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Papers by Eric Yang
Journal of Chromatography B-analytical Technologies in The Biomedical and Life Sciences, 2004
In the present work, a high-throughput LC/MS/MS method using a Chromolith RP-18 ( mm) monolithic ... more In the present work, a high-throughput LC/MS/MS method using a Chromolith RP-18 ( mm) monolithic column was developed and partially validated for the determination of bupropion (BUP), an anti-depressant drug, and its metabolites, hydroxybupropion and threo-hydrobupropion (TB), in human, mouse, and rat plasma. A modern integrated liquid chromatograph and an LC/MS/MS system with a TurboIonSpray (TIS) interface were used for the positive electrospray selected reaction monitoring (SRM) LC/MS analyses. Spiked control plasma calibration standards and quality control (QC) samples were extracted by semi-automated 96-well liquid–liquid extraction (LLE) using ethyl acetate. A mobile phase consisting of 8 mM ammonium acetate-acetonitrile (55:45, v/v) delivered isocratically at 5 ml/min, and split post-column to 2 ml/min directed to the TIS, provided the optimum conditions for the chromatographic separation of bupropion and its metabolites within 23 s. The isotope-labeled D6-bupropion and D6-hydroxybupropion were used as internal standards. The method was linear over a concentration range of 0.25–200 ng/ml (bupropion and threo-hydrobupropion), and 1.25–1000 ng/ml (hydroxybupropion). The intra- and inter-day assay accuracy and precision were within 15% for all analytes in each of the biological matrices. The monolithic column performance as a function of column backpressure, peak asymmetry, and retention time reproducibility was adequately maintained over 864 extracted plasma injections.
Journal of Proteome Research, 2004
Endometrial carcinoma is a common malignancy in women, being exceeded in incidence only by that o... more Endometrial carcinoma is a common malignancy in women, being exceeded in incidence only by that of breast, lung, and colorectal cancers. At present, no serum tumor markers are available for the monitoring of endometrial carcinoma patients, and patients with recurrent disease are detected only following the development of symptoms or abnormalities in imaging assessments. Similarly, no screening tools are available for endometrial carcinoma. Protein profiling by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) has proven to be a sensitive and fast method of analysis for small proteins or peptides to yield specific biomarkers. In this study, a variety of normal and malignant endometrial tissue samples were fractionated and analyzed by SELDI-TOF MS (SELDI is a version of MALDI utilizing protein "chips"). A number of proteins displayed differential expression in malignant endometrial tissues. One of the prominent proteins fractionated by weak cation exchange chromatography and displaying enhanced expression in these malignant tissues was identified as chaperonin 10. The increased expression of chaperonin 10 in malignant endometrial tissues was further confirmed by parallel Western blot and immunohistochemistry analyses.
Proteomics, 2005
Surface-enhanced laser desorption/ionization-mass spectrometry (SELDI-MS) has conventionally been... more Surface-enhanced laser desorption/ionization-mass spectrometry (SELDI-MS) has conventionally been practiced on linear time of flight (TOF) which has low mass accuracy and resolution. Here we demonstrate in an examination of both malignant and nonmalignant endometrial tissue homogenates that high mass accuracy and resolution in the MS stage are crucial. Using a commercially available quadrupole/TOF (QqTOF), we were able to resolve two potential cancer markers, subsequently identified off-line as chaperonin 10 and calgranulin A, that differ by 8 Da in mass. Two off-line protein identification protocols were developed: the first was based on size-exclusion chromatography (SEC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), protein extraction, trypsin digestion, and matrix-assisted laser desorption/ionization-tandem MS (MALDI-MS/MS); the second on SEC and shotgun nano-liquid chromatography (nanoLC)-MS/MS. Analyses on a cohort of 44 endometrial homogenates showed 22 out of 23 nonmalignant samples had nondetectable to very low abundance of chaperonin 10 and calgranulin A; 17 of the 21 malignant samples had detectable to abundant levels of both proteins. Immunohistochemical staining of a tissue microarray of 32 samples showed that approximately half of malignant endometrial tissues exhibited positive staining for calgranulin A in the malignant epithelium, while 9 out of 10 benign tissues exhibited negative epithelial staining. In addition, macrophages/granulocytes in malignant as well as nonmalignant tissues showed positive staining. No immunostaining occurred in stroma or myometrium. Calgranulin A, in combination with chaperonin 10 and other proteins, may eventually constitute a panel of markers to permit diagnosis and screening of endometrial cancer.
American Journal of Cardiology, 2006
We sought to determine whether the echocardiographic Doppler parameters of left ventricular diast... more We sought to determine whether the echocardiographic Doppler parameters of left ventricular diastolic dysfunction predict future heart failure (HF) events and, if so, which parameters best predict HF. We also examined whether the predictive ability of echocardiographic Doppler parameters was related to their prediction of left ventricular end-diastolic pressure (LVEDP). We studied patients who underwent cardiac catheterization and echocardiography performed within a 30-day period. The end point was HF, defined as new-onset or recurrent HF diagnosed by a physician and requiring the initiation or modification of treatment of HF. We identified 289 patients (mean age 63.5 ± 12.6 years) with a mean follow-up of 10.9 ± 10.2 months. A total of 24 HF events occurred. LVEDP was a significant predictor of HF univariately and independently in multiple regression models after adjustment for ejection fraction. In Cox models adjusted for age, gender, LVEDP, and ejection fraction, only the left atrial volume index and early mitral inflow to early diastolic tissue velocity (E/e′) ratio remained predictive of HF. A multiple regression model, including all echocardiographic variables, showed a persistent, although attenuated, relation of early to late mitral inflow velocity (E/A) ratio and E/e′ with LVEDP (p = 0.06 and p = 0.002, respectively). The addition of E/e′ or the left atrial volume indexed to body surface area, but not E/A, to the clinical history and left ventricular ejection fraction provided incremental prognostic information. A LVEDP of ≥20 mm Hg, E/e′ ratio of ≥15, and left atrial volume index of ≥23 ml/m2 identified those with a higher risk of HF. In conclusion, invasively determined LVEDP is an independent predictor of future HF events. E/e′ and the left atrial volume indexed to body surface area are the best independent predictors of future HF and provide prognostic information incremental to the clinical history and left ventricular ejection fraction.
American Journal of Cardiology, 2006
We investigated the influence of ≥70% luminal coronary artery stenosis on regional diastolic defo... more We investigated the influence of ≥70% luminal coronary artery stenosis on regional diastolic deformation at rest using 2-dimensional strain echocardiography. We prospectively imaged patients during/within 24 hours of coronary angiography. Longitudinal systolic (SRs), early (SRe), and late diastolic strain rates, systolic, early, and late diastolic strain and times to isovolumic relaxation and peak SRe were measured in the 3 major vascular territories. Regions subtended by ≥70% coronary stenosis were labeled ischemic. Ischemic regions were compared with the same region in patients without significant coronary stenosis. Of 61 enrolled patients (38 men), 39 had ≥70% coronary stenosis (1 vessel in 14, 2 vessels in 15, 3 vessels in 10), and 15 had normal coronary arteries. There were no significant differences between the normal and ischemic groups with regard to age (59 ± 13 vs 64 ± 10 years, p = 0.20), clinical variables (dyslipidemia, smoking, diabetes), systolic (130 ± 26 vs 139 ± 31 mm Hg, p = 0.38) or diastolic (72 ± 13 vs 72 ± 11 mm Hg, p = 0.81) blood pressure and ejection fraction (58 ± 12% vs 56 ± 11%, p = 0.66). SRs and SRe were significantly decreased in ischemic compared with normal regions in all vascular distributions. SRs and SRe together (values below cutoff) or SRe alone were the most specific (93%) and SRe or SRs below cutoff the most sensitive (93%) parameters for detecting ischemic regions. In conclusion, analysis of regional deformation by 2-dimensional strain echocardiography enables detection of significantly diseased coronary arteries at rest. Altered diastolic deformation at rest identifies regions subtended by ≥70% coronary stenosis with high specificity.
Objective-The purpose of the current study was to determine whether lipoprotein-associated phosph... more Objective-The purpose of the current study was to determine whether lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is associated with coronary endothelial dysfunction and is a predictor of endothelial dysfunction in humans. (172) with no significant coronary artery disease (Ͻ30% stenosis) undergoing assessment of coronary endothelial function were studied. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Plasma concentrations of Lp-PLA 2 were measured, and patients were divided into tertiles. Patients in tertiles 2 and 3 had a significantly lower change in coronary blood flow 63.8Ϯ73.2 and 32.0Ϯ71.7 versus 78.4Ϯ73.2%; PϽ0.001) and greater epicardial coronary artery vasoconstriction (Ϫ14.1Ϯ14.7 and Ϫ23.3Ϯ25.1 versus Ϫ9.5Ϯ15.2% mean diameter change; PϽ0.001) in response to acetylcholine. Patients with coronary endothelial dysfunction had significantly higher serum concentrations of Lp-PLA 2 than those with normal endothelial function (246.2Ϯ71.6 versus 209Ϯ56.7 ng/mL; Pϭ0.001). The odds ratio for coronary endothelial dysfunction in patients with Lp-PLA 2 in the highest tertile was 3.3 (95% CI, 1.6 to 6.6). Conclusions-Lp-PLA 2 is independently associated with coronary artery endothelial dysfunction and is a strong predictor of endothelial dysfunction in humans. (Arterioscler Thromb Vasc Biol. 2006;26:0-0.)
International Immunopharmacology, 2002
There are complex bi-directional interactions among the central nervous system (CNS), the endocri... more There are complex bi-directional interactions among the central nervous system (CNS), the endocrine system, and the immune system. Although the mechanisms of this bi-directional communication is not yet fully understood, studies in the field of psychoneuroimmunology (PNI) have shown that stress, through the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal medullary (SAM) axes, can result in the dysregulation of the immune system. In this review, we discuss human studies and animal models, which focuses on psychological stress emphasizing the implications of these effects on wound healing and infectious diseases.
Journal of Neuroimmunology, 2002
Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs), whose e... more Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs), whose expression can be controlled by cytokines, play a role in extracellular matrix remodeling in physiological and pathological processes. Using a blister chamber wound model on UV-B-exposed human forearm skin, we examined whether stress or mood-associated neuroendocrine alteration is sufficient to modulate MMP and TIMP expression. We did not find evidence that depressive symptoms were reliably associated with modulation of either MMP or TIMP expression. However, we did find that activation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary (SAM) axes can modulate levels of MMPs. A positive association between plasma norepinephrine levels and MMP-2 protein levels, and a negative correlation between plasma cortisol levels and MMP-2 levels were found. The data suggest that activation of the HPA and SAM axes, even in individuals within the normal range of depressive symptoms, could mediate MMP levels and wound healing in blister wounds.
Brain Behavior and Immunity, 2005
Antibodies to several Epstein–Barr virus (EBV)-encoded enzymes are observed in patients with diff... more Antibodies to several Epstein–Barr virus (EBV)-encoded enzymes are observed in patients with different EBV-associated diseases. The reason for these antibody patterns and the role these proteins might play in the pathophysiology of disease, separate from their role in virus replication, is unknown. In this series of studies, we found that purified EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase) can inhibit the replication of human peripheral blood mononuclear cells in vitro and upregulate the production of TNF-α, IL-1β, IL-6, IL-8, and IL-10. It also enhanced the ability of natural killer cells to lyse target cells. The EBV dUTPase also significantly inhibited the replication of mitogen-stimulated lymphocytes and the synthesis of IFN-γ by cells isolated from lymph nodes and spleens obtained from mice inoculated with the protein. It also produced sickness behaviors known to be induced by some of the cytokines that were studied in the in vitro experiments. These symptoms include an increase in body temperature, a decrease in body mass and in physical activity. The data provide a new perspective on how an early nonstructural EBV-encoded protein can cause immune dysregulation and produce clinical symptoms observed in patients with chronic fatigue syndrome (CFS) separate from its role in virus replication and may serve as a new approach to help identify one of the etiological agents for CFS. The data also provide additional insight into the pathophysiology of EBV infection, inflammation, and cancer.
Brain Behavior and Immunity, 2003
Journal of Chromatography B-analytical Technologies in The Biomedical and Life Sciences, 2004
In the present work, a high-throughput LC/MS/MS method using a Chromolith RP-18 ( mm) monolithic ... more In the present work, a high-throughput LC/MS/MS method using a Chromolith RP-18 ( mm) monolithic column was developed and partially validated for the determination of bupropion (BUP), an anti-depressant drug, and its metabolites, hydroxybupropion and threo-hydrobupropion (TB), in human, mouse, and rat plasma. A modern integrated liquid chromatograph and an LC/MS/MS system with a TurboIonSpray (TIS) interface were used for the positive electrospray selected reaction monitoring (SRM) LC/MS analyses. Spiked control plasma calibration standards and quality control (QC) samples were extracted by semi-automated 96-well liquid–liquid extraction (LLE) using ethyl acetate. A mobile phase consisting of 8 mM ammonium acetate-acetonitrile (55:45, v/v) delivered isocratically at 5 ml/min, and split post-column to 2 ml/min directed to the TIS, provided the optimum conditions for the chromatographic separation of bupropion and its metabolites within 23 s. The isotope-labeled D6-bupropion and D6-hydroxybupropion were used as internal standards. The method was linear over a concentration range of 0.25–200 ng/ml (bupropion and threo-hydrobupropion), and 1.25–1000 ng/ml (hydroxybupropion). The intra- and inter-day assay accuracy and precision were within 15% for all analytes in each of the biological matrices. The monolithic column performance as a function of column backpressure, peak asymmetry, and retention time reproducibility was adequately maintained over 864 extracted plasma injections.
Journal of Proteome Research, 2004
Endometrial carcinoma is a common malignancy in women, being exceeded in incidence only by that o... more Endometrial carcinoma is a common malignancy in women, being exceeded in incidence only by that of breast, lung, and colorectal cancers. At present, no serum tumor markers are available for the monitoring of endometrial carcinoma patients, and patients with recurrent disease are detected only following the development of symptoms or abnormalities in imaging assessments. Similarly, no screening tools are available for endometrial carcinoma. Protein profiling by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) has proven to be a sensitive and fast method of analysis for small proteins or peptides to yield specific biomarkers. In this study, a variety of normal and malignant endometrial tissue samples were fractionated and analyzed by SELDI-TOF MS (SELDI is a version of MALDI utilizing protein "chips"). A number of proteins displayed differential expression in malignant endometrial tissues. One of the prominent proteins fractionated by weak cation exchange chromatography and displaying enhanced expression in these malignant tissues was identified as chaperonin 10. The increased expression of chaperonin 10 in malignant endometrial tissues was further confirmed by parallel Western blot and immunohistochemistry analyses.
Proteomics, 2005
Surface-enhanced laser desorption/ionization-mass spectrometry (SELDI-MS) has conventionally been... more Surface-enhanced laser desorption/ionization-mass spectrometry (SELDI-MS) has conventionally been practiced on linear time of flight (TOF) which has low mass accuracy and resolution. Here we demonstrate in an examination of both malignant and nonmalignant endometrial tissue homogenates that high mass accuracy and resolution in the MS stage are crucial. Using a commercially available quadrupole/TOF (QqTOF), we were able to resolve two potential cancer markers, subsequently identified off-line as chaperonin 10 and calgranulin A, that differ by 8 Da in mass. Two off-line protein identification protocols were developed: the first was based on size-exclusion chromatography (SEC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), protein extraction, trypsin digestion, and matrix-assisted laser desorption/ionization-tandem MS (MALDI-MS/MS); the second on SEC and shotgun nano-liquid chromatography (nanoLC)-MS/MS. Analyses on a cohort of 44 endometrial homogenates showed 22 out of 23 nonmalignant samples had nondetectable to very low abundance of chaperonin 10 and calgranulin A; 17 of the 21 malignant samples had detectable to abundant levels of both proteins. Immunohistochemical staining of a tissue microarray of 32 samples showed that approximately half of malignant endometrial tissues exhibited positive staining for calgranulin A in the malignant epithelium, while 9 out of 10 benign tissues exhibited negative epithelial staining. In addition, macrophages/granulocytes in malignant as well as nonmalignant tissues showed positive staining. No immunostaining occurred in stroma or myometrium. Calgranulin A, in combination with chaperonin 10 and other proteins, may eventually constitute a panel of markers to permit diagnosis and screening of endometrial cancer.
American Journal of Cardiology, 2006
We sought to determine whether the echocardiographic Doppler parameters of left ventricular diast... more We sought to determine whether the echocardiographic Doppler parameters of left ventricular diastolic dysfunction predict future heart failure (HF) events and, if so, which parameters best predict HF. We also examined whether the predictive ability of echocardiographic Doppler parameters was related to their prediction of left ventricular end-diastolic pressure (LVEDP). We studied patients who underwent cardiac catheterization and echocardiography performed within a 30-day period. The end point was HF, defined as new-onset or recurrent HF diagnosed by a physician and requiring the initiation or modification of treatment of HF. We identified 289 patients (mean age 63.5 ± 12.6 years) with a mean follow-up of 10.9 ± 10.2 months. A total of 24 HF events occurred. LVEDP was a significant predictor of HF univariately and independently in multiple regression models after adjustment for ejection fraction. In Cox models adjusted for age, gender, LVEDP, and ejection fraction, only the left atrial volume index and early mitral inflow to early diastolic tissue velocity (E/e′) ratio remained predictive of HF. A multiple regression model, including all echocardiographic variables, showed a persistent, although attenuated, relation of early to late mitral inflow velocity (E/A) ratio and E/e′ with LVEDP (p = 0.06 and p = 0.002, respectively). The addition of E/e′ or the left atrial volume indexed to body surface area, but not E/A, to the clinical history and left ventricular ejection fraction provided incremental prognostic information. A LVEDP of ≥20 mm Hg, E/e′ ratio of ≥15, and left atrial volume index of ≥23 ml/m2 identified those with a higher risk of HF. In conclusion, invasively determined LVEDP is an independent predictor of future HF events. E/e′ and the left atrial volume indexed to body surface area are the best independent predictors of future HF and provide prognostic information incremental to the clinical history and left ventricular ejection fraction.
American Journal of Cardiology, 2006
We investigated the influence of ≥70% luminal coronary artery stenosis on regional diastolic defo... more We investigated the influence of ≥70% luminal coronary artery stenosis on regional diastolic deformation at rest using 2-dimensional strain echocardiography. We prospectively imaged patients during/within 24 hours of coronary angiography. Longitudinal systolic (SRs), early (SRe), and late diastolic strain rates, systolic, early, and late diastolic strain and times to isovolumic relaxation and peak SRe were measured in the 3 major vascular territories. Regions subtended by ≥70% coronary stenosis were labeled ischemic. Ischemic regions were compared with the same region in patients without significant coronary stenosis. Of 61 enrolled patients (38 men), 39 had ≥70% coronary stenosis (1 vessel in 14, 2 vessels in 15, 3 vessels in 10), and 15 had normal coronary arteries. There were no significant differences between the normal and ischemic groups with regard to age (59 ± 13 vs 64 ± 10 years, p = 0.20), clinical variables (dyslipidemia, smoking, diabetes), systolic (130 ± 26 vs 139 ± 31 mm Hg, p = 0.38) or diastolic (72 ± 13 vs 72 ± 11 mm Hg, p = 0.81) blood pressure and ejection fraction (58 ± 12% vs 56 ± 11%, p = 0.66). SRs and SRe were significantly decreased in ischemic compared with normal regions in all vascular distributions. SRs and SRe together (values below cutoff) or SRe alone were the most specific (93%) and SRe or SRs below cutoff the most sensitive (93%) parameters for detecting ischemic regions. In conclusion, analysis of regional deformation by 2-dimensional strain echocardiography enables detection of significantly diseased coronary arteries at rest. Altered diastolic deformation at rest identifies regions subtended by ≥70% coronary stenosis with high specificity.
Objective-The purpose of the current study was to determine whether lipoprotein-associated phosph... more Objective-The purpose of the current study was to determine whether lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is associated with coronary endothelial dysfunction and is a predictor of endothelial dysfunction in humans. (172) with no significant coronary artery disease (Ͻ30% stenosis) undergoing assessment of coronary endothelial function were studied. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Plasma concentrations of Lp-PLA 2 were measured, and patients were divided into tertiles. Patients in tertiles 2 and 3 had a significantly lower change in coronary blood flow 63.8Ϯ73.2 and 32.0Ϯ71.7 versus 78.4Ϯ73.2%; PϽ0.001) and greater epicardial coronary artery vasoconstriction (Ϫ14.1Ϯ14.7 and Ϫ23.3Ϯ25.1 versus Ϫ9.5Ϯ15.2% mean diameter change; PϽ0.001) in response to acetylcholine. Patients with coronary endothelial dysfunction had significantly higher serum concentrations of Lp-PLA 2 than those with normal endothelial function (246.2Ϯ71.6 versus 209Ϯ56.7 ng/mL; Pϭ0.001). The odds ratio for coronary endothelial dysfunction in patients with Lp-PLA 2 in the highest tertile was 3.3 (95% CI, 1.6 to 6.6). Conclusions-Lp-PLA 2 is independently associated with coronary artery endothelial dysfunction and is a strong predictor of endothelial dysfunction in humans. (Arterioscler Thromb Vasc Biol. 2006;26:0-0.)
International Immunopharmacology, 2002
There are complex bi-directional interactions among the central nervous system (CNS), the endocri... more There are complex bi-directional interactions among the central nervous system (CNS), the endocrine system, and the immune system. Although the mechanisms of this bi-directional communication is not yet fully understood, studies in the field of psychoneuroimmunology (PNI) have shown that stress, through the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal medullary (SAM) axes, can result in the dysregulation of the immune system. In this review, we discuss human studies and animal models, which focuses on psychological stress emphasizing the implications of these effects on wound healing and infectious diseases.
Journal of Neuroimmunology, 2002
Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs), whose e... more Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs), whose expression can be controlled by cytokines, play a role in extracellular matrix remodeling in physiological and pathological processes. Using a blister chamber wound model on UV-B-exposed human forearm skin, we examined whether stress or mood-associated neuroendocrine alteration is sufficient to modulate MMP and TIMP expression. We did not find evidence that depressive symptoms were reliably associated with modulation of either MMP or TIMP expression. However, we did find that activation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary (SAM) axes can modulate levels of MMPs. A positive association between plasma norepinephrine levels and MMP-2 protein levels, and a negative correlation between plasma cortisol levels and MMP-2 levels were found. The data suggest that activation of the HPA and SAM axes, even in individuals within the normal range of depressive symptoms, could mediate MMP levels and wound healing in blister wounds.
Brain Behavior and Immunity, 2005
Antibodies to several Epstein–Barr virus (EBV)-encoded enzymes are observed in patients with diff... more Antibodies to several Epstein–Barr virus (EBV)-encoded enzymes are observed in patients with different EBV-associated diseases. The reason for these antibody patterns and the role these proteins might play in the pathophysiology of disease, separate from their role in virus replication, is unknown. In this series of studies, we found that purified EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase) can inhibit the replication of human peripheral blood mononuclear cells in vitro and upregulate the production of TNF-α, IL-1β, IL-6, IL-8, and IL-10. It also enhanced the ability of natural killer cells to lyse target cells. The EBV dUTPase also significantly inhibited the replication of mitogen-stimulated lymphocytes and the synthesis of IFN-γ by cells isolated from lymph nodes and spleens obtained from mice inoculated with the protein. It also produced sickness behaviors known to be induced by some of the cytokines that were studied in the in vitro experiments. These symptoms include an increase in body temperature, a decrease in body mass and in physical activity. The data provide a new perspective on how an early nonstructural EBV-encoded protein can cause immune dysregulation and produce clinical symptoms observed in patients with chronic fatigue syndrome (CFS) separate from its role in virus replication and may serve as a new approach to help identify one of the etiological agents for CFS. The data also provide additional insight into the pathophysiology of EBV infection, inflammation, and cancer.
Brain Behavior and Immunity, 2003