tbuckley/cabot-search huggingface dataset:
Abstract A10: Prognostic significance of CXCL10/CXCR3 overexpression in mucinous bronchioloalveolar carcinoma
Authors: Michael Duruisseaux, Martine Antoine, Nathalie Rabbe, Virginie Poulot, Etienne Giroux Leprieur, Armelle Lavolé, Jacques Cadranel, Marie Wislez
Journal: Clinical Cancer Research (2012)

Abstract Introduction: The 2004 WHO Pathological classification distinguishes two cytological subtypes of bronchioloalveolar carcinoma (BAC): mucinous (M) and non-mucinous (NM). This distinction appears to be relevant in terms of clinical characteristics, prognostic and treatment effectiveness. We attempted to better characterize the molecular profile of M relative to NM. Experimental procedures: Bronchoalveolar lavage fluid (BALF) supernatants from M-BACs (n = 23) and NM-BACs (n = 11) were analyzed for 30 cytokines (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, FGF, PDGF, HGF, VEGF, Eotaxin, G-CSF, GM-CSF, IFNγ, CXCL-1, CXCL-8, CXCL-10, MCP-1, MIP-1α, MIP-1β, TNF-α, RANTES, VCAM-1) by Bio-Plex multiplex bead-based assay (BIORAD, Marne la Coquette, France). Cytokines of interest expression was studied on paraffin embedded specimens from surgical specimens (n = 45) using immunochemistry. EGFR and K-ras mutation analysis using direct PCR and Alk overexpression detection using immunochemistry were also performed. Univariate and multivariate analysis by Cox model was undertaken to identify the variables associated with a risk for shortened survival. Summary of results: Among the 30 chemokines analyzed, CXCL10 was the only one for which concentration was significantly higher in BALF supernatants from M-BAC (n = 23) compared to NM-BAC (n = 11) and control (n = 4) (p = 0.041). The cellular source of CXCL10 was not yet identified while CXCR3, its receptor, was expressed by tumor cells. CXCR3 was more frequently and more intensively expressed in M-BAC (n = 21) than in NM-BAC (n = 24) (52% vs 17%, p=0.023 and 52±16 vs 12±6, p = 0.047, respectively). EGFR mutation was never found in M-BAC (0%, 0/21) while present in 21% (5/24) of NM-BAC (p = 0.026). K-ras mutation and Alk overexpression did not differ between the two subtypes (2/21 vs 1/24, p &amp;gt; 0,05 and 3/21 vs 2/24, p &amp;gt; 0,05, respectively). The expression of CXCR3 was not associated with EGFR or K-ras mutation or Alk overexpression. In univariate analysis, factors associated with shorter survival were CXCL10 BALF concentration (HR=2.615, 95% CI: 1.102–6.206), PS &amp;gt; 0 (HR=1.308, 95% CI: 1.131–1.726) and bilateral extension (HR=2.914, 95% CI: 1.208–7.031). Multivariate analysis did not show any independent prognostic factor. Conclusions: Our results show a CXCL10/CXCR3 overexpression in M-BAC compared to NM-BAC and suggest an association between CXCL10 overexpression and shorter survival.
Plasma (1&amp;rarr;3)-β-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes
Authors: T Obayashi, T Kawai, M Yoshida, T Mori, H Goto, A Yasuoka, K Shimada, H Iwasaki, H Teshima, S Kohno, A Horiuchi, A Ito, H Yamaguchi
Journal: The Lancet (1995)
Regional end-systolic pressure-length relationships using a volume-loading technique in the intact pig heart.
Authors: W P Miller, A J Liedtke, S H Nellis
Journal: Circulation Research (1984)

The purpose of this study was to characterize left ventricular systolic elastances as derived from pressure-segment length and pressure-diameter relationships, and to compare the resulting regional and global elastances to known changes in inotropy. Left ventricular pressure-segment length and pressure-diameter were varied in a series of consecutive beats by means of a volume-loading technique, and both regional and global relationships at 20-msec intervals throughout systole were found to be nonlinear and to exhibit hysteresis. In eight animals, regional hysteresis was present after vagotomy, propranolol (1.0 mg/kg), and atropine (0.1 mg/kg), and was present no matter whether hearts were loaded by volume (45-60 ml/sec) or by pressure (partial aortic occlusion) over a similar range of left ventricular systolic pressures. Elastance was linearly approximated by the slope of the major axis of the hysteresis loops. In each instance, elastance increased to a maximum and then decreased, thus defining end-systole. In seven animals, maximum elastance-length and -diameter were compared before and after treatments with dobutamine (5-13 micrograms/kg per min) and propranolol (6-51 micrograms/kg per min), or after induction of global ischemia. Dobutamine increased maximum elastance-diameter by 37% (P less than 0.01) and maximum elastance-length by 159% (P less than 0.05). Propranolol decreased maximum elastance-diameter by 27% (P less than 0.05) and maximum elastance-length by 6% (P = NS). Global ischemia (50% reduction in coronary flow) did not significantly change either maximum elastance-diameter or -length. However, with ischemia, the diameter intercept of maximum elastance-diameter increased by 24% (P less than 0.025), and the time to maximum elastance-length decreased by 33% (P less than 0.01). Comparing all interventions, the percent changes in maximum elastance-length and -diameter related directly but with a low correlation coefficient (r = 0.49). These differences in regional and global elastance suggest a complex relationship between regional and global myocardial mechanics, and may not necessarily reflect specific changes in contractility.
Activity and mechanism of action of histone deacetylase inhibitors in trastuzumab resistant breast cancer.
Authors: S Radke, A Kumar, L Jones, DP Tuck, LN Harris
Journal: Cancer Research (2009)

Abstract Abstract #3060 Introduction: The Her2 antibody trastuzumab (T) is the first biological therapy that has proven the value of Her2 blockade in breast cancer. However, not all patients respond to trastuzumab and relapses occur after this treatment. Several studies suggest that histone deacetylase inhibitors (HDACis) are active in Her2-amplified breast cancer but none of them have addressed the role of HDACis in trastuzumab-resistant breast cancer. HDACis act by inhibiting the deacetylation of histones and other non-histone proteins such as Hsp90. Our goal is to study the activity, optimal sequencing and mechanism of action of HDACis in Her2-amplified cell lines, which demonstrate either de novo or acquired resistance to trastuzumab.&amp;#x2028; Methods: T-sensitive and Her2-overexpressing BT474 &amp; SkBr3, T-resistant BT474 and de novo T-resistant cell lines MDA-MB361, MDA-MB453, UACC812 and UACC893 were used for all experiments. The HDACi TSA (0-1uM) and trastuzumab at 100ug/mL were used for proliferation assays applying WST1 reagent (Roche). Western-immunoblotting was performed using cell lysates from untreated and treated cells. Proteolytic cleavage of caspase-3 and PARP was analyzed as indicator for apoptosis, Akt expression and phosphorylation for survival, Her2 and Erk1/2 expression and phosphorylation for proliferation and Hsp90 and Hsp70 were analyzed as key enzymes for chaperone activity.&amp;#x2028; Results: TSA inhibited proliferation in all cell lines [IC50 100-300 nM]. The addition of trastuzumab was antagonistic in de novo T-resistant cell lines MDA MB 453, UACC 812 and 893 but did not change the effect induced by TSA in acquired T-resistant cells (BT474_H100). Her2 expression decreased in TSA and TSA+T treated cells but not in cells treated with trastuzumab alone. Erk1/2 phosphorylation decreased in TSA and TSA+T treated cells but was not affected by trastuzumab alone. Similar phosphorylation patterns were observed regarding Akt. Of note, Akt, Erk1/2, Hsp90 and Hsp70 levels did not change. Finally, TSA induced caspase-3 and PARP cleavage when given as single agent or in combination with trastuzumab.&amp;#x2028; Discussion: This study suggests that HDACis are active in both trastuzumab-sensitive and de novo or acquired trastuzumab-resistant cell lines. However, use of trastuzumab together with TSA may be antagonistic in tumors that are resistant against trastuzumab. Further studies are required in these cell lines in order to elucidate the mechanism of resistance against trastuzumab and the mechanism of the here observed antagonistic effect between trastuzumab and TSA. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3060.
The Use of a Reference Allergenic Extract in the Evaluation of Allergen Products
Authors: L. Ingemann, H. Formgren, H. Løswenstein, H. Ipsen
Journal: Allergy (1985)

Two commercially available mugwort ( Artemisia vulgaris (Av)) pollen extracts Av‐ALK and Av‐PS were compared with a dialysed reference mugwort pollen extract (Av‐REF) by means of crossed immunoelectrophoresis (CIE), crossed radio immunoelectrophoresis (CRIE), RAST‐inhibition, RAST‐screening and skin prick test. Av‐ALK and Av‐PS both contained approximately half the number of precipitation arcs detectable in Av‐REF, and Av‐PS seemed to lack two intermediate allergens and two minor allergens, while Av‐ALK seemed to lack one minor allergen. The RAST‐inhibition curve obtained for Av‐PS did not parallel the curves obtained for Av‐ALK and Av‐REF, indicating that the allergen composition of Av‐PS differs from that of the others. Further, RAst‐screening experiments support the CIE observation that Av‐PS seemed to lack two of the intermediate allergens. The HEP values determined for Av‐ALK and Av‐PS diverge considerably from those stated by the manufacturers. The results obtained demonstrate that the outcome of a comparison between a reference allergenic extract and allergenic products depends very much on the method employed.
Absence of HIV Infection in Blood Donors with Indeterminate Western Blot Tests for Antibody to HIV-1
Authors: J. Brooks Jackson, Kristine L. MacDonald, Jane Cadwell, Carolyn Sullivan, William E. Kline, Margaret Hanson, Kim J. Sannerud, Susan L. Stramer, Nicola J. Fildes, Shirley Y. Kwok, John J. Sninsky, Robert J. Bowman, Herbert F. Polesky, Henry H. Balfour, Michael T. Osterholm
Journal: New England Journal of Medicine (1990)

To determine whether apparently healthy persons who have had repeatedly reactive enzyme immunoassays and an indeterminate Western blot assay for antibody to the human immunodeficiency virus type 1 (HIV-1) are infected with HIV-1 or HIV-2, we studied 99 such volunteer blood donors in a low-risk area of the country. The subjects were interviewed about HIV risk factors. Coded blood specimens were tested again for HIV-1 antibody (by two different enzyme immunoassays, a Western blot assay and a radioimmunoprecipitation assay) and for HIV-2 antibody by enzyme immunoassay, for HIV-1 by the serum antigen test, for HIV-1 by culture, for human T-cell leukemia virus Type I or II antibody by enzyme immunoassay, and for sequences of HIV DNA by the polymerase chain reaction. Of the 99 blood donors, 98 reported no risk factors for HIV-1 infection; 1 donor had used intravenous drugs. After a median of 14 months (range, 1 to 30) from the time of the initial test, 65 subjects (66 percent) were still repeatedly reactive for HIV-1 antibody on at least one immunoassay. In 91 subjects (92 percent) the Western blot results were still indeterminate, whereas in 8 they were negative. No donor met the criteria for a positive Western blot assay for HIV-1, and none had evidence of HIV-1 or HIV-2 infection on culture or by any other test. We conclude that persons at low risk for HIV infection who have persistent indeterminate HIV-1 Western blots are rarely if ever infected with HIV-1 or HIV-2.
BMA meeting: BMA reaffirms its policy of "soft consent" on organ transplantation
Authors: N. Hawkes
Journal: BMJ (2011)

BMA policy on organ transplantation was reaffirmed when the annual conference in Cardiff turned down the opportunity to change it.

A motion from Sharon Blackford, a consultant representing West Glamorgan Division, called for the abandonment of the presumed consent model which the BMA has backed for the past 12 years. This presumes that all potential donors have consented …
Molecular Microcircuitry Underlies Functional Specification in a Basal Ganglia Circuit Dedicated to Vocal Learning
Authors: Austin T. Hilliard, Julie E. Miller, Elizabeth R. Fraley, Steve Horvath, Stephanie A. White
Journal: Neuron (2012)

Similarities between speech and birdsong make songbirds advantageous for investigating the neurogenetics of learned vocal communication—a complex phenotype probably supported by ensembles of interacting genes in cortico-basal ganglia pathways of both species. To date, only FoxP2 has been identified as critical to both speech and birdsong. We performed weighted gene coexpression network analysis on microarray data from singing zebra finches to discover gene ensembles regulated during vocal behavior. We found ∼2,000 singing-regulated genes comprising three coexpression groups unique to area X, the basal ganglia subregion dedicated to learned vocalizations. These contained known targets of human FOXP2 and potential avian targets. We validated biological pathways not previously implicated in vocalization. Higher-order gene coexpression patterns, rather than expression levels, molecularly distinguish area X from the ventral striato-pallidum during singing. The previously unknown structure of singing-driven networks enables prioritization of molecular interactors that probably bear on human motor disorders, especially those affecting speech.
Abstract 2247: Ganoderma lucidum (Reishi) downregulates key proteins overexpressed in IBC and chemosensitizes EGFR-overexpressing cells to erlotinib.
Authors: Ivette Suarez-Arroyo, Raysa Rosario-Acevedo, Alexandra Aguilar-Pérez, Luis A. Cubano, Michelle M. Martínez-Montemayor
Journal: Cancer Research (2013)

Abstract Inflammatory Breast Cancer (IBC) is a unique and aggressive cancer where tumor spheroids invade the dermal lymphatics causing the inflammatory phenotype. IBC cell lines and human tissues overexpress plasma membrane proteins such as E-cadherin and Epidermal Growth Factor Receptor (EGFR), which are associated with maintaining tumor spheroid integrity, increased IBC tumor growth rate, invasion and metastasis. Since IBC tumor cell emboli are more efficient at forming metastases and are more resistant to chemo and radiotherapy than single cells, it seems feasible to prevent IBC with a compound that has the ability to disintegrate the cell spheroids. Our published data shows that the medicinal mushroom, Ganoderma lucidum (Reishi), inhibits IBC progression via disintegration of tumor spheroids. Thus, we aimed to investigate Reishi's in vitro and in vivo therapeutic potential in IBC, focusing on the regulation of E-cadherin and EGFR and its contribution to the IBC cellular response when treated with the EGFR Tyrosine Kinase Inhibitor (TKI), erlotinib (commercially known as Tarceva®). Herein, we show that Reishi downregulates E-cadherin and EGFR abundance in vitro, significantly reduces tumor growth by 58%, and downregulates in vivo EGFR, and E-cadherin protein expression. Moreover, a synergistic effect is observed when erlotinib and Reishi are used simultaneously after 72 hours of treatment. Since Reishi downregulates the expression of E-cadherin and EGFR, our subsequent investigations will focus on the identification of PM proteins using stable isotope labeling with amino acids in cell culture (SILAC). Our results provide evidence that Reishi downregulates key proteins overexpressed in IBC, and chemosensitizes IBC cells to erlotinib therapy, highlighting its anti-IBC-therapeutic potential. This project was sponsored by Title V PPOHA US Dept of Education #P031M105050 to UCC, NIH/RCMI #2G12RR003035 to UCC, NIH/INBRE #5P20RR016470 to UPR/UCC, NIH/NCRR #U54RR026139 to UPR/UCC, and a research donation from the Commonwealth of Puerto Rico to UCC-Centro Universitario de Medicina Integral y Complementaria (CUMIC) / MMM. Citation Format: Ivette Suarez-Arroyo, Raysa Rosario-Acevedo, Alexandra Aguilar-Pérez, Luis A. Cubano, Michelle M. Martínez-Montemayor. Ganoderma lucidum (Reishi) downregulates key proteins overexpressed in IBC and chemosensitizes EGFR-overexpressing cells to erlotinib. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2247. doi:10.1158/1538-7445.AM2013-2247
Delayed Drug Hypersensitivity Reactions
Authors: Werner J. Pichler
Journal: Annals of Internal Medicine (2003)

Immune reactions to small molecular compounds, such as drugs, can cause a variety of diseases involving the skin, liver, kidney, and lungs. In many drug hypersensitivity reactions, drug-specific CD4+ and CD8+ T cells recognize drugs through their alphabeta T-cell receptors in an MHC-dependent way. Drugs stimulate T cells if they act as haptens and bind covalently to peptides or if they have structural features that allow them to interact with certain T-cell receptors directly. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthema reveal that distinct T-cell functions lead to different clinical phenotypes. In maculopapular exanthema, perforin-positive and granzyme B-positive CD4+ T cells kill activated keratinocytes, while a large number of cytotoxic CD8+ T cells in the epidermis is associated with formation of vesicles and bullae. Drug-specific T cells also orchestrate inflammatory skin reactions through the release of various cytokines (for example, interleukin-5, interferon) and chemokines (such as interleukin-8). Activation of T cells with a particular function seems to lead to a specific clinical picture (for example, bullous or pustular exanthema). Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T-cell reactions, which through the release of certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4+ or CD8+ T cells (type IVc) seem to participate in all type IV reactions.
Letter: Glucagon in management of perforated oesophagus.
Authors: R Pickard
Journal: BMJ (1974)

the experience of a sighted person.Blind- foldinig will give some idea of the physical disabilities of the blind but no idea of the heightening of his other senses which he may eventually employ.It cannot reproduce the emotional background.We are so used to "eye to eye" relationships with our fellows that we inevitably feel insecure at our first meeting with someone with whom this is impossible.As for teaching, I do not foresee any im- provement in the situation as less and less time becomes available for specialized teach- ing of this sort.The task of equipping the family doctor ito anticipate the odd ophthalmnic disaster is bound to take pre- cedence over training him for all but the most rudimentary aspects of care and rehabilitation of the blind and partiallysighted.Nevertheless, the family practitioner musit have confident recourse to others who can supply this expertise, and such others will be grateful to Dr. Shaw for helping their understanding.
Decreased collagen mRNA and regression of cardiac fibrosis in the ventricular myocardium of the tight skin mouse following thyroid hormone treatment
Authors: J. Yao, M. Eghbali
Journal: Cardiovascular Research (1992)

Objective: The aim was to study the effect of thyroid hormone on collagen gene expression in the myocardium of the tight skin mouse (TSK), a genetic model of myocardial fibrosis. Methods: Heterozygous male (TSK/+) (n=20) and normal (+/+) homozygous mice (n=20), 1.5-2 months old of the C57 BL/6 strain were studied. Ventricular hypertrophy following thyroid hormone treatment (L-thyroxine, 10 μg·100 g−1 body weight daily intraperitoneally) was examined by measurement of the heart weight/body weight ratios and histological changes. Expression of fibrillar collagen types I and III in the ventricular myocardium was examined by measurement of the abundance of their respective mRNAs. Collagen synthesis was examined by measurement of hydroxyproline. Deposition of collagen types was evaluated by immunofluorescence staining. Expression of non-collagenous proteins, sarcomeric and cytoskeletal actin, was measured at the mRNA level. Results: After 12 days of treatment ventricular hypertrophy was induced in the heart of the TSK mice. The results of northern hybridisation analyses showed that in the hearts of TSK mice 24 h after thyroxine treatment the abundance of mRNA for pro α2 (I) collagen was decreased by 32% (p<0.05), pro α1 (III) collagen by 47% (p<0.002), cytoskeletal actin by 50% (p<0.005), and sarcomeric actin mRNA by 34% (p<0.01) compared to the untreated TSK mice. The abundance of mRNA for pro α2 (I) and pro α1 (III) collagens in the thyroxine treated TSK mice were nearly comparable to that in normal homozygous mice. In TSK mice which were treated for 12 d, collagen content of the ventricular myocardium, as determined by hydroxyproline measurements, was decreased by 22.5% (p<0.01) compared to that in the heart of normal homozygous mice. Conclusions: Effects of thyroid hormone on ventricular gene expression in TSK mice result in a diminished collagen mRNA and collagen content and the disappearance of cardiac fibrosis. Thyroid hormone may selectively prevent the induction of cardiac fibrosis and play an important role in regression of cardiac fibrosis via endocrine pathways.
EXPERIENCES WITH RADIOSULFATE IN THE ESTIMATION OF PHYSIOLOGIC EXTRACELLULAR WATER IN HEALTHY AND ABNORMAL MAN 12
Authors: Robert J. Ryan, Luke R. Pascal, Tohru Inoye, Lionel Bernstein
Journal: Journal of Clinical Investigation (1956)

We have been interested in studying the changes in extracellular fluid volume in patients undergoing acute heat stress.Attempts to apply the inulin method to our needs were fruitless because of the prolonged time period required for equilibrium.Walser's radiosulfate method (1, 2) had appeal since it appeared suitable for repeated determina- tions within a short period of time.Walser has suggested that within 15 to 20 min- utes following ai single intravenous injection, radio- sulfate reached an apparent equilibrium between the vascular and interstitial spaces (1,2).He showed that the calculated volume of distribution of radiosulfate increased with time (1, 2) and that this increase could not be accounted for by urinary excretion (1, 2), fecal loss (3), or penetration of the muscle chloride space (4).He proposed that the 18-minute volume of distribution of radiosul- fate could be used as an index of functioning extra- cellular fluid volume (1, 2).The present report, dealing with the radiosul- fate method, confirms and extends many of Walser's observations.In addition, it points out the desirability of calculating a "zero time" rather than an 18-minute volume of distribution, and pro- poses a modification of existing ways of calculating the "zero time" space. METHODSA. Subjects: Radiosulfate spaces were determined on 33 healthy individuals: eleven (Nos.1-11) young, mus- cular soldiers; nine (Nos.12-20) young, male medical students and physicians; five (Nos.21-25) ambulatory, elderly males; and eight (Nos.26-33) ambulatory, elderly females.Four patients with abnormalities of water metabolism were studied: two (Nos.34, 35) were de- 1 Supported in part by a grant from the U. S. Public Health Service.2The opinions expressed in this paper are those of the authors and do not necessarily represent the official views of any government agency.hydrated and two (Nos.36, 37) had ascites without peripheral edema.In five subjects the radiosulfate space was redetermined at various intervals, ranging from 1 to 30 days, during which they continued their usual daily activities.Each of the eleven soldiers had a second determination following a three-week period of paratroop training.B. Procedure: All subjects were studied in the morn- ing after a twelve-hour fast.They were allowed water ad libitum during the preceding day and were given 200 ml. of water every two hours during the course of the test.Approximately 100 microcuries of S5 as carrier-free sodium sulfateB were injected intravenously, from a cali- brated syringe, over a period of one minute.An aliquot