tbuckley/cabot-search huggingface dataset:
The R-1 Factor, a Histocompatibility Antigen in the Rat
Authors: Arthur E. Bogden, Paul M. Aptekman
Journal: Cancer Research (1960)

Summary  Studies of the humoral antibody response in rats of the random-bred Wistar strain, resistant to implantation of its “native” ascites tumor (AA), revealed a hemagglutinin that reacted with the erythrocytes of 90 per cent of Wistar strain rats.  The presence or absence of this hemagglutinogen (termed R-1 factor hemagglutinogen) in the host9s tissues determined intraperitoneal AA tumor growth or rejection, respectively.  A second (weaker ?) histocompatibility factor was detected by subcutaneous implantation of AA ascites and appeared to be nonhemagglutinogenic.  Based upon a multiple allele hypothesis this study has indicated the existence of three alleles controlling the presence or absence of two possible histocompatibility antigens,  R-1 a   (BC),  R-1 b   (Bc), and  R-1 c   (bc). The hemagglutinogen has been designated as B.  Several rat strains were screened for the R-1 hemagglutinogen (B). The inbred P.A. strain was 100 per cent R-1-positive, and the inbred Lewis strain was 100 per cent R-1-negative, indicating the homogeneity of inbred systems. Heterogeneity was indicated in the random-bred Wistar strain (90 per cent R-1 positive), and in the pen-bred Chocolate strain (88 per cent R-1-positive).  The anti-R-1 (anti-B) hemagglutinin appeared to be a “serum agglutinin” resembling the incomplete form of the human Rh antibody in that its avidity for the R-1-positive erythrocyte was markedly reduced in saline concentrations greater than that found normally in serum.  A cytotoxic antibody reactive against the  R-1 a   AA tumor could be induced in  R-1 c   rats by both normal and tumor tissues containing the R-1 hemagglutinogen.  The cytotoxic antibody in anti-R-1 sera was easily and completely absorbable by R-1-positive tumor cells but only partially by R-1-positive erythrocytes.  The parallelism between the activity of the R-1 antigens in the rat and the H-2 antigens in the mouse, and the relationship of the R-1 factor to certain blood groups in the rat, are discussed.
Disease course and late sequelae of Langerhans' cell histiocytosis: 25-year experience at the University of California, San Francisco.
Authors: B Willis, A Ablin, V Weinberg, S Zoger, W M Wara, K K Matthay
Journal: Journal of Clinical Oncology (1996)

PURPOSE The purpose of our investigation was to correlate the extent and degree of organ involvement at presentation of Langerhans' cell histiocytosis (LCH) with subsequent disease course, survival, and late sequelae. MATERIALS AND METHODS The medical records of 71 patients with a pathologic diagnosis of LCH, age 0 to 21 years, who presented between January 1, 1969 and June 30, 1994, were reviewed for organ involvement at diagnosis, treatment, disease course, and late sequelae. Supplementary data were obtained by mailed questionnaire. RESULTS The median follow-up time from diagnosis for all patients was 8.1 years. Involvement at diagnosis included nine patients with skin-only disease, 22 with monostotic disease, 12 with polyostotic disease, and 28 with multisystem presentation. Treatment was surgery only in 17 and chemotherapy and/or radiotherapy in 54 patients. Recurrences were seen in 35 patients, with the highest rate in the polyostotic group. Ten patients died: seven with the multisystem presentation, two with monostotic disease, and one with skin-only disease. Causes included progressive LCH (n = 6) and late sequelae of either treatment (n = 3) or disease (n = 1). Late sequelae were seen in 64% of 51 patients with more than 3 years of follow-up data. The most common were skeletal defects in 42%, dental problems in 30%, diabetes insipidus in 25%, growth failure in 20%, sex hormone deficiency in 16%, hypothyroidism in 14%, hearing loss in 16%, and other CNS dysfunction in 14%. The overall estimated survival rates at 5, 15, and 20 years are 88%, 88%, and 77%, with an estimated event-free survival rate of only 30% at 15 years. CONCLUSION Despite the favorable survival, more than half of LCH patients will have further dissemination of disease or late sequelae, including even some patients with single-system disease at diagnosis. Future treatment needs to be designed to prevent disease progression and late sequelae.
Increased mortality after successful treatment for Hodgkin's disease.
Authors: M M Hudson, C A Poquette, J Lee, C A Greenwald, A Shah, X Luo, E I Thompson, J A Wilimas, L E Kun, W M Crist
Journal: Journal of Clinical Oncology (1998)

PURPOSE To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.
Late-breaking abstract: Effects of a dual CysLT1/2 antagonist, ONO-6950, on allergen-induced airway responses in subjects with mild allergic asthma
Authors: Gail Gauvreau, Louis-Philippe Boulet, J. Mark FitzGerald, Donald Cockcroft, Beth Davis, Richard Leigh, Masaya Tanaka, John Fourre, Makoto Tanaka, Toshiya Nabata, Paul O'Byrne
Journal: European Respiratory Journal (2014)

Background: The cysteinyl leukotrienes (CysLTs) play a key role in the pathophysiology of asthma. In addition to functioning as potent bronchoconstrictors, CysLTs contribute to airway inflammation through eosinophil and neutrophil chemotaxis, plasma exudation and mucus secretion.  Aim: To test the activity of the dual CysLT1/2 antagonist, ONO-6950, against allergen-induced airway responses.  Methods: Subjects with documented allergen-induced early (EAR) and late (LAR) asthmatic responses were randomized in a 3-way crossover study to receive ONO -6950 (200 mg) or montelukast (10 mg) or placebo q.d. on Days 1-8 of the 3 treatment periods. Allergen was inhaled on Day 7 and forced expiratory volume in 1 second (FEV 1 ) was measured for 7 hours following challenge. Sputum eosinophils, and airway hyperresponsiveness were measured before and after allergen challenge. The primary outcome was the effect of ONO-6950 versus placebo on the EAR and LAR.  Results: Twenty-five non-smoking subjects with mild allergic asthma were enrolled and 20 subjects completed all 3 treatment periods per protocol. ONO-6950 was well tolerated. Compared to placebo, ONO-6950 significantly attenuated the maximum % fall in FEV 1  and area under the %FEV 1 /time curve during the early and late asthmatic responses (p  Conclusions: Attenuation of EAR, LAR, and airway inflammation is consistent with CysLT1 blockade. Whether dual CysLT1/2 antagonism offers additional benefit for treatment of asthma requires further study.  Funded by ONO Pharmaceutical Co., Ltd., and AllerGen NCE Inc.
Hearing Loss in Chronic Renal Failure-Hearing Threshold Changes following Haemodialysis
Authors: D Gatland, B Tucker, S Chalstrey, M Keene, L Baker
Journal: Journal of the Royal Society of Medicine (1991)

The prevalence of sensorineural hearing loss, measured by pure tone audiometry, was determined in 66 patients with chronic renal failure and threshold changes following haemodialysis were measured in 31 patients. The incidence of hearing loss was 41% in the low, 15% in the middle and 53% in the high frequency ranges respectively. No correlations with weight changes, haematocrit, metabolic bone disease or ototoxic drug history were found. Of 62 ears studied, 38% had a decrease in low frequency threshold after dialysis and 9% had an increase. Threshold in 22/31 ears with pre-existing low frequency loss altered after dialysis with little change in other frequencies and no correlation with weight changes. In conclusion, we find a high incidence of low and high frequency hearing losses in chronic renal failure patients. Fluctuation in low frequencies with dialysis is common. Possible mechanisms include treatment induced changes in fluid and electrolyte composition of endolymph.
Peroxisome Proliferator–Activated Receptor γ Coactivator 1α and FoxO3A Mediate Chondroprotection by AMP‐Activated Protein Kinase
Authors: Xianling Zhao, Freyr Petursson, Benoit Viollet, Martin Lotz, Robert Terkeltaub, Ru Liu‐Bryan
Journal: Arthritis & Rheumatology (2014)

Objective AMP‐activated protein kinase (AMPK) inhibits chondrocyte procatabolic responses to inflammation and biomechanical injury. This study was undertaken to test the hypothesis that peroxisome proliferator–activated receptor γ coactivator 1α (PGC‐1α) and FoxO3A, 2 major AMPK downstream targets, mediate the chondroprotective effect of AMPK activation. Methods We assessed the activity of AMPKα (threonine 172 phosphorylation) and the expression of PGC‐1α and FoxO3A in human chondrocytes and AMPKα1‐ or AMPKα2‐knockout mouse chondrocytes by Western blotting, and in mouse knee cartilage by immunohistochemistry. We also knocked down or overexpressed PGC‐1α and FoxO3A by small interfering RNA or plasmid DNA transfection, respectively. We assessed mitochondrial superoxide generation using MitoSOX Red. Results Expression of PGC‐1α and FoxO3A was enhanced by pharmacologic AMPK activator A‐769662 but impaired in AMPKα1 −/− or AMPKα2 −/− mouse chondrocytes. Reduced expression of PGC‐1α and FoxO3A was observed in mouse knee instability–induced osteoarthritis (OA) cartilage and in aged C57BL/6 mouse knee cartilage. Knockdown of PGC‐1α and FoxO3A enhanced, but limited the ability of A‐769662 to inhibit, phosphorylation of p65 NF‐κB (Ser 536 ) and procatabolic responses induced by inflammatory cytokines. Forced expression of PGC‐1α and FoxO3A induced increased expression of superoxide dismutase 2 (SOD2) and catalase, but A‐769662 failed to increase the expression of SOD2 and catalase in either PGC‐1α– or FoxO3A‐knockdown chondrocytes. Last, menadione‐induced superoxide generation was inhibited by AMPK pharmacologic activators and by overexpression of PGC‐1α or FoxO3A. Conclusion PGC‐1α and FoxO3A limit oxidative stress and at least partially mediate the capacity of AMPK activity to block procatabolic responses in chondrocytes, and therefore have the potential to inhibit the progression of cartilage damage in OA.
The relationship between peak exercise capacity and pulmonary function in patienst with metabolic syndrome
Authors: Cemile Bozdemir Ozel, Hulya Arikan, Raziye Nesrin Demirtas, Melda Saglam, Naciye Vardar-Yagli, Ebru Calik-Kutukcu, Ozgen Celer, Aysen Akalin, Fusun Alatas
Journal: European Respiratory Journal (2014)

Introduction:  The measurements of exercise capacity are important and widely used in cardiopulmonary diseases. Exercise capacity (EC) can be measured by walking tests which provide a valid and easily accessible method correlated to maximal oxygen consumption. The incremental shuttle walking test (ISWT) is an field test used to measure peak EC with similar accuracy as when estimated from peak oxygen uptake.   Aim:  The aim of this study was to investigate correlation between peak EC and pulmonary function in metabolic syndrome (MS).   Methods:  A total of 29 participants (mean age 44.03±9.7 years) comprised of 11 male and 18 female with MS were eligible to participate in the study. It was determinedpeak EC by incremental shuttle walking test (ISWT) and submaximal EC with 6 minute walk test (6MWT). The pulmonary function and maximal inspiratory and expiratory muscle strength (MIP, MEP) were assessed with spirometer and cabin body-plethysmography.   Results:  The distance walked on ISWT was 528.27±115.7m that was correlated with 6MWT (r=0.702 p=0.001). In addition, there were significant associations between distance walked on ISWT and MIP (r=0.494, p=0.006), MEP (r=0.429, p=0.020), TLC (r=0.456, p=0.013), VC (r=0.625, p=0.000), IC (r=0.430, p=0.020), FVC (r=0.692, p=0.000), FEV 1  (r=0.730, p=0.000), MEF 75  (r=0.584, p=0.000), MEF 50  (r=0.570, p=0.001), MEF %25-75  (r=0.490, p=0.007).   Conclusions:  Our results suggested that different parameters of lung function were closely correlated with peak exercise capacity. Therefore, lung function could be also estimated with peak EC from distance walked on ISWTlike 6MWT commonly used, which is a practical, simple, inexpensive test in subjects with MS.
In Vivo Synchrony of Solid B16 Melanoma by Cytosine Arabinoside, an Inhibitor of DNA Synthesis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Gibson Mh, Bertalanffy Fd
Journal: JNCI Journal of the National Cancer Institute (1972)

1-β-Arabinofuranosylcytosine (ara-C), an inhibitor of DNA synthesis, was used to produce a high degree of in vivo cell synchrony in B16 melanoma, a solid transplantable mouse tumor. The degree of synchrony achieved depended on the dosage of the drug, the interval between successive injections, and the total duration of ara-C action. The mitotic index of the tumor cell population likewise reflected a degree of cell synchrony. The extent of cell kill produced by ara-C was a further decisive factor in the degree of synchrony achieved.—J Natl Cancer Inst 49: 1007–1018, 1972.
Effect of Corynebacterium parvum on Tumor Growth in Normal and Athymic (Nude) Mice 2 3
Authors: Michael F. A. Woodruff, Noel L. Warners
Journal: JNCI Journal of the National Cancer Institute (1977)

The effect of systemic or local injection of Corynebacterium parvum at the tumor site on the growth of various murine tumors was studied in intact and congenitally athymic BALB/c mice. Systemic injection of C. parvum usually had a marked antitumor effect in both types of mouse. Two lymphomas, which regressed spontaneously in untreated intact mice but not in athymlc mice, grew progressively in intact mice given systemic C. parvum, though their growth was inhibited in similarly treated athymic mice. Local injection into the site of the tumor markedly inhibited tumor growth in intact mice but was without effect in athymic mice. C. parvum was believed to exert its antitumor effects by two different mechanisms, only one of which was T-cell dependent. The mechanism not dependent on T-cells was particularly activated by systemic C. parvum injection.
Elafin in Pulmonary Arterial Hypertension. Beyond Targeting Elastases
Authors: Hyung J. Chun, Paul B. Yu
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

that macrolide use (generally in a combination regimen) was associated with an 18% reduction in mortality compared with in nonmacrolide regimens and that a b-lactam/macrolide combination had a trend to reduced mortality compared with a b-lactam/quinolone regimen (8).In another study of patients with CAP with sepsis, the use of a macrolide was associated with a lower mortality than when a macrolide was not used, and the benefit applied even if macrolide resistance was present, implying the benefit was not related to an antimicrobial effect (9).In nonsevere CAP, the benefit of adjunctive macrolide therapy is less clear, with one recent randomized trial suggesting a benefit and another showing no benefit (10, 11).All of these data, along with the findings of Cilloniz and colleagues, suggest that even if macrolide-resistant pneumococci are common in CAP, they do not affect the severity of illness on presentation, and they should be considered for routine use, generally as part of a combination regimen, especially for those with severe CAP and sepsis, because of their nonantibiotic effects.Although pneumococcal resistance to macrolides has partially diminished their antimicrobial efficacy, these agents have beneficial pleiotropic effects on patients with CAP, and consequently should still be viewed as an essential part of our therapeutic armamentarium.
Complementary and alternative medicine use among pediatric oncology patients in a tertiary care center, Riyadh, Saudi Arabia.
Authors: R. Al Sudairy, A. Al Omari, M. Jarrar, T. Al Harbi, K. Al Jamaan, H. Tamim, A. R. Jazieh
Journal: Journal of Clinical Oncology (2011)

e20003 Background: Complementary and alternative medicine (CAM) use among children with cancer is well established in the literatures world-wide. However, no data is available on the use of CAM among pediatric oncology patients in Saudi Arabia. This study aims at determining the prevalence and pattern of CAM use in this population. Methods: This is a cross-sectional descriptive study which included pediatric cancer patients (up to age 14 years) who are treated at King Abdulaziz Medical City in Riyadh, Saudi Arabia. An interview-administered questionnaire was used. Demographic data, disease profile, details of CAM use and informing the treating physician about CAM use were obtained. Results: Of the 41 participating patients, 30 were males (73.2%) and 11 were females (26.8%). 40 patients were Saudi (97.6%). Median age at diagnosis was 4.4 years (0.1-13.4). There were 28 patients with acute lymphoblastic leukemia (66.7%), lymphoma 7 patients (16.7%), and solid tumors 7 patients (16.7%). Parents of 25 patients (61%) thought that the cause of the disease was “envy” by others. All patients used non-dietary CAM like Quran Recitation and Rugya and 36 patients (87.8%) used Duaa (supplication). Dietary supplements (DS) were used by 39 patients (95%) including honey in 30 patients (73%), Black Seed in 25 patients (61%), olive oil (external use) in 28 patients (68%), Zamzam water in 31 patients (76%), water with Quran recited on it in 20 patients (48.8%), and different herbal mixtures in 12 patients (29%). All parents believed that CAM helps in cure. Comfort and piece from CAM use were perceived by 33 patients (80.5%), increase activity in 12 patients (29%), decrease pain intensity in 9 patients (22%) and increase immunity in 8 patients (19.5%). Physicians were informed about CAM use by 26 patients (63.4%) and parents decided to delay medical treatment while using CAM in 3 patients (7.3%). Conclusions: Our study revealed that CAM is widely used among pediatric oncology patients following their spiritual beliefs as well as traditional dietary habits highlighting the need for physicians’ awareness and counseling when appropriate.
Selection without multiple replicators?
Authors: John W. Pepper, Thorbjørn Knudsen
Journal: Behavioral and Brain Sciences (2001)

Hull et al.'s construction of operant learning as an instance of selection gives rise to problems that weaken this application of selection theory beyond acceptable limits. We point out that most fundamental is a disregard for the need to include multiple concurrent replicators in any definition of selection and indicate how this problem may be solved.
Management of cystic fibrosis patients - The South Australian lung transplant satellite centre experience
Authors: Vinod Aiyappan, Hugh Greville, Mary Kelly, Rosie Player, Mark Holmes, Chien-Li Holmes-Liew
Journal: European Respiratory Journal (2012)

Introduction: Lung Transplantation (LTx) has been shown to improve the morbidity and mortality in selected patients with cystic fibrosis (CF). The South Australian (SA) LTx unit is a unique non-surgical LTx centre, which manages CF patients pre and post-operatively (after 3 months of transplant).There is to date no published data regarding the outcomes of LTx recipients with CF who are being managed by a satellite centre.  Aim: To measure the outcomes of CF patients managed by the SA lung transplant unit and compare this with national and international data  Methods: Retrospective single-centre observational study using case-notes and laboratory data  Results: Thirty one SA CF patients received LTx between 1990-2011.This accounts for 25.4% of LTx recipients managed at this centre (Compared to 26.9% from 2010 International society for heart and lung transplantation (ISHLT) data and 35% from the Australia and New Zealand Cardiothoracic Organ Transplant Registry(ANZCOTR). Mean age at LTx transplant was 29 years. Twenty-eight patients received double lung transplant and 3 patients received heart-lung transplant. Mean FEV1 pre-LTx was 19.6% predicted. 1-year survival post LTx was 94% and 5-year-survival after LTx was 66.7% compared to 84.3% and 60.58% (ISHLT data) and 87.8% and 60% (ANZCOTR data) respectively. Sixty four percent of patients were free from bronchiolitis obliterans syndrome (BOS) at the end of 5 years, compared to 53.9% (ISHLT).  Conclusions: Outcomes from management at the SA satellite centre following LTx for CF are equivalent or better than Australian and International results.
CBT for Adolescents With Anxiety: Mature Yet Still Developing
Authors: Philip C. Kendall, Jeremy S. Peterman
Journal: American Journal of Psychiatry (2015)

Anxiety disorders are common in adolescents (ages 12 to 18) and contribute to a range of impairments. There has been speculation that adolescents with anxiety are at risk for being treatment nonresponders. In this review, the authors examine the efficacy of cognitive-behavioral therapy (CBT) for adolescents with anxiety. Outcomes from mixed child and adolescent samples and from adolescent-only samples indicate that approximately two-thirds of youths respond favorably to CBT. CBT produces moderate to large effects and shows superiority over control/comparison conditions. The literature does not support differential outcomes by age: adolescents do not consistently manifest poorer outcomes relative to children. Although extinction paradigms find prolonged fear extinction in adolescent samples, basic research does not fully align with the processes and goals of real-life exposure. Furthermore, CBT is flexible and allows for tailored application in adolescents, and it may be delivered in alternative formats (i.e., brief, computer/Internet, school-based, and transdiagnostic CBT).