Furthermore, the strains in kinase inhibitor Baricitinib the zero-thickness element are computed from��=1h��u��v��wT,(10)where ��u, ��v, and ��w are the relative displacements and h is the virtual element thickness. Also, note that ��u = utop ? ubot, ��v = vtop ? vbot, and ��w = wtop ? wbot.In the present study, we only focus on the localized imperfection with a uniform degeneration in Gxz, Gyz, and Ez although different degradation can be imposed on one or more of these properties by using different values of R in [Dint ]. From (5) and (10), the strains in the zero-thickness element are related to its nodal displacements via��=[Bint?]d��,(11)where[Bint?]=1h[?NN],d��=dbot��dtop��T,(12)and [Bint ]3��24 and d��24��1 are the element strain-displacement matrix and nodal displacements of the zero-thickness element, respectively.

Consequently, the element stiffness matrix of the zero-thickness interface element can be computed usingKint?=?RnBint?TDint?Bint?|J|d��?d��,(13)whereJ=[?x?��?y?��?x?��?y?��](14)is the Jacobian matrix.The stiffness matrix of the zero-thickness interface element is assembled accordingly into the local stiffness matrix of the laminate element (Figures 1(b) and 1(c)). The DOF (u, v, and w) of the nodes located at the top surface of the interface element are merged with the DOF (u, v, and w) of the nodes of top lamina. The same is performed for the DOF of the bottom surface of the interface element and those of bottom lamina.The complete local stiffness matrix of the laminate element will be then arranged accordingly to form the global stiffness matrix of the laminate.

By discretely manipulating the properties of the zero-thickness interface element, any intensity of interfacial imperfection can be prescribed at any location of the laminate. We shall next consider the effects of various perturbations of interfacial properties on the transverse deformation of a [90/0] laminated plate using such concept.3. Performance of Degenerated Laminated Composite3.1. VerificationA two-layer cross-ply composite laminate with a perfect bonding and the same laminae thickness, as shown in Figure 1(a), is modeled for verification of the present model. The fiber and the matrix of the lamina are E-Glass and Epoxy (3501-6), respectively, the composite material properties of which are shown in Table 1. In addition, the material properties of the interface layer are set similar to those of the matrix since it is customarily used in practice as the bonding component for laminates. It should be noted that the thickness of the interface layer is prescribed as one-tenth of the lamina thickness in accordance with the study conducted by Sheikh and Chakrabarti Drug_discovery [50].

3% and 56.7% only [3]. Technical developments have increased the capabilities of ultrasound since then. A recent prospective study on detection of acute pyelonephritis with contrast-enhanced ultrasound of renal transplants Rapamycin order found a sensitivity and specificity of 95% and 100% compared to contrast-enhanced T1w-MR imaging as standard of reference with excellent inter-modality agreement of K = 0.92 [13]. However, no use was made of DWI-MRI in this study. Looking closer at our data it seems that particularly in those patients with minor foci of infection or without abscess formation, the sensitivity of DWI imaging differs most from T1w and T2w imaging and clearly demonstrates foci of infection which can neither be seen nor be characterized due to too small size.

A noticeable characteristic of DWI is that in the source data with high b values (i.e., b = 800smm2) even the smallest foci of infection are displayed with high lesion-to-background contrast. This high conspicuity of inflammatory changes in combination with the assumed high sensitivity could foster the use of DWI as a primary tool for workup of complicated patients or patients with impaired renal function. As CT is increasingly often recognized as major source of radiation exposure for the general population, some experts recommend ��to replace CT use, when practical, with other options, such as magnetic resonance imaging (MRI)�� [14]. In the setting of infectious renal disease where many nononcologic patients and younger patients are being examined this is of even higher importance.

In pediatric patients the comparable radiation dose is on average 24% higher compared to the already high dose in abdominal studies in adults [15]. Especially for pediatric patients DWI-MRI of the kidneys seems Batimastat to be a perfect match combining a radiation-free examination of the abdomen with high robustness to motion as it can be acquired during continuous breathing. When applying DWI imaging to the kidneys to identify infectious foci, some caveats have to be considered. First, it is well known that chronic hydronephrosis and resulting renal fibrosis might lead to decreased ADC values of the kidneys [16, 17]. Also transplant kidneys with acute deterioration of function were found to have lower ADC values in one study than transplants with normal function [18]. Unlike the diffuse diffusion restriction seen in the latter two mentioned clinical settings, findings of infectious renal disease are often patchy and irregular and barely ever affect the entire kidney homogenously. Also, the usual clinical presentation of these patients will differ significantly. The diffusion restriction in DWI can be absolutely quantified by means of the apparent diffusion coefficient (ADC).

The figure indicates the percentage (%) of positive patients based on the detection limits of the tests. AAS = abdominal aortic surgery; …Plasma levels of cytokines, CRP, PCT, cortisol and leukocyte countsIn order to find more monitor the inflammatory process, IL-6, IL-10, CRP, PCT, and cortisol were assayed in plasma and leukocytes counted at various time points. As shown in Figure Figure5,5, significantly higher amounts of IL-6 and IL-10 were detected in the plasma of AAS patients as compared with CAS. IL-6 was detected in AAS plasma at T4 and the highest value was attained at POD1. The presence of IL-10 was maximal at T4 and high levels were maintained until POD2. In the CAS group, IL-10 and IL-6 levels were undetected in most cases. Plasma levels of CRP were measured at T1, T4, POD1, and POD2.

CRP levels started to increase at POD1 and were further increased at POD2 in both groups, but the increments were significantly higher in AAS patients than in CAS patients (Figure (Figure5).5). Similar patterns were also found in PCT levels, with the difference that the maximal value was reached at POD1 (Figure (Figure5).5). Similarly, there was a transient increase in leukocyte count at POD1 in AAS patients only, with values going back to normal at POD2 (data not shown). Plasma cortisol levels were not significantly different between AAS patients (111 �� 9 ng/ml) and CAS patients (105 �� 11 ng/ml) at T1. Both groups of patients showed a significant increase in plasma levels of cortisol at POD1 (AAS: 229 �� 44 ng/ml and CAS: 157 �� 26 ng/ml), with a tendency towards higher values for AAS patients (P = 0.

07).Figure 5Plasma levels of IL-10, IL-6, C-reactive protein and procalciton in in AAS and CAS patients. Plasma levels of cytokines, C-reactive protein (CRP), and procalcitonin (PCT) were measured at T1 (before anesthesia), T2 (before incision), T3 (before clamping), …Correlation between the levels of circulating NOD2 agonist and other parametersThe survey indicated that the inflammatory response took place after bacterial NOD2 agonist translocation. Among AAS patients, levels of circulating NOD2 agonist at T4 positively correlated with those of IL-10 at T4 and of cortisol at POD1 (r = 0.46, P = 0.04; and r = 0.55, P = 0.01, respectively). Interestingly, in AAS patients but not in CAS patients, cortisol levels at POD1 correlated with those of IL-10 at T4 and of PCT at POD1 (r = 0.59, P = 0.006; and r = 0.55, P = 0.02, respectively), Cilengitide and with the length of clamping (r = 0.45, P = 0.05). In AAS patients, the length of clamping correlated with levels of IL-6 at T4 and of PCT at POD1 (r = 0.53, P = 0.03; and r = 0.52, P = 0.02, respectively). There was no correlation between the length of clamping and levels of NOD2 agonist in the plasma.

P < 0.05 selleck screening library was considered significant. Analysis was performed using Stata (StataCorp. 2007. Stata Statistical Software: Release 10. College Station, TX: StataCorp LP) 3. Results Between July 2009 and March 2010, 87 patients were randomized for suspected appendicitis into the SPAA group (SPAAG) or an LA group (LAG). There were 46 patients in the SPAA group and 41 in the LA group. The mean age of the patients was 34,2 (17�C73) for the SPAA group and 37,7 (19�C69) for the LA group. There were 19 males and 27 females in the SPAA group and 22 males and 19 females in the LA group (Table 1). SILS Port was used in 38 patients and TriPort in 8 patients and there was no technical difference between them. In spite of technical difficulties and disorientation specially in the first few cases, the mean operative time was 40,4 minutes in the SPAA group and 35, 0 minutes in the LA group (P = 0,110).

In only 1 patient of the SPAA group, the procedure was converted to an open approach due to technical difficulties in a colonic cancer diagnosed during the surgery. Complications occurred in 2 patients, all in the SPPA group. First patient presented with acute coronary syndrome during the surgery; another young woman suffered of an acute pulmonary oedema caused by an allergic reaction to Dexketoprofen who required 5 days endotracheal intubation. The two patients presented a long hospital stay (7 days, 11 days, and 10 days resp.). All these hospital stays have been included in the mean of the postoperative stay at hospital. Drains have been used in 8 and 5 patients in each group because of the local peritonitis found (Tables (Tables22 and and33).

Table 2 Results concerning operative technique. Table 3 Postoperative results and outcomes. Oral intake was accomplished after 12,5 hours in the SPAA group and 10,7 hours in the LA group. The mean hospital stay was 44,4 hours in the SPAA group (mean 14�C264) and 34,0 hours (mean 11�C96) in the LA group. Pain was evaluated and was 2,8 in the SPAA group and 2,9 in the LA group, according to the AVS after 24 hours. The degree of satisfaction was higher in the SPAA group (7,5 versus 6,9) (P < 0.05). Same results were found for the cosmetic result (8,6 versus 7,4) (P < 0.05). At three-month followup, no hernia or other complications have appeared. 4. Discussion Many surgical research groups have developed new surgical technique called Natural Orifice Transluminal Endoscopic Surgery (NOTES) [9].

Some appendectomies have even been performed through a vaginal approach, without visible scars [10]. However, many authors consider that umbilicus a natural orifice since its origin. For this reason, many authors have reported the feasibility of LA with a transumbilical approach, especially in children [11]. Also, some studies investigated the feasibility of SPAA in study populations ranging Carfilzomib from 1 to 200 patients, and there is not a standard use of size port in the LAG [12].

6min), selleck Cisplatin which represented the mastery phase, with a decrease in OT (P = 0.0001) [14]. However there could be a phase three, a phase four, or even beyond as in our case series. His mean operative time of 223.6min for phase 2 (his defined mastery phase), which is considerably longer than typical operative times for robotic gastric bypass, makes it very likely that there are more stabilization points in operative time. For this reason, we have to comment that we could have a sample size too small to capture this stabilization phenomenon. However, times and result in terms of complications, outcomes, and results are satisfactory. When discussing robotics, all authors are concerned about time. It is clear that time can be a major issue in robotic surgery.

For this reason, we focused specifically on the set-up and docking times of the da Vinci surgical system in order to perform surgery efficiently. According to our data, trained nurses can achieve robotic setup efficiently, and docking can be conducted time effectively by the console surgeon and the first assistant. As shown previously, a trained nurse can complete robotic draping within 35 minutes while the patient is in preparation for anesthesia. The learning curve for docking has been successfully completed in our experience. Some authors have observed an increase in operating time when using the robotic system, but we believe that a learning curve is required in order to decrease time loss and potential risks [15�C17].

To our knowledge the only previous report of robotic sleeve gastrectomy mentioned the advantages of using this procedure instead of a robotic gastric bypass (RGBP) as the first step to introducing robotic surgery to a bariatric unit [18]. They suggested, and we agree, that it is always wiser to start with a less demanding procedure in order to avoid errors in the initial phases of the overall robotic learning curve. In this paper, no data were reported concerning the learning curve before attempting to undergo a RYGBP. In our experience, and according to our protocol, we perform sleeve gastrectomy in superobese patients (BMI > 50) and we consider it more suitable for initial robotic training. Using robotic assisted techniques, even in part, could be considered in RYGBP during a learning curve instead of reinforced staple line RSG. Robotic assisted RYGBP was recently performed effectively in more than 300 patients [19].

However, we suggest that RSG be completed before RYGBP Entinostat is introduced to routine clinical practice within a bariatric unit. 5. Conclusion Our early experience in RSG suggests that robotic surgery is safe, feasible, and could be an effective alternative to the conventional laparoscopic approach in bariatric surgery. Robotic surgery gives all the benefits of the laparoscopic approach, with added benefits in certain challenging surgical cases. However, we believe that bariatric surgeons should be trained in RSG before RYGBP.

Then, using the US Bureau of Labor Statistics Medical Consumer Price Index, they were standardized to 2006 dollars [5]. 2.3. Statistical Analysis Bivariate analysis of the independent Axitinib Sigma variables by outcomes was performed using ��2 tests for categorical variables and analysis of variance (ANOVA) for continuous variables. Data analysis and management were performed using SAS version 9.1 (Cary, NC, USA). Statistical significance was set at a probability value of P �� 0.05. 3. Results Of the 1,332,195 adult admissions for biliary disease in the HCUP-NIS database between 1999 and 2006, cholecystectomy was performed as the primary procedure during hospitalization in 145,675 patients aged 50�C64 years, 149,855 patients aged 65�C79 years, and 62,561 patients aged ��80 years.

In 1999, representing the start of the study period, laparoscopic cholecystectomy was performed most frequently in patients aged between 18 and 49 years (83.5%) (Figure 1). Figure 1 Yearly trends in adoption of laparoscopic cholecystectomy by age group (1999�C2006). In contrast, laparoscopic cholecystectomy was performed less often as the age groups ascended: 50�C64 years (73.2%), 65�C79 years (65.3%) and >80 years (59.7%). During each year, there was a gradual increase in patients undergoing laparoscopic surgery across all age groups. By the end of the study period in 2006, 89.2% of patients aged 18�C49 underwent laparoscopic cholecystectomy. There was also an increase in frequency for patients aged 50�C64 years (78.9%) and 65�C79 years (73.3%). Interestingly, patients aged >80 years witnessed a marked increase from 59.

7% to 72.1%. This represented the biggest increase, of 12.4%, compared to all other age groups. 3.1. Outcomes The mortality rate in the study population undergoing open cholecystectomy increased significantly with advancing age (0.5%, 1.6%, 4.0%, and 8.3%; P < 0.001) (Table 1). Table 1 Outcomes by type of cholecystectomy procedure (laparoscopic versus open). However, mortality rates were lower in all age groups with laparoscopic cholecystectomy (0.1%, 0.3%, 0.9%, and 2.3%; P < 0.001). Patients aged ��80 years experienced a significant reduction in mortality following laparoscopic cholecystectomy (open = 8.3% versus laparoscopic = 2.3%; P < 0.001) when compared to an open procedure. There was a lower overall rate of surgical complications when comparing laparoscopic to open Carfilzomib cholecystectomy between age groups. This was most evident for patients aged 65�C79 years (open = 50% versus laparoscopic = 26.3%; P < 0.001) and ��80 years (open = 61.1% versus laparoscopic = 37.2%; P < 0.001). The trend in adoption of laparoscopic cholecystectomy was also associated with lower LOS (mean days) when compared to open cholecystectomy among all age groups.

Thus, these findings indicate that the association between NF ��B and STAT3 could be dif ferent according to the cancer cell type investigated and, thus, interaction of these two molecules in terms of cancer cell metastasis in each cancer type needs to be selleck U0126 elucidated. Since the relationship between NF ��B and STAT3 path ways in gastric cancer has not been described previously, the present study performed a large scale immunohisto chemical analysis to investigate the correlation between NF ��B p65 and phospho Tyr705 STAT3 or matrix metalloproteinase 9 in 255 surgically excised human gastric carcinoma tissues. In addition, we inhibited NF ��B in gastric cancer cells by transduction with a retroviral vector containing supersuppressive mutant form of I��B and silenced STAT3 by transfection of STAT3 small interfering RNA.

Then, we evalu ated the effect of NF ��B and STAT3, alone or in combin ation, on the gastric cancer cell migration and invasion in vitro. Methods Patients and tissue array methods A total of 255 surgically resected human gastric cancer specimens were obtained from the Department of Path ology, Seoul National University College of Medicine from January 1st to June 30th, 1995 and six paraffin array blocks were prepared by Superbiochips Laborator ies, as previously described. Briefly, core tissue biopsies were taken from individual paraffin embedded gastric tumors and arranged in a new recipient paraffin block using a trephine apparatus. The staining results of the different intratumoral areas of gastric carcinomas in these tissue array blocks showed an excellent agreement.

A core was chosen from each case for analysis. We defined an adequate case as a tumor occupying more than 10% of the core area. Each block contained internal controls consisting of non neoplastic gastric mucosa from body, antrum and other areas showing intestinal metaplasia. Sections of 4 um thickness were cut from each tissue array block, deparaf finized, and rehydrated. This protocol was reviewed and approved by the Institutional Review Board of Seoul Na tional University. Immunohistochemistry Immunohistochemical staining was performed as described previously using a streptavidin peroxidase procedure after antigen retrieval using an autoclave. The primary antibodies used were anti NF ��B RelA, anti phospho Tyr705 STAT3, anti MMP9.

Immunostaining results were considered to be positive if 10% or 5% of Entinostat the neoplastic cells were stained. Cell culture SNU 638 and MKN1, which are well characterized human gastric cancer cell lines, were purchased from the Korean Cell Line Bank. Cells were cultured in RPMI1640 supplemented with 10% fetal bovine serum, 2 mg mL sodium bicarbonate, 100 U mL penicillin, and 100 ug mL streptomycin at 37 C in a humidified 95% air and 5% CO2 atmosphere. Infection with retroviral vectors expressing I��B supersuppressor The control retroviral vector MFG. EGFP. IRES.

Methods Cytokines, culture of human RA synovial fibroblasts, and chemical inhibitors TNF was purchased from R D Systems. Fibroblasts were isolated from RA synovium obtained from RA patients undergoing arthroplasty or synovectomy as described previously. For all hu man specimens used in this study, we obtained written http://www.selleckchem.com/products/Lenalidomide.html informed consent and all aspects of the study were approved by the University of Michigan Institutional Review Board. Allergies were not reported and no skin tests were performed on these RA patients. MAPK inhibitors, an NF ��B inhibitor or a JAK2 inhibitor were used at 10 uM of each inhibitor, e cept PDTC at 200 uM. All inhibitors were purchased from Calbiochem. All e periments were performed in serum free media e cept e periments for IL 18 detection.

Cell lysis and western blotting To study the effect of TNF on caspase 1 e pression, RA synovial fibroblasts were incubated with TNF in RPMI 1640 and processed, as previously described. We used a rabbit anti human caspase 1 antibody over night at 4 C and then horseradish pero idase conjugated antibody for 1 hour at room tem perature. Blots were scanned and analyzed for band intensities, as previously described. Caspase 1 activity assay RA synovial fibroblasts were pre incubated with the chemical inhibitors for 2 hours and then treated with TNF for 24 hours in serum free RPMI 1640. Cells were washed and then lysed with the lysis buffer from the caspase 1 activity assay kit. Cell lysates were centrifuged, and the supernatant was assessed. Caspase 1 activity in the supernatant was deter mined using a colorimetric caspase 1 activity assay kit.

IL 18 detection in conditioned media RA synovial fibroblasts were stimulated with TNF in RPMI 1640 with 10% fetal bovine serum supplementation for 72 hours. Conditioned me dium was collected and concentrated 10 fold using Amicon Ultra 3,000 MW concentrators from Millipore. Equal volumes of conditioned media were loaded and processed for western blotting as previously described above e cept that primary poly clonal rabbit anti human IL 18 antibody was used. ELISA for IL 18 and IL 18BP RA synovial fibroblasts were stimulated with TNF for 8 to 48 hours in RPMI with 10% FBS and conditioned medium was collected and concentrated as described above. IL 18 was assessed in conditioned media and cell lysates using an ELISA kit from Bender MedSystems.

IL 18BP was assessed Carfilzomib in condi tioned media using an ELISA kit from R D Systems. RNA e traction and quantitative real time polymerase chain reaction Following the manufacturers protocol, RNA was isolated from RA synovial fibroblasts and processed as described previously. IL 18 bioactivity The biologic activity of IL 18 was measured using human myelomonocytic KG 1 cells, as previously described. KG 1 cells, with or without mouse monoclonal anti IL 18 antibody at 1 ug ml, were dispensed into the wells of 96 well Falcon microtiter plates.

We ne t investigated the possible regulation of E cadherin, N cadherin, and vimentin e pression by SIRT1, by using siRNA oligonucleotides to knock down SIRT1 e pres sion in HOK cell lines, and found either that SIRT1 silencing clearly down regulated E cadherin e pression. Addition ally, the deletion of SIRT1 led to significantly increased N cadherin and vimentin e pression in knockdown HOK cells. A similar reciprocal relationship was ob served in the case of SIRT1 overe pression in OECM1 cells, which showed increased E cadherin e pression. Moreover, we also determined the e pression of certain mesenchymal markers important for EMT. Transfection of OSCC cells with an SIRT1 e pression vector resulted in SIRT overe pression which subsequently reduced the e pression of the mesenchy mal proteins N cadherin and vimentin.

Together, these data indicated that SIRT1 may play a role in regulating epithelial and mesenchymal protein e pression. SIRT1 represses e pression of MMP7 in OSCC cells Similar to the metastatic mechanism of other cancers, oral cancer metastasis requires an e tensive remodeling and degradation of the e tracellular matri , partially via increased e pression of matri metalloproteinases. MMP7 e pression has been significantly correlated with oral cancer metastasis and EMT, which suggests that the SIRT1 overe pression might affect MMP7 e pression in OSCCs. We thus e amined the effect of transiently e pressed SIRT1 on OSCC cell lines by using a GFP tagged SIRT1 e pressing vector. We found that MMP7 transcription and translation were significantly decreased in SIRT1 overe pressing cells compared with their levels in control cells.

We also compared the enzymatic activity of MMP7 in SIRT1 overe pressing and silencing OSCC cells. When MMP7 activity was assayed by casein zymography, the activity in the media from SIRT1 overe pressing OECM1 cells was significantly lower than that in media from mock transfected cells. In contrast, SIRT1 silen cing produced a significant increase in MMP7 activity. This activity change is probably due to the difference in the protein levels, as determined by ELISA and immunoblotting with anti MMP7 antibody. The levels of MMP7 secreted into the media of OSCC cell lines were also estimated by ELISA at 48 h after trans fection with a SIRT1 e pression vector or siSIRT1.

We found that MMP7 secretion by SIRT1 overe pressing OSCC cells was significantly suppressed as compared with secretion Entinostat by mock transfected cells. In contrast, SIRT1 silencing in oral cancer cells resulted in a significant induction of MMP7 secretion. A similar result was seen in western blot e periments, where MMP7 secretion was significantly suppressed by e ogenously produced overe pression of SIRT1 in both OSCC cell lines, whereas repression of SIRT1 by SIRT1 silencing increased MMP7 secretion.

Some reports have suggested that CCL2 could be involved in the early stages of CCR2 protein down modulation, while other studies indicate that the differentiation proc ess itself, is a major factor in the selective loss of CCR2 gene e pression. Numerous cytokines are known to be involved in monocyte activation and differentiation, now among them M CSF and IFN. M CSF is a lin eage specific hematopoetic growth factor that stimulates monocyte differentiation. The c fms proto onco gene encodes a high affinity receptor for M CSF and it has been shown that THP 1 cells e press this protein and that it is up regulated during differentiation. How ever, cells stimulated with M CSF alone for 48 hours did not lose e pression of CCR2.

Conversely, IFN alone, which is constitutively e pressed by monocyte lineage cells and which promotes matura tion of monocytes to macrophages, did significantly reduce e pression of CCR2, although the cells did not become adherent and neither did they change their mor phology. Interestingly, IFN has been demonstrated to up regulate levels of M CSF in mono cytes during maturation and when both IFN and M CSF were added, THP 1 cells did become adherent, changed their morphology and selectively lost CCR2, but not CCR1 all of which are characteristics of the mono cyte differentiation phenotype. These results are in keep ing with the studies published by Tangirala and colleagues, who reported similar phenomena in THP 1 cells. In addition, our studies also demonstrated that the regulatory effects mediated by IFN plus M CSF occurred at the level of transcription, where a significant down regulation in CCR2 promoter activity was observed.

Moreover, in the presence of staurosporine, IFN plus M CSF was unable to down regulate levels of CCR2. This result probably reflects the fact that IFN signals e ten sively through the JAK STAT pathway, and studies have suggested that staurosporine can block phosphorylation of Janus kinases. In addition, we have found two putative binding sites in the CCR2 promoter for STAT transcription factors which would further support the contention that these transcription factors may be impor tant in the regulation of IFN mediated downregulation of CCR2. Conclusion This study demonstrates that e pression of the chemokine receptor CCR2 is e quisitely correlated with monocyte maturation.

Freshly isolated monocytes e press high lev els of both CCR2 RNA and protein, whereas monocyte derived macrophages e press neither CCR2 RNA nor pro tein. Conversely, levels of the closely related chemokine receptor CCR1 remained stable and elevated throughout monocyte maturation. An analysis of the biochemical and molecular mechanisms underlying the regulated e pres sion of CCR2 revealed Anacetrapib the e istence of several signaling pathways that selectively down modulate CCR2 gene e pression during monocyte differentiation. this e pres sion was largely regulated at the level of transcription.