tbuckley/cabot-search huggingface dataset:
Abstract 2935: Modulation of immune checkpoint B7-H1/B7-DC/PD-1 interaction in combination with live attenuated <i>Listeria monocytogenes</i> expressing a tumor associated antigen effectively treats hepatic colorectal cancer metastases
Authors: Kiyoshi Yoshimura, Kelly Olino, Barish Edil, Satoshi Wada, Xiaoyu Pan, Kristen Meckel, Drew Pardoll, Richard Schulick
Journal: Cancer Research (2010)

Abstract Introduction: The successful eradication of tumor deposits by immunotherapy requires the generation of an appropriate primary and memory immune effector immune response as well as the establishment of a tumor micro-environment within that organ to target, traffic and amplify the appropriate immune response. B7-H1 is expressed on dendritic cells (DCs), macrophages, T/B cells and on various cancer cell lines. B7-H1 when bound to its T-cell receptor, programmed death-1 (PD-1) induces a negative regulatory signal inhibiting T cell responses. These are particularly attractive targets of therapy in metastatic colorectal cancer as the cancer and the liver microenvironment express B7H1, while tumor infiltrating CD8+ T cells express PD-1. It appears that cancer is able to exploit the B7H1-PD-1 inhibitory mechanism thus making the blockade of this interaction capable of enhancing our already validated vaccine platform of doubly attenuated Listeria Monocytogenes (LM). Methods and Results: Isolated hepatic metastases were generated in Balb/c mice and treated with intraperitoneal injections of 0.1 x LD50 of LM on postoperative days 3, 6, 9. In addition, intravenous injection of a mouse anti-mouse B7-H1 blocking antibody was given on days 4,7,10 and compared to mice given vaccine alone, antibody alone, and no treatment. We analyzed immune cell populations in the liver with flow cytometry to define the activity, specificity and kinetics. After blockade of B7-H1 we performed survival analysis and in vitro studies for T cell proliferation of activated T cells. Results: Mice treated with LM and B7-H1 showed a 60% survival, LM alone showed 30% survival, while antibody alone and untreated mice did not survive (Figure 1). We first demonstrated B7-H1 expression on colon cancer cell line CT26. We then found CD8+ T cells and conventional dendritic cells (cDC) treated with LM, showed an up-regulation of B7-H1. However, these receptors upregulation were both abgrogated when combined with B7H1 blocking antibody. When B7H1 blocking antibody was used alone, there was a decrease in B7H1 expression but an increased expression on PD-1 on CD8+ T cells. T cell proliferation assay in vitro showed sustained T cell activity with B7-H1 blockade even in the presence of tumor. Conclusion Blockade of B7-H1 is an effective method of overcoming immune evasion and improves the efficacy of LM vaccine in the treatment of metastatic colorectal cancer to the liver. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2935.
Late Results of Percutaneous Mitral Commissurotomy up to 20 Years
Authors: Claire Bouleti, Bernard Iung, Cédric Laouénan, Dominique Himbert, Eric Brochet, David Messika-Zeitoun, Delphine Détaint, Eric Garbarz, Bertrand Cormier, Pierre-Louis Michel, France Mentré, Alec Vahanian
Journal: Circulation (2012)

Background— Long-term follow-up after percutaneous mitral commissurotomy enables predictive factors of late results to be identified. Methods and Results— Late results of percutaneous mitral commissurotomy were assessed in 1024 consecutive patients. Good immediate results, defined as valve area ≥1.5 cm 2 without mitral regurgitation &gt;2/4, were obtained in 912 patients (89%). These 912 patients were randomly split into 2 cohorts comprising 609 and 303 patients that were used to develop and validate, respectively, a scoring system predicting late functional results. The 20-year rate of good functional results (survival without cardiovascular death, mitral surgery, or repeat percutaneous mitral commissurotomy and in New York Heart Association class I or II) was 30.2±2.0%. A multivariable Cox model identified 7 predictive factors of poor late functional results: higher final mean gradient ( P &lt;0.0001), interaction between age and final mitral valve area ( P &lt;0.0001) showing that the impact of valve area decreases with age, interaction between sex and valve calcification ( P &lt;0.0001) showing that the impact of valve anatomy is stronger in men, and interaction between rhythm and New York Heart Association class showing an impact of New York Heart Association class only in patients in atrial fibrillation ( P &lt;0.0001). A 13-point score enabled 3 risk groups to be defined, corresponding to predicted good functional results of 55.1%, 29.1%, and 10.5% at 20 years in the validation cohort. Conclusions— Twenty years after percutaneous mitral commissurotomy in a population of patients with varied characteristics, 30% still had good functional results. Prediction of late functional results is multifactorial and strongly determined by age and the quality of immediate results. A simple validated scoring system is useful for estimating individual patient outcome.
Was the ANITA Rooting of the Angiosperm Phylogeny Affected by Long-Branch Attraction?
Authors: Yin-Long Qiu, Jungho Lee, Barbara A. Whitlock, Fabiana Bernasconi-Quadroni, Olena Dombrovska
Journal: Molecular Biology and Evolution (2001)

Five groups of basal angiosperms, Amborella, Nymphaeales, Illiciales, Trimeniaceae, and Austrobaileya (ANITA), were identified in several recent studies as representing a series of the earliest-diverging lineages of the angiosperm phylogeny. All of these studies except one employed a multigene analysis approach and used gymnosperms as the outgroup to determine the ingroup topology. The high level of divergence between gymnosperms and angiosperms, however, has long been implicated in the difficulty of reconstructing relationships at the base of angiosperm phylogeny using DNA sequences, for fear of long-branch attraction (LBA). In this study, we replaced the gymnosperm sequences from the five-gene matrix (mitochondrial atp1 and matR, plastid atpB and rbcL, and nuclear 18S rDNA) used in our earlier study with four categories of divergent sequences—random sequences with equal base frequencies or equally AT- and GC-rich contents, homopolymers and heteropolymers, misaligned gymnosperm sequences, and aligned lycopod and bryophyte sequences—to evaluate whether the gymnosperms were an appropriate outgroup to angiosperms in our earlier study that identified the ANITA rooting. All 24 analyses performed rooted the angiosperm phylogeny at either Acorus or Alisma (or Alisma-Triglochin-Potamogeton in one case due to use of a slightly different alignment) and placed the monocots as a basal grade, producing genuine LBA results. These analyses demonstrate that the identification of ANITA as the basalmost extant angiosperms was based on historical signals preserved in the gymnosperm sequences and that the gymnosperms were an appropriate outgroup with which to root the angiosperm phylogeny in the multigene sequence analysis. This strategy of evaluating the appropriateness of an outgroup using artificial sequences and a series of outgroups with increments of divergence levels can be applied to investigations of phylogenetic patterns at the bases of other major clades, such as land plants, animals, and eukaryotes.
Adiposity Compared With Physical Inactivity and Risk of Type 2 Diabetes in Women
Authors: Jamal S. Rana, Tricia Y. Li, JoAnn E. Manson, Frank B. Hu
Journal: Diabetes Care (2006)

OBJECTIVE—The relative contribution of adiposity and physical inactivity to the risk of developing type 2 diabetes remains controversial. RESEARCH DESIGN AND METHODS—We prospectively examined the individual and joint association of obesity and physical activity with the development of type 2 diabetes in 68,907 female nurses who had no history of diabetes, cardiovascular disease, or cancer at baseline. Adiposity was measured by BMI and waist circumference. Physical activity was assessed through average hours of moderate or vigorous exercise and computation of an MET score. RESULTS—We documented 4,030 incident cases of type 2 diabetes during 16 years of follow-up (from 1986 to 2002). In a multivariate model including age, smoking, and other diabetes risk factors, risk of type 2 diabetes increased progressively with increasing BMI (P &amp;lt; 0.001) and waist circumference (P &amp;lt; 0.001) and with decreasing physical activity levels (P &amp;lt; 0.001). In joint analyses of BMI and physical activity, using women who had a healthy weight (BMI &amp;lt;25 kg/m2) and were physically active (exercise ≥21.8 MET h/week) as the reference group, the relative risks of type 2 diabetes were 16.75 (95% CI 13.99–20.04) for women who were obese (BMI ≥30 kg/m2) and inactive (exercise &amp;lt;2.1 MET h/week), 10.74 (8.74–13.18) for women who were active but obese, and 2.08 (1.66–2.61) for women who were lean but inactive. In combined analyses of waist circumference and physical activity, both variables were significant predictors of type 2 diabetes, but the association for waist circumference was substantially stronger than that for physical inactivity. CONCLUSIONS—Obesity and physical inactivity independently contribute to the development of type 2 diabetes; however, the magnitude of risk contributed by obesity is much greater than that imparted by lack of physical activity.
Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. I. Demonstration of similar or identical idiotypes on IgG molecules and T-cell receptors with specificity for the same alloantigens.
Authors: H Binz, H Wigzell
Journal: The Journal of Experimental Medicine (1975)

Antigen-binding receptors on T lymphocytes and IgG antibodies with the same antigen-binding specificity as the T-cell receptors display shared or identical idiotypes. This was shown using a system where adult F1 hybrid rats between two inbred strains were inoculated with T lymphocytes from one parental strain. Such F1 hybrid rats produce antibodies directed against idiotypic determinants present on IgG alloantibodies, produced in the T donor genotype strain and with specificity for the alloantigens of the other parental strain. The idiotypic nature of the F1 antialloantibody serum against the parental alloantibodies was demonstrated both by indirect hemagglutination tests or by gel diffusion using alloantisera with different specificity as targets. Furthermore, the F1 anti-T-lymphocyte sera could be shown to contain antibodies against idiotypic parental T lymphocytes as well. This was shown by the capacity of the antisera, in the presence of complement, to wipe out the relevant parental T-cell reactivity against the other parental strain (as measured in MLC or GVH) whilst leaving the T-lymphocyte reactivity against a third, unrelated allogeneic strain intact. These findings demonstrate that F1 hybrid rats inoculated with parental T lymphocytes make anti-idiotypic antibodies directed against both the T cell receptors and IgG alloantibodies of that parental strain with specificity for alloantigens of the other parental strain. In order to prove identity between the anti-idiotypic antibodies against the B and T-cell antigen-binding molecules the following experiments were carried out; highly purified IgG from relevant alloantibody-containing serum in immunosorbent from could be shown to selectively remove both anti-idiotypic activities from the F1 antiserum. Further more, parental normal T lymphocytes could be shown capable of removing from the anti-idiotypic antisera all those antibodies that would cause agglutination of the relevant alloantibody-coated erythrocytes in the indirect agglutination assay. We would thus conclude that T and B lymphocytes reactive against a given antigenic determinant use receptors with antigen-binding areas coded for by the same variable gene subset(s).
NEONATAL SUPRAVENTRICULAR TACHYCARDIA: RECURRENCE IN THE FIRST YEAR OF LIFE
Authors: William Bonney, Selena R. Levine, Jyoti S. Kandlikar, Akash R. Patel, R. Lee Vogel, Maully J. Shah, Ramesh V. Iyer
Journal: Journal of the American College of Cardiology (2011)
Sequels of Post-operative Urinary Infection in Women
Authors: N. Slade, H. G. Mather, K. B. Linton, H. M. Leather, D. E. B. Powell
Journal: BMJ (1965)

carried out on the hypothesis that pyelonephritis results from recurrent infections of the lower urinary tract (Pinkerton et al., 1961 ;Fry et al., 1962;Cattell et al., 1963 ;Hanley, 1963).The aim of this study was to determine the duration of post- operative urinary infections in women, and the subsequent incidence of recurrent cystitis or pyelonephritis.It forms part of a long-term study of chronic pyelonephritis at these hospitals.Patients Studied Two groups of patients were studied, all of whom had under- gone gynaecological operations followed by post-operative bladder drainage by indwelling catheter for periods of between two and five days.Group 1.-This comprised 73 patients who between 1952 and 1954 had vaginal hysterectomy or pelvic-floor repair by three gynaecologists at one hospital.Post-operative catheter drainage was by an open method, and the bacteriology of the urine was not recorded in detail in some patients.Group 2.-This comprised 109 patients who had vaginal hysterectomy or pelvic-floor repair in 1959 by two gynae- cologists at one hospital.At this time a controlled trial of open and closed methods of bladder drainage was in progress.The bacteriology was well documented, and patients treated by either method have been included in the follow-up. MethodsAll patients were asked to attend for interview by one of the clinicians (N.S., H. G. M., or H. M. L.), at which time a history of urinary tract and cardiovascular symptoms was taken.Physical examination included examination of ocular fundi and the blood-pressure.A urine specimen was obtained by the " tube " method described by Leather and Hutchings (1960).Examination by microscopy for pus cells and by quantitative culture was carried out within two hours of collection, or, when this was not possible, the specimen was stored immediately in the refrigerator.The urine was regarded as infected if it contained at least 100,000 organisms per millitre.Bacterial counts of 10,000/ml.or less were not considered significant, and when counts between 10,000 and 100,000/ml.were obtained a second specimen of urine was cultured.Blood specimens were obtained for haemoglobin, white-cell count, erythrocyte sedimentation rate (Wintrobe method), and blood-urea estimations.Patients in group 1 who were found to have a urinary infec- tion at follow-up were investigated by excretion urography
Risk factors for recurring hepatocellular carcinoma differ according to infected hepatitis virus-An analysis of 236 consecutive patients with a single lesion
Authors: Yukihiro Koike, Yasushi Shiratori, Shinpei Sato, Shuntaro Obi, Takuma Teratani, Masatoshi Imamura, Keisuke Hamamura, Yasuo Imai, Haruhiko Yoshida, Shuichiro Shiina, Masao Omata
Journal: Hepatology (2000)

Patients with hepatocellular carcinoma (HCC) frequently experience intrahepatic HCC recurrence even after complete ablation of primary lesions. Because the oncogenic process may be different for hepatitis B viral (B–viral) and hepatitis C viral (C–viral) HCC, the present study was conducted to elucidate the factors contributing to HCC recurrence with respect to the infected hepatitis virus. Two hundred thirty–six patients with a single HCC lesion who underwent complete ablation of the tumor by PEIT and/or PMCT or surgical resection at Tokyo University and its affiliated hospitals from 1993 to 1997 were enrolled. The patients were classified into 3 groups: the B–viral group, C–viral group, and NBNC group. After complete removal of tumors, the patients were followed for a mean period of 39 months. The factors contributing to HCC recurrence were analyzed by univariate and multivariate analysis using the Cox proportional hazard model. The rate of intrahepatic recurrence in enrolled patients at 1, 3, and 5 years was 19%, 50%, and 64%, respectively. The intrahepatic recurrence rate in C–viral and B–viral HCC was higher than that in the NBNC–related HCC. Fibrosis staging, pathological grading of HCC, and serum AFP levels were significantly linked to intrahepatic recurrence by univariate analysis, and fibrosis staging was strongest in the multivariate analysis for C–viral HCC ( P = .004). In contrast, fibrosis staging did not affect the recurrence in B–viral ( P = .51) and NBNC–related ( P = .77) HCC. Risk factors for HCC recurrence differed according to the infected viral state.
Lowered oesophageal sensory thresholds in patients with symptomatic but not excess gastro-oesophageal reflux: evidence for a spectrum of visceral sensitivity in GORD.
Authors: K C Trimble, A Pryde, R C Heading
Journal: Gut (1995)

Some patients undergoing ambulatory oesophageal pH monitoring to investigate symptoms suggestive of gastro-oesophageal reflux disease (GORD) are found to have oesophageal acid exposure within the physiological range but show a close correlation between their symptoms and individual reflux episodes. It is suggested that these patients might exhibit enhanced oesophageal sensation, akin to the heightened perception of both physiological and provocative stimuli in the gut that has been described in patients with functional gastrointestinal disorders. This study tested the hypothesis by measuring the sensory thresholds for oesophageal balloon distension and discomfort in 20 patients with symptoms of GORD, in whom ambulatory pH monitoring had shown normal acid exposure times, but in whom the symptom index for reflux events was 50% or greater, and compared these with 15 healthy volunteer controls, and with control groups with confirmed excess reflux. The study group showed lower thresholds both for initial perception of oesophageal distension, and for discomfort, compared with healthy controls (median ml (range)); 7.5 (2-19) v 12 (6-30) (p = 0.002) and 10 (5-20) v 16 (8-30) (p &lt; 0.0001), respectively. Sensory thresholds in the study group were also significantly lower than in patients with excess reflux, and than patients with Barrett9s oesophagus, who also exhibited significantly higher sensory thresholds than healthy controls. No differences in sensory thresholds for somatic nerve stimulation were found between the study group and health controls. The results show a spectrum of visceral sensitivity in GORD, with enhanced oesophageal sensation in patients with symptomatic but not excess gastro-oesophageal reflux, suggesting that their symptoms result from a heightened perception of normal reflux events.
Letter: Effects of legal termination and subsequent pregnancy.
Authors: R E Coles, B Tully
Journal: BMJ (1976)

45was systematically covered largely accounts for the fall now occurring in the number of cases of cervical cancer in Aberdeen.In the interests of economy, and in the light of our knowledge of the high-risk groups, should the taking of smears not become part of all routine antenatal care?The majority of cases would then be detected before the high-risk patient had finished childbearing.Twenty years later a fall in the incidence of the disease could be predicted, a fall which will never happen if only the well women offering themselves for screening and rescreening are covered.
Access to Mental Health Services
Authors: John V. Campo, Jeffrey A. Bridge, Cynthia A. Fontanella
Journal: JAMA Pediatrics (2015)

The Surgeon General’s report 2 on mental health called national attention to the public health relevance of pediatric mental disorders, citing encouraging news of an increasing number of evidence-based treatments, as well as the discouraging news that most youth struggling with mental disorders receive no mental health services and that even when services are accessed, they are often inadequate in quality and/or quantity. More than a decade later, still less than half of young people with a mental disorder obtain treatment. 3 Given that mental health and substance use disorders are risk factors for several leading and potentially remediable causes of death, such as accidents, violence, and suicide, this disturbing reality likely has serious consequences for morbidity and mortality in the pediatric- and transitional-aged population. For example, a growing body of evidence indicates that improving access to effective mental health care can reduce suicide risk in young people. 4
Effects of losartan on serum total and high–molecular weight adiponectin concentrations in hypertensive patients with metabolic syndrome
Authors: Toshihiko Uchida, Minoru Shimizu, Yoshihiko Sakai, Tomoki Nakano, Kenji Hara, Kohzo Takebayashi, Teruo Inoue, Koichi Node, Toshihiko Inukai, Kan Takayanagi, Yoshimasa Aso
Journal: Metabolism (2008)
Queries and Minor Notes.
Authors: W. H. Barr
Journal: JAMA (1903)

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