bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytochrome P450 enzymes and the heart
Authors: Chaudhary Ketul R. , Batchu Sri Nagarjun , Seubert John M.
Published: September 2009

The cytochrome P450 monooxygenase system (CYP) is a multigene superfamily of heme‐thiolate enzymes, which are important in the metabolism of foreign and endogenous compounds. Genetic variations, drug interactions, or pathophysiological factors can lead to reduced, absent, or increased enzymatic activity. This altered CYP activity greatly influences an individual's response to therapeutic treatment. What is not known is the impact of these changes on the many functional roles of CYP in physiological and pathophysiological processes of the heart. Many extrahepatic tissues, like heart, contain active P450 enzymes but lack information regarding their role in cellular injury or homeostasis. Much of our current knowledge about cardiac CYP has been limited to studies investigating the role of fatty acid metabolites in heart. Traditional risk factors including diabetes, smoking, and hypertension have well established links to cardiovascular disease. And new evidence strongly suggests exposure to chemicals and other environmental agents has a profound impact on the cardiovascular system. These risk factors can independently affect the expression and activity of CYP enzymes. Therefore, altered CYP activity is important from a detoxification as well as a bioactivation perspective. Considering CYP, interactions are greatly dependent on inherited differences or acquired changes in enzyme activity further research into their potential impact on pathogenesis, risk assessment, and therapy of heart disease is warranted. This review explores the expression of CYP isoforms, their functional roles, and the effects of genetic variation in the heart. © 2009 IUBMB IUBMB Life, 61(10): 954–960, 2009
Aquaporin‐1 activity of plasma membrane affects HT20 colon cancer cell migration
Authors: Jiang Yong
Published: September 2009

Recent studies revealed an important role of aquaporins (AQPs) in cell migration and migration‐associated cell function such as angiogenesis, wound healing, and neutrophil motility. Migration of tumor cells is a crucial step in tumor invasion and metastasis. In the present study, we investigated the expression of AQP1 in human HT20 colon cancer cells and characterized its function in cell migration. By reverse transcription–polymerase chain reaction (RT‐PCR) and immunoblot analysis, expression of AQP1 was identified in HT20 cell lines. Immunofluorescence analysis indicated expression of AQP1 protein in the plasma membrane of HT20 cells. The recombinant adenovirus expressing human AQP1 increased the mRNA and protein expression of AQP1 in HT20 cells. In contrary, the RNA interference vector of AQP1 effectively inhibited the mRNA and protein expression of AQP1 in HT20 cells. Adenovirus‐mediated high expression of AQP1 in HT20 cells increased relative plasma membrane water permeability and migration rate in both wound healing and invasive transwell migration assays. In contrary, RNA interference vector‐mediated low expression of AQP1 in HT20 cells reduced relative plasma membrane water permeability and migration rate. AQP1 expression induced relocalization of actin protein and activation of RhoA and Rac. In nude mice, AQP1 increased extravasation of HT20 Cells in lung after tail vein injection. The results provided the direct evidence that aquaporin‐mediated plasma membrane water permeability plays an important role in colon cancer cell migration and may be associated with colon cancer invasion and metastasis. © 2009 IUBMB IUBMB Life, 61(10): 1001–1009, 2009
Molecular biology of KATP channels and implications for health and disease
Authors: Alejandro Akrouh , S. Eliza Halcomb , Colin G. Nichols , Monica Sala‐Rabanal
Published: September 2009

The ATP‐sensitive potassium (KATP) channel is expressed in most excitable tissues and plays a critical role in numerous physiological processes by coupling intracellular energetics to electrical activity. The channel is comprised of four Kir6.x subunits associated with four regulatory sulfonylurea receptors (SUR). Intracellular ATP acts on Kir6.x to inhibit channel activity, while MgADP stimulates channel activity through SUR. Changes in the cytosolic [ATP] to [ADP] ratio thus determine channel activity. Multiple mutations in Kir6.x and SUR genes have implicated KATP channels in various diseases ranging from diabetes and hyperinsulinism to cardiac arrhythmias and cardiovascular disease. Continuing studies of channel physiology and pathology will bring new insights to the molecular basis of KATP channel function, leading to a better understanding of the role that KATP channels play in both health and disease. © 2009 IUBMB IUBMB Life, 61(10): 971–978, 2009
The potential of biophotonic techniques in stem cell tracking and monitoring of tissue regeneration applied to cardiac stem cell therapy
Authors: Wilson Brian C. , Vitkin I. Alex , Matthews Dennis L.
Published: September 2009

The use of injected stem cells, leading to regeneration of ischemic heart tissue, for example, following coronary artery occlusion, has emerged as a major new option for managing ‘heart attack’ patients. While some clinical trials have been encouraging, there have also been failures and there is little understanding of the multiplicity of factors that lead to the outcome. In this overview paper, the opportunities and challenges in applying biophotonic techniques to regenerative medicine, exemplified by the challenge of stem cell therapy of ischemic heart disease, are considered. The focus is on optical imaging to track stem cell distribution and fate, and optical spectroscopies and/or imaging to monitor the structural remodeling of the tissue and the resulting functional changes. The scientific, technological, and logistics issues involved in moving some of these techniques from pre‐clinical research mode ultimately into the clinic are also highlighted. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Introduction: The policy trajectory of fair trade
Authors: Fisher Eleanor
Published: September 2009

This paper provides a selective review of literature on fair trade and introduces contributions to this Policy Arena. It focuses on policy practice as a dynamic process, highlighting the changing configurations of actors, policy spaces, knowledge, practices and commodities that are shaping the policy trajectory of fair trade. It highlights how recent literature has tackled questions of mainstreaming as part of this trajectory, bringing to the fore dimensions of change associated with the market, state and civil society. Copyright © 2009 John Wiley & Sons, Ltd.
Inhomogeneity of rat vertebrae trabecular architecture by high‐field 3D μ‐magnetic resonance imaging and variable threshold image segmentation
Authors: Palombarini Marcella , Gombia Mirko , Fantazzini Paola , Giardino Roberto , Giavaresi Gianluca , Parrilli Annapaola , Vittur Franco , Guillot Genevieve
Published: September 2009

Purpose

To analyze the 3D microarchitecture of rat lumbar vertebrae by micro‐magnetic resonance imaging (μ‐MRI).

Materials and Methods

μ‐MR images (20 × 20 × 20 μm3 apparent voxel size) were acquired with a three‐dimensional spin‐echo pulse sequence on four lumbar vertebrae of two rats. Apparent microarchitectural parameters like trabecular bone fraction (BV/TV), specific bone surface (BS/TV), mean intercept length (MIL), and Euler number per unit volume (Euler density, EV) were calculated using a novel semiquantitative variable threshold segmentation technique. The threshold value T* was obtained as a point of minimum or maximum of the function EV = EV(T).

Results

Quantitative 3D analysis of μ‐MRI images revealed a higher connectivity in the peripheral regions (EV = −570 ± 70 mm−3) than in the central regions (EV = −130 ± 50 mm−3) of the analyzed rat lumbar vertebrae. Smaller intertrabecular cavities and larger bone volume fractions were observed in peripheral regions as compared to central ones (MIL = 0.18 ± 0.01 mm and 0.26 ± 0.01 mm; BV/TV = 34 ± 3% and 29 ± 3%, respectively). The quantitative 3D study of MIL showed a structural anisotropy of the trabeculae along the longitudinal axis seen on the images. The inhomogeneity of the bone architecture was validated by micro‐computed tomography (μ‐CT) images at the same spatial resolution.

Conclusion

3D high‐field μ‐MRI is a suitable technique for the assessment of bone quality in experimental animal models. J. Magn. Reson. Imaging 2009;30:825–833. © 2009 Wiley‐Liss, Inc.
Quantitative multivoxel proton spectroscopy of the brain in developmental delay
Authors: Verbruggen Krijn T. , Maurits Natasha M. , Meiners Linda C. , Brouwer Oebele F. , van Spronsen Francjan J. , Sijens Paul E.
Published: September 2009

Purpose

To assess whether proton MR spectroscopy of the brain in children with developmental delay reveals a consistent pattern of abnormalities.

Materials and Methods

Eighty‐eight patients (median age, 4.6 years; interquartile range, 3.1–8.1 years) with unexplained developmental delay, were compared with 48 normally developing age‐matched controls. Patients and controls were assigned to five age‐groups. Multivoxel MR spectroscopy was performed on a volume of interest superior to the lateral ventricles. The relative levels of choline, creatine, N‐acetyl aspartate, and glutamate/glutamine in 24 voxels containing white matter and 12 voxels containing gray matter were quantified in an operator‐independent manner and expressed in proportion to the total metabolite peak area in the volume of interest.

Results

White matter choline in DD showed less decrease with age. Mean choline levels, compared with mean control levels, increased from 99 to 111% with increasing age. This was statistically significant in the highest age groups (P = 0.015 [7 < yr ≤ 12.8] and P = 0.039 [12.8 < yr]). Other metabolites did not show clear alterations.

Conclusion

Proton MR spectroscopy in a group of patients with unexplained DD shows small differences in the metabolite pattern, compared with normally developing controls, that is, higher choline in the white matter. The pathophysiological origin and significance may relate to myelination and maturation of the white matter. J. Magn. Reson. Imaging 2009;30:716–721. © 2009 Wiley‐Liss, Inc.
Dilution method of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI)
Authors: Motosugi Utaroh , Ichikawa Tomoaki , Sou Hironobu , Sano Katsuhiro , Ichikawa Shintaro , Tominaga Licht , Araki Tsutomu
Published: September 2009

Purpose

To elucidate whether a contrast agent dilution method (dilution method), in which gadoxetate disodium (Gd‐EOB‐DTPA) is diluted with saline, is useful for good‐quality arterial‐phase images.

Materials and Methods

In this study we observed 494 hypervascular hepatocellular carcinomas (HCCs) in 327 patients with chronic liver disease. Three Gd‐EOB‐DTPA injection methods were adopted for comparison: 1) test injection method (undiluted Gd‐EOB‐DTPA and modified scan delay), in which a test dose of 0.5 mL of Gd‐EOB‐DTPA was injected to determine scan delay; 2) conventional method (undiluted Gd‐EOB‐DTPA and fixed scan delay); and (3) dilution method (diluted Gd‐EOB‐DTPA and fixed scan delay), in which Gd‐EOB‐DTPA was diluted to 20 mL with saline. Lesion‐liver contrast was calculated. Image quality and lesion detectability were evaluated by two radiologists blinded to the injection methods.

Results

The lesion‐liver contrast of the dilution method was significantly higher than that of the other two methods. Lesion detectability of the conventional method (64%) was significantly lower than that of the other two methods (contrast agent dilution method, 95%; test injection method, 93%). The image quality of the contrast agent dilution method was significantly better than that of the other two methods.

Conclusion

The dilution method contributed to improved image quality, high lesion‐liver contrast, and high lesion detectability in the arterial‐phase images of GD‐EOB‐DTPA‐enhanced MRI. J. Magn. Reson. Imaging 2009;30:849–854. © 2009 Wiley‐Liss, Inc.
In vivo DTI assessment of hepatic ischemia reperfusion injury in an experimental rat model
Authors: Cheung Jerry S. , Fan Shu Juan , Chow April M. , Hui Edward S. , Wu Ed X.
Published: September 2009

Purpose

To investigate hepatic ischemia reperfusion injury (IRI) using diffusion tensor imaging (DTI).

Materials and Methods

Ten Sprague‐Dawley rats were scanned at 7 Tesla (T) with DTI using b‐value of 1000 s/mm2 and 6 gradient directions before, 2 h, and 1 day after 30‐min total hepatic IRI. Apparent diffusion coefficient or mean diffusivity (MD), directional diffusivities and fractional anisotropy (FA) were measured. Seven of the animals were also examined with spin‐echo echo‐planar diffusion‐weighted imaging (DWI) with seven b‐values up to 2000 s/mm2 to estimate the true diffusion coefficient (D), blood pseudodiffusion coefficient (D*), and perfusion fraction (f) using a bi‐compartmental model.

Results

MD 2 h after IRI (0.77 ± 0.07 × 10−3 mm2/s) was significantly lower (P < 0.01) than that before (1.03 ± 0.07 × 10−3 mm2/s) and 1 day after IRI (1.01 ± 0.05 × 10−3 mm2/s). Meanwhile, FA 2 h after IRI (0.33 ± 0.03) was significantly higher (P < 0.01) than that before (0.21 ± 0.02) and 1 day after IRI (0.20 ± 0.02). The bi‐compartmental model analysis revealed the transient decrease in D, D* and f 2 h after IRI. Liver histology showed the multifocal cell swelling 3 h after IRI and widespread cell necrosis/apoptosis 1 day after IRI. Sinusoidal narrowing and congestion of erythrocytes were also observed 3 h and 1 day after IRI.

Conclusion

DTI can characterize hepatic IRI by detecting the transient change in both MD and FA. J. Magn. Reson. Imaging 2009;30:890–895. © 2009 Wiley‐Liss, Inc.
Raman spectra of a pseudo‐oxocarbon anion in ionic liquids
Authors: Garcia Humberto C. , de Oliveira Luiz F. C. , Ribeiro Mauro C. C.
Published: September 2009

Raman and electronic spectra of the [3,5‐bis(dicyanomethylene)cyclopentane‐1,2,4‐trionate] dianion, the croconate violet (CV), are reported in solutions of ionic liquids based on imidazolium cations. Different normal modes of the CV anion, ν (CO), ν (CO) + ν (CC) + ν (CCN), and ν(C≡N), were used as probes of solvation characteristics of ionic liquids, and were compared with spectra of CV in common solvents. The spectra of CV in ionic liquids are similar to those in dichloromethane solution, but distinct from those in protic solvents such as ethanol or water. The UV–vis spectra of CV in ionic liquids strongly suggest π–π interactions between the CV anion and the imidazolium cation. Copyright © 2009 John Wiley & Sons, Ltd.
Effects of organic fertilisers and irrigation level on physical and chemical quality of industrial tomato fruit (cv. Nautilus)
Authors: Madrid Ramón , Barba Eva Maria , Sánchez Antonio , García Antonio Lino
Published: September 2009

BACKGROUND: The objective of this work was to study the influence of irrigation and organic fertilisation on quality attributes of tomato fruit (cv. Nautilus) grown for the canning industry. The assay was carried out during two consecutive years (2006 and 2007) in agricultural soil. Nine treatments resulting from the combination of three fertilisation types (sheep manure, a mixture of sheep manure and peat and an inorganic fertiliser (control)) with three levels of drip irrigation (3.30, 5.00 and 6.70 mm day−1) under black polyethylene mulch were applied (n = 3).

RESULTS: For the chromatic attributes L*, H*, C* and S* the highest values corresponded to the treatments with organic matter. However, the a*/b* ratio and colour index value were higher for the control treatment. In all cases the estimated optimal ripening time was the same, and on this date a decline in the ratios was observed. The values of the physical properties increased with increasing irrigation, higher values always being obtained in the treatments with organic fertilisers. The highest production for all irrigation levels corresponded to the treatment with mixed sheep manure and peat fertiliser.

CONCLUSION: Cultivation involving fertilisation with the manure/peat mixture and an irrigation level slightly above 5.00 mm day−1 can be recommended as optimal, since it gave the most satisfactory values with respect to the quality attributes of tomato fruit grown for the canning industry. Copyright © 2009 Society of Chemical Industry
Long-term management after liver transplantation: Primary care physician versus hepatologist
Authors: Heller Christie J. , Prochazka Allan V. , Everson Gregory T. , Forman Lisa M.
Published: September 2009

As long-term survival after liver transplantation increases, metabolic complications are becoming increasingly prevalent. Given concerns about which group of providers should be managing liver recipients and how well metabolic complications are managed, we administered a postal survey to 280 transplant hepatologists to determine attitudes, perceptions, and practice patterns in the management of metabolic complications after transplantation. The response rate was 68.2%. There was great variation in patterns of practice across the United States with respect to the number of posttransplant clinics, clinic format, and number of recipients cared for per week. Hepatologists, primary care physicians (PCPs), and surgeons were primarily responsible for the overall care of liver recipients 1 year or more after liver transplantation according to 66%, 24%, and 8% of respondents, respectively. Hepatologists felt that metabolic complications were common, but few strongly agreed that hypertension (33.3%), chronic renal insufficiency (3.8%), diabetes mellitus (8.8%), dyslipidemia (11.1%), and bone disease (12.8%) were well controlled. The majority of hepatologists indicated that ideally PCPs should be managing recipients' hypertension, diabetes mellitus, dyslipidemia, and bone disease (78.8%, 63.1%, 78.3%, and 72.5%), but they felt that in actuality, PCPs were managing these conditions less frequently (45.4%, 51.4%, 44.6%, and 38%). In conclusion, metabolic complications are perceived to be common but not well controlled post-transplant, and most hepatologists feel that PCPs should take a more active role in the management of these complications. Future studies are needed to identify barriers to care in the treatment of metabolic complications post-transplant with the goal of improving long-term morbidity and mortality. Liver Transpl 15:1330–1335, 2009. © 2009 AASLD.
Conversion from a calcineurin inhibitor to everolimus therapy in maintenance liver transplant recipients: A prospective, randomized, multicenter trial
Authors: De Simone Paolo , Metselaar Herold J. , Fischer Lutz , Dumortier Jérôme , Boudjema Karim , Hardwigsen Jean , Rostaing Lionel , De Carlis Luciano , Saliba Faouzi , Nevens Frederik
Published: September 2009

Calcineurin inhibitors (CNIs) contribute to renal dysfunction following liver transplantation. This prospective, randomized, multicenter, 6-month study (with an additional 6 months of follow-up) evaluated whether everolimus with CNI reduction or discontinuation would improve renal function in maintenance liver transplant recipients experiencing CNI-related renal impairment. Patients started everolimus therapy with CNI reduction or discontinuation (n = 72) or continued receiving standard-exposure CNI (n = 73). At month 6, 80% of the patients who had converted to everolimus had discontinued the CNI. The mean change in creatinine clearance (CrCl) from baseline to month 6 was similar between groups (everolimus, 1.0 ± 10.2 mL/minute; controls, 2.3 ± 7.8 mL/minute; P = 0.46), so the primary study endpoint (8 mL/minute difference in the change in CrCl) was not achieved. Among patients who continued everolimus according to the protocol, the mean increase in CrCl was 2.1 (n = 53) and 3.8 mL/minute (n = 38) at months 6 and 12, respectively, versus 2.4 (n = 68) and 3.5 mL/minute in controls (n = 51). The high frequency of CNI dose reductions in controls (77% of the patients) and the relatively long mean time post-transplant (>3 years) likely contributed to the small difference in CrCl. Biopsy-proven acute rejection occurred in 1.4% of the patients in each group, with no graft losses. Study drug discontinuation was higher in everolimus-treated patients, and adverse events were more frequent. These data demonstrate that everolimus allows for discontinuation or a major reduction of CNI exposure in liver allograft recipients suffering CNI-related renal dysfunction without a loss of efficacy. Trials targeting earlier conversion post-transplantation are required to confirm the efficacy and safety of everolimus for improving renal function after liver transplantation. Liver Transpl 15:1262–1269, 2009. © 2009 AASLD.
Recipient age affects long-term outcome and hepatitis C recurrence in old donor livers following transplantation
Authors: Selzner Markus , Kashfi Arash , Selzner Nazia , McCluskey Stuart , Greig Paul D. , Cattral Mark S. , Levy Gary A. , Lilly Les , Renner Eberhard L. , Therapondos George , Adcock Lesley E. , Grant David R. , McGilvray Ian D.
Published: September 2009

We studied the role of donor and recipient age in transplantation/ischemia-reperfusion injury (TIRI) and short- and long-term graft and patient survival. Eight hundred twenty-two patients underwent deceased donor liver transplantation, with 197 donors being ≥60 years old. We evaluated markers of reperfusion injury, graft function, and clinical outcomes as well as short- and long-term graft and patient survival. Increased donor age was associated with more severe TIRI and decreased 3- and 5-year graft survival (73% versus 85% and 72% versus 81%, P < 0.001) and patient survival (77% versus 88% and 77% versus 82%, P < 0.003). Hepatitis C virus (HCV) infection and recipient age were the only independent risk factors for graft and patient survival in patients receiving an older graft. In the HCV(+) cohort (297 patients), patients ≥ 50 years old who were transplanted with an older graft versus a younger graft had significantly decreased 3- and 5-year graft survival (68% versus 83% and 64% versus 83%, P < 0.009). In contrast, HCV(+) patients < 50 years old had similar 3- and 5-year graft survival if transplanted with either a young graft or an old graft (81% versus 82% and 81% versus 82%, P = 0.9). In conclusion, recipient age and HCV status affect the graft and patient survival of older livers. Combining older grafts with older recipients should be avoided, particularly in HCV(+) patients, whereas the effects of donor age can be minimized in younger recipients. Liver Transpl 15:1288–1295, 2009. © 2009 AASLD.
The use of preoperative nutritional interventions to protect against hepatic ischemia-reperfusion injury
Authors: van Ginhoven Tessa M. , Mitchell James R. , Verweij Marielle , Hoeijmakers Jan H. J. , Ijzermans Jan N. M. , de Bruin Ron W. F.
Published: September 2009

Preoperative fasting was introduced in the 19th century to reduce the risk of aspiration pneumonia while patients were under general anesthesia. During the last decades, the value of preoperative fasting has been questioned, and more liberal guidelines have been proposed, such as the use of preoperative carbohydrate-rich drinks. Here we review both old and new evidence supporting the view that fasting slightly longer than overnight is beneficial for an entirely different purpose: protection against certain types of stress, such as ischemia-reperfusion injury. We provide a framework to explain these benefits as well as future applications and alternatives that could be used to induce the protection afforded by nutritional interventions. Liver Transpl 15:1183–1191, 2009. © 2009 AASLD.
Preconditioning, organ preservation, and postconditioning to prevent ischemia-reperfusion injury to the liver
Authors: de Rougemont Olivier , Lehmann Kuno , Clavien Pierre-Alain
Published: September 2009

Ischemia and reperfusion lead to injury of the liver. Ischemia-reperfusion injury is inevitable in liver transplantation and trauma and, to a great extent, in liver resection. This article gives an overview of the mechanisms involved in this type of injury and summarizes protective and treatment strategies in clinical use today. Intervention is possible at different time points: during harvesting, during the period of preservation, and during implantation. Liver preconditioning and postconditioning can be applied in the transplant setting and for liver resection. Graft optimization is merely possible in the period between the harvest and the implantation. Given that there are 3 stages in which a surgeon can intervene against ischemia-reperfusion injury, we have structured the review as follows. The first section reviews the approaches using surgical interventions, such as ischemic preconditioning, as well as pharmacological applications. In the second section, static organ preservation and machine perfusion are addressed. Finally, the possibility of treating the recipient or postconditioning is discussed. Liver Transpl 15:1172–1182, 2009. © 2009 AASLD.
Variability of extreme rainfall events over India during southwest monsoon season
Authors: Pattanaik D. R. , Rajeevan M.
Published: September 2009

The spatial and temporal variability of extreme rainfall events over India and their long‐term trend have been analysed during the southwest monsoon season from June to September (JJAS) by taking daily rainfall data for 55 years (1951–2005). The contribution of extreme rainfall events (Category iii with rainfall > 124.4 mm day−1) to the total seasonal rainfall is also analysed for the same period. The analysis shows that the occurrence of extreme rainfall events over India during JJAS shows spatial variations with preferred regions of occurrence over the west coast, central parts of India and northeast India. The average frequency of extreme rainfall events along with the contribution of extreme rainfall events to the seasonal rainfall shows a significant increasing trend (above the 98% confidence level) over the Indian region during JJAS, and also during June and July. It is also found that the increasing trend of contribution from extreme rainfall events during JJAS is balanced by a decreasing trend in Category i (rainfall ≤ 64.4 mm day−1) rainfall events. Using the filtered data it is found that the increasing trend of extreme rainfall over central India is mainly contributed by synoptic scale systems (periodicity between 3 and 7 days). The seasonal mean moist convective instability (CI) during JJAS averaged over central India indicates a significant increasing trend (99.9% confidence level) and is basically due to the increasing trend of the number of days with greater degree of moist CI during JJAS, which may be one possible cause for the increasing trend in the frequency of extreme rainfall events over the region. Copyright © 2009 Royal Meteorological Society
Xenotransplantation, Xenogeneic Infections, Biotechnology, and Public Health
Authors: Chapman Louisa E.
Published: September 2009

Xenotransplantation is the attempt to use living biological material from nonhuman animal species in humans for therapeutic purposes. Clinical trials and preclinical studies have suggested that living cells and tissue from other species have the potential to be used in humans to ameliorate disease. However, the potential for successful xenotransplantation to cure human disease is coupled with the risk that therapeutic use of living nonhuman cells in humans may also serve to introduce xenogeneic infections of unpredictable significance. Animal husbandry practices and xenotransplantation product preparation may eliminate most exogenous infectious agents prior to transplantation. However, endogenous retroviruses are present in the genomes of all mammalian cells, have an inadequately defined ability to infect human cells, and have generated public health concern. The history of xenotransplantation, the implications for public health, the global consensus on public safeguards necessary to accompany clinical trials, and the future direction of xenotransplantation are discussed in the context of public health. Mt Sinai J Med 76:435–441, 2009. © 2009 Mount Sinai School of Medicine
Surveillance and Control of Zoonotic Agents Prior to Disease Detection in Humans
Authors: Childs James E. , Gordon Elizabeth R.
Published: September 2009

The majority of newly emerging diseases are zoonoses caused by pathogens transmitted directly or indirectly through arthropod vectors to humans. Transmission chains leading to human infection frequently involve intermediate vertebrate hosts, including wildlife and domestic animals. Animal‐based surveillance of domestic and wild animals for zoonotic pathogens is a global challenge. Until recently, there has been no scientific, social, or political consensus that animal‐based surveillance for zoonotic pathogens merits significant infrastructural investment, other than the fledgling efforts with avian influenza. National institutions charged with strategic planning for emerging diseases or intentional releases of zoonotic agents emphasize improving diagnostic capabilities for detecting human infections, modifying the immune status of human or domestic animals through vaccines, producing better antiviral or antibacterial drugs, and enhancing human‐based surveillance as an early warning system. With the exception of human vaccination, these anthropocentric approaches target post‐spillover events, and none of these avenues of research will reduce the risk of additional emergences of pathogens from wildlife. Novel schemes for preventing spillover of human pathogens from animal reservoir hosts can spring only from an understanding of the ecological context and biological interactions that result in zoonotic disease emergence. Although the benefits derived from investments to improve surveillance and knowledge of zoonotic pathogens circulating among wildlife reservoir populations are uncertain, our experience with human immunodeficiency virus and the pandemic influenza inform us of the outcomes that we can expect by relying on detection of post‐spillover events among sentinel humans. Mt Sinai J Med 76:421–428, 2009. © 2009 Mount Sinai School of Medicine
Historical Perspectives on Malaria: The Rockefeller Antimalaria Strategy in the 20th Century
Authors: Stapleton Darwin H.
Published: September 2009

Malaria, a serious disease for all of human history, was not effectively handled until methods for control of its insect vector, theAnophelesmosquito, were developed at the beginning of the 20th century. The Rockefeller Foundation's antimalaria program spread vector‐control strategies throughout the world, and its adoption of dichlorodiphenyltrichloroethane during World War II created an especially powerful and effective malaria control strategy. However, insect resistance to dichlorodiphenyltrichloroethane and restrictions on dichlorodiphenyltrichloroethane use due to its long‐term environmental effects are factors in the persistence of malaria as a serious health problem. Mt Sinai J Med 76:468–473, 2009. © 2009 Mount Sinai School of Medicine
The Significant but Understudied Impact of Pathogen Transmission from Humans to Animals
Authors: Epstein Jonathan H. , Price Joan T.
Published: September 2009

Zooanthroponotic pathogens, which are transmitted from humans to nonhuman animals, are an understudied aspect of global health, despite their potential to cause significant disease burden in wild and domestic animal populations and affect global economies. Some key human‐borne pathogens that have been shown to infect animals and cause morbidity and mortality include measles virus (paramyxoviruses), influenza A virus (orthomyxoviruses), herpes simplex 1 virus (herpesviruses), protozoal and helminthic parasites, and bacteria such as methicillin‐resistantStaphylococcus aureusandMycobacterium tuberculosis. However, zooanthroponotic pathogens are most commonly reported in captive animals or domestic livestock with close human contact; there, the potential for economic loss and human reinfection is most apparent. There is also the potential for infection in wild animal populations, which may threaten endangered species and decrease biodiversity. The emergence and reemergence of human‐borne pathogens in wildlife may also have negative consequences for human health if these pathogens cycle back into humans. Many of the anthropogenic drivers of zoonotic disease emergence also facilitate zooanthroponotic transmission. Increasing research to better understand the occurrence of and the potential for bidirectional pathogen transmission between humans and animals is essential for improving global health. Mt Sinai J Med 76:448–455, 2009. © 2009 Mount Sinai School of Medicine
The effect of intravesical oxybutynin on the ice water test and on electrical perception thresholds in patients with neurogenic detrusor overactivity
Authors: Van Meel Tom David , De Wachter Stefan , Wyndaele Jean Jacques
Published: September 2009

Aims

The C‐fiber‐mediated bladder‐cooling reflex and the determination of the current perception thresholds (CPTs) permit to investigate afferent LUT pathways. They have both been proposed to detect and differentiate neurologic bladder dysfunction. This study evaluates, prospectively, the effect of oxybutynin, an antimuscarinic with direct antispasmodic effect on smooth muscle, on repeated ice water test (IWT) and CPTs in patients with a known incomplete neurogenic bladder.

Methods

Patients with a known incomplete lesion of the bladder innervation, detrusor overactivity during cystometric bladder filling and a continuous positive response to repeated IWT were included. After the initial tests, 30 mg intravesical oxybutynin (1 mg/ml) was instilled and left in the bladder for 15 min. Afterwards CPTs and IWT were re‐assessed.

Results

After the drug application, the bladder‐cooling reflex could not be initiated, even after three instillations, in 16/17 patients. The bladder CPT increased from 29.7 ± 11.3 to 39.1 ± 15.7 mA after oxybutynin (P = 0.001). No difference was found in CPT of the left forearm (P = 0.208).

Conclusions

Intravesical oxybutynin blocks the bladder‐cooling reflex and increases but does not block CPT sensation in the bladder in most patients with incomplete neurogenic lesion and detrusor overactivity. These results help explain the clinical effect of intravesical oxybutynin in neurogenic patients. They also indicate that a pharmacological local influence on C‐fiber‐related activity can give different clinical effects. Neurourol. Urodynam. 29:391–394, 2010. © 2009 Wiley‐Liss, Inc.
Chronic pudendal neuromodulation: Expanding available treatment options for refractory urologic symptoms
Authors: Peters Kenneth M. , Killinger Kim A. , Boguslawski Brian M. , Boura Judith A.
Published: September 2009

Aims

Chronic pudendal nerve stimulation (CPNS) is a logical alternative particularly in those who fail sacral stimulation. We evaluated symptoms, complications, and satisfaction after CPNS.

Methods

We retrospectively reviewed patients having a tined lead placed at the pudendal nerve via the ischial‐rectal approach. Demographics, history, complications, and pre‐implant voiding diary data were collected. In those responding to CPNS, post‐implant symptom changes were measured with the Interstitial Cystitis Symptom and Problem indices (ICSI‐PI) and voiding diaries at 3, 6, and 12 months, and a mailed survey.

Results

The majority of 84 patients (78.6% female; age 51.8 ± 16.9 years) had interstitial cystitis/painful bladder syndrome, or overactive bladder. Pudendal response (≥ 50% improvement) occurred in 60/84 (71.4%), however 5 of these chose sacral neuromodulation. Almost all (93.2%) who had previously failed sacral neuromodulation responded to pudendal stimulation. Outcomes were evaluated in 55 continuing on CPNS (median follow up 24.1 months). Seven complications requiring 5 revisions, and 4 other re‐operations occurred. Five were explanted. Over time, significant improvements in frequency (P < 0.0001), voided volume (P < 0.0001), incontinence (P < 0.0001), and urgency (P = 0.0019) occurred. ICSI‐PI scores significantly improved over 12 months (P < 0.0001). Survey responses indicated that most still had a device (35/40; 87.5%) continuously in use (24/29; 82.8%), and overall bladder, pelvic pain, incontinence, urgency, and frequency symptoms had improved.

Conclusions

CPNS is a reasonable alternative in complex patients refractory to other therapies including sacral neuromodulation. Continued research is needed to fully assess long‐term outcomes and identify predictors of success. Neurourol. Urodynam. 29:1267–1271, 2010. © 2009 Wiley‐Liss, Inc.
A contingency approach to nonprofit governance
Authors: Bradshaw Patricia
Published: September 2009

A number of contingency factors may be relevant for effective nonprofit organizations and their boards. Although all boards must fulfill certain critical roles and responsibilities, strategic choices can be made about adopting different governance configurations or patterns. These choices can be meaningfully informed by understanding organizational contingencies such as age, size, structure, and strategy—and, even more important, by external contingencies and environmental dimensions such as degree of stability and complexity. This article extends or layers contingency thinking beyond its traditional focus on an alignment between the external environment and the organization's structure to focus as well on the alignment of the organization's governance configuration with its structure and environment. Structural contingency theory in general, and specifically within nonprofits, is reviewed. Two cases are presented of organizations that used an approach based on contingency theory in an action research process to examine and change their governance configurations. The steps they followed may help other nonprofits adapt their governance structures and practices and fulfill their responsibilities for board assessment and reflection.
“To be a business and to keep our humanity”
Authors: Shaw Sally , Allen Justine B.
Published: September 2009

In recent years, the political nature of nonprofit funding has been well established, with research focusing on increased demands for accountability (Eikenberry and Kluver, 2004), difficulties in selecting accountability measures (Reed, Jones, and Irvine, 2005), and the shift from organizational mission that can occur while trying to adhere to funding requirements (Adcroft and Willis, 2005; Parsons and Broadbridge, 2004). This article examines the dynamics between a funder and the nonprofit organizations it funds within an evolving accountability process. Specifically, we use qualitative methods to examine the negotiations between the funder and the nonprofits. Both sides in the funding relationship face tensions as they attempt to work within the constraints of this specific funding regime while trying to maintain their focus on social justice outcomes.
Explaining race, poverty, and gender disparities in advanced course‐taking
Authors: Conger Dylan , Long Mark C. , Iatarola Patrice
Published: September 2009

We use panel data on Florida high school students to examine race, poverty, and gender disparities in advanced course‐taking. While white students are more likely to take advanced courses than black and Hispanic students, these disparities are eliminated when we condition on observable pre–high school characteristics. In fact, black and Hispanic students are more likely than observably similar white students to take advanced courses. Controlling for students' pre–high school characteristics substantially reduces poverty gaps, modestly reduces Asian–white gaps, and makes little dent in female–male gaps. Black and Hispanic students attend high schools that increase their likelihood of taking advanced courses relative to observably similar white students; this advantage is largely driven by minorities disproportionately attending magnet schools. Finally, recent federal and state efforts aimed at increasing access to advanced courses to poor and minority students appear to have succeeded in raising the share of students who take advanced courses from 2003 to 2006. However, secular trends (or spillovers of the policies to non‐poor, non‐minority students) have spurred faster growth for other students, contributing to widening demographic gaps in these years. © 2009 by the Association for Public Policy Analysis and Management.
Structure–property relationship of octa‐substituted POSS in thermal and mechanical reinforcements of conventional polymers
Authors: Tanaka Kazuo , Adachi Shigehiro , Chujo Yoshiki
Published: September 2009

In this article, we describe the structure–property relationships between the polyoctahedral oligomeric silsesquioxane (POSS) fillers and the thermomechanical properties of the polymer composites using polystyrene, poly(methyl methacrylate), and ethylene‐(vinyl acetate) copolymer. We used eight kinds of octa‐substituted aliphatic and aromatic POSS as a filler, and homogeneous polymer composites were prepared with various concentrations of these POSS fillers. From a series of measurements of thermal and mechanical properties of the polymer composites, it was summarized that the longer alkyl chains and unsaturated bonds at the side chains in POSS are favorable to improve the thermal stability and the elasticity of polymer matrices. It was found that phenyl‐POSS can show superior ability to improve the thermomechanical properties of conventional polymers used in this study. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5690–5697, 2009
Development of reactive phosphonated methacrylates
Authors: Edizer Seda , Sahin Gorkem , Avci Duygu
Published: September 2009

Five novel phosphonated mono‐ and dimethacrylate monomers have been synthesized by two different routes. Monomers 1 and 2 were synthesized by reactions of methacryloyl chloride with diethyl (2‐hydroxyphenyl) phosphonate or tetraethyl (2,5‐dihydroxy‐1,4‐phenylene) bisphosphonate; monomers 3 and 4 by reactions of α‐(chloromethyl)acryloyl chloride (CMAC) first with dimethyl (2‐hydroxyethyl) phosphonate and then with benzoic or formic acids. The reaction of CMAC with two moles of dimethyl (2‐hydroxyethyl) phosphonate gave monomer 5. Thermal homopolymerization of monomers 1, 3, 4, and 5 and copolymerization of monomer 1 with methyl methacrylate (MMA) were investigated using azobisisobutyronitrile (AIBN) at 60 °C. Glass transition temperatures were observed for poly‐1, poly(MMA‐co‐1) (50:50), poly(MMA‐co‐1) (90:10), PMMA, poly‐3, and poly‐5 at 52, 90, 99, 129, 50, and 70 °C, respectively. TGA analysis of these polymers indicated formation of char on combustion. Homo‐ and/or copolymerization behavior of the synthesized monomers with 2,2‐bis[4‐(2‐hydroxy‐3‐methacryloyloxy propyloxy) phenyl] propane (Bis‐GMA) were investigated with photodifferential scanning calorimetry. The maximum rate of polymerizations decreased in the following order: Bis‐GMA∼3 > 1 > 4 > 5. The conversions of monomers 1, 3, 4, and 5 (73.9, 85.9, 98.2, and 62.2%) were very high compared with Bis‐GMA (40.5%). © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5737–5746, 2009
Induction of bicalutamide sensitivity in prostate cancer cells by an epigenetic Purα‐mediated decrease in androgen receptor levels
Authors: Liu XiaoMei , Gomez‐Pinillos Alejandro , Liu XiaoJun , Johnson Edward M. , Ferrari Anna C.
Published: September 2009

BACKGROUND

Increased androgen receptor (AR) levels support resistance to apoptosis and hormone therapy in advanced prostate cancer (PC). We recently linked the overexpression of AR in androgen‐independent LNCaP cells (AI‐cells) and tissues from castration‐resistant patients to decreased nuclear levels of Pur‐alpha (Purα) and loss from a protein complex bound to repressor sequences (ARS) in the 5′‐UTR ofAR. Strategies to regain control of increased AR transcription may overcome resistance of AI‐cells and improve treatment outcomes.

METHODS

MTT, real‐time PCR, Western blot, ChIP, flow cytometry, and caspase 3/7 activation measured the effect on growth and targets of LBH589/bicalutamide treatment of AI‐cells and androgen‐dependent LNCaP cells (AD).

RESULTS

Within 16 hr of treatment of AI‐cells with low concentrations of the histone deacetylase inhibitor LBH589, a shift of cytoplasmic Purα restored the nuclear levels and the binding of Purα to the ARS. This was followed by a decline in AR‐mRNA and protein reaching levels of parental AD‐cells. The fraction of AI‐cells in G1 increased and the cells in S phase decreased similar to AD‐cells, and there was a modest caspase activation. Most notably, treatment of bicalutamide‐resistant AI‐cells with 10 nM LBH589 combined with 12.5 µM bicalutamide synergistically inhibited cell growth and induced a fivefold higher level of caspase 3/7 activation than observed in AD‐cells.

CONCLUSIONS

Low‐dose LBH589 restores Purα binding to ARS and down‐regulates AR transcription. Biologically, LBH589 reverses the resistance of AI‐cells to bicalutamide and to apoptosis. The combination may restore the hormonal response of castration‐resistant PC patients. Prostate 70: 179–189, 2010. ©2009 Wiley‐Liss, Inc.
Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV‐1 protease
Authors: Ishima Rieko , Gong Qingguo , Tie Yunfeng , Weber Irene T. , Louis John M.
Published: September 2009

The structural and functional role of conserved residue G86 in HIV‐1 protease (PR) was investigated by NMR and crystallographic analyses of substitution mutations of glycine to alanine and serine (PRG86A and PRG86S). While PRG86S had undetectable catalytic activity, PRG86A exhibited ∼6000‐fold lower catalytic activity than PR. 1H‐15N NMR correlation spectra revealed that PRG86A and PRG86S are dimeric, exhibiting dimer dissociation constants (Kd) of ∼0.5 and ∼3.2 μM, respectively, which are significantly lower than that seen for PR with R87K mutation (Kd > 1 mM). Thus, the G86 mutants, despite being partially dimeric under the assay conditions, are defective in catalyzing substrate hydrolysis. NMR spectra revealed no changes in the chemical shifts even in the presence of excess substrate, indicating very poor binding of the substrate. Both NMR chemical shift data and crystal structures of PRG86A and PRG86S in the presence of active‐site inhibitors indicated high structural similarity to previously described PR/inhibitor complexes, except for specific perturbations within the active site loop and around the mutation site. The crystal structures in the presence of the inhibitor showed that the region around residue 86 was connected to the active site by a conserved network of hydrogen bonds, and the two regions moved further apart in the mutants. Overall, in contrast to the role of R87 in contributing significantly to the dimer stability of PR, G86 is likely to play an important role in maintaining the correct geometry of the active site loop in the PR dimer for substrate binding and hydrolysis. Proteins 2010. © 2009 Wiley‐Liss, Inc.
Receptor assay guided structure‐activity studies of helicokinin insect neuropeptides and peptidomimetic analogues
Authors: Scherkenbeck Jürgen , Antonicek Horst‐Peter , Vogelsang Kathrin , Zdobinsky Tino , Brücher Karin , Rehländer Denise , Chen Heru
Published: September 2009

Neuropeptides control numerous physiological processes in insects. The regulation of water balance is a crucial aspect of homeostasis in terrestrial insects and has been shown to be under endocrine control, primarily by corticotrophin releasing factor (CRF)‐related peptides and kinins. For helicokinin I, a diuretic neuropeptide from the economically important insect pest Heliothis virescens, detailed structure‐activity relationships have been established based on truncated structures, diverse amino acid scans and peptidomimetic analogues. The activities of selected compounds on functional expressed helicokinin receptors are compared with the results of a Malphigian tubule assay. Implications for further peptidomimetic variations are provided. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.