conducted to clarify the signal transduction systems involved in CRF-induced down-regulation of CRF-R1 gene expression in the anterior pituitary. Northern blot analysis revealed that, under serum-free conditions, 10 nM CRF decreased CRF-R1 mRNA levels in cultured rat anterior pituitary cells as we reported previously. Treatment with 5 mM 8-Br-cAMP reduced CRF-R1 mRNA levels within 2 h. The mRNA level fell to 37+/-3% of the basal level at 2 h and remained low for 16 h after treatment. This CRF-induced reduction of CRF-R1 mRNA expression was inhibited completely by pretreatment with protein kinase A (PKA) inhibitor (1 microM H-89). Further examination revealed that after pretreatment with 10 microM of antisense oligodeoxynucleotide for cyclic AMP-response element binding protein (CREB), the CRF-induced inhibition of CRF-R1 mRNA was partially decreased to 79+/-4% of the control level 2 h after administration of CRF. These findings indicate that CRF may down-regulate CRF-R1 mRNA expression via a cAMP-PKA-mediated mechanism in rat anterior pituitary cells, and that CREB may mediate at least a portion of this inhibitory effect.

8-Bromo Cyclic Adenosine Monophosphate↗

Thermoluminescence in fluorapatite doped with Eu2O3 and PbO.

Thermoluminescence (TL) of fluorapatite Ca5(PO4)3F doped with Eu2O3 has been investigated for UV and X ray irradiation. Two TL glow peaks for the Eu2O3 doped sample appeared in the temperature regions about (1) 353 to 380 K and (2) 508 to 510 K, when heated at rate of 20 K.min(-1) after UV or X ray irradiation at room temperature. It has been found that the peak 2 (508 to 510 K) intensity of the samples doubly doped with Eu2O3 and PbO became strong compared with that doped with only Eu or Pb ions. From the TL spectra for the Ca5(PO4)3F doped activators, it is concluded that the TL of Eu2+ ions is sensitised by the existence of Pb2+ ions. On the other hand, the TL of Eu3+ ions is not intensified by addition of PbO. The TL emission may be due to the recombination reaction: Eu3+ + e-->Eu2+*-->Eu2+ + hv. EU2+ + hole --> Eu3+* --> Eu3+ + hv. The 510 K TL peak may be also being suitable for use as a dosemeter.

Apatites↗