tbuckley/cabot-search huggingface dataset:
Tc-99m Stannous Colloid-Labeled Leukocyte Scintigraphy in the Evaluation of the Painful Arthroplasty
Authors: K. K. CHIK, M. A. MAGEE, W. J. BRUCE, R. J. HIGGS, M. G. THOMAS, K. C. ALLMAN, H. VAN DER WALL
Journal: Clinical Nuclear Medicine (1996)

The aim of this study was to evaluate the utility of scintigraphy using leukocytes labeled with Tc-99m stannous colloid in the assessment of painful arthroplasties. The results of three-phase bone scintigraphy and imaging with Tc-99m-labeled leukocytes in 40 patients with painful joint prostheses, requiring the exclusion of infection are reported. Results were compared with microbiologic culture and/or long-term clinical review. Bone scintigraphy had a sensitivity of 100%, a specificity of 64%, and a diagnostic accuracy of 73% in detecting prosthetic infection. Tc-99m-labeled leukocytes yielded a sensitivity of 70%, a specificity of 100%, and a diagnostic accuracy of 93%. Leukocyte scintigraphy improves the specificity of bone scintigraphy in the assessment of the painful prosthetic joint. A positive study is highly suggestive of infection and warrants appropriate treatment.
The (-765 G-&gt;C) promoter variant of the COX-2/PTGS2 gene is associated with a lower risk for end-stage hip and knee osteoarthritis
Authors: E. M. Schneider, W. Du, J. Fiedler, J. Hogel, K. P. Gunther, H. Brenner, R. E. Brenner
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Functional polymorphisms in genes of proinflammatory signalling cascades may contribute to the genetic risk of osteoarthritis (OA). <h3>Objective</h3> To examine a possible association between end-stage OA of the hip and knee joint and a known single nucleotide polymorphism (SNP) of the COX-2 gene promoter. <h3>Methods</h3> The SNP −765 G→C (rs20417) of the COX-2 gene promoter was genotyped by pyrosequencing in 531 (320 women/211 men) patients with OA from the Ulm Osteoarthritis Study and 400 (200 women/200 men) regional controls from the south-west of Germany. <h3>Results</h3> In the whole study population the C allele was associated with a lower risk (per allele OR 0.57; 95% CI 0.43 to 0.75, p&amp;lt;0.0001) and the G allele with a higher risk for end-stage OA. Analysis of subgroups confirmed this result for primary, bilateral, hip and knee OA. <h3>Conclusion</h3> The promoter polymorphism rs20417 of the COX-2 gene contributes to the genetic risk for end-stage hip and knee OA.
Recent developments in the design of angiotensin‐converting enzyme inhibitors
Authors: Matthew J. Wyvratt, Arthur A. Patchett
Journal: Medicinal Research Reviews (1985)

Orally-active angiotensin-converting enzyme inhibitors are rapidly establishing themselves in the therapy of hypertension and congestive heart failure. Concerted efforts in a number of laboratories have now led to the discovery or synthesis of an unparalleled variety of potent inhibitors. The manner in which several of these inhibitors bind to ACE is beginning to be understood. It is hoped that some of the insights to be derived from the SAR and structural studies done with ACE inhibitors will be applicable to other enzyme targets as well. The success of ACE inhibitors as pharmacological tools and in the clinic will also quite certainly encourage future efforts to develop new enzyme inhibitor approaches to drug therapy.
Mirex-induced adaptive liver growth in rats subjected to thyroidectomy
Authors: James D. Yarbrough, Jo M. Grimley, Jaideep V. Thottassery
Journal: Hepatology (1992)

ABSTRPlCT The organochlorine compound mirex (dodecachlorooctahydro–1,3,4–metheno–2H–cyclobuta–CD–pentalene) induces an adaptive liver growth dependent on the hormonal status of the experimental animal. In the intact laboratory rat, mirex induces liver growth that is an expression of both cellular hyperplasia and hypertrophy. However, in rats subjected to adrenalectomy, mirex induces liver growth that is essentially hyperplastic. Corticosterone supplements given to rats subjected to adrenalectomy and treated with mirex restore the hypertrophic component of liver growth. Therefore it appears that the expression of the hypertrophic component of mirex–induced liver growth is corticosterone dependent. To further explore the hormonal modulation of the expression of mirex–induced adaptive liver growth, rats subjected to thyroidectomy were studied. In male rats subjected to thyroidectomy, a single oral dose of mirex (100 mg/kg body wt) increased relative liver weight (liver wt/body wt × 100) by 62% within 72–hr after mirex administration. Liver growth occurred in the absence of [H]thymidine incorporation into liver DNA. Thus the observed liver growth was totally hypertrophic. However, in mirex–dosed rats subjected to thyroidectomy given twice–daily subcutaneous injections of thyroxine (5 mg/kg body wt), relative liver weight was increased by 204% of the control value within 72–hr after mirex administration, and there was a peak of [H]thymidine incorporation into liver DNA 54 hr after mirex administration. These studies suggest that the expression of hyperplasia in mirex–induced adaptive liver growth is thyroxine dependent. (Hepatology 1992;15:923-927).
Effect of Hypnosis on Allergic Skin Responses in Asthma and Hay-fever
Authors: L. Fry, A. A. Mason, R. S. B. Pearson
Journal: BMJ (1964)

Reports of eosinophilic granulomata in the gastro-intestinal tract have been appearing for over 25 years, but until recently the aetiology of these lesions has remained obscure.There is now evidence that at least some cases, especially those occurring in Western Europe, may be caused by the parasite Eustoma rotundatum, which commonly occurs in North Sea herrings, and may be ingested in uncooked or salted herring products, such as " roll-mops."The cases of two patients with an eosinophilic granuloma of the small intestine are reported, one of whom is a fishmonger.A series of 89 cases, with a total of 96 lesions, collected from the literature are reviewed.In about half the cases the lesion was in the stomach or pyloric antrum, and presented with gastric or pyloric symptoms.In a further third the small intestine was involved, causing intestinal obstruction.The granuloma may occur in two forms, diffuse or localized.The histological features are described.Aetiology is discussed, and it is is suggested that eosinophilic granuloma represents a local allergic response to E. rotundatum, due to an immune state acquired by repeated reinfection with the parasite.There is no specific treatment, but the prognosis is good, and conservative management is advocated rather than major resections whenever possible.Steroids have been used on several occasions.
Endoscopic Identification of a Gastric Dieulafoy’s Lesion Following Ephedrine Administration
Authors: E. Brullet, F. Junquera, R. Campo, A. B. Ortega, J. Troy
Journal: Endoscopy (2005)

The diagnosis of Dieulafoy’s lesions may be difficult even for experienced endoscopists [1]. Nearly one-third of patients who have bleeding from Dieulafoy’s lesions require repeated endoscopic examinations before a conclusive diagnosis can be reached [2]. Failure to diagnose this condition is mainly due to the absence of active bleeding or stigmata of recent hemorrhage during endoscopy (bleeding from Dieulafoy’s lesions is often intermittent) [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]. This report describes a case in which on two occasions, the administration of ephedrine to treat propofol-induced hypotension during gastroscopy was followed by the appearance of active bleeding from a gastric Dieulafoy’s lesion that had not been identified on previous endoscopic and angiographic studies. This allowed endoscopic diagnosis of the Dieulafoy’s lesion and successful treatment by elastic band ligation.
Lipid Level Alterations in the Helsinki Heart Study
Authors: Mark R. Goldstein
Journal: JAMA (1989)

<h3>To the Editor. —</h3> The Helsinki Heart Study<sup>1</sup>demonstrated a significant decrease in coronary heart disease morbidity and mortality in middle-aged dyslipidemic men treated with gemfibrozil vs a placebo. Unfortunately, overall mortality was unchanged because of an increase in violence, accidents, and intracranial hemorrhage in the treated group. Further analysis<sup>2</sup>of that study published in the Aug 5 issue of<i>JAMA</i>revealed that the reduction in coronary heart disease incidence over the placebo group was largest in the Fredrickson type IIB and smallest in the type IIA dyslipidemic men, despite the fact that the largest reductions in low-density lipoprotein cholesterol levels were in the type IIA group. Also, changes in lipoprotein levels in the gemfibrozil group were related to medication compliance—subjects were arbitrarily divided into quartiles based on average capsule counts. Data comparing overall mortality in each of the gemfibrozil-treated IIA, IIB, and IV Fredrickson types would be
Low Doses of the Carcinogen Furan Alter Cell Cycle and Apoptosis Gene Expression in Rat Liver Independent of DNA Methylation
Authors: Tao Chen, Angela Mally, Sibel Ozden, J. Kevin Chipman
Journal: Environmental Health Perspectives (2010)

Evidence of potent rodent carcinogenicity via an unclear mechanism suggests that furan in various foods [leading to an intake of up to 3.5 microg/kg body weight (bw)/day] may present a potential risk to human health.We tested the hypothesis that altered expression of genes related to cell cycle control, apoptosis, and DNA damage may contribute to the carcinogenicity of furan in rodents. In addition, we investigated the reversibility of such changes and the potential role of epigenetic mechanisms in response to furan doses that approach the maximum estimated dietary intake in humans.The mRNA expression profiles of genes related to cell cycle, apoptosis, and DNA damage in rat liver treated with furan concentrations of 0.1 and 2 mg/kg bw were measured by quantitative polymerase chain reaction (PCR) arrays. We assessed epigenetic changes by analysis of global and gene-specific DNA methylation [methylation-specific PCR, combined bisulfite restriction analysis (COBRA), and methylated DNA immunoprecipitation chip] and microRNA (miRNA) analyses.The expression profiles of apoptosis-related and cell-cycle-related genes were unchanged after 5 days of treatment, although we observed a statistically significant change in the expression of genes related to cell cycle control and apoptosis, but not DNA damage, after 4 weeks of treatment. These changes were reversed after an off-dose period of 2 weeks. None of the gene expression changes was associated with a change in DNA methylation, although we detected minor changes in the miRNA expression profile (5 miRNA alterations out of 349 measured) that may have contributed to modification of gene expression in some cases.Nongenotoxic changes in gene expression may contribute to the carcinogenicity of furan in rodents. These findings highlight the need for a more comprehensive risk assessment of furan exposure in humans.
Water-Borne Infectious Hepatitis
Authors: James W. Mosley
Journal: New England Journal of Medicine (1959)

SINCE the nineteenth century there have been epidemics of jaundice that have been attributed to water-borne transmission. The evidence accumulated in recent years is sufficiently complete to warrant recognition of this mode of spread of infectious hepatitis as an epidemiologic entity. In this regard, infectious hepatitis is the first viral disease for which a water-borne route of infection has been generally accepted. Such a route has been postulated for poliomyelitis,1 but no studies have been reported in which conclusive evidence was obtained.2 It is believed that person-to-person contact is the most frequent type of transmission of infectious hepatitis, and there . . .
Integrin Signaling Transduces Shear Stress-Dependent Vasodilation of Coronary Arterioles
Authors: Judy M. Muller, William M. Chilian, Michael J. Davis
Journal: Circulation Research (1997)

A direct relationship exists between shear stress and endothelium-dependent NO-mediated vasodilation of blood vessels. The transduction of shear stress to the biochemical signals resulting in the production of NO is, however, unknown. We tested the hypothesis that integrin binding to Arg-Gly-Asp (RGD) peptide sequences in extracellular matrix proteins is a critical step in initiation of the signaling sequence whereby shear stress activates endothelial tyrosine kinase(s) and induces vasodilation of isolated arterioles. Isolated coronary arterioles were exposed to increasing shear stress under control conditions and in the presence of a synthetic peptide, GRGDNP, to competitively inhibit integrin binding to extracellular matrix proteins containing RGD peptide sequences. Intraluminal GRGDNP (0.1, 0.5, and 1.0 mmol/L) inhibited shear stress-induced vasodilation in a concentration-dependent manner. Application of GRGDNP had no effect on endothelium-dependent relaxation to substance P (10 sup -12 to 10 sup -8 mol/L). An inactive structural analogue, GRGESP, did not alter shear stress-induced vasodilation. To further elucidate the integrin involved in shear stress-induced vasodilation, we administered a blocking antibody to the integrin beta 3 chain (F11) and observed significant attenuation of the vasodilation. Shear stress was also associated with an increase in tyrosine kinase activity, as assessed by anti-phosphotyrosine binding. Application of GRGDNP significantly decreased anti-phosphotyrosine binding during shear stress, suggesting a link between tyrosine kinase activation and integrin signaling during this vasodilatory response. Taken together, these results indicate that integrin-matrix interactions, possibly at focal adhesions, are of cardinal importance in the signaling pathway of shear stress-induced vasodilation. (Circ Res. 1997;80:320-326.)
Predicted increased risk of squamous cell carcinoma induction associated with sunbed exposure habits
Authors: P. Tierney, F.R. de Gruijl, S. Ibbotson, H. Moseley
Journal: British Journal of Dermatology (2015)

Solar ultraviolet radiation (UVR) is recognized as the principal environmental cause of skin cancer. In particular, the risk of induction of squamous cell carcinoma (SCC) has been shown to increase with cumulative exposure to UVR. Models of risk of SCC induction have been developed but these do not include the use of sunbeds.To explore the links between sunbed exposure and risk of SCC induction.To this end, the values of published on-site UVR levels emitted from sunbeds were used to provide real measured sunbed exposure levels to inform the model. The model incorporated three conditions of exposure: day-to-day, holiday and sunbed exposure. The risks associated with different exposure scenarios were implemented in the model. Baseline exposure comprised day-to-day and holiday exposure. Relative risk (RR) was defined as the risk of SCC induction from (sunbed + baseline dose)/baseline dose.The RR of SCC induction from estimated median sunbed exposure output [176 standard erythemal dose (SED) per year; 20-35 years of age] in addition to median baseline sun exposure level (166 SED year + 85.5 SED per year holiday) was 1.9 (90% risk increase) up to 55 years of age. A higher sunbed exposure (302 SED per year; 20-35 years of age) produced an RR value of 2.8 (180% increase) at 55 years of age.This is the first time that a risk model for SCC of the skin has been developed that includes estimated sunbed doses derived from measured irradiance data. The model demonstrates that the additional risk associated with sunbed use may be significant, particularly when high-output, fast-tan sunbeds are used.
S1.03 * GLIOBLASTOMA SUBTYPES DEFINED BY QUANTITATIVE IMAGING MAP TO DIFFERENT CANONICAL SIGNALING PATHWAYS
Authors: H. Itakura, A. Achrol, J. Loya, L. Mitchell, T. Azad, S. Echegaray, K. Yeom, S. Napel, G. Harsh, O. Gevaert
Journal: Neuro-Oncology (2014)

We sought to discover subtypes of glioblastoma (GBM) defined by quantitative imaging features and to identify their canonical signaling pathways. Preoperative MR imaging from 121 Stanford patients with de novo, focal, unilateral GBM were analyzed. Two board-certified neuroradiologists and a neurosurgeon reached consensus in delineating Regions-of-Interest (ROIs) around areas of enhancement in each T1 post-contrast MR. We extracted 138 quantitative image features representing signal intensity and morphology of each lesion. We then used Consensus Clustering to define subtypes in the Stanford group. Next, Prediction Analysis for Microarrays (PAM) and the In-Group Proportion (IGP) statistic were used to validate the reproducibility and robustness of our subtype classification in a second cohort of subjects from The Cancer Genome Atlas (TCGA, n = 145). Finally, to map imaging subtypes to particular molecular signaling pathways, we performed Significance Analysis of Microarrays (SAM) on pathway activity estimates derived from analysis of TCGA tumor copy number and RNA sequencing data with the PARADIGM algorithm. Consensus Clustering analysis of the training set identified three clusters whose validity was confirmed in the TCGA cohort (p < 0.0001, p< 0.0001, p = 0.015). Cluster sizes for the TCGA validation cohort (i.e. 45%, 21% and 35%) were similar to those in the Stanford training set (57%, 17% and 26%). Cluster 1 was associated with 49 overexpressed pathways (FDR < 5%) including Wnt, hypoxia, apoptosis, cell proliferation, and angiogenesis signaling pathways while Cluster 2 was characterized by downregulation of these pathways (FDR < 5%). No pathway was significantly associated with Cluster 3. We identified three distinct, robust clusters of focal, unilateral GBM defined by quantitative image signatures. Subtypes identified in a homogeneous Stanford training set were validated in the heterogeneous multi-institutional TCGA data set. Two of our three clusters had significant associations with canonical signaling pathways.
Abstract 348: Extracellular heat shock protein 90 (eHsp90) initiates EMT events and enhances cell motility in prostate cancer
Authors: Michael W. Hance, Udhayakumar Gopal, Jessica Bohonowych, Jennifer S. Isaacs
Journal: Cancer Research (2012)

Abstract Prostate Cancer (PCa) is the most commonly diagnosed malignancy in men, responsible for the second highest lethality. Although early cancer detection and treatment is often curative, subsequent metastatic spread of tumor cells renders the disease incurable. Activation of the epithelial to mesenchymal transition (EMT) genetic program is considered a key event contributing to metastatic potential and subsequent lethality. Although targeting EMT may be a promising approach for improving treatment outcome, the main, potentially druggable, targets driving this pathway in PCa remain poorly defined. Multiple reports indicate that extracellular Hsp90 (eHsp90) promotes cell motility, invasion, and metastasis in a number of cancer cell types. Intriguingly, eHsp90 has been preferentially detected in the serum or plasma from aggressive cancers. Its presence in the serum of metastatic PCa patients implicates a potential causative role in PCa. Therefore, our objective was to investigate whether eHsp90 may influence EMT events, thereby influencing the metastatic potential of PCa. We now report that paired sets of differentially aggressive PCa tumor cell lines exhibited higher expression of eHsp90. Functionally, exposure of PCa cells to eHsp90 elicted a significant increase in cell motility. Inversely, blockade of eHsp90 attenuated the activation of several pro-motility effectors, concomitant with the significant suppression of cell migration. These events were associated with a profound alteration of cellular morphology towards a mesenchymal phenotype. Changes in cell phenotype were coupled with a loss and redistribution of the EMT suppressive gatekeeper protein E-cadherin. eHsp90 was also found to impact on the localization of other junctional proteins known to maintain a cuboidal epithelial phenotype. Finally, eHsp90 was found to transcriptionally upregulate several of the established transcriptional factors known to initiate EMT events. Confirmation of the EMT inducing ability of eHsp90 was determined by focused quantitative real time EMT PCR arrays. Our results therefore highlight a novel role for eHsp90 as a central regulator of EMT events in PCa. Our findings further support the premise that therapeutic targeting of eHsp90 may have the potential to suppress EMT activation and diminish the dissemination and metastatic propensity of PCa tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 348. doi:1538-7445.AM2012-348
Polycythemia Vera Among the Elderly
Authors: Susan S. Devesa
Journal: JAMA (1975)

To the Editor.—  Polycythemia vera has been reported to occur among octogenarians in Modan's review of the literature. 1 Recently, Gunale and Zelkowitz 2 reported a case in a 96-year-old patient. The Third National Cancer Survey 3 has now released its findings concerning polycythemia vera in older individuals.  The Third National Cancer Survey was a project of the National Cancer Institute, which collected data on the incidence of cancer among residents of seven metropolitan areas and two states during the three years 1969 through 1971. This population comprises more than 10% of the population of the United States. Polycythemia rubra vera was included as a reportable neoplasm for this survey since it may represent an early malignancy or a precursor of malignancy.  During the time of the survey, two cases of polycythemia vera among nonagenarians were diagnosed; both individuals were 97 years old. Seventeen cases were diagnosed among persons aged
A Dual Role for Src Homology 2 Domain–Containing Inositol-5-Phosphatase (Ship) in Immunity
Authors: Cheryl D. Helgason, Christian P. Kalberer, Jacqueline E. Damen, Suzanne M. Chappel, Nicolas Pineault, Gerald Krystal, R. Keith Humphries
Journal: The Journal of Experimental Medicine (2000)

In this report, we demonstrate that the Src homology 2 domain–containing inositol-5-phosphatase (SHIP) plays a critical role in regulating both B cell development and responsiveness to antigen stimulation. SHIP−/− mice exhibit a transplantable alteration in B lymphoid development that results in reduced numbers of precursor B (fraction C) and immature B cells in the bone marrow. In vitro, purified SHIP−/− B cells exhibit enhanced proliferation in response to B cell receptor stimulation in both the presence and absence of Fcγ receptor IIB coligation. This enhancement is associated with increased phosphorylation of both mitogen-activated protein kinase and Akt, as well as with increased survival and cell cycling. SHIP−/− mice manifest elevated serum immunoglobulin (Ig) levels and an exaggerated IgG response to the T cell–independent type 2 antigen trinitrophenyl Ficoll. However, only altered B cell development was apparent upon transplantation into nonobese diabetic–severe combined immunodeficient (NOD/SCID) mice. The in vitro hyperresponsiveness, together with the in vivo findings, suggests that SHIP regulates B lymphoid development and antigen responsiveness by both intrinsic and extrinsic mechanisms.