tbuckley/cabot-search huggingface dataset:
Abstract 3368: Down-regulation of LDH-A reduced lactate production and changed the expression of glycolysis-associated transporters
Authors: Henrike Schroer, Christian G. Fabian, Marina Kreutz, Kristina Goetze, Wolfgang Mueller-Klieser
Journal: Cancer Research (2014)

Abstract In the clinic, tumors showing a pronounced Warburg effect (high lactate tumors) are associated with a higher risk of metastasis and a decreased probability of survival of patients. Therefore, manipulations of the glycolytic pathway may alter tumor cell metabolism and might be a way to influence tumors’ aggressiveness, e.g. by down-regulating intracellular lactate levels. To test for this hypothesis B16.SIY E12 murine melanoma cells were stably transfected with shRNA down-regulating LDH-A expression (Lac Low cells). As a control cell line B16.SIY E12 was transfected with a scrambled shRNA construct (Lac High cells). These cell lines were characterized regarding their metabolic properties in vitro, especially lactate production in medium supernatants, the extracellular acidification rates (ECAR) and oxygen consumption rates (OCR). Furthermore, the expression of glycolysis-associated transporters (GLUT1, GLUT3, MCT1, MCT4 and CD147) was determined at the protein level. In a first in vivo set-up ATP, lactate and glucose content of syngeneic experimental tumors were measured using induced metabolic bioluminescence imaging (imBI). Changing LDH-A expression induced differences in lactate production in the two tumor cell lines in vitro with Lac Low cells producing significantly less lactate in 24 h than Lac High cells. Accordingly, Lac Low cells revealed a significantly lower ECAR and a higher OCR than Lac High cells. The protein expression of glycolysis-associated transporters was also influenced by changes in LDH-A expression with Lac High cells showing a significantly higher protein expression of MCT1 and MCT4. The general expression of GLUT1 was unchanged (Western Blot) but membrane localization was higher in Lac High cells (immunofluorescence staining). Measuring metabolite content in experimental tumors of the same cell lines showed that the cells maintained their glycolytic properties with Lac Low tumors showing lower lactate content than Lac High tumors. In summary, down-regulation of LDH-A expression reduced lactate production and membrane localization of glycolysis-associated transporters. The fact, that these characteristic are maintained during the transition from in vitro to in vivo makes this model system useful for systematic studies on therapeutic manipulation of tumor glycolysis and associated pathways. Supported by the Deutsche Forschungsgemeinschaft KFO262, DE 835/2-1 (WMK) + KR1418/8-1 (MK) Citation Format: Henrike Schroer, Christian G. Fabian, Marina Kreutz, Kristina Goetze, Wolfgang Mueller-Klieser. Down-regulation of LDH-A reduced lactate production and changed the expression of glycolysis-associated transporters. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3368. doi:10.1158/1538-7445.AM2014-3368
Early events in the invasion of the human nail plate by Trichophyton mentagrophytes
Authors: A. RASHID, E. SCOTT, M.D. RICHARDSON
Journal: British Journal of Dermatology (1995)

A new in vitro model for the study of nail invasion by dermatophyte fungi was developed. The dermatophyte Trichophyton mentagrophytes, and fragments of finger‐nails and toe‐nails were used. Arthroconidia were inoculated on the ventral surface of the nails. After 6h. adherence and germination of arthroconidia was observed. By 16th, small germ tubes with side branches were evident. At about 24 h. micro‐colonies had become established. At 48 h, a mycelium had formed, and at about 72 h most of the nail fragment was covered with fungal growth. Nail penetration occurred from the ventral surface through the intercellular spaces, and with longer incubation all three layers were invaded by arthroconidia growing through channels. Nail invasion occurred in the absence of added nutrients. Dermatophyte fungi appeared to invade the nail by a combination of mechanical and chemical factors. The model provides a substrate to study the pharmacokinetics and bioavailability of new antifungal agents in situ.
ESCHERICHIA COLI STRAINS THAT CAUSE DIARRHŒA BUT DO NOT PRODUCE HEAT-LABILE OR HEAT-STABLE ENTEROTOXINS AND ARE NON-INVASIVE
Authors: MyronM. Levine, DavidR. Nalin, RichardB. Hornick, ErickJ. Bergquist, DanielH. Waterman, CharlesR. Young, Steven Sotman, Bernard Rowe
Journal: The Lancet (1978)
Growth differentiation factor 15, ST2, high‐sensitivity troponin T, and N‐terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction
Authors: Rajalakshmi Santhanakrishnan, Jenny P.C. Chong, Tze P. Ng, Lieng H. Ling, David Sim, Kui Toh G. Leong, Poh Shuan D. Yeo, Hean Y. Ong, Fazlur Jaufeerally, Raymond Wong, Ping Chai, Adrian F. Low, Arthur Mark Richards, Carolyn S.P. Lam
Journal: European Journal of Heart Failure (2012)
Syndrome of Plasma Cell Dyscrasia, Polyneuropathy, and Endocrine Disturbances
Authors: MICHIO IMAWARI
Journal: Annals of Internal Medicine (1974)

A case of a small amount of IgG λ M component, chronic progressive polyneuropathy, primary hypothyroidism, diabetes mellitus, elevated serum estrogen level, gynecomastia, impotence, generalized lymphadenopathy, peripheral edema, hirsutism, pigmentation and thickening of the skin, slight fever, and excessive perspiration is reported. Five similar cases, all in Japan, are known, and a new syndrome of plasma cell dyscrasia, polyneuropathy, and endocrine disturbances has been suggested recently by other researchers. We think that our case is the sixth case of this syndrome. The pathogenesis of this syndrome is unknown, but some genetic or racial factor may contribute to it.
Reduction of Mortality in Chloramphenicol-Treated Severe Typhoid Fever by High-Dose Dexamethasone
Authors: Stephen L. Hoffman, Narain H. Punjabi, Swiandy Kumala, M. Asril Moechtar, Sri Pandam Pulungsih, Atti Rifajati Rivai, Robert C. Rockhill, Theodore E. Woodward, Agustinus A. Loedin
Journal: New England Journal of Medicine (1984)

We compared high-dose dexamethasone (initial dose, 3 mg per kilogram of body weight) with placebo in a randomized, double-blind trial involving 38 patients with culture-positive, specifically defined severe typhoid fever. The patients in the two treatment groups ranged in age from 5 to 54 and were comparable at the outset. All patients received chloramphenicol. The case-fatality rate of 10 per cent (2 of 20 patients) in the dexamethasone group was significantly lower than the fatality rate of 55.6 per cent (10 of 18) in the placebo group (P = 0.003). There was no significant difference in the incidence of complications among the survivors in either group. Delirium, obtundation, and stupor were grave prognostic signs that were useful for predicting which patients were at high risk of dying before they became comatose or went into shock. Dexamethasone is unnecessary for most patients with typhoid but is recommended for all patients with suspected typhoid fever who are delirious, obtunded, stuporous, comatose, or in shock.
949 A SINGLE- AND MULTIPLE-DOSE ASSESSMENT OF THE SAFETY AND PHARMACOKINETICS OF SCH 900518 AND ITS EFFECT ON THE PHARMACOKINETICS OF MIDAZOLAM IN HEALTHY SUBJECTS
Authors: E. Hughes, M. Treitel, S. Gupta, C. Xu, C. Hu, B. Yue, A. Sheth, M. Corpus, D. Marchisin, P. Prasad, E. O'Mara, A. van Vliet, J. van Lier
Journal: Journal of Hepatology (2009)
Transmission of hepatitis B virus by blood transfusion in Yaounde, Cameroon.
Authors: P M Ndumbe, E Nyouma
Journal: BMJ (1990)

Our results also suggest that treatment with potassium lowers serum cholesterol concentrations, which will be an added advantage.Hence, moderate daily supplements of potassium could be a valuable alter- native to pharmacological methods for controlling mild hypertension, especially in those who are not willing or able to restrict salt intake.Retrospective data suggest that a high intake of potassium may decrease mortality associated with stroke,30 and a long term study to explore the added advantages, if any, of treating hypertension with potassium is worthwhile.
Oral Anticoagulation and Antiplatelets in Atrial Fibrillation Patients After Myocardial Infarction and Coronary Intervention
Authors: Morten Lamberts, Gunnar H. Gislason, Jonas Bjerring Olesen, Søren Lund Kristensen, Anne-Marie Schjerning Olsen, Anders Mikkelsen, Christine Benn Christensen, Gregory Y.H. Lip, Lars Køber, Christian Torp-Pedersen, Morten Lock Hansen
Journal: Journal of the American College of Cardiology (2013)
Intracoronary adenosine deaminase reduces canine myocardial reactive hyperemia.
Authors: D Saito, C R Steinhart, D G Nixon, R A Olsson
Journal: Circulation Research (1981)

We employed intracoronary infusions of calf intestine adenosine deaminase (ADA) to test the hypothesis that adenosine regulates coronary blood flow during myocardial reactive hyperemia (RH). Infusions of 4.5 U ADA/min per kg body weight into the left circumflex coronary artery of 10 open-chest dogs reversibly reduced repayment of flow debt by 30-39% (P less than 0.05) following 5-, 10-, 15-, 20-, and 30-second coronary occlusions, the percentage reduction being independent of occlusion length. ADA reduced peak RH flow rate (17%, P less than 0.05) only after 5-second occlusions. Intracoronary infusions of [131]ADA in seven dogs produced interstitial ADA concentrations between 1.2 and 13.1 U/ml in perfused myocardium and, in five of these dogs, 131I activity in the cardiac node was 1.8-35 times that of contiguous mediastinal tissue. Theophylline, a specific adenosine antagonist, reduced repayment of flow debt by 27-36% (P less than 0.02) in eight dogs, an effect similar to that of ADA. In six other dogs, ADA plus theophylline did not reduce RH flow debt repayment below that produced by ADA alone. This experiment confirms the contribution of adenosine to myocardial RH but shows that this nucleoside accounts for but a third of volume flow. Other, as yet unidentified, factors are collectively more important.
Correlation between mutations in p53 gene and protein expression in human lymphomas
Authors: B. Martinez-Delgado, M. Robledo, E. Arranz, F. Infantes, G. Echezarreta, B. Marcos, C. Sanz, C. Rivas, J. Benitez
Journal: American Journal of Hematology (1997)

A discordance between p53 protein overexpression and the presence of mutations in the gene has been observed in many types of tumors, including human lymphomas. To probe this finding, we have studied a large series of 94 lymphomas of different pathologic types and histologic differentiation. Analyzing exons 5–9, we have found mutations in the p53 gene in 7 of 94 cases distributed in different subtypes: 4/12 (33%) high-grade B-cell non-Hodgkin's lymphomas (B-NHLs), in 1 of 5 (20%) high-grade mucosa-associated lymphomas (MALT), in 1 of 22 (4.5%) anaplastic large cell lymphoma (ALCL), and in 1 of 24 (4%) T-cell NHLs. Immunostaining with anti-p53 antibody DO-7 was possible in 87 lymphomas, and overexpression of p53 protein was observed in 16 cases (18%). A discrepancy between the results of SSCP and immunostaining was detected in 18 tumor samples. Two cases with mutations in the gene showed no altered protein expression and 16 cases overexpressed p53 protein had no point mutations. In these cases, the possibility that mutations occur outside the exons studied has been tested and the entire coding sequence analyzed. Only one case showed a mutation in exon 10, and we found two cases carrying a polymorphism in exon 4 and in intron 10. We conclude that mutations in p53 occur mainly in high-grade B-cell NHLs. Although not limited to a specific subtype of lymphoma, they may be rare in Hodgkin's disease and in low-grade lymphomas. The discrepancies between overexpression and presence of mutations suggest (1) the existence of another mechanism to stabilize the p53 protein, and (2) that the immunohistochemistry cannot be used to predict mutations in the gene. Am. J. Hematol. 55:1-8, 1997. © 1997 Wiley-Liss, Inc.
Smokers Anonymous — Fate of Medical Women — Agony Columns and Dreams
Authors: John Lister
Journal: New England Journal of Medicine (1963)

AFTER last year's report of the Royal College of physicians on the dangers of smoking there was a temporary fall in tobacco sales, but it has been difficult to maintain the impetus of antismoking campaigns. Nevertheless, the Central Council for Health Education is keeping up the pressure and among other efforts has put two vans on the road that are to conduct a mobile antismoking campaign over the next two years. Staffed by university graduates, they are equipped with films, tape recorders, posters and exhibition material. Lecture demonstrations will be given in schools, colleges an. clubs.For those who seek . . .
Emergence of YMDD motif mutant of hepatitis B virus during short-term lamivudine therapy in South Korea
Authors: Yong Han Paik, Hyo Young Chung, Wang-Shick Ryu, Kwan Sik Lee, Ji Sook Lee, Jung Hee Kim, Chun Kyun Lee, Chae Yoon Chon, Young Myoung Moon, Kwang-Hyub Han
Journal: Journal of Hepatology (2001)
Genetic alterations and growth pattern in biliary duct carcinomas: loss of heterozygosity at chromosome 5q bears a close relation with polypoid growth
Authors: E Hidaka, A Yanagisawa, M Seki, T Setoguchi, Y Kato
Journal: Gut (2001)

Biliary duct carcinomas (BDCs) are relatively rare and the carcinogenic mechanisms underlying their induction are poorly understood. There are two growth patterns, polypoid and non-polypoid infiltrative type, but little information is available concerning the relation between growth pattern and genetic alterations. A comparative study was therefore conducted to clarify if differences in genetic changes, including loss of heterozygosity (LOH) at 5q, 9p, 17p, and 18q, and K- ras mutations exist between polypoid and non-polypoid infiltrative type BDCs. LOH analysis was performed using microsatellite markers and K- ras point mutations were analysed by dot blot hybridisation. The incidences of changes for polypoid and non-polypoid infiltrative types were 73% and 26% on 5q, 63% and 59% on 9p, 55% and 50% on 17p, and 20% and 18% on 18q, and 25% and 27% for K- ras mutations. Most importantly, we found the frequency of 5qLOH to be significantly higher with polypoid growth than in the non-polypoid infiltrative type (p&lt;0.05), especially in extrahepatic duct carcinomas (p&lt;0.05). The incidences of other genetic alterations (LOH at 9p, 17p, and 18q, and K- ras mutations) showed similar rates with both tumour types. The present data suggest that 5qLOH may have a close relation with polypoid growth in BDCs.
THE SUICIDAL GESTURE: A STUDY OF 114 MILITARY PATIENTS HOSPITALIZED BECAUSE OF ABORTIVE SUICIDE ATTEMPTS
Authors: MAYER FISCH
Journal: American Journal of Psychiatry (1954)

On the basis of 114 cases treated during one year at a Naval Hospital, various aspects of the problem of abortive suicide attempts have been studied. It was found that the majority are histrionic, aggressive demonstrations, but that this behavior may be encountered in a wide variety of psychotic, neurotic, and personality disorders. Examination of the method employed and of the motives cited by the patients, provided the best clues for evaluation of true suicidal intent. A hypothesis is presented concerning the psychodynamics of insincere suicide gestures, suggesting that this aberration is related to suicide, but that aggression in these cases has not been internalized to the same extent.
Falling research in the NHS
Authors: M. Rees, F. Wells
Journal: BMJ (2010)

A clear national strategy is needed to overcome local barriers to research

The recently published Department of Health leaflet entitled A Junior Doctor’s Guide to the NHS includes a statement that the director general of research and development is responsible for establishing the NHS as an international centre for research excellence.1 Although medical research in the United Kingdom is clearly excellent and world leading, the NHS has underperformed as a leader in clinical research. In 2003 a government sponsored report described how the NHS would be transformed to produce high quality global clinical trials, giving the UK a competitive edge in clinical research.2 Unfortunately, the UK’s participation in global clinical trials dropped from 6% in 2002 to 2% by 2009.3 Other initiatives to support clinical research have also failed to stimulate research by NHS clinicians, including the establishment of the UK Clinical Research Collaboration in 2004, and the inauguration of the NHS research and development strategy under the auspices of the National Institute for Health Research in 2006.4

Despite concern that the introduction of the European Clinical Trials Directive might negatively influence …
Biventricular Pacing Improves the Blunted Force–Frequency Relation Present During Univentricular Pacing in Patients With Heart Failure and Conduction Delay
Authors: Dirk Vollmann, Lars Lüthje, Peter Schott, Gerd Hasenfuss, Christina Unterberg-Buchwald
Journal: Circulation (2006)

Background— In patients with chronic heart failure (CHF) and conduction delay, biventricular (BiV) and left ventricular (LV) pacing similarly improve systolic function at resting heart rates. We hypothesized that BiV and univentricular pacing differentially affect contractile function at increasing heart rates. Methods and Results— Twenty-two patients (aged 66±2 years, QRS 179±8 ms, LV ejection fraction 23±1%) underwent cardiac catheterization before device implantation to measure LV hemodynamics at baseline (rate 68±2 bpm; sinus rhythm n=18; atrial fibrillation n=4) and during BiV, LV, and right ventricular (RV) stimulation at 80, 100, 120, and 140 bpm. BiV and LV pacing at 80 bpm equally augmented dP/dt max as compared with baseline and RV pacing ( P &lt;0.001). Stimulation rate significantly interacted with the effect of BiV, LV, and RV pacing on LV end-diastolic pressure (LVEDP), systolic pressure (LVSP), and dP/dt max . Increasing the rate from 80 to 140 bpm enhanced dP/dt max from 913±28 to 1119±50 mm Hg/s during BiV stimulation ( P &lt;0.001) but had no significant effect on contractility during single-site LV (951±47 versus 1002±54 mm Hg/s) or RV (800±46 versus 881±49 mm Hg/s) pacing. At 140 bpm, LVEDP was lower and LVSP higher during BiV pacing than during RV and LV pacing (LVEDP 12±1 versus 17±1 and 16±1 mm Hg, P &lt;0.001; LVSP 112±5 versus 106±5 and 108±6 mm Hg, P &lt;0.01 and P =0.09; BiV versus RV and LV pacing, respectively). Conclusions— Different modes of ventricular stimulation alter the in vivo force–frequency relation of CHF patients. In contrast to single-site LV and RV pacing, contractile function improves with increasing heart rates during BiV stimulation. This effect may contribute to the enhanced exercise capacity during BiV pacing and could provide a functional benefit over LV-only pacing in patients for whom resynchronization therapy is indicated.
Determinants of drug survival for etanercept in a long‐term daily practice cohort of patients with psoriasis
Authors: J.M.P.A. Reek, P.P.M. Lümig, R.J.B. Driessen, P.C.M. Kerkhof, M.M.B. Seyger, W. Kievit, E.M.G.J. Jong
Journal: British Journal of Dermatology (2013)

Long-term data of etanercept drug survival in patients with psoriasis in daily practice are scarce.The primary objective was to describe drug survival for etanercept in a long-term daily practice cohort of patients with psoriasis. The secondary objective was to identify determinants of drug survival for etanercept in general and separately for discontinuation due to adverse events or ineffectiveness of therapy.Data were extracted from a prospective daily practice cohort of patients treated with biologics for psoriasis. Drug survival was analysed by Kaplan-Meier survival curves and split for two reasons for discontinuation: adverse events and ineffectiveness. Determinants of drug survival were analysed using univariate Cox regression analysis and multivariate Cox regression analysis with backward selection.We included 193 patients (512 patient-years treated) with a maximum treatment duration of 7·5 years. The overall drug survival rates were 77%, 41% and 30% after 1, 4 and 7·5 years, respectively. The mean survival duration was 3·8 years (95% confidence interval 3·4-4·3). Reasons for discontinuation were ineffectiveness (33·7%), adverse events (11·9%), both ineffectiveness and adverse events (4·7%) or other reasons (e.g. pregnancy planned) (5·7%). Determinants related to longer general drug survival were male sex [hazard ratio (HR) 0·55], prior anti-tumour necrosis factor (TNF)-α use (HR 0·57) and lower etanercept dose (HR 0·65). Younger age (HR 0·83), lower body mass index (HR 0·63) and lower etanercept dose (HR 0·71) were related to a decreased risk of discontinuation due to side-effects. A lower mean weekly dose of etanercept (HR 0·63) was related to a decreased risk of discontinuation due to ineffectiveness of therapy.We present the longest analysis of drug survival for etanercept in psoriasis to date. Determinants of longer overall etanercept drug survival were male sex, prior anti-TNF therapy and lower etanercept dose. The determinants of longer drug survival depended on the reason for discontinuation of etanercept.
Canicola Fever in Bristol
Authors: A. M. G. Campbell, J. Macrae, W. G. Manderson, K. C. Sumner, J. C. Broom
Journal: BMJ (1950)

In the U.S.A. the Communicable Disease Centre is the division of the Public Health Service responsible for providing assistance to State health departments in meeting public health emergencies.According to Surgeon-General L. A. Scheele the most extensive investigation
THE RELATION OF BACTERIA TO DISEASE.An Address read before the Illinois State Medical Society at Vandalia, May 19, 1892.
Authors: ELBERT WING
Journal: JAMA (1892)

From the earliest times to our own the mentalbias of physicians has been strongly toward philosophizing. This has been true because of the inherent difficulties of the subject matter with which pathology deals. That it is not due to lack of scientific method in early times, is conclusively shown by the fact that modern theories upon the subject are not in accord. And some theory is just as necessary for a working basis for the doctor of to-day as it was when "The Genuine Works of Hippocrates" contained all the knowledge which a progressive doctor needed to know. And other things being equal, a physician's success and usefulness may be guaged by the completeness of his theories regarding disease, and the thoroughness with which he carries them out in practice. The history of the development of bacteriology gives ample evidence that it has followed the common paths of the progress
Looking after a visiting speaker
Authors: C. Hawkins
Journal: BMJ (1989)

with exogenous cytomegalovirus DNA.The high sensitivity of the polymerase chain reaction makes exclusion of specimen contamination very difficult.89It is thus impossible on the basis of the evidence currently available to say whether the polymerase chain reaction can detect cytomegalo- virus DNA in peripheral blood mononuclear cells collected from people with latent infection.If the polymerase chain reaction is adequately sensitive for this purpose it may prove valuable in studying the nature of latent cytomegalovirus infection and screening patients for this infection.