Biomedical subjects

N Akatsuka

Publications and source records attributed to N Akatsuka.

At least 19 recordsLinked to original sources

PubMed2001

Non-essential amino acids play an important role in adaptation of the rat exocrine pancreas to high nitrogen feeding.

We have previously demonstrated that feeding a diet with a high amino acid (60% AA diet) content, as a mixture simulating casein, induced pancreatic growth and pancreatic protease production in rats. In the present study, we examined the effects of an increasing dietary content of essential amino acids (EAA, x1 - x3 in exp. 1 and x1 - x3.3 in exp. 2) and non-essential amino acids (NEAA, x1 - x3 in exp. 1 and x1 - x5.2 in exp. 2) on pancreatic growth, amylase and protease adaptation using casein-type amino acid mixtures (exp. 1, basal diet; 20% AA diet) and egg white-type amino acid mixtures (exp. 2, basal diet; 12% AA diet). Pancreatic growth and trypsin activity were induced as the dietary content of NEAA was increased in experiments 1 and 2. Amylase activity in the pancreas was also induced as the dietary content of NEAA was increased, even with the decrease in dietary carbohydrate in experiment 2. The values of all pancreatic variables decreased with the increase in dietary EAA (x2 and x3) without an increase in NEAA. The changes in the pancreas were coincident with increases in plasma arginine and lysine concentrations and a decrease in the plasma alanine concentration. In rats fed a 60% AA diet (EAA and NEAA x3), in the case of which the EAA content was balanced with the NEAA content, pancreatic growth and protease production increased and reached maximum levels as the plasma amino acid concentrations decreased, except for alanine. These results show that NEAA, not EAA, are associated with induction of pancreatic growth and protease production upon feeding a diet with a high AA content, and that some metabolites may be involved in the induction process. The suppression of pancreatic growth and protease production in rats fed the high EAA diets without balanced NEAA may be associated with impairment of amino acid metabolism rather than the increments in the concentration of one or more essential amino acids. Our results also suggest that there is an unknown mechanism or unknown factors involved in regulating pancreatic amylase.

Journal Article↗

PubMed2000

Induction of pancreatic trypsin by dietary amino acids in rats: four trypsinogen isozymes and cholecystokinin messenger RNA.

We previously demonstrated that feeding a diet containing a high level of amino acid mixture simulating casein (AA) induced an increase in pancreatic protease activities in rats. In the present study, this effect of dietary AA was further characterized with three separate experiments. These experiments (1) examined periodic changes in pancreatic and small intestinal trypsin activities after switching from a 20% (a normal nitrogen level) AA diet to a 60% AA (a high nitrogen level) diet; (2) measured the abundance of mRNA for four trypsinogen isozymes and for intestinal cholecystokinin (CCK) and secretin in rats fed 20% and 60% AA diets for 10 days compared with rats fed 20% and 60% casein diets; and (3) measured the abundance of mRNA for four trypsinogen isozymes after chronic administration of CCK. Trypsin activities were gradually increased in both the pancreas and the small intestinal lumen and reached maximum at 5 days after the switch to the 60% AA diet (Exp. 1). This result is evidence that the increase in the protease activity in the pancreas is due to enhancement of pancreatic trypsin production. In experiment 2, pancreatic trypsinogen isozymes I, II, III, and IV mRNA abundance were evaluated by the Northern blotting method using cDNA probes specific for each isozyme mRNA. Abundance of trypsinogen mRNA without trypsinogen I tended to increase in the rats fed the 60% casein diet but tended to decrease in the rats fed the 60% AA diet compared with the respective normal nitrogen level diet groups without significant difference. CCK mRNA abundance in the jejunal mucosa increased as a result of feeding the 60% casein diet, but not the 60% AA diet. Subcutaneous CCK injections (3.5 nmole/kg body weight/day, twice daily, at 8:30 am and 7:30 pm) for 10 days resulted in increased pancreatic trypsin activity, whereas the changes in mRNA of the four trypsinogen isozymes was similar between the 20% and 60% casein groups but differed between the 20% and 60% AA groups (Exp. 3). These results suggest that CCK is not involved in the induction of pancreatic trypsin that occurs with feeding of a high AA diet and that the mechanism of protease induction by dietary AA is different from that in the case of dietary protein.

Journal Article↗

PubMed1998

Possible mechanism of ECG features in patients with idiopathic ventricular fibrillation studied by heart model and computer simulation.

The possible contribution of localized conduction delay and abnormal action potentials to ventricular fibrillation (VF) was studied by applying an anisotropic cardiac computer model to clinical cases of the Brugada-type electrocardiogram (ECG), which shows right bundle branch block (RBBB), a normal QT interval, ST-segment elevation, and late r' in leads V1 and V2. The anisotropic heart model was composed of 50,000 discrete units with a spatial resolution of 1.5 mm and was mounted in a human torso model. The longitudinal/transverse conduction velocity ratio was 3:1. For the normal ECG, a conduction velocity of 0.75 m/s was required. In the abnormal area of the right anterior epicardial wall, the conduction velocity was set at 0.2 m/s, with decreasing action potential amplitude and 10% prolonged action potential duration. The ECG features of ST-segment elevation and Brugada-type right bundle branch block pattern were simulated. The action potential duration was able to change dynamically with coupling interval of stimulation, with a ratio of 9% for normal ventricular muscle and 50% for Purkinje fibers. Five successive stimuli were applied to the left lateral epicardium 300 ms after the first sinus excitation, and sustained VF was induced with the transmural conduction delay at the right anterior ventricle as a block increasing the vulnerability. At the initiation of VF, reentry circuits were shown around the border zone of the right epicardium and were very heterogeneous around the conduction delayed area and septal area. In an area with the characteristics of nontransmural conduction delay, sustained VF was prevented, and the pattern of transient right bundle branch block appeared on the simulated ECG and body surface potential maps. The late r' wave was calculated in the precordial leads and right anterior site on the body surface potential maps. These results suggest that increased multipolarity in the border zone between the Purkinje fibers and delayed conduction area in the right ventricle might play an important role as a functional block for the persistence of VF.

Action Potentials↗

PubMed1997

[Functional foods and drugs: from the clinical pint of view].

The Ministry of Health and Welfare, Japan, has recently approved the functional foods for specific health uses. However, most of Japanese clinicians do not know what the "functional foods" are. From the clinical point of view, I will discuss the possible problems with the functional foods and compare their roles with those of foods and drugs.

Food, Organic↗

PubMed1996

[Clinical use of beta-blocker an as antiarrhythmic agent].

It has been reported that beta-blocker treatment reduces the incidence of sudden cardiac death after myocardial infarction, possibly due to antiischemic and antiarrhythmic effects. Beta adrenoceptor blocking drugs are administered, as an antiarrhythmic agent in patients with hyperthyroidism, atrial fibrillation, atrial flutter and ventricular tachyarrhythmias. Even low dose beta-blocker administration reduces the incidence of PVC's. Beta blockers are expected to decrease the ventricular rate of persistent tachyarrhythmias resulting from excessive cardiac sympathetic tone. Existence of denervated areas in myocardium in the cases of ventricular tachyarrhythmias may be shown in the cardiac scintigram as abnormal myocardial uptake of 123I-MIBG.

Adrenergic beta-Antagonists↗

PubMed1994

Dose escalation of biweekly cyclophosphamide, doxorubicin, vincristine, and prednisolone using recombinant human granulocyte colony stimulating factor in non-Hodgkin's lymphoma.

BACKGROUND: Several uncontrolled trials have suggested that dose intensity of chemotherapy is a crucial determinant of treatment outcome for patients with non-Hodgkin's lymphoma (NHL). To explore the possibility of increasing dose intensity, a dose-escalation study of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) using recombinant human granulocyte colony stimulating factor (rhG-CSF) was initiated. METHODS: First, the feasibility of standard dose CHOP (750 mg/m2 cyclophosphamide intravenously [i.v.] on Day 1;50 mg/m2 doxorubicin i.v. on Day 1; 1.4 mg/m2 vincristine i.v. on Day 1; and 100 mg/body prednisolone orally on Days 1-5) repeated biweekly at the original dose was assessed. rhG-CSF was given subcutaneously at doses of 2-5 micrograms/kg every day or every other day on Days 3-13. The safety of increasing the dose of cyclophosphamide during biweekly CHOP then was tested. Besides the standard dose (750 mg/m2), two dose levels of cyclophosphamide were set (1200 mg/m2 and 1500 mg/m2 in patients younger than 61 years of age, and 1200 mg/m2 in patients 61-75 years old). RESULTS: Twenty-seven patients with NHL who had received minimal or no previous treatment were enrolled in this study. In the 750 mg/m2 group, 9 patients received 3-6 cycles of treatment (mean, 3.9 cycles), in the 1200 mg/m2 group, 10 patients received 3-6 cycles (mean, 4.8), and in the 1500 mg/m2 group, all 8 patients received 6 cycles. No significant differences among the groups were observed in the extent and the duration of neutropenia in each cycle, and a leukocyte count of more than 3000/microliters on Day 15 was achieved in all 131 cycles. Hemoglobin values and platelet counts, however, decreased in the later cycles in the 1500 mg/m2 group. Two patients were hepatitis-B virus carriers, one of whom died of fulminant hepatitis after completion of six cycles. Another patient developed a transient increase of transaminases after the second cycle. One other patient developed Grade 4 mucositis (World Health Organization scale). The numbers of patients who achieved complete and partial responses, respectively, were 4 (50%) and 2 (25%) in the 750 mg/m2 group, 8 (80%) and 2 (20%) in the 1200 mg/m2 group, and 8 (100%) and 0 (0%) in the 1500 mg/m2 group. CONCLUSIONS: The dose of cyclophosphamide in biweekly CHOP can be increased up to 1500 mg/m2 with no increase in the incidence of treatment-related early mortalities without any organ damage in younger patients. The efficacy of this dose intensification of CHOP currently is being investigated in a multicenter prospective randomized trial using three different dose levels of cyclophosphamide.

Adult↗

PubMed1994

Endothelium-dependent relaxation by angiotensin-converting enzyme inhibitors in canine femoral arteries.

The effects of angiotensin-converting enzyme (ACE) inhibitors on vascular reactivity were investigated using isolated canine femoral arteries with and without endothelium. N-N-(S)-1-carboxy-3-phenylpropyl-L-alanyl-N-(indan-2-yl)glycine (M-1; an active metabolite of delapril, a nonsulfhydryl ACE inhibitor) and captopril (a sulfhydryl ACE inhibitor, 10(-8) to 10(-5) M) relaxed in a dose-dependent manner canine femoral arterial rings precontracted with prostaglandin F2 alpha in the presence of endothelium only. The endothelium-dependent relaxations by M-1 and captopril were completely blocked by methylene blue, an inhibitor of soluble guanylate cyclase; NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis; and oxyhemoglobin, an inactivator of nitric oxide; they were partially blocked by aspirin, an inhibitor of cyclooxygenase and were enhanced by superoxide dismutase, a radical scavenger. The inhibitory effect of L-NMMA on the relaxations by M-1 and captopril were reversed by a high dose of L-arginine. Moreover, a bradykinin antagonist partially inhibited these relaxations. These results suggest that endothelium-dependent relaxations by M-1 and captopril in canine femoral arteries are mediated through the release of both prostanoids and endothelium-derived nitric oxide via endogenous bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1994

[A case report of left ventricular-right atrial communication with tricuspid regurgitation due to infective endocarditis].

A case of 58-year-old man with a left ventricular-right atrial communication with tricuspid regurgitation due to infective endocarditis was reported. Surgical treatment was performed following intensive chemotherapy. The communication was found in the center of a vegetation on the septal leaflet. Closure of the communication and replacement of the tricuspid valve were done successfully. His postoperative course was uneventful.

Endocarditis, Bacterial↗

PubMed1993

Phase IV group study of natural human interferon alpha (HLBI) on chronic myelogeneous leukaemia.

Under the control of Kanagawa CML/HLBI phase IV study group in Japan, 18 cases out of registered 30 cases of chronic myelogeneous leukaemia consisting of 17 chronic phase and 1 accelerated phase, during July, 1991 to January, 1992, were analyzed for their hematological responses and cytogentic responses preliminarily. Hematological response rate (PR + CR) was 83.3% including 50.0% of CR, as judged by Kimura's criteria after treatment with HLBI alone (16 cases) or/and with other chemotherapy (2 cases). The dosage and duration of HLBI therapy required to get into the complete remission ranged from 212 to 1272 millions IU and between 6 to 42 weeks (mean value was 20 weeks), respectively. The clonally proliferated leukocytes and decreased physiological hematopoiesis started to recover from 2 to 4 weeks and reached their normal ranges from 16 weeks after 6 millions IU of HLBI were administered every day. In the 4 cases examined, 3 cases showed minimal cytogenetic responses and a case showed no cytogenetic response. Slight and temporary adverse effects were observed in 15 out of 18 cases (83.3%) including fever, general malaise, appetite loss, eruption, diarrhea, glossitis, hypogustation, weight loss and local muscle pain.

Adult↗

PubMed1993

[Vasodilator therapy in cardiac failure].

In recent years, vasodilator drugs are considered a standard therapy for patients with symptomatic heart failure. Isosorbide dinitrate, venodilator, shows a striking fall in cardiac filling pressure. Hydralazine, arterially active vasodilator, decreases afterload and increases cardiac output. The combined use of nitrates and hydralazine shows synergistic effect in increasing cardiac output, lowering cardiac filling pressure and improving exercise tolerance and life expectancy. Prazosin showed no favourable effect on survival in a V-HeFT trial. Although calcium antagonists have been expected to improve hemodynamics in the patients with heart failure, there have been no controlled large trial to prove that the hemodynamic effect is accompanied by any improvement in exercise tolerance or quality of life. At the present, it is considered to be reasonable to use nitrates and hydralazine combined with ACE inhibitors, in patients with chronic heart failure.

Adrenergic beta-Antagonists↗

PubMed1991

Acetylcholine-induced endothelium-dependent vascular smooth muscle relaxation in nitroglycerin-tolerant isolated rat aorta.

Nitroglycerin (NTG) tolerance is recognized clinically, and its pharmacological mechanism has been thought to be due to a decrease in the accumulation of cyclic GMP (cGMP) which is a second messenger of NTG. Endothelium-derived relaxing factor (EDRF) also relaxes vascular smooth muscle through the activation of soluble guanylate cyclase and the production of cGMP. The purpose of this study was to investigate acetylcholine (ACh)-induced endothelium-dependent relaxation and cGMP response in NTG-tolerant isolated rat aorta. Ring strips prepared from the thoracic aorta of male Wistar rats were mounted in tissue baths and contracted with 10(-6) M norepinephrine. NTG and ACh relaxation responses were compared before and after 1 h treatment with 5 x 10(-4) M NTG. The chronological changes in tissue cGMP levels by 10(-6) M NTG and ACh were compared between a control group (untreated) and NTG-tolerant group (treated with 5 x 10(-4) M NTG for 1 h). The NTG dose-response curve shifted markedly to the right, but the ACh dose-response curve shifted to the left after the induction of NTG tolerance. In the control group, both NTG and ACh elevated the tissue cGMP levels, but in the NTG-tolerant group only ACh elevated cGMP significantly. However, in the NTG-tolerant group, the cGMP increase induced by ACh was smaller than that in the control group. These results suggest that NTG tolerance does not decrease, but rather augments ACh-induced endothelium-dependent vascular smooth muscle relaxation in isolated rat aorta.

Acetylcholine↗

PubMed1990

Stretch may enhance the release of endothelium-derived relaxing factor in rabbit aorta.

The effect of vascular stretch on the release of EDRF was studied by measuring tissue cGMP levels of rabbit. Aortic rings of rabbit were quick-frozen in liquid nitrogen during varying resting tensions, and cGMP contents were determined by radio-immunoassay. The tissue cGMP levels significantly elevated with the increase in resting tension in endothelium-intact rings, but not in endothelium-denuded rings. Deprivation of extracellular calcium abolished the stretch-induced elevation of tissue cGMP levels in endothelium-intact segments. These stretch-induced endothelium dependent tissue cGMP elevations were unaffected by Ca2+ channel blockers, nicardipine and diltiazem. Data suggest that vascular stretch may release EDRF via mechanism dependent on extracellular calcium, but probably not through voltage-dependent calcium channel.

Animals↗

PubMed1990

Vascular smooth muscle relaxation induced by epidermal growth factor is endothelium-dependent.

Epidermal growth factor (EGF) is released from platelets during aggregation. Because we thought that EGF played a role in vascular tone, we investigated its vascular reactivity using isolated rat aortic strips with and without the endothelium. In the presence of endothelium, EGF relaxed vascular smooth muscle precontracted with 40 mM K+, 10(-5) M prostaglandin F2 alpha or 10(-6) M norepinephrine. The relaxation induced by EGF was more prominent on the prostaglandin F2 alpha- and norepinephrine-induced contractions than on the K(+)-induced contraction. Atropine (10(-5) M) and aspirin (10(-5) M) had no effect on the EGF-induced relaxation, but methylene blue (10(-5) M) partly abolished the relaxation evoked by EGF. These results suggest that EGF relaxes vascular smooth muscle in the presence of the endothelium. They also suggest that EGF has an effect on the endothelium to produce relaxing factor independent of cyclooxygenase; the releasing factor activates soluble guanylate cyclase, resulting in relaxation of vascular smooth muscle through the production of cyclic GMP.

Animals↗

PubMed1990

Vascular smooth muscle relaxation by endothelium-dependent beta 1-adrenergic action.

1. Norepinephrine (NE) (10(-5) M) in rabbit aorta relaxed ring segments with endothelium precontracted with 10(-6) M NE, but not segments without endothelium. 2. The relaxation was inhibited with metoprolol and methylene blue, but not inhibited with yohimbine and indomethacin. 3. NE (10(-5) M) significantly elevated tissue c-GMP levels in segments with endothelium. 4. These studies suggest that the vascular relaxation by high doses of NE is mediated by the release of endothelium-derived relaxing factor (EDRF) induced by the stimulation of beta 1-adrenoceptor.

Animals↗

PubMed1990

[An autopsied case of juvenile myocarditis which showed a remarkable cardiac enlargement during the course of six months].

A 19-year-old student was admitted for orthopnea. He had been a badminton player having no experience of serious diseases until he became aware of exertional epigastralgia ten days before admission. On examination, blood pressure was 102/70 mmHg, heart rate 148, and respiration 34. A third sound and moist rales were heard. The liver was enlarged and palpable at 8 cm below the right costal margin. The titers of the virus neutralizing antibodies determined on admission were all less than 32-fold. Chest roentgenogram as compared with that taken six months before admission showed a marked increase in the cardiothoracic ratio and pulmonary venous congestion. Echocardiogram showed a markedly dilated cavity of the left ventricule (LV) (LV diastolic diameter = 74 mm) compared with the cavity of the right ventricule (RV) (RV diastolic diameter = 20 mm) and diffusely impaired wall motion of the LV (fractional shortening = 9%). He died of intractable congestive heart failure two weeks after admission. Heart weight was 620 g. The LV cavity was markedly dilated, but the thickness of the LV free wall was within normal limits. Microscopy of the both atria, the RV, and the basal ventricular septum showed acute and chronic-staged inflammation. However, microscopy of the free wall of the LV showed only slight interstitial fibrosis without necrosis of the myocytes. The marked dilatation of the LV cavity would be due to either the same mechanism as that of dilated cardiomyopathy or excessive exercise after infection with myocarditis. This case showed that LV dilatation without myocardial necrosis/degeneration could develop among patients with myocarditis.

Adult↗

PubMed1989

Inhibition of development of tolerance to nitroglycerin by preventive administration of N-acetylcysteine in rats.

The efficacy of N-acetylcysteine in reversing nitrate tolerance has been controversial. This study examined whether continuous administration of N-acetylcysteine, a sulfhydryl compound, can prevent the development of tolerance to nitroglycerin; its acute effects on developed tolerance were also assessed. Rats were treated with subcutaneous injections of 1) 100 mg/kg nitroglycerin, 2) 100 mg/kg nitroglycerin and 700 mg/kg N-acetylcysteine, 3 times a day for 3 days. The sensitivity to nitroglycerin was studied in aortic preparations. The degree of developed tolerance to nitroglycerin was partially inhibited by simultaneous injection of N-acetylcysteine. Subsequent in vitro preincubation of aortic strips with nitroglycerin (10(-5) M) reduced the subsequent nitroglycerin sensitivity of vessels from rats treated with nitroglycerin and N-acetylcysteine; sensitivity returned to the initial control level after in vitro preincubation with N-acetylcysteine. The nitroglycerin sensitivity of vessels from rats treated only with nitroglycerin, though, was not affected by in vitro preincubation with N-acetylcysteine. In conclusion, N-acetylcysteine is not effective in reversing the high degree of tolerance developed to nitroglycerin. However, continuous administration of N-acetylcysteine is effective in preventing the development of nitroglycerin tolerance.

Acetylcysteine↗

PubMed1989

[Prediction of coronary artery disease using post exercise T wave change].

In the evaluation of the exercise stress test, conventional electrocardiographic criteria using 1 or 2 mm ST segment depression below the isoelectric line yields many false positive results and is not so useful to predict the severity of coronary artery disease. In this study, we have attempted to predict the presence and the severity of coronary artery disease from the post exercise T wave change. Fifty-six patients who had positive treadmill exercise test results by conventional ST segment criteria and underwent selective coronary arteriography were studied. T wave change was defined as inversion or biphasic change in one or more of leads aVF, V4, V5, V6 during the recovery phase, and in the cases who showed T wave changes, T wave configuration were also analysed. Seventeen of 28 patients with and 11 of 28 patients without significant coronary artery disease showed post exercise T wave changes. This difference was not statistically significant. But in the cases who showed T wave changes, the maximum amplitude of the negative component of T wave was significantly greater in the true positive group than in the false positive group. And the development of deeply negative component (more than 1.5 mm) indicated the presence of multivessel coronary artery disease. In the cases who showed the negative component of T wave less than 1 mm, the characteristics of T wave configuration including the amplitude, height of positive component, and the depth from the isoelectric line were different between the 2 groups. These results suggest that careful observation of T wave during the recovery phase is useful to improve the diagnostic accuracy of the exercise electrocardiogram.

Adult↗

PubMed1988

Comparison of functional responses of canine coronary artery and saphenous vein.

Functional responses of canine circumflex coronary arteries and saphenous veins before and after grafting surgery were assessed following physiologic and pharmacologic interventions. Developed tension of ringed segments of vessels was recorded isometrically. Dose-dependent responses to norepinephrine revealed significantly greater responses of saphenous veins than coronary arteries (maximal responses were 2.79 +/- 0.45 and 0.44 +/- 0.34 g, respectively; p less than 0.001). Sensitivity to norepinephrine [as evaluated by 50% effective dose (ED50) value] was 3.3 times greater in the saphenous veins (p less than 0.001). STA2, a synthetic thromboxane A2 analog (see Methods), produced similar contractions of both vessels [maximal responses were 2.13 +/- 0.37 g in saphenous vein and 1.64 +/- 0.85 g in coronary artery; p less than not significant (NS)], while sensitivity to STA2 of saphenous veins was 3.1 times greater than that of coronary arteries (p less than 0.001). In contrast to the foregoing responses, coronary arteries demonstrated significantly greater responses to potassium than saphenous veins (maximal responses were 2.16 +/- 0.71 g and 1.40 +/- 0.56 g, respectively; p less than 0.001). Moreover, coronary arteries revealed 1.6 times greater sensitivity than saphenous veins (p less than 0.001). When saphenous veins were transplanted into the femoral artery, the segments of the grafts (2 weeks or 3 months after surgery) revealed 4.0 and 1.7 times greater sensitivity (denervation supersensitivity) to norepinephrine and potassium than those of the control veins (p less than 0.01, respectively). Contractile tension response, however, decreased by at least 50% 3 months after surgery, most probably due to a thickened vessel wall and a reduced compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗