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[Inclusion compounds of collagen (author's transl)].

Small angle X-ray diagrams of collagen of rat tail treated with phospho tungstic acid or mercury chloride or cobalt- and uranyl-nitrate, osmiumoxide or hydroxy apatite show the same characteristic new reflections and reflection lines. The only remarkable difference exists between fibers treated under stress or relaxed. These experiments give new evidence for the paracrystallinity of collagen. More than 100 parallel aligned ca. 40 A thick octafibrils consist of 670 A long microparacrystals with 5 ca. 25 A thick soft segment layers. In these soft segments the holes of the octafibrils build up a lattice of vacancies with lattice cells of 38,5 x 35 x 135 A3 length. The above mentioned molecules penetrate from the lateral sides through the soft segments into these vacancies building up complexes with peptide groups of collagen. Under stress only a small amount of vacancies is occupied, statistically distributed over the vacancy-lattice, because the soft segments of the octafibrils are constricted. Without stress about 10 to 25% of the octafibrils within one paracrystal are filled up with sediments in the soft regions. With increasing precipitation finally 500 A long needles are formed of the inclusive material as detected by Höhling with the electron microscope in collagen of turkey tendon. The importance of the paracrystalline collagen model is emphasized to understand the biological process like the mineralisation of collagen and beta-keratin in organism or the activity of bone apatite in exchanging calcium ions.

Amino Acid Sequence↗

The mechanism of the transient depression of the erythropoietic rate induced in the rat by a single injection of uranyl nitrate.

With the purpose of assessing the effect of uranyl nitrate (UN) on the rate of erythropoiesis, 1 mg/kg of the compound was injected iv to adult female Wistar rats. The dosing vehicle was injected into control animals. A single injection of UN induced a transient depression of the rate of red cell volume 59Fe uptake, which reached its lowest value (68% depression) by the seventh postinjection day. By 14 days, 59Fe incorporation had returned to normal. The amount of iron going to erythroid tissue per hour, reticulocyte count, and immunoreactive erythropoietin concentration in both plasma and kidney extracts were also significantly depressed in UN-treated rats in relation to these values in vehicle-injected rats by the seventh postinjection day. Dose-response curves for exogenous erythropoietin (Epo) performed in polycythemic intact and UN-treated rats 7 days after drug injection revealed a significant depression of the response in UN-injected animals. Moreover, bone marrow cells obtained from rats pretreated with UN formed a reduced number of erythroid colonies in vitro in response to Epo. Therefore, possible mechanisms for the observed transient depression in the rate of erythropoiesis associated with acute UN treatment include decreased Epo production and direct or indirect damage of erythroid progenitor cells.

Animals↗

Ultrastructure of a temperature-sensitive rod- mutant of Bacillus subtilis.

Mutant 168ts-200B, resulting from nitrosoguanidine treatment of Bacillus subtilis 168 (trp(-) C2), exhibits a rod-to-sphere morphogenetic interconversion when the incubation temperature is 30 or 45 C, respectively. Ultrathin sections of rods grown at 30 C, after glutaraldehyde-osmium uranium-lead fixation and staining, show trilaminar cell walls with a well-developed underlying periplasm as in wild-type cells. However, the outer wall layer is irregular, and abnormal protrusions of wall material occur at the cross-walls. In contrast, cells growing at 45 C become rounded and are intersected randomly by irregular cross-walls which fail to split normally, resulting in large spherical masses. In these, the outer and inner wall layers and periplasm are lost, and the wall consists only of irregularly thickened and loosely organized middle layer. Wall ultrastructure is reversible in either direction as cell shape changes during temperature shifts. Mesosomes are rare and atypical at either temperature. It thus appears that cell wall ultrastructure is altered by the conditional (temperature-sensitive) mutation, and that loss of normal wall and submural organization is correlated with changes in cell size and shape as well as with inability to complete cell division. Preliminary studies after transformation of the mutant locus to another strain and growth at 45 C showed an increase in mucopeptide, loss of wall teichoic acid, failure of phage adsorption, and identical ultrastructural changes. The site of expression of the basic defect-be it in wall, submural region, or membrane-is undetermined.

Bacillus subtilis↗

Mammotomography with pinhole incomplete circular orbit SPECT.

UNLABELLED: Dedicated mammotomography with pinhole incomplete circular orbit (PICO) SPECT imaging of an uncompressed pendant breast was evaluated with small, very-high-stopping-power pinhole apertures. Comparisons were made with planar pinhole scintimammography. Enhanced 3-dimensional imaging performance with very-high-stopping-power apertures is thought to ultimately yield improved sensitivities for lesion detection and identification in breast disease. METHODS: Pinhole collimators made of high-density and high atomic number (184)W or depleted (238)U, with aperture diameters from 1 to 4 mm, were used to image 0.6- and 1.0-cm-diameter spherical lesions in a pendulous, uncompressed breast phantom in planar and PICO-SPECT modes. The breast was centered on the horizontal axis of rotation of an incomplete circular orbit. Lesion, breast and body, and myocardial activities (L:B:M) were included in the phantoms to simulate clinical imaging conditions with (99m)Tc (140 keV). Lesion contrasts and signal-to-noise ratios (SNRs) for all apertures were determined for near clinical acquisition times for L:B:M ratios of 12:1:20 and 7:1:25. A set of minidisks inserted in the breast phantom was scanned to determine sampling limitations at depth from the nipple. In an initial study, a patient with biopsy-confirmed breast carcinoma was injected with 960 MBq (99m)Tc-tetrofosmin and scanned 2 h later with planar pinhole and PICO-SPECT techniques. RESULTS: Overall, for PICO-SPECT imaging there were small differences in measured counting rate sensitivity (4.9%) and lesion contrast (8.8%) with larger SNR differences (20.8%) between tungsten and depleted uranium pinhole materials at this energy and these lesion sizes. Backgrounds from simulated myocardial uptake had minor contributions in all reconstructed image volumes because of the rapid sensitivity fall-off for pinhole apertures. An optimal aperture diameter between 2 and 3 mm was determined from peak SNR, indicating that these aperture sizes may have the best performance for lesions as small as 0.6 cm in diameter with activity concentration ratios of (99m)Tc similar to those currently seen in patients. Both lesions were visualized with PICO-SPECT better than with planar pinhole imaging, with respective contrast improvements >20 times the values obtained from planar imaging for the same pinholes. In the patient study, higher contrast (>6) visualization of the active tumor periphery was obtained with PICO-SPECT than with planar imaging. CONCLUSION: These results indicate that the enhanced spatial resolution of smaller apertures outweighs the loss in sensitivity in small lesion identification with PICO-SPECT. Although the imaging differences between investigated aperture types are small and some limitations to this imaging approach exist, dedicated PICO-SPECT of the breast appears to be an improved technique compared with conventional planar pinhole scintimammography. This technique provides enhanced contrast and SNR for imaging small lesions with the high-resolution pinhole apertures along with 3-dimensional localization of the lesions.

Breast↗

Laser flash photolysis evidence for styryl radical cation cyclization in the SET-induced photorearrangement of a p-methoxy-substituted 2-phenylallyl phosphite.

The SET-induced photorearrangement of dimethyl 2-(4-methoxyphenyl)allyl phosphite, 9 (UV light, uranium glass filter, 9,10-dicyanoanthracene (DCA), biphenyl), gives phosphonate 12 in 83% isolated yield. Laser flash irradiation at 355 nm of oxygen saturated solutions of phosphite 9 containing DCA and biphenyl generates the transient UV spectrum of the biphenyl radical cation that is quenched by electron transfer from phosphite 9 (k(q) = 8.9 x 10(9) M(-1) s(-1) at 20 degrees C) to form the 4-methoxystyryl cation 10. The UV spectrum of 10 decays by a measured first-order rate constant of 8.0 x 10(6) s(-1), presumably to generate the cyclic distonic radical cation 11. Intermediate 10 was further characterized by measurement of the second-order rate constants for its reaction with azide, chloride, and bromide ions and with the neutral nucleophile trimethyl phosphite. This study provides the first spectroscopic evidence regarding the proposed mechanism (Schemes 1 and 2) for the SET-induced photorearrangements of dimethyl 2-arylallyl phosphites to the corresponding 2-arylallylphosphonates. Moreover, absolute rate constants for the intramolecular trapping of alkene radical cations have seldom been measured. The removal of the electron from the styryl moiety of phosphite 9, rather than from phosphorus, and the detectability of 10 arise from the stabilizing effect of the 4-methoxy substituent. These results, however, do not allow conclusions to be made concerning the site of removal of an electron in the SET-induced photorearrangement of dimethyl 2-phenylallyl phosphite 1 to phosphonate 6.

Allyl Compounds↗

Molecular analysis of hprt mutations generated in Chinese hamster ovary EM9 cells by uranyl acetate, by hydrogen peroxide, and spontaneously.

Naturally occurring uranium and depleted uranium (DU) are believed to be health hazards by virtue of both their chemical and radiological properties. The mechanism(s) behind uranium's chemotoxic effects has yet to be elucidated. Previous work has shown that DU, as uranyl acetate (UA), was mutagenic at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus in XRCC1-deficient CHO EM9 cells. The purpose of the current study was to characterize the mutations induced by UA at the hprt locus of CHO EM9 cells and compare the mutation spectrum of UA with those of hydrogen peroxide and spontaneous mutations in the same line. The hypothesis being tested was that if DU as UA is chemically genotoxic then the mutation spectrum induced by the heavy metal should be distinct from that produced spontaneously or by H2O2. A total of 59 UA-induced, 38 spontaneous, and 45 H2O2-induced mutations were identified. Base substitutions comprised 29%, 42%, and 16% of UA, spontaneous, and H2O2 mutants, respectively. The frequency of G --> T or C --> A substitutions was not significantly different in spontaneous or H2O2-induced mutants than in UA-induced mutants, suggesting a possible role for 8-oxodG damage in UA mutagenesis. However, the observation that UA produced significantly more major genomic rearrangements (multiexon insertions and deletions) than occurred spontaneously suggests the possibility that DNA strand breaks or crosslinks could also be UA-induced mutagenic lesions. The unique mutation spectrum elicited by exposure to UA suggests that UA generates mutations in ways that are different from spontaneous and free radical as well as radiological mechanisms.

Alpha Particles↗

Embedded weapons-grade tungsten alloy shrapnel rapidly induces metastatic high-grade rhabdomyosarcomas in F344 rats.

Continuing concern regarding the potential health and environmental effects of depleted uranium and lead has resulted in many countries adding tungsten alloy (WA)-based munitions to their battlefield arsenals as replacements for these metals. Because the alloys used in many munitions are relatively recent additions to the list of militarily relevant metals, very little is known about the health effects of these metals after internalization as embedded shrapnel. Previous work in this laboratory developed a rodent model system that mimicked shrapnel loads seen in wounded personnel from the 1991 Persian Gulf War. In the present study, we used that system and male F344 rats, implanted intramuscularly with pellets (1 mm times 2 mm cylinders) of weapons-grade WA, to simulate shrapnel wounds. Rats were implanted with 4 (low dose) or 20 pellets (high dose) of WA. Tantalum (20 pellets) and nickel (20 pellets) served as negative and positive controls, respectively. The high-dose WA-implanted rats (n = 46) developed extremely aggressive tumors surrounding the pellets within 4-5 months after implantation. The low-dose WA-implanted rats (n = 46) and nickel-implanted rats (n = 36) also developed tumors surrounding the pellets but at a slower rate. Rats implanted with tantalum (n = 46), an inert control metal, did not develop tumors. Tumor yield was 100% in both the low- and high-dose WA groups. The tumors, characterized as high-grade pleomorphic rhabdomyosarcomas by histopathology and immunohistochemical examination, rapidly metastasized to the lung and necessitated euthanasia of the animal. Significant hematologic changes, indicative of polycythemia, were also observed in the high-dose WA-implanted rats. These changes were apparent as early as 1 month postimplantation in the high-dose WA rats, well before any overt signs of tumor development. These results point out the need for further studies investigating the health effects of tungsten and tungsten-based alloys.

Alloys↗

Gas-phase transuranium chemistry: reactions of actinide ions with alcohols and thiols.

The laser ablation with prompt reaction and detection method was employed to provide a survey of some gas-phase reactions of actinide (M = U, Np, Pu and Am) and lanthanide (M = Tb and Tm) ions, M(+) and MO(1,2)(+), with alcohols, thiols and ethers. Particular attention was given the changing behavior in progressing across the actinide series beyond uranium. With alcohols, ROH, major products included hydroxides and alkoxides, M(OH)(1,2)(+), M(OR)(1,2)(+), MO(OH)(+) and MO(OR)(+); these products are presumed to have resulted from RO&bond;H and R&bond;OH bond cleavage by ablated M(+) and MO(+). The abundance distributions for these elementary products reflected the decrease in stabilities of high oxidation states between U and Am. Other alcohol reaction products included electrostatically bonded adducts, such as HO&bond;Np(+)ellipsisC(3)H(7)OH, sigma-bonded organometallics, such as HO&bond;Pu(+)&bond;C(2)H(5), and pi-bonded organometallics, such as Np(+)&bond;eta(3)-¿C(3)H(5)¿. In view of the inability of actinide and lanthanide ions to dehydrogenate alkanes, the exhibition of dehydrogenation of the alkyl chain of alcohols, as in HO-Pu(+)-C(3)H(5)O from propanol, suggests a non-insertion mechanism involving complexation of the reactant ion to the alcohol. Whereas O abstraction products from ROH were obfuscated by directly ablated MO(1,2)(+), S abstraction from thiols, RSH, was manifested by the appearance of MS(+), MS(2)(+) and MOS(+). In analogy with OH abstraction from alcohols to produce metal hydroxides, SH abstraction from thiols resulted in hydrosulfides, including Am(SH)(+) and Np(SH)(2)(+). In addition to several other reaction pathways with the thiol reagents, products presumed to be thiolates included Am(C(3)H(7)S)(+) and NpO(C(3)H(7)S) from propanethiol. A primary product of reaction with dimethyl ether were methoxides resulting from C--O bond cleavage, including Am(OCH(3))(+) and Np(OCH(3))(2)(+). With methyl vinyl ether, more complex pathways were exhibited, most of which corresponded to the elimination of stable organic molecules. An ancillary result was the discovery of several small oxide clusters, Am(2)O(n)(+), Np(2)O(n)(+) and AmNpO(n)(+). The compositions and abundance distributions of these clusters reflected the propensity of Np to exist in higher oxidation states than Am; the dominant binary clusters were Am(2)O(2)(+) and Np(2)O(3)(+).

Actinoid Series Elements↗