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Biomedical subjects

E Sugimoto

Publications and source records attributed to E Sugimoto.

At least 37 records · Page 2Linked to original sources

Effects of recombinant human soluble thrombomodulin (rhs-TM) on clot-induced coagulation in human plasma.

Recent studies have suggested that clot-bound thrombin plays an important role in thrombus growth. In this study, we examined the effects of recombinant human soluble thrombomodulin (rhsTM) on clot-induced coagulation. rhsTM enhanced the activation of protein C by clots, and attenuated clot-induced thrombin generation and fibrinopeptide A (FPA) production in a dose-dependent manner. The inhibitory effect of rhsTM was abolished by anti-protein C antibody. The inhibitory effect of rhsTM on clot-induced thrombin generation continued for over 60 min after the addition of the clot, while an active site-directed thrombin inhibitor, argatroban, produced a more transient inhibition. rhsTM also inhibited the regrowth of the clot in (125)I-fibrinogen-supplemented plasma. We also examined the effect of rhsTM by thromboelastography, rhsTM reduced the growth of the clot but had little effect on the time to begin clotting, while heparin and Fragmin (low molecular weight heparin) had effects opposite to those of rhsTM. These findings suggest that rhs-TM attenuates the growth of the clot by activating protein C and inhibiting further thrombin generation in the clot.

Antithrombins↗

Expression of the putative membrane fatty acid transporter (FAT) in taste buds of the circumvallate papillae in rats.

The putative membrane fatty acid transporter (FAT) protein and its mRNA, originally expressed in adipose tissue, were found in the tongue of rats. Northern blot analysis showed a significant expression of FAT mRNA in the epithelial layer of circumvallate papillae. Immunohistochemical staining revealed that immunoreactivity for FAT is specifically localized in the apical part of taste bud cells, possibly gustatory cells, in the circumvallate papillae.

Animals↗

High-performance liquid chromatographic measurement of urocanic acid isomers and their ratios in naturally light-exposed skin and naturally shielded skin.

We have developed methods for sampling and extraction of trans-urocanic acid and cis-urocanic acid from human skin, and subsequent high-performance liquid chromatographic measurement of these isomers. Sampling involves applying cellophane adhesive tape to the skin for 10 s. Urocanic acid isomers were completely extracted by immersing the tape in KOH solution. The HPLC column was a Tosoh ODS 80TS (250x4.6 mm I.D., 7 microm average particle size) eluted with 20 mM potassium dihydrogenphosphate containing 1 g/l sodium heptanesulphonate (pH 3.7)-acetonitrile (93:7, v/v) at a flow-rate of 1.0 ml/min. The isomers were detected by UV absorbance at 264 nm. This technique was used to analyze the ratio of trans-urocanic acid/cis-urocanic acid on human skin at various sites on the body. It was found that the ratio was low in naturally light-exposed skin and high in naturally shielded skin.

Adult↗

Long-term consumption of an amino acid diet reduces the pancreatic enzyme secretion response to a trypsin inhibitor in rats.

We investigated pancreatic enzyme secretion in response to soybean trypsin inhibitor (SBTI) in rats fed amino acids as a nitrogen source, from the fetal stage to adulthood. Pregnant rats were divided into two groups 4 d before parturition. During gestation and nursing, one group was fed a 15% protein diet (protein-fed rats) and the other (amino acid-fed rats) a 15% amino acid mixture diet that simulated the composition of the protein diet. Each male offspring was weaned at 4 wk after parturition and fed the same diet as fed to its dam for an additional 6 wk. Pancreatic amylase secretion in response to an intraduodenal infusion of SBTI (10 mg/rat) was observed in the protein-fed rats but not in the amino acid-fed rats. Amylase secretion in response to an intravenous injection of cholecystokinin (CCK) (10 ng/kg rat) was observed in both groups, and the magnitude of the response was significantly higher in the amino acid-fed rats than in the protein-fed rats. An increase in the level of plasma CCK in response to SBTI was observed in the protein-fed rats but not in the amino acid-fed rats. These results suggest that the long-term amino acid diet, because of its ability to inhibit the SBTI-stimulated CCK-releasing process in the small intestine of rats, reduced the pancreatic enzyme secretion response to a trypsin inhibitor. Six rats fed the amino acid mixture until 1 wk after weaning were fed the protein diet for the next 5 wk. These rats showed no pancreatic amylase secretion in response to SBTI, suggesting that dietary components around the weaning stage may affect the development of the ability of small intestinal cells to recognize a trypsin inhibitor.

Amino Acids↗

Mechanisms of CCK regulation of monitor peptide mRNA expression in pancreatic acinar AR42J cells.

We explored the mechanism(s) by which cholecystokinin (CCK) stimulation of AR42J rat pancreatoma cells results in increased mRNA expression of a CCK-releasing peptide [monitor peptide (MP)]. With the use of a newly established reverse transcription-polymerase chain reaction assay system, CCK was shown to increase the level of MP mRNA by about ninefold. When protein synthesis was blocked by addition of cycloheximide, the MP mRNA level remained unchanged in the presence of CCK. Inhibition of transcription with actinomycin D resulted in a half-life for MP mRNA of approximately 17 h, and this rate remained unchanged after CCK treatment, suggesting that CCK may regulate the MP mRNA level by influencing gene transcription. A-23187, bombesin, substance P, and carbachol increased the MP mRNA level. CoCl(2) abolished actions of both CCK and A-23187 on MP mRNA expression. Dibutyryl-adenosine 3',5'-cyclic monophosphate, forskolin, secretin, and vasoactive intestinal polypeptide had no effect on MP mRNA expression. 12-O-tetradecanoylphorbol-13-acetate and phorbol 12,13-dibutyrate also failed to increase MP mRNA. It was therefore proposed that CCK stimulates MP mRNA expression of AR42J cells in a Ca2+-dependent and protein kinase C-independent manner.

Animals↗

[A case of porencephaly with mirror movements: pathophysiological investigation by using long-latency long-loop reflex and dipole tracing method].

We report a 42-year-old left-handed woman with congenital right hemiparesis and bilateral mirror movements in the hands. She had a porencephaly of the left hemisphere and the brain MRI demonstrated cortical and subcortical defect of the left hemisphere from Brodmann's area 6 to 40 including the left motor cortex. By electrical stimulation of the left median nerve at the wrist, N20 of the somatosensory evoked potential was recorded in the right postcentral gyrus by using the dipole tracing method. Long-loop reflexes from the bilateral thenar muscles were recorded and their latencies were almost the same. The stimulation of the right median nerve did not evoke N20, nor long-loop reflex. These electrophysiological findings suggest that the reorganization of the motor system made the right motor cortex to innervate bilateral hands, and caused bilateral mirror movements. In other words, the mirror movements managed to relieve the paralysis of the right hand though the damage of the left motor cortex was present. In the previous literature we are able to find hypotheses regarding the mechanism of mirror movements in congenital hemiparesis. Here we discussed about the reorganization of the motor system in the damaged brain.

Cerebral Cortex↗

Roles of tyrosine kinase in insulin action on cell volume of fetal rat type II pneumocyte.

The aim of the present study was to investigate the roles of tyrosine kinase (TK) in the insulin action on cell volume in fetal rat (20-day gestational age) type II pneumocyte. Insulin (100 nmol/l) increased cell volume, and this insulin (100 nmol/l) action was completely blocked by 50 micromol/l bumetanide (BMT) and 10 micromol/l amiloride (AML). This observation indicates that 100 nmol/l insulin activates BMT-sensitive Na+/K+/2Cl- cotransporter and AML-sensitive pathways. The stimulatory action of 100 nmol/l insulin on BMT-sensitive Na+/K+/2Cl- cotransporter was completely abolished by 10 micromol/l lavendustin A (LAV-A, an inhibitor of TK), however 100 nmol/l insulin could stimulate AML-sensitive pathways even in LAV-A (10 micromol/l)-treated cells. These observations indicate that the insulin (100 nmol/l) action on the BMT-sensitive Na+/K+/2Cl- cotransporter is mediated through TK-dependent pathways, while 100 nmol/l insulin requires a TK-independent pathway to show the stimulatory action on the AML-sensitive pathways. From these observations we conclude that TK-dependent and -independent pathways are involved in the insulin (100 nmol/l) signaling in fetal rat type II pneumocyte.

Amiloride↗

Cloning and nucleotide sequence of ApaLI restriction-modification system from Acetobacter pasteurianus IFO 13753.

The ApaLI restriction-modification system from Acetobacter pasteurianus IFO 13753 recognizes the nucleotide sequence GTGCAC. The gene coding for the ApaLI methylase (M.ApaLI) was cloned into Escherichia coli DH5 alpha MCR, and the nucleotide sequence of the gene was analyzed. The M.ApaLI gene coded for a protein of 429 amino acid residues (molecular mass, 46,554 daltons). The ApaLI restriction endonuclease (R.ApaLI) gene was analyzed by inverse polymerase chain reaction. The R.ApaLI gene coded for a protein of 375 amino acid residues (molecular mass, 42,143 daltons). The two genes had the same orientation separated by two base pairs. The deduced amino acid sequence of M.ApaLI shows significant similarities to the family of cytosine-5 methylases. However, the deduced amino acid sequence of R.ApaLI did not have as much relatedness in the nucleotide sequence, when compared with those of the other restriction endonucleases already reported.

Acetobacter↗

Cloning and nucleotide sequence of the AgeI methylase gene from Agrobacterium gelatinovorum IAM 12617, a marine bacterium.

The AgeI restriction-modification system from a marine bacterium, Agrobacterium gelatinovorum IAM 12617, recognizes the nucleotide sequence ACCGGT. The gene coding for the AgeI methylase (M.AgeI) was cloned into Escherichia coli DH5 alpha MCR, and the nucleotides of the gene were sequenced. The M.AgeI gene coded for a protein of 429 amino acid residues (molecular mass, 47,358 daltons). The deduced amino acid sequence of M.AgeI was compared with those of other methylases and showed that there are high degrees of similarity in some cytosine-5 methylases.

Amino Acid Sequence↗

The possibility of active form of vitamins A and D as suppressors on adipocyte development via ligand-dependent transcriptional regulators.

The study aimed to systematically examine the effects of fat soluble vitamins and their analogs on terminal differentiation of adipocytes on the cellular and molecular aspects. It is well known that fat soluble vitamins especially vitamins A and D inhibit the differentiation of adipocytes in cultured cells. Furthermore, it has been revealed that the low level of dietary fat soluble vitamins, especially vitamin A and carotenoid actively stimulate the development of adipose tissue, namely bovine marbling in vivo. We have shown that the expression of retinoic acid receptor (RAR) alpha and gamma, retinoid X receptor (RXR) alpha and beta, and vitamin D receptor (VDR) mRNA were abundant in rat adipose tissue and 3T3-L1 cells. The autoregulated amplification and reduction of RAR, RXR and VDR mRNA by their own ligands, were observed in 3T3-L1 cells. Finally, we proposed the model of vitamins A and D as suppressors on adipocyte development through retinoid/thyroid/vitamin D/fatty acid-activated/peroxisomal proliferator-activated receptor's subfamily.

3T3 Cells↗

Cloning and sequencing of the gene encoding the mouse vitamin D receptor.

The mouse vitamin D receptor (VDR)-encoding cDNA was cloned and the coding regions were sequenced. Comparison of the amino-acid sequence to that of humans and rats revealed high homology in the DNA- and ligand-binding domains. Divergence appeared in the internal region between the two domains.

Amino Acid Sequence↗

Swimming endurance capacity of mice is increased by chronic consumption of medium-chain triglycerides.

The effect of chronic administration of medium-chain triglycerides (MCT) on swimming endurance (swim capacity) was investigated in male Std ddY mice. The mice were fed a diet containing 80 g MCT + 20 g long-chain triglycerides (LCT)/kg diet for 6 wk; mice fed diet containing 100 g LCT/kg diet were used as controls. After being accustomed to swimming, the mice were subjected to forced swimming every 2 d in the current water pool that we had developed, and the total swimming period until exhaustion was measured. The total swimming period was used as the index of swim capacity. The group fed MCT showed significantly greater swim capacity than the control group (89.5 +/- 2.5 vs. 80.2 +/- 2.0 min). In another experiment, after 4 wk of MCT diet consumption, significantly greater swim capacity was found in untrained mice. The major metabolic consequences of the adaptations of muscle to prolonged MCT administration during endurance training were higher activities of 3-oxo acid CoA-transferase (P < 0.01), citrate synthase (P < 0.1) and malate dehydrogenase (P < 0.1). These findings suggest that increases in the enzyme activities of the tricarboxylic acid cycle and ketone body utilization associated with the chronic administration of an MCT-containing diet enhance swim capacity in mice.

Animals↗

A new compound (AZ36041) promotes the survival of the neurons and reduces neurotoxicity of Alzheimer's beta-amyloid protein.

Alzheimer's beta-amyloid protein (A beta) is the main component of senile plaques, which are characteristic hallmarks of the Alzheimer's disease brain. Recently, there have been several reports that A beta has toxic effects on both cultured neurons and in the brain. We confirmed the neurotoxicity of A beta in vitro and found a new compound, called AZ36041 (4-chloro-N-(5-nitro-2-tiazoyl)benzenesulfone amide), which dramatically reduced A beta neurotoxicity. This compound was also found to have a neuroprotective effect against toxicity of glutamate and enhanced neuronal survival in the absence of neurotoxic compounds. AZ36041 may be a useful tool for investigating the mechanism of A beta neurotoxicity in vitro and in vivo.

Amyloid beta-Peptides↗

Recognition system for dietary fatty acids in the rat small intestine.

Linoleic acid and oleic acid markedly increased the influx of 45Ca into isolated intestinal epithelial cells, and this increase reflected a rise in the intracellular calcium level. Methyl linoleate had no effect, while glutamic acid and somatostatin both inhibited the linoleic acid-induced influx of 45Ca. In addition, methyl linoleate had no effect, while glutamic acid inhibited linoleic acid-induced hormone-responsive pancreatic exocrine secretion.

Animals↗

The recognition system of dietary fatty acids by the rat small intestinal cells.

Small intestinal epithelial cells interact with a rather high concentration of fatty acids derived from the diet. These fatty acids directly or indirectly regulate the functions of the small intestine. We report here that linoleic acid and oleic acid markedly increased the influx of 45Ca2+ into the small intestinal epithelial cell line (IEC 6). By contrast, octanoic acid, methyl linoleate, and linolyl alcohol had no effect on the influx. Acidic amino acids, methyl linoleate, and linolyl alcohol, inhibited the linoleic acid-induced influx of 45Ca2+, indicating that activation of the influx by linoleic acid depended on the chain length and was affected by the presence of a carboxyl group. Of the gastrointestinal hormones, somatostatin specifically inhibited the linoleic acid-induced influx of 45Ca2+.

Amino Acids↗

Midgut carcinoid tumours. CT appearance.

CT was performed on 80 patients referred for staging and treatment of histologically verified midgut carcinoid tumours. In 17 cases (21%) CT was normal in spite of biochemical signs of tumour (increased U-5-HIAA). The most common finding was liver metastases in 54/80 (68%) of patients. Mesenteric metastases, usually as a soft tissue mass at the mesenteric root, were found in 17/80 (21%). Retroperitoneal adenopathy was found in 19/80 (24%). During a follow-up time of 3 months to 10 years (median 3 years) 445 additional CT examinations were performed on 77 patients. In 39 of these, progressive disease (new lesions) was found after a median time of 15 months (range 3 months-6.5 years). CT is poor in detecting primary carcinoid tumours but helpful in evaluating the extent of tumour spread before surgical exploration and during follow-up once the diagnosis has been established.

Adult↗

[Contrast-enhanced 3D MR angiography of the chest and abdomen with breath-holding using phase reordering].

This report presents the feasibility of phase-recordered contrast-enhanced three-dimensional MR angiography in 32 consecutive patients with vascular abnormalities in the chest and abdomen. To suppress motion artifacts due to respiratory corruption, a phase-reordering technique was introduced so that the low frequency components of the phase data were obtained first during the imaging period. Image quality and degree of motion suppression were assessed by four radiologists independently without information on breath-holding time. Abnormalities were detected in 30 cases (93.8%), and their extent was correctly assessed in 28 cases (87.5%). More confident assessment was possible in abnormalities of the pulmonary vessels and thoracic aorta than in those of the abdominal aorta and portal venous system. With phase reordering, more than 20 seconds of breath-holding ensured image quality sufficient to correctly assess the vascular abnormalities. While this technique is easy and requires only single breath-holding, it can provide excellent MRA without slice-to-slice spatial misregistration.

Aortic Aneurysm, Abdominal↗

Androgen receptor antagonist suppresses exercise-induced hypertrophy of skeletal muscle.

The physiological importance of the increase in androgen receptors in exercise-induced muscle hypertrophy was investigated in rats. Together with training rat gastrocnemius muscles by electrical stimulation every other day for 2 weeks, male rats were administered the androgen receptor antagonist, oxendolone. The androgen receptor antagonist effectively decreased the wet mass of the prostate, an androgen target organ, and did not significantly affect body mass. The increase in muscle mass induced by electrical stimulation was effectively suppressed by the androgen receptor blockade. The mean degree of muscle hypertrophy in the antagonist-treated group was significantly lower than that in the control group (102.30% vs 107.41%, respectively; P = 0.006). This result suggests that the androgen pathway has a significant effect in exercise-induced muscle hypertrophy and emphasizes the importance of the increase in the number of androgen receptors in exercised muscle.

Androgen Receptor Antagonists↗