tbuckley/cabot-search huggingface dataset:
Physiology and Clinical Medicine: Bridging the Gap
Authors: D. H. K. Lee, G. P. B. Boissard, H. J. G. Hines
Journal: BMJ (1940)

Many have been the reports, papers, and letters offered to the medical and academic world, countless the hours and great the discussion expended in endeavours to bridge the gap between the medical sciences and clinical medi cine. To intrude upon problems which experienced medical designers have found extremely difficult, and par ticularly to do so at the height of a threat to the structure of civilization itself, must require a substantial excuse. In self-protection we tender a twofold plea for considera tion. First, we do so at the behest of one who has always been in the forefront of educational reform in medicine ; secondly, ours, as a new school, has not only the oppor tunity denied to older institutions, but also the duty of testing out ideas which seem desirable. The time, also, is not as inappropriate as it may at first sight appear. It has been laid down by defence authorities in both Great Britain and the Commonwealth that medical train ing must continue. It is incumbent upon the university authorities, therefore, to see that the training is carried out as expeditiously, thoroughly, and efficiently as possible. No training programme which is built up of unconnected parts or which permits personal antagonism to influence progress can pretend to any of these desiderata.
Coping and Survival in Lung Cancer: A 10-Year Follow-Up
Authors: Hermann Faller, Heinrich Bülzebruck
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Little evidence is available to clarify the influence of psychological variables on the outcome of cancer. The authors studied whether style of coping was predictive of survival in lung cancer. METHOD: A cohort of 103 patients newly diagnosed with cancer was followed for 10 years. Coping was assessed before treatment by using both self-reports and interviewer ratings. RESULTS: In a survival analysis with adjustment for known biomedical prognostic factors such as tumor stage, histological classification, and Karnofsky performance status, a depressive coping style, assessed by patients' self-reports, was linked with shorter survival (relative risk=1.91), and an active coping style, as assessed by interviewers' ratings, was linked with longer survival (relative risk=0.72). CONCLUSIONS: These results support the hypothesis that style of coping predicts survival in lung cancer. The observational design of the study, however, precludes any causal interpretation.
Treatment of high blood pressure: should clinical practice be based on results of clinical trials?
Authors: R G Wilcox, J R Mitchell, J R Hampton
Journal: BMJ (1986)

Revue critique de plusieurs essais therapeutiques publies. Incertitudes liees aux methodologies. Desavantages des traitements anti-hypertenseurs. Frequence de la normalisation de la pression sous placebo. Conseils de prudence
Catheter-Induced Lesions of the Right Side of the Heart
Authors: Barbara S. Ducatman
Journal: JAMA (1985)

We examined prospectively for one year the hearts from 141 consecutive autopsy cases in which a central catheter was present at the time of death. Three deaths were attributable to catheter use, two to perforation. Furthermore, mural thrombi were present in 33 (33%) of 99 patients with pulmonary arterial catheters and in 12 (29%) of 42 patients with central venous catheters. The incidence of pulmonary emboli or bacteremia was no greater in patients with thrombi than in those without. The use of central catheters may thus be complicated by perforation or the development of mural thrombi. Although the thrombi may embolize or may become infected, the incidence and clinical significance appear to be low. The incidence of catheter-related deaths in our autopsy population does not necessarily reflect the incidence in a population of living patients.
Syngamus laryngeus Infection (Syngamosis) with Chronic Cough
Authors: LOUIS WEINSTEIN
Journal: Annals of Internal Medicine (1971)

A 26-year-old woman developed severe paroxysms of coughing after a 10-day vacation in the West Indies. Four and a half months later she expectorated a Y-shaped worm that was identified as the male and the female Syngamus laryngeus in copula; eggs were found in the sputum and tracheal washings. A review of the literature discloses 23 reported cases of syngamosis in man. All appear to be accidental infection by S. laryngeus. The life history of this worm is unknown. Human infection probably occurs via transfer of the adult forms of the parasite from contaminated vegetables to the pharynx.
Risk Factors for the Development of Cholelithiasis in Man
Authors: Lynn J. Bennion, Scott M. Grundy
Journal: New England Journal of Medicine (1978)

UNDERSTANDING of the causes of the cholelithiasis has progressed rapidly since the most likely candidates were first characterized as fair, fat, fertile, 40-year-old women. To summarize this progress, and to indicate how the informed clinician can now anticipate the likely occurrence of gallstones, and perhaps help prevent them, are the aims of this article. We shall emphasize mechanisms thought to underlie the various risk factors that have been identified. The causes of cholesterol-gallstone formation are understood in greater depth and detail than those for pigment-stone formation and will therefore receive greater discussion. Moreover, we shall focus . . .
Abstract 5038: Telomere length linking social contexts and cancer risk in Mexican Americans
Authors: Lixia Han, Hua Zhao, Sara Strom, Carrie R. Daniel, David Chang, Hui Zhang, Yuanqing Ye, Jian Gu, Wong-Ho Chow, Xifeng Wu
Journal: Cancer Research (2014)

Abstract Social contexts have a strong impact on chronic disease risk, including cancer, but how these influences “get under the skin” remains unclear. We hypothesize that telomere length may serve as the molecular link between social contexts and cancer risk. Using quantitative real-time PCR, we measured relative telomere length (TL) on baseline whole blood DNA samples collected from 6,574 participants of the ongoing Mano-a-Mano Mexican American Cohort study. We found that TL decreased linearly with increasing age (P-trend&amp;lt;0.001). In multivariable-adjusted Cox proportional-hazard regression models, longer TL was directly associated with a 2.66-fold increased risk of all-cancer incidence (95% CI= 1.40-5.03). TL was positively associated with several acculturation-related variables. For example, participants with a higher acculturative score with greater stays in the US had a longer TL among participants older than the median age of 38 (P=0.05 and 0.04, respectively). Participants born in the US and with at least a high school education were also more likely to have a longer TL. Among the modifiable risk factors, TL was inversely associated with sedentary or sitting time among women (P=0.01) and among young participants (P=0.01). In other chronic diseases, we found that longer TL was associated with diabetes and gallbladder disease in older participants (P=0.04 and 0.01, respectively). Our results suggest that TL may mediate the relationship between acculturation and related risk factors such as physical inactivity, education, and cancer risk among Mexican Americans. This is our first step in a continuum of research focused on understanding how social and behavioral disparities influence biological pathways in cancer development. Citation Format: Lixia Han, Hua Zhao, Sara Strom, Carrie R. Daniel, David Chang, Hui Zhang, Yuanqing Ye, Jian Gu, Wong-Ho Chow, Xifeng Wu. Telomere length linking social contexts and cancer risk in Mexican Americans. [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 5038. doi:10.1158/1538-7445.AM2014-5038
The half-life of hepatitis B virions
Authors: John M. Murray, Robert H. Purcell, Stefan F. Wieland
Journal: Hepatology (2006)

The virion half-life of hepatitis B virus (HBV) is currently estimated at approximately 1 day. This estimate has been obtained from drug perturbation experiments with reverse transcriptase inhibitors. However, the analyses of those experiments have not considered the export of virions produced from preformed mature DNA-containing HBV capsids in infected cells. Data from 3 acutely infected chimpanzees indicates that there is approximately 10-fold more total intracellular HBV DNA than HBV DNA in blood, and therefore the half-life of virions for chimpanzees during acute infection is 10-fold shorter at 3.8 hours than the half-life associated with export of total intracellular HBV DNA. Mathematical model simulations duplicating the viral dynamics observed in drug perturbation experiments suggest a half-life of at most 4.4 hours for HBV virions in chronically infected humans, significantly shorter than current estimates, but consistent with the half-lives of virions for hepatitis C virus and HIV. This faster turnover of HBV in blood indicates a correspondingly higher replication rate and risk of mutation against hepatitis B antiviral therapy. In conclusion , we find the half-life of HBV virions is approximately 4 hours, significantly shorter than current estimates of 1 day. This new value is consistent with virion half-life estimates for HIV and hepatitis C virus.
Reciprocal Regulation of SOCS 1 and SOCS3 Enhances Resistance to Ionizing Radiation in Glioblastoma Multiforme
Authors: Hong Zhou, Rika Miki, Mervi Eeva, Francesca M. Fike, David Seligson, Lu Yang, Akihiko Yoshimura, Michael A. Teitell, Christina A.M. Jamieson, Nicholas A. Cacalano
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The expression of suppressors of cytokine signaling 1 (SOCS1) and SOCS3 genes is dysregulated in several solid tumors, causing aberrant activation of cell growth and survival signaling pathways. In this study, we analyzed SOCS1 and SOCS3 gene expression in glioblastoma multiforme (GBM) and studied the role of each protein in GBM cell signaling and radiation resistance. Experimental Design: SOCS1 and SOCS3 gene expression was analyzed in 10 GBM cell lines by reverse transcription-PCR and Western blotting. SOCS3 expression was also studied in 12 primary GBM tissues by immunohistochemistry. The methylation status of the SOCS1 and SOCS3 loci was determined by methylation-specific PCR. Extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) activation in GBM cell lines overexpressing SOCS1 or lacking SOCS3 was determined by phosphorylated-specific Western blotting. Radiation responses in SOCS1-positive and SOCS3-deficient GBM cell lines and fibroblasts from wild-type and SOCS1 or SOCS3 knockout mice were studied in a clonogenic survival assay. Results: All GBM cell lines tested lacked SOCS1 expression, whereas GBM cell lines and primary GBM tumor samples constitutively expressed SOCS3. SOCS1 gene repression was linked to hypermethylation of the SOCS1 genetic locus in GBM cells. Reintroduction of SOCS1 or blocking SOCS3 expression sensitized cells to radiation and decreased the levels of activated ERK MAPKs in GBM cells. Conclusions: SOCS1 and SOCS3 are aberrantly expressed in GBM cell lines and primary tissues. Altered SOCS gene expression leads to increased cell signaling through the ERK-MAPK pathway and may play a role in disease pathogenesis by enhancing GBM radioresistance.
Steroids should never be given until possible herpes zoster infection has been excluded
Authors: J C Devine
Journal: BMJ (1997)

Editor—I believe that a recent brief report of a case by S Ali Raza and C P Fielder in Minerva contained inaccuracies; in addition it failed to mention the most important practical clinical implication of the condition that is described.1 The authors report that a 66 year …
The Nuclear Matrix Protein, NRP/B, Enhances Nrf2-Mediated Oxidative Stress Responses in Breast Cancer Cells
Authors: Seyha Seng, Hava Karsenty Avraham, Shuxian Jiang, Suping Yang, Masayuki Sekine, Noam Kimelman, Huchun Li, Shalom Avraham
Journal: Cancer Research (2007)

Abstract The transcription factor NF-E2–related factor 2 (Nrf2) translocates into the nucleus and activates phase II genes encoding detoxification enzymes and antioxidant proteins, resulting in the protection of cells from oxidative insults. However, the involvement of Nrf2-mediated oxidative stress responses in breast cancer cells is largely unknown. Notably, during our study of the Nrf2 pathway in breast cancer cells, we observed that the nuclear matrix protein NRP/B was expressed and colocalized with Nrf2 in these cells, suggesting that NRP/B is involved in Nrf2-mediated oxidative stress responses. The expression level of NRP/B was variable in different breast cancer cells and breast cancer tissues, and was found to be localized in the nucleus. NRP/B expression was increased after exposure to the oxidative stress agent, hydrogen peroxide (H2O2), particularly in the highly aggressive MDA-MB-231 breast cancer cells. Association of NRP/B with Nrf2 in vitro and in vivo was observed in MDA-MB-231 breast cancer cells, and this association was up-regulated upon exposure to H2O2, but not to sodium nitroprusside, SIN-1, and DETA-NO. NRP/B also enhanced Nrf2-mediated NAD(P)H:quinine oxidoreductase 1 promoter activity. Thus, this study reveals that NRP/B enhances oxidative stress responses in breast cancer cells via the Nrf2 pathway, identifying a novel role of nuclear matrix protein(s) in oxidative stress responses. [Cancer Res 2007;67(18):8596–604]
1073-141 Transthoracic echocardiographic assessment of thickness of intima-media complex and calcified lesions of the left anterior descending coronary artery
Authors: Masami Nishino, Takahito Tamai, Tamaki Itakura, Shinichiro Suna, Yasuyuki Egami, Isao Kondo, Ryu Shutta, Kenjiro Tanaka, Takayoshi Adachi, Hideo Tanahashi, Jun Tanouchi, Yoshio Yamada, Takenobu Kamada
Journal: Journal of the American College of Cardiology (2004)
Hypochondriasis Influences Quality-of-Life Outcomes in Patients with Chronic Fatigue
Authors: Peter Manu, Glenn Affleck, Howard Tennen, Priscilla A. Morse, Javier I. Escobar
Journal: Psychotherapy and Psychosomatics (1996)

Background: To determine how hypochondriacal symptoms influence the quality-of-life outcomes of patients with a chief complaint of chronic fatigue. Methods: Cross-sectional cohort study of a consecutive sample of 71 patients (mean duration of fatigue of 4.1 years). Forty-eight (68%) patients met criteria for current major depression and 32 (45%) met criteria for chronic fatigue syndrome (CFS). All patients received a comprehensive medical and psychiatric evaluation. Quality-of-life and physical, depressive and hypochondriacal symptom scores were assessed through reliable self-report questionnaires and a structured interview. A path model expressing the relation between predictor variables (hypochondriasis and depression), intervening variables (physical symptoms) and quality of life was postulated and evaluated using structural equation methods. Results: The paths linking hypochondriasis with physical symptoms and mental health and the path connecting physical symptoms and quality of life were each statistically significant. The model applied especially well to patients who fulfilled CFS criteria. Conclusions: The quality of life of chronic fatigue patients correlates with the severity of their physical symptoms and their hypochondriacal disposition toward illness.
Fibrocongestive splenomegaly in sickle cell disease: A distinct clinicopathological entity in the Eastern province of Saudi Arabia
Authors: Rajan Chopra, Abdul Rahman Al‐Mulhim, Ahmed Taher Al‐Baharani
Journal: American Journal of Hematology (2005)

Sickle cell disease displays a unique progression in the Eastern province of Saudi Arabia, where splenomegaly with hypersplenism is noted with high frequency in the adolescent and adult patients. The late persistence of splenomegaly although likely reflects the milder progression of sickle cell disease in this region; nevertheless, it predisposes the patients to increased morbidity. The present study documents the characteristic clinicopathological features of splenomegaly associated with sickle cell disease in the Al-Hassa region of Eastern province Saudi Arabia. Forty-four cases of sickle cell disease patients in whom splenectomy was performed during 1999-2003 were studied. The hemoglobinopathy profiles of the patients (age range 5-42 years) comprised sickle cell anemia (8 cases), sickle cell anemia with high fetal hemoglobin (23 cases), and sickle cell-beta degrees thalassemia (13 cases). All patients had manifestations of hypersplenism and 39 patients experienced episodes of minor-type sequestration crisis. Splenectomy was effective in ameliorating the hematological abnormalities in all cases, without any major complications in the follow-up period. The splenectomy specimens showed moderate-to-marked enlargement in most cases, with histological features of fibrocongestive splenomegaly and prominent Gandy-gamma body formations. Micro-infarcts in 27 cases and gross infarctions in 9 cases were evident. The relationship of persistent splenomegaly with higher fetal hemoglobin levels and splenic hypofunction is examined along with the significance of splenectomy in these cases.
Heparan sulfate side chains are essential for the modulation of IL-1 signaLs by syndecan-4 in RA synovial fibroblasts
Authors: Lars Godmann, Athanasios Stratis, Christoph Cromme, Frank Echtermeyer, Thomas Pap, Jessica Bertrand
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> Activated synovial fibroblasts (SFs) are key players during RA disease progression. They exhibit a tumour-like invasive behavior, which is most likely induced by a continuous stimulation with ECM molecules, growth-factors and inflammatory cytokines, like IL-1. Syndecan-4 (sdc4), a transmembrane heparan sulfate proteoglycan, has been implicated recently in the modulation of cytokine signaling and has been found to be upregulated in RA-SF. Specifically, sdc4 is been shown to be involved in Erk signalling upon IL-1 stimulation in chondrocytes. However, the role of scd4 side chains and the underlying mechanisms of sdc4 signaling are largely unknown. <h3>Materials and methods</h3> In order investigate the influence of heperan sulfate side chains on sdc4 signaling, different sdc4 side chain mutants were designed using overlap PCR. The authors mutated the serine residues, which constitute the heparan sulphate attachment sites to alanines, thereby preventing side chain asssembly. Laser scanning fluorescence microscopy of transiently transfected Cos-7 cells was performed to analyse the membrane localisation of the generated mutants. The multimerisation pattern of the different sdc4 mutants was analysed using crosslinking upon IL-1 stimulation and subsequent Western blot analysis. Furthermore, fibroblasts lacking sdc4, the IL-1 receptor (IL1-RI) or both were stimulated with IL-1 to unravel the interaction of the IL-1RI and scd4 in IL-1 signaling. Erk1/2 was chosen as readout. <h3>Results</h3> The authors showed that all sdc4 side chain lacking mutants exhibited normal intracellular trafficking into the cell membrane. While wild type sdc4 showed normal multimerisation, the side chain mutants exhibited an impaired sdc4 complex formation, particularly with respect to tetramers. Furthermore, the authors found by our cross-linking experiments that sdc4 undergoes complex formation upon IL-1 stimulation. Analysing downstream signaling, sdc4<sup>-/-</sup> cells showed less IL-1 induced Erk1/2 phosphorylation, while IL-1 induced Erk1/2 phosphorylation was virtually abolished in cells without IL-1RI. The loss of both proteins completely prevented IL-1 dependent Erk1/2 phosphorylation. When comparing the effects of IL-1α and IL-1β on Erk1/2 phosphorylation, the authors found that IL-1β led to faster and more pronounced increase in phosphorylation levels compared to IL-1α. <h3>Conclusion</h3> In conclusion, heparan sulfate side chains are essential for multimerisation of sdc4 and IL-1 stimulation promotes sdc4 complex formation. Additionally, sdc4 seems to be involved in IL-1 signaling and has an additive or even regulatory effect on IL-1 signaling. Therefore, sdc4 complex formation in RA-SF might be an important step in signal transduction during RA disease progression.
Human and Mouse IFN-β Gene Therapy Exhibits Different Anti-tumor Mechanisms in Mouse Models
Authors: Xiao-Qiang Qin, Carla Beckham, Jennifer L. Brown, Matvey Lukashev, James Barsoum
Journal: Molecular Therapy (2001)

Previously, we suggested that local human interferon-β (IFN-β) gene therapy with replication-defective adenoviral vectors can be an effective cancer treatment. Clinical trials to treat cancers with adenovirus expressing the human IFN-β gene (IFNB1) has been planned. As a continued effort to explore the mechanisms of action of human IFN-β gene therapy that can occur in the clinical setting, we tested mouse IFN-β gene therapy in human xenograft tumors in both ex vivo and in vivo models. Delivery of the mouse IFN-β gene (Ifnb) caused tumor inhibition; this effect was dependent on the indirect anti-tumor activities of IFN-β, notably a stimulation of natural killer cells. IFN-β does not show cross-species activity in its anti-proliferative effect and mouse IFN-β does not cause as significant an anti-proliferative effect on mouse tumor cells as human IFN-β causes on human tumor cells. Therefore, we believe that mouse models using either human IFN-β or mouse IFN-β gene transfer do not capture all aspects of the action of adenovirus-mediated human IFN-β gene therapy that may be present in the clinical setting. Due to its multiple mechanisms of action, human IFN-β gene therapy may be effective in treating human cancers that are either sensitive or resistant to the direct anti-proliferative effect of IFN-β.
Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12
Authors: Burkhard Becher, Brigit G. Durell, Randolph J. Noelle
Journal: Journal of Clinical Investigation (2002)

IL-12 is considered a critical proinflammatory cytokine for autoimmune diseases such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-12 is a heterodimer composed of a p35 subunit and a common p40 subunit shared by other cytokines. Both IL-12 p40(-/-) and p35(-/-) mice fail to produce IL-12 p70 heterodimer. However, in contrast to p40(-/-) mice, p35(-/-) mice are highly susceptible to the induction of EAE, establishing that IL-12 p70 is not essential for the development of EAE. When compared with wild-type mice, both p40(-/-) and p35(-/-) mice show deficiencies in primary IFN-gamma responses by lymph node cells. Expression profiling of the inflamed CNS revealed that Th2 cytokines such as IL-4 and IL-10 are upregulated in p35(-/-) mice, whereas LT-alpha and TNF-alpha levels are reduced. These studies show that a molecule other than IL-12 p70, which uses the p40 subunit, fulfills the functions previously attributed to IL-12 with regard to the development and pathogenesis of this autoimmune disease.