tbuckley/cabot-search huggingface dataset:
Abstract 4577: Comparative proteomic biomarker screening in laser microdissected tissues from colon adenoma and cancer
Authors: Markus Meyer, Monika Spörl, Agnieszka Harasym, Jörg Spangenberg, Florian Unger, Hartmut Juhl, Kerstin A. David
Journal: Cancer Research (2010)

Abstract Colorectal (CRC) malignancies rank world wide at the third place for tumor diseases and account for an annual mortality rate of 492 000 cases. Although several molecular events are known to be involved in the transition from normal tissue to adenoma and finally to undifferentiated carcinoma it remains a challenge to discover new and more reliable biomarkers for diagnosis, prognosis and prediction of outcome. Towards this end a study was designed to identify potential biomarkers which are associated with the molecular events leading from epithelial adenoma to the early stages of carcinoma. A new biomarker discovery strategy was developed to combine the cell specificity and selectivity of laser capture microdissection (LCM) with the resolution power and sensitivity of liquid-chromatography (LC)-matrix-assisted-laser-desorption/ionization mass spectrometry (LC-MALDI-MS). We carefully selected a group of closely matched patients (n = 10 for each group) afflicted with epithelial adenoma (high dysplasia) or early stages of carcinoma (stage I) and used the derived normal as well as the matched tumor tissue samples to reveal protein expression differences. According to this LC-MALDI-MS strategy microdissected cells (around 10 000 cells) were lysed and extracted proteins were digested with Trypsin. Obtained peptides were separated by capillary reversed phase HPLC (Agilent). The resulting LC-fractions (300) were spotted on prespotted AnchorChip targets (PAC, Bruker) and tryptic fragments subsequently detected by reflector MALDI-MS (ultraflex III, Bruker) measurements. This generated between 5000-7000 ion signals ranging from m/z 800 to 4000. Differential peptide analysis was then performed with the goal to discover robust and significant expression differences between patient groups. Therefore, only m/z ions displaying a minimum twofold difference and a p-value of 0.01 between the tissue samples were considered for further analysis. The selected peptides were subsequently fragmented by MS/MS experiments to reveal their primary sequence and protein identity. Our targeted biomarker discovery approach resulted in the identification of more than 30 biomarker candidates which act in diverse cellular functions and can now be linked to early events (e.g. adenoma vs. normal tissue) or later events (e.g. carcinoma vs. normal) of tumor progression. Currently these biomarkers are validated using antibody based assays to further analyze their potential as markers in a clinical setting. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4577.
Increased osteocyte death in multiple myeloma patients: role in myeloma-induced osteoclast formation
Authors: N Giuliani, M Ferretti, M Bolzoni, P Storti, M Lazzaretti, B Dalla Palma, S Bonomini, E Martella, L Agnelli, A Neri, F Ceccarelli, C Palumbo
Journal: Leukemia (2012)
"IRRADIATION AS A POSSIBLE TREATMENT OF THE DENTAL ROOT 'ABSCESS'"
Authors: Louis H. Levy
Journal: JAMA (1924)

<h3>To the Editor:</h3> —Dr. Bloodgood's letter in the June 7 issue ofThe Journalis of especial interest to me. For one year, from September, 1921, to September, 1922, I conducted a series of experiments on the roentgen-ray treatment of root abscesses. The results were so good that they were gathered together and published under my name in the<i>Dental Cosmos</i>, November, 1922. In that article I described the technic used and the results. The method was tried in about fifty cases. At that time I suggested experimentation along similar lines by other men with the hope that a real cure for dental abscesses might be found. I am glad to see Dr. Bloodgood's letter and welcome his suggestion for other reports on this subject.
Requirements of SLP76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo
Authors: Natalie A. Bezman, Lurong Lian, Charles S. Abrams, Lawrence F. Brass, Mark L. Kahn, Martha S. Jordan, Gary A. Koretzky
Journal: The Journal of Experimental Medicine (2008)

Src homology 2 domain–containing leukocyte phosphoprotein of 76 kD (SLP76), an adaptor that plays a critical role in platelet activation in vitro, contains three N-terminal tyrosine residues that are essential for its function. We demonstrate that mice containing complementary tyrosine to phenylalanine mutations in Y145 (Y145F) and Y112 and Y128 (Y112/128F) differentially regulate integrin and collagen receptor signaling. We show that mutation of Y145 leads to severe impairment of glycoprotein VI (GPVI)–mediated responses while preserving outside-in integrin signaling. Platelets from Y112/128F mice, although having mild defects in GPVI signaling, exhibit defective actin reorganization after GPVI or αIIbβ3 engagement. The in vivo consequences of these signaling defects correlate with the mild protection from thrombosis seen in Y112/128F mice and the near complete protection observed in Y145F mice. Using genetic complementation, we further demonstrate that all three phosphorylatable tyrosines are required within the same SLP76 molecule to support platelet activation by GPVI.
1017-163 Quantitative myocardial contrast echocardiography is useful to evaluate transmural extent of microvascular damage in patients with myocardial infarction
Authors: Yoshimune Hiramoto, Hiroshi Ito, Katsuomi Iwakura, Shigeo Kawano, Atsunori Okamura, Koichi Inoue, Koji Tanaka, Noriyuki Hanibuchi, Kenshi Fujii, Sakurabashi Watanabe
Journal: Journal of the American College of Cardiology (2004)
Idoxuridine in Herpesvirus Encephalitis
Authors: James B. Hanshaw
Journal: New England Journal of Medicine (1970)

Although great strides have been made in the development of virus vaccines against some of the major epidemic diseases of man, disappointingly little has been accomplished in the development of antiviral chemotherapy. There are many serious viral illnesses that are not preventable by universal vaccination and probably will not be in the foreseeable future. Herpesvirus encephalitis, the most common cause of sporadic fatal encephalitis in this country, is such a disease. Of 36 patients with this diagnosis recently described by Olson and his associates, 21 died, and all but three survivors had residual effects.1 The illness is characterized by rapid . . .
The Relationship Between Neurally Mediated Hypotension and the Chronic Fatigue Syndrome
Authors: Issam Bou-Holaigah
Journal: JAMA (1995)

To compare the clinical symptoms and response evoked by upright tilt-table testing in healthy individuals and in a sample of those satisfying strict criteria for chronic fatigue syndrome.Case-comparison study with mean (SD) follow-up of 24 (5) weeks.Tertiary care hospital.A sample of 23 patients with chronic fatigue syndrome (five men and 18 women; mean age, 34 years), each of whom fulfilled the strict diagnostic criteria of the Centers for Disease Control and Prevention, was recruited from regional chronic fatigue support groups and from the investigators' clinical practices. There were 14 healthy controls (four men and 10 women; mean age, 36 years).Each subject completed a symptom questionnaire and underwent a three-stage upright tilt-table test (stage 1, 45 minutes at 70 degrees tilt; stage 2, 15 minutes at 70 degrees tilt with 1 to 2 micrograms/min of isoproterenol; and stage 3, 10 minutes at 70 degrees with 3 to 4 micrograms/min of isoproterenol). Patients were offered therapy with fludrocortisone, beta-adrenergic blocking agents, and disopyramide, alone or in combination, directed at neurally mediated hypotension.Response to upright tilt and scores on symptom questionnaires prior to and during follow-up.An abnormal response to upright tilt was observed in 22 of 23 patients with chronic fatigue syndrome vs four of 14 controls (P < .001). Seventy percent of chronic fatigue syndrome patients, but no controls, had an abnormal response during stage 1 (P < .001). Nine patients reported complete or nearly complete resolution of chronic fatigue syndrome symptoms after therapy directed at neurally mediated hypotension.We conclude that chronic fatigue syndrome is associated with neurally mediated hypotension and that its symptoms may be improved in a subset of patients by therapy directed at this abnormal cardiovascular reflex.
Regulation of the Transcriptional Coactivator FHL2 Licenses Activation of the Androgen Receptor in Castrate-Resistant Prostate Cancer
Authors: Meagan J. McGrath, Lauren C. Binge, Absorn Sriratana, Hong Wang, Paul A. Robinson, David Pook, Clare G. Fedele, Susan Brown, Jennifer M. Dyson, Denny L. Cottle, Belinda S. Cowling, Birunthi Niranjan, Gail P. Risbridger, Christina A. Mitchell
Journal: Cancer Research (2013)

Abstract It is now clear that progression from localized prostate cancer to incurable castrate-resistant prostate cancer (CRPC) is driven by continued androgen receptor (AR), signaling independently of androgen. Thus, there remains a strong rationale to suppress AR activity as the single most important therapeutic goal in CRPC treatment. Although the expression of ligand-independent AR splice variants confers resistance to AR-targeted therapy and progression to lethal castrate-resistant cancer, the molecular regulators of AR activity in CRPC remain unclear, in particular those pathways that potentiate the function of mutant AR in CRPC. Here, we identify FHL2 as a novel coactivator of ligand-independent AR variants that are important in CRPC. We show that the nuclear localization of FHL2 and coactivation of the AR is driven by calpain cleavage of the cytoskeletal protein filamin, a pathway that shows differential activation in prostate epithelial versus prostate cancer cell lines. We further identify a novel FHL2-AR–filamin transcription complex, revealing how deregulation of this axis promotes the constitutive, ligand-independent activation of AR variants, which are present in CRPC. Critically, the calpain-cleaved filamin fragment and FHL2 are present in the nucleus only in CRPC and not benign prostate tissue or localized prostate cancer. Thus, our work provides mechanistic insight into the enhanced AR activation, most notably of the recently identified AR variants, including AR-V7 that drives CRPC progression. Furthermore, our results identify the first disease-specific mechanism for deregulation of FHL2 nuclear localization during cancer progression. These results offer general import beyond prostate cancer, given that nuclear FHL2 is characteristic of other human cancers where oncogenic transcription factors that drive disease are activated like the AR in prostate cancer. Cancer Res; 73(16); 5066–79. ©2013 AACR.
Case 16-1969
Authors: Kurt J. Isselbacher, Austin L. Vickery
Journal: New England Journal of Medicine (1969)

Presentation of Case First admission. A seventy-nine-year-old woman was admitted to the hospital because of diarrhea and vomiting.One year previously she began to experience upper abdominal pain, vomiting and postprandial diarrhea, accompanied by anorexia and weight loss. An upper gastrointestinal series showed a pyloric ulcer, which healed with medical treatment. Ten weeks before admission vomiting and abdominal pain recurred. An attempted upper gastrointestinal series was unsuccessful. An exploratory laparotomy at another hospital disclosed adhesions in the region of the pylorus, and a gastrojejunostomy was performed. Thereafter she remained well until two weeks before entry, when watery diarrhea developed, . . .
Lactose malabsorption in Polynesian and white children in the south west Pacific studied by breath hydrogen technique.
Authors: J M Seakins, R B Elliott, C M Quested, A Matatumua
Journal: BMJ (1987)

Lactose malabsorption was studied by a breath hydrogen technique in 139 Samoan and 68 white schoolchildren. The Samoans were studied in four locations, two in Western Samoa and two in New Zealand, and the white children in both the Cook Islands and New Zealand. The prevalence of malabsorption varied with location: for Samoans it ranged from 41% to 60% in Western Samoa and 0% to 35% in New Zealand; white children had rates of 27% in the Cook Islands and 5% in New Zealand. Environmental factors rather than genetic factors are likely to play the main part in initiating if not perpetuating lactose malabsorption. In both races lactose malabsorption had no effect on the acceptance of, consumption of, and number of gastrointestinal symptoms caused by milk and milk biscuits. Children who had symptoms after consuming a particular dairy product were more likely to say they disliked it than those who reported no symptoms.
FORMULA OF TETRAHYDRONAPHTHALENE ("TETRALIN")
Authors: W. A. Hamor
Journal: JAMA (1923)

To the Editor:  —In the editorial on the Wassermann tuberculosis reaction (The Journal, May 19, p. 1456), tetralin is stated to be  naphthalene with four molecules of water of hydration.  Tetralin, or tetrahydronaphthalene, is produced by the hydrogenation of naphthalene; that is, it is made by the catalytic reduction of naphthalene. It possesses the structural formula:    I hope that this information will make clear that tetralin is not a naphthalene hydrate.
Abstract P4-16-07: Mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT) are closely related to chemotherapy resistance of triple negative breast cancer
Authors: X Deng, J He, HR Chang
Journal: Cancer Research (2013)

Abstract Triple negative breast cancer (TNBC) is among the most aggressive clinical phenotypes and the presence of residual resistant cancer cells of TNBC after chemotherapy is associated with tumor recurrence and metastasis. In recent years more and more evidence highlight a crucial role of CD44 (+)/CD24 (-/low) (stem/progenitor cell-phenotype) population in cancer drug resistance but the mechanism remains elusive. In the current study, we screened for CD44 and CD24 using Fluorescence-activated cell sorting (FACS) in 8 TNBC cell lines before and after Docetaxel and Doxorubicin treatment. Our data showed that after Docetaxel treatment, several CD44 (+)/CD24 (-/low) cell lines changed their phenotypes to CD44 (+)/CD24 (+) and most of the CD44 (+)/CD24 (+) cell lines kept their double positive phenotypes. In contrast, after Doxorubicin treatment, all the CD44 (+)/CD24 (-/low) cell lines kept their phenotypes and all the CD44 (+)/CD24 (+) cell lines changed their phenotypes to CD44 (+)/CD24 (-/low). Furthermore, among the studied 8 cell lines, CD44 (+)/CD24 (+) cell population is always more resistant to Docetaxel and CD44 (+)/CD24 (-/low) population is always more resistant to Doxorubicin. Our finding of EMT transition from CD44 (+)/CD24 (+) to CD44 (+)/CD24 (-/low) in breast cancer cell lines and its inducible by Doxorubicin is consistent with the literature. However, our results showed for the first time that both EMT and the inverse MET in TNBC could be induced by specific chemotherapy drugs based on the phenotypes of CD44 and CD24. Besides, our gene microarray data also showed that TGFb2, BCL2, KLF6 and TAF4 pathways were dramatically changed in both CD44 (+)/CD24 (+) to CD44 (+)/CD24 (-/low) transition and CD44 (+)/CD24 (-/low) to CD44 (+)/CD24 (+) transition. Further study of these pathways in the transitions may give us new clues to overcome the chemotherapy resistance and lead us to develop successful therapeutic strategies of different types of TNBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-16-07.
Points: A silly habit
Authors: P. Carson
Journal: BMJ (1982)

<h3>Objective.</h3> The preclinical period of rheumatoid arthritis (RA) is characterized by the presence of autoantibodies such as anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF). Little is known about the joint symptom profile preceding onset of RA, and whether symptoms are associated with RA autoantibodies. Because first-degree relatives (FDR) of North American Native (NAN) RA probands exhibit multiple risk factors for development of future RA, we investigated the prevalence of joint symptoms in this high-risk population. <h3>Methods.</h3> We studied 306 FDR of NAN patients with RA, 323 NAN controls (NC), and 293 white controls (WC) having no family history of autoimmune diseases. Study subjects completed a questionnaire that asked whether they had pain, swelling, or morning stiffness in their hand joints, or in other joints. Serum samples were gathered at the same time and tested for the presence of ACPA, RF, and high-sensitivity C-reactive protein levels. <h3>Results.</h3> In all cases, FDR were significantly more likely to report experiencing joint symptoms compared to the 2 control groups. FDR also exhibited a significantly higher prevalence of RA autoantibodies than the control groups. There were modest trends for joint symptoms to associate with RA autoantibodies, and individuals who were both ACPA-positive and RF-positive had the highest prevalence of joint symptoms. <h3>Conclusion.</h3> FDR of NAN patients with RA have a higher prevalence of joint symptoms compared to individuals with no family history of autoimmune disease. This finding is only partially explained by a high prevalence of RA autoantibodies in the FDR.
The link between obesity and psoriatic arthritis
Authors: Juan D Cañete, Philip Mease
Journal: Annals of the Rheumatic Diseases (2012)

Psoriatic arthritis (PsA) is classified as a spondyloarthropathy and is characterised by synovitis, enthesitis, dactylitis and spondylitis, usually following the development of cutaneous and nail psoriasis.1 PsA patients have a higher prevalence of some comorbidities (obesity, metabolic syndrome, depression and premature cardiovascular disease) than patients with psoriasis (Pso) without arthritis.2 Increased adiposity and weight gain have been associated with the risk of psoriasis in a prospective study,3 and because 10–30% of Pso patients develop PsA, it is increasingly important to determine whether obesity is solely a comorbid condition in PsA or a risk factor.

A case–control study in patients with Pso found that patient-reported body mass index (BMI) at age 18 years, but not current BMI, was associated with the development of PsA.4 However, the study had some important limitations, including the case definition of PsA, difficulties in establishing a temporal relationship between the factors evaluated, and a lack of validated data on the accuracy of patient recall of BMI at 18 years of age.5

This issue of the journal includes two large prospective studies that suggest obesity is a risk factor for PsA.6 ,7 The cohort study by Love et al , which was conducted using an electronic database of medical records representative of the general UK population and with a 15-year time horizon, found the incidence rates of PsA increased in tandem with BMI, both in the 75 395 people with psoriasis and in the general population (almost 2 million), independent of …
The Treatment of Narcotic Addiction
Authors: M. Loewenthal
Journal: JAMA (1913)

To the Editor:—  As I am interested in the treatment of morphin or opium and alcohol addictions, I read the article by Dr. Alexander Lambert inThe Journal, June 21, 1913, p. 1933, with much interest. Belladonna and scopolamin have been given for years in many drug habit institutions, apparently for the purpose of bringing the patient into a state of delirium to facilitate the abrupt discontinuance of the drug. I think that this kind of treatment should be discarded on account of the bad after-effects of these poisons, especially when administered to psychasthenic patients when their mind is in a weak, deteriorated and morbid condition.  I never undertake the treatment of a case of alcoholic addiction unless the patient can be under my supervision for at least two weeks, and in the case of morphin or opium, from four to six weeks at least is demanded. I have never
US Residency Training Before and After the 1997 Balanced Budget Act
Authors: Edward Salsberg
Journal: JAMA (2008)

Graduate medical education (GME) determines the size and characteristics of the future workforce. The 1997 Balanced Budget Act (BBA) limited Medicare funding for additional trainees in GME. There has been concern that because Medicare is the primary source of GME funding, the BBA would discourage growth in GME.To examine the number of residents in training before and after the BBA, as well as more recent changes in GME by specialty, sex, and type and location of education.Descriptive study using the American Medical Association/Association of American Medical Colleges National GME Census on physicians in Accreditation Council for Graduate Medical Education (ACGME)-accredited programs to examine changes in the number and characteristics of residents before and after the BBA.Differences in the number of physicians in ACGME-accredited training programs overall, by specialty, and by location and type of education.The number of residents and fellows changed little between academic year (AY) 1997 (n = 98,143) and AY 2002 (n = 98,258) but increased to 106,012 in AY 2007, a net increase of 7869 (8.0%) over the decade. The annual number of new entrants into GME increased by 7.6%, primarily because of increasing international medical graduates (IMGs). United States medical school graduates (MDs) comprised 44.0% of the overall growth from 2002 to 2007, followed by IMGs (39.2%) and osteopathic school graduates (18.8%). United States MD growth largely resulted from selection of specialties with longer training periods. From 2002 to 2007, US MDs training in primary care specialties decreased by 2641, while IMGs increased by 3286. However, increasing subspecialization rates led to fewer physicians entering generalist careers.After the 1997 BBA, there appears to have been a temporary halt in the growth of physicians training in ACGME programs; however, the number increased from 2002 to 2007.
Sequential changes in small intestinal structure and function during rotavirus infection in neonatal rats.
Authors: A F Salim, A D Phillips, J A Walker-Smith, M J Farthing
Journal: Gut (1995)

Rotavirus infection is the most common cause of acute diarrhoea in children worldwide. The structural and functional consequences of mammalian rotavirus infection in the small intestine have been incompletely studied and the mechanism of enterocyte damage poorly defined. This study used a neonatal rat model of group B rotavirus infection to study the natural history, clinical features, and the structural and functional consequences of infection in the small intestine. Group B rotavirus infection in eight day old neonatal rats produced diarrhoea by 24-36 hours, which was accompanied by weight loss during the early stages of infection. By seven days the diarrhoea had ceased and body weight was similar to noninfected controls. Rotavirus could be recovered in faeces from 24-72 hours. Light microscopy and morphometry confirmed reduction in villous height in both jejunum and ileum, with a reduction in total mucosal thickness indicating true flat mucosa. Increase in crypt depth followed villous shortening and continued as villous height progressively increased between 96-168 hours. Steady state perfusion of the entire small intestine with a plasma electrolyte solution confirmed the presence of a net secretory state for water between 12-48 hours, with a parallel reduction in sodium absorption. Group B rotavirus infection produces a self limiting acute diarrhoeal illness in neonatal rats similar to human rotavirus infection. Infection causes a reversible flat mucosa resulting from enterocyte loss associated with a net secretory state for water and impaired sodium absorption as a functional correlate. These findings may have relevance for the pathogenesis of human rotavirus infection.