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Biomedical subjects

Y Takada

Publications and source records attributed to Y Takada.

At least 55 records · Page 3Linked to original sources

Bezafibrate attenuates the overexpression of plasminogen activator inhibitor-1 messenger RNA by a combination of mono-unsaturated fatty acid and insulin in hepG2 cells.

The effects of bezafibrate (PPAR alpha activator) and troglitazone (PPAR gamma activator) on the expression of plasminogen activator inhibitor type-1 (PAI-1) in HepG2 cells were investigated. Exposure of the cells for 24 hours to either oleic acid or insulin showed no obvious effects on PAI-1 synthesis, whereas the combination of the two agents induced a 2.3-fold increase in PAI-1 synthesis, which was accompanied by a 3-fold increase in both the 2.2 kb and 3.2 kb forms of PAI-1 mRNA. This up-regulation of PAI-1 synthesis was attenuated by bezafibrate in a dose-dependent manner (1-100 microM) with 30% reversal at 100 microM. In contrast, troglitazone further stimulated PAI-1 synthesis to 140% of the level obtained in the presence of both oleic acid and insulin. This attenuation by bezafibrate and enhancement by troglitazone required the presence of both oleic acid and insulin. It is interesting that PAI-1 expression was affected so differently by these two PPAR activators.

Bezafibrate↗

Requirement for natural killer T (NKT) cells in the induction of allograft tolerance.

In this study, we investigated the role of Valpha14 natural killer T (NKT) cells in transplant immunity. The ability to reject allografts was not significantly different between wild-type (WT) and Valpha14 NKT cell-deficient mice. However, in models in which tolerance was induced against cardiac allografts by blockade of lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions, long-term acceptance of the grafts was observed only in WT but not Valpha14 NKT cell-deficient mice. Adoptive transfer with Valpha14 NKT cells restored long-term acceptance of allografts in Valpha14 NKT cell-deficient mice. The critical role of Valpha14 NKT cells to mediate immunosuppression was also observed in vitro in mixed lymphocyte cultures in which lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions were blocked. Experiments using IL-4- or IFN-gamma-deficient mice suggested a critical contribution of IFN-gamma to the Valpha14 NKT cell-mediated allograft acceptance in vivo. These results indicate a critical contribution of Valpha14 NKT cells to the induction of allograft tolerance and provide a useful model to investigate the regulatory role of Valpha14 NKT cells in various immune responses.

Adaptation, Physiological↗

Role of platelet-activating factor in hepatectomy with Pringle's maneuver.

BACKGROUND: Interruption of hepatic inflow is commonly used to reduce blood loss during extensive liver resection, but may cause liver dysfunction. The present study investigated the effects of platelet-activating factor (PAF) antagonist E5880 on total liver warm ischemia and 70% hepatectomy. METHODS: Rabbits were used in this study and were divided into four groups: group 1, those treated with only 70% hepatectomy; group 2, those treated with only 20 min Pringle's maneuver; group 3, those treated with both Pringle's maneuver and 70% hepatectomy without pretreatment; and group 4, those pretreated with PAF antagonist E5880 (0.3 mg/kg) followed by Pringle's maneuver and 70% hepatectomy. The remnant liver function was then evaluated after reperfusion. RESULTS: Seven-day survival rates in both groups 1 and 2 were 100%. E5880 treatment significantly increased 7-day survival rate (group 4: 38% vs group 3: 0%, P < 0.05) after a combination of Pringle's maneuver and 70% hepatectomy. The elevations of serum liver enzymes (GOT, GPT, mGOT, and LDH) were significantly inhibited in group 4 at 1 and 4 h after reperfusion. Portal venous pressure and the energy charge of liver were also significantly improved in group 4, compared with those in group 3. Endothelin-1 levels of arterial and portal venous blood progressively increased after reperfusion; however, there were no significant differences between the two groups. Leukocyte infiltration into the liver was significantly inhibited in group 4. CONCLUSION: E5880 pretreatment has protective effects on liver function after 70% hepatectomy with Pringle's maneuver in rabbits.

Adenine Nucleotides↗

Platelet integrin alphaIIbbeta3-ligand interactions: what can we learn from the structure?

Upon vascular injury, platelets initiate interaction with exposed subendothelial matrices through various receptors such as glycoprotein (GP) Ib/IX/V complex, alpha2beta1 integrin, and GPVI/FcRgamma. Although these interactions cannot sustain stable platelet thrombus formation by themselves, they ultimately lead to the activation of alphaIIbbeta3 integrin (GPIIb-IIIa complex [GPIIb-IIIa]), the most abundant receptor in platelets. The alphaIIbbeta3 integrin plays a central role in primary hemostasis by serving as a receptor for fibrinogen and von Willebrand factor (vWf). It establishes a stable interaction with vWf bound to the extracellular matrices and uses fibrinogen as a bridging molecule in platelet aggregate formation. The alphaIIbbeta3 integrin also plays an important role in the pathogenesis of thrombosis. Over the past decades, a tremendous amount of effort has been made to elucidate the ligand-binding mechanisms of alphaIIbbeta3, in part because of its clinical significance. Most of the studies have relied on biochemical analyses of purified alphaIIbbeta3 or recombinant proteins generated in vitro. With the lack of actual 3-dimensional structure, molecular modeling has provided a useful framework for interpreting such experimental data on structure-function correlation of integrin molecules. However, it has also generated disagreement between different models. The aim of this minireview is to summarize the past efforts as well as the recent accomplishments in elucidating the structure/function of alphaIIbbeta3. Finally, we will try to explain all those experimental data using the recently published crystal structure of the extracellular domains of the alphaVbeta3 heterodimeric complex.

Animals↗

Age-related differences in postural control in humans in response to a sudden deceleration generated by postural disturbance.

Age-related differences in postural control in response to a relatively large deceleration resulting from postural disturbance were investigated in eight normal elderly men (age range 67-72 years) and eight young men as controls (age range 19-22 years) using a moving platform. Data were obtained for the hip, knee and ankle angles, position of the centre of foot pressure (CFP), head acceleration, and muscle activity of the leg muscles. The elderly subjects had slower and larger ankle and hip joint movements, and CFP displacement in response to the disturbance compared to the young controls. The elderly subjects also had a delayed occurrence, and greater magnitude of peak acceleration of head rotation than did the young subjects. For the elderly subjects, the CFP was closely related to angular changes in the hip joint movement, but not to those of the ankle and knee joint movements. For the young subjects, on the other hand, the CFP was significantly correlated with angular change in the ankle joint. Cocontraction of the tibialis anterior and gastrocnemius muscles was observed in the elderly subjects. The results indicated that a movement pattern for postural correction in the elderly adults was different from that of the young adults. The elderly relied more on hip movements while the young controls relied on ankle movements to control postural stability.

Adult↗

Relationship between fear of falling and balancing ability during abrupt deceleration in aged women having similar habitual physical activities.

The purpose of this study was to evaluate the influence of fear of falling on balancing ability during abrupt deceleration in aged women. The subjects were 20 women aged between 67 and 75 years. They were classified into two groups, one having a fear of falling (group FF, n = 10) and another without this fear (group NFF, n = 10). The two groups had similar daily physical activities. Changes in the centre of foot pressure (CFP) were measured during postural sway following horizontal deceleration of the force platform on which they were standing, and the response time and CFP displacement were evaluated. In addition, the electromyogram (EMG) onset in the tibialis anterior muscle and medial gastrocnemius muscle during abrupt deceleration, and its difference between the two muscles were measured. and the relative level of co-contraction of antagonistic muscles (the co-contraction index, CCI) in the lower extremity muscle group was calculated. The response time and CFP displacement immediately after abrupt deceleration were significantly higher in group FF than in NFF (P < 0.05). The EMG onset in the two muscles did not significantly differ between the two groups. The difference in EMG onset between the two muscles was significantly lower in group FF than in NFF (P < 0.05). The CCI was significantly higher in group FF than in NFF (P < 0.05). These results suggest that there were negative effects of a fear of falling on the balancing ability immediately after abrupt deceleration. This may be because a fear of falling increases the co-contraction of antagonist muscles in the lower extremity muscle group.

Aged↗

Trigeminal neuralgia associated with achondroplasia. Case report with literature review.

A 59-year-old male with a history of 2 years of typical trigeminal neuralgia manifested the characteristics of achondroplasia. X-ray and magnetic resonance imaging demonstrated basilar impression, deformity of the posterior fossa with marked asymmetry of petrous bone and compression of pons and trigeminal nerve by the left vertebral artery and anterior inferior cerebellar artery. Microvascular decompression was performed through a suboccipital craniectomy. The neuralgia disappeared soon after surgery and remains completely resolved until today. This is the first reported case of trigeminal neuralgia in a patient with achondroplasia. The deformity of the skull base was considered to influence the development of the trigeminal neuralgia.

Achondroplasia↗

Bronchoscopic dye injection for localization of small pulmonary nodules in thoracoscopic surgery.

A new method of marking small pulmonary nodules situated deep within the visceral pleura using a transbronchial approach has been developed. Once the tip of the sheath catheter has passed the tumor and reached the visceral pleura, as confirmed by computed tomography fluoroscopy, indigo carmine is injected through a bronchoscope into the lung parenchyma just beneath the visceral pleura. No complications related to the procedure were experienced. The dye-marking procedure enabled the nodules to be precisely located. This technique can provide appropriate guidance when used in conjunction with video-assisted thoracic operations.

Bronchoscopy↗

Bond strength of binary titanium alloys to porcelain.

The purpose of this study was to investigate the bond strength between porcelain and experimental cast titanium alloys. Eleven binary titanium alloys were examined: Ti-Cr (15, 20, 25 wt%), Ti-Pd (15, 20, 25 wt%), Ti-Ag (10, 15, 20 wt%), and Ti-Cu (5, 10 wt%). As controls, the bond strengths for commercially pure titanium (KS-50, Kobelco, Japan) and a high noble gold alloy (KIK, Ishifuku, Japan) were also examined. Castings were made using a centrifugal casting unit (Ticast Super R, Selec Co., Japan). Commercial porcelain for titanium (TITAN, Noritake, Japan) was applied to cast specimens. The bond strengths were evaluated using a three-point bend test according to ISO 9693. Since the elastic modulus value is needed to evaluate the bond strength, the modulus was measured for each alloy using a three-point bend test. Results were analyzed using one-way ANOVA/S-N-K test (alpha = 0.05). Although the elastic moduli of the Ti-Pd alloys were significantly lower than those of other alloys (p = 0.0001), there was a significant difference in bond strength only between the Ti-25Pd and Ti-15Ag alloys (p = 0.009). The strengths determined for all the experimental alloys ranged from 29.4 to 37.2MPa, which are above the minimum value required by the ISO specification (25 MPa).

Dental Alloys↗

Endoscopic findings of radiation esophagitis in concurrent chemoradiotherapy for intrathoracic malignancies.

BACKGROUND AND PURPOSE: The incidence and extent of radiation esophagitis were assessed endoscopically in patients treated with concurrent chemoradiotherapy. PATIENTS AND METHODS: Eighty-two patients who received thoracic radiotherapy for lung, thymic, or esophageal cancer were investigated endoscopically from July 1991 to the end of 1997. Among them, 23 esophageal cancer patients were treated with radiation alone, and the others were treated with concurrent chemoradiotherapy. Esophageal endoscopy was performed during or just after radiotherapy. The presence of radiation esophagitis was assessed and assigned an endoscopic score (i.e. grade 0 for normal, 1 for erythema, 2 for erosion or sloughing, 3 for ulcer, hemorrhage, or stricture). The symptomatic grade was assessed using the RTOG (Radiation Therapy Oncology Group) acute radiation morbidity score. RESULTS: A correlation was seen between endoscopic and RTOG scores. However, even some patients with RTOG grade 0 to 1 had endoscopic grade 3 esophagitis. Endoscopic grade 3 was observed in 16 (27.1%) patients in the concurrent chemoradiotherapy group, whereas it did not occur in any patient in the radiation alone group (P=0.004). CONCLUSIONS: Our results suggest that (1) RTOG score correlates closely to esophageal mucosal damage, and (2) more severe esophagitis occurs in those undergoing concurrent chemoradiotherapy than those undergoing radiotherapy alone [corrected].

Adult↗

Effects of fibronectin cleaved by neuropsin on cell adhesion and migration.

Neuropsin is a serine protease cloned from the mouse hippocampus. Since neuropsin is a secreted protein which effectively cleaves fibronectin, it may affect cell adhesion or cell migration by modulating the content and/or chemical characteriscs of fibronectin in extracellular matrix (ECM). In adhesion assays, alpha5B2 cells expressing integrin alpha5beta1 bound less effectively to fibronectin teated with neuropsin than intact fibronectin. In Boyden chamber chemotaxis assays, the fibronectin-induced migration of alpha5B2 cells was not affected by neuropsin treatment. These findings suggest that neuropsin regulates the local microenvironment by modulating the interaction between cells and fibronectin in ECM.

Animals↗

Dissociation of systemic and hippocampal modulation of rat locomotor activity by 5-HT(2C) receptors.

In the present study, the ability of 5-hydroxytryptamine(2C) (5-HT(2C)) receptors in the hippocampus to enhance locomotor activity in rats was investigated by local infusion. Intraperitoneal injection of the selective 5-HT(2C) antagonist SB 242084 (1 mg/kg) significantly increased rats motor activity, while the effects of non-selective 5-HT(2C) agonist m-chlorophenylpiperazine (m-CPP, 10 mg/kg; i.p.) on motor activity were lower than those of the control group. In the day hours, the local infusion of non-selective 5-HT(2C) agonist, m-CPP (1.0 mM) into the bilateral hippocampus via microdialysis probes increased locomotor activity in contrast with intraperitoneal injection. This increase was completely reversed by the combined infusion of the selective 5-HT(2C) antagonist SB 242084 (100 mM). In the night hours, the local infusion of SB 242084 (100 mM) into the bilateral hippocampus significantly inhibited the nocturnal hyperactivity, which was reversed by the combined infusion of m-CPP. The present study demonstrates that the 5-HT(2C) receptors in the hippocampus act to increase rat locomotor activity.

Aminopyridines↗

Increased intracranial pressure in a porcine model of fulminant hepatic failure using amatoxin and endotoxin.

BACKGROUND/AIMS: The purpose of this study was to develop a clinically relevant porcine model of fulminant hepatic failure (FHF) by means of administration of amatoxin and endotoxin. METHODS: Pigs were intraportally administered only saline in group 1 (n = 3), 1 microg/kg of lipopolysaccharide (LPS) in group 2 (n = 4), 0.1 mg/kg of alpha-amanitin in group 3 (n = 5), and amanitin plus LPS in group 4 (n = 9). RESULTS: All the pigs in groups 1 and 2 survived with minimal changes in liver function tests. In contrast to the 60% mortality in group 3, all the pigs in group 4 died within 96 h, with a significant increase in aspartate transaminase at 24 h (9,757 +/- 2,167 IU/I). In addition, they demonstrated severe metabolic disorders, such as serum lactate accumulation, hypoglycemia, coagulopathy, plasma amino acid imbalance, and hyperammonemia. The intracranial pressure significantly increased to 17.8 +/- 2.5 mmHg immediately before death. Reversal of FHF in these pigs following orthotopic liver transplantation confirmed that the toxicity is liver-specific and that the graft liver is unaffected. CONCLUSIONS: This porcine model of FHF induced by a combination of amanitin and LPS will be of much use in the development of new therapies for human FHF.

Amanitins↗

The differential effect of angiotensin II and angiotensin 1-7 on norepinephrine, epinephrine, and dopamine concentrations in rat hypothalamus: the involvement of angiotensin receptors.

Angiotensin 1-7 has been recently claimed the active member of the angiotensins' family. In the present study we compared the effect of angiotensin II and angiotensin 1-7 on the concentration of dopamine, serotonin, epinephrine, and norepinephrine and some of their metabolites in the rat hypothalamus, where the levels of angiotensins are particularly high. Intracerebroventricular injection of angiotensin II, but not angiotensin 1-7, time-dependently elevated the levels of both epinephrine (p < 0.05) and norepinephrine (p < 0.05) in the hypothalamus and both effects could be prevented by intracerebroventricular injection of either AT(1) (candesartan), AT(2) (PD123319) or AT(1-7) (A-779) receptor antagonist. Neither angiotensin II nor angiotensin 1-7 produced any changes in the level of dopamine, dihydroxyphenylacetic acid, homovanilic acid, serotonin, 5-hydroxyindoleacetic acid, or tryptophan at any time point in comparison with the control groups. However, AT(1) but not AT(2) receptor blockade, unmasked the stimulatory effect of angiotensin 1-7 on dopamine concentration in the hypothalamus. Thus, angiotensin II and its active metabolite angiotensin 1-7 regulate selectively, albeit differentially, adrenergic, noradrenergic and dopaminergic systems in the hypothalamus, the effects that involve AT(1), AT(2) and AT(1-7) angiotensin receptors.

3,4-Dihydroxyphenylacetic Acid↗

Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site.

The beta2 integrin leukocyte function antigen-1 (LFA-1) has an important role in the pathophysiology of inflammatory and autoimmune diseases. Here we report that statin compounds commonly used for the treatment of hypercholesterolemia selectively blocked LFA-1-mediated adhesion and costimulation of lymphocytes. This effect was unrelated to the statins' inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A reductase; instead it occurred via binding to a novel allosteric site within LFA-1. Subsequent optimization of the statins for LFA-1 binding resulted in potent, selective and orally active LFA-1 inhibitors that suppress the inflammatory response in a murine model of peritonitis. Targeting of the statin-binding site of LFA-1 could be used to treat diseases such as psoriasis, rheumatoid arthritis, ischemia/reperfusion injury and transplant rejection.

Allosteric Site↗

Nrl is required for rod photoreceptor development.

The protein neural retina leucine zipper (Nrl) is a basic motif-leucine zipper transcription factor that is preferentially expressed in rod photoreceptors. It acts synergistically with Crx to regulate rhodopsin transcription. Missense mutations in human NRL have been associated with autosomal dominant retinitis pigmentosa. Here we report that deletion of Nrl in mice results in the complete loss of rod function and super-normal cone function, mediated by S cones. The photoreceptors in the Nrl-/- retina have cone-like nuclear morphology and short, sparse outer segments with abnormal disks. Analysis of retinal gene expression confirms the apparent functional transformation of rods into S cones in the Nrl-/- retina. On the basis of these findings, we postulate that Nrl acts as a 'molecular switch' during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of Nr2e3.

Animals↗

Prolongation of activation-recovery interval over a preexcited region before and after catheter ablation in patients with Wolff-Parkinson-White syndrome.

INTRODUCTION: Preexisting changes in repolarization properties play an important role in T wave abnormalities (cardiac memory) after ablation in patients with Wolff-Parkinson-White (WPW) syndrome. However, no report has provided direct evidence for prolongation of action potential duration (APD) over a preexcited region before and after ablation. METHODS AND RESULTS: We studied 10 patients with ventricular preexcitation due to a left-sided accessory pathway (AP) (group M) and 12 patients with concealed left-sided AP (group C) to clarify prolongation of APD using activation-recovery intervals (ARIs) from epicardial and endocardial unipolar electrograms in patients with WPW syndrome. ARI was calculated from unipolar electrograms at the His bundle and the coronary sinus adjacent to the AP during atrial pacing (100 beats/min) before and 30 minutes after ablation. Before ablation, ARIs at the AP site were significantly longer in group M than in group C (255+/-21 msec vs 211+/-24 msec; P < 0.01), whereas ARIs at the His bundle did not differ between the two groups (255+/-20 msec vs 245+/-27 msec; P = NS). After ablation, group M showed no significant changes in ARIs at the AP and His bundle (256+/-19 msec and 253+/-15 msec) compared with before ablation. CONCLUSION: We found by direct analysis of ARIs from the epicardium that APD prolongation over the preexcited region was present before catheter ablation and persisted after catheter ablation. The gradual changes in repolarization properties, including APD prolongation after discontinuation of AP, may be one mechanism of cardiac memory after catheter ablation in patients with WPW syndrome.

Action Potentials↗