tbuckley/cabot-search huggingface dataset:
Histone Deacetylase (HDAC) Inhibitor LBH589 Increases Duration of γ-H2AX Foci and Confines HDAC4 to the Cytoplasm in Irradiated Non–Small Cell Lung Cancer
Authors: Ling Geng, Kyle C. Cuneo, Allie Fu, Tianxiang Tu, Peter W. Atadja, Dennis E. Hallahan
Journal: Cancer Research (2006)

Abstract Histone deacetylases (HDAC) have been identified as therapeutic targets due to their regulatory function in DNA structure and organization. LBH589 is a novel inhibitor of class I and II HDACs. We studied the effect of LBH589 and ionizing radiation (IR) on DNA repair in two human non–small cell lung cancer (NSCLC) cell lines (H23 and H460). γ-H2AX foci present at DNA double-strand breaks (DSBs) were detected in the nuclei following 3 Gy irradiation for up to 6 hours. LBH589 administered before irradiation increased the duration of γ-H2AX foci beyond 24 hours. Furthermore, radiation alone induced translocation of HDAC4 to the nucleus. In contrast, treatment with LBH589 followed by irradiation resulted in HDAC4 confinement to the cytoplasm, indicating that HDAC inhibition affects the nuclear localization of HDAC4. The findings that LBH589 confines HDAC4 to the cytoplasm and increases the duration of γ-H2AX foci in irradiated cell lines suggest that HDAC4 participates in DNA damage signaling following IR. Annexin-propidium iodide flow cytometry assays, cell morphology studies, and cleaved caspase-3 Western blot analysis revealed a synergistic effect of LBH589 with IR in inducing apoptosis. Clonogenic survival showed a greater than additive effect when LBH589 was administered before irradiation compared with irradiation alone. In vivo tumor volume studies showed a growth delay of 20 days with combined treatment compared with 4 and 2 days for radiation or LBH589 alone. This study identifies HDAC4 as a biomarker of LBH589 activity and recognizes the ability of LBH589 to sensitize human NSCLC to radiation-induced DNA DSBs. (Cancer Res 2006; 66(23): 11298-304)
Nodular regenerative hyperplasia mimicking cirrhosis of the liver.
Authors: J A McDonald, D M Painter, N D Gallagher, G W McCaughan
Journal: Gut (1990)

Nodular regenerative hyperplasia of the liver usually presents with signs of portal hypertension with little evidence of obvious liver disease. We report a 47 year old man who presented with clinical signs of decompensated cirrhosis, recurrent encephalopathy, and tense ascites but at liver transplant was found to have nodular regenerative hyperplasia associated with a portal vein thrombosis.
Seasonal variations in the body composition of lightweight rowers.
Authors: F L Morris, W R Payne
Journal: British Journal of Sports Medicine (1996)

OBJECTIVE: To monitor the seasonal body composition alterations in 18 lightweight rowers (six females, 12 males) across a rowing season incorporating preseason, early competition, competition, and postseason. METHODS: Subject age was 23.1 (SD 4.5) years, height 170.8 (5.6) cm (female, 23.5 (3.5) years, 180.5 (2.7) cm (male). Body weight, fat mass, and fat-free mass (FFM) were assessed using dual energy x ray absorptiometry (DXA-L Lunar) and skinfold techniques. Weight control techniques were documented before major regattas by a questionnaire. RESULTS: Female body weight was reduced from 61.3 (2.9) to 57.0 (1.1) kg (5.9%), while male body weight was reduced from 75.6 (3.1) to 69.8 (1.6) kg (7.8%) preseason to competition season respectively. These body weight reductions were mirrored by a significant reduction in fat mass as indicated by the sum of skinfolds [female seven sites: 80.9 (8.1) to 68.2 (11.8) mm; male eight sites: 54.2 (8.7) to 41.8 (4.8) mm], percentage body fat [female 22.1 (1.0) to 19.7 (2.4)%; male 10.0 (0.9) to 7.8 (0.8)%], and total fat [female 12.5 (5.2) to 10.9 (1.4) kg; male 7.3 (1.9) to 5.6 (1.8) kg] (DXA). In contrast, no changes were observed in FFM despite a season of intensive rowing training. Seasonal body weight control was achieved through reduced total energy and dietary fat intakes. Acute body weight reductions were achieved by exercise in 73.3% of participants, food restriction in 71.4%, and fluid restrictions in 62.9%. CONCLUSIONS: Seasonal body weight alterations in lightweight rowers are in response to a significant reduction in fat mass. However, the weight restrictions appear to be limiting an increase in FFM which could be beneficial to rowing performance.
The Vectorcardiogram in Cystic Fibrosis
Authors: JEROME LIEBMAN, CARL F. DOERSHUK, CLYDE RAPP, LEROY MATTHEWS
Journal: Circulation (1967)

One hundred and one children with cystic fibrosis had detailed studies of the vectorcardiograms and pulmonary function tests. The vectorcardiographic diagnoses were (1) right ventricular hypertrophy (14 patients), (2) right ventricular hypertrophy plus abnormally posterior vector (24 patients), (3) abnormally posterior vector (26 patients), (4) low voltage (nine patients), and (5) tracing within normal limits (35 patients). Right ventricular hypertrophy correlated well with a decreased vital capacity. Abnormally posterior vector correlated well with increased residual volume and functional residual capacity. The presence of the abnormally posterior vector was demonstrated to be the major factor in the difficulty in interpreting right ventricular hypertrophy from the electrocardiogram, for a large terminal rightward vector was often too far posterior to be registered as a terminal R in the right chest leads. The Frank system vectorcardiogram was demonstrated to be better able to detect right ventricular hypertrophy than was the cube system vectorcardiogram. This was particularly true in the presence of an abnormally posterior vector. An abnormally leftward 0.01-second vector, if it is anterior, is frequently seen in right ventricular hypertrophy.
18F-DOPA PET/CT in the Evaluation of Hereditary SDH-Deficiency Paraganglioma-Pheochromocytoma Syndromes
Authors: Maria Cristina Marzola, Sotirios Chondrogiannis, Gaia Grassetto, Lucia Rampin, Anna Margherita Maffione, Alice Ferretti, Giuseppe Opocher, Francesca Schiavi, Patrick M. Colletti, Domenico Rubello
Journal: Clinical Nuclear Medicine (2013)

This study aims to evaluate the role of F-DOPA PET/CT in staging and follow-up of paraganglioma syndromes succinate dehydrogenase (SDH)-mutation-related patients, comparing F-DOPA PET/CT results with morphological imaging and biochemical results.We retrospectively studied 10 consecutive patients (3 F, 7 M, mean age 32 yrs), all with a genetically demonstrated SDH mutation (5 SDH-D, 4 SDH-B, and 1 SDH-C) and all addressed to F-DOPA PET/CT scan. Seven patients had already been operated on for one or more pheochromocytomas and/or paragangliomas and were submitted to F-DOPA PET/CT scan according to clinical, biochemical, or radiological suspicion of recurrence, while 3 were only genetically positive, with no previous symptom/sign of the disease. For all patients, biochemical analysis (plasma and/or urinary catecholamine) and results of high-resolution morphological imaging studies (CT and/or MRI) were available. Histologic/cytologic findings or imaging and biochemical follow-up were taken as gold standard in all cases.Seven out of 10 patients showed one or more areas of pathological F-DOPA accumulation. PET/CT demonstrated the presence of the disease in 4/6 patients with no increase in catecholamine levels ("biochemically silent"). Positive detection rate was 100% in SDH-D and 40% in "non-SDHD". Analyzing per lesion, F-DOPA PET/CT demonstrated more lesions than anatomical imaging (16 vs. 7) especially in head and neck paragangliomas.F-DOPA PET/CT seems to be the more accurate method for staging and restaging patients with SDH-mutations-related paraganglioma syndromes. F-DOPA is particularly useful in detecting head and neck and biochemically silent paragangliomas, and also in apparently healthy mutation-carrying people.
Immunophenotyping and T-cell receptor γ gene rearrangement analysis as an adjunct to the histopathologic diagnosis of mycosis fungoides
Authors: Reuven Bergman, Doron Faclieru, Dvora Sahar, Christian A. Sander, Hedviga Kerner, Yehudith Ben-Aryeh, Lena Manov, Eti Hertz, Edmond Sabo, Rachel Friedman-Birnbaum
Journal: Journal of the American Academy of Dermatology (1998)
Deforming arthritis in systemic lupus erythematosus.
Authors: J M Esdaile, D Danoff, L Rosenthall, A Gutkowski
Journal: Annals of the Rheumatic Diseases (1981)

Low brain accumulation of anticancer drugs due to efflux transporters may limit chemotherapeutic efficacy, necessitating better understanding of the underlying mechanisms. P-glycoprotein (Abcb1a/1b) and breast cancer resistance protein (Abcg2) combination knockout mice often display disproportionately increased brain accumulation of shared drug substrates compared to single transporter knockout mice. Recently developed pharmacokinetic models could explain this phenomenon. To experimentally test these models and their wider relevance for tyrosine kinase inhibitors (TKIs) and other drugs, we selected dasatinib, sorafenib and sunitinib because of their divergent oral availability and brain accumulation profiles: brain accumulation of dasatinib is mainly restricted by Abcb1, that of sorafenib mainly by Abcg2, and that of sunitinib equally by Abcb1 and Abcg2. We analyzed the effect of halving the efflux activity of these transporters at the blood-brain barrier (BBB) by generating heterozygous Abcb1a/1b;Abcg2 knockout mice, and testing plasma and brain levels of the drugs after oral administration at 10 mg/kg. RT-PCR analysis confirmed ~2-fold decreased expression of both transporters in brain. Interestingly, whereas complete knockout of the transporters caused 24- to 36-fold increases in brain accumulation of the drugs, the heterozygous mice only displayed 1.6- to 1.9-fold increases of brain accumulation relative to wild-type mice. These results are well in line with the predictions of the pharmacokinetic models, and provide strong support for their validity for a wider range of drugs. Moreover, retrospective analysis of fetal accumulation of drugs across the placenta in Abcb1a/1b heterozygous knockout pups suggests that these models equally apply to the maternal-fetal barrier.
Needle aspiration of amoebic liver abscess.
Authors: M. P. Sharma, R. R. Rai, S. K. Acharya, J. C. Ray, B. N. Tandon
Journal: BMJ (1989)

OBJECTIVE--To determine the value of needle aspiration in uncomplicated amoebic liver abscess. DESIGN--Randomised case-control study with a minimum follow up of one year, comparing patients treated with drugs alone with those treated with additional needle aspiration. SETTING--Referral based gastroenterology clinic. PATIENTS--39 Consecutive patients with amoebic liver abscess in the right lobe, of whom 37 completed the study. INTERVENTION--Metronidazole 2.4 g/day was given to all patients for 10 days. Needle aspiration of the abscess was performed in 19 patients on the day of admission to hospital. MAIN OUTCOME MEASURES--Abdominal pain, fever, anorexia, and hepatomegaly were measured. Erythrocyte sedimentation rate, serum aspartate, and alanine aminotransferase activities, and alkaline phosphatase activity were also measured. RESULTS--Clinical improvement was similar in both groups of patients. Improvement in haematological and biochemical variables and rates of healing of cavities were also similar. CONCLUSIONS--Chemotherapy with potent tissue amoebicidal drugs such as metronidazole is optimally effective in treating amoebic liver abscess, and in uncomplicated cases routine aspiration is not required.
Diagnosing bronchioloalveolar carcinoma.
Authors: F. G. Mayall
Journal: BMJ (1992)

whether any otorrhoea had occurred.No attempt was made to correlate the otorrhoea to swimming activity or upper respiratory infection.We studied 210 children (mean age 6 years).At the beginning of the summer the tubes had been in place for a mean of six months (range one to 24 months).Purulent discharge developed in 40 patients, 20 of whom had not been swimming.The incidence of otorrhoea was lower in the 142 children who had swum during the summer (13'S,) than in the 68 children who had not (31 %) (p=0-005, X2 test).The incidence of infection in the group who had not swum was not significantly different from that in the 27 children who had swum one to five times (33%) but was significantly higher than that in the 41 children who had gone swimming six to 20 times (12%, p=0 01) and in the 71 children who had gone swimming more than 20 times (7%, p<0-001).Our conclusions are the same as those ofPringle': children with grommets should be allowed to swim.Penetration of water into the ear canal is not the main factor leading to otorrhoea in patients with grommets.
Abstract 5047: Impact of kidney progenitor cell differentiation status in Wilms tumorigenesis.
Authors: Le Huang, Sharada Mokkapati, Qianghua Hu, Vicki Huff
Journal: Cancer Research (2013)

Abstract Wilms Tumor (WT) is a pediatric cancer of the kidney and one of the most common solid tumors of childhood. It is thought to arise from the undifferentiated renal mesenchyme, however, it is unknown which mesenchymal cell type can give rise to WT. The recent identification of different subsets of human WTs with defined gene expression signature, histology and clinical outcomes suggests that the cell differentiation status may be an important factor in the etiology of these subsets. Therefore, we hypothesize that WT can arise from fetal kidney cells at different differentiation stages and that different progenitor populations will result in different types of tumors in biology, pathology and molecular signature. Our lab has generated the first genetic WT mouse model via somatic and mosaic ablation of Wilms Tumor 1 (Wt1), using a Wt1 conditional knockout allele with a ubiquitous tamoxifen-inducible CGH-Cre, and Igf2 biallelic expression. In this model, all types of embryonic kidney cells were randomly targeted. With this successful approach, we now have the ability to test the effect of introducing these alterations (Wt1 ablation in the context of Igf2 up-regulation or activation of β-Catenin) into kidney nephrogenic (Cited1-CreERT2) or stromagenic (Foxd1-CreERT2) progenitor cells. Very interestingly, when the mutations were introduced into the nephrogenic progenitors (Cited1-CreERT), WTs develop. These tumors express human WT markers and show a tubular histology with predominant epithelial cells, which histologically corresponds to the epithelial subset of human WTs. To further characterize the biology of these tumors, we will perform gene expression analysis and proteomic microarray analysis to identify aberrantly dysregulated signaling pathways. This study will provide insight into the cellular etiology of WT which may help to identify new therapeutic approaches. Citation Format: Le Huang, Sharada Mokkapati, Qianghua Hu, Vicki Huff. Impact of kidney progenitor cell differentiation status in Wilms tumorigenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5047. doi:10.1158/1538-7445.AM2013-5047
From the authors
Authors: C. G. Cote
Journal: European Respiratory Journal (2008)

We have read with interest the observations by G.G. Riario Sforza and C. Incorvaia regarding the differences in the threshold values used to predict mortality that were provided by Lederer et al. 1 for patients with idiopathic pulmonary fibrosis (IPF) and those that were reported for patients with chronic obstructive pulmonary disease (COPD) 2.

First, G.G. Riario Sforza and C. Incorvaia correctly point out that Lederer et al. 1 quote a threshold of 207 m as being more specific for waiting-list mortality at 6 months but, in the …
145 VIRAL ENTRY AND ESCAPE FROM ANTIBODY-MEDIATED NEUTRALIZATION ARE KEY DETERMINANTS FOR THE SELECTION OF HEPATITIS C VIRUS VARIANTS DURING LIVER TRANSPLANTATION
Authors: S. Fafi-Kremer, E. Soulier, I. Fofana, P. Carolla, M. Bastien-Vale, E. Schvoerer, C. Schuster, F. Schramm, F.-L. Cosset, D. Jaeck, M. Doffoel, P. Wolf, F. Stoll-Keller, T. Baumert
Journal: Journal of Hepatology (2008)
The jigsaw of child protection
Authors: Finlay Scott
Journal: Journal of the Royal Society of Medicine (2008)

Heather Payne cites two cases involving Dr David Southall in her article ‘The jigsaw of child protection’ (JRSM 2008;101:93–94). She uses these to advance general propositions about the role and operation of the GMC. Dr David Southall has appealed the more recent decision to the High Court. It would be inappropriate for me to comment on either case in advance of that appeal. But there is a more general point about the way that the GMC’s critics allow a very small number of specific cases to dominate their arguments and skew their assertions about how paediatricians are treated by the GMC.

The GMC’s statutory purpose is to protect, promote and maintain the health and safety of the public by ensuring proper standards in the practice of medicine. We investigate complaints about individual doctors in order to establish whether their fitness to practise is impaired.

Paediatricians attract complaints like other doctors, but it is untrue that large or disproportionate numbers of paediatricians are represented in our fitness-to-practise procedures or that other than a very small number are referred for a public hearing.

Between April 2006 and April 2008, we received 9400 enquiries or complaints about doctors of all specialities. Of those we investigated, 14 were about paediatricians allegedly in connection with child protection work. 11 of the 14 have concluded without reference to a fitness-to-practice panel or other action by the GMC. Three investigations have not yet been concluded.

It is actually extremely rare for a paediatrician to appear before a panel in connection with child protection work. Since 2004, panels have considered more than 600 cases. Only two could reasonably be said to have been about paediatricians involved in child protection. We agree it cannot be in the public interest if doctors are inhibited from acting to protect children or deterred from giving evidence honestly and truthfully and within their competence. But, equally, it cannot be in the public interest, or the interests of the medical profession, if the GMC does not act when doctors practise incompetently or inappropriately.
SQSTM1 Is a Pathogenic Target of 5q Copy Number Gains in Kidney Cancer
Authors: Lianjie Li, Chuan Shen, Eijiro Nakamura, Kiyohiro Ando, Sabina Signoretti, Rameen Beroukhim, Glenn S. Cowley, Patrick Lizotte, Ella Liberzon, Steven Bair, David E. Root, Pablo Tamayo, Aviad Tsherniak, Su-Chun Cheng, Barbara Tabak, Anders Jacobsen, A. Ari Hakimi, Nikolaus Schultz, Giovanni Ciriello, Chris Sander, James J. Hsieh, William G. Kaelin
Journal: Cancer Cell (2013)
Marrow Transplantation in Patients with Advanced Thalassemia
Authors: Guido Lucarelli, Mariella Galimberti, Paola Polchi, Claudio Giardini, Patricia Politi, Donatella Baronciani, Emanuele Angelucci, Fla via Manenti, Constante Delfini, Giovanni Aureu, Pietro Muretto
Journal: New England Journal of Medicine (1987)

In a study of the outcome of marrow transplantation in patients with advanced thalassemia, 40 patients with homozygous beta-thalassemia who were 8 to 15 years of age (median, 10) received HLA-identical allogeneic marrow after treatment with busulfan and cyclophosphamide. Twenty-eight of the 40 patients were alive and free of disease 260 to 939 days after transplantation, and 2 patients were alive with thalassemia 372 and 1133 days after transplantation. The actuarial probabilities of survival and of disease-free survival at two years were 75 percent and 69 percent, respectively. Ten patients (25 percent) died. Three died of cardiac failure, interstitial pneumonitis, or septicemia within 14 days of transplantation. Three died of infectious complications associated with acute graft-versus-host disease at 46 to 97 days, and two died of infectious complications of chronic graft-versus-host disease at 249 and 290 days. Two patients had transplant rejection and died with marrow aplasia 115 and 192 days after transplantation. One patient had rejection after four months and while the marrow was aplastic underwent a successful second transplantation; the patient was alive without thalassemia 624 days after the first transplantation. The actuarial probability of grade 2 or higher acute graft-versus-host disease in the 32 patients with initial sustained engraftment was 35 percent. Three patients had chronic graft-versus-host disease, which was fatal in two and still active on day 710 in the third. We conclude that bone marrow transplantation can potentially save patients with advanced thalassemia from an otherwise inexorable progression to death from the complications of blood transfusions. The ultimate outcome in this group of patients must await a longer follow-up.
Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids
Authors: Courtney B. Ferrebee, Paul A. Dawson
Journal: Acta Pharmaceutica Sinica B (2015)

The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor (FXR) and the G-protein-coupled bile acid receptor (TGR5).
Commercial Nanoparticles for Stem Cell Labeling and Tracking
Authors: Yaqi Wang, Chenjie Xu, Hooisweng Ow
Journal: Theranostics (2013)

Stem cell therapy provides promising solutions for diseases and injuries that conventional medicines and therapies cannot effectively treat.To achieve its full therapeutic potentials, the homing process, survival, differentiation, and engraftment of stem cells post transplantation must be clearly understood.To address this need, non-invasive imaging technologies based on nanoparticles (NPs) have been developed to track transplanted stem cells.Here we summarize existing commercial NPs which can act as contrast agents of three commonly used imaging modalities, including fluorescence imaging, magnetic resonance imaging and photoacoustic imaging, for stem cell labeling and tracking.Specifically, we go through their technologies, industry distributors, applications and existing concerns in stem cell research.Finally, we provide an industry perspective on the potential challenges and future for the development of new NP products.