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Biomedical subjects

H Kosaka

Publications and source records attributed to H Kosaka.

At least 163 records · Page 9Linked to original sources
PubMed1990

Marked nitrosation by stimulation with lipopolysaccharide in ascorbic acid-deficient rats.

Marked formation of N-nitrosothioproline (N-nitrosothiazolidine-4-carboxylic acid) by stimulation with Escherichia coli lipopolysaccharide (LPS) was demonstrated in ascorbic acid-deficient mutant rats (osteogenic disorder syndrome rats; ODS rats) unable to synthesize ascorbic acid. The amounts of urinary nitrate and N-nitrosothioproline excretion after thioproline administration was measured in ODS rats with and without ascorbic acid supplement before and after the injection of LPS. LPS caused marked increase of urinary nitrate excretion in both groups. Urinary N-nitrosothioproline excretion increased 6-fold after LPS injection in ODS rats not supplied with ascorbic acid, but supplement with ascorbic acid markedly decreased the excretion of N-nitrosothioproline.

Adrenal Glands↗
PubMed1990

T cell clones are killed by a thymic stromal cell monolayer following stimulation of T cell receptor with antigen and/or H-2 molecules on the monolayer.

A thymic stromal cell clone, MRL104.8a, expressed class I and class II H-2k antigens after exposure to gamma-interferon (gamma-IFN) and produced thymic stroma-derived T cell growth factor (TSTGF) irrespective of gamma-IFN exposure. Culturing the keyhole limpet hemocyanin (KLH)-specific, I-Ek-restricted 9-16 helper T cell (Th) clone on an Ia (I-Ak and I-Ek)-expressing MRL 104.8a monolayer induced potent proliferation of the 9-16 cells by virtue of the TSTGF produced by the monolayer. In contrast, the addition of KLH to cultures resulted in lethal growth inhibition of the 9-16 Th clone. Such a phenomenon was also observed for various Th as well as cytotoxic T lymphocyte (CTL) clones, and the following were revealed: (i) the growth of the ovalbumin (OVA)-or bovine thyroglobulin (BTg)-specific Th clone on the la-expressing MRL 104.8a monolayer was also inhibited by addition of the relevant antigen. The fact that these Th clones required antigen-presenting cells (APC) capable of processing antigen for the recognition of the respective target antigen suggested the potential of MRL 104.8a cells for antigen-processing; (ii) the lethal growth inhibition of KLH-specific, I-Ak (23-1-8)- or I-Ek (9-16)-restricted Th clone was prevented selectively by anti-I-Ak or anti-I-Ek antibody respectively; (iii) the I-Ek-alloreactive Th clone (2-13) was supported for its growth on a gamma-IFN-unexposed MRL 104.8a monolayer, whereas this clone was killed on an I-Ek-expressing monolayer; and (iv) when I-Ak-reactive CTL clones were cultured on an Ia- or Ia+ monolayer, CTL clones failed to exhibit cytotoxic effect on either the Ia- or the Ia+ monolayer, but were conversely killed by the Ia+ monolayer. Its killing was also prevented by an antibody which inhibits the recognition of Ia antigen on the monolayer by CTL clones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Genotoxicity of synthetic dyes in umu test using Salmonella typhimurium TA1535/pSK1002 (1). Results of examination for acid dyes, direct dyes, disperse dyes and reactive dyes].

The umu test system is a newly developed method to evaluate genotoxicities of a wide variety of environmental carcinogens and mutagens (Oda et al., 1985; Nakamura et al., 1987). In the present study, SOS-inducing activity of 142 synthetic dyes was investigated by the umu test using Salmonella typhimurium (TA1535/pSK1002) under the condition of absence and presence of rat liver microsomal fraction. The samples showing a beta-galactosidase activity of more than 1.5 fold over the background level were reexamined and the dose-response curves were prepared at various doses. Then, the samples showing beta-galactosidase activity of more than 1.5-fold of the background level were defined as genotoxic. Among the synthetic dyes examined, 11 compounds induced umu gene expression. The potent genotoxic compounds without metabolic activation were Acid Black 26, Acid Black 50, Acid Brown 2, Disperse Red 73, Disperse Red 145, Disperse Red 157, Disperse Violet 52, Reactive Red 110, Reactive Yellow 13 and Reactive Yellow 75, and in the presence of S9, Reactive Blue 147 was judged to be genotoxic. An evident dose-response relationship was observed between the doses of the dye and umu-gene expression in these 11 dyes.

Coloring Agents↗
PubMed1990

[Genotoxicity of synthetic dyes in the umu test using Salmonella typhimurium TA1535/pSK1002 (II). Results of examination of basic dyes].

In the present study, SOS-inducing activity of 76 basic dyes was investigated by umu test using Salmonella typhimurium TA1535/pSK1002 under the condition of absence and presence of rat liver microsomal fraction. The test was carried out with five doses of basic dyes (400, 120, 40, 12, and 4 micrograms/ml). The samples showing beta-galactosidase activity more than 1.5-fold over the background level were reexamined and the dose-response curves were prepared at various doses. Thereafter, samples showing beta-galactosidase activity unit more than 1.5-fold of the background level were defined as genotoxic. Among the basic dyes examined, 13 compounds induced umu gene expression. The potent genotoxic compounds without metabolic activation were Blue 40, Blue 47, Brown 14, Orange 30, Red 24, Violet 30, Violet 31, Yellow 13(h), Yellow 19, Yellow 25, Yellow 67, and Yellow 73 and in the presence of S9, Orange 47 was judged as genotoxic in addition to the aforementioned dyes. An evident dose-response relationship between the doses of the dye and umu gene expression was observed in these 13 dyes.

Coloring Agents↗
PubMed1989

Thymic stroma-derived T cell growth factor (TSTGF). IV. Capacity of TSTGF to promote the growth of L3T4- Lyt-2- thymocytes by synergy with phorbol myristate acetate or various IL.

The present study investigates the role of thymic stroma-derived T cell growth factor (TSTGF) in promoting the growth of L3T4- Lyt2- (double-negative) thymocytes. Partially purified TSTGF samples were prepared from the culture supernatant of a newly established thymic stromal cell line, MRL104.8a. The TSTGF alone induced only marginal proliferation of double-negative thymocytes, whereas this factor exerted a potent growth-promoting effect on these cells in combination with PMA. Because such an enhanced proliferation was not inhibited by anti-IL-4 or anti-IL-2R antibody, this was not due to the stimulation of an autocrine mechanism involving the production and utilization of IL-4 or IL-2. In scrutinizing PMA-equivalent physiologic substance(s), IL-1 was revealed to be capable of replacing the role of PMA in the above co-stimulation cultures and including enhanced proliferation of double-negative thymocytes in combination with TSTGF. Although TSTGF plus IL-2 or IL-4 also exhibited an appreciable or moderate synergistic effect on the growth of double-negative thymocytes, its magnitude was weaker compared with that obtained by TSTGF plus IL-1. More important, the strikingly enhanced proliferation was induced in the combinations of TSTGF, IL-1, and IL-2 or IL-4 under conditions in which the proliferation induced by IL-1 plus IL-4 or IL-1 plus IL-2 was marginal or slight. Furthermore, such strongly enhanced proliferation was also observed in the double-negative thymocyte population which was additionally depleted of T3+ cells (namely, the L3T4- Lyt-2- T3- or dull population). These results indicate the crucial role of TSTGF in the proliferation of immature thymocytes by synergy with various cytokines.

Adjuvants, Immunologic↗
PubMed1989

Capacities of a newly established thymic stromal cell clone to express Ia antigens and to produce interleukin-6, colony-stimulating factor, and thymic stroma-derived T-cell growth factor.

Thymic stromal cell lines, termed MRL104 and MRL28, have been isolated from long-term liquid cultures of thymic stromal cells from MRL/l mice. The capacities of these parental lines and derived clones to express Ia antigens and to produce cytokines involved in T-cell proliferation and/or differentiation were investigated. Parental lines and their clones did not exhibit a typical fibroblastic, macrophage-like, or epithelial appearance in electron as well as phase-contrast micrographs. These thymic stromal cells seemed to differ from established fibroblast lines in that these thymic stromal cells expressed Ia antigens after exposure to interferon-gamma (IFN-gamma), whereas fibroblast lines did not. They also appeared to differ from macrophage cell lines in that they lacked the expression of Mac-1 antigens on their cell surface and produced no detectable level of interleukin-1 (IL1) before or even after exposure to lipopolysaccharide. When these parental lines and its clones were tested for their ability to produce various types of cytokines, it was revealed that they were capable of producing colony-stimulating factor (CSF), IL6, and thymic stroma-derived T cell growth factor (TSTGF), which was recently described, but were unable to generate other lymphokines and IFNs. Thus these cell lines and clones represent unique features in that they have potentials to express Ia antigens and to produce CSF, IL6, and TSTGF. The biological significance for the expression of these features is discussed in the context of intrathymic T-cell maturation and T-cell repertoire selection.

Animals↗
PubMed1989

The interaction between nitrogen oxides and hemoglobin and endothelium-derived relaxing factor.

Among nitrogen oxides, NO and NO2 are free radicals and show a variety of biological effects. NO2 is a strongly oxidizing toxicant, although NO, not oxidizing as NO2, is toxic in that it interacts with hemoglobin to form nitrosyl- and methemoglobin. Nitrosylhemoglobin shows a characteristic electron spin resonance (ESR) signal due to an odd electron localized on the nitrogen atom of NO and reacts with oxygen to yield nitrate and methemoglobin, which is rapidly reduced by methemoglobin reductase in red cells. NO was found to inhibit the reductase activity. Part of NO inhaled in the body is oxidized by oxygen to NO2, which easily dissolves in water and converts to nitrite and nitrate. The nitrite oxidizes oxyhemoglobin autocatalytically after a lag. The mechanism of the oxidation, particularly the involvement of superoxide, was controversial. The stoichiometry of the reaction has now been established using nitrate ion electrode and a methemoglobin free radical was detected by ESR during the oxidation. Complete inhibition of the autocatalysis by aniline or aminopyrine suggests that the radical catalyzes conversion of nitrite to NO2, which oxidizes oxyhemoglobin. Recently NO was shown to be one of endothelium-derived relaxing factors and the relaxation induced by the factor was inhibited by hemoglobin and potentiated by superoxide dismutase.

Free Radicals↗
PubMed1989

Model for clonal elimination in the thymus.

A thymic stromal cell clone, MRL104.8a, expresses class I as well as class II H-2k antigens after exposure to gamma-interferon. This clone also produces thymic stroma-derived T-cell growth factor (TSTGF), which is distinct from other known interleukins and is capable of promoting the growth of various antigen-specific helper T cell (Th) clones without requiring a specific antigen or interleukin 2. When the keyhole limpet hemocyanin (KLH)-specific, I-Ek-restricted Th clone 9-16 was cultured on an Ia (I-Ak and I-Ek)-expressing MRL104.8a monolayer, potent proliferation of the 9-16 cells was induced by TSTGF produced by the monolayer. In contrast, the addition of KLH resulted in lethal growth inhibition of Th clone 9-16 cells. Another Th clone that is KLH-specific but I-Ab-restricted was capable of proliferating on the Iak-expressing MRL104.8a monolayer whether or not KLH was present. More importantly, death of Th clone 9-16 cells cultured on a MRL104.8a monolayer in the presence of KLH was almost completely prevented by the addition of anti-I-Ek or anti-CD3 monoclonal antibodies, which are capable of blocking antigen recognition by the T-cell receptor. However, when Th clone 9-16 cells were cultured in the presence of KLH but on a monolayer of MRL28.8a cells, another thymic stromal clone that expresses a comparable amount of I-Ek antigen but produces a marginal amount of TSTGF, cells did not die; a lethal effect was induced by adding TSTGF. These results indicate that the TSTGF-producing and Ia-expressing thymic stromal cells induce the continuous proliferation or selective elimination of each T-cell clone, depending on whether the T-cell receptor is stimulated by the relevant antigen associated with Ia molecules expressed on the stromal cell surface.

Animals↗
PubMed1989

Nitrosation by stimulated macrophages. Inhibitors, enhancers and substrates.

Macrophages and their immortalized cell lines can be activated to form nitrite and nitrate via oxidation of arginine and this is accompanied by the formation of N-nitroso compounds. The mechanism of nitrosamine formation has been investigated through the use of compounds which are known either to inhibit or enhance acid-catalyzed nitrosation. The range of nitrogen acceptors has been expanded to include ureas as well as amines of varying pKa and structure. The results are consistent with a mechanism in which NO is oxidized to N2O3 and N2O4, which are capable of nitrosating amines, but not ureas or amides, at neutral pH. This is in agreement with a recent observation that macrophage cell-free extracts can oxidize arginine to NO. The effect of ascorbic acid on intact activated macrophages is complex since nitrite formation is enhanced over a very wide range of ascorbate concentrations (5-500 microM) while nitrosation is inhibited at ascorbate concentrations greater than 50 microM.

Arginine↗
PubMed1988

[Assessment of occupational exposures to industrial hazardous substances. II. Interday fluctuations of the daily exposure averages among workers exposed to lead].

An assessment of the employee's exposures to industrial hazardous substances using the proposed method described earlier was conducted on 49 workers exposed to lead. As it is assumed that the daily exposure averages are lognormally distributed, geometric standard deviation (sigma g) representing true interday fluctuations of the daily exposures was estimated by personal exposure measurements of every worker for two consecutive days. The estimates (Sg) ranged from 1.00 to 5.35 with a median of 1.4 and a 90% upper limit of 2.4. According to a classification scheme in the proposed method, exposure levels (I to III) were calculated using sigma g of 1.4 and 2.4. An exposure class based on a single day measurement was evaluated and compared to that based on measurements for two consecutive days. As a result, the decision of the exposure levels and classes from only one day monitoring could be made by using both sigma g of 1.4 and 2.4, representing ordinary and high interday fluctuations, respectively. More accurate estimate of geometric standard deviation of interday fluctuations by exposure monitorings would provide a more reliable assessment of the worker's long-term exposure situation.

Data Interpretation, Statistical↗
PubMed1988

Thymic stroma-derived T cell growth factor: its role in the growth of immature thymocytes and T cell repertoire selection.

A newly established thymic stromal cell clone, MRL104.8a exhibited capacities to express Ia antigens and to support the growth of antigen-specific, interleukin-2 (IL-2)-dependent helper T cell (Th) clones without requirement of antigen and exogenous IL-2. Such growth was substituted by a factor produced into cultures by the MRL104.8a clone. This substance designated as thymic stroma-derived T cell growth factor (TSTGF) was demonstrated to be the protein that has an apparent molecular weight of about 25,000 and a pI of 6.0 and to be distinct from the previously described interleukins and cytokines. While the capacity of TSTGF to promote T cell proliferation was initially found by using various Th clones, further studies have demonstrated its capability of supporting the growth of immature (L3T4- Lyt-2-) thymocytes. TSTGF alone failed to function for the proliferation of double-negative thymocytes, whereas this novel growth factor was capable of inducing the proliferation of immature thymocytes by synergy with IL-1. Such growth promotion was further enhanced by the addition of IL-2 or IL-4 to cultures. The data were also presented that TSTGF could contribute to the clonal elimination in the thymus. The growth of a Th clone, 9-16, was supported on the TSTGF-producing and Ia-expressing MRL104.8a monolayer in the absence of the antigen against which this Th clone is directed. In contrast, the presence of the relevant antigen in the MRL104.8a culture elicited the lethal growth-inhibition of Th clone cells. Taken collectively, the results provide strong support for the proposition that TSTGF may play an essential role in the intrathymic T cell development in the context of T cell growth promotion and T cell repertoire selection.

Animals↗
PubMed1987

Cyclosporin A inhibits late steps of T lymphocyte activation after transmembrane signaling.

The in vitro stimulation of murine splenic T lymphocytes with concanavalin A (Con A) produced interleukin 2 (IL2). The addition of cyclosporin A (CsA) to the culture resulted in complete inhibition of IL2 production. The Con A stimulation of T lymphocytes induced the breakdown of phosphatidylinositol into inositol trisphosphate and diacylglycerol, each of which could function as the second messengers in the subsequent signal transduction pathway. CsA did not inhibit the production of inositol (poly)phosphates. Further, CsA did not affect Ca2+-calmodulin functions; a) the redistribution of various cytoskeletal proteins as well as Con A-receptor aggregation, and b) the cytosolic Ca2+-calmodulin-dependent enzyme activities. Moreover, the activity of protein kinase C, which has been accepted to be the target of diacylglycerol, was not influenced in the presence of CsA. While the above steps of signal transduction are bypassed by synergy between calcium ionophore and phorbol ester, T lymphocyte activation which was induced by such stimuli was completely inhibited by CsA. These results indicate that CsA does not influence early steps of T lymphocyte activation as bypassed by calcium ionophore and phorbol ester, but rather inhibits later step(s) subsequent to the activation of protein kinase C and Ca2+-calmodulin.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Mechanism of autocatalytic oxidation of oxyhemoglobin by nitrite.

Oxidation of oxyhemoglobin by nitrite is characterized by the presence of a lag phase followed by autocatalysis. The stoichiometry of the overall reaction is described by the following equation: 4HbO2 + 4NO2- + 4H+ = 4Hb+ + 4NO3- + O2 + 2H2O (Hb denotes hemoglobin monomer). During the oxidation, we detected a free radical at g = 2.005, which is very similar to the methemoglobin free radical generated by the reaction with hydrogen peroxide. Nitrosylhemoglobin was not detected. The oxidation was delayed by the addition of KCN or catalase, but was not modified by superoxide dismutase in phosphate buffer. In bistris buffer, however, superoxide dimutase markedly prolonged the lag phase. The results suggest that during the oxidation, the methemoglobin peroxide compound is generated and converts nitrite into nitrogen dioxide by its peroxidatic activity. Nitrogen dioxide oxidizes oxyhemoglobin to methemoglobin and nitrite, yielding the autocatalytic phase.

Electron Spin Resonance Spectroscopy↗
PubMed1987

Induction of SOS functions in Escherichia coli and biosynthesis of nitrosamine in rabbits by nitrogen dioxide.

Nitrogen dioxide induced SOS functions in Salmonella typhimurium and Escherichia coli K-12 and was mutagenic in Escherichia coli WP2. When a rabbit was administered aminopyrine intravenously and administered nitrogen dioxide by inhalation, N-nitrosodimethylamine was detected in its blood. Analysis was conducted with 15N-nitrosodimethylamine as an internal standard by a combination of capillary gas chromatography and mass spectrometry. Accompanying administration of cystamine increased the blood concentration of N-nitrosodimethylamine in the rabbit, suggesting inhibition of its metabolism. Concurrent sulfur trioxide inhalation increased N-nitrosodimethylamine formation in the rabbit.

Aminopyrine↗
PubMed1987

[An interview survey on health care service in small-sized manufacturers in a city of Osaka Prefecture].

An interview survey on the health care service for workers employed in small-sized enterprises was conducted in a city of Osaka Prefecture. Items surveyed were: 1) number of full-time and part-time employees by age (less than 39, 40-60, and more than 60 yr) and sex, 2) materials and production process, 3) periodic examinations for general health status and occupational diseases, and others. Of the 526 enterprises interviewed, 459 manufacturers with less than 50 employees were analyzed. The results can be summarized as follows: 1. Of the 459 manufacturers, 72.4% were those with less than 10 workers (the mean number of employees: 8.4). The major type of manufacture was electric parts processing industry. 2. The period health examination has been carried out in 372 enterprises (81.0%). The smaller the size of the company, the lower was the rate of the periodic health examination. 3. In 77.4% of the 372 enterprises, only chest X-ray was an item for the periodic health examination, which was usually carried out at the public health center of the community. 4. The number of enterprises conducting the periodic health examination designated by the Industrial Safety and Health Law (1972) was only 49 (10.7%). 5. Fourteen enterprises (3.1%) have carried out periodic examination for occupational diseases. 6. The periodic examination for degenerative diseases such as hypertension, diabetes mellitus, and other cardiovascular diseases was carried out in 57 enterprises (12.4%). The larger the size of the company, the higher was the rate in which such examination was conducted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Inhibition by amines indicates involvement of nitrogen dioxide in autocatalytic oxidation of oxyhemoglobin by nitrite.

Oxidation of oxyhemoglobin by nitrite is characterized by a lag period followed by an autocatalytic phase. The oxidation can be inhibited by the addition of morpholine, piperidine, triethanolamine or triethylamine (6 mM each). These amines are known to react with nitrogen dioxide to yield nitrosamine. Unexpectedly, aniline or aminopyrine (120 microM each) markedly inhibited the oxidation. These compounds, but not the other amines given above, inhibited the peroxide compound formation from methemoglobin and hydrogen peroxide. The results establish that, during the oxidation, the peroxide compound is generated and converts nitrite into nitrogen dioxide by its peroxidatic activity, resulting in an autocatalytic phase.

Amines↗