Prevalence and clinical significance of fever in acute exacerbations of chronic obstructive pulmonary disease.

Fever is an important, although not always present, sign in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The objective of this study was to determine the prevalence of fever and its clinical significance in these episodes. Two hundred seventeen AECOPD hospitalizations were included in a prospective study and were categorized as febrile (FH) or afebrile (AFH), using as a cutoff a rectal temperature measurement of 37.8 degrees C during hospitalization. Eighty-six hospitalizations (39.6%) were identified as AFH. The patients in this group had significantly more severe airway obstruction and hypoxemia, a higher rate of chronic obstructive pulmonary disease (COPD) complications, a higher rate of type 3 exacerbation, a shorter length of hospitalization and a higher rate of readmissions than patients in the FH group. The results of this study show that more than one-third of AECOPD hospitalizations are attributable to afebrile episodes. These episodes are characterized by lower rates of bronchitis manifestations in patients with more severe disease. Although the length of hospitalization for these episodes is shorter, the readmission rate is higher.

Serological evidence of acute infection with the Chlamydia-like microorganism Simkania negevensis (Z) in acute exacerbation of chronic obstructive pulmonary disease.

The aims of this study were twofold: (i) to test for possible associations between serological evidence of acute Simkania negevensis (Sn) infection and acute exacerbation of chronic obstructive pulmonary disease and (ii) to examine the prevalence of past infections with Sn in patients with chronic obstructive pulmonary disease. In 120 patients (63%) there was serological evidence of past infection with Sn, which was not significantly different from the rate in a control population. In five hospitalizations serological evidence existed of acute infection with Sn around the time of the exacerbation of chronic obstructive pulmonary disease. In four of these cases, there was serological evidence of acute infection with at least one other respiratory pathogen. It is concluded that Sn can be associated serologically with exacerbation of chronic obstructive pulmonary disease, in most cases together with other respiratory pathogens. The implications of these findings should be investigated further.

Allosteric interactions between DNA strands and monovalent cations in DNA quadruplex assembly: thermodynamic evidence for three linked association pathways.

The series of cooperative transitions that lead to [d(TG4)4.(K+)m] quadruplex assembly upon rapid addition of KCl to d(TG4) strands were studied. Quadruplex samples were dialyzed against KCl then Li-EDTA and found to retain between three and five strongly bound potassiums with affinities >10(6) M-2. Absorbance thermal denaturation (melt) and circular dichroism (CD) equilibrium binding data were obtained. The latter were analyzed using two classes of binding models to simulate the effects of the assumed intermolecular interactions on the binding curves (isotherms). The melt experiments yielded equilibrium dissociation constants (Kd) ranging from 10(-11) to 10(-12) M3 at the melting temperatures. Extrapolating these values to 23 degrees C predicts Kd values in the 10(-28) M3 range if the heat capacity (Cp) is not strongly dependent upon temperature changes over this range. Assuming Ka is equal to 1/Kd (from melting analyses), very large association free energies stabilize the quadruplex at 23 degrees C in 100 mM KCl (DeltaGa = -43 kcal mol-1). Plots of the differential melt curve peak half-widths, a measure of cooperativity, versus d(TG4) concentration showed that quadruplex dissociation is much more cooperative at 400 mM KCl than at 100 mM KCl. Forty-eight hour quadruplex assembly time courses were monitored by CD at 264 nm. Equilibrium quadruplex accumulation generally required over 10 h, and net reaction extents were in the 10-85% range. Hill plots of the data show that initial steps in the multistep pathway are positively cooperative, presumably due to strong strand-cation and strand-strand binding interactions in duplex and triplex assembly reactions, then negatively cooperative in quadruplex formation. Models were developed to rationalize the experimental observations in terms of consecutive cooperative allosteric transitions from cation-deficient relaxed (R) strand-aggregates to cation-containing tense (T) structures, driven by the allosteric effector K+. Quantitative mappings of positive and then negative cooperativity were obtained by fitting the results as a function of strand number incorporated during quadruplex assembly. Surprisingly, models for reactions involving incorporation of five and six strands fit the data better than models involving only four strands. The 5-step "induced fit" model fits the data as well as or better than 3- and 4-step models and better than all of the strand aggregation models that were devised and investigated. Net association free energies (summation operatori=1,n) ranged from -20 to -26 kcal mol-1, approximately half the magnitude of the apparent stabilities measured by absorbance melts. Likely explanations for this discrepancy involve hysteresis and errors due to inadequate equilibration in the melt experiments. Hysteresis is thought to be produced by irreversibility due to different predominant mechanisms in absorbance (dissociation) and CD (association) experiments. The kinetic block to quadruplex assembly can be unambiguously attributed to quadruplex formation and not intermediate steps in the assembly mechanism. On the basis of these results we propose that, in addition to the more conventional assembly mechanisms involving duplex dimerization and stepwise strand addition, quadruplex formation can also proceed by triplex-triplex disproportionation. Interaction statistics arguments that support the energetic feasibility of the disproportionation pathway are presented. The allosteric quadruplex assembly model provides a mechanism which could be used by the cell to simultaneously modulate DNA structure and activity within telomeres, transcriptional promoters, recombination-prone chromatin, and other G-rich DNAs. As a result of this allosterism, cation and strand availability and strand-pairing capabilities could profoundly influence the functional capacity of a particular strand over a relatively narrow range of effector concentration changes. (ABSTRACT TRUNCATED)

Factors affecting activation of the 'cloaked' Zea maize ribosome inactivating protein (RIP) zymogen. 1. 'LID' peptide hydrophobicities and oxidative structural changes.

We want to understand how environmental factors influence zymogen activation of the "cloaked' active site of the 'Ribosome Inactivating Protein' (RIP) from corn kernels. In this study, we focus on how likely chemical effectors in the immediate environment of the 'lid' conspire to unleash the active site upon encountering target membranes of invading pests. Octanol-H2O partitioning free energies of peptides which (i) straddle the proteolysis site, and (ii) form the 'side' and 'bottom' of the proposed 'lid' were found to only slightly favor H2O, suggesting that the peptide is poised to detach from the less polar surface surrounding the RIP active site. Circular dichroism results obtained upon catalase/H2O2 oxidation of the 'lid' peptide suggest that the structure shifts from primarily alpha-helical to primarily beta-like. These results suggest that the active site is more easily 'uncloaked' as a result of the lowered solvent polarity conditions and higher oxidant concentrations in the presence of pest membranes encountered during crucial stages of seed germination.