tbuckley/cabot-search huggingface dataset:
Effect of Hematocrit and Inertial Losses on Pressure-Flow Relations in the Isolated Hindpaw of the Dog
Authors: ANTHONY M. BENIS, SHUNICHI USAMI, SHU CHIEN
Journal: Circulation Research (1970)

The effect of hematocrit on pressure-flow relations was studied in the perfused isolated hindpaw of the dog. Blood and suspensions of erythrocytes (RBC) in albumin-Ringer solution, hematocrit range of 0 to 80%, were used as perfusates. Flow resistance was found to increase markedly with hematocrit. No significant difference was found between pressure-flow data obtained with blood and RBC in albumin-Ringer solution when comparisons were made at comparable hematocrits, indicating negligible effect of RBC aggregation when blood was the perfusion fluid. Computations of flow resistance relative to cellfree perfusate indicated that non-Newtonian viscosity, as well as vessel distensibility, contributed to the nonlinearity of pressure-flow curves. Perfusion of paws with two Newtonian fluids of different viscosities allowed computation of inertial pressure losses under conditions of steady flow. At physiological perfusion pressures, inertial losses accounted for about 40% of the total pressure drop for cell-free albumin-Ringer solution, and dropped to about 5% for a hematocrit of 50. The results suggest that inertial losses, rather than a Fåhraeus-Lindqvist effect, play an important role in pressure-flow relations in the hindpaw.
Effect of Dietary Protein on the Response of Rainbow Trout ( Salmo gairdneri ) to Aflatoxin B 1 2 3
Authors: D. J. Lee, R. O. Sinnhuber, J. H. Wales, G. B. Putnam
Journal: JNCI Journal of the National Cancer Institute (1978)

Diets containing either 49.5% or 32% casein or fish protein concentrate (FPC) were fed to young rainbow trout (Salmo gairdneri) for 12 months. Five levels [0, 2, 6, 18, and 54 parts per billion (ppb)] of aflatoxin B1 (AFB1) were given in each of four different diets. A 30-fish sample was taken at 6, 9, and 12 months to determine the influence of diet on the carcinogenicity of AFB1. Both levels of casein produced similar hepatoma incidences at each level of AFB1. The diet high in FPC produced more tumours than did the casein diets at 2, 6, and 18 ppb AFB1, whereas fish fed the diet low in FPC had a significantly (P less than 0.05) lower hepatoma incidence than did the other three groups. The liver size (percent body wt) was smaller at higher toxin levels in all instances. The growth of fish given 32% casein was less than that of the other groups.
Randomized Phase II Study Comparing Two Schedules of Everolimus in Patients With Recurrent/Metastatic Breast Cancer: NCIC Clinical Trials Group IND.163
Authors: Susan L. Ellard, Mark Clemons, Karen A. Gelmon, Brian Norris, Hagen Kennecke, Stephen Chia, Kathleen Pritchard, Andrea Eisen, Ted Vandenberg, Marianne Taylor, Eric Sauerbrei, Moshe Mishaeli, David Huntsman, Wendy Walsh, Martin Olivo, Lynn McIntosh, Lesley Seymour
Journal: Journal of Clinical Oncology (2009)

Purpose To evaluate the safety and efficacy of oral everolimus, a mammalian target of rapamycin (mTOR) inhibitor, in two different schedules in minimally pretreated patients with metastatic breast cancer and to explore for possible biologic correlates of response. Patients and Methods Patients who received no or one prior chemotherapy regimen for metastatic breast cancer were entered onto this multicenter, noncomparative, randomized phase II study of everolimus 10 mg daily versus 70 mg weekly; the multinomial end points of response and progression were evaluated at 8 weeks. A two-stage accrual design was used, with 15 evaluable patients in each schedule in stage 1. Only daily therapy met criteria for continuing, and another 15 patients were added. pAKT, PTEN, carbonic anhydrase 9, estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were evaluated for possible correlation with response. Results The most common drug-related toxicities were fatigue, rash, anorexia, diarrhea, stomatitis, cough, and pneumonitis. Pneumonitis occurred at higher than expected rates and seemed to be schedule dependent, with the highest incidence on the daily schedule. Response rate with daily therapy was 12% (95% CI, 3.4% to 28.2%) compared with 0% (95% CI, 0.0% to 20.6%) for weekly therapy. Twenty-seven percent of patients on daily therapy discontinued treatment compared with 13% on weekly therapy (16% v 6% with pneumonitis, respectively). No biologic correlates of response could be identified, although there were trends favoring benefit in ER-positive and HER2-negative metastatic breast cancer. Conclusion Oral everolimus has activity in metastatic breast cancer that is schedule dependent. Daily therapy with 10 mg is worthy of further study in this patient population.
Homelessness and health: what can be done in general practice?
Authors: N. M J Wright, C. N E Tompkins, N. S Oldham, D. J Kay
Journal: Journal of the Royal Society of Medicine (2004)

In England between January and March 2003, 31 470 households were newly accepted by local authorities as homeless.1 The large and increasing numbers of people so categorized have complex health, social and psychological needs, and in the past decade numerous centres have been established to provide primary care to homeless populations.2 Personal medical services legislation has made this possible; previously, the system of general practitioner (GP) fundholding was an obstacle to primary care for homeless people with complex problems.3 The new nationally enhanced GP contract will probably offer incentives for care of homeless people.4

What are the existing barriers for this group? In a report to the Office of the Deputy Prime Minister, they included surgery opening times, appointment procedures, location, financial disincentives and discrimination.5 Reasons for discrimination include perceptions that they are migrant, violent, antisocial or ‘undeserving’.6,7 Additionally, we contend that some homeless people face a further risk of exclusion because of their age, gender, ethnic background or sexual orientation. In primary care, challenging behaviour can be an issue, but categorization of an individual as ‘deserving’ or ‘undeserving’ takes no account of the societal factors such as unemployment and poverty that can lead to homelessness.8 The General Medical Council exhorts doctors not to allow personal views about patients' race, culture, gender, sexuality or age to prejudice the care they receive.9 This places a challenge to clinicians not to exclude people from healthcare on account of homelessness or possible drug-using culture.

A comprehensive account of the management of the common health problems associated with homelessness is beyond the scope of this paper. Here we seek to describe the principles of best practice.
[27] DIFFERENTIAL CYTOKINE PATTERN OF HDV-SPECIFIC CELLULAR IMMUNE RESPONSES DISTINGUISHES TREATMENT RESPONDER AND NONRESPONDER TO PEG-IFNa-2a TREATMENT: RESULTS FROM THE HEP-NET/INTERNATIONAL HIDIT-1 STUDY
Authors: H. Wedemeyer, A. Ciner, C. Yurdaydin, K. Zachou, N. Asian, S. Meyer, B. Heidrich, M.P. Manns
Journal: Journal of Hepatology (2007)
I2 Imaging: Cancer Biology and the Tumor Microenvironment
Authors: Bonnie F. Sloane, Robert J. Gillies, Suresh Mohla, John A. Sogn, Anne E. Menkens, Daniel C. Sullivan
Journal: Cancer Research (2006)

The use of imaging techniques to understand the role of the tumor microenvironment in cancer progression was the topic of a National Cancer Institute (NCI)-sponsored think tank entitled "I2 Imaging: Cancer Biology and the Tumor Microenvironment," held in Alexandria, Virginia on June 8 to 10, 2006. Participants discussed both recent progress in the use of imaging to dissect cellular and molecular interactions within the tumor microenvironment and the challenges that remain. Recommendations made to the NCI included (a) holding an annual meeting at which biologists, clinicians, and imaging scientists could exchange data, facilitating new collaborations within this multidisciplinary field; (b) funding both research and training specifically designed to foster a cross-disciplinary focus; (c) creating and making available a variety of resources to interested investigators, such as a repository of stromal cells and extracellular matrix molecules; and (d) taking steps to encourage translation of the basic research findings into the clinic.
A Dendritic Cell Vaccine Pulsed with Autologous Hypochlorous Acid-Oxidized Ovarian Cancer Lysate Primes Effective Broad Antitumor Immunity: From Bench to Bedside
Authors: Cheryl Lai-Lai Chiang, Lana E. Kandalaft, Janos Tanyi, Andrea R. Hagemann, Gregory T. Motz, Nikolaos Svoronos, Kathleen Montone, Gina M. Mantia-Smaldone, Lori Smith, Harvey L. Nisenbaum, Bruce L. Levine, Michael Kalos, Brian J. Czerniecki, Drew A. Torigian, Daniel J. Powell, Rosemarie Mick, George Coukos
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Whole tumor lysates are promising antigen sources for dendritic cell (DC) therapy as they contain many relevant immunogenic epitopes to help prevent tumor escape. Two common methods of tumor lysate preparations are freeze-thaw processing and UVB irradiation to induce necrosis and apoptosis, respectively. Hypochlorous acid (HOCl) oxidation is a new method for inducing primary necrosis and enhancing the immunogenicity of tumor cells. Experimental Design: We compared the ability of DCs to engulf three different tumor lysate preparations, produce T-helper 1 (TH1)-priming cytokines and chemokines, stimulate mixed leukocyte reactions (MLR), and finally elicit T-cell responses capable of controlling tumor growth in vivo. Results: We showed that DCs engulfed HOCl-oxidized lysate most efficiently stimulated robust MLRs, and elicited strong tumor-specific IFN-γ secretions in autologous T cells. These DCs produced the highest levels of TH1-priming cytokines and chemokines, including interleukin (IL)-12. Mice vaccinated with HOCl-oxidized ID8-ova lysate–pulsed DCs developed T-cell responses that effectively controlled tumor growth. Safety, immunogenicity of autologous DCs pulsed with HOCl-oxidized autologous tumor lysate (OCDC vaccine), clinical efficacy, and progression-free survival (PFS) were evaluated in a pilot study of five subjects with recurrent ovarian cancer. OCDC vaccination produced few grade 1 toxicities and elicited potent T-cell responses against known ovarian tumor antigens. Circulating regulatory T cells and serum IL-10 were also reduced. Two subjects experienced durable PFS of 24 months or more after OCDC. Conclusions: This is the first study showing the potential efficacy of a DC vaccine pulsed with HOCl-oxidized tumor lysate, a novel approach in preparing DC vaccine that is potentially applicable to many cancers. Clin Cancer Res; 19(17); 4801–15. ©2013 AACR.
Altitude training and physiological conditioning from the practical point of view of the runner.
Authors: T. F. Johnston, D. M. Turner
Journal: British Journal of Sports Medicine (1974)

An individual's adaptation to altitude and the likely improvement in sea level performance resulting from it are not easily predicted from a knowledge of his sea-level performances.In Mellerowicz's study (Table I) the outstanding sea-level runner (Oh) had the largest decrement on first going to altitude but showed the greatest improvement during the four weeks at St Moritz.The slowest sea-level runner (Ec) on the other hand was least affected by altitude initially but showed the smallest improvement on return to sea level.Indeed, his sea-level time on first returning from St Moritz was slower than his time immediately before his departure to altitude.This table illustrates the astonishing individual variation both in response to altitude and in the benefit gained on return to sea level.Even at the end of four weeks the original "pecking order" has not been restored and seven of 11 individuals are still improving -and two continuing to get worse steadily.
CT to the rescue in benign, symmetrical mediastinal lipomatosis
Authors: Shivali Kashikar, Amol Jayant Gulkari, Pooja Kailash Singhania
Journal: Thorax (2012)

Images in ThoraxCT to the rescue in benign, symmetrical mediastinal lipomatosis A 34-year-old woman presented to the chest physician with progressively increasing shortness of breath.She was non-diabetic, non-hypertensive, non-obese without any other co-morbid illnesses.There was no history of prolonged drug intake of any sort.Other associated diseases like Cushing's syndrome were excluded.A chest radiograph (postero-anterior view) revealed a veil-like opacity in the mediastinum obscuring the cardiac borders (figure 1).To further evaluate the nature of mediastinal pathology, a chest CT was done.The CT showed gross, bilaterally symmetrical masses of adipose tissue in the mediastinum causing segmental atelectasis of the lungs (figure 2).The fatty tissue extended from the superior mediastinum into the anterior mediastinum up to the diaphragm.It exhibited a range of attenuation values from À155 to À110 Hounsfield units.The diagnosis of extensive mediastinal lipomatosis was established, which was proven by a biopsy from the mass.In this condition, mature adipose tissue is deposited symmetrically in the mediastinum. 1The mediastinal lipomatosis in this case is idiopathic.
Cytotoxic drugs for patients with breast cancer in the era of targeted treatment: back to the future?
Authors: J T Ribeiro, L T Macedo, G Curigliano, L Fumagalli, M Locatelli, M Dalton, A Quintela, J B C Carvalheira, S Manunta, L Mazzarella, J Brollo, A Goldhirsch
Journal: Annals of Oncology (2011)
Nonreceptor Protein-Tyrosine Phosphatases in Immune Cell Signaling
Authors: Lily I. Pao, Karen Badour, Katherine A. Siminovitch, Benjamin G. Neel
Journal: Annual Review of Immunology (2007)

Tyrosyl phosphorylation plays a critical role in multiple signaling pathways regulating innate and acquired immunity. Although tyrosyl phosphorylation is a reversible process, we know much more about the functions of protein-tyrosine kinases (PTKs) than about protein-tyrosine phosphatases (PTPs). Genome sequencing efforts have revealed a large and diverse superfamily of PTPs, which can be subdivided into receptor-like (RPTPs) and nonreceptor (NRPTPs). The role of the RPTP CD45 in immune cell signaling is well known, but those of most other PTPs remain poorly understood. Here, we review the mechanism of action, regulation, and physiological functions of NRPTPs in immune cell signaling. Such an analysis indicates that PTPs are as important as PTKs in regulating the immune system.
Major histocompatibility complex class I presentation of peptides derived from soluble exogenous antigen by a subset of cells engaged in phagocytosis.
Authors: C Reis e Sousa, R N Germain
Journal: The Journal of Experimental Medicine (1995)

Major histocompatibility complex (MHC) class I molecules generally present peptides derived from cytoplasmic proteins, but recent reports have suggested that macrophages (M phi) may be uniquely able to present exogenous antigens via these molecules, and that particle-associated antigens show a marked increase in the efficiency of such presentation. We confirm here that particle uptake by M phi permits exogenous ovaalbumin (OVA) to gain access to the endogenous class I processing pathway, an event that occurs rarely, if at all, in the absence of phagocytic stimuli. Presentation of soluble protein antigens by MHC class I molecules, however, is not limited to M phi, nor is direct coupling of antigen to the particle required. A variety of unconjugated particles promoted presentation of simultaneously offered soluble OVA to Kb-restricted T cells by both M phi and non-M phi antigen-presenting cells (APC), provided the latter could phagocytose the particles. Enhancement of presentation by phagocytic stimuli could not be explained by greater delivery of soluble antigen to endosomal compartments because such stimuli did not increase soluble tracer accumulation, nor did they improve presentation of OVA to an MHC class II-restricted T cell hybridoma. OVA presentation induced by cophagocytosis of particles and free antigen was nevertheless very inefficient in comparison to presentation of OVA peptide, and even modest responses required high concentrations of protein and particles. Furthermore, only a fraction of APC exposed to OVA and particles were lysed by anti-OVA cytotoxic T lymphocytes, despite virtually all cells showing OVA accumulation, particle uptake, and Kb expression. Titration experiments were most consistent with a model in which, by disrupting membrane integrity, phagocytic overload ("indigestion") allows escape of OVA into the cytosol of some APC, rather than with a model in which phagocytosis activates a novel antigen processing pathway that has evolved to permit class I loading of exogenous antigen. These data suggest caution in the development of vaccine strategies based on use of particle conjugates for elicitation of CD8+ T cell immunity, but, at the same time, may be relevant to understanding class I-restricted responses to some intracellular pathogens normally resident in membrane-bound vesicles.
Increased Intestinal Lipid Absorption Caused by Ire1β Deficiency Contributes to Hyperlipidemia and Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Jahangir Iqbal, Joyce Queiroz, Yan Li, Xian-Cheng Jiang, David Ron, M. Mahmood Hussain
Journal: Circulation Research (2012)

High fasting serum lipid levels are significant risk factors for atherosclerosis. However, the contributions of postprandial excursions in serum lipoproteins to atherogenesis are less well-characterized.This study aims to delineate whether changes in intestinal lipid absorption associated with loss of inositol-requiring enzyme 1β (Ire1β) would affect the development of hyperlipidemia and atherosclerosis in Apoe(-/-) mice.We used Ire1β-deficient mice to assess the contribution of intestinal lipid absorption to atherosclerosis. Here, we show that Ire1b(-/-)/Apoe(-/-) mice contain higher levels of intestinal microsomal triglyceride transfer protein, absorb more lipids, exhibit hyperlipidemia, and have higher levels of atherosclerotic plaques compared with Apoe(-/-) mice when fed chow and western diets.These studies indicate that Ire1β regulates intestinal lipid absorption and that increased intestinal lipoprotein production contributes to atherosclerosis.
A systems-biology approach to understanding the ciliopathy disorders
Authors: Ji Eun Lee, Joseph G Gleeson
Journal: Genome Medicine (2011)

'Ciliopathies' are an emerging class of genetic multisystemic human disorders that are caused by a multitude of largely unrelated genes that affect ciliary structure/function. They are unified by shared clinical features, such as mental retardation, cystic kidney, retinal defects and polydactyly, and by the common localization of the protein products of these genes at or near the primary cilium of cells. With the realization that many previously disparate conditions are a part of this spectrum of disorders, there has been tremendous interest in the function of cilia in developmental signaling and homeostasis. Ciliopathies are mostly inherited as simple recessive traits, but phenotypic expressivity is under the control of numerous genetic modifiers, putting these conditions at the interface of simple and complex genetics. In this review, we discuss the ever-expanding ciliopathy field, which has three interrelated goals: developing a comprehensive understanding of genes mutated in the ciliopathies and required for ciliogenesis; understanding how the encoded proteins work together in complexes and networks to modulate activity and structure-function relationships; and uncovering signaling pathways and modifier relationships.
Prognostic value of unrelated atypical serum immunofixation patterns during Multiple Myeloma therapy
Authors: Cristina Guimarães, Rui Bergantim, Renata Ramalho, Nuno Couto, João T Guimarães, Fernanda Trigo
Journal: Journal of Hematology & Oncology (2012)

Abstract Autologous stem cell transplantation (ASCT) is the gold standard therapy for suitable multiple myeloma (MM) patients after induction with high dose therapy. To date, the evidence of a reliable marker of prognosis in these cases remains scarce. Our aim was to evaluate appearance of unrelated atypical serum immunofixation patterns (ASIPs) as a marker of prognosis in MM patients submitted to ASCT. We retrospectively analysed data from 65 patients. Interestingly, we observed that presence of ASIPs was associated with longer progression-free survival and longer overall survival. Our results suggested that presence of ASIPs could be a novel marker of good prognosis in MM patients submitted to ASCT.
Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression
Authors: Matteo Trudu, Sylvie Janas, Chiara Lanzani, Huguette Debaix, Céline Schaeffer, Masami Ikehata, Lorena Citterio, Sylvie Demaretz, Francesco Trevisani, Giuseppe Ristagno, Bob Glaudemans, Kamel Laghmani, Giacomo Dell'Antonio, Johannes Loffing, Maria P Rastaldi, Paolo Manunta, Olivier Devuyst, Luca Rampoldi
Journal: Nature Medicine (2013)
Impact of a Molecular Approach to Improve the Microbiological Diagnosis of Infective Heart Valve Endocarditis
Authors: Claudia Breitkopf, Dieter Hammel, Hans H. Scheld, Georg Peters, Karsten Becker
Journal: Circulation (2005)

Background— Even today, infective endocarditis (IE) remains a severe and potentially fatal disease demanding sophisticated diagnostic strategies for detection of the causative microorganisms. Despite the use of appropriate laboratory techniques, classic microbiological diagnostics are characterized by a high rate of negative results. Methods and Results— Broad-range polymerase chain reaction (PCR) targeting bacterial and fungal rDNA followed by direct sequencing was applied to excised heart valves (n=52) collected from 51 patients with suspected infectious endocarditis and from 16 patients without any signs of IE during an 18-month period. The sensitivity, specificity, and the positive and negative predictive values for the bacterial broad-range PCR were 41.2%, 100.0%, 100.0%, and 34.8%, respectively, compared with 7.8%, 93.7%, 80.0%, and 24.2% for culture and 11.8%, 100.0%, 100.0%, and 26.2% for Gram staining. Without exception, database analyses allowed identification up to the (sub)species level comprising streptococcal (n=13), staphylococcal (n=4), enterococcal (n=2), and other signature sequences such as Bartonella quintana and Nocardia paucivorans. Fungal ribosomal sequences were not amplified. All valve tissues of the reference group were negative for both PCR and conventional methods, except one sample that was contaminated by molds. Conclusions— Culture-independent molecular methods substantially improve the diagnostic outcome of microbiological examination of excised heart valves. Importantly, this was true not only for fastidious, slow-growing, and/or nonculturable microorganisms but also for easy-to-culture pathogens such as streptococci and staphylococci. Both patient management and empiric antibiotic therapy of IE are likely to benefit from improved knowledge of the spectrum of pathogens now causing IE.