tbuckley/cabot-search huggingface dataset:
Long-Term Effects of Sildenafil in a Rat Model of Chronic Mitral Regurgitation
Authors: Kyung-Hee Kim, Yong-Jin Kim, Jung-Hun Ohn, Jimin Yang, Sang-Eun Lee, Sae-Won Lee, Hyung-Kwan Kim, Jeong-Wook Seo, Dae-Won Sohn
Journal: Circulation (2012)

We tested the hypothesis that chronic treatment with sildenafil attenuates left ventricular (LV) remodeling and prevents exercise intolerance in chronic mitral regurgitation (MR).MR was created in Sprague-Dawley rats by making a hole on the mitral leaflet. Two weeks after MR creation, MR and LV dilatation were confirmed by echocardiography, and rats were randomly assigned to sildenafil treatment (MR+sildenafil group; 50 mg/kg PO twice a day; n=16) or normal saline only (MR group; n=16) and continued for 4 months. Sixteen sham rats were compared with MR rats. After 4 months, LV size was smaller in the MR+sildenafil compared with the MR group (LV end-systolic dimension, 4.7±0.3 for sham versus 5.9±0.3 for MR+sildenafil versus 7.4±0.5 mm for MR; P<0.05; LV end-diastolic dimension, 8.3±0.4 versus 10.5±0.2 versus 11.7±0.61 mm, respectively; P<0.05). LV ejection fraction was greater in the MR+sildenafil group than in the MR group (70.2±2.2 for sham versus 67.0±4.2 for MR+sildenafil versus 58.9±2.5 for MR; P=0.01). Serial treadmill test revealed that exercise capacity was reduced in the MR but not in the MR+sildenafil group. Transcriptional profiling of cardiac apical tissues revealed that gene sets related to inflammatory response, DNA damage response, cell cycle checkpoint, and cellular signaling pathways were significantly enriched by genes with reciprocal changes. Pathological analysis showed that perivascular fibrosis was more prominent in the MR than in the MR+sildenafil group and that the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells was 2-fold greater in the MR compared with the MR+sildenafil group.Sildenafil significantly attenuates LV remodeling and prevents exercise intolerance in a rat model of chronic MR. This benefit may be associated with the antiapoptotic, anti-inflammatory effects of sildenafil.
CIVIL SERVICE REFORM IN STATE INSTITUTIONS—REORGANIZATION OF THE MEDICAL STAFF.
Authors: BOERNE BETTMAN
Journal: JAMA (1895)

All measures toward reform in the treatment of the insane will prove an utter failure until the manner of appointing the medical staff is radically changed. The superintendent and head of the institution must possess not only the requisite medical skill to fit him for the care and supervision of the patients intrusted to him, but he must also be endowed with executive abilities to maintain a business-like organization and to exact well-disciplined service from a large<i>personnel</i>. Burdened as he is by multitudinous duties, he naturally is obliged to delegate the treatment to the medical assistants. To them is intrusted the diagnosis of the mental complaint and its subsequent treatment. Upon them rest great responsibilities. Medical assistants are ordinarily appointed through political or other influences. The superintendent is often not consulted in the matter, but is forced to submit to the dictates of others, whose only concern it is
Endoscopic Monitoring of the Gastric Lesser Curve Following Proximal Gastric Vagotomy
Authors: R. Kirk, R. Foley
Journal: Endoscopy (1979)

The lesser curve gastric mucosa was examined endoscopically in 60 patients, 3 to 6 days after performing proximal gastric vagotomy. Minor and equivocal changes were seen in only 3 patients. Three patients had adjunctive splenectomy but did not show any evidence of mucosal vascular insufficiency in the proximal stomach. Our findings do not confirm a report from other investigators of lesser curve gastric ulceration attributed to partial ischaemia short of lesser curve necrosis. Endoscopy should be considered in patients developing unexplained features following proximal gastric vagotomy.
A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons
Authors: Dawei Zhang, Mari Pekkanen-Mattila, Mansoureh Shahsavani, Anna Falk, Ana I. Teixeira, Anna Herland
Journal: Biomaterials (2013)

The recent progress in stem cell techniques has broadened the horizon for in vitro disease modeling. For desired in vivo like phenotypes, not only correct cell type specification will be critical, the microenvironmental context will be essential to achieve relevant responses. We demonstrate how a three dimensional (3D) culture of stem cell derived neurons can induce in vivo like responses related to Alzheimer's disease, not recapitulated with conventional 2D cultures. To acquire a neural population of cells we differentiated neurons from neuroepithelial stem cells, derived from induced pluripotent stem cells. p21-activated kinase mediated sensing of Aβ oligomers was only possible in the 3D environment. Further, the 3D phenotype showed clear effects on F-actin associated proteins, connected to the disease processes. We propose that the 3D in vitro model has higher resemblance to the AD pathology than conventional 2D cultures and could be used in further studies of the disease.
Short-term Quality-of-Life Outcomes Following Laparoscopic-Assisted Colectomy vs Open Colectomy for Colon Cancer&lt;SUBTITLE&gt;A Randomized Trial&lt;/SUBTITLE&gt;
Authors: Jane C. Weeks, Heidi Nelson, Shari Gelber, Daniel Sargent, Georgene Schroeder
Journal: JAMA (2002)

Laparoscopic-assisted colectomy (LAC) has emerged as the preferred minimally invasive surgical strategy for diseases of the colon. The safety and efficacy of LAC for colon cancer are unknown, and the nature and magnitude of any quality-of-life (QOL) benefit resulting from LAC for colon cancer is also unknown.To compare short-term QOL outcomes after LAC vs open colectomy for colon cancer.Multicenter, randomized controlled trial (Clinical Outcomes of Surgical Therapy [COST]). Between September 1994 and February 1999, 37 of 48 centers provided data for the QOL component of the trial for 449 consecutive patients with clinically resectable colon cancer.Scores on the Symptoms Distress Scale (SDS), Quality of Life Index, and a single-item global rating scale at 2 days, 2 weeks, and 2 months postoperative; duration of postoperative in-hospital analgesic use; and length of stay.Of 449 patients, 428 provided QOL data. In an intention-to-treat analysis comparing SDS pain intensity, SDS summary, QOL Index summary, and global rating scale scores at each time point, the only statistically significant difference observed between groups was the global rating scale score for 2 weeks postsurgery. The mean (median) global rating scale scores for 2 weeks postsurgery were 76.9 (80) for LAC vs 74.4 (75) for open colectomy (P =.009). While in the hospital, patients assigned to LAC required fewer days of both parenteral analgesics compared with patients assigned to open colectomy (mean [median], 3.2 [3] vs 4.0 [4] days; P<.001) and oral analgesics (mean [median], 1.9 [1] vs 2.2 [2] days; P =.03).Only minimal short-term QOL benefits were found with LAC for colon cancer compared with standard open colectomy. Until ongoing trials establish that LAC is as effective as open colectomy in preventing recurrence and death from colon cancer, this procedure should not be offered to patients with colon cancer.
When i use a word . . .: Sloe gin
Authors: J. Aronson
Journal: BMJ (1997)

Last autumn I went down to the banks of the Cherwell looking for blackthorn bushes (Prunusspinosa) to pick sloes with which to make that nectar of homemade liqueurs, sloe gin. I had already looked up the recipe in The Alice B Toklas Cook Book , actually wanting an excuse to reread Brian Gysen's notorious recipe for hashish fudge, which includes a pulverised bunch of “canibus sativa” (obtaining which “may present certain difficulties”). The fudge, we are told, “should …
Degradation of canine cardiac myosin and actin by cathepsin D isolated from homologous tissue
Authors: E. A. OGUNRO, R. B. LANMAN, J. R. SPENCER, A. G. FERGUSON, M. LESCH
Journal: Cardiovascular Research (1979)

The ability of canine cardiac cathepsin D to catalyse hydrolysis of myosin and actin isolated from homologous tissue was monitored using both SDS polyacrylamide gel electrophoresis and the release of trichloroacetic acid soluble radioactivity from the radioactively (14C) labelled proteins. Cathepsin D readily catalysed the hydrolysis of myosin and actin. The pH-activity profile for myosin hydrolysis exhibited two optima with a major peak at pH 2.6 together with a smaller peak at pH 3.4. This was distinct from the pH-activity profile for actin hydrolysis where a single optimum at pH 4.2 was observed. Incubation of cathepsin D with myosin (pH 2.6, 37°C) resulted in complete degradation of myosin light chains (MW =28000±700 and 18600±350, n=4) within 10 min while heavy chains (MW= 190400±2500, n=4) were degraded into three proteins of molecular weight 32000 ±750; 37000 ±1000 and 49000 ±750 (n=4) within 4 h. Further incubation (24 h) of cathepsin D with myosin resulted in two proteins of MW 29000±2000 and 48800±3100 (n=4). In the case of actin (MW 44800± 1600, n=6) polypeptides produced as a result of hydrolytic cleavage by cathepsin D (pH 4.2, 37°C) were not observed on SDS gels, although the overall size of the actin band was markedly decreased at 24 h. Cathepsin D catalysed the hydrolysis of myosin at near neutral pH (6.5) although the overall rate of degradation was considerably reduced compared to that observed at pH 2.6. Pepstatin A was a potent inhibitor of the hydrolysis of myosin and actin at all pH values investigated indicating that cathepsin D and not a contaminant was responsible for the observed degradation.
Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses
Authors: Giulia Nizzoli, Jana Krietsch, Anja Weick, Svenja Steinfelder, Federica Facciotti, Paola Gruarin, Annalisa Bianco, Bodo Steckel, Monica Moro, Mariacristina Crosti, Chiara Romagnani, Katharina Stölzel, Sara Torretta, Lorenzo Pignataro, Carmen Scheibenbogen, Petra Neddermann, Raffaele De Francesco, Sergio Abrignani, Jens Geginat
Journal: Blood (2013)
Effects of Exercise Amount and Intensity on Abdominal Obesity and Glucose Tolerance in Obese Adults
Authors: Robert Ross, Robert Hudson, Paula J. Stotz, Miu Lam
Journal: Annals of Internal Medicine (2015)

Exercise reduces obesity and related glucose tolerance, but whether increasing exercise intensity offers additional benefit at fixed exercise amounts is unknown.To determine the separate effects of exercise amount and intensity on abdominal obesity and glucose tolerance.24-week, single-center, parallel-group trial from 2009 to 2013. (ClinicalTrials.gov: NCT00955071).Kingston, Ontario, Canada.300 abdominally obese adults.Control (no exercise) (n = 75) or 5 weekly sessions of low-amount, low-intensity exercise (LALI) (180 and 300 kcal/session for women and men, respectively, at 50% of maximum oxygen consumption [V̇o2peak]) (n = 73); high-amount, low-intensity exercise (HALI) (360 and 600 kcal/session, respectively, at 50% of V̇o2peak) (n = 76); or high-amount, high-intensity exercise (HAHI) (360 and 600 kcal/session, respectively, at 75% of V̇o2peak) (n = 76). Daily unsupervised physical activity and sedentary time were measured by accelerometer.Waist circumference and 2-hour glucose level (primary outcomes) and cardiorespiratory fitness and measures of insulin action (secondary measurements).217 participants (72.3%) completed the intervention. Mean exercise time in minutes per session was 31 (SD, 4.4) for LALI, 58 (SD, 7.6) for HALI, and 40 (SD, 6.2) for HAHI. Daily unsupervised physical activity and sedentary time did not change in any exercise group versus control (P > 0.33). After adjustment for age and sex in a linear mixed model, reductions in waist circumference were greater in the LALI (-3.9 cm [95% CI, -5.6 to -2.3 cm]; P < 0.001), HALI (-4.6 cm [CI, -6.2 to -3.0 cm]; P < 0.001), and HAHI (-4.6 cm [CI, -6.3 to -2.9 cm]; P < 0.001) groups than the control group but did not differ among the exercise groups (P > 0.43). After adjustment for covariates, reductions in 2-hour glucose level were greater in the HAHI group (-0.7 mmol/L [-12.5 mg/dL] [CI, -1.3 to -0.1 mmol/L {-23.5 to -1.5 mg/dL}]; P = 0.027) than the control group but did not differ for the LALI or HALI group versus the control group (P > 0.159). Weight loss was greater in all exercise groups than the control group (P < 0.001); however, reduction in body weight did not differ among the exercise groups (P > 0.182).The clinical importance of reducing 2-hour glucose level in nondiabetic adults remains undetermined.Fixed amounts of exercise independent of exercise intensity resulted in similar reductions in abdominal obesity. Reduction in 2-hour glucose level was restricted to high-intensity exercise.
Predictors of Achievement in Academic Medicine
Authors: Mindy Thompson Fullilove
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The authors of the recent article "Early Predictors of Career Achievement in Academic Medicine"<sup>1</sup>urged selection and funding committees to examine three means to enhance the nation's yield of successful clinician-investigators: "scholastic performance in medical school (including membership in AOA [Alpha Omega Alphal]), research experience in medical school, and the number of early publications in making recommendations and decisions." While these suggestions appear perfectly reasonable, we are concerned that these conclusions, drawn from an all-male, predominantly white sample, might, in fact, harm our efforts to increase the representation of women and students of color in academic medicine. We are not convinced that this study is adequate to describe the path to academic success for nonmale, nonwhite students. The authors are careful to note that their sample is drawn from male graduates of a single medical school. The racial composition of their sample is not described, but
Theophylline accelerates human granulocyte apoptosis not via phosphodiesterase inhibition.
Authors: K Yasui, B Hu, T Nakazawa, K Agematsu, A Komiyama
Journal: Journal of Clinical Investigation (1997)

Theophylline, in addition to its bronchodilator effect, is reported to have an antiinflammatory action that may account for its clinical effectiveness in the reduction of inflammatory cells in the airway. In bronchial asthma, such inflammatory cytokines as GM-CSF and IL-5 are upregulated and have been proposed to cause granulocyte infiltration (neutrophils and eosinophils) in the airway by inhibition of granulocyte apoptosis. We examined the abilities of theophylline to counteract the prolongation of human granulocyte survival caused by cytokines. Theophylline was shown to shorten granulocyte survival in a dose-dependent manner. Upon incubation with a therapeutical concentration of theophylline (0.1 mM; 18 microg/ml), percentages of GM-CSF (10 ng/ml)-induced delayed apoptosis increased from 18+/-2% to 38+/-3% (p < 0.02) in neutrophils and from 21+/-2% to 35+/-2% (p < 0.02; 24-h incubation) in eosinophils. The percentage of IL-5 (5 ng/ml)-induced delayed eosinophil apoptosis also increased from 22+/-4% to 33+/-2% (P < 0. 05). In contrast, cyclic AMP (cAMP)-increasing agents (3-isobutylmethylxanthine, dibutyryl cAMP, and rolipram) inhibited granulocyte apoptosis in the control and anti-Fas antibody-treated cells. In eosinophils, the expression of bcl-2 protein decreased after incubation with theophylline. These findings suggest that theophylline accelerates granulocyte apoptosis, which may play an essential role in inflammation, and controls granulocyte longevity regardless of the elevation of intracellular cAMP levels.
Abstract 2145: Coupling S100A4 to Rhotekin alters Rho signaling output in breast cancer cells
Authors: Min Chen, Anne R. Bresnick, Kathleen L. O'Connor
Journal: Cancer Research (2012)

Abstract S100A4 is a calcium binding protein and tumor metastasis associated factor that has been suggested to promote motility and invasiveness of different types of cancer. This migratory promoting effect, in part, is due to the interaction of S100A4 with actin and actin binding proteins, such as myosin IIA. We found that S100A4 interacts with Rho binding domain of Rhotekin (TRBD), one of the Rho effectors, thus suggesting a connection between the Rho and S100A4 pathways. To test whether this interaction is specific, we performed GST pull-down assays using Rho binding domain from different Rho effectors such as Rhotekin, Rhophilin, PKN, ROCK II, and Citron. These results showed that S100A4 specifically interacts with Rho binding domain of Rhotekin but not of other Rho effectors. We further determined that this interaction is direct and calcium-dependant by performing GST-TRBD pull-down assays with purified S100A4 in the presence and absence of calcium. The in vivo interaction of these two proteins was further confirmed by immunoprecipitation of exogenously expressed mutated forms of Rhotekin with endogenous S100A4 from MDA-MB-231 cells. Confocal microscopy showed that Rhotekin and S100A4 co-localize at the edge of membrane ruffles in response to EGF. We demonstrated that S100A4 did not bind TRBD using the same residues as Rho, as determined by using a triple-A mutant of Rhotekin. Interestingly, we found that active Rho, S100A4 and Rhotekin are in a complex by using constitutively active GST-RhoQ63L pull-down assay. To examine the function of this interaction, RNAi was used to suppress Rhotekin and/or S100A4 in MDA-MB-231. F-actin staining showed that suppression of both RTKN and S100A4 leads to the loss of Rho-dependent membrane ruffling in response to EGF stimulation, an increase in contractile F-actin “stress” fibers in the cell body and a reduction in invasive growth in three-dimensional culture. Taken together, we showed that S100A4 specifically and directly interacts with Rhotekin in a calcium-dependent manner. This coupling permits S100A4 to complex with RhoA and switch RhoA function from stress fiber formation to membrane ruffling. Based on the function of this interaction, we propose that interaction of S100A4 and Rhotekin alters the functional output of Rho signaling to confer an invasive phenotype in breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2145. doi:1538-7445.AM2012-2145
Fatal Reactivation of Cytomegalovirus Infection after Use of Rituximab for a Post-Transplantation Lymphoproliferative Disorder
Authors: Florence Suzan, Mounia Ammor, Vincent Ribrag
Journal: New England Journal of Medicine (2001)

To the Editor: Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen expressed on most B cells and is used to treat B-cell non-Hodgkin's lymphoma.1 Recently, rituximab has b...
Compensation for Injured Research Subjects Regulation by Informed Consent
Authors: William J. Curran
Journal: New England Journal of Medicine (1979)

INFORMED consent has been examined in a number of recent "LawMedicine Notes"1 2 3 and in a commentary on randomized trials.4 These discussions have assumed that informed consent is required to protect the autonomy of human beings in making decisions about involvement in medical treatment or clinical investigations. Now, however, the Department of Health, Education, and Welfare has applied its authority to regulate the content of informed consent to accomplish a different, though related, purpose. The department has used informed consent as a vehicle to help achieve a national policy of providing nofault compensation to subjects injured in federally supported research projects. . . .
Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher's disease.
Authors: R O Brady, J N Kanfer, R M Bradley, D Shapiro
Journal: Journal of Clinical Investigation (1966)

The accumulation of abnormal quantities of glu- cocerebroside in the reticuloendothelial cells of patients with Gaucher's disease is well documented (2-7).Previous studies in this laboratory indi- cated no abnormality in cerebroside formation in spleen tissue obtained from patients with Gauch- er's disease (8).These observations suggested that the biochemical lesion in these patients might be on the pathway of cerebroside catabolism.To pursue such investigations, we chemically synthe- sized glucocerebroside-14C labeled in carbon atom 1 of the D-glucose portion of the cerebroside mole- cule (9).With this material, it was possible to demonstrate and partially purify an enzyme in human spleen tissue that catalyzes the hydrolysis of the glycosidic bond of the cerebroside molecule.The products of the reaction catalyzed by the most highly purified enzyme preparation were shown to be glucose and ceramide (N-acylsphingosine) (9).When this information became available, stud- ies were undertaken to determine the level of the glucocerebroside-cleaving enzyme in human spleen tissue obtained from patients with various condi- tions.The present report describes the results obtained in these experiments and presents evi- dence of a marked attenuation of glucocerebrosidecleaving activity in the spleen of patients with Gaucher's disease.
Endobronchial allergen challenge in asthma. Demonstration of cellular source of granulocyte macrophage colony-stimulating factor by in situ hybridization.
Authors: D H Broide, G S Firestein
Journal: Journal of Clinical Investigation (1991)

Airway inflammation is thought to play an important role in the pathogenesis of asthma. We have used in situ hybridization and an immunoassay to determine whether granulocyte macrophage colony-stimulating factor (GM-CSF) (a cytokine capable of eosinophil activation) is present in the airway of asthmatics (n = 6) who have 37.0 +/- 15.1% airway eosinophilia after endobronchial allergen challenge. Levels of immunoreactive GM-CSF (less than 4 pg/ml pre-allergen versus 180.5 +/- 46.9 pg/ml post-allergen) increased significantly 24 h after endobronchial allergen stimulation. The cellular source of bronchoalveolar lavage (BAL) GM-CSF, as determined by in situ hybridization and immunoperoxidase staining, was derived predominantly from UCHL-1 positive BAL lymphocytes, as well as from a smaller population of alveolar macrophages. Before local endobronchial allergen challenge, less than 1% of lymphocytes and alveolar macrophages recovered by BAL expressed GM-CSF mRNA, whereas after allergen stimulation 92.6 +/- 3.4% of lymphocytes and 17.5 +/- 22.7% of alveolar macrophages expressed GM-CSF mRNA. This study provides evidence that in an experimental model of allergen-induced asthma, activation of the immune and inflammatory response (BAL lymphocyte and alveolar macrophage production of GM-CSF) is temporally associated with an inflammatory cell influx of eosinophils into the airway.
Peripheral Vascular Collapse after the Subcutaneous Use of a Hypertonic Nonelectrolyte Solution
Authors: John J. Butler
Journal: New England Journal of Medicine (1953)

IT has been shown experimentally in human beings that 5 per cent and 10 per cent dextrose in distilled water given subcutaneously will produce a state of mild peripheral vascular collapse.1 Danowski, Winkler and Peters2 have commented on an unpublished experiment in which an infusion of 5 per cent glucose in distilled water given subcutaneously had "effects on the plasma volume and circulatory dynamics identical with those of salt depletion shock." A recent editorial3 reviewed these experimental observations, and warned of "the possible dangers that might be encountered when large volumes of sugar containing, or amino acid containing solutions are . . .
Inflammation-associated lysophospholipids as ligands for CD1d-restricted T cells in human cancer
Authors: David H. Chang, Haiteng Deng, Phillip Matthews, Joseph Krasovsky, Govind Ragupathi, Radek Spisek, Amitabha Mazumder, David H. Vesole, Sundar Jagannath, Madhav V. Dhodapkar
Journal: Blood (2008)