tbuckley/cabot-search huggingface dataset:
Cyclooxygenase-1 Deletion Enhances Apoptosis but Does Not Protect Against Ultraviolet Light-Induced Tumors
Authors: Alice P. Pentland, Glynis Scott, JoAnne VanBuskirk, Carol Tanck, Gina LaRossa, Sabine Brouxhon
Journal: Cancer Research (2004)

Abstract Inhibition or deletion of cyclooxygenase (COX)-2 has been demonstrated to protect against squamous cell cancer in many studies. Although much effort has focused on COX-2 inhibition, recent work indicates that COX-1 deletion may be nearly as protective. In this study, we used SKH-1 hairless mice in which COX-1 was selectively deleted to examine the role of COX-1 in photocarcinogenesis. After UV exposure, 40–60% less prostaglandin E2 was detected in COX-1−/− animals compared with wild-type (WT) controls. A 4-fold induction of keratinocyte apoptosis was observed in knockouts relative to WT animals, as documented by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling and caspase-3 staining. Proliferation was not significantly different in COX-1+/+, COX-1+/−, and COX-1−/− animals. When susceptibility to UV-induced tumor formation was studied, tumor number, average tumor size, and time of tumor onset in COX-1−/− animals were identical to WT controls. Thus, enhanced apoptosis did not alter UV-induced skin carcinogenesis, suggesting other effects are key to nonsteroidal anti-inflammatory drug chemoprevention. These results contrast sharply with data obtained using the classic 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate cancer model in which a prominent protective effect of COX-1−/− is present. The lack of protection observed here confirms cancer mechanisms are distinct in UV- and tumor promotor-induced cancer models and indicates that chemoprevention strategies must specifically address cancer causes to be effective.
Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck
Authors: R. Hitt, A. Irigoyen, H. Cortes-Funes, J.J. Grau, J.A. García-Sáenz, J.J. Cruz-Hernandez
Journal: Annals of Oncology (2011)
Serotonergic Neurons Mediate Dyskinesia Side Effects in Parkinson’s Patients with Neural Transplants
Authors: Marios Politis, Kit Wu, Clare Loane, Niall P. Quinn, David J. Brooks, Stig Rehncrona, Anders Bjorklund, Olle Lindvall, Paola Piccini
Journal: Science Translational Medicine (2010)

Two patients with Parkinson’s disease, successfully treated with fetal tissue transplants more than a decade ago, developed troublesome involuntary movements, which could be treated with a serotonin receptor agonist.
Bacterial translocation (BT) in cirrhosis
Authors: Reiner Wiest, Guadalupe Garcia‐Tsao
Journal: Hepatology (2005)

Gut flora and bacterial translocation (BT) play an important role in the pathogenesis of the complications of cirrhosis. Research on the pathogenesis of BT and its clinical significance transcends established boundaries between microbiology, cell biology, intestinal pathophysiology, and immunology. This review delineates multiple mechanisms involved in the process of BT, with an emphasis on alterations in intestinal flora and mucosal barrier function, particularly immunological defense mechanisms. Current knowledge on the innate and adaptive immune response that allows a "friendly" communication between bacteria and host is summarized, and alterations occurring in cirrhosis that may facilitate BT are discussed. In addition, definition of a "pathological" BT is proposed together with an analysis of the anatomical site and route of BT. Finally, therapeutic approaches for the prevention of BT in experimental and human cirrhosis are reviewed. Future research in the field of BT in cirrhosis will allow the development of new therapeutic targets in the prevention of infections and other complications of cirrhosis. (HEPATOLOGY 2005;41:422–433.)
Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1.
Authors: J A Roake, A S Rao, P J Morris, C P Larsen, D F Hankins, J M Austyn
Journal: The Journal of Experimental Medicine (1995)

Dendritic cells (DC) in nonlymphoid organs can internalize and process foreign antigens before migrating to secondary lymphoid tissues to initiate primary immune responses. However, there is little information on which stimuli promote migration of DC from the tissues. Systemic administration of lipopolysaccharide (LPS), which induces in vivo production of cytokines, led to a reduction in the numbers of major histocompatibility complex class II-positive (Ia+) leukocytes in mouse hearts and kidneys: &amp;gt; 95% of DC were depleted 1-3 d after injection of 50 micrograms LPS. Several lines of evidence indicated that this response was due to migration of DC rather than loss of Ia expression or cytotoxic effects. In skin of treated mice, the number of Ia+ epidermal Langerhans' cells (LC) was reduced, and "cords" of Ia+ leukocytes became evident in the dermis. The latter cells expressed little NLDC145 and may have originated from recruited or resident DC progenitors. Systemic administration of recombinant tumor necrosis factor (rhTNF)-alpha resulted in a decrease in numbers of Ia+ cells in heart and kidney and of epidermal LC, and it also induced dermal cords. Administration of a rh-interleukin (IL)-1 resulted in a decrease in Ia+ cells only in renal medulla, appeared to activate a subset of epidermal LC, and induced dermal cords. Similar microgram doses of rhIL-2 had no obvious effect. Treatment with a neutralizing anti-TNF antiserum before LPS administration inhibited the depletion of LC from skin but not from heart or kidney. Therefore, TNF-alpha and IL-1 alpha may promote DC migration from nonlymphoid tissues and may have differential effects on different DC populations, but it is unclear whether they act on DC directly or indirectly (e.g., via other cytokines).
A Rapid, Physiologic Protocol for Testing Transcriptional Effects of Thyroid-Disrupting Agents in Premetamorphic <i>Xenopus</i> Tadpoles
Authors: Nathalie Turque, Karima Palmier, Sébastien Le Mével, Caroline Alliot, Barbara A. Demeneix
Journal: Environmental Health Perspectives (2005)

Increasing numbers of substances present in the environment are postulated to have endocrine-disrupting effects on vertebrate populations. However, data on disruption of thyroid signaling are fragmentary, particularly at the molecular level. Thyroid hormone (TH; triiodothyronine, T3) acts principally by modulating transcription from target genes; thus, thyroid signaling is particularly amenable to analysis with a transcriptional assay. Also, T3 orchestrates amphibian metamorphosis, thereby providing an exceptional model for identifying thyroid-disrupting chemicals. We combined these two advantages to develop a method for following and quantifying the transcriptional action of T3 in Xenopus laevis tadpoles. This technology provides a means of assessing thyroid activity at the molecular level in a physiologically relevant situation. Moreover, translucent tadpoles are amenable to "on-line" imaging with fluorescent reporter constructs that facilitate in vivo measurement of transcriptional activity. We adapted transgenesis with TH-responsive elements coupled to either luciferase or green fluorescent protein to follow T3-dependent transcription in vivo. To reduce time of exposure and to synchronize responses, we optimized a physiologic pretreatment protocol that induced competence to respond to T3 and thus to assess T3 effects and T3 disruption within 48 hr. This pretreatment protocol was based on a short (24 hr), weak (10(-12) M) pulse of T3 that induced TH receptors, facilitating and synchronizing the transcriptional responses. This protocol was successfully applied to somatic and germinal transgenesis with both reporter systems. Finally, we show that the transcriptional assay allows detection of the thyroid-disrupting activity of environmentally relevant concentrations (10(-8) M) of acetochlor, a persistent herbicide.
Microtubule-Associated Histone Deacetylase 6 Supports the Calcium Store Sensor STIM1 in Mediating Malignant Cell Behaviors
Authors: Ying-Ting Chen, Yih-Fung Chen, Wen-Tai Chiu, Kuan-Yu Liu, Yu-Lin Liu, Jang-Yang Chang, Hsien-Chang Chang, Meng-Ru Shen
Journal: Cancer Research (2013)

Abstract Stromal-interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca2+ storage sensor that promotes cell growth, migration, and angiogenesis in breast and cervical cancers. Here, we report that the microtubule-associated histone deacetylase 6 (HDAC6) differentially regulates activation of STIM1-mediated store-operated Ca2+ entry (SOCE) between cervical cancer cells and normal cervical epithelial cells. Confocal microscopy of living cells indicated that microtubule integrity was necessary for STIM1 trafficking to the plasma membrane and interaction with Orai1, an essential pore subunit of SOCE. Cancer cells overexpressed both STIM1 and Orai1 compared with normal cervical epithelial cells. HDAC6 upregulation in cancer cells was accompanied by hypoacetylated α-tubulin. Tubastatin-A, a specific HDAC6 inhibitor, inhibited STIM1 translocation to plasma membrane and blocked SOCE activation in cancer cells but not normal epithelial cells. Genetic or pharmacologic inhibition of HDAC6 blocked STIM1 membrane trafficking and downstream Ca2+ influx, as evidenced by total internal reflection fluorescent images and intracellular Ca2+ determination. In contrast, HDAC6 inhibition did not affect interactions between STIM1 and the microtubule plus end-binding protein EB1. Analysis of surgical specimens confirmed that most cervical cancer tissues overexpressed STIM1 and Orai1, accompanied by hypoacetylated α-tubulin. Together, our results identify HDAC6 as a candidate target to disrupt STIM1-mediated SOCE as a general strategy to block malignant cell behavior. Cancer Res; 73(14); 4500–9. ©2013 AACR.
Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial
Authors: U Jehn, S Suciu, X Thomas, F Lefrère, P Muus, Z Berneman, J-P Marie, F Adamo, G Fillet, F Nobile, F Ricciuti, G Leone, V Rizzoli, M Montanaro, F Beeldens, P Fazi, F Mandelli, R Willemze, T de Witte, S Amadori
Journal: Leukemia (2006)
Information and communications technology in mental health care
Authors: P. McLaren
Journal: Journal of the Royal Society of Medicine (2005)

I wonder, dear reader in 2055, how much your work will depend on information and communications technology (ICT). Even today in general adult psychiatry—a specialty not traditionally associated with technology—ICT is having increasing impact on my life. In a working day, I communicate with other professionals and patients via landline telephone, mobile telephone, SMS messaging, e-mail via my office personal computer and my laptop, paper notes and videoconferencing (through the videoconferencing arises from my interest in telepsychiatry and is not much used by other psychiatrists).

Warnings have been sounded of the dangers of information overload. One local authority in the north of England recently banned its employees from e-mailing on a Thursday, to reduce unnecessary communication and stimulate thinking as to why and when an e-mail is sent. In healthcare, ICT is still underused, although large providers have become alert to the harm caused by misuse. Some organizations have curtailed use of the ‘send to all’ function on e-mail systems to cut the amount of redundant mail.

The drivers for many ICT applications have been political rather than evidence-based. As I write, the National Health Service is on the verge of delivering the largest ICT project ever undertaken—a nationwide electronic patient record. This incorporates an electronic booking system (again politically driven) that will enable general practitioners to book outpatient appointments for secondary services. The South London and Maudsley NHS Trust has implemented a clinical information management system, known as CCS, which has substantially improved the handling and quality of clinical information. All patient contacts and correspondence from nursing, medical, and social care professionals and even the local accident and emergency liaison service are recorded digitally. The duplicate paper records are becoming increasingly redundant. That CCS was fully embedded became obvious when the system crashed and a community mental health team protested loudly. The NHS is addressing the issue of data control and patients in the Trust are now asked, at inception, who should be allowed access to their personal data. The major weakness of CCS is that it is not, and will not be, linked to the local NHS general practices. The platform on which it is built is not suitable for operating with larger numbers and cannot be rolled out. This system will be subsumed by the new NHS-wide electronic patient record.
Pretreatment, Psychological, and Behavioral Predictors of Weight Outcomes Among Lifestyle Intervention Participants in the Diabetes Prevention Program (DPP)
Authors: Linda M. Delahanty, Mark Peyrot, Peter J. Shrader, Donald A. Williamson, James B. Meigs, David M. Nathan
Journal: Diabetes Care (2012)

OBJECTIVE To identify the most important pretreatment characteristics and changes in psychological and behavioral factors that predict weight outcomes in the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS Approximately 25% of DPP lifestyle intervention participants (n = 274) completed questionnaires to assess weight history and psychological and behavioral factors at baseline and 6 months after completion of the 16-session core curriculum. The change in variables from baseline to 6 months was assessed with t tests. Multivariate models using hierarchical logistic regression assessed the association of weight outcomes at end of study with each demographic, weight loss history, psychological, and behavioral factor. RESULTS At end of study, 40.5% had achieved the DPP 7% weight loss goal. Several baseline measures (older age, race, older age when first overweight, fewer self-implemented weight loss attempts, greater exercise self-efficacy, greater dietary restraint, fewer fat-related dietary behaviors, more sedentary activity level) were independent predictors of successful end-of-study weight loss with the DPP lifestyle program. The DPP core curriculum resulted in significant improvements in many psychological and behavioral targets. Changes in low-fat diet self-efficacy and dietary restraint skills predicted better long-term weight loss, and the association of low-fat diet self-efficacy with weight outcomes was explained by dietary behaviors. CONCLUSIONS Health care providers who translate the DPP lifestyle intervention should be aware of pretreatment characteristics that may hamper or enhance weight loss, consider prioritizing strategies to improve low-fat diet self-efficacy and dietary restraint skills, and examine whether taking these actions improves weight loss outcomes.
Intermediate filaments in the retina and retinoblastoma.
Authors: T Kivela, A Tarkkanen, I Virtanen
Journal: BMJ (1985)

1600, and 2400.Student's t test was used to compare growth hormone concentrations before and during treatment.The table shows mean circulating concentrations of growth hormone before and on the third day of treatment.Concentrations ranged from 32-5 to 234 mIU/l before treatment but were suppressed by 30-79% by the third day of treatment (p<0-001).The maximal reduction in growth hormone concentration was achieved two to four hours after administration of the drug and was 50-95% of the basal concentration.After administration of the drug the concentration fell within 30 minutes to 30-83% of the basal concentration in all patients and remained suppressed for up to eight hours.The patient with an intractable headache experienced relief for periods of two to three hours during the three days of treatment, which reduced his growth hormone concentration by 46%.Placebo was substituted on the fourth day and his headache promptly returned.He was then prescribed long term treatment with selective mini somatostatin in doses up to 100 Hg every three hours.After seven months' continuous treatment his symptomatic relief was maintained and his growth hormone concentration was 34% of the concentration before treatment.A further patient (case 4) was treated for five months with selective mini somatostatin 100 ug twice daily.His condition improved, and his mean growth hormone concentration remained suppressed by 80%.Neither patient 'showed glucose intolerance during treatment or reported any difficulty with self injection or side effects even with the higher dose.
FOOD PROTEIN EFFECT ON PLASMA SPECIFIC GRAVITY, PLASMA PROTEIN, AND HEMATOCRIT VALUE
Authors: T. Addis, Horace Gray, Evalyn Barrett
Journal: The Journal of Experimental Medicine (1948)

When the protein consumption of normal human individuals is increased from 0.5, to 1.5, to 2.5 gm. of protein per kilo body weight, the specific gravity of the plasma rises and the hematocrit value falls. The analysis of variance demonstrates that the change in protein consumption is a significant but minor factor in determining the total variability of the observations. When albino rats were given diets containing a small, a moderate, and a large amount of protein, there was an increase in serum protein concentration but no change in hematocrit value. During the period over which the most rapid changes in rate of urea excretion and serum urea concentration occurred as normal human individuals passed from a 2.5 to an 0.1 gm. of protein per kilo body weight consumption, there was no change in serum protein concentration. Over a 5 day period during which a diet that was adequate in calories but almost wholly devoid of protein was taken, the serum protein concentration of normal individuals steadily rose. This was associated with a slight increase in hematocrit value but no change in blood or plasma volume. The protein effect is one of the minor factors that contribute to the variability of serum protein and hematocrit measurements in normal individuals. The general conclusion is reached that we shall have to measure the rate at which red cells and protein enter and leave the circulating blood stream before we can hope to comprehend the mechanism of the protein effect.
Cell-mediated lympholysis to H-2-matched target cells modified with a series of nitrophenyl compounds.
Authors: T G Rehn, J K Inman, G M Shearer
Journal: The Journal of Experimental Medicine (1976)

The specificity of C57BL/10 cytotoxic effector cells generated by in vitro sensitization with autologous spleen cells modified with a series of related nitrophenyl compounds was investigated. The failure of trinitrophenyl (TNP)-sensitized effector cells to lyse TNP-beta-alanylglycylglycyl(AGG)-modified target cells is presented as evidence contradicting the intimacy or dual receptor model or T-cell recognition in its simplest form. Data are also shown indicating that sensitization with N-(3-nitro-4-hydroxy-5-iodophenylacetyl)-AGG-modified stimulating cells generates noncross-reacting clones of cytotoxic effector cells.
Obesity and the skin
Authors: A.R. Shipman, G.W.M. Millington
Journal: British Journal of Dermatology (2011)

Obesity is a serious global health problem, perhaps the biggest public health issue of our times. Excess body weight may be a factor in carcinogenesis in general, as well as contributing to the pathogenesis of metabolic, cardiovascular and musculoskeletal disorders. Obesity also has many cutaneous features, which form the basis for this review article. Many of these clinical entities are common to the majority of obese patients, e.g. striae distensae, plantar hyperkeratosis and an increased risk of skin infections. However, it may also be associated with poor wound healing, malignant melanoma and an increased risk of inflammatory dermatoses, such as psoriasis, as well as some rarer disorders. Therapeutic interventions for obesity, whether over-the-counter, prescription medicines or surgical interventions, are increasingly commonplace. All of these treatment modalities potentially have dermatological side-effects too.
Characterization of Punctate Inner Choroidopathy Using Enhanced Depth Imaging Optical Coherence Tomography
Authors: Javier Zarranz-Ventura, Dawn A. Sim, Pearse A. Keane, Praveen J. Patel, Mark C. Westcott, Richard W. Lee, Adnan Tufail, Carlos E. Pavesio
Journal: Ophthalmology (2014)
Treatment of lymphangioleiomyomatosis: building evidence in orphan diseases
Authors: Vincent Cottin
Journal: European Respiratory Journal (2014)

In orphan disease, a negative trial contributes to building evidence and excluding ineffective therapy from practice http://ow.ly/tvANkLymphangioleiomyomatosis (LAM) is a rare (orphan) lung disease, in which the lung parenchyma is progressively replaced by cysts associated with a proliferation of immature smooth muscle cells and perivascular epithelioid cells (so-called LAM cells) around lymphatic vessels [1,2].LAM can be sporadic, almost exclusively affecting females, or can be associated with tuberous sclerosis complex (TSC) where it affects 30-50% of adult females, and less frequently males [3][4][5][6].
STUDIES ON LYSOSOMES
Authors: Gerald Weissmann, Lewis Thomas
Journal: The Journal of Experimental Medicine (1962)

Granular fractions sedimenting between 800 g and 15,000 g have been prepared in 0.25 M sucrose from the livers of normal young rabbits and from the livers of rabbits injected with A. aerogenes endotoxin. As early as 5 minutes after endotoxin, there was an augmented release of two enzymes, beta glucuronidase and cathepsin, into the supernatant of fractions which had been incubated or incubated and irradiated with a mercury vapor lamp at 37°C. These effects were maximum at 30 minutes after endotoxin and were associated with a depletion of the total activities of the two enzymes within the granules. Concurrently there was a rise in the activity of the two enzymes in fractions of the homogenate which were unsedimentable at 15,000 g. Fractions prepared from animals made tolerant to endotoxin no longer responded to incubation and irradiation by an augmented release of these two hydrolases, nor did fractions prepared from animals pretreated with glucocorticoids. Pretreatment with DOCA did not prevent release of enzymes after endotoxin. The results have been interpreted to indicate that one consequence of the injection of endotoxin is an effect upon the stability of lysosomes, with subsequent release of acid hydrolases into the cell sap or surrounding tissue. Glucocorticoids may exert their pharmacologic effects through the protection of these subcellular particles against a variety of injurious agents.