Infections in the elderly, similar to other acute illnesses in this age group, may present in atypical, nonclassical fashions. Fever, the cardinal sign of infection, may be absent or blunted 20%-30% of the time. An absent or blunted fever response may in turn contribute to diagnostic delays in this population, which is already at risk for increased morbidity and mortality due to infection. On the other hand, the presence of a fever in the geriatric patient is more likely to be associated with a serious viral or bacterial infection than is fever in a younger patient. Finally, a diagnosis can be made in the majority of cases of fever of unknown origin (FUO) in the elderly. FUO is often associated with treatable conditions in this age group.
Key Points• ATX stored in a-granules of resting platelets is secreted upon tumor cell-induced aggregation leading to prometastatic LPA production.• Nontumoral ATX promotes early bone colonization by breast cancer cells and contributes to the progression of skeletal metastases.Autotaxin (ATX), through its lysophospholipase D activity controls physiological levels of lysophosphatidic acid (LPA) in blood. ATX is overexpressed in multiple types of cancers, and together with LPA generated during platelet activation promotes skeletal metastasis of breast cancer. However, the pathophysiological sequelae of regulated interactions between circulating LPA, ATX, and platelets remain undefined in cancer. In this study, we show that ATX is stored in a-granules of resting human platelets and released upon tumor cell-induced platelet aggregation, leading to the production of LPA.
Thrombin-induced platelet microbicidal protein (PMP) is considered to play an important role in preventing streptococcal endocarditis. However, the structural features and functions of PMPs have not been well characterized, and their antibacterial spectra against other common endocarditis pathogens, such as the staphylococci, are not known. Thrombin stimulation of washed rabbit platelets (108/ml) yielded a PMP-rich preparation with a specific activity of-25 U/mg of protein as determined by Bacilus subtilis bioassay. TIwenty-eight clinical and laboratory Staphylococcus aureus isolates, exposed to a standardized PMP preparation (100 U/ml for 2 h at 37°C), exhibited a Poisson-distributed heterogeneity to the bactericidal action of PMP, with approximately one-third designated as PMP resistant. Gel filtration chromatography (Sephadex G-50) identified the bioactive moiety within PMP preparations to be in the major protein elution peak; sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) presumptively identified PMP as a lowmolecular-weight (MW) (8,500) protein present only in such bioactive protein peaks. Both the bioactivity of PMP preparations and the low-MW protein band were removable by specific anionic membranes (e.g., cellulose-acetate/nitrate), as well as by a variety of anionic resins, further corroborating the suspected cationic charge of PMP. In addition, both PMP bioactivity and the low-MW protein band were recoverable by 1.5 M NaCl elution of the anionic membrane filters post-PMP adsorptive removal. Adsorption of bioactive PMP preparations by highly PMP-susceptible B. subtilis (10' CFU/ml, 30 min) resulted in a near-complete loss of residual bioactivity; in contrast, adsorption of bioactive PMP preparations with less PMP-susceptible S. aureus strains failed to reduce bioactivity. Significant lysozyme contamination of PMP-rich preparations was ruled out by determination of differences between bioactive PMP preparations and exogenous lysozyme as regards (i) relative heat stabilities; (ii) differential bactericidal activity versus B. subtilis and Micrococcus luteus; and (iii) SDS-PAGE protein profiles. These data show that the bioactive PMP protein moiety is of low MW, is heat stable, is probably cationic (similar to leukocyte-derived defensins), and possesses potent bactericidal activity against a significant percentage of S. aureus isolates. * Corresponding author. termed thrombodefensins (5); however, their exact relationship to other defensin molecules, such as the leukocyte defensins (12), has not been defined. Thrombin-induced PMP(s) remain poorly characterized, and their structure, function, and microbicidal pathways have not been fully determined. In the present study, we describe the preparation, partial purification, and initial characterization of thrombin-induced PMP. In addition, we utilized Staphylococcus aureus, the most common etiologic agent of intravascular infections (19), to probe the functional microbicidal features of PMP. (A portion of this study was presented at the gen...
Objective To test the hypothesis that many nursing home residents with an apparently blunted fever response (maximum temperature
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