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Biomedical subjects

N Harada

Publications and source records attributed to N Harada.

At least 613 records · Page 34Linked to original sources
PubMed1984

Purification and characterization of four forms of cytochrome P-450 from liver microsomes of phenobarbital-treated and 3-methylcholanthrene-treated rats.

Four forms of cytochrome P-450, tentatively designated PB-1, PB-2, MC-1, and MC-2, were purified from liver microsomes of rats treated with phenobarbital (PB-1 and PB-2) or 3-methylcholanthrene (MC-1 and MC-2). Each purified form showed a single protein-staining band on SDS-polyacrylamide gel electrophoresis giving a minimum molecular weight of 56,000 (MC-1), 53,000 (PB-1), 53,000 (MC-2), or 49,000 (PB-2). PB-1 and MC-1 were the major cytochrome P-450 components inducible by phenobarbital (PB) and 3-methylcholanthrene (MC), respectively. Antibodies prepared against each form of purified cytochrome P-450 did not cross-react with heterologous antigens in Ouchterlony double diffusion tests, confirming the immunological distinctness of the four forms. The CO-compounds of reduced PB-1 and PB-2 had an absorption maximum at 450 nm, whereas those of MC-1 and MC-2 had a maximum at 447 nm. Judging from the oxidized absolute spectra, MC-2 was of high spin type and the others were of low spin type. Amino acid analysis revealed considerable differences among the purified four forms of cytochrome P-450, and the amino acid sequences of their NH2-terminal portions confirmed that the four forms were different proteins. In a reconstituted system containing NADPH and NADPH-cytochrome P-450 reductase, PB-1 and PB-2 oxidized benzphetamine at high rates, but their oxidation of benzo(a)pyrene was much slower than that by MC-1, which catalyzed rapid hydroxylation of benzo(a)pyrene but had low activity with benzphetamine. The quantity of each form of cytochrome P-450 in microsomes was determined by quantitative immunoprecipitation, and selective induction of PB-1 and MC-1 by PB and MC, respectively, was confirmed. Some induction of PB-2 and MC-2 by the corresponding inducers was also noticed. PB group P-450's were not increased by MC treatment, nor were MC group P-450's by PB.

Amino Acids↗
PubMed1984

[Abnormal ECG and adrenaline-induced arrhythmias in restraint and water immersion stressed mice and effects of oxprenolol].

Male ddY mice were loaded with restraint and water immersion stress (RWIS) for 1 hr, and their ECG was measured by lead II. A considerable decrease of heart rate and remarkable prolongations of PQ, QT and QRS intervals were observed in the ECG of RWIS mice. Then experimental arrhythmias were induced by methacholine or adrenaline (Adr) on RWIS mice, and their frequencies of appearance were examined. The appearances of methacholine-induced ventricular extrasystole, atrio-ventricular (A-V) block, sino-atrial (S-A) block and sinus standstill were higher in RWIS mice than in normal mice, and the appearances of sinus arrhythmia and supraventricular extrasystole were similar to normal mice. The appearance of Adr-induced arrhythmia of any type was significantly higher in RWIS mice than in normal mice. Then protective effects of 3 beta-blockers, oxprenolol, propranolol and carteolol, on the worsening of Adr-induced arrhythmias on RWIS mice were studied. A single administration of 5 or 10 mg/kg of oxprenolol or 5 mg/kg of propranolol inhibited the appearance of extrasystole and A-V block. The effectiveness of three-times administrations of 1 approximately 10 mg/kg of oxprenolol was similar to that of the single administration. These results suggest that oxprenolol shows a strong antiarrhythmic effect by continuous administrations on chronic syndromes in SART mice, and it shows an immediate effect by a single administration on acute syndromes in RWIS mice.

Acute Disease↗
PubMed1984

[The abnormal ECG and the appearance of methacholine-induced arrhythmias in SART mice and effects of beta-blockers, oxprenolol, propranolol, and carteolol].

Protective effects of beta-blockers (oxprenolol, propranolol and carteolol) on the abnormal ECG of the sympathicotonia type were studied in male ddY SART stressed mice. Oxprenolol and carteolol were observed to have mild effects on the abnormal ECG as compared with propranolol. Experimental arrhythmias were induced by drugs in SART mice, and their frequencies of appearance were examined. The types of arrhythmias used as indices were sinus arrhythmia, supraventricular and ventricular extrasystole, the 1st and 2nd degrees of atrio-ventricular (A-V) block, sino-atrial (S-A) block and sinus standstill. The frequency of appearance of arrhythmia of any type induced by adrenaline was lower in SART mice than in normal mice. The frequency of appearance of methacholine (MCh)-induced arrhythmia of any type was significantly higher in SART mice than in normal mice. Protective effects of the 3 beta-blockers on the worsening of MCh-arrhythmias in SART mice were studied. With a single dose of 5 or 10 mg/kg, the drugs were effective on supraventricular extrasystole and S-A block. Continuous administrations of oxprenolol and carteolol inhibited the occurrence of supraventricular extrasystole, A-V block and S-A block, but not the occurrence of ventricular extrasystole. Continuous administrations of propranolol were effective on any type of arrhythmias except for sinus arrhythmia. These results further support our viewpoint that the SART mouse is of the sympathicotonia type with respect to the heart, and they suggest that oxprenolol and carteolol may be effective clinically on arrhythmias caused by autonomic imbalance.

Animals↗
PubMed1984

[Studies on the mechanism of antitumor activity of 5-FU and its derivatives--relationship between the inhibition of tumor growth and the inhibition of thymidylate synthetase in vivo].

The relationship between the antitumor activity and the inhibition of thymidylate synthase after oral administration of 5-FU, FT-207 or UFT was examined. The inhibition of tumor growth on sarcoma-180 after oral administration of 5-FU (20 mg/kg), FT-207 (120 mg/kg) or UFT (30 mg/kg) was 40%, 50% or 70%, respectively. It was found that the inhibition of thymidylate synthase in sarcoma-180 tumor tissue after single oral administration of 5-FU (20 mg/kg), FT-207 (30 or 120 mg/kg) or UFT (30 mg/kg) were about 45%, 20%, 50% or 65%, respectively, but the activities of other enzymes involved in DNA synthesis were not almost inhibited. Thymidylate synthase was inhibited more severely by oral administration of UFT (30 mg/kg). The activities of other enzymes were not inhibited even by continuous oral administration of these drugs for 6 or 11 days. The extent of inhibition of thymidylate synthase seemed to be parallel to that of inhibition of tumor growth. These results suggest that the inhibition of thymidylate synthase by FdUMP converted from 5-FU, FT-207 or UFT plays a major role in their antitumor actions.

Animals↗
PubMed1984

[Morphological studies on the pathogenesis and treatment of hepatolithiasis].

Review of 108 patients with hepatolithiasis showed a recent increase of primary intrahepatic gallstones. 55 per cent of cases with hepatolithiasis had their gallstones in the left intrahepatic bile ducts. Clinicopathological study on the resected hepatic specimens of 33 patients revealed numerous intrahepatic periductal glandular formations. Periductal glandular formations were classified into the intramural and extramural glands. The mucous substances which might had been released from the periductal glands seemed to play a role in the formation of stones in combination with bilirubin pigments, cholesterin, bacterial organisms, cellular debris and other bile component. Intrahepatic gallstones and extramural glands were seen in the intrahepatic segment and area ducts. The defunctionalized atrophic hepatic lobe or segment should be resected in order to remove the calculi completely and to prevent the recurrence.

Adolescent↗
PubMed1984

Characterization of the activity of growth factor from AH-130 tumor cells.

The activation of DNA synthesis induced by growth factor from the cytosol of AH-130 tumor cells (AH-130GF) was inhibited by alkylamines (methylamine, ethylamine, and dansylcadaverine), which inhibit the intracellular processing of hormone-receptor complexes. Calmodulin inhibitors (trifluoperazine and W-7) also inhibited the mitogenic action of AH-130GF, suggesting that the Ca-calmodulin system and proteolytic processing in lysosomes are necessary for stimulation of DNA synthesis by AH-130GF after its binding to the cell surface. Membrane phosphorylation induced by AH-130GF or epidermal growth factor (EGF) was investigated by using rat liver plasma membranes and 3T3 cell membranes in vitro. EGF increased the phosphorylation of two protein components with molecular weights of 160K and 130K in rat plasma membranes, but AH-130GF increased the phosphorylation of only the 130K protein. No specific phosphorylation induced by AH-130GF was detected in 3T3 cell membranes, but EGF induced phosphorylation of the 160K receptor protein.

Animals↗
PubMed1983

Effect of an exogenous energy source and amino acids on DNA synthesis in regenerating rat liver.

Rats on a protein-free diet synthesized less DNA after partial hepatectomy than rats on a normal diet. In regenerating livers of animals on the protein-free diet, induction of several enzymes involved in the DNA precursor synthetic pathway, and especially ribonucleotide reductase, were depressed. When young rats were maintained solely by parenteral nutrition after partial hepatectomy, exogenous amino acids were more important than the exogenous energy source for induction of enzymes involved in synthesis of DNA and its pyrimidine nucleotide precursors. In particular, induction of ribonucleotide reductase appeared to be controlled by exogenous amino acids. Tryptophan, methionine, phenylalanine, leucine, valine, isoleucine and threonine seemed to stimulate the induction of this enzyme most after partial hepatectomy.

Amino Acids↗
PubMed1983

Phenobarbital- and 3-methylcholanthrene-induced synthesis of two different molecular species of microsomal cytochrome P-450 in rat liver.

The syntheses of two different molecular species of cytochrome P-450, P-450(PB), and P-450(MC), were examined using normal and drug-treated rats, and the rate of synthesis was correlated with the drug-induced increase of the amounts in the liver microsomes of treated animals. Phenobarbital (PB) and 3-methylcholanthrene (MC) were used as inducers. The syntheses of cytochrome b5 and NADPH-cytochrome P-450 reductase (fpT) were also examined. In vivo incorporation of L-[3H]leucine indicated a large increase of P-450(PB) synthesis in the livers of PB-treated animals, which reached a plateau value about 18-fold higher than the control level at 12 h. The synthesis of fpT was also stimulated by PB showing a peak value of 3 times the control at 12 h after PB administration, but it returned to the control level afterwards. On the other hand, the syntheses of P-450(MC) and cytochrome b5 did not change at all. Similarly, MC administration selectively induced the synthesis of P-450(MC), which was about 24 times the control at 6 h, whereas those of P-450(PB), cytochrome b5, and fpT were not affected by MC. Analysis of nascent peptides and in vitro translation of polysomes and total liver RNA prepared from control and drug-treated animals were also carried out, and the results of these in vitro experiments confirmed the observations in in vivo incorporation studies. It was found that both free and membrane-bound ribosomes participate in the syntheses of P-450(PB) and P-450(MC) in the case of control animals. PB and MC induced the syntheses of P-450(PB) and P-450(MC) by bound ribosomes but not by free ribosomes, and the contribution of bound ribosomes to the syntheses of these two species of cytochrome P-450 was predominant in the case of drug-treated animals. The molecular sizes of in vitro synthesized P-450(PB) and P-450(MC) were the same as those of authentic samples prepared from liver microsomes.

Animals↗
PubMed1983

Kinetics of rouleaux formation using TV image analyzer. I. Human erythrocytes.

An apparatus for determining the velocity of erythrocyte rouleaux formation was constructed, combining an inverted microscope, a transparent cone-plate viscometer, a TV image analyzer, and a computer. At lower shear rates, the overall process is the sedimentation and the rouleaux formation followed by the development of three-dimensional aggregates. The individual erythrocyte could be observed and the process was expressed by the time courses of the changes in the count and area of particles; taking the computed increment in the area/count, the rate of rouleaux formation could be estimated. The effects of shear rates, hematocrits, plasma proteins, and pH were quantified. The rate of rouleaux formation in autologous plasma increased by (1) lowering the shear rates (1.9 less than or equal to gamma less than or equal to 15 s-1),2) increasing the hematocrit (up to 0.6%), 3) adding human fibrinogen (up to 600 mg/dl) or gamma-globulin, and 4) increasing pH. The transformation to echinocytes or to stomatocytes decreased the rate of rouleaux formation. The pH effect was explained by the increase in mean corpuscular volume at lower pH rather than by the changes in the electrostatic repulsion or in the protein binding.

Blood Proteins↗
PubMed1983

[Seasonal variation of circulatory and sensory functions during immersion test in cold water].

For early diagnosis of vibration syndrome, peripheral circulation and sensory tests after cold water immersion of the upper extremities are being performed widely in Japan. The authors studied the seasonal effect on the immersion test and its influence on diagnosis of vibration syndrome. Eight healthy male subjects, aged from 28 to 39, were examined. The immersion tests were conducted in winter (February), spring (May), summer (August) and autumn (November) in Ube city, Japan (Table 1). The room temperatures were maintained at 10 degrees C, 20 degrees C and 30 degrees C during the tests at each season. As to the exposure-to-cold test, the left hand of subject was immersed in stirred water at 10 degrees C for ten minutes, and the changes of peripheral circulatory function and sensory function were measured. Peripheral circulatory function was assessed by the skin temperature of middle finger and the value of the nail press test on the index finger. Sensory function was assessed by 125 Hz vibratory sense threshold and pain threshold of the middle finger. The finger skin temperature was lower in autumn and winter, followed by spring, and highest in summer. In particular, the finger skin temperature in autumn was lower than that in winter at the condition of room temperature at 30 degrees C, which is considered to be less effected by heat content in the body (Fig. 1, Table 3). The frequency of the appearance of cold induced vasodilation was also lower in autumn than that in winter (Table 2). These findings suggest that the tonus of the vasoconstrictor in the skin vessels of finger is strongest in autumn, followed by winter. It is also suggested that the tonus remains slightly strong in spring and is weakest in summer. Furthermore, the seasonal variations in the value of the nail press test, vibratory sense threshold and pain threshold were observed at some points of measuring time during immersion test (Figs. 2-4). Of these, the variations in the value of the nail press test and vibratory sense threshold were considered to be secondary to the seasonal variation of peripheral circulatory function (Fig.6). The variation in pain threshold was considered to result from paresthesia developing in the lower room temperature at 10 degrees C. The pain of finger during immersion test was also effected by season but the range of variation was not significant (Fig.5).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1983

[Evaluation of the lipid and glucose metabolism on the apancreatic status with insulin supplement and with pancreatic autotransplantation].

To evaluate the effect of pancreatic fragments transplantation on glucose and lipid metabolism in the apancreatic status, 22 healthy mongrel dogs were totally pancreatectomized and then divided into three groups, (1) 5 dogs without any supplement , (2) 5 dogs with insulin replacement, and (3) 12 dogs with additional pancreatic fragments transplantation. In these three groups, changes in fasting plasma sugar, triglyceride, total cholesterol, phospholipid and lipoprotein fractions were studied. Stability of serum glucose levels were compared between the dogs with insulin replacement and those with transplantation by using glucose infusion and insulin test. Without insulin replacement or transplantation, apancreatic dogs showed high serum glucose levels immediately after total pancreatectomy. With pancreatic transplantation, serum glucose levels and lipids were well controlled within normal limits for a long time period after the operation. However, in the dogs with insulin replacement, serum glucose levels and lipids were remarkably unstable in fasting period and also showed easily tendencies to become hypoglycemic status by insulin test and diabetic ketoacidosis by glucose infusion test as compared with those in the transplanted dogs.

Animals↗
PubMed1983

[Pharmacological studies on the mechanisms of asebotoxin III-induced centrogenic pulmonary hemorrhagic edema in guinea pigs].

Asebotoxin III (ATX-III), a diterpenoid isolated from the leaves of Asebi, Pieris japonica, was found to produce hemorrhage into the lungs when the toxin in a dose of 2-8 micrograms was injected into the lateral ventricle of guinea pigs under urethane anesthesia (0.8 g/kg, i.p.). The occurrence of the lung hemorrhage was associated with a hypertensive response which was two times higher than the control level. The hemorrhage first occurred at a time when systemic blood pressure reached its highest level. This was verified by X-ray examination on the chest of the guinea pig. In contrast to the hemorrhage into the lungs, the other organs in the abdominal cavity were found to be rather ischemic in the autopsy cases. Death due to hemorrhage into the lungs was effectively prevented by pretreating the guinea pigs with phentolamine mesylate (1 mg/kg, i.v.) and 6-hydroxydopamine hydrobromide (40 mg/kg, i.p.). Time before death was significantly prolonged by treating the animals with reserpine (5 mg/kg, i.m.), chlorpromazine hydrochloride (10 mg/kg, i.v.), guanethidine sulfate (20 mg/kg, i.v.), and hexamethonium bromide (5 mg/kg, i.v.), though death from the lung hemorrhage was not completely blocked. The hemorrhage was aggravated by pretreatment with atropine sulfate (5 mg/kg, i.v.). EEG recordings from the hypothalamus of guinea pigs with ATX-III injection showed an exciting pattern of waves of high frequency and spike discharge. On the mechanisms for the lung hemorrhage induced by ATX-III, we concluded that the toxin produced depolarization of some neurones in the hypothalamus, thereby provoking massive sympathetic discharge for producing severe pulmonary hypertension and hemorrhage.

Animals↗
PubMed1982

Antibradykinin active material in Aloe saponaria.

A material having antibradykinin activity on isolated guinea pig ileum was partially purified from the nondialysate of the pulp of Aloe saponaria by repetition of gel chromatography using a hydrophilic polyvinyl gel and dextran gels. From the results of amino acid and carbohydrate analyses, the antibradykinin-active material was estimated to be a glycoprotein. It was found that this material catalyzes the hydrolysis of bradykinin at pH 7.4. The results of peptide analysis using reversed-phase high-performance liquid chromatography coupled with amino acid analysis indicate that this glycoprotein cleaves the Gly4-Phe5 and Pro7-Phe8 bonds of the bradykinin molecule.

Aloe↗
PubMed1982

Reoperative surgery in cholelithiasis.

From 1965 to 1980, reoperations for residual or recurrent stones were performed on 78 out of 962 Japanese patients with cholelithiasis. The majority of patients who required reoperation had intrahepatic stones. Most of the causes of reoperation were residual stones due to incomplete removal or the non-detection of intrahepatic stones at the previous surgery. Very careful examination of the intrahepatic biliary trees should be done in patients with biliary tract diseases, because in many, the first operation was done during their youth. To remove the intrahepatic calculi completely, hepatic lobectomy should be considered as a final procedure. The causes of reoperation of common duct stones were residual in 60 per cent and recurrent in 40 per cent. Definitive surgery should be done at the first or at least the second operation to avoid irreversible hepatic disorders which have untoward effects on the prognosis. It is important not only to remove the stones but also to relieve the bile stasis in the biliary tract.

Aged↗
PubMed1982

Effect of acetylcholine and new cholinergic derivative on amylase output, insulin, glucagon, and somatostatin secretions from perfused isolated rat pancreas.

The effect of infused acetylcholine and (2-acetyllactoyloxyethyl)-trimethylammonium hemi-1,5-naphthalenedisulfonate (aclatonium napadisilate), a new cholinergic drug . On endocrine and exocrine secretory responses was simultaneously investigated during the perfusion of isolated rat pancreases. Acetylcholine (1.1 microM) stimulated the output of pancreatic juice and amylase, and significantly elicited the production of both insulin and glucagon. Its effect on somatostatin secretion, however, was minimal. Both pancreatic juice flow and amylase output were also significantly stimulated by aclatonium napadisilate (12 microM). These stimulatory effects of aclatonium napadisilate on the exocrine pancreas were blocked by atropine (25 microM). Aclatonium napadisilate could stimulate glucagon, but could not influence insulin and somatostatin secretion. The addition of atropine had no effect on the release of insulin, glucagon, and somatostatin. These results indicate that the effects of aclatonium napadisilate is cholinergic, and that the action is muscarinic. In addition, it can be concluded that pancreatic somatostatin secretion, as well as other hormones from islet cells, is controlled by the parasympathetic nervous system.

Acetylcholine↗