tbuckley/cabot-search huggingface dataset:
P257 Human Cytomegalovirus Binding to Neutrophils Triggers a Pro-Survival Secretome That Modulates Monocyte Migration, Activation and Phenotype
Authors: M Reaves, D Storisteanu, M Wills, ER Chilvers, AS Cowburn
Journal: Thorax (2012)

Neutrophils provide the body’s first line of defence against invading pathogens. They respond to infection by releasing an array of chemokines, cytokines, and superoxide anions that initiate cascades of other immune mediators and cell types. Although the rapid response and flexibility of neutrophils make them an integral part of the body’s immune system, human cytomegalovirus (HCMV), paradoxically, may use neutrophil activation for its own evolutionary advantage. Here we report that human peripheral blood neutrophils exposed to a clinical strain of HCMV display a profound survival phenotype that occurs independent of viral gene expression. The initial HCMV driven survival response was partially dependent on ERK1/2 activation and profoundly inhibited by inhibition of NF-kB. Intriguingly, this initial survival event triggered by virus binding was augmented by a cytokine mediated effect whereby supernatants from infected neutrophils provided uninfected neutrophils with substantial protection against apoptosis – a protection which was PI3K as well as ERK1/2 and NF-kB dependent. Concomitant with a transferable survival effect the HCMV-neutrophil secretome also markedly manipulated autologous donor monocytes. Enhanced migration and subsequent differentiation to a permissive phenotype for HCMV infection was suggestive of a mechanism for efficient viral dissemination from the site of initial infection. Fascinatingly, although differentiation to a permissive phenotype was observed this was concomitant with down-regulation of a number of key activators of the adaptive immune response. Overall, these data illustrate the manipulation of an anti-viral response by a pathogen to enhance the outcome of infection which, intriguingly, involves a cell type not productively infected by the pathogen itself. These data further illustrate the complexity of pathogen interactions with the host immune system as well as providing new clues into the mechanisms HCMV exploits for efficient viral dissemination which could have implications on our understanding for HCMV pathogenesis.
Phase III Trial of Intraperitoneal Therapy With Yttrium-90–Labeled HMFG1 Murine Monoclonal Antibody in Patients With Epithelial Ovarian Cancer After a Surgically Defined Complete Remission
Authors: René H. Verheijen, Leon F. Massuger, Benedict B. Benigno, Agamemnon A. Epenetos, Alberto Lopes, John T. Soper, Janica Markowska, Rostislav Vyzula, Tom Jobling, Gordon Stamp, Gregory Spiegel, Dennis Thurston, Theo Falke, Joanna Lambert, Michael V. Seiden
Journal: Journal of Clinical Oncology (2006)

Purpose This was a multinational, open-label, randomized phase III trial comparing yttrium-90–labeled murine HMFG1 ( 90 Y-muHMFG1) plus standard treatment versus standard treatment alone in patients with epithelial ovarian cancer (EOC) who had attained a complete clinical remission after cytoreductive surgery and platinum-based chemotherapy. Patients and Methods In total, 844 International Federation of Gynecology and Obstetrics stage Ic to IV patients were initially screened, of whom 447 patients with a negative second-look laparoscopy (SLL) were randomly assigned to receive either a single dose of 90 Y-muHMFG1 plus standard treatment (224 patients) or standard treatment alone (223 patients). Patients in the active treatment arm received a single intraperitoneal dose of 25 mg of 90 Y-muHMFG1 (target dose 666 MBq/m 2 ). The primary end point was length of survival; secondary end points included time to relapse and safety. The study had an 80% power to detect a 15% change in survival. Results After a median follow-up of 3.5 years (range, 1 to 6 years), 70 patients had died in the active treatment arm compared with 61 patients in the control arm. Cox proportional hazards analysis of survival demonstrated no difference between treatment arms. In the study drug arm, 104 patients experienced relapse compared with 98 patients in the standard treatment arm. No difference in time to relapse was observed between the two study arms. Active therapy was associated with occasional grade 3 or 4 thrombocytopenia and neutropenia and grade 1 or 2 GI symptoms, abdominal discomfort, arthralgia, and myalgia. Conclusion A single IP administration of 90 Y-muHMFG1 to patients with EOC who had a negative SLL after primary therapy did not extend survival or time to relapse.
Autoantibody Profiles Reveal Ubiquilin 1 as a Humoral Immune Response Target in Lung Adenocarcinoma
Authors: Guoan Chen, Xiaoju Wang, Jianjun Yu, Sooryanarayana Varambally, Jindan Yu, Dafydd G. Thomas, Mu-Yen Lin, Prakash Vishnu, Zhuwen Wang, Rui Wang, Jeff Fielhauer, Debashis Ghosh, Thomas J. Giordano, Donald Giacherio, Andrew C. Chang, Mark B. Orringer, Talal El-Hefnawy, William L. Bigbee, David G. Beer, Arul M. Chinnaiyan
Journal: Cancer Research (2007)

Abstract There is considerable evidence that the presence of cancer can elicit a humoral immune response to specific proteins in the host, and these resulting autoantibodies may have potential as noninvasive biomarkers. To characterize the autoantibody repertoire present in the sera of patients with lung adenocarcinoma, we developed a high-density peptide microarray derived from biopanning a lung cancer phage display library. Using a 2,304-element microarray, we interrogated a total of 250 sera from Michigan lung cancer patients and noncancer controls to develop an “autoantibody profile” of lung adenocarcinoma. A set of 22 discriminating peptides derived from a training set of 125 serum samples from lung adenocarcinoma patients and control subjects was found to predict cancer status with 85% sensitivity and 86% specificity in an independent test set of 125 sera. Sequencing of the immunoreactive phage-peptide clones identified candidate humoral immune response targets in lung adenocarcinoma, including ubiquilin 1, a protein that regulates the degradation of several ubiquitin-dependent proteasome substrates. An independent validation set of 122 serum samples from Pittsburgh was examined using two overlapping clones of ubiquilin 1 that showed 0.79 and 0.74 of the area under the receiver operating characteristics curve, respectively. Significantly increased levels of both ubiquilin 1 mRNA and protein, as well as reduced levels of the phosphorylated form of this protein, were detected in lung tumors. Immunofluorescence using anti–ubiquilin 1 antibodies confirmed intracellular expression within tumors cells. These studies indicate that autoantibody profiles, as well as individual candidates, may be useful for the noninvasive detection of lung adenocarcinoma. [Cancer Res 2007;67(7):3461–7]
Factors contributing to parental decision-making in disclosing donor conception: a systematic review
Authors: A. Indekeu, K. Dierickx, P. Schotsmans, K.R. Daniels, P. Rober, T. D'Hooghe
Journal: Human Reproduction Update (2013)

BACKGROUNDIn recent years, changes in attitudes towards (non-)disclosure of donor conception to offspring and/or others have been observed. Studies have started to identify possible factors that contribute to these changes that are relevant for clinics, counsellors and policy-makers in their approach to the disclosure process. The aim of this systematic review was to integrate the existing knowledge on factors that influence the disclosure decision-making process of donor conception to offspring and/or others in heterosexual couples, and to discuss future trends and concerns.
Circadian rhythms in RA
Authors: M Cutolo, B Seriolo, C Craviotto, C Pizzorni, A Sulli
Journal: Annals of the Rheumatic Diseases (2003)

It is well known that some clinical signs and symptoms of rheumatoid arthritis (RA) vary within a day and between days, and the morning stiffness seen in patients with RA has become one of the diagnostic criteria of the disease (fig 1). 1 Among the clinical signs of joint inflammation in patients with RA, the intensity of pain changes consistently as a function of the hours of the day: pain is greater after waking up in the morning than in the afternoon or evening. 2 In patients with RA circadian variations are also found in joint swelling and finger size and these symptoms are in phase with the circadian rhythm of pain.The RA rhythms differ in phase by about 12 hours from the circadian changes of left and right hand grip strength: a greater grip strength is seen when joint circumferences and the subjective ratings of stiffness and pain are least and vice versa.
The inositol trisphosphate pathway mediates platelet-activating-factor-induced pulmonary oedema
Authors: R. Göggel, S. Uhlig
Journal: European Respiratory Journal (2005)

Platelet-activating factor (PAF) is a pro-inflammatory lipid mediator that increases vascular permeability by simultaneous activation of two pathways, one dependent on the cyclooxygenase metabolite prostaglandin E 2 and the other on the sphingomyelinase metabolite ceramide. The hypothesis that part of the PAF-induced oedema is mediated via the inositol 1,4,5-trisphosphate (IP 3 ) pathway or Rho kinase pathway was investigated. Oedema formation was induced in isolated perfused rat lungs by injection of 5 nmol PAF into the pulmonary artery. Lungs were pre-treated with specific inhibitors: edelfosine (L108) to block phosphatidyl-inositol-specific phospholipase C, xestospongin to block the IP 3 receptor, 5-iodonaphthalene-1-sulphonyl-homopiperazine (ML-7) to block myosin light chain kinase, and (+)- R -trans-4-(aminoethyl)- N -(4-pyridyl)cyclohexanecarboxamide (Y27632) to block Rho-associated protein kinase. Pre-treatment with L108 or xestospongin reduced PAF-induced oedema formation by 58 and 56%, respectively. The effect of L108 was additive to that of the cyclooxygenase inhibitor acetyl salicylic acid (88% oedema reduction). PAF-induced oedema formation was also reduced if extracellular calcium concentrations were lowered. Furthermore, treatment with ML-7 reduced oedema formation by 54%, whereas Y27632 was without effect. It is concluded that platelet-activating-factor-triggered oedema is mediated by activation of the inositol 1,4,5-trisphosphate pathway, influx of extracellular calcium and subsequent activation of a myosin light chain kinase-dependent and Rho-associated-protein-kinase-independent mechanism.
Increased expression of GDF-15 may mediate ICU-acquired weakness by down-regulating muscle microRNAs
Authors: S. A. A. Bloch, J. Y. Lee, T. Syburra, U. Rosendahl, M. J. D. Griffiths, P. R. Kemp, M. I. Polkey
Journal: Thorax (2014)

<h3>Rationale</h3> The molecular mechanisms underlying the muscle atrophy of intensive care unit-acquired weakness (ICUAW) are poorly understood. We hypothesised that increased circulating and muscle growth and differentiation factor-15 (GDF-15) causes atrophy in ICUAW by changing expression of key microRNAs. <h3>Objectives</h3> To investigate GDF-15 and microRNA expression in patients with ICUAW and to elucidate possible mechanisms by which they cause muscle atrophy in vivo and in vitro. <h3>Methods</h3> In an observational study, 20 patients with ICUAW and seven elective surgical patients (controls) underwent rectus femoris muscle biopsy and blood sampling. mRNA and microRNA expression of target genes were examined in muscle specimens and GDF-15 protein concentration quantified in plasma. The effects of GDF-15 on C2C12 myotubes in vitro were examined. <h3>Measurements and main results</h3> Compared with controls, GDF-15 protein was elevated in plasma (median 7239 vs 2454 pg/mL, p=0.001) and GDF-15 mRNA in the muscle (median twofold increase p=0.006) of patients with ICUAW. The expression of microRNAs involved in muscle homeostasis was significantly lower in the muscle of patients with ICUAW. GDF-15 treatment of C2C12 myotubes significantly elevated expression of muscle atrophy-related genes and down-regulated the expression of muscle microRNAs. miR-181a suppressed transforming growth factor-β (TGF-β) responses in C2C12 cells, suggesting increased sensitivity to TGF-β in ICUAW muscle. Consistent with this suggestion, nuclear phospho-small mothers against decapentaplegic (SMAD) 2/3 was increased in ICUAW muscle. <h3>Conclusions</h3> GDF-15 may increase sensitivity to TGF-β signalling by suppressing the expression of muscle microRNAs, thereby promoting muscle atrophy in ICUAW. This study identifies both GDF-15 and associated microRNA as potential therapeutic targets.
Growth Characteristics of MOPC-315 Plasmacytoma and Response to Anticancer Agents2, 3
Authors: Fred Valerlote, Richard Lynch, Nathan A. Berger, Evelyn White, Dean Coulter
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Growth Characteristics of MOPC-315 Plasmacytoma and Response to Anticancer Agents, Get access Fred Valerlote, Fred Valerlote Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Lynch, Richard Lynch Search for other works by this author on: Oxford Academic PubMed Google Scholar Nathan A. Berger, Nathan A. Berger Search for other works by this author on: Oxford Academic PubMed Google Scholar Evelyn White, Evelyn White Search for other works by this author on: Oxford Academic PubMed Google Scholar Dean Coulter Dean Coulter Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 66, Issue 6, June 1981, Pages 1083–1088, https://doi.org/10.1093/jnci/66.6.1083 Published: 01 June 1981 Article history Received: 06 June 1980 Accepted: 11 November 1980 Published: 01 June 1981
INORGANIC PHOSPHATE RESPONSE TO INTRAVENOUS GLUCOSE ADMINISTRATION IN PROGRESSIVE MUSCULAR DYSTROPHY
Authors: D. W. Van Bekkum, A. Querido
Journal: Journal of Clinical Investigation (1953)

One outstanding biochemical finding in progressive muscular dystrophy (P.M.D.) is excessive creatinuria. Much of the experimental work on the disease therefore has been centered on creatinecreatinine metabolism. The conclusion has now been reached that the creatinuria in this condition arises from a normal endogenous creatine production in the presence of impaired removal of creatine from the blood stream as a result of the severe diminution of muscle mass (1). It has been furthermore inferred that such parts of the muscles which survive, remove creatine at a normal rate. This decrease in functional muscle mass appears to be a common feature in all distinct cases of progressive muscular dystrophy. In view of the well established role of carbohydrates as a source of energy in muscular activity, it is surprising that until now hardly any evidence has become available of a disturbance of carbohydrate metabolism in P.M.D. Abnormalities in glucose metabolism have been reported, including hypoglycemia, by McCrudden and Sargent (2, 3), reduced sugar tolerance by Janney, Goodhart, and Isaacson (4), and increased utilization of glucose by Magee (5), but more careful studies by Shank, Gilder, and Hoagland failed to confirm these results (6). In evaluating these negative findings of oral and intravenous glucose tolerance studies, it should be kept in mind that in the process of the removal of glucose from the blood stream in fasting subjects, the capacity of the liver is probably large enough to compensate for any deficiency on the part of the musculature. However, a crude measure of the respectiye portions removed by these tissues seems to be possible by the simultaneous recording of inorganic serum phosphate during the glucose tolerance test. Pollack and his coworkers (7) have demonstrated that phosphate is removed from a glucose and phosphate-containing perfusion fluid by the isolated hind limb, but not by the isolated liver of the dog. Recently, the estimation of a blood glucose and inorganic phosphate curve, after an oral or intravenous glucose load, has been used for diagnostic purposes in diabetes mellitus, various forms of liver dysfunction and in the study of glucose resorption in tropical sprue (Forsham and Thorn [8], Volk and Lazarus [9], and Fourman [10]). In the present report, this method has been used in the study of five cases of P.M.D., and the results have been compared to those obtained in normal subjects.
The making of the ERJ: behind the scenes and Editors' cut
Authors: A.T. Dinh-Xuan, V. Brusasco
Journal: European Respiratory Journal (2010)

We began our editorship of the European Respiratory Journal ( ERJ ) 18 months ago, with the hope of serving the ERJ using modern communication media in order to advance respiratory medicine and its related biological and therapeutic research fields 1. Due to this, over the last 12 months a series of changes have been introduced to reshape the ERJ and meet the expectations and demands of our readers and fellow investigators worldwide 2. Now, at almost the mid-point of our mandate, whilst briefly looking back at the last 18 months, we want to continue to share with you information relating to the daily work procedure of the ERJ Editorial Office. In doing so, we hope to provide you with greater transparency, thereby bringing the ERJ not only closer to the eyes, but also the hearts and minds of its readership.

Quantitatively, the number of manuscripts submitted to the ERJ has risen steadily from around 1,500 per year in 2005 to more than 2,000 since 2008. We do not know whether this increase in submissions is the result, or the cause, of the increased impact factor of the ERJ 3, 4. However, what we do know is that the absolute number of manuscripts we have received from the day we began our editorship has already amounted to more than 3,000. Of these submitted manuscripts, 14% have received an immediate decision directly from the Chief Editors (without consulting the other members of the Editorial Board). Indeed, we have immediately accepted, mostly invited editorials and correspondences, or rejected manuscripts where the topics did not obviously fit with those of the …
Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts
Authors: Ritsuko Masuyama, Ingrid Stockmans, Sophie Torrekens, Riet Van Looveren, Christa Maes, Peter Carmeliet, Roger Bouillon, Geert Carmeliet
Journal: Journal of Clinical Investigation (2006)

Genomic actions induced by 1alpha25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] are crucial for normal bone metabolism, mainly because they regulate active intestinal calcium transport. To evaluate whether the vitamin D receptor (VDR) has a specific role in growth-plate development and endochondral bone formation, we investigated mice with conditional inactivation of VDR in chondrocytes. Growth-plate chondrocyte development was not affected by the lack of VDR. Yet vascular invasion was impaired, and osteoclast number was reduced in juvenile mice, resulting in increased trabecular bone mass. In vitro experiments confirmed that VDR signaling in chondrocytes directly regulated osteoclastogenesis by inducing receptor activator of NF-kappaB ligand (RANKL) expression. Remarkably, mineral homeostasis was also affected in chondrocyte-specific VDR-null mice, as serum phosphate and 1,25(OH)(2)D levels were increased in young mice, in whom growth-plate activity is important. Both in vivo and in vitro analysis indicated that VDR inactivation in chondrocytes reduced the expression of FGF23 by osteoblasts and consequently led to increased renal expression of 1alpha-hydroxylase and of sodium phosphate cotransporter type IIa. Taken together, our findings provide evidence that VDR signaling in chondrocytes is required for timely osteoclast formation during bone development and for the endocrine action of bone in phosphate homeostasis.
Impact of Body Mass Index and Weight Change After Treatment on Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From Cancer and Leukemia Group B 89803
Authors: Jeffrey A. Meyerhardt, Donna Niedzwiecki, Donna Hollis, Leonard B. Saltz, Robert J. Mayer, Heidi Nelson, Renaud Whittom, Alexander Hantel, James Thomas, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2008)

Purpose Obesity is a risk factor for the development of colon cancer. However, the influence of body mass index (BMI) on the outcome of patients with established colon cancer remains uncertain. Moreover, the impact of change in body habitus after diagnosis has not been studied. Patients and Methods We conducted a prospective, observational study of 1,053 patients who had stage III colon cancer and who were enrolled on a randomized trial of adjuvant chemotherapy. Patients reported on height and weight during and 6 months after adjuvant chemotherapy. Patients were observed for cancer recurrence or death. Results In this cohort of patients with stage III cancer, 35% of patients were overweight (BMI, 25 to 29.9 kg/m 2 ), and 34% were obese (BMI ≥ 30 kg/m 2 ). Increased BMI was not significantly associated with a higher risk of colon cancer recurrence or death (P trend = .54). Compared with normal-weight patients (BMI, 21 to 24.9 kg/m 2 ), the multivariate hazard ratio for disease-free survival was 1.00 (95% CI, 0.72 to 1.40) for patients with class I obesity (BMI, 30 to 34.9 kg/m 2 ) and 1.24 (95% CI, 0.84 to 1.83) for those with class II to III obesity (BMI ≥ 35 kg/m 2 ) after analysis was adjusted for tumor-related prognostic factors, physical activity, tobacco history, performance status, age, and sex. Similarly, after analysis was controlled for BMI, weight change (either loss or gain) during the time period between ongoing adjuvant therapy and 6 months after completion of therapy did not significantly impact on cancer recurrence and/or mortality. Conclusion Neither BMI nor weight change was significantly associated with an increased risk of cancer recurrence and death in patients with colon cancer.
Blood Pressure and Diabetic Nephropathy
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2010)

This is the fourth of a series of articles based on presentations at the American Diabetes Association Scientific Sessions held 5–9 June 2009 in New Orleans, Louisiana, pertaining to blood pressure and renal disease in diabetes.

### Diabetic nephropathy and obesity

At the Clinical Update in Diabetic Nephropathy at the American Diabetes Association Scientific Sessions, Karen A. Griffin (Maywood, IL) discussed interrelationships between obesity and the kidney, noting that obesity appears to be related to the increase in end-stage renal disease (ESRD), in part because of its relationship to diabetes and hypertension, but with a 1.2-to 1.6-fold increase in chronic kidney disease (CKD) risk even correcting for these associations. Reviewing CKD staging, in stages 3, 4, and 5, the glomerular filtration rate (GFR) is 30–59, 15–29, and <15 ml/min per 1.73 m2 BSA, respectively, and Griffin pointed out that the adjustment for body surface is quite important when considering the effect of body size. In a Kaiser Permanente analysis of 1,471 subjects developing ESRD in a 8,347,955 person-year follow-up, adjusted for age, sex, race, education, cigarette use, diabetes, blood pressure, lipids, and other variables, obesity increased the likelihood of ESRD with BMI ≥35 associated with a 5-fold increase, BMI 30–34.9 associated with a 3-fold increase, and BMI 25–29.9 associated with a 1.5-fold increase in risk (1). There are a number of different forms of obesity-related CKD, with the majority of cases associated with microalbuminuria, endothelial dysfunction, and mild-to-moderate decrease in GFR, mainly associated with cardiovascular risk. Coexistent obesity and CKD lead, however, to accelerated progression of the latter (2,3). A form of glomerulopathy occurs with obesity characterized by glomerular enlargement (which is more common in obesity) and focal segmental glomerulosclerosis (4). The pathogenesis may involve hyperfiltration, leading to glomerular capillary injury and sclerosis, in a fashion similar to occurring experimentally with 5/6 …