tbuckley/cabot-search huggingface dataset:
Regional nerve blockade prior to direct injection to achieve anaesthesia of the nasal ala
Authors: N.J. Mortimer, W. Hussain, M.J. Sladden, P.J. Salmon
Journal: British Journal of Dermatology (2010)

Journal Article Regional nerve blockade prior to direct injection to achieve anaesthesia of the nasal ala Get access N.J. Mortimer, N.J. Mortimer Dermatologic Surgery Unit, Skin Cancer Institute, 171 Cameron Road, Mount Maunganui, Tauranga, New Zealand Neil J. Mortimer. E‐mail: njmort2002@yahoo.co.uk Search for other works by this author on: Oxford Academic Google Scholar W. Hussain, W. Hussain Dermatologic Surgery Unit, Skin Cancer Institute, 171 Cameron Road, Mount Maunganui, Tauranga, New Zealand Search for other works by this author on: Oxford Academic Google Scholar M.J. Sladden, M.J. Sladden Department of Medicine, University of Tasmania, Launceston, Tasmania, Australia Search for other works by this author on: Oxford Academic Google Scholar P.J. Salmon P.J. Salmon Dermatologic Surgery Unit, Skin Cancer Institute, 171 Cameron Road, Mount Maunganui, Tauranga, New Zealand Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 4, 1 April 2010, Pages 819–821, https://doi.org/10.1111/j.1365-2133.2010.09674.x Published: 01 April 2010
Role of p12CDK2-AP1 in Transforming Growth Factor-β1-Mediated Growth Suppression
Authors: Miaofen G. Hu, Guo-Fu Hu, Yong Kim, Takanori Tsuji, Jim McBride, Philip Hinds, David T. W. Wong
Journal: Cancer Research (2004)

Abstract p12CDK2-AP1 (p12) is a growth suppressor isolated from normal keratinocytes. Ectopic expression of p12 in squamous carcinoma cells reversed the malignant phenotype of these cells, in part due an ability of p12 to bind to both DNA polymerase α/primase and to cyclin-dependent kinase 2 (CDK2), thereby inhibiting their activities. We report in this article that in normal epithelial cells, transforming growth factor β1 (TGF-β1) induces p12 expression transcriptionally, which, in turn, mediates the growth inhibitory activity of TGF-β1. We created inducible p12 antisense HaCaT cell lines [ip12 (−) HaCaT] and showed that selective reduction of cellular p12 resulted in an increase in: (a) CDK2-associated kinase activity; (b) protein retinoblastoma (pRB) phosphorylation; and (c) [3H]thymidine incorporation, and partially reversed TGF-β1-mediated inhibition of CDK2 kinase activity, pRB phosphorylation, and cell proliferation. Furthermore, we generated p12-deficient mouse oral keratinocytes (MOKp12−/−) and compared their growth characteristics and response to TGF-β1 with that of wild-type mouse oral keratinocytes (MOKWT). Under normal culture conditions, the number of MOKp12−/− in S phase is 2-fold greater than that of MOKWT. Concomitantly, fewer cells are in G2 phase in MOKp12−/− than that in MOKWT. Moreover, response to TGF-β1-mediated growth suppression is compromised in MOKp12−/− cells. Mechanistic studies showed that MOKp12−/− have increased CDK2 activity and reduced sensitivity to inhibition by TGF-β1. Collectively our data suggest that p12 plays a role in TGF-β1-mediated growth suppression by modulating CDK2 activities and pRB phosphorylation.
ENTERITIS NECROTICANS AMONG KHMER CHILDREN AT AN EVACUATION SITE IN THAILAND
Authors: Stuart Johnson, David N. Taylor, Rudi Coninx, Boonchuay Eampokalap, Robin A. Cooke, Peter Echeverria, Sakti R. Paul, Jun Sakurai, Prasarn Jimakorn, Gregor W. Lawrence, Peter D. Walker
Journal: The Lancet (1987)
L-tyrosine is a promising cancer vaccine adjuvant
Authors: Hiep Khong, Meenu Sharma, Zhimin Dai, Manisha Singh, Yared Hailemichael, Willem Overwijk
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The choice of adjuvants is critical for any vaccine whether prophylactic or therapeutic. Our group previously showed that incomplete Freund's adjuvant, commonly used in different cancer vaccine trials, had many undesirable effects on T cell trafficking and function which directly
CD20 Expression in Hodgkin and Reed-Sternberg Cells of Classical Hodgkin's Disease: Associations With Presenting Features and Clinical Outcome
Authors: George Z. Rassidakis, L. Jeffrey Medeiros, Simonetta Viviani, Valeria Bonfante, Gian Paolo Nadali, Theodoros P. Vassilakopoulos, Ofelia Mesina, Marco Herling, Maria K. Angelopoulou, Roberto Giardini, Marco Chilosi, Christos Kittas, Peter McLaughlin, M. Alma Rodriguez, Jorge Romaguera, Gianni Bonadonna, Alessandro M. Gianni, Giovanni Pizzolo, Gerassimos A. Pangalis, Fernando Cabanillas, Andreas H. Sarris
Journal: Journal of Clinical Oncology (2002)

PURPOSE: CD20 can be expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin’s disease (HD), but its clinical significance remains controversial. Therefore, we correlated CD20 expression with presenting features and clinical outcome of untreated patients with classical HD. PATIENTS AND METHODS: Patients were eligible if they were previously untreated and human immunodeficiency virus-1 negative, had biopsy-proven classical HD, and if pretreatment paraffin-embedded tumor tissue was available. CD20 expression was determined by immunohistochemistry without knowledge of clinical outcome. A tumor was considered positive if any HRS cells expressed CD20, but other cutoffs for number of CD20-positive HRS were also investigated. RESULTS: We identified 598 patients whose median age was 30 years and of whom 55% were male. HRS cells expressed CD20 in 132 (22%) of 598 patients with classical HD. When any percentage of CD20 expression in HRS cells was used as a cutoff, the 5-year failure-free survival (...
Role for CXCR6 and Its Ligand CXCL16 in the Pathogenesis of T-Cell Alveolitis in Sarcoidosis
Authors: Carlo Agostini, Anna Cabrelle, Fiorella Calabrese, Michela Bortoli, Elisa Scquizzato, Samuela Carraro, Marta Miorin, Bianca Beghè, Livio Trentin, Renato Zambello, Monica Facco, Gianpietro Semenzato
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Receptor expression dictates the spectrum of chemokine actions on immunocompetent cells. We have previously shown that the chemokine receptor CXCR3 is highly expressed by T-helper type 1 (Th1) cells infiltrating the lungs of patients with sarcoidosis.The evaluation of the role of Bonzo/CXCR6 and its ligand CXCL16 in the pathogenesis of sarcoidosis.Immunocompetent cells infiltrating sarcoid lung have been evaluated by flow cytometry, confocal microscopy, immunohistochemical and molecular analysis, and functional assays.Th1 cells isolated from the bronchoalveolar lavage of patients with sarcoidosis and T-cell alveolitis coexpressed CXCR3 and CXCR6. Immunohistochemical analysis of lung specimens has shown that CXCR6+ T cells infiltrated lung interstitium surrounding the central core of the granuloma. The CXCR6 ligand CXCL16 was abundantly expressed by macrophages infiltrating sarcoid tissue and/or forming the granuloma core. From a functional point of view, sarcoid Th1 cells were able to respond to CXCL10 and CXCL16 in migratory assay. In vitro kinetic studies demonstrated that, although CXCR3 was rapidly induced by interleukin (IL)-15 and IL-18, CXCR6 induction was slow (8 d) and mainly regulated by IL-15.T cells coexpressing CXCR3 and CXCR6 act coordinately with respective ligands and Th1 inflammatory cytokines in the alveolitic/granuloma phases of the disease.
Endothelin enhances activity of mechanosensitive channels: A mechanism for ET augmentation of the myogenic response
Authors: H COLEMAN, H PARKINGTON
Journal: Cardiovascular Research (2007)

That stretching smooth muscle can result in contraction has been appreciated for over a hundred years (see [1]), and Bayliss in 1902 [1] demonstrated that an increase in luminal pressure in arteries resulted in passive distension followed by constriction.Neural and hormonal mechanisms were excluded, so mechanisms intrinsic to smooth muscle were invoked to explain this phenomenon, now known as the myogenic response.Reports of stretch-induced activation of depolarization[2] and action potentials [3] in visceral smooth muscle were followed by studies on blood vessels in which increases in luminal pressure were associated with depolarization [4-6] and the initiation of action potentials [4].Attenuation of the myogenic constriction by Ca 2+ channel blockers implicated voltage-operated Ca 2+ channels.But what causes the critical depolarization that activates the Ca 2+ channels?In a wide range of cell types, including vascular smooth muscle [7], negative pressure applied to patch-clamp electrodes activates various ion channels, particularly poorly selective cation channels.Thus, pressurization of blood vessels stretches their walls which activates stretch-sensitive cation channels, resulting in depolarization that activates voltage-operated Ca 2+ channels, and the ensuing influx of Ca 2+ initiates constriction.However, additional dimensions add complexity and raise further questions.These are generally centred on the processes that underlie stretch activation of ion channels, the role of the intracellular and extracellular structural elements (cytoskeleton, integrins, and extracellular matrix (ECM)), and the role and contribution of second messenger pathways.These are all
Preclinical Evaluation of an Anti-Autocrine Growth Factor Monoclonal Antibody for Treatment of Patients With Small-Cell Lung Cancer
Authors: I. L. Avis, T. O. G. Kovacs, P. G. Kasprzyk, A. M. Treston, R. Bartholomew, J. H. Walsh, F. Cuttitta, J. L. Mulshine
Journal: JNCI Journal of the National Cancer Institute (1991)

We have evaluated an anti-autocrine growth factor monoclonal antibody for potential use in the treatment of patients with small-cell lung cancer. The monoclonal antibody, designated 2A11, binds to the C-terminal region of the autocrine growth factor gastrin-releasing peptide and neutralizes its growth-promoting effects in vitro and in vivo. Equilibrium-binding analysis demonstrated that the peptide binds to the antibody (dissociation constant = 1.5 x 10(-10) at least as avidly as it binds to the tumor peptide receptor. Pharmacokinetic studies in normal BALB/c mice demonstrated an initial clearance half-life (alpha t1/2) of 24.3 +/- 4 hours and a secondary clearance half-life (beta t1/2) of 1039.6 +/- 309 hours, and biodistribution studies revealed a distribution pattern which generally reflected blood flow. Single intravenous infusions of 2A11 (20 mg/20-25-kg dogs) into normal mongrel dogs with surgically created gastric fistulas antagonized the stimulatory effects of exogenously infused gastrin-releasing peptide or bombesin on plasma gastrin release and gastric acid secretion. Toxicology studies in normal dogs (with gastric fistulas) infused with 50 mg 2A11 intravenously three times a week for 4 weeks failed to reveal any adverse behavioral, clinical, or pathological effects. Four of six dogs developed an immune response to 2A11. Anti-idiotypic antibodies elicited in two cases did not mimic the functional effects of the peptide. We conclude that the concept of immunoblockade of an autocrine growth factor appears feasible in vivo.
Early detection of renal damage caused by fumaric acid ester therapy by determination of urinary β2-microglobulin
Authors: N. Häring, H. Sprenger Mähr, M. Mündle, R. Strohal, K. Lhotta
Journal: British Journal of Dermatology (2010)

Fumaric acid esters are considered efficacious and safe drugs for the treatment of psoriasis. Renal damage, caused either by acute renal injury or Fanconi syndrome, is a recognized side-effect of this therapy.To investigate whether the measurement of urinary excretion of β2-microglobulin, a marker of renal proximal tubular dysfunction, allows early detection of kidney damage before an increase in serum creatinine or significant proteinuria occurs.Urinary β2-microglobulin excretion was measured regularly in 23 patients undergoing fumaric acid ester therapy.Urinary β2-microglobulin remained normal in all 10 male patients. Three (23%) out of 13 female patients experienced an increase in urinary β2-microglobulin excretion. In two of these patients a sharp increase was observed in association with high doses. One further patient had moderately elevated levels on rather low doses of fumaric acid esters. After discontinuing treatment, urinary β2-microglobulin levels returned to normal within a few weeks.Determination of urinary β2-microglobulin possibly allows early detection of renal damage by fumaric acid esters. Female patients seem to be prone to this side-effect, especially when taking high doses.
Prognostic Factors in Metastatic Rhabdomyosarcomas: Results of a Pooled Analysis From United States and European Cooperative Groups
Authors: Odile Oberlin, Annie Rey, Elizabeth Lyden, Gianni Bisogno, Michael C.G. Stevens, William H. Meyer, Modesto Carli, James R. Anderson
Journal: Journal of Clinical Oncology (2008)

To identify risk factors associated with outcome in children with metastatic rhabdomyosarcoma in a large cohort of patientsPooled data were obtained from 788 patients treated in nine studies performed by European and American cooperative groups. Clinical factors, including age, histology, site of primary, and site(s) and number of sites of metastatic disease, were correlated with event-free survival (EFS) and overall survival (OS).Seven hundred eighty-eight patients were eligible for analysis. The 3-year OS and EFS were 34% (SE, 1.7) and 27% (SE, 1.6), respectively. By univariate analysis, 3-year EFS was significantly and adversely influenced by age, alveolar histology, location of primary tumor in unfavorable site (defined as extremity and "other" sites), presence of three or more sites of metastatic disease, and the presence of bone or bone marrow involvement. By multivariate analysis, EFS was strongly correlated to all factors except histology. Relative risks were 1.6 for age younger than 1 year or at least 10 years, 1.4 for unfavorable site of primary tumor, 1.4 for bone or bone marrow involvement, 1.4 for three or more metastatic sites. EFS was 50% for patients without any of these four adverse factors and was respectively 42%, 18%, 12%, and 5% in patients with one, two, three, or four factors (P < .0001).This analysis identified subsets of patients with metastatic rhabdomyosarcoma with different outcomes to current therapy and offers a strategy to define patient candidates for experimental approaches to treatment.
Antigen acquisition by dendritic cells: intestinal dendritic cells acquire antigen administered orally and can prime naive T cells in vivo.
Authors: L M Liu, G G MacPherson
Journal: The Journal of Experimental Medicine (1993)

In the rat, mesenteric lymphadenectomy allows collection of dendritic cells (DC) derived from the small intestine after cannulation of the thoracic duct. We prepared rats this way and administered antigens by oral feeding or intraintestinal injection. DC enriched from the thoracic duct lymph collected over the first 24 h from these animals are able to stimulate sensitized T cells in vitro and to prime popliteal lymph node CD4+ T cells after footpad injection, while B and T cells from the same thoracic duct lymph are inert in priming. 500 or less DC pulsed in vitro with antigen can prime T cells in vivo, whereas 100 times more B cells or macrophages pulsed in vitro are quite inert. 1 mg of ovalbumin administered orally is sufficient to load DC for in vivo priming of T cells. Antigen could not be detected directly in DC but was present in macrophages in the lamina propria. Direct presentation of antigen by DC to T cells was demonstrated by injecting F1 recipients with parental DC and showing restriction of T cell sensitization to the major histocompatibility complex of the injected DC. Antigen-bearing DC do not induce a detectable primary antibody response but a small secondary antibody response can be detected after a boosting injection. These results show that acquisition of antigens by DC in the intestine is very similar to what occurs in vitro or in other tissues, suggesting that there may be no special difference in antigen handling at mucosal surfaces. One implication of these results is that hypotheses designed to explain oral tolerance must take into account the presence of immunostimulatory, antigen-bearing DC in animals that have received oral antigens.
Pancreas-specific RelA/p65 truncation increases susceptibility of acini to inflammation-associated cell death following cerulein pancreatitis
Authors: Hana Algül, Matthias Treiber, Marina Lesina, Hassan Nakhai, Dieter Saur, Fabian Geisler, Alexander Pfeifer, Stephan Paxian, Roland M. Schmid
Journal: Journal of Clinical Investigation (2007)

Activation of the transcription factor NF-kappaB/Rel has been shown to be involved in inflammatory disease. Here we studied the role of RelA/p65, the main transactivating subunit, during acute pancreatitis using a Cre-loxP strategy. Selective truncation of the rela gene in pancreatic exocrine cells led to both severe injury of the acinar cells and systemic complications including lung and liver damage. Our data demonstrated that expression and induction of the protective pancreas-specific acute phase protein pancreatitis-associated protein 1 (PAP1) depended on RelA/p65. Lentiviral gene transfer of PAP1 cDNA reduced the extent of necrosis and infiltration in the pancreata of mice with selective truncation of RelA/p65. These results provide in vivo evidence for RelA/p65 protection of acinar cell death via upregulation of PAP1. Moreover, our data underscore the pancreas-specific role of NF-kappaB/Rel and suggest multidimensional roles of NF-kappaB/Rel in different cells and contexts during inflammation.
Pancreatic Stellate Cells and Pancreatic Cancer Cells: An Unholy Alliance
Authors: Alain Vonlaufen, Phoebe A. Phillips, Zhihong Xu, David Goldstein, Romano C. Pirola, Jeremy S. Wilson, Minoti V. Apte
Journal: Cancer Research (2008)

Pancreatic cancer--a tumor displaying a particularly abundant stromal reaction--is notorious for its poor prognosis. Recent studies, via newly developed orthotopic models, provide compelling evidence of an important role for pancreatic stellate cells (PSC) in pancreatic cancer progression. Characterization of the mechanisms mediating PSC-cancer interactions will lead to the development of much needed alternative therapeutic approaches to improve disease outcome.
Potential Pitfalls of Crossover and Thoughts on Iniparib in Triple-Negative Breast Cancer
Authors: T. Fojo, L. Amiri-Kordestani, S. E. Bates
Journal: JNCI Journal of the National Cancer Institute (2011)

As recruitment for oncology clinical trials has become more difficult, there appears to have been an increase in the number of studies that allow patients in the control arm to "crossover" and receive the experimental therapy after disease progression. Although some researchers worry that allowing such crossover may abolish gains in progression-free survival in the experimental arm, the possibility that crossover might inadvertently benefit the experimental arm has not been addressed. In clinical trials in which the experimental agent has little or no intrinsic activity and is used to modulate an active combination, such crossover might negatively affect the overall survival of the control arm. Because resistance to the active combination—manifested as disease progression—has occurred, the likelihood of benefit from adding the experimental drug is reduced. Consequently, patients who were randomly assigned to the control arm continue to receive the now inactive combination after crossover, whereas patients in the experimental arm who discontinue study participation may seek out potentially effective salvage regimens. This difference in subsequent therapies may confer an advantage to the experimental arm that is manifested as gains beyond those achieved in progression-free survival, gains that occur not because the experimental therapy induced a change in tumor biology that persists beyond treatment discontinuation but because the control arm suffers by continuing to receive a therapy on which their tumor is progressing. Such an outcome may explain the recently reported trial results for iniparib in triple-negative breast cancer. Given that allowing patients in the control arm to receive the experimental agent may confound interpretation of overall survival, such crossover should not be used indiscriminately, especially if the experimental agent has little or no intrinsic activity.
THE EFFECT OF HYPERGLYCEMIA ON HYPOTHALAMIC GOLD UPTAKE AND HYPERPHAGIA IN GOLDTHIOGLUCOSE-TREATED MICE
Authors: P. Michael Edelman, Irving L. Schwartz, Eugene P. Cronkite, George Brecher, Linda Livingston
Journal: The Journal of Experimental Medicine (1965)

The accumulation of gold in the hypothalamus and the development of hyperphagia and obesity were studied in mice given a single intravenous injection of goldthioglucose at various levels of blood glucose concentration. It was found that the glucose concentration prevailing at the time of goldthioglucose injection was correlated directly with the level of free and bound goldthioglucose in the blood 3 minutes later, with the hypothalamic uptake of gold, with the extent of the hypothalamic lesion, and with the severity of the subsequent hyperphagia and obesity. Hyperglycemia was associated with an increased gold deposition throughout the brain. A gold content of 88 +/- 12 microg/mg wet tissue in the hypothalamus of fasted animals was associated with clearcut lesions in all animals studied, whereas a similar gold content in the control brain lobes of hyperglycemic animals was not associated with lesions in any animal. This finding indicates that some regions in the brain (e.g. the ventral hypothalamus) are more susceptible than others to damage by goldthioglucose.
Bronchial Responsiveness to Adenosine 5 ′ -Monophosphate (AMP) and Methacholine Differ in Their Relationship with Airway Allergy and Baseline FEV<sub>1</sub>
Authors: GEA DE MEER, DICK HEEDERIK, DIRKJE S. POSTMA
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Bronchial hyperresponsiveness (BHR) and inflammation are central hallmarks of asthma. Studies in patients with asthma suggest that BHR to adenosine 5 ′ -monophosphate (AMP) is a better marker of bronchial inflammation than BHR to methacholine. The association between markers of airway inflammation and BHR to methacholine and AMP in a population of young adults, with mild symptoms if any, was evaluated. A total of 230 subjects who participated in a follow-up study on occupational allergy were included. Before exposure to occupational allergens, subjects completed a questionnaire on respiratory symptoms and were tested for atopy, blood eosinophilia ( ⩾ 275/mm3), and BHR to methacholine and AMP ( ⩾ 15% fall in FEV1). Risk estimates were expressed as prevalence ratios (PR) and 95% confidence intervals (95% CI). Dose– response slopes (DRS) for methacholine and AMP were compared between healthy control subjects, self-reported allergic rhinitis, and allergic asthma. BHR to AMP was associated with allergic rhinitis (PR 2.51, 95% CI: 1.22;5.17), allergic asthma (PR 4.38, 95% CI: 1.98;9.66), with atopy (PR 3.87, 95% CI: 1.76;8.52), and blood eosinophilia (PR 3.57, 95% CI: 1.48;8.77), but not with baseline FEV1. BHR to methacholine was inversely related to prechallenge FEV1 (PR 0.97, 95% CI: 0.96;0.99). For both methacholine and AMP the geometric mean DRS increased along the axis asymptomatic–allergic rhinitis–allergic asthma, but for AMP the increase was the strongest. In this population study among young adults, BHR to AMP refers to allergic background of airway lability and BHR to methacholine is related to a diminished airway caliber.