tbuckley/cabot-search huggingface dataset:
American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects
Authors: Joseph R. Carver, Charles L. Shapiro, Andrea Ng, Linda Jacobs, Cindy Schwartz, Katherine S. Virgo, Karen L. Hagerty, Mark R. Somerfield, David J. Vaughn
Journal: Journal of Clinical Oncology (2007)

To review the evidence on the incidence of long-term cardiac or pulmonary toxicity secondary to chemotherapy, radiotherapy, or trastuzumab in symptomatic and asymptomatic cancer survivors. An American Society of Clinical Oncology Panel reviewed pertinent information from the literature through February 2006. Few studies directly addressing the benefits of screening for long-term cardiac or pulmonary toxicity in asymptomatic cancer survivors who received chemotherapy, radiotherapy, or trastuzumab were identified. The reviewed literature included primarily retrospective and cross-sectional studies describing the incidence of cardiac and pulmonary late effects. Anatomic and/or functional abnormalities have been associated with use of all currently available anthracyclines and their derivatives. Trastuzumab-related cardiac dysfunction rarely causes death, and in most cases is reversible with improvement in cardiac function on drug discontinuation and/or treatment with cardiac medications. The estimated aggregate incidence of radiation-induced cardiac disease is 10% to 30% by 5 to 10 years post-treatment, although the incidence may be lower with modern techniques. Radiation pneumonitis is reported in 5% to 15% of lung cancer patients receiving definitive external-beam radiation therapy. A minority of patients may develop progressive pulmonary fibrosis; late complications include cor pulmonale and respiratory failure. Bleomycin-induced pneumonitis is an acute rather than late effect of treatment. Late pulmonary complications in bone marrow or stem cell transplantation patients who develop interstitial pneumonitis include idiopathic pneumonia syndrome and bronchiolitis obliterans. An increased incidence of cardiac and/or pulmonary dysfunction is observed in cancer survivors. Research is needed to identify high-risk patients, and to determine the optimal screening strategies and subsequent treatment.
Gastro-oesophageal reflux prevalence and relationship with bronchial reactivity in asthma
Authors: D Vincent, AM Cohen-Jonathan, J Leport, M Merrouche, A Geronimi, A Pradalier, JC Soule
Journal: European Respiratory Journal (1997)

The relationship between asthma and gastro-oesophageal reflux (GER) is controversial. In an allergy department, GER prevalence was evaluated in asthmatics, with a view to judging the potential influence of GER on asthma. One hundred and five asthmatics were recruited and co-investigated for GER and lung function. Descriptive analysis was performed, patients with (GER+) and without (GER-) GER were then compared, and finally, stepwise regression analysis was used. GER prevalence was 32%. Lung parameters did not differ between GER+ and GER- patients. When restricting analysis to GER+ patients, bronchial reactivity was closely correlated to the number of reflux episodes (NRE) (r=0.983; p=0.001). When comparing patients with more than 15 reflux episodes x day(-1) (n=50), with those having less (n=43), no differences were found in lung function and GER parameters. However, there was a positive correlation between the provocative dose of methacholine causing forced expiration volume to fall 20% from the baseline and NRE in patients with NRE&gt;15 (r=0.561; p=0.05). In conclusion, gastro-oesophageal reflux was observed in a third of the asthma patients studied. These data do not support a firm aetiological relationship between gastro-oesophageal reflux and asthma, but do suggest an association between the number of reflux episodes and bronchial hyperresponsiveness.
National survey of British public's views on use of identifiable medical data by the National Cancer Registry
Authors: Geraldine Barrett, Jackie A Cassell, Janet L Peacock, Michel P Coleman
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objectives</b> To describe the views of the British public on the use of personal medical data by the National Cancer Registry without individual consent, and to assess the relative importance attached by the public to personal privacy in relation to public health uses of identifiable health data. <b>Design</b> Cross sectional, face to face interview survey. <b>Setting</b> England, Wales, and Scotland. <b>Participants</b> 2872 respondents, 97% of those who took part in the Office for National Statistics9 omnibus survey, a national multistage probability sample, in March and April 2005 (response rates 62% and 69%, respectively). <b>Results</b> 72% (95% confidence interval 70% to 74%) of all respondents did not consider any of the following to be an invasion of their privacy by the National Cancer Registry: inclusion of postcode, inclusion of name and address, and the receipt of a letter inviting them to a research study on the basis of inclusion in the registry. Only 2% (2% to 3%) of the sample considered all of these to amount to an invasion of privacy. Logistic regression analysis showed that the proportions not concerned about invasion of privacy varied significantly by country, ethnicity, socioeconomic status, and housing tenure, although in all subgroups examined most respondents had no concerns. 81% (79% to 83%) of all respondents said that they would support a law making cancer registration statutory. <b>Conclusions</b> Most of the British public considers the confidential use of personal, identifiable patient information by the National Cancer Registry for the purposes of public health research and surveillance not to be an invasion of privacy.
Cyclin A/cdk2 Activation Is Involved in Hypoxia-Induced Apoptosis in Cardiomyocytes
Authors: Susumu Adachi, Hiroshi Ito, Mimi Tamamori-Adachi, Yuichi Ono, Toshihiro Nozato, Shinji Abe, Masa-aki Ikeda, Fumiaki Marumo, Michiaki Hiroe
Journal: Circulation Research (2001)

Abstract —Cardiomyocytes are terminally differentiated cells characterized as withdrawal cell-cycle machinery, but nonetheless they are known to express cell-cycle regulators. Because many proteins related to the cell cycle induce apoptosis in proliferating cells, we examined the involvement of these proteins in the apoptosis pathway in cardiomyocytes. Primary rat cardiomyocytes were exposed to a severe hypoxic condition to induce apoptosis. The apoptosis rate of cardiomyocytes increased to ≈40% under 24 hours of hypoxia as evaluated by the TUNEL method. The cyclin A protein level assessed by immunoblot analysis accumulated in a time-dependent manner in cardiomyocytes, but there was no increase in nonmyocytes. Hypoxia increased the activity of cyclin A–associated kinase but not the activity of cyclin E–associated kinase, and the apoptosis was inhibited by infection of dominant-negative cdk2 adenovirus, suggesting that cyclin A and its associated kinase play significant roles in the apoptosis of cardiomyocytes. To investigate the cyclin A–mediated apoptosis, we infected cultured cells with cyclin A adenovirus. Apoptosis was induced in 63±12% of the infected cardiomyocytes in contrast to only 12±3% of the LacZ-infected control cells. In addition, the cells in the hypoxic condition showed an increase in caspase-3 activity and a subsequent decrease in p21 cip1/waf1 protein, which is partly cleaved by caspase-3. These findings confirm that cyclin A–associated kinase mediates hypoxia-induced apoptosis in cardiomyocytes, and they also suggest that additional elements of the cell-cycle–dependent machinery participate in this mechanism.
Assessment of Clinical Validity of a Breast Cancer Risk Model Combining Genetic and Clinical Information
Authors: M. E. Mealiffe, R. P. Stokowski, B. K. Rhees, R. L. Prentice, M. Pettinger, D. A. Hinds
Journal: JNCI Journal of the National Cancer Institute (2010)

BackgroundThe Gail model is widely used for the assessment of risk of invasive breast cancer based on recognized clinical risk factors. In recent years, a substantial number of single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified. However, it remains unclear how to effectively integrate clinical and genetic risk factors for risk assessment.
Bax does not have to adopt its final form to drive T cell death
Authors: Yanan Zhu, Xinqi Liu, David Hildeman, Fred W. Peyerl, Janice White, Elenora Kushnir, John Kappler, Philippa Marrack
Journal: The Journal of Experimental Medicine (2006)

The introduction of antigen into animals causes antigen-specific T cells to divide and then die. Activated T cell death requires either of the death effector molecules, Bak or Bax. When T cells die, Bak and Bax change their conformations, a phenomenon that is thought to be required for Bak or Bax to drive cell death. Here we show that Bak changes conformation before activated T cells die, as detected by an antibody specific for a peptide near the NH2 terminus of Bak, but Bax does not change its shape markedly until after the cells are dead, as detected by an antibody specific for a peptide near the NH2 terminus of Bax. This latter finding is also true in activated T cells that lack Bak and are therefore dependent on Bax to die. This result suggests that Bax does not have to adopt its final, completely unfolded form until after the cells are dead.
A study of urinary excretion of parathyroid hormone in man
Authors: John E. Bethune, Randolph A. Turpin
Journal: Journal of Clinical Investigation (1968)

A procedure for bioassaying parathyroid hormone-like activity in human urine has been developed. 24-hr urine samples were concentrated with dry Sephadex G-25 and bioassayed in the young thyroparathyrocauterized mouse by the measurement of whole blood calcium. Recovery of biological activity and radioiodinated beef parathyroid hormone was over 80%. Normal subjects usually excreted less than 30 U (USP) of activity per day while 18 patients with proven primary hyperparathyroidism excreted a mean of 182 U/day (USP). The activity was not found in 7 patients with hypoparathyroidism or in 5 patients with carcinoma of the breast, but was present in 9 patients with uremia and in 5 with carcinoma of the lung and hypercalcemia.
Bromocriptine inhibits pro-opiomelanocortin mRNA and ACTH precursor secretion in small cell lung cancer cell lines.
Authors: W E Farrell, A J Clark, M F Stewart, S R Crosby, A White
Journal: Journal of Clinical Investigation (1992)

We have previously reported that a human small cell lung cancer (SCLC) cell line (COR L103) that expresses the proopiomelanocortin (POMC) gene and secretes ACTH precursor peptides is relatively resistant to glucocorticoid regulation. Using this model, we have now examined alternative regulatory mechanisms of the POMC gene and found that both the mRNA and ACTH precursor peptides were stimulated four- and two-fold, respectively, after 48 h incubation with db-cAMP. Next, we examined the dopamine agonist, bromocriptine, which acts predominantly through D2 receptors linked to adenyl cyclase to cause a reduction in intracellular cAMP. Bromocriptine suppressed cAMP levels and inhibited precursor peptide secretion within 24 h in a dose-dependent manner (0.15-15 microM). At the highest dose, peptide secretion was inhibited from 95 to 53 pmol/mg protein, and POMC mRNA was reduced by 50%, while beta-actin mRNA remained unchanged. This effect could not be mimicked by incubation of cells with the alpha-adrenergic antagonist, phenoxybenzamine, suggesting that the alpha-adrenergic effects of bromocriptine were not responsible for this observation. These cells also secrete estradiol, but the secretory rate was unaffected by bromocriptine, suggesting, with the beta-actin data, that the POMC inhibition was not a cytotoxic effect. No recovery in precursor peptide secretion was seen in a 48-h period after the removal of bromocriptine. However, when the postchallenge incubation was extended to 8 d, there was a recovery in secretory potential between day 3 and day 8 and normal growth kinetics in the 4 d after removal of the drug. In contrast to these findings, the mouse corticotroph cell line, AtT20, showed no response to bromocriptine, in keeping with reports that this agonist has no effect on anterior lobe corticotrophs. We conclude that bromocriptine effectively inhibits POMC expression in SCLC cells, and that this phenomenon might be of useful clinical application.
Surface charge and hydrophobic properties of fresh and cryopreserved blood phagocytes as determined by partition in two‐phase aqueous polymer systems
Authors: R. S. Hill, R. Norris‐Jones, B. Still, D. E. Brooks
Journal: American Journal of Hematology (1986)

Abstract Cell partitioning in two‐phase aqueous polymer systems was used to examine hydrophobic and surface charge‐related membrane properties of fresh and cryopreserved human blood phagocytes. This technique is highly sensitive to cell surface characteristics, and the partition behavior depends exponentially on the membrane properties involved. The transition from fresh to cryopreserved and reconstituted cells was accompanied by a significant loss of net negative charge without detectable alteration in hydrophobic membrane properties as detected by the partition technique. The partition coefficient (PC), which is the proportion of cells partitioning into the upper phase, when measured for fresh cells mixed with dimethyl sulfoxide (Me 2 SO) and cryopreserved leukocytes. No difference was detected between the PCs of the total leukocytes and phagocytes as determined by differential leukocyte counts of the upper polymer phase. The significantly reduced PC of cells prepared by dextran (Dx) separation in both charge‐sensitive and ‐insensitive systems is attributable to the capacity of Dx to adsorb, in part irreversibly, to cells so that those carrying Dx tend to partition with Dx in the lower phase. These results serve to illustrate the utility of partitioning as a highly sensitive method to probe leukocyte surface membrane properties.
Characterisation of the influence of anti-gastrin, anti-epidermal growth factor, anti-oestradiol, and anti-luteinising hormone releasing hormone antibodies on the proliferation of 27 cell lines from the gastrointestinal tract.
Authors: F Darro, I Camby, A Kruczynski, J L Pasteels, J Martinez, R Kiss
Journal: Gut (1995)

Numerous data from published reports prove that the proliferation of gastrointestinal tumour cell lines are under the control of many hormones or growth factors, or both. Most of these publications report the influence on a very small number of cell lines of one or two such factors only. This work deals with the in vitro characterisation of the influence of the anti-gastrin, the anti-epidermal growth factor (EGF), the anti-oestradiol (E2), and the anti-luteinising hormone releasing hormone (LHRH) antibodies on the proliferation of a large series of gastrointestinal cell lines. Cell proliferation was assessed by means of the colorimetric MTT assay on a series of 27 gastrointestinal cell lines obtained from the American Type Culture Collection (ATCC). Of the 27 cell lines, the anti-gastrin, the anti-EGF, the anti-E2, and the anti-LHRH neutralising antibodies considerably influenced the proliferation of 13, 25, 12, and 16. No gastrointestinal cell line was unresponsive to the four antibodies simultaneously. The anti-gastrin and anti-EGF antibody induced effects on the 27 gastrointestinal cell line proliferation were significantly correlated, as was also the case for the anti-E2 and anti-LHRH antibody induced effects. Of the anti-gastrin, the anti-EGF, the anti-E2, and the anti-LHRH antibodies, it was the anti-EGF one that had the greatest influence, both quantitatively and qualitatively, on gastrointestinal cell proliferation. The correlation of the effects of definite anti-hormone antibodies is suggestive of a common mechanism of action for the corresponding hormones and casts some doubt on the efficiency of anti-hormone monotherapy.
Single Versus Repeated Dosage of the Minor Tranquilizer Chlordiazepoxide (Librium)
Authors: RICHARD I. SHADER, ALBERTO DIMASCIO, JEROLD S. HARMATZ
Journal: American Journal of Psychiatry (1972)

The authors studied the effects of single and repeated doses of medication on the same individuals. They compared the direction of change found after an individual had taken a single dose of medication with that found after he had taken the same drug for one week. When chlordiazepoxide was administered, the direction of change noted after the single dose was indicative of that noted after repeated doses.
Redefining End of Test (EOT) Criteria for Pulmonary Function Testing in Children
Authors: KATHARINE J. DESMOND, PAUL D. ALLEN, DEBBIE L. DEMIZIO, THOMAS KOVESI, ALLAN L. COATES
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

In order for an individual FVC maneuver to be considered acceptable according to the 1994 American Thoracic Society (ATS) standards it must meet end of test (EOT) criteria of a minimum expiration time of 6 s with minimal volume change (0.03 L) over 1 s. We have found that while these criteria are often not met in children, most of the tests do meet the ATS criteria for reproducibility with repeated efforts. We, therefore, sought to develop new EOT criteria that would be more appropriate for children and in keeping with the findings for reproducibility. Using an exponential curve fitting of the volume time tracing, we determined a theoretical curve that closely approximated the actual curve (mean difference between actual and derived FEV1 0.01 ± 0.04 L). The theoretical FVC (FVCFULL) at the point where the curve reached its asymptote was then determined using the fitted curve. Since this point could be difficult to reach for some patients, 95% of FVCFULL (FVC95) was proposed as the new EOT in children. Data from 382 patients were reviewed. Their ages ranged from 5 to 18 yr and their FEV1s from 21 to 120% of predicted. Only 19% of the patients met current ATS EOT requirements despite the fact that 91% met the reproducibility criteria for both FEV1 and FVC. However, 90% of them reached their FVC95. When this was broken down by age, 37% of those ⩽ 7 yr failed to reach FVC95 whereas only 4% of the older children failed to do so. It is proposed that patients be coached to obtain maximal effort and that the curves be individually fitted to an exponential equation to determine whether the patient has achieved EOT as defined by FVC 95.
Cause-effect relationship between the hepatitis C virus and insulin resistance at the time of direct antiviral therapy
Authors: Francesco Negro
Journal: Gut (2010)

Hepatitis C virus (HCV) is a major cause of progressive liver damage, infecting an estimated 3% of the world population. Morbidity and mortality associated with chronic hepatitis C are mainly attributable to progression towards cirrhosis and its end-stage complications. Thus, the main goal of treatment is the prevention of liver disease progression, an objective that can be attained via the eradication of HCV infection with antiviral therapy. The current standard of care consists of a combination of pegylated interferon α (IFNα) and ribavirin, with a cure rate of about 55%. Novel effective direct antiviral agents (DAA), targeting specific viral functions, are expected to be commercially available towards the end of 2011, raising hopes of significant improvements in the cure rates.

An important aspect of HCV infection is its idiosyncratic relationship with the metabolism of glucose,1 which negatively affects liver disease progression and the response to IFNα-based therapies1 while also raising the possibility of multifaceted and clinically relevant interactions with the metabolic syndrome. Although many viral infections induce insulin resistance, the effect of HCV on glucose metabolism is remarkable and supported by a large amount of clinical, epidemiological and experimental data.1 Changes in glucose metabolism are more significant in patients …
Acute-on-chronic liver failure: an early biopsy is essential?
Authors: R. Jalan, R. P. Mookerjee
Journal: Gut (2010)

α-Ketoisocaproate directly inhibits the ATP-sensitive K<sup>+</sup> channel (K<sub>ATP</sub> channel) in pancreatic β-cells, but it is unknown whether direct K<sub>ATP</sub> channel inhibition contributes to insulin release by α-ketoisocaproate and related α-keto acid anions, which are generally believed to act via β-cell metabolism. In membranes from HIT-T15 β-cells and COS-1 cells expressing sulfonylurea receptor 1, α-keto acid anions bound to the sulfonylurea receptor site of the K<sub>ATP</sub> channel with affinities increasing in the order α-ketoisovalerate &lt; α-ketovalerate &lt; α-ketoisocaproate &lt; α-ketocaproate &lt; β-phenylpyruvate. Patch-clamp experiments revealed a similar order for the K<sub>ATP</sub> channel-inhibitory potencies of the compounds (applied at the cytoplasmic side of inside-out patches from mouse β-cells). These findings were compared with the insulin secretion stimulated in isolated mouse islets by α-keto acid anions (10 mM). When all K<sub>ATP</sub> channels were closed by the sulfonylurea glipizide, α-keto acid anions amplified the insulin release in the order β-phenylpyruvate &lt; α-ketoisovalerate &lt; α-ketovalerate ≈ α-ketocaproate &lt; α-ketoisocaproate. The differences in amplification apparently reflected special features of the metabolism of the individual α-keto acid anions. In islets with active K<sub>ATP</sub> channels, the first peak of insulin secretion triggered by α-keto acid anions was similar for α-ketoisocaproate, α-ketocaproate, and β-phenylpyruvate but lower for α-ketovalerate and insignificant for α-ketoisovalerate. This difference from the above orders indicates that direct K<sub>ATP</sub> channel inhibition is not involved in the secretory responses to α-ketoisovalerate and α-ketovalerate, moderately contributes to initiation of insulin secretion by α-ketoisocaproate and α-ketocaproate, and is a major component of the insulin-releasing property of β-phenylpyruvate.
Sequencing of Agents for Metastatic Renal Cell Carcinoma: Can We Customize Therapy?
Authors: Guru Sonpavde, Toni K. Choueiri, Bernard Escudier, Vincenzo Ficarra, Thomas E. Hutson, Peter F. Mulders, Jean-Jacques Patard, Brian I. Rini, Michael Staehler, Cora N. Sternberg, Christian G. Stief
Journal: European Urology (2011)