tbuckley/cabot-search huggingface dataset:
Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents
Authors: Nicolai J. Birkbak, Zhigang C. Wang, Ji-Young Kim, Aron C. Eklund, Qiyuan Li, Ruiyang Tian, Christian Bowman-Colin, Yang Li, April Greene-Colozzi, J. Dirk Iglehart, Nadine Tung, Paula D. Ryan, Judy E. Garber, Daniel P. Silver, Zoltan Szallasi, Andrea L. Richardson
Journal: Cancer Discovery (2012)

DNA repair competency is one determinant of sensitivity to certain chemotherapy drugs, such as cisplatin. Cancer cells with intact DNA repair can avoid the accumulation of genome damage during growth and also can repair platinum-induced DNA damage. We sought genomic signatures indicative of defective DNA repair in cell lines and tumors and correlated these signatures to platinum sensitivity. The number of subchromosomal regions with allelic imbalance extending to the telomere (N(tAI)) predicted cisplatin sensitivity in vitro and pathologic response to preoperative cisplatin treatment in patients with triple-negative breast cancer (TNBC). In serous ovarian cancer treated with platinum-based chemotherapy, higher levels of N(tAI) forecast a better initial response. We found an inverse relationship between BRCA1 expression and N(tAI) in sporadic TNBC and serous ovarian cancers without BRCA1 or BRCA2 mutation. Thus, accumulation of telomeric allelic imbalance is a marker of platinum sensitivity and suggests impaired DNA repair.Mutations in BRCA genes cause defects in DNA repair that predict sensitivity to DNA damaging agents, including platinum; however, some patients without BRCA mutations also benefit from these agents. NtAI, a genomic measure of unfaithfully repaired DNA, may identify cancer patients likely to benefit from treatments targeting defective DNA repair.
Acrodermatitis enteropathica with normal zinc concentrations.
Authors: M E Elmes
Journal: Gut (1990)

tion with H pylori (69/70=99%) compared with the smaller risk (RR=8) with antral infection with H pylori (85/96= 89%).'In our series" the frequency of duodenal ulcer in patients with H pylori in their duodenum was double the frequency of ulcers in the duodenums of patients with H pylori in their antra, which is why we suggested 'that duodenal H pylori may be more closely cor- related with duodenal ulceration than is antral infection'.2
RISK FACTORS FOR APPROPRIATE CARDIOVERTER-DEFIBRILLATOR SHOCKS, INAPPROPRIATE CARDIOVERTER-DEFIBRILLATOR SHOCKS, AND MORTALITY IN 549 PATIENTS WITH HEART FAILURE AND IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS
Authors: Wilbert S. Aronow, Harit Desai, Kaushang Gandhi, Chul Ahn, Sadaf Hussain, Hoang M. Lai, Mala Sharma, William H. Frishman, Martin Cohen, Carmine Sorbera
Journal: Journal of the American College of Cardiology (2010)
Choice of Operations in the Management of Symptomatic Sliding Hiatal Hernia
Authors: R Menguy
Journal: Annual Review of Medicine (1972)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Independent association of T cell receptor beta and gamma chains with CD3 in the same cell.
Authors: F Koning, W L Maloy, D Cohen, J E Coligan
Journal: The Journal of Experimental Medicine (1987)

We have demonstrated that the PEER cell line, which expresses a CD3-associated TCR gamma chain on the cell surface, synthesizes TCR beta chain intracellularly. A percentage of this TCR beta chain associates with the CD3 complex intracellularly. These results indicate that TCR beta and gamma chains can be synthesized by one cell line, and that these chains can independently associate with the CD3 complex. However, the results argue against the formation of TCR beta gamma chain complexes in this cell line.
Autophagic Cell Death of Malignant Glioma Cells Induced by a Conditionally Replicating Adenovirus
Authors: Hideaki Ito, Hiroshi Aoki, Florian Kühnel, Yasuko Kondo, Stefan Kubicka, Thomas Wirth, Eiji Iwado, Arifumi Iwamaru, Keishi Fujiwara, Kenneth R. Hess, Frederick F. Lang, Raymond Sawaya, Seiji Kondo
Journal: JNCI Journal of the National Cancer Institute (2006)

Conditionally replicating adenoviruses (CRAds) can be engineered to replicate selectively in cancer cells and cause cancer-specific cell lysis; thus they are considered a promising cancer therapy.To elucidate the mechanisms by which CRAds induce cancer-specific cell death, we infected normal human fibroblasts (MRC5, telomerase negative), human malignant glioma (U373-MG and U87-MG), human cervical cancer (HeLa), and human prostate cancer (PC3) cells (all telomerase positive) with CRAds regulated by the human telomerase reverse transcriptase promoter (hTERT-Ad) or control nonreplicating adenoviruses (Ad-GFP). Nonapoptotic autophagy was assessed in Ad-GFP- and hTERT-Ad-infected cells by examining cell morphology, the development of acidic vesicular organelles, and the conversion of microtubule-associated protein 1 light chain 3 from the cytoplasmic form to the autophagosome membrane form; signaling via mammalian target of rapamycin (mTOR), an autophagy-associated molecule, was monitored by western blot analysis. We also compared the growth of subcutaneous gliomas in nude mice that were treated by intratumoral injection with Ad-GFP or hTERT-Ad. Survival of athymic mice carrying intracranial gliomas treated by intratumoral injection with Ad-GFP or hTERT-Ad was compared by using the Kaplan-Meier method and the Cox-Mantel log-rank analysis. All statistical tests were two-sided.hTERT-Ad induced tumor-specific autophagic cell death in tumor cells and in subcutaneous gliomas. hTERT-Ad-induced autophagy was associated with hTERT-Ad infection kinetics. The mTOR signaling pathway was suppressed in tumor cells and in subcutaneous gliomas treated with hTERT-Ad compared with GFP-Ad or no treatment as shown by reduced phosphorylation of mTOR's downstream target p70S6 kinase (p70S6K). hTERT-Ad treatment of mice (n = 7) slowed growth of subcutaneous gliomas (mean tumor volume = 39 mm3, 95% confidence interval [CI] = 23 to 54 mm3) compared with GFP-Ad treatment (n = 7) (mean tumor volume = 200 mm3, 95% CI = 149 to 251 mm3) at day 7 (volume difference = 161 mm3, 95% CI = 126 to 197 mm3; P < .001). Mice carrying intracranial tumors that were treated with three intratumoral injections of hTERT-Ad survived longer (53 days) than after treatment with GFP-Ad (29 days) (seven mice per group, difference = 24 days, 95% CI = 20 to 28 days; P < .001).hTERT-Ad may kill telomerase-positive cancer cells by inducing autophagic cell death.
Long-Term Disease Free Survival (Dfs) in Patients with Small Breast Cancer: Clinical Relevance of Traditional and New Prognostic Factors in a Retrospective Study
Authors: A. Emiliani, L. Filomeno, A. Iannace, T. Losanno, G. Manna, E. Franzese, F.S. Di Lisa, P. Seminara
Journal: Annals of Oncology (2014)
Effects of sotalol on arrhythmias and electrophysiology during myocardial ischaemia and reperfusion
Authors: W CULLING, W J PENNY, D J SHERIDAN
Journal: Cardiovascular Research (1984)

Isolated, buffer perfused guinea pig hearts were used to study the effects of sotalol on arrhythmias and electrophysiology during 30 min of myocardial ischaemia, induced by reducing coronary flow to 10% of control, and subsequent reperfusion. Action potentials were recorded using the floating microelectrode technique and arrhythmias were noted and defined by extracellular electrical records. Sotalol 10−4 mol·litre−1 reduced the incidence of ventricular arrhythmias during myocardial ischaemia and reperfusion. Prior to the onset of ischaemia sotalol reduced action potential amplitude and V̇max, and prolonged action potential duration, refractory period, and conduction time, and increased pacing threshold. During myocardial ischaemia the effect of sotalol on action potential duration disappeared, and that on refractory period was diminished. The effect of sotalol on action potential amplitude and V̇max was reduced during the early (2 to 12 min) part of ischaemia, but later, at the onset of arrhythmias, tended to reemerge, while the effect on QRS width was exaggerated. Thus the cellular electrophysiological effects of sotalol on normal myocardium provided a poor guide to the mechanism of its antiarrhythmic action in ischaemic tissue.
Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas
Authors: William A. Faubion, M. Eugenia Guicciardi, Hideyuki Miyoshi, Steven F. Bronk, Patricia J. Roberts, Phyllis A. Svingen, Scott H. Kaufmann, Gregory J. Gores
Journal: Journal of Clinical Investigation (1999)

Cholestatic liver injury appears to result from the induction of hepatocyte apoptosis by toxic bile salts such as glycochenodeoxycholate (GCDC). Previous studies from this laboratory indicate that cathepsin B is a downstream effector protease during the hepatocyte apoptotic process. Because caspases can initiate apoptosis, the present studies were undertaken to determine the role of caspases in cathepsin B activation. Immunoblotting of GCDC-treated McNtcp.24 hepatoma cells demonstrated cleavage of poly(ADP-ribose) polymerase and lamin B1 to fragments that indicate activation of effector caspases. Transfection with CrmA, an inhibitor of caspase 8, prevented GCDC-induced cathepsin B activation and apoptosis. Consistent with these results, an increase in caspase 8–like activity was observed in GCDC-treated cells. Examination of the mechanism of GCDC-induced caspase 8 activation revealed that dominant-negative FADD inhibited apoptosis and that hepatocytes isolated from Fas-deficient lymphoproliferative mice were resistant to GCDC-induced apoptosis. After GCDC treatment, immunoprecipitation experiments demonstrated Fas oligomerization, and confocal microscopy demonstrated ΔFADD-GFP (Fas-associated death domain–green fluorescent protein, aggregation in the absence of detectable Fas ligand mRNA. Collectively, these data suggest that GCDC-induced hepatocyte apoptosis involves ligand-independent oligomerization of Fas, recruitment of FADD, activation of caspase 8, and subsequent activation of effector proteases, including downstream caspases and cathepsin B.
Assessment of ability of murine and human anti-lipid A monoclonal antibodies to bind and neutralize lipopolysaccharide.
Authors: H S Warren, S F Amato, C Fitting, K M Black, P M Loiselle, M S Pasternack, J M Cavaillon
Journal: The Journal of Experimental Medicine (1993)

The use of monoclonal antibodies (mAbs) directed to lipid A for the therapy of gram-negative sepsis is controversial. In an attempt to understand their biologic basis of action, we used a fluid-phase radioimmunoassay to measure binding between bacterial lipopolysaccharide (LPS) and two IgM mAbs directed to lipid A that are being evaluated for the treatment of gram-negative bacterial sepsis. Both antibodies bound 3H-LPS prepared from multiple strains of gram-negative bacteria when large excesses of antibody were used, although binding was modest and only slightly greater than control preparations. We also studied the ability of each anti-lipid A antibody to neutralize some of the biological effects of LPS in vitro. Despite large molar excesses, neither antibody neutralized LPS as assessed by the limulus lysate test, by a mitogenic assay for murine splenocytes, or by the production of cytokines interleukin (IL)-1, IL-6, or tumor necrosis factor from human monocytes in culture medium or in whole blood. Our experiments do not support the hypothesis that either of these anti-lipid A mAbs function by neutralizing the toxic effects of LPS.
Stem Cell–like Glioma Cells Promote Tumor Angiogenesis through Vascular Endothelial Growth Factor
Authors: Shideng Bao, Qiulian Wu, Sith Sathornsumetee, Yueling Hao, Zhizhong Li, Anita B. Hjelmeland, Qing Shi, Roger E. McLendon, Darell D. Bigner, Jeremy N. Rich
Journal: Cancer Research (2006)

Malignant gliomas are highly lethal cancers dependent on angiogenesis. Critical tumor subpopulations within gliomas share characteristics with neural stem cells. We examined the potential of stem cell-like glioma cells (SCLGC) to support tumor angiogenesis. SCLGC isolated from human glioblastoma biopsy specimens and xenografts potently generated tumors when implanted into the brains of immunocompromised mice, whereas non-SCLGC tumor cells isolated from only a few tumors formed secondary tumors when xenotransplanted. Tumors derived from SCLGC were morphologically distinguishable from non-SCLGC tumor populations by widespread tumor angiogenesis, necrosis, and hemorrhage. To determine a potential molecular mechanism for SCLGC in angiogenesis, we measured the expression of a panel of angiogenic factors secreted by SCLGC. In comparison with matched non-SCLGC populations, SCLGC consistently secreted markedly elevated levels of vascular endothelial growth factor (VEGF), which were further induced by hypoxia. In an in vitro model of angiogenesis, SCLGC-conditioned medium significantly increased endothelial cell migration and tube formation compared with non-SCLGC tumor cell-conditioned medium. The proangiogenic effects of glioma SCLGC on endothelial cells were specifically abolished by the anti-VEGF neutralizing antibody bevacizumab, which is in clinical use for cancer therapy. Furthermore, bevacizumab displayed potent antiangiogenic efficacy in vivo and suppressed growth of xenografts derived from SCLGC but limited efficacy against xenografts derived from a matched non-SCLGC population. Together these data indicate that stem cell-like tumor cells can be a crucial source of key angiogenic factors in cancers and that targeting proangiogenic factors from stem cell-like tumor populations may be critical for patient therapy.
Disability Pension for Major Depression in Finland
Authors: E T Isometsä, H Katila, T Aro
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors' goal was to investigate the treatment received before receipt of a disability pension for major depression in a representative sample of depressed patients. METHOD: The medical statements for a random sample of 277 subjects drawn from the Disability Pension Register of the Social Insurance Institution were examined. The subjects selected represented individuals in Finland who were granted a disability pension because of DSM-III-R major depression during a 12-month period in 1993–1994. RESULTS: For 254 (92%) of the subjects, the statements regarding pension eligibility were written either by a psychiatrist or a psychiatric resident for patients who were currently being treated in psychiatric settings. There was an additional diagnosis of a comorbid mental disorder or a somatic disease contributing to disability in two-thirds of the statements. Overall, the statements indicated that 242 (87%) of the subjects were prescribed antidepressant medication, but only 24 (9%) received weekly psychotherapy, and only 11 (4%) received ECT. CONCLUSIONS: Most subjects granted a disability pension for major depression in Finland have comorbid mental or physical disorders contributing to their disability. Before receiving their pension, most received antidepressant treatment, but few received the established nonpharmacological treatments.
The domain structure and retrotransposition mechanism of R2 elements are conserved throughout arthropods
Authors: W. D. Burke, H. S. Malik, J. P. Jones, T. H. Eickbush
Journal: Molecular Biology and Evolution (1999)

R2 elements are non-LTR retrotransposons that insert in the 28S rRNA genes of arthropods. Partial sequence data from many species have previously suggested that these elements have been vertically inherited since the origin of this phylum. Here, we compare the complete sequences of nine R2 elements selected to represent the diversity of arthropods. All of the elements exhibited a uniform structure. Identification of their conserved sequence features, combined with our biochemical studies, allows us to make the following inferences concerning the retrotransposition mechanism of R2. While all R2 elements insert into the identical sequence of the 28S gene, it is only the location of the initial nick in the target DNA that is rigidly conserved across arthropods. Variation at the R2 5' junctions suggests that cleavage of the second strand of the target site is not conserved within or between species. The extreme 5' and 3' ends of the elements themselves are also poorly conserved, consistent with a target primed reverse transcription mechanism for attachment of the 3' end and a template switch model for the attachment of the 5' end. Comparison of the approximately 1,000-aa R2 ORF reveals that it can be divided into three domains. The central 450-aa domain can be folded by homology modeling into a tertiary structure resembling the fingers, palm, and thumb subdomains of retroviral reverse transcriptases. The carboxyl terminal end of the R2 protein appears to be the endonuclease domain, while the amino-terminal end contains zinc finger and c-myb-like DNA-binding motifs.
Mindfulness-based stress reduction in patients with interstitial lung disease: A pilot study
Authors: Giacomo Sgalla, Roberto Ferrari, Stefania Cerri, Maria Pia Ricchieri, Margherita Ori, Martina Garuti, Gloria Montanari, Sofia Taddei, Fabrizio Luppi, Richeldi Luca
Journal: European Respiratory Journal (2014)

Interstitial lung diseases (ILDs) are characterized by a chronic and progressive course with reduced quality of life (QoL). Depressive symptoms are common and persistent in patients with ILD.  Mindfulness-based stress reduction (MBSR) is a protocol integrating Buddhist meditation with contemporary clinical and psychological practice; MBSR has already proven to reduce negative moods related to chronic symptoms.  Nineteen ILD patients (M=11, mean age ± SD: 65 ± 8 years; 12 affected by idiopathic pulmonary fibrosis) were enrolled in a prospective, open-label, observational study evaluating feasibility, safety, and effect on QoL and lung function of a MBSR program. The intervention consisted of 8 weekly group meetings and 45 minutes-long daily home training. Three quarterly group meetings were added in the follow-up. Outcomes included change in Shortness Of Breath Questionnaire (SOB), Cough And Sputum Assessment Questionnaire (CASA-Q), Profile Of Mood State (POMS) test, Perceived Stress Scale (PSS), pulmonary function tests and 6-minutes walking test between enrolment, end of intervention and end of 1-year follow-up.  Two patients (10.5%) dropped out early for non-respiratory causes (low back pain and chronic fatigue, respectively). Adherence to the program was 89%. A statistically significant reduction in POMS total score and in the rage and irritability components of the PSS test was observed (pl0.05). Other questionnaire scores and pulmonary function parameters did not show significant change over time.  These results suggest that a MBSR program is feasible and safe in ILD patients. The observed reduction in negative moods lends support to the design of confirmatory larger controlled trials.
Diagnosis of respiratory viral infections in cystic fibrosis by PCR using sputum samples
Authors: A.M. Jones, W. Flight, B. Isalska, M. Cullen, K. Mutton, A. Bowling, D. Riley, K. Webb, R. Bright-Thomas
Journal: European Respiratory Journal (2011)

To the Editors:

Recent epidemics of virulent respiratory viruses, such as H1N1 influenza and severe acute respiratory syndrome coronavirus (SARS-CoV), have highlighted the clinical importance of methods for the rapid and accurate detection of respiratory virus infection [1, 2]. A diagnosis of a respiratory viral infection may have implications for infection control measures and treatment of patients [3]. Molecular-based techniques offer a more rapid and sensitive method for diagnosis of respiratory viral infection than viral culture or serology [4]. PCR-based methods can be applied to nasal and/or throat swab samples for the rapid detection of common respiratory viruses [5]. As the majority of adults with cystic fibrosis (CF) produce sputum during infective exacerbations, we investigated whether sputum is a suitable medium for the diagnosis of respiratory viral infections in patients with CF using a PCR method, by comparing results …
Orthotopic Implantation of Human Hepatocellular Carcinoma in Mice
Authors: Carolina Armengol, Gemma Tarafa, Loreto Boix, Manel Solé, Rosa Queralt, Dolors Costa, Oriol Bachs, Jordi Bruix, Gabriel Capellá
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To allow the longitudinal investigation of molecular events associated with the progression of human hepatocellular carcinoma (HCC), we sought to develop a murine model by orthotopic implantation of tumor fragments obtained from patients diagnosed at early stage. Experimental Design: Tumor pieces (2 × 2 mm) were implanted on the liver surface of nu/nu mice. After xenograft growing, subsequent passages were performed to achieve long-term implant viability. Isolation of tumoral hepatocytes was done to establish new cell lines. HCC characteristics, proliferation rate, apoptotic index (terminal deoxynucleotidyl transferase-mediated nick end labeling), and expression of cell-cycle regulators (cyclins E and A, p21Cip1, p27Kip1, p16INK4a, pRb, and p53) were assessed by Western Blot and immunohistochemistry, to correlate them with tumor progression. Results: Five (50%) of the 10 primary HCCs resulted in small slow-growing liver implants. Three of them are viable after 48 months, whereas the remaining two survived for 15 and 13 months. Xenografts throughout passages exhibited a more aggressive phenotype with a poorer degree of differentiation, intense proliferation, moderate apoptosis, cell-cycle deregulation, p53 alterations, microvascular invasion, and dissemination. In one single passage, we observed critical growth delay, which was associated with significant p27kip1 overexpression. We established the anchor-free growing BCLC-9 cell line from one xenograft. This has gains of chromosomes 7, 5p, 6q, and 9q, is hepatitis B virus-DNA positive, does not secrete α-fetoprotein, and has TP53 missense mutations in codons 192 and 242. Conclusions: The orthotopic implantation of early HCC fragments in nude mice provides a useful model to investigate the mechanisms of human HCC evolution and to establish new cell lines.
Three other motivational factors
Authors: Kent Bach
Journal: Behavioral and Brain Sciences (2005)

Ainslie uses his hyperbolic discount model to explain a dazzling array of puzzling motivational phenomena. In so doing, he assumes that the motivational force of a given option at a given time is directly proportional to its discount-adjusted reward as assessed at that time. He overlooks three other factors which, independently of the perceived reward, can affect motivational force.
Metformin for Weight Loss in Pediatric Patients Taking Psychotropic Drugs
Authors: John A Morrison, Elizabeth M Cottingham, Bruce A Barton
Journal: American Journal of Psychiatry (2002)

Metformin was assessed as a treatment for weight gain in children taking olanzapine, risperidone, quetiapine, or valproate.The subjects were 19 patients aged 10-18 years; 15 were white and four were black, and there were 12 boys and seven girls. In a 12-week open-label study, each patient received metformin, 500 mg t.i.d. Changes in weight and body mass index were evaluated by using repeated measures analysis of variance.Of the 19 patients, 15 lost weight, three gained 1.6 kg or less, and one had no change. The mean changes in weight and body mass index at 12 weeks were highly significant.Metformin merits further study as a treatment for weight gain in patients taking psychotropic medications.