bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
Pityriasis rubra pilaris – a retrospective single center analysis over eight years
Authors: Gemmeke Astrid , Schönlebe Jaqueline , Koch André , Wollina Uwe 
Published: July 2010

Summary 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

ABSTRACTThis 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

ABSTRACTSystems 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

ABSTRACTIn 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.
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

AbstractAim:  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

AbstractChromaffin 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

ABSTRACTMost 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.
Telomere Length Dynamics in Normal Individuals and in Patients with Hematopoietic Stem Cell‐Associated Disorders
Authors: BRÜMMENDORF TIM H. , RUFER NATHALIE , HOLYOAKE TESSA L. , MACIEJEWSKI JAREK , BARNETT MICHAEL J. , EAVES CONNIE J. , EAVES ALLEN C. , YOUNG NEAL , LANSDORP PETER M. 
Published: July 2010

Abstract: The telomere length in nucleated peripheral blood (PB) cells indirectly reflects the mitotic history of their precursors: the hematopoietic stem cells (HSCs). The average length of telomeres in PB leukocytes can be measured using fluorescence in situ hybridization and flow cytometry (flow FISH). We previously used flow FISH to characterize the age‐related turnover of HSCs in healthy individuals. In this review, we describe results of recent flow FISH studies in patients with selected hematopoietic stem cell‐associated disorders: chronic myelogeneous leukemia (CML) and several bone marrow failure syndromes.CML is characterized by a marked expansion of myeloid Philadelphia chromosome positive (Ph+) cells. Nevertheless, nonmalignant (Ph−) HSCs typically coexist in the bone marrow of CML patients. We analyzed the telomere length in >150 peripheral blood leukocytes (PBLs) and bone marrow samples of patients with CML as well as samples of Ph‐ T‐lymphocytes. Compared to normal controls, the overall telomere fluorescence in PBLs of patients with CML was significantly reduced. However, no telomere shortening was observed in Ph‐ T‐lymphocytes. Patients in late chronic phase (CP) had significantly shorter telomeres than those assessed earlier in CP. Our data suggest that progressive telomere shortening is correlated with disease progression in CML.Within the group of patients with bone marrow failure syndromes, we only found significantly shortened telomeres (compared to age‐adjusted controls) in granulocytes from patients with aplastic anemia (AA). Strikingly, the telomere length in granulocytes from AA patients who had recovered after immunosuppressive therapy (recAA) did not differ significantly from controls, whereas untreated patients and nonresponders with persistent severe pancytopenia (sAANR) showed marked and significant telomere shortening compared to healthy donors and patients with recAA. Furthermore, an inverse correlation between age‐adjusted telomere length and peripheral blood counts was found in support of a model in which the degree of cytopenia and the amount of telomere shortening are correlated. These results support the concept of extensive proliferation of HSCs in subgroups of AA patients and suggest a potential use of telomere‐length measurements as a prognostic tool in this group of disorders as well.
Laparoscopic Management of Adnexal Masses
Authors: PEJOVIC TANJA , NEZHAT FARR 
Published: July 2010

AbstractSuspected ovarian neoplasm is a common clinical problem affecting women of all ages. Although the majority of adnexal masses are benign, the primary goal of diagnostic evaluation is the exclusion of malignancy. It has been estimated that approximately 5–10% of women in the United States will undergo a surgical procedure for a suspected ovarian neoplasm during their lifetime. Despite the magnitude of the problem, there is still considerable disagreement regarding the optimal surgical management of these lesions. Traditional management has relied on laparotomy to avoid undertreatment of a potentially malignant process. Advances in detection, diagnosis, and minimally invasive surgical techniques make it necessary now to review this practice in an effort to avoid unnecessary morbidity among patients. Here, we review the literature on the laparosopic approach to the treatment of the adnexal mass without sacrificing the principles of oncologic surgery. We highlight potentials of minimally invasive surgery and address the risks associated with the laparoscopic approach.
Toward Mechanism‐based Antioxidant Interventions
Authors: KAGAN VALERIAN E. , KISIN ELENA R. , KAWAI KAZUAKI , SERINKAN BEHICE F. , OSIPOV ANATOLY N. , SERBINOVA ELENA A. , WOLINSKY IRA , SHVEDOVA ANNA A. 
Published: July 2010

AbstractIt is generally accepted that one of the major and important contributions to skin aging, skin disorders, and skin diseases results from reactive oxygen species. More than other tissues, the skin is exposed to numerous environmental chemical and physical agents, such as ultraviolet light, causing oxidative stress. Accelerated cutaneous UV‐induced aging, photo aging, is only one of the harmful effects of continual oxygen radical production in the skin. Interestingly, our ELISA assays of 8‐oxo‐2′‐deoxyguanosine in skin of young and old Balb/c mice showed that cumene hydroperoxide‐induced accumulation of the biomarker of oxidative DNA damage in skin of 32‐week‐old mice occurred independently of their vitamin E status, while no accumultaion of oxo8‐dG was detectable in the skin of young animals. This suggests that vitamin E is not the major protector of skin against cumene hydroperoxide‐induced oxidative stress. Production and accumulation of apoptotic cells is one of the characteristic features of skin damage by oxidative stress that, in the absence of effective scavenging by macrophages, dramatically enhances oxidative damage and inflammatory response. In our model experiments, we demonstrated that Cu‐OOH induces significant oxidative stress in phospholipids of normal human epidermal keratinocytes (NHEK) whose characteristic feature is an early and profound oxidation of phosphatidylserine (PS), likely related to PS externalization. Since externalized PS is a signal for recognition of apoptotic cells by macrophage scavenger receptors, PS oxidation may be translatable into elimination of thus damaged NHEKs. Experiments are now underway to determine whether inhibition of PS oxidation by antioxidants may interfere with improtant signaling functions of oxidative stress in eliminating apoptotic cells.
Cognitive Impairment of Rats Caused by Oxidative Stress and Aging, and Its Prevention by Vitamin E
Authors: FUKUI KOJI , OMOI NAO‐OMI , HAYASAKA TAKAHIRO , SHINNKAI TADASHI , SUZUKI SHOZO , ABE KOUICHI , URANO SHIRO 
Published: July 2010

AbstractIn order to verify whether brain damage caused by chronic oxidative stress induces the impairment of cognitive function, the ability of learning and memory was assessed using the water maze and the eight‐arm radial maze tasks. Young rats showed significantly greater learning ability before the stress than the old and vitamin E‐deficient rats. At five days after subjection to oxidative stress, the memory function of the young declined toward the level of that in the aged rats maintained under normal condition. This phenomenon is supported by the findings that the delayed‐type apoptosis appeared in the CA1 region of the hippocampus of the young at five to seven days after the stress. Vitamin E supplementation to the young accelerated significantly their learning functions before the stress and prevented the deficit of memory caused by the stress. When rats were subjected to stress, thiobarbituric acid‐reactive substance (TBARS), lipid hydroperoxides, and protein carbonyls were significantly increased in synaptic plasma membranes. It was found that ζ‐potential of the synaptic membrane surface was remarkably decreased. These phenomena were also observed in the aged and vitamin E‐deficient rats maintained under normal condition. These results suggest that oxidative damage to the rat synapse in the cerebral cortex and hippocampus during aging may contribute to the deficit of cognitive functions.
A Unified Mechanism in the Initiation of Cancer
Authors: CAVALIERI ERCOLE L. , ROGAN ELEANOR G. 
Published: July 2010

AbstractEstrogens are involved in the initiation of breast, prostate, and other kinds of human cancer. In this process, the endogenous estrogens, estrone and estradiol, are metabolized to 2‐catechol estrogens (2‐CE, major) and 4‐CE (minor). If the 4‐CEs are further oxidized to CE‐3,4‐quinones, they may react with DNA to form depurinating adducts at N‐7 of guanine and N‐3 of adenine, and generate apurinic sites. Similarly, the carcinogenic synthetic estrogen hexestrol, a hydrogenated derivative of diethylstilbestrol, is metabolized to its quinone, which reacts with DNA to form analogous depurinating adducts. This could be the primary critical event leading to oncogenic mutations and then initiation of cancer. Evidence supporting this hypothesis has been obtained from the human breast and animal models susceptible to estrogen‐induced tumors, including the Syrian golden hamster kidney, ACI rat mammary gland, and Noble rat prostate. The oxidation of phenols to catechols and then to quinones is not only a mechanism of tumor initiation for natural and synthetic estrogens, but also for the leukemogen benzene. In fact, catechol, one of the metabolites of benzene, when oxidized to its quinone, reacts with DNA to form N7guanine and N3adenine depurinating adducts. Thus, a unifying mechanism, namely formation of catechol quinones and reaction with DNA, could initiate not only cancer by oxidation of specific endogenous estrogen metabolites, but also leukemia by oxidation of benzene.