bluuebunny/crossref_metadata_2025 huggingface dataset:
Marathon Running as a Cause of Troponin Elevation: A Systematic Review and Meta‐Analysis
Authors: REGWAN STEVEN , HULTEN EDWARD A. , MARTINHO SHAUN , SLIM JENNIFER , VILLINES TODD C. , MITCHELL JOSHUA , SLIM AHMAD M.
Published: July 2010

Background:
 Cardiac troponin (cTn) has high sensitivity and specificity for myocardial injury in acute coronary syndrome. Our objective was to review the published literature regarding the incidence of cTn elevations in marathon runners.

Methods:
 Systematic review and meta‐analysis of observational studies published before September 2009. We included studies of patients who had completed a marathon and had serum cTn levels within 24 hours. The primary outcome was the odds ratio for conversion of a normal pre‐marathon cTn to an elevated post‐marathon cTn. Secondary outcomes included the pooled prevalence of cTn elevation and comparison of the odds ratio for post‐marathon elevation of cTnI versus cTnT.

Results:
 Sixteen studies of 939 participants met criteria for inclusion. The mean age was 39 ± 4 years and patients were 74 ± 14% male. There were 6 pre‐marathon cTn elevations and 579 post‐race elevations. The pooled odds ratio for converting from a normal pre‐race to an elevated post‐race cTn was 51.84 (95% CI 16–168, I2= 66%, P < 0.001). The pooled incidence of a post‐marathon cTn elevation was 51% (95% CI 33–69, I2= 98%, P < 0.001) of all runners. For the primary outcome there was no significant publication bias. Age and gender were not associated, but publication date and assay sensitivity was associated with cTn elevation. cTnI was less commonly elevated versus cTnT.

Conclusions:
 The available data demonstrate that cTn levels are frequently elevated after a marathon with unclear cardiovascular significance. This elevation of cTn appears to be consistent among a diverse patient population. (J Interven Cardiol 2010;23:443–450)
Immunoprofiling of patients with chronic myeloid leukemia at diagnosis and during tyrosine kinase inhibitor therapy
Authors: Rohon Peter , Porkka Kimmo , Mustjoki Satu
Published: July 2010

Tyrosine kinase inhibitors (TKIs) are the current standard treatment in chronic myeloid leukemia (CML). In addition to the BCR‐ABL target oncoprotein, they also inhibit off‐target kinases (e.g. c‐KIT, TEC, SRC), some of which have physiological functions in immune responses. In vitro studies have implied immunosuppressive effects of TKI treatment. As comprehensive in vivo data are missing, we aimed at analyzing the detailed immunoprofile of patients with CML at diagnosis and during therapy. We collected 88 peripheral blood (PB) and 73 bone marrow (BM) samples from 54 patients with CML at diagnosis, during imatinib and dasatinib therapies. Leukocytes and lymphocyte subclasses were analyzed with an extensive flow cytometry panel including markers for activation, differentiation and memory status. At diagnosis, a lower proportion of B cells and dendritic cells and an increased amount of NKT‐like cells were detected in the BM. During imatinib therapy, all these changes normalized and the immunoprofile resembled healthy controls. However, dasatinib patients were clearly divided into two distinct groups: one similar to healthy controls and the other showing immunoactivation characterized by significant elevations of CD8+, NK‐ and NKT‐like cells in PB. T cells of the latter group strongly expressed CD57+, HLA‐DR and CD45RO and had low CD62L antigen levels characteristic of late memory cytotoxic lymphocytes. Our results indicate that while both TKIs show immunosuppressive effects in vitro, they have a significant and differential effect on the numbers and proportions of immune effector cells in vivo. In particular, in a distinct subgroup of dasatinib‐treated patients, immune reactivity is markedly enhanced warranting careful follow‐up.
Assessment of bone marrow involvement in non‐Hodgkin’s lymphomas: comparison between histology and flow cytometry
Authors: Merli Michele , Arcaini Luca , Boveri Emanuela , Rattotti Sara , Picone Cristina , Passamonti Francesco , Tenore Annamaria , Sozzani Laura , Lucioni Marco , Varettoni Marzia , Rizzi Silvia , Morello Lucia , Ferretti Virginia , Pascutto Cristiana , Paulli Marco , Lazzarino Mario
Published: July 2010

Bone marrow (BM) examination is essential in the staging of non‐Hodgkin’s lymphoma (NHL) patients. Few studies have compared BM histologic findings with results of flow cytometric (FC) analysis. We analyzed the incidence and patterns of histologic BM involvement in a series of 753 patients with NHL. For 498 patients, a concurrent FC analysis on BM was available. Histologic involvement was detected at diagnosis in 311/753 (41%) patients. By FC, BM involvement was clearly detected in 150/498 (30%). After excluding 12 cases with equivocal histology, concordance between the two methods was detected in 411 (85%) cases (27% BMB+/FC+; 58% BMB−/FC−), while discordance was present in 75 (15%) (P < 0.001): 58 cases (12%) were BMB+/FC− and 17 (3%) were BMB−/FC+. Discordance was more frequent in FL and in lymphoplasmacytic lymphoma (LPL). These data demonstrate that the two methods are comparable in qualitative assessment of BM involvement in NHL, with the exception of FL and LPL. In FL, diffuse large B‐cell lymphoma (DLBCL) and LPL, FC underestimates the extent of infiltrate with respect to histology.
Up‐regulation of TNF‐alpha secretion by cigarette smoke is mediated by Egr‐1 in HaCaT human keratinocytes
Authors: Jeong Sang Hoon , Park Jae Hong , Kim Ji Na , Park Yoon‐Hee , Shin Soon Young , Lee Young Han , Kye Young Chul , Son Sang Wook
Published: July 2010

Please cite this paper as: Up‐regulation of TNF‐alpha secretion by cigarette smoke is mediated by Egr‐1 in HaCaT human keratinocytes. Experimental Dermatology 2010; 19: e206–e212.

Abstract:  Many epidemiologic studies have pointed to a significant association between cigarette smoking and inflammatory skin disease such as psoriasis. Cigarette smoke induces expression of regulators of inflammation such as interleukin (IL)‐1, IL‐6, IL‐8 and tumor necrosis factor (TNF)‐α. It was recently demonstrated that early growth response‐1 (Egr‐1) transcription factor is significantly up‐regulated in the skin lesions of patients with psoriasis. The mechanism by which cigarette smoke extract (CSE) regulates inflammatory cytokine expression in keratinocyte was still unknown. The aim of this study was to investigate the signalling of CSE‐induced Egr‐1 expression and the role for Egr‐1 in CSE‐induced TNF‐α expression. Cytotoxicity of CSE in HaCaT cells was measured by thiazolyl blue tetrazolium bromide (MTT) assay. CSE‐induced Egr‐1 expression was investigated by western blot, luciferase reporter assay and confocal microscopy. TNF‐α expression was measured by reverse transcription‐polymerase chain reaction and enzyme‐linked immunosorbent assay. Involvement of Egr‐1 in CSE‐induced TNF‐α secretion was determined by using Egr‐1 specific siRNA. CSE increases the Egr‐1 expression, promoter activity and its nuclear translocation in human HaCaT keratinocytes. CSE activates mitogen‐activated protein kinase (MAPK) pathways including extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK). Up‐regulation of Egr‐1 expression by CSE stimulation was found to be inhibited by an ERK and JNK but not p38 inhibitor. CSE increases TNF‐α expression and secretion. This increase is mediated by CSE‐induced Egr‐1 expression. Our results showed that CSE induces Egr‐1 expression via MAPK pathway in human keratinocytes and TNF‐α expression by Egr‐1. This pathway may contribute to the development of inflammatory disease such as psoriasis.
An unexpected twist in alopecia areata pathogenesis: are NK cells protective and CD49b+ T cells pathogenic?
Authors: Kaufman Gil , D’Ovidio Roberto , Kaldawy Anis , Assy Bedia , Ullmann Yehuda , Etzioni Amos , Paus Ralf , Gilhar Amos
Published: July 2010

Please cite this paper as: An unexpected twist in alopecia areata pathogenesis: are NK cells protective and CD49b+ T cells pathogenic? Experimental Dermatology 2010; 19: e347–e349.

Abstract:  Natural killer (NK) cells have become a recent focus of interest in alopecia areata (AA) research. To further investigate their role in an established mouse model of AA, lesional skin from older C3H/HeJ mice with AA was grafted to young C3H/HeJ female mice, and NK cells were depleted by continuous administration of rabbit anti‐asialo GM1. As expected, this significantly reduced the number of pure NK cells in murine skin, as assessed by NKp46 quantitative immunohistochemistry. Quite unexpectedly, however, the onset of hair loss in C3H/HeJ mice was accelerated, rather than retarded. NK cell depletion was accompanied by a significant increase in the number of perifollicular CD49b+T cells in the alopecic skin of anti‐asialo GM1‐treated mice. These findings underscore the need to carefully distinguish in future AA research between pure NK cells and defined subsets of CD49b+ lymphocytes, as they may exert diametrically opposed functions in hair follicle immunology and immunopathology.
Classical altitude training
Authors: Friedmann‐Bette B.
Published: July 2010

For more than 40 years, the effects of classical altitude training on sea‐level performance have been the subject of many scientific investigations in individual endurance sports. To our knowledge, no studies have been performed in team sports like football. Two well‐controlled studies showed that living and training at an altitude of ≥1800–2700 m for 3–4 weeks is superior to equivalent training at sea level in well‐trained athletes. Most of the controlled studies with elite athletes did not reveal such an effect. However, the results of some uncontrolled studies indicate that sea‐level performance might be enhanced after altitude training also in elite athletes. Whether hypoxia provides an additional stimulus for muscular adaptation, when training is performed with equal intensity compared with sea‐level training is not known. There is some evidence for an augmentation of total hemoglobin mass after classical altitude training with duration ≥3 weeks at an altitude ≥2000 m due to altitude acclimatization. Considerable individual variation is observed in the erythropoietic response to hypoxia and in the hypoxia‐induced reduction of aerobic performance capacity during training at altitude, both of which are thought to contribute to inter‐individual variation in the improvement of sea‐level performance after altitude training.
Pityriasis rubra pilaris – a retrospective single center analysis over eight years
Authors: Gemmeke Astrid , Schönlebe Jaqueline , Koch André , Wollina Uwe
Published: July 2010

Background: Pityriasis rubra pilaris (PRP) is a rare papulosquamous dermatosis. We evaluated evaluate co‐morbidities, complications, and outcome of treatment regimens.

Patients and Methods: This is a retrospective study at an academic teaching hospital. We analyzed all patients with the definite diagnosis of PRP seen since 2001. Epidemiologic data, co‐morbidities, response to and course during treatment were investigated.

Results: We identified 10 PRP‐patients (6 men, 4 women), mean age 56.4 years, with type I (n = 9) and type IV (n = 1). Three patients had internal co‐morbidities (atrial fibrillation with cardiac insufficiency, dilated cardiomyopathy, diabetes mellitus). Two patients needed psychiatric treatment because of depression. PRP caused ectropium (2 ×), diffuse effluvium (1 ×), and stenosis of the outer ear canal (1 ×). We did not observe a spontaneous remission. Among 9 patients with PRP type I, five were treated with acitretin (two of them as Re‐PUVA), and two with methotrexate (in one patient combined with fumaric acids). Systemic corticosteroids were not effective. One patient was treated with infliximab i.v., 5 mg/kg body weight. Starting with the first application, inflammatory activity decreased and erythema got paler. The treatment was well tolerated.

Conclusions: PRP type I is a severe, chronic inflammatory dermatosis responding hesitantly to classic systemic therapies. Tumor necrosis factor‐α antagonists are an effective treatment option for difficult cases.
Calcium antagonists, diltiazem and nifedipine, protect broilers against low temperature‐induced pulmonary hypertension and pulmonary vascular remodeling
Authors: YANG Ying , GAO Mingyu , GUO Yuming , QIAO Jian
Published: July 2010

This study was designed to determine whether calcium antagonists, diltiazem and nifedipine, can depress low temperature‐induced pulmonary hypertension (PH) in broilers (also known as ascites) and to characterize their efficacy on hemodynamics and pulmonary artery function. Chicks were randomly allocated into six experimental groups and orally administered with vehicle, 5.0 mg/kg body weight (BW)/12 h nifedipine or 15.0 mg/kg BW/12 h diltiazem from 16 to 43 days of age under low temperature. The mean pulmonary arterial pressure (mPAP), the ascites heart index (AHI), the erythrocyte packed cell volume (PCV) and the relative percentage of medial pulmonary artery thickness were examined on days 29, 36 and 43. The data showed that administration of diltiazem protected broilers from low temperature‐induced pulmonary hypertension and vascular remodeling. Although nifedipine prevented mPAP from increasing during the early stage, it did not suppress the development of PH during the late stage and did not keep heart rate (HR), PCV, AHI and the thickness of pulmonary small artery smooth muscle layer at the normal levels. Taken together, our results showed that diltiazem can effectively prevent low temperature‐induced pulmonary hypertension in broilers with fewer side‐effects and may be a potential compound for the prevention of this disease in poultry industry.
Systems approaches to beef cattle production systems using modeling and simulation
Authors: HIROOKA Hiroyuki
Published: July 2010

Systems approach techniques have been applied to modeling production systems for beef cattle from the relatively micro‐level of tissues and organs to the macro‐level of farms and geographical regions. This paper reviews the various types of beef cattle production models already in operation in order to analyze beef cattle production systems and their components. It may be theoretically possible to construct system models which describe such complex production systems and can be generally used in various genetic, nutritional, management and economic situations as well as in training, extension and educational programs. Moreover, the systems approach can assist in the organization of information and identification of knowledge gaps and thereby open an avenue to multi‐disciplinary research projects.
Basic characterization of 90 kDa heat shock protein genes HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 expressed in Japanese quail (Coturnix japonica)
Authors: NAGAHORI Kohji , IWAMOTO Shigehisa , MARUYAMA Akira , SUZUKI Shingo , HOSOMICHI Kazuyoshi , SHIINA Takashi , HARA Hiromi , YOSHIDA Yutaka , HANZAWA Kei
Published: July 2010

In the current study, we describe four novel members of the 90 kDa heat shock protein (HSP90) family expressed in Japanese quail, Coturnix japonica. The coding regions of the genes, CjHSP90AA1, CjHSP90AB1, CjHSP90B1 and CjTRAP1, exhibited more than 94% similarity to their related genes in chicken. The putative proteins encoded by these quail genes contained motifs considered essential for HSP90 gene function. In addition, the predicted proteins were more similar to HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 proteins expressed in vertebrates than they were to other members of the HSP90 family. Exon numbers of CjHSP90AA1 (11), CjHSP90AB1 (12) or CjTRAP1 (18) are the same as the chicken and mammalian orthologs. Furthermore, gene order in the regions surrounding CjHSP90AB1 and CjTRAP1 has been preserved, providing evidence that the genomic regions were orthologous to HSP90‐containing regions in the chicken genome. The promoter regions of the genes also contained conserved motifs identified in related genes of chicken. However, the nucleotide sequences of the 5′‐flanking region of these genes were highly polymorphic. We also found that CjHSP90AA1 exhibited a robust response to heat shock treatment. Taken together, the data suggest that CjHSP90AA1, CjHSP90AB1, CjHSP90B1 and CjTRAP1 encode orthologs of HSP90AA1, HSP90AB1, HSP90B1 and TRAP1, respectively.
Motives for Outward FDI of Chinese Private Firms Firm Resources, Industry Dynamics, and Government Policies
Authors: Lu Jiangyong , Liu Xiaohui , Wang Hongling
Published: July 2010

Using recent survey data, this study examines the impact of firm resources, industry dynamics, and government policies on the outward foreign direct investment (FDI) motives of Chinese firms, based on the integrated ‘strategy tripod’ framework. The results suggest that supportive government policies are important motivators for both strategic asset-seeking and market-seeking outward FDI. Firms' technology-based competitive advantages and a high level of industry research and development (R&D) intensity tend to motivate strategic asset-seeking outward FDI, whereas firm's export experience and higher level of domestic industry competition tend to induce market-seeking outward FDI.
Putting Strategic Human Resource Management in Context: A Contextualized Model of High Commitment Work Systems and Its Implications in China
Authors: Kim Sunghoon , Wright Patrick M.
Published: July 2010

This study contributes to strategic human resource management (HRM) research by offering a contextualized model of HRM effectiveness. Building on HR attribution theory, we propose that the high commitment work system will be more effective in a context when: (i) employees are conditioned to trust employers and (ii) regulatory institutions are less restrictive, giving management more autonomy in human resource decisions. In such contexts, we argue that employees are more inclined to view the high commitment work system as an expression of the employer's genuine concern for employees. Hence, employees are more likely to reciprocate with high commitment. We find our contextualized HRM effectiveness model particularly useful in understanding HRM – firm performance relations in China where business environments are currently under transformation on both trust and regulations.
Families With Children and Adolescents: A Review, Critique, and Future Agenda
Authors: Crosnoe Robert , Cavanagh Shannon E.
Published: July 2010

This decade's literature on families with children and adolescents can be broadly organized around the implications for youth of family statuses (e.g., family structure) and family processes (e.g., parenting). These overlapping bodies of research built on past work by emphasizing the dynamic nature of family life and the intersection of families with other ecological settings, exploring race/ethnic diversity, identifying mechanisms connecting family and child/adolescent factors, and taking steps to address the threats to causal inference that have long been a problem for family studies. Continuing these trends in the future will be valuable, as will increasing the number of international comparisons, exploring “new” kinds of family diversity, and capturing the convergence of multiple statuses and processes over time.
Parenthood, Childlessness, and Well‐Being: A Life Course Perspective
Authors: Umberson Debra , Pudrovska Tetyana , Reczek Corinne
Published: July 2010

This article reviews recent research (1999–2009) on the effects of parenthood on well‐being. We use a life course framework to consider how parenting and childlessness influence well‐being throughout the adult life course. We place particular emphasis on social contexts and how the impact of parenthood on well‐being depends on marital status, gender, race/ethnicity, and socioeconomic status. We also consider how recent demographic shifts lead to new family arrangements that have implications for parenthood and well‐being. These include stepparenting, parenting of grandchildren, and childlessness across the life course.
Conflict, Power, and Violence in Families
Authors: Anderson Kristin L.
Published: July 2010

Research on conflict, power, and violence in families in the 2000s developed a promising focus on the interconnections between types of violence and between the experience of violence and locations in larger structures of power and inequality. I examine research on poly‐victimization, typologies of violence, dyadic research, and links between violence and inequalities of gender, race, class, and sexual orientation. Additionally, this review evaluates research on the connections between violence in families and other arenas of family study, including teen pregnancy, marriage formation, cohabitation, and divorce. The review concludes with a discussion of studies showing declines in rates of abuse within families in the 2000s.
Advances in Families and Health Research in the 21st Century
Authors: Carr Deborah , Springer Kristen W.
Published: July 2010

We review research on families and health published between 2000 and 2009 and highlight key themes and findings from innovative, methodologically rigorous studies. Whereas research in prior decades focused primarily on whether family structure affects child and adult health, contemporary research examines the contextual and processual factors that shape for whom, for which outcomes, and under what conditions families affect mental and physical health. We discuss how family structure, transitions, and processes within families of origin affect children's health over the life course. We then examine the effects of marital status, transitions, and quality for adult health. We point out limitations in current research, discuss implications of recent findings for policy, and highlight theoretical and methodological directions for future research.
Dose rounding of chemotherapy in colorectal cancer: An analysis of clinician attitudes and the potential impact on treatment costs
Authors: FIELD Kathryn , ZELENKO Anna , KOSMIDER Suzanne , COURT Karen , NG Li‐Ling , HIBBERT Marienne , GIBBS Peter
Published: July 2010

Aim:  The aims of this study were to calculate theoretical cost savings of oxaliplatin dose rounding in colorectal cancer (CRC), and to assess clinician attitudes to chemotherapy dose rounding.

Methods:  Data were obtained from a prospective data repository (BioGrid Australia) from four hospitals regarding the use of oxaliplatin, given at a standard dose of 85 mg/m2. We examined potential cost savings for patients with a body surface area (BSA) between 1.77 m2 and 1.94 m2, resulting in a calculated dose up to 10% above 150 mg (a 100 mg and 50 mg vial). The attitudes of oncologists at these hospitals toward minor dose reductions were assessed.

Results:  From January 2003 to June 2008, of 676 patients with Stages III or IV CRC, 227 (33.58%) received oxaliplatin. Overall 66 patients (29%) had a calculated BSA between 1.77 m2 and 1.94 m2. The potential cost saving for these hospitals in one year, if oxaliplatin doses were rounded down to 150 mg, is $AU51 898. Extrapolated to the Australian population, estimated savings are over $AU2.5 million per year. Three of nine (33.3%) oncologists were comfortable with an initial dose reduction of up to 10% in the adjuvant disease setting, and seven of nine (77.8%) in the setting of metastatic disease.

Conclusion:  Minor dose reductions for CRC to accommodate vial sizes would lead to significant cost savings. Oncologists are more comfortable with minor dose reductions when treatment is given in a palliative setting.
Cytoskeletal control of vesicle transport and exocytosis in chromaffin cells
Authors: Trifaró J.‐M. , Gasman S. , Gutiérrez L. M.
Published: July 2010

Chromaffin cell exocytosis is a fascinating interplay between secretory vesicles and cellular components. One of these components is the cytoskeleton and its associated regulatory proteins. Transport of chromaffin secretory granules from their site of biosynthesis towards the active site of exocytosis requires both F‐actin fine remodelling as well as microtubule trails. At least two molecular motors, myosins II and V, seem to play a crucial role in the control of F‐actin dynamics and vectorial vesicle displacement respectively. Vesicle movement experiences spatial restrictions as they approach the cell cortical region, where the F‐actin meshwork constitutes a barrier‐limiting vesicle access to the plasmalemma. During secretion, cortical F‐actin is locally disrupted providing access of vesicles to release sites on the plasmalemma. Removal of the stimulus restores cortical F‐actin. Two pathways (Ca2+‐ scinderin and PKC‐MARCKS) control F‐actin changes during the secretory cycle . Furthermore, GTPases such as RhoA, that controls F‐actin network integrity, and Cdc42 signalling which induces the formation of local actin filaments at active sites, provide additional evidence on the importance of F‐actin as a key element in vesicle transport and in the exocytotic machinery of chromaffin cells.
Oxidative Damage, Bleomycin, and Gamma Radiation Induce Different Types of DNA Strand Breaks in Normal Lymphocytes and Thymocytes: A Comet Assay Study
Authors: BENÍTEZ‐BRIBIESCA LUIS , SÁNCHEZ‐SUÁREZ PATRICIA
Published: July 2010

Most anticancer treatments such as chemo‐ and radiotherapy induce DNA damage and apoptosis in normal cells. The aim of this study was to assess the induction of single and double DNA strand breaks (ssb and dsb, respectively) and apoptosis in normal human lymphocytes and rat thymocytes subjected to the action of H2O2, bleomycin and ionizing radiation. Normal human peripheral thymocytes and young rat thymocytes were subjected to the following treatments: a) H2O2; b) bleomycin, and c) γ‐radiation, all with various doses. DNA strand breaks were studied with the alkaline and neutral comet assay for detection of ssb and dsb. Apoptosis was quantified morphologically and with DNA agarose gel electrophoresis. After H2O2 treatment, a dose‐dependent increase of ssb was observed. Bleomycin treatment produced a moderate increase of ssb at lower concentrations and a striking increase of dsb at higher concentrations that coincided with the presence of apoptosis and DNA ladders. Gamma radiation initially induced the formation of ssb, and after three hours an increase of dsb in a dose‐dependent manner. Apoptosis and DNA laddering appeared only 3 hours post‐irradiation. The biomonitoring of DNA damage inflicted by antineoplastic agents can be easily performed with the comet assay and could be useful to monitor and modulate chemo‐ and radiotherapeutic regimes in cancer patients.
The Role of Proopiomelanocortin‐Derived Peptides in Skin Fibroblast and Mast Cell Functions
Authors: TEOFOLI PATRIZIA , FREZZOLINI ALESSANDRA , PUDDU PIETRO , De PITÀ ORNELLA , MAUVIEL ALAIN , LOTTI TORELLO
Published: July 2010

ABSTRACT: We have previously described proopiomelanocortin (POMC) gene‐expression in human normal cultured dermal fibroblasts, and its dose‐ and time‐dependent modulation by transforming growth factor‐β (TGF‐β) and tumor necrosis factor‐α (TNF‐α). The aim of the work described here was to investigate POMC‐derived peptide release in vitro by cultured fibroblasts following incubation with different concentrations of both TNF‐α and TGF‐β for 24 hours (1, 5, and 10 ng/ml). The effect of simultaneous addition of both TNF‐α and TGF‐β (10 ng/ml) was also evaluated. Culture supernatants of human skin fibroblasts were collected to detect adrenocorticotropin hormone (ACTH), α‐melanotropin (α‐MSH), and β‐endorphin (β‐EP) levels by specific immunoenzymatic assay. We investigated the in vitro histamine‐releasing activity of the POMC‐derived peptides, α‐MSH and β‐EP, on human foreskin mast cells. Detection of cleavage products in supernatants from cultured normal human dermal fibroblasts indicated intracellular processing by POMC protein. We were able to measure detectable levels of all peptides in basal conditions. TNF‐α addition resulted in an increase in β‐EP and ACTH levels. TGF‐β‐stimulated fibroblasts showed no alteration in β‐EP and α‐MSH levels, whereas ACTH release was significantly enhanced. Both α‐MSH and β‐EP induced histamine release from human foreskin mast cells in vitro with β‐EP‐induced histamine levels as high as those observed with the calcium ionophore, ionomycin. Our data document fibroblast POMC‐derived peptide release and modulation by cytokines, suggesting that they have a possible role in extracellular matrix deposit regulation and skin inflammation.
Vaccination against Bovine Babesiosis
Authors: DE VOS ALBERTUS J. , BOCK RUSSELL E.
Published: July 2010

Abstract: Bovine babesiosis is an important disease caused by Babesia bovis, B. bigemina, and B. divergens. Solid immunity develops after infection and this feature has been exploited with the use of live attenuated organisms as immunogens. Attributes of live vaccines include a durable immunity to heterologous challenge after one vaccination. To overcome disadvantages relating to poor quality control (risk of contamination and adverse reactions), production procedures have been modified to meet the requirements of codes of good manufacturing practice. This includes development of methods to allow production of cryopreserved vaccine and limit antigenic drift. Killed vaccines have also been used on a limited basis and consist of antigens extracted from cultured material or blood of infected calves, and given with adjuvant. The degree and duration of immunity against heterologous challenge is not well documented. Attempts are being made to develop subunit vaccines but the progress has been slow. A better understanding of the mechanisms involved in the expression of protective immunity against Babesia spp will aid in the identification of protective antigens.
Regulation of Cytokine Secretion and Amyloid Precursor Protein Processing by Proinflammatory Amyloid Beta (Aβ)
Authors: GITTER BRUCE D. , BOGGS LEONARD N. , MAY PATRICK C. , CZILLI DAN L. , CARLSON CHRISTOPHER D.
Published: July 2010

Abstract:Neurodegenerative processes in Alzheimer's disease (AD) are thought to be driven, in part, by the deposition of amyloid beta (Aβ), a 39‐43‐aminoacid peptide product resulting from an alternative cleavage of amyloid precursor protein (APP). In addition to its neurotoxic properties, Aβ may influence neuropathology by stimulating glial cell cytokine and acute phase protein secretion in affected areas of the brain (e.g., cortex, hippocampus). Using anin vitrohuman astrocyte model (U‐373 MG astrocytoma cells), the effects of Aβ treatment on acute phase protein (APP and alpha‐1‐antichymot rypsin [α1‐ACT]) and interleukin‐8 (IL‐8) were examined. U‐373 MG cells secreted increased levels of α1‐ACT and neurotrophic/neuroprotective alpha‐cleaved APP (αAPP) after exposure to interleukin‐1β (IL‐1β) for 24 hours. Aβ treatment resulted in a similar, but modest increase in α1‐ACT secretion, a two‐ to threefold stimulation of IL‐8 production, and, conversely, a profound reduction in the levels of secreted αAPPs. Aβ inhibited αAPP secretion by U‐373 MG cells in a concentration‐ and conformation‐dependent manner. Moreover, the reduction in αAPP secretion was accompanied by an increase in cell‐associated APP. Another proinflammatory amyloidogenic peptide, human amylin, similarly affected APP processing in U‐373 astrocytoma cells. These data suggest that Aβ may contribute to Alzheimer's‐associated neuropathology by lowering the production of neuroprotective/neurotrophic αAPPs. Moreover, the concomitant increase in cell‐associated APP may provide increased substrate for the generation of amyloidogenic peptides within astrocytes.
Nerve‐Driven Immunity: The Direct Effects of Neurotransmitters on T‐Cell Function
Authors: LEVITE MIA
Published: July 2010

Abstract:We carried out studies to explore whether neurotransmitters can directly interact with their T‐cell‐expressed receptors, leading to either activation or suppression of various T‐cell functions. Human and mouse T cells were thus exposed directly to neurotransmitters in the absence of any additional molecule, and various functions were studied, among them cytokine secretion, proliferation, and integrin‐mediated adhesion and migration. In this review, I describe the effects of four neuropeptides: somatostatin (SOM), calcitonin‐gene‐related‐peptide (CGRP), neuropeptide Y (NPY), and substance P (Sub P), and one non‐peptidergic neurotransmitter‐dopamine. We found that SOM, NPY, CGRP, and dopamine interact directly with T cells, leading to the activation of β1integrins and to the subsequent integrin‐mediated T‐cell adhesion to a component of the extracellular matrix. In contrast, Sub P had a reverse effect‐full blockage of integrin‐mediated T‐cell adhesion triggered by a variety of signals. Each of these neurotransmitters exerted its effect through direct interaction with its specific receptor on the T‐cell surface, since the effect was fully blocked by the respective receptor‐antagonist. Taken together, this set of findings indicates that neurotransmitters can directly interact with T cells and provide them with either positive (integrin‐activating, pro‐adhesive) or negative (integrin‐inhibiting, anti‐adhesive) signals. We further found that the above neurotransmitters, by direct interaction with their specific receptors, drove T cells (of the Th0, Th1, and Th2 phenotypes) into the secretion of both typical and atypical (“forbidden”) cytokines. These results suggested that neurotransmitters can substantially affect various cytokine‐dependent T‐cell activities. As a whole, our studies suggest an important and yet unrecognized role for neurotransmitters in directly dictating or modulating numerous T‐cell functions under physiological and pathological conditions.
Pulmonary Phenotype of CCSP/UG Deficient Mice: A Consequence of CCSP Deficiency or Altered Clara Cell Function?
Authors: STRIPP BARRY R. , REYNOLDS SUSAN D. , PLOPPER CHARLES G. , BØE INGER‐MARGRETHE , LUND JOHAN
Published: July 2010

Abstract:Clara cell secretory protein (CCSP) is the most abundant secreted protein within airways of the lung. Moreover, CCSP levels are modulated in human lung disease, supporting a potentially important role for CCSP and/or Clara cells in lung homeostasis. However,in vivoroles for CCSP remain elusive. A popular hypothesis is that CCSP is a regulator of the inflammatory response. The purpose of this review is to provide an overview of the phenotype of CCSP null mice and relate this phenotype to proposed functions for the protein. Phenotypic analysis of mice homozygous for the CCSP‐1 null allele of the CCSP gene (CCSP−/−1) revealed susceptibility to inhaled oxidant gases. Sensitivity of CCSP−/−1 mice to inhaled ozone is unrelated to alterations in antioxidant defenses, but is associated with increased cellular injury. Additional studies investigating inflammatory control in CCSP deficient mice found no differences between wild‐type and CCSP−/−1 mice in their inflammatory response to low‐dose inhaled endotoxin exposure, arguing against a role for CCSP in regulation of pulmonary inflammation. The findings among CCSP−/−1 mice of ultrastructural alterations to Clara cell secretory apparatus, with associated changes in airway lining fluid protein composition, demonstrate that the CCSP−/−1 genotype results in more complex changes to airways than CCSP deficiency per se. It can be concluded that CCSP does not regulate endotoxin‐induced pulmonary inflammation. Moreover, CCSP−/−1 mice represent a valuable tool for probing functional roles for Clara cells in regulation of airway lining fluid composition and lung pollutant susceptibility.
Working toward an Ethical Anthropology: Where Do We Go from Here?
Authors: BRUCE BEVERLEE
Published: July 2010

Abstract: This article posits an ethical anthropology for the 21st century that addresses and informs our understanding of international conflict situations and their solutions while providing methodologies for anthropologists of color to position their issues of concern at the center of social science discourse.
Protein Oxidation
Authors: STADTMAN EARL R. , LEVINE RODNEY L.
Published: July 2010

Abstract: The oxidative modification of proteins by reactive species, especially reactive oxygen species, is implicated in the etiology or progression of a panoply of disorders and diseases. These reactive species form through a large number of physiological and non‐physiological reactions. An increase in the rate of their production or a decrease in their rate of scavenging will increase the oxidative modification of cellular molecules, including proteins. For the most part, oxidatively modified proteins are not repaired and must be removed by proteolytic degradation, and a decrease in the efficiency of proteolysis will cause an increase in the cellular content of oxidatively modified proteins. The level of these modified molecules can be quantitated by measurement of the protein carbonyl content, which has been shown to increase in a variety of diseases and processes, most notably during aging. Accumulation of modified proteins disrupts cellular function either by loss of catalytic and structural integrity or by interruption of regulatory pathways.
Waist Circumference and Sagittal Diameter Reflect Total Body Fat Better Than Visceral Fat in Older Men and Women: The Health, Aging and Body Composition Study
Authors: HARRIS TAMARA B. , VISSER MARJOLEIN , EVERHART JAMES , CAULEY JANE , TYLAVSKY FRANCES , FUERST THOMAS , ZAMBONI MAURO , TAAFFE DENNIS , RESNICK HELAINE E. , SCHERZINGER ANN , NEVITT MICHAEL ,   FOR THE HEALTH, AGING AND BODY COMPOSITION STUDY
Published: July 2010

Abstract: The validity of waist circumference and sagittal diameter as surrogate measures of visceral fat were assessed using preliminary cross‐sectional data from the Health, Aging and Body Composition Study, a cohort of 3,075 men and women aged 70–79. Weight, body mass index, waist circumference, waist/thigh ratio, and sagittal diameter were compared by correlation, graphical analysis, and regression to total body fat as measured by dual‐energy X‐ray absorptiometry (Hologic 4500A), and to visceral fat area as measured by computerized tomography. We included 2,830 persons, 1,439 women and 1,391 men with complete data on all measurements. For both men and women, all measurements were strongly correlated with both total body fat and visceral fat except the waist/thigh ratio. However, waist circumference, sagittal diameter, weight, and body mass index were more closely related to total body fat than to visceral fat area (R2 for the linear regression of waist circumference on total body fat was 0.69 in women and men; R2 for linear regression of waist circumference on visceral fat area was 0.40 in women, and 0.49 in men). These data suggest that the contribution of visceral fat to health risks will be better assessed by directly measuring this fat depot.
The Epigenetics of Colorectal Cancer
Authors: ISSA JEAN‐PIERRE
Published: July 2010

Abstract: Colorectal cancer has provided an excellent model for studying the genetic basis of cancer and is one of the better‐understood malignancies in this regard. The orderly progression of the disease, with distinct genetic alterations at each step, is a useful framework for deciphering the molecular basis of neoplasia. Epigenetics, the study of clonal changes in gene expression without associated genetic lesions, has raised increased interest recently, in part because of the identification of DNA methylation as a potential molecular mediator of the process. Several tumor‐suppressor genes are silenced in various neoplasms in association with aberrant promoter methylation, and in the absence of coding region mutations. The study of DNA methylation changes in colorectal cancer has now provided additional clues into the pathogenesis of the disease. This review presents evidence for a model whereby DNA methylation changes play two distinct roles in the molecular evolution of colorectal cancer. Initially, progressive methylation and silencing of a subset of genes takes place in normal tissues as a function of age or time‐dependent events and predisposes these normal cells to neoplastic transformation. At a later stage of disease progression, DNA methylation plays an important role in a subset of tumors affected by the CpG island methylator phenotype (CIMP), a recently identified pathway that results in a form of epigenetic instability through the simultaneous silencing of multiple genes. DNA methylation changes have important interactions with genetic lesions in this cancer type. CIMP? cancers include the majority of tumors with sporadic mismatch repair deficiency through hypermethylation of the hMLH1 promoter, and also account for the majority of tumors with Ki‐ras mutations through an unknown mechanism. By contrast, CIMP− cases evolve along a more classic genetic instability pathway, with a high rate of p53 mutations and chromosomal changes. Thus, the integration of epigenetic and genetic information provides a more complete molecular understanding of colorectal cancer and may have implications for the diagnosis, prognosis, and treatment of patients affected by this disease.
CO2 Hydrate Formation in Various Hydrodynamic Conditions
Authors: YAMASAKI A. , TENG H. , WAKATSUKI M. , YANAGISAWA Y. , YAMADA K.
Published: July 2010

Abstract: The influence of hydrodynamics on formation of CO2 hydrate in a column‐type reactor and a stirred‐vessel reactor was investigated experimentally. In the column‐type reactor, the buoyant motion of the CO2 drops released into the reactor was balanced by the counterflow of the water in the reactor and, therefore, the CO2 drops were suspended stably in the test column. The drop Reynolds number affected hydrate formation significantly. For drops with small Reynolds numbers, hydrate formed almost immediately on the drops. For drops with large Reynolds numbers, it took up to 20 minutes for hydrate to cover the drops. In cases where the Reynolds number reached a certain critical value, a continuous process of hydrate formation on the drops and hydrate shedding from the drops was observed. In the stirred‐vessel reactor, the kinetics of hydrate formation was governed by the strength of agitation. In cases without agitation, hydrate formed only at the liquid CO2‐water interface. In cases with a weak agitation, hydrate was shed from the interface; however, the interface was still the only location for hydrate formation. In cases with a strong agitation, the liquid CO2‐water interface broke, liquid CO2 dispersed throughout the water phase, and hydrate particles of about 0.1 mm in size formed in water simultaneously. The hydrate particles and dispersed CO2 drops coagulated, forming a cluster with a dimension of a few centimeters when stirring was stopped. The bulk density of the cluster varied with the duration of agitation. At early stages, the bulk density of the cluster was less than that of water; however, it increased with time under a continuous agitation. The critical time of duration, at which buoyancy of the cluster changed from positive to negative, decreased dramatically with increase in the rate of agitation.
Thermodynamic Inhibitors for Hydrate Plug Melting
Authors: LI XIAOYUN , GJERTSEN LARS HENRIK , AUSTVIK TORSTEIN
Published: July 2010

Abstract: The hydrate melting efficiency of thermodynamic inhibitors has been shown to depend on hydrate plug properties, inhibitor properties, and the turbulence of the liquid system in question. Inefficient mixing of inhibitor and water, lack of contact between inhibitor and hydrate, and a solid or gel precipitation in the melting region have been demonstrated to give low melting efficiency. MeOH seems to be the most efficient inhibitor for melting porous plugs, but may not melt a plug with low porosity. MEG has the ability to penetrate into a compact plug and cause melting. However, when used at high concentrations, MEG may freeze out as a solid or gel, which can lead to reduced hydrate melting efficiency. At high pressures and in the presence of a hydrocarbon liquid, MEG solutions were shown to freeze out at temperatures more than 30°C higher than values given in the literature. TEG seems to easily freeze and become inefficient for melting hydrate plugs.
Laboratory Measurements of Compressional and Shear Wave Speeds through Methane Hydrate
Authors: WAITE WILLIAM F. , HELGERUD MICHAEL B. , NUR AMOS , PINKSTON JOHN C. , STERN LAURA A. , KIRBY STEPHEN H. , DURHAM WILLIAM B.
Published: July 2010

Abstract: Simultaneous measurements of compressional and shear wave speeds through polycrystalline methane hydrate have been made. Methane hydrate, grown directly in a wave speed measurement chamber, was uniaxially compacted to a final porosity below 2%. At 277 K, the compacted material had a compressional wave speed of 3,650 ± 50 m/s. The shear wave speed, measured simultaneously, was 1,890 ± 30 m/s. From these wave speed measurements, we derive Vp/Vs, Poisson's ratio, bulk, shear, and Young's moduli.
Differential Activation of Phospholipase D by VPAC and PAC1 Receptors
Authors: McCULLOCH D. A. , LUTZ E. M. , JOHNSON M. S. , MacKENZIE C. J. , MITCHELL R.
Published: July 2010

Abstract: To investigate the phospholipase D (PLD) responses of the VIP/PACAP receptors, VPAC1 and VPAC2, and the PACAP‐specific PAC1 receptors (short and “hop” intracellular loop 3 (i3) splice variants), stable CHO cell lines expressing similar levels of each wildtype receptor were generated (except for the VPAC1 receptor clone which showed considerably lower expression and lesser responses in signalling assays). All clones caused activation of PLD in response to agonists, as monitored by [3H]phosphatidylbutanol production. The PLD responses of the PAC1“hop”, but not the “null” receptor, were sensitive to the ARF inhibitor, brefeldin A (BFA) (as were VPAC1 and VPAC2 responses). Chimeric constructs of VPAC2 receptors containing i3 of either PAC1 hop or PAC1 null receptors were transiently expressed in COS 7 cells and PLD responses were measured. Only the PLD response of the hop construct was sensitive to BFA. This suggests that i3 motifs in certain Group II GPCRs may play a key role in determining their linkage to ARF‐dependent PLD activation.
Mechanisms of DNA Topoisomerase I‐Induced Cell Killing in the Yeast:Saccharomyces cerevisiae
Authors: FIORANI PAOLA , BJORNSTI MARY‐ANN
Published: July 2010

Abstract:DNA topoisomerase I (Top1) catalyzes the relaxation of supercoiled DNA by a mechanism of transient DNA strand cleavage characterized by the formation of a phosphotyrosyl bond between the DNA end and active site tyrosine. Camptothecin reversibly stabilizes the covalent enzyme‐DNA intermediate by inhibiting DNA religation. During S‐phase, collisions with advancing replication forks convert these complexes into potentially lethal lesions. To define the DNA damage induced by alterations in Top1p catalysis and the cellular processes that mediate the repair of such lesions, the yeastSaccharomyces cerevisiaewas used. Substitution of conserved residues N‐terminal to the active site tyrosine (Tyr‐727) produced alterations in the camptothecin sensitivity or catalytic cycle of DNA Top1. For example, substituting Ala for Thr‐722 in Top1T722A increased the stability of the covalent enzyme DNA intermediate. As with camptothecin, Top1T722A‐induced cytotoxicity was ascribed to a reduction in DNA religation. By contrast, enhanced covalent complex formation by Top1N726H resulted from a relative increase in the rate of DNA cleavage. Conditional yeast mutants were also selected that exhibit temperature‐sensitive growth only in the presence of the self‐poisoning Top1T722A enzyme. Subsequent analyses of thesetahmutants identified 9 genes whose function suppresses the cytotoxic action of camptothecin and Top1T722A. These include genes encoding essential DNA replication proteins (CDC45andDPB11) and proteins involved in SUMO‐ or ubiquitination (UBC9andDOA4).