tbuckley/cabot-search huggingface dataset:
PATHOLOGY OF THE EXPERIMENTAL PNEUMONIAS IN MICE FOLLOWING INHALATION OF STREPTOCOCCUS HÆMOLYTICUS, OF FRIEDLÄNDER'S BACILLUS, AND OF PNEUMOCOCCUS
Authors: Arnold Branch, Ernest G. Stillman
Journal: The Journal of Experimental Medicine (1925)

1. Pulmonary consolidation may be produced in normal mice by the inhalation of Friedländer's bacillus or Streptococcus haemolylicus. 2. The initial lesion is in both instances interstitial in character and the spread is by way of the interstitial tissue, though the ultimate consolidation may come to resemble in the gross a lobar pneumonia. 3. The lesions grossly and microscopically may be distinguished from the lobar consolidation associated with pneumococcus infection of the lung. 4. Friedländer's bacillus and Streptococcus haemolyticus give rise to pneumonia in mice previously normal, whereas the pneumococcus produces pulmonary lesions only under special circumstances, as when the animals are alcoholized after partial immunization.
Patients must be told that treatment will be randomised
Authors: J. Gilbert
Journal: BMJ (1995)

Evaluation of palliative careRecruitment figures may be low EDrroR,-In response to the paper by Ian R McWhinney and colleagues' we wish to report our experience of recruitment into trials in the palliative care setting.The trials were not of a palliative care service but of palliative therapeutic interventions in a specialist cancer hospital.These included randomised studies of pharmacological and non-pharmacological strategies in the manage- ment of bowel obstruction, hypercalcaemia, nausea induced by opiates, anorexia, pain, and dyspnoea as well as non-randomised studies in patients in pain.In the 12 months to October 1994, 344 patients were referred to one of two research sisters in palliative care as being suitable for entry to one of the above studies.Both inpatients and outpatients were referred by medical and nursing staff throughout the hospital.Of the 344 patients, 109 were not approached as they did not fulfil the criteria for inclusion in the studies.Thus after full discussion regarding the implications of entering the trial 235 patients were asked if they would agree to participate in one of the studies.Only 142 patients gave informed consent.The remainder were not entered into the studies because they were too unwell or their condition had deteriorated (27), they were eligible but declined to consent (38), they lived too far away from the hospital ( 16), or for unknown reasons (12).Thus 41% of the patients initially referred and 60% of the patients who were approached were entered into studies.These figures are low but are likely to be higher than those achieved in other palliative care settings since the patients were recruited in a specialist cancer hospital with a high research profile, where the role of the research sister is well established.We agree with Henry McQuay and Andrew Moore that palliative care should not be excused from conducting randomised controlled trials simply because they are difficult to do,2 but our recruitment data show several of the inherent difficulties.
Role of autacoids in cardiovascular collapse in anaphylactic shock in anesthetized dogs
Authors: S Mink
Journal: Cardiovascular Research (1999)

Objective: In anaphylactic shock (AS), the relative effects of the autacoids including histamine, prostaglandins (prost), and leukotrienes (leuk) on causing cardiovascular collapse and the extent to which receptor blocking agents and pathway inhibitors may prevent this collapse are not clear. Methods: In randomized design, we investigated whether blockade of histamine H1, H2, and H3 receptors or inhibition of the cyclooxygenase (cyclo) and lipoxygenase pathways (lipox) prevented AS in ragweed sensitized dogs. Seven dogs were studied under pentobarbital anesthesia in which the treatment studies were approximately 2 weeks apart. Results: During H1 receptor blockade, the decreases in blood pressure and cardiac output otherwise observed in AS were attenuated (P<0.05) and the release of prost, thromboxanes, and leuk were reduced as compared with nontreatment studies. Cyclo inhibition also attenuated cardiovascular collapse and mediator release in AS, but the other treatments showed no effects. Conclusion: H1 receptor blockade and cyclo may attenuate cardiovascular shock in AS. These agents inhibit autacoid release from mast cells in addition to any specific receptor blocking and pathway inhibition effects.
Updated and Revised Diabetes Family Conflict Scale
Authors: Korey K. Hood, Deborah A. Butler, Barbara J. Anderson, Lori M.B. Laffel
Journal: Diabetes Care (2007)

OBJECTIVE— The purpose of this study was to update the Diabetes Family Conflict Scale (DFCS) in the era of intensive diabetes management and provide an indication of its psychometric properties. RESEARCH DESIGN AND METHODS— The revised DFCS and measures of negative emotions around blood glucose monitoring (BGM), quality of life, and perceived parental burden from diabetes management were completed by 202 children and adolescents with type 1 diabetes and their primary caregivers. Insulin regimen, adherence, and glycemic control were also assessed. RESULTS— The revised DFCS demonstrated strong psychometric properties. There was acceptable internal consistency for child and caregiver forms of the DFCS. Factor analysis revealed two factors related to direct and indirect management tasks. Both child (r = 0.27, P &amp;lt; 0.01) and caregiver (r = 0.26, P &amp;lt; 0.01) DFCS scores were correlated with A1C values. Multivariate analysis of factors usually associated with A1C values showed an additive, independent contribution of diabetes-specific family conflict to the prediction of glycemic control: F (12,189) = 6.17, P &amp;lt; 0.01, R2 = 0.28. Conflict around direct management tasks (e.g., BGM) was a more important predictor of higher A1C levels than conflict around indirect management tasks (e.g., telling friends about diabetes). CONCLUSIONS— The revised and updated DFCS demonstrates strong psychometric properties and can be used as a tool for measuring the level of diabetes-specific conflict in families with children and adolescents with type 1 diabetes.
High prevalence of thyroid autoantibodies in a prospective series of patients with chronic hepatitis C before interferon therapy
Authors: Albert Tran, Jean François Quaranta, Sylvia Benzaken, Valerie Thiers, Hoang Trong Chau, Patrick Hastier, Daniel Regnier, Gilles Dreyfus, Christian Pradier, Jean-Louis Sadoul, Xavier Hebutern, Patrick Rampa
Journal: Hepatology (1993)

After describing two cases of Hashimoto's thyroiditis associated with chronic hepatitis C, we set up a prospective study to assess the prevalence of thyroid autoantibodies (thyroglobulin and thyroid microsomal autoantibodies) in 72 chronic hepatitis C patients (43 men and 29 women; mean age = 51 +/- 2.1 yr) before interferon therapy admitted between January and December 1991 to our liver unit. Thyroid autoantibodies were systematically assayed in 60 chronic HBsAg-positive patients (34 men and 26 women; mean age = 50 +/- 2.2 yr), who served as controls. Antibody to hepatitis C virus was detected with a second-generation enzyme immunoassay and then confirmed with a recombinant immunoblot assay and a supplemental enzyme immunoassay using two beads. In chronic hepatitis C patients, no men had thyroid autoantibodies. Nine of 29 women (31%) had thyroid autoantibodies. Among them, six (20.7%) had high titers of thyroid autoantibodies, and two had hypothyroidism. In all nine of these women, hepatitis C virus viremia was detected on nested polymerase chain reaction (with primers located in the 5' untranslated region). One year later, titers of thyroid autoantibodies had increased in one patient. Three other patients progressed to hypothyroidism. We judged four of 29 patients (13.8%) to have Hashimoto's thyroiditis on the basis of their high titers of thyroid autoantibodies and biological features of hypothyroidism. In the control group, only one man had thyroid microsome autoantibodies, at a very low titer (1:100). The association between chronic hepatitis C and presence of thyroid autoantibodies is clearly confirmed (p = 0.021) by this study.
Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis
Authors: Su Yeon Lee, Hyun Min Jeon, Cho Hee Kim, Min Kyung Ju, Hye Sun Bae, Hye Gyeong Park, Sung-Chul Lim, Song Iy Han, Ho Sung Kang
Journal: Molecular Cancer (2011)

Abstract Background In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood. Results In the present study, we show that Distal-less 2 (Dlx-2), a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS) in response to glucose deprivation (GD), one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an in vitro model of solid tumors. Dlx-2 short hairpin RNA (shRNA) inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH) release, indicating the important role(s) of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis. Conclusions These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.
Eradication of Minimal Residual Disease in B-Cell Chronic Lymphocytic Leukemia After Alemtuzumab Therapy Is Associated With Prolonged Survival
Authors: Paul Moreton, Ben Kennedy, Guy Lucas, Michael Leach, Saad M.B. Rassam, Andrew Haynes, Jane Tighe, David Oscier, Christopher Fegan, Andy Rawstron, Peter Hillmen
Journal: Journal of Clinical Oncology (2005)

To test whether eradication of minimal residual disease (MRD) in B-cell chronic lymphocytic leukemia (CLL) by alemtuzumab is associated with a prolongation of treatment-free and overall survival.Ninety-one previously treated patients with CLL (74 men and 17 women; median age, 58 years [range, 32 to 75 years]; 44 were refractory to purine analogs) received a median of 9 weeks of alemtuzumab treatment between 1996 and 2003. Regular bone marrow assessments by MRD flow cytometry were performed with the aim of eradicating detectable MRD (< 1 CLL cell in 10(5) normal cells).Responses according to National Cancer Institute-sponsored working group response criteria were complete remission (CR) in 32 patients (36%), partial remission (PR) in 17 patients (19%), and no response (NR) in 42 patients (46%). Twenty-two (50%) of 44 purine analog-refractory patients responded to alemtuzumab. Detectable CLL was eradicated from the blood and marrow in 18 patients (20%). Median survival was significantly longer in MRD-negative patients compared with those achieving an MRD-positive CR, PR, or NR. Patients achieving an MRD-negative CR had a longer treatment-free survival than patients with MRD-positive CRs, PR, or NR: MRD-negative CRs, not reached; MRD-positive CRs, 20 months; PRs, 13 months; NR, 6 months (P < .0001). Overall survival for the 18 patients with MRD-negative remissions was 84% at 60 months. Eight (47%) of the MRD-negative patients converted to MRD positivity at a median of 28 months.MRD-negative remission in CLL is achievable with alemtuzumab, leading to an improved overall and treatment-free survival.
Eliminating a Region of Respiratory Syncytial Virus Attachment Protein Allows Induction of Protective Immunity without Vaccine-enhanced Lung Eosinophilia
Authors: Tim E. Sparer, Stephen Matthews, Tracy Hussell, Aaron J. Rae, Blanca Garcia-Barreno, Jose A. Melero, Peter J.M. Openshaw
Journal: The Journal of Experimental Medicine (1998)

In a murine model of respiratory syncytial virus disease, prior sensitization to the attachment glycoprotein (G) leads to pulmonary eosinophilia and enhanced illness. Three different approaches were taken to dissect the region of G responsible for enhanced disease and protection against challenge. First, mutant viruses, containing frameshifts that altered the COOH terminus of the G protein, were used to challenge mice sensitized by scarification with recombinant vaccinia virus (rVV) expressing wild-type G. Second, cDNA expressing these mutated G proteins were expressed by rVV and used to vaccinate mice before challenge with wild-type respiratory syncytial virus (RSV). These studies identified residues 193–205 to be responsible for G-induced weight loss and lung eosinophilia and showed that this region was not was not necessary for induction of protective immunity. Third, mice were sensitized using an rVV that expressed only amino acids 124–203 of the G protein. Upon RSV challenge, mice sensitized with this rVV developed enhanced weight loss and eosinophilia. This is the first time that a region within RSV (amino acids 193–203) has been shown to be responsible for induction of lung eosinophilia and disease enhancement. Moreover, we now show that it is possible to induce protective immunity with an altered G protein without inducing a pathological response.
β cell replication is the primary mechanism for maintaining postnatal β cell mass
Authors: Senta Georgia, Anil Bhushan
Journal: Journal of Clinical Investigation (2004)

The endocrine pancreas undergoes major remodeling during neonatal development when replication of differentiated β cells is the major mechanism by which β cell mass is regulated. The molecular mechanisms that govern the replication of terminally differentiated β cells are unclear. We show that during neonatal development, cyclin D2 expression in the endocrine pancreas coincides with the replication of endocrine cells and a massive increase in islet mass. Using cyclin D2–/– mice, we demonstrate that cyclin D2 is required for the replication of endocrine cells but is expendable for exocrine and ductal cell replication. As a result, 14-day-old cyclin D2–/– mice display dramatically smaller islets and a 4-fold reduction in β cell mass in comparison to their WT littermates. Consistent with these morphological findings, the cyclin D2–/– mice are glucose intolerant. These results suggest that cyclin D2 plays a key role in regulating the transition of β cells from quiescence to replication and may provide a target for the development of therapeutic strategies to induce expansion and/or regeneration of β cells.
Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study
Authors: Grant A McArthur, Paul B Chapman, Caroline Robert, James Larkin, John B Haanen, Reinhard Dummer, Antoni Ribas, David Hogg, Omid Hamid, Paolo A Ascierto, Claus Garbe, Alessandro Testori, Michele Maio, Paul Lorigan, Celeste Lebbé, Thomas Jouary, Dirk Schadendorf, Stephen J O'Day, John M. Kirkwood, Alexander M Eggermont, Brigitte Dréno, Jeffrey A Sosman, Keith T Flaherty, Ming Yin, Ivor Caro, Suzanne Cheng, Kerstin Trunzer, Axel Hauschild
Journal: The Lancet Oncology (2014)
Principles of Drug Action: The Basis of Pharmacology.
Authors: Avram Goldstein, Lewis Aronow, Sumner M. Kalman
Journal: Annals of Internal Medicine (1975)

Molecular Basis of Pharmacologic Selectivity. Molecular Basis of Drug Action. The Entry, Distribution, And Elimination of Drugs. The Time Course of Drug Action. Pathways of Drug Metabolism. Molecular Aspects of Regulation and Structures of the Drug- Metabolizing Enzymes. Pharmacogenetics. Drug Allergy. Drug Resistance. Drug Tolerance and Physical Dependence. Chemical Mutagenesis. Chemical Carcinogenesis. Chemical Teratogenesis. Index
Effect of colchicine on intestinal function in the rat.
Authors: R J Levin
Journal: Gut (1966)

EDITORIAL SYNOPSIS Colchicine, being a powerful inhibitor of mitosis, might be expected to influence intestinal function in view of the rapid turnover of the cells of the mucosa.It has in fact been found to reduce absorption of certain sugars and also has an effect on motility and food intake in the rat.
Evaluation of a Self-Administered Sensory Testing Tool to Identify Patients at Risk of Diabetes-Related Foot Problems
Authors: James A Birke, Robert J Rolfsen
Journal: Diabetes Care (1998)

OBJECTIVE To study the use of a self-administered sensory testing tool designed to identify individuals at risk for diabetes-related foot problems and determine the inter-rater reliability between patient and provider sensory evaluations. RESEARCH DESIGN AND METHODS Nine centers in eight states with established foot prevention centers mailed 196 self-screening testing materials to randomly selected patients with diabetes scheduled for follow-up appointments. Patients were instructed to perform a sensory test using a 10-g nylon filament at specified sites on the foot and to complete a brief survey form before their appointment. During the follow-up appointment, providers retested patients using an identical sensory filament at the same sites and completed a provider survey. RESULTS Of the patients, 145 kept their appointments and completed the self-screening materials. There were 141 patient and 137 provider surveys that indicated the instructions were clear and easy to use. Sixty-eight percent of the patients reported self-testing without the assistance of another person. Patient and provider sensory test findings disagreed (P = 0.0014) in 18 of 145 cases and fair inter-rater reliability was found (κ = 0.73). Disagreement in sensory tests was related to patient age (P = 0.012). Sensory loss, previously undetected by providers, was found in 23 case subjects. CONCLUSIONS Self-administered sensory tests provide patients an opportunity to share in the responsibility for preventing diabetes-related foot problems but should not replace routine foot evaluation by a provider.
Reversibility of severe bleomycin-induced pneumonitis
Authors: W. G. Brown
Journal: JAMA (1978)

The use of bleomycin sulfate as an antineoplastic agent has been limited by its substantial pulmonary toxic effects. The exact incidence and prognosis of bleomycin-pneumonitis is unresolved. Although bleomycin pulmonary toxicity is thought to be dose-related, recent reports have emphasized severe reactions at low doses. Furthermore, severe pulmonary toxicity has been suggested to be progressive, irreversible, and ultimately, fatal. We report clinical, roentgenographic, and pathophysiologic recovery after severe, bleomycin-induced pneumonitis. (<i>JAMA</i>239:2012-2014, 1978)
Novel Genetic Mutations in a Sporadic Port-Wine Stain
Authors: Christine Guo Lian, Lynette M. Sholl, Labib R. Zakka, Teresa M. O, Cynthia Liu, Shuyun Xu, Ewelina Stanek, Elizabeth Garcia, Yonghui Jia, Laura E. MacConaill, George F. Murphy, Milton Waner, Martin C. Mihm
Journal: JAMA Dermatology (2014)

IMPORTANCE Port-wine stains (PWSs) are common congenital cutaneous capillary malformations. A somatic GNAQ mutation was recently identified in patients with sporadic PWSs and Sturge-Weber syndrome. However, subsequent studies to confirm or extend this observation are lacking.OBSERVATIONS We report a long-standing, unilateral facial PWS of a man in his early 70s confirmed by histopathological analysis. Staged surgical excision of the vascular malformation was performed, and genomic DNA was extracted from the vascular malformation specimen and normal skin. Targeted next-generation sequencing of the coding sequence of 275 known cancer genes including GNAQ was performed in both specimens. A single-nucleotide variant(c.548G>A, p.Arg183Gln) in GNAQ was identified in the PWS-affected tissue but not in the normal skin sample. In addition, this sequencing approach uncovered several additional novel somatic mutations in the genes SMARCA4, EPHA3, MYB, PDGFR-β, and PIK3CA.CONCLUSIONS AND RELEVANCE Our findings confirm the presence of somatic mutations inGNAQ in the affected skin of a patient with congenital PWS, as well as alterations in several other novel genes of possible importance in the pathogenesis of PWS that may also offer substantial therapeutic targets.
Celecoxib Inhibits Vascular Endothelial Growth Factor Expression in and Reduces Angiogenesis and Metastasis of Human Pancreatic Cancer via Suppression of Sp1 Transcription Factor Activity
Authors: Daoyan Wei, Liwei Wang, Yanjuan He, Henry Q. Xiong, James L. Abbruzzese, Keping Xie
Journal: Cancer Research (2004)

Abstract The aggressive biology of human pancreatic adenocarcinoma has been linked with overexpression of vascular endothelial growth factor (VEGF). Constitutive activation of the transcription factor Sp1 plays a critical role in VEGF overexpression. Recent studies indicated that celecoxib, a selective cyclooxygenase-2 inhibitor, exhibits potent antitumor activity. However, the underlying molecular mechanisms of this activity remain unclear. In the present study, we used a pancreatic cancer model to determine the role of Sp1 in the antitumor activity of celecoxib. Treatment of various pancreatic cancer cells with celecoxib suppressed VEGF expression at both the mRNA and protein level in a dose-dependent manner. VEGF promoter deletion and point mutation analyses indicated that a region between nucleotide −109 and −61 and its intact Sp1-binding sites were required for the inhibition of VEGF promoter activity by celecoxib. Also, celecoxib treatment reduced both Sp1 DNA binding activity and transactivating activity. This decreased activity correlated with reduced Sp1 protein and its phosphorylation as determined using Western blot analysis. Furthermore, in an orthotopic pancreatic cancer animal model, celecoxib treatment inhibited tumor growth and metastasis. The antitumor activity was consistent with inhibition of angiogenesis as determined by evaluating tumor microvessel formation, which correlated with decreased Sp1 activity and VEGF expression. Collectively, our data provide a novel molecular mechanism for the antitumor activity of celecoxib and may help further improve its effectiveness in controlling pancreatic cancer growth and metastasis.