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Biomedical subjects

Y Sekine

Publications and source records attributed to Y Sekine.

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

Frameshifting is required for production of the transposase encoded by insertion sequence 1.

Insertion sequence IS1 has two coding frames, insA and insB, which are essential for its transposition. Here, we show that a frameshifting event in the -1 direction from the 3' end region of the insA frame to an open reading frame (B' frame), extending from the 5' end of the insB frame, is involved in production of the InsA-B'-InsB fusion protein that has IS1 transposase activity. The frameshifting event is likely to have occurred at the sequence AAAAAC where the insA frame overlaps the B' frame. Interestingly, this sequence is also present in one of the two sequences identified in retroviruses as frameshift signals for production of transframe polyproteins from the overlapping genes gag-pro or gag-pro-pol.

Amino Acid Sequence↗
PubMed1989

Use of antisera in the isolation of human specific conjugates of haloperidol.

1. Three conjugated metabolites of haloperidol were isolated from urine of patients on haloperidol and purified by h.p.l.c. with immunological detection, using three types of anti-haloperidol antisera. 2. Structures of the metabolites were: a sulphate conjugate of the 2-hydroxylated 4-fluorophenyl ring of reduced haloperidol (MH-1), a glucuronide conjugate at the same position as MH-1 (MH-2), and a glucuronide conjugate of the hydroxy group of haloperidol (MH-3). 3. MH-3 was the main urinary metabolite in volunteers receiving haloperidol, who excreted 18% of the dose in the 24 h urine as MH-3, while other conjugates were less than 1%. MH-3 could not be hydrolysed with beta-glucuronidase, due to steric hindrance. 4. Immunological detection of conjugated metabolites is very useful in metabolic studies in humans because of its sensitivity and specificity.

Adult↗
PubMed1989

[Cardiocirculatory disturbances after surgery of carcinoma of the thoracic esophagus].

From 1976 to 1985, 277 cases of carcinoma of the esophagus were resected in the Second Department of Surgery, Tohoku University School of Medicine. Postoperative cardiocirculatory disturbances occurred in 114 cases (41.2%), arrhythmia being the disturbance most frequently observed (86.8%). Low cardiac output syndrome occurred in 8 cases and myocardial infarction occurred in 3 cases. The majority of the cases were treated successfully, but 5 patients died within one month after operation. Causes of death were as follows: myocardial infarction, constrictive pericarditis, cardiac tamponade, non-occlusive mesenteric ischemia and acute cardiac failure. Postoperative arrhythmia occurred mainly up to the third postoperative day. Low cardiac output syndrome occurred just after operation or on the first postoperative day. All cases of myocardial infarction occurred on the first postoperative day. The rate of occurrence of cardiocirculatory disturbances in aged patients (greater than or equal to 70) was significantly higher than other group (less than or equal to 69), (56.7%:38.1%, p less than 0.05). The rate of occurrence of cardiocirculatory disturbances in patients who had a history of hypertension or in patients with abnormal preoperative electrocardiographic findings were relatively higher than those in patients who had no history of hypertension or in patients with no abnormal preoperative electrocardiographic findings. The rate of occurrence of cardiocirculatory disturbances in patients who had undergone total resection of the thoracic esophagus was significantly higher than that in patients who had undergone partial resection of the thoracic esophagus (42.8%:23.8%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Interaction of enoxacin with theophylline in rats.

Enoxacin (ENX) has been reported to raise significantly plasma levels of theophylline (TP) in humans. In order to elucidate a mechanism of this interaction, in vivo and in vitro studies were carried out in rats. Concomitant dosing of ENX with TP significantly elongated plasma elimination half-life of TP, which led to a marked increase in the maximum plasma TP level after repeated administrations of both drugs. In rats treated with ENX, urinary excretion of unchanged TP increased and that of TP metabolites comparably decreased. The pharmacokinetic analysis showed that ENX did not change renal clearance of TP and these observed effects of ENX were attributed to reduced metabolic clearance of TP. In the in vitro studies by using liver microsomes, ENX reduced the magnitude of the type II difference spectral interaction of TP with cytochrome P-448 (P-448) and the formation of TP metabolites catalyzed by P-448. These results strongly suggest that the inhibition of the TP binding to the ferric iron of P-448 leads to that of the TP metabolism. The most essential site of ENX to inhibit the TP metabolism was found to be the 4'-nitrogen atom in the 7-piperazinyl group, and the stereochemical structure of ENX was suggested to be responsible for this inhibition.

Animals↗
PubMed1989

[Clinical analysis of postoperative recurrent nerve palsy in patients undergoing operation of carcinoma of the thoracic esophagus].

From January 1976 to April 1987, 325 cases of carcinoma of the thoracic esophagus were resected in our department. Among these cases, 25 cases were not included because of direct operative deaths or early hospital deaths, and 300 cases were selected for clinical analysis of postoperative recurrent nerve palsy, which occurred in 75 cases (25.0%). The rate of occurrence of this palsy in the last 6-year period was higher than that in the first 6-year period (34.0% and 15.3%, respectively). It was suggested that the extension of surgical procedures to the cervix and upper mediastinum had contributed to this increase in rate. The sides affected by palsy were as follows: left, 56.0%, right 12.0%, bilateral, 24.0%; unknown, 8.0%. The importance of gentle handling of the left recurrent nerve during operation should be emphasized. The rate of occurrence of palsy in the cases of "Iu" was higher than in cases of "Im" and "Ei" (53.3%, 31.6%, 26.8%, respectively). The rate of occurrence of this palsy was significantly higher in the cases in which cervical anastomosis was performed than in cases in which intrathoracic anastomosis was performed (31.9% and 2.8%, respectively; p less than 0.01). Of the cases complicated by this palsy (Group A), tracheostomy was done in 12.0% of the cases and long-term transnasal tracheal tube cannulation or tube reinsertion done in 29.3%. These rates were significantly higher than the rates for cases who did not develop this palsy (Group B). The rates of occurrence of postoperative pulmonary complications within one month after surgery in Group A and Group B were almost same (24.3% and 21.8%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Determination of L-6-keto-piperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202), a new analog of thyrotropin-releasing hormone, in plasma by radioimmunoassay.

A sensitive and specific radioimmunoassay has been developed for the determination of L-6-keto-piperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202), a new analog of thyrotropin-releasing hormone (TRH), in plasma. An antiserum was produced in guinea pigs immunized with RGH-2202 which was conjugated to bovine serum albumin by an N-succinimidyl ester method. Iodine-125 labeled L-6-keto-piperidine-2-carbonyl-L-leucyl-L-prolyltyramine [( 125I]RGH-2202) was used as a tracer. Polyethylene glycol was used to separate bound and free [125I]RGH-2202 in the reaction mixture. The assay of RGH-2202 in plasma was possible over a concentration range from 0.1 to 6.4 ng/ml, using 0.1 ml of plasma without the need for an extraction procedure. The antiserum used for the assay was highly specific for RGH-2202, and did not cross-react with TRH and the hydrolyzed derivatives of RGH-2202 such as L-6-keto-piperidine-2-carbonyl-L-leucyl-L-proline, L-6-keto-piperidine-2-carbonyl-L-leucine and L-leucyl-L-proline amide, which were assumed to be present in plasma as metabolites. The coefficients of variation were 4.6-6.7% for within-assay and 6.0-8.8% for between-assay. Plasma levels of RGH-2202 in rats were determined after an intravenous administration of RGH-2202 at a pharmacologically effective dose (0.625 mg/kg).

Animals↗
PubMed1988

[Bronchial arterial infusion of lymphokine-activated killer cells stimulated by autologous tumor cells].

Bronchial arterial infusion (BAI) of Lymphokine activated killer (LAK) cells, stimulated in vitro by autologous tumor cells, was performed for a primary lung cancer patient, a 47-year-old male patient with primary squamous cell carcinoma of the lung who underwent probe thoracotomy and had part of the tumor tissue removed. Peripheral blood lymphocytes were cultured in 500 U/ml of recombinant IL-2(Shionogi Pharm. S6820) for 9 days after in vitro stimulation with mitomycin C-treated primary tumor cells for 3 days. These cells (designated St-LAK cells) were inoculated from the bronchial artery of patients who received 60 Gy irradiation of the primary site and mediastinal lymph nodes. The tumor regressed significantly from 8 X 7 to 3 X 2.5 cm in diameter. The advantages of LAK-BAI using St-LAK cells with irradiation were discussed.

Bronchial Arteries↗
PubMed1988

Pharmacokinetics of an active cadralazine metabolite in plasma and blood vessels of spontaneously hypertensive rats.

The plasma and blood vessel (aorta and mesenteric artery) levels of (+/-)-6-[ethyl(2-hydroxypropyl)amino]-3-hydrazinopyridazine (ISF-2405), an active metabolite of cadralazine, were determined and compared with the changes in blood pressure in spontaneously hypertensive rats after single oral administration of cadralazine. The mean plasma level of ISF-2405 reached a maximum at 0.5 h after oral administration of 3 mg/kg of cadralazine, followed by a rapid elimination with a half-life of 1.0 h, whereas the mean aorta level of ISF-2405 reached a maximum at 4 h after dosing, followed by a slow elimination with a half-life of 6.5 h. The mean mesenteric artery levels of ISF-2405 were almost the same as the mean aorta levels over the time investigated. Both patterns of aorta and mesenteric artery levels of ISF-2405 were in good agreement with those of the hypotensive effects. These findings substantiate the assumption that the slow onset and long duration of the pharmacological effect of cadralazine is closely related to the distribution pattern of the active metabolite ISF-2405 in blood vessels, a target tissue of antihypertensive vasodilator drugs.

Animals↗
PubMed1987

Determination of ISF-2405, an active metabolite of cadralazine, in plasma and tissues by radioimmunoassay.

A radioimmunoassay has been developed which makes possible sensitive and specific determination of an active metabolite of cadralazine, (+/-)-6-[ethyl(2-hydroxypropyl)amino]-3-hydrazinopyridazine (ISF-2405), in plasma and tissues. On account of its lability in a sample solution, ISF-2405 in biological samples was selectively derivatized to a stable form, (+/-)-6-[ethyl(2-hydroxypropyl)amino]-3-(3,5-dimethyl-1-pyrazolyl) pyridazine (ISF-3349), by treatment with acetylacetone. The concentration of ISF-2405 was determined by the assay of the resultant ISF-3349. Antiserum against ISF-3349 was elicited in guinea pigs immunized with the ISF-3349 derivative coupled with bovine serum albumin. The obtained antiserum was highly specific for ISF-3349, and did not cross-react with either cadralazine or its metabolites. [Pyrazole-4-3H]labeled ISF-3349 with a specific activity of 13.9 Ci/mmol was used as the radioligand. Assays of ISF-2405 in plasma and tissues were possible over the concentration range from 0.4 to 6.4 ng/ml with 1 ml of plasma, and from 2 to 64 ng/g with 100 mg of tissue. Plasma and blood vessel levels of ISF-2405 in rats after single oral administration of cadralazine have also been determined by the present method.

Animals↗