tbuckley/cabot-search huggingface dataset:
Pretargeting of Carcinoembryonic Antigen–Expressing Cancers with a Trivalent Bispecific Fusion Protein Produced in Myeloma Cells
Authors: Edmund A. Rossi, Chien-Hsing Chang, Michele J. Losman, Robert M. Sharkey, Habibe Karacay, William McBride, Thomas M. Cardillo, Hans J. Hansen, Zhengxing Qu, Ivan D. Horak, David M. Goldenberg
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To characterize a novel trivalent bispecific fusion protein and evaluate its potential utility for pretargeted delivery of radionuclides to tumors. Experimental Design: hBS14, a recombinant fusion protein that binds bispecifically to carcinoembryonic antigen (CEA) and the hapten, histamine-succinyl-glycine (HSG), was produced by transgenic myeloma cells and purified to near homogeneity in a single step using a novel HSG-based affinity chromatography system. Biochemical characterization included size-exclusion high-performance liquid chromatography (SE-HPLC), SDS-PAGE, and isoelectric focusing. Functional characterization was provided by BIAcore and SE-HPLC. The efficacy of hBS14 for tumor pretargeting was evaluated in CEA-expressing GW-39 human colon tumor–bearing nude mice using a bivalent HSG hapten (IMP-241) labeled with 111In. Results: Biochemical analysis showed that single-step affinity chromatography provided highly purified material. SE-HPLC shows a single protein peak consistent with the predicted molecular size of hBS14. SDS-PAGE analysis shows only two polypeptide bands, which are consistent with the calculated molecular weights of the hBS14 polypeptides. BIAcore showed the bispecific binding properties and suggested that hBS14 possesses two functional CEA-binding sites. This was supported by SE-HPLC immunoreactivity experiments. All of the data suggest that the structure of hBS14 is an 80 kDa heterodimer with one HSG and two CEA binding sites. Pretargeting experiments in the mouse model showed high uptake of radiopeptide in the tumor, with favorable tumor-to-nontumor ratios as early as 3 hours postinjection. Conclusions: The results indicate that hBS14 is an attractive candidate for use in a variety of pretargeting applications, particularly tumor therapy with radionuclides and drugs.
Medical theories on the cause of death in crucifixion
Authors: M. W Maslen
Journal: Journal of the Royal Society of Medicine (2006)

I see crosses there, not just of one kind but made in many different ways: some have their victims with their head down to the ground, some impale their private parts, others stretch out their arms '. 4 In Roman times a common starting point was to be whipped across the back, buttocks and legs with a flagrum.
Disparity in Osmolarity-Induced Vascular Reactivity
Authors: El Rasheid Zakaria, C. Michelle Hunt, Na Li, Patrick D. Harris, R. Neal Garrison
Journal: Journal of the American Society of Nephrology (2005)

Conventional peritoneal dialysis solutions (PDS) are vasoactive. This study was conducted to identify vasoactive components of PDS and to describe quantitatively such vasoactivity. Anesthetized nonheparinized rats were monitored continuously for hemodynamics while the microvasculature of the jejunum was studied with in vivo intravital microscopy. In separate experiments, vascular reactivity of rat endothelium-intact and -denuded aortic rings (2 mm) was studied ex vivo in a standard tissue bath. In both studies, suffusion of the vessels was performed with filter-sterilized isotonic and hypertonic solutions that contained glucose or mannitol as osmotic agents. PDS served as a control (Delflex 2.25%). Hypertonic glucose and mannitol solutions produced a significant vascular reactivity in aortic rings and instantaneous and sustained vascular relaxation at all levels of the intestinal microvasculature. Similarly, lactate that was dissolved in a low-pH isotonic physiologic salt solution produced significant force generation in aortic rings. Whereas isotonic glucose and mannitol solutions had no vasoactivity in aortic rings, isotonic glucose produced a selective, insidious, and time-dependent vasodilation in the intestinal premucosal arterioles (18 +/- 0.2% of baseline), which was not observed in the larger inflow arterioles (100 mum). This isotonic glucose-mediated vascular relaxation can be attenuated by approximately 50% with combined adenosine A(2a) and A(2b) receptor antagonists and completely abolished by adenosine A(1) receptor inhibition. By using two different experimental techniques, this study demonstrates that hyperosmolality and lactate are the major vasoactive components of clinical peritoneal dialysis solutions. The pattern and the magnitude of such reactivity are dependent on vessel size and on the solutes' metabolic activity. Low pH of conventional PDS is not a vasoactive component by itself but renders lactate vasoactive. Energy-dependent transport of glucose into cells mediates vasodilation of small visceral arterioles by an adenosine receptor-mediated mechanism and constitutes a significant fraction of PDS-mediated vascular reactivity in the visceral microvasculature.
Vitamin A supplementation in preschool children and risk of hearing loss as adolescents and young adults in rural Nepal: randomised trial cohort follow-up study
Authors: J. Schmitz, K. P. West, S. K. Khatry, L. Wu, S. C. LeClerq, S. L. Karna, J. Katz, A. Sommer, J. Pillion
Journal: BMJ (2012)

<b>Objective</b> To determine whether vitamin A supplementation administered in the preschool years can lower the risk of hearing loss in adolescence and adulthood. <b>Design</b> Follow-up study of adolescents and young adults who, as preschool aged children in 1989, were enrolled into a cluster randomised, double blinded, placebo controlled trial of vitamin A supplementation. <b>Setting</b> South central, rural Nepal. <b>Participants</b> 2378 adolescents and young adults aged 14 to 23, representing 51% of those who finished the original trial and 71% of those living in the study area in 2006. <b>Interventions</b> Every four months for 16 months preschool children were visited at home, given an oral 200 000 IU dose of vitamin A (half dose at age 1-11 months, quarter dose at &lt;1 month) or placebo and the parents were queried about any childhood illnesses in the previous week, including purulent discharge from the ears. <b>Main outcome measures</b> Prevalence of mild or worse hearing loss (≥30 dB) in the most affected ear and tympanometric measures of middle ear function (peak height, ear canal volume, and gradient). <b>Results</b> During the original trial, the prevalence of middle ear infection during the preschool years did not differ between the supplement groups. By adolescence and early adulthood, a non-significant 17% reduction in hearing loss occurred among those who had periodically received vitamin A compared with placebo as preschool aged children (odds ratio 0.83, 95% confidence interval 0.62 to 1.12). Among participants with any ear discharge in early childhood, vitamin A supplementation was associated with a reduced risk of hearing loss, by 42% (0.58, 0.37 to 0.92) compared with controls, after adjusting the confidence interval for the design effect of the original trial. Abnormal tympanometric peak height of the middle ear system was less likely among participants supplemented with vitamin A in childhood. <b>Conclusion</b> In undernourished settings, periodic, high dose vitamin A supplementation may reduce the risk of hearing loss associated with purulent ear infections in early childhood.
Myelodysplastic syndromes in <scp>S</scp>outh <scp>A</scp>merica: A multinational study of 1080 patients
Authors: Carolina B. Belli, Ronald Feitosa Pinheiro, Yesica Bestach, Irene B. Larripa, Roberta Sandra da Silva Tanizawa, Graciela Alfonso, Jacqueline Gonzalez, Mariana Rosenhain, Nora Watman, Marcela Cavalcante de Andrade Silva, Pedro Negri Aranguren, Hernán García Rivello, Silvia M.M. Magalhaes, Ximena Valladares, María S. Undurraga, Elvira R.P. Velloso
Journal: American Journal of Hematology (2015)

There are previously reported data describing differences between Asian and European patients with Myelodysplastic Syndromes (MDS), few direct comparisons based on cancer registration characteristics or using cohorts to validate scoring systems. This is the first study from South-America, which attempts to describe demographic, clinical features, and outcome of MDS patients. We retrospectively analyzed 1,080 patients with de novo MDS from Argentina (635), Brazil (345), and Chile (100). Chilean patients were younger (P = 0.001) with female preponderance (P = 0.071). Brazilian series showed a higher predominance of RARS subtype regarding FAB and WHO classifications (P < 0.001). Hemoglobin levels were significantly lower in Brazilian and Chilean series (P < 0.001), and Chilean series also showed a lower platelet count (P = 0.028), with no differences concerning the neutrophil count, % BM blast, and the distribution of cytogenetic risk groups (P > 0.05). Chilean series depicted a lower overall survival (OS; 35 months vs. 56 months-Argentine; 55 months-Brazil, P = 0.030), which was consistent with a higher predominance of the high-risk group according both to the IPSS and IPSS-R (P = 0.046 and P < 0.001). The IPSS-R system and its variables showed a good reproducibility to predict clinical outcome for the whole South-American population. Epidemiological and clinical characteristics, distribution among prognostic subgroups, the OS, and the access to disease modifying therapies were more similar between Argentinean and Brazilian compared with Chilean MDS series. This will need further analysis in a larger group of patients. Descriptive and comparative studies are necessary to establish epidemiological features useful for public health attitudes to generate suitable therapeutic schemes.
TRANSGENIC MICE IN THE ANALYSIS OF METABOLIC REGULATION
Authors: Fatima Bosch, Anna Pujol, Alfons Valera
Journal: Annual Review of Nutrition (1998)

▪ Abstract In normal animals, the extracellular concentration of glucose is maintained within a very narrow range by the matching of glucose flux into and out of the extracellular space through the tightly coordinated secretion of insulin and glucagon. Functional alterations in β-cells, liver, or skeletal muscle and adipose tissue may disrupt glucose homeostasis and lead to the development of non–insulin-dependent diabetes mellitus (type 2 diabetes). This review outlines the contribution of these organs and tissues to the control of glucose homeostasis. We discuss new insights obtained through studies of transgenic mice that overexpress or show decreased expression of putative key genes in the regulation of pancreatic β-cell function, in the control of hepatic glucose uptake and output, and in the regulation of glucose uptake and utilization by skeletal muscle and adipose tissue.
Inhibition of lodinated Nerve Growth Factor Binding by the Suspected Tumor Promoters Saccharin and Cyclamate&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D N Ishii
Journal: JNCI Journal of the National Cancer Institute (1982)

The strong correlation between tumor-promoting activity and the capacity to inhibit nerve growth factor-induced neurite outgrowth for a number of compounds prompted studies on the suspected bladder tumor promoters saccharin and cyclamate. These artificial sweeteners reversibly inhibited neurite outgrowth and binding of [125I]nerve growth factor in embryonic chick sensory ganglia cells. Curves showing the dose-dependent inhibition of response and the dose-dependent inhibition of binding to high affinity sites were closely parallel. The inhibition appeared to be due to a reduction in the affinity rather than to a change in the number of binding sites, as indicated by the extent of reduction in the association rate. These results suggest that alteration of cellular differentiation by tumor promoters may result from interactions with receptor systems that regulate specialized cell functions.
Deficiency in AMPK attenuates ethanol-induced cardiac contractile dysfunction through inhibition of autophagosome formation
Authors: Rui Guo, Jun Ren
Journal: Cardiovascular Research (2012)

Binge drinking often triggers compromised myocardial contractile function while activating AMP-activated protein kinase (AMPK). Given the role of AMPK in the initiation of autophagy through the mammalian target of rapamycin complex 1 (mTORC1) and Unc51-like kinase (ULK1), this study was designed to examine the impact of AMPK deficiency on cardiac function and the mechanism involved with a focus on autophagy following an acute ethanol challenge. Wild-type (WT) and transgenic mice overexpressing a kinase-dead (KD) α2 isoform (K45R mutation) of AMPK were challenged with ethanol. Glucose tolerance, echocardiography, Langendorff heart and cardiomyocyte contractile function, autophagy, and autophagic signalling including AMPK, acetyl-CoA carboxylase (ACC), mTOR, the mTORC1-associated protein Raptor, and ULK1 were examined. Ethanol exposure triggered glucose intolerance and compromised cardiac contraction accompanied by increased phosphorylation of AMPK and ACC as well as autophagosome accumulation (increased LC3II and p62), the effects of which were attenuated or mitigated by AMPK deficiency or inhibition. Ethanol dampened and stimulated, respectively, the phosphorylation of mTOR and Raptor, the effects of which were abolished by AMPK deficiency. ULK1 phosphorylation at Ser757 and Ser777 was down-regulated and up-regulated, respectively, by ethanol, the effect of which was nullified by AMPK deficiency or inhibition. Moreover, the ethanol challenge enhanced LC3 puncta in H9c2 cells and promoted cardiac contractile dysfunction, and these effects were ablated by the inhibition of autophagy or AMPK. Lysosomal inhibition failed to accentuate ethanol-induced increases in LC3II and p62. In summary, these data suggest that ethanol exposure may trigger myocardial dysfunction through a mechanism associated with AMPK-mTORC1-ULK1-mediated autophagy.
Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial
Authors: Toshifusa Nakajima, Atsushi Nashimoto, Masatsugu Kitamura, Tsuyoshi Kito, Takeshi Iwanaga, Kenzo Okabayashi, M Sasaki, Masashi Goto
Journal: The Lancet (1999)
1032-129 By relieving obstruction, disopyramide increases extent and duration of systolic shortening in obstructive hypertrophic cardiomyopathy: A Doppler tissue imaging study
Authors: Shrikanth P Upadya, Ivan Barac, Vilma Casteneda, Michael Passick, Farooq A Chaudhry, Mark Sherrid
Journal: Journal of the American College of Cardiology (2004)
Training in large bowel cancer surgery
Authors: W. H Isbister, R J. Aitken
Journal: BMJ (1999)

Low dose aspirin for preventing and treating pre-eclampsia Author of editorial did not criticise studies' methodologyEditor-In her editorial discussing the value or otherwise of aspirin for preventing and treating pre-eclampsia Duley wonders why the small trials have such different results from the large trials. 1 We suggest the following answer.Evidence based medicine means integrating individual skill with the best available evidence from systematic research.Duley's conclusions, based on several multicentre studies, seem to rely on the conclusions of these studies without her making criticisms of the methodology used.Firstly, the timing of the start of treatment with low dose aspirin is important.The studies consistently fail to show the percentage of women who were < 16 weeks pregnant, the crucial time when maximum trophoblastic invasion is taking place (table ).This issue was raised by de Swiet in Bower's news article 2 and by Beaufilis et al. 3 Secondly, the dose of aspirin used in the later large trials is low.A meta-analysis by Leitich et al (not quoted in the editorial) shows that aspirin was more effective at higher doses (100-150 mg/day) than at lower doses (50-80 mg/day). 4It seems that these large studies have looked at the wrong dose of aspirin used at the wrong time of pregnancy.The editorial's conclusions are based on trials with flawed methodology.The question of whether aspirin given in early pregnancy in an appropriate dose is effective in preventing pre-eclampsia remains unanswered.
Genetically Mediated <i>Nf1</i> Loss in Mice Promotes Diverse Radiation-Induced Tumors Modeling Second Malignant Neoplasms
Authors: Grace Choi, Brian Huang, Emile Pinarbasi, Steve E. Braunstein, Andrew E. Horvai, Scott Kogan, Smita Bhatia, Bruce Faddegon, Jean L. Nakamura
Journal: Cancer Research (2012)

Abstract Second malignant neoplasms (SMN) are therapy-induced malignancies and a growing problem in cancer survivors, particularly survivors of childhood cancers. The lack of experimental models of SMNs has limited understanding of their pathogenesis. It is currently not possible to predict or prevent this devastating late complication. Individuals with neurofibromatosis I (NF1) are at increased risk of developing therapy-induced cancers for unclear reasons. To model SMNs, we replicated clinical radiotherapy and delivered fractionated abdominal irradiation to Nf1+/− and wild-type mice. Similar to irradiated cancer survivors, irradiated wild-type and Nf1+/− mice developed diverse in-field malignancies. In Nf1+/− mice, fractionated irradiation promoted both classical NF1-associated malignancies and malignancies unassociated with the NF1 syndrome but typical of SMNs. Nf1 heterozygosity potentiated the mutagenic effects of irradiation, as evidenced by the significantly reduced survival after irradiation and tumor development that was often characterized by synchronous primary tumors. Interestingly, diverse radiation-induced tumors arising in wild-type and Nf1+/− mice shared a genetic signature characterized by monoallelic loss of Nf1 and the adjacent Trp53 allele. These findings implicate Nf1 loss as mediating tumorigenesis in a broad range of cell types and organs extending beyond the classical NF1 tumor histologies. Examining clinical SMN samples, we found LOH of NF1 in SMNs from non-NF1 patients. Nf1 heterozygosity confers broad susceptibility to genotoxin-induced tumorigenesis, and this paradigm serves as an experimental platform for future studies of SMNs. Cancer Res; 72(24); 6425–34. ©2012 AACR.
Regulation of inflammatory responses by IL-17F
Authors: Xuexian O. Yang, Seon Hee Chang, Heon Park, Roza Nurieva, Bhavin Shah, Luis Acero, Yi-Hong Wang, Kimberly S. Schluns, Russell R. Broaddus, Zhou Zhu, Chen Dong
Journal: The Journal of Experimental Medicine (2008)

Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor–associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F–deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.
Health Care and Productivity Costs Associated With Diabetic Patients With Macrovascular Comorbid Conditions
Authors: Alex Z. Fu, Ying Qiu, Larry Radican, Brian J. Wells
Journal: Diabetes Care (2009)

OBJECTIVE To examine and quantify from the societal perspective the impact of macrovascular comorbid conditions (MVCCs) on health care and productivity costs in diabetic patients in the U.S. RESEARCH DESIGN AND METHODS With use of the pooled Medical Expenditure Panel Survey (MEPS) 2004 and 2006 data, a nationally representative adult sample (aged ≥18 years) was included in the study. Health care cost was measured by the annual health care expenditure. Productivity cost was calculated from the lost productivity from missed work days and additional bed days due to illness/injury based on the 2006 average national hourly wage. Both 2004 and 2006 cost data were adjusted to 2006 dollars. Given the heavily right-skewed distribution of the cost data, the generalized linear model with log-link function and γ variance was used to identify the relationship between MVCCs and costs after controlling for age, sex, race, ethnicity, education, income, employment status, smoking status, health insurance, diabetes severity, and comorbidities. Negative binomial models were applied to analyze the outcomes of missed work days and bed days. All statistics were adjusted using the proper sampling weight from MEPS. RESULTS Compared with diabetic patients without MVCCs (n = 3,320), those with MVCCs (n = 913) had statistically significant higher annual health care costs (5,120 USD, P &amp;lt; 0.001), more missed work days (13.03 days, P &amp;lt; 0.001), and more bed days (7.60 days, P = 0.025) per patient after controlling for differences in sociodemographics, smoking, diabetes severity, and comorbidities. The marginal lost productivity cost was 2,388 USD annually per patient. CONCLUSIONS From the U.S. societal perspective, MVCCs in diabetic patients are associated with increased health care and lost productivity costs.