Ablation of MEK kinase 1 suppresses intimal hyperplasia by impairing smooth muscle cell migration and urokinase plasminogen activator expression in a mouse blood-flow cessation model.

Background: Migration, proliferation, and matrix-degrading protease expression of smooth muscle cells (SMCs) are major features of intimal hyperplasia after vascular injury. Although MEK kinase 1 (MEKK1) has been shown to regulate cell migration and urokinase plasminogen activator (uPA) expression, the precise role of MEKK1 in this process remains unknown.

Methods And Results: We triggered a vascular remodeling model by complete ligation of the right common carotid artery in wild-type (WT) and MEKK1-null (MEKK1-/-) mice.

A case report of the effect of plasma exchange on reactive hemophagocytic syndrome associated with toxic shock syndrome.

We report here the case of a patient suffering from hemophagocytic syndrome (HPS) associated with toxic shock syndrome (TSS). A 50-year-old man was admitted because of fever, watery diarrhea and shortness of breath. Clinical analysis revealed systemic cyanosis, sunburn-like erythema and septic shock.

Selective blockade of serotonin 5-HT2A receptor increases coronary blood flow via augmented cardiac nitric oxide release through 5-HT1B receptor in hypoperfused canine hearts.

Serotonin (5-hydroxytryptamine [5-HT]), which induces vasoconstriction via 5-HT2A receptors in smooth muscle cells and vasodilation through activating nitric oxide (NO) synthase (NOS) via 5-HT1B receptors in endothelial cells, possesses divergent effects on regulating vascular tone. These facts lead us to consider that sarpogrelate, a 5-HT2A receptor blocker, may increase coronary blood flow (CBF) via either attenuation of vasoconstriction through 5-HT2A receptor blockade or augmentation of vasodilation by relative stimulation of NOS through 5-HT1B receptor and we tested this hypothesis in ischemic canine hearts. In open chest dogs, coronary perfusion pressure was reduced so that CBF was decreased to 33% of the baseline and kept constant.

Opening of Ca2+-activated K+ channels is involved in ischemic preconditioning in canine hearts.

Brief periods of ischemia that precede sustained ischemia can markedly reduce infarct size (IS), a phenomenon that is known as ischemic preconditioning (IP). Several investigators have shown that elevation of the intracellular Ca(2+) level ([Ca(2+)](i)) during the antecedent brief periods of ischemia triggers the cardioprotective mechanism of IP. Since opening of Ca(2+) activated K(+) (K(Ca)) channels is reported to be cardioprotective, we hypothesized that these channels may be involved in the cardioprotective mechanism of IP.

[Effect of development and aging on the modified Wisconsin Card Sorting Test in normal subjects].

The Wisconsin card sorting test (WCST) is applied to various types of neurological disorders. Since WCST requires the examinee's sustained efforts, it is not readily applicable to children with developmental disorders. In order to overcome this weakness, Keio version WCST (KWCST) was developed by reducing the number of cards from 128 to 48 and presenting them in two steps separated by a short pause.

Ischemic preconditioning: emerging evidence, controversy, and translational trials.

Protection against ischemia by ischemic preconditioning (IP) is seen in many tissues and organs. However, the preconditioning ischemia must precede lethal ischemia for this effect to occur, and the creation of ischemia to treat heart disease does not seem to be a realistic strategy. Accordingly, the underlying mechanisms that confer cardioprotection should be identified.

Optimal windows of statin use for immediate infarct limitation: 5'-nucleotidase as another downstream molecule of phosphatidylinositol 3-kinase.

Background: Although statins are reported to have a cardioprotective effect, their immediate direct influence on ischemia-reperfusion injury and the underlying mechanisms remain obscure. We investigated these issues an in vivo canine model.

Methods And Results: Dogs were subjected to coronary occlusion (90 minutes) and reperfusion (6 hours) immediately after injection of pravastatin (0.

Breathing chest radiography using a dynamic flat-panel detector combined with computer analysis.

Kinetic information is crucial when evaluating certain pulmonary diseases. When a dynamic flat-panel detector (FPD) can be used for a chest examination, kinetic information can be obtained simply and cost-effectively. The purpose of this study was to develop methods for analyzing respiratory kinetics, such as movement of the diaphragm and lung structures, and the respiratory changes in x-ray translucency in local lung fields.

Celiprolol, a vasodilatory beta-blocker, inhibits pressure overload-induced cardiac hypertrophy and prevents the transition to heart failure via nitric oxide-dependent mechanisms in mice.

Background: The blockade of beta-adrenergic receptors reduces both mortality and morbidity in patients with chronic heart failure, but the cellular mechanism remains unclear. Celiprolol, a selective beta(1)-blocker, was reported to stimulate the expression of endothelial NO synthase (eNOS) in the heart, and NO levels have been demonstrated to be related to myocardial hypertrophy and heart failure. Thus, we aimed to clarify whether celiprolol attenuates both myocardial hypertrophy and heart failure via the NO-signal pathway.

[A case of primary signet ring cell carcinoma of the urinary bladder presenting as nocturnal incontinence].

This is a report of our experience of a case of primary signet ring cell carcinoma of the urinary bladder. The patient was a 56-year-old man who was referred to our hospital presenting with incontinence and lumbago. A drip infusion pyelography study indicated bilateral hydronephrosis and a contracted bladder.

Protein kinase A as another mediator of ischemic preconditioning independent of protein kinase C.

Background: We and others have reported that transient accumulation of cyclic AMP (cAMP) in the myocardium during ischemic preconditioning (IP) limits infarct size independent of protein kinase C (PKC). Accumulation of cAMP activates protein kinase A (PKA), which has been demonstrated to cause reversible inhibition of RhoA and Rho-kinase. We investigated the involvement of PKA and Rho-kinase in the infarct limitation by IP.

Raloxifene improves coronary perfusion, cardiac contractility, and myocardial metabolism in the ischemic heart: role of phosphatidylinositol 3-kinase/Akt pathway.

The purpose of this study is to examine whether raloxifene, one of the selective estrogen receptor modulators, could improve myocardial ischemia and to assess the mechanisms involved. In open-chest beagle dogs anesthetized by intravenous infusion of sodium pentobarbital, the left anterior descending coronary artery (LAD) was perfused from the left carotid artery through an extracorporeal bypass tube. Raloxifene was infused into the LAD through the bypass tube under either ischemic or non-ischemic conditions.

Beta-adrenoceptor blocker carvedilol provides cardioprotection via an adenosine-dependent mechanism in ischemic canine hearts.

Background: Carvedilol is a beta-adrenoceptor blocker with a vasodilatory action that is more effective for the treatment of congestive heart failure than other beta-blockers. Recently, carvedilol has been reported to reduce oxidative stress, which may consequently reduce the deactivation of adenosine-producing enzymes and increase cardiac adenosine levels. Therefore, carvedilol may also have a protective effect on ischemia and reperfusion injury, because adenosine mediates cardioprotection in ischemic hearts.

Methotrexate and MX-68, a new derivative of methotrexate, limit infarct size via adenosine-dependent mechanisms in canine hearts.

Methotrexate, an anti-rheumatic agent, has recently been reported to show an anti-inflammatory action via ecto-5'-nucleotidase- and adenosine-dependent mechanisms. Because ecto-5'-nucleotidase contributes to the production of adenosine and adenosine has a potent cardioprotective effect against ischemia/reperfusion injury, we investigated whether methotrexate or MX-68 [N-1-((2,4-diamino-6-pteridinyl) methyl)-3,4-dihydro-2H-1,4-benzothiazine-7- carbonyl]-N-2- aminoadipic acid] could reduce infarct size via adenosine-dependent mechanisms. In beagle dogs, the left anterior descending coronary artery was perfused through a bypass tube, which was occluded for 90 minutes followed by 6 hours of reperfusion.

[Hepatic perfusion CT imaging analyzed by the dual-input one-compartment model].

Aim: To improve liver-perfusion imaging by using the dual-input one-compartmental model.

Methods: Single-level dynamic computed tomography (dynamic CT) was taken at the height of the hepatic hilum after a rapid intravenous injection using 40 ml of iodinated contrast material. From the time-density curve of each pixel on CT, we calculated blood-flow rate constants of liver inflow and outflow.

[Development of automated segmentation method for the posterior portion of the temporal lobe on coronal MR images].

Brain MRI is an important method for examining the diseases caused by various cerebral pathologies, and the measurement of temporal lobe volume is useful for identifying dementia and temporal lobe abnormalities. However, no segmentation algorithm for the temporal lobe on coronal MR images has been established. Such an algorithm is needed because the shape of the temporal lobe on coronal images varies from area to area.

Quantitative perfusion map of malignant liver tumors, created from dynamic computed tomography data.

Rationale And Objectives: To apply perfusion computed tomography (CT) technique to variable malignant liver tumors, and to define the usefulness of quantitative color mapping.

Materials And Methods: Perfusion CT images were created for 36 malignant liver tumors in 28 patients (age, 66.4 +/- 10.

Lamr1 functional retroposon causes right ventricular dysplasia in mice.

Arrhythmogenic right ventricular dysplasia (ARVD) is a hereditary cardiomyopathy that causes sudden death in the young. We found a line of mice with inherited right ventricular dysplasia (RVD) caused by a mutation of the gene laminin receptor 1 (Lamr1). This locus contained an intron-processed retroposon that was transcribed in the mice with RVD.

[Screening chest X-ray examination with kinetic analysis using flat-panel detector].

We are developing dynamic screening radiography to provide kinetic information for lung respiratory examination using a flat-panel-detector (FPD) system. We modified the FPD system (CANON CXDI-22) to take sequential images for a short period of time (10 seconds, 3 frames/sec). Sequential chest radiographs from full inspiration to expiration were taken and analyzed for diaphragm movement and density changes in local lung areas to objectively detect respiratory anomalies.

Raloxifene prevents cardiac hypertrophy and dysfunction in pressure-overloaded mice.

17beta-estradiol reduces myocardial hypertrophy and left ventricular mass, suggesting that the selective estrogen receptor modulator raloxifene may have similar effects. However, it is not clear whether raloxifene inhibits both cardiac hypertrophy and dysfunction. We used transverse aortic-banded mice to produce pressure-overload cardiac hypertrophy and used neonatal rat ventricular cardiomyocytes to investigate the cellular mechanisms of raloxifene on cardiac hypertrophy.

Activation of adenosine A1 receptor attenuates cardiac hypertrophy and prevents heart failure in murine left ventricular pressure-overload model.

Sympathomimetic stimulation, angiotensin II, or endothelin-1 is considered to be an essential stimulus mediating ventricular hypertrophy. Adenosine is known to protect the heart from excessive catecholamine exposure, reduce production of endothelin-1, and attenuate the activation of the renin-angiotensin system. These findings suggest that adenosine may also attenuate myocardial hypertrophy.

[Development of breathing chest radiography: study of exposure timing].

The flat-panel detector (FPD) has been introduced into clinical practice. A modified FPD, which has the ability to obtain dynamic chest radiographs, was introduced into our hospital, and clinical testing is ongoing. Both the inspiratory and expiratory phases have to be included in dynamic chest radiographs.