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Biomedical subjects

Y Fukushima

Publications and source records attributed to Y Fukushima.

At least 19 recordsLinked to original sources

The relation between spike-timing dependent plasticity and Ca2+ dynamics in the hippocampal CA1 network.

In our previous study, spike timing dependent synaptic plasticity (STDP) was investigated in the CA1 area of rat hippocampal slices using optical imaging. It was revealed that the profiles of STDP could be classified into two types depending upon layer specific location along the dendrite. The first was characterized by a symmetric time window observed in the proximal region of the stratum radiatum (SR), and the second by an asymmetric time window in the distal region of the SR. Our methods involved the bath-application of bicuculline (GABA(A) receptor antagonist) to hippocampal slices, which revealed that GABAergic interneuron projections were responsible for the symmetry of a time window. In this study, the intracellular Ca2+ increase of hippocampal CA1 neurons, induced by the protocol of timing between pre- and post-synaptic excitation (i.e. STDP protocol), was measured spatially by using optical imaging to investigate how the triggering of STDP is dependent on intracellular calcium concentration. We found that the magnitude of STDP was closely related to the rate of Ca2+ increase ("velocity") of calcium transient during application of induction stimuli. Location dependency was also analyzed in terms of Ca2+ influx. Furthermore, it was shown that decay time constant of Ca2+ dynamics during the application of STDP-inducing stimuli was also significantly correlated with STDP.

Action Potentials↗

Respiratory response to endotoxin and dust predicts evidence of inflammatory response in volunteers in a swine barn.

BACKGROUND: It has been shown that exposure in intense exposure in swine barn facilities is associated with increased respiratory symptoms and reduction in pulmonary functions. This study investigated if systemic response could be predicted by FEV(1) response following swine barn exposure. METHODS: Naïve males were tested at baseline, low and high endotoxin and dust levels. Subjects were classified as "more responsive" (n = 9) or "less responsive" (n = 11) based on FEV(1) reduction following high endotoxin exposure. Health measures included pulmonary function testing, blood samples and nasal lavage. Environmental samples were collected from the barn. RESULTS: White blood cells and blood lymphocytes at low exposure were significantly greater in those who were "more responsive" compared to those who were "less responsive". There was a significant increase in blood lymphocytes, serum IL6, total nasal lavage cells and nasal IL8 at high exposure among "more responsive" subjects compared to "less responsive" subjects. CONCLUSIONS: Respiratory response to high-level endotoxin and dust exposure predicts evidence of inflammatory response throughout a range of endotoxin and dust exposures.

Adolescent↗

Serum concentrations of resistin-like molecules beta and gamma are elevated in high-fat-fed and obese db/db mice, with increased production in the intestinal tract and bone marrow.

AIMS/HYPOTHESIS: Resistin and the resistin-like molecules (RELMs) comprise a novel class of cysteine-rich proteins. Among the RELMs, RELMbeta and RELMgamma are produced in non-adipocyte tissues, but the regulation of their expression and their physiological roles are largely unknown. We investigated in mice the tissue distribution and dimer formation of RELMbeta and RELMgamma and then examined whether their serum concentrations and tissue expression levels are related to insulin resistance. METHODS: Specific antibodies against RELMbeta and RELMgamma were generated. Dimer formation was examined using COS cells and the colon. RELMbeta and RELMgamma tissue localisation and expression levels were analysed by an RNase protection assay, immunoblotting and immunohistochemical study. Serum concentrations in high-fat-fed and db/db mice were also measured using the specific antibodies. RESULTS: The intestinal tract produces RELMbeta and RELMgamma, and colonic epithelial cells in particular express both RELMbeta and RELMgamma. In addition, RELMbeta and RELMgamma were shown to form a homodimer and a heterodimer with each other, in an overexpression system using cultured cells, and in mouse colon and serum. Serum RELMbeta and RELMgamma levels in high-fat-fed mice were markedly higher than those in mice fed normal chow. Serum RELMbeta and RELMgamma concentrations were also clearly higher in db/db mice than in lean littermates. Tissue expression levels revealed that elevated serum concentrations of RELMbeta and RELMgamma are attributable to increased production in the colon and bone marrow. CONCLUSIONS/INTERPRETATION: RELMbeta and RELMgamma form homo/heterodimers, which are secreted into the circulation. Serum concentrations of RELMbeta and RELMgamma may be a novel intestinal-tract-mediating regulator of insulin sensitivity, possibly involved in insulin resistance induced by obesity and a high-fat diet.

Animals↗

"Ring syndrome" involving chromosome 2 confirmed by FISH analysis using chromosome-specific subtelomeric probes.

"Ring syndrome" is described as those cases with complete ring chromosomes showing, independently of the chromosome involved, severe growth failure, minor dysmorphic features, and mild-to-moderate mental retardation, without major malformations. We present a girl with ring 2 chromosome, exhibiting severe growth failure, minor dysmorphic features, spontaneously closed ventricular septum defect, and normal development. G-banding chromosome analysis and fluorescence in situ hybridization (FISH) analysis using chromosome-specific subtelomeric probes (2ptel, 2qtel) demonstrated the major karyotype as 46,XX,r(2)(p25.3q37.3).ish r(2)(2ptel+,2qtel+). We review the cases with "ring syndrome" confirmed by FISH using chromosome-specific subtelomeric probes, suggesting that this method might be useful to predict developmental prognosis in a case with an apparently complete ring chromosome.

Chromosome Banding↗

[Coronary artery bypass graftingin a patient with aortitis syndrome; report of a case].

We present a case of surgical treatment for a coronary lesion due to aortitis syndrome. A 41-year-old woman, suffering from aortitis syndrome and under prednisolone (PSL) therapy, underwent coronary artery bypass grafting (CABG). Surgical treatment was performed according to the aortic no-touch technique, but the patient showed a poor cardiac performance 5 days after the operation. This accident was resolved by increasing the PSL dose. Aortitis syndrome treated with PSL needs careful perioperative management besides an operative procedure.

Adult↗

[Acute left ventricular rupture and cardiac tamponade caused by blunt trauma; report of a case].

It is difficult to save patients with acute left ventricular rupture and cardiac tamponade caused by blunt trauma. A 67-year-old man hospitalized due to sustained multiple blunt trauma. The systolic blood pressure was 40 mmHg. Chest computed tomography (CT) and ultrasonic echocardiography revealed cardiac tamponade. Abdominal CT indicated left renal contusion. Pericardial drainage via the subxiphoid approach drew about 1,000 ml of blood from the pericardial sac, which only transiently increased blood pressure. Median sternotomy and subsequent pericardiotomy revealed pulsatile bleeding jet through a laceration of about 2.0 cm long in the left ventricle near the first diagonal branch. After complete digital compression, the portion was covered by a biological tissue adhesive/sealant sheet (TachoComb), which completely suppressed bleeding. The postoperative course was uneventful. He was discharged from the hospital on the 20th day after the operation.

Acute Disease↗

Oxidative stress induces insulin resistance by activating the nuclear factor-kappa B pathway and disrupting normal subcellular distribution of phosphatidylinositol 3-kinase.

AIMS/HYPOTHESIS: Oxidative stress is associated with diabetes, hypertension and atherosclerosis. Insulin resistance is implicated in the development of these disorders. We tested the hypothesis that oxidative stress induces insulin resistance in rats, and endeavoured to identify mechanisms linking the two. METHODS: Buthionine sulfoximine (BSO), an inhibitor of glutathione synthase, was administered to Sprague-Dawley rats and 3T3-L1 adipocytes. Glucose metabolism and insulin signalling both in vivo and in 3T3-L1 adipocytes were examined. In 3T3-L1 adipocytes, the effects of overexpression of a dominant negative mutant of inhibitory kappa B (I kappa B), one role of which is to block oxidative-stress-induced nuclear factor (NF)-kappa B activation, were investigated. RESULTS: In rats given BSO for 2 weeks, the plasma lipid hydroperoxide level doubled, indicating increased oxidative stress. A hyperinsulinaemic-euglycaemic clamp study and a glucose transport assay using isolated muscle and adipocytes revealed insulin resistance in BSO-treated rats. BSO treatment also impaired insulin-induced glucose uptake and GLUT4 translocation in 3T3-L1 adipocytes. In BSO-treated rat muscle, adipose tissue and 3T3-L1 adipocytes, insulin-induced IRS-1 phosphorylation in the low-density microsome (LDM) fraction was specifically decreased, while that in whole cell lysates was not altered, and subsequent translocation of phosphatidylinositol (PI) 3-kinase from the cytosol and the LDM fraction was disrupted. BSO-induced impairments of insulin action and insulin signalling were reversed by overexpressing the dominant negative mutant of I kappa B, thereby suppressing NF-kappa B activation. CONCLUSIONS/INTERPRETATION: Oxidative stress induces insulin resistance by impairing IRS-1 phosphorylation and PI 3-kinase activation in the LDM fraction, and NF-kappa B activation is likely to be involved in this process.

3T3 Cells↗

[Clinical outcome of the coronary arterial bypass graft with inferior epigastric artery as a composite graft].

Based on a good long-patency of the internal thoracic arteries (ITA) in coronary arterial bypass graft (CABG), the postoperative early patency of the inferior epigastric artery (IEA) was evaluated by means of the proximal anastomosed types as a composite graft. Among patients performed with CABG during October in 1998 to June, 2000, 39 cases with the IEA composite graft were studied for this clinical outcome (31 males and 8 females, the averaged age was 66.4 +/- 8.0 year old). The preoperative diagnosis were done as acute myocardial infarction (4), old myocardial infarction with angina pectoris (8), effort angina (12), and unstable angina (15). The coronary disease was left main trunk disease (8), 3 vessels (22), and 2 vessels (9). The operation was performed with cold blood-cardioplegia (20 degrees C, blood-GIK liquor used) on cardiopulmonary bypass with a single atrial and aortic cannulation. The averaged extracorporeal circulation time and the aortic clamping one were done for 169 and 131 min, respectively. The bypass number was double (n = 5), triple (n = 10), quadruple (n = 16), and quintuple (n = 8). Total bypass number was 150 (the averaged bypass number was 3.7 +/- 0.9), and total anastomosal number was 145. The postoperative early-patency of IEA was 94.9% (37/39). The proximal sites of IEA were anastomozed to ITA with I-shaped end-to-end (n = 15), to ITA with Y-shaped end-to-side (n = 5), and to SVG with Y-shaped end-to-side (n = 19). Compared with the postoperative early-patency of I-shaped anastomosis to ITA and that of Y-shaped one to ITA or SVG, there was no significance among these cases (100%, 15/15 versus 91.7%, 22/24, p = 0.6738), however, that of Y-shaped one to ITA was significantly better than that of Y-shaped one to SVG (60%, 3/5 versus 100%, 19/19, p = 0.0488). It should be available for spreading of the anastomotic objective vessels that the IEA as a composite graft was used with the proximal site anastomozed to ITA by I-shaped end-to-end and with to SVG by Y-shaped end-to-side, which clinical outcome would sufficiently benefit to the patients.

Aged↗

[Study of surgical treatment with omental flap transposition for chronic empyema].

It is difficult to determine what kind of appropriate operations should be applied for which phase of chronic empyema would be administered, especially for a surgical management. We report that the postoperative outcomes of the treatment should be recommended for chronic empyema with the aid of omental flap transposition. Seven cases of chronic empyema (the averaged age was 66.1 +/- 7.5, 6 males and 1 female) in our hospital were operated during from June 1993 to January 2001. The disease-carrying time was 3 to 16 months and the inflammation findings at the admission were positive in all cases. The cause of chronic empyema was pneumonia (n = 3), plombage for tuberculosis (n = 2), and postlobectomy empyema (n = 2). As the first-stage of treatment for empyema cavity, intrathoracic tube drainage and lavage were performed for all cases. The operative procedures were described as below; one-stage operation with both thoracostomy and omental flap transposition was performed after the first-stage treatment (n = 2), simple thoracostomy (n = 1), and two-stage operation with thoracotomy and omental flap transposition (n = 4). Three of the 4 cases with two-stage operation could be completely treated for 1 month interval. However, the rest one case had not been able to be radically cured, which empyema had been extensively turned for the worse for one month after the two-stage operation. Thoracostomy had been redone, and it took 8 months to be cured. All cases could be finally recovered and discharged. On the priority of treatment for chronic empyema, at first, both thoracic tube drainage and thoracostomy should be performed as a first-stage operation, and if they could not be effective, after the combined inflammation was settled down, then the omental flap transposition should be considered as a two-stage operation.

Aged↗

Effects of rabeprazole, lansoprazole and omeprazole on intragastric pH in CYP2C19 extensive metabolizers.

AIM: To investigate the inhibitory effects on gastric acid secretion of three proton pump inhibitors, omeprazole, lansoprazole and rabeprazole, using a three-way crossover design in healthy Helicobacter pylori-negative,S-mephenytoin 4'-hydroxylase (CYP2C19) homo- and hetero-extensive metabolizers. METHODS: Eight healthy Japanese male volunteers were enrolled. After the administration of rabeprazole (10 mg/day), lansoprazole (30 mg/day) or omeprazole (20 mg/day), intragastric pH monitoring was commenced from 24 h before the first proton pump inhibitor dose, and continued for days 1-3 after proton pump inhibitor administration. The pH electrode was used for 48 h and changed just before pH monitoring on day 2. RESULTS: For the administration of 10 mg/day rabeprazole, the mean ratios of the 24-h pH > or = 3 holding time were 5.7 +/- 1.1%,13.6 +/- 2.2%, 35.3 +/- 2.7% and 62.8 +/- 3.1% for the pre-treatment day and days 1, 2 and 3, respectively. The same ratios for lansoprazole (30 mg/day) were 5.7 +/- 0.7%, 7.4 +/- 1.5%, 13.6 +/- 3.4% and 26.6 +/- 4.9%; the same ratios for 20 mg/day omeprazole were 5.9 +/- 0.9%, 6.1 +/- 1.2%, 11.4 +/- 2.8% and 16.4 +/- 4.6%. The mean ratio of the 24-h pH > or = 3 holding time of days 1-3 increased significantly compared to the pre-treatment day (P < 0.01) with the administration of rabeprazole and lansoprazole. The magnitude of inhibition of gastric acid secretion after rabeprazole administration was stronger than that after lansoprazole. A significant elevation of the mean ratio of the 24-h pH > or = 3 holding time was demonstrated on days 2 and 3 with omeprazole (P < 0.01). CONCLUSIONS: In H. pylori-negative CYP2C19 extensive metabolizers, rabeprazole (10 mg/day) shows a faster onset of rising intragastric pH and a stronger inhibition of gastric acid secretion than do lansoprazole (30 mg/day) or omeprazole (20 mg/day).

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effects of N-alpha-methyl-histamine on human H(2) receptors expressed in CHO cells.

BACKGROUND: Production of N-alpha-methyl-histamine (NAMH), a histamine H(3) receptor (H3R) agonist, is reportedly promoted in Helicobacter pylori infected human gastric mucosa. NAMH was suggested to act directly on histamine H(2) receptors (H2Rs) in animals to stimulate acid secretion and to be a H2R agonist. As H2Rs and H3Rs play different roles in gastric acid secretion, it is very important to verify that NAMH is a H2R agonist. AIMS: To determine whether NAMH is a H2R agonist, as well as a H3R agonist. METHODS: We used a Chinese hamster ovary (CHO) cell line expressing human H2Rs (CHO-H2R) and control CHO cells. Expression of human H2Rs was confirmed by tiotidine binding. cAMP production in CHO-H2R and control cells in response to histamine or NAMH was measured. cAMP production in response to 10(-7) M NAMH was also measured in the presence or absence of the H2R antagonist famotidine and the H3R antagonist thioperamide. RESULTS: NAMH dose dependently stimulated cAMP productions in CHO-H2R cells. This production was inhibited by famotidine but not by thioperamide. Control CHO cells were unresponsive to either histamine or NAMH. In addition, the effect of NAMH, in terms of cAMP production in CHO-H2R cells, was more potent than that of histamine-that is, with a lower EC(50) concentration and higher maximal cAMP production. Both NAMH and histamine, but not R-alpha-methyl-histamine, effectively inhibited [(3)H] tiotidine binding to CHO-H2R cells. CONCLUSIONS: NAMH, which is produced in the gastric mucosa by H pylori, is a potent H2R agonist as well as a H3R agonist.

Animals↗

The proportion of cells with functional X disomy is associated with the severity of mental retardation in mosaic ring X Turner syndrome females.

Turner syndrome females (45,X) do not have mental retardation (MR), whereas some mosaic ring X Turner syndrome females, with 45,X/46,X,r(X), have severe MR. The MR is believed to be caused by a failure of X chromosome inactivation (XCI) of the small ring X chromosome, which leads to functional X disomy (FXD), To explore this hypothesis, we examined the proportion of FXD cells in the peripheral blood of four ring X Turner syndrome females with various levels of MR, using two newly developed XCI assays based on DNA methylation of X-linked genes. As a result, the two patients with extremely severe MR showed complete FXD patterns, whereas the remaining two patients with relatively milder MR showed partial FXD patterns. These results indicate that the proportion of FXD cells may be associated with the severity of MR in mosaic ring X Turner syndrome females, although this association should be confirmed by examining brain cells during development. One of the cases with severe MR and a complete FXD pattern neither lacked the XIST gene nor had uniparental X isodisomy, and we discuss the mechanism of the failure of XCI in this case.

Child↗

[Veno-venous ECMO for the respiratory failure after coronary artery bypass grafting].

We encountered a 60-year-old man with severe respiratory failure after CABG. The patient received veno-venous extracorporeal membrane oxygenation (ECMO) in which blood was drained from the right atrium through a cannula and was returned via a cannula in the left femoral vein. During ECMO, the flow rate was 2.8-3.0 l/min (about 40 ml/kg/min) and the assist was needed for 5 years. Veno-venous ECMO is a simple and effective therapy for acute respiratory failure unresponsive to conventional treatment.

Acute Disease↗

FISH analysis for apparently simple terminal deletions of the X chromosome: identification of hidden structural abnormalities.

We report on fluorescence in situ hybridization (FISH) analysis in 30 mosaic or nonmosaic females diagnosed as having apparently simple terminal X deletions by standard G-banding analysis. FISH studies for DXZ1, the Xp and Xq telomere regions, and the whole X chromosome painting were carried out for the 30 females, indicating rearranged X chromosomes with signal patterns discordant with terminal deletions in 6 cases: one dic(X)(DXZ1++) chromosome, two der(X)(qtel++) chromosomes, one Xq- (qtel+) chromosome, and two der(X)(ptel++) chromosomes. Additional FISH studies were performed for the 6 cases using probes defining 12 loci on the X chromosome, showing large Xp deletion and small Xp duplication in the dic(X)(DXZ1++) chromosome, partial Xp deletions and partial Xq duplications in the two der(X)(qtel++) chromosomes, an interstitial Xq deletion in the Xq- (qtel+) chromosome, and partial Xq deletions and partial Xp duplications in the two der(X)(ptel++) chromosomes. Clinical assessment of the 6 cases revealed tall and normal stature in the two mosaic cases with the der(X)(ptel++) chromosomes that were shown to be associated with SHOX duplication. The results suggest that unusual X chromosome rearrangements are often misinterpreted as simple terminal X deletions, and that FISH analysis is useful for precise structural determination and better genotype-phenotype correlation of the X chromosome aberrations.

Adult↗