bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll‐like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring
Authors: Wang JianFei , Hori Keijiro , Ding Jie , Huang Yue , Kwan Peter , Ladak Adil , Tredget Edward E. 
Published: October 2010

AbstractHypertrophic scar (HTS), a fibroproliferative disorder (FPD), complicates burn wound healing. Although the pathogenesis is not understood, prolonged inflammation is a known contributing factor. Emerging evidence suggests that fibroblasts regulate immune/inflammatory responses through toll‐like receptor 4 (TLR4) activated by lipopolysaccharide (LPS) through adaptor molecules, leading to nuclear factor kappa‐light‐chain‐enhancer of activated B cells and mitogen‐activated protein kinases activation, cytokine gene transcription and co‐stimulatory molecule expression resulting in inflammation. This study explored the possible role of TLR4 in HTS formation. Paired normal and HTS tissue from burn patients was collected and dermal fibroblasts isolated and cultured. Immunohistochemical analysis of tissues demonstrated increased TLR4 staining in HTS tissue. Quantitative RT‐PCR of three pairs of fibroblasts demonstrated mRNA levels for TLR4 and its legend myeloid differentiation factor 88 (MyD88) in HTS fibroblasts were increased significantly compared with normal fibroblasts. Flow cytometry showed increased TLR4 expression in HTS fibroblasts compared with normal. ELISA demonstrated protein levels for prostaglandin E2, interleukin (IL)‐6, IL‐8 and monocyte chemotactic protein‐1 (MCP‐1) were significantly increased in HTS fibroblasts compared to normal. When paired normal and HTS fibroblasts were stimulated with LPS, significant increases in mRNA and protein levels for MyD88, IL‐6, IL‐8, and MCP‐1 were detected. However, when transfected with MyD88 small interfering RNA (siRNA), then stimulated with LPS, a significant decrease in mRNA and protein levels for these molecules compared to only LPS‐stimulated fibroblasts was detected. In comparison, a scramble siRNA transfection did not affect mRNA or protein levels for these molecules. Results demonstrate LPS stimulates proinflammatory cytokine expression in dermal fibroblasts and MyD88 siRNA eliminates the expression. Therefore, controlling inflammation and manipulating TLR signaling in skin cells may result in novel treatment strategies for HTS and other FPD. J. Cell. Physiol. 226: 1265–1273, 2011. © 2010 Wiley‐Liss, Inc.
Protein kinase Cι expression and oncogenic signaling mechanisms in cancer
Authors: Murray Nicole R. , Kalari Krishna R. , Fields Alan P. 
Published: October 2010

AbstractAccumulating evidence demonstrates that PKCι is an oncogene and prognostic marker that is frequently targeted for genetic alteration in many major forms of human cancer. Functional data demonstrate that PKCι is required for the transformed phenotype of lung, pancreatic, ovarian, prostate, colon, and brain cancer cells. Future studies will be required to determine whether PKCι is also an oncogene in the many other cancer types that also overexpress PKCι. Studies of PKCι using genetically defined models of tumorigenesis have revealed a critical role for PKCι in multiple stages of tumorigenesis, including tumor initiation, progression, and metastasis. Recent studies in a genetic model of lung adenocarcinoma suggest a role for PKCι in transformation of lung cancer stem cells. These studies have important implications for the therapeutic use of aurothiomalate (ATM), a highly selective PKCι signaling inhibitor currently undergoing clinical evaluation. Significant progress has been made in determining the molecular mechanisms by which PKCι drives the transformed phenotype, particularly the central role played by the oncogenic PKCι‐Par6 complex in transformed growth and invasion, and of several PKCι‐dependent survival pathways in chemo‐resistance. Future studies will be required to determine the composition and dynamics of the PKCι‐Par6 complex, and the mechanisms by which oncogenic signaling through this complex is regulated. Likewise, a better understanding of the critical downstream effectors of PKCι in various human tumor types holds promise for identifying novel prognostic and surrogate markers of oncogenic PKCι activity that may be clinically useful in ongoing clinical trials of ATM. J. Cell. Physiol. 226: 879–887, 2011. © 2010 Wiley‐Liss, Inc.
Live cell imaging of the cancer‐related transcription factor RUNX2 during mitotic progression
Authors: Pockwinse Shirwin M. , Kota Krishna P. , Quaresma Alexandre J.C. , Imbalzano Anthony N. , Lian Jane B. , van Wijnen Andre J. , Stein Janet L. , Stein Gary S. , Nickerson Jeffrey A. 
Published: October 2010

AbstractThe nuclear matrix bound transcription factor RUNX2 is a lineage‐specific developmental regulator that is linked to cancer. We have previously shown that RUNX2 controls transcription of both RNA polymerase II genes and RNA polymerase I‐dependent ribosomal RNA genes. RUNX2 is epigenetically retained through mitosis on both classes of target genes in condensed chromosomes. We have used fluorescence recovery after photobleaching to measure the relative binding kinetics of enhanced green fluorescent protein (EGFP)‐RUNX2 at transcription sites in the nucleus and nucleoli during interphase, as well as on mitotic chromosomes. RUNX2 becomes more strongly bound as cells go from interphase through prophase, with a doubling of the most tightly bound “immobile fraction.” RUNX2 exchange then becomes much more facile during metaphase to telophase. During interphase the less tightly bound pool of RUNX2 exchanges more slowly at nucleoli than at subnuclear foci, and the non‐exchanging immobile fraction is greater in nucleoli. These results are consistent with a model in which the molecular mechanism of RUNX2 binding is different at protein‐coding and ribosomal RNA genes. The binding interactions of RUNX2 change as cells go through mitosis, with binding affinity increasing as chromosomes condense and then decreasing through subsequent mitotic phases. The increased binding affinity of RUNX2 at mitotic chromosomes may reflect its epigenetic function in “bookmarking” of target genes in cancer cells. J. Cell. Physiol. 226: 1383–1389, 2011. © 2010 Wiley‐Liss, Inc.
5‐hydroxy‐2‐(4‐hydroxy‐3‐methoxyphenyl)‐3,7‐dimethoxy‐4H‐chromen‐4‐one (MSF‐2) suppresses fMLP‐mediated respiratory burst in human neutrophils by inhibiting phosphatidylinositol 3‐kinase activity
Authors: Liao Chang‐Hui , Chen Jih‐Jung , Lin Jieru Egeria , Liu Chia‐Hsin , Tseng Ching‐Ping , Day Yuan‐Ji 
Published: October 2010

AbstractRespiratory burst mediates crucial bactericidal mechanism in neutrophils. However, undesirable respiratory burst leads to pathological inflammation and tissue damage. This study investigates the effect and the underlying mechanism of 5‐hydroxy‐2‐(4‐hydroxy‐3‐methoxyphenyl)‐3,7‐dimethoxy‐4H‐chromen‐4‐one (MSF‐2), a lignan extracted from the fruit of Melicope Semecarprifolia, on fMLP‐induced respiratory burst in human neutrophils and suggests a possible therapeutic approach to ameliorate disease associated with neutrophil hyperactivation. MSF‐2 inhibited fMLP‐induced neutrophil superoxide anion production, cathepsin G release and migration in human neutrophils isolated from healthy volunteers, reflecting inhibition of phosphatidylinositol 3‐kinase (PI3K) activation. Specifically, PI3K/AKT activation results in migration, degranulation and superoxide anion production in neutrophils. MSF‐2 suppresses PI3K activation and phosphatidylinositol (3,4,5)‐trisphosphate (PIP3) production, and consequently inhibits downstream activation of PDK1 and AKT. Further, PI3K also stimulates respiratory burst via PLC‐dependent elevation of intracellular calcium. MSF‐2 reduces fMLP‐mediated PLCγ2 activation and intracellular calcium accumulation notably through extracellular calcium influx in a PI3K and PLC‐dependent manner. However, MSF‐2 is not a competitive or allosteric antagonist of fMLP. Additionally, in an in vivo study, MSF‐2 prevents fMLP‐induced neutrophil infiltration and inflammation in mice. In conclusion, MSF‐2 opposes fMLP‐mediated neutrophil activation and inflammation by inhibiting PI3K activation and subsequent activation of AKT and PLCγ2. J. Cell. Physiol. 226: 1519–1530, 2011. © 2010 Wiley‐Liss, Inc.
FTS (fused toes homolog) a novel oncoprotein involved in uterine cervical carcinogenesis and a potential diagnostic marker for cervical cancer
Authors: Cinghu Senthilkumar , Anandharaj Arunkumar , Lee Ho‐chang , Yu Jae‐Ran , Park Woo‐Yoon 
Published: October 2010

AbstractThe high incidence and fatality rate of uterine cervical cancer warrant effective diagnostic and therapeutic target identification for this disease. Here, we have found a novel oncoprotein FTS (Fused Toes Homolog), which is involved in cervical cancer pathogenesis. Immnohistochemical analysis of human cervical biopsy samples revealed that the expression of FTS is absent in normal cervical epithelium but progressively overexpressed in human cervical intraneoplastic lesions (CIN‐I to CIN‐III), this characteristic phenomenon put this protein, a potential diagnostic marker for the screening of early neoplastic changes of cervix. Using FTS‐specific small hairpin RNA (shRNA) in cervical cancer cells, we determined a specific role for FTS protein in, cervical neoplasia. Targeted stable knock down of FTS in HeLa cells led to the growth inhibition, cell‐cycle arrest, and apoptosis with concurrent increase in p21 protein. FTS effectively represses the p21 mRNA expression in dual luciferase assay which indicates that p21 is transcriptionally regulated by this oncoprotein which in turn affect the regular cell‐cycle process and its components. Consistent with this we found a reciprocal association between these proteins in early cervical neoplastic tissues. These data unraveled the involvement of new oncoprotein FTS in cervical cancer which plays a central role in carcinogenesis. Targeted inhibition of FTS lead to the shutdown of key elemental characteristics of cervical cancer and could lead to an effective therapeutic strategy for cervical cancer. J. Cell. Physiol. 226: 1564–1572, 2011. © 2010 Wiley‐Liss, Inc.
The role of electrical signals in murine corneal wound re‐epithelialization
Authors: Kucerova Romana , Walczysko Petr , Reid Brian , Ou Jingxing , Leiper Lucy J. , Rajnicek Ann M. , McCaig Colin D. , Zhao Min , Collinson J Martin 
Published: October 2010

AbstractIon flow from intact tissue into epithelial wound sites results in lateral electric currents that may represent a major driver of wound healing cell migration. Use of applied electric fields (EF) to promote wound healing is the basis of Medicare‐approved electric stimulation therapy. This study investigated the roles for EFs in wound re‐epithelialization, using the Pax6+/− mouse model of the human ocular surface abnormality aniridic keratopathy (in which wound healing and corneal epithelial cell migration are disrupted). Both wild‐type (WT) and Pax6+/− corneal epithelial cells showed increased migration speeds in response to applied EFs in vitro. However, only Pax6+/+ cells demonstrated consistent directional galvanotaxis towards the cathode, with activation of pSrc signaling, polarized to the leading edges of cells. In vivo, the epithelial wound site normally represents a cathode, but 43% of Pax6+/− corneas exhibited reversed endogenous wound‐induced currents (the wound was an anode). These corneas healed at the same rate as WT. Surprisingly, epithelial migration did not correlate with direction or magnitude of endogenous currents for WT or mutant corneas. Furthermore, during healing in vivo, no polarization of pSrc was observed. We found little evidence that Src‐dependent mechanisms of cell migration, observed in response to applied EFs in vitro, normally exist in vivo. It is concluded that endogenous EFs do not drive long‐term directionality of sustained healing migration in this mouse corneal epithelial model. Ion flow from wounds may nevertheless represent an important component of wound signaling initiation. J. Cell. Physiol. 226: 1544–1553, 2011. © 2010 Wiley‐Liss, Inc.
Potential role of follicle‐stimulating hormone (FSH) and transforming growth factor (TGFβ1) in the regulation of ovarian angiogenesis
Authors: Kuo Shih‐Wei , Ke Ferng‐Chun , Chang Geen‐Dong , Lee Ming‐Ting , Hwang Jiuan‐Jiuan 
Published: October 2010

AbstractAngiogenesis occurs during ovarian follicle development and luteinization. Pituitary secreted FSH was reported to stimulate the expression of endothelial mitogen VEGF in granulosa cells. And, intraovarian cytokine transforming growth factor (TGF)β1 is known to facilitate FSH‐induced differentiation of ovarian granulosa cells. This intrigues us to investigate the potential role of FSH and TGFβ1 regulation of granulosa cell function in relation to ovarian angiogenesis. Granulosa cells were isolated from gonadotropin‐primed immature rats and treated once with FSH and/or TGFβ1 for 48 h, and the angiogenic potential of conditioned media (granulosa cell culture conditioned media; GCCM) was determined using an in vitro assay with aortic ring embedded in collagen gel and immunoblotting. FSH and TGFβ1 increased the secreted angiogenic activity in granulosa cells (FSH + TGFβ1 > FSH ≈ TGFβ1 > control) that was partly attributed to the increased secretion of pro‐angiogenic factors VEGF and PDGF‐B. This is further supported by the evidence that pre‐treatment with inhibitor of VEGF receptor‐2 (Ki8751) or PDGF receptor (AG1296) throughout or only during the first 2‐day aortic ring culture period suppressed microvessel growth in GCCM‐treated groups, and also inhibited the FSH + TGFβ1‐GCCM‐stimulated release of matrix remodeling‐associated gelatinase activities. Interestingly, pre‐treatment of AG1296 at late stage suppressed GCCM‐induced microvessel growth and stability with demise of endothelial and mural cells. Together, we provide original findings that both FSH and TGFβ1 increased the secretion of VEGF and PDGF‐B, and that in turn up‐regulated the angiogenic activity in rat ovarian granulosa cells. This implicates that FSH and TGFβ1 play important roles in regulation of ovarian angiogenesis during follicle development. J. Cell. Physiol. 226: 1608–1619, 2011. © 2010 Wiley‐Liss, Inc.
Involvement of membrane type 1‐matrix metalloproteinase (MT1‐MMP) in RAGE activation signaling pathways
Authors: Kamioka Masashi , Ishibashi Toshiyuki , Ohkawara Hiroshi , Nagai Ryoji , Sugimoto Koichi , Uekita Hironori , Matsui Takanori , Yamagishi Sho‐Ichi , Ando Katsuya , Sakamoto Takayuki , Sakamoto Nobuo , Takuwa Yoh , Wada Ikuo , Shiomi Masashi , Maruyama Yukio , Takeishi Yasuchika 
Published: October 2010

AbstractAn advanced glycation end products (AGE)/a receptor for AGE (RAGE) axis plays a key role in diabetic vascular complications. Membrane type 1‐matrix metalloproteinase (MT1‐MMP) has been shown to function not only as a proteolytic enzyme but also as a signaling molecule. In this study, we investigated the role of MT1‐MMP in the AGE/RAGE‐triggered signaling pathways in cultured rabbit smooth muscle cells (SMCs) and the molecular interaction between RAGE and MT1‐MMP in vitro and in vivo. In SMCs, AGE‐activated Rac1 and p47phox within 1 min, NADPH oxidase activity and reactive oxygen species (ROS) generation within 5 min, and NF‐κB phosphorylation within 15 min, thereby inducing redox‐sensitive molecular expression. Silencing of RAGE by small‐interfering RNA (siRNA) blocked the AGE‐induced signaling pathways. AGE‐induced geranylgeranyl transferase I (GGTase I) activity, Rac1·p47phox activation, NADPH oxidase activity, ROS generation, and molecular expression were also markedly attenuated by silencing of MT1‐MMP. An inhibitor of GGTase I mimicked the effects of MT1‐MMP‐specific siRNA. Fluorescent immunohistochemistry revealed that MT1‐MMP was partially co‐localized with RAGE in SMCs, and RAGE was found to form a complex with MT1‐MMP in both cultured SMCs and the aortae of diabetic rats by immunoprecipitation. Furthermore, MT1‐MMP and RAGE formed a complex in the aortic atherosclerotic lesions of hyperlipidemic rabbits. We show that MT1‐MMP plays a crucial role in RAGE‐activated NADPH oxidase‐dependent signaling pathways and forms a complex with RAGE in the vasculature, thus suggesting that MT1‐MMP may be a novel therapeutic target for diabetic vascular complications. J. Cell. Physiol. 226: 1554–1563, 2011. © 2010 Wiley‐Liss, Inc.
Accuracy of bedside physical examination in distinguishing categories of shock
Authors: Vazquez Rodrigo , Gheorghe Cristina , Kaufman David , Manthous Constantine A. 
Published: October 2010

AbstractHYPOTHESIS:Selected elements of a simple physical examination algorithm accurately predict categories of shock.SETTING:A 350‐bed community teaching hospital.METHODS:Resident trainees who manage all critically ill and medically unstable patients were instructed to document capillary refill, (palpated) pulse volume, skin temperature, jugular venous pressure (JVP) and lung examination in all patients with prolonged (>30 minutes hypotension <90 mmHg). Treatment was determined by house officers guided by attending physicians of record. All cases were retrospectively reviewed by a senior clinician who applied consensus criteria/definitions to categorize shock as septic, cardiogenic or hypovolemic. Operating characteristics of examination findings for predicting categories of shock were computed.RESULTS:A total of 68 patients, averaging 71 ± 16 years, were studied. A total of 37 patients were diagnosed with septic shock, 18 with cardiogenic shock of and 13 with hypovolemic shock. Capillary refill and skin temperature predicted septic shock with sensitivity of 89%, specificity of 68%, positive predictive value (PPV) of 77%, negative predictive value (NPV) of 84%, and overall accuracy of 79%. Presence of JVP >7 cmH2O was more accurate than bilateral pulmonary crackles (>1/3 from bases) in predicting cardiogenic shock for low‐output patients with sensitivity of 82%, specificity of 79%, PPV of 75%, NPV of 85%, and overall accuracy of 80%. Using just skin temperature and JVP, the bedside approach correctly diagnosed 52/68 cases (overall accuracy = 76%).CONCLUSIONS:Simple bedside clinical examination findings correctly predict categories of shock in a majority of cases. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.
Unplanned transfers to the intensive care unit: The role of the shock index
Authors: Keller A. Scott , Kirkland Lisa L. , Rajasekaran Smita Y. , Cha Stephen , Rady Mohamed Y. , Huddleston Jeanne M. 
Published: October 2010

AbstractBACKGROUND:Unplanned (unexpected) transfers to the intensive care unit (ICU) are typically preceded by physiologic instability. However, trends toward instability may be subtle and not accurately reflected by changes in vital signs. The shock index (SI) (heart rate/systolic blood pressure as an indicator of left ventricular function, reference value of 0.54) may be a simple alternative means to predict clinical deterioration.OBJECTIVE:To assess the association of the SI with unplanned ICU transfers.DESIGN:Retrospective case‐control study.SETTING:Academic medical center.PATIENTS:Fifty consecutive general medical patients with unplanned ICU transfers between 2003 and 2004 and 50 matched controls admitted to the same general medical unit between 2002 and 2004.MEASUREMENTS:Demographic data and vital signs abstracted from chart review.RESULTS:The SI was associated with unplanned ICU transfer at values of 0.85 or greater (P < 0.02; odds ratio, 3.0) and there was a significant difference between the median of worst shock indices of cases and controls (0.87 vs. 0.72; P< 0.005). There was no significant difference in age, race, admission ward, or Charlson Comorbidity Index, but hospital stay for cases was significantly longer (mean [standard deviation, SD], 14.8 [9.7] days vs. 5.7 [6.3] days; P < 0.001).CONCLUSIONS:SI is associated with unplanned transfers to the ICU from general medical units at values of 0.85 or greater. Future studies will determine whether SI is more accurate than simple vital signs as an indicator of clinical decline. If so, it may be a useful trigger to activate medical emergency or rapid response teams (RRTs). Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.
Redefining readmission risk factors for general medicine patients
Authors: Allaudeen Nazima , Vidyarthi Arpana , Maselli Judith , Auerbach Andrew 
Published: October 2010

AbstractBACKGROUND:Readmissions are costly both financially for our healthcare system and emotionally for our patients. Identifying factors that increase risk for readmissions may be helpful to focus resources to optimize the discharge process and reduce avoidable readmissions.OBJECTIVE:To identify factors associated with readmission within 30 days for general medicine patients.METHODS:We performed a retrospective observational study of an administrative database at an urban 550‐bed tertiary care academic medical center. Cohort patients were discharged from the general medicine service over a 2‐year period from June 1, 2006, to May 31, 2008. Clinical, operational, and sociodemographic factors were evaluated for association with readmission.RESULTS:Our cohort included 10,359 consecutive admissions (6805 patients) discharged from the general medicine service. The 30‐day readmission rate was 17.0%. In multivariate analysis, factors associated with readmission included black race (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.24–1.65), inpatient use of narcotics (1.33; 1.16–1.53) and corticosteroids (1.24; 1.09–1.42), and the disease states of cancer (with metastasis 1.61; 1.33–1.95; without metastasis 1.95; 1.54–2.47), renal failure (1.19; 1.05–1.36), congestive heart failure (1.30; 1.09–1.56), and weight loss (1.26; 1.09–1.47). Medicaid payer status (1.15; 0.97–1.36) had a trend toward readmission.CONCLUSION:Readmission of general medicine patients within 30 days is common and associated with several easily identifiable clinical and nonclinical factors. Identification of these risk factors can allow providers to target interventions to reduce potentially avoidable readmissions. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine
Modification of Polydivinylbenzene Microspheres by a Hydrobromination/Click‐Chemistry Protocol and their Protein‐Adsorption Properties
Authors: Durmaz Yasemin Yuksel , Karagoz Bunyamin , Bicak Niyazi , Demirkol Dilek Odaci , Yalcinkaya Esra Evrim , Timur Suna , Yagci Yusuf 
Published: October 2010

AbstractHydrophobic‐ and/or hydrophilic‐polymer‐grafted PDVB microspheres are synthesized by the combination of hydrobromination and click‐chemistry processes. The modified‐PDVB microspheres and the intermediates at various stages of synthesis are characterized using GPC, 1H NMR and FTIR spectroscopy and TGA analysis. Use of the microspheres as a support matrix for reversible protein immobilization via adsorption is investigated. The system parameters such as the adsorption conditions (i.e., enzyme concentration, medium pH) and desorption are studied and evaluated with regards to the biocatalytic activity and adsorption capacity.
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