tbuckley/cabot-search huggingface dataset:
Novel methods for generating fractional epidermal micrografts
Authors: M. Purschke, F.A. Asrani, S.A. Sabir, W.A. Farinelli, R.R. Anderson
Journal: British Journal of Dermatology (2014)

Epidermal suction blister grafts are an effective treatment for chronic wounds or vitiligo, but this treatment is time consuming and limited to small areas.To compare two novel strategies to create fractional epidermal grafts.Epidermal blisters were raised from fresh human skin ex vivo at 38-40 °C, with suction of 380-510 mmHg. In Strategy 1, a 1-cm blister was micromeshed into approximately 500 pieces, transferred to elastic adhesive dressing, then pneumatically expanded to approximately nine times the original blister area. In Strategy 2, a 25-cm(2) array of 100 small blisters was raised, simultaneously harvested and captured directly onto an adhesive dressing. Measurements were taken for the pneumatic expansion limit, the release of microblisters upon hydration of the dressing adhesive, light microscopy, epidermal cell viability and positive L-3,4 dihydroxyphenylalanine melanocyte presence in blisters.Both strategies yielded viable fractional epidermal microblister arrays, carried on a dressing for transfer to graft recipient sites. The microblisters were gradually released upon hydration of the dressing adhesive. Strategy 2 has major advantages as only small blisters are made at the donor site, skilful dissection and physical expansion are not required and the strategy can be scaled to create large-area grafts.Strategy 2 is the more practical method for fractional epidermal micrografting to treat larger lesions with less donor-site trauma and has recently been commercialized.
Bortezomib treatment causes long-term testicular dysfunction in young male mice
Authors: Mi Hou, Emma Eriksson, Konstantin Svechnikov, Kirsi Jahnukainen, Olle Söder, Andreas Meinhardt, Lars Sävendahl
Journal: Molecular Cancer (2014)

With increased long-term survivors of childhood cancer patients, therapy-associated infertility has become one of the most common late side-effects and significantly affects their life-quality. Therefore, evaluation of anti-cancer agents on male reproduction and infertility prevention are urgently demanding. The proteasome inhibitor bortezomib has been launched in clinical trials for childhood cancers, however, its potential side effects on reproduction have so far been neither investigated experimentally nor reported in treated children. Thus the present study is designed to explore the impact of bortezomib on male reproductive function and to gain insights into how bortezomib exerts its adverse effects on man gonad, thereby providing pediatric oncologists relevant information. 35 day-old male mice were treated with one 11-day cycle of bortezomib and then sacrificed 2 days, 45 days, or 6 months later. A mating study was performed in the group followed for 6 months, and their pups were analyzed on postnatal day 50. Serum follicle-stimulating hormone (FSH) and testicular testosterone levels were measured. Testicular morphology was evaluated by light- and electron microscopy, and the underlying mechanisms and pathways of testis damage were investigated. Testicular damage was visible already 2 days after stopping bortezomib and increased in severity by day 45. Then 80% of seminiferous tubules exhibited hypospermatogenesis with arrest at the levels of spermatogonia, spermatocytes and round spermatids. Germ cells were specifically targeted by bortezomib as evidenced by increased apoptosis mediated through activation of p53 and caspases. Even six months after the bortezomib treatment, testis weight, sperm concentration and seminiferous tubule length remained at a decreased level, indicating that spermatogenesis and tubular outgrowth could not fully recover. Combined with persistently increased serum levels of FSH in these mice, our results demonstrate that bortezomib can have long-term effects on testicular function, although fertility of bortezomib-exposed males remained and their offspring looked healthy. Bortezomib treatment causes long-term gonadal dysfunction in male mice. Careful monitoring of gonadal function in male childhood cancer patients treated with bortezomib is thus strongly recommended.
Acute Monocytic Leukemia (French-American-British classification M5) Does Not Have a Worse Prognosis Than Other Subtypes of Acute Myeloid Leukemia: A Report From the Eastern Cooperative Oncology Group
Authors: Martin S. Tallman, Haesook T. Kim, Elisabeth Paietta, John M. Bennett, Gordon Dewald, Peter A. Cassileth, Peter H. Wiernik, Jacob M. Rowe
Journal: Journal of Clinical Oncology (2004)

Purpose Acute monocytic leukemia is a distinct subtype of acute myeloid leukemia (AML) with characteristic biologic and clinical features. This study was designed to compare the outcome of patients with M5 to that of other subtypes of AML, and to identify differences in M5a and M5b. Patients and Methods We reviewed all patients with AML M5 entered in three clinical trials for newly diagnosed AML conducted by the Eastern Cooperative Oncology Group between 1989 and 1998. Eighty-one patients, 21 with M5a and 60 with M5b, were identified. Results The complete remission rate was 62% for all patients with M5; 52% for patients with M5a and 65% for patients with M5b (P = .3), and 60% for the 1,122 patients with non-M5 AML entered on the same clinical trials (P = .8 for M5 v non-M5). The 3-year disease-free survival was 26% for all M5 patients; 18% for M5a and 28% for M5b (P = .31), and 33% for non-M5 patients (P = .13 for M5 v non-M5). The 3-year overall survival was 31% for all M5 patients; 33% for M5a and 30% for M5b (P = .65), and 30% for non-M5 (P = .74 for M5 v non-M5). The karyotypes of patients with AML M5 were heterogeneous. CD11b was the only leukemic cell antigen expressed differently in M5a (53%) compared to M5b (77%) to a significant degree (P = .02). Conclusion AML M5 represents an immunologically heterogeneous population similar to non-M5 AML with a prognosis that is not dependent on morphology. The disease-free survival and overall survival of patients with M5a, M5b, and non-M5 appear not to differ with currently available therapy.
The Biology of Chemokines and their Receptors
Authors: Devora Rossi, Albert Zlotnik
Journal: Annual Review of Immunology (2000)

During the last five years, the development of bioinformatics and EST databases has been primarily responsible for the identification of many new chemokines and chemokine receptors. The chemokine field has also received considerable attention since chemokine receptors were found to act as co-receptors for HIV infection ( 1 ). In addition, chemokines, along with adhesion molecules, are crucial during inflammatory responses for a timely recruitment of specific leukocyte subpopulations to sites of tissue damage. However, chemokines and their receptors are also important in dendritic cell maturation ( 2 ), B ( 3 ), and T ( 4 ) cell development, Th1 and Th2 responses, infections, angiogenesis, and tumor growth as well as metastasis ( 5 ). Furthermore, an increase in the number of chemokine/receptor transgenic and knock-out mice has helped to define the functions of chemokines in vivo. In this review we discuss some of the chemokines’ biological effects in vivo and in vitro, described in the last few years, and the implications of these findings when considering chemokine receptors as therapeutic targets.
Differential Effects of Paroxetine on Fatigue and Depression: A Randomized, Double-Blind Trial From the University of Rochester Cancer Center Community Clinical Oncology Program
Authors: Gary R. Morrow, Jane T. Hickok, Joseph A. Roscoe, Richard F. Raubertas, Paul L.R. Andrews, Patrick J. Flynn, Harry E. Hynes, Tarit K. Banerjee, Jeffrey J. Kirshner, David K. King
Journal: Journal of Clinical Oncology (2003)

Fatigue and depression typically occur together in cancer patients, suggesting a common etiology, perhaps based on serotonin. This randomized clinical trial tested whether paroxetine, a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin, would reduce fatigue in cancer patients and whether any reduction was related to depression.Cancer patients undergoing chemotherapy for the first time were assessed for fatigue. Of 704 patients who reported fatigue at their second chemotherapy cycle, 549 patients were randomly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks. The assessments of fatigue and depression were performed at cycles 3 and 4 of chemotherapy.A total of 244 patients treated with paroxetine and 235 patients treated with placebo provided assessable data. No difference was detected in fatigue between patient groups. At the end of the study, there was a difference between groups in the mean level of depression (Center for Epidemiologic Studies Depression scores, 12.0 v 14.8, respectively; P <.01).Paroxetine had no influence on fatigue in patients receiving chemotherapy. A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels.
Binding of A <sub>1</sub> Adenosine Receptor Ligand [ <sup>3</sup> H]8-Cyclopentyl-1,3-Dipropylxanthine in Coronary Smooth Muscle
Authors: Tahir Hussain, S. Jamal Mustafa
Journal: Circulation Research (1995)

Abstract Vascular smooth muscle has been reported to contain the A 1 subtype of adenosine receptors, but the existence of such receptor(s) in coronary smooth muscle has not been established. In the present study, the 3 H-labeled A 1 -selective antagonist [ 3 H]8-cyclopentyl-1,3-dipropylxanthine ([ 3 H]DPCPX) was used to demonstrate the specific binding in porcine coronary artery smooth muscle membranes. The binding was saturable with a B max of 6.43±1.02 fmol/mg protein. Scatchard analysis of the binding data provided a single binding site with a K d of 0.21±0.025 nmol/L. In the competition experiments, adenosine receptor agonists and antagonists showed the following order of potency (nmol/L): S - N 6 -(2-endo-norbornyl)adenosine (S-ENBA) 0.11= R (−)- N 6 -phenylisopropyladenosine 0.32&gt;DPCPX 3.2=xanthine amine congener 2.4= N 6 -cyclopentyladenosine 2.67&gt;5′-( N -ethylcarboxamido)-adenosine 7.35&gt;&gt;2-[ p -(2-carboxyethyl)-phenethyl-amino]-5′-( N -ethylcarboxamido)-adenosine 1000&gt;theophylline 83 000. This order of potency fits the criteria for the A 1 adenosine receptor. S-ENBA, a highly selective A 1 receptor agonist, was used to investigate the effect on isoproterenol-mediated vasorelaxation and cAMP accumulation. S-ENBA (0.1 to 10 nmol/L) dose-dependently shifted the isoproterenol-mediated (10 −8 to 10 −5 mol/L) vasorelaxation to the right in vascular rings. S-ENBA (10 nmol/L) inhibited the basal cAMP levels by 36% and attenuated the isoproterenol (10 −5 mol/L)–stimulated cAMP by 25% in the coronary rings. These inhibitory effects of S-ENBA on isoproterenol-mediated cAMP-accumulation and vasorelaxation were abolished by pertussis toxin (100 ng/mL, overnight) treatment of the arteries. Similarly, the effects of S-ENBA on isoproterenol-mediated responses were antagonized by DPCPX. This study provides the evidence suggesting the existence of A 1 adenosine receptors linked to adenylyl cyclase in an inhibitory manner through pertussis toxin–sensitive G proteins in the coronary artery.
Serum cholestanol, cholesterol precursors, and plant sterols during placebo-controlled treatment of primary biliary cirrhosis with ursodeoxycholic acid or colchicine
Authors: Tatu A. Miettinend, Martti Färkkilä, Matti Vuoristo, Anna-Liisa Karvonen, Rauli Leino, Juhani Lehtola, Claes Friman, Kari Seppälä, Juhani Tuominen
Journal: Hepatology (1995)

A randomized placebo-controlled 2-year study was performed in 69 patients with primary biliary cirrhosis (PBC) on serum lipids during ursodeoxycholic acid (URSO) and colchicine treatments. In addition to serum bilirubin and alkaline phosphatase (AFOS), two variables considered to reflect liver function, serum lipoproteins, cholesterol precursors (squalene, delta 8-cholestenol, lathosterol and desmosterol), markers of cholesterol synthesis, cholestanol and plant sterols (campesterol and sitosterol), markers of liver function and cholesterol absorption, were studied before and during the treatments. Serum bilirubin was inconsistently improved by URSO, whereas improvement of AFOS values was better by URSO than colchicine, especially in patients with initially more advanced PBC. Serum total cholesterol was reduced by both drugs, very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) cholesterol by URSO. Cholesterol precursor sterols were increased by both URSO and colchicine mainly in patients with initially less severe PBC. On the other hand, the cholestanol values were markedly increased initially, and the values were related to bilirubin during the 2-year period, were further increased in the placebo group, and reduced in the URSO and colchicine groups, so that the improvement was highest in the URSO-treated patients with the severe form of PBC. The increase of the serum plant sterols, particularly that of sitosterol, was retarded by the two drugs so that the campesterol/sitosterol ratio, which was related to serum bilirubin, was increased especially in the cases with initially more advanced PBC.(ABSTRACT TRUNCATED AT 250 WORDS)
MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition
Authors: Dai Horiuchi, Leonard Kusdra, Noelle E. Huskey, Sanjay Chandriani, Marc E. Lenburg, Ana Maria Gonzalez-Angulo, Katelyn J. Creasman, Alexey V. Bazarov, James W. Smyth, Sarah E. Davis, Paul Yaswen, Gordon B. Mills, Laura J. Esserman, Andrei Goga
Journal: The Journal of Experimental Medicine (2012)

Estrogen, progesterone, and HER2 receptor-negative triple-negative breast cancers encompass the most clinically challenging subtype for which targeted therapeutics are lacking. We find that triple-negative tumors exhibit elevated MYC expression, as well as altered expression of MYC regulatory genes, resulting in increased activity of the MYC pathway. In primary breast tumors, MYC signaling did not predict response to neoadjuvant chemotherapy but was associated with poor prognosis. We exploit the increased MYC expression found in triple-negative breast cancers by using a synthetic-lethal approach dependent on cyclin-dependent kinase (CDK) inhibition. CDK inhibition effectively induced tumor regression in triple-negative tumor xenografts. The proapoptotic BCL-2 family member BIM is up-regulated after CDK inhibition and contributes to this synthetic-lethal mechanism. These results indicate that aggressive breast tumors with elevated MYC are uniquely sensitive to CDK inhibitors.
TCT-145 The significance of VARC-defined acute kidney injury after transcatheter aortic valve implantation using the balloon-expandable Edwards bioprosthesis
Authors: Muhammed Khawaja, Martyn Thomas, Abhishek Joshi, Kaleab Asrress, Karen Wilson, Kirsty Bolter, Jane Hancock, Christopher Young, Vinayak Bapat, Simon Redwood
Journal: Journal of the American College of Cardiology (2012)
Fitness levels and physical activity among class A drug users entering prison
Authors: Jan Fischer, Christine Butt, Helen Dawes, Charlie Foster, Joanne Neale, Emma Plugge, Carly Wheeler, Nat Wright
Journal: British Journal of Sports Medicine (2012)

Background Physical activity could benefit drug users' physiological and mental health. Previous research has suggested that physical activity levels change when drug users enter prison. Methods Twenty-five class A drug users who were new to prison answered physical activity and drug use cross-sectional questionnaires, took a submaximal fitness test and wore a pedometer for 1 week. Results Participants' mean aerobic capacity was estimated as 49 mls O2/kg/min (±12 SD). Their mean self-reported walking distance outside of prison was 4.67 miles on an average day (±4.14 SD). Pedometer data suggest they walked a mean of 1.8 miles/day in prison. Conclusion Many class A drug users entering prison had high levels of fitness and physical activity before admission, often gained from walking. Walking activity reduced when they entered prison, posing a challenge to maintaining healthy activity levels.
Prediction model for knee osteoarthritis incidence, including clinical, genetic and biochemical risk factors
Authors: H J M Kerkhof, S M A Bierma-Zeinstra, N K Arden, S Metrustry, M Castano-Betancourt, D J Hart, A Hofman, F Rivadeneira, E H G Oei, Tim D Spector, A G Uitterlinden, A C J W Janssens, A M Valdes, J B J van Meurs
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To develop and validate a prognostic model for incident knee osteoarthritis (KOA) in a general population and determine the value of different risk factor groups to prediction. <h3>Methods</h3> The prognostic model was developed in 2628 individuals from the Rotterdam Study-I (RS-I). Univariate and multivariate analyses were performed for questionnaire/easily obtainable variables, imaging variables, genetic and biochemical markers. The extended multivariate model was tested on discrimination (receiver operating characteristic curve and area under the curve (AUC)) in two other population-based cohorts: Rotterdam Study-II and Chingford Study. <h3>Results</h3> In RS-I, there was moderate predictive value for incident KOA based on the genetic score alone in subjects aged &lt;65 years (AUC 0.65), while it was only 0.55 for subjects aged ≥65 years. The AUC for gender, age and body mass index (BMI) in prediction for KOA was 0.66. Addition of the questionnaire variables, genetic score or biochemical marker urinary C-terminal cross-linked telopeptide of type II collagen to the model did not change the AUC. However, when adding the knee baseline KL score to the model the AUC increased to 0.79. Applying external validation, similar results were observed in the Rotterdam Study-II and the Chingford Study. <h3>Conclusions</h3> Easy obtainable 'Questionnaire' variables, genetic markers, OA at other joint sites and biochemical markers add only modestly to the prediction of KOA incidence using age, gender and BMI in an elderly population. Doubtful minor radiographic degenerative features in the knee, however, are a very strong predictor of future KOA. This is an important finding, as many radiologists do not report minor degenerative changes in the knee.
The Psychology of Hallucinogenic Drug Discontinuers
Authors: CARL SALZMAN, GERALD E. KOCHANSKY, RICHARD I. SHADER, JONATHAN LIEFF
Journal: American Journal of Psychiatry (1972)

Psychological test data from individuals who had discontinued using hallucinogens with those from individuals who were still using them were compared. While the continuers had a tendency toward higher risk-taking behavior, the two samples could not be otherwise psychologically differentiated. Between two subsamples with moderate drug experience, the continuers showed a greater trend toward psychiatric impairment than the discontinuers. The authors do not believe that drug experiences impaired the discontinuers.
Sequencing and analysis of an Irish human genome
Authors: Pin Tong, James GD Prendergast, Amanda J Lohan, Susan M Farrington, Simon Cronin, Nial Friel, Dan G Bradley, Orla Hardiman, Alex Evans, James F Wilson, Brendan Loftus
Journal: Genome biology (2010)

Recent studies generating complete human sequences from Asian, African and European subgroups have revealed population-specific variation and disease susceptibility loci. Here, choosing a DNA sample from a population of interest due to its relative geographical isolation and genetic impact on further populations, we extend the above studies through the generation of 11-fold coverage of the first Irish human genome sequence. Using sequence data from a branch of the European ancestral tree as yet unsequenced, we identify variants that may be specific to this population. Through comparisons with HapMap and previous genetic association studies, we identified novel disease-associated variants, including a novel nonsense variant putatively associated with inflammatory bowel disease. We describe a novel method for improving SNP calling accuracy at low genome coverage using haplotype information. This analysis has implications for future re-sequencing studies and validates the imputation of Irish haplotypes using data from the current Human Genome Diversity Cell Line Panel (HGDP-CEPH). Finally, we identify gene duplication events as constituting significant targets of recent positive selection in the human lineage. Our findings show that there remains utility in generating whole genome sequences to illustrate both general principles and reveal specific instances of human biology. With increasing access to low cost sequencing we would predict that even armed with the resources of a small research group a number of similar initiatives geared towards answering specific biological questions will emerge.
GEMS (Gene Expression Metasignatures), a Web Resource for Querying Meta-analysis of Expression Microarray Datasets: 17β-Estradiol in MCF-7 Cells
Authors: Scott A. Ochsner, David L. Steffen, Susan G. Hilsenbeck, Edward S. Chen, Christopher Watkins, Neil J. McKenna
Journal: Cancer Research (2008)

With large amounts of public expression microrray data being generated by multiple laboratories, it is a significant task for the bench researcher to routinely identify available datasets, and then to evaluate the collective evidence across these datasets for regulation of a specific gene in a given system. 17beta-Estradiol stimulation of MCF-7 cells is a widely used model in the growth of breast cancer. Although myriad independent studies have profiled the global effects of this hormone on gene expression in these cells, disparate experimental variables and the limited power of the individual studies have combined to restrict the agreement between them as to the specific gene expression signature elicited by this hormone. To address these issues, we have developed a freely accessible Web resource, Gene Expression MetaSignatures (GEMS) that provides the user a consensus for each gene in the system. We conducted a weighted meta-analysis encompassing over 13,000 genes across 10 independent published datasets addressing the effect of 17beta-estradiol on MCF-7 cells at early (3-4 hours) and late (24 hours) time points. In a literature survey of 58 genes previously shown to be regulated by 17beta-estradiol in MCF-7 cells, the meta-analysis combined the statistical power of the underlying datasets to call regulation of these genes with nearly 85% accuracy (false discovery rate-corrected P < 0.05). We anticipate that with future expression microarray dataset contributions from investigators, GEMS will evolve into an important resource for the cancer and nuclear receptor signaling communities.