bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase II study of SGN‐30 (anti‐CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma
Authors: Forero‐Torres Andres , Leonard John P. , Younes Anas , Rosenblatt Joseph D. , Brice Pauline , Bartlett Nancy L. , Bosly Andre , Pinter‐Brown Lauren , Kennedy Dana , Sievers Eric L. , Gopal Ajay K. 
Published: May 2009

SummarySGN‐30, a chimeric anti‐CD30 monoclonal antibody, has demonstrated potent preclinical antitumour activity in both Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). We conducted an open‐label, Phase II study to determine the safety and objective response rate of SGN‐30 in 79 patients with refractory/recurrent HL (n = 38) or systemic ALCL (n = 41). Each course of SGN‐30 comprised 6 weekly intravenous infusions, followed by a 2‐week treatment‐free period. Patients had received a median of 3 (range 1–5) prior regimens of chemotherapy or systemic therapy. The initial 40 patients received 6 mg/kg weekly; the latter 39 patients received 12 mg/kg weekly. In the ALCL group, two patients achieved a complete response and five additional patients achieved a partial response, with response durations ranging from 27 to 1460+ d. No objective responses were observed in the HL group; however, 11 patients (29%) had stable disease (duration 62–242 days). Although adverse events were common, most were mild or moderate, and no specific pattern of adverse events was observed in either disease group. These results demonstrate that weekly administration of SGN‐30 is safe, with modest clinical activity in patients with ALCL.
NF‐E2 overexpression delays erythroid maturation and increases erythrocyte production
Authors: Mutschler Manuel , Magin Angela S. , Buerge Martina , Roelz Roland , Schanne Daniel H. , Will Britta , Pilz Ingo H. , Migliaccio Anna Rita , Pahl Heike L. 
Published: May 2009

SummaryThe transcription factor Nuclear Factor‐Erythroid 2 (NF‐E2) is overexpressed in the vast majority of patients with polycythaemia vera (PV). In murine models, NF‐E2 overexpression increases proliferation and promotes cellular viability in the absence of erythropoietin (EPO). EPO‐independent growth is a hallmark of PV. We therefore hypothesized that NF‐E2 overexpression contributes to erythrocytosis, the pathognomonic feature of PV. Consequently, we investigated the effect of NF‐E2 overexpression in healthy CD34+ cells. NF‐E2 overexpression led to a delay in erythroid maturation, manifested by a belated appearance of glycophorin A‐positive erythroid precursors. Maturation delay was similarly observed in primary PV patient erythroid cultures compared to healthy controls. Protracted maturation led to a significant increase in the accumulated number of erythroid cells both in PV cultures and in CD34+ cells overexpressing NF‐E2. Similarly, NF‐E2 overexpression altered erythroid colony formation, leading to an increase in erythroid burst‐forming unit formation. These data indicate that NF‐E2 overexpression delays the early phase of erythroid maturation, resulting in an expansion of erythroid progenitors, thereby increasing the number of erythrocytes derived from one CD34+ cell. These data propose a role for NF‐E2 in mediating the erythrocytosis of PV.
The bronchial response to mannitol is attenuated by a previous methacholine test: but not vice versa
Authors: Gade E. , Thomsen S. F. , Porsbjerg C. , Backer V. 
Published: May 2009

SummaryAim
To examine the airway response to inhaled mannitol performed before or after a methacholine challenge test in a group of asthmatics with different levels of disease.Methods
A total of 48 asthmatics, 18–73 years of age, were included in the study. Two pairs of challenges were performed in a random order on two separate days 24 h apart: either with mannitol performed first on day one, followed 1 h by methacholine, and methacholine as the first on day two, followed 1 h by mannitol or vice versa. A questionnaire‐based interview was performed and lung function, exhaled nitric oxide, skin prick test, and blood eosinophil count were measured.Results
A total of 44% of the asthmatics used inhaled corticosteroids and 48% were atopic. The airway response to mannitol was attenuated when mannitol was given after methacholine, compared with the response to mannitol when it was given first [log response dose ratio (RDR): 1.42 vs. 1.60 (P=0.004)], whereas the response to methacholine was unchanged in the opposite test order [log RDR: 0.81 vs. 0.96 (P=0.102)].Conclusion
Bronchial challenges with inhaled mannitol and methacholine may be performed on the same day but provocation with mannitol should be performed before methacholine.
Homeostatic chemokines CCL19 and CCL21 promote inflammation in human immunodeficiency virus-infected patients with ongoing viral replication
Authors: Damås J K , Landrø L , Fevang B , Heggelund L , Tjønnfjord G E , Fløisand Y , Halvorsen B , Frøland S S , Aukrust P 
Published: May 2009

SummaryCCL19 and CCL21 and their receptor CCR7 are expressed constitutively within lymphoid organs, regulating lymphocyte homing. Recent studies suggest that these chemokines may have inflammatory properties. We hypothesized a role of CCL19/CCL21 in human immunodeficiency virus (HIV) infection by promoting inflammation. We examined the expression of CCL19 and CCL21 in mononuclear cells from peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) in HIV-infected patients before and during highly active anti-retroviral therapy (HAART). We also examined the ability of CCL19/CCL21 to promote inflammatory responses in these patients. PBMC from untreated HIV-infected patients (n = 29) released enhanced levels of CCL19 spontaneously compared with cells from controls (n = 20), particularly in those with symptomatic disease (n = 15, P &lt; 0·01 versus controls). During HAART (n = 9), there was a decrease in the spontaneous CCL19 release and an increase in the phytohaemagglutinin-stimulated CCL19 release in both PBMC (P &lt; 0·01) and BMMC (P &lt; 0·05). In patients with enhanced HIV replication there was an increased proportion of inflammatory CD8+CCR7-CD45RA- T cells in peripheral blood [P &lt; 0·01 and P &lt; 0·05 versus controls, untreated (n = 9) and treatment failure (n = 8), respectively]. In vitro, CCL19/CCL21 promoted an inflammatory response in PBMC when accompanied by high viral load, irrespective of HAART. The HIV-tat protein significantly boosted the inflammatory effect of CCL19/CCL21 in PBMC. These findings link a dysregulated CCL19/CCL21/CCR7 system in HIV-infected patients to persistent inflammation and HIV replication, not only in untreated HIV infection, but also in treatment failure during HAART.
Translational Mini-Review Series on B Cell-Directed Therapies: B cell-directed therapy for autoimmune diseases
Authors: Hu C , Wong F S , Wen L 
Published: May 2009

SummaryB cells play an important role in the pathogenesis of both systemic and organ-specific autoimmune diseases. Autoreactive B cells not only produce autoantibodies, but are also specialized to present specific autoantigens efficiently to T cells. Furthermore, these B cells can secrete proinflammatory cytokines and can amplify the vicious cycle of self-destruction. Thus, B cell-directed therapies are potentially an important approach for treating autoimmune diseases. On the other hand, like T cells, there are subsets of B cells that produce anti-inflammatory cytokines and are immunosuppressive. These regulatory B cell subsets can protect against and ameliorate autoimmune diseases. Thus targeting B cells therapeutically will require this balance to be considered. Here we summarize the roles of pathogenic and regulatory B cells and current applications of B cell-directed therapy in autoimmune diseases. Considerations for future development of B cell-directed therapy for autoimmune diseases have also been discussed.
Translational Mini-Review Series on B Cell-Directed Therapies: The pathogenic role of B cells in autoantibody-associated autoimmune diseases – lessons from B cell-depletion therapy
Authors: Leandro M J , De La Torre I 
Published: May 2009

Summary
B cell depletion therapy with rituximab (BCDT) is a licensed treatment for rheumatoid arthritis and has shown promising results in the treatment of severe, refractory patients with other autoantibody-associated autoimmune diseases (AAID). The exact role that B cells play in the pathogenesis of AAID and consequently the mechanisms by which BCDT is effective are not known. The two more widely discussed hypotheses are that BCDT is effective because it removes the precursors of plasma cells producing pathogenic autoantibody species, or because it depletes a critical mass of autoreactive B cell clones that present antigen to pathogenic autoreactive T cells. This review will focus on the effects of BCDT and whether the response of patients with AAID to BCDT could be due ultimately to its effects on autoantibodies. A better knowledge of the main role that B cells play in the pathogenesis of the different diseases and a better understanding of the most likely mechanism of relapse following an earlier response to BCDT would help to guide further developments of B cell targeting therapies and potentially increase the chance of designing a protocol that could induce a long-term remission.
Translational Mini-Review Series on B Cell-Directed Therapies: Recent advances in B cell-directed biological therapies for autoimmune disorders
Authors: Levesque M C 
Published: May 2009

Summary
B cell-directed therapies are promising treatments for autoimmune disorders. Besides targeting CD20, newer B cell-directed therapies are in development that target other B cell surface molecules and differentiation factors. An increasing number of B cell-directed therapies are in development for the treatment of autoimmune disorders. Like rituximab, which is approved as a treatment for rheumatoid arthritis (RA), many of these newer agents deplete B cells or target pathways essential for B cell development and function; however, many questions remain about their optimal use in the clinic and about the role of B cells in disease pathogenesis. Other therapies besides rituximab that target CD20 are the furthest along in development. Besides targeting CD20, the newer B cell-directed therapies target CD22, CD19, CD40–CD40L, B cell activating factor belonging to the TNF family (BAFF) and A proliferation-inducing ligand (APRIL). Rituximab is being tested in an ever-increasing number of autoimmune disorders and clinical studies of rituximab combined with other biological therapies are being pursued for the treatment of rheumatoid arthritis (RA). B cell-directed therapies are being tested in clinical trials for a variety of autoimmune disorders including RA, systemic lupus erythematosus (SLE), Sjögren’s syndrome, vasculitis, multiple sclerosis (MS), Graves' disease, idiopathic thrombocytopenia (ITP), the inflammatory myopathies (dermatomyositis and polymyositis) and the blistering skin diseases pemphigus and bullous pemphigoid. Despite the plethora of clinical studies related to B cell-directed therapies and wealth of new information from these trials, much still remains to be discovered about the pathophysiological role of B cells in autoimmune disorders.
Dentists’ involvement in identification and reporting of child physical abuse: Jordan as a case study
Authors: OWAIS ARWA ISSA NOOR , QUDEIMAT MUAWIA ABDALLAH , QODCEIH SADEQ 
Published: May 2009

Objectives.  The objectives of this study were to assess the knowledge, attitude, and experience among Jordanian dentists regarding child abuse, and to explore the factors that affect their hesitation to report any suspected cases.Materials and methods.  A self‐administered structured questionnaire was sent randomly to 500 Jordanian dentists. It investigated dentists’ knowledge, attitude, and experience in recognizing and reporting child abuse cases. It also investigated several factors associated with dentists’ hesitation to report suspected cases of child physical abuse.Results.  The response rate was 68%. More dentists were aware of their ethical obligations (80%) than their legal responsibilities (71%) to report child abuse cases. One‐third of the dentists knew where to report suspected cases. Although 42% of dentists suspected cases of child abuse, only 20% of them reported these cases. The most frequently cited reasons for hesitation to report such cases were lack of history (76%), uncertainty about diagnosis (73%), and possible consequences on the child (66%). Reporting was significantly associated with suspicion of child abuse cases, as well as the belief of legal responsibilities.Conclusion.  There was a low reporting rate of child abuse among Jordanian dentists. They lack the adequate knowledge about recognition and reporting issues of suspected cases.
Management of ecological thresholds to re‐establish disturbance‐maintained herbaceous wetlands of the south‐eastern USA
Authors: Martin Katherine L. , Katherine Kirkman L. 
Published: May 2009

Summary1. The restoration of disturbance‐maintained ecosystems may require management to overcome ecological thresholds and re‐establish feedbacks that perpetuate an alternative community. We use hardwood‐dominated depression wetlands (locally known as oak domes) embedded in the fire‐maintained longleaf pine–wiregrassPinus palustris–Aristida strictaecosystem as an example where concepts developed from alternative state theory are applied to practical restoration.2. As extant communities were not available as reference sites, we based our restoration objectives on knowledge of vegetation dynamics, land‐use history and historical data. We quantified a hardwood encroachment pattern beginning with the establishment of central nuclei during fire‐free periods. Expansion of this core of hardwoods is positively reinforced by the accumulation of fuels that impede the spread of fire.3. In order to examine the feasibility of re‐establishing herbaceous communities, we selected 10 depression wetlands in 2000 and randomly assigned a hardwood removal treatment to half of them. During the transition period of fine fuel accumulation, we adapted the management regime as necessary for control of hardwood re‐sprouts and to promote the development of a fire‐maintained community.4. After 5 years, hardwood removal communities had shifted toward herbaceous dominance, characterized by multi‐layered, species‐rich, native, wetland‐specific ground flora. The rapid recovery of herbaceous species was probably possible because of initial seedling recruitment from a persistent wetland soil seed bank. This immediate recruitment of herbaceous vegetation produced fine fuels, allowing for the reintroduction of frequent prescribed fire and, thus, the re‐establishment of the herbaceous community‐fire feedback mechanism necessary to maintain the community state.5. Synthesis and applications. Our findings confirm that it is possible to re‐establish a rare alternative community state in a fire‐maintained ecosystem. Establishment of a desired transition trajectory required decoupling ecological feedbacks that inhibit reintroduction of fire while facilitating positive feedbacks to promote fire. Our approach incorporating ecological thresholds and biotic legacies, such as a persistent seed bank, can serve as a model to inform restoration strategies for other disturbance‐maintained ecosystems.
Pseudomonas chlororaphis strain JF3835 reduces mortality of juvenile perch, Perca fluviatilis L., caused by Aeromonas sobria
Authors: Gobeli S , Goldschmidt‐Clermont E , Frey J , Burr S E 
Published: May 2009

AbstractMotile aeromonad septicaemia caused by Aeromonas sobria is a cause of disease in farmed perch, Perca fluviatilis L., in Switzerland. We have evaluated the potential of a Pseudomonas chlororaphis isolate, obtained from perch intestine, to control A. sobria infection. Inoculation of juvenile perch with P. chlororaphis strain JF3835 prior to infection with A. sobria caused a reduction in A. sobria associated mortalities. Infection of perch with xylE‐labelled P. chlororaphis indicated the bacterium is able to transiently colonize juvenile fish and fingerlings.
A simple non‐enzymatic method for the preparation of white spot syndrome virus (WSSV) DNA from the haemolymph of Marsupenaeus japonicus using FTA matrix cards
Authors: Sudhakaran R , Mekata T , Kono T , Supamattaya K , Linh N T H , Suzuki Y , Sakai M , Itami T 
Published: May 2009

AbstractWhite spot syndrome virus (WSSV) is an important shrimp pathogen responsible for large economic losses for the shrimp culture industry worldwide. The nucleic acids of the virus must be adequately preserved and transported from the field to the laboratory before molecular diagnostic analysis is performed. Here, we developed a new method to isolate WSSV‐DNA using Flinders Technology Associates filter paper (FTA matrix card; Whatman) without centrifugation or hazardous steps involved. FTA technology is a new method allowing the simple collection, shipment and archiving of nucleic acids from haemolymph samples providing DNA protection against nucleases, oxidation, UV damage, microbial and fungal attack. DNA samples prepared from 10‐fold dilutions of moribund shrimp haemolymph using FTA matrix cards were analysed using semi‐quantitative and quantitative polymerase chain reaction (PCR) and were compared with two commercially available DNA isolation methods, the blood GenomicPrep Mini Spin Kit (GE Healthcare) and the DNAzol (Invitrogen). Sequence analysis was performed for the DNA samples prepared using the various isolation procedures and no differences in the sequence among these methods were identified. Results based on the initial copy number of DNA prepared from the GenomicPrep Mini Spin Kit are a little more sensitive than the DNA prepared from FTA matrix cards, whereas the DNAzol method is not suitable for blood samples. Our data shows the efficiency of retention capacity of WSSV‐DNA samples from impregnated FTA matrix cards. Matrix cards were easy to store and ship for long periods of time. They provide ease of handling and are a reliable alternative for sample collection and for molecular detection and characterization of WSSV isolates.
The high‐molecular‐mass amylase (HMMA) of Geobacillus stearothermophilus ATCC 12980 interacts with the cell wall components by virtue of three specific binding regions
Authors: Ferner‐Ortner‐Bleckmann Judith , Huber‐Gries Carina , Pavkov Tea , Keller Walter , Mader Christoph , Ilk Nicola , Sleytr Uwe B. , Egelseer Eva M. 
Published: May 2009

SummaryThe complete nucleotide sequence encoding the high‐molecular‐mass amylase (HMMA) of Geobacillus stearothermophilus ATCC 12980 was established by PCR techniques. Based on the hmma gene sequence, the full‐length rHMMA, four N‐ or C‐terminal rHMMA truncations as well as three C‐terminal rHMMA fragments were cloned and heterologously expressed in Escherichia coli. Purified rHMMA forms were used either for affinity studies with the recombinant (r) S‐layer protein SbsC (rSbsC), peptidoglycan‐containing sacculi (PGS) and pure peptidoglycan (PG) devoid of the secondary cell wall polymer (SCWP), or for surface plasmon resonance (SPR) studies using rSbsC and isolated SCWP. In the C‐terminal part of the HMMA, three specific binding regions, one for each cell wall component (rSbsC, SCWP and PG), could be identified. The functionality of the PG‐binding domain could be confirmed by replacing the main part of the SCWP‐binding domain of an S‐layer protein by the PG‐binding domain of the HMMA. The present work describes a completely new and highly economic strategy for cell adhesion of an exoenzyme.
Impact of genetic polymorphisms on the pathogenesis of achalasia: an age‐dependent paradigm?
Authors: Sarnelli Giovanni 
Published: May 2009

Abstract A wealth of evidence supports the concept that achalasia represents an autoimmune disorder in which a triggering factor (probably a virus) is the starter of an uncontrolled myenteric ganglionitis leading to neurodegeneration. The reasons whereby this process occurs only in some individuals and at the oesophageal level are unknown, but it is reasonable to assume that some genetic influence may affect the achalasia phenotype, making some individuals more or less susceptible to the disease. Association studies between achalasia and polymorphisms of genes involved in the regulation of immune responses may help to explain the complexity of achalasia pathogenesis and progression.
Pioglitazone decreases postprandial accumulation of remnant lipoproteins in insulin‐resistant smokers
Authors: Abbasi F. , Lamendola C. , Leary E. T. , Reaven G. M. 
Published: May 2009

Background:  Fasting hypertriglyceridaemia has been reported to occur commonly in cigarette smokers and is thought to increase cardiovascular disease (CVD) risk in these individuals. More recently, it has been suggested that an increase in non‐fasting triglycerides, rather than fasting hypertriglyceridaemia, is an independent CVD risk factor.Methods:  In this study, we divided 24 smokers into insulin‐resistant (IR) and insulin‐sensitive (IS) groups by determining their steady‐state plasma glucose concentrations during the insulin suppression test and compared fasting and daylong postprandial accumulation of total triglycerides and remnant lipoprotein (RLP) concentrations, before and after 3 months of pioglitazone (PIO) administration.Results:  The two groups were similar in age, body mass index, race and gender distribution, but differed dramatically in insulin sensitivity. Baseline fasting and postprandial triglyceride, RLP cholesterol and RLP triglyceride concentrations were significantly higher in the IR smokers (p = 0.01 to <0.01). Insulin sensitivity and both fasting and postprandial triglyceride and RLP triglyceride levels decreased significantly (p = 0.05 to <0.01) in PIO‐treated IR smokers, without any significant increase in weight. In contrast, there were no significant changes in either insulin sensitivity or fasting and postprandial triglyceride, RLP cholesterol and RLP triglyceride levels in PIO‐treated IS smokers.Conclusions:  The postprandial accumulation of RLP particles is increased in the IR subset of smokers and is likely to contribute to the increased CVD risk in these individuals. Furthermore, PIO administration provides a possible therapeutic approach to decreasing postprandial lipaemia and CVD risk in IR smokers who are unwilling or unable to stop smoking.