tbuckley/cabot-search huggingface dataset:
Regulation of bone mass by Wnt signaling
Authors: V. Krishnan
Journal: Journal of Clinical Investigation (2006)

Wnt proteins are a family of secreted proteins that regulate many aspects of cell growth, differentiation, function, and death. Considerable progress has been made in our understanding of the molecular links between Wnt signaling and bone development and remodeling since initial reports that mutations in the Wnt coreceptor low-density lipoprotein receptor–related protein 5 (LRP5) are causally linked to alterations in human bone mass. Of the pathways activated by Wnts, it is signaling through the canonical (i.e., Wnt/β-catenin) pathway that increases bone mass through a number of mechanisms including renewal of stem cells, stimulation of preosteoblast replication, induction of osteoblastogenesis, and inhibition of osteoblast and osteocyte apoptosis. This pathway is an enticing target for developing drugs to battle skeletal diseases as Wnt/β-catenin signaling is composed of a series of molecular interactions that offer potential places for pharmacological intervention. In considering opportunities for anabolic drug discovery in this area, one must consider multiple factors, including (a) the roles of Wnt signaling for development, remodeling, and pathology of bone; (b) how pharmacological interventions that target this pathway may specifically treat osteoporosis and other aspects of skeletal health; and (c) whether the targets within this pathway are amenable to drug intervention. In this Review we discuss the current understanding of this pathway in terms of bone biology and assess whether targeting this pathway might yield novel therapeutics to treat typical bone disorders.
Serine enzymes released by cultured neoplastic cells.
Authors: K Danø, E Reich
Journal: The Journal of Experimental Medicine (1978)

Serine proteases or esterases released from cell cultures into the growth medium were converted to radioactive derivatives by active site labeling with tritiated DFP, both in the presence and absence of other competing active site reagents. The individual labeled enzymes were then identified by SDS-polyacrylamide gel electrophoresis and scintillation autoradiography. Conditioned medium from embryonal mouse fibroblasts transformed by mouse sarcoma virus contained five serine enzymes that were not present in medium from normal cells; two serine enzymes were released by both cell types, and one serine enzyme was found only in medium from normal cells. Two of the enzymes released by transformed cells were identified as plasminogen activators; these accounted for most of the serine enzyme labeling in transformed culture media and for most of the serine enzyme difference between normal and transformed cultures. The culture fluids from two cell strains of human neoplastic origin were examined by the same method. A rhabdomyosarcoma strain released eight serine enzymes (mol wt ranging from 22,500 to 102,000), four of which were plasminogen activators; seven serine enzymes (mol wt 26,000-102,000), including two plasminogen activators, were detected in medium from human melanoma cultures. In terms of electrophoretic mobility two of the plasminogen activators from rhabdomyosarcoma were identical with those from melanoma cultures, while the remaining two rhabdomyosarcoma activators coincided with activators found in commerical urokinase.
Tumor Necrosis Factor α Mediates Homogeneous Distribution of Liposomes in Murine Melanoma that Contributes to a Better Tumor Response
Authors: Ann L.B. Seynhaeve, Saske Hoving, Debby Schipper, Cindy E. Vermeulen, Gisela aan de Wiel-Ambagtsheer, Sandra T. van Tiel, Alexander M.M. Eggermont, Timo L.M. ten Hagen
Journal: Cancer Research (2007)

Abstract Successful treatment of solid tumors with chemotherapeutics requires that adequate levels reach the tumor cells. Tumor vascular normalization has been proposed to enhance drug delivery and improve tumor response to chemotherapy. Differently, augmenting leakage of the tumor-associated vasculature, and as such enhance vascular abnormality, may improve tumor response as well. In the present study, we show that addition of low-dose tumor necrosis factor α (TNF) to systemic injections with pegylated long circulating liposomes augmented the tumor accumulation of these liposomes 5- to 6-fold, which strongly correlated with enhanced tumor response. Using intravital microscopy, we could study the liposomal distribution inside the tumor in more detail. Especially 100 nm liposomes effectively extravasate in the surrounding tumor tissue in the presence of TNF and this occurred without any effect on tumor vascular density, branching, and diameter. Next to that, we observed in living animals that tumor cells take up the liposomes intact, followed by intracellular degradation. To our knowledge, this is an unprecedented observation. Taken together, TNF renders more tumor vessels permeable, leading to a more homogeneous distribution of the liposomes throughout the tumor, which is crucial for an optimal tumor response. We conclude that delivery of nanoparticulate drug formulations to solid tumor benefits from augmenting the vascular leakage through vascular manipulation with vasoactive drugs like TNF. [Cancer Res 2007;67(19):9455–62]
Treatment of steroid-resistant acute GVHD with OKT3 and high-dose steroids results in better disease control and lower incidence of infectious complications when compared to high-dose steroids alone: a randomized multicenter trial by the EBMT Chronic Leukemia Working Party
Authors: S Knop, H Hebart, A Gratwohl, C Kliem, C Faul, E Holler, J Apperley, H J Kolb, A Schaefer, D Niederwieser, H Einsele
Journal: Leukemia (2007)
Intra-arterial Thrombolysis of Acute Cerebral Vascular Occlusion During Endovascular Treatment of Adjacent Aneurysms at the Internal Carotid Artery
Authors: Zhi Chen, Hongping Miao, Gang Zhu, Hua Feng
Journal: JAMA Neurology (2012)

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Lobar pneumonia in Northern Zambia: clinical study of 502 adult patients.
Authors: S C Allen
Journal: Thorax (1984)

From July 1981 to January 1983 502 adults were treated for lobar or segmental pneumonia in a general hospital in Northern Zambia. Consolidation was present in either the right or the left lower lobe in 78.8%, the right middle lobe in 10.2% and either the right or the left upper lobe in 10.7%. Penicillin treatment failed to give an improvement in 10.7%, many of whom recovered after receiving either gentamicin or kanamycin. A high risk of death was associated with an age of 65 years or over, absence of pyrexia, absence of a leucocyte response, disease affecting multiple lobes, irreversible hypotension, underlying neoplasm, and failure to respond to penicillin treatment (p less than 0.001 in all cases). Penicillin remains the initial treatment of choice for lobar pneumonia in rural central Africa. Mortality can probably be reduced by inpatient treatment of as many patients with pneumonia as local circumstances allow, and by adding broad spectrum treatment in patients who show no improvement after 48 hours of penicillin treatment.
Lessons Learned from Public Health Mass Media Campaigns: Marketing Health in a Crowded Media World
Authors: Whitney Randolph, K. Viswanath
Journal: Annual Review of Public Health (2004)

Every year, new public health mass media campaigns are launched attempting to change health behavior and improve health outcomes. These campaigns enter a crowded media environment filled with messages from competing sources. Public health practitioners have to capture not only the attention of the public amid such competition, but also motivate them to change health behaviors that are often entrenched or to initiate habits that may be new or difficult. In what ways are public health mass media campaigns now attempting to succeed in a world crowded with media messages from a myriad of sources? What are the conditions that are necessary for a media campaign to successfully alter health behaviors and alter outcomes in the long term? To what extent can the successes and failures of previous campaigns be useful in teaching important lessons to those planning campaigns in the future? In this chapter we attempt to answer these questions, drawing from recent literature on public health mass media campaigns.
A simple and reproducible prognostic index in luminal ER-positive breast cancers
Authors: I. Castellano, L. Chiusa, A.M. Vandone, S. Beatrice, M. Goia, M. Donadio, R. Arisio, F. Muscarà, A. Durando, G. Viale, P. Cassoni, A. Sapino
Journal: Annals of Oncology (2013)

The group of estrogen receptor (ER)-positive breast cancers (both luminal-A and -B) behaves differently from the ER-negative group. At least in early follow-up, ER expression influences positively patients' prognosis. This low aggressive biology flattens out the differences of clinical management. Thus we aimed to produce a prognostic index specific for ER-positive (ERPI) cancers that could be of aid for clinical decision.The test set comprised 495 consecutive ER-positive breast cancers. Tumor size, number of metastatic lymph nodes and androgen receptor expression were the only independent variables related to disease-specific survival. These variables were used to create the ERPI, which was applied to the entire test set and to selected subpopulations (grade 2 (G2)-tumors, luminal-A and -B breast cancers). A series of 581 ER-positive breast cancers, collected from another hospital, was used to validate ERPI.In the test population, 96.9% of patients classified as ERPI-good showed a good prognosis compared with 79.6% classified as ERPI-poor (P < 0.001). ERPI effectively discriminated outcome in luminal-A and luminal-B and in G2-tumors. In the validation series, the ERPI maintained its value.ERPI is a practical tool in refining the prediction of outcome of patients with ER-positive breast cancer.
The autoepitope of the 74-kD mitochondrial autoantigen of primary biliary cirrhosis corresponds to the functional site of dihydrolipoamide acetyltransferase.
Authors: J Van de Water, M E Gershwin, P Leung, A Ansari, R L Coppel
Journal: The Journal of Experimental Medicine (1988)

Autoantibodies to mitochondrial antigens are characteristic of the autoimmune liver disease primary biliary cirrhosis (PBC), but the precise antigenic determinants recognized by these antibodies have not been defined. Recently, our laboratory identified a 1,370-bp rat liver cDNA clone that coded for a polypeptide recognized specifically by sera from patients with PBC but not by sera from patients with other forms of liver disease. This recombinant protein was identified as the 74-kD M2 mitochondrial inner membrane autoantigen, now known to be dihydrolipoamide acetyltransferase. In the present study, we have identified a 603-bp fragment that codes for a polypeptide containing all of the autoreactivity of the original clone. In addition, based on hydrophobicity/hydrophilicity plots of the amino acid sequence of this polypeptide segment, several peptides were synthesized and tested for reactivity by an inhibition assay using sera from patients with PBC. One peptide, defined by the amino acids AEIETDKATIGFEVQEEGYL, absorbed serum reactivity to the protein product of the original clone. Of particular interest was the finding that this peptide contains the lipoic acid binding site KATIGF of the dihydrolipoamide acetyltransferase found in the inner mitochondrial membrane. Thus, it appears that for this autoantigen, the target of the autoantibodies corresponds to a functional site of the dihydrolipoamide acetyltransferase.
Separation of helper T cells from suppressor T cells expressing different Ly components. I. Polyclonal activation: suppressor and helper activities are inherent properties of distinct T-cell subclasses.
Authors: J Jandinski, H Cantor, T Tadakuma, D L Peavy, C W Pierce
Journal: The Journal of Experimental Medicine (1976)

Concanavalin A, a nonspecific polyclonal activator of T lymphocytes, activates Lyl and Ly23 subclasses to the same degree. After activation, the Ly23 subclass, but not the Lyl subclass, has the following properties: (a) Suppression of the antibody response to sheep erythrocytes (SRBC) in vitro. (b) Production of a soluble factor that suppresses the anti-SRBC response in vitro. (c) Suppression of the generation of cell-mediated cytotoxicity to H-2 target cells in vitro. Con A-activated cells of the Lyl subclass, but not the Ly23 subclass, express helper function in the anti-SRBC response in vitro. Because the intact Con A-stimulated T-cell population contains both cell types, these cells do not exert detectable helper effects in an anti-SRBC system in vitro, because the helper effect of Lyl cells is masked by the suppressor effect of the Ly23 cells. Each function is revealed by eliminating one or the other population with the relevant Ly antiserum. The resting T-cell population, before activation by Con A, also contains already programmed Lyl and Ly23 cells with similar helper and suppressor potentials, respectively. This is revealed by experiments with Ly subclasses which have been separated from the resting T-cell population and then stimulated by Con A. Thus helper and suppressor functions, as expressed in these systems, are manifestations of separate T-cell-differentiative pathways and do not depend upon stimulation of the cells by antigen.
Fatigue in Breast Cancer Survivors: Occurrence, Correlates, and Impact on Quality of Life
Authors: Julienne E. Bower, Patricia A. Ganz, Katherine A. Desmond, Julia H. Rowland, Beth E. Meyerowitz, Thomas R. Belin
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To describe the occurrence of fatigue in a large sample of breast cancer survivors relative to general population norms and to identify demographic, medical, and psychosocial characteristics of fatigued survivors. PATIENTS AND METHODS: Breast cancer survivors in two large metropolitan areas completed standardized questionnaires as part of a survey study, including the RAND 36-item Health Survey, Center for Epidemiological Studies–Depression Scale, Breast Cancer Prevention Trial Symptom Checklist, Medical Outcomes Study Sleep Scale, and demographic and treatment-related measures. RESULTS: On average, the level of fatigue reported by the breast cancer survivors surveyed (N = 1,957) was comparable to that of age-matched women in the general population, although the breast cancer survivors were somewhat more fatigued than a more demographically similar reference group. Approximately one third of the breast cancer survivors assessed reported more severe fatigue, which was associated with significantly higher levels of depression, pain, and sleep disturbance. In addition, fatigued women were more bothered by menopausal symptoms and were somewhat more likely to have received chemotherapy (with or without radiation therapy) than nonfatigued women. In multivariate analyses, depression and pain emerged as the strongest predictors of fatigue. CONCLUSION: Although the majority of breast cancer survivors in this large and diverse sample did not experience heightened levels of fatigue relative to women in the general population, there was a subgroup of survivors who did report more severe and persistent fatigue. We identified characteristics of these women that may be helpful in elucidating the mechanisms underlying fatigue in this population, as well as directing intervention efforts.
Mind your language
Authors: A. Wall
Journal: Journal of the Royal Society of Medicine (2003)

In a recent speech the Secretary of State said that primary care is the 'frontline of the NHS'. In time of war (as it then was) that may not have been quite the metaphor he should have used. No matter, only a paragraph later he had switched to show-business with primary care becoming 'centre stage'. Later it was a 'jewel in the crown' while being 'in the driving seat'.

Language is the agent of thought. While we can indicate quite a lot without words, ultimately we depend on words and the ideas they convey to do business with each other. Figurative language, especially similes and metaphors, is intended to enhance that communication. But are we sufficiently sensitive to its impact? Do those various depictions of primary care help or hinder our understanding? Are they persuasive or manipulative? A look at some of the frequently used cliches and images may help us to see what is going on.
Reliability of Multicenter Pediatric Echocardiographic Measurements of Left Ventricular Structure and Function
Authors: Steven E. Lipshultz, Kirk A. Easley, E. John Orav, Samuel Kaplan, Thomas J. Starc, J. Timothy Bricker, Wyman W. Lai, Douglas S. Moodie, George Sopko, Mark D. Schluchter, Steven D. Colan
Journal: Circulation (2001)

Background To assess the reliability of pediatric echocardiographic measurements, we compared local measurements with those made at a central facility. Methods and Results The comparison was based on the first echocardiographic recording obtained on 735 children of HIV-infected mothers at 10 clinical sites focusing on measurements of left ventricular (LV) dimension, wall thicknesses, and fractional shortening. The recordings were measured locally and then remeasured at a central facility. The highest agreement expressed as an intraclass correlation coefficient (ICC=0.97) was noted for LV dimension, with much lower agreement for posterior wall thickness (ICC=0.65), fractional shortening (ICC=0.64), and septal wall thickness (ICC=0.50). The mean dimension was 0.03 cm smaller in central measurements (95% prediction interval [PI], −0.32 to 0.25 cm) for which 95% PI reflects the magnitude of differences between local and central measurements. Mean posterior wall thickness was 0.02 cm larger in central measurements (95% PI, −0.18 to 0.22 cm). Mean fractional shortening was 1% smaller in central measurements. However, the 95% PI was −10% to 8%, indicating that a fractional shortening of 32% measured centrally could be anywhere between 22% and 40% when measured locally. Central measurements of mean septal thickness were ≈0.1 cm thicker than local ones (95% PI, −0.18 to 0.34 cm). Centrally measured wall thickness was more closely related to mortality and possibly was more valid than local measurements. Conclusions Although LV dimension was reliably measured, local measurements of LV wall thickness and fractional shortening differed from central measurements.
Groin injuries in athletes.
Authors: P. Renström, L. Peterson
Journal: British Journal of Sports Medicine (1980)

Groin injuries in athletes are being recognised more often in sport, especially in football.In Gothenberg, a study of football injuries, both acute and chronic, revealed that 5% of all injuries were localised in the groin region.Seventeen different teams were studied.Groin pain may be caused by injuries occurring in sports such as soccer, handball, ice hockey, skating, ski-ing, hurdles, high jump, fencing, bowling, horse-riding, etc., due to overloading of the muscles producing microscopic lesions in the muscles, peri6steum, or tendons, and leading to inflammatory reaction.Symptoms may also be caused by complete or incomplete macroscopic lesions, such as disruptions in the groin muscles.Symptoms may be diffuse and uncharacteristic, and it is necessary to establish a broad differential diagnostic background.The most common injuries involve the adductor longus, rectus abdominis, iliopsoas and rectus femoris muscles. Tenoperiostitis and Strain of the Adductor LongusLoading of the adductor muscles during intensive training may lead to injury and inflammation in the region of the adductor origins, especially of the adductor longus.Symptoms often begin insiduously; pain is localised in the origin of the muscle and radiates along the medial aspect of the thigh and also towards the rectus abdominis.The pain and associated stiffness may decrease after some physical exercise and may at times disappear completely.However, the pain usually reappears with greater intensity after continued activity.If the athlete does not rest there is a risk of the so-called "pain cycle" leading to continuous pain.A chronic condition including this pain cycle may be difficult to
Intratumoral Administration of Recombinant Human Interleukin 12 in Head and Neck Squamous Cell Carcinoma Patients Elicits a T-Helper 1 Profile in the Locoregional Lymph Nodes
Authors: Carla M. van Herpen, Maaike Looman, Marijke Zonneveld, Nicole Scharenborg, Peter C. de Wilde, Louis van de Locht, Matthias A. W. Merkx, Gosse J. Adema, Pieter H. De Mulder
Journal: Clinical Cancer Research (2004)

The objective of this Phase II study was to evaluate the pharmacodynamic and immune effects of intratumorally administered recombinant human interleukin-12 (IL-12) on regional lymph nodes, primary tumor, and peripheral blood. Ten previously untreated patients with head and neck squamous cell carcinoma were injected in the primary tumor two to three times, once/week, at two dose levels of 100 or 300 ng/kg, before surgery. We compared these patients with 20 control (non-IL-12-treated) patients. Toxicity was high, with unexpected dose-limiting toxicities at the 300 ng/kg dose level. Dose-dependent plasma IFN-gamma and IL-10 increments were detected. These cytokine levels were higher after the first injection than after the subsequent injections. A rapid, transient reduction in lymphocytes, monocytes, and all lymphocyte subsets, especially natural killer cells, was observed, due to a redistribution to the lymph nodes. In the enlarged lymph nodes of the IL-12-treated patients, a higher percentage of natural killer cells and a lower percentage of T-helper cells were found compared with control patients. The same pattern was detected in the infiltrate in the primary tumor. Real-time semiquantitative PCR analysis of peripheral blood mononuclear cells in the peripheral blood showed a transient decrease of T-bet mRNA. Interestingly, the peripheral blood mononuclear cells in the lymph nodes showed a 128-fold (mean) increase of IFN-gamma mRNA. A switch from the Th2 to a Th1 profile in the lymph nodes compared with the peripheral blood occurred in the IL-12-treated patients. In conclusion, in previously untreated head and neck squamous cell carcinoma patients, recombinant human IL-12 intratumorally showed dose-limiting toxicities at the dose level of 300 ng/kg and resulted in measurable immunological responses locoregionally at both dose levels.