tbuckley/cabot-search huggingface dataset:
A Post-Graduate Lecture on Indigestion: Delivered at the London School of Clinical Medicine
Authors: G. Rankin
Journal: BMJ (1911)

HOSPITALS. -IN selecting "indigestion" as a suitable theme for our ,consideration this afternoon, I have been determined in my choice by the fact that, though often a symptom of many of the organic disorders which we see together at ,the bedside, it is also a frequent-perhaps of all others the most frequent-functional disturbance for the alleviation or cure of which our services are requisitioned.It is no *exaggeration,to say that, whether in hospital or private ,practice, there is no descriptive answer so frequently given to the first inquiry, " What is the matter?" as this com- prehensive word" indigestion."It supplies to the patient a self -satisfying explanation of a wide variety of subjective symptoms, and equally suggests to the physician the greatest of all generalizations for the exercise of his diagnostic and therapeutic acumen.I need scarcely remind you that though functional indigestion is universally regarded as a trivial affection, it may become one of the most serious detriments to the comfort of life.Neglected or imperfectly treated in its earlier stages, when cure is so often possible, it may prove the forerunner, if not the direct etiological antecedent, of such organic diseases of the stomach itself as catarrh, ulceration, or cancer.It may be associated, whether as cause or effect, with many subsequent intestinal disorders, such as constipation, diarrhoea, colitis, appendicitis, or duodenal ulcer.It is constantly responsible for congestion Fof the liver, haemorrhoids, and other consequences of disturbance in the portal circulation.Glycosuria may ensue upon it, and unless recognized and properly treated may gravitate into true diabetes.Albuminuria is no un- common accompaniment, and though functional and intermittent at first may end in true Bright's disease.Phosphaturia, another frequent associate, may pave the way for calculus, cystitis, or pyelitis.The heart often declares its sympathetic association with the digestive disturbance by palpitations, intermittency, or pseudo- -angina; while the arteries probably often owe to the presence in the blood of toxaemic products their first departure from health in the direction of arterio-sclerosis.More almost than any other part of the body the delicate nervous system offers a vicarious sacrifice to digestive unrighteousness in the shape of insomnia, vertigo, migraine, neurasthenia, and a whole army of bewildering neuroses.The respiratory apparatus pays its tribute in cough, dyspnooa, asthma, and bronchial catarrh.The skin enters its protest in the form of prurigo, urticaria, or eczema.There is good reason to believe that some forms of arthritis, certain varieties of anaemia, and many uterine and ovarian disturbances are directly sequential to alcohol, or other form of stimulant.Her tongue is flabby,
Abstract B57: Modeling human metastatic neuroblastoma in immunodeficient mice
Authors: Daniel Bexell, Noémie Braekeveldt, Siv Beckman, Sofie Mohlin, David Gisselsson, Sven Påhlman
Journal: Cancer Research (2014)

Abstract Neuroblastoma is a childhood tumor located in the sympathetic nervous system and most often found in the adrenal gland. Half of the patients have metastases already at diagnosis. There is a need for improved preclinical in vivo models of human high-stage neuroblastoma. Aims: 1) To establish relevant xenograft in vivo models for studying neuroblastoma orthotopic growth and metastatic growth in bone marrow, 2) to detect tumor growth by the two imaging modalities utilized in the clinic, i.e. magnetic resonance imaging (MRI) and I-123-metaiodobenzylguanidine (MIBG)-Single photon emission computed tomography (SPECT), and 3) to characterize orthotopic and bone marrow tumor growth at a pathohistological level. Methods: SK-N-Be2c and KCN-69 neuroblastoma cells were injected into adrenal gland of immunodeficient NSG mice to establish orthotopic tumors. SK-N-Be2c cells were injected directly into femur bone marrow of NSG mice to model bone marrow metastatic growth in a reproducible way. Tumor growth was monitored by MRI or by MIBG-SPECT. Histopathological assessment was performed on formalin-fixed paraffin-embedded tissue sections. Conclusion: We have established a model for orthotopic neuroblastoma growth and characterized the model by MRI and MIBG-SPECT. Orthotopic tumors grow infiltratively into surrounding tissues and resemble the histopathological hallmarks of patient neuroblastoma. We also describe a reproducible in vivo model for neuroblastoma bone marrow metastatic growth. The in vivo models will be important tools for studying mechanisms of neuroblastoma growth and for preclinical drug testing. Citation Format: Daniel Bexell, Noémie Braekeveldt, Siv Beckman, Sofie Mohlin, David Gisselsson, Sven Påhlman. Modeling human metastatic neuroblastoma in immunodeficient mice. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B57.
Soluble factor requirements for the autostimulatory growth of B lymphoblasts immortalized by Epstein-Barr virus.
Authors: J Gordon, S C Ley, M D Melamed, P Aman, N C Hughes-Jones
Journal: The Journal of Experimental Medicine (1984)

B lymphoblasts immortalized by the Epstein-Barr virus (EBV) exhibit autocrine growth stimulation--that is they release a soluble activity to which they respond by growth. A minimally supplemented serum-free medium conditioned by lymphoblastoid cells in their log phase of growth (LCL-CM) was found to contain autostimulatory activity allowing us to explore the mechanism of autocrine growth for these cell-types in defined conditions. Below cell densities capable of supporting autonomous growth, continued proliferation in serum-free medium was dependent on both added LCL-CM and transferrin. Neither activity alone was capable of sustaining growth. At higher cell densities, transferrin by itself was sufficient to maintain the autocrine loop. The action of the autostimulatory factor appeared to reside in its ability to prime cells continually for a proliferative response to transferrin by enhancing the expression of transferrin receptors at the lymphoblast surfaces. The implications of these findings for normal B cell physiology and their possible relation to oncogenesis are discussed.
Abstract LB-69: Targeting CK2 with small molecule CX-4945 modulates NF-kappaB, TP53 and cell survival in head and neck squamous cell carcinoma
Authors: Vishnu Kannabiran, Jay Friedman, Hai Lu, Kenna Anderes, Zhong Chen, Carter Van Waes
Journal: Cancer Research (2010)

Abstract Objective: We previously identified CK2 as an upstream kinase activating NF-kappaB and modulating TP53 mediated signaling pathways. Up regulated CK2 activity is implicated in promoting the malignant phenotype and progression of head and neck squamous cell carcinoma (HNSCC). Here, we investigate the antitumor effects of CX-4945, a selective small molecule inhibitor of CK2. Design: The effects of CX-4945 on cell proliferation were measured by MTT assay in a panel of 9 University of Michigan squamous cell carcinoma (UM-SCC) cell lines. The half maximal inhibitory concentration (IC50) was determined in vitro. CX-4945 inhibition of cell cycle and induction of cell death were measured by DNA flow cytometry. The effects of CX-4945 on the activity of NF-kappaB, BCL-XL, and TP53 promoters were tested by the chemiluminescent reporter gene assay. The anti-tumor activity of orally administered CX-4945 was evaluated in SCID mice bearing UM-SCC-11A xenografts. Results: The IC50 in 9 UM-SCC cell lines ranged from 3.4 µM to 11.7 µM. The UM-SCC-11A cell line used for in vivo studies had an IC50 of 4.07 µM in vitro. CX-4945 showed a concentration and time dependent cell cycle arrest in G1 and G2/M phases accompanied by a significant induction of sub-G0 cells indicating cell death. CK2 inhibition with CX-4945 downregulated the reporter activities of survival-promoting genes such as NF-kappaB and BCL-XL and up regulated the reporter activity of apoptosis-promoting gene TP53 in a concentration and time dependent manner. Furthermore, CX-4945 (75 mg/kg) showed significant tumor growth inhibition (31% (p&amp;lt;0.05)) in UM-SCC-11A xenografts compared to the control group. Conclusions: Inhibition of CK2 via CX-4945 reveals anti-proliferative activity and modulation of NF-kappaB activation in HNSCC cell lines. In vivo studies show significant antitumor activity in a bortezomib-resistant HNSCC xenograft model. CK2 is an unexploited target in HNSCC and CX-4945 demonstrates the potential of a therapeutic agent with this novel mechanism of action for the treatment of head and neck cancers. (Supported by NIDCD intramural project ZIA DC-000016) 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 LB-69.
A case of systemic lupus erythematosus with sideroblastic anaemia terminating in erythroleukaemia.
Authors: H S Ng, H W Ng, R Sinniah, P H Feng
Journal: Annals of the Rheumatic Diseases (1981)

A case of systemic lupus erythematosus is described in which for 10 years the only significant findings were erythema multiforme and vasculitis. Gross hepatosplenomegaly with persistent pancytopenia developed, and bone marrow examination revealed the presence of sideroblasts. The patient9s condition deteriorated, and subsequently she developed a severe bleeding tendency, terminating in erythroleukaemia.
Sonolucent Biliary Cast Preventing Endoscopic Sphincterotomy
Authors: F. Shanahan, J. Lennon, T. Corrigan
Journal: Endoscopy (1981)

Choledocholithiasis forming a total cast of the extra-hepatic biliary tree is described. This is an unusual reason for failure of endoscopic sphincterotomy and could not be diagnosed by ultrasound in this case.
Prevention Conference V
Authors: Sidney C. Smith, Ezra Amsterdam, Gary J. Balady, Robert O. Bonow, Gerald F. Fletcher, Victor Froelicher, Gregory Heath, Marian C. Limacher, Jamshid Maddahi, David Pryor, Rita F. Redberg, Edward Roccella, Thomas Ryan, Lynn Smaha, Nanette K. Wenger
Journal: Circulation (2000)

riting Group II addressed the question of whether tests that assess silent ischemia or inducible ischemia add to prognostic information gained from standard risk factors in asymptomatic patients without known coronary disease.The tests reviewed included the exercise electrocardiogram (ECG), exercise and pharmacological (stress) echocardiogram (echo), exercise and pharmacological myocardial perfusion imaging, ambulatory ECG monitoring, and positron emission tomography.These noninvasive tests detect myocardial ischemia associated with obstructive coronary artery disease (CAD).To date, their greatest application has been diagnostic, in the evaluation of patients with symptoms of angina or a previous clinical manifestation of coronary heart disease (CHD).One limitation of the methods used to detect stress-induced (exercise or pharmacological stress) myocardial ischemia is the dependence of these methods on the presence of flowlimiting coronary stenosis.As with all diagnostic studies, their predictive value is dependent on the prevalence of disease in the population tested.When used in a population with a low prevalence of CHD, such as an asymptomatic population undergoing cardiovascular screening, these tests are expected to have low positive predictive value, and the majority of positive test results represent false-positive responses (Figure).Also central to the discussions of Writing Group II was the recognition that the majority of future events among patients with CHD are related to severity of obstruction, plaque instability, and total atherosclerotic burden. 1 Writing Group II was specifically concerned with delineating the prognostic information available from these tests that could contribute toward identifying patients at higher risk for major CHD-related events.
Studies on Hepatic Bile Obtained from a Patient with an External Biliary Fistula
Authors: Sidney Fink
Journal: New England Journal of Medicine (1956)

RECENTLY, a patient with an external biliary fistula was admitted to the Montefiore Hospital in New York City. Since the opportunity to study hepatic bile extensively over a prolonged period rarely presents itself, it was decided to investigate the general characteristics of the bile, the electrolyte pattern, the lipid pattern and the excretion of certain heavy metals.‡ After the bile electrolyte and cholesterol concentrations had been found to vary within very narrow limits, the possible effect on the bile electrolytes of Diamox, a carbonic anhydrase inhibitor, and on the bile cholesterol of β-sitosterol by mouth was also investigated.Case Report . . .
Immunotherapy for Parasitic Disease
Authors: Franklin A. Neva
Journal: New England Journal of Medicine (1990)

This issue of the Journal includes a report on the benefits of adding interferon gamma to pentavalent antimony in the treatment of refractory or severe visceral leishmaniasis.1 In order to evaluate this new, sophisticated therapy for an old parasitic disease, some background information about visceral leishmaniasis (kala-azar) may be in order. In contrast to cutaneous and mucocutaneous leishmaniasis, in which the protozoan parasite is localized, the visceral disease is caused by growth of the parasite within reticuloendothelial cells throughout the body. It is characterized by fever, weight loss, and hepatosplenomegaly, as well as anemia, leukopenia, and thrombocytopenia. During the active . . .
CHARACTERISTICS OF PATIENTS WITH SCHIZOPHRENIA OR NEUROLOGICAL DISORDER AND VIRUS-LIKE AGENT IN CEREBROSPINAL FLUID
Authors: T.J. Crow, I.N. Ferrier, E.C. Johnstone, J.F. Macmillan, D.G.C. Owens, R.P. Parry, D.A.J. Tyrrell
Journal: The Lancet (1979)
Maternal Use of Hydroxychloroquine Is Associated With a Reduced Risk of Recurrent Anti-SSA/Ro-Antibody–Associated Cardiac Manifestations of Neonatal Lupus
Authors: Peter M. Izmirly, Nathalie Costedoat-Chalumeau, Cecilia N. Pisoni, Munther A. Khamashta, Mimi Y. Kim, Amit Saxena, Deborah Friedman, Carolina Llanos, Jean-Charles Piette, Jill P. Buyon
Journal: Circulation (2012)

Background— A recent case-control study suggested a benefit of hydroxychloroquine (HCQ) in lowering the risk of cardiac manifestations of neonatal lupus (cardiac-NL) in pregnancies of anti-SSA/Ro–positive patients with systemic lupus erythematosus. A historical cohort assembled from 3 international databases was used to evaluate whether HCQ reduces the nearly 10-fold increase in risk of recurrence of cardiac-NL independently of maternal health status. Methods and Results— Two hundred fifty-seven pregnancies of anti-SSA/Ro-positive mothers (40 exposed and 217 unexposed to HCQ) subsequent to the birth of a child with cardiac-NL were identified from 3 databases (United States, England, and France). Exposure was defined as the sustained use of HCQ throughout pregnancy with initiation before 10 weeks of gestation. The recurrence rate of cardiac-NL in fetuses exposed to HCQ was 7.5% (3 of 40) compared with 21.2% (46 of 217) in the unexposed group ( P =0.050). Although there were no deaths in the exposed group, the overall case fatality rate of the cardiac-NL fetuses in the unexposed group was 21.7%. In a multivariable analysis that adjusted for database source, maternal race/ethnicity, and anti-SSB/La status, HCQ use remained significantly associated with a decreased risk of cardiac-NL (odds ratio, 0.23; 95% confidence interval, 0.06–0.92; P =0.037). Similar results were obtained with propensity score analysis, an alternative approach to adjust for possible confounding by indication. Conclusion— Aggregate data from a multinational effort show that in mothers at high risk of having a child with cardiac-NL, the use of HCQ may protect against recurrence of disease in a subsequent pregnancy.
Are the 2005 Dietary Guidelines for Americans Associated With Reduced Risk of Type 2 Diabetes and Cardiometabolic Risk Factors?
Authors: Daisy Zamora, Penny Gordon-Larsen, Ka He, David R. Jacobs, James M. Shikany, Barry M. Popkin
Journal: Diabetes Care (2011)

To examine the prospective association between accordance with the 2005 Dietary Guidelines for Americans (DGA) and subsequent diabetes incidence and changes in cardiometabolic risk factors.
THE RIPENING OPERATION FOR IMMATURE SENILE CATARACT; ITS PLACE.
Authors: FRANK C. TODD
Journal: JAMA (1907)

The earlier belief that a patient must await the time of complete maturity of a cataract before extraction could be performed with safety, led to the development of various artificial methods to hasten ripening. But this meant the performance of a preliminary operation, and Schweigger, in 1890, advocated the removal of immature cataracts after the age of 50, claiming that sufficient hardening of the lens has taken place at this age to enable the operator to remove the entire cortex. Many operators have followed and advocated this practice and the number seems to be constantly on the increase. Yet it is a fact that ripening operations are still practiced by some surgeons with success, in all cases in which conditions make it humane not to wait for nature to bring about maturity, in preference to extracting an unripe cataract, while many other operators often perform the ripening operation under like
Persistent Activation of CD8+ T-cells Characterizes Prediabetic Twins
Authors: Mark Peakman, R David G Leslie, Lorenzo Alviggi, Mohammed Hawa, Diego Vergani
Journal: Diabetes Care (1996)

OBJECTIVE Elevated circulating levels of activated CD3+ T-cells are characteristic of type I diabetes at diagnosis, and activated CD8+ (cytotoxic/suppressor) T-cells predominate in the islet infiltrate. The aim of this study was to examine the peripheral blood of prediabetic and nondiabetic identical twins of patients with type I diabetes for the presence of activated CD8+ T-cells and by comparing these groups, analyze the relationship of such cells to the development of the disease. RESEARCH DESIGN AND METHODS In a 10-year prospective study, blood T-cell subsets (CD3+ total T-cells, CD4+ helper/inducer, and CD8+ cytotoxic/suppressor) were analyzed for evidence of activation (cell surface expression of HLA-DR, CD25) in 18 identical twins of patients with type I diabetes, 8 of whom became diabetic (prediabetic twins), while 10 remained nondiabetic after at least 8 years of follow-up and are now at low risk for type I diabetes. Fifteen healthy individuals were studied as control subjects. RESULTS At the beginning and during the study, percentage levels of activated CD3+ HLA-DR+ T-cells were significantly elevated in prediabetic and low-risk twins compared with control subjects (P &amp;lt; 0.005) but remained high only in prediabetic twins (P &amp;lt; 0.005). Both prediabetic and low-risk twins had elevated levels of HLA-DR+ CD4+ T helper cells compared with control subjects throughout the study (P &amp;lt; 0.001), and these remained high in both (P &amp;lt; 0.001 and P &amp;lt; 0.05, respectively). Only prediabetic twins had elevated levels of HLA-DR+ CD8+ T-cells during the study. These were significantly higher than in control subjects (P &amp;lt; 0.005) and low-risk twins (P &amp;lt; 0.05) and remained persistently elevated to diagnosis (P &amp;lt; 0.001). Abnormally elevated levels of HLA-DR+ CD8+ T-cells in twins indicate a 50% risk of progression to type I diabetes by life-table analysis (P = 0.01), with a positive predictive value of 100%, sensitivity of 50%, and specificity of 100%. Elevated CD25+ T-cell levels in prediabetic and low-risk twins were less marked and less able to discriminate between the twin groups. CONCLUSIONS These results demonstrate that prediabetes is characterized by persistent elevation of HLA-DR+ CD8+ T-cells with the same cytotoxic phenotype as cells predominating in the islet at diagnosis, suggesting that the circulating cells may have a role in the pathogenesis of islet damage.
STUDIES ON TUBERCLE BACILLUS-MONOCYTE RELATIONSHIP
Authors: Jacob Fong, Dennis Chin, Sanford S. Elberg
Journal: The Journal of Experimental Medicine (1961)

Passage of the virulent H37Rv strain of tubercle bacillus in normal or immune systems (normal or immune monocytes suspended in the corresponding serum) resulted in decreased virulence of the bacilli; this was evidenced by the very low mortality rates in mice inoculated intravenously with passaged bacilli. Passaged bacilli when cultivated directly in tween-albumin medium or when grown on glycerol-blood agar plates after recovery from infected mouse tissues proved as virulent as unpassaged bacilli. The decreased virulence of passaged H37Rv was accompanied by loss of ability to bind neutral red. Passaged H37Rv was more sensitive than unpassaged bacilli to inactivation by sodium oleate and by normal monocyte lysate; however, passaged H37Rv was more resistant than unpassaged bacilli to inhibition by streptomycin.
Cutaneous Immunofluorescence in Primary Biliary Cirrhosis
Authors: Henry W. Randle
Journal: JAMA (1981)

Biopsy specimens of normal skin of 11 patients with primary biliary cirrhosis were studied by immunofluorescence for immunoglobulin and complement deposition. Of the 11 patients, seven had positive immunofluorescent staining, primarily in a granular pattern either at the basement membrane zone or around the blood vessels or in both locations. The principal immunoglobulin noted was IgM, which, in six of the seven patients, was seen at the basement membrane zone or around the vessels (or both). Deposition with C3, fibrin, IgA, and IgG was seen less frequently. In this series of patients, cutaneous lesions included discoid lupus erythematosus, lichen planus, vitiligo, chronic bullous lesions of the legs, and scleroderma. Non-organ-specific immunologic markers in this group included elevated levels of IgG, IgM, and IgA, antinuclear antibodies, anti-nDNA, rheumatoid factor, antimitochondrial antibodies, smooth-muscle antibodies, and circulating immune complexes. We wish to add cutaneous immunofluorescence as an additional immunologic marker for primary biliary cirrhosis. (<i>JAMA</i>1981;246:1679-1681)