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Biomedical subjects

R W Carlson

Publications and source records attributed to R W Carlson.

At least 19 recordsLinked to original sources
PubMed2005

142Nd evidence for early (>4.53 Ga) global differentiation of the silicate Earth.

New high-precision samarium-neodymium isotopic data for chondritic meteorites show that their 142Nd/144Nd ratio is 20 parts per million lower than that of most terrestrial rocks. This difference indicates that most (70 to 95%) of Earth's mantle is compositionally similar to the incompatible element-depleted source of mid-ocean ridge basalts, possibly as a result of a global differentiation 4.53 billion years ago (Ga), within 30 million years of Earth's formation. The complementary enriched reservoir has never been sampled and is probably located at the base of the mantle. These data influence models of Earth's compositional structure and require revision of the timing of global differentiation on Earth's Moon and Mars.

Journal Article↗
PubMed2004

Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis.

PURPOSE: The modulation of fluorouracil (FU) by folinic acid (leucovorin [LV]) has been shown to be effective in terms of tumor response rate in patients with advanced colorectal cancer, but a meta-analysis of nine trials previously published by our group failed to demonstrate a statistically significant survival difference between FU and FU-LV. We present an update of the meta-analysis, with a longer follow-up and the inclusion of 10 newer trials. PATIENTS AND METHODS: Analyses are based on individual data from 3,300 patients randomized in 19 trials on an intent-to-treat basis. Two trials had multiple comparisons, leading to a total of 21 pair-wise comparisons. FU doses were similar in both arms in 10 pair-wise comparisons, 15% to 33% higher in the FU-alone arm in six comparisons, and more than 66% higher in five comparisons. RESULTS: Overall analysis showed a two-fold increase in tumor response rates (11% for FU-LV v 21% for FU-LV v 11% for FU [corrected] alone; odds ratio, 0.53; 95% CI, 0.44 to 0.63; P <.0001) and a small but statistically significant overall survival benefit for FU-LV over FU alone (median survival, 11.7 v 10.5 months, respectively; hazards ratio, 0.90; 95% CI, 0.87 to 0.94; P =.004), which were primarily seen in the first year. We observed a significant interaction between treatment benefit and dose of FU, with tumor response and overall survival advantages of FU-LV over FU-alone being restricted to trials in which a similar dose of FU was prescribed in both arms. CONCLUSION: This updated analysis demonstrates, on a large data set, that FU-LV improves both response rate and overall survival compared with FU alone and that this benefit is consistent across various prognostic factors.

Aged↗
PubMed2003

Archaean ultra-depleted komatiites formed by hydrous melting of cratonic mantle.

Komatiites are ultramafic volcanic rocks containing more than 18 per cent MgO (ref. 1) that erupted mainly in the Archaean era (more than 2.5 gigayears ago). Although such compositions occur in later periods of Earth history (for example, the Cretaceous komatiites of Gorgona Island), the more recent examples tend to have lower MgO content than their Archaean equivalents. Komatiites are also characterized by their low incompatible-element content, which is most consistent with their generation by high degrees of partial melting (30-50 per cent). Current models for komatiite genesis include the melting of rock at great depth in plumes of hot, diapirically rising mantle or the melting of relatively shallow mantle rocks at less extreme, but still high, temperatures caused by fluxing with water. Here we report a suite of ultramafic lava flows from the Commondale greenstone belt, in the southern part of the Kaapvaal Craton, which represents a previously unrecognized type of komatiite with exceptionally high forsterite content of its igneous olivines, low TiO(2)/Al(2)O(3) ratio, high silica content, extreme depletion in rare-earth elements and low Re/Os ratio. We suggest a model for their formation in which a garnet-enriched residue left by earlier cratonic volcanism was melted by hydration from a subducting slab.

Journal Article↗
PubMed2003

Three genes encoding for putative methyl- and acetyltransferases map adjacent to the wzm and wzt genes and are essential for O-antigen biosynthesis in Rhizobium etli CE3.

The elucidation of the structure of the O-antigen of Rhizobium etli CE3 predicts that the R. etli CE3 genome must contain genes encoding acetyl- and methyltransferases to confer the corresponding modifications to the O-antigen. We identified three open reading frames (ORFs) upstream of wzm, encoding the membrane component of the O-antigen transporter and located in the lps alpha-region of R. etli CE3. The ORFs encode two putative acetyltransferases with similarity to the CysE-LacA-LpxA-NodL family of acetyltransferases and one putative methyltransferase with sequence motifs common to a wide range of S-adenosyl-L-methionine-dependent methyltransferases. Mutational analysis of the ORFs encoding the putative acetyltransferases and methyltransferase revealed that the acetyl and methyl decorations mediated by these specific enzymes are essential for O-antigen synthesis. Composition analysis and high performance anion exchange chromatography analysis of the lipopolysaccharides (LPSs) of the mutants show that all of these LPSs contain an intact core region and lack the O-antigen polysaccharide. The possible role of these transferases in the decoration of the O-antigen of R. etli is discussed.

ATP-Binding Cassette Transporters↗
PubMed2002

Isolation and characterization of the major nod factor of Bradyrhizobium japonicum strain 532C.

Bradyrhizobium japonicum 532C nodulates soybean effectively under cool Canadian spring conditions and is used in Canadian commercial inoculants. The major lipo-chitooligosaccharide (LCO), bacteria-to-plant signal was characterized by HPLC, FAB-mass spectroscopy MALDI-TOF mass spectroscopy and revealed to be LCO Nod Bj-V (C18:1, MeFuc). This LCO is produced by type I strains of B. japonicum and is therefore unlikely to account for this strains superior ability to nodulate soybean under Canadian conditions. We also found that use of yeast extract mannitol medium gave similar results to that of Bergerson minimal medium.

Bradyrhizobium↗
PubMed2001

The early evolution of the inner solar system: a meteoritic perspective.

Formation of the solar system may have been triggered by a stellar wind. From then on, the solar system would have followed a conventional evolutionary path, including the formation of a disk and bipolar jets. The now extinct short-lived radionuclides beryllium-10 and, possibly, manganese-53 that were present in meteorites probably resulted from energetic particle irradiation within the solar system. Calcium-aluminum-rich inclusions (the oldest known solar system solids) and chondrules could have been produced by the bipolar jets, but it is more likely that they formed during localized events in the asteroid belt. The chondritic meteorites formed within the temperature range (100 to 400 kelvin) inferred for the midplane of classical T Tauri disks at 2 to 3 astronomical units from their central stars. However, these meteorites may retain a chemical memory of earlier times when midplane temperatures were much higher. Dissipation of the solar nebula occurred within a few million years of solar system formation, whereas differentiation of asteroidal-sized bodies occurred within 5 to 15 million years. The terrestrial planets took approximately 100 million years to form. Consequently, they would have accreted already differentiated bodies, and their final assembly was not completed until after the solar nebula had dispersed. This implies that water-bearing asteroids and/or icy planetesimals that formed near Jupiter are the likely sources of Earth's water.

Journal Article↗
PubMed2001

Structural characterization of the Pseudomonas aeruginosa 1244 pilin glycan.

An antigenic similarity between lipopolysaccharide (LPS) and glycosylated pilin of Pseudomonas aeruginosa 1244 was noted. We purified a glycan-containing molecule from proteolytically digested pili and showed it to be composed of three sugars and serine. This glycan competed with pure pili and LPS for reaction with an LPS-specific monoclonal antibody, which also inhibited twitching motility by P. aeruginosa bearing glycosylated pili. One-dimensional NMR analysis of the glycan indicated the sugars to be 5N beta OHC(4)7NfmPse, Xyl, and FucNAc. The complete proton assignments of these sugars as well as the serine residue were determined by COSY and TOCSY. Electrospray ionization mass spectrometry (MS) determined the mass of this molecule to be 771.5. The ROESY NMR spectrum, tandem MS/MS analysis, and methylation analysis provided information on linkage and the sequence of oligosaccharide components. These data indicated that the molecule had the following structure: alpha-5N beta OHC(4)7NFmPse-(2-->4)beta-Xyl-(1-->3)-beta-FucNAc-(1-->3)-beta-Ser.

Antigens, Bacterial↗
PubMed2001

Identification of an ATP-binding cassette transporter for export of the O-antigen across the inner membrane in Rhizobium etli based on the genetic, functional, and structural analysis of an lps mutant deficient in O-antigen.

For O-antigen lipopolysaccharide (LPS) synthesis in bacteria, transmembrane migration of undecaprenyl pyrophosphate-bound O-antigen oligosaccharide subunits or polysaccharide occurs before ligation to the core region of the LPS molecule. In this study, we identified by mutagenesis an ATP-binding cassette transporter in Rhizobium etli CE3 that is likely responsible for the translocation of the O-antigen across the inner plasma membrane. Mutant FAJ1200 LPS lacks largely the O-antigen, as shown by SDS-polyacrylamide gel electrophoresis and confirmed by immunoblot analysis. Furthermore, LPS isolated from FAJ1200 is totally devoid of any O-chain glycosyl residues and contains only those glycosyl residues that can be expected for the inner core region. The membrane component and the cytoplasmic ATP-binding component of the ATP-binding cassette transporter are encoded by wzm and wzt, respectively. The Tn5 transposon in mutant FAJ1200 is inserted in the wzm gene. This mutation resulted in an Inf- phenotype in bean plants.

ATP-Binding Cassette Transporters↗
PubMed2001

Supportive-expressive group therapy and distress in patients with metastatic breast cancer: a randomized clinical intervention trial.

BACKGROUND: Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control. METHODS: Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population. RESULTS: Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition. CONCLUSION: Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.

Adaptation, Psychological↗
PubMed2001

Lipid A and O-chain modifications cause Rhizobium lipopolysaccharides to become hydrophobic during bacteroid development.

Modifications to the lipopolysaccharide (LPS) structure caused by three different growth conditions were investigated in the pea-nodulating strain Rhizobium leguminosarum 3841. The LPSs extracted by hot phenol-water from cultured cells fractionated into hydrophilic water and/or hydrophobic phenol phases. Most of the LPSs from cells grown under standard conditions extracted into the water phase, but a greater proportion of LPSs were extracted into the phenol phase from cells grown under acidic or reduced-oxygen conditions, or when isolated from root nodules as bacteroids. Compared with the water-extracted LPSs, the phenol-extracted LPSs contained greater degrees of glycosyl methylation and O-acetylation, increased levels of xylose, glucose and mannose and increased amounts of long-chain fatty acids attached to the lipid A moiety. The water- and phenol-phase LPSs also differed in their reactivity with monoclonal antibodies and in their polyacrylamide gel electrophoretic banding patterns. Phenol-extracted LPSs from rhizobia grown under reduced-oxygen conditions closely resembled the bulk of LPSs isolated from pea nodule bacteria (i.e. mainly bacteroids) in their chemical properties, reactivities with monoclonal antibodies and extraction behaviour. This finding suggests that, during symbiotic bacteroid development, reduced oxygen tension induces structural modifications in LPSs that cause a switch from predominantly hydrophilic to predominantly hydrophobic molecular forms. Increased hydrophobicity of LPSs was also positively correlated with an increase in the surface hydrophobicity of whole cells, as shown by the high degree of adhesion to hydrocarbons of bacterial cells isolated from nodules or from cultures grown under low-oxygen conditions. The implications of these LPS modifications are discussed for rhizobial survival and function in different soil and in planta habitats.

Bacterial Adhesion↗
PubMed2001

The structure of the lipooligosaccharide (LOS) from the alpha-1,2-N-acetyl glucosamine transferase (rfaK(NMB)) mutant strain CMK1 of Neisseria meningitidis: implications for LOS inner core assembly and LOS-based vaccines.

The inner core structures of the lipooligosaccharides (LOS) of Neisseria meningitidis are potential vaccine candidates because both bactericidal and opsonic antibodies can be generated against these epitopes. In an effort to better understand LOS biosynthesis and the potential immunogenicity of the LOS inner core, we have determined the LOS structure from a meningococcal rfaK mutant CMK1. The rfaK gene encodes the transferase that adds an alpha-N-acetylglucosaminosyl residue to O-2 of the inner core heptose (Hep) II of the LOS. The LOS oligosaccharide from this mutant was previously shown to contain only Hep, 3-deoxy-D-manno-2-octulosonic acid (Kdo), and multiple phosphoethanolamine (PEA) substituents (Kahler et al., 1996a, J. Bacteriol., 178, 1265-1273). The complete structure of the oligosaccharide (OS) component of the LOS from mutant CMK1 was determined using glycosyl composition and linkage analyses, and 1H, 13C, and 31P nuclear magnetic resonance spectroscopy. The CMK1 OS structure contains a PEA group at O-3 of Hep II in place of the usual glucosyl residue found at this position in the completed L2 LOS glycoform from the parent NMB strain. The PEA group at O-6 of Hep II, however, is present in both the CMK1 mutant LOS and parental NMB L2 LOS structures. The structure of the OS from CMK1 suggests that PEA substituents are transferred to both the O-3 and O-6 positions of Hep II prior to: (1) the incorporation of the alpha-GlcNAc on Hep II; (2) the synthesis of the alpha-chain on Hep I; and (3) the substitution of the glycosyl residue at the O-3 Hep II, which distinguishes L2 and L3 immunotypes. The LOS structure of the CMK1 mutant makes it a candidate immunogen that could generate broadly cross-reactive inner-core LOS antibodies.

Bacterial Proteins↗
PubMed2001

Genetic locus required for antigenic maturation of Rhizobium etli CE3 lipopolysaccharide.

Rhizobium etli modifies lipopolysaccharide (LPS) structure in response to environmental signals, such as low pH and anthocyanins. These LPS modifications result in the loss of reactivity with certain monoclonal antibodies. The same antibodies fail to recognize previously isolated R. etli mutant strain CE367, even in the absence of such environmental cues. Chemical analysis of the LPS in strain CE367 demonstrated that it lacked the terminal sugar of the wild-type O antigen, 2,3,4-tri-O-methylfucose. A 3-kb stretch of DNA, designated as lpe3, restored wild-type antigenicity when transferred into CE367. From the sequence of this DNA, five open reading frames were postulated. Site-directed mutagenesis and complementation analysis suggested that the genes were organized in at least two transcriptional units, both of which were required for the production of LPS reactive with the diagnostic antibodies. Growth in anthocyanins or at low pH did not alter the specific expression of gusA from the transposon insertion of mutant CE367, nor did the presence of multiple copies of lpe3 situated behind a strong, constitutive promoter prevent epitope changes induced by these environmental cues. Mutations of the lpe genes did not prevent normal nodule development on Phaseolus vulgaris and had very little effect on the occupation of nodules in competition with the wild-type strain.

Carbohydrate Sequence↗
PubMed2000

Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis. Meta-Analysis Group in Cancer.

BACKGROUND: Treatment of advanced colorectal cancer has progressed substantially. However, improvements in response rates have not always translated into significant survival benefits. Doubts have therefore been raised about the usefulness of tumour response as a clinical endpoint. METHODS: This meta-analysis was done on individual data from 3791 patients enrolled in 25 randomised trials of first-line treatment with standard bolus intravenous fluoropyrimidines versus experimental treatments (fluorouracil plus leucovorin, fluorouracil plus methotrexate, fluorouracil continuous infusion, or hepatic-arterial infusion of floxuridine). Analyses were by intention to treat. FINDINGS: Compared with bolus fluoropyrimidines, experimental fluoropyrimidines led to significantly higher tumour response rates (454 responses among 2031 patients vs 209 among 1760; odds ratio 0.48 [95% CI 0.40-0.57], p<0.0001) and better survival (1808 deaths among 2031 vs 1580 among 1760; hazard ratio 0.90 [0.84-0.97], p=0.003). The survival benefits could be explained by the higher tumour response rates. However, a treatment that lowered the odds of failure to respond by 50% would be expected to decrease the odds of death by only 6%. In addition, less than half of the variability of the survival benefits in the 25 trials could be explained by the variability of the response benefits in these trials. INTERPRETATION: These analyses confirm that an increase in tumour response rate translates into an increase in overall survival for patients with advanced colorectal cancer. However, in the context of individual trials, knowledge that a treatment has benefits on tumour response does not allow accurate prediction of the ultimate benefit on survival.

Antimetabolites, Antineoplastic↗
PubMed2000

Structural characterization of the O-antigenic polysaccharide of the lipopolysaccharide from Rhizobium etli strain CE3. A unique O-acetylated glycan of discrete size, containing 3-O-methyl-6-deoxy-L-talose and 2,3,4-tri-O-,methyl-l fucose.

The O-antigenic polysaccharide of the Rhizobium etli CE3 lipopolysaccharide (LPS) was structurally characterized using chemical degradations (Smith degradation and beta-elimination of uronosyl residues) in combination with alkylation analysis, electrospray, and matrix-assisted laser desorption ionization-time of flight mass spectrometry, tandem mass spectrometry, and (1)H COSY and TOCSY nuclear magnetic resonance spectroscopy analyses of the native polysaccharide and the derived oligosaccharides. The polysaccharide was found to be a unique, relatively low molecular weight glycan having a fairly discrete size, with surprisingly little variation in the number of repeating units (degree of polymerization = 5). The polysaccharide is O-acetylated and contains a variety of O-methylated glycosyl residues, rendering the native glycan somewhat hydrophobic. The molecular mass of the major de-O-acetylated species, including the reducing end 3-deoxy-d-manno-2-octulosonic acid (Kdo) residue, is 3330 Da. The polysaccharide is comprised of a trisaccharide repeating unit having the structure -->4)-alpha-d-GlcpA-(1-->4)-[alpha-3-O-Me-6-deoxy-Talp-(1--> 3)]-alpha -l-Fucp-(1-->. The nonreducing end of the glycan is terminated with the capping sequence alpha-2,3, 4-tri-O-Me-Fucp-(1-->4)-alpha-d-GlcpA-(1-->, and the reducing end of the molecule consists of the non-repeating sequence -->3)-alpha-l-Fucp-(1-->3)-beta-d-Manp-(1-->3)-beta-QuiNA cp-(1-->4)-a lpha-Kdop-(2-->, where QuiNAc is N-acetylquinovosamine (2-N-acetamido-2,6-dideoxyglucose). The reducing end Kdo residue links the O-chain polysaccharide to the core region oligosaccharide, resulting in a unique location for a Kdo residue in LPS, removed four residues distally from the lipid A moiety. Structural heterogeneity in the O-chain arises mainly from the O-acetyl and O-methyl substitution. Methylation analysis using trideuteriomethyl iodide indicates that a portion of the 2,3,4-tri-O-methylfucosyl capping residues, typically 15%, are replaced with 2-O-methyl- and/or 2,3-di-O-methylfucosyl residues. In addition, approximately 25% of the 3,4-linked branching fucosyl residues and 10% of the 3-linked fucosyl residues are 2-O-methylated. A majority of the glucuronosyl residues are methyl-esterified at C-6. These unique structural features may be significant in the infection process.

Acetylation↗
PubMed2000

A close-up look at Io from Galileo's near-infrared mapping spectrometer.

Infrared spectral images of Jupiter's volcanic moon Io, acquired during the October and November 1999 and February 2000 flybys of the Galileo spacecraft, were used to study the thermal structure and sulfur dioxide distribution of active volcanoes. Loki Patera, the solar system's most powerful known volcano, exhibits large expanses of dark, cooling lava on its caldera floor. Prometheus, the site of long-lived plume activity, has two major areas of thermal emission, which support ideas of plume migration. Sulfur dioxide deposits were mapped at local scales and show a more complex relationship to surface colors than previously thought, indicating the presence of other sulfur compounds.

Extraterrestrial Environment↗
PubMed2000

Proximate humid and dry regions in Jupiter's atmosphere indicate complex local meteorology.

Models of Jupiter's formation and structure predict that its atmosphere is enriched in oxygen, relative to the Sun, and that consequently water clouds should be present globally near the 5-bar pressure level. Past attempts to confirm these predictions have led to contradictory results; in particular, the Galileo probe revealed a very dry atmosphere at the entry site, with no significant clouds at depths exceeding the 2-bar level. Although the entry site was known to be relatively cloud-free, the contrast between the observed local dryness and the expected global wetness was surprising. Here we analyse near-infrared (around 5 microm) observations of Jupiter, a spectral region that can reveal the water vapour abundance and vertical cloud structure in the troposphere. We find that humid and extremely dry regions exist in close proximity, and that some humid regions are spatially correlated with bright convective clouds extending from the deep water clouds to the visible atmosphere.

Atmosphere↗