tbuckley/cabot-search huggingface dataset:
Direct-to-Consumer Advertising in Oncology: A Content Analysis of Print Media
Authors: Gregory A. Abel, Stephanie J. Lee, Jane C. Weeks
Journal: Journal of Clinical Oncology (2007)

Content analysis of cancer-related direct-to-consumer advertising (DTCA), with a focus on how benefit and risk/adverse effect information is presented, is essential to understanding its potential impact on oncology outcomes.We reviewed all oncology DTCA appearing in three patient-focused cancer magazines and a sample of selected popular magazines from January 2003 to June 2006. We determined the Flesch reading ease score (FRES) for the text in each advertisement (a score > or = 65 is readable for the average person). We also assessed the proportion, type size, and placement of benefits and risks/adverse effects, as well as the nature and content of advertising appeals.Of 284 advertisements identified, 49 were unique. Oncology-related DTCA was rare in the popular magazines, and appeared mostly in those aimed at female readership. About equal amounts of text were devoted to benefits and risks/adverse effects, and all text was difficult to read. The mean FRES for benefit text was 39.71; for risk/adverse effect text, it was 38.22, a difference of 1.49 (95% CI, -4.02 to 7.00). The largest font size for benefits was 4.60 mm on average; for risks/adverse effects, it was 2.38 mm, a difference of 2.22 mm (95% CI, 1.35 to 3.09). Appeals to medication effectiveness were frequent (95%) and often made with clinical trial data (61%).Oncology print DTCA is prevalent in cancer-related, patient-directed magazines, and infrequent in the popular press. The information presented is considerably difficult to read, raising important questions about the appropriateness of direct-to-consumer marketing for oncologic medications.
Functional disorders of the biliary tract and pancreas
Authors: E Corazziari, E A Shaffer, W J Hogan, S Sherman, J Toouli
Journal: Gut (1999)

The term "dysfunction" defines the motor disorders of the gall bladder and the sphincter of Oddi (SO) without note of the potential etiologic factors for the difficulty to differentiate purely functional alterations from subtle structural changes. Dysfunction of the gall bladder and/or SO produces similar patterns of biliopancreatic pain and SO dysfunction may occur in the presence of the gall bladder. The symptom-based diagnostic criteria of gall bladder and SO dysfunction are episodes of severe steady pain located in the epigastrium and right upper abdominal quadrant which last at least 30 minutes. Gall bladder and SO dysfunctions can cause significant clinical symptoms but do not explain many instances of biliopancreatic type of pain. The syndrome of functional abdominal pain should be differentiated from gall bladder and SO dysfunction. In the diagnostic workup, invasive investigations should be performed only in the presence of compelling clinical evidence and after non-invasive testing has yielded negative findings. Gall bladder dysfunction is suspected when laboratory, ultrasonographic, and microscopic bile examination have excluded the presence of gallstones and other structural abnormalities. The finding of decreased gall bladder emptying at cholecystokinin-cholescintigraphy is the only objective characteristic of gall bladder dysfunction. Symptomatic manifestation of SO dysfunction may be accompanied by features of biliary obstruction (biliary-type SO dysfunction) or significant elevation of pancreatic enzymes and pancreatitis (pancreatic-type SO dysfunction). Biliary-type SO dysfunction occurs more frequently in postcholecystectomy patients who are categorized into three types. Types I and II, but not type III, have biochemical and cholangiographic features of biliary obstruction. Pancreatic-type SO dysfunction is less well classified into types. When non-invasive investigations and endoscopic retrograde cholangiopanreatography show no structural abnormality, manometry of both biliary and pancreatic sphincter may be considered.
Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase I NCI Organ Dysfunction Working Group Study NCI-6432
Authors: Patricia M. LoRusso, Karthik Venkatakrishnan, Ramesh K. Ramanathan, John Sarantopoulos, Daniel Mulkerin, Stephen I. Shibata, Anne Hamilton, Afshin Dowlati, Sridhar Mani, Michelle A. Rudek, Chris H. Takimoto, Rachel Neuwirth, Dixie-Lee Esseltine, Percy Ivy
Journal: Clinical Cancer Research (2012)

Abstract Purpose: The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Experimental Design: Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours postdose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results: Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions: Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. Clin Cancer Res; 18(10); 2954–63. ©2012 AACR.
Mechanical Regulation of Nuclear Structure and Function
Authors: Rui P. Martins, John D. Finan, Guilak Farshid, David A. Lee
Journal: Annual Review of Biomedical Engineering (2012)

Mechanical loading induces both nuclear distortion and alterations in gene expression in a variety of cell types. Mechanotransduction is the process by which extracellular mechanical forces can activate a number of well-studied cytoplasmic signaling cascades. Inevitably, such signals are transduced to the nucleus and induce transcription factor-mediated changes in gene expression. However, gene expression also can be regulated through alterations in nuclear architecture, providing direct control of genome function. One putative transduction mechanism for this phenomenon involves alterations in nuclear architecture that result from the mechanical perturbation of the cell. This perturbation is associated with direct mechanical strain or osmotic stress, which is transferred to the nucleus. This review describes the current state of knowledge relating the nuclear architecture and the transfer of mechanical forces to the nucleus mediated by the cytoskeleton, the nucleoskeleton, and the LINC (linker of the nucleoskeleton and cytoskeleton) complex. Moreover, remodeling of the nucleus induces alterations in nuclear stiffness, which may be associated with cell differentiation. These phenomena are discussed in relation to the potential influence of nuclear architecture-mediated mechanoregulation of transcription and cell fate.
Diabetes and serum ferritin concentration among U.S. adults.
Authors: E S Ford, M E Cogswell
Journal: Diabetes Care (1999)

OBJECTIVE: We examined the association between serum ferritin concentration and the risk of diabetes. RESEARCH DESIGN AND METHODS: We examined the cross-sectional associations among ferritin concentration, glucose tolerance status, and concentrations of insulin, glucose, and glycosylated hemoglobin in 9,486 U.S. adults aged &amp;gt; or = 20 years from the Third National Health and Nutrition Examination Survey (1988-1994). RESULTS: After adjusting for age, sex, ethnicity, education, BMI, alcohol consumption, alanine aminotransferase concentration, C-reactive protein concentration, and examination session attended, and after dichotomizing ferritin concentration into &amp;lt; 300 and &amp;gt; or = 300 micrograms/l for men and &amp;lt; 150 and &amp;gt; or = 150 micrograms/l for women, the odds ratios for newly diagnosed diabetes were 4.94 (95% CI 3.05-8.01) for men and 3.61 (2.01-6.48) for women. The increased risk of newly diagnosed diabetes was concentrated among participants with transferrin saturations &amp;lt; 45%. All multiple linear regression coefficients between ferritin concentration and concentrations of insulin, glucose, and glycosylated hemoglobin were positive and significant for both men and women. CONCLUSIONS: Elevated serum ferritin concentration was associated with an increased risk of diabetes. We were unable to eliminate conclusively the possibility that the observed association reflected inflammation rather than excess body iron stores.
Molecular Modeling and Functional Mapping of B7-H1 and B7-DC Uncouple Costimulatory Function from PD-1 Interaction
Authors: Shengdian Wang, Jürgen Bajorath, Dallas B. Flies, Haidong Dong, Tasuku Honjo, Lieping Chen
Journal: The Journal of Experimental Medicine (2003)

B7-H1 and B7-DC are ligands for PD-1, a receptor implicated in negative regulation of T and B cell functions. These ligands, however, also costimulate T cell responses. It remains elusive whether or not costimulation is mediated through PD-1. By comparative molecular modeling and site-directed mutagenesis, we found that nonconserved residues between these ligands on the A′GFCC′C′′ face mediate interaction with PD-1. This indicates significant structural heterogeneity of the interactions between PD-1 and its ligands. Importantly, ligand mutants with abolished PD-1 binding capacity could still costimulate proliferation and cytokine production of T cells from normal and PD-1–deficient mice. Our results reveal unique binding characteristics of B7-H1 and B7-DC and provide direct evidence for an independent costimulatory receptor other than PD-1.
A novel beta 4, alpha 6 integrin-associated epithelial cell antigen involved in natural killer cell and antigen-specific cytotoxic T lymphocyte cytotoxicity.
Authors: J H Phillips, L McKinney, M Azuma, H Spits, L L Lanier
Journal: The Journal of Experimental Medicine (1991)

Efficient immune responses require interactions between cell adhesion molecules on lymphocytes and counter-receptors on antigen presenting cells or target cells. While target-specific receptors or ligands have not been identified for natural killer (NK) cells, cell adhesion molecules have been implicated in the interaction between NK cell effectors and tumor cell targets. Herein, we describe monoclonal antibodies (mAbs) against a carcinoma cell line that efficiently block the cytolytic activity of interleukin 2-activated NK cell lines and clones. L280 mAb reacts with secretory epithelial cells in normal human tissues, but does not react with hematopoietic cells or other tissue types. Biochemical analysis revealed that L280 mAb immunoprecipitates the beta 4, alpha 6 integrin, as well as a novel 98-kD glycoprotein, and probably reacts with a carbohydrate epitope on these molecules. Involvement of the L280 antigen in cellular immunity is not restricted to NK cell-mediated cytotoxicity. L280 mAb also efficiently inhibits alloantigen-specific cytotoxicity against Colo-205 cells mediated by human histocompatibility leukocyte antigen (HLA)-A2 alloantigen specific alpha beta-TCR+ and gamma delta-TCR+ cytotoxic T lymphocyte (CTL) clones. Additionally, we demonstrate that L280 mAb blocks cytotoxicity mediated by influenza peptide-specific HLA-restricted CTL clones. These data indicate that the antigen recognized by L280 mAb is important in both NK and CTL function, and that an as yet unidentified receptor for this epithelial antigen is present on both NK and T lymphocytes. The restricted expression of L280 antigen indicates that this molecule may be important in immune reactions in epithelial tissues.
Structural and inflammatory sonographic findings in erosive and non-erosive osteoarthritis of the interphalangeal finger joints
Authors: Ruth Wittoek, Philippe Carron, Gust Verbruggen
Journal: Annals of the Rheumatic Diseases (2010)

Objective The objectives were: (1) to determine if ultrasound (US) can detect more erosions in erosive osteoarthritis (EOA) of the interphalangeal (IP) joints than conventional radiography (CR); and (2) to explore the frequency of structural and inflammatory findings in EOA and non-EOA. Methods Structural changes and the anatomical phase were scored on CR in IP joints of 31 patients with EOA and 7 patients with non-EOA. Structural and inflammatory changes were scored by US. The frequency of sonographic findings was compared between the anatomical phases and between EOA and non-EOA by generalised estimation equation (GEE) modelling. Results US detected 68 of 72 (94.4%) erosions seen on CR. US detected 45 additional erosive joints in EOA. The frequency of joint effusion and power Doppler signal was similar in EOA compared to non-EOA (p=0.91 and p=0.68, respectively). Statistically significantly more synovitis was present in full erosive phase compared to non-erosive phases in EOA (p=0.04). No differences in inflammatory findings were found between non-erosive phases in EOA and non-EOA. Conclusion US is capable of detecting erosions in radiographic non-erosive phases. The highest frequency of synovitis is present in erosive joints but inflammatory findings are common in all anatomical phases of EOA and non-EOA.
Optimum bile acid treatment for rapid gall stone dissolution.
Authors: R P Jazrawi, M G Pigozzi, G Galatola, A Lanzini, T C Northfield
Journal: Gut (1992)

To determine the optimum bile acid regimen for rapid gall stone dissolution, 48 gall stone patients were divided into four groups of 12 according to stone diameter and were randomly allocated to receive one of four treatment regimens: bedtime or mealtime chenodeoxycholic acid (CDCA, 12 mg/kg/day) and bedtime or mealtime ursodeoxycholic acid (UDCA, 12 mg/kg/day). An additional 10 patients treated with a combination of CDCA plus UDCA (each 6 mg/kg/day) at bedtime were matched with the 10 patients on bedtime CDCA and the 10 on bedtime UDCA. The gall stone dissolution rates at six and 12 months were determined by standardised oral cholecystography and expressed as the percentage reduction in the gall stone volume after treatment. The gall stone dissolution rate at six months was higher for UDCA than CDCA treatment (median 78% v 48%, p less than 0.01), and for bedtime than mealtime administration (69% v 39%, p less than 0.02). Both differences were greater for stones less than 8 mm diameter. The dissolution rate was faster for combination therapy than for CDCA alone at both six (82% v 36%, p less than 0.05) and 12 months (100% v 54%, p less than 0.05), but was not different from UDCA alone. We conclude that bile acid treatment should be confined to patients with small gall stones and that bedtime administration of combined UDCA and CDCA is likely to provide the most effective and safe combination.
Frontiers in Nephrology
Authors: Liisa K. Selin, Michael A. Brehm
Journal: Journal of the American Society of Nephrology (2007)

Established memory T cell responses to a previously encountered pathogen can have a major impact on the course and outcome of a subsequent infection with an unrelated pathogen. This phenomenon, known as heterologous immunity, is dependent on the sequence of infections and can be either beneficial or detrimental to the host. Examples of heterologous immunity between unrelated viruses and alloantigens are mounting, and the role of cross-reactive T cells both in the pathogenesis of infections and in transplant rejection is now being explored. Memory T cells seem to be part of a continually evolving interactive network in which with each new infection, an alteration in the frequencies, distributions, and activities of memory cells is generated in response to previous infections and alloantigens.
Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis.
Authors: M A Chapman, M F Grahn, M A Boyle, M Hutton, J Rogers, N S Williams
Journal: Gut (1994)

The short chain fatty acids, acetate, propionate, and butyrate are produced by colonic bacterial fermentation of non-starch polysaccharides. Butyrate is the major fuel source for the colonic epithelium and there is evidence to suggest that its oxidation is impaired in ulcerative colitis. Triplicate biopsy specimens were taken at colonoscopy from five regions of the large bowel in 15 sufferers of ulcerative colitis. These patients all had mild or quiescent colitis as assessed by clinical condition, mucosal endoscopic and histological appearance. The rate of oxidation of glucose, glutamine, and butyrate through to carbon dioxide was compared with that in biopsy specimens from 28 patients who had no mucosal abnormality. Butyrate (272 (199-368)) was the preferred fuel source for the colitic mucosa followed by glutamine (33 (24-62)) then glucose (7.2 (5.3-15)) pmol/micrograms/hour; medians and 95% confidence intervals, p &lt; 0.01. There was no regional difference in the rate of utilisation of these metabolites. In the group with colitis the rate of butyrate oxidation to carbon dioxide was significantly impaired compared with that in normal mucosa decreasing from 472 (351-637) pmol/micrograms/hour to 272 (199-368) pmol/micrograms/hour; median and 95% confidence intervals, p = 0.016. The rate of glucose and glutamine utilisation were not significantly different between normal and colitic mucosa. These data confirm that in quiescent ulcerative colitis there is an impairment of butyrate oxidation.
Re: Immediate Risk of Suicide and Cardiovascular Death After a Prostate Cancer Diagnosis: Cohort Study in the United States
Authors: P. Stattin, H. Garmo, G. Steineck, A. Bill-Axelson
Journal: JNCI Journal of the National Cancer Institute (2010)

Re: Immediate Risk of Suicide and Cardiovascular Death After a Prostate Cancer Diagnosis : Cohort Study in the United States
Microvascular correlates of blood pressure, plasma glucose, and insulin resistance in health
Authors: R Irving
Journal: Cardiovascular Research (2002)

Objectives: The associations between hypertension, insulin resistance and glucose intolerance are poorly understood. Altered microvascular structure and function could contribute by increasing peripheral vascular resistance and decreasing tissue delivery of glucose. We addressed this hypothesis in a sample of healthy men. Methods: We studied 105 healthy young men aged 23–33 years. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA). Video capillaroscopy was used on the dorsum of the finger to measure skin capillary density, and in nailfold capillaries to measure capillary blood velocity. Skin vasodilatation was measured with laser Doppler fluximetry on the forearm following heating and iontophoresis of acetylcholine. Results: Higher systolic blood pressure was associated with insulin resistance (r=0.31, P<0.005), lower dermal capillary density (r=−0.25, P<0.05), and impaired maximum dermal blood flow after heating (r=−0.26, P<0.01), but not with capillary blood velocity (r=0.07) or dilator responses to acetylcholine (r=0.09). Insulin resistance did not correlate with indices of microvascular structure or function (all r<±0.15). However, higher fasting plasma glucose was associated with lower capillary density (r=−0.27, P<0.01), and increased capillary blood velocity (r=0.30, P<0.05). Conclusions: The association between hypertension and insulin resistance is unlikely to be explained by altered microvascular structure and function. However, changes in the microvasculature are found in subjects with early and subtle elevations in blood pressure or fasting plasma glucose in advance of their crossing conventional thresholds for the diagnosis of hypertension or diabetes mellitus.
Elastic fibers and fibronectin expression in severe asthmatics
Authors: Diogenes Ferreira, Raquel Annoni, Regina Maria Carvalho-Pinto, Klaus Rabe, Alberto Cukier, Rafael Stelmach, Marisa Dolhnikoff, Thais Mauad
Journal: European Respiratory Journal (2013)

Introduction: Deposition of extracellular matrix occurs in the airways of severe asthmatics but how this impacts on airway function is unclear. We aimed to investigate elastic fibers and fibronectin content in the airways of severe asthmatics and their association with airway function.

Methods: Sixty-two severe asthmatics received a 2-week oral corticosteroid (OC) trial (40 mg/day prednisone) plus 800 µg budesonide + 24 µg formoterol as daily maintenance therapy and 200 µg budesonide + 6 µg formoterol as rescue medication for 12 weeks. All patients were non- or ex-smokers ≤ 10 pack-years. Patients were classified based on post-bronchodilator (BD) lung function after the 2-week OC trial into 3 groups: non-persistent obstruction (NPO: FEV1 ≥ 80%pred + FEV1/FVC > 0.70), persistent obstruction (PO: FEV1 > 50% and < 80%pred + FEV1/FVC ≤ 0.70) or fixed obstruction (FO: FEV1 ≤ 50%pred + FEV1/FVC ≤ 0.70). Endobronchial biopsies were performed at the end of 12 weeks. Elastic fibers and fibronectin were quantified by histochemistry and immunohistochemistry, respectively, and by digital image analysis in the bronchi inner layer (IL) and within the airway smooth muscle bundles (ASM). This study was approved by the University of Sao Paulo Clinics Hospital Ethics Committee.

Results: Fourteen patients were classified as NPO, 36 as PO and 12 as FO. Elastic fibers and fibronectin airway content were not different among the groups. Elastic fibers in the ASM correlated with post-BD FEV1 %change in the NPO group (r = - 0.764, p = 0.006) and PO group (r = - 0.382, p = 0.049) but not in asthmatics with FO.

Conclusion: Elastic fibers content within the ASM may impact on airway function of severe asthmatics without fixed airway obstruction.
Ménétrier’s Disease Therapy: Rebooting Mucosal Signaling
Authors: Sam C. Nalle, Jerrold R. Turner
Journal: Science Translational Medicine (2009)

Ménétrier's disease, a rare hyperproliferative disorder of the stomach, is associated with chronic abdominal pain, vomiting, weight loss, and edema, as well as an increased risk of gastric cancer. Therapy, other than surgical resection of the stomach, is limited to supportive measures and reflects the limited understanding of Ménétrier's disease pathogenesis. Data reported in this issue describe a promising targeted therapeutic approach and provide new insight into the causes of Ménétrier's disease.