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Biomedical subjects

F Ikeda

Publications and source records attributed to F Ikeda.

At least 73 records · Page 4Linked to original sources
PubMed1984

Plasma carcinoembryonic antigen and acinar cell carcinoma of the pancreas.

Seventeen patients with histologically proven pancreatic cancers were studied in order to clarify the relationship of histologic types to plasma carcinoembryonic antigen (CEA) values. Two cases with marked elevation of plasma CEA values having 6100 ng/ml and 2500 ng/ml, respectively, disclosed histologically acinar cell carcinoma and mixed acinar and ductal cell carcinoma, respectively. Despite of massive hepatic metastases, the other 15 cases with ductal cell carcinoma, including 3 cases with cystadenocarcinoma, adenoacanthoma, and undifferentiated pancreatic cancer, respectively, showed normal or very modest elevation of plasma CEA values. No correlation was obtained between plasma CEA values and several biochemical tests. Two patients with marked elevation of plasma CEA value revealed strong staining in the cancerous areas of the pancreas by using a peroxidase-antiperoxidase staining technique. These findings suggest that acinar cell carcinoma of the pancreas may contribute to increase the circulating plasma CEA value.

Adenocarcinoma↗
PubMed1983

Collagenase activity in the granulocytes of patients with various liver diseases.

Studies were conducted on collagenase activity on peripheral granulocytes of patients with various liver diseases. Total collagenase activity increased significantly in chronic active hepatitis (CAH) and in liver cirrhosis (LC), and, in these disorders, it correlated with the extent to which hepatic fibrosis has progressed. Active collagenase activity increased in CAH, but no differences from normal controls were found in other liver diseases. These results suggest that total collagenase may reflect the degree of hepatic fibrosis, and that active collagenase may be related to chronic active hepatitis lesions.

Adult↗
PubMed1983

The target portion of acetaminophen induced hepatotoxicity in rats: modification by thiol compounds.

In order to determine the target portion of acetaminophen-induced hepatotoxicity, 750 mg per kg of body weight of acetaminophen was administered to male Wistar strain rats with or without the pretreatment of thiol compounds. In the liver, glutathione content decreased throughout the observation periods, and glutathione S-transferase initially, and later adenosine triphosphatase decreased, followed as elevations of aminotransferases and ornithione carbamoyltransferase in serum. The pretreatment of thiol compounds could not restore hepatic enzyme activities, but partially hepatic glutathione content and serum enzyme elevations. Although distinct time lag existed in biochemical alterations in the liver, hepatic glutathione content was significantly correlated solely with hepatic glutathione S-transferase. The mechanism of acetaminophen hepatotoxicity was discussed from the aspect of biochemical events in cytosol and membrane structure in hepatocytes. The mechanism of acetaminophen induced hepatotoxicity has been extensively investigated, and the hepatotoxicity seems to be related to the toxic metabolites generated by biotransformation process (Gillette et al., 1974, Mitchell et al., 1976). Since the toxic metabolites are conjugated with glutathione (GSH), it is generally accepted that when the hepatocellular GSH content has critically depleted, the metabolites seem to react with hepatocyte macromolecules and/or to produce lipid peroxidation, resulting in biochemical and structural changes leading to cell death (Black, 1980). A hepatotoxic dose of labelled acetaminophen was found throughout the liver and the highest concentration was found in centrilobular area, where considerable disruption and vacuolation of the plasma membrane and of the endoplasmic reticulum also occurred (Jollow et al., 1973, Chiu and Bhakthan, 1978). However remarkably little impairment of several enzyme systems in microsome, such as cytochrome P450 content, arylhydrocarbon hydroxylase and glucuronyl transferase has been reported (Thorgeirsson et al., 1976, Chiu and Bhakthan, 1978: Willson and Hart, 1977, Yamada et al., 1981). To elucidate the exact mechanism of acetaminophen hepatotoxicity, we observed time related biochemical alterations of hepatic GSH content, some marker enzymes in hepatocyte subfractions and serum enzymes. The present results indicated that acetaminophen reduced hepatic GSH content, followed as depletions of glutathione S-transferases (GSTs) and finally adenosine triphosphatase (ATPase), associated with elevations of serum enzymes.

Acetaminophen↗
PubMed1982

Enhancement of intracellular 5-phosphoribosyl 1-pyrophosphate levels as a major factor in the 6-azauridine-induced stimulation of carbamoyl phosphate synthesis in mouse spleen slices.

Brief exposure to 6-azauridine stimulates the production of carbamoyl phosphate for de novo pyrimidine biosynthesis in vitro in slices of haematopoietic spleen from anaemic mice (preceding paper). In studies of the underlying mechanism for this response we turned our attention to changes in the level of substrates and effectors for carbamoyl-phosphate synthetase II. Intermediates of the orotic acid pathway and 6-azauridine had little effect on the synthetase activity in vitro. 6-Azauridine 5'-monophosphate (6-AzaUMP) stimulated synthetase II, possibly in an allosteric manner. However, in view of the potency as an activator and the tissue levels, 6-azaUMP may be only partially responsible for the stimulation. Adenine nucleotide levels in the tissue showed only minor changes after brief exposure (15 min) to 6-azauridine. The level of UTP and UDP, potent inhibitors for synthetase II, showed no significant change. The level of 5-phosphoribosyl 1-pyrophosphate (PPRibP), a potent positive effector for the synthetase II, showed a more than 1.5-fold increase after 15 min. The relative importance of these factors was evaluated by assay of the synthetase, partially purified from mouse spleen, under simulated conditions in vitro. The results indicated that the enhanced level of PPRibP played a major role in increasing the production of carbamoyl phosphate. In Ehrlich ascites cells in vitro, where 6-azauridine did not increase carbamoyl phosphate production, the basal PPRibP level was high (range over 0.1 mM) and the changes in the level, brought about by the analogue, were relatively small.

Animals↗
PubMed1982

Transport of carbamyl phosphate synthetase I and ornithine transcarbamylase into mitochondria. Inhibition by rhodamine 123 and accumulation of enzyme precursors in isolated hepatocytes.

Carbamoyl-phosphate synthetase (ammonia) (EC 6.3.4.16) and ornithine carbamoyltransferase (EC 2.1.3.3) are matrix enzymes synthesized outside the mitochondria in the form of larger precursors and are transported rapidly into mitochondria, in association with post-translational proteolytic processing to the mature enzymes. Treatment of isolated rat hepatocytes with 40 micrograms/ml of rhodamine 123, a laser dye which specifically stains mitochondria, resulted both in a strong inhibition of the processing of the enzyme precursors and in accumulation. Rhodamine 123 did not specifically inhibit the synthesis of the synthetase and the transcarbamylase precursors in a reticulocyte lysate cell-free system programmed with rat liver free polysomes. The dye strongly inhibited the uptake and processing of the ornithine transcarbamylase precursor by isolated rat liver mitochondria. When the mitochondria and the medium were separated by centrifugation, the unprocessed precursor was recovered almost exclusively in the medium. These results indicate that rhodamine 123 inhibits either the binding of the enzyme precursors to the mitochondria or their transport into the organelle.

Animals↗
PubMed1982

An extracellular polysaccharide produced by Zoogloea ramigera 115.

A weakly acidic polysaccharide was purified from the extracellular zoogloeal matrix produced by Zoogloeal ramigera 115. The purified polysaccharide was homogeneous as judged by sedimentation analysis, and the average molecular weight was estimated to be about 10(5) by gel permeation chromatography of the fully methylated preparation. The polysaccharide was composed of D-glucose, D-galactose and pyruvic acid in an approximate molar ratio 11:3:1.5. On the basis of methylation, periodate oxidation, Smith degradation and partial hydrolysis, the following highly branched structure was deduced for the polysaccharide: a long chain mainly consisting of beta 1 leads to 4-linked glucose residues branching at the C-3 or C-6 position of galactose residues which are present in beta 1 leads to 4 or beta 1 leads to 3 linkages as the minor component of the long chain; pyruvic acid residues, the sole acidic component, are linked to the nonreducing end and/or 1,3-linked glucose residues through 4,6-ketal linkages. The purified polysaccharide was not readily soluble in water and had a high affinity for several metallic ions (e.g, 0.25 mumol Fe3+/mg, and 0.17 mumol Fe2+ mg). Upon addition of metallic ions (1 mM) to a gelatinous aqueous solution of the polysaccharide (K+ form, 0.125%), more than 80% of it immediately coprecipitated out with them.

Chemical Phenomena↗
PubMed1982

Effects of a new angiotensin-converting enzyme inhibitor, MK 421, in normal men and patients.

Effects of MK 421, a new angiotensin-converting enzyme inhibitor, were studied in normal men and patients. MK 421 was given at 0900 h as a single oral dose of 20 mg, to 5 normal men and 2 patients with essential hypertension and 10 mg to a patient with Bartter's syndrome, in the recumbent position. In all of them blood pressure (BP) fell, plasma angiotensin I (Pl AI) and plasma renin activity (PRA) increased, and plasma aldosterone (PA) decreased from 2 h to 6 h. Maximum effects were observed at 4 or 6 h. Then the effects attenuated gradually but still remained at 24 h. In the same 5 normal men angiotensin I (AI) was infused iv at a rate of 20 ng/kg . min from 0900 h to 1500 h, from 2030 h to 2100 h, and the next morning from 0830 to 0900 h. At first the BP rose and PA increased. The onset of the BP fall was at 35, 55, 60, 70 and 85 min in each subject, respectively. Then the BP and PA began to decrease and the Pl AI and PRA began to increase. The maximum effects were observed at 4 or 6 h. Then these inhibitory effects on the AI were attenuated but still remained at 24 h. The 2 patients with essential hypertension and a patient with malignant hypertension was treated with MK 421 at a daily doses of 5 to 40 mg for 2 to 6 months. They all showed a fall in BP and no side-effects were noted. From these results it is concluded that MK 421 is a strong and long-acting antihypertensive drug and its clinical application seems very useful for the treatment of hypertension.

Adult↗
PubMed1982

Biological activity of des-asp1-des-arg2-angiotensin II in man.

The biological activity of des-asp1-des-arg2-angiotensin II (3-8AII) was studied in man. When 3-8AII was infused iv at rates of 22 and 308 pmol (17.5 and 250 ng)/kg . min separately into 5 normal men each for 120 min, blood pressure showed no change, plasma renin activity (PRA) decreased gradually and plasma aldosterone showed a gradual slight increase. The lower dose of 3-8AII partially inhibited captopril-induced PRA increase and plasma aldosterone decrease in the same 5 normal men and the higher dose of the hexapeptide completely abolished them. In one of the 5 normal men blood pressure rose in response to doses of 3-8AII greater than 2220 pmol (1750 ng)/kg . min. When 3-8AII was infused iv at 308 pmol/kg . min into 2 patients with Bartter's syndrome for 60 min, it caused marked decrease in PRA and plasma aldosterone but no change in blood pressure. This decrease in plasma aldosterone is thought to be secondary to the decrease in PRA. From these results it is evident that 3-8AII has a minimal pressor action, a weak aldosterone-stimulating action and a significant renin-suppressing action in man and this PRA-lowering action is thought to be due to direct inhibition of renin release by its whole molecule or a smaller part of the molecule.

Adult↗
PubMed1981

Synthesis, intracellular transport, and processing of the precursors for mitochondrial ornithine transcarbamylase and carbamoyl-phosphate synthetase I in isolated hepatocytes.

The synthesis and intracellular transport of the mitochondrial matrix enzymes ornithine transcarbamylase (carbamoylphosphate: L-ornithine carbamoyltransferase, EC 2.1.3.3.) and carbamoyl-phosphate synthetase (ammonia) I [carbon-dioxide:ammonia ligase (ADP-forming, carbamate-phosphorylating), EC 6.3.4.16] were studied in isolated rat hepatocytes. In pulse experiments at 37 degrees C, the larger precursors of the two enzymes appeared in the cytosol of the liver cells, where radioactivity levels of the precursors reached a plateau in 10-20 min after the pulse. The pulse-labeled mature enzymes appeared in the particulate fraction (containing mitochondria) after a time lag and increased almost linearly with time up to 40 min. The specific radioactivities of the precursors in the cytosol were much higher than those of the mature enzymes in the particulate fraction. In pulse--chase experiments, the labeled precursors disappeared from the cytosol with estimated half-lives of about 1-2 min. These results indicate that ornithine transcarbamylase and carbamoyl-phosphate synthetase I are initially synthesized as larger precursors and exist in a cytosolic pool from which they are transported into mitochondria and processed there to the mature enzymes concomitantly with or immediately after transport. Although the rates of synthesis, transport, and processing were decreased about 3-fold at 25 degrees C (as compared to incubation at 37 degrees C), the pool size of the precursors in the cytosol were somewhat larger at this temperature.

Animals↗
PubMed1981

Suppression of captopril-induced increase in plasma renin activity by des-Asp1-,Ileu8-angiotensin II in man.

One hundred milligrams of oral captopril (SQ 14225) caused a significant increase in PRA and a significant decrease in plasma aldosterone (PA) in five normal men and five hypertensive patients. Blood pressure (BP) showed no change in the normal men, but it fell significantly in the patients. An iv infusion of 200 ng/kg.min des-Asp1-,Ileu8-angiotensin II (AIIIA) for 2 h caused a significant decrease in PRA and a slight but significant increase in PA, but caused no change in BP in the normal men. When 100 mg captopril were given orally immediately before the start of the AIIIA infusion, BP showed no change in the normal men, but fell in the patients. However, PRA showed a significant decrease and PA showed a slight but significant increase in both the normal men and the patients, except for one patient with renovascular hypertension who showed a decrease in PA. Thus, this suppression of captopril-induced PRA increase by AIIIA, a derivative of angiotensin II, is not related to BP change, and it suggests that the principal cause of the PRA increase after captopril is a disappearance of endogenous angiotensin II.

Adult↗
PubMed1981

Normotensive primary aldosteronism: report of a case.

A 23-yr-old male patient with normotensive primary aldosteronism is reported. He complained of muscle weakness, polydipsia, and polyuria. His blood pressure was generally 118/60 to 124/70 mm Hg. Serum sodium, potassium and chloride were 152.2.2, and 108 meq/liter, respectively. Arterial blood pH, glomerular filtration rate, renal plasma flow and circulating plasma and blood volumes were normal, and plasma bicarbonate was normal or elevated. PRA was 0.16 ng/ml.h and did not increase significantly after sodium deprivation, ambulation, and iv furosemide injection. Plasma aldosterone was 64.1 ng/100 ml. He showed pressor responses to infused angiotensin II and norepinephrine which were similar to those in normal men. Adrenal scintiscanning after iv injection of [131I]6 beta-iodomethyl-19-nor-cholesterol during dexamethasone administration showed dense uptake on the right adrenal and minimal uptake on the left. Intravenous infusion of angiotensin III at a rate of 20 ng/kg. min for 30 min did not cause an increase in plasma aldosterone. Serum electrolytes became normal after spironolactone but not after dexamethasone. At surgery, the right adrenal, bearing a benign adenoma, was removed. After surgery, blood pressure was unchanged, but all biochemical abnormalities disappeared. The cause of this normotension remains to be elucidated, but the diagnosis criteria of primary aldosteronism should now be partly modified.

Adenoma↗
PubMed1980

Anticoagulant activity of artificial biomedical materials with co-immobilized antithrombin III and heparin.

An approach to providing anticoagulant activity to biomedical materials was presented, applying an immobilization technique. Antithrombin III (AT III) inactivates the activated coagulation factors including Factor Xa and thrombin. Heparin stimulates the inactivation of Factor Xa and thrombin by AT III. Thus AT III and heparin were co-immobilized on Sepharose 4B, polyvinyl alcohol, polyhydroxy-ethyl methacrylate and silicone-coated nylon by the cyanogen bromide procedure. Those co-immobilized preparations, abbreviated as I-AT III . Hep, actively neutralized both Factor Xa and thrombin. The activity of I-AT III . Hep was much higher than immobilized heparin and/or immobilized AT III. I-AT III . Hep, like soluble AT III and heparin, instantaneously neutralized both thrombin and Factor Xa. When two enzymes, thrombin and Factor Xa, were present, I-AT III . Hep neutralized Factor Xa in preference to thrombin : The neutralization of thrombin was inhibited by the presence of Factor Xa, but neutralization of Factor Xa was independent of the presence of thrombin. The amount of Factor Xa neutralized was higher than that of thrombin.

Animals↗
PubMed1980

Biological activity of des-Asp1-angiotensin I in man.

The biological activity of des-Asp1-angiotensin I (des-Asp1-AI) was studied in five normal men. An iv infusion of 300 ng (258 pmol)/kg.min des-Asp1-AI caused a remarkable rise in blood pressure, a decrease in PRA, and an increase in plasma aldosterone concentration. The pressor and steroidogenic actions of this dose of des-Asp1-AI were slightly less than those of 100 ng (111 pmol)/kg.min des-Asp1-angiotensin II [Angotensin III (AIII)] which we reported previously and were abolished by a single oral administration of 100 mg of a converting enzyme inhibitor, SQ 14225. These results indicate that in man, as in animals, a rise in blood pressure and an increase in plasma aldosterone concentration after an infusion of des-Asp1-AI are entirely due to the actions of AIII converted from this nonapeptide, and that the conversion rate of des-Asp1-AI to AIII in normal men is less than 43%. This is much less than the conversion rate of angiotensin I to angiotensin II. It seems unlikely that des-Asp1-AI has physiological significance in the human renin-angiotensin-aldosterone system.

Aldosterone↗
PubMed1980

Effects of diltiazem hydrochloride on pressor and steroidogenic actions of angiotensins and norepinephrine in man.

The effect of diltiazem hydrochloride (DTZ), a calcium-antagonist, on pressor and steroidogenic action of angiotensin II (AII), angiotensin III (AIII) and norepinephrine (NE) was studied in 5 normal men. AII, AIII and NE were infused intravenously for 50 min from 0900 hr at a rate of 20 ng/kg/min, 100 ng/kg/min and 200 ng/kg/min, respectively. DTZ was infused intravenously alone or in combination with each of these pressor substances at a rate of 1 mg/min from 0910 hr to 0930 hr. DTZ alone did not cause significant changes in blood pressure (BP) and plasma aldosterone concentration (P1 Aldo). On the other hand, DTZ combined with AII, AIII or NE significantly inhibited the rise in BP induced by these pressor substances. DTZ also inhibited the NE-induced increase in P1 Aldo, whereas it did dot alter AII-, or AIII-induced increase in P1 Aldo. These results indicate that in normal men pressor actions of AII, AIII and NE are calcium-dependent and calcium ions are also involved in NE-induced increase in P1 Aldo.

Adult↗