bluuebunny/crossref_metadata_2025_split huggingface dataset:
Following severe injury, hypocholesterolemia improves with convalescence but persists with organ failure or onset of infection
Authors: Dunham CMichael , Fealk Michael H , Sever Wilbur E 
Published: October 2003

Abstract
Introduction
Our primary objective was to determine the impact of traumatic injury, onset of infection, organ/metabolic dysfunction, and mortality on serum cholesterol.

Methods
During 676 surgical intensive care unit (SICU) days, 28 ventilated trauma patients underwent daily measurement of white blood cell (WBC) count and differential, cholesterol, arterial oxygen tension/fractional inspired oxygen, bilirubin, glucose, creatinine, and bicarbonate. With the onset of infection, WBC response was considered positive if the WBC count was 16.0 or greater, immature neutrophils were 10% or greater, or WBC count increased by 20%. Cholesterol response was considered positive if cholesterol decreased or failed to increase by 10%.

Results
Injury Severity Score was 30.6 ± 8.6 and there were 48 infections. Initial cholesterol was decreased (119 ± 44 mg/dl) compared with expected values from a database (201 ± 17 mg/dl; P < 0.0001). The 25 survivors had higher cholesterol at SICU discharge (143 ± 35 mg/dl) relative to admission (112 ± 37 mg/dl; P < 0.0001). In the three patients who died, the admission cholesterol was 175 ± 62 mg/dl and the cholesterol at death was 117 ± 27 mg/dl. The change in percentage of expected cholesterol (observed value divided by expected value) from admission to discharge was different for patients surviving (16 ± 19%) and dying (-29 ± 19%; P = 0.0005). With onset of infection, the WBC response was positive in 61% and cholesterol response was positive in 91% (P = 0.001). Percentage of expected cholesterol was decreased with each system dysfunction: arterial oxygen tension/fractional inspired oxygen < 350, creatinine > 2.0 mg/dl, glucose > 120 mg/dl, bilirubin > 2.5 mg/dl, and bicarbonate ≥ 28 or ≤ 23 (P < 0.01). Percentage of expected cholesterol decreased as the number of dysfunctions increased (P = 0.0001).

Conclusion
Hypocholesterolemia is seen following severe injury. Convalescing patients (ready for SICU discharge) have improved cholesterol levels, whereas dying patients appear to have progressive hypocholesterolemia. Decreasing or fixed cholesterol levels suggest the development of infection or organ/metabolic dysfunction. Cholesterol responses are more sensitive for the onset of infection than are WBC responses. Sequential cholesterol monitoring is recommended for patients with severe trauma.
CCL16/LEC powerfully triggers effector and antigen-presenting functions of macrophages and enhances T cell cytotoxicity
Authors: Cappello Paola , Caorsi Cristiana , Bosticardo Marita , De Angelis Stefania , Novelli Francesco , Forni Guido , Giovarelli Mirella 
Published: October 2003

AbstractThe huan CC chemokine CCL16, a liver-expressed chemokine, enhances the killing activity of mouse peritoneal macrophages by triggering their expression of tumor necrosis factor α (TNF-α) and Fas ligand. Macrophages also respond to CCL16 by enhancing their production of monocyte chemoattractant protein-1, regulated on activation, normal T cells expressed and secreted chemokines, and interleukin (IL)-1β, TNF-α, and IL-12. The effect of CCL16 is almost as strong as that of lipopolysaccharide and interferon-γ, two of the best macrophage activators. Moreover, CCL16-activated macrophages overexpress membrane CD80, CD86, and CD40 costimulatory molecules and extensively phagocytose tumor cell debris. On exposure to such debris, they activate a strong, tumor-specific, cytolytic response in virgin T cells. Furthermore, cytolytic T cells generated in the presence of CCL16 display a higher cytotoxicity and activate caspase-8 in tumor target cells. This ability to activate caspase-8 depends on their overexpression of TNF-α and Fas ligand induced by CCL16. These data reveal a new function for CCL16 in the immune-response scenario. CCL16 significantly enhances the effector and the antigen-presenting function of macrophages and augments T cell lytic activity.
The interaction of human dendritic cells with yeast and germ-tube forms ofCandida albicansleads to efficient fungal processing, dendritic cell maturation, and acquisition of a Th1 response-promoting function
Authors: Romagnoli G , Nisini R , Chiani P , Mariotti S , Teloni R , Cassone A , Torosantucci A 
Published: October 2003

AbstractT helper cell type 1 (Th1) cell-mediated immunity plays a rical role in protection against the opportunistic pathogen Candida albicans. Virulence of the fungus is closely associated with its ability to form germ-tubes (GT), the early phase of the dimorphic transition from the commensal yeast (Y) to the more invasive hyphal (H) form. In this study, we examined the functional outcome of the interaction of Y or GT forms with human dendritic cells (DCs), professional antigen-presenting cells, which are pivotal for initiation and modulation of T cell responses. DCs phagocytosed and killed Y and GT cells with a comparable efficiency, becoming able to trigger strong proliferative responses by Candida-specific, autologous T cell clones. Both fungal forms induced DC maturation, as indicated by up-regulation of CD83, CD80, CD86, CD40, and major histocompatibility complex classes I and II surface antigens. Chemokine receptors were also modulated in Candida–DCs, which showed increased CCR7/CXCR4 and decreased CCR5 expression. Y- and GT-activated DCs differed in the pattern of cytokine expression. In particular, GT cells, in common with fully differentiated H cells, induced significantly more elevated levels of interleukin (IL)-10 than Y cells. Nevertheless, Y-, GT-, or H-pulsed DCs secreted comparable amounts of IL-12p70. In addition, irrespective of the fungal form triggering DC activation, Candida–DCs acquired the ability to prime naive T lymphocytes with a defined Th1 phenotype. Overall, our findings highlight the induction of substantially similar functional patterns in human DCs encountering the different forms of growth of C. albicans, both seemingly activating the Th1-type immunity which is characteristic of the healthy human subjects, naturally immunized and protected against the fungus.
Injury, sepsis, and the regulation of Toll-like receptor responses
Authors: Murphy Thomas J , Paterson Hugh M , Mannick John A , Lederer James A 
Published: October 2003

AbstractAlthough we tend to think that the immune system has evolved to protect the host from invading pathogens and to discriminate between self and nonself, there must also be an element of the immune system that has evolved to control the response to tissue injury. Moreover, these potential immune-regulatory pathways controlling the injury response have likely coevolved in concert with self and nonself discriminatory immune-regulatory networks with a similar level of complexity. From a clinical perspective, severe injury upsets normal immune function and can predispose the injured patient to developing life-threatening infectious complications. This remains a significant health care problem that has driven decades of basic and clinical research aimed at defining the functional effects of injury on the immune system. This review and update on our ongoing research efforts addressing the immunological response to injury will highlight some of the most recent advances in our understanding of the impact that severe injury has on the innate and adaptive immune system focusing on phenotypic changes in innate immune cell responses to Toll-like receptor stimulation.
Expression and regulation of antimicrobial peptides in the gastrointestinal tract
Authors: Cunliffe R N , Mahida Y R 
Published: October 2003

AbstractThe gastrointestinal (GI) tract is exposed to a wide range of microorganisms. The expression of antimicrobial peptides has been demonstrated in different regions of the GI tract, predominantly in epithelial cells, which represent the first host cells with which the microorganisms have to interact for invasion. The intestinal epithelial monolayer is complex, consisting of different cell types, and most have a limited lifespan. Of the GI antimicrobial peptides, α- and β-defensins have been studied the most and are expressed by distinct types of epithelial cells. Enteric α-defensin expression is normally restricted to Paneth and intermediate cells in the small intestine. However, there are important differences between mice and humans in the processing of the precursor forms of enteric α-defensins. Parasite infection induces an increase in the number of enteric α-defensin-expressing Paneth and intermediate cells in the murine small intestine. In the chronically inflamed colonic mucosa, metaplastic Paneth cells (which are absent in the normal colon) also express enteric α-defensins. Epithelial expression of β-defensins may be constitutive or nducible by infectious and inflammatory stimuli. The production of some members of the β-defensin family appears to be restricted to distinct parts of the GI tract. Recent studies using genetically manipulated rodents have demonstrated the likely in vivo importance of enteric antimicrobial peptides in innate host defense against microorganisms. The ability of these peptides to act as chemoattractants for cells of the innate- and adaptive-immune system may also play an important role in perpetuating chronic inflammation in the GI tract.
Interferon-γ: an overview of signals, mechanisms and functions
Authors: Schroder Kate , Hertzog Paul J , Ravasi Timothy , Hume David A 
Published: October 2003

AbstractInterferon-γ (IFN-γ) coordinates a diverse array of cellular programs through transcriptional regulation of immunologically relevant genes. This article reviews the current understanding of IFN-γ ligand, receptor, ignal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophage function during infection. The current model for IFN-γ signal transduction is discussed, as well as signal regulation and factors conferring signal specificity. Cellular effects of IFN-γ are described, including up-regulation of pathogen recognition, antigen processing and presentation, the antiviral state, inhibition of cellular proliferation and effects on apoptosis, activation of microbicidal effector functions, immunomodulation, and leukocyte trafficking. In addition, integration of signaling and response with other cytokines and pathogen-associated molecular patterns, such as tumor necrosis factor-α, interleukin-4, type I IFNs, and lipopolysaccharide are discussed.
Activation of A2A adenosine receptors inhibits expression of α4/β1 integrin (very late antigen-4) on stimulated human neutrophils
Authors: Sullivan Gail W , Lee David D , Ross William G , DiVietro Jeffrey A , Lappas Courtney M , Lawrence Michael B , Linden Joel 
Published: October 2003

AbstractThe α4/β1 integrin very late antigen-4 (CD49d/CD29) is up-regulated on circulating neutrophils of septic patients. Although no individual agent mimics this effect of sepsis, we now report that following priming of human neutrophils with lipopolysaccharide or tumor necrosis factor α (TNF-α), addition of formyl-Met-Leu-Phe (fMLP) results in a “stimulated”, sepsis-like, four- to fivefold rise in CD49d expression. TNF/fMLP stimulation also produced a similar increase in CD49d-mediated adhesion of neutrophils to a vascular cell adhesion molecule-1 (VCAM-1)-coated surface. Adenosine is a naturally occurring, anti-inflammatory mediator released from injured or inflamed tissues. We observed that stimulated neutrophil CD49d expression was decreased by activation of A2A adenosine receptors (A2AAR) with the selective agonist 4-{3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylicacid methyl ester (ATL146e; EC50=6.4 nM). ATL146e (100 nM) also reduced the fraction of stimulated neutrophils that adhered to VCAM-1 from 38 ± 6% to 27 ± 5%. Inhibition of CD49d expression was equally inhibited by ATL146e, added before or after TNF priming, and was reversed by incubation with the A2AAR-selective antagonist 4-{2-[7-amino-2-(2-furyl) (1, 2, 4)triazolo(2,3-a) (1, 3, 5)triazin-5-yl-amino]ethyl}-phenol (ZM241385; 100 nM). A suboptimal ATL146e concentration (1 nM) combined with the type IV phosphodiesterase inhibitor rolipram (100 nM) synergistically decreased stimulated CD49d expression by &gt;50%. The cyclic adenosine monophosphate (cAMP)-dependent kinase [protein kinase A (PKA)] inhibitor H-89 (10 μM) reversed the effect of ATL146e on stimulated CD49d expression. Other means of increasing cAMP in neutrophils also decreased stimulated CD49d expression. We conclude that adenosine binding to A2AAR counteracts stimulation of neutrophil CD49d integrin expression and neutrophil binding to VCAM-1 via a cAMP/PKA-mediated pathway.
Subset-specific, uniform activation among Vγ6/Vδ1+ γδ T cells elicited by inflammation
Authors: Roark Christina L , Aydintug M Kemal , Lewis Julie , Yin Xiang , Lahn Michael , Hahn Youn-Soo , Born Willi K , Tigelaar Robert E , O’Brien Rebecca L 
Published: October 2003

AbstractThe Vγ6/Vδ1+ cells, the second murine γδ T cell subset to arise in the thymus, express a nearly invariant T cell receptor (TCR), colonize select tissues, and expand preferentially in other tissues during inflammation. These cells are thought to help in regulating the inflammatory response. Until now, Vγ6/Vδ1+ cells have only been detectable indirectly, by expression of Vγ6-encoding mRNA. Here, we report that 17D1, a monoclonal antibody, which detects the related epidermis-associated Vγ5/Vδ1+ TCR, will also bind the Vγ6/Vδ1+ cells if their TCR is first complexed to an anti-Cδ antibody. Features of this special condition for recognition suggest the possibility that an alternate structure exists for the Vγ6/Vδ1 TCR, which is stabilized upon binding to the anti-Cδ antibody. Using the 17D1 antibody as means to track this γδ T cell subset by flow cytometry, we discovered that the response of Vγ6/Vδ1+ cells during inflammation often far exceeds that of other subsets and that the responding Vγ6/Vδ1+ cells display a strikingly uniform activation/memory phenotype compared with other γδ T cell subsets.
In vitro model for hematopoietic progenitor cell homing reveals endothelial heparan sulfate proteoglycans as direct adhesive ligands
Authors: Netelenbos Tanja , van den Born Jacob , Kessler Floortje L , Zweegman Sonja , Huijgens Peter C , Dräger Angelika M 
Published: October 2003

AbstractProteoglycans (PGs) play a dominant role within the bone marrow (BM), but their role in homing of transplanted hematopoietic progenitor cells (HPC) is unknown. In this study, the role of heparan sulfate (HS) PGs on BM endothelium as adhesive structures was investigated. HPC (primary CD34+ cells and cell line KG-1a) were able to bind fractionated heparin, which could be competed by highly sulfated heparin/HS-glycosaminoglycans (GAGs). Under flow conditions, HPC adhered to immobilized heparin after rolling over E-selectin. Rolling of KG-1a on BM endothelial cell (EC) line 4LHBMEC was completely E selectin-dependent. Addition of heparin/HS-GAGs, endothelial treatment with chlorate, or anti-HS all partially inhibited firm adhesion. Moreover, enzymatic removal of endothelial HS-GAGs reduced initial adhesion. Finally, HPC-bound PGs isolated from 4LHBMEC, which was largely inhibited by enzymatic HS-degradation. In summary, we identified sulfated structures on BM endothelium, most likely HSPGs, as a novel class of glycoconjugates involved in the multistep homing cascade of HPC.
Antiequine Chorionic Gonadotropin (eCG) Antibodies Generated in Goats Treated with eCG for the Induction of Ovulation Modulate the Luteinizing Hormone and Follicle-Stimulating Hormone Bioactivities of eCG Differently
Authors: Hervé Virginie , Roy François , Bertin Jean , Guillou Florian , Maurel Marie-Christine 
Published: October 2003

AbstractIn dairy goats, treatments associating a progestogen and the equine chorionic gonadotropin (eCG) are the easiest way to induce and synchronize estrus and ovulation and to permit artificial insemination (AI) and/or out of season breeding. From the first treatment, the injection of eCG induces, in some females, the production of anti-eCG antibodies (Abs) that will interfere with the effectiveness of subsequent treatments. These anti-eCG Abs delay the preovulatory LH surge and the ovulation time, leading to poor fertility of the treated females. In this study, by in vitro bioassays, we show that anti-eCG Abs can positively or negatively modulate the LH and/or FSH bioactivities of eCG. Moreover, the modulation level of eCG bioactivity does not depend on the anti-eCG Ab affinity for eCG, as shown by surface plasmon resonance technology. The specificity of anti-eCG Abs tested by competitive ELISA highlighted the importance of a glycan environment in the recognition mechanism, especially the sialic acids specific to eCG. The different effects of anti-eCG Abs on eCG bioactivities could be explained by two hypotheses. First, steric hindrance preventing the interaction of eCG with its receptors would explain the inhibitory effect of some anti-eCG Abs; second, a conformational change in eCG by anti-eCG Abs could induce inhibition or potentiation of eCG bioactivities. It is significant that these modulations of eCG bioactivities by anti-eCG Abs impact mainly on the FSH bioactivity of eCG, which is essential for ovarian stimulation and subsequent fertility after treatment and AI, and to a lesser extent on LH bioactivity.
The Volume of a Sexually Dimorphic Nucleus in the Ovine Medial Preoptic Area/Anterior Hypothalamus Varies with Sexual Partner Preference
Authors: Roselli Charles E. , Larkin Kay , Resko John A. , Stellflug John N. , Stormshak Fred 
Published: October 2003

AbstractSheep are one of the few animal models in which natural variations in male sexual preferences have been studied experimentally. Approximately 8% of rams exhibit sexual preferences for male partners (male-oriented rams) in contrast to most rams, which prefer female partners (female-oriented rams). We identified a cell group within the medial preoptic area/anterior hypothalamus of age-matched adult sheep that was significantly larger in adult rams than in ewes. This cell group was labeled the ovine sexually dimorphic nucleus (oSDN). In addition to a sex difference, we found that the volume of the oSDN was two times greater in female-oriented rams than in male-oriented rams. The dense cluster of neurons that comprise the oSDN express cytochrome P450 aromatase. Aromatase mRNA levels in the oSDN were significantly greater in female-oriented rams than in ewes, whereas male-oriented rams exhibited intermediate levels of expression. Because the medial preoptic area/anterior hypothalamus is known to control the expression of male sexual behaviors, these results suggest that naturally occurring variations in sexual partner preferences may be related to differences in brain anatomy and capacity for estrogen synthesis.
Activins Are Critical Modulators of Growth and Survival
Authors: Brown Chester W. , Li Liunan , Houston-Hawkins Dianne E. , Matzuk Martin M. 
Published: October 2003

AbstractActivins βA and βB (encoded by Inhba and Inhbb genes, respectively) are related members of the TGF-β superfamily. Previously, we generated mice with an Inhba knock-in allele (InhbaBK) that directs the expression of activin βB protein in the spatiotemporal pattern of activin βA. These mice were small and had shortened life spans, both influenced by the dose of the hypomorphic InhbaBK allele. To understand the mechanism(s) underlying these abnormalities, we now examine growth plates, liver, and kidney and analyze IGF-I, GH, and major urinary proteins. Our studies show that activins modulate the biological effects of IGF-I without substantial effects on GH, and that activin signaling deficiency also has modest effects on hepatic and renal function. To assess the relative influences of activin βA and activin βB, we produced mice that express activin βB from the InhbaBK allele, and not from its endogenous Inhbb locus. InhbaBK/BK, Inhbb−/− mice have failure of eyelid fusion at birth and demonstrate more severe effects on somatic growth and survival than either of the corresponding single homozygous mutants, showing that somatic growth and life span are supported by both activins βA and βB, although activin βA plays a more substantial role.
Evidence for lymphatic transport of insulin by topically applied biphasic vesicles
Authors: King Martin J , Michel Deborah , Foldvari Marianna 
Published: October 2003

AbstractThe cutaneous delivery pathway through the lymphatics of a novel transdermal lipid-based delivery system (biphasic vesicles), which was previously shown to deliver sustained physiological levels of basal insulin in a pain-free manner across the skin, was evaluated in a diabetic rat model. Transdermal patches (one per rat) containing insulin in biphasic vesicles (1–10 mg recombinant human insulin dose) were applied to the shaved abdominal skin of streptozotocin-induced diabetic rats for 73 h. Blood glucose was monitored approximately every 2–10 h using a Lifescan glucose meter. Inguinal lymph node insulin levels were analysed by ELISA. Insulin in the lymph nodes increased in a dose- and time-dependent manner. Maximal transdermal insulin concentrations in the lymph nodes were observed with both 140 IU (5 mg: 43.0 + 18.0 μIU mg−1 (mean + s.e.m., n = 4)) and 280 IU (10 mg: 48.0 + 19.6 μIU mg−1 (mean + s.e.m., n = 4)) doses of recombinant insulin at t = 73 h. The level of insulin in the lymph nodes after subcutaneous injection of 1 mg insulin at the peak blood glucose response was 35.8 μIU mg−1 (n = 2), before falling to 0.35 μIU mg−1 by t = 48 h (n = 2). The lymphatics is involved in the transdermal insulin delivery by biphasic vesicles. This is the first report on the lymphatic transport of a protein after non-invasive topical application on the skin.
Simulation of heat transfer during rotational molding
Authors: Greco A. , Maffezzoli A. , Vlachopoulos J. 
Published: October 2003

AbstractIn rotational molding, polymer powders are subjected to heating, melting, cooling, and subsequent solidification in biaxially rotating molds. Heat transfer phenomena during rotational molding are significantly affected by the presence of endothermic and exothermic transitions. In this paper instead of using the traditional moving interface method, a new approach is presented which is applicable to semicrystalline materials like linear low‐density polyethylene. Melting is described by a statistical model and crystallization by a kinetic model. The model parameters are determined from differential scanning calorimetry measurements. The one‐dimensional unsteady heat conduction equation is solved by a finite difference method. The numerical predictions are in good agreement with experimental data. The overall heat transfer model can be used for process optimization purposes. © 2003 Wiley Periodicals, Inc. Adv Polym Techn 22: 271–279, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.10055