tbuckley/cabot-search huggingface dataset:
Abstract 5179: Inflammatory breast cancer cell motility: Understanding the role of E-cadherin and gli1 in IBC migration and the development of a novel high content assay to assess cell migration
Authors: Zainab Thomas, Jonathan Z. Sexton, Gayathri R. Devi, Kevin P. Williams
Journal: Cancer Research (2010)

Abstract Inflammatory Breast Cancer (IBC) is a highly aggressive subtype of breast cancer and is now regarded as clinicopathologically distinct from neglected locally advanced breast cancer (LABC). In addition, African-Americans, native Americans and younger women are disproportionately affected with IBC having the worse survival. The molecular mechanisms underlying the invasiveness of IBC are not clear. Interestingly, upregulation of the integral membrane protein E-cadherin is the marker reported to be seen most consistently in IBC. In contrast to IBC, E-cadherin is typically reduced in most cancers and the subsequent loss in cell-cell adhesion results in the rapid progression to an invasive and metastatic phenotype. Inactivation of the E-cadherin cell adhesion system can occur by a number of genetic and epigenetic mechanisms. Gli1, the main transcriptional activator of hedgehog signaling, can promote loss of E-cadherin. Gli1 induces expression of Snail which is then found to downregulate E-cadherin expression. In an IBC cellular model, SUM149, we have identified elevated levels of Gli1. Further, inhibition of Gli1 using siRNA caused apoptosis in these cells. We hypothesize that the invasiveness of IBC cells is modulated in part by a connection between E-cadherin and Gli1 levels in IBC and that modulating this pathway will lead to changes in IBC cell motility. This project has two main objectives: 1), Investigate the expression levels of E-cadherin and Gli1 in IBC cells and their roles in IBC motility, and 2), Develop and validate a high content microscope-based assay for measuring motility of IBC cells. Cell motility assays were performed in six-well plates with Gli1 siRNA treated SUM149 cells that resulted in reduced motility and viability of these cells compared to control siRNA treated cells. These results suggest that targeting Gli1 can reduce IBC's invasiveness. This pathway provides opportunities for identifying molecules that might affect tumor invasiveness. We have also developed a novel live cell high content phenotypic screen for modulators of IBC cell motility that may potentially lead to new therapeutics for IBC. An understanding of how any of these molecules affect the Gli-Snail-E-cadherin system would provide useful tools for better probing the role of this pathway in IBC. Furthermore, the high content migration phenotypic assay should be generally applicable to investigating a range of invasive cancer types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5179.
The psychiatrist's role in aerospace operations
Authors: W H Sledge, J A Boydstun
Journal: American Journal of Psychiatry (1980)

This paper presents two unique aspects of aerospace psychiatry: the influence of the specialized stressors and occupational requirements of an aviation career and the ambiguous role of the aerospace psychiatrist. Aerospace psychiatrists have multiple, sometimes conflicting, responsibilities to the organization and society (the social control task) and to the individual aviator (the humanistic and medical tasks). In the two case reports below the authors describe airmen who had vasovagal syncope and how the psychiatrist intervened and resolved these conflicting tasks.
AB0104 Modulation of immunity through cigarette smoke induced changes in dendritic cell functions - potential relevance to autoimmunity
Authors: R. Vassallo, P. Walters, V. Taneja
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Epidemiological studies implicate cigarette smoking as a major risk factor predisposing to the development of seropositive rheumatoid arthritis (RA). The mechanisms by which cigarette smoking promotes RA are largely unknown, but likely involve modulation of dendritic cell (DC) functions. <h3>Objectives</h3> To determine mechanisms by which cigarette smoke modulates DC functions thereby potentially modulating antigen presentation and promoting autoimmunity. <h3>Methods</h3> C57B6 mice were placed in a TE-2 smoking chamber and chronically exposed to cigarette smoke generated from Kentucky 3R4F research cigarettes. Murine DCs were extracted from the spleen and lymph nodes at the time of sacrifice, and analyzed for viability, T cell proliferative potential, and cytokine/chemokine secretion. Bone marrow DCs were stimulated with lipopolysaccharide in the presence or absence of cigarette smoke extract and microarray analysis performed to determine alternations in gene expression induced by cigarette smoke. <h3>Results</h3> DCs extracted from cigarette smoke exposed mice demonstrated enhanced viability and minor alteration in costimulatory molecule expression. DC-mediated allo-proliferative T cell responses were not significantly different between cigarette smoke exposed and control DCs. LPS-activated DC extracted from cigarette smoke exposed mice produced lower amounts of interleukin-12, but produced greater amounts of TNF-alpha, PGE2, and neutrophilic chemokines. Gene array analysis of DCs incubated with cigarette smoke extract during activation with LPS showed augmentation and suppression of a large number of genes associated with cellular toxicity, oxidative stress, and immune regulation. <h3>Conclusions</h3> Cigarette smoke exposure modifies murine DC functions in profound ways. The effect of smoking on host DC function is complex and both stimulatory and suppressive effects occur. The determination of specific cigarette smoke induced effects on DC functions, and the determination of cigarette smoke effects on antigen-specific immunity, particularly in the context of specific host genetic traits, are essential future studies needed to clarify specific mechanisms by which smoking promotes seropositive RA. <h3>Disclosure of Interest</h3> None Declared
P379Slowed conduction velocity in spontaneously hypertensive rat hearts is due to disease related remodelling
Authors: S Alayoubi, S Al-Aidarous, C Pinto Ricardo, P Dias, J Zaman, C Kane, P Camelliti, N Peters, M Yacoub, C Terracciano
Journal: Cardiovascular Research (2014)

The spontaneously hypertensive rat (SHR) is a well-characterised model for studies of hypertension and atrial arrhythmias but little is known about the electrophysiological properties of the left ventricle (LV) and their relation with ventricular arrhythmias in the development of this disease. To investigate the mechanisms behind electrophysiological abnormalities in the LV we used myocardial slices which allow the investigation of functional and structural properties in the same tissue location. Myocardial slices (300μm thick) were prepared from young (3months) and old (20months) SHR and age-matched control LVs. Slices were point-stimulated and analysed using a multi-electrode array system; longitudinal conduction velocity (CVL) was measured. CVL was unchanged between the young and old control groups. However, CVL was significantly reduced in the old SHR group compared to the corresponding age-matched control and young SHR groups (20months: 27±2 cm/s, n=29 slices/3 hearts vs control 39±4 cm/s, n=22 slices/4hearts and 3months: 37±3 cm/s, n=18 slices/3 hearts; p<0.05). In support of the slower CVL found in the aged group, western blotting analysis revealed a reduction in the expression of the gap junctional protein connexin43 in the old SHR when compared to age-matched control (in arbitrary units; control: 2±0.2,n=8slices /4hearts SHR:1.2±0.1,n=6slices/3hearts; p<0.01). These findings suggest that LV electrophysiological abnormalities are a result of disease progression as opposed to age-related changes.
Abstract 763: Hyperthermia promotes c-myc turnover and reduces ODC expression in colorectal cancer cells.
Authors: Christina T.K. Wales, Aaron T. Jacobs
Journal: Cancer Research (2013)

Abstract Hyperthermia therapy is an FDA-approved procedure that is used to improve the clinical response to radiation and chemotherapy in a variety of solid malignancies. This method involves raising the temperature of tumor-bearing tissues to 41-43°C, which is commonly achieved by using microwave or radiofrequency (RF)-emitting devices. Despite a multitude of treatment centers that are now providing this type of therapy, the cellular and molecular processes are not fully understood. Here, we report that that the oncogenic transcription factor, c-myc has a potentially important role in the anti-cancer mechanism of hyperthermia. By treating colorectal cancer cells (RKO cell line) with heat (incubation at 42°C), we observe a rapid decrease in c-myc levels that is not seen with other transcription factors. We have also observed a similar effect in other cell types, including lung (A549) and neuroblastoma (SH-SY5Y). It is already known that the turnover of c-myc protein is enhanced by phosphorylation at Thr58. Our Western blot data reveal that hyperthermia causes a significant increase in Thr58 phosphorylation, which is accompanied by a reduction in total c-myc levels. c-Myc is frequently deregulated in human cancers, where it promotes the expression of genes that drive tumor cell proliferation. To assess the role of c-myc target genes in the response to hyperthermia, we looked at one such target gene, ornithine decarboxylase (ODC), which catalyzes the rate-limiting step in polyamine biosynthesis. We see that the hyperthermia-induced degradation of c-myc is accompanied by a drastic reduction in ODC mRNA and protein levels. Using actinomycin D, we observe that heat has no effect on ODC mRNA stability, suggesting that the decrease in ODC is due to a reduction in gene transcription. In support of this, we find that silencing c-myc expression with siRNA inhibits ODC mRNA and protein levels by a similar amount as hyperthermia. We propose that the down-regulation of ODC caused by c-myc degradation may be an important part of the clinical response to hyperthermia, and future work will evaluate the effect of heat on cellular polyamine levels. Citation Format: Christina T.K. Wales, Aaron T. Jacobs. Hyperthermia promotes c-myc turnover and reduces ODC expression in colorectal cancer cells. [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 763. doi:10.1158/1538-7445.AM2013-763
Abstract P5-01-04: Preoperative PET-CT Staging of Axillary Node Positive Breast Cancer
Authors: NM Ni Mhuircheartaigh, M Kell, FL Flanagan, GC Hargaden, HM Fenlon, TF Gorey, M Stokes, RR Salman, CS. Smith
Journal: Cancer Research (2010)

Abstract Purpose: 18F-FDG PET CT is a powerful diagnostic tool, which has enhanced systemic staging in oncology. Our aim was to evaluate the utility of performing staging PET-CT on patients with biopsy proven metastatic axillary lymph nodes that had clinically occult distant metastatic disease and to assess any change in management arising from it. Materials &amp; Methods: All patients with newly diagnosed breast cancer undergo axillary ultrasound and cytology of suspicious lymph nodes, and those with positive cytology undergo pre operative PET-CT. Nodes were classified on ultrasound according to assessment categories R1-R5. PET-CT images were acquired with a Siemens Biograph High Resolution 16 slice PET/CT scanner using full dose CT and intravenous contrast. Results: Eighty two patients were identified with positive axillary cytology following ultrasound biopsy and underwent PET-CT; 28/82 patients (34%) had extra axillary disease. In total 30 patients (37%) had a change in management due to the PET-CT findings. 2 patients had more extensive surgery than previously planned, 7 patients (8%) had an extended radiation field and 21 patients (26%) were treated for distant metastases. Discussion: The detection of metastatic disease beyond the axilla has important implications for treatment options and survival. We detected clinically overt metastatic disease beyond the axilla and altered management in 37% patients due to the PET/CT findings. On this basis we recommend PET-CT for this preoperative cohort of patients with node positive breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-04.
Gratitude, Memories, and Meaning in Medicine
Authors: Hasan Bazari
Journal: New England Journal of Medicine (2010)

The card, with its picture of a bouquet of flowers, was on my desk when I arrived at the hospital on Monday morning. I opened it, assuming it was a thank-you note from an interviewee for our residency program. But the handwriting was that of an elderly person who had taken the pains to write, with slants and slopes necessitated by decreased mobility. Under the printed lines, “A little ray to brighten your day. Thinking of you,” the sender had written, “My mother, Mary Louise Kelly, '83–'84, would be pleased with your role at MGH. Please remember to wear a . . .
Data Sharing and the<i>Journal</i>
Authors: Jeffrey M. Drazen
Journal: New England Journal of Medicine (2016)

We want to clarify, given recent concern about our policy, that the Journal is committed to data sharing in the setting of clinical trials. As stated in the Institute of Medicine report from the committee1 on which I served and the recent editorial by the International Committee of Medical Journal Editors (ICMJE),2 we believe there is a moral obligation to the people who volunteer to participate in these trials to ensure that their data are widely and responsibly used. Journal policy will therefore follow that outlined in the ICMJE editorial and the IOM report: when appropriate systems are in place, . . .
SAT0497 Effect of Raloxifene on Osteoporosis and Disease Activity in Postmenopausal Female with Rheumatic Diseases
Authors: W.S. Lee, I.-S. Min, Y.-J. Choi, C.-H. Lee, M.-S. Lee, W.-H. Yoo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To study the efficacy of raloxifene on disease activity and bone mineral density (BMD) in postmenopausal women with rheumatic diseases receiving long-term glucocorticoids (GC). <h3>Methods</h3> Postmenopausal women with rheumatic diseases and osteoporosis were included. Patients with a history of thromboembolism or antiphospholipid antibody positivity were excluded. They were managed with raloxifene (60 mg/day) plus elemental calcium (1,200 mg/day). BMD of the hip and spine was measured initially and at month 12, and disease activity was serially assessed using SLEDAI and DAS28. <h3>Results</h3> The study group comprised 130 patients (81 rheumatoid arthritis, 7 lupus, 15 Sjogren9s syndrome, 11 scleroderma, 11 Behcet9s disease and 5 other rheumatic diseases, 86 assigned to receive GC and 44 patients not receiving GC, mean ± SD age 60.1±9.0 vs. 59.3±7.0 years). Demographic data, osteoporotic risk factors and BMD at various sites were similar between the two groups of patients. The duration and dose of prednisolone received was 72.5±24 months and 3.3±1.6 mg/day. At month 12, a significant gain in the lumbar spine (+0.9±0.7%; p=0.04 vs. +0.4±0.1%; p=0.05) and total hip BMD (+1.1±0.5%; p=0.03vs. 1.5±0.7%; p=0.04) was observed in patients receiving GC or not. However, femoral neck BMD was decreased in both groups. No patient had a major flare of lupus and rheumatoid arthritis. No fracture and thromboembolic events were reported. <h3>Conclusions</h3> Raloxifene was well tolerated in postmenopausal female patients with rheumatic diseases who had inactive disease and in whom hypercoagulability was not identified. Raloxifene increased total hip and lumbar spinal BMD in patients receiving corticosteroids or not. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5035
PRESERVED MYOCARDIAL METABOLIC EFFICIENCY IN EXERCISE-INDUCED LEFT VENTRICULAR HYPERTROPHY
Authors: Meagan Murphy Wasfy, James R. DeLuca, Courtney Foster, Rory Weiner, Gregory Lewis, Adolph Hutter, Michael Picard, Marcelo Di Carli, Aaron Baggish
Journal: Journal of the American College of Cardiology (2016)
Reverse of the Differential Uptake Intensity of Tc-99m MIBI and Tc-99m V-DMSA By Multiple Myeloma Lesions in Response to Therapy
Authors: T Athanasoulis, J Koutsikos, L A Moulopoulos, S Tsiouris, M A Dimopoulos, C Zerva
Journal: Clinical Nuclear Medicine (2003)

Purpose The objective of this study was to compare the uptake changes of Tc-99m 2-methoxy isobutyl isonitrile (MIBI) and Tc-99m pentavalent dimercaptosuccinic acid (V-DMSA) in multiple myeloma (MM) lesions in response to high-dose chemotherapy (HDC). Materials and Methods The authors compared Tc-99m MIBI and Tc-99m V-DMSA scans before and after HDC in a patient with focal MM lesions without amyloidosis who had received previous standard chemotherapy as well. Results HDC had the effect of eliminating all Tc-99m MIBI uptake in the lesions. Tc-99m V-DMSA uptake was increased in lesions presenting significant initial Tc-99m MIBI uptake. In 1 particular lesion that demonstrated this phenomenon, magnetic resonance showed necrosis of the area of MM. Conclusion The authors consider that the effect of increasing Tc-99m V-DMSA uptake in the absence of an increase in viable plasma cells possibly reflects the treatment-generated inflammatory and fibrotic changes and not necessarily viable tumor tissue. Exclusive focal Tc-99m V-DMSA uptake in this clinical setting could be considered as a sign of effectively treated lesions and not a sign of deterioration.
Comment on: Acute and chronic hepatitis E virus infection in human immunodeficiency virus‐infected U.S. women
Authors: Lisa A Spacek, Steven F. Solga
Journal: Hepatology (2016)

We commend Kuniholm et al.1 for their important work on the prevalence of hepatitis E (HEV)/human immunodeficiency virus (HIV) coinfection in U.S. populations based on a large sample of subjects from the Women's Interagency HIV Study (WIHS)/Multicenter AIDS Cohort Study (MACS). We are concerned, however, about the generalizability of their results. Specifically, their conclusion that "the rarity of HEV viremia in the WIHS/MACS study populations suggests that widespread screening for HEV in HIV+ U.S. populations is not warranted" may not be applicable to the broader U.S. HIV population. As noted by the researchers, "direct contact with or consumption of pigs, wild boar, and deer (and possibly other mammals)" is the primary known risk factor for HEV genotypes 3 and 4. However, all 10 WIHS/MACS centers are urban based, with two apiece from our nation's largest cities (New York, Los Angeles, and Chicago). Additionally, 89% of this cohort were female, but males are significantly more likely to harvest and consume game meat.2 Having provided HIV and hepatology patient care in both Baltimore and Pennsylvania (a state with a large rural hunting population), we are routinely reminded of the many demographic differences among these populations. And though data regarding geographical risk are conflicting,3, 4 based on our experience it is unsurprising that the only other U.S. case of chronic HEV cited by the authors resides in Pennsylvania.5 In conclusion, Kuniholm et al. present essential data that are an important milestone in HEV/HIV research. However, because the researchers did not sufficiently acknowledge these limitations, clinicians may be misled about the risk of HEV. A greater research effort is needed to include broader geographical diversity, especially for HIV+ patients residing in nonurban areas. Lisa A Spacek, M.D., Ph.D.1 Steven F. Solga, M.D.2 1School of Medicine Johns Hopkins University Baltimore, MD 2St. Luke's University Hospital Bethlehem, PA
Effect of Cigarette Smoking on Gastric Secretions of Patients with Duodenal Ulcer
Authors: Philip Cooper, James B. Knight
Journal: New England Journal of Medicine (1956)

MANY clinical opinions on the effect of smoking on gastric secretions have been expressed, but a careful review of the literature fails to reveal any studies sufficiently detailed or adequately controlled to substantiate such opinions scientifically.Haag1 believed that the effects of smoking on the gastrointestinal tract were variable, depending on which of the autonomie ganglionic systems was more stimulated.Gray2 reported that 50 of 63 patients with duodenal ulcer showed an increase in the volume of gastric secretion after smoking, and a fourth of the patients showed a concomitant rise of gastric acidity. Schnedorf and Ivy3 found that gastric . . .
Dysphagia and Hypertrophic Spurring of the Cervical Spine
Authors: David A. Hilding, Muiran O. Tachdjian
Journal: New England Journal of Medicine (1960)

ASYMPTOMATIC hypertrophic spurs of the anterior margin of the cervical vertebras are not uncommon. However, if the mass of hypertrophic bone projects into the pharynx enough to impinge upon the food passageway, it can mechanically interfere with deglutition. Pain or difficulty in swallowing, foreign-body sensation, lump in the throat and a constant urge to clear the throat are symptoms attributed to this condition.In 1926 Mosher1 described difficulty in swallowing caused by exostoses of the cervical vertebras. In addition to his 2 cases 34 have been reported.2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Surgical excision of the osteophyte was performed on 4 patients.6 , 7 , 15 , 16 The purpose of . . .
An unusual finding at screening colonoscopy: polypoid follicular lymphoma with marginal zone differentiation
Authors: E. Despott, P. Tadrous, K. Naresh, A. Savio, M. Marshall, B. Saunders
Journal: Endoscopy (2011)

An asymptomatic 60-year-old man underwent screening colonoscopy after positive fecal occult blood testing (FOBT) during participation in the UK national bowel cancer screening program. Colonoscopy revealed clusters of sessile polypoid masses involving the rectum, sigmoid colon, cecum, and terminal ileum ([Fig. 1], [Video 1]).
Transient parotitis after upper gastrointestinal endoscopy
Authors: S. Vadivel Kumaran, B. Sumathi, D. Nirmala Natarajan
Journal: Endoscopy (2013)

A 12-year-old boy with epilepsy was referred for recurrent abdominal pain of 2 months duration and underwent endoscopy without conscious sedation. The patient strained a little during the procedure and antral gastritis was detected. After 2 minutes of having the procedure, he developed swelling of the right parotid gland ([Fig. 1]). On examination, he had bilateral nontender, noncrepitant parotid enlargement without excess salivation, and gingival hyperplasia (phenytoin-induced) but was otherwise clinically normal. Ultrasound showed an edematous right parotid gland ([Fig. 2]); the left parotid was normal and the swelling on the right side subsided within 30 minutes.