Improvement of renal function in AA type amyloidosis by prolonged treatment with dimethylsulfoxide (DMSO).
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Amyloidosis↗
Biomedical subjects
K Aoyagi
Publications and source records attributed to K Aoyagi.
[My experience with uterine myoma. A patient's description].
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Female↗
Feeding-related activity of glucose- and morphine-sensitive neurons in the monkey amygdala.
Feeding-related neuronal activity of monkey amygdalar glucose-sensitive and morphine-sensitive cells was investigated during a task that required bar-pressing to obtain food. Both glucose-sensitive and morphine-sensitive cells, located mostly in the centromedial part of the amygdala, decreased firing during the bar-press period more often than insensitive cells. Naloxone attenuated the decrease in activity during the bar press period. The results suggest involvement of these glucose- and morphine-sensitive cells in the control of food acquisition behavior.
Amygdala↗
Renal kallikrein in diabetic patients with hypertension accompanied by nephropathy.
We measured the 24-h excretion of urinary kallikrein in 27 patients with Type 2 (non-insulin-dependent) diabetes and in 10 normal control subjects. Mean (+/- SD) kallikrein excretion in diabetic patients with nephropathy (6.2 +/- 2.4 naphthyl units (NU)/day, n = 13) was significantly lower than in control subjects (12.8 +/- 3.4 NU/day, p less than 0.01) and in diabetic patients without nephropathy (9.4 +/- 3.4 NU/day, n = 14, p less than 0.05). Kallikrein excretion in hypertensive diabetic patients with nephropathy (5.1 +/- 1.6 NU/day, n = 8) was significantly lower (p less than 0.05) than in normotensive patients with nephropathy (8.3 +/- 2.1 NU/day, n = 5). There were no significant differences in kallikrein excretion rate (24-h excretion of urinary kallikrein/24-h creatinine clearance) among control subjects (9.9 +/- 4.3 NU/ml), diabetic patients with (9.0 +/- 3.2 NU/ml) and without (9.3 +/- 3.5 NU/ml) nephropathy. However, kallikrein excretion rate in hypertensive diabetic patients with nephropathy (7.7 +/- 3.3 NU/ml) was significantly lower (p less than 0.05) than in normotensive diabetic patients with nephropathy (11.8 +/- 2.0 NU/ml, n = 10). Respective basal and post-stimulated (with intravenous furosemide 40 mg plus 60 min ambulation) plasma aldosterone concentrations measured in control subjects and in hypertensive diabetic patients with nephropathy were similar and increased to the same extent in the 2 groups (5.5 +/- 3.2 versus 5.3 +/- 3.2 and 9.3 +/- 2.6 versus 10.5 +/- 3.4 ng/ml), although the respective plasma renin activity tended to be lower in diabetic patients than in control subjects (0.7 +/- 0.6 versus 1.3 +/- 0.9 and 1.8 +/- 1.8 versus 3.0 +/- 2.6 ng-1 . ml-1 . h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Plasma renin activity, active and inactive renin concentrations, and their responses to beta 1-adrenoceptor blockade with metoprolol in hyperthyroidism.
Plasma renin activity (PRA), plasma renin concentration (PRC), inactive renin concentration (IRC) and total renin concentration (TRC) were measured in 31 normal controls and in 8 patients with hyperthyroidism. TRC was determined as angiotensin I generated with sheep renin substrate after an acid activation of plasma. The angiotensin I of non-acidified plasma was expressed as PRC. IRC was calculated as TRC minus PRC. The mean values for PRA, PRC, IRC and TRC were significantly (P less than 0.05 to P less than 0.01) higher in the hyperthyroid patients than in the normal or euthyroid controls. The administration of a beta 1-adrenergic blocker, metoprolol (120 mg/day for 14 days), produced a significant (P less than 0.05 to P less than 0.01) fall in levels of T4, PRA and TRC, and reduced the active renin ratio calculated from PRC/TRC significantly (P less than 0.025), as compared to the pretreatment values. Our observations support the idea that the higher PRA in hyperthyroidism is due to an increased secretion of renin. Furthermore, the results may indicate that the conversion of inactive to active renin is accelerated in hyperthyroidism, possibly by an increased sympathetic activity.
Adult↗
Appearance and accumulation of c(4) carbon pathway enzymes in developing maize leaves and differentiating maize a188 callus.
Regenerating maize A188 tissue cultures were examined for the presence of enzymes involved in C(4) photosynthesis, for cell morphology, and for (14)C labeling kinetics to study the implementation of this pathway during plant development. For comparison, sections of maize seedling leaves were examined. Protein blot analysis using antibodies to leaf enzymes showed a different profile of these enzymes during the early stages of shoot regeneration from callus from the closely-coordinated profile observed in seedling leaves. Pyruvate orthophosphate dikinase (PPDK) (EC 2.7.9.1) and phosphoenolpyruvate carboxylase (PEPC) (EC 4.1.1.31) were found in nonchlorophyllous callus while ribulose 1,5-bisphosphate carboxylase (RuBPC, EC 4.1.1.39) and malic enzyme, NADP-specific (ME-NADP) (EC 1.3.1.37) were not detectable until later.Enzyme activity assays showed the presence of ME-NADP as well as PEPC and PPDK in nonchlorophyllous callus. However, the activities of ME-NADP and PEPC had properties similar to those of the enzymes from C(3) leaves and from etiolated C(4) leaf tissues, but differing from the corresponding enzymes in the mature leaf.Immunoprecipitation of in vitro translation products of poly(A)RNA extracted from embryoid-forming callus showed both the 110 kilodalton precursor to chloroplast PPDK and the 94 kilodalton polypeptide. Therefore, the chloroplast tye of PPDK mRNA is present prior to the appearance of leaf morphology.Analysis of the labeled products of (14)CO(2) fixation by nonchlorophyllous calli indicated beta-carboxylation to give acids of the tricarboxylic acid cycle, but no incorporation into phosphoglycerate. With greening of the callus, some incorporation into phosphoglycerate and sugar phosphates occurred, and this increased in shoots as they developed, although with older shoots the increase in beta-carboxylation products was even greater. Analysis of enzyme levels in young leaf sections by protein blot and of (14)C-labeling patterns in the present study are in general agreement with enzyme activity determinations of previous studies, providing additional information about PPDK levels, and supporting the model proposed for developing young leaves.These results suggest that maize leaves begin to express C(4) enzymes during ontogeny through several stages from greening and cell differentiation as seen in the callus and then shoot formation, and finally acquire capacity for full C(4) photosynthesis during leaf development concomitant with the development of Kranz anatomy and accumulation of large amounts of enzymes involved in carbon metabolism.
Journal Article↗
Appearance and accumulation of c(4) carbon pathway enzymes in developing wheat leaves.
Soluble protein has been extracted from sections of wheat leaves, from base to tip, and the content of several key enzymes of photosynthetic carbon assimilation in each section has been determined by the protein blot method. In the first leaf, ribulose 1,5-bisphosphate carboxylase (RuBPC) (EC 4.1.1.39) in the basal 0 to 1 centimeter section is about 12% the level in the tip section, whereas phosphoenolpyruvate carboxylase (EC 4.1.1.31) is present in small amounts in the basal section and does not change much in the tip. Pyruvate orthophosphate dikinase (PPDK) (EC 2.7.9.1) first appears in the 4 to 6 centimeter section and increases gradually with development to 10-fold in the tip. Malic enzyme, NADP-dependent (EC 1.3.1.37) also appears in the 4 to 6 centimeter section but remains low to the tip.Fixation of (14)CO(2) by wheat leaf base sections resulted in 42% of total incorporation into malate and aspartate, indicating beta-carboxylation, whereas in the tip section these labeled compounds were only 8% of the total. Although the amount of PPDK in wheat leaves is only 1 to 3% of that in maize leaves, this C(3) PPDK may have a limited role in photosynthesis leading to formation of C(4) compounds. The possibility of a further role, similar to that in C(4) plants, but for intracellular carbon transport in wheat leaves is discussed. The presence of malic dehydrogenase, NADP-specific (EC 1.1.1.82) in wheat leaf chloroplasts was shown, a necessary though not sufficient condition for such a proposed role. Assuming each of the four enzymes associated with C(4) carbon transport were fully active in vivo during photosynthesis, PPDK would still be rate limiting, even in the leaf tip where its activity is maximal. Possible evolutionary and breeding implications are discussed.
Journal Article↗
Variation in amounts of pyruvate, orthophosphate dikinase, and some other enzymes of the c(4) pathway in some wheat species.
First leaves and flag leaves of the wheat species Triticum aestivum cv Anza (6x), T. boeoticum Boiss (2x) L. were examined for content of pyruvate, orthophosphate dikinase (PPDK), phosphoenolpyruvate carboxylase (PEPC), and ribulose 1,5-bisphosphate carboxylase (RuBPC) by protein blot analyses using antibodies to maize leaf enzymes and by activity assays. In agreement with previous reports, the amount of RuBPC per mesophyll cell was about 3 times more in the hexaploid species, T. aestivum, than in the diploid species, T. boeoticum, both in first leaves and in flag leaves. In contrast, the level of PPDK polypeptide was nearly 3-fold higher per unit leaf area in the first leaf and 63% higher in the flag leaf of this diploid species compared to this hexaploid species. There was no significant difference in the levels of polypeptide and enzyme activity of PEPC between diploid and hexaploid wheat. Despite this significantly greater level of PPDK in the diploid species, the actual amount of PPDK could still supply only a limited amount of the enzyme activity necessary to provide phosphoenolpyruvate (PEP) for any putative intracellular C(4) carbon shuttle providing carbon to RuBPC. Thus, this difference in enzyme amount could not by itself account for the reported high rates of net photosynthesis at high light intensity in T. boeoticum. Together with reported anatomical differences between the diploid and hexaploid species, however, this biochemical difference may be of physiological importance.
Journal Article↗
Elastase-type activity in human radial artery in patients with chronic renal failure.
To elucidate the nature of the abnormality of elastin metabolism in arteriosclerosis, we determined the elastase-type activity in the human radial artery of patients with chronic renal failure due to glomerular disease and diabetes. Elastase-type activity was determined by HPLC analysis of the hydrolyzed products of succinyl-trialanine-4-nitroanilide, a sensitive synthetic substrate for elastase. Three kinds of hydrolyzed products, (L-Ala)2-NA, L-Ala-NA and NA, were found after incubation of the substrate with human radial artery in the presence of amastatin (an inhibitor of aminopeptidases). We assumed the activity that liberates NA to be an elastase-type activity because purified human aorta elastase liberates NA from the substrate. The pH optima of the human artery and rat aorta activities were 6.0 and 6.8, respectively. The elastase activity in human radial artery and rat aorta was inhibited by diisopropyl phosphofluoridate, a serine protease inhibitor, and by elastatinal, an elastase inhibitor. The elastase-type activity in the radial artery of patients with chronic renal failure was significantly lower than that of the control group, and the decrease was especially marked in the patients with juvenile onset diabetes. These results suggest that the elastin metabolism is abnormal in the radial artery in diseases that tend to cause atherosclerosis.
Adult↗
Active oxygen in methylguanidine synthesis.
Methylguanidine (MG), a toxin reported in uremia, is thought to be a product of creatinine oxidation. This study is designed to demonstrate the role of active oxygen in the oxidation of creatinine under conditions compatible with those found in uremia. MG synthesis is moderately stimulated by the superoxide radical derived from 3 mM hypoxanthine and 0.015 units/ml xanthine oxidase and inhibited by the addition of superoxide dismutase. This is increased markedly by the addition of 0.05% hydrogen peroxide and augmented to about 56,000 times the control rate in the presence of hydroxyl radicals derived from the reaction of 10 mM FeSO4 and 0.05% hydrogen peroxide. In addition, MG synthesis is inhibited by the addition of sorbitol, lactulose or ethanol, the scavengers of hydroxyl radicals. These results indicate that creatinine can be oxidized to MG by various species of active oxygen and that one of the mechanisms of MG synthesis is such oxidation. MG, therefore, may be a useful indicator of peroxidation in vivo.
Creatinine↗
Renal effects of nicardipine, a calcium entry blocker, in hypertensive type II diabetic patients with nephropathy.
We studied the renal effects of nicardipine, a calcium entry blocker, in eight patients with essential hypertension (group A, WHO I or II), six hypertensive type II diabetics with mild-to-moderate nephropathy (group B, urinary albumin 200-789 mg/day), and six hypertensive type II diabetics with severe or advanced nephropathy (group C, urinary albumin 1,596-4,300 mg/day). The patients received an intravenous dose of nicardipine hydrochloride (0.5 mg) or saline placebo in a random order. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured by means of thiosulfate sodium and p-aminohippurate, respectively, during the 30 min after the nicardipine or saline injection. Blood pressures were serially monitored during the study. Nicardipine reduced both systolic and diastolic blood pressures significantly (P less than .05 to .01) at all measurement periods in all study groups compared with the respective placebo. Nicardipine increased RBF (P less than .01), GFR (P less than .05), and urinary Na+ excretion (P less than .01) and decreased total renal vascular resistance (P less than .01) in groups A and B, but these parameters remain unchanged in group C. The filtration fraction remained unaltered in all groups. The results indicate that nicardipine has several favorable renal effects with a concomitant hypotensive action in hypertensive type II diabetics with mild-to-moderate nephropathy, as observed in patients with uncomplicated essential hypertension, and the renal pharmacological responsiveness appears to be related to the severity of nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Purification and characterization of a human kidney neutral endopeptidase that hydrolyzes succinyl trialanine-4-nitroanilide and biologically active peptides.
An enzyme hydrolyzing succinyl trialanine-4-nitroanilide was extracted from human kidney homogenate and purified by means of gel filtration on Sepharose CL-4B, anion-exchange chromatography on DEAE-Sepharose CL-6B and affinity chromatography on carbobenzoxy-L-Ala-L-Ala-D-Ala-polylysine-agarose. The purified enzyme consists of a single peptide, and its molecular weight was estimated to be about 125 000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme cleaved the substrate at the bond between succinyl dialanine and alanine-4-nitroanilide and showed a Km value of 2.1 mM at the optimal pH of 8.0. The activity was increased by Ca2+ and Mg2+, but was inhibited by phosphoramidon and ethylenediaminetetraacetic acid. The enzyme cleaved the oxydized insulin B chain, angiotensinogen tetradecapeptide, angiotensin I, angiotensin II, angiotensin III, [Sar1,Ala8]-angiotensin II, bradykinin, des-Pro2-bradykinin, Leu5-enkephalin, Met 5-enkephalin, [D-Ala2,Met5]-enkephalinamide and [D-Ala2-Met5]-enkephalin, but did not cleave [D-Ala2,D-Leu5]-enkephalin. The bonds on the amino side of the hydrophobic amino acids of the peptides were cleaved by the enzyme.
Calcium↗
Elastase--does this enzyme play any role in bladder cancer invasion?
Elastase activity in bladder cancer tissue and normal bladder epithelium was assayed with succinyl trialanine paranitroanilide (Suc-Ala3-NA), a synthetic substrate of elastase. Elastase in the tissue extract liberated paranitroanilide (NA) from Suc-Ala3-NA and coexistant endopeptidases produced alanine-NA and dialanine-NA. These products were detected by high performance liquid chromatography. All activities of elastase and endopeptidases in bladder cancer tissues from 20 patients are significantly higher than those in 17 normal bladder epithelia. In 20 bladder cancer cases evaluated, the relation between the activities of elastase and endopeptidases and the background factors of each bladder cancer case was examined. There was a significantly different activity of elastase between the superficial bladder cancer group (less than or equal to T1) and the invasive group (T2 less than or equal to). Elastase is assumed to play an important role in cancer invasion.
Carcinoma, Transitional Cell↗
Pyruvate, pi dikinase in bundle sheath strands as well as in mesophyll cells in maize leaves.
Mesophyll protoplasts and bundle sheath strands were isolated from maize leaves. Light microscopic observation showed the preparations were pure and without cross contamination. Protein blot analysis of mesophyll and bundle sheath cell soluble protein showed that the concentration of pyruvate orthophosphate dikinase (EC 2.7.9.1) is about one-tenth as much in the bundle sheath cells as in mesophyll cells, but about eight times greater than that found in wheat leaves, on the basis of soluble protein. Phosphoenolpyruvate carboxylase (EC 4.1.1.31) was barely detectable in the bundle sheath cells, while ribulose-1,5-bisphosphate carboxylase (EC 4.1.1.39) and NADP-dependent malic enzyme (EC 1.3.1.37) were exclusively present in the bundle sheath cells and were absent in the mesophyll cells. Whereas pyruvate, Pi dikinase was previously considered localized only in mesophyll cells of C(4) plants, these results clearly demonstrate the presence of appreciable quantities of the enzyme in the bundle sheath cells of the C(4) species maize.
Journal Article↗
Synthesis and uptake of cytoplasmically synthesized pyruvate, pi dikinase polypeptide by chloroplasts.
Polyadenylated RNA was isolated from maize leaves and translated in vitro. In agreement with a previous report by others, we found among the translation products a 110-kilodalton pyruvate orthophosphate dikinase (PPDK) precursor that is about 16 kilodaltons larger than the polypeptide isolated from cells. This maize PPDK precursor polypeptide was taken up from the translation product mixture by intact spinach chloroplasts and yielded a mature PPDK polypeptide (94 kilodaltons). The uptake and processing support the proposal that the extra 16-kilodalton size of the polypeptide from in vitro translation of maize leaf mRNA represents a transit sequence which is cleaved after its entry into chloroplasts. Moreover, these results provide additional evidence that in vivo in maize leaf cells PPDK polypeptide is synthesized in the cytoplasm and is transported into the chloroplasts.Location of PPDK in C(3) plant leaves was investigated by immunochemical analysis. Intact chloroplasts were isolated from leaves of spinach, wheat, and maize. A protein blot of stromal protein in each case gave rise to bands corresponding to authentic PPDK polypeptide. This result indicates that PPDK is present in chloroplasts of C(3) plant leaves as it is in the case of C(4) plants.
Journal Article↗
Biosynthesis of methylguanidine in isolated rat hepatocytes and in vivo.
To clarify the organ in which methylguanidine is synthesized, high doses of creatinine, which is known to stimulate the synthesis of methylguanidine, were administered to male Wistar rats intraperitoneally. Various tissues of the rats were frozen by a freeze clamp method before and 1, 2 and 3 h after injection, and methylguanidine was determined by high-pressure liquid chromatography using 9,10-phenanthrenequinone for fluorometric determination. We found evidence that the liver, kidney, lung, muscle, red blood cells and gut flora synthesize methylguanidine. In addition, we measured the synthesis of methylguanidine in isolated hepatocytes prepared from normal rats following the addition of creatinine, arginine and guanidinoacetic acid to the incubation medium. Synthesis of methylguanidine was observed only in those incubations which contained creatinine, and was dependent on the concentration of creatinine in the media and on the incubation period. Isolated rat hepatocytes also synthesized guanidine in the presence of guanidinoacetic acid. These results indicate that the liver is one of the organs which synthesize methylguanidine and also that creatinine is the precursor.
Animals↗
Prevalence of hypertension in diabetes mellitus--its relation to diabetic nephropathy.
The prevalence of hypertension was studied in 374 patients with non-insulin dependent diabetes mellitus (NIDDM) and in 1197 non-diabetic controls. The diagnosis of hypertension was made when the mean systolic pressure of three measurements on different occasions was 151 mmHg or greater, or the mean diastolic pressure was 91 mmHg or greater. The prevalence was 42.8% in the diabetics and 17.8% in the controls. It showed a significant difference over age 31 (p less than 0.05). Proteinuria (p less than 0.001), abnormal ECG (p less than 0.01), hyperlipidemia (p less than 0.05) and hypertensive or sclerotic changes of the retina (p less than 0.001) were more frequently observed in the diabetics than in the controls. Hypertension was found in 71% of those with proteinuria, 48% with diabetic retinopathy, 61% with abnormal ECG and 54% with hyperlipidemia in the diabetics. The incidence of proteinuria was 22.8% in the diabetic hypertensives and was 8.3% in the non-diabetic hypertensives (p less than 0.001). 24 subjects out of 119 diabetics, who were normotensive at their initial visits, became hypertensive within 10 years (N-H), and 95 remained normotensive (N-N). 38% of N-H showed proteinuria already on their initial examinations and 3% of N-N did. 73% of those who showed proteinuria on their initial examination became hypertensive and 13% of those who were free from proteinuria did (p less than 0.001). The results suggest that diabetic nephropathy plays an important role in developing hypertension in diabetics.
Adult↗
[Synthesis of methylguanidine by active oxygen, with special reference to the significant role of hydroxyl radical].
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Creatinine↗