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S Takeda

Publications and source records attributed to S Takeda.

At least 145 records · Page 8Linked to original sources
PubMed2000

Angiotensin II-induced cardiomyocyte hypertrophy and cardiac fibrosis in stroke-prone spontaneously hypertensive rats.

Angiotensin-converting enzyme inhibitors (ACEIs) cause regression of hypertensive left ventricular hypertrophy (LVH) by reducing angiotensin II, increasing bradykinin, or both. The mechanisms of these cardioprotective effects remain controversial. The aims of this study were to determine whether the cardioprotective effects of ACEIs are mediated by reducing angiotensin II and whether ACEIs ameliorate the morphologic, physiologic, and biochemical changes in the hearts of stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs were treated with hydralazine, captopril, or candesartan, an angiotensin II type 1 receptor (AT1R) antagonist, from age 12 to 24 weeks. We measured systolic blood pressure (SBP), left ventricular weight (LVW), left ventricular (LV) myocyte cross-sectional area (myocyte size), LV Interstitial collagen volume fraction (ICVF), perivascular collagen area/luminal area ratio (PVCA/LA), the medial area to luminal area ratio (MA/LA), the relative amount of V3 myosin heavy chain (MHCV3), and coronary reserve maximum (coronary flow max/ventricular weight (CFmax/VW)). These parameters were compared with those of untreated SHRSPs and Wistar-Kyoto rats (WKYs). SHRSPs exhibited decreased coronary reserve and LVH with an increase in myocyte size, PVCA/LA, MA/LA, and MHCV3 at 12 weeks of age. In addition to these changes, 24-week-old SHRSPs showed an increase in ICVF. The LVW, coronary reserve, myocyte size, PVCA/LA, ICVF, and MHCV3 of SHRSPs treated with captopril or candesartan all approached control values. In contrast, hydralazine decreased only ICVF. These results suggest that ACEIs regress LVH and normalize coronary reserve by modulating the effects of angiotensin II via AT1R on the induction of cardiomyocyte hypertrophy, perivascular fibrosis, and medial thickening of intramyocardial coronary arteries in SHRSPs. We concluded that these effects, in addition to the reduction of SBP, are important in causing the regression of LVH.

Angiotensin Receptor Antagonists↗
PubMed2000

Neutrophils express tissue factor in a monkey model of sepsis.

BACKGROUND: Although tissue factor (TF) is involved in hemostasis, thrombogenesis, inflammation, and cellular immune response, its source in sepsis remains controversial. Recently, we found that, in addition to monocytes and endothelial cells, neutrophils may express TF in a rabbit model. The purpose of this study was to determine whether neutrophils could be a source of TF in a monkey model of sepsis. METHODS: TF messenger RNA (mRNA) and protein in neutrophils were assayed by in situ hybridization and immunohistochemistry in tissues obtained from monkeys after injection of lipopolysaccharide (LPS) (n = 3) and after injection of saline as a control (n = 2). Coagulation parameters were measured before and at 1.5 and 3 hours after injections. RESULTS: In LPS-treated monkeys, TF mRNA and protein were induced not only in monocytes and endothelial cells, but also in neutrophils accumulating in the liver 3 hours after LPS injection. Thrombin-antithrombin III complex and fibrin degradation products D-dimer levels were significantly increased at 3 and 1.5 hours after LPS injection compared with controls. CONCLUSIONS: Neutrophils are a source of TF and are implicated in direct activation of the coagulation cascade in the early phases of sepsis in the monkey. These results give important information for the treatment of sepsis.

Animals↗
PubMed2000

Three-dimensional structure of 4-amino-4-deoxychorismate lyase from Escherichia coli.

4-Amino-4-deoxychorismate lyase (ADCL) is a member of the fold-type IV of PLP dependent enzymes that converts 4-amino-4-deoxychorismate (ADC) to p-aminobenzoate and pyruvate. The crystal structure of ADCL from Escherichia coli has been solved using MIR phases in combination with density modification. The structure has been refined to an R-factor of 20.6% at 2.2 A resolution. The enzyme is a homo dimer with a crystallographic twofold axis, and the polypeptide chain is folded into small and large domains with an interdomain loop. The coenzyme, pyridoxal 5'-phosphate, resides at the domain interface, its re-face facing toward the protein. Although the main chain folding of the active site is homologous to those of D-amino acid and L-branched-chain amino acid aminotransferases, no residues in the active site are conserved among them except for Arg59, Lys159, and Glu193, which directly interact with the coenzyme and play critical roles in the catalytic functions. ADC was modeled into the active site of the unliganded enzyme on the basis of the X-ray structures of the unliganded and liganded forms in the D-amino acid and L-branched-chain amino acid aminotransferases. According to this model, the carboxylates of ADC are recognized by Asn256, Arg107, and Lys97, and the cyclohexadiene moiety makes van der Waals contact with the side chain of Leu258. ADC forms a Schiff base with PLP to release the catalytic residue Lys159, which forms a hydrogen bond with Thr38. The neutral amino group of Lys159 eliminates the a-proton of ADC to give a quinonoid intermediate to release a pyruvate in accord with the proton transfer from Thr38 to the olefin moiety of ADC.

Amino Acid Sequence↗
PubMed2000

Stereochemistry of the transamination reaction catalyzed by aminodeoxychorismate lyase from Escherichia coli: close relationship between fold type and stereochemistry.

Aminodeoxychorismate lyase is a pyridoxal 5'-phosphate-dependent enzyme that converts 4-aminodeoxychorismate to pyruvate and p-aminobenzoate, a precursor of folic acid in bacteria. The enzyme exhibits significant sequence similarity to two aminotransferases, D-amino acid aminotransferase and branched-chain L-amino acid aminotransferase. In the present study, we have found that aminodeoxychorismate lyase catalyzes the transamination between D-alanine and pyridoxal phosphate to produce pyruvate and pyridoxamine phosphate. L-Alanine and other D- and L-amino acids tested were inert as substrates of transamination. The pro-R hydrogen of C4' of pyridoxamine phosphate was stereospecifically abstracted during the reverse half transamination from pyridoxamine phosphate to pyruvate. Aminodeoxychorismate lyase is identical to D-amino acid aminotransferase and branched-chain L-amino acid aminotransferase in the stereospecificity of the hydrogen abstraction, and differs from all other pyridoxal enzymes that catalyze pro-S hydrogen transfer. Aminodeoxychorismate lyase is the first example of a lyase that catalyzes pro-R-specific hydrogen abstraction. The result is consistent with recent X-ray crystallographic findings showing that the topological relationships between the cofactor and the catalytic residue for hydrogen abstraction are conserved among aminodeoxychorismate lyase, D-amino acid aminotransferase and branched-chain L-amino acid aminotransferase [Nakai, T., Mizutani, H., Miyahara, I., Hirotsu, K., Takeda, S., Jhee, K.-H., Yoshimura, T., and Esaki, N. (2000) J. Biochem. 128, 29-38].

Alanine↗
PubMed2000

Plasmon-loss imaging of chains of crystalline-silicon nanospheres and silicon nanowires

Nanostructures in chains of crystalline-silicon nanospheres and silicon nanowires were investigated using energy-filtered transmission electron microscopy (TEM). Observation of the shape of the silicon nanospheres in the chains provided the direct evidence that the chains were formed via the surface oxidation process, which may preferentially work at the necks. The diverse nanostructures in silicon nanowires were revealed, and we found smooth-shaped wires which have periodically modulated silicon cores. Nanostructures in wire-chain transition regions were also investigated for the first time. The wire-chain transition is not a simple junction of a silicon nanowire and a chain of silicon nanospheres, but has a periodically modulated silicon core in the wire region near the transition position.

Journal Article↗
PubMed2000

Splanchnic organ blood flow during calcitonin gene-related peptide-induced hypotension with or without propranolol in dogs.

UNLABELLED: Propranolol has been used to attenuate reflex tachycardia during induced hypotension. The purpose of the current study was to determine whether propranolol can modify splanchnic organ blood flow during calcitonin gene-related peptide (CGRP)-induced hypotension in dogs anesthetized with 1.3% isoflurane in oxygen. After surgical preparation and hemodynamic stabilization, saline as a control, 0.5 mg/kg and 2.0 mg/kg propranolol (n = 10, each) were administered in a bolus injection 20 min before hypotension was induced. Mean arterial pressure was reduced to 60 mm Hg during 60 min of CGRP infusion. Renal blood flow (RBF), hepatic blood flow (HBF), and pancreatic blood flow (PBF) were measured using the hydrogen clearance method. Cardiac index did not change in all three groups, and heart rate in the control group remained unchanged. In the propranolol groups, however, heart rate decreased (P < 0.01). Plasma norepinephrine (NE), but not epinephrine (E), increased (P < 0.05) after propranolol administration. The NE and E increased (P < 0.01) during induced hypotension in all three groups. NE was higher in the 0.5 mg/kg propranolol group than in the control group. RBF in the control group remained unchanged throughout observation. RBF, HBF, and PBF decreased (P < 0.01) after propranolol and remained decreased during and after induced hypotension. The degrees of decreased HBF and PBF in the control group were less than those in the 2.0 mg/kg propranolol group. In conclusion, pretreatment with propranolol decreases splanchnic organ blood flow further during CGRP-induced hypotension, due in part to increased plasma catecholamine concentrations. IMPLICATIONS: The reductions in splanchnic organ blood flows during CGRP-induced hypotension with propranolol are due to a reflex augmentation in sympathetic vasoconstrictor tone caused by an increase in plasma catecholamine concentrations. These findings suggest that propranolol may impair splanchnic organ blood flow during CGRP-induced hypotension.

Adrenergic beta-Antagonists↗
PubMed2000

Myocardial dysfunction associated with proinflammatory cytokines after esophageal resection.

UNLABELLED: Proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with major surgery. We investigated the profile of proinflammatory cytokines and the association of cytokine levels with myocardial function after esophagectomy. We studied 12 patients who underwent subtotal esophagectomy. One patient died of multiple organ failure. This patient had the largest interleukin-6 (IL-6) level of all the subjects. IL-6 levels increased from 14.9 +/- 8.7 pg/mL to 498.4 +/- 294.3 pg/mL (P < 0.05) at 6 h postoperatively. Interleukin-8 (IL-8) levels also significantly increased postoperatively. Right ventricular ejection fraction (RVEF) decreased from 44% +/- 1% to 36% +/- 2% (P < 0.05) and 37% +/- 2% (P < 0.05) at 6 h and 12 h postoperatively. Stroke volume index (SVI) decreased significantly at the end of operation and at 6 h and 12 h postoperatively. The changes of RVEF and SVI showed an independent negative correlation with the IL-6 level (r = -0.70, P < 0.001 and r = -0.62, P < 0.001, respectively). In contrast, the change of RVEF and SVI was not correlated with the IL-8 level. Esophagectomy is associated with transient depression of myocardial function. IL-6 may contribute to this postoperative myocardial dysfunction. IMPLICATIONS: We examined the association between myocardial function and proinflammatory cytokines after esophagectomy. Interleukin-6 may be the cytokine that most sensitively reflects the postoperative myocardial dysfunction.

Carcinoma, Squamous Cell↗
PubMed2000

MYB-related transcription factor NtMYB2 induced by wounding and elicitors is a regulator of the tobacco retrotransposon Tto1 and defense-related genes.

Transposition of the tobacco retrotransposon Tto1 is regulated mainly by transcription from the long terminal repeat (LTR). Functional analysis of the LTR showed that the 13-bp motif is a cis-regulatory element involved in activation by tissue culture, wounding, and treatment with elicitors. The 13-bp motif contains a conserved motif (L box) that has been implicated in the expression of phenylpropanoid synthetic genes in response to defense-related stresses. To gain further insight into the regulatory mechanism of the retrotransposon and defense-related genes, cDNAs encoding four different proteins binding to the 13-bp motif have been isolated and characterized. One protein is identical to the previously reported NtMYB1, the RNA for which is induced by virus infection; the others are also MYB-related factors. One of these factors, NtMYB2, was analyzed in detail. NtMYB2 mRNA was induced by wounding and by treatment with elicitors. NtMYB2 activated expression from the promoter with the 13-bp motif and from the promoter of the phenylalanine ammonia lyase gene (Pv-PAL2) in tobacco protoplasts. Overexpression of NtMYB2 cDNA in transgenic tobacco plants induced expression of Tto1 and a PAL gene. Together, these results indicate that NtMYB2 is involved in the stress response of the retrotransposon and defense-related genes.

Amino Acid Sequence↗
PubMed2000

Overexpression of presenilin-2 enhances apoptotic death of cultured cortical neurons.

Presenilin-2 (PS2) is a gene of unknown function linked with some forms of familial Alzheimer's disease. To investigate the biological role of PS2 in neurons, we overexpressed PS2 in primary cortical neurons using recombinant adenoviral vectors. Western blot and immunohistochemical analyses showed enhanced expression of PS2 proteins in infected neurons after infection of recombinant adenoviruses containing the human wild-type or mutant PS2 gene. Neuronal survival was decreased by approximately 30% in cultures infected with adenovirus expressing either wild-type or mutant PS2, as compared with those infected with adenovirus expressing the LacZ gene. Fragmented nuclei were frequently observed in dying neurons. These data suggest that apoptotic death of cultured cortical neurons is enhanced by PS2 overexpression.

Animals↗
PubMed2000

The Rad51 paralog Rad51B promotes homologous recombinational repair.

The highly conserved Saccharomyces cerevisiae Rad51 protein plays a central role in both mitotic and meiotic homologous DNA recombination. Seven members of the Rad51 family have been identified in vertebrate cells, including Rad51, Dmc1, and five Rad51-related proteins referred to as Rad51 paralogs, which share 20 to 30% sequence identity with Rad51. In chicken B lymphocyte DT40 cells, we generated a mutant with RAD51B/RAD51L1, a member of the Rad51 family, knocked out. RAD51B(-/-) cells are viable, although spontaneous chromosomal aberrations kill about 20% of the cells in each cell cycle. Rad51B deficiency impairs homologous recombinational repair (HRR), as measured by targeted integration, sister chromatid exchange, and intragenic recombination at the immunoglobulin locus. RAD51B(-/-) cells are quite sensitive to the cross-linking agents cisplatin and mitomycin C and mildly sensitive to gamma-rays. The formation of damage-induced Rad51 nuclear foci is much reduced in RAD51B(-/-) cells, suggesting that Rad51B promotes the assembly of Rad51 nucleoprotein filaments during HRR. These findings show that Rad51B is important for repairing various types of DNA lesions and maintaining chromosome integrity.

Amino Acid Sequence↗
PubMed2000

Cardiac ankyrin repeat protein is a novel marker of cardiac hypertrophy: role of M-CAT element within the promoter.

CARP, a cardiac doxorubicin (adriamycin)-responsive protein, has been identified as a nuclear protein whose expression is downregulated in response to doxorubicin. In the present study, we tested the hypothesis that CARP serves as a reliable genetic marker of cardiac hypertrophy in vivo and in vitro. CARP expression was markedly increased in 3 distinct models of cardiac hypertrophy in rats: constriction of abdominal aorta, spontaneously hypertensive rats, and Dahl salt-sensitive rats. In addition, we found that CARP mRNA levels correlate very strongly with the brain natriuretic peptide mRNA levels in Dahl rats. Transient transfection assays into primary cultures of neonatal rat cardiac myocytes indicate that transcription from the CARP and brain natriuretic peptide promoters is stimulated by overexpression of p38 and Rac1, components of the stress-activated mitogen-activated protein kinase pathways. Mutation analysis and electrophoretic mobility shift assays indicated that the M-CAT element can serve as a binding site for nuclear factors, and this element is important for the induction of CARP promoter activity by p38 and Rac1. Thus, our data suggest that M-CAT element is responsible for the regulation of the CARP gene in response to the activation of stress-responsive mitogen-activated protein kinase pathways. Moreover, given that activation of these pathways is associated with cardiac hypertrophy, we propose that CARP represents a novel genetic marker of cardiac hypertrophy.

Animals↗
PubMed2000

alpha,alpha-gem-Difluorination of alpha-(alkylthio)acetophenone derivatives with N-fluoropyridinium salts.

The alpha,alpha-gem-difluorination of 2',4'-difluoro-alpha-(methylthio)acetophenone (1a) with N-fluoropyridinium salts gave 2',4',alpha,alpha-tetrafluoro-alpha-(methylthio)acetophenone (3a). This reaction was accelerated by the addition of zinc chloride, zinc bromide or anhydrous iron(III) chloride, and higher yields than the reaction without additives were obtained. The gem-difluorination reaction using FP-T300 in the presence of zinc bromide was applicable to other alpha-(alkylthio)acetophenone derivatives (1).

Acetophenones↗
PubMed2000

Effects of rifampin on the glutathione depletion and cytochrome c reduction by acetaminophen reactive metabolites in an in vitro P450 enzyme system.

The present study examined whether rifampin attenuated glutathione (GSH) depletion by acetaminophen reactive metabolites generated in the in vitro P450 enzyme system prepared from mouse liver and the possible mechanism involved in this effect. The results showed that GSH concentration was decreased concentration-dependently by acetaminophen in the in vitro P450 enzyme system. Rifampin significantly attenuated acetaminophen-mediated GSH depletion in a concentration-dependent manner. The concentration-response curve for GSH depletion of acetaminophen was shifted to the right in a parallel fashion in the presence of rifampin at the concentration of 3.2 x 10(-5) M, which appeared to result from the competitive binding of rifampin to acetaminophen metabolites. Cytochrome c was markedly reduced by acetaminophen metabolites in this enzyme system, and GSH concentration-dependently increased the cytochrome c reduction by acetaminophen metabolites. These findings suggested that cytochrome c was reduced by the GSH conjugate of acetaminophen metabolites rather than by acetaminophen-derived superoxide anion (O2*-) and other unbound free radicals. Rifampin was shown to possess an effect similar to that of GSH. It is concluded that the decrease in GSH depletion by rifampin is most likely attributable to the binding of rifampin to the acetaminophen toxic species, and the increase in cytochrome c reduction by rifampin is attributable to the conjugate formed between rifampin and acetaminophen metabolites.

Acetaminophen↗
PubMed2000

The effect of oral clonidine premedication on lumbar cerebrospinal fluid pressure in humans.

Alpha-2 adrenergic agonists including clonidine decrease cerebral blood flow. The specific actions of clonidine on cerebrospinal fluid (CSF) pressure in humans remain to be elucidated. We evaluated the effect of oral clonidine premedication on lumbar CSF pressure in patients without intracranial disease. Seventy-four patients undergoing subarachnoidal block were divided randomly into either a clonidine or a control group. In the clonidine group, the patients were premedicated orally with 5 microg/kg clonidine 60 min before arrival in the operating room. Subarachnoidal puncture was performed via midline approach using a 23-gauge needle at the L2-3 or L3-4 intervertebral space with the patient in the lateral decubitus position. Before the injection of local anesthetic, lumbar CSF pressure was measured. Lumbar CSF pressure was 8.1+/-2.4 mmHg in the clonidine group, which was significantly lower than that in the control group (9.4+/-2.8 mmHg, p<0.05). The cerebral perfusion pressures were 76.2+/-12.5 mmHg in the clonidine group and 91.7+/- 15.4 mmHg in the control group (p<0.001). In the clonidine group, preanesthetic mean blood pressure had a significant correlation with lumbar CSF pressure (r=0.619, p=0.019). We conclude that Lumbar CSF pressure was attenuated by oral premedication with 5 microg/kg clonidine. Clonidine also contributed to a significant correlation between preanesthetic mean blood pressure and CSF pressure.

Administration, Oral↗
PubMed2000

Urinary excretions of albumin and type IV collagen in normotensive and hypertensive subjects.

Plasma albumin leaks into urine as a result of glomerular hypertension and basement membrane injury, while urinary type IV collagen derives from mesangial matrix and glomerular basement membrane. The purpose of this study was to elucidate the pathophysiological significance of these urinary microproteins as an indicator of cardiovascular organ injuries in hypertension. In health-checkup participants without diabetes, proteinuria, or microhematuria, and who were not being treated for hypertension or any other disease at the time of enrollment, urinary albumin and type IV collagen were measured and their relations to organ injuries and cardiovascular risk factors were evaluated. Of 1,079 subjects (40- to 65-year-old; 256 men and 823 women) enrolled in the study, 120 (11.1%) had untreated hypertension exceeding 140/90 mmHg. Urinary albumin was positively correlated with both age (r=0.16, p<0.001) and systolic blood pressure (r=0.27, p<0.001). Urinary type IV collagen was not only positively correlated with age (r=0.12, p<0.001) and diastolic blood pressure (r=0.14, p<0.001) but also negatively correlated with blood hemoglobin (r=-0.12, p<0.001). Urinary albumin, but not type IV collagen, had a significant relation to electrocardiographic signs of left ventricular hypertrophy (p=0.012) and retinal arteriosclerosis on fundoscopy (p <0.001). Thus both albumin and type IV collagen would seem to have increased in association with age and hypertension in this cohort. It is suggested that urinary albumin is an indicator not only of renal injury, but also possibly of development of cardiac hypertrophy and arteriosclerotic changes. Urinary type IV collagen, on the other hand, may be associated with renal tissue injuries that affect erythrokinetics.

Adult↗