bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficiency of Type I IFN Receptor in Lupus-Prone New Zealand Mixed 2328 Mice Decreases Dendritic Cell Numbers and Activation and Protects from Disease
Authors: Agrawal Hemant , Jacob Noam , Carreras Esther , Bajana Sandra , Putterman Chaim , Turner Sean , Neas Barbara , Mathian Alexis , Koss Michael N. , Stohl William , Kovats Susan , Jacob Chaim O. 
Published: October 2009

Abstract
Type I IFNs are potent regulators of innate and adaptive immunity and are implicated in the pathogenesis of systemic lupus erythematosus. Here we report that clinical and pathological lupus nephritis and serum anti-nuclear Ab levels are greatly attenuated in New Zealand Mixed (NZM) 2328 mice deficient in type I IFN receptors (IFNAR). To determine whether the inflammatory environment in NZM 2328 mice leads to IFNAR-regulated changes in dendritic cells (DC), the number, activation, and function of DC subsets were compared in 2- and 5-mo-old (clinically healthy) female NZM and NZM-IFNAR−/− mice. Numbers of activated CD40high plasmacytoid DC (pDC) were significantly increased in renal lymph nodes of 2-mo-old NZM but not NZM-IFNAR−/− mice, suggesting an early IFNAR-dependent expansion and activation of pDC at disease sites. Relative to NZM spleens, NZM-IFNAR−/− spleens in 5-mo-old mice were significantly decreased in size and contained reduced numbers of conventional DC subsets, but not pDC. Splenic and renal lymph node NZM-IFNAR−/− DC analyzed directly ex vivo expressed significantly less CD40, CD86, and PDL1 than did NZM DC. Upon activation with synthetic TLR9 ligands in vitro, splenic NZM-IFNAR−/− DC produced less IL-12p40/70 and TNF-α than did NZM DC. The limited IFNAR−/− DC response to endogenous activating stimuli correlated with reduced numbers of splenic activated memory CD4+ T cells and CD19+ B cells in older mice. Thus, IFNAR signaling significantly increases DC numbers, acquisition of Ag presentation competence, and proinflammatory function before onset of clinically apparent lupus disease.
Microglial Activation by Citrobacter koseri Is Mediated by TLR4- and MyD88-Dependent Pathways
Authors: Liu Shuliang , Kielian Tammy 
Published: October 2009

Abstract
Citrobacter koseri is a Gram-negative bacterium that can cause a highly aggressive form of neonatal meningitis, which often progresses to establish multifocal brain abscesses. Despite its tropism for the brain parenchyma, microglial responses to C. koseri have not yet been examined. Microglia use TLRs to recognize invading pathogens and elicit proinflammatory mediator expression important for infection containment. In this study, we investigated the importance of the LPS receptor TLR4 and MyD88, an adaptor molecule involved in the activation of the majority of TLRs in addition to the IL-1 and IL-18 receptors, for their roles in regulating microglial activation in response to C. koseri. Proinflammatory mediator release was significantly reduced in TLR4 mutant and MyD88 knockout microglia compared with wild-type cells following exposure to either live or heat-killed C. koseri, indicating a critical role for both TLR4- and MyD88-dependent pathways in microglial responses to this pathogen. However, residual proinflammatory mediator expression was still observed in TLR4 mutant and MyD88 KO microglia following C. koseri exposure, indicating a contribution of TLR4- and MyD88-independent pathway(s) for maximal pathogen recognition. Interestingly, C. koseri was capable of surviving intracellularly in both primary microglia and macrophages, suggesting that these cells may serve as a reservoir for the pathogen during CNS infections. These results demonstrate that microglia respond to C. koseri with the robust expression of proinflammatory molecules, which is dictated, in part, by TLR4- and MyD88-dependent signals.
The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway
Authors: Zheng Yiyu T. , Shahnazari Shahab , Brech Andreas , Lamark Trond , Johansen Terje , Brumell John H. 
Published: October 2009

Abstract
Autophagy, a cellular degradative pathway, plays a key role in protecting the cytosol from bacterial colonization, but the mechanisms of bacterial recognition by this pathway are unclear. Autophagy is also known to degrade cargo tagged by ubiquitinated proteins, including aggregates of misfolded proteins, and peroxisomes. Autophagy of ubiquitinated cargo requires p62 (also known as SQSTM1), an adaptor protein with multiple protein-protein interaction domains, including a ubiquitin-associated (UBA) domain for ubiquitinated cargo binding and an LC3 interaction region (LIR) for binding the autophagy protein LC3. Previous studies demonstrated that the intracellular bacterial pathogen Salmonella typhimurium is targeted by autophagy during infection of host cells. Here we show that p62 is recruited to S. typhimurium targeted by autophagy, and that the recruitment of p62 is associated with ubiquitinated proteins localized to the bacteria. Expression of p62 is required for efficient autophagy of bacteria, as well as restriction of their intracellular replication. Our studies demonstrate that the surveillance of misfolded proteins and bacteria occurs via a conserved pathway, and they reveal a novel function for p62 in innate immunity.
CD47 and TLR-2 Cross-Talk Regulates Neutrophil Transmigration
Authors: Chin Alex C. , Fournier Bénédicte , Peatman Eric J. , Reaves Titus A. , Lee Winston Y. , Parkos Charles A. 
Published: October 2009

Abstract
Neutrophil (PMN) infiltration into tissues is a hallmark of acute inflammation and is crucial for the rapid removal of microbial pathogens. Previous studies have shown that PMN transmigration is regulated by the cell surface protein CD47. However this phenomenon in the context of microbial invasion and subsequent TLR signaling is poorly understood. In this study, we assessed the role of TLR2 and CD47 costimulation in regulating PMN transmigration. Human PMN transmigration across acellular collagen-coated filters toward the bacterial chemoattractant fMLP was more significantly inhibited by MALP-2 (TLR2/6 agonist) than Pam3CSK4 (TLR2/1 agonist). Subsequent experiments demonstrated that treatment with MALP-2 or anti-human CD47 mAbs delayed human PMN transfilter migration, while combined treatment led to further delayed inhibition. Interestingly, stimulation of PMNs with MALP-2 resulted in an increase in surface expression of CD11b, but not CD47. In experiments addressing the role of TLR agonists in regulating CD47-mediated PMN transmigration, incubation with MALP-2 or with anti-mouse CD47 mAbs did not inhibit transfilter migration of TLR2−/− or MyD88−/−-deficient murine bone marrow-derived PMNs. Similarly, inhibition of MyD88 homodimerization reversed the attenuation of human PMN transmigration induced by MALP-2 or anti-human CD47 mAbs. Separate experiments demonstrated that CD47−/− murine bone marrow-derived PMNs exhibited 4-fold decreased sensitivity toward MALP-2. Collectively, these findings suggest that activation of CD47 signaling enhances PMN sensitivity toward TLR2 activation which, in turn, signals their arrival at a site of invasion and may facilitate antimicrobial function.
Expulsion of Secondary Trichinella spiralis Infection in Rats Occurs Independently of Mucosal Mast Cell Release of Mast Cell Protease II
Authors: Blum Lisa K. , Thrasher Seana M. , Gagliardo Lucille F. , Fabre Valeria , Appleton Judith A. 
Published: October 2009

Abstract
Our aim was to elucidate the contribution of mucosal mast cells to the effector phase of a secondary immune response to Trichinella spiralis. During secondary infection, rats expel 90–99% of T. spiralis first-stage larvae from the intestine in a matter of hours. This phenomenon appears to be unique to rats and has been called rapid expulsion. Primary intestinal infection by T. spiralis induces mastocytosis, and mast cell degranulation occurs when challenged rats exhibit rapid expulsion. These observations have engendered the view that mast cells mediate rapid expulsion. In this study, we report that. immunization of adult Albino Oxford rats by an infection limited to the muscle phase did not induce intestinal mastocytosis, yet such rats exhibited rapid expulsion when challenged orally. Although mastocytosis was absent, the protease unique to mucosal mast cells, rat mast cell protease II (RMCPII), was detected in sera at the time of expulsion. We further evaluated mast cell activity in neonatal rats that display rapid expulsion. Pups born to infected dams displayed rapid expulsion, and RMCPII was detected in their sera. By feeding pups parasite-specific mAbs or polyclonal Abs before challenge infection, it was possible to dissociate mast cell degranulation from parasite expulsion. These results indicate that rapid expulsion can occur in the absence of either intestinal mastocytosis or RMCPII release. Furthermore, release of RMCPII is not sufficient to cause expulsion. The data argue against a role for mast cells in the mechanism underlying the effector phase of protective immunity against T. spiralis in rats.
Regulation of Gastric B Cell Recruitment Is Dependent on IL-17 Receptor A Signaling in a Model of Chronic Bacterial Infection
Authors: Algood Holly M. Scott , Allen Shannon Sedberry , Washington Mary K. , Peek Richard M. , Miller Geraldine G. , Cover Timothy L. 
Published: October 2009

Abstract
Th17-driven immune responses contribute to the pathogenesis of many chronic inflammatory diseases. In this study, we investigated the role of IL-17 signaling in chronic gastric inflammation induced by Helicobacter pylori, a Gram-negative bacterium that persistently colonizes the human stomach. Wild-type C57BL/6 mice and mice lacking IL-17RA (IL-17RA−/−) were orogastrically infected with H. pylori. Differences in bacterial colonization density and gastric inflammation were not apparent at 1 mo postinfection, but by 3 mo postinfection, H. pylori colonization density was higher and mononuclear gastric inflammation more severe in infected IL-17RA−/− mice than in infected wild-type mice. A striking feature was a marked increase in gastric B cells, plasma cells, and lymphoid follicles, along with enhanced H. pylori-specific serum Ab responses, in infected IL-17RA−/− mice. Fewer gastric neutrophils and lower levels of neutrophil-recruiting chemokines were detected in infected IL-17RA−/− mice than in infected wild-type mice. Gastric IL-17a and IL-21 transcript levels were significantly higher in infected IL-17RA−/− mice than in infected wild-type mice or uninfected mice, which suggested that a negative feedback loop was impaired in the IL-17RA−/− mice. These results underscore an important role of IL-17RA signaling in regulating B cell recruitment. In contrast to many chronic inflammatory diseases in which IL-17RA signaling promotes an inflammatory response, IL-17RA signaling down-regulates the chronic mononuclear inflammation elicited by H. pylori infection.
Human Cathelicidin Peptide LL-37 Modulates the Effects of IFN-γ on APCs
Authors: Nijnik Anastasia , Pistolic Jelena , Wyatt Aaron , Tam Sheena , Hancock Robert E. W. 
Published: October 2009

Abstract
The human cathelicidin peptide LL-37 is a multifunctional immunomodulatory and antimicrobial host defense peptide of the human immune system. LL-37 modulates host cell responses to microbial stimuli and also affects the action of other endogenous immune mediators such as IL-1β and GM-CSF. This activity of LL-37 is known to be complex, with the functional outcomes being dependent on the cell type and activation status, timing of exposure, and other immune mediators present. It was demonstrated in this study that LL-37 inhibited cellular responses to IFN-γ, the key cytokine of Th1-polarized immunity. The inhibitory activity of LL-37 on IFN-γ responses was characterized in monocytes, macrophages, dendritic cells, and B lymphocytes, showing suppression of cell activation, proliferation, and production of proinflammatory and Th1-polarizing cytokines, and Abs. It was further shown that in monocytes the suppressive effects of LL-37 were mediated through inhibition of STAT1-independent signaling events, involving both the p65 subunit of NF-κB and p38 MAPK. This study suggests that LL-37 modulates IFN-γ responses during both the innate and adaptive phases of immune responses, indicating a new immunomodulatory role for this endogenous peptide. These effects on IFN-γ activity should be taken into consideration in the development of cathelicidin-based peptides for therapeutic applications as immunomodulatory or microbicidal agents.
Doxorubicin-induced cardiotoxicity in adult Indian patients on chemotherapy
Authors: Khattry Navin , Malhotra Pankaj , Grover Anil , Sharma Suresh K , Varma Subhash 
Published: October 2009

Abstract
Background:Doxorubicin-induced cardiotoxicity is widely known to occur at cumulative doses exceeding 450 mg/m2 . However, very few studies have reported incidence of cardiac dysfunction in patients on chemotherapy with lower cumulative doses. To the best of our knowledge, there is no study carried out so far that has reported the incidence of cardiac dysfunction in adult Indian patients receiving doxorubicin. This study was undertaken to determine the incidence of doxorubicin-induced cardiotoxicity by serial resting echocardiography in patients on chemotherapy and identify risk factors associated with cardiotoxicity.Materials and Methods:Patients that were started on doxorubicin-based chemotherapy in the period from January 2000 to June 2001 and had completed at least 300 mg/m2cumulative dose were taken in the study. Electrocardiography, chest X-ray and echocardiography were done at baseline, at 300 mg/m2and at 450 mg/m2cumulative doses of doxorubicin. All patients were evaluated for the presence of the following risk factors:Age>70 years, female sex, preexisting cardiac disease, hypertension, chest wall irradiation, body mass index (BMI)< 20 kg/m2 , Karnofsky performance status, combination chemotherapy with cyclophosphamide and presence of liver disease. Subclinical cardiac dysfunction was defined as ejection fraction fall greater than 10% on follow-up echocardiography.Results:Thirty patients satisfied the criterion for being considered for evaluation. One (3%) patient developed congestive cardiac failure, while 8 (27%) patients developed subclinical cardiac dysfunction. Concomitant use of cyclophosphamide significantly increased the risk of cardiac dysfunction ( P=0.048), while low BMI (< 20 kg/m2 ) and preexisting cardiac disease showed a trend towards increased risk of cardiac dysfunction ( P=0.07 for both).Conclusion:Twenty-seven percent of the patients developed subclinical cardiac dysfunction in the cumulative dose range of 300-450 mg/m2 . This entails regular monitoring for cardiac dysfunction by echocardiography during treatment.
Ovarian lymphoma
Authors: Crasta Julian A , Vallikad Elizabeth 
Published: October 2009

AbstractThe involvement of the ovary in lymphomatous processes is rare. Such an involvement can occur in 2 ways, either primary or secondary, which usually presents with abdominal or pelvic complaints. We present a case of secondary involvement of the ovary with occult extra-ovarian nodal disease and discuss the histogenesis of ovarian lymphomas with criteria for diagnosis and differential diagnosis.
Melorheostosis with renal arterio-venous malformation: A case report with review of literature
Authors: Lone Abdul Rashid , Ahmad Mushtaq , Aziz Sheikh Aejaz , Bhat Gul Mohammad , Bhat Javid Rasool , Jahan Rifat , Khan Shoukat H 
Published: October 2009

AbstractMelorheostosis, also known as Leri′s disease and flowing periosteal hyperostosis, is a rare cause of pain and stiffness in a limb. The appearance is of "candle greasing" down one side of one or several bones of the body. We describe a case referred to tertiary care center with suspicion of renal cell carcinoma with diffuse bone metastasis. After reassessment, the patient was diagnosed melorheostosis with renal AV malformation. He was reassured about the benign nature of the disease and is asymptomatic.
Thermochemical Nanolithography of Multifunctional Nanotemplates for Assembling Nano‐Objects
Authors: Wang Debin , Kodali Vamsi K. , Underwood II William D. , Jarvholm Jonas E. , Okada Takashi , Jones Simon C. , Rumi Mariacristina , Dai Zhenting , King William P. , Marder Seth R. , Curtis Jennifer E. , Riedo Elisa 
Published: October 2009

AbstractNanoscale chemical patterning of different chemical species (amine, thiol, aldehyde, and biotin) in independent nanopatterns is achieved by the iterative application of thermochemical nanolithography (TCNL) to inscribe amine patterns followed by their chemical conversion to other functional groups. Due to the unique chemical stability of the patterns, the resultant substrates can be stored for weeks and subsequently be used for covalent and molecular‐recognition‐based attachment of nano‐objects using standard chemical protocols. In particular, the ability of this method to attach proteins and DNA to the chemical nanopatterns and to create co‐patterns of two distinctive bioactive proteins is demonstrated.
Efficiency Enhancement in Organic Photovoltaic Cells: Consequences of Optimizing Series Resistance
Authors: Servaites Jonathan D. , Yeganeh Sina , Marks Tobin J. , Ratner Mark A. 
Published: October 2009

AbstractHere, means to enhance power conversion efficiency (PCE or η) in bulk‐heterojunction (BHJ) organic photovoltaic (OPV) cells by optimizing the series resistance (Rs)—also known as the cell internal resistance—are studied. It is shown that current state‐of‐the‐art BHJ OPVs are approaching the limit for which efficiency can be improved via Rs reduction alone. This evaluation addresses OPVs based on a poly(3‐hexylthiophene):6,6‐phenyl C61‐butyric acid methyl ester (P3HT:PCBM) active layer, as well as future high‐efficiency OPVs (η > 10%). A diode‐based modeling approach is used to assess changes in Rs. Given that typical published P3HT:PCBM test cells have relatively small areas (∼0.1 cm2), the analysis is extended to consider efficiency losses for larger area cells and shows that the transparent anode conductivity is then the dominant materials parameter affecting Rs efficiency losses. A model is developed that uses cell sizes and anode conductivities to predict current–voltage response as a function of resistive losses. The results show that the losses due to Rs remain minimal until relatively large cell areas (>0.1 cm2) are employed. Finally, Rs effects on a projected high‐efficiency OPV scenario are assessed, based on the goal of cell efficiencies >10%. Here, Rs optimization effects remain modest; however, there are now more pronounced losses due to cell size, and it is shown how these losses can be mitigated by using higher conductivity anodes.
Complementary and alternative medicine use among long‐term lymphoma survivors: A pilot study
Authors: Habermann Thomas M. , Thompson Carrie A. , LaPlant Betsy R. , Bauer Brent A. , Janney Carol A. , Clark Matthew M. , Rummans Teresa A. , Maurer Matthew J. , Sloan Jeff A. , Geyer Susan M. , Cerhan James R. 
Published: October 2009

AbstractNo published survey has specifically addressed the beliefs, knowledge, and usage of complementary and alternative medicine (CAM) in long‐term (5–20 years) lymphoma survivors alone. In this pilot project, 95 subjects were randomly selected from a population of 2,475 long‐term lymphoma survivors and mailed a questionnaire. The median time from lymphoma diagnosis to completion of the questionnaire was 11 years (range 6–20). Overall, 68% (95% CI: 54–80%) of the long‐term lymphoma survivors reported that they have used CAM, a rate higher than the estimated usage rate reported for the general population The most commonly used modalities were chiropractic (39%, 95% CI: 27–53%) and massage therapy (21%, 95% CI: 12–34%). Less than 10% used meditation (5%, 95% CI: 1–15%) and relaxation (7%, 95% CI: 2–17%). In terms of common herbal usage, 5% (95% CI: 1–15%) had used St. John's Wort and 7% (95% CI: 2–17%) had used shark cartilage. Although none of the patients reported that CAM usage was directed specifically towards treating their lymphoma, 4% (95% CI: 0–12%) of patients reported that CAM could cure cancer, and 14% (95% CI: 6–26%) reported that CAM could increase their feeling of control over their health. This pilot study suggests that long‐term lymphoma survivors appear to use CAM at a rate higher than the general population. The use of potential agents of risk by the survivors and the lack of access to potentially beneficial modalities highlights the need for further study of CAM in this population. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.
Outcome of 93 patients with relapse or progression following allogeneic hematopoietic cell transplantation
Authors: Kurosawa Saiko , Fukuda Takahiro , Tajima Kinuko , Saito Bungo , Fuji Shigeo , Yokoyama Hiroki , Kim Sung‐Won , Mori Shin‐Ichiro , Tanosaki Ryuji , Heike Yuji , Takaue Yoichi 
Published: October 2009

AbstractRelapse/progression after allogeneic hematopoietic cell transplantation (allo‐HCT) remains the major cause of treatment failure. In this study, the subsequent clinical outcome was overviewed in 292 patients with leukemia/myelodysplastic syndrome who received allo‐HCT. Among them, 93 (32%) showed relapse/progression. Cohort 1 was chosen to receive no interventions with curative intent (n = 25). Cohort 2 received reinduction chemotherapy and/or donor lymphocyte infusion (n = 48), and Cohort 3 underwent a second allo‐HCT (n = 20). Sixty‐three patients received reinduction chemotherapy, and 27 (43%) achieved subsequent complete remission (CR). The incidence of nonrelapse mortality (NRM) was similar among the three cohorts (4, 15, and 5%). The 1‐year overall survival (OS) after relapse was significantly better in patients with a second HCT (58%) than in others (14%, Cohorts 1 and 2; P <.001). However, the 2‐year OS did not differ between the two groups, which suggests that it is difficult to maintain CR after the second HCT. Multivariate analysis showed that reinduction chemotherapy, CR after intervention, second HCT, and longer time to post‐transplant relapse were associated with improved survival. In conclusion, for patients with relapse after allo‐HCT, successful reinduction chemotherapy and a second HCT may be effective for prolonging survival without excessive NRM. However, effective measures to prevent disease progression after a second HCT clearly need to be developed. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.
Polymorphisms of drug‐metabolizing genes and risk of non‐Hodgkin lymphoma
Authors: Kim Hee Nam , Kim Nan Young , Yu Li , Kim Yeo‐Kyeoung , Lee Il‐Kwon , Yang Deok‐Hwan , Lee Je‐Jung , Shin Min‐Ho , Park Kyeong‐Soo , Choi Jin‐Su , Kim Hyeoung‐Joon 
Published: October 2009

AbstractDrug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug‐metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non‐Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population‐based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR)AG = 0.67, 95% confidence interval (CI) = 0.55–0.82; ORAG/GG = 0.66, 95% CI = 0.54–0.80) and DLBCL (ORAG = 0.63, 95% CI = 0.49–0.82; ORAG/GG = 0.64, 95% CI = 0.50–0.82). For T‐cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (ORAG/GG = 0.65, 95% CI = 0.44–0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (ORAG = 1.28, 95% CI = 1.07–1.54; ORAG/GG = 1.26, 95% CI = 1.06–1.51) and DLBCL (ORAG = 1.32, 95% CI = 1.04–1.66; ORAG/GG = 1.30, 95% CI = 1.03–1.63), but not T‐cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.