bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative genomics identifies genes mediating cardiotoxicity in the embryonic zebrafish heart
Authors: Chen Jing , Carney Sara A. , Peterson Richard E. , Heideman Warren
Published: January 2008

Retinoic acid (RA) and 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) activate distinct ligand-dependent transcription factors, and both cause cardiac malformation and heart failure in zebrafish embryos. We hypothesized that they cause this response by hyperactivating a common set of genes critical for heart development. To test this, we used microarrays to measure transcript changes in hearts isolated from zebrafish embryos 1, 2, 4, and 12 h after exposure to 1 μM RA. We used hierarchical clustering to compare the transcriptional responses produced in the embryonic heart by RA and TCDD. We could identify no early responses in common between the two agents. However, at 12 h both treatments produced a dramatic downregulation of a common cluster of cell cycle progression genes, which we term the cell cycle gene cluster. This was associated with a halt in heart growth. These results suggest that RA and TCDD ultimately trigger a common transcriptional response associated with heart failure, but not through the direct activation of a common set of genes. Among the genes rapidly induced by RA was Nr2F5, a member of the COUP-TF family of transcriptional repressors. We found that induction of Nr2F5 was both necessary and sufficient for the cardiotoxic response to RA.
TAp73α Increases p53 Tumor Suppressor Activity in Thyroid Cancer Cells via the Inhibition of Mdm2-Mediated Degradation
Authors: Malaguarnera Roberta , Vella Veronica , Pandini Giuseppe , Sanfilippo Mariangela , Pezzino Vincenzo , Vigneri Riccardo , Frasca Francesco
Published: January 2008

p53 family proteins include p53 tumor suppressor, p63, and p73. Despite the high similarity in structure and function with p53, p63, and p73 function in tumor suppression is still controversial. Here, we show that TAp73α, a transcriptionally active p73 isoform, is able to synergize p53 tumor suppressor function in thyroid cancer cells. Indeed, depletion of p73 by small interfering RNA in thyroid cancer cells resulted in a reduced transcriptional activity of p53. Ectopic coexpression of both p53 and TAp73α in thyroid cancer cells resulted in increased transcription and tumor suppressor function compared with p53 or TAp73α alone, as well as in increased p53 protein levels. The enhancing effect of TAp73α on p53 activity is Mdm2 dependent because it is prevented by Mdm2 depletion by small interfering RNA. At least two mechanisms may explain the interference of TAp73α with p53 function. First, in thyroid cancer cells, TAp73α inhibits the effect of p53 on Mdm2 induction by antagonizing p53 at the Mdm2 promoter level. Second, a TAp73α mutant (G264W), which is devoid of DNA binding capability, is still able to increase p53 protein levels by competing with p53 for Mdm2 protein binding. Taken together, these results indicate that in thyroid cancer cells, TAp73α is able to increase p53 protein level and function by interfering with Mdm2-mediated p53 degradation. These results may be useful for designing gene therapies aimed at restoring a normal p53 function in thyroid cancer cells. (Mol Cancer Res 2008;6(1):64–77)
Sensitivity of Normal, Paramalignant, and Malignant Human Urothelial Cells to Inhibitors of the Epidermal Growth Factor Receptor Signaling Pathway
Authors: MacLaine Nicola J. , Wood Michelle D. , Holder Julie C. , Rees Robert W. , Southgate Jennifer
Published: January 2008

Bladder cancer evolves via the accumulation of numerous genetic alterations, with loss of p53 and p16 function representing key events in the development of malignant disease. In addition, components of the epidermal growth factor receptor (EGFR) signaling pathway are frequently overexpressed, providing potential chemotherapeutic targets. We have previously described the generation of “paramalignant” human urothelial cells with disabled p53 or p16 functions. In this study, we investigated the relative responses of normal, paramalignant, and malignant human urothelial cells to EGFR tyrosine kinase inhibitors (PD153035 and GW572016), a mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) kinase (MEK) inhibitor (U0126), and a phosphatidylinositol 3-kinase inhibitor (LY294002). The proliferation of normal human urothelial cells was dependent on signaling via the EGFR and MEK pathways and was abolished reversibly by inhibitors of EGFR or downstream MEK signaling pathways. Inhibitors of phosphatidylinositol 3-kinase resulted in only transient cytostasis, which was most likely mediated via cross-talk with the MEK pathway. These responses were maintained in cells with disabled p16 function, whereas cells with loss of p53 function displayed reduced sensitivity to PD153035 and malignant cell lines were the most refractory to PD153035 and U0126. These results indicate that urothelial cells acquire insensitivity to inhibitors of EGFR signaling pathways as a result of malignant transformation. This has important implications for the use of EGFR inhibitors for bladder cancer therapy, as combination treatments with conventional chemotherapy or radiotherapy may protect normal cells and enable better selective targeting of malignant cells. (Mol Cancer Res 2008;6(1):53–63)
Histone Modifications at the ABCG2 Promoter following Treatment with Histone Deacetylase Inhibitor Mirror Those in Multidrug-Resistant Cells
Authors: To Kenneth K.W. , Polgar Orsolya , Huff Lyn M. , Morisaki Kuniaki , Bates Susan E.
Published: January 2008

ABCG2 is a ubiquitous ATP-binding cassette transmembrane protein that is important in pharmacology and may play a role in stem cell biology and clinical drug resistance. To study the mechanism(s) regulating ABCG2 expression, we used ChIP to investigate the levels of acetylated histone H3, histone deacetylases (HDAC), histone acetyltransferases, and other transcription regulatory proteins associated with the ABCG2 promoter. Following selection for drug resistance and the subsequent overexpression of ABCG2, an increase in acetylated histone H3 but a decrease in class I HDACs associated with the ABCG2 promoter was observed. Permissive histone modifications, including an increase in histone H3 lysine 4 trimethylation (Me3-K4 H3) and histone H3 serine 10 phosphorylation (P-S10 H3), were observed accompanying development of the resistance phenotype. These changes mirrored those in some cell lines treated with a HDAC inhibitor, romidepsin. A repressive histone mark, trimethylated histone H3 lysine 9 (Me3-K9 H3), was found in untreated parental cells and cells that did not respond to HDAC inhibition with ABCG2 up-regulation. Interestingly, although all five studied cell lines showed global histone acetylation and MDR1 up-regulation upon HDAC inhibition, only those cells with removal of the repressive mark, and recruitment of RNA polymerase II and a chromatin remodeling factor Brg-1 from the ABCG2 promoter, showed increased ABCG2 expression. In the remaining cell lines, HDAC1 binding in association with the repressive Me3-K9 H3 mark apparently constrains the effect of HDAC inhibition on ABCG2 expression. These studies begin to address the differential effect of HDAC inhibitors widely observed in gene expression studies. (Mol Cancer Res 2008;6(1):151–64)
The Oncoprotein SS18-SSX1 Promotes p53 Ubiquitination and Degradation by Enhancing HDM2 Stability
Authors: D'Arcy Pádraig , Maruwge Wessen , Ryan Bríd Ann , Brodin Bertha
Published: January 2008

Mutations of the p53 gene are uncommon in synovial sarcoma, a high-grade tumor genetically characterized by the chromosomal translocation t:(X;18), which results in the fusion of SS18 with members of SSX gene family. Although implicated in tumorigenesis, the mechanisms by which SS18-SSX promotes tumor growth and cell survival are poorly defined. Here, we show that SS18-SSX1 negatively regulates the stability of the tumor suppressor p53 under basal conditions. Overexpression of SS18-SSX1 enhanced p53 ubiquitination and degradation in a manner dependent on the ubiquitin ligase activity of HDM2. The negative effect of SS18-SSX1 expression on p53 was mediated by its ability to promote HDM2 stabilization through inhibition of HDM2 autoubiquitination. Furthermore, SS18-SSX1 expression altered the induction of p53-regulated genes in response to cellular stress by abrogating the transactivation of HDM2, PUMA, and NOXA but not p21. Our data uncover a novel mechanism whereby SS18-SSX1 can negatively regulate p53 tumor-suppressive function by increasing the stability of its negative regulator HDM2 and suggest that chemical compounds that target the p53-HDM2 regulatory axis may be of therapeutic benefit for the treatment of synovial sarcoma. (Mol Cancer Res 2008;6(1):127–38)
Lack of P-Glycoprotein Expression by Low-Dose Fractionated Radiation Results from Loss of Nuclear Factor-κB and NF-Y Activation in Oral Carcinoma Cells
Authors: Shareef Mohammed Momin , Brown Brandee , Shajahan Shahin , Sathishkumar Sabapathi , Arnold Susanne M. , Mohiuddin Mohammed , Ahmed Mansoor M. , Spring Paul M.
Published: January 2008

Multidrug resistance (MDR) is associated with the overproduction of the 170-kDa transmembrane protein P-glycoprotein (MDR1) caused by transcriptional activation. However, the activity of the MDR1 promoter in response to different doses of ionizing radiation has not been investigated. In this study, two squamous cell carcinoma oral cavity cell lines, T-167 and T-409, were exposed to either a standard clinical dose of 2 Gy or low-dose fractionated radiation therapy (LDFRT), delivered as 0.5 Gy in four fractions. MDR1 gene expression and degree of cell death were assessed. Clinically relevant 2-Gy dose of radiation resulted in increased expression of MDR1 by reverse transcription-PCR and luciferase reporter assays in both cell lines (T-167 and T-409), whereas LDFRT did not. LDFRT caused enhanced apoptosis when compared with the 2-Gy dose in T-167 and T-409 cells as assessed by terminal nucleotidyl transferase–mediated nick end labeling (TUNEL) assays. Transcription of the MDR1 gene is regulated by numerous transcription factors, which include nuclear factor-κB (NF-κB), NF-Y, SP1, YB1, MEF1 (MDR1 promoter-enhancing factor 1), p53, and NF-R1. Interestingly, 2 Gy robustly induced both NF-κB and NF-Y in T-167 and T-409 cells, but did not show induction when exposed to LDFRT. Silencing the expression of the DNA binding subunit of NF-κB, p50, by small interfering RNA vector resulted in a decrease of MDR1 function by rhodamine 123 efflux assay in T167 cells exposed to 2 Gy. Together, these results provide evidence for the lack of induction of P-glycoprotein expression by LDFRT, which has important implications in combinatorial cancer therapy, including the use of LDFRT as an adjuvant for chemotherapy. (Mol Cancer Res 2008;6(1):89–98)
Transcription-Dependent Epidermal Growth Factor Receptor Activation by Hepatocyte Growth Factor
Authors: Reznik Thomas E. , Sang Yingying , Ma Yongxian , Abounader Roger , Rosen Eliot M. , Xia Shuli , Laterra John
Published: January 2008

The mechanisms and biological implications of coordinated receptor tyrosine kinase coactivation remain poorly appreciated. Epidermal growth factor receptor (EGFR) and c-Met are frequently coexpressed in cancers, including those associated with hepatocyte growth factor (HGF) overexpression, such as malignant astrocytoma. In a previous analysis of the HGF-induced transcriptome, we found that two EGFR agonists, transforming growth factor-α and heparin-binding epidermal growth factor–like growth factor (HB-EGF), are prominently up-regulated by HGF in human glioma cells. We now report that stimulating human glioblastoma cells with recombinant HGF induces biologically relevant EGFR activation. EGFR phosphorylation at Tyr845 and Tyr1068 increased 6 to 24 h after cell stimulation with HGF and temporally coincided with the induction of transforming growth factor-α (∼5-fold) and HB-EGF (∼23-fold) expression. Tyr845 and Tyr1068 phosphorylation, in response to HGF, was inhibited by cycloheximide and actinomycin D, consistent with a requirement for DNA transcription and RNA translation. Specifically, blocking HB-EGF binding to EGFR with the antagonist CRM197 inhibited HGF-induced EGFR phosphorylation by 60% to 80% and inhibited HGF-induced S-G2-M transition. CRM197 also inhibited HGF-induced anchorage-dependent cell proliferation but had no effect on HGF-mediated cytoprotection. These findings establish that EGFR can be activated with functional consequences by HGF as a result of EGFR ligand expression. This transcription-dependent cross-talk between the HGF receptor c-Met and EGFR expands our understanding of receptor tyrosine kinase signaling networks and may have considerable consequences for oncogenic mechanisms and cancer therapeutics. (Mol Cancer Res 2008;6(1):139–50)
Acquisition of Stable Inducible Up-Regulation of Nuclear Factor-κB by Tumor Necrosis Factor Exposure Confers Increased Radiation Resistance without Increased Transformation in Breast Cancer Cells
Authors: Braunstein Steve , Formenti Silvia C. , Schneider Robert J.
Published: January 2008

High-grade breast cancers are better adapted to hypoxia and more resistant to chemotherapy and radiotherapy. Constitutive activation of the transcription factor nuclear factor-κB (NF-κB) increases in breast tumors and in breast cancer cell lines, where it promotes chemoradiation resistance, in part by activation of antiapoptotic genes. The role for up-regulation of NF-κB in breast cancer progression is less clear. Here, we first show that whereas the constitutive activity of NF-κB is incrementally elevated from immortalized breast epithelial to frank transformed invasive ductal breast cancer cell lines (∼3-fold, ±0.1-fold, P < 0.05), inflammatory cytokine-inducible activity is further increased (up to 9-fold, ±0.9-fold, P < 0.05). We then show that inhibition of NF-κB activity selectively sensitizes transformed but not immortalized cells to killing by ionizing radiation or low levels of tumor necrosis factor (TNF) by up to 10-fold (±1-fold, P < 0.05) but has little effect on hypoxia-mediated cell death. Prolonged cultivation of immortalized and partially transformed cells in TNF selected for cells displaying stable constitutive and strongly inducible overexpression of NF-κB even in the absence of TNF. Stable acquisition of increased NF-κB activity conferred resistance to ionizing radiation or inflammatory cytokines, which was dependent on elevated NF-κB activity, but had no effect on transformation potential measured by in vitro and in vivo parameters. Thus, TNF and possibly other inflammatory cytokines in the tumor-stroma matrix likely select for breast cancer cells that stably overexpress NF-κB, leading to greater cancer cell survival. Greater cell survival despite increased genomic injury may permit increased acquisition of malignant genetic alterations as well as resistance to chemoradiation therapy. (Mol Cancer Res 2008;6(1):78–88)
Delayed Presentation of Isolated Complete Pancreatic Transection as a Result of Sport-Related Blunt Trauma to the Abdomen
Authors: Healey Andrew J. , Dimarakis Ioannis , Pai Madhava , Jiao Long R.
Published: January 2008

Introduction: Blunt abdominal trauma is a rare but well-recognized cause of pancreatic transection. A delayed presentation of pancreatic fracture following sport-related blunt trauma with the coexisting diagnostic pitfalls is presented. Case Report: A 17-year-old rugby player was referred to our specialist unit after having been diagnosed with traumatic pancreatic transection, having presented 24 h after a sporting injury. Despite haemodynamic stability, at laparotomy he was found to have a diffuse mesenteric hematoma involving the large and small bowel mesentery, extending down to the sigmoid colon from the splenic flexure, and a large retroperitoneal hematoma arising from the pancreas. The pancreas was completely severed with the superior border of the distal segment remaining attached to the splenic vein that was intact. A distal pancreatectomy with spleen preservation and evacuation of the retroperitoneal hematoma was performed. Discussion/Conclusion: Blunt pancreatic trauma is a serious condition. Diagnosis and treatment may often be delayed, which in turn may drastically increase morbidity and mortality. Diagnostic difficulties apply to both paraclinical and radiological diagnostic methods. A high index of suspicion should be maintained in such cases, with a multi-modality diagnostic approach and prompt surgical intervention as required.
Amicrobial Pustulosis of the Folds
Authors: Marzano Angelo V. , Ramoni Stefano , Caputo Ruggero
Published: January 2008

Background: Amicrobial pustulosis of the folds (APF) is a rare entity characterized by relapsing pustular lesions involving mainly the cutaneous folds. The disease typically occurs in the context of an autoimmune disorder and is classified within the spectrum of neutrophilic dermatoses. Objective: We studied 6 young females having APF associated with various autoimmune diseases or with the presence of serum autoantibodies and reviewed the literature, in order to give a clinical overview on this syndrome. Methods: Various routine and immunological laboratory tests, histopathological examination as well as direct and indirect immunofluorescence examinations were performed. In vitro neutrophil function was evaluated in 5 cases. We report our findings and compare our cases with those published in the literature. Results: Clinically, at least one major fold and at least one minor fold as well as the anogenital area were always involved. We documented an impaired neutrophil chemotaxis in 2 subjects, neutrophil dysfunction, thus failing to be a verifying criterion. Conclusion: APF is a neutrophilic dermatosis affecting young females, which usually shows a benign clinical behavior. Although systemic corticosteroids are the most widely used therapeutic agents, we suggest that the combination of cimetidine and ascorbic acid represents a safe alternative, which may induce long-lasting clinical remission.
Alopecia Areata Universalis Elicited during Treatment with Adalimumab
Authors: Pelivani Nedzmidin , Hassan Akmal S. , Braathen Lasse R. , Hunger Robert E. , Yawalkar Nikhil
Published: January 2008

Adalimumab is a fully humanized recombinant anti-tumour-necrosis-factor (TNF-α) monoclonal antibody which has been approved for rheumatoid arthritis, active ankylosing spondylitis, psoriatic arthritis and Crohn’s disease. We report a case of alopecia areata (AA) universalis occurring 6 months after administration of adalimumab monotherapy in a patient with a long-standing history of psoriatic arthritis and psoriasis. The diagnosis was confirmed by a scalp biopsy which showed a peribulbar infiltrate of both CD4+ and CD8+ T cells, CD1a+ dendritic cells as well as CD68+ and CD163+ macrophages. In addition, immunofluorescence staining for TNF-α was found in the mononuclear cell infiltrate. This case suggests a complex role of TNF-α in the induction of AA.
Cytokine Regulation of Intercellular Adhesion Molecule-1 Expression on Trophoblasts in Preeclampsia
Authors: Abe Emiko , Matsubara Keiichi , Oka Keizo , Kusanagi Yasuki , Ito Masaharu
Published: January 2008

In normal pregnancy, trophoblast (TR) invasion plays a crucial role in remodeling the spiral arteries to develop uteroplacental circulation. Disruption of this invasion is associated with deficient uteroplacental circulation, which can lead to the development of preeclampsia (PE) through abnormal expression of adhesion molecules in the placenta and high serum causative factors such as cytokines. We aimed to evaluate whether serum factors in PE influence intercellular adhesion molecule-1 (ICAM-1) expression of TRs. ICAM-1 expression of TRs was measured using flow cytometry and immunohistochemistry was performed to examine the localization of tumor necrosis factor-α (TNFα) and ICAM-1 in placentas derived from women with normal pregnancies and women with PE. Sera from PE patients significantly increased ICAM-1 expression on TRs compared to sera from normal pregnant women; this increase was blocked with an antibody to TNFα. TNFα also enhanced ICAM-1 expression on TRs through nuclear factor-ĸB activation. We conclude that ICAM-1 expressed on TRs is involved in PE pathogenesis and is regulated by cytokines.
Positive Association between Plasma Homocysteine Level and Chronic Kidney Disease
Authors: Shankar Anoop , Wang Jie Jin , Chua Brian , Rochtchina Elena , Flood Vicki , Mitchell Paul
Published: January 2008

Background: Increasing experimental evidence, including recently developed animal models, supports a role for homocysteine in the development of chronic kidney disease (CKD). However, relatively few clinical/epidemiological studies have examined this hypothesis in humans. We examined the relationship between plasma homocysteine level and CKD in a population-based study of older Australians. Methods: Community-based study (1992–1994) among 2,609 individuals (58.6% women), aged 49–98 years, free of clinical cardiovascular disease in the Blue Mountains region, west of Sydney, Australia. The main outcome-of-interest was CKD (n = 461), defined as estimated glomerular filtration rate of <60 ml/min/1.73 m2. Results: Higher plasma homocys- teine levels were positively associated with CKD, independent of smoking, body mass index, diabetes mellitus, hypertension, cholesterol levels, and other confounders. The multivariable odds ratio (OR; 95% confidence intervals, CI) comparing quartile 4 of plasma homocysteine (>14 µmol/l) to quartile 1 (≤9 µmol/l) was 10.44 (6.99–15.60), p-trend <0.0001. This association persisted in both men and women separately. The results were also consistent in subgroup analyses by categories of diabetes mellitus and hypertension. Conclusions: Higher plasma homocysteine levels are associated with CKD in a community-based sample of older Australians. This association appeared to be independent of diabetes mellitus and hypertension.
Treatment of a Whole Population Sample of Alzheimer’s Disease with Donepezil over a 4-Year Period: Lessons Learned
Authors: Lyle Sarah , Grizzell Moni , Willmott Sasi , Benbow Susan , Clark Michael , Jolley David
Published: January 2008

Background: In the UK it is recommended that acetylcholinesterase inhibitors be restricted to patients with moderate Alzheimer’s disease, and progress monitored within specialist clinics. Objective: To describe a cohort of patients with Alzheimer’s disease from a whole city population treated with donepezil, and to analyse outcomes over 4 years. Methods: Historical cohort design: 88 patients recruited 1997–1998, assessed at baseline with 4-year follow-up, using an agreed protocol and validated measures: survival, retention in treatment, cognition, non-cognitive symptoms, weight change, carer stress. Results: 64.7% remained on treatment beyond 6 months, 57.9% beyond 1 year and 12.5% beyond 4 years. 56% remained alive at 4 years – almost twice the number predicted. Mean MMSE score amongst patients in treatment did not deteriorate over 4 years. Survival, retention in treatment, maintenance/improvement of cognition was greater with high baseline MMSE. Non-cognitive symptoms, carer stress and weight change remained low throughout. Conclusions: A minority of people with dementia from the population (88 of potential 2,000 at outset, 11 by 4 years) received treatment. Benefits for individuals were confirmed, especially for those with mild impairment. Expenditure on medication was modest in a population context. These findings question recent guidance from the National Institute for Clinical Excellence, which would restrict therapy to patients with moderate cognitive impairment.
Response of Asymmetric Dimethylarginine to Hemodialysis-Associated Hypotension in End-Stage Renal Disease Patients
Authors: Csiky Botond , Sulyok Endre , Lakatos Orsolya , Wittmann István , Martens-Lobenhoffer Jens , Bode-Böger Stefanie M.
Published: January 2008

Aims: To define the role of asymmetric dimethylarginine (ADMA) in the control of blood pressure (BP) during hemodialysis (HD). Methods:L-Arginine, ADMA and symmetric dimethylarginine (SDMA) levels of patients with (n = 18) or without (n = 13) hypotensive episodes during HD sessions were measured before and after HD treatment by liquid chromatography-mass spectrometry. Clinical variables, laboratory parameters and underlying pathologies of end-stage renal disease (ESRD) were comparable in the groups. BP was serially recorded. Results: In patients with ESRD, plasma dimethylarginines were markedly elevated and decreased significantly by the end of the HD sessions. ADMA levels in patients having hypotensive episodes during HD were significantly higher than in those maintaining their BP (before HD: 0.62 ± 0.11 µmol/l vs. 0.71 ± 0.13 µmol/l, p = 0.04; after HD: 0.31 ± 0.11 µmol/l vs. 0.43 ± 0.11 µmol/l, p = 0.01). There was a significant inverse relationship of the minimum systolic and diastolic BP during HD to the predialysis ADMA levels (for systolic BP r = –0.50, p < 0.01; for diastolic BP r = –0.59, p < 0.01) and to the postdialysis ADMA levels (for systolic BP r = –0.49, p < 0.01; for diastolic BP r = –0.51, p < 0.005), respectively. Conclusions: It is suggested that excessive NO generation is involved in the HD-associated hypotension and induces an increase in plasma ADMA levels to prevent further fall in BP.
Hepatitis C among Predialysis Patients: Prevalence and Characteristics in a Large Cohort of Patients
Authors: Lemos Lara B. , Perez Renata M. , Lemos Marcelo M. , Draibe Sergio A. , Silva Ivonete S. , Silva Antonio Eduardo B. , Ferraz Maria Lucia G.
Published: January 2008

Background: The factors associated with hepatitis C virus (HCV) infection in predialysis patients need to be better investigated. The aims of this study were to evaluate the prevalence, risk factors, clinical, biochemical and virological characteristics of chronic HCV infection in predialysis patients. Methods: Anti-HCV antibodies were determined in a large cohort of predialysis patients. Epidemiological and laboratorial characteristics of HCV infection were evaluated in predialysis patients and this group was matched to a control group consisting of predialysis patients without viral infection (1:3) and compared in terms of risk factors and alanine aminotransferase (ALT) levels. Logistic regression analysis was applied to identify variables independently associated with chronic HCV infection. Results: A total of 1,041 patients (61% males) with a mean age of 61 ± 15 years and mean creatinine clearance of 36 ± 18 ml/min were included. Forty-one (3.9%) patients were anti-HCV positive and, of these, 39 (95%) presented viremia. Predialysis patients with HCV more frequently showed a history of blood transfusion before 1992 (66.7 vs. 10.3%; p < 0.001) and major surgeries (53.8 vs. 17.1%; p < 0.001), a higher proportion of undetermined etiology of kidney disease (43.6 vs. 17.1%; p = 0.001), and higher ALT levels (1.3 vs. 0.4 ×ULN; p < 0.001). History of blood transfusion before 1992 (p < 0.001; OR: 19), intravenous drug abuse (p = 0.002; OR: 69) and ALT levels (p < 0.001; OR: 50) were the variables that were independently associated with chronic HCV infection. The accuracy of ALT in detecting HCV infection was 92%. The most prevalent HCV genotype was 1b (48.7%) and 56.5% of patients presented high HCV viral load. Conclusion: Chronic HCV infection among predialysis patients is related to increased parenteral exposure. Elevated ALT levels suggest the need for HCV screening as part of the predialysis care since ALT seems to be a good marker of this infection.
Effect of Uncompensated Corneal Polarization on the Detection of Localized Retinal Nerve Fiber Layer Defects
Authors: Kogure Satoshi , Kohwa Hiroyuki , Tsukahara Shigeo
Published: January 2008

Purpose: To investigate the effect of corneal polarization on the detection of retinal nerve fiber layer (RNFL) defects in an artificial eye using scanning laser polarimetry. Methods: The model eye was composed of a film with a birefringence magnitude of 80 nm (single-pass retardance) in front of a plastic disc with a radial axis of birefringence, which was partially covered with a strip of black paper. The plastic disc, black paper and the film simulated the RNFL, the RNFL defect and the cornea, respectively. The model eye was located at 25 cm from the lens of the Nerve Fiber Analyzer II (NFA II) or GDx with variable corneal compensator (GDx-VCC). Using NFA II, the retardation of the laser beam was measured with/without the artificial cornea in differently simulated corneal birefringence axes that are 15° nasally downward, and 15° nasally upward. Using a GDx, the model eye with/without cornea was measured with a fixed corneal compensator (GDx-FCC) or GDx-VCC. Results: Using NFA II or GDx-FCC, there were three areas in the RNFL thickness profile where an RNFL defect was detected, undetected and reversed. The mean thickness of the RNFL defects was not different from the mean thickness of RNFL in one model eye using NFA II (p = 0.3). Using GDx-VCC, all RNFL defects were detected in all model eye settings. Conclusions: The influence of incorrect compensation of the anterior segment birefringence is significant. With an FCC, there were particular locations in the retina where the RNFL defects were not detected. The GDx-VCC is a promising tool in glaucoma diagnosis because it detects RNFL defects in any corneal setting.
The Hydrological Cycle over a Wide Range of Climates Simulated with an Idealized GCM
Authors: O’Gorman Paul A. , Schneider Tapio
Published: January 2008

A wide range of hydrological cycles and general circulations was simulated with an idealized general circulation model (GCM) by varying the optical thickness of the longwave absorber. While the idealized GCM does not capture the full complexity of the hydrological cycle, the wide range of climates simulated allows the systematic development and testing of theories of how precipitation and moisture transport change as the climate changes. The simulations show that the character of the response of the hydrological cycle to variations in longwave optical thickness differs in different climate regimes.

The global-mean precipitation increases linearly with surface temperature for colder climates, but it asymptotically approaches a maximum at higher surface temperatures. The basic features of the precipitation–temperature relation, including the rate of increase in the linear regime, are reproduced in radiative–convective equilibrium simulations. Energy constraints partially account for the precipitation–temperature relation but are not quantitatively accurate.

Large-scale condensation is most important in the midlatitude storm tracks, and its behavior is accounted for using a stochastic model of moisture advection and condensation. The precipitation associated with large-scale condensation does not scale with mean specific humidity, partly because the condensation region moves upward and meridionally as the climate warms, and partly because the mean condensation rate depends on isentropic specific humidity gradients, which do not scale with the specific humidity itself.

The local water vapor budget relates local precipitation to evaporation and meridional moisture fluxes, whose scaling in the subtropics and extratropics is examined. A delicate balance between opposing changes in evaporation and moisture flux divergence holds in the subtropical dry zones. The extratropical precipitation maximum follows the storm track in warm climates but lies equatorward of the storm track in cold climates.
Analysis of Video Disdrometer and Polarimetric Radar Data to Characterize Rain Microphysics in Oklahoma
Authors: Cao Qing , Zhang Guifu , Brandes Edward , Schuur Terry , Ryzhkov Alexander , Ikeda Kyoko
Published: January 2008

In this paper, data from three 2-dimensional video disdrometers (2DVDs) and an S-band polarimetric radar are used to characterize rain microphysics in Oklahoma. Sampling errors from the 2DVD measurements are quantified through side-by-side comparisons. In an attempt to minimize the sampling errors, a method of sorting and averaging based on two parameters (SATP) is proposed. The shape–slope (μ–Λ) relation of a constrained gamma (C-G) model is then refined for the retrieval of drop size distributions (DSDs) from polarimetric radar measurements. An adjustable term that is based on observed radar reflectivity and differential reflectivity is introduced to make the C-G DSD model more applicable. Radar retrievals using this improved DSD model are shown to provide good agreement with disdrometer observations and to give reasonable results, including in locations near the leading edge of convection where poorly sampled large drops are often observed.
Mesoscale Model Initialization of the Fourier Method for Mountain Waves
Authors: Lindeman John , Boybeyi Zafer , Broutman Dave , Ma Jun , Eckermann Stephen D. , Rottman James W.
Published: January 2008

A Fourier method is combined with a mesoscale model to simulate mountain waves. The mesoscale model describes the nonlinear low-level flow and predicts the emerging wave field above the mountain. This solution serves as the lower boundary condition for the Fourier method, which follows the waves upward to much higher altitudes and downward to the ground to examine parameterizations for the orography and the lower boundary condition. A high-drag case with a Froude number of ⅔ is presented.
Interannual Variations of the Tropical Ocean Instability Wave and ENSO
Authors: An Soon-Il
Published: January 2008

Using ocean data assimilation products, variability of eastern Pacific Ocean tropical instability waves (TIWs) and their interaction with the El Niño–Southern Oscillation (ENSO) were analyzed. TIWs are known to heat the cold tongue through horizontal advection. Conversely, variability of the cold tongue influences TIW variability (TIWV). During La Niña, TIWs are more active and contribute to anomalous warming. During El Niño, TIWs are suppressed and induce an anomalous cooling. TIWV thus acts as negative feedback to ENSO. Interestingly, this feedback is stronger during La Niña than during El Niño. To investigate this negative/asymmetric feedback, a simple parameterization for the horizontal thermal flux convergence due to TIWs was incorporated into a simple ENSO model. The model results suggested that asymmetric thermal heating associated with TIWs can explain the El Niño–La Niña asymmetry (with larger-amplitude El Niños).
Seasonal Variation of the Seychelles Dome
Authors: Yokoi Takaaki , Tozuka Tomoki , Yamagata Toshio
Published: January 2008

Using an ocean general circulation model (OGCM), seasonal variation of the Seychelles Dome (SD) is investigated for the first time. The SD is an oceanic thermal dome located in the southwestern Indian Ocean, and its influence on sea surface temperature is known to play an important role in the Indian monsoon system. Its seasonal variation is dominated by a remarkable semiannual cycle resulting from local Ekman upwelling. This semiannual nature is explained by different contributions of the following two components of the Ekman pumping: one term that is proportional to the planetary beta and the zonal wind stress and the other term that is proportional to the wind stress curl. The former is determined by the seasonal change in the zonal component of the wind stress vector above the SD; it is associated with the Indian monsoon and causes downwelling (upwelling) during boreal summer (boreal winter). The latter, whose major contribution comes from the meridional gradient of the zonal wind stress, also shows a clear annual cycle with strong upwelling during boreal summer and fall. However, it remains almost constant for 5 months from June to October, even though the zonal wind stress itself varies significantly during this period.

The above overall feature is due to the unique location of the SD; it is located between the following two regions: one is dominated by the seasonal variation in wind stress resulting from the Indian monsoon, and the other is dominated by the southeasterly trade winds that prevail throughout a year. The above uniqueness provides a novel mechanism that causes the strong semiannual cycle in the tropical Indian Ocean.
Ocean Warming and Late-Twentieth-Century Sahel Drought and Recovery
Authors: Hagos Samson M. , Cook Kerry H.
Published: January 2008

The influences of decadal Indian and Atlantic Ocean SST anomalies on late-twentieth-century Sahel precipitation variability are investigated. The results of this regional modeling study show that the primary causes of the 1980s Sahel drought are divergence and anomalous anticyclonic circulation, which are associated with Indian Ocean warming. The easterly branch of this circulation drives moisture away from the Sahel. By competing for the available moisture, concurrent tropical Atlantic Ocean warming enhanced the areal coverage of the drought. The modeled partial recovery of the precipitation in the 1990s simulations is mainly related to the warming of the northern tropical Atlantic Ocean and an associated cyclonic circulation that supplies the Sahel with moisture. Because of the changes in the scale and distribution of the forcing, the divergence associated with the continued Indian Ocean warming during the 1990s was located over the tropical Atlantic, contributing to the recovery over the Sahel. In general, the influence of SSTs on Sahel precipitation is related to their modulation of the easterly flow and the associated moisture transport. Precipitation anomalies are further enhanced by the circulation patterns associated with local convergence anomalies. These convergence anomalies and circulation patterns are sensitive to the scale and distribution of the SST anomalies and the moisture.
Hurricane Alley SST Variability in 2005 and 2006*
Authors: Chiodi Andrew M. , Harrison Don E.
Published: January 2008

The North Atlantic hurricane seasons of 2005 and 2006 were dramatically different for the Gulf Coast and eastern seaboard of the United States. The 2005 hurricane season was one of the most destructive seasons in history, whereas there was limited impact in 2006. Hurricane activity had been forecast to be above normal in 2006, but it was not. One of the conspicuous differences in environmental conditions between these two years was sea surface temperature anomaly (SSTA) over a region of the western Atlantic and Caribbean (15°–30°N, 70°–40°W), which is important for hurricane formation and intensification. SSTA was more than 1.5 standard deviations warmer during the 2005 hurricane season, but it was much less in 2006 through most of its hurricane season. The intent of this study is to determine the mechanisms responsible for this SSTA difference. It is shown that the difference can be reproduced using a simple one-dimensional (1D) ocean mixed layer model forced with surface fluxes from the NCEP–NCAR reanalysis project. It is found that there are two causes of SSTA difference over this region during July through September: the first is latent heat flux variability caused by wind speed effects, and the second is nonlinear ocean warming caused by submonthly atmospheric variability. The observed SSTA difference is reproduced by our model even though solar forcing damps the observed difference, contrary to previous hypotheses.
Asymmetry of the Indian Ocean Dipole. Part I: Observational Analysis
Authors: Hong Chi-Cherng , Li Tim , LinHo  , Kug Jong-Seong
Published: January 2008

The physical mechanism for the amplitude asymmetry of SST anomalies (SSTA) between the positive and negative phases of the Indian Ocean dipole (IOD) is investigated, using Simple Ocean Data Assimilation (SODA) and NCAR–NCEP data. It is found that a strong negative skewness appears in the IOD east pole (IODE) in the mature phase [September–November (SON)], while the skewness in the IOD west pole is insignificant. Thus, the IOD asymmetry is primarily caused by the negative skewness in IODE.

A mixed-layer heat budget analysis indicates that the following two air–sea feedback processes are responsible for the negative skewness. The first is attributed to the asymmetry of the wind stress–ocean advection–SST feedback. During the IOD developing stage [June–September (JJAS)], the ocean linear advection tends to enhance the mixed-layer temperature tendency, while nonlinear advection tends to cool the ocean in both the positive and negative events, thus contributing to the negative skewness in IODE. The second process is attributed to the asymmetry of the SST–cloud–radiation (SCR) feedback. For a positive IODE, the negative SCR feedback continues with the increase of warm SSTA. For a negative IODE, the same negative SCR feedback works when the amplitude of SSTA is small. After reaching a critical value, the cold SSTA may completely suppress the mean convection and lead to cloud free conditions; a further drop of the cold SSTA does not lead to additional thermal damping so that the cold SSTA may grow faster. A wind–evaporation–SST feedback may further amplify the asymmetry induced by the aforementioned nonlinear advection and SCR feedback processes.
Estimates of Net Atmospheric Moisture Flux Convergence over the Amazon Basin: A Comparison of Reanalysis Products
Authors: Karam Hanan N. , Bras Rafael L.
Published: January 2008

Estimates of the net convergence of atmospheric moisture flux over the Amazon Basin, [C], derived using data products from three global reanalyses, the NCEP–NCAR reanalysis (NCEP-1), the NCEP/Department of Energy reanalysis (NCEP-2), and the 40-yr ECMWF Re-Analysis (ERA-40), are compared. Two types of uncertainty in these [C] estimates are distinguished and quantified: “model-associated uncertainty,” which necessarily arises from imperfections in the numerical weather models or data assimilation algorithms, and “postprocessing uncertainty” introduced by operations performed on the original reanalysis data products to compute [C], particularly the finite-difference approximation of divergence. Model-associated uncertainty is found to overwhelm the postprocessing error. A closer look at the time series of this field extending over the period 1980–2001, and their comparison to basin-averaged precipitation and runoff data, reveals the signatures of two potential sources of model-associated errors. 1) ERA-40 estimates of [C] exhibit an artificial shift in 1987, possibly produced by the start of assimilation of Special Sensor Microwave Imager (SSM/I) data. The estimates preceding 1988 are negatively biased relative to the remaining time series, and hence subsequent analysis is limited to the 14-yr period 1988–2001. 2) NCEP-1 and NCEP-2 estimates of [C] show a negative bias over the period 1992–98, which likely originates in biased Television and Infrared Observation Satellite (TIROS) Operational Vertical Sounder (TOVS) data assimilated by these reanalyses. A measure of the random error in the [C] time series produced by each reanalysis, computed using river discharge data as reference, indicates that ERA-40 gives the most accurate estimates of net atmospheric moisture flux convergence for the aforementioned 14-yr period.
Energetics of the Global Ocean: The Role of Layer-Thickness Form Drag
Authors: Aiki Hidenori , Richards Kelvin J.
Published: January 2008

Understanding the role of mesoscale eddies in the global ocean is fundamental to gaining insight into the factors that control the strength of the circulation. This paper presents results of an analysis of a high-resolution numerical simulation. In particular, the authors perform an analysis of energetics in density space. Such an approach clearly demonstrates the role of layer-thickness form drag (residual effects of hydrostatic pressure perturbations), which is hidden in the classical analysis of the energetics of flows. For the first time in oceanic studies, the global distribution of layer-thickness form drag is determined. This study provides direct evidence to verify some basic characteristics of layer-thickness form drag that have often been assumed or speculated about in previous theoretical studies. The results justify most of the previous assumptions and speculations, including those associated with (i) the presence of an oceanic energy cycle explaining the relationship between layer-thickness form drag and wind forcing, (ii) the manner in which layer-thickness form drag removes the energy of vertically sheared geostrophic currents, and (iii) the reason why the work of layer-thickness form drag nearly balances the work of eddy-induced overturning circulation in each vertical column. However, the result of the analysis disagrees with speculation in previous studies that the layer-thickness form drag in the Antarctic Circumpolar Current is the agent that transfers the wind-induced momentum near the sea surface downward to the bottom layers. The authors present a new interpretation: the layer-thickness form drag reduces (and thereby cancels) the vertical shear resulting from the eddy-induced overturning circulation (rather than the vertical shear resulting from the surface wind stress). This interpretation is consistent with the results of the energy analysis conducted in this study.
Dry Bias in Vaisala RS90 Radiosonde Humidity Profiles over Antarctica
Authors: Rowe Penny M. , Miloshevich Larry M. , Turner David D. , Walden Von P.
Published: January 2008

Middle to upper tropospheric humidity plays a large role in determining terrestrial outgoing longwave radiation. Much work has gone into improving the accuracy of humidity measurements made by radiosondes. Some radiosonde humidity sensors experience a dry bias caused by solar heating. During the austral summers of 2002/03 and 2003/04 at Dome C, Antarctica, Vaisala RS90 radiosondes were launched in clear skies at solar zenith angles (SZAs) near 83° and 62°. As part of this field experiment, the Polar Atmospheric Emitted Radiance Interferometer (PAERI) measured downwelling spectral infrared radiance. The radiosonde humidity profiles are used in the simulation of the downwelling radiances. The radiosonde dry bias is then determined by scaling the humidity profile with a height-independent factor to obtain the best agreement between the measured and simulated radiances in microwindows between strong water vapor lines from 530 to 560 cm−1 and near line centers from 1100 to 1300 cm−1. The dry biases, as relative errors in relative humidity, are 8% ± 5% (microwindows; 1σ) and 9% ± 3% (line centers) for SZAs near 83°; they are 20% ± 6% and 24% ± 5% for SZAs near 62°. Assuming solar heating is minimal at SZAs near 83°, the authors remove errors that are unrelated to solar heating and find the solar-radiation dry bias of 9 RS90 radiosondes at SZAs near 62° to be 12% ± 6% (microwindows) and 15% ± 5% (line centers). Systematic errors in the correction are estimated to be 3% and 2% for microwindows and line centers, respectively. These corrections apply to atmospheric pressures between 650 and 200 mb.