bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Time Delay after Necropsy on Analysis of Simian Varicella-Zoster Virus Expression in Latently Infected Ganglia of Rhesus Macaques
Authors: Mahalingam Ravi , Traina-Dorge Vicki , Wellish Mary , Deharo Eileen , Golive Anjani , Messaoudi Ilhem , Gilden Don
Published: September 2010

Studies of varicella-zoster virus gene expression during latency require the acquisition of human ganglia at autopsy. Concerns have been raised that the virus might reactivate immediately after death. Because features of varicella-zoster virus latency are similar in primate and human ganglia, we examined virus gene expression in tissues either processed immediately or kept at 4°C for 30 h before necropsy of two monkeys inoculated with simian varicella-zoster virus and euthanized 117 days later. Virus transcription and the detection of open reading frame (ORF) 63 protein in the cytoplasm of neurons were comparable. Thus, a 30-h delay after death did not affect varicella-zoster virus expression in latently infected ganglia.
Utilisation of Acupuncture at An Academic Medical Centre
Authors: Vincent Ann , Kruk Kelly M , Cha Stephen S , Bauer Brent A , Martin David P
Published: September 2010

Objective

To provide information about the clinical use of acupuncture at an academic medical centre in the USA.

Methods

A retrospective review of 904 patients (receiving 6070 treatments) who were referred for acupuncture treatment at the Mayo Clinic (Rochester, Minnesota, USA) between 1 January 2004 and 31 December 2008. Data gathered included age, sex, primary diagnosis, number of treatments per diagnosis and health insurance carrier.

Results

The mean (SD) age of the patients was 53.4 (16.2) years; 73.8% were female and 26.2% were male. The three most common diagnostic categories for which acupuncture was used were spinal pain (33.4%), pain (other) (25.1%) and joint pain (12.3%). About 42% of visits were not covered by health insurance carriers and hence patients had to pay themselves. For the remaining 58% of visits, health insurance carriers picked up all or part of the cost of the acupuncture treatments.

Conclusion

The results indicate that pain is the most common reason for use of acupuncture in an academic medical centre and that women use acupuncture more than men. This is one of the few reports of clinical use of acupuncture at academic medical centres in the USA.
IBD patient panels: a personal reflection on three stages of development of an IBD Patient Involvement Project, initiated and supported by Crohn's and Colitis UK
Authors: Canham Peter
Published: September 2010

Crohn's and Colitis UK (formerly The National Association for Colitis and Crohn's Disease) first established a pilot of six inflammatory bowel disease (IBD) patient panels in 2005. There are now 20. Crohn's and Colitis UK offers a framework within which panels can function although there is built in flexibility to suit local circumstances. Patient panels are most effective when they work in partnership with their local NHS professionals. Their uniqueness in the patient and public involvement field lies in their being a disease specific patient group with a focus on their own local IBD services. Panel members are able to speak with the authority of personal experience and with the benefit of assimilated knowledge. A patient panel influences patient care by: (1) providing feedback on current service provision; (2) being a sounding board for departmental developments; (3) initiating suggestions for future developments; and (4) giving support to proposals for departmental developments (perhaps by using the IBD Standards as a benchmark). Most IBD patient panels are self supporting. Some receive assistance from their IBD department. Nationally, Crohn's and Colitis UK provides support through their patient involvement adviser and a patient panel page on their website. Some training and networking is also offered. From the appointment of IBD nurses to changing the way local services are delivered, they have been instrumental in bringing about improvements to IBD services across the country.
Cardiac ischaemia and rhythm disturbances during elective colonoscopy
Authors: George A T , Davis C , Rangaraj A , Edwards C , Chamary V L , Khan H , Javed M , Campbell P G , Allison M C , Swarnkar K J
Published: September 2010

Background

The number of colonoscopic procedures continues to rise rapidly. With widespread adoption of colonoscopy based bowel screening programmes, this rising trend is set to continue.

Aims

This study aimed to identify whether elective colonoscopy could provoke cardiac rhythm disturbances and/or myocardial ischaemia, as evidenced by 12 lead Holter ECG recordings and troponin I (cTnI) changes.

Materials and methods

Patients were stratified into three groups based on the presence of cardiac disease or cardiovascular risk factors. They underwent real time 12 lead Holter monitoring before, during and after colonoscopy. Bloods were taken for pre- and post-procedure cTnI estimation.

Results

Holter ECG recordings of the three groups showed a high incidence of new but silent ischaemic and arrhythmic ECG changes during the colonoscopy in patients with documented but stable heart disease and to a lesser extent in those patients with one or more risk factors for heart disease. Three patients had high cTnI concentrations both before and after colonoscopy. Two patients with known heart disease died within 30 days of colonoscopy.

Conclusions

This study demonstrates for the first time the occurrence of potentially clinically significant ST-T wave changes and rhythm disturbances during elective colonoscopy in patients with known heart disease and to a lesser extent in those patients with a known cardiovascular risk profile.
Association between economic growth and injury mortality among seniors in Colombia
Authors: Trujillo Antonio J , Hyder Adnan A , Ruiz Fernando
Published: September 2010

Background

Injuries among seniors are recognised as an important public health problem not only in developed countries but also in middle-income countries. There is ample epidemiological literature that relates economic growth to the reduction of infectious and childhood diseases. Less evidence exists to document if economic growth alone is enough to reverse the increasing trends of injury mortality and morbidity among seniors in a middle-income country.

Aim

To investigate the association between economic growth and injury deaths among older people in Colombia.

Method

Using data from Colombia, 1979–2006 (n=28), time-series models were used to ascertain if the variation over time in injury mortality among seniors is related to short-term oscillations in economic performance. Four empirical specifications usually used in the analysis of such data were implemented. Models were run by type of injury and gender.

Results

A negative but moderate effect of economic growth was found on injury deaths among older people. The reported elasticity was between −0.98 and −1.26. Men benefit from economic growth more than women. Economic growth seems to reduce traffic injuries, suicides and homicides. A positive association was also found between falls and growth in gross domestic product.

Conclusions

The results indicate a non-homogeneous association between economic growth and injury deaths among seniors in Colombia. This association is usually stronger in a negative direction among children and younger adults. Although more research is needed to understand the causal relationship between economic growth and injury, the association found may suggest that economic growth may not be sufficient to reverse injury deaths among older people; therefore, additional health policies need to be in place to reduce mortality due to preventable injuries in seniors.
Clinicopathological significance of angiopoietin-like protein 4 expression in oesophageal squamous cell carcinoma
Authors: Shibata Kenichiro , Nakayama Toshiyuki , Hirakawa Hiroshi , Hidaka Shigekazu , Nagayasu Takeshi
Published: September 2010

Background

Angiopoietin-like protein 4 (ANGPTL4) is involved in regulating glucose homeostasis, insulin sensitivity, angiogenesis and lipid metabolism, and also acts as an apoptosis survival factor for vascular endothelial cells. The protein is also known to be induced in hypoxic environments characteristic of cancer tissue. Recently, ANGPTL4 was shown in cancer cells to facilitate the transendothelial passage of the cells, resulting in distant metastasis. Clinically, venous invasion resulting in distant metastasis is crucial for oesophageal cancer progression.

Aims

To determine ANGPTL4 expression and its association with clinicopathological factors and prognosis in human oesophageal squamous cell carcinoma (OSCC).

Methods

104 cases of surgically-resected OSCC specimens were examined by immunohistochemistry. The association of ANGPTL4 expression with clinicopathological characteristics and postoperative survival rate was statistically analysed.

Results

Expression of ANGPTL4 was statistically correlated with the degree of differentiation, lymphatic invasion and venous invasion. Results of multivariate analysis, performed using multiple logistic regression, showed that lymph node metastasis, lymphatic invasion and ANGPTL4 expression were independent factors predicting venous invasion. Survival rates of patients with ANGPTL4-positive tumours tended to be statistically lower than those with ANGPTL4-negative tumours.

Conclusions

ANGPTL4 may play an important role in metastasis through lymphovascular invasion, and may potentially affect prognosis.
Temporal changes of under-reporting of cigarette consumption in population-based studies
Authors: Gallus Silvano , Tramacere Irene , Boffetta Paolo , Fernandez Esteve , Rossi Silvia , Zuccaro Piergiorgio , Colombo Paolo , La Vecchia Carlo
Published: September 2010

Objectives

To monitor trends in under-reporting of smoking in Italy over the last two decades.

Methods

A total of 9 representative population-based surveys on smoking conducted in Italy in 1990 and annually between 2001 and 2008, covering 26 397 individuals, were studied. The number of cigarettes per day per person aged 15 years or over, obtained from these interview-based surveys, was compared with official data from legal sales.

Results

Over the last two decades, self-reported smoking prevalence progressively decreased from 32% in 1990 to 22% in 2008. Self-reported daily per capita consumption of cigarettes also showed a reduction between 1990 and 2008, notably so over the last few years (from 5.2 in 1990 to 4.0 in 2004 to 3.2 in 2008). According to data from legal sales, number of cigarettes per day per person decreased from 5.3 in 1990 to 5.0 in 1992, levelled off from 1992 to 1997, subsequently increased from 5.0 in 1997 to 5.8 in 2002 (likely due to control of smuggling), and decreased over the last 6 years (to 4.9 in 2008). These figures correspond to an under-reporting of approximately 1% in 1990, 25% in 2001 and up to 35% in 2008.

Conclusions

The difference in cigarette consumption between legal sale and self-reported data has substantially increased over the last two decades in Italy, reflecting increasing under-reporting of cigarette consumption mainly due to a decreasing social acceptability of smoking. Comparisons between interview-based and legal sale data are complicated by factors such as smuggling control and changes in the population (eg, increased proportion of immigrants); however these are able to justify only a small proportion of the gap found in Italy.
The Anthropology of Credit and Debt
Authors: Peebles Gustav
Published: September 2010

Whether concerned with kinship or with kula, anthropology's interest in credit and debt goes back to the very beginnings of the discipline. Nevertheless, this review dedicates itself primarily to more recent research trends into credit and debt's powerful nature and effects. Following Mauss, credit and debt are treated as an indissoluble dyad that contributes to diverse regulatory mechanisms of sociality, time, space, and the body. Anthropology's overarching contribution to this field of inquiry rotates around its refusal to segregate the moral from the material, seeing the ubiquitous moral debates surrounding credit and debt in various ethnographic settings as coconstitutive of their material effects.
Anthropologies of the United States
Authors: Cattelino Jessica R.
Published: September 2010

This article reviews recent research in sociocultural anthropology that has been conducted in and about the United States. I show that anthropologists of the United States have been concerned to locate the anthropological field in three ways: spatial investigations of region, community, and territory; epistemological and methodological projects of cultural critique and defamiliarization; and reconsideration of the place of Native North America in the anthropology of the United States. Emergent inquiry into settler colonialism and the politics of indigeneity has the potential to strengthen the anthropology of the United States by accounting for the ways that being a settler society structures all American lives.
Enactments of Expertise
Authors: Carr E. Summerson
Published: September 2010

Every society recognizes expertise, and anthropologists have long documented the culturally and historically specific practices that constitute it. The anthropology of expertise focuses on what people do rather than what people possess, even in the many circumstances where the former is naturalized as the latter. Across its many domains, expertise is both inherently interactional, involving the participation of objects, producers, and consumers of knowledge, and inescapably ideological, implicated in the evolving hierarchies of value that legitimate particular ways of knowing as “expert.” This review focuses on the semiotics of expertise, highlighting four constitutive processes: socialization practices through which people establish intimacy with classes of cultural objects and learn to communicate that familiarity; evaluation, or the establishment of asymmetries among people and between people and objects; institutionalization, wherein ways of knowing are organized and authorized; and naturalization, or the essentialization of expert enactments as bodies of knowledge.
Education, Religion, and Anthropology in Africa
Authors: Stambach Amy
Published: September 2010

Taking as its starting point classic accounts of native education and culture contact, this article reviews key trends and orientations that have shaped the anthropological study of education and religion in Africa. It identifies three frames that capture the development of research chronologically from the 1930s onward: (a) a functionalist focus on Christian-inflected adaptive education; (b) applied and sociohistorical emphases on education as, respectively, an engine for driving secular change and a medium through which to shape new ritualized practices and religious beliefs; and (c) a more recent concentration on youth education as a key site for analyzing politicized religious identity and youths' radicalization. I argue that this trajectory of research foregrounds two phenomena that anthropology also underanalyzes: first, the close association of religious missions with the development of today's highly secularized yet religiously inflected regional and global institutions that support educational programming in Africa; and second, a marginalization of the study of Islam in Africa, which reflects a Christianized cultural legacy in anthropological studies of religion and education.
Sensory Impairment
Authors: Keating Elizabeth , Hadder R. Neill
Published: September 2010

Anthropological studies of sensory impairment address biological conditions and cultural disablement while contributing to theoretical discussions of cultural competence, communicative practices, the role of narrative, and features of identity, ideologies, and technology. As boundary cases, impairments can disclose essential aspects of the senses in human life. Sensory impairment studies navigate the complexities of comparing dominant sensory discourses with individual sense differences, cross-linguistic incomparabilities among sense categories, and how impairment categories tend to fuse together highly diverse conditions. The category of disability, which includes sensory impairment, comprises chronic deficit relative to priority competencies. With special emphasis on blindness/visual impairment and deafness/hearing impairment, we overview sensory impairment on three levels: the social partitioning of the sensorium, differential ramifications of sensory impairments cross-culturally, and the classification of the person based on cultural priorities. We identify ten common themes in ethnographically oriented studies.
Property and Persons: New Forms and Contests in the Era of Neoliberalism
Authors: Hirsch Eric
Published: September 2010

The past few decades have witnessed an eruption of property claims worldwide. The new form of cultural property has emerged. There has also been a marked growth in claims of intellectual property that are now applied to an expanded array of things and contexts. Older property forms, such as landownership, are deployed in new contexts, generating novel contests about the capacity of land to be exclusively owned. The ideology of neoliberalism and new technologies of biology, information, and communication are central to these transformations in property relations. In their distinctive ways, each has contributed to the expansion of property claims while continually disrupting the division of persons and things central to property. The article considers how contests about new and old property forms are simultaneously generative of new forms of persons, such as indigenous persons, whose outlook and conduct potentially undermine the legitimacy of conventional property claims.
The Reorganization of the Sensory World
Authors: Porcello Thomas , Meintjes Louise , Ochoa Ana Maria , Samuels David W.
Published: September 2010

Although anthropological and critical social theory have a long interest in sensory experience, work on the senses has intensified within the past 20 years. This article traces three sensory genealogies within anthropology: the work of Ong and McLuhan as critiqued and advanced by David Howes and the Concordia Project; phenomenological studies as advanced by Paul Stoller; and a focus on materialities as advanced by Nadia Seremetakis. Studies of individual senses, which we survey, led to calls for a more integrated approach to the senses, both within anthropology and from cinema and media studies. In various ways, the senses are constituted by their imbrication in mediated cultural practices, whether mediated by technology, discourse, or local epistemologies. We argue that integrating language and discourse into the study of the senses along with new media insights more fully articulates the significance of body-sensorial knowledge.
Consanguineous Marriage and Human Evolution
Authors: Bittles A.H. , Black M.L.
Published: September 2010

Mate choice among early human groups and in many historical populations was subject to both demographic and social constraints, ensuring that most unions were between couples who had coinherited substantial proportions of their genomes from common ancestors. Even in populations in which close consanguineous marriage was proscribed, community endogamy would have been sufficient to ensure high levels of homozygosity. Consanguineous marriage remains the choice of an estimated 10.4% of the global population, although there has been an overall decline in its popularity, especially in developed countries. Recent studies have indicated that the shift from consanguineous marriage to panmixia has been accompanied by a reduction in homozygosity. The concomitant predicted decrease in incidence of both recessive single-gene disorders and more common adult-onset diseases will have a significant impact on the health of future generations.
Anthropological Perspectives on Structural Adjustment and Public Health
Authors: Pfeiffer James , Chapman Rachel
Published: September 2010

Thirty years since its first public use in 1980, the phrase structural adjustment remains obscure for many anthropologists and public health workers. However, structural adjustment programs (SAPs) are the practical tools used by international financial institutions (IFIs) such as the International Monetary Fund (IMF) and the World Bank to promote the market fundamentalism that constitutes the core of neoliberalism. A robust debate continues on the impact of SAPs on national economies and public health. But the stories that anthropologists tell from the field overwhelmingly speak to a new intensity of immiseration produced by adjustment programs that have undermined public sector services for the poor. This review provides a brief history of structural adjustment, and then presents anthropological analyses of adjustment and public health. The first section reviews studies of health services and the second section examines literature that assesses broader social determinants of health influenced by adjustment.
Archaeology of the Eurasian Steppes and Mongolia
Authors: Hanks Bryan
Published: September 2010

International interest in the prehistory and archaeology of the Eurasian steppes and Mongolia has increased dramatically since the collapse of the Soviet Union in 1991. This article surveys important new evidence and interpretations that have emerged from several collaborative projects in the past two decades. A particular emphasis is placed on issues that are crucial to regional studies in the steppe ecological zone; however, it also is suggested that steppe prehistory must come to play a more significant role in developing more comprehensive understandings of world prehistory. Key developments connected with the steppe include the diffusion of anatomically modern humans, horse domestication, spoke-wheeled chariot and cavalry warfare, early metal production and trade, Indo-European languages, and the rise of nomadic states and empires. In addition to these important issues, thoughts are offered on some of the current challenges that face archaeological scholarship in this region of the world.
Identification and functional characterization of malignant hyperthermia mutation T1354S in the outer pore of the Cavα1S-subunit
Authors: Pirone Antonella , Schredelseker Johann , Tuluc Petronel , Gravino Elvira , Fortunato Giuliana , Flucher Bernhard E. , Carsana Antonella , Salvatore Francesco , Grabner Manfred
Published: September 2010

To identify the genetic locus responsible for malignant hyperthermia susceptibility (MHS) in an Italian family, we performed linkage analysis to recognized MHS loci. All MHS individuals showed cosegregation of informative markers close to the voltage-dependent Ca2+channel (CaV) α1S-subunit gene (CACNA1S) with logarithm of odds (LOD)-score values that matched or approached the maximal possible value for this family. This is particularly interesting, because so far MHS was mapped to >178 different positions on the ryanodine receptor (RYR1) gene but only to two on CACNA1S. Sequence analysis of CACNA1S revealed a c.4060A>T transversion resulting in amino acid exchange T1354S in the IVS5-S6 extracellular pore-loop region of CaVα1Sin all MHS subjects of the family but not in 268 control subjects. To investigate the impact of mutation T1354S on the assembly and function of the excitation-contraction coupling apparatus, we expressed GFP-tagged α1ST1354S in dysgenic (α1S-null) myotubes. Whole cell patch-clamp analysis revealed that α1ST1354S produced significantly faster activation of L-type Ca2+currents upon 200-ms depolarizing test pulses compared with wild-type GFP-α1S(α1SWT). In addition, α1ST1354S-expressing myotubes showed a tendency to increased sensitivity for caffeine-induced Ca2+release and to larger action-potential-induced intracellular Ca2+transients under low (≤2 mM) caffeine concentrations compared with α1SWT. Thus our data suggest that an additional influx of Ca2+due to faster activation of the α1ST1354S L-type Ca2+current, in concert with higher caffeine sensitivity of Ca2+release, leads to elevated muscle contraction under pharmacological trigger, which might be sufficient to explain the MHS phenotype.
Hypoxic upregulation of arginase II in human lung endothelial cells
Authors: Krotova Karina , Patel Jawaharlal M. , Block Edward R. , Zharikov Sergey
Published: September 2010

Activated arginase has been implicated in many diseases including cancer, immune cell dysfunction, infections, and vascular disease. Enhanced arginase activity has been reported in lungs of patients with pulmonary artery hypertension. We used hypoxia as a model for pulmonary hypertension and studied the effect of exposure to hypoxia on arginase activity in human lung microvascular endothelial cells (HMVEC). Hypoxia induces upregulation of arginase activity as well as mRNA and protein levels of arginase II (Arg II), the only arginase isoform we were able to identify in HMVEC. In endothelial cells, arginase shares and competes for the substrate l-arginine with nitric oxide (NO) synthase (NOS). Through regulation of substrate availability for NOS, arginase is able to modulate NO production. To evaluate the role of Arg II in regulation of NO production under hypoxia, we compared NO output (RFL-6 reporter assay) in cells with normal and silenced Arg II. Exposure to hypoxia led to an increase in NO levels produced by HMVEC. Inhibition of Arg II by specific small interfering RNA or by the pharmacological inhibitor BEC additionally enhanced the levels of NO. Another possible role for activated arginase is involvement in regulation of cell proliferation. However, we showed that hypoxia decreased cell proliferation and upregulated Arg II did not have an effect on cell proliferation. Since hypoxia-inducible factors (HIF) are a family of transcriptional factors activated by hypoxia, we tested the possibility of involvement of HIF-1 and HIF-2 in regulation of Arg II under hypoxia. The silencing of HIF-2 but not HIF-1 prevented the activation of Arg II by hypoxia.
The intrinsic electrophysiological properties of neurons derived from mouse embryonic stem cells overexpressing neurogenin-1
Authors: Tong Mingjie , Hernandez Jeannie L. , Purcell Erin K. , Altschuler Richard A. , Duncan R. Keith
Published: September 2010

A mouse embryonic stem (ES) cell line containing an inducible transgene for the proneural gene Neurog1 has been used to generate glutamatergic neurons at a high efficiency. The present study used in vitro electrophysiology to establish the timeline for acquiring a functional neuronal phenotype in Neurog1-induced cells exhibiting a neuronal morphology. TTX-sensitive action potentials could be evoked from over 80% of the cells after only 4.5 days in vitro (DIV). These cells uniformly showed rapidly adapting responses to current injection, firing one to three action potentials at the onset of the stimulus. In the absence of Neurog1, a limited number of ES cells adopted a neuronal morphology, but these cells displayed slow calcium depolarizations rather than sodium-based spikes. Voltage-gated Na+, K+, and Ca2+ currents were present in nearly all induced cells as early as 4.5 DIV. The voltage-dependent properties of these currents changed little from 4 to 12 DIV with half-activation voltage varying by <10 mV for any current type throughout the culture period. This study demonstrates that forced expression of proneural genes can induce ES cells to quickly acquire a functional neuronal phenotype with mature electrophysiological properties. Transient overexpression of Neurog1 may be used in neural repair strategies that require the rapid induction of functional neurons from pluripotent stem cells.
Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells
Authors: Chacko Simi M. , Ahmed Shabnam , Selvendiran Karuppaiyah , Kuppusamy M. Lakshmi , Khan Mahmood , Kuppusamy Periannan
Published: September 2010

Stem cells transplanted to the ischemic myocardium usually encounter massive cell death within a few days of therapy. Hypoxic preconditioning (HPC) is currently employed as a strategy to prepare stem cells for increased survival and engraftment in the heart. However, HPC of stem cells has provided varying results, supposedly due to the differences in the oxygen concentration, duration of exposure, and passage conditions. In the present study, we determined the effect of HPC on rat mesenchymal stem cells (MSCs) exposed to 0.5% oxygen concentration for 24, 48, or 72 h. We evaluated the expression of prosurvival, proangiogenic, and functional markers such as hypoxia-inducible factor-1α, VEGF, phosphorylated Akt, survivin, p21, cytochrome c, caspase-3, caspase-7, CXCR4, and c-Met. MSCs exposed to 24-h hypoxia showed reduced apoptosis on being subjected to severe hypoxic conditions. They also had significantly higher levels of prosurvival, proangiogenic, and prodifferentiation proteins when compared with longer exposure (72 h). Cells taken directly from the cryopreserved state did not respond effectively to the 24-h HPC as those that were cultured under normoxia before HPC. Cells cultured under normoxia before HPC showed decreased apoptosis, enhanced expression of connexin-43, cardiac myosin heavy chain, and CD31. The preconditioned cells were able to differentiate into the cardiovascular lineage. The results suggest that MSCs cultured under normoxia before 24-h HPC are in a state of optimal expression of prosurvival, proangiogenic, and functional proteins that may increase the survival and engraftment in the infarct heart. These results could provide further insights into optimal preparation of MSCs which would greatly influence the effectiveness of cell therapy in vivo.
Molecular mechanisms underlying Ca2+-mediated motility of human pancreatic duct cells
Authors: Dong Hui , Shim Ki-Nam , Li Jenny M. J. , Estrema Christine , Ornelas Tiffany A. , Nguyen Flang , Liu Shanglei , Ramamoorthy Sonia L. , Ho Samuel , Carethers John M. , Chow Jimmy Y. C.
Published: September 2010

We recently reported that transforming growth factor-β (TGF-β) induces an increase in cytosolic Ca2+ ([Ca2+]cyt) in pancreatic cancer cells, but the mechanisms by which TGF-β mediates [Ca2+]cyt homeostasis in these cells are currently unknown. Transient receptor potential (TRP) channels and Na+/Ca2+ exchangers (NCX) are plasma membrane proteins that play prominent roles in controlling [Ca2+]cyt homeostasis in normal mammalian cells, but little is known regarding their roles in the regulation of [Ca2+]cyt in pancreatic cancer cells and pancreatic cancer development. Expression and function of NCX1 and TRPC1 proteins were characterized in BxPc3 pancreatic cancer cells. TGF-β induced both intracellular Ca2+ release and extracellular Ca2+ entry in these cells; however, 2-aminoethoxydiphenyl borate [2-APB; a blocker for both inositol 1,4,5-trisphosphate (IP3) receptor and TRPC], LaCl3 (a selective TRPC blocker), or KB-R7943 (a selective inhibitor for the Ca2+ entry mode of NCX) markedly inhibited the TGF-β-induced increase in [Ca2+]cyt. 2-APB or KB-R7943 treatment was able to dose-dependently reverse membrane translocation of PKCα induced by TGF-β. Transfection with small interfering RNA (siRNA) against NCX1 almost completely abolished NCX1 expression in BxPc3 cells and also inhibited PKCα serine phosphorylation induced by TGF-β. Knockdown of NCX1 or TRPC1 by specific siRNA transfection reversed TGF-β-induced pancreatic cancer cell motility. Therefore, TGF-β induces Ca2+ entry likely via TRPC1 and NCX1 and raises [Ca2+]cyt in pancreatic cancer cells, which is essential for PKCα activation and subsequent tumor cell invasion. Our data suggest that TRPC1 and NCX1 may be among the potential therapeutic targets for pancreatic cancer.
Role of the organum vasculosum of the lamina terminalis for the chronic cardiovascular effects produced by endogenous and exogenous ANG II in conscious rats
Authors: Vieira Alexandre A. , Nahey David B. , Collister John P.
Published: September 2010

Endogenous and exogenous circulating ANG II acts at one of the central circumventricular organs (CVOs), the subfornical organ (SFO), to modulate chronic blood pressure regulation. However, at the forebrain, another important CVO is the organum vasculosum of the lamina terminalis (OVLT). In the present study, we tested the hypothesis that the OVLT mediates the hypertension or the hypotension produced by chronic infusion of ANG II or losartan (AT1 antagonist), respectively. Six days after sham or OVLT electrolytic lesion, male Sprague-Dawley rats (280–320 g, n = 6 per group) were instrumented with intravenous catheters and radiotelemetric blood pressure transducers. Following another week of recovery, rats were given 3 days of saline control infusion (7 ml/day) and were then infused with ANG II (10 ng·kg−1·min−1) or losartan (10 mg·kg−1·day−1) for 10 days, followed by 3 recovery days. Twenty-four hour average measurements of mean arterial pressure (MAP) and heart rate (HR) were made during this protocol. Hydromineral balance (HB) responses were measured during the experimental protocol. By day 9 of ANG II treatment, MAP had increased 16 ± 4 mmHg in sham rats but only 4 ± 1 mmHg in OVLT lesioned rats without changes in HR or HB. However, the hypotension produced by 10 days of losartan infusion was not modified in OVLT lesioned rats. These results suggest that the OVLT might play an important role during elevation of plasma ANG II, facilitating increases of blood pressure but is not involved with baseline effects of endogenous ANG II.
Deficits in gastrointestinal responses controlling food intake and body weight
Authors: Covasa Mihai
Published: September 2010

The gastrointestinal tract serves as a portal sensing incoming nutrients and relays mechanical and chemosensory signals of a meal to higher brain centers. Prolonged consumption of dietary fat causes adaptive changes within the alimentary, metabolic, and humoral systems that promote a more efficient process for energy metabolism from this rich source, leading to storage of energy in the form of adipose tissue. Furthermore, prolonged ingestion of dietary fats exerts profound effects on responses to signals involved in termination of a meal. This article reviews the effects of ingested fat on gastrointestinal motility, hormone release, and neuronal substrates. It focuses on changes in sensitivity to satiation signals resulting from chronic ingestion of high-fat diet, which may lead to disordered appetite and dysregulation of body weight.
8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: role of cAMP and protein kinase A
Authors: Cabral Pablo D. , Silva Guillermo B. , Baigorria Sandra T. , Juncos Luis A. , Juncos Luis I. , García Néstor H.
Published: September 2010

Salt reabsorption by the loop of Henle controls NaCl handling and blood pressure regulation. Increased oxidative stress stimulates NaCl transport in one specific segment of the loop of Henle called the thick ascending limb (TAL). The isoprostane 8-iso-prostaglandin-F2α (8-iso-PGF2α) is one of the most abundant nonenzymatic lipid oxidation products and has been implicated in the development of hypertension. However, it is not known whether 8-iso-PGF2α regulates transport or the mechanisms involved. Because protein kinase A (PKA) stimulates NaCl transport in several nephron segments, we hypothesized that 8-iso-PGF2α increases NaCl transport in the cortical TAL (cTAL) via a PKA-dependent mechanism. We examined the effect of luminal 8-iso-PGF2α on NaCl transport by measuring chloride absorption ( JCl) in isolated microperfused cTALs. Adding 8-iso-PGF2α to the lumen increased JClby 54% (from 288.7 ± 30.6 to 446.5 ± 44.3 pmol·min−1·mm−1; P < 0.01), while adding it to the bath enhanced JClby 35% (from 236.3 ± 35.3 to 319.2 ± 39.8 pmol·min−1·mm−1; P < 0.05). This stimulation was blocked by Na-K-2Cl cotransporter inhibition. Next, we tested the role of cAMP. Basal cAMP in the cTAL was 18.6 ± 1.6 fmol·min−1·mm−1, and 8-iso-PGF2α raised it to 35.1 ± 1.4 fmol·min−1·mm−1, an increase of 94% ( P < 0.01). Because cAMP stimulates PKA, we measured JClusing the PKA-selective inhibitor H89. In the presence of H89 (10 μM), 8-iso-PGF2α failed to increase transport regardless of whether it was added to the lumen (216.1 ± 16.7 vs. 209.7 ± 23.8 pmol·min−1·mm−1; NS) or the bath (150.4 ± 32.9 vs. 127.1 ± 28.6 pmol·min−1·mm−1; NS). We concluded that 8-iso-PGF2α stimulates cAMP and increases Cl transport in cTALs via a PKA-dependent mechanism.
Natriuretic and antikaliuretic effects of uroguanylin and prouroguanylin in the rat
Authors: Moss Nicholas G. , Riguera Dorothy A. , Fellner Robert C. , Cazzolla Christopher , Goy Michael F.
Published: September 2010

The peptide uroguanylin (Ugn) is stored and released as a propeptide (proUgn) by enterochromaffin cells in the intestine, and converted to Ugn and other metabolites in the renal tubules. Both proUgn and Ugn are natriuretic, although the response to proUgn is thought to depend on its conversion to Ugn within nephrons. To assess the efficiency of intrarenal conversion of proUgn to Ugn, we measured urinary Ugn excretion in rats following intravenous infusions of proUgn or Ugn. Infusion of 2 and 10 nmol proUgn/kg body wt increased plasma proUgn concentration from 2.2 ± 0.3 to 5.6 ± 1.3 pmol/ml and to 37 ± 9.6 pmol/ml, respectively. No proUgn was detected in urine before, during, or after proUgn infusions. These two proUgn infusion doses resulted in total Ugn recovery in urine of 162 ± 64 and 206 ± 39 pmol/kg body wt (9 and 2% of the infused amount, respectively). By contrast, the same molar amounts of Ugn resulted in 1,009 ± 477 and 5,352 ± 2,133 pmol/kg body wt of Ugn in urine (recoveries of ∼50%). Unexpectedly, comparisons of natriuretic dose-response curves for each peptide showed proUgn to be about five times more potent than Ugn, despite the relatively modest amount of Ugn generated from infused proUgn. In addition, both peptides were antikaliuretic at low doses, but in this case Ugn showed greater potency than proUgn. These data do not support Ugn as the primary active principle of proUgn for regulation of renal sodium excretion. Instead, an alternative peptide fragment produced from proUgn may be responsible for natriuretic activity in the kidney, whereas Ugn itself may play an antikaliuretic role.
Mineralocorticoid receptor degradation is promoted by Hsp90 inhibition and the ubiquitin-protein ligase CHIP
Authors: Faresse Nourdine , Ruffieux-Daidie Dorothée , Salamin Mélanie , Gomez-Sanchez Celso E. , Staub Olivier
Published: September 2010

The mineralocorticoid receptor (MR) plays a crucial role in the regulation of Na+balance and blood pressure, as evidenced by gain of function mutations in the MR of hypertensive families. In the kidney, aldosterone binds to the MR, induces its nuclear translocation, and promotes a transcriptional program leading to increased transepithelial Na+transport via the epithelial Na+channel. In the unliganded state, MR is localized in the cytosol and part of a multiprotein complex, including heat shock protein 90 (Hsp90), which keeps it ligand-binding competent. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic that binds to Hsp90 and alters its function. We investigated whether 17-AAG affects the stability and transcriptional activity of MR and consequently Na+reabsorption by renal cells. 17-AAG treatment lead to reduction of MR protein level in epithelial cells in vitro and in vivo, thereby interfering with aldosterone-dependent transcription. Moreover, 17-AAG inhibited aldosterone-induced Na+transport, possibly by interfering with MR availability for the ligand. Finally, we identified the ubiquitin-protein ligase, COOH terminus of Hsp70-interacting protein, as a novel partner of the cytosolic MR, which is responsible for its polyubiquitylation and proteasomal degradation in presence of 17-AAG. In conclusion, 17-AAG may represent a novel pharmacological tool to interfere with Na+reabsorption and hypertension.
Follistatin-like 1 regulates renal IL-1β expression in cisplatin nephrotoxicity
Authors: Adams Derek C. , Karolak Michele J. , Larman Barry W. , Liaw Lucy , Nolin James D. , Oxburgh Leif
Published: September 2010

Follistatin-like 1 (FSTL1) is a secreted protein with homology to both Follistatin and the SPARC/BM40 family of matricellular proteins. In this study, we sought to determine the expression patterns of Fstl1 and its cognate receptor Dip2a in the adult, and to assess the consequences of Fstl1 inactivation on development and homeostasis of the kidney. We find that FSTL1 circulates at high levels in both the human and the mouse and that it is also locally expressed in the loop of Henle in the kidney. To begin to understand the in vivo functions of Fstl1, we generated a mouse mutant using a genetrap approach. The hypomorphic Fstl1 genetrap strain displays a strong reduction in FSTL1 expression at the protein level, but it does not show overt developmental defects. FSTL1 has previously been implicated in diverse disease processes as a regulator of inflammatory cytokine expression, and we therefore evaluated the response of the genetrap strain to cisplatin-mediated acute kidney injury, a disease model with highly cytokine-dependent pathology. We find that although TNF-α and Il6 levels are unchanged relative to wild-type, renal Il-1β expression is increased in genetrap mice following cisplatin treatment. Furthermore, histopatological analysis, expression of the tissue injury marker Havcr1, and measurement of serum creatinine demonstrate that reduction of Fstl1 expression sensitizes the kidney to acute cisplatin nephrotoxicity, suggesting a role for FSTL1-mediated Il-1β suppression in protection of the kidney from acute nephrotoxic injury.
Neuropilin-VEGF signaling pathway acts as a key modulator of vascular, lymphatic, and inflammatory cell responses of the bladder to intravesical BCG treatment
Authors: Saban Marcia R. , Sferra Thomas J. , Davis Carole A. , Simpson Cindy , Allen Arielle , Maier Julie , Fowler Ben , Knowlton Nicholas , Birder Lori , Wu Xue-Ru , Saban Ricardo
Published: September 2010

Recent findings indicate that VEGF receptors and coreceptors (neuropilins; NRP) are expressed on nonendothelial cells in human bladder urothelium, in one human bladder cancer cell line (J82), and in the mouse bladder urothelium. In addition, VEGFR1, VEGFR2, NRP1, and NRP2 expressions were upregulated in animal models of chronic bladder inflammation induced by four weekly instillations of protease-activated receptors (PAR)-activating peptides or bacillus Calmette-Guérin (BCG) into the mouse bladder. Here, we used four weekly instillations of BCG as a model for chronic bladder inflammation to further investigate whether VEGF receptors and NRPs play a role in the migration of inflammatory cells and inflammation-induced lymphangiogenesis and angiogenesis. For this purpose, we used neutralizing antibodies that were engineered to specifically block the binding of VEGF to NRP (anti-NRP1B) and the binding of semaphorins to NRP (anti-NRP1A). C57BL/6 mice received intraperitoneal injections of PBS, anti-NRP1A- or anti-NRP1B-neutralizing antibodies and then were challenged chronically with intravesical PBS or BCG. At the end of chronic challenge period, a fluorescent internalizable tracer, scVEGF/Cy5.5, was administered to all mice and near-infrared fluorescence images were obtained in vivo and in real time. BCG increased the overall accumulation of scVEGF/Cy5.5 in the urinary bladder urothelium and inflammatory cells. In addition, BCG increased the density of blood and lymphatic vessels concomitantly with an upregulation of NRP2 expression in lymphatic vessels. Treatment of the mice with NRP1-neutralizing antibodies dramatically reduced scVEGF/Cy5.5 uptake, polymorphonuclear (myeloperoxidase-positive cells) and dendritic cell (CD11c-positive cells) infiltration, and decreased the overall density of BCG-induced blood and lymphatic vessels. These results implicate NRPs as critical in vivo regulators of the vascular and inflammatory responses to the intravesical administration of BCG.
INK4a knockout mice exhibit increased fibrosis under normal conditions and in response to unilateral ureteral obstruction
Authors: Wolstein Jesse M. , Lee David H. , Michaud Jennine , Buot Venessa , Stefanchik Beth , Plotkin Matthew D.
Published: September 2010

The INK4a proteins p16INK4a and p19ARF regulate cell cycle arrest and senescence. However, the role of these proteins in controlling these processes in the normal kidney and following injury is unknown. We performed unilateral ureteral obstruction (UUO) to induce fibrosis in 2- to 3-mo-old wild-type (WT) C57/B6 and INK4a knockout mice. By quantitative RT-PCR, p16INK4a levels were increased sixfold in WT mice 7 days after UUO and p19ARF remained undetectable. Kidney sections were examined to determine levels and localization of p16INK4a, apoptosis, fibrosis, and senescent cells. INK4a knockout mice displayed mesangial cell proliferation, increased matrix deposition, and myofibroblast differentiation under normal conditions. Following UUO, INK4a knockout mice displayed 10-fold increased tubular and interstitial cell proliferation, 75% decreased collecting duct apoptosis, 2-fold greater collagen and fibronectin deposition, and no cell senescence by senescence-associated β-galactosidase staining compared with WT mice. Both INK4a knockout mesangial cells and kidney lysates from knockout mice following injury showed elevated levels of IL-6 by ELISA compared with WT samples. INK4a knockout epithelial cell cultures displayed increased mesenchymal cell markers when exposed to transforming growth factor-β. These results confirm that p16INK4a controls cell proliferation and matrix production and mitigates fibrosis following injury and suggest that the mechanism involves a role in limiting inflammation and cell proliferation.
P2X7receptors mediate deleterious renal epithelial-fibroblast cross talk
Authors: Ponnusamy Murugavel , Ma Li , Gong Rujun , Pang Maoyin , Chin Y. Eugene , Zhuang Shougang
Published: September 2010

Peritubular fibroblasts in the kidney are the major erythropoietin-producing cells and also contribute to renal repair following acute kidney injury (AKI). Although few fibroblasts were observed in the interstitium adjacent to damaged tubular epithelium in the early phase of AKI, the underlying mechanism by which their numbers were reduced remains unknown. In this study, we tested the hypothesis that damaged renal epithelial cells directly induce renal interstitial fibroblast death by releasing intracellular ATP and activating purinergic signaling. Exposure of a cultured rat renal interstitial fibroblast cell line (NRK-49F) to necrotic renal proximal tubular cells (RPTC) lysate or supernatant induced NRK-49F cell death by apoptosis and necrosis. Depletion of ATP with apyrase or inhibition of the P2X purinergic receptor with pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid blocked the deleterious effect of necrotic RPTC supernatant. The P2X7receptor, an ATP-sensitive purinergic receptor, was not detected in cultured NRK-49F cells but was inducible by necrotic RPTC supernatant. Treatment with A438079, a highly selective P2X7receptor inhibitor, or knockdown of the P2X7receptor with small interference RNA diminished renal fibroblast death induced by necrotic RPTC supernatant. Conversely, overexpression of the P2X7receptor potentiated this response. Collectively, these findings provide strong evidence that damaged renal epithelial cells can directly induce the death of renal interstitial fibroblasts by ATP activation of the P2X7receptor.