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Biomedical subjects

S Fukuda

Publications and source records attributed to S Fukuda.

At least 37 records · Page 2Linked to original sources

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen.

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.

ADAM Proteins↗

Immunoregulatory defects of V alpha 24V+ beta 11+ NKT cells in development of Wegener's granulomatosis and relapsing polychondritis.

The frequency of either CD4(-)8(-) (double negative; DN) or CD4(+) V alpha 24(+)V beta 11(+) NKT cells, the expression of CD1d and the binding of CD1d-tetramer loaded with alpha-galactosylceramide (alpha-GalCer) to NKT cells were analysed in peripheral blood mononuclear cells (PBMCs) of patients with Wegener's granulomatosis (WG), relapsing polychondritis (RP) and healthy subjects (HS). DN and CD4(+) V alpha 24(+)V beta 11(+) NKT cells as well as CD1d-alpha-GalCer tetramer-positive NKT cells, were significantly decreased in number in both WG and RP patients compared to those from HS. When cytokine profiles were analysed in these PBMCs upon stimulation with phorbol ester and calcium ionophore, CD4(+) T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4(+) NKT cells from WG patients in remission showed a Th2 bias. These findings suggest that NKT cells (especially CD4(+) NKT cells) play a regulatory role in Th1 autoimmunity in patients with WG and RP. The reduction in NKT cell counts appears to be associated with the low responsiveness to alpha-GalCer. The dysfunction of NKT cells to recognize ligands such as alpha-GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.

Aged↗

Intussusception in neonates: analysis of 14 Japanese patients.

OBJECTIVE: To clarify the clinical features and pathogenesis of intussusception in neonates. METHODS: Fourteen neonates were diagnosed with intussusception between June 1974 and January 2001. Patients were divided into two groups according to whether or not signs were present on the first day of life. The clinical features were interrelated with the pathological findings. RESULTS: All six patients in the group whose signs were present on the first day of life also had intestinal atresia or malrotation. Among patients whose signs began less than 24 h after birth, five of eight patients suffered hypoxia. Moreover, it was very difficult to establish the diagnosis of intussusception, particularly in the group of late-onset type intussusception. CONCLUSIONS: Hypoxic events may play a crucial aetiologic role in the pathogenesis of late-onset neonatal intussusception.

Female↗

High frequency of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive Clostridium difficile in a hospital in Japan and risk factors for infection.

Patients hospitalized in a hospital with a high incidence of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive (A-/B+) Clostridium difficile were retrospectively investigated to determine the clinical manifestations and risk factors for infection. Of 77 Clostridium difficile isolates obtained from 77 patients during the 1-year investigation period, 30 were A-/B+ and 47 were toxin A-positive, toxin B-positive (A+/B+). By pulsed-field gel electrophoresis analysis, 23 of the 30 A-/B+ strains were outbreak-related, suggesting nosocomial spread of a single type of bacterium, which mainly affected patients in the wards of respiratory medicine, hematology and neurology. Using regression analysis, three factors were found to be associated with infection by A-/B+ isolates: (i) exposure to antineoplastic agents ( P=0.01, odds ratio [OR]=5.1), (ii) the use of nasal feeding tubes ( P=0.008, OR=5.2), and (iii) assignment to a certain internal medicine ward ( P=0.05, OR=3.0). Between patients with Clostridium difficile-associated diarrhea caused by A-/B+ strains and those with A+/B+ strains, no statistically significant difference was found in body temperature, serum concentration of C-reactive protein, leukocyte count in whole blood, frequency of diarrhea, or type of underlying disease. These results indicate that A-/B+ strains of Clostridium difficile can cause intestinal infection in humans and they spread nosocomially in the same manner as A+/B+ strains.

Adolescent↗

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↗

Characteristics of the antihistamine effect of TAK-427, a novel imidazopyridazine derivative.

OBJECTIVE AND DESIGN: The characteristics of the antihistamine effect of the new antiallergic compound TAK-427 were investigated. MATERIALS AND METHODS: In vitro binding assay of [(3)H] pyrilamine was performed using recombinant human histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR mice or Hartley guinea pigs. Drugs were administered orally 1 h before examinations. Determinations were made of histamine-induced skin reaction, ex vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital-induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen-induced itch-scratch responses (ISRs). RESULTS: TAK-427 inhibited ligand binding to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine-induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and 0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as high selectivity for peripheral H(1) receptors as terfenadine and epinastine did, which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg, TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427 significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen-induced ISRs in guinea pigs. CONCLUSIONS: These results suggest that TAK-427 may have a long-lasting antihistamine activity with minimum sedative side effect and suppress acute phase allergic reactions.

Algorithms↗

Effect of lysed Enterococcus faecalis FK-23 (LFK) on allergen-induced peritoneal accumulation of eosinophils in mice.

BACKGROUND: The interest in anti-allergy immunoregulation by lactic acid bacteria has been growing for the last few decades. There is some evidence to suggest that lysed Enterococcus faecalis FK-23 (LFK) could relieve the clinical symptoms of pollinosis. However, the mechanism responsible for this phenomenon remains unknown. OBJECTIVE: To identify the effect of LFK, a lysozyme treated and heat-killed preparation from the lactic acid bacteria Enterococcus faecalis FK-23 strain, on allergen-induced eosinophil accumulation. METHODS: BALB/c mice were sensitized with ragweed pollen extract, and peritoneal accumulation of eosinophils was induced. A total of 60 mg (0.5 mL) LFK was orally administered to the experimental mouse every day during 21 days of the sensitization period. In addition, LFK 4 mg, 25 mg and 60 mg (each 0.5 mL) were also orally administered to a mouse of each group every day for 21 days. Saline was fed in a dose of 0.5 mL/mouse per day for the same duration as a control. RESULTS: Compared with control mice, LFK-treated mice exhibited decreased ragweed pollen allergen-induced peritoneal accumulation of eosinophils (P = 0.013), which showed a tendency to be in a dose-dependent fashion (P = 0.14). CONCLUSION: The results provide laboratory evidence of the role for LFK, a lactic acid bacteria preparation, in combating eosinophil accumulation.

Administration, Oral↗

Experimental study of blood typing in immunosuppressant-free tracheal transplantation in dogs.

BACKGROUND: A previous report has noted that tracheal allotransplantation is possible using allografts without immunosuppressants. In the present study, we investigated whether blood typing is necessary in immunosuppressant-free tracheal allotransplantation in dogs. METHODS: In group 1, the blood types of paired dogs were mismatched (n=6, three pairs), while the blood types of paired dogs were matched in group 2 (n=6, three pairs). In paired dogs, an intrathoracic 5-ring tracheal segment was exchanged. No immunosuppressants were used. RESULTS: All animals survived for more than 8 weeks. In each group, different degrees of airway stenosis were observed in four dogs. However, no stenosis was observed in the other two dogs. Histologically, no vascular rejection was detected. Ciliated columnar epithelium covered the inner surface of the implanted graft in the long-term survival cases. CONCLUSIONS: In immunosuppressant-free tracheal allotransplantation, no hyperacute rejection occurred in any recipient dog whose blood type was mismatched with the donor. Blood typing was not the key factor to successful immunosuppressant-free tracheal allotransplantation. Immunosuppressant-free tracheal allotransplantation may be possible using mismatched blood type tracheal grafts.

Animals↗

Validity of simple mucosal biopsy criteria combined with endoscopy predicting patients with ulcerative colitis ultimately requiring surgery: a multicenter study.

BACKGROUND: Recent mucosal biopsy criteria combined with endoscopy effectively differentiate patients with ulcerative colitis ultimately requiring surgery (UC-S) from those receiving medication alone (UC-M). However, the criteria were inconvenient in practical use because of the need for complicated calculations, and the validity has not been verified in other institutes where the indications for surgery may differ. The aims of this multicenter study were to propose simple criteria in which calculation can be performed by mental arithmetic and to measure their validity. METHODS: Based on the above original criteria, we constructed simple criteria in which coefficients and constant were simplified to integral numbers. The criteria consisted of the diagnostic categories, highest-risk, high-risk, unpredictable, low-risk, and lowest-risk of surgery. The validity of these proposed criteria was evaluated in 121 patients with UC-S and 186 with UC-M from 11 institutes. RESULTS: The categories of high-risk and low-risk had sensitivities exceeding 86.0% and specificities exceeding 95.2%, and the validities were maintained at high levels in most individual institutes. There was little difference in validity between the proposed and original criteria when testing using the same patients. CONCLUSIONS: Despite simplified coefficients and constant, the proposed criteria reliably predicted the eventual clinical outcome of patients with ulcerative colitis and would be helpful in determining the necessity of surgery.

Adolescent↗

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↗

Evaluation of a 24-hour bioluminescent enzyme immunoassay for the rapid detection of Salmonella in chicken carcass rinses.

A bioluminescent enzyme immunoassay (BEIA), using Salmonella-specific monoclonal antibody M183 for capture and biotinylated monoclonal antibody M183 for detection, was developed with InteLite AB streptavidin-biotinylated firefly luciferase complex as a reporter. Salmonella cultures were preenriched in buffered peptone water with shaking for 6 h at 37 degrees C and then selectively enriched in Muller-Kauffmann tetrathionate (MKTT) broth and modified semisolid Rappaport-Vassiliadis (MSRV) medium for 16 h at 42 degrees C. After enrichment, the total test time for the BEIA was 1.5 h. The analytical sensitivity of the BEIA ranged from 6.0 x 10(2) CFU/ml to 1.2 x 10(5) CFU/ml in MKTT and from 1.4 x 10(5) to 2.3 x 10(6) CFU/ml in MSRV using six Salmonella serovars prevalent in Canada. With enrichment cultures, the BEIA detected 1 CFU of Salmonella Typhimurium and Salmonella Enteritidis in 25 ml of chicken rinses. Representative strains of 10 Salmonella serovars were detected, and cross-reactivity was not observed with 25 non-Salmonella foodborne bacteria. The BEIA performance was assessed by testing 420 poultry samples, which were analyzed in parallel with the standard MSRV culture method. The BEIA detected 117 (27.88%) Salmonella-positive samples, whereas the standard MSRV culture method detected 124 (29.5%). The BEIA had a sensitivity of 64.5% and a specificity of 87.5% compared to the standard MSRV culture method. However, similar specificities and sensitivities were obtained when the standard MSRV culture method was compared to the BEIA (sensitivity = 68.4% and specificity = 85.5%). Neither method detected 100% of the Salmonella found in the samples tested, and statistical analyses indicated no significant difference between the two methods. In summary, the BEIA offers another alternative for the detection of Salmonella, with the additional advantage of providing a 24-h test for detecting Salmonella in chicken carcass rinses. The results obtained in this research indicate that tests are still needed for the isolation and detection of Salmonella that will establish the true prevalence of Salmonella in chicken samples.

Animals↗

Biopsy pathology predicts patients with ulcerative colitis subsequently requiring surgery.

BACKGROUND: The clinical course of patients with ulcerative colitis (UC) is unpredictable, and 17%-38% ultimately require surgery. We hypothesized that mucosal histology may differ between patients requiring surgery and those receiving medication alone. The aim of this study was to elucidate comprehensive criteria consisting of specific histologic features enabling the prediction of failure to medical treatment. METHODS: We studied colorectal biopsy specimens from 67 patients ultimately requiring surgery (UC-S) and 90 receiving medication alone for more than 3 years (UC-M), and conducted multiple logistic regression analysis on 70 histologic features together with endoscopic disease extent and patient age. The analysis constructed an equation finding probability of UC-S (P(UC-S)). Based on a receiver-operating characteristic curve, we selected four cut-off values of P(UC-S), and determined criteria of five categories: highest-risk, higher-risk, unpredictable, lower-risk and lowest-risk of surgery. Sensitivity and specificity of criteria were evaluated in a 2 x 5 table. RESULTS: Statistically significant features predicting UC-S were deep ulceration (X1), frequent crypt abscesses (X2), focal and segmental mononuclear cell infiltration (X3 and X4), paucity of eosinophils (X5: eosinophil infiltration) and wide extent of the disease (X6). The regression equation was as follows: logitP(UC-S) = -16.26 + 3.20X1 + 4.83X2 + 11.65X3 + 5. 10X4 - 5.59X5 + 5.53X6. Higher-risk and lower-risk showed sensitivity exceeding 91.0% and specificity exceeding 98.5% in predicting the outcome. CONCLUSIONS: Our criteria incorporating specific histologic features and endoscopic disease extent reliably predict eventual clinical outcome, and are expected to prove useful in determining the necessity of surgery.

Adult↗

New applications of intracardiac echocardiography: assessment of coronary blood flow by colour and pulsed Doppler imaging in dogs.

OBJECTIVE: To explore the application of a new 10 French intracardiac echocardiography (ICE) catheter with phased array and Doppler capable transducer for the assessment of epicardial and intramyocardial coronary blood flow. METHODS: The coronary arteries were detected by cross sectional imaging in seven closed chest dogs, and coronary blood flow visualised by colour Doppler. Blood flow velocities were recorded by pulsed Doppler at baseline for reproducibility of repeated measurements, and during hyperaemia for coronary flow reserve measurements. Comparisons were made with Doppler guide wire data obtained simultaneously. Intramyocardial coronary artery blood flow was assessed by colour flow mapping, and the blood flow velocities recorded using pulsed Doppler at baseline and during hyperaemia. RESULTS: Seven left main, six left anterior descending, seven left circumflex, and five right coronary arteries were visualised in the seven animals by cross sectional or colour Doppler imaging. Repeated measurements of coronary flow velocity showed a good correlation (mean diastolic velocity, r = 0.93, n = 22, p < 0.0001; peak diastolic velocity, r = 0.96, n = 22, p < 0.0001, respectively). Intraobserver/interobserver variability was satisfactorily low. Coronary flow reserve from ICE correlated highly with the value obtained from the Doppler guide wire (r = 0.90, n = 26, p < 0.0001). Intramyocardial coronary blood flow was identified in all seven dogs, and flow velocities were recorded at baseline and during hyperaemia in four animals. CONCLUSIONS: This new ICE catheter provides high quality diagnostic resolution. It is useful for coronary blood flow assessment.

Animals↗

Changes in transmural distribution of myocardial perfusion assessed by quantitative intravenous myocardial contrast echocardiography in humans.

OBJECTIVE: To clarify whether changes in transmural distribution of myocardial perfusion under significant coronary artery stenosis can be assessed by quantitative intravenous myocardial contrast echocardiography (MCE) in humans. METHODS: 31 patients underwent dipyridamole stress MCE and quantitative coronary angiography. Intravenous MCE was performed by continuous infusion of Levovist. Images were obtained from the apical four chamber view with alternating pulsing intervals both at rest and after dipyridamole infusion. Images were analysed offline by placing regions of interest over both endocardial and epicardial sides of the mid-septum. The background subtracted intensity versus pulsing interval plots were fitted to an exponential function, y = A (1 - e(-betat)), where A is plateau level and beta is rate of rise. RESULTS: Of the 31 patients, 16 had significant stenosis (> 70%) in the left anterior descending artery (group A) and 15 did not (group B). At rest, there were no differences in the A endocardial to epicardial ratio (A-EER) and beta-EER between the two groups (mean (SD) 1.2 (0.6) v 1.2 (0.8) and 1.2 (0.7) v 1.1 (0.6), respectively, NS). During hyperaemia, beta-EER in group A was significantly lower than that in group B (1.0 (0.5) v 1.4 (0.5), p < 0.05) and A-EER did not differ between the two groups (1.0 (0.5) v 1.2 (0.4), NS). CONCLUSIONS: Changes in transmural distribution of myocardial perfusion under significant coronary artery stenosis can be assessed by quantitative intravenous MCE in humans.

Contrast Media↗

Evaluation of peripheral nerve regeneration across an 80-mm gap using a polyglycolic acid (PGA)--collagen nerve conduit filled with laminin-soaked collagen sponge in dogs.

We evaluated peripheral nerve regeneration using a novel artificial nerve conduit. The conduit was made of a polyglycolic acid(PGA) - collagen tube filled with laminin- soaked collagen sponge. We implanted this nerve conduit across an 80mm gap in the peroneal nerve of dogs. Histological observation 12 months after implantation showed numerous unmyelinated and myelinated nerve fibershad regenerated beyond the gap. Neurofilaments were widely observed immunohistochemically in the regenerated nerve segments. These findings indicated that newly regenerated axons had extended across the gap and connected into the distal nerve segments. Compound muscle action potentials(CMAPs) and somatosensory evoked potentials (SEPs) were recorded in all dogs. At 12 months, the CMAPs indicated complete recovery, while the SEPs showed incomplete but substantial recovery. Walking patterns had returned to near-normal 12 months after implantation. Use of this nerve conduit can lead to peripheral nerve elongation and favorable functional recovery across a wider nerve gap.

Absorbable Implants↗