tbuckley/cabot-search huggingface dataset:
Abstract 4249: Shape change induces nitric oxide and stemness in colorectal cancer cells
Authors: J. Milburn Jessup, Snorri S. Thorgeirsson, Louis A. Espinoza
Journal: Cancer Research (2010)

Abstract Shape changes in cancer cells profoundly alter the expression of genes that affect malignant properties. We postulated that shape change may increase expression of NANOG, an embryonic stem cell transcription factor expressed in human colorectal carcinoma (CRC) that regulates pluripotency and proliferation. Since shape change also increases intracellular nitric oxide (iNO) expression, we further postulated that iNO modulates NANOG expression. Clone A and CX-1 human CRC lines were cultured in serum-containing medium in monolayer cultures or in spheroids in serum free medium in low attachment plates. NANOG promoter activity was assessed in stable transfectants expressing promoter-driven GFP. iNO concentrations were determined by fluorescence cytometry with DAF-FM diacetate while Nanog gene and protein expression was analyzed by qRT-PCR and densitometry of western blots, respectively. Spherogenicity was measured by the percentage of spheroids formed from single cells in serum-free medium. Monolayer cultures with flat, spreading cells had low NANOG gene and protein expression, promoter activity and iNO whereas spheroids displayed high NANOG gene expression, promoter activity and iNO. 7 day monolayer cultures initiated with 104 cells/ml (Sparse) grew horizontally compared to cultures initiated with 106 cells/ml (Dense) that grew vertically and formed colonies. Sparse cultures had low NANOG gene expression, low NANOG promoter activity and low iNO. Dense cultures had high NANOG gene expression, NANOG promoter activity and iNO. Since NO stimulates cGMP production, the effects of the NO synthase inhibitor L-NMMA, NOC (a NO donor), 8-Br-cGMP (cGMP agonist) and ODQ (cGMP inhibitor) were tested on CRC monolayers. Physiologic concentrations of NOC increased NANOG and Oct4 gene and protein expression 3-fold in highly metastatic CX-1 cells but not in weakly metastatic Clone A cells. NOC also increased CD44 in CX-1 but not Clone A. cGMP may regulate NANOG expression since 8-Br-cGMP increased NANOG and Oct4 protein expression up to 3-fold in CX-1 but not in Clone A and without affecting CD44 expression. ODQ inhibited NANOG expression. L-NMMA stimulated both NANOG protein expression and the spherogenicity of CX-1 but not Clone A. NOC and 8-Br-cGMP increased inducible NO synthase (NOS2) but not NOS3 gene expression 3-fold in both spheroids and monolayers while ODQ decreased NOS2 levels. Assays are in progress to test the effects of NOC and the cGMP modulators on spherogenicity. Shape change, iNO and cGMP enhance NANOG, NOS2 and CD44 expression to alter CRC cancer stem cell function. cGMP may be an important regulator of stemness genes. 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 4249.
Melanoma survival in the United States, 1992 to 2005
Authors: Lori A. Pollack, Jun Li, Zahava Berkowitz, Hannah K. Weir, Xiao-Cheng Wu, Umed A. Ajani, Donatus U. Ekwueme, Chunyu Li, Brian P. Pollack
Journal: Journal of the American Academy of Dermatology (2011)

Population-based data on melanoma survival are important for understanding the impact of demographic and clinical factors on prognosis.We describe melanoma survival by age, sex, race/ethnicity, stage, depth, histology, and site.Using Surveillance, Epidemiology, and End Results data, we calculated unadjusted cause-specific survival up to 10 years from diagnosis for 68,495 first primary cases of melanoma diagnosed from 1992 to 2005. Cox multivariate analysis was performed for 5-year survival. Data from 1992 to 2001 were divided into 3 time periods to compare stage distribution and differences in stage-specific 5-year survival over time.Melanomas that had metastasized (distant stage) or were thicker than 4.00 mm had a poor prognosis (5-year survival: 15.7% and 56.6%). The 5-year survival for men was 86.8% and for persons given the diagnosis at age 65 years or older was 83.2%, varying by stage at diagnosis. Scalp/neck melanoma had lower 5-year survival (82.6%) than other anatomic sites; unspecified/overlapping lesions had the least favorable prognosis (41.5%). Nodular and acral lentiginous melanomas had the poorest 5-year survival among histologic subtypes (69.4% and 81.2%, respectively). Survival differences by race/ethnicity were observed in the unadjusted survival, but nonsignificant in the multivariate analysis. Overall 5-year melanoma survival increased from 87.7% to 90.1% for melanomas diagnosed in 1992 through 1995 compared with 1999 through 2001, and this change was not clearly associated with a shift toward localized diagnosis.Prognostic factors included in revised melanoma staging guidelines were not available for all study years and were not examined.Poorer survival from melanoma was observed among those given the diagnosis at late stage and older age. Improvements in survival over time have been minimal. Although newly available therapies may impact survival, prevention and early detection are relevant to melanoma-specific survival.
724 Gene expression in hepatic and white adipose tissues of patients with obesity-related non-alcoholic steatohepatitis (NASH)
Authors: R. Collantes, A. Baranova, K. Schlauch, S. Gowder, L. Del Giacco, H. Elarinyl, A. Van Meter, A. Afendy, J.E. Ong, Z. Goodman, V. Chandhoke, Z.M. Younossi
Journal: Journal of Hepatology (2006)
Book: Home Sweet Home? The Impact of Poor Housing on Health
Authors: S. Nettleton
Journal: BMJ (2000)

Alex Marsh, David Gordon, Christina Pantazis, Pauline Heslop Policy Press, £16.99, pp 90 ISBN 1 86 134 176 8 Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> “The impact of multiple housing deprivation would appear to be the same order of magnitude as addressing the issue of smoking and the risk to health posed by multiple housing deprivation seems to be, on average, greater than that posed by excessive alcohol consumption.” Furthermore, “housing history matters,” as adults who are currently living in good housing circumstances are more likely to be ill if they experienced adverse housing conditions earlier in life. These represent some of the key findings of this study, which are particularly important within the context … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
The Injured Cervical Spine
Authors: Donald J. Prolo
Journal: JAMA (1973)

Optimal management of cervical spine injuries requires immediate immobilization, then reduction, stabilization, early ambulation, and decreased time in bed. The halo skeletal fixation instrument provides a convenient means of exerting immediate traction in the acute stage and skeletal fixation during the chronic stage while bony repair and union are occurring. It offers numerous advantages over the more traditional skull tong traction and extended bed rest, the most salient of which are patient comfort and safety. Its application and maintenance are simple, complications of its use are infrequent and minor, and hospitalization time is markedly reduced.
Increased interleukin‐10 and macrophage inflammatoryprotein‐1α release from blood monocytes <i>ex vivo</i> duringlate‐phase response to allergen in asthma
Authors: S. Lim, M. John, J. Seybold, D. Taylor, C. Witt, P. J. Barnes, K. F. Chung
Journal: Allergy (2000)

We determined the effect of late-phase responses to allergen challenge of mildly allergic asthmatic patients on the expression and release of the cytokines IL-10 and MIP-1alpha from peripheral blood monocytes.Sixteen mildly allergic asthmatics were exposed to increasing concentrations of allergen aerosol. Nine demonstrated an early response alone (single responders), while seven had an early followed by a late response (dual responders). Monocytes were isolated from venous blood before and 24 h after allergen challenge, and placed in short-term culture for determination of IL-10 mRNA expression by reverse-transcription polymerase chain reaction and protein release. MIP-1alpha protein release was measured by radioimmunoassay.IL-10 mRNA expression was significantly higher in dual responders than early responders alone, for unstimulated monocytes or for monocytes exposed to lipopolysaccharide or IL-1beta. In addition, the release of IL-10 and MIP-1alpha from monocytes of dual responders was also enhanced.Circulating monocytes are primed to release more of the cytokines, IL-10 and MIP-1alpha, in dual but not in single responders, at 24 h after allergen. They may contribute to allergen-induced inflammatory responses in the airways.
Health journalism: two clicks away from Britney Spears?
Authors: R. Coombes
Journal: BMJ (2009)

SNX-482, a peptide toxin isolated from tarantula venom, has become widely used as an inhibitor of Cav2.3 voltage-gated calcium channels. Unexpectedly, we found that SNX-482 dramatically reduced the A-type potassium current in acutely dissociated dopamine neurons from mouse substantia nigra pars compacta. The inhibition persisted when calcium was replaced by cobalt, showing that it was not secondary to a reduction of calcium influx. Currents from cloned Kv4.3 channels expressed in HEK-293 cells were inhibited by SNX-482 with an IC<sub>50</sub> of &lt;3 nm, revealing substantially greater potency than for SNX-482 inhibition of Cav2.3 channels (IC<sub>50</sub> 20–60 nm). At sub-saturating concentrations, SNX-482 produced a depolarizing shift in the voltage dependence of activation of Kv4.3 channels and slowed activation kinetics. Similar effects were seen on gating of cloned Kv4.2 channels, but the inhibition was less pronounced and required higher toxin concentrations. These results reveal SNX-482 as the most potent inhibitor of Kv4.3 channels yet identified. Because of the effects on both Kv4.3 and Kv4.2 channels, caution is needed when interpreting the effects of SNX-482 on cells and circuits where these channels are present.
HFE gene mutations and alcohol intake are main determinants of liver iron overload in male patients with chronic viral hepatitis
Authors: A. Vergani, M. Viganò, I. Malosio, L. Fossati, C. Arosio, P. Trombini, A. Ricci, G. Bovo, G. Boari, A. Piperno
Journal: Journal of Hepatology (1998)
NONSURGICAL BILIARY TRACT DRAINAGE
Authors: George M. Niles
Journal: JAMA (1927)

To the Editor:  —The article of Dr. C. L. Hartsock of Cleveland on migraine (The Journal, Oct. 29, 1927) was of interest, especially the paragraph mentioning the efficacy of nonsurgical biliary tract drainage in cases presenting symptoms of biliary and duodenal stasis.  During the last six years I have treated forty-eight persons suffering from migraine, or so so-called bilious headaches. Four of these had had the gallbladder surgically drained, and two the gallbladder removed. All had suffered for ten or more years, and about half were unable to pursue a gainful occupation. These patients had run the gamut of medical therapeutics, with only temporary relief. All were given nonsurgical biliary tract drainage, generally at frequent intervals at first, and then at longer intervals. None were encouraged to expect favorable results under ten drainages; in fact, some of them have taken as many as seventy-five. These patients have had all intercurrent
George Harold Godwin Chase
Authors: D. Chase
Journal: BMJ (2003)

Former general practitioner Stamford, Lincolnshire (b Chesterfield 1914; q Guy's Hospital, London, 1936), died from renal failure on 15 February 2003.​2003.




Figure 1




After a brief spell in practice in Newark, in 1943 Harold moved to Stamford, where he worked until retirement in 1976. He was always involved in sport, gaining a half blue for fives at Cambridge, and later in Stamford captaining a cricket club and establishing a squash club. He leaves a wife, Peggy; three children; and eight grandchildren.
Predictive value of oesophageal pH variables in children with gastro-oesophageal reflux.
Authors: D J Colson, C A Campbell, V A Wright, B W Watson
Journal: Gut (1990)

Sixty three 24 hour oesophageal pH studies were performed in children with known or suspected gastro-oesophageal reflux and their progress was followed for at least a year. Forty two studies were of children who were well at follow up who were not receiving medical treatment for gastro-oesophageal reflux, and had not required antireflux surgery. Twenty one studies were from children who were still on treatment for gastro-oesophageal reflux or had undergone antireflux surgery. The results were analysed using non-parametric statistics to assess the value of pH recordings in predicting which children were likely to have continuing problems. Sleep reflux (minutes/hour) and acid clearing time were the most highly significant variables (p less than 0.0005 and p less than 0.0001 respectively). The results suggest that either sleep gastro-oesophageal reflux of more than 6.4 minutes/hour or an acid clearing time of seven minutes or more are good predictors of the clinical outcome (specificity 88.1%, sensitivity 81.0%). Three of the five children with false positive results were under 10 months of age. Positive results in this age group should therefore be interpreted with caution.
Interactions Between Rhinovirus-Induced IFN-alpha Production at Birth and the Severity of Rhinovirus Illnesses in the First Year of Life
Authors: D.F.G. DaSilva, C.J. Tisler, T.E. Pappas, M.D. Evans, K.T. Sullivan Dillie, K.A. Roberg, E.L. Anderson, L.E.P. Salazar, R.A. Grabher, K.M. Hanson, R.E. Gangnon, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2007)
The Long-Term Effects of Force-transmission in an Injured Wrist, Measured With Dual-Energy X-ray Absorphometry
Authors: MAARTEN M. HOOGBERGEN, WILLEM RIJNDERS, ALICE J. VAN DONGEN, PETER C. ANEMA, PETER P. VAN RIJK, PAUL H. M. SPAUWEN, JOHN M. G. KAUER
Journal: Clinical Nuclear Medicine (2000)

Purpose To investigate the feasibility of using a dual-energy X-ray absorphometry (DEXA) scan to predict long-term force-transmission patterns in wrists. Material and Methods Both wrists of a man with morbid Kienböck stage IIIa disease of his left wrist (avascular necrosis of the lunate) were examined by a DEXA scan to determine the differences in bone density in the distal radius. Results In the distal radius of the injured wrist, a shift in bone density was seen toward the scaphoid fossa, which resembles the shift in force-transmission pattern described in force-transmission studies of the wrist. Conclusions These differences can be interpreted as a result of an altered force-transmission pattern in the injured wrist.
Acne successfully treated with acitretin in a patient with peanut allergy. Reply
Authors: S.A. Walsh, S.A. Holme
Journal: British Journal of Dermatology (2008)

Conflicts of interest: none declared. Sir, We read with interest the therapeutic experience of Laing and colleagues using acitretin to treat a patient with acne vulgaris and previous anaphylaxis to peanuts.1 Their rationale for this approach was that Roche Pharmaceutical’s isotretinoin (Roaccutane®; Roche, Welwyn Garden City, U.K.) contains arachis oil. The literature contains only a few reports of acitretin being a useful modality for acne vulgaris;2 other authors feel that isotretinoin is vastly superior in efficacy.3 We would like to draw attention to the availability of a generic formulation of isotretinoin that does not contain arachis oil and which may be suitable for use in patients when Roaccutane is contraindicated. We recently treated two patients with acne vulgaris and a history of anaphylaxis to peanuts using acitretin as an alternative to Roaccutane: a male patient aged 16 years (Leeds grade 11 face, 6 back) and a female patient aged 24 years (Leeds grade 7 face, 2 back). Both patients received a dose of 25 mg daily but neither had a detectable response to the treatment, and one experienced a considerable deterioration in severity of the acne. We became aware of a generic, arachis‐free formulation of isotretinoin (Beacon Pharmaceuticals Ltd, Tunbridge Wells, U.K.) and, having discussed the matter with our local pharmacist and the manufacturers, both patients were commenced on this treatment at a dose of 1 mg kg−1 daily for 4 months, with resolution of their eruptions.
Commentary: Nudging hospitals to better quality
Authors: A. Charlesworth, J. Dixon
Journal: BMJ (2013)

All developed countries are searching hard to eke more value out of the money spent on healthcare. First in line for analysis is hospital care—the most costly part of healthcare, accounting for 50% of costs in the NHS in England in 20011-12. One tool for controlling costs is the way that healthcare is paid for. Payments matter: they influence the services on offer, the viability of hospitals, the cost effectiveness of treatments, and how physicians practise medicine.

Western countries have been developing payments for hospital care over the past 20 years in similar ways. Busse and colleagues set out how and why payments for the care of homogeneous groups of patients (diagnosis related groups, DRGs) have evolved, their broad impact, and future likely direction.1

In the United States DRG payments curbed growth in Medicare hospital expenditures, partly through reduced inpatient stays.2 In Europe (including England) DRG payments have also been associated with reductions in the length of stay (and assumed …
Can Employers Exclude Women to Protect Children?
Authors: Mary E. Becker
Journal: JAMA (1990)

The U.S. Supreme Court has agreed to hear arguments in International Union, UAW v. Johnson Controls, Inc.. This case seeks to determine whether an employer may require a woman to be sterile to qualify for a production job involving exposure to lead, or whether such a policy violates Title VII of the 1964 Civil Rights Act. Six cases relating to this issue have reached state or federal appeals courts. Becker analyzes the social policy implications of attempts by employers to exclude fertile women from jobs when there is evidence of fetal risk from maternal exposure to harmful substances. She also discusses case law that has developed under Title VII litigation. Becker concludes that there are no strong policy reasons for allowing employers to exclude fertile women from some kinds of employment.
Regulation of Vascular Endothelial Growth Factor Receptor-1 Expression by Specificity Proteins 1, 3, and 4 in Pancreatic Cancer Cells
Authors: Maen Abdelrahim, Cheryl H. Baker, James L. Abbruzzese, David Sheikh-Hamad, Shengxi Liu, Sung Dae Cho, Kyungsil Yoon, Stephen Safe
Journal: Cancer Research (2007)

Abstract Vascular endothelial growth factor receptor-1 (VEGFR1) is expressed in cancer cell lines and tumors and, in pancreatic and colon cancer cells, activation of VEGFR1 is linked to increased tumor migration and invasiveness. Tolfenamic acid, a nonsteroidal anti-inflammatory drug, decreases Sp protein expression in Panc-1 and L3.6pl pancreatic cancer cells, and this was accompanied by decreased VEGFR1 protein and mRNA and decreased luciferase activity on cells transfected with constructs (pVEGFR1) containing VEGFR1 promoter inserts. Comparable results were obtained in pancreatic cancer cells transfected with small inhibitory RNAs for Sp1, Sp3, and Sp4 and all three proteins bound to GC-rich elements in the VEGFR1 promoter. These results show that VEGFR1 is regulated by Sp proteins and that treatment with tolfenamic acid decreases expression of this critical angiogenic factor. Moreover, in vitro studies in Panc-1 cells show that activation of VEGFR1 by VEGFB to increase mitogen-activated protein kinase 1/2 phosphorylation and cell migration on collagen-coated plates is also inhibited by tolfenamic acid. Thus, targeted degradation of Sp proteins is highly effective for inhibiting VEGFR1 and associated angiogenic responses in pancreatic cancer. [Cancer Res 2007;67(7):3286–94]
Multiple brushings with immediate Riu's stain via flexible fibreoptic bronchoscopy without fluoroscopic guidance in the diagnosis of peripheral pulmonary tumours.
Authors: C H Lee, C H Wang, M C Lin, T C Tsao, R S Lan, Y H Tsai, H P Kuo
Journal: Thorax (1995)

BACKGROUND--Accurate diagnosis of peripheral pulmonary lesions usually relies on fluoroscopic guided procedures. As fluoroscopy is not routinely available in many respiratory units, an approach not using fluoroscopy but with a high diagnostic yield is highly desirable. METHODS--Immediate cytological examination of multiple brushings using Riu9s stain, a modified Wright9s stain, was performed in 38 patients with peripheral pulmonary lesions not visible at bronchoscopy. The results were compared with the final diagnoses determined by histological examination or subsequent Papanicolaou staining of cytological specimens and clinical course. RESULTS--Of the 38 patients 29 were subsequently confirmed to have a malignant tumour. Our method provided a diagnosis of malignancy in 86% of these lesions. The accuracy (91%) and sensitivity (88%) were higher for lesions &gt; 3 cm in diameter than for those of diameter &lt; or = 3 cm (87% and 83%). There were no false positive results. The 29 lesions correctly diagnosed as malignant by Riu9s stain required significantly fewer brushings (mean (SD) 3 (2)) than the nine benign lesions (5 (4)). CONCLUSIONS--This technique provides a high diagnostic yield, avoids the need for fluoroscopy, and is probably safer than percutaneous biopsy.
A1.50 Extrathymic autoimmune regulator (AIRE) expression in rheumatoid arthritis synovial tissue
Authors: L F A Huitema, A R Noort, K P M van Zoest, M C Lebre, P P Tak, S W Tas
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Autoimmune Regulator (AIRE) is a transcription factor that is involved in the negative selection of self-reactive thymocytes in the thymus and therefore is pivotal in the establishment of central tolerance. Recently, AIRE has also been detected in secondary (or peripheral) lymphoid organs. In these secondary lymphoid organs, AIRE was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus, suggesting that extrathymic AIRE may play a complementary role in tolerance induction. It is currently unknown whether AIRE may also play a role in human chronically inflamed synovial tissue (ST) that sometimes contains ectopic lymphoid neogenesis (ELN). <h3>Objective</h3> To study whether extrathymic AIRE-expressing cells (eTACs) are present in ST of osteoarthritis (OA), psoriatic arthritis (PsA) or or rheumatoid arthritis (RA) patients with or without ELN. <h3>Methods</h3> ST was obtained via mini-arthroscopy from inflamed joints of OA, PsA or RA patients. Presence of AIRE protein was detected in ST cryosections by immunofluorescence staining and evaluated by confocal microscopy. <h3>Results</h3> ST from OA and PsA patients did not contain eTACs. Interestingly, eTACs were detected in some RA patients, but only in ST containing ELN. In these tissues eTACs were mainly found in large aggregates in the proximity of B-cells. The exact phenotype of eTACs in RA ST and their precise role in ELN are currently further investigated in our lab. <h3>Conclusion</h3> We demonstrate for the first time that eTACs can be found in chronic inflammation, more specifically in RA ST containing ELN. The presence of eTACs in RA ST may be an attempt to control inflammation through the induction of peripheral tolerance to antigens involved in the perpetuation of the inflammatory response. Eventually, advanced understanding of the function of eTACs in synovial inflammation may be exploited to develop new treatment modalities for RA patients.