tbuckley/cabot-search huggingface dataset:
Vascularity and tendon pathology in the rotator cuff: a review of literature and implications for rehabilitation and surgery
Authors: E J Hegedus, C Cook, M Brennan, D Wyland, J C Garrison, D Driesner
Journal: British Journal of Sports Medicine (2009)

Objective To compile histological and imaging research detailing the microvascularity of the rotator cuff and determine the clinical application of these findings for clinicians. Methods A computer-assisted literature search of MEDLINE (1966 to September 2008) using keywords related to blood flow to the shoulder and limited to humans and English language. A hand search was also performed by three of the authors. Results Nineteen studies met inclusion and exclusion criteria. Conclusions The relationship between the variables of vascularity, age and degeneration remains unclear. Recent studies with stronger design and better technology support the fact that increased vascularity is a normal response to smaller tears, but that as tear size increases the healing response fails and decreased vascularity is observed. Also, impingement may cause hypovascularity. These studies support the possibility that people without symptoms may have normal blood flow even with ageing. Finally, exercise may increase blood flow to the rotator cuff. These findings have both surgical and rehabilitation implications.
Efficacy, Safety, Pharmacokinetics, and Biomarkers of Cediranib Monotherapy in Advanced Hepatocellular Carcinoma: A Phase II Study
Authors: Andrew X. Zhu, Marek Ancukiewicz, Jeffrey G. Supko, Dushyant V. Sahani, Lawrence S. Blaszkowsky, Jeffrey A. Meyerhardt, Thomas A. Abrams, Nadine Jackson McCleary, Pankaj Bhargava, Alona Muzikansky, Susan Sheehan, Eileen Regan, Eamala Vasudev, Michelle Knowles, Charles S. Fuchs, David P. Ryan, Rakesh K. Jain, Dan G. Duda
Journal: Clinical Cancer Research (2013)

We conducted a single-arm phase II study of cediranib, a pan-VEGFR tyrosine kinase inhibitor, in patients with advanced hepatocellular carcinoma (HCC).Patients with histologically confirmed measurable advanced HCC and adequate hematologic, hepatic, and renal functions received cediranib 30-mg orally once daily (4 weeks/cycle). The primary endpoint was progression-free survival (PFS) rate at 3 months. Other endpoints included response rates, overall survival (OS), pharmacokinetics (PK), and biomarkers for cediranib.Cediranib treatment resulted in an estimated 3-month PFS rate of 77% (60%, 99%). Median PFS was 5.3 (3.5,9.7) months, stable disease was seen in 5/17 patients (29%), and median OS was 11.7 (7.5-13.6) months. Grade 3 toxicities included hypertension (29%), hyponatremia (29%), and hyperbilirubinemia (18%). Cediranib PK were comparable to those seen in cancer patients with normal hepatic function. Plasma levels of VEGF and PlGF increased and sVEGFR1, sVEGFR2, and Ang-2 decreased after cediranib treatment. PFS was inversely correlated with baseline levels of VEGF, sVEGFR2, and bFGF and with on-treatment levels of bFGF and IGF-1, and directly associated with on-treatment levels of IFN-γ. OS was inversely correlated with baseline levels of sVEGFR1, Ang-2, TNF-α, CAIX, and CD34(+)CD133(+)CD45(dim) circulating progenitor cells and on-treatment levels of sVEGFR2.Despite the limitations of primary endpoint selection, cediranib at 30-mg daily showed a high incidence of toxicity and preliminary evidence of antitumor activity in advanced HCC. Hepatic dysfunction did not seem to affect the steady-state PK of cediranib. Exploratory studies suggested proangiogenic and inflammatory factors as potential biomarkers of anti-VEGF therapy in HCC.
Altered Immune Responses in Interleukin 10 Transgenic Mice
Authors: Amy Hagenbaugh, Sherven Sharma, Steven M. Dubinett, Sherry H.-Y. Wei, Richard Aranda, Hilde Cheroutre, Deborah J. Fowell, Scott Binder, Betty Tsao, Richard M. Locksley, Kevin W. Moore, Mitchell Kronenberg
Journal: The Journal of Experimental Medicine (1997)

Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad array of immune parameters including T helper cell type 1 (Th1) cytokine production, antigen presentation, and antigenspecific T cell proliferation. To understand the consequences of altered expression of IL-10 in immune models of autoimmune disease, the response to infectious agents, and the response to tumors, we developed transgenic mice expressing IL-10 under the control of the IL-2 promoter. Upon in vitro stimulation, spleen cells from unimmunized transgenic mice secrete higher levels of IL-10 and lower amounts of IFN-γ than do controls, although no gross abnormalities were detected in lymphocyte populations or serum Ig levels. Transfer of normally pathogenic CD4+ CD45RBhigh splenic T cells from IL-10 transgenic mice did not cause colitis in recipient severe combined immunodeficiency mice. Furthermore, co-transfer of these transgenic cells with CD4+ CD45RBhigh T cells from control mice prevented disease. Transgenic mice retained their resistance to Leishmania major infection, indicating that their cell-mediated immune responses were not globally suppressed. Lastly, in comparison to controls, IL-10 transgenic mice were unable to limit the growth of immunogenic tumors. Administration of blocking IL-10 mAbs restored in vivo antitumor responses in the transgenic mice. These results demonstrate that a single alteration in the T cell cytokine profile can lead to dramatic changes in immune responses in a manner that is stimulus dependent. These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10.
STUDIES OF SERUM CREATINE TOLERANCE. I. FINDINGS IN NORMAL MALES AND IN HYPERTHYROIDISM 12
Authors: John H. Peters, Robert Schwartz, Howard Mermelstein, Mercine N. Nefores, Matthew M. Mansuy
Journal: Journal of Clinical Investigation (1951)

In 1929, Palmer, Carson, and Sloan (1) re- ported that treatment of exophthalmic goiter with Lugol's solution reduced or abolished the associated creatinuria.More recently Richardson and Shorr (2, 3) and Thorn (4) have shown that hyperthy- roid individuals excrete a larger proportion of a given dose of creatine than do comparable normal individuals, and that this "reduced tolerance" is partially or totally reversible by effective therapy.The development by one of us of a practical method for the determination of creatine in serum (5) led Tierney and J. P. Peters to investigate the effects of exogenous creatine on serum levels in normal humans and in thyroid disease (6).Their findings revealed that the increased creatinuria reflected in- creased serum concentrations, and that the "criti- cal" serum level for the excretion of creatine was approximately 0.6 mg.%b.Because of the differences in the mode of excretion of creatine by adult males and females, we have undertaken a study of serum creatine toler- ances of men with hyperthyroidism and of others with clinical conditions simulating Graves' disease in order to further define the nature of sex differ- ences in creatine metabolism.It also seemed important to determine whether the increased tolerance noted by Tierney and Peters in one male (6) was a characteristic of this disease in men. MATERIALS AND METHODSThirteen "normal" subjects were selected from labora- tory personnel, faculty members and resident physicians
Exposure assessment of trichloroethylene.
Authors: C Wu, J Schaum
Journal: Environmental Health Perspectives (2000)

This article reviews exposure information available for trichloroethylene (TCE) and assesses the magnitude of human exposure. The primary sources releasing TCE into the environment are metal cleaning and degreasing operations. Releases occur into all media but mostly into the air due to its volatility. It is also moderately soluble in water and can leach from soils into groundwater. TCE has commonly been found in ambient air, surface water, and groundwaters. The 1998 air levels in microg/m(3) across 115 monitors can be summarized as follows: range = 0.01-3.9, mean = 0.88. A California survey of large water utilities in 1984 found a median concentration of 3.0 microg/L. General population exposure to TCE occurs primarily by inhalation and water ingestion. Typical average daily intakes have been estimated as 11-33 microg/day for inhalation and 2-20 microg/day for ingestion. A small portion of the population is expected to have elevated exposures as a result of one or more of these pathways: inhalation exposures to workers involved in degreasing operations, ingestion and inhalation exposures occurring in homes with private wells located near disposal/contamination sites, and inhalation exposures to consumers using TCE products in areas of poor ventilation. More current and more extensive data on TCE levels in indoor air, water, and soil are needed to better characterize the distribution of background exposures in the general population and elevated exposures in special subpopulations.
Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice
Authors: L.V. Sequist, R.S. Heist, A.T. Shaw, P. Fidias, R. Rosovsky, J.S. Temel, I.T. Lennes, S. Digumarthy, B.A. Waltman, E. Bast, S. Tammireddy, L. Morrissey, A. Muzikansky, S.B. Goldberg, J. Gainor, C.L. Channick, J.C. Wain, H. Gaissert, D.M. Donahue, A. Muniappan, C. Wright, H. Willers, D.J. Mathisen, N.C. Choi, J. Baselga, T.J. Lynch, L.W. Ellisen, M. Mino-Kenudson, M. Lanuti, D.R. Borger, A.J. Iafrate, J.A. Engelman, D. Dias-Santagata
Journal: Annals of Oncology (2011)
Enhanced Chemokine Receptor Recycling and Impaired S1P1 Expression Promote Leukemic Cell Infiltration of Lymph Nodes in Chronic Lymphocytic Leukemia
Authors: Laura Patrussi, Nagaja Capitani, Veronica Martini, Marco Pizzi, Valentina Trimarco, Federica Frezzato, Filippo Marino, Gianpietro Semenzato, Livio Trentin, Cosima T. Baldari
Journal: Cancer Research (2015)

Lymphocyte trafficking is orchestrated by chemokine and sphingosine 1-phosphate (S1P) receptors that enable homing and egress from secondary lymphoid organs (SLO). These receptors undergo rapid internalization and plasma membrane recycling to calibrate cellular responses to local chemoattractants. Circulating chronic lymphocytic leukemia (CLL) cells display an abnormal increase in the surface levels of the homing receptors CCR7 and CXCR4 concomitant with low S1P receptor 1 (S1P1) expression. In this study, we investigated the role of receptor recycling on CXCR4/CCR7 surface levels in CLL cells and addressed the impact of quantitative alterations of these receptors and S1P1 on the ability of leukemic cells to accumulate in SLOs. We show that recycling accounts, to a major extent, for the high levels of surface CXCR4/CCR7 on CLL cells. In addition, increased expression of these receptors, together with S1P1 deficiency, is detectable not only in circulating leukemic cells, but also in SLOs of CLL patients with lymphoadenopathy. We further provide evidence that ibrutinib, a Btk inhibitor that promotes mobilization of leukemic cells from SLOs, normalizes the imbalance between CXCR4/CCR7 and S1P1. Taken together, our results highlight the relevance of chemokine and S1P receptor recycling in CLL pathogenesis and clinical outcome.
Use of Reprogrammed Cells to Identify Therapy for Respiratory Papillomatosis
Authors: Hang Yuan, Scott Myers, Jingang Wang, Dan Zhou, Jennifer A. Woo, Bhaskar Kallakury, Andrew Ju, Michael Bazylewicz, Yvonne M. Carter, Christopher Albanese, Nazaneen Grant, Aziza Shad, Anatoly Dritschilo, Xuefeng Liu, Richard Schlegel
Journal: New England Journal of Medicine (2012)

A patient with a 20-year history of recurrent respiratory papillomatosis had progressive, bilateral tumor invasion of the lung parenchyma. We used conditional reprogramming to generate cell cultures from the patient's normal and tumorous lung tissue. Analysis revealed that the laryngeal tumor cells contained a wild-type 7.9-kb human papillomavirus virus type 11 (HPV-11) genome, whereas the pulmonary tumor cells contained a 10.4-kb genome. The increased size of the latter viral genome was due to duplication of the promoter and oncogene regions. Chemosensitivity testing identified vorinostat as a potential therapeutic agent. At 3 months after treatment initiation, tumor sizes had stabilized, with durable effects at 15 months.
Corneal Advanced Glycation End Products Increase in Patients With Proliferative Diabetic Retinopathy
Authors: Eiichi Sato, Fumihiko Mori, Sho Igarashi, Tohru Abiko, Masumi Takeda, Satoshi Ishiko, Akitoshi Yoshida
Journal: Diabetes Care (2001)

OBJECTIVE—To evaluate corneal advanced glycation end product (AGE) fluorescence in patients with diabetes and in healthy control subjects. RESEARCH DESIGN AND METHODS—Corneal autofluorescence was measured in 26 eyes of 26 patients with type 2 diabetes (mean age 57.0 years; mean disease duration 12.2 years; mean HbA1c 7.1%) and 13 eyes of 13 healthy age-matched control subjects (mean age 57.9 years). The patients with type 2 diabetes were divided into the following groups: patients without diabetic retinopathy (DR), patients without proliferative diabetic retinopathy (PDR), and patients with PDR. Corneal autofluorescence was measured by fluorophotometry with the wavelength that is characteristic of AGE fluorescence (excitation and emission 360–370 nm and 430–450 nm, respectively). We defined peak corneal autofluorescence levels as corneal AGE fluorescence values. We compared the corneal AGE fluorescence values in the four groups. RESULTS—In the PDR group (11.9 ± 3.9 arbitrary units [mean ± SD]), the corneal AGE fluorescence values were significantly higher compared with the control subjects (6.9 ± 1.3 arbitrary units), the patients without DR (7.4 ± 2.1 arbitrary units), and the patients without PDR (6.9 ± 2.2 arbitrary units) (P &amp;lt; 0.05). CONCLUSIONS—We found that corneal AGEs may increase in patients with diabetes and PDR compared with control subjects, patients without DR, and patients without PDR. In the patients with PDR, increased corneal AGEs may play a role in diabetic keratopathy.
Increased Expression of the Copper Efflux Transporter ATP7A Mediates Resistance to Cisplatin, Carboplatin, and Oxaliplatin in Ovarian Cancer Cells
Authors: Goli Samimi, Roohangiz Safaei, Kuniyuki Katano, Alison K. Holzer, Myriam Rochdi, Mika Tomioka, Murray Goodman, Stephen B. Howell
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The goal of this study was to determine the effect of small changes in ATP7A expression on the pharmacodynamics of cisplatin, carboplatin, and oxaliplatin in human ovarian carcinoma cells. Experimental Design: Drug sensitivity and cellular pharmacology parameters were determined in human 2008 ovarian carcinoma cells and a subline transfected with an ATP7A-expression vector ATP7A (2008/MNK). Drug sensitivity was determined by clonogenic assay, platinum (Pt) levels were measured by inductively coupled plasma mass spectroscopy, copper (Cu) accumulation was quantified with 64Cu, and the subcellular distribution of ATP7A was assessed by confocal digital microscopy. Results: The 1.5-fold higher expression of ATP7A in the 2008/MNK cells was sufficient to alter Cu cellular pharmacokinetics but not confer Cu resistance. In contrast, it was sufficient to render the 2008/MNK cells resistant to cisplatin, carboplatin, and oxaliplatin. Resistance was associated with increased rather than decreased whole-cell Pt drug accumulation and increased sequestration of Pt into the vesicular fraction. Cu triggered relocalization of ATP7A away from the perinuclear region, whereas at equitoxic concentrations the Pt drugs did not. Conclusions: A small increase in ATP7A expression produced resistance to all three of the clinically available Pt drugs. Whereas increased expression of ATP7A reduced Cu accumulation, it did not reduce accumulation of the Pt drugs. Under conditions where Cu triggered ATP7A relocalization, the Pt drugs did not. Thus, although ATP7A is an important determinant of sensitivity to the Pt drugs, there are substantial differences between Cu and the Pt drugs with respect to how they interact with ATP7A and the mechanism by which ATP7A protects the cell.
Studies on the release of leukotrienes and histamine by human lung parenchymal and bronchial fragments upon immunologic and nonimmunologic stimulation. Effects of nordihydroguaiaretic acid, aspirin, and sodium cromoglycate.
Authors: H Salari, P Borgeat, M Fournier, J Hebert, G Pelletier
Journal: The Journal of Experimental Medicine (1985)

Fragments of human lung parenchyma or bronchi were studied by high performance liquid chromatography, gas chromatography-mass spectrometry, and bioassay for the biosynthesis of 5-lipoxygenase metabolites of arachidonic acid, and by radioenzymatic assay for the release of histamine, upon immunologic and nonimmunologic stimulation. Human lung parenchyma were passively sensitized with serum from timothy-positive allergic patients (radioallergosorbent test, 30-40%) and challenged with 0.5 microgram/ml of timothy allergen. Analysis of the incubation media showed the presence of LTB4, LTC4, LTD4, LTE4, and histamine. Maximum release of LTB4 and LTD4 was observed after 15 min of challenge (92.8 +/- 21, and 67.8 +/- 14 pmol/g tissue wet weight, respectively; mean +/- SEM) whereas maximum release of LTC4 was observed after 5 min of challenge (25 +/- 7.1 pmol). In parallel to leukotriene formation, histamine was released rapidly and reached a maximum after approximately 15 min of challenge (2.85 +/- 0.76 nmol/g tissue). When fragments of human lung parenchyma were stimulated with ionophore A23187 (4 microM), we observed a profile of leukotriene and histamine release similar to that seen in response to the allergen. Ionophore A23187 stimulated the release of two- to fivefold greater amounts of leukotrienes and histamine than did the allergen. Release of LTC4 and histamine was maximal after 5 min of stimulation (83 +/- 22.2 and 5.2 +/- 0.95 nmol/g tissue, respectively), whereas LTB4 and LTD4 release reached a maximum after 15 min (438 +/- 66.6 and 205 +/- 68 nmol/g tissue, respectively). In addition, human lung parenchyma metabolized LTB4 into omega-OH-LTB4 and omega-COOH-LTB4. This tissue also released 5-hydroxy-eicosatetraenoic acid (5-Hete), 12-Hete, and 15-Hete. Fragments of human lung bronchi also released a similar profile of leukotrienes (except LTC4) and histamine when challenged with the allergen or ionophore A23187. Maximum release of LTB4 and LTD4 by allergen or ionophore stimulation was observed after approximately 15 min (40 +/- 7.5 and 21 +/- 8 pmol/g tissue, respectively, upon allergen challenge; 100 +/- 13 and 47 +/- 10.6 pmol/g tissue, respectively, upon ionophore stimulation). The maximum release of histamine by bronchi was observed after approximately 15 min of allergen challenge and 5 min of ionophore stimulation (2.25 +/- 0.65 and 3.15 +/- 0.9 nmol/g tissue, respectively). The release of leukotrienes but not of histamine by human lung parenchyma upon both allergen and ionophore challenge was inhibited by nordihydroguaiaretic acid (NDGA) (ID50, 2 X 10(-6)M).(ABSTRACT TRUNCATED AT 400 WORDS)
The epidemic has gone global: can Exercise is Medicine help quell the tide?
Authors: Steven D Stovitz, Mark E Batt
Journal: British Journal of Sports Medicine (2010)

The epidemic is physical inactivity and the resultant chronic diseases. Since inactivity is hard to measure, we tend to focus on its sibling, obesity. The physical inactivity epidemic seemed to start in the USA in the 1970s. And, if there's one thing the USA is not shy about, it's about sharing its supersized and sedentary culture (actually, there's not much the USA is shy about.). Now the USA, with two-thirds of its adults overweight or obese, is feeling the hollow pride of a country that set sail, got several islands in the South Pacific to jump on board, but then realised that the trip had ill-intended consequences. Like infectious epidemics, physical inactivity is spreading. Canada, New Zealand, Australia, much of South America and much of Europe have populations where over half of adults have a body mass index (BMI) above 25 (the cut-off for overweight). Globally, there are over 1 billion adults with a BMI above 25. To stress that obesity is a global problem, the WHO has coined the term, ‘globesity’. …
Gender Development and the Human Brain
Authors: Melissa Hines
Journal: Annual Review of Neuroscience (2011)

Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.
Aseptic peritonitis due to peptidoglycan contamination of pharmacopoeia standard dialysis solution
Authors: Leo Martis, Mehul Patel, Joe Giertych, Jim Mongoven, Michel Taminne, Michele A Perrier, Omar Mendoza, Niranjan Goud, Aidan Costigan, Nicole Denjoy, Christian Verger, William F Owen
Journal: The Lancet (2005)
Progression of joint damage despite control of inflammation in rheumatoid arthritis: a role for cartilage damage driven synovial fibroblast activity: Figure 1
Authors: Floris PJG Lafeber, Willemijn H Van der Laan
Journal: Annals of the Rheumatic Diseases (2012)

Past studies have shown that colonic patches, which are the gut-associated lymphoreticular tissues (GALT) in the colon, become much more pronounced in hapten-induced murine colitis, and this was associated with Th2-type T cell responses. To address the role of GALT in colonic inflammation, experimental colitis was induced in mice either lacking organized GALT or with altered GALT structures. Trinitrobenzene sulfonic acid was used to induce colitis in mice given lymphotoxin-β receptor-Ig fusion protein (LTβR-Ig) in utero, a treatment that blocked the formation of both Peyer's and colonic patches. Mice deficient in colonic patches developed focal acute ulcers with Th1-type responses, whereas lesions in normal mice were of a diffuse mucosal type with both Th1- and Th2-type cytokine production. We next determined whether LTβR-Ig could be used to treat colitis in normal or Th2-dominant, IFN-γ gene knockout (IFN-γ<sup>−/−</sup>) mice. Four weekly treatments with LTβR-Ig resulted in deletion of Peyer's and colonic patches with significant decreases in numbers of dendritic cells. This pretreatment protected IFN-γ<sup>−/−</sup> mice from trinitrobenzene sulfonic acid-induced colitis; however, in normal mice this weekly treatment was less protective. In these mice hypertrophy of colonic patches was seen after induction of colitis. We conclude that Th2-type colitis is dependent upon the presence of colonic patches. The effect of LTβR-Ig was mediated through prevention of colonic patch hypertrophy in the absence of IFN-γ. Thus, LTβR-Ig may offer a possible treatment for the Th2-dominant form of colitis.