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Biomedical subjects

K Ichihara

Publications and source records attributed to K Ichihara.

At least 289 records · Page 16Linked to original sources

Effect of diltiazem, a calcium antagonist, on myocardial pH in ischemic canine heart.

The effect of diltiazem on ischemic myocardial acidosis was studied in the canine heart whose left anterior descending coronary artery was partially occluded to reduce coronary flow to about one-third (partial occlusion). Myocardial pH was measured by use of a micro glass pH electrode. The pH decreased from 7.53 to 6.93 by partial occlusion and appeared to reach a steady state within 30 min. Saline or drugs were injected i.v. 30 min after partial occlusion. The decreased pH increased spontaneously by 34% of the total reduction of pH in the next 60 min after saline injection. Diltiazem (100 micrograms/kg) potentiated the increase in pH; the pH increased by 76% 60 min after the injection. Propranolol (1 mg/kg) also potentiated the increase in pH that had been decreased by partial occlusion. The relation between pH decrease and the tissue levels of metabolites was also studied. The reduction of myocardial pH from 7.5 to 6.8 was accompanied by a 2-fold increase in the tissue lactate content and by decreases in the ATP and creatine phosphate contents. There was a significant correlation between the hydrogen ion concentration calculated from the pH and each of the lactate, ATP and creatine phosphate contents. The present study indicates that diltiazem attenuates ischemic myocardial acidosis.

Adenosine Triphosphate↗

Radioimmunoassay of "free thyroxin" in dried blood spots on filter paper - preliminary observations on the effective differentiation of subjects with congenital hypothyroidism from those with subnormal thyroxin-binding globulin and normal subjects.

In this sensitive, simple method for measuring "free thyroxin" (FT4) in eluates of dried blood spots on filter paper by use of a radioimmunoassay kit (Amerlex Free T4 RIA), the measurable range of FT4 is 1.8 to 57 ng/L (equivalent to the concentration in serum), or 7 to 237 fg/tube. The mean coefficients of variation for within assay-within spots, within assay-between spots, and between assays were 5.3%, 5.0%, and 6.2%, respectively. FT4 in blood spotted on filter paper is stable for at least a month when dried and kept at either -20 degrees C, 4 degrees C, room temperature (about 25 degrees C), or 37 degrees C. The results for FT4 in dried blood spots correlated closely with the free-T4 concentration in serum (r = 0.99). The method can be used to differentiate cases of primary and secondary hypothyroidism from normal subjects and those with subnormal thyroxin-binding globulin. This method may be useful in screening for congenital hypothyroidism, because sample-retesting is not necessary.

Adolescent↗

Some properties of a hexadecane hydroxylation system in rabbit intestinal mucosa microsomes.

Among many different tissues of rabbit, hexadecane hydroxylation activity was found in only small intestine and liver microsomes. Both activities for hexadecane and decane hydroxylation in intestinal microsomes were significantly higher than those in liver microsomes. In contrast, the hydroxylation activities of p-xylene, benzo(a)pyrene, and decanol, and the demethylation activity of aminopyrine in the former were much lower than those in the latter. The intestinal microsomes converted [1-14C]hexadecane to cetyl alcohol, but not further to palmitic acid. Hexadecane hydroxylation activity was found to be markedly stimulated by non-ionic detergents such as Triton X-100, Nonident P-40, and Emulgen 913. Phosphatidylcholine and phosphatidylethanolamine stimulated the activity to a lesser extent. The hydroxylation was inhibited by various aliphatic hydrocarbons with carbon numbers larger than 10, but not by aromatic and polycyclic hydrocarbons. Hexadecane hydroxylation activity was solubilized from the intestinal microsomes and reconstituted with a partially purified cytochrome P-450 fraction, and intestinal NADPH-cytochrome c reductase, or spinach ferredoxin and ferredoxin-NADP reductase. The chromatography of the crude cytochrome P-450 preparation on hydroxylapatite separated at least two cytochrome P-450 fractions; one preferentially hydroxylating hexadecane, and the other preferentially hydroxylating myristic acid. The results suggest that rabbit intestinal mucosa microsomes had a cytochrome P-450 species specialized for hexadecane hydroxylation.

Alkanes↗

Effect of cytochrome b5 on fatty acid omega- and (omega-1)-hydroxylation catalyzed by partially purified cytochrome P-450 from rabbit kidney cortex microsomes.

Cytochrome P-450 was solubilized from kidney cortex microsomes of rabbits treated with 3-methylcholanthrene and partially purified by chromatography on 6-amino-n-hexyl Sepharose 4B and heparin-Sepharose CL-6B columns. Fatty acid omega- and (omega-1)-hydroxylation activity was reconstituted from the partially purified cytochrome P-450 and NADPH-cytochrome c reductase, with phosphatidylethanolamine or phosphatidylcholine. The activity was further stimulated by addition of detergent-solubilized cytochrome b5 from rabbit liver microsomes. Trypsin-solubilized or boiled detergent-solubilized cytochrome b5 had no effect. Among fatty acids tested, caprate, laurate, myristate, and palmitate were the most effective substrates. When caprate and laurate were used as the substrates, the products were the corresponding omega- and (omega-1)-hydroxy fatty acids. The ratio of these products was altered by addition of cytochrome b5. On the other hand, when myristate and palmitate were the substrates, small amounts of unknown polar fatty acids were also formed besides omega- and (omega-1)-hydroxy fatty acids, and the ratio of these products was not affected by addition of cytochrome b5. Benzo(a)pyrene hydroxylation activity was also reconstituted from the same cytochrome P-450 preparation, NADPH-cytochrome c reductase, and phosphatidylserine. However, cytochrome b5 showed only a slight stimulation. The possibility that different cytochrome P-450 species are involved in fatty acid and benzo(a)pyrene hydroxylations is discussed.

Animals↗

Elevated levels of circulating carcinoembryonic antigen in hypothyroidism.

The level of circulating carcinoembryonic antigen (CEA) was measured in 148 patients with various thyroid diseases. A significantly high frequency of positive CEA was observed in hypothyroid patients with Hashimoto's disease, but the serum CEA levels were not correlated with the serum calcitonin concentrations in Hashimoto's disease. The CEA levels were inversely correlated with the serum T4 concentrations (P less than 0.001) and were positively correlated with the serum TSH concentrations (P less than 0.001), but not with the titers of serum antithyroid antibodies or the size of goiter in autoimmune thyroid disease. Moreover, the increase in CEA was significantly related to the duration of hypothyroidism (P less than 0.001). The high CEA levels in all hypothyroid patients decreased when the patients attained a euthyroid state after thyroid hormone therapy for 4-9 months. The gradual decrease in the serum CEA levels during treatment was roughly correlated with the decreases in serum cholesterol concentration and serum lactic dehydrogenase and glutamic oxalacetic transaminase activities. On Sephadex G-200 column chromatography of serum from hypothyroid patients, the CEA immunoreactivity, like purified standard CEA, was recovered in the large molecular weight fraction. These findings indicate that elevated CEA levels in hypothyroid patients do not necessarily indicate malignancy. CEA elevation in hypothyroidism may be caused by decreased degradation of CEA.

Adolescent↗

Electron microscope study of vertebrate liver innervation.

Liver fine structure was studied in various groups of vertebrates to reveal intrahepatic nerves. Nerve fibers were found in the connective tissue of the liver in all mammals, birds, and reptiles studied (Japanese monkey, crab-eating monkey, rabbit, guinea pig, rat, golden hamster, pigeon, Japanese quail, and turtle, Pseudemys scripta). Nerve fibers also made direct contact with hepatocytes in these animals except for the rat and the golden hamster. Intrahepatic nerves were rare or absent in amphibians (Rana catesbeiana and Cynops pyrrhogaster pyrrhogaster) and fishes (Anguilla japonica and Misgurnus anguillicaudatus). The livers of mammals and birds consisted of hepatic lobules and interlobular connective tissue carrying a portal triad. The liver of lower vertebrates was a simple mass of hepatic cell cords and contained relatively small amounts of connective tissue. The increased number of intrahepatic nerves appears to be correlated with the development of higher organization of liver structure and a concomitant increase in the amount of connective tissue.

Animals↗

Reconstruction of aryl hydrocarbon hydroxylase from rabbit intestinal mucosa microsomes.

Benzo(a)pyene hydroxylation activity was solubilized from rabbit intestinal mucosa microsomes and reconstituted with a cytochrome P-450 preparation obtained by fractionation with 6-amino-n-hexyl Sepharose 4B, hydroxylapatite and CM-Sephadex C-50, and partially purified NADPH-cytochrome c reductase. Phosphatidylserine was required for the maximal activity, while phosphatidylcholine had no stimulatory effect. The carbon monoxide difference spectrum of the cytochrome P-450 fraction showed a maximum peak at 450 nm. Although another cytochrome P-450 fraction was active for hexadecane hydroxylation, this fraction had little activity. The results indicate that more than one cytochrome P-450 exists in the intestinal mucosa microsomes.

Animals↗

Utilization of leucine by working rat heart.

Leucine provided substrate to partially support mechanical activity of working rat hearts; the beneficial effect on peak systolic pressure development was more marked as leucine concentration was increased to 10 mM. In Langendorff preparations that had been exposed to 5 mM [U-14C]leucine, the imposition of cardiac work was accompanied by a threefold increase in the rate of 14CO2 production within the first 30 s; however, the rate decreased 40% in the next 10 min. This transient acceleration of 14CO2 production was not observed when [1-14C]leucine was provided and appeared to be due to oxidation of a tissue pool of radioactive intermediates that was present after 10 min of Langendorff perfusion. Over a period of 1 h, oxidation of either [U-14C]- or [1-14C]leucine increased 25-40% in working compared to Langendorff preparations that were supplied 5 mM leucine and 11 mM glucose. In working hearts that were supplied a substrate and hormone mixture that simulated normal plasma and 1 mM leucine, a concentration found in the plasma of diabetic but not normal rats, leucine oxidation was accelerated 73% by work but amounted to only 3.3% of oxygen consumption.

Animals↗

Fluctuation of the plasma TRH level in normal subjects in a 4-hour observation period.

Radioimmunoassayable TRH and TSH were measured in plasma samples taken at 5 min intervals for 4 hr (2100-0200 hr) from 4 normal male subjects. Three subjects showed a TSH surge at 2135 hr, 2455 hr and 0150 hr, respectively. The mean plasma TRH level of the 4 subjects was 10.3-11.7 pg/ml. Plasma TRH showed random fluctuation, which did not coincide with the nocturnal increase in plasma TSH.

Adult↗