tbuckley/cabot-search huggingface dataset:
Descriptive and Prognostic Value of Patient-Reported Outcomes: The Bortezomib Experience in Relapsed and Refractory Multiple Myeloma
Authors: Dominique Dubois, Ravinder Dhawan, Helgi van de Velde, Dixie Esseltine, Sanjay Gupta, Muriel Viala, Christine de la Loge
Journal: Journal of Clinical Oncology (2006)

Purpose Bortezomib, a boronic acid dipeptide, has been recently introduced as a new approach to treating multiple myeloma (MM). The goal of this work was to evaluate the added value of patient-reported outcomes (PRO) in the interpretation of bortezomib clinical trial outcomes. Patients and Methods Two hundred two patients with relapsed, refractory MM were treated with bortezomib as part of the SUMMIT (Study of Uncontrolled Multiple Myeloma Managed with Proteasome Inhibition Therapy) study. Patients were administered the following four PRO measures at several time points: the European Organisation for Research and Treatment of Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) and the myeloma-specific module (QLQ-MY24), the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale, and the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG) Neurotoxicity (Ntx) scale. Minimal important difference (MID) thresholds were used to define patients as improved, stable, or worsened. A survival analysis was conducted to assess the predictive power of PRO data. Results For the total population, there was a positive change between baseline and best end point. Consistent with the clinical responses, change in PRO scores showed statistically significant differences between response groups with PRO improvement in patients with complete response (CR) or partial response (PR), mostly stable scores in patients with minor response or no change, and deterioration in most scores for patients with progressive disease. Change in scores for neuropathy-related symptoms was reasonably stable. In contrast, fatigue scores significantly improved for patients with CR or PR. When various MID thresholds were applied, the proportion of improved patients exceeded 35% for several domains within all change group definitions. Moreover, survival analysis results demonstrated the additional prognostic information PRO data can provide to supplement clinical data. Conclusion This study demonstrated the complementary value for PRO assessments in further interpreting clinical response, the impact of adverse effects, and patient prognosis in clinical trials.
Changes in lipid profile during infliximab and corticosteroid treatment in rheumatoid arthritis
Authors: M J L Peters, M Vis, V P van Halm, G J Wolbink, A E Voskuyl, W F Lems, B A C Dijkmans, J W R Twisk, M H M T de Koning, R J van de Stadt, M T Nurmohamed
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objective:</b> To evaluate the effects of infliximab and corticosteroid treatment on the lipid profile in patients with active rheumatoid arthritis (RA). <b>Methods:</b> Infliximab infusions were given at weeks 0, 2, 6 and then every 8 weeks. Before each infusion, disease activity parameters (Disease Activity Index 28-Joint Score (DAS28)) C reactive protein (CRP) and lipid levels (total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein A1 (apo A1) and apolipoprotein B) were measured in 80 consecutive patients with RA, who completed the study period of 48 weeks. Longitudinal analyses were used to investigate (1) the course of lipid levels over a period of time and (2) the relationship between lipids, prednisone dose and disease activity. <b>Results:</b> Infliximab treatment causes a significant reduction in disease activity and a concomitant decrease in prednisone dose. Although they initially improved significantly, all lipid levels had returned to baseline levels after 48 weeks, except for apo A1. Longitudinal analyses revealed significant yet opposite associations between lipid levels and disease activity and between lipid levels and prednisone dose. DAS28 improvement by 1 point was associated with an increase of 0.016 mmol/l (0.618 mg/dl) total cholesterol and 0.045 mmol/l (1.737 mg/dl) HDL-cholesterol. Reduction of 10 mg prednisone was associated with a decrease of 0.04 mmol/l (1.544 mg/dl) total cholesterol and 0.16 mmol/l (6.177 mg/dl) HDL-cholesterol. <b>Conclusion:</b> Overall, no changes in serum lipid levels were observed after 48 weeks of infliximab treatment. The initial beneficial effects of infliximab on the lipid profile, by means of a reduction of disease activity, are attenuated by a concomitant decrease in prednisone dose.
Corrigendum to “Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype” [J Hepatol 2013; 59:957–963]
Authors: Hwalih Han, Mazen Noureddin, Michael Witthaus, Yoon J. Park, Jay H. Hoofnagle, T. Jake Liang, Yaron Rotman
Journal: Journal of Hepatology (2014)
Emotional activation of limbic circuitry in elderly normal subjects in a PET study
Authors: S Paradiso, R G Robinson, N C Andreasen, J E Downhill, R J Davidson, P T Kirchner, G L Watkins, L L Ponto, R D Hichwa
Journal: American Journal of Psychiatry (1997)

This study was undertaken to identify brain structures associated with emotion in normal elderly subjects.Eight normal subjects aged 55-78 years were shown film clips intended to provoke the emotions of happiness, fear, or disgust as well as a neutral state. During emotional activation, regional cerebral blood flow was measured with the use of [15O]H2O positron emission tomography imaging, and subjective emotional responses were recorded. Data were analyzed by subtracting the values during the neutral condition from the values in the various emotional activations.The stimuli produced a general activation in visual pathways that included the primary and secondary visual cortex, involving regions associated with object and spatial recognition. In addition, the specific emotions produced different regional limbic activations, which suggests that different pathways may be used for different types of emotional stimuli.Emotional activation in normal elderly subjects was associated with increases in blood flow in limbic and paralimbic brain structures. Brain activation may be specific to the emotion being elicited but probably involves complex sensory, association, and memory circuitry. Further studies are needed to identify activations that are specific for emotion.
A Behavior Rating Scale for Assessing Improvement in Behaviorally Deviant Children: A Preliminary Investigation
Authors: SAMUEL KUPIETZ, IRV BIALER, BERTRAND G. WINSBERG
Journal: American Journal of Psychiatry (1972)

Employing a recently developed behavior rating scale (BRS), it was found that the factors for aggressivity and for hyperactivity clearly differentiated among children in an outpatient psychiatric clinic, in a special school, and in public schools. In addition, significant improvement was shown on both factors after drug treatment of the psychiatric group. The authors concluded that the BRS is useful as a measure of deviant behavior as well as for assessing improvement following drug therapy.
Conditional Survival and the Choice of Conditioning Set for Patients With Colon Cancer: An Analysis of NSABP Trials C-03 Through C-07
Authors: Beth A. Zamboni, Greg Yothers, Mehee Choi, Clifton D. Fuller, James J. Dignam, Peter C. Raich, Charles R. Thomas, Michael J. O'Connell, Norman Wolmark, Samuel J. Wang
Journal: Journal of Clinical Oncology (2010)

Purpose Colon cancer overall survival (OS) is usually computed from the time of diagnosis. Survival gives the initial prognosis but does not reflect how prognosis changes with changing hazard rates over time. Conditional survival (probability of surviving y additional years given they have survived x years [CS or OS|OS]) is an alternative measure that accounts for elapsed time since diagnosis, providing more relevant prognostic information. We extend the concept of CS to condition on the set of patients alive, recurrence-free, and second primary cancer-free (disease-free survival [OS|DFS]). Patients and Methods Using data from National Surgical Adjuvant Breast and Bowel Project trials C-03 through C-07, 5-year OS|DFS was calculated on patients who were disease free up to 5 years after diagnosis, stratified by age, stage, nodal status, and performance status (PS). Results For stage II, OS|DFS improved from 87% to 92% at 5 years. For stage III, OS|DFS improved from 69% to 88%. Patients younger than 50 years showed OS|DFS improvement from 79% to 95%; those older than 70 years showed no sustained increase in OS|DFS. Node-negative patients with ≥ 12 nodes resected showed little change (89% to 94%); those with more than four positive nodes showed an improvement (57% to 86%). Patients with a PS of 0 or 1 demonstrated a small improvement; those with a PS of 2 did not (64% to 58%). Conclusion Prognosis improves over time for almost all groups of patients with colon cancer, especially those with positive nodes. OS|DFS is a more relevant measure of prognosis for those who have already survived disease free a period of time after diagnosis.
Deficient control of in vitro Epstein-Barr virus infection in patients with ankylosing spondylitis.
Authors: S Robinson, G S Panayi
Journal: Annals of the Rheumatic Diseases (1986)

Infectious Epstein-Barr (EB) virus obtained from the B95-8 marmoset cell line was used to infect mononuclear cells from healthy controls and patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and outgrowth of B cells into lymphoblastoid cell lines was assessed by visual microscopy and uptake of tritiated thymidine over a 28 day period. When undiluted virus was used lymphocytes from both patients with AS and RA and from normal controls outgrew into lymphoblastoid cell lines (LCLs) by day 28 of culture. At dilutions of 1/10, 1/20, and 1/40, however, the control cells showed regression of proliferation at approximately day 14 of culture, whereas the cells from patients with AS and RA continued to proliferate and outgrew into LCLs (transformation scores of cells from patients with AS compared with controls at day 28 p less than 0.05 in all cases; thymidine uptake at a 1/40 dilution at day 28, patients with AS compared with controls p less than 0.01). Hence these results suggest that there is a defect in the cellular response to EB virus induced B cell proliferation in patients with AS similar to that seen with cells from RA donors.
A gp91phox Containing NADPH Oxidase Selectively Expressed in Endothelial Cells Is a Major Source of Oxygen Radical Generation in the Arterial Wall
Authors: A. Görlach, R. P. Brandes, K. Nguyen, M. Amidi, F. Dehghani, R. Busse
Journal: Circulation Research (2000)

Abstract —Reactive oxygen species (ROS) play an important role in regulating vascular tone and intracellular signaling; the enzymes producing ROS in the vascular wall are, however, poorly characterized. We investigated whether a functionally active NADPH oxidase similar to the leukocyte enzyme, ie, containing the subunits p22phox and gp91phox, is expressed in endothelial cells (ECs) and smooth muscle cells (SMCs). Phorbol 12-myristate 13-acetate (PMA), a stimulus for leukocyte NADPH oxidase, increased ROS generation in cultured ECs and endothelium-intact rat aortic segments, but not in SMCs or endothelium-denuded arteries. NADPH enhanced chemiluminescence in all preparations. p22phox mRNA and protein was detected in ECs and SMCs, whereas the expression of gp91phox was confined to ECs. Endothelial gp91phox was identical to the leukocyte form as determined by sequence analysis. In contrast, mitogenic oxidase-1 (mox1) was expressed in SMCs, but not in ECs. To determine the functional relevance of gp91phox expression, experiments were performed in aortic segments from wild-type, gp91phox − /− , and endothelial NO synthase (eNOS) − /− mice. PMA-induced ROS generation was comparable in aortae from wild-type and eNOS − /− mice, but was attenuated in segments from gp91phox − /− mice. Endothelium-dependent relaxation was greater in aortae from gp91phox − /− than from wild-type mice. The ROS scavenger tiron increased endothelium-dependent relaxation in segments from wild-type, but not from gp91phox − /− mice. These data demonstrate that ECs, in contrast to SMCs, express a gp91phox-containing leukocyte-type NADPH oxidase. This enzyme is a major source for arterial ROS generation and affects the bioavailability of endothelium-derived NO. ( Circ Res. 2000;87:26-32.)
Regulation of interleukin 6 receptor expression in human monocytes and monocyte-derived macrophages. Comparison with the expression in human hepatocytes.
Authors: J Bauer, T M Bauer, T Kalb, T Taga, G Lengyel, T Hirano, T Kishimoto, G Acs, L Mayer, W Gerok
Journal: The Journal of Experimental Medicine (1989)

IL-6 is a cytokine with pleiotropic biological functions, including induction of the hepatic acute phase response and differentiation of activated B cells into Ig-secreting plasma cells. We found that human peripheral blood monocytes express the IL-6-R, which is undetectable on the large majority of lymphocytes of healthy individuals. Stimulation of monocytes by endotoxin or IL-1 causes a rapid downregulation of IL-6-R mRNA levels and a concomitant enhancement of IL-6 mRNA expression. IL-6 itself was found to suppress the IL-6-R at high concentrations. A gradual decrease of IL-6-R mRNA levels was observed along in vitro maturation of monocytes into macrophages. We show that downregulation of IL-6-R mRNA levels by IL-1 and IL-6 is monocyte specific, since IL-6-R expression is stimulated by both IL-1 and IL-6 in cultured human primary hepatocytes. Our data indicate that under noninflammatory conditions, monocytes may play a role in binding of trace amounts of circulating IL-6. Repression of monocytic IL-6-R and stimulation of hepatocytic IL-6-R synthesis may represent a shift of the IL-6 tissue targets under inflammatory conditions.
Rapid tissue engineering of biomimetic human corneal limbal crypts with 3D niche architecture
Authors: Hannah J. Levis, Isobel Massie, Marc A. Dziasko, Andreas Kaasi, Julie T. Daniels
Journal: Biomaterials (2013)

Limbal epithelial stem cells are responsible for the maintenance of the human corneal epithelium and these cells reside in a specialised stem cell niche. They are located at the base of limbal crypts, in a physically protected microenvironment in close proximity to a variety of neighbouring niche cells. Design and recreation of elements of various stem cell niches have allowed researchers to simplify aspects of these complex microenvironments for further study in vitro. We have developed a method to rapidly and reproducibly create bioengineered limbal crypts (BLCs) in a collagen construct using a simple one-step method. Liquid is removed from collagen hydrogels using hydrophilic porous absorbers (HPAs) that have custom moulded micro-ridges on the base. The resulting topography on the surface of the thin collagen constructs resembles the dimensions of the stromal crypts of the human limbus. Human limbal epithelial cells seeded onto the surface of the constructs populate these BLCs and form numerous layers with a high proportion of the cells lining the crypts expressing putative stem cell marker, p63α. The HPAs are produced using a moulding process that is flexible and can be adapted depending on the requirements of the end user. Creation of defined topographical features using this process could be applicable to numerous tissue-engineering applications where varied 3-dimensional niche architectures are required.
Childhood Obesity in Developing Countries: Epidemiology, Determinants, and Prevention
Authors: Nidhi Gupta, Kashish Goel, Priyali Shah, Anoop Misra
Journal: Endocrine Reviews (2012)

Rapidly changing dietary practices and a sedentary lifestyle have led to increasing prevalence of childhood obesity (5-19 yr) in developing countries recently: 41.8% in Mexico, 22.1% in Brazil, 22.0% in India, and 19.3% in Argentina. Moreover, secular trends indicate increasing prevalence rates in these countries: 4.1 to 13.9% in Brazil during 1974-1997, 12.2 to 15.6% in Thailand during 1991-1993, and 9.8 to 11.7% in India during 2006-2009. Important determinants of childhood obesity include high socioeconomic status, residence in metropolitan cities, female gender, unawareness and false beliefs about nutrition, marketing by transnational food companies, increasing academic stress, and poor facilities for physical activity. Childhood obesity has been associated with type 2 diabetes mellitus, the early-onset metabolic syndrome, subclinical inflammation, dyslipidemia, coronary artery diseases, and adulthood obesity. Therapeutic lifestyle changes and maintenance of regular physical activity through parental initiative and social support interventions are the most important strategies in managing childhood obesity. Also, high-risk screening and effective health educational programs are urgently needed in developing countries.
[Ca2+]i transient and contraction of isolated rat ventricular myocytes arenhanced by sera of patients treated with interferon α-2b
Authors: M. Petelenz, R. Janiak, J. Musialik, B. Lewartowski, W. Mazur, B. Strzałka, A. Miąsko, Z. Gonciarz
Journal: Journal of Hepatology (1998)
COPD prevalence is increased in lung cancer, independent of age, sex and smoking history
Authors: R. P. Young, R. J. Hopkins, T. Christmas, P. N. Black, P. Metcalf, G. D. Gamble
Journal: European Respiratory Journal (2009)

Chronic obstructive pulmonary disease (COPD) is a common comorbid disease in lung cancer, estimated to affect 40-70% of lung cancer patients, depending on diagnostic criteria. As smoking exposure is found in 85-90% of those diagnosed with either COPD or lung cancer, coexisting disease could merely reflect a shared smoking exposure. Potential confounding by age, sex and pack-yr smoking history, and/or by the possible effects of lung cancer on spirometry, may result in over-diagnosis of COPD prevalence. In the present study, the prevalence of COPD (pre-bronchodilator Global Initiative for Chronic Obstructive Lung Disease 2+ criteria) in patients diagnosed with lung cancer was 50% compared with 8% in a randomly recruited community control group, matched for age, sex and pack-yr smoking exposure (n = 602, odds ratio 11.6; p<0.0001). In a subgroup analysis of those with lung cancer and lung function measured prior to the diagnosis of lung cancer (n = 127), we found a nonsignificant increase in COPD prevalence following diagnosis (56-61%; p = 0.45). After controlling for important variables, the prevalence of COPD in newly diagnosed lung cancer cases was six-fold greater than in matched smokers; this is much greater than previously reported. We conclude that COPD is both a common and important independent risk factor for lung cancer.
Enzyme Replacement for Lysosomal Diseases
Authors: Roscoe O. Brady
Journal: Annual Review of Medicine (2005)

Following the demonstration of the nature of the enzymatic defects in the sphingolipid storage disorders in the mid-1960s, consideration was directed to the development of therapy for patients with these conditions. High on the list of possibilities was enzyme supplementation or replacement. Many years of arduous investigation and the development of novel protein targeting strategies were required to bring this concept to fruition. Enzyme replacement therapy (ERT) was eventually shown to be extraordinarily effective for patients with Gaucher disease, the most prevalent metabolic storage disorder of humans. Demonstration of the benefit of ERT in this disorder led to the extension of this approach to the treatment of other lysosomal storage disorders. This review presents the current status and anticipated developments in this field.
Predominant Role of T Cell Receptor (TCR)-α Chain in Forming Preimmune TCR Repertoire Revealed by Clonal TCR Reconstitution System
Authors: Tadashi Yokosuka, Kan Takase, Misao Suzuki, Yohko Nakagawa, Shinsuke Taki, Hidemi Takahashi, Takehiko Fujisawa, Hisashi Arase, Takashi Saito
Journal: The Journal of Experimental Medicine (2002)

The CDR3 regions of T cell receptor (TCR)-alpha and -beta chains play central roles in the recognition of antigen (Ag)-MHC complex. TCR repertoire is created on the basis of Ag recognition specificity by CDR3s. To analyze the potential spectrum of TCR-alpha and -beta to exhibit Ag specificity and generate TCR repertoire, we established hundreds of TCR transfectants bearing a single TCR-alpha or -beta chain derived from a cytotoxic T cell (CTL) clone, RT-1, specific for HIVgp160 peptide, and randomly picked up TCR-beta or -alpha chains. Surprisingly, one-third of such TCR-beta containing random CDR3 beta from naive T cells of normal mice could reconstitute the antigen-reactive TCR coupling with RT-1 TCR-alpha. A similar dominant function of TCR-alpha in forming Ag-specific TCR, though low-frequency, was obtained for lymphocytic choriomeningitis virus-specific TCR. Subsequently, we generated TCR-alpha and/or -beta transgenic (Tg) mice specific for HIVgp160 peptide, and analyzed the TCR repertoire of Ag-specific CTLs. Similar to the results from TCR reconstitution, TCR-alpha Tg generated CTLs with heterogeneous TCR-beta, whereas TCR-beta Tg-induced CTLs bearing a single TCR-alpha. These findings of Ag recognition with minimum involvement of CDR3 beta expand our understanding regarding the flexibility of the spectrum of TCR and suggest a predominant role of TCR-alpha chain in determining the preimmune repertoire of Ag-specific TCR.
Postprandial effects on twitch transdiaphragmatic pressure
Authors: W.D-C. Man, Y-M. Luo, N. Mustfa, G.F. Rafferty, J-C. Glerant, M.I. Polkey, J. Moxham
Journal: European Respiratory Journal (2002)

Twitch transdiaphragmatic pressure ( P di,tw ), measured following magnetic stimulation of the phrenic nerves, is used to assess diaphragm strength, contractility and fatigue. Although the effects of posture, lung volume and potentiation on P di,tw are well described, it is not known whether the degree of gastric filling affects the measurement. P di,tw was recorded in seven healthy volunteers on two occasions with antero-lateral magnetic stimulation of the phrenic nerves. On the first occasion, the subjects had fasted for at least 8 h, whilst on the second occasion, measurements were made after each subject had eaten a substantial meal sufficient to produce a feeling of satiation. Mean postprandial unpotentiated and potentiated P di,tw were significantly greater than corresponding fasting P di,tw in all seven volunteers (29.8 versus 25.7 cmH 2 O and 38.9 versus 34.4 cmH 2 O, respectively). This was due to a significantly increased gastric pressure component (1.10 versus 0.84 and 0.94 versus 0.78, respectively), and reduced abdominal compliance (36 versus 62 mL·cmH 2 O −1 ). Twitch oesophageal pressure was preserved (15.0 versus 15.4 cmH 2 O). The postprandial state increases twitch transdiaphragmatic pressure, and this should be taken into account when using twitch transdiaphragmatic pressure to follow-up patients or to assess the effects of interventions on diaphragm contractility.