bluuebunny/crossref_metadata_2025 huggingface dataset:
Halocynthiaxanthin and Peridinin Sensitize Colon Cancer Cell Lines to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand
Authors: Yoshida Tatsushi , Maoka Takashi , Das Swadesh K. , Kanazawa Kazuki , Horinaka Mano , Wakada Miki , Satomi Yoshiko , Nishino Hoyoku , Sakai Toshiyuki
Published: June 2007

Carotenoids are compounds contained in foods and possess anticarcinogenic activity. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapeutics due to its ability to induce apoptosis selectively in cancer cells. However, some tumors remain tolerant to TRAIL-induced apoptosis. Therefore, it is important to develop agents that overcome this resistance. We show, for the first time, that certain carotenoids sensitize cancer cells to TRAIL-induced apoptosis. Combined treatment with halocynthiaxanthin, a dietary carotenoid contained in oysters and sea squirts, and TRAIL drastically induced apoptosis in colon cancer DLD-1 cells, whereas each agent alone only slightly induced apoptosis. The combination induced nuclear condensation and poly(ADP-ribose) polymerase cleavage, which are major features of apoptosis. Various caspase inhibitors could attenuate the apoptosis induced by this combination. Furthermore, the dominant-negative form of a TRAIL receptor could block the apoptosis, suggesting that halocynthiaxanthin specifically facilitated the TRAIL signaling pathway. To examine the molecular mechanism of the synergistic effect of the combined treatment, we did an RNase protection assay. Halocynthiaxanthin markedly up-regulated a TRAIL receptor, death receptor 5 (DR5), among the death receptor–related genes, suggesting a possible mechanism for the combined effects. Moreover, we examined whether other carotenoids also possess the same effects. Peridinin, but not alloxanthin, diadinochrome, and pyrrhoxanthin, induced DR5 expression and sensitized DLD-1 cells to TRAIL-induced apoptosis. These results indicate that the combination of certain carotenoids and TRAIL is a new strategy to overcome TRAIL resistance in cancer cells. (Mol Cancer Res 2007;5(6):615–25)
Continuous Delivery of IFN-β Promotes Sustained Maturation of Intratumoral Vasculature
Authors: Dickson Paxton V. , Hamner John B. , Streck Christian J. , Ng Catherine Y.C. , McCarville M. Beth , Calabrese Christopher , Gilbertson Richard J. , Stewart Clinton F. , Wilson Christy M. , Gaber M. Waleed , Pfeffer Lawrence M. , Skapek Stephen X. , Nathwani Amit C. , Davidoff Andrew M.
Published: June 2007

IFNs have pleiotropic antitumor mechanisms of action. The purpose of this study was to further investigate the effects of IFN-β on the vasculature of human xenografts in immunodeficient mice. We found that continuous, systemic IFN-β delivery, established with liver-targeted adeno-associated virus vectors, led to sustained morphologic and functional changes of the tumor vasculature that were consistent with vessel maturation. These changes included increased smooth muscle cell coverage of tumor vessels, improved intratumoral blood flow, and decreased vessel permeability, tumor interstitial pressure, and intratumoral hypoxia. Although these changes in the tumor vasculature resulted in more efficient tumor perfusion, further tumor growth was restricted, as the mature vasculature seemed to be unable to expand to support further tumor growth. In addition, maturation of the intratumoral vasculature resulted in increased intratumoral penetration of systemically administered chemotherapy. Finally, molecular analysis revealed increased expression by treated tumors of angiopoietin-1, a cytokine known to promote vessel stabilization. Induction of angiopoietin-1 expression in response to IFN-β was broadly observed in different tumor lines but not in those with defects in IFN signaling. In addition, IFN-β–mediated vascular changes were prevented when angiopoietin signaling was blocked with a decoy receptor. Thus, we have identified an alternative approach for achieving sustained vascular remodeling—continuous delivery of IFN-β. In addition to restricting tumor growth by inhibiting further angiogenesis, maturation of the tumor vasculature also improved the efficiency of delivery of adjuvant therapy. These results have significant implications for the planning of combination anticancer therapy. (Mol Cancer Res 2007;5(6):531–42)
HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma
Authors: Xu Jing , Xu Hui-Yun , Zhang Qing , Song Fei , Jiang Jian-Li , Yang Xiang-Min , Mi Li , Wen Ning , Tian Rong , Wang Li , Yao Hui , Feng Qiang , Zhang Yang , Xing Jin-Liang , Zhu Ping , Chen Zhi-Nan
Published: June 2007

CD147 molecule is reported to be correlated with the malignancy of some cancers; however, it remains unclear whether it is involved in the progression of hepatocellular carcinoma (HCC). Here, we investigated the function of HAb18G/CD147, a member of CD147 family, and its antibodies, HAb18 and LICARTIN, in HCC invasion and metastasis. We observed that HAb18G/CD147 gene silence in HCC cells significantly decreased the secretion of matrix metalloproteinase (MMP) and the invasive potential of HCC cells (P < 0.001). MMP silence in HCC cells also significantly suppressed the invasion of the cells when cocultured with fibroblasts; however, its inhibitory effect was significantly weaker than that of both HAb18G/CD147 silence in HCC cells and that of MMP silence in fibroblasts (P < 0.001). Blocking theHAb18G/CD147 molecule on HCC cells with HAb18 monoclonal antibody resulted in a similar suppressive effect on MMP secretion and cell invasion, but with no significant effects on the cell growth. 131I-labeled HAb18 F(ab′)2 (LICARTIN), however, significantly inhibited the in vitro growth of HCC cells (P < 0.001). In an orthotopic model of HCC in nude mice, HAb18 and LICARTIN treatment effectively reduced the tumor growth and metastasis as well as the expression of three major factors in the HCC microenviroment (MMPs, vascular endothelial growth factor, and fibroblast surface protein) in the paracancer tissues. Overall, these results suggest that HAb18G/CD147 plays an important role in HCC invasion and metastasis mainly via modulating fibroblasts, as well as HCC cells themselves to disrupt the HCC microenviroment. LICARTIN can be used as a drug targeting to HAb18G/CD147 in antimetastasis and recurrence therapy of HCC. (Mol Cancer Res 2007;5(6):605–14)
A Complex of EpCAM, Claudin-7, CD44 Variant Isoforms, and Tetraspanins Promotes Colorectal Cancer Progression
Authors: Kuhn Sebastian , Koch Moritz , Nübel Tobias , Ladwein Markus , Antolovic Dalibor , Klingbeil Pamela , Hildebrand Dagmar , Moldenhauer Gerhard , Langbein Lutz , Franke Werner W. , Weitz Jürgen , Zöller Margot
Published: June 2007

High expression of EpCAM and the tetraspanin CO-029 has been associated with colorectal cancer progression. However, opposing results have been reported on CD44 variant isoform v6 (CD44v6) expression. We recently noted in rat gastrointestinal tumors that EpCAM, claudin-7, CO-029, and CD44v6 were frequently coexpressed and could form a complex. This finding suggested the possibly that the complex, rather than the individual molecules, could support tumor progression. The expression of EpCAM, claudin-7, CO-029, and CD44v6 expression was evaluated in colorectal cancer (n = 104), liver metastasis (n = 66), and tumor-free colon and liver tissue. Coexpression and complex formation of the molecules was correlated with clinical variables and apoptosis resistance. EpCAM, claudin-7, CO-029, and CD44v6 expression was up-regulated in colon cancer and liver metastasis. Expression of the four molecules did not correlate with tumor staging and grading. However, coexpression inversely correlated with disease-free survival. Coexpression was accompanied by complex formation and recruitment into tetraspanin-enriched membrane microdomains (TEM). Claudin-7 contributes to complex formation inasmuch as in the absence of claudin-7, EpCAM hardly associates with CO-029 and CD44v6 and is not recruited into TEMs. Notably, colorectal cancer lines that expressed the EpCAM/claudin-7/CO-029/CD44v6 complex displayed a higher degree of apoptosis resistance than lines devoid of any one of the four molecules. Expression of EpCAM, claudin-7, CO-029, and CD44v6 by themselves cannot be considered as prognostic markers in colorectal cancer. However, claudin-7–associated EpCAM is recruited into TEM and forms a complex with CO-029 and CD44v6 that facilitates metastasis formation. (Mol Cancer Res 2007;5(6):553–67)
Metoprolol Reverses Left Ventricular Remodeling in Patients With Asymptomatic Systolic Dysfunction
Authors: Colucci Wilson S. , Kolias Theodore J. , Adams Kirkwood F. , Armstrong William F. , Ghali Jalal K. , Gottlieb Stephen S. , Greenberg Barry , Klibaner Michael I. , Kukin Marrick L. , Sugg Jennifer E.
Published: June 2007

Background—

There are no randomized, controlled trial data to support the benefit of β-blockers in patients with asymptomatic left ventricular systolic dysfunction. We investigated whether β-blocker therapy ameliorates left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Method and Results—

Patients with left ventricular ejection fraction <40%, mild left ventricular dilation, and no symptoms of heart failure (New York Heart Association class I) were randomly assigned to receive extended-release metoprolol succinate (Toprol-XL, AstraZeneca) 200 mg or 50 mg or placebo for 12 months. Echocardiographic assessments of left ventricular end-systolic volume, end-diastolic volume, mass, and ejection fraction were performed at baseline and at 6 and 12 months. The 149 patients randomized to the 3 treatment groups (200 mg, n=48; 50 mg, n=48; and placebo, n=53) were similar with regard to all baseline characteristics including age (mean, 66 years), gender (74% male), plasma brain natriuretic peptide (79 pg/mL), left ventricular end-diastolic volume index (110 mL/m
2
), and left ventricular ejection fraction (27%). At 12 months in the 200-mg group, there was a 14±3 mL/m
2
decrease (least square mean±SE) in end-systolic volume index and a 6±1% increase in left ventricular ejection fraction (
P
<0.05 versus baseline and placebo for both). The decrease in end-diastolic volume index (14±3) was different from that seen at baseline (
P
<0.05) but not with placebo. In the 50-mg group, end-systolic and end-diastolic volume indexes decreased relative to baseline but were not different from what was seen with placebo, whereas ejection fraction increased by 4±1% (
P
<0.05 versus baseline and placebo).

Conclusion—

β-Blocker therapy can ameliorate left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.
Treatment of Proximal Deep-Vein Thrombosis With the Oral Direct Factor Xa Inhibitor Rivaroxaban (BAY 59-7939)
Authors: Agnelli Giancarlo , Gallus Alexander , Goldhaber Samuel Z. , Haas Sylvia , Huisman Menno V. , Hull Russel D. , Kakkar Ajay K. , Misselwitz Frank , Schellong Sebastian
Published: June 2007

Background—

An effective and safe oral anticoagulant that needs no monitoring for dose adjustment is urgently needed for the treatment of diseases that require long-term anticoagulation. Rivaroxaban (BAY 59-7939) is an oral direct factor Xa inhibitor currently under clinical development.

Methods and Results—

This randomized, parallel-group phase II trial in patients with proximal deep-vein thrombosis explored the efficacy and safety of rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily compared with enoxaparin 1 mg/kg BID followed by vitamin K antagonist. Each treatment was administered for 12 weeks. The primary efficacy end point was an improvement in thrombotic burden at day 21 (assessed by quantitative compression ultrasonography; ≥4-point improvement in thrombus score) without recurrent symptomatic venous thromboembolism or venous thromboembolism-related death. The primary safety end point was major bleeding during 12 weeks of treatment. Outcomes were adjudicated centrally without knowledge of treatment allocation. The primary efficacy end point was achieved in 53 (53.0%) of 100, 58 (59.2%) of 98, 62 (56.9%) of 109, and 49 (43.8%) of 112 patients receiving rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily, respectively, compared with 50 (45.9%) of 109 patients treated with enoxaparin/vitamin K antagonist. There was no significant trend in the dose-response relationship between rivaroxaban BID and the primary efficacy end point (
P
=0.67). Major bleeding was observed in 1.7%, 1.7%, 3.3%, and 1.7% of patients receiving rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily, respectively. There were no major bleeding events with enoxaparin/vitamin K antagonist.

Conclusions—

Results of this proof-of-concept and dose-finding study support phase III evaluation of the orally active direct factor Xa inhibitor rivaroxaban, because efficacy and safety were apparent in the treatment of proximal deep-vein thrombosis across a 3-fold range of fixed daily dosing.
Abdominal Visceral and Subcutaneous Adipose Tissue Compartments
Authors: Fox Caroline S. , Massaro Joseph M. , Hoffmann Udo , Pou Karla M. , Maurovich-Horvat Pal , Liu Chun-Yu , Vasan Ramachandran S. , Murabito Joanne M. , Meigs James B. , Cupples L. Adrienne , D’Agostino Ralph B. , O’Donnell Christopher J.
Published: June 2007

Background—

Visceral adipose tissue (VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting.

Methods and Results—

Participants (n=3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005. Metabolic risk factors were examined in relation to increments of SAT and VAT after multivariable adjustment. Heritability was calculated using variance-components analysis. Among both women and men, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus, and metabolic syndrome (
P
range <0.01). In women, relations between VAT and risk factors were consistently stronger than in men. However, VAT was more strongly correlated with most metabolic risk factors than was SAT. For example, among women and men, both SAT and VAT were associated with increased odds of metabolic syndrome. In women, the odds ratio (OR) of metabolic syndrome per 1–standard deviation increase in VAT (OR, 4.7) was stronger than that for SAT (OR, 3.0;
P
for difference between SAT and VAT <0.0001); similar differences were noted for men (OR for VAT, 4.2; OR for SAT, 2.5). Furthermore, VAT but not SAT contributed significantly to risk factor variation after adjustment for body mass index and waist circumference (
P
≤0.01). Among overweight and obese individuals, the prevalence of hypertension, impaired fasting glucose, and metabolic syndrome increased linearly and significantly across increasing VAT quartiles. Heritability values for SAT and VAT were 57% and 36%, respectively.

Conclusions—

Although both SAT and VAT are correlated with metabolic risk factors, VAT remains more strongly associated with an adverse metabolic risk profile even after accounting for standard anthropometric indexes. Our findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot. Measurement of VAT may provide a more complete understanding of metabolic risk associated with variation in fat distribution.
Common
NOS1AP
Variants Are Associated With a Prolonged QTc Interval in the Rotterdam Study
Authors: Aarnoudse Albert-Jan L.H.J. , Newton-Cheh Christopher , de Bakker Paul I.W. , Straus Sabine M.J.M. , Kors Jan A. , Hofman Albert , Uitterlinden André G. , Witteman Jacqueline C.M. , Stricker Bruno H.C.
Published: June 2007

Background—

QT prolongation is an important risk factor for sudden cardiac death. About 35% of QT-interval variation is heritable. In a recent genome-wide association study, a common variant (rs10494366) in the nitric oxide synthase 1 adaptor protein (
NOS1AP
) gene was found to be associated with QT-interval variation. We tested for association of 2
NOS1AP
variants with QT duration and sudden cardiac death.

Methods and Results—

The Rotterdam Study is a population-based, prospective cohort study of individuals ≥55 years of age. The
NOS1AP
variants rs10494366 T>G and rs10918594 C>G were genotyped in 6571 individuals. Heart rate–corrected QT interval (QTc) was determined with ECG analysis software on up to 3 digital ECGs per individual (total, 11 108 ECGs from 5374 individuals). The association with QTc duration was estimated with repeated-measures analyses, and the association with sudden cardiac death was estimated by Cox proportional-hazards analyses. The rs10494366 G allele (36% frequency) was associated with a 3.8-ms (95% confidence interval, 3.0 to 4.6;
P
=7.8×10
−20
) increase in QTc interval duration for each additional allele copy, and the rs10918594 G allele (31% frequency) was associated with a 3.6-ms (95% confidence interval, 2.7 to 4.4;
P
=6.9×10
−17
) increase per additional allele copy. None of the inferred
NOS1AP
haplotypes showed a stronger effect than the individual single-nucleotide polymorphisms. There were 233 sudden cardiac deaths over 11.9 median years of follow-up. No significant association was observed with sudden cardiac death risk.

Conclusions—

Common variants in
NOS1AP
are strongly associated with QT-interval duration in an elderly population. Larger sample sizes are needed to confirm or exclude an effect on sudden cardiac death risk.
Coronary Artery Involvement in Children With Kawasaki Disease
Authors: McCrindle Brian W. , Li Jennifer S. , Minich L. LuAnn , Colan Steven D. , Atz Andrew M. , Takahashi Masato , Vetter Victoria L. , Gersony Welton M. , Mitchell Paul D. , Newburger Jane W.
Published: June 2007

Background—

Most studies of coronary artery involvement and associated risk factors in Kawasaki disease have used the Japanese Ministry of Health dichotomous criteria. Analysis of serial normalized artery measurements may reveal a broader continuous spectrum of involvement and different risk factors.

Methods and Results—

Clinical, laboratory, and echocardiographic measurements obtained at baseline and 1 week and 5 weeks after presentation were examined in 190 Kawasaki disease patients as part of a clinical trial of primary therapy with pulse steroids in addition to standard intravenous immunoglobulin. Maximum coronary artery
z
score normalized to body surface area was significantly greater than normal at all time points, decreasing significantly over time from baseline. A maximal
z
score ≥2.5 at any time was noted in 26% of patients. Japanese Ministry of Health dimensional criteria were met by 23% of patients. Significant independent factors associated with greater
z
score at any time included younger patient age, longer interval from disease onset to treatment with intravenous immunoglobulin, lower serum IgM level at baseline, and lower minimum serum albumin level.
z
Scores of the proximal right coronary artery were higher than those in the left anterior descending branch.

Conclusions—

Analyses of serial normalized coronary artery measurements in optimally treated Kawasaki disease patients demonstrated that for most patients, measurements are greatest at baseline and subsequently diminish; baseline measurements appear to be good predictors of involvement during early follow-up. When a more precise assessment is used, risk factors for coronary artery involvement are similar to those defined with arbitrary dichotomous criteria.
Is Isolated Nocturnal Hypertension a Novel Clinical Entity?
Authors: Li Yan , Staessen Jan A. , Lu Lu , Li Li-Hua , Wang Gu-Liang , Wang Ji-Guang
Published: June 2007

We reported previously that normotensive Chinese had higher nighttime diastolic blood pressure compared with non-Chinese. We, therefore, studied the prevalence and characteristics of isolated nocturnal hypertension (HT) and its association with arterial stiffness, an intermediate sign of target organ damage. We recorded ambulatory blood pressure, the central and peripheral systolic augmentation indexes, the ambulatory arterial stiffness index, and brachial-ankle pulse wave velocity in 677 Chinese enrolled in the JingNing population study (53.6% women; mean age: 47.6 years). Prevalence was 10.9% for isolated nocturnal HT (≥120/70 mm Hg from 10:00
pm
to 4:00
am
), 4.9% for isolated daytime HT (≥135/85 mm Hg from 8:00
am
to 6:00
pm
), and 38.4% for day-night HT. Patients with isolated nocturnal HT, compared with subjects with ambulatory normotension (45.8%), were older (53.7 versus 40.7 years), more often reported alcohol intake (68.9% versus 51.0%), had faster nighttime pulse rate (62.8 versus 60.7 bpm), had higher serum cholesterol (5.12 versus 4.77 mmol/L), and had higher blood glucose (4.84 versus 4.38 mmol/L). Similar to patients with isolated daytime HT or day-night HT, patients with isolated nocturnal HT had higher indexes of arterial stiffness (
P
<0.05) than subjects with ambulatory normotension (central augmentation index: 140% versus 134%; peripheral augmentation index: 82.6% versus 76.5%; ambulatory arterial stiffness index: 0.40 versus 0.35 U; brachial-ankle pulse wave velocity: 16.2 versus 14.7 m/s). Of 74 patients with isolated nocturnal HT, only 4 (5.4%) had hypertension on conventional office blood pressure measurement (≥140/90 mm Hg). In conclusion, isolated nocturnal HT can only be diagnosed by ambulatory blood pressure monitoring, is prevalent among Chinese, and is associated with increased arterial stiffness.
Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise
Authors: Van Guilder Gary P. , Westby Christian M. , Greiner Jared J. , Stauffer Brian L. , DeSouza Christopher A.
Published: June 2007

Increased endothelin-1–mediated vasoconstrictor tone has been linked to the etiology of a number of pathologies associated with human aging, including hypertension, congestive heart failure, and coronary artery disease. However, it is currently unclear whether aging, per se, is associated with enhanced endothelin-1 system activity. We hypothesized that endothelin-1 vasoconstrictor activity is greater in healthy older compared with young men and that regular aerobic exercise is an effective intervention for reducing endothelin-1 vasoconstrictor tone in older previously sedentary men. Forearm blood flow (plethysmography) responses to intra-arterial infusion of endothelin-1 (5 pmol/min; for 20 minutes) and selective (BQ-123; 100 nmol/min; for 60 minutes) and nonselective (BQ-123+BQ-788; 100 nmol/min; for 60 minutes) endothelin-1 receptor blockade were determined in 28 healthy, sedentary men: 13 younger (age: 27±1 years) and 15 older (age: 62±2 years). The vasoconstrictor response to endothelin-1 was significantly blunted (≈65%) in the older versus younger men. In response to BQ-123, resting forearm blood flow increased (≈20%;
P
<0.05) in the older but not in the younger men. The addition of BQ-788 to BQ-123 did not significantly affect the blood flow responses to BQ-123 in either group. Eight of the 15 older sedentary men completed a 3-month aerobic exercise intervention. After the intervention, the vasoconstrictor response to endothelin-1 was markedly increased (225%;
P
<0.05), whereas BQ-123 resulted in modest vasoconstriction in the previously sedentary older men. These results demonstrate that endothelin-1–mediated vasoconstrictor tone increases with age in healthy men but can be alleviated with regular aerobic exercise.
5-Hydroxytryptamine 1A/7 and 4α Receptors Differentially Prevent Opioid-Induced Inhibition of Brain Stem Cardiorespiratory Function
Authors: Wang Xin , Dergacheva Olga , Kamendi Harriet , Gorini Christopher , Mendelowitz David
Published: June 2007

Opioids evoke respiratory depression, bradycardia, and reduced respiratory sinus arrhythmia, whereas serotonin (5-HT) agonists stimulate respiration and cardiorespiratory interactions. This study tested whether serotonin agonists can prevent the inhibitory effects of opioids on cardiorespiratory function. Spontaneous and rhythmic inspiratory-related activity and γ-aminobutyric acid (GABA) neurotransmission to premotor parasympathetic cardioinhibitory neurons in the nucleus ambiguus were recorded simultaneously in an in vitro thick slice preparation. The μ-opioid agonist fentanyl inhibited respiratory frequency. The 5-hydroxytryptamine 1A/7 receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin increased respiratory frequency by itself and also prevented the fentanyl-induced respiratory depression. The 5-hydroxytryptamine 4α agonist BIMU-8 did not by itself change inspiratory activity but prevented the μ-opioid–mediated respiratory depression. Both spontaneous and inspiratory-evoked GABAergic neurotransmission to cardiac vagal neurons were inhibited by fentanyl. 8-Hydroxy-2-(di-n-propylamino)tetralin inhibited spontaneous but not inspiratory-evoked GABAergic activity to parasympathetic cardiac neurons. However, 8-hydroxy-2-(di-n-propylamino)tetralin differentially altered the opioid-mediated depression of inspiratory-evoked GABAergic activity but did not change the opioid-induced reduction in spontaneous GABAergic neurotransmission. In contrast, BIMU-8 did not alter GABAergic neurotransmission to cardiac vagal neurons by itself but prevented the fentanyl depression of both spontaneous and inspiratory-elicited GABAergic neurotransmission to cardiac vagal neurons. In the presence of tetrodotoxin, the inhibition of GABAergic inhibitory postsynaptic currents with fentanyl is prevented by coapplication of BIMU-8, indicating that BIMU-8 acts at presynaptic GABAergic terminals to prevent fentanyl-induced depression. These results suggest that activation of 5-hydroxytryptamine receptors, particularly 5-hydroxytryptamine 4α agonists, may be a useful therapeutic approach in preventing opioid-evoked cardiorespiratory depression.
North Pacific Decadal Variability in the Community Climate System Model Version 2
Authors: Kwon Young-Oh , Deser Clara
Published: June 2007

North Pacific decadal oceanic and atmospheric variability is examined from a 650-yr control integration of the Community Climate System Model version 2. The dominant pattern of winter sea surface temperature (SST) variability is similar to the observed “Pacific decadal oscillation,” with maximum amplitude along the Kuroshio Extension. SST anomalies in this region exhibit significant spectral peaks at approximately 16 and 40 yr. Lateral geostrophic heat flux divergence, caused by a meridional shift of the Kuroshio Extension forced by basin-scale wind stress curl anomalies 3–5 yr earlier, is responsible for the decadal SST variability; local surface heat flux and Ekman heat flux divergence act as a damping and positive feedback, respectively. A simple linear Rossby wave model is invoked to explicitly demonstrate the link between the wind stress curl forcing and decadal variability in the Kuroshio Extension. The Rossby wave model not only successfully reproduces the two decadal spectral peaks, but also illustrates that only the low-frequency (>10-yr period) portion of the approximately white noise wind stress curl forcing is relevant. This model also demonstrates that the weak and insignificant decadal spectral peaks in the wind stress curl forcing are necessary for producing the corresponding strong and significant oceanic peaks in the Kuroshio Extension. The wind stress curl response to decadal SST anomalies in the Kuroshio Extension is similar in structure but opposite in sign and somewhat weaker than the wind stress curl forcing pattern. These results suggest that the simulated North Pacific decadal variability owes its existence to two-way ocean–atmosphere coupling.
Resolving the Regional Signature of the Annular Modes
Authors: Kushner Paul J. , Lee Gabriel
Published: June 2007

A sector EOF analysis applied to the extratropical tropospheric circulation extracts robust circulation patterns that represent the regional signature of the annular modes. These regional patterns are eastward-propagating, long baroclinic wave structures with the dipolar meridional structure in the streamflow of the annular modes. The regional dipole patterns are also connected to the annular modes through their temporal correlation and their eddy flux signatures. These results serve to relate the hemispheric and the regional perspectives on the annular modes.
The Role of the Indonesian Throughflow in the Indo–Pacific Climate Variability in the GFDL Coupled Climate Model
Authors: Song Qian , Vecchi Gabriel A. , Rosati Anthony J.
Published: June 2007

The impacts of the Indonesian Throughflow (ITF) on the tropical Indo–Pacific climate, particularly on the character of interannual variability, are explored using a coupled general circulation model (CGCM). A pair of CGCM experiments—a control experiment with an open ITF and a perturbation experiment in which the ITF is artificially closed—is integrated for 200 model years, with the 1990 values of trace gases. The closure of the ITF results in changes to the mean oceanic and atmospheric conditions throughout the tropical Indo–Pacific domain as follows: surface temperatures in the eastern tropical Pacific (Indian) Ocean warm (cool), the near-equatorial Pacific (Indian) thermocline flattens (shoals), Indo–Pacific warm-pool precipitation shifts eastward, and there are relaxed trade winds over the tropical Pacific and anomalous surface easterlies over the equatorial Indian Ocean. The character of the oceanic changes is similar to that described by ocean-only model experiments, though the amplitude of many features in the tropical Indo–Pacific is amplified in the CGCM experiments.

In addition to the mean-state changes, the character of tropical Indo–Pacific interannual variability is substantially modified. Interannual variability in the equatorial Pacific and the eastern tropical Indian Ocean is substantially intensified by the closure of the ITF. In addition to becoming more energetic, El Niño–Southern Oscillation (ENSO) exhibits a shorter time scale of variability and becomes more skewed toward its warm phase (stronger and more frequent warm events). The structure of warm ENSO events changes; the anomalies of sea surface temperature (SST), precipitation, and surface westerly winds are shifted to the east and the meridional extent of surface westerly anomalies is larger.

In the eastern tropical Indian Ocean, the interannual SST variability off the coast of Java–Sumatra is noticeably amplified by the occurrence of much stronger cooling events. Closing the ITF shoals the eastern tropical Indian Ocean thermocline, which results in stronger cooling events through enhanced atmosphere–thermocline coupled feedbacks. Changes to the interannual variability caused by the ITF closure rectify into mean-state changes in tropical Indo–Pacific conditions. The modified Indo–Pacific interannual variability projects onto the mean-state differences between the ITF open and closed scenarios, rectifying into mean-state differences. These results suggest that CGCMs need to reasonably simulate the ITF in order to successfully represent not just the mean climate, but its variations as well.
Increasing Antarctic Sea Ice under Warming Atmospheric and Oceanic Conditions
Authors: Zhang Jinlun
Published: June 2007

Estimates of sea ice extent based on satellite observations show an increasing Antarctic sea ice cover from 1979 to 2004 even though in situ observations show a prevailing warming trend in both the atmosphere and the ocean. This riddle is explored here using a global multicategory thickness and enthalpy distribution sea ice model coupled to an ocean model. Forced by the NCEP–NCAR reanalysis data, the model simulates an increase of 0.20 × 1012 m3 yr−1 (1.0% yr−1) in total Antarctic sea ice volume and 0.084 × 1012 m2 yr−1 (0.6% yr−1) in sea ice extent from 1979 to 2004 when the satellite observations show an increase of 0.027 × 1012 m2 yr−1 (0.2% yr−1) in sea ice extent during the same period. The model shows that an increase in surface air temperature and downward longwave radiation results in an increase in the upper-ocean temperature and a decrease in sea ice growth, leading to a decrease in salt rejection from ice, in the upper-ocean salinity, and in the upper-ocean density. The reduced salt rejection and upper-ocean density and the enhanced thermohaline stratification tend to suppress convective overturning, leading to a decrease in the upward ocean heat transport and the ocean heat flux available to melt sea ice. The ice melting from ocean heat flux decreases faster than the ice growth does in the weakly stratified Southern Ocean, leading to an increase in the net ice production and hence an increase in ice mass. This mechanism is the main reason why the Antarctic sea ice has increased in spite of warming conditions both above and below during the period 1979–2004 and the extended period 1948–2004.
Quantifying the Dependence of Westerly Wind Bursts on the Large-Scale Tropical Pacific SST
Authors: Tziperman Eli , Yu Lisan
Published: June 2007

The correlation between parameters characterizing observed westerly wind bursts (WWBs) in the equatorial Pacific and the large-scale SST is analyzed using singular value decomposition. The WWB parameters include the amplitude, location, scale, and probability of occurrence for a given SST distribution rather than the wind stress itself. This approach therefore allows for a nonlinear relationship between the SST and the wind signal of the WWBs. It is found that about half of the variance of the WWB parameters is explained by only two large-scale SST modes. The first mode represents a developed El Niño event, while the second mode represents the seasonal cycle. More specifically, the central longitude of WWBs, their longitudinal extent, and their probability seem to be determined to a significant degree by the ENSO-driven signal. The amplitude of the WWBs is found to be strongly influenced by the phase of the seasonal cycle. It is concluded that the WWBs, while partially stochastic, seem an inherent part of the large-scale deterministic ENSO dynamics. Implications for ENSO predictability and prediction are discussed.
Interannual to Decadal Predictability of Tropical and North Pacific Sea Surface Temperatures
Authors: Newman Matthew
Published: June 2007

A multivariate empirical model is used to show that predictability of the dominant patterns of tropical and North Pacific oceanic variability, El Niño–Southern Oscillation (ENSO), and the Pacific decadal oscillation (PDO), is mostly limited to little more than a year, despite the presence of spectral peaks on decadal time scales. The model used is a linear inverse model (LIM) derived from the observed simultaneous and 1-yr lag correlation statistics of July–June-averaged SST from the Hadley Centre Global Sea Ice and Sea Surface Temperature (HadISST) dataset for the years 1900–2002. The model accurately reproduces the power spectra of the data, including interannual and interdecadal spectral peaks that are significant relative to univariate red noise. Eigenanalysis of the linear dynamical operator yields propagating eigenmodes that correspond to these peaks but have very short decay times and, thus, limited predictability.

Longer-term predictability does exist, however, due to two stationary eigenmodes that are more weakly damped. These eigenmodes do not strongly correspond to the canonical ENSO and PDO patterns. Instead, one is similar to the 1900–2002 trend and might represent anthropogenic effects, while the second represents multidecadal fluctuations of a pattern that potentially represents natural decadal variability; however, neither attribution can be made unambiguously with the analysis presented in this paper. Predictability of these two stationary eigenmodes is significantly enhanced by tropical–North Pacific coupling. Neither stationary eigenmode is well captured in the control run of any coupled GCM in the CMIP-3 project of the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4), perhaps because in all of the GCMs tropical SST decadal variability is too weak and North Pacific SSTs are too independent of the Tropics.

A key implication of this analysis is that the PDO may represent not a single physical mode but rather the sum of several phenomena, each of which represents a different red noise with its own autocorrelation time scale and spatial pattern. The sum of these red noises can give rise to apparent PDO “regime shifts” and seeming characteristics of a long memory process. Such shifts are not predictable beyond the time scale of the most rapidly decorrelating noise, less than two years, although the expected duration of regimes may be determined from the relative amplitudes of different eigenmodes.
What Maintains the SST Front North of the Eastern Pacific Equatorial Cold Tongue?*
Authors: de Szoeke Simon P. , Xie Shang-Ping , Miyama Toru , Richards Kelvin J. , Small R. Justin O.
Published: June 2007

A coupled ocean–atmosphere regional model suggests a mechanism for formation of a sharp sea surface temperature (SST) front north of the equator in the eastern Pacific Ocean in boreal summer and fall. Meridional convergence of Ekman transport at 5°N is forced by eastward turning of the southeasterly cross-equatorial wind, but the SST front forms considerably south of the maximum Ekman convergence. Geostrophic equatorward flow at 3°N in the lower half of the isothermally mixed layer enhances mixed layer convergence.

Cold water is upwelled on or south of the equator and is advected poleward by mean mixed layer flow and by eddies. The mixed layer current convergence in the north confines the cold advection, so the SST front stays close to the equator. Warm advection from the north and cold advection from the south strengthen the front. In the Southern Hemisphere, a continuous southwestward current advects cold water far from the upwelling core.

The cold tongue is warmed by the net surface flux, which is dominated by solar radiation. Evaporation and net surface cooling are at a maximum just north of the SST front where relatively cool dry air is advected northward over warm SST. The surface heat flux is decomposed into a response to SST alone, and an atmospheric feedback. The atmospheric feedback enhances cooling on the north side of the front by 178 W m−2, about half of which is due to enhanced evaporation from cold dry advection, while the other half is due to cloud radiative forcing.
Origins of Dry Air in the Tropics and Subtropics
Authors: Cau Piero , Methven John , Hoskins Brian
Published: June 2007

The humidity in the dry regions of the tropical and subtropical troposphere has a major impact on the ability of the atmosphere to radiate heat to space. The water vapor content in these regions is determined by their “origins,” here defined as the last condensation event following air masses. Trajectory simulations are used to investigate such origins using the 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40) data for January 1993. It is shown that 96% of air parcels experience condensation within 24 days and most of the remaining 4% originate in the stratosphere. Dry air masses are shown to experience a net pressure increase since last condensation, which is uniform with latitude, while the median time taken for descent is 5 days into the subtropics but exceeds 16 days into the equatorial lower troposphere. The associated rate of decrease in potential temperature is consistent with radiative cooling. The relationship between the drier regions in the Tropics and subtropics and the geographical localization of their origin is investigated. Four transport processes are identified to explain these relationships.
Evidence for a Rapid Global Climate Shift across the Late 1960s
Authors: Baines Peter G. , Folland Chris K.
Published: June 2007

It is shown that a number of important characteristics of the global atmospheric circulation and climate changed in a near-monotonic fashion over the decade, or less, centered on the late 1960s. These changes were largest or commonest in tropical regions, the Southern Hemisphere, and the Atlantic sector of the Northern Hemisphere. Some, such as the decrease in rainfall in the African Sahel, are well known. Others appear to be new, but their combined extent is global and dynamical linkages between them are evident. The list of affected variables includes patterns of SST; tropical rainfall in the African Sahel and Sudan, the Amazon basin, and northeast Brazil; pressure and SST in the tropical North Atlantic and the west and central Pacific; various branches of the southern Hadley circulation and the southern subtropical jet stream; the summer North Atlantic Oscillation; south Greenland temperature; the Southern Hemisphere storm track; and, quite likely, the Antarctic sea ice boundary. These changes are often strongest in the June–August season; changes are also seen in December–February but are generally smaller. In Greenland, annual mean temperature seems to be affected strongly, reflecting similar changes in SST throughout the year in the higher latitudes of the North Atlantic. Possible causes for these coordinated changes are briefly evaluated. The most likely candidates appear to be a likely reduction in the northward oceanic heat flux associated with the North Atlantic thermohaline circulation in the 1950s to 1970s, which was nearly in phase with a rapid increase in anthropogenic aerosol emissions during the 1950s and 1960s, particularly over Europe and North America.
A Bayesian Assessment of Climate Change Using Multimodel Ensembles. Part II: Regional and Seasonal Mean Surface Temperatures
Authors: Min Seung-Ki , Hense Andreas
Published: June 2007

A Bayesian approach is applied to the observed regional and seasonal surface air temperature (SAT) changes using single-model ensembles (SMEs) with the ECHO-G model and multimodel ensembles (MMEs) of the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) simulations. Bayesian decision classifies observations into the most probable scenario out of six available scenarios: control (CTL), natural forcing (N), anthropogenic forcing (ANTHRO), greenhouse gas (G), sulfate aerosols (S), and natural plus anthropogenic forcing (ALL). Space–time vectors of the detection variable are constructed for six continental regions (North America, South America, Asia, Africa, Australia, and Europe) by combining temporal components of SATs (expressed as Legendre coefficients) from two or three subregions of each continental region.

Bayesian decision results show that over most of the regions observed SATs are classified into ALL or ANTHRO scenarios for the whole twentieth century and its second half. Natural forcing and ALL scenarios are decided during the first half of the twentieth century, but only in the low-latitude region (Africa and South America), which might be related to response patterns to solar forcing. Overall seasonal decisions follow annual results, but there are notable seasonal dependences that differ between regions. A comparison of SME and MME results demonstrates that the Bayesian decisions for regional-scale SATs are largely robust to intermodel uncertainties as well as prior probability and temporal scales, as found in the global results.
Intraseasonal Convective Perturbations Related to the Seasonal March of the Indo-Pacific Monsoons
Authors: Bellenger H. , Duvel J. P.
Published: June 2007

The seasonal evolution of the 20–90-day intraseasonal variability (ISV) of the convection in the Indo-Pacific region presents intriguing features related to monsoon dynamics: (i) a sharp ISV maximum in May for the southern Bay of Bengal and in June for the eastern Arabian Sea, (ii) a maximum ISV over the west Pacific in July–September when the ISV over the northern Indian Ocean is weaker, (iii) a persistent ISV north of Australia from December to March, and (iv) a weak ISV over continental regions. The source of these behaviors is investigated from time series of satellite observations, meteorological reanalysis, and from an ocean mixed layer depth (MLD) climatology. For the northern Indian Ocean, sharp ISV maxima in May and June, when the MLD is still small (∼20–30 m), are related to an abrupt surface cooling associated with the setting of the monsoon low-level jet. The ISV of the convection is smaller over these regions during July–September when the MLD is deepened (∼60–70 m) by the monsoon low-level wind forcing. At this time, the low-level wind is weak over the west Pacific, the MLD is small, and the amplitude of the ISV remains large. North of Australia, and also over the south equatorial Indian Ocean, there is no particular reinforcement of the ISV near the onset. A weak low-level jet and a small MLD prevail during the whole monsoon season in good agreement with a more uniform ISV. These results support the hypothesis that a moderately shallow (∼20–30 m) ocean mixed layer is important for maintaining locally the ISV of the convection, when the conditions (e.g., SST, large-scale circulation) for such an ISV to exist are satisfied. The seasonal variability of the MLD, related in part to the monsoon low-level jet variability over the tropical oceans, thus gives a link between the seasonal march of monsoon circulations and the seasonal evolution of the ISV of the convection. This has implications for a better understanding of the origin of the ISV and for the predictability of its amplitude, especially near the monsoon onset date.
Diagnosing Summertime Mesoscale Vertical Motion: Implications for Atmospheric Data Assimilation
Authors: Pagé Christian , Fillion Luc , Zwack Peter
Published: June 2007

Balance omega equations have recently been used to try to improve the characterization of balance in variational data assimilation schemes for numerical weather prediction (NWP). Results from Fisher and Fillion et al. indicate that a quasigeostrophic omega equation can be used adequately in the definition of the control variable to represent synoptic-scale balanced vertical motion. For high-resolution limited-area data assimilation and forecasting (1–10-km horizontal resolution), such a diagnostic equation for vertical motion needs to be revisited. Using a state-of-the-art NWP forecast model at 2.5-km horizontal resolution, these issues are examined. Starting from a complete diagnostic partial differential equation for omega, the rhs forcing terms were computed from model-generated fields. These include the streamfunction, temperature, and physical time tendencies of temperature in gridpoint space. To accurately compute one term of second-order importance (i.e., the ageostrophic vorticity tendency forcing term), a special procedure was used. With this procedure it is shown that Charney’s balance equation brings significant information in order to deduce the geostrophic time tendency term. Under these conditions, results show that for phenomena of length scales of 15–100 km over convective regions, a diagnostic equation can capture the major part of the model-generated vertical motion. The limitations of the digital filter initialization approach when used as in Fillion et al. with a cutoff period reduced to 1 h are also illustrated. The potential usefulness of this study for mesoscale atmospheric data assimilation is briefly discussed.