tbuckley/cabot-search huggingface dataset:
Therapy-induced selective loss of leukemia-initiating activity in murine adult T cell leukemia
Authors: Hiba El Hajj, Marwan El-Sabban, Hideki Hasegawa, Ghazi Zaatari, Julien Ablain, Shahrazad T. Saab, Anne Janin, Rami Mahfouz, Rihab Nasr, Youmna Kfoury, Christophe Nicot, Olivier Hermine, William Hall, Hugues de Thé, Ali Bazarbachi
Journal: The Journal of Experimental Medicine (2010)

Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As2O3 and IFN-α combination, known to trigger Tax proteolysis, cures Tax-driven ATL in mice. Unexpectedly, this combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew in the primary hosts, only to ultimately abate later on. This loss of initial transplantability required proteasome function. A similar regimen recently yielded unprecedented disease control in human ATL. Our demonstration that this drug combination targeting Tax stability abrogates tumor cell immortality but not short-term growth may foretell a favorable long-term efficiency of this regimen in patients.
Reversible Connexin 43 Dephosphorylation During Hypoxia and Reoxygenation Is Linked to Cellular ATP Levels
Authors: Mark S. Turner, Guy A. Haywood, Peter Andreka, Lijing You, Patricia E. Martin, W. Howard Evans, Keith A. Webster, Nanette H. Bishopric
Journal: Circulation Research (2004)

Altered gap junction coupling of cardiac myocytes during ischemia may contribute to development of lethal arrhythmias. The phosphoprotein connexin 43 (Cx43) is the major constituent of gap junctions. Dephosphorylation of Cx43 and uncoupling of gap junctions occur during ischemia, but the significance of Cx43 phosphorylation in this setting is unknown. Here we show that Cx43 dephosphorylation in synchronously contracting myocytes during ischemia is reversible, independent of hypoxia, and closely associated with cellular ATP levels. Cx43 became profoundly dephosphorylated during hypoxia only when glucose supplies were limited and was completely rephosphorylated within 30 minutes of reoxygenation. Similarly, direct reduction of ATP by various combinations of metabolic inhibitors and by ouabain was closely paralleled by loss of phosphoCx43 and recovery of phosphoCx43 accompanied restoration of ATP. Dephosphorylation of Cx43 could not be attributed to hypoxia, acid pH or secreted metabolites, or to AMP-activated protein kinase; moreover, the process was selective for Cx43 because levels of phospho-extracellular signal regulated kinase (ERK)1/2 were increased throughout. Rephosphorylation of Cx43 was not dependent on new protein synthesis, or on activation of protein kinases A or G, ERK1/2, p38 mitogen-activated protein kinase, or Jun kinase; however, broad-spectrum protein kinase C inhibitors prevented Cx43 rephosphorylation while also sensitizing myocytes to reoxygenation-mediated cell death. We conclude that Cx43 is reversibly dephosphorylated and rephosphorylated during hypoxia and reoxygenation by a novel mechanism that is sensitive to nonlethal fluctuations in cellular ATP. The role of this regulated phosphorylation in the adaptation to ischemia remains to be determined.
Association of the<i>Taq</i>I A Polymorphism of the Dopamine D<sub>2</sub>Receptor Gene With Predisposition to Neuroleptic Malignant Syndrome
Authors: A Suzuki, T Kondo, K Otani, K Mihara, N Yasui-Furukori, A Sano, K Koshiro, S Kaneko
Journal: American Journal of Psychiatry (2001)

The pathophysiology of neuroleptic malignant syndrome is mainly explained by a central hypodopaminergic state. The familial occurrence of neuroleptic malignant syndrome suggests the involvement of a genetic mechanism in the predisposition to the syndrome. Therefore, the authors examined the association between the TaqI A polymorphism of the dopamine D(2) receptor gene (DRD(2)), which alters DRD(2) density and function, and the development of neuroleptic malignant syndrome.The subjects were 15 psychiatric patients who had developed neuroleptic malignant syndrome (12 patients with schizophrenia and three with major depression) and 138 patients with schizophrenia who had never developed neuroleptic malignant syndrome. The TaqI A genotypes, A1 and A2 alleles, were determined by the polymerase chain reaction method.The frequency of the A1 allele was significantly higher in the patients who had developed neuroleptic malignant syndrome (56.8%) than in the patients who had not (35.1%). The proportion of the A1 carrier was significantly higher in the patients with neuroleptic malignant syndrome (14 [93.3%] of 15 patients) than in those without the syndrome (79 [57.2%] of 138 patients).These findings suggest that the TaqI A DRD(2) polymorphism is associated with the predisposition to neuroleptic malignant syndrome.
Inhaled Leukotriene E<sub>4</sub>, But Not Leukotriene D<sub>4</sub>, Increased Airway Inflammatory Cells in Subjects with Atopic Asthma
Authors: GAIL M. GAUVREAU, KRISHNAN N. PARAMESWARAN, RICHARD M. WATSON, PAUL M. O'BYRNE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Allergen-induced late airway responses are associated with increased numbers of airway eosinophils and basophils. The purpose of this study was to compare and contrast the effects of inhaled cysteinyl leukotrienes LTD4 and LTE4, which are released during allergen- induced airway responses, and allergen, on airway inflammatory cells. Fifteen subjects with atopic, mild asthma inhaled diluent, LTD4, LTE4, and allergen. Spirometry was performed for 7 h, and sputum inflammatory cells were measured before, 7 h, and 24 h after challenges. The maximum early percent fall in FEV1 was 23.6 ± 1.4%, 21.6 ± 2.3%, 29.3 ± 2.4%, and 4.0 ± 1.1% after LTD4, LTE4, allergen, and diluent, respectively. Only inhaled LTE4 and allergen significantly increased sputum eosinophils at 7 h and 24 h, and sputum basophils at 7 h. Six additional subjects underwent airway biopsies 4 h after inhalation. There were significantly more eosinophils in the lamina propria after inhalation of LTE4 compared with LTD4 and diluent (p < 0.05). These results suggest cysteinyl leukotrienes play a role in eosinophil migration into the airways in allergic asthma, and for the same degree of bronchoconstriction, inhaled LTE4 causes more tissue and airway eosinophilia than LTD4.
Management of variceal haemorrhage in cirrhotic patients Reply
Authors: A K BURROUGHS
Journal: Gut (2001)

Editor,—We have serious concerns about several of the recent UK guidelines for the management of variceal haemorrhage in cirrhotic patients ( Gut 2000; 46 (suppl 3 and 4):iiiI–iii115), particularly those that contradict current published evidence. We highlight below the ones we feel are the most important.

In the management of acute variceal bleeding, variceal ligation is not the method of first choice which was given an AI recommendation. Meta-analysis of all trials of acute bleeding of banding versus injection sclerotherapy have shown no statistically significant difference between the two treatments for either control of bleeding or survival (data derived from 12 studies with 419 patients), with no statistical heterogeneity.1 

The implication of recommending ligation for acute bleeding is that double intubation would be necessary in a patient who is actively bleeding so as to attach the ligation device after the initial diagnostic endoscopy. Although there is no evidence, this would create more risk to the patient; it is common sense that a single intubation would be preferable and would take less time. At best the recommendation should be that either endoscopic technique could be used as first choice, dependent on operator expertise and facilities.

Secondly, there is evidence from randomised studies of vasoactive drug therapy combined with endoscopic techniques that combination therapy is superior in terms of control of bleeding. This is based on five randomised studies with 610 patients (pooled odds ratio 0.42, 95% confidence interval 0.29–0.6).1 Publication bias assessment has shown that 29 null or negative studies would be needed to render the results non-significant, and thus this effect is fairly robust. Moreover, in several of these studies vasoactive drugs were given before diagnostic endoscopy, demonstrating their utility during the period of resuscitation before endoscopy could be safely performed, which in practice may be several … 

Dr R Jalan, Institute of Hepatology, University College London Medical School, 69–75 Chenies Mews, London WC1E 6HX, UK. r.jalan{at}ucl.ac.uk 

Dr R Jalan, Institute of Hepatology, University College London Medical School, 69–75 Chenies Mews, London WC1E 6HX, UK. r.jalan{at}ucl.ac.uk
THE RATE OF DIVISION OF ANTIBODY-FORMING CELLS DURING THE EARLY PRIMARY IMMUNE RESPONSE
Authors: Donald A. Rowley, Frank W. Fitch, Donald E. Mosier, Susan Solliday, Lionel W. Coppleson, Barry W. Brown
Journal: The Journal of Experimental Medicine (1968)

Mitotic blocking agents, colchicine or Velban, were used to estimate cycle times of spleen cells which release hemolysin for sheep erythrocytes (plaque-forming cells). The cells were obtained either from rats immunized with sheep erythrocytes or from cultures of mouse spleen cells immunized in vitro with the same antigen. 2, 3, or 4 days after immunization, animals or cell cultures were treated with mitotic blocking agents for periods of time ranging from 2.5 to 7 hr; plaque-forming cells were then enumerated. Decreased numbers of plaque-forming cells were found after such treatment. The extent of reduction was a function of duration of the drug treatment and the method of immunization, but was independent of the time after immunization. The evidence presented is consistent with premises that: (a) plaque-forming cells in mitosis do not release sufficient antibody to be detected, (b) mitotic blocking agents, by arresting plaque-forming cells in metaphase, prevent not only detection of these cells but also the increase in number of plaque-forming cells which would have resulted from cell division, (c) mitotic blocking agents do not affect release of antibody by cells in interphase. Cell cycle times, based on the extent of reduction of plaque-forming cells per unit time of drug treatment, were estimated using a mathematical model appropriate for an exponentially increasing population of cells. Cell cycle times estimated using the mitotic blocking agents agreed well with cell doubling times calculated from the increase in plaque-forming cells occurring 1–4 days after immunization. Increased responses produced by higher antigen doses or treatment of immunized animals with an adjuvant resulted from an increased rate of division of responding cells and their progeny. The results are consistent with a cell selection theory of antibody formation. Antigenic stimulation causes relatively few cells to proliferate and to synthesize antibody; apparently the magnitude of the response is dependent primarily on the rate of division of responding cells. It is suggested on the basis of observations of in vitro-immunized cell cultures that the rate of division of responding cells may be dependent on the rate of interaction between two cell types, both of which are essential for the in vitro plaque-forming cell response.
5-Fu Plus Epirubicin is Superior to Standard 5-FU Plus Cisplatin and Epirubicin in the Neoadjuvant Gastric Cancer Spheroid Model
Authors: Ilmberger Christian, Joka Mareile, von hn-Rotfelser De Karin, Schirra Jörg, Werner Jens, Mayer Barbara
Journal: Annals of Oncology (2014)
Plasma Adiponectin and Leptin Levels, Body Composition, and Glucose Utilization in Adult Women With Wide Ranges of Age and Obesity
Authors: Alice S. Ryan, Dora M. Berman, Barbara J. Nicklas, Madhur Sinha, Ronald L. Gingerich, Grady S. Meneilly, Josephine M. Egan, Dariush Elahi
Journal: Diabetes Care (2003)

OBJECTIVE—The purpose of this study was to determine the relationships between plasma adiponectin and leptin levels, total and central obesity, and glucose utilization across the adult age span. RESEARCH DESIGN AND METHODS—We studied 148 women aged 18–81 years with a BMI range of 17.2–44.3 kg/m2. Total percent body fat was determined by dual-energy X-ray absorptiometry and abdominal fat by computed tomography. Glucose tolerance in non-type 2 diabetic volunteers was determined with an oral glucose tolerance test. Glucose utilization (M) was measured during the last 60 min of hyperinsulinemic-euglycemic clamps (240 pmol · m−2 · min−1). Plasma adiponectin levels were measured by radioimmunoassay. The women were separated into three age-groups: young, middle, and old (&amp;lt;40, 40–59, and ≥60 years, respectively), as well as by glucose tolerance status. RESULTS—Adiponectin concentrations did not differ by age-groups. There were significant age effects for BMI, percent body fat, visceral fat, subcutaneous abdominal fat, Vo2max, and M. Adiponectin levels were lower in the prediabetic women (n = 18) than in the normal glucose-tolerant women (n = 108) and the women with type 2 diabetes (n = 22) (both P &amp;lt; 0.05). Univariate correlations revealed significant negative relationships between plasma adiponectin levels and BMI, percent body fat, visceral fat, subcutaneous abdominal fat, fasting leptin, and fasting insulin and positive relationship with M (all P &amp;lt; 0.05). In a multiple stepwise regression model to predict adiponectin, only M remained in the model at P &amp;lt; 0.001. Multivariate analyses revealed a significant relation for M as a function of adiponectin, insulin, and Vo2max. CONCLUSIONS—The data suggest that plasma adiponectin does not change with age but levels are negatively associated with percent body fat, visceral fat, subcutaneous abdominal fat, insulin, and leptin levels in women. Adiponectin is positively associated with M across the age span in women.
Transient Increase in Intraocular Pressure during a Dose-Tapering Regime of Systemic Dexamethasone in Preterm Infants
Authors: Pak C. Ng, Cheuk H. Lee, Barbara S.M. Tam, Samuel P.S. Wong, Hugh S. Lam, Alvin K.H. Kwok, Tai F. Fok
Journal: Ophthalmology (2008)
Disease-modifying effects of TD-198946 on progressed osteoarthritis in a mouse model
Authors: Fumiko Yano, Shinsuke Ohba, Yoko Hosaka, Taku Saito, Ung-il Chung
Journal: Annals of the Rheumatic Diseases (2014)

We previously reported that a thienoindazole derivative TD-198946 (TD) induced chondrogenic differentiation in vitro without promoting hypertrophy, and prevented and repaired the degeneration of articular cartilage observed in a surgically induced mouse model of osteoarthritis (OA).1 In that study, the TD injections into mouse knee joints began on the day of the OA surgery (prevention model) or 4 weeks after the surgery (repair model), and continued periodically until 8 weeks after the surgery.1 

Here we report the disease-modifying effects of TD injections on progressed OA in mice. We examined 4-week and 8-week injection protocols that began 8 weeks after the OA surgery (figure 1A). Eight mice in each group (n=8) were then subjected to histopathological assessments of knee joint OA. The severity of OA was quantified using the Osteoarthritis Research Society International histopathology scoring system (scale: 0–6)2 on histological sections stained with Safranin O/fast green. The OA surgery, preparation of TD, injection of TD into mouse knee joints and preparation of paraffin sections were performed as …
Effect of medroxyprogesterone on arterial blood gases, leptin and neuropeptide Y in postmenopausal females
Authors: T. Saaresranta, K. Irjala, O. Polo
Journal: European Respiratory Journal (2002)

The right temporal lobe variant of frontotemporal dementia (FTD) is an uncommon progressive neurodegenerative disorder. We present the case of a 77-year-old right-handed man who presented with altered behaviour and problems with interpersonal relationships. He had no decline in cognitive function but brain perfusion single-photon emission CT demonstrated distinct hypoperfusion in the right temporal pole. At 2-year follow-up, he could not recognise his wife’s relatives; and at 3-year follow-up, he had semantic aphasia. Decreased brain perfusion extended from the right temporal lobe into the contralateral temporal and both frontal lobes. These findings suggest that the right temporal lobe variant of FTD should be considered in elderly patients with altered behaviour and problems with interpersonal relationships, even if dementia is not suspected. The right anterior temporal lobe may play a key role in the onset of the early symptoms of this disease.
Regulation of Proopiomelanocortin Gene Expression in Pituitary
Authors: JAMES R. LUNDBLAD, JAMES L. ROBERTS
Journal: Endocrine Reviews (1988)

THE POMC gene encodes the complex precursor to a variety of biologically active, important neuromodulator and endocrine peptides. It is expressed in a variety of tissues in the mammal, but its main site of expression is the pituitary anterior lobe cortocotroph and intermediate lobe melanotroph. The POMC molecule is posttranslationally processed to different biologically active peptides in these two cell types, with ACTH, β-lipotropin, and β-endorphin being major products in the corticotroph and α-MSH, corticotropin-like intermediate lobe peptide, and acetyl-β-endorphin in the melanotroph (1). This array of different biological activities derived from the POMC molecule possibly necessitates the observed complex regulation of POMC peptide secretion and POMC gene expression in pituitary. Regulation of POMC peptide secretion has recently been reviewed in several places (2, 3). This review will deal primarily with the regulation of POMC gene expression in rat and mouse pituitary tissues, the species in which the majority of the work has been done although examples of other mammalian systems will be used where appropriate.
Metformin, but Not Rosiglitazone, Attenuates the Increasing Plasma Levels of a New Cardiovascular Marker, Fibulin-1, in Patients With Type 2 Diabetes
Authors: Vibe Skov, Claudia Cangemi, Jeppe Gram, Mette M. Christensen, Ellen Grodum, Ditte Sørensen, W. Scott Argraves, Jan E. Henriksen, Lars M. Rasmussen
Journal: Diabetes Care (2013)

OBJECTIVE The extracellular matrix protein fibulin-1 is upregulated in the arterial wall in type 2 diabetes (T2D) and circulates in increased concentrations in diabetes. Metformin is an antidiabetic drug with beneficial cardiovascular disease effects in diabetes. We hypothesized that metformin would influence the increased level of plasma fibulin-1 in diabetes. RESEARCH DESIGN AND METHODS After a 4-week run-in period, 371 eligible patients with T2D were randomized to treatment groups in a factorial design including insulin alone (control), +metformin, +rosiglitazone, or +both metformin and rosiglitazone. Plasma fibulin-1 was analyzed at the beginning of the study and after 18 and 24 months. RESULTS Plasma fibulin-1 increased in all groups throughout the 2-year period; however, the increase was strongly attenuated among patients treated with metformin. A highly significant difference was observed when the mean change in plasma fibulin-1 was compared between metformin- and non–metformin-treated individuals both at 18 and 24 months of treatment, but rosiglitazone had no effect. Metformin and rosiglitazone alone reduced the HbA1c levels to comparable levels and in combination even further. CONCLUSIONS Metformin attenuates the increase in plasma fibulin-1 concentrations in T2D, independently of glycemic effects. Changes in fibulin-1 may reflect an important element in diabetic arteriopathy that can be influenced by metformin.
Role and contribution of viral respiratory infections to asthma
Authors: William W. Busse
Journal: Allergy (1993)

Summary From the above observations, it is apparent that many respiratory viruses causes a change in airway function such that bronchial obstruction is more likely to occur in patients with asthma. Furthermore, there is also evidence that viruses act through a number of pathways to enhance the likelihood of an inflammatory response. Subsequent observations must focus on the ability of viruses to stimulate cytokine production, which could then upregulate the allergic airway inflammatory response. With the unfolding of such observations, it is highly likely that greater insights into this major provoking factor in asthma will become more apparent as well as clearer insight into mechanisms of asthma.
A randomised, controlled study on the effects of a short-term endurance training programme in patients with major depression * Commentary
Authors: K Knubben, F M Reischies, M Adli, P Schlattmann, M Bauer, F Dimeo, L Ansley
Journal: British Journal of Sports Medicine (2006)

<b>Objective:</b> To evaluate the short-term effects of exercise in patients with major depression. <b>Design:</b> Prospective, randomised, controlled study. <b>Setting:</b> A university hospital. <b>Patients:</b> A consecutive series of 38 inpatients with a major depression episode undergoing standard clinical antidepressant drug treatment. <b>Interventions:</b> Patients were randomly assigned to an exercise (walking, n = 20) or placebo (low-intensity stretching and relaxation exercises, n = 18) group. Training was carried out for 10 days. <b>Main outcome measurements:</b> Severity of depression assessed with the Bech-Rafaelsen Melancholy Scale (BRMS) and the Center for Epidemiologic Studies Depression scale (CES-D). <b>Results:</b> After 10 days, reduction of depression scores in the exercise group was significantly larger than in the placebo group (BRMS: 36% <i>v</i> 18%; CES-D: 41% <i>v</i> 21%; p for both = 0.01); the proportion of patients with a clinical response (reduction in the BRMS scores by more than six points) was also larger for the exercise group (65% <i>v</i> 22%, p&lt;0.01). <b>Conclusions:</b> Endurance exercise may help to achieve substantial improvement in the mood of selected patients with major depression in a short time.
Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor.
Authors: I Ferrari, M J Levin, G Wallukat, R Elies, D Lebesgue, P Chiale, M Elizari, M Rosenbaum, J Hoebeke
Journal: The Journal of Experimental Medicine (1995)

Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.