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Exposure fractionation effects for X-ray-induced dominant lethals in immature (stage-7) oocytes of Drosophila melanogaster: a re-analysis.

Young (0-4-h-old) Drosophila melanogaster females were X-irradiated with single or fractionated exposures over a range up to 6000 R and the induction of dominant lethals in immature (stage-7) oocytes was studied. The results show that (1) the frequencies of dominant lethals are higher after single than after fractionated exposures; (ii) at any given exposure level, the higher the number of fractions, the lower is the frequency of dominant lethals; (iii) consequently, the reduction in dominant lethality relative to single exposures increases with increasing number of fractions; and (iv) this relative reduction in dominant lethality approaches a maximum value when the magnitude of the single X-ray exposure approaches zero (i.e., when the egg survival after single X-ray exposure approaches 100%); the maxima, however, are different for the different fractionation regimes, being higher with increasing number of fractions. These findings are consistent with the assumed kinetics of X-ray induction of dominant lethality in stage-7 oocytes. It is shown that it is possible to predict the expected relative reduction in dominant lethality after fractionation, from appropriate dominant lethal data from single unfractionated exposures.

Animals↗

Early skin and lung reactions in breast cancer patients after radiotherapy: prospective study.

PURPOSE: The association between early radiological lung reactions consequent upon radiotherapy and patients' symptoms is not well established. This prospective study examined the association between symptoms experienced by the patient, clinical findings observed by the physician and reactions visible in chest X-ray as interpreted by a radiologist, as well as the association between skin or breast symptoms and lung symptoms induced by radiotherapy after different methods of surgery. METHODS: Altogether 207 consecutive breast cancer patients entered the trial between 1st October 1997 and 31st December 1998. Chest X-rays were taken at entry and 3, 6 and 12 months after radiotherapy. The frequency and intensity of symptoms as well as clinical and chest X-ray findings were assessed over time. RESULTS: Skin and breast symptoms were common after radiotherapy but seldom severe (9%). Lung reactions were seen in chest X-ray in 47% of patients in re-evaluation by a radiologist at 3 months. The frequency of lung or skin symptoms did not correlate with chest X-ray findings, but there was a significant correlation between skin and lung symptoms. Radiotherapy after conservative surgery for node-positive breast cancer caused lung reactions seen in chest X-ray more often than after mastectomy when using other techniques. The reactions were most common at the 6 month evaluation (P=0.01). Concomitant adjuvant chemo- or endocrine therapy did not significantly increase the incidence of lung reactions. CONCLUSIONS: Skin, breast and lung symptoms were frequent after radiotherapy, but there was no real association between lung or skin symptoms and chest X-ray findings. The only correlation noted was between skin or breast symptoms and lung symptoms experienced by patients. Radiotherapy after conservative surgery was more frequently linked to chest X-ray findings than radiotherapy after mastectomy. We conclude that routine chest X-ray after radiotherapy gives no more clinically relevant information than the symptoms of the patient and we do not recommend routine chest X-rays for that reason.

Adult↗

An evaluation of crystal structure of mannan I by X-ray powder diffraction and molecular mechanics studies.

The present study reports the re-examination of the crystal structure of mannan I by the X-ray powder diffraction study combined with the miniature crystal model simulation. A primary objective of this study was to investigate an adequate chain staggering position along the fiber axis. Among the several crystal structure models proposed for mannan I, that derived from the electron diffraction study of the single crystals was adopted as a starting model. The X-ray crystallographic residuals were calculated for the single crystal structure at different chain staggering positions, while the ab projection was kept invariant. In a similar fashion, the miniature crystal models consisting of seven mannotetraoses were constructed, each having different chain staggering values and the three-dimensional structures of all the models were subsequently optimized by using the MM3(92) program without introducing any constraint. Both the X-ray residual and lattice energy plots with respect to the chain staggering position showed the common minima around the -0.25 x c chain staggering. The minimum models were subjected to a search for preferred orientations of O2 and O6 hydroxyl groups. It was found that the hydroxyl groups present inside the minicrystal tended to rotate into particular orientations during the structure optimizations to form the O5-H-O2 and O3-H-O6 intermolecular hydrogen bonds between the adjacent oligomers in an alternative direction.

Cell Wall↗

Synthesis and characterization of novel 99gTc(V) and Re(V) complexes with water-soluble tetraaza diamido dipyridino ligands: single-crystal X-ray structural investigations of mono- and dinuclear complexes.

Rhenium and technetium are known for their useful applications in nuclear medicine with similar properties. In this study, new diamido dipyridino (N(4)) water-soluble ligands (2-C(5)H(4)NCH(2)NHCO)(2)CH(2), 1 (L(1)H2), (2-C(5)H(4)NNHNHCO)(2)CH(2), 2, and [2-C(5)H(4)N(+)(O)(-)CH(2)NHCO](2)CH(2), 3, were synthesized. Reaction of L(1)H2 with ReOCl(3)(PPh(3))(2) resulted in the novel six-coordinated rhenium(V) complex, trans-ReO(L(1))(OEt), 4. The complex was characterized by spectroscopic methods, and its X-ray crystallographic analysis revealed that rhenium is coordinated to four nitrogen atoms of the ligand and to two oxygen atoms from the deprotonated ethanol and the oxo group respectively in a distorted octahedral geometry. In solution, complex 4 was transformed to a new complex 5, which was proved to be the dinuclear complex mu-oxo [ReO(L(1))](2)O. Reaction of 1 with [n-Bu(4)N][ReOCl(4)] resulted in the neutral complex 6, trans-[ReO(L(1))]Cl. Similarly, when ligand 1 was reacted with [n-Bu(4)N][(99g)TcOCl(4)], the neutral trans-[(99)TcO(L(1))]Cl complex 7 was formed, which upon dissolution transformed into a cationic complex 8, trans-[(99)TcO(L(1))(OH(2))](+)Cl(-). The single-crystal X-ray structure of 8 reveals that the coordination sphere about technetium is a distorted octahedron with four nitrogen atoms in the equitorial plane, while doubly bonded oxygen and coordinated water occupy the apical positions. Further dissolution of 8 resulted in the formation of dinuclear mu-oxo [TcO(L(1))](2)O, 9. This study shows that Tc and Re have similar metal core structures in solution for diamido dipyridino systems, besides similarity in geometrical structure, proved by the X-ray structures on the same ligands.

Amines↗

gamma-Ray-induced apoptosis in transgenic mice with proliferative abnormalities in their intestinal epithelium: re-entry of villus enterocytes into the cell cycle does not affect their radioresistance but enhances the radiosensitivity of the crypt by inducing p53.

The radiosensitivity of proliferating crypt epithelial cells makes the gut a major limiting factor in the use of radiotherapy for treatment of abdominal cancers. As post-mitotic epithelial cells migrate from mouse small intestinal crypts to the base of adjacent villi, they rapidly lose their ability to undergo apoptosis in response to ionizing irradiation (IR). To determine whether this radioresistance reflects withdrawal from the cell cycle, we used a lineage-specific promoter to direct expression of wild type Simian virus 40 T antigen (SV40 TAg(Wt)) to villus, but not crypt, enterocytes in FVB/N transgenic mice. SV40 TAg(Wt) induced, pRB-dependent, re-entry into the cell cycle is not associated with the acquisition of IR-stimulated apoptosis 4 h or 24 h after 6 Gy or 12 Gy of gamma-irradiation. Co-expression of SV40 TAg(Wt) and K-ras(val12) produces dysplasia in cycling villus enterocytes but no shift towards apoptotic responsiveness to IR. These findings suggest that the radioresistance of villus enterocytes is not simply due to their cell cycle arrest and may be a reflection of their microenvironment. Remarkably, reentry of villus enterocytes to the cell cycle increases the radiosensitivity of the crypt epithelium without changing Bcl-2, Bcl-xL, Bak, or Bax expression. This effect is only manifest after IR and, based upon results obtained with mutant SV40 TAgs, depends upon reaching a critical level of proliferation in villus enterocytes. Like the normal crypt response to IR, the villus-derived enhancement of IR-stimulated crypt apoptosis is associated with an induction of p53 and Raf-1, and is dependent upon p53. Unlike the normal crypt response to IR, the p53 induction involves cells distributed throughout the crypt and the apoptotic response is not confined to the lower half of the crypt. These results indicate that signals initiated by cycling enterocytes can be transmitted to the crypt epithelium to induce p53 and influence their IR-induced apoptosis. Understanding the underlying signaling pathways may provide clues about how to modify a normal crypt's radiosensitivity for therapeutic benefit.

Animals↗

Novel carbohydrate-appended metal complexes for potential use in molecular imaging.

Seven discrete sugar-pendant diamines were complexed to the {M(CO)(3)}(+) ((99m)Tc/Re) core: 1,3-diamino-2-propyl beta-D-glucopyranoside (L(1)), 1,3-diamino-2-propyl beta-D-xylopyranoside (L(2)), 1,3-diamino-2-propyl alpha-D-mannopyranoside (L(3)), 1,3-diamino-2-propyl alpha-D-galactopyranoside (L(4)), 1,3-diamino-2-propyl beta-D-galactopyranoside (L(5)), 1,3-diamino-2-propyl beta-(alpha-D-glucopyranosyl-(1,4)-D-glucopyranoside) (L(6)), and bis(aminomethyl)bis[(beta-D-glucopyranosyloxy)methyl]methane (L(7)). The Re complexes [Re(L(1)-L(7))(Br)(CO)(3)] were characterized by (1)H and (13)C 1D/2D NMR spectroscopy which confirmed the pendant nature of the carbohydrate moieties in solution. Additional characterization was provided by IR spectroscopy, elemental analysis, and mass spectrometry. Two analogues, [Re(L(2))(CO)(3)Br] and [Re(L(3))(CO)(3)Br], were characterized in the solid state by X-ray crystallography and represent the first reported structures of Re organometallic carbohydrate compounds. Conductivity measurements in H(2)O established that the complexes exist as [Re(L(1)-L(7))(H(2)O)(CO)(3)]Br in aqueous conditions. Radiolabelling of L(1)-L(7) with [(99m)Tc(H(2)O)(3)(CO)(3)](+) afforded in high yield compounds of identical character to the Re analogues. The radiolabelled compounds were determined to exhibit high in vitro stability towards ligand exchange in the presence of an excess of either cysteine or histidine over a 24 h period.

Carbohydrates↗

Functionalization of glucose at position C-3 for transition metal coordination: organo-rhenium complexes with carbohydrate skeletons.

Novel 3-O-[1,2;5,6-di-O-isopropylidene-alpha-D-glucofuranose] and 3-O-[D-glucose] derivatives with an iminodiacetate (N,O,O), a histidinate, and an N-(acetetyl)picolylamine (N,N,O) chelating system for tridentate coordination of the organometallic M(CO)(3)-fragment (M = Tc, Re) have been prepared. The chelates were introduced and assembled through reductive amination starting from 3-O-[1,2;5,6-di-O-isopropylidene-alpha-D-glucofuranose]-acetaldehyde. After deprotection, the pyranose derivatives were reacted with the precursor [NEt(4)](2)[ReBr(3)(CO)(3)] to afford the corresponding organometallic complexes in yields between 54% and 94%. The NMR, MS, and IR analyses corroborated the tridentate coordination of the organometallic metal center exclusively via the synthetic chelates. In the case of the N-(acetyl)picolylamine derivative, the coordinative properties were further confirmed by X-ray structure analysis of the first Re(CO)(3)-D-glucofuranose complex. All glucose complexes unveiled good stability and solubility in organic and aqueous media.

Carbohydrates↗

Quasi-hexagonal molecular packing in collagen fibrils.

Collagen molecules in native 66.8 nm (D) periodic fibrils are widely believed to be assembled into discrete, rope-like substructures, or microfibrils. Several types of microfibril have been proposed (2, 4, 5, 7- and 8-stranded) mainly on the basis of information contained in the medium angle X-ray diffraction patterns of native tendon fibres. These patterns show a series of equatorial and near-equatorial Bragg reflections which indicate that the collagen molecules are arranged on a three-dimensional crystalline lattice. The 4-stranded, 5-stranded and 8-stranded microfibrils are D-periodic with approximate diameter 3.8 nm, and these and the 2-stranded model are supposed to be packed on a three-dimensional lattice whose basal unit cell, (approximately) perpendicular to the fibril axis, is tetragonal (or quasi-tetragonal)with side a, a square root 2 or 2a, where a is approximately 3.8 nm. In this paper we describe a re-interpretation of the X-ray data which leads to a new model for the crystalline regions of the fibril, based on quasi-hexagonal molecular packing without microfibrillar sub-structures, and hence having the character of a molecular crystal.

Animals↗

A new route to coordination complexes of nitroxyl (HN=O) via insertion reactions of nitrosonium triflate with transition-metal hydrides.

Nitrosonium triflate reacts with cold methylene chloride solutions of mer,trans-ReH(CO)3(PPh3)2 (1) with 1,1-insertion of NO+ into the Re-H bond to give the orange nitroxyl complex [mer,trans-Re(NH=O)(CO)3(PPh3)2][SO3CF3] (3) in 86% isolated yield. Use of [NO][PF6] or [NO][BF4] gives analogous insertion products at low temperature, which decompose on warning to ambient temperature to the fluoride complex mer,trans-ReF(CO)3(PPh3)2 (4). A related 1,1-insertion is observed in the reaction of 1 with [PhN2][PF6] in acetone that affords the yellow-orange phenyldiazene salt [mer,trans-Re(NH=NPh)(CO)3(PPh3)2][PF6] (2), which has been characterized by X-ray crystallographic methods. The methyl derivative mer,trans-Re(CH3)(CO)3(PPh3)2 (5) also undergoes a 1,1-insertion reaction with [NO][SO3CF3] to give the nitrosomethane adduct [mer,trans-Re{N(CH3)=O}(CO)3(PPh3)2][SO3CF3] (6) as red crystals in 75% yield. The nitroxyl complex [cis,trans-OsBr(NH=O)(CO)2(PPh3)2][SO3CF3] (8) can be similarly prepared as orange crystals in 52% yield by reaction of cis,trans-OsHBr(CO)2(PPh3)2 (7) with [NO][SO3CF3] in cold methylene chloride solution.

Journal Article↗

The polymorphs of calcium carbonate in human gall stones.

Gall stones from 64 patients that had been examined by X-ray diffraction in 1962 were re-examined in 1980 to find out if any phase transition of the calcium carbonate polymorphs had occurred. In the vast majority of cases, exactly the same powdered specimen was re-examined. In a few cases, more material was added or another stone from the same patient was analysed. There was no evidence that a phase transition had occurred upon storage of the specimens in room air, as had earlier been suggested in the literature. The three polymorphs of calcium carbonate, vaterite, aragonite and calcite therefore appear to precipitate in vivo mixed with each other in various proportions and/or with the other constituents of human gall stones. Complete dehydration of cholesterol monohydrate to cholesterol had occurred in all specimens.

Calcium Carbonate↗

Reactions of the Dirhenium(II) Complexes Re(2)X(4)(&mgr;-dppm)(2) (X = Cl, Br; dppm = Ph(2)PCH(2)PPh(2)) with Isocyanides. 11.(1) A Triply Bonded Dirhenium Complex Containing a Labile Acetonitrile Ligand. Synthesis, Structural Characterization, and Reactivity of [(XylNC)(CH(3)CN)ClRe(&mgr;-dppm)(2)ReCl(2)(CO)]O(3)SCF(3).

The reaction of the open bioctahedral form of Re(2)Cl(4)(&mgr;-dppm)(2)(CO)(CNXyl) (1), where XylNC = 2,6-dimethylphenyl isocyanide, with TlO(3)SCF(3) in the presence of acetonitrile proceeds with retention of stereochemistry at the dirhenium unit to afford the complex [Re(2)Cl(3)(&mgr;-dppm)(2)(CO)(CNXyl)(NCCH(3))]O(3)SCF(3) (3). The single-crystal X-ray structure determination of 3 shows that a Re&tbd1;Re bond is retained (the Re-Re distance is 2.378(3) Å) and that it is the chloride ligand trans to the XylNC ligand of 1 which is labilized. Complex 1 reacts with TlO(3)SCF(3) in a noncoordinating solvent to produce the unsymmetrical complex [Re(2)Cl(3)(&mgr;-dppm)(2)(CO)(CNXyl)]O(3)SCF(3) (2), through loss of this same chloride ligand of 1 and CO transfer from the adjacent Re center. The acetonitrile ligand of 3 is very labile and is readily displaced by XylNC and t-BuNC, with retention of stereochemistry, to produce complexes of stoichiometry [Re(2)Cl(3)(&mgr;-dppm)(2)(CO)(CNXyl)(CNR)]O(3)SCF(3) (R = Xyl, 4a; R = t-Bu, 4b). In a noncoordinating solvent, the nitrile ligand of 3 is lost and 2 is formed following CO transfer; this conversion is reversed upon the reaction of 2 with acetonitrile. When 3 is treated with CO, the acetonitrile ligand is again displaced, but in this instance the reaction is accompanied by a structure change to produce an edge-sharing bioctahedral complex of the type [Re(2)(&mgr;-CO)(&mgr;-Cl)(&mgr;-dppm)(2)Cl(2)(CO)(CNXyl)]O(3)SCF(3) (5).

Journal Article↗

Rapid re-expansion of a macroprolactinoma after early discontinuation of bromocriptine.

Prolactin (PRL)-secreting pituitary adenomas are the most common functioning pituitary tumors. Medical treatment with dopamine agonists is the therapy of choice for macroprolactinomas (> or = 10 mm). Withdrawal of bromocriptine after weeks or months of uninterrupted therapy has been associated with rapid tumor re-expansion as evidenced by x-ray and CT scanning of the pituitary region. We report a patient with a giant macroprolactinoma who had a dramatic response to bromocriptine (tumor volume shrinkage of 53% within a month) but rapid re-expansion to its original dimensions one week after discontinuation of bromocriptine. To our knowledge, this is the first time that the rapid shrinkage/re-expansion of a macroprolactinoma has been documented with serial MRI scans.

Adult↗

[Objective re-evaluation procedures in cases of possible diagnostic error].

Auxiliary diagnostic specialists such as clinical pathologists or radiodiagnosticians may be held liable by injured patients for erroneous diagnoses. Nearly always there will be a reconstruction of the situation in which the alleged misstake was made, and relevant facts will be tested against both professional and legal rules. The Court or one of the parties involved frequently ask an expert for re-evaluation of microscopic preparations, X-rays, etc. This objectivating evaluation requires a procedure that does justice to the original diagnostic situation and therefore should not be made by one single expert familiar with the chain of events. The results of the re-evaluation should be interpreted meticulously and their relative importance established by the Court.

Adult↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Use of restriction endonucleases to study relationships between DNA double-strand breaks, chromosomal aberrations and other end-points in mammalian cells.

Some of the cellular effects of radiation, such as mutations, chromosomal aberrations and cell killing, can be mimicked by inducing 'pure' double-strand breaks (dsb) in DNA of cells with restriction endonucleases (RE), although the chemical structure of the ends of dsb induced by RE are likely to differ from those induced by X-rays. Chromosomal aberrations are induced by treatment of cells with a variety of RE at all stages of the cell cycle. The frequency with which RE induce dsb in the DNA may be one factor determining the number of aberrations induced. However, the structure of the dsb generated may also determine the frequencies of aberrations induced. RE which generate 'cohesive-ended' dsb in the DNA have been shown to induce lower frequencies of aberrations than those causing 'blunt-ended' dsb, when inactivated Sendai virus is used to permeabilize cells. Other methods, involving a hypertonic shock to the treated cells, have led to results in which there is little or no difference in the effectiveness between the two types of dsb. It is argued here that the use of treatments which cause a hypertonic shock may influence the frequencies of aberrations induced.

Animals↗

The cobweb sign: percutaneous silastic long line tip placement in tributaries of superficial veins.

We report a method for preventing misplacement of percutaneous silastic catheters in superficial vein tributary or venous plexus. Catheters inserted less than the length calculated by surface anatomy measurement due to resistance were studied in three patients. Contrast X-rays (Omnipaque, Nycomed Imaging AS, Oslo, Norway) of the catheters was performed to confirm the catheter tip placement position. On initial assessment, the catheter tip placement was thought to be satisfactory and infusion of TPN commenced. Following signs of extravasation, re-examination of the contrast X-rays demonstrated that multiple thin rays of omnipaque could be traced in different directions like a cobweb. In the third infant, we recognised the "cobweb" sign and prospectively withdrew the catheter tip 2 cm. Repeat contrast X-ray confirmed that the catheter tip was in a major superficial vein, infusion continued without further complication. We conclude that when the "cobweb" sign is noticed then the catheter should be removed or withdrawn 2 to 3 cm and repeat contrast X-ray performed..

Catheterization, Central Venous↗

Previously undetected silicosis in New Jersey decedents.

BACKGROUND: Despite a reported decline in mortality and hospitalizations associated with silicosis [U.S. Department of Health and Human Services, 1999], this decline may be artifactual, stemming in part from underdiagnosis by physicians. METHODS: This study estimates, through radiological confirmation, the prevalence of unrecognized silicosis in a group of silica-exposed New Jersey decedents whose cause of death was chronic obstructive pulmonary disease (COPD), tuberculosis, or cor pulmonale. Two expert readers re-evaluated the chest X-rays of this group to determine the presence or absence of silicosis. The study population was considered to be presumptively exposed to silica dust by virtue of their usual industry of employment as listed on the death certificate. RESULTS: Radiographic evidence of silicosis was found in 8.5% of this population, and evidence of asbestosis was found in another 10.7%, for a total of 19.2%. CONCLUSIONS: The existence of previously unrecognized silicosis and asbestosis in 19.2% of this study group suggests that occupational lung disease is under-recognized and, hence, undercounted.

Aged↗

Certification of butyltins and phenyltins in marine sediment certified reference material by species-specific isotope-dilution mass spectrometric analysis using synthesized 118Sn-enriched organotin compounds.

A new marine sediment certified reference material, NMIJ CRM 7306-a, for butyltin and phenyltin analysis has been prepared and certified by the National Metrological Institute of Japan at the National Institute of Advanced Industrial Science and Technology (NMIJ/AIST). Candidate sediment material was collected at a bay near industrial activity in Japan. After air-drying, sieving, and mixing the material was sterilized with gamma-ray irradiation. The material was re-mixed and packaged into 250 glass bottles (15 g each) and these were stored in a freezer at -30 degrees C. Certification was performed by use of three different types of species-specific isotope-dilution mass spectrometry (SSID-MS)-SSID-GC-ICP-MS, SSID-GC-MS, and SSID-LC-ICP-MS, with 118Sn-enriched organotin compounds synthesized from 118Sn-enriched metal used as a spike. The 118Sn-enriched mono-butyltin (MBT), dibutyltin (DBT), and tributyltin (TBT) were synthesized as a mixture whereas the 118Sn-enriched di-phenyltin (DPhT) and triphenyltin (TPhT) were synthesized individually. Four different extraction methods, mechanical shaking, ultrasonic, microwave-assisted, and pressurized liquid extraction, were adopted to avoid possible analytical bias caused by non-quantitative extraction and degradation or inter-conversion of analytes in sample preparations. Tropolone was used as chelating agent in all the extraction methods. Certified values are given for TBT 44+/-3 microg kg(-1) as Sn, DBT 51 +/- 2 microg kg(-1) as Sn, MBT 67 +/- 3 microg kg(-1) as Sn, TPhT 6.9 +/- 1.2 microg kg(-1) as Sn, and DPhT 3.4 +/- 1.2 microg kg(-1) as Sn. These levels are lower than in other sediment CRMs currently available for analysis of organotin compounds.

Chemistry Techniques, Analytical↗