tbuckley/cabot-search huggingface dataset:
Leukokinetic Studies. XI. Blood Granulocyte Kinetics in Polycythemia Vera, Infection, and Myelofibrosis*
Authors: J. W. Athens, O. P. Haab, S. O. Raab, D. R. Boggs, H. Ashenbrucker, G. E. Cartwright, M. M. Wintrobe
Journal: Journal of Clinical Investigation (1965)
Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2
Authors: Oskar Marín-Béjar, Francesco P Marchese, Alejandro Athie, Yolanda Sánchez, Jovanna González, Victor Segura, Lulu Huang, Isabel Moreno, Alfons Navarro, Mariano Monzó, Jesús García-Foncillas, John L Rinn, Shuling Guo, Maite Huarte
Journal: Genome biology (2013)

Abstract Background The p53 transcription factor is located at the core of a complex wiring of signaling pathways that are critical for the preservation of cellular homeostasis. Only recently it has become clear that p53 regulates the expression of several long intergenic noncoding RNAs (lincRNAs). However, relatively little is known about the role that lincRNAs play in this pathway. Results Here we characterize a lincRNA named Pint (p53 induced noncoding transcript). We show that Pint is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, Pint promotes cell proliferation and survival by regulating the expression of genes of the TGF-β, MAPK and p53 pathways. Pint is a nuclear lincRNA that directly interacts with the Polycomb repressive complex 2 (PRC2), and is required for PRC2 targeting of specific genes for H3K27 tri-methylation and repression. Furthermore, Pint functional activity is highly dependent on PRC2 expression. We have also identified Pint human ortholog ( PINT ), which presents suggestive analogies with the murine lincRNA. PINT is similarly regulated by p53, and its expression significantly correlates with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, PINT is downregulated in colon primary tumors, while its overexpression inhibits the proliferation of tumor cells, suggesting a possible role as tumor suppressor. Conclusions Our results reveal a p53 autoregulatory negative mechanism where a lincRNA connects p53 activation with epigenetic silencing by PRC2. Additionally, we show analogies and differences between the murine and human orthologs, identifying a novel tumor suppressor candidate lincRNA.
Spotting latent infection: the path to better tuberculosis control
Authors: A Lalvani
Journal: Thorax (2003)

The new ELISPOT assay will help control tuberculosis

Tuberculosis (TB) control is based on prevention as well as prompt diagnosis and treatment of active TB. Since the latter is usually accomplished quite effectively in developed countries, and since BCG vaccination is of limited effectiveness, better TB control will require improved diagnosis and preventative treatment of latent tuberculosis infection (LTBI).1–3 The reservoir of latently infected individuals is much larger than the number of active TB cases, and includes recently infected contacts of pulmonary TB cases and immigrants from high prevalence regions who acquired infection in their country of origin. This latter group is becoming increasingly important because over half the burden of TB in many low prevalence countries is carried by immigrants,3–5 and because several higher prevalence countries will soon join the European Union.

Prophylactic treatment of LTBI is highly effective in preventing the subsequent development of active TB;1 the difficulty lies in identifying who is harbouring latent bacilli. TB control programmes rely exclusively on the century old tuberculin skin test (TST) for diagnosing LTBI in asymptomatic individuals with known or suspected TB exposure.1,3 The success or otherwise of TB control and elimination in the developed world thus hinges on the oldest diagnostic test in medicine, and the multiple limitations of the TST constitute a major roadblock to better TB control.

The main drawback of the TST is its poor specificity because of false positive results in BCG vaccinated individuals caused by antigenic cross reactivity of purified protein derivative (PPD) with BCG;6 this confounding effect persists for as long as 15 years after vaccination.7 This is a widespread problem as most of the world’s population is BCG vaccinated and, even in low prevalence countries that have ceased BCG vaccination, most TB cases …
Asthma control in children: Comparison of different lung function parameters
Authors: Insa Korten, Jordis Trischler, Christina Maria Mueller, Christiane Lex
Journal: European Respiratory Journal (2013)

Background: Recently Green et al. reported a lack of agreement among common measures of asthma control in children (FENO, spirometry, asthma control test; Chest 2013; 143: 117-122). In Germany bodyplethysmography is additionally widely used for asthma monitoring. However, its value is still not clear.

Objectives: This study was undertaken to examine agreement between FENO, spirometric and bodyplethysmographic measures and asthma control in children.

Methods: As part of two preceding studies on fractionated breath condensate sampling in asthmatic children we measured exhaled nitric oxide (FENO), FEV1, FEV1/VC, FEF25-75, sRtot, RV/TLC and assessed asthma control in 85 asthmatic children (age 5-17 years). Z-scores for FEV1 and FEF25-75 were calculated with the desktop software by the Global Lung Initiative. Z-scores below -1.645, FEV1/VC   1,0 kPa*s, FENO> 35 ppb, RV/TLC > 0,33 were considered without normal limits, an asthma control test (ACT) score < 20 was considered as uncontrolled asthma. Agreement was analysed between ACT scores and each lung function parameter by kappa statistics.

Results: 22/85 children were classified as uncontrolled asthmatics. Kappa quotients showed slight agreement for asthma control with FEF75-25 (k: 0,105) and no agreement with RV/TLC (0,063), FEV1 (0,051), FEV1/VC (0,015), FENO (0,004), sRtot (-0,08).

Conclusions: Bodyplethysmographic indices were not superior to spirometric parameters in terms of agreement with asthma control.
STUDIES UPON EXPERIMENTAL PNEUMONIA IN RABBITS
Authors: B. S. Kline, M. C. Winternitz
Journal: The Journal of Experimental Medicine (1915)

1. Dead leucocytes are constantly found in the pneumonic exudate. They rapidly undergo disintegration. Up to the seventh day they do not form the majority of the cells of the exudate. 2. Polymorphonuclear leucocytes with vitally stained granules are present in the exudate, vessels, and interstitial tissue of the lung in experimental pneumonia, but they are not demonstrable in the general circulation in the same animals. 3. There is a marked impairment of the circulation in the pneumonic lung. 4. The increase in the intra-alveolar pressure exerted by the exudate has no influence upon the circulation. 5. The impaired circulation results from the wide distribution of capillary fibrin thrombi. In man these are, as a rule, distributed with relative uniformity. In the rabbit this is not usually the case. The thrombi are much more abundant in some areas and may lead to localized necrosis. 6. The impairment of the circulation is of importance in bringing about resolution. Only enough blood is allowed to seep through the vessels to nourish the alveolar walls. Consequently very little serum escapes into the alveoli and the autolysis of the exudate by the leucocytes is unhindered. 7. The impairment of the circulation in the pneumonic lung seriously interferes with the action of intravenous therapy upon the local lesion. 8. The exudate in the pneumonic lung can be readily impregnated with a dye injected intrabronchially. This suggests a method of administration of therapeutic agents in pneumonia.
Reduced Neural Tracking of Prediction Error in Substance-Dependent Individuals
Authors: Jody Tanabe, Jeremy Reynolds, Theodore Krmpotich, Eric Claus, Laetitia L. Thompson, Yiping P. Du, Marie T. Banich
Journal: American Journal of Psychiatry (2013)

Substance-dependent individuals make poor decisions on the Iowa Gambling Task, a reward-related decision-making task that involves risk and uncertainty. Task performance depends on several factors, including how sensitive individuals are to feedback and how well they learn based on such feedback. A physiological signal that guides decision making based on feedback is prediction error. The authors investigated whether disruptions in the neural systems underlying prediction error processing in substance-dependent individuals could account for decision-making performance on a modified Iowa Gambling Task.
Anti-HIV Agent Trichosanthin Enhances the Capabilities of Chemokines to Stimulate Chemotaxis and G Protein Activation, and This Is Mediated through Interaction of Trichosanthin and Chemokine Receptors
Authors: Jian Zhao, Li-Hong Ben, Ya-Lan Wu, Wei Hu, Kun Ling, Shun-Mei Xin, Hui-Ling Nie, Lan Ma, Gang Pei
Journal: The Journal of Experimental Medicine (1999)

Trichosanthin (TCS), an active protein component isolated from a traditional Chinese medicinal herb Trichosanthes kirilowii, has been shown to inhibit HIV infection and has been applied in clinical treatment of AIDS. The recent development that chemokines and chemokine receptors play important roles in HIV infection led us to investigate the possible functional interaction of TCS with chemokines and their receptors. This study demonstrated that TCS greatly enhanced both RANTES (regulated upon activation, normal T cell expressed and secreted)– and stromal cell–derived factor (SDF)-1α–stimulated chemotaxis (EC50 ≅ 1 nM) in leukocytes (THP-1, Jurkat, and peripheral blood lymphocyte cells) and activation of pertussis toxin–sensitive G proteins (EC50 ≅ 20 nM). TCS also significantly augmented chemokine-stimulated activation of chemokine receptors CCR5 and CXCR4 as well as CCR1, CCR2B, CCR3, and CCR4 transiently expressed in HEK293 cells. A mutant TCS with 4,000-fold lower ribosome-inactivating activity showed similar augmentation activity as wild-type TCS. Moreover, flow cytometry demonstrated that the specific association of TCS to the cell membranes required the presence of chemokine receptors, and laser confocal microscopy reveals that TCS was colocalized with chemokine receptors on the membranes. The results from TCS-Sepharose pull-down and TCS and chemokine receptor coimmunoprecipitation and cross-linking experiments demonstrated association of TCS with CCR5. Thus, our data clearly demonstrated that TCS synergizes activities of chemokines to stimulate chemotaxis and G protein activation, and the effects of TCS are likely to be mediated through its interaction with chemokine receptors.
Surgery for Infective Endocarditis
Authors: Bernard D. Prendergast, Pilar Tornos
Journal: Circulation (2010)

I nfective endocarditis (IE) remains a dangerous condition with unchanging incidence and a mortality approaching 30% at 1 year. 1,2Surgery is potentially lifesaving 3 and is required in 25% to 50% of cases during acute infection and 20% to 40% during convalescence. 4 -7 Operative procedures are often technically difficult and associated with high risk, not least because patients are frequently extremely sick with multisystem disease.Nevertheless, indications for surgery are clear in many patients, and international guidelines 8,9 provide strong recommendations that are applicable for the majority.These guidelines are not supported by robust clinical evidence, however, and clinical decision making is often hampered by diverse considerations, including advancing age of the overall patient cohort, the presence of extracardiac complications or preexistent comorbidity, prior antibiotic therapy of varying duration, and the availability of appropriate surgical expertise.In this article, we review the evidence base that supports current clinical practice and attempt to provide recommendations in areas where doubt persists.
Clinical Outcome of ECT in Patients With Major Depression and Comorbid Borderline Personality Disorder
Authors: Ulrike Feske, Benoit H Mulsant, Paul A Pilkonis, Paul Soloff, Diane Dolata, Harold A Sackeim, Roger F Haskett
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Previous research suggests that the comorbidity of major depression with a personality disorder, especially borderline personality disorder, is associated with a poorer response to ECT. The authors compared the acute outcome of ECT in depressed patients with borderline personality disorder, with personality disorders other than borderline personality disorder, and with no personality disorder. METHOD: The study subjects were 139 patients with a primary diagnosis of unipolar major depression and scores of at least 20 on the 24-item Hamilton Depression Rating Scale. Patients were treated with suprathreshold right unilateral or bilateral ECT in a standardized manner and were assessed with the Hamilton depression scale within 3 days and 4–8 days after completing ECT. RESULTS: Compared to patients with personality disorders other than borderline personality disorder (N=42) and those with no personality disorder (N=77), patients with borderline personality disorder (N=20) had less symptomatic improvement assessed up to 8 days after ECT. Patients with personality disorders other than borderline personality disorder responded as well to ECT as those with no personality disorder. Borderline personality disorder patients were more likely to be female and to have medication-resistant depression than the patients in the two comparison groups; they were also younger. However, none of these differences accounted for the borderline personality disorder patients’ poorer response to ECT. CONCLUSIONS: Patients with borderline personality disorder have a poorer acute response to ECT, but explanations for this finding remain elusive.
Decreased Androgen Receptor Levels and Receptor Function in Breast Cancer Contribute to the Failure of Response to Medroxyprogesterone Acetate
Authors: Grant Buchanan, Stephen N. Birrell, Amelia A. Peters, Tina Bianco-Miotto, Katrina Ramsay, Elisa J. Cops, Miao Yang, Jonathan M. Harris, Henry A. Simila, Nicole L. Moore, Jacqueline M. Bentel, Carmella Ricciardelli, David J. Horsfall, Lisa M. Butler, Wayne D. Tilley
Journal: Cancer Research (2005)

Abstract Previously, we reported that androgen receptor (AR), but not estrogen receptor (ER) or progesterone receptor (PR), is predictive of response to the synthetic progestin, medroxyprogesterone acetate (MPA), in a cohort of 83 patients with metastatic breast cancer. To further investigate the role of AR in determining response to MPA in this cohort, we analyzed AR levels by immunohistochemistry with two discrete antisera directed at either the NH2 or the COOH termini of the receptor. Compared with tumors that responded to MPA (n = 31), there was a significant decrease in the intensity and extent of AR immunoreactivity with both AR antisera in tumors from nonresponders (n = 52). Whereas only a single AR immunostaining pattern was detected in responders to MPA, reflecting concordance of immunoreactivity with the two AR antisera, tumors from nonresponders exhibited four distinct AR immunostaining patterns: (a) concordance with the two antibodies (31%), (b) staining only with the COOH-terminal antibody (33%), (c) staining only with the NH2-terminal antibody (22%), or (d) no immunoreactivity with either NH2- or COOH-terminal antibody (14%). DNA sequencing and functional analysis identified inactivating missense gene mutations in the ligand-binding domain of the AR in tumors from two of nine nonresponders positive with the NH2-terminal AR antisera but negative for COOH-terminal immunoreactivity and lacking specific, high-affinity dihydrotestosterone binding in tumor cytosol fractions. Tumors with more AR than the median level (37 fmol/mg protein) had significantly lower levels of PR (30 fmol/mg protein) than tumors with low AR (PR; 127 fmol/mg protein) despite comparable levels of ER. Ligand-dependent activation of the AR in human T47D and MCF-7 breast cancer cells resulted in inhibition of estradiol-stimulated cell proliferation and a reduction in the capacity of the ER to induce expression of the PR. These effects could be reversed using a specific AR antisense oligonucleotide. Increasing the ratio of AR to ER resulted in a greater androgen-dependent inhibition of ER function. Collectively, these data suggest that reduced levels of AR or impaired AR function contribute to the failure of MPA therapy potentially due to abrogation of the inhibitory effect of AR on ER signaling.
Glomerular metalloprotease activity in the aging rat kidney
Authors: J F Reckelhoff, C Baylis
Journal: Journal of the American Society of Nephrology (1993)

Glomerular metalloprotease activity (phenanthroline inhibitable) was measured in cortical homogenates from rat kidneys by use of the rate of degradation of 3H-denatured type I collagen (gelatin). Glomerular metalloprotease activity was similar in male and female kidneys from kidneys from young (4 months) rats (27 +/- 7 and 34 +/- 6 micrograms of [3H]-gelatin degraded/h per milligram of glomerular protein, respectively). Glomerular metalloprotease activity was unaltered by age (18 to 20 months) in intact males but increased two times in old intact females. castrated males, and ovariectomized females. These aging changes correlated inversely with the level of age-dependent glomerular injury, i.e., old intact males had substantially greater glomerular damage than all other old groups. These observations suggest (1) that the androgens are a risk factor for the development of age-dependent glomerular damage: and (2) that an age-dependent increase in glomerular metalloprotease activity may protect against damage by limiting the build-up of glomerular extracellular matrix.
Diet Quality and Survival After Ovarian Cancer: Results From the Women's Health Initiative
Authors: C. A. Thomson, T. E. Crane, B. C. Wertheim, M. L. Neuhouser, W. Li, L. G. Snetselaar, K. M. Basen-Engquist, Y. Zhou, M. L. Irwin
Journal: JNCI Journal of the National Cancer Institute (2014)

Survival after an ovarian cancer diagnosis is poor. Given the high mortality in these patients, efforts to identify modifiable lifestyle behaviors that could influence survival are needed. Earlier evidence suggests a protective role for vegetables, but no prior studies have evaluated overall dietary quality and ovarian cancer survival. The purpose of this analysis was to evaluate the role of prediagnosis diet quality in ovarian cancer survival.
A Ras Homologue Member I Directly Inhibits Signal Transducers and Activators of Transcription 3 Translocation and Activity in Human Breast and Ovarian Cancer Cells
Authors: Arata Nishimoto, Yinhua Yu, Zhen Lu, Xiang Mao, Zhiyong Ren, Stephanie S. Watowich, Gordon B. Mills, Warren S-L. Liao, Xiaomin Chen, Robert C. Bast, Robert Z. Luo
Journal: Cancer Research (2005)

A Ras homologue member I (ARHI) is a novel imprinted tumor suppressor gene whose expression is frequently lost in breast and ovarian cancers. This small GTP-binding protein is a member of the Ras superfamily with significant homology to both Ras and Rap. Unlike the Ras oncogene, however, ARHI inhibits tumor cell growth. To elucidate the mechanisms by which ARHI inhibits cancer growth, we screened a human breast epithelial cell cDNA library using a yeast two-hybrid system for ARHI-interacting proteins. ARHI was found to interact with signal transducers and activators of transcription (STAT) 3, a latent transcription factor that transduces signals from the cell surface to the nucleus and activates gene transcription. STAT3 is frequently phosphorylated and activated in breast and ovarian cancers, where cytokines and growth factors up-regulate STAT3 and stimulate proliferation. The ARHI-STAT3 interaction was confirmed by coimmunoprecipitation in mammalian cells and shown to be specific for STAT3 but not STAT1 or STAT5a. When ARHI and STAT3 were coexpressed in SKOv3 cells, ARHI formed a complex with STAT3 in the cytoplasm and prevented interleukin-6-induced STAT3 accumulation in the nucleus. ARHI markedly reduced STAT3 binding to DNA and STAT3-dependent promoter activity while only moderately affecting STAT3 phosphorylation. Deletion of the NH2 terminus of ARHI significantly compromised its inhibitory activity, suggesting that this unique NH2-terminal extension contributes to ARHI's inhibition of STAT3-mediated transcriptional activity. Thus, the physical association between STAT3 and ARHI as well as the functional inhibition of STAT3 transcriptional activity by ARHI suggests a novel mechanism through which a putative tumor suppressor gene can inhibit STAT3 activity in breast and ovarian cancers.
General practice workload implications of the national service framework for coronary heart disease: cross sectional survey
Authors: J. Hippisley-Cox, M. Pringle
Journal: BMJ (2001)

Standards one to four of the national service framework for coronary heart disease require general practitioners in England to identify all patients with established coronary heart disease or stroke, record their coronary risk factors, and offer appropriate treatment and to identify and treat patients at high risk of developing coronary heart disease. 1 We estimated the general practice workload involved in meeting these goals.
India’s problem with toxic alcohol
Authors: Jeetha D’Silva
Journal: BMJ (2015)

<h3>Background and Objectives</h3> Pediatric strabismus surgery leads to undesirable intraoperative and postoperative side effects that include pain, postoperative nausea and vomiting (PONV), and oculocardiac reflex (OCR). We hypothesized that subtenon anesthesia performed before the start of surgery and combined with general intravenous anesthesia would reduce these adverse effects. <h3>Methods</h3> Forty children (2.5 to 6 years of age, ASA status I to II) were prospectively randomized to receive either subtenon bupivacaine 0.5% or a saline injection before the beginning of surgery in a double-blind manner. Perioperative analgesic requirements, pain scores (CHEOPS scale), hemodynamics, and incidence of OCR and PONV were compared. <h3>Results</h3> Postoperative pain scores were lower (<i>P</i> &lt; .001) at removal of the laryngeal mask and 30 minutes later in the bupivacaine group. Intraoperative and postoperative analgesic requirements were significantly reduced in this group (<i>P</i> &lt; .01). The incidence of OCR and PONV were also significantly decreased (<i>P</i> &lt; .01). Intraoperative values of blood pressure were significantly higher in the saline group at 20 minutes (<i>P</i> &lt; .02). <h3>Conclusion</h3> We conclude that preoperative subtenon bupivacaine 0.5% compared with a saline injection contributed to reduction of perioperative pain and undesirable side effects in pediatric strabismus surgery performed under general anesthesia.