bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statins inhibit the growth of variant human embryonic stem cells and cancer cells in vitro but not normal human embryonic stem cells
Authors: Gauthaman K , Manasi N , Bongso A 
Published: May 2009

Background and purpose:  Statins inhibit proliferation of various human cancer cell lines in vitro. As human embryonic stem cells (hESCs) possess neoplastic‐like properties we have evaluated the role of various statins on karyotypically normal hESCs (HES3 and BG01), abnormal hESCs (BG01V) and breast adenocarcinoma cells (MCF‐7) to evaluate whether the mode of action of the statins was via a stemness pathway.Experimental approach:  All cell lines were treated with simvastatin, pravastatin, lovastatin and mevastatin (1 µmol·L−1 to 20 µmol·L−1) up to 7 days and their effects on cell proliferation, cell cycle, apoptosis and pluripotency studied.Key results:  All four statins did not inhibit HES3 and BG01 proliferation, but BG01V and MCF‐7 were inhibited by simvastatin, lovastatin and mevastatin. These inhibitory effects were reversed by the endogenous isoprenoids, farnesylpyrophosphate and geranylgeranylpyrophosphate. Terminal deoxynucleotidyl transferase biotin‐dUTP nick end labelling and cell cycle assay confirmed apoptosis in BG01V and MCF‐7. Stem cell surface markers [stage‐specific embryonic antigen‐4, tumour rejection antigen‐1‐81, octamer‐4 (OCT‐4)] were expressed in HES3 and BG01, but not in BG01V cells, even after prolonged treatment with simvastatin. In BG01V and MCF‐7, the pro‐apoptotic Bcl‐2‐associated X protein genes were up‐regulated, while the antiapoptotic BCL2 and SURVIVIN genes were down‐regulated. Expression of the stemness‐related genes namely, the growth differentiation factor‐3, NANOG and OCT‐4 was decreased in BG01V compared with BG01 and HES3.Conclusions and implications:  Normal hESCs were resistant to prolonged exposure to statins over a range of doses, compared with BG01V and MCF‐7, probably because of genetic and behavioural differences. The statins not only have anti‐cancer properties but can suppress abnormal hESCs thus promoting growth of normal hESCs in vitro.
Reactive oxygen species up‐regulate p53 and Puma; a possible mechanism for apoptosis during combined treatment with TRAIL and wogonin
Authors: Lee Dae‐Hee , Rhee Juong G , Lee Yong J 
Published: May 2009

Background and purpose: Tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) triggers apoptotic death in a variety of cancer cells without marked toxicity to most normal cells. We previously reported that wogonin, a potent anticancer agent from a Chinese herb, up‐regulates p53 in prostate cancer cells. In this study, the effects of combinations of TRAIL and wogonin on a human prostate cancer cell line LNCaP, resistant to TRAIL, was evaluated for evidence of synergy in triggering apoptosis.Experimental approach: Western blot assay and the ‘comet’ assay were used to study the underlying mechanisms of cell death and search for any mechanisms of enhancement of TRAIL‐induced apoptosis in the presence of wogonin.Key results: During combined treatment with wogonin and TRAIL, cytotoxicity, poly(ADP‐ribose) polymerase cleavage and caspase activation were associated with up‐regulation of p53 through DNA damage and reactive oxygen species (ROS) generation. N‐acetylcysteine (NAC), an antioxidant, inhibited ROS generation and synergistic interaction between TRAIL and wogonin. Experimental results in human colon cancer HCT116 cells demonstrated that p53‐dependent Puma up‐regulation played an important role; deficiency in either p53 or Puma prevented wogonin‐enhanced TRAIL‐induced apoptosis.Conclusions and implications: The present studies suggest that wogonin enhances TRAIL‐induced cytotoxicity through up‐regulation of p53 and Puma, mediated by ROS.
Red blood cell alloimmunization among sickle cell Kuwaiti Arab patients who received red blood cell transfusion
Authors: Ameen Reem , Al Shemmari Salem , Al‐Bashir Abdulaziz 
Published: May 2009

BACKGROUND: Sickle cell disease (SCD) is common in the Arabian Gulf region. Most cases require a red blood cell (RBC) transfusion, increasing the potential for RBC alloantibody development. The incidence of RBC alloimmunization among Kuwaiti Arab SCD patients is not yet known. This study retrospectively assessed the effect of using two different matching protocols on the incidence of alloimmunization among multiply transfused Kuwaiti Arab SCD patients.STUDY DESIGN AND METHODS: A total of 233 Kuwaiti Arab SCD patients were divided into two groups: Group 1 (n = 110) received RBC transfusion through standard ABO‐ and D‐matched nonleukoreduced blood; Group 2 (n = 123) received RBCs matched for ABO, Rh, and K1 poststorage‐leukoreduced blood. Multivariate analysis was performed on the factors associated with RBC alloimmunization and antibody specificity.RESULTS: Sixty‐five percent of patients in Group 1 developed clinically significant RBC alloantibody with an increased prevalence in females; in patients in Group 2, 23.6% developed RBC alloantibodies (p = 0.01). In Group 1, 72 patients (65.5%) had alloantibodies directed against Rh and Kell systems (p = 0.01). Multivariate analysis further confirmed the results, showing that blood transfusion type and sex have significant effects on the rate of alloimmunizations.CONCLUSION: This study confirms the importance of selecting RBCs matched for Rh and Kell to reduce the risk of alloimmunizations among Kuwaiti Arab SCD patients.
Higher infused CD34+ hematopoietic stem cell dose correlates with earlier lymphocyte recovery and better clinical outcome after autologous stem cell transplantation in non‐Hodgkin's lymphoma
Authors: Yoon Dok Hyun , Sohn Byeong Seok , Jang Geundoo , Kim Eun Kyoung , Kang Byung Woog , Kim Chul , Kim Jeong‐Eun , Kim Shin , Lee Dae Ho , Lee Jung‐Shin , Park Seo‐Jin , Park Chan‐Jeoung , Huh Jooryung , Suh Cheolwon 
Published: May 2009

BACKGROUND: Lymphocyte recovery after autologous stem cell transplantation (ASCT) has been shown to be associated with positive clinical outcome in non‐Hodgkin's lymphoma (NHL). This study sought to identify variables that affect lymphocyte recovery and survival after ASCT.STUDY DESIGN AND METHODS: A retrospective analysis of outcomes in 97 consecutive patients with NHL who underwent ASCT in a single center from August 1999 to January 2008 was conducted.RESULTS: A significant relationship was not observed between infused lymphocyte count and days to recovery of absolute lymphocyte count 500 × 106/L or greater after ASCT (ALC500; r = 0.139, p = 0.176), but there was a significant inverse correlation between infused CD34+ cell count and days to ALC500 (r = −0.333, p = 0.001). Univariately, infused CD34+ cell count and recovery of ALC500 by 20th day after ASCT were significant predictors of survival. The median overall survival (OS) and event‐free survival (EFS) were significantly longer in patients who received 8.2 × 106 CD34+ cells/kg or more than in those who received fewer than 8.2 × 106 CD34+ cells/kg (OS, not reached vs. 11.6 months, p = 0.001; EFS, not reached vs. 4.8 months, p = 0.003). Multivariate analysis confirmed that infused CD34+ cell count was an independent prognostic factor for OS (p = 0.017) and EFS (p = 0.002).CONCLUSION: These data suggest that infused CD34+ cell count is predictive of kinetics of lymphocyte recovery after ASCT and is an independent prognostic factor for OS and EFS after ASCT in patients with NHL.
Evaluation of low red blood cell mean corpuscular volume in an apheresis donor population
Authors: Bryant Barbara J. , Hopkins Julie A. , Arceo Sarah M. , Leitman Susan F. 
Published: May 2009

BACKGROUND: Apheresis donors are routinely evaluated with a complete blood count (CBC). Low red blood cell mean corpuscular volume (MCV) values (<80 fL) in the presence of an acceptable hemoglobin (Hb; ≥12.5 g/dL) could be due to iron deficiency or hemoglobinopathy. The etiology of a low MCV in a healthy apheresis donor population was assessed.METHODS: Predonation samples for CBC were obtained from 1162 consecutive apheresis donors. Donors with a MCV of less than 80 fL were evaluated by CBC, iron studies (ferritin, serum iron, transferrin, percentage of transferrin saturation), and hemoglobin (Hb) electrophoresis. Iron deficiency was defined as a ferritin value below the reference range. Beta chain Hb variants were determined by Hb electrophoresis. Alpha thalassemia trait was presumed if the red blood cell (RBC) count was elevated, no variant Hbs were detected, and the iron studies were within normal ranges.RESULTS: In a 19‐month period, 33 of 1162 apheresis donors had low MCV values. Iron deficiency was present in 64%; 49% had isolated iron deficiency and 15% had iron deficiency plus hemoglobinopathy. Hemoglobinopathy without concomitant iron deficiency was found in the remaining 36%.CONCLUSION: Iron deficiency is present in the majority of apheresis donors with repeatedly low MCV values and Hb levels of 12.5 g/dL or more. Hemoglobinopathy is also commonly present but may not be easily recognized in the setting of iron deficiency. The MCV is a useful screening tool to detect iron deficiency and hemoglobinopathy. Low MCV values should be investigated to determine if iron replacement therapy is indicated.
Association between duration of storage of transfused red blood cells and morbidity and mortality in adult patients: myth or reality?
Authors: Lelubre Christophe , Piagnerelli Michael , Vincent Jean‐Louis 
Published: May 2009

BACKGROUND: The duration of red blood cell (RBC) storage before transfusion may alter RBC function and, therefore, influence the incidence of complications.STUDY DESIGN AND METHODS: With a computerized literature search from 1983 to 2008, 27 studies reporting the relationship between age of transfused RBCs and physiologic variables or incidence of complications in adult patients were identified.RESULTS: Three studies (one abstract only, two foreign language) were excluded. The 24 remaining studies were grouped according to the patient population: cardiac surgery (eight studies), colorectal surgery (three), intensive care unit (ICU; seven), and trauma (six). The studies were too heterogeneous to allow a formal meta‐analysis. Twenty‐one of the 24 studies were single‐center, and 12 were retrospective. The number of patients was highly variable, ranging from 15 to 6002. In cardiac surgery, two studies reported an increased risk of mortality but had statistical limitations. In colorectal surgery, two studies that addressed the effect on postoperative infections in the same database but with different designs yielded conflicting results. In general ICU patients, two retrospective studies reported a significant correlation between length of RBC storage and microcirculatory alterations or mortality, but the results were not confirmed in subsequent prospective, double‐blinded studies. In trauma, five studies reported a correlation between RBC age and development of infection, multiple organ dysfunction, or mortality.CONCLUSIONS: From the currently available published data, it is difficult to determine whether there is a relationship between the age of transfused RBCs and outcome in adult patients, except possibly in trauma patients receiving massive transfusion.
Emergency Department Patient Flow: The Influence of Hospital Census Variables on Emergency Department Length of Stay
Authors: Lucas Ray , Farley Heather , Twanmoh Joseph , Urumov Andrej , Olsen Nils , Evans Bruce , Kabiri Hamed 
Published: May 2009

AbstractObjectives:  The objective was to evaluate the association between hospital census variables and emergency department (ED) length of stay (LOS). This may give insights into future strategies to relieve ED crowding.Methods:  This multicenter cohort study captured ED LOS and disposition for all ED patients in five hospitals during five 1‐week study periods. A stepwise multiple regression analysis was used to examine associations between ED LOS and various hospital census parameters.Results:  Data were analyzed on 27,325 patients on 161 study days. A significant positive relationship was demonstrated between median ED LOS and intensive care unit (ICU) census, cardiac telemetry census, and the percentage of ED patients admitted each day. There was no relationship in this cohort between ED LOS and ED volume, total hospital occupancy rate, or the number of scheduled cardiac or surgical procedures.Conclusions:  In multiple hospital settings, ED LOS is correlated with the number of admissions and census of the higher acuity nursing units, more so than the number of ED patients each day, particularly in larger hospitals with busier EDs. Streamlining ED admissions and improving availability of inpatient critical care beds may reduce ED LOS.
Paramedic and Emergency Medical Technicians Views on Opportunities and Challenges When Forgoing and Halting Resuscitation in the Field
Authors: Grudzen Corita R. , Timmermans Stefan , Koenig William J. , Torres Jacqueline M. , Hoffman Jerome R. , Lorenz Karl A. , Asch Steven M. 
Published: May 2009

AbstractObjectives:  The objective was to assess paramedic and emergency medical technicians (EMT) perspectives and decision‐making after a policy change that allows forgoing or halting resuscitation in prehospital atraumatic cardiac arrest.Methods:  Five semistructured focus groups were conducted with 34 paramedics and 2 EMTs from emergency medical services (EMS) agencies within Los Angeles County (LAC), 6 months after a policy change that allowed paramedics to forgo or halt resuscitation in the field under certain circumstances.Results:  Participants had an overwhelmingly positive view of the policy; felt it empowered their decision‐making abilities; and thought the benefits to patients, family, EMS, and the public outweighed the risks. Except under certain circumstances, such as when the body was in public view or when family members did not appear emotionally prepared to have the body left on scene, they felt the policy improved care. Assuming that certain patient characteristics were present, decisions by paramedics about implementing the policy in the field involve many factors, including knowledge and comfort with the new policy, family characteristics (e.g., agreement), and logistics regarding the place of arrest (e.g., size of space). Paramedic and EMT experiences with and attitudes toward forgoing resuscitation, as well as group dynamics among EMS leadership, providers, police, and ED staff, also play a role.Conclusions:  Participants view the ability to forgo or halt resuscitation in the field as empowering and do not believe it presents harm to patients or families under most circumstances. Factors other than patient clinical characteristics, such as knowledge and attitudes toward the policy, family emotional preparedness, and location of arrest, affect whether paramedics will implement it.
Hepatoma‐derived growth factor and its role in keloid pathogenesis
Authors: Ooi B.N.S. , Mukhopadhyay A. , Masilamani J. , Do D.V. , Lim C.P. , Cao X.M. , Lim I.J. , Mao L. , Ren H.N. , Nakamura H. , Phan T.T. 
Published: May 2009

AbstractHepatoma‐derived growth factor (HDGF) is a novel mitogenic growth factor that has been implicated in many different carcinomas. Its role in keloid biology has not yet been investigated. The present study is aimed at examining the role of HDGF in keloid pathogenesis. Immunohistochemical staining and Western blot analyses were used to examine in vivo localization and expression of HDGF in keloid and normal skin tissue. This was followed by the detection of HDGF expression in fibroblasts cultured in vitro and fibroblasts exposed to serum. To investigate the effect of epithelial–mesenchymal interactions, a two‐chamber system was employed in which keratinocytes on membrane inserts were co‐cultured with the fibroblasts. HDGF expression levels in all cell extracts and conditioned media were assayed through Western blot analysis. In another set of experiments, the effect of exogenous recombinant HDGF on keloid fibroblasts (KF) and normal fibroblasts (NF) was examined. Cell proliferation was assessed by the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay and by quantifying proliferating cell nuclear antigen (PCNA) expression. Downstream targets of HDGF were identified by detecting their expression through Western blot analysis. Our results indicate that there was an increase in HDGF expression in the dermis of keloid compared with normal skin tissue. The application of serum and epithelial–mesenchymal interactions did not seem to have any effect on intracellular HDGF expression levels. However, co‐culturing keloid keratinocytes with KFs resulted in increased HDGF secretion when compared with monoculture or normal controls. Furthermore, treatment with exogenous recombinant HDGF was found to increase the proliferation of KFs, activate the extracellular signal‐regulated kinase (ERK) pathway and up‐regulate the secretion of vascular endothelial growth factor (VEGF).
Targeting a unique EGFR epitope with monoclonal antibody 806 activates NF‐κB and initiates tumour vascular normalization
Authors: Gan Hui K. , Lappas Martha , Cao Diana X. , Cvrljevdic Anna , Scott Andrew M. , Johns Terrance G. 
Published: May 2009

AbstractMonoclonal antibodies (mAbs) and tyrosine kinase inhibitors targeting the epidermal growth factor receptor (EGFR), which is often pathogenetically overexpressed or mutated in epithelial malignancies and glioma, have been modestly successful, with some approved for human use. MAb 806 was raised against de2–7EGFR (or EGFRvIII), a constitutively active mutation expressed in gliomas, but also recognizes a subset (<10%) of wild‐type (wt) EGFR when it is activated by autocrine loop, overexpression or mutation. It does not bind inactive EGFR in normal tissues like liver. Glioma xenografts expressing the de2–7EGFR treated with mAb 806 show reduced receptor autophosphorylation, increased p27KIP1 and reduced cell proliferation. Xenografts expressing the wtEGFR activated by overexpression or autocrine ligand are also inhibited by mAb 806, but the mechanism of inhibition has been difficult to elucidate, especially because mAb 806 does not prevent wtEGFR phosphorylation or downstream signalling in vitro. Thus, we examined the effects of mAb 806 on A431 xenograft angiogenesis. MAb 806 increases vascular endothelial growth factor (VEGF) and interleukin‐8 production by activating NF‐κB and normalizes tumour vasculature. Pharmacological inhibition of NF‐κB completely abrogated mAb 806 activity, demonstrating that NF‐κB activation is necessary for its anti‐tumour function in xenografts. Given the increase in VEGF, we combined mAb 806 with bevacizumab in vivo, resulting in additive activity.
CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver
Authors: Bourd‐Boittin Katia , Basset Laetitia , Bonnier Dominique , L’Helgoualc’h Annie , Samson Michel , Théret Nathalie 
Published: May 2009

AbstractChemokines are the inflammatory mediators that modulate liver fibrosis, a common feature of chronic inflammatory liver diseases. CX3CL1/fractalkine is a membrane‐associated chemokine that requires step processing for chemotactic activity and has been recently implicated in liver disease. Here, we investigated the potential shedding activities involved in the release of the soluble chemotactic peptides from CX3CL1 in the injured liver. We showed an increased expression of the sheddases ADAM10 and ADAM17 in patients with chronic liver diseases that was associated with the severity of liver fibrosis. We demonstrated that hepatic stellate cells (HSC) were an important source of ADAM10 and ADAM17 and that treatment with the inflammatory cytokine inter‐feron‐γ induced the expression of CX3CL1 and release of soluble peptides. This release was inhibited by the metalloproteinase inhibitor batimastat; however, ADAM10/ADAM17 inhibitor GW280264X only partially affected shedding activity. By using selective tissue metalloprotease inhibitors and overexpression analyses, we showed that CX3CL1 was mainly processed by matrix metalloproteinase (MMP)‐2, a metalloprotease highly expressed by HSC. We further demonstrated that the CX3CL1 soluble peptides released from stimulated HSC induced the activation of the CX3CR1‐dependent signalling pathway and promoted chemoattraction of monocytes in vitro. We conclude that ADAM10, ADAM17 and MMP‐2 synthesized by activated HSC mediate CX3CL1 shedding and release of chemotactic peptides, thereby facilitating recruitment of inflammatory cells and paracrine stimulation of HSC in chronic liver diseases.
Gingivitis as a risk factor in periodontal disease
Authors: Lang Niklaus P. , Schätzle Marc A. , Löe Harald 
Published: May 2009

AbstractBackground: Dental plaque has been proven to initiate and promote gingival inflammation. Histologically, various stages of gingivitis may be characterized prior to progression of a lesion to periodontitis. Clinically, gingivitis is well recognized.Material & Methods: Longitudinal studies on a patient cohort of 565 middle class Norwegian males have been performed over a 26‐year period to reveal the natural history of initial periodontitis in dental‐minded subjects between 16 and 34 years of age at the beginning of the study.Results: Sites with consistent bleeding (GI=2) had 70% more attachment loss than sites that were consistenly non‐inflamed (GI=0). Teeth with sites that were consistently non‐inflamed had a 50‐year survival rate of 99.5%, while teeth with consistently inflamed gingivae yielded a 50‐year survival rate of 63.4%.Conclusion: Based on this longitudinal study on the natural history of periodontitis in a dentally well‐maintained male population it can be concluded that persistent gingivitis represents a risk factor for periodontal attachment loss and for tooth loss.
Force–frequency and force–length properties in skeletal muscle following unilateral focal ischaemic insult in a rat model
Authors: Dormer G. N. , Teskey G. C. , MacIntosh B. R. 
Published: May 2009

AbstractAim:  Our purpose was to quantify skeletal muscle properties following unilateral focal ischaemic insult (stroke) in a rat model.Methods:  Male rats were divided into two groups: stroke and 2 weeks recovery (n = 8) and control group (n = 7). Stroke was induced in the area of the motor neocortex containing hind limb corticospinal neurones. Contractile properties of the medial gastrocnemius muscle were measured in situ in both limbs. Force–length and force–frequency properties were measured before and 35 min after 5 min fatiguing stimulation.Results:  Stroke resulted in bilateral tetanic fade during 200 Hz stimulation. When normalized to 100 Hz contractions, force at 200 Hz was 95.4 ± 0.9% for the paretic muscles, 96.7 ± 1.7% for non‐paretic muscles and 102.2 ± 1.0% for muscles of control rats (P = 0.006). Prior to fatiguing contractions, there was no difference in the length dependence of force. During repetitive contractions, active force fell significantly to 19 ± 4 and 25 ± 5% of initial force in paretic and non‐paretic muscles of animals with a stroke respectively. In control animals active force fell to 37 ± 5%. During repetitive contractions, fusion index increased in muscles of stroke animals to 1.0 ± 0 but in control animals it was 0.95 ± 0.02. There was selective force depression at short lengths for fatigued paretic muscle (significant difference at muscle lengths less than reference length −2 mm).Conclusion:  The tetanic fade at high stimulation frequencies indicates that there may be activation failure following focal ischaemic insult. The greater magnitude of fatigue and selective depression at short lengths following repetitive contractions should be investigated further.