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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 757 records · Page 42Linked to original sources

Human trabecular meshwork organ culture.

Human trabecular meshwork obtained from postmortem eyes was maintained in organ culture condition up to 12 weeks. The explants were dissected into specimens of three different sizes. Types 1 and 2 specimens were larger than 4 mm square and 1 mm thick, and type 3 specimens were about 1 mm3. Each specimen was placed in a depression made in the center of an agar block and the block was placed in a plastic culture dish. The space between the agar block and the culture dish was filled with liquid medium consisting of MEM Eagle supplemented with 10% fetal bovine serum, 10% chick embryo extract and 200 U/ml penicillin G. Afterwards, the explant was incubated in 5% CO2 with 100% humidity. Types 1 and 2 specimens maintained a normal appearance on electron microscopy during the entire 12 weeks of culture, while type 3 specimens showed marked cellular activation and cell loss soon after explantation. Morphometric studies regarding cell number in sections for light microscopy obtained from types 1 and 2 specimens revealed good preservation of trabecular cells during the 12 weeks of culture. Our culture system may be useful in investigating the direct effects produced on human trabecular meshwork by photocoagulation and various agents, for example anti-glaucoma drugs, steroids and viscoelastic materials.

Cadaver↗

[Clinical studies on sultamicillin in pediatrics].

Sultamicillin (SBTPC) fine granule was given orally to 15 children with acute bacterial infections including 4 with acute pharyngitis, 5 with acute tonsillitis, 2 each with acute bronchitis and urinary tract infections, and 1 each with acute pneumonia and cervical purulent lymphadenitis. Good to excellent clinical responses were obtained in all of the 15 patients and bacterial eradication of all 4 strains found in these cases. Loose stool was observed in 1 case. From the above clinical results, it appears that SBTPC is a useful antibiotics for the treatment of pediatric patients with various bacterial infections.

Administration, Oral↗

Third coronary artery: its development and function.

The third coronary artery arises directly from the aorta and forms anastomoses by the fetal stage. In this study, we used the stereoscope to investigate 622 normal human hearts (from fetuses to adults) and determine the origin of the third coronary artery and variations in positions of origin, bearing in mind the age. The orientation of the third coronary artery orifice is classified into 3 types: 10, 9 and 8 o'clock. There is not significant relative incidence in the 3 types. In connection with multiple third coronary artery orifices, pathologic hearts had a higher incidence than normal hearts but there is no relation to age. Regarding the size of the third coronary artery orifice, a normal heart is smaller than a pathologic heart. The existence of multiple third coronary artery orifices and the fact that pathologic hearts have a higher incidence than normal hearts suggest that the third coronary artery develops and contributes to the collateral circulation after birth.

Adolescent↗

Different distribution of two types of angiotensin II-generating enzymes in the aortic wall.

Dog, monkey and human aortic tissues contained two distinct types of angiotensin II-generating enzymes; angiotensin converting enzyme (ACE) and chymostatin-sensitive angiotensin II-generating enzyme (CAGE). Endothelium, media and adventitia of canine thoracic aortae were separated using collagenase digestion, and determined for their ACE and CAGE activity. ACE activity was assayed by hippuryl-His-Leu cleavage. CAGE activity was estimated with ANG I as substrate in the presence of inhibitors of ACE and angiotensinases. His-Leu, the common product of both enzyme reactions, was fluorimetrically quantified after o-phthalaldehyde condensation. ACE localized mainly in endothelium, while CAGE distributed predominantly in adventitia. Similar results were obtained with human and monkey aortae. Such a contrasting distribution may indicate the distinct functional role of these two enzymes.

Aorta↗

The involvement of central cholinergic mechanisms in cardiovascular responses to intracerebroventricular and intravenous administration of thyrotropin-releasing hormone.

Intracerebroventricular (i.c.v.) administration of thyrotropin-releasing hormone (TRH) in a range from 0.1 to 100 micrograms induced a dose-related increase in blood pressure in conscious rats, whereas TRH-free acid (TRH-OH) and histidyl-proline diketopiperazine (His-Pro-DKP), metabolites of TRH, did not. The blood pressure responses to intravenous (i.v.) injection of 5 mg/Kg TRH were similar to those induced by TRH (i.c.v.). Pretreatment with atropine (50 micrograms, i.c.v.) significantly reduced the pressor effect of TRH administered through either route. Hemicholinium-3 (50 micrograms, i.c.v.), an inhibitor of choline uptake, also prevented the increase in blood pressure induced by TRH (10 micrograms, i.c.v.). These results indicate that both centrally and peripherally administered TRH have pressor effects that are mediated by central cholinergic mechanisms, probably by activating cholinergic neurons.

Animals↗

Effect of various barbituric acid derivatives on survival of functional hepatocytes from adult rats in primary culture.

Eighteen barbituric acid (BA) derivatives and three structurally related chemicals (non-BA-derivatives) were tested for their potency in supporting survival of functional hepatocytes from adult rats in primary culture. Of the 18 BA derivatives, nine drugs showed excellent maintenance effect on hepatocyte survival and function. Although four BA derivatives were also effective, their potency was relatively lower. The remaining five BA derivatives and three structurally related chemicals exhibited no maintenance effect. Thus, a correlation was found between the BA derivative structure and the potency for supporting hepatocyte survival in primary culture. The dose response curves of hepatocyte survival were generally biphasic in shape, as a function of BA derivative concentration. The optimum concentrations for observing the morphological and biochemical effects of the BA derivatives differed from each other. The maintenance of hepatocytes was attained only in the continuous presence of the BA derivatives in the medium. The nine excellent BA derivatives efficiently prevented hepatocytes from morphological degeneration which was observed in the control cultures. The surviving hepatocytes in the presence of these BA derivatives showed higher albumin secretion and retained higher basal levels of tyrosine aminotransferase (TAT) activity for at least 2 weeks in primary culture, as compared with control. Furthermore, the addition of dexamethasone (10 microM) caused a 2- to 4-fold induction of TAT activity for at least 2-weeks in primary culture.

Albumins↗

Synthesis of barbituric acid derivatives and their effect on survival of functional hepatocytes from adult rats in primary culture.

Ten barbituric acid (BA) derivatives were synthesized and tested for their potency for supporting survival of functional hepatocytes from adult rats in primary culture. Of the 10 BA derivatives, 7 compounds (C-2, 3, 4, 5, 6, 9, and 10) efficiently supported hepatocyte survival for at least 2 wks in primary culture. Especially C-5, 6, and 9 showed excellent efficiency for such action. The optimum concentrations of the BA derivatives for observing the morphological and biochemical effects differed from each other. The maintenance of hepatocytes was attained only in the continuous presence of the BA derivatives in the medium. The morphologic features of hepatocytes surviving in the presence of the BA derivatives resembled those of hepatocytes 24 h after inoculation. The surviving hepatocytes secreted remarkably large amounts of albumin into the culture media. Tyrosine aminotransferase (TAT) activity was higher in the 1-wk-old cultures treated with C-5, 6, and 9 than in the freshly isolated hepatocytes. The addition of dexamethasone (10 microM) caused a 1.7 to 2.1-fold induction in TAT activity. The basal levels of TAT activity and the induction rates increased in the cultures treated with C-5 and 6 from Week 1 to 2 of primary culture.

Albumins↗

Amyloid of neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence.

The presence of abundant intraneuronal amyloid in the form of neurofibrillary tangles (NFT) in the brains of Guamanian parkinsonism-dementia patients and the absence of extraneuronal amyloid in the form of vascular amyloid deposits or senile plaques permit the purification of NFT without contamination with extraneuronal amyloid. Thus, we have isolated and determined the amino acid sequence of the polypeptide subunit of the amyloid fibrils of these NFT and describe their ultrastructure. The NFT, which consist of single and paired helical filaments, similar to those of Alzheimer disease, and occasionally triple helical filaments, are composed of multimeric aggregates of a polypeptide of 42 amino acids (A4 protein). The relative molecular mass of the subunit protein, 4.0-4.5 kDa, is the same as the molecular mass of the amyloid of NFT, of the amyloid plaque cores, and of vascular amyloid deposits in Alzheimer disease and Down syndrome; the sequence of 15 amino acid residues at the N-terminus of the amyloid fibrils in the NFT of Guamanian parkinsonism-dementia is identical to that of the amyloid of NFT, amyloid plaque cores, and cerebrovascular deposits in Alzheimer disease and Down syndrome. Furthermore, the heterogeneity, or variation in polypeptide length, of the N-terminus of the amyloid of Guamanian parkinsonism-dementia is the same as in Alzheimer disease and Down syndrome. Our observations indicate that the brain amyloids of these diseases have a common subunit protein, which would also indicate a common pathogenesis.

Aged↗

Senescent beagle coronary arteries in response to catecholamines and adrenergic nerve stimulation.

With advancing age from 2 to 12 years, relaxations induced by norepinephrine and epinephrine were suppressed or reversed to contractions in large and medium-size coronary arteries isolated from beagles. Norepinephrine-induced contractions in the senescent beagle arteries treated with propranolol were greater than those in the young beagle arteries and were inhibited by prazosin but not by yohimbine. Relaxant responses to isoproterenol were less in the arteries from old beagles than in the young beagle arteries. The magnitude of relaxations induced by norepinephrine and epinephrine was greatest in small arteries from old beagles, followed by medium and large arteries, in that order. Transmural electrical stimulation tended to produce a contraction in the old beagle arteries and a relaxation in the strips from young beagles. It appears that alpha 1 adrenoceptor function increases with advancing age in beagle coronary arteries of large and medium sizes, and beta receptor function declines. Vasoconstriction mediated by alpha 1 receptors is postulated to be related inversely to the distance from the coronary orifice in senescent beagles, and vice versa with vasodilatation mediated by beta receptors.

Aging↗

Elevated vascular angiotensin converting enzyme in chronic two-kidney, one clip hypertension in the dog.

The possible role of the vascular angiotensin converting enzyme (ACE) in the development of two-kidney, one clip (2-K, 1C) hypertensive dogs was studied in different blood vessels. Vascular ACE activity per mg protein differed in a variety of blood vessels; the activity appeared to vary inversely with the outer diameter of arteries. The systemic blood pressure in mongrel dogs increased after partial occlusion of the left renal artery, and the hypertension lasted for 8 months. Plasma renin activity (PRA) was raised only for the first 4 weeks after the operation and then returned to the original level in the chronic stage of hypertension. Plasma ACE activity did not alter during the experimental period. In contrast, ACE activities in the jejunal, pulmonary and renal arteries, aorta, lung and cerebral cortex, significantly increased in the chronic hypertensive stage (8 months after occlusion). The production of angiotensin II (ANG II) from ANG I was significantly greater in isolated arteries from 8-month hypertensive dogs than in those from normotensive dogs when assessed by the contractile responses to ANG I and ANG II. These results indicate that acceleration by increased vascular ACE activity of the production of ANG II in the vascular wall may contribute to the maintenance of hypertension in the chronic stage of 2-K, 1C hypertensive dogs having normal PRA and plasma ACE activity.

3-Mercaptopropionic Acid↗

The interaction of pancuronium and vecuronium with cardiac muscarinic receptors.

The interaction of vecuronium, a monoquaternary analogue of pancuronium, with the cardiac muscarinic receptors in canine hearts was investigated in vitro by [3H] QNB binding assay and compared with that of pancuronium. Both pancuronium and vecuronium, which are nicotinic antagonists of competitive types, inhibited the binding of [3H] QNB to cardiac muscarinic receptors with values of IC50 of 5.41 X 10(-7) mol/l and 3.97 X 10(-6) mol/l respectively. According to the Kd and Bmax values on the Scatchard plot, pancuronium, while not influencing the number of receptors, had a 3-fold greater inhibitory effect than vecuronium on the affinity of the muscarinic receptors. The KI values of vecuronium and pancuronium showed that pancuronium had a 7.3-fold greater affinity with the receptors than vecuronium. We concluded that vecuronium had a direct inhibitory action on the binding of [3H] QNB to the canine heart muscarinic receptors, but this action was much weaker than pancuronium.

Animals↗

Reliability of cochlear microphonics in clinical electrocochleography.

A study was made on the reliability of cochlear microphonics (CM) recorded in clinical electrocochleography (ECochG) by the transtympanic electrode technique. In normal-hearing subjects, the CM shift increased as the frequency was lowered at the same sound pressure, and as the sound pressure was lowered at the same frequency. The CM shift for the frequencies from 8 to 0.5 kHz was greater as the sound pressure was lowered. The above results suggest that clinical ECochG CM responses may well reflect the potential of the cochlea.

Acoustic Stimulation↗

Hypotensive effect of SA446, an angiotensin converting enzyme inhibitor, in 2-kidney, 1-clip renal hypertensive and normotensive dogs.

Hypotensive effects of SA446, an angiotensin converting enzyme (ACE) inhibitor, and effects on the renin-angiotensin system were evaluated in conscious normotensive and 2-kidney, 1-clip renal hypertensive dogs. SA446 (1 mg/kg, p.o.) remarkably inhibited the pressor response to angiotensin (Ang) I between 1 and 6 hr after the administration in normotensive dogs. SA446 significantly decreased blood pressure at 10 mg/kg, p.o., in normotensive dogs. During repeated administration of SA446 (100 mg/kg/day, p.o.) for 13 weeks, the blood pressure was lowered, and the pressor response to Ang I and plasma ACE activity were strongly inhibited. ACE activities in the aorta and kidney were also inhibited. Plasma renin activity and plasma Ang I concentration increased by repeated SA446 application, while plasma aldosterone concentration decreased. The hypotensive effect of SA446 (5 mg/kg, p.o.) was more potent in 2-kidney, 1-clip renal hypertensive dogs than in normotensive dogs. SA446 had longer inhibitory effects on the pressor response to Ang I and more potent hypotensive effects than captopril. The hypotension caused by SA446 appears to be associated mainly with an inhibition of ACE in plasma and also in the vascular wall.

3-Mercaptopropionic Acid↗

Possible role of vascular angiotensin converting enzyme in the genesis of hypertension.

This study was designed to evaluate changes in angiotensin converting enzyme (ACE) activity in 2-kidney, 1-clip renal hypertensive dogs. Blood pressure increased and remained elevated for eight months after partial clamping of the left renal artery. Plasma renin activity was increased for one month after surgery, but then returned to the pre-clamping level. SA-446, a potent ACE inhibitor, reduced blood pressure in 8 M-hypertensive dogs. Plasma ACE activities was not altered during the course of hypertension, but vascular ACE activities in the pulmonary and mesenteric arteries and the aorta were significantly increased in 8 M-hypertensive dogs. These results may indicate that ACE plays an important role in the maintenance of chronic phase of 2-kidney, 1-clip renal hypertension and that suppression of vascular ACE activities might be a mechanism underlying the hypotensive effect of ACE inhibitors.

Animals↗