tbuckley/cabot-search huggingface dataset:
Peripheral anchorage of dermal equivalents
Authors: C.A.LOPEZ VALLE, F.A. AUGER, P. ROMPRE, VERONIQUE BOUVARD, LUCIE GERMAIN
Journal: British Journal of Dermatology (1992)

Journal Article Peripheral anchorage of dermal equivalents Get access C.A.LÓPEZ VALLE, C.A.LÓPEZ VALLE Department of Microbiology, Laval University, Sainte‐Foy Quebec, Canada, G1K 7P4Skin Culture Laboratory, Saint‐Sacrement Hospital, Quebec, Quebec, Canada, G1S 4L8 Search for other works by this author on: Oxford Academic Google Scholar F.A. AUGER, F.A. AUGER Skin Culture Laboratory, Saint‐Sacrement Hospital, Quebec, Quebec, Canada, G1S 4L8Department of Surgery, Laval University, Sainte‐Foy, Quebec, Canada. G1K 7P4 Dr F.Auger, Laboratoire de recherche des grands brûlés, Hôpital du Saint‐Sacrement, 1050 chemin Sainte‐Foy, Québec, Canada, G1S 4L8. Search for other works by this author on: Oxford Academic Google Scholar P. ROMPRÉ, P. ROMPRÉ Skin Culture Laboratory, Saint‐Sacrement Hospital, Quebec, Quebec, Canada, G1S 4L8Department of Chemical Engineering, Laval University, Sainte‐Foy, Quebec, Canada, G1K 7P4 Search for other works by this author on: Oxford Academic Google Scholar VÉRONIQUE BOUVARD, VÉRONIQUE BOUVARD Skin Culture Laboratory, Saint‐Sacrement Hospital, Quebec, Quebec, Canada, G1S 4L8 Search for other works by this author on: Oxford Academic Google Scholar LUCIE GERMAIN LUCIE GERMAIN Skin Culture Laboratory, Saint‐Sacrement Hospital, Quebec, Quebec, Canada, G1S 4L8Department of Surgery, Laval University, Sainte‐Foy, Quebec, Canada. G1K 7P4 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 4, 1 October 1992, Pages 365–371, https://doi.org/10.1111/j.1365-2133.1992.tb00455.x Published: 01 October 1992
Calcium Kidney Stones
Authors: Elaine M. Worcester, Fredric L. Coe
Journal: New England Journal of Medicine (2010)

A 43-year-old man presents for evaluation of recurrent kidney stones. He passed his first stone 9 years earlier and has had two additional symptomatic stones. Analysis of two stones showed that they contained 80% calcium oxalate and 20% calcium phosphate. The urinary volume was 1.54 liters per day, and the urine pH was 5.6. The patient had been treated with 20 to 40 mmol of potassium citrate daily since he passed his first stone. How should he be further evaluated and treated?
B<scp>REATHING</scp>: Rhythmicity, Plasticity, Chemosensitivity
Authors: Jack L. Feldman, Gordon S. Mitchell, Eugene E. Nattie
Journal: Annual Review of Neuroscience (2003)

Breathing is a vital behavior that is particularly amenable to experimental investigation. We review recent progress on three problems of broad interest. (i) Where and how is respiratory rhythm generated? The preBötzinger Complex is a critical site, whereas pacemaker neurons may not be essential. The possibility that coupled oscillators are involved is considered. (ii) What are the mechanisms that underlie the plasticity necessary for adaptive changes in breathing? Serotonin-dependent long-term facilitation following intermittent hypoxia is an important example of such plasticity, and a model that can account for this adaptive behavior is discussed. (iii) Where and how are the regulated variables CO2 and pH sensed? These sensors are essential if breathing is to be appropriate for metabolism. Neurons with appropriate chemosensitivity are spread throughout the brainstem; their individual properties and collective role are just beginning to be understood.
Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea
Authors: A. P Abernethy
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To determine the efficacy of oral morphine in relieving the sensation of breathlessness in patients in whom the underlying aetiology is maximally treated. <b>Design</b> Randomised, double blind, placebo controlled crossover study. <b>Setting</b> Four outpatient clinics at a hospital in South Australia. <b>Participants</b> 48 participants who had not previously been treated with opioids (mean age 76, SD 5) with predominantly chronic obstructive pulmonary disease (42, 88%) were randomised to four days of 20 mg oral morphine with sustained release followed by four days of identically formulated placebo, or vice versa. Laxatives were provided as needed. <b>Main outcome measures</b> Dyspnoea in the morning and evening as shown on a 100 mm visual analogue scale, quality of sleep, wellbeing, performance on physical exertion, and side effects as measured at the end of the four day treatment period. <b>Results</b> 38 participants completed the study; three withdrew because of definite and two because of possible side effects of morphine (nausea, vomiting, and sedation). Participants reported significantly different dyspnoea scores when treated with morphine: an improvement of 6.6 mm (95% confidence interval 1.6 mm to 11.6 mm) in the morning and of 9.5 mm (3.0 mm to 16.1 mm) in the evening (P = 0.011 and P = 0.006, respectively). During the period in which they were taking morphine participants also reported better sleep (P = 0.039). More participants reported distressing constipation while taking morphine (9 <i>v</i> 1, P = 0.021) in spite of using laxatives. All other side effects were not significantly worse with morphine, although the study was not powered to address side effects. <b>Conclusions</b> Sustained release, oral morphine at low dosage provides significant symptomatic improvement in refractory dyspnoea in the community setting.
GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers
Authors: Craig H Mermel, Steven E Schumacher, Barbara Hill, Matthew L Meyerson, Rameen Beroukhim, Gad Getz
Journal: Genome biology (2011)

We describe methods with enhanced power and specificity to identify genes targeted by somatic copy-number alterations (SCNAs) that drive cancer growth. By separating SCNA profiles into underlying arm-level and focal alterations, we improve the estimation of background rates for each category. We additionally describe a probabilistic method for defining the boundaries of selected-for SCNA regions with user-defined confidence. Here we detail this revised computational approach, GISTIC2.0, and validate its performance in real and simulated datasets.
Stigma and Addiction: Being and Becoming
Authors: Daniel Buchman, Peter B. Reiner
Journal: The American Journal of Bioethics (2009)

In his account of clinical neuroscience and subjectivity, Gillett (2009) provides three examples of neurological conditions that dramatically affect the lived experience of the individual: locked in syndrome, persistent vegetative state, and minimally conscious state. Yet for individuals with mental illnesses such as severe addiction, embodied subjectivity may have different implications for human identity. Because attitudes towards individuals with addiction are heavily moralized, being somebody somewhere with an addiction may result in both self- and other-labeling, and consequently, a development of a “spoiled” public identity.

Our response will briefly focus on the potential implications of neuroscience and human subjectivity in addiction. Using the so-called “brain disease” model of addiction as an illustrative example, we argue that the development of a stigmatizing identity of an ‘addict’ is gradual, and emerges through a complex process which includes, but is not limited to, the individual’s narrative history, social lived experience, neuro-genetics, and a self-labeling process. Since identity emerges from, in part, and is preserved through relationships, a stigmatizing illness identity considerably affects the being-in-the-world-with-others for “the addict”.
Antitumor effects of pharmacological EZH2 inhibition on malignant peripheral nerve sheath tumor through the miR-30a and KPNB1 pathway
Authors: Pingyu Zhang, Xianbin Yang, Xiaoyan Ma, Davis R Ingram, Alexander J Lazar, Keila E Torres, Raphael E Pollock
Journal: Molecular Cancer (2015)

Enhancer of zeste homolog 2 (EZH2) is a key epigenetic regulator in cancer cell survival, epithelial-mesenchymal transition, and tumorigenesis. Inhibition of EZH2 has become a promising therapeutic option for various human malignancies. Previously, we demonstrated that the EZH2/miR-30d/karyopherin (importin) beta 1 (KPNB1) signaling pathway is critical for malignant peripheral nerve sheath tumor (MPNST) cell survival in vitro and for tumorigenesis in vivo. Here, we sought to determine the antitumor effects of pharmacological inhibition of EZH2 on MPNST in vitro and in vivo. We investigated the effects of an EZH2 inhibitor, 3-deazaneplanocin A (DZNep), on MPNST cell cycle, survival and apoptosis in vitro and on MPNST xenograft tumor growth in vivo. We found that DZNep treatment impaired MPNST cell viability and proliferation by inducing apoptosis and cell cycle arrest in vitro. Consistently, DZNep treatment also reduced EZH2 and KPNB1 protein levels and upregulated miR-30d expression in MPNST cells. Intraperitoneal administration of DZNep significantly suppressed MPNST tumor initiation and growth rates in a MPNST xenograft mouse model. Immunoblot and immunohistochemical analyses showed that DZNep downregulated EZH2/KPNB1 signaling in vivo, thereby inhibiting MPNST tumor cell proliferation, and induced cell death. We also found that EZH2 inhibited expression of another miR-30 family member, miR-30a, in MPNST cells. Similar to miR-30d, miR-30a inhibited KPNB1 by targeting the KPNB1 3' untranslated region in MPNST cells. Our data also showed that EZH2 suppressed miR-200b expression and induced epithelial-mesenchymal transition in MPNST cells. These findings demonstrated that DZNep, an inhibitor of S-adenosyl-methionine–dependent methyltransferase, suppressed EZH2/miR-30a,d/KPNB1 signaling and blocked MPNST tumor cell growth and survival in vitro and in vivo. More importantly, our study indicated that pharmacological interference of EZH2 is a potential therapeutic approach for MPNST.
Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age
Authors: S. Lum, J. Kirkby, L. Welsh, N. Marlow, E. Hennessy, J. Stocks
Journal: European Respiratory Journal (2010)

Advances in neonatal care have resulted in increased survival of children born extremely pre-term (EP). Nevertheless the incidence of bronchopulmonary dysplasia and long-term respiratory morbidity remains high. We investigated the nature of pathophysiological changes at 11 yrs of age to ascertain whether respiratory morbidity in EP children primarily reflects alterations in the lung periphery or more centralised airway function in this population. Spirometry, plethysmography, diffusing capacity, exhaled nitric oxide, multiple-breath washout, skin tests and methacholine challenge were used during laboratory-based assessments in a subgroup of the 1995 EPICure cohort and in controls. Results were obtained in 49 EP and 52 control children. Lung function abnormalities were found in 78% of EP children, with evidence of airway obstruction, ventilation inhomogeneity, gas trapping and airway hyperresponsiveness. Levels of atopy and exhaled nitric oxide were similar between the groups. Prior wheeze was associated with significant reductions in forced flows and volumes. By contrast, abnormalities of the lung periphery appear to be mediated primarily through EP birth per se . The prevalence of lung function abnormalities, which is largely obstructive in nature and likely to have long-term implications, remains high among 11-yr-old children born EP. Spirometry proved an effective means of detecting these persistent abnormalities.
Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis
Authors: Suzanne Arends, Cecile Grootscholten, Ronald HWM Derksen, Stefan P Berger, Ruud GL de Sévaux, Alexandre E Voskuyl, Marc Bijl, Jo HM Berden
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> The objectives of this study are to analyse the long-term follow-up of a randomised controlled trial of induction treatment with azathioprine/methylprednisolone (AZA/MP) versus high-dose intravenous cyclophosphamide (ivCY) in patients with proliferative lupus nephritis (LN) and to evaluate the predictive value of clinical, laboratory and renal biopsy parameters regarding renal outcome. <h3>Methods</h3> 87 patients with biopsy-proven proliferative LN were treated with either AZA/MP (n=37) or ivCY (n=50), both with oral prednisone. After 2 years, renal biopsy was repeated, and all patients continued with AZA/oral prednisone. The primary study end point was sustained doubling of serum creatinine. Secondary end points included renal relapse, end-stage renal disease and mortality. <h3>Results</h3> After a median follow-up of 9.6 years, no significant differences between AZA/MP versus ivCY groups were found in the proportion of patients with sustained doubling of serum creatinine (n=6 (16%) vs n=4 (8%); p=0.313), end-stage renal disease (n=2 (5%) vs n=2 (4%); p=1.000) or mortality (n=6 (16%) vs n=5 (10%); p=0.388). Renal relapses occurred more often in the AZA/MP group (n=14 (38%) vs n=5 (10%); p=0.002, HR: 4.5). Serum creatinine, proteinuria and immunosuppressive treatment regimens at the last follow-up were comparable. Clinical and laboratory parameters at baseline and after 2 years, and renal biopsy parameters (only) at baseline predicted renal outcome. <h3>Conclusion</h3> Induction treatment with ivCY was superior to AZA/MP in preventing renal relapses, but other parameters for renal function did not differ. AZA/MP can therefore serve as an alternative in patients with proliferative LN who wish to avoid gonadal toxicity of CY. Several prognostic factors of long-term renal outcome were identified.
Efficacy of high-dose chemotherapy or standard salvage therapy in patients with recurrent medulloblastoma
Authors: Sridharan Gururangan, Jeanne Krauser, Melody A. Watral, Tim Driscoll, Nicole Larrier, David A. Reardon, Jeremy N. Rich, Jennifer A. Quinn, James J. Vredenburgh, Annick Desjardins, Roger E. McLendon, Herbert Fuchs, Joanne Kurtzberg, Henry S. Friedman
Journal: Neuro-Oncology (2008)

The efficacy of high-dose chemotherapy (HDC) or standard salvage therapy was evaluated in patients with recurrent medulloblastoma (MBL) using retrospective chart review of all patients with recurrent MBL treated at Duke University Medical Center between 1995 and 2005 and who had undergone HDC with or without radiotherapy (RT) or standard salvage therapy after relapse. A total of 30 patients were diagnosed with recurrent MBL after standard RT alone or chemotherapy with RT. Nineteen patients (7 who received no RT before recurrence [group A] and 12 who received definitive RT before recurrence [group B]) underwent surgery and/or induction chemotherapy followed by HDC plus autologous stem-cell rescue. Eleven patients (group C) underwent standard salvage therapy. Six of seven group A patients also received standard RT just before or after recovery from HDC, and 5 of 12 group B patients received adjuvant palliative focal RT post-HDC. At a median follow-up of 28 months, three of seven patients in group A are alive and disease-free at ⩾34, ⩾110, and ⩾116 months, respectively, post-HDC. All patients in groups B and C have died of tumor, at a median of 35 months and 26 months from HDC and standard salvage therapy, respectively. HDC or standard salvage therapy was ineffective in our patients with recurrent MBL who had received standard RT before recurrence. The favorable impact of HDC on disease control in the two long-term survivors cannot be clearly established due to the cofounding effect of definitive RT postrecurrence.
Charge changes in protein evolution.
Authors: E W Peetz, G Thomson, P W Hedrick
Journal: Molecular Biology and Evolution (1986)

The number of charge changes relative to total amino acid replacements for each of seven protein sequences (cytochrome c, hemoglobin alpha, hemoglobin beta, myoglobin, insulin, and fibrinopeptides A and B) has been studied. This number was compared with the expected value obtained under the assumption of random nucleotide substitution. The results obtained indicate that four proteins--hemoglobin alpha, hemoglobin beta, myoglobin, and insulin--are accumulating charge changes at rates slower than those predicted by a model of random substitution. Cytochrome c and fibrinopeptides A and B are accumulating charge changes at rates similar to those predicted by a random model.
Low Rates of Testing and Diagnostic Codes Usage in a Commercial Clinical Laboratory
Authors: Lesley A Stevens, George Fares, James Fleming, David Martin, Kalyani Murthy, Jiejing Qiu, Paul C Stark, Katrin Uhlig, Frederick Van Lente, Andrew S Levey
Journal: Journal of the American Society of Nephrology (2005)

Improving outcomes for chronic kidney disease (CKD) requires early identification and recognition by physicians. There are few data on rates of testing or use of diagnostic codes for CKD. A cross-sectional analysis was performed of patients who were older than 40 yr and had one or more laboratory tests between April 1, 2002, and March 31, 2003, at a Laboratory Corporation of America regional laboratory. Objectives were to determine the frequency of testing for serum creatinine; prevalence of CKD, defined as estimated GFR <60 ml/min per 1.73 m2; and sensitivity of diagnostic codes for CKD for patients with and without risk factors for CKD and with or without cardiovascular disease (CVD). Of the 277,111 patients, 19% had serum creatinine measured, compared with 33 and 71% who had measurements of serum glucose and lipids, respectively. Patients with hypertension, diabetes, and age >60 yr were more likely to be tested for serum creatinine with odds ratio (OR; 95% confidence interval) of 2.09 (2.05 to 2.14), 1.22 (1.19 to 1.25), and 1.24 (1.22 to 1.27) respectively. Among patients tested, 30% had CKD. Sensitivity and specificity of kidney disease diagnostic codes compared with CKD defined by estimated GFR <60 ml/min per 1.73 m2 were 11 and 96%, respectively. In patients with hypertension, diabetes, age >60 years, and CVD, rates of testing and sensitivity of diagnostic codes were 53 and 14%, respectively. Low rates of testing for serum creatinine and insensitivity of diagnostic codes for CKD, even in high-risk patients, suggests inadequate physician awareness of CKD and limited utility of administrative databases for identification of patients with CKD.
The Common Cytokine Receptor γ Chain and the Pre-T Cell Receptor Provide Independent but Critically Overlapping Signals in Early α/β T Cell Development
Authors: James P. Di Santo, Iannis Aifantis, Eleftheria Rosmaraki, Corinne Garcia, Jacqueline Feinberg, Hans Jörg Fehling, Alain Fischer, Harald von Boehmer, Benedita Rocha
Journal: The Journal of Experimental Medicine (1999)

Intracellular signals emanating from cytokine and antigen receptors are integrated during the process of intrathymic development. Still, the relative contributions of cytokine receptor signaling to pre-T cell receptor (TCR) and TCR-mediated differentiation remain undefined. Interleukin (IL)-7 interactions with its cognate receptor complex (IL-7Rα coupled to the common cytokine receptor γ chain, γc) play a dominant role in early thymopoiesis. However, α/β T cell development in IL-7–, IL-7Rα–, and γc-deficient mice is only partially compromised, suggesting that additional pathways can rescue α/β T lineage cells in these mice. We have investigated the potential interdependence of γc- and pre-TCR–dependent pathways during intrathymic α/β T cell differentiation. We demonstrate that γc-dependent cytokines do not appear to be required for normal pre-TCR function, and that the rate-limiting step in α/β T cell development in γc− mice does not involve TCR-β chain rearrangements, but rather results from poor maintenance of early thymocytes. Moreover, mice double mutant for both γc and pre-Tα show vastly reduced thymic cellularity and a complete arrest of thymocyte differentiation at the CD44+CD25+ cell stage. These observations demonstrate that the pre-TCR provides the γc-independent signal which allows α/β T cell development in γc− mice. Thus, a series of overlapping signals derived from cytokine and T cell receptors guide the process of α/β thymocyte development.
Cause and Consequence of Cancer/Testis Antigen Activation in Cancer
Authors: Angelique W. Whitehurst
Journal: The Annual Review of Pharmacology and Toxicology (2013)

Tumor cells frequently exhibit widespread epigenetic aberrations that significantly alter the repertoire of expressed proteins. In particular, it has been known for nearly 25 years that tumors frequently reactivate genes whose expression is typically restricted to germ cells. These gene products are classified as cancer/testis antigens (CTAs) owing to their biased expression pattern and their immunogenicity in cancer patients. While these genes have been pursued as targets for anticancer vaccines, whether these reactivated testis proteins have roles in supporting tumorigenic features is less studied. Recent evidence now indicates that these proteins can be directly employed by the tumor cell regulatory environment to support cell-autonomous behaviors. Here, we review the history of the CTA field and present recent findings indicating that CTAs can play functional roles in supporting tumorigenesis.
Matrix Metalloproteinase-7 as a Surrogate Marker Predicts Renal Wnt/β-Catenin Activity in CKD
Authors: Weichun He, Roderick J. Tan, Yingjian Li, Dan Wang, Jing Nie, Fan Fan Hou, Youhua Liu
Journal: Journal of the American Society of Nephrology (2011)

A variety of chronic kidney diseases exhibit reactivation of Wnt/β-catenin signaling. In some tissues, β-catenin transcriptionally regulates matrix metalloproteinase-7 (MMP-7), but the association between MMP-7 and Wnt/β-catenin signaling in chronic kidney disease is unknown. Here, in mouse models of both obstructive nephropathy and focal segmental glomerulosclerosis (adriamycin nephropathy), we observed upregulation of MMP-7 mRNA and protein in a time-dependent manner. The pattern and extent of MMP-7 induction were positively associated with Wnt/β-catenin signaling in these models. Activation of β-catenin through ectopic expression of Wnt1 promoted MMP-7 expression in vivo, whereas delivery of the gene encoding the endogenous Wnt antagonist Dickkopf-1 abolished its induction. Levels of MMP-7 protein detected in the urine correlated with renal Wnt/β-catenin activity. Pharmacologic blockade of Wnt/β-catenin signaling by paricalcitol inhibited MMP-7 expression in diseased kidneys and reduced the levels detected in the urine. In vitro, β-catenin activation induced the expression and secretion of MMP-7 and promoted the binding of T cell factor to the MMP-7 promoter in kidney epithelial cells. We also observed higher levels of MMP-7 expression, which correlated with β-catenin, in kidney tissue from patients with various nephropathies. In summary, levels of renal MMP-7 correlate with Wnt/β-catenin activity, and urinary MMP-7 may be a noninvasive biomarker of this profibrotic signaling in the kidney.