tbuckley/cabot-search huggingface dataset:
Matrix Metalloproteinase-12 Expression Correlates with Local Recurrence and Metastatic Disease in Non–Small Cell Lung Cancer Patients
Authors: Hans-Stefan Hofmann, Gesine Hansen, Günther Richter, Christiane Taege, Andreas Simm, Rolf-Edgar Silber, Stefan Burdach
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Non–small cell lung cancer (NSCLC) is a very common and aggressive malignancy. Survival after resection of tumor is especially determined by the occurrence of distant metastasis. Matrix metalloproteinases (MMP) support this metastatic process by degradation of the extracellular matrix. Experimental Design: We used DNA microarray technology to examine the expression of 22 MMPs in 89 surgically treated NSCLC patients. Validation of microarray results was done using reverse transcription-PCR and immunohistology. Results: MMP-1, MMP-9, and MMP-12 expression was significantly increased in tumors versus corresponding lung tissues. MMP-12 expression significantly correlated with local recurrence and metastatic disease. Multivariate Cox regression analysis revealed MMP-12 expression as an independent prognostic factor for tumor relapse–free interval. Gene expression analysis of 158 healthy tissues from 32 different organs revealed no MMP-12 expression in these organs and immunohistology identified MMP-12 protein in NSCLC only in tumor cells. Conclusions: MMP-12 might be not only a prognostic marker, but also a valuable therapeutic target.
Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the genome by association with GATA3
Authors: Seth Frietze, Rui Wang, Lijing Yao, Yu Gyoung Tak, Zhenqing Ye, Malaina Gaddis, Heather Witt, Peggy J Farnham, Victor X Jin
Journal: Genome biology (2012)

Abstract Background The TCF7L2 transcription factor is linked to a variety of human diseases, including type 2 diabetes and cancer. One mechanism by which TCF7L2 could influence expression of genes involved in diverse diseases is by binding to distinct regulatory regions in different tissues. To test this hypothesis, we performed ChIP-seq for TCF7L2 in six human cell lines. Results We identified 116,000 non-redundant TCF7L2 binding sites, with only 1,864 sites common to the six cell lines. Using ChIP-seq, we showed that many genomic regions that are marked by both H3K4me1 and H3K27Ac are also bound by TCF7L2, suggesting that TCF7L2 plays a critical role in enhancer activity. Bioinformatic analysis of the cell type-specific TCF7L2 binding sites revealed enrichment for multiple transcription factors, including HNF4alpha and FOXA2 motifs in HepG2 cells and the GATA3 motif in MCF7 cells. ChIP-seq analysis revealed that TCF7L2 co-localizes with HNF4alpha and FOXA2 in HepG2 cells and with GATA3 in MCF7 cells. Interestingly, in MCF7 cells the TCF7L2 motif is enriched in most TCF7L2 sites but is not enriched in the sites bound by both GATA3 and TCF7L2. This analysis suggested that GATA3 might tether TCF7L2 to the genome at these sites. To test this hypothesis, we depleted GATA3 in MCF7 cells and showed that TCF7L2 binding was lost at a subset of sites. RNA-seq analysis suggested that TCF7L2 represses transcription when tethered to the genome via GATA3. Conclusions Our studies demonstrate a novel relationship between GATA3 and TCF7L2, and reveal important insights into TCF7L2-mediated gene regulation.
Endoscopic Mucosal Impedance Measurements Correlate With Eosinophilia and Dilation of Intercellular Spaces in Patients With Eosinophilic Esophagitis
Authors: David A. Katzka, Karthik Ravi, Debra M. Geno, Thomas C. Smyrk, Prasad G. Iyer, Jeffrey A. Alexander, Jerry E. Mabary, Michael Camilleri, Michael F. Vaezi
Journal: Clinical Gastroenterology and Hepatology (2015)
Fish consumption and early atherosclerosis in middle-aged men
Authors: Yasuyuki Nakamura, Yoshiki Ueno, Shinji Tamaki, Takashi Kadowaki, Tomonori Okamura, Yoshikuni Kita, Naomi Miyamatsu, Akira Sekikawa, Tomoko Takamiya, Aiman El-Saed, Kim Sutton-Tyrrell, Hirotsugu Ueshima
Journal: Metabolism (2007)
Reduced intensity conditioning before allografting: moderate enthusiasm may be more appropriate
Authors: U. Schuler
Journal: European Respiratory Journal (2004)

Since the first clinical series of allogeneic bone marrow transplants were reported, the procedure has been associated with a considerable amount of pulmonary complications, among many other problems. Over the last three decades, huge efforts have been devoted to the avoidance and the effective treatment of these complications. In the past, numerous patients did not undergo transplantation, either because they were considered too ill or too old to tolerate these procedure-related side-effects. In this issue of the European Respiratory Journal (ERJ) , Nusair et al. 1 from Jerusalem report on their experience with pulmonary complications as observed after transplants with “nonmyeloablative” conditioning.

Stem cell transplantation (SCT) can be divided into three components: the conditioning therapy (chemotherapy with/without irradiation), the source and composition of the graft, and the post-transplant immunosuppression. Modifications of all three components may contribute to the profile of efficacy and toxicity of the procedure. The group from the Hadassah University Hospital in Jerusalem was among the first to develop a procedure that tried to minimise the toxicity of the preparative regimen and relied more on the graft- versus -leukaemia (GVL) effect of the transplanted allogeneic immune system 2. Numerous other centres then followed and this has resulted …
Correlative electrophysiological and anatomical studies concerning the site of origin of escape rhythm during complete atrioventricular block in the dog.
Authors: T N James, J H Isobe, F Urthaler
Journal: Circulation Research (1979)

Complete heart block was produced in eight dogs by the selective perfusion of physostigmine or neostigm into the atrioventricular (AV) node artery. A characteristic escape AV junctional rhythm emerged in each dog. After reversal of the cholinesterase paralysis with atropine, in each dog partial heart block was produced by an incision into the AV nodal region. In three of these eight dogs, a second incision placed slightly more anteriorly produced complete AV block which was followed by the emergence of an escape AV junctional rhythm similar to the one produced pharmacologically. Hearts of these three dogs were examined histologically with serial sections to determine the exact location of the incisions and their relationship to the AV node and His bundle. In each dog the incision that produced complete heart block passed directly through the junction of AV node with His bundle. In this region previous studies had demonstrated numerous P cells, which are thought to be the site of origin of normal cardiac automaticity. In each of the three hearts there were abundant P cells in continuity with the His bundle distal to the cut producing heart block. Significance of these findings is discussed relative to the locus of action of acetylcholine within the AV junction, the site of origin of AV junctional rhythm, and sme aspects of the experimental and therapeutic production of heart block.
A successfully treated case of mycetoma due to Nocardia veterana
Authors: M. Kashima, R. Kano, Y. Mikami, H. Takahama, M. Ito, A. Hasegawa, M. Mizoguchi
Journal: British Journal of Dermatology (2005)

We report a successfully treated case of mycetoma from which an unusual Nocardia species was isolated. The isolate was identified as N. veterana by biochemical characterization and 16S ribosomal RNA gene sequencing, and it has not been previously reported as a causative agent of human mycetomas. Treatment with various antibiotics over 6 years and surgical resection failed to cure the disease. However, the combination of intravenous imipenem/cilastatin and amikacin along with oral clarithromycin and minocycline proved very effective in this case. This is the first case report of mycetoma due to N. veterana in a clinical setting.
Comparative Preclinical Pharmacokinetic and Metabolic Studies of the Combretastatin Prodrugs Combretastatin A4 Phosphate and A1 Phosphate
Authors: Ian G. Kirwan, Paul M. Loadman, David J. Swaine, D. Alan Anthoney, George R. Pettit, John W. Lippert, Steve D. Shnyder, Patricia A. Cooper, Mike C. Bibby
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Combretastatin A4 phosphate (CA4P) and its structural analog, combretastatin A1 phosphate (CA1P), are soluble prodrugs capable of interacting with tubulin and causing rapid vascular shutdown within tumors. CA4P has completed Phase I clinical trials, but recent preclinical studies have shown that CA1P displays a greater antitumor effect than the combretastatin A4 (CA4) analog at equal doses. The aim of this study, therefore, is to compare pharmacokinetics and metabolism of the two compounds to determine whether pharmacokinetics plays a role in their differential activity. Experimental Design: NMRI mice bearing MAC29 tumors received injection with either CA4P or CA1P at a therapeutic dose of 150 mg·kg−1, and profiles of both compounds and their metabolites analyzed by a sensitive and specific liquid chromatography/mass spectroscopy method. Results: The metabolic profile of both compounds is complex, with up to 14 metabolites being detected for combretastatin A1 (CA1) in the plasma. Many of these metabolites have been identified by liquid chromatography/mass spectroscopy. Initial studies, however, focused on the active components CA4 and CA1, where plasma and tumor areas under the curve were 18.4 and 60.1 μg·h·ml−1 for CA4, and 10.4 and 13.1 μg·h·ml−1 for CA1, respectively. In vitro metabolic comparisons of the two compounds strongly suggest that CA1 is metabolized to a more reactive species than the CA4. Conclusions: Although in vitro studies suggest that variable rates of tumor-specific prodrug dephosphorylation may explain these differences in pharmacokinetics profiles, the improved antitumor activity and altered pharmacokinetic profile of CA1 may be due to the formation of a more reactive metabolite.
Major Histocompatibility Complex Class I–Recognizing Receptors Are Disease Risk Genes in Rheumatoid Arthritis
Authors: Jeng-Hsien Yen, Brenda E. Moore, Takako Nakajima, Dirk Scholl, Daniel J. Schaid, Cornelia M. Weyand, Jörg J. Goronzy
Journal: The Journal of Experimental Medicine (2001)

Rheumatoid arthritis (RA) is a heterogeneous syndrome of which a subset of patients develops vascular inflammation. The genetic determinants that confer risk for rheumatoid vasculitis are not known, but patients with vascular complications are known to have an expansion of CD4+CD28null T cells, a cell population potentially involved in endothelial damage. CD4+CD28null T cell clones isolated from RA patients with vasculitis were found to express killer cell immunoglobulin–like receptors (KIRs) with the stimulatory KIR2DS2 often present in the absence of opposing inhibitory receptors with related specificities. To test the hypothesis that the KIR2DS2 gene is involved in the development of vasculitis, association studies were performed. The KIR2DS2 gene was significantly enriched among patients with rheumatoid vasculitis compared with normal individuals (odds ratio 5.56, P = 0.001) and patients with RA but no vasculitis (odds ratio 7.96, P = 0.001). Also, the distribution of human histocompatibility leukocyte antigen (HLA)-C, the putative ligand for KIRs, was significantly different in patients with rheumatoid vasculitis in comparison with the control populations. These data suggest that HLA class I–recognizing receptors and HLA class I genes are genetic risk determinants that modulate the pattern of RA expression. Specifically, KIR2DS2 in conjunction with the appropriate HLA-C ligand may have a role in vascular damage by regulating CD4+CD28null T cells.
Is angiotensin II a proliferative factor of cardiac fibroblasts?
Authors: F Bouzegrhane
Journal: Cardiovascular Research (2002)

Angiotensin II has been implicated as an important factor in cardiac remodeling, particularly in the development of pathological left ventricular hypertrophy. It is generally assumed that angiotensin II is able to alter the phenotype of cardiac myocytes and fibroblasts, and several experiments have suggested that this peptide can particularly affect the proliferation of cardiac fibroblasts. However, a review of the published results indicates that there is no evidence that angiotensin II can directly trigger mitogenesis through activation of the cyclin-dependent pathway. The observed proliferative effect might well be caused by stimulation of the synthesis of growth or inflammatory substances like platelet-derived growth factor and cytokines, by integrin activation due to secreted extracellular matrix proteins, or by a combination of these mechanisms. Angiotensin II thus appears to differentiate cardiac fibroblasts into a growth substance-secreting phenotype.
The risk of cardiovascular disease in systemic sclerosis: a population-based cohort study
Authors: Ada Man, Yanyan Zhu, Yuqing Zhang, Maureen Dubreuil, Young Hee Rho, Christine Peloquin, Robert W Simms, Hyon K Choi
Journal: Annals of the Rheumatic Diseases (2012)

Objectives To evaluate the risk of incident myocardial infarction (MI), stroke and peripheral vascular disease (PVD) in individuals with systemic sclerosis (SSc) in a general population context. Methods We conducted a cohort study using a UK primary care database containing records from 1986 to 2011. SSc diagnoses, outcomes and cardiovascular risk factors were identified from electronic medical records. We conducted two cohort analyses: (1) MI and stroke, and (2) PVD, excluding individuals with prevalent disease at baseline for each analysis. We estimated HRs comparing SSc with age-, sex- and entry time-matched comparison cohorts, adjusting for potential cardiovascular risk factors. Results Among 865 individuals with SSc (85.8% women, mean age 58.7 years), the incidence rates (IRs) of MI and stroke were 4.4 and 4.8 per 1000 person-years (PY), versus 2.5 and 2.5 per 1000 PY in the comparison cohort. The corresponding adjusted HRs were 1.80 (95% CI 1.07 to 3.05) for MI and 2.61 (95% CI 1.54 to 4.44) for stroke. Among 858 individuals with SSc (85.3% female, mean age 58.9 years), the IR of PVD was 7.6 per 1000 PY versus 1.9 per 1000 PY in the comparison cohort, with an adjusted HR of 4.35 (95% CI 2.74 to 6.93). Conclusions These findings provide the first general population-based evidence that SSc is associated with an increased risk of developing MI, stroke and PVD. Further insight into disease mechanisms, as well as how disease subtype, organ involvement and medication use may alter these increased risks, is needed.
Psychological disturbance in atopic eczema: the extent of the problem in school‐aged children
Authors: C.M. ABSOLON, D. COTTRELL, S.M. ELDRIDGE, M.T. GLOVER
Journal: British Journal of Dermatology (1997)

Journal Article Psychological disturbance in atopic eczema: the extent of the problem in school‐aged children Get access C.M. ABSOLON, C.M. ABSOLON Department of Child Psychiatry, The Royal London Hospital, London, U.K., Search for other works by this author on: Oxford Academic Google Scholar D. COTTRELL, D. COTTRELL Department of Child Psychiatry, University of Leeds, U.K., Search for other works by this author on: Oxford Academic Google Scholar S.M. ELDRIDGE, S.M. ELDRIDGE Department of Epidemiology and Medical Statistics, Queen Mary and Westfield College, London, U.K., Search for other works by this author on: Oxford Academic Google Scholar M.T. GLOVER M.T. GLOVER Department of Dermatology, Newham General Hospital and the Royal London Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 2, 1 August 1997, Pages 241–245, https://doi.org/10.1046/j.1365-2133.1997.18121896.x Published: 01 August 1997
Acute graft versus host disease after orthotopic liver transplantation
Authors: Inga Mandac Rogulj, Joachim Deeg, Stephanie J Lee
Journal: Journal of Hematology & Oncology (2012)

Abstract Graft versus host disease (GVHD) is an uncommon complication after orthotopic liver transplantation (OLT) with an incidence of 0.1–2%, but an 80–100% mortality rate. Patients can present with skin rashes, diarrhea, and bone marrow aplasia between two to eight weeks after OLT. Diagnosis of GVHD is made based on clinical and histologic evidence, supported by chimerism studies showing donor HLA alleles in the recipient bone marrow or blood. Several therapeutic approaches have been used for the management of GVHD after OLT including increased immunosuppression, decreased immunosuppression, and cellular therapies. However, success rates have been low, and new approaches are needed.
Diabetes Trends Among American Indians and Alaska Natives: 1990–1998
Authors: Ali H. Mokdad, Barbara A. Bowman, Michael M. Engelgau, Frank Vinicor
Journal: Diabetes Care (2001)

In our recent article on diabetes trends in the U.S. (1), we reported that the prevalence of diagnosed diabetes in U.S. adults increased from 4.9% in 1990 to 6.5% in 1998. For this study, we classified participants into four race-ethnic groups: Caucasian, African-American, Hispanic, and other (1). The “other” category included Asian, Pacific Islander, American Indian (AI), Alaska Native (AN), and other race-ethnic groups specified by the respondents. This classification of “other” was necessary because of the small numbers of participants in each of …
Antithrombogenic endothelial cell defense. Basal characteristics in cultured endothelial cells and modulation by short-term and long-term exposure to isosorbide nitrates.
Authors: F P Berenger, J P Cano, P H Rolland
Journal: Circulation Research (1987)

The antithrombogenic endothelial cell defense (ATECD) describes the properties that enable the endothelium to prevent circulating blood platelets from adhering to, or aggregating on, the vascular wall. ATECD was investigated in an experimental model in which bovine passage 0 cultured endothelial cells (EC) were incubated with aggregating platelets and autologous plasma in a computer-operated aggregometer-like device. A maximal platelet aggregation required 150 X 10(-6) M adenosine diphosphate (ADP) to be present in ECs. A 5-minute coincubation for ECs and platelets was found to be adequate in evaluating the maximal ATECD value. By increasing the EC number in the aggregation suspension, platelet aggregation was progressively inhibited through a sigmoid curve (50% inhibition of aggregation required 2 X 10(4) EC). Pharmacologic modulations of ATECD by isosorbide dinitrate (ISDN) + 2-isosorbide mononitrate (2-ISMN) + 5-isosorbide mononitrate (5-ISMN) were investigated under experimental conditions reflecting either an acute nitrate effect (platelet + control ECs + drug + ADP) or a chronic effect (platelet + 5-day nitrate-treated ECs + ADP). Under acute circumstances, ISDN antiplatelet activities were profoundly magnified by ECs. Aggregation was fully arrested with 5 X 10(-5) M ISDN and an EC number of 2 X 10(4), whereas the same ISDN concentration alone induced 30% inhibition of control aggregation. In contrast, there were no significant changes in platelet aggregation whether incubation was done in the presence or absence of 2-ISMN or 5-ISMN, ISDN metabolites. Long-term exposure of ECs to isosorbide nitrates (ISN) resulted in increased acquired EC changes in ATECD. 5-ISMN was a poor antiplatelet agent but was capable of counteracting ISDN effects on ATECD.(ABSTRACT TRUNCATED AT 250 WORDS)
Sudden Cardiac Arrest and Death Following Application of Shocks From a TASER Electronic Control Device
Authors: Douglas P. Zipes
Journal: Circulation (2012)

The safety of electronic control devices (ECDs) has been questioned. The goal of this study was to analyze in detail cases of loss of consciousness associated with ECD deployment.Eight cases of TASER X26 ECD-induced loss of consciousness were studied. In each instance, when available, police, medical, and emergency response records, ECD dataport interrogation, automated external defibrillator information, ECG strips, depositions, and autopsy results were analyzed. First recorded rhythms were ventricular tachycardia/fibrillation in 6 cases and asystole (after ≈ 30 minutes of nonresponsiveness) in 1 case. An external defibrillator reported a shockable rhythm in 1 case, but no recording was made. This report offers evidence detailing the mechanism by which an ECD can produce transthoracic stimulation resulting in cardiac electrical capture and ventricular arrhythmias leading to cardiac arrest.ECD stimulation can cause cardiac electrical capture and provoke cardiac arrest resulting from ventricular tachycardia/ventricular fibrillation. After prolonged ventricular tachycardia/ventricular fibrillation without resuscitation, asystole develops.
Motor neurone disease: can we do better? A study of 42 patients.
Authors: P G Newrick, R Langton-Hewer
Journal: BMJ (1984)

A feeling that patients with motor neurone disease were not always well managed prompted a study of the symptoms, functional levels, and use of aids in a group of 42 patients. Pain, falls, constipation, and swelling of the legs emerged as the major symptomatic problems. At the time of assessment two thirds of the patients appeared to be in need of aids which had not been provided. Disturbance of sleep secondary to positional nocturnal discomfort caused much distress to both the patient and spouse; and this might be eased by the use of an electric turning bed. Over half the patients said that they disliked attending neurology outpatient clinics. Criticism centred on poor transport arrangements, lack of information about the control of symptoms, and unsatisfactory help from junior staff. A key worker should be identified as part of a new strategy for managing these patients.
The Relationship of Pathogenetic Mechanisms to Treatment in Patients with Pain
Authors: Alec Ramsay
Journal: Psychotherapy and Psychosomatics (1984)

Pain is the somatic symptom par excellence, legitimizing more than any other the sick role and illness behavior. The functions and implications of pain are clearest in situations of acute illness or injury or in chronic, organically based conditions in which actual or threatened tissue damage is signaled by its report. Much greater complexity is found in a variety of clinical presentations (conversion hysteria, hypochondriasis, chronic pain syndromes, Briquet's syndrome, Munchausen's syndrome) in which pain may form part or all of the clinical picture. In such conditions the relationship of the patient's report of pain to other phenomena (tissue damage, physiopathology, perceptual and cognitive styles, personality type, individual and family psychodynamics, anxiety, depression, behavioral patterns, social and economic factors, cultural influences) is important in elucidating pathogenetic mechanisms of which several may be operating in any one case. Awareness of the existence and interaction of these mechanisms facilitates the development and integration of treatment approaches.
An Electric Device for Instantaneous and Continuous Computation of Aortic Blood Velocity
Authors: DONALD L. FRY, FRANK W. NOBLE, ALEXANDER J. MALLOS
Journal: Circulation Research (1957)

An electric device is described which computes the instantaneous aortic blood velocity from the pressure difference between two points along the aorta. The pressure difference was obtained from a specially designed double lumen catheter attached to a differential pressure gage. The aortic blood velocity curves obtained from 20 dogs compare closely with most of those appearing in the literature.
Visual Acuity and Intraocular Pressure after Descemet's Stripping Endothelial Keratoplasty in Eyes with and without Preexisting Glaucoma
Authors: Thasarat S. Vajaranant, Marianne O. Price, Francis W. Price, Weihua Gao, Jacob T. Wilensky, Deepak P. Edward
Journal: Ophthalmology (2009)
1001-16 Bipolar radiofrequency isolation of the pulmonary veins for treatment of atrial fibrillation
Authors: A.Marc Gillinov, Patrick M McCarthy, Eugene H Blackstone, Gosta Pettersson, Royce Calhoun, Jennifer E Cummings, Andrea Natale, Nassir Marrouche
Journal: Journal of the American College of Cardiology (2004)