tbuckley/cabot-search huggingface dataset:
Dogs with experimental cirrhosis of the liver but without intrahepatic hypertension do not retain sodium or form ascites.
Authors: B Unikowsky, M J Wexler, M Levy
Journal: Journal of Clinical Investigation (1983)

Dogs with portal cirrhosis but without portal hypertension (end-to-side portacaval anastomosis) retain sodium and expand plasma volume before ascites formation. In our study, dogs were subjected to bile duct ligation and simultaneous side-to-side portacaval anastomosis (PCA) in order to create a canine model of hepatic cirrhosis without intrahepatic or portal hypertension. The effect of normalizing intrahepatic pressures in the face of venous outflow block on sodium handling was studied. 13 dogs survived the surgical procedures and were followed. Two dogs developed sodium retention and ascites at 5-6 wk (livers were cirrhotic) when the PCA spontaneously closed. 11 dogs were free of sodium retention and ascites for as long as 12 wks after surgery, while ingesting 35 meq/d of sodium. In this group glomerular filtration rate remained normal throughout the period of observation and there was no expansion of plasma volume. Nine of these dogs were then fed 85 meq/d of sodium; eight remained in sodium balance and one retained sodium and went on to develop ascites. When 10-15 mg i.m. of desoxycorticosterone acetate (DOCA) was given daily, five dogs developed sodium retention and ascites, while four escaped from DOCA. Dogs who developed ascites had either a partially occluded PCA (4/5) or a patent PCA, but with a significant portacaval pressure gradient of 9.5 cm H2O (1/5). In all four dogs who escaped from DOCA, the PCA was widely patent and the mean pressure gradient was only 1.6 cm H2O. Both groups were equally cirrhotic, as judged by histological and biochemical parameters. We conclude that normalizing intrahepatic pressure by providing an outflow tract for the cirrhotic liver will abolish that component of early renal tubular sodium retention not due to portal venous hypertension or ascites sequestration.
The effect of glutathione depletion on14CO2 evolution from [14C] methyl-labeled aminopyrine in intact rats
Authors: Harshika S. Bhatt, Burton Combes
Journal: Hepatology (1985)

The effect of hepatic glutathione depletion on 14 CO 2 evolution from [ 14 C]methyl–labeled aminopyrine was assessed in fed male Sprague–Dawley rats. Within 30 min of i.p. administration of either diethylmaleate or phorone, hepatic glutathione fell approximately 75 to 80% and remained depressed for the ensuing 120 min. [ 14 C]Aminopyrine was i.p. administered 30 min after the glutathione–lowering agents (zero time) and exhaled 14 CO 2 was collected at 15–min intervals for the next 120 min. Parameters of 14 CO 2 exhalation including peak exhalation rate, cumulative exhalation from 0 to 120 min and the elimination rate constant were all impaired in glutathionedepleted rats. Metabolism of the [ 14 C]methyl groups involves N –demethylation with formation of formaldehyde, oxidation to formate and conversion to 14 CO 2 . Glutathione depletion did not affect CO 2 evolution from i.p. administered formate or bicarbonate. The glutathione–dependent step presumably involves either or both generation of formaldehyde or its subsequent oxidation to formate.
VITAMIN DEFICIENCIES AND THE SMALL INTESTINE
Authors: THOMAS T. MACKIE
Journal: JAMA (1941)

Functional changes in the small intestine demonstrable by roentgen examination were first noted in a case of nontropical sprue.<sup>1</sup>Shortly thereafter they were observed to occur in chronic idiopathic steatorrhea,<sup>2</sup>in association with the mixed deficiency states complicating chronic ulcerative colitis<sup>3</sup>and in tropical sprue.<sup>4</sup>They have likewise been shown to occur in infantile celiac disease.<sup>5</sup>It is of interest that, although all these conditions may be and often are accompanied by a macrocytic anemia, the characteristic changes in the small intestine have not been observed in pernicious anemia.<sup>6</sup> The deficiency pattern of the small intestine, however, may occur in a variety of conditions, as nephrosis and diabetes insipidus,<sup>7</sup>icterus with absence of bile from the intestine,<sup>8</sup>diseases of the mesenteric lymphatics, and intra-abdominal cancer. It is probably significant that exactly the same pattern is presented by the intestine of the normal
A regulatory dendritic cell signature correlates with the clinical efficacy of allergen-specific sublingual immunotherapy
Authors: Aline Zimmer, Julien Bouley, Maxime Le Mignon, Elodie Pliquet, Stéphane Horiot, Mathilde Turfkruyer, Véronique Baron-Bodo, Friedrich Horak, Emmanuel Nony, Anne Louise, Hélène Moussu, Laurent Mascarell, Philippe Moingeon
Journal: Journal of Allergy and Clinical Immunology (2012)
TRAP1 Is Involved in BRAF Regulation and Downstream Attenuation of ERK Phosphorylation and Cell-Cycle Progression: A Novel Target for BRAF-Mutated Colorectal Tumors
Authors: Valentina Condelli, Annamaria Piscazzi, Lorenza Sisinni, Danilo Swann Matassa, Francesca Maddalena, Giacomo Lettini, Vittorio Simeon, Giuseppe Palladino, Maria Rosaria Amoroso, Stefania Trino, Franca Esposito, Matteo Landriscina
Journal: Cancer Research (2014)

Human BRAF-driven tumors are aggressive malignancies with poor clinical outcome and lack of sensitivity to therapies. TRAP1 is a HSP90 molecular chaperone deregulated in human tumors and responsible for specific features of cancer cells, i.e., protection from apoptosis, drug resistance, metabolic regulation, and protein quality control/ubiquitination. The hypothesis that TRAP1 plays a regulatory function on the BRAF pathway, arising from the observation that BRAF levels are decreased upon TRAP1 interference, was tested in human breast and colorectal carcinoma in vitro and in vivo. This study shows that TRAP1 is involved in the regulation of BRAF synthesis/ubiquitination, without affecting its stability. Indeed, BRAF synthesis is facilitated in a TRAP1-rich background, whereas increased ubiquitination occurs upon disruption of the TRAP1 network that correlates with decreased protein levels. Remarkably, BRAF downstream pathway is modulated by TRAP1 regulatory activity: indeed, TRAP1 silencing induces (i) ERK phosphorylation attenuation, (ii) cell-cycle inhibition with cell accumulation in G0-G1 and G2-M transitions, and (iii) extensive reprogramming of gene expression. Interestingly, a genome-wide profiling of TRAP1-knockdown cells identified cell growth and cell-cycle regulation as the most significant biofunctions controlled by the TRAP1 network. It is worth noting that TRAP1 regulation on BRAF is conserved in human colorectal carcinomas, with the two proteins being frequently coexpressed. Finally, the dual HSP90/TRAP1 inhibitor HSP990 showed activity against the TRAP1 network and high cytostatic potential in BRAF-mutated colorectal carcinoma cells. Therefore, this novel TRAP1 function represents an attractive therapeutic window to target dependency of BRAF-driven tumors on TRAP1 translational/quality control machinery.
Potential Physician Malpractice Liability Associated with Complementary and Integrative Medical Therapies
Authors: Michael H. Cohen, David M. Eisenberg
Journal: Annals of Internal Medicine (2002)

Physicians are increasingly grappling with medical liability issues as complementary and integrative health care practices are made available in conventional medical settings. This article proposes a framework in which physicians can assess potential malpractice liability issues in counseling patients about complementary and integrative therapies. The framework classifies complementary and integrative therapies according to whether the evidence reported in the medical and scientific literature supports both safety and efficacy; supports safety, but evidence regarding efficacy is inconclusive; supports efficacy, but evidence regarding safety is inconclusive; or indicates either serious risk or inefficacy. Clinical examples in each category help guide the clinician on how to counsel patients regarding use of complementary and alternative medical therapies in a given clinical situation. Specific strategies to reduce the risk for potential malpractice liability include the following: 1) determine the clinical risk level; 2) document the literature supporting the therapeutic choice; 3) provide adequate informed consent; 4) continue to monitor the patient conventionally; and 5) for referrals, inquire about the competence of the complementary and alternative medicine provider. This framework provides a basis for clinical decisions involving complementary and integrative care.
Carbenicillin-Associated Hypokalemic Alkalosis
Authors: Sergio V. Cabizuca
Journal: JAMA (1976)

IN 1968, Brunner and Frick reported severe metabolic alkalosis and hypokalemia in patients receiving large doses of penicillin G sodium.<sup>1</sup>It was suggested that penicillin promoted urinary potassium excretion by acting as a nonreabsorbable anion. Subsequently, correspondence in the medical literature implicated carbenicillin as another possible cause of hypokalemic alkalosis.<sup>2-4</sup>We report here the development of hypokalemia, hypochloremia, and metabolic alkalemia during the course of intravenous administration of carbenicillin disodium in a patient with pulmonary<i>Pseudomonas</i>infection. Serial arterial blood gas studies clearly demonstrated metabolic alkalosis in this patient. <h3>Report of a Case</h3> A 61-year-old woman had a recent thoracotomy and biopsy of a mass that demonstrated squamous cell carcinoma of the right upper lobe with metastases to the pleura and regional lymph nodes. After a week's course of postoperative radiation therapy, there was an onset of fever and a productive cough. Two sputum cultures were positive for
Mitral-Valve Prolapse Syndrome
Authors: Richard L. Popp
Journal: JAMA (1976)

THE MITRAL-VALVE prolapse (MVP) syndrome is a relatively recently recognized association of various signs and symptoms. Systolic clicks, late systolic murmurs, or both have been heard by clinicians for a number of years. More than ten years ago, patients with these auscultatory findings were found to have angiographic evidence of billowing of the mitral-valve leaflets toward the left atrium during systole, frequently in association with mild mitral regurgitation.<sup>1</sup>This led to the use of these auscultatory findings as the sine qua non of the syndrome. The recent identification of preclinical and mildly symptomatic forms of MVP by echocardiography has stimulated us to reassess this condition.<sup>2</sup>We now realize that this syndrome is composed of many signs and symptoms, causing only minor degrees of disability at times. This article enumerates the elements of this fascinating syndrome as classically described and adds information gained by echocardiography. This additional information broadens
Peritoneal Sodium Transport During Hypertonic Peritoneal Dialysis
Authors: Karl D. Nolph, Jessie E. Hano, Paul E. Teschan
Journal: Annals of Internal Medicine (1969)

Hypertonic peritoneal dialysis is frequently utilized to remove excess sodium and water from the body. It is shown that the ultrafiltrate is probably of extracellular origin and is invariably hyponatric to serum. Sodium accompanies the bulk flow of water in varying amounts from patient to patient. Factors that influence the transperitoneal transport of sodium, in response to slight diffusion gradients and the solvent drag effect of bulk flow, seem to include peritoneal membrane permeability and the extracellular anionic environment. A method for the proper management of sodium and water removal by hypertonic peritoneal dialysis is described by which hypernatremia, a frequently reported complication, may be prevented. The increase in serum sodium concentration results from the proportionally greater removal of extracellular water than sodium and is not dependent on the development of hyperglycemia or sodium diffusion from dialysate to extracellular fluid, as has been previously reported.
Loss of Primary Cilia Upregulates Renal Hypertrophic Signaling and Promotes Cystogenesis
Authors: P. Darwin Bell, Wayne Fitzgibbon, Kelli Sas, Antine E. Stenbit, May Amria, Amber Houston, Ryan Reichert, Sandra Gilley, Gene P. Siegal, John Bissler, Mehmet Bilgen, Peter Cheng-te Chou, Lisa Guay-Woodford, Brad Yoder, Courtney J. Haycraft, Brian Siroky
Journal: Journal of the American Society of Nephrology (2011)

Primary cilia dysfunction alters renal tubular cell proliferation and differentiation and associates with accelerated cyst formation in polycystic kidney disease. However, the mechanism leading from primary ciliary dysfunction to renal cyst formation is unknown. We hypothesize that primary cilia prevent renal cyst formation by suppressing pathologic tubular cell hypertrophy and proliferation. Unilateral nephrectomy initiates tubular cell hypertrophy and proliferation in the contralateral kidney and provides a tool to examine primary cilia regulation of renal hypertrophy. Conditional knockout of the primary cilia <i>ift88</i> gene leads to delayed, adult-onset renal cystic disease, which provides a window of opportunity to conduct unilateral nephrectomy and examine downstream kinetics of renal hypertrophy and cyst formation. In wild-type animals, unilateral nephrectomy activated the mTOR pathway and produced appropriate structural and functional hypertrophy without renal cyst formation. However, in <i>ift88</i> conditional knockout animals, unilateral nephrectomy triggered increased renal hypertrophy and accelerated renal cyst formation, leading to renal dysfunction. mTOR signaling also increased compared with wild-type animals, suggesting a mechanistic cascade starting with primary ciliary dysfunction, leading to excessive mTOR signaling and renal hypertrophic signaling and culminating in cyst formation. These data suggest that events initiating hypertrophic signaling, such as structural or functional loss of renal mass, may accelerate progression of adult polycystic kidney disease toward end-stage renal disease.
THE CAPACITY OF THE CORONARY BED IN CARDIAC HYPERTROPHY
Authors: William Dock
Journal: The Journal of Experimental Medicine (1941)

After eliminating vascular rigor, perfusing human hearts with kerosene under pressure postmortem gives values for coronary flow which seem an index of the maximum possible flow during life. This is 3.1 cc. per gm. per minute at 100 mm. Hg in normal men under 40. It is 35 per cent lower in the hearts of those 60 to 80 years old, and also falls in hypertrophied hearts. In old people it is 30 per cent lower in hearts over 600 gm. than in those under 350; in patients 40 to 60 years old it is 37 per cent less in hearts over 600 as compared with those under 350 gm. In discussion it is brought out that while the decrease in coronary capacity associated with age or hypertrophy may play a part in predisposing some hearts to congestive failure, there is no evidence that the hypertrophied heart has an inadequate oxygen supply or that its fibers are too thick for adequate oxygen diffusion. Congestive failure cannot be ascribed to anoxia except in the presence of severe anemia, coronary occlusion, or tachycardia with low blood pressure. Decrease in perfusibility with age and growth may be a perfectly normal adaptation to the needs of the tissue; the perfusibility of the heart of the young adult is about half that of an infant at 2 years.
Adherence to Statin Therapy Under Drug Cost Sharing in Patients With and Without Acute Myocardial Infarction
Authors: Sebastian Schneeweiss, Amanda R. Patrick, Malcolm Maclure, Colin R. Dormuth, Robert J. Glynn
Journal: Circulation (2007)

As medication spending grows, Medicare Part D will need to adapt its coverage policies according to emerging evidence from a variety of insurance policies. We sought to evaluate the consequences of copayment and coinsurance policies on the initiation of statin therapy after acute myocardial infarction and adherence to therapy in statin initiators using a natural experiment of all British Columbia residents aged 66 years and older.Three consecutive cohorts that included all patients who began statin therapy during full drug coverage (2001), coverage with a $10 or $25 copay (2002), and coverage with a 25% coinsurance benefit (2003-2004) were followed up with linked healthcare utilization data (n=51,561). Follow-up of cohorts was 9 months after each policy change. Adherence to statin therapy was defined as > or = 80% of days covered. Relative to full-coverage policies, adherence to new statin therapy was significantly reduced, from 55.8% to 50.5%, under a fixed copayment policy (-5.4% points; 95% CI, -6.4% to -4.4%) and the subsequent coinsurance policy (-5.4% points; 95% CI, -6.3% to -4.4%). An uninterrupted increase in the proportion of patients initiating statin therapy after an acute myocardial infarction (1.7% points per quarter) was observed over the study period, similar to a Pennsylvania control population with full coverage. Sudden changes to full out-of-pocket spending, similar to Medicare's Part D "doughnut hole," almost doubled the risk of stopping statins (adjusted odds ratio, 1.94, 95% CI, 1.82 to 2.08).Fixed patient copayment and coinsurance policies have negative effects on adherence to statin lipid-lowering drug therapy but not on their initiation after myocardial infarction.
Coexistence of Renal Arterial Hypertension and Diabetes Mellitus
Authors: Alvin P. Shapiro
Journal: JAMA (1965)

The incidence of diabetes mellitus was noted to be 44% in a group of 55 hypertensive subjects with renal arterial stenosis. The hypertension in these individuals was quite variable, ranging from mild to malignant. Their mean age was less than 53 years. Impairment of renal function was only mild to moderate in the majority of the subjects. The high incidence can be interpreted as favoring the concept that renal-artery stenosis is often secondary to essential hypertension and an increased tendency to atherosclerosis, rather than a primary phenomenon in the development of hypertension. Alternatively, it may provide an explanation for some cases of severe hypertension among diabetics, particularly when mild hypertension becomes accelerated and severe. The theoretical and statistical problems pertaining to this interpretation are briefly discussed. The report emphasizes the need to investigate clinically for renal-artery disease in hypertensive diabetics and for diabetes in renal hypertensive subjects.
Estrogen and Progestin Compared with Simvastatin for Hypercholesterolemia in Postmenopausal Women
Authors: Giselle M. Darling, Jennifer A. Johns, Philip I. McCloud, Susan R. Davis
Journal: New England Journal of Medicine (1997)

Postmenopausal estrogen therapy has favorable effects on serum lipoproteins in women with normal serum lipid levels, but the effect of combined estrogen and progestin therapy on lipoproteins in women with hypercholesterolemia has not been determined, nor has it been directly compared with the effect of conventional lipid-lowering therapy.In a randomized crossover trial, we studied 58 postmenopausal women with fasting serum total cholesterol levels greater than 250 mg per deciliter. Each woman received simvastatin (10 mg daily) for eight weeks and postmenopausal hormone therapy (up to 1.25 mg of conjugated equine estrogens daily, along with 5 mg of medroxyprogesterone acetate daily) for eight weeks, with an eight-week washout period between the two treatment phases.At base line, the mean (+/-SD) cholesterol values were as follows: total cholesterol, 305+/-39 mg per deciliter; high-density lipoprotein (HDL) cholesterol, 62+/-19 mg per deciliter; and low-density lipoprotein (LDL) cholesterol, 217+/-39 mg per deciliter. For total cholesterol, the mean decrease with hormone therapy was 14 percent (95 percent confidence interval, 11 to 16 percent) and the mean decrease with simvastatin was 26 percent (95 percent confidence interval, 23 to 29 percent). For LDL cholesterol, the mean decrease was 24 percent (95 percent confidence interval, 20 to 28 percent) with hormone therapy and 36 percent (95 percent confidence interval, 32 to 40 percent) with simvastatin. The effect of simvastatin was significantly greater than that of hormone therapy (P<0.001). HDL cholesterol increased similarly with hormone therapy (mean increase, 7 percent; 95 percent confidence interval, 2 to 12 percent) and simvastatin (mean increase, 7 percent; 95 percent confidence interval, 4 to 10 percent). Triglyceride levels increased with hormone therapy (mean increase, 29 percent; 95 percent confidence interval, 15 to 42 percent) but decreased with simvastatin (mean decrease, 14 percent; 95 percent confidence interval, 8 to 20 percent). Lp(a) lipoprotein decreased with hormone therapy (mean decrease, 27 percent; 95 percent confidence interval, 20 to 34 percent), but not with simvastatin.In postmenopausal women with hypercholesterolemia, therapy with estrogen plus progestin has beneficial effects on lipoprotein levels. Hormone therapy may be an effective alternative to treatment with simvastatin, especially in women with normal triglyceride levels.
Endothelial renin-angiotensin pathway. Adrenergic regulation of angiotensin secretion.
Authors: S S Tang, L Stevenson, V J Dzau
Journal: Circulation Research (1990)

Cultured bovine aortic endothelial cells (BAECs) express the complete renin-angiotensin system and secrete angiotensins. In this study, we examined the adrenergic influence on the secretion of angiotensins from BAECs. Angiotensins were determined by high-performance liquid chromatography and radioimmunoassay. At basal state, BAECs contain angiotensin I, angiotensin II, and angiotensin III at concentrations of 2.5 +/- 1.3, 4.8 +/- 2.3, and 3.4 +/- 1.5 pg/10(6) cells, respectively. Angiotensin I, angiotensin II, and angiotensin III concentrations in the culture medium were 8.3 +/- 4.4, 9.4 +/- 3.5, and 9.9 +/- 3.3 pg/10(6) cells, respectively. Isoproterenol (0.1-10 microM) increases secretion of angiotensins I, II, and III in a dose-dependent manner. Increase in angiotensin secretion induced by isoproterenol (10 microM) can be inhibited by beta 2-adrenoceptor antagonist ICI 118,551 (1 microM), but not by beta 1-adrenoceptor antagonist atenolol (1 microM). Forskolin (1-1,000 microM) mimics the isoproterenol-induced response. In contrast, alpha-adrenergic agonist phenylephrine (1-100 microM) inhibits the secretion. Pretreatment of BAECs with captopril (1 microM) inhibits the accumulation of angiotensin II and angiotensin III in the culture medium, but not angiotensin I. These findings suggest that BAEC production and/or secretion of angiotensins is regulated by adrenergic mechanisms.
Cd26/Dipeptidyl Peptidase IV in Context
Authors: Satoshi Iwata, Chikao Morimoto
Journal: The Journal of Experimental Medicine (1999)

CD26, the T cell activation molecule, is a 110-kD glycoprotein that is also present on epithelial cells of various tissues, including the liver, kidney, and intestine. CD26 possesses a known dipeptidyl peptidase (DPP)IV activity in its extracellular domain ([1][1]). A paper by Wesley et al. in this
Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells
Authors: Yongchao Wang, Warren Fiskus, Daniel G. Chong, Kathleen M. Buckley, Kavita Natarajan, Rekha Rao, Atul Joshi, Ramesh Balusu, Sanjay Koul, Jianguang Chen, Andrew Savoie, Celalettin Ustun, Anand P. Jillella, Peter Atadja, Ross L. Levine, Kapil N. Bhalla
Journal: Blood (2009)