bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous class switching and B cell hyperactivity increase autoimmunity against intracellular self antigen in Lyn‐deficient mice
Authors: Silver Karlee , Bouriez‐Jones Tiphaine , Crockford Tanya , Ferry Helen , Tang H. Lucy , Cyster Jason G. , Cornall Richard J. 
Published: October 2006

AbstractIgG autoantibodies cause pathology due to their ability to bind self antigens. However, the extent to which the initial B cell activation and isotype switching is antigen‐driven is unclear and it has been widely proposed that intrinsic B cell hyperactivity may be a contributing factor. To explore this issue we generated mice with B cell hyperactivity secondary to deficiency in the src kinase Lyn that also expressed a gene‐targeted anti‐hen egg lysozyme Ig construct (VDJκ) capable of class switching to all isotypes. The B cell hyperactivity caused spontaneous hypersecretion of antibodies and class switching to IgM, IgA, IgG1 and IgG3 isotypes in the absence of self antigen, and this persisted as an autoimmune phenomenon in the presence of intracellularly expressed hen egg lysozyme. Exaggerated class switching was also unaffected by antigen in vitro. These findings show that systemic high‐avidity intracellular self antigens do not induce self tolerance in the face of B cell hyperactivity. Under these circumstances, spontaneous activation of hyperactive B cells leads to isotype switching and the development of high titres of IgG autoantibodies against intracellular proteins.
Grafting of 4‐Hydroxybenzenesulfonic Acid onto Commercially Available Poly(VDF‐co‐HFP) Copolymers for the Preparation of Membranes
Authors: Taguet A. , Ameduri B. , Boutevin B. 
Published: October 2006

AbstractThe grafting of a phenate bearing sulfonate group in solution onto commercially available poly(VDF‐co‐HFP) copolymers, where VDF and HFP stand for vinylidene fluoride and hexafluoropropene, respectively, is presented. This reaction leads to novel fluoropolymers, bearing aryl sulfonic acid side functions, which are fuel cell membrane precursors. A mechanism similar to the grafting of bisphenol onto VDF‐containing copolymers is discussed. First, the sulfonate phenate is modified to give the didecyldimethylammonium bromide sulfonate phenate salt, in order to promote the substitution onto a fluorine atom in VDF unit adjacent to one HFP unit onto a fluorine atom in the copolymer. The substitution of this salt onto the fluorinated copolymer yields low molar percentages of grafted phenate, ranging from 1.8 to 5.1 mol‐%, whereas it reaches values up to 13 mol‐% grafting when the NH2‐CH2‐CH2‐S‐CH2‐CH2‐C6H4‐SO3Na amine is used as the grafting agent. NMR characterization is used to monitor the grafting process. The electrochemical properties of the resulting phenate grafted‐poly(VDF‐co‐HFP) copolymer are studied. The theoretical ion exchange capacities are half that of Nafion®. The proton conductivities are also lower than that of Nafion®, although one conductivity measurement reached a value of 5.1 mS cm–1, showing a non‐negligible conductivity. The water uptake is lower than these noted for a sulfonated amine‐grafted copolymer, and is of the same order as that for Nafion®. Finally, it is shown that these novel materials start to decompose above 200 °C, showing a similar thermostability as that of an amino‐containing aryl sulfonate‐grafted poly(VDF‐co‐HFP) copolymer.
A note on cointegration of health expenditures and income
Authors: Wang Zijun , Rettenmaier Andrew J. 
Published: October 2006

AbstractUtilizing a panel data set of 50 US states, this note investigates nonstationarity and cointegration of health care expenditures and gross state products (GSP). Both the individual state‐based method and the recent panel data method are applied. Allowing for structural breaks in the test, we find that health care expenditures and GSP are both nonstationary. The evidence also suggests that the two series form a cointegrating relationship. The income elasticities of health spending vary over states and became smaller in the 1990s. Copyright © 2006 John Wiley & Sons, Ltd.
Chemical form and distribution of mercury and selenium in canned tuna
Authors: Cappon Chris J. , Smith J. Crispin 
Published: October 2006

AbstractThe content, chemical form and distribution of mercury and selenium were determined for several samples of canned tuna. Samples represented albacore, bluefin, skipjack and yellowfin species, and were packed in either water or vegetable oil. Recently‐processed samples (less than one year old) and much older samples (8–29 years old) were examined. Methylmercury was the predominant mercury form in all samples, comprising 57.4–94.7% of the total mercury content. For these samples, 7.6–44.8% of the total selenium content was present as selenate. There was no apparent effect of packing medium, species or sample age on the methylmercury and selenate percentages. Although the total selenium content exceeded that of total mercury, there was no apparent correlation between the total levels of both elements. Sample age influenced the level of water‐extractable mercury and selenium in canned tuna. For recently canned samples, an average of 27.0% of the total mercury and 55.6% of the total selenium content were water‐extractable. However, for the older samples, the corresponding respective average extractable levels were 46.4 and 48.2%. For both categories, inorganic mercury and selenate were more extractable, on an average percentage basis. In addition, an average of 7.2% of the total mercury content was benzene‐extractable.
Teratogenicity, fetal toxicity and tissue concentration of cadmium administered to female rats during organogenesis
Authors: Barański B. , Stetkiewicz I. , Trzcinka‐ochocka M. , Sitarek K. , Szymczak W. 
Published: October 2006

AbstractCadmium chloride was administered by gavage to pregnant rats from day 7 to day 16 of gestation. Cadmium, when administered at a dose of 40 mg Cd per kg per day, was associated with significant maternal toxicity, placental injury and an increased fetal burden of cadmium. At lower dose levels (2–20 mg Cd per kg per day), fetal development was retarded. Teratogenic effects were not observed and the fetal cadmium concentrations did not differ significantly from the controls, despite the marked cadmium accumulation in the placenta and maternal tissues. The body‐weight gain during gestation of all cadmium‐treated females was reduced and an absolute weight of adrenals in females given cadmium at doses 4 mg kg−1 and higher was significantly increased. The obtained results indicate that cadmium‐induced fetal toxicity is associated with concomitant maternal toxicity and alteration in placental function.
Whole body and liver distribution of inhaled mercury vapor in the mouse: Influence of ethanol and aminotriazole pretreatment
Authors: Khayat Amir , Dencker Lennart 
Published: October 2006

AbstractInhalation of radioactive metallic mercury vapor (203H°) in the mouse resulted in an accumulation of mercury in several organs where no specific uptake was observed after i.v. injection of inorganic mercury (203Hg2+). This was true for the whole respiratory epithelium (including the lung parenchyma), myocardium, brain, retina of the eye, adrenal cortex, corpora lutea of the ovary, epididymis, brown fat and thyroid gland. It is assumed that these organs have a high capacity for oxidizing Hg° to Hg2+, which will then be retained in the tissues. Ethanol and aminotriazole (catalase inhibitors) decreased the concentration in several of these organs, although not in an exactly similar pattern. In the livers of non‐treated animals, most of the inhaled mercury accumulated in the hepatocytes in the periphery of the lobuli (periportal region), close to where the blood vessels enter the liver parenchyma. Treatment with ethanol or aminotriazole increased the liver mercury content, with more or less all the hepatocytes apparently engaged in the oxidation of Hg°.
Influence of alcohol, dithiocarb and (+)‐catechin on the hepatotoxicity and metabolism of vinylidene chloride in rats
Authors: Siegers C.‐P. , Heidbüchel K. , Younes M. 
Published: October 2006

AbstractHepatotoxicity of vinylidene chloride (1,1‐dichloroethylene, VDC) in rats was evidenced by increases of serum enzyme activities of the aminotransferases (GOT, GPT) and sorbitol dehydrogenase (SDH). Simultaneous treatment with ethanol (4.8 g kg−1 p.o.) totally inhibited these hepatotoxic effects, whereas pretreatment with the same ethanol dose 24h prior to VDC had no effect. Dithiocarb or (+)‐catechin (0.2 g kg−1;p.o.), administered simultaneously with VDC, significantly reduced the VDC‐induced increments of serum enzyme activities. Pretreatment with 5% ethanol for 7 days instead of drinking water increased the hepatotoxicity of a single dose of VDC. The combined treatment with VDC (0.125–0.2 g kg−1, twice weekly) and 5% ethanol for 4 weeks led to only small increases of serum enzyme activities as compared with controls treated with VDC alone. However, 60% lethality occurred in the VDC‐ethanol group. Administration of either dithiocarb or (+)‐catechin with VDC totally antagonized the observed lethality. Metabolic studies with VDC in a closed exposure system indicated that simultaneous treatment with ethanol or dithiocarb totally depressed the metabolic removal of VDC, whereas (+)‐catechin had no effect.
Mutagenic effects of aqueous extracts of Symphytum officinale L. and of its alkaloidal fractions
Authors: Fumanowa Mirosława , Guzewska Joanna , Bełdowska Bożena 
Published: October 2006

AbstractSymphytum officinale L. (Boraginaceae) is a medicinal plant widely used in therapy. Its roots, described in the Polish Pharmacopoeia1 as Radix symphyti, are recommended as expectorants, especially for children. Aqueous solutions of three alkaloid fractions obtained from infusions of Symphytum officinale L. root were tested for their antimitotic and mutagenic activity in meristematic cells of the lateral roots of Vicia faba L., var minor. Lasiocarpine, a proven carcinogen, served as a positive control. Mutagenic effects were induced by lasiocarpine, by the alkaloidal fraction I and by diluted infusions from Radix symphyti. Fraction III had only antimitotic effect. The biological activity of the tested solutions is discussed in relation to the relevant literature.
Increased urinary excretion of selenium among workers exposed to elemental mercury vapor
Authors: Alexander J. , Thomassen Y. , Aaseth J. 
Published: October 2006

AbstractThe content of selenium and mercury in urine was measured in 28 male workers exposed to Hg° and in 21 unexposed male controls. The first group excreted significantly more selenium into urine as compared with the control group. No significant correlation between mercury and selenium excretion was found.
Tissue origin of MDH isozymes in blood serum of rats exposed to alkylmercurials
Authors: Brzeźnicka Elżbieta A. , Chmielnicka Jadwiga , Wójcikiewicz‐Herma Łucja 
Published: October 2006

AbstractWistar rats were dosed with Hg at 2.5 mg kg−1 intragastrically as methylmercuric chloride (MeHg) or ethylmercuric chloride (EtHg) on alternate days for 6 weeks. Activities of the mitochondrial (m‐MDH) and cytosol (c‐MDH) isozymes of malate dehydrogenase (MDH; E.C. 1.1.1.37) were studied in the serum, liver and kidneys of rats at 2‐week intervals using agar gel electrophoresis. In order to determine the tissue of origin of the MDH isozymes in rat serum, studies were also made on changes in their activities after poisoning the animals with a hepatotoxic (CCl4) or nephrotoxic(HgCl2) agent. The results indicate that the kidneys are responsible for the increase of the c‐MDH activity in the serum of rats poisoned with EtHg, while in the case of MeHg this increase results from damage initially to the liver and then also to the kidneys.
High‐performance liquid chromatographic analysis of MTX, 7‐OH‐MTX and MTX derivatives: Application to intracellular metabolism in tumor cells (HT 29)
Authors: Durand R. , Fabre G. , Cano J. P. , Catalin J. , Ahmed O. Ait , Just S. 
Published: October 2006

AbstractIn order to study the intracellular metabolism of Methotrexate (MTX) and the cytotoxicity of the antifolates, a specific paired‐ion HPLC method has been developed which permits the simultaneous determination of DAMPA, MTX, 7‐OH‐MTX, MTX‐G1, MTX‐G2 and MTX‐G3. Cells were incubated with 3H‐MTX. The MTX metabolites were extracted, purified on SEP‐PAK cartridges and further analysed by high‐performance liquid chromatography (HPLC). The stationary phase was constituted by a C18 μBondapak and the mobile phase by 5 mM phosphate buffer (pH 7.4) containing 2.5 mM tetrabutylammonium nitrate. The elution was performed with a linear methanol gradient (20–30%). HPLC fractions were collected and radioactivity evaluated by β counting (retention times: DAMPA = 12.93 min; MTX = 18.29 min; 7‐OH‐MTX = 21.13 min; MTX‐G1 = 22.69 min; MTX‐G2 = 26.81 min; MTX‐G3 = 30.61 min). This analytical procedure was applied to separate and characterize multiple forms of MTX polyglutamate derivatives in HT 29, a human adenocarcinoma cell line varying the incubation time (4–18 h) and MTX concentration (0.6‐10.6 μM). The incorporation process seems to be characteristic of a cell line resistant to MTX. The incorporation were very low and after a 4‐h exposure time only 5% of the MTX was converted to polyglutamates. Between 1.6 and 10.6 μM MTX, no difference was observed in the polyglutamization. The defect in the incorporation of the drug and in the metabolization process in vitro could partially explain the failure of the MTX treatment in colorectal cancer.
In vitro and in vivo studies on the potential mutagenicity of alclofenac, dihydroxyalclofenac and alclofenac epoxide
Authors: Mercier M. , Poncelet F. , de Meester C. , McGregor D. B. , Willins M. J. , Léonard A. , Fabry L. 
Published: October 2006

AbstractAlclofenac (A) and two of its metabolites, dihydroxyalclofenac (DHA) and alclofenac epoxide (AE), were tested for their mutagenic potential. Alclofenac and DHA showed no mutagenic, transforming or clastogenic potential in any in vitro experiment. The addition of a supplementary metabolic activation system did not change the response of those two compounds in any test procedures in vitro. AE, an intermediary metabolite between A and DHA, was mutagenic by itself in the Ames test, but in the presence of a liver post‐mitochondrial fraction its activity of Salmonella typhimurium was greatly decreased. Dominant lethal mutations were not induced in male rats given alclofenac, and AE had no effect in the micronucleus test. In human volunteers given alclofenac at therapeutic dose levels, no mutagenic activity was found in the urine and no significant increase in the incidence of structural chromosome aberrations was observed in peripheral blood lymphocytes.
Cadmium‐metallothionein‐induced nephropathy: A morphological and autoradiographic study of cadmium distribution, the development of tubular damage and subsequent cell regeneration
Authors: Murakami M. , Cain K. , Webb M. 
Published: October 2006

AbstractA single intravenous dose of 0.8 mg thionein‐bound cadmium (Cd) per kg body weight, as the isolated (Cd, Zn)‐metallothionein (MT) from rat liver, in rats of the same strain is nephrotoxic, but not lethal. Apical vesiculation in epithelial cells of the renal proximal convoluted tubules is apparent within 1 h of dosing and, by 4 h, is extensive in some of these cells that surround the larger arteries in the cortex. The membranes of these cells appear undamaged. The lesion at first progresses with time; by 24 h, the initially affected cells show extensive necrosis and most proximal convoluted tubular epithelia in other regions of the cortex are hydropically or vacuolarly degenerated. The inner stripe of the outer zone of the medulla and other portions of the nephron (glomerulus, distal tubule and collecting duct), however, appear essentially unaffected. The necrotic changes are maximal at 48 h but, after this time, regeneration begins. By seven days, much of the cell debris has been eliminated and cells of the regenerating or regenerated epithelia are similar in morphology to those of the normal kidney. Electron microscopic autoradiography of kidney sections from rats after administration of 109Cd‐metallothionein of high specific activity shows that Cd is not concentrated in endocytotic vesicles, lysosomes, or any other cellular organelle, even at early times after dosing, but is distributed evenly throughout the epithelial cell. Thus, although Cd‐MT appears to be taken up endocytotically in the kidney tubules, it appears that liberation of Cd from the metalloprotein must occur very early in the reabsorptive process.
Induction of microsomal epoxide hydrolase by tienilic acid in the rat
Authors: Sellman R. , Parkki M. G. 
Published: October 2006

AbstractThe effects of tienilic acid [2,3‐dichloro‐4‐(2‐thienylcarbonyl)phenoxy acetic acid] on drug‐metabolizing enzymes in the rat liver and kidneys were studied. Short‐term treatment for 2 weeks (450 mg per kg per day) increased the activity of microsomal epoxide hydrolase at least two‐fold in both rat liver and kidneys. The effect of tienilic acid on the activity of microsomal epoxide hydrolase in the rat liver correlated with the dose at levels of 20–450 mg per kg per day for 14 days (r = 0.92). Tienilic acid had only marginal effects on cytochrome‐P‐450‐mediated mono‐oxygenases. Tienilic acid caused an approximately two‐fold increase in glucuronide conjugation of 4‐methylumbelliferone in the liver. No increase in the activity of rat hepatic microsomal UDP—glucuronosyltransferase toward O‐aminophenol was detected. According to these results, tienilic acid can be regarded as one of the most specific inducers of microsomal epoxide hydrolase.
Skin‐tumor initiation activity of coal liquids with different boiling‐point ranges
Authors: Mahlum D. Dennis 
Published: October 2006

AbstractHigh‐boiling coal liquids from the solvent‐refined coal‐I and ‐II (SRC‐I, ‐II) processes, respectively, were fractionally distilled. In the case of SRC‐I process solvent (PS), 50°F distillation cuts were obtained between 550 and 850°F, while for the SRC‐II material, the 50°F cuts were only obtained between 700 and 850°F. These cuts, as well as the parent material, were tested for their ability to initiate skin tumors by applying a single dose (25 mg) to the shaved backs of Charles River female CD‐1 mice. After 2 weeks, the mice received twice weekly applications of 5 μg of the promoter, phorbol myristate acetate. Only a few tumors were found for SRC‐I fractions boiling below 700°F; tumor‐initiating activity increased as the boiling point increased. A similar increase in response with increasing boiling point was seen for the SRC‐II cuts. The initiating activities for the parent materials were similar to those observed for their respective 800 to 850°F cuts.
Acute toxicity study of 1,3,3,5,5‐pentaziridino‐1‐thia‐2,4,6‐triaza‐3,5‐diphosphorine‐1‐oxide (a new antitumor agent with an inorganic ring) in mice, rats and dogs
Authors: Nakano Shigeki , Yamashita Kazumasa , Kirihara Yoshinobu , Kuwata Masahiko , Morita Ken'ichi 
Published: October 2006

AbstractIn order to study the safety of 1,3,3,5,5‐pentaziridino‐1‐thia‐2,4,6‐triaza‐3,5‐diphosphorme‐1‐oxide(SOAz), a new antitumor agent, acute toxicity studies by intravenous administration were performed in ddY mice, Wistar rats and beagle dogs. The LD50 values in rodents were 325 mg kg−1 for male mice, 450 mg kg−1 for female mice, 100 mg kg−1 for male rats and 82 mg kg−1 for female rats. In dogs, the LD50 values were 12 mg kg−1 for males and 18 mg/kg−1 for females. The dosed animals showed diarrhoea and decreased movement in the three species, and emaciation and loss of body weight in mice and rats. Dogs also showed signs of pneumonia. Histopathological examination revealed bone marrow suppression, atrophy of lymphoid organs and testes, and damage to the digestive tract mucosa in the three species. The main causes of death from single‐dose administration were bone marrow aplasia and atrophy of lymphoid tissue in all species, together with gastro‐intestinal ulceration in rats and dogs, and infection in mice and dogs.
The subchronic oral toxicity of polyphenylene sulfide
Authors: Thomas W. C. , Kirwin C. J. , Wazeter F. X. , Jessup D. C. 
Published: October 2006

AbstractPolyphenylene sulfide was offered to Charles River CD® rats for 6 months in the diet at concentrations of 0.00, 0.50, 2.75 and 5.00% (w/w). In this study, animals of both sexes consumed polyphenylene sulfide for 6 months without exhibiting compound‐related effects. Parameters studied were: body weight, hematology, clinical chemistry, urinalysis, organ weights, gross pathology and histopathology.
Relaxation of rabbit aorta by chlordimeform
Authors: Robinson Casey P. 
Published: October 2006

AbstractChlordimeform N′‐(4‐choro‐O‐tolyl)‐N, N‐dimethyl‐formamidine; CDF), an acaracide‐insecticide, relaxed helically cut strips of rabbit thoracic aorta and deadventitiated aorta strips. Relaxations by CDF of aorta strips contracted by 5 × 10−7M prostaglandin F2α were not altered by the antimuscarinic agent atropine (10−5M), the beta‐adrenergic antagonist propranolol (10−5M), the histamine H2 antagonist cimetidine (2 × 10−4M), the dopamine antagonist haloperidol (10−5M) or the Na+‐K+‐ATPase inhibitor ouabain (5 × 10−6M). CDF further relaxed deadventitiated strips contracted by 10−6M NE or 40 mM potassium and then partially relaxed by 10−5M verapamil. CDF (10−5M) potentiated contractions caused by the addition of calcium to potassium depolarized strips in zero calcium media, but higher concentrations reduced calcium‐induced contractions. The highest CDF concentration (10−2M) not only prevented tension increase on calcium addition, but also progressively decreased tension to below baseline levels. The addition of 10−2M CDF to aorta strips not contracted by a vasoactive agent decreased resting tension. This relaxation was usually maximal at 10−3M and less at 10−2M. Thus, CDF relaxes vascular smooth muscle, not by antagonism at the usual vascular relaxant receptors, but by interference with calcium utilization.
Developmental toxicity following oral administration of a high‐boiling coal liquid to pregnant rats
Authors: Hackett P. L. , Rommereim D. N. , Sikov M. R. 
Published: October 2006

AbstractHeavy distillate (HD), the highest‐boiling coal liquid from the solvent‐refined coal‐II process (SRC‐II), was administered by intragastric (IG) intubation to pregnant rats. Five dose levels of HD (0.09, 0.14, 0.18, 0.36 and 0.74 g kg−1), were given daily from 12 to 16 days of gestation and the rats were killed at 20 days of gestation. Maternal body weights and weights of the liver, kidneys, spleen, adrenals, thymus, ovaries and the gravid uterus were obtained. Gravid uteri were evaluated for prenatal mortality. Live fetuses were examined for malformations and weighed; fetal lungs were excised and weighed. Maternal (extragestational) weight gains and thymic weights diminished in all groups that received the SRC material. Adrenal weights were increased in all treated animals, except for those in the lowest‐dose group (0.9 g kg−1). There was significant maternal mortality at 0.74 g kg−1 and increased intrauterine mortality at doses of 0.37 and 0.74 g kg−1. Placental weight was depressed, and the incidence of fetal anomalies was increased at 0.14 g kg−1 and all higher dose levels.