tbuckley/cabot-search huggingface dataset:
Targeting Receptor-Mediated Transport for Delivery of Biologics Across the Blood-Brain Barrier
Authors: Jason M. Lajoie, Eric V. Shusta
Journal: The Annual Review of Pharmacology and Toxicology (2014)

Biologics are an emerging class of medicines with substantial promise to treat neurological disorders such as Alzheimer's disease, stroke, and multiple sclerosis. However, the blood-brain barrier (BBB) presents a formidable obstacle that appreciably limits brain uptake and hence the therapeutic potential of biologics following intravenous administration. One promising strategy for overcoming the BBB to deliver biologics is the targeting of endogenous receptor-mediated transport (RMT) systems that employ vesicular trafficking to transport ligands across the BBB endothelium. If a biologic is modified with an appropriate targeting ligand, it can gain improved access to the brain via RMT. Various RMT-targeting strategies have been developed over the past 20 years, and this review explores exciting recent advances, emphasizing studies that show brain targeting in vivo.
Canine cardiac sarcolemmal vesicles demonstrate rapid initial Na(+)-Ca2+ exchange activity.
Authors: C L Gruver, A M Katz, F C Messineo
Journal: Circulation Research (1990)

To identify a rapid, uninhibited rate of exchange activity, we investigated in canine sarcolemmal vesicles the rapid kinetics of Na(+)-Ca2+ exchange. Sarcolemmal vesicles were incubated in 160 mM NaCl and 20 mM HEPES at 25 degrees C (pH 7.4) and actively loaded with 45Ca2+ for 2 minutes by Na(+)-Ca2+ exchange. After further uptake was inhibited by dilution into 0.15 mM Na(+)-free EGTA, sarcolemmal vesicles were immobilized on a rapid filtration apparatus that allowed millisecond resolution of 45Ca2+ fluxes. In the presence of external NaCl (Na+o) but not other monovalent cations (i.e., K+, Li+), a biphasic pattern of Ca2+ release was observed--an initial brief and rapid rate of Ca2+ release followed by a second slower, prolonged phase of Ca2+ release. Semilogarithmic plots of sarcolemmal Ca2+ content versus time were not linear but were consistent with a biexponential rate of Na+o-induced Ca2+ release during the first several seconds of the exchange reaction. The fast phase of Na+o-stimulated Ca2+ release was several thousand-fold more rapid than that in the absence of Na+o. Both phases of Ca2+ release showed a similar Na+o dependence (Km, approximately 12 mM) with evidence of a positive cooperative effect of Na+. Vmax of the fast and slow phases were approximately 37.0 and approximately 0.76 nmol/mg/sec, respectively. Using rapid-reaction techniques, we demonstrated in the present study that the initial velocity of sarcolemmal Na(+)-Ca2+ exchange activity is greater than previously reported in sarcolemmal vesicles and that this exchange process exhibits complex rate behavior with a biphasic pre-steady state kinetic pattern.
Production of interleukin 10 by islet cells accelerates immune-mediated destruction of beta cells in nonobese diabetic mice.
Authors: L Wogensen, M S Lee, N Sarvetnick
Journal: The Journal of Experimental Medicine (1994)

The T helper type 2 (Th2) cell product interleukin 10 (IL-10) inhibits the proliferation and function of Th1 lymphocytes and macrophages (M phi). The nonobese diabetic mouse strain (NOD/Shi) develops a M phi and T cell-dependent autoimmune diabetes that closely resembles human insulin-dependent diabetes mellitus (IDDM). The objective of the present study was to explore the consequences of localized production of IL-10 on diabetes development in NOD/Shi mice. Surprisingly, local production of IL-10 accelerated the onset and increased the prevalence of diabetes, since diabetes developed at 5-10 wk of age in 92% of IL-10 positive I-A beta g7/g7, I-E- mice in first (N2) and second (N3) generation backcrosses between IL-10 transgenic BALB/c mice and (NOD/Shi) mice. None of the IL-10 negative major histocompatibility complex-identical littermates were diabetic at this age. Furthermore, diabetes developed in 33% of I-A beta g7/d, I-E+ N3 mice in the presence of IL-10 before the mice were 10 wk old. Our findings support the notion that IL-10 should not simply be regarded as an immunoinhibitory cytokine, since it possesses powerful, immunostimulatory properties as well. Furthermore, our observations suggest that beta cell destruction in NOD mice may be a Th2-mediated event.
Definition and constituents of maltreatment in sport: establishing a conceptual framework for research practitioners
Authors: A E Stirling
Journal: British Journal of Sports Medicine (2008)

There has recently been an increased emergence of research on the maltreatment of athletes in sport. It is suggested that research may play a particularly salient role with respect to athlete protection initiatives. However, as it stands, current research in this area is limited by a lack of consistency in definitions. The purpose of the paper, therefore, is to propose a conceptual framework of maltreatment in sport to be used among research practitioners. More specifically, a conceptual model of the different categories, constructs and constituents of maltreatment in sport is proposed. Sport-specific examples of the various maltreatments are outlined. Current literature is reviewed, and recommendations are made for future research.
Randomized Controlled Phase Ib Study of Ghrelin Agonist, RM-131, in Type 2 Diabetic Women With Delayed Gastric Emptying
Authors: Andrea Shin, Michael Camilleri, Irene Busciglio, Duane Burton, Elizabeth Stoner, Patrick Noonan, Keith Gottesdiener, Steven A. Smith, Adrian Vella, Alan R. Zinsmeister
Journal: Diabetes Care (2012)

To investigate the pharmacokinetics (PK), pharmacodynamics, and safety of single-dose RM-131 in type 2 diabetic patients with gastrointestinal cardinal symptoms (GCSI) and previously documented delayed gastric emptying (DGE).In a randomized crossover study, 10 female patients received RM-131 (100 μg s.c.) or placebo and underwent scintigraphic gastric emptying (GE) and colonic filling at 6 h (CF6) of a solid-liquid meal administered 30 min postdosing. Adverse events, plasma glucose, and hormonal levels were assessed. GCSI daily diary (GCSI-DD) was completed during treatments. PK was assessed in this cohort and healthy volunteers (HVs).At screening, HbA(1c) was 7.2 ± 0.4% (SEM) and total GCSI-DD score was 1.32 ± 0.21. RM-131 accelerated GE t(1/2) of solids (P = 0.011); mean difference (Δ) in solid GE t(1/2) was 68.3 min (95% CI 20-117) or 66.1%. There were numerical differences in GE lag time, CF6 solids, and GE t(1/2) liquids (all P < 0.14). With a significant (P < 0.014) order effect, further analysis of the first treatment period (n = 5 per group) confirmed significant RM-131 effects on GE t(1/2) (solids, P = 0.016; liquids, P = 0.024; CF6, P = 0.013). PK was similar in DGE patients and HVs. There were increases in 120-min blood glucose (P = 0.07) as well as 30-90-min area under the curve (AUC) levels of growth hormone, cortisol, and prolactin (all P < 0.02) with single-dose RM-131. Only light-headedness was reported more on RM-131.RM-131 greatly accelerates the GE of solids in patients with type 2 diabetes and documented DGE. PK is similar in diabetic patients and HVs.
A review of instruments to assess illness representations in patients with rheumatic diseases: Table 1
Authors: M Maas, E Taal, S van der Linden, A Boonen
Journal: Annals of the Rheumatic Diseases (2009)

Objective: Critical appraisal of instruments to assess illness representations in rheumatology. Methods: A first search (MEDLINE, EMBASE, PsycINFO) identified articles describing development of instruments assessing illness representations. A second search identified articles applying them in rheumatology. Appraisal was performed using checklists. Results: Five instruments were identified: the Illness Perception Questionnaire (IPQ), the Revised Illness Perception Questionnaire (IPQ-R), the Illness Cognition Questionnaire (ICQ), the Implicit Models of Illness Questionnaire (IMIQ) and the Meaning of Illness Questionnaire (MIQ). The number of items varied from 18 to 70. Internal consistency was good. Construct validity was moderate to good for all instruments, but was not tested for the IMIQ. Predictive validity was assessed for the ICQ and IPQ and was low to moderate. Sensitivity to change was tested for ICQ and was good. Applications in rheumatology are increasing. Significant relationships with different outcomes and additional evidence for predictive validity were found. Conclusions: Five instruments that assess illness representations can be used in rheumatology. The number of subscales and items vary. The ICQ and IPQ are most extensively validated and have been most frequently applied in rheumatology. Illness representations have relevant associations with self-report and objective outcomes. They should be considered when exploring health in rheumatology.
Detection and prediction of acute heart transplant rejection with the myocardial T2determination provided by a black-blood magnetic resonance imaging sequence
Authors: Pierre Y Marie, Michael Angioı̈, Jean P Carteaux, Jean M Escanye, Sophie Mattei, Kiril Tzvetanov, Olivier Claudon, Nathalie Hassan, Nicolas Danchin, Gilles Karcher, Alain Bertrand, Paul M Walker, Jean P Villemot
Journal: Journal of the American College of Cardiology (2001)
Biology, prognosis and response to therapy of breast carcinomas according to HER2 score
Authors: S. Ménard, A. Balsari, E. Tagliabue, T. Camerini, P. Casalini, R. Bufalino, F. Castiglioni, M.L. Carcangiu, A. Gloghini, S. Scalone, P. Querzoli, M. Lunardi, A. Molino, M. Mandarà, M. Mottolese, F. Marandino, M. Venturini, C. Bighin, G. Cancello, E. Montagna, F. Perrone, A. De Matteis, A. Sapino, M. Donadio, N. Battelli, A. Santinelli, L. Pavesi, A. Lanza, F.A. Zito, A. Labriola, R.A. Aiello, M. Caruso, F. Zanconati, G. Mustacchi, M. Barbareschi, M. Frisinghelli, R. Russo, G. Carrillo
Journal: Annals of Oncology (2008)
Decreased Energy Reserve in an Animal Model of Dilated Cardiomyopathy
Authors: Ronglih Liao, Luigino Nascimben, Jan Friedrich, Judith K. Gwathmey, Joanne S. Ingwall
Journal: Circulation Research (1996)

Abstract An animal model was used to test the hypothesis that in heart failure the decrease in the ability to resynthesize ATP through the creatine kinase (CK) reaction (which we call energy reserve) contributes to the inability of the heart to maintain its normal function and contractile reserve. One-week-old turkey poults were fed furazolidone for 14 days to induce dilated cardiomyopathy. Isolated Langendorff-perfused hearts from these myopathic animals showed a 73% decrease in baseline isovolumic contractile performance. Neither increasing [Ca 2+ ] o nor electrical pacing rate increased isovolumic contractile performance. Measured by 31 P nuclear magnetic resonance magnetization transfer and chemical assay, ATP concentration was decreased by 23%, phosphocreatine concentration by 42%, CK enzyme activity by 34%, and the pseudo first-order rate constant for the CK reaction by 50%. Measured CK reaction velocity decreased by 71%. The reduced ability to increase cardiac performance in response to increasing [Ca 2+ ] o in hearts with lower CK reaction velocity was reproduced in part by feeding a separate group of turkey poults β-guanidinopropionic acid to specifically reduce CK reaction velocity by decreasing guanidino substrate concentration. These hearts had normal baseline performance but blunted contractile reserve. These observations provide further support for the hypothesis that a decrease in energy reserve via the CK system contributes to reduced cardiac function in the failing heart.
Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study
Authors: Nicholas M. Douglas, Daniel A. Lampah, Enny Kenangalem, Julie A. Simpson, Jeanne R. Poespoprodjo, Paulus Sugiarto, Nicholas M. Anstey, Ric N. Price
Journal: PLoS Medicine (2013)

Ric Price and colleagues use hospital-based surveillance data to estimate the risk of severe anemia and mortality associated with endemic Plasmodium species in southern Papua, Indonesia. Please see later in the article for the Editors' Summary
Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer (JCOG0212): results from a multicentre, randomised controlled, non-inferiority trial
Authors: Shin Fujita, Takayuki Akasu, Junki Mizusawa, Norio Saito, Yusuke Kinugasa, Yukihide Kanemitsu, Masayuki Ohue, Shoichi Fujii, Manabu Shiozawa, Takashi Yamaguchi, Yoshihiro Moriya
Journal: The Lancet Oncology (2012)
Prevalence of hepatitis C virus antibody in patients with systemic lupus erythematosus
Authors: Y. KARAKOC, K. DILEK, M. GULLULU, M. YAVUZ, A. ERSOY, H. AKALYN, M. YURTKURAN
Journal: Annals of the Rheumatic Diseases (1997)

Systemic lupus erythematosus (SLE) is a disease of unknown aetiology characterised by impaired immune regulation and production of polyclonal autoantibodies. It is reported in the medical literature that in patients with chronic hepatitis resulting from hepatitis C virus (HCV) more autoantibodies such as antinuclear antibodies, anti-ds DNA, antiphospholipid antibody, antithyroglobulin antibody, rheumatoid factor, cryoglobulinaemia, and anti-GOR (an HCV induced, host derived epitope) are seen than in patients with other causes of hepatitis virus.1-3 There have also been reports on HCV associated with several immunological …
Factitious Diabetes Mellitus and Spontaneous Hypoglycemia: Consequences of unrecognized Munchausen syndrome by proxy
Authors: Christopher S Kovacs, Ellen L Toth
Journal: Diabetes Care (1993)

To increase health-care professionals' awareness and knowledge of factitious illness by proxy, or Munchausen syndrome by proxy, in relatives of diabetic patients.A case report is described of a 14-yr-old male who has a 6-yr history of diet-controlled diabetes mellitus, and a 6-mo history of reported spontaneous hypoglycemia.Neither diabetes nor spontaneous hypoglycemia was present in this child on objective testing. The child was subjected to inappropriate use of a strict diabetic diet and daily glucometer measurements for at least 8 yr. The father had convinced his son and health-care professionals of these diagnoses, in spite of evidence of the contrary.When confronted with history and clinical findings that contradict laboratory findings, health-care professionals should have a high index of suspicion for factitious illness and should pursue it aggressively with the help of legal services.
Open-Label, Multicenter, Randomized Phase III Trial of Adjuvant Chemoradiation Plus Interferon Alfa-2b Versus Fluorouracil and Folinic Acid for Patients With Resected Pancreatic Adenocarcinoma
Authors: Jan Schmidt, Ulrich Abel, Jürgen Debus, Sabine Harig, Katrin Hoffmann, Thomas Herrmann, Detlef Bartsch, Justus Klein, Ulrich Mansmann, Dirk Jäger, Lorenzo Capussotti, Reiner Kunz, Markus W. Büchler
Journal: Journal of Clinical Oncology (2012)

Adjuvant chemotherapy prolongs survival in patients with pancreatic cancer, but its benefit is limited. Long-term survival times of up to 44 months after adjuvant chemoradioimmunotherapy in phase II trials motivated the present study.Between 2004 and 2007, 132 R0/R1 resected patients received either fluorouracil (FU), cisplatin, and interferon alfa-2b (IFN α-2b) plus radiotherapy followed by two cycles of FU (arm A, n=64) or six cycles of FU monotherapy (arm B, n=68). One hundred ten patients (arm A, n=53; arm B, n=57) received at least one dose of the study medication, and these patients composed the per-protocol (PP) population. Biomarkers were analyzed longitudinally for their predictive value.Median survival for all randomly assigned patients was 26.5 months (95% CI, 21.6 to 39.5 months) in arm A and 28.5 months (95% CI, 20.4 to 38.6 months) in arm B. The hazard ratio was 1.04 (arm A v arm B: 95% CI, 0.66 to 1.53; P=.99). Median survival for the PP population was 32.1 months (95% CI, 22.8 to 42.2 months) in arm A and 28.5 months (95% CI, 19.5 to 38.6 months) in arm B (P=.49). Eighty-five percent of patients in arm A and 16% of patients in arm B experienced grade 3 or 4 toxicity. The quality of life was temporarily negatively affected in arm A.The FU, cisplatin, and IFN α-2b plus radiotherapy regimen did not improve the survival compared with FU monotherapy. Given the substantial adverse effects, this treatment can currently not be recommended. Nevertheless, the outcome in both arms represents the best survival, to our knowledge, ever reported for patients with resected pancreatic cancer in randomized controlled trials. Future studies will demonstrate whether immune response to IFN α-2b challenge has a predictive value.
A meta-analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease
Authors: Paul Klimo, Clinton J. Thompson, John R.W. Kestle, Meic H. Schmidt
Journal: Neuro-Oncology (2005)

Radiotherapy has been the primary therapy for managing metastatic spinal disease; however, surgery that decompresses the spinal cord circumferentially, followed by reconstruction and immediate stabilization, has also proven effective. We provide a quantitative comparison between the "new" surgery and radiotherapy, based on articles that report on ambulatory status before and after treatment, age, sex, primary neoplasm pathology, and spinal disease distribution. Ambulation was categorized as "success" or" rescue" (proportion of patients ambulatory after treatment and proportion regaining ambulatory function, respectively). Secondary outcomes were also analyzed. We calculated cumulative success and rescue rates for our ambulatory measurements and quantified heterogeneity using a mixed-effects model. We investigated the source of the heterogeneity in both a univariate and multivariate manner with a meta-regression model. Our analysis included data from 24 surgical articles (999 patients) and 4 radiation articles (543 patients), mostly uncontrolled cohort studies (Class III). Surgical patients were 1.3 times more likely to be ambulatory after treatment and twice as likely to regain ambulatory function. Overall ambulatory success rates for surgery and radiation were 85% and 64%, respectively. Primary pathology was the principal factor determining survival. We present the first known formal meta-analysis using data from nonrandomized clinical studies. Although we attempted to control for imbalances between the surgical and radiation groups, significant heterogeneity undoubtedly still exists. Nonetheless, we believe the differences in the outcomes indicate a true difference resulting from treatment. We conclude that surgery should usually be the primary treatment with radiation given as adjuvant therapy. Neurologic status, overall health, extent of disease (spinal and extraspinal), and primary pathology all impact proper treatment selection.
Lipid-Metabolizing CYPs in the Regulation and Dysregulation of Metabolism
Authors: David Bishop-Bailey, Scott Thomson, Ara Askari, Ashton Faulkner, Caroline Wheeler-Jones
Journal: Annual Review of Nutrition (2014)

The cytochrome P450s (CYPs) represent a highly divergent class of enzymes involved in the oxidation of organic compounds. A subgroup of CYPs metabolize ω3-arachidonic and linoleic acids and ω6-docosahexaenoic and eicosapentaenoic polyunsaturated fatty acids (PUFAs) into a series of related biologically active mediators. Over the past 20 years, increasing evidence has emerged for a role of these PUFA-derived mediators in physiological and pathophysiological processes in the vasculature, during inflammation, and in the regulation of metabolism. With recent technological advances and increased availability of lipid mass spectroscopy, we are now starting to discern the patterns of these CYP-PUFA products in health and disease. These analyses not only are revealing the diverse spectrum of lipid nutrients regulated by CYPs, but also clearly indicate that the balance of these mediators changes with dietary intake of different PUFA classes. These findings suggest that we are only just beginning to understand all of the relevant lipid species produced by CYP pathways. Moreover, we are still a long way from understanding the nature and presence of their receptors, their tissue expression, and the pathophysiological processes they regulate. This review highlights these future issues in the context of lipid-metabolizing CYP enzymes, focusing particularly on the CYP450 family of epoxygenases and the lipid mediators they produce.
Associations Between Structural Capabilities of Primary Care Practices and Performance on Selected Quality Measures
Authors: Mark W. Friedberg, Kathryn L. Coltin, Dana Gelb Safran, Marguerite Dresser, Alan M. Zaslavsky, Eric C. Schneider
Journal: Annals of Internal Medicine (2009)

Background: Recent proposals to reform primary care have encouraged physician practices to adopt such structural capabilities as performance feedback and electronic health records. Whether practices with these capabilities have higher performance on measures of primary care quality is unknown. Objective: To measure associations between structural capabilities of primary care practices and performance on commonly used quality measures. Design: Cross-sectional analysis. Setting: Massachusetts. Participants: 412 primary care practices. Measurements: During 2007, 1 physician from each participating primary care practice (median size, 4 physicians) was surveyed about structural capabilities of the practice (responses representing 308 practices were obtained). Data on practice structural capabilities were linked to multipayer performance data on 13 Healthcare Effectiveness Data and Information Set (HEDIS) process measures in 4 clinical areas: screening, diabetes, depression, and overuse. Results: Frequently used multifunctional electronic health records were associated with higher performance on 5 HEDIS measures (3 in screening and 2 in diabetes), with statistically significant differences in performance ranging from 3.1 to 7.6 percentage points. Frequent meetings to discuss quality were associated with higher performance on 3 measures of diabetes care (differences ranging from 2.3 to 3.1 percentage points). Physician awareness of patient experience ratings was associated with higher performance on screening for breast cancer and cervical cancer (1.9 and 2.2 percentage points, respectively). No other structural capabilities were associated with performance on more than 1 measure. No capabilities were associated with performance on depression care or overuse. Limitation: Structural capabilities of primary care practices were assessed by physician survey. Conclusion: Among the investigated structural capabilities of primary care practices, electronic health records were associated with higher performance across multiple HEDIS measures. Overall, the modest magnitude and limited number of associations between structural capabilities and clinical performance suggest the importance of continuing to measure the processes and outcomes of care for patients. Primary Funding Source: The Commonwealth Fund.
Is There a New Drug Beyond Floxuridine for Intra-Arterial Hepatic Chemotherapy in Liver Metastases From Colorectal Cancer?
Authors: G. Fiorentini, S. Rossi, P. Bernardeschi, M. Cantore, S. Guadagni
Journal: Journal of Clinical Oncology (2005)

week,andFUDRat0.12mg/kgpumpvolumepumpflow rate in an adjuvant regimen is feasible. With a median follow-up time of 26 months, the 2-year survival rate is 89%. All 27 patients who were treated at MTD are alive. The choice of irinotecan for systemic therapy was used because lung metastases express a higher level of thymydylate synthetase (TS) than in other sites, 2 and fluorouracil or FUDR (inhibitors of TS)maynotbethemostappropriatedrugtousetocontrolthe development of disease in the lung. Instead, these drugs are active in liver metastases in which TS could be lower. This hypothesis is not totally accepted. More reports show that in