tbuckley/cabot-search huggingface dataset:
Keratin expression in basal cell carcinomas
Authors: A.C. MARKEY, E.BIRGITTE LANE, D.M. MACDONALD, IRENE M. LEIGH
Journal: British Journal of Dermatology (1992)

The keratin phenotype of 15 cases of basal cell carcinoma was assayed immunohistochemically using a panel of monospecific antibodies to single keratin polypeptides. Whilst tumour tissue strongly expressed primary keratins 5 and 14 (normally synthesized in basal keratinocytes) no expression of secondary keratins 1 and 10 (characteristic of skin-type differentiation) was detected. Keratin 17, characteristic of the outer hair root sheath, was strongly expressed in all tumours. Keratin 19 was also normally expressed in parts of the hair follicle and was detected in four cases. The ‘high cell turnover’ keratin 16 was frequently induced in the overlying epidermis, but was rare within tumour tissue. No expression of simple epithelial keratins 8 and 18 was detected. Whilst the keratin phenotype of tumour cells is similar to that of basal cells within part of the hair root sheath, in keeping with suggestions of a follicular origin for basal cell carcinomas, the findings are also compatible with an origin from interfollicular pluripotent stem cells differentiating towards follicular structures.
PTU-109 Azathioprine In The Elderly – Is It Tolerated And Is It Safe?
Authors: S Dharmasiri, H Johnson, S McLaughlin, S Weaver
Journal: Gut (2014)

<h3>Introduction</h3> The use of Azathioprine (AZA) for maintenance of remission in Inflammatory Bowel Disease (IBD) is common practice as part of national and international guidelines. Side effects however are common. Of 353 consecutive patients commencing AZA in our organisation, 36% were not taking it at one year. With an ageing population, IBD is increasingly relevant in those over 75 years old. However there is little data concerning the efficacy and tolerability of AZA in this age group. <h3>Methods</h3> We maintain a prospective database of IBD patients. All patients commenced on AZA between June 2005 and October 2012 over the age of 75 were identified. Thiopurine Methyl Transferase (TPMT) levels were checked in all patients and AZA was prescribed at 2–2.5 mg/kg, with 50% dose reduction in those with low TPMT. We monitor full blood count and LFTs weekly for 8 weeks after commencing therapy. <h3>Results</h3> 25 patients were identified, (7 CD, 18 UC). The mean age at which AZA was started was 78 (range 75–86), 16 were male (64%). All patients were followed up for at least one year. 12 (48%) were intolerant of AZA. Reasons for stopping AZA were; hepatitis, 2 (8%); vomiting, 5 (10%); pancreatitis, 1 (4%); myelosupression (1); joint pain (1); infection (1); and general malaise (1). The mean duration of AZA use in these patients was 34 days (Range 3–89). 13 (52%) tolerated the drug well with one of this group having the drug actively withdrawn at 701 days in complete clinical, endoscopic and histological remission. There were four deaths (16%). Two died in the group intolerant of AZA (84 year old died of stroke 888 days after 13 days of AZA; 82 year old died in the community 140 days after 5 days of AZA). Two people died in the AZA treated group (83 year old died in the community on day 1476 of AZA; 79 year old died following cardiac arrest on day 212 of AZA). <h3>Conclusion</h3> Our data demonstrate that AZA is an effective treatment in the elderly. It appears to be less well tolerated than in the general population with 48% intolerant of the drug within 3 months. Within the limitations of this study it appears to be safe. The increased incidence of drug intolerance in this population group may suggest that low-dose azathioprine and allopurinol co-therapy should be considered first-line therapy in this group. A further study to clarify this is required. <h3>Disclosure of Interest</h3> S. Dharmasiri Conflict with: Funding from Warner Chicott to attend ECCO congress 2014, H. Johnson Conflict with: Guest at Falk symposium, Barcelona and London 2013, S. McLaughlin Conflict with: sponsorship from Falk to attend Ecco 2013 and falk symposia in London and Barcelona. Attendance at local evening ibd dinner meetings sponsored by falk and Abbvie, S. Weaver: None Declared.
Inhomogeneity of Lung Parenchyma during the Open Lung Strategy
Authors: Salvatore Grasso, Tania Stripoli, Marianna Sacchi, Paolo Trerotoli, Francesco Staffieri, Delia Franchini, Valentina De Monte, Valerio Valentini, Paolo Pugliese, Antonio Crovace, Bernd Driessen, Tommaso Fiore
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: The open lung strategy aims at reopening (recruitment) of nonaerated lung areas in patients with acute respiratory distress syndrome, avoiding tidal alveolar hyperinflation in the limited area of normally aerated tissue (baby lung).Objectives: We tested the hypothesis that recruited lung areas do not resume elastic properties of adjacent baby lung.Methods: Twenty-five anesthetized, mechanically ventilated pigs were studied. Four lung-healthy pigs served as controls and the remaining 21 were divided into three groups (n = 7 each) in which lung injury was produced by surfactant lavage, lipopolysaccharide infusion, or hydrochloride inhalation. Computed tomography scans, respiratory mechanics, and gas exchange parameters were recorded under three conditions: at baseline, during lung recruitment maneuver, and at end-expiration and end-inspiration when ventilating after an open lung protocol.Measurements and Main Results: During recruitment maneuver and open lung protocol, the gas volume entering the insufficiently aerated compartment was 96% (75–117%) and 48% (41–63%) (median [interquartile range]) of the functional residual capacity measured before and at zero end-expiratory pressure, respectively. Nonetheless, the volume of hyperinflated lung increased during both recruitment maneuver (by 1–28% of total lung volume; P < 0.01) and open lung protocol ventilation at end-inspiration (by 1–15% of total lung volume; P < 0.01). Regional elastance of recruited lung tissue was consistently higher than that of the baby lung regardless of the ARDS model (P < 0.01).Conclusions: Alveolar recruitment is not protective against hyperinflation of the baby lung because lung parenchyma is inhomogeneous during ventilation with the open lung strategy.
NBCn1 (slc4a7) Mediates the Na <sup>+</sup> -Dependent Bicarbonate Transport Important for Regulation of Intracellular pH in Mouse Vascular Smooth Muscle Cells
Authors: Ebbe Boedtkjer, Jeppe Praetorius, Christian Aalkjaer
Journal: Circulation Research (2006)

The contribution of sodium-dependent bicarbonate transport to intracellular pH (pH(i)) regulation in vascular smooth muscle cells is controversial, partly because the molecular identity of the transporter(s) responsible has not been identified. Here, using the pH-sensitive fluorophore 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), we show that smooth muscle cells of intact mouse mesenteric, coronary, and cerebral small arteries all display a sodium- and bicarbonate-dependent pH(i) recovery after an NH4+-prepulse. The sodium-dependent bicarbonate flux was largely 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) sensitive (56% to 91%) and of a magnitude similar to the amiloride-sensitive flux. Additionally, steady-state pH(i) was lower (0.2 to 0.4 pH units magnitude) in all 3 vascular beds when CO2/bicarbonate was omitted. RT-PCR analyses showed that NBCn1 (slc4a7) is the only Na+-dependent bicarbonate transporter of the slc4 family detectable at the mRNA level in all 3 vascular beds investigated. Whole-mount immunolabeling and immunogold electron microscopy confirmed the presence of NBCn1 protein in the sarcolemma of mouse mesenteric small arterial smooth muscle cells. Intact mouse mesenteric small arteries were electropermeated to facilitate transfection with small interfering RNA targeting NBCn1, which resulted in an approximate 43% decrease in the ratio of NBCn1 to glyceraldehyde-3-phosphate dehydrogenase mRNA. After knock-down, we found a decreased steady-state pH(i) (0.21+/-0.08 pH units) as well as a 68+/-10% decrease in the net Na+-dependent, amiloride-insensitive base influx after acid load. Finally, omission of CO2/bicarbonate resulted in a decreased contractile response to norepinephrine after sustained exposure to the agonist, underlining the importance of CO2/bicarbonate for vascular contractility. We conclude that NBCn1 mediates the Na+-dependent bicarbonate transport important for pH(i) regulation in smooth muscle cells of mouse mesenteric, coronary, and cerebral small arteries.
Antitumor Activity of Gefitinib in Malignant Rhabdoid Tumor Cells <b> <i>In vitro</i> </b> and <b> <i>In vivo</i> </b>
Authors: Yasumichi Kuwahara, Hajime Hosoi, Shinya Osone, Masakazu Kita, Tomoko Iehara, Hiroshi Kuroda, Tohru Sugimoto
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of young children. Current treatments have had only limited success. Epidermal growth factor receptor (EGFR) was found recently to be expressed on MRT cell lines. Gefitinib (trade name Iressa) is an oral and selective EGFR-tyrosine kinase inhibitor and has been demonstrated to be effective in inhibiting the proliferation of cancer cells in vivo as well as in clinical trials. This encouraged us to examine the antitumor effects of gefitinib on MRT cells in vitro and in vivo. Experimental Design: The expression of EGFR in two MRT tumors and two MRT cell lines (MP-MRT-AN and KP-MRT-NS), established from these two tumor tissues, was examined by immunohistochemistry, immunofluorescence, and immunoblot. The effect of gefitinib on EGFR phosphorylation was examined by immunoblot. The effects of gefitinib on cell growth and apoptosis were examined by cell growth assay and terminal deoxynucleotidyl transferase-mediated nick end labeling assay. The in vivo effect of gefitinib was assessed in athymic mice that had been xenografted with MRT cells. Results: The expression of EGFR was detected in both tumor tissues and cell lines. Gefitinib inhibited EGFR-phosphorylation (IC50 &amp;lt; 0.1 μmol/L) and in vitro cell growth (IC50 = approximately 10–12 μmol/L), and a high concentration of gefitinib (20 μmol/L) induced apoptosis in vitro (MP-MRT-AN, 42.9% and KP-MRT-NS, 47.2%). Furthermore, gefitinib at 150 mg/kg had a cytostatic effect on established MRT xenografts (MP-MRT-AN, P = 0.039 and 0.0014; and KP-MRT-NS, P = 0.048 and 0.0086). Conclusions: Our results demonstrate that gefitinib has antitumor effects in MRT cells in vitro and in vivo and, thus, has promise as a novel and therapeutic strategy for MRT.
Child and Adolescent Obesity: Causes and Consequences, Prevention and Management
Authors: Helen P Roper
Journal: Journal of the Royal Society of Medicine (2003)

We are bombarded with warnings and descriptions of burgeoning obesity in the medical and lay press. We all know the apparent paradoxes—that we are eating fewer calories and even a smaller proportion of fat in our diet than 25 years ago, yet we are getting fatter. Is sloth rather than greed really the answer?
Randomized Placebo-Controlled Study of Low-Dose Warfarin for the Prevention of Central Venous Catheter–Associated Thrombosis in Patients With Cancer
Authors: Stephen Couban, Michael Goodyear, Margot Burnell, Sean Dolan, Parveen Wasi, David Barnes, Darlene MacLeod, Erica Burton, Pantelis Andreou, David R. Anderson
Journal: Journal of Clinical Oncology (2005)

In this multicenter, randomized, placebo-controlled clinical trial, we studied whether warfarin 1 mg daily reduces the incidence of symptomatic central venous catheter (CVC) -associated thrombosis in patients with cancer.Two hundred fifty-five patients with cancer who required a CVC for at least 7 days were randomly assigned to receive warfarin 1 mg or placebo.There were 11 (4.3%) symptomatic CVC-associated thromboses among 255 patients, with no difference in the incidence of symptomatic CVC-associated thrombosis between patients taking warfarin 1 mg daily (six of 130 patients; 4.6%) and patients taking placebo (five of 125 patients; 4.0%; hazard ratio, 1.20; 95% CI, 0.37 to 3.94). Warfarin had no effect on CVC life span (84 days v 63 days in control and warfarin groups, respectively; 95% confidence limit, -16 to 55 days; P = .09), and it did not affect the number of premature CVC removals (23.2% v 25.4% in control and warfarin groups, respectively; 95% confidence limit of difference -8.34 to 12.71; P = .68) or the frequency of major bleeding episodes (2% v 0% in control and warfarin groups, respectively; P = .5, Fisher's exact test).Symptomatic CVC-associated thrombosis in patients with cancer, although significant, is less common than previously reported. In this study, the administration of warfarin 1 mg daily did not reduce the incidence of symptomatic CVC-associated thrombosis in patients with cancer. However, the low rate of symptomatic CVC-associated thrombosis means that a much larger trial is required to address this issue definitively.
Thyroid Disease and the Heart
Authors: Irwin Klein, Sara Danzi
Journal: Circulation (2007)

The cardiovascular signs and symptoms of thyroid disease are some of the most profound and clinically relevant findings that accompany both hyperthyroidism and hypothyroidism. On the basis of the understanding of the cellular mechanisms of thyroid hormone action on the heart and cardiovascular system, it is possible to explain the changes in cardiac output, cardiac contractility, blood pressure, vascular resistance, and rhythm disturbances that result from thyroid dysfunction. The importance of the recognition of the effects of thyroid disease on the heart also derives from the observation that restoration of normal thyroid function most often reverses the abnormal cardiovascular hemodynamics. In the present review, we discuss the appropriate thyroid function tests to establish a suspected diagnosis as well as the treatment modalities necessary to restore patients to a euthyroid state. We also review the alterations in thyroid hormone metabolism that accompany chronic congestive heart failure and the approach to the management of patients with amiodarone-induced alterations in thyroid function tests.
Effects of endothelin on the coronary vascular bed in open-chest dogs.
Authors: J P Clozel, M Clozel
Journal: Circulation Research (1989)

The goal of the present study was to evaluate the effects of endothelin, a newly discovered very potent vasoconstrictor secreted by endothelial cells, on the coronary vascular bed. For this purpose, the effects of endothelin injected intracoronarily were tested in open-chest anesthetized dogs with the circumflex coronary artery cannulated and perfused at a constant pressure of 100 mm Hg. Circumflex blood flow, transmural distribution of coronary blood flow (radioactive microspheres), circumflex coronary artery diameter (piezoelectric crystals), and circumflex luminal surface area were measured. Endothelin decreased coronary blood flow by 30% and 61% with doses of 1 and 3 micrograms, respectively. A dose of 10 micrograms was lethal. The decrease of coronary blood flow was larger in the subepicardium than in the subendocardium, which explains that the endocardial-epicardial blood flow ratio increased from 1.27 +/- 0.05 to 1.98 +/- 0.23 (p less than 0.001) with a dose of 3 micrograms endothelin. Circumflex surface area decreased by 7% (p = NS) and 20% (p less than 0.01) with doses of 1 and 3 micrograms endothelin, respectively. The action of endothelin was not modified by the concomitant alpha-adrenergic blockade, serotonergic blockade, angiotensin converting enzyme inhibition, or cyclooxygenase inhibition. We conclude that endothelin is a potent coronary vasoconstrictor with a selective effect on the subepicardium. At least part of the increase of coronary vascular resistance is due to a constriction of the large coronary arteries. Further studies are required to determine the physiopathological role of endothelin, especially in coronary vasospasm.
ROBO2 Gene Variants Are Associated with Familial Vesicoureteral Reflux
Authors: Aida M. Bertoli-Avella, Maria Luisa Conte, Francesca Punzo, Bianca M. de Graaf, Giuliana Lama, Angela La Manna, Cesare Polito, Carolina Grassia, Bruno Nobili, Pier Francesco Rambaldi, Ben A. Oostra, Silverio Perrotta
Journal: Journal of the American Society of Nephrology (2008)

The SLIT2 receptor ROBO2 plays a key role in the formation of the ureteric bud, and its inactivation in mice leads to supernumerary ureteric bud development, lack of ureter remodeling, and improper insertion of the ureters into the bladder. Recently, two heterozygous ROBO2 missense mutations were identified in two families with primary vesicoureteral reflux occurring in combination with congenital anomalies of the kidney and urinary tract (VUR/CAKUT). This study investigated a possible causal role of ROBO2 gene variants in 95 unrelated patients with primary VUR (n = 78) or VUR/CAKUT. Eighty-two percent of all patients had a family history of genitourinary anomalies. Twenty-four ROBO2 gene variants were identified by direct sequencing of all 26 exons and the exon-intron boundaries. Of these, four led to amino acid substitutions: Gly328Ser, Asn515Ile, Asp766Gly, and Arg797Gln. When the families were examined, the missense variants co-segregated with VUR (three families) or VUR/CAKUT (one family). These variants were not found in 190 control subjects, and the affected amino acids have been conserved through evolution. In conclusion, a relatively high frequency of ROBO2 variants (5.1%) was found in familial cases; however, functional studies and validation in other cohorts are warranted.
First case of paralytic intestinal ileus after double balloon enteroscopy
Authors: A Attar
Journal: Gut (2005)

Pitfalls in diagnosing acute pancreatitisWe thank Jolobe for his letter (Gut 2005;54:1207-8) which mentions the difficulty of establishing the diagnosis of acute pancreatitis in patients with diabetic ketoacidosis.We did not address diagnostic tests and medical intensive care treatment of acute pancreatitis in our article, 1 but reviewed the interventional and surgical treatment strategies in acute pancreatitis.There is no doubt that treatment of acute pancreatitis, including organ failure in its early phase, is solely supportive. 2 Due to improvements in inten- sive care medicine, mortality of severe disease has decreased dramatically over the past decades.However, to treat patient adequately, the correct diagnosis has to be made.Therefore, the first step in the diagnostic process of acute pancreatitis is to think of this disease.According to the latest classification from Atlanta, 3 acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems.From a clinical point of view, acute upper abdominal pain and elevated pancreatic enzyme levels are needed to diagnose acute pancreatitis.As pointed out by Jolobe in his letter, acute pancreatitis is still underdiagnosed under certain clinical conditions, including diabetic ketoacidosis, but also in other clinical situations, such as shock of unknown origin, patients under intensive care treatment, as well as rare causes of the disease.As acute pancreatitis can be associated with diabetic ketoacidosis and the association between these two is a two way cause-and-effect relationship, early imaging of the pancreas is recommended in these patients to establish the correct diagnosis.Our article focused on the surgical and interventional treatment of severe acute pancreatitis.
Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen
Authors: J Muller-Quernheim, K Kienast, M Held, S Pfeifer, U Costabel
Journal: European Respiratory Journal (1999)

In a few patients with chronic sarcoidosis, prolonged, unacceptably high doses of corticosteroids are required to achieve symptomatic relief. In these cases, a corticosteroid-sparing drug might be administered to allow long-term treatment without the adverse effects of corticosteroids. This study examines azathioprine as a prednisolone-sparing treatment. In an open study, the course of 11 patients with chronic sarcoidosis was analysed. In an induction phase, 2 mg azathioprine x kg body weight (BW)(-1) x day(-1) in combination with 0.6-0.8 mg prednisolone x kg BW(-1) x day(-1) were administered with prednisolone being reduced to 0.1 mg x kg BW(-1) x day(-1) within 2-3 months. This was followed by a 21-22-month maintenance phase with 2 mg azathioprine x kg BW(-1) x day(-1) and 0.1 mg prednisolone x kg BW(-1) day(-1). Clinical parameters and immunological findings of bronchoalveolar lavage (BAL) were analysed. All patients had significant symptomatic relief and improvements or resolutions of physiological, serological and radiographic findings without suffering from serious adverse effects. Nine of 11 patients completed therapy after 19-26 months, and 2/11 patients terminated therapy after 8 and 12 months, respectively. Eight patients had remissions lasting 4-73 months. Three relapses occurred after 8, 18, and 22 months. During the induction phase, BAL cell composition changed and their activity in terms of cytokine release was suppressed. This preliminary study suggests that azathioprine may be effective as a corticosteroid-sparing agent in long-term therapy of sarcoidosis, but a much larger study is necessary to give the definitive answer.
Embodied representations are part of a grouping of representations
Authors: Christopher Habel, Barbara Kaup, Stephanie Kelter
Journal: Behavioral and Brain Sciences (1997)

Glenberg argues for embodied representations relevant to action. In contrast, we propose a grouping of representations, not necessarily all being directly embodied. Without assuming the existence of representations that are not directly embodied, one cannot account for the use of knowledge abstracted from direct experience.
Inhibitory action of a met-enkephalin on ACTH release in man.
Authors: E del Pozo, J Martin-Perez, A Stadelmann, J Girard, J Brownell
Journal: Journal of Clinical Investigation (1980)

In order to study the mechanism of action of a Met-enkephalin (FK 33824) on the pituitary-adrenal axis eight normal male volunteers were subjected to an ACTH stimulation test. Lysine-vasopressing (LVP), 5 IU, was injected intramuscularly after pretreatment with 0.5 mg FK 33824 i.m. or a placebo. In six of the subjects the opiate was again administered preceding a single injection of 0.25 mg ACTH beta 1-24 i.m. Blood was collected at regular intervals and ACTH and cortisol concentrations analyzed in all samples. LVP induced significant plasma ACTH (P < 0.05) and cortisol (P < 0.001) increases. Pretreatment with FK 33824 completely antagonized the effect of LVP. Furthermore, the cortisol elevation after exogenous ACTH was not modified by previous administration of FK 33824. It is concluded that the Met-enkephalin derivative FK 33824 directly suppresses ACTH release from the pituitary without influencing adrenal synthesis of cortisol.