cytogenetic and germ cell effects of phosphine inhalation by rodents: II. subacute exposures to rats and mice

Phosphine (PH₃) is a highly toxic grain fumigant to which there is significant human workplace exposure. To determine the in vivo cytogenetic effects of inhalation of PH₃, male F344/N rats and B6C3F1 mice were exposed to target concentrations of 0, 1.25, 2.5, or 5 ppm PH₃ for 6 hr/day for 9 days over an 11 -day period. Approximately 20 hr after the termination of exposures, blood was removed from the mice and rats by cardiac puncture and the lymphocytes cultured for analyses of sister chromatid exchanges and chromosome aberrations in rats and mice, and micronuclei (MN) in cytochalasin B-induced binucleated lymphocytes from mice. In addition, bone marrow (rats) and peripheral blood (mice) smears were made for the analysis of MN in polychromatic and normochromatic erythrocytes. No significant increase in any of the cytogenetic endpoints was found at any of the concentrations examined. These results indicate that concentrations of PH₃ up to 5 ppm are not genotoxic to rodents when administered by inhalation for 9 days during an 11 -day period as measured by several cytogenetic assays. To evaluate the effects of PH₃ on male germ cells, a dominant lethal test was conducted in male mice exposed to 5 ppm PH₃ for 10 days over a 12-day period and mated to groups of untreated females (2 females/male) on each of 6 consecutive 4-day mating intervals. None of the 6 groups of females exhibited a significant increase in percent resorptions. These results indicate that exposure to 5 ppm PH₃ by inhalation does not induce dominant lethality in male mouse germ cells at steps in spermatogenesis ranging from late differentiating spermatogonia/early primary spermatocytes through mature sperm. © 1994 Wiley-Liss, Inc.     

Chronic ingestion of clastogens by mice and the frequency of chromosome aberrations

Environmental exposure to mutagens is believed to play a significant role in human carcinogenesis. Determination of the in vivo effects of a single mutagen is best done in laboratory animals because humans are exposed to a variety of mutagens both in their diet and in the rest of their environment. In this study, C57BL/6N female mice were used to analyze the effect on chromosomes of chronic ingestion of a mutagen dissolved in drinking water. Cyclophosphamide (CP) or urethane (ethyl carbamate, EC) were dissolved in sterile drinking water at concentrations of 0, 32, 64, and 96 ppm or 0, 5,000, 10,000, and 15,000 ppm, respectively. All exposures began at 8 weeks of age and continued through the 20th week unless terminated earlier due to toxicity. Body weights and water consumption were measured weekly. Blood and bone marrow were taken from approximately five mice per exposure group at 4, 8, and 12 weeks from the start of exposure. All mice remaining after 12 weeks received drinking water without any carcinogen for an additional 6 weeks to determine if induced aberrations persisted. Chromosome translocations, measured by painting, were not induced in blood or bone marrow cells at any time point for either chemical. However, both carcinogens induced significant increases in micronucleated normochromatic erythrocytes, indicating that the carcinogens reached the tissues examined in these experiments. These results indicate that chronic exposure of mice to chemical carcinogens induces chromosome breakage measurable by micronuclei. However, the breakage and reunion necessary to see chromosome exchanges such as translocations were not observed in this study. Environ. Mol. Mutagen. 32:139–147, 1998 © 1998 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Group transfer initiated polymerization of methyl methacrylate catalyzed by [((C6H5)3P)2N]+HF

Experments are reported on the group transfer polymerization of methyl methacrylate using a new bifluoride salt, bis(triphenylphosphoranylidene)ammonium hydrogendifluoride

1 Commonly abbreviated as PPN bifluoride (PPN HF₂).

[((C₆H₅)₃P)₂N]⁺HF, as catalyst. Good molecular weight control was observed although a small deviation from the expected value was found. Side reactions of catalyst with initiator, and termination (cyclization) of the active centres at low monomer concentrations were investigated. The similarities between this method and classical anionic polymerization are discussed.     

Influence of chemical structure on glass transition temperatures of poly(propylene terephthalate) and poly(propylene isophthalate)

Poly(propylene terephthalate)

1 Systematic IUPAC name: poly(oxypropyleneoxyterephthaloyl).

(PPTP) and poly(propylene isophthalate)

2 Systematic IUPAC name: poly(oxypropyleneoxyisophthaloyl).

(PPIP) were prepared by melt polycondensation. Different fractions with number-average molar masses in the range 5 000 ? 20 000 g·mol^?1 were obtained and their respective glass transition temperatures (T_g) determined by calorimetry. The solubility parameters of the polymers were obtained by viscosity measurements in different solvents and were found to be 9,4 and 9,5 cal^1/2·cm^?3/2 (19,2·10³ and 19,4·10³ J^1/2·m^?3/2) for PPIP and PPTP, respectively. The glass transition temperatures were compared with those reported for analogous polyesters and it was shown that intramolecular interactions highly influence the T_g of these polyesters, whereas the effect of intermolecular interactions seems to be less important.     

Copolymerization of 5-norbornen-2-yl acetate with cycloalkenes by the metathesis catalyst WCl6/(CH3)4Sn

Ring-opening metathesis copolymerization of 5-norbornen-2-yl

1 System. name: bicyclo[2.2.1]hept-5-en-2-yl.

acetate (NBEAc; 80% endo) with cyclooctene (COE) and norbornene

2 System. name: bicyclo[2.2.1]hept-2-ene.

(NBE) was studied using WCl₆/(CH₃)₄Sn as catalytic system. The copolymerization parameters (r₁ = r₂ = 1 for the NBEAc/NBE system and r₁ = 1/r₂ = 132 for the NBEAc/COE system) show that the reactivity of the monomers is not affected by the presence of an ester substituent but that it depends on the structure of the hydrocarbon cycle. Thus the well known inhibition effect of the ester group may be concluded not to lie in the propagation step of the catalytic cycle.     

The balance between intrahepatic IL-17+ T cells and Foxp3+ regulatory T cells plays an important role in HBV-related end-stage liver disease

Background

The aqueous extract of a Brazilian palm-tree fruit - the babassu - (BAE) exerts a clear immunostimulative activity in vivo. In the present work, the possibility that BAE can promote Th1 immune responses in mice of a Th2 immune response-prone strain - the BALB/c was investigated. BAE itself, and preparations consisting of Leishmania amazonensis promastigote extract (LE), adsorbed or not to Al(OH)₃, and in the presence or not of BAE, were used as immunogens. LE and Al(OH)₃ have been shown to preferentially elicit Th2 immune responses.

Results

The addition of BAE to LE-containing immunogenic preparations, adsorbed or not to Al(OH)₃, clearly promoted the in vitro production of interferon γ (IFN-γ), a major Th1-dependent cytokine, and not of interleukin (IL-)4 (a Th2-dependent cytokine), by LE-stimulated splenocytes of immunized BALB/c mice. It also promoted the in vivo formation of IgG2a anti-LE antibodies. However, immunization with LE by itself led to an increased production of IL-4 by LE-stimulated splenocytes, and this production, albeit not enhanced, was not reduced by the addition of BAE to the immunogen. On the other hand, the IL-4 production by LE-stimulated splenocytes was significantly lower in mice immunized with a preparation containing Al(OH)₃-adsorbed LE and BAE than in mice immunized with the control preparation of Al(OH)₃-adsorbed LE without BAE. Moreover, an increased production of IFN-γ, and not of IL-4, was observed in the culture supernatants of splenocytes, from BAE-immunized mice, which were in vitro stimulated with BAE or which received no specific in vitro stimulus. No differences in IL-10 (an immunoregulatory cytokine) levels in the supernatants of splenocytes from mice that were injected with BAE, in relation to splenocytes from control mice, were observed. The spontaneous ex vivo production of NO by splenocytes of mice that had been injected with BAE was significantly higher than the production of NO by splenocytes of control mice.

Conclusions

Based on the results described above, BAE, or biologically active molecules purified from it, should be further investigated as a possible adjuvant, in association or not with aluminium compounds, for the preferential induction of Th1-dependent immune responses against different antigens in distinct murine strains and animal species.     

Copolymerization of propene with 1-alkenes using a MgCl2/TiCl4 catalyst

Copolymerization of propylene

1 System name: propene.

and 1-alkenes (1-octene, 1-decene, 1-dodecene, 1-tetradecene, 1-hexadecene) were studied with the catalyst system MgCl₂/TiCl₄-Al(i-Bu)₃. It was found that the polymerization productivity and the consumption rate of propylene are improved significantly in the presence of the comonomer. The total productivity of propylene/1-alkene copolymerizations decreases as follows: 1-octene > 1-decene > 1-dodecene > 1-hexadecene > 1-tetradecene. The reactivity ratios were estimated from the copolymerization results.     

Coordination polymerization of lactides, 2. Microstructure determination of poly[(L,L-lactide)-co-(ε-caprolactone)] with 13C nuclear magnetic resonance spectroscopy

A detailed analysis of the structure of poly[(L ,L -lactide)-co-(ε-caprolactone)]

1 IUPAC-preferred name is dilactide:

was performed by means of high resolution ¹³C NMR (75 MHz) spectroscopy. The polyesters were obtained using various comonomer ratios and initiators aluminium tris(acetylacetonate) or the system Al(C₂H₅)₃ + Zn(C₂H₅)₂ + H₂O. Signals in spectra were assigned to appropriate structural sequences. Two types of chain structure containing different sequences and depending on the initiator used in copolymerization were found.     

Synthesis and thermal properties of side-chain liquid-crystalline poly(glycidyl ethers) with racemic and chiral backbone

Oxiranes bearing a 4-cyanobiphenyl-4′-oxy mesogenic group with spacers of different length have been synthesized from glycidyl p-toluenesulfonate or epichlorohydrin (racemic or optically active). These monomers were polymerized with anionic initiators (CsOH, tBuOK

1 tBu: tert-butyl, Et: ethyl.

) or a chelate initiator (AlEt₃/H₂O/acetylacetone ). A transfer of chirality from the polymer backbone to the mesophase is observed for polyethers with a short spacer. A cholesteric phase is observed for the optically active polymer while the racemic polymer is nematic. Increasing the length of the spacer leads to a smectic mesophase. However, in that case, the effect of the chiral centre of the polymer backbone on the mesomorphous properties is not detected.     

Morphology and properties of polybutadiene- and polyether-polyurethane zwitterionomers

Two series of polyurethane zwitterionomers based on 4,4′-methylene-di(phenyl isocyanate) (MDI), N-methyl diethanolamine (MDEA)

1 Systematic IUPAC name: 2,2′-(methylimino)diethanol.

, and either 1350 molecular weight hydroxyl terminated polybutadiene or 1000 molecular weight poly(tetramethylene oxide)

2 Systematic IUPAC name: poly(oxytetramethylene).

were synthesized. Zwitterionization was accomplished by quaternizing the tertiary amine of MDEA with 1,3-pro-panesultone. In Both series, IR analysis suggests that the sulfonate ion SO₃^? associates with the counter ion on the chain extender and the acidic hydrogen of the urethane linkage. Ammonium sulfonation shifts the soft segment T_g of polyether-based material to lower temperatures suggesting that ionization improves microphase separation. The soft segment T_g of the polybutadiene system is unaffected by ionization. IR dichroism measurements show that with increasing ammonium sulfonation both the hard and soft segments in the polyether-polyurethane zwitterionomers orient to a greater extent with deformation. In contrast, in the poly-butadiene-based zwitterionomers the orientability of the hard segment decreased with ionization while the soft segment showed significant chain alignment. Coupling the dichroism measurements to stress-strain results suggests that the hard segment domains of the polyether-polyurethane system possess more of an interconnected structure, while the polybutadiene-poly-urethane system contains hard segment domains which are largely isolated. The formation of different morphologies in the two systems of zwitterionomers may be due to the different interdomain surface tensions.     

Sequential reordering in condensation copolymers, 4. Crystallization-induced sequential reordering in poly(ethylene terephthalate)/polycarbonate copolymers as revealed by the behavior of the amorphous phases

An equimolar blend of poly(ethylene terephthalate) (PET) 3

1 Systematic IUPAC name: poly(oxyethyleneoxyterephthaloyl).

and bisphenol-A-polycarbonate (PC) 4

2 Systematic structure-based IUPAC nomenclature: poly(oxycarbonyloxy-1,4-phenylene-1-methylethylidene-1,4-phenylene).

is studied by dynamic-mechanical thermal analysis (DMTA) and X-ray scattering after thermal treatment that enables transesterification. As demonstrated by wide-angle X-ray scattering (WAXS) measurements, prolonged thermal treatment at 280°C gives rise to a copolymer that no longer reveals melting or crystallization. In accordance with previous reports, this effect is attributed to the formation of a random copolymer. Additional annealing of such samples below the melting temperature of PET results in restoration of the crystallization ability. This effect is explained by crystallization-induced sequential reordering from random to block copolymer by means of transreactions which closes the cycle of transformations from two homopolymers via block- and random copolymer back to a block copolymer. The behavior of the amorphous phases is studied by means of DMTA demonstrating that their glass transition temperatures T_g's vary in accordance with the crystallinity changes. The random copolymer is characterized by a more or less homogeneous amorphous phase. In contrast to this, the mechanical mixture and the two block copolymers (the initial and that with the restored blocky structure) show DMTA peaks of two amorphous phases, clearly separated and with distinct individual T_g's. Viscosity measurements also demonstrate that the random copolymer significantly differs in its viscosity as compared to all other samples. These results represent a further evidence for the effect of block restoration via crystallization-induced sequential reordering.     

Synthesis and reaction of polymethacrylate bearing cyclic carbonate moieties in the side chain

(2-Oxo-1,3-dioxolan-4-yl)methyl methacrylate ( 6 ) was prepared by fixation of CO₂ into glycidyl

1 Systematic name: 2,3-epoxypropyl.

methacrylate (2) . Pure 6 polymerized spontaneously at room temperature. Radical polymerization of 6 (purity 94%) was carried out at 60°C using 2,2′-azoisobutyronitrile as an initiator in dimethyl sulfoxide (DMSO) to give the corresponding homopolymer 1 (yield: 99%) which is soluble in DMSO and N,N-dimethylformamide. 1 was reacted with butylamien at room temperature in DMSO for 24 h to the corresponding polymethacrylate 13 (yield: 100%) having a hydroxyurethane

2 The systematic name for urethanes is carbamates.

group in the side chain. No reaction of the ester groups of 1 with butylamine was observed. This was also demonstrated by the model reaction of (2-oxo-1,3-dioxolan-4-yl)methyl isobutyrate (9) with butylamine in which the corresponding hydroxyurethanes 10 , 11 and 12 were isolated in 96% yield.     

Linear polymerization of endo-dicyclopentadiene initiated by metathesis catalysts

The polymerization of endo-dicyclopentadiene

1 Systematic name of endo-dicyclopentadiene is: tricyclo[5.2.1.0^2,6]deca-3,8-diene.

(endo-DCP) by the metathesis catalyst ReCl₅/(CH₃)₄ Sn gave a substantial yield of a linear polymer with high molecular weight and high content of cis double bonds. The kinetics of the early stage of the reaction was studied by calorimetry. The polymerization proceeds via an oligomerization reaction followed by the formation of polymers. A mechanistic scheme is proposed to explain the generation of the primary active species and the two-step polymerization process.     

Molecular structure of 1,7-dichlorotetradecaphenylheptasilane as a model of poly(diphenylsilane)

The molecular and crystal of 1,7-dichlorotetradecaphenylheptasilane Cl(SiPh₂)₇Cl

1 Dedicated to Prof. Dr. H. Sinn on the occasion of his 60th birthday

(I) was determined. The molecule has a helical conformation with the torsion angles SiSiSiSi in the range of 154°–162°. Crystal I is built of infinite polysilane chains extended along the [111] direction and separated by solvating benzene and toluene molecules.     

Unique mosaicism of tetraploidy and trisomy 8: Clinical,cytogenetic, and molecular findings in a live-born infant

We report on a live-born infant with mosaicism of tetraploidy and trisomy 8 who had craniofacial abnormalities, cardiac and genitourinary defects, agenesis of the corpus callosum, and anomalies of limbs. The infant died at age 14 weeks. Molecular studies were done on peripheral blood lymphocytes and cultured amniocytes to determine the origin of the cytogenetic abnormalities. On the basis of the results, we describe a possible mechanism to explain these abnormalities. To our knowledge, this infant represents the first reported case of mosaic trisomy 8 with a tetraploid cell line. © 1996 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Immune alterations in three mouse strains following 2-deoxy- -glucose administration

Using 2-deoxy- -glucose (2-DG)-induced stress, our laboratory has developed studies to define stress effects on immune responses. Here, we report effects of increasing doses of 2-DG on the immune response of BALB/c, C57BL/6 and BDF₁ mice 2 h after three injections of 0 to 2000 mg/kg of 2-DG. Female 4- to 5-week-old mice were euthanized and blood and spleens were collected. A suspension of partially purified mature T splenocytes was obtained by negative selection using J11.d2 antibodies. Glucose and corticosterone levels were measured in the plasma of each mouse. Splenocyte and mature T splenocyte suspensions were tested in in vitro proliferation assays with or without concanavalin A. Splenocytes were analyzed for the following cell-surface markers: CD3, TCR α/β, CD4, CD8 and major histocompatibility complex (MHC) Class II. Significant increases in blood glucose levels were observed in C57BL/6 and BALB/c strains with the highest 2-DG dose (p<0.05). Corticosterone levels were higher in BDF₁ mice and C57BL/6 mice following the administration of 1000 and 2000 mg/kg of 2-DG, respectively (p<0.01). In vitro proliferation of mature T splenocytes in the presence of concanavalin A was decreased in BDF₁ (p<0.05) but not in BALB/c and C57BL/6 mice. In addition, in BDF₁ mice the decrease was highly correlated with an increase of CD3+ and TCR α/β+ cells in the spleen. These results demonstrated high variability in the response of different mouse strains to 2-DG-induced stress.     

Effect of growth-promoting chemicals on growth,nitrogen fixation and heterocyst frequency of a blue-green alga

IAA

1 Abbreviations used: IAA, indole-3-acetic acid; NAA, α-naphthalene acetic acid; GA, Gibberellic acid; IPA, 3-indole propionic acid; IBA, 3-indole butyric acid; PAA, phenyl acetic acid

was found to stimulate growth, nitrogen fixation and pigment synthesis in Anabaena doliolum in all concentrations tested. Heterocyst frequency was stimulated up to a concentration of 50 ppm IAA. NAA stimulated growth and nitrogen fixation up to 10 ppm. GA promoted growth, pigment synthesis, heterocyst frequency and nitrogen fixation only up to a concentration of 2 ppm. Kinetin promoted growth up to 100 ppm and synthesis of pigments, while nitrogen fixation was stimulated up to 5 ppm.     

Liquid-crystalline polyimides, 23. Photoreactive,cholesteric copoly(ester-imide)s derived from 1,4-phenylenediacrylic acid and 4-aminobenzoic trimellitimide

The dichlorides of commercial 1,4-phenylenediacrylic acid

1 3,3′-(1,4-Phenylene)di-2-propenoic acid.

and N-(4-carboxyphenyl)-trimellitimide were polycondensed with a chiral spacer prepared from (S)-3-bromo-2-methylpropanol and 4-mercaptophenol. Optical microscopy revealed that all the resulting copoly(ester-imide)s form an enantiotropic cholesteric melt and adopt a Grandjean texture upon slight shearing. The WAXD powder patterns indicate the formation of a layered structure in the solid state. Irradiation with UV light of wavelength ? 360 nm allows crosslinking at any temperature above 25°C.