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Biomedical subjects

Y Kosaka

Publications and source records attributed to Y Kosaka.

At least 163 records · Page 9Linked to original sources
PubMed1989

Evaluation of des-gamma-carboxy prothrombin as a marker protein of hepatocellular carcinoma.

We measured des-gamma-carboxyglutamic acid prothrombin (protein induced by vitamin K absence or antagonist-Factor II: [PIVKA-II]) in plasmas of normal subjects, patients with thrombotic disease, those with hepatic disease including hepatocellular carcinoma, and those with carcinoma of other tissues, and compared the results with results of blood coagulation tests used for the examination of hepatic function. In addition, in the patients with hepatic disease, PIVKA-II and alpha-fetoprotein (AFP) levels were compared. The PIVKA-II level was frequently high in patients with thrombotic disease given warfarin therapy and those with hepatocellular carcinoma. However, in patients with thrombotic disease who were not given warfarin therapy, no significant correlation was seen between the PIVKA-II value and the results of the thrombotest or hepaplastin test, suggesting no association between the PIVKA-II level and the degree of impairment of hepatic function. In 70 patients with hepatocellular carcinoma, the percentage of patients positive for PIVKA-II (greater than or equal to 0.1 micrograms/ml) and those positive for AFP (greater than or equal to 20 ng/ml) were similar (77% and 74%, respectively). Pearson's correlation of coefficient between the PIVKA-II value and the AFP value in the 70 patients was 0.463. However, false-positive rates in patients with hepatic disease other than hepatocellular carcinoma were lower for PIVKA-II. Combined assessment of PIVKA-II and AFP increased positive rates and allowed exclusion of false-positive patients. The plasma PIVKA-II level is suggested to be useful as an indicator of warfarin control in patients with thrombotic disease, as a marker of hepatocellular carcinoma, and is particularly of value when assessed in combination with AFP.

Biomarkers↗
PubMed1989

A domain composed of epidermal growth factor-like structures of human thrombomodulin is essential for thrombin binding and for protein C activation.

Thrombomodulin, an endothelial thrombin receptor, acts as a cofactor for the thrombin-catalyzed activation of anticoagulant protein C. The extracellular region of human thrombomodulin consists of three tentative domains, a NH2-terminal domain (D1), a domain involving six consecutive epidermal growth factor-like structures (D2), and an O-glycosylation-rich domain (D3). To identify the domain onto which thrombin binds, a series of recombinant proteins corresponding to the entire protein, D1, D2, D1 + D2, D1 + D2 + D3, and D2 + D3 were expressed in simian COS-1 cells. The proteins were partially purified by rabbit anti-thrombomodulin-F(ab')2-agarose chromatography. Western blotting analysis showed the expression of the respective recombinant proteins. All proteins involving D2, as well as D2 alone, had cofactor activity that allowed binding directly to thrombin, but D1 did not. The cofactor activity of the entire protein but not the mutants is increased in the presence of phospholipids and this is the only protein that binds to the phospholipid layer. These results indicate that the domain involving the epidermal growth factor-like structures of thrombomodulin is essential for thrombin binding and expression of the cofactor activity for protein C activation and that none of the extracellular domains interact with phospholipids.

Epidermal Growth Factor↗
PubMed1989

Low dose almitrine bismesylate improves pulmonary gas exchange during canine one-lung hypoxia.

The effects of low dose almitrine bismesylate on pulmonary gas exchange, venous admixture, and pulmonary perfusion were examined in a canine one-lung hypoxic model. The left lung was ventilated with 10.4% oxygen, 89.3% nitrogen, and 0.3% halothane, while the right lung was ventilated with 99.7% oxygen and 0.3% halothane. Group 1 (n = 8) was given no other drug for 60 min. In group 2 (n = 10), consecutive almitrine doses of 0.5, 1, and 2 micrograms/kg.min were administered iv for 20 min/dose. Blood gas and central hemodynamic values remained unchanged in group 1. In group 2, significant increases in PaO2 and significant decreases in venous admixture, dependent on the dose administered, were observed. Mean PaO2 increased from 222 +/- 78 (SD) to 292 +/- 75 torr, and mean venous admixture decreased from 22 +/- 7% to 18 +/- 6% at 2 micrograms/kg.min. Both the decrease in mean left pulmonary blood flow and the increase in mean right pulmonary blood flow were slight, although the cardiac output was unchanged. These results indicate that iv infusion of 2 micrograms/kg.min of almitrine weakly enhances pulmonary vasoconstriction in a hypoxic area and improves pulmonary gas exchange in a moderately hypoxic condition.

Almitrine↗
PubMed1989

[A comparative study of the depressive effects of halothane and isoflurane on medullary respiratory neurons in cats].

The depressive effects of halothane (H) and isoflurane (I) on the same respiratory neuron were studied in cats. Using a tungsten microelectrode, activities of medullary inspiratory neurons were recorded around nucleus ambiguus. The number of spikes (Spike) of each respiratory cycle and inter-spike interval (ISI) were measured. At 1 MAC, in 9 units out of 11, Spike was significantly fewer with I than with H. In 2 units out of 11, Spike was not significantly different between H and I. These results indicate that each respiratory neuron shows different sensitivity to H and I at 1MAC concentration. With increasing depth of anesthesia, Spike showed a concentration-related depression. During the course of respiratory depression, the spikes were 75.9 (1MAC), 63.3 (1.5MAC), 48.0 (2MAC), 24.2 (2.5MAC), 5.0 (3MAC) with H, and 77.4 (0.5MAC), 51.9 (1MAC), 23.5 (1.5MAC) with I. These spikes were completely depressed at 3.5MAC in H and 2MAC in I. Both H and I increased ISI with increasing depth of anesthesia. The effects of H and I on the phrenic nerve discharges closely resembled their effects on the respiratory neurons. We conclude that the respiratory depression produced by I exceeds that produced by equal MAC of H.

Animals↗
PubMed1989

[Optimum dose of intravenous butorphanol as a supplemental drug during regional anesthesia].

The optimum doses according to age of butorphanol tartrate as a supplemental drug during epidural and spinal anesthesia were investigated in 60 patients without complications. We classified patients into 4 groups by age as A, B, C and D-group. A-group consisting of patients between 20 to 40 years received 1.5mg of butorphanol. B-group 41-60, C-group 61-75 and D-group over 76 years received 1.0mg, 0.5mg and 0.25mg respectively. After operation was started without pain, and during the stable period, we determined by age, doses of butorphanol injected intravenously in one minute. HRs, mean BPs, respiratory rates (RRs) and so on were obtained at the preinjection point and 5 minutes after injection. In addition, in 15 patients, arterial blood gas analysis was performed at the same times. Butorphanol injections decreased HRs, mean BPs and RRs significantly. But there was no one whose PaCO2 increased more than 50 mmHg and no difference was found in degree of side effects between the groups. In conclusion, this study suggests that the decision to administer doses depending on the age is useful to decrease frequency of the grave side effects, especially respiratory depression which the elderly people frequently fall into.

Adult↗
PubMed1989

[The effects of intravenous lidocaine on the activity of medullary respiratory neurons in cats].

The effects of intravenous lidocaine on the activity of medullary respiratory neuron were studied in urethane anesthetized cats. Using a tungsten microelectrode, spikes from medullary inspiratory neurons were recorded around nucleus ambiguous. Lidocaine was administered using a constant-rate infusion pump until electrographic seizures appeared. The effect of lidocaine on the activity of respiratory neurons showed two types. In one type, consisting of 7 units out of 10, a sequence of changes was observed: the initial stage was represented by increased duration of the burst and decreased frequency of neural discharge; the second stage by desynchronization with mechanical lung inflation; the third stage by continuous activity and the forth stage by decreased spike activity and electrographic seizures. Blood concentration of the lidocaine was 9.6 +/- 3.5 micrograms.ml-1 at the second stage, 15.3 +/- 4.4 micrograms.ml-1 at the third stage, 26.6 +/- 4.1 micrograms.ml-1 at the fourth stage. In another type, consisting of 3 units out of 10, following administration of lidocaine the number of spikes showed only a concentration related depression. Blood concentration of the lidocaine was 6.9 +/- 2.7 micrograms.ml-1 when the spikes disappeared. These results indicate that intravenous lidocaine influences the respiratory rhythm and produces the respiratory depression working in the central nervous system.

Animals↗
PubMed1988

Phrenic nerve and vagal nerve activities during differential lung ventilation in cats.

The effect of differential lung ventilation (DLV) on afferent vagal and efferent phrenic nerve activities was studied in urethane anesthetized cats. One endotracheal tube was inserted into the left bronchus to ventilate its side lung. Another tube was inserted until its tip reached about 1 cm above the carina to ventilate the right lung. Using two respirators, each lung was ventilated independently. Using hooked silver electrodes, the vagal and phrenic nerve activities were recorded. The afferent vagal nerve was activated in concurrence with lung inflation at any ventilation rate. The right and left vagal nerves were activated by right and left lung ventilation, respectively. On the other hand, the right and left efferent phrenic nerves were synchronized, whether the ventilation was discussed or ventilation was achieved by right or left one lung ventilation or even by asynchronous DLV. The phrenic nerve activity was surpressed by one-lung, right or left, ventilation independently, so that the rhythm of the phrenic nerve was disturbed by asynchronous DLV. From these results, to reduce the stress of patients during asychronous DLV, it was considered that patients need heavier sedation than a usual mechanical ventilatory support.

Journal Article↗
PubMed1988

Activation of a brain-specific protein kinase C subspecies in the presence of phosphatidylethanol.

Protein kinase C (PKC) is normally activated by diacylglycerol in the presence of Ca2+ and phosphatidylserine. At physiological concentrations of Ca2+, however, phosphatidylethanol, a product of the phospholipase D-catalyzed transphosphatidylation reaction between membrane phospholipids and ethanol, can replace phosphatidylserine, and activate PKC. This mode of activation is most effective for the gamma-subspecies, which is expressed only in central nervous tissue. Phosphatidylmethanol is also effective to some extent. Consideration of these results suggests the possibility that ethanol may exert some effect on signal transduction in this tissue via changes in protein phosphorylation.

Animals↗
PubMed1988

The heterogeneity of protein kinase C in various rat tissues.

Expression of multiple subspecies of protein kinase C (PKC) was studied in various rat tissues. Three types of the enzyme designated type I, II, and III were analyzed, which have the structures of gamma-, beta- (beta I- and beta II-), and alpha-sequence, respectively. Type I enzyme was found only in the central nervous tissue, whereas type III enzyme appeared to be commonly present in various tissues such as liver, spleen, lung, testis, heart, and kidney. Type II enzyme was also found in these tissues. However, immunoblot and biochemical analysis indicated that type II enzyme of lung and heart was distinct from that of other tissues. The tissue-specific expression of PKC suggests that each subspecies of this enzyme has a defined function in processing and modulating tissue responses to external stimuli.

Animals↗
PubMed1988

Effects of caudal block with mepivacaine on resting ventilation and ventilatory response to carbon dioxide in sedated children.

We examined the effects of caudal anaesthesia using 10 mg.kg-1 of one or two per cent mepivacaine without epinephrine on resting ventilation, arterial blood gas tensions and the ventilatory response to carbon dioxide in 27 sedated children. Expired minute volume and respiratory frequency decreased significantly after the caudal blocks in both groups. PaO2 and PaCO2 remained unchanged in both groups. The slope of the CO2 response curve increased significantly in both groups. The mean plasma mepivacaine levels were 4.6 +/- 1.6 (SD) and 4.6 +/- 1.0 micrograms.ml-1 20 minutes after the caudal blocks with one and two per cent mepivacaine, respectively. These results demonstrate that resting ventilation is impaired but the ventilatory response to carbon dioxide is improved similarly by caudal block with one or two per cent mepivacaine.

Anesthesia, Caudal↗
PubMed1988

Functionally active thrombomodulin is present in human platelets.

We found functionally active thrombomodulin in human platelets (60 +/- 18 molecules per platelet). Protein C appeared not to be activated by thrombin with gel-filtered platelets. However, the activation of protein C by thrombin was accelerated by thrombin-stimulated and washed platelets. This cofactor activity of the platelets was neutralized by the anti-lung thrombomodulin-F(ab')2. From the Triton X-extract of platelets, thrombomodulin was partially purified by diisopropylphosphoryl-thrombin-agarose affinity chromatography. The Mr of the predominant platelet thrombomodulin was 78,000 before and 109,000 after reduction on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, values identical to those of placental thrombomodulin. The specific activity of the cofactor activity, apparent Kd (0.4 nM) for thrombin and Km (0.67 microM) for protein C of platelet thrombomodulin were also identical to those of placenta thrombomodulin. Thrombomodulin may play a role in activation of protein C on the surface of platelets.

Blood Platelets↗
PubMed1988

Identification of benidipine hydrochloride metabolites in rats and dogs.

A study of the metabolism of [14C]-(+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)- 1,4-dihydropyridine-3, 5- dicarboxylic acid (R*)-1-benzyl-3-piperdidinyl ester, methyl ester hydrochloride (14C-benidipine hydrochloride, 14C-KW-3049) revealed as major metabolic pathways oxidative N-dealkylation, hydrolysis of the ester moiety, dehydrogenation of the 1,4-dihydropyridine ring, hydroxylation of the methyl group and decarboxylation in rat and dog. Rat and dog showed similar metabolic pathways, but some quantitative differences were found between rat and dog.

Animals↗