bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation by the steroid/thyroid hormone superfamily of TGF‐β‐stimulated VEGF release from vascular smooth muscle cells
Authors: Tanabe Kumiko , Tokuda Haruhiko , Takai Shinji , Matsushima‐Nishiwaki Rie , Hanai Yoshiteru , Hirade Kouseki , Katagiri Yoshihiro , Dohi Shuji , Kozawa Osamu
Published: April 2006

We previously reported that transforming growth factor‐β (TGF‐β) stimulates the release of vascular endothelial growth factor (VEGF) from aortic smooth muscle A10 cells via activation of p38 mitogen‐activated protein (MAP) kinase. In the present study, we investigated whether nuclear hormone receptor superfamily members affect TGF‐β‐stimulated VEGF release from A10 cells. Retinoic acid or 1,25‐dihydroxyvitamin D3 enhanced TGF‐β‐induced VEGF release in a concentration‐dependent manner, whereas dexamethasone or corticosterone suppressed TGF‐β‐induced VEGF release. 1,25‐Dihydroxyvitamin D3 and TGF‐β stimulated phosphorylation of p38 MAP kinase in an additive manner. SB203580, an inhibitor of p38 MAP kinase, decreased the VEGF release induced by TGF‐β or 1,25‐dihydroxyvitamin D3. However, retinoic acid, dexamethasone, or corticosterone did not affect phosphorylation of p38 MAP kinase. These results indicate that retinoic acid, 1,25‐dihydroxyvitamin D3, and glucocorticoids affect TGF‐β‐stimulated VEGF release from aortic smooth muscle cells. The stimulatory effect of 1,25‐dihydroxyvitamin D3 occurs, in part, via modification of TGF‐β‐induced activation of p38 MAP kinase. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
CREB‐dependent cyclooxygenase‐2 and microsomal prostaglandin E synthase‐1 expression is mediated by protein kinase C and calcium
Authors: Pham Hung , Shafer Lindsay M. , Slice Lee W.
Published: April 2006

Cellular production of prostaglandins (PGs) is controlled by the concerted actions of cyclooxygenases (COX) and terminal PG synthases on arachidonic acid in response to agonist stimulation. Recently, we showed in an ileal epithelial cell line (IEC‐18), angiotensin II‐induced COX‐2‐dependent PGI2 production through p38MAPK, and calcium mobilization (J. Biol. Chem. 280: 1582–1593, 2005). Agonist binding to the AT1 receptor results in activation of PKC activity and Ca2+ signaling but it is unclear how each pathway contributes to PG production. IEC‐18 cells were stimulated with either phorbol‐12,13‐dibutyrate (PDB), thapsigargin (TG), or in combination. The PG production and COX‐2 and PG synthase expression were measured. Surprisingly, PDB and TG produced PGE2 but not PGI2. This corresponded to induction of COX‐2 and mPGES‐1 mRNA and protein. PGIS mRNA and protein levels did not change. Activation of PKC by PDB resulted in the activation of ERK1/2, JNK, and CREB whereas activation of Ca2+ signaling by TG resulted in the delayed activation of ERK1/2. The combined effect of PKC and Ca2+ signaling were prolonged COX‐2 and mPGES‐1 mRNA and protein expression. Inhibition of PKC activity, MEK activity, or Ca2+ signaling blocked agonist induction of COX‐2 and mPGES‐1. Expression of a dominant negative CREB (S133A) blocked PDB/TG‐dependent induction of both COX‐2 and mPGES‐1 promoters. Decreased CREB expression by siRNA blocked PDB/TG‐dependent expression of COX‐2 and mPGES‐1 mRNA. These findings demonstrate a coordinated induction of COX‐2 and mPGES‐1 by PDB/TG that proceeds through PKC/ERK and Ca2+ signaling cascades, resulting in increased PGE2 production. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Nuclease sensitive element binding protein 1 gene disruption results in early embryonic lethality
Authors: Fan Lin , Jones Stephen N. , Padden Carolyn , Shen Qichang , Newburger Peter E.
Published: April 2006

Nuclease sensitive element binding protein 1 (NSEP1) is a member of the EFIA/NSEP1/YB‐1 family of DNA‐binding proteins whose members share a cold shock domain; it has also been termed DNA‐binding protein B and Y box binding protein‐1 because of its recognition of transcriptional regulatory elements. In addition, NSEP1 functions in the translational regulation of renin, ferritin, and interleukin 2 transcripts, and our laboratory has reported that it plays a role in the biosynthesis of selenium‐containing proteins. To test the functional importance of NSEP1 in murine embryonic development, we have utilized a clone of ES cells in which the NSEP1 gene had been disrupted by integration of a plasmid gene‐trapping vector into the seventh exon. Injection of these cells into C57BL/6 blastocysts resulted in 11 high percentage chimeric mice; crosses to wild type C57BL/6 mice generated 82 F1 agouti mice, indicating germ line transmission of the ES cell clone, but genotyping showed no evidence of the disrupted allele in any of these agouti offspring even though spermatozoa from four of five tested mice contained the targeted allele. Embryos harvested after timed matings of chimeric male mice demonstrated only the wildtype allele in 27 embryos tested at E7.5, E12.5, and E18.5. These results suggest that gene targeting of NSEP1 induces a lethal phenotype in early embryos, due to either haploinsufficiency of NSEP1 or formation of a dominant negative form of the protein. In either case, these data indicate the functional importance of the NSEP1 gene in murine early embryonic development. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Diabetes modulates differentially creatine kinase‐specific activity responsiveness to estradiol‐17β and to raloxifene in rat organs
Authors: Somjen Dalia , Shen Michal , Stern Naftali , Mirsky Nitsa
Published: April 2006

Diabetes mellitus increases the risk for CVD in women. While there is considerable evidence suggesting beneficial effects of estrogen on decreasing lipid peroxidation, atherosclerotic processes, and cardiovascular diseases, diabetes negates most estrogen protective effects as well as the skeletal protective effects of estrogens, which are not discernable in diabetic women. In the present study, we examined the in vivo effects of estradiol‐17β (E2), on creatine kinase (CK)‐specific activity, in estrogen‐responsive organs from healthy and diabetic rats. Healthy or diabetic (streptozotocin‐induced) female rats were injected with either E2 (10–50 µg/rat) or raloxifene (Ral; 500–1,000 µg/rat). Twenty‐four hours following the injection, animals were sacrificed; their organs removed and assayed for CK‐specific activity. CK‐specific activity in different organs [Left ventricle of heart (Lv), uterus (Ut), aorta (Ao), para uterine adipose tissue (Ad), epiphyseal cartilage (Ep), and diaphyseal bone (Di)] from healthy animals, was stimulated with increased doses of E2, with maximum at 20 µg/rat. Age‐matched diabetic female rats exhibited a remarkable decreased response to E2 in all organs except Ut. In contrast, the response to Ral was not altered in diabetic rats. Similar results were observed in organs from ovariectomized female rats (Ovx), healthy or diabetic. These results support our previous in vitro findings, demonstrating that hyperglycemia decreases CK response to E2 but not to Ral in cultured human vascular and bone cells. In summary, diabetes mellitus decreases CK response to E2 but not that of Ral in skeletal and vascular tissues. The decreased response to E2 detected in organs derived from diabetic rats might be due to changes in nuclear and/or membrane estrogen receptors and/or other genomic and non‐genomic pathways, as was shown in in vitro cellular models. J. Cell. Biochem. 99: 133–139, 2006. © 2006 Wiley‐Liss, Inc.
Downregulation of the RECK‐tumor and metastasis suppressor gene in glioma invasiveness
Authors: Corrẽa Tatiana C. Silveira , Brohem Carla Abdo , Winnischofer Sheila Maria Brochado , da Silva Cardeal Laura Beatriz , Sasahara Regina Maki , Taboga Sebastião Roberto , Sogayar Mari Cleide , Maria‐Engler Silvya Stuchi
Published: April 2006

Invasive behavior is the pathological hallmark of malignant gliomas, being responsible for the failure of surgery, radiation, and chemotherapy. Matrix metalloproteinases (MMPs) are essential for proper ECM remodeling and invasion. The tumor and metastasis suppressor RECK protein regulates at least three members of the MMPs family: MMP‐2, MMP‐9, and MT1‐MMP. In order to mimic the in vivo invasion process, A172 and T98G, respectively, non‐invasive and invasive human glioblastoma cell lines, were cultured onto uncoated (control) or type I collagen gel‐coated surface, and maintained for up to 7 days to allow establishment of the invasive process. We show that the collagen substrate causes decreased growth rates and morphological alterations correlated with the invasive phenotype. Electronic transmission microscopy of T98G cells revealed membrane invaginations resembling podosomes, which are typically found in cells in the process of crossing tissue boundaries, since they constitute sites of ECM degradation. Real time PCR revealed higher RECK mRNA expression in A172 cells, when compared to T98G cells and, also, in samples obtained from cultures where the invasive process was fully established. Interestingly, the collagen substrate increases RECK expression in A172 cells and the same tendency is displayed by T98G cells. MMPs‐2 and ‐9 displayed higher levels of expression and activity in T98G cells, and their activities are also upregulated by collagen. Therefore, we suggest that: (1) RECK downregulation is critical for the invasiveness process displayed by T98G cells; (2) type 1 collagen could be employed to modulate RECK expression in glioblastoma cell lines. Since a positive correlation between RECK expression and patients survival has been noted in several types of tumors, our results may contribute to elucidate the complex mechanisms of malignant gliomas invasiveness. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Inhibition of PP2A, but not PP5, mediates p53 activation by low levels of okadaic acid in rat liver epithelial cells
Authors: Messner Donald J. , Romeo Charles , Boynton Alton , Rossie Sandra
Published: April 2006

The microbial toxin okadaic acid (OA) specifically inhibits PPP‐type ser/thr protein phosphatases. OA is an established tumor promoter with numerous cellular effects that include p53‐mediated cell cycle arrest. In T51B rat liver epithelial cells, a model useful for tumor promotion studies, p53 activation is induced by tumor‐promoting (low nanomolar) concentrations of OA. Two phosphatases sensitive to these concentrations of OA, PP2A and protein phosphatase 5 (PP5), have been implicated as negative regulators of p53. In this study we examined the respective roles of these phosphatases in p53 activation in non‐neoplastic T51B cells. Increases in p53 activity were deduced from levels of p21 (cip1) and/or the rat orthologue of mdm2, two p53‐regulated gene products whose induction was blocked by siRNA‐mediated knockdown of p53. As observed with 10 nM OA, both phospho‐ser15‐p53 levels and p53 activity were increased by 10 µM fostriecin or SV40 small t‐antigen. Both of these treatments selectively inhibit PP2A but not PP5. siRNA‐mediated knockdown of PP2A, but not PP5, also increased p53 activity. Finally, adenoviral‐mediated over‐expression of an OA‐resistant form of PP5 did not prevent increased phospho‐ser15‐p53, p53 protein, or p53 activity caused by 10 nM OA. Together these results indicate that PP5 blockade is not responsible for OA‐induced p53 activation and G1 arrest in T51B cells. In contrast, specific blockade of PP2A mimics p53‐related responses to OA in T51B cells, suggesting that PP2A is the target for this response to OA. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Differential expression of proteins in kidney, eye, aorta, and serum of diabetic and non‐diabetic rats
Authors: Cho William C. , Yip Tai‐Tung , Chung Wai‐Shing , Leung Albert W. , Cheng Christopher H. , Yue Kevin K.
Published: April 2006

Diabetes mellitus (DM) is a chronic progressive disease that often results in microvascular and macrovascular complications, yet its pathogenesis is not clear. Automated proteomic technology, coupled with powerful bioinformatics and statistical tools, can provide new insights into the molecular alterations implicated in DM. Following our previous findings of redox changes in the eye and aorta of diabetic rats, as well as the activities of different antioxidant enzymes during the development of DM, this study is further launched to find potential biomarkers by comparing the serum and tissue samples of 26 diabetic rats (8 weeks after streptozotocin [STZ] administration) with 29 normal controls using surface enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF MS) technology. Eight potential biomarkers were found in the serum, one potential biomarker was found in the kidney and eye, respectively, whereas three potential biomarkers were discovered in the aorta. One of the serum biomarker candidates was found to match the C‐reactive protein (CRP) in the Swiss‐Prot knowledgebase. Further validation has been conducted by ELISA kit to confirm the role of CRP during the development of DM. To conclude, the increased level of CRP in diabetic serum demonstrated in this study indicates that the development of DM is associated with inflammation. This is also the first report demonstrating that some potential lysate biomarkers in the kidney, eye, and aorta may be involved in the development of diabetes and its complications. Further identification and evaluation of these potential biomarkers will help unravel the underlying mechanisms of the disease. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Post‐translational modification by O‐GlcNAc: Another way to change protein function
Authors: Kudlow Jeffrey E.
Published: April 2006

Modification of intracellular proteins by the β‐linkage of the monosaccharide, N‐acetylglucosamine to serine or threonine hydroxyls (O‐GlcNAc) is abundant and reversible. Although many proteins bear this post‐translational covalent modification, the changes in function of the proteins as a result of this modification are only starting to be understood. In this article, we describe how aspects of the flux from the glucose backbone to this modification are modified and how the cellular activity and content of the GC‐box binding transcription factor, Sp1, is altered by O‐glycosylation. The association of the enzyme that puts on the O‐GlcNAc modification with the bi‐functional enzyme that removes this modification is discussed relative to the transition between transcriptional repression and activation. J. Cell. Biochem. 98: 1062–1075, 2006. © 2006 Wiley‐Liss, Inc.
Pro‐metastasis function of TGFβ mediated by the smad pathway
Authors: Kang Yibin
Published: April 2006

The transforming growth factor beta (TGFβ) signaling pathway plays a vital role in the development and homeostasis of normal tissues. Abnormal function of this pathway contributes to the initiation and progression of cancer. Smad proteins are key signal transducers of the TGFβ pathway and are essential for the growth suppression function of TGFβ. Smads are bona fide tumor suppressors whose mutation, deletion, and silencing are associated with many types of human cancer. However, the involvement and functional mechanism of Smad proteins in cancer metastasis are poorly defined. Recent studies using genetically modified cancer cells and mouse tumor models have provided concrete evidence for a Smad‐dependent mechanism for metastasis promotion by TGFβ. Understanding the dual roles of Smad proteins in tumor initiation and progression has important implications for cancer therapeutics. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Gene therapy for HIV infection: what does it need to make it work?
Authors: von Laer Dorothee , Hasselmann Susanne , Hasselmann Klaus
Published: April 2006

The efficacy of antiviral drug therapy for HIV infection is limited by toxicity and viral resistance. Thus, alternative therapies need to be explored. Several gene therapeutic strategies for HIV infection have been developed, but in clinical testing therapeutically effective levels of the transgene product were not achieved. This review focuses on the determinants of therapeutic efficacy and discusses the potential and also the limits of current gene therapy approaches for HIV infection. Copyright © 2006 John Wiley & Sons, Ltd.
Routine rapid HIV testing in hospitals: Another opportunity for hospitalists to improve care
Authors: Greenwald Jeffrey L.
Published: April 2006

BACKGROUND

The Centers for Disease Control and Prevention recommends routinely offering HIV testing to inpatients at hospitals with an HIV seroprevalence rate of greater than 1% or an AIDS diagnosis rate of greater than 1.0 per 1000 discharges. This recommendation has not been widely adopted, perhaps because of one of several barriers: the cost of implementing a counseling and testing program; the logistics of HIV counseling and testing on a hospital ward particularly with respect to privacy; concern about the follow‐up of HIV test results necessitating patients to return after discharge; and the cultural mindset of screening as an outpatient modality complicated by the fear of raising the possibility of HIV testing and therefore eliciting a negative reaction from a patient who has not requested it.

PURPOSE

This article focuses on these barriers and some possible solutions, emphasizing the role of FDA‐approved rapid HIV tests, which may decrease follow‐up issues for HIV testing programs. It also considers hospitalists, given their frontline status and ability to coordinate the multidisciplinary services and systemwide approach required to implement such a program, as leaders in this area. Journal of Hospital Medicine 2006;1:106–112. © 2006 Society of Hospital Medicine
Acute aortic dissection
Authors: Siegal Eric M.
Published: April 2006

Acute aortic dissection is an uncommon but lethal cause of acute chest, back, and abdominal pain. Establishing a timely diagnosis is paramount, as mortality from acute aortic dissection rises by the hour. Physical findings are protean and may include acute aortic valve insufficiency, peripheral pulse deficits, a variety of neurologic deficits, or end‐organ ischemia. The keys to establishing a timely diagnosis are maintaining a high index of suspicion and quickly obtaining a diagnostic study. CT angiography, magnetic resonance imaging, transesophageal echocardiography, and, to a lesser extent, aortography are all highly accurate imaging modalities. The choice of study should be driven by the clinical stability of the patient, the information required and the resources available at presentation. Proximal dissections are surgical emergencies, but distal dissections are generally treated medically. Endovascular stents are gaining favor for use in the repair of both acute and chronic distal dissections. Long‐term outcome data for endovascular stenting are still limited, and it remains unclear when stenting should be favored over surgery or medical therapy. Journal of Hospital Medicine 2006;1:94–105. © 2006 Society of Hospital Medicine
Curriculum development: The venous thromboembolism quality improvement resource room
Authors: McKean Sylvia , Stein Jason , Maynard Greg , Budnitz Tina , Amin Alpesh , Johnson Scott , Wellikson Larry
Published: April 2006

BACKGROUND

The role of the hospitalist has evolved over the last decade, with hospitalists increasingly being asked to lead systems‐based initiatives to improve the quality of inpatient care. The educational strategy of the Society of Hospital Medicine (SHM) includes development of practice‐based resources to support hospitalist‐led improvement in clinically important measures of hospital care quality.

OBJECTIVE

To develop a resource at the SHM Web site to present quality improvement (QI) principles for systems‐based care in the hospital and to help individual hospitalists improve specific patient outcomes.

DESIGN

The SHM defined the role of the hospitalist in QI, performed an assessment of the educational needs of hospitalists, and executed a Web‐based educational strategy to address these needs. The organization identified the most common cause of preventable inpatient deaths, hospital‐acquired venous thromboembolism (VTE), and prioritized the need to improve prophylaxis.

RESULTS

This new resource at the SHM Web site presents principles for conducting QI in the hospital. To enable learning that is practice based, the VTE Quality Improvement Resource Room (QI RR) features Ask the Expert, an interactive discussion community, and an original Improvement Workbook, a downloadable project outline and tutorial that hospitalists can use to guide and document steps in an effort aimed at reducing hospital‐acquired VTE.

CONCLUSIONS

This QI resource serves as a template for the development of subsequent hospital‐based resources. User feedback will refine the QI RR and its format so that similar offerings can target other significant inpatient problems. Additional research is needed to evaluate learning and the clinical impact of this quality improvement resource on hospital performance measures and patient outcomes. Journal of Hospital Medicine 2006;1:124–132. © 2006 Society of Hospital Medicine.
How hospitalists spend their time: Insights on efficiency and safety
Authors: O'Leary Kevin J. , Liebovitz David M. , Baker David W.
Published: April 2006

BACKGROUND

Despite the dramatic growth of hospitalists, no studies have evaluated the type and frequency of activities that hospitalists perform. To evaluate the types and frequency of activities that hospitalists perform during routine work, we conducted a time‐motion study of hospitalist physicians at our institution.

DESIGN

A research assistant shadowed hospitalist physicians for 3‐ to 5‐hour periods. Observation periods were distributed in order to sample all parts of a typical day of a hospitalist, including both admitting and nonadmitting periods. Activities were recorded on a standardized data collection form in 1‐minute intervals. Incoming pages were recorded as well.

RESULTS

Ten hospitalists were shadowed by a single research assistant for a total of 4467 minutes. Hospitalists spent 18% of their time on direct patient care, 69% on indirect patient care, 4% on personal activities, and 3% each on professional development, education, and travel. Communication accounted for 24% of the total minutes. Multitasking, performing more than one activity at the same time, was done 21% of the time. Hospitalists received an average of 3.4 ± 1.5 pages per hour.

CONCLUSIONS

Hospitalists spent most of their time on indirect patient care activities and relatively little time on direct patient care. Hospitalists spent a large amount of time on communication, underscoring the need for hospitalists to have outstanding communication skills and systems that support efficient communication. Multitasking and paging interruptions were common. The inherent distraction caused by interruptions and multitasking is a potential contributor to medical error and warrants further study. Journal of Hospital Medicine 2006;1:88–93. © 2006 Society of Hospital Medicine.
The history of sweet taste: not exactly a piece of cake
Authors: Temussi Pierandrea
Published: April 2006

Understanding the molecular bases of sweet taste is of crucial importance not only in biotechnology but also for its medical implications, since an increasing number of people is affected by food‐related diseases like, diabetes, hyperlipemia, caries, that are more or less directly linked to the secondary effects of sugar intake. Despite the interest paid to the field, it is only through the recent identification and functional expression of the receptor for sweet taste that new perspectives have been opened, drastically changing our approach to the development of new sweeteners. We shall give an overview of the field starting from the early days up to discussing the newest developments. After a review of early models of the active site, the mechanisms of interaction of small and macromolecular sweet molecules will be examined in the light of accurate modeling of the sweet taste receptor.

The analysis of the homology models of all possible dimers allowed by combinations of the human T1R2 and T1R3 sequences of the sweet receptor and the closed (A) and open (B) conformations of the mGluR1 glutamate receptor shows that only ‘type B’ sites, either T1R2(B) and T1R3(B), can host the majority of small molecular weight sweeteners. Simultaneous binding to the A and B sites is not possible with two large sweeteners but is possible with a small molecule in site A and a large one in site B. This observation accounted for the first time for the peculiar phenomenon of synergy between some sweeteners. In addition to these two sites, the models showed an external binding site that can host sweet proteins. Copyright © 2006 John Wiley & Sons, Ltd.
Electron ionization‐induced fragmentation of some new dibenzo(d, f)(1,3)dioxepine derivatives
Authors: Begala Michela , Tocco Graziella , Delogu Giovanna , Meli Gabriele , Picciau Carmen , Podda Gianni
Published: April 2006

The mass spectrometric behaviour of a series of 6,6‐disubstituted dibenzo(d,f)(1,3)dioxepine derivatives have been studied. The fragmentation patterns were described and discussed in detail with the aid of labelled compounds, accurate mass measurements and collisionally induced dissociation experiments performed using an ion trap. Copyright © 2006 John Wiley & Sons, Ltd.
Impact of global warming on ENSO variability using the coupled giss GCM/ZC model
Authors: Eichler Timothy , Rind David , Zebiak Stephen
Published: April 2006

This study uses a hybrid coupled model (referred to as the general‐circulation model (GCM)/Zebiak/Cane (ZC) model), which consists of the Goddard Institute for Space Studies' (GISS) Atmospheric general‐circulation model (AGCM) coupled to the oceanic component of the ZC intermediate model to assess the impact of global warming on El Niño behavior, with and without the influence of heat introduced from the subtropical Pacific (via subtropical cell (STC) pathway). The baseline GCM/ZC model produces El Niño variability with a two year periodicity and an amplitude of approximately half the magnitude of observed El Niño. The GCM/ZC model also produces an appropriate atmospheric global response to El Niño/southern oscillation (ENSO) as shown by composites of 500 hPa heights, sea‐level pressure (SLP), 200 hPa wind, and precipitation during El Niño and La Niña periods. To evaluate the importance of global warming on ENSO variability, 2× CO2 and 4× CO2 transient simulations were done increasing the atmospheric CO2 one percent per year, then extending the runs for an additional 70 years to obtain equilibrium climates for each run. An additional set of global‐warming simulations was run after including a STC parameterization generated by computing 5‐year running means of the sea‐surface temperature (SST) difference between a transient run and the 1× CO2 GCM/ZC run at the anticipated subduction zones (160–130°W, 20–40°N and 20–44°S, 160–130°W) and adding it to the base of the equatorial mixed‐layer of the ZC model with a time lag of 15 years. This effectively alters the vertical temperature gradient of the ZC model, which affects SST via upwelling.

Two features of the GCM/ZC response to global warming are emphasized. Firstly, the inclusion of the STC results in a major redistribution of heat across the equatorial Pacific, leading to an El Niño‐like response in the final equilibrium solution with less variability about the mean. The global warming aspect due to the El Niño‐like response results in a positive feedback on global warming, which causes a higher global surface‐air temperature (SAT) than identical transient simulations without inclusion of the STC. Secondly, including the STC effect produces a far greater magnitude of global ENSO‐like impact because of the reduction of, or even the reversal of, the equatorial Pacific longitudinal SST gradient. The implications of such an extreme climate scenario are discussed. Copyright © 2006 Royal Meteorological Society
Safety, Tolerability, and Efficacy of Everolimus in De Novo Liver Transplant Recipients: 12- and 36-Month Results
Authors: Levy Gary , Schmidli Heinz , Punch Jeffrey , Tuttle-Newhall Elizabeth , Mayer David , Neuhaus Peter , Samuel Didier , Nashan Bjorn , Klempnauer Juergen , Langnas Alan , Calmus Yvon , Rogiers Xavier , Abecassis Michael , Freeman Richard , Sloof Maarten , Roberts John , Fischer Lutz
Published: April 2006

Everolimus is a macrolide immunosuppressive agent with known consistent absorption. In this double-blind study, we examined the safety and tolerability of everolimus vs. placebo in de novo liver transplant recipients. One hundred and nineteen liver allograft recipients were randomized to 1 of 4 groups: everolimus 0.5 mg bid, everolimus 1.0 mg bid, everolimus 2 mg bid, or placebo. Patients received oral cyclosporine to achieve a target trough level of 150-400 ng/mL in combination with prednisone. Primary and secondary endpoints of safety, tolerability, and efficacy were determined at 12 months, and patients were followed through 36 months. There was a trend toward fewer treated acute rejections in the everolimus group than in the placebo group: everolimus 0.5 mg: 39.3%; everolimus 1.0 mg: 30.0%; everolimus 2 mg: 29.0%; placebo: 40.0% (P = not significant). Adverse events were higher in everolimus-treated patients especially at the 4-mg/day dose, but there was no difference in the incidence of thrombocytopenia or leukopenia between all groups and renal function as determined by serum creatinine, and creatinine clearance remained stable to 36 months in everolimus-treated patients. Mean cholesterol and triglycerides increased from baseline in all treatment groups, and maximum levels were seen at 6 months. In conclusion, this study demonstrates that everolimus in combination with oral cyclosporine had an acceptable safety and tolerability profile, paving the way for additional studies in this transplant indication.
Liver Transpl, 2006.

© 2006 AASLD.
The bounded approximation property for spaces of holomorphic mappings on infinite dimensional spaces
Authors: Çalışkan Erhan
Published: April 2006

We study the bounded approximation property for spaces of holomorphic functions. We show that if U is a balanced open subset of a Fréchet–Schwartz space or (DFM )‐space E , then the space ℋ︁(U ) of holomorphic mappings on U , with the compact‐open topology, has the bounded approximation property if and only if E has the bounded approximation property. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Infinitesimal deformations of double covers of smooth algebraic varieties
Authors: Cynk Sławomir , van Straten Duco
Published: April 2006

The goal of this paper is to give a method to compute the space of infinitesimal deformations of a double cover of a smooth algebraic variety. The space of all infinitesimal deformations has a representation as a direct sum of two subspaces. One is isomorphic to the space of simultaneous deformations of the branch locus and the base of the double covering. The second summand is the subspace of deformations of the double covering which induce trivial deformations of the branch divisor. The main result of the paper is a description of the effect of imposing singularities in the branch locus.

As a special case we study deformations of Calabi–Yau threefolds which are non‐singular models of double cover of the projective 3‐space branched along an octic surface. We show that in that case the number of deformations can be computed explicitly using computer algebra systems. This gives a method to compute the Hodge numbers of these Calabi–Yau manifolds. In this case the transverse deformations are resolutions of deformations of double covers of projective space but not double covers of a blow‐up of projective space. In the paper we gave many explicit examples. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Gustavsson–Peetre method for several Banach spaces
Authors: Fernández‐Martínez Pedro , González Luis , Romero Raúl
Published: April 2006

We extend the Gustavsson–Peetre method to the context of N ‐tuples of Banach spaces. We give estimates for the norm of the interpolated operator. The method is applied to tuples of weighted L p ‐spaces and to tuples of Orlicz spaces identifying the outcoming spaces in both cases. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Approximation numbers and Kolmogorov widths of Hardy‐type operators in a non‐homogeneous case
Authors: Edmunds D. E. , Lang J.
Published: April 2006

Let I = [a , b ] ⊂ ℝ, let 1 < q ≤ p < ∞, let u and v be positive functions with u ∈ L p ′ (I ) and v ∈ L q (I ), and let T : L p (I ) → L q (I ) be the Hardy‐type operator given by

equation image

Given any n ∈ ℕ, let s n stand for either the n ‐th approximation number of T or the n ‐th Kolmogorov width of T . We show that

equation image

where c pq is an explicit constant depending only on p and q . (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Enzyme‐Catalyzed Preparation of Aliphatic Polythioester by Direct Polycondensation of Diacid Diester and Dithiol
Authors: Kato Makoto , Toshima Kazunobu , Matsumura Shuichi
Published: April 2006

Summary: Aliphatic dithiol‐diacid type polythioesters were first enzymatically prepared by the direct polycondensation of hexane‐1,6‐dithiol and diacid diesters using the immobilized lipase from Candida antarctica (lipase CA). As a typical example, diethyl sebacate and hexane‐1,6‐dithiol were polymerized using lipase CA in bulk in the presence of molecular sieves 4A to produce the corresponding polythioester with an $\overline M _{\rm w}$ of 10 200 in 90% yield. Both the melting and crystallization temperatures of the produced polythioesters were higher when compared to those of the corresponding polyoxyesters. A higher molecular weight polythioester was produced using lipase in a two‐step procedure, i.e., cyclization with subsequent ring‐opening polymerization.

Preparation of polythioester and melting temperature of various polythioesters and polyoxyesters.

magnified image

Preparation of polythioester and melting temperature of various polythioesters and polyoxyesters.
Effect of Drawing Induced Dispersion of Nano‐Silica on Performance Improvement of Poly(propylene)‐Based Nanocomposites
Authors: Ruan Wen Hong , Huang Xian Bo , Wang Xian Hou , Rong Min Zhi , Zhang Ming Qiu
Published: April 2006

Summary: A new route that combines graft pre‐treatment and drawing techniques with melt mixing to prepare nanoparticle‐filled thermoplastic polymer composites is reported. Nano‐SiO2 particles are first modified by graft polymerization and then the grafted nanoparticles are melt‐compounded with poly(propylene) (PP) to produce composite filaments via drawing. Finally, the filaments are injection molded into bulk materials. Because the proposed manufacturing method is able to induce separation of the nanoparticles and the formation of beta‐crystals in the PP matrix, the resultant PP‐based nanocomposites are much tougher than the unfilled polymers, as characterized by either static or dynamic tests, in addition to showing a simultaneous increase in strength and stiffness.

Force–time curves of PP and its nanocomposites recorded during notch impact tests.

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Force–time curves of PP and its nanocomposites recorded during notch impact tests.
Regional brain volumes distinguish PSP, MSA‐P, and PD: MRI‐based clinico‐radiological correlations
Authors: Paviour Dominic C. , Price Shona L. , Jahanshahi Marjan , Lees Andrew J. , Fox Nick C.
Published: April 2006

Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are neurodegenerative disorders, each with a prevalence of around 5 per 100,000. Regional brain atrophy patterns differ in the two disorders, however, and magnetic resonance imaging is sometimes helpful in distinguishing them in the later stages. We measured whole brain and regional volumes, including cerebellum, pons, midbrain, superior cerebellar peduncle (SCP), and ventricular volumes as well as frontal and posterior–inferior cerebral regions in 18 subjects with PSP, 9 with MSA‐P (parkinsonian phenotype), 9 with Parkinson's disease (PD), and 18 healthy controls. Associations between these volumes, cognitive profiles, and clinical measures of disease severity and motor disability were assessed. Mean midbrain volume was 30% smaller in PSP than in PD or controls (P < 0.001) and 15% smaller than in MSA‐P (P = 0.009). The mean SCP volume in PSP was 30% smaller than in MSA‐P, PD, or controls (P < 0.001). Mean cerebellar volumes in MSA‐P were 20% smaller than in controls and PD and 18% smaller than in PSP (P = 0.01). Mean pontine volume in MSA‐P was 30% smaller than in PD or controls (P < 0.001) and 25% smaller than in PSP (P = 0.01). Motor disability was most strongly associated with midbrain volume, and more severe executive dysfunction was associated with reduced frontal volume. These distinct patterns of cortical and subcortical atrophy, when considered together rather than independently, better differentiate PSP and MSA‐P from each other and also from healthy controls. © 2006 Movement Disorder Society
Survival of Parkinson's disease patients in a large prospective cohort of male health professionals
Authors: Chen Honglei , Zhang Shumin M. , Schwarzschild Michael A. , Hernán Miguel A. , Ascherio Alberto
Published: April 2006

Parkinson's disease (PD) patients have higher mortality than individuals without PD. However, most of the previous studies were based on prevalent cases and few examined the potential effects of duration and smoking on the survival of PD patients. We compared the survival experience of 288 men with incident PD diagnosed between 1986 and 2000 with that of 51,012 men free of PD in the Health Professionals Follow‐up Study. As of January 2002, 92 deaths occurred among PD cases and 8,485 among men without PD. After controlling for age, men with PD had 60% higher mortality than those without PD (95% CI: 1.3–2.0). PD mortality was strongly related to disease duration: compared with men without PD, the age‐adjusted relative risk for PD patients was 1.1 during the first 5 years from diagnosis, 2.3 from 5 to 10 years, and 3.5 after 10 years (P < 0.0001 for trend). As expected, cigarette smoking was strongly and positively associated with total mortality among men free of PD (comparing >30 pack‐years vs. never smokers, relative risk, 2.0; P < 0.0001 for trend), but this association was not observed among PD patients (RR: 1.0; P = 0.95 for trend). This study confirms that PD patients have a higher mortality than individuals without PD and that the excess mortality increases with disease duration. However, smoking seems to impose little additional risk among PD patients in this large cohort of health professionals. © 2006 Movement Disorder Society
Thermal degradation kinetics of isoflavone aglycones from soy and red clover
Authors: Stintzing Florian Conrad , Hoffmann Manuel , Carle Reinhold
Published: April 2006

Driven by their beneficial effects on human metabolism, isoflavonoids have gained considerable importance reflected by an increased number of isoflavone‐rich foods, food supplements and pharmaceutical products on the market, mainly derived from soy and red clover. While it is well known that the genuine isoflavone pattern will be altered during processing, data on aglycone stability are rare. Therefore, a thorough study into the thermal sensitivities of biochanin A, daidzein, formononetin, flavone, genistein, glycitein and isoflavone was performed. Samples were heated at 150°C over a period of 7 h at three different pH values, and degradation of the aglycones was monitored by HPLC‐DAD analyses. Therefrom, structure‐related stability characteristics could be established. While virtually no decay was observed at pH 7.0 and 5.6, degradation was most prominent at pH 3. 1. Individual aglycone retention was further dependent on heating time with daidzein being the most labile compound after any time interval. Curve fitting of the data revealed first‐order degradation kinetics for flavone and glycitein, while the remaining aglycones exhibited a sigmoidal degradation pattern.
Fusarium mycotoxins and ochratoxin A in cereals and cereal products
Authors: Engelhardt Gabriele , Barthel Jörg , Sparrer Dieter
Published: April 2006

Results from the Bavarian Health and Food Safety Authority on contamination of cereals and cereal products from the Bavarian market with the mycotoxins deoxynivalenol (DON), zearalenone (ZEA), and ochratoxin A (OTA) and of maize meal and semolina with fumonisins (FUM) in the year 2004 are presented. Contamination rates and levels of DON, ZEA, and OTA were low and did not exceed the maximum levels. However, a 92% contamination rate and high levels of FUM in maize meal and semolina were measured. Contamination levels of mycotoxins are discussed and evaluated with respect to possible health implications for consumers.
Stimulation of estradiol glucuronidation: A protective mechanism against estradiol‐mediated carcinogenesis?
Authors: Pfeiffer Erika , Graf Eva , Gerstner Silke , Metzler Manfred
Published: April 2006

17β‐Estradiol (E2) and its catechol and methoxy metabolites are believed to play important roles in the mechanism of E2–mediated tumor formation. Because conjugation with glucuronic acid lowers tissue levels by facilitating excretion, we have determined the kinetic parameters of the glucuronidation of E2, estrone (E1), and seven phase I metabolites using human liver microsomes. The catechol estrogens 2‐ and 4‐hydroxy‐E2/E1 exhibited the highest clearance, exceeding that of E2, E1, and the methoxy metabolites by factors of 6–44. Homotropic activation kinetics were observed for the 3‐glucuronidation of E2 but not for any of the metabolites. None of the metabolites affected the kinetics of the 3‐glucuronidation of E2. In contrast, the isoflavone daidzein stimulated the formation of E2‐3‐glucuronide, as has been reported previously. This heterotropic activation by daidzein appears to be specific for the glucuronidation of E2 because daidzein did not affect the glucuronidation of the 2‐ and 4‐hydroxy metabolites of E2. However, daidzein may lower the glucuronidation of 2‐methoxy‐E2in vivodue to its preferential glucuronidation. The decreased tissue levels of E2 and increased concentrations of 2‐methoxy‐E2, as implied by this study and the previous one, may contribute to the protective effect of daidzein against breast and endometrial cancer.
Cytotoxic and antimitotic effects of N‐containing Monascus metabolites studied using immortalized human kidney epithelial cells
Authors: Knecht Anja , Humpf Hans‐Ulrich
Published: April 2006

Recently the first Monascus metabolites with a pyridine ring were detected, the monascopyridines A and B. They are formally dehydrogenated derivatives of the red rice pigments rubropunctamine and monascorubramine. Because of their structural similarity, the toxicological effects of these secondary metabolites were studied using immortalized human kidney epithelial cells. The cytotoxicity was determined with the following different endpoint detection methods: metabolic activity, trypan blue exclusion, and electronic cell counting. The compounds led to EC50 values between 11 and 31 μmol/L but the pigments caused a stronger reduction of the cell viability. Also, the apoptotic potential was examined by measuring caspase 3 activity and detecting apoptotic bodies, but none of the tested compounds induced apoptosis. All four substances caused a rise of the mitotic index to about 9% (100 μmol/L monascopyridine A and B) and 20% (25 μmol/L rubropunctamine and monascorubramine). The significant decrease of the ratio of cells in the ana‐ and telophase to cells in the prometa‐ and metaphase proved a stop of the mitosis at the meta‐ to anaphase control point. The compounds caused mitotic arrest and the formation of structural damages like c‐mitosis through interaction with the mitotic spindle. These effects point to an aneuploidy inducing potential, which is linked to cancer formation.
Structure elucidation of a new friedelane triterpene from the mangrove plant Hibiscus tiliaceus
Authors: Li Liya , Huang Xueshi , Sattler Isabel , Fu Hongzheng , Grabley Susanne , Lin Wenhan
Published: April 2006

From the stem and bark of the mangrove plant Hibiscus tiliaceus, a new friedelane‐type triterpene named 27‐oic‐3‐oxo‐28‐friedelanoic acid (1) together with eight known triterpenoids involving five friedelane‐type derivatives was isolated. The structure of 1 was determined by extensive 2D NMR (DQF‐COSY, HMQC, HMBC, and NOESY) data analyses. All the compounds were obtained from mangrove plants for the first time. Copyright © 2006 John Wiley & Sons, Ltd.
Correction of systematic errors in CORE processing of DOSY data
Authors: Nilsson Mathias , Morris Gareth A.
Published: April 2006

DOSY data for mixtures are commonly processed either by single channel methods (e.g. HR‐DOSY) or multichannel methods (e.g. CORE). Both aim to separate the signals from species of different molecular sizes by their diffusion coefficients; the result is displayed either as a 2D plot (as in HR‐DOSY) or as individual spectra (as in CORE). Both types of methods are sensitive to any systematic errors in the experimental data. The effects of, and remedies for, two such sources of error, spatially non‐uniform pulsed field gradients (PFGs) and instrument instability, are demonstrated for CORE processing, using a corrected form of the Stejskal–Tanner equation and reference deconvolution, respectively. Copyright © 2006 John Wiley & Sons, Ltd.
Solvent effect in 1H NMR spectra of 3′‐hydroxy‐4′‐methoxy isoflavonoids from Astragalus membranaceus var. mongholicus
Authors: Du Xingang , Bai Yanjing , Liang Hong , Wang Zhiying , Zhao Yuying , Zhang Qingying , Huang Luqi
Published: April 2006

Four 3′‐hydroxy‐4′‐methoxy‐isoflavonoids: calycosin‐7‐O‐β‐D‐glucopyranoside (1), calycosin (2), pratensein‐7‐O‐β‐D‐glucopyranoside (3), and pratensein (4) were isolated from Astragalus membranaceus var. mongholicus, among which compound 4 was obtained from this plant for the first time. The solvent effect obscuring 1H signal patterns of B ring of compounds 1–4 was reported to avoid mis‐assignments. Previously reported NMR data of compounds 1 and 2 were corrected based on 1D and 2D NMR experiments. Copyright © 2006 John Wiley & Sons, Ltd.
Density‐functional computation of 53Cr NMR chemical shifts
Authors: Bühl Michael
Published: April 2006

53Cr chemical shifts of CrO42−, Cr2O72−, CrO3X−, CrO2X2(X = F, Cl), and Cr(CO)5L (L = CO, PF3, CHNH2, CMeNMe2) are computed, using geometries optimized with the gradient‐corrected BP86 density functional, at the gauge‐including atomic orbitals (GIAO)‐, BPW91‐, and B3LYP levels. For this set of compounds, substituent effects on δ(53Cr) are better described with the pure BPW91 functional than with B3LYP, in contrast to most other transition‐metal chemical shifts studied so far. For selected cases, 53Cr NMR line widths can be rationalized in terms of electric field gradients (EFGs) computed with the BPW91 functional, but in general other factors such as molecular correlation times appear to be dominating. 53Cr chemical shifts and EFGs are predicted for CrO3, Cr(C6H6)2, Cr(C6H6)CO3, and, with reduced reliability, for Cr2(µ2‐O2CH)4. Copyright © 2006 John Wiley & Sons, Ltd.