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Biomedical subjects

Y Kikuchi

Publications and source records attributed to Y Kikuchi.

At least 757 records · Page 42Linked to original sources

[Transfer of cefotetan into exudates from excoriated skin wounds].

Transfer of cefotetan (CTT) into exudates from excoriated skin wounds was studied in 9 adult patients. Each subject was given an intravenous bolus injection of 50 mg/kg of body weight. Concentrations of CTT in serum and in exudate fluid were determined by bioassay using Escherichia coli NIHJ as the test organism. The mean (+/- S.D.) CTT concentration in serum reached 274.3 +/- 78.3 micrograms/ml at 30 minutes after the injection and decreased to 30.0 +/- 12.0 micrograms/ml at 8 hours after the injection. The peak value of CTT in exudate fluid was 143.1 +/- 22.3 micrograms/ml at 1 hour. Eight hours after the injection, the mean concentration in the exudate was 25.7 +/- 21.1 micrograms/ml. The data obtained were analysed pharmacokinetically: CTT concentrations in serum were analysed by two-compartment model, and those in exudate fluid from excoriated skin wounds were analysed by the model in which skin was considered as a small part of the peripheral compartment. Thus T1/2(beta) of CTT levels in serum was calculated as 2.38 hours, AUC0----infinity was 1,000.2 micrograms X hr/ml and Vd was 164.5 ml/kg. Tmax and Cmax of CTT levels in exudates were calculated as 1.05 hours and 131.2 micrograms/ml, respectively.

Adult↗

Establishment of a cisplatin-resistant human ovarian cancer cell line.

A cisplatin-resistant cell line was established by use of KF-1 cells derived from human serous cystadenocarcinoma of the ovary. This resistant cell line, designated "KFr," was capable of proliferating in the presence of 1.0 micrograms cisplatin/ml. It had doubling times of 24.8 and 27.2 hours in the presence of 0.5 and 1.0 micrograms cisplatin/ml, respectively. The KFr cells had lactate dehydrogenase (LDH) activities about fourfold higher than those of the parent KF-1 cells. Analysis of the isozymes of the KFr cells revealed that they had a faint LDH-3 band in addition to LDH-4, the only stained band in the parent KF-1 cells. The morphologic characteristics of the KFr cells were an enlarged nucleus and prominent nucleoli, unlike the nucleus and nucleoli of the parent KF-1 cells. The degree of resistance to cisplatin of the KFr cells was about twenty-fold higher than that of the KF-1 cells, with regard to the concentrations of cisplatin required for 50% inhibition of cell proliferation. However, when 5 microM calmodulin antagonists [N-(6-aminohexyl)-1-naphthalenesulfonamide or N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide] were added in the presence of concentrations of cisplatin that hardly inhibited cell proliferation, the KFr cell proliferation was markedly inhibited. These results suggest that cisplatin resistance can be overcome by calmodulin antagonists.

Calmodulin↗

[High position basilar top aneurysm treated via third ventricle].

There are two major approaches to basilar top aneurysm: one is subtemporal by Drake, another is pterional by Yasargil. In either approach, however, it is hazardous and difficult to approach basilar top aneurysm with megadolichobasilar anomaly because strong retraction of brain, nerve and vessel is required. A successful case of ruptured basilar top aneurysm with megadolichobasilar anomaly treated directly through the third ventricle is reported. A 62-year-old woman was admitted with consciousness disturbance. Plain CT scan on admission demonstrated massive and diffuse subarachnoid hemorrhage and a clot in the third ventricle. The left vertebral angiography demonstrated a 5 X 5 mm basilar top aneurysm with megadolichobasilar anomaly 24 mm distant from dorsum sellae. The aneurysm was considered to be inaccessible by conventional approaches because of its high position. Therefore, we have applied a new approach mentioned below. Operation was performed 2 days after the onset, using a bifrontal craniotomy. Dissecting interhemispheric fissure, we approached the third ventricle via lamina terminalis. Evacuating the clot in the third ventricle, the basilar top aneurysm was visualized. After dissecting the neck of aneurysm and perforators, clipping was performed. The postoperative course was uneventful. Surgical key points and prospective view in approaching via lamina terminalis and through the third ventricle for a high position basilar top aneurysm are discussed.

Basilar Artery↗

[Phase II study of (2''R)-4'-O-tetrahydropyranyldoxorubicin (THP) in patients with advanced gastrointestinal cancer--a report of the Tohoku THP Study Group].

A phase II study of THP was performed in patients with advanced gastrointestinal cancer. The dose schedule was 25 to 40 mg/m2 i.v./cycle repeated every 3 to 4 weeks. One partial (PR) and one minor response (MR) were achieved in 16 evaluable patients with stomach cancer. A case of PR had previously been shown to be resistant to doxorubicin and a case of MR resistant to aclarubicin, respectively. No objective responses were observed in 19 evaluable patients with other tumor sites in the gastrointestinal tract. Forty-eight patients were evaluable for toxic effects. Leukopenia (less than 4 X 10(3)/mm3) occurred in 54% of the patients and was dose-limiting. Thrombocytopenia (less than 10 X 10(4)/mm3) was less frequently observed (13%) than leukopenia. However, no cumulative marrow suppression was observed in repeated courses of the therapy. Non-hematologic toxic effects consisted of gastrointestinal disturbances (23%), hair loss (10%), general malaise (8%), fever (6%), ECG changes (4%) and hepatic dysfunction (2%). Further trials with a high dose schedule (40 mg/m2, q 3-4 weeks) in good-risk patients are necessary to validate the antitumor activity of THP against advanced gastrointestinal cancer.

Adult↗

Restorative effects of defective autologous lymphocyte cytotoxicity by calmodulin antagonists.

Reactivity of lymphocytes from paired living patients with ovarian carcinoma on autologous cancer cells was examined using six established cell lines. Although allogeneic lymphocytes had the capacity to lyse other cultured cancer cells, autologous lymphocytes were found to be unable to lyse their own cultured cancer cells. The defective activity of autologous lymphocytes was restored by preincubation of autologous target cells but not autologous effector cells with the calmodulin inhibitors W-5 or W-7.

Adenocarcinoma↗

Hairpin plasmid--a novel linear DNA of perfect hairpin structure.

The terminal structures of deletion derivatives of linear DNA killer plasmid from yeast were analyzed. The yeast Kluyveromyces lactis harbors two unique double-stranded linear DNA killer plasmids, pGKL1 of 8.9 kb and pGKL2 of 13.4 kb. The killer toxin and the resistance to the killer are coded by pGKL1, while pGKL2 is required for the maintenance of pGKL1 in the cell. When the pGKL plasmids from K. lactis were transferred into Saccharomyces cerevisiae by transformation, non-killer transformants harboring pGKL2 and new plasmids, F1 of 7.8 kb and F2 of 3.9 kb, were obtained. F2 was shown to be a linear DNA arising from a 5-kb deletion of the right part of pGKL1. F1 was an inverted dimer of F2. Here we show that F2 has two different terminal structures: one end has a protein attached at the 5' terminus whereas the two strands of duplex are linked together at the other end, thus forming a hairpin structure. This is a novel type of autonomously replicating DNA molecule.

Base Sequence↗

Bacterial examination of serous otitis media and experimental tubal stenosis.

Involvement of bacteria in serous otitis media was studied in man and by animal experimentation (using rabbits). Bacteria from the middle ear fluid, the skin of the external ear canal and the epipharynx of 100 human ears were cultured. Bacteria were also cultured from 50 ears of rabbits with serous otitis media induced experimentally by tubal stenosis, in the same way as those taken from human ears. Bacteria were detected in the middle ear fluid of 61 human ears (61%), and in 48 human ears (48%) except for those with contamination. The bacteria detected in the middle ear fluid were the same as those detected in the epipharynx in 40 of the 50 rabbit ears during the period from the start of treatment to the 30th day. In ears which were treated for more than 30 days, the bacteria detected in the middle ear fluid tended not to be the same as those detected in the epipharynx. From these results it was inferred that inflammation of the epipharynx spread over the middle ear cavity through the auditory tube.

Adolescent↗

A cruciform in the direct repeats of the yeast 2 micron DNA: Selective S1 nuclease cleavage at one of the three homologous palindromes.

An S1-hypersensitive site was found at the 60 bp direct repeats of the cis-acting, stability and/or copy number control region of the yeast 2 micron DNA in the supercoiled hybrid plasmid pDB248'. It was retained in a different plasmid, pYK2121, consisting of pBR322 and the 300 bp long repeated DNA. Analyses of 5'-end-labeled fragments and nucleotide sequence determination showed that the S1-cleavage site was at the central part of an AT-rich 19 bp palindrome present in the repeats. Two other homologous palindromes (21 and 15 bp) containing the 12 bp consensus sequences were not cleaved. The nucleotide sequences at the base of the stem and/or loop may determine the efficiency of the cruciform extrusion.

Base Sequence↗

Effect of clenbuterol on peripheral airway obstruction in bronchial asthma.

A study was carried out in 6 patients with bronchial asthma to investigate the effects of clenbuterol, a beta 2-sympathomimetic bronchodilator, on peripheral airway obstruction. The basal lung functions of the patients were almost within normal range in both vital capacity (VC) and forced expiratory volume in 1 second (FEV1), but their maximal flow rates were lower in effort-independent phase of both maximal expiratory flow volume (MEFV) curve and partial expiratory flow volume (PEFV) curve. Furthermore, they demonstrated marked basal frequency dependence of dynamic compliance [CL,dyn]. Oral administration of clenbuterol (40 micrograms) produced a significant increase in the maximal flow in effort-independent phase of both MEFV and PEFV curves, and markedly decreased frequency dependence of CL,dyn in comparison with the baseline values, while it improved both VC and FEV1 to a lesser extent. These results suggest that clenbuterol preferentially reduced the peripheral airway obstruction in bronchial asthma.

Adolescent↗

Chronic instrumentation and its lack of effect on the hemodynamics and regional myocardial blood flow of conscious dogs.

The effects of chronic instrumentation on regional myocardial performance and regional myocardial blood flow were studied in 8 mongrel dogs. Regional segment lengths were measured by an ultrasonic dimension gauge technique at two areas of the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX). Regional myocardial blood flow was measured by a tracer microsphere technique. These measurements were repeated while the animals were conscious on the 4th, 11th, 21st and 28th days after instrumentation. On the 4th day, the heart rate was rather high and regional shortening at both the LAD and LCX areas remained suppressed. After the 11th day, hemodynamic variables such as heart rate, left ventricular pressure and regional wall motion were fairly constant. Regional myocardial blood flow and its distribution were also constant throughout the experimental period. Fibrosis of the epicardium invariably induced by surgical procedures did not affect the distribution of regional blood flow as compared with that of the interventricular septum. Thus, a stable hemodynamic state was recorded after the 11th day following surgical manipulation and the implantation of sensors and catheters did not affect the level of regional myocardial blood flow or its distribution at rest. Such long term reproducible measurements of regional wall motion and regional myocardial blood flow may facilitate chronic studies of cardiovascular physiology.

Animals↗