bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversal of inflammation‐associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin
Authors: Wang Hao‐Wei , Lin Chin‐Ping , Chiu Jen‐Hwey , Chow Kuan‐Chih , Kuo Kuang‐Tai , Lin Chen‐Sung , Wang Liang‐Shun 
Published: February 2007

AbstractDihydrodiol dehydrogenase (DDH) is a member of the aldo‐keto reductases superfamily (AKR1C1–AKR1C4), which plays central roles in the metabolism of steroid hormone, prostaglandin and xenobiotics. We have previously detected overexpression of DDH as an indicator of poor prognosis and chemoresistance in human non‐small lung cancer (NSCLC). We also found DDH expression to be closely related to chronic inflammatory conditions. The aim of this study was to investigate the links between inflammation, DDH expression and drug resistance in NSCLC cells. We showed that pro‐inflammatory mediators including interleukin‐6 (IL‐6) could induce AKR1C1/1C2 expression in NSCLC cells and increase cellular resistance to cisplatin and adriamycin. This effect was nullified by Safingol, a protein kinase C inhibitor. Moreover, the expression of AKR1C1/1C2 was inversely correlated to NBS1 and apoptosis‐inducing factor (AIF). We also showed that IL‐6‐induced AKR1C1/1C2 expression and drug resistance were inhibited by wogonin and chrysin, which are major flavonoids in Scutellaria baicalensis, a widely used traditional Chinese and Japanese medicine. In conclusion, this study demonstrated novel links of pro‐inflammatory signals, AKR1C1/1C2 expression and drug resistance in NSCLC. The protein kinase C pathway may play an important role in this process. Overexpression of AKR1C1/1C2 may serve as a marker of chemoresistance. Further studies are warranted to evaluate wogonin and chrysin as a potential adjuvant therapy for drug‐resistant NSCLC, especially for those with AKR1C1/1C2 overexpression. © 2007 Wiley‐Liss, Inc.
CEBPβ, JunD and c‐Jun contribute to the transcriptional activation of the metastasis‐associated C4.4A gene
Authors: Fries Frank , Nazarenko Irina , Hess Jochen , Claas Andreas , Angel Peter , Zöller Margot 
Published: February 2007

AbstractThe glycosylphosphatidylinositol‐anchored molecule C4.4A, which shares structural features with uPAR, is frequently expressed on carcinomas with upregulated expression during tumor progression. Moreover, rare expression on nontransformed epithelial cells is strongly increased during tissue remodeling, e.g., during wound healing. This strictly regulated expression prompted us to define transcriptional activation of the C4.4A gene. C4.4A transcription was analyzed in 2 syngenic rat tumor cell lines with low or high metastatic potential, respectively. Though genomic C4.4A DNA was present in both lines, C4.4A mRNA and transcription of a reporter construct containing the C4.4A promoter was only observed in the metastasizing subline. Deletions and point mutations in the C4.4A promoter‐driven reporter construct revealed that activation of the TATA‐less, GC‐rich core promoter (−1 to −50 bp) does not suffice to initiate transcription that requires coactivation of a proximal response element (−71 to −88 bp) and can be further increased by more distal response elements (−89 to −133 bp). Mobility‐shift and cotransfection studies showed that Sp3 binding enhances C4.4A transcription, whereas potential Sp1 binding sites were ineffective. C4.4A transcription essentially requires C/EBPβ binding to a TRE/CCAAT composite element (−71 to −88 bp) as measured by ChIP assay. C4.4A transcription is strikingly enhanced by cotransfection with JunD or c‐Jun, such that C4.4A is most strongly transcribed even in the C4.4A‐negative tumor cell line after cotransfection with C/EBPβ plus JunD or c‐Jun. Thus, upregulation of C/EBPβ during tumor progression and wound repair may well provide a sufficient trigger for transcription of the C4.4A gene. © 2007 Wiley‐Liss, Inc.
Regulatory T‐cell function of adult T‐cell leukemia/lymphoma cells
Authors: Yano Hiroki , Ishida Takashi , Inagaki Atsushi , Ishii Toshihiko , Kusumoto Shigeru , Komatsu Hirokazu , Iida Shinsuke , Utsunomiya Atae , Ueda Ryuzo 
Published: February 2007

AbstractAdult T‐cell leukemia/lymphoma (ATLL) patients are highly immunocompromised, but the underlying mechanism responsible for this state remains obscure. Recent studies demonstrated that FOXP3, which is a master control gene of naturally occurring regulatory T (Treg) cells, is expressed in the tumor cells from a subset of patients with ATLL. Since most ATLL cells express both CD4 and CD25, these tumors might originate from CD4+CD25+FOXP3+ Treg cells, based on their phenotypic characteristics. However, whether ATLL cells actually function as Treg cells has not yet been clearly demonstrated. Here, we show that ATLL cells from a subset of patients are not only hypo‐responsive to T‐cell receptor‐mediated activation, but also suppress the proliferation of autologous CD4+ non‐ATLL cells. Furthermore, ATLL cells from this subset of patients secrete only small amounts of IFN‐γ, and suppress IFN‐γ production by autologous CD4+ non‐ATLL cells. These are the first data showing that ATLL cells from a subset of patients function as Treg cells in an autologous setting. The present study provides novel insights into understanding the immunopathogenesis of ATLL, i.e., how HTLV‐1‐infected cells can survive in the face of host immune responses. It also adds to our understanding of ATLL patients' severely immunocompromised state. © 2007 Wiley‐Liss, Inc.
Breast tumours following combined hormone replacement therapy express favourable prognostic factors
Authors: Borgquist Signe , Anagnostaki Lola , Jirström Karin , Landberg Göran , Manjer Jonas 
Published: February 2007

AbstractThe aim of the present study was to evaluate the association between different types of hormone replacement therapy (HRT) and risk of specific breast cancer subgroups. A population‐based prospective cohort study including 12,583 peri‐ or postmenopausal women were followed using record‐linkage with national cancer registries. During an average follow‐up of 4.5 years, 332 cases of invasive breast cancer were diagnosed. Tumour samples were available from 283 cases. These tumours were re‐evaluated according to histological type, grade, and mitotic index. Evaluation of tumours included estrogen and progesterone receptor status (ERα, ERβ and PgR), as well as expression of Ki67, HER2, cyclin D1 and p27. The incidence of breast cancer in current users of combined HRT (CHRT) was significantly higher than in non‐users. The difference corresponded to an adjusted relative risk (95% confidence interval) of 3.01 (2.35–3.84) as obtained using a Cox's proportional hazards analysis. CHRT was associated with lobular tumours (3.48:1.99–6.10), grade 1 tumours (4.46:2.79–7.13) and tumours with a low mitotic index (4.35:2.99–6.34). CHRT was not related to any specific subgroup in terms of ERα‐, ERβ‐ or PgR‐expression. CHRT was associated with low proliferating tumours, defined by the Ki67 index (3.58:2.60–4.93), HER2 amplified tumours (4.40:1.93–10.06), low expression of the oncogene cyclin D1 (3.14:2.32–4.23) and high expression of the tumour suppressor gene p27 (3.47:2.40–5.01). Use of estrogen‐alone HRT (ERT) was not associated with any statistically significant risk of breast cancer. We conclude that the use of CHRT is associated with an increased incidence of breast tumours with comparatively favourable prognostic factors. © 2007 Wiley‐Liss, Inc.
Antibody response against NY‐ESO‐1 in CHP‐NY‐ESO‐1 vaccinated patients
Authors: Kawabata Ryohei , Wada Hisashi , Isobe Midori , Saika Takashi , Sato Shuichiro , Uenaka Akiko , Miyata Hiroshi , Yasuda Takushi , Doki Yuichiro , Noguchi Yuji , Kumon Hiromi , Tsuji Kazuhide , Iwatsuki Keiji , Shiku Hiroshi , Ritter Gerd , Murphy Roger , Hoffman Eric , Old Lloyd J. , Monden Morito , Nakayama Eiichi 
Published: February 2007

AbstractNY‐ESO‐1 specific humoral responses are frequently observed in patients with various types of NY‐ESO‐1 antigen expressing tumors. In a large proportion of NY‐ESO‐1 antibody‐positive patients of NY‐ESO‐1‐specific CD8 T‐cells can also be detected suggesting that monitoring of the NY‐ESO‐1 specific humoral immune response may be a relevant and more practical surrogate for estimating the overall immune response against NY‐ESO‐1 in clinical vaccine studies. We have immunized 9 cancer patients with full length NY‐ESO‐1 protein formulated with cholesterol‐bearing hydrophobized pullulan (CHP‐NY‐ESO‐1) and investigated the humoral immune responses against NY‐ESO‐1. Seven patients were NY‐ESO‐1 antibody‐negative and 2 patients were positive prior to vaccination. Vaccination with CHP‐NY‐ESO‐1 resulted in the induction or increase of NY‐ESO‐1 antibody responses in all 9 patients immunized. Epitope analysis revealed 5 regions in the NY‐ESO‐1 protein molecule that were recognized by antibodies induced after vaccination. The 5 regions were also recognized by antibodies present in nonvaccinated, NY‐ESO‐1 antibody‐positive cancer patients. A peptide spanning amino acids 91–108 was recognized in 6 out of 9 vaccinated patients and in 8 out of 9 nonvaccinated, sero‐positive patients, being the most dominant antigenic epitope in NY‐ESO‐1 for antibody recognition in cancer patients. In conclusion, we showed that CHP‐NY‐ESO‐1 protein vaccination had a potent activity for inducing humoral immune responses against NY‐ESO‐1 antigen in cancer patients. The antigenic epitopes recognized by antibodies in the vaccinated patients were similar to those recognized in cancer patients with spontaneous humoral immunity against NY‐ESO‐1. © 2007 Wiley‐Liss, Inc.
Biaxial mechanical evaluation of cholecyst‐derived extracellular matrix: A weakly anisotropic potential tissue engineered biomaterial
Authors: Coburn James C. , Brody Sarah , Billiar Kristen L. , Pandit Abhay 
Published: February 2007

AbstractA new acellular, natural, biodegradable matrix has been discovered in the cholecyst‐derived extracellular matrix (CEM). This matrix is rich in collagen and contains several other macromolecules useful in tissue remodeling. In this study, the principal material axes, collagen fiber orientations, and biaxial mechanical properties in a physiological loading regime were characterized. Fiber direction was determined by polarized light microscopy, and the principal axes and degree of anisotropy were determined mechanically. Macroscopic equibiaxial strain tests were then conducted on preconditioned specimens. While 13% of the area of CEM contains collagen fibers oriented between 50° and 60° from the neck‐fundus axis, the principal material axis was oriented 63° ± 13.7°, with an aspect ratio of 0.11 ± 0.06, indicating a weak anisotropy in that direction. Under biaxial loading, CEM exhibited a large toe region followed by an exponential rise in stress in both principal and perpendicular axis directions, similar to other materials currently under research. There was no significant difference between the biaxial stress–strain profile and the burst stress–strain profile. The results demonstrate that CEM is weakly anisotropic and it has the ability to support large strains across a physiological loading regime. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Discrete crosslinked fibrin microthread scaffolds for tissue regeneration
Authors: Cornwell Kevin G. , Pins George D. 
Published: February 2007

AbstractIn this study, we report on the development of discrete fibrin microthreads as well as novel scaffolds composed of arrays of fibrin threads. These scaffolds exhibit mechanical properties that are significantly greater than fibrin gels and cellular responses suggesting that the materials are conducive to the development of organized, aligned tissues. Fibrin microthreads were produced by coextruding solutions of 70 mg/mL fibrinogen and 6 U/mL thrombin through small diameter polyethylene tubing. Uncrosslinked fibrin microthreads averaged 55–65 μm in hydrated diameter and achieved ultimate tensile strengths approaching 4.5 MPa. The strengths and stiffnesses of the microthreads were approximately twofold greater when the materials were treated with exposure to ultraviolet (UV) light. Although UV crosslinking attenuated fibroblast proliferation, uncrosslinked fibrin microthreads supported fibroblast attachment, proliferation, and alignment, suggesting that they represent a viable biomaterial for the aligned regeneration of tissues. Because of the physiologic roles of fibrin matrices in the early phase of wound healing, we anticipate that these fibrin‐based microthreads will direct the spatially and temporally complex processes of cell‐mediated tissue ingrowth and regeneration. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Influence of TiO2 and Ag2O addition on tricalcium phosphate ceramics
Authors: Seeley Zachary , Bandyopadhyay Amit , Bose Susmita 
Published: February 2007

AbstractDegradation of implanted ceramics allows for bone in‐growth and eventual replacement with natural tissue. Calcium phosphate‐based materials have gained the most significant attention because of their excellent biocompatibility and compositional similarities to natural bone. Adding various dopants to these ceramics significantly influences critical properties. In this study, tricalcium phosphate (TCP) compacts were fabricated via uniaxial compression with four compositions: (i) pure TCP, (ii) TCP with 1.0 wt % TiO2, (iii) TCP with 0.5 wt % Ag2O, and (iv) ternary of TCP and 1.0 wt % TiO2, and 0.5 wt % Ag2O. These compacts were sintered at 1250°C for 4 h to obtain dense ceramic structures. Phase analyses were carried out using an X‐ray diffractometer. The presence of TiO2 in TCP improved densification and increased compression strength from 70 (±25) to 145 (±40) MPa. The ternary composition had the highest density and compression strength of 180 (±15) MPa. Human osteoblast cell growth behavior was studied using an osteoprecursor cell line (OPC 1) to assure that the biocompatibility of these ceramics was not altered due to the dopants. For long‐term biodegradation studies, density, weight change, surface microstructure, and uniaxial compression strength were measured as a function of time in a simulated body fluid (SBF). Weight gain in SBF correlated strongly with precipitation viewed in the inter‐connected pores of the samples. After 3 months in SBF, a 35% drop in compression strength was noticed for pure TCP, but for doped compositions, no strength loss was noticed. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Micromechanical bending of single collagen fibrils using atomic force microscopy
Authors: Yang Lanti , van der Werf Kees O. , Koopman Bart F.J.M. , Subramaniam Vinod , Bennink Martin L. , Dijkstra Pieter J. , Feijen Jan 
Published: February 2007

AbstractA new micromechanical technique was developed to study the mechanical properties of single collagen fibrils. Single collagen fibrils, the basic components of the collagen fiber, have a characteristic highly organized structure. Fibrils were isolated from collagenous materials and their mechanical properties were studied with atomic force microscopy (AFM). In this study, we determined the Young's modulus of single collagen fibrils at ambient conditions from bending tests after depositing the fibrils on a poly(dimethyl siloxane) (PDMS) substrate containing micro‐channels. Force‐indentation relationships of freely suspended collagen fibrils were determined by loading them with a tip‐less cantilever. From the deflection‐piezo displacement curve, force‐indentation curves could be deduced. With the assumption that the behavior of collagen fibrils can be described by the linear elastic theory of isotropic materials and that the fibrils are freely supported at the rims, a Young's modulus of 5.4 ± 1.2 GPa was determined. After cross‐linking with glutaraldehyde, the Young's modulus of a single fibril increases to 14.7 ± 2.7 GPa. When it is assumed that the fibril would be fixed at the ends of the channel the Young's moduli of native and cross‐linked collagen fibrils are calculated to be 1.4 ± 0.3 GPa and 3.8 ± 0.8 GPa, respectively. The minimum and maximum values determined for native and glutaraldehyde cross‐linked collagen fibrils represent the boundaries of the Young's modulus. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Value of sonography for follow‐up of mediastinal lymphadenopathy in children with tuberculosis
Authors: Bosch‐Marcet Joaquim , Serres‐Créixams Xavier , Borrás‐Pérez Victoria , Coll‐Sibina Maria Teresa , Guitet‐Juliá Montserrat , Coll‐Rosell Elena 
Published: February 2007

AbstractPurpose.To assess the clinical value of sonography for the follow‐up of mediastinal lymphadenopathy in children diagnosed with pulmonary tuberculosis (TB).Methods.We conducted a retrospective review of the medical records of 21 children (9 boys, 12 girls) with a mean age of 6 years (range, 7.4 months to 18 years) who had a positive intradermal tuberculin skin test. All patients underwent thorough history‐taking, physical examination, frontal and lateral chest radiographs, and sonographic study of the mediastinum. The mediastinum was accessed through the suprasternal and left parasternal approaches. The presence of 1 or more masses with an ovoid or round shape and hypoechoic appearance in the anterior or middle mediastinum was recorded. A comparison was made between the results of the sonographic examination of the mediastinum before administration of anti‐TB agents and after 3 months of treatment.Results.Pulmonary radiographic findings were suggestive of TB in 17 patients and were uncertain in 4 patients. Sonographic examination, however, detected mediastinal lymphadenopathy in all patients. A comparison of pretreatment mediastinal sonograms with those obtained after 3 months of anti‐TB treatment showed a marked reduction of lymph node involvement in 17 patients (80.9%). In the remaining 4 patients, mediastinal lymphadenopathy was still present.Conclusion.Mediastinal sonography appears to be a valuable tool for the diagnosis of TB and in the monitoring of response to treatment in children. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007
Which observations from the complete blood cell count predict mortality for hospitalized patients?
Authors: Kho Abel N , Hui Siu , Kesterson Joe G. , McDonald Clement J. 
Published: February 2007

AbstractBACKGROUND:Information on the prognostic utility of the admission complete blood count (CBC) and differential count is lacking.OBJECTIVE:To identify independent predictors of mortality from the varied number and morphology of cells in the complete blood count defined as a hemogram, automated five cell differential count and manual differential count.DESIGN:Retrospective cohort study and chart review.SETTING:Wishard Memorial Hospital, a large urban primary care hospital.PATIENTS:A total of 46,522 adult inpatients admitted over 10 years to Wishard Memorial Hospital—from January 1993 through December 2002.wINTERVENTION:None.MEASUREMENTS:Thirty‐day mortality measured from day of admission as determined by electronic medical records and Indiana State death records.RESULTS:Controlling for age and sex, the multivariable regression model identified 3 strong independent predictors of 30‐day mortality—nucleated red blood cells (NRBCs), burr cells, and absolute lymphocytosis—each of which was associated with a 3‐fold increase in the risk of death within 30 days. The presence of nucleated RBCs was associated with a 30‐day mortality rate of 25.5% across a range of diagnoses, excluding patients with sickle‐cell disease and obstetric patients, for whom NRBCs were not associated with increased mortality. Having burr cells was associated with a mortality rate of 27.3% and was found most commonly in patients with renal or liver failure. Absolute lymphocytosis predicted poor outcome in patients with trauma and CNS injury.CONCLUSIONS:Among patients admitted to Wishard Memorial Hospital, the presence of nucleated RBCs, burr cells, or absolute lymphocytosis at admission was each independently associated with a 3‐fold increase in risk of death within 30 days of admission. Journal of Hospital Medicine 2007;2:5–12. © 2007 Society of Hospital Medicine.
Third‐year medical students' evaluation of hospitalist and nonhospitalist faculty during the inpatient portion of their pediatrics clerkships
Authors: Geskey Joseph M. , Kees‐Folts Deborah 
Published: February 2007

AbstractBACKGROUND:Although the data on the impact of hospitalist programs on the inpatient education of medical students during their internal medicine clerkships are favorable, the data is limited on the inpatient educational experience of medical students during their pediatric clerkships. The purpose of this study was to compare the evaluations of hospitalist and nonhospitalist faculty of third‐year medical students during their inpatient pediatrics rotations.METHODS:We performed a retrospective study of the evaluations of third‐year medical student of hospitalist and nonhospitalist faculty during their inpatient pediatrics rotations at Penn State Children's Hospital from July 1999 through September 2000. Using a 4‐point scale, students gave an overall evaluation and also rated the hospitalist and nonhospitalist faculty on effectiveness as teachers, effectiveness as pediatricians, and effectiveness as student advocates. Using the same 4‐point scale, students rated the following aspects of the rotation: ward rounds, sick newborn care, well newborn care, outpatient clinics, private physician's office, noon conferences, and morning report.RESULTS:A total of 67 students rotated on the pediatric inpatient service during the study period; 35 students rotated with 2 hospitalists, and 32 students rotated with 8 nonhospitalists. All 67 students (100%) submitted an evaluation. The hospitalists received higher scores than nonhospitalists on effectiveness as teachers (3.87 vs. 2.91; P < 0.001), effectiveness as pediatricians (3.94 vs. 3.25; P < .001), effectiveness as student advocates (3.76 vs. 2.97; P < .001), and in the overall evaluation (3.93 vs. 3.06; P < .001). Ward rounds were rated as more beneficial when conducted by hospitalists then when conducted by nonhospitalists (3.15 vs. 2.58; P < .006).CONCLUSIONS:Hospitalists were perceived by third‐year medical students as providing more effective teaching and more satisfying overall rotations than were nonhospitalists during the inpatient portion of the students' pediatric clerkships. Further studies that examine inpatient systems, particularly as they relate to the acquisition of knowledge and the development of effective communication skills in medical learners, are needed. Journal of Hospital Medicine 2007;2:17–22. © 2007 Society of Hospital Medicine.