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Biomedical subjects

S Niimura

Publications and source records attributed to S Niimura.

53 records · Page 3Linked to original sources

Biochemical evidence for existence of immunoreactive renin in human prolactinoma tissue.

High activity of renin was demonstrated in human prolactinoma tissue. This activity was almost completely inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases. The specific activity of renin was 5.04 ng of angiotensin I generated/mg of protein per h, comparable to that of the pituitary tissue prepared from postmortem human subjects. The biochemical properties of the prolactinoma renin were generally similar to those of well-known kidney enzyme, such as molecular mass (Mr = 46,000), optimum pH (6.0), and glycoprotein nature. However, the isoelectric points (pI) of the prolactinoma renin (pI = 4.90, 5.04, 5.24 and 5.41) differed somewhat from those of plasma and kidney renins reported hitherto. These results indicate that true renin can be produced in human prolactinoma tissue.

Chromatography, Affinity↗

[A case of 21-hydroxylase deficiency and Bartter's syndrome associated with a balanced 6-9 translocation].

A 17-year-old female weighing 37 kg and 140 cm in height was referred to our hospital for evaluation of dwarfism and primary amenorrhea. She was delivered with 3350 g in weight and 50 cm in height after a ten month pregnancy without complications. No abnormal findings were revealed in physical appearance except critomegaly. Episodes of nausea, vomiting and dehydration were rare throughout her childhood, but she had a tendency to salt craving. At the age of 14, her height was 140 cm. On admission, her physical development was markedly retarded for her age, except external genitalia. Diffuse pigmentations on the trunk and extremities were observed. Her blood pressure was normal (112/62 mm Hg). Serum potassium concentration was 2.9 mEq/L. Arterial-blood gas analysis revealed metabolic alkalosis. Both of renin activity (PRA) and aldosterone concentration (PAC) in plasma at rest were markedly elevated to 15.5 ng/ml/h and 107.1 ng/dl, respectively. The plasma concentrations of pregnenolone (1449 ng/dl), progesterone (178 ng/dl), 17-OH-pregnenolone (1613 ng/dl), 17-OH-progesterone (180 ng/dl), dehydroepiandrosterone (3706 ng/dl), androstendione (824.6 ng/dl) and testosterone (900 ng/dl) were high, whereas deoxycorticosterone (15.7 ng/dl), corticosterone (0.65 microgram/dl) and cortisol (6.8 micrograms/dl) were within normal limits. Urinary 17-KS excretion showed high levels between 65.7 and 109.4 mg/day, while urinary 17-OHCS excretion was normal (5.7-7.0 mg/day). Vascular response to angiotensin II (A-II) was attenuated. Distal fractional chloride reabsorption was decreased (CH2O/CH2O+CCl = 0.62, normal: 0.92 +/- 0.04). Moderate hyperplasia of the juxtaglomerular cells was demonstrated in biopsy specimen of the kidney. Cytogenetic studies showed a 46, XX chromosome constitution with translocation of the long arm of chromosome 6 to the short arm of chromosome 9. Her mother as well as younger brother and sister, whose electrolytes and arterial-blood gas analysis showed normal values, had chromosomes with the same translocation. Treatment with dexamethasone (2 mg/day) reduced every adrenal steroids to normal range, but PRA and PAC remained high levels. Furthermore, neither hypokalemic alkalosis nor vasoreactivity to exogenous A-II was improved. Indomethacin (75 mg/day) decreased urinary excretion of prostaglandin E2 from a high level of 738.4 ng/day to 433.4 ng/day and normalized metabolic alkalosis. Vascular response to A-II was moderately improved. However, serum potassium remained low.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Demonstration and characterization of angiotensin-converting enzyme in human pituitary tissue.

High activity of angiotensin-converting enzyme was demonstrated in human pituitary tissue. This activity required the presence of chloride ion and was almost completely inhibited by a specific converting enzyme inhibitor captopril (10 nM), indicating that the activity measured is indeed angiotensin-converting enzyme. The specific activity of the enzyme was 1.68 +/- 1.20 nmol hippuric acid generated mg of protein-1 min-1 (mean +/- SD, for 11 specimens). The biochemical features of the enzyme were closely related to the well-characterized human lung converting enzyme, such as molecular weight (290,000), optimum pH (8.0-8.5), the presence of glycoprotein residues, and dependence on chloride ion concentration. These results provide definitive evidence for the presence of angiotensin-converting enzyme in human pituitary tissue.

Chlorides↗

Characterization of vascular permeability-increasing component isolated from solid tumors and the effect of highly polymerized dextran sulfate on its activity.

Increase in vascular permeability is usually seen at the growth site of a tumor implant in murine dermal tissue. Increased vascular permeability was inducible by the subcutaneous injection of a solid tumor extract rich in protein precipitable at 20-50% saturation of ammonium sulfate. The vascular permeability-increasing activity of the tumor extract was reducible in the presence of highly polymerized dextran sulfate (DS-500) which showed a strong anticomplementary activity, but not by other substances such as dextran sulfate with a low molecular weight, non-sulfated dextran, chondroitin sulfate or heparin. As the tumor extract includes gamma-globulins in aggregated or bound form and adsorbs complements, it is probable that the aggregated gamma-globulins increase vascular permeability by triggering the complement activation system in the skin. DS-500 might antagonize the process.

Ammonium Sulfate↗

Growth experiment of Hantaan virus in A549 cells: an attempt to improve the immunofluorescent antibody technique for hemorrhagic fever with renal syndrome.

An assay method for the infectivity of Hantaan virus, a causative agent of HFRS (hemorrhagic fever with renal syndrome), was developed by the use of IFA (immunofluorescent antibody technique). With the aid of this method, the growth characteristics of Hantaan virus, 76-118 strain, were followed in A549 cells. At a maximal MOI (multiplicity of infection) of 1.6 VAIU (viral antigen-inducing units) per cell, the conventionally available value, plateau level potencies of the viral antigen and virus infectivity were attained at eight and ten days postinfection, respectively, and most of the infective virus produced accumulated in the culture fluids of infected cells. When infections were defined with MOI values in terms of VAIU per cell, development of the viral antigen was highly consistent and followed a given pattern of kinetics. Based on these findings, a protocol for preparation of the viral antigen in IFA was presented, wherein spot culture and FBS treatment were emphasized as effective procedures to minimize non-specific staining.

Animals↗

Antihypertensive effect of a new calcium channel blocker, FK 235, in essential hypertension.

The antihypertensive effect of a new calcium channel blocker (FK 235) were evaluated in 10 patients with mild-to-moderate essential hypertension. The study consisted of 4 weeks of placebo and 12 weeks of the drug, 2 to 4 mg twice a day. Overall systolic and diastolic blood pressures (mean +/- SE) were reduced from 173 +/- 4 to 158 +/- 2 mm Hg (p less than 0.001) and from 97 +/- 2 to 89 +/- 1 mm Hg (p less than 0.001), respectively, with a dose of 5.6 +/- 0.7 mg/day. No relevant changes in heart rate, body weight, and plasma levels of renin activity and aldosterone concentration were observed. No side effects were encountered during the therapy. Our data indicate that the novel active calcium channel blocker can be used as a safe, effective and well tolerated antihypertensive for the treatment of essential hypertension.

Adult↗

[Evidence for the existence of inactive renin in the rat brain. Part II. Distribution of inactive renin in the brain of spontaneously hypertensive rats].

Inactive renin in the brain of spontaneously hypertensive rat was investigated. The results are as follows. Treatment with either trypsin or glandular kallikrein of the brain tissue extract caused a rapid and apparent increase in the renin activity at either 0 or 27 degrees C. The molecular weight of the active renin was estimated to be 41,000 or 50,000 daltons, while that of the trypsin-activatable inactive renin was found to be 44,000 or 57,000 daltons on a column chromatography with Sephadex G-100. The contents of the active renin was the highest in the hypothalamus, followed by the striatum, thalamus, midbrain, medulla oblongata, cerebral cortex and cerebellum, while the contents of the trypsin-activatable inactive renin was the highest in the hypothalamus, followed by the striatum, thalamus, cerebellum, midbrain, cerebral cortex and medulla oblongata. These results suggest that inactive renin(s) exist in the brain of spontaneously hypertensive rat. It seems likely that the brain renin-angiotensin system is modulated by the conversion of inactive to active renin(s), which, in turn, plays at least in part a role in the blood pressure regulation through generation of angiotensin II in spontaneously hypertensive rats.

Animals↗

Immunoreactive renin in human brain: distribution and properties.

Readily detectable levels of renin activity were demonstrated in the human brain. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific action of proteases such as cathepsin D. The pineal gland was found to be the richest source of renin followed by the pituitary, hypothalamus and hippocampus. The substantia nigra, caudate nucleus, putamen and thalamus contained moderately high concentrations of renin. The brain renins from pineal and pituitary glands shared some biochemical features with well-known kidney renin, such as molecular weight (46,000 daltons for pineal renin; 37,000-45,000 daltons for pituitary renin), optimum pH (6.0-7.0), the presence of trypsin activatable inactive renin, and a glycoprotein nature. However, the electrofocusing pattern of renin from pituitary tissue (pI = 4.43, 5.77) differed from that of plasma and kidney enzymes heretofore reported, a discrepancy which could be interpreted as evidence for the endogeneous synthesis of renin in the brain tissue. Furthermore, a high activity of immunoreactive renin was found in human neuroblastoma tissue. The biochemical characteristics of the neuroblastomal renin were generally similar to the known properties of kidney renin in many respects, providing evidence of the presence of the renin-angiotensin system within human neuronal cells.

Brain↗

Characterization of tumor-induced inflammation and the effect of some anti-inflammatory drugs on the increased vascular permeability.

The vascular bed in a murine dermal tissue responded to inoculated tumor cells by two-phased changes in the vascular permeability. The initial increase in the vascular permeability was seen in an early stage (1 to 3 day post tumor cells inoculation), and the inflammation was sensitive to glutathione (GSH). Glucocorticoids reduced the increased vascular permeability, but neither acetylsalicylic acid nor indomethacin did. The later vascular response was produced by a growing solid tumor in a continuous mode beginning at 5th to 10th day post inoculation. The degree of the increased vascular permeability in this chronic phase was in direct proportion to the wet weight of the solid tumor, and the inflammation was insensitive to glutathione. Glucocorticoids reduced the increased vascular permeability, but neither acetylsalicylic acid nor indomethacin did. The action of glucocorticoids on the tumor-induced vascular hyper-permeability was discussed in connection with a tumor factor possibly responsible for the vasoexudation.

Animals↗

[Histochemical demonstration of proteins, lipids and polysaccharides in Japanese monkey oocytes].

A histochemical study of proteins, lipids and polysaccharides was carried out in the oocytes of Japanese monkey (Macaca fuscata) during development of follicles. There were a small number of protein granules reactive to acrolein-Schiff in the cytoplasm of oocytes from primordial, secondary and vesicular follicles, while there were no lipid droplets, granules of neutral polysaccharides or acid polysaccharides in the cytoplasm. Proteins reactive to acrolein-Schiff, neutral polysaccharides reactive to periodic acid-Schiff and acid polysaccharides stainable with alcian blue were observed in the zona pellucida of the oocytes of secondary and vesicular follicles. The zona pellucida contained sudanophilic lipids composed of neutral fats and lipoids, besides the proteins and polysaccharides.

Animals↗

Acute effects of the new oral angiotensin converting enzyme inhibitor 1-(D-3-acetylthio-2-methylpropanoyl)-L-prolyl-L-phenylalanine (Alacepril) in essential hypertension.

In 15 patients with mild-to-moderate essential hypertension a new orally active angiotensin converting enzyme inhibitor, 1-(D-3-acetylthio-2-methylpropanoyl)-L-prolyl-L-phenylalanine (Alacepril), was administered with a single oral dose of 50 mg to evaluate its antihypertensive effect. Following Alacepril plasma angiotensin converting enzyme (ACE) activity was inhibited by approximately 75% within 2 h. Plasma renin activity increased slightly whereas plasma levels of aldosterone decreased significantly. Blood pressure fell markedly not only in patients with high renin levels but also in those with low renin levels. Nevertheless, the magnitude of blood pressure reduction was correlated with the pre-treatment plasma renin values (r = -0.602, p less than 0.05 systolic, r = -0.667, p less than 0.01 diastolic). No relevant changes in pulse rate was observed. These findings demonstrate that in essential hypertension the novel orally active ACE inhibitor Alacepril exerts marked antihypertensive effect, which may offer a new effective approach to treatment of hypertension.

Administration, Oral↗

Biochemical identification of renin in human pheochromocytoma.

A high activity of renin was demonstrated in human pheochromocytoma tissue. This activity was inhibited by specific antibody raised against human renal renin, indicating that it was not due to the nonspecific actions of proteases such as cathepsin D. The specific renin shared some biochemical features with well-known kidney renin, such as molecular weight (47,000 daltons), optimum pH (6.0), the presence of trypsin-activatable inactive renin, and glycoprotein nature. However, the isoelectrofocusing pattern of renin from the pheochromocytoma differed from that of kidney and plasma renins hitherto reported, a discrepancy which could be interpreted as evidence for endogenous synthesis of the enzyme. Furthermore, angiotensin converting enzyme activity was found in the tissue. Since pheochromocytoma is considered to be of neural crest origin, these results provide biochemical and immunological evidence for the presence of the renin-angiotensin cycle within human neuronal cells.

Adolescent↗

[Evaluation of amputation techniques for the study of limb regeneration in the newt and toad].

A comparison between forelimb amputations through the radius-ulna and the humerus was made in the adult newt, Cynops pyrrhogaster pyrrhogaster and the young toad, Xenopus laevis. Newts regenerated their forelimbs after the amputations and the new parts resembled the old in structure and function. Toads regenerated their forelimbs incompletely after the amputations. The new parts lacked joints and fingers showing a simply elongate pattern. The effect of re-amputation of exposed bone on the regeneration was evaluated in the adult newt. A left forelimb was amputated through the humerus and the exposed bone which protruded from the cut surface due to the relationships of the soft tissues, was then re-amputated a few minutes later. A right forelimb of the same individual was simply amputated without re-amputation of the exposed bone. Newts regenerated both forelimbs simultaneously. The new parts resembled the old in structure and function.

Amputation, Surgical↗

Histochemical studies of delta5-3beta-, 20lapha- and 20beta-hydroxysteroid dehydrogenases and possible progestagen production in hamster eggs.

Hamster eggs at various developmental stages were studied histochemically fro the presence of delta5-3beta-hydroxysteroid dehydrogenase (HSD) (pregnenolone as the substrate and NAD as the cofactor), 20alpha-HSD (20alpha-hydroxypregn-4-en-3-one and NADP) and 20 beta-HSD (20beta-hydroxypregn-4-en-3-one and NAD). All three enzymes were absent from ovarian eggs but were demonstrated in unfertilized and fertilized eggs up to the blastocyst stage. The activities varied only slightly.

Animals↗

Thermal laser-assisted angioplasty of renal artery stenosis for renovascular hypertension.

Percutaneous transluminal laser-assisted angioplasty of a renal artery stenosis was performed in a 16-year-old woman with renovascular hypertension. The stenotic portion of the renal artery was predilated by delivering Nd-YAG laser energy to the terminal tip of a laser catheter. Although the luminal diameter did not increase sufficiently with laser angioplasty alone, it allowed passage of the balloon catheter and subsequent successful balloon angioplasty. Immediately after dilatation, the patient's blood pressure fell to normal, and plasma renin activity decreased. There were no serious complications. Thermal laser angioplasty seems to be an effective adjunct technique for the treatment of severe renal artery stenosis which does not allow initial passage of a balloon catheter.

Adolescent↗