tbuckley/cabot-search huggingface dataset:
Continuous increase of alcohol dehydrogenase activity along the liver plate in normal and cirrhotic human livers
Authors: Etienne Marc Sokal, Elizabeth Collette, Jean Paul Buts
Journal: Hepatology (1993)

To determine the zonal distribution of alcohol dehydrogenase in normal and cirrhotic human livers, we measured activities of this enzyme by quantitative cytochemical analysis along the liver cell plate in liver specimens from 10 normal organ donors and from 7 children with extrahepatic biliary atresia cirrhosis. In normal human liver samples, a continuous increase in alcohol dehydrogenase activity was observed along the sinusoid from the periportal to the perivenular hepatocytes (mean extinction units from 16.2 +/- 10.0 to 58.0 +/- 14.8). A similar observation was made in cirrhotic nodules, with activity increasing continuously from nodule periphery to center (7.6 +/- 4.1 to 44.9 +/- 13.3). This study demonstrates a heterogeneous pattern of alcohol dehydrogenase distribution along the sinusoid in normal human liver specimens. In addition, demonstration of this heterogeneity in human cirrhosis suggests that the cirrhotic liver is able to maintain a parenchymal functional organization, with persistence of metabolic zonation.
Abstract A27: Mapping of chemical-genetic interactions in breast cancer reveals a mechanism of resistance to PI3K inhibitors
Authors: Markus K. Muellner, Iris Z. Uras, Bianca Gapp, Sebastian M. Nijman
Journal: Cancer Research (2012)

Abstract Linking the molecular aberrations of cancer to drug responses allows directing the choice of treatment and to explore new therapeutic applications. We set out to systematically map drug-gene interactions in breast cancer and established a multiplexed assay to study the cellular fitness of a panel of engineered isogenic cells in response to a collection of drugs. This approach so far revealed several synthetic-lethal interactions and drug-resistance mechanisms, including previously discovered interactions from other model systems. Among the novel interactions NOTCH pathway activation, which occurs frequently in breast cancer, unexpectedly conferred resistance to phosphoinositide 3-kinase (PI3K) inhibitors, which are currently undergoing clinical trials in breast cancer patients. NOTCH1 and downstream induction of c-MYC over-rode the dependency of cells on the PI3K-mTOR pathway for proliferation. These data reveal a new mechanism of resistance to PI3K inhibitors with direct clinical implications. Citation Format: Markus K. Muellner, Iris Z. Uras, Bianca Gapp, Sebastian M. Nijman. Mapping of chemical-genetic interactions in breast cancer reveals a mechanism of resistance to PI3K inhibitors [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr A27.
AB1436-HPR Predictors of outcome of multidisciplinary treatment in chronic widespread pain: An observational study
Authors: A. De Rooij, M. van der Leeden, L.D. Roorda, M.P. Steultjens, J. Dekker
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The effectiveness of multidisciplinary treatment in chronic widespread pain (CWP) is limited. The considerable heterogeneity among patients is a likely explanation. Knowledge on predictors of the outcome of multidisciplinary treatment can help to optimize treatment effectiveness. <h3>Objectives</h3> To identify predictors of multidisciplinary treatment outcome in patients with chronic wide spread pain (CWP) <h3>Methods</h3> Data were used from baseline and 6 months follow-up measurements of a prospective cohort study of 120 CWP. Regression models were used to assess whether baseline variables predicted treatment outcome. Outcome domains included: pain, pain interference, depression, and global perceived effect (GPE). Potential predictors included: psychological distress, illness and self-efficacy beliefs, fear-avoidance beliefs and behaviour, symptoms, disability, and socio-demographic factors. <h3>Results</h3> Greater improvement in pain was predicted by more pain at baseline and male gender. Greater improvement in interference of pain in daily life was predicted by more interference of pain in daily life at baseline, lower levels of anxiety, a stronger belief in personal control, less belief in consequences, male gender, and a higher level of education. Greater improvement in depression was predicted by higher baseline values of depression, stronger beliefs in personal control, and a higher level of education. Better outcome on GPE was predicted by less pain, less fatigue, and a higher level of education. <h3>Conclusions</h3> Less anxiety, stronger beliefs in personal control, less belief in consequences, less pain, less fatigue, higher level of education, and male gender are predictors of better outcome of multidisciplinary treatment in CWP. Tailoring treatment to these specific patient characteristics or selecting eligible patients for multidisciplinary treatment may further improve treatment outcome. <h3>Disclosure of Interest</h3> None Declared
A Prospective Study of Lipoprotein(a) and the Risk of Myocardial Infarction
Authors: Paul M. Ridker
Journal: JAMA (1993)

To assess prospectively the risk of myocardial infarction (MI) associated with elevated levels of lipoprotein(a) (Lp[a]).Nested case-control study using prospectively collected plasma samples.Participants in the Physicians' Health Study.A total of 14,916 male physicians aged 40 to 84 years with no prior history of MI or stroke provided plasma samples at baseline and were followed up prospectively for an average period of 60.2 months. Samples from 296 physicians who subsequently developed MI were analyzed for Lp(a) level together with paired controls, matched for smoking status and age.Fatal or nonfatal acute MI.The distribution of Lp(a) level among cases was virtually identical to that of controls (P = .88), and there was no significant difference between groups for median Lp(a) levels (103.0 mg/L vs 102.5 mg/L; P = .73). In analyses controlling for age and smoking status, we found no evidence of association between increasing level of Lp(a) and risk of MI (relative risks from lowest to highest quintiles of Lp(a): 1.00, 0.97, 0.83, 0.88, and 1.07; P for trend = .93) or a threshold effect at any prespecified cutoff of Lp(a) level (relative risks associated with Lp[a] levels above the 25th, 50th, 75th, 90th, and 95th percentiles of the control distribution, respectively: 1.04, 1.00, 1.19, 1.00, and 1.07; all P values nonsignificant). Further adjustment for both lipid and nonlipid cardiovascular risk factors had no material impact.In this prospective study of predominantly middle-aged white men, we found no evidence of association between Lp(a) level and risk of future MI. These data do not support the use of Lp(a) level as a screening tool to define cardiovascular risk among this population.
Glycoproteins: Their Biochemistry, Biology and Role in Human Disease
Authors: Robert G. Spiro
Journal: New England Journal of Medicine (1969)

Properties of GlycoproteinsWith the background on the structure and metabolism of the carbohydrate-containing proteins presented in the first part of this review one can now consider the properties, both chemical and biologic, of some specific groups of glycoproteins.Plasma GlycoproteinsAll the proteins isolated from plasma with the exception of albumin have been shown to contain covalently linked carbohydrate. The plasma glycoproteins were among the first to become the subjects of structural investigations and information about the carbohydrate units of a good number of these has already been obtained, including fetuin,7 the α1-acid glycoprotein,8 α2-macroglobulin,10 transferrin,11 ceruloplasmin, . . .
Ivermectin usage for cheyletiellosis
Authors: Danny W. Scott
Journal: Journal of the American Academy of Dermatology (1998)

I compliment Drs. Cvancara and Elston on their recent cheyletiellosis article (J Am Acad Dermatol 1997;37:265-7). However, they state “To our knowledge, this is the first case of ivermectin (Ivomec) usage for Cheyletiella mite eradication.” This is not the case. Veterninarians have been successfully treating cheyletiellosis in cats, dogs, foxes, and rabbits with the subcutaneous or oral administration of ivermectin since the 1980s.1Malczewski A Kopczewski A Malczewska M Zieli J. Mange due to Cheyletiella blakei in polar foxes in Poland.Zentralb Bakterio [A]. 1984; 258: 412-413Google Scholar, 2Paradis M Villeneuve A. Efficacy of ivermectin against Cheyletiella yasguri infestation in dogs.Can Vet J. 1988; 29: 633-635PubMed Google Scholar, 3Paradis M Scott DW Villeneuve A. Efficacy of ivermectin against Cheyletiella blakei infestation in cats.J Am Anim Hosp Assoc. 1990; 26: 125-128Google Scholar, 4Scott DW Miller Jr, WH Griffin CE. Muller and Kirk’s Small animal dermatology.in: 5th ed. WB Saunders, Philadelphia1996: 412-417Google Scholar
Role of Neutrophils in Myocardial Ischemia and Reperfusion
Authors: Peter Riis Hansen
Journal: Circulation (1995)

In the intact organism, ischemic myocardial injury initiates an acute inflammatory response in which polymorphonuclear leukocytes (PMNs) are major participants. Evidence indicates that the interplaying inflammatory reactions are augmented by reperfusion and that accumulating PMNs can contribute to myocardial damage, eg, by release of oxygen-derived free radicals, proteases, and leukotrienes. In experimental models, interventions aimed at PMN inhibition can exert cardioprotective effects, and some of these strategies raise hope for future clinical applications. A greater understanding of the mechanisms involved in PMN-mediated myocardial damage is necessary for designing a rational approach to reduce the putative detrimental effects of PMNs without antagonizing their favorable consequences in tissue healing.
Regulation of Benzodiazepine Prescription
Authors: Sidney M. Wolfe, Peter Lurie
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Weintraub et al<sup>1</sup>describe their unfavorable assessment of the New York experience with triplicate prescription forms for benzodiazepines as an "independent review." As their study was funded by Hoffmann-LaRoche, Inc, Nutley, NJ, the makers of Valium and Dalmane, the authors seem ill-placed to make such a claim. Indeed, their analysis and data presentation suggest a marked lack of objectivity. The authors use graphs to depict percentage changes rather than absolute changes in numbers of prescriptions. This creates the misleading impression that increases in prescriptions for the alternative drugs might compensate for the diminution in benzodiazepine prescribing (Fig 1, reproduced from Weintraub et al<sup>1</sup>). However, Fig 2, which uses the data from Weintraub et al, illustrates that the absolute increases in the seven alternative drugs are extremely small in comparison with the decrease in benzodiazepine prescribing. In fact, the increase for these alternatives (507 000 prescriptions)
Role of insulin secretagogues in the regulation of somatostatin binding by isolated rat islets.
Authors: P S Mehler, A L Sussman, A Maman, J W Leitner, K E Sussman
Journal: Journal of Clinical Investigation (1980)

To study the possible role of the secretion vesicle inligant-receptor interaction, somatostatin binding was measured in islets in the presence of various substances known to promote secretion vesicle migration and fusion with the plasma membrane and insulin release. Rat islets were incubated with glucose, 30 and 300 mg/dl, for 60 min. After inculation, somatostatin binding was measured. In islets preincubated with glucose, 300 mg/dl, somatostatin binding was increased 250% when compared with glucose, 30 mg/dl (P < 0.001). Concomitant with enhanced somatostatin binding, insulin secretion was increased. Galactose, 300 mg/dl, did not stimulate insulin release, and somatostatin binding was unchanged from control levels. The increase in somatostatin binding with glucose was accounted for by a 186% increase in receptor concentration with no change in receptor affinity. Tolbutamide increased somatostatin binding by more than twofold, accompanied by a similar increase in insulin release. Secretion vesicles isolated from the islet exhibited somatostatin binding. We conclude that, first, somatostatin binding is increased concomitantly with the migration and fusion of the secretion vesicle with the plasma membrane and/or the release of insulin; second, enhanced somatostatin binding occurs as a consequence of an increased receptor concentration; and third, augmented somatostatin binding occurring with hormone release may provide a critical constraint in the regulation of secretory events.
What kind of selection?
Authors: Anne Campbell
Journal: Behavioral and Brain Sciences (2009)

Abstract Supporting a mediating role for fear in inhibiting female aggression, a recent study shows that aversion to “risky” impulsivity completely mediates the sex difference in direct aggression but not in angry acts where dangerous retaliation is unlikely. A more inclusive use of the term “sexual selection” to encompass reproductive advantage would recognise females' crucial role in nurturing and protecting offspring.
A6.29 <i>In vitro</i>protective effects of soluble klotho (SKL) protein on endothelial cells in systemic sclerosis (SSc)
Authors: C Mazzotta, E Romano, S Bellando-Randone, J Blagojevic, S Guiducci, M Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Systemic Sclerosis (SSc) is an autoimmune connective tissue disease characterised by impairs angiogenesis, alterations of microcirculation, senescence and apoptosis of endothelial cells (ECs). A recent study demonstrated that soluble Klotho (sKl) protein interacts with the <i>vascular endothelial growth factor receptor 2</i> (VEGFR-2) and with <i>transient receptor potential canonical-1</i> (TRPC-1) by forming a complex on the surface of endothelial cells. This heterotrimeric complex is internalised in response to <i>vascular endothelial growth factor </i>(VEGF) stimulation, thus regulating VEGFR-2/TRPC-1–mediated Ca<sup>2+</sup> influx, to maintain endothelial biological homeostasis. The aim of this study was to evaluate, if soluble Klotho might act as protective humoral factor on SSc Microvascular Endothelial Cells (MVECs) by inhibiting cellular senescence and inducing angiogenesis. <h3>Materials and methods</h3> Wound healing capacity was performed in healthy and SSc-MVECs under standard conditions and after sKl stimulation. Angiogenesis was evaluated by <i>in vitro</i> capillary morphogenesis on Matrigel in healthy and SSc-MVECs at basal condition, upon challenge with sKl, SSc and healthy sera, and sKl in combination with SSc and healthy sera. Western blot was performed in order to evaluate TRPC-1 and VEGFR-2 expression level in SSc and healthy MVECs at basal condition, after stimulation with sKl, SSc sera (n = 5), healthy sera (n = 5), and with sKl in combination with SSc and healthy sera before and after wound injury. <h3>Results</h3> Wound healing capacity significantly increased in healthy and SSc-MVECs after sKl challenge in respect to basal condition. Angiogenesis was significantly higher in SSc-MVECs upon challenge with sKl compared to both basal SSc and healthy MVEC. Moreover, angiogenesis was significantly increased in healthy MVECs challenged with SSc sera in combination with sKl respect to MVECs with SSc sera alone. TRPC-1 and VEGFR-2 expression level significantly increased under injury in both healthy and SSc-MVECs cultured with sKl respect to basal condition. <h3>Conclusions</h3> Our findings suggest that, under vascular injury conditions, sKl increases the wound healing ability and induces blood vessels formation in SSc-MVECs.
Nestle's donation
Authors: N Adjaye, J R Beesley, N Brewster, A Bush, P F B Carter, E Carter, M Chan, N Cookey, M G Coulthard, S Court, D B Cundall, G Debelle, C Cezateux, G J Ebrahim, D Elliman, D Gibb, R Gilbert, E Hey, W T Houlsby, H Issler, C Jessen, P M Jones, W H Lamb, H J Lambert, C Lazaro, S Lenton, M Levin, M F Lowry, S Logan, A Macfarlan, R Menzies, D C Morley, H M Palmer, C Peckham, C A Porter, E Ross, A N P Speight, N Spencer, J P Stanfield, J E Thomas, A Tomkins, T Waterston, C M Wright, J Wynne, P Zinkin
Journal: BMJ (1994)

EDITOR, — The donation from nestle (UK) Ltd of pounds sterling 140 000 over four years1 is the largest single donation ever received by the British Paediatric Association and should have been debated among the membership. The infant mortality and morbidity worldwide which results from bottle feeding is well known,2 as is the WHO code of practice,3 which is supported by a European directive and, in principle though not yet in law, by the British government. The British …
Magnesium Metabolism in Hypertension
Authors: Robert H. Seller
Journal: JAMA (1965)

Increased vascular smooth-muscle tone and the associated changes in transmembrane potential are thought by several investigators to be a major factor in the development and maintenance of hypertension.<sup>1</sup>Increased extracellular magnesium concentration and diminished cell-membrane permeability are believed to reduce the loss of intracellular potassium and to decrease vascular tone.<sup>2</sup>Conversely, hypomagnesemia has been reported in hypertension and primary aldosteronism which is associated with severe hypertension.<sup>3</sup>In addition, various diuretics, including chlorothiazide, have been shown to affect the urinary excretion of magnesium.<sup>4</sup>It is possible that altered magnesium metabolism through its effect on vascular reactivity, may underlie or contribute to the persistent hypotensive action of the benzothiadiazines. These findings are consistent with the premise that alterations in intracellular magnesium, changes in transmembrane magnesium gradient, or other derangement in magnesium metabolism may facilitate changes in sodium/potassium flux and thereby influence vascular tone. Unfortunately, relatively little is known about
Clinical Evaluation for Sinusitis
Authors: John W. Williams, David L. Simel, LeRoy Roberts, Greg P. Samsa
Journal: Annals of Internal Medicine (1992)

▪ Objective: To identify the most useful clinical examination findings for the diagnosis of acute and subacute sinusitis. ▪ Design: Prospective comparison of clinical findings with radiographs. ▪ Setting: General medicine clinics at a university-affiliated Veterans Affairs Medical Center. ▪ Patients: Two hundred forty-seven consecutive adult men with rhinorrhea (51%), facial pain (22%), or self-suspected sinusitis (27%) (median age, 50 years; median duration of symptoms, 11.5 days). ▪ Measurements: Patients were examined by a principal investigator (86%) or by a staff general internist, internal medicine resident (postgraduate year 2 or 3), or physician assistant, all blinded to radiographic results. All examiners recorded the presence or absence of 16 historical items, 5 physical examination items, and the clinical impression for sinusitis (high, intermediate, or low probability). The criterion standard was paranasal sinus radiographs (4 views), which were interpreted by radiologists blinded to clinical findings. ▪ Results: Thirty-eight percent of patients meeting entrance criteria had sinusitis. Sensitivity, specificity, and likelihood ratios were measured for clinical items. Logistic regression analysis showed five independent predictors of sinusitis: maxillary toothache (odds ratio, 2.9), transillumination (odds ratio, 2.7), poor response to nasal decongestants or antihistamines (odds ratio, 2.4), colored nasal discharge reported by the patient (odds ratio, 2.2), or mucopurulence seen during examination (odds ratio, 2.9). The overall clinical impression was more accurate than any single finding: high probability (likelihood ratio, 4.7), intermediate (likelihood ratio, 1.4), low probability (likelihood ratio, 0.4). ▪ Conclusions: General internists, focusing on five clinical findings and their overall clinical impression, can effectively stratify male patients with sinus symptoms as having a high, intermediate, or low probability of sinusitis.
On a Case of Digital Exploration of the Pylorus (Loreta's Method), with Remarks on the Relation of Gastric Ulceration to Pyloric Stenosis
Authors: C. J. Bond
Journal: BMJ (1889)

the forefinger eventually being passed with ease from the stomach into the duodenum.The hemorrhage was very slight indeed, and the interior of the stomach having been cleansed immediately before the operation no difficulty was experienced with the stomach contents.The wound in the gastric wall was brought together with great accuracy and in a most satisfactory manner by means of Gussenbauer's sutures, which were introduced with specially curved needles, and an interval of about 2 miJlimetres allowed between each.Fine silk was employed.All the stitches were placed in position before aDy were tied.The wound in the ab- dominal wall was closed in the usual manner.August 12th (evening).Patient complaining of pain since the operation; no vomiting.Enemata of milk , iiss, and brandy A ss every eight hours; enemata of port wine every eight hours iij; strychnime gr., glycerini 3ij, aq.ad A ij. 15 drops- 3 gr.hypodermically every four hours.August 13th.Patient slept very little during the night; wind troublesome; passed 101 ounces of urine at 2 A.M. Temperature 100°, pulse 125.Enema of soap and water; no vomiting.August 14th, Patient slept well during the night; passed flatus per rectum, and found great relief; no vomiting.August 15th.Bowels not open; has passed flatus; there is no abdominal distension, but complains still of flatulence; there is some pain in her stomach.August 16th.Very restless during the night; still complains of flatulence; no vomiting.A teaspoonful of gruel every two hours.August 17th.Slept very well during the night; still passing flatus per rectum, causing pain; no vomiting after giving gruel; one stitch removed.6.15 P.M. Iatient comfortable.Supp.morph.gr.I; mitte iij every six hours; enemata of brandy and milk; one teaspoonful of rump steak every four hours; give 10 drops of ac.h ydrochlor.dil. a quarter of an hour before, and then gr.iij of pepsin immediately afterwards.August 18th.Complains of very little pain; still much flatus passing per rectumt; bowels moved at 3.30 p.M.; no vomiting.A teaspoonful of milk and two teaspoonfuls of lime water every four hours alternately with the beef; enemata of milk every four hours; injection of strylch.twice daily gr.-%.August 19th.Wounds dressed; a little discharge; stitches re- moved.August 20th.Wound dressed; looking well; there is a little in-
Oral Administration of a Potent Carbonic Anhydrase Inhibitor (Diamox)
Authors: Arnold S. Relman, Alexander Leaf, William B. Schwartz
Journal: New England Journal of Medicine (1954)

IN a preceding paper1 the metabolic effects of a new potent carbonic anhydrase inhibitor ("Diamox") were reported. In patients with congestive heart failure oral administration of this compound regularly resulted in excretion of an alkaline urine containing increased amounts of potassium and sometimes increased quantities of sodium.The present study was undertaken to evaluate the clinical efficacy of Diamox as a diuretic in patients with severe congestive heart failure. The action of the drug in patients with respiratory acidosis and congestive heart failure due to chronic cor pulmonale is the subject of another report.2 Methods and MaterialsTwenty-six patients with . . .