tbuckley/cabot-search huggingface dataset:
Antimyeloperoxidase-associated Lung Disease
Authors: PASCAL FOUCHER, PETER HEERINGA, ARJEN H. PETERSEN, MINKE G. HUITEMA, ELISABETH BROUWER, JAN W. COHEN TERVAERT, JOCHUM PROP, PHILIP CAMUS, JAN J. WEENING, CEES G. M. KALLENBERG
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The lung is a common target in systemic vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA). In the present study, we tested the hypothesis that the presence of antibodies directed against myeloperoxidase (MPO) induces pulmonary (vasculitic) lesions when neutrophils release lysosomal enzymes. Brown Norway (BN) rats were immunized with human MPO in complete Freund's adjuvant (CFA) or with CFA alone. Two weeks after immunization, rats had developed antibodies to human and rat MPO. Next, isolated single left lung perfusion was performed with human neutrophil lysosomal extract containing MPO and proteolytic enzymes. Rats were killed at 15 min, 4 h, and 10 d after perfusion. Tissue samples from the left and right lung were examined for vasculitic lesions and inflammatory cell infiltrates. At 15 min and 4 h, left lungs from control and MPO-immunized rats showed a mild influx of polymorphonuclear cells. At 10 d, patchy inflammatory cell infiltrates, consisting predominantly of polymorphonuclear leukocytes (PMNs) and monocytes, were observed throughout the parenchyma of the left lung in MPO-immunized rats. Occasionally, granuloma-like lesions, giant cells, and foci of alveolar hemorrhage were observed as well. Far less severe lesions were seen in control immunized rats. Strikingly, at 10 d after perfusion, severe pulmonary tissue injury was observed also in right lungs from MPO-immunized rats whereas right lungs from control immunized rats appeared normal. The lesions were characterized by influx of PMNs and monocytes and, in some rats, foci of alveolar hemorrhage. These studies suggest that the presence of an anti-MPO directed autoimmune response contributes to generalized pulmonary tissue injury after local release of products of activated neutrophils, which supports a pathogenic role of MPO-ANCA.
OP0073 High Risk Fracture in Sarcoidosis Patients Despite Not Lowered Bone Mineral Density: Implication of Serum 25(OH) Vitamin D Levels
Authors: N. Saidenberg-Kermanac’h, L. semerano, H. Nunes, D. Sadoun, X. Guillot, M. Boubaya, N. Naggara, D. Valeyre, M.-C. Boissier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The prevention of fragility fractures in patients with sarcoidosis (Sa) is a serious concern since risk factors are poorly understood and vitamin D (vitD) or calcium prescription is a matter of hesitation in these patients. <h3>Objectives</h3> To evaluate factors increasing the risk of osteoporosis (OP) in Sa. <h3>Methods</h3> We prospectively included 142 consecutive patients with histologically proven Sa. Biological and clinical parameters of Sa activity and severity, BMD (DXA, Lunar Prodigy) and vertebral fracture prevalence on lumbar and thoracic spine (with Genant's semi-quantitative method of) were assessed. <h3>Results</h3> 80 women (51 menopaused) and 62 men, (age 51 ±11.9), with a mean Sa duration of 9.5±7 years were included. 28 patients had never received corticosteroids (CCS), 33 had received vitD supplements, and 46 bisphosphonates, within the 6 months preceding the study. Fragility fractures had occurred in 23.5 % of the patients, (vertebral fractures in 13.7%). 40.1% had BMD T-score &lt;-1DS in at least one site, (20 patients with OP). Nevertheless, the average BMD was not low (mean Tscore -0.44DS at the lumbar spine). VitD supplementation significantly increased serum 25(OH)vitD(p&lt;0.0001)without any significant variation of the calcemia. In multivariate analysis, fracture (OR:3.69, 95%IC, 0.96-14.21, p=0.098), low calcium intake (OR:5.79, 95%IC, 1.82-18.42, p=0.001), and menopause (OR:3.32, 95%IC, 0.67-16.47, p=0.068), were predictive of a low BMD. Age (OR:1.09 95%IC, 1.0-1.18, p=0.021), the NYHA score(OR:3.28 95%IC, 0.79-13.61, p=0.089), the cumulative dose of CCS (OR:1.48, 95%IC, 1.06-2.05, p=0.023), and low BMD (OR:3.75, 95%IC, 0.91-15.36, p=0.093), were predictive of fracture. VitD showed a protective effect on BMD for serum levels between 10 and 20ng/ml (low BMD OR:0.17, 95%0.04-0.83 p=0.028). In a surprising way, values above this threshold were associated with an increased risk of fracture (OR:4.71, 95%IC, 1.01-22.01, p=0.052). Low 25(OH)vitD and not 1.25(OH)2D, was significantly correlated with disease activity parameters (disease flare, ACE, severity of lung involvement, erythrocyte sedimentation rate). <h3>Conclusions</h3> Sa patients have a high risk of fracture despite not lowered BMD. There could be a bimodal relationship between VitD levels and fracture risk. Predictive factors of fracture, independent from BMD and reflecting the severity of Sa, should be considered when a preventive treatment of OP is planned <h3>Acknowledgements</h3> This study was supported by the GRIO "group de recherche et d'information de l'osteoporose". <h3>Disclosure of Interest</h3> None Declared
Abstract 4342: The allosteric Akt inhibitor MK-2206 inhibits neuroblastoma tumor cell growth in vitro and in vivo
Authors: Zhijie Li, Sridevi Ramalingam, Shuang Yan, Carol J. Thiele
Journal: Cancer Research (2011)

Abstract Background: Activated Akt in tumor tissue of NB patients is a marker of decreased event-free as well as overall survival. Our studies indicate activated Akt induces chemoresistance in NB cells and chemoresistance is a major problem in the treatment of Neuroblastoma (NB). The allosteric Akt inhibitor, MK-2206 inhibits the activation of the 3 Akt isoforms with IC50-Akt1 = 5.3nM, -Akt2 = 12nM and -Akt3 = 65nM. In this study we tested the effects of MK-2206 in vitro and in vivo pre-clinical models of NB. Methods: NB cell lines (NGP, SY5Y, KCNR, BE2, SKNFI, and AS) were treated with increasing concentrations of MK-2206 for 48 hours. MK-2206-induced cell death was evaluated by MTS assay. Phosphorylated Akt and its downstream target S6 were determined by Western Blot analysis. The effect of MK-2206 (100 or 200mg/kg/3 days/wk) on NB tumor growth was evaluated in a xenograft nude mouse model. Results: NB cell lines express all 3 Akt isoforms to varying levels. In in vitro studies, MK-2206 inhibited cell growth in all NB cell lines although with different sensitivities. The growth of NGP, SY5Y, KCNR and BE2 cells were more sensitive to MK-2206, with IC50&amp;lt;4μM; while the growth of AS and SKNFI were less sensitive, with IC50&amp;gt;11μM. MK-2206 treatment decreased phosphorylated-Akt and its target phosphorylated-S6 in NB cells to a comparable level in all tested cell lines regardless of biologic sensitivity to MK-2206. In in vivo studies, mice bearing the sensitive BE2 NB tumors were treated with MK-2206 (100 or 200mg/kg) while mice bearing the less sensitive AS tumors received MK-2206 (200mg/kg). There was an approx. 30% inhibition of tumor growth in each tumor model only in mice treated with 200mg/kg MK-2206 (P&amp;lt;0.01). MK-2206 (200mg/kg) treatment led to a comparable increase in survival in both models (P&amp;lt;0.01). Conclusion: This study indicates that despite differences in in vitro growth sensitivities, the Akt inhibitor, MK-2206 has a comparable anti-tumor cell growth inhibiting activity in vivo. This study supports the future evaluation of the combination of MK-2206 with chemotherapeutic drugs to improve the treatment efficacy in NB. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4342. doi:10.1158/1538-7445.AM2011-4342
M148 Investigating The Feasibility Of An Online Health Resource With Nurse Coaching To Support Self-management In Copd
Authors: J. Young, F. Early, S. Wisbauer, K. Homan, J. Fuld, L. Tojo
Journal: Thorax (2014)

<h3>Introduction</h3> Pulmonary rehabilitation includes self-management support for COPD but is not suitable for or accessible to all. Web based approaches have potential to provide self-management support but effectiveness is not consistently demonstrated and issues of reach and adoption are relatively unstudied. We performed a mixed methods before-and-after study of an intervention comprising web-based health promotion for LTC self-management, The Prevention Plan<sup>TM</sup> (TPP), with integrated nurse coach support. This report describes the qualitative evaluation. The aim was to understand the benefits gained and the characteristics of patients most likely to benefit. <h3>Method</h3> Nineteen patients were recruited in two waves from May 2012–January 2013. Key selection criteria included for group 1 FEV<sub>1</sub> &lt; 50% predicted and for group 2 FEV<sub>1</sub> &lt;75% predicted. Semi-structured interviews were scheduled for one month and three months after recruitment and were focused around experiences of the programme, benefits and self-management behaviours. Qualitative data were imported into NVivo 10 and analysed through thematic content analysis. Two researchers discussed the themes and subthemes to ensure non-redundant categorization. <h3>Results</h3> Fifteen patients were interviewed. Key benefits: increased motivation for self-management, use of self-management skills, increased access to resources and enhanced understanding of lifestyle risk factors. Benefits were facilitated by use of action plans within TPP, nurse coach support to on-going motivation and completion of a health risk assessment by those with little awareness of lifestyle risks. Barriers to gaining benefit included preference for one-to-one contact, insufficient tailoring of website content and difficulties with website navigation. Patients most likely to benefit were those who: wanted to change but had no behavioural strategy; had little previous disease education; had an autonomous sense of self-determination. <h3>Conclusions</h3> The programme provided good support for the action phase of behaviour change, but less so for the motivational phase. Patients who were ready to change but did not have knowledge, skills or strategies benefited the most. When implementing a behaviour change programme providers should identify whether it addresses motivation and/or behaviour and assess potential participants accordingly. People who are not ready or able to change may derive little benefit from a behavioural programme.
Treatment of Breast Cancer
Authors: Gabriel N. Hortobagyi
Journal: New England Journal of Medicine (1998)

Breast cancer is a major public health problem worldwide. Management of breast cancer was last reviewed in the Journal in 1992.1 The accumulation of new biologic information, the results of recent clinical trials, and the availability of new diagnostic and therapeutic tools make it appropriate to review the subject again.EpidemiologyThe incidence of breast cancer in the United States has been increasing gradually for the past three decades.2,3 It was estimated that 181,600 new cases of breast cancer were diagnosed in the United States in 1997 and that 44,190 people would die of breast cancer during the same . . .
Elevated F-18 FDG Uptake in the Psoas Muscle
Authors: SEIEI YASUDA, HIROFUMI FUJII, WAKOH TAKAHASHI, SHIGEHARU TAKAGI, MICHIRU IDE, AKIRA SHOHTSU
Journal: Clinical Nuclear Medicine (1998)

A 63-year-old man underwent a whole-body FDG PET study. On PET images, increased FDG uptake was noticed incidentally in the psoas muscles. The patient had exercised regularly every morning and night to prevent low back pain. The exercise routine was as follows: lying on his back with his hips and knees flexed and feet placed on the floor, he moved his knees together to the right and left repeatedly for 10 minutes. The psoas muscles, originating from the lumbar spine and inserting into the proximal portions of the femurs, were the target muscles in his exercise. Increased FDG uptake in these muscles was thought to be due to the effects of the exercise. It is not well understood how exercise training affects skeletal muscle glucose uptake. PET has been used in a growing number of situations, and this case suggests that PET could be used to investigate the effect of exercise on glucose metabolism in skeletal muscles.
846 CHARACTERIZATION OF THE EARLY VIRAL KINETICS IN COMPENSATED CIRRHOTIC TREATMENT-EXPERIENCED PATIENTS TREATED WITH BOCEPREVIR AND TELAPREVIR
Authors: C. Laouénan, J. Guedj, M. Lapalus, F. Khelifa-Mouri, M. Martinot- Peignoux, N. Boyer, L. Serfaty, J.-P. Bronowicki, F. Zoulim, F. Mentré, P. Marcellin
Journal: Journal of Hepatology (2013)
Learning from Our Errors
Authors: Jeremy Brown, Michael G. Worthington, Ellen S. Lathi
Journal: New England Journal of Medicine (1996)

A 50-year-old black man was brought to the emergency room. He had been unable to move his legs for four days and complained of impaired speech.The lesion in this patient may be in the lower-cranial-nerve area, perhaps due to a basilar meningitis, or somewhere in the cerebral hemispheres. I assume that it does not appear septic, because this was not described as his presenting picture. He appears to have a global process that is affecting his brain stem rather than higher cortical function, since he is not described as confused. What additional information do we have?Stage . . .
Triple HIV-1 Infection
Authors: Antoinette C. van der Kuyl, Karolina Kozaczynska, Remco van den Burg, Fokla Zorgdrager, Nicole Back, Suzanne Jurriaans, Ben Berkhout, Peter Reiss, Marion Cornelissen
Journal: New England Journal of Medicine (2005)

To the Editor: Dual infection with different strains of HIV type 1 (HIV-1) is reported with increasing frequency, attributed mostly to coinfection at the time of the primary infection. However, some patients were superinfected with a second virus after the original seroconversion,1 which generally accelerated disease progression.2 We encountered a case of serial HIV-1 superinfection resulting in a triple infection in a Dutch patient who was originally infected with a subtype B virus. A 35-year-old homosexual man was found to be HIV-1–seropositive in March 2001 and was referred for follow-up. Early in July 2003, the patient presented with acute onset . . .
Abstract 1015: Misaponin B induces G2-M arrest and autophagy via upregulation of miR1290 in non-small cell lung cancer (NSCLC) A549 cells
Authors: Gunho Won, Eun Jung Sohn, Myoung Seok Jeong, Sang Wook Yoon, Jihyun Lee, Bonglee Kim, Sung Hoon Kim
Journal: Cancer Research (2015)

Abstract Though Mi-saponin B is found to be the potent component among a mixture of saponins, its function still remains unlcear. Thus, in the present study, we investigated the anti-tumor mechanism of Mi-saponin B in non-small cell lung cancer (NSCLC) A549 cells. Mi-saponin B treatment caused cell growth inhibition via G2/M arrest in A549 cells. Moreover, Western blotting and qRT-PCR assays showed that Mi-saponin B induced conversion of LC3I to LC3II, a maker of autophagy. Immunofluorescence assay revealed that Mi-saponin B treatment formed the puncta of GFP-fused LC3II. Conversely, 3MA, an inhibitor of autophagy, attenuated the LC3II expression induced by Mi-saponin B in A549 cells. Also, transmission electron microscopy (TEM) showed that Mi-saponin B induces the autophagic vacuoles. Interestingly, miR1290 was upregulated in a dose dependent manner in Mi-saponin B treated A549 cells by qRT-PCR. Also, combined treatment of miR1290 and Mi-saponin B increased the expression of LC3II at protein and mRNA levels and also enhanced the formation of puncta of LC3II in A549 cells. Overall, our findings for the first time demonstrate that Mi-saponin B induces G2/M arrest and autophagy via upregulation of miR1290 in A549 cells as a potent anti-cancer agent. Citation Format: Gunho Won, Eun Jung Sohn, Myoung Seok Jeong, Sang Wook Yoon, Jihyun Lee, Bonglee Kim, Sung Hoon Kim. Misaponin B induces G2-M arrest and autophagy via upregulation of miR1290 in non-small cell lung cancer (NSCLC) A549 cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1015. doi:10.1158/1538-7445.AM2015-1015
ET-11 * RESVERATROL REGULATES GLIOBLASTOMA AND GLIOBLASTOMA STEM-LIKE CELLS VIA ANTI-TUMORIGENIC AKT DEPHOSPHORYLATION AND p53 ACTIVATION
Authors: P. Clark, S. Bhattacharya, P. van Ginkel, S. Darjatmoko, A. Elmayam, A. Polans, J. Kuo
Journal: Neuro-Oncology (2014)

Resveratrol (RES), a natural non-toxic plant product, exerts broad anti-cancer effects. RES was investigated for efficacy against glioblastoma (GBM) and therapeutically resistant GBM stem-like cells (GSC) hypothesized to drive tumor recurrence. Patient-derived GSC lines (12.1, 22, 33, 44) isolated via marker-neutral sphere cultures in stem cell medium, and U87 glioma were treated with RES. Low RES (25 µM) achieved significant inhibition of U87 cell proliferation after 4 days compared to control vehicle (DMSO) treatment. RES also inhibited GSC sphere-forming ability, with 50% inhibitory concentrations (IC50) from 5-25 µM. Interestingly, both 12.1 and 22 GSC lines highly express stem cell markers and initiate focal orthotopic GBM xenografts in brains of immunodeficient mice, and were most sensitive to RES compared to 33 and 44 GSC lines that cause highly infiltrative xenografts. This suggests differential RES response by various GBM/GSC subtypes. In a Matrigel transwell assay, 50 µM RES significantly inhibited invasion (>50%) of both U87 and 44 GSCs. RES also altered GSC progenitor marker expression, with 50 µM RES inducing increased expression of neural differentiation markers GFAP (astrocyte) and βIII-tubulin (neuron) after 3 days on western immunoblotting. We observed the broad anti-tumorigenic RES effects against GBM/GSC by dephosphorylating oncogenic AKT and activating tumor suppressor p53. Quantitative PCR revealed RES activates a large p53 tumor suppressive gene network (PIGG8, CD95, TP53, and NOXA). In U87 flank xenografts, oral RES (50 mg/kg daily) significantly inhibited xenograft growth, and single intra-tumoral 1mg injections reduced tumor volume by >60% compared to injection of vehicle control. In conclusion, RES causes broad anti-GBM and anti-GSC effects via AKT dephosphorylation and p53 activation, and warrants further study as a non-toxic adjuvant GBM therapy.
P793 VALIDATION OF FATTY LIVER INDEX FOR IDENTIFYING FATTY LIVER IN A LARGE-SCALE CROSS-SECTIONAL STUDY IN POPULATIONS SEEKING CHECK-UP IN TAIWAN
Authors: C.-W. Su, Y.-J. Wang, J.-C. Wu, T.-I. Huo, Y.-H. Huang, K.-C. Lee, H.-C. Lin, F.-Y. Lee, S.-D. Lee
Journal: Journal of Hepatology (2014)
Abstract 1477: Protein Tyrosine Kinase 6 promotes peripheral adhesion complex formation, cell migration, and the epithelial mesenchymal transition in prostate cancer.
Authors: Angela L. Tyner, Yu Zheng
Journal: Cancer Research (2013)

Abstract Protein tyrosine kinase 6 (PTK6) is an intracellular tyrosine kinase that is evolutionarily related to Src kinases. In the normal prostate, total and active PTK6 is localized within the nucleus, but nuclear localization is lost in prostate tumors. While the majority of total PTK6 is localized within the cytoplasm of PC3 cells, a human prostate cancer cell line, the active pool of PTK6 that is phosphorylated on tyrosine residue 342 is membrane associated. Ectopic expression of membrane targeted PTK6 leads to enhanced activation of PTK6 at the membrane and formation of peripheral adhesion complexes and increased migration of PC3 cells. Ectopic expression of PTK6 in SYF cells, a nontransformed mouse embryonic fibroblast cell line lacking Src, Yes, and Fyn kinases leads to cell transformation and tumor growth in vivo. Ectopic expression of active membrane-targeted PTK6 in PC3 cells promotes the epithelial mesenchymal transition (EMT). PTK6 regulates the EMT through AKT, as knockdown of AKT or inhibition of AKT activity by knockdown of p130CAS partially rescues the phenotype. PC3 cells expressing active membrane targeted PTK6 exhibit increased migration in vitro and form more metastases in a xenograft mouse model, while knockdown of PTK6 promotes an epithelial phenotype and impairs tumorigenesis in vivo. In prostates of Probasin-Cre, Pten flox/flox mice, striking activation of endogenous mouse PTK6 is observed at the membrane in Pten-null prostates, and this is accompanied by deregulated expression of E-cadherin and vimentin. We found a reverse correlation between PTK6 and E-cadherin expression in normal and metastatic human prostate cancer samples, and show PTK6 is activated at the membrane in some high-grade prostate tumors. Our studies reveal novel functions for PTK6 in prostate cancer, and define it as a potential therapeutic target. Citation Format: Angela L. Tyner, Yu Zheng. Protein Tyrosine Kinase 6 promotes peripheral adhesion complex formation, cell migration, and the epithelial mesenchymal transition in prostate cancer. [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 1477. doi:10.1158/1538-7445.AM2013-1477
Achalasia with Megaesophagus
Authors: Chinemerem Okwara, David Cangemi
Journal: New England Journal of Medicine (2015)

A 63-year-old man with a history of hypothyroidism presented with a 10-year history of dysphagia to solid foods and liquids. He had had worsening of his symptoms for 6 months before presentation, with an associated weight loss of 27 kg.
Case 35-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Sergio J. Cervi-Skinner, Benjamin Castleman
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 20-year-old man was admitted to the hospital because of thyroid nodules.At the age of nine years he was told of a heart murmur. He was well until one year before admission, when he began to experience brief episodes of palpitation. Three months before entry he consulted a physician, who told him that he had a thyroid nodule and referred him to this hospital. There was no history of hypertension, headache, flushing, diarrhea, nephrolithiasis or constipation.A brother, aged 25 years, had undergone excision of a pheochromocytoma and had had multifocal medullary carcinoma of the thyroid . . .