tbuckley/cabot-search huggingface dataset:
Gap junction-mediated intercellular communication in a long-term primary mouse hepatocyte culture system
Authors: Stephanie A. Stoehr, Harriet C. Isom
Journal: Hepatology (2003)

Gap junction-mediated intercellular communication (GJIC) is critical for maintaining integral cellular processes including differentiation and growth control. The disruption of GJIC has been correlated with aberrant function in many cell types, including hepatocytes in vivo; therefore it is imperative that cellular model systems support intercellular communication to simulate normal cellular functions. Functional GJIC has been shown in long-term primary rat hepatocyte cultures, which have been implemented widely to study various aspects of hepatocellular function; however, the onset of transgenic technology in murine species has necessitated the development of a primary mouse hepatocyte system. In this report, we analyze GJIC in a dimethylsulfoxide (DMSO)-containing long-term primary mouse hepatocyte culture system. The cells retain morphologic and biochemical characteristics of differentiated hepatocytes through day 30 post plating, including liver-specific gene expression. We further show that connexin32 and connexin26 expression and gap junction plaque formation increase over time in culture concomitant with an increase in GJIC between adjoining primary mouse hepatocytes. In conclusion, the findings described in this study make it possible to maintain differentiated primary mouse hepatocytes that also show GJIC in long-term culture for 30 days. In addition, this system has the potential to be extended to study primary mouse hepatocytes isolated from genetically engineered mice.
Fate of Intravenously Administered Gold Nanoparticles in Hair Follicles: Follicular Delivery, Pharmacokinetic Interpretation, and Excretion
Authors: Ivan M. Kempson, Chia‐Chi Chien, Chao‐Yu Chung, Yeukuang Hwu, David Paterson, Martin D. de Jonge, Daryl L. Howard
Journal: Advanced Healthcare Materials (2012)

Abstract Gold nanoparticles (GNPs) are intravenously administered to mice. Deposition at the pilosebacious unit and whiskers is visualized with X‐ray fluorescence after 30 minutes and 14 days. After 30 minutes the dermal papilla, bulge region, and root sheath all contain NPs. GNPs are driven externally out from follicles, counteractive to transfollicular delivery. After 14 days, gold bands in hairs reflect pharmacokinetic profiles indicating blood concentration kinetics. Elimination rate constants infer half‐lives from 3 hairs from an individual mouse within reasonable agreement (6.08, 7.15, and 8.66 hours). 3D reconstruction of NP distributions with confocal microscopy identifies aggregates within the medullary canal. Intermittent NP deposition continues randomly over the two week period demonstrating prolonged NP mobility in vivo. NPs are still retained at the hair bulb after 14 days. The observations further account for the excretory mechanisms of NPs and their behavior in the pilosebacous unit, and demonstrate monitoring pharmacokinetic behavior in individual animals.
Cutaneous lymphatic malformations in disappearing bone (Gorham-Stout) disease: A novel clue to the pathogenesis of a rare syndrome
Authors: Daniela Bruch-Gerharz, Claus-Dieter Gerharz, Helger Stege, Jean Krutmann, Michael Pohl, Rainer Koester, Thomas Ruzicka
Journal: Journal of the American Academy of Dermatology (2006)
Abstract 444: Hypoxia modulates EWS-FLI1 transcriptional signature and enhances invasiveness and anchorage-independent growth of Ewing's sarcoma cells <i>in-vitro</i>
Authors: Dave N. T Aryee, Stephan Niedan, Maximilian Kauer, Karin Muehlbacher, Robert L. Walker, Paul Meltzer, Christopher Poremba, Reinhard Kofler, Heinrich Kovar
Journal: Cancer Research (2010)

Abstract Hypoxia is an important factor in the tumor cell microenvironment and approximately 1-1.5% of the genome is transcriptionally responsive to hypoxia. Hypoxia-inducible factor-1 (HIF-1) is the major mediator of transcriptional activation under hypoxia. Tumor hypoxia is associated with a more aggressive phenotype of many cancers in adults, but data on pediatric tumors are scarce. By immunohistochemistry, HIF-1α expression was readily detectable in 18/28 primary Ewing′s sarcoma family tumors (ESFT), a group of highly malignant bone-associated tumors in children and young adults, hence we studied the effect of hypoxia on ESFT cell lines in-vitro. Intriguingly, we found that EWS-FLI1 protein expression, which characterizes ESFT, is transiently up-regulated by hypoxia in a HIF-1α-dependent manner. Hypoxia modulated the EWS-FLI1 transcriptional signature relative to normoxic conditions. Both synergistic as well as antagonistic transcriptional effects of EWS-FLI1 and of hypoxia were observed. Consistent with alterations in the expression of metastasis related genes, hypoxia stimulated the invasiveness and soft-agar colony formation of ESFT cells in-vitro. Our data represents the first transcriptome analysis of hypoxic ESFT cells and identifies hypoxia as an important microenvironmental factor modulating EWS-FLI1 expression and target gene activity that may impact the malignant properties of ESFT. This study was funded by: “European Embryonal Tumor Pipeline” 6th framework program of the European Commission (STREP “E.E.T. Pipeline” contract LSHC-CT-2006-037260) and grant 12675 from the Austrian National Bank Jubilaeumsfonds. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 444.
Glutathione redox cycle protects cultured endothelial cells against lysis by extracellularly generated hydrogen peroxide.
Authors: J M Harlan, J D Levine, K S Callahan, B R Schwartz, L A Harker
Journal: Journal of Clinical Investigation (1984)

We have examined the role of the glutathione redox cycle as an antioxidant defense mechanism in cultured bovine and human endothelial cells by disrupting the glutathione redox cycle at several points. Endothelial glutathione reductase was selectively inhibited with 1,3-bis(chloroethyl)-1-nitrosourea (BCNU). Cellular stores of reduced glutathione were depleted by reaction with diethylmaleate (DEM) or 1-chloro-2,4-dinitrobenzene (CDNB) or by inhibition of glutathione synthesis with buthionine sulfoximine (BSO). Whereas several strains of untreated bovine and human endothelial cells were resistant to lysis by enzymatically generated hydrogen peroxide, BCNU-treated cells were readily lysed in a time- and dose-dependent manner. Glucose-glucose oxidase-mediated lysis of BCNU-treated bovine endothelial cells was catalase-inhibitable and directly related to BCNU concentration and endogenous glutathione reductase activity. Pretreatment of bovine endothelial cells with BCNU did not potentiate lysis by distilled water, calcium ionophore, lipopolysaccharide, or hypochlorous acid. Depletion of cellular reduced glutathione by reaction with DEM or CDNB or by inhibition of glutathione synthesis by BSO also potentiated endothelial lysis by enzymatically generated hydrogen peroxide. Inhibition of endothelial glutathione reductase by BCNU or depletion of reduced glutathione by BSO increased endothelial susceptibility to lysis by hydrogen peroxide generated by phorbol myristate acetate-activated neutrophils. We conclude that the glutathione redox cycle plays an important role as an endogenous antioxidant defense mechanism in cultured endothelial cells.
Reporting of Patient-Reported Outcomes in Randomized Trials
Authors: Melanie Calvert, Jane Blazeby, Douglas G. Altman, Dennis A. Revicki, David Moher, Michael D. Brundage, for the CONSORT PRO Group
Journal: JAMA (2013)

The CONSORT (Consolidated Standards of Reporting Trials) Statement aims to improve the reporting of randomized controlled trials (RCTs); however, it lacks guidance on the reporting of patient-reported outcomes (PROs), which are often inadequately reported in trials, thus limiting the value of these data. In this article, we describe the development of the CONSORT PRO extension based on the methodological framework for guideline development proposed by the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network. Five CONSORT PRO checklist items are recommended for RCTs in which PROs are primary or important secondary end points. These recommendations urge that the PROs be identified as a primary or secondary outcome in the abstract, that a description of the hypothesis of the PROs and relevant domains be provided (ie, if a multidimensional PRO tool has been used), that evidence of the PRO instrument's validity and reliability be provided or cited, that the statistical approaches for dealing with missing data be explicitly stated, and that PRO–specific limitations of study findings and generalizability of results to other populations and clinical practice be discussed. Examples and an updated CONSORT flow diagram with PRO items are provided. It is recommended that the CONSORT PRO guidance supplement the standard CONSORT guidelines for reporting RCTs with PROs as primary or secondary outcomes. Improved reporting of PRO data should facilitate robust interpretation of the results from RCTs and inform patient care.
Effect of Dialysis Dose and Membrane Flux in Maintenance Hemodialysis
Authors: Garabed Eknoyan, Gerald J. Beck, Alfred K. Cheung, John T. Daugirdas, Tom Greene, John W. Kusek, Michael Allon, James Bailey, James A. Delmez, Thomas A. Depner, Johanna T. Dwyer, Andrew S. Levey, Nathan W. Levin, Edgar Milford, Daniel B. Ornt, Michael V. Rocco, Gerald Schulman, Steve J. Schwab, Brendan P. Teehan, Robert Toto
Journal: New England Journal of Medicine (2002)

The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain.We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer.In the standard-dose group, the mean (+/-SD) urea-reduction ratio was 66.3+/-2.5 percent, the single-pool Kt/V was 1.32+/-0.09, and the equilibrated Kt/V was 1.16+/-0.08; in the high-dose group, the values were 75.2+/-2.5 percent, 1.71+/-0.11, and 1.53+/-0.09, respectively. Flux, estimated on the basis of beta2-microglobulin clearance, was 3+/-7 ml per minute in the low-flux group and 34+/-11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as compared with the standard-dose group was 0.96 (95 percent confidence interval, 0.84 to 1.10; P=0.53), and the relative risk of death in the high-flux group as compared with the low-flux group was 0.92 (95 percent confidence interval, 0.81 to 1.05; P=0.23). The main secondary outcomes (first hospitalization for cardiac causes or death from any cause, first hospitalization for infection or death from any cause, first 15 percent decrease in the serum albumin level or death from any cause, and all hospitalizations not related to vascular access) also did not differ significantly between either the dose groups or the flux groups. Possible benefits of the dose or flux interventions were suggested in two of seven prespecified subgroups of patients.Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane.
EFFECTS OF OFFICE-BASED CAROTID ULTRASOUND ON HEALTH-RELATED BEHAVIORS AND PERCEPTIONS OF CARDIOVASCULAR DISEASE RISK IN PATIENTS
Authors: Heather Johnson, Terry L. Turke, Mark Grossklaus, Tara Dall, Sanford Carimi, Laura M. Koenig, Susan E. Aeschlimann, Claudia E. Korcarz, James H. Stein
Journal: Journal of the American College of Cardiology (2010)
Estrogens and Risk of Breast Cancer
Authors: Henry M. Lemon
Journal: JAMA (1987)

<h3>To the Editor.—</h3> We wish to urge caution in accepting the conclusion of Wingo et al<sup>1</sup>that estrogen replacement therapy does not increase the risk of breast cancer in postmenopausal women. Only 114 of the 942 cancer cases and 154 of 1117 controls had used estrogen for over ten years. Only 48 (2%) of the 2059 women had stopped using estrogen more than ten years ago. We question whether this duration of follow-up during and after estrogen therapy is long enough to justify their conclusion. The latent period between initial estrogen exposure and the appearance of breast cancer is at least 15 years for nulliparous women, as deduced from the interval between onset of menses and the initial rise in breast cancer incidence in countries throughout the world.<sup>2</sup>In pregnant women, large doses of diethylstilbestrol did not induce a significant increase in breast cancer incidence until more than
History reveals the cause of rectal bleeding
Authors: C Messidoro, L Berk, A P Rietveld
Journal: Gut (2009)

A 32-year-old man presented at our outpatient’s clinic with painless rectal bleeding and abdominal discomfort of several years duration. The blood was coloured red and mixed with the stool. His medical history revealed a scoliosis correction, appendectomy, hypertrophy and varicose veins of the right leg. The right leg was surgically corrected for its excessive length. Physical examination of the heart, lungs and abdomen …
Course and prognosis of sarcoidosis in African-Americans<i>versus</i>Caucasians
Authors: J.M. Reich
Journal: European Respiratory Journal (2001)

Course and prognosis of sarcoidosis in African-Americans versus CaucasiansTo the Editor:In support of their belief that sarcoidosis mortality is higher in African-Americans than Caucasians, LUISETTI et al.[1] cited the GIDEON and MANNINO study [2] which reported a US sarcoidosis mortality ratio, African-American: Caucasian, of 14:1.The incidence rate ratio [3] has been estimated at 13:1.Thus, the differential mortality is attributable to a difference in case rate, not to a difference in case-fatality rate.Regarding differences in ethnic severity: REISNER [4] reported that, in a New York City health clinic in which 79% of the patients with intrathoracic sarcoidosis were African-American, they constituted only 66% of those experiencing an adverse course (defined as radiographic or clinical deterioration).We found no discernible difference in outcome by stage between African-Americans and Caucasians in a US health maintenance organization [5].In summary, the proposition that African-Americans with sarcoidosis experience a more unfavourable outcome than do Caucasians is open to question.
Dietary intakes, resting metabolic rates, and body composition in benign and malignant gastrointestinal disease.
Authors: M Burke, E I Bryson, A E Kark
Journal: BMJ (1980)

Dietary protein and energy intakes were assessed in 42 patients with cancer and 24 with benign conditions of the gastrointestinal tract. The relations of dietary intake to body composition was examined. Resulting metabolic rate was measured in 51 patients. No significant differences in dietary intake or metabolic rate were found between patients with cancer and those with benign disease. There were significant positive correlations between protein and energy intakes and the ratio of total body potassium to total body water in patients with benign disease but not in those with cancer. Weight loss was probably due to inadequate food intake, the main defect being energy deficiency, since protein intake was usually well maintained. Supplementing with energy the voluntary ingested diet of patients with cancer would probably prevent weight loss in most cases.
Case 12-1978
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Barry W. Levine, Eugene J. Mark
Journal: New England Journal of Medicine (1978)

Presentation of Case First admission. A 67-year-old woman was admitted to the hospital because of Wegener's granulomatosis.She was well until three and a half months earlier, when she began to have pleuritic pain, malaise, anorexia and a sensation of fullness in the area of the paranasal sinuses. A physician prescribed tetracycline and codeine, without improvement. One month later she began to complain of "shooting pains" on both sides of the abdomen. She came to the hospital, where examination disclosed no abnormality except that the temperature was 37.8°C. X-ray films of the chest (Fig. 1) showed an irregular apical . . .
Effect of peginterferon alfa-2a on liver histology in chronic hepatitis C: A meta-analysis of individual patient data
Authors: Calogero Cammà, Danilo Di Bona, Filippo Schepis, Jenny E. Heathcote, Stefan Zeuzem, Paul J. Pockros, Patrick Marcellin, Luis Balart, Alfredo Alberti, Antonio Craxì
Journal: Hepatology (2004)

Multicenter randomized trials have shown that once-weekly pegylated interferon (peginterferon) alfa-2a is more efficacious than conventional interferon alfa-2a (IFN) in patients with chronic hepatitis C. We performed a meta-analysis of 1,013 previously untreated patients (from 3 randomized trials) with pretreatment and post-treatment liver biopsies to assess the differences between peginterferon alfa-2a and IFN in terms of their effects on liver histology. Reported values were standardized mean differences (SMD) between patients receiving peginterferon alfa-2a and those receiving IFN (post-treatment value minus baseline value for each group). We used a random-effects model to quantify the average effect of peginterferon alfa-2a on liver histology. Peginterferon alfa-2a significantly reduced fibrosis compared with IFN (SMD, −0.14; 95% CI: −0.27, −0.01; P = .04). A reduction in fibrosis was observed among sustained virologic responders (SMD, −0.59; 95% CI: −0.89, −0.30; P &lt; .0001) and patients with recurrent disease (SMD, −0.34; 95% CI: −0.54, −0.14; P = .0007), whereas no significant reduction was observed among nonresponders (SMD, −0.13; 95% CI: −0.32, 0.05; P = .15). Logistic regression analysis indicated that patients with sustained virologic responses (SVRs) had an odds ratio (OR) of 1.61 (95% CI: 1.14, 2.29) for reduction in fibrosis compared with patients without SVRs, whereas obese patients (body mass index [BMI] &gt; 30 kg/m 2 ) had an OR of 0.56 (95% CI: 0.35, 0.90) compared with normal-weight (BMI &lt; 25 kg/m 2 ) and overweight patients (BMI, 25-30 kg/m 2 ). In conclusion, in patients with chronic hepatitis C with or without cirrhosis, peginterferon alfa-2a (relative to IFN) significantly reduced fibrosis. The beneficial effects of peginterferon on liver histology are closely related to virologic response. (Hepatology 2004;39:333-342.)
Travel to a conference (obtaining funding).
Authors: K. C. Tan, D. J. Betteridge
Journal: BMJ (1989)

<h3>AIMS</h3> To determine the most suitable anthropometric and impedance measures and current frequency for the application of bioelectrical impedance to neonates receiving intensive care; and to derive predictive models for the estimation of total body water. <h3>METHODS</h3> Twenty eight babies (median gestational age 30.5 weeks, range 24–38; median birthweight 1.388 kg, range 0.690–3.510) were each studied once during the first week after birth. Total body water was first measured by the method of dilution of isotopic water (H<sub>2</sub><sup>18</sup>O). Bioelectrical measurements were made using the tetrapolar surface electrode method from four main distal limb positions (right hand–right foot; right hand–left foot; left hand–left foot; left hand–right foot), the left upper arm–left thigh position and the left scapula–right buttock position, and using six frequencies ((500, 250, 100, 50, 10 and 5 kHz). Regression models, to predict total body water, which were both independent and dependent of body weight on the day of study, were derived. <h3>RESULTS</h3> Resistance readings at 50 kHz obtained from the distal limb positions performed best. There was no difference between the distal limb positions. There was no difference in the goodness of fit of the models when using each of three indices of conductor length, foot, spine and sternum. The model total body water (litres) (TBW) = 0.016 + 0.674 bodyweight(kg)−0.038 wt<sup>2</sup> + 3.84 foot length (cm)<sup>2</sup>/resistance (50 kHz in OHMS) performed best, accounting for 99.5% of the variation in TBW, with a 95% prediction interval of 165 ml. The model TBW = 0.144 + 15.518 foot length (cm)<sup>2</sup>/resistance (50 kHz in ohms) accounted for 96.4% of the variation and had a 95% prediction interval of 420 ml. <h3>CONCLUSIONS</h3> Bioelectrical impedance analysis is a simple, non-invasive method of estimating total body water in neonates receiving intensive care. It can be applied to both the assessment of changes in body water and body composition.
The tryptophan catabolite l-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function
Authors: Mariella Della Chiesa, Simona Carlomagno, Guido Frumento, Mirna Balsamo, Claudia Cantoni, Romana Conte, Lorenzo Moretta, Alessandro Moretta, Massimo Vitale
Journal: Blood (2006)
Death notices are often dull catalogues of success
Authors: A. Dally
Journal: BMJ (1995)

EDITOR,—The quality of medical practice is threatened by Liz Crossan and Richard Smith's thoughts on obituaries1 and diminished by the Lancet's decision to abolish obituaries. Instead of developing ideas about “publishing death notices rather than obituaries,” the BMJ should be increasing the number of obituaries and making them interesting to read. The medical profession understands itself through its history. Obituaries are important in this. Current …
"MATERNITY WARDS IN GENERAL HOSPITALS": REPLY TO DRS. SKEEL AND RUNNELS
Authors: J. B. DeLee
Journal: JAMA (1933)

To the Editor:  —I am gratified to learn that the Cleveland Hospital Obstetric Society (The Journal, February 25, p. 597) agrees with me on the main issue: Actual physical separation and entirely separate personnel are essential to safety. Isolated separate labor and delivery rooms are necessary. The laundry of the maternity division should never be mixed with that of the medical and surgical floors, so that sheets, pillow cases, and the like that have been used by infected surgical patients cannot be sent from the laundry to the obstetric floor. No hospital has the moral right, and none should have the legal right, to accept cases for delivery without making physical and administrative preparation for their safe care. What more do  ask than this perfect separation? I will concede that if the maternity ward of the general hospital were on a completely separated floor and that if the doctors,
Locating and Appraising Systematic Reviews
Authors: Dereck L. Hunt
Journal: Annals of Internal Medicine (1997)

In this article, we describe the strengths and weaknesses of several methods of locating systematic reviews, including electronic databases such as MEDLINE, Best Evidence (the electronic version of ACP Journal Club and Evidence-Based Medicine), and the Cochrane Library (a regularly updated source of reviews and controlled trials produced by the Cochrane Collaboration). We also present steps that can be used to critically appraise review articles; as an example, we use a systematic review that evaluates the gastrointestinal toxicity of various nonsteroidal anti-inflammatory drugs in the context of a clinical scenario.