Lipid peroxidation of parenchymal hepatocytes during cold preservation and after reoxygenation in rats.
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Animals↗
Biomedical subjects
H Inaba
Publications and source records attributed to H Inaba.
[Antitumor activity of BOF-A2, a new 5-fluorouracil derivative, against human cancers xenografted in nude mice by intermittent administration].
Antitumor effects of BOF-A2 given intermittently was evaluated with human gastric (H-111, H-83), colorectal (H-110, H-143) and lung (H-74, LC-376) cancers xenografted in nude mice and compared with those by continuous administration. BOF-A2 was orally given 3 or 4 times per week at 30 or 35 mg/kg over 4 weeks. This drug was effective to 5 strains except H-110 (IR > or = 58%), remarkably effective to H-81 and H-143 (IR > or = 80%) and caused tumor regression in mice bearing H-81 especially. Moreover, the drug was effective to H-74 which is rather insensitive to 5-FU and its known derivatives. When the drug was given orally to nude mice xenografted LC-376, 5-FU levels in the tumor tissue was notably durative for a long time as compared to UFT. It would be concluded that BOF-A2 was much effective to insensitive tumor to fluorinated pyrimidines or other anticancer, because of persistence of high levels of 5-FU in the tumor tissue. On the other hand, diarrhea which is caused by other fluorinated pyrimidines or consecutive administration of BOF-A2, was mild by the intermittent administration of BOF-A2.
Administration, Oral↗
Phase 1 study of L-627, biapenem, a new parenteral carbapenem antibiotic.
The safety and pharmacokinetics of L-627, a new injectable carbapenem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 20, 40, 80, 150, 300 and 600 mg of L-627 were administered by i.v. infusions over 1 hour. Plasma concentration-time profiles were well described with a two-compartment open model. The half-life of elimination from plasma was 1.3 +/- 0.8 (mean +/- SD) hour, and the Cmax and AUC paralleled the doses given. The mean urinary recovery of unchanged L-627 within the first 12 hours was 63.1 +/- 2.7% of the dose. In the multiple-dose studies, 300 mg of L-627 (i.v. over 1 hour) was administered every 12 hours, 11 times in total and 600 mg of L-627 was administered every 12 hours, 9 times in total. No discernible accumulation of the drug in plasma was observed. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject in one of the multiple-dose regimens (300 mg b.i.d.) showed only a slight elevation of transaminase value, although the elevated value promptly recovered after completion of dosing. No abnormality was observed in the other multiple-dose regimen (600 mg b.i.d.). From these results, L-627 was concluded to be safe and well tolerated.
Adult↗
Fluctuations in plasma levels of thrombomodulin in patients with DIC.
Plasma thrombomodulin (TM) has attracted considerable attention as a marker of endothelial cell membrane injury. We examined fluctuations in plasma TM levels in patients receiving therapy for the disseminated intravascular coagulation syndrome (DIC) using an enzyme immunoassay. Sixty healthy controls and 18 patients with DIC were studied. The mean +/- SD of the TM values initially measured immediately after the onset of DIC was 42.00 +/- 20.85 ng/ml, which was markedly increased as compared with the control value of 15.36 +/- 4.85 ng/ml (p < 0.001). Fluctuations in the TM levels over time were studied after dividing the patients according to the presence or absence of improvement in the underlying disease and improvement or lack thereof in the coagulation findings. Group I showed improvement in both categories, Group II showed improvement only in the latter, and Group III showed no improvement in either category. In Group I, the mean +/- SD of initial measured TM levels was 37.02 +/- 10.12 ng/ml and the mean of final values decreased to 58.9% of the initial value. This decrease was significant by paired Student's t-test (p < 0.01). The initial value in Group II was 45.86 +/- 18.86 ng/ml and the final values increased to 117.0% of the initial values, this difference was not significant. The initial value in Group III was 44.48 +/- 21.53 ng/ml and the final values increased to 143.4% of the former. This increase was significant by paired Student's t-test (p < 0.05). The difference in % fluctuations between Group I and Group III was significant by Wilcoxon's test (p < 0.01). These results suggest that the measurement of plasma TM can be useful in the management of DIC.
Adolescent↗
Chemiluminescence in the crude extracts of soybean seedlings. Postulated mechanism on the formation of hydroperoxide intermediates.
It has been reported that weak chemiluminescence (CL) from crude extracts of soybean seedlings is remarkably enhanced with the addition of various aldehydes (Biochim. Biophys. Acta 1058, 209-216). The reactivity of certain emitter(s) with oxygen species was examined in the autoclaved extracts of seedlings. When samples were reduced by the addition of hydrosulfite, two different types of reactivities in CL were defined. One type showed an initial rapid increase and a subsequent fast decay in CL upon mixing with oxygen. This rapid increase in CL intensity was independent of the presence of aldehydes, and was significantly suppressed by SOD. However, the subsequent slow decay phase in CL was dependent on the presence of aldehydes. In the sample reduced more moderately by borohydride, the same slow decay of CL appeared upon mixing with acetaldehyde and oxygen. This second type of CL was not inhibited by active oxygen scavengers. Hydrogen peroxide added to unreduced (oxidized) samples also elicited CL. Three types of primary emitters may be oxidized to form transient hydroperoxide, and excited for light emission by slightly different ways: two of them are excited by abstraction of one atomic oxygen from the hydroperoxy intermediate with aldehyde or hydrogen peroxide, leading to formation of an excited hydroxide intermediate. The third is excited directly on the binding of superoxide anion to the reduced primary emitter.
Acetaldehyde↗
Weak chemiluminescence of bilirubin and its stimulation by aldehydes.
Bilirubin in an alkaline solution exhibits a weak chemiluminescence (CL) under aerobic conditions. This spontaneous CL was markedly enhanced by the addition of various aldehydes. The fluorescent emission spectrum of bilirubin, excited by weak intensity light at 350 nm, coincided with its CL emission spectrum (peak at 670 nm). CL emission from bilirubin was not quenched by active oxygen scavengers. This suggests that triplet oxygen reacts with bilirubin, and forms an oxygenated intermediate (hydroperoxide) as a primary emitter (oxidative scission of tetrapyrrole bonds in bilirubin is not involved in this CL). The Ehrlich reaction (test for monopyrroles) and hydrolsulphite reaction (test for dipyrroles) on the CL reaction mixture and unreacted bilirubin showed no differences. When the CL was initiated by singlet oxygen, rather than superoxide anion, monopyrrole, was detected in the reaction products by gel chromatography. The inhibitory effect of a scavenger of singlet oxygen on CL was eliminated in the presence of formaldehyde. Therefore, triplet carbonyl, formed by singlet oxygen through the dioxetane structure in bilirubin, is not an emitter. The reaction mechanism of bilirubin CL and the formation of a hydroperoxide intermediate is discussed in relation to the chemical structure of luciferin molecules from bioluminescent organisms.
Acetaldehyde↗
Bilirubin chemiluminescence induced by the attack of active oxygen species.
Ultraweak chemiluminescence (CL) from bilirubin occurs in the presence of triplet oxygen and is stimulated by the addition of aldehydes. Active oxygen species also enhance bilirubin CL, in the absence of aldehydes. An inhibitory effect of active oxygen scavengers on the CL indicated that active oxygens generated from the decomposition of added hydrogen peroxide or from the xanthine-xanthine oxidase reaction contributed to the CL from bilirubin molecules. However, the contribution of singlet oxygen to the CL disappeared in the presence of formaldehyde. This suggested that the scission of tetrapyrrole bonds via a dioxetane intermediate or the production of triplet carbonyls from the oxidation of aldehydes by singlet oxygen was not involved in the CL, at least in the presence of formaldehyde. The spectrum of CL induced by the generation of active oxygen was the same as that from the aldehyde-enhanced CL reaction. We propose that the formation of a hydroperoxide (and/or hydroxide) bilirubin intermediate, but not a dioxetane, may be involved in the excitation of bilirubin molecules for CL.
Aldehydes↗
N-methyl-N'-nitro-N-nitrosoguanidine-induced light emission in Chinese hamster cell cultures: correlation with enhancement of chromosomal aberrations.
N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was found to induce an ultraweak photon emission in cultures of Chinese hamster fibroblasts (CHL). Measurements suggest that the light emission is due to a reaction between MNNG and cellular metabolites. The light emission depended on the concentration of MNNG and was oxygen-dependent, disappearing in a nitrogen atmosphere. Superoxide dismutase (SOD) or sodium azide decreased the emission intensity. The production of chromosomal aberrations in CHL by MNNG was correlated with the light emission intensity and was inhibited in the presence of SOD.
Animals↗
The amygdaloid kindling in developing, adult and aged rats.
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Aging↗
Low-level chemiluminescence and life span of Drosophila melanogaster.
Spontaneous photon emission (chemiluminescence, CL) as a monitor of free radical evolution in Drosophila melanogaster which had been maintained at 25 or 30 degrees C for 5 days after emergence was measured. When maintained at 30 degrees C the fly CL intensity was stronger than at 25 degrees C. Under the condition of the higher temperature, the fly life span was shorter (mean life span = 29 days at 30 degrees C and 63 days at 25 degrees C), and oxygen consumption (3.7 microliters/mg.h at 25 degrees C, 4.9 microliters/mg.h at 30 degrees C) and the mobility (movement distance = 25 mm/min at 25 degrees C, 700 mm/min at 30 degrees C) increased, together with augmentation of phospholipid hydroperoxide in the fly total lipids. The CL spontaneously emitted from fly homogenate was decreased by the free radical scavengers both in experiments in vivo and in vitro. The hypothesis is proposed that as the oxygen metabolism grows active, the chemiluminescent reactions that involve oxygen-dependent free radical metabolism, including membrane phospholipid hydroperoxidation, contribute to the acceleration of senescence of fly bodies.
Aging↗
Phosphoinositide hydrolysis and calcium mobilization induced by vasopressin and angiotensin II in cultured vascular smooth muscle cells.
The cellular action of vasoconstrictive hormones, angiotensin II (AII) and Arg8-vasopressin (AVP), on vascular smooth muscle (VSM) in cultured VSM cells from rat mesenteric artery was studied. Both AII and AVP specifically induce a transient increases in cytosolic free calcium independent of extracellular calcium or calcium channels activated by high potassium depolarization in VSM cells loaded with Fura-2. Vasoconstrictive hormones induce a dose-dependency with formation of inositolphosphates. Analysis using high pressure liquid chromatography has shown that AVP stimulates rapid and transient increases in inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate within 1 minute. Moreover, a laser-excitation fluorescence system reveals high calcium concentration sites in subsarcolemmal region. These results indicate that, unlike voltage-dependent calcium influx across the cell membrane, AII and AVP induce receptor-mediated increases in cytosolic free calcium via phosphoinositide hydrolysis creating an intracellular messenger for calcium release from intracellular calcium stores.
Angiotensin II↗
Flow cytometric DNA analysis of lung cancer cell lines.
Tumor DNA content (ploidy) was analyzed by use of flow cytometry (FCM) in 17 lung cancer cell lines which were subcultured in our laboratory. The study included 6 adenocarcinomas, 2 squamous cell carcinomas, 1 adenosquamous cell carcinoma, 5 large cell carcinomas, and 3 small cell carcinomas. Of the 17 lung carcinoma cell lines, 15 revealed aneuploid patterns with DNA index above 1.1, whereas one had diploid. The mean DNA index (DI) in adenocarcinoma, was 1.34 +/- 0.09, DI 1.6, in squamous cell carcinoma, DI 1.0 in adenosquamous cell carcinoma, DI 1.70 +/- 0.66 in large cell carcinoma, and DI 1.29 in small cell carcinoma. Of the 17 cell lines, three lines showed multiploid patterns with clinically poor prognosis and indicated heterogeneity. Flow cytometric DNA analysis using lung cancer cell lines could provide further basic study of lung cancer cells and give a useful information on the degree of the malignancy clinically.
DNA, Neoplasm↗
[[A dynamic model for populations reproduced by first marriage]].
Using data for Japan, the author analyzes "the effect of nuptiality and of marital fertility [on population trends and constructs] a population model in which childbearing occurs only within first marriage....First, we can prove that...we can construct a stable population theory based on nuptiality and marital fertility....Next..., we investigate the effect of [the age shift in first marriage patterns on total fertility rates], since delay of marriage has been thought to be one of [the] major causes for long-term fertility decline in Japan. We conclude that although [the age shift in first marriage patterns] could decrease Japanese fertility, its effect seems to be insufficient to induce such rapid fertility decline as is observed recently in Japan." (SUMMARY IN ENG)
Age Factors↗
Hydroxyl radical-induced characteristic chemiluminescent spectra from plasma of hemodialysis patients.
Plasma from hemodialysis patients evoked weak photon emissions (chemiluminescence) in a characteristic emission spectrum with a peak at 430 nm, attributed to attack by hydroxyl radicals generated from the iron-catalyzed breakdown of hydrogen peroxide (Fenton reaction), whereas plasma from normal healthy subjects showed a rather weak red chemiluminescence peak at around 680 nm, similar to that resulting from attack by hydroxyl radicals. However, the addition of hydrogen peroxide in the absence of divalent irons induced almost the same red chemiluminescent emission spectrum in both plasmas. The HPLC-gel-filtration chromatography carried out with both plasmas revealed that a primary emitter evoking a peak emission at 430 nm was located in the fraction of lower-molecular-mass substances in fractionated plasma from hemodialysis patients. In contrast, the elution peaks evoking red chemiluminescence with the addition of hydrogen peroxide were mainly observed for the higher-molecular-mass fraction, as determined by gel chromatography of both plasmas. Therefore, the observation of a chemiluminescence peak at 430 nm, induced by the generation of hydroxyl radicals, correlated well with chemiluminescent emissions in plasma samples from patients with chronic renal failure. Spectral analyses of clinical samples that show weak chemiluminescence by forced oxidation by such an active oxygen may provide a new and more sensitive method for diagnosing metabolic disorders.
Chromatography, Gel↗
[An experience of surgical treatment for catamenial pneumothorax with diaphragmatic and pulmonary endometriosis].
A case of catamenial pneumothorax with diaphragmatic and pulmonary endometriosis is presented. A 43-year-old, married woman had three times of recurrent right pneumothorax during the period from January to July on 1990. Each episode was apparently related to the onset of the menstruation suggesting catamenial pneumothorax. Right thoracotomy revealed a perforation of the diaphragm and five black spots on the visceral pleura. Involved portion both diaphragm and lung were excised. Microscopic examination of the excised specimens showed endometrial stroma in the diaphragm and subpleural layer of the lung. Although it has been postulated that intrathoracic endometriosis is a possible cause of the pneumothorax, very few cases have been reported in which pulmonary or pleural endometriosis was demonstrated histologically. Surgical and pathologic findings are documented discussing the relationship of both conditions in this report.
Diaphragm↗
[Age-related changes in nocturnal sleep: sleep architecture and sleep apnea, and the relationships between nocturnal sleep and mental function].
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Adult↗
[A case of anaplastic carcinoma of the mediastinal goiter].
We reported a case of anaplastic carcinoma of mediastinal goiter. The initial symptom was hoarseness, and thyroid scintigram and venogram revealed mediastinal thyroid malignant tumor, although cervical tumor could not be palpated. Operation was performed with median sternotomy. The size of the tumor was 8 x 6 x 3cm. Histological examination showed papillary adenocarcinoma of left lower pole of the thyroid gland which was transformed into anaplastic carcinoma and extended to the mediastinal cavity. Anaplastic carcinoma of mediastinal goiter is very rare, and our case showed anaplastic transformation from papillary adenocarcinoma.
Adenocarcinoma, Papillary↗
Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis.
To date it has been difficult to characterize completely a genetic disorder, such as hemophilia A, in which the involved gene is large and unrelated affected individuals have different mutations, most of which are point mutations. Toward this end, we analyzed the DNA of 29 patients with mild-to-moderate hemophilia A in which the causative mutation is likely to be a missense mutation. Using computer analysis, we determined the melting properties of factor VIII gene sequences to design primer sets for PCR amplification and subsequent denaturing gradient gel electrophoresis (DGGE). A total of 45 primer sets was chosen to amplify 99% of the coding region of the gene and 41 of 50 splice junctions. To facilitate detection of point mutations, we mixed DNA from two male patients, and both homoduplexes and heteroduplexes were analyzed. With these 45 primer sets, 26 DNAs containing previously identified point mutations in the factor VIII gene were studied, and all 26 mutations were easily distinguishable from normal. After analyzing the 29 patients with unknown mutations, we identified the disease-producing mutation in 25 (86%). Two polymorphisms and two rare normal variants were also found. Therefore, DGGE after computer analysis is a powerful method for nearly complete characterization of disease-producing mutations and polymorphisms in large genes such as that for factor VIII.
Base Sequence↗