tbuckley/cabot-search huggingface dataset:
Polo-like kinase 1: a new target for the management of skin cancers
Authors: Travis Schmit, Minakshi Nihal, Nihal Ahmad
Journal: Cancer Research (2007)

5410  Skin cancer, the most common cancer world wide, encompasses several different types of cancer including the less invasive basal cell carcinoma squamous cell carcinoma as well as malignant melanoma. More than one million new cases of non-melanoma skin cancers are diagnosed annually in the United States. Further, it is estimated that melanoma will account for about 62,190 new cases and most (about 7,910) of the 10,710 skin-cancer related deaths this year. Because the existing preventive or treatment approaches have not been able to effectively manage skin cancers, novel mechanism and target-based approaches are needed. A clear understanding of genetic controls of cellular proliferation and cell division may provide the basis for the rational design of specific targets and therapeutic strategies for the management of skin cancer. Polo-like kinases (Plk) are the family of mitotic serine/threonine kinases, which are highly conserved among eukaryotes and have been shown to play critical role in cell cycle progression, especially during cell division. Plk1, the most well-studied member of this family has many functions in controlling cell cycle progression. These include centrosome maturation, bipolar spindle formation, activation of Cdk1/Cyclin B1 cascade promoting entry into mitosis and finally regulation of anaphase promoting complex (APC) targeted degradation which is necessary for mitotic exit. Elevated Plk1 expression has been shown in many human cancers and is believed to be an indicator of poor prognosis and disease outcome suggesting its possible role as an oncogene. Here, employing many skin cancer cell lines viz. human squamous cell carcinoma A253 cells, human metastatic melanoma Hs-294T cells, and human epidermoid carcinoma A431 cells, normal human epidermal keratinocytes (NHEK) and human tissue arrays containing a variety of skin tumors and normal skin samples, we determined the expression of Plk1 in skin cancers versus normal tissues. Our data from immunoblot- as well as quantitative real time PCR- analyses demonstrated that Plk1 is significantly overexpressed in A253, Hs-294T and A431 cells compared to the NHEKs. Further, this increase in Plk1 was found to be accompanied with an increased expression in the protein levels of Cdc25C, Cdk1 and CyclinB1. Furthermore, our preliminary results of immunohistochemical analyses demonstrated that Plk1 expression is markedly upregulated in a wide range of skin tumors compared to the non-cancerous skin. Thus, our data suggest that Plk1 could be a potential target for designing novel strategies for the prevention and treatment of skin cancer. However, further mechanistic studies are needed to support and confirm this suggestion.
Degradation of eschar from venous leg ulcers using a recombinant chymotrypsin from <i>Lucilia sericata</i>
Authors: G. Telford, A.P. Brown, R.A.M. Seabra, A.J. Horobin, A. Rich, J.S.C. English, D.I. Pritchard
Journal: British Journal of Dermatology (2010)

Journal Article Degradation of eschar from venous leg ulcers using a recombinant chymotrypsin from Lucilia sericata Get access G. Telford, G. Telford Immune Modulation Research Group, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.P. Brown, A.P. Brown Immune Modulation Research Group, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.A.M. Seabra, R.A.M. Seabra Immune Modulation Research Group, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.J. Horobin, A.J. Horobin Immune Modulation Research Group, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. Rich, A. Rich Department of Dermatology, Queen's Medical Centre, University Hospital, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.S.C. English, J.S.C. English Department of Dermatology, Queen's Medical Centre, University Hospital, Nottingham NG7 2UH, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.I. Pritchard D.I. Pritchard Immune Modulation Research Group, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K. David I. Pritchard. E‐mail: david.pritchard@nottingham.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 3, 1 September 2010, Pages 523–531, https://doi.org/10.1111/j.1365-2133.2010.09854.x Published: 01 September 2010
Associations of efficacy outcomes following bronchoscopic thermal vapor ablation (BTVA) for the treatment of heterogeneous emphysema
Authors: Peter Hopkins, Felix J.F. Herth, Gregory Snell, Kim Baker, Christian Witt, Mark H. Gotfried, Arschang Valipour, Manfred Wagner, Franz Stanzel, Jim Egan, Steven Kesten, Armin Ernst
Journal: European Respiratory Journal (2011)

Background:  The associations among various COPD efficacy endpoints are variable; however, the degree of correlation is often important in examining the consistency of the results across measures that are not considered redundant.   Objectives:  Determine the correlations of improvements in lung function and CT analysis of lobar volume reduction (LoVR) to health outcomes following treatment of heterogeneous emphysema with BTVA.   Methods:  Single-arm trial of BTVA in patients with upper lobe predominant emphysema. Patient criteria: FEV 1  15% - 45% predicted, age 40-75 years, RV>150%, TLC>100%, 6 minute walk distance (6MWD)>140 m, DLCO>20%, previous pulmonary rehabilitation. Primary efficacy endpoints: FEV 1  and St. George9s Respiratory Questionnaire total score (SGRQ) at 6 months. Other endpoints: body plethysmography, mMRC dyspnea, 6MWD. Pearson correlation coefficients were calculated for the association of changes from baseline to 6 months of physiologic measures and LoVR to health outcomes.   Results:  44 patients received BTVA. Mean age: 63 years, men 50%, FEV 1  0.86 (31% predicted), RV 237% predicted, DLCO 35% predicted, SGRQ 59 units, 6MWD 300 m, mMRC 2.9.   Conclusion:  Physiologic and CT LoVR outcomes correlate strongest with the BODE score and the perception of dyspnea. The variable degree of correlation among the health outcomes indicates the need to examine multiple efficacy variables in emphysema and reinforce that the measures are not redundant.
Grass Pollen Hyposensitization versus Placebo Therapy
Authors: A. Weyer, N. Donat, C. L'Heritier, F. Juilliard, G. Pauli, B. Soufflet, B. David
Journal: Allergy (1981)

The present work reports the results of a double‐blind clinical trial, comparing the effects of hyposensitization treatment versus placebo in 33 patients with allergic rhinitis, sensitive to a crude extract of the pollen of four different grasses (Dactylis glamerata, Lolium perenne, Secale cereale , and Phlewn pratense). The distribution of these patients in the two groups was done randomly and gave two comparable groups, as far as clinical and biological features are concerned. The treatment course included five low doses of the aqueous extract followed by 12 injections of Al(OH) 3 ‐adsorbed aliquots of the same extract. Evaluation of the clinical scores was based on diary cards on which symptoms and medications were recorded. A reevaluation of the significance of the symptom and medication scores is presented and the link between both scores is studied. Particular attention is given to the methodological and statistical problems raised during this study. The non‐parametric tests reveal a significant difference ( P &lt; 0.03) in the total clinical score between the treated and the placebo groups for the second half of the observation period, when the pathology was most intense.
The BH3‐only protein BID impairs the p38‐mediated stress response and promotes hepatocarcinogenesis during chronic liver injury in mice
Authors: Johanna Orlik, Sven Schüngel, Laura Elisa Buitrago‐Molina, Silke Marhenke, Robert Geffers, Jessica Endig, Katharina Lobschat, Stephanie Rössler, Benjamin Goeppert, Michael P. Manns, Atan Gross, Arndt Vogel
Journal: Hepatology (2015)

Apoptosis is critical for maintaining tissue homeostasis, and apoptosis evasion is considered as a hallmark of cancer. However, increasing evidence also suggests that proapoptotic molecules can contribute to the development of cancer, including liver cancer. The aim of this study was to further clarify the role of the proapoptotic B‐cell lymphoma 2 homology domain 3 (BH3)‐only protein BH3 interacting‐domain death agonist (BID) for chronic liver injury (CLI) and hepatocarcinogenesis (HCG). Loss of BID significantly delayed tumor development in two mouse models of Fah ‐mediated and HBsTg ‐driven HCG, suggesting a tumor‐promoting effect of BID. Liver injury as well as basal and mitogen‐stimulated hepatocyte proliferation were not modulated by BID. Moreover, there was no in vivo or in vitro evidence that BID was involved in DNA damage response in hepatocytes and hepatoma cells. Our data revealed that CLI was associated with strong activation of oxidative stress (OS) response and that BID impaired full activation of p38 after OS. Conclusion: We provide evidence that the tumor‐promoting function of BID in CLI is not related to enhanced proliferation or an impaired DNA damage response. In contrast, BID suppresses p38 activity and facilitates malignant transformation of hepatocytes. (H epatology 2015;62:816–828)
A "heartlift" patient
Authors: J. Hollis-Triantafillou
Journal: BMJ (1995)

There's a new disease around, and I miss Louella who, in a long line of enthralling, infuriating, challenging patients, undoubtedly holds pride of place. I first met her in 1983 and our association lasted seven years; officially she was my patient, but in terms of “learning experiences,” as she would have put it, I think I gained more than she did.

In her mid-30s, she was an American writer who had lived many years in Greece. Her first visit to me was unremarkable--a vague history of recurrent sore throats, tiredness, and general aches and pains with no physical signs. I raised the possibility of glandular fever and suggested some blood tests, which were inconclusive. …
Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2
Authors: Andrew Escayg, Bryan T. MacDonald, Miriam H. Meisler, Stéphanie Baulac, Gilles Huberfeld, Isabelle An-Gourfinkel, Alexis Brice, Eric LeGuern, Bruno Moulard, Denys Chaigne, Catherine Buresi, Alain Malafosse
Journal: Nature Genetics (2000)
Task force 6: Code of conduct for staff and volunteer leadership
Authors: Pamela S. Douglas, Thomas J. Ryan, George A. Beller, Edward F. Hines, David Wm Livingston, Christine W. McEntee, Nancy A. Brown, Karen J. Collishaw, Arthur Garson, Rose Marie Robertson, Sidney C. Smith, Gayle R. Whitman
Journal: Journal of the American College of Cardiology (2004)
Abstract 16271: Transmural Dispersion of Myocardial Contraction in Patients With Long QT Syndrome 2 and Jervell and Lange-Nielsen Syndrome
Authors: Kristina H Haugaa, Jan P Amlie, Knut-Erik Berge, Trond P Leren, Otto A Smiseth, Thor Edvardsen
Journal: Circulation (2010)

Introduction: LQTS is characterized by prolonged myocardial action potential duration (APD). The longest APD is reported in the endo- and mid-myocardium. Prolonged APD in LQTS may cause prolonged c...
Abstract 866: Identification of novel early detection candidate protein biomarkers for ER+/PR+ invasive ductal breast carcinoma using pre-clinical plasma from the Women's Health Initiative Observational Study
Authors: Matthew F. Buas, Yuzheng Zhang, Junghyun Rho, Margaret Pepe, Paul Lampe, Christopher Li
Journal: Cancer Research (2014)

Abstract Estrogen receptor (ER)-positive/progesterone receptor (PR)-positive invasive ductal carcinoma accounts for approximately 45% of all invasive breast cancers (BC) diagnosed in the United States each year. While mammography screening and adjuvant hormonal therapy have played key roles in reducing breast cancer mortality, an important challenge remains the development of clinically useful blood-based biomarkers for early detection. The objective of this study was to identify and initially validate novel candidate markers for ER+/PR+ ductal BC, using pre-clinical plasma samples collected up to 12.5 months before diagnosis from 121 cases, 121 matched controls, and 201 non-matched controls from the Women's Health Initiative Observational Study. These specimens were equally divided into training and testing sets and interrogated by a customized antibody array, which included over 3,000 antibodies targeting more than 2,000 proteins. In the training set, statistically significant differences in matched case versus control signals were observed for 374 (11.4 %) antibodies at P&amp;lt;0.05, with 42 of these 374 candidates confirmed in the testing set (P&amp;lt;0.05). Four markers remained significant in the pooled matched pairs sample set after Bonferroni correction for multiple comparisons (P&amp;lt;0.05/3286=1.52x10-5). Areas under the curve for the full list of candidates ranged from 0.55 to 0.66, when assessed in an expanded sample including non-matched controls. With specificity set at 95%, sensitivity ranged from 4 to 19%, with six candidates having a sensitivity of ≥15% at 95% specificity and ≥20% at 90% specificity. The majority of these putative markers did not overlap with those identified in a parallel analysis of triple-negative BC from the same cohort population, suggesting the potential for BC sub-type specificity at the level of the pre-clinical plasma proteome. Additional studies are needed to validate these findings in larger sample sets and further explore their biologic implications in relation to ER+/PR+ BC etiology. Citation Format: Matthew F. Buas, Yuzheng Zhang, Junghyun Rho, Margaret Pepe, Paul Lampe, Christopher Li. Identification of novel early detection candidate protein biomarkers for ER+/PR+ invasive ductal breast carcinoma using pre-clinical plasma from the Women's Health Initiative Observational Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 866. doi:10.1158/1538-7445.AM2014-866
The effect of long-term treatment with tacalcitol on the psoriatic epidermis. A flow cytometric analysis
Authors: None Mommers, None Castelijns, None Seegers, None Van Rossum, None Van Hooijdonk, None Van Erp, None Van DE Kerkhof
Journal: British Journal of Dermatology (1998)

During the last decade, novel analogues of 1α,25-dihydroxy vitamin D3 have been developed for the treatment of psoriasis. Recently, the efficacy of short-term treatment with the novel derivative tacalcitol (1α,24-dihydroxy vitamin D3) has been documented. However, data on the long-term effect of tacalcitol on psoriatic skin are sparse. In this study, we assessed the cell characteristics of the psoriatic epidermis after treatment with tacalcitol for up to 24 weeks. We investigated how long-term treatment with tacalcitol modulates the percentages of differentiated keratinocytes, inflammation cells and basal keratinocytes, and the percentage of cells in the SG2M phase in the basal cell population. From 11 patients who were treated with tacalcitol for up to 18 months, we obtained single-cell suspensions of a representative psoriatic lesion after 0, 8, 12, 18 and 24 weeks of treatment. A Psoriasis Area and Severity Index was performed at each visit as well. Cell suspensions were stained with markers for inflammation (Vim3B4), differentiation (RKSE60) and proliferation (TO-PRO-3 iodide) and analysed flow cytometrically. Clinically, patients improved significantly after 8 weeks of treatment. This clinical effect was preserved for the rest of the period of treatment with no further significant improvement. Proliferative activity also decreased significantly after 8 weeks of treatment. Proliferation did not show further significant decreases or habituation after 12, 18 and 24 weeks. For inflammation, no statistically reliable trends could be seen. Differentiation improved significantly after 8 weeks of treatment, but decreased again significantly after 12 weeks. In the period from 12 to 24 weeks, no further significant change was observed. We conclude that tacalcitol is an effective antipsoriatic drug. Prolonged treatment with tacalcitol will generally maintain improvement at the level reached after 8 weeks. Owing to the beneficial effect on both clinical state and proliferation, tacalcitol is likely to be an adequate maintenance therapy.
Treating the Developing versus Developed Brain: Translating Preclinical Mouse and Human Studies
Authors: B.J. Casey, Charles E. Glatt, Francis S. Lee
Journal: Neuron (2015)

Behaviors and underlying brain circuits show characteristic changes across the lifespan that produce sensitive windows of vulnerability and resilience to psychopathology. Understanding the developmental course of these changes may inform which treatments are best at what ages. Focusing on behavioral domains and neurobiological substrates conserved from mouse to human supports reciprocal hypothesis generation and testing that leverages the strengths of each system in understanding their development. Introducing human genetic variants into mice can further define effects of individual variation on normative development, how they contribute to risk and resilience for mental illness, and inform personalized treatment opportunities. This article emphasizes the period of adolescence, when there is a peak in the emergence of mental illness, anxiety disorders in particular. We present cross-species studies relating fear learning to anxiety across development and discuss how clinical treatments can be optimized for individuals and targeted to the biological states of the developing brain.
Cutaneous neonatal lupus erythematosus in four siblings
Authors: P. Monari, G. Gualdi, F. Fantini, A. Giannetti
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Neonatal lupus erythematosus (NLE) is a form of lupus erythematosus (LE) first described in 1954,1 representing a model of passive autoimmune disease in which pathogenetic autoantibodies are transmitted from mother to foetus through the placenta. Maternal autoantibodies are generally anti‐Ro/SSA or anti‐La/SSB, less frequently anti‐U1RNP. NLE is characterized by a combination of dermatological, cardiac, haematological and hepatic manifestations. Cutaneous lesions consist of erythematous papules and annular discoid or polycyclic plaques, with or without fine scales. They can occur on sun‐exposed areas, often with a typical periorbital distribution. Skin lesions can occur either at birth or, more often, within a few weeks after birth. They are transient and disappear along with autoantibody levels in 6–9 months, sometimes leaving permanent marks. Cardiac involvement occurs mainly with conduction defects and congenital heart block (CHB). Haematological abnormalities (haemolytic anaemia, neutropenia and thrombocytopenia) and hepatic involvement (abnormalities of liver function tests) are often asymptomatic and transient. Mothers may be affected by systemic LE, Sjögren syndrome or other autoimmune diseases, or may be clinically asymptomatic at the time of birth. We report four siblings, born to a woman affected by serological LE, who presented only the cutaneous form of NLE.
Impact of the 2009 influenza A(H1N1) pandemic on public health workers in the Netherlands
Authors: L Vinck, L Isken, M Hooiveld, M C Trompenaars, J IJzermans, A Timen
Journal: Eurosurveillance (2011)

A cross-sectional study was undertaken to analyse the impact of the 2009 influenza A(H1N1) pandemic on frontline public health workers in the Netherlands and to consider its implications for future pandemics. A structured, self-administered questionnaire was made available online (26 March to 26 May 2010) for frontline public health workers employed by the communicable disease departments of the public health services in the Netherlands (n=302). A total of 166 questionnaires (55%) were completed. The majority of respondents reported an increased workload, perceived as too busy (117 respondents, 70.5%) or extreme (13 respondents, 7.8%). Most respondents were not anxious about becoming infected (only seven were regularly concerned). The overall compliance with the control measures was good. The case definition was strictly applied by 110 of the 166 respondents (66%); 56 of 141 (39.7%) consistently consulted the Preparedness and Response Unit within a centralised assessment system, while 68 of 141 (48.2%) consulted the unit only at the beginning of the pandemic. Of 145 respondents with available data, 128 (88.3%) always used personal protective equipment. Reported adherence to the advice to discuss the various isolation measures with patients and their contacts was between 71% and 98.7%. Our study shows that the surveyed frontline public health workers considered the workload to be high during the first 3.5 months of the pandemic and their level of anxiety about becoming infected was reported to be low. During the pandemic, these workers were able to accommodate what they considered to be an excessive workload, even though initially their assignments were unfamiliar to them.
Localized scleroderma-like lesions after bone marrow transplantation in man.
Authors: W.A. VLOTEN, E. SCHEFFER, L.J. DOOREN
Journal: British Journal of Dermatology (1977)

Localized scleroderma-like skin lesions which developed in two children, from 8 to 10 months after successful bone marrow transplantation for aplastic anaemia, showed histopathological features resembling those of scleroderma. This finding, like the animal models described in the literature, provides additional support for the auto-immune nature of scleroderma.
Searching for Joy in Residency by Listening to Our Patients
Authors: Blake Charlton, Rachel J. Stern
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal