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Biomedical subjects

K Ichihara

Publications and source records attributed to K Ichihara.

At least 307 records · Page 17Linked to original sources

[Effects of labetalol on the circulatory system (author's transl)].

Effects of labetalol on the cardiovascular system were studied in dogs, guinea pigs, rats, rabbits, and bullfrogs. In dogs anesthetized with pentobarbital, labetalol decreased heart rate, arterial blood pressure, and myocardial contractile force, and inhibited carotid sinus reflex, without affecting pO2 and pH of circulating blood, urine volume, and urinary excretion of sodium and potassium. Alpha- and beta-adrenergic blocking action of labetalol was demonstrated in dog hearts, arterial preparations of guinea pigs and rats, isolated rabbit hearts, and bullfrog hind limb and rabbit ear preparations. In bullfrog hind limb and rabbit ear preparations, labetalol dilated blood vessels in concentrations larger than those which produced alpha- and beta-adrenergic blockade. The dilatation of blood vessels was observed only when labetalol was added to the perfusate, whereas alpha- and beta-adrenergic blockade continued even after removal of labetalol from the perfusate. It is concluded that labetalol blocks alpha- and beta-adrenergic receptors in the heart and blood vessels of the species used herein, and that this compound inhibits carotid sinus reflex in dogs. In addition, the dilatation of the blood vessels of the bullfrog hind limb and rabbit ear as evoked by labetalol probably involves a mechanism different from that of adrenergic blockade.

Adrenergic alpha-Antagonists↗

Effect of niludipine on ischemic myocardial metabolism in the dog.

The effect of pretreatment with 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine carbonic acid-bis(2-propoxyethyl) ester (niludipine, Bay a 7168) (10 microgram/kg i.v.) on myocardial metabolic response to coronary artery ligation was studied in dogs anesthetized with pentobarbital. The results are summarized as follows: 1. Bay a 7168 lowered systolic and diastolic blood pressures markedly, and decreased heart rate slightly. 2. Bay a 7168 increased the endo- and epicardial phosphorylase activity significantly. 3. Bay a 7168 increased the endo- and epicardial ATP levels significantly. 4. Coronary artery ligation increased the endo- and epicardial activity of phosphorylase and decreased the endo- and epicardial glycogen levels. 5. In the presence of Bay a 7168, acceleration of glycogenolysis being caused by coronary artery ligation, was not detected. 6. Changes in the levels of myocardial carbohydrate intermediates being caused by coronary artery ligation, were not modified by pretreatment with Bay a 7168.

Adenosine Triphosphate↗

Kinetic aspects of the antigen-antibody reaction in various radioimmunoassays: effect of delayed addition of labeled or unlabeled antigens on sensitivity of assay.

The kinetics of the antigen-antibody reaction were examined systematically in four kinds of double-antibody radioimmunoassay (RIA). In all the RIAs, the dose-response curves obtained on delayed addition by 24 to 48 h of labeled antigens (curves B), were shifted downwards and to the left of those obtained on simultaneous addition of the reagents (curves A), resulting in improved sensitivity of the assay. On the contrary, the dose-response curves obtained on delayed addition of unlabeled antigens (curves C), were shifted upwards and to the right of curves A, resulting in reduced sensitivity. In human thyrotropin (hTSH) RIA, curves B and C approached curves A very little, even after 168 h of incubation. A similar phenomenon was observed with anti-hTSH antisera from five different sources at two incubation temperatures, and the dilution curves of 125I-labeled hTSH and unlabeled hTSH appeared to be parallel. Therefore, the phenomenon observed with hTSH RIA could not be attributed to the assay conditions or to peculiar properties of the reagents used. In insulin RIA, the reversibilities of the shifts of curves B and C were slight but comparable to those observed in hTSH RIA. In 1-3,5,3'-triiodothyronine RIA, curves B and C gradually approached curves A on prolonged incubation and curves B became nearly identical with curves A after 98 h of incubation. On the other hand, in alpha-fetoprotein (AFP) RIA, curves B and C did not approach curves A, even on prolonged incubation for up to 288 h. The "equilibrium affinity constants" of the antibodies were of the same order of magnitude, thus it is unlikely that differences in the constants can account for the differences in the reversibility of these RIAs. In APF RIA, a significant amount of the antigen-antibody complex was precipitated without second antibody after centrifugation at 3000 X g. These findings suggest that the extent of dissociation of the immune complexes depends on their size, which in turn is related to the molecular weight of the antigen.

Antigen-Antibody Reactions↗

Synthesis of adenosine 3',5'-monophosphate by guanylate cyclase, a new pathway for its formation.

The 105 000 X g gupernatant fractions from homogenates of various rat tissues catalyzed the formation of both cyclic GMP and cyclic AMP from GTP and ATP, respectively. Generally cyclic AMP formation with crude or purified preparations of soluble guanylate cyclase was only observed when enzyme activity was increased with sodium azide, sodium nitroprusside, N-methyl-N'-nitro-N-nitrosoguanidine, sodium nitrite, nitric oxide gas, hydroxyl radical and sodium arachidonate. Sodium fluoride did not alter the formation of either cyclic nucleotide. After chromatography of supernatant preparations on Sephadex G-200 columns or polyacrylamide gel electrophoresis, the formation of cyclic AMP and cyclic GMP was catalyzed by similar fractions. These studies indicate that the properties of guanylate cyclase are altered with activation. Since the synthesis of cyclic AMP and cyclic GMP reported in this study appears to be catalyzed by the same protein, one of the properties of activated guanylate cyclase is its ability to catalyze the formation of cyclic AMP from ATP. The properties of this newly described pathway for cyclic AMP formation are quite different from those previously described for adenylate cyclase preparations. The physiological significance of this pathway for cyclic AMP formation is not known. However, these studies suggest that the effects of some agents and processes to increase cyclic AMP accumulation in tissue could result from the activation of either adenylate cyclase or guanylate cyclase.

Animals↗

Seasonality of birth in sporadic cretinism.

The seasonal distribution of birth dates of 31 patients with sporadic cretinism due to thyroid dysgenesis was analyzed in Osaka area for 14 years. The incidence was statistically high in the summer months. A hypothesis that some environmental factors such as viral infection may cause the disease is proposed.

Birth Rate↗

Longitudinal study or serum thyroid hormones, chorionic gonadotrophin and thyrotrophin during and after normal pregnancy.

Measurements of serum levels of thyroxine (T4), free T4, 3,5,3'-triiodothyronine (T3), free T3, 3,3',5'-triiodothyronine (reverse T3, rT3), thyroxine-binding globulin capacity (TBGcap), chorionic gonadotrophin (hCG) and thyrotrophin (TSH) were carried out prospectively in eight women with uncomplicated pregnancies, in order to examine interrelationships between the thyroid gland and thyroid stimulating hormones during pregnancy. During pregnancy the levels of T4, free T4, T3, rT3 and TBGcap were significantly elevated, and TSH was decreased. It was noted that the elevation of T4 was maintained from the 8th to the 27th week of gestation while the level of TBGcap progressively increased. The levels of free T4 and rT3 in the first and third trimesters were significantly higher than those of age-matched, non-pregnant women. The levels of hCG showed a biphasic variation, with a peak in the 8th to 15th weeks, followed by a decline in the second trimester and a small, secondary elevation in the 32nd to 39th weeks. This later elevation was positively correlated with changes in free T4 and free T3 levels. The increase of serum T4 accompanied by an increase of free T4 in the first trimester appeared due to augmented secretion of T4, rather than being secondary to the elevated levels of TBGcap.

Adolescent↗

Fatty acid omega and (omega-1)-Hydroxylation in rabbit intestinal mucosa microsomes.

The microsomes from rabbit intestinal mucosa which had been washed quickly and thoroughly with phenylmethylsulfonyl fluoride were found to catalyze the hydroxylation of fatty acids in the presence of NADPH and molecular oxygen. Myristic and palmitic acids were converted to the corresponding omega-and (omega-1)-hydroxy fatty acids, whereas lauric acid was converted only to 12-hydroxylauric acid, and capric acid, to 9-and 10-hydroxycapric acids together with an unknown polar acid. Among these fatty acids, both myristic and lauric acids appeared to be the most efficient substrates. The inhibition of the hydroxylation by SKF 525-A and carbon monoxide suggested that the activity depended upon cytochrome P-450. The specific activity of the fatty acid hydroxylation was almost constant along the small intestine, while the aminopyrine N-demethylation activity and the cytochrome P-450 content were highest at the proximal end of the intestine and progressively declined toward the caudal end. The cytochrome P-450 was solubilized from the intestinal microsomes and purified by 6-amino-n-hexyl Sepharose 4B chromatography. The partially purified cytochrome P-450 was active in fatty acid hydroxylation in combination with intestinal NADPH-cytochrome c reductase and phosphatidylcholine.

Animals↗

Effect of verapamil and nifedipine on ischemic myocardial metabolism in dogs.

The effect of pretreatment with verapamil (100 micrograms/kg i.v.) or nifedipine (10 micrograms/kg i.v.) on ischemic myocardial metabolism was studied in dogs anesthetized with pentobarbital. The results are summarized as follows: 1. Verapamil or nifedipine lowered both systolic and diastolic blood pressures markedly, and increased heart rate slightly. 2. Verapamil or nifedipine increased both endo- and epicardial phosphorylase activities significantly. 3. Coronary artery ligation increased the phosphorylase activity, and also increased the levels of glucose-6-phosphate, fructose-6-phosphate, and lactate, and decreased the levels of glycogen, fructose-1,6-diphosphate, and phosphocreatine in both endo- and epicardial layers, without affecting the level of the endo- and epicardial adenosine triphosphate. 4. In the presence of verapamil or nifedipine, coronary artery ligation did not increase but decreased the phosphorylase activity that had been increased by verapamil or nifedipine alone. 5. Changes in the levels of intermediates induced by coronary artery ligation were not markedly influenced by pretreatment of the dog with verapamil or nifedipine.

Animals↗

Effect of ouabain on myocardial metabolic and contractile responses to coronary ligation.

The effect of pretreatment with ouabain (40 microgram/kg, i.v.) on myocardial metabolic and contractile responses to regional ischemia induced by coronary artery ligation was studied in the canine left ventricle. In control dogs, ischemia increased activity of phosphorylase a and the levels of glucose-6-phosphate and lactate, and decreased the levels of glycogen and phosphocreatine, without affecting the levels of adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate (AMP). Ouabain increased the activity of phosphorylase a. In ouabain-treated dogs, ischemia did not further increase the phosphorylase a activity but it increased the epicardial AMP level. Other metabolic responses to ischemia in ouabain-treated dogs were similar to those in control dogs. In control dogs, myocardial contractile force decreased by about 10% after ischemia, but blood pressure and heart rate remained unchanged. Ouabain increased contractile force by about 32%. In ouabain-treated dogs, ischemia decreased contractile force by about 54% without affecting blood pressure and heart rate. It is concluded that ouabain increases the activity of the myocardial phosphorylase a and that the inotropic action of ouabain can be nullified by coronary artery ligation.

Animals↗

A new method of paired thyrotropin assay as a screening test for neonatal hypothyroidism.

A simple and reliable method of paired TSH assay was developed and used in screening for neonatal primary hypothyroidism. In this method, a paired assay is first done. Equal parts of the extracts of dried blood spots on filter paper (9 mm diameter) from two infants 4-7 days old are combined and assayed for TSH by double antibody RIA. If the value obtained is over the cut-off point, the extracts are assayed separately for TSH in a second assay to identify the abnormal sample. Two systems, A and B, with different cut-off points were tested. On the basis of reference blood samples (serum levels of TSH, 80 microU/ml in system A and 40 microU/ml in system B), the cut-off point was selected as follows: upper 5 (A) or 4 (B) percentile in the paired assay and values of reference blood samples in the second individual assay. Four cases (2 in A and 2 in B) of neonatal primary hypothyroidism were found among 25 infants (23 in A and 2 in B) who were recalled from a general population 41,400 infants (24,200 in A and 17,200 in B) by 22,700 assays. This paired TSH neonatal hypothyroidism.

Congenital Hypothyroidism↗

Changes of serum immunoglobulins IgG, IgA, IgM, and IgE during pregnancy.

The serum levels of immunoglobulins at various times throughout pregnancy were measured in 11 healthy women. The concentrations of IgG, IgA, and IgM decreased significantly in the second and third trimesters, the mean decreases at the second trimester being 18, 13, and 9%, respectively. When the decreases were expressed on the basis of serum total protein, the decreases in IgG and IgA were significant but the decrease in IgM was not. The level of IgE either decreased or increased during pregnancy. Maternal age, emesis, ABO-incompatibility, and the sex and weight of the baby at birth were not related to the initial concentration or to the extent of decrease of immunoglobulins during pregnancy. In a case of Rh incompatibility, increase of immunoglobulins was observed concomitantly with the transient appearance of anti-Rh(D) antibody. Immunoglobulin depletion in pregnancy seems to result from both immune suppression and hemodilution.

Adult↗