tbuckley/cabot-search huggingface dataset:
Proteomic Analysis of Bronchoalveolar Lavage Fluid: Effect of Acute Exposure to Diesel Exhaust Particles in Rats
Authors: John A. Lewis, K. Murali Krishna Rao, Vince Castranova, Val Vallyathan, William E. Dennis, Paul L. Knechtges
Journal: Environmental Health Perspectives (2007)

BackgroundInhalation of diesel exhaust particles (DEPs) is characterized by lung injury and inflammation, with significant increases in the numbers of polymorphonuclear leukocytes and alveolar macrophages. This influx of cellular infiltrates is associated with the activation of multiple genes, including cytokines and chemokines, and the production of reactive oxygen species.ObjectiveThe pathogenesis of the lung injury is not fully understood, but alterations in the presence or abundance of a number of proteins in the lung have been observed. Our objective in this study was to further characterize these changes and to ask whether additional changes could be discerned using modern proteomic techniques.MethodsThe present study investigates global alterations in the proteome of bronchoalveolar lavage fluid taken from rats 1, 7, or 30 days after exposure to 5, 35, or 50 mg/kg of animal weight of DEPs.ResultsAnalysis by surface-enhanced laser desorption/ionization–time of flight mass spectrometry identified two distinct peaks that appeared as an acute response postexposure at all doses in all animals. We identified these two peaks, with mass to charge ratios (m/z) of 9,100 and 10,100, as anaphylatoxin C3a and calgranulin A by additional mass spectral investigation using liquid chromatography coupled to mass spectrometry.ConclusionsWith this approach, we found a number of inflammatory response proteins that may be associated with the early phases of inflammation in response to DEP exposure. Further studies are warranted to determine whether serum levels of these proteins could be markers of diesel exhaust exposure in workers.
Regulation of antigen-induced human T-lymphocyte responses by calcineurin antagonists
Authors: Sarah E. Pacocha, Alfonso Oriente, Shau-Ku Huang, David M. Essayan
Journal: Journal of Allergy and Clinical Immunology (1999)

Background: Cyclosporin A (CS) and tacrolimus (FK506, FK) are calcineurin antagonists used widely as T-cell immunosuppressants; however, their relative efficacy on antigen-stimulated T-cell subsets remains undefined. Objective: We have examined the effects of CS and FK on antigen-driven proliferation and cytokine generation from human PBMCs and T-cell clones. Methods: Proliferation was assessed by tritiated thymidine incorporation. Cytokine generation was assessed by reverse transcription–PCR and ELISA. Results: Ragweed- and tetanus toxoid–driven proliferation of PBMCs was down-regulated equally by CS or FK. Gene expression for proinflammatory cytokines (IL-4, IL-5, IL-13, and IFN-γ) assessed by reverse transcription–PCR was down-regulated in a concentration-dependent manner by either drug. Antigen-induced proliferation of ragweed-specific Th0, Th1, or Th2 clones was inhibited by either CS or FK. Cytokine gene expression and protein secretion into culture supernatants (IL-4, IL-5, IL-13, and IFN-γ) were down-regulated in a concentration-dependent manner by either CS or FK in all relevant T-cell subsets. Interestingly, down-regulation of IL-5 protein generation from Th0 and Th2 clones was consistently less sensitive to either drug than was the effect on either IL-4 or IL-13 protein generation. Conclusion: CS and FK promote equivalent down-regulation of Th0, Th1, and Th2 responses; however, IL-5 generation is relatively insensitive to the immunomodulatory effects of calcineurin antagonists. (J Allergy Clin Immunol 1999;104:828-35.)
Comparative Effectiveness of Budesonide/Formoterol Combination (BFC) and Fluticasone/Salmeterol Combination (FSC) Among Asthma Patients
Authors: Setareh Williams, Ozgur Tunceli, David Kern, Ned Pethick, Hanaa Elhefni, Catrin Wessman, Siting Zhou, Frank Trudo
Journal: Journal of Allergy and Clinical Immunology (2013)
Intravenous Recombinant Tissue Plasminogen Activator (rt-PA) and Urokinase in Acute Myocardial Infarction: Results of the German Activator Urokinase Study (GAUS)
Authors: Karl-Ludwig Neuhaus, Ulrich Tebbe, Martin Gottwik, Michael A.J. Weber, Werner Feuerer, Walter Niederer, Winfried Haerer, Frank Praetorius, Klaus-Dieter Grosser, Wolfgang Huhmann, Hans-Wilhelm Hoepp, Guenter Alber, Abdohlhamid Sheikhzadeh, Berthold Schneider
Journal: Journal of the American College of Cardiology (1988)
Detection of Neisseria gonorrhoeae-Reply
Authors: Efstratios Demetriou
Journal: JAMA (1985)

<h3>In Reply.—</h3> We appreciate Dr White's comments regarding our recently published article. We agree that the enzyme immunoassay (EIA) is useful for detecting<i>N gonorrhoeae</i>antigen only in cervical and urethral specimens. (Our own unpublished data with rectal specimens showed that EIA lacked adequate specificity when compared with culture.) Alternately, culture is useful for detecting only those strains of<i>N gonorrhoeae</i>that are culturable under given laboratory conditions. One must analyze the situation relating to specimen handling and transport and the prevalence of vancomycin-sensitive strains before judging the relative merits of culture<i>v</i>EIA for diagnosis of gonorrhea in their particular setting. In our discussion we made the point that EIA offers no clear advantage when compared with a Gram's stain of urethral material from males. We caution that Gram's stain of endocervical secretions from females lacks sufficient sensitivity<sup>1</sup>and cannot be used in place of culture or EIA. We
Use of an anti-low density lipoprotein receptor antibody to quantify the role of the LDL receptor in the removal of chylomicron remnants in the mouse in vivo.
Authors: S Y Choi, L G Fong, M J Kirven, A D Cooper
Journal: Journal of Clinical Investigation (1991)

Lipoproteins are removed from the plasma by LDL receptor-dependent and -independent pathways. The relative contribution of these has been established for LDL by using modified lipoproteins, but this has not been possible for apoE-rich lipoproteins, such as chylomicron remnants. To do this, we used a monospecific antibody to the rat LDL receptor. The antibody was injected intravenously into mice followed by 125I-lipoproteins. Blood samples were obtained sequentially and radioactivity measured to determine the plasma clearance of the lipoproteins. The animals were then sacrificed and the tissues removed, dried, and the radioactivity measured to determine tissue uptake. An albumin space was also measured to correct for blood trapping. With 125I-human LDL, approximately 50% of the injected dose was cleared in 180 min. This was reduced to 30% by the antibody and this was identical to the disappearance of reductively methylated LDL. This is a lower estimate of LDL-mediated uptake (40%) than in other species. LDL uptake per gram tissue was similar for the liver and the adrenal gland and was approximately 50% LDL receptor-dependent in both tissues. With 125I-chylomicron remnants, clearance was much more rapid with approximately 50% cleared in 5 min. By agarose gel electrophoresis, radioactivity was not transferred from chylomicron remnants to other lipoprotein classes. Chylomicron remnants with label on only apoB or in 3H-cholesterol esters showed a similar pattern. Combining the estimates of the three labeling procedures, approximately 35% of the 30 s and 25% of the 5 min chylomicron remnant disappearance was LDL receptor dependent. The liver, per gram tissue, took up five times as much radioactivity as the adrenal gland. At 5 min, at least 50% of this was LDL receptor-dependent in liver and 65% in adrenal gland. We conclude that the LDL receptor plays a major, and somewhat similar quantitative role in the clearance of both LDL and chylomicron remnants in the mouse. However, at least in the mouse, non-LDL receptor-mediated lipoprotein clearance is quantitatively important and is also very rapid for chylomicron remnants. Thus, for chylomicron remnants, it can easily compensate for LDL receptors if they are blocked or absent. Further, the tissue distribution of lipoprotein uptake may be directed by factors other than LDL receptor density.
Grand Rounds: Nephrotoxicity in a Young Child Exposed to Uranium from Contaminated Well Water
Authors: H. Sonali Magdo, Joel Forman, Nathan Graber, Brooke Newman, Kathryn Klein, Lisa Satlin, Robert W. Amler, Jonathan A. Winston, Philip J. Landrigan
Journal: Environmental Health Perspectives (2007)

ContextPrivate wells that tap groundwater are largely exempt from federal drinking-water regulations, and in most states well water is not subject to much of the mandatory testing required of public water systems. Families that rely on private wells are thus at risk of exposure to a variety of unmeasured contaminants.Case PresentationA family of seven—two adults and five children—residing in rural northwestern Connecticut discovered elevated concentrations of uranium in their drinking water, with levels measured at 866 and 1,160 μg/L, values well above the U.S. Environmental Protection Agency maximum contaminant level for uranium in public water supplies of 30 μg/L. The uranium was of natural origin, and the source of exposure was found to be a 500-foot well that tapped groundwater from the Brookfield Gneiss, a geologic formation known to contain uranium. Other nearby wells also had elevated uranium, arsenic, and radon levels, though concentrations varied widely. At least one 24-hr urine uranium level was elevated (> 1 μg/24 hr) in six of seven family members (range, 1.1–2.5 μg/24 hr). To assess possible renal injury, we measured urinary beta-2-microglobulin. Levels were elevated (> 120 μg/L) in five of seven family members, but after correction for creatine excretion, the beta-2-microglobulin excretion rate remained elevated (> 40 μg/mmol creatinine) only in the youngest child, a 3-year-old with a corrected level of 90 μg/mmol creatinine. Three months after cessation of well water consumption, this child's corrected beta-2-microglobulin level had fallen to 52 μg/mmol creatinine.SignificanceThis case underscores the hazards of consuming groundwater from private wells. It documents the potential for significant residential exposure to naturally occurring uranium in well water. It highlights the special sensitivity of young children to residential environmental exposures, a reflection of the large amount of time they spend in their homes, the developmental immaturity of their kidneys and other organ systems, and the large volume of water they consume relative to body mass.
312. Human Plasminogen Kringle 5-Engineered Murine Mammary Cancer Cells Arrest Tumor Growth and Promote Long-Term Survival
Authors: Sabrina R. Perri, Moïra François, Jacques Galipeau
Journal: Molecular Therapy (2005)

Objective: Neoangiogenesis has been strongly correlated with aggressive breast tumor growth and metastasis. However, since tumor-associated neovasculature is not of malignant origin, it retains the ability to respond physiologically to growth arrest signals and is the proposed basis for breast tumor regression in vivo. The fifth kringle (K5) domain of human plasminogen is distinct from angiostatin (K1-4), and has been shown -on its own- to act as a potent suppressor of angiogenesis. We propose that the K5 domain may serve as a potent angiostatic agent and that it may act as a useful therapeutic transgene within a breast cancer gene therapy strategy. To test this hypothesis, we have developed a K5-expressing retroviral vector, gene-modified murine DA3 mammary cells to produce soluble human K5 protein and characterized the anti-tumor potency of the de novo produced K5 peptide in vivo.
Histopathology of the Skin
Authors: William A. Caro
Journal: JAMA (1976)

The latest edition of this standard textbook has been extensively revised, reflecting the many advances that have occurred in the eight years since the previous edition. Dr Gundula Schaumburg-Lever has become coauthor, and the new edition contains expanded sections on cutaneous biology and electron microscopy. The book has several chapters on basic material, including laboratory methods, embryology, and normal and abnormal histology, histogenesis, and differential diagnosis, arranged systematically for each pathologic condition. The clinical descriptions are concise and informative and have been of great value to the many nondermatologists who use this book. The updated histopathologic descriptions remain lucid and precise, with easily used citations to the pertinent literature. The sections on histogenesis have been expanded considerably and provide the reader a ready entry into investigative areas. Systemic diseases are amply discussed where these have significant cutaneous features. The authors' handling of controversial subjects is well balanced, and they present
Possible Tobramycin Delirium
Authors: J. DeVance Hamilton
Journal: JAMA (1982)

<h3>To the Editor.—</h3> The report inThe Journalof "Possible Tobramycin Delirium" by McCartney and colleagues (1982;247:1319) warrants some comments about attributing their patient's delirium to administration of tobramycin sulfate. First, the patient's age (66 years) is a known predisposing factor for delirium in general, and urinary tract infections alone have been known to cause delirium in elderly patients.<sup>1</sup>Second, from the first day of hospitalization, the patient was given a CNS depressant (flurazepam, 30 mg/day), to which were added (sometime during days 5 to 7) two more CNS depressants (diazepam, 5 to 10 mg/day, and codeine, 30 to 120 mg/day); again, in an elderly patient, this combination per se could easily contribute to or worsen delirium.<sup>2</sup>Third, the disappearance of the delirium within 14 hours after discontinuing tobramycin appears to be remarkably rapid, if tobramycin were indeed the main cause. The time course of the delirium resolution
Effect of A.C.T.H., Cortisone, and D.C.A. with Ascorbic Acid on "Formalin-Arthritis"
Authors: M. W. Parkes, F. Wrigley
Journal: BMJ (1951)

SYMPATHECTOMY FOR HYPERTENSION BicuaJo blood pressure, but that 66% of them have been relieved of incapacitating symptoms and have returned to work.The prognosis for malignant hypertension so far shows a definite improvement as a result of sympathectomy.For a limited but definite group of patients with hypertension, sympathectomy is a valuable procedure.I wish to thank Mr. R. H.
Abstract LB-61: Vemurafenib promotes RAS wild-type tumor formation in a mouse model of HPV-driven cutaneous squamous cell carcinoma.
Authors: Matthew Holderfield, Edward Lorenzana, Ben Weisburd, Lisa Lomovasky, Majid Ghoddusi, Dylan Daniel, Nancy Pryer, Frank McCormick, Darrin Stuart
Journal: Cancer Research (2013)

Abstract A subset of melanoma patients (18-30%) treated with Vemurafenib (and other RAF inhibitors) develop spontaneous cutaneous squamous-cell carcinoma (cSCC) and/or keratoacanthoma (KA). Preclinical studies demonstrate that RAF inhibitors paradoxically activate the MAPK pathway and stimulate growth of RAS mutated cells. Based on these observations it has been proposed that drug induced MAPK activation in pre-cancerous tissues may account for the high incidence of cSCC and KA in treated patients. Because human cSCC is frequently positive for human papillomavirus (HPV) DNA, we hypothesized that RAF inhibitors promote tumorigenesis in HPV infected epidermis. To investigate this possibility, we used a transgenic murine model (K14-HPV16) of cSCC, driven by basal keratinocyte-specific expression (K14 promoter) of HPV type 16 early genes including E6 and E7, which inactivates p53 and pRB tumor suppressors. Exposure to Vemurafenib elevated MAPK markers in epidermis and increased cSCC incidence from 22% to 70%. Exome sequencing revealed that 100% of cSCCs from untreated mice harbored activating RAS mutations, yet 55% of cSCCs from Vemurafenib treated mice were RAS wild-type. Concomitant treatment with a MEK inhibitor reduced cSCC frequency, and MEK inhibitor alone was sufficient to completely regress established cSCCs. Together, these results suggest that cSCC is dependent upon MAPK activation induced either by a RAS oncogene or alternatively by exposure to RAF inhibitors in HPV infected keratinocytes. Citation Format: Matthew Holderfield, Edward Lorenzana, Ben Weisburd, Lisa Lomovasky, Majid Ghoddusi, Dylan Daniel, Nancy Pryer, Frank McCormick, Darrin Stuart. Vemurafenib promotes RAS wild-type tumor formation in a mouse model of HPV-driven cutaneous squamous cell carcinoma. [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 LB-61. doi:10.1158/1538-7445.AM2013-LB-61
Life cycle of toxoplasma gondii.
Authors: W M Hutchison, J F Dunachie, J C Siim, K Work
Journal: BMJ (1969)

cancer discovered by miniature mass radio- graphy.Of course, mass radiography has widened its scope since its introduction in the early1940s.It has become a service, a tool for presymptomatic diagnosis.X-ray depart- ments in hospitals are neither meant nor equipped to do this.To destroy such a service without even taking regional differences and problems into consideration is a retrograde step.-Iam, etc.,
Necessary safeguards when prescribing opioid drugs to addicts: experience of drug dependence clinics in London.
Authors: P H Connell, M Mitcheson
Journal: BMJ (1984)

average factors from standard food tables rather than by direct chemical analysis of the specific items concerned. The same is true, however, for almost all nutritional surveys. (5) As a result of limitations (3) and (4), and because each family takes part in the survey for only seven days, the National Food Survey can say nothing about the nutrient intake or eating behaviour of individual household members or indeed of individual households. It can only reasonably provide estimates for fairly broad groups of households ; but the recommendations of the DHSS are framed in similar terms. Furthermore, the food consumption of any family or individual during a single week, no matter how accurately measured, is unlikely to be directly reflected in their later morbidity or mortality. Epidemio logical studies are therefore usually concerned with group averages. The main strength of the National Food Survey is that it provides continuous information on food and nutrient intakes now spanning more than 30 years, not only for Britain as a whole but also for many subgroups within the population. Though constrained by financial and practical considerations, it remains an up to date, readily accessible, and comparatively cheap means of monitoring trends in household food con? sumption and of assessing a major aspect of nutritional state for epidemiologists to compare with any similar temporal or cross sectional data on morbidity and mortality.
Scientists Discover Proto-Oncogene Role in Normal Development
Authors: P. A. Newman
Journal: JNCI Journal of the National Cancer Institute (1988)

Scientists Discover Proto-Oncogene Role in Normal Development Get access Patricia A. Newman Patricia A. Newman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 19, 7 December 1988, Pages 1515–1516, https://doi.org/10.1093/jnci/80.19.1515 Published: 07 December 1988
Urinary candidiasis after renal transplantation.
Authors: R J Holt, R L Newman
Journal: BMJ (1972)

New Electronic Metal Locator SIR,-We wish to assure Dr. D. Gordon (20 May, p. 467) that we are reasonably familiar with the literature on metal de- tection (most of which appears outside the annals of medicine), and that we have at no time claimed anything other than a new application of modern semiconductor devices and circuit techniques to the problem (15 April, p. 157).The earlier mental locators utilized thermionic valves and so tended to be large and cumbersome.This disad- vantage, along with the tuning difficulties usually associated with the amplitudesensing, two-coil approach, ensured their eventual disappearance.So far as we are aware, there is no medical metal locator on the market at present.-We are, etc.,
Screening With Prostate-Specific Antigen: Should We or Shouldn't We?
Authors: Jerome E. Herbers
Journal: JAMA (1993)

<h3>To the Editor.</h3> —In a recent Editorial<sup>1</sup>Lange reviewed the current evidence for prostate cancer screening. He described the key unresolved issue: whether screening should be done at all in asymptomatic men, given that there is no proof that early diagnosis leads to better health outcomes. I therefore did not understand the basis for his concluding recommendation that "for now the periodic prostate examination should be encouraged" pending the results of ongoing clinical trials. The opposite conclusion seems more appropriate. Sackett and colleagues<sup>2</sup>have described screening for symptom-free individuals in terms of an implicit contract. By this view, we imply a promise to asymptomatic people "not that their subsequent treatment may work but that it does work; not that we will simply do our best, but that they will be better off as a result of the screening program. When we impose ourselves on the public in this
Abstract 3720: Combination treatment with hypoxia-activated prodrug TH-302 and the mTOR inhibitor everolimus results in enhanced antitumor efficacy in preclinical models
Authors: Jessica D. Sun, Dharmendra Ahluwalia, Qian Liu, Yan Wang, Mark D. Matteucci, Charles P. Hart
Journal: Cancer Research (2012)

Abstract TH-302, a 2-nitroimidazole triggered hypoxia-activated prodrug, releases bromo-isophosphoramide mustard (Br-IPM), which induces DNA crosslinking in hypoxic cells. It shows broad antitumor activity in a number of preclinical models, both as a single agent and in combination with conventional chemotherapeutics. The intracellular kinase mTOR plays a key role in multiple pathways which are important in cancer progression. Everolimus directly targets mTOR and results in reduced tumor cell proliferation, decreased tumor angiogenesis, and an inhibiton of tumor cell metabolism. Here we investigated whether TH-302 in combination with everolimus could improve the efficacy profile versus the agents as monotherapies. Two renal cell carcinoma (RCC) ectopic xenograft models and a neuroblastoma ectopic xenograft model were established by subcutaneous implantation of Caki-1, 786-O, or SK-N-BE(2) cells into the flanks of nude mice. When tumor size was approximately 150mm3, animals were treated with everolimus (5mg/kg, QDx19, oral), TH-302 (50mg/kg, QDx5/wk x 3wks, ip), or both everolimus and TH-302. In the Caki-1 model, 87% Tumor Growth Inhibition (TGI) was observed in the combination group versus 52% TGI from everolimus monotherapy or 16% TGI from TH-302 monotherapy. A pharmacodynamic immunohistochemistry study showed that after 7 days of treatment with everolimus, cell proliferation (by Ki67), microvessel density (by CD31) and phosphorylation of the S6 ribosomal protein (by p-S6) was significantly decreased. In the 786-O model, everolimus alone showed 49% TGI, while TH-302 alone did not demonstrate statistically significant efficacy. However, when TH-302 was combined with everolimus, a TGI of 85% was reached. In the ectopic SK-N-BE(2) neuroblastoma model, TH-302 or everolimus alone demonstrated 45% and 40% TGI, respectively, while the combination therapy yielded 65% TGI. Importantly, body weight loss was very minor (&amp;lt;5%) in all groups tested, indicating no significant added toxicity in the combination groups. In summary, there is additive antitumor activity when TH-302 is combined with everolimus. The efficacy profile of TH-302 in combination with the mTOR inhibitor temsirolimus also shows an additive effect in the combination therapy setting. These studies provide a translational rationale for combining TH-302 with mTOR inhibitors to increase the treatment benefit. 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 3720. doi:1538-7445.AM2012-3720