tbuckley/cabot-search huggingface dataset:
Targeting lactate metabolism for cancer therapeutics
Authors: Joanne R. Doherty, John L. Cleveland
Journal: Journal of Clinical Investigation (2013)

Lactate, once considered a waste product of glycolysis, has emerged as a critical regulator of cancer development, maintenance, and metastasis. Indeed, tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcome. Lactate mediates cancer cell intrinsic effects on metabolism and has additional non-tumor cell autonomous effects that drive tumorigenesis. Tumor cells can metabolize lactate as an energy source and shuttle lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, which induces metabolic reprogramming. Lactate also plays roles in promoting tumor inflammation and in functioning as a signaling molecule that stimulates tumor angiogenesis. Here we review the mechanisms of lactate production and transport and highlight emerging evidence indicating that targeting lactate metabolism is a promising approach for cancer therapeutics.
Assessment of Deoxyuridine Suppression Test in Diagnosis of Vitamin B12 or Folate Deficiency
Authors: S. N. Wickramasinghe, J. E. Longland
Journal: BMJ (1974)

Deoxyuridine (dU) suppression tests have been performed on virtually all marrow samples aspirated at this hospital over the past 12 months. Of the 110 samples studied 26 gave abnormal results, and these 26 samples came from patients deficient in either vitamin B(12) or folate. The dU suppression test was found to be of particular value in the diagnosis of vitamin B(12) or folate deficiency in non-anaemic patients with macrocytosis and equivocal changes in marrow morphology and in patients in whom the serum vitamin B(12) or red cell folate levels were within the normal range.
Cytokine stimulation of nitric oxide formation and differential regulation in hepatocytes and nonparenchymal cells of endotoxemic rats
Authors: Judy A. Spitzer
Journal: Hepatology (1994)

Some disease processes in which increased endotoxin and cytokine levels exist (e.g., sepsis and infantile diarrhea) are also associated with increased levels of blood nitrates, the stable end products of nitric oxide. Available evidence suggests that the effects of an endotoxic environment, with its attendant complex cytokine networks, on liver function are mediated in part by modulation of hepatic nitric oxide synthesis. This hypothesis was tested by means of studying nitric oxide formation and its regulation in liver parenchymal and nonparenchymal cells of rats that had been continuously infused with endotoxin for 30 hr. Hepatocytes of such rats responded to in vitro stimulation for 20 hr by single cytokines, tumor necrosis factor, interleukin-1 beta and interferon-gamma with enhanced nitric oxide formation. In combination, interferon-gamma and endotoxin had greater synergistic effect on hepatocytes than did tumor necrosis factor and endotoxin. Kupffer cells of these endotoxic rats responded to 20 hr of interferon-gamma stimulation with the same enhanced nitric oxide formation we documented previously for endotoxin. Potentiation of the effect, through combination of endotoxin and interferon-gamma, was not as marked as it was with hepatocytes. Challenge of Kupffer cells with tumor necrosis factor or interleukin-1 beta evoked no response. Hepatocytes and Kupffer cells of time-matched, saline solution-treated rats were unresponsive to endotoxin or cytokine stimulation. Small quantities of nitric oxide were produced by endothelial cells spontaneously; this production was somewhat enhanced in cells of the endotoxin-infused rats by a 20-hr in vitro endotoxin challenge. Studies with inhibitors suggest that enhanced nitric oxide formation by endotoxic hepatocytes and Kupffer cells in response to in vitro endotoxin stimulation is differentially regulated. Our findings indicate modulation of nitric oxide generation by cytokines in vitro in various liver cell types of endotoxic rats. A similar scenario may exist in vivo because of the prevailing inflammatory response to endotoxin administration.
Serious paracetamol poisoning and the results of liver transplantation.
Authors: D J Mutimer, R C Ayres, J M Neuberger, M H Davies, J Holguin, J A Buckels, A D Mayer, P McMaster, E Elias
Journal: Gut (1994)

Paracetamol poisoning is the most common cause of fulminant liver failure in the United Kingdom. An accurate assessment of prognosis at the time of referral will allow the appropriate application of liver transplantation in this setting. The outcome of 92 patients consecutively admitted to a specialist liver unit with severe poisoning has been examined. In patients who did not have a transplant, a fatal outcome was seen for 26/82 (32%), and was associated with late presentation, coma grade, prothrombin time prolongation, metabolic acidosis, and renal dysfunction. Cerebral oedema, and sepsis were responsible for most deaths. Prognostic criteria defined at King's College Hospital seemed to predict the outcome of patients who did not have a transplant managed on the Birmingham liver unit. Seventeen patients were listed for transplantation, 10 had liver transplantation, and seven of 10 survived. Seven were listed but not transplanted, and one of seven survived. Psychological rehabilitation of patients who had a transplant has not proved difficult. These results suggest a role for liver transplantation in the management of selected patients with paracetamol poisoning.
P3-211: Number of Surgically Removed Mediastinal Lymph-Nodes (SRMLNs) as prognostic factor for survival in resected early stage non-small-cell lung cancer (NSCLC): a retrospective analysis of a mono-institutional series
Authors: Gabriele Alessandrini, Emilio Bria, Isabella Sperduti, Paolo Visca, Enrico Melis, Virna Cerasoli, Anna Ceribelli, Edmondo Terzoli, Francesco Cognetti, Francesco Facciolo
Journal: Journal of Thoracic Oncology (2007)
Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma
Authors: Christian Jakob, Karl Egerer, Peter Liebisch, Seval Türkmen, Ivana Zavrski, Ulrike Kuckelkorn, Ulrike Heider, Martin Kaiser, Claudia Fleissner, Jan Sterz, Lorenz Kleeberg, Eugen Feist, Gerd-R. Burmester, Peter-M. Kloetzel, Orhan Sezer
Journal: Blood (2006)
Stop trying to integrate organisations
Authors: M. Drage
Journal: BMJ (2015)

If I ruled the NHS I would value and take care of my frontline workforce. I would let them show me how good they were and not forever tell them how bad or inadequate they were. I would not perversely incentivise them, and I would not bully them. I would restore their trust and goodwill in return for a cull of bureaucracy and an end to hyper-regulation, which as with hyper-inflation can lead only to bad things. …
Insulin resistance, serum adiponectin, and proinflammatory markers in young subjects with the metabolic syndrome
Authors: Irina Kowalska, Marek Straczkowski, Agnieszka Nikolajuk, Agnieszka Adamska, Monika Karczewska-Kupczewska, Elzbieta Otziomek, Ida Kinalska, Maria Gorska
Journal: Metabolism (2008)
Fascin Regulates Prostate Cancer Cell Invasion and Is Associated with Metastasis and Biochemical Failure in Prostate Cancer
Authors: Andrew D. Darnel, Emy Behmoaram, Robin T. Vollmer, Jacques Corcos, Krikor Bijian, Kanishka Sircar, Jie Su, Jinsong Jiao, Moulay A. Alaoui-Jamali, Tarek A. Bismar
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Prostate cancer metastasis to secondary organs is considered an initial event in the development of hormone refractory disease and remains the major cause of death among prostate cancer patients. In this study, we investigated the role of fascin, a cytoskeleton actin–bundling protein involved in the formation of filopodia and cell migration, in prostate cancer progression. Experimental Design: Fascin protein expression was examined by immunohistochemistry in a cohort of 196 patients with localized prostate cancer and across several stages of disease progression, including hormone refractory disease. Cellular changes were also assessed in vitro and in vivo in DU145 prostate cancer cell line using fascin gene silencing. Results: Fascin epithelial expression was significantly up-regulated in localized and hormone refractory prostate cancer compared with benign prostate tissue (P &amp;lt; 0.05). Furthermore, high fascin expression was associated with an increased rate of prostate-specific antigen recurrence following radical prostatectomy (P = 0.075), signifying more aggressive clinical course, thus supporting a function for fascin in prostate cancer progression. In cellular models, fascin gene silencing using small interfering RNA in the androgen-independent prostate cancer cell line DU145 decreased cell motility and invasiveness while increasing cell adhesive properties. In addition, fascin small interfering RNA–expressing DU145 cells implanted orthotopically in mouse prostate showed significantly decreased growth (P &amp;lt; 0.005) and drastically prevented the formation of lymph node metastases (P &amp;lt; 0.001) compared with their matched controls. Conclusions: Our data show a function of fascin in the regulation of prostate cancer progression and emphasize the importance of fascin as a prognostic marker for aggressive disease and as a potential therapeutic target for advanced androgen independent disease.
A Study of Factors Related to Efects of Quinidine in Experimental Auricular Flutter
Authors: BARBARA B. BROWN
Journal: Circulation (1952)

Increasing doses of quinidine cause increased slowing of the auricular rate in flutter of circus movement origin, and maximally tolerated doses cause reversion to sinus rhythm. Quinidine lengthens conduction time in the nonfluttering auricle, and the effect increases as the dose is increased. Refractory period is lengthened equally by small and large doses. Experimental results suggest that the effects of quinidine on the auriculoventricular conducting mechanisms are of three types, (1) direct depressant, (2) vagal block, and (3) reflex sympathetic stimulation, and that these effects are manifest to different degrees depending upon dose and the state of innervation to the heart.
Differential upregulation of rat Na-K-Cl cotransporter, rBSC1, mRNA in the thick ascending limb of Henle in different pathological conditions
Authors: Rie Marumo, Sakiko Kaizuma, Shoji Nogae, Masayuki Kanazawa, Tokihisa Kimura, Takao Saito, Sadayoshi Ito, Mitsunobu Matsubara
Journal: Kidney International (1998)
Predicting Survival within the Lung Cancer Histopathological Hierarchy Using a Multi-Scale Genomic Model of Development
Authors: Hongye Liu, Alvin T Kho, Isaac S Kohane, Yao Sun
Journal: PLoS Medicine (2006)

Background The histopathologic heterogeneity of lung cancer remains a significant confounding factor in its diagnosis and prognosis—spurring numerous recent efforts to find a molecular classification of the disease that has clinical relevance. Methods and Findings Molecular profiles of tumors from 186 patients representing four different lung cancer subtypes (and 17 normal lung tissue samples) were compared with a mouse lung development model using principal component analysis in both temporal and genomic domains. An algorithm for the classification of lung cancers using a multi-scale developmental framework was developed. Kaplan–Meier survival analysis was conducted for lung adenocarcinoma patient subgroups identified via their developmental association. We found multi-scale genomic similarities between four human lung cancer subtypes and the developing mouse lung that are prognostically meaningful. Significant association was observed between the localization of human lung cancer cases along the principal mouse lung development trajectory and the corresponding patient survival rate at three distinct levels of classical histopathologic resolution: among different lung cancer subtypes, among patients within the adenocarcinoma subtype, and within the stage I adenocarcinoma subclass. The earlier the genomic association between a human tumor profile and the mouse lung development sequence, the poorer the patient's prognosis. Furthermore, decomposing this principal lung development trajectory identified a gene set that was significantly enriched for pyrimidine metabolism and cell-adhesion functions specific to lung development and oncogenesis. Conclusions From a multi-scale disease modeling perspective, the molecular dynamics of murine lung development provide an effective framework that is not only data driven but also informed by the biology of development for elucidating the mechanisms of human lung cancer biology and its clinical outcome.
Cardiac Imaging in Infants and Children
Authors: Thomas W. Riggs
Journal: JAMA (1983)

The subject of this book is cardiac imaging in infants and children, including chest x-ray films, two-dimensional echocardiography, nuclear medicine, and angiocardiography. It consists of 441 pages with 431 figures, with most figures consisting of two illustrations. The illustrations are well reproduced and clearly labeled. The book is well organized and lucidly written. A clear, logical approach to congenital heart disease is used, and the various imaging modalities are correlated well. This combined approach and synthesis of various imaging modalities is the strength of this book. Although the numerous echocardiograms are of good quality, they do not represent the "state of the art" in ultrasound, since a narrow sector angle and an indistinct near field are depicted. There is also little attention given to the evaluation of postoperative congenital heart disease. This book is definitely a needed addition to the information available on cardiac imaging. It would be particularly useful
Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis
Authors: Maria E. Sarasquete, Ramon García-Sanz, Luis Marín, Miguel Alcoceba, Maria C. Chillón, Ana Balanzategui, Carlos Santamaria, Laura Rosiñol, Javier de la Rubia, Miguel T. Hernandez, Inmaculada Garcia-Navarro, Juan J. Lahuerta, Marcos González, Jesus F. San Miguel
Journal: Blood (2008)
A Randomized Controlled Trial of an HIV Sexual Risk—Reduction Intervention for Young African-American Women
Authors: Ralph J. DiClemente
Journal: JAMA (1995)

<h3>Objective.</h3> —To evaluate the efficacy of a community-based social skills human immunodeficiency virus (HIV) prevention intervention to enhance consistent condom use. <h3>Design.</h3> —A randomized, single-blind controlled trial. <h3>Setting.</h3> —Bayview-Hunter's Point neighborhood of San Francisco, Calif, a predominantly African-American community that is economically disadvantaged. <h3>Participants.</h3> —A sample of 128 sexually active, heterosexual, African-American women 18 through 29 years of age was recruited using street outreach techniques. Participants completed a structured baseline interview; 100 women (78.1%) completed 3-month follow-up interviews. <h3>Intervention.</h3> —Women randomized to the social skills intervention completed five sessions that emphasized ethnic and gender pride, HIV risk—reduction information, sexual self-control, sexual assertiveness and communication skills, proper condom use skills, and developing partner norms supportive of consistent condom use. Women randomized to the HIV education condition participated in a single session that provided HIV risk—reduction information. Women randomized to the delayed HIV education control condition received no HIV risk—reduction information until all follow-up interviews were completed. <h3>Main Outcome Measures.</h3> —Consistent condom use, HIV risk—reduction knowledge, sexual self-control, sexual assertiveness, sexual communication, and partner norms supportive of consistent condom use. <h3>Results.</h3> —Compared with the delayed HIV education control condition, women in the social skills intervention demonstrated increased consistent condom use (adjusted odds ratio [OR], 2.1; 95% confidence interval [CI], 1.03 to 4.15;<i>P</i>=.04), greater sexual self-control (adjusted OR, 1.9; 95% CI, 1.00 to 3.60;<i>P</i>=.05), greater sexual communication (adjusted OR, 4.1; 95% CI, 1.67 to 10.01;<i>P</i>=.002), greater sexual assertiveness (adjusted OR, 1.8; 95% CI, 1.01 to 3.27;<i>P</i>=.05), and increased partners' adoption of norms supporting consistent condom use (adjusted OR, 2.1; 95% CI, 1.08 to 3.87;<i>P</i>=.03). No statistically significant differences in outcome variables were observed between the HIV education condition relative to the delayed HIV education control condition. <h3>Conclusion.</h3> —Community-based HIV risk—reduction programs that are gender relevant and culturally sensitive and provide social skills training can effectively enhance consistent condom use. (<i>JAMA</i>. 1995;274:1271-1276)
Blair will have difficulty in matching European spending
Authors: A. Ferriman
Journal: BMJ (2000)

UK health economists predicted last week that the government would have considerable difficulty in meeting its promise—or aspiration—to increase spending on the NHS to the European average. They agreed, however,that the prime minister's statement was a significant moment for the NHS

Chris Ham, professor of health policy at Birmingham University, said: “It is the boldest statement that any prime minister has ever made on health spending in the 52 year history of the NHS.”

But he and other analysts believe that whether the pledge is fulfilled is highly dependent on the state of the economy over the next five years. Although the coffers at the Treasury are bulging at present—with a surplus estimated at between £10bn ($16bn) and £15bn—the picture five years on …
Cell cycle inhibitors (p27Kip1 and p21CIP1) cause hypertrophy in LLC-PK1 cells
Authors: Yoshio Terada, Seiji Inoshita, Osamu Nakashima, Mimi Tamamori, Hiroshi Ito, Michio Kuwahara, Sei Sasaki, Fumiaki Marumo
Journal: Kidney International (1999)
Chess and Combat: The Algorithm in Medicine
Authors: William H. Crosby
Journal: JAMA (1977)

From their inception with the Cabot cases (now published as clinicopathologic cases from Massachusetts General Hospital in the New England Journal of Medicine ), physicians have learned from clinicopathologic cases (1) how mistaken a clinical diagnosis can be and (2) that the pathologist has the last word. The calm of the morgue is far different from the hurly-burly of the clinic, and clinicians need not feel the same reverence for the pathologists' judgments when confrontation occurs in the clinical laboratory.  This issue ofThe Journal(p 2709) offers an algorithm for the diagnosis of anemia and an example of its application to determine if the laboratory was properly or improperly used. It is a simplistic schema that provides, on the basis of hemoglobin concentration and a computation of average RBC size, a recipe for the workup of anemia. On their procrustean bed, the authors placed charts of 258 consecutive cases of
Arrhythmias Related to Cardioversion
Authors: L. LEMBERG, A. CASTELLANOS, J. SWENSON, A. GOSSELIN
Journal: Circulation (1964)

DC countershock abolished 92 of 101 episodes of atrial fibrillation in 86 patients, an incidence of 91 per cent. Supraventricular arrhythmias were not infrequent immediately after countershock. These were transient and did not complicate the procedure nor were they hazardous to the patient. On two occasions a slow atrioventricular nodal rhythm appeared followed by recurrence of atrial fibrillation a few hours later. Sinus node activity did not return in these patients. Ventricular tachycardia, fibrillation, or standstill did not occur in this series. The following arrhythmias were observed immediately after countershock but prior to the establishment of a regular sinus rhythm: atrioventricular dissociation, 12 times; passive atrioventricular nodal rhythm, five times; atrioventricular nodal tachycardia, five times; atrial flutter or tachycardia, four times. The conversion of fibrillation to flutter by countershock implies that the effect of the electric current was merely to shorten the length of the circulating wave, a phenomenon that can also be observed in the treatment of atrial fibrillation with quinidine. Disorders of rhythm, probably having a different mechanism, were also observed after countershock had established a regular sinus pacemaker. In the group not treated with quinidine prior to countershock (74 episodes) atrial extrasystoles were seen 26 times (35 per cent); atrioventricular nodal extrasystoles or escapes, 18 times (24.3 per cent); atrial flutter or tachycardia, six times (8.1 per cent); atrial fibrillation, eight times (18 per cent); atrioventricular nodal tachycardias, twice (2.6 per cent); and a bizarre, multifocal atrial arrhythmia, once (1.3 per cent). The arrhythmias considered to be responsible for the recurrence of atrial fibrillation and also the possible mechanisms involved were discussed. Pretreatment with quinidine was effective in reducing the incidence of arrhythmias occurring after conversion (27 episodes), atrial extrasystoles six times (22 per cent), atrioventricular nodal extrasystoles or escapes six times (22 per cent); atrial flutter or tachycardia three times (11 per cent); atrial fibrillation once (3.7 per cent); and atrioventricular nodal tachycardia once (3.7 per cent).
Parasites of the Human Heart
Authors: S. E. Gould
Journal: JAMA (1964)

The publication of a volume devoted exclusively to parasites of the human heart attests to the increasing interest in parasitic infections in man. This interest, however, is not merely academic, inasmuch as it is frequently possible to identify the specific agent responsible for the cardiac involvement, and then to institute appropriate treatment. In this valuable brochure, the authors have lucidly and concisely summarized our knowledge of protozoan and metazoan parasites that either invade the heart directly or otherwise influence the heart adversely. The protozoan diseases which are discussed include amebic pericarditis, balantidiasis, kala-azar, Chagas' disease, African trypanosomiasis, malaria, toxoplasmosis, and sarcosporidiosis. The metazoan diseases discussed consist principally of infestations with helminths: (1) the trematodes (flukes), which include schistosomiasis, heterophyiasis, and paragonimiasis; (2) the cestodes ( tapeworms), which cause cysticercosis. echinococcosis, and sparganosis; and ( 3) the nematodes (roundworms), which produce trichinosis, trichuriasis, strongyloidiasis, hookworm disease, ascariasis, and filariasis. As the authors point
The diagnosis of hepatic metastases: Converting a chance into a choice
Authors: Klemens B. Meyer, Jerome P. Kassirer
Journal: Hepatology (1987)

Clinicians frequently perform tests to determine whether patients have liver metastases. Optimal use of a laboratory test requires that the clinician know the test's operating characteristics (its sensitivity and specificity) and have an estimate of the pretest probability that disease is present. We have surveyed studies that examined the value of four biochemical and three imaging tests in establishing a diagnosis of hepatic metastases in patients who underwent an invasive procedure to establish the presence or absence of disease. We have pooled the data from these studies to arrive at values for the sensitivity and specificity of each of these tests, and calculated the predictive values for these tests over a wide range of pretest probabilities of disease. Several examples illustrate how this information may be used clinically. We provide a framework for the optimal interpretation of these commonly ordered tests and indicate the data needed for their complete analysis.