tbuckley/cabot-search huggingface dataset:
Response to Treatment with the Leukocyte-derived Immunomodulator IMREG-1 in Immunocompromised Patients with AIDS-related Complex
Authors: M S Gottlieb, R A Zackin, M Fiala, D H Henry, A J Marcel, K L Combs, J Vieira, H A Liebman, L A Cone, K S Hillman
Journal: Annals of Internal Medicine (1991)

▪ Objective: To determine if a 6-month course of therapy with IMREG-1, a leukocyte-derived immunomodulator, slows disease progression in patients with AIDS-related complex. ▪ Design: Randomized, double-blind trial. ▪ Setting: Five academic- and three community-based clinics. ▪ Patients: Immunocompromised patients (143) with HIV. ▪ Interventions: IMREG-1 or placebo every 2 weeks (13 doses). ▪ Main Results: Twelve of forty-eight patients on placebo and 5 of 95 patients on IMREG-1 experienced adverse events (AIDS-defining opportunistic infection or neoplasm, wasting syndrome, HIV-associated encephalopathy, or peripheral sensory neuropathy). Based on an intention-to-treat analysis, Kaplan-Meier event probabilities were 26% for the placebo group and 6% for the IMREG-1 group (P < 0.001); based on the Cox proportional hazards model, the relative risk for patients on placebo compared with patients on IMREG-1 was 5.1 (95% Cl, 1.8 to 14.8). The frequency of symptoms significantly increased from baseline in patients receiving placebo. The mean decrease in CD4+ cells from baseline was 80 X 106 cells/L in the placebo group and 29 X 106 cells/L in patients on IMREG-1, with 20% (8) and 38% (32) of patients, respectively, showing a trend toward an increase (P = 0.04). In patients receiving IMREG-1, the size and rate of delayed hypersensitivity responses were larger than in the placebo group. ▪ Conclusions: Patients with AIDS-related complex experienced fewer adverse events and constitutional symptoms after IMREG-1 treatment. The slower loss of CD4+ cells and increased size and rate of delayed hypersensitivity responses most likely reflect the effect of IMREG-1 on the immune system. No toxicity related to IMREG-1 administration was observed.
Fibronectin mRNA and protein accumulation, distribution, and breakdown in rabbit anti-glomerular basement membrane disease.
Authors: M Goyal, R Wiggins
Journal: Journal of the American Society of Nephrology (1991)

Fibronectin is a multifunctional matrix protein which by immunofluorescence appears to be present in increased amounts during glomerular injury. To examine fibronectin metabolism in glomerular injury, an anti-glomerular basement membrane model that progresses to severe glomerular crescent formation, glomerulosclerosis, and interstitial fibrosis was used. Fibronectin was purified from rabbit plasma, and a monoclonal antibody raised against rabbit fibronectin was used for immunolocalization and quantitation of fibronectin protein. RNA and protein were extracted from isolated glomeruli and whole renal cortex at various times during progression of disease. At day 4, there was a 2.5-fold increase in fibronectin protein which by immunofluorescence appeared to be in the glomerular mesangial area. There was no increase in glomerular fibronectin mRNA at this time. This discrepancy is consistent with the conclusion that, at this early time point, the increased glomerular fibronectin comes predominantly from plasma. By day 7, glomerular fibronectin mRNA and extractable fibronectin protein were increased in association with bright immunofluorescence along the inner aspect of Bowman's capsule where early crescents were forming. Similarly, at day 14, crescents stained very brightly for fibronectin. These results are consistent with the conclusion that, at later time points, fibronectin is synthesized in glomeruli in association with cell division and crescent formation. Degradation of fibronectin in glomerular and cortical extracts was demonstrated under normal and nephritic conditions by finding fibronectin proteolytic fragmentation by Western blot.(ABSTRACT TRUNCATED AT 250 WORDS)
Emerging roles for macrophages in cardiac injury: cytoprotection, repair, and regeneration
Authors: Nikolaos G. Frangogiannis
Journal: Journal of Clinical Investigation (2015)

The mammalian heart contains a population of resident macrophages that expands in response to myocardial infarction through the recruitment of monocytes. Infarct macrophages exhibit high phenotypic diversity and respond to microenvironmental cues by altering their functional properties and secretory profile. In this issue of the JCI, de Couto and colleagues demonstrate that infiltrating macrophages can be primed to acquire a cardioprotective phenotype in ischemic heart and exert this proactive effect through activation of an antiapoptotic program in cardiomyocytes. This study supports the growing body of evidence that suggests that macrophage subpopulations can be modulated to mediate cytoprotective, reparative, and even regenerative functions in the infarcted heart. The cellular mechanisms and molecular signals driving these macrophage phenotypes are yet unknown; however, harnessing the remarkable potential of the macrophage in regulating cell survival and tissue regeneration may hold therapeutic promise for myocardial infarction.
Activation of Natural Killer T Cells Potentiates or Prevents Experimental Autoimmune Encephalomyelitis
Authors: Alex W. Jahng, Igor Maricic, Brian Pedersen, Nicolas Burdin, Olga Naidenko, Mitchell Kronenberg, Yasuhiko Koezuka, Vipin Kumar
Journal: The Journal of Experimental Medicine (2001)

Natural killer (NK) T cells recognize lipid antigens in the context of the major histocompatibility complex (MHC) class 1–like molecule CD1 and rapidly secrete large amounts of the cytokines interferon (IFN)-γ and interleukin (IL)-4 upon T cell receptor (TCR) engagement. We have asked whether NK T cell activation influences adaptive T cell responses to myelin antigens and their ability to cause experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. While simultaneous activation of NK T cells with the glycolipid α-galactosylceramide (α-GalCer) and myelin-reactive T cells potentiates EAE in B10.PL mice, prior activation of NK T cells protects against disease. Exacerbation of EAE is mediated by an enhanced T helper type 1 (Th1) response to myelin basic protein and is lost in mice deficient in IFN-γ. Protection is mediated by immune deviation of the anti-myelin basic protein (MBP) response and is dependent upon the secretion of IL-4. The modulatory effect of α-GalCer requires the CD1d antigen presentation pathway and is dependent upon the nature of the NK T cell response in B10.PL or C57BL/6 mice. Because CD1 molecules are nonpolymorphic and remarkably conserved among different species, modulation of NK T cell activation represents a target for intervention in T cell–mediated autoimmune diseases.
Development of a Lymphocyte Transformation Microassay for Murine Leukemia Virus 2
Authors: Robert M. Donahoe, Robert L. Peters, Richard VanVleck, Robert J. Huebner, Gary J. Kelloff
Journal: JNCI Journal of the National Cancer Institute (1976)

A lymphocyte transformation microassay (LTA) was developed from spleen harvests of 6- to 8-week-old BABL/cCr mice. The optimal culture conditions for the microassay were established by measurement of lymphoblastogenesis in response to phytohemagglutin (PHA) and pokeweed mitogen. Immunization, as measured by the LTA, of adult BALB/cCr mice with formalin-inactivated, sucrose-banded, murine type-C viruses was achieved with a three-dose regimen of 200, 100, and 100 μg during 3 successive weeks (Freund's complete adjuvant was used with the first dose). The ip route of immunization induced the best responses in lymphocytes harvested 18 days after the last immunogen was given. The LTA was consistently reproducible, limited only by biological variability of the mouse and the standardization of the antigen preparation. In mice immunized with Rauscher murine leukemia virus (R-MuLV) or AKR MuLV vaccine, the LTA was specific for the C-type virus and could be used to distinguish viral subtypes, because R-MuLV elicited responses significantly different from a B-tropic BALB/c leukemia virus. This specificity was evident when the stimulating antigen was presented as UV-inactivated, sucrose-banded virus or as freeze-thaw extracts of cells infected with MuLV.
Lymphatic Vessels Are Essential for the Removal of Cholesterol from Peripheral Tissues by SR-BI-Mediated Transport of HDL
Authors: Hwee Ying Lim, Chung Hwee Thiam, Kim Pin Yeo, Radjesh Bisoendial, Chung Shii Hii, Kristine C.Y. McGrath, Kar Wai Tan, Alison Heather, J. Steven Jonathan Alexander, Veronique Angeli
Journal: Cell Metabolism (2013)
Bone Marrow Mesenchymal Stem and Progenitor Cells Induce Monocyte Emigration in Response to Circulating Toll-like Receptor Ligands
Authors: Chao Shi, Ting Jia, Simon Mendez-Ferrer, Tobias M. Hohl, Natalya V. Serbina, Lauren Lipuma, Ingrid Leiner, Ming O. Li, Paul S. Frenette, Eric G. Pamer
Journal: Immunity (2011)
Association between antioxidant vitamins and asthma outcome measures: systematic review and meta-analysis
Authors: S Allen, J R Britton, J A Leonardi-Bee
Journal: Thorax (2009)

<h3>Background:</h3> Epidemiological studies suggest that dietary intake of vitamins A, C and E may be associated with the occurrence of asthma. A systematic review and meta-analysis was conducted in accordance with MOOSE guidelines to determine whether vitamins A, C and E, measured as dietary intakes or serum levels, are associated with asthma. <h3>Methods:</h3> MEDLINE, EMBASE, CINAHL, CAB abstracts and AMED (up to November 2007), conference proceedings and bibliographies of papers were searched to identify studies of asthma, wheeze or airway responsiveness in relation to intakes and serum concentrations of vitamins A, C and E. Pooled odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI) were estimated using random effects models. <h3>Results:</h3> A total of 40 studies were included. Dietary vitamin A intake was significantly lower in people with asthma than in those without asthma (MD −182 μg/day, 95% CI −288 to −75; 3 studies) and in people with severe asthma than in those with mild asthma (MD −344 μg/day; 2 studies). Lower quantile dietary intakes (OR 1.12, 95% CI 1.04 to 1.21; 9 studies) and serum levels of vitamin C were also associated with an increased odds of asthma. Vitamin E intake was generally unrelated to asthma status but was significantly lower in severe asthma than in mild asthma (MD −1.20 μg/day, 95% CI −2.3 to −0.1; 2 studies). <h3>Conclusions:</h3> Relatively low dietary intakes of vitamins A and C are associated with statistically significant increased odds of asthma and wheeze. Vitamin E intake does not appear to be related to asthma status.
Respiratory heat and moisture loss is associated with eosinophilic inflammation in asthma
Authors: D. D. Noble, J. B. McCafferty, A. P. Greening, J. A. Innes
Journal: European Respiratory Journal (2006)

Increased mucosal vascularity is a hallmark of airway inflammation in asthma. It was hypothesised that this would lead to a detectable increase in respiratory heat and moisture loss (RHML), which would reflect the degree of airway inflammation present. A total of 23 subjects with asthma and 18 healthy controls had RHML measured in a cross-sectional study. The measurements were made using a device that combines temperature and humidity measurement during inspiration and expiration and allows precise control over inspirate conditions and ventilatory pattern. The subjects with asthma underwent parallel measurements of exhaled nitric oxide, sputum eosinophil percentage and exhaled breath condensate pH. Mean+/-SD RHML was elevated in patients with asthma (98.1+/-7.3 J.L(-1)) compared with control subjects (91.9+/-4.5 J.L(-1)). RHML measurement in asthma correlated with sputum eosinophil percentage. This novel correlation between thermal and cellular measurements in asthma suggests that both of these noninvasive indices are sensitive to the degree of underlying chronic airway inflammation.
A Phase I Study of Intravitreal Vascular Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-Related Macular Degeneration
Authors: Quan Dong Nguyen, Syed Mahmood Shah, David J. Browning, Henry Hudson, Peter Sonkin, Seenu M. Hariprasad, Peter Kaiser, Jason S. Slakter, Julia Haller, Diana V. Do
Journal: Ophthalmology (2009)
Overexpression of FLIPL Is an Independent Marker of Poor Prognosis in Colorectal Cancer Patients
Authors: Gustave J. Ullenhag, Abhik Mukherjee, Nicholas F.S. Watson, Ahmad H. Al-Attar, John H. Scholefield, Lindy G. Durrant
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Colorectal cancer is one of the most common cancers. The tumor necrosis factor–related apoptosis inducing ligand (TRAIL) pathway transmits apoptotic signals and anticancer agents that activate this system, which are in clinical development. We sought to determine the prognostic value of the clinically most relevant members of this pathway in colorectal cancer patients. Experimental Design: We used an arrayed panel of colorectal cancer tissue to assess the protein expression of the functional TRAIL receptors (TRAIL-R1 and TRAIL-R2) and both the long and short forms of FLICE inhibitory protein (FLIPL and FLIPS). Disease-free survival was examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by Cox multivariate analysis. Results: The TRAIL receptors and FLIPS were not associated with survival. On univariate analysis, strong FLIPL expression was associated with a significantly higher survival (P = 0.0082). On multivariate analysis using the Cox proportional hazards model, FLIPL phenotype was significantly associated with a poor prognosis in this series (hazard ratio, 2.04; 95% confidence interval, 1.18-3.56; P = 0.011). Conclusions: Overexpression of FLIPL, but not TRAIL-R1 or TRAIL-R2, provides stage-independent prognostic information in colorectal cancer patients. This may indicate a clinically more aggressive phenotype and a subset of patients for whom more extensive adjuvant treatment would be appropriate.
Outcomes of Nonmyeloablative HLA-Haploidentical Blood or Marrow Transplantation With High-Dose Post-Transplantation Cyclophosphamide in Older Adults
Authors: Yvette L. Kasamon, Javier Bolaños-Meade, Gabrielle T. Prince, Hua-Ling Tsai, Shannon R. McCurdy, Jennifer A. Kanakry, Gary L. Rosner, Robert A. Brodsky, Karlo Perica, B. Douglas Smith, Douglas E. Gladstone, Lode J. Swinnen, Margaret M. Showel, William H. Matsui, Carol Ann Huff, Ivan Borrello, Keith W. Pratz, Michael A. McDevitt, Ivana Gojo, Amy E. Dezern, Satish Shanbhag, Mark J. Levis, Leo Luznik, Richard F. Ambinder, Ephraim J. Fuchs, Richard J. Jones
Journal: Journal of Clinical Oncology (2015)

Purpose Recent advances in nonmyeloablative (NMA), related HLA-haploidentical blood or marrow transplantation (haplo-BMT) have expanded the donor pool. This study evaluated the effect of age on NMA haplo-BMT outcomes in patients age 50 to 75 years. Patients and Methods A retrospective analysis was performed of 271 consecutive patients with hematologic malignancies, age 50 to 75 years, who received NMA, T-cell–replete haplo-BMT with high-dose post-transplantation cyclophosphamide. Results The median age was 61 years, with 115 patients (42%) age 50 to 59, 129 (48%) age 60 to 69, and 27 (10%) age 70 to 75 years. Overall, 84% of patients had intermediate- or high-/very high–risk disease. The 6-month probabilities of grade 3 or 4 acute graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) were 3% and 8%, respectively. Patients in their 50s, 60s, and 70s had 6-month NRM probabilities of 8%, 9%, and 7%, respectively (P = .20). With a median follow-up of 4 years, corresponding 3-year progression-free survival probabilities were 39%, 35%, and 33% (P = .65), and corresponding 3-year overall survival probabilities were 48%, 45%, and 44% (P = .66). Three-year progression-free survival probabilities were 40% in acute myeloid leukemia (n = 65), 39% in aggressive non-Hodgkin lymphoma (n = 83), and 37% in indolent or mantle-cell lymphoma (n = 65). Older patient age was associated with a significantly higher risk of grade 2 to 4 acute GVHD but not grade 3 to 4 acute or chronic GVHD. No statistically significant associations were found between older age (relative to age 50 to 59 years or as a continuous variable) and NRM, relapse, or survival. Conclusion NMA haplo-BMT with post-transplantation cyclophosphamide has encouraging safety and survival outcomes in patients age 50 to 75 years. In patients otherwise fit for BMT, the results support consideration of this approach despite advanced age.
Obsessive-compulsive disorder
Authors: I Heyman
Journal: BMJ (2006)

Obsessive-compulsive disorder is one of the more common serious mental illnesses.The shame and secrecy associated with it, as well as lack of recognition of its characteristic symptoms, can lead to delay in diagnosis and treatment.Effective psychological and drug treatments are available for the distressing, time consuming, repetitive thoughts and rituals and the associated functional impairment.This article reviews the presentation and assessment of obsessivecompulsive disorder and discusses the current best treatment options, as well as directions for the future. MethodsWe searched for the term "obsessive compulsive disorder" in electronic databases and referred to published systematic reviews, including the recently published guideline from the National Institute for Health and Clinical Excellence (NICE). Who gets it and why does it matter?Obsessive-compulsive disorder occurs throughout the life span, and children as young as 6 or 7 present with the characteristic impairing symptoms (box 1).At the other end of the age range, patients may present for the first time in old age.Most adults with the disorder report onset in childhood or adolescence.The condition can result in considerable disability; for example, children may drop out of education and adults can become housebound.The World Health Organization rates obsessive-compulsive disorder as one of the top 20 most disabling diseases.If untreated, it generally persists, 1 yet effective, evidence based psychological and drug treatments are available.Recent epidemiological studies report prevalence rates of 0.8% in adults and 0.25% in 5-15 year old children, 2 3 although earlier studies suggested rates as high as 1-3% in adults and 1-2% in children and adolescents. Why do clinicians need to know about it?People of all ages with obsessive-compulsive disorder understand the senseless nature of their repetitive, unwanted behaviours and intrusive, recurrent thoughts.This may lead to shame, reluctance to seek help, and poor recognition by health professionals.People with the disorder have long delays in accessing effective treatments-17 years on average in one study. 4hey frequently present to non-psychiatrists for treatment (table 1), and psychiatric symptoms go undetected.Greater awareness of the condition is needed in a range of non-psychiatric healthcare settings, and clinicians need to be confident about recognising it.
The current status of sports medicine training in United States internal medicine residency programmes
Authors: C L Sweeney, M Davidson, T Melgar, D Patel, D Cucos
Journal: British Journal of Sports Medicine (2003)

To determine the general status of sports medicine training in internal medicine residency programmes in the United States.A cross sectional survey of the programme directors and chief residents of each of the 407 accredited internal medicine programmes listed in the 1999-2000 Graduate Medical Education Directory.The questionnaire was returned by 231 of 404 (57%) programme directors and 233 of 404 (58%) chief residents. A chief and director of the same programme (paired responses) replied from 144 of 404 (36%) programmes surveyed. A formal sports medicine curriculum was reported by 22.1% of programme directors. Programmes with a formal curriculum were 2.9 times more likely to offer any of the sports medicine educational experiences (p<0.0001; Cochran-Mantel-Haenszel). Programmes with block rotations were more likely to include all of the educational experiences surveyed than those without (p<0.002 for each; chi(2) test). A total of 162 programmes included sports medicine as part of other rotations. Most programmes only included sports medicine as part of other rotations: 44.6% (103/231) of all programmes and 63.6% (103/162) of programmes with sports medicine as part of other rotations. Some 29.9% (69/231) of directors reported having an elective, and 3.9% (9/231) reported a required rotation. Almost a quarter (21.7%; 50/231) of directors reported that their residents received no clinical experience in sports medicine.Little attention is given to the subject of sports medicine when internal medicine residency curricula are developed in the United States. Thus only a small percentage of American internal medicine residency programmes provide significant training in sports medicine.
Ankle: avoid another ankle sprain!
Authors: Evert Verhagen
Journal: British Journal of Sports Medicine (2015)

CYP2J2, an arachidonic acid epoxygenase, is recognized for its role in the first-pass metabolism of astemizole and ebastine. To fully assess the role of CYP2J2 in drug metabolism, a selective substrate and potent specific chemical inhibitor are essential. In this study, we report amiodarone 4-hydoxylation as a specific CYP2J2-catalyzed reaction with no CYP3A4, or other drug-metabolizing enzyme, involvement. Amiodarone 4-hydroxylation enabled the determination of liver relative activity factor and intersystem extrapolation factor for CYP2J2. Amiodarone 4-hydroxylation correlated with astemizole O-demethylation but not with CYP2J2 protein content in a sample of human liver microsomes. To identify a specific CYP2J2 inhibitor, 138 drugs were screened using terfenadine and astemizole as probe substrates with recombinant CYP2J2. Forty-two drugs inhibited CYP2J2 activity by ≥50% at 30 μM, but inhibition was substrate-dependent. Of these, danazol was a potent inhibitor of both hydroxylation of terfenadine (IC<sub>50</sub> = 77 nM) and O-demethylation of astemizole (<i>K</i><sub>i</sub> = 20 nM), and inhibition was mostly competitive. Danazol inhibited CYP2C9, CYP2C8, and CYP2D6 with IC<sub>50</sub> values of 1.44, 1.95, and 2.74 μM, respectively. Amiodarone or astemizole were included in a seven-probe cocktail for cytochrome P450 (P450) drug-interaction screening potential, and astemizole demonstrated a better profile because it did not appreciably interact with other P450 probes. Thus, danazol, amiodarone, and astemizole will facilitate the ability to determine the metabolic role of CYP2J2 in hepatic and extrahepatic tissues.