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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 793 records · Page 44Linked to original sources

Perfusion technique of suckling rat liver, and comparison of cytologic and biochemical properties between hepatocytes isolated from suckling and adult rats.

Collagenase-liver-perfusion technique, currently used with adult rat liver, was applied to isolation of hepatocytes from suckling rat liver. The total hepatocyte numbers isolated from suckling rats by collagenase-liver-perfusion technique were 9-fold higher than those by non-perfusion technique. The yield and viability of isolated hepatocytes from suckling rats were 18.1 X 10(7) cells per gram liver and 95%, respectively. The cell yield per gram liver and viability from suckling rats were 185% and 112% of those from adult ones, respectively. In comparison with adult rat hepatocytes, suckling rat hepatocytes were smaller and more homogeneous. The percentage (3.1%) of binucleate cells in the hepatocytes isolated from suckling rats was about one tenth of that (30.7%) in the hepatocytes isolated from adult rats. The isolated suckling rat hepatocytes had higher tyrosine aminotransferase (TAT) and glucose-6-phosphate (G6Pase) activities than adult ones. Suckling and adult rat hepatocytes were transferred to primary culture to compare their cell number kinetics and functional longevities. The functional longevities of those hepatocytes were assessed by their capacity to secrete albumin and alpha-fetoprotein (AFP) into the culture medium and to express TAT and G6Pase activities up to day 6 of primary culture.

Albumins↗

Combined therapy of polyamine antimetabolites and antitumor drugs for human gastric cancer xenotransplanted into nude mice.

Antitumor therapies using polyamine antimetabolites combined with 1-(4-amino-2-methyl-5-pyrimidyl)methyl-3(2-chloroethyl)-3-nitrosourea (ACNU) or fluorinated pyrimidines for human gastric cancer xenotransplanted into nude mice were studied to determine inhibiting post-therapeutic regrowth of the tumor after cessation of antitumor treatments with polyamine antimetabolites alone. ACNU 20 mg/kg, fluorinated pyrimidine, 5-FU 52.8 mg/kg and 5'-deoxy-5-fluorouridine (5'-DFUR) 100 mg/kg as well as polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) 1000 mg/kg and methylglyoxal-bis-guanylhydrazone (MGBG) 50 mg/kg were given intraperitoneally for 5 successive days. When DFMO and MGBG were combined with ACNU, the post-therapeutic regrowth was definitely inhibited, while combined treatments with 5-FU or 5'-DFUR did not inhibit the regrowth. Post-therapeutic DNA biosynthesis was suppressed in mice given DFMO, MGBG plus ACNU. On the contrary, in mice treated with DFMO, MGBG plus 5-FU or 5'-DFUR, suppression of DNA biosynthesis was not observed. Tumor tissue spermine levels in the DFMO, MGBG plus 5-FU or 5'-DFUR group remained unchanged, compared to those in the DFMO + MGBG group. In mice given DFMO, MGBG plus ACNU, however, spermine levels were markedly depressed; and the ACNU alone depressed also the tissue spermine levels. These different results between nitrosourea and fluorinated pyrimidines may relate to mechanisms of action of these antitumor drugs.

Animals↗

Hypertensive putaminal hemorrhage: analysis of 182 patients.

The results of treatment for 182 patients with hypertensive putaminal hemorrhage are described. The patients are graded according to the level of consciousness on admission; grade 1, fully conscious; grade 2, somnolent; grade 3, stuporous; grade 4, semicomatose; and grade 5, deeply comatose. Removal of hemorrhage was performed in 44 patients (24%), and conservative treatment was given in 138 patients (76%). One-month mortality in the surgical group was 27%; it was 22% in the conservative group. At 6 months after surgical treatment, the percentages of patients who returned to full-time work or independent life without disability or with minimal disability (good recovery) were 40% in grade 1, 30% in grade 2, 22% in grade 3, 11% in grade 4, and 0% in grade 5; after conservative treatment, percentages with good recovery were 77% in grade 1, 56% in grade 2, 29% in grade 3, 7% in grade 4, and 0% in grade 5. This study shows that surgical treatment does not give better results in the management of hypertensive putaminal hemorrhage.

Activities of Daily Living↗

Alteration of the turnover of dopamine and 5-hydroxytryptamine in rat brain associated with hypothermia.

The alteration of monoamines and their metabolites in the brain in response to hypothermia was studied using rats subjected to a cold and immobilization stress. The experiments were designed to compare the responses in the "hypothermal" rats with those in the "normothermal" ones which received the same stress except for the change in body temperature. It has been found that the contents of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) in various cerebral regions were significantly decreased during hypothermia. These decreases were readily reversed by the rewarming of animals. Moreover, the increase in the content of 5-hydroxyindole-3-acetic acid (5-HIAA), the metabolite of 5-HT, was also detected in some cerebral regions where the decrease of 5-HT was observed. Although the dopamine (DA) contents in all cerebral regions examined were found to be unaltered, its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and/or homovanillic acid (HVA) contents in most regions in the brain showed a significant elevation during and/or after the occurrence of hypothermia. These results suggest that the metabolic turnovers of 5-HT and DA in various cerebral regions may be accelerated during hypothermia.

3,4-Dihydroxyphenylacetic Acid↗

Hypothalamic control of pituitary and adrenal hormones during hypothermia.

In order to investigate neuroendocrinological mechanisms of hypothermia, we determined the changes in plasma concentrations of corticosterone (CS), prolactin (PRL), and thyrotropin (TSH), and their correlations with alterations in hypothalamic dopamine (DA) and thyrotropin releasing hormone (TRH), in rats restrained and immersed in a water bath at various temperatures. A graded decrease of body temperature induced a progressive increase in the plasma level of CS, whereas that of PRL showed a drastic decrease. The plasma level of TSH also showed an increase during mild hypothermia (about 35 degrees C), but this increase was not evident during profound hypothermia (below 24 degrees C). The changes in these hormones were readily reversed by rewarming animals. Although DA content in the hypothalamus was not affected, its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), showed an increase following the decrease of body temperature. Pretreatment of the animals with sulpiride, a D2-antagonist, prevented the hypothermia-induced inhibition of PRL release. Hypothalamic TRH was significantly decreased during mild hypothermia, and it returned to control levels after rewarming. These results suggest that the decrease in plasma PRL induced by hypothermia may be associated with the activation of hypothalamic DA neurons, whereas the increase in plasma TSH during mild hypothermia seems to be caused by the increased release of TRH in the hypothalamus.

3,4-Dihydroxyphenylacetic Acid↗

Vascular angiotensin converting enzyme in the development of renal hypertension.

The possible role of vascular angiotensin converting enzyme (ACE) is examined in vitro and in vivo. In helically cut strips of arteries isolated from dogs, contractions induced by angiotensin (ANG) I are suppressed by ACE inhibitor or ANG II antagonist. This indicates that vascular ACE contributes to the local formation of ANG II. In two-kidney, one-clip hypertensive rats, plasma-renin activity (PRA) rises rapidly with the elevation of blood pressure, then decreases gradually, despite sustained high blood pressure. Renin activity in the aorta also increases with the development of hypertension and then decreases in parallel with PRA. ACE activity in plasma does not change before or after the unilateral occlusion of the renal artery until after 16 weeks, whereas the enzyme activity in the aorta significantly increases. The conversion rate calculated from the pressor responses, and from the constricting effects of ANG I and ANG II, both in situ and in helically cut strips obtained from chronic hypertensive rats with increased vascular ACE activities, are significantly higher than those obtained from normotensive rats. Vascular ACE, which can effectively produce ANG II from ANG I locally, appears to play an important role in the maintenance of chronic hypertension.

Angiotensin I↗

Vasodilator actions of TRK-100, a new prostaglandin I2 analogue.

TRK-100, a stable analogue of prostaglandin I2 (PGI2), relaxed isolated arteries of the dog precontracted with PGF2 alpha or K+; the relaxation was in the order of mesenteric and renal greater than coronary and femoral greater than basilar and middle cerebral arteries. The relaxation by TRK-100 was not affected by treatment with atropine, propranolol, cimetidine, aminophylline, and indomethacin, but was suppressed by diphloretin phosphate, a prostaglandin antagonist. Treatment with TRK-100 attenuated the contraction induced by PGF2 alpha and Ca2+ in mesenteric and basilar arteries previously exposed to Ca2+-free medium, but did not significantly alter the contractile response to Ca2+ in the arteries exposed to Ca2+-free medium and depolarized by excess K+. TRK-100 and nitroglycerin relaxed isolated mesenteric arteries to a similar extent; however, when continuously infused into mesenteric arteries in anaesthetized dogs, TRK-100 produced greater vasodilatation than nitroglycerin. It is concluded that TRK-100 relaxes dog mesenteric and renal arteries more than cerebral arteries; the relaxation appears to derive from interference with the release of Ca2+ from intracellular stores and with the transmembrane Ca2+ influx through a receptor-operated channel. TRK-100 may vasodilate large and small mesenteric arteries and resistance vessels to a similar extent, whereas nitroglycerin preferentially dilates the large artery.

Animals↗

Cloning in Saccharomyces cerevisiae of a cycloheximide resistance gene from the Candida maltosa genome which modifies ribosomes.

We have previously shown that cycloheximide resistance can be induced in a strain of Candida maltosa by modifying ribosomes (M. Takagi, S. Kawai, Y. Takata, N. Tanaka, M. Sunairi, M. Miyazaki, and K. Yano, J. Gen. Appl. Microbiol. 31:267-275, 1985). The present paper describes the cloning of the gene involved in this resistance (designated RIM-C for ribosome modification by cycloheximide) by using a host-vector system of Saccharomyces cerevisiae.

Candida↗

Quantitative detection of cerebral arteriosclerosis by means of the Doppler ultrasonic technique.

A correlation between the continuity of the cerebral blood flow pattern and the cerebral vascular resistance (namely, cerebral arteriosclerosis) was investigated by the Doppler ultrasonic technique. The following facts were observed. Examination of the brachial blood flow pattern in circulatory stress, i.e., hand-grasping, brachial-binding, cold- and warm-stimulating tests revealed that the more the peripheral vascular resistance was increased, the more was the discontinuity of brachial blood flow pattern increased. Investigation of the continuity of the cerebral blood flow pattern (internal carotid artery) in 18 young healthy persons and 46 elderly patients with cerebral vascular diseases revealed a continuous pattern in all of the young persons, while the discontinuous pattern was frequently observed in the elderly patients. These findings suggest that the cerebral vascular resistance is more increased in the elderly patients than in the young persons. The cerebral blood flow pattern was classified into the following three types according to the continuity of the cerebral blood flow pattern: continuous, intermediate and discontinuous type, and the relation to the Continuous Index (CI), which was devised as an objective parameter of the continuity, was examined. The following CI figures were obtained: 110-200% in the young persons; in the elderly patients: continuous type, 120-185%; intermediate type, 85-135%; discontinuous type, 50-85%. From the above findings it is postulated that the Doppler ultrasonic technique is useful for the quantitative detection of cerebral arteriosclerosis, i.e., anticipation of cerebral vascular accidents, and for the discrimination between arteriosclerotic dementia and Alzheimer's disease.

Age Factors↗

Vascular renin-angiotensin system in two-kidney, one clip hypertensive rats.

The possible role of the renin-angiotensin system in the maintenance of hypertension in two-kidney, one clip hypertensive rats was studied. Plasma renin activity rose rapidly and markedly in association with the elevation of blood pressure and then decreased gradually, although blood pressure remained high. Renin activity in the lung, aorta, and mesenteric artery also increased with the development of hypertension and then decreased in a way similar to that of plasma renin activity at the chronic stage of hypertension. Plasma angiotensin converting enzyme activity did not change significantly until 16 weeks after unilateral renal artery clipping, whereas vascular angiotensin converting enzyme activity significantly increased at the chronic, but not the acute, stage of hypertension. In chronically renal hypertensive rats, 1-sarcosine, 8-isoleucine angiotensin II or enalapril, an angiotensin converting enzyme inhibitor, lowered the blood pressure and enalapril also lowered the angiotensin converting enzyme activity of vascular tissues. The constrictor effect of angiotensin I was greater in isolated arteries from chronically hypertensive rats than in those from age-matched normotensive rats. These results suggest that the vascular renin-angiotensin system plays an important role in the maintenance of two-kidney, one clip hypertension. Elevated vascular angiotensin converting enzyme activity appears to increase local production of angiotensin II, which results in vasoconstriction by acting directly and indirectly through adrenergic nerves on vascular smooth muscle.

Angiotensin II↗

Caudate hemorrhage.

Thirteen patients with caudate hemorrhage are described. All the hemorrhages were in the head of the caudate nucleus, and all the hemorrhages but one ruptured in the anterior horn of the lateral ventricle. In 9 patients, the hemorrhage was related to hypertension and the patients were older. In the other 4 patients, the hemorrhage resulted from rupture of an arteriovenous malformation (AVM) and the patients were under 40 years old. Clinical manifestations were nearly the same in both groups, suggestive of subarachnoid hemorrhage and including hemiparesis in most patients. In patients with hypertension, good recovery was obtained by conservative treatment and in those with ruptured AVMs, resection of AVMs through an anterior transcallosal approach may be safe and recommended.

Adult↗

Responsiveness to vasoconstrictor and dilator agents of senescent beagle cerebral arteries.

With advancing age from 2 to 12 years, contractions of isolated beagle cerebral arteries mediated by histamine H1 and serotonin receptors increased, whereas those induced by noradrenaline and angiotensin II did not differ. Relaxations by vasodilator substances, such as prostaglandin (PG) I2, isoproterenol, adenosine and K+ (5 mM), and by stimulation of vasodilator nerves in the adult and senescent beagle arteries did not significantly differ.

Adenosine↗

Endothelium-dependent changes in the response to vasoconstrictor substances of isolated dog mesenteric veins.

In dog mesenteric vein strips, contractions induced by histamine relative to those induced by 5 mM Ba++ were potentiated by removal of endothelium. The induced contractions were potentiated by AA861, a lipoxygenase inhibitor, and methylene blue, a guanylate cyclase inhibitor, to an appreciably greater extent in the strips with endothelium than in those with damaged endothelium. Indomethacin did not potentiate the contraction induced by histamine. Cimetidine potentiated the contraction in control strips and those without endothelium to a similar extent whereas chlorpheniramine suppressed the contraction. Contractile responses to acetylcholine, norepinephrine, serotonin and prostaglandin (PG) F2 alpha were not potentiated by removal of endothelium. It may be concluded that histamine activates histaminergic receptors, possibly H1 but not H2, in endothelial cells and results in a release of vasodilator substance produced by lipoxygenase, which accumulates cellular cyclic GMP and relaxes mesenteric veins. The H1 and H2 receptors in smooth muscle cells appear to be responsible for contractions and relaxations, respectively. Acetylcholine, norepinephrine, serotonin and PGF2 alpha do not seem to release vasodilator substances from endothelium in an amount sufficient to cause significant relaxations of venous smooth muscle.

Animals↗

Comparative study of proliferation of suckling and adult rat hepatocytes in primary culture in response to growth-stimulating factors.

The replicative responses of suckling and adult rat hepatocytes in primary culture to growth-stimulating factors were compared. By addition of L-proline alone, the [3H]-thymidine labeling of suckling rat hepatocytes was dramatically enhanced, but that of adult ones was not. Epidermal growth factor (EGF), insulin, triiodothyronine (T3) and glucagon also enhanced the labeling of suckling rat hepatocytes regardless of the presence or the absence of L-proline. On the other hand, in the absence of L-proline, only EGF enhanced the labeling of adult rat hepatocytes, and, in the presence of L-proline, insulin as well as EGF enhanced the labeling. In the presence of growth factors and L-proline, the number of suckling rat hepatocytes increased up to about 143%, whereas that of adult rat hepatocytes hardly increased. Thus, a remarkable difference in replicative responses to growth factors and L-proline was observed between suckling and adult rat hepatocytes in primary culture.

Aging↗

Artificial liver support for postoperative hepatic failure with anion exchange resin (BR-601).

An artificial liver support system for plasma exchange and plasma perfusion through BR-601 resin using a membrane separator was applied to 5 patients with postoperative liver failure. Percent absorption of total and direct bilirubin, and of bile acids were 77.1 +/- 6.4, 78.4 +/- 6.1, and 93.4 +/- 3.6%, respectively, when 250 ml of plasma was treated. Percent reductions in total and direct bilirubin, and in bile acids were 24.5 +/- 5.8, 25.5 +/- 5.8 and 30.9 +/- 8.5%, respectively. In contrast, percent reductions in total and direct bilirubin, and in bile acids by plasma exchange were 30.9 +/- 13.3, 34.5 +/- 12.5 and 24.2 +/- 8.5%, respectively. The coma grade was improved in 4 out of 5 cases, but unfortunately the patients did not recover. In conclusion, plasma perfusion through BR-601 resin is expected to play a promising role in artificial liver support systems because of its capacity to absorb bilirubin and bile acids.

Adult↗

Effects of food intake and various extrinsic hormones on portal blood flow in patients with liver cirrhosis demonstrated by pulsed Doppler with the Octoson.

In the fasting state the mean portal blood flow demonstrated by the pulsed Doppler system with the Octoson in liver cirrhosis (LC) patients (velocity (PV), 10.2 +/- 3.5 (mean +/- SD) cm/sec, 7.0 +/- 2.6 cm/sec/m2; flow (PF), 579 +/- 262 ml/min, 383 +/- 184 ml/min/m2 (n = 40)) was significantly lower than that in control subjects (PV, 21.2 +/- 5.2 cm/sec, 14.7 +/- 3.9 cm/sec/m2; PF, 966 +/- 344 ml/min, 667 +/- 220 ml/min/m2 (n = 40)). Food intake increased PV by 15% and PF by 15% in LC (n = 8) and increased PV by 56%, PF by 125% in controls (n = 8). Glucagon increased PV by 30% and PF by 52% in LC (n = 10) and increased PV by 50% and PF by 120% in controls (n = 8). Secretin increased PV by 44% and PF by 75% in LC (n = 9) and increased PV by 66% and PF by 142% in controls (n = 8). Vasopressin decreased PV by 42% and PF by 54% in LC (n = 9) and decreased PV by 48% and PF by 62% in controls (n = 8). Insulin, gastrin, and prostaglandin E1 had no effect in either group.

Adult↗

Long-term follow-up results of selective VIM-thalamotomy.

The authors report the results of a long-term follow-up study of the effects of the physiologically defined selective VIM (nucleus ventralis intermedius)-thalamotomy on tremor of Parkinson's disease in 27 patients and essential tremor in 16 patients. The follow-up period ranged from 3.25 to 10 years (mean 6.58 years). In 43 patients a total of 50 operations (including four bilateral operations and three reoperations) were carried out. The early (2 to 4 weeks after surgery) and late effects on the tremors were determined clinically and electromyographically. Fourteen parkinsonian cases were treated with minimal lesions (about 40 cu mm). Their late results were very similar to the early results: in 10, the tremors were completely abolished, three had a slight residual tremor, and one underwent reoperation 3 months after the first surgery. Eleven essential tremor cases were treated with minimal lesions. Six of these tremors were completely abolished, four patients had slight residual tremors, and one patient with a recurrence underwent reoperation 2 years after the initial surgery. In these 23 successful operations with minimal lesions (excluding two cases with reoperation), the tremor was abolished without discernible long-lasting side effects. The other 23 operations on 16 patients with Parkinson's disease (including one reoperation) and on seven with essential tremor (one of whom also had a minimal lesion on the other side) involved relatively large lesions. In this group, the surgery was successful in almost every case. It was concluded that radiographically and physiologically monitored selective VIM-thalamotomy for parkinsonian and essential tremor is effective even when lesioning is minimal. Moreover, the beneficial effect is maintained over a long period of time.

Adult↗