tbuckley/cabot-search huggingface dataset:
F-18 FDG Uptake in Endometrial Cancer
Authors: TADAKI NAKAHARA, HIROFUMI FUJII, MICHIRU IDE, YUKIHITO MOCHIZUKI, WAKOH TAKAHASHI, SEIEI YASUDA, AKIRA SHOHTSU, ATSUSHI KUBO
Journal: Clinical Nuclear Medicine (2001)

Endometrial cancer, which is one of the most common malignant gynecologic diseases, was detected by F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in a 60-year-old woman with abdominal distention. FDG PET revealed heterogeneous and marked accumulation in the endometrium, which was thought to represent endometrial cancer. In addition, focal intense accumulation of FDG in both lungs suggestive of lung metastases were noted. Endometrial cancer and lung metastases were confirmed by endometrial biopsy and computed tomography of the chest, respectively.
Nelson's Syndrome: Frequency, Prognosis, and Effect of Prior Pituitary Irradiation
Authors: THOMAS J. MOORE
Journal: Annals of Internal Medicine (1976)

Previous reports differ regarding the frequency and course of pituitary tumors occurring after adrenalectomy for bilateral adrenal hyperplasia (Nelson's syndrome). In this report, 120 patients who were adrenalectomized for bilateral adrenal hyperplasia were followed for 2 to 20 years. Nine of the 120 developed Nelson's syndrome (8%), the tumors appearing 6 months to 16 years after adrenalectomy. In the majority of cases, the course was benign; seven patients are living an average of 9.7 years after discovery of their tumors. Finally, contrary to previous reports, pituitary irradiation before adrenalectomy did not prevent Nelson's syndrome. Twenty of 120 patients had pituitary irradiation as the initial treatment for bilateral adrenal hyperplasia and two subsequently developed pituitary tumors. Thus, after adrenalectomy for bilateral adrenal hyperplasia, all patients, regardless of previous pituitary irradiation, should be followed indefinitely with periodic X rays of the sella turcica for the possible occurrence of Nelson's syndrome.
Abstract 2291: Downregulation of uPA/uPAR inhibits epithelial to mesenchymal transition (EMT) in intermittent hypoxic DAOY and D283 medulloblastoma cells
Authors: Reshu Gupta, Chandramu Chetty, Praveen Bhoopathi, Sajani S. Lakka, Daniel Fassett, Jeffrey D. Klopfenstein, Dzung H. Dinh, Meena Gujrati, Jasti S. Rao
Journal: Cancer Research (2010)

Abstract Medulloblastoma is the most common, rapidly growing tumor of the cerebellum, which arises in childhood and has a tendency to metastasize via cerebrospinal fluid (CSF) pathways. In addition to surgical resection, post-operative radiotherapy and chemotherapy are the mainstays in treating patients with medulloblastoma. However, these tumors remain among the most challenging pediatric brain tumors. Factors related to the tumor microenvironment are being recognized as fundamental to tumor progression, increased resistance and metastasis. Hypoxia, one of these factors, leads to epigenetic and genetic adaptation of clones and increased EMT, invasiveness and metastasis. Thus, hypoxia is closely associated with tumorigenesis and provides tumors the ability to outgrow the existing vasculature. In this study, we show that intermittent hypoxia has a more pronounced effect than chronic hypoxia and is responsible for EMT, invasion, migration, and survival of hypoxic-conditioned medulloblastoma cells. We also show that Akt and SNAIL are activated under hypoxia, and this response is blocked by plasmid vector-mediated delivery of uPA/uPAR siRNA. The linkage of uPAR to Akt activation under hypoxia provides one mechanism by which uPAR may regulate SNAIL, and thus, promote EMT. The results presented here suggest that, in cells that express high levels of uPAR, induction and maintenance of EMT depends on simultaneous activation of numerous cell-signaling factors downstream of uPAR. This study provides valuable evidence of the anti-tumor efficacy of plasmid vector-mediated delivery of uPA/uPAR siRNA in hypoxic-conditioned medulloblastoma cells to target intermittent hypoxia-induced cell invasion, migration, angiogenesis and EMT and to achieve better therapeutic outcomes in the treatment of malignant medulloblastomas 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 2291.
Portfolio of pap
Authors: Oliver Ellis
Journal: BMJ (2013)

“We lived for three months in a rolled up newspaper in a septic tank. We used to have to get up every morning at six o’clock and clean the newspaper, go to work down the mill, fourteen hours a day, week-in week-out, for sixpence a week, and when we got home our Dad would thrash us to sleep with his belt.”1 ⇑

Every time doctors tell me about their working hours before the European working time directive came into force I think of Monty Python’s Four Yorkshiremen sketch, in which the surrealist troupe try to outdo each other …
Helicobacter pylori and Peptic Ulcer
Authors: Louise Pilote
Journal: Annals of Internal Medicine (1995)

Letters1 March 1995Helicobacter pylori and Peptic UlcerLouise PiloteLouise PiloteCleveland Clinic Foundation, Cleveland, OH 44195. Kuakini Medical Center, Honolulu, HI 96817. Vanderbilt University School of Medicine, Nashville, TN 37232.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-5-199503010-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We commend Nomura and coworkers [1] for using an existing cohort to increase our understanding of the relation between Helicobacter pylori and peptic ulcer disease. However, the nested case–control design that was used has a few methodologic problems. First, the case–control design was used in the context of a cohort design, and principles that apply to the cohort design should be respected. Specifically, the disease status (duodenal or gastric ulcer) at study entry is unknown. Consequently, the population at risk may not have been free of disease when the blood samples were collected. If persons in whom ...REFERENCE1. Nomura A, Stemmermann GN, Chyou PH, Perez-Perez GI, Blaser MJ. Helicobacter pylori infection and the risk for duodenal ulcer and gastric ulceration. Ann Intern Med. 1994; 120:977-81. Google Scholar Author, Article, and Disclosure InformationAuthors: Louise PiloteAffiliations: Cleveland Clinic Foundation, Cleveland, OH 44195. Kuakini Medical Center, Honolulu, HI 96817. Vanderbilt University School of Medicine, Nashville, TN 37232. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1995Volume 122, Issue 5Page: 394-395KeywordsAntibodiesBloodGastric ulcersHelicobacter pyloriPeptic ulcers ePublished: 15 August 2000 Issue Published: 1 March 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Dietetic treatment of phenylketonuria: a follow-up study.
Authors: B. Clayton, A. Moncrieff, G. E. Roberts
Journal: BMJ (1967)

Ordinary school indicates placement with the normal educational system. E.S.N. indicates placement in a school for the educationally subnormal. T.C. indicates placement at a training centre. Hospital indicates placement in a hospital for the subnormal. Rudolph Steiner indicates placement in a special unit. * Consultant Chemical Pathologist, the Hospital for Sick Children, Great Ormond Street, London W.C.I,
NERVOUS AND MENTAL SYMPTOMS IN EXOPHTHALMIC GOITER
Authors: LEWELLYS F. BARKER
Journal: JAMA (1918)

The intimate interrelationship of the endocrine glands and the nervous system is nowhere better illustrated than in the symptomatology of exophthalmic goiter. Though it is now generally agreed that in exophthalmic goiter we have to deal with a thyrointoxication, it is not surprising that the syndrome has been and still is described as a nervous disease, since many of the symptoms recognizable in this disease are admittedly due to disturbances of the neural and psychic functions. Of the four cardinal symptoms of exophthalmic goiter—tachycardia, struma, tremor and protrusion of the eyeballs—no less than three are due to abnormal innervations; and when the host of less striking manifestations of the disease is considered, it is clear that neuropathic and psychopathic phenomena predominate. Even in the disturbances often looked on as non-neural in origin—the changes in the blood, the metabolic disturbances, the disorders of endocrine glands other than the thyroid— there may
P1-01-03: The Cytotoxicity of Select Neutrophils in Cancer Patients and the Role of Chemokines in Inducing Neutrophil Cytotoxicity.
Authors: E Comen, Z Granot, L Norton, R Benezra
Journal: Cancer Research (2011)

Abstract Background: Using murine mammary tumor models, recent research conducted by our laboratory at the Sloan-Kettering Institute indicates that select neutrophils are mobilized by a primary breast tumor and uniquely have the capacity to inhibit metastatic seeding in the lung (Granot Z et al. unpublished). We sought to evaluate the cytotoxic role of select neutrophils in the peripheral blood of breast cancer patients as contrasted with those from women without breast cancer and women with DCIS. In addition, we sought to determine whether the addition of select chemokines to neutrophils from a DCIS patient could induce cytotoxicity. Methods: Neutrophils were purified from the blood of 21 newly diagnosed pre-operative breast cancer patients without evidence of metastatic disease, 9 healthy female volunteers with no history of any cancer, and 3 patients with newly diagnosed DCIS. Cytotoxicity was evaluated by incubating isolated neutrophils with luciferase labeled MDA-MB-231 cells. Luciferase activity, as a reflection of% cell kill, was measured using a Bio-Tek microplate luminescence reader. Neutrophils from a DCIS patient with low cytotoxicity were then co-cultured with various CC chemokines (CCl2, CCL3 and CCL5) or CXCL chemokines (CXCL1, CXCL12, and CXCL16) at 100ng/ml. Results: Significant cytotoxicity was notably observed when MDA-MB-231 cells were co-cultured with neutrophils purified from patients with invasive tumors. Pre-operative breast cancer patients (n=21) had a cell kill range of 0–30% (mean = 12.1%), whereas healthy subjects (n=9) had a cell kill range of 0.2-8% (mean = 2.6%), p&amp;lt;0.004. DCIS patients (N=3) had a cell kill range of 3–4% (mean = 2.7). The addition of select chemokines to neutrophils from a DCIS patient with low cytotoxicity (3.2%) resulted in significant increases in cytotoxicity. Table 1 indicates the relative cytotoxicity percentages from the addition of each chemokine. Conclusions: To date, this preliminary work is the first to demonstrate the cytotoxic role of select neutrophils in the peripheral blood of breast cancer patients as contrasted with those from women without breast cancer. We further demonstrate the novel induction of neutrophil cytotoxicity by select chemokines. Further studies are needed to evaluate the prognostic and therapeutic role of cytotoxic neutrophils as well as the role of chemokines in neutrophil cytotoxicity. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-03.
Human Platelet Collagenase
Authors: Carolyn McI. Chesney, Elvin Harper, Robert W. Colman
Journal: Journal of Clinical Investigation (1974)

The presence of proteolytic enzymes such as cathepsin and elastase in platelets and the important role of collagen in platelet aggregation suggested that collagenase might be present in platelets. Epinephrine, ADP, and collagen liberate collagenase from platelets in plasma as measured by the hydrolysis of [(14)C]glycine-labeled collagen fibrils. The collagenase activity appeared in an early phase of platelet aggregation and was not a part of the release reaction. However, only 50% of the total collagenase could be liberated by the aggregating agents used. Sucrose density gradient analysis of platelet homogenates using appropriate sub-cellular markers indicated that collagenase appeared in both the granule and membrane fractions. Gel-filtered platelets failed to show collagenase activity before exposure to aggregating agents but released more collagenolytic activity than was found in platelet-rich plasma. This observation was explained by the finding that collagenolytic activity was inhibited by normal human plasma. One of the inhibitors is alpha(1)-antitrypsin as demonstrated by decreased inhibition in plasma from a patient with homozygous alpha(1)-antitrypsin deficiency. Platelet collagenase activity could also be demonstrated by its ability to decrease the viscosity of collagen solutions and to produce collagen fragments similar to those produced by other mammalian collagenases on disk gel electrophoresis. The observation that partially purified platelet collagenase could destroy the platelet-aggregating activity of collagen suggests that the enzyme might function in a negative feedback mechanism limiting thrombus formation.
The Opiate Receptors
Authors: E J Simon, J M Hiller
Journal: The Annual Review of Pharmacology and Toxicology (1978)

The extract of the opium poppy is among the oldest materials used for medicinal purposes, and the study of the major alkaloid in this extract, morphine. is one of the oldest areas of biological research. Our lack of understanding on the molecular level of how morphine and its analogues produce their effects may be in large part related to the fact that they exert most of their actions on the central nervous system. the most complex organ in animals and man. The opiates produce a large variety of pharmacological responses, the most important of which are analgesia. euphoria, and addiction. The latter includes the development of tolerance and physiological and psychological dependence. The discovery of opiate receptors in the central nervous system of animals and man and the resulting discovery of endogenous opiate-like ligands for these receptors (discussed in this issue by L. Terenius and introduced briefly in this review) have given rise to considerable activity and excite­ ment in the field of opiate research. In this review we attempt to cover. within the limitations of space, the most significant advances in our knowledge of opiate receptors since their discovery.
Abstract 623: Prostate cancer and B-vitamins
Authors: Adriana Vidal, Delores Grant, Christina Williams, Emma Allott, Elizabeth Masko, Stephen J. Freedland, Cathrine Hoyo
Journal: Cancer Research (2012)

Abstract BACKGROUND. Recent reports suggest that excess of nutrients involved in the one-carbon metabolism pathway increases PC risk, however empirical data are lacking. Our hypothesis was to examine whether excessive intake of one carbon nutrients was associated with PC risk and whether this association was similar in LG vs. HG prostate cancer. METHODS. Veteran American men (272 controls and 144 PC cases) who attended the Durham Veteran American Medical Center, between 2004-2011, were enrolled into a case-control study. Intake of folate, vitamin B12, B6 and methionine were measured using a food frequency questionnaire. Regression models were used to evaluate the association among one-carbon cycle nutrients, MTHFR genetic variants and prostate cancer. RESULTS. Higher methionine intake was positively associated with PC risk, OR=2.1 95%CI 1.1-3.9, p=0.02; a risk which increased for low grade PC or Gleason &amp;lt;7, OR=2.75 (95%CI 1.32-5.73), p=0.007. These associations did not vary by MTHFR C677T genotype, however the cross-product term for the association of MTHFR A1298C variant and methionine was statistically significant, compared to non-carriers (p=0.045). Evidence for associations between B vitamins (folate, B12 and B6) and PC risk were less clear. CONCLUSIONS. Our results suggest that high methionine intake increases PC risk. Higher intakes of folate and vitamin B6 may be protective against advanced prostate cancer- however the associations were weak, while vitamin B12 higher intakes showed a trend for significance for higher PC risk. Individuals carrying MTHFR A1298C variants, and consuming more than the recommended levels of methionine, may be at higher risk for PC. Key words: Prostate cancer (PC), folate, vitamins B6, B12, methionine, methylenetetrahydrofolate reductase (MTHFR). 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 623. doi:1538-7445.AM2012-623
Altered intracellular Ca2+ handling in heart failure
Authors: Masafumi Yano, Yasuhiro Ikeda, Masunori Matsuzaki
Journal: Journal of Clinical Investigation (2005)

Structural and functional alterations in the Ca2+ regulatory proteins present in the sarcoplasmic reticulum have recently been shown to be strongly involved in the pathogenesis of heart failure. Chronic activation of the sympathetic nervous system or of the renin-angiotensin system induces abnormalities in both the function and structure of these proteins. We review here the considerable body of evidence that has accumulated to support the notion that such abnormalities contribute to a defectiveness of contractile performance and hence to the progression of heart failure.
Susceptibility to autoimmune chronic active hepatitis: Human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors
Authors: Peter T. Donaldson, Derek G. Doherty, Karen M. Hayllar, Ian G. McFarlane, Philip J. Johnson, Roger Williams
Journal: Hepatology (1991)

After nearly 18 years of research, the association between human leukocyte antigens A1-B8-DR3 and autoimmune chronic active hepatitis still provokes debate. The principal reasons for this are disease heterogeneity and racial variation in the distribution of human leukocyte antigens between populations. The aim of the present study was to reexamine the relationship between these antigens and autoimmune chronic active hepatitis in a well-characterized series of patients. Ninety-six outpatients with autoimmune chronic active hepatitis and an additional 14 referred for liver transplantation with end-stage autoimmune chronic active hepatitis were studied. Human leukocyte antigen frequencies were compared with those of 100 racially and geographically matched controls. The A1-B8-DR3 haplotype was present in 38% of patients compared with 11% of controls (chi 2 = 20.6, p less than 0.0005). When all the DR3-positive patients were eliminated, there was a striking secondary association with DR4; 35 (80%) of 44 remaining patients were DR4 positive compared with 31 (39%) of 79 DR3-negative controls (Fisher's exact probability test p = 0.000031, pc = 0.0013). In addition patients with A1-B8-DR3 are seen at a significantly younger age than those without (39.75 yr vs. 48.21 yr, p less than 0.025), relapse more frequently (52% of patients with A1-B8-DR3 relapsed on one or more occasions compared with 34% of patients without this haplotype) and are more frequently referred for liver transplantation. These data indicate for the first time that two genes within the major histocompatibility complex closely linked to the DR3 and DR4 genes independently confer susceptibility to autoimmune chronic active hepatitis.
Antibody Response to Polyvalent Pneumococcal Polysaccharide Vaccine in Diabetics
Authors: Thomas R. Beam
Journal: JAMA (1980)

Ten control volunteers and 40 insulin-dependent diabetics were immunized with polyvalent pneumococcal vaccine (Pneumovax). The populations were similar except that diabetics were significantly older. In a double-blind fashion, diabetics were divided into two groups of 20; one received vaccine at baseline and saline placebo four weeks later. The second received saline, then vaccine. Antibody response was measured by radioimmunoassay. In general, insulin-dependent diabetics responded as quickly and equally as controls. Antibody titers did not decline at eight weeks. Incidence and intensity of adverse reactions were similar among diabetics and controls. There was no correlation between antibody response and age (r=-.078), mean glucose concentration (r=-.096), or duration of diabetes (r=-.064). We conclude that insulin-dependent diabetics respond as well as controls to immunization with pneumococcal polysaccharide vaccine.
Role of arachidonic acid metabolism in human platelet activation and irreversible aggregation
Authors: Gundu H. R. Rao, James G. White
Journal: American Journal of Hematology (1985)

Abstract Previous studies from our laboratory have demonstrated that the aggregation response of platelets inhibited by agents blocking cyclooxygenase activity could be restored to a normal state of sensitivity by prior stimulation of α‐adrenergic receptors. Since cyclooxygenase activity and thromboxane synthesis are not absolutely required for irreversible platelet aggregation, it is important to define precisely what role this pathway serves in platelet physiology. The present study has evaluated the influence of agents that selectively block arachidonic acid conversion at different steps of synthesis. Inhibition of peroxidase, cyclooxygenase, lipoxygenase, and thromboxane synthetase blocked the second wave response of platelets to several agonists, but did not cause dissociation of aggregates preformed by prior exposure to arachidonate (AA) or adenosine diphosphate. Phospholipase (A 2 /C) inhibitors, similar to prostaglandin inhibitors, blocked the second wave response of platelets to the action of agonists and, in addition, caused dissociation of aggregates induced by aggregating agents. Results of our study demonstrate that when single agonists are tested at threshold concentrations, products of arachidonate metabolism may play a role in the activation process. However, continued generation of these metabolites does not appear to be essential for the maintenance of irreversible aggregation. When a combination of agents or high concentration of physiological agonists are used, both activation and irreversible aggregation can be secured independent of prostaglandin synthesis or the release reaction.
Application of a Proapoptotic Peptide to Intratumorally Spreading Cancer Therapy
Authors: Renwei Chen, Gary B. Braun, Xiuquan Luo, Kazuki N. Sugahara, Tambet Teesalu, Erkki Ruoslahti
Journal: Cancer Research (2012)

Bit1 is a proapoptotic mitochondrial protein associated with anoikis. Upon cell detachment, Bit1 is released into the cytoplasm and triggers caspase-independent cell death. Bit1 consists of 179 amino acids; for the C-terminal, two thirds of the molecule functions as a peptidyl-tRNA hydrolase, whereas the N-terminus contains a mitochondrial localization signal. Here, we localize the cell death domain (CDD) to the N-terminal 62 amino acids of Bit1 by transfecting cells with truncated Bit1 cDNA constructs. CDD was more potent in killing cells than the full-length Bit1 protein when equivalent amounts of cDNA were transfected. To develop Bit1 CDD into a cancer therapeutic, we engineered a recombinant protein consisting of the CDD fused to iRGD, which is a tumor-specific peptide with unique tumor-penetrating and cell-internalizing properties. iRGD-CDD internalized into cultured tumor cells through a neuropilin-1-activated pathway and triggered cell death. Importantly, iRGD-CDD spread extensively within the tumor when injected intratumorally into orthotopically implanted breast tumors in mice. Repeated treatment with iRGD-CDD strongly inhibited tumor growth, resulting in an average reduction of 77% in tumor volume and eradication of some tumors. The caspase independence of Bit1-induced cell death makes CDD a potentially attractive anticancer agent, because tumor resistance to the main mechanisms of apoptosis is circumvented. Using iRGD to facilitate the spreading of a therapeutic agent throughout the tumor mass may be a useful adjunct to local therapy for tumors that are surgically inoperable or difficult to treat systemically.