tbuckley/cabot-search huggingface dataset:
Please, Let My Doctor Be Obese
Authors: Lielith J. Ubink-Veltmaat, Roger A.J.M. Damoiseaux, Roel O. Rischen, Klaas H. Groenier
Journal: Diabetes Care (2004)

Obesity is an important cardiovascular risk factor in type 2 diabetes (1). Physician characteristics such as age and sex are related to counseling for overweight (2). Other physician characteristics may also be related. Patients indicated greater confidence in nonobese versus obese physicians. Whether this translates into increased success in obesity management is unknown (3). We aimed to study associations between the weight of general practitioners and their type 2 diabetic patients.

A postal survey was performed among 36 general practitioners participating in a shared-care diabetes project in 2000. It …
Anterior Gradient 2 Is Expressed and Secreted during the Development of Pancreatic Cancer and Promotes Cancer Cell Survival
Authors: Vijaya Ramachandran, Thiruvengadam Arumugam, Huamin Wang, Craig D. Logsdon
Journal: Cancer Research (2008)

Abstract Pancreatic cancer is a major oncological challenge due to its aggressive growth and metastasis. In the current study, we investigated the role of anterior gradient 2 (AGR2) in these processes. AGR2 mRNA, as assessed by quantitative real-time reverse transcription–PCR (Q-RT-PCR), was 14-fold higher in pancreatic cancer compared with normal and pancreatitis tissues. Immunohistochemistry revealed high expression of AGR2 in neoplastic cells with 98% (56 of 57) positivity on pancreatic cancer and minimal staining in normal and pancreatitis tissues. AGR2 was also expressed in early pancreatic intraepithelial neoplastic lesions. RT-PCR and Western blotting showed elevated AGR2 expression in seven of nine pancreatic cancer cell lines. AGR2, as detected in conditioned media from cancer cells, indicated that it was secreted. The influence of AGR2 on pancreatic cancer cells was evaluated by silencing with small interfering RNA and short hairpin RNA. Silencing of AGR2 significantly reduced cell proliferation (MTS assay) and invasion (Boyden chamber assay) and improved gemcitabine sensitivity (fluorescence-activated cell sorting analysis). Conditioned media from cells in which AGR2 was silenced had a reduced ability to stimulate proliferation of pancreatic cancer cells, suggesting that secreted AGR2 was active. In vivo, silencing of AGR2 in MPanc-96 cells led to a significant reduction of tumor growth and increased the effectiveness of gemcitabine treatments in orthotopic tumor models evaluated by noninvasive bioluminescence imaging. In summary, AGR2 is expressed and secreted during pancreatic cancer development and plays an important role in cancer cell growth and survival. These observations suggest that AGR2 may be a useful molecular target in pancreatic cancer. [Cancer Res 2008;68(19):7811–8]
Docetaxel: an Active New Drug for Treatment of Advanced Epithelial Ovarian Cancer
Authors: M. J. Piccart, M. Gore, W. T. B. Huinink, A. Van Oosterom, J. Verweij, J. Wanders, H. Frankli, M. Bayssas, S. Kaye
Journal: JNCI Journal of the National Cancer Institute (1995)

Because of the relative scarcity of natural paclitaxel (Taxol), which has been recently recognized as a highly cytotoxic agent for use in platinum-refractory ovarian cancer, synthetic and semisynthetic substitutes have been actively pursued. Docetaxel (Taxotere), a new semisynthetic taxoid, has been selected for clinical development because it is twice as potent as paclitaxel in promoting assembly of tubulin and in inhibiting microtubule depolymerization. Docetaxel also shows equal or greater cytotoxicity in relevant preclinical models. Purpose: Because docetaxel has produced consistent antitumor responses in ovarian cancer patients in phase I trials, we planned and conducted a phase II clinical trial to evaluate the drug's effectiveness and its toxic effects. Methods: The present trial, which started in May 1992 and ended in December 1992, involved 97 patients with advanced epithelial ovarian cancer. The target study population had disease relapse or disease progression within 12 months of the last administration of a first-line or second-line platinum-based regimen with at least one bidimensionally measurable target lesion. The patients received docetaxel at a dose of 100 mg/m2 given as a 1-hour infusion every 3 weeks without premedication for minimizing potential hypersensitivity. Docetaxel-induced side effects were graded according to the National Cancer Institute's Common Toxicity Criteria. Results: The overall response rate was 23.6% in 76 assessable patients versus 20% if all 90 eligible patients were included in the comparison (95% confidence interval [CI] = ll%–29%). Among 34 eligible patients whose tumor progressed on the most recent platinum treatment, the response rate was 23.5% (95% CI = 8%–39%). The median progression-free survival for all eligible patients was 3.9 months, and the median overall survival was 8.4 months. Docetaxel-as-sociated toxicity in 90 assessable patients consisted of short-lived neutropenia in 81 (90%) patients, which was complicated by fever and hospitalization in seven (8%); hypersensitivity reactions were seen in 29 (31%) patients, with significant reactions seen in seven (8%); and neurotoxicity in 43 (48%) patients, with grade 3 or above toxicity seen in only three (3%). The treatment also produced skin reactions in 58 (64%) patients, of whom only four (4%) showed the intensity of grade 3. Eleven (12%) patients experienced pleural effusions, which were the effects of the drug considered to be of greatest concern. Peripheral edema and weight gain due to fluid retention were reported in 40 (44%) and 17 (19%) patients, respectively. Conclusion: Docetaxel appears to be effective in the treatment of platinum-refractory ovarian cancer patients. [J Natl Cancer Inst 87: 676–681, 1995]
IN VITRO TRANSFORMATION OF PNEUMOCOCCAL TYPES
Authors: Martin H. Dawson, Richard H. P. Sia
Journal: The Journal of Experimental Medicine (1931)

1. Type-specific S pneumococci may be transformed from one specific S type into other specific S types entirely by in vitro methods. 2. R forms of pneumococci, derived from S forms of one specific type, may be transformed into S forms of other specific types by the following in vitro procedure:-the growth of small inocula of R forms in media containing vaccines prepared from heterologous S cultures. 3. Transformation of type may be effected in this procedure by the use of small quantities of S vaccine,-quantities representing the bacteria from as little as 0.1 cc. of the original culture. 4. Transformation of type, as induced by this procedure, is most readily effected by employing anti-R serum in the culture medium. Transformation of type may be effected, however, in media which do not contain anti-R antibodies. 5. Previous findings on the thermal characteristics of the property of S vaccines responsible for transformation of type have been confirmed and extended.
Heart rate in relation to insulin sensitivity and insulin secretion in nondiabetic subjects.
Authors: A Festa, R D'Agostino, C N Hales, L Mykkänen, S M Haffner
Journal: Diabetes Care (2000)

OBJECTIVE: Elevated heart rate has been predictive of cardiovascular disease and has been proposed as a global index of the autonomic nervous system influence on the heart. Hyperinsulinism has been shown to trigger sympathetic activity experimentally; however, the clinical and epidemiological data on the association of heart rate with hyperinsulinism and insulin resistance are conflicting. RESEARCH DESIGN AND METHODS: Insulin sensitivity (S(I)) and the acute insulin response (AIR) to glucose were assessed by a frequently sampled intravenous glucose tolerance test and related to resting heart rate in the tri-ethnic nondiabetic population (n = 1,000) of the Insulin Resistance Atherosclerosis Study. RESULTS: Heart rate was related to fasting insulin (r = 0.20), intact proinsulin (r = 0.15), split proinsulin (r = 0.17), and AIR (r = 0.18), and an inverse relation was found between heart rate and S(I) (r = -0.19) (all P values &amp;lt;0.0001, adjusted for age, sex, ethnicity, glucose tolerance status, and smoking). In a multiple linear regression analysis (adjusting for age, sex, ethnicity, clinical center, glucose tolerance status, and smoking), heart rate was significantly and independently associated with AIR, proinsulin, and S(I). CONCLUSIONS: Proinsulin, acute insulin secretion, and S(I) are associated with heart rate in nondiabetic subjects.
Longitudinal Change in CSF Biomarkers in Autosomal-Dominant Alzheimer’s Disease
Authors: Anne M. Fagan, Chengjie Xiong, Mateusz S. Jasielec, Randall J. Bateman, Alison M. Goate, Tammie L. S. Benzinger, Bernardino Ghetti, Ralph N. Martins, Colin L. Masters, Richard Mayeux, John M. Ringman, Martin N. Rossor, Stephen Salloway, Peter R. Schofield, Reisa A. Sperling, Daniel Marcus, Nigel J. Cairns, Virginia D. Buckles, Jack H. Ladenson, John C. Morris, David M. Holtzman
Journal: Science Translational Medicine (2014)

Longitudinal cerebrospinal fluid biomarker analyses reveal decreases in neuronal injury markers in later stages of autosomal-dominant Alzheimer’s disease.
Lymphatic and blood microvasculature organisation in pulmonary sarcoid granulomas
Authors: M. Kambouchner, D. Pirici, J-F. Uhl, L. Mogoanta, D. Valeyre, J-F. Bernaudin
Journal: European Respiratory Journal (2010)

Pulmonary sarcoid granulomas are characterised by their elective distribution along collecting lymphatics. However, relationships between granulomas and intralobular lymphatics or blood microvascularisation have not been investigated. Therefore, we undertook a specific analysis of blood capillaries and lymphatics supplying sarcoid granulomas to identify additional clues to understanding the pathophysiogenesis of these lesions. Six pulmonary samples were immunolabelled with D2-40, anti-CD34 and anti-CD31 antibodies, paying particular attention to the relationships between lymphatics and granulomas, and the pattern of blood microvessels supplying sarcoid lesions. A morphometric study of granulomas included their distance to lymphatics and a three-dimensional reconstruction of a granuloma in its lymphatic context. Intralobular granulomas were closely associated with lymphatics; apart from a few granulomas, blood capillaries stopped at the outer border of the fibrous ring surrounding granulomas, and perigranuloma capillaries were particularly scarce. Our observations of the lymphatic and blood microvascular environment of intralobular pulmonary sarcoid granulomas provide evidence for the critical role of lymphatics in the emergence of these lesions. Moreover, pulmonary sarcoid lesions could be considered avascular structures, thereby providing new insights into the understanding of the granuloma physiology and the distribution of blood-borne therapeutic agents.
Treatment of Hyperlipidemia
Authors: John P. Kane, Mary J. Malloy
Journal: Annual Review of Medicine (1990)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
FGF-1–Induced Platelet-Derived Growth Factor-A Chain Gene Expression in Endothelial Cells Involves Transcriptional Activation by Early Growth Response Factor-1
Authors: Gabrielle J. Delbridge, Levon M. Khachigian
Journal: Circulation Research (1997)

Abstract Fibroblast growth factor-1 (FGF-1), a prototype member of the heparin-binding growth factor family, is a potent mitogen for vascular endothelial cells and a variety of other cell types. FGF-1 can induce the expression of the platelet-derived growth factor-A chain (PDGF-A) gene in endothelial cells; however, the underlying transcriptional mechanisms are not known. We used serial 5′ deletion and transient transfection analysis of the human PDGF-A promoter to demonstrate that a 16-bp element, located 55 to 71 bp upstream of the transcriptional start site, is required for FGF-1–inducible promoter–dependent expression. This region contains nucleotide recognition elements for the early growth response gene product, early growth response factor-1 (Egr-1), and the related zinc-finger transcription factor, Sp1. Reverse-transcription polymerase chain reaction revealed that FGF-1 induced Egr-1 mRNA expression within 30 minutes. Electrophoretic mobility shift, supershift, and Western blot analysis demonstrated that Egr-1 protein accumulated in the nuclei of endothelial cells exposed to the growth factor, whereas levels of Sp1 did not change. Egr-1 bound to the FGF-1 response element in the proximal PDGF-A promoter in a specific and time-dependent manner. These findings indicate that Egr-1 plays a key regulatory role in FGF-1–inducible endothelial PDGF-A expression and implicate this transcription factor in pathological settings in which these mitogens are both expressed.
Regulatory T Cells in the Control of Autoimmunity: the Essential Role of Transforming Growth Factor β and Interleukin 4 in the Prevention of Autoimmune Thyroiditis in Rats by Peripheral CD4+CD45RC− Cells and CD4+CD8− Thymocytes
Authors: Benedict Seddon, Don Mason
Journal: The Journal of Experimental Medicine (1999)

Previous studies have shown that induction of autoimmune diabetes by adult thymectomy and split dose irradiation of PVG.RT1u rats can be prevented by their reconstitution with peripheral CD4+CD45RC−TCR-α/β+RT6+ cells and CD4+CD8− thymocytes from normal syngeneic donors. These data provide evidence for the role of regulatory T cells in the prevention of a tissue-specific autoimmune disease but the mode of action of these cells has not been reported previously. In this study, autoimmune thyroiditis was induced in PVG.RT1c rats using a similar protocol of thymectomy and irradiation. Although a cell-mediated mechanism has been implicated in the pathogenesis of diabetes in PVG.RT1u rats, development of thyroiditis is independent of CD8+ T cells and is characterized by high titers of immunoglobulin (Ig)G1 antithyroglobulin antibodies, indicating a major humoral component in the pathogenesis of disease. As with autoimmune diabetes in PVG.RT1u rats, development of thyroiditis was prevented by the transfer of CD4+CD45RC− and CD4+CD8− thymocytes from normal donors but not by CD4+CD45RC+ peripheral T cells. We now show that transforming growth factor (TGF)-β and interleukin (IL)-4 both play essential roles in the mechanism of this protection since administration of monoclonal antibodies that block the biological activity of either of these cytokines abrogates the protective effect of the donor cells in the recipient rats. The prevention of both diabetes and thyroiditis by CD4+CD45RC− peripheral cells and CD4+CD8− thymocytes therefore does not support the view that the mechanism of regulation involves a switch from a T helper cell type 1 (Th1) to a Th2-like response, but rather relies upon a specific suppression of the autoimmune responses involving TGF-β and IL-4. The observation that the same two cytokines were implicated in the protective mechanism, whether thymocytes or peripheral cells were used to prevent autoimmunity, strongly suggests that the regulatory cells from both sources act in the same way and that the thymocytes are programmed in the periphery for their protective role. The implications of this result with respect to immunological homeostasis are discussed.
Xenografted Adult Human Mesenchymal Stem Cells Provide a Platform for Sustained Biological Pacemaker Function in Canine Heart
Authors: Alexei N. Plotnikov, Iryna Shlapakova, Matthias J. Szabolcs, Peter Danilo, Beverly H. Lorell, Irina A. Potapova, Zhongju Lu, Amy B. Rosen, Richard T. Mathias, Peter R. Brink, Richard B. Robinson, Ira S. Cohen, Michael R. Rosen
Journal: Circulation (2007)

Biological pacemaking has been performed with viral vectors, human embryonic stem cells, and adult human mesenchymal stem cells (hMSCs) as delivery systems. Only with human embryonic stem cells are data available regarding stability for >2 to 3 weeks, and here, immunosuppression has been used to facilitate survival of xenografts. The purpose of the present study was to determine whether hMSCs provide stable impulse initiation over 6 weeks without the use of immunosuppression, the "dose" of hMSCs that ensures function over this period, and the catecholamine responsiveness of hMSC-packaged pacemakers.A full-length mHCN2 cDNA subcloned in a pIRES2-EGFP vector was electroporated into hMSCs. Transfection efficiency was estimated by GFP expression. I(HCN2) was measured with patch clamp, and cells were administered into the left ventricular anterior wall of adult dogs in complete heart block and with backup electronic pacemakers. Studies encompassed 6 weeks. I(HCN2) for all cells was 32.1+/-1.3 pA/pF (mean+/-SE) at -150 mV. Pacemaker function in intact dogs required 10 to 12 days to fully stabilize and persisted consistently through day 42 in dogs receiving > or =700,000 hMSCs (approximately 40% of which carried current). Rhythms were catecholamine responsive. Tissues from animals killed at 42 days manifested neither apoptosis nor humoral or cellular rejection.hMSCs provide a means for administering catecholamine-responsive biological pacemakers that function stably for 6 weeks and manifest no cellular or humoral rejection at that time. Cell doses >700,000 are sufficient for pacemaking when administered to left ventricular myocardium.
Prostaglandin E2 suppresses staphylococcal enterotoxin–induced eosinophilia-associated cellular responses dominantly through an E-prostanoid 2–mediated pathway in nasal polyps
Authors: Mitsuhiro Okano, Tazuko Fujiwara, Takenori Haruna, Shin Kariya, Seiichiro Makihara, Takaya Higaki, Kazunori Nishizaki
Journal: Journal of Allergy and Clinical Immunology (2009)
Pulmonary Vasomotor Responses to Epinephrine and Norepinephrine in the Cat
Authors: HELEN N. DUKE, R. D. STEDEFORD
Journal: Circulation Research (1960)

Constant intravenous infusion of epinephrine has no effect on the pulmonary vascular resistance (P.V.R.) of the cat under chloralose anesthesia, either when the chest is opened and artificial ventilation is used, or when the animal is respiring naturally. The same dose of epinephrine given after removal of the stellate ganglia and upper 4 to 5 thoracic sympathetic ganglia, can cause an increase of P.V.R. Removal of such ganglia causes a decrease of P.V.R. Electrical stimulation of the cardiac branches from both stellate ganglia causes either an increase or a decrease of P.V.R. Increases of P.V.R. have been produced by intravenous infusion of norepinephrine.
Exonic expression profiling of breast cancer and benign lesions: a retrospective analysis
Authors: Fabrice André, Stefan Michiels, Philippe Dessen, Veronique Scott, Voichita Suciu, Catherine Uzan, Vladimir Lazar, Ludovic Lacroix, Gilles Vassal, Marc Spielmann, Philippe Vielh, Suzette Delaloge
Journal: The Lancet Oncology (2009)
IMMUNOREACTIONS INVOLVING PLATELETS
Authors: N. Raphael Shulman
Journal: The Journal of Experimental Medicine (1958)

A steric and kinetic model for the sequence and mechanism of reactions leading to formation of a complex from an antibody, a haptene (quinidine), and a cell membrane (platelets), and to fixation of complement by the complex was deduced from the effects of varying the initial concentration of each component of the complex on the amount of complement fixed, from kinetic aspects of the sequential reactions, and from other chemical and physical properties of the various components involved. Theoretical results calculated using equations based on the model, which were derived by Dr. Terrell L. Hill, were similar in all respects to experimental results. Results of this study were consistent with the possibilities that the protein moiety of a haptenic antigen involved in development of an antibody which attaches to a cell is not necessarily a component of the cell, and that the cell reacts with the antibody by virtue of having a surface favorable for non-specific adsorption of certain haptene-antibody complexes.
Migrant tuberculosis screening in the EU/EEA: yield, coverage and limitations
Authors: E. Klinkenberg, D. Manissero, J. C. Semenza, S. Verver
Journal: European Respiratory Journal (2009)

A systematic literature review was performed with the objective of assessing the effectiveness of tuberculosis (TB) screening methods and strategies in migrants in European Union/European Economic Area (including Switzerland) countries. Extracted data on yield and coverage were used as indicators of effectiveness. Reported yields varied considerably between studies and countries. Considering only the 14 studies representative of national screening programmes, a median yield of TB disease of 0.18% (interquartile range 0.10–0.35%) was reported. The data did not indicate differences in effectiveness between the three main strategies: 1) screening at port of entry; 2) screening just after arrival in reception/holding centres; and 3) screening in the community following arrival in European Union countries. The variation seen probably reflects variation in risk factors for TB, in particular the composition of the migrants entering the country. Recommendations include the need for improved data for guiding the optimal frequency and duration of screening; assessment and improvement of cost-effectiveness; access to healthcare for migrants, including illegal migrants; ensuring a continuum of care for those screened; and consideration of screening for latent TB infection with caution. Finally, screening should be a component of a wider approach, rather than a stand-alone intervention.
ELAC2/HPC2 Polymorphisms, Prostate-Specific Antigen Levels, and Prostate Cancer
Authors: G. Severi, G. G. Giles, M. C. Southey, A. Tesoriero, W. Tilley, P. Neufing, H. Morris, D. R. English, M. R. E. McCredie, P. Boyle, J. L. Hopper
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: The ELAC2 gene has been proposed to be a prostate cancer susceptibility gene and is being referred to as HPC2, in part because three case–control studies suggested that two common polymorphisms (Ser217Leu and Ala541Thr) are associated with risk. However, four subsequent larger studies have not confirmed this association. In five of the seven total studies, subject selection was influenced by prostate-specific antigen (PSA) levels. We examined the association and possible effect of subject selection in a larger study and a meta-analysis. Methods: In a population-based study in Australia, 825 case patients and 732 control subjects were genotyped for the Ser217Leu and Ala541Thr polymorphisms of ELAC2. Odds ratios (ORs) for prostate cancer were estimated by unconditional logistic and polytomous regression. A meta-analysis was conducted combining our data with those from seven published studies. The association of genotype with the logarithm of plasma PSA levels in control subjects was analyzed by linear regression. Results: The ORs for prostate cancer were 0.74 (95% confidence interval [CI] = 0.50 to 1.09) for Leu217 homozygotes and 1.01 (95% CI = 0.68 to 1.50) for Thr541 heterozygotes and homozygotes compared with Ser217 and Ala541 homozygotes, respectively. ORs were not changed by excluding control subjects with elevated PSA levels. Among control subjects, there were no statistically significant associations between genotype frequencies and PSA level for either polymorphism (both P>.4). The meta-analysis gave pooled OR estimates of 1.04 (95% CI = 0.85 to 1.26) for Leu217 homozygotes and 1.18 (OR = 0.98 to 1.42) for Thr541 homozygotes and heterozygotes. Conclusion: There is no evidence that either ELAC2 polymorphism is associated with prostate cancer or PSA level.