tbuckley/cabot-search huggingface dataset:
A Haplotype Analysis of <i>HER-2</i> Gene Polymorphisms: Association with Breast Cancer Risk, HER-2 Protein Expression in the Tumor, and Disease Recurrence in Korea
Authors: Wonshik Han, Daehee Kang, Jong Eun Lee, In Ae Park, Ji-Yeob Choi, Kyung-Mu Lee, Ji Yeon Bae, Sook Kim, Eun-Soon Shin, Jeong Eon Lee, Hyuk-Jae Shin, Seok Won Kim, Sung-Won Kim, Dong-Young Noh
Journal: Clinical Cancer Research (2005)

Abstract Purpose: A single-nucleotide polymorphism (SNP) in codon 655 of HER-2 has been extensively studied with inconclusive results. The purpose of this study was to investigate the association between common variants of HER-2 and breast cancer risk, HER-2 expression, and survival using a haplotype-based stepwise approach. Experimental Design: Twenty-nine SNPs listed in the National Center for Biotechnology Information database were screened to identify novel polymorphisms of HER-2 gene in 90 healthy Korean women. Six of 29 SNPs were polymorphic and had greater than 10% of minor allele frequencies. Using these six SNPs, linkage disequilibrium and haplotype patterns were characterized. We tested association between the haplotypes and breast cancer in a large case–control study (n = 1,039 cases and 995 controls). Six-hundred two breast cancer patients with follow-up at least 24 months were analyzed for outcome in relation to haplotype. Expression of HER-2 protein was determined by immunohistochemistry in 1,094 cases of invasive breast cancer. Results: All six SNPs showed a strong linkage disequilibrium pattern and were considered to belong to one haplotype block. Two haplotype-tagging SNPs (I655V and P1170A) for three common haplotypes (&amp;gt;5%) were genotyped in cases and controls. The haplotypes and individual SNPs were not associated with breast cancer risk. In patients with at least one copy of haplotype I (the most common haplotype), HER-2 expression was 1.5 times higher (P = 0.009) and the prognosis was worse (P = 0.032) compared with patients without having that haplotype. Conclusions: Our results suggest that the currently identified genetic polymorphisms of HER-2 are not associated with an increased risk of breast cancer in Korean women, whereas one haplotype does affect protein expression of the tumor and disease outcome.
Differential Compartmentalization and Distinct Functions of GABAB Receptor Variants
Authors: Réjan Vigot, Samuel Barbieri, Hans Bräuner-Osborne, Rostislav Turecek, Ryuichi Shigemoto, Yan-Ping Zhang, Rafael Luján, Laura H. Jacobson, Barbara Biermann, Jean-Marc Fritschy, Claire-Marie Vacher, Matthias Müller, Gilles Sansig, Nicole Guetg, John F. Cryan, Klemens Kaupmann, Martin Gassmann, Thomas G. Oertner, Bernhard Bettler
Journal: Neuron (2006)
Urinary Androgen Excretion and the Etiology of Breast Cancer&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: R. D. Bulbrook
Journal: JNCI Journal of the National Cancer Institute (1972)

It is suggested that most women who develop breast cancer excrete subnormal amounts of androgen and estrogen metabolites before diagnosis and that the estrogens are not of major importance in the etiology of the disease in this group. At diagnosis, there is a rapid recurrence rate after mastectomy and, generally, a poor response to endocrine ablation. In a few patients, androgen and estrogen excretions are above the normal range and estrogens may be an important etiological factor. These patients have hormone-responsive tumors.
Economics of Preoperative Radiotherapy With Total Mesorectal Excision: What Can We Learn From the Dutch Experience?
Authors: Marko Simunovic, Amiram Gafni, Mark Levine
Journal: Journal of Clinical Oncology (2003)

Patients undergoing rectal cancer surgery may also receive radiation therapy to reduce local tumor recurrence and improve survival [1,2]. In parts of Europe, a 5-day course of preoperative radiotherapy (PRT) alone is recommended for most patients, while other European and North American countries utilize a 5-week course of postoperative chemoradiotherapy for patients with stage II or III tumors [3]. Total mesorectal excision (TME) stresses sharp and complete dissection of the mesorectum, the lymph node– bearing portion of the rectum [4]. Compared with traditional blunt rectal cancer surgery, TME seems to lead to superior rates of sphincter preservation, local tumor control, and survival [4]. The Dutch Colorectal Cancer Group has conducted a randomized trial that compared outcomes of TME, with and without PRT, for patients with resectable rectal cancer [5]. At a median follow-up of 2 years, local recurrence rates were 2.4% and 8.2% for radiated and nonradiated patients, respectively, with no significant difference in overall survival [5]. These results may change with further follow-up. In this issue of the Journal of Clinical Oncology, van den
Separation Reactions of Married Women
Authors: CHESTER A. PEARLMAN
Journal: American Journal of Psychiatry (1970)

The author describes the types of reactions to periodic separation of 485 married psychiatric outpatients. The data support Bowlby's hypothesis that the separation reaction is a psychobiological response pattern that has different implications according to the characterological development of the individual. Some criteria for successful adjustment to separation are described, and a therapeutic method to aid the development of separation tolerance is outlined. The nature and resolution of marital problems arising from separation are also discussed.
Methylisothiazolinone in rinse-off products causes allergic contact dermatitis: a repeated open-application study
Authors: K. Yazar, M.D. Lundov, A. Faurschou, M. Matura, A. Boman, J.D. Johansen, C. Lidén
Journal: British Journal of Dermatology (2015)

In recent years, the prevalence of contact allergy to the preservative methylisothiazolinone (MI) has increased dramatically. Cosmetic products are one of the major sources of exposure.To examine whether allowed concentrations of MI in cosmetic rinse-off products have the potential to cause allergic contact dermatitis.Nineteen MI-allergic subjects and 19 controls without MI allergy applied two liquid hand soaps five times per day on areas of 5 × 10 cm(2) on the ventral side of their forearms. One soap contained 100 ppm MI, the maximum allowed concentration in cosmetics, and was used by 10 allergic subjects and all controls. Another liquid soap with 50 ppm MI was used by nine allergic subjects. As the negative control, all subjects used a similar soap that did not contain MI. The repeated open applications proceeded until a positive reaction occurred or up to 21 days. The study was conducted in a randomized and blinded fashion.Ten out of 10 MI-allergic subjects developed positive reactions to the soap with 100 ppm and seven out of nine reacted to the 50 ppm soap, while none of the 19 controls had a positive reaction during 21 days of application. No reactivity was seen to the soap without MI. The difference in reactivity to MI between MI-allergic subjects and controls was statistically significant (Fisher's exact test, P ˂ 0.0001).Rinse-off products preserved with 50 ppm MI or more are not safe for consumers. No safe level has yet been identified.
The cutaneous porphyrias: a review
Authors: None MURPHY
Journal: British Journal of Dermatology (1999)

Many patients with cutaneous porphyria have curable or controllable disease; untreated porphyria may prove fatal. The genetic defects and mechanisms underlying porphyria are steadily being delineated, treatments have become more appropriate and genetic counselling is now more accurate. A summary of the basic diagnostic features, management and recent advances in the cutaneous porphyrias is presented, based on a workshop held by the British Photodermatology Group.
An Address on Some Effects of the Climate of Torquay
Authors: C. R. Hall
Journal: BMJ (1878)

branch of the Samaritan Hospital, entered into a curious calculation, and showed the total gain of life of the 373 survivors of my first 500 operations to be "1 IO,817 years of average healthy life, instead of the 1,492 years of miserable endurance which they might have passed be- fore death without operation".Of the 400 patients operated on since the 500, 306 are cured, making the total recoveries 679.Multiplying this number by 29 years, the average estimated gain of each patient, the total gain amounts to I9,69I years.I submitted the basis of Lord Selborne's calculation to Dr. William Farr, thinking possibly there might be some fallacy which I had not detected.Dr. Farr confirmed its complete accuracy, and it is a very simple piece of multiplication.The average age of the patients was as nearly as possible thirty-eight years.At this period, the Carlisle Tables assign, as the expectation of life for a healthy woman in this country, twenty-nine years ; so that one has simply to multiply the number of survivors by twenty-nine.Had the women not been operated upon, it would be a very liberal allowance to estimate their average expectation at four years; and Lord Selborne, speaking of the addition to life to each of the women successfully operated upon, has calculated twenty-five years as clear or absolute gain.He said: " Instead of the four years of declining health and hopeless misery which these women would have had to anticipate, not only those four years, but twenty-five years, which upon the average had been wholly saved to them, were years of restored health, usefulness, and happiness."PATHOLOGICAL MEMORANDA. OBLITERATIVE ENDARTERITIS.THE interesting article on obliterative endarteritis in the JOURNAL of June 29th shows a disposition to abandon the pathological signifi- cance of that form of syphilitic arteritis with which the name of Heubner more especially is associated.Whatever be the final outcome of the observations of Friedlander, Koster, and Baumgarten, there seems to be reason, at the present juncture, to avoid a too ready
Primate erythrocyte-immune complex-clearing mechanism.
Authors: J B Cornacoff, L A Hebert, W L Smead, M E VanAman, D J Birmingham, F J Waxman
Journal: Journal of Clinical Investigation (1983)

Previous in vitro studies have shown that immune complexes (IC) that fix complement can bind to the C3b receptor on primate erythrocytes. The in vivo function of this erythrocyte receptor, however, is unknown. This study was undertaken to determine whether the binding of IC to erythrocytes in vivo might play a role in the removal of IC from the circulation. Baboons and rhesus monkeys were prepared with a catheter in the ascending aorta to infuse IC and in the abdominal aorta, renal, hepatic, and portal veins to monitor changes in binding and clearance of IC across kidney, liver, and spleen + gut, respectively. Autologous 51Cr-labeled erythrocytes were infused intravenously and allowed to equilibrate. Preformed IC (125I-labeled bovine serum albumin [BSA] rabbit anti-BSA) were then infused into the ascending aorta at a constant rate for 120 s. Blood samples were drawn at frequent intervals for 30 min from all catheters below the IC injection site. Each blood sample was then centrifuged on percoll to separate IC bound to erythrocytes from IC in plasma or bound to buffy coat cells. This resulted in an "erythrocyte fraction" beneath the percoll that contained the IC bound to erythrocytes, and a "plasma/buffy coat fraction" above the percoll that contained the IC in plasma and IC bound to buffy coat cells. Analysis of these data showed that the majority of the IC infused into the circulation rapidly became bound to erythrocytes. However, by 5 min after beginning the IC infusion, most of this IC load had been removed from the erythrocytes as they traversed the liver. In contrast, IC on erythrocytes did not deposit in kidney. The IC-bearing erythrocytes themselves were not trapped or detained by any organ. IC in the plasma/buffy coat fraction of blood were removed from the circulation but at a relatively low rate and almost entirely by the liver. These findings suggest that primate erythrocytes intercept large complement-fixing IC in the circulation causing the IC to adhere to the erythrocyte until th e IC-bearing erythrocyte traverses liver where the IC is deposited, and the erythrocyte is returned to the circulation. This primate erythrocyte-IC-clearing mechanism may be important in the protection against diseases mediated by deposition of circulating IC.
Halting pro-survival autophagy by TGFβ inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients
Authors: M A Frassanito, K De Veirman, V Desantis, L Di Marzo, D Vergara, S Ruggieri, T Annese, B Nico, E Menu, I Catacchio, R Ria, V Racanelli, M Maffia, E Angelucci, D Derudas, R Fumarulo, F Dammacco, D Ribatti, K Vanderkerken, A Vacca
Journal: Leukemia (2015)
HDAC Inhibitors Potentiate the Activity of the BCR/ABL Kinase Inhibitor KW-2449 in Imatinib-Sensitive or -Resistant BCR/ABL+ Leukemia Cells <i>In Vitro</i> and <i>In Vivo</i>
Authors: Tri Nguyen, Yun Dai, Elisa Attkisson, Lora Kramer, Nicholas Jordan, Nguyen Nguyen, Nikhil Kolluri, Markus Muschen, Steven Grant
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The purpose of this study was to determine whether histone deacetylase (HDAC) inhibitors (HDACI) such as vorinostat or entinostat (SNDX-275) could increase the lethality of the dual Bcr/Abl-Aurora kinase inhibitor KW-2449 in various Bcr/Abl+ human leukemia cells, including those resistant to imatinib mesylate (IM). Experimental Design: Bcr/Abl+ chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) cells, including those resistant to IM (T315I, E255K), were exposed to KW-2449 in the presence or absence of vorinostat or SNDX-275, after which apoptosis and effects on signaling pathways were examined. In vivo studies combining HDACIs and KW2449 were carried out by using a systemic IM-resistant ALL xenograft model. Results: Coadministration of HDACIs synergistically increased KW-2449 lethality in vitro in multiple CML and Ph+ ALL cell types including human IM resistant cells (e.g., BV-173/E255K and Adult/T315I). Combined treatment resulted in inactivation of Bcr/Abl and downstream targets (e.g., STAT5 and CRKL), as well as increased reactive oxygen species (ROS) generation and DNA damage (γH2A.X). The latter events and cell death were significantly attenuated by free radical scavengers (TBAP). Increased lethality was also observed in primary CD34+ cells from patients with CML, but not in normal CD34+ cells. Finally, minimally active vorinostat or SNDX275 doses markedly increased KW2449 antitumor effects and significantly prolonged the survival of murine xenografts bearing IM-resistant ALL cells (BV173/E255K). Conclusions: HDACIs increase KW-2449 lethality in Bcr/Abl+ cells in association with inhibition of Bcr/Abl, generation of ROS, and induction of DNA damage. This strategy preferentially targets primary Bcr/Abl+ hematopoietic cells and exhibits enhanced in vivo activity. Combining KW-2449 with HDACIs warrants attention in IM-resistant Bcr/Abl+ leukemias. Clin Cancer Res; 17(10); 3219–32. ©2011 AACR.
Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis
Authors: Katey J. Rayner, Frederick J. Sheedy, Christine C. Esau, Farah N. Hussain, Ryan E. Temel, Saj Parathath, Janine M. van Gils, Alistair J. Rayner, Aaron N. Chang, Yajaira Suarez, Carlos Fernandez-Hernando, Edward A. Fisher, Kathryn J. Moore
Journal: Journal of Clinical Investigation (2011)

Plasma HDL levels have a protective role in atherosclerosis, yet clinical therapies to raise HDL levels have remained elusive. Recent advances in the understanding of lipid metabolism have revealed that miR-33, an intronic microRNA located within the SREBF2 gene, suppresses expression of the cholesterol transporter ABC transporter A1 (ABCA1) and lowers HDL levels. Conversely, mechanisms that inhibit miR-33 increase ABCA1 and circulating HDL levels, suggesting that antagonism of miR-33 may be atheroprotective. As the regression of atherosclerosis is clinically desirable, we assessed the impact of miR-33 inhibition in mice deficient for the LDL receptor (Ldlr–/– mice), with established atherosclerotic plaques. Mice treated with anti-miR33 for 4 weeks showed an increase in circulating HDL levels and enhanced reverse cholesterol transport to the plasma, liver, and feces. Consistent with this, anti-miR33–treated mice showed reductions in plaque size and lipid content, increased markers of plaque stability, and decreased inflammatory gene expression. Notably, in addition to raising ABCA1 levels in the liver, anti-miR33 oligonucleotides directly targeted the plaque macrophages, in which they enhanced ABCA1 expression and cholesterol removal. These studies establish that raising HDL levels by anti-miR33 oligonucleotide treatment promotes reverse cholesterol transport and atherosclerosis regression and suggest that it may be a promising strategy to treat atherosclerotic vascular disease.
Angiotensin II receptor subtypes on adrenal adenoma in primary hyperaldosteronism.
Authors: M D Cook, M I Phillips, V I Cook, B Kimura, C S Wilcox
Journal: Journal of the American Society of Nephrology (1993)

Patients with an aldosterone-producing adenoma (APA) characteristically fail to show an increase in plasma aldosterone (PA) concentration with maneuvers that increase angiotensin II (Ang II), yet they retain a brisk response of PA to adrenocorticotrophic hormone. Therefore, adrenal Ang II receptor binding was characterized in a patient with APA who had a blocked PA response to Ang II infusion before adrenalectomy. The binding of [125I]Sar1,IIe5-Ang II in adrenal gland and tumor was fully displaced by excess Ang II. In the tumor, 98% of [125I]Sar1,IIe5-Ang II binding was displaced by the AT, receptor antagonist losartan, yet only 5% was displaced by the AT2 receptor antagonist PD-123,319. Autoradiography of the adrenal gland itself showed a predominance of AT1 receptors in the cortex and AT2 receptors in the medulla. The tumor showed a predominance of AT1 receptors, but there was some evidence of a limited population of AT2 receptors. The tumor and adjacent adrenal contained high concentrations of Ang II. In conclusion, a defect in Ang II-stimulated aldosterone secretion in APA occurs despite high concentrations of Ang II in the adrenal and the presence of specific, high-affinity Ang II receptor binding sites.
Ambulatory blood pressure in children with obstructive sleep apnoea: a community based study
Authors: A M Li, C T Au, R Y T Sung, C Ho, P C Ng, T F Fok, Y K Wing
Journal: Thorax (2008)

<h3>Background:</h3> Childhood obstructive sleep apnoea (OSA) is increasingly being recognised. Its effects on blood pressure (BP) elevation and hypertension are still controversial. <h3>Objective:</h3> To evaluate the association between OSA and ambulatory BP in children. <h3>Methods:</h3> Children aged 6–13 years from randomly selected schools were invited to undergo overnight sleep study and ambulatory BP monitoring after completing a validated OSA questionnaire. OSA was diagnosed if the obstructive apnoea–hypopnoea index (AHI) was &gt;1, and normal controls had AHI &lt;1 and snoring &lt;3 nights per week. Children with OSA were subdivided into a mild group (AHI 1–5) and moderate to severe group (AHI &gt;5). <h3>Results:</h3> 306 subjects had valid sleep and daytime BP data. Children with OSA had significantly higher BP than normal healthy children during both sleep and wakefulness. BP levels increased with the severity of OSA, and children with moderate to severe disease (AHI &gt;5) were at significantly higher risk for nocturnal systolic (OR 3.9 (95% CI 1.4 to 10.5)) and diastolic (OR 3.3 (95% CI 1.4 to 8.1)) hypertension. Multiple linear regression revealed a significant association between oxygen desaturation index and AHI with daytime and nocturnal BP, respectively, independent of obesity. <h3>Conclusions:</h3> OSA was associated with elevated daytime and nocturnal BP, and is an independent predictor of nocturnal hypertension. This has important clinical implications as childhood elevated BP predicts future cardiovascular risks. Future studies should examine the effect of therapy for OSA on changes in BP.
Provision and Discussion of Survivorship Care Plans Among Cancer Survivors: Results of a Nationally Representative Survey of Oncologists and Primary Care Physicians
Authors: Danielle Blanch-Hartigan, Laura P. Forsythe, Catherine M. Alfano, Tenbroeck Smith, Larissa Nekhlyudov, Patricia A. Ganz, Julia H. Rowland
Journal: Journal of Clinical Oncology (2014)

Purpose Survivorship care planning should involve discussions between providers and cancer survivors to address survivors' needs and optimize adherence. We examined the frequency and factors associated with oncologists' and primary care physicians' (PCPs) reports of provision of written survivorship care plans (SCPs) and discussion of survivorship care recommendations with survivors. Methods A nationally representative sample of 1,130 oncologists and 1,020 PCPs was surveyed about survivorship care practices with survivors. Logistic regression models predicted multilevel factors associated with providing SCPs or discussing recommendations with survivors. Results Although a majority of oncologists (64%) reported always/almost always discussing survivorship care recommendations with survivors, fewer also discussed who survivors should see for cancer-related and other follow-up care (32%); fewer still also provided a written SCP to the survivor (&lt; 5%). Survivorship care recommendations and provider responsibility were not regularly discussed by PCPs and survivors (12%). Oncologists who reported detailed training about late and long-term effects of cancer were more likely to provide written SCPs (odds ratio [OR], 1.73; 95% CI, 1.22 to 2.44) and discuss survivorship care planning with survivors (OR, 2.02; 95% CI, 1.51 to 2.70). PCPs who received SCPs from oncologists were 9× more likely (95% CI, 5.74 to 14.82) to report survivorship discussions with survivors. Conclusion A minority of both PCPs and oncologists reported consistently discussing and providing SCPs to cancer survivors. Training and knowledge specific to survivorship care and coordinated care between PCPs and oncologists were associated with increased survivorship discussions with survivors. These nationally representative data provide a useful benchmark to assess implementation of new efforts to improve the follow-up care of survivors.