bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma
Authors: Polson Andrew G. , Yu Shang-Fan , Elkins Kristi , Zheng Bing , Clark Suzanna , Ingle Gladys S. , Slaga Dionysos S. , Giere Lynne , Du Changchun , Tan Christine , Hongo Jo-Anne , Gogineni Alvin , Cole Mary J. , Vandlen Richard , Stephan Jean-Philippe , Young Judy , Chang Wesley , Scales Suzie J. , Ross Sarajane , Eaton Dan , Ebens Allen 
Published: March 2007

AbstractTargeting cytotoxic drugs to cancer cells using antibody–drug conjugates (ADCs), particularly those with stable linkers between the drug and the antibody, could be an effective cancer treatment with low toxicity. However, for stable-linker ADCs to be effective, they must be internalized and degraded, limiting potential targets to surface antigens that are trafficked to lysosomes. CD79a and CD79b comprise the hetrodimeric signaling component of the B-cell receptor, and are attractive targets for the use of ADCs because they are B-cell–specific, expressed in non-Hodgkin lymphomas (NHL), and are trafficked to a lysosomal-like compartment as part of antigen presentation. We show here that the stable-linker ADCs anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are capable of target-dependent killing of nonHodgkin lymphoma cell lines in vitro. Further, these 2 ADCs are equally effective as low doses in xenograft models of follicular, mantle cell, and Burkitt lymphomas, even though several of these cell lines express relatively low levels of CD79b in vivo. In addition, we demonstrate that anti-CD79b ADCs were more effective than anti-CD79a ADCs and that, as hypothesized, anti-CD79b antibodies downregulated surface B-cell receptor and were trafficked to the lysosomal-like major histocompatibility complex class II–positive compartment MIIC. These results suggest that anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are promising therapeutics for the treatment of NHL.
BRAF V600E Maintains Proliferation, Transformation, and Tumorigenicity of BRAF-Mutant Papillary Thyroid Cancer Cells
Authors: Liu Dingxie , Liu Zhi , Condouris Stephen , Xing Mingzhao 
Published: March 2007

Abstract
Context: Although the BRAF V600E mutant can initiate the formation of papillary thyroid cancer (PTC), it is unclear whether it is required to maintain cell proliferation, transformation, and tumor growth of BRAF mutation-harboring PTC.
Objective: The aim of the study was to investigate whether BRAF V600E is required for the proliferation, transformation, and tumorigenicity of BRAF mutation-harboring PTC cells.
Design: We addressed this issue using BRAF small interference RNA (siRNA) to transfect stably several BRAF mutation-harboring PTC cell lines, isolated clones with stable suppression of BRAF, and assessed their ability to proliferate, transform, and grow xenograft tumors in nude mice.
Results: PTC cell proliferation and transformation were suppressed in specific BRAF siRNA clones, but not in control scrambled siRNA clones. Specifically, taking the advantage of stable BRAF knockdown, we were able to show continued suppression of PTC cell proliferation and transformation, or anchorage-independent colony formation in soft agar, after long-term culture. Moreover, we also demonstrated that in vivo tumorigenicity and growth of tumors from the specific BRAF siRNA cell clones in nude mice were suppressed compared with control clones.
Conclusions: BRAF V600E is not only an initiator of PTC as demonstrated previously but is also a maintainer of proliferation, transformation, and tumorigenicity of PTC cells harboring BRAF mutation, and growth of tumors derived from such cells continues to depend on BRAF V600E. These results provide further support for potentially effective therapy targeted at BRAF for BRAF mutation-harboring PTC.
Interactions among Peroxisome Proliferator Activated Receptor-γ, Insulin Signaling Pathways, and Steroidogenic Acute Regulatory Protein in Human Ovarian Cells
Authors: Seto-Young Donna , Avtanski Dimiter , Strizhevsky Marina , Parikh Grishma , Patel Parini , Kaplun Julia , Holcomb Kevin , Rosenwaks Zev , Poretsky Leonid 
Published: March 2007

AbstractContext and Objective: Peroxisome proliferator activated receptor-γ (PPAR-γ) agonists thiazolidinediones (TZDs) are thought to ameliorate hyperandrogenism in polycystic ovary syndrome by reducing hyperinsulinemia. However, TZDs also exhibit direct effects in the human ovary. We examined interactions among PPAR-γ, insulin signaling pathways, and steroidogenic acute regulatory (StAR) protein in human ovarian cells.Materials and Methods: Mixed human ovarian tissue culture that contained granulosa, theca, and stromal cells, and a culture of purified granulosa cells obtained during in vitro fertilization, were established as previously described. Cells were cultured in the presence or absence of insulin, with or without 25 or 50 μm rosiglitazone or pioglitazone. Expression of PPAR-γ, insulin receptor, or insulin receptor substrate (IRS)-1 in both cell systems and of the StAR protein in granulosa cells was measured using immunoprecipitation and immunoblotting.Results: Rosiglitazone stimulated expression of PPAR-γ, insulin receptor α- and β-subunits, and IRS-1 up to 168% (P &lt; 0.05), 679% (P &lt; 0.006), 290% (P &lt; 0.037), and 323% (P &lt; 0.01) of baseline, respectively. Pioglitazone stimulated expression of PPAR-γ, insulin receptor α- and β-subunits, and IRS-1 up to 222% (P &lt; 0.01), 362% (P &lt; 0.001), 402% (P &lt; 0.029), and 492% (P &lt; 0.03), respectively. Insulin alone stimulated expression of PPAR-γ, α-subunit and β-subunit of insulin receptor, and IRS-1 up to 174% (P &lt; 0.001), 692% (P &lt; 0.014), 275% (P &lt; 0.024), and 431% (P &lt; 0.01), respectively. In purified granulosa cell culture, rosiglitazone stimulated expression of StAR protein up to 540% (P &lt; 0.007), and pioglitazone stimulated expression of StAR protein up to 670% (P &lt; 0.007). Insulin alone stimulated expression of StAR protein up to 600% (P &lt; 0.012).Conclusions: Insulin and TZDs independently stimulate expression of PPAR-γ, insulin receptor, IRS-1, and StAR protein in human ovarian cells. Thus, PPAR-γ, insulin receptor with its signaling pathways, and StAR protein constitute a novel human ovarian regulatory system with complex interactions among its components.
The Calcium-Sensing Receptor Is a Target of Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1
Authors: Gavalas Nikos G. , Kemp E. Helen , Krohn Kai J. E. , Brown Edward M. , Watson Philip F. , Weetman Anthony P. 
Published: March 2007

Abstract
Context: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder caused by mutations in the autoimmune regulator gene. Hypoparathyroidism occurs in 80% of patients with APS1 and has been suggested to result from an autoimmune reaction against the calcium-sensing receptor (CaSR) on parathyroid cells. However, the detection of CaSR antibodies in APS1 remains controversial, with some studies disputing the relevance of the receptor as an autoantigen.
Objective: The aim of this study was to analyze a defined set of APS1 patient sera for the presence of CaSR antibodies using different assay systems.
Results: APS1 patients and individuals with other autoimmune disorders along with healthy subjects were tested for antibody binding to the CaSR. In an immunoprecipitation assay with the CaSR expressed in human embryonic kidney 293 cells, 12 of 14 (85.7%) APS1 and two of 28 (7.1%) Graves’ disease patients were considered positive for CaSR antibodies. The prevalence of receptor antibodies was significantly greater than that in the cohort of healthy individuals only in the APS1 patient group (P &lt; 0.0001). In a flow cytometry assay, seven of 14 (50.0%) APS1 patient sera showed binding to the extracellular domain of the CaSR. The prevalence of receptor antibodies in the APS1 patient group was significantly greater than that in the group of healthy controls (P = 0.023). No CaSR antibodies could be detected in any patients or controls using a radiobinding assay.
Conclusion: The CaSR is an autoantigen in APS1, but detection of antibodies against the receptor appears to be influenced by the assay system used.
Age of Onset of Type 1 Diabetes in Children and Carotid Intima Medial Thickness
Authors: Dalla Pozza Robert , Bechtold Susanne , Bonfig Walter , Putzker Stefanie , Kozlik-Feldmann Rainer , Netz Heinrich , Schwarz Hans-Peter 
Published: March 2007

Abstract
Context: Cardiovascular disease due to atherosclerosis is a major cause of morbidity and mortality in adult diabetic patients. In children, signs of subclinical atherosclerosis such as increased intima-media thickness (IMT) of the common carotid arteries have been detected in several studies. However, concerns may arise about the different analyzing methods used because measurements in patients and controls differ significantly.
Patients and Methods: We studied 208 children [150 patients with diabetes mellitus type 1, mean age (±sd) 13.9 ± 2.8 yr, 66 males, mean glycosylated hemoglobin (±sd) 7.8 ± 1.4%, and 58 healthy controls, mean age (±sd) 14.1 ± 3.1 yr, 32 males] and used normal IMT values published recently for comparison of the results.
Results: Of 150 patients, 37 had an increased IMT [mean IMT (±sd) 1.6 ± 0.6], whereas healthy controls had nearly normal IMT values [mean IMT (±sd) 0.3 ± 0.1; P &lt; 0.001]. Age at onset of diabetes, mean daily insulin dosage, systolic blood pressure, and total cholesterol level were significantly related to IMT in a multilinear regression model. A total of 25 diabetic patients were hypertensive and had a significantly increased IMT (mean IMT 0.475 ± 0.03 mm) compared to the remaining patients (mean IMT 0.459 ± 0.02 mm; P &lt; 0.05).
Conclusions: The IMT measurement detected subclinical atherosclerosis in a large cohort of diabetic children. Systolic blood pressure, total cholesterol level, insulin dosage, and age at onset of the disease were significantly related to the IMT. Longitudinal measurements may help to identify patients at special risk for atherosclerotic changes and cardiovascular disease.
Comparative roles of Twist-1 and Id1 in transcriptional regulation by BMP signaling
Authors: Hayashi Masanori , Nimura Keisuke , Kashiwagi Katsunobu , Harada Taku , Takaoka Kunio , Kato Hiroyuki , Tamai Katsuto , Kaneda Yasufumi 
Published: March 2007

Basic helix-loop-helix (bHLH) transcription factors are known as key regulators for mesenchymal differentiation. The present study showed that overexpression of Twist-1, a bHLH transcription factor, suppresses bone morphogenetic protein (BMP)-induced osteoblast differentiation, and downregulation of endogenous Twist-1 enhances BMP signaling. Maximal inhibition of BMP signaling was observed when Twist-1 was bound to E47, which markedly enhanced the stability of Twist-1. Co-immunoprecipitation assays revealed that Twist-1 formed a complex with Smad4 and histone deacetylase (HDAC) 1 in MC3T3-E1 cells stably expressing Twist-1. With trichostatin, an HDAC inhibitor, osteogenic factors such as alkaline phosphatase, Runx2 and osteopontin increased. Those results suggested that Twist-1 inhibited BMP signaling by recruiting HDAC1 to Smad4.Furthermore, the inhibitory effects of Twist-1 on BMP signaling were overcome by Id1 through induction of Twist-1 degradation. These findings suggest that Twist-1 can act as an inhibitor of BMP signaling, and Id1 can regulate BMP signaling through a positive feedback loop repressing Twist-1 function. These two molecules may therefore regulate differentiation of mesenchymal cells into progeny such as osteoblasts by controlling BMP signaling.
Organizing Pneumonia and Pulmonary Eosinophilic Infiltration Associated with Daptomycin
Authors: Cobb Elizabeth , Kimbrough Robert C , Nugent Kenneth M , Phy Michael P 
Published: March 2007

Objective:To report a case of organizing pneumonia with pulmonary eosinophilic infiltrates in a patient receiving daptomycin.Case Summary:An 84-year-old man developed bilateral, irregularly shaped nodules and infiltrates in the mid and peripheral lung and multiple mediastinal lymph nodes following treatment with intravenous daptomycin for infection of his left knee prosthesis. His other symptoms included decreased appetite, weight loss (6.8 kg over 4–6 wk), malaise, and generalized weakness after 4 weeks of daptomycin therapy. Transthoracic needle biopsy revealed organizing pneumonia with scattered eosinophils. His symptoms and results of computed tomography (CT) scan improved in the month following discontinuation of daptomycin. The Naranjo probability scale indicated a probable reaction to daptomycin.Discussion:Pulmonary reactions have been reported with numerous drugs and have a wide range of clinical and radiographic presentations. Clinical trials have shown that daptomycin is well tolerated and has an adverse effect profile similar to that of vancomycin and the semisynthetic penicillins. This case report suggests that chronic use of daptomycin caused organizing pneumonia with eosinophilic infiltrates in a patient treated for an infected knee prosthesis. A definite mechanism for this reaction is not known. We speculate that the chronic administration of daptomycin allowed drug accumulation in surfactant in the alveolar spaces. This may result in higher concentrations of drug near the alveolar epithelial surface, which could injure the epithelium, resulting in organizing pneumonia.Conclusions:Development of new pulmonary infiltrates in patients treated with chronic daptomycin therapy should alert healthcare workers to this potential association.
Quetiapine and Breast Feeding
Authors: Rampono Jonathan , Kristensen Judith H , Ilett Kenneth F , Hackett L Peter , Kohan Rolland 
Published: March 2007

Objective: To quantify the relative infant dose of quetiapine during breast feeding, describe the milk:plasma (M:P) ratio, and determine the well-being of the exposed infant. Case Summary: A 26-year-old mother and her 3-month-old son were studied over a 24 hour quetiapine dose interval at steady-state. Quetiapine concentrations were quantified by high-performance liquid chromatography. Infant exposure was calculated as the concentration in milk multiplied by an estimated milk production of 0.15 L/kg/day and normalized to the weight-adjusted maternal dose. The average concentration in milk was 41 μg/L, the M:P ratio (measured using average concentrations in the elimination phase) was 0.29, and the relative infant dose was 0.09% of the maternal weight-adjusted dose (7273 μg/kg/day). The infant plasma concentration of 1.4 μg/L was some 6% of the corresponding maternal plasma concentration. No adverse effects were noted in the infant. Discussion: Our findings of an infant exposure to quetiapine of less than 0.1% of the maternal dose and a lack of adverse effects confirm and extend the findings of 2 previous studies. Conclusions: Although limited, the data shown here support the prescription of quetiapine to a breast-feeding mother following a careful individual risk/benefit analysis. We suggest regular monitoring of infant progress and occasional measurement of quetiapine in the infant's plasma.
Interstitial Nephritis Secondary to Bevacizumab Treatment in Metastatic Leiomyosarcoma
Authors: Barakat Ruchdi K , Singh Navneet , Lal Rajiv , Verani Regina R , Finkel Kevin W , Foringer John R 
Published: March 2007

Objective: To report a case of interstitial nephritis associated with the administration of bevacizumab. Case Summary: A 26-year-old man diagnosed with metastatic rectal leiomyosarcoma was treated with intravenous bevacizumab 5 mg/kg and received a total of 3 doses at 2 week intervals. His creatinine had increased from 1.0 mg/dL at baseline to 1.6 mg/dL after 2 doses of bevacizumab and to 4.7 mg/dL after the third dose, prompting admission. Acute renal failure was diagnosed, and hemodialysis was initiated. A renal biopsy revealed interstitial nephritis. Renal failure resolved with cessation of the drug, and the patient did not require further hemodialysis. Discussion: Bevacizumab is a recombinant humanized monoclonal immunoglobulin G antibody to vascular endothelial growth factor. Bevacizumab has shown efficacy in treatment of patients with renal cell carcinoma and colorectal cancer and has been approved by the Food and Drug Administration as a first-line treatment for metastatic colorectal cancer. Our patient had no other confounding factors that might have caused renal failure. The presence of primary glomerular disease was excluded by biopsy. According to the Naranjo probability scale, bevacizumab was the probable cause of acute renal failure in this patient. Conclusions: Bevacizumab can cause acute renal failure by inducing interstitial nephritis. Renal function should be monitored during bevacizumab therapy.
Hospital Policies for Treatment of Acute Decompensated Heart Failure
Authors: Vats Vikrant , Didomenico Robert J , Wojtynek Jeffrey E , Theobald John C , Schumock Glen T 
Published: March 2007

Background: It is unclear to what extent hospitals use guidelines or protocols in treating acute decompensated heart failure (ADHF) and whether nesiritide is included in these guidelines or protocols. Objective: To assess the formulary status of currently used drugs, therapeutic guidelines, and perceptions about the appropriateness of treatment of ADHF in community hospitals. Methods: A Web-based survey of pharmacy directors at community hospitals that were part of a national group purchasing organization was conducted. Results: One hundred seven hospitals participated in the survey (response rate 47.1%). Diuretics such as furosemide and bumetanide were more commonly included (100% and 94.4%, respectively) on hospital formularies than was torsemide (69.2%). Dopamine and dobutamine were more common (94.4% each) on the formulary than was milrinone (68.2%), Nitroprusside and nitroglycerin were listed on the formularies of more than 90% of participating institutions, while nesiritide was listed on the formularies in only 48.6% of hospitals and was placed on restricted status in 36.4% of hospitals. Guidelines for care of patients with ADHF were used in the emergency department (ED), inpatient care units, and outpatient clinics in 18.6%, 43.0%, and 8.5% of hospitals, respectively. Overall, ADHF care, including general treatment as well as specific use of nesiritide, was deemed appropriate in the majority of patients, but nearly twice as many respondents perceived the management of ADHF and specific use of nesiritide as inappropriate in the ED compared with inpatient treatment. Only 41.1% of the respondents reported following Braunwald recommendations for the use of nesiritide. Conclusions: A sizable percentage of responding community hospitals do not have guidelines for treatment of ADHF despite the existence of such guidelines in the literature. There are opportunities for improvement in the general treatment of ADHF as well as for the use of nesiritide in ADHF, especially in the ED or observation unit versus inpatient units.
Educational psychology and the effectiveness of inclusive education/mainstreaming
Authors: Lindsay Geoff 
Published: March 2007

Background. Inclusive education/mainstreaming is a key policy objective for the education of children and young people with special educational needs (SEN) and disabilities.Aims. This paper reviews the literature on the effectiveness of inclusive education/mainstreaming. The focus is on evidence for effects in terms of child outcomes with examination also of evidence on processes that support effectiveness.Samples. The review covers a range of SEN and children from pre‐school to the end of compulsory education.Method. Following an historical review of evidence on inclusive education/mainstreaming, the core of the paper is a detailed examination of all the papers published in eight journals from the field of special education published 2001‐2005 (N=1373): Journal of Special Education, Exceptional Children, Learning Disabilities Research and Practice, Journal of Learning Disabilities, Remedial and Special Education, British Journal of Special Education, European Journal of Special Needs Education, and the International Journal of Inclusive Education. The derived categories were: comparative studies of outcomes: other outcome studies; non‐comparative qualitative studies including non‐experimental case studies; teacher practice and development; teacher attitudes; and the use of teaching assistants.Results. Only 14 papers (1.0%) were identified as comparative outcome studies of children with some form of SEN. Measures used varied but included social as well as educational outcomes. Other papers included qualitative studies of inclusive practice, some of which used a non‐comparative case study design while others were based on respondent's judgements, or explored process factors including teacher attitudes and the use of teaching assistants.Conclusions. Inclusive education/mainstreaming has been promoted on two bases: the rights of children to be included in mainstream education and the proposition that inclusive education is more effective. This review focuses on the latter issue. The evidence from this review does not provide a clear endorsement for the positive effects of inclusion. There is a lack of evidence from appropriate studies and, where evidence does exist, the balance was only marginally positive. It is argued that the policy has been driven by a concern for children's rights. The important task now is to research more thoroughly the mediators and moderators that support the optimal education for children with SEN and disabilities and, as a consequence, develop an evidence‐based approach to these children's education.
Zur Bartók-Rezeption in Russland
Authors: Tschigareva Evgenia 
Published: March 2007

Abstract
Béla Bartók's sympathies towards Russian culture are well-known, as is the veneration of the Hungarian master by Russian musicians. During the course of three quarters of a century the image of Bartók the composer and folklore researcher has gradually infolded itself to Russian musical circles as well as the broad strata of music lowers. This thesis presents an integral overview of the reception of Bartók in Russia: the perception of his musical legacy by composers, musicological research about him, performances and publications of his works in Russia, comments from the press, and of music critics, etc. At the same time a particular evolution could be traced: an active interest towards Bartók the composer and pianist in the 1920s, then a nearly twenty-five years “pause;” in the 1950's a perception of him primarily as a folklor researcher as well as a progressive musical public figure at that an aversion from the official policy makers of his musical style as an “avant-garde” style during the dominance of the doctrine of “socialist realism;” the discovery of Bartók's innovative style, his influence on the young Soviet composers (E. Denisov, A. Schnittke, S. Gubaidulina) during the 1960's and 1970's; an overall comprehensive study of his musical legacy and the recognition of his significance (1960's–1980's), a decline of interest towards Bartók (as a classic) as a result of the stream of information, gushing from the West, having to do with the “new music” of the avant-garde of the “second wave” and the “post-avantgarde” trends (during the 1990's); a resurgence of interest at the turn of the century and an acquiescence of Bartók's artistic path as being perspective for musical art.