tbuckley/cabot-search huggingface dataset:
Abstract 5168: Gastric adenocarcinomas show pervasive loss of heterozygosity and enrichment for “STOP” genes in regions of hemizygous deletion
Authors: Ioana Cutcutache, Alice Yingting Wu, John R. McPherson, Zhengdeng Lei, Niantao Deng, Wai Keong Wong, Khee Chee Soo, Weng Hoong Chan, London Lucien Ooi, Roy E. Welsch, Patrick Tan, Steven G. Rozen
Journal: Cancer Research (2014)

Abstract Purpose: Gastric cancer, the second leading cause of cancer death worldwide, has been little studied compared with other cancers that impose similar burdens on public health. Our goal is to assess loss of heterozygosity (LOH) and hemizygous deletion across a large series of gastric adenocarcinomas using the most sensitive and comprehensive method currently available. Experimental design: We used high-density single-nucleotide-polymorphism microarrays that assay genotype and copy number at 906,600 sites and analyzed the results to determine patterns of LOH and hemizygous deletion in 77 gastric adenocarcinomas. We investigated whether “STOP” genes - genes that tend to impede proliferation - are associated with hemizygous deletion. We also analyzed the extent to which hemizygous deletion affected CYCLOPS (Copy number alterations Yielding Cancer Liabilities Owing to Partial losS) genes - genes that may be attractive targets for therapeutic inhibition when hemizygously deleted. Results: We found that LOH is pervasive: on average 27% of each tumor genome is subject to LOH, and &amp;gt; 98% of single nucleotide polymorphisms assayed were subject to LOH in at least 10% of tumors. Furthermore, 26% of LOH was due to hemizygous deletion, and STOP genes were significantly associated with regions of frequent hemizygous deletion; on average, 61 STOP genes were hemizygously deleted per tumor. Furthermore, on average, 4.65 CYCLOPS genes were hemizygously deleted per tumor, and 54.5% of the tumors had at least one CYCLOPS gene deleted. Conclusions: These findings suggest that hemizygous deletion of anti-proliferative STOP genes contributes substantially to gastric carcinogenesis. Furthermore, the presence of several hemizygously deleted CYLOPS genes in some tumors suggests potential therapeutic targets in these tumors. Citation Format: Ioana Cutcutache, Alice Yingting Wu, John R. McPherson, Zhengdeng Lei, Niantao Deng, Wai Keong Wong, Khee Chee Soo, Weng Hoong Chan, London Lucien Ooi, Roy E. Welsch, Patrick Tan, Steven G. Rozen. Gastric adenocarcinomas show pervasive loss of heterozygosity and enrichment for “STOP” genes in regions of hemizygous deletion. [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 5168. doi:10.1158/1538-7445.AM2014-5168
Pharmacological studies of the involvement of hypothalamic prostaglandins in the regulation of thyrotropin secretion.
Authors: K C Wright, G A Hedge
Journal: Environmental Health Perspectives (1981)

A case is made for the involvement of pituitary prostaglandins (PGs) in the regulation of thyrotropin (TSH) secretion by citing recent evidence that TSH release in vivo and in vitro is enhanced by treatment with exogenous PGs and is inhibited by drugs (e.g., indomethacin) that block PG synthesis. Pharmacological studies were then performed to test the hypothesis that hypothalamic PGs also affect TSH secretion indirectly via the appropriate hypothalamic hormones that regulate pituitary secretion. The inhibition of thyroidectomy-induced TSH secretion was used as an endpoint in choosing the best of several drugs purported to inhibit PG synthesis. The established effectiveness of indomethacin and aspirin were used for reference in testing the following drugs: naproxen, mefenamic acid, tranylcypromine, and phenelzine. Only naproxen was found to be effective, but since it was no more potent than indomethacin, the latter drug was used for subsequent work. Indomethacin was stereotaxically implanted into several hypothalamic regions known to regulate TSH secretion, and sequential plasma samples were analyzed for TSH by radioimmunoassay. Bilateral implants of indomethacin in the anterior hypothalamic area increased TSH secretion throughout the 72 hr period of study. Sham inplants at this site and indomethacin implants in other nearby sites were ineffective. These findings suggest that endogenous PGs play an inhibitory role in the hypothalamic regulation of pituitary secretion.
Cardiac Pacing in the Elderly
Authors: Robert M. Jeresaty
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The brief communication by Colokathis et al (<b>217</b>:80, 1971) and the four cases of pacemaker implantation in the elderly reported inThe Journal(<b>218</b>:95-96, 1971) prompt us to report our favorable experience with pacing for complete heart block in four elderly patients aged 96, 96, 91, and 88 years, respectively. <h3>Report of Cases.—Case 1.—</h3> An endocardial pacemaker was implanted in April 1970 in a 96-year-old woman. She is still alive, ambulatory, and mentally competent. Case2.—An endocardial pacemaker was implanted in May 1970 in a 96-year-old woman after an Adams-Stokes episode. She is alive and well a year and a half after implantation. Case3.—An endocardial pacemaker was implanted in June 1968 in this 91-year-old patient with trifascicular block and syncopal episodes. He is asymptomatic, mentally alert, and active 3 1/2 years after implantation. Case4.—An endocardial pacemaker was implanted in October 1966 in
Long-term stability of cell micropatterns on poly((3-(methacryloylamino)propyl)-dimethyl(3-sulfopropyl)ammonium hydroxide)-patterned silicon oxide surfaces
Authors: Woo Kyung Cho, Bokyung Kong, Hyung Ju Park, Jinkyu Kim, Won Chegal, Joon Sig Choi, Insung S. Choi
Journal: Biomaterials (2010)
Switching off Embolization From Symptomatic Carotid Plaque Using <i>S</i> -Nitrosoglutathione
Authors: Zoltan Kaposzta, John F. Martin, Hugh S. Markus
Journal: Circulation (2002)

Background — Current antiplatelet regimens fail to prevent the majority of recurrent strokes. Asymptomatic circulating emboli can be detected by transcranial Doppler ultrasound, are frequent in patients with symptomatic carotid stenosis, and predict recurrent stroke risk. S -Nitrosoglutathione (GSNO) is a nitric oxide donor that appears to have relative platelet specificity. We evaluated its effectiveness in reducing embolization in patients with symptomatic carotid stenosis who already were taking aspirin. Methods and Results — Twenty patients with ≥50% internal carotid artery stenosis and with ≥3 embolic signals detected during a half-hour screening recording were recruited. All had taken aspirin for at least 7 days. They were randomly assigned in a double-blind fashion to either GSNO (4.4 mmol/kg per minute) or saline placebo for 90 minutes. Transcranial Doppler recordings were made from the ipsilateral middle cerebral artery for 1 hour before treatment and at 0 to 3, 6, and 24 hours after treatment. Before treatment, the mean (range) of embolic signals per hour was 6.9 (3 to 13) in the GSNO group and 7.3 (4 to 12) in the placebo group ( P =0.68). GSNO resulted in a rapid reduction in the frequency of embolic signals of 84% at 0 to 3 hours, 95% at 6 hours, and 100% at 24 hours ( P &lt;0.0001, P =0.003, and P &lt;0.0001 versus placebo, respectively). Conclusions — Continued embolization is common in patients with carotid stenosis despite aspirin therapy. GSNO was highly effective in rapidly reducing the frequency of embolic signals in this patient group. Despite its short administration time and its short half-life, it resulted in therapeutic effects lasting 24 hours.
Estimation of Respiratory Drive with Carbon Dioxide and Helium
Authors: JOSEPH L. GRANT
Journal: Annals of Internal Medicine (1971)

Fourteen patients with obstructive emphysema showed less rise in ventilation while breathing 3, 5, and 7% carbon dioxide than did 19 normal subjects. This may have been caused either by airway obstruction or by respiratory center depression. When helium replaced nitrogen as the balance gas, oxygen remaining at 21%, the patients increased their ventilation as much as the normal subjects. Helium has been shown to reduce airway resistance, and these results suggest that in this group of patients airway obstruction was the important cause of decreased ventilation. Measurement of the ventilatory response to carbon dioxide and helium offers a promising means of differentiating between respiratory-center depression and airway obstruction.
Autoimmunity and Inflammation Due to a Gain-of-Function Mutation in Phospholipase Cγ2 that Specifically Increases External Ca2+ Entry
Authors: Philipp Yu, Rainer Constien, Neil Dear, Matilda Katan, Petra Hanke, Tom D. Bunney, Sandra Kunder, Leticia Quintanilla-Martinez, Ulrike Huffstadt, Andreas Schröder, Neil P. Jones, Thomas Peters, Helmut Fuchs, Martin Hrabe de Angelis, Michael Nehls, Johannes Grosse, Philipp Wabnitz, Thomas P.H. Meyer, Kei Yasuda, Matthias Schiemann, Christian Schneider-Fresenius, Wolfgang Jagla, Andreas Russ, Andreas Popp, Michelle Josephs, Andreas Marquardt, Jürgen Laufs, Carolin Schmittwolf, Hermann Wagner, Klaus Pfeffer, Geert C. Mudde
Journal: Immunity (2005)
Utility of the ratio of food‐specific IgE/total IgE in predicting symptomatic food allergy in children
Authors: A. Mehl, A. Verstege, U. Staden, M. Kulig, M. Nocon, K. Beyer, B. Niggemann
Journal: Allergy (2005)

Background: Double‐blind, placebo‐controlled food challenges are time‐consuming, expensive and not without risk to patients. Therefore, an in vitro test that could accurately diagnose food allergy would be of great value. Objective: To evaluate the utility of the ratio of specific immunoglobulin E (IgE)/total IgE compared with specific IgE (sIgE) alone in predicting symptomatic food allergy. Methods: We retrospectively analysed 992 controlled oral food challenges performed in 501 children (median age 13 months). The ratio of sIgE/total IgE was calculated and tested for correlation with the outcome of food challenges. Receiver operator characteristics (ROC)‐curves were performed; predicted probabilities and predictive decision points were calculated. Results: A significant correlation was found between the ratio and the outcome of food challenges for cow's milk (CM), hen's egg (HE), and wheat, but not for soy. The ROC and predicted probability curves as well as sensitivity and specificity of the decision points of the ratio were similar to those of sIgE levels for CM, HE and wheat. Conclusion: In view of the greater effort needed to determine the ratio, without benefit compared with the sIgE alone, the calculation of the ratio of sIgE/total IgE for diagnosing symptomatic food allergy offers no advantage for CM, HE, wheat or soy. For the majority of cases controlled oral food challenges still remain the method of choice.
Paclitaxel-Induced Nuclear Translocation of FOXO3a in Breast Cancer Cells Is Mediated by c-Jun NH2-Terminal Kinase and Akt
Authors: Andrew Sunters, Patricia A. Madureira, Karen M. Pomeranz, Muriel Aubert, Jan J. Brosens, Simon J. Cook, Boudewijn M.T. Burgering, R. Charles Coombes, Eric W.-F. Lam
Journal: Cancer Research (2006)

Abstract The microtubule-targeting compound paclitaxel is often used in the treatment of endocrine-resistant or metastatic breast cancer. We have previously shown that apoptosis of breast cancer cells in response to paclitaxel is mediated by induction of FOXO3a expression, a transcription factor downstream of the phosphatidylinositol-3-kinase/Akt signaling pathway. To further investigate its mechanism of action, we treated MCF-7 cells with paclitaxel and showed a dose-dependent increase in nuclear localization of FOXO3a, which coincided with decreased Akt signaling but increased c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) activity. Flow cytometry revealed that paclitaxel-induced apoptosis of MCF-7 cells and of other paclitaxel-sensitive breast cancer cell lines was maintained in the presence of inhibitors of p38 (SB203580) or mitogen-activated protein/ERK kinase 1 signaling (PD98059) but abrogated when cells were treated with the JNK1/2 inhibitor SP600125. SP600125 reversed Akt inhibition and abolished FOXO3a nuclear accumulation in response to paclitaxel. Moreover, conditional activation of JNK mimicked paclitaxel activity and led to dephosphorylation of Akt and FOXO3a. Furthermore, mouse embryonic fibroblasts (MEF) derived from JNK1/2 knockout mice displayed very high levels of active Akt, and in contrast to wild-type MEFs, paclitaxel treatment did not alter Akt activity or elicit FOXO3a nuclear translocation. Taken together, the data show that cell death of breast cancer cells in response to paclitaxel is dependent upon JNK activation, resulting in Akt inhibition and increased FOXO3a activity. (Cancer Res 2006; 66(1): 212-20)
Abstract 1412: Capturing c-Myb target genes in adenoid cystic carcinoma
Authors: KATHRYN BRAYER, Scott Ness
Journal: Cancer Research (2014)

Abstract Mutated versions of c-Myb are potent oncoproteins, and Myb proteins are over- or highly-expressed in a wide variety of human tumors. Adenoid Cystic Carcinoma (ACC), the second most frequent malignancy of minor and major salivary glands, frequently contains a recurrent t(6;9) translocation which fuses the c-Myb proto-oncogene on chromosome 6q to the NFIB gene on chromosome 9p resulting in the expression of novel Myb-NFIB fusion oncoproteins. These variants of c-Myb play a definitive role in development of ACC tumors, and are the first evidence that Myb proteins function as “driver” mutations in human cancer. Identifying target genes directly regulated by Myb-NFIB oncoproteins in ACC tumors can help determine how Myb proteins transform cells and contribute to tumor development in ACC. Genomics analyses of solid tumors is challenging because tumors are often heterogeneous tissue types and are often not stored in a manner that preserves labile nucleic acids. FFPE samples offer the most promise since formaldehyde fixation effectively “locks” the Myb-NFIB fusion proteins and epigenetic marks, such as modified histones, to the genes of interest. We have developed improved methods were for extracting chromatin from FFPE samples for use in chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq) and are applying these technical innovations to ACC tumors preserved in FFPE. When combined with gene expression information provided by RNA-seq analysis, ChIP-seq analysis of c-Myb gene targets will identify regulators that can be targets in novel therapeutic strategies in the future, as well as provide a greater understand of c-Myb functions in ACC and other epithelial tumors in which Myb plays a role. Citation Format: KATHRYN BRAYER, Scott Ness. Capturing c-Myb target genes in adenoid cystic carcinoma. [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 1412. doi:10.1158/1538-7445.AM2014-1412
An Unusual Presentation of Non-Hodgkin’s Lymphoma
Authors: SUDHA CHALLA, ELIAS H. BOTVINICK, EDWARD NEYMARK, DAVID PRICE, RANDALL A HAWKINS
Journal: Clinical Nuclear Medicine (2000)

A 40-year-old woman was examined for a sudden onset of malignant hypertension. When she was normotensive after symptomatic treatment, a captopril renogram was performed and showed decreased left renal perfusion. Although a conventional angiogram did not reveal significant renal artery stenosis, a subsequent contrast-enhanced abdominal CT scan showed a large soft-tissue mass encasing the left renal artery. Biopsy showed this to be a non-Hodgkin’s lymphoma. A whole-body Ga-67 scan revealed tracer uptake in the left perirenal area with no evidence of other sites of lymphoma. A postchemotherapy CT scan of the abdomen at 6 months showed nearly complete resolution of the perirenal mass. FIGURE 1Fig. 1: (A) Perfusion phase (posterior projection; the left is to the reader’s left) of the captopril renogram shows decreased and delayed flow to the left kidney. (B) The delayed phase of the captopril renogram shows slow uptake and washout of the tracer.FIGURE 2Fig. 2: A selected left renal angiogram shows no evidence of renal artery stenosis.FIGURE 3Fig. 3: (A) A contrast-enhanced CT scan of the abdomen at the level of both kidneys shows the large left perirenal mass encasing the left renal artery. (B) An abdominal CT scan was repeated 6 months after chemotherapy was begun. This follow-up scan shows nearly complete regression of the perirenal lymphoma.FIGURE 4Fig. 4: A pretherapy Ga-67 scan shows intense uptake of Ga-67 within the left perirenal lymphoma.
The gastrointestinal tract, an infrequent target for Waldenström's macroglobulinemia
Authors: P. Rodríguez, C. Sánchez, M. Bolino, L. Caro, C. Cerisoli, D. Miserendino, B. Elsner, H. Ferro, A. Vijnovich
Journal: Endoscopy (2010)

Waldenström's macroglobulinemia is a rare hematological neoplasm that infrequently involves the gastrointestinal tract.
Risky Delay of Hypoglycemia Detection by Glucose Monitoring at the Arm
Authors: Karsten Jungheim, Theodor Koschinsky
Journal: Diabetes Care (2001)

Several devices for self-monitoring of blood glucose (SMBG) (e.g., AtLast, Amira; OneTouch Ultra, LifeScan; FreeStyle, TheraSense, Alameda, CA; Glucometer-Elite XL+Microlet-Vaculance, Bayer; and Sof-Tact, Abbott) recently received Food and Drug Administration approval for alternative site monitoring of capillary blood glucose. These alternatives are marketed with considerable efforts under the assumption that capillary blood glucose measurements, e.g., those taken at the forearm, do not differ from the results obtained by classic finger pricking. Diabetic patients using different devices for SMBG reported discrepancies between clinical symptoms of hypoglycemia and normoglycemic SMBG values at the forearm. Neither standardized quality control assessments of technical performance of such SMBG devices (1,2) nor patient device handling resulted in any obvious explanation of the reported discrepancies. Because of this, we examined …
Drugs used in US executions are supplied by a UK company, investigation shows
Authors: S. Mayor
Journal: BMJ (2011)

A UK company owned by a businessman who also runs a small driving school in west London has supplied drugs to the United States to be used in some forms of execution by lethal injection, found an investigation carried out by Reprieve UK, a charity that uses the law to enforce prisoners’ rights, and the BBC. 

The investigation, reported by the BBC on 6 January, found an invoice from the company, Dream Pharma, for three drugs used in some forms of lethal injection for execution in the US, with the same date as an email between US prison officials confirming that they had obtained the three drugs from a company in London.

Clive Stafford Smith, director of Reprieve UK, has called on the UK government to impose an immediate export ban on two of the drugs (pancuronium bromide and potassium chloride), after the government’s recent introduction of a scheme requiring a licence for the export of the …
Beyond Atopy
Authors: Angela Simpson, Vincent Y. F. Tan, John Winn, Markus Svensén, Christopher M. Bishop, David E. Heckerman, Iain Buchan, Adnan Custovic
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

The pattern of IgE response (over time or to specific allergens) may reflect different atopic vulnerabilities which are related to the presence of asthma in a fundamentally different way from current definition of atopy.To redefine the atopic phenotype by identifying latent structure within a complex dataset, taking into account the timing and type of sensitization to specific allergens, and relating these novel phenotypes to asthma.In a population-based birth cohort in which multiple skin and IgE tests have been taken throughout childhood, we used a machine learning approach to cluster children into multiple atopic classes in an unsupervised way. We then investigated the relation between these classes and asthma (symptoms, hospitalizations, lung function and airway reactivity).A five-class model indicated a complex latent structure, in which children with atopic vulnerability were clustered into four distinct classes (Multiple Early [112/1053, 10.6%]; Multiple Late [171/1053, 16.2%]; Dust Mite [47/1053, 4.5%]; and Non-dust Mite [100/1053, 9.5%]), with a fifth class describing children with No Latent Vulnerability (623/1053, 59.2%). The association with asthma was considerably stronger for Multiple Early compared with other classes and conventionally defined atopy (odds ratio [95% CI]: 29.3 [11.1-77.2] versus 12.4 [4.8-32.2] versus 11.6 [4.8-27.9] for Multiple Early class versus Ever Atopic versus Atopic age 8). Lung function and airway reactivity were significantly poorer among children in Multiple Early class. Cox regression demonstrated a highly significant increase in risk of hospital admissions for wheeze/asthma after age 3 yr only among children in the Multiple Early class (HR 9.2 [3.5-24.0], P < 0.001).IgE antibody responses do not reflect a single phenotype of atopy, but several different atopic vulnerabilities which differ in their relation with asthma presence and severity.
The Immunology of Exercise
Authors: Harvey B. Simon
Journal: JAMA (1984)

Many athletes believe that habitual exercise protects them against infection. This article reviews ten studies of the effects of exercise on various host-defense factors. Exercise produced a transient granulocytosis and lymphocytosis, and in some studies, lymphocyte function was reported to have been enhanced. Serum immunoglobulin and complement levels were not significantly altered in the small number of subjects studied. Two recent studies showed that exercise produced an increase in circulating endogenous pyrogen in man. Since it now appears that endogenous pyrogen is identical to interleukin-1, a product of mononuclear cells that enhances lymphocyte function, it may play a role in host defense. Further studies will be needed before it can be concluded that exercise effects the host response to infection in any clinically meaningful way.