tbuckley/cabot-search huggingface dataset:
Diagnosis of Labia Metastasis by F-18 FDG PET and CT Fusion Imaging in Sarcoma Follow-up
Authors: L S Freudenberg, G Antoch, T Beyer, R Görges, J F Debatin, A Bockisch
Journal: Clinical Nuclear Medicine (2003)

A 32-year-old woman with a history of pelvic sarcoma underwent whole-body fluorine-18 fluorodeoxyglucose positron emission tomography (PET) and computed tomographic (CT) fusion imaging for restaging after primary surgery and adjuvant combined radiation and chemotherapy. Interpreting the PET images alone showed an area of focal tracer accumulation in the pelvic floor and was interpreted as being secondary to urine contamination. Image fusion with fully coregistered CT scans showed a localized site of increased uptake from a metastasis to the labia, which was confirmed by biopsy. The presented case illustrates the usefulness of combined PET/CT fusion imaging to overcome some pitfalls of PET imaging alone (eg, differentiating malignant tumor from pooling of tracer in the genitourinary tract or contamination).
Cardiovascular Risk and Sodium–Glucose Cotransporter 2 Inhibition in Type 2 Diabetes
Authors: Julie R. Ingelfinger, Clifford J. Rosen
Journal: New England Journal of Medicine (2015)

Patients with type 2 diabetes mellitus are at increased risk for incident cardiovascular and renal disease, conditions that increase the risk of death at a young age.1 Although intensive glycemic control has improved surrogate markers of cardiovascular risk in such patients, there has been no significant reduction in the risk of major adverse cardiovascular events (MACE), including nonfatal stroke or myocardial infarction and death from cardiovascular causes.2Now, in the results of the EMPA-REG OUTCOME trial published in this issue of the Journal, Zinman et al. report a decreased risk of death from all causes and cardiovascular causes among . . .
Tc-99m Sestamibi Uptake in a Patient With Gynecomastia
Authors: LAURA R. GELLETT, KIM D. FARMER, GILLIAN C. VIVIAN
Journal: Clinical Nuclear Medicine (1999)

A 56-year-old man with dialysis-dependent renal failure underwent parathyroid scintigraphy with Tc-99m MIBI. The results of laboratory tests showed biochemical hyperparathyroidism with hypercalcemia, hyperphosphatemia, increased alkaline phosphatase and parathormone levels. No active parathyroid adenomas were identified using either the MIBI washout or technetium subtraction techniques, which is not unusual in parathyroid hyperplasia. Bilateral homogeneous uptake was noted in both breasts. The patient had gynecomastia that coincided with the commencement of hormone replacement therapy to treat transfusion-dependent angiodysplasia of the colon.
AB0176 Association between Polymorphisms in Beta-Adducin and Sodium/Calcium Exchanger 1 and SLE with and without Nephritis
Authors: G.A. Ramirez, E.P. Bozzolo, N. Casamassima, C. Lanzani, P. Manunta, V. Canti, P. Rovere-Querini, M.G. Sabbadini, A.A. Manfredi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Genes involved in cytoskeletal assembly and water/electrolyte balance have been previously linked to hypertension, but recent evidences suggest a role also in the development of inflammation and autoimmunity [1-2]. Systemic Lupus Erythematosus is a prototypic multi-organ autoimmune disease, characterized by polymorphic clinical features and a complex polygenic background. Renal disease in SLE occurs in 40-70% of lupus patients and is responsible of an high burden of morbidity and mortality. Despite substantial efforts, less is known about the role of specific genetic factors in conferring susceptibility to SLE and its complications, including lupus nephritis (LN) [3]. <h3>Objectives</h3> With these premises we sought if an association between known hypertension-related polymorphisms and development of SLE and LN existed. <h3>Methods</h3> 106 patients (96 females, 10 males) diagnosed with SLE (n=51) or LN (n=55), 23 patients with Sjoegren9s Syndrome and 62 healthy controls were enrolled. Patients and controls were genotyped for polymorphisms in α-, β- and γ-adducin (ADD1,2,3 respectively), angiotensin converting enzyme, transient receptor potential cation channel-subfamily C, solute carrier family 8 (sodium-calcium exchanger) member 1 (SLC8A1), solute carrier family 24 (sodium/potassium/calcium exchanger) member 3, PKD2 calcium channel and PRKG1 kinase genes. <h3>Results</h3> Beta-adducin (ADD2) rs4984 CT heterozygosis was significantly more frequent in SLE patients than in LN patients (χ<sup>2</sup> =6.154; p=0.013). No patient had the ADD2 rs4984 TT genotype in accordance with a low prevalence of the ADD2 C1797T homozygosity in the population. Seven patients with SLE (n=3) or LN (n=4), but none of the control groups carried the AA variant of sodium/calcium exchanger 1 (SLC8A1) rs11893826 SNP (χ<sup>2</sup> =11.771; p=0.019). <h3>Conclusions</h3> Genes involved in the control of electrolyte/water balance and cytoskeletal plasticity could affect the pathogenic background of SLE/LN. Larger studies are required to confirm these data and attempt correlations between genetic data and specific clinical features. <h3>References</h3> Tintinger GR, et al., Drug Des Devel Ther, 2009 Kleinewietfeld M, et al., Nature, 2013 Ramos PS, et al., Semin Nephrol, 2010 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3378
CCURATE DETECTION OF SYMPTOMATIC AND ASYMPTOMATIC SINGLE ESSEL DISEASE BY QUANTITATIVE THALLIUM-201 PLANAR OR OMOGRAPHIC IMAGING VS EXERCISE ELECTROCARDIOGRAPHY (ECG)
Authors: osen Kiat, Jamshid Maddahi, Norma Daley, Enrique Ostrzega, en Van Train, Daniel Berman
Journal: Clinical Nuclear Medicine (1987)

Kiat, osen; Maddahi, Jamshid; Daley, Norma; Ostrzega, Enrique; Train, en Van; Berman, Daniel Author Information
Abstract P5-04-09: Squamous Cell Carcinoma Antigen 1 (SCCA1) Upregulation Causes Epithelial to Mesenchymal Transition (EMT) and Promotes Mammary Tumorigenesis
Authors: N Sheshadri, E Ullman, J Catanzaro, E Chen, W-X Zong
Journal: Cancer Research (2012)

Abstract SCCA1, a member of the family of serine protease inhibitors, was first identified as a serological marker for cervical cancer but has since been shown to be upregulated in several other cancers including lung, head and neck, liver, skin, and breast. SCCA1 is believed to protect cells from unscheduled cathepsin release and activation upon lysosomal injury. In order to understand the molecular role of SCCA in cancer, we ectopically expressed it in the immortalized yet non-tumorigenic mammary epithelial cell line MCF10A. Expression of SCCA1 impairs the efficiency of lysosomal as well as proteasomal protein degradation pathways. Transcriptional profiling of SCCA expressing cells by microarray demonstrates an altered gene expression pattern that resembles EMT. Phenotypically, SCCA1 expression leads to spindle shaped cell morphology, increased migratory potential, resistance to anoikis, and the ability to form colonies in soft agar. SCCA1-expressing MCF10A cells can form tumors when injected into the mammary fat pad of immune-compromised mice. Correlative to the transforming activity, SCCA1 expressing cells have enhanced Erk and Akt signaling pathways, and have bypassed the requirement of growth factors and hormones that are essential for proliferation of MCF10A cells. In a transgenic mouse model, where SCCA1 is conditionally expressed in mammary epithelial cells under the control of MMTV promoter, increased mammary gland ductal branching and hyperplasia are observed. These findings indicate a previously unknown role of SCCA1 in promoting EMT and tumorigenesis, possibly by inducing chronic misfolded protein stress that contributes to enhance tumor-promoting signaling. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-04-09.
Formaldehyde-Induced Hemolysis during Chronic Hemodialysis
Authors: Eugene P. Orringer, William D. Mattern
Journal: New England Journal of Medicine (1976)

We investigated an outbreak of hemolytic anemia among patients on hemodialysis shortly after the installation of a new water-filtration system. Using in vitro technics, we demonstrated that a water-soluble inhibitor of red-cell metabolism could easily be extracted from the intact filters. Subsequent experiments showed this toxic substance to be formaldehyde, a potent reducing agent whose mechanism of action involves conversion of NAD to NADH. This alteration of the redox state of the erythrocyte leads to inhibition of glycolysis at the level of glyceraldehyde 3-phosphate dehydrogenase and rapid decline in cellular energy (ATP) stores. Because formaldehyde is widely used as a preservative for dialysis equipment, the toxicity of this agent for red blood cells is of clinical importance. (N Engl J Med 294:1416–1420, 1976)
??ATE REVERSIBILITY OF THALLIUM-201 (T1-201) MYOCARDIAL TOMOGRAPHIC DEFECTS: AN ACCURATE MARKER OF MYOCARDIAL ??IABILITY.
Authors: Iosen Kiat, Jamshid Maddahi, Ling De Yang, Ken Van Train, Norma Daley, Christopher Wong, Daniel Berman
Journal: Clinical Nuclear Medicine (1987)

Kiat, Iosen; Maddahi, Jamshid; De Yang, Ling; Train, Ken Van; Daley, Norma; Wong, Christopher; Berman, Daniel Author Information
SP0063 Osteoporosis implications for primary care
Authors: C. Cooper
Journal: Annals of the Rheumatic Diseases (2013)

Recent decades have seen the emergence of a number of major pharmacological interventions to reduce the risk of osteoporotic fracture. The most commonly used agents in Europe are the bisphosphonates, alendronate, risedronate and ibandronate; raloxifene; strontium ranelate; and agents derived from parathyroid hormone. Hormone replacement therapy was also used widely until recently. All of these agents have been shown to reduce the risk of vertebral fracture; some have been shown to also reduce the risk of non-vertebral fractures, most notably fracture of the proximal femur. The availability of these agents, coupled with increasing awareness of osteoporosis, has led to increased demand for cost-effective management of patients with the disorder. There is, at present, no universally accepted policy for population screening in Europe to identify patients with osteoporosis or those at risk of fracture. In the absence of such a policy, patients tend to be identified opportunistically using a case-finding strategy on the basis of a previous fragility fracture or the presence of significant risk factors, for example, low body mass index, parental history of hip fracture, glucocorticoid therapy, current smoking or alcohol intake, and a variety of secondary causes of osteoporosis. On the basis of these clinical risk factors, it is possible to model the absolute risk of osteoporotic fracture, and ascertain the extent to which additional estimation of bone mineral density will assist in a therapeutic decision. A group convened by the World Health Organisation has constructed a potential algorithm for case finding, based on knowledge of the interactions of the clinical risk factors, age and BMD. When applied to the population of the United Kingdom, this management algorithm provides for the treatment of post-menopausal women with a previous fragility fracture without the need for a BMD test (as prior fracture is a very strong risk factor for future fracture and is largely independent of BMD). For the other risk factors, treatment can be delivered cost-effectively in women aged 65 years or more, but in women below this age, further stratification of risk is indicated with a BMD test. Among women with a parental history of hip fracture, treatment becomes worthwhile with a BMD T score of –1SD; for woman taking long term glucocorticoids, a T score threshold of –2SD is appropriate; while for weaker risk factors (secondary causes of osteoporosis, smoking and alcohol consumption), an appropriate threshold is a T score of -2.5 SD. A host of health economic analyses suggests that this approach meets widely used cost-effectiveness criteria for chronic disease prevention in the United Kingdom. It is hoped that its promulgation will result in improved management of this important chronic disorder in western populations. <h3>Disclosure of Interest</h3> None Declared
Abstract 786: Genomic and functional characterization identify different manifestations of p53 pathway in 17p13 deletion cases of multiple myeloma.
Authors: Phaik Ju Teoh, Junli Yan, Wee Joo Chng
Journal: Cancer Research (2013)

Abstract Multiple myeloma (MM) is an incurable hematologic malignancy. p53, being one of the most commonly mutated tumor suppressor gene in human cancer, is found to be wild type (WT) in almost 90% of MM. Nevertheless, the frequency of p53 abnormalities is more prevalent in the advanced stage of MM, suggesting its crucial role in the disease progression. Of paramount importance, hemizygous deletion of 17p13 (17p13(del)), which harbours the TP53 gene, has been identified in more than 30% of MM patients and is significantly associated with poor prognosis. To date, there is no conclusive evidence that p53 is the critical gene. Essentially, the integrity of p53 pathway in 17p13(del) cases remains obscure. This study utilized three human myeloma cell lines (HMCL) which harbour 17p13(del) encompassing TP53, as study models. Concurrently, HMCLs with various different p53 status (WT, mutation and null) were recruited as reference model. We have identified a spectrum of unique protein expression profile amongst cells with different p53 status upon induction of the pathway. Genotoxic and non-genotoxic stress confer an intact p53 pathway in WT/WT p53 cells; whereas, p53 mutant cells and p53 null cells demonstrated a defective p53 activity, indicating that functional p53 is exclusively required in triggering the downstream response. Using the WT/WT and the mutant/null profile as reference, the three 17p13(del) cell lines exhibited distinctive phenotypes. XG6, which have basal p53 expression half of that of the WT/WT cell line, displayed a partially compromised p53 pathway. Differentially, KMS18, which has a very low level of basal p53, and JJN3 which has a complete absence of basal p53, displayed a virtual abrogation of p53 response, as evidenced by defective transcriptional activities of p53 as well as resistance to growth arrest and apoptosis. Physiological investigations revealed that the remaining single copy of p53 was likely to be negatively regulated by MDM2 overexpression and epigenetic factors. In conclusion, this study has identified different behaviors in the p53 pathway in 17p13(del) cases. p53 appears to possess haploinssufficiency properties whereby hemizygous p53 loss is sufficient to render a partially defective p53 response. p53 basal level was shown to be the critical determinant of the integrity of the pathway. This has significant clinical implications as this finding can be manipulated to identify patients with different outcome and treatment response. Citation Format: Phaik Ju Teoh, Junli Yan, Wee Joo Chng. Genomic and functional characterization identify different manifestations of p53 pathway in 17p13 deletion cases of multiple myeloma. [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 786. doi:10.1158/1538-7445.AM2013-786
Care of the Woman Who Has Been Raped
Authors: Harriette L. Hampton
Journal: New England Journal of Medicine (1995)

Sexual assault is one of the fastest-growing violent crimes in the United States. In 1990, the Department of Justice reported that the annual incidence of sexual assault was 80 per 100,000 women, accounting for 7 percent of all violent crimes.1 Although the incidence of rape peaks among girls and women 16 to 19 years old in the United States, more than 60,000 rapes of women older than 50 years of age are reported annually.2 In this review I shall discuss the care of postmenarchal women raped by men.Sexual assault is defined as any sexual act performed by one person . . .
S124 The Role of Pancreatic Beta-Cells in the Diurnal Variation of Glucose Handling in Cystic Fibrosis: Abstract S124 Table 1
Authors: D Nazareth, K Mohan, M Walshaw
Journal: Thorax (2012)

<h3>Introduction</h3> An impaired glucose tolerance later in the day may be an early sign of diabetes<sup>1,2</sup>, suggesting that there is diurnal variation in pancreatic endocrine function. This may be important in CF, where glucose handling is deficient even in those without established CF-related diabetes (CFRD). To look at this further, we assessed the response to a glucose challenge throughout the day in CF patients and compared it with healthy controls. <h3>Method</h3> We compared 20 CF patients (17 pancreatic insufficient) without known CFRD with 6 healthy age and BMI matched controls. Following an overnight fast subjects consumed a standardised mixed meal (the gold standard measure of endogenous insulin secretion3, providing an equivalent glucose load to a standard OGTT) at 0800, 1300 and 1800 hours on the same day. Blood glucose and insulin were measured over 120 minutes for each test meal and the area under the curve (AUC) calculated for the entire duration of each test. β-cell indices [β-cell function (%B), insulin sensitivity (%S), insulin resistance (IR)] were measured using the HOMA method4. <h3>Results</h3> See Table (mean±SEM). CF subjects had greater overall glucose levels throughout the day when compared to controls for all 3 tests (p&lt;0.005). β-cell function was highest in the afternoon in the CF group in keeping with a lower AUCglucose at this time and there was a decrease in %S and an increase (p=0.03) in IR with progression of the day. <h3>Conclusions</h3> This study demonstrates insulinopoenia and reduced insulin sensitivity in the CF population resulting in glucose intolerance. Although not the primary defect in CF, there is an increase in insulin resistance as the day progresses. The clinical implications of this study are important not only for the diagnosis of CFRD but also its management in terms of the timing and profiling of exogenous insulin administration. <h3>References</h3> Jarrett, R. BMJ 1(5794): 199–201. Troisi, R. JAMA. 284(24):3157–9. Greenbaum C. Diabetes Care. 31(10):1966–71. Levy J. Diabetes Care 1998; 21: 2191–92.
Abstract 3198: The RNA-binding protein Musashi-1 stabilizes TAC1 mRNA in breast cancer cells.
Authors: George R. Nahas, Raghav G. Murthy, Steven J. Greco, Pranela Rameshwar
Journal: Cancer Research (2013)

Abstract Breast cancer (BC) remains a major public health challenge in the United States. Prognosis for metastatic cancer is poor with nearly all deaths from BC due to metastatic disease. Upon discovery in bone, the five year survival rate of BC patients is approximately eight percent. The tachykinin gene, TAC1, has been implicated in facilitating metastasis of BC to the bone marrow. The predominant product of TAC1 is the neuropeptide, substance P (SP). We have previously demonstrated that in non-malignant cells, TAC1 translation is suppressed by miRNAs. Stimulation with specific cytokines decreased these miRNA to allow synthesis of SP. BC cells (BCCs) lack endogenous expression of the TAC1-specific miRNA, which is consistent with the increased levels of SP in these cells. Herein the present study investigated the translational control of TAC1 mRNA in BCCs. Cytoplasmic extracts from BCCs showed an increase in TAC1 translation and stabilization of its mRNA. These findings led us to bioinformatic analyses of the secondary structure of TAC1 mRNA, which predicted candidate interacting sites in Exons 3 and 7. These predictions were further refined by results from an RNA shift assay that indicated an RNA-binding protein specifically targeting Exon 7. Through western blots and proteomic analysis we identified the RNA-binding protein, Musashi-1 (Msi1), as a putative candidate. Identity was confirmed by RNA supershift assay utilizing an antibody specific for Msi1. Gain-of-function and reporter gene assays utilizing the Msi1 expression vector co-transfected with a luciferase reporter gene linked to the 3′UTR of TAC1, including Exon 7, confirmed a stabilizing role for Msi1 in TAC1 mRNA regulation, concomitant with an increase in substance P. In summary, we identified Msi1 as a novel binding protein for the oncogenic TAC1 mRNA. These findings have implications for the identification of novel targets to treat BC. Citation Format: George R. Nahas, Raghav G. Murthy, Steven J. Greco, Pranela Rameshwar. The RNA-binding protein Musashi-1 stabilizes TAC1 mRNA in breast cancer cells. [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 3198. doi:10.1158/1538-7445.AM2013-3198
Neurologists appeal to health secretary over withdrawal of drug for MS patients
Authors: J. Laurance
Journal: BMJ (2012)

Three neurologists have called on health secretary Jeremy Hunt to intervene after a drug company withdrew off label use of its drug alemtuzumab for patients with multiple sclerosis ahead of trial results into its efficacy.

The doctors said they are disappointed by the actions of Genzyme, a subsidiary of the multinational drug company Sanofi. One called the company “morally corrupt” for disrupting the treatment of patients in favour of future profits.

Genzyme funded two trials of alemtuzumab that were published in the Lancet .1 2 These found that alemtuzumab dramatically cut the relapse rate compared with the current most effective treatment, interferon beta-1a.

Researchers from the University of Cambridge announced that they had found the best treatment yet for multiple sclerosis, which had a “transformative” effect on patients. Alemtuzumab could be suitable for up to two …
BLOOD PRESSURE VARIABILITY AND THE RISK FOR THE DEVELOPMENT OF HYPERTENSION IN NORMOTENSIVE MIDDLE-AGED ADULTS
Authors: Moshe Katz, Assaf Berger, Shaye Kivity, Shlomo Segev, Yechezkel Sidi, Ehud Grossman, Ilan Goldenberg, Elad Maor
Journal: Journal of the American College of Cardiology (2015)
Researchers Gain Insight Into Cell Cycle Delay
Authors: John Bowersox
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Researchers Gain Insight Into Cell Cycle Delay Get access John Bowersox John Bowersox Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 24, 16 December 1992, Pages 1859–1860, https://doi.org/10.1093/jnci/84.24.1859 Published: 16 December 1992