International Journal of Medical Sciences http://www.medsci.org International Journal of Medical Sciences RSS feed -- Volume 5 en-us Sat, 10 May 2008 04:00:00 GMT Sat, 10 May 2008 04:00:00 GMT http://www.medsci.org/v05p0100.htm MAINTENANCE HORMONAL TREATMENT IMPROVES PROGRESSION FREE SURVIVAL AFTER A FIRST LINE CHEMOTHERAPY IN PATIENTS WITH METASTATIC BREAST CANCER http://www.medsci.org/v05p0100.htm The present study was conducted in patients with metastatic breast cancer. Its aim was to identify the factors which influence progression -free survival (PFS) and overall survival (OS) after the first line of chemotherapy in patients with positive tumour hormone receptor status. The patients with early disease progression during first-line chemotherapy were not included. In total, 560 patients who achieved a stable disease or a response to first-line chemotherapy were studied. The factors identified to improve the duration of PFS or OS in multivariate analysis were: number of metastatic sites (p = .01; p = .01), metastatic sites (p = .02; p = .04), Disease free interval (p = .001; p < .0001), previous hormonal therapy (p = .03; p = ns), response to first line chemotherapy (p < .0001; p = 0.0001) and an administration of maintenance hormonal therapy (p < .0001; p = .001). The major impact obtained by maintenance hormonal treatment after first-line chemotherapy in this study seems to indicate that this strategy should be recommended in patients with an ER or PgR positive tumour.

]]> Armelle Dufresne, Xavier Pivot, Christophe Tournigand, Thomas Facchini, Thierry Alweeg, Loic Chaigneau, Aimery De Gramont Ivyspring International Publisher 5 2 100 105 2008-5-5 Research Paper http://www.medsci.org/v05p0092.htm Vgf is a novel biomarker associated with muscle weakness in amyotrophic lateral sclerosis (ALS), with a potential role in disease pathogenesis http://www.medsci.org/v05p0092.htm Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Previous proteomic evidence revealed that the content of certain peptide fragments including Vgf-derived peptide aa 398-411 (Vgf398-411) of the precursor Vgf protein in the cerebral spinal fluid (CSF) correctly identified patients with ALS from normal and disease controls. Using quantitative ELISA immunoassay we found that the CSF levels of Vgf decreases with muscle weakness in patients with ALS. In SOD1 G93A transgenic mice, loss of full-length Vgf content in CSF, serum and in SMI-32 immunopositive spinal cord motor neurons is noted in asymptomatic animals (approximately 75 days old) and continues to show a progressive decline as animals weaken. In vitro studies show that viral-mediated exogenous Vgf expression in primary mixed spinal cord neuron cultures attenuates excitotoxic injury. Thus, while Vgf may be a reliable biomarker of progression of muscle weakness in patients with ALS, restoration of Vgf expression in spinal cord motor neurons may therapeutically rescue spinal cord motorneurons against excitotoxic injury.

]]> Zhong Zhao, Dale J. Lange, Lap Ho, Sara Bonini, Belinda Shao, Stephen R. Salton, Sunil Thomas, Giulio Maria Pasinetti Ivyspring International Publisher 5 2 92 99 2008-4-15 Research Paper http://www.medsci.org/v05p0087.htm TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders http://www.medsci.org/v05p0087.htm Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x109/L. A reduction of platelets to <600 in asymptomatic or <400 x 109/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.

]]> Jan Palmblad, Magnus Björkholm, Jack Kutti, Gerd Lärfars, Eva Löfvenberg, Berit Markevärn, Mats Merup, Nils Mauritzson, Jan Westin, Jan Samuelsson, Gunnar Birgegård Ivyspring International Publisher 5 2 87 91 2008-4-13 Research Paper http://www.medsci.org/v05p0080.htm VEGF T-1498C polymorphism, a predictive marker of differentiation of colorectal adenocarcinomas in Japanese http://www.medsci.org/v05p0080.htm Background: Previously, MDR1 T-129C polymorphism, encoding multidrug resistant transporter MDR1/P-glycoprotein, was reported to be predictive of poorly-differentiated colorectal adenocarcinomas. Here, VEGF T-1498C, C-634G and C-7T polymorphisms, encoding vascular endothelial growth factor (VEGF), were investigated in terms of their association with differentiation grade.

Methods: VEGF genotypes were determined by TaqManR MGB probe based polymerase chain reaction and evaluated were confirmed by direct sequencing in 36 Japanese patients.

Results: VEGF T-1498C, but not C-634G or C-7T, was predictive of poorly-differentiated ones, and thereby a poor prognosis (p = 0.064 for genotype, p = 0.037 for allele), and this effect can be explained by that on VEGF expression. Treatment of a colorectal adenocarcinoma cell line, HCT-15, with sodium butyrate, a typical differentiating agent, resulted in an increase of alkaline phosphatase activity and MDR1 mRNA expression, but in a decrease of VEGF mRNA expression. The transfection of VEGF small interfering RNA (siRNA) induced the expression of MDR1 mRNA to 288-332% of the control level, whereas MDR1 siRNA had no effect on VEGF mRNA expression.

Conclusions: VEGF T-1498C polymorphism is also a candidate marker predictive of poorly-differentiated colorectal adenocarcinomas, but further investigations with a large number of patients should be addressed to draw a conclusion.

]]> Motohiro Yamamori, Mayuko Taniguchi, Shingo Maeda, Tsutomu Nakamura, Noboru Okamura, Akiko Kuwahara, Koichi Iwaki, Takao Tamura, Nobuo Aoyama, Svetlana Markova, Masato Kasuga, Katsuhiko Okumura, Toshiyuki Sakaeda Ivyspring International Publisher 5 2 80 86 2008-4-8 Research Paper http://www.medsci.org/v05p0073.htm Expression and function of micro RNAs in immune cells during normal or disease state http://www.medsci.org/v05p0073.htm Micro RNAs (miRNAs) are 19-24 nucleotide long non-coding RNAs that posttranscriptionally modulate gene expression. They are found in almost all species: viruses, plants, nematodes, fly, fish, mouse, human, and are implicated in a wide array of cellular and developmental processes. Microarray-based miRNA profiling brought to the discovery of miRNAs specific to different hematopoietic lineages. Furthermore, the functional assays performed in tissue cultures to discover miRNAs involved in immune responses in combination with the reports of miRNA-transgenic or miRNA-knockout mouse models has helped elucidating the miRNA roles in the development and function of immune system. Abnormal patterns of hematopoietic-specific miRNAs have been found in different types of cancer and miRNA based gene therapy is being considered as a potential technology of choice in immunological disorders and cancer. The purpose of this review is to discuss recent findings related with the expression and function of miRNAs in hematopoietic lineages.

]]> Esmerina Tili, Jean-Jacques Michaille, George Adrian Calin Ivyspring International Publisher 5 2 73 79 2008-4-3 Review http://www.medsci.org/v05p0068.htm Principal Investigator Views of the IRB System http://www.medsci.org/v05p0068.htm We undertook a qualitative e-mail survey of federally-funded principal investigators of their views of the US human subjects protection system, intended to identify the range of investigator attitudes. This was an exploratory study with a 14% response rate. Twenty-eight principal investigators responded; their comments were analyzed to show underlying themes, which are here presented along with supporting quotations.

There was consensus that it is important to protect human subjects from research abuse, but disagreement over how well the IRB system is functioning. Some researchers felt that the system is effective and serves its purpose well. Of those who support the system, some endorse its methods, purpose, and daily functioning, as they experience it, without reservation. Others, while expressing some frustration, feel that the purpose is important and their local IRB does its best to make a difficult system work well.

Those investigators who were more harshly critical commented on multiple flaws in the system, including (1) consent forms that are inappropriate and incomprehensible, (2) an emphasis on minutiae, and (3) concern with protecting the institution more than research subjects. Respondents told us that the IRB system is a particular burden for research in neurology, emergency medical conditions, repositories, and social sciences in general; a more comprehensive study might identify other problematic areas. Significant concern was expressed about the cost, inefficiency, and irrationality of IRB review. The IRB system works well for some researchers, but our results indicate that other investigators feel the costs outweigh the benefits.

]]> Simon N. Whitney, Kirsten Alcser, Carl E. Schneider, Laurence B. McCullough, Amy L. McGuire, Robert J. Volk Ivyspring International Publisher 5 2 68 72 2008-4-2 Short Research Communication http://www.medsci.org/v05p0062.htm A 12 Week, Open Label, Phase I/IIa Study Using Apatone® for the Treatment of Prostate Cancer Patients Who Have Failed Standard Therapy http://www.medsci.org/v05p0062.htm Purpose: To evaluate the safety and efficacy of oral Apatone® (Vitamin C and Vitamin K3) administration in the treatment of prostate cancer in patients who failed standard therapy.

Materials and Methods: Seventeen patients with 2 successive rises in PSA after failure of standard local therapy were treated with (5,000 mg of VC and 50 mg of VK3 each day) for a period of 12 weeks. Prostate Specific Antigen (PSA) levels, PSA velocity (PSAV) and PSA doubling times (PSADT) were calculated before and during treatment at 6 week intervals. Following the initial 12 week trial, 15 of 17 patients opted to continue treatment for an additional period ranging from 6 to 24 months. PSA values were followed for these patients.

Results: At the conclusion of the 12 week treatment period, PSAV decreased and PSADT increased in 13 of 17 patients (p ≤ 0.05). There were no dose-limiting adverse effects. Of the 15 patients who continued on Apatone after 12 weeks, only 1 death occurred after 14 months of treatment.

Conclusion: Apatone showed promise in delaying biochemical progression in this group of end stage prostate cancer patients.

]]> Basir Tareen, Jack L. Summers, James M. Jamison, Deborah R. Neal, Karen McGuire, Lowell Gerson, Ananias Diokno Ivyspring International Publisher 5 2 62 67 2008-3-24 Research Paper http://www.medsci.org/v05p0050.htm Computerized two-lead resting ECG analysis for the detection of coronary artery stenosis after coronary revascularization http://www.medsci.org/v05p0050.htm Background: Resting electrocardiogram (ECG) shows limited sensitivity and specificity for the detection of coronary artery disease (CAD), where patients with a history of coronary revascularization may pose special challenges. Several methods exist to enhance sensitivity and specificity of resting ECG for diagnosis of CAD, but such methods are not better than a specialist's judgement. We compared a new computer-enhanced, resting ECG analysis device, 3DMP, to coronary angiography to evaluate the device's accuracy in detecting hemodynamically relevant CAD.

Methods: A convenience sample of 172 patients with a history of coronary revascularization scheduled for coronary angiography was evaluated with 3DMP before coronary angiography. 3DMP's sensitivity and specificity in detecting hemodynamically relevant coronary stenosis as diagnosed with coronary angiography were calculated as well as odds ratios for the 3DMP severity score and coronary artery disease risk factors.

Results: The 3DMP system accurately identified 50 of 55 patients as having hemodynamically relevant stenosis (sensitivity 90.9%, specificity 88.0%). Positive and negative predictive values for the identification of coronary stenosis as diagnosed in coronary angiograms were 62.7% and 97.8% respectively. Risk and demographic factors in a logistic regression model had a markedly lower predictive power for the presence of coronary stenosis in these patients than did 3DMP severity score (odds ratio 2.04 [0.74-5.62] vs. 73.57 [25.10-215.68]). A logistic regression combining severity score with risk and demographic factors did not add significantly to the prediction quality (odds ratio 80.00 [27.03-236.79]).

Conclusions: 3DMP's computer-based, mathematically derived analysis of resting two-lead ECG data provides detection of hemodynamically relevant CAD in patients with a history of coronary revascularization with high sensitivity and specificity that appears to be at least as good as those reported for other resting and/or stress ECG methods currently used in clinical practice.

]]> Eberhard Grube, Andreas Bootsveld, Lutz Buellesfeld, Seyrani Yuecel, Joseph T Shen, Michael Imhoff Ivyspring International Publisher 5 2 50 61 2008-3-2 Research Paper http://www.medsci.org/v05p0041.htm Qualitative Dosimetric and Radiobiological Evaluation of High – Dose – Rate Interstitial brachytherapy Implants http://www.medsci.org/v05p0041.htm Radiation quality indices (QI), tumor control probability (TCP), and normal tissue complication probability(NTCP) were evaluated for ideal single and double plane HDR interstitial implants. In the analysis, geometrically–optimized at volume (GOV) treatment plans were generated for different values of inter–source–spacing (ISS) within the catheter, inter–catheter–spacing (ICS), and inter–plane–spacing (IPS) for single - and double - plane implants. The dose volume histograms (DVH) were generated for each plan, and the coverage volumes of 100%, 150%, and 200% were obtained to calculate QIs, TCP, and NTCP. Formulae for biologically effective equivalent uniform dose (BEEUD), for tumor and normal tissues, were derived to calculate TCP and NTCP. Optimal values of QIs, except external volume index (EI), and TCP were obtained at ISS = 1.0 cm, and ICS = 1.0 cm, for single–plane implants, and ISS = 1.0 cm, ICS = 1.0 cm, and IPS = 0.75 to 1.25 cm, for double – plane implants. From this study, it is assessed that ISS = 1.0 cm, ICS = 1.0 cm, for single - plane implant and IPS between 0.75 cm to 1.25 cm provide better dose conformity and uniformity.

]]> Than S. Kehwar, Syed F. Akber, Kamlesh Passi Ivyspring International Publisher 5 1 41 49 2008-2-19 Research Paper http://www.medsci.org/v05p0036.htm Correlation of the Radiographic and Morphological Features of the Dental Follicle of Third Molars with Incomplete Root Formation http://www.medsci.org/v05p0036.htm The objective of this study was to determine the correlation of the radiographic and morphological features of the dental follicle of unerupted third molars with incomplete root formation. A cross-sectional study was carried out with 56 patients (105 teeth) aged 13 to 24 years. Panoramic radiography was used to determine the stage of root formation to locate and measure pericoronal radiolucency. The width of the dental follicle ranged from 0.0 to 4.0 mm, the distal face being the one most frequently involved, and stage 7 of root formation showing the highest incidence. An inactive enamel reduced epithelium and inactive epithelium remnant also showed a high incidence. Dense connective tissue showed a high incidence, chronic inflammation was infrequent and calcification was a common finding. There was a significant association between the progression of the rhizogenesis and the transformation of the enamel reduced epithelium into a stratified squamous epithelium. No significant association was found between rhizogenesis and the other morphological findings or between the latter and the width of the pericoronal space. It was concluded that there was no clinically significant correlation between the radiographic and morphological features. Every asymptomatic unerupted third molar should be followed up and the follicular tissue analyzed.

]]> David Moraes de OLIVEIRA, Emanuel Sávio de Souza ANDRADE, Márcia Maria Fonseca da SILVEIRA, Igor Batista CAMARGO Ivyspring International Publisher 5 1 36 40 2008-2-8 Research Paper http://www.medsci.org/v05p0029.htm Association Study of Aromatase Gene (CYP19A1) in Essential Hypertension http://www.medsci.org/v05p0029.htm Background: As aromatase-deficient mice, which are deficient in estrogens, reportedly have reduced blood pressure, the aromatase gene (CYP19A1) is thought to be a susceptibility gene for essential hypertension (EH). The aim of the present study was to investigate the relationship between CYP19A1 and EH by examining single nucleotide polymorphisms (SNPs).

Methods: Five SNPs in the human CYP19A1 gene (rs1870049, rs936306, rs700518, rs10046 and rs4646) were selected, and an association study was performed in 218 Japanese EH patients and 225 age-matched normotensive (NT) individuals.

Results: There were significant differences between these groups in the distribution of genotypes rs700518 and rs10046 in male subjects, and genotypes rs700518, rs10046 and rs4646 in female subjects. On multiple logistic regression analysis, a significant association between rs700518 (p=0.023) and rs10046 (p=0.036) in male subjects and rs700518 in female subjects (p=0.018) was noted. Interestingly, the risk genotypes of rs700518 and rs10046 showed a sex-dependent inverse relationship. Both SBP and DBP levels were higher in total (cases and controls) male subjects with the G/G genotype with rs700518 or the T/T genotype with rs10046 than in male subjects without the G/G genotype or T/T genotype. SBP levels were lower in female subjects with the G/G genotype with rs700518 than in female subjects without G/G. The A-T haplotype constructed with rs1870049 and rs10046 was a susceptibility marker for EH.

Conclusions: We confirmed that rs700518 and rs10046, as well as a haplotype constructed with rs1870049 and rs10046, in the human CYP19A1 gene can be used as genetic markers for gender-specific EH.

]]> Masanori Shimodaira, Tomohiro Nakayama, Naoyuki Sato, Kosuke Saito, Akihiko Morita, Ichiro Sato, Teruyuki Takahashi, Masayoshi Soma, Yoichi Izumi Ivyspring International Publisher 5 1 29 35 2008-2-7 Research Paper http://www.medsci.org/v05p0024.htm Physical Exercise and Quality of Life in Breast Cancer Survivors http://www.medsci.org/v05p0024.htm An important goal for cancer patients is to improve the quality of life (QOL) by maximising functions affected by the disease and its therapy. Preliminary research suggests that exercise may be an effective intervention for enhancing QOL in cancer survivors. Research has provided preliminary evidence for the safety, feasibility, and efficacy of exercise training in breast cancer survivors. The aim of this study was to assess the association between physical exercise and quality of life in a population of female breast cancer survivors, followed up from diagnosis to the off-treatment time period, and investigated about their exercise habits in pre-diagnosis.

A total of 212 female breast cancer survivors consecutively registered from January 2002 to December 2006 at a Supportive Care Unit in an Italian Oncology Department were enrolled. Exercise behaviour was assessed by the Leisure Score Index (LSI) of the Godin Leisure-Time Exercise Questionnaire. Patients were asked to report their average weekly exercise for three cancer-related time periods, i.e. pre-diagnosis, during active treatment and off-treatment. Quality of life was assessed by the Italian version of the WHOQOL-BREF standardised instrument.

Statistical analysis indicated significant differences across the cancer-relevant time-periods for all exercise behaviour outcomes: the exercise behaviour was significantly lower during both on- and off- treatment than during prediagnosis; exercise during active treatment was significantly lower than during off-treatment. QOL strongly decreases during active treatment. Significant correlations were found between total exercise on- and off-treatment and all QOL indicators. Strenuous exercise is strongly correlated with QOL. Absent/mild exercise seems to be inversely correlated with a positive perception of disease severity and with quality of life on all axes.

Need clearly results for inclusion of physical activity programs in comprehensive, complementary treatment regimes for breast cancer patients in Italian oncology departments.

]]> Marco VALENTI, Giampiero PORZIO, Federica AIELLI, Lucilla VERNA, Katia CANNITA, Renato MANNO, Francesco MASEDU, Paolo MARCHETTI, Corrado FICORELLA Ivyspring International Publisher 5 1 24 28 2008-1-15 Research Paper http://www.medsci.org/v05p0018.htm Plasmatic B-Type Natriuretic Peptide and C-Reactive Protein in Hyperacute Stroke as Markers of Ct-Evidence of Brain Edema http://www.medsci.org/v05p0018.htm OBJECTIVE. Plasmatic B-type-natriuretic peptide (NT-PBNP) and C-reactive protein (CRP) have been reportedly elevated in stroke patients; however their clinical significance remains uncertain. The purpose of this work is to investigate whether elevation of these proteins at baseline predicts CT-evidence of brain edema.

METHODS. We recruited 41 consecutive patients with stroke and determined NT-PBNP and CRP at baseline (within 5 hours after onset), after 48-72 hours, and at discharge. Stroke severity was measured by means of the NIHS scale at baseline and at discharge. We also carried out brain CT at admittance and after 48 hours.

RESULTS. There were 29 ischemic strokes and 12 hemorrhagic strokes. Evidence of brain edema on delayed scan was seen in 14 patients. Baseline levels of NT-PBNP did not predict CT-evidence of edema but CRP levels did so significantly (0.7 mg/dl in patients without edema versus 4.7 mg in patients with edema; p=0.001). Both NT-PBNP and PC levels correlated poorly to NIHSS score and increased markedly from baseline to the second determination in patients with edema. For these patients the NT-PBNP increase was 133.6 pmol/l in comparison to 1.58 pmol/l in patients without edema (p=0.002). Neither CRP nor NT-PBNP baseline levels were predictive of dependency or death.

CONCLUSIONS. We conclude that CRP at baseline but not NT-PBNP predicts CT evidence of brain edema in stroke patients. We hypothesize that NT-PBNP levels elevated in response to edema after 48 hours of admission.

]]> Pedro J Modrego, Beatriz Boned, Juan J Berlanga, Mercedes Serrano Ivyspring International Publisher 5 1 18 23 2008-1-13 Research Paper http://www.medsci.org/v05p0009.htm Does eGFR improve the diagnostic capability of S-Creatinine concentration results? A retrospective population based study http://www.medsci.org/v05p0009.htm The use of MDRD-eGFR to diagnose Chronic Kidney Disease (CKD) is based on the assumption that the algorithm will minimize the influence of age, gender and ethnicity that is observed in S-Creatinine concentration and thus allow a single cut-off at which further diagnostic and therapeutic actions should be considered. This hypothesis is tested in a retrospective analysis of outpatients (N=93,404) and hospitalised (N=35,572) patients in UK and Sweden, respectively. An algorithm based on the same model as the MDRD-eGFR algorithm was derived from simultaneously measured S-Creatinine concentrations and Iohexol GFR in a subset of 565 patients. The combined uncertainty of using this algorithm was estimated to about 15 % which is about three times that of the S-Creatinine concentration results. The diagnostic performance of S-Creatinine concentration was evaluated using the Iohexol clearance as the reference procedure. It was shown that the diagnostic capacity of MDRD-eGFR, as it stands, has no added value compared to S-Creatinine. The gender and age differences of the S-Creatinine concentrations in the dataset persist after applying the MDRD-eGFR algorithm. Thus, a general use of the MDRD-eGFR does not seem justified. Furthermore the claim that the eGFR is adjusted for body area is misleading; the algorithm does not include any body size marker. It is thus a dangerous marker for guiding drug administration.

]]> Anders Kallner, Peter A Ayling, Zahra Khatami Ivyspring International Publisher 5 1 9 17 2008-1-5 Research Paper http://www.medsci.org/v05p0001.htm Differential Constitutive and Cytokine-Modulated Expression of Human Toll-like Receptors in Primary Neutrophils, Monocytes, and Macrophages http://www.medsci.org/v05p0001.htm Human Toll-like receptors (TLRs) comprise a family of proteins that recognizes pathogen-associated molecular patterns (PAMPs) and initiates host innate immune responses. Neutrophils, monocytes, and macrophages are critical cellular components of the human innate immune system. Proinflammatory cytokines, such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interferon-γ (IFN-γ), have been shown to up-regulate microbicidal activity in these effector cells of innate immunity. Currently, the cellular and molecular mechanisms responsible for these effects are not completely understood. We hypothesized that these cytokines may up-regulate TLR expression as a mechanism to facilitate microbial recognition and augment the innate immune response. Using quantitative realtime rt-PCR technology, we examined constitutive expression of TLR2, TLR4, TLR5, and TLR9 mRNA and the effects of G-CSF, GM-CSF, M-CSF, and IFN-γ on TLR mRNA expression in purified populations of normal human neutrophils, monocytes, and monocyte-derived macrophages. Relative constitutive expression of TLR2, TLR4, and TLR9 was similar in neutrophils and monocytes. Constitutive expression of TLR5 was less in neutrophils compared to monocytes. Constitutive expression of TLR4 was greater and that of TLR9 lower in monocyte-derived macrophages compared to monocytes. Of the cytokines examined, IFN-γ and GM-CSF caused the greatest effects on TLR expression. IFN- γ up-regulated TLR2 and TLR4 in neutrophils and monocytes. GM-CSF up-regulated expression of TLR2 and TLR4 in neutrophils and TLR2 in monocytes. TLR5 was down-regulated by inflammatory cytokines in monocytes. These results suggest a potential role for IFN- γ and/or GM-CSF as therapeutic immunomodulators of the host defense to infection.

]]> D. Shane O'Mahony, Uyenvy Pham, Ramesh Iyer, Thomas R. Hawn, W. Conrad Liles Ivyspring International Publisher 5 1 1 8 2008-1-4 Research Paper