tbuckley/cabot-search huggingface dataset:
Abstract 2489: Glycoproteomic analysis of breast cancer cell lines for biomarker discovery
Authors: Maria Arampatzidou, Majlinda Kullolli, Sharon J. Pitteri
Journal: Cancer Research (2014)

Abstract Glycosylation is one of the most ubiquitous protein post-translational modifications observed in eukaryotic organisms. In cancer, key cellular pathways and interactions, related to invasion and metastasis, are disrupted by altered protein glycosylation. Many current clinical cancer biomarkers are glycoproteins (i.e. CEA, CA15-5, CA125, and PSA). Glycosylation is known to be aberrant in breast cancer. However, systematic studies to identify glycoproteins in cancer have been limited, and typically focus on single proteins of interest or glycans released from proteins. We have developed a novel protein fractionation and enrichment strategy for glycoproteomic analysis of the secreted proteins, incorporating lectin affinity capture for glycoprotein enrichment, intact protein separation, and enzymatic digestion followed by LC-MS/MS analysis. Here, we apply this workflow to capture and analyze glycoproteins in the cancer secretome, which includes proteins secreted and/or shed from cancer cells into the extracellular space. Four breast cancer cell lines (HCC70, HCC1806, BT474, and ZR75-1) and one normal mammary epithelial cell line (MCF10A) were subjected to glycoproteomic analysis. Proteins corresponding to 3360 unique gene names were identified. Subsequent data analysis yielded a variety of types of information about glycoproteins in the cell line secretomes. 1) Fucosylated and branched-sugar containing glycoforms of proteins were identified by lectin binding properties. For example, PHA-P/PHA-L lectins showed high affinity for aldolase, immunoglobulins, and inter-alpha-trypsin inhibitor, suggesting these proteins contain branched sugar structures. 2) Enrichment of some proteins was observed in breast cancer cell lines compared to the normal mammary epithelial cell line and vice versa. For example, high expression of fucosylated vimentin was observed in MCF10A, but not breast cancer cell lines. 3) Differences in glycosylation patterns of proteins were observed between cell lines. For example, the protease legumain was observed to be highly fucosylated in MCF10A, but had a higher affinity for PHA-P/PHA-L in HCC70. Additional substrates and inhibitors of legumain were also identified. Proteins of interest were further studied in additional follow-up experiments including western blotting and glycostaining. Additional proteins of interest were measured in plasma samples from women with (benign or malignant) breast lesions. Citation Format: Maria Arampatzidou, Majlinda Kullolli, Sharon J. Pitteri. Glycoproteomic analysis of breast cancer cell lines for biomarker discovery. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2489. doi:10.1158/1538-7445.AM2014-2489
Simultaneous Endocardial Mapping in the Human Left Ventricle Using a Noncontact Catheter
Authors: Richard J. Schilling, Nicholas S. Peters, D. Wyn Davies
Journal: Circulation (1998)

Catheter ablation of ventricular tachycardia is limited in part by difficulty in identifying suitable sites for ablation. A noncontact multielectrode array (MEA) has been developed that allows reconstruction of 3360 electrograms, using inverse-solution mathematics, that are superimposed onto a computer-simulated model of the endocardium. This study assesses the accuracy of timing and morphology of reconstructed unipolar electrograms compared with contact unipolar electrograms from the same endocardial site.The MEA was deployed in the left ventricles of 13 patients (end-diastolic diameters, 61.7+/-8.4 mm [mean+/-SD]). We recorded contact electrograms at 76 points equatorial and 32 points nonequatorial to the MEA during sinus rhythm using a catheter-locator signal to record direction and distance from the MEA. Morphology (cross-correlation) and timing of maximum -dV/dt of contact and reconstructed electrograms were compared at different distances from the MEA center to endocardium (M-E) and from the MEA equatorial plane. For equatorial data, the M-E was 32.12+/-12.12 mm. The timing of reconstructed with respect to contact electrograms was -1.94+/-7.12 ms for M-E <34 mm and -14.16+/-19.29 ms at M-E >34 mm (P<0.001). Cross-correlation of electrograms was 0.87+/-0.12 (95% CI, 0.84 to 0.91) and 0.76+/-0.18 (95% CI, 0.69 to 0.83) for M-E <34 mm and >34 mm, respectively. Nonequatorial points were 32.33+/-10.81 mm (range, 16.9 to 55.6 mm) from the MEA equatorial plane; electrogram timing difference was -8.97+/-15.75 ms and was unrelated to this distance from the equator.This noncontact mapping system accurately reconstructs endocardial unipolar electrograms from the human left ventricle. At M-E distances >34 mm, timing accuracy of reconstruction decreases.
Serial Intravascular Ultrasound Analysis of the Main and Side Branches in Bifurcation Lesions Treated With the T-Stenting Technique
Authors: Joo-Yong Hahn, Young Bin Song, Sang-Yup Lee, Jin-Ho Choi, Seung-Hyuk Choi, Duk Kyung Kim, Sang Hoon Lee, Hyeon-Cheol Gwon
Journal: Journal of the American College of Cardiology (2009)
The 210-kD nuclear envelope polypeptide recognized by human autoantibodies in primary biliary cirrhosis is the major glycoprotein of the nuclear pore.
Authors: J C Courvalin, K Lassoued, E Bartnik, G Blobel, R W Wozniak
Journal: Journal of Clinical Investigation (1990)

We have recently reported a new family of nuclear autoantibodies in a subset of patients with primary biliary cirrhosis. These antibodies bind to a nuclear envelope polypeptide(s) of approximately 200 kD, the exact identity of which was not established. In this study, we show that all of these autoantibodies are directed against a 210-kD integral membrane glycoprotein of the nuclear pore.
Abstract 4673: Myopodin methylation is a prognostic marker in patients with T1G3 bladder cancer
Authors: Miguel Alvarez, Virginia Cebrian, Jesus Fernandez, Florentino Fresno, Safwan Escaf, Marta Sanchez-Carbayo
Journal: Cancer Research (2010)

Abstract BACKGROUND: Urothelial carcinomas presenting T1G3 non muscle-invasive lesions are high-risk tumors because of the high recurrence and progression to muscle invasive disease rates. The Bacillus of Calmette-Guérin (BCG) is a standard treatment to reduce tumor recurrence and delay progression of high-risk non-muscle invasive bladder tumors. However, it is not clear yet which T1G3 patients are more prone to display a more aggressive clinical behavior or be susceptible to respond to BCG. OBJECTIVE: The aim of this study was to evaluate the role of myopodin methylation as a clinical outcome prognosticator and predictive biomarker for BCG response in patients with T1G3 bladder tumors. DESIGN, SETTING, AND PARTICIPANTS: The methylation status of myopodin was analyzed on tumor specimens belonging to 170 patients with T1G3 non-muscle invasive bladder cancer, being a subset of them undergoing BCG treatment (n=108). MEASUREMENTS: Myopodin methylation was assessed by methylation-specific polymerase chain reactions. Recurrence, progression into muscle invasive tumors and disease-specific overall survival rates were analyzed using competing risks regression analysis. RESULTS: Among the 170 cases analyzed, 72 of them recurred (42.4%), 36 progressed (21.2%), and 24 died of the disease (14.1%). Univariate and multivariate survival analyses revealed that myopodin methylation was significantly associated with an increased recurrence rate (p=0.004), progression (p=0.002), and shorter disease-specific overall survival (p=0.020). Interestingly, in a subset of cases treated with BCG, myopodin methylation was also related to an increased recurrence rate (p=0.011), progression (p=0.030), and a shorter disease-specific overall survival (p=0.028). CONCLUSIONS: Epigenetic analyses revealed that myopodin methylation was associated with the clinical outcome of patients with T1G3 tumors. Myopodin methylation was related to tumor aggressiveness in patients with T1G3 disease undergoing BCG treatment. Myopodin methylation distinguished patients responding to BCG from those who may require a more aggressive therapeutic approach. 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 4673.
Cancer Rates Higher In Older People: But, Why?
Authors: J. Burklow
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Cancer Rates Higher In Older People: But, Why? Get access John Burklow John Burklow Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 17, 5 September 1990, Pages 1386–1387, https://doi.org/10.1093/jnci/82.17.1386 Published: 05 September 1990
<i>Int6</i> /eIF3e Silencing Promotes Functional Blood Vessel Outgrowth and Enhances Wound Healing by Upregulating Hypoxia-Induced Factor 2α Expression
Authors: Li Chen, Alexander Endler, Kazuyo Uchida, Shin-ichiro Horiguchi, Yoshihito Morizane, Osamu Iijima, Masakazu Toi, Futoshi Shibasaki
Journal: Circulation (2010)

We previously identified INT6/eIF3e as a novel regulator of hypoxia-inducible factor 2alpha (HIF2alpha) activity. Small interfering RNA (siRNA)-Int6 adequately stabilized HIF2alpha, even under normoxic conditions, and thereby enhanced the expression of several angiogenic factors in vitro, suggesting that siRNA-Int6 may induce angiogenesis in vivo.We demonstrated a 6- to 8-fold enhanced formation of normal arteries and veins in the subcutaneous regions of adult mice 5 days after a single siRNA-Int6 application. Subcutaneous fibroblasts were identified as the major source of secreted angiogenic factors that led to the formation of functional vessels during Int6 silencing. Fibroblasts transfected ex vivo with siRNA-Int6 induced potent neoangiogenesis when transplanted into a subcutaneous region of nude mice. Application of siRNA-Int6 promoted neoangiogenesis in the area surrounding the injury in wound healing models, including genetically diabetic mice, thereby accelerating the closure of the injury. HIF2alpha accumulation caused by siRNA-Int6 was confirmed as the unequivocal cause of the angiogenesis by an in vivo angiogenesis assay. Further analysis of the Int6 silencing-induced neoangiogenesis revealed that a negative feedback regulation of HIF2alpha stability was caused by HIF2alpha-induced transcription of Int6 via hypoxia-response elements in its promoter. Thus, siRNA-Int6 temporarily facilitates an accumulation of HIF2alpha protein, leading to hypoxia-independent transcription of angiogenic factors and concomitant neoangiogenesis.We suggest that the pathway involving INT6/HIF2alpha acts as a hypoxia-independent master switch of functional angiogenesis; therefore, siRNA-Int6 application might be of clinical value in treating ischemic diseases such as heart and brain ischemia, skin injury, and diseases involving obstructed vessels.
Alterations in ventricular contraction pattern in the Wolff-Parkinson-White syndrome. Detection by echocardiography.
Authors: A N DeMaria, Z Vera, A Neumann, D T Mason
Journal: Circulation (1976)

The effects of abnormal ventricular activation upon the contractile pattern of the ventricles in patients with the Wolff-Parkinson-White syndrome (WPW) remain uncertain. Therefore we compared the motion of the anterior right ventricular wall (RV), the interventricular septum (IVS), and left ventricular posterior wall (LVPW) on echogram in nine patients with WPW and one patient with a coronary sinus pacemaker (CSP) to 20 normal subjects. Normal subjects manifested posterior RV motion which began and reached maximal excursion at 175 and 366 msec (group mean), respectively, after the onset of the QRS complex; posterior movement of the IVS which started and peaked at 90 and 30 msec, respectively; and anterior contraction of the LVPW which began and peaked at 159 and 406 msec, respectively. Five of seven patients with Type A WPW demonstrated a localized area of premature contraction of the LVPW occuring during the initial 100 msec interval following the onset of the QRS complex which was accompanied by paradoxic anterior motion of the IVS. Thereby in Type A patients initial and maximal posterior motion of the IVS occurred later, 230 (P less than 0.001) and 400 (P less than 0.05) msec, and anterior motion of the LVPW occurred earlier, 75 (P less than 0.001) and 367 (P less than 0.05) msec as compared to normal. The amplitude and duration of early contraction could be related to the prominence of the delta wave during atrial pacing. Similar premature contraction was also observed in the patient with CSP during paced beats. One Type B WPW patient exhibited abnormal IVS motion while the additional patient manifested premature LVPW contraction similat to that seen in Type A patients. The contractile pattern of the right ventricular anterior wall was recorded in five of seven Type A Wolff-Parkinson-White patients and manifested prolongation of the interval from the onset of the QRS complex to the initial posterior movement (group mean 234 msec, P less than 0.05) as compared to normal. Thus echocardiography can be used to confirm the diagnosis and to improve understanding of the pathophysiology of the Wolff-Parkinson-White syndrome.
Perioperative Comparison of Robotic Assisted Laparoendoscopic Single-Site (LESS) Pyeloplasty Versus Conventional LESS Pyeloplasty
Authors: Ephrem O. Olweny, Samuel K. Park, Yung K. Tan, Cenk Gurbuz, Jeffrey A. Cadeddu, Sara L. Best
Journal: European Urology (2011)
Dominant-Negative Suppression of HCN Channels Markedly Reduces the Native Pacemaker Current <i>I</i> <sub>f</sub> and Undermines Spontaneous Beating of Neonatal Cardiomyocytes
Authors: Fikret Er, Robert Larbig, Andreas Ludwig, Martin Biel, Franz Hofmann, Dirk J. Beuckelmann, Uta C. Hoppe
Journal: Circulation (2003)

Background— The pacemaker current I f contributes to spontaneous diastolic depolarization of cardiac autonomic cells. In heterologous expression, HCN channels exhibit a hyperpolarization-activated inward current similar to I f . However, the links between HCN genes and native I f are largely inferential, and it remains unknown whether I f is essential for cardiac pacing. Methods and Results— To clarify this situation, we generated a GYG 402–404 AYA pore mutation of HCN2, which rendered the channel nonfunctional and suppressed wild-type HCN2 in a dominant-negative manner in Chinese hamster ovary cells. In addition, HCN2-AYA suppressed I HCN4 in a dominant-negative manner when coexpressed with wild-type HCN4, indicating that the 2 isoforms HCN2 and HCN4 are able to coassemble to form heteromultimeric complexes. Given that HCN2 and HCN4 are the dominant HCN mRNA transcripts in neonatal rat ventricle, we expressed HCN2-AYA in neonatal cardiocytes using adenoviral gene transfer to test the effect of HCN suppression on native I f . I f density was indeed reduced markedly, from 7.8±1.6 pA/pF (n=13) in control cells to 0.3±0.2 pA/pF (n=11) in HCN2-AYA–infected cells when measured at −130 mV ( P &lt;0.001). To probe the effect of HCN on cardiac pacing, we infected spontaneously beating neonatal monolayers with adenoviral vectors expressing wild-type and mutant HCN channels. Infection with HCN2 and HCN4 accelerated the beating rate significantly, to 230.5±8.6 bpm (n=12) and 223.5±12.3 bpm (n=10), respectively, compared with control cultures (83.4±4.5 bpm, n=13, P &lt;0.001). Conversely, HCN2-AYA completely undermined spontaneous pacing of neonatal cardiocytes. Conclusions— HCN channels are the major molecular component of native I f and are critical for spontaneous beating of neonatal cardiomyocytes.
Low dose blockade in acute stroke ("BEST" trial): an evaluation
Authors: D H Barer, J M Cruickshank, S B Ebrahim, J R A Mitchell
Journal: BMJ (1988)

The β blocker stroke (“BEST”) trial was designed to see if the apparent protective effect of propranolol on cerebral function in patients with subarachnoid haemorrhage applied also to patients suffering from acute stroke. Three hundred and two conscious patients with clinically diagnosed hemispheric strokes sustained within the past 48 hours were randomly assigned to receive atenolol, propranolol, or matching placebo capsules for three weeks. More early deaths occurred among the patients allocated to receive β blockers, but this was largely explained by differences in the initial characteristics of the patients among the different treatment groups. By contrast, the outcome in a further 60 patients, who had been taking β blockers at the time of their stroke but were otherwise similar to the patients in the trial, was considerably better, suggesting that prior treatment with β blockers might be protective. The search for an effective medical treatment for acute stroke must continue. The approach used here, in which neurological outcome was assessed in a modest number of patients with a view to proceeding subsequently to a full scale trial of functional outcome, allows practical benefits of a treatment to be evaluated under realistic conditions and an ineffective treatment to be eliminated without undue cost.
Domiciliary nebulisers in asthma: a district survey.
Authors: C M Laroche, A V Harries, R C Newton, M G Britton
Journal: BMJ (1985)

Fifty three patients who were found to be using a home nebuliser for asthma completed a questionnaire. The results showed some confusion about the criteria for recommending whether a patient should buy a nebuliser and for its correct use. Twelve patients had not received any instruction on the use of their nebuliser, and only 11 of those old enough used a peak flow meter in conjunction with it. Eight patients aged 7-15 were using inhaled sympathomimetic aerosols only at the time of buying a nebuliser as compared with most of the older patients, who were using regular oral steroids. Forty nine patients assessed their asthma as moderate to severe, but eight of these were not attending a hospital clinic. Several patients were using 20 mg salbutamol or more every day, and on occasion doses of up to 50 mg a day were reported. It is recommended that patients should be assessed before they buy a nebuliser and advice given on correct use by a district nebuliser service, organised either by respiratory function technicians or in physiotherapy departments for adults together with a paediatric health visitor for children.
Patient care drives mandatory vaccination
Authors: S. B Lambert
Journal: BMJ (2008)

Both sides debating mandatory flu vaccination for healthcare workers canvass central arguments,1 2 but key issues require further exploration.

Neither side acknowledged that health care differs fundamentally from other work. Its primary aim is not individual protection but protection of patients by reducing nosocomial flu. John Stuart Mills would support, not oppose, a mandatory programme.2

The autonomy argument focuses …
Acute hyperglycaemia affects anorectal motor and sensory function in normal subjects
Authors: A Russo, W M Sun, Y Sattawatthamrong, R Fraser, M Horowitz, J M Andrews, N W Read
Journal: Gut (1997)

Background —The pathogenesis of anorectal dysfunction, which occurs frequently in patients with diabetes mellitus, is poorly defined. Recent studies indicate that changes in the blood glucose concentration have a major reversible effect on gastrointestinal motor function. Aims —To determine the effects of physiological changes in blood glucose and hyperglycaemia on anorectal motor and sensory function in normal subjects. Subjects —In eight normal subjects measurements of anorectal motility and sensation were performed on separate days while blood glucose concentrations were stabilised at 4, 8, and 12 mmol/l. Methods —Anorectal motor and sensory function was measured using a sleeve/sidehole catheter incorporating a balloon, and electromyography. Results —The number of spontaneous anal relaxations was greater at 12 mmol/l than at 8 and 4 mmol/l glucose (p&lt;0.05 for both). Anal squeeze pressures were less at a blood glucose of 12 mmol/l when compared with 8 and 4 mmol/l (p&lt;0.05 for both). During rectal distension, residual anal pressures were not significantly different between the three blood glucose concentrations. Rectal compliance was greater (p&lt;0.05) at a blood glucose of 12 mmol/l when compared with 4 mmol/l. The threshold volume for initial perception of rectal distension was less at 12 mmol/l when compared with 4 mmol/l (40 (20–100) ml versus 10 (10–150) ml, p&lt;0.05). Conclusions —An acute elevation of blood glucose to 12 mmol/l inhibits internal and external anal sphincter function and increases rectal sensitivity in normal subjects. In contrast, physiological changes in blood glucose do not have a significant effect on anorectal motor and sensory function.
The truth is out there
Authors: A. Forrest
Journal: BMJ (1997)

I discovered the potential of cognitive behaviour therapy (CBT) while suffering from a depressive illness that proved to be resistant to a wide range of physical treatments. My illness was regarded as largely biological in origin but after 18 months of treatment, including 12 weeks as an inpatient and several combinations of medication, it was suggested that I might find CBT beneficial.

I had little idea of what cognitive therapy involved, but I understood it to be a pragmatic problem solving treatment rather than one which involved delving into the dark recesses of my past. I had already had a single session of the dark recesses variety and neither I nor the therapist felt that this type of therapy was likely to be of any benefit to me. Unlike many forms of psychotherapy CBT is collaborative. The patient and therapist work together to clarify problems and suggest possible solutions. It is then left largely to the patient to try out these solutions as homework and discuss the outcome at the next therapy session.

The behavioural element of CBT aims to modify dysfunctional behaviour …
Lung Disease: State of the Art, 1978-1979
Authors: Paul T. Davidson
Journal: JAMA (1981)

This monograph contains 13 state of the art articles originally published in the American Review of Respiratory Disease and is the fifth of a series that started in 1974. Each chapter was selected because of its importance and for its treatment of new advances in lung disease knowledge. Complete reviews of all the topics are provided by expert authors. Each contains an extensive bibliography, an invaluable resource to the reader. All of the material should be of great interest to the practicing clinician and to the investigator and teacher.  The chapters Non-tuberculous Mycobacteria and Associated Diseases and Blastomycosis are the best and most complete reviews of these uncommon but important chronic infections available in the current literature. The complex subjects of growth and development, genetics, and malformations of the respiratory system are expertly elucidated in two chapters that should prove to be classics. The nerve supply to the lungs is
PROGNOSTIC SIGNIFICANCE OF RIGHT VENTRICULAR STRUCTURE AND FUNCTION IN SLEEP DISORDERED BREATHING AND NORMAL EJECTION FRACTION
Authors: Dermot Phelan, Sinziana Seicean, Kenya Kusunose, Andreea Seicean, Patrick Collier, Kaeleen Boden, Nima Alan, Brian Griffin
Journal: Journal of the American College of Cardiology (2014)