Are Gadolinium-Enhanced MR Sequences Needed in Simultaneous 18F-FDG-PET/MRI for Tumor Delineation in Head and Neck Cancer?

BACKGROUND AND PURPOSE: PET/MRI with 18F-FDG has demonstrated the advantages of simultaneous PET and MR imaging in head and neck cancer imaging, MRI allowing excellent soft-tissue contrast, while PET provides metabolic information. The aim of this study was to evaluate the added value of gadolinium contrast-enhanced sequences in the tumor delineation of head and neck cancers on 18F-FDG-PET/MR imaging. MATERIALS AND METHODS: Consecutive patients who underwent simultaneous head and neck 18F-FDG-PET/MR imaging staging or restaging followed by surgery were retrospectively included. Local tumor invasion and lymph node extension were assessed in 45 head and neck anatomic regions using 18F-FDG-PET/MR imaging by 2 rater groups (each one including a radiologist and a nuclear medicine physician). Two reading sessions were performed, one without contrast-enhanced sequences (using only T1WI, T2WI, and PET images) and a second with additional T1WI postcontrast sequences. The results were compared with the detailed histopathologic analysis, used as reference standard. The κ concordance coefficient between the reading sessions and sensitivity and specificity for each region were calculated. RESULTS: Thirty patients were included. There was excellent agreement between the contrast-free and postgadolinium reading sessions in delineating precise tumor extension in the 45 anatomic regions studied (Cohen κ = 0.96, 95% CI = [0.94-0.97], P < .001). The diagnostic accuracy did not differ between contrast-free and postgadolinium reading sessions, being 0.97 for both groups and both reading sessions. For the 2 rater groups, there was good sensitivity for both contrast-free (0.83 and 0.85) and postgadolinium reading sessions (0.88 and 0.90, respectively). Moreover, there was excellent specificity (0.98) for both groups and reading sessions. CONCLUSIONS: Gadolinium chelate contrast administration showed no added value for accurate characterization of head and neck primary tumor extension and could possibly be avoided in the PET/MR imaging head and neck workflow.

T-cell papulosis associated with B-cell malignancy: a distinctive clinicopathologic entity.

BACKGROUND: A distinctive eruption referred to as 'insect bite-like reaction' or 'eosinophilic dermatosis of haematological malignancy' has been described during the course of haematological B-cell malignancies (BCM). However, its clinical evolution, histopathological features and pathogenesis remain unclear. OBJECTIVES: To characterize this eruption and to investigate its pathogenesis and relationship with the underlying BCM. METHODS: In this multicenter retrospective study of the French Study Group on Cutaneous Lymphomas, 37 patients with a BCM and a cutaneous eruption consisting in chronic and/or recurrent papules, papulo-vesicles and/or nodules were included. Clinical, histopathological, immunohistochemical and molecular data were reviewed. RESULTS: No significant insect bite history or seasonal predominance was recorded. Patients had pruritic papules (81%), papulo-vesicles (43%) and nodules (38%), often predominated in the head and neck region (84%), without complete remission periods in most cases (57%). The predominant associated BCM was chronic lymphocytic leukaemia (73%). Histological and immunohistochemical review showed a dense dermal lymphocytic infiltrate predominantly composed of T lymphocytes (100%), with frequent eosinophils (77.6%); a perivascular and periadnexal (most often folliculotropic) pattern (77.6%), sometimes suggestive of a folliculotropic mycosis fungoides; clusters of tumour B cells were identified in 47% of cases using appropriate phenotyping markers. In 10/14 cases (71.4%) tested for B-cell IgH gene rearrangement, a B-cell clone was identified in skin lesions (identical to the blood clone in nine cases), whereas no T-cell clone was present. CONCLUSION: We propose the denomination 'T-cell papulosis associated with B-cell malignancy' (TCP-BCM) for this distinctive eruption. Although resulting in various histopathological pictures, it can be easily recognized by clinicians and may be identified by informed pathologists relying on some key features. An extravasation of tumour B cells with skin-homing properties associated with a secondary, predominant, T-cell immune reaction could explain the clinicopathologic aspect and the prolonged regressive and recurrent course of the disease.

Relationships between body dimensions, body weight, age, gender, breed and echocardiographic dimensions in young endurance horses.

BACKGROUND: The heart's physiological adaptation to aerobic training leads to an increase in heart chamber size, and is referred to as the Athlete's heart. However, heart dimensions are also related to body weight (BWT), body size, growth and (in some species) breed. There are few published data on the relationships between heart dimensions and growth or aerobic training in Arabian and Arabian-related endurance horses. Therefore the objective of the present study was to describe the influence of body dimensions (body length (BL), thoracic circumference (TC), withers height (WH)), BWT, age, gender, breed (purebred Arabians, part-bred Arabians, Anglo-Arabians, and Others) and the initiation of endurance training on echocardiographic measurements in competition-fit endurance horses aged 4 to 6 years. RESULTS: Most left atrial (LA) and left ventricular (LV) dimensions increased with age, whereas LA and LV functional indices did not. Although there was no gender difference for LV dimensions, females had larger LA dimensions. In terms of breed, Anglo-Arabians had the largest LV dimensions. Regression models indicated that the included explanatory factors had a weak influence on heart dimensions. Age, body dimensions, breed and gender showed the most consistent influence on LA dimensions, whereas BWT, breed and kilometres covered in competition showed the most consistent influence on LV dimensions. CONCLUSION: The increase in echocardiographic dimensions with age indicates on-going growth in our population of 4 to 6 year-old horses. We also observed small changes associated with the initiation of endurance training. Morphometric dimensions had a greater influence on LA dimensions, whereas LV dimensions were also influenced (albeit weakly) by parameters associated with exercise intensity. These results may therefore reflect early adaptations linked to the initiation of endurance training.

A hair on the tongue.

INTRODUCTION: Human hairs are generally localized on the cutaneous part of the head, neck, torso, armpits, pubis and limbs. Sometimes it can be found in an unusual localization and is then called heterotopic. OBSERVATION: A 30-year-old man presented with a hair in the middle of the dorsum of the tongue. It was decided to perform an excision under local anesthesia. DISCUSSION: Few reports exist that describe hair growing on mucosa. Only one other case has been published concerning the tongue.

Prevalence of West Nile virus neutralizing antibodies in wild birds from the Camargue area, southern France.

The Camargue area of southern France experienced the re-emergence of West Nile Virus (WNV) in the late summer of 2000 and 2004. Immediately preceding the 2004 outbreak, samples were collected from 432 birds of 32 different species captured in mist nets and from 201 Cattle Egret (Bubulcus ibis) nestlings sampled in their nests between 1 April and 12 June 2004. West Nile virus neutralizing titers of >/=40 were detected in 4.8% (95% confidence limit, 2.9-7.5%) of the adult birds and in 1.6% (0.3-4.6%) of the egret nestlings. Migratory passerines had a higher prevalence of WNV neutralizing antibodies (7.0%) than did resident and short-distance migratory passerines (0.8%), suggesting exposure to WNV or a related flavivirus during overwintering in Africa.

Magpies as hosts for West Nile virus, southern France.

European magpies (Pica pica) from southern France were tested for antibodies to West Nile virus (WNV) and viral shedding in feces during spring-autumn 2005. Results suggest that this peridomestic species may be a suitable sentinel species and a relevant target for additional investigations on WNV ecology in Europe.

[Liver steatosis and in-out of phase MR imaging: theory and clinical applications at 3T]. / Stéatose hépatique et séquence phase-opposition de phase: aspects théoriques et applications pratiques à 3T.

Liver steatosis may evolve into steatohepatitis then cirrhosis with related complications. It may also contribute to hepatocellular failure, sometimes fatal after major hepatectomy, especially in the setting of liver transplantation with living donor. Imaging must allow non-invasive detection and accurate quantification. In and out of phase MR imaging routinely performed in clinical practice is a simple and robust means of achieving these goals. In this article, we will review the histological, pathophysiologic, and clinical features of liver steatosis and the key points of in and out of phase pulse sequences and underlying physical principles. The T2* relaxation, cause of a loss of signal between both echo times must be taken into account. Echo times must be known for image interpretation, and optimized, especially at 3T. Finally, the T1 of lipids and water is different and causes T1 effects that may lead to quantification errors while being advantageous for image interpretation. The combination of these factors allows detection and quantification of liver steatosis in routine clinical practice.

Picosecond dynamics of T and R forms of aspartate transcarbamylase: a neutron scattering study.

E. coli aspartate transcarbamylase (ATCase) is a 310 kDa allosteric enzyme which catalyses the first committed step in pyrimidine biosynthesis. The binding of its substrates, carbamylphosphate and aspartate, induces significant conformational changes. This enzyme shows homotropic cooperative interactions between the catalytic sites for the binding of aspartate. This property is explained by a quaternary structure transition from T state (aspartate low affinity) to R state (aspartate high affinity) accompanied by a 5% increase of radius of gyration of ATCase. The same quaternary structure change is observed upon binding of the bisubstrate analogue PALA (N-(phosphonacetyl)-L-aspartate. Owing to the large incoherent neutron scattering cross-section of the hydrogen atom and the abundance of this element in proteins, inelastic neutron scattering gives a global view of protein dynamics as sensed via the individual motions of its hydrogen atoms. We present neutron scattering results of the local dynamics (few angstroms), at short time (few tens of picoseconds), of ATCase in T and R forms. Compared to the T form, we observe an increased mobility of the protein in the R form that we associate to an increase of accessible surface area to the solvent. Beyond this specific result, this highlights the key role of the accessible surface area (ASA) in dynamic contribution to inelastic neutron data in the picosecond time scale. In particular, we want to stress out (i) that a difference at the picosecond time scale does not allow to conclude to a difference in the dynamics at a longer time scale and to address whether the T state is looser than the R state (ii) how challenging is, any comparison in terms of general dynamics (tense or relaxed) between dynamic values deduced from experimental neutron data on proteins with different sequences and therefore ASA. This caveat holds particularly when comparing dynamics of a mesophile with the corresponding extremophile.

West Nile virus in Morocco, 2003.

West Nile virus (WNV) reemerged in Morocco in September 2003, causing an equine outbreak. A WNV strain isolated from a brain biopsy was completely sequenced. On the basis of phylogenetic analyses, Moroccan WNV strains isolated during the 1996 and 2003 outbreaks were closely related to other strains responsible for equine outbreaks in the western Mediterranean basin.

Cooperativity and high pressure: stabilization of the R conformation of the allosteric aspartate transcarbamylase under the influence of pressure.

The allosteric enzyme aspartate transcarbamylase (ATCase) from E. coli shows homotropic cooperative interactions between its six catalytic sites for the binding of the substrate aspartate. This cooperativity is explained by the transition of the enzyme from a conformation which has a low affinity for aspartate (T state) to a conformation with high affinity (R state). The crystallographic structures of these two conformations are known to a resolution of 2.5 A and 2.1 A, respectively, and they reveal an important difference in the quaternary structure of the protein. Enzyme kinetics under high pressure were used to study the transition between the two states. It appears that in the presence of a low concentration of aspartate, conditions under which the enzyme is essentially in the T state, pressure promotes the transition to the R state, the maximal effect being observed at 120 MPa. This transition is accompagnied by a significant deltaV. This observation is in accordance with the change in the protein surface exposed to the solvent, and with the increased number of water molecules bound to the protein. Since the partial specific volume of the enzyme does not change significantly during the T to R transition, the negative deltaV is only related to the change in hydration of the protein. This result emphasizes a significant role of the protein-solvent interactions in this important regulatory conformational change.

Cloning, expression, and structure analysis of carbamate kinase-like carbamoyl phosphate synthetase from Pyrococcus abyssi.

Pyrococcus abyssi, a hyperthermophilic archaeon found in the vicinity of deep-sea hydrothermal vents, grows optimally at temperatures around 100 degrees C. Carbamoyl phosphate synthetase (CPSase) from this organism was cloned and sequenced. The active 34-kDa recombinant protein was overexpressed in Escherichia coli when the host cells were cotransformed with a plasmid encoding tRNA synthetases for low-frequency Escherichia coli codons. Sequence homology suggests that the tertiary structure of P. abyssi CPSase, resembling its counterpart in Pyrococcus furiosus, is closely related to the catabolic carbamate kinases and is very different from the larger mesophilic CPSases. P. furiosus CPSase and carbamate kinase form carbamoyl phosphate by phosphorylating carbamate produced spontaneously in solution from ammonia and bicarbonate. In contrast, P. abyssi CPSase has intrinsic bicarbonate-dependent ATPase activity, suggesting that the enzyme can catalyze the phosphorylation of the isosteric substrates carbamate and bicarbonate.

Tryptophan residues at subunit interfaces used as fluorescence probes to investigate homotropic and heterotropic regulation of aspartate transcarbamylase.

The homotropic and heterotropic interactions in Escherichia coli aspartate transcarbamylase (EC 2.1.3.2) are accompanied by various structure modifications. The large quaternary structure change associated with the T to R transition, promoted by substrate binding, is accompanied by different local conformational changes. These tertiary structure modifications can be monitored by fluorescence spectroscopy, after introduction of a tryptophan fluorescence probe at the site of investigation. To relate unambiguously the fluorescence signals to structure changes in a particular region, both naturally occurring Trp residues in positions 209c and 284c of the catalytic chains were previously substituted with Phe residues. The regions of interest were the so-called 240's loop at position Tyr240c, which undergoes a large conformational change upon substrate binding, and the interface between the catalytic and regulatory chains in positions Asn153r and Phe145r supposed to play a role in the different regulatory processes. Each of these tryptophan residues presents a complex fluorescence decay with three to four independent lifetimes, suggesting that the holoenzyme exists in slightly different conformational states. The bisubstrate analogue N-phosphonacetyl-L-aspartate affects mostly the environment of tryptophans at position 240c and 145r, and the fluorescence signals were related to ligand binding and the quaternary structure transition, respectively. The binding of the nucleotide activator ATP slightly affects the distribution of the conformational substates as probed by tryptophan residues at position 240c and 145r, whereas the inhibitor CTP modifies the position of the C-terminal residues as reflected by the fluorescence properties of Trp153r. These results are discussed in correlation with earlier mutagenesis studies and mechanisms of the enzyme allosteric regulation.

Contribution of the bacterial endosymbiont to the biosynthesis of pyrimidine nucleotides in the deep-sea tube worm Riftia pachyptila.

The deep-sea tube worm Riftia pachyptila (Vestimentifera) from hydrothermal vents lives in an intimate symbiosis with a sulfur-oxidizing bacterium. That involves specific interactions and obligatory metabolic exchanges between the two organisms. In this work, we analyzed the contribution of the two partners to the biosynthesis of pyrimidine nucleotides through both the "de novo" and "salvage" pathways. The first three enzymes of the de novo pathway, carbamyl-phosphate synthetase, aspartate transcarbamylase, and dihydroorotase, were present only in the trophosome, the symbiont-containing tissue. The study of these enzymes in terms of their catalytic and regulatory properties in both the trophosome and the isolated symbiotic bacteria provided a clear indication of the microbial origin of these enzymes. In contrast, the succeeding enzymes of this de novo pathway, dihydroorotate dehydrogenase and orotate phosphoribosyltransferase, were present in all body parts of the worm. This finding indicates that the animal is fully dependent on the symbiont for the de novo biosynthesis of pyrimidines. In addition, it suggests that the synthesis of pyrimidines in other tissues is possible from the intermediary metabolites provided by the trophosomal tissue and from nucleic acid degradation products since the enzymes of the salvage pathway appear to be present in all tissues of the worm. Analysis of these salvage pathway enzymes in the trophosome strongly suggested that these enzymes belong to the worm. In accordance with this conclusion, none of these enzyme activities was found in the isolated bacteria. The enzymes involved in the production of the precursors of carbamyl phosphate and nitrogen assimilation, glutamine synthetase and nitrate reductase, were also investigated, and it appears that these two enzymes are present in the bacteria.

About the Keggin isomers: crystal structure of [N(C4H9)4]-gamma-[SiMo2W10O40]n- (n= 4 or 6).

The tetrabutylammonium gamma-dodecatungstosilicate has been crystallized in a 6/1 acetonitrile/water solvent. An X-ray single-crystal analysis was carried out on [N(C4H9)4]4-gamma-[SiW12O40] which crystallizes in the orthorhombic system, space group P2(1)2(1)2(1), with a = 19.0881(3) A, b = 21.4435(3) A, c = 26.0799(1) A, V = 10674.9(2) A3, Z = 4, and rho(calcd) = 2.392 g/cm3. The idealized C2v arrangement of the anion results from the rotation of 60 degrees of two trigonal [W3O13] groups in the Keggin anion. Taking as reference the geometrical characteristics of the Keggin anion, it appears that the bond lengths and bonds angles within the four [W3O13] groups are not significantly modified while the mu-oxo junctions between the two rotated groups and those between the two unrotated groups involve more acute and opened W-O-W angles, respectively. The syntheses and 183W NMR characterizations of the mixed gamma-[SiW10Mo2O40]n- compounds corresponding to the oxidized (Mo(VI); n = 4) and to the two electron-reduced (Mo(V); n = 6) anions are reported. Structural analysis by 183W NMR has proved unambiguously that the C2v structure of the gamma-[SiW10O36]8- subunit is retained in both the compounds. The electronic behavior of the series gamma-[SiW10M2E2O36]6- (M = Mo or W; E = O or S) is examined, compared and related to 183W NMR data.

Structural characterization and magnetic properties of sandwich-type tungstoarsenate complexes. Study of a mixed-valent VIV2/VV heteropolyanion.

Complexes K11Na1[As2W18(Mn(H2O))3O66]x27H2O (1) and Na12[As2W18(Co(H2O))3O66]x34H2O (2) have been characterized. 1 crystallizes in the orthorhombic space group Pnma, with a = 30.6484(4) A, b = 14.9946(2) A, and c = 19.17080(10) A (Z = 4), while 2 crystallizes in the monoclinic space group C2/c, with a = 14.124(2) A, b = 23.294(3) A, c = 32.247(3) A, and beta = 98.935(10) degrees (Z = 4). Structures of the anions of 1 and 2 are similar, the divalent metals adopting a square pyramidal environment. K11[As2W18(VO)3O66]x23H2O (3) crystallizes in the orthorhombic space group Pnma, with a = 30.6240(5) A, b = 14.9861(2) A, and c = 19.2651(3) A (Z = 4). The structure has revealed a disorder on two of the three metals linking the [alpha-AsW9O33]9- parts. For these two vanadium atoms, the V=O bonds are directed alternatively toward the inside or the outside of the [alpha-AsW9O33]9- cavity. The remaining vanadium shows a V=O bond always directed toward the outside of the cavity. Titration of VIV by CeIV revealed that 3 is the mixed-valent VIV2VV species. Magnetic measurements are in agreement with this formulation. The high-temperature molar magnetic susceptibility of a powdered sample of 3 clearly confirms the presence of two d1 centers. The two VIV are antiferromagnetically coupled, with J = -2.9 cm-1 and g = 1.93. Crystallographic data do not permit the location of the two VIV to be distinguished from the location of the VV. As expected, the Mn(II) are very weakly antiferromagnetically coupled in compound 1. The complex Na8[Ni(H2O)6]2[As2W18(Ni(H2O))3O66]x20H2O (4) has been synthesized. The anion crystallized with two octahedral [Ni(H2O)6]2+ as counterions. Magnetic data have been fitted assuming that the only exchange-coupled centers are the nickels of the polyanion. 4 exhibits an antiferromagnetic coupling with J = -1.7 cm-1, g = 2.27, and theta = -1.5 K.

Characterization of the aspartate transcarbamoylase from Methanococcus jannaschii.

The genes from the thermophilic archaeabacterium Methanococcus jannaschii that code for the putative catalytic and regulatory chains of aspartate transcarbamoylase were expressed at high levels in Escherichia coli. Only the M. jannaschii PyrB (Mj-PyrB) gene product exhibited catalytic activity. A purification protocol was devised for the Mj-PyrB and M. jannaschii PyrI (Mj-PyrI) gene products. Molecular weight measurements of the Mj-PyrB and Mj-PyrI gene products revealed that the Mj-PyrB gene product is a trimer and the Mj-PyrI gene product is a dimer. Preliminary characterization of the aspartate transcarbamoylase from M. jannaschii cell-free extract revealed that the enzyme has a similar molecular weight to that of the E. coli holoenzyme. Kinetic analysis of the M. jannaschii aspartate transcarbamoylase from the cell-free extract indicates that the enzyme exhibited limited homotropic cooperativity and little if any regulatory properties. The purified Mj-catalytic trimer exhibited hyperbolic kinetics, with an activation energy similar to that observed for the E. coli catalytic trimer. Homology models of the Mj-PyrB and Mj-PyrI gene products were constructed based on the three-dimensional structures of the homologous E. coli proteins. The residues known to be critical for catalysis, regulation, and formation of the quaternary structure from the well characterized E. coli aspartate transcarbamoylase were compared.

The evolutionary history of carbamoyltransferases: A complex set of paralogous genes was already present in the last universal common ancestor.

Forty-four sequences of ornithine carbamoyltransferases (OTCases) and 33 sequences of aspartate carbamoyltransferases (ATCases) representing the three domains of life were multiply aligned and a phylogenetic tree was inferred from this multiple alignment. The global topology of the composite rooted tree (each enzyme family being used as an outgroup to root the other one) suggests that present-day genes are derived from paralogous ancestral genes which were already of the same size and argues against a mechanism of fusion of independent modules. A closer observation of the detailed topology shows that this tree could not be used to assess the actual order of organismal descent. Indeed, this tree displays a complex topology for many prokaryotic sequences, with polyphyly for Bacteria in both enzyme trees and for the Archaea in the OTCase tree. Moreover, representatives of the two prokaryotic Domains are found to be interspersed in various combinations in both enzyme trees. This complexity may be explained by assuming the occurrence of two subfamilies in the OTCase tree (OTC alpha and OTC beta) and two other ones in the ATCase tree (ATC I and ATC II). These subfamilies could have arisen from duplication and selective losses of some differentiated copies during the successive speciations. We suggest that Archaea and Eukaryotes share a common ancestor in which the ancestral copies giving the present-day ATC II/OTC beta combinations were present, whereas Bacteria comprise two classes: one containing the ATC II/OTC alpha combination and the other harboring the ATC I/OTC beta combination. Moreover, multiple horizontal gene transfers could have occurred rather recently amongst prokaryotes. Whichever the actual history of carbamoyltransferases, our data suggest that the last common ancestor to all extant life possessed differentiated copies of genes coding for both carbamoyltransferases, indicating it as a rather sophisticated organism.