tbuckley/cabot-search huggingface dataset:
Different uptake mechanisms may influence tumor selectivity of 5-aminolevulinic acid (ALA) and ALA-ester induced protoporphyrin IX (PPIX)
Authors: Rene C. Krieg, Dominik Uihlein, Kristina Schwamborn, Ruth Knuechel
Journal: Cancer Research (2006)

618   Aim: Clinical application of 5-aminolevulinic acid (ALA) results in a tumor specific accumulation of the heme precursor protoporphyrin IX (PPIX). This selectivity can be used either to sensitively detect - photodynamic diagnosis (PDD) - or to effectively treat - photodynamic therapy (PDT). Techniques are clinically established and widely used. However little is known about the final cause to generate tumor specificity. Besides metabolism the cellular ALA-uptake is discussed. Therefore we analyzed the influence of transmembrane transport on ALA-uptake. Methods: Human cell lines (CCD18, HT29) with different degrees of differentiation were cultured in plateau phase, incubated with ALA or ALA-ester (methyl, benzyl, hexyl), respectively. Cells were harvested and PPIX-content was measured by flow cytometry. A co-incubation with amino acids (beta-alanine, GABA, taurine (competitive inhibition)) and hypotaurine (inhibitor of BETA-transporter) was performed to elucidate for uptake pathways. In addition the incubation temperature was altered (4, 20, 37, 40) to distinguish between active transport/passive diffusion via the Arrhenius plot. Prior experiments (MTT-tests) showed that neither reagents nor temperature used were toxic to the cells. Results: HT29 showed a much higher PPIX content than CCD18, reflecting tumor specificity observed in vivo. Hypotaurin (1-15 mM) reduced ALA-induced PPIX accumulation down to 75 % (CCD18) and to 35 % (HT29), but had no influence onto ester mediated PPIX. The competitive inhibition by amino acids (15 mM) decreased PPIX content in CCD18 down to 60 % (ALA) and 50 % (ALA-esters). For HT29 PPIX accumulation was decreased down to 40 % (ALA) and 85 % (ALA-esters). Analyzing the Arrhenius plot reveals activation energies for trans-membrane crossing: CCD18: 15 kJ/mol (ALA + esters). HT29: 10-80 kJ/mol (ALA, temperature dependent), 20 kJ/mol (all esters). Values below 17 kJ/mol are affiliated with passive diffusion, above 32 kJ/mol with active transportation, respectively. Conclusions: Inhibition of BETA-transporters by either hypotaurine (direct) or special amino acids (competitive) reveals ALA for HT29 to be transported predominantly by active BETA transporter, whereas the esters are entering the cell by passive diffusion. CCD18 seems to transport ALA via BETA transporter to a much lower extent. With respect to activation energies, active transportation in HT29 is proven, whereas for CCD18 passive diffusion is confirmed.
Aortic Valve Replacement for Low-Flow/Low-Gradient Aortic Stenosis
Authors: Franck Levy, Marcel Laurent, Jean Luc Monin, Jean Michel Maillet, Agnès Pasquet, Thierry Le Tourneau, Hélène Petit-Eisenmann, Mauro Gori, Yannick Jobic, Fabrice Bauer, Christophe Chauvel, Alain Leguerrier, Christophe Tribouilloy
Journal: Journal of the American College of Cardiology (2008)
Corticosteroid cross-reactivity: clinical and molecular modelling tools
Authors: M. Baeck, J. A. Chemelle, A. Goossens, J. F. Nicolas, R. Terreux
Journal: Allergy (2011)

To cite this article: Baeck M., Chemelle J.A., Goossens A., Nicolas J.F., Terreux R. Corticosteroid cross-reactivity: clinical and molecular modelling tools. Allergy 2011; 66: 1367–1374. Background: Corticosteroids have been classified into following four cross-reacting groups in function of their contact-allergenic properties: A, B, C and D, the last subdivided into D1 and D2. Recent data indicate that C16-methylated and nonmethylated molecules need to be distinguished, the latter selectively binding with arginine to form stable cyclic adducts and producing considerably more positive reactions than the former. This study compares molecular modelling and patch-test results to determine cross-reactivity patterns. Methods: The patch-test results obtained with 66 corticosteroid molecules in 315 previously sensitized subjects were analysed and correlated with modelling and clustering in function of the electrostatic and steric fields of these molecules. Results: The classification obtained after in silico hydrolysis of C21 and C17 esters was selected with an optimal cut into three clusters: the patients who reacted positively to cluster 2 (halogenated molecules from group B, with C16/C17 cis ketal or diol structure) and cluster 3 (halogenated molecules from groups C and D1, C16-methylated) also reacted to cluster 1 (molecules mostly from groups A and D2, without C16-methyl substitution or halogenation and budesonide). The reverse, however, was not the case. Conclusion: Two patient profiles with probably different areas of immune recognition are identified as follows: the profile 1 patients were allergic to the frequently positively reacting cluster 1 only, for whom electrostatic fields (molecular charge) seem important; the profile 2 patients reacted to clusters 1 and 2 and/or 3, for whom steric fields (structure) are determinant and who probably presented a global recognition of the corticosteroid skeleton. A modified classification is thus proposed.
Abstract 210: {alpha}MyHC-mCherry-LC3 Transgenic Mice is a New and Useful Tool to Examine the Role of Autophagy in Cardiomyocytes
Authors: Mai Terada, Kiyoshi Nobori, Yoshiko Munehisa, Manabu Kakizaki, Takayoshi Ohba, Takashi Koyama, Yoichiro Takahashi, Masaru Ishida, Kenji Iino, Toshimitsu Kosaka, Hiroyuki Watanabe, Hitoshi Hasegawa, Hiroshi Ito
Journal: Circulation (2008)
Cross‐reacting IgE and IgG antibodies to <i>Pityrosporum ovale</i> mannan and other yeasts in atopic dermatitis
Authors: P. Lintu, O. Kortekangas‐Savolainen, K. Kalimo, J. Savolainen, E.O. Terho, P. Lintu, M. Nermes
Journal: Allergy (1999)

Atopic dermatitis (AD) patients often demonstrate positive skin prick test results and serum IgE antibodies to a range of different yeasts. This has been thought to be due to cross‐reactivity. In this study, the cross‐reactivity of IgE and IgG antibodies between mannan and crude antigens of Pityrosporum ovale , Candida albicans , and Saccharomyces cerevisiae and crude antigens of Cryptococcus albidus and Rhodotorula rubra was examined by RAST and ELISA inhibition with two serum pools of AD patients. We found cross‐reacting IgE and IgG antibodies. In the IgE response, the main cross‐reacting pattern was the mannan region, although inhibition could be achieved also with crude antigens of C. albicans , S. cerevisiae , and, to some extent, C. albidus . P. ovale was the most potent inhibitor of IgE‐binding components, and against it the highest IgE antibody levels were detected in AD serum pools. In contrast, C. albicans was found to be the most important inducer of IgG antibodies, since the IgG level against P. ovale mannan in both AD serum pools was very low. Cross‐reacting antibodies were also seen in ELISA inhibition with both crude and mannan antigens, but since the IgG antibody level of P. ovale mannan in AD serum pools was low, further studies are needed to confirm the IgG results.
Psychiatric and nonmedical decisions on commitment
Authors: M J Badger, J H Shore
Journal: American Journal of Psychiatry (1980)

The civil commitment statutes of Oregon were changed in 1973 and 1975 to include nonphysician court examiners and public prosecutors in the commitment hearing. To evaluate the effect of these changes the authors compared the commitment decisions actually made by panels composed of two physicians with those made by panels with one physician and one nonphysician mental health professional. They also compared the commitment decisions made by six groups of medical and nonmedical people involved with the commitment process regarding five case vignettes. They found that decisions made by the nonmedical mental health professionals were not significantly different from those made by the psychiatric examiners.
LSC 2013 abstract - Upregulation of IgA synthesis in COPD through TACI
Authors: Maha Zohra Ladjemi, Marylène Lecocq, Birgit Weynand, Holly Bowen, Bruno Detry, Charles Pilette
Journal: European Respiratory Journal (2013)

Background  The prevalence of exertional hypoxemia (EH) in unselected COPD patients is unknown. Hypoxia leads to adrenomedullin (ADM) upregulation through the HIF-1 pathway. We hypothesize that ADM might be associated with EH in COPD. Adding ADM to clinical variables might improve EH prediction   Methods  1233 6MWTs from 574 patients with clinically stable COPD II - IV enrolled in an investigator initiated, multinational, prospective, longitudinal, observational cohort were analyzed. EH was defined as an arterial SaO 2  ≤ 88% measured during 6MWT   Findings  EH was observed in 27.3%, 28.5% and 28.4% at baseline, 1 and 2 years FU. EH was common in GOLD IV (54%) but not infrequent in III (38.8%) and II (15.1%). Patients presenting EH had a longer duration of the disease, more dyspnoea, poorer health-related QoL, shorter 6 MWD, higher HR, and increased ADM. EH was associated with greater deterioration of the health-related QoL (SGRQ activity score ,p=0.038) and SF-36 (physical function, p=0.034), higher severe exacerbation (p=0.006) and death (p=0.02) annual rates. In the UV analysis, MMRC, 6MWD, FEV1% pred, and ADM but not age and Charlson score were associated with EH. In the MV analysis, besides FEV1%pred (p X  2  11.97, p=0.0005), NRI 95% CI (7.4%, p=0.015). Patients with preserved FEV1 (>50%) but high ADM levels (>1nmol/l) presented increased risk (40%) for EH   Conclusion:  Exertional desaturation is common and associated with poorer clinical outcomes in stable COPD. ADM improves prediction of exertional desaturation.
Abstract 11959: Cardiac Denervation Appears Before Becoming Myocardial Tissue Fibrosis in Patients With Cardiac Involvement Sarcoidosis and Active Inflammation Using C-11 Hydroxyephedine PET/CT and Cardiac Magnetic Resonance
Authors: Keiichiro Yoshinaga, Ichizo Tsujino, Osamu Manabe, Yuuki Tomiyama, Takahiro Sato, Noriko Oyama-Manabe, Hiroshi Ohira, Ken-ichi Nishijima, David Birnie, Rob S Beanlands, Masaharu Nishimura, Nagara Tamaki
Journal: Circulation (2014)

Background: Cardiac involvement sarcoidosis (CS) has increased risk of arrhythmia linked to sudden death. Cardiac sympathetic nervous (SNS) dysfunction may play an important role for these events. However, the association between the SNS dysfunction and active inflammation or tissue fibrosis has not been studied. The aim of this study was to evaluate the left ventricle (LV) SNS dysfunction measured by C-11 hydroxyephedrine (HED) positron emission tomography (PET)/CT and its association with tissue fibrosis measured by cardiac magnetic resonance (CMR) in patients with CS and active inflammation. Methods: Eleven patients with CS based on the JMHW guidelines (1993) were enrolled. CS (age 59±16 y) and preserved LVEF (64±14 %) underwent HED PET, FDG PET, and CMR. Ten healthy controls underwent HED PET. LV wall was divided into 17 segments. Reduced HED uptake, focal FDG uptake, and late gadolinium enhancement (LGE) on CMR were defined as positive for the visual assessment. In addition, whole LV and regional HED uptake was quantitatively assessed by retention index (RI). Standard uptake value (SUV) was measured in the FDG positive segments. Results: CS had reduced global LV HED RI compared to control (0.09±0.04 vs. 0.15±0.03 %/min, P&lt;0.001). FDG positive group (n=7) had lower global HED RI than FDG negative group (n=4) (0.065±0.027 vs. 0.130±0.040 %/min, P=0.010). In contrast, there was no significant difference in LGE positive segments numbers between the two groups (3.14±2.79 vs. 1.25±0.96, P=0.46). In segmental analysis, the percentage of abnormal segments were trend to higher in HED than LGE (P=0.19). In addition, there was no correlation between regional FDG SUV and HED RI (n=42 segments, R=-0.11, P=0.50). Conclusions: Cardiac involvement sarcoidosis with active LV inflammation and preserved LVEF showed global LV cardiac sympathetic nervous dysfunction. Denervation area was tended to be larger than tissue fibrosis. Furthermore, no association was seen between FDG uptake and HED retention index in regional level. These findings may imply that multiple factors other than inflammatory process and tissue fibrosis may be involved in the cardiac sympathetic nervous dysfunction in cardiac involvement sarcoidosis.
CD11c <sup>+</sup> Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via Interleukin-17A
Authors: Rupert Oberhuber, Timm Heinbokel, Hector Rodriguez Cetina Biefer, Olaf Boenisch, Karin Hock, Roderick T. Bronson, Markus J. Wilhelm, Yoichiro Iwakura, Karoline Edtinger, Hirofumi Uehara, Markus Quante, Floris Voskuil, Felix Krenzien, Bendix Slegtenhorst, Reza Abdi, Johann Pratschke, Abdallah Elkhal, Stefan G. Tullius
Journal: Circulation (2015)

Organ transplantation has seen an increased use of organs from older donors over the past decades in an attempt to meet the globally growing shortage of donor organs. However, inferior transplantation outcomes when older donor organs are used represent a growing challenge.
Multiple personality disorder in The Netherlands: a clinical investigation of 71 patients
Authors: S Boon, N Draijer
Journal: American Journal of Psychiatry (1993)

The aim of this study was to describe the phenomenology of multiple personality disorder as presented in a group of Dutch patients.Seventy-one patients with multiple personality disorder were interviewed with the Dutch version of the Structured Clinical Interview for DSM-III-R Dissociative Disorders (SCID-D); following the SCID-D, the Structured Trauma Interview was administered. Before the interview, patients completed the Dissociative Experiences Scale.The presenting characteristics of the patients showed a striking resemblance to those in several large North American series. Patients had spent an average of 8.2 years in the mental health system prior to correct diagnosis. Patients presented with many different symptoms and frequently received other psychiatric or neurological diagnoses. A history of childhood physical and/or sexual abuse was reported by 94.4% of the subjects, and 80.6% met criteria for posttraumatic stress disorder.Patients with multiple personality disorder have a stable set of core symptoms throughout North America as well as in Europe. To improve the detection of patients at high risk for multiple personality disorder, standardized instruments for inquiry about dissociative pathology should be used as part of routine diagnostic assessment.
Effects of a 3-week inpatient pulmonary rehabilitation (PR) on activity parameter in patients with COPD
Authors: Inga Heinzelmann, Stella Seeberg, Katrin Beutel, Klaus Kenn
Journal: European Respiratory Journal (2012)

Rationale:   Physical activity (PA) level in patients with COPD is markedly reduced in comparison to elderly healthy people. The aim of this study was to investigate the effect of a 3-week inpatient rehabilitation program (PR) on activity parameter measured by SenseWear®.   Methods:   Forty patients with COPD, stage III-IV (age: 62±5y; BMI: 26±5kg/m 2 ; FEV 1 : 36±9%pred.) were included in this prospective trial. PA was measured by SenseWear® Armband in all patients for 3 days at the beginning and at the end of inpatient PR. Additionally, quality of life was requested by SF36 questionnaire and each patient performed a 6-minute walking test (6MWT) (after pretest) pre and post PR.   Results:   6MWD improved significantly following PR (+39.1 [95% CI, +69 to +8] p=0.01). We observed an increase in mental score of SF36 (+5.10 [95%CI, +9.8 to +0.4] p=0.03). No significant differences between PA parameter pre and post PR were found: total energy expenditure (+35.27±319kcal, p=0.49), steps per day (+293±1419, p=0.20), metabolic rate (-0.01±0.28, p=0.78), duration of PA more than 3fold basic metabolic rate (-4.9±74, p=0.63) were seen. There was no significant difference in PA data between 24 hours calculated as the mean of 3 days compared to the PA data of the first 24 hours of the 3 day measurement.   Conclusions:   These data show that there are no relevant changes in PA following inpatient PR, although exercise capacity and quality of life are improved. We hypothesize that an inpatient setting predefines the daily amount of PA that is not similar to the activity chosen in daily life at home. We conclude that PA measurement may not be appropriate as an outcome parameter for an inpatient PR.
A positive screening test for an untreatable condition provides psychological relief from uncertainty
Authors: T. Marteau, S. Michie
Journal: BMJ (1995)

H pylon is common,6 this is not yet well estab- lished, and the article by Bytzer et al cannot be considered a serious evaluation of the cost effectiveness of such a policy.Studies to address this important question will also have to take into consideration some of the less tangible benefits of a "negative" result on endoscopy.
What makes a good psychiatrist? A survey of clinical tutors responsible for psychiatric training in the UK and Eire
Authors: DINESH BHUGRA, KANDIAH SIVAKUMAR, GARETH HOLSGROVE, GEORGIA BUTLER, MORVEN LEESE
Journal: World Psychiatry (2009)

The characteristics of a good psychiatrist practising in the UK health services have been described in policy but not in practice. We set out to determine what key characteristics are required for an individual to be identified as a good psychiatrist to become a member of the Royal College of Psychiatrists. A postal survey of all clinical tutors responsible for psychiatric training in the UK and Eire was carried out. These tutors are approved by the Royal College of Psychiatrists. 113 tutors responded (out of 163, 69.3% return). The most important identified characteristic was overall competency in diagnosis, management and investigations (98%) and the least desirable was ability to appraise staff (13%). With recent changes in training and assessment in the UK, further surveys of this kind are indicated to understand the trainers' views, and should be extended also to trainees.
Childhood sexual, physical, and psychological abuse in bulimia nervosa
Authors: M Rorty, J Yager, E Rossotto
Journal: American Journal of Psychiatry (1994)

This study sought to determine if rates of childhood sexual, physical, psychological, and multiple abuse (i.e., abuse in more than one form) differed between women with a lifetime history of bulimia nervosa and women with no history of eating disorders.Subjects were 80 women, aged 18-35, with a lifetime history of bulimia nervosa (40 women who had recovered for a year or more and 40 women currently suffering from bulimia nervosa) and 40 women who had never had an eating disorder or related difficulties. The cohort was obtained primarily by newspaper advertisement. Subjects participated in structured diagnostic interviews and completed paper-and-pencil questionnaires related to abusive experiences in childhood.Women in the bulimia nervosa group reported higher levels of childhood physical, psychological, and multiple abuse. Contrary to expectation, rates of sexual abuse did not distinguish the groups, except in combination with other forms of abuse.The higher rates of psychological, physical, and multiple abuse found among women with a lifetime history of bulimia nervosa than among comparison subjects underscore the importance of examining the full range of possible abusive experiences in women with eating disorders, rather than focusing simply on sexual abuse.
GPs are not so bad at diagnosis
Authors: Tony Kendrick
Journal: BMJ (2008)

<h3>Background</h3> Palliative sedation is defined as deliberately lowering a patient’s consciousness, to relieve intolerable suffering from refractory symptoms at the end of life. Palliative sedation is considered a last resort intervention in end-of-life care that should not be confused with euthanasia. <h3>Aim</h3> To inform healthcare professionals about attitudes of the general public regarding palliative sedation. <h3>Design and setting</h3> A cross-sectional survey among members of the Dutch general public followed by qualitative interviews. <h3>Method</h3> One thousand nine hundred and sixty members of the general public completed the questionnaire, which included a vignette describing palliative sedation (response rate 78%); 16 participants were interviewed. <h3>Results</h3> In total, 22% of the responders indicated knowing the term ‘palliative sedation’. Qualitative data showed a variety of interpretations of the term. Eighty-one per cent of the responders agreed with the provision of sedatives as described in a vignette of a patient with untreatable pain and a life expectancy of &lt;1 week who received sedatives to alleviate his suffering. This percentage was somewhat lower for a patient with a life expectancy of &lt;1 month (74%, <i>P</i> = 0.007) and comparable in the case where the physician gave sedatives with the aim of ending the patient’s life (79%, <i>P</i> = 0.54). <h3>Conclusion</h3> Most of the general public accept the use of palliative sedation at the end of life, regardless of a potential life-shortening effect. However, confusion exists about what palliative sedation represents. This should be taken into account by healthcare professionals when communicating with patients and their relatives on end-of-life care options.
PHD2/3-dependent hydroxylation tunes cardiac response to β-adrenergic stress via phospholamban
Authors: Liang Xie, Xinchun Pi, W.H. Davin Townley-Tilson, Na Li, Xander H.T. Wehrens, Mark L. Entman, George E. Taffet, Ashutosh Mishra, Junmin Peng, Jonathan C. Schisler, Gerhard Meissner, Cam Patterson
Journal: Journal of Clinical Investigation (2015)

Ischemic heart disease is the leading cause of heart failure. Both clinical trials and experimental animal studies demonstrate that chronic hypoxia can induce contractile dysfunction even before substantial ventricular damage, implicating a direct role of oxygen in the regulation of cardiac contractile function. Prolyl hydroxylase domain (PHD) proteins are well recognized as oxygen sensors and mediate a wide variety of cellular events by hydroxylating a growing list of protein substrates. Both PHD2 and PHD3 are highly expressed in the heart, yet their functional roles in modulating contractile function remain incompletely understood. Here, we report that combined deletion of Phd2 and Phd3 dramatically decreased expression of phospholamban (PLN), resulted in sustained activation of calcium/calmodulin-activated kinase II (CaMKII), and sensitized mice to chronic β-adrenergic stress-induced myocardial injury. We have provided evidence that thyroid hormone receptor-α (TR-α), a transcriptional regulator of PLN, interacts with PHD2 and PHD3 and is hydroxylated at 2 proline residues. Inhibition of PHDs increased the interaction between TR-α and nuclear receptor corepressor 2 (NCOR2) and suppressed Pln transcription. Together, these observations provide mechanistic insight into how oxygen directly modulates cardiac contractility and suggest that cardiac function could be modulated therapeutically by tuning PHD enzymatic activity.
A Variant in PNPLA3 Associated With Fibrosis Progression but not Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection
Authors: Muhammad Ali, Adam Yopp, Purva Gopal, Muhammad S. Beg, Hao Zhu, William Lee, Amit G. Singal
Journal: Clinical Gastroenterology and Hepatology (2015)
Pathological grief and the activation of latent self-images
Authors: Mardi J. Horowitz, Nancy Wilner, Charles Marmar, Janice Krupnick
Journal: American Journal of Psychiatry (1980)

The authors studied the case material for patients treated with either psychoanalysis or brief therapy to examine the basis for the various states of pathological grief after berevavement. They view these states as intensifications or unusual prolongations of states found in normal grief and describe them in terms of the reemergence of self-images and role relationship models that had been held in check by the existence ofthe deceased person. This conclusion concerning preexisting mental schemata leads to an elaboration and partial revision of theories of regression, ambivalence, and introjection as causes of pathological grief.