We identified eight loci where CNV is significantly associated with HCC. Six of these appear to be germline CNVs. The other two, however, involve T-cell receptor

loci, which APO866 are known to undergo recombination in peripheral blood lymphocytes, the source of DNA for our study. Of the six loci showing germline CNV, the one exhibiting the strongest association with HCC is a small region of chromosome 1p36.33 that contains no known or predicted genes. In this case, low copy number correlates with increased risk for both HCC (unadjusted P = 5.94 × 10−16 for Stage 1, P = 1.11 × 10−10 for Stage 2; Table 1) and LC (unadjusted P = 6.03 × 10−9 for combined Stage 1 and Stage 2; Table 2). The five other regions for which CNV is associated INK 128 clinical trial with HCC contain the genes KNG1 (3q27.3); C4orf29 and LARP2 (4q28.2); ALDH7A1, PHAX, C5orf48, and LMNB1 (5q23.2); SRPK2 and PUS7 (7q22.2); and TMPO (12q23.1). Low copy number at all five of these loci is more

frequent in controls than HCC patients (Table 1). We observed no statistically significant association between CNV at these five loci and LC (Table 2). Additionally, none of these loci show significant differences between LC and HCC. Among the loci showing association of CNV with HCC, the strongest association is seen at the TRG@ and TRA@. In both cases low copy number is more frequent in controls than cases. In HCC versus controls, TRG@ shows an unadjusted P of 3.16 × 10−21 in the Stage 1 training MCE公司 set and P = 1.85 × 10−28 in the Stage 2 testing set; TRA@ has an unadjusted P = 1.94 × 10−16 in Stage 1 and P = 6.24 × 10−28 in Stage 2 (Table 1). We validated these findings using an independent platform by performing a TaqMan assay (t test P = 2.86 × 10−18 for TRA@; P = 3.56 × 10−26 for TRG@ for combined Stage 1 and Stage 2 samples; Supporting Table S9). CNV at the TRG@ and TRA@ loci also differs significantly between control and LC individuals (unadjusted P of 5.66 × 10−12 and 3.17 × 10−13, respectively, in combined Stage 1 and Stage 2 samples; Table 2). As is seen in HCC, low copy

number is more frequent in control than LC individuals. To confirm our proposal that the observed CNV at TRA@ and TRG@ reflects somatic genomic rearrangement at these loci that occurs in normal T lymphocytes, we inspected publicly accessible CNV data at these T-cell receptor loci in B cells. Because B cells do not exhibit TCR rearrangement, they should be diploid at the TRA@ and TRG@ loci. As expected, neither locus shows CNV in publicly accessible HapMap genotype data, which were generated using DNA isolated from B-cell lymphoblastoid cell lines established at the Centre d’Etude du Polymorphisme Humain (CEPH).17 We observe no significant association between CNV at the T-cell receptor loci and hepatitis virus status in the cases where viral status is known in the current study population (Supporting Table S4).

We identified eight loci where CNV is significantly associated with HCC. Six of these appear to be germline CNVs. The other two, however, involve T-cell receptor

loci, which AZD9668 supplier are known to undergo recombination in peripheral blood lymphocytes, the source of DNA for our study. Of the six loci showing germline CNV, the one exhibiting the strongest association with HCC is a small region of chromosome 1p36.33 that contains no known or predicted genes. In this case, low copy number correlates with increased risk for both HCC (unadjusted P = 5.94 × 10−16 for Stage 1, P = 1.11 × 10−10 for Stage 2; Table 1) and LC (unadjusted P = 6.03 × 10−9 for combined Stage 1 and Stage 2; Table 2). The five other regions for which CNV is associated VX-809 in vitro with HCC contain the genes KNG1 (3q27.3); C4orf29 and LARP2 (4q28.2); ALDH7A1, PHAX, C5orf48, and LMNB1 (5q23.2); SRPK2 and PUS7 (7q22.2); and TMPO (12q23.1). Low copy number at all five of these loci is more

frequent in controls than HCC patients (Table 1). We observed no statistically significant association between CNV at these five loci and LC (Table 2). Additionally, none of these loci show significant differences between LC and HCC. Among the loci showing association of CNV with HCC, the strongest association is seen at the TRG@ and TRA@. In both cases low copy number is more frequent in controls than cases. In HCC versus controls, TRG@ shows an unadjusted P of 3.16 × 10−21 in the Stage 1 training 上海皓元 set and P = 1.85 × 10−28 in the Stage 2 testing set; TRA@ has an unadjusted P = 1.94 × 10−16 in Stage 1 and P = 6.24 × 10−28 in Stage 2 (Table 1). We validated these findings using an independent platform by performing a TaqMan assay (t test P = 2.86 × 10−18 for TRA@; P = 3.56 × 10−26 for TRG@ for combined Stage 1 and Stage 2 samples; Supporting Table S9). CNV at the TRG@ and TRA@ loci also differs significantly between control and LC individuals (unadjusted P of 5.66 × 10−12 and 3.17 × 10−13, respectively, in combined Stage 1 and Stage 2 samples; Table 2). As is seen in HCC, low copy

number is more frequent in control than LC individuals. To confirm our proposal that the observed CNV at TRA@ and TRG@ reflects somatic genomic rearrangement at these loci that occurs in normal T lymphocytes, we inspected publicly accessible CNV data at these T-cell receptor loci in B cells. Because B cells do not exhibit TCR rearrangement, they should be diploid at the TRA@ and TRG@ loci. As expected, neither locus shows CNV in publicly accessible HapMap genotype data, which were generated using DNA isolated from B-cell lymphoblastoid cell lines established at the Centre d’Etude du Polymorphisme Humain (CEPH).17 We observe no significant association between CNV at the T-cell receptor loci and hepatitis virus status in the cases where viral status is known in the current study population (Supporting Table S4).

All six known tyrosine sulphations of FVIII were confirmed in N8. Two N-linked glycosylations are present in the A3 and C1 domain of the light chain and two in the A1 domain of the heavy chain. The majority of the N-linked glycans are sialylated bi-antennary structures. An O-glycosylation site is present in the B-domain linker region. This site was glycosylated with a doubly sialylated GalNAc-Gal structure in approximately 65% of the product. In conclusion, the present data 3-deazaneplanocin A concentration show that N8 is a

pure and well-characterized FVIII product with biochemical properties that equal other FVIII products. “
“Haemophilia is a complex disease to manage. Home-based management of haemophilia has placed greater responsibility for disease management on individuals with haemophilia, heightening the individual’s need for knowledge, particularly among individuals with severe haemophilia. The aim of this study was to identify and understand the knowledge needs and gaps of Canadian men with severe haemophilia

from the perspectives of health care providers. A qualitative approach was undertaken. Data were collected using semi-structured focus groups and interviews with health care providers from Haemophilia Treatment Centres (HTCs) across Canada; data were analysed using thematic analysis. Three focus groups and two interviews were conducted; 13 individuals participated in this study. Health care providers identified the following areas of knowledge required by men with severe haemophilia: disease pathology, causes and consequences of bleeds, bleed prevention, recognition, treatment, how and when to access support, PD0325901 activity selection and risk reduction, benefits of exercise, genetic inheritance patterns, impact on career selection, travel and ageing. Knowledge gaps and challenges to knowledge provision were highlighted. In addition, providers emphasized the influences of timing, rapport and context on

readiness to receive and assimilate information and recommended tailoring education to the individual and creating a developmental curriculum and knowledge assessment tool. Provision and uptake of disease knowledge is essential to patient self-management. To effectively receive, retain and assimilate information, individuals with severe 上海皓元医药股份有限公司 haemophilia require the right information, from the right source, at the right time. Education should be tailored to the needs of the individual, provided throughout the lifespan. “
“To explore the experiences and educational needs of parents learning to use an Implanted Central Venous Access Device (IVAD) to administer clotting factor to their child with haemophilia. Parents of children with haemophilia who had learnt to administer clotting factor via IVAD attended focus groups to discuss their experiences of the learning process. Data were transcribed and analyzed thematically. Parents described distress and trauma in dealing with the diagnosis and treatment of their child’s haemophilia.

All six known tyrosine sulphations of FVIII were confirmed in N8. Two N-linked glycosylations are present in the A3 and C1 domain of the light chain and two in the A1 domain of the heavy chain. The majority of the N-linked glycans are sialylated bi-antennary structures. An O-glycosylation site is present in the B-domain linker region. This site was glycosylated with a doubly sialylated GalNAc-Gal structure in approximately 65% of the product. In conclusion, the present data Selleckchem Romidepsin show that N8 is a

pure and well-characterized FVIII product with biochemical properties that equal other FVIII products. “
“Haemophilia is a complex disease to manage. Home-based management of haemophilia has placed greater responsibility for disease management on individuals with haemophilia, heightening the individual’s need for knowledge, particularly among individuals with severe haemophilia. The aim of this study was to identify and understand the knowledge needs and gaps of Canadian men with severe haemophilia

from the perspectives of health care providers. A qualitative approach was undertaken. Data were collected using semi-structured focus groups and interviews with health care providers from Haemophilia Treatment Centres (HTCs) across Canada; data were analysed using thematic analysis. Three focus groups and two interviews were conducted; 13 individuals participated in this study. Health care providers identified the following areas of knowledge required by men with severe haemophilia: disease pathology, causes and consequences of bleeds, bleed prevention, recognition, treatment, how and when to access support, http://www.selleckchem.com/products/bmn-673.html activity selection and risk reduction, benefits of exercise, genetic inheritance patterns, impact on career selection, travel and ageing. Knowledge gaps and challenges to knowledge provision were highlighted. In addition, providers emphasized the influences of timing, rapport and context on

readiness to receive and assimilate information and recommended tailoring education to the individual and creating a developmental curriculum and knowledge assessment tool. Provision and uptake of disease knowledge is essential to patient self-management. To effectively receive, retain and assimilate information, individuals with severe MCE公司 haemophilia require the right information, from the right source, at the right time. Education should be tailored to the needs of the individual, provided throughout the lifespan. “
“To explore the experiences and educational needs of parents learning to use an Implanted Central Venous Access Device (IVAD) to administer clotting factor to their child with haemophilia. Parents of children with haemophilia who had learnt to administer clotting factor via IVAD attended focus groups to discuss their experiences of the learning process. Data were transcribed and analyzed thematically. Parents described distress and trauma in dealing with the diagnosis and treatment of their child’s haemophilia.

e., TNF-α, MCP-1, and IL-18). In addition, adipose tissue from

these mice had up-regulated expression of adiponectin, PPARγ, and IRS-1 in parallel with reduced JNK phosphorylation, suggesting an insulin-sensitizing effect of the lack of 5-LO in this tissue. Furthermore, hepatocytes isolated from ApoE−/− mice lacking 5-LO were more resistant to damage. Interestingly, 5-LO products (i.e., LTB4, LTD4, and 5-HETE) made hepatocytes more susceptible to TNF-α–induced apoptosis through mechanisms related to the suppression of NF-κB activity. To our knowledge, this is the first study reporting the impact of 5-LO products on hepatocyte survival and the implication of 5-LO in the progression of hepatic inflammation in metabolic liver disease. The initial stages of NAFLD are characterized by simple steatosis or fatty liver with no detectable inflammation followed RXDX-106 by the combination of steatosis with inflammation, which is known as steatohepatitis.1, 2 The findings obtained in our study with ApoE−/− mice clearly dissociate steatosis and inflammation in

the liver. Indeed, compared with ApoE−/− mice, we found that ApoE−/−/5-LO−/− mice showed reduced hepatic inflammation but a comparable degree of hepatic steatosis, suggesting www.selleckchem.com/products/PF-2341066.html that hepatic inflammation can develop independently of steatosis. Consistent with this finding, striking changes were observed in the expression of inflammatory genes in the livers of ApoE−/−/5-LO−/− mice. Among these genes, we detected a reduction in MCP-1, which is a potent chemoattractant protein that contributes to the maintenance of the inflammatory infiltrate during liver injury, and its expression has been shown to be elevated in patients with chronic viral hepatitis and in experimental models of liver injury.30, 31 We also detected medchemexpress a significant reduction in TNF-α, considered one of the main cytokines involved

in hepatocellular damage,32 and in IL-18, which causes liver injury by induction of Fas-dependent hepatocyte apoptosis.33 Together, our findings indicate that 5-LO is an important factor in the transition from steatosis to steatohepatitis. Our data also provide evidence that 5-LO regulates adipose tissue biology in ApoE−/− mice. Indeed, the absence of 5-LO in these mice was associated with an increased expression of adiponectin in parallel with a decrease in MCP-1 and IL-6 in adipose tissue. Whereas adiponectin appears to induce beneficial effects in NAFLD by decreasing liver injury and attenuating fibrogenesis,34, 35 MCP-1 and IL-6 are two regulatory adipokines that work as an interface between metabolism and inflammation.

She has restarted treatment with warfarin. Varices are prominent portosystemic collateral veins that develop in patients with portal hypertension. Varices in the lower esophagus are the most frequent site

of bleeding but varices can also bleed in a variety of other sites including the stomach, duodenum and rectum and from operative sites such as abdominal stomas. When portal hypertension is caused by portal vein thrombosis, most patients have prominent collaterals around the portal vein with more frequent varices involving the bile duct, gallbladder and duodenum. For duodenal varices, management issues arise with active bleeding or a previous history of bleeding. Treatment options AZD6738 concentration include interventional radiologic procedures (portosystemic shunt and/or embolization) and various surgical shunt procedures. Contributed by “
“Anorectal pain may rise from a variety of pathologies including proctologic, urologic and gynecologic disorders,

or may be of NVP-BGJ398 cost functional origin when no specific cause is identified. The most common organic causes are anal fissure, abscesses, fistulas and thrombosed hemorrhoids. The most common functional causes include proctalgia fugax and levator ani syndrome. A careful history of the pattern of pain and its relation with bowel movements usually leads to the correct diagnosis. Pruritus ani is a very common symptom with a wide spectrum of etiologies including anatomic, dermatologic, infectious, systemic and other conditions. Diagnosis requires a complete and accurate evaluation as in the majority of the patients a pathologic anal or anorectal cause can be identified. “
“In a recent,

interesting article, Musso et al.,1 reviewing reports of randomized controlled trials, comprehensively assessed the efficacy of proposed treatments for nonalcoholic fatty liver disease (NAFLD). The authors concluded that well-designed randomized controlled trials are needed to assess MCE公司 the efficacy of proposed treatments with respect to patient-oriented outcomes contributing to the burden of NAFLD, such as cardiovascular disease (CVD).1 Evidence that has accumulated in recent years supports a potential link between NAFLD and an increased risk of CVD,2, 3 and this has prompted me to add a suggestion to be taken into consideration when future trials are designed to improve treatment efficacy: the employment of a dual-functional agent to combat NAFLD and prevent CVD. For instance, as one of the most important lipid-soluble antioxidants for humans, vitamin E has shown promising results for the treatment of fatty liver diseases, as indicated by many clinical trial studies.4, 5 A recent, rigorous trial that was reported in the New England Journal of Medicine4 found that supplementation with the natural form of vitamin E, in comparison with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis, the most extreme form of NAFLD.

The objective of this systematic review was to evaluate the effect of adjuvant antiviral therapy on recurrence and survival after curative treatment of HCC. We conducted an extensive search strategy. All randomized controlled trials comparing adjuvant antiviral therapy versus placebo or no treatment were considered for this review. Results were expressed as hazard ratio for time-to-event

outcomes with 95% confidence intervals using RevMan 5. We included nine trials (three of low risk of bias and six of unclear risk of bias) with 954 patients. All the included studies used conventional interferon (IFN) as adjuvant antiviral therapy; none of them used pegylated IFN or nucleoside analogs. There were significant improvements for recurrence-free survival and overall survival in the adjuvant IFN group Y 27632 compared with the control group. Subgroup analysis also showed a significant selleck chemicals llc difference favoring IFN therapy in hepatitis C virus (HCV)-related HCC patients, but for hepatitis B virus (HBV)-related patients, the difference failed to reach statistical significance. A dose reduction was needed in 28.3% of patients and discontinuation of IFN therapy happened in 8.2% of patients due to moderate to severe side-effects. Our study suggested potential benefits of adjuvant IFN therapy following curative treatment of HCC, especially for HCV-related HCC. Further high-quality randomized controlled trials of more effective

adjuvant antiviral regimens, either used alone or in combination, for virus-related HCC, especially HBV-related HCC, are needed. “
“Acute liver injury is manifested by different degree of hepatocyte necrosis and may recover via the process of hepatocyte regeneration once the injury is discontinued. Most of the liver injury is associating with inflammatory cytokines.

Resveratrol (RSV) is a natural phytoalexin with powerful anti-inflammatory effects. The effects of RSV on cellular factors mediating liver damage and medchemexpress regeneration in acute carbon tetrachloride (CCl4) liver injury were investigated. RSV decreased alanine aminotransferase, aspartate aminotransferase, necrosis, and 4-hydroxynonenal in the CCl4-injured liver. RSV decreased hepatocyte apoptosis by reducing caspase 8 and caspase 3 but not Bax and Bcl-xL. RSV reduced Kupffer cells recruitment, the expressions of tumor necrosis factor-α and interleukin-6, but not interleukin-10. RSV lowered the numbers of anti-5-bromon-2′-deoxyuridine and anti-Ki67-positive hepatocytes. Hepatic hepatocyte growth factor, c-Met and transforming growth factor-α expressions were reduced by RSV, while transforming growth factor-β1 and hepatic stellate cells activation were not changed. RSV reduced the injury-induced CXCL10 elevations in serum and liver in vivo. Besides, RSV inhibited CXCL10 release from CCl4-injured hepatocytes in vitro. In contrast, recombinant CXCL10 improved the viability of CCl4-injured hepatocytes. RSV therapy can be beneficial for acute toxic liver injury.

Patients were further instructed to call the principal investigator when necessary. The intensity of symptoms was quantified by means of visual analogue scales (VASs) in the morning and in the evening. The pruritus VAS score varied from score 0 (no pruritus) to 10 (severe pruritus). Fatigue and quality of sleep were evaluated with comparable VAS scores. Patients were asked to begin completing the pruritus VAS scores 7 days before the actual start of treatment (day 0). The severity Venetoclax mw of pruritus was

further quantified by open categorized questions and by descriptions of the nature and extent of cutaneous scratch lesions, which were classified as follows: (1) excoriations (mild), (2) plaques (moderate), (3) nodules (severe), or (4) indifferent scars. Additionally, with identical cameras with the same settings, photographs were taken from the

front and back of the extremities and the trunk before treatment and at the end of treatment. The severity of skin lesions was scored on the basis of these photographs U0126 mw by an experienced dermatologist (H.B.T.) who was blinded with respect to the treatment allocation and sequence of photographs. The participants completed two validated quality-of-life scores (Short Form 36 and Liver Disease Symptom Index 2.0) before and after treatment.16, 17 Finally, laboratory investigations, including measurements of the total serum bile acid, total bilirubin, albumin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels, were performed before and at the end of treatment. Possible adverse events were assessed after 7 and 21 days of treatment. When patients were using ursodeoxycholic acid, this treatment was continued. To prevent interference with the absorption of ursodeoxycholic acid and other drugs including levothyroxine, glyburide, and oral contraceptives, a minimal interval of 4 hours between the intake of the

study medication and these drugs was advised. Antipruritic drugs other than the study medication were stopped with a washout period of at least 3 weeks. However, patients were allowed to continue rifampicin and naltrexone at a stable dose if they medchemexpress felt these agents were of (some) benefit. No other antipruritic drug was allowed during the trial when patients experienced worsening of pruritus. The predefined primary endpoint of this study was the proportion of patients per group with at least a 40% reduction of pruritus based on VAS scores; this was based on a comparison of the mean scores on days 18, 19, and 20 with the mean scores on days −2, −1, and 0. Secondary endpoints were an improvement in quality-of-life scores and a reduction in the severity of scratch lesions after 21 days in comparison with pretreatment scores. The power calculation (Fisher’s exact test) was based on the primary outcome of a 40% reduction in the severity of pruritus. On the basis of a study of Mayo et al.

The numbers of miRNAs continues to

grow, and additional mRNAs and candidate genes regulated by them continue to be identified. With respect to the liver, miR-122 was identified as the most abundant miRNA expressed in hepatocytes (accounting for ≈70% of total miRNAs) and shown to have major effects on several enzymes of cholesterol metabolism.41, 42 Unexpectedly, miR-122 was also shown to be required for HCV expression,19, 43 at least in cell culture systems. Fostamatinib More recent work has shown that the effects of miR-122 depend upon the context and location of its cognate seed sequence binding sites. The sites in the 5′-UTR are mostly associated with up-regulation of expression, whereas those in the 3′-UTR are mostly associated with repression of expression.44 The present study adds miR-196 as a down-regulator of HCV expression (Figs. 6 and and an attractive candidate as new therapeutic agents for chronic HCV infection. Our study has limitations. Compound Library datasheet Effects of miR-196 on, Bach1, HMOX1, and HCV thus far have been shown only in cell culture models, and the suppression of HCV expression has been moderate, not extremely high. The field of HCV research has been stymied by the lack of simple and robust animal models. Among nonhuman

species, only chimpanzees have thus far been capable of being infected with HCV, and the disease in them is generally relatively mild. They are also extraordinarily difficult medchemexpress and expensive to maintain. Recently, murine models have been developed, based on immunodeficient

animals into which human hepatocytes are implanted without rejection and then infected with the hepatitis C virus.45, 46 Another recent model has been able to establish this in non-immunodeficient mice in which the host animal hepatocytes undergo necrosis and apoptosis and can be rescued with human hepatocytes.47 Thus, overexpression of a combination of miR-196 and other selected miRNAs in order to decrease the viral output further in cell cultures and murine models are currently under study in our laboratory. In conclusion, we demonstrate functional miR-196 binding sites in the 3′-UTR of Bach1, which lead to down-regulation of Bach1 gene expression, up-regulation of HMOX1 gene expression, and down-regulation of HCV expression. These findings add to the growing panoply of miRNAs that influence expression of genes and proteins of the hepatitis C virus and of HMOX1, a key cytoprotective enzyme. They suggest potential new additional therapies for chronic HCV infection and, perhaps, for other diseases characterized by increased oxidative stress. We thank Dr. Rolf Renne (University of Florida, Gainesville, FL) for the generous gift of luciferase reporter construct pGL3-Bach1 and Dr. Bryan R. Cullen (Duke University, Durham, NC) for providing pLSV40-Rluc, pLSV40-GL3, and pLSV40-GL3/Bach1 reporter vectors. We are grateful to Dr.

The numbers of miRNAs continues to

grow, and additional mRNAs and candidate genes regulated by them continue to be identified. With respect to the liver, miR-122 was identified as the most abundant miRNA expressed in hepatocytes (accounting for ≈70% of total miRNAs) and shown to have major effects on several enzymes of cholesterol metabolism.41, 42 Unexpectedly, miR-122 was also shown to be required for HCV expression,19, 43 at least in cell culture systems. NVP-BEZ235 datasheet More recent work has shown that the effects of miR-122 depend upon the context and location of its cognate seed sequence binding sites. The sites in the 5′-UTR are mostly associated with up-regulation of expression, whereas those in the 3′-UTR are mostly associated with repression of expression.44 The present study adds miR-196 as a down-regulator of HCV expression (Figs. 6 and and an attractive candidate as new therapeutic agents for chronic HCV infection. Our study has limitations. Fostamatinib purchase Effects of miR-196 on, Bach1, HMOX1, and HCV thus far have been shown only in cell culture models, and the suppression of HCV expression has been moderate, not extremely high. The field of HCV research has been stymied by the lack of simple and robust animal models. Among nonhuman

species, only chimpanzees have thus far been capable of being infected with HCV, and the disease in them is generally relatively mild. They are also extraordinarily difficult 上海皓元医药股份有限公司 and expensive to maintain. Recently, murine models have been developed, based on immunodeficient

animals into which human hepatocytes are implanted without rejection and then infected with the hepatitis C virus.45, 46 Another recent model has been able to establish this in non-immunodeficient mice in which the host animal hepatocytes undergo necrosis and apoptosis and can be rescued with human hepatocytes.47 Thus, overexpression of a combination of miR-196 and other selected miRNAs in order to decrease the viral output further in cell cultures and murine models are currently under study in our laboratory. In conclusion, we demonstrate functional miR-196 binding sites in the 3′-UTR of Bach1, which lead to down-regulation of Bach1 gene expression, up-regulation of HMOX1 gene expression, and down-regulation of HCV expression. These findings add to the growing panoply of miRNAs that influence expression of genes and proteins of the hepatitis C virus and of HMOX1, a key cytoprotective enzyme. They suggest potential new additional therapies for chronic HCV infection and, perhaps, for other diseases characterized by increased oxidative stress. We thank Dr. Rolf Renne (University of Florida, Gainesville, FL) for the generous gift of luciferase reporter construct pGL3-Bach1 and Dr. Bryan R. Cullen (Duke University, Durham, NC) for providing pLSV40-Rluc, pLSV40-GL3, and pLSV40-GL3/Bach1 reporter vectors. We are grateful to Dr.