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Biomedical subjects

H Okuda

Publications and source records attributed to H Okuda.

At least 235 records · Page 13Linked to original sources

[Primary effect of preoperative intra-arterial infusion chemotherapy in cervical cancer].

In order to obtain better prognoses for cervical cancer, we conducted preoperative intra-arterial (i.a.) infusion chemotherapy of CDDP in combination with AT-II pressor. Two courses of i.a. chemotherapy were performed for 67 patients with cervical cancer in stage IIb containing 54 squamous cell carcinomas and 13 adenocarcinomas before operation every 3 weeks. A histologically desirable effect in cervical lesion was obtained. A group given preoperative i.a. chemotherapy had a significantly lower rate of infiltration beyond uterus in comparison with 156 patients with 145 squamous cell carcinomas and 11 adenocarcinomas treated by surgery alone as the control group. Further, the rate of histological infiltration to parametrial edges after i.a. chemotherapy tended to be lower than the control group. From the above, it was considered that preoperative i.a. infusion chemotherapy of CDDP in combination with AT-II pressor for cervical cancer was effective as a neo-adjuvant chemotherapy.

Adenocarcinoma↗

Changes in the latency of the maximum positive peak of visual evoked potential during anesthesia.

The relationship between the latency of visual evoked potential (VEP) and the anesthetic concentration was investigated in surgical patients in order to examine the applicability of VEP in monitoring of the depth of anesthesia. The VEP was recorded with a standard EEG electrode from the midline parietal region in reference to both earlobes linked to the ground. An array of light-emitting-diodes mounted in opaque goggles was used to stimulate both eyes simultaneously and photic stimuli were delivered at random inter-pulse intervals with uniform distribution ranging from 2 to 5 seconds. Fifty trials of data were averaged to estimate that Pmax latency, i.e., the latent period from the photic stimulus to the maximum positive peak arising after 170 msec. Increases in the Pmax latency following the administration of anesthetics and restorations to preanesthetic values after recovery from anesthesia were found. A significant correlation was demonstrated between the Pmax latency and the inspiratory concentration of enflurane. The latency of the Pmax showed a drastic and a sensitive prolongation from about 200 msec in the awake state up to about 600 msec at the stage where the EEG exhibits large-voltage slow waves. Thus the measurement of the Pmax latency of VEPs was found to be useful for monitoring the depth of anesthesia.

Anesthesia↗

A quantitative analysis of hemodynamic effects of the right ventricle included in the circulation of the Fontan procedure.

BACKGROUND: Right heart hemodynamics were analyzed with a catheter-mounted velocity meter in seven patients after direct atrioventricular anastomosis for Fontan procedure (RV group) and were compared with those obtained in eight patients after direct atriopulmonary anastomosis (RA group). METHODS AND RESULTS: In the RV group, cardiac output was 2.7 +/- 0.6 l/min/m2; mean right atrial and pulmonary artery pressures were both 13 +/- 3 mm Hg; mean pulmonary artery wedge pressure was 7 +/- 5 mm Hg; left ventricular end-diastolic volume, determined angiographically, was 129 +/- 40% of normal; and its ejection fraction was 0.50 +/- 0.09. In the RA group, data were similar to those of the RV group except that right heart pressure were lower in the RV group, which was related to the preoperative condition of the pulmonary circulation. In the RV group, the fraction of ventricular forward flow of the total forward flow in the main pulmonary artery ranged from 0.21 to 0.46 and was not correlated with cardiac output or with any other parameter. The backward flow into the inferior vena cava at ventricular systole was greater than the atrial flow in two patients in whom cardiac output was less than 2.2 l/min/m2, whereas caval backward flow at atrial contraction was greater than ventricular flow in the other five patients, of whom four had a cardiac output greater than 3.1 l/min/m2. CONCLUSIONS: We conclude that the inclusion of right ventricle in the circulation of the Fontan procedure does not necessarily improve overall hemodynamics in most patients.

Adult↗

On the a. malaris of the goat (Capra hircus).

Detailed observations were made of the a. malaris in 25 adult goats by means of the acryl plastic injection method and the findings obtained were evaluated in comparison with those for other mammals. The malar artery arose from the superior wall of the infraorbital artery, lateral to the infraorbital nerve and superomedial to the maxillary tuber, independently or rarely in common with the superior alveolar artery. It first passed anterolaterally in the sulcus malaris on the superior surface of the lacrimal bulla and gave rise to the third palpebral branch independently or rarely in common with the inferior oblique muscular branch beneath the obliquus inferior muscle, and also the main and accessory inferior oblique and the maxillary sinus branches. The third palpebral branch gave off the periosteal, the conjunctive, the supero- and inferolateral branches. After the malar artery gave off the zygomatic branch on the orbital surface of the zygomatic bone, it passed anterosuperiorly up to the incisura malaris at the medial end of the infraorbital margin of the lacrimal bone and gave off the medial superior and inferior palpebral arteries or a common trunk between them. It continued to pass forwards as the nasal radical branch after giving off the infraorbital marginal branch and anastomosed with the nasal dorsal branch of the superficial temporal artery. The medial inferior palpebral artery formed the inferior palpebral arterial arch by anastomosing with the lateral inferior palpebral artery of the superficial temporal at the lateral canthus. The inferior palpebral marginal, the ocular orbicular muscular and the conjunctive branches diverged from the above arterial arch. The medial superior palpebral artery gave off the lacrimal canalicular and the nasolacrimal canal branches and anastomosed with the lateral superior palpebral artery or the frontal branch of the superficial temporal at the medial canthus. The characteristic features of the malar artery in the goat were thus the third palpebral branch occasionally diverging from the external ophthalmic artery of the maxillary artery, a main and several accessory inferior oblique muscular, the maxillary sinus branches and the zygomatic branches.

Animals↗

Role of Na+/H+ exchanger in insulin-stimulated glucose uptake into skeletal muscle.

Insulin-stimulated 2-deoxy-D-glucose uptake by the rat soleus muscle was concluded to be closely related to Na+/H+ exchanger from the following findings; (1) Insulin stimulated Na+ uptake by rat soleus muscle, (2) Amiloride inhibited the effect of insulin on 2-deoxy-D-glucose uptake by the muscle. (3) External Na+ or Li+ was essential for the action of insulin, and Na+ could not be replaced by other monovalent cations such as K+, Rb+, and choline+. The decreases in the effect of insulin on reduction of the pH of the medium, addition of amiloride, or solution for replacement of Na(+)-Hanks buffer by choline(+)-Hanks buffer could not be explained by decrease in specific binding of insulin.

Amiloride↗

DNA polymerase action blocked by adenine adducts induced by 5-hydroxymethylchrysene sulfate.

Modification of M13mp10 single-stranded DNA with 5-hydroxymethylchrysene (5HCR) sulfate, the ultimate carcinogenic metabolite of 5-methylchrysene, resulted in formation of N6[(chrysen-5-yl)methyl]adenine and N2[(chrysen-5-yl)methyl]-guanine at the ratio of 2.7:1. Measurement of DNA synthesis using this modified template and E.coli DNA polymerase I (Klenow fragment) demonstrated that increasing levels of adducts caused a progressive decline in replication. Analysis of reaction products on DNA-sequence gels revealed DNA elongation to be arrested exclusively at adenine adducts in -AAAGGA- and -AACA- sequences.

Adenine↗

Vascular effects of isosorbide dinitrate on the common carotid artery in human volunteers.

The effects of 20 mg of orally administered isosorbide dinitrate (ISDN, Isocoronal R; CAS 87-33-2) on cerebral hemodynamics were investigated in 14 normal healthy volunteers (average age 32.6 years). The common carotid artery hemodynamics in the right supraclavicular region were measured using an ultrasonic quantitative flow measurement system. 2 h after drug administration, systolic blood pressure (15.5 mmHg, p less than 0.001) and mean blood pressure (7.2 mmHg, p less than 0.02) decreased significantly, but diastolic blood pressure did not change. A decrease in blood flow volume (2.85 ml/s, p less than 0.001) and blood flow velocity (7.00 cm/s, p less than 0.001), and an increase in mean vessel diameter (0.19 mm, p less than 0.05), and volume elasticity (0.68 x 10(5) dyn/cm2, p less than 0.02) were observed with ISDN. Mean vessel diameter increased gradually and reached its maximum at 4 h. However, the other maximal effects of ISDN were exerted at about 2 h. The ultrasonic quantitative flow measurement system was found to be useful in the case of repetitive measurements of the common carotid artery hemodynamics. It has been demonstrated that ISDN (20 mg/subject, p.o.) increases the diameter of the common carotid artery, although it decreases the blood flow in the common carotid artery.

Adult↗

[A clinical study on endocervical type and endometrioid type cervical adenocarcinoma].

Seventy-seven patients with cervical adenocarcinoma were treated at the Department of Obstetrics and Gynecology, Okayama University Medical School from 1974 to 1987. Of these carcinomas, 42 (54.5%) were endocervical types and 35 (45.5%) were endometrioid types. Of the endocervical types 23.8% (10/42) were stage III-IV tumors, whereas 2.9% (1/35) of the endometrioid types were stage III-IV tumors (p less than 0.05). No significant differences were found between endocervical type and endometrioid type in the clinical background, the rate of lymph node involvement or the 5-year survival rate.

Adenocarcinoma↗

Phenobarbital does not increase early labeling of bilirubin from 4-[14C]-delta-aminolevulinic acid in man and rat.

delta-Aminolevulinic acid-4-[14C] and [3H]-bilirubin were administered intravenously to five patients with Gilbert's syndrome and four healthy control subjects on two occasions: before and on days 10 through 14 of a course of phenobarbital (2.5 mg/kg/day). The resulting curves of [3H]-bilirubin and [14C]-bilirubin in plasma were analyzed by computer to determine a number of parameters of physiological interest. As expected, phenobarbital produced a highly significant fall in the plasma concentration of unconjugated bilirubin as a result of a significant increase in hepatic bilirubin clearance in all subjects; plasma bilirubin turnover was unaltered. Surprisingly, the drug produced no change in the incorporation of [14C]-delta-aminolevulinic acid into [14C]-early labeled bilirubin. To explain this unexpected finding, the effects of phenobarbital (75 mg/kg/day for 6 days) on incorporation of [14C]-delta-aminolevulinic acid and 2-[14C]-glycine into [14C]-early labeled bilirubin and on the activity of the enzyme delta-aminolevulinic acid synthase were studied in nonfasted, adult, male Sprague-Dawley rats. At the dose and duration of treatment used, phenobarbital administration increased total hepatic delta-aminolevulinic acid synthase activity and produced a significant increase of 70% in the incorporation of [14C]-glycine into early labeled bilirubin. By contrast, no increase in the incorporation of [14C]-delta-aminolevulinic acid into early labeled bilirubin was observed. These data suggest that delta-aminolevulinic acid is an inappropriate precursor for studies of the rate of heme biosynthesis, presumably because it bypasses delta-aminolevulinic acid synthase, the physiological rate-limiting enzyme in the heme biosynthetic pathway.

Aminolevulinic Acid↗

[A clinicopathological study on adenocarcinoma of the uterine cervix].

A total of 102 cases of adenocarcinoma of the uterine cervix were reviewed to define the clinical and pathological behavior. In the 18 years between 1970 and 1987 the incidence of cervical adenocarcinoma increased. The rate of lymph node involvement in stage Ib was 16.1% (5/31) and in stage II 26.2% (11/42). There was no difference between the rate of lymph node involvement in adenocarcinoma and squamous cell carcinoma. The 5-year survival rates were as follows: stage I 83.3% (25/30), stage II 58.1% (18/31), stage III (0/4), stage IV (2/5), and all stages 64.3% (45/70). The 5-year survival rate for patients with adenocarcinoma was poor in contrast to that for patients with squamous cell carcinoma (p less than 0.05). It was suggested that adenocarcinoma was less radiosensitive than squamous cell carcinoma.

Adenocarcinoma↗

A new class of rat glutathione S-transferase Yrs-Yrs inactivating reactive sulfate esters as metabolites of carcinogenic arylmethanols.

A glutathione (GSH) S-transferase (GST), catalyzing the inactivation of reactive sulfate esters as metabolites of carcinogenic arylmethanols, was isolated from the male Sprague-Dawley rat liver cytosol and purified to homogeneity in 12% yield with a purification factor of 901-fold. The purified GST was a homo-dimeric enzyme protein with subunit Mr 26,000 and pI 7.9 and designated as Yrs-Yrs because of its enzyme activity toward "reactive sulfate esters." GST Yrs-Yrs could neither be retained on the S-hexylglutathione gel column nor showed any activity toward 1,2-dichloro-4-nitrobenzene, 4-nitrobenzyl chloride, and 1,2-epoxy-3-(4'-nitrophenoxy)propane. 1-Chloro-2,4-dinitro-benzene was a very poor substrate for this GST. 1-Menaphthyl sulfate was the best substrate for GST Yrs-Yrs among the examined mutagenic arylmethyl sulfates. The enzyme had higher activities toward ethacrynic acid and cumene hydroperoxide. N-terminal amino acid sequence of subunit Yrs, analyzed up to the 25th amino acid, had no homology with any of the known class alpha, mu, and pi enzymes of the Sprague-Dawley rat. Anti-Yrs-IgG raised against GST Yrs-Yrs showed no cross-reactivity with any of subunits Ya, Yc, Yb1, Yb2, and Yp. Anti-IgGs raised against Ya, Yc, Yb1, Yb2, and Yp also showed no cross-reactivity with GST Yrs-Yrs. The purified enzyme proved to differ evidently from the 12 known cytosolic GSTs in various tissues of the rat in all respects. Immunoblot analysis of various tissue cytosols of the male rat indicated that apparent concentrations of the GST Yrs-Yrs protein were in order of liver greater than testis greater than adrenal greater than kidney greater than lung greater than brain greater than skeletal muscle congruent to heart congruent to small intestine congruent to spleen congruent to skin congruent to 0.

Amino Acid Sequence↗

Induction of platelet Ca2+ influx and mobilization by a monoclonal antibody to CD9 antigen.

We found that a monoclonal antibody (MoAb) to CD9 antigen, PMA2, induced a rise in cytosolic free calcium concentration ([Ca2+]i) in fura-2-loaded platelets, and we examined whether this response was due to direct action of PMA2 on CD9 antigen. The rise in [Ca2+]i was dependent on the PMA2 concentration, irrespective of the presence or absence of extracellular Ca2+. The role of secreted adenosine diphosphate (ADP) and thromboxane in the [Ca2+]i response to PMA2 was studied using creatine phosphate/creatine phosphokinase (CP/CPK) and aspirin. Combined treatment with CP/CPK and aspirin abolished the rise in [Ca2+]i, although either CP/CPK or aspirin alone produced only partial inhibition. Inhibition of adenosine triphosphate (ATP) secretion and thromboxane B2 synthesis by an MoAb to the glycoprotein IIb-IIIa complex, PMA1, resulted in little [Ca2+]i response to PMA2. In contrast, thrombasthenic platelets, in which ATP secretion and thromboxane B2 synthesis were normal, showed a normal [Ca2+]i response. When PMA2 was added to CD9+ mononuclear cells, no rise in [Ca2+]i was observed. Thus, we conclude that binding of monoclonal immunoglobulin G molecules to the CD9 antigen raises [Ca2+]i through the effect of secreted ADP and thromboxane on platelets, and that CD9 antigen is not directly involved in induction of Ca2+ influx and mobilization.

Adenosine Triphosphate↗

Biomodulator-mediated susceptibility of endogenous lipid droplets from rat adipocytes to hormone-sensitive lipase.

The amount of fatty acid release by a fat cell homogenate without pretreatment with epinephrine was found to be slightly more than that released from fat cells by epinephrine, suggesting that fat cells contain high lipolytic activity even in the absence of lipolytic agents. Fat cells contain high hormone-sensitive lipase activity (1383 mumole free fatty acids/g/hr) in the absence of epinephrine, and addition of epinephrine to the cells did not increase the activity, significantly. Like epinephrine, DBcAMP and/or theophylline also elicited marked release of glycerol from fat cells without activating the hormone-sensitive lipase activity. However, although fat cells contain a large amount of hormone-sensitive lipase, lipolysis was negligible in the absence of these lipolytic agents. These results suggest that lipolytic agents such as epinephrine, DBcAMP, and theophylline induce lipolysis in fat cells through some mechanism other than activation of hormone-sensitive lipase and that in the absence of lipolytic agents, some system in fat cells inhibits lipolysis of endogenous lipid droplets by hormone-sensitive lipase. The lipid droplets in fat cells consist mainly of triglyceride with phospholipids, cholesterol, carbohydrate, and protein as minor constituents. The phospholipid fraction was found to consist of 75% phosphatidylcholine and 25% phosphatidylethanolamine. Of the minor constituents of endogenous lipid droplets, only phosphatidylcholine strongly inhibited hormone-sensitive lipase activity in a [3H]triolein emulsion. These results suggest that phosphatidylcholine in endogenous lipid droplets may be responsible for inhibition of hormone-sensitive lipase. Then, a cell-free system was established in which epinephrine, DBcAMP, and theophylline stimulated lipolysis of endogenous lipid droplets from fat cells by lipase solution. In this system, these lipolytic agents did not induce lipolysis in the absence of added lipase. Lipolysis in the mixture of the endogenous lipid droplets and lipase solution was accelerated by phospholipase C with concomitant loss of epinephrine-induced lipolysis. After pretreatment of the endogenous lipid droplets with phospholipase C, these lipolytic agents no longer induced lipolysis. Pretreatment of the endogenous lipid droplets with phospholipase C reduced their phospholipid content with the formation of phosphorylcholine, but did not affect their triglyceride and cholesterol contents. Treatment of the endogenous lipid droplets with phospholipase D did not affect lipolysis in the cell-free system. These results suggest that phosphatidylcholine in the endogenous lipid droplets may inhibit their lipolysis by hormone-sensitive lipase in fat cells and also be involved in the mechanisms of the stimulatory effects of epinephrine, DBcAMP, and theophylline on lipolysis.

Adipose Tissue↗

Propranolol-sensitive and phenoxybenzamine-insensitive binding of norepinephrine to endogenous lipid droplets from rat adipocytes.

Norepinephrine, epinephrine, and isoproterenol at concentrations of 5.5 x 10(-8) M were found to elicit lipolysis in a cell-free system containing lipid droplets from fat cells and lipase solution. In the cell-free system, the beta-blockers propranolol and dichloroisoproterenol at concentrations of 1 microM inhibited lipolysis induced by norepinephrine, whereas similar concentrations of the alpha-blockers phenoxybenzamine and yohimbine did not inhibit lipolysis. The binding of norepinephrine to endogenous lipid droplets was inhibited by propranolol, but not by phenoxybenzamine. We concluded that the propranolol-sensitive, phenoxybenzamine-insensitive binding of norepinephrine to endogenous lipid droplets is involved in lipolysis in fat cells. Treatment of endogenous lipid droplets with phospholipase C, but not phospholipase D, trypsin, chymotrypsin, or neuraminidase, inhibited the propranolol-sensitive binding of norepinephrine to the droplets. These results suggest that the phosphate group of phospholipid in endogenous lipid droplets may be the site of propranolol-sensitive binding of norepinephrine. The physiological significance of the propranolol-sensitive binding is discussed.

Adipose Tissue↗