tbuckley/cabot-search huggingface dataset:
Longitudinal Changes in Body Mass and Composition in Survivors of Childhood Hematologic Malignancies After Allogeneic Hematopoietic Stem-Cell Transplantation
Authors: Hiroto Inaba, Jie Yang, Sue C. Kaste, Christine M. Hartford, Megan S. Motosue, Wassim Chemaitilly, Brandon M. Triplett, David R. Shook, Ching-Hon Pui, Wing Leung
Journal: Journal of Clinical Oncology (2012)

To measure longitudinal changes in body mass and composition in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem-cell transplantation (HSCT).Body mass index (BMI) was analyzed in 179 survivors by category (underweight, healthy-weight, overweight, and obese) and by z score. Fat and lean body mass measured by dual-energy x-ray absorptiometry was analyzed as z scores.Over a median 6.6 years of follow-up, BMI z scores diminished significantly (0.32 pre-HSCT v -0.60 at 10 years post-HSCT; P < .001). Mean z scores for fat mass stayed within population norms, but those for lean mass remained below normal levels and diminished significantly over time (P = .018). Pre-HSCT BMI category and/or z score were strongly predictive of post-HSCT BMI (P < .001) and of fat and lean mass z scores (both P < .001). Survivors with extensive chronic graft-versus-host disease were more likely than others to have low BMI (P = .004) and low lean mass (P < .001) post-HSCT. Older age at HSCT (P = .015) and T-cell-depleted graft (P = .018) were predictive of lower post-HSCT BMI. Female patients had higher body fat (P = .002) and lower lean mass (P = .013) z scores than male patients, and black patients had higher fat mass z scores than white patients (P = .026).BMI declines significantly after allogeneic HSCT for childhood hematologic malignancies, reflecting primarily a substantial decrease in lean mass but not fat mass. Monitoring and preservation of BMI and lean mass are vital, especially in those with the identified risk factors.
XBP-1 specifically promotes IgM synthesis and secretion, but is dispensable for degradation of glycoproteins in primary B cells
Authors: Boaz Tirosh, Neal N. Iwakoshi, Laurie H. Glimcher, Hidde L. Ploegh
Journal: The Journal of Experimental Medicine (2005)

Differentiation of B cells into plasma cells requires X-box binding protein-1 (XBP-1). In the absence of XBP-1, B cells develop normally, but very little immunoglobulin is secreted. XBP-1 controls the expression of a large set of genes whose products participate in expansion of the endoplasmic reticulum (ER) and in protein trafficking. We define a new role for XBP-1 in exerting selective translational control over high and sustained levels of immunoglobulin M (IgM) synthesis. XBP-1(-/-) and XBP-1(+/+) primary B cells synthesize IgM at comparable levels at the onset of stimulation with lipopolysaccharide or CpG. However, later there is a profound depression in synthesis of IgM in XBP-1(-/-) B cells, notwithstanding similar levels of micromRNA. In marked contrast, lack of XBP-1 does not affect synthesis and trafficking of other glycoproteins, or of immunoglobulin light chains. Contrary to expectation, degradation of proteins from the ER, using TCRalpha or US11-mediated degradation of class I major histocompatibility complex molecules as substrates, is normal in XBP-1(-/-) B cells. Furthermore, degradation of membrane mu was unaffected by enforced expression of XBP-1. We conclude that in primary B cells, the XBP-1 pathway promotes synthesis and secretion of IgM, but does not seem to be involved in the degradation of ER proteins, including that of mu chains themselves.
Sensitization of Individual Vascular Territories to the Antiphlogistic Effect of Hydrocortisone
Authors: HANS SELYE
Journal: Circulation Research (1954)

Experimental interference with the circulation in a circumscribed tissue area, too slight to produce any manifest disturbance in itself, can strikingly alter topical reactivity to irritants and to the antiphlogistic effect of hydrocortisone. Thus, certain vascular territories can be "selectively conditioned" to the anti-inflammatory actions of blood-borne corticoids. Conversely, when tissue damage is severe, such "selective conditioning" may induce a seemingly paradoxic reversal of the hydrocortisone effect, so that the hormone enhances inflammation. Here, impairment of circulation and hydrocortisone facilitate the production by irritants of necrosis, more than of inflammation. The resulting wide-spread necrosis induces an even greater inflammatory response, despite hydrocortisone, than would have been observed without hormone treatment.
Vitamin D concentrations in Asian children aged 2 years living in England: population survey
Authors: M. Lawson, M. Thomas
Journal: BMJ (1999)

The Social Survey Division of the Office for National Statistics on behalf of the Department of Health carried out a survey between 1994 and 1996 of infant feeding practices of mothers of Bangladeshi, Indian, or Pakistani origin living in England. 1 A blood sample was taken during October-November 1996 from a subsample of children aged 2 years for analysis of iron and 25-hydroxycholecalciferol (vitamin D) concentrations.Details for iron concentration are published elsewhere. 1 2We here report the vitamin D concentration.
The drug and vaccine landscape for neglected diseases (2000–11): a systematic assessment
Authors: Belen Pedrique, Nathalie Strub-Wourgaft, Claudette Some, Piero Olliaro, Patrice Trouiller, Nathan Ford, Bernard Pécoul, Jean-Hervé Bradol
Journal: The Lancet Global Health (2013)

In 1975-99, only 1·1% of new therapeutic products had been developed for neglected diseases. Since then, several public and private initiatives have attempted to mitigate this imbalance. We analysed the research and development pipeline of drugs and vaccines for neglected diseases from 2000 to 2011.We searched databases of drug regulatory authorities, WHO, and clinical trial registries for entries made between Jan 1, 2000, and Dec 31, 2011. We defined neglected diseases as malaria, tuberculosis, diarrhoeal diseases, neglected tropical diseases (NTDs; WHO definition), and other diseases of poverty according to common definitions.Of the 850 new therapeutic products registered in 2000-11, 37 (4%) were indicated for neglected diseases, comprising 25 products with a new indication or formulation and eight vaccines or biological products. Only four new chemical entities were approved for neglected diseases (three for malaria, one for diarrhoeal disease), accounting for 1% of the 336 new chemical entities approved during the study period. Of 148,445 clinical trials registered in Dec 31, 2011, only 2016 (1%) were for neglected diseases.Our findings show a persistent insufficiency in drug and vaccine development for neglected diseases. Nevertheless, these and other data show a slight improvement during the past 12 years in new therapeutics development and registration. However, for many neglected diseases, new therapeutic products urgently need to be developed and delivered to improve control and potentially achieve elimination.None.
Expression of MDA-7/IL-24 and Its Clinical Significance in Resected Non–Small Cell Lung Cancer
Authors: Shinya Ishikawa, Tatsuo Nakagawa, Ryo Miyahara, Yozo Kawano, Kazumasa Takenaka, Kazuhiro Yanagihara, Yosuke Otake, Hiromichi Katakura, Hiromi Wada, Fumihiro Tanaka
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin (IL)-24, is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells including lung cancer cells. However, only one clinical study has documented that MDA-7/IL-24 expression is down-regulated with progression of melanoma. Thus, the present study was conducted to assess the clinical significance of MDA-7/IL-24 expression in non–small cell lung cancer. Experimental Design: A total of 183 consecutive patients with resected pathologic stage I-IIIA, non–small cell lung cancer were retrospectively reviewed, and immunohistochemical staining was used to detect MDA-7/IL-24 expression. Results: MDA-7/IL-24 expression was high in 97 (53.0%) patients and low in the other patients. There was no significant correlation between MDA-7/IL-24 status and any patients' characteristic including pathologic stage. There was no significant difference in tumor angiogenesis or proliferative activity according to MDA-7/IL-24 status, but MDA-7/IL-24-high adenocarcinoma showed a significantly higher incidence of apoptotic tumor cell death than MDA-7/IL-24-low adenocarcinoma. MDA-7/IL-24-high patients seemed to show a favorable postoperative prognosis as compared with MDA-7/IL-24-low patients (5-year survival rates, 75.9% and 62.0%, respectively), although the difference did not reach a statistical significance (P = 0.061). Subset analyses showed that positive MDA-7/IL-24 expression was a significant factor to predict a favorable prognosis in adenocarcinoma (P = 0.033), which was confirmed by a multivariate analysis; there was no difference in the prognosis according to MDA-7/IL-24 status in squamous cell carcinoma. Conclusions: MDA-7/IL-24 status was a significant prognostic factor in lung adenocarcinoma, not in lung squamous cell carcinoma.
Demographic Signatures Accompanying the Evolution of Selfing in Leavenworthia alabamica
Authors: J. W. Busch, S. Joly, D. J. Schoen
Journal: Molecular Biology and Evolution (2011)

The evolution of selfing from outcrossing is a common transition, yet little is known about the mutations and selective factors that promote this shift. In the mustard family, single-locus self-incompatibility (SI) enforces outcrossing. In this study, we test whether mutations causing self-compatibility (SC) are linked to the self-incompatibility locus (S-locus) in Leavenworthia alabamica, a species where two selfing races (a2 and a4) co-occur with outcrossing populations. We also infer the ecological circumstances associated with origins of selfing using molecular sequence data. Genealogical reconstruction of the Lal2 locus, the putative ortholog of the SRK locus, showed that both selfing races are fixed for one of two different S-linked Lal2 sequences, whereas outcrossing populations harbor many S-alleles. Hybrid crosses demonstrated that S-linked mutations cause SC in each selfing race. These results strongly suggest two origins of selfing in this species, a result supported by population admixture analysis of 16 microsatellite loci and by a population tree built from eight nuclear loci. One selfing race (a4) shows signs of a severe population bottleneck, suggesting that reproductive assurance might have caused the evolution of selfing in this case. In contrast, the population size of race a2 cannot be distinguished from that of outcrossing populations after correcting for differences in selfing rates. Coalescent-based analyses suggest a relatively old origin of selfing in the a4 race (∼150 ka ago), whereas selfing evolved recently in the a2 race (∼12–48 ka ago). These results imply that S-locus mutations have triggered two recent shifts to selfing in L. alabamica, but that these transitions are not always associated with a severe population bottleneck, suggesting that factors other than reproductive assurance may play a role in its evolution.
High-dose chemotherapy with autologous bone marrow transplantation for the treatment of metastatic breast cancer.
Authors: D M Eddy
Journal: Journal of Clinical Oncology (1992)

PURPOSE This review was undertaken to examine the evidence of effectiveness of high-dose chemotherapy and autologous bone marrow transplantation (HDC/ABMT) for the treatment of metastatic breast cancer and to compare the magnitudes of the benefits and harms of HDC/ABMT with those of conventional doses of chemotherapy. DESIGN Published studies were reviewed and analyzed. RESULTS No randomized controlled trials have been published that evaluate HDC/ABMT. Only one internally controlled study has been conducted; it demonstrated that HDC/ABMT and conventional treatment have virtually identical outcomes. Comparisons of uncontrolled clinical series are confounded by patient selection and other biases. Gross comparisons indicate that, compared with conventional-dose chemotherapy, HDC/ABMT achieves (1) higher complete response rates (36% v 8%), (2) higher overall response rates (70% v 39%), (3) similar median response durations (8 months v 9.6 months), (4) similar median survival durations (16 months v 16.6 months), and (5) similar overall survival rates (eg, 43% 2-year survival v 39%). Observations of cases with longer-term disease-free survival are promising but not conclusive. High-dose chemotherapy with ABMT has a higher treatment-related mortality rate (5% to 15% v 1%), a high rate of nonmortal toxicity (approximately 30%), and a high rate of side effects (approaching 100%). CONCLUSIONS Firm conclusions are not possible because of the lack of controlled studies and the presence of numerous biases. However, the existing evidence does not demonstrate that HDC/ABMT is superior to conventional-dose chemotherapy for the treatment of metastatic breast cancer. Randomized controlled trials are needed.
Is It Time to Introduce HPV Self-Sampling for Primary Cervical Cancer Screening?
Authors: P. Petignat, P. Vassilakos
Journal: JNCI Journal of the National Cancer Institute (2012)

Regular Papanicolaou (Pap) testing has been the backbone of the most successful cancer reduction program in the public health system. However, it is not perfect. In high-income countries, more than half of the women who are diagnosed with cervical cancer had never had a Pap test or were infrequently screened (1). In the United Kingdom, recent studies have suggested a decline in the routine screening program participation to below its target rate of 80%, particularly among women aged 25–29 years (2). Factors that may discourage women from going for regular screening are lack of time, discomfort, inconvenience, cultural objections, and poor socioeconomic status. In low-resource regions, additional barriers include lack of knowledge and lack of accessible or appropriate screening facilities as well as the prohibitively high cost of screening. Offering a simple, inexpensive, and convenient self-test that respects individual privacy may improve the participation of women who might be otherwise reluctant to undergo screening and those who live in areas with poor access to health care. In the last few years, we have learned that self-collected vaginal specimens from women who have received appropriate instruction produce human papillomavirus (HPV) test results similar to cervical specimens collected by health-care professionals (3). This congruence has supported the concept of introducing HPV selfsampling (Self-HPV) as an alternative means for cervical cancer screening. However, screening is a complex process, and the introduction of a new screening scenario should be carefully evaluated. Fundamental issues that must be addressed regarding the future of Self-HPV as a primary screening method are 1) whether the performance for the detection of cervical intraepithelial neoplasia (CIN) grade 2–3 and cervical cancer (CIN2+) by Self-HPV is (at least) equal or superior to that of the Pap test, 2) whether screening participation rate with Self-HPV will be sufficiently high, and 3) whether comparable results would be obtained outside a research setting.
Hospitalisations and surgery in Crohn's disease
Authors: Charles N Bernstein, Edward V Loftus, Siew C Ng, Peter L Lakatos, Bjorn Moum
Journal: Gut (2012)

Hospitalisation and surgery are considered to be markers of more severe disease in Crohn's disease. These are costly events and limiting these costs has emerged as one rationale for the cost of expensive biologic therapies. The authors sought to review the most recent international literature to estimate current hospitalisation and surgery rates for Crohn's disease and place them in the historical context of where they have been, whether they have changed over time, and to compare these rates across different jurisdictions. It is in this context that the authors could set the stage for interpreting some of the early data and studies that will be forthcoming on rates of hospitalisation and surgery in an era of more aggressive biologic therapy. The most recent data from Canada, the United Kingdom and Hungary all suggest that surgical rates were falling prior to the advent of biologic therapy, and continue to fall during this treatment era. The impact of biologic therapy on surgical rates will have to be analysed in the context of evolving reductions in developed regions before biologic therapy was even introduced. Whether more aggressive medical therapy will decrease the requirement for surgery over long periods of time remains to be proven.
Association between type of training and risk of asthma in elite athletes
Authors: I. J. Helenius, H. O. Tikkanen, T. Haahtela
Journal: Thorax (1997)

BACKGROUND: Intensive endurance training has been associated with a high prevalence of symptoms compatible with asthma in elite athletes. It is not known, however, whether there is an association between the type of training for competitive events and the risk of asthma in highly trained athletes. METHODS: Two hundred and thirteen track and field athletes, mostly from Finnish national teams, and 124 controls of the same age completed a respiratory symptom questionnaire. Positive answers to physician diagnosed asthma were confirmed by personal interviews. The athletes were divided into two groups depending on whether they were speed and power athletes (n = 106) or long distance runners (n = 107). RESULTS: According to a logistic regression model the prevalence of physician diagnosed asthma was not associated with age, sex, or a family history of asthma. Long distance runners (OR 6.7; 95% CI 2.1 to 22.1) and speed and power athletes (OR 3.2; 95% CI 0.90 to 11.4) had a higher prevalence of physician diagnosed asthma than control subjects. Physician diagnosed asthma was found in 18 of 107 long distance runners (17%), in nine of 106 speed and power athletes (8%; p = 0.07 (chi 2 test)), and in four of 124 controls (3%; p &lt; 0.0004 (chi 2 test for trend)). CONCLUSIONS: The prevalence of physician diagnosed asthma is high in elite athletes and an association with the competitive event is suggested with long distance runners having a greater risk of developing asthma than speed and power athletes. This may be due to prolonged hyperventilation and increased exposure to inhalant allergens and irritants during endurance training and competition.
Hepatocellular carcinoma in hemophilia
Authors: M. Colombo, P. M. Mannucci, Doreen B. Brettler, A. Girolami, E. C. Y. Lian, F. Rodeghiero, Inge Scharrer, P. S. Smith, G. C. White
Journal: American Journal of Hematology (1991)

Abstract A questionnaire‐based survey Involving 11,801 hemophiliacs from 54 hemophilia centers in the USA and Europe documented the occurrence of hepatocellular carcinoma(HCC) in 10 patients. The crude rate of HCC was 3.2/100,000 patients/year, at least 30 times higher than the background incidence of this tumor in the countries of origin of the patients. All patients were Caucasians with hemophilia A, 39 to 74 years of age, and had liver cirrhosis. All had one or more risk factor for cirrhosis and HCC: 5 were positive for serum hepatitis B surface antigen, 4 had the antibody to hepatitis C virus, and 4 had histories of alcohol abuse. Serum alpha‐fetoprotein, measured in 6 patients, was significantly elevated in 4 (range: 807‐1399 ng/ml), and only moderately elevated in 2 (25 and 171 ng/ml). The onset of HCC was asymptomatic in 5 patients, whereas it was accompanied by jaundice, abdominal pain, or ascites in the remaining patients. Thus, HCC seems to be a more important secondary disease for hemophiliacs than formerly recognized. Since HCC is often asymptomatic, screening hemophiliacs with chronic liver disease with periodic ultrasound scans might increase the chances of detecting HCC at a stage amenable to surgical treatment.
Nebulized versus intravenous albuterol in hypercapnic acute asthma. A multicenter, double-blind, randomized study.
Authors: S Salmeron, L Brochard, H Mal, A Tenaillon, M Henry-Amar, D Renon, P Duroux, G Simonneau
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

In a multicenter, randomized, double-blind study, we compared the effects of nebulized (5 mg x 2) and intravenous (0.5 mg) albuterol (salbutamol) over 1 h in 47 patients admitted to hospital with severe acute asthma defined as a peak expiratory flow (PEF) below 150 L/min and hypercapnia (Pa(CO2) > or = 40 mm Hg). Additional treatment included nasal oxygen and hydrocortisone succinate. The efficacy was assessed after 1 h. In the group treated by nebulization (NEB group, n = 22) 19 (86%) patients (95% confidence interval: 65 to 97%) had been treated successfully according to predefined criteria, versus 12 (48%) patients (95% confidence interval: 28 to 69%) in the intravenously treated group (i.v. group, n = 25), p = 0.006. The mean increase in PEF was greater in the NEB group than in the i.v. group (+107 +/- 94 L/min versus +42 +/- 66 L/min, p = 0.01) as well as the decrease in Pa(CO2) values (-10 +/- 5 mm Hg versus -2 +/- 12 mm Hg, p < 0.01). Beta agonist-induced hypokalemia was more pronounced in the i.v. group than in the NEB group. We conclude that, in hypercapnic acute asthma, the nebulized route has a greater efficacy and fewer side effects than the intravenous route.
18FDG-PET Predicts Pharmacodynamic Response to OSI-906, a Dual IGF-1R/IR Inhibitor, in Preclinical Mouse Models of Lung Cancer
Authors: Eliot T. McKinley, Joseph E. Bugaj, Ping Zhao, Saffet Guleryuz, Christine Mantis, Prafulla C. Gokhale, Robert Wild, H. Charles Manning
Journal: Clinical Cancer Research (2011)

Abstract Purpose: To evaluate 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography imaging (18FDG-PET) as a predictive, noninvasive, pharmacodynamic (PD) biomarker of response following administration of a small-molecule insulin-like growth factor-1 receptor and insulin receptor (IGF-1R/IR) inhibitor, OSI-906. Experimental Design: In vitro uptake studies of 3H-2-deoxy glucose following OSI-906 exposure were conducted evaluating correlation of dose with inhibition of IGF-1R/IR as well as markers of downstream pathways and glucose metabolism. Similarly, in vivo PD effects were evaluated in human tumor cell line xenografts propagated in athymic nude mice by 18FDG-PET at 2, 4, and 24 hours following a single treatment of OSI-906 for the correlation of inhibition of receptor targets and downstream markers. Results: Uptake of 3H-2-deoxy glucose and 18FDG was significantly diminished following OSI-906 exposure in sensitive tumor cells and subcutaneous xenografts (NCI-H292) but not in an insensitive model lacking IGF-1R expression (NCI-H441). Diminished PD 18FDG-PET, collected immediately following the initial treatment agreed with inhibition of pIGF-1R/pIR, reduced PI3K (phosphoinositide 3-kinase) and MAPK (mitogen activated protein kinase) pathway activity, and predicted tumor growth arrest as measured by high-resolution ultrasound imaging. Conclusion: 18FDG-PET seems to serve as a rapid, noninvasive PD marker of IGF-1R/IR inhibition following a single dose of OSI-906 and should be explored clinically as a predictive clinical biomarker in patients undergoing IGF-1R/IR–directed cancer therapy. Clin Cancer Res; 17(10); 3332–40. ©2011 AACR.