Degradation of albumin in meningococcal sepsis Holland, Philip C; Hancock, Stephen W; Hodge, Donald ...
The Lancet (British edition),
06/2001, Letnik:
357, Številka:
9274
Journal Article
Recenzirano
We postulate that the proteolytic degradation of albumin into fragments could link the rapidity of the shock, rash, and hypocalcaemia associated with meningococcal sepsis. We examined urine of ...children with meningococcal disease and urine from control children with no sepsis and found albumin fragments of about 45 kDa, 25 kDa, and less than 20 kDa only in the urine of children with meningococcal sepsis and associated purpura. Exogenous or endogenous proteases, or both, may be released in severe meningococcal sepsis and, in association with an inadequate antiprotease response, result in albumin degradation. This may be a contributory factor to the rapid shock, hypocalcaemia, and rash seen in meningococcal sepsis.
(1) To develop a scale that is useful in evaluating the accuracy of multifrequency bioelectrical impedance analysis (MF-BIA) in the assessment of body water volumes against the accepted gold standard ...measurements based on isotope-dilution and total body potassium (TBK). (2) To perform a pilot test of the scale.
A scale was developed to evaluate the accuracy of MF-BIA in the assessment of body water volumes. Questions were obtained from reading the scientific literature and discussions involving the four authors. Three of these and two additional independent readers pre-tested the scale. A weighting was identified for each question and a pilot test with a sample of 10 articles (different to those used for the questionnaire performance) was conducted. A further validation was carried out with a second set of 20 articles and two additional independent readers.
The kappa statistic expressing the level of agreement between pairs of the first three authors using this scale with 10 articles, was 0.3, 0.4 and 0.6 after the first attempt. A second evaluation after specific changes improved the agreement to 0.8, 0.6 and 0.8. The mean score for 10 articles was 252+/-36 points from a total score of 400 (63+/-9%). The evaluation with the second set of 20 articles resulted in a kappa of 0.7 from two pairs of authors. The evaluation with two additional reviewers resulted in a kappa=0.7.
A tool has been developed to assess the accuracy of the MF-BIA technique and to identify methodological components, plan future studies and critically evaluate data in this area. It is likely that this tool may also be used to assess the accuracy of single frequency studies.
The crystal structure of recombinant human interleukin-1 beta (IL-1 beta) has been determined at 2.0 A resolution and refined to a crystallographic R-factor of 0.19. Three heavy-atom derivatives were ...identified and used for multiple isomorphous replacement phasing. Interpretation of the resulting electron density map revealed a structure in which there are 12 antiparallel beta-strands and no alpha-helix. The single 153-residue polypeptide chain is folded into a six-stranded beta-barrel similar in architecture to the Kunitz-type trypsin inhibitor found in soybeans. The molecule displays approximate 3-fold symmetry about the axis of the beta-barrel. Each successive pair of component strands of the barrel brackets an extensive sequence outside the barrel that includes an additional pair of beta-strands and a prominent loop. Together, these three external segments conceal much of the perimeter and one end of the barrel, leaving only the end supporting the chain termini fully exposed. The structure can be used to identify portions of the polypeptide chain that are exposed on the surface of the molecule, some of which must be epitopes recognized by interleukin-1 beta receptors.
Far-infrared Herschel images of the is an element of Eridani system, seen at a fifth of the Sun's present age, resolve two belts of debris emission. Fits to the 160 mu m PACS image yield radial spans ...for these belts of 12-16 and 54-68 AU. The south end of the outer belt is approximate to 10% brighter than the north end in the PACS+SPIRE images at 160, 250, and 350 mu m, indicating a pericenter glow attributable to a planet c From this asymmetry and an upper bound on the offset of the belt center, this second planet should be mildly eccentric (e(c) approximate to 0.03-0.3). Compared to the asteroid and Kuiper Belts of the young Sun, the is an element of Eri belts are intermediate in brightness and more similar to each other, with up to 20 km sized collisional fragments in the inner belt totaling approximate to 5% of an Earth mass. This reservoir may feed the hot dust close to the star and could send many impactors through the Habitable Zone, especially if it is being perturbed by the suspected planet is an element of Eri b, at semi-major axis approximate to 3 AU.
To assess the efficacy and safety of olanzapine/fluoxetine combination (OFC) for the acute treatment of bipolar depression in children and adolescents.
Patients 10 to 17 years of age with bipolar I ...disorder (BP-I), depressed episode, baseline Children’s Depression Rating Scale–Revised (CDRS-R) total score ≥40, Young Mania Rating Scale (YMRS) total score ≤15, and YMRS-item 1 ≤2 were randomized to OFC (6/25–12/50 mg/day olanzapine/fluoxetine; n = 170) or placebo (n = 85) for up to 8 weeks of double-blind treatment. The primary efficacy measure was mean change in CDRS-R using mixed-model repeated-measures methodology.
Baseline-to-week-8 least-squares mean change in CDRS-R total score was greater for OFC-treated patients than for placebo-treated patients (−28.4 versus −23.4, p = .003; effect size = .46), with between-group differences statistically significant at week 1 (p = .02) and all subsequent visits (all p < .01). Rates of and times to response and remission were statistically significantly greater for OFC- than for placebo-treated patients. The most frequent treatment-emergent adverse events in the OFC group were weight gain, increased appetite, and somnolence. Mean weight gain at patient’s endpoint was significantly greater for OFC- than for placebo-treated patients (4.4 kg versus 0.5 kg, p < .001). Treatment-emergent hyperlipidemia was very common among OFC-treated patients. Abnormal increases in hepatic analytes, prolactin, and corrected QT interval (QTc) were also common or very common but generally not clinically significant.
In this study, OFC was superior to placebo, and has been approved by the US Food and Drug Administration (FDA) for the acute treatment of bipolar I depression in patients 10 to 17 years of age. Benefits should be weighed against the risk of adverse events, particularly weight gain and hyperlipidemia.
Clinical trial registration information—A Study for Assessing Treatment of Patients Ages 10-17 with Bipolar Depression; http://clinicaltrials.gov; NCT00844857.
Hypervariable loops of HIV-1 Env protein gp120 are speculated to play roles in the conformational transition of Env to the receptor binding-induced metastable state. Structural analysis of ...full-length Env-based immunogens, containing the entire V2 loop, displayed tighter association between gp120 subunits, resulting in a smaller trimeric diameter than constructs lacking V2. A prominent basal quaternary location of V2 and V3' that challenges previous reports would facilitate gp41-independent gp120-gp120 interactions and suggests a quaternary mechanism of epitope occlusion facilitated by hypervariable loops. Deletion of V2 resulted in dramatic exposure of basal, membrane-proximal gp41 epitopes, consistent with its predicted basal location. The structural features of HIV-1 Env characterized here provide grounds for a paradigm shift in loop exposure and epitope occlusion, while providing substantive rationale for epitope display required for elicitation of broadly neutralizing antibodies, as well as substantiating previous pertinent literature disregarded in recent reports.
To study the complex formed between Tat protein and Env soluble trimeric immunogen, and compare with previously determined structures of Env native trimers and Env-CD4m complexes.
The soluble Env ...trimer was used to mimic the spike glycoprotein on the virus surface for the study. To overcome limitations of other structural determination methods, cryoelectron microscopy was employed to image the complex, and single particle reconstruction was utilized to reconstruct the structure of the complex from collected micrographs. Molecular modeling of gp120-Tat was performed to provide atomic coordinates for docking.
Images were preprocessed by multivariate statistical analysis to identify principal components of variation then submitted for reconstruction. Reconstructed structures were docked with modeled gp120-Tat atomic coordinates to study the positions of crucial epitopes.
Analysis of the Env-Tat complex demonstrated an intermediate structure between Env native trimers and Env-CD4m structures. Docking results indicate that the CD4-binding site and the V3 loop are exposed in the Env-Tat complex. The integrin-binding sequence in Tat was also exposed in Env-Tat docking.
The intermediate structure induced by Tat-interaction with Env could potentially provide an explanation for increased virus infection in the presence of Tat protein. Consequently, exposure of CD4-binding sites and a putative integrin-binding sequence on Tat in the complex may provide a new avenue for rational design of an effective HIV vaccine.
No molecular gas around nearby solar-type stars Greaves, J. S.; Coulson, I. M.; Holland, W. S.
Monthly notices of the Royal Astronomical Society,
02/2000, Letnik:
312, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Molecular gas around main-sequence stars is thought to disperse in only a few million years, constraining the time-scale for giant planets to form. However, this hypothesis has never been fully ...tested, as many of the search targets have been A-type stars, where the primary gas tracer, carbon monoxide, is readily photodissociated. A survey has been made of 14 nearby F and G stars with known circumstellar dust — no CO is detected, and a mean upper limit for all the stars implies less than 0.015 Uranus masses of H2. Since these solar-like stars have negligible dissociating UV radiation, this indicates that the lack of gas detections is not an observational bias, and also that theories with formation of the outer gas giants at late times are not supported.
Abstract
Recent Atacama Large Millimeter/submillimeter Array observations present mounting evidence for the presence of exocometary gas released within Kuiper Belt analogs around nearby main-sequence ...stars. This represents a unique opportunity to study their ice reservoir at the younger ages when volatile delivery to planets is most likely to occur. We here present the detection of CO
J
= 2-1 emission colocated with dust emission from the cometary belt in the 440 Myr old Fomalhaut system. Through spectrospatial filtering, we achieve a 5.4
σ
detection and determine that the ring’s sky-projected rotation axis matches that of the star. The CO mass derived (
) is the lowest of any circumstellar disk detected to date and must be of exocometary origin. Using a steady-state model, we estimate the CO+CO
2
mass fraction of exocomets around Fomalhaut to be between 4.6% and 76%, consistent with solar system comets and the two other belts known to host exocometary gas. This is the first indication of a similarity in cometary compositions across planetary systems that may be linked to their formation scenario and is consistent with direct interstellar medium inheritance. In addition, we find tentative evidence that
% of the detected flux originates from a region near the eccentric belt’s pericenter. If confirmed, the latter may be explained through a recent impact event or CO pericenter glow due to exocometary release within a steady-state collisional cascade. In the latter scenario, we show how the azimuthal dependence of the CO release rate leads to asymmetries in gas observations of eccentric exocometary belts.
Recent Atacama Large Millimeter/submillimeter Array observations present mounting evidence for the presence of exocometary gas released within Kuiper Belt analogs around nearby main-sequence stars. ...This represents a unique opportunity to study their ice reservoir at the younger ages when volatile delivery to planets is most likely to occur. We here present the detection of CO J = 2-1 emission colocated with dust emission from the cometary belt in the 440 Myr old Fomalhaut system. Through spectrospatial filtering, we achieve a 5.4σ detection and determine that the ring’s sky-projected rotation axis matches that of the star. The CO mass derived ((0.65--42)×10{sup −7} M{sub ⊕}) is the lowest of any circumstellar disk detected to date and must be of exocometary origin. Using a steady-state model, we estimate the CO+CO{sub 2} mass fraction of exocomets around Fomalhaut to be between 4.6% and 76%, consistent with solar system comets and the two other belts known to host exocometary gas. This is the first indication of a similarity in cometary compositions across planetary systems that may be linked to their formation scenario and is consistent with direct interstellar medium inheritance. In addition, we find tentative evidence that (49±27)% of the detected flux originates from a region near the eccentric belt’s pericenter. If confirmed, the latter may be explained through a recent impact event or CO pericenter glow due to exocometary release within a steady-state collisional cascade. In the latter scenario, we show how the azimuthal dependence of the CO release rate leads to asymmetries in gas observations of eccentric exocometary belts.
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