tbuckley/cabot-search huggingface dataset:
Abstract P6-04-17: The androgen metabolite-dependent growth in hormone receptor positive breast cancer as a novel aromatase inhibitor-resistance mechanism
Authors: T Hanamura, T Niwa, S Nishikawa, H Konno, T Ghono, Y Kobayashi, M Kurosumi, H Takei, Y Yamaguchi, K-I Ito, S-I Hayashi
Journal: Cancer Research (2012)

Abstract Introduction: Aromatase inhibitors (AIs) have been reported to exert their anti-proliferative effects not only by reducing the production of estrogens but also by unmasking the inhibitory effect of androgens such as testosterone (TS) or dihydrotestosterone (DHT) in postmenopausal women with hormone receptor-positive breast cancer. The behavior of androgens in AI-resistance mechanisms is not sufficiently understood. 5α-androstane-3β,17β-diol (3β-diol) generated from DHT by 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD type 1: HSD3B1) has androgenic activity and substantial estrogenic activity, representing a potential mechanism of AI resistance. Methods: To investigate these issues, ERE-GFP-transfected MCF-7-E10 cells were cultured for 3 months under steroid-depleted, TS-supplemented conditions which is the similar as the AI treatment. Among the surviving cells, two stable variants that show ER activity depending on androgen metabolites were selected as AD-EDR (androgen metabolite-dependent and estrogen depletion-resistant) by monitoring GFP expression. Using these cell lines, we investigated the process of adaptation to androgen-abundant conditions and the role of androgens in AI-resistance mechanisms. Results: AD-EDR cell lines showed increased growth and induction of estrogen-responsive genes rather than androgen-responsive genes by androgens or 3β-diol. Further analysis revealed increased expressions of HSD3B1 and reduced expression of androgen receptor (AR) in these cell lines. In parental MCF-7-E10 cells, ectopic expression of HSD3B1 or inhibition of AR resulted in adaptation to estrogen-deprived and androgen-abundant conditions. In coculture with stromal cells replicating the local estrogen production from androgen, AD-EDR cell lines showed AI resistance compared with parental MCF-7-E10 cells. Immunohistochemistry and real-time PCR analyses on 9 pairs of primary and recurrent tissue samples from AI-resistant breast cancer revealed the decrease of AR protein expression in all cases and increase of HSD3B1 mRNA expression in 5. Conclusion: In the present study, we successfully cloned two stable variants that show ER activity depending on androgen metabolites. Investigation of these cell lines suggested that the increased function of 3β-HSD type 1 and reduced function of AR contribute to AI resistance by enhancing the androgen metabolite-dependent growth and reducing the inhibitory effect of androgens. Our data of clinical samples suggest that this mechanism also acts as an AI-resistance in clinical breast cancer in some cases. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-04-17.
GSTT1 and CYP2E1 polymorphisms and trihalomethanes in drinking water: effect on childhood leukemia.
Authors: Claire Infante-Rivard, Devendra Amre, Daniel Sinnett
Journal: Environmental Health Perspectives (2002)

The purpose of the study was to determine whether the risk of childhood acute lymphoblastic leukemia (ALL) associated with drinking water disinfection by-products was modified in the presence of variants in genes involved in the metabolism of trihalomethanes (THMs). We included a subset of cases from a population-based case-control study in a case-only study to estimate the interaction odds ratios (IORs) between prenatal and postnatal exposure to THMs and polymorphisms in the GSTT1 and CYP2E1 genes. We compared cases with and without a given variant regarding their exposure to THMs using unconditional logistic regression. The IOR for a postnatal average of total THM above the 95th percentile with GSTT1 null genotype was 9.1 [95% confidence interval (95% CI), 1.4-57.8]. With CYP2E1 (variant G-1259C, known as the allele CYP2E1*5), the effect of exposure during pregnancy for an average exposure to total THM at or above the 75th percentile was 9.7 (95% CI, 1.1-86.0). These results contrast strongly with those from our case-control analysis, in which we considered the exposure to THMs only in relation with ALL, and observed no increase in risk or very moderate ones. The present preliminary study shows suggestive but imprecise results. We found no similar results in the literature, underscoring the need for other studies as well as the potential usefulness of combining exposure and relevant genetic information in such studies.
Endoscopic Electro-Transsection of a Duodenal Band
Authors: R. Ottenjann, J. Weingart
Journal: Endoscopy (1975)

Ligaments in the gastrointestinal tract are a rare disorder. There are several reports on so-called double pylorus with duodeno-gastric band in the recent literature. A case is presented where a duodenal band was diagnosed during endoscopy and successfully treated without complications by duodenoscopic electro-transsection.
TCT-647 Value Of High-Density Lipoprotein Cholesterol In Predicting Future Cardiovascular Events Of Patients With Low-Density Lipoprotein Cholesterol At The Time Of Percutaneous Coronary Intervention
Authors: Gabriel Sardi, Rebecca Torguson, Hironori Kitabata, Joshua Loh, Salem Badr, William Suddath, Lowell Satler, Kenneth Kent, Augusto Pichard, Bryan Brewer, Ron Waksman
Journal: Journal of the American College of Cardiology (2012)
Genetic Variants in the PI3K/PTEN/AKT/mTOR Pathway Predict Head and Neck Cancer Patient Second Primary Tumor/Recurrence Risk and Response to Retinoid Chemoprevention
Authors: Michelle A.T. Hildebrandt, Scott M. Lippman, Carol J. Etzel, Edward Kim, J. Jack Lee, Fadlo R. Khuri, Margaret R. Spitz, Reuben Lotan, Waun Ki Hong, Xifeng Wu
Journal: Clinical Cancer Research (2012)

The development of second primary tumors (SPT) or recurrence alters prognosis for curatively treated head and neck squamous cell carcinoma (HNSCC) patients. The 13-cis-Retinoic acid (13-cRA) has been tested as a chemoprevention agent in clinical trials with mixed results. Therefore, we investigated whether genetic variants in the PI3K/PTEN/AKT/mTOR pathway could serve as biomarkers to identify which patients are at high risk of an SPT/recurrence, while also predicting response to 13-cRA chemoprevention.A total of 137 pathway single-nucleotide polymorphisms were genotyped in 440 patients from the Retinoid Head and Neck Second Primary Trial and assessed for SPT/recurrence risk and response to 13-cRA. Risk models were created based on epidemiology, clinical, and genetic data.Twenty-two genetic loci were associated with increased SPT/recurrence risk, with six also being associated with a significant benefit following chemoprevention. Combined analysis of these high-risk/high-benefit loci identified a significant (P = 1.54 × 10(-4)) dose-response relationship for SPT/recurrence risk, with patients carrying four to five high-risk genotypes having a 3.76-fold [95% Confidence Interval (CI), 1.87-7.57] increase in risk in the placebo group (n = 215). Patients carrying four to five high-risk loci showed the most benefit from 13-cRA chemoprevention, with a 73% reduction in SPT/recurrence (95% CI, 0.13-0.58) compared with those with the same number of high-risk genotypes who were randomized to receive placebo. Incorporation of these loci into a risk model significantly improved the discriminatory ability over models with epidemiology, clinical, and previously identified genetic variables.These results show that loci within this important pathway could identify individuals with a high-risk/high-benefit profile and are a step toward personalized chemoprevention for HNSCC patients.
Points from Letters: Disposable Linen for Bed-ridden Patients
Authors: J. Shaw
Journal: BMJ (1967)

example-English doctors.Surely the sen- sible thing for the Government of Pakistan would be to encourage these doctors to return to Pakistan, and if necessary " exploit" the services of their wives.England may suffer by losing these qualified people, but surely Pakistan's need of their services is even greater.The B.M.A. has played a great part in medical history, and surely its sister associa- tion, with Professor Hamid Ali Khan in the chair, could follow its example in this way and attempt the abolition of the reverse "'colour bar."I hope many of my fellow- countrymen will pluck up courage to fight this absurd undemocratic law and injustice.I also must remain anonymous.-Iam, etc., ANON.
Association of Serum Hepatitis With One Lot of Dried Irradiated Pooled Plasma
Authors: Richard D. Aach
Journal: JAMA (1965)

During 1961 and 1962 the incidence of serum hepatitis was determined among recipients of one lot of dried irradiated pooled plasma suspected of being icterogenic. A total of 106 patients was found to have received plasma when portions of the suspect lot were available at 20 hospitals in 13 states. Serum hepatitis developed in 12 of the recipients 70 to 146 days after receiving plasma; four died. The investigation was hindered by poor recording practices. Accurate records concerning the administration of all potentially icterogenic blood products are clearly needed. Now that other effective, safe, and more economical plasma volume expanders are available, the use of irradiated pooled plasma no longer seems warranted.
Agranulocytosis &amp; Para-amino-benzene Sulphonamide
Authors: C. J. Young
Journal: BMJ (1937)

Kracke and Parker (1933, 1934) presented evidence.that agranulocytosis might be caused by certain drugs, notably amidopyrine, phenacetin, certain gold salts, and arsphena- mine.They pointed out that structurally these drugs possess in common the benzene ring with an attached NH2 or amine group, which increases the ease of oxidation.A consideration of the formula of sulphanila- mide suggested to us the possibility that this drug might NH2.SO, NH, Para-aminobenzene sulphonamide.also be capable of producing agranulocytosis.The matter aopeared to be one of importance for various reasons.First, if the drug reduced the polymorph concentration in the blood in cases of infection against which it was therapeutically ineffective, it might affect unfavourably the course of the disease.Secondly, sulphanilamide is used in acute infections which are not infrequently fatal, and where the latter outcome resulted from agranulocytosis this might readily escape observation.Thirdly, the drug is available to the general public and has received con- siderable publicity in the lay press.It was decided, therefore, to make observations on the leucocytes in sulphanilamide-treated patients.Complete agranulocytosis with fatal result occurred in the second case investigated.While the possibilities are obvious, it naturally cannot be determined whether this occurrence was or was not due to the administration of this drug.
Abstract 5158: Differentiation of glioblastoma stem-like cells induced by retinoic acid
Authors: Mingyao Ying, YingYing Sang, Bachchu Lal, Peng Sun, John Laterra, Shuli Xia
Journal: Cancer Research (2010)

Abstract We investigated the molecular and cellular responses of glioblastoma stem-like cells (GBM-SCs) to all-trans retinoic acid (RA)-induced differentiation. Four GBM-SC lines were used. Under neurosphere culture conditions, GBM-SCs grow as non-adherent neurospheres. RA (10 μmol/l) treatment for 48 h induced cells to adhere to culture surfaces and generate processes. RA inhibited G1/G0 to S transition, decreased cyclin D1 expression (50%) and increased p27 expression (2-fold). Immunofluorescence staining, western blot and flow cytometry analyses showed that RA induced the expression of differentiation markers Tuj1 and GFAP and inhibited nestin expression. RA treatment reduced the number of cells expressing CD133 from 44% to 10%. We measured the effects of RA on neurosphere number and size. RA treatment dramatically decreased (∼90%) the number of neurospheres &amp;gt; 50 um diameter. Clonogenic assay showed that RA reduced the colony formation ability of GBM-SCs in soft agar. Microarray analysis was performed to determine the global gene expression profile of RA-induced GBM-SC differentiation. Data were analyzed using Significance Analysis of Microarrays (SAM) and the false discovery rate was set at 20%. Approximately 350 genes were altered after RA treatment for 48h; ∼20% were down-regulated and 80% were up-regulated. We selected 18 candidates and validated with real-time PCR. All 18 candidates exhibited the same pattern of up- or down-regulation by RA. Western blot analysis for some candidate gene products also confirmed the alteration by RA at the protein level. A web-based (portal.genego.com) molecular pathway analysis of RA-induced gene expression profiling identified several pathways altered during RA-induced differentiation process. The most prominent of them was Notch signaling. Notch pathway members Delta-like 1 (DLL1), Notch 1, NCID, NEXT and Notch 1 precursor were found to be down-regulated by RA. Only Delta-like 4 (DLL4) was up-regulated by RA. We also found that cyclin D, cyclin D1, PP2A and SMAD3, gene products involved in G1-S transition, were down-regulated by RA. This is consistence with our findings that RA induces cell cycle arrest. Numerous mechanisms involved in cell adhesion, cell-matrix interaction and cytoskeleton remodeling were also affected by RA. This analysis provides guidelines to further explore pathways and mechanisms during RA-induced GBM-SC differentiation. Our findings may be applicable to identify new molecular target applicable to differentiation therapies for glioblastomas. This will also stimulate the development of GBM stem cell based pre-clinical experimental models with the potential to improve mechanistic and pre-clinical therapeutic research. 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 5158.
Abstract 2734: Residual embryonic cells as precursors of a Barrett's-like metaplasia.
Authors: Xia Wang
Journal: Cancer Research (2013)

Abstract Barrett's esophagus is an intestine-like metaplasia and precursor of esophageal adenocarcinoma. Trig- gered by gastroesophageal reflux disease, the origin of this metaplasia remains unknown. p63-deficient mice, which lack squamous epithelia, may model acid-reflux damage. We show here that p63 null embryos rapidly develop intestine-like metaplasia with gene expression profiles similar to Barrett's metaplasia. We track its source to a unique embry- onic epithelium that is normally undermined and re- placed by p63-expressing cells. Significantly, we show that a discrete population of these embryonic cells persists in adult mice and humans at the squa- mocolumnar junction, the source of Barrett's meta- plasia. We show that upon programmed damage to the squamous epithelium, these embryonic cells migrate toward adjacent, specialized squamous cells in a process that may recapitulate early Barrett's. Our findings suggest that certain precancerous lesions, such as Barrett's, initiate not from genetic alterations but from competitive interactions between cell lineages driven by opportunity. Citation Format: Xia Wang. Residual embryonic cells as precursors of a Barrett's-like metaplasia. [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 2734. doi:10.1158/1538-7445.AM2013-2734
Traumatic brain injury is more widespread than previously estimated
Authors: B. Roehr
Journal: BMJ (2012)

An estimated 54-60 million people worldwide sustain a traumatic brain injury every year, a new study indicates, about six times the previous estimate.1 Between 2.2 million and 3.6 million of the injuries are moderate to severe. 

Traumatic brain injury is the leading cause of long term disability among children and young adults and cost an estimated $406bn (£250bn; €315bn) in the United States in 2000. It is projected to become the third largest cause of disease burden worldwide by 2020.

Earlier projections focused on acute injury where medical attention …
Contempo: Ethical Issues of Human Embryos Research and Physician-Assisted Suicide
Authors: Peter Goodwin
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Dr Pellegrino<sup>1</sup>writes that the<i>Oregonian</i>newspaper was an "enthusiastic promoter" of Oregon's Death With Dignity Act,<sup>2</sup>and refers to the December 4, 1994, edition. In fact, the<i>Oregonian</i>was implacably opposed to the ballot measure, as evidenced by two strongly worded editorials (<i>Oregonian</i>. October 20, 1994, and November 2, 1994, metro section), by its unequivocal "no" vote recommendation on ballot measure 16 (<i>Oregonian</i>. November 3, 1994, metro section), and by many feature articles. He writes, "Pharmacists...would have to fill prescriptions." The law specifically states that no health care provider shall be under any duty, whether by contract, by statute, or by any other legal requirement, to participate in the provision to a qualified patient of medication to end his or her life. If Pellegrino has read the law, he will know that choice and voluntary participation are two of its cornerstones. I am as
Research and Patient Care
Authors: Hans H. Hecht
Journal: JAMA (1971)

There are two reasons why today we may wish to cast a brief glance both backward and forward: this is the 40th Frank Billings Lecture of the American Medical Association—an anniversary of sorts of lectures delivered annually by a succession of eminent American clinicians and investigators. The speaker today has no such claim, but he is the first to have been from an institution and department that owes its existence to Frank Billings and whose clinical facilities carry his name, the Billings Hospital. This is actually the oldest of 11 divisions of the University of Chicago Hospitals and Clinics complex on the campus of the university. It was named after Billings' uncle, Albert Merritt Billings, who was the founder and organizer of the Peoples Gas Company in Chicago. <h3>Frank Billings, an Architect of Early American Medical Education</h3> Frank Billings was born in 1854 in Highland, Iowa County, southwestern Wisconsin, the
125I-insulin binding to cultured human lymphocytes. Initial localization and fate of hormone determined by quantitative electron microscopic autoradiography.
Authors: J L Carpentier, P Gorden, M Amherdt, E Van Obberghen, C R Kahn, L Orci
Journal: Journal of Clinical Investigation (1978)

Morphologic and biochemical studies indicate that the initial action of insulin is binding to a cell surface receptor. Whether further translocation of the hormone, or a product of the hormone, occurs is unclear and has not been investigated by direct means. To determine the fate of 125I-insulin bound to its receptor, we have examined the distribution of radioactivity by quantitative electron microscopic autoradiography. Cultured lymphocytes of the IM-9 cell line were incubated with 0.1 nM 125I-insulin at 15 degrees and 37 degreesC for incubation periods extending from 2 to 90 min. At 15 degreesC, grains localize to the plasma membane and there is no translocation as a function of time. At 37 degreesC, grains predominantly localize to the plasma membrane but there is a small shift in distribution to a distance of 300-700 nm from the plasma membrane. This small additional band component of irradiation extends to approximately to10--15% of the cell radius. When a morphometric analysis is applied to grains extending 300 nm and beyond from the plasma membrane, we find no preferential localization to any intracellular organelle. We interpret these data to indicate that in the cultured lymphocyte, labeled insulin initially localizes to the plasma membrane but as fuanction of time and increasing temperature there is a small but definite translocation of the hormone or a product of the hormone to a hihgly limited aea of the cell periphery.
Doctors in India prosecuted for sex determination, but few convicted
Authors: Ganapati Mudur
Journal: BMJ (2006)

Pressure from the medical community is obstructing action against doctors in India involved in illegal sex determination and selective abortion of female fetuses, government officials said last week, echoing concerns expressed by health activists.

More than 300 doctors have been prosecuted in India for violating a 12 year old law that prohibits doctors from disclosing the sex of a fetus to parents, but only four have been convicted, officials said at a conference on sex selection technologies in New Delhi.

Birth registration figures show …
Regulation of CXCR4 conformation by the small GTPase Rac1: implications for HIV infection
Authors: Younes Zoughlami, Carlijn Voermans, Kim Brussen, Karel A. van Dort, Neeltje A. Kootstra, David Maussang, Martine J. Smit, Peter L. Hordijk, Paula B. van Hennik
Journal: Blood (2012)
972-104 Diagnostic Ability of a Single Admission Value of Serum Myoglobin, Troponin-T and CK-MB in Acute Myocardial Infarction Patients
Authors: Birgit Jurlander, Peter Clemmensen, Soren Galatius Ipon Jensen, Galen S. Wagner, Peer Grande
Journal: Journal of the American College of Cardiology (1995)
So what have data standards ever done for us? The view from metabolomics
Authors: Julian L Griffin, Christoph Steinbeck
Journal: Genome Medicine (2010)

The standardization of reporting of data promises to revolutionize biology by allowing community access to data generated in laboratories across the globe. This approach has already influenced genomics and transcriptomics. Projects that have previously been viewed as being too big to implement can now be distributed across multiple sites. There are now public databases for gene sequences, transcriptomic profiling and proteomic experiments. However, progress in the metabolomic community has seemed to falter recently, and whereas there are ontologies to describe the metadata for metabolomics there are still no central repositories for the datasets themselves. Here, we examine some of the challenges and potential benefits of further efforts towards data standardization in metabolomics and metabonomics.
Impact of Quality Improvement Efforts on Race and Sex Disparities in Hemodialysis
Authors: Ashwini R. Sehgal
Journal: JAMA (2003)

By improving the process of care, quality improvement efforts have the potential to reduce race and sex disparities. However, little is known about whether reductions actually occur. National quality improvement activities targeting hemodialysis patients provide an opportunity to examine this issue.To determine the effect of quality improvement efforts on race and sex disparities among hemodialysis patients.Longitudinal study of 58 700 randomly selected hemodialysis patients from throughout the United States in 1993 through 2000.Medicare-funded quality improvement project involving monitoring of patient outcomes, feedback of performance data, and education of clinicians at dialysis centers.Changes in hemodialysis dose (Kt/V), anemia management (hemoglobin level), and nutritional status (albumin level).The proportion of all patients with an adequate hemodialysis dose increased 2-fold. In 1993, 46% of white patients and 36% of black patients received an adequate hemodialysis dose compared with 2000 when the proportions were 87% and 84%, respectively. Thus, the gap between white and black patients decreased from 10% to 3% (P<.001). The gap between female and male patients decreased from 23% to 9% over the same period (P =.008). The proportion of all patients with adequate hemoglobin levels increased 3-fold. The proportion of all patients with adequate albumin levels remained unchanged. Race and sex disparities in anemia management and nutritional status did not change significantly.Quality improvement efforts have a variable impact on race and sex disparities in health outcomes. Further work is needed to determine how quality improvement methods can be targeted to reduce health disparities.