bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of electrolyte constituents on corrosion behaviour of PEO coatings on magnesium alloys
Authors: Ghasemi A. , Scharnagl N. , Blawert C. , Dietzel W. , Kainer K. U.
Published: September 2008

AM50 magnesium alloy is treated by PEO process using four different electrolytes which are combination of K3PO4 and Na3PO4 plus two different hydroxides, i.e. KOH and NaOH. Basic properties of the electrolyte such as pH, conductivity and breakdown voltage were measured. Moreover, coatings were characterised by scanning electron microscopy for the surface morphology and cross sectional study, X-ray diffraction for determination of phase composition and electrochemical impedance spectroscopy (EIS) for evaluation of corrosion resistance. The results indicate that KOH solutions need higher breakdown voltage and result in higher thickness of coatings. The values of the latter parameters are in the range of 150–160 V and 14–17 μm respectively. While those of NaOH solutions are in the range of 106–116 V and 5–6 μm thick. The final results show that presence of KOH in the solutions leads to a better corrosion performance of the coating compared to NaOH.
Characterisation of detonation gun sprayed Cr3C2–25NiCr coatings on Ni and Fe based superalloys
Authors: Kamal S. , Jayaganthan R. , Prakash S.
Published: September 2008

Cr3C2–25NiCr coatings are essential to provide protection against both wear and corrosion of superalloys particularly in the temperature range up to 900–1000°C. The Cr3C2–25NiCr coatings were deposited on the Fe and Ni based superalloys by D gun spray technique and subsequently investigated for their microstructural characteristics such as coating thickness, porosity, phase formation, microhardness, surface and cross-sectional morphologies. The coatings showed a dense microstructure with porosity contents less than 0·69%. The carbide grains of different size are uniformly cladded with the metallic binder and located around the splat boundaries as observed in the coatings. Lower carbide dissolution and its uniform distribution ensured a better binder protection in the coatings. High cohesive strength of the individual splats and high volume fraction of carbides contributed for the higher microhardness values of the coatings (775–1200 HV).
Failure mechanism of organic coatings overlaid on arc sprayed coatings
Authors: Fu D. X. , Xu B. S. , Zhang W. , Wei S. C. , Liu Y.
Published: September 2008

A general mechanism of corrosion degradation of organic coatings overlaid on Al and Zn–Al–Mg–RE (rare earth) coatings was investigated. The metallic coatings were prepared by the high velocity arc spraying (HVAS) technology. Artificial defects were introduced in the organic coatings and the samples were immersed in 5 wt-%NaCl aqueous solution. After 430 h, the different microstructures of corrosion products in the defects were studied by scanning electron microscopy. The microstructure of corrosion products of the HVAS Zn–Al–Mg–RE coating was more compact than that of the HVAS Al coating. The compact corrosion products were better barriers against chloride ions and water permeation, and the defects in the system were blocked by the corrosion products.
Study of growth mechanism of zinc hot dip galvanising coatings
Authors: Pistofidis N. , Chaliampalias D. , Vourlias G.
Published: September 2008

Zinc hot dip galvanising is one of the most effective methods for the corrosion protection of ferrous materials. However, although its efficiency is undisputable, the exact growth mechanism of these coatings is still under question. In the present work, the diffusivity of liquid zinc in carbon steels was measured with electron microscopy. Furthermore, the change of the free Gibbs energy was calculated for each phase of the coating. Nevertheless, the coating structure was microscopically studied for an extremely short immersion time (about 1 s). In this way, it was deduced that the coating growth begins with the nucleation of the ζ phase of the Fe–Zn system. The γ and λ phases grow with zinc diffusion through the ζ phase. The η phase is mechanically drifted due to the surface tension of the liquid metal.
Geldanamycin-induced Lyn dissociation from aberrant Hsp90-stabilized cytosolic complex is an early event in apoptotic mechanisms in B-chronic lymphocytic leukemia
Authors: Trentin Livio , Frasson Martina , Donella-Deana Arianna , Frezzato Federica , Pagano Mario A. , Tibaldi Elena , Gattazzo Cristina , Zambello Renato , Semenzato Gianpietro , Brunati Anna M.
Published: September 2008

Lyn, a tyrosine kinase belonging to the Src family, plays a key role as a switch molecule that couples the B-cell receptor to downstream signaling. In B-CLL cells, Lyn is overexpressed, anomalously present in the cytosol, and displays a high constitutive activity, compared with normal B lymphocytes. The aim of this work was to gain insights into the molecular mechanisms underlying these aberrant properties of Lyn, which have already been demonstrated to be related to defective apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Herein, Lyn is described to be in an active conformation as integral component of an aberrant cytosolic 600-kDa multiprotein complex in B-CLL cells, associated with several proteins, such as Hsp90 through its catalytic domain, and HS1 and SHP-1L through its SH3 domain. In particular, Hsp90 appears tightly bound to cytosolic Lyn (CL), thus stabilizing the aberrant complex and converting individual transient interactions into stable ones. We also demonstrate that treatment of B-CLL cells with geldanamycin, an Hsp90 inhibitor already reported to induce cell death, is capable of dissociating the CL complex in the early phases of apoptosis and thus inactivating CL itself. These data identify the CL complex as a potential target for therapy in B-CLL.
Expanded cells in monoclonal TCR-αβ+/CD4+/NKa+/CD8−/+dim T-LGL lymphocytosis recognize hCMV antigens
Authors: Rodríguez-Caballero Arancha , García-Montero Andrés C. , Bárcena Paloma , Almeida Julia , Ruiz-Cabello Francisco , Tabernero Maria Dolores , Garrido Pilar , Muñoz-Criado Santiago , Sandberg Yorick , Langerak Anton W. , González Marcos , Balanzategui Ana , Orfao Alberto
Published: September 2008

Recent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal T-cell receptor (TCR)–αβ+/CD4+/NKa+/CD8−/+dim T-large granular lymphocyte (LGL) lymphocytosis. Because healthy persons show (oligo)clonal expansions of human cytomegalovirus (hCMV)–specific TCRVβ+/CD4+/cytotoxic/memory T cells, we investigate the potential involvement of hCMV in the origin and/or expansion of monoclonal CD4+ T-LGL. Peripheral blood samples from patients with monoclonal TCR-αβ+/CD4+ T-LGL lymphocytosis and other T-chronic lymphoproliferative disorders were evaluated for the specific functional response against hCMV and hEBV whole lysates as well as the “MQLIPDDYSNTHSTRYVTVK” hCMV peptide, which is specifically loaded in HLA-DRB1*0701 molecules. A detailed characterization of those genes that underwent changes in T-LGL cells responding to hCMV was performed by microarray gene expression profile analysis. Patients with TCR-αβ+/CD4+ T-LGL displayed a strong and characteristic hCMV-specific functional response, reproduced by the hCMV peptide in a subset of HLA-DRB1*0701+ patients bearing TCRVβ13.1+ clonal T cells. Gene expression profile showed that the hCMV-induced response affects genes involved in inflammatory and immune responses, cell cycle progression, resistance to apoptosis, and genetic instability. This is the first study providing evidence for the involvement of hCMV in the ontogeny of CD4+ T-LGL, emerging as a model disorder to determine the potential implications of quite a focused CD4+/cytotoxic immune response.
IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils
Authors: Didichenko Svetlana A. , Spiegl Nicole , Brunner Thomas , Dahinden Clemens A.
Published: September 2008

The contribution of basophils in allergic disease and other Th2-type immune responses depends on their persistence at sites of inflammation, but the ligands and molecular pathways supporting basophil survival are largely unknown. The comparison of rates of apoptosis and of the expression of antiapoptotic proteins in different human granulocyte types revealed that basophils have a considerably longer spontaneous life span than neutrophils and eosinophils consistent with high levels of constitutive Bcl-2 expression. Interleukin-3 (IL-3) is the only ligand that efficiently protects basophils from apoptosis as evidenced by screening a large number of stimuli. IL-3 up-regulates the expression of the antiapoptotic proteins cIAP2, Mcl-1, and Bcl-XL and induces a rapid and sustained de novo expression of the serine/threonine kinase Pim1 that closely correlates with cytokine-enhanced survival. Inhibitor studies and protein transduction of primary basophils using wild-type and kinase-dead Pim1-Tat fusion-proteins demonstrate the functional importance of Pim1 induction in the IL-3–enhanced survival. Our data further indicate that the antiapoptotic Pim1-mediated pathway operates independently of PI3-kinase but involves the activation of p38 MAPK. The induction of Pim1 leading to PI3-kinase–independent survival as described here for basophils may also be a relevant antiapoptotic mechanism in other terminally differentiated leukocyte types.
Pak1 regulates multiple c-Kit mediated Ras-MAPK gain-in-function phenotypes in Nf1+/− mast cells
Authors: McDaniel Andrew S. , Allen Jayme D. , Park Su-Jung , Jaffer Zahara M , Michels Elizabeth G. , Burgin Sarah J. , Chen Shi , Bessler Waylan K. , Hofmann Clemens , Ingram David A. , Chernoff Jonathan , Clapp D. Wade
Published: September 2008

Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by mutations in the NF1 locus, which encodes neurofibromin, a negative regulator of Ras. Patients with NF1 develop numerous neurofibromas, which contain many inflammatory mast cells that contribute to tumor formation. Subsequent to c-Kit stimulation, signaling from Ras to Rac1/2 to the MAPK pathway appears to be responsible for multiple hyperactive mast cell phenotypes; however, the specific effectors that mediate these functions remain uncertain. p21-activated kinase 1 (Pak1) is a downstream mediator of Rac1/2 that has been implicated as a positive regulator of MAPK pathway members and is a modulator of cell growth and cytoskeletal dynamics. Using an intercross of Pak 1−/− mice with Nf1+/− mice, we determined that Pak1 regulates hyperactive Ras-dependent proliferation via a Pak1/Erk pathway, whereas a Pak1/p38 pathway is required for the increased migration in Nf1+/− mast cells. Furthermore, we confirmed that loss of Pak1 corrects the dermal accumulation of Nf1+/− mast cells in vivo to levels found in wild-type mice. Thus, Pak1 is a novel mast cell mediator that functions as a key node in the MAPK signaling network and potential therapeutic target in NF1 patients.
Prophylactic infusion of cytomegalovirus-specific cytotoxic T lymphocytes stimulated with Ad5f35pp65 gene-modified dendritic cells after allogeneic hemopoietic stem cell transplantation
Authors: Micklethwaite Kenneth P. , Clancy Leighton , Sandher Upinder , Hansen Anna M. , Blyth Emily , Antonenas Vicki , Sartor Mary M. , Bradstock Kenneth F. , Gottlieb David J.
Published: September 2008

Cytomegalovirus (CMV) and its therapy continue to contribute to morbidity and mortality in hemopoietic stem cell transplantation (HSCT). Many studies have demonstrated the feasibility of in vitro generation of CMV-specific T cells for adoptive immunotherapy of CMV. Few clinical trials have been performed showing the safety and efficacy of this approach in vivo. In this study, donor-derived, CMV-specific T cells were generated for 12 adult HSCT patients by stimulation with dendritic cells transduced with an adenoviral vector encoding the CMV-pp65 protein. Patients received a prophylactic infusion of T cells after day 28 after HSCT. There were no infusion related adverse events. CMV DNAemia was detected in 4 patients after infusion but was of low level. No patient required CMV-specific pharmacotherapy. Immune reconstitution to CMV was demonstrated by enzyme linked immunospot assay in all recipients with rapid increases in predominantly CMV-pp65 directed immunity in 5. Rates of graft-versus-host disease, infection, and death were not increased compared with expected. These results add to the growing evidence of the safety and efficacy of immunotherapy of CMV in HSCT, supporting its more widespread use. This study was registered at www.anzctr.org.au as #ACTRN12605000213640.
Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapy
Authors: Hughes Timothy P. , Branford Susan , White Deborah L. , Reynolds John , Koelmeyer Rachel , Seymour John F. , Taylor Kerry , Arthur Chris , Schwarer Anthony , Morton James , Cooney Julian , Leahy Michael F. , Rowlings Philip , Catalano John , Hertzberg Mark , Filshie Robin , Mills Anthony K. , Fay Keith , Durrant Simon , Januszewicz Henry , Joske David , Underhill Craig , Dunkley Scott , Lynch Kevin , Grigg Andrew
Published: September 2008

We conducted a trial in 103 patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML) using imatinib 600 mg/day, with dose escalation to 800 mg/day for suboptimal response. The estimated cumulative incidences of complete cytogenetic response (CCR) by 12 and 24 months were 88% and 90%, and major molecular responses (MMRs) were 47% and 73%. In patients who maintained a daily average of 600 mg of imatinib for the first 6 months (n = 60), MMR rates by 12 and 24 months were 55% and 77% compared with 32% and 53% in patients averaging less than 600 mg (P = .037 and .016, respectively). Dose escalation was indicated for 17 patients before 12 months for failure to achieve, or maintain, major cytogenetic response at 6 months or CCR at 9 months but was only possible in 8 patients (47%). Dose escalation was indicated for 73 patients after 12 months because their BCR-ABL level remained more than 0.01% (international scale) and was possible in 45 of 73 (62%). Superior responses achieved in patients able to tolerate imatinib at 600 mg suggests that early dose intensity may be critical to optimize response in CP-CML. The trial was registered at www.ANZCTR.org.au as #ACTRN12607000614493.
Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia
Authors: Yang Jun J. , Bhojwani Deepa , Yang Wenjian , Cai Xiangjun , Stocco Gabriele , Crews Kristine , Wang Jinhua , Morrison Debra , Devidas Meenakshi , Hunger Stephen P. , Willman Cheryl L. , Raetz Elizabeth A. , Pui Ching-hon , Evans William E. , Relling Mary V. , Carroll William L.
Published: September 2008

The underlying pathways that lead to relapse in childhood acute lymphoblastic leukemia (ALL) are unknown. To comprehensively characterize the molecular evolution of relapsed childhood B-precursor ALL, we used human 500K single-nucleotide polymorphism arrays to identify somatic copy number alterations (CNAs) in 20 diagnosis/relapse pairs relative to germ line. We identified 758 CNAs, 66.4% of which were less than 1 Mb, and deletions outnumbered amplifications by approximately 2.5:1. Although CNAs persisting from diagnosis to relapse were observed in all 20 cases, 17 patients exhibited differential CNA patterns from diagnosis to relapse. Of the 396 CNAs observed in 20 relapse samples, only 69 (17.4%) were novel (absent in the matched diagnosis samples). EBF1 and IKZF1 deletions were particularly frequent in this relapsed ALL cohort (25.0% and 35.0%, respectively), suggesting their role in disease recurrence. In addition, we noted concordance in global gene expression and DNA copy number changes (P = 2.2 × 10−16). Finally, relapse-specific focal deletion of MSH6 and, consequently, reduced gene expression were found in 2 of 20 cases. In an independent cohort of children with ALL, reduced expression of MSH6 was associated with resistance to mercaptopurine and prednisone, thereby providing a plausible mechanism by which this acquired deletion contributes to drug resistance at relapse.
Nonoperative management of blunt renal trauma: Is routine early follow-up imaging necessary?
Authors: Malcolm John B , Derweesh Ithaar H , Mehrazin Reza , DiBlasio Christopher J , Vance David D , Joshi Salil , Wake Robert W , Gold Robert
Published: September 2008

Background

There is no consensus on the role of routine follow-up imaging during nonoperative management of blunt renal trauma. We reviewed our experience with nonoperative management of blunt renal injuries in order to evaluate the utility of routine early follow-up imaging.

Methods

We reviewed all cases of blunt renal injury admitted for nonoperative management at our institution between 1/2002 and 1/2006. Data were compiled from chart review, and clinical outcomes were correlated with CT imaging results.

Results

207 patients were identified (210 renal units). American Association for the Surgery of Trauma (AAST) grades I, II, III, IV, and V were assigned to 35 (16%), 66 (31%), 81 (39%), 26 (13%), and 2 (1%) renal units, respectively. 177 (84%) renal units underwent routine follow-up imaging 24–48 hours after admission. In three cases of grade IV renal injury, a ureteral stent was placed after serial imaging demonstrated persistent extravasation. In no other cases did follow-up imaging independently alter clinical management. There were no urologic complications among cases for which follow-up imaging was not obtained.

Conclusion

Routine follow-up imaging is unnecessary for blunt renal injuries of grades I-III. Grade IV renovascular injuries can be followed clinically without routine early follow-up imaging, but urine extravasation necessitates serial imaging to guide management decisions. The volume of grade V renal injuries in this study is not sufficient to support or contest the need for routine follow-up imaging.
Understanding ageing: Biomedical and bioengineering approaches, the immunologic view
Authors: Bulati Matteo , Pellicanò Mariavaleria , Vasto Sonya , Colonna-Romano Giuseppina
Published: September 2008

During the past century, humans have gained more years of average life expectancy than in the last 10,000 years; we are now living in a rapidly ageing world. The sharp rise in life expectancy, coupled to a steady decline in birth rates in all developed countries, has led to an unprecedented demographic revolution characterized by an explosive growth in the number and proportion of older people. Ageing is a complex process that negatively impacts the development of the immune system and its ability to function. Progressive changes in the T and B cell systems over the life span have a major impact on the capacity to respond to immune challenge. These cumulative age-associated changes in immune competence are termed Immunosenescence: some immunological parameters are commonly notably reduced in the elderly and, reciprocally good function is tightly correlated to health status. Hence, a better understanding of Immunosenescence and the development of new strategies to counteract it are essential for improving the quality of life of the elderly population.
Accelerometer-based wireless body area network to estimate intensity of therapy in post-acute rehabilitation
Authors: Choquette Stéphane , Hamel Mathieu , Boissy Patrick
Published: September 2008

Background

It has been suggested that there is a dose-response relationship between the amount of therapy and functional recovery in post-acute rehabilitation care. To this day, only the total time of therapy has been investigated as a potential determinant of this dose-response relationship because of methodological and measurement challenges. The primary objective of this study was to compare time and motion measures during real life physical therapy with estimates of active time (i.e. the time during which a patient is active physically) obtained with a wireless body area network (WBAN) of 3D accelerometer modules positioned at the hip, wrist and ankle. The secondary objective was to assess the differences in estimates of active time when using a single accelerometer module positioned at the hip.

Methods

Five patients (77.4 ± 5.2 y) with 4 different admission diagnoses (stroke, lower limb fracture, amputation and immobilization syndrome) were recruited in a post-acute rehabilitation center and observed during their physical therapy sessions throughout their stay. Active time was recorded by a trained observer using a continuous time and motion analysis program running on a Tablet-PC. Two WBAN configurations were used: 1) three accelerometer modules located at the hip, wrist and ankle (M3) and 2) one accelerometer located at the hip (M1). Acceleration signals from the WBANs were synchronized with the observations. Estimates of active time were computed based on the temporal density of the acceleration signals.

Results

A total of 62 physical therapy sessions were observed. Strong associations were found between WBANs estimates of active time and time and motion measures of active time. For the combined sessions, the intraclass correlation coefficient (ICC) was 0.93 (P ≤ 0.001) for M3 and 0.79 (P ≤ 0.001) for M1. The mean percentage of differences between observation measures and estimates from the WBAN of active time was -8.7% ± 2.0% using data from M3 and -16.4% ± 10.4% using data from M1.

Conclusion

WBANs estimates of active time compare favorably with results from observation-based time and motion measures. While the investigation on the association between active time and outcomes of rehabilitation needs to be studied in a larger scale study, the use of an accelerometer-based WBAN to measure active time is a promising approach that offers a better overall precision than methods relying on work sampling. Depending on the accuracy needed, the use of a single accelerometer module positioned on the hip may still be an interesting alternative to using multiple modules.
Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions
Authors: Parente Paola , Coli Antonella , Massi Guido , Mangoni Antonella , Fabrizi Manuela M , Bigotti Giulio
Published: September 2008

Background

Reported data indicate that cancer cells have increased rates of glucose metabolism, as determined by 18FDG-PET imaging in patients with malignancies. The results of many studies have demonstrated that the expression of glucose transporters, especially Glut-1, is increased in a variety of malignancies. This study was undertaken to assess the differential expression of Glut-1 and Glut-3 by benign and malignant melanocytic lesions.

Methods

Immunohistochemical staining for Glut-1 and Glut-3 was performed on paraffin-embedded tissue sections prepared from melanocytic nevi (12 cases), Spitz nevi (12 cases) and primary cutaneous malignant melanomas (20 cases).

Results

We observed immunoreactivity for Glut-1 in all melanocytic nevi, 9 of the 12 Spitz nevi and in 9 of the 20 malignant melanomas, whereas Glut-3 was expressed in all the melanocytic lesions, both benign and malignant.

Conclusion

These findings indicate that the glucose transporters Glut-1 and Glut-3 play a role in the glucose metabolism of melanocytic cells. Glut-1 was present in the majority of benign nevi, whereas its expression was downregulated in 55% of malignant melanomas. Our results suggest that glucose transporter Glut-1 expression can significantly discriminate between human malignant melanoma and benign melanocytic nevi, and support the idea that additional mechanisms other than Glut-1 may contribute to glucose uptake in melanomas.
Vertebral artery dissection presenting with ispilateral acute C5 and C6 sensorimotor radiculopathy: A case report
Authors: Tabatabai Ghazaleh , Schöber Wolfgang , Ernemann Ulrike , Weller Michael , Krüger Rejko
Published: September 2008

Spinal manifestations of vertebral artery dissection (VAD) are rare events and are typically symptomatic with neck pain and ischemic brain injury. We report a patient presenting with unusual peripheral paresis of the right upper limb due to an intramural hematoma of the right vertebral artery with local compression of C5 and C6 as the cause of cervical radiculopathy. These symptoms completely resolved after anticoagulation and physical therapy.
Interleukin-6 acts in the fashion of a classical chemokine on monocytic cells by inducing integrin activation, cell adhesion, actin polymerization, chemotaxis, and transmigration
Authors: Clahsen Thomas , Schaper Fred
Published: September 2008

Macrophages contribute to the innate immune response by eliminating bacteria, viral particles, and apoptotic bodies. They develop from circulating monocytes. In case of an infection, monocytes attach to the endothelial cells of the blood vessels, migrate along the endothelial cells, leave the circulatory system to enter the inflammatory tissue, and differentiate into macrophages. Cell migration is induced frequently by chemokines that act through G-protein-coupled receptors. Only a few cytokines signaling through single-transmembrane domain receptors have been shown to induce cell migration. Often, this potential depends on the induction of classical chemokines and is not a direct cellular effect. Here, we discovered IL-6 as a potent stimulant for monocytic cell migration. Furthermore, we present data about IL-6-induced integrin activation, cell attachment, actin polymerization, fibronectin-dependent migration, and transmigration through a layer of endothelial cells. Our results show that IL-6 fulfills all biological properties to mediate cell migration of monocytic cells, which may contribute to the proinflammatory potential of IL-6.
Normal mouse kidneys contain activated and CD3+CD4−CD8− double-negative T lymphocytes with a distinct TCR repertoire
Authors: Ascon Dolores B , Ascon Miguel , Satpute Shailesh , Lopez-Briones Sergio , Racusen Lorraine , Colvin Robert B , Soloski Mark J , Rabb Hamid
Published: September 2008

Healthy liver, intestine, lung, and skin harbor resident lymphocytes with conventional and unconventional phenotypes. Lymphocytes also have been detected in healthy mice kidneys; however, these cells have not been well studied and have been largely overlooked. To better characterize the intra-renal lymphocytes, we extensively perfused C57BL/6J mice with PBS and then isolated mononuclear cells for flow cytometry analysis. We observed T cells, B cells, and NK cells in normal mice kidneys after extensive perfusion. Approximately 50% of kidney T lymphocytes expressed intermediate levels of CD3 (CD3int T cells). Similar to liver and lung, a high percentage of unconventional CD3+CD4−CD8− double-negative T cells was observed in normal mice kidneys, from which 11% expressed B220 antigen. Unlike the spleen and blood, the classic CD4+ and CD8+ T lymphocytes in the kidney had a high proportion of activated CD69+ and effector/memory CD44CD62L ligand phenotypes. Also, a small percentage of CD4+CD25+forkhead box p3+ and NKT cells was observed in perfused and exanguinated kidneys. In addition, a distinct TCR repertoire was found on intra-renal conventional and unconventional T cells compared with those from the spleen. Finally, after 24 h of renal ischemia reperfusion injury (IRI), increased production of cytokines IFN-γ and TNF-α by CD4+ and CD8+ T cells, isolated from perfused kidneys, was observed. These data suggest that some of these cells harbored in the kidney could be implicated in the immune response of the IRI pathogenic process.
Type 1 Receptor Tyrosine Kinase Profiles Identify Patients With Enhanced Benefit From Anthracyclines in the BR9601 Adjuvant Breast Cancer Chemotherapy Trial
Authors: Bartlett John M.S. , Munro Alison , Cameron David A. , Thomas Jeremy , Prescott Robin , Twelves Chris J.
Published: September 2008

Purpose

Patients with early breast cancer who receive anthracycline-containing chemotherapy experience improved relapse-free (RFS) and overall survival (OS) compared with those who receive non–anthracycline-containing chemotherapy. Such benefit, however, may be restricted to women whose tumors have specific molecular characteristics. We tested the hypothesis that HER2, epidermal growth factor receptor (EGFr)/HER1, HER3, Ki67, and topoisomerase IIα expression are predictive of outcome after anthracycline-based chemotherapy.

Methods

Tissue microarrays from 322 of 374 women in the BR9601 trial, which compared cyclophosphamide, methotrexate, and fluorouracil (CMF) with epirubicin followed by CMF (epi-CMF), were analyzed for HER1, 2, 3, 4; Ki67; and topoisomerase IIα protein expression and for HER2/topoisomerase IIα gene amplification. Their relationships to RFS and OS were investigated, and multiple regression analysis was used to identify interactions.

Results

A significant interaction was seen between tumors with normal HER1, HER2 fluorescent in situ hybridization (FISH), or HER3 levels and the enhanced benefit from epi-CMF versus CMF for RFS (hazard ratio [HR], 0.36; HR for overexpressed HER1 or HER2 FISH or HER3, 0.92; P = .035) and for OS (HR, 0.30; HR for overexpressed HER1 or HER2 FISH or HER3), 0.98; P = .023). Neither Ki67 nor TIIα expressions or gene alterations showed clear predictive value for benefit from the addition of the anthracycline.

Conclusion

Patients with HER2 amplified and those with HER1, HER2 FISH, or HER3-positive tumors did not benefit from the addition of epirubicin to CMF. Conversely, patients with HER2 nonamplified and HER1 through HER3–negative tumors showed significantly increased RFS and OS rates when treated with epi-CMF compared with CMF.
Matched Unrelated or Matched Sibling Donors Result in Comparable Survival After Allogeneic Stem-Cell Transplantation in Elderly Patients With Acute Myeloid Leukemia: A Report From the Cooperative German Transplant Study Group
Authors: Schetelig Johannes , Bornhäuser Martin , Schmid Christoph , Hertenstein Bernd , Schwerdtfeger Rainer , Martin Hans , Stelljes Matthias , Hegenbart Ute , Schäfer-Eckart Kerstin , Füssel Monika , Wiedemann Barbel , Thiede Christian , Kienast Joachim , Baurmann Herrad , Ganser Arnold , Kolb Hans Jochem , Ehninger Gerhard
Published: September 2008

Purpose

In patients with acute myeloid leukemia (AML), differential indications for matched sibling and unrelated hematopoietic stem-cell transplantation (HCT) are considered, and arbitrary age limits for HCT exist. We sought to determine whether donor type is a prognostic factor in elderly patients in the era of high-resolution DNA-based HLA typing.

Patients and Methods

We performed univariate and multivariate analyses of event-free survival (EFS) and overall survival (OS) in patients older than 50 years with standard- or high-risk AML who had received an allogeneic HCT between 1995 and 2005. Available DNA from donors and recipients of unrelated HCT was retyped so that the HLA-A, -B, -C, and -DRB1 alleles could be characterized in detail. Unrelated donors (UDs) were classified as matched (8/8), possibly matched (matched, but incomplete information), partially matched (one mismatch), or poorly matched (two or more mismatches) according to the final typing results.

Results

Data from 368 patients with a median age of 57 years (range, 50 to 73 years) were included. Multivariate Cox regression analysis revealed that patients’ disease status at HCT (P < .001) and the cytogenetic risk (P < .001) highly significantly predicted EFS and OS. Compared with patients with matched sibling donors, the adjusted relative risk of EFS was 0.7 (95% CI, 0.4 to 1.1) for patients with matched UDs and 1.0 (95% CI, 0.7 to 1.6) for patients with partially matched UDs.

Conclusion

Donor type is not a major prognostic factor for HCT in elderly patients with standard- or high-risk AML.
Somatic CEBPA Mutations Are a Frequent Second Event in Families With Germline CEBPA Mutations and Familial Acute Myeloid Leukemia
Authors: Pabst Thomas , Eyholzer Marianne , Haefliger Simon , Schardt Julian , Mueller Beatrice U.
Published: September 2008

Purpose

The transcription factor CCAAT/enhancer binding protein-α (CEBPA) is crucial for normal myeloid differentiation. Mutations in the CEBPA gene are found in subsets of patients with acute myeloid leukemia (AML). Recently, three families were reported in whom several family members had germline CEBPA mutations and subsequently developed AML. Whereas familial AML is considered a rare event, the frequency of CEBPA germline mutations in AML is not known.

Patients and Methods

In this study, we screened 187 consecutive AML patients for CEBPA mutations at diagnosis. We detected 18 patients (9.6%) with CEBPA mutations. We then analyzed remission samples and constitutive DNA from these patients.

Results

We found that two (11.1%) of 18 AML patients with CEBPA mutations carried a germline N-terminal frameshift CEBPA mutation. Interestingly, additional members in the families of both of these patients have been affected by AML, and the germline CEBPA mutations were also observed in these patients. Additional somatic mutations in AML patients with germline CEBPA mutations in the two families comprised in-frame C-terminal CEBPA mutations in two patients, two nonsilent CEBPA point mutations in one patient, and monosomy 7 in one patient.

Conclusion

This study shows, for the first time to our knowledge, that germline CEBPA mutations are frequently observed among AML patients with CEBPA mutations. Including the families with germline CEBPA mutations reported previously, additional somatic CEBPA mutations represent a frequent second event in AML with germline CEBPA mutations. Our data strongly indicate that germline CEBPA mutations predispose to AML and that additional somatic CEBPA mutations contribute to the development of the disease.
Phase III, Double-Blind Study of Depot Octreotide Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy: Results of North Central Cancer Treatment Group N00CA
Authors: Martenson James A. , Halyard Michele Y. , Sloan Jeff A. , Proulx Gary M. , Miller Robert C. , Deming Richard L. , Dick Stephen J. , Johnson Harold A. , Tai T.H. Patricia , Zhu Angela W. , Keit Joan , Stien Kathy J. , Atherton Pamela J.
Published: September 2008

Purpose

To assess the effectiveness of depot octreotide for the prevention of diarrhea during pelvic radiation therapy.

Patients and Methods

Patients receiving pelvic radiation therapy (planned minimum dose, 45 Gy; 1.7 to 2.1 Gy daily) were eligible for the study. From May 10, 2002, through October 14, 2005, 125 patients were randomly allocated in a double-blind fashion to receive octreotide (100 μg, administered subcutaneously on day 1, followed by depot octreotide, 20 mg, administered intramuscularly on days 2 and 29; n = 62) or to receive a placebo (n = 63).

Results

Grade 0, 1, 2, and 3 diarrhea were observed in 18%, 31%, 31%, and 21% of patients in the octreotide arm, respectively, and in 25%, 32%, 22%, and 21% of patients in the placebo arm, respectively (P = .64). Grade 0, 1, 2, and 3 abdominal cramps were observed in 32%, 45%, 21%, and 2% of patients receiving octreotide, respectively, and in 51%, 24%, 21%, and 5% of patients receiving the placebo, respectively (P = .053). Some patient-reported symptoms were worse in the octreotide group, including nocturnal bowel movements (70% v 45%; P = .004), clustering of bowel movements (90% v 69%; P = .004), and bleeding with bowel movements (57% v 35%; P = .01).

Conclusion

As administered in this study, octreotide did not decrease diarrhea during pelvic radiation therapy. Some gastrointestinal symptoms were worse in patients treated with octreotide. Octreotide is not indicated for prevention of diarrhea during pelvic radiation therapy.
The Effects of Central Adiposity on Growth Hormone (GH) Response to GH-Releasing Hormone-Arginine Stimulation Testing in Men
Authors: Makimura Hideo , Stanley Takara , Mun David , You Sung Min , Grinspoon Steven
Published: September 2008

Context: The relative contribution of central adiposity vs. weight on GH response to stimulation testing in obesity is not known.

Objective: We aimed to assess the contribution of weight and specific measures of central and peripheral adiposity to GH response to GHRH-arginine testing in lean, overweight, and obese men.

Design: A total of 75 men [mean age, 44.3 ± 1.1 yr; body mass index (BMI), 28.8 ± 0.7 kg/m2] were investigated. Subjects were classified as lean (BMI < 25 kg/m2; n = 23), overweight (BMI ≥ 25 and <30 kg/m2; n = 28), or obese (BMI ≥ 30 kg/m2; n = 24). Subjects were also stratified by waist circumference (WC) (<102 cm, n = 47; ≥102 cm, n = 28). Body composition and regional adiposity were assessed by anthropometrics, dual-energy x-ray absorptiometry (DEXA), and abdominal computed tomography (CT) scans.

Results: Peak stimulated GH was 36.4 ± 5.4, 16.6 ± 2.9, and 7.6 ± 0.9 μg/liter among lean, overweight, and obese subjects, respectively (P < 0.001 for all comparisons). Peak stimulated GH was 26.9 ± 3.4 μg/liter among subjects with WC less than 102 cm compared to 7.9 ± 0.9 μg/liter among subjects with WC of 102 cm or greater (P < 0.0001). Separate multivariate models using anthropometric, DEXA, and CT-derived measures of central adiposity demonstrated strong associations between peak stimulated GH and measures of central adiposity including WC, trunk fat by DEXA, and visceral adiposity by CT, controlling for age, BMI, and more general measures of adiposity. WC was independently associated with peak GH response to GHRH-arginine in a model including age, BMI, and hip circumference. In this model, BMI was no longer significant, and peak GH was reduced 1.02 μg/liter for each 1 cm increase in WC (P = 0.02).

Conclusions: GH response to GHRH-arginine testing is reduced in both overweight and obese subjects and negatively associated with indices of central abdominal obesity including WC, trunk fat, and visceral adipose tissue. The use of waist circumference, as a surrogate for central adiposity, adds predictive information to the determination of GH response, independent of BMI.
Teaching Circles
Authors: Marshall Margaret J.
Published: September 2008

This essay describes and critiques the creation and evolution of Teaching Circles, small groups of teachers meeting regularly to discuss curriculum and pedagogy, as a vehicle for teacher development in the composition program at the University of Miami. Included in the essay are comments from several of the full-time lecturers who participated in these discussion groups as both members and leaders. The essay makes visible the competing tensions inherent in fostering professional development through such a structure, especially the complications involved in turning lecturers into teacher educators as they take on responsibility for mentoring beginning teachers. The essay and the comments from the lecturers note the challenges inherent in making such an institutional structure productive over time and suggest that sustained critical reflection, willingness to revise, and attention to the scholarship of teaching teachers are important components of keeping any structure of professional development relevant.
Writing Program Administration and Faculty Professional Development
Authors: Willard-Traub Margaret K.
Published: September 2008

The author considers faculty development and its potential relationship to the ethos of collaborative practice modeled both by critical (Freirean) pedagogy and by interdisciplinary research. As a primary concern for any academic administrator, faculty development is not only a teaching moment but also an opportunity for reciprocal exchange, learning, and knowledge production, allowing participants to challenge the received wisdom of their fields and to come to a more rhetorical understanding of their identities. The collaborative construction of new knowledge and an emerging understanding of identities are examined in the context of two professional development and administrative contexts: the assessment by faculty of the writing of entering, first-year students and a collegewide, first-year experience (learning-community) initiative.
Rhetoricians, Facilitators, Models
Authors: Sidler Michelle
Published: September 2008

With the importance of online research, writing, and communication, computers are increasingly vital to instruction within the humanities. To help prepare teachers and administrators who engage with computerized instruction, this article examines faculty development through the lens of technology training by reporting on issues and concerns expressed by twelve technology trainers in a series of interviews. The interviewees provided their experiences and advice, including ways to approach institutional challenges, faculty participation, and pedagogical integrity. Most importantly, the author argues that technology training is a complex rhetorical activity involving a strong sense of kairos, context, and audience.
Interdisciplinary Work as Professional Development
Authors: Mullin Joan A.
Published: September 2008

This article explores, through the lens of a WAC faculty developer, how it is difficult to maintain disciplinary neutrality when developing any program; both teaching and learning can easily become codified through the lens of one person, field, or group. By using the work of, among others, Krista Ratcliffe, Mikhail Bakhtin, and David Bartholomae, I make a case for working differently with stakeholders: collaborating within a discipline and including students in faculty development plansas both learners and mentors. If we mutually examine our definitions (“teaching,” “learning,” “writing,” “students”) and engage in rhetorical and reflective listening, we can move away from a model of teaching as rules, templates, and regulations; we can begin to engage our own assumptions along with those of our students, changing together the very definitions that constrain the evolution of our own mutual development.
The Rhetorical Situation
Authors: Schneider Barbara
Published: September 2008

This article considers why, in the wake of Ernest Boyer's work, the promise of a transformation of university teaching has not been broadly realized and what that implies for faculty development projects. It discusses the assumptions that place the professional development of teaching outside of disciplinary boundaries, both literally and figuratively, and considers the consequences of that placement. It then turns to the scholarship of teaching and learning, considering what it offers to and implies about the disciplinary practices it proposes to transform. In response to this examination, the essay proposes that the Boyer Report attempted to alter teaching by arguing that teachers and the systems that support them needed to change, an argument that failed to convince college faculty to change. The article concludes with the proposal that the real exigence facing college faculty is that the way students raised in a culture saturated in electronic media learn is dramatically different than the way people learned a generation ago. That shift in learning is the exigence that requires a transformation of teaching.
Cautionary Tales
Authors: Donahue Tiane
Published: September 2008

It has become increasingly clear that U.S. faculty cannot afford to remain insular about global issues in teaching and the forces that are shaping them. At the same time, our desire to address or resist those issues, to join in or to find alternatives, needs to be contextualized. The three edited collections reviewed here address globalization of higher education in Australia, writing instruction in higher education in the United Kingdom, and interdisciplinary collaboration in U.S. higher education. The three bring different perspectives to current U.S. discussions of internationalization and interdisciplinary work in higher education and allow us to better understand issues in other cultures and disciplines while critically examining our own through new lenses.
Faculty Development in English Studies
Authors: Blalock Glenn
Published: September 2008

This overview of resources for faculty development initiatives in Englishstudies proposes a specific framework and sequence for faculty development work and identifies and annotates key resources. It proposes that the sequence for should take place within the theoretical framework of the learning paradigm, introduces faculty to the science of learning and teaching for significant learning, engages faculty in the scholarship of teaching and learning, and focuses on ways to create and maintain communities of practice and knowledge. Work on this overview initiated the development of an interactive Web-based clearinghouse devoted to the ongoing gathering and sharing of faculty development resources.
All muscle satellite cells are equal, but are some more equal than others?
Authors: Zammit Peter S.
Published: September 2008

Skeletal muscle is an accessible adult stem-cell model in which differentiated myofibres are maintained and repaired by a self-renewing stem-cell compartment. These resident stem cells, which are known as satellite cells, lie on the surface of the muscle fibre, between the plasmalemma and overlying basal lamina. Although they are normally mitotically quiescent in adult muscle, satellite cells can be activated when needed to generate myoblasts, which eventually differentiate to provide new myonuclei for the homeostasis, hypertrophy and repair of muscle fibres, or fuse together to form new myofibres for regeneration. Satellite cells also self-renew in order to maintain a viable stem-cell pool that is able to respond to repeated demand. The study of the control of self-renewal has led to the idea that the satellite-cell pool might be heterogeneous: that is it might contain both self-renewing satellite `stem' cells and myogenic precursors with limited replicative potential in the same anatomical location. The regulatory circuits that control satellite-cell self-renewal are beginning to be deciphered, with Pax7, and Notch and Wnt signalling being clearly implicated. This Commentary seeks to integrate these interesting new findings into the wider context of satellite-cell biology, and to highlight some of the many outstanding questions.
Clathrin-independent endocytosis of ErbB2 in geldanamycin-treated human breast cancer cells
Authors: Barr Daniel J. , Ostermeyer-Fay Anne G. , Matundan Rachel A. , Brown Deborah A.
Published: September 2008

The epidermal growth factor (EGF)-receptor family member ErbB2 is commonly overexpressed in human breast cancer cells and correlates with poor prognosis. Geldanamycin (GA) induces the ubiquitylation, intracellular accumulation and degradation of ErbB2. Whether GA stimulates ErbB2 internalization is controversial. We found that ErbB2 was internalized constitutively at a rate that was not affected by GA in SK-BR-3 breast cancer cells. Instead, GA treatment altered endosomal sorting, causing the transport of ErbB2 to lysosomes for degradation. In contrast to earlier work, we found that ErbB2 internalization occurred by a clathrin- and tyrosine-kinase-independent pathway that was not caveolar, because SK-BR-3 cells lack caveolae. Similar to cargo of the glycosylphosphatidylinositol (GPI)-anchored protein-enriched early endosomal compartment (GEEC) pathway, internalized ErbB2 colocalized with cholera toxin B subunit, GPI-anchored proteins and fluid, and was often seen in short tubules or large vesicles. However, in contrast to the GEEC pathway in other cells, internalization of ErbB2 and fluid in SK-BR-3 cells did not require Rho-family GTPase activity. Accumulation of ErbB2 in vesicles containing constitutively active Arf6-Q67L occurred only without GA treatment; Arf6-Q67L did not slow transport to lysosomes in GA-treated cells. Further characterization of this novel clathrin-, caveolae- and Rho-family-independent endocytic pathway might reveal new strategies for the downregulation of ErbB2 in breast cancer.