[Aging and endocrine function: analysis of the physiological profile from laboratory database].
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Adolescent↗
Biomedical subjects
K Ichihara
Publications and source records attributed to K Ichihara.
MCl-176, a novel calcium channel blocker, attenuates the ischemic myocardial acidosis induced by coronary artery occlusion in dogs.
The effect of MCl-176 [2-(2,5-dimethoxyphenylmethyl)-3-(2-dimethylaminoethyl)-6- isopropoxy-4(3H)-quinazolinone hydrochloride], a novel calcium channel blocker, on ischemic myocardial acidosis was studied in the dog heart, in which the left anterior descending coronary artery was partially occluded for 90 min (partial occlusion). Myocardial pH (measured by a micro glass pH electrode) was about 7.60 in the nonischemic normal heart. The myocardial pH decreased rapidly in response to partial occlusion, and reached the steady state of about 6.85 within 30 min (i.e., the myocardial [H+] increased after partial occlusion). Saline or drug was injected i.v. 30 min after partial occlusion, and the drug effect was observed till the end of partial occlusion. Myocardial [H+], that had been increased by partial occlusion, restored slightly after the saline injection, and the restoration was about 30% 60 min after the injection. MCl-176 increased this spontaneous restoration of myocardial [H+] with a decrease in blood pressure and heart rate; the restoration induced by 0.1 mg/kg of MCl-176 was 74% 60 min after the injection. Even in the paced heart, MCl-176 (0.1 mg/kg) attenuated the ischemia-induced myocardial acidosis. Propranolol (1 mg/kg) also attenuated the myocardial acidosis, the restoration being 82%. These results indicate that MCl-176 attenuates the myocardial acidosis during ischemia as does propranolol, and that the mechanism of action of MCl-176 is not due primarily to a decrease in heart rate.
Acidosis↗
[Studies on tissue PO2 and biochemical analysis of the skeletal muscle of legs with chronic arterial occlusive diseases].
Measurements of maximum tissue PO2 during 100% O2 inhalation (PtO2max) and biochemical analysis of the skeletal muscle were performed in 3 legs without ischemia and 14 legs with chronic arterial occlusive disease requiring amputation. There were significant good correlations between PtO2max and levels of pH, lactate, enzymes (CPK, LDH, Aldolase) and ATP in the skeletal muscle with ischemia. In regions in which PtO2max was below 10mmHg, ischemic changes in the muscle were considered to be irreversible. On the contrary, primary wound healing was obtained in regions with 40mmHg or more of PtO2max. Measurements of the PtO2max of the ischemic muscles provided much useful information concerning the reversibility of muscle ischemia and for decision of the amputation level.
Adenosine Triphosphate↗
Specific stimulation of steroid 5 alpha-reductase solubilized from rat liver microsomes by endogenous phosphatidylserine.
Dilauroylphosphatidylcholine caused a marked increase in progesterone 5 alpha-reductase activity solubilized from rat liver microsomes, whereas naturally occurring phosphatidylcholines from biological sources as well as dioleoylphosphatidylcholine had not effect on the activity. Therefore, the stimulatory effect of phospholipids normally found in rat liver microsomes was examined. The lipid extracts were prepared from the fraction which was freed from 5 alpha-reductase activity by DEAE-cellulose chromatography, and found to exhibit a strong stimulatory effect. The lipid extracts were then separated into phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine by chromatography on silicic acid column and preparative thin-layer plate. Among these endogenous phospholipids, only phosphatidylserine stimulated the 5 alpha-reductase, suggesting that the lipid requirement is specific for phosphatidylserine in steroid 5 alpha-reductase from liver microsomes.
Animals↗
1-Acyl-sn-glycerol-3-phosphate acyltransferase in maturing safflower seeds and its contribution to the non-random fatty acid distribution of triacylglycerol.
A 20,000 X g particulate preparation isolated from maturing safflower seeds catalyzed the acylation of 1-acyl-sn-glycerol 3-phosphate with acyl-CoA to form phosphatidate. The specific activity of the reaction exceeded 200 nmol min-1 mg protein-1. Although this preparation was also capable of catalyzing the acylation of sn-glycerol 3-phosphate with acyl-CoA, the hydrolysis of phosphatidate, and the acylation of 1,2-diacylglycerol, phosphatidate was the only major product when the preparation was incubated with 1-acyl-glycerol-3-P and acyl-CoA. The enzyme responsible for this phosphatidate synthesis, 1-acyl-glycerol-3-P acyltransferase, showed a strict acyl-CoA specificity. The relative order of specificity for acyl-CoA was linoleoyl = oleoyl greater than palmitoleoyl greater than elaidoyl greater than cis-vaccenoyl greater than stearoyl = palmitoyl. This observation strongly suggests that the fatty acid composition of position 2 in phosphatidate synthesized in vivo primarily depends on both the acyl-CoA specificity of the 1-acyl-glycerol-3-P acyltransferase and the fatty acid composition of the acyl-CoA pool in the cell. Thus, the absence of saturated fatty acids at position 2 of safflower triacylglycerol may be explained in terms of the acyl-CoA specificity of the 1-acyl-glycerol-3-P acyltransferase. The fatty acid moiety esterified at position 1 of glycerol-3-P also affected the effectiveness of the reaction. The 1-acyl-glycerol-3-P acyltransferase utilized 1-acyl-glycerol-3-P molecular species in the following order of effectiveness: linoleoyl = oleoyl greater than palmitoyl. With a rise in incubation temperature, the initial rates of acylation with unsaturated acyl-CoA species increased more rapidly than those for saturated acyl-CoA species. A similar tendency was observed for saturated and unsaturated acyl acceptors. These data suggest that affinity of the acyltransferase for substrates may vary in response to changes in temperature, and that 1-acyl-glycerol-3-P acyltransferase may be involved in the alteration of the individual fatty acid compositions at positions 1 and 2 of glycerolipids in tissues grown at different temperatures. Based on these findings, further metabolism of 1-acyl-glycerol-3-P acyltransferase products could be the major factor determining the non-random distribution of fatty acids in safflower triacylglycerol.
1-Acylglycerol-3-Phosphate O-Acyltransferase↗
Effect of nadolol, a beta-adrenoceptor blocking agent, on myocardial metabolism in the dog ischaemic heart.
The effect of nadolol at a dose of 1 mg kg-1, i.v. on the ischaemic myocardial metabolism has been examined in the dog. Ischaemia was induced by ligating the left anterior descending coronary artery for 3 min, and nadolol was injected 5 min before ligation. Ischaemia caused myocardial metabolic changes; it decreased energy charge potential and inhibited glycolytic flux through phosphofructokinase reaction. Pretreatment with nadolol lessened the decrease in energy charge potential and the inhibition of glycolytic flux being caused by ischaemia. Nadolol may have a beneficial effect on the ischaemic myocardium.
Adenine Nucleotides↗
Long term results of transsphenoidal adenomectomy in patients with Cushing's disease.
As part of an ongoing series, 100 patients with Cushing's disease underwent transsphenoidal operations. Pituitary adenomas were confirmed in 93 patients, and initial remission was achieved in 86 (92%) of them. Hypercortisolemia was not corrected in 7 patients, and in 4 this was due to invasive adenomas. These patients were subjected to irradiation, medical treatment, or both after operation. Only 7 of the 100 patients had no pituitary adenoma found at operation, and they obtained no clinical remission even after partial or subtotal hypophysectomy. Follow-up review, with an emphasis on endocrinological studies, was performed on these patients for a mean period of 38 months. Seventy-eight patients were in long term remission after operation and had restoration of noncorticotropic hormone secretion as well as pituitary-adrenal function. Recurrence was noted in 8 patients after 19 to 82 months in remission. In all of these patients, pituitary adenomas were verified by reoperation and no case of corticotrophic cell hyperplasia was noted. We conclude that late recurrence of Cushing's disease may occur after adenoma removal and is due to the regrowth of adenoma cells left behind in the peritumoral tissue at the first operation. In view of the overall remission rate, transsphenoidal adenomectomy is considered a highly effective treatment for Cushing's disease.
Adenoma↗
Effects of nicorandil and other antianginal drugs on myocardial pH in the ischemic dog heart.
The effects of nicorandil and other antianginal drugs on the pH of ischemic myocardium were examined in dogs anesthetized with pentobarbital. The myocardial pH was measured with a micro glass pH electrode placed in the inner layers of the area of myocardium perfused by the left anterior descending coronary artery (LAD). The myocardium (LAD area) was made ischemic by partially occluding the LAD so that only about one-third of the normal blood flow was allowed to perfuse the tissue. The period of LAD occlusion was 90 min. By 30 min, the partial occlusion had produced a decrease in myocardial pH (about 0.5 U) which lasted until the end of occlusion. The acidosis in the myocardium induced by LAD partial occlusion was metabolic acidosis. The experimental drugs were injected intravenously 30 min after the LAD was occluded. Nicorandil (50 micrograms/kg), nitroglycerin (20 micrograms/kg), and diltiazem (100 micrograms/kg) moderately restored the myocardial H+ concentrations induced by LAD occlusion; propranolol (1 mg/kg) and sotalol (5 mg/kg) markedly restored these concentrations. It was concluded that all five experimental drugs improved ischemic myocardium; nicorandil, nitroglycerin, and diltiazem only moderately counteracted the increased myocardial H+ concentrations produced by LAD occlusion, whereas propranolol and sotalol markedly returned myocardial pH close to normal levels.
Acidosis↗
[From clinical tests to etiology: analysis of clinical features. New diagnostic criteria from a clinical database and its application. A new type of thyroid binding-protein abnormality].
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Alpha-Globulins↗
[A sudden death occurring in genital Paget's disease with cardiac and systemic metastases].
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Death, Sudden↗
Enzyme immunoassay of free triiodothyronine in serum.
In this new solid-phase antibody enzyme immunoassay for free triiodothyronine (FT3) in serum, beta-D-galactosidase conjugated to triiodothyronine is used. Results are uninfluenced by physiological concentrations of thyroxin-binding globulin or albumin. Results correlate well with those determined by equilibrium dialysis (r = 0.95). The mean CVs within and between assays were 6.1 and 9.5%, respectively. The measurable range of FT3 in serum is 0.7 to 26 ng/L; the normal reference interval is 1.9 to 8.9 ng/L. Concentrations of FT3 in serum of patients with hyperthyroidism were high; those of patients with hypothyroidism were within normal limits or low, and those of patients with congenitally decreased or increased TBG were within the normal range. In normal pregnant women, concentrations of FT3 as determined by radioimmunoassay correlated with those of albumin, declining as pregnancy progressed, but FT3 values determined by the proposed method or equilibrium dialysis were within the normal range and did not change during pregnancy.
Adult↗
Some properties of progesterone 5 alpha-reductase solubilized from rat liver microsomes.
The experiments described in this paper were undertaken to examine the requirements of NADPH-cytochrome c reductase and phosphatidylcholine for hepatic steroid 5 alpha-reduction, previously proposed by Golf and Graef (Golf, S. W. and Graef, V. (1978) J. Steroid Biochem. 9, 369-371). To determine how NADPH-cytochrome c reductase participates in hepatic 5 alpha-reductase activity, antibodies against the purified NADPH-cytochrome c reductase were added to 5 alpha-reductase preparation solubilized from rat liver microsomes. Whereas both NADPH-cytochrome c reductase and progesterone 16 alpha-hydroxylase in the preparation were inhibited by the antiserum, the inhibitory effect on 5 alpha-reductase activity was not observed. In addition, chromatography of the polyethylene glycol fraction active in 5 alpha-reduction on DEAE-cellulose resulted in the complete separation of 5 alpha-reductase activity from NADPH-cytochrome c reductase activity. Unlike NADPH-cytochrome c reductase, phosphatidylcholine increased the activity of the partially purified 5 alpha-reductase about 2.5 fold. Phosphatidylserine also enhanced the activity to an extent identical for phosphatidylcholine. Phosphatidic acid and lysophosphatidylcholine were stimulatory to lesser extents.
Animals↗
Inhibition of ischemia-induced subcellular redistribution of lysosomal enzymes in the perfused rat heart by the calcium entry blocker, diltiazem.
Effect of diltiazem on subcellular distribution of lysosomal enzymes, high-energy phosphate metabolism and mechanical function in the ischemic heart was studied. Ischemia was induced by lowering the afterload pressure of the perfused working rat heart. The activities of cathepsin D, beta,N-acetylglucosaminidase and acid phosphatase were determined in the nonsedimentable and sedimentable fractions after centrifugation of the tissue extract to assess the subcellular distribution of lysosomal enzymes. After ischemia, decreases in the mechanical function and the tissue level of high-energy phosphates were observed. In addition, ischemia caused subcellular redistribution of lysosomal enzymes from the lysosomes to the cytoplasm. Reperfusion of the ischemic heart did not restore the mechanical function and the level of high-energy phosphates completely. Diltiazem (2.21 X 10(-6), 1.11 X 10(-5) and 2.21 X 10(-5) M) was provided for the heart 5 min before the onset of ischemia. Diltiazem preserved high-energy phosphates in the ischemic heart, and inhibited the subcellular redistribution of lysosomal enzymes being caused by ischemia, depending on its concentration. Reperfusion after ischemia with diltiazem recovered the mechanical function that had been decreased by ischemia. These results may indicate that diltiazem can protect the myocardium against ischemic damage.
Acetylglucosaminidase↗
Some properties of the fatty alcohol oxidation system and reconstitution of microsomal oxidation activity in intestinal mucosa.
This paper describes the metabolism of fatty alcohols by microsomal and cytosolic fractions from intestinal mucosa. Microsomes of rabbit intestinal mucosa had a high activity of [1-14C]dodecanol oxidation as did those of liver. The intestinal cytosolic fraction also exhibited oxidation activity to a lesser extent than the microsomes did. The reaction product was determined as lauric acid using thin-layer chromatography. Laurylaldehyde was detected as another product, when semicarbazide was added to the incubation system. Cyclodextrins exhibited a stimulation effect similarly to bovine serum albumin on the microsomal activity. We have compared the stimulatory effects of dimethyl-beta-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin and alpha-cyclodextrin, which decrease in that order. Effects of NAD+ and dodecanol concentrations, pH and pyrazole on microsomal activity were compared with those on cytosolic activity. Dodecanol oxidation activity was solubilized and reconstituted with a fatty alcohol dehydrogenase and a fatty aldehyde dehydrogenase separated from the intestinal microsomes. These findings indicate that both the dehydrogenases participate in microsomal oxidation of fatty alcohols to fatty acids with fatty aldehydes as intermediates in the reaction.
Alcohol Oxidoreductases↗
Purification of aldehyde dehydrogenase reconstitutively active in fatty alcohol oxidation from rabbit intestinal microsomes.
This work presents the purification and further characterization of the aldehyde dehydrogenase reconstitutively active in fatty alcohol oxidation, from rabbit intestinal microsomes. Microsomal aldehyde dehydrogenase was solubilized with cholate and purified by using chromatography on 6-amino-n-hexyl-Sepharose and 5'-AMP-Sepharose. The purified enzyme migrated as a single polypeptide band with molecular weight of 60,000 on SDS-polyacrylamide gel. By gel filtration in the presence of detergent, its apparent molecular weight was estimated to be 370,000. In the detergent-free solution, in contrast, it had a much higher molecular weight, indicating its association in forming large aggregates. The pH optimum was 9.0 when pyrophosphate buffer was used. The enzyme was active toward various aliphatic aldehydes with more than three carbons. The Km value for substrate seemed to decrease with increase in the chain length. The microsomal aldehyde dehydrogenase was not affected by disulfiram and MgCl2, which were, in contrast, highly inhibitory towards the activity of the cytosolic aldehyde dehydrogenase separated from intestinal mucosa.
Aldehyde Oxidoreductases↗
Effects of the intravenous administration of magnesium sulfate on corrected serum calcium level and nephrogenous cyclic AMP excretion in normal human subjects.
The effect of intravenous magnesium sulfate infusion on corrected serum calcium level and parathyroid function assessed by determination of nephrogenous cAMP (NcAMP) excretion were studied in normal human subjects. Significant hypermagnesemia induced by the magnesium sulfate infusion for 120 minutes was accompanied by a gradual and progressive decrease in the corrected serum calcium level. NcAMP excretion fell rapidly, reaching a nadir between 60 and 120 minutes after the infusion began, and after that rose above the baseline excretion. Urinary calcium excretion gradually increased, reaching a peak between 120 and 180 minutes after the infusion began and then gradually decreased. Since magnesium was given as the sulfate, it is not clear whether these changes were attributable to magnesium or sulfate or both. As a control study, we performed intravenous sodium sulfate infusion. The sodium sulfate infusion caused slight hypocalcemia, slight hypercalciuria, and a significant increase in NcAMP excretion. These findings indicate that the hypocalcemia and the hypercalciuria caused by the magnesium sulfate infusion is mainly due to the effect of magnesium, and that the decrease in NcAMP excretion during the infusion is due to the effect of magnesium alone. We conclude that the hypocalcemia caused by the magnesium sulfate infusion is mainly due to the renal calcium loss, and that the inhibition of parathyroid function caused by hypermagnesemia may be only partially involved in the early phase of this hypocalcemia.
Adult↗
New indices for thyroid functional status, hormone binding, and peripheral hormone metabolism. Principal component analysis of 24,000 clinical data.
Principal component analysis of three thyroid function tests, thyroxine (T4), 3,5,3'-triiodothyronine (T3), and T3 uptake (T3U), was done using 24,000 data obtained from patients with a wide range of pathophysiologic conditions related to the thyroid. The three component scores were obtained as follows: Z1 = 2.62 square root T4 + 0.63 square root T3 + 3.18 square root T3U - 32.43; Z2 = 0.91 square root T4 + 0.24 square root T3 - 4.68 square root T3U + 20.14; and Z3 = 3.94 square root T4 + 0.95 square root T3 + 0.18 square root T3U - 1.53 (T4 micrograms/dL, T3 ng/dL, T3U%). The first component (Z1) represents an apparent axis to the direction of thyroid functional status. It provides a new metabolic index putting conventional free T4 and free T3 indices together. The second component (Z2) was found to be a sensitive indicator of abnormal hormone binding. It showed a close correlation with serum concentration of thyroxine-binding globulin. The third component (Z3) represents the degree of T3 predominance over T4. Computation of these scores will facilitate the diagnosis of atypical cases in which hyper-or hypothyroidism is complicated by abnormal peripheral hormone binding and/or metabolism.
Humans↗
Occurrence of cytochrome P-450 with prostaglandin omega-hydroxylase activity in rabbit placental microsomes.
The microsomes of placenta and uterus from pregnant rabbits have been found to catalyze the omega-hydroxylation of PGE1, PGE2, PGF2 alpha, and PGA1 as well as the omega- and (omega-1)-hydroxylation of palmitate and myristate in the presence of NADPH. These activities were greatly inhibited by carbon monoxide, indicating the involvement of cytochrome P-450. The apparent Km for PGE1 was 2.38 microM and 2.1 microM with the placental and uterus microsomes, respectively. Cytochrome P-450 has been solubilized with 1% cholate from the placental microsomes, and partially purified by chromatography on 6-amino-n-hexyl Sepharose 4B, DEAE-Sephadex A-50 and hydroxylapatite columns. The partially purified cytochrome P-450 efficiently catalyzed the omega-hydroxylation of various prostaglandins such as PGE1, PGE2, PGF2 alpha, PGD2, and PGA1 in a reconstituted system containing NADPH-cytochrome P-450 reductase, cytochrome b5, and phosphatidylcholine. The reconstituted system also hydroxylated palmitate and myristate at the omega- and (omega-1)-position, but could not hydroxylate laurate. These catalytic properties resemble those of a new form of cytochrome P-450 highly purified from the lung microsomes of progesterone-treated rabbits (Yamamoto, S., Kusunose, E., Ogita, K., Kaku, M., Ichihara, K., and Kusunose, M. (1984) J. Biochem. 96, 593-603). This type of cytochrome P-450, viz., cytochrome P-450 with high prostaglandin omega-hydroxylase activity may play a role in the regulation of prostaglandin levels in pregnancy.
Animals↗