Publications by authors named "ZIMMERMAN G"

The mechanisms by which neutrophils, key effector cells of the innate immune system, express new gene products in inflammation are largely uncharacterized. We found that they rapidly translate constitutive mRNAs when activated, a previously unrecognized response. One of the proteins synthesized without a requirement for transcription is the soluble IL-6 receptor alpha, which translocates to endothelial cells and induces a temporal switch to mononuclear leukocyte recruitment.

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Purpose: The purpose of this pilot study was to compare disability self-assessment and upper quarter muscle balance female dental hygienists and non dental hygienist females. The upper quarter was operationally defined as the shoulder and neck region. Muscle balance was operationally defined as muscle flexibility and muscle performance.

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Platelet-activating factor (PAF) is a potent proinflammatory phospholipid with diverse pathological and physiological effects. This bioactive phospholipid mediates processes as diverse as wound healing, physiological inflammation, apoptosis, angiogenesis, reproduction and long-term potentiation. Recent progress has demonstrated the participation of MAP kinase signaling pathways as modulators of the two critical enzymes, phospholipase A2 and acetyltransferase, involved in the remodeling pathway of PAF biosynthesis.

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Platelets are small in size and simple in structure. Nevertheless, these anucleate cytoplasts utilize complex molecular systems to regulate a variety of biological functions. Here we review evolutionary paths, traditional roles, and previously unrecognized biological capacities of platelets that interface thrombosis with inflammation and potentially identify new roles in inflammatory diseases.

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The reversible airway hyper-reactivity (AHR) of asthma is modeled by sensitizing and challenging mice with aerosolized ovalbumin. However, the C57BL/6 murine strain does not display the large increase in circulating IgG and IgE antibodies found in human atopy and asthma. We found that commercial ovalbumin was contaminated with lipopolysaccharide (LPS) in amounts sufficient to fully activate endothelial cells in an in vitro assay of the first step of inflammation.

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Oxidized low density lipoprotein (LDL) has an important proinflammatory role in atherogenesis. In this study, we investigated the ability of oxidized LDL (oxLDL) and its phospholipid components to induce lipid body formation in leukocytes. Incubation of mouse peritoneal macrophages with oxidized, but not with native LDL led to lipid body formation within 1 h.

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The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in inflammatory states, and COX-2 overexpression plays a key role in carcinogenesis. To understand the mechanisms regulating COX-2 expression, we examined its posttranscriptional regulation mediated through the AU-rich element (ARE) within the COX-2 mRNA 3'-untranslated region (3'UTR). RNA binding studies, performed to identify ARE-binding regulatory factors, demonstrated binding of the translational repressor protein TIA-1 to COX-2 mRNA.

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Plasma platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase that inactivates platelet-activating factor (PAF) and PAF-like lipids to generate products with little or no biological activity. The levels of circulating PAF-AH correlate with several disease syndromes. We previously reported that mediators of inflammation regulate the expression of the human PAF-AH gene at the transcriptional level.

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Lipopolysaccharides and triacyl-cysteine-modified proteins of Gram-negative and positive organisms are potent endotoxins. Animal models show that the receptor for platelet-activating factor (PAF) is responsible for many of the deleterious effects of endotoxin, where regulated, localized PAF production localizes the inflammatory response. In contrast, biologically active analogs of PAF (PAF-like lipids) are generated by oxidative attack on phospholipids by chemical reactions that are unregulated and unlocalized.

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Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are syndromes of acute respiratory failure that result from acute pulmonary edema and inflammation. The development of ALI/ARDS is associated with several clinical disorders including direct pulmonary injury from pneumonia and aspiration as well as indirect pulmonary injury from trauma, sepsis, and other disorders such as acute pancreatitis and drug overdose. Although mortality from ALI/ARDS has decreased in the last decade, it remains high.

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Objective: Platelet-activating factor (PAF) is a proinflammatory phospholipid that may contribute to inflammation in the acute respiratory distress syndrome (ARDS). PAF acetylhydrolase (PAF-AH) degrades PAF and regulates its biological activity. We characterized PAF-AH in bronchoalveolar lavage fluid from ARDS patients (n = 33, 22 survivors), patients at risk for ARDS (n = 6), and healthy controls (n = 6).

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Interactions of leukocytes with endothelial cells are early events in acute and chronic inflammation, immune surveillance of tissues, and wound defense and repair. In contrast with their requisite roles in host defense, dysregulated leukocyte-endothelial interactions mediate inflammatory tissue injury, thrombosis, and other pathologic sequelae. Recent observations also identify dysregulated leukocyte-endothelial interactions in neoplasia and sickle cell vasculopathy.

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Objective: The purpose of this study was to determine the mechanism with which fluid flow inhibits endothelial E-selectin expression.

Methods: Cultured human umbilical vein endothelial cells were stimulated with inflammatory agonists (tumor necrosis factor-alpha [TNF-alpha], interleukin-1beta, oncostatin M, or phorbol ester) in the presence or absence of fluid flow (peak shear stress, approximately 12 dynes/cm(2)) imposed with an orbital shaker. E-selectin expression was assessed with ribonuclease protection assay, immunoblotting, enzyme-linked immunosorbent assay, or metabolic labeling as appropriate.

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Lysophosphatidic acid (LPA) is a pluripotent lipid mediator acting through plasma membrane-associated LPA(x) receptors that transduce many, but not all, of its effects. We identify peroxisome proliferator-activated receptor gamma (PPARgamma) as an intracellular receptor for LPA. The transcription factor PPARgamma is activated by several lipid ligands, but agonists derived from physiologic signaling pathways are unknown.

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Paraoxonase-1 (PON1), an high density lipoprotein (HDL)-associated organophosphate triesterase, suppresses atherosclerosis in an unknown way. Purified PON1 protects lipoprotein particles from oxidative modification and hydrolyzes pro-atherogenic oxidized phospholipids and the inflammatory mediator platelet-activating factor (PAF). We find human PON1 acted as a phospholipase A(2) but not as a phospholipase C or D through cleavage of phosphodiester bonds as expected.

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The components of inflammation, including macrophages, cytokines and lipid inflammatory mediators, have a role in atherosclerosis. A key lipid mediator in regulated, physiologic inflammation is platelet-activating factor (PAF). PAF activates cells, including monocytes, through a single molecularly characterized receptor, the PAF receptor (PAFR), at exceedingly low concentrations.

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Apoptosis mediated by Fas/Fas ligand (FasL) interaction has been implicated in human disease processes, including pulmonary disorders. However, the role of the Fas/FasL system in acute lung injury (ALI) and in the acute respiratory distress syndrome (ARDS) is poorly defined. Accordingly, we investigated both the soluble and cellular expression of the Fas/FasL system in patients with ALI or ARDS.

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Background: Utilizing donor hearts with prolonged graft ischemia may extend the donor pool.

Methods And Results: The medical records of 363 infants and children, aged 1 day to 17 years, transplanted at Loma Linda University between November 1985 and March 2001, were retrospectively reviewed. Fourteen children received organs with prolonged ischemic times (>8 hours)(PIT) compared with 14 with short ischemic times (< or =90 minutes)(SIT).

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Background And Objective: The physical mechanisms for laser-tattoo interactions and the tattoo particle breakup process are not well understood. This study investigates whether the mechanism of the breakup process can be identified via computer simulations and proposes a treatment strategy that can potentially minimize the collateral damage to the surrounding tissues. Note that the "removal" of tattoo particles is defined here as breakup of particles into smaller ones with sizes approaching or smaller than the visible wavelength of light so that they become less visible.

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Airway hyperresponsiveness, airway inflammation, and reversible airway obstruction are physiological hallmarks of asthma. These responses are increasingly being studied in murine models of antigen exposure and challenge, using whole body plethysmography to noninvasively assess airway hyperresponsiveness. This approach infrequently has been correlated with indexes of airway hyperresponsiveness measured by invasive means.

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