tbuckley/cabot-search huggingface dataset:
Cytokine-independent repression of rodentNtcp in obstructive cholestasis
Authors: Andreas Geier, Gernot Zollner, Christoph G. Dietrich, Martin Wagner, Peter Fickert, Helmut Denk, Nico van Rooijen, Siegfried Matern, Carsten Gartung, Michael Trauner
Journal: Hepatology (2005)

Cholestatic liver injury is associated not only with accumulation of bile acids but also with activation of proinflammatory cytokines. Common bile duct ligation (CBDL) induces sustained downregulation of the Na(+)/taurocholate cotransporter (Ntcp) in rodent liver. Although repression of Ntcp during endotoxemia is cytokine mediated, it is unclear whether inflammatory cytokines contribute to this downregulation in obstructive cholestasis. Cytokine inactivation in CBDL rats and mice was either performed directly with tumor necrosis factor alpha (etanercept) or interleukin 1 beta inactivation (anakinra/AMG 719) or indirectly Kupffer cell depletion via intraperitoneal administration of liposome-encapsulated dichloromethylene bisphosphonate. Protein and messenger RNA (mRNA) expression of Ntcp and short heterodimer partner (SHP) were analyzed via Western and Northern blotting. Key regulators of Ntcp (hepatocyte nuclear factor 1 alpha [HNF-1alpha], HNF-4alpha, retinoid X receptor alpha [RXRalpha]:retinoic acid receptor alpha [RARalpha]) were studied via electrophoretic mobility shift analysis and nuclear Western blot analysis. Both methods of cytokine inactivation failed to maintain Ntcp protein or mRNA expression within 3 days after CBDL in either rats or mice (20%-40% of sham controls), while SHP mRNA expression increased three- to five-fold. Decreased nuclear HNF-1alpha and HNF-4alpha protein levels (45% and 60% of sham controls, respectively) and HNF-1alpha binding activity (32% of sham controls) were not restored during cytokine inactivation after CBDL, indicating cytokine-independent mechanisms of Ntcp regulation. RXRalpha:RARalpha binding remained unchanged in all experimental conditions. In conclusion, during obstructive cholestasis accumulating bile acids per se, without major contribution of cytokines, leads to downregulation of Ntcp via repression of HNF-1alpha and HNF-4alpha.
Use of radiofrequency current to ablate accessory connections in children.
Authors: M Dick, B K O'Connor, G A Serwer, S LeRoy, B Armstrong
Journal: Circulation (1991)

BACKGROUND Several investigators have recently ablated electrophysiologically mapped accessory connections in the adult human myocardium by using radiofrequency current. To examine the effectiveness and safety of radiofrequency current for ablation of accessory connections in children, 20 consecutive patients (age, 3-18 years) with preexcitation and/or supraventricular tachycardia were evaluated by electrophysiological study. METHODS AND RESULTS Nineteen of the 20 patients were completely studied and demonstrated accessory connections. After identification of the earliest retrograde atrial activation site, a steerable 7F catheter (with a 4-mm-long electrode at the distal tip) was placed within the ventricular cavity ipsilateral to the accessory connection and positioned at the atrioventricular valve annulus directly opposite the earliest point of retrograde atrial activation. Radiofrequency current was delivered at 50-65 volts for 10-60 seconds at a frequency of 500 kHz. Radiofrequency pulses were delivered for two to 26 trials. Upon completion of radiofrequency trials, repeat electrophysiological testing was performed. Thirteen of 19 subjects (68%) experienced definite successful ablation of their accessory pathway; an additional patient had probable successful ablation, yielding an overall success rate of 74%. Eighty-seven percent of individuals with a left-sided pathway had permanent ablation and 100% with a manifest left-sided pathway experienced successful ablation. Only 29% of the first seven patients had a successful result; in contrast, 92% of the next 12 patients had successful interruption of their accessory pathways. After ablation, 4-day continuous electrocardiographic telemetry disclosed no significant arrhythmias. CPK enzyme rises peaked at 12-24 hours. The rise was excessive and associated with general anesthesia in five patients. The isoenzyme MB fraction rose mildly in five other patients and returned to normal within 72 hours. No clinical or electrocardiographic evidence of myocardial ischemia was detected. Follow-up for 4-12 months indicates no return of preexcitation or tachycardia in any patient whose accessory connection was successfully ablated. CONCLUSIONS This experience indicates that radiofrequency current is an effective and safe technique for ablation of accessory connections in children.
Partial HLA matching and RH incompatibility resulting in graft versus host reaction and Evans syndrome after liver transplantation
Authors: Celia Grosskreutz, Oksana Gudzowaty, Patricia Shi, Gonzalo Rodriguez‐Laiz, Adriana Malone, Luis Isola
Journal: American Journal of Hematology (2008)

Abstract We report a case of a 67‐year‐old male who underwent OLT from a deceased, sex‐matched donor. Two months later he developed Evans syndrome and GVHD of the skin. Donor and recipient were matched for HLA‐A and ‐B loci in the direction of rejection but mismatched in the direction of GVHD and fully mismatched for DRB1. These mismatches were permissible for engraftment of donor T‐cells but led to GVHD. Chimerism appeared restricted to the T‐cell compartment. In this case, partially matched passenger lymphocytes triggered a graft versus host reaction. In addition, alloantibodies caused cytopenias that improved after immunosuppression. HLA typing was critical in confirming this rare diagnosis and elucidating its cause. Recipients of solid organs from donors that are partially matched in the direction of rejection may need to be closely monitored for GVHD. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Learning Theories and Supportive Psychotherapy
Authors: PHILIP R. SULLIVAN
Journal: American Journal of Psychiatry (1971)

Supportive therapy is the Cinderella of psychotherapies. Considered a simple-minded endeavor, it seldom evokes theoretical conceptualizations, and the neophyte psychiatrist is usually left to develop his own techniques intuitively. The author points out the usefulness of learning principles in clarifying some common elements in supportive psychotherapy: 1) expressions of interest and solicitude, 2) giving advice, and 3) ventilation.
Treatment for chronic myelogenous leukemia: the long road to imatinib
Authors: Tony Hunter
Journal: Journal of Clinical Investigation (2007)

The scientists of today have become accustomed to the extremely rapid pace of progress in the biomedical sciences spurred on by the discovery of recombinant DNA and the advent of automated DNA sequencing and PCR, with progress usually being measured in months or years at most. What is often forgotten, however, are the many prior advances that were needed to reach our present state of knowledge. Here I illustrate this by discussing the scientific discoveries made over the course of the past century and a half that ultimately led to the recent successful development of drugs, particularly imatinib mesylate, to treat chronic myelogenous leukemia.
Use of Inert Gases to Study the Interaction of Blood Flow and Diffusion during Passive Absorption from the Gastrointestinal Tract of the Rat
Authors: Michael D. Levitt, David G. Levitt
Journal: Journal of Clinical Investigation (1973)

Measurement of the relative absorption rates of inert gases (H2, He, CH4, SF6, and 133Xe) was used to investigate the interaction between diffusion and blood flow during passive absorption from the stomach, small bowel, and colon of the rat. If uptake is blood flow limited, the gases should be absorbed in proportion to their solubilities in blood, but if diffusion limited, uptake should be proportional to the diffusion rate of the gases in mucosal tissues.
COMPARISON OF THE TOLERANCE OF ADULTS AND CHILDREN TO DIGITOXIN
Authors: Sydney Mathes
Journal: JAMA (1952)

The utility of digitalis therapy in children is a subject of much controversy. That this group of drugs is not as effective in children as it is in adults is generally accepted, but there is the belief, fairly widely held among those familiar with the problems of heart disease in children, that digitalis therapy may be injurious to children with heart disease and failure. Sutton and Wyckoff<sup>1</sup>studied the effect of digitalis in heart failure among a group of children and concluded that the drug is useful, and in dosages,approximately similar to those for adults. Jacobsen and Davison<sup>2</sup>found digitalis effective in children with active carditis and failure, but in larger doses than those required by adults on the basis of body weight. Jezer and Schwartz<sup>3</sup>gave very large doses of digitalis to a group of children in congestive failure; from this experience they concluded that the
Laparoscopic cholecystectomy without visible scar: combined transvaginal and transumbilical approach
Authors: C. Zornig, A. Emmermann, H. Waldenfels, H. Mofid
Journal: Endoscopy (2007)

Laparoscopic surgery has decreased trauma and improved results and natural orifice transluminal endoscopic surgery (NOTES) should be a further step in this direction. However the use of flexible gastroscopes in the abdomen is difficult and the generally chosen transgastric approach is not without risk. Therefore we have carried out a cholecystectomy with a combined transvaginal and transumbilical approach, using laparoscopic instruments. The optic and a dissector were inserted in the posterior fornix of the vagina, and a 5-mm trocar was inserted deep in the umbilicus. After dissection the gallbladder was removed through the vagina. The operation was done without problems within 85 minutes and left no visible scar. The postoperative course was uneventful. In NOTES the transvaginal approach has important advantages over the transgastric method (e. g. regarding sterilization and closure); standard laparoscopic instruments can be used whilst there are no flexible endoscopes that are easier to handle.
Video-imaging of lumen narrowing; muscle shortening and flow responsiveness in isolated bronchial segments of the pig
Authors: HW Mitchell, MP Sparrow
Journal: European Respiratory Journal (1994)

The amount of smooth muscle shortening required to cause narrowing of the bronchial lumen and to significantly alter airflow in an airway has not not been measured. Accordingly, in this study, the lumens of isolated fluid-filled bronchial segments from pigs were directly visualized using a fibreoptic endoscope and video-recording. The extent of lumen narrowing was related to smooth muscle contraction, determined morphometrically, and to bronchial lumen flow. Narrowing was produced by electrical field stimulation (EFS), (70 V, 20 Hz, 2-3 ms) and acetylcholine (ACh), (10(-5)-10(-2) M). The diameter of the relaxed bronchial lumen and the reduction in diameter produced by maximum electrical field stimulation were both greater when the transmural pressure was increased (from -8 to 20 cmH2O). The percentage change in diameter produced by electrical field stimulation was not, however, significantly different over this pressure range. Electrical field stimulation caused the bronchial lumen to narrow by 28.5 +/- 3.3% in diameter, and by 45.7 +/- 3.8% in cross-sectional area, at zero transmural pressure. Maximum doses of acetylcholine (10(-2) M) reduced the lumen diameter by 48.3 +/- 3.3%, and the area by 70.3 +/- 4.8%. In separate experiments, maximum doses of ACh stopped the flow of Krebs solution perfused through the lumen of bronchial segments. Morphometric measurements indicated that smooth muscle shortened by a maximum of 32.5 +/- 2.8% to acetylcholine 10(2) M, relative to fully-relaxed dimensions. Simultaneous imaging of the lumen and adventitia of bronchi showed that the luminal margin narrowed more than the adventitia.(ABSTRACT TRUNCATED AT 250 WORDS)
Sex difference in response of the human sebaceous gland to topical flutamide
Authors: FERGUS LYONS, SAM SHUSTER
Journal: British Journal of Dermatology (1982)

Sebum excretion rate (SER) was measured before and 4–6 weeks after topical application of flutamide or its hydroxylated metabolite to the forehead skin of eighteen patients with acne. There was a significant difference in response between males and females, SER decreasing by a mean of 22% in males and increasing by a mean of 26% in females.
Adventitial growth factor signalling and vascular remodelling: Potential of perivascular gene transfer from the outside-in
Authors: R SIOW, A CHURCHMAN
Journal: Cardiovascular Research (2007)

The adventitial segment of the vessel wall has received limited attention compared the endothelium, media and neointima in processes involved in vascular remodelling during atherogenesis, coronary artery bypass graft failure and in response to angioplasty. The adventitia has been regarded as a relatively 'inert' layer providing a supportive connective tissue and extracellular matrix scaffold around vessels for nerves and the vasa vasorum. We and others have recently demonstrated that functional changes in cells within the adventitia contribute to vascular remodelling through the activation and migration of adventitial myofibroblasts, partly under the influence of transforming growth factor-beta1 and platelet derived growth factor-BB. These cytokines stimulate local accumulation of progenitor cells, angiogenesis, matrix deposition and enhanced generation of reactive oxygen species, together contributing to intimal hyperplasia in vascular diseases. This review summarises the evidence that growth factors acting locally in the adventitia can influence vascular function. Furthermore we highlight the therapeutic potential of perivascular gene transfer approaches from the 'outside-in' to antagonise growth factor activity and to modulate expression of vaso- and redox-active genes which act in concert to prevent the progression of vascular diseases in which adventitial cells are activated.
Sentinel systems are needed for long term adverse drug reactions
Authors: Torbjörn Callréus
Journal: BMJ (2005)

EDITOR—In the wake of the withdrawal of rofecoxib, the limitation of the current system of pharmacovigilance is once again under discussion. With the system's focus on spontaneous reports, unexpected and rare reactions occurring shortly after exposure are usually detected with reasonable sensitivity. However, adverse effects are not readily identified if they occur after long time exposure or manifest themselves as an increase …
Study was not designed to test the hypothesis
Authors: Karen M Silvers, Michael J Epton, Chris M Frampton
Journal: BMJ (2007)

The PROBIT study is a large randomised controlled study aimed at reducing childhood gastrointestinal infection by promoting breast feeding. Secondary outcomes included atopic eczema and asthma.1 However, the recent paper was written as if the study's main aim was to test the association between prolonged and exclusive breast feeding and asthma and allergy.2 When no statistical difference was found, the authors erroneously concluded …
THE EFFECT OF EGG YOLK IN DIETS ON ANAPHYLACTIC ARTHRITIS (PASSIVE ARTHUS PHENOMENON) IN THE GUINEA PIG
Authors: Alvin F. Coburn, Claire E. Graham, Joan Haninger
Journal: The Journal of Experimental Medicine (1954)

WHOLE EGG YOLK INCORPORATED AS A SUPPLEMENT IN THE DIET OF BABY GUINEA PIGS AFFORDED PROTECTION AGAINST ANAPHYLACTIC ARTHRITIS AS DETERMINED: (a) by measurement of joint swelling; (b) by the rise in serum level of some substance which reacts with diphenylamine; (c) by histologic examination. The active material in egg yolk was shown to be in the alcohol-soluble fraction. Attempts to identify the active material with any known lipid have to date been unsuccessful. In the screening of lipid substances for protection against anaphylactic arthritis, it is shown that the weanling guinea pig is suitable, that a 3 week period is adequate, and that the test substance can be administered satisfactorily in the diet.
Androgen-Independent Growth and Tumorigenesis of Prostate Cancer Cells Are Enhanced by the Presence of PKA-Differentiated Neuroendocrine Cells
Authors: Paul D. Deeble, Michael E. Cox, Henry F. Frierson, Robert A. Sikes, Jodie B. Palmer, Robert J. Davidson, Eli V. Casarez, George P. Amorino, Sarah J. Parsons
Journal: Cancer Research (2007)

Abstract The neuroendocrine status of prostatic adenocarcinomas is considered a prognostic indicator for development of aggressive, androgen-independent disease. Neuroendocrine-like cells are thought to function by providing growth and survival signals to surrounding tumor cells, particularly following androgen ablation therapy. To test this hypothesis directly, LNCaP cells were engineered to inducibly express a constitutively activated form of the cyclic AMP–dependent protein kinase A catalytic subunit (caPKA), which was previously found upon transient transfection to be sufficient for acquisition of neuroendocrine-like characteristics and loss of mitotic activity. Clonal cells that inducibly expressed caPKA enhanced the growth of prostate tumor cells in anchorage-dependent and anchorage-independent in vitro assays as well as the growth of prostate tumor xenografts in vivo, with the greatest effects seen under conditions of androgen deprivation. These results suggest that neuroendocrine-like cells of prostatic tumors have the potential to enhance androgen-independent tumor growth in a paracrine manner, thereby contributing to progression of the disease. [Cancer Res 2007;67(8):3663–72]
Abnormal Rheologic Effects of Glyceryl Trinitrate in Patients with Non-Insulin-Dependent Diabetes Mellitus and Reversal by Antioxidants
Authors: Dario Giugliano
Journal: Annals of Internal Medicine (1995)

Objective: To evaluate 1) the hemorrheologic and hemodynamic effects of glyceryl trinitrate in patients with non–insulin-dependent diabetes mellitus and 2) the influence of antioxidants on these effects. Design: Case-control study. Setting: University hospital clinic. Patients: 40 patients with diabetes and no evidence of cardiovascular complications and 40 controls matched for demographic variables and body habitus. Interventions: Sublingual glyceryl trinitrate (0.3 mg) and transdermal glyceryl trinitrate patches (10 mg/d). Vitamin E, 300 mg/d orally for 7 days, and glutathione, 600 mg intravenously or intramuscularly, were given to test the effects of antioxidant supplementation. Measurements: Systolic, diastolic, and mean arterial pressure and heart rate; left ventricular ejection fraction; platelet aggregation, blood viscosity, and blood filterability in vitro and ex vivo. Results: Compared with controls, patients with diabetes had increased platelet aggregation to adenosine diphosphate (P < 0.005), increased blood viscosity (P < 0.001), and decreased blood filterability (P = 0.041) at baseline; blood pressure, heart rate, and ejection fraction were similar in the two groups. In controls, both sublingual glyceryl trinitrate and transdermal glyceryl trinitrate patches significantly reduced platelet aggregation (−38%; 95% CI, −49% to −27%) and blood viscosity (−8%; CI, −11% to −5%) and increased blood filterability (10%; CI, 7.0% to 13.1%). Slight but significant decreases in blood pressure and ejection fraction and an increase in heart rate were also seen in controls after administration of glyceryl trinitrate (both preparations). In patients with diabetes, glyceryl trinitrate paradoxically increased platelet aggregation (24%; CI, 15% to 33%) and blood viscosity (6%; CI, 2.9% to 8.8%) and decreased blood filterability (−7%; CI, −9.5% to −4.4%); hemodynamic values did not change significantly. In both groups, rheologic responses to glyceryl trinitrate (end concentration, 100 and 200 ng/mL) in vitro were similar to those seen in ex vivo studies. Vitamin E and glutathione normalized rheologic responses to glyceryl trinitrate in patients with diabetes. Conclusions: Organic nitrates have beneficial effects on blood rheology in controls but not in patients with diabetes, in whom a paradoxical deterioration is seen. Antioxidant supplementation can normalize primary tolerance to the rheologic effects of nitrates in diabetes.
THE ASSOCIATION OF SINUS DISEASE AND MIDDLE EAR INFECTION
Authors: M. M. CULLOM
Journal: JAMA (1934)

The conclusions arrived at in this paper are based on more than one hundred cases of mastoiditis in private patients which I have observed since the influenza epidemic of 1918. A great many mastoid operations were performed in my clinic at the Vanderbilt Hospital. As I did not perform these operations it was not possible to get a thorough examination of the sinuses in connection with the mastoiditis, so those cases have not been taken into account. The case histories of these patients read so much like the histories of the patients that were carefully examined with respect to their sinuses, however, that it leaves no doubt in my mind that sinusitis was present in these cases to a very large per cent.  Following the epidemic of influenza in 1918 there were a great many cases of mastoiditis. There were also many cases of sinus infection. The association of sinus
Methylene chloride poisoning in a cabinet worker.
Authors: M Mahmud, S N Kales
Journal: Environmental Health Perspectives (1999)

More than a million workers are at risk for methylene chloride exposure. Aerosol sprays and paint stripping may also cause significant nonoccupational exposures. After methylene chloride inhalation, significant amounts of carbon monoxide are formed in vivo as a metabolic by-product. Poisoning predominantly affects the central nervous system and results from both carboxyhemoglobin formation and direct solvent-related narcosis. In this report, we describe a case of methylene chloride intoxication probably complicated by exogenous carbon monoxide exposure. The worker's presentation of intermittent headaches was consistent with both methylene chloride intoxication and carbon monoxide poisoning. The exposures and symptoms were corroborated by elevated carboxyhemoglobin saturations and a workplace inspection that documented significant exposures to both methylene chloride and carbon monoxide. When both carbon monoxide and methylene chloride are inhaled, additional carboxyhemoglobin formation is expected. Preventive efforts should include education, air monitoring, and periodic carboxyhemoglobin determinations. Methylene chloride should never be used in enclosed or poorly ventilated areas because of the well-documented dangers of loss of consciousness and death.
T Lymphocytes Negatively Regulate Lymph Node Lymphatic Vessel Formation
Authors: Raghu P. Kataru, Honsoul Kim, Cholsoon Jang, Dong Kyu Choi, Bong Ihn Koh, Minah Kim, Sudheer Gollamudi, Yun-Keun Kim, Seung-Hyo Lee, Gou Young Koh
Journal: Immunity (2011)