tbuckley/cabot-search huggingface dataset:
Abstract 2467: Acidic pericellular pH increases contribution of cathepsin B to invasiveness of a human breast carcinoma cell line
Authors: Jennifer M. Rothberg, Mathew S. Bogyo, Bonnie F. Sloane
Journal: Cancer Research (2012)

Abstract Among the non-cellular microenvironmental factors that may contribute to malignancy of solid tumors is an acidic peritumoral pH (pHe). We have shown that this induces secretion of the lysosomal cysteine protease, cathepsin B. The object of the present study was to further examine the effect of a slightly acidic pericellular pH (i.e., pHe 6.8) on degradation of collagen IV and the activity and secretion of proteolytic enzymes, in particular cathepsin B. For these studies, we used: 1) a highly malignant human breast carcinoma line, MDA-MB-231-RFP; 2) a 3D reconstituted basement membrane overlay culture model; 3) a live cell confocal microscopy assay for imaging proteolysis and detecting active cathepsin B via an activity based probe, GB123; 4) a protocol for quantification of proteolysis on a per cell basis; 5) and fluorometric real-time and plate-reader assays for measuring cathepsin B activity. The live cell proteolysis assay confirmed that degradation of collagen IV by the MDA-MB-231 cells was consistently higher at a slightly acidic pHe and was decreased by a highly selective cathepsin B inhibitor, CA074. A dramatic increase in cathepsin B secretion from MDA-MB-231 cells was observed upon exposure to an acidic pHe, as assessed by assays of conditioned media and analysis of secretion in real-time. Our results are consistent with the hypothesis by Gillies and colleagues of “acid-mediated invasion” in tumors and suggest a role for cathepsin B in promoting degradation of collagen IV and thereby tumor invasiveness in the acidic peritumoral microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2467. doi:1538-7445.AM2012-2467
Proteomic analysis of skin irritation reveals the induction of HSP27 by sodium lauryl sulphate in human skin
Authors: I.L.A. Boxman, P.J. Hensbergen, R.C. Van Der Schors, D.P. Bruynzeel, C.P. Tensen, M. Ponec
Journal: British Journal of Dermatology (2002)

Summary Background There is an increasing need for screening of mild irritants in vitro to reduce animal testing. Objectives Proteomics were used to search for new markers of which the expression changes after mild irritation. Methods Sodium lauryl sulphate (SLS) was applied topically on excised human skin. Epidermal proteins were isolated from SLS-treated skin specimens that showed hardly any morphological changes. The proteins were analysed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and proteins that significantly increased or decreased after SLS treatment in a dose-dependent way were characterized by mass spectrometry. Subsequently, immunohistochemistry was performed on skin samples treated with SLS in vivo and nonanoic acid (NAA) or benzalkonium chloride (BC) in vitro to evaluate one of the identified proteins for its predictive value. Results We identified seven proteins as potentially new epidermal markers for skin irritation. Among these seven proteins, the 27 kDa heat shock protein (HSP27) was identified as the most prominently upregulated protein. A strong nuclear HSP27 staining was seen in the SLS-treated skin, whereas in the vehicle controls only cytoplasmic staining was observed. Moreover, nuclear staining was also observed after topical application of SLS in vivo and after exposure to NAA and BC in vitro. Conclusions Our findings suggest that HSP27 may serve as a sensitive marker of skin irritation and eventually as a novel tool in clinics for testing the sensitivity of the patient for a panel of irritants.
Combined mTOR Inhibition and OX40 Agonism Enhances CD8+ T Cell Memory and Protective Immunity Produced by Recombinant Adenovirus Vaccines
Authors: Jennifer D Bassett, Stephanie L Swift, Heather VanSeggelen, Joanne A Hammill, AJ Robert McGray, Carole Evelegh, Yonghong Wan, Jonathan L Bramson
Journal: Molecular Therapy (2011)

The memory CD8(+) T cell population elicited by immunization with recombinant human adenovirus serotype 5 (rHuAd5) vaccines is composed primarily of effector and effector memory cells (T(EM)) with limited polyfunctionality. In this study, we investigated whether treatment with immunomodulators could enhance and/or redistribute the CD8(+) memory population elicited by rHuAd5. Vaccination in combination with both rapamycin (to modulate differentiation) and an OX40 agonist (to enhance costimulation) increased both the quantity and polyfunctionality of the CD8(+) memory T cell population, with expansion of the T(EM) and memory precursor populations. Furthermore, this intervention enhanced protection against multiple virus challenges. Attenuation of adenovirus transgene expression was required to enable the combination rapamycin + OX40 agonist immunomodulatory treatment to further enhance skewing towards central memory formation, indicating that persistence of antigen expression ultimately limits development of this memory population following rHuAd5 immunization. These results demonstrate that during the expansion phase following adenovirus immunization, the level of mammalian target of rapamycin (mTOR) activity, the amount of costimulation and the duration of antigen availability act together to define the magnitude, phenotype, and functionality of memory CD8(+) T cells. Modulation of these factors can be used to selectively manipulate memory formation.
Induction of plasminogen activator inhibitor by products released from platelets.
Authors: S Fujii, B E Sobel
Journal: Circulation (1990)

Activation of platelets and augmentation of plasma plasminogen activator inhibitor (PAI) type I activity accompany acute myocardial infarction. To determine whether the two may be related, platelet compounds including epidermal growth factor and transforming growth factor beta as well as platelet lysates were studied in rabbits in vivo. After intravenous infusion of epidermal growth factor (1 and 5 micrograms/kg), plasma PAI activity increased sevenfold and 20-fold, peaking at 2 hours. After infusions of transforming growth factor beta (0.2 and 0.5 microgram/kg), plasma PAI activity increased sevenfold and 12-fold but peaked more slowly (at 5 hours). After infusion of platelet lysates (lysates from 2.8 and 5.6 X 10(8) platelets/kg), the increase was 19-fold and 35-fold, with a peak at 4 hours. Platelet lysates induced a pronounced increase of plasma PAI type 1 messenger RNA (Northern blots) in aorta, liver, and myocardium. Anti-transforming growth factor beta neutralizing antibody markedly attenuated the plasma PAI increase. Concentrations in plasma of fibrinogen and alpha 2-antiplasmin were virtually unaffected under all conditions. Thus, platelet-associated growth factors and platelet lysates, shown previously to increase plasma PAI type 1 messenger RNA expression and protein production in cultured hepatocytes and vascular endothelial cells in vitro, augment plasma PAI in vivo as well. Accordingly, activation of platelets and release of platelet-associated growth factors appear to contribute to the increased plasma PAI seen after myocardial infarction.
Tobacco company claims that smokers help the economy
Authors: Z. Kmietowicz
Journal: BMJ (2001)

Smokers are doing their country a huge favour by boosting tax revenue, dying early, and not drawing a pension, according to a report by the tobacco giant Philip Morris.

Officials in the Czech Republic have been given an analysis, commissioned by the cigarette manufacturer, which suggests that the economic benefits of smoking to the country far outweigh the harmful effects. Rather than being a drain on healthcare resources, smoking actually saves the country more than £100m ($140m) …
Assessment and Treatment of Pervasive Anxiety
Authors: Philip Snaith
Journal: Psychotherapy and Psychosomatics (1986)

Definitions of the central symptoms of anxiety disorders are given and these are followed by the principles underlying assessment; a discussion of rating scales for the detection and measurement of morbid degrees of anxiety follows. The important points in assessment prior to therapy are outlined and emphasis is placed on the possibility of distinguishing biogenic (endogenous) anxiety states from the more usual psychogenic forms of anxiety disorder. This distinction is of major importance when devising the therapeutic plan: biogenic depressive states, of which the early stage of panic disorder is one form, are resistant to psychotherapeutic intervention but may respond to treatment with antidepressant drugs. The principles of brief psychotherapeutic intervention are outlined with emphasis on the two central themes underlying successful therapy: the development of self-control and the exposure of the patient to anxiety in the setting of the therapeutic programme.
mother's response
Authors: D. Laverty
Journal: BMJ (2003)

My husband and I had been estranged for about six years when our son became ill. Despite our separation, we always communicated about decisions relating to our son's care.

The night when he began bleeding is etched in my memory. The most poignant thing is my recollection of my son's face. He looked absolutely terrified. After his condition stabilised, we (the family) left the room to discuss the situation with the doctors. They explained that if the procedure was not …
Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy
Authors: Manuel Tsiang, James F. Rooney, John J. Toole, Craig S. Gibbs
Journal: Hepatology (1999)

In a recent phase II clinical study, 13 chronic hepatitis B-infected patients treated daily with 30 mg adefovir dipivoxil for 12 weeks displayed a median 4.1-log10 decrease in plasma hepatitis B virus (HBV)-DNA levels. The decline of viral load during therapy displayed a biphasic kinetic profile that was modeled to determine the efficacy of inhibition of viral production, as well as kinetic constants for the clearance of free virus and the loss of infected cells. Viral production was suppressed with an efficacy of 0.993 +/- 0.008, indicating that only 0.7% of viral production persisted during therapy. The initial, faster phase of viral load decline reflects the clearance of HBV particles from plasma with a half-life of 1.1 +/- 0.3 days, translating to a 48% daily turnover of the free virus. The second, slower phase of viral load decline closely mirrors the rate-limiting process of infected cell loss, with a half-life of 18 +/- 7 days. The duration of therapy required to completely eliminate the virus from plasma or suppress it to levels sufficient to induce seroconversion is a function of the half-life of the free virus, the half-life of infected cells, and the efficacy of inhibition of virus production from infected cells. These quantitative analyses provide a more detailed picture of the dynamics of HBV infection and therapy, and can be used to compare the efficacy of various doses and inhibitors of HBV replication for the treatment of HBV infections.
Serum Protein-Bound Carbohydrates in Rheumatic Disease: II. EVALUATION OF ACTIVITY IN RHEUMATOID ARTHRITIS
Authors: L. E. Bottiger, E. Malmquist, B. Olhagen
Journal: Annals of the Rheumatic Diseases (1964)

SERUM PROTEIN-BO UND CARBOHYDRATES.Il.Los carbohidratos ligados con proteinas en las enfermedades reumaticas 1. Resultados de analisis diferenciales en varios disturbios reumaticos SUMARIO Los carbohidratos ligados con proteinas (hexosas, hexosaminas y acidos sialicos) fueron analizados en el suero completo de 187 sujetos con diferentes enferme- dades reumaticas.En 7 casos de artritis reumatoide grave o de lupus eritematoso diseminado se estudi6 la fracci6n proteica despues de separarla por electroforesis.En todas las enfermedades estudiadas se not6 un aumento considerable de carbohidratos ligados con proteinas pero no se vieron alteraciones especificas de estos.Todas las separaciones electroforeticas mostraron la existencia de una raz6n constante entre los carbohidratos y las proteinas.
Effects of Hyaluronidase Administration on Myocardial Ischemic Injury in Acute Infarction
Authors: Peter R. Maroko, Dennis M. Davidson, Peter Libby, Arthur D. Hagan, Eugene Braunwald
Journal: Annals of Internal Medicine (1975)

The effect of hyaluronidase on myocardial ischemic injury was examined in 13 patients with acute myocardial infarction, and the results were compared with 11 patients who did not receive hyaluronidase. A 35-electrode precordial mapping method was used to assess the rate of resolution of ST segment elevations. In the 11 control patients, the sum of ST segment elevations (ΣST) fell after 2 hours to an average of 93.5% ± 17.3% (SEM) and after 24 hours to 89.6% ± 7.6% of the initial values, while the number of electrodes exhibiting ST segment elevations exceeding 0.1 mV (NST) fell to 98.0% ± 12.3% and 94.3% ± 10.4% of the initial values respectively. In the hyaluronidase-treated group, at the same time ΣST fell significantly more (P < 0.05), to 54.1% ± 5.0% and 51.3% ± 11.8% and NST was also more markedly reduced (P < 0.05) to 50.7% ± 7.8% and 50.1% ± 12.4%, thus indicating that hyaluronidase can accelerate the reduction of myocardial ischemic injury in patients with acute myocardial infarction.
Piezoelectric lithotripsy (EPL) of gallstores (GS)
Authors: J.M. Herrerias, A. Garcia-Donas, C. Carrasco, J. Guerrero, J.C. Rosado, J.H. Gercia, M. Jieenez, J.D. Delgado, P. Hergueta
Journal: Journal of Hepatology (1991)
Recovery from Acute Renal Failure After 23 Days of Anuria
Authors: Joseph C. Dougherty
Journal: JAMA (1963)

PROLONGED SURVIVAL of human beings without significant renal function has been made possible by repeated treatments with the artificial kidney.<sup>1-7</sup>Recoveries have been recorded in patients with acute renal failure after 34 days of oliguria,<sup>3,5</sup>but recovery after prolonged periods of total urinary suppression has been distinctly rare and may indicate a prognostic distinction between oliguria (less than 400 ml a day) and anuria (less than 25 ml a day). We recently treated a patient who developed acute renal failure after abortion complicated by Clostridium welchii sepsis. The 23-day-long anuria seemed to indicate an extremely poor prognosis and may have been related to delay in eradicating a residual uterine abscess which was a site of Clostridial infection. Nevertheless, the patient finally entered a short oliguric and then a diuretic phase, and ultimately recovered. Although other cases of anuria lasting from 22½ to 30 days without dialytic therapy have
Letter: Deaths during dentistry.
Authors: J Bourne
Journal: BMJ (1975)

The present study was undertaken to identify trigeminal premotor interneurons that become activated during carbachol-induced active sleep (c-AS). Their identification is a critical step in determining the neural circuits responsible for the atonia of active sleep. Accordingly, the retrograde tracer cholera toxin subunit B (CTb) was injected into the trigeminal motor nuclei complex to label trigeminal interneurons. To identify retrograde-labeled activated neurons, immunocytochemical techniques, designed to label the Fos protein, were used. Double-labeled (i.e., CTb<sup>+</sup>, Fos<sup>+</sup>) neurons were found exclusively in the ventral portion of the medullary reticular formation, medial to the facial motor nucleus and lateral to the inferior olive. This region, which encompasses the ventral portion of the nucleus reticularis gigantocellularis and the nucleus magnocellularis, corresponds to the rostral portion of the classic inhibitory region of Magoun and Rhines (1946). This region contained a mean of 606 ± 41.5 ipsilateral and 90 ± 32.0 contralateral, CTb-labeled neurons. These cells were of medium-size with an average soma diameter of 20–35 μm. Approximately 55% of the retrogradely labeled cells expressed<i>c-fos</i> during a prolonged episode of c-AS. We propose that these neurons are the interneurons responsible for the nonreciprocal postsynaptic inhibition of trigeminal motoneurons that occurs during active sleep.
Endogenous Na,K Pump Ligands Are Differentially Regulated During Acute NaCl Loading of Dahl Rats
Authors: Olga V. Fedorova, Edward G. Lakatta, Alexei Y. Bagrov
Journal: Circulation (2000)

Background —Two mammalian digitalis-like factors, an ouabain-like compound (OLC) and marinobufagenin (MBG), exhibit specificity to α-3 and α-1 Na + ,K + -ATPase isoforms, respectively. We compared regulation of MBG and OLC by acute NaCl loading in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. Methods and Results —An intraperitoneal NaCl load (0.8 g/kg) was given to adult male rats (24 DS and 24 DR). Diuresis, natriuresis, renal excretion, and tissue levels of MBG and OLC were measured. Inhibition of renal Na + ,K + -ATPase by MBG and ouabain was compared in DS, DR, and Wistar rats. DS (versus DR) exhibited a smaller peak (2 hours) natriuretic response (1.34±0.10 versus 2.08±0.14 mmol · kg − 1 · h − 1 ; P &lt;0.01), despite a greater plasma Na + (153±2 versus 145±1 mmol/L; P &lt;0.01). In DS and DR, pituitary, adrenal, and plasma OLC exhibited transient 2-fold to 3-fold increases, followed by a decrease to baseline levels. Plasma and adrenal MBG doubled in both strains within 1 hour of NaCl loading and remained elevated. Eight-hour MBG excretion in DS was 4-fold greater than in DR (15.8±0.8 versus 3.6±0.4 pmol; P &lt;0.01), whereas OLC excretion in DS was only 30% greater than in DR (16.1±1.1 and 11.9±0.8 pmol; P &lt;0.05). Kidney Na + ,K + -ATPase (α-1 isoform) from Wistar rats and DS exhibited greater sensitivity to MBG than to ouabain. Conclusions —NaCl loading of DS causes transient increase in OLC but sustained increases in MBG tissue levels and excretion. We hypothesize that increased MBG production occurs in an attempt to compensate for genetically impaired pressure-natriuresis mechanisms.
A piece of my mind. Food for thought
Authors: J. D. Wassersug
Journal: JAMA (1988)

Knowing that I had been invited to a drug company—sponsored lecture cum gourmet dinner, a couple of my colleagues asked me if I would drive them to the affair, since they were both hesitant about driving at night. They were in their mid80s while I, at that time, was a mere youngster of 74. Compared with them, I still had some of the bravado of my youth. So, I was the chauffeur while my two old friends sat in the back seat discussing, mostly, the state of their health. Both of them admitted to being in good health and requiring no special medicines or treatments. Both were almost smug in their self-satisfaction in having been able to maintain an active medical practice for more than 50 years. What worried them most, however, was their mode of dying. Each confessed to having prayed fervently and frequently for a quick and easy
Abstract 5513: An immune-active tumor microenvironment favors clinical response to ipilimumab
Authors: Rui-Ru Ji, Omid Hamid, Scott D. Chasalow, John Cogswell, Suresh Alaparthy, David Berman, Vafa Shahabi
Journal: Cancer Research (2011)

Abstract Ipilimumab, a fully human monoclonal antibody specific to CTLA-4, has shown improvement in overall survival in previously treated advance melanoma patients. As a consequence of blockade of the T cell regulatory molecule CTLA-4, ipilimumab treatment is associated with proliferation and activation of peripheral T cells. An important factor for impacting tumor growth however, is whether these T cells can successfully migrate into the tumor. In order to gain a better understanding of the various tumor-associated components that determine the clinical activity of ipilimumab in melanoma tumors, Affymetrix gene expression profiling and pathway analysis were retrospectively performed on 46 primary or metastatic melanoma tumors, collected in a complete phase II clinical trial in advanced melanoma patients. In biopsies obtained at baseline (before treatment), there were 361 differentially genes expressed (≥ 1.5 fold difference in expression, p ≤ 0.01); most over-expressed transcripts and pathways associated with favorable clinical activity were immune-related. Furthermore, differential analysis of mRNA from pre- and post-treatment tumor biopsies pointed to additional increase in the expression of these genes after treatment. Interestingly, ipilimumab treatment was associated with down-regulation of a number of melanoma-associated transcripts in the tumors within a short time (3 weeks after the first dose). Our preliminary results suggest that high pre-existing immune-activity favors clinical response to ipilimumab. These analyses also provide a list of candidate biomarkers with potential predictive value for response to ipilimumab, to be confirmed in a larger, placebo controlled clinical trial. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5513. doi:10.1158/1538-7445.AM2011-5513
Assessing the cancer risk from environmental PCBs.
Authors: V J Cogliano
Journal: Environmental Health Perspectives (1998)

A new approach to assessing the cancer risk from environmental polychlorinated biphenyls (PCBs) considers both toxicity and environmental processes to make distinctions among environmental mixtures. New toxicity information from a 1996 cancer study of four commercial mixtures strengthens the case that all PCB mixtures can cause cancer, although different mixtures have different potencies. Environmental processes alter PCB mixtures through partitioning, chemical transformation, and preferential bioaccumulation; these processes can increase or decrease toxicity considerably. Bioaccumulated PCBs are of greatest concern because they appear to be more toxic than commercial PCBs and more persistent in the body. The new approach uses toxicity studies of commercial mixtures to develop a range of cancer potency estimates and then considers the effect of environmental processes to choose appropriate values for representative classes of environmental mixtures. Guidance is given for assessing risks from different exposure pathways, less-than-lifetime and early-life exposures, and mixtures containing dioxinlike compounds.
Automated system for the measurement of airways resistance, lung volumes, and flow-volume loops.
Authors: P J Chowienczyk, P J Rees, T J Clark
Journal: Thorax (1981)

Using a digital computer and body plethysmograph measurements of airways resistance, lung volumes, and flow-volume loops may be obtained from a single manoeuvre performed by the patient. All the measurements together with a display of the flow-volume loop are displayed within 10 seconds of the patient completing the manoeuvre. The system appears to offer considerable advantages in speed, objectivity, and reproducibility when compared with conventional methods.