tbuckley/cabot-search huggingface dataset:
Suramin: Here to Stay!?
Authors: H. I. Scher
Journal: JNCI Journal of the National Cancer Institute (1993)

Suramin was one of the first chemotherapeutic agents developed with efficacy against a parasitic disease.Originally synthesized in the early 1900s, the drug was extensively used in the 1920s and 1930s.Clinical use waned until in vitro studies showed that suramin could inhibit reverse transcriptase and antagonize the binding of a number of polypeptide growth factor ligands (platelet-derived growth factor, basic fibroblast growth factor, transforming growth factor-p, and epidermal growth factor) with their receptors.Demonstration of antitumor activity in hormone-refractory prostatic cancer, a disease for which there is no effective therapy, generated even more interest in the compound.The highly charged nature of suramin results in a significant degree of protein binding, a factor that may contribute to its diverse biologic actions.Suramin not only affects interactions between growth factor and growth factor receptors-it can also induce differentiation (7) and inhibit mitochondrial function (2), adrenal steroidogenesis (3), protein kinase C (4), glycolysis (5), membrane-associated ion pumps (6), and the metastatic process through an effect on cell motility (7).The effects are nonspecific, and currently, it is unclear whether the tumoricidal action is the result of the extracellular or the intracellular effects of the compound.Suramin was evaluated in prostatic cancer on the basis of the inhibitory effects on growth-factor-induced mitogenesis and proliferation and antitumor activity against humanderived prostatic cancer cell lines in vitro and in vivo (8).The initial report by Myers et al. (8) in 1989 showed measurable disease response in four of eight patients and prostate-specific antigen (PSA) declines in seven of 11 patients treated.In that trial, suramin was administered by continuous infusion until a target concentration of 280-300 Hg/mL was reached.Due to the effects on the adrenal gland, all patients received hydrocortisone replacement from the start of treatment.While the reported therapeutic efficacy stimulated intense interest, the drug also achieved notoriety for its seemingly prohibitive toxic effects profile.The situation was not dissimilar to that observed with the earliest use of cisplatin.Some toxic effects, such as the skin rash, are idiosyncratic (9), while others, such as the vortex keratopathy and coagulopathy, are related to the inhibitory effects of suramin on glycosaminoglycan synthesis (10,11).Other side effects include renal insufficiency, adrenal insufficiency, throm-
Diagnostic Tests for Lyme Disease
Authors: Henry M. Feder
Journal: JAMA (1990)

<h3>To the Editor.—</h3> In their recent study, Schwartz and colleagues<sup>1</sup>emphasized the variability of results using standard antibody tests for<i>Borrelia burgdorferi</i>, the agent of Lyme disease. In addition to the standard antibody tests there are experimental Lyme disease tests that may give misleading results. <h3>Report of a Case.—</h3> A 36-year-old woman was hospitalized because of fever and neutropenia that occurred following cefotaxime therapy for presumed Lyme disease. In 1988 the patient developed diffuse muscle and joint pains. Findings from physical examination and laboratory studies, including an enzyme-linked immunosorbent assay (ELISA) for antibodies to<i>B burgdorferi</i>, were negative. The patient lived in an area endemic for Lyme disease and believed that her symptoms were due to Lyme disease. An empiric 21-day course of penicillin V (500 mg four times daily) was prescribed. Her symptoms continued, and she was referred to a rheumatologist, who found no objective finding consistent with
Tumour suppressor genes.
Authors: R. Vile
Journal: BMJ (1989)

Key points * The loss of tumour suppressor genes may lead to cancer * The normal function of the suppressor genes may be to override proliferative signals and allow cell differentiation * In familial cancers one copy of the suppressor gene may be lost from the chromosome and a second by mutation * In sporadic cancers both copies of the same suppressor genes may be lost by mutation * An understanding of tumour suppressor genes may lead to new methods of screening and even treatment 1335
Moyamoya Disease in Twins
Authors: YUSUF DUMAN, AYŜEGÜL DIRLIK, ZEYNEP BURAK, SARENUR TÜTÜNCÜ
Journal: Clinical Nuclear Medicine (1995)

Tc-99m HMPAO SPECT was used to evaluate regional blood flow in one monozygotic twin who had anglographically proven moyamoya disease. Focal and global reduced regional cerebral perfusion were observed in both patients with Tc-99m HMPAO SPECT studies. There was good correlation between the localization and degree of regional cerebral blood flow abnormalities and the severity and stage of clinical symptoms on angiography. These results suggest that Tc-99m HMPAO SPECT is a useful method in the detection of hemodynamic abnormalities in moyamoya disease.
Accumulation of 8-nitroguanine in the liver of patients with chronic hepatitis C
Authors: Shinichiro Horiike, Shosuke Kawanishi, Masahiko Kaito, Ning Ma, Hideaki Tanaka, Naoki Fujita, Motoh Iwasa, Yoshinao Kobayashi, Yusuke Hiraku, Shinji Oikawa, Mariko Murata, Jinyan Wang, Reiji Semba, Shozo Watanabe, Yukihiko Adachi
Journal: Journal of Hepatology (2005)
TCT-471 Relation of Stent Thrombosis to Interruption of Dual Antiplatelet Therapy After Resolute Zotarolimus-eluting Stent Implantation
Authors: Deepak L. Bhatt, Sigmund Silber, Stephan Windecker, Sandeep Brar, Minglei Liu, Xiaohua Chen, Ajay J. Kirtane
Journal: Journal of the American College of Cardiology (2013)
The Toxicity of D-Penicillamine in Systemic Sclerosis
Authors: VIRGINIA D. STEEN
Journal: Annals of Internal Medicine (1986)

We studied D penicillamine toxicity in 259 patients with systemic sclerosis treated since 1972. The average daily dose of 635 mg was given for a mean of 1.8 years. Of patients with systemic sclerosis, 47% had side effects from D-penicillamine treatment, similar to the 56% of 807 patients with rheumatoid arthritis in seven separate series. Individual manifestations of toxicity included rash, proteinuria, gastrointestinal symptoms, dysgeusia, oral ulcers, thrombocytopenia, and neutropenia. Four episodes each of myasthenia gravis and pemphigus occurred in our patients; both were reported rarely in patients with rheumatoid arthritis. Adverse effects occurred more frequently after rapid increases in dosage. Treatment had to be discontinued due to toxicity in 29% of patients with systemic sclerosis and in 33% of those with rheumatoid arthritis. Although toxic, with a high frequency of adverse effects, D-penicillamine can be used safely in the treatment of systemic sclerosis. Pemphigus and myasthenia gravis may occur more frequently with therapy for systemic sclerosis than with that for rheumatoid arthritis.
Underestimating Medical Therapy for Coronary Disease . . . Again
Authors: James C. Fang
Journal: New England Journal of Medicine (2011)

The question of how best to treat patients with multivessel coronary artery disease and left ventricular dysfunction has challenged physicians for years. Although most clinicians are comfortable recommending revascularization when there is angina, extensive coronary disease, and a left ventricular ejection fraction of more than 35%,13 the benefits of such a strategy are less clear when the ejection fraction is substantially impaired.The evidence base for the benefits of revascularization is even weaker when angina is not present in patients with ischemic cardiomyopathy. In such a situation, myocardial viability and hibernation (i.e., chronically hypoperfused myocardium resulting in a hypocontractile . . .
S14 Histone deacetylase activity is reduced in COPD subjects during rhinovirus induced exacerbations
Authors: J. I. M. Footitt, P. Mallia, M. B. Trujillo-Torralbo, A. Durham, I. M. Adcock, S. L. Johnston
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Histone deacetylase (HDAC) enzymes have a role in suppressing inflammatory gene transcription. There is evidence for reduced HDAC activity in COPD which correlates with the severity of airflow obstruction. Increased inflammation found during exacerbations of COPD may result from a reduction in HDAC activity but this has not been studied in virus induced exacerbations. We sought to investigate HDAC activity following rhinovirus infection in an experimental model of COPD exacerbations. <h3>Methods</h3> Experimental rhinovirus challenge was performed in GOLD stage II COPD subjects and non-obstructed control smokers and non-smokers. Rhinovirus infection was confirmed with quantitative PCR performed on nasal lavage and sputum samples collected at baseline and days 3, 5, 9, 12, 15, 21 and 42 post virus inoculation. Sputum macrophages were isolated by adhesion and HDAC2 isoenzyme immunoprecipitated, prior to performing a HDAC activity assay. <h3>Results</h3> 11 non-smokers (NS), 10 smokers (Smk) and 9 COPD subjects were recruited. The mean (SEM) % predicted baseline FEV<sub>1</sub> was 103 (4), 98 (4) and 69 (2)% for NS, Smk and COPD respectively. At baseline there was no difference in HDAC2 activity between the three study groups, the geometric mean (95% CI) activity was NS 22.39 (12.45 to 40.25); Smk 22.91 (18.28 to 28.71) and COPD 48.98 (26.04 to 92.13) (p=0.095). Following rhinovirus infection, in NS HDAC2 activity increased, in Smk it remained largely unchanged and there was a fall from baseline levels in COPD subjects at all time points, Abstract S14 figure 1. <h3>Conclusions</h3> HDAC2 activity was not reduced in stable COPD subjects compared to controls. This may reflect the mild disease state of the study population. During a rhinovirus induced exacerbation HDAC2 activity fell in COPD subjects, this represents a potential mechanism of excessive inflammation. The same pattern is not seen in control subjects.
The embodied bases of supernatural concepts
Authors: Brian R. Cornwell, Aron K. Barbey, W. Kyle Simmons
Journal: Behavioral and Brain Sciences (2004)

According to embodied cognition theory, our physical embodiment influences how we conceptualize entities, whether natural or supernatural. In serving central explanatory roles, supernatural entities (e.g., God) are represented implicitly as having unordinary properties that nevertheless do not violate our sensorimotor interactions with the physical world. We conjecture that other supernatural entities are similarly represented in explanatory contexts.
Pseudomelanosis of the stomach
Authors: R. Kibria, C. Barde
Journal: Endoscopy (2010)

A 79-year-old woman was seen in consultation for postprandial epigastric pain and early satiety of 2 months’ duration, along with weight loss of 4.5 kg (10 lb). Her history included depression, hypertension, congestive heart failure, and iron deficiency anemia without overt bleeding. Medications included bupropion, escitalopram oxalate, ferrous sulfate, carvedilol, and furosemide. Seven months earlier, an upper and lower endoscopy for the workup of iron deficiency anemia was unremarkable. Upper endoscopy now revealed dark pigmentation of the pyloric antral mucosa ([Fig. 1]).
The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma
Authors: R García-Sanz, J R González-Porras, J M Hernández, M Polo-Zarzuela, A Sureda, C Barrenetxea, L Palomera, R López, C Grande-García, A Alegre, M Vargas-Pabón, O N Gutiérrez, J A Rodríguez, J F San Miguel
Journal: Leukemia (2004)
Abstract 3777: Low physiological fluid shear exposure induces metastatic potential of chondrosarcoma cells via MMP-12 activation.
Authors: Shih-Hsun Chen, Pu Wang, Wei-Chien Hung, Konstantinos Konstantopoulos
Journal: Cancer Research (2013)

Abstract Interstitial flow in and around tumor tissue affects the mechanical microenvironment to modulate tumor cell metastasis. We investigated the roles of flow-induced shear stress in modulating chondrosarcoma cell metastatic potential such as cell invasiveness and motility, and the underlying mechanisms. Using human chondrosarcoma cell lines as a model system, we demonstrated that low fluid shear (2 dyn/cm2), but not high fluid shear (20 dyn/cm2), exposure for 48 h remarkably induced MMP-12 mRNA by ∼35-fold and significantly triggered it proteolytic activity among all MMP members. The molecular basis of the shear effect was further analyzed, and our data revealed that low fluid shear stress induces the rapid synthesis of VEGF-B, VEGF-D and IGF-2, which in turn transactivates MMP-12 expression via PI3K and p38 MAPK-dependent pathways. Furthermore, highly induced MMP-12 markedly enhanced chondrosarcoma cell invasion and motility by using chemtaxis transwell chambers in conjunction with time-lapse micro-channel assays. Collectively, our data suggest that the induction of IGF-2, VEGF-B, and VEGF-D under low fluid shear, which in turn upregulates MMP-12 via PI3K and p38 MAPK signaling pathways, leading to the enhanced invasive and migratory capabilities of chondrosarcoma cells. Our findings provide insights into the mechanism by which shear stress induces chondrosarcoma metastatic potential and demonstrate the importance of mechanical environments in modulating molecular signaling, gene expression and functions in tumor cells. Citation Format: Shih-Hsun Chen, Pu Wang, Wei-Chien Hung, Konstantinos Konstantopoulos. Low physiological fluid shear exposure induces metastatic potential of chondrosarcoma cells via MMP-12 activation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3777. doi:10.1158/1538-7445.AM2013-3777
Tufts University Medical School Center Explores Genetic Defenses of Bacteria, Cancer Cells
Authors: Andrew A. Skolnick
Journal: JAMA (1993)

RESEARCHERS AT the Center for Adaptation Genetics and Drug Resistance at Tufts University Medical School, Boston, Mass, are out to outfox the defense systems of bacteria and cancer cells. According to its director, Stuart B. Levy, MD, professor of medicine and of molecular biology and microbiology, the newly opened center is unique in being devoted to the study of genes and gene products that are called into play by bacteria and mammalian cells when exposed to growth inhibitory agents and other environmental stresses. The multidisciplinary center currently has 18 researchers with expertise in molecular biology, genetics, nucleic acid and protein biochemistry, membrane transport, pharmacology, physiology, oncology, and infectious diseases. Their efforts are divided into four areas: tetracycline resistance, regulation of multidrug resistance in bacteria, multidrug resistance in cancer cells, and the development of soil bacteria for cleaning up toxic wastes. The alarming increase in the incidence of multidrug-resistant bacteria underscores
Scurvy: A Survey of 53 Cases
Authors: R. B. McMillan, J. C. Inglis
Journal: BMJ (1944)

patients with scurvy-48 males and 5 females-were admitted to medical wards in an Edinburgh municipal general hospital.The annual number of cases, and the percentage they formed of all medical admissions, are shown in Table I.TABLE I Year Cases of Scurvy Nos.all Medical '4 Incidence Year ~~~~~Admissions
Bacterial lipopolysaccharide-induced intestinal microvascular lesions leading to acute diarrhea.
Authors: V I Mathan, G R Penny, M M Mathan, D Rowley
Journal: Journal of Clinical Investigation (1988)

Subcutaneous challenge of mice with lipopolysaccharide (LPS) from gram negative bacteria, produced an intestinal microvascular lesion causing fluid exudation into the lumen of the intestine and diarrhea. The microvascular lesion was characterized by endothelial cell damage and microthrombi in the venules and capillaries of the intestinal lamina propria. Marker organisms, given orally to challenged mice, grew in the exuded fluid and could invade the mucosa. Intravenous transfer of postchallenge plasma produced the lesion in normal mice and absorption of such plasma by Sepharose coupled to LPS-antibody abolished this effect. Instillation of large quantities of LPS into the lumen of the intestine produced scattered microvascular lesions, although none of these animals developed diarrhea. Since a similar microvascular lesion has been described in the rectal mucosal lamina propria of adults with acute diarrhea, it is suggested that LPS-induced vascular damage may be a novel mechanism in the pathogenesis of acute diarrhea.
Non–Small Cell Lung Cancer, Version 6.2015
Authors: David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D’Amico, Todd L. Demmy, Thomas J. Dilling, M. Chris Dobelbower, Ramaswamy Govindan, Frederic W. Grannis, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Lee M. Krug, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo, Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Steven E. Schild, Theresa A. Shapiro, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2015)

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies. These NCCN Guidelines Insights describe the different testing methods currently available for determining whether patients have genetic alterations in the 2 most commonly actionable genetic alterations, notably anaplastic lymphoma kinase (ALK) gene rearrangements and sensitizing epidermal growth factor receptor (EGFR) mutations.
A CASE OF FRACTURED PELVIS COMPLICATED BY LACERATION OF THE FEMORAL VEIN TREATED BY LATERAL VEIN SUTURE
Authors: M. Moritz
Journal: BMJ (1912)

alive to the immense difficulty that there is in many cases -so great as to make a sure diagnosis in some cases im- possible, especially in stout people and in pregnant women.In the majority of instances, however, it is not because a diagnosis has not been made, but rather because, having been made, it has not been acted upon, that so many cases come to the surgeon with complications. SPONTANEOUS REDUCTION OF INTUS-SUSCEPTION.
Lectures on Dentistry in Medical Schools
Authors: Mortimer Lorber
Journal: JAMA (1978)

Although the medical and dental professions have much in common, their knowledge about each other is disparate. Dental schools teach students the essentials of clinical medicine, but the typical medical school does not reciprocate concerning dentistry. I assume that this curriculum omission is based on two assumptions: (1) So much is to be learned in medical school that the mouth and teeth are comparatively unimportant and not worthy of scarce curricular time. (2) The mouth is really not being neglected since dentists handle oral problems. Unfortunately, medical schools usually do not teach students what the dentist can do to diagnose and treat such problems. Therefore, physicians receive their MD degree without having any more knowledge of the scope of modern dentistry than they had when entering medical school as freshmen. To fill this void in the medical curriculum, we requested seven years ago that three lectures on dentistry be given
Self examination of the breast: is it beneficial? Meta-analysis of studies investigating breast self examination and extent of disease in patients with breast cancer.
Authors: D. Hill, V. White, D. Jolley, K. Mapperson
Journal: BMJ (1988)

The question whether the aggregated published research suggests that breast self examination is beneficial was explored in a meta-analysis of 12 studies including a total of 8118 patients with breast cancer that related the practice of breast self examination to regional lymph node state or tumour diameter. Based on the six studies for which data were available, 39% of patients (1115/2852) who reported having done breast self examination at least once before their illness had evidence of cancer in the lymph nodes compared with 50% of women (1348/2713) who had not done the examination. Logistic regression analysis showed this difference to be significant (odds ratio 0.66, confidence interval 0.59 to 0.74). Combining six studies which reported the circumstances of detection disclosed that 42% of women (272/652) who found their tumour while doing breast self examination had evidence of cancer in the nodes compared with 46% of women (871/1901) who found the tumour accidentally; this difference was not significant. Analysis of eight studies which used the diameter of the tumour to indicate the extent of disease tended to confirm the findings on lymph node state, in particular the benefit of premorbid breast self examination. Significantly fewer women who had practised the examination before the illness (56%; 1205/2137) had tumours of 2 cm or more diameter compared with women who had not practised the examination (66%; 1500/2260). The combined odds ratio for that analysis was 0.56, confidence interval 0.38 to 0.81. These findings appear to be good evidence of the benefit of encouraging women to practise self examination of the breasts regularly.
Changes in the acid glycosaminoglycan content of the matrix of ageing human articular cartilage.
Authors: R A Stockwell
Journal: Annals of the Rheumatic Diseases (1970)

Early chemical studies of the glycosaminoglycans of cartilage matrix (Kuhn and Leppelmann, 1958;Kaplan and Meyer, 1959) indicated an increasing content of keratansulphate with maturation and ageing, particularly when considered in relation to the total quantity of mucopolysaccharide.Subse- quently, the general distribution of chondroitin sulphate and keratansulphate within the matrix were demonstrated by histochemical means (Stock- well and Scott, 1965; Scott and Stockwell, 1966).Quantitative evidence was later presented supporting the histochemical results in human articular cartilage (Stockwell and Scott, 1967; Maroudas, Muir and Wingham, 1969).Investigation has now been ex- tended to a larger series of cases; this has revealed the presence, within the superficial zone of adult articular cartilage, of glycosaminoglycan material not observed previously.It is believed that this finding is relevant to the study of ageing and de- generation in synovial joints. Material and methods MATERIALSixty specimens of human femoral condylar cartilage were examined, the ages of the subjects ranging from birth to 78 years.Fifty cases were obtained post mortem and ten at amputation or surgical exploration of the joint.Many joints examined were macroscopically normal. METHODSJoint surfaces were wiped gently with saline-moistened cotton wool before the tissue was excised.Cartilage from 56 cases was examined histochemically.Full-thickness blocks were taken from areas free of niacroscopic lesions.These were fixed in neutral 10 per cent.formalin for 24 hours and 10 jm.frozen sections were cut at -25°C. in a cryostat.Sections were stained using the following techniques.(la) Alcian blue, 8GX 0 05 per cent. in 0 -05M acetate copyright.
Regressions and eye movements: Where and when
Authors: Manuel Perea, Manuel Carreiras
Journal: Behavioral and Brain Sciences (2003)

Reichle et al. argue that the mechanism that determines where to fixate the eyes is controlled mostly by low-level processes. Therefore, unlike other competing models (e.g., the SWIFT model), the E-Z Reader model cannot account for “global” regressions as a result of linguistic difficulties. We argue that the model needs to be extended to account for regressive saccades.