Search PubMed⌕ Search

Biomedical subjects

H Adachi

Publications and source records attributed to H Adachi.

At least 307 records · Page 17Linked to original sources

Effects of E4080, a novel bradycardic agent with a coronary vasodilating property, on coronary and systemic hemodynamics in conscious dogs.

The effects of E4080 ((E)-N-[3-((N'-(2-(3,5-dimethoxyphenyl)-ethyl)-N'- methyl)amino)propyl]-4-(4-(1H-imidazol-1-yl)-phenyl)-3-butenamide dihydrochloride dihydrate), a novel bradycardic agent with a coronary vasodilating property, on coronary and systemic hemodynamics were compared with those of pinacidil and nifedipine in chronically instrumented conscious dogs. A pair of piezoelectric crystals and an electromagnetic flow probe were placed on the left circumflex coronary artery. Intravenous infusions of 30, 100 and 300 micrograms/kg/min of E4080 at 30-min intervals to six conscious dogs increased coronary blood flow and decreased total coronary resistance in a dose-dependent fashion, whereas coronary diameter tended to be increased. Although E4080 at a rate of 300 micrograms/kg/min decreased maximally mean aortic pressure by 27 +/- 3% (n = 6, P < .05 vs. base-line value), there was no significant change in the maximal rate of rise in left ventricular pressure or heart rate. Both pinacidil (3, 10 and 30 micrograms/kg/min) and nifedipine (1, 3 and 10 micrograms/kg/min) also tended to increase coronary diameter, and caused an increase in coronary blood flow and decreases in mean aortic pressure and total coronary resistance. In contrast to E4080, however, these changes caused by pinacidil and nifedipine were accompanied by a marked increase in heart rate. All of the drugs tested produced a significant and dose-dependent increase in plasma noradrenaline level. It is concluded that E4080 produces coronary and peripheral vasodilation, without inducing a reflex tachycardia despite sympathetic neural activation. These results suggest that E4080 exerts actions on the cardiovascular system which may be useful in the treatment of angina pectoris.

Animals↗

Evaluation of the pulsatility of a new pulsatile left ventricular assist device--the integrated cardioassist catheter--in dogs.

A new pulsatile left ventricle-femoral artery bypass system (integrated cardioassist catheter system) has been developed for rapid, percutaneous insertion as a left ventricular assist device. Previous experiments revealed its superiority over the intraaortic balloon pump system in maintaining the peripheral circulation and in improving myocardial blood flow and afterload. Our objective was to determine whether the pulsatility of left ventricular bypass of this system would be preferable for maintaining the peripheral circulation and managing the ischemic myocardium as compared with nonpulsatile left ventricular bypass. Ten dogs with profound heart failure were supported by this system. Their hemodynamic status and myocardial blood flow were measured under control, nonpulsatile left ventricular bypass, or synchronous pulsatile left ventricular bypass. Significant differences between the nonpulsatile bypass group and the pulsatile bypass group were observed in the mean increase in aortic pressure (3.5% versus 22.2%, respectively; p < 0.001), total cardiac output (13.0% versus 21.7%; p = 0.004), and myocardial blood flow (9.5% versus 21.8%; p < 0.001). No differences were found between groups in the decrease in left atrial pressure (-20.2% versus -20.2%; p > 0.05). The ratio of diastolic time index/tension time index was shown to be improved significantly in the pulsatile bypass group compared with that of control and nonpulsatile bypass groups (p < 0.001). Thus, the pulsatility of the integrated cardioassist catheter system may support the peripheral circulation and improve the myocardial blood flow and oxygen supply/demand ratio.

Animals↗

[Application of PCPS (percutaneous cardiopulmonary support) to the resuscitation of DOA (dead on arrival) patients].

We report three cases of DOA patients who were resuscitated by using PCPS. All had resisted standard advanced life support methods. The conditions responsible for the heart arrest were acute myocardial infarction (AM1) in 2 (case 1 and 3) and subarachnoid hemorrhage (SAH) in the other (case 2). All 3 were resuscitated by PCPS. Case 1 survived with a slight neurological deficit. Case 2 succumbed to SAH 3 days later. Case 3 was transferred to left heart bypass but succumbed to hemorrhagic infarction of the brain 6 days later. Although this system allows rapid and simple deployment and provides a benefit in resuscitation of DOA patients in a state that is refractory to standard cardiopulmonary resuscitation, the problem of indication for resuscitation remains to be solved.

Angioplasty, Balloon, Coronary↗

Molecular cloning of a cDNA encoding an inducible calmodulin-dependent nitric-oxide synthase from rat liver and its expression in COS 1 cells.

Calmodulin-dependent nitric-oxide synthase, with an apparent molecular mass of 125 kDa, was induced in the liver of rats treated with Propionibacterium acnes and Escherichia coli lipopolysaccharide. Clones were isolated from a cDNA library obtained from induced rat liver using oligonucleotide probes which were synthesized based on the amino acid sequences of peptides of the purified enzyme. Four overlapping cDNA clones for a 3.8-kbp region were isolated and the nucleotide sequences were determined. These clones encompassed an open-reading frame of 3441 bases encoding 1147 amino acids. The deduced amino acid sequence of the cDNA suggested that the protein contains binding sites for NADPH, FAD and FMN. The structure of the possible calmodulin-binding site, consisting of a strongly hydrophobic region surrounded by basic amino acids, is present. The full-length cDNA was expressed in COS 1 cells under the control of a cytomegalovirus promoter and the expressed enzyme was found to be a calmodulin-dependent nitric-oxide synthase. A structural comparison suggested that the liver nitric-oxide synthase is the same as the macrophage enzyme. Northern-blot analysis showed that the mRNA in the liver is approximately 4.2 kb long and is induced transcriptionally by treatment with P. acnes and lipopolysaccharide.

Amino Acid Oxidoreductases↗

Importance of Glu-125 in the catalytic activity of human renal dipeptidase.

The carboxyl reagent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) and dansyl-ethylenediamine have shown to inhibit human renal dipeptidase (hrDP) irreversibly in a time-dependent manner. Cilastatin, a competitive inhibitor of the enzyme, partially protected the enzyme from inactivation. To identify the site(s) modified by EEDQ and dansylethylenediamine, the amino-acid sequence of tryptic fragments of modified enzyme were analyzed extensively. A comparison of the determined amino-acid sequences with the predicted primary structure of hrDP revealed that Glu-125 within the Glu115-Arg138 fragment was modified. In consequence, the role of Glu-125 in catalytic activity was investigated by site-directed mutagenesis. Glu-125 was replaced by a glutamine, aspartic acid or cysteine residue. cDNAs for wild-type or mutated enzymes were expressed in CHO cells, and the resulting proteins were purified to apparent homogeneity. The mutated enzyme, Gln-125-hrDP exhibited specific activity of 28.5 U/mg, corresponding to 11.4% of the wild-type. In contrast, Asp-125-hrDP and Cys-125hrDP were found to be inactive (< or = 0.1% of wild-type enzyme). These results suggest that the polarity and/or length of the side chain of Glu-125 residue are important for the enzyme activity.

Amino Acid Sequence↗

The effects of walking at the anaerobic threshold level on vertebral bone loss in postmenopausal women.

The purpose of this study was to determine the optimal intensity of exercise necessary to prevent the postmenopausal bone loss on the basis of anaerobic threshold (AT). Thirty-three postmenopausal women were randomized to control (group C: n = 12) or two exercise groups (group H and group M). All women performed a treadmill exercise test, and the AT was measured by expired gas analysis. The exercise regimen consisted mainly of walking at a speed that kept the exercise heart rate above the AT (group H: n = 12) or below the AT (group M: n = 9). Exercise was performed for 30 minutes, three times a week for 7 months. The bone mineral density (BMD) of the lumbar vertebrae was measured using dual energy X-ray absorptiometry. The BMD level in group C decreased by 1.7 +/- 2.7%, but there was a significant increase of 1.1 +/- 2.9% in group H. In group M there was a decrease of 1.0 +/- 3.1% which did not differ from group C. In group C, serum osteocalcin and urinary hydroxyproline excretion were significantly increased, but no changes were seen in either of the exercise groups. Urinary calcium significantly decreased in the exercise groups. We conclude that short-term (7 months) exercise with intensity above the AT is safe and effective in preventing postmenopausal bone loss.

Absorptiometry, Photon↗

Serum and gastric mucosal pepsinogens in atrophic gastritis, particularly in type A gastritis associated with pernicious anemia in Japanese.

The levels of serum pepsinogen I (PG I) and pepsinogen II (PG II) were determined by IRMA (immunoradiometric assay) and the ratio of PG I/II calculated in 37 patients with type A gastritis and concomitant pernicious anemia (PA) and in 97 with chronic gastritis (type B gastritis) among Japanese. In several patients from each group, PG I and PG II in the gastric mucosa were stained by an enzyme antibody assay to compare the percentage of positively stained cells with levels of serum PG I and PG II. The levels of serum PG I and PG II in chronic gastritis decreased as the degree of atrophy increased. Serum PG I and PG II levels in PA were lower than those of patients with severe atrophy. Most of serum PG I levels in PA were less than 10 ng/ml. The PG I/II ratio also decreased as the severity of atrophy increased, distinctly showing that in PA, the ratio were quite low and most of them are less than 1.0. Gastric mucosal pepsinogen showed a tendency similar to that of serum levels and also refrected the degree of atrophy. Therefore, by measuring these parameters it should be easier to determine the extent of atrophy, and to establish a serological diagnosis of type A gastritis associated with PA.

Anemia, Pernicious↗

Short-term effects of denopamine on anaerobic threshold and related parameters in patients with chronic heart failure: a double-blind crossover study.

BACKGROUND: The short-term effects of denopamine, an orally available beta-stimulant, on exercise capacity were studied in patients with chronic heart failure. METHODS AND RESULTS: Nineteen patients entered the study. Three patients had ischemic heart disease, 13 had dilated cardiomyopathy, and three had valvular disease; 16 patients were in New York Heart Association class II, and three patients were in New York Heart Association class III. Symptom-limited exercise testing (ramp protocol) on a bicycle ergometer with gas exchange analysis was conducted 1 hour after oral administration of either 20 mg denopamine or placebo. Drug administration sequence was randomly assigned in a double-blind crossover method, with 1 week between drugs. Peak VO2 was 20.4 +/- 3.2 and 21.2 +/- 3.1 ml/min/kg, respectively, for those administered the placebo and the drug, and anaerobic threshold was 13.1 +/- 2.1 and 14.0 +/- 2.0 ml/min/kg. There was a significant increase in peak VO2 (p < 0.05) and anaerobic threshold (p < 0.01) with denopamine, whereas no significant change was observed in peak work rate or exercise time. Denopamine increased heart rate in patients with atrial fibrillation but had little effect on heart rate in patients with sinus rhythm. CONCLUSION: Data obtained from gas exchange analysis are more sensitive and potentially more useful in the detection of short-term changes in exercise capacity than data obtained from either exercise time or peak work rate, indexes that are commonly used to assess drug therapy. Patients with mild-to-moderate heart failure with sinus rhythm, but not those with atrial fibrillation because of its frequent induction of tachycardia, may be good candidates for denopamine therapy.

Adrenergic beta-Agonists↗

Involvement of epidermal growth factor in inducing obesity in ovariectomized mice.

Ovariectomy (Ovx) of mice significantly increases the epidermal growth factor (EGF) concentration in the submandibular gland. To elucidate the role of this elevated EGF in obesity of Ovx mice, we examined the effects of sialoadenectomy (Sx) and anti-EGF rabbit antiserum administration on the body weight (BW) gain and carcass fat deposition in Ovx animals. Studies were performed in four groups of mice consisting of control, Ovx, Ovx+Sx, and Ovx+anti-EGF groups. Ovx increased the BW gain compared with the control animals, whereas Sx and anti-EGF significantly reduced it. Although the relative weights (weight ratio to BW) of the liver and kidney were not significantly changed by Ovx, Sx, or anti-EGF treatment of Ovx mice, the relative weights of mesenteric, parametrial, and subcutaneous fat tissues were increased in Ovx mice, and this increase was significantly reduced by Sx or anti-EGF administration. Ovx induced adipocyte hypertrophy, and this effect was eliminated by Sx and anti-EGF. Moreover, acyl-CoA synthetase mRNA level was increased by Ovx, and this increase was reduced by Sx and anti-EGF in mesenteric fat tissue. These findings suggest that elevation of EGF may play a role in the induction of obesity in Ovx mice.

Acetate-CoA Ligase↗

Menstrual stage-specific expression of epidermal growth factor and transforming growth factor-alpha in human oviduct epithelium and their role in early embryogenesis.

We studied the expression of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha in human oviduct epithelium at various menstrual stages. Immunohistochemical stainings using anti-EGF and anti-TGF alpha antibodies showed a specific staining in ampullary oviduct epithelium at late follicular and luteal stages, but the stainings were very weak at early follicular stage. Quantitative reverse transcription and polymerase chain reaction, using beta-actin messenger RNA as an internal standard, revealed the menstrual stage-specific expression of EGF and TGF alpha gene transcripts: relative amounts of EGF and TGF alpha messenger RNA to those of beta-actin were 1.5 +/- 1.9% (mean +/- SD) and 1.4 +/- 0.6% (n = 3) at early follicular, 16.5 +/- 4.9% and 12.6 +/- 2.6% (n = 3) at late follicular, and 18.9 +/- 2.2% and 13.8 +/- 3.2% (n = 3) at luteal stages, respectively. The expression of these growth factors was in proportion to the increase in serum estradiol but not to progesterone levels. To clarify the biological significance of these growth factors, mouse two-cell embryos were cocultured with human oviduct epithelial cells with or without blocking the action of these growth factors. Cocultures significantly promoted blastocyst formation, but this promotive effect of the oviduct epithelial cells was completely abolished by the addition of anti-EGF and/or anti-TGF alpha monoclonal neutralizing antibodies to the coculture system. All these results showed that EGF and TGF alpha were synthesized and expressed in human oviduct epithelium specifically to menstrual stages, and that these growth factors may be involved in early embryonic development.

Actins↗

Studies on zoospore attracting activity. II. Synthesis of isoflavones and their attracting activity to Aphanomyces euteiches zoospore.

Nineteen isoflavones were synthesized and their attracting activity to Aphanomyces euteiches zoospore were investigated. Isoflavones (1, 2, 4, 16 and 19) with an unsubstituted B ring were synthesized by the oxidation of corresponding 2'-hydroxychalcones with thallium (III) nitrate trihydrate in methanolic perchloric acid. A hydroxyl group at the C-5 position in isoflavones was necessary for strong attraction to A. euteiches zoospore. The introduction of an additional hydroxyl group at the C-7 or C-4' position strengthened the attracting activity. Moreover, the methylation of the C-7 hydroxyl group strengthened the attracting activity, but the methylation of the C-4' hydroxyl group slightly weakened it. The naturally occurring isoflavones (9 and 10), which were reported to possess estrogen activity, showed moderate attracting activity.

Chalcone↗

Inhibitory effects of tannins on NADH dehydrogenases of various organisms.

We examined the effects of purified tannins and related compounds (33 species) on NADH-ubiquinone-1 oxidoreductase activity in four kinds of organism (Paracoccus denitrificans, Bacillus subtilis, Photobacterium phosphoreum, and Thermus thermophilus HB-8) and rat liver mitochondria. In addition to pentagalloylglucose, which was reported as a potent inhibitor of NADH dehydrogenases (NDH), sanguiin H-11, oolonghomobisflavan A, and polymerized procyanidin are potent inhibitors for both types of NDH (NDH-1 and NDH-2). We found that some other tannins contained in tea are also inhibitors of NDH from all organisms.

Animals↗

Nitric oxide synthase mRNA in endothelial cells: synergistic induction by interferon-gamma, tumor necrosis factor-alpha and lipopolysaccharide and inhibition by dexamethasone.

Regulation of nitric oxide synthase mRNA by interferon-gamma, tumor necrosis factor-alpha, bacterial lipopolysaccharide (LPS) and dexamethasone in rat aortic endothelial cells was examined. The combination of interferon-gamma (100 U/ml) and tumor necrosis factor-alpha (5000 U/ml) evoked a time-dependent increase in nitric oxide synthase mRNA and nitrite/nitrate production, both of which were inhibited by dexamethasone. Neither interferon-gamma (100 U/ml), tumor necrosis factor-alpha (5000 U/ml) nor LPS (100 ng/ml) alone was capable of increasing nitric oxide synthase mRNA and nitrite/nitrate production in these cells. However, combinations of two of the three agents synergistically increased both nitric oxide synthase mRNA and nitrite/nitrate production. When the three agents were applied simultaneously, nitric oxide synthase mRNA and nitrite/nitrate production were both markedly increased. LPS contamination, which may affect the induction of nitric oxide synthase, was below 20 pg/ml in all experiments unless LPS was added exogenously, namely, the effects observed were those of the cytokines themselves. Our results suggest that in endothelial cells, these cytokines regulate the production of nitric oxide at the level of nitric oxide synthase mRNA induction.

Amino Acid Oxidoreductases↗

Dexamethasone inhibits nitric oxide synthase mRNA induction by interleukin-1 alpha and tumor necrosis factor-alpha in vascular smooth muscle cells.

The effects of interleukin-1 alpha, tumor necrosis factor-alpha and dexamethasone on the induction of nitric oxide synthase mRNA in rat aortic smooth muscle cells were studied. Neither interleukin-1 alpha (up to 100 U/ml) nor tumor necrosis factor-alpha (up to 5000 U/ml) was capable of inducing nitrite/nitrate production and nitric oxide synthase mRNA in smooth muscle cells. In contrast, treatment for 12 hr or longer with a combination of the two synergistically induced nitrite/nitrate and cyclic GMP production in cell culture media and nitric oxide synthase mRNA, both of which were prevented by dexamethasone. Contamination with bacterial lipopolysaccharide, which may affect the induction of nitric oxide synthase, was below 30 pg/ml in all experiments. Our findings show that dexamethasone and these cytokines regulate the induction of nitric oxide synthase at the mRNA level in vascular smooth muscle cells.

Amino Acid Oxidoreductases↗

[Post-sternotomy mediastinitis treated by omental transposition].

Mediastinitis after cardiac surgery is a serious complication with high morbidity and mortality rates. Between December 1989 and April 1992, of 264 patients who underwent cardiac or aortic surgery with median sternotomy, seven (2.6%) developed deep sternal infections with mediastinitis. Six of these patients were treated with debridement, irrigation and delayed wound closure with mediastinal transposition of the greater omentum. Most of the infections were associated with several predisposing factors: cardiac cachexia in the preoperative state, prolonged perfusion time, and respiratory insufficiency in the postoperative period. One of the six patients died of adult respiratory distress syndrome in the postoperative course, but the remaining five patients were discharged with their wounds well healed. Acute and deep mediastinal infection occurred in one patient on the fifth day after cardiac surgery. The infection was successfully treated with radical debridement, two days of intermittent mediastinal irrigation and staged wound closure with omental transposition into the mediastinum. The omental transfer was achieved as follows: after the greater omentum was divided into two pedicles one pedicle was used to fill in the pericardial space and the other was placed between the sternum and the undermined skin. We conclude that early debridement and omental flap transposition are effective in the management of mediastinitis after cardiac surgery.

Aged↗

[Preoperative evaluation of a distal aortic arch aneurysm by spiral CT with three-dimensional reconstruction].

Sixty-seven-year-old male with a distal aortic arch aneurysm was evaluated by spiral CT with three-dimensional reconstruction. Spiral CT allows rapid data acquisition through an entire anatomic region during a single breath hold. The helically acquired data undergo interpolation. Transverse images are reconstructed with slice intervals 1-4 mm apart. Three-dimensional images were generated by these data with the transverse images. The entire anatomical correlation with the aneurysm and the aortic arch branches was clearly recognized by these three-dimensional images. Preoperative evaluation of the distal aortic arch aneurysm by spiral CT with three-dimensional reconstruction was useful for the surgical treatment.

Aged↗

[Surgical treatment of adult secundum ASD with severe pulmonary hypertension--two case reports].

Indication and treatment of adult secundum ASD with severe PH was discussed in two surgical cases. Case 1: 32-year-old woman with dyspnea on exercise. After 100% O2 inhalation, PA systolic pressure changed from 103 to 104 mmHg, left to right shunt ratio changed from 18.2% to 52.2%, Qp/Qs changed from 1.07 to 2.08, Rp/Rs changed from 0.58 to 0.28, PVR changed from 1606 to 805 dyne.sec.cm-5 respectively. Because the reversibility of pulmonary obstructive disease was recognized, ASD closure was performed. Her activity became well, and PVR was decreased to 758 after the operation. Case 2: 63-year-old man with dyspnea on exercise. After 100% O2 inhalation, PA systolic pressure changed from 102 to 95 mmHg, Left to right shunt ratio changed 31.9 to 51.0%, Qp/Qs changed from 1.30 to 2.0, Rp/Rs changed from 0.65 to 0.39, PVR changed from 1257 to 806 dyne.sec.cm-5. After the operation, he got well, and PA systolic pressure was decreased to 85 mmHg, PVR was 620. 100% O2 inhalation test was valuable to evaluate the reversibility of pulmonary obstructive state and to decide the surgical indication.

Adult↗

[Selective cerebral perfusion with cold blood for the surgical treatment of aortic arch aneurysm].

To determine whether the selective cerebral perfusion with cold blood is useful for repair of aortic arch aneurysm, 7 consecutive patients with aneurysms were examined (October, 1991-July, 1992). Four of 7 patients (57%) required emergency surgery due to the aortic rupture. Surgical repair was performed under the moderate core hypothermia (20-25 degrees C) to avoid prolonged cardio-pulmonary bypass (CPB), and the selective cerebral perfusion with oxygenated cold blood (16 degrees C, 350-450 ml/min) was employed for cerebral protection. The selective cerebral perfusion system was easily added to the ordinary CPB system with low priming volume (150 ml). The mean cerebral perfusion time, the mean cardiac arrest time, and the mean CPB time in this series were 93 min, 93 min, and 201 min, respectively. One of 7 surgical cases (14%) died due to the postoperative complication (multiple organ failure). Other 6 patients recovered and discharged. Successful cerebral protection and avoidance of prolonged CPB may be achieved by this unique method. The selective cerebral perfusion with cold blood may be one of the useful and reliable methods for repair of aortic arch aneurysm.

Adult↗