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Biomedical subjects

Y Kurata

Publications and source records attributed to Y Kurata.

At least 181 records · Page 10Linked to original sources
PubMed1989

Modification by sodium L-ascorbate, butylated hydroxytoluene, phenobarbital and pepleomycin of lesion development in a wide-spectrum initiation rat model.

Rats were treated for 1 week each with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 0.2% N-bis(2-hydroxypropyl)-nitrosamine (DHPN) and 0.2% N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the drinking water, and then administered diet containing 5% sodium L-ascorbate (Na-AsA), 1% butylated hydroxytoluene (BHT) or 0.05% phenobarbital (PB), or weekly intraperitoneal injections of 2 mg of pepleomycin per kg body weight until week 36. Histopathological examination revealed that all exerted significant modulation effects on tumor development in the various target organs. Na-AsA was found to inhibit liver but promote renal pelvis and bladder carcinogenesis. BHT similarly decreased liver and enhanced bladder lesion development. PB, in contrast promoted hepatocarcinogenesis. However both PB and BHT were associated with increased incidences of adenomas and adenocarcinomas of the thyroid. Thus the wide-spectrum initiation model allowed confirmation of site-specific modification potential and in addition demonstrated potentiation of kidney and bladder carcinogenesis promotion by pepleomycin.

Animals↗
PubMed1989

Lack of carcinogenicity of quercetin in F344/DuCrj rats.

Quercetin was administered at dietary levels of 0(control), 1.25 and 5.0% to groups of 50 male and 50 female rats for 104 weeks, and then all animals were maintained without quercetin supplement for a further 8 weeks. At 5.0% quercetin, both sexes showed growth retardation throughout the study. There were no treatment-ascribed effects regarding clinical signs, mortality, urinalyses or hematology. Although serum glucose in 5.0% quercetin-treated males was significantly decreased and some relative organ weights in 5.0% groups showed statistically significant increases, these latter changes seemed to be related to the growth retardation. An increased incidence of non-neoplastic hyperplastic polyps in the cecum was noted in the 5.0% males. The incidences of cystic changes and fibroadenomas of the mammary gland, and foci (areas) of hepatocellular alteration in the 5.0% females, and liver bile duct proliferations in the 5.0% males were significantly decreased. No proliferative lesions of the urinary bladder related to treatment with quercetin were found in any rats. The incidences of several other nonneoplastic and neoplastic lesions which demonstrated statistically significant changes appeared to be related to the growth retardation or to be within the normal range, and therefore none was considered to be significant biologically. Thus, the investigation did not demonstrate any clear carcinogenic effect of quercetin on F344 rats at dietary levels of up to 5.0%.

Animals↗
PubMed1989

Immunochemical characterization of an autoantigen on platelet glycoprotein IIb in chronic ITP: comparison with the Baka alloantigen.

Employing an immunoblotting procedure, we have identified and characterized an autoantigen carried on glycoprotein (GP) IIb in a patient with chronic idiopathic thrombocytopenic purpura (ITP), and have compared the location of the autoantigen with that of the platelet-specific alloantigen Baka. Immunoblots, using the partially purified GP IIb/IIIa complex as the target antigen, indicated that GP IIb alpha carried both the ITP autoantigen and the Baka alloantigen. The ITP plasma contained another antibody against a 100 kD protein (P100), a trace contaminant in the GP IIb/IIIa sample, which is probably a proteolytic fragment of an internal 124 kD protein. After chymotrypsin treatment, the auto- and alloantigen were found to be located on 65 kD fragments detectable under reducing conditions. In addition, immunoblots made after two-dimensional nonreduced-reduced SDS-polyacrylamide gel electrophoresis (SDS-PAGE) directly demonstrated that both 65 kD fragments had a molecular weight of 80 kD under nonreducing conditions; this provides evidence that these fragments were one and the same, and were derived from GP IIb alpha. Immunoblots of platelets digested in situ with chymotrypsin indicated that the 65 kD fragment of GP IIb alpha was retained by the platelet membrane. We conclude, therefore, that a 65 kD fragment, which represents the membrane side of the chymotrypsin cleavage site on GP IIb alpha, carries a clinically important determinant(s) recognized not only by the anti-Baka alloantibody, but also by the ITP autoantibody.

Adult↗
PubMed1989

New approach to eliminate HLA class I antigens from platelet surface without cell damage: acid treatment at pH 3.0.

A new method was studied for eliminating HLA class I antigens from the surface of platelets without damaging the cells. Platelets were exposed to an acid solution (pH 3.0) to eliminate the antigenicity of HLA class I antigens. The reduction in antigenicities of HLA class I common antigen and individual HLA class I antigens by acid treatment was marked. Patients' sera which contained multispecific HLA antibodies reacted with PBS-treated platelets, but not with acid-treated platelets. No changes were observed in the antigenicities of glycoprotein Ib or glycoprotein IIb/IIIa. The viability of acid-treated platelets was 83%. Ultrastructural investigations revealed no significant difference between the PBS-treated platelets and acid-treated platelets. The platelet function studies showed that the aggregation of acid-treated platelets induced by various agonists was only slightly reduced compared with PBS-treated platelets. We propose that acid-treated platelets are promising for clinical use in patients refractory to platelet transfusions and may be superior to chloroquine-treated platelets for analysis of the specificity of antiplatelet antibodies.

Blood Platelets↗
PubMed1989

Membrane actions of ethanol on rabbit sino-atrial node studied by voltage clamp method.

Electrophysiological effects of ethanol on rabbit sino-atrial node were studied by means of the double-microelectrode voltage clamp method. In spontaneously beating preparations, ethanol (above 1%) decreased the maximum rate of depolarization of the action potential. Furthermore, 3% ethanol produced a significant decrease in the action potential amplitude, the action potential duration at 50% repolarization and the rate of the diastolic depolarization. Of the current systems, voltage clamp studies showed that ethanol reduced the slow inward current, the time-dependent potassium outward current and the hyperpolarization activated inward current. These observations indicate that ethanol does not have an effect on a single current system, but directly modifies the spontaneous discharge of sino-atrial node pacemaker cells due to a reduction of the time-dependent current systems.

Action Potentials↗
PubMed1989

[Modifying effects of beraprost sodium (TRK-100) on N-methyl-N-nitrosourea (MNU) carcinogenesis in F344 rats].

The potential tumor-promoting effects of beraprost sodium (TRK-100), stable analogue of prostacyclin (PGI2), were investigated in rats pretreated with N-methyl-N-nitrosourea (MNU) which is a potent initiator of tumor development in a variety of organ or tissues. Male F344 rats were initially given injections of MNU (20 mg/kg b.w. i.p.) twice a week for 3 weeks, and then administered drinking water containing 6, 2, 0.7 or 0.2 ppm of beraprost sodium for the next 29 weeks. For comparison, positive control groups received N-propyl-N-nitrosourea (PNU), which is a carcinogen in hematopoietic system and small intestine on F344 rat, at the dose of 200, 50 and 12.5 ppm in their drinking water. Appropriate non-treated controls were also included. Numerous tumors were observed in many organs including the hematopoietic system, digestive tract, nervous system, Zymbal's gland (auditory sebaceous glands) and peritoneal mesothelium. However, no tumor-enhancing effects of beraprost sodium were observed. In contrast, the groups treated with PNU demonstrated increased development of tumors in the tongue, forestomach, large intestine and Zymbal's gland. These results thus indicate that beraprost sodium is not capable of modulating the development of MNU-induced tumors.

Animals↗
PubMed1989

[Comparative studies on an autoantigen in ITP and the Baka alloantigen on platelet membrane glycoprotein IIb].

Platelet membrane glycoprotein (GP) IIb carries not only the Baka alloantigen but also an autoantigen in some patients with chronic idiopathic thrombocytopenic purpura (ITP). We previously reported one ITP patient (RY) with anti-GPIIb autoantibody in her plasma. In this report, we investigated whether the epitope of the autoantigen on GPIIb (case RY) is identical to that of the Baka alloantigen or not. The anti-Baka antibody used in this study was obtained from a mother with a child suffering from neonatal alloimmune thrombocytopenic purpura as reported by Okada et al. Immunoblotting showed that the anti-Baka antibody bound to GPIIb from Baka-positive platelets only. In contrast, the anti-GPIIb autoantibody in RY plasma bound to GPIIb, irrespective of Baka phenotype. In addition, after neuraminidase treatment of GPIIb on nitrocellulose paper, the anti-Baka antibody failed to bind to Baka-positive GPIIb, while the autoantibody still bound to GPIIb. From these data, we conclude that the epitope of the autoantigen in RY patient is different from that of the Baka alloantigen.

Antigen-Antibody Reactions↗
PubMed1989

[Immunochemical characterization of platelet-specific alloantigen Baka].

We investigated the location of platelet-specific alloantigen Baka on platelet membrane glycoproteins. In indirect immunoprecipitation experiments, the anti-Baka antibody precipitated glycoprotein (GP) II b and a small amount of GP III a. The immunoblots using partially purified GP II b/III a complex as the target antigen indicated that GP II b alpha carried the Baka alloantigen. When the partially purified GP II b/III a complex digested with chymotrypsin was examined, the Baka alloantigen was found on a 65 kD fragment derived from GP II b alpha under reducing conditions. In addition, the immunoblots after two-dimensional nonreduced-reduced SDS-PAGE directly indicated that the 65 kD fragment had a mol. wt. of 80 kD under nonreducing conditions. The immunoblots using platelets digested in situ with chymotrypsin indicated that the 65 kD fragment of GP II b alpha was retained by the platelet membrane. We conclude, therefore, that the Baka alloantigen is located on a 65 kD fragment that represents the membrane side of the cleavage site of chymotrypsin on GP II b alpha.

Antigens, Human Platelet↗
PubMed1989

[Test for anti-platelet antibody].

A number of methods have been established to detect platelet antibodies. This paper reviews the different methodologies that were developed to detect plasma anti-HLA antibodies and platelet specific antibodies, and their clinical usefulness. In addition, recent advances in platelet specific antigens and the methods to discriminate between anti-HLA antibodies and platelet specific antibodies are described.

Blood Grouping and Crossmatching↗
PubMed1988

L-ascorbic acid amplification of second-stage bladder carcinogenesis promotion by NaHCO3.

The dose dependence of NaHCO3 promotion of urinary bladder carcinogenesis and the effects of additional L-ascorbic acid (AsA) administration were investigated subsequent to initiation. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then, starting 3 days after cessation of carcinogen treatment, received basal diet containing NaHCO3 at levels of 0, 0.375, 0.75, 1.5, and 3.0% with or without a 5% AsA supplement for 32 weeks. NaHCO3 dose-dependently increased the incidence and numbers of urinary bladder carcinomas in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine. 5% AsA, while itself exerting no promoting effect, amplified the enhancing influence of NaHCO3 on induction of urinary bladder carcinomas. The same dose-dependent elevation of urinary pH and Na+ concentration was associated with NaHCO3 treatment with or without AsA. NaHCO3 significantly increased DNA synthesis in the urinary bladder epithelium and the additional treatment with AsA was associated with a significant further elevation. Thus, increased urinary pH and Na+ concentrations appear to play important roles in NaHCO3 promotion and AsA amplified this promotion. NaHCO3 treatment, with or without AsA, induced cellular proliferation, although it is unclear whether this is an essential factor.

Animals↗
PubMed1988

Modification of N-methyl-N'-nitro-N-nitrosoguanidine-induced forestomach and glandular stomach carcinogenesis by phenolic antioxidants in rats.

The modifying effects of five phenolic antioxidants on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated forestomach and glandular stomach carcinogenesis were investigated in male F344 rats. Groups of 20 rats were given an intragastric dose of 150 mg/kg body weight MNNG, and starting from 1 week later received diet supplemented with 0.8% catechol (CC), 1.0% 2-tert-butyl-4-methylphenol, 1.5% p-tert-butyl-phenol, 1.5% methylhydroquinone, 1.5% 4-methoxyphenol (4MP), or basal diet alone for 51 weeks. Further groups of 10-15 rats were maintained as controls without prior treatment with MNNG. The incidences of squamous cell carcinoma of the forestomach in MNNG-treated animals were significantly elevated by the diets containing CC (P less than 0.001), 2-tert-butyl-4-methylphenol (P less than 0.001), or p-tert-butylphenol (P less than 0.01), while the development of carcinoma in situ was inhibited by 4MP (P less than 0.01). Treatment with CC, 2-tert-butyl-4-methylphenol, p-tert-butylphenol, or 4MP alone induced forestomach hyperplasia at incidences of 86.7, 40, 93.3, and 100%, respectively. In the pyloric region of the glandular stomach, the development of adenomatous hyperplasia and adenocarcinoma after MNNG treatment was significantly enhanced by diet containing CC (P less than 0.001). Moreover, treatment with CC alone induced 100% adenomatous hyperplasia and induced adenocarcinoma in 20% of animals. These results clearly demonstrated that while antioxidants causing proliferation in forestomach epithelium can markedly enhance carcinogenesis in this tissue, others displaying the same or greater potential for generating a hyperplastic response, like 4MP, can exert an inhibitory effect. In addition, it was shown that CC, which is widely present in our environment, is an unequivocal glandular stomach carcinogen also possessing strong enhancing activity for MNNG-induced lesion development.

Animals↗
PubMed1988

A novel system of LDL apheresis combining a centrifugal plasma separator with a specific LDL adsorption column.

A novel system of low density lipoprotein (LDL) apheresis for familial hypercholesterolemia (FH) was developed, combining a centrifugal plasma separator (IBM-2997) with a new adsorption column specific to lipoproteins containing apolipoprotein B (apo-B), and its operation was compared to previous methods. The present system selectively removed LDL without the substantial reduction of high density lipoprotein that was seen with other methods using membrane filters. The capacity for LDL removal was slightly more reduced with the adsorption column than with the membrane filters when a single column was used. Since the ability to obtain plasma in the centrifugal system was much higher than in the system using membrane filters for plasma separation, efficient apheresis could be performed in a much shorter time, without making an arterio-venous shunt. Remixing of blood cells, such as platelets, with the separated plasma sometimes raises the pressure within the plasma component separator, but the problem could be avoided by withdrawing the buffy coat fraction, using the WBC pump of the IBM separator. In conclusion, the novel system, combining the centrifugal plasma separator with the adsorption column, has proved, in our hands, to be a more useful and more convenient method than those previously used for the treatment of severe FH.

Adsorption↗
PubMed1988

Assessment of L-ascorbic acid requirement for prolonged survival in ODS rats and their susceptibility to urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Assessment of L-ascorbic acid requirement for prolonged survival in ODS (genotype: od/od) rats and their susceptibility to urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) were examined. In ODS rats without L-ascorbic acid synthesizing ability, the 50 ppm dietary total ascorbic acid (TAA) was insufficient to survive for 4 weeks, the 250 ppm dietary TAA was sufficient to survive for 36 weeks. In examination of BBN treatment, ODS rats--although showing a lower availability of TAA than the heterozygotes (+/od) and normal (+/+) rats with L-ascorbic acid synthesizing ability--were equally susceptible to bladder carcinogenesis.

Animals↗
PubMed1988

The role of urinary pH and sodium ion concentration in the promotion stage of two-stage carcinogenesis of the rat urinary bladder.

The promoting activities of NaHCO3 and NaCl in two-stage urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated. Male F344 rats were given 0.05% BBN in their drinking water for 4 weeks and then treated with basal diet containing either 3% NaHCO3, 1% NaCl or no added chemical for 32 weeks. NaHCO3 significantly increased the induction of neoplastic and preneoplastic lesions of the urinary bladder, whereas NaCl did not. NaHCO3 produced elevation of urinary pH and urinary Na+ concentration. NaCl increased urinary Na+ concentration without the elevation of urinary pH. In an additional experiment, DNA synthesis in the urinary bladder epithelium was significantly increased in the groups given 3% NaHCO3, 5% sodium L-ascorbate and 1% NaCl. These results confirm that urinary components, increase in urinary pH and Na+ concentration play an important role in the promotion of urinary bladder carcinogenesis in rats.

Animals↗
PubMed1988

Spontaneous tumors in aging (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice.

Spontaneous tumors in untreated (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice used as controls in carcinogenicity tests were recorded. In both sexes, the development of spontaneous tumors was age-related. In 244 male mice, the most common tumors were hyperplastic nodules of the liver, hepatocellular carcinomas, malignant lymphomas/leukemias, lung adenomas, and adenocarcinomas. In 246 female mice, the most common tumors were malignant lymphomas/leukemias, pituitary adenomas, neoplastic nodules of the liver, hepatocellular carcinomas, and lung adenomas. Hepatocellular carcinomas metastasized in 20.3% of the animals with these tumors. Few other tumors except malignant lymphomas and leukemias metastasized. Various tumors of other organs and/or tissues were found at low incidences.

Age Factors↗
PubMed1988

Electrophysiological effects of maprotiline, a tetracyclic antidepressant agent, on isolated cardiac preparations.

We studied the effects of maprotiline, a tetracyclic antidepressant agent, on transmembrane potentials recorded from papillary muscles of guinea pigs and sinoatrial nodes of rabbits, using standard microelectrode techniques. Maprotiline (10-100 microM) produced dose-dependent decreases in the maximum rate of rise (Vmax) and action potential duration in papillary muscles, while the resting potential (Em) was not significantly affected. Maprotiline also shifted the Vmax-Em relation to more negative potentials. The slow action potentials of papillary muscles elicited by high [K+]o were also depressed by the drug application. In sinoatrial node cells, maprotiline (above 10 microM) reduced heart rate, Vmax, and action potential amplitude, and increased the action potential duration at half-amplitude. The slope of the phase 4 depolarization was decelerated by the drug. These results suggest that maprotiline depresses not only the fast inward sodium current but also the slow inward calcium current, and that relatively high concentrations of maprotiline exert an inhibitory effect on the electrical activity of the fast- and slow-response fibers of the hearts.

Action Potentials↗